Claims for Patent: 6,296,847

Summary for Patent: 6,296,847

Title:	Composition for treating benign prostatic hypertrophy
Abstract:	The invention provides a composition and method for treating benign prostatic hypertrophy in mammals so as to cause the dissolution and regression of hypertrophied prostatic tissue and thereby provide relief from the obstructive symptoms associated with the disease. The present composition preferably comprises a sterile pyrogen-free solution of the hydrolytic enzymes collagenase and hyaluronidase, a nonionic surfactant, and an antibiotic; all provided, in a pharmaceutically acceptable, buffered, isotonic, aqueous carrier. The present method preferably comprises the direct intraprostatic injection of a safe and therapeutically effective dose of the composition via the transurethral route of administration.
Inventor(s):	Gokcen; Muharrem (Minneapolis, MN), Guy; Terry J. (Chaska, MN)
Assignee:	Immunolytics, Inc. (Minneapolis, MN)
Application Number:	08/154,158
Patent Claims:	1. A composition for treating prostatic hypertrophy in living mammals, comprising: a therapeutically effective concentration of collagenase and a therapeutically effective concentration of hyaluronidase, the composition being suitable for administration by direct intraprostatic injection; the concentration of the collagenase and hyaluronidase being effective to cause the dissolution and regression of obstructive, hypertrophied, living prostatic tissue; the concentration of the hyaloronidase being about 1,600 to about 160,000 U/ml. 2. The composition of claim 1, wherein said collagenase is present at a concentration of about 250 to 250,000 U/ml. 3. The composition of claim 2 wherein said collagenase is present at a concentration of about 2,500 to 25,000 U/ml and hyaluronidase at a concentration of about 1,600 to 16,000 U/ml. 4. The composition of claim 1 further including an effective amount of a nonionic surfactant. 5. The composition of claim 4 wherein said surfactant is selected from the group consisting of ethylene oxide esters of C.sub.10 -C.sub.20 fatty acids, and ethylene oxide esters of C.sub.8 -C.sub.22 alkyl alcohols. 6. The composition of claim 5 wherein said nonionic surfactant is either octylphenyl polyoxyethylene oxide or octylphenoxy polyethoxyethanol. 7. The composition of claim 4 wherein said nonionic surfactant is present at a concentration of about 0.1% to 10% by volume. 8. The composition of claim 7 wherein said nonionic surfactant is present at a concentration of about 0.5% to 5% by volume. 9. The composition of claim 1 further including an antibiotic selected from the group consisting of aminoglycosides, sulfonamides, penicillins, cephalosporins, basic macrolides, tetracyclines, polymyxins, fluoroquinolones, lincomycin, clindamycin, chloramphenicol, nitrofurantoin, and nalidixic acid. 10. The composition of claim 9 wherein said antibiotic is gentamicin sulfate. 11. The composition of claim 9 wherein said antibiotic is present at a concentration of about 1.5 to 150 .mu.g/ml. 12. The composition of claim 11 wherein said composition comprises a sterile pyrogen-free solution of about 2,500 to 25,000 U/ml collagenase, 1,600 to 16,000 U/ml hyaluronidase, 0.5% to 5% by volume of a nonionic surfactant, and 1.5 to 150 .mu.g/ml of an antibiotic; said composition provided in a buffered, isotonic, aqueous carrier comprising about 0.05 M to 0.1M sodium citrate, about 0.15 M to 0.2 M sodium chloride, about 0.02 M to 0.05 M calcium chloride, having a pH of about 6.7 to 7.0. 13. The composition of claim 11 further including a pharmaceutically acceptable aqueous carrier solution having a physiologic pH. 14. The composition of claim 13 wherein said aqueous carrier comprises 0.02 M to 0.1 M sodium citrate, 0.1 M to 0.2 M sodium chloride, 0.01 M to 0.05 M calcium chloride, and has a pH of about 6.5 to 7.5. 15. The composition of claim 14 wherein said aqueous carrier comprises 0.05 M to 0.1 M sodium citrate, 0.15 M to 0.2 M sodium chloride, 0.02 M to 0.05 M calcium chloride, and has a pH of about 6.7 to 7.0. 16. The composition of claim 13 wherein said aqueous carrier is a sterile, pyrogen-free, buffered, isotonic, aqueous carrier. 17. The composition of claim 16 wherein said aqueous carrier is selected from the group consisting of citrate buffered saline, tris buffered saline, and Ringers saline. 18. The composition of claim 17 wherein said aqueous carrier comprises citrate buffered saline containing calcium ions. 19. The composition of claim 1 wherein the concentration of the hyaluronidase is about 1,600 to 160,000 U/ml. 20. The composition of claim 1 wherein said composition is provided in a pharmaceutically acceptable aqueous carrier solution having a physiologic pH. 21. The composition of claim 11 wherein said antibiotic is present at a concentration of about 10 to 25 .mu.g/ml. 22. The composition of claim 9 wherein said antibiotic comprises trimethoprim/sulfamethoxazle. 23. The composition of claim 22 wherein said antibiotic is present at a concentration of about 1 to 10 .mu.g/ml trimethoprim and 30 to 105 .mu.g/ml sulfamethoxasole. 24. The composition of claim 23 wherein said antibiotic is present at a concentration of about 5 to 10 .mu.g/ml trimethoprim and 50 to 105 .mu.g/ml sulfamethoxazole. 25. The composition of claim 20 wherein said aqueous carrier is a sterile, pyrogen-free, buffered, isotonic, aqueous carrier. 26. The composition of claim 25 wherein said aqueous carrier is selected from the group consisting of citrate buffered saline, tris buffered saline, and Ringers saline. 27. The composition of claim 26 wherein said aqueous carrier comprises citrate buffered saline containing calcium ions. 28. A kit for treating prostatic hypertrophy in living mammals, comprising: sterile sealed vials containing at least one separate injectable unit-dosage of a composition comprising a therapeutically effective concentration of collagenase, hyaluronidase, and a nonionic surfactant; the concentration of the collagenase and hyaluronidase being effective to cause the dissolution and regression of obstructive, hypertrophied, living prostatic tissue; the concentration of the hyaluronidase being about 1,600 to about 160,000 U/ml; all provided in a pharmaceutically acceptable aqueous carrier suitable for injection into living mammals. 29. The kit of claim 28 wherein said at least one separate injectable unit-dosage comprises collagenase at a concentration of about 250 to 250,000 U/ml. 30. The kit of claim 29 wherein said at least one separate injectable unit-dosage is about 1 to 20 ml. 31. The kit of claim 28 wherein said sterile sealed vials contain a lyophilisate of said composition; whereupon reconstitution with sterile pyrogen-free water provides at least one separate injectable unit-dosage of about 1 to 20 ml of said composition which may be withdrawn as a pharmaceutically acceptable solution for intraprostatic injection into living mammals.

Details for Patent 6,296,847

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	05/05/2004		2018-10-02
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	12/02/2004		2018-10-02
Amphastar Pharmaceuticals, Inc.	AMPHADASE	hyaluronidase	Injection	021665	10/26/2004		2018-10-02
Akorn, Inc.	HYDASE	hyaluronidase	Injection	021716	10/25/2005		2018-10-02