US20190099340A1

US 20190099340A1
( 19) United States

( 12) Patent Application Publication (10 ) Pub .No.: US 2019 /0099340 A1
FIELDS et al. (43) Pub . Date : Apr . 4 , 2019
(54 ) RETINALDEHYDE CONTAINING A61K 8 /37 (2006 . 01)
COMPOSITIONS AND METHODS OF USE A610 19 / 08 ( 2006 .01)
(71) Applicant: RODAN & FIELDS, LLC , San (52 ) CPC
U .S. CI .
.... ......... A61K 8 /34 (2013.01 ); A61K 8 /64
Francisco , CA (US) ( 2013 .01); A61K 8 /891 ( 2013 .01); A61K
2800 / 874 ( 2013 .01) ; A61K 8 /37 ( 2013 .01);
(72 ) Inventors : Kathy Ann FIELDS, San Fransisco , A61Q 19/08 ( 2013 .01); A61K 8/ 24 (2013 .01 )
CA (US) ; Kathryn Pregerson
RODAN , Oakland , CA (US); George
Paul MAJEWSKI, Emeryville , CA (57 ) ABSTRACT
(US); Timothy John FALLA , This disclosure is directed to compositions comprised of
Woodinville , WA (US) ; Robert retinaldehyde, one or more skin conditioning agents, and ,
BIANCHINI, Dana Point, CA (US) optionally , one or more additional retinoids. This disclosure
( 21) Appl. No.: 16 / 148 ,768 is directed . Embodiments are also directed to compositions
comprised of retinaldehyde, one or more peptides, one or
( 22 ) Filed : Oct. 1 , 2018 more skin conditioning agents, one ormore calcium con
taining agents , and , optionally , one or more additional
Related U .S. Application Data retinoids. Embodiments are also directed to compositions
comprised of retinaldehyde , one or more peptides, one or
(60 ) Provisional application No .62/ 565 ,314, filed on Sep . more skin conditioning agents , one or more calcium con
29, 2017 . taining agents, and, optionally, one or more additional
Publication Classification retinoids . Additional embodiments disclose methods for
treating the skin wherein a characteristic of the skin is
(51) Int. Ci. improved , the characteristics include firmness , elasticity ,
A61K 8 /34 ( 2006 . 01) fine lines and wrinkles, skin texture , dullness , dyschromia ,
A61K 8 /64 (2006 .01) skin tone , reduction or elimination of acne, and any com
A61K 8 /891 ( 2006 .01) bination thereof. This disclosure is also directed to kits used
A61K 8 / 24 ( 2006 .01 ) for treating the skin with the compositions described herein .
.....
Patent Application Publication Apr. 4 , 2019 Sheet 1 of 21 US 2019 /0099340 A1
**
*..
14 *
titript:
10 *
*
*
**
*
*
postomuovi**
produkter
.
verse
.
WW
12
FIG . 1
20
16
18
FIG . 2
,
'
.
'
:
.
,
2
.
'
.
'
3A
.
FIG
$ aloos Ouipelo lejupo urcouevo % veow

sit
i
.i'i i
i'. ,
)
91
'
DE
i ,
.ri
2 .2 . 3
FIG . 4A
Sodom
.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'."
OO
20 X
FIG . 4B
Patent Application Publication Apr . 4 , 2019 Sheet 7 of 21 US 2019/0099340 A1
. . . . . . . . . . . . . . . . . . . . .
** **** *** * *** * * **** *** ********* ******** * * * * * ** *** * ****** ****** *** * *
ooo
FIG . 5A
doruotps
ANAS
FIG . 5B
*********************************************************************************************
FIG . 6A
.
.
FIG . 6B
Patent Application Publication Apr. 4 , 2019 Sheet 11 of 21 US 2019/0099340 A1
. .. . . . . . . . .. . . . .
FIG . 7A
FIG . 7B
. , . , , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . , . ,
: :: : : : : : : :: : : : :: : : : : : : : : : :: : : : : :: : :
W * **** *
D er
. . . . . . . . . . . . . . . . . . . . . . . . . .
FIG . 8
, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
-?% 593548;
? % ? ? ??
.. . ... . .. . .. ... ? ? ? ? ? . ? . ? . ?. ?. ? . ????????????? . .. ?? ?? ? : ? . ?? ? . ? . .
????????????????? ?????????????????????????????????????????????
+ + ++ + + + + + + + ++ + + + + + + +
???
+ + + + + + + + ++ + + + + + + + + + + + + + + ++ + + + + + +
?? ??????
++ + + + +
?
FIG . 9
. : : : : : : :: : : :: : : :: : : :: : : :: : : :: : : :: : : :: : : :: :: :: :: : :: :: : :: :: : :: :: : :: :: : :: :: : :: :: : :: :: : :: :: : :: :: : :: :: : : :
................
.. .. . .. .. . . ** *
*
' ' ' ' ' ' '
W ten
. .. pic ..
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
V . . . . . . . . . . .
. ... .
FIG . 10
". . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .'. .'. . '. .'. ."
.. ... ... ... ... ... . ." ' ." ' ." ' . " ' ." ' ." ' . " ' ." . ' ? ? ? ? ? ? ?? ? ? ? ? . . . " . ' . . ' . . ' . . . . . . . . . ?
?
*
?
? ? ?? ????
.' . .' . . . . . . . . . . . . . .' . ? .' . . . . . . . . . . . . . . . . " ????
?
?
?? ??
? ? ? ? ? ? ? ? ?.
?
?
?? ? ? ? ? ? ? ??
? ?
?
??? . . . . . . . . ." ?
* * * * * * * * * * * * * * * * * * ** * * * * * * * * * * * * * *** *
????. . . . . . . . . . . . . . . . . . . . . . . .
???????????????????????????????????????????????????????????????
?? ?
5ig ' ££
. . . .. . .. . . .. . .. . .. . . .. . . .. . .. . . .. . . . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . ..
111111111111111111111111111111111
12
.
FIG
W
FIG
.
13
*
*
*
*
*
*
*
23
14
.
FIG
---- - -- -- - - . -- - . - -- . . ---
iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii
*
*
*
15
.
FIG
:
.
1
1
.
3
.N N N
16
.
FIG
Colorimetric Arbitrary( 8-IL .

US 2019 /0099340 A1 Apr. 4 , 2019
RETINALDEHYDE CONTAINING consisting of firmness, elasticity, fine lines and wrinkles,

COMPOSITIONS AND METHODS OF USE skin texture , dullness , dyschromia , skin tone, reduction or
elimination of acne , and any combination thereof. Embodi
SUMMARY ments herein are also directed to a method of treating skin
comprising: (a ) rolling the skin with a micro - exfoliation
[0001] Embodiments herein are directed to a skin compo tool, wherein the micro - exfoliating tool comprises a handle
sition comprising retinaldehyde, one or more skin condi and a head , the head comprising a roller, a mechanism of
tioning agents, and , optionally , one or more additional mounting the roller to the handle , and one or more needles
retinoids . Embodiments herein are directed to a skin com fixed to the roller; and ( b ) topically applying a composition
position comprising retinaldehyde, one or more skin condi to skin , wherein the composition comprises retinaldehyde ,
tioning agents , one or more calcium containing agents , and , one or more skin conditioning agents, and optionally, one or
optionally , one or more additional retinoids. Embodiments more additional retinoids, one or more peptides and one or
herein are directed to a skin composition comprising reti more calcium containing agents , wherein treating the skin is
naldehyde , one or more peptides , one or more skin condi an improvement in a characteristic of the skin selected from
tioning agents, one ormore calcium containing agents , and, the group consisting of firmness , elasticity , fine lines and
optionally , one or more additional retinoids. In some wrinkles , skin texture , dullness , dyschromia , skin tone ,
embodiments, the optional one or more additional retinoids reduction or elimination of acne, and any combination
is selected from the group consisting of retinyl palmitate , thereof. Embodiments herein are also directed to method of
alitretinoin ( 9 -cis -retinoic acid ), tretinoin (all -trans-retinoic treating skin comprising: (a ) cleansing the skin with a daily
acid ), isotretinoin ( 13 -cis -retinoic acid ), etretinate , acitretin , cleansing mask ; (b ) topically applying a toner to skin ; and
adapalene , bexarotene , tazarotene, hydroxypinacolone ret ( c ) topically applying a composition to skin , wherein the
composition comprises retinaldehyde, one or more skin
inoate (HPR ), retinoid ester , retinoate , 2 -( nicotinamido ) conditioning agents , and , optionally , one ormore additional
ethylretinoate (NEAR - 1), and derivatives and combinations retinoids, one or more peptides , one or more calcium con
thereof. In some embodiments, the one or more skin con taining agents , wherein treating the skin is an improvement
ditioning agents is selected from the group consisting of in a characteristic of the skin selected from the group
cyclopentasiloxane, dimethicone , polysilicone- 11, ethyl consisting of firmness, elasticity, fine lines and wrinkles ,
hexyl hydroxystearate , C12 - 15 alkyl benzoate , bis -ethyl skin texture , dullness, dyschromia , skin tone, reduction or
hexyl hydroxydimethoxy benzylmalonate, ethoxydiglycol, elimination of acne , and any combination thereof.
hyaluronic acid , alpha hydroxyl acids , glycolic acid , lactic [0003] Embodiments herein are also directed to a kit
acid , ascorbic acid , polyhydroxy acids, gluconolactone, lac comprising : a micro - exfoliation tool ; a topical skin compo
tobionic acid , beta hydroxyl acid , peat extract, glycine, cetyl sition comprising: retinaldehyde , one or more skin condi
alcohol, stearyl alcohol, and derivatives and combinations tioning agents , and optionally , one or more additional ret
thereof. In some embodiments, the optional one or more inoids; and instructions for use . Embodiments herein are
peptides is selected from the group consisting of palmitoyl also directed to a kit comprising: a micro - exfoliation tool; a
hexapeptide - 14 , oligopeptide- 10 , myristoyl pentapeptide- 8 , topical skin composition comprising : retinaldehyde, one or
myristoyl tetrapeptide- 8 , sericin , silk protein , collagen , kera more skin conditioning agents , and one or more calcium
tin , amino acids, hexapeptide -21, palmitoyl oligopeptide , containing agents, and optionally , one or more additional
palmitoyl tetrapeptide- 7 , tetrapeptide - 16 , polyacrylate- 13 , retinoids; and instructions for use . Embodiments herein are
polyisobutene , polysorbate -20 , betaine, milk solids, rice also directed to a kit comprising : a micro - exfoliation tool; a
peptides, and derivatives and combinations thereof. In some topical skin composition comprising: retinaldehyde, one or
embodiments, the optional one or more calcium containing more peptides, one or more skin conditioning agents , and
agents is selected from the group consisting of hydroxyapa one or more calcium containing agents and optionally , one
tite , calcium lactate, calcium chloride , calcium carbonate , or more additional retinoids; and instructions for use.
calcium phosphate , calcium pyrophosphate , calcium sulfate , [0004 ] Embodiments herein are also directed to a kit
dicalcium phosphate, dicalcium phosphate dehydrate , trical comprising : a daily cleansing mask ; a topical toner ; a topical
cium phosphate, calcium undecylenate, and derivatives and skin composition comprising : retinaldehyde, one or more
combinations thereof. skin conditioning agents , and, optionally , one or more addi
[0002 ] Embodiments herein are also directed to a method tional retinoids; and instructions for use . Embodiments
of treating skin comprising : topically applying a composi herein are also directed to a kit comprising: a daily cleansing
tion to skin , wherein the composition comprises retinalde mask ; a topical toner ; a topical skin composition compris
hyde, one or more skin conditioning agents, and optionally, ing : retinaldehyde, one or more skin conditioning agents ,
one or more additional retinoids, one or more peptides and one or more calcium containing agents , and , optionally , one
one or more calcium containing agents , wherein treating the or more additional retinoids ; and instructions for use .
skin is an improvement in a characteristic of the skin Embodiments herein are also directed to a kit comprising: a
selected from the group consisting of firmness, elasticity, daily cleansing mask ; a topical toner ; a topical skin com
fine lines and wrinkles , skin texture , dullness, dyschromia , position comprising : retinaldehyde , one or more peptides ,
skin tone , reduction or elimination of acne, and any com one or more skin conditioning agents, one or more calcium
bination thereof. Embodiments herein are also directed to a containing agents, and , optionally, one or more additional
method of treating skin comprising : (a ) exfoliating the skin ; retinoids; and instructions for use .
and (b ) topically applying a composition to skin , wherein the
composition comprises retinaldehyde , one or more skin BRIEF DESCRIPTION OF THE DRAWINGS
conditioning agents, and optionally , one or more additional [0005 ) For a better understanding of the nature and advan
retinoids, one or more peptides and one or more calcium tages of the present invention , refer to the following detailed
containing agents, wherein treating the skin is an improve description taken in connection with the accompanying
ment in a characteristic of the skin selected from the group drawings, in which :
US 2019 / 0099340 A1 Apr. 4 , 2019
[0006 ] FIG . 1 shows a view of the micro -exfoliation tool. containing retinaldehyde were much more tolerable when
[0007] FIG . 2 shows a close up of the micro -exfoliation compared with other skin compositions.
tool head , including the roller and the needles. [0025 ] It was also surprisingly found that the skin com
[ 0008 ] FIG . 3A depicts the mean change in clinical grad
ing score for fine lines (global face). FIG . 3B depicts the positions containing retinaldehyde , in place of benzoyl
mean change in clinical grading score for wrinkles (global peroxide, was tolerable and effective against mild to mod
face ). erate acne vulgaris. The skin treated with compositions
[ 0009] FIG . 4A (IRS) and FIG . 4B (adapalene) graphically described herein saw a reduction or elimination of acne .
depict tolerability results at week 2 . 10026 ] These and other embodiments will be apparent to
[ 0010 ] FIG . 5A (IRS ) and FIG . 5B (adapalene ) graphically those of skill in the art and others in view of the following
depict tolerability results at week 4 . detailed description . The present disclosure generally relates
[ 0011 ] FIG . 6A (IRS) and FIG . 6B ( adapalene) graphically to skin treatment using a retinaldehyde containing compo
depict tolerability results at week 8 .
[0012] FIG . 7A (IRS) and FIG . 7B (adapalene) graphically sition and /or a micro - exfoliation tool and / or additional
depict tolerability results at week 12 . selected skin care agents. While not wanting to be bound by
[0013 ] FIG . 8 graphically depicts the clinical grading theory , it is believed that the combination of the micro
assessment results for Intensive Renewing Serum and Ada exfoliation tool and the selected skin care agents increases
palene at week 2 . the uptake of the selected skin care agents by the epidermis
[0014 ] FIG . 9 graphically depicts the clinical grading ( outer layer of skin ) than if the skin care agent was just
assessment results for Intensive Renewing Serum and Ada placed on top of the epidermis . This is believed to be in part
palene at week 4 . because themicro -exfoliation tool increases the surface area
[0015 ] FIG . 10 graphically depicts the clinical grading of the epidermis by creating micro pores or holes in the skin ,
assessment results for Intensive Renewing Serum and Ada thereby allowing a greater number of skin cells on the
palene at week 8 . epidermis to contact and benefit from the selected skin care
[0016 ] FIG . 11 graphically depicts the clinical grading agent. One result of this is that a user can see improved
assessment results for Intensive Renewing Serum and Ada results in a shorter period of time.
palene at week 12 . 100271 Before the present compositions and methods are
[ 0017 ] FIG . 12 graphically depicts the photo comparison described , it is to be understood that this invention is not
clinical grading assessment results for Intensive Renewing limited to the particular processes , compositions, or meth
Serum and Adapalene at week 2 . odologies described , as these may vary . Moreover, the
[ 0018 ] FIG . 13 graphically depicts the photo comparison processes , compositions, and methodologies described in
clinical grading assessment results for Intensive Renewing particular embodiments are interchangeable . Therefore , for
Serum and Adapalene at week 4 . example , a composition , dosage regimens , route of admin
[ 0019 ] FIG . 14 graphically depicts the photo comparison istration , and so on described in particular embodiments
clinical grading assessment results for Intensive Renewing may be used in any of the methods described in other
Serum and Adapalene at week 8 . particular embodiments . It is also to be understood that the
[0020] FIG . 15 graphically depicts the photo comparison terminology used in the description is for the purpose of
clinical grading assessment results for Intensive Renewing describing the particular versions or embodiments only , and
Serum and Adapalene at week 12 . is not intended to limit the scope of the present invention
[0021 ] FIG . 16 graphically depicts the effect of different which will be limited only by the appended claims.
experimental conditions on IL -8 levels in tissue culture
conditioned medium , at the end of the experiment (day 14 ). 10028 ] In embodiments directed to methods which include
a series of steps, it is to be understood that the steps can
DETAILED DESCRIPTION occur in any order. Though an embodiment describes steps
(a ), (b ) and ( c ), unless specifically stated , the method can
[0022 ] Proper skin care is important for heath and cos also occur as steps (b ), ( a ), and ( c ) or ( c ), (b ) , and ( a ), or any
metic reasons . Skin is a vital organ and a breakdown in the combination of described steps. It is to be understood that
skin can adversely affect the skin 's function as a barrier and any order of steps is described and claimed herein , unless
make it susceptible to infection . A breakdown in the skin can otherwise specified .
also be very painful, such as the case of excessively dry skin .
Visual irregularities and fine lines and wrinkles in the skin [0029] Unless defined otherwise , all technical and scien
can adversely affect a person 's confidence and other peo tific terms used herein have the same meanings as com
ple' s perceptions . monly understood by one of the ordinary skill in the art .
[0023 ] There remains a need for improved methods of Although any methods similar or equivalent to those
treating skin and maintaining or improving its health and describe herein can be used in the practice or testing of
cosmetic features. It is against this background that the embodiments of the present invention , the preferred meth
present disclosure is made. ods are now described . All publications and references
[0024] Surprisingly, it has been found that using a micro mentioned herein are incorporated by reference . Nothing
exfoliation tool together with selected skin care agents herein is to be construed as an admission that the invention
results in improved skin health and appearance . It was also is not entitled to antedate such disclosure by virtue of prior
surprising that skin compositions containing retinaldehyde invention .
in place of retinol or adapalene resulted in faster and /or [0030 ] It must be noted that, as used herein , and in the
greater improvement in skin characteristics, including , firm appended claims, the singular forms “ a,” “ an ,” and “ the”
ness, elasticity , fine lines and wrinkles , skin texture , dull include plural reference unless the context clearly dictates
ness, dyschromia , and skin tone. Further, skin compositions otherwise .
US 2019 / 0099340 A1 Apr. 4 , 2019
[0031] As used herein , the term “ about” means plus or lines and wrinkles, creating a radiant complexion , shielding
minus 10 % of the numerical value of the number with which the skin again biological and environmental aggressors
it is being used . Therefore , about 50 % means in the range of associated with dry , irritated and sensitive skin , helping the
45 % -55 % . skin retain moisture and remain comfortable when chal
[0032] The term " administering " when used in conjunc lenged by climate and other environmental aggressors, rehy
tion with a therapeutic means to administer a therapeutic drating the skin , to repairing, renewing , enhancing the skin ' s
directly or indirectly into or onto a target tissue to administer natural moisture barrier, improving acne , improving mild to
a therapeutic to a patient whereby the therapeutic positively moderate acne vulgaris , reducing or eliminating the symp
impacts the tissue to which it is targeted . “ Administering " toms of acne including plugged pores, and outbreaks of
may include the act of self- administration or administration inflamed lesions or pimples .
by another person such as a health care provider . 100401 The term " inhibit," " suppress," " decrease ,” “ inter
[ 0033] As used herein , the terms " comprising ," " com fere," and /or “ reduce ” ( and like terms) generally refers to the
prise," " comprises ,” and “ comprised ” are inclusive or open act of reducing, either directly or indirectly, a function ,
ended and do not exclude additional, unrecited elements or activity, or behavior relative to the natural, expected , or
method steps. average or relative to current conditions .
[0034] As used herein , the term “ consisting essentially of” [0041] The term “ improves” is used to convey that the
or " consists essentially of” means that the composition or present invention changes either the appearance , form , char
method includes the specified components or steps and those acteristics , structure , function and /or physical attributes of
that do not materially affect the basic and novel character the skin to which it is being provided , applied or adminis
istics of the claimed invention . tered . “ Improves ” may also refer to the overall physical state
[ 0035 ] As used herein , the term “ consists of” or “ consist of an individual to whom an active agent has been admin
ing of” means that the composition or method includes only istered . For example , an individual may feel that their skin
the elements , steps, or ingredients specifically recited in the has improved ” by administration of a composition contain
particular embodiment or claim . ing an active agent.
[0036 ] Specific embodiments disclosed herein may be [0042 ] The term “ increase ," " enhance ," " stimulate ," and /
further limited in the claims using “ consisting of” or “ con or " induce” (and like terms) generally refers to the act of
sisting essentially of language , rather than “ comprising” . In improving or increasing , either directly or indirectly , the
other words, though embodiments described herein use the look and feel of the skin .
phrase " comprising” or “ comprises,” any embodiment [0043] In each of the embodiments disclosed herein , the
described herein can be replaced with “ consisting of" / compositions and methods may be utilized with or on a
" consists of” or “ consisting essentially of "/" consists essen subject in need of such treatment, which may also be
tially of.” referred to as “ in need thereof." As used herein , the phrase
[ 00371. The term “ cosmetic ” means an agent utilized , and/ " in need thereof” means that the subject has been identified
or intended to be applied to the human body for cleansing , as having a need for the particular method or treatment and
beautifying, promoting attractiveness , altering the appear that the treatment has been given to the subject for that
ance of the skin or any combination thereof. particular purpose .
[0038 ] The term “ cosmetic composition ” shall mean a [0044 ] The phrase “micro -exfoliation tool” includes the
composition including at least one active ingredient, reference to " derma roller” and “ micro -needle .”
whereby the composition is amenable to investigation for a [0045 ] " Optional” or “ optionally ” may be taken to mean
specified , efficacious outcome in a mammal ( for example , that the subsequently described component, event or cir
without limitation , a human ). Those of ordinary skill in the cumstance may or may not occur, and that the described
artwill understand and appreciate the techniques appropriate embodiments include instances where the component is
for determining whether an active ingredient has a desired included and instances where it does not.
efficacious outcome based upon the needs of the artisan . [0046 ] As used herein , the term “patient” and “ subject” are
[0039 ] The terms“ effective amount” or “ effective dose ” as interchangeable and may be taken to mean any living
used herein are interchangeable and may refer to the amount organism , which may be treated with compounds of the
of an active agent or compound or composition that has the present invention . As such , the terms" patient” and “ subject"
effect of moisturizing , cleansing, beautifying , promoting may include , but is not limited to , any non - human mammal,
attractiveness , altering the appearance of the skin , promoting primate or human . In some embodiments, the “ patient” or
the exfoliation of dry skin , promoting the digestion of " subject” is an adult , child , or infant .
desmosomes, normalizing cell maturation ,modulating kera [0047 ] The term “ retinaldehyde” is also known as retinal
tinocyte function , normalizing keratinocyte differentiation , or vitamin A aldehyde and may be used interchangeably
normalizing keratinocyte proliferation , modulating phos throughout this disclosure .
phatidylglycerol content of keratinocytes, modulating and 10048 ]. The term " skin " as used herein refers to the organ
or improving the moisture content of the skin , promoting the of the body which protects the subject from environmental
retention of long lasting hydration in the skin , increasing irritations, regulates the body 's temperature and allows for
skin moisture , improving skin water balance , increasing skin external sensations. The " skin " is separated into three layers :
hydration , decreasing transepidermal water loss, reducing the outermost layer called the epidermis which contains
evaporation of water from the skin , treating and / or prevent melanocytes ; the dermis which contains connective tissue,
ing dry and /or irritated skin , defending against, and reducing hair follicles and sweat glands; and the deepest subcutane
visible signs of aging for noticeably firmer, smoother, and ous layer called the hypodermis which is made up of fat and
flawless looking skin , erasing the appearance of premature connective tissue .
aging, including brown spots, dullness and discoloration , (0049] As used herein , the term “ topically ” and “ topical”
visibly brightening the skin , reducing the appearance of fine refers to application of the compositions of the present
US 2019 / 0099340 A1 Apr. 4 , 2019
invention to the surface of the skin and mucosal cells and anticipated that one or more members of a group may be
tissues. The skin can be anywhere or it can be specifically on included in , or deleted from , a group for reasons of conve
the face , neck , hands, or body . nience and /or patentability.
[0050] As used herein the terms “ topical formulation ” and Compositions
" topical compositions” refer to a formulation or composition
thatmay be applied to skin or a mucosa or applied trans [0057 ] Described herein are effective anti -acne composi
dermally. The skin can be anywhere or it can be specifically tions, anti-aging compositions, and skin lightening compo
on the face , neck , hands, or body. Topical formulations or sitions.
compositions may, for example , be used to confer therapeu 10058 ] Embodiments herein are directed to a skin compo
tic benefit to a patient or cosmetic benefits to a consumer. sition comprising retinaldehyde , one or more skin condi
Topical formulations or compositions are advantageous in tioning agents , and , optionally, one or more additional
that it avoids first-pass metabolism , circumvents gastroin retinoids.
testinal absorption , can allow delivery of an active ingredi [00591. Embodiments herein are directed to a skin compo
ent with a relatively short biological half- life and/or a sition comprising retinaldehyde , one or more skin condi
narrow therapeutic window , and can allow delivery of an tioning agents , one or more calcium containing agents , and ,
active ingredient to a localized spot on the skin . optionally, one or more additional retinoids.
10051] The term “ topical administration ” is used in its [0060) Embodiments herein are directed to topical skin
conventional sense to mean delivery of a substance, such as compositions comprising retinaldehyde , one or more pep
an active agent, to the skin . tides , one or more skin conditioning agents , one or more
calcium containing agents , and , optionally , one or more
[ 0052 ] The term “ transdermal administration ” is used to additional retinoids.
mean administration through the skin . Transdermal admin [0061] As described herein , skin compositions may be
istration is often applied where systemic delivery of an formulated to contain retinaldehyde in Hydroxysomes® .
active is desired , although it may also be useful for deliv Hydroxysomes are designed to dermally deliver retinalde
ering an active to tissues underlying the skin with minimal hyde with a continuous supply of calcium as nanoporous
systemic absorption . calcium phosphate particles . In some embodiments, the
[0053 ] The terms " treat,” “ treated ,” or “ treating ” as used hydroxysomes is supplied by Laboratory Skin Care , Inc.
herein refers to therapeutic treatment, cosmetic treatment [0062] The skin compositions described herein may be
and /or prophylactic or preventative measures, wherein the anhydrous , i.e . the composition does not contain water.
object is to prevent, reduce , eliminate or slow down (lessen ) [0063] As described herein , the topical skin composition
an undesired physiological condition , disorder or disease , or comprises optionally, one or more additional retinoids ,
to obtain beneficial or desired clinical results ( e.g . decrease wherein the optional one or more additional retinoids is
wrinkles, increase firmness or elasticity , improve skin tone , selected from the group consisting of retinyl palmitate ,
dullness , dyschromia, and texture, as well as a reduction or alitretinoin ( 9 - cis -retinoic acid ), tretinoin (all-trans-retinoic
elimination of acne . acid ), isotretinoin (13 - cis-retinoic acid ), etretinate, acitretin ,
adapalene , bexarotene , tazarotene, hydroxypinacolone ret
[0054 ] Unless otherwise indicated , all numbers expressing inoate (HPR ), retinoid ester, retinoate , 2 - nicotinamido )
quantities of ingredients , properties such as molecular
weight, reaction conditions , and so forth used in the speci ethyl retinoate (NEAR - 1 ) , and derivatives and combinations
fication and claims are to be understood as being modified thereof. In all forgoing embodiments , additional embodi
in all instances by the term " about." Accordingly , unless ments are described wherein the composition does not
indicated to the contrary , the numerical parameters set forth contain retinol.
in the specification and attached claims are approximations [0064] As described herein , the topical skin composition
thatmay vary depending upon the desired properties sought comprises one or more skin conditioning agents, wherein the
to be obtained by the present invention . one or more skin conditioning agents is selected from the
group consisting of cyclopentasiloxane , dimethicone, poly
[ 00551 Recitation of ranges of values herein is merely silicone - 11, ethylhexyl hydroxystearate , C12 - 15 alkyl ben
intended to serve as a shorthand method of referring indi zoate , bis - ethylhexyl hydroxydimethoxy benzylmalonate ,
vidually to each separate value falling within the range . ethoxydiglycol, hyaluronic acid , alpha hydroxyl acids, gly
Unless otherwise indicated herein , each individual value is colic acid , lactic acid , ascorbic acid , polyhydroxy acids,
incorporated into the specification as if it were individually gluconolactone , lactobionic acid , beta hydroxyl acid , peat
recited herein . All methods described herein can be per extract, glycine , cetyl alcohol, stearyl alcohol, and deriva
formed in any suitable order unless otherwise indicated tives and combinations thereof.
herein or otherwise clearly contradicted by context. The use [0065 ] As described herein , the topical skin composition
of any and all examples , or exemplary language (e. g., “ such comprises optionally one or more peptides , wherein the
as” ) provided herein is intended merely to better illuminate optional one or more peptides is selected from the group
the invention and does not pose a limitation on the scope of consisting of palmitoyl hexapeptide - 14 , oligopeptide - 10 ,
the invention otherwise claimed . No language in the speci myristoyl pentapeptide- 8 , myristoyl tetrapeptide -8 , sericin ,
fication should be construed as indicating any non - claimed silk protein , collagen , keratin , amino acids , hexapeptide - 21 ,
element essential to the practice of the invention . palmitoyl oligopeptide , palmitoyl tetrapeptide - 7 , tetrapep
[0056 ] Groupings of alternative elements or embodiments tide - 16 , polyacrylate - 13 , polyisobutene , polysorbate - 20 ,
of the invention disclosed herein are not to be construed as betaine, milk solids, rice peptides , and derivatives and
limitations . Each group member may be referred to and combinations thereof.
claimed individually or in any combination with other [0066 ] As described herein , the topical skin composition
members of the group or other elements found herein . It is comprises optionally one or more calcium containing
US 2019 / 0099340 A1 Apr. 4 , 2019
agents , wherein the optional one ormore calcium containing 1 % w /w palmitoyl hexapeptide -14 , about 0 .01 % w /w to
agents is selected from the group consisting ofhydroxyapa about 5 % w /w retinyl palmitate , about 0 .01 % w /w to about
tite , calcium lactate , calcium chloride , calcium carbonate , 5 % w / w bis - ethylhexyl hydroxydimethoxy benzylmalonate ,
calcium phosphate , calcium pyrophosphate , calcium sulfate , about 0 .001 % w / w to about 5 % w /w hydroxyapatite , and
dicalcium phosphate , dicalcium phosphate dehydrate , trical about 0 .01 % w /w to about 5 % w /w ethoxydiglycol. In
cium phosphate , calcium undecylenate, and derivatives and preferred embodiments , the topical skin composition com
combinations thereof . prises about 0 .458 % w /w retinaldehyde, about 65 . 720 % w / w
100671. In some embodiments, the topical skin composition cyclopentasiloxane, about 16 .776 % w / w dimethicone, about
further comprises niacinamide, nicotinamide, vitamin B3 , 11.842 % w /w polysilicone -11, about 2 .467 % w /w ethyl
nicotinic acid , or niacin . hexyl hydroxystearate, about 1.480 % w /w C12 -15 alkyl
[0068] As described herein , the active ingredients of the benzoate , about 0 .0009868 % w /w palmitoyl hexapeptide
skin compositions include , but are not limited to , retinalde 14 , about 0 .59 % w /w retinyl palmitate , about 0 .2 % w /w
hyde , the retinoids, the peptides , the calcium containing bis -ethylhexyl hydroxydimethoxy b enzylmalonate,
agents, and the skin conditioning agents . It is also known in 0 .0716 % w /w hydroxyapatite, and about 0 .3947 % w /w
the art that the active ingredients may be contained in such ethoxydiglycol.
compositions with cosmetically and/or pharmaceutically [0071 ] In preferred embodiments, the topical skin compo
acceptable secondary agents , such as diluents, fillers, disin sition comprises retinaldehyde, dimethicone , isododecane,
tegrants, binders , lubricants , surfactants, hydrophobic polysilicone- 11, L -ascorbic acid , dimethyl isosorbide , and
vehicles , water -soluble vehicles, emulsifiers , buffers , hvdroxypinacolone retinoate . In preferred embodiments , the
humectants , moisturizers , solubilizers , preservatives and the topical skin composition comprises about 0 . 1 % w /w to
like. The means and methods for administration are known about 1 % w /w retinaldehyde , about 50 % w /w to about 85 %
in the art and an artisan can refer to various pharmacologic w /w Gransil DMID ( combination of dimethicone , isod
references for guidance. For example , Modern Pharmaceu odecane , polysilicone - 11 ), about 5 % w /w to about 25 % w /w
tics , Banker & Rhodes, Marcel Dekker, Inc . ( 1979 ); and L -ascorbic acid , about 1 % w / w to about 10 % w / w isodode
Goodman & Gilman 's The Pharmaceutical Basis of Thera cane , about 0 . 01 % w /w to about 5 % w /w Granactive Ret
peutics, 6th Edition , MacMillan Publishing Co., New York inoid® ( combination of dimethyl isosorbide, and hvdroxypi
( 1980 ) can be consulted . nacolone retinoate).
[ 0069 ] In certain embodiments, the active ingredients [0072 ] In preferred embodiments, the topical skin compo
range from about 0 .1 % w /w to about 20 % w /w , about 1 % sition comprises retinaldehyde , water, xanthan gum , glyc
w / w to about 15 % w / w , about 2 % w / w to about 10 % w / w , erin , caprylic /Capric triglycerides , cetyl alcohol, stearyl
or about 3 % w / w to about 5 % w / w . In certain embodiments , alcohol, glyceryl stearate, PEG - 100 Stearate, dimethicone ,
the secondary ingredients range from about 0 .00001 % w / w polyacrylate - 13 , polyisobutene, polysorbate -20 , phenoxy
to about 90 % w / w , about 0 . 00001 % w / w to about 85 % w / w , ethanol, ethylhexylglycerin , and hydroxyapatite . In pre
about 0 . 00001 % w / w to about 75 % w /w , about 0 . 0001 % ferred embodiments, the topical skin composition comprises
w /w to about 70 % w / w , about 0 .001 % w / w to about 65 % about 0 . 1 % w / w to about 1 % w / w retinaldehyde, about 65 %
w / w , about 0 .01 % w / w to about 50 % w / w , about 0 . 1 % w / w w /w to about 90 % w / w water , about 0 .01 % w / w to about 1 %
to about 45 % w /w , about 1 % w / w to about 40 % w /w , about w /w xanthan gum , about 0 .01 % w / w to about 5 % w / w
5 % w / w to about 35 % w / w , about 10 % w / w to about 30 % glycerin , about 0 .01 % w / w to about 5 % w / w caprylic /Capric
w / w , or about 15 % w / w to about 25 % w /w . In preferred triglycerides, about 0 .01 % w /w to about 5 % w /w cetyl
embodiments, the topical skin composition comprises about alcohol, about 0 .01 % w /w to about 5 % w / w stearyl alcohol,
0 . 1 % w / w to about 1 % w / w retinaldehyde, about 50 % w / w about 0 .01 % w / w to about 1 % w / w Lipomulse - 165® (com
to about 75 % w /w cyclopentasiloxane, about 15 % w /w to bination of glyceryl stearate , PEG - 100 stearate ), about
about 20 % w /w dimethicone , about 10 % w / w to about 15 % 0 .01 % w / w to about 5 % w / w dimethicone , about 0 .01 % w / w
w / w polysilicone- 11, about 1 % w / w to about 5 % w /w to about 5 % w / w Sepiplus- 400® (combination of polyacry
ethylhexyl hydroxystearate , about 1 % w / w to about 5 % w /w late - 13 , polyisobutene, polysorbate - 20 ), about 0 . 01 % w /w to
C12 - 15 alkyl benzoate , about 0 .00001 % w /w to about about 5 % w /w Euxyl PE 9010® ( combination of phenoxy
0 .099 % w /w palmitoyl hexapeptide - 14 , about 0 . 1 % w /w to ethanol, ethylhexylglycerin ), and about 0 .01 % w / w to about
about 1 % w /w retinyl palmitate , about 0 . 1 % w / w to about 1 % w /w hydroxyapatite.
1 % w /w bis - ethylhexyl hydroxydimethoxy benzylmalonate , 10073 ]. The cosmetic compositions described herein may
about 0 .00001% w /w to about 0 .099 % w /w hydroxyapatite, be prepared , packaged , or sold in bulk as a single unit dose
and about 0. 1 % w /w to about 1 % w /w ethoxydiglycol. or as multiple unit doses and may be administered in the
[0070 ] In preferred embodiments, the topical skin compo conventionalmanner by any route where they are active. For
sition comprises retinaldehyde, cyclopentasiloxane, dime example, the compositions may be administered subcutane
thicone, polysilicone- 11 , ethylhexyl hydroxystearate , C12 ously , topically , and transdermally , such as in the form of
15 alkyl benzoate, palmitoyl hexapeptide -14 , retinyl patches , toners , cleanser, moisturizers, and creams. Specific
palmitate , bis - ethylhexyl hydroxydimethoxy benzylma modes of administration will depend on the indication . The
lonate , hydroxyapatite , and ethoxydiglycol. In preferred selection of the specific route of administration and the dose
embodiments , the topical skin composition comprises about regimen may be adjusted or titrated by the artisan according
0 . 1 % w / w to about 5 % w / w retinaldehyde , about 50 % w / w to known methods in order to obtain the optimal clinical
to about 90 % w /w cyclopentasiloxane, about 5 % w /w to response . All of themethods described herein may be carried
about 30 % w / w dimethicone, about 5 % w / w to about 25 % out by administering the skin compositions described herein
w /w polysilicone - 11, about 0 . 1 % w /w to about 10 % w /w by any such route for administration described herein .
ethylhexyl hydroxystearate , about 0 . 1 % w / w to about 5 % Additionally, the skin compositions disclosed herein may be
w / w C12 - 15 alkylbenzoate , about 0 . 00001 % w /w to about delivered by using any such route ofadministration for all of
US 2019 / 0099340 A1 Apr. 4 , 2019
the dosage regimens described herein . The compositions and [0080] In certain embodiments, the optional one or more
amounts of non - active ingredients in such a composition additional retinoids is selected from the group consisting of
may depend on the amount of the active ingredient. Such retinyl palmitate , alitretinoin ( 9 - cis - retinoic acid ) , tretinoin
parameters may be readily appreciated and understood by (all -trans-retinoic acid ), isotretinoin ( 13 -cis-retinoic acid ),
one of skill in the art. etretinate , acitretin , adapalene , bexarotene, tazarotene,
[0074 ] Embodiments of the invention are not limited to hydroxypinacolone retinoate (HPR ), retinoid ester, retino
any particular agent encompassed by the classes of agents ate , 2 -(nicotinamido )- ethyl retinoate (NEAR - 1 ), and deriva
described above, and any agent that falls within any of these tives and combinations thereof. In all forgoing embodi
categories may be utilized in embodiments of the invention . ments, additional embodiments are described wherein the
Non -limiting examples of such agents are provided for composition does not contain retinol . In certain embodi
clarity . Any of the secondary agents described above may be ments , the one or more skin conditioning agents is selected
useful in embodiments of the invention . from the group consisting of cyclopentasiloxane, dimethi
cone , polysilicone - 11, ethylhexyl hydroxystearate , C12 - 15
Methods of Use alkyl benzoate , bis - ethylhexyl hydroxydimethoxy benzyl
malonate , ethoxydiglycol, hyaluronic acid , alpha hydroxyl
[0075 ] Described herein are methods of treating skin acids , glycolic acid , lactic acid , ascorbic acid , polyhydroxy
wherein the skin composition is effective as an anti-acne acids , gluconolactone, lactobionic acid , beta hydroxyl acid ,
composition , an anti-aging composition , and a skin lighten peat extract, glycine, cetyl alcohol, stearyl alcohol, and
ing composition. derivatives and combinations thereof. In certain embodi
[0076 ] Embodiments herein are also directed to a method ments , the optional one ormore peptides is selected from the
of treating skin comprising: topically applying a composi group consisting of palmitoyl hexapeptide- 14 , oligopeptide
tion , as described herein , to skin , wherein treating the skin 10 , myristoyl pentapeptide - 8 , myristoyl tetrapeptide- 8 , seri
is an improvement in a characteristic of the skin selected cin , silk protein , collagen , keratin , amino acids, hexapep
from the group consisting of firmness , elasticity , fine lines tide -21, palmitoyl oligopeptide , palmitoyl tetrapeptide-7 ,
and wrinkles, skin texture, dullness, dyschromia , skin tone , tetrapeptide -16 , polyacrylate- 13 , polyisobutene, polysor
reduction or elimination of acne , and any combination bate - 20 , betaine, milk solids, rice peptides, and derivatives
thereof. and combinations thereof. In certain embodiments, the
[0077 ] In some embodiments , the method of treating skin optional one or more calcium containing agents is selected
comprises : topically applying a composition to skin , from the group consisting of hydroxyapatite , calcium lac
wherein the composition comprises retinaldehyde, one or tate , calcium chloride , calcium carbonate , calcium phos
more skin conditioning agents , and optionally , one or more phate , calcium pyrophosphate , calcium sulfate , dicalcium
additional retinoids, wherein treating the skin is an improve phosphate , dicalcium phosphate dehydrate , tricalcium phos
ment in a characteristic of the skin selected from the group phate , calcium undecylenate , and derivatives and combina
consisting of firmness , elasticity , fine lines and wrinkles, tions thereof. In some embodiments , the topical skin com
skin texture , dullness , dyschromia , skin tone, reduction or position further comprises niacinamide.
elimination of acne , and any combination thereof. In some [0081 ] In preferred embodiments , the method of treating
embodiments, the method of treating skin comprises: topi skin comprises : topically applying a composition to skin ,
cally applying a composition to skin , wherein the compo wherein the composition comprises retinaldehyde, cyclo
sition comprises retinaldehyde, one or more skin condition pentasiloxane, dimethicone , polysilicone- 11, ethylhexyl
ing agents , and one or more calcium containing agents and hydroxystearate , C12 - 15 alkylbenzoate, palmitoyl hexapep
optionally , one or more additional retinoids, wherein treating tide - 14 , retinyl palmitate , bis -ethylhexylhydroxydimethoxy
the skin is an improvement in a characteristic of the skin benzylmalonate , hydroxyapatite , and ethoxydiglycol,
selected from the group consisting of firmness, elasticity , wherein treating the skin is an improvement in a character
fine lines and wrinkles, skin texture, dullness, dyschromia , istic of the skin selected from the group consisting of
skin tone , reduction or elimination of acne, and any com firmness , elasticity , fine lines and wrinkles, skin texture ,
bination thereof. In some embodiments , the method of dullness , dyschromia , skin tone, reduction or elimination of
treating skin comprises : topically applying a composition to acne, and any combination thereof.
skin , wherein the composition comprises retinaldehyde , one [0082] In preferred embodiments, the method of treating
or more peptides, one or more skin conditioning agents , and skin comprises: topically applying a composition to skin ,
one or more calcium containing agents , and optionally , one wherein the composition comprises retinaldehyde , dimethi
or more additional retinoids, wherein treating the skin is an cone, isododecane , polysilicone- 11 , L - ascorbic acid , dim
improvement in a characteristic of the skin selected from the ethyl isosorbide , and hvdroxypinacolone retinoate, wherein
group consisting of firmness, elasticity , fine lines and treating the skin is an improvement in a characteristic of the
wrinkles , skin texture , dullness , dyschromia , skin tone , skin selected from the group consisting of firmness , elastic
reduction or elimination of acne , and any combination ity , fine lines and wrinkles, skin texture, dullness, dyschro
thereof. mia, skin tone, reduction or elimination of acne , and any
[0078 ] As described herein , skin compositions may be combination thereof
W? ..
formulated to contain retinaldehyde in Hydroxysomes® . [0083 ] In preferred embodiments, the method of treating
Hydroxysomes are designed to dermally deliver retinalde skin comprises: topically applying a composition to skin ,
hyde with a continuous supply of calcium as nanoporous wherein the composition comprises retinaldehyde , water,
calcium phosphate particles . In some embodiments, the xanthan gum , glycerin , caprylic /capric triglycerides, cetyl
hydroxysomes is supplied by Laboratory Skin Care , Inc. alcohol, stearyl alcohol, glyceryl stearate , PEG - 100 stearate ,
[0079 ] The skin compositions described herein may be dimethicone, polyacrylate - 13 , polyisobutene, polysorbate
anhydrous , i.e. the composition does not contain water. 20 , phenoxyethanol, ethylhexylglycerin , and hydroxyapa
US 2019 / 0099340 A1 Apr. 4 , 2019
tite , wherein treating the skin is an improvement in a fine lines and wrinkles, skin texture , dullness, dyschromia ,
characteristic of the skin selected from the group consisting skin tone, reduction or elimination of acne, and any com
of firmness , elasticity , fine lines and wrinkles, skin texture , bination thereof.
dullness, dyschromia , skin tone, reduction or elimination of [0088 ] In embodiments described herein , the method of
acne, and any combination thereof. treating skin comprises: (a ) rolling the skin with a micro
exfoliation tool, wherein the micro - exfoliating tool com
[ 0084 ] In some embodiments, the method of treating skin prises a handle and a head , the head comprising a roller , a
results in anti -acne , anti-aging , and skin lightening charac mechanism of mounting the roller to the handle , and one or
teristics . In some embodiments , the method of treating skin more needles fixed to the roller ; and (b ) topically applying
improves skin firmness , measured by the fullness and a composition to skin , wherein the composition comprises
plumpness of the skin . In some embodiments , the method of retinaldehyde , one or more skin conditioning agents , and
treating skin improves skin elasticity and resiliency , mea one or more calcium containing agents , and optionally , one
sured by the bounce -back of the skin . In some embodiments, or more additional retinoids , wherein treating the skin is an
the method of treating skin improves lines and wrinkles, improvement in a characteristic of the skin selected from the
measured by visible evaluation of the skin or replica analy group consisting of firmness, elasticity , fine lines and
sis . In some embodiments , the method of treating skin wrinkles , skin texture, dullness , dyschromia , skin tone ,
refines skin texture , measured by smoother, softer and more reduction or elimination of acne, and any combination
even skin . In some embodiments , the method of treating skin thereof.
improves dullness and provides a more even skin tone , [00891. The mico - exfoliation tool of the present disclosure
measured as more radiant and luminous skin . In some is designed to create micro pores , channels, or holes in the
embodiments , the method of treating skin provides in epidermis or outer layer of the skin . In some embodiments,
improvement in dyschromia ,measured as a lightening of the the micro - exfoliation tool is a roller attached to a handle or
skin . The improvement in the characteristics of the skin can wand, such as that shown in FIG . 1. FIG . 1 generally shows
be measured by ultrasound, measuring improvement in skin a micro - exfoliation tool 10 . The micro - exfoliation tool 10
density . In some embodiments, the method of treating skin includes a handle or wand 12 and a head 14 attached to the
provides an improvement in mild to moderate acne vulgaris. handle 12 . The head 14 includes a roller 16 . In some
The improvement is measured as reduction or elimination of embodiments , the head is configured as a stamp . The roller
the symptoms of acne including plugged pores, and out 16 is held in place by a mechanism ofmounting the roller to
breaks of inflamed lesions or pimples . the handle , such a mechanism is a U -shaped collar 18 that
[0085 ] Embodiments herein are also directed to a method is attached to the handle or wand 12 and engages the roller
of treating skin comprising : (a ) exfoliating the skin ; and (b ) 16 at either end in such a way that allows the roller 16 to
topically applying a composition , as described herein , to rotate . The roller 16 includes one or more needles 20 . FIG .
skin , wherein treating the skin is an improvement in a 1 shows the needles 20 in rows, but it is understood that the
characteristic of the skin selected from the group consisting needles may be arranged in a variety of configurations . The
of firmness , elasticity , fine lines and wrinkles , skin texture , micro - exfoliation tool 10 is preferably easily manufactured .
dullness, dyschromia , skin tone, reduction or elimination of In some embodiments , the handle 12 , head 14 , including the
acne , and any combination thereof . mechanism ofmounting the roller to the handle or collar 18
and the roller 16 are injection molded plastic . The needles 20
[0086 ] In embodiments described herein , the method of are preferably stainless steel, and more preferably surgical
treating skin comprises : (a ) rolling the skin with a micro grade stainless steel. In some embodiments , the one or more
exfoliation tool, wherein the micro -exfoliating tool com needles aremade of other metals , such as bronze, platinum ,
prises a handle and a head , the head comprising a roller , a gold , silver, or copper.
mechanism of mounting the roller to the handle , and one or [0090 ] FIG . 2 shows a close up of the head 14 , including
more needles fixed to the roller; and (b ) topically applying the collar 18 , roller 16 , and needles 20 . The needles 20
a composition to skin , wherein the composition comprises preferably form micro holes, pores, or channels in the
retinaldehyde , one or more peptides, one or more skin epidermis of the skin . It is understood that other structures
conditioning agents , and one or more calcium containing may be used instead of needles. When using needles, the
agents , and optionally , one or more additional retinoids, needles are preferably solid and made of stainless steel, but
wherein treating the skin is an improvement in a character can be made of other metals, such as bronze , platinum , gold ,
istic of the skin selected from the group consisting of silver , or copper. The needles are preferably from about 0 . 1
firmness , elasticity , fine lines and wrinkles , skin texture , mm to about 0 .5 mm in length so that when the micro
dullness, dyschromia , skin tone, reduction or elimination of exfoliation tool is placed on skin and rolled using moderate
acne, and any combination thereof . pressure, the needles penetrate only the epidermis , and not
[0087 ] In embodiments described herein , the method of the deeper layers of skin . In some embodiments , the needles
treating skin comprises : (a ) rolling the skin with a micro do not penetrate more than about 100 microns to 500
exfoliation tool, wherein the micro -exfoliating tool com microns into the epidermis . The needles are from about 0 . 01
prises a handle and a head , the head comprising a roller , a to about 0 . 5 mm in thickness .
mechanism of mounting the roller to the handle , and one or [0091] In some embodiments , needles 20 are configured to
more needles fixed to the roller; and (b ) topically applying transmit radio frequency (RF) or electrical stimulation
a composition to skin , wherein the composition comprises through the needles. Not wishing to be bound by theory ,
retinaldehyde , one or more skin conditioning agents , and radio frequency skin tightening is an aesthetic technique that
optionally,one or more additional retinoids, wherein treating uses RF energy to heat tissue and stimulate subdermal
the skin is an improvement in a characteristic of the skin collagen production in order to reduce the appearance of fine
selected from the group consisting of firmness, elasticity, lines and loose skin . The technique induces tissue remod
US 2019 / 0099340 A1 Apr. 4 , 2019
eling and production ofnew collagen and elastin . Low -level dullness, dyschromia , skin tone, reduction or elimination of
electrical stimulation has been shown to increase muscle acne, and any combination thereof.
mass and muscle tone , and may be useful to stimulate [0097 ] The micro -exfoliation tool, micro - dermabrasion
collagen and elastin production , and improve facial contour. paste , exfoliating scrub , or other exfoliating tool and
Additionally, electricity is used to physically enhance skin selected skin compositions can be used to treat any skin
penetration of described compositions through high voltage , surface on a human . Exemplary skin surfaces can include the
short duration pulses applied to the skin . In some embodi scalp , the face , neck , and decolletage , and the body, such as
ments , the needles 20 are configured to transmit heat. In the back , arms, legs, hands , feet, chest, stomach , and but
some embodiments , the needles 20 are configured to trans tocks . Themicro -exfoliation tool and skin care agents can be
mit ultrasound . used to treat sensitive skin such as that found on the face ,
[0092] In some embodiments, the head is configured as a neck , and decolletage as well as tough skin such as that
stamp. The stamp can be pressed against the skin using found on knees, elbows, hands, and feet. Further, the micro
moderate pressure . In some embodiments , the stamp is exfoliation tool, micro -dermabrasion paste , exfoliating
capable of vibrating. scrub , or other exfoliating tool and selected skin composi
[0093] In some embodiments , the micro -exfoliation tool tions may be used to treat a wide variety of people of all
can be scaled slightly smaller for use on the face or slightly ages, skin colors , and skin types. For example , the micro
larger for use on the body or scalp , reflecting the respective exfoliation tool, micro -dermabrasion paste , exfoliating
differences in surface area of the face versus the rest of the scrub , or other exfoliating tool and selected skin composi
tions can be used to treat people from infants , to children , to
body or scalp . During use on the face, it may be beneficial teenagers, to adults , and the elderly . The micro -exfoliation
to divide the face into sections such as the forehead , right tool, micro - dermabrasion paste, an exfoliating scrub, or
side , left side, chin , and neck . A user may then roll or press other exfoliating tool and selected skin compositions can be
the head of the micro - exfoliation tool of FIG . 1 over each used to treat a variety of skin colors including fair, olive, tan ,
section using moderate pressure . In some embodiments , it brown, and black , and all of the variations in between .
may be beneficial for the user to change the rolling direction Finally, the micro - exfoliation tool, micro - dermabrasion
with each pass . A similar method can be used when treating paste , exfoliating scrub , or other exfoliating tool and
other body parts or the scalp (i.e ., dividing into sections and selected skin compositions can be used to treat a variety of
rolling the micro - exfoliation tool over the various sections , skin types including dry , normal, oily , sensitive , and acne
changing the rolling direction from time to time). prone skin , and combinations of these .
[0094 ] In embodiments described herein , the method of [0098 ] The micro -exfoliation tool, micro - dermabrasion
treating skin comprises: (a ) exfoliating the skin using a paste , exfoliating scrub , or other exfoliating tool and
micro -dermabrasion paste , an exfoliating scrub , or other selected skin compositions can be used to treat, maintain , or
exfoliating tool; and (b ) topically applying a composition to improve a variety of skin care features or ailments such as
skin , wherein the composition comprises retinaldehyde, one skin health and integrity , skin healing, scalp irregularities or
or more peptides, one or more skin conditioning agents , and ailments , and visual or cosmetic irregularities or ailments .
one or more calcium containing agents , and optionally, one [00991. The micro - exfoliation tool, micro - dermabrasion
or more additional retinoids, wherein treating the skin is an paste , exfoliating scrub , or other exfoliating tool and
improvement in a characteristic of the skin selected from the selected skin compositions can be used to maintain skin
group consisting of firmness , elasticity , fine lines and
wrinkles, skin texture, dullness , dyschromia , skin tone , health by improving the skin integrity and water retention .
Healthy skin retains water well compared to dry skin . When
reduction or elimination of acne , and any combination the micro - exfoliation tool, micro - dermabrasion paste , exfo
thereof. liating scrub , or other exfoliating tool and selected skin
[0095 ] In embodiments described herein , the method of compositions are used as directed for a period of time, the
treating skin comprises : (a ) exfoliating the skin using a skin should have an improvement in transepidermal water
micro - dermabrasion paste , an exfoliating scrub , or other loss ( TEWL ).
exfoliating tool; and (b ) topically applying a composition to [0100] The micro -exfoliation tool, micro - dermabrasion
skin , wherein the composition comprises retinaldehyde, one paste , exfoliating scrub , or other exfoliating tool and
or more skin conditioning agents , and optionally , one or selected skin compositions can be used to maintain a healthy
more additional retinoids , wherein treating the skin is an scalp , or treat or improve scalp irregularities and ailments
improvement in a characteristic of the skin selected from the such as dandruff , dry scalp , baldness, hair thinning , and
group consisting of firmness , elasticity, fine lines and alopecia . The micro - exfoliation tool, micro -dermabrasion
wrinkles , skin texture , dullness , dyschromia , skin tone , paste , exfoliating scrub , or other exfoliating tool and
reduction or elimination of acne, and any combination selected skin compositions can also be used to improve the
thereof. health , quality, look or feel of hair by maintaining a healthy
[0096 ] In embodiments described herein , the method of scalp , or treating the scalp . For example , the micro - exfolia
treating skin comprises : (a ) exfoliating the skin using a tion tool, micro -dermabrasion paste , exfoliating scrub , or
micro -dermabrasion paste , an exfoliating scrub , or other other exfoliating tool and selected skin compositions can be
exfoliating tool; and (b ) topically applying a composition to used to improve hair texture, hair breakage ,hair volume, and
skin , wherein the composition comprises retinaldehyde, one hair shine .
ormore skin conditioning agents , and one or more calcium [0101 ] Finally, the micro - exfoliation tool, micro
containing agents, and optionally, one or more additional dermabrasion paste , exfoliating scrub , or other exfoliating
retinoids, wherein treating the skin is an improvement in a tool and selected skin compositions can be used to maintain
characteristic of the skin selected from the group consisting healthy skin , or treat or improve skin irregularities and
of firmness, elasticity, fine lines and wrinkles, skin texture, ailments such as scarring , sun damage , fine lines, deep lines
US 2019 / 0099340 A1 Apr. 4 , 2019
or wrinkles , acne, blocked pores, blackheads, dry skin , oily Hydroxysomes are designed to dermally deliver retinalde
skin , birthmarks , irregular skin tone or color, pore size , hyde with a continuous supply of calcium as nanoporous
stretch marks, uneven texture , age spots , lack of firmness or calcium phosphate particles. The skin compositions
skin tightness, cellulite , spider veins, fungus, rashes, keri described herein may be anhydrous , i. e . the composition
tosis pilaris , hair growth in the case of areas where hair does not contain water. In some embodiments, the hydroxy
growth is undesired , irritation or skin sensitivities, redness, somes is supplied by Laboratory Skin Care , Inc .
puffiness or bloating, eczema, psoriasis, and rosacea . [0105 ] As described herein , the method of treating skin
[0102] In some embodiments , the micro -exfoliation tool, comprises: topically applying a composition to skin ,
micro - dermabrasion paste , exfoliating scrub , or other exfo wherein the composition further comprises niacinamide ,
liating tool and the selected skin compositions can be used nicotinamide, vitamin B3, nicotinic acid , or niacin .
as part of a skin care regimen where particular skin com [0106 ] In preferred embodiments, the method of treating
positions, such as, moisturizers , toners , cleanser, and skin comprises: (a ) rolling the skin with a micro -exfoliation
serums, are used together with the micro - exfoliation tool. tool, wherein the micro -exfoliating tool comprises a handle
For example , when treating the scalp , it may bebeneficial to and a head , the head comprising a roller, a mechanism of
use the micro - exfoliation tool with at least one skin com mounting the roller to the handle , and one or more needles
position that is directed to maintaining, treating, or improv fixed to the roller; and (b ) topically applying a composition
ing scalp health and hair loss such as an antidandruff agent, to skin , wherein the composition comprises retinaldehyde,
a cleanser, a moisturizer , or a hair conditioner. Preferred skin cyclopentasiloxane, dimethicone, polysilicone- 11 , ethyl
care agents for the scalp include minoxidyl, coal tar, sali hexyl hydroxystearate , C12 - 15 alkyl benzoate , palmitoyl
cylic acid , selenium sulfide, sulfur, zinc pyrithione, and their hexapeptide - 14 , retinyl palmitate, bis - ethylhexyl hydroxy
derivatives and combinations . In some embodiments , itmay dimethoxybenzylmalonate, hydroxyapatite , and ethoxy
be beneficial to use the micro -exfoliation tool, micro diglycol, wherein treating the skin is an improvement in a
dermabrasion paste , exfoliating scrub , or other exfoliating characteristic of the skin selected from the group consisting
tool with an agent that is part of a shampoo, conditioner, hair of firmness , elasticity , fine lines and wrinkles , skin texture ,
mask , scalp treatment, pre -treatment, or other treatment or dullness, dyschromia, skin tone , reduction or elimination of
tonic composition . acne, and any combination thereof.
[0103 ] As described herein , the method of treating skin 0107 ] In preferred embodiments , the method of treating
comprises : topically applying a composition to skin , skin comprises : ( a ) rolling the skin with a micro - exfoliation
wherein the composition comprises optionally one or more tool, wherein the micro -exfoliating tool comprises a handle
additional retinoids, wherein the optional one or more addi and a head , the head comprising a roller, a mechanism of
tional retinoids is selected from the group consisting of mounting the roller to the handle , and one or more needles
retinyl palmitate, alitretinoin (9 -cis -retinoic acid ), tretinoin fixed to the roller ; and (b ) topically applying a composition
( all-trans -retinoic acid ), isotretinoin (13 -cis - retinoic acid ), to skin , wherein the composition comprises retinaldehyde ,
etretinate , acitretin , adapalene, bexarotene, tazarotene, dimethicone, isododecane, polysilicone - 11 , L - ascorbic acid ,
hydroxypinacolone retinoate (HPR ), retinoid ester, retino dimethyl isosorbide , and hvdroxypinacolone retinoate ,
ate, 2 -(nicotinamido) -ethyl retinoate (NEAR - 1 ), and deriva wherein treating the skin is an improvement in a character
tives and combinations thereof. In all forgoing embodi istic of the skin selected from the group consisting of
ments , additional embodiments are described wherein the firmness , elasticity, fine lines and wrinkles, skin texture ,
composition does not contain retinol. As described herein , dullness, dyschromia , skin tone, reduction or elimination of
the one or more skin conditioning agents is selected from the acne, and any combination thereof.
group consisting of cyclopentasiloxane, dimethicone , poly [0108 ] In preferred embodiments , the method of treating
silicone- 11, ethylhexyl hydroxystearate , C12- 15 alkyl ben skin comprises : ( a ) rolling the skin with a micro -exfoliation
zoate , bis -ethylhexyl hydroxydimethoxy benzylmalonate , tool, wherein the micro -exfoliating tool comprises a handle
ethoxydiglycol, hyaluronic acid , alpha hydroxyl acids , gly and a head , the head comprising a roller, a mechanism of
colic acid , lactic acid , ascorbic acid , polyhydroxy acids, mounting the roller to the handle , and one or more needles
gluconolactone, lactobionic acid , beta hydroxyl acid , peat fixed to the roller ; and (b ) topically applying a composition
extract, glycine, cetyl alcohol, stearyl alcohol, and deriva to skin , wherein the composition comprises retinaldehyde ,
tives and combinations thereof. As described herein , the water, xanthan gum , glycerin , caprylic /Capric triglycerides,
optional one or more peptides is selected from the group cetyl alcohol, stearyl alcohol, glyceryl stearate , PEG - 100
consisting of palmitoyl hexapeptide- 14 , oligopeptide - 10 , stearate , dimethicone, polyacrylate - 13 , polyisobutene, poly
myristoyl pentapeptide -8 , myristoyl tetrapeptide - 8 , sericin , sorbate - 20 , phenoxyethanol, ethylhexylglycerin , and
silk protein , collagen , keratin , amino acids , hexapeptide - 21 , hydroxyapatite , wherein treating the skin is an improvement
palmitoyl oligopeptide, palmitoyl tetrapeptide - 7 , tetrapep in a characteristic of the skin selected from the group
tide- 16 , polyacrylate -13 , polyisobutene , polysorbate - 20 , consisting of firmness, elasticity , fine lines and wrinkles,
betaine, milk solids, rice peptides, and derivatives and skin texture , dullness, dyschromia , skin tone , reduction or
combinations thereof. As described herein , the optional one elimination of acne , and any combination thereof.
or more calcium containing agents is selected from the [0109 ] In preferred embodiments, the method of treating
group consisting ofhydroxyapatite , calcium lactate , calcium skin comprises: (a ) exfoliating the skin using a micro
chloride, calcium carbonate , calcium phosphate , calcium dermabrasion paste , an exfoliating scrub , or other exfoliat
pyrophosphate, calcium sulfate, dicalcium phosphate, dical ing tool; and (b ) topically applying a composition to skin ,
cium phosphate dehydrate , tricalcium phosphate , calcium wherein the composition comprises retinaldehyde , cyclo
undecylenate , and derivatives and combinations thereof. pentasiloxane , dimethicone, polysilicone - 11, ethylhexyl
[0104 ] As described herein , skin compositions may be hydroxystearate , C12 - 15 alkyl benzoate , palmitoyl hexapep
formulated to contain retinaldehyde in Hydroxysomes® . tide - 14 , retinyl palmitate, bis -ethylhexyl hydroxydimethoxy
US 2019 / 0099340 A1 Apr. 4 , 2019
benzylmalonate , hydroxyapatite , and ethoxydiglycol, comprises retinaldehyde, one or more skin conditioning
wherein treating the skin is an improvement in a character - agents , and optionally , one or more additional retinoids ,
istic of the skin selected from the group consisting of wherein treating the skin is an improvement in a character
firmness, elasticity, fine lines and wrinkles , skin texture , istic of the skin selected from the group consisting of
dullness, dyschromia, skin tone, reduction or elimination of firmness, elasticity , fine lines and wrinkles, skin texture,
acne, and any combination thereof. dullness, dyschromia , skin tone, reduction or elimination of
[ 0110 ] In preferred embodiments , the method of treating acne , and any combination thereof. In some embodiments,
skin comprises : (a ) exfoliating the skin using a micro the method of treating skin comprises : (a ) cleansing the skin
dermabrasion paste , an exfoliating scrub , or other exfoliat with a daily cleansing mask ; (b ) topically applying a toner
ing tool; and (b ) topically applying a composition to skin , to skin ; and (c ) topically applying a composition to skin ,
wherein the composition comprises retinaldehyde , dimethi wherein the composition comprises retinaldehyde, one or
cone, isododecane , polysilicone- 11, L -ascorbic acid , dim more skin conditioning agents , and one or more calcium
ethyl isosorbide , and hvdroxypinacolone retinoate , wherein containing agents and optionally , one or more additional
treating the skin is an improvement in a characteristic of the retinoids, wherein treating the skin is an improvement in a
skin selected from the group consisting of firmness, elastic characteristic of the skin selected from the group consisting
ity , fine lines and wrinkles, skin texture , dullness , dyschro
mia, skin tone , reduction or elimination of acne, and any of firmness , elasticity , fine lines and wrinkles , skin texture ,
combination thereof . dullness , dyschromia , skin tone , reduction or elimination of
[0111 ] In preferred embodiments , the method of treating acne , and any combination thereof. In some embodiments,
skin comprises: (a ) exfoliating the skin using a micro the method of treating skin comprises : ( a ) cleansing the skin
dermabrasion paste , an exfoliating scrub , or other exfoliat with a daily cleansing mask ; (b ) topically applying a toner
ing tool; and (b ) topically applying a composition to skin , to skin ; and (c ) topically applying a composition to skin ,
wherein the composition comprises retinaldehyde , water , wherein the composition comprises retinaldehyde, one or
xanthan gum , glycerin , caprylic /Capric triglycerides , cetyl more peptides , one or more skin conditioning agents, and
alcohol, stearyl alcohol, glyceryl stearate , PEG - 100 stearate, one or more calcium containing agents , and optionally , one
dimethicone, polyacrylate- 13 , polyisobutene , polysorbate or more additional retinoids, wherein treating the skin is an
20, phenoxyethanol, ethylhexylglycerin , and hydroxyapa improvement in a characteristic of the skin selected from the
tite , wherein treating the skin is an improvement in a group consisting of firmness, elasticity , fine lines and
characteristic of the skin selected from the group consisting wrinkles, skin texture , dullness, dyschromia , skin tone,
of firmness , elasticity , fine lines and wrinkles, skin texture , reduction or elimination of acne, and any combination
dullness , dyschromia , skin tone, reduction or elimination of thereof. In certain embodiments , the optional one or more
acne , and any combination thereof . additional retinoids is selected from the group consisting of
[ 0112 ] In certain embodiments, the method further com retinyl palmitate, alitretinoin (9 -cis-retinoic acid ), tretinoin
prises a step (c ) topically applying a second agent to the skin , (all - trans -retinoic acid ), isotretinoin ( 13 -cis-retinoic acid ),
wherein the second agent is selected from the group con etretinate, acitretin , adapalene, bexarotene, tazarotene,
sisting of a cleanser , a toner, a moisturizer , a serum , and any hydroxypinacolone retinoate (HPR ), retinoid ester, retino
combination thereof. ate , 2 -(nicotinamido )- ethyl retinoate (NEAR - 1 ), and deriva
[ 0113 ] In some embodiments , the method of treating skin tives and combinations thereof. In all forgoing embodi
results in anti -acne , anti -aging , and skin lightening charac ments , additional embodiments are described wherein the
teristics . In some embodiments , the method of treating skin composition does not contain retinol. In certain embodi
improves skin firmness, measured by the fullness and ments, the one or more skin conditioning agents is selected
plumpness of the skin . In some embodiments , the method of from the group consisting of cyclopentasiloxane , dimethi
treating skin improves skin elasticity and resiliency , mea cone , polysilicone- 11 , ethylhexyl hydroxystearate , C12 - 15
sured by the bounce -back of the skin . In some embodiments , alkyl benzoate, bis -ethylhexyl hydroxydimethoxy benzyl
the method of treating skin improves lines and wrinkles , malonate , ethoxydiglycol, hyaluronic acid , alpha hydroxyl
measured by visible evaluation of the skin or by replica acids, glycolic acid , lactic acid , ascorbic acid , polyhydroxy
analysis . In some embodiments , the method of treating skin acids, gluconolactone , lactobionic acid , beta hydroxyl acid ,
refines skin texture , measured by smoother, softer and more peat extract, glycine , cetyl alcohol, stearyl alcohol, and
even skin . In some embodiments , themethod of treating skin derivatives and combinations thereof. In certain embodi
improves dullness and provides a more even skin tone , ments, the optional one or more peptides is selected from the
measured as more radiant and luminous skin . In some group consisting of palmitoyl hexapeptide - 14 , oligopeptide
embodiments, the method of treating skin provides in 10 ,myristoyl pentapeptide-8 ,myristoyl tetrapeptide - 8 , seri
improvement in dyschromia ,measured as a lightening of the cin , silk protein , collagen , keratin , amino acids, hexapep
skin . The improvement in the characteristics of the skin can tide - 21 , palmitoyl oligopeptide , palmitoyl tetrapeptide - 7 ,
be measured by ultrasound ,measuring improvement in skin tetrapeptide- 16 , polyacrylate - 13 , polyisobutene , polysor
density . In some embodiments , the method of treating skin bate - 20 , betaine, milk solids , rice peptides, and derivatives
provides an improvement in mild to moderate acne vulgaris . and combinations thereof. In certain embodiments , the
The improvement is measured as reduction or elimination of optional one or more calcium containing agents is selected
the symptoms of acne including plugged pores, and out from the group consisting of hydroxyapatite , calcium lac
breaks of inflamed lesions or pimples . tate , calcium chloride, calcium carbonate , calcium phos
[ 0114 ] In some embodiments , the method of treating skin phate , calcium pyrophosphate , calcium sulfate , dicalcium
comprises : (a ) cleansing the skin with a daily cleansing phosphate , dicalcium phosphate dehydrate , tricalcium phos
mask ; (b ) topically applying a toner to skin ; and (c ) topically phate , calcium undecylenate, and derivatives and combina
applying a composition to skin , wherein the composition tions thereof.
US 2019 / 0099340 A1 Apr. 4 , 2019
[0115 ] As described herein , the method of treating skin refines skin texture, measured by smoother, softer and more
may utilize skin compositions formulated to contain retinal even skin . In some embodiments , the method of treating skin
dehyde in Hydroxysomes® . Hydroxysomes are designed to improves dullness and provides a more even skin tone,
dermally deliver retinaldehyde with a continuous supply of measured as more radiant and luminous skin . In some
calcium as nanoporous calcium phosphate particles. In some embodiments , the method of treating skin provides in
embodiments, the hydroxysomes is supplied by Laboratory improvement in dyschromia ,measured as a lightening of the
Skin Care, Inc . skin . The improvement in the characteristics of the skin can
[ 0116 ] As described herein , the method of treating skin be measured by ultrasound, measuring improvement in skin
may utilize skin compositions described herein which are density . In some embodiments , the method of treating skin
anhydrous, i.e . the composition does not contain water. provides an improvement in mild to moderate acne vulgaris .
[0117] In some embodiments, the method of treating skin The improvement is measured as reduction or elimination of
may utilize the topical skin composition which further the symptoms of acne including plugged pores , and out
comprises niacinamide, nicotinamide , vitamin B3, nicotinic breaks of inflamed lesions or pimples.
acid , or niacin .
[0118 ] In preferred embodiments , the method of treating Kits
skin comprises: ( a ) cleansing the skin with a daily cleansing [0122] In embodiments described herein , the kit comprises
mask ; (b ) topically applying a toner to skin ; and (c ) topically a micro - exfoliation tool; a topical skin composition com
applying a composition to skin , wherein the composition prising : retinaldehyde , one or more skin conditioning agents ,
comprises retinaldehyde, cyclopentasiloxane , dimethicone , and optionally, one or more additional retinoids, and instruc
polysilicone- 11, ethylhexyl hydroxystearate , C12 - 15 alkyl tions for use . In embodiments described herein , the kit
benzoate , palmitoyl hexapeptide -14 , retinyl palmitate, bis comprises a micro -exfoliation tool; a topical skin composi
ethylhexyl hydroxydimethoxy benzylmalonate , hydroxy tion comprising: retinaldehyde, one or more skin condition
apatite , and ethoxydiglycol, wherein treating the skin is an ing agents , and one ormore calcium containing agents, and
improvement in a characteristic of the skin selected from the optionally , one ormore additional retinoids; and instructions
group consisting of firmness , elasticity, fine lines and for use . In embodiments described herein , the kit comprises
wrinkles, skin texture , dullness , dyschromia , skin tone , a micro - exfoliation tool; a topical skin composition com
reduction or elimination of acne , and any combination prising: retinaldehyde , one or more peptides, one or more
thereof. skin conditioning agents, and one ormore calcium contain
[ 0119 ] In preferred embodiments , the method of treating ing agents, and optionally, one or more additional retinoids ;
skin comprises : ( a ) cleansing the skin with a daily cleansing and instructions for use .
mask ; (b ) topically applying a toner to skin ; and (c ) topically 10123 ] In embodiments described herein , the kit comprises
applying a composition to skin , wherein the composition a micro - dermabrasion paste, an exfoliating scrub , or other
comprises retinaldehyde, dimethicone, isododecane, poly exfoliating tool; a topical skin composition comprising:
silicone- 11 , L -ascorbic acid , dimethyl isosorbide, and retinaldehyde, one or more skin conditioning agents, and
hvdroxypinacolone retinoate, wherein treating the skin is an optionally, one or more additional retinoids ; and instructions
improvement in a characteristic of the skin selected from the for use . In embodiments described herein , the kit comprises
group consisting of firmness , elasticity, fine lines and a micro - dermabrasion paste , an exfoliating scrub , or other
wrinkles , skin texture , dullness , dyschromia , skin tone , exfoliating tool; a topical skin composition comprising:
reduction or elimination of acne , and any combination retinaldehyde , one or more skin conditioning agents , and
thereof. one or more calcium containing agents , and optionally , one
[0120] In preferred embodiments , the method of treating or more additional retinoids; and instructions for use. In
skin comprises: (a ) cleansing the skin with a daily cleansing embodiments described herein , the kit comprises a micro
mask ; (b ) topically applying a toner to skin ; and (c ) topically dermabrasion paste, an exfoliating scrub , or other exfoliat
applying a composition to skin , wherein the composition ing tool; a topical skin composition comprising: retinalde
comprises retinaldehyde, water , Xanthan gum , glycerin , hyde, one or more peptides , one ormore skin conditioning
caprylic /Capric triglycerides , cetyl alcohol, stearyl alcohol, agents , and one or more calcium containing agents , and
glyceryl stearate , PEG - 100 Stearate , dimethicone, polyacry optionally, one ormore additional retinoids ; and instructions
late - 13 , polyisobutene , polysorbate -20 , phenoxyethanol, for use .
ethylhexylglycerin , and hydroxyapatite, wherein treating the [0124 ] In embodiments described herein , the kit comprises
skin is an improvement in a characteristic of the skin a daily cleansing mask ; a topical toner ; a topical skin
selected from the group consisting of firmness, elasticity , composition comprising : retinaldehyde, one or more skin
fine lines and wrinkles, skin texture , dullness, dyschromia , conditioning agents , and , optionally , one or more additional
skin tone, reduction or elimination of acne, and any com retinoids; and instructions for use . In embodiments
bination thereof. described herein , the kit comprises a daily cleansing mask ;
[ 0121] In some embodiments, the method of treating skin a topical toner; a topical skin composition comprising :
results in anti -acne, anti-aging , and skin lightening charac retinaldehyde, one or more skin conditioning agents, one or
teristics. In some embodiments , the method of treating skin more calcium containing agents, and , optionally, one or
improves skin firmness, measured by the fullness and more additional retinoids; and instructions for use . In
plumpness of the skin . In some embodiments , the method of embodiments described herein , the kit comprises a daily
treating skin improves skin elasticity and resiliency , mea cleansing mask ; a topical toner; a topical skin composition
sured by the bounce -back of the skin . In some embodiments, comprising: retinaldehyde , one or more peptides , one or
the method of treating skin improves lines and wrinkles, more skin conditioning agents , one or more calcium con
measured by visible evaluation of the skin or replica analy - taining agents , and, optionally, one or more additional
sis. In some embodiments , the method of treating skin retinoids ; and instructions for use.
US 2019 / 0099340 A1 Apr. 4 , 2019
[0125 ] The mico -exfoliation tool of the present disclosure palmitate , alitretinoin (9 -cis-retinoic acid ), tretinoin (all
is designed to create micro pores, channels, or holes in the trans-retinoic acid ), isotretinoin ( 13 -cis -retinoic acid ), etreti
epidermis or outer layer of the skin . In some embodiments , nate , acitretin , adapalene , bexarotene, tazarotene ,
the micro - exfoliation tool is a roller attached to a handle or hydroxypinacolone retinoate (HPR ), retinoid ester, retino
wand, such as that shown in FIG . 1 . FIG . 1 generally shows ate , 2 - nicotinamido ) -ethyl retinoate (NEAR - 1 ) , and deriva
a micro - exfoliation tool 10 . The micro -exfoliation tool 10 tives and combinations thereof. In all forgoing embodi
includes a handle or wand 12 and a head 14 attached to the ments, additional embodiments are described wherein the
handle 12 . The head 14 includes a roller 16 . In some composition does not contain retinol. As described herein ,
embodiments, the head is configured as a stamp. The roller the one or more skin conditioning agents is selected from the
16 is held in place by a mechanism of mounting the roller to group consisting of cyclopentasiloxane , dimethicone , poly
the handle , such as a U - shaped collar 18 that is attached to silicone - 11 , ethylhexyl hydroxystearate , C12 - 15 alkyl ben
the handle or wand 12 and engages the roller 16 at either end zoate , bis - ethylhexyl hydroxydimethoxy benzylmalonate ,
in such a way that allows the roller 16 to rotate . The roller ethoxydiglycol, hyaluronic acid , alpha hydroxyl acids, gly
16 includes one or more needles 20 . FIG . 1 shows the colic acid , lactic acid , ascorbic acid , polyhydroxy acids ,
needles 20 in rows, but it is understood that the needles may gluconolactone, lactobionic acid , beta hydroxyl acid , peat
be arranged in a variety of configurations. The micro extract, glycine , cetyl alcohol, stearyl alcohol, and deriva
exfoliation tool 10 is preferably easily manufactured . In tives and combinations thereof. As described herein , the
some embodiments, the handle 12 , head 14 , including the optional one or more peptides is selected from the group
mechanism of mounting the roller to the handle or collar 18 consisting of palmitoyl hexapeptide - 14 , oligopeptide - 10 ,
and the roller 16 are injection molded plastic . Theneedles 20 myristoyl pentapeptide - 8 , myristoyl tetrapeptide -8 , sericin ,
are preferably stainless steel, and more preferably surgical silk protein , collagen , keratin , amino acids, hexapeptide - 21 ,
grade stainless steel. In some embodiments , the one or more palmitoyl oligopeptide, palmitoyl tetrapeptide- 7, tetrapep
needles are made of other metals, such as bronze , platinum , tide - 16 , polyacrylate - 13 , polyisobutene, polysorbate - 20 ,
gold , silver, or copper . betaine , milk solids, rice peptides , and derivatives and
[0126 ] FIG . 2 shows a close up of the head 14 , including combinations thereof. As described herein , the optional one
the collar 18 , roller 16 , and needles 20 . The needles 20 or more calcium containing agents is selected from the
preferably form micro holes, pores , or channels in the group consisting of hydroxyapatite, calcium lactate, calcium
epidermis of the skin . It is understood that other structures chloride, calcium carbonate , calcium phosphate , calcium
may be used instead of needles. When using needles, the pyrophosphate, calcium sulfate , dicalcium phosphate, dical
needles are preferably solid and made of stainless steel, but cium phosphate dehydrate , tricalcium phosphate, calcium
can be made of other metals , such as bronze , platinum , gold , undecylenate , and derivatives and combinations thereof.
silver, or copper. The needles are preferably from about 0 . 1 [0130] As described herein , the topical skin composition
mm to about 0 .5 mm in length so that when the micro of the kit may utilize skin compositions formulated to
exfoliation tool is placed on skin and rolled using moderate contain retinaldehyde in Hydroxysomes® . Hydroxysomes
pressure, the needles penetrate only the epidermis, and not are designed to dermally deliver retinaldehyde with a con
the deeper layers of skin . In some embodiments, the needles tinuous supply of calcium as nanoporous calcium phosphate
do not penetrate more than about 100 microns to 500 particles . In some embodiments , the hydroxysomes is sup
microns into the epidermis. The needles are from about 0 .01 plied by Laboratory Skin Care, Inc .
to about 0 . 5 mm in thickness . [0131 ] As described herein , the topical skin composition
0127] In some embodiments , needles 20 are configured to of the kit may utilize skin compositions described herein
transmit radio frequency (RF) or electrical stimulation which are anhydrous, i.e . the composition does not contain
through the needles . Not wishing to be bound by theory , water.
radio frequency skin tightening is an aesthetic technique that [0132 ] In some embodiments , the topical skin composition
uses RF energy to heat tissue and stimulate subdermal of the kit may further comprise niacinamide , nicotinamide,
collagen production in order to reduce the appearance of fine vitamin B3, nicotinic acid , or niacin .
lines and loose skin . The technique induces tissue remod [0133] In preferred embodiments, the topical skin compo
eling and production of new collagen and elastin . Low -level sition of the kit comprises retinaldehyde, cyclopentasilox
electrical stimulation has been shown to increase muscle ane , dimethicone, polysilicone - 11 , ethylhexyl hydroxystear
mass and muscle tone, and may be useful to stimulate ate , C12 - 15 alkyl benzoate , palmitoyl hexapeptide- 14 ,
collagen and elastin production , and improve facial contour. retinyl palmitate , bis - ethylhexyl hydroxydimethoxy benzyl
Additionally, electricity is used to physically enhance skin malonate , hydroxyapatite , and ethoxydiglycol.
penetration of described compositions through high voltage , [0134] In preferred embodiments, the topical skin compo
short duration pulses applied to the skin . In some embodi sition of the kit comprises retinaldehyde, dimethicone , isod
ments, acupuncture needles 20 are configured to transmit odecane, polysilicone - 11, L -ascorbic acid , dimethyl isosor
heat. In some embodiments , acupuncture needles 20 are bide, and hvdroxypinacolone retinoate .
configured to transmit ultrasound . [0135 ] In preferred embodiments, the topical skin compo
[ 0128 ] In some embodiments, the head is configured as a sition of the kit comprises retinaldehyde, water, xanthan
stamp. The stamp can be pressed against the skin using gum , glycerin , caprylic/ Capric triglycerides, cetyl alcohol,
moderate pressure . In some embodiments , the stamp is stearyl alcohol, glyceryl stearate, PEG - 100 stearate , dime
capable of vibrating. thicone , polyacrylate - 13, polyisobutene , polysorbate - 20 ,
[0129 ] As described herein , the topical skin composition phenoxyethanol, ethylhexylglycerin , and hydroxyapatite .
of the kit comprises optionally one or more additional [0136 ] As described herein , the active ingredients of the
retinoids , wherein the optional one or more additional ret- skin compositions include, but are not limited to , retinalde
inoids is selected from the group consisting of retinyl hyde, the retinoids, the peptides, the calcium containing
US 2019 / 0099340 A1 Apr. 4 , 2019
agents , and the skin conditioning agents. It is also known in ullinumtoxin A . In some embodiments, the composition
the art that the active ingredients may be contained in such comprises pain agents such as aspirin or ibuprofen .
compositions with cosmetically and/ or pharmaceutically [0142 ] In closing, it is to be understood that the embodi
acceptable secondary agents , such as diluents, fillers , disin ments of the invention disclosed herein are illustrative of the
tegrants , binders , lubricants , surfactants , hydrophobic principles of the present invention . Other modifications that
vehicles, water -soluble vehicles, emulsifiers , buffers , may be employed are within the scope of the invention .
humectants , moisturizers , solubilizers , preservatives and the Thus , by way of example, but not of limitation , alternative
like. The means and methods for administration are known configurations of the present invention may be utilized in
in the art and an artisan can refer to various pharmacologic accordance with the teachings herein . Accordingly, the pres
references for guidance. For example , Modern Pharmaceu ent invention is not limited to that precisely as shown and
tics, Banker & Rhodes, Marcel Dekker, Inc . (1979 ); and described .
Goodman & Gilman 's The Pharmaceutical Basis of Thera
peutics, 6th Edition , MacMillan Publishing Co ., New York EXAMPLES
( 1980 ) can be consulted .
[0137] The skin compositions described herein may be Example 1: Intensive Renewing Serum Formulation
prepared , packaged , or sold in bulk as a single unit dose or [0143] The concentration of each component of an exem
as multiple unit doses and may be administered in the plary topical skin composition , referred to as Intensive
conventional manner by any route where they are active. In Renewing Serum ( IRS), can be found in Table 1 .
preferred embodiments, the topical skin composition is
provided in a capsule . Additionally, the skin compositions TABLE 1
disclosed herein may be delivered by using any such route Intensive Renewing Serum (IRS )
of administration for all of the dosage regimens described
herein . The compositions and amounts of non - active ingre Concentration
dients in such a composition may depend on the amount of INCI Range Concentration
the active ingredient. Such parameters may be readily appre
Cyclopentasiloxane 50 % -75.0 % 65.720 % w /w
ciated and understood by one of skill in the art. Dimethicone 15 % - 20. 0 % 16 .776 % w / w
[0138 ] In certain embodiments, the kit further contains Polysilicone- 11
Ethylhexyl Hydroxystearate
10 % - 15 . 0 % 11.842 % w /w
one or more skin agents , wherein the one or more skin agents 1 % - 5 .0 % 2 . 467 % w / w
are selected from the group consisting of a cleanser , a toner, C12 -15 Alkyl Benzoate 1 % -5 .0 % 1. 480 % w / w
Retinal/Retinaldehyde 0 . 1 % - 1 .0 % 0 .458 % w / w
a moisturizer and any combination thereof . Palmitoyl Hexapeptide - 14 0 .00001 % -0 .099 % 0 .0009868 % w / w
101391 In some embodiments , the instructions for use of Retinyl Palmitate 0 . 1 % - 1 .0 % 0 .59 % w /w
Bis -Ethylhexyl 0 . 1 % - 1 .0 % 0 .2 % w / w
the kit comprises language similar to the following: (a ) Roll: Hydroxydimethoxy
Divide face into sections ( forehead , right side , left side , chin Benzylmalonate
and neck ). With moderate and comfortable pressure, roll or Hydroxyapatite 0 .00001 % - 0 .099 % 0 .0716 % w / w
press the micro - exfoliating tool over each section 4 - 10 time, Ethoxydiglycol 0 . 1 % - 1. 0 % 0 . 3947 % w / w
changing directions with each pass as illustrated below . Be
sure to lift and re- apply roller when changing directions; do
not pivot when roller is in contact with skin . (b ) Apply Example 2 : Clinical Study of Efficacy and
composition : Pinch and twist off tail end of one skin Tolerance of IRS Regimen on Wrinkles and Skin
composition capsule and apply contents to face and neck Texture
area . In some embodiments, the instructions for use of the kit
further comprises ( c ) Apply an additional composition to the [0144 ] A 12 week double- blind clinical trial was per
skin of the face and neck area . formed to assess the efficacy and tolerance of Intensive
Renewing Serum ( IRS ) + REDEFINE Regimen +micro - exfo
[0140 ] In some embodiments, the instructions for use of liation tool when used by women with moderate crow 's feet
the kit comprises language similar to the following: (a ) lines and wrinkles, and moderate rough texture . The subjects
Cleanse face using daily cleansing mask . (b ) Apply topical of the study included : n = 23 females, ages 35 -65, FP I- III,
toner to skin , do not rinse off . (c ) Apply topical skin with moderate ( score of 4 -6 on modified Griffiths ' scale )
composition to skin . crow 's feet lines and wrinkles and rough texture .
[0141] In some embodiments , themethod for treating skin [0145 ] The REDEFINE Regimen includes : A ) REDE
comprises (a ) rolling the skin with a micro -exfoliation tool, FINE DAILY CLEANSING MASK (Water/Aqua/Eau ,
wherein the micro - exfoliating tool comprises a handle and a Kaolin , Butylene Glycol, Isododecane, Titanium Dioxide
head , the head comprising a roller, a mechanism of mount (CI 77891), Lauryl Methacrylate /Glycol Dimethacrylate
ing the roller to the handle , and one or more needles fixed Crosspolymer , Stearic Acid , Cetyl Alcohol, Bentonite ,
to the roller ; and (b ) topically applying a composition to Dimethicone , Glyceryl Stearate , Hydrogenated Lecithin ,
skin . In some embodiments , the composition comprises skin Magnesium Aluminum Silicate, Oleth - 10 Phosphate , PEG
lightening agents such as hydroquinone. In some embodi 100 Stearate, Sodium Lactate, Sorbitan Stearate, Tocopheryl
ments , the composition comprises anti - inflammatory com Acetate, Xanthan Gum , Fragrance /Parfum , Potassium
pounds such as corticosteroids. In some embodiments , the Hydroxide , Disodium EDTA , Hexylene Glycol, Ethylhex
composition comprises antifungals or anti-bacterial agents . ylglycerin , Caprylyl Glycol, Phenoxyethanol.) B ) REDE
In some embodiments, the composition comprises agents to FINE PORE MINIMIZING TONER (Water/Aqua/Eau ,
control rosacea such as metronidazole . In some embodi Butylene Glycol, Gluconolactone, Lactobionic Acid , Dim
ments , the composition comprises small proteins, peptides ethyl MEA , Lens Esculenta (Lentil ) Seed Extract, Sodium
and neuropeptides > 500 Daltons such as Botox or onabot Hyaluronate, Glycyrrhiza Glabra (Licorice ) Root Extract,
US 2019 / 0099340 A1 Apr. 4 , 2019
14
Panax Ginseng Root Extract, Carrageenan , PEG - 40 Hydro TABLE 3
genated Castor Oil, Polysorbate 20 , Octoxynol- 12 , Fra
grance /Parfum , Citric Acid , Ammonium Hydroxide, Capry Percentage of subjects noticing improvement.
lyl Glycol, Ethylhexylglycerin , Potassium Sorbate , Week 4 , IRS Week 8, NRS
Chlorphenesin , Phenoxyethanol.) C ) REDEFINE TRIPLE Skin Attributes treatment treatment
DEFENSE TREATMENT SPF 30 (ACTIVE INGREDI Skin radiance /luminosity / glow 96 %
ENTS : Avobenzone 3 % Homosalate 2. 5 % Octisalate 5 % 57 %
Appearance of fine lines /wrinkles 78 % 40 %
Octocrylene 2 .7 % ; INACTIVE INGREDIENTS: Water/ Skin Softness 87 % 50 %
Aqua/ Eau , Isododecane, Ethylhexyl Palmitate, Polymethyl Skin tone evenness 87 % 53 %
silsesquioxane, Glycerin , Dimethicone , Cetyl Alcohol, Skin Texture 78 % 57 %
Glyceryl Stearate, PEG - 1000 Stearate , Silica , Tetrapeptide
21, Dunaliella Salina Extract, Hydrolyzed Silk , Resveratrol,
Sodium Hyaluronate, Humic Acids, Olea Europaea (Olive) [0148 ] The clinical grading results of the clinical trial are
Fruit Extract , Camellia Oleifera Leaf Extract, Talc , Sucrose provided in Table 4 at weeks 4 and 8 after treatment with the
Stearate , Polyurethane-40 , Polysorbate 20 , Polyisobutene , REDFINE Regimen , rolling with the micro - exfoliation tool,
Polyacrylate - 13, PEG - 12 Dimethicone, Hydrogenated and treatment with IRS.
Polydecene, Fragrance/Parfum , Sorbitan Isostearate, Buty
lene Glycol, Caprylyl Glycol, Chlorphenesin , Phenoxyetha TABLE 4
nol, Methylparaben , Butylparaben , Ethylparaben , Propylpa Percentage of subjects showing improvement.
raben , Isobutylparaben , Iron Oxides.) D ) REDEFINE
OVERNIGHT RESTORATIVE CREAM (Water/Aqua/ Eau , Skin Attributes Week 4 Week 8
Isododecane , Butylene Glycol, Glycerin , Caprylic /Capric /
Myristic /Stearic Triglyceride , Niacinamide, Beeswax/ Cera Plumpness 65 % 96 %
Alba /Cire d 'abeille, Cetearyl Alcohol, Gluconolactone , Skin smoothness/roughness (tactile ) 83 % 91 %
Dimethicone, Glyceryl Stearate , PEG - 100 Stearate , Softness (tactile ) 78 % 87 %
Skin elasticity /resiliency /bounce back 78 % 83 %
Squalane , Tetrapeptide - 21 , Ascorbic Acid , Hydrolyzed Seri (' pinch recoil ')
cin , Hydrolyzed Silk , Olea Europaea (Olive ) Fruit Extract, Skin Texture (visual) 39 % 83 %
Retinyl Palmitate, Sodium Hyaluronate , Soy Isoflavones, Fine lines (crow 's feet ) 70 % 83 %
Skin radiance /luminositv /brightness 35 % 78 %
Tocopheryl Acetate, Humic Acids, Ammonium Acry Fine lines ( global face) 57 % 78 %
loyldimethyltaurate /VP Copolymer, Caprylic/ Capric Tri Firmness (tactile ) 30 % 74 %
glyceride, Cholesterol, Fragrance /Parfum , Phospholipids , Wrinkles (crow 's feet) 26 % 61 %
Polyacrylate - 13 , Polyisobutene, Polymethyl Methacrylate , Wrinkles ( global face ) 13 % 57 %
Skin tone evenness 22 % 52 %
Polysilicone - 11 , Polysorbate 20 , Sucrose Stearate, Sorbitan
Isostearate, Hexylene Glycol, Caprylyl Glycol, Potassium
Sorbate , Chlorphenesin , Phenoxyethanol, Titanium Diox [0149 ] The clinical grading results of the clinical trial
ide.) showing the comparison with the topical skin composition
[0146 ] Table 2 provides the subject rating of particular containing retinol (NRS ) and the topical skin composition of
skin attributes at weeks 4 and 8 after treatment with the the present application (IRS , containing retinaldehyde) are
REDFINE Regimen , rolling with themicro -exfoliation tool, provided in Table 5 at week 4 for the subjects treated with
and treatment with IRS . the REDFINE Regimen , rolling with the micro -exfoliation
TABLE 2
tool, and treatment with IRS versus week 8 for the subjects
treated with the REDFINE Regimen , rolling with the micro
Percentage of subjects noticing improvement. exfoliation tool, and treatment with NRS .
Skin Attributes Week 4 Week 8 TABLE 5
Skin Firmness 91 % 91 %
Appearance of fine lines/wrinkles 78 % 91% Percentage of subjects showing improvement.
Week 4 , IRS Week 8 , IRS Week 8 , NRS
Skin radiance/luminosity / glow 96 % 91 % Skin Attributes treatment treatment treatment
Skin plumpness 83 % 91 %
Skin Softness 87 % 87 % Fine lines ( global face) 57 % 78 % 37 %
Skin Texture 83 % 78 % Wrinkles (global face ) 13 % 57 % 10 %
Skin tone evenness 22 % 52 % 37 %
[ 0147 ] Surprisingly, when the topical skin composition
containing retinol (NightRenewing Serum , NRS ) was com [0150 ] The mean change in clinical grading score for fine
pared with the topical skin composition of the present lines (global face ) is provided in FIG . 3A , and wrinkles
application (IRS , containing retinaldehyde ) it was noticed ( global face ) is provided in FIG . 3B .
that subjects experienced results faster with the IRS com
position . Table 3 provides the comparision data , which [0151 ] Subjects showed a 74 % improvement in skin den
presents the results at week 4 for the subjects treated with the sity measured by ultrasound after 8 weeks of treatment with
REDFINE Regimen , rolling with the micro -exfoliation tool, the REDFINE Regimen , rolling with the micro -exfoliation
and treatment with IRS versus week 8 for the subjects tool, and treatment with IRS. Table 6 provides the mean
treated with the REDFINE Regimen , rolling with the micro ultrasound measurement and change from baseline at weeks
exfoliation tool, and treatment with NRS. 4 and 8 .
US 2019 / 0099340 A1 Apr. 4 , 2019
15
TABLE 6 mula: Isododecane , Cyclopentasiloxane , Cyclohexasilox

ane, Dimethicone /Bis- Isobutyl PPG - 20 Crosspolymer,
Mean Ultrasound Measurement and Change From Baseline. Ethoxydiglycol, Ascorbic Acid , Caprylic /Capric Triglycer
Baseline : Week 4 Week 8 ide, Kojic Acid , Ethylhexyl Hydroxystearate, Polysilicone
29 .31 32. 40 33. 84
11, Syringa Vulgaris (Lilac ) Leaf Cell Culture Extract,
Change from BL Increase 11 % Increase 16 % Maltodextrin . Retinol Formula : Water/Aqua/ Eau , Caprylic /
Capric Triglyceride, Butyrospermum Parkii (Shea ) Butter,
Glycerin , Glyceryl Stearate , Ethoxydiglycol, Butylene Gly
[0152] Table 7 provides the objective ( clinical) assessment col , Carthamus Tinctorius (Safflower ) Seed Oil , Stearic
of tolerability, all results at weeks 1 , 4 , and 8 fall into the Acid , Polysorbate 60, Stearyl Alcohol, Cyclopentasiloxane,
very mild or mild category and is considered tolerable . Cyclohexasiloxane , Retinol, Dipotassium Glycyrrhizate ,
Glycyrrhiza Glabra (Licorice ) Root Extract, Sodium
TABLE 7 Hyaluronate , Sorbitol, Tocopheryl Acetate, Fragrance/Par
Percentage of Subjects with Skin Ailment Compared to Baseline . fum , Polysorbate 20 , Carbomer, Triethanolamine, Glyceryl
Acrylate /Acrylic Acid Copolymer, Caprylyl Glycol, Hex
Skin Ailment Week 1 Week 4 Week
Wee. 8 ylene Glycol, Ethylhexylglycerin , BHT, Citric Acid , Diso
dium EDTA , Phenoxyethanol, Methylparaben , Propylpara
Erythema 4% 13 % 4%
ben , Citral , Hydroxyisohexyl 3 - Cyclohexene
Burning 0% 0% 0%
Edema 0% 0% 0% Carboxaldehyde, Limonene, Linalool, Yellow 5.)
Stinging 4% 0% 0% [0155 ] Table 8 provides the subject rating of particular
Dryness 9% 0% 4%
Tightness 4% 0% 4 skin attributes at weeks 4 and 8 after treatment with the
Itching 0% 0% 0% REVERSE Regimen , rolling with themicro - exfoliation tool ,
and treatment with IRS .
Example 3: Clinical Study of Efficacy and TABLE 8

Tolerance of IRS Regimen on Dyschromia , Percentage of subjects noticing improvement.
Dullness and Wrinkles
Skin Attributes Week 4 Week 8
[0153] A 12 week double -blind clinical trial was per
formed to assess the efficacy and tolerance of Intensive Appearance of fine lines/wrinkles 90 % 95 %
Renewing Serum (IRS) + REVERSE Regimen + micro -exfo Skin radiance / luminosity/ glow 84 % 84 %
liation tool when used by women with moderate dyschromia Skin tone evenness 84 % 84 %
Skin Softness 84 % 84 %
on the face, mild to moderate dullness and global face lines Skin plumpness 79 % 84 %
and wrinkles . The subjects included : n = 19 females , ages Skin Firmness 79 % 79 %
35 -65 , FP I- IV (at least 60 % FP I- III ), with moderate ( score Skin Texture 84 % 79 %
of 4 -6 on modified Griffiths' scale ) dyschromia , 40 -60 %
with moderate discrete HP ( age spots ), 10 - 20 % with
melisma ( as confirmed by Woods lamp ), and with mild to [0156 ] The clinical grading results of the clinical trial are
moderate ( 3 - 6 on modified Griffiths' scale ) dullness and provided in Table 9 at weeks 4 and 8 after treatment with the
global face lines /wrinkles. REVERSE Regimen , rolling with the micro - exfoliation tool,
10154 ] The REVERSE Regimen includes: A ) REVERSE and treatment with IRS .
DEEP EXFOLIATING WASH (Water/Aqua / Eau , C12 - 15
Alkyl Benzoate , Diethylhexyl Sebacate , Polylactic Acid , TABLE 9
Cetearyl Alcohol, Jojoba Esters, PEG - 40 Stearate , Glyceryl Percentage of subjects showing improvement.
Stearate , Ammonium Laureth Sulfate, Magnesium Alumi
num Silicate , Pentylene Glycol, Potassium Cetyl Phosphate , Skin Attributes Week 4 Week 8
Ceteareth - 20 , Hydroxyacetophenone, Lactic Acid , Mentha Skin elasticity/resiliency/bounce back 95 % 95 %
Piperita (Peppermint) Oil, Fragrance/Parfum , Xanthan (' pinch recoil')
Gum , Glycolic Acid , Sodium Magnesium Silicate, Propyl Fine lines (crow 's feet ) 84 % 95 %
ene Glycol, Citric Acid , Phenoxyethanol, Potassium Sor Skin smoothness/roughness (tactile )
Fine lines ( global face)
90 %
53 %
90 %
bate , Hydroxyisohexyl 3 -Cyclohexene Carboxaldehyde , 79 %
84 %
84 %
Softness (tactile )
Limonene , Linalool, Yellow 5 ( CI 19140 ), Yellow 6 .) B ) Firmness (tactile ) 26 % 79 %
REVERSE INTENSIVE BRIGHTENING TONER (Water / Plumpness 63 % 79 %
Aqua /Eau , Hamamelis Virginiana (Witch Hazel) Water , Skin Texture (visual)
Skin radiance/luminosity /brightness
53 %
53 %
74 %
68 %
Butylene Glycol, Polysorbate 20 , Ethoxydiglycol, Alcohol, Wrinkles (crow 's feet) 37 % 63 %
Kojic Acid , Dipotassium Glycyrrhizate , Glycyrrhiza Glabra Skin tone evenness 26 % 58 %
(Licorice ) Root Extract, Salicylic Acid , Phenylethyl Resor Wrinkles (global face ) 5% 26 %
cinol, Tocopherol, Alanine, Glycine , Isoleucine , Leucine ,
Fragrance / Parfum , Sodium Sulfite , PEG - 12 Dimethicone ,
Sodium Metabisulfite , Sodium Hydroxide , Citric Acid , [0157] Subjects showed a 78 % improvement in skin firm
Disodium EDTA , Caprylyl Glycol, Chlorphenesin , Phe ness measured by Ro (extensibility ) after 8 weeks of treat
noxyethanol, Citral, Hydroxyisohexyl 3 -Cyclohexene Car ment with the REVERSE Regimen , rolling with the micro
boxaldehyde, Limonene , Linalool.) C ) REVERSE DUAL exfoliation tool, and treatment with IRS. A decrease in Ro
ACTIVE BRIGHTENING COMPLEX (Vitamin C For ( extensibility ) correlates to improvement in skin firmness.
US 2019 / 0099340 A1 Apr. 4 , 2019
16
Table 10 provides the percentage of subjects showing Dimethicone, Fragrance /Parfum , Retinol, Ascorbyl Palmi
improvement in R , and change from baseline atweeks 4 and tate , Magnesium Ascorbyl Phosphate , Lactic Acid , Arcto
staphylos Uva Ursi Leaf Extract, Sodium C14 - 16 Olefin
Sulfonate, Sodium Metabisulfite , Laureth -7 , Glyceryl Stear
TABLE 10 ate, PEG -100 Stearate , Tocopheryl Acetate , Citric Acid ,
Glycine Soja (Soybean ) Oil , Propylene Glycol, Disodium
Percent Improvement in Ro and Change From Baseline. EDTA , BHT,Methylparaben , Propylparaben , Benzoic Acid ,
Week 4 Week 8 Sorbic Acid , Chlorphenesin , Imidazolidinyl Urea , Phenoxy
ethanol, Hydroxyisohexyl 3 -Cyclohexene Carboxaldehyde ,
37 % 78 % Limonene , Linalool, Yellow 5 , Yellow 6 .)
Change from BL Increase 7 % Decrease 21 %
[0161 ] Table 12 provides the subject rating of particular
[0158 ] Table 11 provides the objective (clinical) assess skin attributes at weeks 4 and 8 after treatment with the HQ
ment of tolerability , all results at weeks 1 , 4 , and 8 fall into Regimen and treatment with IRS .
the very mild or mild category and is considered tolerable . TABLE 12
TABLE 11 Percentage of subjects noticing improvement.
Percentage of Subjects with Skin Ailment Compared to Baseline. Skin Attributes Week 4 Week 8
Skin Ailment Week 1 Week 4 Week 8 Skin radiance / luminosity/ glow 75 % 95 %
Dryness 11 % 16 % 5% Skin Firmness 75 % 90 %
Erythema
Burning
5% 11 % 0% Skin Texture 75 % 90 %
0% 11 % 5% Skin plumpness 75 % 90 %
Tightness 0% 11 % 5% Skin Softness 80 % 85 %
Stinging 0% 5% 5% Appearance of fine lines/wrinkles 60 % 80 %
Itching 0% 5% 0%
Edema 0% 0% 0%
[0162] The clinical grading results of the clinical trial are
provided in Table 13 at weeks 4 and 8 after treatment with
Example 4 : Clinical Study of Efficacy and the HQ Regimen and treatment with IRS.
Tolerance of IRS Regimen on Dyschromia ,
Dullness and Wrinkles TABLE 13
[0159 ] A 12 week double -blind clinical trial was per Percentage of subjects showing improvement.
formed to assess the efficacy and tolerance of Intensive Skin Attributes Week 4 Week 8
Renewing Serum (IRS) + REVERSE Lightening (HQ ) Regi
men when used by women with moderate dyschromia on the Skin smoothness / roughness (tactile ) 95 % 95 %
face, mild to moderate dullness and global face lines and Softness ( tactile ) 85 % 95 %
wrinkles . The subjects included : n = 20 females , ages 35 -65, Fine lines ( global face) 65 % 95 %
Fine lines ( crow 's feet) 65 % 90 %
FP I- IV (at least 60 % FP I- III ), with moderate ( score of 4 - 6 Skin elasticity/resiliency/bounce back 70 % 85 %
on modified Griffiths' scale ) dyschromia , 40 -60 % with mod ('pinch recoil ')
erate discrete HP (age spots ), 10 - 20 % with melisma (as Plumpness 60 % 85 %
confirmed by Woods lamp ), and with mild to moderate (3 - 6 Skin Texture (visual) 40 % 85 %
on modified Griffiths' scale ) dullness and global face lines/ Skin radiance /luminosity /brightness 40 % 75 %
Firmness (tactile ) 35 % 70 %
wrinkles. Skin tone evenness 25 % 70 %
[0160 ] The REVERSE Lightening (HQ) Regimen Wrinkles (global face )
Wrinkles (crow 's feet )
30 %
15 %
50 %
35 %
includes: A ) REVERSE SKIN LIGHTENING TONER
(ACTIVE INGREDIENT: Hydroquinone 2 % ; INACTIVE
INGREDIENTS : Water/ Aqua /Eau , Ethoxydiglycol, Hama [0163] Subjects showed a 74 % improvement in skin firm
melis Virginiana (Witch Hazel) Water, Methylpropanediol,
Alcohol, Polysorbate 20, Kojic Acid , Salicylic Acid , Mag ness measured by R . (extensibility ) after 8 weeks of treat
nesium Ascorbyl Phosphate , Arctostaphylos Uva Ursi Leaf ment with the HQ Regimen and treatment with IRS. A
Extract, Arnica Montana Flower Extract, Citrus Limon decrease in R , (extensibility ) correlates to improvement in
skin firmness. Table 14 provides the percentage of subjects
(Lemon ) Peel Extract, Foeniculum Vulgare (Fennel) Fruit showing improvement in R , and change from baseline at
Extract, Sodium Sulfite , Fragrance /Parfum , PEG - 12 Dime
thicone , Zinc Phenolsulfonate , Citric Acid , Sodium Meta weeks 4 and 8 .
bisulfite , Sodium Hydroxide , Propylene Glycol, Phenoxy
ethanol, Chlorphenesin , DMDM Hydantoin , Benzoic Acid , TABLE 14
Sorbic Acid , Hydroxyisohexyl 3 -Cyclohexene Carboxalde Percent Improvement in Ro and Change From Baseline .
hyde, Limonene , Linalool, Yellow 5 , Yellow 6 .) B )
REVERSE SKIN LIGHTENING TREATMENT (ACTIVE Week 4 Week 8
INGREDIENT: Hydroquinone 2 % ; INACTIVE INGREDI 30 % 74 %
ENTS : Water /Aqua /Eau , Ethoxydiglycol, Cetearyl Alcohol, Change from BL Increase 17 % Decrease 14 %
PPG - 12/SMDI Copolymer, Diethylhexyl Sebacate, Poly
acrylamide, Ceteareth -20 , Glycerin , C13 - 14 Isoparaffin ,
US 2019 / 0099340 A1 Apr. 4 , 2019
17
[0164 ] Table 15 provides the objective (clinical) assess ethanol, Potassium Sorbate , Sodium Benzoate, Citronellol,
ment of tolerability, all results at weeks 1 , 4 , and 8 fall into Geraniol, Linalool, Mica , Titanium Dioxide.) C ) SOOTHE
the very mild or mild category and is considered tolerable . MOISTURE REPLENISHING CREAM (Water /Aqua /Eau ,
Dimethicone, Glycerin , Pentylene Glycol, Ammonium
TABLE 15 Acryloyldimethyltaurate /VP Copolymer , Echium Plan
Percentage of Subjects with Skin Ailment Compared to Baseline . tagineum Seed Oil, Chamomilla Recutita (Matricaria )
Flower Extract, Olea Europaea (Olive ) Fruit Oil, Vitis
Skin Ailment Week 1 Week 4 Week 8 Vinifera (Grape ) Seed Oil , Pichia Anomala Extract, Ascor
Erythema 5% 25 % 10 % byl Palmitate , Tocopherol, Triacetin , Hydrogenated Leci
Dryness 20 % 20 % 10 % thin , Carnitine , Canola Oil/Huile de colza , Urea , Lecithin ,
Burning
Tightness
5%
15 %
10 %
10 %
5%
5%
Carbomer, Dimethicone /Vinyl Dimethicone Crosspolymer,
Stinging 0% 5% 5% Glyceryl Oleate , Glyceryl Stearate , Polysilicone- 1 , Sodium
Itching 5% 5% 0% Hydroxide, Xanthan Gum , Citric Acid , BHT, Ethylhexyl
Edema 5% 0% 0% glycerin , Potassium Sorbate, Sodium Benzoate, Benzyl
Alcohol, Phenoxyethanol.)
Example 5 : Clinical Study of Efficacy and [0167] Table 16 provides the subject rating of particular
Tolerance of IRS Regimen on Wrinkles skin attributes at weeks 6 and 10 after treatment with the
SOOTHE Regimen and treatment with IRS .
[0165 ] A 14 week double -blind clinical trial was per
formed to assess the efficacy and tolerance of Intensive TABLE 16
Renewing Serum (IRS) + SOOTHE Regimen when used by
women with moderate lines and wrinkles at crow ' s feet and Percentage of subjects noticing improvement from week 2.
under eye areas, some having mild to moderate redness and Skin Attributes Week 6 Week 10
some having self -perceived reactive and sensitive skin . The
subjects included : n = 24 females, ages 35 -65, FP I- IV , with Appearance of fine lines /wrinkles 67 % 88 %
mild to moderate (score of 3 -6 on modified Griffiths ' scale ) Skin plumpness 63 % 88 %
lines and wrinkles in the crow 's feet area and under eye area , Skin Firmness 71 % 75 %
approximately 60 % with mild to moderate ( score of 3 - 6 on Skin tone evenness 67 % 75 %
modified Griffiths' scale ) redness on the global face , Skin Softness 63 % 75 %
approximately . 40 % with reactive and sensitive skin as Skin radiance/luminosity/ glow 67 % 71 %
Skin Texture 63 % 63 %
determined by 4 Cosmetic Intolerance Screener questions .
Subjects used the SOOTHE Regimen only for weeks 1 and
2 , starting in week 3 the subjects also treated skin with IRS.
[0166 ] The SOOTHE Regimen includes: A ) SOOTHE [0168 ] The clinical grading results of the clinical trial are
GENTLE CREAM WASH (Water/Aqua /Eau , Caprylic /Ca provided in Table 17 at weeks 6 and 10 after treatment with
pric Triglyceride , Glycerin , Cyclopentasiloxane , Propane the SOOTHE Regimen and treatment with IRS.
diol, Isostearyl Alcohol, Aloe Barbadensis Leaf Juice, Cer
amide NP, Ceramide EOP, Ceramide AP, Caffeine , TABLE 17
Tocopheryl Acetate , Bisabolol, Butylene Glycol Cocoate , Percentage of subjects showing improvement.
Acrylates/C10 - 30 Alkyl Acrylate Crosspolymer, Xanthan
Gum , Ethylcellulose , Aminomethyl Propanol, Sodium Lau Skin Attributes Week 6 Week 10
royl Lactylate, Tropolone, Phytosphingosine, Cholesterol, Fine lines (under eye) 79 % 100 %
Carbomer, 1, 2 -Hexanediol, Caprylyl Glycol, Potassium Sor Softness ( tactile ) 83 % 100 %
bate, Sodium Benzoate, Ethylhexylglycerin , Phenoxyetha Skin elasticity /resiliency/bounce back 92 % 92 %
nol.) B ) SOOTHE SENSITIVE SKIN TREATMENT (AC ('pinch recoil ')
TIVE INGREDIENTS: Allantoin 0 . 5 % , Dimethicone 2 .9 % ; Fine lines ( global face ) 67 % 92 %
INACTIVE INGREDIENTS: Water/Aqua /Eau , Glycerin , Wrinkles (crow 's feet) 42 % 92 %
Fine lines (crow 's feet) 63 % 92 %
Isododecane, Sodium Acrylates Copolymer , Oryza Sativa Skin smoothness/roughness (tactile ) 83 % 92 %
(Rice) Bran Extract, Chamomilla Recutita (Matricaria ) Plumpness 63 % 92 %
Flower Extract, Pelargonium Graveolens Flower Oil , Skin radiance /luminosity /brightness 75 % 88 %
Lavandula Angustifolia (Lavender ) Oil, Boswellia Serrata Evenness of skin tone (redness ) 58 % 83 %
Skin Texture ( visual) 50 % 75 %
Extract, Oligopeptide - 10 , Tetrapeptide - 16 , Tocopherol, Wrinkles (under eye ) 42 % 71 %
Tropolone , Tranexamic Acid , Honey Extract, Glycine Soja Firmness (tactile ) 46 % 67 %
(Soybean ) Germ Extract, Perilla Ocymoides Seed Oil , Wrinkles ( global face ) 21 % 67%
Helianthus Annuus (Sunflower ) Seed Oil, Bisabolol,
Angelica Polymorpha Sinensis Root Extract, Linoleic Acid ,
Linolenic Acid , Butylene Glycol, Coco - Caprylate/ Caprate , [0169 ] Subjects showed a 73 % improvement in skin firm
Decyl Glucoside , Dimethylacrylamide/Acrylic Acid /Poly ness measured by R . ( extensibility ) after 10 weeks of
styrene EthylMethacrylate Copolymer, Hydrogenated Poly treatment with the SOOTHE Regimen and treatment with
isobutene, Lysolecithin , PEG -40 Stearate , Phospholipids, IRS . A decrease in Ro (extensibility ) correlates to improve
Polyglyceryl-10 Stearate , Polysilicone - 11, Xanthan Gum , ment in skin firmness. Table 18 provides the percentage of
Hexylene Glycol, Tin Oxide , 1,2 -Hexanediol, CaprylylGly subjects showing improvement in Ro and change from
col, Chlorhexidine Digluconate, Chlorphenesin , Phenoxy baseline at weeks 6 and 10 .
US 2019 /0099340 A1 Apr. 4 , 2019
TABLE 18 tate , Atelocollagen , Zinc Phenosulfonate , Lecithin , PEG - 12

Dimethicone, Benzophenone - 9 , Xanthan Gum , Sodium
Percent Improvement in R , and Change From Baseline. Chondrotin Sulfate , Fragrance /Parfum , Butylene Glycol,
Week 6 Week 10 Propylene Glycol, Disodium EDTA , DMDM Hydantoin ,
Chlorphenesin , Phenoxyethanol, Citronellol, Geraniol,
Change from BL
46 %
Decrease 1 %
73 %
Decrease 30 %
Limonene, Linalool, Blue 1, Red 33.) C ) UNBLEMISH
DUAL INTENSIVE ACNE TREATMENT (ACTIVE
INGREDIENT: Benzoyl Peroxide 5 % ; INACTIVE INGRE
[0170 ] Table 19 provides the objective (clinical) assess DIENTS : Lotion : Water/Aqua /Eau , Glycerin , Polyacrylam
ment of tolerability , nearly all results at weeks 2, 4 , and 6 fall ide, Benzyl Alcohol, C13 - 14 Isoparaffin , Allantoin , Niaci
into the very mild or mild category and is considered namide , Panthenol, Ceramide AP, Ceramide NP, Ceramide
tolerable , the only exception was for erythema at week 6 EOP, Aloe Barbadensis Leaf Juice, Chamomilla Recutita
which falls into the moderate category but is still considered (Matricaria ) Flower Extract, Punica Granatum Extract,
tolerable. No irritation was observed at week 10 . Yucca Glauca Root Extract, Biosaccharide Gum - 1 , Phy
tosphingosine, Cholesterol, Xanthan Gum , Carbomer, Diso
TABLE 19 dium Oleamido MEA - Sulfosuccinate , Laureth - 7 , Sodium
Lauroyl Lactylate , Sodium Sulfite , Disodium EDTA , Pro
Percentage of Subjects with Skin Ailment Compared to Baseline. pylene Glycol, Phenoxyethanol. Enhancement Gel: Water /
Skin Ailment Week 2 Week 4 Week 6 Aqua /Eau , Ethoxydiglycol , Corn Starch Modified , PEG -7
Glyceryl Cocoate , Phenoxyethanol, Carbomer, Trietha
Scaling/peeling 4% 8% 8% nolamine, Fragrance /Parfum , BHT, Disodium EDTA , Eth
Erythema 0% 0% 4% ylhexylglycerin , Citronellol,Geraniol, Limonene, Linalool.)
Irritant folliculitis 0% 0% 0%
Burning 0% 0% 0% D ) UNBLEMISH OIL CONTROL LOTION SPF 20 (AC
Edema 0% 0% 5% TIVE INGREDIENTS ; Zinc Oxide 4 .75 % , Titanium Diox
Stinging 0% 0% 0% ide 0 . 7 % ; INACTIVE INGREDIENTS : Water /Aqua /Eau ,
Itching 0% 0% 0% Cyclopentasiloxane , Isododecane , Pentylene Glycol, Cet
earyl Alcohol, Polysilicone - 11, Butylene Glycol, PEG - 10
Dimethicone, Dimethicone , Azelaic Acid , Tetrahexyldecyl
Example 6 : Clinical Study of Efficacy and Ascorbate , Tocopherol, Boerhavia Diffusa Root Extract,
Tolerance of IRS Regimen on Acne Vulgaris Atelocollagen , Nordihydroguaiaretic Acid , Oleanolic Acid ,
[ 0171] A 12 week double -blind clinical trial was per Lecithin , Tropolone, PEG -60 Almond Glycerides ,Glycerin ,
Cholesterol, Squalane , Glyceryl Stearate , PEG - 100 Stearate ,
formed to assess the efficacy and tolerance of Intensive Stearic Acid, Xanthan Gum , Polysorbate 60 , Dimethiconol,
Renewing Serum (IRS ) + UNBLEMISH Regimen when used Ceteth - 10 Phosphate, Dicetyl Phosphate, Hexyl Laurate ,
by women with mild to moderate acne vulgaris . The subjects Polyglyceryl- 4 Isostearate , Sorbitan Isostearate , Alumina ,
included : n = 23 females , ages 22 - 45 , FP I - VI, with mild to Hydroxyethyl.)
moderate ( score of 2 - 3 on IGA scale ) acne vulgaris , having
a minimum of 5 inflammatory lesions on the face , having [0173 ] Table 20 provides the subject rating of particular
skin attributes at weeks 4 and 8 after treatment with the
mild to moderate (score of 1 -6 on 0 - 9) crow ' s feet wrinkles UNBLEMISH Regimen and treatment with IRS .
(a minimum 50 % of panel (approx . 15 subjects ) had a
crow 's feet wrinkle score of 2 -6 (on a 0 - 9 ) and underwent TABLE 20
skin replicas and ultrasound ), having mild to moderate
( score of 3 - 6 on 0 - 9 ) skin clarity . Percentage of subjects noticing improvement.
[0172 ] The UNBLEMISH Regimen includes the follow
ing : A ) UNBLEMISH ACNE TREATMENT SULFUR Skin Attributes Week 4 Week 8
WASH (ACTIVE INGREDIENT: Sulfur 3 % ; INACTIVE Skin smoothness 74 % 87 %
INGREDIENTS : Water/Aqua /Eau , Sodium Laureth Sulfate , Skin Softness 65 % 83 %
Propylene Glycol, Distearyl Phthalic Acid Amide , Lauryl Evenness of skin texture
Skin Firmness
74 %
57 %
78 %
78 %
Glucoside, Aloe Barbadensis Leaf Juice, Diisodecyl Adi Evenness of skin tone 52 % 78 %
pate, Glycerin , Hydrogenated Polyisobutene, Polyacrylam Skin fullness/ plumpness 52 % 74 %
ide , Cetearyl Alcohol, Titanium Dioxide (CI 77891 ), Arnica Skin radiance 48 % 70 %
Montana Flower Extract, Camellia Sinensis Leaf Extract, Lines/wrinkles 43 % 70 %
Cetyl Alcohol, Magnesium Aluminum Silicate , Ceteareth
20 , Laureth -7 , PEG - 100 Stearate, C13 - 14 Isoparaffin , Bis [0174 ] The clinical grading results of the clinical trial are
abolol, Glyceryl Stearate , Xanthan Gum , Fragrance/ Parfum , provided in Table 21 at weeks 4 and 8 after treatment with
Methylparaben , Glutaral, Chlorphenesin , Diazolidinyl Urea , the UNBLEMISH Regimen and treatment with IRS .
Phenoxyethanol, Propylparaben , Citronellol, Geraniol,
Limonene , Linalool, Violet 2 , Red 33 .) B ) UNBLEMISH TABLE 21
CLARIFYING TONER (Water/ Aqua / Eau , Hamamelis Vir
giniana (Witch Hazel) Water, Ethoxydiglycol, Aloe Bar Percentage of subjects showing improvement.
badensis Leaf Juice , Glycolic Acid , Polysorbate 20 , Alcohol,
Sodium Hydroxide , Panthenol, Camellia Sinensis Leaf Skin Attributes Week 4 Week 8
Extract, Rosmarinus Officinalis (Rosemary ) Leaf Extract, Skin smoothness/roughness (tactile ) 100 % 100 %
Sodium Hyaluronate , Leuconostoc/Radish Root Ferment Skin Texture (visual) 100 % 100 %
Filtrate, Arginine, Niacinamide, Azelaic Acid , Menthyl Lac
US 2019 / 0099340 A1 Apr. 4 , 2019
TABLE 21 -continued Example 7 : Silicone Gel with Retinal Formulation

Percentage of subjects showing improvement. [0179 ] The concentration of each component of an exem
plary topical skin composition , referred to as silicone gel
Skin Attributes Week 4 Week 8 with retinal, can be found in Table 25 .
Skin radiance /luminosity /brightness 65 % 91 %
Skin tone evenness 57 % 70 % TABLE 25
Plumpness 35 % 70 %
Fine lines (crow 's feet) 30 % 35 % Silicone Gel with Retinal
Wrinkles (global face ) 22 % 30 %
Fine lines (global face) 17 % 26 % INCI Concentration
Wrinkles (crow 's feet ) 22 % 22 %
Firmness (tactile ) 9% 22 % Retinal/Retinaldehyde 0 . 125 %
Skin elasticity/resiliency /bounce back 13 % 13 % Dimethicone , Isododecane , Polysilicone - 11 79 .000 %
(' pinch recoil ) L -ascorbic acid 15 .000 %
Isododecane 4 .875 %
Dimethyl Isosorbide and Hydroxypinacolone Retinoate 1. 00 %
[0175 ] Subjects showed a mean reduction in crow 's feet
when measured by replica analysis .
[0176 ] Table 22 provides the results of a global acne Example 8: Emulsion with Retinal Formulation
assessment and lesion count at weeks 4 and 8 after treatment
with the UNBLEMISH Regimen and treatment with IRS. [0180 ] The concentration of each component of an exem
plary topical skin composition , referred to as emulsion with
TABLE 22 retinal, can be found in Table 26 . The following steps are
Percentage of subjects showing improvement. taken to prepare the emulsion : 1 ) Prepare PHASE A under
propeller at medium speed . 2 ) Premix PHASE A1 and add
Skin Attributes Week 4 Week 8 PHASE A , mix and heat to 75º C . until uniform . 3 ) In
Global acne assessment 87 % 91 %
separate vessel, prepare PHASE B and heat to 75º C . 4 )
Papules 87 % 100 % When PHASE A and PHASE B reach 75° C ., add PHASE
Pustules (based on subjects that had 86 % 100 % B to PHASE A under homogenization . 5 ) Cool to 50° C . and
pustules at baseline ) add PHASE C , homogenize until uniform . 6 ) Cool to 40° C .
Open comedomes (based on subjects that 100 % 100 % and add PHASE D , homogenize until uniform . 7) In a
had open comedones at baseline) separate container, take 10 % of cream to well disperse
Closed comedones 83 % 83 %
Macules 51 % 48 % Hydroxysomes Retinaldehyde by mixing and homogeniz
ing . Hydroxysomes Retinaldehyde does not solubilize in the
formula, and the particles must be well evenly dispersed .
[ 0177 ] A comparison of treatment with the UNBLEMISH Transfer to main container and continue to homogenize and
Regimen and the UNBLEMISH Regimen plus the IRS well disperse .
demonstrated a clear improvement in acne grade when the
combination treatment was used . Table 23 shows the mean TABLE 26
percent change in acne grade .
Emulsion with Retinal
TABLE 23 PHASE INCI Concentration
Mean Percent Change in Acne Grade. Water 85 . 345 %
Week 2 Week 4 Week 6 / 8 A1 Xanthan gum
Glycerin
0 . 300 %
1. 000 %
UNBLEMISH Regimen 16 % 42 % 63 % Caprylic/Capric triglycerides 3 .000 %
UNBLEMISH Regimen + IRS 37 % 59 % 65 % Cetyl alcohol 2 . 000 %
Stearyl alcohol 2 .000 %
Glyceryl stearate and PEG -100 Stearate 1 .000 %
[0178 ] Table 24 provides the objective (clinical) assess Dimethicone 3 . 000 %
Polyacrylate- 13, polyisobutene, polysorbate-20 1 .000 %
ment of tolerability , all results at weeks 2 , 4 , and 8 fall into Phenoxyethanol and ethylhexylglycerin 1 . 000 %
the very mild or mild category and is considered tolerable . Retinal/ Retinaldehyde and hydroxyapatite 0 . 355 %
TABLE 24
Percentage of Subjects with Skin Ailment Compared to Baseline. Example 9 : Clinical Study Evaluating Efficacy and
Tolerance of IRS Compared with Adapalene Gel
Skin Ailment Week 2 Week 4 Week 8
Dryness 17 % 4% 0%
[0181 ] The objective of the study is to evaluate and
Peeling 13 % 4% 0%
compare the anti -aging efficacy and tolerability of 0 . 1 %
Erythema 9% 0% 0% Adapalene compared to Intensive Renewing Serum over a
Stinging 9% 9% 0% 12 -week period when used by women with mild to moderate
Itching 9% 9% 4% lines and wrinkles , dullness and moderate dyschromia .
Burning 4% 9% 4%
[0182 ] Subjects reported to the facility at Baseline for
Scaling 4% 0% 0%
Edema 0% 0% 0% Expert Grader assessments of various facial photoaging and
irritation parameters , subjective assessments of facial irrita
tion , digital imaging of the face, replica sampling of the
US 2019 /0099340 A1 Apr. 4 , 2019
crow ' s foot area , capacitance and firmness/ elasticity mea grading/Baseline aided , 15 . Pinch recoil (under the eye ):
surements of the face and completed a self -assessment Live grading (For this assessment, a 0 - 9 score will not be
questionnaire . Subjects were randomized to receive 1 of 2 assigned . Per the Sponsor, the evaluator will pinch the
investigational products for treatment to the entire face for subject 's skin at the designated site using the thumb and
12 weeks. Subjects returned to the lab at Week 2 and Week forefinger and hold the skin in place for approximately 2
4 to have Expert Grader assessments , digital imaging and seconds . A stopwatch will be started upon release and the
self-assessments repeated . At Weeks 8 and 12 , subjects time required for the subject's skin to return to its original
returned for Expert Grader assessments , digital imaging , conformation will be measured to the nearest tenth of a
replica sampling, capacitance and firmness/ elasticity mea second . A decrease in pinch recoil times over time indicates
surements and self -assessments . an improvement in skin “bounce-back " or elasticity / resil
[0183 ] Treatments & Procedures : iency .). For the above efficacy parameters , parameters that
[ 0184 ] Expert Grader Assessments: In addition to screen indicate live grades were completed at Baseline and after 2 ,
ing and selecting the final panel, an Expert Grader assessed 4 , 8 and 12 weeks of treatment. For the parameters that
the face of each subject for various irritation and efficacy indicate grading of photos , the grading was completed after
parameters at Baseline and after 2 , 4, 8 and 12 weeks of the conclusion of the study.
treatment. The scale that was used for each assessment [0188 ] Digital Photography: Digital images using visible ,
parameter (unless otherwise indicated ) is: O = none , cross -polarized , parallel, and UV lighting were taken ofeach
1 -3 = mild , 4 -5 = moderate , 7 - 9 = severe . subject' s face using a custom photography system . Images
10185 ) Irritation parameters: The Expert Grader assessed were taken of each subject's face (Left, Right and Center
the face of each subject at each time point for the following views) at Baseline and again after 2 , 4 , 8 and 12 weeks of
irritation parameters using a 0 -9 scale : Erythema, Dryness , treatment.
Scaling, and Edema. Using a 0 - 9 scale , subjects were asked [0189 ] Skin Surface Impressions: Silflo impressions of the
to rate their amount of: Burning , Stinging , Itching , Tight left crow ' s foot area were made by a trained cyberDERM
ness , and Dryness . technician at Baseline ( prior to treatment) and again after 8
[ 01861. Efficacy parameters: The assessments of efficacy and 12 weeks of treatment. The sampled site on each
were made using methods that would provide the Sponsor individual subject was delineated by affixing an adhesive
the most information on changes in the subject' s skin over ring using extreme care not to alter the surface tension across
time. The methods that the Expert Grader used to assess the skin . Skin impressions were obtained with silicon dental
efficacy are as follows: 1 . Live Grading: Absolute scores impression material. A thin layer of freshly prepared mate
from viewing the subject's face were assigned using a 0 - 9 rial was gently spread over the bounded area of the ring
scale . Live grades were conducted at each time point . 2 . using a stainless steel spatula . Within 2 to 3 minutes , the
Baseline Aided Grading: Absolute scores from viewing the material should polymerize after which time the ring
subject ' s face were assigned using a 0 - 9 scale at the Baseline together with the impression was lifted from the skin . Each
visit and the ExpertGrader used the subject ' s Baseline photo specimen was immediately coded as to subject, time point
for reference at follow -up visits . Baseline aided grading was and test site . A Digital Image Analysis System consisting of
conducted at each time point other than at Baseline . 3 . Visioline VL 650 hardware (Courage +Khazaka , Cologne ,
Comparison Grading from Photos: Comparison grading was Germany ) with a specialized image analysis software pack
performed after the conclusion of the study. The Expert age (Image -Pro Premiere ) was used . The resulting images
Grader compared the photos from each time point to Base consisted of a series of shadows that directly corresponded
line for improvement/worsening using the below scale : to the pattern ofwrinkles . During analysis, one can measure
- 4 = Marked worsening , - 3 =Moderate worsening , - 2 = Mild changes in skin surface topography by selecting a gray level
worsening, - 1 = Barely perceptible worsening, - 0 . 1 = Forced threshold that allows one to directly determine the projected
choice worsening , O = No change, 0. 1 = Forced choice area of the shadowed region associated with the wrinkles .
improvement, 1 = Barely perceptible improvement, 2 = Mild Changes in skin surface topography can be quantified by
improvement, 3 = Moderate improvement, and 4 =Marked measuring the dimensions of the individual shadows as well
improvement. as the overall area of shadowing .
[0187 ] The following efficacy parameters were assessed [0190 ] Corneometer® CM 825: All measurements were
by the Expert Grader along with the assessment method (s ) taken following a minimum 25 -minute acclimation period in
are listed : 1. Skin Texture ( softness/ smoothness ) [tactile ]: a controlled environment with the relative humidity main
Live grading, 2 . Skin Texture [ visual]: Live grading /Base - tained at less than 50 % and temperature maintained at
line aided , 3 . Fine Lines (eye area including crow ' s feet): 19 - 22° C . Themeasuring principle of the Courage + Khazaka
Live grading/ Baseline aided /Comparison scores from pho Corneometer® CM 825 is based on capacitance measure
tos, 4 . Wrinkles ( eye area , including crows feet): Live ment of a dielectric medium . Any change in the dielectric
grading , Baseline aided , Comparison scores from photos, 5 . constant due to skin surface hydration variation alters the
Pore appearance: Comparison scores from photos, 6 . Firm capacitance of a precision measuring capacitor. The mea
ness : Live grading, 7 . Sagging (nasolabial fold area ): Com surement can detect even slight changes in the hydration
parison scores from photos, 8 . Discrete hyperpigmentation : level. The reproducibility of the measurement is very high
Comparison scores from photos, 9 . Mottled hyperpigmen and the measurement time is very short ( 1 s ). The instrument
tation : Comparison scores from photos , 10 . Skin tone even technician took five measurements from the left and right
ness: Comparison scores from photos, 11 . Radiance /lumi sides of the face at the nexus where a line drawn lateral from
nosity /glow (defined as Dull to luminous /shiny ) : Live the nostril meets a line drawn vertical from the corner of the
grading, 12 . Sallowness (sallow to rosy ) : Live grading/ eye at Baseline ( prior to treatment ) and again after 8 and 12
Baseline aided , 13 . Overall healthy skin appearance: Com weeks of treatment. The average value was computed for
parison scores from photos, 14 . Overall photodamage : Live each site after each measurement session .
US 2019 / 0099340 A1 Apr. 4 , 2019
[0191] DermaLab® Suction Cup : All measurements were [0197 ] Investigational Products : The following investiga
taken following a minimum 25 -minute acclimation period in tional products (test product and benchmark ) were supplied
a controlled environment with the relative humidity main by the Sponsor and were labeled as follows:
tained at less than 50 % and temperature maintained at [0198 ]. Product C : REDEFINE Intensive Renewing
19 -22° C . A DermaLab® USB with a Suction Cup was used Serum ,
to evaluate skin elasticity. The suction probe which was [0199 ] Product N : Differin 0 . 10 % Adapalene
placed on the test site is capable of producing a vacuum up [0200 ] Treatment Procedures: approximately 20 -25 sub
to 650 mbar . Within the suction chamber there is a height jects assigned to each product per randomization . After the
detection system to measure how much the skin has moved Baseline assessments and measurements had been com
as a result of the applied vacuum . Themeasuring aperture is pleted , the subjects reported to the Treatment Technician ,
10 mm in diameter and the probe itself has an ultra low who dispensed a new container of their assigned product to
weight of approximately 7 g for minimum skin bias. The the subject and instructed the subject to apply the product
probe was secured to the panelist ' s site using an adhesive according to the Sponsor 's instructions below :
ring . When the suction pump is activated it creates a vacuum 10201 ) Product C : Morning instructions: Follow your
that draws the skin into the chamber and the height to which regular morning skincare routine . Evening instructions :
the skin is drawn in is recorded in the software and used to Product C should be used once daily in the evening, after
calculate elasticity parameters . The skin is then allowed to your regular cleanser. Open a capsule by twisting off the tail
relax for 1 second before the vacuum resumes for a total of end of one capsule . Apply the serum over your entire face ,
5 cycles . Parameters related to elasticity and firmness were including under the eyes and crow ' s feet. Do not apply on
reported . The instrument technician took one measurement eyelids. Avoid getting into eyes, In case of inadvertent eye
from the left and right sides of the face at the nexus where contact, rinse eyes with plenty of water to remove product
a line drawn lateral from the nostril meets a line drawn from eyes. Do not wash off from skin . Use one capsule per
vertical from the corner of the eye at Baseline (prior to night. Follow with the rest of your evening skin care
treatment ) and again after 8 and 12 weeks of treatment. Regimen . Note :make sure that no water gets into the jar and
[0192] Self - Assessment Questionnaires: Subjects com that your hands are dry before use. Please ensure the jar is
pleted Sponsor -supplied self-assessment questionnaires tightly closed after each use .
( Appendix D ) at Baseline and after 2 , 4 , 8 and 12 weeks of [0202] Product N : Morning instructions: Follow your
treatment. regular morning skincare routine . Evening instructions :
[0193] Baseline Questionnaire included questions about Product N should be used once daily in the evening, after
skin type , the frequency of acne pimples or breakouts , types your regular cleanser. Clean the skin gently with your
and names of products used in their regular skincare routine , regular cleanser and pat dry before applying Product N .
effects of other products on skin . Cover the entire face , including under the eyes and crow ' s
[ 0194 ] Week 2 Questionnaire included questions about feet, with a thin layer. Do not apply on eyelids. Avoid
what the subject liked and disliked about the test product, if product contact with eyes, lips and mouth . If contact occurs ,
the subject experienced any irritation (burning, stinging, immediately flush the area with water. Do not wash off.
itching, tightness, dryness, redness, etc.) while using the test Wash hands after use . Do not use more than one time a day .
product for the past 2 weeks. Follow with the rest of your evening skin care Regimen .
[0195 ] Week 4 Questionnaire included questions about 0203 ] The results of the tolerability assessments demon
what the subject liked and disliked about the test product, if strates Intensive Renewing Serum was well tolerated and
the subject experienced any irritation (burning , stinging , more tolerated than Adapalene. These assessments were
itching , tightness , dryness , redness , etc .) while using the test measured subjectively and objectively as described above .
product for the past 2 weeks , and was asked to rate the level [0204 ] Subjective Results — Burning : somewhat greater
of agreement with the following statements compared to degree of perceived burning with Adapalene, Stinging:
starting the study (baseline): a . Skin looks healthier , b . Skin somewhat greater degree of perceived stinging with Ada
feels healthier, c . My skin looks clearer, d . Pores appear palene, Itching: little to no difference in perceived itching
smaller, e . I experienced fewer pimples /breakouts , f Skin between products, Dryness/ Tightness: slightly greater per
feels firmer, g . Skin 's texture looks smoother, h . Age spots / ception of dryness/tightness with Adapalene , most notably at
darks spots are less visible , i. Skin ' s texture is visibly more Week 4 .
even , j. Skin feels smoother, k . Skin is visibly more radiant, [0205 ] Objective (Clinical) Results — Erythema: some
1 . Skin looks visibly younger, m . Skin feels younger, n . Skin what greater degree of erythema with Adapalene , Dryness :
tone /color is visibly more even , o . I see fewer lines/wrinkles , greater degree of tactile dryness with Adapalene, Scaling:
p . The product reduced the appearance of nose to mouth greater degree of visual scaling with Adapalene, Edema:
lines (nasolabial folds), q . Skin is visibly less red , r. Oily and little or no edema with both products .
dry patches feel more balanced , s .Makeup stays fresh all [0206 ] FIG . 4A (IRS) and FIG . 4B (adapalene ) graphically
day after using the product, t. Makeup goes on much better depict tolerability results at week 2 . FIG . 5A (IRS ) and FIG .
after using the test product , u . I like the overall appearance 5B (adapalene ) graphically depict tolerability results at week
ofmy skin , v. The test product did not leave my skin feeling 4 . FIG . 6A (IRS ) and FIG . 6B (adapalene ) graphically depict
tight or uncomfortable, w . I liked using the test product tolerability results at week 8 . FIG . 7A ( IRS ) and FIG . 7B
nightly, and x . I liked using the test product. (adapalene ) graphically depict tolerability results at week
[0196 ] Weeks 8 and 12 Questionnaires included questions 12 . Parameters listed above dotted line = subjective assess
similar to the week 4 questionnaire , as well as whether the ment, below dotted line = clinical ( objective ) assessment.
subject was satisfied with their results and would they [0207] The results of the clinical grading assessment of
continue to use the product and recommend product to a efficacy demonstrate that, in terms of mean % change from
friend. baseline, Intensive Renewing Serum performed slightly
US 2019 /0099340 A1 Apr. 4 , 2019
22
better than Adapalene. FIGS. 8 (week 2 ), 9 (week 4 ), 10 improvement by week 12 with IRS ; Mottled Hyperpigmen
(week 8 ), and 11 (week 12 ) graphically depict incidence of tation: slight improvement by week 8 with IRS . A progres
improvement results. sive & slightly better result with Adapalene; Skin Tone
Evenness : slight, progressive improvement by week 4
[0208 ] Skin Texture ( Tactile ): slight improvement with through week 12 with both products; Overall Healthy Skin
IRS by week 8 thru week 12 . By week 12 , no improvement Appearance : slight, progressive improvement by week 4
with Adapalene ; Skin Texture ( Visual) : slight improvement
with IRS and Adapalene by weeks 8 & 12 ; Fine Lines: both through week 12 with both products; Pore Appearance : no
were comparable first 4 weeks with mild improvements by change for either product ; and Sagging : no change for either
week 8 , IRS continues to improve through week 12 , while product.
Adapalene remains constant; Wrinkles : little or no change in [0211 ] Table 27 provides the results of the self -assessment
mean scores for both products ; Firmness ( Tactile ): mild questionnaires, which provided information regarding the
increase in firmness for both by week 12 ; Radiance/Lumi subject 's overall experience with the products . Subjects
nosity /Glow : mild progressive improvement throughout 12
weeks with IRS, Mild improvement persists through week 8 using the Intensive Renewing Serum were much more
with Adapalene; Sallowness : mild improvement for both satisfied with their results after 12 weeks.
TABLE 27
Summary of User Experience
Week 4 Week 8 Week 12
% % 0%
% agreement % agreement % agreement
agreement for agreement for agreement for
Statement for IRS adapalene for IRS adapalene for IRS adapalene
I liked using 57 96 87
the test
product
I liked using
the test
87 61 65 96 50
product
nightly
The test 61 35 7050 83
product did
not leave my
skin feeling
tight or
uncomfortable
Makeup stays
fresh all day
61
61 26
26
57 40
40
61
61
after using the

product
Makeup goes 5226 612570 30.
on much
better after
using the test
product
I want to
continue
70
using this
product
I would
recommend - - 87 70 87
87
this product to
a friend
products ; Overall Photodamage : no change in mean scores Example 10 : Clinical Study of the Safety and
for both products; and Elasticity /Resiliency : slight improve Efficacy of IRS for Acne
ment with IRS by weeks 8 & 12 , No improvement with
Adapalene . 0212 ] The objective of this study was to evaluate the
[ 0209] The results of the photo comparison demonstrates efficacy and tolerance of the Intensive Renewing Serum with
the mean scores slightly favored Adapalene over Intensive a skin care regimen when used by women with mild to
Renewing Serum . FIGS. 12 (week 2 ), 13 (week 4 ), 14 (week moderate acne vulgaris over a twelve week time period .
8 ), and 15 (week 12 ) graphically depict incidence of [0213 ] This was a single center, single cell (target comple
improvement results . tion n = 25 ), non -randomized 12 week clinical study of
[0210 ] Fine Lines: slight improvement by week 12 for female subjects ages 22 -45 years of age with a Fitzpatrick
both products ; Wrinkles: slight, progressive improvement Skin Type of I-VI with mild to moderate acne vulgaris
through week 12 for both products ; Discrete Hyperpigmen (defined by an IGA score of 2 - 3 ) on the face with a minimum
tation : slightly better results with Adapalene . Little or no of 5 inflammatory lesions (jawline to hairline ), mild to
US 2019 / 0099340 A1 Apr. 4 , 2019
23
moderate skin clarity (defined by a score of 3 -6 on a 0 - 9 (similar size to the eraser on a pencil ) on the skin . No pain ,
scale ) andmild to moderate crow ' s feetwrinkles ( defined by discomfort, or known documented ill effects were associated
a score of 1 -6 on a 0 - 9 scale ). A minimum of 50 % of subjects with this procedure . The Week 8 measurements was taken at
had a moderate degree of crow ' s feet wrinkles (defined by about the same time ( + / - 3 hours ) as the Baseline visit to
a score of 4 -6 on a 0 - 9 scale ) and this group of subjects assure the same level of sebaceous gland activity .
underwent analysis skin surface impressions and ultrasound 0220 ] Ultrasound Measurements: At the Baseline visit 15
measurements . subjects were chosen by the Principal Investigator who had
[0214 ] Clinical Evaluations: At the Baseline , Week 2 , moderate crow 's feet wrinkles ( score of 4 -6 on a 0 - 9 scale )
Week 4 , Week 8 , and Week 12 visits the Principal Investi to have Ultrasound measurements performed of both left and
gator assessed the following clinical grading parameters: right crow ' s feet areas at the Baseline and Week 8 visits . The
[0215 ] 1. Investigator Global Acne Assessment Score : Ultrasound Echography was used to measure the skin thick
O = Clear, residual hyperpigmentation and erythema may be ness . This was done with a DermaScan C (Cortex Technol
present; 1 = Almost clear, a few scattered comedones and a ogy , Hadsund , Denmark ). This consisted of a hand held
few ( less than five ) small papules ; 2 = Mild , easily recogniz probe that contained an ultrasonic transducer which was
able ; less than half the face is involved , many comedones interfaced to a specially configured computer. The probe had
and many papules and pustules ; 3 = Moderate ,more than half a built - in closed water path and was capable of scanning an
of the face is involved , numerous comedones, papules , and area of the skin surface 12 .1 mm in length . To ensure good
pustules ; 4 = Severe , entire face is involved , covered with transmission of the ultrasound signals , a water compatible
comedones, numerous papules and pustules, and few nod ultrasound gel (Dane Gel, cyberDerm , Inc . Broomall , Pa.)
ules and cysts ; 5 Very severe , highly inflammatory acne was used as a skin contact medium . The scanner processed
covering the face ; with nodules and cysts present. four frames per second and displayed the results as a
0216 ] 2 . Global Lesion Count: At the Baseline, Week 2 , live - B -mode image . A standard medium focus 20 MHz
Week 4 and Week 8 visits each subject had their inflamma transducer with maximum focal distance of 13 mm was
tory lesions (papules and pustules ) and non-inflammatory employed . With this transducer, the axial system resolution
lesions (open and closed comedones) and macules (PIH / was 60 um and the lateral system resolution was 150 um .
PIE ) separately counted and recorded for their forehead , left Gain settings were selected that produced the best visual
cheek , chin ( including the area above the upper lip ), and ization of the test site, this gain setting was recorded for each
right cheek . The counts in each section were added up to person and was used for subsequent visits so changes in echo
give a total lesion count number. strength could accurately be evaluated .
[0217 ] 3 . Clinical Grading Parameters: At the Baseline , 10221 ] Cutometer Measurements : At the Baseline, Week 4
Week 2 , Week 4 , Week 8 and Week 12 visits clinical grading and Week 8 visits all subjects had a single cutometer
parameters (Overall Healthy Appearance of Skin Condition , measurement conducted on the right ocular bone directly
Even Skin Tone , Skin Texture * , Global Fine Lines, Pore beneath the center of the eye . The cutometer measured
Appearance , Global Wrinkles, Skin Clarity , Fine Lines elasticity (skin firmness ) of the upper skin layers using a
Crow ' s Feet and Under Eye , Radiance , Coarse Wrinkles negative pressure that was created in the device and applied
Crow ' s Feet and Under Eye , Oiliness , Overall Photodam perpendicularly to the skin surface; in the time strain mode,
age , Plumpness/ Fullness, Skin Firmness * [* assessed by skin was drawn in to the aperture of the probe by a constant
touch ]) were assessed using a 0 - 9 modified Griffiths scale vacuum that was applied to the skin surface fir a defined time
where ( = none , 1 -3 =mild , 4 -6 =moderate and 7 - 9 = severe . In and then the vacuum was reduced to Ombar so the skin could
addition , sub - orbital skin elasticity was assessed via pinch return to its original shape. The penetration depth of the skin
recoil measurement. The Principal Investigator gently in the probe was measured by a non -contact optical mea
pinched the skin of the subject's lower eyelid using the suring system . Extensibility (RO ) , resiliency (R2 ), pure
thumb and forefinger. The Principal Investigator held the elasticity (R5), and biological elasticity (R7) parameters
skin in place for approximately 3 seconds. A decrease in were all recorded for each subject.
pinch -recoil times indicated an improvement in skin elas 0222 ] Corneometer Measurements : At the Baseline .
ticity /resiliency . The pinch -recoil response was graded on a Week 2 , Week 4 and Week 8 visits all subjects had corne
0 - 9 scale where ( = none , 1- 3 = mild skin laxity , 4 -6 = moderate ometer measurements of the left cheek . The corneometer
skin laxity , and 7 - 9 = severe skin laxity . was used to measure the moisture content of the skin . This
[0218 ] 4 . Clinical Tolerance Scores and Safety Endpoints: measurement was performed by having a small open probe
At the Baseline , Week 2 , Week 4 , Week 8 and Week 12 visits placed on the skin surface . Three single readings were taken
the following parameters were assessed by the Principal per subject on the center of the left cheek (at the intersection
Investigator or by the subject (via interview by the Principal of lines extending up from the corner of the mouth and
Investigator ) using a 0 -3 scale where O = None, 1- 1.5 =Mild , horizontally across the bottom of the nose ) at each visit .
2 - 2 .5 = Moderate and 3 - 3 .5 = Severe ). Principal Investigator: [0223] Skin Surface Impressions: At the Baseline, Week 8
erythema, edema, dryness, scaling , and peeling. Subject: and Week 12 visits skin surface impressions ( replicas ) were
burning/ itching , itching, and tightness . performed on both left and right crow ' s feet areas on up to
[0219 ] Sebumeter Measurements : At the Baseline, and 15 subjects chosen by the Principal Investigator at Baseline.
Week 8 visits a Sebumeter was used to assess sebum Silflo impressions performed at each visit. The skin impres
quantities on the skin surface ( skin oiliness ). The Sebumeter sions were obtained with silicone dental impression mate
used grease spot photometry for the qualification of sebum . rial . A thin layer of freshly prepared material was gently
A single reading was taken from all subjects at the center of spread over the bounded area of a ring using a stainless steel
the forehead and on the center of the left cheek (to measure spatula. The material polymerized after about 2 -3 minutes
outside the T -zone area ). The same placement was used for after which the ring together with the impression was lifted
all readings for each subject by placing a small probe from the skin . Each specimen was immediately coded with
US 2019 / 0099340 A1 Apr. 4 , 2019
24
the subject 's number, time point and test site, then stored for [0224 ] Subject Questionnaires: At Baseline , Week 2 , Week
analysis . A Digital Image Analysis System consisting of 4 , Week 8 and Week 12 visits, subjects completed a self
Visioline VL 650 hardware (Courage + Khazaka , Cologne , assessment questionnaire while seated in front of a mirror.
Germany) with a specialized image analysis software pack [0225 ] Study Products : 1. Wash (UNBLEMISH Acne
age (Image - Pro Premiere ) was used for impression analysis. Treatment Sulfur Wash ), 2 . Toner (UNBLEMISH Clarifying
This system consisted of a high resolution black and white Toner ), 3 . Treatment (UNBLEMISH Dual Intensive Acne
video camera interfaced with a computer. An LED illumi Treatment) , 4 . SPF (UNBLEMISH oil Control Lotion SPF
nator was used to cross illuminate the specimen perpendicu
lar to the major lines which accentuated the surface details . 20 ), 5 . Hydration Serum ( ENHANCEMENTS Active
Images were made with the illuminator at a fixed angle and Hydration Serum ), 6 . Night serum (REDEFINE Intensive
distance while the specimen was positioned on a turntable . Renewing Serum ).
The resulting images consisted of a series of shadows that [0226 ] Product Application : Each subject received a skin
directly corresponded to the pattern of wrinkles . During the regimen (Wash , Toner , Treatment, and SPF ) and a Night
analysis the changes in the skin surface topography were Serum at the Baseline visit for daily morning and evening
measured by selecting a gray level threshold that allowed the applications for 12 weeks . Subjects received a Hydration
projected area of the shadowed region associated with the Serum for evening applications Weeks 9 - 12 . Subjects
wrinkles to be directly determined . Changes in the skin applied the skin regimen to their full face following the
surface topography were quantified bymeasuring the dimen instructions . Both written and verbal instructions were pro
sions of the individual shadows as well as the overall area of vided to each subject prior to their first application .
shadowing. [0227 ] Results are provided in Tables 28 - 31 .
TABLE 28
Summary of Results - Change from Baseline
Assessment Week 2 Week 4 Week 8 Week 12
Overall healthy 43 % improve 83 % improve 87 % improve 91 % improve
appearance of skin 57 % same 17 % same 17 % same 9 % same
condition
Skin Texture 91 % improve 100 % improve 100 % improve 100 % improve
(tactile ) 9 % same
Pore appearance 39 % improve 48 % improve 57 % improve 57 % improve
61 % same 52 % same 43 % same 43 % same
Skin clarity 74 % improve 91 % improve 100 % improve 100 % improve
26 % same 9 % same
Radiance 35 % improve 65 % improve 91 % improve 91 % improve
4 % worse
Oiliness 91% improve 96 % improve 96 % improve 100 % improve
9 % same 4 % same 4 % same
Plumpness/ 4 % improve 35 % improve 70 % improve 78 % improve
Fullness (Visual) 96 % same 65 % same 30 % same 22 % same
Even skin tone 22 % improve 57 % improve 70 % improve 74 % improve
Global fine lines 4 % improve 17 % improve 26 % improve 30 % improve
Global wrinkles 4 % improve 22 % improve 30 % improve 35 % improve
Fine lines- Crow 's 17 % improve 30 % improve 35 % improve 52 % improve
feet and under eye 83 % same 70 % same 65 % same 48 same
Coarse lines 9 % improve 22 % improve 22 % improve 30 % improve
Crow 's feet and 87 % same 74 % same 74 % same 65 % same
under eye 4 % worse 4 % worse 4 % worse 4 % worse
Overall 4 % improve 17 % improve 30 % improve 43 % improve
photodamage 96 % same 83 % same 70 % same 57 % same
Skin firmness 9 % improve 9 % improve 22 % improve 26 % improve
(tactile ) 91 % same 91 % same 78 % same 74 % same
Pinch Recoil 13 % improve 13 % improve 13 % improve 13 % improve
( Elasticity / 87 % same 87 % same 87 % same 87 % same
Resiliency )
Erythema 91 % same 100 % same 100 % same 100 % same
9 % worse
Dryness 83 % same 96 % same 100 % same 100 % same
17 % worse 4 % worse
Scaling 96 % same 100 % same 100 % same 100 % same
4 % worse
Peeling 87 % same 96 % same 100 % same 100 % same
4 % worse
Burning 96 % same 100 % same 4 % improve
4 % worse 96 % same
Stinging 9 % improve 9 % improve 9 % improve
83 % same 91 % same 91 % same
9 % worse
US 2019 / 0099340 A1 Apr. 4 , 2019
25
TABLE 28 - continued
Summary of Results - Change from Baseline
Assessment Week 2 Week 4 Week 8 Week 12
Itching 96 % same 100 % same 4 % improve
4 % worse 96 % same
TABLE 29 TABLE 31 -continued

IGA and Lesion Count % Change from Baseline Self-Assessment Questionnaire Data
Summary - % Change form Baseline
Assessment Week 2 Week 4 Week 8
Question Week 2 Week 4 Week 8 Week 12
Investigator Global - 37 % - 59 % - 65 % Appearance of 90 % 105 % 132 % 147 %
Acne (IGA ) Pimples /Breakouts
Inflammatory Lesions -45 % - 65 % - 82 % Number of 77 % 76 % 99 % 113 %
Non -inflammatory - 12 % - 30 % - 27 % Pimples /Breakouts
lesions Size of 52 % 53 % 69 % 76 %
Macules - 22 % - 16 % 13 % Pimples /Breakouts
Severity of 52 % 56 % 71 % 83 %
Pimples/ Breakouts
Oiliness of skin 38 % 60 % 75 % 59 %
Skin Moisturization 8% 16 % 41 % 32 %
TABLE 30 Appearance of Redness 28 % 44 % 69 % 77 %
Associated with
Instrument Data Summary - % Change from baseline Pimples /Breakouts
Skin Clarity / 36 % 46 % 78 % 79 %
Assessment Week 2 Week 4 Week 8 Translucency
7% Appearance of pores 35 % 35 % 51 % 55 %
Corneometer 1% 22 %
Overall skin appearance 47 % 54 % 79 % 88 %
Left Cheek
Average Overall Skin condition 56 % 58 % 80 % 90 %
Cutometer - 16 % -9%
Skin looks healthy 45 % 51 % 74 % 72 %
Extensibility Skin feels healthy 38 % 37 % 58 % 67%
Right
Cutometer -4 % 3% 0228 ] Conclusion : Twenty three ( 23 ) subjects aged 22 to
Resiliency
Right 45 years completed this twelve ( 12 ) week study ( target
Cutometer 7% 8% accrual was twenty five). All received a skin care regimen
Pure elasticity (Wash , Toner, Acne Treatment, and SPF ) plus serums (Night
Cutometer 2% 5% and Hydration ). Statistically significant improvement and
Biological
Elasticity tolerability was demonstrated over the twelve ( 12 ) week
Sebumeter - 18 % study period .
Center of
Forehead
[0229 ] Acne improved significantly with reduction of IGA
Sebumeter -2 % and Inflammatory & Non - Inflammatory Lesion Counts . Sta
Center of Left tistically significant improvement of IGA was seen as early
cheek as Week 2 . Inflammatory Lesion Counts and Non -inflam
matory Lesion Counts demonstrated statistically significant
reduction by Week 2 and Week 4 , respectively .
TABLE 31 [0230 ] All clinical grading parameters demonstrated sta
tistically significant improvement except Pinch Recoil .
Self- Assessment Questionnaire Data Eight (8 ) of fifteen ( 15 ) parameters demonstrated statisti
Summary - % Change form Baseline cally significant reduction (improvement ) as early as Week
Question Week 2 Week 4 Week 8 Week 12 2 and four (4 ) of fifteen (15 ) by Week 4 . Statistically
significant improvement was seen in Skin Firmness and
Appearance of 21 % 25 % 29 % 42 % Crow 's Feet & Under-eye Course Lines by Week 8 and
hyperpigmentation / Week 12 , respectively .
pigmentation
discoloration 10231 ] Corneometer measurements from the central and
Skin firmness -4% 4% 16 % 6% left cheek demonstrated statistically significant improve
Skin texture
Skin radiance /
7%
26 %
14 %
27 %
1950%
45 %
32 %
60 %
ment in moisture content ( hydration ) at Week 8 . Cutometer
luminosity / glow measurements from the right suborbital face demonstrated
Appearance of lines/ 3% 1% 15 % 21 % improvement in elasticity (skin firmness ) measurements .
wrinkles While Pure and Biological Elasticity demonstrated improve
Skin softness -4 % 4% 15 % 19 % ment, Extensibility achieved statistically significant
Skin Plumpness 2% 10 % 21 % 21 % improvement as both Week 2 and Week 4 .Minimal changes
Skin suppleness 7% 10 % 20 % 28 %
Skin Tone evenness 23 % 28 % 53 % 69 % were seen for Resiliency . Sebumeter measurements from the
Acne breakouts 92 % 95 % 111 % 135 % central forehand and left cheek demonstrated 18 % and 2 %
sebum reduction at Week 8 , respectively . These changes
US 2019 / 0099340 A1 Apr. 4 , 2019
were not statistically significant. Image analysis of Skin retinoic acid at 5 uM . Table 32 presents the effect of test
Surface Impressions (replicas ) of the crow 's feet areas materials on RARE -mediated gene expression as % for all
demonstrated statistically significant reduction in Shadow experimental conditions.
Area (lines ) at Week 8 ( 24 % reduction ) and Week 12 ( 33 %
reduction ). Ultrasound measurements of the crow ' s feet TABLE 32
areas showed no statistically significant changes in Thick
ness and Intensity at Week 8 and Week 12 compared to Effect of test materials on the RARE-mediated firefly luciferase
expression expressed as % water control and fold change vs. water.
baseline. P value was calculated using two- tailed Student test.
[0232] Product-related skin irritation was reported by one Test Material % control P value Fold increase
subject who did not complete the study and statistically
significant Dryness and near statistically significant Peeling Water 100 1 .000 1 .000
was noted at Week 2 . For the remainder of the 12 week 0 . 4 % DMSO 97 0 .815 0 .97
study, clinical tolerance scores demonstrated no statistically 5 UM ATRA 973 0 .000 9 .7
significant changes . 1 uM ATRA 1054 0 .000 10 .5
0 .2 UM ATRA 775 0 .000
[ 0233] Subject Questionnaire responses revealed statisti 10 UM Retinol 278 0 .000
cally significant favorable responses in the majority of 5 UM Retinol 268 0 .000
1 uM Retinol 138 0 .001
questions . 10 UM Vit A Palmitate 86
77
0 .086 ta
[0234 ] In summary , the treatment regimen plus serums 5 uM Vit A Palmitate 0 .043 0 .8
1 uM Vit A Palmitate 0 .007 0 .7
significantly improved acne and appearance and was well 10 UM Retinal 946 0 .000 9 .5
tolerated . 5 UM Retinal 1005 0 . 000 10 .0
1 uM Retinal 613 0 .000 6 .1
10 UM NEAR - 1 586 0 .000 5 .8
Example 11: Effect of 6 Test Materials on the
Activation of Retinoic Acid Response Element
(RARE ) Transcription Factor Pathway
[ 0235 ] Objective : Retinoic Acid Receptor (RAR ) controls
5 UM NEAR - 1
1 uM NEAR - 1
10 UM Retinoid Ester
5 uM Retinoid Ester
1 uM Retinoid Ester
652
461
281
230
147
0 .000
0 .000
0 .000
0 .000
0 . 001
ON Uwdau
1 UM ATRA 1284 0 .000 12 . 8
gene transcription by binding to Retinoid Acid Response 0 .2 UM ATRA 1099 0 .000 11. 0
Elements (RAREs ) in DNA . This process is modulated by 10 UM Retinol 294 0 .000 2. 9
all trans retinoic acid (ATRA ) — a compound with well 5 UM Retinol 253 0 .000 2 .5
established anti -aging skin benefits. Despite these benefits 1 uM Retinol 150 0 .001 1.5
10 UM Vit A Palmitate 67 0 .006 0 .7
ATRA also exhibits undesirable side effects, and the discov 5 UM Vit A Palmitate 0 .004 0 .7
ery of ATRA functional analogues with improved therapeu 1 uM Vit A Palmitate 76 0 .012 0 .8
tic and /or cosmetic activity profile is highly desirable . Cig
nal RARE Reporter Assay® is designed to screen for such
compounds using cell cultures . The objective of this project
was to test 6 compounds (retinoic acid (ATRA ), retinol, Example 12 : Effect of 4 Test Materials on the
vitamin A palmitate, retinal, 10 % w /w Near- 1 in dimethyl Activation of Retinoic X Receptor Transcription
isosorbide , and 10 % w / w retionoid ester in dimethylisosor Factor Pathway
bide ) for the ability to activate RARE in this Cignal RARE [0238 ] Objective: Retinoid X receptors (RXRs) are one
Reporter Assay model . class of nuclear receptors through which retinoids mediate
[ 0236 ] Materials & Methods: The experiments were per their biological effects. These receptors function as tran
formed using HEK293 cells (Sigma, St. Louis , Mo.; cat. scription factors by binding as heterodimers to specific
# 85120602) seeded at 50 ,000 per well in a 96 well black sequences in the promoters of target genes . The protein
wall tissue culture plate . Cells were transfected by mixing encoded by this gene is a member of the steroid and thyroid
Cignal Reporter Assay firefly /renilla luciferase constructs hormone receptor superfamily of transcriptional regulators .
( cat. # CCS -016L ; Qiagen ) with Attractene Transfection One of its ligands is all trans retinoic acid (ATRA ) - a
Reagent (Qiagen ) in Opti-MEM supplemented with 1 % compound with well - established anti-aging skin benefits .
MEM Non -essential amino acid solution without L - gluta Despite these benefits ATRA also exhibits undesirable side
mine . After medium change test materials were added and effects, and the discovery of ATRA functional analogues
their effect on RARE induction was quantified 24 h later with improved therapeutic and /or cosmetic activity profile is
with the Dual-Luciferase Reporter Assay System (cat .# highly desirable . Cignal RXR Reporter Assay® is designed
E1960 ; Promega ). to screen for such compounds (retinoic acid (ATRA ), retinal,
[ 0237] Results and Discussion : RARE-mediated 10 % w / w Near - 1 in dimethylisosorbide , and 10 % w / w
luciferase expression for each experimental condition mea retionoid ester in dimethylisosorbide ) using cell cultures.
sured in chemoluminescence units and as fold change vs . The objective of this project was to test four compounds for
water control showed statistically - significant increase for all the ability to activate RXR in this Cignal RXR Reporter
ATRA concentrations, which provided technical validation Assay model.
of the experiment. All test materials except Vit- A -Pal were [0239 ] The experiments were performed using HEK293
active with Retinal being the best performer, followed by cells ( Sigma, St. Louis , Mo., cat.# 85120602) seeded at
Near - 1 . As determined by the Renilla readings , none of the 50 , 000 per well in a 96 well black -wall tissue culture plate .
compounds were toxic at the tested concentrations. Overall , Cells were transfected by mixing Cignal RXR Reporter
retinal is 1 . 7 times less effective than retinoic acid in Assay firefly / renilla luciferase constructs ( cat.# CCS9044L ;
modulating the RARE pathway at 1 uM , equivalent to Qiagen ) with Attractene Transfection Reagent (Qiagen ) in
US 2019 / 0099340 A1 Apr. 4 , 2019
27
Opti-MEM supplemented with 1 % MEM Non -essential Example 13 : Assessment of the

amino acid solution without Lglutamine. After medium Melanin -Modulatory Effect of Four Test Materials
change test materials were added and their effect on RXR and of their Skin Irritation Potential in
induction was quantified 24 h later with the Dual-Luciferase MelanoDermTM Skin Substitutes
Reporter Assay System (cat.# E1960 ; Promega ). [0243 ] Objective : The objective of this assay was to deter
[0240 ] RXR is a mixture of an inducible retinoid X mine the ability of the test materials (dimethylisosorbide
receptor responsive firefly luciferase construct and a con [DMI], retinoic acid [ATRA ], 10 % w / w NEAR - 1 in dim
stitutively expressing Renilla construct, which acts as an ethylisosorbide [NEAR - 1 ], Niacinamide PC (NAD ), and
internal control for normalizing transfection efficiencies and Kojic Acid [KA ]) and combinations thereof to inhibit mela
monitoring cell viability. Signal quantification was obtained nin production in MelanoDermTM skin substitute model. The
with ThermoFisher Scientific Luminoskan Ascent effect of these experimental conditions on the secretion of
Microplate Luminometer. the proinflammatory cytokine IL - 8 was also assessed, as a
[0241] Results and Discussion : Results of RXR -mediated surrogate for skin irritation potential.
luciferase expression for each experimental condition mea [0244 ] Tissues were equilibrated at 37° C . for 60 min . and
sured in chemoluminescence units , as fold change vs. water undiluted samples (25 ul) of test materials were applied on
control and as % of water control ( Table 33 ) show statisti top of tissues in duplicates . DMI and kojic acid were applied
cally -significant increase for all ATRA concentrations, at 2 .5 % and 2 % ( w :v ) respectively (dissolved in double
which provided technical validation of the experiment. All distilled water ). Tissue culture was pursued in the pigmen
test materials except retinoid ester were active , with ATRA tation -inducing medium EPI- 100 -NMM - 113 for 14 days ,
and Retinal being the best performers , followed by Near- 1 . with reapplication of test materials and changes of tissue
As determined by the Renilla readings , none of the com culture media every 2 - 3 days .
pounds were toxic at the tested concentrations . [0245] At the end of the experiment, tissue pigmentation
was quantified non - invasively with NS800 portable spectro
[0242 ] Conclusion : NEAR - 1 showed concentration photometer ( 3NH Technology Co ., Ltd ., China ). This instru
dependent impact on RXR -mediated gene expression and at ment is a reflectance spectrophotometer that measures
its highest tested concentration of 10 uM it demonstrated reflected light in the visible spectrum (range: 400 -700 nm )
statistically -significant modulatory effect (1.3 fold ). Addi recording colors in a three - dimensional space known as
tionally, retinal is 2 .4 times less effective in modulating RXR CIEL * a * b * color space . In this project, the L * value repre
pathway in comparison to retinoic acid at 5 uM . senting the lightness of the color was used for color assess
ment. For the purpose of this experiment, the range of the L *
TABLE 33 parameter spanned from 17 .8 (black background ) to 87. 8
Effect of test materials on the RXR -mediated (white background ).
gene expression showed as % water control. (0246 ) Tissue culture - conditioned media were assayed for
the presence of IL -8 by indirect ELISA (using Invitrogen
RXR activation IL - 8 Human CytoSet, cat. # CHC 1303 ).
Test Material % control) P value
102471 For melanin quantification , the MelanoDerms were
Water 100 1 .000 frozen , solubilized in SolvableTM (Perkin Elmer ) and mela
0 . 2 % DMSO 106 0 . 48 nin was extracted at 95° C . overnight. The colorimetric
5 uM ATRA 437 0 .000
signals proportional to the concentration of extracted mela
1 uM ATRA 340 0 .000
nin , as well as those proportional to the IL - 8 in the tissue
0 .2 uM ATRA 201 0 .000
10 uM Retinal 279 0 .000 conditioned medium in the ELISA test were quantified with
5uM Retinal 181 0 .000 Molecular Devices microplate spectrophotometerMAX190
1 uM Retinal 131 0 .001 at 490 nm and 405 nm .
10 uM NEAR - 1 127 0 .000
5 UM NEAR - 1 112 0 .000 10248 ] Results and Discussion : From the macroscopic
1 uM NEAR - 1 103
110
0 .000 documentation of all the MelanoDerm tissues at the end of
10 uM Retinoid Ester 0 .000 the experiment, differences of color are clearly visible
5 uM Retinoid Ester 99 0 .000 between the solvent controls and some test materials . Table
1 UM Retinoid Ester 124 0 .001
34 informs whether cytotoxicity may have played a role in
P values were calculated using two-tailed Student test. Bolded tests are experimental
conditions having statistically significant modulatory effect (220 % difference from water these differences. Table 34 also reports the non - invasive
control and p s 0 . 05 ) . MelanoDerm color measurement performed with portable
spectrophotometer.
TABLE 34
Cytotoxicity , spectrophotometric color measurements and
pigmentation ofMelanoDerm tissues exposed to different experimental
conditions for 2 weeks.
Color Melanin
measurement Melanin Content
(whitening Raw * L Content ( %
Test Material Cytotoxicity units ) values (ug/ml) control) p - value
Water No 42.8 84 100 1 .000
DMI:water No 45 . 5 N /A N /A N /A
US 2019 / 0099340 A1 Apr. 4 , 2019
28
TABLE 34- continued

Cytotoxicity, spectrophotometric colormeasurements and
pigmentation of MelanoDerm tissues exposed to different experimental
conditions for 2 weeks.
Color Melanin
measurement Melanin Content
(whitening Raw * L Content (%
Test Material Cytotoxicity units ) values (ug/ml) control) p -value
KA 2 % Yes 9.8 55 . 3 38 O
0 . 000
Retinaldehyde Yes 27 . 6 70
43838
. 0 . 002
1 .7 mM + NAD
1 .7 mM
Retinaldehyde No 26 . 7 69 . 5 N /A N /A N/ A
833 uM + NAD
833 UM
ATRA 832 UM +
NAD 835 uM
Yes 2828.. 22 071. 7
71 .0 8 0.000 0 .000
NEAR - 1
2 . 2 mM
Yes 27.4
27 . 4 70 .2 22
22 26
26 0.000
0 .000
NEAR - 1 No (possible
No ( possible 30.0 72.8 N /A N /A N /A
833 UM cytotoxicity )
Cytotoxicity of test materials was determined by microscopic observation of MelanoDerm tissues.
Non - invasive quantification of MelanoDerm pigmentation difference between test materials and solvent
control was performed with portable spectrophotometer.
Numbers represent the raw * L (brightness ) values ( higher the value - lighter the color ).
Pigmentation is expressed in ug/ml (melanin ) and as % water control.
N / A : not applicable .
[ 0249] At the end of the experiment, melanin extraction that niacinamide in this test was tested at 832 uM , is roughly
was initiated for selected tissues and completed two days 0 .01 % , which is 3 orders of magnitude ( about 500 times)
later. Data analysis revealed decreased tissue pigmentation lower than its effective concentration for skin brightening
by the tested compounds, at least in part due to cytotoxicity effect , used topically in cosmetic formulation . Therefore , we
( Table 34 ). consider its contribution to activity in this assay to be
[ 0250 ]. The quantification of interleukin 8 is reported in negligible.
FIG . 16 and Table 35 shows a strong upregulation of this What is claimed is :
proinflammatory cytokine by all tested retinoid combina 1. A topical skin composition comprising : retinaldehyde,
tions. one or more peptides, one or more skin conditioning agents ,
TABLE 35
one or more calcium containing agents , and, optionally , one
or more additional retinoids.
Actual numerical values corresponding 2 . The composition of claim 1, wherein the one or more
to the IL - 8 levels presented in FIG . 3 . additional retinoids is selected from the group consisting of
retinyl palmitate , alitretinoin ( 9 -cis -retinoic acid ), tretinoin
Test Material IL -8 (col. Units) p - value
(all - trans -retinoic acid ), isotretinoin ( 13 - cis-retinoic acid ),
Water 1 .000 etretinate , acitretin , adapalene, bexarotene, tazarotene ,
Solvent 1 .000 hydroxypinacolone retinoate (HPR ), retinoid ester, retino
(DMI/water ) ate , 2 -(nicotinamido )-ethyl retinoate (NEAR - 1), and deriva
KA 2 % 19 0 . 188
Retinaldehyde 195 0 .001 tives and combinations thereof.
1 . 7 mM + NAD
1 . 7 mM
3. The composition of claim 1, wherein the one or more
Retinaldehyde 206 0 .000
skin conditioning agents is selected from the group consist
833 UM + NAD ing of cyclopentasiloxane, dimethicone, polysilicone - 11 ,
833 UM ethylhexyl hydroxystearate, C12 - 15 alkyl benzoate, bis
ATRA 832 UM +
NAD 835 UM
219 0 .000 ethylhexyl hydroxydimethoxybenzylmalonate , ethoxy
NEAR - 1 2 . 2 mm 209 0 .001
diglycol, hyaluronic acid , alpha hydroxyl acids, glycolic
NEAR - 1 833 UM 208 0 .000 acid , lactic acid , ascorbic acid , polyhydroxy acids, glucono
Corresponding p values reflecting statistical significance ofvariance vs. water control col.
lactone , lactobionic acid , beta hydroxyl acid , peat extract,
units (colormetric units ). glycine , cetyl alcohol, stearyl alcohol, and derivatives and
combinations thereof.
[0251 ] Conclusion : In the retinoid category, NEAR - 1 at 4 . The composition of claim 1 , wherein the one or more
833 uM and [Retinaldehyde 833 uM + NAD 835 uM ] com peptides is selected from the group consisting of palmitoyl
bination appeared to provide the best whitening effect at hexapeptide - 14 , oligopeptide- 10 , myristoyl pentapeptide -8 ,
non -cytotoxic concentration . Additionally, retinoic acid + myristoyl tetrapeptide -8 , sericin , silk protein , collagen ,kera
niacinamide (both at 832 uM ) lightened melanoderma 78 % tin , amino acids, hexapeptide -21, palmitoyl oligopeptide,
more than untreated control. In contrast, retinal+ niacina palmitoyl tetrapeptide- 7 , tetrapeptide - 16 , polyacrylate - 13 ,
mide (both at 832 uM ) lightened the melanoderma 75 % polyisobutene, polysorbate - 20 , betaine, milk solids, rice
more versus untreated control, and was not cytotoxic . Note peptides, and derivatives and combinations thereof.
US 2019 /0099340 A1 Apr. 4 , 2019
5 . The composition of claim 1 , wherein the one or more 12 . The method of claim 7 , wherein the composition
calcium containing agents is selected from the group con comprises retinaldehyde, cyclopentasiloxane , dimethicone ,
sisting of hydroxyapatite , calcium lactate , calcium chloride, polysilicone-11, ethylhexyl hydroxystearate , C12 - 15 alkyl
calcium carbonate, calcium phosphate , calcium pyrophos benzoate , palmitoyl hexapeptide -14 , retinyl palmitate, bis
phate , calcium sulfate, dicalcium phosphate , dicalcium ethylhexyl hydroxydimethoxy benzylmalonate, hydroxy
phosphate dehydrate , tricalcium phosphate , calcium unde apatite, and ethoxydiglycol.
cylenate , and derivatives and combinations thereof. 13 . The method of claim 7, further comprising topically
6 . The composition of claim 1 , wherein the composition applying a second agent to the skin , wherein the second
comprises retinaldehyde , cyclopentasiloxane, dimethicone , agent is selected from the group consisting of a cleanser, a
polysilicone -11 , ethylhexyl hydroxystearate , C12 -15 alkyl toner, a moisturizer and any combination thereof.
benzoate , palmitoyl hexapeptide- 14 , retinyl palmitate , bis 14 . A method of treating skin comprising:
ethylhexyl hydroxydimethoxy benzylmalonate , hydroxy topically applying a composition to skin , wherein the
apatite, and ethoxydiglycol. composition comprises retinaldehyde , one or more
7 . A method of treating skin comprising : peptides , one or more skin conditioning agents , one or
(a ) rolling the skin with a micro -exfoliation tool, wherein more calcium containing agents , and , optionally, one or
the micro -exfoliating tool comprises a handle and a more additional retinoids,
head , the head comprising a roller, a mechanism of wherein treating the skin is an improvement in a charac
mounting the roller to the handle , and one or more teristic of the skin selected from the group consisting of
needles fixed to the roller ; and firmness , elasticity , fine lines and wrinkles, skin tex
(b ) topically applying a composition to skin , wherein the ture , dullness, dyschromia, skin tone, reduction or
composition comprises retinaldehyde, one or more elimination of acne, and any combination thereof.
peptides, one or more skin conditioning agents , one or 15 . The method of claim 14 , wherein the one or more
more calcium containing agents , and , optionally , one or additional retinoid is selected from the group consisting of
more additional retinoids, retinyl palmitate , alitretinoin (9 - cis - retinoic acid ), tretinoin
wherein treating the skin is an improvement in a charac ( all-trans -retinoic acid ), isotretinoin ( 13 -cis -retinoic acid ),
teristic ofthe skin selected from the group consisting of etretinate , acitretin , adapalene, bexarotene , tazarotene ,
firmness , elasticity, fine lines and wrinkles, skin tex hydroxypinacolone retinoate (HPR ), retinoid ester , retino
ture , dullness , dyschromia , skin tone, reduction or ate, 2 -( nicotinamido )- ethyl retinoate (NEAR - 1), and deriva
elimination of acne , and any combination thereof. tives and combinations thereof.
8 . The method of claim 7, wherein the one or more 16 . The method of claim 14 , wherein the one ormore skin
additional retinoid is selected from the group consisting of conditioning agents is selected from the group consisting of
retinyl palmitate, alitretinoin (9 -cis -retinoic acid ), tretinoin cyclopentasiloxane , dimethicone, polysilicone -11 , ethyl
( all-trans-retinoic acid ), isotretinoin (13 -cis -retinoic acid ), hexyl hydroxystearate , C12 - 15 alkyl benzoate , bis - ethyl
etretinate , acitretin , adapalene, bexarotene, tazarotene , hexyl hydroxydimethoxy benzylmalonate , ethoxydiglycol,
hydroxypinacolone retinoate (HPR ), retinoid ester, retino hyaluronic acid , alpha hydroxyl acids, glycolic acid , lactic
ate , 2 - nicotinamido ) -ethyl retinoate (NEAR - 1 ) , and deriva acid , ascorbic acid , polyhydroxy acids, gluconolactone , lac
tives and combinations thereof. tobionic acid , beta hydroxyl acid , peat extract, glycine , cetyl
9 . The method of claim 7 , wherein the one or more skin alcohol, stearyl alcohol, and derivatives and combinations
conditioning agents is selected from the group consisting of thereof.
cyclopentasiloxane , dimethicone, polysilicone -11 , ethyl
hexyl hydroxystearate , C12 -15 alkyl benzoate , bis -ethyl 17. The method of claim 14 , wherein the one or more
peptides is selected from the group consisting of palmitoyl
hexyl hydroxydimethoxy benzylmalonate, ethoxydiglycol, hexapeptide- 14 , oligopeptide- 10 ,myristoyl pentapeptide -8 ,
hyaluronic acid , alpha hydroxyl acids , glycolic acid , lactic myristoyl tetrapeptide- 8 , sericin , silk protein , collagen , kera
acid , ascorbic acid , polyhydroxy acids, gluconolactone , lac tin , amino acids, hexapeptide- 21, palmitoyl oligopeptide,
tobionic acid ,beta hydroxyl acid , peat extract, glycine , cetyl palmitoyl tetrapeptide -7 , tetrapeptide - 16 , polyacrylate - 13 ,
alcohol, stearyl alcohol, and derivatives and combinations polyisobutene , polysorbate - 20 , betaine , milk solids, rice
thereof. peptides, and derivatives and combinations thereof.
10 . The method of claim 7, wherein the one or more 18 . The method of claim 14 , wherein the one or more
peptides is selected from the group consisting of palmitoyl calcium containing agents is selected from the group con
hexapeptide- 14 , oligopeptide- 10 , myristoyl pentapeptide -8 , sisting of hydroxyapatite , calcium lactate , calcium chloride ,
myristoyl tetrapeptide- 8, sericin , silk protein , collagen , kera calcium carbonate, calcium phosphate , calcium pyrophos
tin , amino acids, hexapeptide- 21, palmitoyl oligopeptide, phate , calcium sulfate , dicalcium phosphate, dicalcium
palmitoyl tetrapeptide- 7 , tetrapeptide - 16 , polyacrylate- 13 , phosphate dehydrate, tricalcium phosphate , calcium unde
polyisobutene , polysorbate -20 , betaine, milk solids, rice cylenate , and derivatives and combinations thereof.
peptides, and derivatives and combinations thereof. 19 . The method of claim 14 , wherein the composition
11 . The method of claim 7 , wherein the one or more comprises retinaldehyde, cyclopentasiloxane, dimethicone,
calcium containing agents is selected from the group con polysilicone -11, ethylhexyl hydroxystearate , C12 - 15 alkyl
sisting of hydroxyapatite, calcium lactate , calcium chloride , benzoate , palmitoyl hexapeptide- 14 , retinyl palmitate, bis
calcium carbonate, calcium phosphate , calcium pyrophos ethylhexyl hydroxydimethoxy benzylmalonate , hydroxy
phate , calcium sulfate, dicalcium phosphate , dicalcium apatite, and ethoxydiglycol.
phosphate dehydrate , tricalcium phosphate, calcium unde
cylenate, and derivatives and combinations thereof.

US20190099340A1

Uploaded by

Copyright:

Available Formats

US20190099340A1

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

US20190099340A1

Uploaded by

Copyright:

Available Formats

US 20190099340A1

( 19) United States

$ aloos Ouipelo lejupo urcouevo % veow

.. . ... . .. . .. ... ? ? ? ? ? . ? . ? . ?. ?. ? . ????????????? . .. ?? ?? ? : ? . ?? ? . ? . .

' ' ' ' ' ' '

". . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .'. .'. . '. .'. ."

Colorimetric Arbitrary( 8-IL .

RETINALDEHYDE CONTAINING consisting of firmness, elasticity, fine lines and wrinkles,

TABLE 6 mula: Isododecane , Cyclopentasiloxane , Cyclohexasilox

Example 3: Clinical Study of Efficacy and TABLE 8

TABLE 18 tate , Atelocollagen , Zinc Phenosulfonate , Lecithin , PEG - 12

TABLE 21 -continued Example 7 : Silicone Gel with Retinal Formulation

after using the

TABLE 29 TABLE 31 -continued

Opti-MEM supplemented with 1 % MEM Non -essential Example 13 : Assessment of the

TABLE 34- continued

You might also like

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.