Title of Invention	A SYNERGISTIC REJUVENATING AND REVITALIZING PHARMACEUTICAL COMPOSITION
Abstract	This invention relates to a synergestic rejuvente and revitalising pharmaceutical composition. THe composition consists of the eight essential amino acids useful in metabolic protein synthesis, and vitamins A, C, B complex group, and D and E. pharmaceutically acceptable adijuvants are also added.

Full Text

This invention relates to a synergistic rejuvenating and revitalising pharmaceutical composition. Proteins are complex nitrogenous substances consisting mainly of amino acid residues joined by peptide linkage. A great variety of proteins may be obtained from a small number of amino acids, depending upon the molecular weight of the proteins and their amino acid sequences. Proteins are essential constituents of the living cell and play a very important role in the metabolism of living organism. Structural substances like hair, horns, cartilage, tendons, feathers and the like are made of proteins. Enzymes are biochemical catalysts produced by living cells and are mainly proteinaceous in nature. A balanced diet should evidently contain adequate proteins and amino acids to make good the losses that occur during tissue wastage and other metabolic changes that take place in a living organism constantly. Amino acids are, therefore, the building blocks of proteins. Out of the 23 amino acids, that go into the making of a vast number of proteins, eight are considered essential amino acids. The human body cannot produce the essential amino acids in sufficient quantity and hence they must find a place in the diet to maintain the metabolic activity to promote growth, body building and resistance to diseases. Amino acids are essential for immunity development, tissue maintenance and repair, production of enzymes and hormones, synthesis of proteins in the body, and are promoters of body growth and vitality. Proteins in the diet are hydrolysed by various proteolytic enzymes in the stomach and small intestine to amino acids which are absorbed into the blood stream. These amino acids are used for synthesising body proteins and non protein nitrogenous compounds. They may also be converted into other amino acids, metabolised for releasing energy, glycogen or fats. It is relevant in this connection to state that as the body is unable to synthesise the eight essential amino acids, a balanced diet should contain the proper amount and balance of such amino acids. Vitamins are organic compounds which cannot be synthesised or at least not at an adequate rate, by an organism but are essential in very small quantities for the maintenance of normal health and growth. This necessitates the inclusion of vitamins regularly in ones diet. The foregoing paragraphs highlight the necessity of providing the required quantity of essential amino acids and vitamins as dietary supplements. It has been noticed by us that assimilation of essential amino acids in the body is enhanced if combined with vitamins; Vitamins which form a part of many coenzymes. Coenzymes enhances the catalytic activity of the enzymes in the body fluids. A composition of essential amino acids and vitamins are readily assimilable by the body fluids and the coenzyme in the vitamins triggers the metabolic activity to synthesise body protein, necessary for body building and to release energy required for active life. The object of this invention is to provide a synergestic composition of essential amino acids and vitamins to rejuvenate and revitalise the body by enhanced protein synthesis and easy release of energy. The essential amino acids are (1) Valine, (2) Leucine, (3) Isoleucine, (4) Phenyl alanine, (5) Threonine, (8) Methionine, (7) Tryptophane and (8) Lysine. Addition of 5 Hydroxy anthranilic acid hydro chloride enhances the synergestic action of the amino acid vitamin composition. Conventional adjuvants and excipients are added to the composition of amino acids and vitamins. The synergestic rejuvenating and revitalising pharmaceutical composition according to this invention comprises a blend of the compounds listed hereunder in the range specified thereagainst with known pharmaceutically acceptable adjuvants. L Leucine 13 to 23 mg L Iso leucine 4.5 to 7.5 mg L Lysine hydrochloride 19 to 31 mg L Phenyl alanine 3.5 to 6.5 mg L Threonine 3 to 5 mg L Valine 5 to 8 mg L Tryptophane 3.5 to 6.5 mg DL Methionine 13 to 23 mg 5 Hydroxy anthranilic acid 0.15 to 0.25 Vitamin A acetate 2000 to 3000 lU Vitamin D3 150IUto250IU Vitamin Bl Mononitrate 3.5 to 6.5 mg Vitamin B2 2 to 4 mg Niacinamide 19 to 31 mg Vitamin B6 Hcl 1.2 to 2.6 mg Folic acid 0.2 to 0.9 mg Calcium pantothenate 3.6 to 6.5 mg Vitamin B12 1.0to3.1mg Vitamin C 20 to 60 mg Vitamin E 1 to 9 lU Conventional additives, colourants and excipients are added depending upon the nature of the composition. If a liquid composition is preferred, adjuvants like distilled water and pharmaceutically acceptable solvents are used and the active ingredients specified above are either emulsified or dissolved therein. Tablets or capsules are prepared by suitable substitution of solid adjuvants. The compounding ingredients may be thoroughly mixed and tabletted in the conventional manner. Capsules may also be formed wherein the active ingredients are spheronised and encapsulated in a shell made of pharmaceutically acceptable and bio degradable material. Commonly used excipients or adjuvants and colourants are given below: Col - Tartrazine Col - Erythrocine Col - Indigo-carmine Col - Sunset yellow Titanium dioxide, Lactose, Potato starch, Microcrystalline, Cellulose, Calcium, Carboxy Methyl Cellulose, Methyl cellulose. Hydroxy propyl cellulose. Polyethylene glycol 6000, Synthetic Aluminium Silicate, Stearic acid, Industrial Methylated Spirit, Poly vinyl pyrolidone, Iso Propyl Alcohol, and distilled water. In a preferred embodiment, compatible components of the composition are grouped together, spheronised, dried and then encapsulated. For example, a capsule may contain a plurality of granules, the total composition of which falls within the range specified herein above, but each group of granules may contain a group of compatible components different from the other group. For instance a capsule may contain white, yellow, red, chocolate and orange granules of the composition specified herein below: 1. White granules I: Vitamin B6Hcl 1.725 mg Niacinamide 30 mg Calcium panthothenate 6.5 mg Lactose 8.4 mg Potato starch 3.2 mg Micro Crystalline Cellulose 6.0 mg Calcium Carboxy methyl cellulose 5.5 mg Titanium dioxide 0.1 mg Distilled water 0.01ml The components are mixed in a Planetary mixer for one hour and water is added slowly to obtain a soft mass. This is extruded through an extruder and then spheronised, using murmeriser. The spheronised granules are dried at 45°C for about an hour till the moisture content is reduced to less than 1%. 2. White Granules II: Vitamin Bl (Thiamine mononitrate) 6 mg Micro Crystalline Cellulose 2 mg Potato starch 1 mg Methyl cellulose 0.4 mg Calcium Carboxy methyl cellulose 0.9 mg Titanium dioxide 0.1 mg Water purified 0.01 ml The above ingredients are mixed and granulated as stated in connection with the preparation of White granules No. I. 3. Yellow Granules: DL Methonine 18.3 mg The above ingredients are blended and spheronised as stated under White Granules No. 1 4. Orange Granules: Riboflavin (Vitamin B2) 3.3 mg Folic acid 0.975 mg Vitamin B12 3 meg 5 Hydroxy Anthranilic acid 0.22 mg Lactose 12 mg Potato starch 9 mg Micro Crystalline Cellulose 6 mg Polyethylene Glycol 0.3 mg Calcium Carboxy Methyl Cellulose 0.25 mg Hydroxy Propyl Cellulose 0.8 mg Distilled water 0.01ml The above ingredients are mixed and spheronised as stated herein above. Red Granules: DL-a-Toco pheryl Acetate( Vitamin E Acetate) 16.5 mg L Tryptophan 5 mg Synthetic Aluminium Silicate 3.3 mg Lactose 13.7 mg Micro Crystalline Cellulose 2 mg Polyethylene Glycol 6000 0.1 mg Calcium Carboxy methyl cellulose 2 mg Hydroxy Propyl Cellulose 2 mg Erythrocine (Colour) 0.116 mg Tatrazine (Colour) 0.012 mg Distilled Water 0.01ml Ingredients under item 5 are blended and spheronised in a manner as stated herein above. 6. Chocolate Granules: Ascorbic acid 52.0 mg Stearic acid 1.56 mg Industrial Methylate Spirit 0.008 ml Micro Crystalline Cellulose 2.6 mg Polyethylene Glycol 6000 1.6 mg Calcium Carboxy Methyl Cellulose 2.0 mg Methyl Cellulose 0.6 mg Colour Tartrazine 0.252 mg Colour Erythrocine 0.15 mg Colour Indigo Carmine 0.076 mg Potato Starch 1.8 mg Distilled Water 0.01ml Spheronised granules are made from the above ingredients as stated herein above. 7. A and D Granules: Vitamin A acetate 8 mg Vitamin D3 0.008 mg Lactose 12.6 mg Micro Crystalline Cellulose 3.392 mg Polyvinyl Pyrolidone 2 mg Isopropyl alcohol 0.01 ml Items 1 to 4 stated above are blended and then granulated with a solution of polyvinyl pyrolidone in isopropyl alcohol. Quantities of Vitamins mentioned in the process are inclusive of required overages. Capsules are prepared by mixing the desired quantity of the granules under items 1-7 in the conventional manner. Obvious variatons and equivalents are well within the scope of this invention. The copending applications (1) 186/MAS/95 is directed to "A pharmaceutical composition, for enhancing iron assimilation and haemoglobin synthesis comprising a blend of the compounds listed hereunder in the range specified thereagainst with known adjuvants and/or excipients. Ferrous Fumarate 115 to 185 mg L Histidine hydrochloride 3 to 5 mg L Lysine hydrochloride 19 to 31 mg Glycine 7.5 to 12.5 mg Vitamin Bi mono nitrate 3.75 to 6.25 Riboflavin 2.25 to 3.75 mg Vitamin Be hydrochloride 1.2 to 1.8 mg Vitamin B12 1.9 to 3.1 meg Folic Acid 0.38 to 0.62 mg Ascorbic acid 30 to 50 mg". (2) 187/MAS/95 relates to "A synergistic amino acid composition effective in utilizing excess nitrogen for protein synthesis comprising a blend of the compounds listed herein under in the range specified thereagainst with known pharmaceutically acceptable adjuvants and/or excipients. L-Isoleucine 150 to 250 mg L-Leucine 240 to 400 mg L-Lysine Hydrochloride 220 to 370 mg L-Methionine 240 to 400 mg L-Phenylalanine 240 to 400 mg L-Threonine 110 to 181 mg L-Tryptophan 54 to 90 mg L-Valine 175 to 270 mg L-Histidine Hydrochloride 160 to 270 mg". (3) 188/MAS/95 relates to "A synergistic growth promoting composition comprising a blend of the compounds listed herein below in the range specified thereagainst with pharmaceutically acceptable adjuvants, and/or excipients. L Threonine 0.63 to 1.05 mg L Valine 1 to 1.69 mg L Methonine 1.4 to 2.3 mg L Isoleucine 0.88 to 1.48 mg L Leucine 2.8 to 4.5 mg L Phenyl alanine 0.75 to 1.25 mg L Tryptophan 0.75 to 1.25 mg L Lysine hydrochloride 3.75 to 6.25 mg Vitamin C 75 mg to 125 mg". (4) 189/MAS/95 relates to "An improved purgative composition effective in maintaining electrolyte balance of body fluids comprising a blend of 46 to 74 gms polyethylene glycol, 1.1 to 1.8 gm of sodium chloride, 0.56 to 0.92 gm of potassium chloride, 1.25 to 2.1 gm of sodium bicarbonate and 4.2 to 7 gm of sodium sulphate" EXAMPLE 1 Effect of the present invention (Composition 1) on appetite stimulation in comparison with the other possibiHties: Four formulations of the following composition were prepared in a suitable pharmaceutical form, including the appropriate excipients, by standard methods known to those of ordinary skill in the art. The purpose of this study is to determine the effect of the compositions stated in this invention in increasing the appetite by the method of bile secretion. Method Preferably, the study involves 60 Swiss albino mice of either sex (25 - 30g). Animals were fasted for 18 hours with water allowed ad libitum. They were divided into 5 groups, namely Group 1, served as control that received placebo. Group 2, treated with the composition 1. Animal dose: 178.13 mg/kg of body weight (88.5 mg of amino acid + 89.63 mg of vitamins). Group 3, treated with the composition 2. Animal dose: 88.5 mg/kg of body weight (88.5 mg of amino acid). Group 4, treated with the composition 3. Animal dose: 89.43 mg/kg of body weight (89.43 mg of vitamins) and Group 5, treated with the composition 4. Animal dose: 130.20 mg/kg of body weight (88.5 mg of amino acid + 41.7 mg of vitamins). One hour after drug administration animals were sacrificed. Laparotomy was performed, liver exposed, gall bladder identified and removed along with bile duct from the peritoneal cavity. The isolated gall bladder was weighed before and after removal of the contents. The gall bladder walls were washed with distilled water, dried on filter paper, and the organ was weighed again. The difference in weight of full and empty gall bladder indicates the quantity of bile secreted. These data are shown in table I. EXAMPLE 2 Evaluation of Appetite stimulation by X -ray metliod: Another study was also conducted to confirm the effects of the compositions stated in this present invention in improving the bile secretion. Method 60 female mice (20 -30 g) were fasted for 18 hours with water ad libitum. They were divided into 5 groups and received compositions as described above in example 1. The radio opaque substance lodipamide (0.1339 g/Kg) was administered orally one hour after the drug administration. X-ray pictures were observed at 15"' min, 45*' min, 1 hour and 2 hour. The results are shown in table 2. In groups (1), (3), (4) & (5) the dye reached the gall bladder in 15 min and remained in the bladder for 1 hour. However, in group (2) animals, which were treated with composition 1, the dye did not accumulate in the bladder for long, but reached the intestine within a short interval of 45 rain. This clearly indicates that the composition 1 stated in the present invention improves the bile secretion, gastric emptying and thus stimulates appetite. EXAMPLE 3 Memory enhancement study by radial arm maze method: The compositions stated in the present invention were tested in rats to determine the effect on memory enhancement. Method 60 wistar albino rats of either sex (150 - 180 g) were selected for the 12 days training period followed by 7 day treatment and 3 day lag period allowed, before testing the retention of the learned behavior for 3 consecutive days. Animals were divided in to 5 groups and received compositions as described in example 1. Training period: (1-12 days) The radial arm maze was constructed of wood with 8 arms each of 56 cm long and 10 cm wide extended from an octagonal central platform 35 cm across. The rats were trained with one session per day for twelve days. Each rat was placed in center of the octagon and allowed to enter arms. The time lag to enter the first arm is noted and sequence of entry in to all arms was noted. In each arm, a foot pellet was placed and entry noted when the rat places all 4 paws in to an ann completely. Reentries in to an arm are counted as an error of associative memory. The session was continued until the rat enters all the 8 arms or imtil 10 minutes elapsed whichever comes first. The number of correct responses before the first error and total time taken for each session was also noted. Treatment Period: (13 -19 days) The compositions stated in the present invention were given for 7 days. Lag Period: (20 -22 days) A lag Period of 3 days was provided. The test was performed for 3 consecutive days to measure the retention of learning. The following table summarizes the results of the radial arm maze test. It is clearly showed that the treatment with the invention stated in composition 1 reduces the number of errors and enhances the number of correct entries as compared to that of the learning period. This indicates that the composition 1 disclosed in this invention enhances the retention of the learning behavior. EXAMPLE 4 Passive Avoidance Test: This study employs avoidance tasks to evaluate the compositions stated in the present invention for cognitive enhancement. Method Rats were divided into 5 groups (n=12) and treated similary as described in Example 1. Each rat was placed in the bright compaitment and on transfer into the dai'k compartment, it was given an electric shock (0.5 mA for 5 sees) through floor grid. The duration taken by the rats to transfer from the bright to dark compartment was recorded as transfer latency time (TLT) in seconds. TLT was recorded in control and the composition treated groups on day 1, day 2 and day 9. The electric shock was not administered during the subsequent trials. The data obtained are reported in table 4 below. It can be seen from the table that the group treated with the formulation comprising composition 1 shows the significant increase in TLT compared to other groups. This result ensures the improvement of the retention of the learned passive avoidance memory by the composition 1 disclosed in the present invention. - EXAMPLE 5 Promotion of lean body mass and weight gain: A study is undertaken to evaluate the effectiveness of the compositions of the present invention in weight gaining, more particularly in increasing the lean body mass. Method 60 healthy subjects (70 -72 kg) participated and completed the 12 week program. They were divided into 5 groups (12 in each group). All of them received isocaloric diet. Group (1) served as control Group (2) received one capsule twice a day of the composition 1 stated in example 1. Group (3) received one capsule twice a day of the composition 2 stated in example 1. Group (4) received one capsule twice a day of the composition 3 stated in example 1. Group (5) received one capsule twice a day of the composition 4 stated in example 1. A base line weight and lean body mass were established for each subject and the subjects were again tested periodically throughout the 12 week program. The body weights were checked using digital weighing machine and the lean body mass were measured using Dual Energy X ray Absortiometry (DEXA). The amounts of body weight, lean body mass at base line, week 6 and week 12 are presented in the table 5 as mean + sem. In groups (2), (4) and (5) the lean body weight and the lean body mass were not increased and they approximated to those of group 1. Group (2) subjects showed a remarkable increase in lean body mass and body weight. The results showed that the composition 1 stated in the present invention is effective in improving the lean body mass and body weight. EXAMPLE 6 Evaluation of Anti stress Activity: This study example illustrates the use of the disclosed composition in the improvement of the nutritional status of a subject in a physiologically stressful state. Method 72 male wistar rats (body weight about 300 g) were preliminary fed for one week. During the preliminary feeding period and the experimental period, the rats were restrictively fed with commercial diet and allowed to take water ad libitum. After preliminary feeding period, the rats were divided into seven groups (twelve rats each) namely, Group (1) - Not exposed to stress and given saline. Group (2) - exposed to stress and given saline. Group (3) - exposed to stress and given composition 1 as described in example 1. Group (4) - exposed to stress and given composition 2 as described in example 1. Group (5) - exposed to stress and given composition 3 as described in example 1. Group (6) •- exposed to stress and given composition 4 as described in example 1. The animals of groups (2), (3), (4), (5) and (6) were exposed to stress for 9 days by putting them in a cold room 4 " C for 4 hours per day. On the day 10, rats of group (1) and (2) were given saline. The rats of groups (3), (4), (5) and (6) were given 1 ml of saline containing each composition 1, composition 2, composition 3 and composition 4 respectively, by forcible administration into stomach via an oral sonde. After the administration, the rats of groups (2), (3), (4), (5) and (6) were exposed to cold stress. Two hours after finishing the stress loading, blood pressure of the rats in each group was measured by tail-cuff method using a non warming, non invasive rat sphygmomanometer. The results are shown in table 6. As shown in table 6, both systolic and diastolic pressures were higher in group (2), which were exposed to stress than group (1), which were not exposed to stress. The groups (4), (5) and (6) showed blood pressure similar to that of Group (2). On the contrary both systolic and diastolic blood pressures of group (3) which received composition 1 stated in example 1 were lower than groups (4), (5) and (6) and approximated to those of group (1) rats which were not exposed to stress. From these results, it was confirmed that the administration of composition 1 disclosed in the present invention results in suppression of the increase in blood pressure induced by stress. EXAMPLE 7 Study on acceleration of combustion of body fat: The present invention will be described in the following illustrations to establish the acceleration of combustion of body fat. Method 60 mice (6-8 week old), which had been fasted for 12-16 hours, were divided into 5 groups (n=12). Group 1 served as control, Group 2 received composition 1 as described in example 1, Group 3 received composition 2 as described in example 1, Group 4 received composition 3 as described in example 1 and Group 5 received composition 4 as described in example 1. They were then allowed to stand for 30 minutes and they were subsequently forced to swim in a water flowing pool maintained at 35 C. Incase of the swimming under the application of load, a weight of 0.3 g was attached to the tail of each mouse. The blood was collected from each mouse immediately after the animal was forced to swim for 30 minutes and it was analysed for the metabolites in blood. Blood free fetty acid value: The blood of each test animal was collected by allowing it to stand for 30 minutes, subjecting the blood to centrifixgation at 3000 rpm to thus obtain a supernatant (serum), which was "- used for the determination of the blood free fatty acid value. The variation of blood free fatty acid value during swimming under load was noted. The results were given in table 7. If the amino acid engine is operated effectively, it is expected that the combustion of the body fat is activated or promoted and this in turn leads to an increase in the blood free fatty acid value. As shown in table 7, the blood free fatty acid value of group 2 (animal that received composition 1 stated in example 1) is higher than all of these values observed for other compositions and control. These results clearly indicate or suggest that the foregoing amino acid engine is effectively operated and that the metabolism of the body fat is accelerated. EXAMPLE 8 Immune response: A study was also conducted to compare the immune response of the control group and for the groups receiving the various compositions of the present invention. Immune responses were comparable in all five groups at baseline. However, the adults given the fonnulation comprising composition 1 showed a much higher response in the following parameters tested (table 8) including the number of T-Lymphocytes, CD 4+ helper T cells, Lymphocyte response to mitogen PHA, interleukin 2 production by mitogen stimulated lymphocytes, antibody production after booster injection of tetanus toxoid and natural killer cell activity. Infection rate was determined meticulously and showed a significant reduction in the groups receiving the compositions as shown in Table 8 below. WE CLAIM: A synergestic rejuvenating and revitalising pharmaceutical composition comprising a blend of the compounds listed hereunder in the range specified thereagainst with known pharmaceutically acceptable adjuvants or excipients. L Leucine 13 to 23 mg L Iso leucine 4.5 to 7.5 mg L Lysine hydrochloride 19 to 31 mg L Phenyl alanine 3.5 to 6.5 mg L Threonine 3 to 5 mg L Valine 5 to 8 mg L Tryptophane 3.5 to 6.5 mg DL Methionine 13 to 23 mg 5 Hydroxy anthranilic acid Hcl 0.15 to 0.25 mg Vitamin A acetate 2000 to 3000 lU Vitamin D3 150IUto250IU Vitamin Bl Mononitrate 3.5 to 6.5 mg Vitamin B2 2 to 4 mg Niacinamide 19 to 31 mg Vitamin B6 Hcl 1.2 to 2.6 mg Folic acid 0.2 to 0.9 mg Calcium pantothenate 3.6 to 6.5 mg Vitamin B12 1.0 to 3.1 meg Vitamin C 20 to 50 mg Vitamin E 1 to 9 lU 2. The pharmaceutical composition as claimed in claim 1 wherein the blend is in the form of an emulsion or suspension. 3. The pharmaceutical composition as claimed in claim 1 wherein the blend is in the form of tablets. 4. The pharmaceutical composition as claimed in claim 1 wherein the blend is in the form of granules/pellets encapsulated in a pharmaceutically acceptable casing. 5. The pharmaceutically acceptable composition as claimed in claims 1 to 4, wherein blends of spheronised compatible compounds are encapsulated. 6. The pharmaceutically acceptable composition as claimed in claims 1 to 5 which additionally contains colourants. 7. The pharmaceutically acceptable composition as claimed in claims 1 to 6, wherein different granules are differently coloured. 8. A synergestic rejuvenating and revitalising pharmaceutical composition, substantially as herein described and exemplified.

Documents:

185-mas-1995 abstract duplicate.pdf

185-mas-1995 abstract.pdf

185-mas-1995 claims duplicate.pdf

185-mas-1995 claims.pdf

185-mas-1995 correspondence others.pdf

185-mas-1995 correspondence po.pdf

185-mas-1995 description (complete) duplicate.pdf

185-mas-1995 description (complete).pdf

185-mas-1995 form-1.pdf

185-mas-1995 form-18.pdf

185-mas-1995 form-26.pdf