Loadable polymeric particles for therapeutic and/or diagnostic applications and methods of preparing and using the same

• US 8,318,209 B2
• Filed: 10/25/2005
• Issued: 11/27/2012
• Est. Priority Date: 10/25/2004
• Status: Active Grant

• Current Assignee: Varian Medical Systems Incorporated (Siemens AG)
• Original Assignee: CeloNova Biosciences Germany GmbH (Boston Scientific Corporation)
• Inventors: Harder, Philipp, Fritz, Olaf, Fritz, Ulf
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): SCHLIENTZ, LEAH H
• Application Number:
  US11/257,535
• Publication Number:
  US 20060088476A1
• Time in Patent Office: 2,590 Days
• Field of Search: 424/408, 424/417, 424/9.41, 424/9.411, 424/489, 424/490, 424/497, 424/9.4, 424/422, 424/423, 528/399
• US Class Current: 424/497
• CPC Class Codes: A61K 49/0404 containing barium sulfate
• CPC Class Codes: A61K 49/0419 Microparticles, microbeads, microcapsules, microspheres, i.e. having a size or diameter higher or equal to 1 micrometer
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• 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 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid

Abstract

Particles are provided for use in therapeutic and/or diagnostic procedures. The particles include poly[bis(trifluoroethoxy) phosphazene] and/or a derivatives thereof which may be present throughout the particles or within an outer coating of the particles. The particles can also include a core having a hydrogel formed from an acrylic-based polymer. Barium sulfate may also be provided to the core of the particles as a coating or absorbed within the core of the particles. The particles can be used to minimize blood flow to mammalian tissues by occluding at least a portion of a blood vessel of the mammal, or to deliver an active agent to a localized area within a body of a mammal by contacting a localized area with at least one of the particles. Further, the particles are useful in sustained release formulations including active agent(s) for oral administration, as tracer particles for injection into the bloodstream of a mammal or for use in enhanced ultrasound imaging. The particles may include agents for increasing density for achieving useful buoyancy levels in suspension.

Claims

1. A porous non-degradable particle for use in a therapeutic and/or diagnostic procedure, the porous non-degradable particle comprising:

a core comprising a hydrogel formed from acrylic-based polymers derived from mono-functional acrylic-based monomer units forming the backbone of the hydrogel polymers and multi-functional monomer units forming covalent cross-links within the hydrogel polymers; and

an outer coating comprising poly[bis(trifluoroethoxy) phosphazene] derivative of formula (I)

2. The porous non-degradable particle of claim 1, wherein the porous particle further comprises an agent for increasing density of the particle.

3. The porous non-degradable particle of claim 2, wherein the agent is selected from the group consisting of deuterium oxide, cesium, organic dye, barium sulfate, and combinations thereof.

8. A formulation for minimizing blood flow to a tissue in a mammal comprising one or more porous non-degradable particles of claim 1 to occlude at least a portion of a blood vessel of the mammal.

9. The formulation of claim 8, wherein the porous non-degradable particle further comprises a contrast agent is selected from the group consisting of barium sulfate, tantalum compounds, gadolinium compounds and iodine-containing compounds.

10. The formulation of claim 8, wherein the polyphosphazene polymer of the outer coating is poly[bis(2,2,2-trifluoroethoxy)phosphazene].

11. A formulation for delivering an active agent to a localized area within a body of a mammal, comprising one or more porous non-degradable particles of claim 1;

and an active agent.

12. The formulation of claim 11, wherein the porous non-degradable particle further comprises a contrast agent selected from the group consisting of barium sulfate, tantalum compounds, gadolinium compounds and iodine-containing containing compounds.

13. The formulation of claim 11, wherein the polyphosphazene polymer of the outer coating is poly[bis(2,2,2-trifluoroethoxy)phosphazene].

14. A diagnostic formulation for tracing the passage of a porous particle through a blood vessel, comprising:

one or more porous non-degradable particles of claim 1; and

an contrast agent.

15. The diagnostic formulation of claim 14, wherein the contrast agent is selected from the group consisting of barium sulfate, tantalum compounds, gadolinium compounds and iodine-containing compounds.

16. The diagnostic formulation of claim 14, wherein the polyphosphazene polymer of the outer coating is poly[bis(2,2,2-trifluoroethoxy)phosphazene].

17. A diagnostic formulation for tracing the passage of a porous particle through a blood vessel, comprising:

one or more porous non-degradable particles of claim 1; and

an contrast agent.

18. The diagnostic formulation of claim 17, wherein the contrast agent is selected from the group consisting of barium sulfate, tantalum compounds, gadolinium compounds and iodine-containing compounds.

19. The diagnostic formulation of claim 17, wherein the polyphosphazene polymer of the outer coating is poly[bis(2,2,2-trifluoroethoxy)phosphazene].

20. The porous non-degradable particle of claim 1, wherein the polyphosphazene polymer of the outer coating is poly[bis(2,2,2-trifluoroethoxy)phosphazene].

4. A sustained release formulation of an active agent for oral administration, comprising:

an active agent; and

porous non-degradable particles comprising

a core comprising a hydrogel formed from acrylic-based polymers derived from mono-functional acrylic-based monomer units forming the backbone of the hydrogel polymers and multi-functional monomer units forming covalent cross-links within the hydrogel polymers; and

an outer coating comprising poly[bis(trifluoroethoxy) phosphazene] derivative of formula (I)

5. The sustained release formulation of claim 4, wherein the porous non-degradable particle further comprises an agent for increasing density of the particle.

6. The sustained release formulation of claim 5, wherein the agent is selected from the group consisting of deuterium oxide, cesium, organic dye, barium sulfate, and combinations thereof.

7. The sustained release formulation of claim 4, wherein the polyphosphazene polymer of the outer coating is poly[bis(2,2,2-trifluoroethoxy)phosphazene].

21. A porous non-degradable particle for use in a therapeutic and/or diagnostic procedure, the porous non-degradable particle comprising:

a core comprising a hydrogel formed from acrylic-based polymers derived from mono-functional acrylic-based monomer units forming the backbone of the hydrogel polymers and multi-functional monomer units forming covalent cross-links within the hydrogel polymers; and

an outer coating comprising poly[bis(trifluoroethoxy) phosphazene] derivative of formula (I)