Treatment of basal cell carcinoma and actinic keratosis employing hyaluronic acid and NSAIDs

• US 5,639,738 A
• Filed: 02/21/1992
• Issued: 06/17/1997
• Est. Priority Date: 02/20/1992
• Status: Expired due to Term

• Current Assignee: Hyal Pharmaceutical Corporation (Scully Royalty Ltd.), Jagotec Ag (Vectura Group Ltd.)
• Original Assignee: Hyal Pharmaceutical Corporation (Scully Royalty Ltd.)
• Inventors: Falk, Rudolf Edgar, Asculai, Samuel Simon
• Primary Examiner(s): Kight, John
• Assistant Examiner(s): Fonda, Kathleen Kahler
• Application Number:
  US07/838,675
• Time in Patent Office: 1,943 Days
• Field of Search: 514/23, 514/54, 514/62, 536/55.2, 536/88, 536/123
• 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 31/19 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 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• 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 31/455 Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
• CPC Class Codes: A61K 31/503 spiro-condensed
• 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 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• 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 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• 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

Abstract

A method of treating a mammal for a condition of the skin or exposed tissue selected from the group consisting of basal cell carcinoma and actinic keratosis is provided. The method consists essentially of topically administering to the site of the condition, more than once per day over a period of days sufficient to treat the condition, a non-toxic effective dosage amount of a composition consisting essentially of

(a) a non-steroidal anti-inflammatory drug (NSAID) in an amount sufficient to block prostaglandin synthesis,

(b) hyaluronic acid or a pharmaceutically acceptable salt thereof in an amount effective to transport said NSAID into the skin or exposed tissue at the site of the condition. The concentration of the hyaluronic add or salt thereof is between 1-3% by weight of the composition. The molecular weight of the hyaluronic acid or salt thereof is between 150,000 and 750,000 Daltons. A pharmaceutical excipient suitable for topical application is included. The NSAID in the composition may be diclofenac sodium.

Claims

1. A method of treating a mammal for a condition of the skin or exposed tissue selected from the group consisting of basal cell carcinoma and actinic keratosis, which method consists essentially of topically administering to the site of the condition, more than once per day over a period of days sufficient to treat the condition, a non-toxic effective dosage amount of a composition consisting essentially of

(a) a non-steroidal anti-inflammatory drug (NSAID) in an amount sufficient to block prostaglandin synthesis,

(b) hyaluronic acid or a pharmaceutically acceptable salt thereof in an amount effective to transport said NSAID into the skin or exposed tissue at the site of the condition, wherein the concentration of the hyaluronic acid or salt thereof is between 1-3% by weight of the composition, and the molecular weight of the hyaluronic acid or salt thereof is between 150,000 and 750,000 Daltons, and

(c) a pharmaceutical excipient suitable for topical application.

2. The method of claim 1 wherein the treatment is applied for a period of weeks.

3. The method of claim 1 or 2 wherein the concentration of the NSAID is between 1-5% by weight of the composition.

4. The method of claim 1 or 2 wherein the NSAID is selected from the group consisting of diclofenac, diclofenac sodium, indomethacin, naproxen. (+±

) tromethamine salt of ketorolac, ibuprofen, piroxicam, acetylsalicylic acid and flunixin and wherein the concentration of the NSAID is between 1%-5% by weight of the composition.

5. The method of claim 1 or 2 wherein the concentration of hyaluronic acid or salt thereof is 21/2% by weight of the composition and the concentration of NSAID is 3% by weight of the composition.

6. The method of claim 1 or 2 wherein the hyaluronic acid or salt thereof is sodium hyaluronate and is in the concentration of 21/2% by weight of the dosage amount and the NSAID is diclofenac sodium and is in the concentration of 3% by weight of the dosage amount.

7. A method of treating a mammal for a condition of the skin or exposed tissue selected from the group consisting of basal cell carcinoma and actinic keratosis, which method consists essentially of topically administering to the site of the condition, more than once per day over a period of days sufficient to treat the condition, a non-toxic effective dosage amount of a composition consisting essentially of

(a) a non-steroidal anti-inflammatory drug (NSAID) in an amount sufficient to block prostaglandin synthesis, wherein the concentration of the NSAID between 1-5% by weight of the composition,

(b) hyaluronic acid or a pharmaceutically acceptable salt thereof in an amount effective to transport said NSAID into the skin or exposed tissue at the site of the condition, wherein the concentration of the hyaluronic acid or salt thereof is between 1-3% by weight of the composition, and the molecular weight of the hyaluronic acid or salt thereof is between 150,000 and 750,000 Daltons, and

(c) a pharmaceutical excipient suitable for topical application.

8. The method of claim 7 wherein the treatment is applied for a period of weeks.

9. The method of claim 7 or 8 wherein the NSAID is selected for the group consisting of diclofenac, diclofenac sodium, indomethacin, naproxen, (+±

) tromethamine salt of ketorolac, ibuprofen, piroxicam, acetylsalicylic acid and flunixin.

10. The method of claim 7 or 8 wherein the hyaluronic acid or salt thereof is sodium hyaluronate in a concentration of 21/2% by weight of the composition and the NSAID is diclofenac sodium and is in the concentration of 3% by weight of the dosage amount.

11. A method of treating a mammal for actinic keratosis of the skin or exposed tissue, which method consists essentially of topically administering to the site of the actinic keratosis, more than once per day over a period of days sufficient to treat the actinic keratosis, a non-toxic effective dosage amount of a composition consisting essentially of

(a) a non-steroidal anti-inflammatory drug (NSAID) in an amount sufficient to block prostaglandin synthesis;

(b) hyaluronic acid or a pharmaceutically acceptable salt thereof in an amount effective to transport said NSAID into the skin or exposed tissue at the site of the actinic keratosis, wherein the concentration of the hyaluronic acid or salt thereof is between 1-3% by weight of the composition, and the molecular weight of the hyaluronic acid or salt thereof is between 150,000 and 750,000 Daltons, and

(c) a pharmaceutical excipient suitable for topical application.

12. The method of claim 11 wherein the treatment is applied for a period of weeks.

13. The method of claim 12 wherein the percent of the NSAID in the composition is between 1-5% by weight of the composition.

14. The method of claim 11, 12, or 13 wherein the NSAID is selected from the group consisting of diclofenac, diclofenac sodium, indomethacin, naproxen, (+±

) tromethamine salt of ketorolac, ibuprofen, piroxicam, acetylsalicylic acid and flunixin.

15. The method of claim 11 wherein the hyaluronic acid or salt thereof is sodium hyaluronate having a molecular weight between 150,000 daltons and, 750,000 daltons and is in the concentration of 21/2% by weight of the composition and the NSAID is diclofenac sodium and is in the concentration of 3% by weight of the composition.

16. The method of claim 15 wherein the pharmaceutical excipient comprises an effective amount of a solubilizer for the diclofenac sodium.

17. The method of claim 16 wherein the solubilizer is methoxypolyethylene glycol.

18. The method of claim 15 wherein the pharmaceutical excipient comprises sterile water and an effective solubilizing amount of methoxypolyethylene glycol 350 for the diclofenac sodium.