WO2001003682B1 - Use of pyridoxin derivatives for the treatment of diabetes and related complications - Google Patents

Use of pyridoxin derivatives for the treatment of diabetes and related complications

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Publication number
WO2001003682B1
WO2001003682B1 PCT/IB2000/001041 IB0001041W WO0103682B1 WO 2001003682 B1 WO2001003682 B1 WO 2001003682B1 IB 0001041 W IB0001041 W IB 0001041W WO 0103682 B1 WO0103682 B1 WO 0103682B1
Authority
WO
WIPO (PCT)
Prior art keywords
group
carbon atoms
pyridoxal
analogue
acylated
Prior art date
Application number
PCT/IB2000/001041
Other languages
French (fr)
Other versions
WO2001003682A3 (en
WO2001003682A2 (en
Inventor
Rajat Sethi
Wasimul Haque
Original Assignee
Medicure Inc
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 Medicure Inc filed Critical Medicure Inc
Priority to EP00944170A priority Critical patent/EP1196171A2/en
Priority to CA002376029A priority patent/CA2376029A1/en
Priority to AU58402/00A priority patent/AU5840200A/en
Publication of WO2001003682A2 publication Critical patent/WO2001003682A2/en
Publication of WO2001003682A3 publication Critical patent/WO2001003682A3/en
Publication of WO2001003682B1 publication Critical patent/WO2001003682B1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4355—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • 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
    • A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • 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

Abstract

Methods for treating diabetes mellitus and related conditions and symptoms are described. The methods are directed to administering a therapeutically effective amount of a compound. Compounds suitable for the invention include pyridoxal-5'-phosphate, pyridoxal, pyridoxamine, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, or a mixture thereof. Also disclosed are methods directed to concurrently administering a therapeutically effective amount of a compound with other compounds known in the treatment of diabetes mellitus. In one embodiment, a therapeutically effective amount of a compound is administered concurrently with a therapeutically effective amount of insulin. In another embodiment, a therapeutically effective amount of a compound is administered concurrently with a therapeutically effective amount of a hypoglycemic compound.

Claims

AMENDED CLAIMS[received by the International Bureau on 12 September 2001 (12.09.01); original claims 1-75 replaced by amended claims 1-15 (3 pages)]
1. Use of pyridoxal-5 '-phosphate, pyridoxamine, pyridoxal, pyidoxine, a 3- acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, or a mixture thereof for preparation of a medicament for treating insulin-dependent or non-insulin-dependent diabetes mellitus and related conditions and symptoms in a mammal comprising: administering to the mammal a therapeutically effective amount of pyridoxal-5 '-phosphate, pyridoxamine, pyridoxal, pyidoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, or a mixture thereof.
2. The use of claim 1, wherein the 3-acylated pyridoxal analogue is a compound of the formula
Figure imgf000002_0001
wherein
Ri is a straight or branched alkyl group of 1 to 8 carbon atoms, a straight or branched alkenyl group of 2 to 8 carbon atoms, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group of 1 to 4 carbon atoms; a dialkylamino group; an unsubstituted aryl group; or an aryl substituted with an alkyl of 1 to 4 carbon atoms, an alkoxy of 1 to 4 carbon atoms, a hydroxy, an amino, or an acetyloxy group.
3. The use of claim 1, wherein the 3-acylated pyridoxal analogue is 2-methyl-3- toluoyloxy-4-formyl-5-hydroxymethylpyridine.
4. The use of claim 1, wherein the 3-acylated pyridoxal analogue is 2-methyl-3- ? -naphthoyloxy-4-formyl-5-hydroxymethylpyridine.
42
A Er,DED SHEET (ARTICLE 19)
5. The use of claim 1 , wherein the 3-acylated pyridoxal analogue is a compound of the formula
Figure imgf000003_0001
II wherein
Ri is a straight or branched alkyl group of 1 to 8 carbon atoms, a straight or branched alkenyl group of 2 to 8 carbon atoms, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group of 1 to 4 carbon atoms; a dialkylamino group; an unsubstituted aryl group; or an aryl substituted with an alkyl of 1 to 4 carbon atoms, an alkoxy of 1 to 4 carbon atoms, a hydroxy, an amino, or an acetyloxy group; and
R.2 is a secondary amino group of the formula
R ^K.
N-
Ri wherein R3 and R4 are each independently alkyl of one to 8 carbon atoms or when taken together form a ring with the nitrogen atom and which ring may optionally be interrupted by a nitrogen or oxygen atom.
6. The use of claim 2 or 5, wherein Ri is phenyl or naphthyl in which phenyl or naphthyl is unsubstituted or substituted by an alkyl group of 1 to 4 carbon atoms, an alkoxy group of 1 to 4 carbon atoms, an amino group, a hydroxy group, or an acetyloxy group.
7. The use of claim 5, wherein the 3-acylated pyridoxal analogue is 1- morpholino-l,3-dihydro-7-(p-toluoyloxy)-6-methylfuro(3,4-c)pyridine.
8. The use of claim 5, wherein the 3-acylated pyridoxal analogue is 1- morpholino-l,3-dihydro-7-(β-naphthoyloxy)-6-methylfuro(3,4-c)pyridine.
9. The use of claim 5, wherein the 3-acylated pyridoxal analogue is 1- morpholino- 1 ,3 -dihydro-7-pivaloyloxy-6-methylfuro(3 ,4-c)pyridine.
10. The use of claim 5, wherein the 3-acylated pyridoxal analogue is 1- morpholino-l,3-dihydro-7-(dimethylcarbamoyloxy-6-methylfuro(3,4-c)pyridine.
11. The use of claim 5, wherein the 3-acylated pyridoxal analogue is 1 - morpholino- 1 ,3-dihydro-7-acetylsalicyloxy-6-methylfuro(3 ,4-c)pyridine.
12. The use of claim 1, further comprising concurrently administering to the mammal a therapeutically effective amount of insulin, a hypoglycemic compound, or a combination thereof.
13. The use of claim 12, wherein the hypoglycemic compound is metformin, acarbose, acetohexamide, glimepiride, tolazamide, glipizide, glyburide, tolbutamide, chlorpropamide, thiazolidinediones, alpha glucosidase inhibitors, biguanindine derivatives, and troglitazone, or a mixture thereof.
14. The use of claim 1, wherein insulin-dependent or non- insulin-dependent diabetes mellitus and related conditions and symptoms include diabetes mellitus type I, diabetes mellitus type II, obesity, insulin resistance, hyperinsulinemia, diabetes- induced hypertension, and diabetes-related damage to blood vessels, eyes, kidneys, nerves, autonomic nervous system, skin, connective tissue, or immune system.
15. The use of claim 1 , wherein the therapeutically effective amount is in a range of about 0.5 -100 mg/kg of the mammal's body weight per day.
PCT/IB2000/001041 1999-07-13 2000-07-13 Use of pyridoxin derivatives for the treatment of diabetes and related complications WO2001003682A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP00944170A EP1196171A2 (en) 1999-07-13 2000-07-13 Use of pyridoxin derivatives for the treatment of diabetes and related complications
CA002376029A CA2376029A1 (en) 1999-07-13 2000-07-13 Use of pyridoxin derivatives for the treatment of diabetes and related complications
AU58402/00A AU5840200A (en) 1999-07-13 2000-07-13 Treatment of diabetes and related pathologies

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14346699P 1999-07-13 1999-07-13
US60/143,466 1999-07-13

Publications (3)

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WO2001003682A3 WO2001003682A3 (en) 2001-12-27
WO2001003682B1 true WO2001003682B1 (en) 2002-01-24

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US (4) US6489345B1 (en)
EP (1) EP1196171A2 (en)
AU (1) AU5840200A (en)
CA (1) CA2376029A1 (en)
WO (1) WO2001003682A2 (en)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6750209B1 (en) * 1995-09-12 2004-06-15 Kansas University Medical Center Advanced glycation end-product intermediaries and post-amadori inhibition
WO2001003682A2 (en) * 1999-07-13 2001-01-18 Medicure Inc. Use of pyridoxin derivatives for the treatment of diabetes and related complications
US7442689B2 (en) * 2000-02-29 2008-10-28 Medicure International Inc. Cardioprotective phosphonates and malonates
US6897228B2 (en) 2000-07-07 2005-05-24 Medicure International Inc. Pyridoxine and pyridoxal analogues: new uses
CA2520422A1 (en) * 2003-03-27 2004-10-07 Medicure Inc. Compositions for treating angina
AU2004224562A1 (en) * 2003-03-27 2004-10-07 Medicure Inc. Modulation of cell death
US20090082407A1 (en) * 2004-06-18 2009-03-26 Biostratum, Inc. Pyridoxamine for the Treatment of Diabetic Kidney Disease
US20050014799A1 (en) * 2003-06-20 2005-01-20 Biostratum, Inc. Pyridoxamine for the treatment of diabetic kidney disease
US20050054731A1 (en) * 2003-09-08 2005-03-10 Franco Folli Multi-system therapy for diabetes, the metabolic syndrome and obesity
US7214799B2 (en) * 2004-02-09 2007-05-08 Biostratum, Inc. Methods for the synthesis of pyridoxamine
WO2006005173A1 (en) * 2004-07-09 2006-01-19 Medicure International Inc. Combination therapies employing nicotinic acid derivatives or fibric acid derivatives
EP2248531A1 (en) * 2004-08-03 2010-11-10 Emisphere Technologies, Inc. Antidiabetic oral insulin-biguanide combination
WO2006015489A1 (en) * 2004-08-10 2006-02-16 Medicure International Inc. Combination therapies employing vitamin b6 related compounds and ace inhibitors and uses thereof for the treatment of diabetic disorders
US20070060549A1 (en) * 2004-08-10 2007-03-15 Friesen Albert D Combination therapies employing ace inhibitors and uses thereof for the treatment of diabetic disorders
US7459468B2 (en) 2004-10-28 2008-12-02 Medicure International, Inc. Aryl sulfonic pyridoxines as antiplatelet agents
CA2585165A1 (en) 2004-10-28 2006-05-18 Medicure International Inc. Dual antiplatelet/anticoagulant pyridoxine analogs
WO2006056079A1 (en) * 2004-11-26 2006-06-01 Medicure International Inc. Formulations of pyridoxal -5'-phosphate and methods of preparation
CA2528191A1 (en) * 2004-11-26 2006-05-26 Medicure International Inc. Novel formulation of pyridoxal 5'-phosphate and method of preparation
CA2593793A1 (en) * 2005-01-05 2006-07-13 Medicure International Inc. Compounds and methods for regulating triglyceride levels
CA2503087A1 (en) * 2005-03-30 2006-09-30 Medicure International Inc. Intravenous formulations of pyridoxal 5'-phosphate and method of preparation
CA2614664A1 (en) * 2005-07-14 2007-01-25 Franco Folli Daily dosage regimen for treating diabetes, obesity,metabolic syndrome and polycystic ovary syndrome
WO2007121588A1 (en) * 2006-04-25 2007-11-01 Medicure International Inc. Treatment of atrial fibrillation

Family Cites Families (126)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3206463A (en) 1965-09-14 Pyridoxine aspartate and its process of preparation
FR846376A (en) 1938-08-23 1939-09-15 Air navigation and aerial bombardment equipment
US3282778A (en) * 1960-09-02 1966-11-01 Lohel Mervyn Joseph Medicinal preparation containing acetyl salicylic acid and a pyridoxine compound
GB966805A (en) 1961-05-15 1964-08-19 Merck & Co Inc Process for the preparation of 2-methyl-3-hydroxypyridines
NL280553A (en) 1962-07-05
GB1228142A (en) 1967-03-31 1971-04-15
ES367284A1 (en) 1968-05-16 1971-04-01 Merck Ag E Storage-stable vitamin preparations
ES360566A1 (en) 1968-11-22 1970-10-16 Made Labor Sa Pyridoxine alpha-ketoglutarate and derivatives thereof
GB1236531A (en) 1969-02-12 1971-06-23 Soc D Etudes Prod Chimique Adenin derivative
US3910921A (en) 1970-01-08 1975-10-07 Soc D Etudes Prod Chimique Papaverine monopyridoxal phosphate
GB1297080A (en) 1970-04-17 1972-11-22
FR2101010A1 (en) 1970-08-06 1972-03-31 Lyocentre Sparteine mono-and dipyridoxinates and prepn - as tonics for cardiova disorders
GB1493993A (en) 1975-05-16 1977-12-07 Howard A Dietary supplement and dietary methods employing said supplement for the treatment of obesity
US4053607A (en) 1972-04-04 1977-10-11 Beecham Group Limited Aryloxypyridine for treating hyperglycaemia
US4036844A (en) 1972-04-04 1977-07-19 Beecham Group Limited Aryloxypyridines
GB1360536A (en) 1972-04-25 1974-07-17 Soc D Etudes Prod Chimique Pyridoxyl-l-aspartic acid salt
BE790118A (en) 1972-10-09 1973-02-01 Made Labor Sa PYRIDOXAL AND PYRIDOXAMINE ALPHA-CETOGLUTARATE DERIVATIVES,
US4032534A (en) 1973-03-22 1977-06-28 Ferlus-Chimie S.A. Certain 2-(2-thioethyl)thiazolidine-4-carboxylic acids
FR2255883A1 (en) 1973-12-28 1975-07-25 Centre Etd Ind Pharma Clofibric acid-vitamin B6 compsns. - with synergistic hypocholesterolaemic and normolipaemic activity
FR2275209A1 (en) 1974-06-21 1976-01-16 Synthelabo Oxoalkyl esters of vincamine acids - and their pharm. acceptable salts for use in medicine
FR2276048A1 (en) 1974-06-27 1976-01-23 Synthelabo NEW CYCLOHEXANOL ESTERS, THEIR SALTS, THEIR PREPARATION AND THE MEDICINAL PRODUCTS CONTAINING THEM
DE2461742C2 (en) 1974-12-28 1983-01-27 Steigerwald Arzneimittelwerk Gmbh, 6100 Darmstadt Pyridoxine-5'-phosphoric acid ester derivatives and their preparation and pharmaceuticals containing these compounds
GB1525885A (en) 1976-05-11 1978-09-20 Soc D Etudes Prod Chimique Vincamine salt of pyridoxal phosphate
DE2717478C2 (en) 1977-04-20 1984-08-16 Basf Ag, 6700 Ludwigshafen Process for the preparation of pyridoxine
JPS5417130A (en) 1977-07-08 1979-02-08 Chugai Pharmaceut Co Ltd Remedy for cardio-vasocular diseases
BE863754A (en) 1978-02-08 1978-05-29 Dechamps Pierre NEW VINCAMINE DERIVATIVES FOR USE AS BRAIN CIRCULATION REGULATORS
FR2428640A1 (en) 1978-06-12 1980-01-11 Parcor 5-Piperazino:alkoxy:methyl-pyridine cpds. - with antiinflammatory, diuretic and vaso-protective properties
US4167562A (en) 1978-08-28 1979-09-11 Evers H Ray Method and composition for treating arteriosclerosis
IL62602A (en) 1980-05-19 1984-06-29 Labaz Sanofi Nv Pyridoxine derivatives,their preparation and pharmaceutical compositions containing them
IT1141070B (en) 1980-09-22 1986-10-01 Luso Farmaco Inst USE OF ALPHA-KETOGLUTARATE OF PYRIDOXY IN THE PROPHYLAXIS OF HYPERLACTACIDEMIA
CA1184499A (en) 1981-06-29 1985-03-26 David C. Madsen Nutritional composition for management of hepatic failure
US4369172A (en) 1981-12-18 1983-01-18 Forest Laboratories Inc. Prolonged release therapeutic compositions based on hydroxypropylmethylcellulose
US4528197A (en) 1983-01-26 1985-07-09 Kabivitrum Ab Controlled triglyceride nutrition for hypercatabolic mammals
IN160104B (en) 1983-04-05 1987-06-27 Scras
US4735950A (en) 1983-04-05 1988-04-05 Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S) Furo-(3,4-C)-pyridine derivatives and therapeutic composition containing the same
US4515771A (en) 1983-04-11 1985-05-07 Fine Daniel H Composition and method for the preventative treatment of dental disease and apparatus for dispensing said composition
US4513771A (en) * 1983-11-07 1985-04-30 General Motors Corporation Air valve
GB8330517D0 (en) 1983-11-16 1983-12-21 Scras 6-vinyl-furo-(3,4-c)pyridine derivatives
GB8330658D0 (en) 1983-11-17 1983-12-29 Scras 7-carboxymethoxy-furo-(3,4-c)-pyridine derivatives
IT1212792B (en) 1983-11-30 1989-11-30 Egidio Aldo Moja DIETARY SUPPLEMENT AND PRE-PACKED FOOD THAT CONTAINS IT PREPARATION PROCEDURE AND METHOD OF ADMINISTRATION
US5130324A (en) 1984-03-19 1992-07-14 The Rockefeller University 2-alkylidene-aminoguanidines and methods of use therefor
US5272165A (en) 1984-03-19 1993-12-21 The Rockefeller University 2-alkylidene-aminoguanidines and methods of use therefor
US4567179A (en) 1984-10-11 1986-01-28 Pfizer, Inc. Antiinflammatory salts of piroxicam
DE3519693A1 (en) 1985-06-01 1987-01-02 Basf Ag PYRIDINE DERIVATIVES, THEIR PRODUCTION AND USE
US4837239A (en) 1985-08-23 1989-06-06 Syntex (U.S.A.) Inc. Cardiotonic phosphodiesterase inhibitors complexed with water soluble vitamins
US5053396A (en) 1985-08-27 1991-10-01 Blass David H Therapeutic composition
US4735956A (en) 1985-09-13 1988-04-05 Merck & Co., Inc. Certain 1,4-dihydro-2,6-di-lower hydrocarbyl-4-heterocyclic-3,5-pyridine dicarboxylates which are useful as calcium channel blockers
US4605741A (en) 1985-11-13 1986-08-12 Lisapharma Spa Pharmaceutically active salt derivative of 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde phosphate
DE3634016A1 (en) 1986-04-17 1987-10-29 Lohmann Gmbh & Co Kg AREA-BASED THERAPEUTIC SYSTEM, METHOD FOR THE PRODUCTION THEREOF AND ITS USE
US5210083A (en) 1986-07-17 1993-05-11 Ed. Geistlich Sohne A.G. Fur Chemische Industrie Pharmaceutical compositions
US5563126A (en) 1986-11-20 1996-10-08 Metabolite Laboratories Method for treatment and prevention of deficiencies of vitamins B12, folic acid, and B6
NZ222664A (en) 1986-11-29 1990-06-26 Vesta Med Pty Ltd Pharmaceutical compositions containing pyridoxal as a source of vitamin b6
US5254572A (en) 1987-11-27 1993-10-19 Vesta Medicines (Pty) Ltd. Method and composition for supplementing vitamin B6 where the PN-PLP pathway is disturbed
US5631271A (en) 1986-11-29 1997-05-20 Serfontein; Willem J. Methods and preparations for the treatment and prophylaxis of metabolic disturbances
US4843071A (en) 1986-12-05 1989-06-27 Serotonin Industries Of Charleston Method and composition for treating obesity, drug abuse, and narcolepsy
US5288716A (en) 1987-02-18 1994-02-22 Ulrich Speck Use of pyridoxine derivatives in the prevention and treatment of hyperlipidaemia and atherosclerosis
DE3705549A1 (en) 1987-02-18 1988-09-01 Ulrich Speck USE OF PYRIDOXINE DERIVATIVES IN THE PROPHYLAXIS AND THERAPY OF HYPERLIPIDAEMIA AND ATHEROSCLEROSIS
SE8701662L (en) 1987-04-22 1988-10-23 Gelder Nico M Van SETTING AND AGENTS FOR TREATING NEUROLOGICAL DISEASES, EXAMPLE, MIGRAEN THROUGH THE OPERATION OF NERV CELLS
US5213813A (en) 1987-05-29 1993-05-25 The University Of Vermont Pyridoxal-5'-phosphate as an in vitro blood platelet stabilizer
DE58902094D1 (en) 1988-01-28 1992-10-01 Koeltringer Peter COMBINATION DEVICE FOR THE TREATMENT OF NERVOUS AND NERVE FIBER DISEASES AND INJURIES.
NO179479C (en) 1988-03-11 1996-10-16 Teikoku Seiyaku Kk Process for the preparation of an intravaginal pharmaceutical preparation
US5254557A (en) 1988-05-09 1993-10-19 Beecham Group P.L.C. Compound and treatment
FR2641189B1 (en) 1988-06-20 1991-05-10 Timol Mamoojee PHARMACEUTICAL COMPOSITIONS CONTAINING ACETYL SALICYLIC ACID AND VITAMIN B6
US5088977A (en) 1988-12-21 1992-02-18 Drug Delivery Systems Inc. Electrical transdermal drug applicator with counteractor and method of drug delivery
US5001115A (en) 1989-05-17 1991-03-19 University Of Florida Prodrugs of biologically active hydroxyaromatic compounds
GB8918368D0 (en) 1989-08-11 1989-09-20 Amco Chemie Gmbh Compositions for treating obstructive airways disease
DE4016963A1 (en) 1990-05-25 1991-11-28 Steigerwald Arzneimittelwerk USE OF MAGNESIUM PYRIDOXAL 5'-PHOSPHATE GLUTAMINATE TO PREVENT ILLNESSES ARISING AS A RESULT OF DISSOLUTION
US5385937A (en) 1991-04-10 1995-01-31 Brigham & Women's Hospital Nitrosation of homocysteine as a method for treating homocysteinemia
GB2254556B (en) 1991-04-11 1995-04-12 Fisons Plc Formulations containing linolenic acid
CA2103050A1 (en) 1991-05-15 1992-11-16 Yung-Chi Cheng Determination of prodrugs metabolizable by the liver and therapeutic use thereof
FR2678622B1 (en) 1991-07-03 1994-11-18 Adir NEW VANADIUM COMPLEXES, THEIR PREPARATION PROCESS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.
CA2125888C (en) 1992-01-06 2002-08-27 Harry B. Demopoulos Pharmaceutically active antioxidant containing composition and the method of its use to prevent and treat restenosis following angioplasty
US5420112A (en) 1992-06-12 1995-05-30 Lewis; Michael E. Prevention and treatment of peripheral neuropathy
AU683215B2 (en) 1992-06-12 1997-11-06 Albert Einstein College Of Medicine Of Yeshiva University Prevention and treatment of peripheral neuropathy
US5330743A (en) 1992-11-12 1994-07-19 Magnetic Research, Inc. Aminosaccharide contrast agents for magnetic resonance images
US5795873A (en) 1992-12-29 1998-08-18 Metabolite Laboratories, Inc. Method for treatment and prevention of deficiencies of vitamins B12, folic acid and B6
IT1263957B (en) 1993-02-23 1996-09-05 THERAPEUTIC USE OF PYROLIDON CARBOXYLATE OF PYRIDOXY
TW268948B (en) 1993-04-02 1996-01-21 Senju Pharma Co
DE4344751A1 (en) 1993-12-28 1995-06-29 Carl Heinrich Dr Weischer New vitamin=B6 ester cpds. of sulphur-contg. carboxylic acids
US5504090A (en) 1994-03-30 1996-04-02 Trustees Of The University Of Pennsylvania Compositions and methods for the prevention and treatment of ischemia-reperfusion organ injury
ES2244966T3 (en) 1994-12-12 2005-12-16 Omeros Corporation IRRIGATION SOLUTION AND ITS USE TO PERIOPERATORY INHIBIT THE PAIN, INFLAMMATION AND SPASM IN A WOUND.
US5569459A (en) 1995-02-15 1996-10-29 Bio-Virus Research Incorporated Pharmaceutical compositions for the management of premenstrual syndrome and alleviation of menopausal disorders
US5733916A (en) 1995-03-24 1998-03-31 The Trustees Of The University Of Pennsylvania Prevention and treatment of ischemia-reperfusion and endotoxin-related injury using adenosine and purino receptor antagonists
US6228858B1 (en) * 1995-09-12 2001-05-08 University Of Kansas Medical Center Advanced glycation end-product intermediaries and post-amadori inhibition
US5744451A (en) * 1995-09-12 1998-04-28 Warner-Lambert Company N-substituted glutamic acid derivatives with interleukin-1 β converting enzyme inhibitory activity
US5874443A (en) 1995-10-19 1999-02-23 Trega Biosciences, Inc. Isoquinoline derivatives and isoquinoline combinatorial libraries
US5833998A (en) 1995-11-06 1998-11-10 The Procter & Gamble Company Topical compositions for regulating the oily/shiny appearance of skin
US5733884A (en) 1995-11-07 1998-03-31 Nestec Ltd. Enteral formulation designed for optimized wound healing
US5874420A (en) 1995-12-26 1999-02-23 Allegheny University Of The Health Sciences Process for regulating vagal tone
US5847008A (en) 1996-02-02 1998-12-08 Merck & Co., Inc. Method of treating diabetes and related disease states
US5859051A (en) 1996-02-02 1999-01-12 Merck & Co., Inc. Antidiabetic agents
US5834446A (en) 1996-06-21 1998-11-10 Queen's University At Kingston Nerve process growth modulators
US7030146B2 (en) * 1996-09-10 2006-04-18 University Of South Carolina Methods for treating diabetic neuropathy
US5770215A (en) 1997-01-06 1998-06-23 Moshyedi; Emil Payman Multivitamin/vascular occlusion inhibiting composition
US5804594A (en) 1997-01-22 1998-09-08 Murad; Howard Pharmaceutical compositions and methods for improving wrinkles and other skin conditions
US5888514A (en) 1997-05-23 1999-03-30 Weisman; Bernard Natural composition for treating bone or joint inflammation
EP0891719A1 (en) 1997-07-14 1999-01-20 N.V. Nutricia Nutritional composition containing methionine
US6051587A (en) * 1998-04-16 2000-04-18 Medicure, Inc. Treatment of iatrogenic and age-related hypertension and pharmaceutical compositions useful therein
US6103748A (en) * 1998-06-19 2000-08-15 Bryan; Thomas B. Method of treating an autoimmune disorder
US6043259A (en) * 1998-07-09 2000-03-28 Medicure Inc. Treatment of cardiovascular and related pathologies
AU3512400A (en) * 1999-03-05 2000-09-21 Kansas University Medical Center Novel post-amadori inhibitors of advanced glycation reactions
JP2002539127A (en) * 1999-03-08 2002-11-19 メディキュア インコーポレーテッド Pyridoxal analogs for vitamin B-6 disorders
SE516023C2 (en) * 1999-06-24 2001-11-12 Abb Ab Industrial robot comprising an gearbox configuration and method in an industrial robot
AU777997B2 (en) * 1999-07-09 2004-11-11 Oregon Health And Science University Compositions and methods for promoting nerve regeneration
WO2001003682A2 (en) * 1999-07-13 2001-01-18 Medicure Inc. Use of pyridoxin derivatives for the treatment of diabetes and related complications
JP2003507418A (en) * 1999-08-24 2003-02-25 メディキュア インターナショナル インコーポレイテッド Treatment of cardiovascular disease and related diseases
PT1268498E (en) * 2000-02-29 2005-07-29 Medicure Int Inc CARDIOPROTECTOR PHOSPHONATES
US7442689B2 (en) * 2000-02-29 2008-10-28 Medicure International Inc. Cardioprotective phosphonates and malonates
WO2001072309A2 (en) * 2000-03-28 2001-10-04 Medicure International Inc. Treatment of cerebrovascular disease
US6548519B1 (en) * 2001-07-06 2003-04-15 Medicure International Inc. Pyridoxine and pyridoxal analogues: novel uses
EP1299358B1 (en) * 2000-07-07 2007-06-13 Medicure International Inc. Pyridoxine and pyridoxal analogues as cardiovascular therapeutics
US6897228B2 (en) * 2000-07-07 2005-05-24 Medicure International Inc. Pyridoxine and pyridoxal analogues: new uses
US20040121988A1 (en) * 2001-03-28 2004-06-24 Medicure International Inc. Treatment of cerebrovascular disease
US20040186077A1 (en) * 2003-03-17 2004-09-23 Medicure International Inc. Novel heteroaryl phosphonates as cardioprotective agents
CA2520422A1 (en) * 2003-03-27 2004-10-07 Medicure Inc. Compositions for treating angina
AU2004224562A1 (en) * 2003-03-27 2004-10-07 Medicure Inc. Modulation of cell death
CA2570048A1 (en) * 2004-07-07 2006-01-12 Medicure International Inc. Combination therapies employing platelet aggregation drugs
WO2006015489A1 (en) * 2004-08-10 2006-02-16 Medicure International Inc. Combination therapies employing vitamin b6 related compounds and ace inhibitors and uses thereof for the treatment of diabetic disorders
US20070060549A1 (en) * 2004-08-10 2007-03-15 Friesen Albert D Combination therapies employing ace inhibitors and uses thereof for the treatment of diabetic disorders
US20060094749A1 (en) * 2004-10-28 2006-05-04 Medicure International Inc. Substituted pyridoxines as anti-platelet agents
US7459468B2 (en) * 2004-10-28 2008-12-02 Medicure International, Inc. Aryl sulfonic pyridoxines as antiplatelet agents
CA2585165A1 (en) * 2004-10-28 2006-05-18 Medicure International Inc. Dual antiplatelet/anticoagulant pyridoxine analogs
CA2528191A1 (en) * 2004-11-26 2006-05-26 Medicure International Inc. Novel formulation of pyridoxal 5'-phosphate and method of preparation
CA2593793A1 (en) * 2005-01-05 2006-07-13 Medicure International Inc. Compounds and methods for regulating triglyceride levels
WO2007059631A1 (en) * 2005-11-28 2007-05-31 Medicure International Inc. Selected dosage for the treatment of cardiovascular and related pathologies
WO2007121588A1 (en) * 2006-04-25 2007-11-01 Medicure International Inc. Treatment of atrial fibrillation

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WO2001003682A3 (en) 2001-12-27
US6489345B1 (en) 2002-12-03
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