Process for manufacturing biomedical foams

• US 6,355,699 B1
• Filed: 06/30/1999
• Issued: 03/12/2002
• Est. Priority Date: 06/30/1999
• Status: Expired due to Term

• Current Assignee: Endo-Surgery, Inc.
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Vyakarnam, Murty N., Roller, Mark B., Scopelianos, Angelo George, Gorky, David V.
• Primary Examiner(s): Acquah, Samuel A.
• Application Number:
  US09/345,095
• Time in Patent Office: 986 Days
• Field of Search: 525/437, 525/444, 524/81, 524/9, 524/21, 524/56, 524/58, 524/401, 524/433, 524/425, 424/443, 424/486, 521/61, 521/62, 521/64, 521/82, 521/84.1, 521/50, 521/102, 521/134, 521/138, 528/488, 528/491
• US Class Current: 521/61
• CPC Class Codes: A61L 15/26 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof A61L15/225 takes precedence
• CPC Class Codes: A61L 15/425 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: C08J 2367/02 Polyesters derived from dicarboxylic acids and dihydroxy compounds; C08J2367/06 takes precedence
• CPC Class Codes: C08J 9/26 by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out
• CPC Class Codes: C08J 9/28 by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The present invention provides an improved lyophilization process for forming biocompatible foam structures. The process allows the foam structures to be tailored for specific end uses. The foams formed by this process are well suited to be used in medical applications such as tissue engineering. The foam structures may also contain pharmaceutically active substances

Claims

1. A process for making biomedical absorbable foams comprising solidifying a solution of a solvent and a bioabsorbable polymer to form a solid, then with the solid at a temperature above the apparent Tg of the solid, but below the freezing temperature of the solid subliming the solvent out of the solid to provide a biocompatible porous foam.

2. The process of claim 1 wherein the bioabsorable polymer is an aliphatic polyester.

3. The process of claim 1 wherein the solvent is a liquid at room temperature.

4. The process of claim 2 wherein the aliphatic polyester is selected from the group consisting of homopolymers and copolymers of lactide, lactic acid, glycolide, glycolic acid), ε

-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, δ

-valerolactone, β

butyrolactone, γ

-butyrolactone, ε

-decalactone, hydroxybutyrate, hydroxyvalerate, 1,4-dioxepan-2-one, 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one and polymer blends thereof.

5. The process of claim 2 wherein the aliphatic polyester is an elastomer.

6. The process of claim 5 wherein the elastomer is selected from the group consisting of copolymers of ε

-caprolactone and glycolide;

copolymers of ε

-caprolactone and lactide, copolymers of p-dioxanone (1,4-dioxan-2-one) and lactide, copolymers of ε

-caprolactone and p-dioxanone, copolymers of p-dioxanone and trimethylene carbonate, copolymers of trimethylene carbonate and glycolide, copolymer of trimethylene carbonate and lactide and blends thereof.

7. The process of claim 2 wherein additional present in the mixture is a second aliphatic polyester.

8. The process of claim 7 wherein the second aliphatic polyester is also soluble in the solvent.

9. The process of claim 1 wherein also present in the mixture are solids.

10. The process of claim 9 wherein the solids particles are selected from the group consisting of demineralized bone particles, calcium phosphate particles, calcium carbonate particles, nonsoluble aliphatic polyester particles and combinations thereof.

11. The process of claim 9 wherein also present is the mixture is a leachable solid.

12. The process of claim 1 wherein the leachable solid is selected from the group consisting of sodium chloride, potassium chloride, calcium chloride, sodium tartrate, sodium citrate, dextrose maltose, lactose and sucrose, alginate, gelatin and agarose.

13. The process of claim 1 wherein the mixture is placed into a mold.

14. The process of claim 13 wherein the mold also contains an insert.

15. The process of claim 1 wherein the solid is shaped prior to the solvent being sublimed from the solid.

16. The process of claim 1 wherein the mixture is solidified around a cold finger.

17. The process of claim 2 wherein the solvent is removed by subliming in less than 72 hours.

18. The process of claim 2 wherein the solvent is removed by subliming in less than 48 hours.

19. The process of claim 2 wherein the solvent is removed by subliming in less than 10 hours.

20. The process of claim 2 wherein also present in the mixture is a therapeutic agent.

21. The process of claim 20 wherein the therapeutic agent is selected from the group consisting of antiinfectives, hormones, analgesics, anti-inflammatory agents, growth factors and combinations thereof.

36. The process of claim 8 wherein a solution of the first and second aliphatic polyester are cooled at a rate slow enough to allow phase separation upon solidifiction of the first and second aliphatic polyester.

22. A process for making biomedical foams with channels therein comprising solidifying a mixture of a solvent and a bioabsorbable polymer to form a substantially solidified but not completely solidified material, then subliming the solvent out of the material to provide a biocompatible porous foam that has a porous structure with channels.

23. The process of claim 22 wherein the biomedical foams are processed to provide channels with an average diameter of from about 20 to about 200 microns.

24. The process of claim 23 wherein the channels are at least two times the average diameter in length.

25. The process of claim 23 wherein the channels are at least four times the average diameter in length.

26. The process of claim 22 wherein the porous foam structure is processed to have pores having a diameter that on average is from about 10 to about 200 microns.

27. The process of claim 22 wherein the bioabsorbable polymer is an aliphatic polyester.

28. The process of claim 22 wherein the solvent is a liquid at room temperature.

29. The process of claim 22 wherein the aliphatic polyester is selected from the group consisting of homopolymers and copolymers of lactide, lactic acid, glycolide, glycolic acid), ε

-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, δ

-valerolactone, β

butyrolactone, γ

-butyrolactone, ε

-decalactone, hydroxybutyrate, hydroxyvalerate, 1,4-dioxepan-2-one, 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one and polymer blends thereof.

30. The process of claim 22 wherein the aliphatic polyester is an elastomer.

31. A process for making biomedical foams with a gradient of pores therein comprising solidifying a mixture of a solvent and a bioabsorbable polymer to form a substantially solidified but not completely solidified material, then subliming the solvent out of the material to provide a biocompatible porous foam that has a gradient of pore sizes.

32. The process of claim 31 wherein the bioabsorbable polymer is an aliphatic polyester.

33. The process of claim 31 wherein the solvent is a liquid at room temperature.

34. The process of claim 31 wherein the aliphatic polyester is selected from the group consisting of homopolymers and copolymers of lactide, lactic acid, glycolide, glycolic acid), ε

-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, δ

-valerolactone, β

butyrolactone, γ

-butyrolactone, ε

-decalactone, hydroxybutyrate, hydroxyvalerate, 1,4-dioxepan-2-one, 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one and polymer blends thereof.

35. The process of claim 31 wherein the aliphatic polyester is an elastomer.