Expert Opinion on Therapeutic Patents

ISSN: 1354-3776 (Print) 1744-7674 (Online) Journal homepage: http://www.tandfonline.com/loi/ietp20

Bauhinia forficata in the treatment of diabetes

mellitus: a patent review

Bárbara Verônica Cardoso de Souza, Regilda Saraiva dos Reis Moreira

Araújo, Oskar Almeida Silva, Lucas Costa Faustino, Maria Fabrícia Beserra
Gonçalves, Mirian Lima Dos Santos, Grasielly Rocha Souza, Lindalva Moura
Rocha, Mônica Larissa Sousa Cardoso & Lívio César Cunha Nunes

To cite this article: Bárbara Verônica Cardoso de Souza, Regilda Saraiva dos Reis Moreira
Araújo, Oskar Almeida Silva, Lucas Costa Faustino, Maria Fabrícia Beserra Gonçalves, Mirian
Lima Dos Santos, Grasielly Rocha Souza, Lindalva Moura Rocha, Mônica Larissa Sousa Cardoso
& Lívio César Cunha Nunes (2018) Bauhinia forficata in the treatment of diabetes mellitus: a patent
review, Expert Opinion on Therapeutic Patents, 28:2, 129-138

To link to this article: https://doi.org/10.1080/13543776.2018.1409208

Accepted author version posted online: 23

Nov 2017.
Published online: 08 Dec 2017.

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EXPERT OPINION ON THERAPEUTIC PATENTS, 2018
VOL. 28, NO. 2, 129–138
https://doi.org/10.1080/13543776.2018.1409208

REVIEW

Bauhinia forficata in the treatment of diabetes mellitus: a patent review

Bárbara Verônica Cardoso de Souza a, Regilda Saraiva dos Reis Moreira Araújoa, Oskar Almeida Silvab,
Lucas Costa Faustinoc, Maria Fabrícia Beserra Gonçalvesa, Mirian Lima Dos Santosd, Grasielly Rocha Souza d
,
Lindalva Moura Rochae, Mônica Larissa Sousa Cardosoa and Lívio César Cunha Nunesd
a
Nutrition Department, Federal University of Piauí, Piauí, Brazil; bPostgraduate Program of Biotechnology, Federal University of Piauí, Piauí, Brazil;
c
Department of Chemistry, Federal University of Piauí, Piauí, Brazil; dDepartment of Pharmacy, Federal University of Piauí, Piauí, Brazil;
e
Postgraduate Program in Materials Science, Federal University of Piauí, Piauí, Brazil

ABSTRACT ARTICLE HISTORY

Introduction: Diabetes Mellitus has been considered an epidemic by the World Health Organization, Received 12 September 2017
with a high risk of morbidity and mortality. The treatment of this pathology consists in glycemic control, Accepted 21 November 2017
which can be done by oral hypoglycemic agents, insulin therapy, dietary guidance, regular physical KEYWORDS
activity, and psychosocial support. In addition, other adjuvant treatments are employed, such as Bauhinia forficata; diabetes
phytotherapic, and one of the most used plants is Bauhinia forficata. mellitus; phytotherapy;
Areas covered: In the current review, patents using Bauhinia forficata for the Diabetes Mellitus Flavonoids; kaempferol;
treatment have been analyzed. There were 03 patents in WIPO, 01 in Espacenet, 01 in USPTO, and 02 insulin resistance
in INPI.
Expert opinion: Patents on the adjuvant treatment of Diabetes Mellitus by Bauhinia forficata are
discussed. Although there are some phytotherapy products containing this medicinal plant which has
hypoglycemic effect here is still a need for the development of more products based on natural
resources, for the treatment of this pathology, without side effects and with other benefits, to assist
in the glycemia control in diabetic patients, and to improve their quality of life.

1. Introduction The treatment for this pathology consists of acquiring

knowledge about the disease, insulin therapy, ability to self-
Diabetes mellitus (DM) is a metabolic disease characterized by
apply insulin and glycemic self-control, oral hypoglycemic
hyperglycemia, which can be of two types in the clinical
agents, food orientation, regular physical activity, and psycho-
practice: type 1 (DM1) (autoimmune), in which there is a
social support [6]. In addition, other adjuvant treatments are
partial or total destruction of the β cells of the islets of
employed, such as phytotherapy. Several medicinal plants
Langerhans in the pancreas, resulting in a progressive inability
have been used for the DM treatment, especially type 2,
to produce insulin; and type 2 (DM2) (insufficiency of secretion
with a positive impact on glucose and lipid metabolism,
and/or insulin action). The first is diagnosed in younger popu-
improving the general condition of the patients, not only by
lation and represents only a small percentage of the total
the hypoglycemic effect, but also by the antioxidant action of
number of patients diagnosed with diabetes. The type 2 is
these plants. Among these plants, stands out the Bauhinia
the most common form of diabetes, in which the main risk
forficata, described by Link in 1821 and inserted in the family
factors for its development, besides a genetic predisposition,
Leguminosae, later called Fabaceae, and popularly known as
are dietary quality and lifestyle. There is also a form of auto-
‘cow’s foot’ or vegetable insulin. This genus comprises about
immune diabetes diagnosed in the adult, called latent auto-
300 species found especially in the tropical regions of the
immune diabetes in adults (LADA), which suggests the
planet [7].
possibility of a pathophysiological continuity between the
The first clinical trial with this species was registered in
two main types of DM [1–4].
1929, and from this date, aqueous extracts made of its leaves
The DM2 prevalence has increased globally due to popula-
have been widely used in the diabetes treatment [8]. Several
tion aging, urbanization, obesity, and sedentary lifestyle. It has
studies show that the leaves of this plant are considered
been considered an epidemic by the World Health
antidiabetic, hypoglycemic, antioxidant, hepatoprotective,
Organization, with a high risk of morbidity and mortality.
diuretic, hypocholesterolemic, and also have beneficial effect
Decompensated DM2 can cause various changes in carbohy-
in folk medicine against cystitis and intestinal parasitosis [9].
drate, protein and lipid metabolism, peripheral nerve damage,
These diverse biological properties of Bauhinia forficata
kidney damage, causing severe complications, including blood
have been attributed to their constituents, which include
circulation problems, retinal eye injury, consequently blind-
lactones, flavonoids, terpenoids, glycolipids, steroids, and
ness, nerve damage, among others [5].

CONTACT Bárbara Verônica Cardoso de Souza barbara.vscardoso@ufpi.edu.br Nutrition Department, Federal University of Piauí, Piauí, Brazil
Supplemental date for this article can be accessed here.
© 2017 Informa UK Limited, trading as Taylor & Francis Group
130 B. V. C. D. SOUZA ET AL.

complications. Thus, this patent review supports a better

Article highlights prospection for future studies on the use of B. forficata in
● The flavonoid kaempferol from the Bauhinia forficata leaves has a
the DM2 treatment, increasing the prophylactic and thera-
hypoglycemic and antioxidant effects. peutic possibilities for the patients with this pathology.
● A composition with B. forficata extracts and other medicinal plants
showed a hypoglycemic effect in humans.
● Infusion with Bauhinia forficata leaves obtained a hypoglycemic 2. Methods
effect in diabetic patients.
The patents were searched in the World Intellectual Property
This box summarizes key points contained in the article.
Organization (WIPO), European Patent Office (Espacenet),
United States Patent and Trademark Office (USPTO), and
National Institute of Intellectual Property (Instituto Nacional de
Propriedade Intelectual – INPI) databases. The patents selec-
tannins. The main bioactive compounds of B. forficata are tion was based on the following inclusion criteria: published
flavonoids, which are an important class of polyphenols, patents containing Bauhinia forficata and DM as keywords in
present in relative abundance among secondary plant the title, abstract, or full text.
metabolites, being kaempferol 3,7-di-O-α-L-rhamnoside, A total of 29 patents were found for preliminary evaluation
also known as kaempferitrin being the main chemical and of the databases (Figure 1). Of these patents, 10 that were
pharmacological marker responsible for hypoglycemic duplicated and 12 patents that were outside of the review
activity [10–12]. focus were excluded, as patents reporting other pathologies
Although the synthetic drugs available on the market treated by Bauhinia forficata such as cancer, osteoporosis,
have a significant hypoglycemic effect, they also cause sev- weight reduction, anxiety, influenza, and studies with other
eral side effects, and are not effective in preventing the Bauhinia species.
occurrence of complications. Therefore, research on phy- It was selected for this review 7 patents on Bauhinia for-
totherapeutic drugs is important because they have effec- ficata use in the diabetes mellitus treatment. These patents
tive effects on glycemia, besides they do not have were deposited in three countries: Brazil, United States, and
undesirable side effects of synthetic drugs, preventing Japan (Figure 1).

Figure 1. Diagram of research and screening of the analyzed patents.

 EXPERT OPINION ON THERAPEUTIC PATENTS 131

3. Patent analysis Referring to the antioxidant activity of flavonoids, this

depends on the arrangement of their functional groups, and
3.1. Flavonoids in the diabetes treatment
the configuration, substitution, and total number of hydroxyl
The invention (US20130231492) was developed by Hongquan groups influence several mechanisms of this activity [21,22].
et al. and relates to a class of new compounds derived from Such mechanisms of this antioxidant action are related to the
flavonoids, as well as a method of preparation and its applica- inhibition of enzymes involved in the production of free radi-
tion as antidiabetic drug. Flavonoids are polyphenolic com- cals (microsomal monooxygenase, glutathione S-transferase,
pounds, widely found in fruits, leaves, teas, and wines. They mitochondrial succinoxidase, NADH oxidase) [23]. This is due
are constituted by three rings, in which carbons can undergo to the redox potential of flavonoids that are capable of redu-
chemical variations such as hydroxylation, hydrogenation, cing highly oxidizing free radicals such as superoxide, peroxyl,
methylation, and sulfonation, forming more than four thou- alkoxyl, and hydroxyl radicals by hydrogen atom donation.
sand flavonoid compounds which are grouped in classes. They also have the action of chelating metal ions (iron, copper,
There are six major classes of flavonoids, including anthocya- etc.), and inhibiting the synthesis of radicals [24,25], for exam-
nins (cyanidin, pelargonidin, delphinidin, malvidin), flavonols ple, quercetin is known for its chelating properties and stabi-
(quercetin, rutin, kampferol and myricetin), flavanols (epicate- lizing iron; catechins inhibit lipid peroxidation; epicatechin and
chins, luteophorol, proceanidines and theaflavins), flavanones rutin are strong radical scavengers and inhibitors of lipid
(hesperidin and naringerin), flavones (apigenin and luteolin), peroxidation in vitro [26].
and isoflavones (daidzein, genistein). Each of these classes of Flavonoids specifically act on the enzymatic functions of
flavonoids is distinguished by the number and arrangement of the inflammatory process, inhibiting the release of histamines,
the hydroxyl groups and their extent of alkylation and glyco- through the inhibition of phosphodiesterases, of the protein
sylation, as can be seen in flavonol kaempferol 3,7-di-O-α-L- kinases (PK), binding competitively with the ATP enzymes
rhamnoside (kaempferitrin; Figure 2) [13–17]. associated with signal transduction and to the activation of
These polyphenols act in the human body as antioxidants, immunological mechanisms. The anti-inflammatory activity of
antiallergics, anti-inflammatory, anti-viral and antimicrobial, these bioactive compounds also occurs by modulating cells
antiproliferative, anti-mutagenic, anti-carcinogenic, eliminat- involved with inflammation (inhibit proliferation of mast cells,
ing free radicals, regulating the cell cycle, regulating the cell T cells, B cells, NK cells, and neutrophils) and the inhibition of
cycle, modulating some important cell signaling pathways, the synthesis of proinflammatory cytokines TNF-α (IL-1),
such as nuclear factor Kappa-B (NF-kB), AP-1 transcription released by activated macrophages and several other cell
factors, and the nuclear acetylation/deacetylation of histone, types, being responsible for the induction of apoptosis and
extracellular signal-regulated protein kinase (ERK), inositol tri- inhibition of the NF-κB pathway [27–33].
phosphate (IP3)/protein kinase B (Akt), mitogen-activated pro- Another mechanism of action of flavonoids in the inflam-
tein kinases (MAPK), and nuclear redox factor (Nrf2) [18–20]. matory process is through the inhibition of the activity of the

Figure 2. a) Chemical structure of Flavonoid b) Chemical structure of Kaempferol c) Chemical structure of Kaempferol 3,7-di-O-a-L-rhamnoside.
132 B. V. C. D. SOUZA ET AL.

enzymes of the arachidonic acid pathway, phospholipase A2 of action by which metformin exerts its pharmacological
(PLA2), cyclooxygenase (COX), and lipoxygenase (LOX), redu- action. This cellular enzyme is stimulated by physical exercise,
cing the production of eicosanoids, and modulate expression so the prescription of diet and physical activity for individuals
of nitric oxide synthase (iNOS), which results in the inhibition with DM2 is closely related to the activation of AMPK, which
of nitric oxide production [34–39]. The chemical structure of seems to be responsible for many beneficial effects in the
these compounds is responsible for their anti-inflammatory treatment and prevention of the disease [13,45–47].
activity, such as C-ring unsaturation (2–3 positions), the num- Mokashi, Khanna and Pandita [48] also evaluated the flavo-
ber and position of hydroxyl groups, C-4 carbonyl (Ring B), and noids antidiabetic activity in insulin resistant HepG2 cells, and
glycosylation of the molecule. Some subclasses of flavonoids, obtained similar results to those of US20130231492 invention.
even without this structure, for example, aglone kaempferol, The researchers used this HepG2 cell line model to mimic the
are also notable for their activity on enzymes in the inflamma- in vivo condition of DM2. It was observed that flavonoid-
tion cascade [40]. treated cells increased GLUT4 translocation to the cell mem-
Chronic inflammation is directly related to many diseases, brane, with consequent increase in glucose uptake, in addition
including cancer, allergies, arthritis, cardiovascular diseases, to a decrease in insulin resistance, confirming that flavonoids
and diabetes, and flavonoids due to their potent anti-inflam- represent a promising treatment for diabetes mellitus type 2.
matory actions and antioxidants, as previously explained, have
been targets of new therapeutic strategies for these patholo-
gies [41]. 3.2. Bauhinia forficata associated with other bioactive
Hyperglycemia in DM2 is caused by altered digestion and compounds in the diabetes treatment
absorption of dietary carbohydrate, glycogen storage deple- Bioactive compounds from medicinal plants have proven ben-
tion, increased gluconeogenesis, pancreatic β-cell dysfunction, eficial effects on diabetes, improving glycemic control, lipid
peripheral tissue insulin resistance, and failures in insulin sig- profile, and antioxidant status. Such compounds may be alka-
naling pathways. Flavonoids act as hypoglycemic agents by loids, carbohydrates, glycosides, flavonoids, steroids, terpe-
reducing intestinal absorption of dietary carbohydrates, mod- noids, peptides and amino acids, lipids, phenolics,
ulating the enzymes involved in glucose metabolism (inhibit- glycopeptides, and iridoids [49,50].
ing α-glycosidase), improving β-cell function, and insulin Phytochemicals reduce blood glucose and prevent the
secretion and action, and by their properties as antioxidant absorption of glucose from the gastrointestinal tract. This
and anti-inflammatory agents [42,43]. hypoglycemic effect is due to increased insulin secretion
Yeon, Bae, Kim and Lee [44] performed a study with 4186 through pancreatic β-cell stimulation; glucagon hormone
participants, divided into two groups according to fasting resistance that increases blood glucose levels; increased num-
glycemia: normal fasting blood glucose (up to 100 mg/dl) ber and sensitivity of insulin receptors; decreased glycogen
and fasting blood glucose ≥100 mg/dl who investigated the loss; increased consumption of glucose in tissues and organs;
association between flavonoid intake and risk of type 2 dia- insulinomimetic paper; elimination of free radicals; stimulation
betes mellitus (DM2) and found that the intake of these bioac- to increase blood microcirculation, inhibition of α-glycosides
tive compounds was lower in the hyperglycemic group and and other actions, such as reduction in intestinal transit
that insulin resistance had an inverse relationship to the intake [51,52]. Hosseini, Shafiee-Nick and Ghorbani [53] reported
of flavones and flavonols among individuals confirming the that the antidiabetic activity of some phytochemicals is
hypoglycemic effect. mediated by the inhibition of beta cell degeneration.
In the patent US20130231492, in vivo tests were conducted There are several medicinal plants with proven hypoglyce-
and the dosages were between 2ug/ml and 5ug/ml, in which mic and antidiabetic effects, among them the Moringa oleifera,
was found that flavone derivatives can significantly increase Abelmoschus esculentus Lycium barbarum, Rourea cuspidata,
the glucose consumption of hepatocellular carcinoma cells Gentiana olivieri, Bauhinia forficata, Eugenia jambolana,
(HepG2) insulin resistant, increase the absorption and utiliza- Lactuca indica, Mucuna pruriens, Tocophera cordifolia,
tion of glucose, and promote the translocation of the glucose Momordica charantia, Aporosa lindleyana, Myrtus communis,
transporter in the skeletal muscle cells (GLUT4) at different and Terminalia pallida [54].
levels. This last effect is one of the main mechanisms for the Fombang and Saa [55] have shown that Moringa oleifera
diabetes treatment, providing the application of these bioac- tea has antihyperglycemic and antioxidant activity in rat and
tive compounds for antidiabetic drug production [13,45]. human models, being attributed to its content of polyphenols,
Some of the compounds tested had comparable and/or particularly phenolic acids, flavonoids, and tannins, which
superior antidiabetic activity than the metformin, in addition inhibit α-amylase, α-glucosidase, and intestinal glucose
to a greater effect than insulin on GLUT4 translocation in uptake; improve glucose uptake by peripheral tissues, sup-
skeletal muscle cells. These researchers also elucidated one press gluconeogenesis, and stimulate insulin secretion
of the molecular mechanisms of the antidiabetic effect of [56–61].
flavonoid derivatives, which occurs by the activation of AMP- A recent study confirmed the in vivo hypoglycemic activity
activated protein kinase (AMPK), one [20–22], an enzyme that of okra (Abelmoschus esculentus L. Moench) in vivo, from which
acts on cellular metabolism, maintaining energy homeostasis the rhamnogalacturonan polysaccharide was extracted and its
and inducing a cascade of intracellular events in response to a hypoglycemic effect was tested in streptozotocin-induced dia-
change in the cellular energy load, being the same mechanism betic rats, which showed a decrease in blood glucose level
 EXPERT OPINION ON THERAPEUTIC PATENTS 133

and glucose tolerance [62]. Besides this activity, this bioactive Syzygium jambolanum (Jambolão) seeds, and prepared for
polysaccharide improves diabetic nephropathy and increases oral administration in the form of microgranules, pellets,
the proliferation of splenocytes and the secretion of cytokines, tablet, or powder.
acting as an immunomodulator [63,64]. The extracts of this invention were obtained by mixing, by
Lycium barbarum, a fruit that also has in its composition mass, 19% of Bauhinia leaves, 52.5% of alcohol, and 28.5% of
bioactive polysaccharides, mainly mannose, rhamnose, glu- water, and between 9% and 19% of Jambolão seeds, 57–64%
cose, galactose, and xylose, inhibited the absorption of glu- of alcohol, and 24–27% of water. The amount of B. forficata
cose in vitro and may be a potent antidiabetic agent [65]. extract and S. jambolanum contained in the pellet was 1–90%.
Another plant with activity with this activity is Rourea cuspi- The inventors of this BR1020150157690 patent tested these
data, whose continuous administration of 200 mg/kg of its extracts in streptozotocin-induced diabetic rats of the Wistar
hydroalcoholic extract, in vivo, significantly reduced the blood line, for 42 days. These animals had their serum glucose levels
glucose concentration of diabetic rats, with a similar effect to reduced to values similar to those observed in the animals of
glibenclamide, which acts stimulating the secretion of insulin the group that received metformin, and it was verified the
from β cells of the islets of Langerhans, and the hyperin, antidiabetogenic activity of the pellets with these vegetal
present in this plant, may be the hypoglycemic agent, since extracts.
it has the capacity to increase glycolysis, due to the increase in The invention (US20140186321) was developed by Thomas
liver hexokinase activity and decrease activities of gluconeo- Christian Lines and relates to a method to treat metabolic
genic enzymes [66–68]. syndrome or diabetes by administering an effective amount
Herwig, Corinna, Valerie, Doeclecio and Didier (JP2012102144; of a composition containing quercetin, vitamin B3, vitamins C
JP2005504753; US20040170714; US2006018859; WO2003011311) and B. fortificata extract. This composition may be a dietary
performed tests with several extracts of Bauhinia spp, which supplement or a pharmaceutical formulation, of which may be
showed hypoglycemic activity, and is an alternative for the dia- presented in solid form (powder or tablet) or in liquid form
betes treatment, acting as an oral hypoglycemic agent. This inven- (beverage or syrup) [76].
tion patented the extraction production methods, which According to this invention, the combination of quercetin
consisted in the use of an ethanol and water mixture as solvent with B. fortificata potentiates the beneficial effects in patients
extractor of the compounds in the B. fortificata young leaves, with DM2, because there is an increase in blood flow, con-
containing 30–70% of water. Besides the method of extraction, a siderably reducing the risk of thrombotic events, lowering
medicine and a food supplement based on Bauhinia extracts were blood pressure, and synergistically increasing sensitivity to
made [69]. insulin. This composition may also be associated with a hypo-
The extract can be made from any aerial parts of the glycemic drug or with the use of insulin to improve its efficacy,
Bauhinia species. However, the best results were found with allowing the individual to be treated with lower doses of the
the extracts obtained from young leaves. Therefore, they were drug and of the synthetic hormone. Therefore, there is a side
chosen for the extracts production of this patent cited above, effects reduction (weight gain, nausea, hypoglycemia, diar-
and the extraction should preferably occur from the B. fortifi- rhea, flatulence, inappetence, liver damage, fluid retention,
cata leaves. and stomach pain). The developed formulation may be admi-
The hypoglycemic activity found in this invention was simi- nistered concomitantly with the medication or at different
lar to the effect obtained by drugs, such as metformin. This times before meals, at a dose of 100mg to 2g of quercetin
effect is due to the combined action of different bioactive (preferably 250mg to 1g), and 50mg to 6g of B. fortificata
compounds as flavones or flavonoids (isoquercetina, kaemp- extract (preferably 125 mg to 0.5 g).
ferol, quercetin, rutin). Supplementation was done at a dosage The US20060189512 patent [77] describes the develop-
of 150 mg extract/kg of body weight, twice a day, resulting in ment of a dietary supplement, based on florizine extract, B.
improved glucose tolerance and increased excretion thereof. forficate, and other plants which have hypoglycemic effects. In
Another beneficial effect observed was the antioxidant action addition to the glycemia reduction, glucose excretion and
of these extracts. In vitro and in vivo studies have shown that reduction in postprandial insulin levels, it was also found
oxidative stress decreases insulin secretion from pancreatic β that this supplement facilitated weight loss and increased
cells and interferes in the insulin signaling pathway, causing longevity, decreasing the onset or incidence of aging-related
insulin resistance and type 2 diabetes [70–74]. diseases.
In the medicine formulation of the invention JP201210214, The beneficial effects of this invention were enhanced by
in addition to Bauhinia extract (0.01–99%), it was added vita- the synergy of florizine extract administered with other ele-
mins C and E, alpha-lipoic acid, flavonoids, glutathione, caro- ments. Such elements are quercetin, floretin, epicatechin, cate-
tenoids, coenzyme Q10, zinc, and selenium bound to the chins, chlorogenic acid, and other flavonoids. It was also found
proteins, to optimize the antioxidant activity of the drug. The that the association of this supplement with drugs for DM
food supplement composition included vitamins, minerals, treatment also potentiates its hypoglycemic effect. The
probiotics, prebiotics, fatty acids, flavonoids, polysaccharides, dosage of this dietary supplement should be 3 to 30 g per
lipoic acid, and Bauhinia extract (0.01–99%). day, administered in three separate doses, between 1 and
Moffa and Calefe [75] have patented processes to obtain 10 g, about 30 to 60 min before meals [77].
concentrated herbal extracts for the product production for Another invention that has also used the B. forficata extract
type 2 diabetes treatment, obtained using it alone or in com- associated with other compounds was developed by Fogel
bination with the concentrated B. forficata extracts and (US20100202980; US20150190446; WO2009001362; IL202980;
134 B. V. C. D. SOUZA ET AL.

EP 2,170,360) [78]. This patent reports a plant-based composi- A study conducted with pre-diabetic and diabetic
tion of Urtica dioica, U. urens, U. pilulifera, Artemisia dracunculus, patients, who used a 0.15% dose of B. forficata infusion,
A. alba, A. herba, A. roxburghiana, A. judaica, Morus alba, M. three times a day, after meals for 3 months, showed that
bombycis, M. indica, M. insignis, M. nigra, M. austral, B. forficata, there was a significant reduction in the glycemia of these
Cinnamomum zeylanicum, C. saigonicum, C. aromaticum, C. patients, suggesting that tea of this species could be use-
laurus, Canella winterana, Taraxacum officinale, and Rosa canina. ful in the prevention or complementary treatment of DM2
The referred composition can be a dietary supplement and [86]. Another study with diabetic patients, who also used
a pharmaceutical formulation, both with acceptable excipients the infusion of B. forticata, obtained a decrease in their
(maltodextrin, calcium phosphate, and aerosil), the presenta- glycemic profile during the intervention period (75 days)
tions may be in the form of tea, tincture, tablet, capsule, pill, [87]. These results are similar to those verified by Zaccaron
bar, chewing gum, lotion, powder, or granules. The health [88], that evaluated blood pressure and fasting blood glu-
claims of this invention are for the DM2 treatment and/or cose levels of all patients with DM2 from a Basic Health
prevention and dyslipidemias and/or associated conditions, Unit and found that the patients who took tea from the
and the therapeutic dose is from 1000mg to 6 g per day [78]. leaves of B. forficata, during 180 days, showed a decrease
in glucose values when compared to the group of patients
who did not use the infusion, which indicates the effi-
3.3. Bauhinia forficata in the diabetes treatment
ciency of this herbal medicine in the treatment of this
Bauhinia forficata has several chemical constituents, especially pathology.
flavonoids, especially canpherolic and quercetin glycosides.
Among these, kaempferol 3,7-di-O-α-L-rhamnoside or kaemp-
4. Conclusion
feritrin is considered as the chemical marker for those of
leaves of B. forficata subsp forficata, since it is present in this, It was concluded that these patents highlight the different
but absent in B. forficata subsp. Pruinosa (Vogel) Fortunato & products developed based on Bauhinia forficata and other
Wunderlin [79–81]. bioactive compounds used in the prophylaxis and treatment
Due to the presence of these bioactive compounds, of diabetes mellitus, especially type 2. The phytotherapic pro-
Bauhinia forficata exerts several activities beneficial to the ducts studied have several advantages when compared to the
body as antioxidant, antidiabetic and hypoglycemic, anti- synthetic hypoglycemic drugs, because they control glycemia
inflammatory, antimicrobial, antitumor, anticoagulant, with without causing adverse effects. Besides, they have other
application in the treatment of diseases such as cancer, meta- biological functional properties, such as antioxidant, hypoten-
bolic syndrome, obesity, osteoporosis, Alzheimer’s, and dia- sive, hypocholesterolemic, anticoagulant, and anti-inflamma-
betes [82]. tory activities. The researches demonstrate the growing
Rolim et al (BR1020130241504) have patented an invention interest of the pharmaceutical industry and academies in the
which describes an effervescent pharmaceutical composition development of hypoglycemic agents from natural products
for DM treatment based on the dry extract of Bauhinia for- for the diabetes mellitus treatment, to improve the quality of
ficata. This formulation consisted of dry ethanolic extract of life of the patients affected by this pathology.
Bauhinia forficata (15–70%), effervescent base (36–76%), citric
acid (6–12%), tartaric acid (10–24%), sodium bicarbonate (20–
5. Expert opinion
40%), drying adjuvant (colloidal silicon dioxide) (10–30%),
sweetener (sucralose) (8–14%), a binder (polyvinylpyrrolidone), DM2 is a metabolic disorder characterized by chronic hyper-
and excipient (coloring, flavoring, diluent, disintegrating, lubri- glycemia, being a cardiovascular risk factor, with high morbid-
cating, wetting, absorbent). The effervescent pharmaceutical ity and mortality. Elevated postprandial glucose levels can
composition can be presented as a powder, granule, or tablet, trigger the production of reactive oxygen species (ROS),
being an alternative for diabetic patients [83]. decrease insulin secretion and interfere with its signaling path-
Da Cunha et al. [84] carried out a study in diabetic-induced way, as well as cause micro and macrovascular complications
rats by streptozotocin in which the hypoglycemic effects of [89–93].
different B. forficata dry extracts were verified, using a single The glycemic metabolism control in DM is necessary to
dose of 200 mg/kg of body weight. After the administration of avoid the appearance of those complications. The body tries
B. forficata extracts, an average reduction of 47.29% of the to compensate the glucose excess and the constant insulin
plasma glucose of these animals was observed. resistance by increasing insulin production and secretion.
Salgueiro et al. [85] investigated the effects of Bauhinia However, this compensatory mechanism cannot act continu-
forficata link subsp. pruinose tea, and its effect against oxida- ously, progressing to a systemic inflammation, and conse-
tive stress and liver damage in diabetic rats. The results quently reduction in insulin secretion by β cells and their
showed that B. forficata tea reduced oxidative stress, but did apoptosis, leading to the disease progression [94,95].
not change glycemia, unlike previous studies. Thus, the Flavonoids have anti-inflammatory, antioxidant, and che-
researchers inferred that the absence of the hypoglycemic mopreventive properties. In vitro and in vivo studies have
action of B. forficata tea may be due to the inactivation of found that these compounds can eliminate free radicals and
the compound kaempferitrin, the main substance responsible chelators inducing oxidation, reducing the risk of cardiovascu-
for the hypoglycemic action, that may have been lost during lar diseases, lowering glycemia, and improving secretion and
the infusion preparation. sensitivity of insulin [96–99].
Table 1. Patents about Bauhinia forficata in the Diabetes Mellitus treatment.
Country
of Mechanism of Prophylaxis or Route of
Patents Inventors/Company (Parents) protection Year CIP Formulation action treatment administration Presentation form Referência
US20130231492 Duan Hongquan et al. US 2013 C07D Class of new compounds Diabetes treatment Treatment Oral Solid [13]
DUAN HONGQUAN A61K derived from flavonoids, and insulin
QIN NAN method of preparation and resistance.
NIU WENYAN their application as
JIN MEINA antidiabetic drug.
SHI LIHUAN
CHEN YING
(USA)
JP2012/102144 Buchholz Herwig et al. JP 2012 A61K Extract of ethanol and water, Reduction of plasma Treatment Oral Hydroalcoholic [24]
MERCK PATENT GMBH A61P containing 30 to 70% by glucose extract.
(Japão) A23L volume of water as solvent. concentration.
BR1020150157690 Mario Moffa et al. BR 2015 A61K Pharmaceutical form with Type 2 Diabetes Treatment Oral Pellets, tablet or [30]
MARIO MOFFA, LUPERCIO CALEFE A61P Bauhinia forficata and treatment powder.
(Brazil) Syzygium jambolanum
extracts
US 2014/0186321 Thomas Christian Lines US 2014 A61K Composition containing Glucose and blood Treatment Oral e Powder or tablet; [31]
Thomas Christian Lines quercetin, vitamin B3, pressure parenteral liquid, capsule,
(USA) vitamin C and B. fortificata reduction, and chewing gum or
extract. insulin resistance. gel).
US20060189512 Ehrenkranz Joel R. L. US 2006 A61K Compositions containing Reduction of Treatment Oral Dietary [32]
EHRENKRANZ JOEL R. L. A23L botanical extracts rich in glucose levels in supplement or
(USA) A23V florizin, Bauhinia forficata blood and urine, nutraceuticals in
and other plants with weight control, the form of
hypoglycemic effect. premature aging. tablet, capsule
or powder.
US20150190446 Fogel Dov US 2015 A61K Composition based on the Treatment and/or Treatment and Oral Tea, tincture, [33]
ASCARIT LTD. A61P plants prevention of prophylaxis tablet, capsule,
(USA) Urtica, diabetes and pill, bar,
Artemisia, Morus, Bauhinia related disorders lozenge,
forficata and other plants and dyslipidemia. chewing gum,
with hypoglycemic effect. lotion, powder
or granules.
BR1O2013024150 Larissa Araújo Rolim et al. BR 2013 A61K Effervescent pharmaceutical Diabetes treatment Treatment Oral Powder, granulate [83]
UNIVERSIDADE FEDERAL DE A61P composition with Bauhinia or tablet.
PERNAMBUCO forficata ethanolic extract.
(Brazil)
Abbreviations: WO: International Patent; US: United States; JP: Japan; BR: Brazil.
EXPERT OPINION ON THERAPEUTIC PATENTS
135
136 B. V. C. D. SOUZA ET AL.

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