Pharmaceutical preparations and medicaments for the prevention and treatment of endothelial dysfunction

• US 5,973,011 A
• Filed: 09/27/1996
• Issued: 10/26/1999
• Est. Priority Date: 03/30/1994
• Status: Expired due to Fees

• Current Assignee: Isis Pharma GmbH (Zoetis, Inc.)
• Original Assignee: Isis Pharma GmbH (Zoetis, Inc.)
• Inventors: Kojda, Georg, Noack, Eike Albrecht
• Primary Examiner(s): Criares, Theodore J.
• Application Number:
  US08/721,465
• Time in Patent Office: 1,124 Days
• Field of Search: 514/642, 514/742, 514/645, 514/350, 514/711, 514/740, 514/464
• US Class Current: 514/742
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/21 Esters, e.g. nitroglycerine, selenocyanates
• CPC Class Codes: A61K 31/34 having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
• CPC Class Codes: A61K 31/4406 only substituted in position 3, e.g. zimeldine nicotinic acid A61K31/455
• CPC Class Codes: A61K 38/55 Protease inhibitors
• CPC Class Codes: A61K 38/556 Angiotensin converting enzyme inhibitors
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

The present invention describes the use of nitric-oxide-liberating or transferring compounds, stimulators of endogenous NO formation, as well as stimulators of guanylate cyclase, for prevention, treatment and elimination of endothelial dysfunctions and the diseases accompanying these dysfunctions or caused by them, as well as the use of said compounds to produce pharmaceutical products for the cited areas of application.

Claims

1. A method of treating endothelial dysfunctions caused by hypercholesterolemia,

said method comprising administration of 6 mg/kg/day of an organic nitrate to an individual to maintain or improve endothelial function.

2. The method of claim 1 wherein the organic nitrate is selected from the group consisting of glycerol trinitrate, pentaerythrityl tetranitrate, isosorbide-5-mononitrate, isosorbide dinitrate;

mannitol hexanitrate, inositol hexanitrate, propatyl nitrate, trolnitrate, nicorandil or SPM 3672, and pharmacologically compatible derivatives.

3. The method of claim 1 wherein the organic nitrate is used in pharmaceutical preparations for treating endothelial dysfunctions.

4. The method of claim 3 wherein the organic nitrate is combined with active compounds used to treat cardiovascular diseases.

5. The method of claim 4 wherein the active compound to treat cardiovascular diseases is selected from the group consisting of ACE inhibitors, antiatherosclerotics, antihypertensives, beta-blockers, cholesterol reducers, diuretics, calcium antagonists, coronary dilators, lipid reducers, peripheral vasodilators and thrombocyte aggregation inhibitors.

6. The method of claim 2 wherein the organic nitrate comprises pentaerythrityl tetranitrate (PETN).

7. A method of treating endothelial damage attributed to hypercholesterolemia comprising administration of a 6 mg/kg/day an organic nitrate to an individual to maintain or improve endothelial function.