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WO1997035576A1 - Utilisation de l'isoniazide pour le traitement de l'hyperlipoproteinemie - Google Patents

Utilisation de l'isoniazide pour le traitement de l'hyperlipoproteinemie Download PDF

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Publication number
WO1997035576A1
WO1997035576A1 PCT/IL1997/000085 IL9700085W WO9735576A1 WO 1997035576 A1 WO1997035576 A1 WO 1997035576A1 IL 9700085 W IL9700085 W IL 9700085W WO 9735576 A1 WO9735576 A1 WO 9735576A1
Authority
WO
WIPO (PCT)
Prior art keywords
isoniazid
plasma
mammal
hdl cholesterol
concentration
Prior art date
Application number
PCT/IL1997/000085
Other languages
English (en)
Inventor
Arie Roth
Shlomo Laniado
Naftali Stern
Abraham Man
Original Assignee
Tel-Aviv Medical Center Research And Development Fund
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 Tel-Aviv Medical Center Research And Development Fund filed Critical Tel-Aviv Medical Center Research And Development Fund
Priority to AU22282/97A priority Critical patent/AU2228297A/en
Publication of WO1997035576A1 publication Critical patent/WO1997035576A1/fr

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Classifications

    • 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
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides

Definitions

  • the present invention relates to the use of a known drug for the prevention and treatment of hyperlipoproteinemia which can lead to heart disease.
  • Hyperlipoproteinemia is a condition in which the concentration of cholesterol- and/or triacylglycerol-carrying lipoproteins in the plasma exceeds a well defined normal limit. Clinical concern arises because an elevated concentration of lipoproteins can accelerate the development of atherosclerosis, thrombosis and infarction. Numerous population studies have shown that elevated serum concentration of total cholesterol, and especially low-density lipoprotein (LDL)-cholesterol, constitutes a major risk factor for the occurrence of atherosclerotic events. It has been clearly demonstrated that lowering the concentration of cholesterol-carrying lipoproteins in plasma can diminish the risk of myocardial infarction.
  • LDL low-density lipoprotein
  • HDL high- density lipoprotein
  • Fibric Acids Aryloxyisobutyric acids and other related compounds collectively referred to as fibric acids have been found to be effective in reducing plasma concentrations of triglycerides and LDL-cholesterol. Some of these drugs have also been shown to mildly increase HDL-cholesterol. Among the better known compounds are: clofibrate, gemfibrozil, feno- fibrate, ciprofibrate, benzafibrate.
  • HMG (hydroxymethylglutaric acid) CoA reductase inhibitors These drugs, which are fungal-derived compounds, were found effective in lowering LDL-cholesterol and generally result in a mild increase in HDL- cholesterol. Compounds include: mevastatin, lovastatin, simvastatin, pravastatin.
  • Nicotinic Acid This drug decreases plasma triglycerides, LDL- cholesterol and induce a mild to moderate increase in HDL-cholesterol, but its use is limited by the frequent occurrence of serious side effects.
  • Isoniazid also known as isonicotinic acid hydrazide (INH)
  • Isoniazid is considered to be a primary drug for the chemotherapy of tuberculosis (Goodman and Gilman, supra, pages 1146-1149).
  • Other minor therapeutic uses which have been described for this drug include cerebellar tremor, Crohn's Disease, Huntington's Disease, Parkinson's Disease, Multiple Sclerosis and shoulder-hand syndrome.
  • cerebellar tremor Crohn's Disease
  • Huntington's Disease Huntington's Disease
  • Parkinson's Disease Multiple Sclerosis and shoulder-hand syndrome.
  • its precise anti-tuberculous mechanism is unknown, it was observed to act on the same hepatic enzymes as does alcohol. The latter has been shown to have the capability of increasing plasma HDL-cholesterol. - 3 -
  • the anti-tuberculosis drug isoniazid is active in increasing the HDL cholesterol concentration in the plasma. According to one aspect of the present invention, there is provided a method for decreasing the LDL/HDL cholesterol ratio in the plasma of a mammal comprising administering isoniazid to the mammal.
  • isoniazid is administered in combination with a hypolipidemic drug.
  • the combination of the two drugs results in a lowering of the LDL/HDL ratio and enables utilizing lower doses of each of the individual drugs, thus minimizing drug specific side effects.
  • Tabie II LDL-Cholesterol (mg/dl)
  • the ratio can be further decreased by administering a hypolipidemic drug, which decreases the concentration of LDL cholesterol, in combination with isoniazid.
  • a hypolipidemic drug which decreases the concentration of LDL cholesterol, in combination with isoniazid.
  • drugs include fibric acids such as clofibrate, gem- fibrozil, fenofibrate, ciprofibrate and bezafibrate; HMG CoA reductase inhibitors such as mevastatin, lovastatin, simvastatin and pravastatin; and nicotinic acid.
  • a pharmaceutical composition can be prepared for decreasing the LDL/HDL cholesterol ratio in the plasma of a mammal which comprises isoniazid together with a pharmaceutically acceptable excipient.
  • excipients include for example amylan, acacia, tragacanth, sodium stearate glycolate, elcema, talc and calcium stearate.
  • various hypolipidemic drugs can be included in the composition.
  • the composition is preferably in an oral form. Typical doses of isoniazid are in the range of 10-300 mg accumulated dose. In the event that isoniazid is administered together with hypolipidemic drugs, the dose can be reduced.
  • isoniazid in the treatment of hyperlipoproteinemia can provide a major contribution to the primary and secondary (post cardiovas ⁇ cular event) prevention of cardiovascular events, including myocardial infarction, cerebrovascular disease and peripheral vascular disease.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Il s'est avéré, d'une manière tout à fait inattendue, que l'isoniazide (hydrazide de l'acide isonicotinique ou INH), qui est connu comme médicament contre la tuberculose, est également utile pour traiter l'hyperlipoprotéinémie. L'invention concerne une méthode permettant de diminuer le rapport cholestérol des lipoprotéines basse densité sur cholestérol des lipoprotéines haute densité (LDL/HDL) dans le plasma d'un mammifère en lui administrant de l'isoniazide. L'isoniazide peut être administré avec d'autres médicaments connus capables d'abaisser la concentration en lipoprotéines plasmiques, pour améliorer l'effet. On décrit également une composition pharmaceutique contenant de l'isoniazide.
PCT/IL1997/000085 1996-03-28 1997-03-10 Utilisation de l'isoniazide pour le traitement de l'hyperlipoproteinemie WO1997035576A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU22282/97A AU2228297A (en) 1996-03-28 1997-03-10 Use of isoniazid for the treatment of hyperlipoproteinemia

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IL117702 1996-03-28
IL11770296A IL117702A0 (en) 1996-03-28 1996-03-28 Drug for hyperlipoproteinemia

Publications (1)

Publication Number Publication Date
WO1997035576A1 true WO1997035576A1 (fr) 1997-10-02

Family

ID=11068709

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IL1997/000085 WO1997035576A1 (fr) 1996-03-28 1997-03-10 Utilisation de l'isoniazide pour le traitement de l'hyperlipoproteinemie

Country Status (3)

Country Link
AU (1) AU2228297A (fr)
IL (1) IL117702A0 (fr)
WO (1) WO1997035576A1 (fr)

Cited By (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000018395A1 (fr) * 1998-09-30 2000-04-06 Warner-Lambert Company Procede pour empecher ou retarder la revascularisation par catheter
US6264960B1 (en) 1998-11-10 2001-07-24 Sander J. Robins Treatment of vascular events using lipid-modifying compositions
US6982251B2 (en) 2000-12-20 2006-01-03 Schering Corporation Substituted 2-azetidinones useful as hypocholesterolemic agents
US6984645B2 (en) 2001-11-16 2006-01-10 Bristol-Myers Squibb Company Dual inhibitors of adipocyte fatty acid binding protein and keratinocyte fatty acid binding protein
WO2006019886A2 (fr) 2004-07-14 2006-02-23 Bristol-Myers Squibb Company Pyrrolo(oxo)isoquinoleines utilisees comme ligands 5ht
US7030106B2 (en) 2001-01-26 2006-04-18 Schering Corporation Sterol absorption inhibitor compositions
US7053080B2 (en) 2001-09-21 2006-05-30 Schering Corporation Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors
US7056906B2 (en) 2001-09-21 2006-06-06 Schering Corporation Combinations of hormone replacement therapy composition(s) and sterol absorption inhibitor(s) and treatments for vascular conditions in post-menopausal women
US7071181B2 (en) 2001-01-26 2006-07-04 Schering Corporation Methods and therapeutic combinations for the treatment of diabetes using sterol absorption inhibitors
US7132415B2 (en) 2001-09-21 2006-11-07 Schering Corporation Methods and therapeutic combinations for the treatment of xanthoma using sterol absorption inhibitors
US7192944B2 (en) 2003-03-07 2007-03-20 Schering Corp. Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7208486B2 (en) 2003-03-07 2007-04-24 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7220859B2 (en) 2005-01-12 2007-05-22 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid receptor modulators
US7235543B2 (en) 2003-03-07 2007-06-26 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7238702B2 (en) 2005-02-10 2007-07-03 Bristol-Myers Squibb Company Dihydroquinazolinones as 5HT modulators
US7314882B2 (en) 2005-01-12 2008-01-01 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid receptor modulators
US7317012B2 (en) 2005-06-17 2008-01-08 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoind-1 receptor modulators
US7368458B2 (en) 2005-01-12 2008-05-06 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid receptor modulators
US7371759B2 (en) 2003-09-25 2008-05-13 Bristol-Myers Squibb Company HMG-CoA reductase inhibitors and method
US7417039B2 (en) 2001-01-26 2008-08-26 Schering Corporation Use of substituted azetidinone compounds for the treatment of sitosterolemia
US7420059B2 (en) 2003-11-20 2008-09-02 Bristol-Myers Squibb Company HMG-CoA reductase inhibitors and method
US7452892B2 (en) 2005-06-17 2008-11-18 Bristol-Myers Squibb Company Triazolopyrimidine cannabinoid receptor 1 antagonists
US7459442B2 (en) 2003-03-07 2008-12-02 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7517991B2 (en) 2004-10-12 2009-04-14 Bristol-Myers Squibb Company N-sulfonylpiperidine cannabinoid receptor 1 antagonists
US7553836B2 (en) 2006-02-06 2009-06-30 Bristol-Myers Squibb Company Melanin concentrating hormone receptor-1 antagonists
US7560449B2 (en) 2002-11-06 2009-07-14 Schering Corporation Methods and therapeutic combinations for the treatment of demyelination
US7572808B2 (en) 2005-06-17 2009-08-11 Bristol-Myers Squibb Company Triazolopyridine cannabinoid receptor 1 antagonists
US7629342B2 (en) 2005-06-17 2009-12-08 Bristol-Myers Squibb Company Azabicyclic heterocycles as cannabinoid receptor modulators
US7632837B2 (en) 2005-06-17 2009-12-15 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid-1 receptor modulators
US7709647B2 (en) 2005-01-18 2010-05-04 Bristol-Myers Squibb Company Tetrahydroquinoline cannabinoid receptor modulators
US7795436B2 (en) 2005-08-24 2010-09-14 Bristol-Myers Squibb Company Substituted tricyclic heterocycles as serotonin receptor agonists and antagonists
WO2010111665A1 (fr) 2009-03-27 2010-09-30 Bristol-Myers Squibb Company Procédés destinés à prévenir des événements cardiovasculaires indésirables majeurs par des inhibiteurs de la dpp-iv
EP2298776A1 (fr) 2005-10-26 2011-03-23 Bristol-Myers Squibb Company Dérivés du thienopyrimidinone comme antagonistes d'hormone 1 de concentration de mélanine
US7989433B2 (en) 2008-05-29 2011-08-02 Bristol-Myers Squibb Company Substituted thieno[3,2-D]pyrimidines as melanin concentrating hormone receptor-1 antagonists
WO2014039412A1 (fr) 2012-09-05 2014-03-13 Bristol-Myers Squibb Company Antagonistes du récepteur 1 d'hormone concentrant la mélanine de type pyrrolone ou pyrrolidinone
US9586900B2 (en) 2012-09-05 2017-03-07 Bristol-Myers Squibb Company Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
JAMES E. E. REYNOLDS: "MARTINDALE THE EXTRA PHARMACOPOEIA", 1993, THE PHARMACEUTICAL PRESS, LONDON, XP002032798 *
KARTHIKEYAN, S. ET AL: "Effect of subacute administration of isoniazid and pyridoxine on lipids in plasma, liver and adipose tissues in the rabbit", DRUG CHEM. TOXICOL. (1977) (1991), 14(3), 293-303 CODEN: DCTODJ;ISSN: 0148-0545, 1991, XP002032797 *
KUTTY, K. M. ET AL: "Serum cholinesterase activity in hyperlipidemia and the in vitro effect of isoniazid on serum cholinesterase", CAN. J. BIOCHEM. (1972), 50(1), 32-4 CODEN: CJBIAE, 1972, XP000654503 *

Cited By (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000018395A1 (fr) * 1998-09-30 2000-04-06 Warner-Lambert Company Procede pour empecher ou retarder la revascularisation par catheter
EA007427B1 (ru) * 1998-09-30 2006-10-27 Варнер Ламберт Компани Способ предотвращения или отсрочки катетерной реваскуляризации
US6264960B1 (en) 1998-11-10 2001-07-24 Sander J. Robins Treatment of vascular events using lipid-modifying compositions
US6982251B2 (en) 2000-12-20 2006-01-03 Schering Corporation Substituted 2-azetidinones useful as hypocholesterolemic agents
US7071181B2 (en) 2001-01-26 2006-07-04 Schering Corporation Methods and therapeutic combinations for the treatment of diabetes using sterol absorption inhibitors
US7612058B2 (en) 2001-01-26 2009-11-03 Schering Corporation Methods for inhibiting sterol absorption
US7030106B2 (en) 2001-01-26 2006-04-18 Schering Corporation Sterol absorption inhibitor compositions
US7417039B2 (en) 2001-01-26 2008-08-26 Schering Corporation Use of substituted azetidinone compounds for the treatment of sitosterolemia
US7132415B2 (en) 2001-09-21 2006-11-07 Schering Corporation Methods and therapeutic combinations for the treatment of xanthoma using sterol absorption inhibitors
US7056906B2 (en) 2001-09-21 2006-06-06 Schering Corporation Combinations of hormone replacement therapy composition(s) and sterol absorption inhibitor(s) and treatments for vascular conditions in post-menopausal women
US7053080B2 (en) 2001-09-21 2006-05-30 Schering Corporation Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors
US6984645B2 (en) 2001-11-16 2006-01-10 Bristol-Myers Squibb Company Dual inhibitors of adipocyte fatty acid binding protein and keratinocyte fatty acid binding protein
US7560449B2 (en) 2002-11-06 2009-07-14 Schering Corporation Methods and therapeutic combinations for the treatment of demyelination
US7368562B2 (en) 2003-03-07 2008-05-06 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7192944B2 (en) 2003-03-07 2007-03-20 Schering Corp. Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7208486B2 (en) 2003-03-07 2007-04-24 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7235543B2 (en) 2003-03-07 2007-06-26 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7459442B2 (en) 2003-03-07 2008-12-02 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7378518B2 (en) 2003-03-07 2008-05-27 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7368563B2 (en) 2003-03-07 2008-05-06 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7371759B2 (en) 2003-09-25 2008-05-13 Bristol-Myers Squibb Company HMG-CoA reductase inhibitors and method
US7420059B2 (en) 2003-11-20 2008-09-02 Bristol-Myers Squibb Company HMG-CoA reductase inhibitors and method
WO2006019886A2 (fr) 2004-07-14 2006-02-23 Bristol-Myers Squibb Company Pyrrolo(oxo)isoquinoleines utilisees comme ligands 5ht
US7517991B2 (en) 2004-10-12 2009-04-14 Bristol-Myers Squibb Company N-sulfonylpiperidine cannabinoid receptor 1 antagonists
US7220859B2 (en) 2005-01-12 2007-05-22 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid receptor modulators
US7361766B2 (en) 2005-01-12 2008-04-22 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid receptor modulators
US7314882B2 (en) 2005-01-12 2008-01-01 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid receptor modulators
US7368458B2 (en) 2005-01-12 2008-05-06 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid receptor modulators
US7709647B2 (en) 2005-01-18 2010-05-04 Bristol-Myers Squibb Company Tetrahydroquinoline cannabinoid receptor modulators
US7238702B2 (en) 2005-02-10 2007-07-03 Bristol-Myers Squibb Company Dihydroquinazolinones as 5HT modulators
US7629342B2 (en) 2005-06-17 2009-12-08 Bristol-Myers Squibb Company Azabicyclic heterocycles as cannabinoid receptor modulators
US7452892B2 (en) 2005-06-17 2008-11-18 Bristol-Myers Squibb Company Triazolopyrimidine cannabinoid receptor 1 antagonists
US7632837B2 (en) 2005-06-17 2009-12-15 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid-1 receptor modulators
US7317012B2 (en) 2005-06-17 2008-01-08 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoind-1 receptor modulators
US7572808B2 (en) 2005-06-17 2009-08-11 Bristol-Myers Squibb Company Triazolopyridine cannabinoid receptor 1 antagonists
US7858639B2 (en) 2005-06-17 2010-12-28 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid-1 receptor modulators
US7795436B2 (en) 2005-08-24 2010-09-14 Bristol-Myers Squibb Company Substituted tricyclic heterocycles as serotonin receptor agonists and antagonists
EP2298776A1 (fr) 2005-10-26 2011-03-23 Bristol-Myers Squibb Company Dérivés du thienopyrimidinone comme antagonistes d'hormone 1 de concentration de mélanine
US8618115B2 (en) 2005-10-26 2013-12-31 Bristol-Myers Squibb Company Substituted thieno[3,2-d]pyrimidinones as MCHR1 antagonists and methods for using them
US7956049B2 (en) 2006-02-06 2011-06-07 Bristol-Myers Squibb Company Melanin concentrating hormone receptor-1 antagonists
US7553836B2 (en) 2006-02-06 2009-06-30 Bristol-Myers Squibb Company Melanin concentrating hormone receptor-1 antagonists
US7989433B2 (en) 2008-05-29 2011-08-02 Bristol-Myers Squibb Company Substituted thieno[3,2-D]pyrimidines as melanin concentrating hormone receptor-1 antagonists
WO2010111665A1 (fr) 2009-03-27 2010-09-30 Bristol-Myers Squibb Company Procédés destinés à prévenir des événements cardiovasculaires indésirables majeurs par des inhibiteurs de la dpp-iv
WO2014039412A1 (fr) 2012-09-05 2014-03-13 Bristol-Myers Squibb Company Antagonistes du récepteur 1 d'hormone concentrant la mélanine de type pyrrolone ou pyrrolidinone
US9499482B2 (en) 2012-09-05 2016-11-22 Bristol-Myers Squibb Company Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
US9586900B2 (en) 2012-09-05 2017-03-07 Bristol-Myers Squibb Company Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists

Also Published As

Publication number Publication date
IL117702A0 (en) 1996-07-23
AU2228297A (en) 1997-10-17

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