Details for Patent: 6,114,314

Title:	Formulations containing hyaluronic acid
Abstract:	Topically applied transdermally quick penetrating (best targeting the epidermis and subsequently remaining there for a prolonged period of time) systemic independent acting, combinations and formulations which employ, combine, or incorporate a therapeutically effective non-toxic (to the patient) amount of a drug which inhibits prostaglandin synthesis together with an amount of hyaluronic acid and/or salts thereof (for example the sodium salt) and/or homologues, analogues, derivatives, complexes, esters, fragments, and/or sub units of hyaluronic acid to treat a disease and condition of the skin and exposed tissue for example, basal cell carcinoma, the precancerous, often recurrent, actinic keratoses lesions, fungal lesions, "liver" spots and like lesions (found for the most part in the epidermis), squamous cell tumours, metastatic cancer of the breast to the skin, primary and metastatic melanoma in the skin, genital warts cervical cancer, and HPV (Human Papilloma Virus) including HPV of the cervix, psoriasis (both plaque-type psoriasis and nail bed psoriasis), corns on the feet and hair loss on the head of pregnant women and remain in the skin for a prolonged period of time.
Inventor(s):	Falk; Rudolf Edgar (Toronto, CA), Asculai; Samuel Simon (Toronto, CA), Klein; Ehud Shmuel (Givat Savyon, IL), Harper; David W. (Oakville, CA), Hochman; David (Thornhill, CA), Purschke; Don (Toronto, CA)
Assignee:	Hyal Pharmaceutical Corp. (CA)
Filing Date:	Dec 01, 1994
Application Number:	08/352,697
Claims:	1. A method of accumulating a drug and a form of hyaluronic acid in the skin or exposed tissue comprising topically administering a dosage of a pharmaceutical composition comprising together with pharmaceutical excipients suitable for topical application, a therapeutically effective, to treat and resolve a disease or condition of the skin and exposed tissue selected from the group consisting of basal cell carcinoma and actinic keratoses and pain, non-toxic amount of a drug and an effective non-toxic dosage amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and pharmaceutically acceptable salts thereof sufficient to facilitate the drug's quick penetration to the site in the skin or tissue of the disease or condition to accumulate and remain in the epidermis for a prolonged period of time wherein the percentage of the dosage of the form of the hyaluronic acid is between 1-3% by weight of the dosage and has a molecular weight less than 750,000 daltons but greater than 150,000 daltons and the percent of the drug of the composition is between 1-5% by weight of the dosage. 2. The method of claim 1 where the accumulation takes place in the epidermis. 3. The method of claim 1 or 2 wherein the form of hyaluronic acid is sodium hyaluronate. 4. A method of quickly delivering a drug to the epidermis and maintaining the drug therein for a prolonged period of time, the method comprising topically administering a dosage of a pharmaceutical composition comprising together with pharmaceutical excipients suitable for topical application, a therapeutically effective, to treat and resolve a disease a condition of the skin and exposed tissue selected from the group consisting of basal cell carcinoma and actinic keratoses, non-toxic amount of a drug which blocks prostaglandin synthesis and an amount of a form of hyaluronic acid selected from hyaluronic acid and pharmaceutically acceptable salts thereof sufficient to facilitate the drug's quick penetration to the site in the skin or tissue of the disease or condition through the tissue to accumulate and remain in the epidermis for a prolonged period of time to block prostaglandin synthesis wherein the percentage of the dosage of the form of the hyaluronic acid is between 1-3% by weight of the dosage and has a molecular weight less than 750,000 daltons but greater than 150,000 daltons and the percent of the drug of the composition is between 1-5% by weight of the dosage. 5. The method of claim 4, wherein accumulation takes place in the epidermis. 6. The method of claim 4 wherein the form of hyaluronic acid is sodium hyaluronate. 7. The method of claim 6 wherein the drug is a non-steroidal anti-inflammatory drug (NSAID). 8. The method of claim 7 wherein the NSAID is selected from diclofenac, indomethacin, naproxen, and (+,-) tromethamine salt of ketorolac. 9. The method of claim 7 wherein the NSAID is selected from Ibuprofen piroxicam, acetylsalicylic acid, propionic acid derivatives and flunixin. 10. A method of controlling the unloading of a drug from the skin or exposed tissue of a human suffering trauma or pathology into the lymphatic system comprising transporting into the skin or exposed tissue an amount of a drug by an effective non-toxic dosage amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and pharmaceutically acceptable salts thereof wherein the percentage of the dosage of the form of hyaluronic acid is between 1-3% by weight and has a molecular weight less than 750,000 daltons but greater than 150,000 daltons and the percent of the drug is between 1-5% by weight. 11. The method of claim 10 wherein the form of hyaluronic acid is sodium hyaluronate. 12. The method of claim 11 wherein the drug is a drug which inhibits prostaglandin synthesis. 13. The method of claim 12 wherein the drug is a non-steroidal anti-inflammatory drug (NSAID). 14. The method of claim 13 wherein the NSAID is selected from the group consisting of diclofenac, indomethacin, naproxen, (+,-) tromethamine salt of ketorolac, Ibuprofen, piroxicam, acetylsalicylic acid, propionic acid derivatives and flunixin. 15. A method of accumulating a drug in the skin or exposed tissue or both comprising topically administering to the skin or exposed tissue or both, a pharmaceutical composition comprising the drug and a form of hyaluronic acid, the amount of the composition administered comprising an effective non-toxic amount of the drug and an effective non-toxic amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and pharmaceutically acceptable salts thereof to transport or facilitate or cause the transport of the drug into the skin or exposed tissue to accumulate in the epidermis wherein the percent of the form of hyaluronic acid is 1-3% by weight of the composition and has a molecular weight less than 750,000 daltons but greater than 150,000 daltons and the percent of the drug is between 1-5% by weight. 16. The method of claim 15 wherein the form of hyaluronic acid is sodium hyaluronate. 17. The method of claim 16 wherein the drug is a drug which inhibits prostaglandin synthesis. 18. The method of claim 17 wherein the drug is a non-steroidal anti-inflammatory drug (NSAID). 19. The method of claim 18 wherein the NSAID is selected from the group consisting of diclofenac, indomethacin, naproxen, (+,-) tromethamine salt of ketorolac, Ibuprofen, piroxicam, acetylsalicylic acid, propionic acid derivatives and flunixin.