Treatment for atherosclerosis and other cardiovascular and inflammatory diseases

• US 5,807,884 A
• Filed: 10/04/1994
• Issued: 09/15/1998
• Est. Priority Date: 10/30/1992
• Status: Expired due to Term

• Current Assignee: Emory University
• Original Assignee: Emory University
• Inventors: Parthasarathy, Sampath, Khan, Bobby V., Medford, Russell M., Alexander, R. Wayne
• Primary Examiner(s): O SULLIVAN, PETER G
• Application Number:
  US08/317,399
• Time in Patent Office: 1,442 Days
• Field of Search: 424/9.1, 424/9.2, 436/71, 436/86, 436/129, 514/18, 514/423, 514/478, 514/479, 514/484, 514/485, 514/487, 514/488, 514/489, 514/506, 514/513, 514/824, 514/825, 514/826, 514/861, 514/863, 514/226.2, 514/477 , 514/517, 514/518, 514/553, 514/561, 530/331, 548/431, 548/531, 558/230, 558/235, 558/234, 558/250, 564/76, 568/21, 568/25, 562/26, 562/27
• US Class Current: 514/423
• 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 31/145 having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) isothiourea A61K31/155
• CPC Class Codes: A61K 31/185 Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids hydroxamic acids A61K31/16; peroxy acids A61K31/327
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/265 of carbonic, thiocarbonic, or thiocarboxylic acids, e.g. thioacetic acid, xanthogenic acid, trithiocarbonic acid
• CPC Class Codes: A61K 31/325 Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof thiurams A61K31/145
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07C 333/04 having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 333/08 having nitrogen atoms of thiocarbamic groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07C 333/16 Salts of dithiocarbamic acids
• CPC Class Codes: C07D 295/21 Radicals derived from sulfur analogues of carbonic acid
• CPC Class Codes: G01N 2333/70503 : Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
• CPC Class Codes: G01N 2333/7056 : Selectin superfamily, e.g. LAM-1, GlyCAM, ELAM-1, PADGEM
• CPC Class Codes: G01N 2500/00 : Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 2800/323 : Arteriosclerosis, Stenosis
• CPC Class Codes: G01N 33/68 : involving proteins, peptides or amino acids involving lipoproteins G01N33/92
• CPC Class Codes: G01N 33/92 : involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743
• CPC Class Codes: Y10T 436/201666 : Carboxylic acid

Abstract

A method for the treatment of cardiovascular diseases and noncardiovascular inflammatory diseases that are mediated by VCAM-1 is provided that includes the removal, decrease in the concentration of, or prevention of the formation of oxidized polyunsaturated fatty acids, or interferes with a complex formed between a polyunsaturated fatty acid or an oxidized polyunsaturated fatty acid and a protein or peptide that mediates the expression of VCAM-1. A method is also provided for suppressing the expression of a redox-sensitive gene or activating a gene that is suppressed through a redox-sensitive pathway, that includes administering an effective amount of a substance that prevents the oxidation of the oxidized signal, and typically, the oxidation of a polyunsaturated fatty acid, or interferes with a complex formed between the oxidized signal and a protein or peptide that mediates the expression of the redox gene.

Claims

1. A method for supressing the expression of VCAM-1 comprising administering an effective amount of a substance that prevents or minimizes the oxidation of a polyunsaturated fatty acid.

2. The method of claim 1, wherein the polyunsaturated acid is selected from the group consisting of oxidized linoleic (C₁₈ Δ

⁹,12), linolenic (C₁₈ Δ

⁶,9,12), arachidonic (C₂₀ Δ

⁵,8,11,14) and eicosatrienoic (C₂₀ Δ

⁸,11,14).