WO2002049636A1 - Composition antidiabetique a base d'aminoacides - Google Patents

Composition antidiabetique a base d'aminoacides Download PDF

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Publication number
WO2002049636A1
WO2002049636A1 PCT/IN2000/000128 IN0000128W WO0249636A1 WO 2002049636 A1 WO2002049636 A1 WO 2002049636A1 IN 0000128 W IN0000128 W IN 0000128W WO 0249636 A1 WO0249636 A1 WO 0249636A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
glycine
lysine
leucine
glutamic acid
Prior art date
Application number
PCT/IN2000/000128
Other languages
English (en)
Inventor
Rajagopal Thiruvengadam
Malladi Surya Prakasa Sastry
Original Assignee
Rajagopal Thiruvengadam
Malladi Surya Prakasa Sastry
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Rajagopal Thiruvengadam, Malladi Surya Prakasa Sastry filed Critical Rajagopal Thiruvengadam
Priority to PCT/IN2000/000128 priority Critical patent/WO2002049636A1/fr
Priority to AU2001235976A priority patent/AU2001235976A1/en
Publication of WO2002049636A1 publication Critical patent/WO2002049636A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • This invention relates to a novel composition consisting of bio-active and bio-acceptable amino acids for treatment and control of various forms of diabetes.
  • Diabetes Mellitus is an insidious disease, which has no cure at present and is considered to be a major global health problem. About 160 million people all over the world are currently estimated to be suffering from diabetes which according to WHO predictions is likely to cross the 300 million mark by the end of 2025. Incidence of diabetes has increased by 40% among the people in the age group of 40 and by 70% for people in the age group of 30 during 1990-1998. In India alone over 20 million diabetes patients need treatment. Diabetes is estimated to affect a significantly higher percentage of the population in India when compared with other countries. It is noticed that the Indian racial groups settled in other countries also show a higher rate of incidence when compared to other nationalities. These facts clearly indicated that Indians are more prone to diabetes.
  • IDM Insulin Dependant Diabetes Mellitus
  • NIDDM Non Insulin Dependant Diabetes Mellitus
  • Non insulin dependent diabetes can be controlled by proper and regulated diet and exercise. Blood sugar levels may thus be controlled and medication is avoided at least in the early stages of detection and in borderline cases. Howeyer, chronic cases require treatment both insulin and other anti-diabetic drugs. Incidence of this type of diabetes is also found to be on the increase and various anti-diabetic drugs and formulations are available in the market. These drugs act by stimulating insulin secretion, improving absorption of glucose and by increasing insulin sensitivity. In non-insulin dependent diabetes, insulin production may be normal but impaired glucose absorption and consequent increase in blood sugar level may be due to insulin resistance.
  • Major problems facing chronic diabetic patients are diabetic retinopathy, nephropathy, diabetic neuropathy, non- healing diabetic ulcers, neuritis, cataract retinopathy and heart ailments.
  • Proteins are known to stimulate insulin secretion and they do play an important role in the absorption and utilization of dietary carbohydrates. While there have been suggestions on the utility of amino acids for the control of blood sugar in hyperglycemic patients based on animal experiments there has been no systematic evaluation of their utility. For example, it has been reported that cataractogenis could be prevented by preventing glycation of lens proteins mediated by chronic diabetes. This, in turn, has lead to the suggestion lysine or a mixture of amino acids could be useful in the treatment of diabetes. However, it is reported that lowering of blood sugar is not immediate and sustained which lead to the hypothesis that the mechanism may be mostly through the scavenging of glucose by the amino acids administered (Sulochana et. al. Exp.
  • the tripeptide containing glycine, glutamic acid and cysteine residues has been studied with respect to its effect on diabetic animals and patients. It has been surmised that diabetes condition lowers the glutathione content in the liver and reduces the activity of Super oxide dismutase, an enzyme responsible for the elimination of active oxygen radicals, administration of glutathione to diabetic rats led to the recovery of liver glutathione concentration due to increased Super oxide dismutase activity. The impairment of glutathione metabolism weakens the defence mechanism against oxidative stress that the cells experience during the absorption phase of glucose. It has been reported that presence of diabetic complications correlated negatively with the concentration of reduce glutathione. Experimental work with animals has shown the protective effect of glutathione on beta cell toxicity in tiials aimed at reducing the beta cell damage in insulin dependent diabetes.
  • the object of the present invention is to address the basic drawbacks associated with the current management of diabetes, particularly, Non- insulin Dependent Diabetes Mellitus by developing an anti-diabetic preparation which combines many of the desirable features required for an ideal Anti-Diabetic Drug.
  • the essence of the present invention is related to the development of a novel concept for a novel and innovative method of treatment of acute and chronic diabetes and their attendant long-term complications, which affect the various tissues and organs in the human body.
  • the new approach is to utilize the most desirable combination of amino acids, based on their effect on insulin secretion, glucose absorption, insulin resistance, oxidative stress, diabetic cataractogenesis and retinopathy, and vascular complications.
  • the present invention resides in the remarkable finding that a composition of amino acids essentially containing lysine, glycine, leucine, glutamic acid an cysteine which may contain other biologically active and biologically acceptable amino acids has powerful anti diabetic properties.
  • Such compositions are found to exhibit blood sugar reducing properties and also inhibit insulin resistance.
  • Several long-term secondary complications of diabetes such as cataractogenesis, retinopathy, diabetic neuropathy and heart diseases are minimized on treatment with compositions of this invention.
  • a unit dosage of the composition of this invention may have the following composition
  • any known biologically acceptable amino acids may also be added to the composition.
  • composition of amino acids formulated, according to this invention were tested in Streptozotocin induced diabetic rats for its antihyperglycemic activity, in accordance with the defined protocol, with the positive (Phenformin) control and solvent control comparisons.
  • Albino rats of wistar strain of either sex weighing between the narrow range of weight of 150 to 200 gms were selected and were provided with water and standard commercial rat feed ad libitum. Animals were housed at temperature of 18 to 25 degrees C. Diabetes were induced in the rats by the administration of Streptozotocin at a single dose 50mg kg, intraperitonially to overnight fasted animals. Blood glucose levels were estimated by obtaining drop of blood from the tip of the rats toil and placing on a strip of lifescan Inc., USA and the values were measured using the glucometer. Blood glucose is estimated at intervals of 48 and 72 hours after Streptozotocin administration, to the overnight fasted animals which was considered as zero blood glucose value.
  • composition of the present invention contains nutritional principles, safety is guaranteed and toxic effects are bound to be minimum.
  • composition can be administered in a solid dosage form such as plain and coated tablets/hard gelatine capsules/soft gelatine capsules/powder in sachet/liquid dosage form like solution suspension and parental preparations.
  • Different dosage forms are prepared using the conventional excipients and the composition of the excipients may change depending upon the dosage form formulated.
  • Tablets or capsules are formulated by using suitable excipients like microcrystalline cellulose, potato starch, methyl cellulose, hydroxy propyl cellulose, dicalcium phosphate, poly ethylene glycol, hydroxy propyl methyl cellulose, talc, magnesium stearate etc. are used and the process for tabletting normally, not necessarily the same steps.
  • the capsules are formulated in two ways. They are
  • composition with or without the excipients can be used as a powder in a suitable packing like sachet etc..
  • composition can be formulated into a liquid using pharmaceutical vehicles like sorbitol, water, sugar syrup, propylene glycol, glycerine in addition to flavours, buffers, antioxidants and preservatives.
  • pharmaceutical vehicles like sorbitol, water, sugar syrup, propylene glycol, glycerine in addition to flavours, buffers, antioxidants and preservatives.
  • composition and process for extrusion and spheronisation technique is as follows.
  • the above ingredients are sieved through 40# and mixed in a suitable mixer for 30 mnts. And water is added slowly to obtain a soft mass. This is passed through an extruder and then spheronised. The spheronised granules are dried at 45 deg C for about 3 hours or till moisture content is less than
  • These two granules can also be taken as single granules, by taking all the materials together.
  • the blood glucose levels of the test group were 45% lower than that of the control group and 29% lower than that of positive control group.
  • the amino acid mixture could contain the raise in blood glucose level, in test group from the initial level, where as solvent treated control group continued to show significantly increasing blood glucose levels.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Diabetes (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Endocrinology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Emergency Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne une composition sélectionnée contenant de l'hydrochlorure de L-lysine, de la L-leucine, de la L-glycine, de l'hydrochlorure de L-cystéine et de l'acide L-glutamique, laquelle possède des propriétés antidiabétiques efficaces et sûres et qui, en plus de sa capacité à réduire le taux de glucose sanguin chez les diabétiques, peut soulager les complications secondaires du diabète. L'invention concerne, en plus de ladite composition à base des aminoacides mentionnés ci-dessus, des procédés de préparation de différentes formulations présentant les plages de valeurs préférées, et leur utilisation comme agents antidiabétiques.
PCT/IN2000/000128 2000-12-19 2000-12-19 Composition antidiabetique a base d'aminoacides WO2002049636A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/IN2000/000128 WO2002049636A1 (fr) 2000-12-19 2000-12-19 Composition antidiabetique a base d'aminoacides
AU2001235976A AU2001235976A1 (en) 2000-12-19 2000-12-19 An antidiabetic composition of amino acids

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IN2000/000128 WO2002049636A1 (fr) 2000-12-19 2000-12-19 Composition antidiabetique a base d'aminoacides

Publications (1)

Publication Number Publication Date
WO2002049636A1 true WO2002049636A1 (fr) 2002-06-27

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PCT/IN2000/000128 WO2002049636A1 (fr) 2000-12-19 2000-12-19 Composition antidiabetique a base d'aminoacides

Country Status (2)

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AU (1) AU2001235976A1 (fr)
WO (1) WO2002049636A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005110394A1 (fr) * 2004-05-19 2005-11-24 Ajinomoto Co., Inc. Agent thérapeutique pour le diabète
WO2006077202A1 (fr) * 2005-01-18 2006-07-27 Dsm Ip Assets B.V. Nouvelles compositions nutraceutiques
WO2008120797A1 (fr) * 2007-03-30 2008-10-09 Ajinomoto Co., Inc. Activateur d'ampk
US20110237670A1 (en) * 2008-12-12 2011-09-29 Daniel Klamer Improvement of normal cognitive function
US20150011554A1 (en) * 2013-06-13 2015-01-08 Veroscience Llc Compositions and Methods for Treating Metabolic Disorders
WO2015052086A1 (fr) * 2013-10-09 2015-04-16 Nestec S.A. Compositions comprenant de la citrulline et de la leucine et leur utilisation pour traiter le diabète et le syndrome métabolique
EP3615936A4 (fr) * 2017-04-25 2020-12-09 Almeda Labs LLC Formulations d'acides aminés pour la viabilité du pancréas

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4279917A (en) * 1978-09-08 1981-07-21 Ajinomoto Company, Incorporated Amino acid solution for intravenous nutrition
WO1982003773A1 (fr) * 1981-04-27 1982-11-11 Baxter Travenol Lab Solution de dialyse contenant du glucose, des acides amines et de l'insuline
JPS60255722A (ja) * 1984-05-30 1985-12-17 Otsuka Pharmaceut Factory Inc 糖尿病用アミノ酸輸液
EP0917826A1 (fr) * 1997-05-28 1999-05-26 Schwartz Riera, Simon Formules d'aminoacides pour des personnes agees et procede de calcul de celles-ci

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4279917A (en) * 1978-09-08 1981-07-21 Ajinomoto Company, Incorporated Amino acid solution for intravenous nutrition
WO1982003773A1 (fr) * 1981-04-27 1982-11-11 Baxter Travenol Lab Solution de dialyse contenant du glucose, des acides amines et de l'insuline
JPS60255722A (ja) * 1984-05-30 1985-12-17 Otsuka Pharmaceut Factory Inc 糖尿病用アミノ酸輸液
EP0917826A1 (fr) * 1997-05-28 1999-05-26 Schwartz Riera, Simon Formules d'aminoacides pour des personnes agees et procede de calcul de celles-ci

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Week 198605, Derwent World Patents Index; AN 1986-033308, XP002954034 *

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005110394A1 (fr) * 2004-05-19 2005-11-24 Ajinomoto Co., Inc. Agent thérapeutique pour le diabète
JPWO2005110394A1 (ja) * 2004-05-19 2008-03-21 味の素株式会社 糖尿病治療薬
WO2006077202A1 (fr) * 2005-01-18 2006-07-27 Dsm Ip Assets B.V. Nouvelles compositions nutraceutiques
EA012300B1 (ru) * 2005-01-18 2009-08-28 ДСМ АйПи АССЕТС Б.В. Композиция для лечения или предотвращения сахарного диабета и ее применение
WO2008120797A1 (fr) * 2007-03-30 2008-10-09 Ajinomoto Co., Inc. Activateur d'ampk
US20110237670A1 (en) * 2008-12-12 2011-09-29 Daniel Klamer Improvement of normal cognitive function
US20150011554A1 (en) * 2013-06-13 2015-01-08 Veroscience Llc Compositions and Methods for Treating Metabolic Disorders
JP2016521755A (ja) * 2013-06-13 2016-07-25 ヴェロサイエンス，リミテッド・ライアビリティー・カンパニー 代謝障害を治療するための組成物および方法
WO2015052086A1 (fr) * 2013-10-09 2015-04-16 Nestec S.A. Compositions comprenant de la citrulline et de la leucine et leur utilisation pour traiter le diabète et le syndrome métabolique
US9913818B2 (en) 2013-10-09 2018-03-13 Nestec S.A. Compositions comprising citrulline and leucine and their use in the treatment of diabetes and metabolic syndrome
AU2014333977B2 (en) * 2013-10-09 2019-12-19 Société des Produits Nestlé S.A. Compositions comprising citrulline and leucine and their use in the treatment of diabetes and metabolic syndrome
US11419838B2 (en) 2013-10-09 2022-08-23 Societe Des Produits Nestle S.A. Compositions comprising citrulline and leucine and their use in the treatment of diabetes and metabolic syndrome
US11957652B2 (en) 2013-10-09 2024-04-16 Societe Des Produits Nestle S.A. Compositions comprising citrulline and leucine and their use in the treatment of diabetes and metabolic syndrome
EP3615936A4 (fr) * 2017-04-25 2020-12-09 Almeda Labs LLC Formulations d'acides aminés pour la viabilité du pancréas
US11224582B2 (en) 2017-04-25 2022-01-18 Almeda Labs Llc Amino acid formulations for pancreatic viability

Also Published As

Publication number Publication date
AU2001235976A1 (en) 2002-07-01

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