WO1998041113A2 - Medical food for diabetics - Google Patents

Medical food for diabetics Download PDF

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Publication number
WO1998041113A2
WO1998041113A2 PCT/IT1998/000049 IT9800049W WO9841113A2 WO 1998041113 A2 WO1998041113 A2 WO 1998041113A2 IT 9800049 W IT9800049 W IT 9800049W WO 9841113 A2 WO9841113 A2 WO 9841113A2
Authority
WO
WIPO (PCT)
Prior art keywords
composition
carnitine
vitamin
pharmacologically acceptable
acetyl
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/IT1998/000049
Other languages
English (en)
French (fr)
Other versions
WO1998041113A3 (en
Inventor
Claudio Cavazza
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sigma Tau Industrie Farmaceutiche Riunite SpA
Original Assignee
Sigma Tau Industrie Farmaceutiche Riunite SpA
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 Sigma Tau Industrie Farmaceutiche Riunite SpA filed Critical Sigma Tau Industrie Farmaceutiche Riunite SpA
Priority to DK98908280T priority Critical patent/DK0971600T3/da
Priority to SI9830491T priority patent/SI0971600T1/xx
Priority to IL13154898A priority patent/IL131548A/en
Priority to KR10-1999-7008602A priority patent/KR100496957B1/ko
Priority to AT98908280T priority patent/ATE241916T1/de
Priority to CA002284909A priority patent/CA2284909C/en
Priority to SK1281-99A priority patent/SK283853B6/sk
Priority to PL98335649A priority patent/PL190526B1/pl
Priority to BR9808348-1A priority patent/BR9808348A/pt
Priority to EP98908280A priority patent/EP0971600B1/en
Priority to HK00102413.5A priority patent/HK1025483B/en
Priority to HU0002196A priority patent/HUP0002196A3/hu
Priority to DE69815323T priority patent/DE69815323T2/de
Priority to NZ337129A priority patent/NZ337129A/xx
Priority to JP54029398A priority patent/JP4125791B2/ja
Priority to AU66353/98A priority patent/AU726066B2/en
Publication of WO1998041113A2 publication Critical patent/WO1998041113A2/en
Publication of WO1998041113A3 publication Critical patent/WO1998041113A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • 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
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/328—Foods, ingredients or supplements having a functional effect on health having effect on glycaemic control and diabetes

Definitions

  • the present invention relates to a therapeutic/nutritional composition (medical food) for diabetics.
  • Diabetes mellitus is a complex syndrome of differing genetic, environmental and pathogenetic origin.
  • This syndrome in any event is characterised by hyperglycaemia due to impaired insulin secretion and/or efficiency, associated with a risk of diabetic ketoacidosis or non- ketotic hyper-glycaemic-hyperosmolar coma.
  • hyperglycaemia due to impaired insulin secretion and/or efficiency, associated with a risk of diabetic ketoacidosis or non- ketotic hyper-glycaemic-hyperosmolar coma.
  • nephropathy, retinopathy, atherosclerotic coronary disease, peripheral arteriopathies and neuropathies of the autonomic nervous system are nephropathy, retinopathy, atherosclerotic coronary disease, peripheral arteriopathies and neuropathies of the autonomic nervous system.
  • insulin-dependent diabetes mellitus type 1 DM
  • non-insulin-dependent diabetes type 2 DM
  • Type 1 DM which commonly develops in infancy or during adolescence, is characterised clinically by hyperglycaemia and a predisposition to diabetic ketoacidosis. Chronic insulin treatment is necessary to control the disease.
  • Type 2 DM is characterised clinically by hyperglycaemia not associated with a predisposition to diabetic ketoacidosis.
  • the hyperglycaemia stems both from an abnormal insulin secretory response to glucose and from "insulin- resistance", i.e. from a reduced activity of insulin itself.
  • Diabetics should therefore increase their intake of nutrients capable of enhancing the body's ability to metabolise glucose and insulin. Lastly, they should increase their intake of nutrients which reduce the risk of diabetic complications.
  • a number of micronutrients perform both the second and third functions.
  • ./. and other micronutrients are capable of contributing towards protecting diabetic patients from complications such as heart disease, peripheral neuropathy, retinopathy, kidney failure, frequent infections and slow wound healing.
  • complications such as heart disease, peripheral neuropathy, retinopathy, kidney failure, frequent infections and slow wound healing.
  • particular attention has been focused upon the development of medical foods for diabetics which contribute, along with suitable pharmacological treatment, towards lowering plasma glucose levels.
  • EP 0 659 349 Al (Bristol- Myers Squibb Co.) describes a medical food of this type in which the characterising ingredient is myo-inositol, the hypoglycaemic activity of which was, moreover, already well known.
  • Essential fatty acids such as linoleic acid and alpha- linolenic acid (parent acids of the omega-6 and omega-3 essential fatty acid series, respectively) are nutritional substances which, like vitamins, have to be supplied via the diet, in that they are not biosynthesised by the body.
  • An object of the present invention is to provide a medical food for diabetics which enables them to compensate for the reduced metabolism of essential fatty acids typical of such subjects.
  • the object of the present invention is to provide a medical food of this type which makes it possible to by-pass the enzyme blockade caused by the reduced activity of omega-6-desaturase which occurs in diabetics and gives rise to inadequate conversion of linoleic acid into ⁇ -linolenic acid and thus to a reduced production of prostaglandin and leukotriene precursors.
  • the therapeutic/nutritional composition for diabetics of the present invention comprises a mixture of: (a) ⁇ -linolenic acid or a pharmacologically acceptable salt thereof; and (b) at least one alkanoyl-L-carnitine wherein the alkanoyl group is a straight or branched alkanoyl having 2-6 carbon atoms, or a pharmacologically acceptable salt thereof; wherein the amounts of (a) and (b) are effective to exert a synergistic effect in compensating for the defects of the essential fatty acid metabolism and preventing diabetic complications, particularly diabetic neuropathy, and bringing about regression thereof.
  • the alkanoyl-L-carnitine is selected from the group comprising acetyl-, propionyl-, butyryl-, valeryl-, and isovaleryl-L-carnitine or a pharmacologically acceptable salt
  • acetyl-L-carnitine and propionyl-L-carnitine are particularly preferred.
  • pharmacologically acceptable salts of an alkanoyl-L-carnitine are any of its salts with an acid that does not give rise to unwanted side effects.
  • Such acids are well known t o pharmacol ogists and to experts in pharmacy and pharmaceutical technology.
  • composition of the present invention may further comprise vitamins, metals, coenzymes, organic or inorganic antioxidants or precursors thereof.
  • the coenzyme is coenzyme Q 10
  • the organic antioxidant is selected from the group comprising lipoic acid, resveratrol and glutathione and a preferred precursor is N-acetyl-
  • composition according to the invention comprises in admixture the following components: ⁇ -linolenic acid or a pharmacologically acceptable salt thereof; acetyl-L-carnitine or a pharmacologically acceptable salt thereof; Taurine; Pantethine: Vitamin A; Vitamin E; Vitamin B, ; Vitamin B 6 ; Vitamin B 12 ; Magnesium; Calcium; Zinc; Selenium; Chromium; and Vanadium.
  • a second preferred embodiment of composition further comprises coenzyme Q 10, lipoic acid and myo-inositol.
  • a third preferred embodiment of composition comprises all the components of the first or second composition, a mixture of acetyl- and propionyl-L-carnitine (molar ratio from 10: 1 to 1 : 10) substituting for acetyl-L-carnitine alone.
  • composition of the invention can advantageously comprise also a fat source, a protein source and a carbohydrate source sufficient to meet the caloric daily need of a diabetic individual.
  • this nutritionally complete composition comprises form 10 to 15% of proteins, from 35 to 45% of lipids and from 40 to 50% of carbohydrates, the percentages being calculated on the overall caloric intake of the composition.
  • any rate it was found advantageous that anyone of the compositions of the present invention, suitable both for a monodose administration regimen and a multidose administration regimen, be apt to supply 350-500 mg/day of ⁇ -linolenic acid and 1.5-2.5 mg/day of acetyl-L-carnitine.
  • ⁇ -linolenic acid and the alkanoyl-L-carnitine act synergistically in enhancing the compensation of defects in essential fatty acids metabolism, or the prevention or reversal of diabetic complications, particularly diabetic neuropathy.
  • composition components are valuable for the following reasons:
  • Taurine one of the most abundant amino acids in the body, is found in the central nervous system, skeletal muscles an d is very concentrated in the brain and heart. Taurine deficiency is associated with retinal degeneration.
  • Diabetic patients have below-normal levels of taurine in blood and platelets. Taurine administration to insulin-dependent patients was demonstrated to reduce platelet aggregation and prevent retinopathy by preventing blood clots in retinal vessels.
  • Pantethine is a constituent of coenzyne A, which facilitates energy production through enhancement of the metabolic pathways of fatty acid ⁇ -oxidation and the formation of acetyl-CoA.
  • Vitamin A whose Recommended Dietary Allowance (RDA) is 1000 ⁇ g/day for adult males and 800 ⁇ g/day for adult females, has a diphasic concentration-dependent effect on insulin release. At low concentrations, vitamin A stimulates insulin release while at high concentrations it has an inhibitory effect which may be mediated in part by impairement of intracellular glucose oxidation.
  • RDA Recommended Dietary Allowance
  • Vitamin A administration to type II diabetic patients reduces insulin resistance and hastens the healing process by stimulating collagen synthesis.
  • Vitamin E is the most active antioxidant agent present in biological membranes where it protects cellular structures against damage from oxygen free radicals and reactive products of lipid peroxidation, thus contributing to membrane stability. Platelet activity and eicosanoid production can be normalized by vitamin E supplementation in diabetic patients.
  • Vitamin B l whose RDA is 0.5 mg/ l OOKcalories (a minimal intake of 1 mg/day is recommended) plays a key role in energy metabolism.
  • the daily requirement of vitamin B l is dependent on the intake of carbohydrates.
  • Vitamin B6 RDA is about 2 mg/day in normal adults.
  • Vitamin B6 occurs in 3 forms: pyridoxine hydrochloride, pyridoxal and pyridoxamine and is a component of approximately 120 enzymes.
  • pyridoxal phosphate In the form of pyridoxal phosphate it is a cofactor in the metabolism of amino acids and neurotransmitters and in the breakdown of glycogen; it can bind to steroid hormone receptors and can have a role in the regulation of their action. Pyridoxine is involved in hemoglobulin formation.
  • Plasma vitamin B6 is often low in diabetic patients; those with poor control of blood glucose have more pronounced deficiency.
  • Pharmacological doses of viamin B6 can reverse the abnormalities of tryptophan metabolism and may improve carbohydrate tolerance.
  • Vitamin B 12 (RDA 2 ⁇ g/day, usual intake 4-8 ⁇ g/day) plays a pivotal role in amino acid metabolism.
  • the B 12 coenzyme catalyzes amino and fatty acid breakdown.
  • Vitamin B 12 deficiency is associated particularly with insulin-dependent diabetes mellitus. Pernicious anemia and diabetes mellitus can occur in the same individual as part of a polyglandular autoimmune syndrome.
  • Magnesium (RDA 350 mg/day for adult males and 280 mg/day for females) plays an essential role in many enzymatic reactions such as the transfer of phosphate groups, the acylation of CoA and the hydrolysis of phosphate and pyrophosphate; it is important for the activation of amino acids, the aggregation of ribosomes and the synthesis and degradation of DNA.
  • Magnesium is involved in glucose homeostasis at multiple levels: it is a cofactor in the glucose transport system of plasma membranes; has an important role in activity of various enzymes involved in glucose oxidation, may play a role in release of insulin, and can modulate the mechanisms of energy transfer from high-energy phosphate bonds.
  • Diabetes mellitus is associated with increased urinary loss o f magnesium especially when hyperglycemia is poorly controlled. Plasma magnesium concentration in diabetic patients is reduced. Of particular concern is the large urinary magnesium loss during diabetic ketoacidosis that causes hypomagnesemia and can induce lifethreatening effects on myocardium, skeletal muscles and is implicated in insulin resistance.
  • Magnesium deficiency has been linked to two common complications of diabetes, namely retinopathy and ischemic heart disease.
  • RDA Reactive Calcium
  • Diabetic patients are at increased risk for osteoporosis, presumably due to increased urinary calcium loss.
  • Zinc plays structural, enzymatic and regulatory roles. It participates to the activity of over 60 enzymes such as c arb o xyp epti das e , c arb oni c anhy dras e and al c o ho l dehydrogenase. It has a role in neuronal activity and memory and is necessary for the maintenance of normal plasma levels of Vitamin A.
  • Diabetes mellitus may lead to zinc deficiency.
  • Low blood zinc and hyperzincuria have been reported in initial stages of both Type I and Type II diabetes mellitus.
  • Zinc is well established as playing a role in wound healing and maintenance of skin integrity because of its promoting activity in protein synthesis, cellular replication and collagen formation.
  • Intake (ESADDI) for adults of both sexes is from 50 to 200 mg/day.
  • Chromium is an essential nutrient required for normal carbohydrate and lipid metabolism. It is a component of the biological active glucose-tolerance factor whose deficiency is implicated in the pathogenesis of some forms of glucose intolerance and diabetes mellitus.
  • Urinary chromium excretion tends to increase in diabetics.
  • Vanadium's ESADDI is about 100 ⁇ g/day; bioavailability is very low, generally less than 1 %.
  • Vanadium has an insulin-like behaviour in insulin-dependent diabetics. It either mimics the effects of insulin or increases its efficiency, reducing both glucose and insulin levels.
  • Th e administration of vanadium to type II diabetic patients improves glucose tolerance, lowers blood glucose levels and decreases blood cholesterol levels.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nutrition Science (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Mycology (AREA)
  • Diabetes (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Peptides Or Proteins (AREA)
PCT/IT1998/000049 1997-03-20 1998-03-10 Medical food for diabetics Ceased WO1998041113A2 (en)

Priority Applications (16)

Application Number Priority Date Filing Date Title
DK98908280T DK0971600T3 (da) 1997-03-20 1998-03-10 Medicinsk levnedsmiddel til diabetikere
SI9830491T SI0971600T1 (en) 1997-03-20 1998-03-10 Medical food for diabetics
IL13154898A IL131548A (en) 1997-03-20 1998-03-10 Medical food for diabetics
KR10-1999-7008602A KR100496957B1 (ko) 1997-03-20 1998-03-10 당뇨병 환자용 의료식
AT98908280T ATE241916T1 (de) 1997-03-20 1998-03-10 Therapeutische nahrung für diabätiker
CA002284909A CA2284909C (en) 1997-03-20 1998-03-10 Medical food for diabetics
SK1281-99A SK283853B6 (sk) 1997-03-20 1998-03-10 Terapeutická/výživová kompozícia pre diabetikov
PL98335649A PL190526B1 (pl) 1997-03-20 1998-03-10 Leczniczo-odżywczy preparat dla osób chorych na cukrzycę
BR9808348-1A BR9808348A (pt) 1997-03-20 1998-03-10 Alimento medicinal para diabéticos
EP98908280A EP0971600B1 (en) 1997-03-20 1998-03-10 Medical food for diabetics
HK00102413.5A HK1025483B (en) 1997-03-20 1998-03-10 Medical food for diabetics
HU0002196A HUP0002196A3 (en) 1997-03-20 1998-03-10 Medical food for diabetics
DE69815323T DE69815323T2 (de) 1997-03-20 1998-03-10 Therapeutische nahrung für diabätiker
NZ337129A NZ337129A (en) 1997-03-20 1998-03-10 Medical food for diabetics comprising a mixture of linolenic acid and alkanoyl-L-carnitine
JP54029398A JP4125791B2 (ja) 1997-03-20 1998-03-10 糖尿病患者用医療栄養物
AU66353/98A AU726066B2 (en) 1997-03-20 1998-03-10 Medical food for diabetics

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITRM97A000155 1997-03-20
IT97RM000155A IT1291113B1 (it) 1997-03-20 1997-03-20 Composizione nutritiva terapeutica per soggetti affetti da diabete mellito

Publications (2)

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WO1998041113A2 true WO1998041113A2 (en) 1998-09-24
WO1998041113A3 WO1998041113A3 (en) 1998-12-17

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PCT/IT1998/000049 Ceased WO1998041113A2 (en) 1997-03-20 1998-03-10 Medical food for diabetics

Country Status (21)

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US (1) US6063820A (https=)
EP (1) EP0971600B1 (https=)
JP (1) JP4125791B2 (https=)
KR (1) KR100496957B1 (https=)
CN (1) CN1097436C (https=)
AT (1) ATE241916T1 (https=)
AU (1) AU726066B2 (https=)
BR (1) BR9808348A (https=)
CA (1) CA2284909C (https=)
CZ (1) CZ293196B6 (https=)
DE (1) DE69815323T2 (https=)
DK (1) DK0971600T3 (https=)
ES (1) ES2201451T3 (https=)
HU (1) HUP0002196A3 (https=)
IL (1) IL131548A (https=)
IT (1) IT1291113B1 (https=)
NZ (1) NZ337129A (https=)
PL (1) PL190526B1 (https=)
PT (1) PT971600E (https=)
SK (1) SK283853B6 (https=)
WO (1) WO1998041113A2 (https=)

Cited By (32)

* Cited by examiner, † Cited by third party
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WO2000011968A1 (en) * 1998-09-01 2000-03-09 Sigma-Tau Healthscience S.P.A. ANTIOXIDANT COMPOSITION COMPRISING ACETYL L-CARNITINE AND α-LIPOIC ACID
WO2000021526A1 (en) * 1998-10-09 2000-04-20 Sigma-Tau Healthscience S.P.A. Combination of carnitines and resveratrol for prevention or treatment of cerebral and ageing disorders
WO2000007581A3 (en) * 1998-08-03 2000-05-11 Sigma Tau Healthscience Spa Antioxidant, antiproliferous composition, comprising a carnitine and a carotenoid
WO2000062773A1 (en) * 1999-04-16 2000-10-26 Sigma-Tau Healthscience S.P.A. Composition comprising a carnitine and glutathione, useful to increase the absorption of glutathione and synergize its effects
US6203819B1 (en) 1997-03-07 2001-03-20 Akesis Pharmaceuticals, Inc. Dietary supplement and method of treatment for diabetic control
WO2001007039A3 (en) * 1999-07-28 2001-03-29 Sigma Tau Healthscience Spa L-acetylcarnitine and l-propionylcarnitine containing composition for the prevention and treatment of kidney dysfunctions and diseases
WO2000064426A3 (en) * 1999-04-22 2001-05-25 Sigma Tau Healthscience Spa Carnitine and inositol phosphate-containing composition useful as dietary supplement or drug
WO2001064203A3 (en) * 2000-03-02 2002-03-28 Sigma Tau Healthscience Spa Composition for the prevention and/or treatment of vascular diseases, comprising propionyl l-carnitine and coenzyme q¿10?
US6376549B1 (en) 1998-09-17 2002-04-23 Akesis Pharmaceuticals, Inc. Metforimin-containing compositions for the treatment of diabetes
JP2002293711A (ja) * 2001-03-23 2002-10-09 General Topics Srl リポ酸及びポリエノール脂肪酸に基づく有効成分
JP2002348244A (ja) * 2001-05-23 2002-12-04 Fancl Corp 抗糖尿病組成物
WO2002043507A3 (en) * 2000-11-30 2003-03-06 Health Res Inst Nutrient supplements and methods for treating autism and for preventing the onset of autism
EP1325747A3 (en) * 2001-12-20 2003-07-30 Health Pharma S.r.l Dietary supplement for neuropaths
WO2003077895A1 (en) * 2002-03-20 2003-09-25 Kaneka Corporation Compositions for diabetes
WO2002036202A3 (en) * 2000-11-02 2004-01-08 Nutrition 21 Inc Methods and compositions for the improvement of insulin sensitivity, reduction of hyperglycemia, and reduction of hypercholesterolemia with chromium complexes and alpha lipoic acid
US6852760B1 (en) 1998-09-17 2005-02-08 Akesis Pharmaceuticals, Inc. Compositions and methods for treatment for glucose metabolism disorders
EP1537896A1 (de) * 2003-12-03 2005-06-08 Franz-Peter Dr. Liebel Stoffgemische basierend auf schwefelhaltigen Aminosäuren, Antioxidantien, Phospholipiden und Vitaminen zur Herstellung eines Arzneimittels für die Behandlung des L-Diabetes und/oder assoziierter Erkrankungen
JP2005518381A (ja) * 2001-12-19 2005-06-23 ザ キグリー コーポレーション 抹消神経・血管疾患の治療方法
WO2007016949A1 (en) * 2005-07-29 2007-02-15 Matuschka-Greiffenclau Markus Composition for reducing the risc of alcohol induced neuropathy
WO2007017139A1 (en) * 2005-07-29 2007-02-15 Tima Foundation Composition for moderating alcohol metabolism and for reducing the risk of alcohol induced diseases
WO2005065667A3 (en) * 2003-12-29 2008-01-17 Harvard College Compositions for treating or preventing obesity and insulin resistance disorders
WO2007113540A3 (en) * 2006-04-05 2008-03-13 Univ Nottingham Regulating fat and carbohydrate oxidation in muscle tissue comprising controlling carnitine content in muscle
US7410659B2 (en) 2002-11-06 2008-08-12 The Quigley Corporation Methods for the treatment of peripheral neural and vascular ailments
WO2008141897A1 (en) * 2007-05-24 2008-11-27 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Composition useful for the prevention of adverse effect due to the use of ppar-gamma agonists
JP2009067809A (ja) * 1999-09-03 2009-04-02 Sigma-Tau Industrie Farmaceutiche Riunite Spa 超微細ｌ−カルニチン、その調製方法、それを含む組成物、及びその使用方法
US7914823B2 (en) 2000-12-21 2011-03-29 Prophase Labs, Inc. Method and composition for the topical treatment of diabetic neuropathy
US8535708B2 (en) 2004-12-29 2013-09-17 Hill's Pet Nutrition, Inc. Methods for inhibiting a decline in learning and/or memory in animals
US8592478B2 (en) 2000-10-31 2013-11-26 Hill's Pet Nutrition, Inc. Antioxidant-containing food composition
US8669282B2 (en) 2000-10-31 2014-03-11 Hill's Pet Nutrition, Inc. Companion animal compositions including lipoic acid and methods of use thereof
US8722112B2 (en) 2005-07-14 2014-05-13 Hill's Pet Nutrition, Inc. Method for prolonging the life of animals
US8846724B2 (en) 2003-12-29 2014-09-30 President And Fellows Of Harvard College Compositions for treating obesity and insulin resistance disorders
US9241916B2 (en) 2005-06-14 2016-01-26 President And Fellows Of Harvard College Cognitive performance with sirtuin activators

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WO2002009693A1 (en) * 2000-08-02 2002-02-07 Pharmanutrients Method and compositions for prevention and/or treatment of diabetes and glucose modulation
US20060062864A1 (en) * 2000-12-28 2006-03-23 Mccleary Edward L Weight loss composition and method
US20040043013A1 (en) 2000-12-28 2004-03-04 Mccleary Edward Larry Metabolic uncoupling therapy
US6964969B2 (en) 2001-04-19 2005-11-15 Mccleary Edward Larry Composition and method for treating impaired or deteriorating neurological function
US20060014773A1 (en) * 2001-04-19 2006-01-19 Mccleary Edward L Mental agility lozenge, edible strip, food or drink
WO2003079819A1 (en) * 2002-03-27 2003-10-02 Anglo French Drugs And Industries Ltd. Dietary supplement composition and a process of manufacturing said composition
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CA2284909A1 (en) 1998-09-24
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