FIELD OF THE INVENTION
The present invention relates to a herbal composition for use in the treatment and / or prophylaxis of hypercholesterolemia, atherosclerosis, hyperlipidemia and hypertension in mammals. The composition comprises a synergistic mixture of extracts of three herbs selected from a group oi Commiphora mukul. Allium sativum and Curcuma longa,
BACKGROUND OF THE INVENTION
Babu eL al Mol. Cell Biochem. 1997, 166(1-2) 169-175 describes hypolipidemic action of Curcuma longa in streptozocin induced diabetic rats.
Dixit et. al Ind. Jour, of Pharmacol. 1988, 32(4) 299-304 describes hypolipidemic effects of Curcuma longa and Nardostachys jatamansi in triton induced hyperlipidemic rats.
Berthold et al Jour, of American Med. Assoc. 1998, 279(17) 1900-1902 describes effect of a garlic oil preparation in serum lipoproteins and cholesterol metabolism in randomized controlled trial in humans.
Yeh et, al Lipids 1994, 29(3) 189-193 describes reduction of plasma lipids using garlic.
Singh et. al Cardiovascular Drug Ther. 1994, 8(4) 659-664 describes hypolipidemic effect of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia.
Although the use of various herbs have been described in related areas, the synergistic combination oi Commiphora mukul. Allium sativum and Curcuma longa for use as agents for the control of hypercholesterolemia, hyperlipidemia and hypertension in mammals has never previously been described.
US patent No. 6,162,438 discloses an edible herbal composition for use as agents for controlling hypercholesterolemia, atherosclerosis, hyperlipidemia and

hypertension in mammals. The edible composition is a mixture of at least three, preferably at least six, herbs selected from the group consisting of Terminalia arjuna, Cynara scolymus, Zingibar officinale. Allium sativum, Crataegus oxycantha. Curcuma longa, Boerhaavia diffusa and Trigonella foenumgraecum. The composition preferably contains the herbs in approximately equal amounts.
WO 94/1894 and U.S. Pat. No. 5,707,631 are directed to a therapeutic herbal composition including Trigonella foenumgraecum seed, Syzygium aromataticum fruit, Allium sativum bulb, Cinnamomum zeylanicum bark, Saussurea costus root and Euphorbia lathyris bud; the U.S. patent discloses the foregoing herbs in combination with sodium chloride (preferably sea salt).
US patent No. 5,900,240 discloses an edible composition comprising a mixture of at least two herbs selected from the group consisting of Syzygium cumini, Gymnema sylvestre, Momordica charantia and Solanum melongena. The herbal mixtures are useful as dietary supplements and are especially useful for lowering the blood glucose level in mammals, particularly humans suffering from diabetes mellitus.
Currently there exists a great need for non-synthetic, holistic therapeutic compositions for the control of hypercholesterolemia (high cholesterol levels), hyperlipidemia (high triglyceride levels) and hypertension in mammals. It has been found that the herbal composition of the present invention are synergistic in their effect and daily ingestion of such composition is an effective therapeutic method of achieving such control without the troublesome side effects on the liver, digestive system and kidneys associated with synthetic drugs.
OBJECTIVE OF THE INVENTION

The main objective of the present invention is to provide a herbal composition for use in the treatment and / or prophylaxis of hypercholesterolemia, atherosclerosis, hyperlipidemia and hypertension in mammals.
Yet another objective of the present invention is to provide a herbal composition, which produces no adverse effects and may be taken in multiple daily doses over prolonged period of time.
SUMMARY OF THE INVENTION
Accordingly, the present invention relates to a herbal composition comprising a synergistic mixture of extracts of three herbs selected from a group of Commiphora mukul (guggul), Allium sativum (garlic) and Curcuma longa (turmeric).
In another embodiment of the present invention, the herbal composition contains pharmaceutically acceptable ingredients.
In another embodiment of the present invention, the herbal composition is useful in the treatment and/or prophylaxis of hypercholesterolemia, atherosclerosis, hyperlipidemia and hypertension in mammals.
DETAILED DESCRIPTION OF THE INVENTION
In an embodiment of the present invention, there is provided a synthetic pharmaceutical composition comprising curcumin, allin and guggulosterone and other pharmaceutically acceptable ingredients.
In an embodiment of the present invention, the curcuma extract contains 80 to 95% curcumin, garlic extract contains 2 to 4% allin and guggul extract contains 3 to 10% guggulosterone, as the active constituents.
In an embodiment of the present invention, the pharmaceutically acceptable excipients are selected from diluents, disintegrants, lubricants, binders, glidants, preservatives.

In an embodiment of the present invention, the diluents used are selected from dicalcium phosphate (DCP), microcrystalline cellulose (MCC), starch, magnesium oxide and the like or mixtures thereof
In an embodiment of the present invention, the disintegrant used is selected from sodium starch glycollate (SSG), cross-carmellose sodium (CCS) and the like or mixtures thereof
In an embodiment of the present invention, the binders used are selected from povidone, hydroxypropyl methylcellulose (HPMC) and the like or mixtures thereof
In an embodiment of the present invention, the lubricants used are selected from magnesium stearate, talc, hydrogenated vegetable oils and the like or mixtures thereof
In an embodiment of the present invention, the glidants used are selected from colloidal silicon dioxide (aerosil), talc and the like or mixtures thereof.
In an embodiment of the present invention, the preservatives used are selected from parabens such as methylparaben, ethylparaben, propylparaben; sodium benzoate, sorbic acid and the like; or mixtures thereof
In an embodiment of the present invention, the total amount of herbal extract in the composition may be present in the range of 20 to 80 % based on the weight of the composition, with the balance being the other pharmaceutically acceptable ingredients.
In an embodiment of the present invention, the individual extracts in the herbal composition may be present in the therapeutically acceptable ratio, preferable ratios are 3:3:2, 2:3:2, 3:2:2, 2:2:3, 1:1:1, 1:2:2, 1:3:3, 1:2:3 or 1:3:2,
The extract of garlic appears in light brown colour with characteristic odour which is freely soluble in water. The extract of guggul appears in light to dark brown colour, sticky to touch, which is insoluble in water. Curcuma longa extract

appears in orange yellow colour with characteristic odour, which is insoluble in water.
The herbal composition of the present invention may be used in the form of tablet, capsule, syrup, suspension, dry powders etc.
In an embodiment of the present invention, there is provided a process for the preparation of tablets or capsules containing herbal composition comprising the steps of:
i). mixing garlic, curcuma extracts and diluents,
ii). adding to the mixture obtained in step (i) a solution of guggul extract and preservatives dissolved in isopropyl alcohol,
iii). granulating the mixture obtained in step (ii) using conventional granulator iv). drying the granules using conventional drier, v). sifting the granules vi). drying the granules,
vii). adding disintegrants, glidants, lubricants and blending the mixture and viii). compressing into tablets or filling into capsules.
The tablets may be administered as such or as coated tablet. The coating may be done using conventional coating techniques such as film coating, enteric coating, sugar coating etc.
The dosage of the herbal compositions of the invention to be ingested will vary, depending on factors such as severity of the hypertension, hypercholesterolemia and hyperlipidemia, age, diet, physical condition and body weight of the patient, etc. As a general guide, it is expected that patients with a body weight in the range of 60-90 kg would ingest about 100-1,000 mg/day of the herbal compositions. It is to be understood that these dosage levels are only general guides and the proper dosage level for individual patients may vary considerably depending on the factors indicated above.

The following non-limiting examples shall serve to illustrate the mvention. Unless otherwise indicated, all amounts and parts are on a weight basis.
Example 1
GarHc (150 g), curcuma extract (100 g), microcrystalline cellulose (91.8 g) and starch (350 g) were sifted through ASTM # 40 and mixed. To this mixture, a solution of guggul extract (150 g), methylparaben (2 g), propylparaben (0.2 g), sorbic acid (1 g) dissolved in 50 ml of IPA was added and granulated the mixture using rapid mixer granulator. The granules were dried at 60 °C in fluidized bed dried, sifted through ASTM # 20, milled through multimill and sifted through ASTM # 20. To the dried granules, sodium starch glycoUate (35 g) and cross-carmellose sodium (70 g), colloidal silicon dioxide (20 g) and magnesium stearate (5 g) were added followed by blending and then compressed the blend using conventional tabletting machine to obtain tablets.
Example 2
Garlic (100 g), curcuma extract (150 g), microcrystalline cellulose (91.8 g) and starch (350 g) were sifted through ASTM # 40 and mixed. To this mixture, a solution of guggul extract (100 g), methylparaben (2 g), propylparaben (0.2 g), sorbic acid (1 g) dissolved in 50 ml of IPA was added and granulated the mixture using rapid mixer granulator. The granules were dried at 60 °C in fluidized bed dried, sifted through ASTM # 20, milled through multimill and sifted through ASTM # 20. To the dried granules, sodium starch glycoUate (35 g) and cross-carmellose sodium (70 g), colloidal silicon dioxide (20 g) and magnesium stearate (5 g) were added followed by blending and then compressed the blend using conventional tabletting machine to obtain tablets.

The herbal composition of the present invention lowered random triglyceride, cholesterol and increased HDL. This was demonstrated by in vivo animal experiments.
Triton induced hyperlipidemia
The systemic administration of the surfactant triton to rats resulted in elevation of cholesterol and triglyceride. Wistar rats weighing 180 to 200 g were starved for 18 hrs and then injected intraperitoneally 200 mg/kg of triton. The test drugs were administered simultaneously along with triton. The blood samples were collected at the time intervals of 24 h and 48 h after the administration of the herbal composition and the blood cholesterol, triglyceride and HDL levels were calculated using the conventional formulae. The results are shown in table 1.

Plasma lipid profile in diet induced atlierosclerotic rats
Male Wistar albino rats weighing between 100 to 125 g were used for this study. Cholesterol rich diet was fed for 5 weeks, then the drug was administered once

daily for 7 days with free access to regular food and water. The plasma samples were collected and cholesterol, triglyceride, VLDL, LDL and HDL levels were calculated using the conventional formulae. The results are shown in table 2.

Plasma lipid profile in diet induced hypercholesterolemia in Rabbits
White New Zealand rabbits were supplemented with 2% of cholesterol and at this regiment for a period of 10 weeks. Drugs were administered as a fine suspension on 0.3% CMC and administered orally using oral catheter tube, once daily during the last four weeks of the study. The blood was withdrawn from the ear marginal vein before and after treatment and the plasma was separated to estimate the blood lipid profile. The results are shown in table 3.

We claim :A
1. A herbal composition comprising a synergistic mixture of extracts of three herbs selected from a group of Commiphora mukul (guggul), Allium sativum (garlic) and Curcuma longa (turmeric),
2. The herbal composition as claimed in claim 1, contains pharmaceutically acceptable ingredients selected from diluents, disintegrants, lubricants, binders, glidants and preservatives.
3. The herbal composition as claimed in claim 2, wherein the diluent used is selected from dicalcium phosphate (DCP), microcrystalline cellulose (MCC), starch, magnesium oxide or mixtures thereof.
4. The herbal composition as claimed in claim 2, wherein the disintegrant used is selected from sodium starch glycoUate (SSG), cross-carmellose sodium (CCS) or mixtures thereof.
5. The herbal composition as claimed in claim 2, wherein the binder used is selected from povidone, hydroxypropyl methylcellulose (HPMC) or mixtures thereof
6. The herbal composition as claimed in claim 2, wherein the lubricant used is selected from magnesium stearate, talc, hydrogenated vegetable oils or mixtures thereof
7. The herbal composition as claimed in claim 2, wherein the glidant used is selected from colloidal silicon dioxide (aerosil), talc or mixtures thereof

8. The herbal composition as claimed in claim 2, wherein the preservative used is selected from parabens such as methylparaben, ethylparaben, propylparaben; sodium benzoate, sorbic acid or mixtures thereof.
9. The herbal composition as claimed in claim 1, wherein the total amount of herbal extract in the composition present in the range of 20 to 80 % based on the weight of the composition.
10. The herbal composition as claimed in claim 1, in the form of tablet, capsule, syrup, suspension, dry powder.
11. A pharmaceutical composition comprising curcumin, allin, guggulosterone and other pharmaceutically acceptable ingredients.
12. The pharmaceutical composition as claimed in claim 11, wherein the curcumin is extracted from curcuma extract, allin is extracted from garlic extract and guggulosterone is extracted from guggul extract.
13. The pharmaceutical composition as claimed in claim 12, wherein the curcumin in curcuma extract is about 80 to 95%, allin in garlic extract is about 2 to 4%, guggulosterone in guggul extract is 3 to 10%.
14. A process for the preparation of tablets or capsules containing herbal composition comprising the steps of:
i). mixing garlic, curcuma extracts and diluents,
ii). adding to the mixture obtained in step (i) a solution of guggul extract and
preservatives dissolved in isopropyl alcohol,
iii). granulating the mixture obtained in step (ii) using conventional granulator

iv). drying the granules using conventional drier,
v). sifting the granules
vi). drying the granules,
vii). adding disintegrants, glidants, lubricants and blending the mixture and
viii). compressing into tablets or filling into capsules.
15. A method for the treatment and / or prophylaxis of hypercholesterolemia, atherosclerosis, hyperlipidemia and hypertension in mammals comprising administering the herbal composition as claimed in claim 1 to a patient in need