MICROSPHERES

• US 20100247663A1
• Filed: 06/20/2008
• Published: 09/30/2010
• Est. Priority Date: 06/20/2007
• Status: Active Grant

• Current Assignee: UCL Business PLC (University of London)
• Original Assignee: Kings College London (University of London)
• Inventors: Day, Richard Michael, Blaker, Jonny
• Granted Patent: US 8,765,182 B2
• Time in Patent Office: Days
• US Class Current: 424/497
• CPC Class Codes: A01K 2207/20 Animals treated with compounds which are neither proteins nor nucleic acids
• 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 9/1682 Processes
• 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 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61K 9/50 Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: C08J 2201/0544 the non-solvent being aqueous
• 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: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]
• CPC Class Codes: Y10T 428/2989 Microcapsule with solid core [includes liposome]

Abstract

The invention relates to the production of microspheres having radial pores using thermally induced phase separation, especially microspheres for use in tissue engineering.

Claims

1. A microsphere having radial pores.

2. A microsphere according to claim 1, wherein the microsphere is about 10 to 2000 μ

m diameter.

3. A microsphere according to claim 1, wherein the microsphere is less than 300 μ

m in diameter.

4. A microsphere according to claim 1, wherein the pores are between 1 and 100 μ

m in diameter.

5. A microsphere according to claim 1, wherein the microsphere includes a skin region at its surface.

6. A microsphere according to claim 1, wherein the microsphere is skinless.

7. A microsphere according to claim 1, wherein the microsphere is produced from a polymer.

8. A microsphere according to claim 7, wherein the polymer is pharmaceutically acceptable.

9. A micro sphere according to claim 7, wherein the polymer is degradable.

10. A microsphere according to claim 7, wherein the polymer is non-degradable.

11. A microsphere according to claim 7, wherein the polymer is synthetic.

12. A microsphere according to claim 7, wherein the polymer is non-synthetic.

13. A microsphere according to claim 7, wherein the polymer is a combination of a synthetic polymer and a non-synthetic polymer.

14. A microsphere according to claim 7, wherein the polymer is a copolymer.

15. A microsphere according to claim 11, wherein the polymer is a poly(α

-hydroxyester), polyanhydride, polyorthoester, polyphosphazne, polypropylene fumarate, poly propylene-fumarate-co-ethylene glycol), polyethylene oxide, polyhydroxybutyrate (PHB) and polyhydroxyvalerate (PHV), a co-polymer of PHB and PHV, or a poly(α

-hydroxyester)-co-PEG copolymer.

16. A microsphere according to claim 12, wherein the polymer is fibrin.

17. A microsphere according to claim 1, wherein the microsphere contains an encapsulated additive.

18. A microsphere according to claim 17, wherein the additive is a glass, glass-ceramic, or ceramic, wherein the glass, glass-ceramic, or ceramic contains NaH₂PO₄, CaCO₃, P₂0₅, or Ag₂SO₄;

proteins or peptides such as antibodies or fragments thereof;

nucleic acids;

or therapeutic agents.

19. A microsphere according to claim 1, wherein the microsphere was produced by thermally induced phase separation.

31. A method of treating a wound, comprising filling the wound with microspheres according to claim 1.

20. A method of producing microspheres comprising the steps of:

a) dissolving a polymer in a solvent to form a solution;

b) quenching droplets of the solution in a quenching fluid; and

c) freeze-drying the resulting spheres.

21. A method according to claim 20, wherein the solvent is selected from dimethylcarbonate, chloroform, acetone, dimethylchloride, tetrahydrofuran and supercritical carbon dioxide.

22. A method according to claim 20, wherein the solution is introduced into the quench using a syringe, a vibrating needle or an atomiser.

23. A method according to claim 20, further comprising the step of sonicating the solution.

25. A method according to claim 20 or 24, additionally comprising the step of mixing the polymer with an additive to be encapsulated within the microspheres.

26. A method according to claim 20 or 25, additionally comprising including a further phase in the solution.

27. A method according to claim 26, wherein the further phase is selected from water ice microparticulates, salt, sucrose, paraffin wax, citric acid and sodium bicarbonate.

28. A microsphere produced by the method of claim 20 or

24. A method of producing a microsphere comprising the steps of:

a) dissolving a polymer in a solvent to form a solution;

b) agitating or homogenising the solution in water;

c) freeze-drying the resulting spheres.

29-30. -30. (canceled)