Claims for Patent: 5,658,956

Summary for Patent: 5,658,956

Title:	Bioadhesive-wound healing compositions and methods for preparing and using same
Abstract:	The present invention pertains to therapeutic bioadhesive-wound healing compositions useful for treating wounds and increasing the proliferation and resuscitation rate of mammalian cells. The compositions comprise a bioadhesive agent and a therapeutically effective amount of a wound healing composition. In one embodiment the wound healing composition comprises (a) pyruvate; (b) an antioxidant; and (c) a mixture of saturated and unsaturated fatty acids. The therapeutic bioadhesive-wound healing compositions may further comprise medicaments such as antiviral agents, antikeratolytic agents, anti-inflammatory agents, antifungal agents, antibacterial agents, immunostimulating agents, and the like. The bioadhesive-wound healing compositions may be utilized in a wide variety of pharmaceutical products. This invention also relates to methods for preparing and using the bioadhesive-wound healing compositions and the pharmaceutical products in which the compositions may be used.
Inventor(s):	Martin; Alain (Ringoes, NJ), Leung; Sau-Hung S. (Parsippany, NJ)
Assignee:	Warner-Lambert Company (Morris Plains, NJ)
Application Number:	08/445,824
Patent Claims:	1. A therapeutic bioadhesive-wound healing composition which comprises a therapeutically effective amount of a bioadhesive agent and a wound healing composition, wherein the wound healing composition comprises: (a) pyruvate selected from the group consisting of pyruvic acid, pharmaceutically acceptable salts of pyruvic acid, and mixtures thereof; (b) an antioxidant; and (c) a mixture of saturated and unsaturated fatty acids wherein the fatty acids are those fatty acids required for the resuscitation of injured mammalian cells; wherein components a, b, and c are present in amounts sufficient to synergistically enhance wound healing. 2. The composition according to claim 1, wherein the bioadhesive agent is selected from the group consisting of polyacrylic acids crosslinked with polyhydroxy compounds, carboxymethylcellulose, methylcellulose, guar gum, and polycarbophils. 3. The composition according to claim 2, wherein the bioadhesive agent is a polycarbophil. 4. The composition according to claim 1, wherein the pyruvate is selected from the group consisting of pyruvic acid, lithium pyruvate, sodium pyruvate, potassium pyruvate, magnesium pyruvate, calcium pyruvate, zinc pyruvate, manganese pyruvate, methyl pyruvate, .alpha.-ketoglutaric acid, pharmaceutically acceptable salts of pyruvic acid, prodrugs of pyruvic acid, and mixtures thereof. 5. The composition according to claim 4, wherein the pyruvate is sodium pyruvate. 6. The composition according to claim 1, wherein the antioxidant is selected from the group consisting of all forms of Vitamin A; all forms of carotene; all forms of Vitamin C; all forms of Vitamin E; Vitamin E esters which readily undergo hydrolysis to Vitamin E; prodrugs of Vitamin A, carotene, Vitamin C, and Vitamin E; pharmaceutically acceptable salts of Vitamin A, carotene, Vitamin C, and Vitamin E; and mixtures thereof. 7. The composition according to claim 6, wherein the antioxidant is Vitamin E acetate. 8. The composition according to claim 1, wherein the mixture of saturated and unsaturated fatty acids comprises animal and vegetable fats and waxes. 9. The composition according to claim 8, wherein the mixture of saturated and unsaturated fatty acids is selected from the group consisting of human fat, chicken fat, cow fat, sheep fat, horse fat, pig fat, and whale fat. 10. The composition according to claim 9, wherein the mixture of saturated and unsaturated fatty acids comprises lauric acid, myristic acid, myristoleic acid, pentadecanoic acid, palmitic acid, palmitoleic acid, margaric acid, margaroleic acid, stearic, oleic acid, linoleic acid, linolenic acid, arachidic acid, and gadoleic acid. 11. The composition according to claim 1, wherein the bioadhesive agent is present in the therapeutic wound healing composition in an amount from about 0.01% to about 90%, by weight of the therapeutic wound healing composition. 12. The composition according to claim 1, wherein pyruvate is present in the therapeutic wound healing composition in an amount from about 10% to about 50%, by weight of the therapeutic wound healing composition. 13. The composition according to claim 1, wherein the antioxidant is present in the therapeutic wound healing composition in an amount from about 0.1% to about 40%, by weight of the therapeutic wound healing composition. 14. The composition according to claim 1, wherein the mixture of saturated and unsaturated fatty acids is present in the therapeutic wound healing composition in an amount from about 10% to about 50%, by weight of the therapeutic wound healing composition. 15. A method for treating a wound in a mammal with comprises administering to a mammal in need thereof: a therapeutic bioadhesive-wound healing composition which comprises: (1) a bioadhesive agent; and (2) a therapeutically effective amount of a wound healing composition comprising: (a) pyruvate selected from the group consisting of pyruvic acid, pharmaceutically acceptable salts of pyruvic acid, and mixtures thereof; (b) an antioxidant; and (c) a mixture of saturated and unsaturated fatty acids wherein the fatty acids are those fatty acids required for the resuscitation of injured mammalian cells; wherein components a, b, and c are present in synergistic amounts sufficient to synergistically enhance wound healing. 16. An augmented bioadhesive-wound healing composition which comprises: (A) a therapeutic bioadhesive-wound healing composition which comprises: (1) a therapeutically effective amount of a bioadhesive agent; and (2) a wound healing composition which comprises: (a) pyruvate selected from the group consisting of pyruvic acid, pharmaceutically acceptable salts of pyruvic acid, and mixtures thereof; (b) an antioxidant; and (c) a mixture of saturated and unsaturated fatty acids wherein the fatty acids are those fatty acids required for the repair of cellular membranes and resuscitation of mammalian cells; wherein components a, b, and c are present in amounts sufficient to synergistically enhance wound healing; and, (B) a medicament useful for treating wounds. 17. The augmented bioadhesive-wound healing composition according to claim 16, wherein the medicament useful for treating wounds is selected from the group consisting of immunostimulating agents, antiviral agents, antikeratolytic agents, anti-inflammatory agents, antifungal agents, acne treating agents, sunscreen agents, dermatological agents, antihistamine agents, antibacterial agents, bioadhesive agents, respiratory bursting inhibitors, inhibitors of prostaglandin synthesis, antimicrobial agents, antiseptic agents, anesthetic agents, cell nutrient media, burn relief medications, sun burn medications, insect bite and sting medications, wound cleansers, wound dressings, scar reducing agents, and mixtures thereof. 18. The augmented bioadhesive-wound healing composition according to claim 16, wherein the medicament useful for treating wounds is selected from the group consisting of immunostimulating agents, antiviral agents, antikeratolytic agents, anti-inflammatory agents, antifungal agents, acne treating agents, sunscreen agents, dermatological agents, antihistamine agents, antibacterial agents, bioadhesive agents. 19. The augmented bioadhesive-wound healing composition according to claim 17, wherein the medicament useful for treating wounds is an immunostimulating agent selected from the group consisting of betafectin.TM. and Freund's complete adjuvant. 20. The augmented bioadhesive-wound healing composition according to claim 16, wherein the medicament useful for treating wounds is a cytotoxic agent selected from the group consisting of epithelial cell cohesiveness reducers, dermatological abradants, anti-inflammatories, lipid regulating agents, centrally acting anticholinesterases, chemotherapeutic drugs, and gastric irritants. 21. The augmented bioadhesive-wound healing composition according to claim 17, wherein the medicament useful for treating wounds is an antiviral agent selected from the group consisting of acyclovir, foscarnet sodium, ribavirin, vidarabine, ganeiclovir sodium, zidovudine, phenol, amantadine hydrochloride, and interferon alfa-n3. 22. The augmented bioadhesive-wound healing composition according to claim 17, wherein the medicament useful for treating wounds is an antikeratolytic agent selected from the group consisting of salicylic acid, lactic acid, and urea. 23. The augmented bioadhesive-wound healing composition according to claim 17, wherein the medicament useful for treating wounds is an anti-inflammatory agent selected from the group consisting of ibuprofen, naproxen, sulindac, diflunisal, piroxicam, indomethacin, etodolac, meclofenamate sodium, fenoproben calcium, ketoprofen, mefenamic acid, nabumetone, ketorolac tromethamine, diclofenac, evening primrose oil, acetylsalicylic acid, mesalamine, salsalate, diflunisal, salicylsalicylic acid, choline magnesium trisalicylate, flunisolide, triamcinoline, triamcinoline acetonide, beclomethasone diproprionate, betamethasone diproprionate, hydrocortisone, cortisone, dexamethasone, prednisone, methyl prednisolone, and prednisolone. 24. The augmented bioadhesive-wound healing composition according to claim 17, wherein the medicament useful for treating wounds is an antifungal agent selected from the group consisting of lactic acid, sorbic acid, miconazole, clotrimazole, tioconazole, terconazole, povidone-iodine, and butoconazole. 25. The augmented bioadhesive-wound healing composition according to claim 17, wherein the medicament useful for treating wounds is tretinoin. 26. The augmented bioadhesive-wound healing composition according to claim 17, wherein the medicament useful for treating wounds is a sunscreen agent selected from the group consisting of ethylhexyl p-methoxycinnamate, octyl methoxycinnamate, octyl dimethyl p-aminobenzoic acid, 2-ethylhexyl salicylate, octyl salicylate, menthyl anthranilate, octocrylene, padimate o, titanium dioxide, urea, and oxybenzone. 27. The augmented bioadhesive-wound healing composition according to claim 17, wherein the medicament useful for treating wounds is a buffering agent to maintain the pH of dermatitis in a range from about 5 to about 8 together with an anti-inflammatory agent. 28. The augmented bioadhesive-wound healing composition according to claim 17, wherein the medicament useful for treating wounds is a topical antihistamine agent selected from the group consisting of diphenhydramine hydrochloride and pramoxine hydrochloride. 29. The augmented bioadhesive-wound healing composition according to claim 17, wherein the medicament useful for treating wounds is an antibacterial agent selected from the group consisting of bismuth compounds, such as bismuth aluminate, bismuth subcitrate, bismuth subgalate, bismuth subsalicylate; the sulfonamides; the nitrofurans, such as nitrofurazone and nitrofurantoin; furazolidone, metronidazole, tinidazole, nimorazole, benzoic acid, the aminoglycosides; such as gentamicin, neomycin, kanamycin, and streptomycin; the macrolides, such as erythromycin, clindamycin, and rifamycin; the penicillins, such as penicillin G, penicillin V, Ampicillin and amoxicillin; the polypeptides, such as bacitracin and polymyxin; the tetracyclines, such as tetracycline, chlorotetracycline, oxytetracycline, and doxycycline; the cephalosporins, such as cephalexin and cephalothin; and chloramphenicol, and clidamycin. 30. A method for treating a wound in a mammal with an augmented bioadhesive-wound healing composition which comprises administering to a mammal in need thereof: (A) a therapeutic augmented bioadhesive-wound healing composition which comprises: (1) a therapeutically effective amount of a bioadhesive agent; (2) a wound healing composition which comprises: (a) pyruvate selected from the group consisting of pyruvic acid, pharmaceutically acceptable salts of pyruvic acid, and mixtures thereof; (b) an antioxidant; and (c) a mixture of saturated and unsaturated fatty acids wherein the fatty acids are those fatty acids required for the repair of cellular membranes and resuscitation of mammalian cells; wherein components a, b, and c are present in amounts sufficient to synergistically enhance wound healing; and, (3) a medicament useful for treating wounds. 31. The method according to claim 29, wherein the medicament useful for treating wounds is selected from the group consisting of immunostimulating agents, antiviral agents, antikeratolytic agents, anti-inflammatory agents, antifungal agents, acne treating agents, sunscreen agents, dermatological agents, antihistamine agents, antibacterial agents, bioadhesive agents, respiratory bursting inhibitors, inhibitors of prostaglandin synthesis, antimicrobial agents, antiseptic agents, anesthetic agents, cell nutrient media, burn relief medications, sun burn medications, insect bite and sting medications, wound cleansers, wound dressings, scar reducing agents, and mixtures thereof. 32. A bioadhesive-wound healing pharmaceutical composition which comprises: (A) a therapeutic bioadhesive-wound healing composition which comprises: (1) a therapeutically effective amount of a bioadhesive agent; and (2) a wound healing composition which comprises: (a) pyruvate selected from the group consisting of pyruvic acid, pharmaceutically acceptable salts of pyruvic acid, and mixtures thereof; (b) an antioxidant; and (c) a mixture of saturated and unsaturated fatty acids wherein the fatty acids are those fatty acids required for the repair of cellular membranes and resuscitation of mammalian cells; wherein components a, b, and c are present in amounts sufficient to synergistically enhance wound healing; and (B) a pharmaceutically acceptable carrier selected from the group consisting of pharmaceutical appliances, bioadhesives, and occlusive vehicles.

Details for Patent 5,658,956

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Hemispherx Biopharma, Inc.	ALFERON N INJECTION	interferon alfa-n3 (human leukocyte derived)	Injection	103158	10/10/1989		2014-08-19
Hoffmann-la Roche Inc.	PEGASYS COPEGUS COMBINATION PACK	peginterferon alfa-2a and ribavirin		125083	06/04/2004		2014-08-19
Schering Corporation A Subsidiary Of Merck & Co., Inc.	PEGINTRON/ REBETOL COMBO PACK	peginterferon alfa-2b and ribavirin		125196	06/13/2008		2014-08-19