Free radical quenching composition and a method to increase intracellular and/or extracellular antioxidants

• US 6,764,693 B1
• Filed: 12/11/1992
• Issued: 07/20/2004
• Est. Priority Date: 12/11/1992
• Status: Expired due to Fees

• Current Assignee: Amaox Incorporated
• Original Assignee: Amaox Incorporated
• Inventors: Smith, Milton G.
• Primary Examiner(s): Page, Thurman K.
• Application Number:
  US07/989,593
• Time in Patent Office: 4,239 Days
• Field of Search: 424/450, 424/2.2, 424/702, 424/45, 424/641, 424/422, 424/630, 424/434, 424/626, 424/400, 514/356, 514/458, 514/474, 514/725
• US Class Current: 424/450
• 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 2800/522 Antioxidants; Radical scavengers
• CPC Class Codes: A61K 31/015 carbocyclic
• CPC Class Codes: A61K 31/355 Tocopherols, e.g. vitamin E
• CPC Class Codes: A61K 31/375 Ascorbic acid, i.e. vitamin C; Salts thereof
• CPC Class Codes: A61K 31/455 Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
• CPC Class Codes: A61K 33/06 Aluminium, calcium or magnesium; Compounds thereof , e.g. clay
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/30 Zinc; Compounds thereof
• CPC Class Codes: A61K 33/32 Manganese; Compounds thereof
• CPC Class Codes: A61K 33/34 Copper; Compounds thereof
• CPC Class Codes: A61K 38/063 Glutathione
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 8/14 Liposomes; Vesicles
• CPC Class Codes: A61K 8/19 containing inorganic ingredients
• CPC Class Codes: A61K 8/23 Sulfur; Selenium; Tellurium; Compounds thereof
• CPC Class Codes: A61K 8/27 Zinc; Compounds thereof
• CPC Class Codes: A61K 8/31 Hydrocarbons
• CPC Class Codes: A61K 8/64 Proteins; Peptides; Derivatives or degradation products thereof
• CPC Class Codes: A61K 8/675 Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde tocopheryl nicotinate A61K8/678
• CPC Class Codes: A61K 8/676 : Ascorbic acid, i.e. vitamin C
• CPC Class Codes: A61K 8/678 : Tocopherol, i.e. vitamin E
• CPC Class Codes: A61K 9/127 : Liposomes
• 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: A61Q 17/00 : Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings

Abstract

A free radical quenching composition is disclosed comprising a liposome containing at least two antioxidants selected from the following group: beta-carotene, vitamin E, vitamin C, glutathione, niacin, and optionally at least one trace metal (Zn, Se, Cr, Cu, Mn). Also disclosed is a method for reducing the undesirable side effects of free radicals in a mammal by administering to a mammal in need of such antioxidants an effective amount of liposomes containing at least two antioxidants.

Claims

1. A method of preventing or treating a disease or an injury induced by pathological free radical reactions, the method comprising administering to the mammal an effective amount of an antioxidant composition comprising:

(i) a population of liposomes suitable for undergoing peroxidation and lysis; and

(ii) at least two non-enzymatic amphipathic antioxidants selected from the group consisting of;

beta-carotene, vitamin E, vitamin C, glutathione, niacin, and N-acetyl-cysteine, in an amount of sufficient to deliver 0.005-1.0 g beta-carotene per kg body weight, 0.001-10 g vitamin E per kg body weight, 0.001-2.0 g vitamin C per kg body, 0.001-2.0 g glutathione per kg body weight, 1-1000 mg niacin per kg body weight and 0.003-6.0 g N-acetyl-cysteine per kg body weight,

wherein the disease or injury is selected from the group consisting of;

acute respiratory distress syndrome, ischemia-reperfusion injury, hemorrhagic shock, tissue injury induced by inflammation, and tissue injury induced by a chemical agent or a caustic agent, and wherein the amphipathic antioxidant composition quenches free radicals and reduces the damage induced by the pathological free radical reactions.

2. The method of claim 1, wherein said composition further comprises at least one trace metal.

3. The method of claim 2, wherein said at least one trace metal is selected from the group consisting of zinc, selenium, chromium, copper and manganese.

4. The method of claim 1, wherein said composition further comprises a pharmaceutically acceptable carrier.

5. The method of claim 1, wherein said composition is administered by a route of administration selected from the group consisting of:

intravenous, intraperitoneal, subcutaneous, intramuscular, intraarticular, intraarterial, intracerebral, intracerebellar, intrabronchial, intrathecal, topical, and aerosol route.

6. The method according to claim 2, wherein the composition includes an amount of trace metals sufficient to deliver 1-1000 μ

g trace metals per day.

7. A method for alleviating the deleterious effects of pathological free radical reactions in a mammal afflicted with a disease or an injury induced by pathological free radical reactions, the method comprising administering an effective amount of an antioxidant composition comprising:

(i) a population of liposomes suitable for undergoing peroxidation and lysis; and

(ii) at least two non-enzymatic amphipathic antioxidants selected from the group consisting of;

beta-carotene, vitamin E, vitamin C, glutathione, niacin, and N-acetyl-cysteine, in an amount of sufficient to deliver 0.0005-1.0 g beta-carotene per kg body weight, 0.001-10 g vitamin E per kg body weight, 0.001-2.0 g vitamin C per kg body, 0.001-2.0 g glutathione per kg body weight, 1-1000 mg niacin per kg body weight and 0.003-6.0 g N-acetyl-cysteine per kg body weight,

wherein the disease or injury is selected from the group consisting of;

acute respiratory distress syndrome, ischemia-reperfusion injury, hemorrhagic shock, tissue injury induced by inflammation, and tissue injury induced by a chemical agent or a caustic agent, and wherein the amphipathic antioxidant composition quenches free radicals and reduces the damage induced by the pathological free radical reactions.

8. The method of claim 7, wherein said composition further comprises at least one trace metal.

9. The method of claim 8, wherein said at least one trace metal is selected from the group consisting of zinc, selenium, chromium, copper and manganese.

10. The method of claim 7, wherein said composition further comprises a pharmaceutically acceptable carrier.

11. The method of claim 7, wherein said composition is administered by a route of administration selected from the group consisting of:

intravenous, intraperitoneal, subcutaneous, intramuscular, intraarticular, intraarterial, intracerebral, intracerebellar, intrabronchial, intrathecal, topical, and aerosol route.

12. The method according to claim 7, wherein the composition includes an amount of trace metals sufficient to deliver 1-1000 μ

g trace metal per day.