RAPIDLY DEGRADING EMBOLIC PARTICLES WITH THERAPEUTIC AGENT RELEASE

• US 20150231075A1
• Filed: 02/05/2015
• Published: 08/20/2015
• Est. Priority Date: 02/14/2014
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: KANGAS, Steven L.
• Granted Patent: US 10,456,361 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/0042 Materials resorbable by the body
• CPC Class Codes: A61L 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices artificial blood vessels A61L27/507
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

In accordance with one aspect, embolic particles are provided which comprise sub-particles that comprise a therapeutic agent of low solubility dispersed in a matrix that comprises a biodegradable polymer. Other aspects pertain to injectable compositions that comprise such particles and to methods of treatment that employ such injectable compositions. Still other aspects pertain to methods of making such particles.

Claims

1. An embolic particle comprising sub-particles dispersed in a matrix that comprises a biodegradable polymer, wherein the sub-particles comprise a therapeutic agent of low solubility.

2. The embolic particle of claim 1, wherein upon administration to a blood vessel, the particle completely biodegrades within a period of one hour to two days.

3. The embolic particle of claim 1, wherein said particle ranges between 20 and 200 microns in width.

4. The embolic particle of claim 1, wherein said sub-particle range between 10 nm and 10,000 nm in width.

5. The embolic particle of claim 1, wherein said biodegradable polymer is selected from polyanhydrides, poly(ortho esters) and polysaccharides.

6. The embolic particle of claim 1, wherein said biodegradable polymer comprises starch and wherein the starch is crosslinked to stabilize the embolic particle.

7. The embolic particle of claim 1, wherein said sub-particles comprise needle-like particles that comprise said therapeutic agent.

8. The embolic particle of claim 1, wherein said sub-particles comprise particles of amorphous paclitaxel, particles of crystalline anhydrous paclitaxel or needle-like particles of crystalline paclitaxel dihydrate.

9. The embolic particle of claim 1, wherein said sub-particles comprise particles that comprise an anti-tumor agent dispersed in oil.

10. The embolic particle of claim 1, wherein said sub-particles comprise crystalline paclitaxel particles dispersed in iodinated oil.

11. The embolic particle of claim 1, wherein said sub-particles comprise crystalline paclitaxel particles dispersed in iodinated poppy seed oil.

12. The embolic particle of claim 1, wherein said sub-particles comprise protein stabilized particles that comprise an anti-tumor agent.

13. The embolic particle of claim 1, wherein said sub-particles comprise protein stabilized paclitaxel particles.

14. The embolic particle of claim 1, wherein said sub-particles comprise albumen stabilized paclitaxel particles.

15. An injectable medical composition comprising embolic particles in accordance with claim 1 in wet or dry form.

16. The injectable medical composition of claim 15, further comprising a tonicity adjusting agent.

17. The injectable medical composition of claim 15, wherein said injectable medical composition is disposed within a glass container or a preloaded medical device.

18. A method of embolization comprising injecting the injectable medical composition of claim 15 into a patient.

19. The method of embolization of claim 18, further comprising administering an anticoagulant to the patient.

20. A kit comprising:

(a) the medical composition of claim 15 and (b) one or more of the following;

(i) a catheter, (ii) a guidewire and (iii) a liquid carrier.