Title of Invention

A PHARMACEUTICAL COMPOSITION FOR ENHANCING IRON ASSIMILATION AND HAEMOGLOBIN SYNTHESIS

Abstract

ABSTRACT 186/M AS/95 "A pharmaceutical composition for enhancing iron assimilation and haemoglobin synthesis" This invention relates to a pharmaceutical composition for enhancing iron assimilation and haemoglobin synthesis. The composition contains L Histidine hydrochloride, L Lysine Hydrochloride, Glycine, Vitamin B Compounds, ascorbic acid and an assimilable iron compound. The composition also has pharmaceutically acceptable adjuvants.

Full Text

This invention relates to a pharmaceutical composition for enhancing iron assimilation and haemoglobin synthesis. Proteins are complex nitrogen containing substances consisting mainly of amino acid residues joined by peptide linkage. A great variety of peptides may be obtained from a small number of amino acids depending upon the molecular weight of proteins and the amino acid sequencing. But amino acids are not the only compounds that go into the making of a protein, there are glyco-proteins, nucleo-proteins, lipo proteins, chromo proteins and the like where conjugate groups like a carbohydrate, a fat, nucleic acid and the like conjugate with amino acid residues. Haemoglobin, the oxygen carrying molecule in red blood cells is a conjugated protein of four heme groups which are organo metallic compounds containing iron. Diminution of the amount of total circulating haemoglobin in the blood stream causes anaemia. Absence of iron in food intake or improper assimilation of iron intake by the system cause anaemia. Growing children, women and convalescents require more haemoglobin and their diets are often supplemented with iron containing compounds. It has been established that amino acids are the building blocks of proteins and out of the 23 amino acid that are generally found in proteins only eight are not produced in the system. These eight essential amino acids should fmd a place in sufficient quantities in the daily intake of food for proper growth and vitality. Out of the eight essential amino acids, three are found to play a role in the synthesis of haeinoglobin in addition to their role in protein synthesis. They are glycine, histidine and lysine. It is observed that when combined with iron, these amino acids undergo metabolic changes to produce haemoglobin. Vitamins are heterogeneous organic compounds essential in small quantities for the maintenance of norma! heahh and growth. Vitamins cannot be synthesised during metabolic action and are to be included in the food intake regularly. Out of the many vitamins required by the body, the B group of Vitamins are water soluble and are eliminated from the system easily. Deficiency of B group vitamins is known to cause weight loss. Pellagra, Neuro muscular disorders, Beri Beri anaemia and the like. Yet another water soluble vitamin is Vitamin C which is essential for intracellular collagen in Vitamin C deficiency leads to Scurvy which causes anaemia. It has been established that assimilation of iron by the metabolism is enhanced if combined with Vitamin C. The object of this invention is to provide a synergestic composition of amino acids, vitamins and iron compounds which enhances the assimilation of iron thereby increasing the production of haeinoglobin. The role of iron and Vitamin B group in controlling anaemia has been well recognized. It has now been established that three essential amino acids, glycine, histidine and lysine which are essential in the formation of haemoglobin improves iron absorption considerably. A combination of Vitamin B Complex and C with the said three essential amino acids and iron compounds is found to have increased iron assimilation and consequently haemoglobin synthesis. This invention provides a pharmaceutical composition for enhancing iron assimilation and haemoglobin synthesis which comprises blending compounds listed hereunder in the range specified there against with known adjuvants and/or excipicnts. Conventional additives colourants and excipients may be added depending upon the nature of the composition. For instance, if a liquid composition is desired pharmaceutically acceptable liquid carriers are added and the compounding ingredients are either dissolved therein or emulsified. Flavouring and colouring agents may also be added to the composition. Tablets or capsules may be prepared by tablening the active ingredients specified above with known pharmaceuticaily acceptable compounds while making capsules, the compounds are spheronised either together or in groups which is then encapsulated within shells made of pharmaceuticaily acceptable and biologically degradabie materials. In a preferred embodiment compatible components of the composition are grouped together, spheronised, dried and encapsulated together. For instance, a composition may contains a plurality- of granules, the total composition of which falls within the range specified hereinabove while each group of granules may contain a group of compatible components different from the other group. For example, a single capsule may contain pink, orange, yellow, blue and brown granules of the The ingredients are well mixed and blended with water to form a uniform mass which is extruded and spheronised to form granules. The granules are then dried at 45°C in a fluidised bed to a moisture content of 1.1 or below. The granules are stored in a cold place till required. Methyl cellulose 3 mg Colour Tartrazine 0.3 mg Distilled water 0,01 ml . The above components are granulated as stated under Item 1 and stored in a cool place. 4. Blue Granules: Absorbic acid 56 mg Stearic acid 1.6 mg Industrial Methylated Spirit 0.008 ml Lactose 16 mg Maize starch 5 mg Micro Crystalline Cellulose 4 mg Sodium Carboxy Methyl Cellulose 4.0 mg Polyethylene Glycol 6000 4.8 mg Methyl Cellulose 1.4 mg Colour Indigo Carmine 0,4 mg Distilled water 0.01 ml The above ingredients are blended and granulated as given under item no. I and stored in a cool place till required. 5. Brown Granules: Ferrous Fumerate 161 mg Maize Starch 27 mg Micro Crystalline Cellulose 4,8 mg Sodium Carboxy Methyl Cellose I mg Sucrose 33 mg Water Purified 0,01 ml Methyl Cellulose 3 mg Acetone 0.039 ml Methylene Chloride 0.039 ml Castor oil 0.38 mg The above ingredients are blended and granulated as given under Item No. 1 and stored in a cool place till required. All the above five granulates are blended as required and encapsulated in the known manner keeping the ratio of individual components within the range specified herein above. The quantities of vitamins mentioned in the process are inclusive of required overages. The copending applications (1) 185/MAS/95 is directed to "A synergestic rejuvenating and revitalising pharmaceutical composition comprising a blend of the compounds listed hereunder in the range specified thereagalnst 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 3! mg L Phenyl alanine 3.5 to 6.5 mg L Threonine 3 to 5 mg L Valine 5 lo 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 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 1,-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". 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 I'hreonine 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" It is to be understood that obvious modifications and alterations known to persons skilled in the art are within the scope of this invention and the appended claims. EXAMPLE 1 Clinical Trials The following compositions according to the present invention, along with other pharmaceutically acceptable excipients, may be formulated into a suitable pharmaceutical formulation, more particulariy capsule but not limiting to the same. A randomized, single blinded, familiarization trial was performed to compare the efficiency of the haematinics stated in the above said composition 1 and composition 2 with composition 3. which is one of the haematinics currently marketed for the treatment of iron deficiency anaemia. The study involves the comparison of the efficacy of the above said compositions in pregnancy associated anaemia. 30 Pregnant women between 20 + 2 weeks of the gestation were selected and divided info 3 groups, namely Group 1, received formulation comprising composition 1. Group 2, received formulation comprising composition 2. Group 3, received formulation comprising composition 3. A baseline and periodic observations were recorded for the following parameters during the two month study period. 1. Haemoglobin level 2, RBC Count 3. Packed cell Volume 4, Peripheral Smear. The resuhs are shown in tabic 1 From the above table, the group (1) who received composition 1, the mean haemoglobin level that was 10,5 gm/dl at the baseline, had been increased to 12,1 gm/dl after 2 months of therapy. In the groups (2) and (3) the mean haemoglobin level that was at 10.4 gm/dl at baseline were increased to 10,9 gm/dl and 10.8 gm/di respectively after treatment. The changes observed with the group (1), treated with the composition 1 was significant (p=0,02) when compared with other groups. In Group (2) the RBC count at baseline, 3.53 miliions/cu mm increased to 3.69 miliions/cu ram and the packed cell volume was increased from 34,2 % to 34.7 % after therapy. In the case of group (3) the RBC count increased from 3.46 millions/cu mm to 3,70 millions/cu mm and the packed ceil volurne increased from 34.1 % lo 34.9 % after two month treatment. Whereas in Group (1), the RBC count 3.47 millions/cu mm at baseline was increased to 4.10 millions/cu mm and the packed ceil volume that was 33.5 % at baseline is elevated to 37.5 % These changes observed with the group (I) are significant at (p= 0.03) for RBC count and {p=O.0019) for Packed cell volume when compared with other two groups. The peripheral smear showed microcytic hypochromic cells in all groups at baseline. However, after therapy the patients who received formulation comprising the composition 1 got back their normocytic normochromic cells. In the other groups, the peripheral smear microcytic hypochromic cells were persisting even after the two months therapy. This results shows that the present invention stated in composition 1 is both clinically as well statistically significant in increasing the haemoglobin level, RBC count and packed ce)l volume. WE CLAIM: 1. 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 B1 mono nitrate 3.75 to 6.25 Riboflavin 2.25 to 3.75 mg Vitamin B6 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. The composition as claimed in claim 1. wherein the blend is in the form of an emulsion suspension or solution in known pharmaceutically acceptable adjuvants or carriers. 3. The composition as claimed in claim 1 wherein the blend is in the form of tablets. 4. The composition as claimed in claim 1 wherein the blend is in the form of granules encapsulated in pharmaceutically acceptable casing. 5. The composition as claimed in claims 1 to 4 wherein the blends of spheronised compatible compounds are encapsulated. 6. The composition as claimed in claims 1 to 5 having colourants. 7. The composition as claimed in claims 1 to 6 wherein different granules are differently coloured. 8. A pharmaceutical composition for enhancing iron assimilation and haemoglobin synthesis substantially as herein described.

Documents:

186-mas-1995 abstract-duplicate.pdf

186-mas-1995 abstract.pdf

186-mas-1995 claims-duplicate.pdf

186-mas-1995 claims.pdf

186-mas-1995 correspondence-others.pdf

186-mas-1995 correspondence-po.pdf

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

186-mas-1995 description (complete).pdf

186-mas-1995 form-1.pdf

186-mas-1995 form-18.pdf

186-mas-1995 form-26.pdf

186-mas-1995 others.pdf