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

Patent metadata

Field	Value
Publication number	US-11052050-B2
Application number	US-201615351973-A
Country	US
Kind code	B2
Filing date	Nov 15, 2016
Priority date	Oct 25, 2004
Publication date	Jul 6, 2021
Grant date	Jul 6, 2021

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. Farther, 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.

First claim

We claim:

1. A method of minimizing blood flow to a tissue in a mammal comprising occluding at least a portion of a blood vessel leading to the tissue with at least one particle, 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.

2. The method according to claim 1 , further comprising the step of delivering at least one active agent to the tissue with the particle as part of the occluding step.

3. The method according to claim 2 , wherein the at least one active agent is a cytostatic agent, an anti-inflammatory agent, an anti-mitogenic or cell proliferation active agent, an antineoplastic agent, a receptor-blocking agent, a steroid, or a hormone.

4. The method according to claim 1 , wherein the particle is porous and non-degradable.

5. The method according to claim 1 , wherein the core further comprises barium sulfate as a coating on the core and/or absorbed within the core.

6. 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 particle comprising a hydrogel acrylic-based polymer core, an outer coating comprising poly [bis (trifluoroethoxy) phosphazene] and/or a derivative thereof, and at least one active agent, such that an effective amount of the active agent is exposed to the localized area.

7. The method according to claim 6 , wherein the at least one active agent is a cytostatic agent, an anti-inflammatory agent, an anti-mitogenic or cell proliferation active agent, an antineoplastic agent, a receptor-blocking agent, a steroid, or a hormone.

8. The method according to claim 6 , wherein the active agent is delivered through the outer coating, and wherein the outer coating comprises the poly [bis (trifluoroethoxy) phosphazene] and/or a derivative thereof.

9. The method according to claim 8 , wherein the core further comprises barium sulfate as a coating on the core and/or absorbed within the core.

10. The method according to claim 6 , wherein the active agent is delivered in the core and diffuses through the outer coating.

11. The method according to claim 6 , wherein the particle is delivered in a formulation including a contrast agent selected from the group consisting of barium sulfate, tantalum compounds, gadolinium compounds and iodine-containing compounds.

12. 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 particle comprising an outer coating comprising poly [bis (trifluoroethoxy) phosphazene] and/or a derivative thereof, a core comprising an acrylic-based polymer hydrogel, and at least one 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.

13. The method according to claim 12 , 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.

14. The method according to claim 12 , wherein the at least one active agent is a cytostatic agent, an anti-inflammatory agent, an anti-mitogenic or cell proliferation active agent, an antineoplastic agent, a receptor-blocking agent, a steroid, or a hormone.

15. The method according to claim 12 , wherein the particle is pre-treated with cesium chloride to provide cesium to the particle.

16. The method according to claim 12 , wherein the core further comprises barium sulfate.

17. The method according to claim 16 , wherein the barium sulfate is present as a coating on the core.

18. The method according to claim 16 , wherein the barium sulfate is diffused within the core.

Assignees

• Varian Med Sys Inc

Inventors

• Harder Philipp
• Fritz Olaf
• Fritz Ulf

Classifications

• A61K49/22

  Echographic preparations; Ultrasonic imaging preparations · CPC title

• A61K9/50

  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 title

• A61K49/04

  X-ray contrast preparations · CPC title

• A61K9/16 Primary

  Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)} · CPC title

• A61K9/5073

  having two or more different coatings optionally including drug-containing subcoatings · CPC title