U.S. patent application number 15/524757 was filed with the patent office on 2017-09-07 for single herb extract for the treatment of pcos (poly cystic ovarian syndrome).
This patent application is currently assigned to PAWAN KUMAR GOEL. The applicant listed for this patent is PAWAN KUMAR GOEL. Invention is credited to Ashok SHARMA, Kiran TEWARI.
Application Number | 20170252391 15/524757 |
Document ID | / |
Family ID | 56127788 |
Filed Date | 2017-09-07 |
United States Patent
Application |
20170252391 |
Kind Code |
A1 |
SHARMA; Ashok ; et
al. |
September 7, 2017 |
SINGLE HERB EXTRACT FOR THE TREATMENT OF PCOS (POLY CYSTIC OVARIAN
SYNDROME)
Abstract
Discloses is a single herb extract for the treatment of PCOS
(Poly Cystic Ovarian Syndrome) when given in oral dosage form as
capsules of 500 mg, twice a day for period of time ranging from
30-90 days, The extract is obtained from fenugreek seeds using a
specific method of extraction and comprises five
furostanolicsaponins present in synergistic ratios as in Table 1
and having analytical profile as in FIG. 1.
Inventors: |
SHARMA; Ashok; (Panchkula,
IN) ; TEWARI; Kiran; (Panchkula, IN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
KUMAR GOEL; PAWAN |
|
|
US |
|
|
Assignee: |
KUMAR GOEL; PAWAN
PANCHKULA-(HARYANA)
IN
|
Family ID: |
56127788 |
Appl. No.: |
15/524757 |
Filed: |
February 11, 2015 |
PCT Filed: |
February 11, 2015 |
PCT NO: |
PCT/IN2015/000079 |
371 Date: |
May 5, 2017 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61P 43/00 20180101;
A61P 15/08 20180101; A61P 15/00 20180101; A61K 9/0053 20130101;
A61K 31/7048 20130101; A61K 36/48 20130101; A61K 9/48 20130101 |
International
Class: |
A61K 36/48 20060101
A61K036/48; A61K 9/48 20060101 A61K009/48; A61K 31/7048 20060101
A61K031/7048; A61K 9/00 20060101 A61K009/00 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 16, 2014 |
IN |
3718/DEL/2014 |
Claims
1. A single herb extract obtained from fenugreek seeds, for the
treatment of PCOS (polycystic ovarian syndrome) wherein the same
comprises a synergistic mixture of five furostanolicsaponins as
given in FIG. 1 and Table 1.
2. The herbal extract of claim I for treatment of PCOS wherein the
effective dosage is one gram per day in form of capsules of 500 mg
twice a day for a period of time ranging from 30-90 days, depending
upon individual response and clinical assessment.
Description
FIELD OF INVENTION
[0001] Invention pertains to a single herb extractfor the effective
treatment of PCOS (Poly Cystic Ovarian Syndrome) when given in oral
dosage form as capsules of 500 mg, twice a day for period of time
ranging from 30-90 days. The extract is obtained from the seeds of
a single herb viz. fenugreek, using a specific method of
extraction.
BACKGROUND OF INVENTION
[0002] About PCOS: Polycystic ovary syndrome (PCOS) is one of the
most common endocrine disorders among females. PCOS has a diverse
range of causes that are not entirely understood, but there is
evidence that it is largely a genetic disease. Polycystic ovary
syndrome (PCOS) is a problem in which a woman's hormones are out of
balance. It s commonly associated with failure of ovulation
Polycystic Ovary Syndrome (PCOS) is an endocrine disorder which
affects 10-15% of the female population. This syndrome represents
the most common hormonal disorder in women of reproductive age.
[0003] The symptoms and severity of the disease vary greatly among
women. In women with PCOS, the physiological hyperinsulinaemia of
adolescence may constitute a triggering factor that brings about
the development of hyperandrogenism and anovulation.
[0004] Causes: Polycystic ovary syndrome has a basic etiology
linked to an oxidative syndrome with insulin resistance. The
insulin resistance and consequent hyperinsulinaemia that are often
associated with this syndrome play an important role not only in
the pathogenesis of the syndrome itself, but also in the clinical
symptomatology. The chronic anovulation typical of PCOS results in
an increased number of atretic follicles (which become cysts) and
increased interstitial tissue in the stroma of the ovaries.
[0005] Mechanisms involved in PCOS: Under normal conditions, women
produce a single dominant follicle that participates in a single
ovulation each menstrual cycle. The process begins when a cohort of
primordial follicles is recruited to initiate growth. Successive
recruitment gives rise to the primary, secondary, tertiary and
graafian follicles present in the ovaries. The ability to become a
dominant follicle is not a characteristic shared by all follicles,
and those that lack the property die by atresia due to increased
androgens. In the human female, only about 400 of the original 7
million follicles survive atresia and give rise to dominant
follicles.
[0006] In patients with PCOS, the process of folliculogenesis does
not proceed normally. The initial steps, recruitment and growth to
the small graafian stages, are functioning in PCOS, but the
terminal step, the selection of dominant follicles that can
ovulate, does not occur regularly. Viable follicles seldom develop
beyond about the 6 mm stage. In some unexplained way, this
condition leads to the accumulation of large numbers of small
graafian follicles (commonly referred to as cysts) in which the
theca interstitial cells (TIC) produce abnormally large amounts of
androgen, but the granulosa cells (GC) fail to express the
aromatase enzyme and aromatize the androgen substrate to estradiol.
Consequently, a state of continued hyperandrogenism results. The
problem is self-perpetuating in part because the atretic follicle
becomes an androgenic follicle by a "default" mechanism: because of
low aromatase activity in atretic follicles, androstenedione is
preferentially metabolized to testosterone and hence to
dihydrotestosterone within the ovary (Poison et al (1988):
Polycystic ovaries--a common finding in normal women, The Lancet
Volume 331, Issue 8590, 16 Apr. 1988, Pages 870-872D01:
10.1016/S0140-6736(88)91612-1).
Diagnosis of PCOS
[0007] Gynecologic ultrasonography--specifically looking for small
ovarian follicles help to detect PCOS. Small ovarian follicles are
believed to be the result of disturbed ovarian function with failed
ovulation, reflected by the infrequent or absent menstruation that
is typical of the condition. In PCOS, there is a so-called
"follicular arrest"; i.e., several follicles develop to a size of
5-7 mm, but not further. No single follicle reaches the
preovulatory size (16 mm or more). [0008] Laparoscopic
examination--it may reveal a thickened, smooth, pearl-white outer
surface of the ovary. [0009] Increase in hormonal level--Serum
(blood) levels of androgens (male hormones), including
androstenedione and testosterone may be elevated. The free
testosterone level is thought to be the best measurewith .about.60%
of PCOS patients demonstrating supranormal levels. The ratio of LH
(Luteinizing hormone) to FSH (Follicle-stimulating hormone), when
measured in international units, is elevated in women with PCOS
[0010] Anti-Mullerian hormone (AMH) is increased in PCOS, and may
become part of its diagnostic criteria.
[0011] Treatment: Pharmaceutical medications which are prescribed
for PCOS include: [0012] i. Combination estrogen and progestin
hormones: birth control pills, vaginal rings, or skin patches.
These hormones correct irregular menstrual bleeding or absent
menstrual cycles. [0013] ii. Synthetic progestin: It makes
endometrial lining build up and shed. This shedding prevents
uterine cancer. [0014] iii. Androgen-lowering spironolactone
(Aldactone): Diuretic. It is often used with estrogen-progestin
therapy. [0015] iv. Metformin (Glucophage): This diabetes medicine
is a newer PCOS treatment for controlling insulin, blood sugar
levels, and androgen levels. [0016] v. Clomiphene (Clomid,
Serophene) (fertility medicines) and gonadotropin injections (LH
and FSH). [0017] vi. Medroprogesterone acetate [0018] vii.
Gonadotrophin releasing hormone agonists [0019] viii.
Glucocorticoids [0020] ix. Ketoconszole, flutamide, finasteride and
metformin. [0021] (Source:http://www.webmd.com)
[0022] However, none of the treatments is specific for the
effective treatment of PCOS as they include the combinations of
hormones to treat PCOS which have side effects also. So there is a
need to develop safer formulations e.g. from herbal extracts to
treat polycystic ovary syndrome.
Herbal Extracts for the Treatment of PCOS
Prior Art
[0023] US Patent Application No. 20070298049 (2003) discloses a
therapeutic agent for treating polycystic ovary syndrome (PCOS).
The agent comprises an extract of mushrooms as an active
ingredientwhich exhibits few, if any, side effects. It is effective
at inducing ovulation and is safely available for not only females
who desire to bear children, but also for unmarried or young
fernales.The present invention is different from this prior art
because it discloses an extract of furostanolicsaponins from
fenugreek seeds to be given orally for the effective treatment of
PCOS and does not contain any mushrooms or its extract at all.
[0024] US Patent Application No. 8062680 (2005) discloses a method
for treating Polycystic Ovary Syndrome in a patient wherein the
method comprising administering to the patient, together with
pharmaceutically acceptable excipients, a composition comprising
effective amounts of: natural herbs vizRhodiolarosea root extract,
Panaxquinquefollus root extract, Pfaffapaniculada, etc. In contrast
in the present invention, no such herbs are used at all. It is not
a mixture of herbs but extract obtained from seeds of a single herb
i.e. fenugreek.
[0025] WO Patent Application No. 2008119131 (2007) discloses a
composition for PCOS treatment comprising several herbs viz. Shu Di
Radix rehmanniae, Shan Yao Radix disocorea, Shan Yu Rou
Fructuscorniofficinalis etc. In contrast. in the present invention,
no such herbs are used at all. It is not a mixture of these herbs
but a well-defined extract obtained from seeds of a single herb
i.e. fenugreek.
[0026] CN Patent Application No. 102847081 (2011) discloses a
complex mixture of herbsfor PCOS treatment. However, the present
invention is not a complex mixture of the herbs but a well-defined
extract obtained from seeds of a single herb i.e. fenugreek.
Fenugreek is not disclosed at all in the prior art patent.
[0027] WO Patent Application No 2013136257 (2012) discloses an
herbal composition comprising a therapeutically effective amount of
the extract of a plant belonging to Calophyllum species as an
active ingredient and optionally, a pharmaceutically acceptable
carrier.The composition is formulated for oral administration in
the form of a tablet, capsule or granules used in the treatment of
a metabolic disorder like insulin resistance, hyperglycemia, type 2
diabetes, polycystic ovary syndrome or related. However in the
present invention an extract of furostanolicsaponins from fenugreek
seeds, is used which when given orally is effective in the
treatment of PCOS. Calophyllum species herbs are not used at all in
the present invention.
[0028] Articles
[0029] Wang et al (2007) have disclosed the use of cinnamon to
treat PCOS. The patients were exposed to cinnamon extracts orally
and they showed positive results(The effect of cinnamon extract on
insulin resistance parameters in polycystic ovary syndrome: a pilot
study Fertility and Sterility Volume 88, Issue 1, July 2007, Pages
240-243). In contrast, the present invention discloses use of
furostanolicsaponin extracts from fenugreek seeds, which when given
orally are effective in the treatment of PCOS. Cinnamon extracts
are not used in the present invention at all.
[0030] Ethan Basch et al (2003) has reviewed the therapeutic
applications of fenugreek. (Therapeutic Applications of Fenugreek,
Alternative Medicine Review Volume 8, Number 1, 2003. Pages 20-27).
Fenugreek and its extracts have been found to have good therapeutic
applications in the treatment of Diabetes and also lowering lipid
levels. The review does not disclose use of fenugreek extracts for
the treatment of PCOS specifically. Moreover, the extract of
fenugreek seeds as disclosed in the present invention is a
specific, analytically defined extract.
[0031] Kassem A. et al (2006) evaluated antifertility effect of
whole fenugreek seeds. In their study they exposed the rabbits to
feeding diets containing 30% fenugreek seeds. The seeds had
significant effect on the prebreeding estrogen concentrations in
the treated animals.(Evaluation of the potential antifertility
effect offenugreek seeds in male and female rabbits, Contraception
Volume 73, Issue 3, March 2006, Pages 301-306, DOI:
10.1016/j.contraception.2005.08.020). However, Kassem et al does
not disclose any formulation or fenugreek extract for the treatment
of PCOS specifically.
[0032] Bashtian M. H. et al (2013) discloses effects of fenugreek
seed extracts as adjuvant therapy with metformin, for the treatment
of woman with PCOS. It was a prospective randomized, double-blind,
placebo-controlled trial. Women were randomly allocated to receive
hydroalcoholic extract of fenugreek seeds in capsules (500 mg
dosage form) alongwith metformin (500 mg dosage form) and were
assessed for improvement. The results showed significant decrease
in PAO (polycystic appearing ovaries) in group. (Evaluation of
Fenugreek (Trigonellafoenum-graceum L.), Effects Seeds Extract on
Insulin Resistance in Women with Polycystic Ovarian Syndrorne, Iran
J Pharm Res. 2013 Spring; 12(2): 475-481).
[0033] The extract used in the study and its method of preparation
has been disclosed by Bashtiart as below:
[0034] Dried and fresh fenugreek seeds (25 Kg) were obtained from a
commercial source. Seeds were washed in distilled water and were
ground to a fine powder in a mixer under chilled conditions.
Obtained powder was extracted by percolated white ethanol (70%
w/w). The ethanol extract was lyophilized. The lyophilized extract
was 2600 g. Twenty-five percent of tricalcium phosphate was added
to dried extract. The powder mixture was crushed in a blinder and
passed through a 20-mesh sieve. A capsule-filling machine was used
thr preparation of powder containing capsules. The mean weight of
each capsule was 525 mg (500 mg dried extract). Placebo capsules
were filled (525 mg) with lactose powder colored with 1%
tartrazine
[0035] In contrast, the present invention is not a simple,
hydroalcoholic extract obtained from fenugreek seeds but a purified
extract of five furostanolicsaponins present in synergistic ratios
and obtained from fenugreek seeds by a proprietary process
developed by the inventor and for which the inventor has applied
for grant of patent in India vide patent application number
1439/DEL/2008 Dated Jun. 17, 2008 entitled "A NOVEL PROCESS FOR
EXTRACTION OF FUROSTANOLIC SAPONINS FROM FENUGREEK SEEDS" followed
by international patent application number--PCT/lN2008/000559,
subsequently filed and granted US patent number U.S. Pat. No.
8,217,165 B2 and divisional patent number U.S. Pat. No. 8,754,205
B2 , filed in EUROPE as application number EP 08 808 174. 0
[0036] Analytical fingerprint of the extract is given in Figo L The
composition of the extract is given below in Table 1.
TABLE-US-00001 TABLE 1 Composition of extract (LCMS fingerprint
given in FIG. 1) Peak Elution Time No. (Minutes) Compound Name % 1.
13.75 -- 7.13 2. 13.90 -- 4.61 3. 14.22 Trigoneoside IV a 15.10 4.
14.42 Glycoside F 29.36 5. 14.85 Protodioscin 43.80
[0037] Bashtian M. H. et al. does not anticipate the extract of
present invention, which is a specifically defined synergistic
extract of five furostanolicsaponins from fenugreek seeds, as per
Table 1 above. The significant differences between extract
disclosed by Bashtian et al. and that of present invention are as
per table below:
TABLE-US-00002 S. No. Bashtian M. H. et al (2013) Present invention
1. Discloses use of a hydroalcoholic Discloses use of an
analytically extract from fenugreek seeds.
definedfurostanolicsaponin extract purified from fenugreek seeds by
a proprietory process developed by the inventor for which inventor
has been granted patent. 2. The extract is used for PCOS The
extract is not used as adjuvant therapy and treatment as adjuvant
therapy therapeutic effect is obtained without use of any alongwith
metformin. metformin 3. The ingredients of the extract are
Ingredients are a well-defined mixture of five not known at all.
furostanolicsaponins present in synergistic ratios (FIG. 1 and
Table 1) 4. Quality of the extract cannot be Quality of the extract
is controlled owing to use controlled in absence of marker of
marker compounds and development of compounds. analytical
fingerprint (FIG. 1, Table 1)
[0038] Thus, none of the prior art anticipates use of the specific
extract of present invention which is obtained from the seeds of a
single herb viz. fenugreek and is comprising five
furostanolicsaponins present in synergistic ratios and extracted
from fenugreek seeds by a in proprietary process developed by the
inventor. The analytical profile (LCMSfingerprint) of the extract
is given in FIG. 1. The extract when given orally is effective in
the treatment of PCOS, at a dose of two capsules of 500 mg each for
a period of time varying between 30-90 days, depending upon
individual response and clinical assessment.
OBJECTS OF THE PRESENT INVENTION
[0039] It is an object of the present invention to disclose a
herbal extract obtained from a single herb viz. fenugreek which is
effective in the treatment of PCOS when taken orally.
[0040] Another object of the present invention is to disclose a
herbal extract for the treatment of PCOS comprising
fivefurostanolicsaponinspresent in synergistic ratios and obtained
from fenugreek seeds.
[0041] Yet another object of the invention is to disclose an oral
composition obtained from extract of fenugreek seeds which leads to
reduction in ovary volume, reduction in cyst size, complete
dissolution of cyst and increased chances of pregnancy in infertile
females.
[0042] A last object of the present invention is to disclose a
method of treatment of PCOS comprising administering the said
extract at a dosage of 1 gram per day in form of capsules of 500 mg
twice a day, for a period of time ranging from 30-90 days,
depending upon individual response and clinical assessment.
SUMMARY OF THE INVENTION
[0043] The invention discloses a single herb extract for the
effective treatment of PCOS (Poly Cystic Ovarian Syndrome) when
given in oral dosage form as capsules of 500 mg, twice a day for
period of time ranging from 30-90 days. The extract is obtained
from the seeds of fenugreek using a specific method of extraction
and comprises five furostanolicsaponins present in synergistic
ratios as in Table 1 (Page 7) and having analytical profile as in
FIG. 1.
DESCRIPTION OF THE ACCOMPANYING DRAWINGS
[0044] FIG. 1: Analytical fingerprint (LCMS profile) of extract of
five furostanolicsaponins from fenugreek seeds
DETAILED DESCRIPTION OF THE INVENTION
[0045] The present invention discloses a
furostanolicsaponinsextract comprising a synergistic mixture of
five compounds, obtained from fenugreek seeds and suitable for the
treatment of PCOS when given orally. The composition of the extract
is given in Table 1 above and the analytical profile is disclosed
in FIG. 1.
[0046] Dosage
[0047] Dosage forms of the above formulation were prepared in form
of 500 mg capsules of the powder. Same were evaluated for clinical
efficacy in the treatment of PCOS, after due approval of the
ethical committee. Dosage given was 2 capsules per day, morning and
evening after meals. Duration of administration of the extract
varied between 30 days to 90 days (3 months). Number of subjects
participating in the study was 50 and age group was
18-45years.Results of the treatment are given below:
TABLE-US-00003 TABLE 2 Overall patient response using oral dosage
form of present invention No. of % of patients responded to
Parameter Patients % treatment Pregnant Patients 6 12 94% Patients
with 18 36 (12 + 36 + 46) Complete dissolution of Cyst Reduced cyst
size 23 46 No Response 3 6 Total Patients 50 100
TABLE-US-00004 TABLE 3 Effect of oral dosage form of present
invention on menstrual cycle At the time of enrolment most of the
patients had prolonged menstrual cycle (81%) and irregular cycle
(10%). A few patients (10%) had primary infertilities. Menstrual
Visits Cycle Baseline 1 visit 2visit 3.sup.rd visit Total Irregular
2 2 1 0 5 Cycles 9.52% 9.52% 4.76% 0.00% 5.95% Primary 2 2 2 2 8
infertilities 9.52% 9.52% 9.52% 9.52% 9.52% Prolonged 17 17 11 4 49
Cycles 80.95% 80.95% 52.38% 19.05% 58.33% Regular 0 0 7 15 22
Cycles 0.00% 0.00% 33.33% 71.43% 26.19% Total 21 21 21 21 84 100.0%
100.0% 100.0% 100.0% 100.0%
[0048] There was significant improvement in menstrual cycle with
consumption of the fenugreek seed extract. On completion of the
last visit 71% of patient had regular cycles, 19% patient reported
prolonged cycle and approximately 10% reported primary
infertility.
[0049] Results of the study are summarized below: [0050] a.
Fenugreek seed extract of present invention caused significant
reduction in ovary volume in patients of PCOS. [0051] b. 46% of
study population showed reduction in cyst size [0052] c. 36% % of
study population showed complete dissolution of cyst [0053] d. 12%
of patients got pregnant [0054] e. 71% of patients reported regular
menstrual cycle on completion of the treatment [0055] f. Overall
94% of patients responded positively or got benefitted from the
fenugreek extract dosing.
[0056] Safety Profile
[0057] Safety profile of the extract was evaluated. No significant
changewere observed in serum liver function tests, serum renal
function tests and hemograms in the patients. It was concluded
based on the clinical results that administration of analytically
defined extract of present invention, at a dosage of 500 mg twice a
dayfor periods varying between 30-90 days, provided effective
results in the treatment of PCOS.
[0058] Method of Use of the Invention
[0059] The extract is made into dosage forms of capsules of 500 mg
each. When administered orally twice a day for periods varying
between 30-90 days, the extract provided effective results in the
treatment of PCOS.
[0060] Novelty--The invention discloses a novel herbal extract
derived from a single herb and its method of use for the treatment
of PCOS which has not been disclosed in the prior art. The extract
comprises a synergistic mixture of five furostanolicsaponins
extracted from seeds of a single herb viz. fenugreek (Table 1 at
Page 7 and FIG. 1). The extract when given orally at a dose of 1
gram per day (500 mg capsules, twice a day) for a period of time
ranging from 30-90 daysis effective in the treatment of PCOS.
[0061] Inventive step--The inventive steps lies in the technical
advancement of knowledge for treatment of PCOS using extract
obtained from a single herband disclosure of its method of use
(dosage per day for a fixed period of time i.e. 1 gram per day in
form of 500 mg capsules, taken twice a day for period ranging from
30-90 days, as per clinical advise and assessment based on patient
response). The novel extract is isolated from seedsof a single herb
viz. fenugreek and comprises a synergistic mixture of five
furostanolicsaponins(Table 1 at Page 7 and FIG. 1) which are
effective in the treatment of PCOS when given in appropriate
dosage.
[0062] Industrial application--The said extract is suitable for the
treatment of PCOS and can be manufactured on industrial scale.
[0063] Although the invention has been described with reference to
specific embodiments, this description is not meant to be construed
in a limiting sense. Various modifications of the disclosed
embodiments, as well as alternate embodiments of the invention,
will become apparent to persons skilled in the art upon reference
to the description of the invention and best mode of performing the
invention. It is therefore contemplated that such modifications can
be made without departing from the spirit or scope of the present
invention as defined and will be regarded within the scope of the
present invention.
* * * * *
References