Indian Patents. 235326:A PROCESS FOR MAKING A COMPOSITION CONTAINING A PHARMACOLOGICALLY AND/OR BIOLOGICALLY ACTIVE PLANT EXTRACT

Title of Invention	A PROCESS FOR MAKING A COMPOSITION CONTAINING A PHARMACOLOGICALLY AND/OR BIOLOGICALLY ACTIVE PLANT EXTRACT
Abstract	A process for making a composition containing a pharmacologically and/or biological active plant moringa oleifera linn extract suitable for administration in a convent dosage form useful for the treatment of hypercholesterolemia, mixed dyslipidemia, hypertriglyceridemia and other clinical disorders associated with lipoprotein metabolism comprising the steps

Full Text	FIELD OF INVENTION This invention relates to a process for making a composition containing a pharmacologically and/or biologically active plant extract suitable for administration in a convenient dosage form useful for the treatment of hypercholesterolemia, mixed dyslipidemia, hypertriglyceridemia and other clinical disorders associated with lipoprotein metabolism Particularly, the present invention is directed to provide a composition in a convenient dosage form, useful in restoring and maintaining a satisfactory lipid profile in an animal body, including the human body, and typically having the pharmacotherapeutic activity of increasing high density lipoproteins, and lowering low density lipids and triglycerides. DESCRIPTION OF THE BACKGROUND ACTIVITY OF THE ART For utilization and storage of the fat absorbed from the diet and lipids synthesized by the liver and adipose tissue, they have to be transported between the various tissues and organs. Storage and transportation poses a problem since lipids, being nonpolar. Are insoluble in blood plasma, which is typically an aqueous environment. The body solves this problem by combining the hydrophobic lipid moiety with amphipathic lipids such as phospholipids and cholesterol and proteins to form water miscible lipoprotein molecules. In the anabolic phase of their feeding cycle, omnivores, such as humans, ingest excess calories. This phase is followed by a negative phase in which the animal draws upon its cryohydrate and fat stares. This cycle is mediated by Lipoproteins involved in transporting lipids from the intestines as chylomicrons and from the liver as Density Lipoproteins(VLDL) to the adipose tissue for storage and to the other tissues for oxidation. The final stage in the catabolism of VLDL results in Low density Lipoproteins (LDL) also called Beta-Lipoproteins Also involved in an intermediate stage of VLDL and chylomicron metabolism and cholesterol transport is another lipoprotein known as the alpha-lipoprotein or HDL. In both LDL and HDL, cholesterol and phospholipids airs the predominant lipids. TriacyIglycerol (also known as triglycerides TG) is the predominant lipid moiety in chylomicrons and VLDL. Thus Chy1comicrons transport TG from digestion and absorption of dietary lipids. VLDL transport TG from the liver to the tissues. LDL are cholesterol rich and result from the metabolism of VLDL and act as a mediator and Are involved in depositing cholesterol in the tissues and HDL are cholesterol rich but are involved in removing cholesterol from the tissues to the liver for conversion to bile salts. Cholesterol plays a major role in the genesis of artherosclerosis of vital arteries and which, when the coronary arteries are involved, may lead to ischaemic heart disease. It must be understood that only half the cholesterol of the body is provided by the average diet. The other half is synthesised within the body itself. All tissues containing nucleated cells are capable of synthesising cholesterol. The liver accounts for 10"/. of this synthesis, the gut 15"/. and the skin almost 20%. Because of its propensity to dump cholesterol on the arterial walls, LDL has been labelled as the 'bad' cholesterol whereas HDL' because it tends to scrape away cholesterol from the vessels and carry it to the liver has been labelled as the 'good' cholesterol. The role of TG in artherosclerosis is as yet unclear. Of the serum lipids Cholesterol is most often incriminated as a risk factor in coronary heart disease (CHD). Parameters such as serum TG, VLDL and LDL have also been incriminated. The Framingham study has demonstrated a linear increase in coronary 'risk' with increment of total plasma cholesterol level from ISO mg!; upwards- a 1'/. fall in cholesterol predicts a 2% reduction in CHD risk. LDL as the carrier of 70% of the total cholesterol to the tissues is the most potential atherogenic agent. On the contrary an inverse relation between CHD and HDL concentration has been found. A raised HDL concentration is beneficial and protective against CHD. This protective mechanism is explained by two mechanisms operating in parallel: (a)'reverse transport's the scavenging action of HDL by which the intracellular cholesterol content is reduced by HDL transporting Cholesterol to the liver from the tissues for degradation; and (b)control of TG catabolism. An increase in HDL concentration is associated with a faster elimination of TG and its artherogenic intermediates. Elevated TG is suggestive of a less effective intravascular lipolysis and hence in the reduced formation of HDL, HDL has shown to competitively inhibit LDL binding an uptake. Thus 4 decreased plasma levels of HDL tend to increase LDL uptake, while increased levels of HDL decrease cellular uptake of JPL. It has na\,-4 been postulated that the ratio of LDL cholesterol and HDL cholesterol is important in predicting the onset of CHD, If the ratio is high the risk is more. To predict a minimal risk of CHD the following determinant readings have been suggested A total serum cholesterol reading less than 200mg/dl A serum LDL reading less than 130 mg/dl A serum HDL reading greater than 35 mg/dl. A serum TG reading less than 200 mg/dl Any variance in the above readings in the lipid profile of an individual will require effective ways to modify the profile to achieve the minimal risk parameters prescribed. The first step to achieve a desired lipid profile is to resort to dietary and life-style changes , Dietary changes include the consumption of less fat, particularly animal and dairy fat and other saturated fats. Merely cutting down on dietary cholesterol is not a critical factor. Eating more soluble fibre, such as oat bran and generally reducing obesity if present. Life style changes include moderate aerobic and nonaerobic exercises, stopping smoking, regulating meal times and reduction of stress. If Dietary changes and Life style changes are not have been attempted for a period of six to eight months and have been found to be ineffective, drug therapy is resorted to. If this option is exercised, it is generally tailored to match the particular individual's lipid profile. It is therefore clear that the atherosclerotic process is enhanced by increased blood cholesterol level. The frequent association of ischaemic heart disease with hypercholesterolemia, dyslipidemia has stimulated search for substances which reduce blood cholesterol level. Many such substances were discovered but they 3i.re reported to have adverse side effects and other disadvantages. Hence they could not be advocated for use in daily life. Efforts were made to isolate a promising hypocholesterolaemic agent out of the substances taken in routine diet, leather et al. reported hypocholesterolaemic activity of Cicero anetirium in albino rats and rabbits. Gupta and Mehrotra demonstrated that oral administration of onion lowered the experimentally induced alimentary lipaemia in human beings. Bordia et al. has reported the protective action of garlic and onion in human subjects against fat induced hypercholesterolemia. Different therapies have been suggested for lowering cholesterol, in general and modifying the lipid profile as a whole. These includes Niacin 3 This B vitamin is the most effective cholesterol lowering drug. Its cholesterol lowering action is unrelated to its vitamin action. It is required to be consumed in large doses: over 4 to 5 grams per day and over a period of time it raises HDL and is especially useful in lowering TG and LDL. However it has moderate side effects including severe generalised intense skin flushing, These drugs can lower LDL but also at the same time lower HDL. Their side effects include gastrointestinal bloating and gas, decreased absorption of fat soluble vitamins Gemfibrozi1; It has modest effects on LDL but is effective in lowering TGH and raising HDL. Side effects include abdominal and epigastric pain, nausea and vomiting, known interaction with anticoagulants, HRT; Hormone replacement therapy can raise HDL and lower LDL but the side effects include a risk of breast cancer. Plants halving pharmacological and biological activity have been the basis of treatment of human diseases for centuries. Use of pharmacologically or biologically active plant extracts is well-known. It is also known that the biologically or pharmacologically active compounds can be isolated and purified from the plant extract to obtain therapeutic compositions. There are reasons to believe that plant extracts having pharmacologically and biological activity can serve as a good source of lipid profile modifying agents. It is suggested that the plant extract identified in the present invention will provide short and long term benefits to patients having clinical disorders associated with Lipoprotein metabolism and an undesirable Lipid profile with the concomitant lowered risk of CHD and artherosclerosis as a result of its lipid profile modulating activity and other supportive activity. The drugs used at present have limited advantages and their effects are mainly of short term duration and there are many disadvantages in the use of these drugs over extended periods of time. Further the drugs used at present are costly and have low benefit-risk ratio. The ideal compound to modify the progress of the disease has not yet been found hitherto fore. This invention therefore specifically relates to a plant extract composition for the treatment of hypercholesterolemia, mixed dyslipidemia, hypertriglyceridemia and other clinical disorders associated with lipoprotein metabolism. OBJECTS OF THE PRESENT INVENTION A further object of this invention is to provide a composition aforesaid that acts without exerting toxic or side effects. Still another object of this invention is to provide a disease-specific synergistic composition, in convenient dosage form. A further object of the invention is to provide a method of treatment of clinical disorders associated with lipoprotein metabolism, elevated undesirable cholesterol levels and specifically hypercholesterolemia,mixed dyslipidemia and hypertriglyceridemia, - a method which, unlike present available treatment which usually have severe side effects, demonstrates little in the way of side effects. SUMMARY OF THE INVENTION According to this invention there is provided a method of treating clinical disorders associated with lipoprotein metabolism, elevated undesirable cholesterol levels and specifically hypercholesterolemia,mixed dyslipidemia, and hypertriglyceridemia, in an animal, typically a human, comprising administering to the animal, typically enterally, in a convenient dosage form, a therapeutically effective amount of the extract of the plant in a predetermined proportion with or without other biologically active inorganic ingredients . In accordance with this invention there is provided a process for making a composition containing a pharmacologically and/or biologically active plant extract suitable for administration in a convenient dosage form useful for the treatment of hypercholesterolemia, mixed dyslipidemia, hypertriglyceridemia and other clinical disorders associated with lipoprotein metabolism comprising the steps of : cleaning fruit of the plant Moringa Oliver limn; cooking and cooling for 10 to 20 minutes; drying the cooked fruit; articulating the dried fruit and sieving through 60 mesh size; converting a therapeutically effective amount of the particulate matter in a predetermined proportion with or without other biologically active ingredients into a consumable pharmaceutical vehicle, such as a capsule a tablet , oral liquid and the like . Typically the process a step in which tender or semi ripe fruits are selected for the process and tips at both end, typically 2 to 3 cms are cut off before cooking. Further , the fruit is cut into pieces about 4 cm long before cooking done by steaming in a pressure vessel. Drying is done at room temperature or at 60 degrees celsius, typically in a an oven. Typically, the oven may be of the forced hot air type , the steam jacketed type or the electrically heated type oven. The cooked fruit either before or after drying is slit open to expose the pulp and seeds and the pulp and seeds are scrapped from the jacket and the dried mass of pulp and seeds is pulverized to obtain particulated matter which is sieved through a 60 mesh sieve. The powder so obtained is then converted into a. pharmaceutical dosage form in a conventional manner. DETAILED DESCRIPTION The invention provides a method of treating clinical disorders associated with lipoprotein metabolism, elevated undesirable cholesterol levels and specifically hypercholesterolemia,dyslipidemia, and hypertriglyceridemia, in an animal, typically a human, comprising administering to the animal, typically enterally, in a convenient dosage form, a therapeutically effective amount of the extracts of the plant Moringa Oleifera Linn in a predetermined proportion with or without other biologically active inorganic ingredients the said composition made in accordance with a novel process which is hereinafter disclosed. Habitat„-A beautiful tree(plant) in the sub-Himalayan range and commonly cultivated in India and Burma. It is a very popular backyard tree that grows over nine meters tall. It has a soft white corky trunk and branches bearing a gummy bark. The leaves are trippnately compound bearing several small leaflets. The flowers are white. The long slender fruit is a many seeded pod in the shape of a 'drumstick' and the seeds are three winged. Propagation is by wind. The flowers, Itender leaves and fruit pods are eaten as a vegetable or made into a pickle. Parts Used,- Carbohydrate 14 g. Vitamin A 11, .235 I.U. Protein b g ■ Vitamin B2 59 meg, Fat O g- Niacin 0,7 mg , Calcium 425 mg. Vitamin C 217 mg. Phosphorus 70 mg, Digesting T ime 2 Hrs. Iron 7 mg, CALORIES 84 constitution: Hot and Dry 3, Physiopharmacology and Therapeutics Moringa or Horse radish tree grows all over India and Pakistan. It is beautiful tree mostly grown as a backyard tree in most of the South Indian homes for its drum-stick like fruits, tasty flowers and the leaves that are cooked and eaten as vegetable. Leaves Moringa leaves are not very popular as market vegetable, because majority of us think that the leaves are hot and not nutritive but the chemical analysis of the leaves shows that Almighty God has treasured enormous nutritive wealth in these cheap and discarded leaves. Fresh juice of the leaves supplies the following vitamins and minerals having comparative value of other foods: Vitamin A Fresh juice 1 cup full supplies as much vitamin A as one gets by eating any one of the following foods: eggs 9 Mutton 16 kg. Sheep's liver 50 g. Butter 500 g. Shelled almonds 1 cupful Fresh Cow's milk 80 cups. Vitamin C Equal to: Oranges 6 Limes 6 Apples 8 Mangoes 20 Bananas 16 (Langra Variety) 3 Grapes 2„5kg. Water melon 7.5kg. Calcium A handful of fresh leaves supply as much calcium as one gets by eating any one of these foods: Almonds 900g. Chicken roast 3kg. Oranges 8 Eggs(hen's) 20 Papaya 3.5kg. Mutton chops 2.5kg,etc Drum-stick leaves are a rich source of all the essential amino acids. Young leaves are used as food. Leaves ground into a paste with a few pods of garlic, a. bit turmeric, salt and pepper are given internally in scurvy, catarhal affections, and in cases of dog-bite are applied externally over the bite. In 5 to 6 days the wound will heal, the inflammation and the febrile symptoms subsiding. Leaf-juice is dropped into the eyes in fainting fits due to nervous debility, spasmodic affections of the bowels, hysteria, flatulence etc; mixed with honey it is applied as ajar to the eyelids in eye diseases. A quarter seer of leaf-juice mixed with one toga of saindhava is given in excessive urinary secretions. In cases of headache the juice of leaves with black pepper rubbed tin to it is applied warm to the aching parts. Leaf-juice in doses of 4 tolas is given as an emetic. Poultice of the leaves is useful in reducing glandular swellings. It always produces a blister . It is estimated that lOOg.of the leaves contain the following concentration in grammes. DRUM STICK LEAVES Arginine 6 Histidine 2.1 Isoleucine 6.3 Leucine 9.3 Lysine 7.6 Methionine 2 Phenylalanine Thereonine Tryptophan Valine 6.4 4.9 1.9 7.1 A glassful of durm stick leaves-soup supplies as much protein as one gets by eating any one of the following foods approximately: Beef lOOg. Fish 120g. Chicken lOOg. Pork lOlg. Milk 2.5cups Eggs 2 Soup of the leaves prepared by immersing a handful of tender leaves in boiling water 6 02.for 5 minutes with a lid on the vessel and after this period the vessel is immersed in cold water so as to cool the soup quickly. To this soup a pinch of salt, pepper, lime juice half teaspoon is added and drunk every morning as a tonic medicine to get protection against, malnutrition, anaemias, tuberculosis, asthma, seasonal attacks of colds and bronchitis, pre-mature oldage,pre-mature loss of strength and vigour,nervousness, functional sterility in ma1es and fema1es, etc. A teaspoon of fresh-leaf juice mixed with honey and a glassful of tender coconut water, is given two to three times as a herbal medicine during the treatment of cho 163ra,dysentery ,diarrhoea, colitis, jaundice,etc. A cupful of the fresh leaf-juice coagulated by heating it gently on water bath, and then the clear fluid is filtered. It is mixed with milk instead of water and the infants and children are fed once day to help them grow healthy with strong bones, pure blood and develop high resistance against infection and malnutrition. The same tonic-medicine can be regularly used during all times by all irrespective of age. Its regular use during pregnancy and lactation, helps the mother to get extra calcium,iron,vitamins at no cost and also helps the healthy development of the baby with strong nerves and bones. It acts on the uterine contracting mechanism and prevents sluggishness of uterus which we call Uterine Inertia and eases child birth reducing severe blood loss and post-partum complications.Its regular use after child birth increases breast milk and helps the mother to recover quickly from lying-in-period.A tablespoon of coagulated fresh leaf-juice mixed with a glass of fresh-juice of cucumber or carrot is an effective medicine for scanty urination, constant burning in urethra due to high acidity of urine,myxoedema,toxaemias of pregnancy,dropsy due to heart,liver,kidney disorders, hypertension, excessive thirst due to summer heat, diabetes, constipation,etc. A teaspoonful of the juice with Rock-salt 10 g,once daily is used to cure excessive’ urination of non-diabetics. Fresh juice 1 tablespoonful with honey,taken every night before going to bed cures; night blindness,weak memory,loss of smelling power,poor hearing etc. Taken with lime juice cures vert igo, b 1 eed.i nn ni1f2rlinn frnm 1iinn=r, AHH nose, hiccough., biliousness, indigestion, morning sickness,malabsorption syndrome etc. A teaspoon of the fresh juice with salt is given as an emetic to weak persons and children suffering from excessive gas. A teaspoon of ghee prepared by clarifying with fresh leaves as handful per blob butter is given as a tonic for children. Fresh leaf-juice is instilled in the eyes to cure fainting fits due to nervous debility corneal ulcers,burning and itching in eyes, flickering and twitching of the eye lids, failling of the eye lashes, night blindness due to vitamin A deficiency etc. Juice is instilled in the nose to cur syncope ( E’havaprakash 3 . Leaf juice mi;ced with equal quantity of radish-leaf juice is applied over piles with gratifying results. Juice mi;;ed with til oil and heated to evaporate the watery content and the oil is applied as a medicine to cure scabies, rheumatism, sprains and contusions. Roasted leaves are: fomented to reduce pain and inflamation caused by injuries, and to reduce the water content of hydrocele. Fresh leaf juice with a pinch of turmeric powder is applied to extract guinea worm. As a first aid dressing in dog bite, leaves Slurs pounded, with few cloves of garlic and a pinch of turmeric; the wound is cleaned vita0 pre-boiled water and the mixture is applied. (It must be remembered that dog bite causes serious complications such as tetanus even if the dog is not rabid. If bitten by a mad dog,, rabies is sure to develop, therefore, all dog bites must be treated carefully with a full course of 7 to 15 Anti-Rabies-injections that are given free in all the Govt.dispensaries and hospitals.) Fresh leaf juice applied with lime juice cures pimples, black heads and keeps one's face flower fresh. A teaspoonful of the fresh leaf juice mixed with 3 peppers is applied over temples to cure head-ache. An ounce of the fresh leaf-juice acts as a safe emetic in chronic bronchitis, asthma etc.(for adults only). Poultice of the fresh leaves is applied over glandular swellings. It reduces pain due to its counterirritant action (Allowing the poultice for a long time causes blisters.) Fruits: Green coloured elongate fruits with striations and multipoded seeds, length 30-45 cms and diameter 1-2 cms Fruits like long sticks are nutritive aphrodisiac. They 3.re cut into desired pieces and cooked as vegetable are usually eaten during their harvest time in summer. Soup of the tender pods have been used as a medicine for rheumatism, colds, impotency, small urinary stones, weakness of the nerves, enlargement of liver and spleen, constipation etc. Regular use of the pods prevents the infection from round and pin worms. Soup mixed with honey is given as a food-medicine for paralysis,Bel 1's Palsy Jhemiparesis etc. It rectifies the menstrual irregularities. Pickles of the raw fruits prepared with pure vinegar is useful in curing lumbago,sciatica. paralytic stiffness of the limbs,, rheumatism etc. Eating the fruits cooked with unripe mango, reduces summer heat in the body and prevents iron and vitamin C deficiency, "The pods (fruits) made into a soup are prescribed by Hakims as a diet in sub-acute cases of enlarged liver and spleen" I, particular pains, tetanus, debility of nerves, paralysis, pustules, patches,leprosy etc. Young, unripe pods, known as drum sticks, area favourite ingredient in curries, and they act as a peventive against intestinal worms. Seeds of the pods ground with water and instilled into the nostrils cure headaches due to cold and excess of K'afa. They 3.re given in cases of ascites resulting from enlargement of the liver and spleen. : Nutritive value of Drumstick ( Moringa Oleifera fruit) Ed i b1e portion: 83% Moistures 86.9X Proteins 2.5"/. Fat; O.iy. Minerals 2.0% Fiber 4.8% m d rates; 3.7% calories 26 per lOOg of edible portion Flowers Flowers Are hot and dry in constitution. They are cooked and use as vegetable. Flowers boiled in milk and re used as a se;;-tonic to cure impotency in young persons. Fresh juice of the flowers 1 tablespoon with butter milk one glass is given as a medicine to cure asthmatic attacks, scanty urination, indigestion, gravel in bladder. Juice given twice with tender cocoanut water acts as a diuretic tonic-medicine during the treatment of nephritis, congestive heart failure, urethritis, cystitis, Flowers or leaves soaked in vinegar are used with food or they 3.re made into curries which are very wholesome. Bark: The corky-bark is grey and is about an inch thick. It is acrid with pungent taste and yields a coarse fibre. Bark contains a white crystalline alkaloid(occurring in the spirituous extract), 2 re5ins(one soluble and the other (insoluble in ammonia), an inorganic acid,mucilage(gum) and ash S p.Cn Bark of the stem and the roots used in Omani and Ayurvedic medicine for various ailments. Col.R.N.Chopra and De analysed the chemical contents of the bark and they found the following chemicals: Myristic acid 7,3 per cent Oleic acid 7.3 per cent Palmitic acid 10.8 per cent Lignoceric acid 3 per cent Behenic acid 8.9 per cent Phytester1 9 per cent Stearic acid 10.8 per cent The scientists, also extracted various useful alkaloids such as: the platinic chloride having yellow rectangular plates with melting point 221 and the picrate having yellow wooly needles with 195 melting point. The pharmacological action and therapeutic uses of these alkaloids prepared from the bark of Moringa P. were also clinically tested at Calcutta Tropical School. The resea,rchers confirmed that the crystalline bases have no marked physiological action, whereas the Amorphous base. sympathetic nerve endings of the entire human nervous net. By its stimulating action, it constricts the blood vessels and elevates the blood pressure, accelerates heart-beat. Its main action on the heart is due to direct stimulation of cardiac sympathetic nerves, but the myocardium may be slightly affected. The researches also observed that the amorphous base inhibits the tone and the movements the involuntary muscles of the gastrointestinal tract and bronchioles. The stimulant action of this base was also found in other organs. It produces slight diuresis, dilates pupils and is destroyed in the liver. Large doses of this base produce depression in voso-motor nerve endings. However, its sympathomimatic action cannot be compared to Adrenaline, Considering the facts of the above research the powder of the dry bark 4 ounces is boiled in a pint of water for about half an hour and an ounce with a teaspoonful of honey taken three times daily after food for a month cures impotency, pre-mature ejaculation, thinness of semen, scanty menstruation in young anaemic girls, asthma, bronchitis, with severe cough,scurvy,etc. The bark 1 oz. is boiled with a handful of tender bamboo shoots in 18 ounces of water until 8 ounces remain. This decoction 2 ounces taken four hourly for 2 days acts as an abortifacient. An inch long piece of bark boiled and trimed to make as a pessary is inserted in the os to induce abortion in folk medicine (such attempts in lay hands causes grave risks). Rouring warm decoction of the bark over paralytic limbs improves blood circulation and reduces stiffness. A handful of the fresh bark is pounded and in or coconut oil 12 ounces Mustard seed 1 tablespoon and bailed till the bark begins to turn brown, later the oil is cooled strained and preserved in a bottle. It is applied as an analgesic liniment in painful conditions of the joints, due to rheumatism, sprains, ritis,etc. Few drops of the oil mi;!ed with some plain coconut oil is applied over the scalp to lengthen hair and prevent hairfall. A hole is made in the stem of the tree and a full cut circular betel nut is inserted and the hole is closed with wheat flour paste to keep it secure. After 2 months, the nut is taken from the stem and preserved. A piece of it if held under the tongue during intercourse prevents pre-mature ejaculation. The absorption of lignoceric acid in the circulation acts on the time mechanism of semen ejaculation and helps in delaying the passing of ejaculatory transmission. Warm juice of the stem bark 5 drops is put in the ear to stop ear ache due to exposure to breeze. In Efengal half-ounce doses of the bark are said to be used to procure abortion. Root Root of durm stick tree resembles like European Horse-radish in smell and appearance. Its bark is pungent and has more medicinal value than the bark of the stem. Root yields an essential oil very pungent and offensive in odor. Decoction or the tincture of the root bark prepared by adding equal parts of orange peel with a pounded nutmeg is given half to 1 teaspoon thrice daily after meals as a carminative medicine in spasmodic conditions of bowels, flatulence. In hysteria, dizziness, nervous debility, the same may be used with good results.3 Decoction of the roots mixed with pepper 2, garlic 3 cloves and honey is given an ounce thrice daily as medicine for intermittent fever, malaria, epilepsy, gout, dyspepsia, flatulent colic,ascitis enlargement of liver and spleen etc.2,4,5. In soreness of the mouth, decoction of the roots is gargled. In carried tooth, finely powdered root is filled. It must be noted that once the hard enamel of the tooth is damaged, it is not possible to regenerate it again Therefore, to get permanent relief, one is advised either the tooth be filled or extracted. Decoction of the fresh rootd in 20) taken an ounce thrice daily for a month along with cardamom 1, before food, cures hiccough, hysteria, lumbago, rheumatoid arthritis, etc,4 Taken with honey once at 6 p.m., and another dose at 10 p.m.,cut shorts the severity of asthmatic attacks 5. Regular use of the decoction(1:20) 1 ounce thrice daily with Asafoetida 2 grs. is said to cause abortion in early pregnancy. (In my opinion, it may not be useful in genuine pregnancy, taut may tae used in delayed menstruation due to lack of progestrone, primary amenorrhoea and uterine inertia). Fresh Juice boiled in water and a little salt is added to this decoction, is gargled in sore-throat, relaxed uvula, pharyngitis, hoarseness of the throat etc. Paste of the roots mixed with a teaspoonful of seed is applied as a very useful liniment to cure rheumatic pains, inflamatory swellings and tumours, paralytic parts, sprains, dislocations etc. Fresh juice 5 drops is put in ears to cure BAr ache2. Paste of roots prepared with water is applied over scabies, ringworm, itching of the skin due to its dryness etc. Seeds Dry seeds of moringa are nutritive and contain a very-useful commercial oil known as Ben oil. The husked seeds yield "on simple pressure a clear, limpid, almost colourless, rather thick at ordinary temperature" fixed oil 36.6 p.c, known as Beni or Ben or Moringo oil. It contains 60 p.c. of liquid oil and 40 p.c. of white solid fat. European grated horse-radish contains sulphur. 24 It contains Myristic acid 7.3 per cent, Palmitic acid 4.2 per cent. Oleic acid 65.8 per cent, Stearic acid 10.8 per cent,, Behenic acid 8.9 per cent and Lignoceric acid 3 per cent. 9 per cent of Phytoserol in the oil. The oil contains about 3.7 per cent unsaponifiable matter. Ben oil is a clear liquid which is rather thick at room temperature. Its specific gravity is 0.912 to 0.915 at 60F. It has not taste and smell. It does not turn rancid and saponifies very slowly. Therefore, it is an ideal medium for lubricating delicate machine parts like watches, cameras,, etc. Perfumers esteem the oil for its great power of absorbing and retaining even the most elusive odours. Ben oil mixed with ground-nut oil is used externally with very gratifying results in the treatment of rheumatism, gout etc. The oil is found to be a good source of a Behenic acid in nature; Behenic acid was synthesised from n-cicosanic acid, and also by the hydrogenation of methyl eru.cate and finally hydrolysing the resulting methyl behenate„-( V.C.Parekh, Indian Institute of Scie’nce, Bangalore) Paste of the dry seed is applied in the vagina half an hour before conjugal union to increase the voluptuous feelings in both the partners. It acts as a safe contraceptive if used with little salt and honey and inserted along with a tampon before sexual intercourse. Seeds of the fresh pods 25 head-ache due to coldB. Paste of fenugreek infusion and honey is given thrice daily for a month to cure ascitis caused by liver derangement. Paste of the seeds is applied over glandular swellings. Gum Gum of moringa is opaque and white when it first comes from the trunk, but soon becomes pinkish dark on exposure to air. It is bland and nucilaginous and becomes friable in dry air and is tough in damp air. It holds 20 per cent of its weight of water. The gum is insoluble in water. The amount of bases present in the alkaloid are very small and its practical utility in therapeutics is doubtful unless the quantity of active principles is increased by suitable cultivation. Gum is used as a medicine to cure spermatorrhoeaj excessive menstruation in anaemic girls2, etc. Usually about 20 gr. of the gum is fried in ghee and is used with sugar and milk for the above said complainst. Fried gum is also used to cure flatulence, head ache. Fresh liquid like gum mixed lime juice is applied over painful conditions of the joints, glandular swellings, etc. Boiled with castor oil is used as an analgesic medicated oil in rheumatism paralysis,neuritis etc2. Gum mixed in til oil is put in ears to alleviate ear ache. Mixed with milk gum is rubbed to cure head ache, arthritis, butaos, painful bones in syphilis. Gum is inserted in the external os to cause abortion. 26 'usting with DuD.T. powder over the tree prevents the reeding of hair caterpillars, that the commonly found on he stem. Touching them causes serious allergy and contact esuratitis. These worms thrive well on the sap of the tern bark and leaves. General Action.-Antispasmodic, stimulant, eKpectorant, and diuretic. Fresh root is acrid and vesicant5(has the taste of horse-radish); internally stimulant, diuretic and antilithic. Gum is bland and mucilaginous seeds are acrid and stimulant. Bark is emmenagogue and even abortifacient. Flowers .’re stimulant, tonic and diuretic and useful to increase the flow of bile. Mahomedan Writers describe the flowers as hot and dry. The plant is acardiac and circulatory tonic and antiseptic. Pharmacological Action-"The pharmacological action of the vegetable bases isolated from M.pterygosperma worked out by Chopra ?■; De:-"The crystalline base has little or no physiological action, whereas the amorphous base shows marked activity and closely resembles adrenaline and ephed rine in its effects. This base thus belongs to the sympathominetic group of bases. It acts on the sympathetic nerve edings all over the body producing a rise of blood pressure, acceleration of heart-beat and constriction of the blod vessels. Its effect on the heart is mainly through the sympathetic though the myocardium may also be slightly stimulated. It also inhibits the tone and movements of the involuntary muscle of the qastro-intestinal tract and the bronchioles. The effects sympathetic stimulation i-gere also found in the action of this base on other organs. It produces slight diuresis on intravenous injection in animals, dilates pupils and is detoKicated by the liver.. ‘Jery large doses depress the vasomotor nerve-enmdings» This base differs from adrenaline in that it produces littbe or no rise of blood pres£?ure after ergotoxina, whereas adrenalne produces a fall under similar conditions. The sympathomimetic base isolated from M.pterygosperma is, however, very much weaker in its action than adrenaline or ephedrine. Action H: Users in Ayurveda and Siddha-Mathura Katu, Kashaya, rasam, Ushna veeryam, Katu-vipakam; Bark.-Emmenagogue. Seeds.-Aphrodisiac; Flowers.-leaves and root:-Anthelmintic,giddiness,nausea, pitta diseases, astthi Jwaram,T„B.-(Therapeutic Notes). Action &. Uses in Unani.- Murakab-ul-khuva :-la;::ative, anti-spasmodic; leaves external-laryngitis.-(Therapeutic Notes). Usess.-Leaves, flowers, immature capsules and root 3.rB eaten as vegetables in curries. Grated horse-radish (European) eaten at frequent intervals during the day and slo at meals will banish the distressing cough that lingers after influenza. As it contains sulphur, it is recommended for rheumatism, ascites and venomous bites; applied as a poultice for neuralgia of he face. Root of the drumstick tree resembles in odour and appearancce that of horse-radish of Europe, for which its is said to be a perfect substitute. A compound spirit made in the usual way of equal parts of Morinaa root and oranqe peel with a and heat the plate at 120 degree C for 5 minutes, A Yellowish brown spot with Rf value of 0,.i>2 will be visible which is comparable with that spot obtained with Working standard. Dosage forms: The dried pulp bulk prepared from Moringa Oleifera Lam, fruit (Drum stick) is used to prepare various dosage forms. Each formulation had 100 mg to 500 mg of the dried pulp bulk prepared from Moringa Oleifera Lam per unit dose. Capsules: The dried pulp bulk is sufficiently free flowing for hard gelatin capsule formulation. However, different excipients like Lactose, Starch, Talcum, Magnesium Btearate Etc., in suitable proportions 3.re also employed for facilitating the capsules preparation. Tablets s The dried pulp bulk is used in conjunction with different conventional excipients in compressing into tablet dosage form. For this purpose bath wet and dry granulation is employed. These tablets have good disintegrating properties, meets with the other parameters of tablet evaluation like hardness, friability, etc. 36 Oral Liquids; The dried pu1p buIk is used in formu1ation of oral liquids. li The dried pulp bulk is suspended in a syrupy base with suitable preservatives yielding a homogeneous suspension. 2. The dried pulp bulk is suspended in a non-syrupy base with suitable preservatives yielding a homogeneous suspension. 3. The dried pulp bulk is prepared into Dry Syrup with suita\ble preservatives. When constituted yields a homogeneous suspension. OTHERS Dosage forms which Bre also envisaged under this invention includesRectal suppositoriesj Injectable formulations like intramuscular, intravenous preparations, Effervescent tablets. Pharmacological Activity discovered: Hypocholesterolemic and Antihyper1ipidemic activity. Hypog1ycemic activity s The product prepared from Moringa Oleifera Lam. fruit (Drum stick) is investigated for its hypoglycemic effect in normal Rabbits. The product is found to have no hypoglycemic activity in normal rabbits. The doses studied are 250 mg/kg and 500 mg/kg single dose. The blood glucose levels of human subjects remained unaffected during the study conducted to evaluate hypocholesteromic properties of this product, The subjects had not complained of any weakness or any other symptom normally associated with hypoglycemia. This product in the doses and duration studied has not effected the blood glucose levels. Mechanism of actions The e;;act pharmacological mechanism of action is not yet established. The work is in progress to elucidate the mechanism of action of the product prepared from Moriga Oleifera Lam fruit (Drum stick) for the hypocholesteremic activity. RESULTS: The results are provided in Tables 1 to 8 of the accompanying drawings in which : Table No.1 shows the effect of dried pulp powder prepared from fruit of Moringa Oleifera Lam. on serum lipid of normal rabbit.: Values 3.re of mean + SEM MS denotes not significant P V a 1 u. e s s a ■ Group In Standard laboratory diet given daily for 120 days Group IlsStandard laboratory diet + Lovastatin Group IllsStandard laboratory diet + Moringa. C/P The ratio of cholesterol to Phospholipid LDL ratio s HDL cholestero1/LDL cholestrol AI s atherogenic inde;;. 38 Table? 2 shows the ef"fect of dried pulp powder prepared from fruit of' Moringa Dleifera Lam.on serum lipid of hypercholestrolemic rabbits Values are of mean + SEM NS denotes not significant P.va1ues:a Group I sHypercholesterolemic diet given daily for 120 days Group 11sHypercholesterolemic diet + Lovoastatin Group 111sHypercholesterolemic diet + Moringa C/P The ratio of cholesterol to Phospholipid LDL ratios HDL cholesterol/LDL cholesterol AI:atherogenic index Table No.3. The effect of dried Pulp powder prepared from fruit of Moringa Oleifera Lam. on serum lipid of normal ratabit- In TablH3 3 Column 1 : Total cholestrol in mg/dl; Column 2: HDL cholestrol in mg/dl? Column 3s Triglycerides in mg/dl; Column 4: VLDL in mg/dl; Column 5; LDL mg/dl; Column 6: Phospholipids:mg/dl Column 7: Total proteins in gm%; Column 8: C/P; Column 9; A.I. Group 1 ?.; 3 are compared to group 1 ns not significant P value: a Group IsStandard laboratory diet given daily for 120 days Group 2sSta.ndard laboratory diet + Lovastatin, 6.0 mg/kg/day,, 120 days Group 3:Standard laboratory diet + Product made from Moringa Oleifera Lam 200 mg/kg/day P.O C/P The ratio of cholesterol to Phospholipid LDL ratio: HDL cholesterol/LDL cholesterol Al :atherogenic inde;; Table no.4 The effect of dried Pulp powder prepared from fruit of Moringa Oleifera Lam. on serum lipid of normal rabbit: C,P, T represent Cholestrol , Phospholipids, and Triglycerides expressed as mg/g of v’jet tissue. ‘Values ars of mean j.- 9EM NS denotes not significant P V a 1 u e s ■■:: 0.0 01; ta Group IsStandard laboratory diet given daily for 120 days Group II:Standard laboratory diet + Lovastatin, 6.0 m g . k g / d a y , 12 0 d a y s Group III;Standard laboratory diet + Product made from Moringa Oleifera Lam 200 mg/kg/day P.O,, 120 days Table no 5 The effect of dried Pulp powder prepared from fruit of Moringa Oleifera Lam. on body & organ weight normal rabbit: Values are of mean + SEM NS denotes not significant P.values Group IsStandard laboratory diet given daily for 120 days Group IIsStandard laboratory diet + Lovastatin, 6.0 m g/k g/d a y, 120 d ay s Group IIIsStandard laboratory diet + Product made from Moringa Oleifera Lam 200 mg/kg/day P.O, 120 days 40 Table no 6. The effect of dried Pulp powder prepared from fruit of Moringa Oleifera Lam. on serum lipid of hypercholestrolemic rabbits ‘Values a.re of mean + SEM MS denotes not significant P values; a Group IsHypercholesterolemic diet given daily for 120 days Group 11nHypercholesterolemic diet + Lovastatin 6.0 mg/kg/day 120 days Group III: Hypercholesterolemic diet + Product made from Moringa Oleifera Lam 200 mg/kg/day P.O 120 days C/P The ratio of cholesterol to Phospholipid LDL ratio :HDL cholesterol/LDL cholesterol AI satherogenic inde;; Table no 7 The effect of dried Pulp powder prepared from fruit of Moringa Oleifera Lam. on organ lipid of Hypercholesterolemic rabbit: Groups II and III are compared to Group I ns denotes not significant P v a 1u es 5 a Group IsHypercholesterolemic diet given daily for 120 days Group 11sHypercholesterolemic diet + Lovastatin, 6.0 mg/kg/day, 120 days Group 111sHypercholesterolemic diet + Product made from Moringa Oleifera Lam 200 mg/kg/day P.. 0,120 days 41 «'- U/ 4. V..V i I '.„.' The effect of dried Pulp powder prepared from fruit of Moringa Oleifera Lam,. On Body & Organ weight organ lipid of Hypercholesterolemic rabbit: * Values '3. re of mean •+;. SEM NS denotes not significant P.Va 1ues Group IsHypercholesterolemic diet given daily for 120 days Group 11sHypercholesterolemic diet + Lovastatin, 6.0 mg/kq/day, 120 days Group 111sHypercholesterolemic diet + Product made from Moringa Oleifera Lam 200 mg/kg/day P.O, 120 days HUMAr-4 TRIALS ON DRUG 'Moringa Oleifera Lam. Number of patients =6 Dose of Test Drug =250 mg thrice a day ion of Treatment -■3 months subjects with proven hyperlipidaemia during executive medical check;-! up were selected. They were not having any associated diseases and were not taking any other drugs except the trial drug. The routine life, diet,, and exercise were not altered in the subjects. Individuals were provided 250 mq capsules of the drug were advised to take one capsule three times a day. Their lipid levels were measured before the start of therapy. Individuals were advised to report immediately if they felt any side effects. 42 Resul t.s All the individuals completed the trial. At the end of 3 months, serum lipid profiles were examined. The following table gives the results before and after the drug intake. Before therapy After Therapy TC LDL HDL TG TC LDL HDL. TG Patient 1 250 210 30 220 205 165 30 200 Patient 2 240 200 35 210 210 170 35 190 Patient 3 235 185 35 210 190 160 30 180 Patient 4 265 210 30 220 220 190 30 200 Patient 5 225 170 40 200 ISO 160 30 ISO Patient 6 250 210 30 200 200 170 30 180 Discussion All the trial subjects were found to have hyper1ipidaemia on medical check-up. Without altering their life-style, diet, or eKsrcise, they were administered trial drug in the doses of 250mg three times a day for 3 months. There was significant lowering of serum lipids levels at the end of trial period. No other drugs were administered. Considering the animal experiments, there are sufficient grounds to conclude that drug possesses 1 ipids-lowering properties. The exact mechanism of action is not elucidated or is not evident. There were no side effects reported by any of the patient; probably because it is a fruit and not a chemical. 43 It is also envisaged that suitable (Rhizome). 44 When Moringa Oleifera Lam. is administered together with a combination of one or more plants listed above a varying degree of antihyperlipidaemic activity is observed. The antihyperlipidaemic activity of Moringa Oleifera is potentiated either synergistically or additively when a comtaination of these medicinal plants is administered in various proportions for a varying duration of treatment. The procedures which are used in the preparation of the combination product include extracting the respective plant of medicinal plants listed above and intimately miming with the processed or processed plant parts of Moringa Oleifera. Various modifications and workshop alterations be apparent to those skilled in the art from the aforesaid description, without departing from the nature and the scope of the invention. While the invention has been described and with respect to a particular application it will easily be apparent that the art disclosed herein is applicable to the treatment of other ailments. We Claim: 1. A process for making a composition containing a pharmacologically and or biologically active plant Moringa Oleifera limn extract suitable for administration in a convenient dosage form useful for the treatment of hypercholesterolemia, mixed dyslipidemia, hypertriglyceridemia and other clinical disorders associated with lipoprotein metabolism comprising the steps of : cleaning fruit of the said plant; cooking and cooling for 10 to 20 minutes; drying the said cooked fruit; particulating the said dried fruit and sieving through 60 mesh size; converting a therapeutically effective amount of the particulate matter in a predetermined proportion with or without other biologically active ingredients into a consumable pharmaceutical vehicle, such as a capsule, a tablet, oral liquid and the like . 2. The process as claimed in Claim 1, in which tender or semi ripe fruits are selected for the process. 3. The process as claimed in Claim 1 or Claim 2 , in which the tips at both end of the fruit, typically 2 to 3 cms are cut off before cooking. The process as claimed in any one of Claims 1 to 3 , in which the fruit is cut into pieces about 4 cm long before cooking. The process as claimed in any of Claims 1 to 4 . in which the cooking is done by steaming in a pressure vessel. The process as claimed in any of Claims 1 to 5 , in which the drying is done at prom temperature. The process as claimed in any of Claims 1 to 5 , in which the drying is done at 60 degrees celsius, typically in a an oven. The process as claimed in any of Claims 1 to 7 , in which the cooked fruit either before or after drying is slit open to expose the pulp and seeds and the pulp and seeds are scrapped from the jacket. The process as claimed in any of Claims 1 to 8 , in which the dried mass of fruit is pulverised to obtain particulate matter. . The process as claimed in a\ny of Claims 1 to 9 , in which the particulate matter of Moringa 01 ifera is intimately mixed with therapeutic doses of at least one of plant parts selected from a group containing the following: Aegle marmelos (Fruits:ripe and unripe)? Agave vera- cruz (Roots, Leaves, Gum); Allium cepa (Bulb); Allium Sativum Bulb, (Oil); Aloe darbadnis (Leaves);Bambusa Arundunaceae (Leaves); Boswellia serrata (Gum); Brassica (Oil) ;Cajanu.s cajan (Seeds)jKapparis decidua (Leaves, fruit and stem);Capsicum fruitescens (Fruit); Carum capaticum (Fruits and roots); Celestrus peniculatus (Seed oil, bark, root and fruit); Cicer arietinum (Seeds, leaves); Commiphora mukul (Gum resin); Curcuma amada (Rhizome);Curcuma longa (Rhizome); Cyanopus tetragonoloba (Seed)jEmbelica officinalis (Dried fruit seed, leaves);Embelica ribes Seeds, (fruit and bark);Eugenia cumini (Seeds);Innula recemosa (Root); Juglans regia (kernel,oil); Medicago sativum (Seeds); Momordica charantia (Fruits);Mucuna pruriens (Seeds,fruits,root); Musa Sapientum (Root, stem,flower, fruits,leaves); Nepeta hindostena (Whole plant); Phaseoulus aureus (Seeds); Phaseolus mungu(Seeds); Picrorhiza kurroa (Roat);Piper nigrum (Leaves);Pisum sativum (Seeds); Plantago ovata (Seeds);Pterocarpus marsupium (Gum, leaves); Terminalia arjuna Bark;Sussurea lappa (Root); Thevatia nerifolia Leaves; Trichosanthes dioca (Deseeded fruit powder); Trigonella foenum graecum (Leaves and seeds); and Zingiber officinalis (Rhizome) for conversion into a suitable dosage form.

Full Text

FIELD OF INVENTION
This invention relates to a process for making a composition containing a pharmacologically and/or biologically active plant extract suitable for administration in a convenient dosage form useful for the treatment of hypercholesterolemia, mixed dyslipidemia, hypertriglyceridemia and other clinical disorders associated with lipoprotein metabolism
Particularly, the present invention is directed to provide a composition in a convenient dosage form, useful in restoring and maintaining a satisfactory lipid profile in an animal body, including the human body, and typically having the pharmacotherapeutic activity of increasing high density lipoproteins, and lowering low density lipids and triglycerides.
DESCRIPTION OF THE BACKGROUND ACTIVITY OF THE ART
For utilization and storage of the fat absorbed from the diet and lipids synthesized by the liver and adipose tissue, they have to be transported between the various tissues and organs. Storage and transportation poses a problem since lipids, being nonpolar. Are insoluble in blood plasma, which is typically an aqueous environment. The body solves this problem by combining the hydrophobic lipid moiety with amphipathic lipids such as phospholipids and cholesterol and proteins to form water miscible lipoprotein molecules. In the anabolic phase of their feeding cycle, omnivores, such as humans, ingest excess calories. This phase is followed by

a negative phase in which the animal draws upon its cryohydrate and fat stares. This cycle is mediated by Lipoproteins involved in transporting lipids from the intestines as chylomicrons and from the liver as Density Lipoproteins(VLDL) to the adipose tissue for storage and to the other tissues for oxidation. The final stage in the catabolism of VLDL results in Low density Lipoproteins (LDL) also called Beta-Lipoproteins Also involved in an intermediate stage of VLDL and chylomicron metabolism and cholesterol transport is another lipoprotein known as the alpha-lipoprotein or HDL. In both LDL and HDL, cholesterol and phospholipids airs the predominant lipids. TriacyIglycerol (also known as triglycerides TG) is the predominant lipid moiety in chylomicrons and VLDL. Thus Chy1comicrons transport TG from digestion and absorption of dietary lipids. VLDL transport TG from the liver to the tissues. LDL are cholesterol rich and result from the metabolism of VLDL and act as a mediator and Are involved in depositing cholesterol in the tissues and HDL are cholesterol rich but are involved in removing cholesterol from the tissues to the liver for conversion to bile salts.
Cholesterol plays a major role in the genesis of artherosclerosis of vital arteries and which, when the coronary arteries are involved, may lead to ischaemic heart disease. It must be understood that only half the cholesterol of the body is provided by the average diet. The other half is synthesised within the body itself. All tissues containing nucleated cells are capable of synthesising cholesterol. The liver accounts for 10"/. of this synthesis, the gut 15"/. and the skin almost 20%.

Because of its propensity to dump cholesterol on the arterial walls, LDL has been labelled as the 'bad' cholesterol whereas HDL' because it tends to scrape away cholesterol from the vessels and carry it to the liver has been labelled as the 'good' cholesterol. The role of TG in artherosclerosis is as yet unclear.
Of the serum lipids Cholesterol is most often incriminated as a risk factor in coronary heart disease (CHD). Parameters such as serum TG, VLDL and LDL have also been incriminated. The Framingham study has demonstrated a linear increase in coronary 'risk' with increment of total plasma cholesterol level from ISO mg!*; upwards- a 1'/. fall in cholesterol predicts a 2% reduction in CHD risk. LDL as the carrier of 70% of the total cholesterol to the tissues is the most potential atherogenic agent. On the contrary an inverse relation between CHD and HDL concentration has been found. A raised HDL concentration is beneficial and protective against CHD. This protective mechanism is explained by two mechanisms operating in parallel:
(a)'reverse transport's the scavenging action of HDL by which the intracellular cholesterol content is reduced by HDL transporting Cholesterol to the liver from the tissues for degradation; and
(b)control of TG catabolism. An increase in HDL concentration is associated with a faster elimination of TG and its artherogenic intermediates.
Elevated TG is suggestive of a less effective intravascular lipolysis and hence in the reduced formation of HDL, HDL has shown to competitively inhibit LDL binding an uptake. Thus
4

decreased plasma levels of HDL tend to increase LDL uptake, while increased levels of HDL decrease cellular uptake of JPL. It has na\,-4 been postulated that the ratio of LDL cholesterol and HDL cholesterol is important in predicting the onset of CHD, If the ratio is high the risk is more. To predict a minimal risk of CHD the following determinant readings have been suggested
A total serum cholesterol reading less than 200mg/dl
A serum LDL reading less than 130 mg/dl
A serum HDL reading greater than 35 mg/dl.
A serum TG reading less than 200 mg/dl
Any variance in the above readings in the lipid profile of an individual will require effective ways to modify the profile to achieve the minimal risk parameters prescribed.
The first step to achieve a desired lipid profile is to
resort to dietary and life-style changes ,
Dietary changes include the consumption of less fat,
particularly animal and dairy fat and other saturated fats.
Merely cutting down on dietary cholesterol is not a critical
factor. Eating more soluble fibre, such as oat bran and
generally reducing obesity if present.
Life style changes include moderate aerobic and nonaerobic
exercises, stopping smoking, regulating meal times and
reduction of stress.

If Dietary changes and Life style changes are not have been attempted for a period of six to eight months and have been found to be ineffective, drug therapy is resorted to. If this option is exercised, it is generally tailored to match the particular individual's lipid profile. It is therefore clear that the atherosclerotic process is enhanced by increased blood cholesterol level. The frequent association of ischaemic heart disease with hypercholesterolemia, dyslipidemia has stimulated search for substances which reduce blood cholesterol level. Many such substances were discovered but they 3i.re reported to have adverse side effects and other disadvantages. Hence they could not be advocated for use in daily life. Efforts were made to isolate a promising hypocholesterolaemic agent out of the substances taken in routine diet, leather et al. reported hypocholesterolaemic activity of Cicero anetirium in albino rats and rabbits. Gupta and Mehrotra demonstrated that oral administration of onion lowered the experimentally induced alimentary lipaemia in human beings. Bordia et al. has reported the protective action of garlic and onion in human subjects against fat induced hypercholesterolemia.
Different therapies have been suggested for lowering cholesterol, in general and modifying the lipid profile as a whole. These includes
Niacin 3 This B vitamin is the most effective cholesterol lowering drug. Its cholesterol lowering action is unrelated to its vitamin action. It is required to be consumed in large doses: over 4 to 5 grams per day and over a period of time it raises HDL and is especially useful in lowering TG and LDL.

However it has moderate side effects including severe generalised intense skin flushing,
These drugs can lower LDL but also at the same time lower HDL. Their side effects include gastrointestinal bloating and gas, decreased absorption of fat soluble vitamins
Gemfibrozi1; It has modest effects on LDL but is effective in lowering TGH and raising HDL. Side effects include abdominal and epigastric pain, nausea and vomiting, known interaction with anticoagulants,
HRT; Hormone replacement therapy can raise HDL and lower LDL but the side effects include a risk of breast cancer. Plants halving pharmacological and biological activity have been the basis of treatment of human diseases for centuries. Use of pharmacologically or biologically active plant extracts is well-known. It is also known that the biologically or pharmacologically active compounds can be isolated and purified from the plant extract to obtain therapeutic compositions.

There are reasons to believe that plant extracts having pharmacologically and biological activity can serve as a good source of lipid profile modifying agents.
It is suggested that the plant extract identified in the present invention will provide short and long term benefits to patients having clinical disorders associated with Lipoprotein metabolism and an undesirable Lipid profile with the concomitant lowered risk of CHD and artherosclerosis as a result of its lipid profile modulating activity and other supportive activity.
The drugs used at present have limited advantages and their effects are mainly of short term duration and there are many disadvantages in the use of these drugs over extended periods of time. Further the drugs used at present are costly and have low benefit-risk ratio. The ideal compound to modify the progress of the disease has not yet been found hitherto fore.
This invention therefore specifically relates to a plant
extract composition for the treatment of
hypercholesterolemia, mixed dyslipidemia,
hypertriglyceridemia and other clinical disorders associated with lipoprotein metabolism.

OBJECTS OF THE PRESENT INVENTION
A further object of this invention is to provide a composition aforesaid that acts without exerting toxic or side effects.
Still another object of this invention is to provide a disease-specific synergistic composition, in convenient dosage form.
A further object of the invention is to provide a method of treatment of clinical disorders associated with lipoprotein metabolism, elevated undesirable cholesterol levels and specifically hypercholesterolemia,mixed dyslipidemia and hypertriglyceridemia, - a method which, unlike present available treatment which usually have severe side effects, demonstrates little in the way of side effects.
SUMMARY OF THE INVENTION
According to this invention there is provided a method of treating clinical disorders associated with lipoprotein metabolism, elevated undesirable cholesterol levels and specifically hypercholesterolemia,mixed dyslipidemia, and hypertriglyceridemia, in an animal, typically a human, comprising administering to the animal, typically enterally, in a convenient dosage form, a therapeutically effective amount of the extract of the plant in a predetermined proportion with or without other biologically active inorganic ingredients .

In accordance with this invention there is provided a process for making a composition containing a pharmacologically and/or biologically active plant extract suitable for administration in a convenient dosage form useful for the treatment of hypercholesterolemia, mixed dyslipidemia, hypertriglyceridemia and other clinical disorders associated with lipoprotein metabolism comprising the steps of :
cleaning fruit of the plant Moringa Oliver limn;
cooking and cooling for 10 to 20 minutes;
drying the cooked fruit;
articulating the dried fruit and sieving through 60
mesh size;
converting a therapeutically effective amount of the
particulate matter in a predetermined proportion
with or without other biologically active
ingredients into a consumable pharmaceutical
vehicle, such as a capsule a tablet , oral liquid
and the like .
Typically the process a step in which tender or semi ripe fruits are selected for the process and tips at both end, typically 2 to 3 cms are cut off before cooking. Further , the fruit is cut into pieces about 4 cm long before cooking done by steaming in a pressure vessel.
Drying is done at room temperature or at 60 degrees celsius, typically in a an oven. Typically, the oven may be of the forced hot air type , the steam jacketed type or the

electrically heated type oven. The cooked fruit either before or after drying is slit open to expose the pulp and seeds and the pulp and seeds are scrapped from the jacket and the dried mass of pulp and seeds is pulverized to obtain particulated matter which is sieved through a 60 mesh sieve. The powder so obtained is then converted into a. pharmaceutical dosage form in a conventional manner.
DETAILED DESCRIPTION
The invention provides a method of treating clinical disorders associated with lipoprotein metabolism, elevated undesirable cholesterol levels and specifically hypercholesterolemia,dyslipidemia, and hypertriglyceridemia, in an animal, typically a human, comprising administering to the animal, typically enterally, in a convenient dosage form, a therapeutically effective amount of the extracts of the plant Moringa Oleifera Linn in a predetermined proportion with or without other biologically active inorganic ingredients the said composition made in accordance with a novel process which is hereinafter disclosed.
Habitat„-A beautiful tree(plant) in the sub-Himalayan range and commonly cultivated in India and Burma. It is a very popular backyard tree that grows over nine meters tall. It has a soft white corky trunk and branches bearing a gummy bark. The leaves are trippnately compound bearing several small leaflets. The flowers are white. The long slender fruit is a many seeded pod in the shape of a 'drumstick' and the seeds are three winged. Propagation is by wind. The flowers, Itender leaves and fruit pods are eaten as a vegetable or made into a pickle.

Parts Used,-

Carbohydrate 14 g. Vitamin A 11, .235 I.U.
Protein b g ■ Vitamin B2 59 meg,
Fat O g- Niacin 0,7 mg ,
Calcium 425 mg. Vitamin C 217 mg.
Phosphorus 70 mg, Digesting T ime 2 Hrs.
Iron 7 mg, CALORIES 84
constitution: Hot and Dry 3, Physiopharmacology and Therapeutics
Moringa or Horse radish tree grows all over India and Pakistan. It is beautiful tree mostly grown as a backyard tree in most of the South Indian homes for its drum-stick like fruits, tasty flowers and the leaves that are cooked and eaten as vegetable. Leaves
Moringa leaves are not very popular as market vegetable, because majority of us think that the leaves are hot and not nutritive but the chemical analysis of the leaves shows that Almighty God has treasured enormous nutritive wealth in these cheap and discarded leaves. Fresh juice of the leaves supplies the following vitamins and minerals having comparative value of other foods: Vitamin A
Fresh juice 1 cup full supplies as much vitamin A as one gets by eating any one of the following foods:
eggs 9 Mutton 16 kg.
Sheep's liver 50 g. Butter 500 g.
Shelled almonds 1 cupful Fresh Cow's milk 80 cups.

Vitamin C Equal to:
Oranges 6 Limes 6
Apples 8 Mangoes 20
Bananas 16 (Langra Variety) 3
Grapes 2„5kg. Water melon 7.5kg.
Calcium
A handful of fresh leaves supply as much calcium as one gets by eating any one of these foods:
Almonds 900g. Chicken roast 3kg.
Oranges 8 Eggs(hen's) 20
Papaya 3.5kg. Mutton chops 2.5kg,etc
Drum-stick leaves are a rich source of all the essential amino acids. Young leaves are used as food. Leaves ground into a paste with a few pods of garlic, a. bit turmeric, salt and pepper are given internally in scurvy, catarhal affections, and in cases of dog-bite are applied externally over the bite. In 5 to 6 days the wound will heal, the inflammation and the febrile symptoms subsiding. Leaf-juice is dropped into the eyes in fainting fits due to nervous debility, spasmodic affections of the bowels, hysteria, flatulence etc; mixed with honey it is applied as ajar to the eyelids in eye diseases. A quarter seer of leaf-juice mixed with one toga of saindhava is given in excessive urinary secretions. In cases of headache the juice of leaves with black pepper rubbed tin to it is applied warm to the aching parts. Leaf-juice in doses of 4 tolas is given as an emetic. Poultice of the leaves is useful in reducing glandular swellings. It always produces a blister . It is estimated that lOOg.of the leaves contain the following concentration in grammes.

DRUM STICK LEAVES
Arginine 6
Histidine 2.1
Isoleucine 6.3
Leucine 9.3
Lysine 7.6
Methionine 2

Phenylalanine Thereonine Tryptophan Valine

6.4 4.9 1.9 7.1

A glassful of durm stick leaves-soup supplies as much protein as one gets by eating any one of the following foods approximately:
Beef lOOg. Fish 120g.
Chicken lOOg. Pork lOlg.
Milk 2.5cups Eggs 2
Soup of the leaves prepared by immersing a handful of tender leaves in boiling water 6 02.for 5 minutes with a lid on the vessel and after this period the vessel is immersed in cold water so as to cool the soup quickly. To this soup a pinch of salt, pepper, lime juice half teaspoon is added and drunk every morning as a tonic medicine to get protection against, malnutrition, anaemias, tuberculosis, asthma, seasonal attacks of colds and bronchitis, pre-mature oldage,pre-mature loss of strength and vigour,nervousness, functional sterility in ma1es and fema1es, etc.
A teaspoon of fresh-leaf juice mixed with honey and a glassful of tender coconut water, is given two to three times as a herbal medicine during the treatment of cho 163ra,dysentery ,diarrhoea, colitis, jaundice,etc.

A cupful of the fresh leaf-juice coagulated by heating it gently on water bath, and then the clear fluid is filtered. It is mixed with milk instead of water and the infants and children are fed once day to help them grow healthy with strong bones, pure blood and develop high resistance against infection and malnutrition.
The same tonic-medicine can be regularly used during all times by all irrespective of age. Its regular use during pregnancy and lactation, helps the mother to get extra calcium,iron,vitamins at no cost and also helps the healthy development of the baby with strong nerves and bones. It acts on the uterine contracting mechanism and prevents sluggishness of uterus which we call Uterine Inertia and eases child birth reducing severe blood loss and post-partum complications.Its regular use after child birth increases breast milk and helps the mother to recover quickly from lying-in-period.A tablespoon of coagulated fresh leaf-juice mixed with a glass of fresh-juice of cucumber or carrot is an effective medicine for scanty urination, constant burning in urethra due to high acidity of urine,myxoedema,toxaemias of pregnancy,dropsy due to heart,liver,kidney disorders, hypertension, excessive thirst due to summer heat, diabetes, constipation,etc. A teaspoonful of the juice with Rock-salt 10 g,once daily is used to cure excessive’ urination of non-diabetics. Fresh juice 1 tablespoonful with honey,taken every night before going to bed cures; night blindness,weak memory,loss of smelling power,poor hearing etc. Taken with lime juice
cures vert igo, b 1 eed.i nn ni1f2rlinn frnm 1iinn=r, AHH

nose, hiccough., biliousness, indigestion, morning sickness,malabsorption syndrome etc.
A teaspoon of the fresh juice with salt is given as an emetic to weak persons and children suffering from excessive gas. A teaspoon of ghee prepared by clarifying with fresh leaves as handful per blob butter is given as a tonic for children.
Fresh leaf-juice is instilled in the eyes to cure fainting fits due to nervous debility corneal ulcers,burning and itching in eyes, flickering and twitching of the eye lids, failling of the eye lashes, night blindness due to vitamin A deficiency etc. Juice is instilled in the nose to cur syncope ( E’havaprakash 3 .
Leaf juice mi;ced with equal quantity of radish-leaf juice is applied over piles with gratifying results. Juice mi;;ed with til oil and heated to evaporate the watery content and the oil is applied as a medicine to cure scabies, rheumatism, sprains and contusions. Roasted leaves are: fomented to reduce pain and inflamation caused by injuries, and to reduce the water content of hydrocele.
Fresh leaf juice with a pinch of turmeric powder is applied to extract guinea worm. As a first aid dressing in dog bite, leaves Slurs pounded, with few cloves of garlic and a pinch of turmeric; the wound is cleaned vita0 pre-boiled water and the mixture is applied. (It must be remembered that dog bite causes serious complications such as tetanus even if the

dog is not rabid. If bitten by a mad dog,, rabies is sure to develop, therefore, all dog bites must be treated carefully with a full course of 7 to 15 Anti-Rabies-injections that are given free in all the Govt.dispensaries and hospitals.)
Fresh leaf juice applied with lime juice cures pimples, black heads and keeps one's face flower fresh. A teaspoonful of the fresh leaf juice mixed with 3 peppers is applied over temples to cure head-ache. An ounce of the fresh leaf-juice acts as a safe emetic in chronic bronchitis, asthma etc.(for adults only). Poultice of the fresh leaves is applied over glandular swellings. It reduces pain due to its counterirritant action (Allowing the poultice for a long time causes blisters.) Fruits: Green coloured elongate fruits with striations and multipoded seeds, length 30-45 cms and diameter 1-2 cms Fruits like long sticks are nutritive aphrodisiac. They 3.re cut into desired pieces and cooked as vegetable are usually eaten during their harvest time in summer. Soup of the tender pods have been used as a medicine for rheumatism, colds, impotency, small urinary stones, weakness of the nerves, enlargement of liver and spleen, constipation etc. Regular use of the pods prevents the infection from round and pin worms. Soup mixed with honey is given as a food-medicine for paralysis,Bel 1's Palsy Jhemiparesis etc. It rectifies the menstrual irregularities. Pickles of the raw fruits prepared with pure vinegar is useful in curing lumbago,sciatica.

paralytic stiffness of the limbs,, rheumatism etc. Eating the fruits cooked with unripe mango, reduces summer heat in the body and prevents iron and vitamin C deficiency,
"The pods (fruits) made into a soup are prescribed by Hakims as a diet in sub-acute cases of enlarged liver and spleen" I, particular pains, tetanus, debility of nerves, paralysis, pustules, patches,leprosy etc. Young, unripe pods, known as drum sticks, area favourite ingredient in curries, and they act as a peventive against intestinal worms. Seeds of the pods ground with water and instilled into the nostrils cure headaches due to cold and excess of K'afa. They 3.re given in cases of ascites resulting from enlargement of the liver and spleen. :
Nutritive value of Drumstick ( Moringa Oleifera fruit)
Ed i b1e portion: 83%
Moistures 86.9X
Proteins 2.5"/.
Fat; O.iy.
Minerals 2.0%
Fiber 4.8%
m d rates; 3.7%
calories 26 per lOOg of edible portion
Flowers
Flowers Are hot and dry in constitution. They are cooked
and use as vegetable. Flowers boiled in milk and re used
as a se;;-tonic to cure impotency in young persons.
Fresh juice of the flowers 1 tablespoon with butter milk
one glass is given as a medicine to cure asthmatic attacks,

scanty urination, indigestion, gravel in bladder. Juice given twice with tender cocoanut water acts as a diuretic tonic-medicine during the treatment of nephritis, congestive heart failure, urethritis, cystitis,
Flowers or leaves soaked in vinegar are used with food or they 3.re made into curries which are very wholesome. Bark: The corky-bark is grey and is about an inch thick. It is acrid with pungent taste and yields a coarse fibre. Bark contains a white crystalline alkaloid(occurring in the spirituous extract), 2 re5ins(one soluble and the other (insoluble in ammonia), an inorganic acid,mucilage(gum) and ash S p.Cn Bark of the stem and the roots used in Omani and Ayurvedic medicine for various ailments. Col.R.N.Chopra and De analysed the chemical contents of the bark and they found the following chemicals:
Myristic acid 7,3 per cent Oleic acid 7.3 per cent Palmitic acid 10.8 per cent Lignoceric acid 3 per cent Behenic acid 8.9 per cent Phytester1 9 per cent Stearic acid 10.8 per cent
The scientists, also extracted various useful alkaloids such as: the platinic chloride having yellow rectangular plates with melting point 221 and the picrate having yellow wooly needles with 195 melting point.
The pharmacological action and therapeutic uses of these alkaloids prepared from the bark of Moringa P. were also clinically tested at Calcutta Tropical School. The resea,rchers confirmed that the crystalline bases have no marked physiological action, whereas the Amorphous base.

sympathetic nerve endings of the entire human nervous net. By its stimulating action, it constricts the blood vessels and elevates the blood pressure, accelerates heart-beat. Its main action on the heart is due to direct stimulation of cardiac sympathetic nerves, but the myocardium may be slightly affected. The researches also observed that the amorphous base inhibits the tone and the movements the involuntary muscles of the gastrointestinal tract and bronchioles. The stimulant action of this base was also found in other organs. It produces slight diuresis, dilates pupils and is destroyed in the liver. Large doses of this base produce depression in voso-motor nerve endings. However, its sympathomimatic action cannot be compared to Adrenaline,
Considering the facts of the above research the powder of the dry bark 4 ounces is boiled in a pint of water for about half an hour and an ounce with a teaspoonful of honey taken three times daily after food for a month cures impotency, pre-mature ejaculation, thinness of semen, scanty menstruation in young anaemic girls, asthma, bronchitis, with severe cough,scurvy,etc.
The bark 1 oz. is boiled with a handful of tender bamboo shoots in 18 ounces of water until 8 ounces remain. This decoction 2 ounces taken four hourly for 2 days acts as an abortifacient. An inch long piece of bark boiled and trimed to make as a pessary is inserted in the os to induce abortion in folk medicine (such attempts in lay hands

causes grave risks). Rouring warm decoction of the bark over paralytic limbs improves blood circulation and reduces stiffness.
A handful of the fresh bark is pounded and in or coconut oil 12 ounces Mustard seed 1 tablespoon and bailed till the bark begins to turn brown, later the oil is cooled strained and preserved in a bottle. It is applied as an analgesic liniment in painful conditions of the joints, due to rheumatism, sprains, ritis,etc. Few drops of the oil mi;!ed with some plain coconut oil is applied over the scalp to lengthen hair and prevent hairfall.
A hole is made in the stem of the tree and a full cut circular betel nut is inserted and the hole is closed with wheat flour paste to keep it secure. After 2 months, the nut is taken from the stem and preserved.
A piece of it if held under the tongue during intercourse prevents pre-mature ejaculation. The absorption of lignoceric acid in the circulation acts on the time mechanism of semen ejaculation and helps in delaying the passing of ejaculatory transmission.
Warm juice of the stem bark 5 drops is put in the ear to stop ear ache due to exposure to breeze.
In Efengal half-ounce doses of the bark are said to be used to procure abortion.

Root
Root of durm stick tree resembles like European Horse-radish in smell and appearance. Its bark is pungent and has more medicinal value than the bark of the stem. Root yields an essential oil very pungent and offensive in odor.
Decoction or the tincture of the root bark prepared by adding equal parts of orange peel with a pounded nutmeg is given half to 1 teaspoon thrice daily after meals as a carminative medicine in spasmodic conditions of bowels, flatulence. In hysteria, dizziness, nervous debility, the same may be used with good results.3 Decoction of the roots mixed with pepper 2, garlic 3 cloves and honey is given an ounce thrice daily as medicine for intermittent fever, malaria, epilepsy, gout, dyspepsia, flatulent colic,ascitis enlargement of liver and spleen etc.2,4,5.
In soreness of the mouth, decoction of the roots is gargled. In carried tooth, finely powdered root is filled. It must be noted that once the hard enamel of the tooth is damaged, it is not possible to regenerate it again Therefore, to get permanent relief, one is advised either the tooth be filled or extracted.
Decoction of the fresh rootd in 20) taken an ounce thrice daily for a month along with cardamom 1, before food, cures hiccough, hysteria, lumbago, rheumatoid arthritis, etc,4 Taken with honey once at 6 p.m., and another dose at 10 p.m.,cut shorts the severity of asthmatic attacks 5.

Regular use of the decoction(1:20) 1 ounce thrice daily with Asafoetida 2 grs. is said to cause abortion in early pregnancy. (In my opinion, it may not be useful in genuine pregnancy, taut may tae used in delayed menstruation due to lack of progestrone, primary amenorrhoea and uterine inertia).
Fresh Juice boiled in water and a little salt is added to this decoction, is gargled in sore-throat, relaxed uvula, pharyngitis, hoarseness of the throat etc. Paste of the roots mixed with a teaspoonful of seed is applied as a very useful liniment to cure rheumatic pains, inflamatory swellings and tumours, paralytic parts, sprains, dislocations etc. Fresh juice 5 drops is put in ears to cure BAr ache2. Paste of roots prepared with water is applied over scabies, ringworm, itching of the skin due to its dryness etc.
Seeds
Dry seeds of moringa are nutritive and contain a very-useful commercial oil known as Ben oil. The husked seeds yield "on simple pressure a clear, limpid, almost colourless, rather thick at ordinary temperature" fixed oil 36.6 p.c, known as Beni or Ben or Moringo oil. It contains 60 p.c. of liquid oil and 40 p.c. of white solid fat. European grated horse-radish contains sulphur.
24

It contains Myristic acid 7.3 per cent, Palmitic acid 4.2 per cent. Oleic acid 65.8 per cent, Stearic acid 10.8 per cent,, Behenic acid 8.9 per cent and Lignoceric acid 3 per cent. 9 per cent of Phytoserol in the oil. The oil contains about 3.7 per cent unsaponifiable matter.
Ben oil is a clear liquid which is rather thick at room temperature. Its specific gravity is 0.912 to 0.915 at 60F. It has not taste and smell. It does not turn rancid and saponifies very slowly. Therefore, it is an ideal medium for lubricating delicate machine parts like watches, cameras,, etc. Perfumers esteem the oil for its great power of absorbing and retaining even the most elusive odours.
Ben oil mixed with ground-nut oil is used externally with very gratifying results in the treatment of rheumatism, gout etc. The oil is found to be a good source of a Behenic acid in nature; Behenic acid was synthesised from n-cicosanic acid, and also by the hydrogenation of methyl eru.cate and finally hydrolysing the resulting methyl behenate„-( V.C.Parekh, Indian Institute of Scie’nce, Bangalore)
Paste of the dry seed is applied in the vagina half an hour before conjugal union to increase the voluptuous feelings in both the partners. It acts as a safe contraceptive if used with little salt and honey and inserted along with a tampon before sexual intercourse. Seeds of the fresh pods
25

head-ache due to coldB. Paste of
fenugreek infusion and honey is given thrice daily for a month to cure ascitis caused by liver derangement. Paste of the seeds is applied over glandular swellings.
Gum
Gum of moringa is opaque and white when it first comes from the trunk, but soon becomes pinkish dark on exposure to air. It is bland and nucilaginous and becomes friable in dry air and is tough in damp air. It holds 20 per cent of its weight of water. The gum is insoluble in water. The amount of bases present in the alkaloid are very small and its practical utility in therapeutics is doubtful unless the quantity of active principles is increased by suitable cultivation.
Gum is used as a medicine to cure spermatorrhoeaj excessive menstruation in anaemic girls2, etc. Usually about 20 gr. of the gum is fried in ghee and is used with sugar and milk for the above said complainst. Fried gum is also used to cure flatulence, head ache. Fresh liquid like gum mixed lime juice is applied over painful conditions of the joints, glandular swellings, etc. Boiled with castor oil is used as an analgesic medicated oil in rheumatism paralysis,neuritis etc2. Gum mixed in til oil is put in ears to alleviate ear ache. Mixed with milk gum is rubbed to cure head ache, arthritis, butaos, painful bones in syphilis. Gum is inserted in the external os to cause abortion.
26

'usting with DuD.T. powder over the tree prevents the reeding of hair caterpillars, that the commonly found on he stem. Touching them causes serious allergy and contact esuratitis. These worms thrive well on the sap of the tern bark and leaves.
General Action.-Antispasmodic, stimulant, eKpectorant, and diuretic. Fresh root is acrid and vesicant5(has the taste of horse-radish); internally stimulant, diuretic and antilithic. Gum is bland and mucilaginous seeds are acrid and stimulant. Bark is emmenagogue and even abortifacient. Flowers .’re stimulant, tonic and diuretic and useful to increase the flow of bile. Mahomedan Writers describe the flowers as hot and dry. The plant is acardiac and circulatory tonic and antiseptic.
Pharmacological Action-"The pharmacological action of the vegetable bases isolated from M.pterygosperma worked out by Chopra ?■; De:-"The crystalline base has little or no physiological action, whereas the amorphous base shows marked activity and closely resembles adrenaline and ephed rine in its effects. This base thus belongs to the sympathominetic group of bases. It acts on the sympathetic nerve edings all over the body producing a rise of blood pressure, acceleration of heart-beat and constriction of the blod vessels. Its effect on the heart is mainly through the sympathetic though the myocardium may also be slightly stimulated. It also inhibits the tone and movements of the involuntary muscle of the qastro-intestinal tract and the bronchioles. The effects

sympathetic stimulation i-gere also found in the action of this base on other organs. It produces slight diuresis on intravenous injection in animals, dilates pupils and is detoKicated by the liver.. ‘Jery large doses depress the vasomotor nerve-enmdings» This base differs from adrenaline in that it produces littbe or no rise of blood pres£?ure after ergotoxina, whereas adrenalne produces a fall under similar conditions. The sympathomimetic base isolated from M.pterygosperma is, however, very much weaker in its action than adrenaline or ephedrine.
Action H: Users in Ayurveda and Siddha-Mathura Katu, Kashaya, rasam, Ushna veeryam, Katu-vipakam;
Bark.-Emmenagogue. Seeds.-Aphrodisiac; Flowers.-leaves and root:-Anthelmintic,giddiness,nausea, pitta diseases, astthi Jwaram,T„B.-(Therapeutic Notes).
Action &. Uses in Unani.- Murakab-ul-khuva :-la;::ative, anti-spasmodic; leaves external-laryngitis.-(Therapeutic Notes).
Usess.-Leaves, flowers, immature capsules and root 3.rB eaten as vegetables in curries. Grated horse-radish (European) eaten at frequent intervals during the day and slo at meals will banish the distressing cough that lingers after influenza. As it contains sulphur, it is recommended for rheumatism, ascites and venomous bites; applied as a poultice for neuralgia of he face. Root of the drumstick tree resembles in odour and appearancce that of horse-radish of Europe, for which its is said to be a perfect substitute. A compound spirit made in the usual way of equal parts of Morinaa root and oranqe peel with a

and heat the plate at 120 degree C for 5 minutes, A
Yellowish brown spot with Rf value of 0,.i>2 will be visible
which is comparable with that spot obtained with Working
standard.
Dosage forms:
The dried pulp bulk prepared from Moringa Oleifera Lam, fruit (Drum stick) is used to prepare various dosage forms. Each formulation had 100 mg to 500 mg of the dried pulp bulk prepared from Moringa Oleifera Lam per unit dose.
Capsules:
The dried pulp bulk is sufficiently free flowing for hard gelatin capsule formulation. However, different excipients like Lactose, Starch, Talcum, Magnesium Btearate Etc., in suitable proportions 3.re also employed for facilitating the capsules preparation.
Tablets s
The dried pulp bulk is used in conjunction with different
conventional excipients in compressing into tablet dosage
form. For this purpose bath wet and dry granulation is
employed. These tablets have good disintegrating
properties, meets with the other parameters of tablet
evaluation like hardness, friability, etc.
36

Oral Liquids;
The dried pu1p buIk is used in formu1ation of oral liquids.
li The dried pulp bulk is suspended in a syrupy base with
suitable preservatives yielding a homogeneous suspension.
2. The dried pulp bulk is suspended in a non-syrupy base with suitable preservatives yielding a homogeneous suspension.
3. The dried pulp bulk is prepared into Dry Syrup with suita\ble preservatives. When constituted yields a homogeneous suspension.
OTHERS
Dosage forms which Bre also envisaged under this invention includesRectal suppositoriesj Injectable formulations like intramuscular, intravenous preparations, Effervescent tablets.
Pharmacological Activity discovered:
Hypocholesterolemic and Antihyper1ipidemic activity.
Hypog1ycemic activity s
The product prepared from Moringa Oleifera Lam. fruit (Drum
stick) is investigated for its hypoglycemic effect in normal
Rabbits. The product is found to have no hypoglycemic
activity in normal rabbits. The doses studied are 250 mg/kg
and 500 mg/kg single dose.

The blood glucose levels of human subjects remained unaffected during the study conducted to evaluate hypocholesteromic properties of this product, The subjects had not complained of any weakness or any other symptom normally associated with hypoglycemia. This product in the doses and duration studied has not effected the blood glucose levels.
Mechanism of actions
The e;;act pharmacological mechanism of action is not yet established. The work is in progress to elucidate the mechanism of action of the product prepared from Moriga Oleifera Lam fruit (Drum stick) for the hypocholesteremic activity.
RESULTS: The results are provided in Tables 1 to 8 of the
accompanying drawings in which :
Table No.1 shows the effect of dried pulp powder prepared
from fruit of Moringa Oleifera Lam. on serum lipid of normal
rabbit.:
* Values 3.re of mean + SEM
MS denotes not significant
P V a 1 u. e s s a ■ Group In Standard laboratory diet given daily for 120 days
Group IlsStandard laboratory diet + Lovastatin
Group IllsStandard laboratory diet + Moringa.
C/P The ratio of cholesterol to Phospholipid
LDL ratio s HDL cholestero1/LDL cholestrol
AI s atherogenic inde;;.
38

Table? 2
shows the ef"fect of dried pulp powder prepared from fruit
of' Moringa Dleifera Lam.on serum lipid of
hypercholestrolemic rabbits *Values are of mean + SEM
NS denotes not significant
P.va1ues:a Group I sHypercholesterolemic diet given daily for 120 days
Group 11sHypercholesterolemic diet + Lovoastatin
Group 111sHypercholesterolemic diet + Moringa
C/P The ratio of cholesterol to Phospholipid
LDL ratios HDL cholesterol/LDL cholesterol
AI:atherogenic index
Table No.3.
The effect of dried Pulp powder prepared from fruit of
Moringa Oleifera Lam. on serum lipid of normal ratabit-
In TablH3 3 Column 1 : Total cholestrol in mg/dl; Column 2:
HDL cholestrol in mg/dl? Column 3s Triglycerides in mg/dl;
Column 4: VLDL in mg/dl; Column 5; LDL mg/dl; Column 6:
Phospholipids:mg/dl Column 7: Total proteins in gm%; Column
8: C/P; Column 9; A.I.
Group 1 ?.; 3 are compared to group 1
ns not significant P value: a Group IsStandard laboratory diet given daily for 120 days
Group 2sSta.ndard laboratory diet + Lovastatin, 6.0
mg/kg/day,, 120 days

Group 3:Standard laboratory diet + Product made from Moringa Oleifera Lam 200 mg/kg/day P.O
C/P The ratio of cholesterol to Phospholipid LDL ratio: HDL cholesterol/LDL cholesterol Al :atherogenic inde;;
Table no.4
The effect of dried Pulp powder prepared from fruit of
Moringa Oleifera Lam. on serum lipid of normal rabbit:
C,P, T represent Cholestrol , Phospholipids, and
Triglycerides expressed as mg/g of v’jet tissue.
‘Values ars of mean j.- 9EM NS denotes not significant
P V a 1 u e s ■■:: 0.0 01; ta Group IsStandard laboratory diet given daily for 120 days
Group II:Standard laboratory diet + Lovastatin, 6.0
m g . k g / d a y , 12 0 d a y s
Group III;Standard laboratory diet + Product made from
Moringa Oleifera Lam 200 mg/kg/day P.O,, 120 days
Table no 5
The effect of dried Pulp powder prepared from fruit of
Moringa Oleifera Lam. on body & organ weight normal rabbit:
*Values are of mean + SEM
NS denotes not significant
P.values Group IsStandard laboratory diet given daily for 120 days
Group IIsStandard laboratory diet + Lovastatin, 6.0
m g/k g/d a y, 120 d ay s
Group IIIsStandard laboratory diet + Product made from
Moringa Oleifera Lam 200 mg/kg/day
P.O, 120 days
40

Table no 6.
The effect of dried Pulp powder prepared from fruit of
Moringa Oleifera Lam. on serum lipid of hypercholestrolemic
rabbits
‘Values a.re of mean + SEM MS denotes not significant
P values; a Group IsHypercholesterolemic diet given daily for 120 days
Group 11nHypercholesterolemic diet + Lovastatin 6.0
mg/kg/day 120 days
Group III: Hypercholesterolemic diet + Product made from
Moringa Oleifera Lam 200 mg/kg/day P.O 120 days
C/P The ratio of cholesterol to Phospholipid
LDL ratio :HDL cholesterol/LDL cholesterol
AI satherogenic inde;;
Table no 7
The effect of dried Pulp powder prepared from fruit of
Moringa Oleifera Lam. on organ lipid of
Hypercholesterolemic rabbit:
Groups II and III are compared to Group I
ns denotes not significant
P v a 1u es 5 a Group IsHypercholesterolemic diet given daily for 120 days
Group 11sHypercholesterolemic diet + Lovastatin, 6.0
mg/kg/day, 120 days
Group 111sHypercholesterolemic diet + Product made from
Moringa Oleifera Lam 200 mg/kg/day
P.. 0,120 days
41

«'- U/ 4. V..V i I '.„.'
The effect of dried Pulp powder prepared from fruit of
Moringa Oleifera Lam,. On Body & Organ weight organ lipid of
Hypercholesterolemic rabbit:
* Values '3. re of mean •+;. SEM
NS denotes not significant
P.Va 1ues Group IsHypercholesterolemic diet given daily for 120 days
Group 11sHypercholesterolemic diet + Lovastatin, 6.0
mg/kq/day, 120 days
Group 111sHypercholesterolemic diet + Product made from
Moringa Oleifera Lam 200 mg/kg/day
P.O, 120 days
HUMAr-4 TRIALS ON DRUG 'Moringa Oleifera Lam. Number of patients =6
Dose of Test Drug =250 mg thrice a day
ion of Treatment -■3 months
subjects with proven hyperlipidaemia during executive medical check;-! up were selected. They were not having any associated diseases and were not taking any other drugs except the trial drug. The routine life, diet,, and exercise were not altered in the subjects.
Individuals were provided 250 mq capsules of the drug were advised to take one capsule three times a day. Their lipid levels were measured before the start of therapy. Individuals were advised to report immediately if they felt any side effects.
42

Resul t.s
All the individuals completed the trial. At the end of 3 months, serum lipid profiles were examined. The following table gives the results before and after the drug intake.
Before therapy After Therapy
TC LDL HDL TG TC LDL HDL. TG Patient 1 250 210 30 220 205 165 30 200 Patient 2 240 200 35 210 210 170 35 190 Patient 3 235 185 35 210 190 160 30 180 Patient 4 265 210 30 220 220 190 30 200 Patient 5 225 170 40 200 ISO 160 30 ISO Patient 6 250 210 30 200 200 170 30 180 Discussion
All the trial subjects were found to have hyper1ipidaemia on medical check-up. Without altering their life-style, diet, or eKsrcise, they were administered trial drug in the doses of 250mg three times a day for 3 months. There was significant lowering of serum lipids levels at the end of trial period. No other drugs were administered. Considering the animal experiments, there are sufficient grounds to conclude that drug possesses 1 ipids-lowering properties. The exact mechanism of action is not elucidated or is not evident. There were no side effects reported by any of the patient; probably because it is a fruit and not a chemical.
43

It is also envisaged that suitable (Rhizome).
44

When Moringa Oleifera Lam. is administered together with a combination of one or more plants listed above a varying degree of antihyperlipidaemic activity is observed.
The antihyperlipidaemic activity of Moringa Oleifera is potentiated either synergistically or additively when a comtaination of these medicinal plants is administered in various proportions for a varying duration of treatment.
The procedures which are used in the preparation of the combination product include extracting the respective plant of medicinal plants listed above and intimately miming with the processed or processed plant parts of Moringa Oleifera.
Various modifications and workshop alterations be apparent to those skilled in the art from the aforesaid description, without departing from the nature and the scope of the invention. While the invention has been described and with respect to a particular application it will easily be apparent that the art disclosed herein is applicable to the treatment of other ailments.

We Claim:
1. A process for making a composition containing a
pharmacologically and or biologically active plant
Moringa Oleifera limn extract suitable for administration
in a convenient dosage form useful for the treatment of
hypercholesterolemia, mixed dyslipidemia,
hypertriglyceridemia and other clinical disorders
associated with lipoprotein metabolism comprising the
steps of :
cleaning fruit of the said plant;
cooking and cooling for 10 to 20 minutes;
drying the said cooked fruit;
particulating the said dried fruit and sieving
through 60 mesh size;
converting a therapeutically effective amount of the
particulate matter in a predetermined proportion
with or without other biologically active
ingredients into a consumable pharmaceutical
vehicle, such as a capsule, a tablet, oral liquid
and the like .
2. The process as claimed in Claim 1, in which tender or semi ripe fruits are selected for the process.
3. The process as claimed in Claim 1 or Claim 2 , in which the tips at both end of the fruit, typically 2 to 3 cms are cut off before cooking.

The process as claimed in any one of Claims 1 to 3 , in which the fruit is cut into pieces about 4 cm long before cooking.
The process as claimed in any of Claims 1 to 4 . in which the cooking is done by steaming in a pressure vessel.
The process as claimed in any of Claims 1 to 5 , in which the drying is done at prom temperature.
The process as claimed in any of Claims 1 to 5 , in which the drying is done at 60 degrees celsius, typically in a an oven.
The process as claimed in any of Claims 1 to 7 , in which the cooked fruit either before or after drying is slit open to expose the pulp and seeds and the pulp and seeds are scrapped from the jacket.
The process as claimed in any of Claims 1 to 8 , in which the dried mass of fruit is pulverised to obtain particulate matter.
. The process as claimed in a\ny of Claims 1 to 9 , in which the particulate matter of Moringa 01 ifera is intimately mixed with therapeutic doses of at least one of plant parts selected from a group containing the following: Aegle marmelos (Fruits:ripe and unripe)? Agave vera- cruz (Roots, Leaves, Gum); Allium cepa (Bulb); Allium Sativum Bulb, (Oil);

Aloe darbadnis (Leaves);Bambusa Arundunaceae (Leaves); Boswellia serrata (Gum); Brassica (Oil) ;Cajanu.s cajan (Seeds)jKapparis decidua (Leaves, fruit and stem);Capsicum fruitescens (Fruit); Carum capaticum (Fruits and roots); Celestrus peniculatus (Seed oil, bark, root and fruit); Cicer arietinum (Seeds, leaves); Commiphora mukul (Gum resin); Curcuma amada (Rhizome);Curcuma longa (Rhizome); Cyanopus tetragonoloba (Seed)jEmbelica officinalis (Dried fruit seed, leaves);Embelica ribes Seeds, (fruit and bark);Eugenia cumini (Seeds);Innula recemosa (Root); Juglans regia (kernel,oil); Medicago sativum (Seeds); Momordica charantia (Fruits);Mucuna pruriens (Seeds,fruits,root); Musa Sapientum (Root, stem,flower, fruits,leaves); Nepeta hindostena (Whole plant); Phaseoulus aureus (Seeds); Phaseolus mungu(Seeds); Picrorhiza kurroa (Roat);Piper nigrum (Leaves);Pisum sativum (Seeds); Plantago ovata (Seeds);Pterocarpus marsupium (Gum, leaves); Terminalia arjuna Bark;Sussurea lappa (Root); Thevatia nerifolia Leaves; Trichosanthes dioca (Deseeded fruit powder); Trigonella foenum graecum (Leaves and seeds); and Zingiber officinalis (Rhizome) for conversion into a suitable dosage form.

Documents:

1071-mas-1998 complete specification as granted.pdf

1071-mas-1998 correspondence-others.pdf

1071-mas-1998 correspondence-po.pdf

1071-mas-1998 form-1.pdf

1071-mas-1998 form-4.pdf

1071-mas-98 claims.pdf

1071-mas-98 description (complete).pdf

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Patent Number

235326

Indian Patent Application Number

1071/MAS/1998

PG Journal Number

29/2009

Publication Date

17-Jul-2009

Grant Date

30-Jun-2009

Date of Filing

20-May-1998

Name of Patentee

WHITEFIELD CHEMTECH PVT. LTD

Applicant Address

NEAR RAILWAY STATION, WHITEFIELD, BANGALORE 560 066.

Inventors:

#	Inventor's Name	Inventor's Address
1	ANUBHAI HARIBHAI AMIN	73, KUNJ SOCIETY, ALHAPURI, VADODARA,

PCT International Classification Number

A61K35/78

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA