Lyophilized Foams of End Block Containing Absorbable Polymers

Patent metadata

Field	Value
Publication number	US-2016355661-A1
Application number	US-201514728226-A
Country	US
Kind code	A1
Filing date	Jun 2, 2015
Priority date	Jun 2, 2015
Publication date	Dec 8, 2016
Grant date	—

Abstract

Novel absorbable foams, lyophilizing solutions, and lyophilizing and annealing processes are disclosed. The foams are made from copolymers of glycolide and epsilon-caprolactone. The foams are useful in or as implantable medical devices.

First claim

We claim:

1 . An absorbable polymer foam, comprising:
a semicrystalline absorbable segmented copolymer having a random segment of repeating units of polymerized glycolide and polymerized epsilon-caprolactone and at least one segment that comprises predominantly polymerized glycolide, wherein the mole ratio of polymerized glycolide to polymerized epsilon-caprolactone of the entire segmented copolymer is between about 55:45 to about 65:35, and having a mole ratio of polymerized glycolide to polymerized epsilon-caprolactone in the random segment between about 45:55 to about 60:40.

2 . The absorbable foam of claim 1 wherein the copolymer has an inherent viscosity between about 0.5 dL/g and about 2.5 dl/g, as measured in a 0.1 g/dl solution of HFIP at 25° C.

3 . The foam of claim 1 in which the solids content is between about 3 weight percent to about 20 weight percent.

4 . The foam of claim 3 having a solid content between 5 weight percent and 15 weight percent.

5 . The foam of claim 1 having a thickness between about 0.5 mm to about 13 mm.

6 . The foam of claim 5 having a thickness between about 1 mm and about 5 mm.

7 . The foam of claim 1 having a compressive pressure at 2 mm height greater than 0.5 gf/mm 2 after 28 days of incubation in a buffer of pH 7.27 at 37° C. under continuous compression.

8 . The foam of claim 7 prepared from 10 weight percent lyophilization solution.

9 . The foam of claim 1 prepared having a degradation coefficient less than −0.095 gf/(mm 2 ·day) when incubated in a buffer of pH 7.27 at 37° C. under continuous compression.

10 . The foam of claim 9 prepared from 10 weight percent lyophilization solution.

11 . The foam of claim 1 having mechanical integrity at least 30 days post implantation.

12 . The foam of claim 1 having mechanical integrity at least 60 days post-implantation.

13 . The foam of claim 1 having a crystallinity level greater than about 10 percent.

14 . The foam of claim 1 having a crystallinity level greater than about 20 percent.

15 . A method of making an absorbable foam by a lyophilization process, comprising the steps of:
a) providing an absorbable polymer comprising a semicrystalline, absorbable, segmented copolymer having repeating units of polymerized glycolide and polymerized epsilon-caprolactone, wherein the mole ratio of polymerized glycolide to polymerized epsilon-caprolactone is about 55:45 to about 65:35, and having a mole ratio of polymerized glycolide to polymerized epsilon-caprolactone in the random segment between about 45:55 to about 60:40; b) dissolving a sufficient quantity of the copolymer in a suitable solvent to form a lyophilizing solution; c) pouring at least a part of the solution at a sufficiently effective temperature to prevent premature gel formation into a suitable mold; d) freezing the solution at a fast enough rate to prevent premature gel formation in order to facilitate solvent removal in a subsequent lyophilization process; and, e) subjecting the frozen solution in the mold to a lyophilizing process, wherein the pressure is lowered and heat is applied to sublimate the solvent and form an absorbable foam.

16 . The method of claim 15 , wherein the copolymer has an inherent viscosity between about 0.5 dL/g and about 2.5 dl/g, as measured in a 0.1 g/dl solution of HFIP at 25° C.

17 . The method of claim 15 , wherein the solvent is selected from the group consisting of 1,4-dioxane, a mixture of at least 90 weight percent 1,4-dioxane and no more than 10 weight percent water, and a mixture of at least 90 weight percent 1,4-dioxane and no more than 10 weight percent of an organic alcohol having a molecular weight of less than 1,500.

18 . The method of claim 15 wherein the solid content of the lyophilization solution is between about 3 and about 20 weight percent.

19 . The method of claim 15 wherein the solid content of the lyophilization solution is between about 5 and about 15 weight percent.

20 . The method of claim 15 wherein the lyophilization solution is poured at a temperature above 50° C. into a suitable mold.

21 . The method of claim 15 , wherein the rate of freezing is equal to or faster than −5° C. per minute.

22 . The method of claim 15 wherein the rate of freezing is equal to or faster than −10° C. per minute.

23 . A lyophilizing solution, comprising:
a solvent selected from the group consisting of 1,4-dioxane, a mixture of at least 90 weight percent 1,4-dioxane and no more than 10 weight percent water, and a mixture of at least 90 weight percent 1,4-dioxane and no more than 10 weight percent of an organic alcohol having a molecular weight of less than 1,500 Daltons; and, about 3 wt. % to about 20 wt. % of a semicrystalline, absorbable, segmented copolymer, having repeating units of polymerized glycolide and polymerized epsilon-caprolactone, wherein the mole ratio of polymerized glycolide to polymerized epsilon-caprolactone is between about 55:45 to about 65:35, and having a mole ratio of polymerized glycolide to polymerized epsilon-caprolactone in the random segment between about 45:55 to about 60:40.

24 . The solution of claim 23 , wherein the copolymer has an inherent viscosity between about 0.5 dL/g and about 2.5 dl/g, as measured in a 0.1 g/dl solution of HFIP at 25° C.

25 . The solution of claim 23 wherein the solid content of the lyophilization solution is between about 3 and about 20 weight percent.

26 . The solution of claim 23 wherein the solid content of the lyophilization solution is between about 5 and about 15 weight percent.

27 . The solution of claim 23 wherein the solution is maintained at a temperature to prevent premature gel formation.

28 . The solution of claim 23 wherein the solution is maintained at a temperature above 50° C.

29 . A method of annealing the foam of claim 1 , wherein the foam is heated to a temperature of about 60° C. to about 110° C. and maintained at the temperature for about 1 hour to about 12 hours.

30 . The method of claim 29 , wherein the foam is heated to a temperature of about 70° C. to about 100° C.

31 . The method of claim 30 , wherein the foam is heated to a temperature of about 85° C. to about 95° C.

32 . The method of claim 29 wherein the foam is heated for about 4 to about 8 hours.

Assignees

• Ethicon Inc

Inventors

• Donners Jackie
• Wisnudel Marc
• Timmer Mark

Classifications

• A61L27/18

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds · CPC title

• A61L31/146

  Porous materials, e.g. foams or sponges · CPC title

• C08J2205/05

  Open cells, i.e. more than 50% of the pores are open · CPC title

• A61L27/56

  Porous materials, {e.g. foams or sponges} · CPC title

• C08G63/08

  Lactones or lactides · CPC title