The present invention relates to a poly herbal formulation for Pre-menstrual syndrome. More
5 particularly, the present invention relates to an oral polyherbal fixed dose formulation for premenstrual syndrome and process thereof for relaxation of the muscles during menstruation
and for increasing the blood circulation to uterine wall and comfort during menstruation. The
present invention is helpful in relief from cramps or pain associated during menstruation
mainly for Primary dysmenorrhea and pre-menstrual syndromes. The polyherbal fixed dose
10 formulation is effective for irregular menstrual cycle resulting from the synergy of this
composition.
BACKGROUND OF THE INVENTION:
Premenstrual Syndrome (PMS) is a disorder that causes physical and emotion symptoms.
15 It affects women 1 to 2 weeks before their period. PMS can cause mood swings, headache,
and bloating. Medicine, therapy, and healthy habits can help ease symptoms.
PMS encompasses a vast array of psychological symptoms such as depression, anxiety,
irritability, loss of confidence and mood swings. There are also physical symptoms, typically
20 bloatedness and mastalgia. It is the timing, rather than the types of symptoms, and the
degree of impact on daily activity that supports a diagnosis of PMS. The character of
symptoms in an individual patient does not influence the diagnosis. In order to differentiate
physiological menstrual symptoms from PMS, it must be demonstrated that symptoms
cause significant impairment to the individual during the luteal phase of the menstrual cycle.
25 Premenstrual syndrome (PMS) is a combination of emotional, physical, and psychological
disturbances that occur after a woman's ovulation, typically ending with the onset of
her menstrual flow. The most common mood-related symptoms are irritability, depression,
crying, oversensitivity, and mood swings.
30 Pre-menstrual syndrome (PMS) is a well-known condition that occurs in many women
throughout the world. PMS typically involves menstrual cramps, emotional stress and
2
agitation, bloating, and an abnormal amount of menstrual discharge in women for an
abnormal duration of time. PMS varies from mild discomfort and emotional problems to
complete physical disability. PMS is thought to result from a complex interplay of hormone,
imbalance, nutritional deficiencies, and psychological factors. Possible theories of the cause
5 of PMS include a vitamin B6 deficiency, hypoglycemia, hormonal allergy, or a psychosomatic
problem.
The menstrual cycle is a unique physiological event in the reproductive system of female
Mammals which makes pregnancy possible. The first menstrual cycle (menarche) usually
occurs between12 to 15 year of age; these cycles end around the of age of 50 years, i.e. at
10 Menopause. The menstrual cycle is calculated as the duration from the first day of bleeding
to the beginning of the next bleed. Although a menstrual cycle is 28 days on average, it
could be a little shorter or longer. In general, a normal menstrual cycle usually lasts between
21 and 35 days.
15 Almost every woman suffers from PMS at one time or another in her reproductive lifetime. It
is estimated that over sixty-seven percent of all women experience significant symptoms of
PMS for which they seek some type of intervention. It is further estimated that over thirtythree percent of all women have had medical treatment for PMS sometime in their lives.
The multiple remedies available to treat PMS simply do not offer relief from that condition.
20 PMS has been the reported cause of discomfort leading to loss of work or school in many
women, and has been listed as a significant problem in the offices of a great many
gynecologists. It is thought that some women have PMS at various times in their lives as a
result of a combination of events or conditions.
25 Most women manage their symptoms of primary dysmenorrhea, with primarily over the
counter (OTC) pain medications (e.g. ibuprofen and paracetamol/acetaminophen), and selfcare including rest and the application of heat, rather than seeking medical advice. Lack of
satisfactory pain relief and effective medical interventions in primary dysmenorrhea leads to
an uptake of self-care strategies by women. Complementary, non-pharmacological or
30 traditional medicine usage (such as herbal medicines or dietary changes) are often a
significant component of self-care
3
The use of herbs and plants to treat ailments and generally improve overall health has
become common place. Many natural remedies are available for PMS such as Meditation,
Aromatherapy, warm bath, exercise, through different menstrual products such as Menstrual
cups, yoga, sleep, diet, acupuncture, and supplements such as calcium; magnesium;
5 vitamin E and vitamin B6. Several herbal remedies are mentioned in the prior art such as
primrose oil, chaste berry, gingko and St. John’s wort.
One of the prior art means discloses a “Herbal composition for promoting hormonal
balance in women and methods of using same” in patent application no. US 6242012. It
contains supercritical extracts of ginger, rosemary and evening primrose oil, and either
10 regular or supercritical (preferably regular) extracts of black cohosh, dong quai, schizandra
berry, chaste tree berry and rosemary
Another one prior art means is disclosed in “Ayurvedic/ herbal dry syrup formulation for
pre-menstrual syndrome and uterine disorders” disclosed in patent application no. IN
1334/DEL/2011. The dry herbal syrup formulation comprises herbal extract of Ashoka
15 (Saraca indica), Lodra (Symplocus racemosa), Satavar (Asparagus racemosus), Nagkesar
(Mesua ferra), vasa (Adhatoda vasaka), Kasni (Chicorium intybus), Jatamansi
(Nardostachysjatamansi), Aswagandha (Withania somniferd), Tulsi (Ocimum sanctum),
Shilajeet (Asphaltum), Amla {Emblica officinalis), Harad (Terminalia chebula), Baheda
(Terminalia balerica).
20
Another one prior art means is disclosed in a PMS Relief - Organic Botanical Hormonal
Balance Extract Supplement for Women under the brand name “High drops”. 100% PLANTBASED: 7 powerful herbs that are organic, ethically wild harvested, and / or selectively
imported: Wild Yam Root, Dong Quai Root, Chaste Tree Berry, Black Cohosh Root, Milk
25 Thistle Seed, and Motherwort Herb. Scientifically proven to provide effective PMS PMDD
symptom relief. Developed by a clinical herbalist for maximum efficacy, potency, and
stability.
4
The prior art means used for premenstrual; syndrome causes adverse side effects. Until
now there has been no single method is developed to effectively combat these symptoms.
Thus far, no conventional form of intervention has been proven to show significant success
in ameliorating PMS.
5
Thus, there is a need to provide an oral polyherbal fixed dose formulation for pre-menstrual
syndrome. The present invention is having an improved therapeutic efficacy without the
adverse toxic effects associated with conventional modes of treatment. The present
invention provides an oral polyherbal fixed dose formulation which reduces anxiety and
10 breast tenderness and helps in easing irritability and helps to relieve mood swings.
OBJECTS OF THE INVENTION:
The main object of the present invention is to provide an oral polyherbal fixed dose
formulation for pre-menstrual syndrome
15
Another object of the present invention is to provide cost effective solution which provide an
anti-infective, astringent, anti-inflammatory, antispasmodic, diuretic actions with
supplementation of micro-nutrients.
20 Yet another object of the present invention is to provide an oral polyherbal fixed dose
formulation which reduces anxiety and breast tenderness and helps in easing irritability and
helps to relieve mood swings.
Yet another object of the present invention is to help in relieving dysmenorrhea associated
25 symptoms like anxiety and lack of energy.
SUMMARY OF THE INVENTION:
Accordingly, an oral polyherbal fixed dose formulation for pre-menstrual syndrome and
process thereof for pre- menstrual syndrome especially for relaxation of the muscles during
30 menstruation is disclosed. The present invention helps in reduces anxiety and breast
tenderness and helps in easing irritability and helps to relieve mood swings. The oral
5
polyherbal fixed dose formulation of the present invention provides an anti-infective,
astringent, anti-inflammatory, antispasmodic, diuretic actions with supplementation of micronutrients and reduces anxiety and breast tenderness. The oral polyherbal fixed dose
formulation for pre-menstrual syndrome comprising of; active ingredients like 75 mg of
5 Chamomile flower; 100 mg of Chaste berry fruit extract; 75 mg of Fenugreek seed extract;
75 mg of Ginger juice powder; 5 mg of Black cohosh root extract; 200 mg of Myo-inositol;
150mcg of Vitamin B1; and 200mcg of Vitamin B6 respectively and excipients (binding
agent).
10 DESCRIPTION OF THE DRAWINGS:
Fig 1 depicts the graph for baseline in quality of life-health status.
Fig 2 shows total means score ACOG – PMS questionnaire.
Fig 3 depicts menstrual pain intensity-VAS score.
Fig 4 shows the time taken for pre-menstrual syndrome.
15 Fig 5 shows daywise time taken for pre-menstrual syndrome.
Fig 6 shows graph showing change from baseline upto day 5 in ESR level.
Fig 7 shows graph showing change from baseline upto day 5 in Hs CRP level.
Fig 8 depicts graph showing change from baseline upto day 5 in PGF2α level.
Fig 9 shows graph showing change from baseline upto day 5 in serum fibrinogen level.
20 .
DETAILED DESCRIPTION OF THE INVENTION WITH REFERENCE TO
DRAWINGS:
The invention will now be described in detail in connection with certain preferred and optional
embodiments, so that various aspects thereof may be more fully understood and
25 appreciated.
The present invention relates to an oral polyherbal fixed dose formulation for pre-menstrual
syndrome and process thereof for relaxation of the muscles during menstruation. The
present invention is for pre-menstrual syndrome and uterine disorders in the form such as
30 but not limited to granules or powder with flavored base that is easily dispersible in potable
6
water medium before use. The oral polyherbal fixed dose formulation of the present
invention is chemically and microbiologically stable during consumption.
The oral polyherbal fixed dose formulation of the present invention is cost effective and used
5 for treating different health problems related to pre-menstrual syndrome and uterine
disorders. The herbal extracts used in this formulation provide an anti-infective, astringent,
anti-inflammatory, antispasmodic, diuretic actions with supplementation of micro-nutrients.
The oral polyherbal fixed dose formulation of the present invention reduces anxiety and
breast tenderness. The oral polyherbal fixed dose formulation of the present invention also
10 helps in easing irritability. The polyherbal formulation of the present invention helps to relieve
mood swings. The oral polyherbal fixed dose formulation of the present invention is with all
the natural ingredients enriched with vitamins B1 and B6. The oral polyherbal fixed dose
formulation of the present invention is suitable for vegetarians and vegans. The oral
polyherbal fixed dose formulation of the present invention helps bloating through menstrual
15 period and relieves dysmenorrhea associated symptoms like anxiety and lack of energy.
In a Preferred embodiment of the present invention, an oral poly herbal fixed dose
formulation for pre-menstrual syndrome and uterine disorders comprising of herbal extract
of Chamomile flower extract; Chasteberry fruit extract; Fenugreek seed extract; Ginger juice
20 powder; Black cohosh root extract; Myo-inositol; Vitamin B1 and Vitamin B6 is provided.
Chamomile flower (Matricaria Recutita) is more commonly known as German Chamomile
or simply Chamomile, and is a member of the Aster family of plants. Matricaria
Chamomilla is a member of the Asteraceae family, commonly referred to as the daisy family.
25 Chamomile is used as a traditional medicine for its anti-inflammatory, antibacterial,
astringent, and general healing abilities.
The primary bioactive ingredients of Chamomile Flower Extract are favanoids, terpenoids,
coumarins and polyacetylenes. The plant's healing properties come from its daisy-like
flowers, which contain volatile oils (including bisabolol, bisabolol oxides A and B, and
30 matricin) as well as flavonoids (particularly a compound called apigenin) and other
therapeutic substances.
7
Chasteberry fruit extract (Vitex Agnus-Castus) is the name of the largest genus in
the Verbenaceae plant family, includes 250 species worldwide. Vitex agnus-castus tree is a
shrub that is native to the Mediterranean and Central Asia. The shrub has long, finger-shaped
5 leaves, blue-violet flowers, and dark purple berries. The fruit and seed are used to make
medicine. The Vitex agnus-castus fruit, also known as chasteberry or monk’s pepper, is
about the size of a peppercorn. This fruit — as well as other parts of the plant — are typically
used as an herbal remedy to treat a variety of ailments. It is used to treat symptoms of
menopause, and other conditions affecting a woman’s reproductive system.
10
Fenugreek (Trigonella foenum-graecum) is an herb long used in alternative medicine. It’s
a common ingredient in Indian dishes and often taken as a supplement. Fenugreek is a plant
that stands around 2–3 feet (60–90 cm) tall. It has green leaves, small white flowers, and
pods that contain small, golden-brown seeds. Fenugreek has been used appetite control
15 and Inflammation. Fenugreek has effective for Painful menstrual periods (dysmenorrhea).
Ginger (Zingiber officinale) is a flowering plant that originated in Southeast Asia. It belongs
to the Zingiberaceae family. The rhizome (underground part of the stem) is the part
commonly used as a spice. It’s often called ginger root or, simply, ginger. Ginger can be
used fresh, dried, powdered, or as an oil or juice. It’s a very common ingredient in recipes.
20 It’s sometimes added to processed foods and cosmetics. Ginger significantly reduces the
levels of TNF- alpha, IL-6 and CRP. Anti-inflammatory effects of Zingiber officinale are
attributed to its Gingerols.
Black cohosh (Actaea racemose) is an herb. The root is used for medicinal purposes.
The root of black cohosh is used for medicinal purposes. Black cohosh root contains
25 several chemicals that might have effects in the body. Some of these chemicals work on
the immune system and might affect the body’s defenses against diseases. Some might
help the body to reduce inflammation. Other chemicals in black cohosh root might work in
nerves and in the brain. These chemicals might work similar to another chemical in the
brain called serotonin. This type of chemical is called a neurotransmitter because it helps
8
the brain to send messages to other parts of the body.
Black cohosh root also seems to have some effects similar to the female hormone,
estrogen. In some parts of the body, black cohosh might increase the effects of estrogen.
5 In other parts of the body, black cohosh might decrease the effects of estrogen. Estrogen
itself has various effects in different parts of the body. Estrogen also has different effects in
people at different stages of life. Black cohosh acts as an herb that acts similar to estrogen
in some people.
10 In preferred embodiment of the present invention, an Oral Polyherbal fixed dose formulation
is disclosed. An oral polyherbal fixed dose formulation comprising of;
a. 75mg of Chamomile flower ext.;
b. 100mg of Chaste berry fruit ext.;
c. 75mg of Fenugreek seed ext.;
15 d. 75mg of Ginger juice powder;
e. 5mg of Black cohosh root ext.;
f. 200mg of Myo-inositol;
g. 150mcg of Vitamin B1; and
h. 200mcg of Vitamin B6.
20
In another embodiment, an oral polyherbal fixed dose formulation is formed through a
process; wherein the Process for synthesis of oral polyherbal fixed dose formulation
comprising the steps of;
a. Drying the plant parts of each herb and preparing the dried powder of each herb and
25 Myo-Inositol, Microcrystalline cellulose, Lactose DC anhydrous by passing through
40 mesh sized sieve followed by collection of dried powder of herbs in double line
polybag;
b. Loading all the ingredients in rapid mixer granulator (RMG) followed by Starting
impeller at slow speed with chopper off followed by mixing for 10 minutes;
30 c. Mixing the sieved powders of all extracts in a predetermined ratio in a mixer to
uniform mixing;
9
d. Granulating the herbal extract dry mixture in RMG by gradually adding binding
agent at slow/fast impeller speed and chopper off/on at slow/fast speed followed
by addition of Isopropyl Alcohol & Water mixture if required to achieve desired
granules;
5 e. Loading the wet mass in Fluidized bed dryer(FBD) followed by air drying the
granules for a period of 5 to 10 min after heat drying the granules at a temperature
at 500C±50C to obtain desired Loss on drying(LOD);
f. Compressing Size of the dried granules through mesh 18 sieve using vibratory sifter
and collecting it in double polybags followed by Sizing the oversize granules using
10 Multi-mill through 1.5mm screen and again pass through mesh 18 sieve and collect
in double line polybags;
g. Sifting all the dispensed materials through mesh 40 sieve & collecting it in double
line polybags followed by blending of the Load granules and Lubricants in Octagonal
Blender for 10 minutes followed by Unloading the material in double line polybags;
15 h. Carrying out film coating of the tablets followed by packaging.
Yet in another embodiment, The oral polyherbal fixed dose formulation of the present
invention comprises a mixture of active substances; Chamomile flower; Chasteberry fruit
extract; Fenugreek seed extract; Ginger juice powder; Black cohosh root extract; and myoinositol and excipients (binding agents).
20 In another embodiment, binding agents are selected from the group of isopropyl alcohol,
hydroxypropyl cellulose (HPC); xylitol, gelatin; polyvinyl pyrrolidone (PVP), polyethylene
glycol (PEG); water or alcohol; methyl cellulose, polyvinylpyrrolidone and polyethylene
glycol sucrose, lactose; starches, cellulose; natural gum.
In preferred embodiment of the present invention, the excipients (binding agent) is preferably
25 Isopropyl alcohol and Polyvinyl Pyrrolidone (PVP).
In a preferred embodiment of the present invention, isopropyl alcohol is used as a binding
agent. 900ml of Isopropyl Alcohol-IP is taken in a suitable stainless steel container followed
by addition of 100 ml of water IP in it under continuous stirring. Taking above binder
10
solution in a suitable stainless steel container followed by adding 73.50 gm of Polyvinyl
Pyrrolidone (K-30) IP under continuous stirring with stirrer (till it swells completely).
Additional Isopropyl Alcohol & Water mixture can be added carefully to achieve desired
granules if required.
5 In another embodiment, dispensed materials include Crospovidone IP(XL-10), Talc IP,
Sodium Starch Glycolate IP, & Vitamin B1 (Thiamin Mononitrate) & Vitamin B6 (Pyridoxine
hydrochloride) respectively.
In another embodiment of the present invention, film Coating Solution is prepared for coating
the tablets in which IPA (isopropyl alcohol) is taken in SS Vessel equipped with mechanical
10 stirrer followed by addition of Instacoat universal IC-U-2959 (Transparent) slowly in it & mix
it for 10min followed by addition of MDC (Methylene dichloride) into solution with continual
stirring for a period of 30 min followed by filtration of the solution through mesh 100 sieve
and is used for coating. The tablet is coated in Coating Pan till 2% coating is achieved.
15 In another embodiment, Chamomile flower extract of the polyherbal fixed dose formulation
for pre-menstrual syndrome is in concentration range of 70- 75 mg. Chasteberry fruit extract
of the polyherbal fixed dose formulation for pre-menstrual syndrome is in concentration
range of 90-100 mg. Fenugreek seed extract of the polyherbal fixed dose formulation for
pre-menstrual syndrome is in concentration range of 65-75 mg. Ginger juice powder of the
20 polyherbal fixed dose formulation for pre-menstrual syndrome is in concentration range of
65- 75 mg. Black cohosh root extract of the polyherbal fixed dose formulation for premenstrual syndrome is in concentration range of 2- 5 mg. Myo-inositol of the polyherbal
fixed dose formulation for pre-menstrual syndrome is in concentration range of 120-150 mg.
Vitamin B1 of the polyherbal fixed dose formulation for pre-menstrual syndrome is in
25 concentration range of 120- 150mcg. Vitamin B6 of the polyherbal fixed dose formulation for
pre-menstrual syndrome is in concentration range of 170-200mcg.
Chamomile has anti-anxiety and mood relieving effect by acting on CNS due to presence of
flavonoid (Apigenin) and phytoestrogen type substance. Vitus agnus castus (chasteberry
30 fruit) helps in significant improvement in symptoms like breast fullness by reducing the
prolactin level which increases by stress. Fenugreek contains diaosgenin named saponins
11
which acts as cortisone and consequently reduces anxiety. Ginger inhibits prostaglandin
synthesis thereby reducing hyper contractility of uterus. Black cohosh reduces the
vasomotor symptoms like palpitation and irritability. Myo-inositol reduces the symptoms of
pre-menstrual dysphoric disorder, by working on serotonergic systems increasing
5 tryptophan transport. Pyridoxine affects brain monoamine metabolism specifically by an
alteration in the metabolism of tryptophan thereby reduces depression. Vitamin B1 increases
endorphin secretion and subsequently causes relaxation and stimulates sleep through
affecting the brain and liver releasing ATP. It also promotes cardiovascular system
functioning.
10 Experimental data:
The present study has been planned to study the efficacy and safety of an oral polyherbal
formulation of the present invention. Ninety female participants divided into 3 arms of 30 in
each arm. A total of 90 female study participants who are clinically diagnosed to have
15 primary dysmenorrhea were included in the study. The selection of the patients were based
on initial screening and study criteria. Initial screening comprised of baseline investigations
mentioned below.
1. Complete blood count – includes hemoglobin, RBC count, WBC total & differential count,
platelet count, peripheral blood smear, ESR, Serum fibrinogen
20 2. Urine routine.
3. Biochemical parameters – Random blood sugar, CRP, Urea, Creatinine, Bilirubin, AST &
ALT(LFT).
4. Microbiological parameter- HIV and HBsAg.
5. Previous Ultrasonogram (USG) abdomen and pelvis reports (for diagnosing PCOS and
25 Fibroid). If patients had old reports (within 6 months duration), it was not repeated. All the
above tests were done during baseline screening. Demographic data including name, sex,
age, body weight (Kg) and height (m) in terms of BMI, body build, tobacco use and medical
and menstrual histories of participants were recorded. Each subject will undergo thorough
general and systemic examination.
30 Inclusion criteria:
12
1. Female participants between the age of 18-50 years (both inclusive) with regular/irregular
menstrual cycles who are clinically diagnosed to have primary dysmenorrhea.
2. Subjects with stable vitals like pulse and blood pressure
3. Patient should have not participated in any other clinical trial during the past 3 months.
5 4. Participants who are willing to give written, signed and dated informed consent to
participate in the study.
Exclusion Criteria:
1. Secondary dysmenorrhea
2. History of presence of any other Gynecological diseases.
10 3. Pregnant or breastfeeding or planning to become pregnant during the study period.
4. Known case of Hypersensitivity to any of the Investigational drug content.
5. Patients suffering from abnormal hematological or biochemical (renal & liver function)
blood parameters.
6. Received any other investigational medicine within 7 days prior to screening which can
15 interfere with investigational product activity.
7. Suffering from any illness which will interfere with present study as decided by clinical
investigator.
The preferred dose of the film coated (premenstrual syndrome)tablets of the present
20 invention is one tablet thrice daily orally 3 days before menses in both arm 1 & 2.
Participants were randomized into 3 groups (2 test and 1 comparator product) with 30 in
each group.
Group 1- Participants with Primary dysmenorrhea took one tablet of premenstrual syndrome
tablet orally thrice daily 3 days before menses. All the study participants who satisfy the
25 study criteria were included in the study. They underwent standard treatment appropriate to
their illness as per the standard management guidelines.
The study protocol, CRFs, regulatory clearance documents, product related information and
informed consent form (in English & Tamil) were submitted to the Human Ethics Committee
for approval by the same. Only after obtaining a proper Informed consent from the study
30 participants, the study commenced according to the study protocol.
Evaluation Criteria
13
The primary outcome measures to study the efficacy are as follows:
1. Change from baseline in menstrual pain intensity measured by Pain VAS Scale (0-
10)
Time Frame: Day 0- Day 5
5 Testing Interval: Day 0, Day 3, Day 5
2. Changes from base line in following laboratory parameter(s):
• Prostaglandin (PGF2α) – Directly proportional marker for etiology of Primary
Dysmenorrhea
• Hs-C Reactive Protein
10 • ESR
• Serum fibrinogen
• Complete Blood Count
• Renal Function Tests
• Liver Function Tests
15 Time Frame: Day 0- Day 5
Testing Interval: Day 0, Day 5
3. Duration for pain relief in hours (After medication)
Time Frame: Day 0- Day 5
Testing Interval: Day 0, Day 3, Day 5(Through Patient diary)
20 4. Changes from base line in Quality of life- Questionnaires (Short Form Health-12).
Time Frame: Day 0- Day 5
Testing Interval: Day 0, Day 5
5. Change in the Pre-menstrual syndrome assessment questionnaire (ACOG PMS
Questionnaire) and compare it with other group (arm 3)
25 Time Frame: Day 0- Day 5
Testing Interval: Day 0, Day 5
The secondary outcome measures to assess the safety and tolerability of the study drugs
by monitoring any adverse events during the study period using clinical and laboratory
Evaluation.
30 Safety and tolerability evaluation criteria:
• Adverse events and serious adverse events during the study period
14
• Laboratory (haematology and biochemistry) parameters (if any)
• Brief clinical examination
• Vital signs (pulse rate, respiratory rate, systolic and diastolic blood pressure, and
body temperature)
5 Time Frame: Day 0- Day 5
Testing Interval: Day 0, Day 5
A statistically significant improvement (using SPSS software version 23.0) in the clinical
parameters along with the study specific efficacy parameters at the end of the study will
prove the efficacy and safety of oral polyherbal fixed dose formulation in the management
10 of Primary Dysmenorrhea and Premenstrual Syndrome.
Participant monitoring
Participants were monitored throughout the study. The basic hematological and biochemical
parameters were checked on screening and at the end of the study. Any adverse reactions
due to the study formulations and/or study procedures were recorded and reported as per
15 the latest regulatory guidelines.
The results are as follows:
Table 1 shows changes from base line in quality of life –questionnaires. There is no
significant abnormalities detected post intervention, in any other laboratory parameters like
20 pathological and biochemical investigations. There is no renal or hepatotoxicity with respect
to any of the test drugs involved in the study.
15
16
Table 1
-P value <0.05. There is a significant improvement in the mean percentage scores of quality
of life-questionnaires after treatment on day 5, which is more evident in group 1 and 2. There
5 is a significant improvement in the overall health status as very good and excellent in group
1 with 57% and group 2 with 52% participants when compared to group 3 with 40% of
participants.
There is also a significant improvement in the overall physical activity status with no
limitations in group 1 with 83% and group 2 with 83% participants when compared to group
10 3 with 66% of participants.
Table 2 shows change in the pre-menstrual syndrome assessment questionnaire –Mean
scores before and after treatment (ACOGPMS questionnaire).
17
18
Table 2
-P value<0.001. There is a significant improvement in the means cores of pre-menstrual
syndrome assessment questionnaire after treatment in group 1 and group 3, both at the
5 baseline and at the end of the treatment. There is a good improvement in the premenstrual
(psychological aspect) symptoms like anxiety,irritability and mood swings in group 1 & 2
compared to group 3 and also with respect to premenstrual (physical aspect) symptoms like
headche,fatigue, and dizziness there is a good improvement in group 1 and 2 compared to
group 3.
10
Table 3 shows Change from baseline up to Day 5 in menstrual pain intensity measured
by Pain VAS Scale:
Table 3
15
There is a significant reduction in the VAS score in all the three groups after treatment on
day 3 and 5. It is more evident in group 1 and 2 on day 5.
Table 4 shows change in duration (time taken) for pain relief (menstrual pain) from baseline
20 up to Day 5 in minutes
19
Table 4
On day 5: The time taken for onset of pain relief was early at around 6 minutes in group 2
5 followed by group 1 with 7.5 minutes and group 3 with 9 minutes.
On day 3: The time taken for onset of pain relief was early at around 45 minutes in group 3
Followed by group 1 with 50 minutes and group 2 with 54 minutes.
On day 0: The time taken for onset of pain relief was early at around 124 minutes in group
3 followed by group 1 with 127 minutes and group 2 with 140 minutes.
10 Table 5 shows change from base line up to day 5 in the inflammatory marker (ESR):
Table 5
15
20
There is a significant reduction in ESR levels in all the three groups on day 5 compared to
day 0. Table 6 shows change from base line up to day 5 in the inflammatory marker (Hs
CRP).
5
Table 6
There is a significant improvement (reduction) in the Hs CRP levels on day 5 compared to
day 0, which is more evident in group 1 followed by group 3 & 2 respectively.
10 Table 7 shows change from base line upto day 5 in the inflammatory marker (PGF2α).
21
Table 7
There is a significant improvement (reduction), in the PGF2α levels in all the three groups
on day 5 compared to day 0.
5 Table 8 shows change from base line upto day 5 in the inflammatory marker (Serum
Fibrinogen).
Table 8
10
There is a significant improvement (reduction), in the serum fibrinogen levels, on day 5
compared to day 0, which is more evident in group 1 followed by group 3 & 2 respectively.
Table 9 shows other blood parameters of different groups on day 0 and day 5.
15
22
Table 9
Table 10 shows change in the pre-menstrual syndrome questionanire- total mean scores
5 before and after treatment (ACOG:PMS questionnaire).
Table 10
P value<0.001. There is a highly significant improvement in the total means scores of pre10 menstrual syndrome assessment questionnaire after treatment in group 1 and group 2. The
pre-menstrual symptoms have come down in group 1 and 2 on treatment with premenstrual
syndrome tablet which is not evident meftal spas treated group.
Observations:
15
From this study, it is evident that oral fixed dose polyherbal formulation is effective and safe
for premenstrual syndrome and primary dysmenorrhea disorders. It has shown a very quick
23
onset of action and reduction in menstrual pain, on day 0 and better than all other prior art
products (Meftal spas) on day 5.
The oral fixed dose polyherbal formulation of the present invention gives better pain relief in
5 primary dysmenorrhea, better improvement of inflammatory markers, simple dose
determination, and are easy for patients to use. It also lowers the risk of systemic adverse
events, drug-drug interactions and thus provides a good patient compliance. So in terms of
efficacy and adverse effects, this tablet is superior as compared to other conventional routes
for treatment.

We claim:
1) An oral polyherbal fixed dose formulation for pre-menstrual syndrome; with active
ingredients and excipients (binding agents); comprising of;
a. 75 mg of Chamomile flower;
5 b. 100 mg of Chasteberry fruit extract;
c. 75 mg of Fenugreek seed extract;
d. 75 mg of Ginger juice powder;
e. 5 mg of Black cohosh root extract;
f. 200 mg of Myo-inositol;
10 g. 150mcg of Vitamin B1; and
h. 200mcg of Vitamin B6.
2) The polyherbal fixed dose formulation for pre-menstrual syndrome as claimed in claim 1,
wherein the said Chamomile flower extract is in concentration range of 70- 75 mg.
15 3) The polyherbal fixed dose formulation for pre-menstrual syndrome as claimed in claim 1,
wherein the said Chasteberry fruit extract is in concentration range of 90-100 mg.
4) The polyherbal fixed dose formulation for pre-menstrual syndrome as claimed in claim 1,
wherein the said Fenugreek seed extract is in concentration range of 65-75 mg.
20
5) The polyherbal fixed dose formulation for pre-menstrual syndrome as claimed in claim 1,
wherein the said Ginger juice powder is in concentration range of 65- 75 mg.
6) The polyherbal fixed dose formulation for pre-menstrual syndrome as claimed in claim 1,
25 wherein the said Black cohosh root extract is in concentration range of 2- 5 mg.
7) The polyherbal fixed dose formulation for pre-menstrual syndrome as claimed in claim 1,
wherein the said Myo-inositol is in concentration range of 120-150 mg.
30 8) The polyherbal fixed dose formulation for pre-menstrual syndrome as claimed in claim 1,
wherein the said Vitamin B1 is in concentration range of 120- 150mcg.
25
9) The polyherbal fixed dose formulation for pre-menstrual syndrome as claimed in claim 1,
wherein the said Vitamin B6 is in concentration range of 170-200mcg.
5 10) The oral polyherbal fixed dose formulation for pre-menstrual syndrome as claimed in
claim 1, wherein the said oral polyherbal dosage formulation is prepared by a process
comprising the steps of;
a. Drying the plant parts of each herb and preparing the dried powder of each herb and
Myo-inositol, Microcrystalline cellulose (Plain) IP, Lactose DC anhydrous by passing
10 through 40 mesh sized sieve followed by collection of dried powder of herbs in double
line polybag;
b. Loading all the ingredients in rapid mixer granulator (RMG) followed by Starting
impeller at slow speed with chopper off followed by mixing for 10 minutes;
c. Mixing the sieved powders of all extracts in a predetermined ratio in a mixer to
15 uniform mixing;
d. Granulating the herbal extract dry mixture in RMG by gradually adding binding
agent at slow/fast impeller speed and chopper off/on at slow/fast speed followed
by addition of Isopropyl Alcohol & Water mixture if required to achieve desired
granules;
20 e. Loading the wet mass in Fluidized bed dryer(FBD) followed by air drying the
granules for a period of 5 to 10 min after heat drying the granules at a temperature
of 500C±50C to obtain desired Loss on drying(LOD);
f. Compressing Size of the dried granules through mesh 18 sieve using vibratory sifter
and collecting it in double polybags followed by Sizing the oversize granules using
25 Multi-mill through 1.5mm screen and again pass through #18 and collect in double
line polybags;
g. Sifting all the dispensed materials through mesh 40 sieve & collecting it in double
line polybags followed by blending of the Load granules and Lubricants in Octagonal
Blender for 10 minutes followed by Unloading the material in double line polybags;
30 h. Carrying out film coating of the tablets followed by packaging.
26
11) The oral polyherbal fixed dose formulation for pre-menstrual syndrome for pre-menstrual
syndrome as claimed in claim 1, wherein the said tablet composition is administered orally,
parenterally or topically.
12) The oral polyherbal fixed dose formulation for pre-menstrual syndrome as claimed in
5 claim 1 and 10 , wherein the said binding agents are selected from the group of isopropyl
alcohol; sucrose, lactose; starches, cellulose; Natural gum; Hydroxypropyl cellulose (HPC);
Xylitol, Gelatin; Polyvinyl pyrrolidone (PVP), Polyethylene glycol (PEG); Water or alcohol;
Methyl cellulose, Polyvinylpyrrolidone and Polyethylene glycol and sorbitol.
13) The oral polyherbal fixed dose formulation for pre-menstrual syndrome as claimed in
10 claim 1 and 10, wherein the said binding agent is preferably Isopropyl alcohol and Polyvinyl
Pyrrolidone.
14) The oral polyherbal fixed dose formulation for pre-menstrual syndrome as claimed in
claim 10, wherein the said dispensed materials in step (G) are selected from the group of
Crospovidone IP(XL-10), Talc IP, Sodium Starch Glycolate IP, & Vitamin B1 (Thiamin
15 Mononitrate) & Vitamin B6 (Pyridoxine hydrochloride) respectively.
15) The oral polyherbal fixed dose formulation for pre-menstrual syndrome as claimed in
claim 10, wherein the said film Coating Solution of step (H) is prepared for coating the tablets
in which IPA (isopropyl alcohol) is taken in SS Vessel equipped with mechanical stirrer
followed by addition of Instacoat universal IC-U-2959 (Transparent) slowly in it & mixing it
20 for 10min followed by addition of methylene dichloride (MDC) into solution with continual
stirring for a period of 30 min followed by filtration of the solution through mesh 100 sieve.