Particle-containing complex porous materials

• US 20060246121A1
• Filed: 04/25/2006
• Published: 11/02/2006
• Est. Priority Date: 04/27/2005
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Wei, Guobao, Ma, Peter X.
• Granted Patent: US 8,268,344 B2
• Time in Patent Office: Days
• US Class Current: 424/443
• CPC Class Codes: A61K 48/0008 characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1658 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5161 Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
• CPC Class Codes: A61K 9/5169 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/258 Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 2300/624 Nanocapsules
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges

Abstract

Porous materials and methods for forming them are disclosed. One method for immobilizing micro-particles and/or nano-particles onto internal pore surfaces and/or external pore surfaces of porous materials includes suspending the micro-particles and/or nano-particles in a liquid adapted to swell, soften, and/or deform either the porous materials and/or the particles, thereby forming a liquid-particle suspension. The method further includes adding the suspension to the porous materials; and removing the liquid, thereby forming the porous materials having the micro-particles and/or nano-particles immobilized on the internal pore surfaces and/or the external pore surfaces.

Claims

1. A method for immobilizing at least one of micro-particles or nano-particles onto at least one of internal pore surfaces or external pore surfaces of porous materials, the method comprising:

suspending the at least one of micro-particles or nano-particles in a non-solvent of both the porous materials and the at least one of micro-particles or nano-particles, thereby forming a non-solvent-particle suspension;

adding the suspension to the porous materials;

removing the non-solvent to form the porous materials having the at least one of micro-particles or nano-particles loosely adhered on at least one of the internal pore surfaces or the external pore surfaces;

at least one of swelling, deforming, or slightly dissolving at least one of the porous materials or the at least one of micro-particles or nano-particles by addition of a liquid adapted to perform the at least one of swelling, deforming or slightly dissolving; and

removing the liquid, thereby forming the porous materials having the at least one of micro-particles or nano-particles immobilized on the at least one of the internal pore surfaces or the external pore surfaces.

2. The method as defined in claim 1 wherein the at least one of the micro-particles or the nano-particles is selected from natural materials, synthetic materials, organic materials, inorganic materials, metallic materials, composites thereof, and combinations thereof.

3. The method as defined in claim 1 wherein the at least one of the micro-particles or nano-particles is a controlled release particle having an agent embedded therein.

4. The method as defined in claim 3 wherein the agent is selected from proteins, hormones, DNA, RNA, nutrients, drugs, biologically regulating agents, and combinations thereof.

5. The method as defined in claim 3 wherein, prior to suspending the at least one of the micro-particles or nano-particles, the method further comprises varying at least one property of the at least one of the micro-particles or nano-particles, thereby altering at least one release characteristic of the agent.

6. The method as defined in claim 1 wherein removing the liquid is accomplished by at least one of freeze-drying, vacuum drying, evaporation, or exchange with a non-solvent of the particles and the porous material.

30. Porous materials formed by the method of claim 1.

7. A method for immobilizing at least one of micro-particles or nano-particles onto at least one of internal pore surfaces or external pore surfaces of porous materials, the method comprising:

suspending the at least one of micro-particles or nano-particles in a liquid adapted to at least one of swell, soften, and deform at least one of the porous materials and the at least one of micro-particles or nano-particles, thereby forming a liquid-particle suspension;

adding the suspension to the porous materials; and

removing the liquid, thereby forming the porous materials having the at least one of the micro-particles or nano-particles immobilized on the at least one of the internal pore surfaces or the external pore surfaces.

8. The method as defined in claim 7 wherein the at least one of the micro-particles or the nano-particles is selected from natural materials, synthetic materials, organic materials, inorganic materials, metallic materials, composites thereof, and combinations thereof.

9. The method as defined in claim 7 wherein the at least one of the micro-particles or nano-particles is a controlled release particle having an agent embedded therein.

10. The method as defined in claim 9 wherein the agent is selected from proteins, hormones, DNA, RNA, nutrients, drugs, biologically regulating agents, and combinations thereof.

11. The method as defined in claim 9 wherein, prior to suspending the at least one of the micro-particles or nano-particles, the method further comprises varying at least one property of the at least one of the micro-particles or nano-particles, thereby altering at least one release characteristic of the agent.

12. The method as defined in claim 7 wherein removing the liquid is accomplished by at least one of freeze-drying, vacuum drying, evaporation, or exchange with a non-solvent of the particles and the porous material.

31. Porous materials formed by the method of claim 7.

13. A method for forming a porous material, comprising:

coating a suspension or mixture of at least one of micro-particles or nano-particles onto a negative replica of a desired macroporous architecture of the porous material, thereby forming a coated replica, the negative replica having been formed from a predetermined three-dimensional configuration of shaped porogen materials;

removing a liquid into which the at least one of the micro-particles or nano-particles was suspended or mixed;

casting a second liquid onto the coated replica, thereby forming a system;

removing volatile components from the system, thereby forming a complex material including the replica, the at least one of micro-particles and nano-particles, and non-volatile components of the cast, second liquid; and

removing the porogen materials from the complex material, thereby forming the porous material having the desired three-dimensional macroporous architecture with the at least one of micro-particles and nano-particles immobilized on interior pore surfaces thereof.

14. The method as defined in claim 13 wherein the second liquid is selected from a polymer solution, a polymer suspension, a non-polymer solution, a non-polymer suspension, and combinations thereof.

15. The method as defined in claim 13 wherein the negative replica is formed of at least one material selected from gelatins, collagen, proteins, polypeptides, carbohydrates, polysaccharides, alginate, chitin, chitosan, pectin, salts, sodium hydroxide, sugars, waxes, naphthalene, natural or synthetic water soluble polymers, natural or synthetic non-water soluble polymers, degradable polymers, non-degradable polymers, partially degradable polymers, and combinations thereof.

16. The method as defined in claim 13 wherein removing the volatile components is accomplished by evaporation, freeze-drying, sublimation, extraction, and combinations thereof.

17. The method as defined in claim 13 wherein removing the porogen materials is accomplished by dissolution in a solvent, melting, degrading, and combinations thereof.

18. The method as defined in claim 13 wherein the at least one of the micro-particles or the nano-particles is selected from natural materials, synthetic materials, organic materials, inorganic materials, metallic materials, composites thereof, and combinations thereof.

19. The method as defined in claim 18 wherein the at least one of the micro-particles or nano-particles is a controlled release particle having an agent embedded therein.

20. The method as defined in claim 19 wherein the agent is selected from proteins, hormones, DNA, RNA, nutrients, drugs, biologically regulating agents, and combinations thereof.

32. Porous materials formed by the method of claim 13.

21. A method of making porous foam materials, comprising:

suspending at least one of micro-particles and nano-particles in a solution of solvent and materials adapted to form the porous foam materials, the solvent substantially not dissolving the at least one of micro-particles and nano-particles, thereby forming a solution-particles suspension;

casting the suspension into a mold or on a template of the porous foam materials; and

removing the solvent, thereby forming the porous foam materials having the at least one of micro-particles and nano-particles entrapped in or on walls of the porous foam materials.

22. The method as defined in claim 21 wherein the at least one of the micro-particles or the nano-particles is selected from natural materials, synthetic materials, organic materials, inorganic materials, metallic materials, composites thereof, and combinations thereof.

23. The method as defined in claim 21 wherein the at least one of the micro-particles or nano-particles is a controlled release particle having an agent embedded therein.

24. The method as defined in claim 23 wherein the agent is selected from proteins, hormones, DNA, RNA, nutrients, drugs, biologically regulating agents, and combinations thereof.

25. The method as defined in claim 21 wherein removing the solvent is accomplished by at least one of freeze-drying, vacuum drying, evaporation, or exchange with a non-solvent of the particles and the porous material.

33. Porous foam materials formed by the method of claim 21.

26. A material capable of controllably releasing a biologically active agent, comprising:

a porous material having internal pore surfaces and external pore surfaces; and

at least one of micro-particles or nano-particles immobilized onto at least one of the internal pore surfaces or the external pore surfaces, the at least one of the micro-particles or nano-particles having a biologically active agent substantially embedded therein.

27. The material as defined in claim 26 wherein the porous material has a porosity of at least 30%.

28. The material as defined in claim 26 wherein the at least one of the micro-particles or the nano-particles is selected from natural materials, synthetic materials, organic materials, inorganic materials, metallic materials, composites thereof, and combinations thereof.

29. The material as defined in claim 26 wherein the biologically active agent is selected from proteins, hormones, DNA, RNA, nutrients, drugs, biologically regulating agents, and combinations thereof.

34. A method for forming a sugar sphere, comprising:

melting a sugar material, thereby forming a liquefied sugar material;

emulsifying the liquefied sugar material, thereby forming a sugar material emulsion; and

solidifying the sugar material emulsion, thereby forming sugar spheres.

35. The method as defined in claim 34 wherein the sugar material is selected from sucrose, maltose, dextrose, fructose, and combinations thereof.

36. The method as defined in claim 34 wherein the sugar material is emulsified in a non-solvent to the sugar material.

37. The method as defined in claim 34, further comprising rinsing the sugar spheres.

38. The method as defined in claim 34 wherein the sugar spheres have a size ranging from about 20 μ

m to about 2 mm.

39. A method for using the sugar spheres as defined in claim 34, comprising:

packaging a plurality of sugar spheres in a mold contained in a substantially non-hydrous environment; and

treating the plurality of sugar spheres at a predetermined temperature for a predetermine time sufficient to bond the plurality of sugar spheres together in a predetermined configuration.

40. The method as defined in claim 39 wherein the predetermined temperature ranges from about room temperature to about 100°

C.