PARTICLES FOR INJECTION AND PROCESSES FOR FORMING THE SAME

• US 20090169471A1
• Filed: 12/19/2008
• Published: 07/02/2009
• Est. Priority Date: 12/28/2007
• Status: Abandoned Application

• Current Assignee: Boston Scientific Scimed, Inc. (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed, Inc. (Boston Scientific Corporation)
• Inventors: Richard, Robert E., O'Gara, John E., Puri, Sonali
• Application Number:
  US12/339,588
• Publication Number:
  US 20090169471A1
• Time in Patent Office: Days
• US Class Current: 424/1.290
• CPC Class Codes: A61K 47/6921 the form being a particulate, a powder, an adsorbate, a bead or a sphere
• CPC Class Codes: A61K 51/1251 micro- or nanospheres, micro- or nanobeads, micro- or nanocapsules
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/418 Agents promoting blood coagulation, blood-clotting agents, embolising agents
• CPC Class Codes: A61L 2300/44 Radioisotopes, radionuclides
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• 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
• CPC Class Codes: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids

Abstract

According to an aspect of the invention, injectable particles are provided that include (a) porous polymeric particles that contain at least one type of particle-forming polymer and (b) a pore-filling composition that includes at least one therapeutic agent and at least one pore-filling polymer. The pore-filling composition at least partially fills the pores of the injectable porous polymeric particles. Other aspects of the invention pertain to methods of making such particles.

Still other aspects of the invention pertain to injectable compositions that comprise such particles and to methods of treatment that employ such injectable compositions.

Claims

1. Injectable particles comprising (a) porous polymeric particles that comprise a particle-forming polymer and (b) a composition that comprises a therapeutic agent and a pore-filling polymer, said composition at least partially filling the pores of the injectable porous polymeric particles, wherein the particle-forming polymer may the same as or different from the pore-filling polymer.

2. The injectable particles of claim 1, wherein 95 vol % of said particles have a longest linear cross-sectional dimension between 40 μ

m and 5000 μ

m.

3. The injectable particles of claim 1, wherein said particles are spherical.

4. The injectable particles of claim 3, wherein 95 vol % of said particles have a longest linear cross-sectional dimension between 40 μ

m and 5000 μ

m.

5. The injectable particles of claim 1, wherein said particles are non-spherical.

6. The injectable particles of claim 5, wherein 95 vol % of said particles have a longest linear cross-sectional dimension between 40 μ

m and 5000 μ

m.

7. The injectable particles of claim 1, wherein said particles comprise pores ranging from 0.5 to 100 μ

m in width.

8. The injectable particles of claim 1, wherein said porous polymeric particles are biostable.

9. The injectable particles of claim 1, wherein said porous polymeric particles are biodisintegrable.

10. The injectable particles of claim 1, wherein said porous polymeric particles are hydrogel particles.

11. The injectable particles of claim 10, wherein said porous polymeric particles comprise crosslinked polyvinyl alcohol as a particle-forming polymer.

12. The injectable particles of claim 1, wherein said therapeutic agent is selected from toxins, antineoplastic agents, ablation agents, proinflammatory agents and sclerosing agents.

13. The injectable particles of claim 1, wherein said pore-filling polymer is biostable.

14. The injectable particles of claim 1, wherein said pore-filling polymer is biodisintegrable.

15. The injectable particles of claim 1, wherein said pore-filling polymer is hydrophobic and the therapeutic agent is hydrophobic.

16. The injectable particles of claim 1, wherein said pore-filling polymer is an amphiphilic and the therapeutic agent is hydrophobic.

17. The injectable particles of claim 1, wherein said pore-filling polymer is hydrophilic and the therapeutic agent is hydrophilic.

18. The injectable particles of claim 1, wherein said therapeutic agent is charged and the pore-filling polymer non-covalently binds to the therapeutic agent by electrostatic interactions.

19. The injectable particles of claim 18, wherein said therapeutic agent is a charged radioisotope and the pore-filling polymer comprises ligands that form a coordination complex with the charged radioisotope.

20. The injectable particles of claim 18, wherein said therapeutic agent is a charged organic compound and the pore-filling polymer comprises a net charge that is opposite to that of the charged organic compound.

21. The injectable particles of claim 17, wherein said pore-filling polymer comprises pendant groups selected from —

COO⁻

groups, —

SO₃⁻

groups, —

PO₂(OH)⁻

groups, —

NH₃ groups, ═

NH₂⁺ groups, ═

NH⁺—

groups, ═

N⁻

═

groups, and combinations thereof.

22. An injectable medical composition comprising the particles of claim 1.

23. The injectable medical composition of claim 22, comprising a tonicity adjusting agent.

24. The injectable medical composition of claim 23, wherein said tonicity adjusting agent is selected from sugars, polyhydric alcohols, inorganic salts and combinations thereof.

25. The injectable medical composition of claim 22, wherein said injectable medical composition is disposed within a glass container or a preloaded syringe.

26. A method of forming the injectable particles of claim 1, comprising exposing porous polymeric particles to a solution comprising said therapeutic agent and said pore-filling polymer.

27. The method of claim 26, wherein wet or dry porous polymeric particles are exposed to said solution.

28. A method of forming the injectable particles of claim 1, comprising (a) exposing porous polymeric particles to a solution comprising said pore-filling polymer and (b) exposing the resulting particles to a solution comprising said therapeutic agent.