Rapidly degrading embolic particles with therapeutic agent release

• US 10,456,361 B2
• Filed: 02/05/2015
• Issued: 10/29/2019
• Est. Priority Date: 02/14/2014
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed, Inc. (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed, Inc. (Boston Scientific Corporation)
• Inventors: Kangas, Steven L.
• Primary Examiner(s): Worsham, Jessica
• Application Number:
  US14/614,928
• Publication Number:
  US 20150231075A1
• Time in Patent Office: 1,727 Days
• Field of Search: None
• 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
• 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,

(a) wherein said sub-particles comprise elongate particles having an aspect ratio ranging from 10:

1 to 1000;

1 that comprise said therapeutic agent and/or (b) wherein said sub-particles comprise particles that comprise an anti-tumor agent dispersed in oil,

wherein upon administration to a blood vessel, the matrix of the embolic particle biodegrades and the sub-particles remain localized in the blood vessel such that they continue to release therapeutic agent locally in the blood vessel after the matrix has completely degraded, and

wherein said sub-particles comprise said elongate particles having an aspect ratio ranging from 10;

1 to 1000;

1 that comprise said therapeutic agent.

4. The embolic particle of claim 1,

wherein said biodegradable polymer is selected from polyanhydrides, poly(ortho esters) and polysaccharides,

wherein upon administration to a blood vessel, the matrix of the particle completely biodegrades within a period of ranging from one hour to two days, and

wherein the sub-particles remain localized in the blood vessel and continue to release therapeutic agent locally in the blood vessel for a period of at least 7 days after the matrix has completely degraded.

6. The embolic particle of claim 1,

wherein said biodegradable polymer is selected from polyanhydrides, poly(ortho esters) and polysaccharides, and

wherein said sub-particles are paclitaxel crystals in the form of elongate particles having an aspect ratio ranging from 10:

1 to 1000;

1.

2. 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,

(a) wherein said sub-particles comprise elongate particles having an aspect ratio ranging from 10:

1 to 1000;

1 that comprise said therapeutic agent and/or (b) wherein said sub-particles comprise particles that comprise an anti-tumor agent dispersed in oil,

wherein upon administration to a blood vessel, the matrix of the embolic particle biodegrades and the sub-particles remain localized in the blood vessel such that they continue to release therapeutic agent locally in the blood vessel after the matrix has completely degraded, and

wherein said sub-particles comprise elongate particles having an aspect ratio ranging from 10;

1 to 1000;

1 of crystalline paclitaxel dihydrate.

5. The embolic particle of claim 2,

wherein said biodegradable polymer is selected from polyanhydrides, poly(ortho esters) and polysaccharides,

wherein upon administration to a blood vessel, the matrix of the particle completely biodegrades within a period of ranging from one hour to two days, and

wherein the sub-particles remain localized in the blood vessel and continue to release therapeutic agent locally in the blood vessel for a period of at least 7 days after the matrix has completely degraded.

3. A kit comprising:

(a) an injectable medical composition comprising embolic particles in wet or dry form, said embolic particles comprising sub-particles dispersed in a matrix that comprises a biodegradable polymer,

wherein the sub-particles comprise a therapeutic agent of low solubility,

wherein said sub-particles comprise elongate particles having an aspect ratio ranging from 10;

1 to 1000;

1 that comprise said therapeutic agent and/or wherein said sub-particles comprise particles that comprise an anti-tumor agent dispersed in oil, and

wherein upon administration to a blood vessel, the matrix of the embolic particle biodegrades and the sub-particles remain localized in the blood vessel such that they continue to release therapeutic agent locally in the blood vessel after the matrix has completely degraded, and

(b) one or more of the following;

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