Multi-encapsulated formulations made with oxidized cellulose

Patent metadata

Field	Value
Publication number	US-9919063-B2
Application number	US-201314424464-A
Country	US
Kind code	B2
Filing date	Sep 17, 2013
Priority date	May 31, 2012
Publication date	Mar 20, 2018
Grant date	Mar 20, 2018

Abstract

A microsphere and method for forming the same are disclosed. The microsphere includes modified cellulose and at least one of a visualization agent, a magnetic material, or a radioactive material.

First claim

What is claimed is:

1. A method comprising:
forming an oxidized cellulose solution by contacting an oxidized cellulose with a solvent under an inert atmosphere to form a swelled oxidized cellulose mixture;
adjusting the swelled oxidized cellulose mixture to a first temperature;
contacting the swelled oxidized cellulose mixture with a salt under the inert atmosphere to form an oxidized cellulose solution;
adjusting the oxidized cellulose solution to a second temperature;
contacting the oxidized cellulose solution with at least one visualization agent to form a discontinuous phase liquid;
contacting the discontinuous phase liquid with a continuous phase liquid to form an emulsion; and
contacting the emulsion with a third phase liquid to extract the solvent from the emulsion thereby forming a plurality of microspheres.

2. The method according to claim 1 , wherein the third phase liquid is miscible with the continuous composition and the discontinuous composition.

3. The method according to claim 2 , wherein the third phase liquid is selected from the group consisting of isopropyl myristate, hexane, triglycerides and combinations thereof.

4. The method according to claim 1 , wherein the third phase liquid is present in an amount from about 300% by volume to about 200% by volume of the continuous phase liquid.

5. The method according to claim 1 , wherein the first temperature is from about 115° C. to about 145° C. and the second temperature is from about 90° C. to about 120° C.

6. The method according to claim 1 , wherein the solvent is selected from the group consisting of N,N-Dimethyl acetamide, N-methyl-2-pyrrolidinone, and combinations thereof.

7. The method according to claim 1 , wherein the salt is selected from the group consisting of lithium halides, sodium halides, potassium halides, and combinations thereof.

8. A microsphere comprising:
a shell comprising a first biodegradable polymer encapsulating at least one second microsphere, the at least one second microsphere comprising a second biodegradable polymer and at least one visualization agent.

9. The microsphere according to claim 8 , wherein the first biodegradable polymer and the second biodegradable polymer are different and at least one of the first biodegradable polymer or the second biodegradable polymer is modified cellulose.

10. The microsphere according to claim 8 , wherein at least one of the first biodegradable polymer or the second biodegradable polymer is an aliphatic polyester.

11. The microsphere according to claim 10 , wherein the aliphatic polyester is selected from the group consisting of polylactide, polylactide-co-glycolide, polylactide-polycaprolactone, and combinations thereof.

12. The microsphere according to claim 8 , further comprising at least one additional visualization agent different from the at least one visualization agent of the at least one second microsphere.

13. The microsphere according to claim 12 , further comprising at least one first bioactive agent, wherein the at least one second microsphere comprises at least one second bioactive agent, the at least one first bioactive agent and the at least one second bioactive agent are different.

14. The microsphere according to claim 8 , wherein the first biodegradable polymer encapsulates at least one third microsphere, the at least one third microsphere comprising at least one additional visualization agent different from the at least one visualization agent of the at least one second microsphere.

15. The microsphere according to claim 14 , wherein the at least one second microsphere comprises at least one first bioactive agent and the at least one third microsphere comprises at least one second bioactive agent, the at least one first bioactive agent and the at least one second bioactive agent are different.

16. The microsphere according to claim 8 , further comprising at least one first bioactive agent, wherein the at least one second microsphere comprises a second shell encapsulating at least one third microsphere comprising a third biodegradable polymer and at least one second bioactive agent.

17. The method according to claim 1 , wherein the plurality of microspheres include oxidized cellulose having a degree of oxidation from about 80% to about 120% of a degree of oxidation of the oxidized cellulose prior to dissolution.

18. The method according to claim 1 , wherein the plurality of microspheres include oxidized cellulose having a molecular weight from about 80% to about 120% of the molecular weight of the oxidized cellulose prior to dissolution.

19. The method according to claim 1 , further comprising encapsulating one or more of the plurality of microspheres within a shell.

20. The method according to claim 1 , wherein the at least one visualization agent is selected from the group consisting of dyes, fluorescent compounds, x-ray contrast agents, ultrasonic contrast agents, MRI contrast agents, CT scan contrast agents, radionucleotides, magnetic materials, and combinations thereof.

Assignees

• Covidien Lp

Inventors

• Ohri Rachit
• Blaskovich Phillip D
• Cherniavsky Olga

Classifications

• A61K49/1818

  particles, e.g. uncoated or non-functionalised microparticles or nanoparticles · CPC title

• A61K9/5042

  Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose · CPC title

• A61K31/714

  Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12 · CPC title

• A61K9/5031

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide) · CPC title

• A61K31/445

  Non condensed piperidines, e.g. piperocaine · CPC title