Injectable non-aqueous compositions and methods of treating vascular disease

• US 9,801,812 B1
• Filed: 05/23/2017
• Issued: 10/31/2017
• Est. Priority Date: 12/04/2015
• Status: Active Grant

• Current Assignee: Covidien LP (Medtronic Plc)
• Original Assignee: Covidien LP (Medtronic Plc)
• Inventors: Girdhar, Gaurav, Ma, Xiaodong, Makridakis, Jennifer
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): MERCIER, MELISSA S
• Application Number:
  US15/602,940
• Publication Number:
  US 20170296466A1
• Time in Patent Office: 161 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• CPC Class Codes: A61K 31/734 Alginic acid
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• 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 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L

Abstract

An injectable non-aqueous composition and a method of treating a vascular disease, the non-aqueous composition including: chitosan having a particle size of no greater than 50 μm; alginate having a particle size of no greater than 50 μm; and a non-aqueous carrier; wherein upon combination and injection into the vascular system of a subject, the composition causes a diseased portion of the vascular system to be absorbed into surrounding tissue.

Claims

1. A method of treating a vascular disease, the method comprising:

providing a non-aqueous composition comprising;

a chitosan having a particle size of no greater than 50 μ

m;

an alginate having a particle size of no greater than 50 μ

m; and

a non-aqueous carrier; and

injecting the non-aqueous composition into a diseased portion of a vascular system of a subject to cause the diseased portion to be absorbed into surrounding tissue.

2. The method of claim 1 wherein the diseased portion comprises an aneurysm.

3. The method of claim 1 wherein injecting the non-aqueous composition comprises forming an embolism in the diseased portion.

4. The method of claim 3 wherein the diseased portion comprises an aneurysm.

5. The method of claim 3 wherein the embolism comprises a chitosan-alginate polyelectrolyte gel.

6. The method of claim 1 wherein the non-aqueous composition further comprises a gel tuning agent.

7. The method of claim 6 wherein the gel tuning agent comprises a crosslinker, a gelling agent, a plasticizer, a binder, or a combination thereof.

8. The method of claim 6 wherein the gel tuning agent comprises a crosslinker selected from the group of an aldehyde, a phosphate, an epoxide, an isocyanate, a natural crosslinker, an NHS-functionalized polyether, a salt, and a combination thereof.

9. The method of claim 6 wherein the gel tuning agent comprises a gelling agent selected from the group of a polyol, a polysaccharide, a polar aprotic solvent, an oil, and a combination thereof.

10. The method of claim 6 wherein the gel tuning agent comprises a plasticizer selected from the group of an alkyl citrate, an adipate, a triglyceride, and a combination thereof.

11. The method of claim 6 wherein the gel tuning agent comprises a binder.

12. The method of claim 1 wherein the non-aqueous carrier comprises a polyether, an ester, a glycerolipid, or a combination thereof.

13. The method of claim 1 wherein the non-aqueous composition is a two-part composition, wherein the chitosan and alginate are in separate parts.

14. The method of claim 1 wherein the chitosan and alginate are each present in the composition in an amount of 1-5 wt-%.

15. A method of treating a vascular disease, the method comprising:

providing a non-aqueous composition comprising;

a chitosan having a particle size of no greater than 50 μ

m;

an alginate having a particle size of no greater than 50 μ

m; and

a non-aqueous carrier; and

injecting the non-aqueous composition into a diseased portion of a vascular system of a subject to form in situ a chitosan-alginate polyelectrolyte gel.

16. The method of claim 15 wherein the diseased portion comprises an aneurysm.

17. The method of claim 15 wherein injecting the non-aqueous composition comprises forming an embolism in the diseased portion.

18. The method of claim 17 wherein the diseased portion comprises an aneurysm.

19. The method of claim 15 wherein the non-aqueous composition further comprises a gel tuning agent.

20. The method of claim 19 wherein the gel tuning agent comprises a crosslinker, a gelling agent, a plasticizer, a binder, or a combination thereof.