Treatment of conditions and disease

• US 5,852,002 A
• Filed: 06/05/1995
• Issued: 12/22/1998
• Est. Priority Date: 09/21/1989
• Status: Expired due to Term

• Current Assignee: Hyal Pharmaceutical Corporation (Scully Royalty Ltd.)
• Original Assignee: Hyal Pharmaceutical Corporation (Scully Royalty Ltd.)
• Inventors: Asculai, Samuel S., Falk, Rudolf Edgar
• Primary Examiner(s): PESELEV, ELLI
• Application Number:
  US08/462,147
• Time in Patent Office: 1,296 Days
• Field of Search: 514/54, 536/55.1, 536/55.3
• US Class Current: 514/54
• 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 31/10 Sulfides; Sulfoxides; Sulfones
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/375 Ascorbic acid, i.e. vitamin C; Salts thereof
• 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 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/503 spiro-condensed
• CPC Class Codes: A61K 31/54 having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/61 : the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 9/0014 : Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0019 : Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 11/08 : Bronchodilators
• 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 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 5/24 : of the sex hormones
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

A combination for administration to a mammal which combination employs a therapeutically effective amount of a medicinal and/or therapeutic agent to treat a disease or condition and an amount of hyaluronic acid and/or salts thereof and/or homologues, analogues, derivatives, complexes, esters, fragments and subunits of hyaluronic acid sufficient to facilitate the agent'"'"'s penetration through the tissue (including scar tissue) at the site to be treated, through the cell membranes into the individual cells to be treated.

Claims

1. A method of treating a condition or disease in a human involving tissue selected from the group consisting of underperfused tissue and pathological tissue which will benefit from the treatment by the administration of an agent selected from the group consisting of a medicinal agent and a therapeutic agent and combinations thereof, which is suitable for treating said tissue, the method comprising administering to the human a therapeutically effective dosage amount of a pharmaceutical composition comprising a therapeutically effective amount of the agent to treat the disease or condition involving tissue selected from the group consisting of underperfused tissue and pathological tissue, and a sufficient amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and its non-toxic salts and combinations thereof sufficient to facilitate the transport and penetration of the agent through the tissue at a site to be treated through the cell membranes into the individual cells to be treated wherein the molecular weight of the form of hyaluronic acid is in the range of 150,000 to 750,000 daltons, and said amount of the form of hyaluronic acid is sufficient to provide a dosage greater than 10 mg and less than 3000 mg.

2. A dosage amount of a pharmaceutical composition in a suitable pharmaceutically acceptable excipient for treating infection involving underperfused tissue and pathological tissue in humans, said dosage amount comprising a therapeutically effective amount of an agent selected from the group consisting of antibiotics, antibacterials, antimicrobials and combinations thereof with or without ascorbic acid and a sufficient amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and its non-toxic salts and combinations thereof to facilitate the transport of the agent at a site to be treated by the agents passing through the tissue through the cell membranes into the individual cells to be treated wherein the molecular weight of the form of hyaluronic acid is in the range of 150,000 to 750,000 daltons, and said amount of the form of hyaluronic acid is sufficient to provide a dosage greater than 10 mg.

3. The dosage amount of claim 2 wherein the form of hyaluronic acid is sodium hyaluronate.

4. A dosage amount of a pharmaceutical composition in a suitable pharmaceutically acceptable excipient for treating infections surrounding implants involving underperfused tissue and pathological tissue in a patient, said dosage amount comprising a therapeutically effective amount of an antibiotic agent for treating the infected tissue surrounding the implant and a sufficient amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and its non-toxic salts and combinations thereof to facilitate the transport and penetration of the agent at a site to be treated by the agents passing through the tissue through the cell membranes into the individual cells to be treated wherein the molecular weight of the form of hyaluronic acid is in the range of 150,000 to 750,000 daltons, and said amount of the form of hyaluronic acid is sufficient to provide a dosage greater than 10 mg. and less than 3000 mg.

5. A method of treating infection involving underperfused tissue and pathological tissue in humans, the method comprising the administration of a therapeutically effective amount of an agent selected from the group consisting of antibiotics, antibacterials, antimicrobials and combinations thereof with or without ascorbic acid and a sufficient amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and its non-toxic salts and combinations thereof to facilitate the transport and penetration of the agent at a site to be treated by the agents passing through the tissue through the cell membranes into the individual cells to be treated wherein the molecular weight of the form of hyaluronic acid is in the range of 150,000 to 750,000 daltons, and said amount of the form of hyaluronic acid is sufficient to provide a dosage greater than 10 mg and less than 3000 mg.

6. A method of treating infections surrounding implants involving underperfused tissue and pathological tissue in a patient, the method comprising the administration of a therapeutically effective amount of an antibiotic for the infected tissue surrounding the implant and a sufficient amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and its non-toxic salts and combinations thereof to facilitate the transport and penetration of the agent at a site to be treated by the agents passing through the tissue through the cell membranes into the individual cells to be treated wherein the molecular weight of the form of hyaluronic acid is in the range of 150,000 to 750,000 daltons, and said amount of the form of hyaluronic acid is sufficient to provide a dosage greater than 10 mg and less than 3000 mg.

7. The method of claim 6 wherein the form of hyaluronic acid is sodium hyaluronate.

8. A dosage amount of a pharmaceutical composition in a suitable pharmaceutically acceptable excipient for the prevention of topical infection involving underperfused tissue and pathological tissue in humans, said dosage amount comprising an effective amount of an anti-metabolite agent for preventing topical infection and a sufficient amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and its non-toxic salts and combinations thereof to facilitate the transport and penetration of the agent at a site to be treated by the agents passing through the tissue through the cell membranes into the individual cells to be treated wherein the molecular weight of the form of hyaluronic acid is in the range of 150,000 to 750,000 daltons, and said amount of the form of hyaluronic acid is sufficient to provide a dosage greater than 10 mg and less than 3000 mg.

9. The dosage amount of claim 8 wherein the form of hyaluronic acid is sodium hyaluronate.

10. A method of (preventing) treating a topical infection resulting from a condition or disease in a human involving underperfused tissue and pathological tissue in humans, the method comprising the administration of an effective amount of an anti-metabolite agent and a sufficient amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and its non-toxic salts and combinations thereof to facilitate the transport and penetration of the agent at a site to be treated by the agents passing through the tissue through the cell membranes into the individual cells to be treated wherein the molecular weight of the form of hyaluronic acid is in the range of 150,000 to 750,000 daltons, and said amount of the form of hyaluronic acid is sufficient to provide a dosage greater than 10 mg and less than 3000 mg.

11. The method of claim 10 wherein the form of hyaluronic acid is sodium hyaluronate.