Treatment method and product for uterine fibroids using purified collagenase
View Patent ↗The invention relates to compositions and methods for treating uterine fibroids, wherein a uterine fibroid treatment agent comprising collagenase in an amount effective to cause shrinkage of uterine fibroids is injected or inserted into the uterine fibroid.
1. A method for the treatment of uterine fibroids in a patient comprising:
injecting or inserting into the uterine fibroid a composition comprising: (a) a thermally responsive polymer having a lower critical solution temperature (LCST) that is less than or equal to the body temperature of said patient; and (b) collagenase,
wherein said composition is formulated such that the thermally responsive polymer entraps and maintains the stability of the collagenase and is non-toxic and biodegradable,
wherein the collagenase is from Clostridium histolyticum , and
wherein said composition is injected at a temperature that is less than said lower critical solution temperature (LCST) to provide about 0.06 to about 1 mg collagenase per 1 cm 3 uterine fibroid tissue.
2. The method of claim 1 , wherein the composition provides sustained release of an amount of said collagenase sufficient to treat said uterine fibroids.
3. The method of claim 1 , wherein about 0.1 mg to about 0.8 mg collagenase is administered per cm 3 of uterine fibroid to be treated.
4. The method of claim 3 , wherein about 0.2 mg to about 0.6 mg collagenase is administered per cm 3 of uterine fibroid to be treated.
5. The method of claim 1 , wherein 100 μL of said composition is injected or inserted into 1 cm 3 uterine fibroid tissue.
6. A composition for treating uterine fibroids in a patient comprising: (a) a thermally responsive polymer having a lower critical solution temperature (LCST) that is less than or equal to the body temperature of said patient; and (b) collagenase,
wherein said composition is formulated such that the thermally responsive polymer entraps and maintains the stability of the collagenase and is non-toxic and biodegradable,
wherein the collagenase is from Clostridium histolyticum , and
wherein said composition is formulated to provide about 0.06 to about 1 mg collagenase per dose administered to 1 cm 3 of uterine fibroid tissue.
7. The composition of claim 6 , wherein said polymer is a triblock polymer or a copolymer based on N-isopropylacrylamide (NIPAAm).
8. The composition of claim 7 , wherein said triblock polymers comprise poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG).
9. The composition of claim 8 , wherein said triblock polymers comprise a copolymer formed from PLGA and polyethylene glycol (PEG).
10. The composition of claim 9 , wherein the PLGA and PEG copolymers are formed in repetitions of PLGA-PEG-PLGA or PEG-PLGA-PEG.
11. The composition of claim 7 , wherein the NIPAAm based polymer is a copolymer based on N-isopropylacrylamide (NIPAAm) and one or more of polylactide-hydroxyethyl methacrylate (HEMAPLA), acrylic acid (AAc), and hyperbranched polyglycerol (HPG).
12. The composition of claim 11 , comprising copolymers of poly-NIPAAm and hyperbranched polyglycerols (HPG).
13. The composition of claim 7 , having a lower critical solution temperature (LCST) of 10-37° C.
14. The composition of claim 6 , wherein said composition is injectable, insertable or applied topically.
15. The composition of claim 6 , which can be administered through a syringe fitted with a 10 gauge or smaller needle without pre-gelation in the needle on injection.
16. The composition of claim 6 , wherein the composition exists as a liquid at temperatures below body temperature and as a gel at body temperature.
17. The composition of claim 6 , wherein the collagenase is a mixture of collagenase I and collagenase II.
18. The composition of claim 6 , wherein the polymer does not negatively affect enzymatic activity of the collagenase.
19. The composition of claim 6 , wherein said composition is formulated to provide about 0.1 to about 0.8 mg collagenase per dose administered to 1 cm 3 of uterine fibroid tissue.
20. The composition of claim 19 , wherein said composition is formulated to provide about 0.2 to about 0.6 mg collagenase per dose administered to 1 cm 3 of uterine fibroid tissue.
21. A composition for treating uterine fibroids in a patient comprising: (a) a thermally responsive polymer having a lower critical solution temperature (LCST) that is less than or equal to the body temperature of said patient; and (b) collagenase,
wherein said composition comprises 0.25-2.0 mg/ml collagenase from Clostridium histolyticum.
22. The composition of claim 21 , comprising 0.25 mg/mL collagenase from Clostridium histolyticum.
23. The composition of claim 21 , comprising 0.5 mg/mL collagenase from Clostridium histolyticum.
24. The composition of claim 21 , comprising 1.0 mg/mL collagenase from Clostridium histolyticum.
25. The composition of claim 21 , comprising 2.0 mg/mL collagenase from Clostridium histolyticum.
26. A method for the treatment of uterine fibroids in a patient comprising:
injecting or inserting into the uterine fibroid a composition comprising: (a) a thermally responsive polymer having a lower critical solution temperature (LCST) that is less than or equal to the body temperature of said patient; and (b) collagenase,
wherein said composition is formulated such that the thermally responsive polymer entraps and maintains the stability of the collagenase and is non-toxic and biodegradable,
wherein the composition comprises 0.25-2.0 mg/mL collagenase from Clostridium histolyticum , and
wherein said composition is injected at a temperature that is less than said lower critical solution temperature (LCST).
27. The method of claim 26 , wherein 100 μL of said composition is injected or inserted into 1 cm 3 uterine fibroid tissue.
28. The method of claim 26 , wherein said composition comprises 0.25 mg/mL collagenase from Clostridium histolyticum.
29. The method of claim 26 , wherein said composition comprises 0.5 mg/mL collagenase from Clostridium histolyticum.
30. The method of claim 26 , wherein said composition comprises 1.0 mg/mL collagenase from Clostridium histolyticum.
31. The method of claim 26 , wherein said composition comprises 2.0 mg/mL collagenase from Clostridium histolyticum.