Claims for Patent: 10,272,140

Summary for Patent: 10,272,140

Title:	Thermosensitive hydrogel collagenase formulations
Abstract:	It is an object of the present disclosure to provide a formulation for injectable collagenase which will have extended residence time for the drug at the therapeutic targeted area for the indication being treated. It is a further object of the disclosure to provide a slow release formulation for collagenase which is compatible with the active ingredient and does not adversely affect its activity. Still a further object of the disclosure is to provide an injectable formulation for collagenase which can be effectively administered to a patient with a small size needle without exhibiting pregelation, which would interfere with the ability to deliver the required dose for treatment.
Inventor(s):	Yu; Bo (Fresh Meadows, NY), Wegman; Thomas L. (North Merrick, NY)
Assignee:	BIOSPECIFICS TECHNOLOGIES CORP. (Lynbrook, NY)
Application Number:	15/112,007
Patent Claims:	1. A sterile injectable formulation comprising: (1) a thermosensitive triblock polymer hydrogel; (2) an effective amount of a 1:1 mixture of Aux I and Aux II Clostridium histolyticum collagenase; and (3) an amount of tris (hydroxymethyl) amino methane to provide a pH of about 8.5, said formulation upon injection into a therapeutic target site in a subject having need of collagenase treatment provides to said site a gel capable of slow release of free, active collagenase mixture for no longer than about two days after injection, wherein said triblock polymer hydrogel is a poly (DL-lactic acid-co-glycolic acid) and poly (ethylene glycol) polymer of the structure PLGA-PEG-PLGA; and wherein said thermosensitive hydrogel entraps at least about 80% of said collagenase. 2. The sterile formulation of claim 1 which can be administered through a syringe fitted with a 28G1/2 needle without pregelation in the needle on injection. 3. A method for treating a subject suffering from a disease involving a collagen lesion which comprises injecting into the lesion the formulation of claim 1. 4. The method of claim 3 wherein said injection is made with a syringe fitted with a 28G1/2 needle without pregelation in said needle on injection. 5. The method of claim 3 wherein said disease is selected from Dupuytren's contracture, Peyronie's disease, frozen shoulder, human lipoma, canine lipoma, cellulite and uterine fibroids. 6. A kit for providing at least one therapeutic dose of the sterile injectable formulation of claim 1 through a syringe fitted with a 28G1/2 needle without pregelation in the needle on injection said kit comprising in a unit package at least one container containing a sterile thermosensitive hydrogel fluid of a triblock polymer having the structure PLGA-PEG-PLGA where PLGA is poly (DL-lactic acid-co- glycolic acid) and PEG is poly (ethylene glycol) and an amount of tris (hydroxymethyl) amino methane to provide a pH of about 8.5 in an amount sufficient for at least one therapeutic dose; at least one second container containing an effective amount of a 1:1 mixture of Aux I and Aux II Clostridium histolyticum collagenases in lyophilized, powder form and a package insert, wherein the formulation provides a gel capable of slow release of free, active collagenase mixture for no longer than about two days after injection. 7. The kit of claim 6 wherein the kit is maintained in a frozen form during storage. 8. A process for the preparation of the sterile injectable formulation of claim 1, said process comprising: (1) providing a thermosensitive hydrogel solution by mixing an amount of a triblock polymer having the structure PLGA-PEG-PLGA where PLGA is poly (DL-lactic acid-co- glycolic acid) and PEG is poly (ethylene glycol) with water and adding a sufficient amount of tris (hydroxymethyl) amino methane to said solution to provide a pH of about 8.5 (2) sterilizing said resulting solution from step (1); and (3) mixing said sterilized solution from step (2) with a therapeutically effective dose of a 1:1 mixture of Aux I and Aux II Clostridium histolyticum collagenase, thereby providing said sterile injectable formulation of claim 1. 9. The process of claim 8 wherein said sterilizing step is accomplished by filtering the solution from step (1) through a 0.22 .mu.m filter. 10. The process of claim 8 wherein said tris (hydroxymethyl) amino methane solution is added to the hydrogel solution just prior to injection and is sterile.

Details for Patent 10,272,140

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2034-01-15