Method for making a porous polymeric material

• US 20050075408A1
• Filed: 09/23/2004
• Published: 04/07/2005
• Est. Priority Date: 05/13/1994
• Status: Active Grant

• Current Assignee: DSM IP Assets BV (DSM-Firmenich AG)
• Original Assignee: Kensey Nash Corporation (DSM-Firmenich AG)
• Inventors: Goldman, Scott M., Ringeisen, Timothy A.
• Granted Patent: US 8,697,108 B2
• Time in Patent Office: Days
• US Class Current: 521/64
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: B29C 41/12 Spreading-out the material on a substrate , e.g. on the surface of a liquid
• CPC Class Codes: B29C 41/14 Dipping a core B29C41/10 takes precedence
• CPC Class Codes: B29C 45/0001 characterised by the choice of material
• CPC Class Codes: C08J 2201/054 Precipitating the polymer by adding a non-solvent or a different solvent
• CPC Class Codes: C08J 9/0014 Use of organic additives
• CPC Class Codes: C08J 9/0023 containing oxygen
• CPC Class Codes: C08J 9/0028 containing nitrogen
• CPC Class Codes: C08J 9/0033 containing sulfur
• CPC Class Codes: C08J 9/28 by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum

Abstract

Porous polymers having a plurality of openings or chambers that are highly convoluted, with each chamber being defined by multiple, thin, flat partitions are produced by a new gel enhanced phase separation technique. In a preferred embodiment, a second liquid is added to a polymer solution, the second liquid causing the solution to increase in viscosity. With sufficient polymer and second liquid present, the increase in viscosity can be up to that of a gel. The gel can then be shaped as needed. Subsequent solvent extraction leaves the porous polymeric body of defined shape. The porous polymers have utility as medical prostheses, the porosity permitting ingrowth of neighboring tissue. A second material may be incorporated into the chambers, thereby creating a microstructure filling the voids of the macrostructure. A porous polymeric body manufactured by this process may incorporate biologically active agents, and which agents may be delivered in a time-staged delivery manner, where differing drugs may be delivered over differing periods.

Claims

1. A process for making a porous polymeric material, comprising the steps of:

a. selecting a polymer;

b. identifying a first solvent that is capable of substantially dissolving a solid form of the polymer;

c. identifying a second solvent that does not substantially dissolve the polymer in solid form, but instead merely swells the solid polymer;

d. providing at least sufficient first solvent to said polymer as to substantially dissolve the polymer in the first solvent to form a solution;

e. adding a quantity of the second solvent to the solution, whereupon an entire volume of solution begins to gel without forming a precipitate;

f. continuing the adding of the second solvent until a viscosity of the gel increases to a point where the gel is suitable for shape-forming;

g. shape-forming the gel; and

h. removing the first and second solvents from the gel.

4. The process of claim 1, wherein forming of the polymer gel comprises spreading the gel onto an open smooth or textured surface.

5. The process of claim 1, wherein forming of the polymer gel comprises injecting the gel into a mold.

6. The process of claim 1, wherein forming of the polymer gel comprises spreading or injecting the gel over a three-dimensional object, and removing the three-dimensional object after removing the first and second solvent from the gel.

7. The process of claim 1, wherein forming of the polymer gel involves inserting at least a portion of a three-dimensional object into a volume of the gel, and removing the three-dimensional object after removing the first and second solvent from the gel.

8. The process of claim 1, wherein, at least at some point during processing, at least one biologically active agent is mixed with the polymer and first solvent prior to addition of the second solvent.

9. The process of claim 8, wherein the biologically active agent is selected from one or more of the following:

physiologically acceptable drugs, surfactants, ceramics, hydroxyapatites, tricalciumphosphates, antithrombogenic agents, antibiotics, biologic modifiers, glycosaminoglycans, proteins, hormones, antigens, viruses, cells or cellular components.

10. The process of claim 1, wherein the gel is placed in contact with a separate body, after which the first and second solvent are removed, leaving the porous polymer mechanically bound to the body.

11. The process of claim 1, wherein the polymer comprises a polyurethane.

12. The process of claim 11, wherein said polyurethane is selected from siloxane-based polyurethanes and carbonate-based polyurethanes.

13. The process of claim 11, wherein the first solvent comprises at least one solvent selected from dimethyl acetimide and tetrahydrofuran.

14. The process of claim 11, wherein the first solvent comprises tetrahydrofuran, and the second solvent comprises at least one solvent selected from the group comprising p-dioxane and dimethyl sulfoxide.

29. The process of claim 1, wherein the polymer comprises at least one polymer selected from the group consisting of polyureas, polyethylenes, polyesters and fluoropolymers.

30. The method of claim 1, wherein said first solvent comprises an organic solvent selected from the group consisting of acetone, chloroform, p-dioxane, methylene chloride, n,n-dimethyl acetimide, dimethyl sulfoxide, 1-methyl-2-pyrrolidone, tetrahydro furan, toluene, m-xylene, o-xylene, and methyl-ethyl-ketone.

31. The method of claim 1, wherein said second solvent comprises an organic solvent selected from the group consisting of acetone, chloroform, p-dioxane, methylene chloride, n,n-dimethyl acetimide, dimethyl sulfoxide, 1-methyl-2-pyrrolidone, tetrahydrofuran, toluene, m-xylene, o-xylene, and methyl-ethyl-ketone.

33. The process of claim 1, wherein the porous polymeric body has a structure comprising a plurality of openings throughout its substance providing a highly convoluted intercommunicating network of chambers between its two surfaces, the walls of the chambers providing a large surface area, and wherein this structure is known as macrostructure, and further comprising adding a microstructure to said macrostructure, said adding comprising the steps of:

a. providing at least one biologically active agent in the form of a liquid to the pores of said porous polymeric body; and

b. freeze drying said liquid.

34. The process of claim 33, further comprising stabilizing said microstructure.

35. The process of claim 33, further comprising at least one different biologically active substance, said different biologically active substance being associated with said macro structure.

36. The process of claim 35, further comprising a time-staged or tiered delivery of said at least one biologically active substance and said at least one different biologically active substance from said porous polymeric body.

2. A process for making a porous polymeric material, comprising the steps of:

a. selecting a polymer;

b. identifying a first liquid that is capable of substantially completely dissolving a solid form of the polymer;

c. identifying a second liquid that does not substantially dissolve the polymer in solid form, but instead merely swells the solid polymer by being absorbed into its molecular structure, thereby increasing the mass of the polymer by at least about 35 percent by weight;

d. dissolving the polymer in the first liquid to form a solution;

e. adding a quantity of the second liquid to the solution, whereupon the entire volume of solution begins to gel without forming a precipitate;

f. continuing the adding of the second liquid until a viscosity of the gel increases to a point where the gel is suitable for shape-forming;

g. shape-forming the gel; and

h. removing the first and second liquids from the gel.

3. A process for making a porous polymeric material, comprising the steps of:

a. selecting a polymer;

b. identifying a first liquid that is capable of substantially completely dissolving a solid form of the polymer;

c. identifying a second liquid that does not substantially dissolve the polymer in solid form, but instead merely swells the solid polymer by being absorbed into its molecular structure, thereby increasing the mass of the polymer by at least about 35 percent by weight;

d. dissolving the polymer in the first liquid to form a solution;

e. adding a quantity of the second liquid to the solution, whereupon the entire volume of solution begins to increase in viscosity without visibly separating into multiple phases;

f. continuing the adding of the second liquid until the viscosity increases to a point where solution is suitable for shape-forming;

g. shape-forming the solution; and

h. removing at least the first liquid from the solution.

15. A process for creating a composite body comprising a porous polymeric body using a gel enhanced phase separation technique, the process comprising:

a. selecting a polymer for gelation;

b. identifying suitable first and second solvents for said polymer;

c. dissolving said polymer into said first solvent to form a solution having a quantity of polymer that will be appropriate for subsequent gelation;

d. adding a suitable second solvent to the solution that causes the solvent/polymer solution to thicken into a gel;

e. placing the gel in contact with at least one other material; and

f. removing the first and second solvent, thereby leaving a porous polymer and the at least one other material, wherein said porous polymer and said at least one other material are mechanically bound to each other.

16. The process of claim 15, wherein the other material is biodegradable.

17. The process of claim 15, wherein the other material provides reinforcement to the porous polymer.

18. The process of claim 17, wherein the other material is in the form of reinforcing threads.

19. The process of claim 15, wherein the other material is in the form of reinforcing rings.

20. The process of claim 15, wherein the porous polymeric body comprises a prosthesis, and further wherein said other material aids in attaching the porous polymer prosthesis to host tissue.

21. The process of claim 16, wherein the other material is in the form of a suture.

22. The process of claim 16, wherein the other material is in the form of a tack.

23. The process of claim 15, wherein the other material is a biologically active agent.

24. The process of claim 23, wherein the biologically active agent is selected from one or more of the following:

physiologically acceptable drugs, surfactants, ceramics, hydroxyapatites, tricalciumphosphates, antithrombogenic agents, antibiotics, biologic modifiers, glycosaminoglycans, proteins, hormones, antigens, viruses, cells or cellular components.

25. The process of claim 15, wherein the composite body is a component of a larger body.

26. The process of claim 15, wherein the selected polymer comprises a siloxane-based polyurethane.

27. The process of claim 26, wherein the first solvent comprises at least one solvent selected from the group comprising dimethyl acetimide, n-methyl pyrrolidinone and tetrahydrofuran.

28. The process of claim 26, wherein the first solvent comprises tetrahydrofuran, and the second solvent comprises at least one solvent selected from the group comprising p-dioxane, dimethyl sulfoxide and o-xylene.

32. A process for making a porous polymeric body, substantially as herein described in the specification and as shown in the drawings.