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

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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.
Article highlights
● The flavonoid kaempferol from the Bauhinia forficata leaves has a
hypoglycemic and antioxidant effects.
● A composition with B. forficata extracts and other medicinal plants
showed a hypoglycemic effect in humans.
● Infusion with Bauhinia forficata leaves obtained a hypoglycemic
effect in diabetic patients.
This box summarizes key points contained in the article.
tannins. The main bioactive compounds of B. forficata are
flavonoids, which are an important class of polyphenols,
present in relative abundance among secondary plant
metabolites, being kaempferol 3,7-di-O-α-L-rhamnoside,
also known as kaempferitrin being the main chemical and
pharmacological marker responsible for hypoglycemic
activity [10–12].
Although the synthetic drugs available on the market
have a significant hypoglycemic effect, they also cause sev-
eral side effects, and are not effective in preventing the
occurrence of complications. Therefore, research on phy-
totherapeutic drugs is important because they have effec-
tive effects on glycemia, besides they do not have
undesirable side effects of synthetic drugs, preventing
Figure 1. Diagram of research and screening of the analyzed patents.
complications. Thus, this patent review supports a better
prospection for future studies on the use of B. forficata in
the DM2 treatment, increasing the prophylactic and thera-
peutic possibilities for the patients with this pathology.
2. Methods
The patents were searched in the World Intellectual Property
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-
tion was based on the following inclusion criteria: published
patents containing Bauhinia forficata and DM as keywords in
the title, abstract, or full text.
A total of 29 patents were found for preliminary evaluation
of the databases (Figure 1). Of these patents, 10 that were
duplicated and 12 patents that were outside of the review
focus were excluded, as patents reporting other pathologies
treated by Bauhinia forficata such as cancer, osteoporosis,
weight reduction, anxiety, influenza, and studies with other
Bauhinia species.
It was selected for this review 7 patents on Bauhinia for-
ficata use in the diabetes mellitus treatment. These patents
were deposited in three countries: Brazil, United States, and
Japan (Figure 1).

3. Patent analysis
3.1. Flavonoids in the diabetes treatment
The invention (US20130231492) was developed by Hongquan
et al. and relates to a class of new compounds derived from
flavonoids, as well as a method of preparation and its applica-
tion as antidiabetic drug. Flavonoids are polyphenolic com-
pounds, widely found in fruits, leaves, teas, and wines. They
are constituted by three rings, in which carbons can undergo
chemical variations such as hydroxylation, hydrogenation,
methylation, and sulfonation, forming more than four thou-
sand flavonoid compounds which are grouped in classes.
There are six major classes of flavonoids, including anthocya-
nins (cyanidin, pelargonidin, delphinidin, malvidin), flavonols
(quercetin, rutin, kampferol and myricetin), flavanols (epicate-
chins, luteophorol, proceanidines and theaflavins), flavanones
(hesperidin and naringerin), flavones (apigenin and luteolin),
and isoflavones (daidzein, genistein). Each of these classes of
flavonoids is distinguished by the number and arrangement of
the hydroxyl groups and their extent of alkylation and glyco-
sylation, as can be seen in flavonol kaempferol 3,7-di-O-α-L-
rhamnoside (kaempferitrin; Figure 2) [13–17].
These polyphenols act in the human body as antioxidants,
antiallergics, anti-inflammatory, anti-viral and antimicrobial,
antiproliferative, anti-mutagenic, anti-carcinogenic, eliminat-
ing free radicals, regulating the cell cycle, regulating the cell
cycle, modulating some important cell signaling pathways,
such as nuclear factor Kappa-B (NF-kB), AP-1 transcription
factors, and the nuclear acetylation/deacetylation of histone,
extracellular signal-regulated protein kinase (ERK), inositol tri-
phosphate (IP3)/protein kinase B (Akt), mitogen-activated pro-
tein kinases (MAPK), and nuclear redox factor (Nrf2) [18–20].
Figure 2. a) Chemical structure of Flavonoid b) Chemical structure of Kaempferol c) Chemical structure of Kaempferol 3,7-di-O-a-L-rhamnoside.
EXPERT OPINION ON THERAPEUTIC PATENTS 131
Referring to the antioxidant activity of flavonoids, this
depends on the arrangement of their functional groups, and
the configuration, substitution, and total number of hydroxyl
groups influence several mechanisms of this activity [21,22].
Such mechanisms of this antioxidant action are related to the
inhibition of enzymes involved in the production of free radi-
cals (microsomal monooxygenase, glutathione S-transferase,
mitochondrial succinoxidase, NADH oxidase) [23]. This is due
to the redox potential of flavonoids that are capable of redu-
cing highly oxidizing free radicals such as superoxide, peroxyl,
alkoxyl, and hydroxyl radicals by hydrogen atom donation.
They also have the action of chelating metal ions (iron, copper,
etc.), and inhibiting the synthesis of radicals [24,25], for exam-
ple, quercetin is known for its chelating properties and stabi-
lizing iron; catechins inhibit lipid peroxidation; epicatechin and
rutin are strong radical scavengers and inhibitors of lipid
peroxidation in vitro [26].
Flavonoids specifically act on the enzymatic functions of
the inflammatory process, inhibiting the release of histamines,
through the inhibition of phosphodiesterases, of the protein
kinases (PK), binding competitively with the ATP enzymes
associated with signal transduction and to the activation of
immunological mechanisms. The anti-inflammatory activity of
these bioactive compounds also occurs by modulating cells
involved with inflammation (inhibit proliferation of mast cells,
T cells, B cells, NK cells, and neutrophils) and the inhibition of
the synthesis of proinflammatory cytokines TNF-α (IL-1),
released by activated macrophages and several other cell
types, being responsible for the induction of apoptosis and
inhibition of the NF-κB pathway [27–33].
Another mechanism of action of flavonoids in the inflam-
matory process is through the inhibition of the activity of the
132 B. V. C. D. SOUZA ET AL.
enzymes of the arachidonic acid pathway, phospholipase A2
(PLA2), cyclooxygenase (COX), and lipoxygenase (LOX), redu-
cing the production of eicosanoids, and modulate expression
of nitric oxide synthase (iNOS), which results in the inhibition
of nitric oxide production [34–39]. The chemical structure of
these compounds is responsible for their anti-inflammatory
activity, such as C-ring unsaturation (2–3 positions), the num-
ber and position of hydroxyl groups, C-4 carbonyl (Ring B), and
glycosylation of the molecule. Some subclasses of flavonoids,
even without this structure, for example, aglone kaempferol,
are also notable for their activity on enzymes in the inflamma-
tion cascade [40].
Chronic inflammation is directly related to many diseases,
including cancer, allergies, arthritis, cardiovascular diseases,
and diabetes, and flavonoids due to their potent anti-inflam-
matory actions and antioxidants, as previously explained, have
been targets of new therapeutic strategies for these patholo-
gies [41].
Hyperglycemia in DM2 is caused by altered digestion and
absorption of dietary carbohydrate, glycogen storage deple-
tion, increased gluconeogenesis, pancreatic β-cell dysfunction,
peripheral tissue insulin resistance, and failures in insulin sig-
naling pathways. Flavonoids act as hypoglycemic agents by
reducing intestinal absorption of dietary carbohydrates, mod-
ulating the enzymes involved in glucose metabolism (inhibit-
ing α-glycosidase), improving β-cell function, and insulin
secretion and action, and by their properties as antioxidant
and anti-inflammatory agents [42,43].
Yeon, Bae, Kim and Lee [44] performed a study with 4186
participants, divided into two groups according to fasting
glycemia: normal fasting blood glucose (up to 100 mg/dl)
and fasting blood glucose ≥100 mg/dl who investigated the
association between flavonoid intake and risk of type 2 dia-
betes mellitus (DM2) and found that the intake of these bioac-
tive compounds was lower in the hyperglycemic group and
that insulin resistance had an inverse relationship to the intake
of flavones and flavonols among individuals confirming the
hypoglycemic effect.
In the patent US20130231492, in vivo tests were conducted
and the dosages were between 2ug/ml and 5ug/ml, in which
was found that flavone derivatives can significantly increase
the glucose consumption of hepatocellular carcinoma cells
(HepG2) insulin resistant, increase the absorption and utiliza-
tion of glucose, and promote the translocation of the glucose
transporter in the skeletal muscle cells (GLUT4) at different
levels. This last effect is one of the main mechanisms for the
diabetes treatment, providing the application of these bioac-
tive compounds for antidiabetic drug production [13,45].
Some of the compounds tested had comparable and/or
superior antidiabetic activity than the metformin, in addition
to a greater effect than insulin on GLUT4 translocation in
skeletal muscle cells. These researchers also elucidated one
of the molecular mechanisms of the antidiabetic effect of
flavonoid derivatives, which occurs by the activation of AMP-
activated protein kinase (AMPK), one [20–22], an enzyme that
acts on cellular metabolism, maintaining energy homeostasis
and inducing a cascade of intracellular events in response to a
change in the cellular energy load, being the same mechanism
of action by which metformin exerts its pharmacological
action. This cellular enzyme is stimulated by physical exercise,
so the prescription of diet and physical activity for individuals
with DM2 is closely related to the activation of AMPK, which
seems to be responsible for many beneficial effects in the
treatment and prevention of the disease [13,45–47].
Mokashi, Khanna and Pandita [48] also evaluated the flavo-
noids antidiabetic activity in insulin resistant HepG2 cells, and
obtained similar results to those of US20130231492 invention.
The researchers used this HepG2 cell line model to mimic the
in vivo condition of DM2. It was observed that flavonoid-
treated cells increased GLUT4 translocation to the cell mem-
brane, with consequent increase in glucose uptake, in addition
to a decrease in insulin resistance, confirming that flavonoids
represent a promising treatment for diabetes mellitus type 2.
3.2. Bauhinia forficata associated with other bioactive
compounds in the diabetes treatment
Bioactive compounds from medicinal plants have proven ben-
eficial effects on diabetes, improving glycemic control, lipid
profile, and antioxidant status. Such compounds may be alka-
loids, carbohydrates, glycosides, flavonoids, steroids, terpe-
noids, peptides and amino acids, lipids, phenolics,
glycopeptides, and iridoids [49,50].
Phytochemicals reduce blood glucose and prevent the
absorption of glucose from the gastrointestinal tract. This
hypoglycemic effect is due to increased insulin secretion
through pancreatic β-cell stimulation; glucagon hormone
resistance that increases blood glucose levels; increased num-
ber and sensitivity of insulin receptors; decreased glycogen
loss; increased consumption of glucose in tissues and organs;
insulinomimetic paper; elimination of free radicals; stimulation
to increase blood microcirculation, inhibition of α-glycosides
and other actions, such as reduction in intestinal transit
[51,52]. Hosseini, Shafiee-Nick and Ghorbani [53] reported
that the antidiabetic activity of some phytochemicals is
mediated by the inhibition of beta cell degeneration.
There are several medicinal plants with proven hypoglyce-
mic and antidiabetic effects, among them the Moringa oleifera,
Abelmoschus esculentus Lycium barbarum, Rourea cuspidata,
Gentiana olivieri, Bauhinia forficata, Eugenia jambolana,
Lactuca indica, Mucuna pruriens, Tocophera cordifolia,
Momordica charantia, Aporosa lindleyana, Myrtus communis,
and Terminalia pallida [54].
Fombang and Saa [55] have shown that Moringa oleifera
tea has antihyperglycemic and antioxidant activity in rat and
human models, being attributed to its content of polyphenols,
particularly phenolic acids, flavonoids, and tannins, which
inhibit α-amylase, α-glucosidase, and intestinal glucose
uptake; improve glucose uptake by peripheral tissues, sup-
press gluconeogenesis, and stimulate insulin secretion
[56–61].
A recent study confirmed the in vivo hypoglycemic activity
of okra (Abelmoschus esculentus L. Moench) in vivo, from which
the rhamnogalacturonan polysaccharide was extracted and its
hypoglycemic effect was tested in streptozotocin-induced dia-
betic rats, which showed a decrease in blood glucose level

and glucose tolerance [62]. Besides this activity, this bioactive
polysaccharide improves diabetic nephropathy and increases
the proliferation of splenocytes and the secretion of cytokines,
acting as an immunomodulator [63,64].
Lycium barbarum, a fruit that also has in its composition
bioactive polysaccharides, mainly mannose, rhamnose, glu-
cose, galactose, and xylose, inhibited the absorption of glu-
cose in vitro and may be a potent antidiabetic agent [65].
Another plant with activity with this activity is Rourea cuspi-
data, whose continuous administration of 200 mg/kg of its
hydroalcoholic extract, in vivo, significantly reduced the blood
glucose concentration of diabetic rats, with a similar effect to
glibenclamide, which acts stimulating the secretion of insulin
from β cells of the islets of Langerhans, and the hyperin,
present in this plant, may be the hypoglycemic agent, since
it has the capacity to increase glycolysis, due to the increase in
liver hexokinase activity and decrease activities of gluconeo-
genic enzymes [66–68].
Herwig, Corinna, Valerie, Doeclecio and Didier (JP2012102144;
JP2005504753; US20040170714; US2006018859; WO2003011311)
performed tests with several extracts of Bauhinia spp, which
showed hypoglycemic activity, and is an alternative for the dia-
betes treatment, acting as an oral hypoglycemic agent. This inven-
tion patented the extraction production methods, which
consisted in the use of an ethanol and water mixture as solvent
extractor of the compounds in the B. fortificata young leaves,
containing 30–70% of water. Besides the method of extraction, a
medicine and a food supplement based on Bauhinia extracts were
made [69].
The extract can be made from any aerial parts of the
Bauhinia species. However, the best results were found with
the extracts obtained from young leaves. Therefore, they were
chosen for the extracts production of this patent cited above,
and the extraction should preferably occur from the B. fortifi-
cata leaves.
The hypoglycemic activity found in this invention was simi-
lar to the effect obtained by drugs, such as metformin. This
effect is due to the combined action of different bioactive
compounds as flavones or flavonoids (isoquercetina, kaemp-
ferol, quercetin, rutin). Supplementation was done at a dosage
of 150 mg extract/kg of body weight, twice a day, resulting in
improved glucose tolerance and increased excretion thereof.
Another beneficial effect observed was the antioxidant action
of these extracts. In vitro and in vivo studies have shown that
oxidative stress decreases insulin secretion from pancreatic β
cells and interferes in the insulin signaling pathway, causing
insulin resistance and type 2 diabetes [70–74].
In the medicine formulation of the invention JP201210214,
in addition to Bauhinia extract (0.01–99%), it was added vita-
mins C and E, alpha-lipoic acid, flavonoids, glutathione, caro-
tenoids, coenzyme Q10, zinc, and selenium bound to the
proteins, to optimize the antioxidant activity of the drug. The
food supplement composition included vitamins, minerals,
probiotics, prebiotics, fatty acids, flavonoids, polysaccharides,
lipoic acid, and Bauhinia extract (0.01–99%).
Moffa and Calefe [75] have patented processes to obtain
concentrated herbal extracts for the product production for
type 2 diabetes treatment, obtained using it alone or in com-
bination with the concentrated B. forficata extracts and
EXPERT OPINION ON THERAPEUTIC PATENTS 133
Syzygium jambolanum (Jambolão) seeds, and prepared for
oral administration in the form of microgranules, pellets,
tablet, or powder.
The extracts of this invention were obtained by mixing, by
mass, 19% of Bauhinia leaves, 52.5% of alcohol, and 28.5% of
water, and between 9% and 19% of Jambolão seeds, 57–64%
of alcohol, and 24–27% of water. The amount of B. forficata
extract and S. jambolanum contained in the pellet was 1–90%.
The inventors of this BR1020150157690 patent tested these
extracts in streptozotocin-induced diabetic rats of the Wistar
line, for 42 days. These animals had their serum glucose levels
reduced to values similar to those observed in the animals of
the group that received metformin, and it was verified the
antidiabetogenic activity of the pellets with these vegetal
extracts.
The invention (US20140186321) was developed by Thomas
Christian Lines and relates to a method to treat metabolic
syndrome or diabetes by administering an effective amount
of a composition containing quercetin, vitamin B3, vitamins C
and B. fortificata extract. This composition may be a dietary
supplement or a pharmaceutical formulation, of which may be
presented in solid form (powder or tablet) or in liquid form
(beverage or syrup) [76].
According to this invention, the combination of quercetin
with B. fortificata potentiates the beneficial effects in patients
with DM2, because there is an increase in blood flow, con-
siderably reducing the risk of thrombotic events, lowering
blood pressure, and synergistically increasing sensitivity to
insulin. This composition may also be associated with a hypo-
glycemic drug or with the use of insulin to improve its efficacy,
allowing the individual to be treated with lower doses of the
drug and of the synthetic hormone. Therefore, there is a side
effects reduction (weight gain, nausea, hypoglycemia, diar-
rhea, flatulence, inappetence, liver damage, fluid retention,
and stomach pain). The developed formulation may be admi-
nistered concomitantly with the medication or at different
times before meals, at a dose of 100mg to 2g of quercetin
(preferably 250mg to 1g), and 50mg to 6g of B. fortificata
extract (preferably 125 mg to 0.5 g).
The US20060189512 patent [77] describes the develop-
ment of a dietary supplement, based on florizine extract, B.
forficate, and other plants which have hypoglycemic effects. In
addition to the glycemia reduction, glucose excretion and
reduction in postprandial insulin levels, it was also found
that this supplement facilitated weight loss and increased
longevity, decreasing the onset or incidence of aging-related
diseases.
The beneficial effects of this invention were enhanced by
the synergy of florizine extract administered with other ele-
ments. Such elements are quercetin, floretin, epicatechin, cate-
chins, chlorogenic acid, and other flavonoids. It was also found
that the association of this supplement with drugs for DM
treatment also potentiates its hypoglycemic effect. The
dosage of this dietary supplement should be 3 to 30 g per
day, administered in three separate doses, between 1 and
10 g, about 30 to 60 min before meals [77].
Another invention that has also used the B. forficata extract
associated with other compounds was developed by Fogel
(US20100202980; US20150190446; WO2009001362; IL202980;
134 B. V. C. D. SOUZA ET AL.
EP 2,170,360) [78]. This patent reports a plant-based composi-
tion of Urtica dioica, U. urens, U. pilulifera, Artemisia dracunculus,
A. alba, A. herba, A. roxburghiana, A. judaica, Morus alba, M.
bombycis, M. indica, M. insignis, M. nigra, M. austral, B. forficata,
Cinnamomum zeylanicum, C. saigonicum, C. aromaticum, C.
laurus, Canella winterana, Taraxacum officinale, and Rosa canina.
The referred composition can be a dietary supplement and
a pharmaceutical formulation, both with acceptable excipients
(maltodextrin, calcium phosphate, and aerosil), the presenta-
tions may be in the form of tea, tincture, tablet, capsule, pill,
bar, chewing gum, lotion, powder, or granules. The health
claims of this invention are for the DM2 treatment and/or
prevention and dyslipidemias and/or associated conditions,
and the therapeutic dose is from 1000mg to 6 g per day [78].
3.3. Bauhinia forficata in the diabetes treatment
Bauhinia forficata has several chemical constituents, especially
flavonoids, especially canpherolic and quercetin glycosides.
Among these, kaempferol 3,7-di-O-α-L-rhamnoside or kaemp-
feritrin is considered as the chemical marker for those of
leaves of B. forficata subsp forficata, since it is present in this,
but absent in B. forficata subsp. Pruinosa (Vogel) Fortunato &
Wunderlin [79–81].
Due to the presence of these bioactive compounds,
Bauhinia forficata exerts several activities beneficial to the
body as antioxidant, antidiabetic and hypoglycemic, anti-
inflammatory, antimicrobial, antitumor, anticoagulant, with
application in the treatment of diseases such as cancer, meta-
bolic syndrome, obesity, osteoporosis, Alzheimer’s, and dia-
betes [82].
Rolim et al (BR1020130241504) have patented an invention
which describes an effervescent pharmaceutical composition
for DM treatment based on the dry extract of Bauhinia for-
ficata. This formulation consisted of dry ethanolic extract of
Bauhinia forficata (15–70%), effervescent base (36–76%), citric
acid (6–12%), tartaric acid (10–24%), sodium bicarbonate (20–
40%), drying adjuvant (colloidal silicon dioxide) (10–30%),
sweetener (sucralose) (8–14%), a binder (polyvinylpyrrolidone),
and excipient (coloring, flavoring, diluent, disintegrating, lubri-
cating, wetting, absorbent). The effervescent pharmaceutical
composition can be presented as a powder, granule, or tablet,
being an alternative for diabetic patients [83].
Da Cunha et al. [84] carried out a study in diabetic-induced
rats by streptozotocin in which the hypoglycemic effects of
different B. forficata dry extracts were verified, using a single
dose of 200 mg/kg of body weight. After the administration of
B. forficata extracts, an average reduction of 47.29% of the
plasma glucose of these animals was observed.
Salgueiro et al. [85] investigated the effects of Bauhinia
forficata link subsp. pruinose tea, and its effect against oxida-
tive stress and liver damage in diabetic rats. The results
showed that B. forficata tea reduced oxidative stress, but did
not change glycemia, unlike previous studies. Thus, the
researchers inferred that the absence of the hypoglycemic
action of B. forficata tea may be due to the inactivation of
the compound kaempferitrin, the main substance responsible
for the hypoglycemic action, that may have been lost during
the infusion preparation.
A study conducted with pre-diabetic and diabetic
patients, who used a 0.15% dose of B. forficata infusion,
three times a day, after meals for 3 months, showed that
there was a significant reduction in the glycemia of these
patients, suggesting that tea of this species could be use-
ful in the prevention or complementary treatment of DM2
[86]. Another study with diabetic patients, who also used
the infusion of B. forticata, obtained a decrease in their
glycemic profile during the intervention period (75 days)
[87]. These results are similar to those verified by Zaccaron
[88], that evaluated blood pressure and fasting blood glu-
cose levels of all patients with DM2 from a Basic Health
Unit and found that the patients who took tea from the
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-
ciency of this herbal medicine in the treatment of this
pathology.
4. Conclusion
It was concluded that these patents highlight the different
products developed based on Bauhinia forficata and other
bioactive compounds used in the prophylaxis and treatment
of diabetes mellitus, especially type 2. The phytotherapic pro-
ducts studied have several advantages when compared to the
synthetic hypoglycemic drugs, because they control glycemia
without causing adverse effects. Besides, they have other
biological functional properties, such as antioxidant, hypoten-
sive, hypocholesterolemic, anticoagulant, and anti-inflamma-
tory activities. The researches demonstrate the growing
interest of the pharmaceutical industry and academies in the
development of hypoglycemic agents from natural products
for the diabetes mellitus treatment, to improve the quality of
life of the patients affected by this pathology.
5. Expert opinion
DM2 is a metabolic disorder characterized by chronic hyper-
glycemia, being a cardiovascular risk factor, with high morbid-
ity and mortality. Elevated postprandial glucose levels can
trigger the production of reactive oxygen species (ROS),
decrease insulin secretion and interfere with its signaling path-
way, as well as cause micro and macrovascular complications
[89–93].
The glycemic metabolism control in DM is necessary to
avoid the appearance of those complications. The body tries
to compensate the glucose excess and the constant insulin
resistance by increasing insulin production and secretion.
However, this compensatory mechanism cannot act continu-
ously, progressing to a systemic inflammation, and conse-
quently reduction in insulin secretion by β cells and their
apoptosis, leading to the disease progression [94,95].
Flavonoids have anti-inflammatory, antioxidant, and che-
mopreventive properties. In vitro and in vivo studies have
found that these compounds can eliminate free radicals and
chelators inducing oxidation, reducing the risk of cardiovascu-
lar diseases, lowering glycemia, and improving secretion and
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.
Based on this, the invention (US20130231492) tested fla-
vone derivatives in vivo and found that there was an increase
in the consumption, uptake, and utilization of glucose by
insulin resistant cells, and enabled GLUT4 translocation, prov-
ing that these compounds can be applied in the hypoglycemic
drugs production. In the patent (JP2012102144) were tested
hydroalcoholic extracts of B. forficata associated with vitamins
C and E, alpha-lipoic acid, glutathione, carotenoids, coenzyme
Q10, zinc, and selenium, which showed hypoglycemic and
antioxidant activity. From these results, a drug and a food
supplement were developed.
Other patented products for the DM treatment were micro-
granules, pellets, tablets, or powders with B. forficata extracts
of and Jambolão seeds [30], and a supplement and a pharma-
ceutical formulation with quercetin, vitamin B3, vitamins C and
B. fortificata extract [31].
Hypoglycemic dietary supplements based on B. forficata
and other phytotherapic plants have been presented in
patents (US20060189512; US20150190446). The invention
(BR1020130241504) relates to an effervescent pharmaceuti-
cal composition in the form of powder, granulate, or tablet
based on Bauhinia forficata dry extract. This invention dif-
fers from the others discussed previously, because it has a
composition in which the hypoglycemic effect is unique and
exclusively from the ethanolic B. forficata extract, while in
the other inventions there is the possibility of a therapeutic
combination between the Bauhinia extract and at least one
oral hypoglycemic agent, insulin, and other bioactive
compounds.
Thus, there are some inventions with B. forficata for the
DM2 treatment, and from the seven patents analyzed, two
did not perform preclinical tests, of which only
US20060189512; US20150190446 were tested in humans.
Therefore, B. forficata may be an effective adjuvant in the
treatment of this chronic disease and, with this patent
review, it is predicted to extend prospects for future
research on the DM treatment based on phytotherapic pro-
ducts, such as B. forficata, considering also the increasing
interest and investments in R & D in this area by the
pharmaceutical industries [100] (Table 1).
Funding
This research did not receive any specific grant funding from public,
private or nonprofit development agencies.
Declaration of interest
The authors have no other relevant affiliations or financial involvement
with any organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the manuscript
apart from those disclosed. Peer reviewers on this manuscript have no
relevant financial or other relationships to disclose
ORCID
Bárbara Verônica Cardoso de Souza http://orcid.org/0000-0002-0801-
0452
Grasielly Rocha Souza http://orcid.org/0000-0002-0801-0452
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