LOADABLE POLYMERIC PARTICLES FOR THERAPEUTIC AND/OR DIAGNOSTIC APPLICATIONS AND METHODS OF PREPARING AND USING THE SAME

• US 20130052142A1
• Filed: 09/20/2012
• Published: 02/28/2013
• 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
• Granted Patent: US 9,511,153 B2
• Time in Patent Office: Days
• US Class Current: 424/9.411
• 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

1-8. -8. (canceled)

9. A method of minimizing blood flow to a tissue in a mammal comprising occluding at least a portion of a blood vessel of the mammal with at least one particle, wherein the particle comprises a poly[bis(trifluoroethoxy)phosphazene] and/or a derivative thereof.

10. The method according to claim 9, wherein the particle comprises a core and an outer coating, wherein the core comprises a hydrogel formed from an acrylic-based polymer and the outer coating comprises poly[bis(trifluoroethoxy)phosphazene] and/or a derivative thereof.

11. The method according to claim 10, wherein the particle core further comprises barium sulfate as coating and/or absorbed within the core.

12. A method of delivering an active agent to a localized area within a body of a mammal comprising contacting the localized area with at least one of a particle comprising poly[bis(trifluoroethoxy)phosphazene] and/or a derivative thereof and an active agent, such that an effective amount of the active agent is exposed to the localized area.

13. The method according to claim 12, wherein the particle comprises a core and an outer coating and the active agent is delivered through the outer coating, and wherein the outer coating comprises poly[bis(trifluoroethoxy)phosphazene] and/or a derivative thereof.

14. The method according to claim 13, wherein the particle core further comprises barium sulfate as coating and/or absorbed within the core.

15. The method according to claim 12, wherein the particle comprises a hydrogel acrylic-based polymer core and an outer coating, and the active agent is delivered in the core and diffuses through the outer coating, and wherein the outer coating comprises poly[bis(trifluoroethoxy)phosphazene] and/or a derivative thereof.

16-17. -17. (canceled)

19. A method of tracing the passage of a particle through a blood vessel in a mammal, the method comprising injecting into the bloodstream of a mammal at least one tracer particle, the tracer particle comprising poly[bis(trifluoroethoxy)phosphazene] and/or a derivative thereof and a contrast agent, and imaging the route of the particle.

20. The method according to claim 19, wherein the tracer particle comprises a core and a coating surrounding the core, wherein the coating comprises poly[bis(trifluoroethoxy)phosphazene] and/or a derivative thereof and the core comprises an acrylic-based polymer hydrogel.

21. The method according to claim 20, wherein the particle core further comprises barium sulfate as coating and/or diffused within the core.

22. The method according to claim 19, wherein the contrast agent is selected from the group consisting of barium sulfate, tantalum compounds, gadolinium compounds and iodine-containing compounds.

23. A method of enhanced ultrasound imaging comprising administering to an ultrasound subject at least one hollow microcapsule comprising poly[bis(trifluoroethoxy)phosphazene] and/or a derivative thereof to an area of the ultrasound subject, and imaging the area of the subject using ultrasound.

24. A method of delivering an active agent to a localized area within the body of a mammal comprising contacting the localized area with at least one of a particle comprising poly[bis(trifluoroethoxy)phosphazene] and/or a derivative thereof and an active agent, such that an effective amount of the active agent is exposed to the localized area, wherein the particle comprises an agent to increase density.

25. The method according to claim 24, wherein the agent to increase density is selected from the group consisting of deuterium oxide, cesium, at least one organic dye, barium sulfate, and combinations thereof.

26. The method according to claim 24, wherein the particle comprises an outer coating and a core, wherein the outer coating comprises poly[bis(trifluoroethoxy)phosphazene] and/or a derivative thereof and the core comprises an acrylic-based polymer hydrogel, wherein the particle is pre-treated with cesium chloride to provide cesium to the particle.

27. The method according to claim 24, wherein the particle comprises an outer coating and a core, wherein the outer coating comprises poly[bis(trifluoroethoxy)phosphazene] and/or a derivative thereof and the core comprises an acrylic-based polymer hydrogel and barium sulfate.

28. The method according to claim 27, wherein the barium sulfate is present as a coating on the core.

29. The method according to claim 27, wherein the barium sulfate is diffused within the core.

30. A method for minimizing agglomeration and/or aggregation of particles formed from acrylic-based polymers, comprising providing barium sulfate to the core and/or surface of the particles.

31. The method according to claim 30, wherein the particles comprise and outer coating of poly[bis(trifluoroethoxy)phosphazene] and/or a derivative thereof and the method further comprises minimizing damage to the outer coating.