U.S. patent application number 09/819828 was filed with the patent office on 2001-12-27 for herbal composition and method of manufacturing such composition for the management of gynecological disorders.
Invention is credited to Duggal, Ramesh Kumar, Katiyar, Chandra Kant, Rao, Bodapati Venkata Jagannadha.
Application Number | 20010055625 09/819828 |
Document ID | / |
Family ID | 11097044 |
Filed Date | 2001-12-27 |
United States Patent
Application |
20010055625 |
Kind Code |
A1 |
Katiyar, Chandra Kant ; et
al. |
December 27, 2001 |
Herbal composition and method of manufacturing such composition for
the management of gynecological disorders
Abstract
A herbal composition enriched with Plant coagulate for the
management of Gynecological disorders is envisioned. Also disclosed
is a process which involves selective solvent extraction of crude
herbs in contrast to conventional aqueous extraction to improve the
efficacy. The extract prepared by this method, enriched with Plant
coagulate is useful in the management of Gynecological disorders
and to prevent/treat anaemia due to excessive bleeding associated
with menstrual disorders.
Inventors: |
Katiyar, Chandra Kant;
(Delhi, IN) ; Duggal, Ramesh Kumar; (Delhi,
IN) ; Rao, Bodapati Venkata Jagannadha; (Delhi,
IN) |
Correspondence
Address: |
KING & SPALDING
191 PEACHTREE STREET, N.E.
ATLANTA
GA
30303-1763
US
|
Family ID: |
11097044 |
Appl. No.: |
09/819828 |
Filed: |
March 28, 2001 |
Current U.S.
Class: |
424/725 ;
424/734; 424/756 |
Current CPC
Class: |
A61K 2300/00 20130101;
A61K 36/00 20130101; A61P 5/00 20180101; A61K 36/00 20130101; A61P
15/02 20180101 |
Class at
Publication: |
424/725 ;
424/734; 424/756 |
International
Class: |
A61K 035/78 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 28, 2000 |
IN |
344/DEL/2000 |
Claims
We Claim:
1. A herbal composition for treating gynecological disorders, and
other related disorders, comprising a solvent extracted herbal
extract and a Plant coagulate made substantially from green leaves
of Spinach (Spinacia oleracea), Amaranth (Amaranthus spp.), Berseem
(Trifolium alaxandrum) and Cowpea (Vigna sinensiss), or any
combination thereof.
2. A herbal composition as claimed in Claim 1 wherein the herbal
extract comprises at least the following herbs:
10 S.NO. Common Name Botanical Name 1. Ashoka Saraka indica 2.
Lodhra Symplocos racemosa 3. Dhataki Woodfordia fruticosa 4.
Mustaka Cyperus rotundus 5. Sunthi Zingiber officinale 6. Darvi
Berberis aristata 7. Utpala Nelumbo nucifera 8. Haritaki Terminalia
chebula 9. Bibhitaki Terminalia belerica 10. Amalaki Emblica
officinalis 11. Amarasthi Mangifera indica 12. Jiraka Cuminum
cyminum 13. Vasaka Adhatoda vasica 14. Chandana Pterocarpus
santalinus 15. Pippali Piper longum
3. The composition of claim 1, wherein the herbal extract and the
Plant Coagulate is present in the composition in the range of
35-55%w/w and 45-65%w/w, respectively.
4. The composition of claim 2, wherein the herbal extract and the
Plant coagulate is present in the composition in the range of
35-55%w/w and 45-65%w/w, respectively.
5. The composition of claim 1, wherein the herbal extract comprises
the following herbs in the following ranges:
11 S.NO. Common Name Botanical Name Range 1. Ashoka Saraka indica
1100-2100 mg 2. Lodhra Symplocos racemosa 30-400 mg 3. Dhataki
Woodfordia fruticosa 40-300 mg 4. Mustaka Cyperus rotundus 5-30 mg
5. Sunthi Zingiber officinale 5-30 mg 6. Darvi Berberis aristata
5-30 mg 7. Utpala Nelumbo nucifera 5-30 mg 8. Haritaki Terminalia
chebula 5-30 mg 9. Bibhitaki Terminalia belerica 5-30 mg 10.
Amalaki Emblica officinalis 5-30 mg 11. Amarasthi Mangifera indica
5-30 mg 12. Jiraka Cuminum cyminum 5-30 mg 13. Vasaka Adhatoda
vasica 5-30 mg 14. Chandana Pterocarpus santalinus 5-30 mg 15.
Pippali Piper longum 5-30 mg
6. The composition of claim 1, wherein the composition is
formulated into a suitable dosage form such as solid dosage forms
like tablets, capsules/Liquid dosage forms like syrup, suspension,
emulsion, or elixir.
7. A process for the manufacture of a novel herbal composition for
treating gynecological and related disorders comprising: a) making
a coarse powder of the herbs Saraca indica, Emblica officinalis,
Terminalia chebula, Terminalia belerica, Zingiber officinale,
Cyperus rotundus, Pterocarous santalimus, Beriberis aristata,
Cuminum cyminum, Adhatoda vasika, Nelumba nucifera and Piper
longum, extracting the said coarse powder with high polar solvent
to obtain a decoction, filtering the decoction and collecting the
filtrate in a storage tank, concentrating the total filtrate to a
dry powder; b) separately making a coarse powder of the herbs
Symplocos racemosa, Woodfordia fruticosa and Mangifera indica,
extracting the coarse powder in a blended solvent comprising water
and an organic solvent to obtain an extract, concentrating the said
extract; c) extracting the juice of the leaves of one or more of
the herbs selected from the group consisting essentially of Spinach
(Spinacia oleracea), Amaranth (Amaranthus spp.), Berseem (Trifolium
alaxandrum) and Cowpea (Vigna sinensiss), or any combination
thereof, and separating the protein by a suitable method, followed
by filtration and drying of the coagulate, to obtain the plant
coagulate; and d) mixing the extracts obtained in steps a) and b)
and the Plant coagulate obtained in step c) to obtain the Herbal
composition of the present invention.
8. The process of claim 7 wherein the solvent employed for the
extraction of the coarse powder of the herbs in step a) is selected
from the group consisting essentially of water and alcohol.
9. The process of claim 7 wherein in step b) the organic solvent is
alcohol and water wherein the alcohol is used in a defined ratio
ranging from 1:9 or 9:1.
10. The process of claim 7 wherein in step c) the proteins are
separated by heating the juice to between 40-100.degree. C.
Description
PRIORITY APPLICATION
[0001] The present application claims priority under the Paris
Convention to Indian patent application entitled, "A Herbal
Composition and Process for the Manufacture of such Composition for
the Management of Gynecological Disorders," filed on Mar. 28, 2000
and assigned Indian Application Ser. No. 344/Del/2000.
FIELD OF INVENTION
[0002] The present invention is a herbal composition enriched with
plant coagulate for the management of gynecological disorders and a
process for the manufacture of such composition. In one embodiment,
the herbal composition includes selected herbs in predetermined
ratio ranges in combination with plant coagulate. The method of
manufacture involves selective solvent extraction of crude herbs,
in contrast to conventional aqueous extraction, to improve
efficacy. The extract prepared by this method, enriched with plant
coagulate, is useful in the management of Gynecological disorders
and to prevent/treat anaemia due to excessive bleeding associated
with menstrual disorders.
BACKGROUND OF INVENTION
[0003] Gynecology pertains to diseases of the female, but the term
is generally used for diseases related to the female genital
organs. Menstrual disorders such as dysfunctional uterine bleeding,
dysmenorrhoea, irregular periods and pre-menstrual syndrome are
common clinical problems in Gynecology.
[0004] Dysfunctional uterine bleeding (DUB) is defined as abnormal
bleeding from the uterus in the absence of organic disease of the
genital tract. Bleeding that occurs at intervals less than 21 days
or more than 36 days, lasts longer than 7 days, or involves blood
loss greater than 80 ml is considered abnormal. Dysfunctional
uterine bleeding is characterized by menorrhagia (excessively
profuse or prolonged uterine bleeding occurring at regular
intervals), metrorrhagia (irregular, acyclic uterine bleeding
occurring at frequent intervals), menometrorrhagia (excessive
uterine bleeding occurring at irregular intervals), and
polymenorrhea (bleeding occurring at regular intervals of less than
21 days). Potential causes of abnormal bleeding are numerous and
include, but are not limited to, menopause, pregnancy, endometrial
cancer, or fibromyomata, and thus the diagnosis of DUB must be made
after careful investigation to exclude these other causes (Galle et
al., Postarad Med, 93(2), 73-76 (1993)). Dysfunctional uterine
bleeding is divided into anovulatory and ovulatory types. In most
cases DUB is associated with anovulation (Bayer et al., JAMA,
269(14), 1823-1828 (1993)). Abnormal bleeding occurs in anovulatory
cycles because of oestrogen withdrawal or oestrogen breakthrough
bleeding. Oestrogen breakthrough bleeding occurs when there is
continuous oestrogen stimulation of the endometrium not interrupted
by cyclical progesterone secretion and withdrawal.
[0005] There are two approaches for the management of Gynecological
problems--conservative and surgical. Conservative approach includes
hormonal treatment with estrogenic or progestational agents (Bayer
et al., JAMA, 269(14), 1823-1828 (1993)), nonsteroidal
anti-inflammatory drugs and/or treatment with Ayurvedic
preparations.
[0006] The constraints with the hormonal treatment and NSAID are
tabulated (U.S. Pat. No. 5,552,416, Sep. 3, 1996; Shaw's textbook
of Gynecology, 319, 1992)
1 THERAPY OBJECTIVE(S) LIMITATION(S) GnRH agonists Blocks oestrogen
By injection secretion at Accelerates osteoporosis pitutary axis
level Limited to preoperative use Side effects Oral Progestagens
Corrects oestrogen and Limited effectiveness Progestagen ratio Side
effects Nonsteroidal Local endometrial Limited effectiveness
Anti-inflammatory actions Non-specific agent Agents Side effects
Oestrogen To raise blood Risk of developing oestrogen level
carcinoma of breast and endometrium
[0007] Because of the side effects of the hormones and NSAIDS,
physicians are looking for alternative options for treatment with
minimum side effects.
[0008] (1) Ayurvedic literature suggests the use of herbs such as
Saraca indica Linn. (Ashoka) (Bhavaprakasa Nighantu, ninth edition,
500-501 (1993)), Symplocos racemosa Roxb.(Lodhra) (Bhavaprakasa
Nighantu, ninth edition, 128-130 (1993)), Woodfordia fruticosa
kurtz (Dhatki pushpa) (Bhavaprakasa Nighantu, ninth edition,
109-110 (1993)) etc. in the treatment of gynecological
disorders.
[0009] (2) Saraca indica Linn. was studied for its uterine activity
to understand its phenomenal use in gynecological conditions
(Satyavati et al., Indian J Med Res, 58, 7 July, 1970).
[0010] (3) The following citations of different herbs exemplify
known roles of herbs in the management of gynecological
conditions.
[0011] (i) In Pradara (meno-metrorrhagia) one should take cold milk
boiled with the decoction of ashoka bark. (Vrndamadhava
63.5)(Classical uses of Medicinal Plants by P. V. Sharma, 27,
1996).
[0012] (ii) Symplocos racemosa Roxb. in combination with sugar is
recommended in the treatment of menorrhagia and other uterine
disorders (The Wealth of India, Vol. X, 90, 1976).
[0013] (iii) Lodhra is useful in women's diseases (Classical uses
of Medicinal Plants by P. V. Sharma, 333, 1996).
[0014] (a) In the eighth month, by taking Lodhra, Pippali and honey
mixed together with milk, fetal movement becomes normal
(Harita-samhita.3.50.5)- .
[0015] (b) Lodhra and Alabu leaves in equal parts should be pounded
and applied as paste in the vagina in order to treat gynecological
conditions. (Bhavaprakasa.ci.70.12).
[0016] (c) Lodhrasava is a popular herbal formulation for the
treatment of women's diseases.
[0017] (iv) Woodfordia fruticosa kurtz. is used in bowel complaints
and haemorrhages and is also administered in menorrhagia and
seminal weakness (The Wealth of India, Vol. X, 586-587, 1976).
[0018] (v) Dhataki pushpa is used in Leucorrhoea and for conception
(Classical uses of Medicinal Plants by P. V. Sharma, 204,
1996).
[0019] (a) Powder of Dhataki or Amlaki in an amoutn of 10 gm mixed
with profuse honey should be used in Leucorrhoea (Vrandamadhava
63.4).
[0020] (b) Nilotpala mixed with dhataki flowers and honey is used
in the morning hours to ensure conception (Gadanigraha 6.59).
[0021] (vi) Mangifera indica (Amrasthi) is used in slackness of
vagina (Classical uses of Medicinal Plants by P. V. Sharma, 40,
1996).
[0022] (a) Paste is made from mango seed (Kernel), honey and
camphor and applied to vagina in order to make the vagina
contracted and firm. (Sarangadhara-samhita.3.11.11)
[0023] (4) Ashokarishta, a classical ayurvedic fermented product
has been used to treat menstrual disorders. (Bhaishajya Ratnavali,
704, 1988).
[0024] Based on the long history of using herbs as cited above,
many Ayurvedic classical and proprietary formulations contain these
herbs for the treatment of gynecological problems.
[0025] There are limitations, however, to using these formulations
and, therefore, there exists room to improve upon them. Below is a
description of limitations present in the prior art.
[0026] (1) First, it is conventional practice to perform an aqueous
extraction of crude herbs for the manufacture of Ayurvedic
preparations. This, however, often results in the incomplete
extraction of actives present in the plants, due to their poor
solubility in water. For instance, commonly occurring plant
flavonoids have estrogenic activity (Miksicek R J, Mol Pharmacol
1993, Jul.;44(1): 37-43). Even the herbs containing flavonoids are
traditionally extracted with water in the manufacture of many
Ayurvedic preparations. This results in lesser flavonoid content in
the extract and hence is expected to show less activity.
[0027] (2) Second, the patients suffering from menstrual disorders
are likely to develop anemia due to excessive bleeding. Commonly,
there is a need to treat both the problems simultaneously.
Unfortunately, most of the Ayurvedic preparations are designed to
tackle menstrual problems ignoring the prophylactic treatment for
anemia.
[0028] Plant coagulate mainly finds its application as a food
supplement. The nutritional profile of plant coagulate includes
protein, fat, carbohydrates, vitamins such as carotene, niacin,
etc. and minerals such as calcium, phosphorous, magnesium,
potassium, zinc, copper and iron.
[0029] Several publications claim the successful use of Plant
coagulate in the management of malnutrition, especially in children
(Shah F H et al., Qual Plant Foods Hum Nutr., 30, 245;1981; Mathur.
B et al., Recent Advances in Nutriology, Volume I, 54A.).
[0030] Mathur. B et al., The Ind Nutr Diete., 26, 267; 1989, has
shown the usefulness of Plant coagulate in improving hemoglobin
levels in children.
[0031] (3) Third, the dose of classical liquid formulations is high
and palatability is less due to an astringent taste and insitu
alcohol.
SUMMARY OF THE INVENTION
[0032] The present invention discloses a novel herbal composition
and a process to make an herbal extract to enhance the efficacy in
treating gynecological disorders, in particular menstrual
disorders. The process involves combining aqueous and organic
solvent extracts of selective plants contained in the composition
to perform better than conventional aqueous extract.
[0033] In one embodiment of the invention, twelve herbs are
extracted with water and three herbs, which are rich in flavonoids,
are extracted with 75% alcohol to get maximum flavonoid content and
the extracts are then combined. The combined extract is compared
with the conventional aqueous extract for their Uterotonic
activity.
[0034] The combined extract obtained by this process is enriched
with plant coagulate prepared by a heat coagulation method to make
an herbal composition for the simultaneous treatment of
gynecological conditions and resultant anemia due to excessive
bleeding.
[0035] An effective amount of the herbal extract enriched with
plant coagulate and conventional extract are formulated into a
suitable dosage form and the improved efficacy of the herbal
extract prepared by this novel process is proven by a clinical
study.
DETAILED DESCRIPTION OF THE INVENTION
[0036] The present invention includes the preparation of herbal
extracts by selective solvent extraction of crude herbs to improve
the efficacy of the extract. The herbal extract prepared by this
method is enriched with plant coagulate to make an herbal
composition for the treatment of gynecological disorders.
[0037] In one embodiment, the activity of herbal extracts in the
treatment of gynecological disorders is observed when the following
active ingredients, both individually and in varying combinations,
optionally present in the following ranges, or in other ranges that
achieve the desired result.
2 S.NO. Common Name Botanical Name Range 1. Ashoka Saraka indica
1100-2100 mg 2. Lodhra Symplocos racemosa 30-400 mg 3. Dhataki
Woodfordia fruticosa 40-300 mg 4. Mustaka Cyperus rotundus 5-30 mg
5. Sunthi Zingiber officinale 5-30 mg 6. Darvi Berberis aristata
5-30 mg 7. Utpala Nelumbo nucifera 5-30 mg 8. Haritaki Terminalia
chebula 5-30 mg 9. Bibhitaki Terminalia belerica 5-30 mg 10.
Amalaki Emblica officinalis 5-30 mg 11. Amarasthi Mangifera indica
5-30 mg 12. Jiraka Cuminum cyminum 5-30 mg 13. Vasaka Adhatoda
vasica 5-30 mg 14. Chandana Pterocarpus santalinus 5-30 mg 15.
Pippali Piper longum 5-30 mg
[0038] Below is one example of the steps that may be followed to
manufacture the herbal compositions of the present invention. One
of ordinary skill in the art would understand that certain
substitutions may be made for any traditional laboratory techniques
described below.
[0039] Step I: Some of the herbs in the composition are preferably
Saraca indica, Emblica officinalis, Terminalia chebula, Terminalia
belerica, Zingiber officinale, Cyperus rotundus, Pterocarous
santalimus, Beriberis aristata, Cuminum cyminum, Adhatoda vasika,
Nelumba nucifera and Piper longum. They are coarsely powdered in a
suitable cutting mill. The coarse powder is extracted with a high
polar solvent preferably with sufficient water (approx. 4-10 times
the quantity of powder) using suitable equipment, preferably in a
open boiling pan. Once the extraction is over, the decoction is
filtered through suitable filtering medium and collected in a
storage tank. The herbs are again extracted with water (approx. 3-8
times) for a second time and the filtrate is collected into the
storage tank. The total filtrate is concentrated to dry powder
using suitable equipment like concentration pan, falling film
evaporator, at atmospheric pressure or under vacuum, and/or tray
drier, or by spray drying process. The extract may have a moisture
content of 3-8%w/w.
[0040] Step II: Some of the herbs in the composition, preferably
Symplocos racemosa, Woodfordia fruticosa and Mangifera indica, are
coarsely powdered using a cutting mill. In order to effect the
extraction procedure, the coarse powder is extracted in a blended
solvent that includes water and an organic solvent, preferably
alcohol in a defined ratio varying between 1:9 and 9:1 in a
suitable apparatus. The extract obtained is concentrated in
suitable equipment at atmospheric pressure or under vacuum.
[0041] Step III: The dry extracts obtained in step I & step II
are mixed well. The combined extract was studied for the Uterotonic
activity in comparison to conventional aqueous extract.
[0042] Step IV: Plant coagulate claimed to be useful in the
treatment of iron deficiency conditions is added to the herbal
extract prepared by the novel method to manage anemia associated
with menstrual disorders. Plant coagulate may be prepared from any
plant source and/or combined plant source. In this study, plant
coagulate is prepared from any single plant or combination of two
or more plants comprising mainly green leaf matter, preferably
among spinach (Spinacia oleracea), Amaranth (Amaranthus spp.),
Berseem (Trifolium alaxandrum) and Cowpea (Vigna sinensiss) by a
suitable method, preferably heat coagulation.
[0043] The herbal composition comprising the herbal extract
prepared by the novel process and Plant coagulate is formulated
into a suitable dosage form. The increased efficacy of these
formulations against conventional aqueous extract formulation, in
the treatment of gynecological disorders and the resultant anemia
due to excessive bleeding has been confirmed by a clinical
study.
[0044] In one aspect according to the present invention, the active
composition according to the present invention is formulated
preferably in admixture with a pharmaceutically acceptable carrier.
In general, it is preferable to administer the pharmaceutical
composition in orally administrable form, but formulations may be
administered via parenteral, intravenous, intramuscular,
transdermal, buccal, subcutaneous, suppository or other route.
Intravenous and intramuscular formulations are preferably
administered in sterile saline. One of ordinary skill in the art
may modify the formulation within the teachings of the
specification to provide numerous formulations for a particular
route of administration without rendering the compositions of the
present invention unstable or compromising its therapeutic
activity. In particular, a modification of a desired composition to
render it more soluble in water or other vehicle, for example, may
be easily accomplished by routine modification (salt formulation,
esterification, etc.).
[0045] The amount of active composition included within
therapeutically active formulations, according to the present
invention, is an effective amount for treating gynecological
conditions. For purposes of the present invention, a
prophylactically or preventively effective amount of the
compositions, according to the present invention, falls within the
same concentration range for therapeutically effective amount and
is usually the same as a therapeutically effective amount.
[0046] Administration of the active composition may range from
continuous (intravenous drip) to several oral administrations per
day (for example, Q.I.D., B.I.D., etc.) and may include oral,
topical, parenteral, intramuscular, intravenous, subcutaneous,
transdermal (which may include a penetration enhancement agent),
buccal and suppository administration, among other routes of
administration. Enteric-coated oral tablets may also be used to
enhance bioavailability and stability of the composition from an
oral route of administration. The most effective dosage form will
depend upon the pharmacokinetics of the particular agent chosen, as
well as the severity of the condition in the patient. Oral dosage
forms are particularly preferred, because of ease of administration
and prospective favorable patient compliance.
[0047] To prepare the pharmaceutical compositions according to the
present invention, a therapeutically effective amount of the herein
described composition according to the present invention is
preferably mixed with a pharmaceutically acceptable carrier
according to conventional pharmaceutical compounding techniques to
produce a dose. A carrier may take a wide variety of forms
depending on the form of preparation desired for administration,
e.g., oral or parenteral. In preparing pharmaceutical compositions
in oral dosage form, any of the usual pharmaceutical media may be
used. Thus, for liquid oral preparations such as suspensions,
elixirs and solutions, suitable carriers and additives including
water, glycols, oils, alcohols, flavoring agents, preservatives,
coloring agents and the like may be used. For solid oral
preparations such as powders, tablets, capsules, and for solid
preparations such as suppositories, suitable carriers and additives
including starches, sugar carriers, such as dextrose, mannitol,
lactose and related carriers, diluents, granulating agents,
lubricants, binders, disintegrating agents and the like may be
used. If desired, the tablets or capsules may be enteric-coated for
sustained release by standard techniques. The use of these dosage
forms may significantly impact the bioavailability of the
composition in the patient.
[0048] For parenteral formulations, the carrier will usually
comprise sterile water or aqueous sodium chloride solution, though
other ingredients, including those which aid dispersion, also may
be included. Where sterile water is to be used and maintained as
sterile, the compositions and carriers must also be sterilized.
Injectable suspensions may also be prepared, in which case
appropriate liquid carriers, suspending agents and the like may be
employed.
[0049] The invention will now be described with reference to the
accompanying examples which should not be construed to limit the
scope of the invention:
EXAMPLES
Example 1
[0050] A blend of Symplocos racemosa, Woodfordia fruticosa, and
Mangifera indica was coarsely powdered and extractions were carried
out as per the following procedures.
[0051] (a) The coarse powder was extracted with water in a steam
jacketed boiling pan for 3 hours and the decoction was filtered
through 100 mesh nylon cloth and collected the filtrate. The herbs
were again extracted with water for another 3 hours and the
filtrate was collected as earlier. The total filtrate was
concentrated in steam jacketed boiling pan until viscous mass was
formed. This semisolid mass was dried in hot air oven at
70-75.degree. C. until the moisture content was brought down to
below 5%w/w. The dried extract was analyzed for crude flavonoid
content by an established method.
[0052] (b) The coarse powder of the above herbs was extracted with
75% alcohol in a Soxhlet apparatus for about 6 hours. The extract
obtained was concentrated in a Buchi Rotavapour and finally dried
in oven. The dried extract was analyzed for flavonoid content.
3 Flavonoid content Aqueous extract 1.89% w/w Hydro alcoholic
extract 7.34% w/w
Example 2
[0053] Saraca indica, Emblica officinalis, Terminalia chebula,
Terminalia belerica, Zingiber officinale, Cyperus rotundus,
Pterocarpous santalimus, Beriberis aristata, Cuminum cyminum,
Adhatoda vasika, Nelumba nucifera and Piper longum were mixed and
coarsely powdered in Retsch cutting mill using 10 mesh sieve and
extracted with water as per the procedure mentioned in example
1(a).
[0054] Preparation of Samples for Studies+
[0055] Sample A: The resultant extract was mixed with the aqueous
extract of the example 1(a).
[0056] Sample B: The resultant extract was mixed with the hydro
alcoholic extract of the example 1(b)
[0057] The above two samples were assayed for their effect on
Uterotonic activity using Wistar female albino rats.
[0058] Materials:
[0059] 1.Stilbestrol dipropionate, 5-hydroxytryptamine creatinine
sulphate (5-HT), De Jalon's solution, Extracts of Sample A &
Sample B
[0060] 2. Wistar albino rats
[0061] Methods:
[0062] The uterotonic property of the test extracts were assessed
in two test areas.
[0063] 1. The oxytocic activity of the Sample A and Sample B is
compared with uterine stimulant 5-HT.
[0064] Female rats weighing between 150-200 g were pre-treated with
stilbestrol dipropionate, 1 mg/kg intra peritoneally 24 h prior to
the experiment. The rats were killed by a swift blow on the head
and exsanguinated. The uterus of rat dissected and the two horns
divided. One horn is suspended in the bath. The rhythmic
contractions are abolished by using de jalon's solution. When the
spontaneous contractions became regular, the responses to Extracts
of Sample A and Sample B and other agonists were recorded using a
Frontal lever, isometrically connected to a polygraph.
[0065] 2. Subsequently, the oxytocic activity of the Sample A is
also compared with Sample B on uteri isolated from rats pre-treated
with the extracts for duration up to 3 weeks.
[0066] Rats were fed orally test extracts daily for 3 weeks before
sacrifice and the uterus treated as above.
4 Effect of pre- treatment on in- Samples In-vitro treatment vitro
study Samples + 5-HT 5-HT Uterine contraction Increased contraction
Sample A No Uterine Contraction Potentiation effect contraction
Sample B No Uterine Increased Potentiation effect contraction
contraction The results of the above experiments are summarized
hereunder. 1. The control drug 5-HT induced a dose related increase
in the height of contraction of rat isolated uterus. 2. There was
no response with Sample A or Sample B on the uterus isolated from
stillbestrol treated rats. 3. Pre-treatment with test samples
orally for 3 weeks produced significant contractile effect as
compared to the control drug 5-HT. 4. Sample B was found to be most
active as it has shown the maximum height of contraction at the
similar dose level.
[0067] Both the test samples used in the study failed to invoke
uterotonic activity per se when used in stilbestrol primed rats.
However, a pre-treatment with the test samples was found to invoke
uterotonic activity; of those, sample B was found to exert a
stronger effect superceding sample A.
Example 3
[0068] Preparation of Plant Coagulate:
[0069] Spinach (Spinacia oleracea) and Berseem (Trifolium
alaxandranum) leaves were washed in water and then pulped
separately in a chopper mill and the resultant mass was expressed
to get the juice. The collected juice of Spinach and Berseem was
mixed in the ratio of 1:3 respectively. The juice was heated in a
boiling pan at 80-85.degree. C. After completion of the coagulation
process, coagulate was collected by filtration. Finally dried in an
oven to get the combined plant coagulate.
Example 4
[0070] The herbal extract of Example 2(b) enriched with combined
plant coagulate obtained in Example 3 and herbal extract of Example
2(a) were formulated into hard gelatine capsule dosage form and
their efficacy had been compared by a clinical study.
5 Formulation I Sl.No. Ingredients % w/w 1. Herbal extract of 2(b)
35-55 2. Combined Plant coagulate 45-65 3. Excipients q.s.
Ingredients 1, 2 & 3 were sifted through #30 sieve and mixed
properly in Kenwood mixer for 15 minutes. Then the powder blend was
filled in '0' size capsules using capsule filling machine.
[0071]
6 Formulation II Sl.No. Ingredients % w/w 1. Herbal extract of 2(a)
35-55 2. Excipients q.s. The powder blend was filled in '0' size
capsules.
[0072] Ten patients suffering from dysfunctional uterine bleeding
and associated anemia in the same age group were enrolled. The
patients were separated in to two groups consisting of 3
menorrhagia and 2 polymenorrhea patients. Group I received
Formulation I and the other group received formulation II for 3
months at the dose of one capsule twice daily. Both the
formulations showed activity against dysfunctional uterine
bleeding, but Group I showed better activity than Group II. The
patients who received Formulation I showed an increase in
hemoglobin content from 8.24.+-.0.5g/dl to 12.21.+-.0.38 g/dl where
as the patients who received formulation II showed no increase in
hemoglobin content.
7 Dry weight Blood loss of pads Patient grading No. of pads Before
After No. Formulation Diagnosis B A B A g g 1 I Menorrhagia 5 0 31
17 1550 650 2 I Menorrhagia 4 0 32 15 1600 750 3 I Menorrhagia 3 0
31 14 1550 600 4 I Polymenorrhoea 3 0 22 13 1200 750 5 I
Polymenorrhoea 4 0 24 13 1550 550 28 .+-. 4.15 14.4 .+-. 1.5 1490
.+-. 146.29 660 .+-. 80 6 II Menorrhagia 4 0 36 18 1300 800 7 II
Menorrhagia 4 0 26 15 1750 850 8 II Menorrhagia 3 0 23 15 1150 750
9 II Polymenorrhoea 2 0 31 17 1550 700 10 II Polymenorrhoea 2 0 25
14 1500 750 28.2 .+-. 4.7 15.8 .+-. 1 47 1450 .+-. 207.36 770 .+-.
50.1
[0073]
8 B-Before treatment A-After treatment Hemoglobin content Patient
g/dl No. Group Diagnosis B A 1 I Menorrhagia 7.5 11.5 2 I
Menorrhagia 8.2 12.0 3 I Menorrhagia 8.5 12.6 4 I Polymenorrhoea
9.0 12.5 5 I Polymenorrhoea 8.0 12.2 8.24 .+-. 0.5 12.16 .+-. 0.39
6 II Menorrhagia 7.5 8.7 7 II Menorrhagia 8.5 9.0 8 II Menorrhagia
8.5 9.0 9 II Polymenorrhoea 9.0 9.0 10 II Polymenorrhoea 9.0 9.0
8.5 .+-. 0.55 8.94 .+-. 0.12
[0074]
9 Duration of bleeding was also measured. Patient Duration(no.of
days) No. Group Diagnosis B A 1 I Menorrhagia 12 4 2 I Menorrhagia
6 3 3 I Menorrhagia 7 4 8.33 .+-. 2.62 3.66 .+-. 0.47 6 II
Menorrhagia 6 4 7 II Menorrhagia 7 4 8 II Menorrhagia 7 4 6.66 .+-.
0.47 4
[0075] Since many apparently different embodiments of the present
invention could be made without departing from the spirit and scope
thereof, it is intended that the description of the invention
herein be interpreted as being illustrative only and not limiting
in any manner whatsoever.
* * * * *