Absorbable Medical Devices Based on Novel Films and Foams Made From Semi-Crystalline, Segmented Copolymers of Lactide and Epsilon-Caprolactone Exhibiting Long Term Absorption Characteristics

Patent metadata

Field	Value
Publication number	US-2016354510-A1
Application number	US-201514728177-A
Country	US
Kind code	A1
Filing date	Jun 2, 2015
Priority date	Jun 2, 2015
Publication date	Dec 8, 2016
Grant date	—

Abstract

Absorbable medical devices based on novel foams and films made from semi-crystalline, segmented copolymers of lactide and epsilon-caprolactone exhibiting long term absorption characteristics are disclosed. Also disclosed are methods of producing said foams and films, and useful polymer solutions.

First claim

We claim:

1 . An absorbable foam, comprising a semicrystalline absorbable segmented copolymer, said copolymer comprising repeating units of polymerized lactide and polymerized epsilon-caprolactone, wherein the mole ratio of polymerized lactide to polymerized epsilon-caprolactone is between about 60:40 to about 75:25, said copolymer having a first heat Tg, as determined by differential scanning calorimetry at a scan rate of 10° C. per minute, equal to or less than 0° C., and a crystallinity level of about 20 percent to about 50 percent, as measured by wide angle X-ray diffraction.

2 . The foam of claim 1 in which the solids content is between about 3 weight percent to about 30 weight percent.

3 . The foam of claim 2 having a solid content between 5 weight percent and 20 weight percent.

4 . The foam of claim 1 having a thickness between about 20 mils to about 500 mils.

5 . The foam of claim 4 having a thickness between about 40 mils and about 200 mils.

6 . The foam of claim 1 having mechanical integrity at least 40 days post-implantation or having mechanical integrity after at least 40 days of incubation in a buffer of pH 7.27 at 37° C.

7 . The foam of claim 1 having mechanical integrity at least 64 days post-implantation or having mechanical integrity after at least 64 days of incubation in a buffer of pH 7.27 at 37° C.

8 . The foam of claim 1 having a crystallinity level great than about 25 percent.

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

10 . A method of making an absorbable foam by a melt process, comprising the steps of:
A. providing an absorbable polymer comprising a semicrystalline absorbable segmented copolymer, said copolymer comprising repeating units of polymerized lactide and polymerized epsilon-caprolactone, wherein the mole ratio of polymerized lactide to polymerized epsilon-caprolactone is between about 60:40 to about 75:25, said copolymer having a first heat Tg, as determined by differential scanning calorimetry at a scan rate of 10° C. per minute, equal to or less than 0° C., and a crystallinity level of about 20 to about 50 percent, as measured by wide angle X-ray diffraction, said copolymer having a melt temperature; B. heating the copolymer above the melt temperature to form a melt; C. introducing a suitable blowing agent (chemical or physical) into the melt; and D. enabling the gas produced from the blowing agent to expand within the melt to form an absorbable foam.

11 . A method of making an absorbable foam by a melt process, comprising the steps of:
A. providing an absorbable polymer comprising a semicrystalline absorbable segmented copolymer, said copolymer comprising repeating units of polymerized lactide and polymerized epsilon-caprolactone, wherein the mole ratio of polymerized lactide to polymerized epsilon-caprolactone is between about 60:40 to about 75:25, said copolymer having a first heat Tg, as determined by differential scanning calorimetry at a scan rate of 10° C. per minute, equal to or less than 0° C., and a crystallinity level of about 20 to about 50 percent, as measured by wide angle X-ray diffraction, said copolymer having a melt temperature; B. transferring the said absorbable polymer to the hopper of a melt extruder outfitted with a profile die, with a barrel outfitted with a gas injection port, and die heated to a temperature within the range of about 10° C. above the melt temperature of said absorbable polymer to about 270° C. to form a melt; C. extruding said absorbable polymer through said profile die, while injecting into the melt through the gas injection port a gas selected from the group of carbon dioxide, nitrogen, helium, and argon, resulting in a foam; and, D. collecting said foam at a rate to result in a foam thickness between about 0.1 mils and 50 mils.

12 . A method of making an absorbable foam by a melt process, comprising the steps of:
A. providing an absorbable polymer comprising a semicrystalline absorbable segmented copolymer, said copolymer comprising repeating units of polymerized lactide and polymerized epsilon-caprolactone, wherein the mole ratio of polymerized lactide to polymerized epsilon-caprolactone is between about 60:40 to about 75:25, said copolymer having a first heat Tg, as determined by differential scanning calorimetry at a scan rate of 10° C. per minute, equal to or less than 0° C., and a crystallinity level of about 20 to about 50 percent, as measured by wide angle X-ray diffraction, said copolymer having a melt temperature; B. transferring the said absorbable polymer in combination with a solid blowing agent to the hopper of a melt extruder outfitted with a profile die, and die heated to a temperature within the range of about 10° C. above the melt temperature of said absorbable polymer to about 270° C.; C. extruding said absorbable polymer through said profile die, resulting in a foam; and, D. collecting said foam at a rate to result in a foam thickness between about 0.1 mils and 50 mils.

13 . 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, said copolymer comprising repeating units of polymerized lactide and polymerized epsilon-caprolactone, wherein the mole ratio of polymerized lactide to polymerized epsilon-caprolactone is between about 60:40 to about 75:25, said copolymer having a first heat Tg, as determined by differential scanning calorimetry at a scan rate of 10° C. per minute, equal to or less than 0° C., and a crystallinity level of about 20 to about 50 percent, as measured by wide angle X-ray diffraction; 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 into a suitable mold; and, D. subjecting the solution in the mold to a lyophilizing process to form an absorbable foam.

14 . The method of claim 13 wherein the solvent is selected from the group consisting of 1,4-dioxane, trioxane, 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 1500 Daltons.

15 . The method of claim 13 wherein the dissolved absorbable polymer is between about 3 to about 30 percent by weight of the solution.

16 . The method of claim 13 wherein the resulting foam has a thickness between about 20 to about 500 mils.

17 . A lyophilizing solution, comprising:
A. a solvent selected from the group consisting of 1,4-dioxane, trioxane, 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 1500 Daltons; and, B. about 3 wt. % to about 30 wt. % of a polymer comprising a semicrystalline absorbable segmented copolymer, the copolymer comprising repeating units of polymerized lactide and polymerized epsilon-caprolactone, wherein the mole ratio of polymerized lactide to polymerized epsilon-caprolactone is between about 60:40 to about 75:25, said copolymer having a first heat Tg, as determined by differential scanning calorimetry at a scan rate of 10° C. per minute, equal to or less than 0° C., and a crystallinity level of about 20 to about 50 percent, as measured

Assignees

• Ethicon Inc

Inventors

• Andjelic Sasa
• Jamiolkowski Dennis D
• Donners Jackie
• Timmer Mark

Classifications

• C08L67/04

  Polyesters derived from hydroxycarboxylic acids, e.g. lactones (C08L67/06 takes precedence) · CPC title

• C08G2101/00

  Manufacture of cellular products · CPC title

• A61L31/148

  Materials at least partially resorbable by the body · CPC title

• A61L31/06

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds {(A61L31/041 takes precedence)} · CPC title

• C08J9/26 Primary

  by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out · CPC title