Chitosan-containing protective composition

• US 8,530,632 B2
• Filed: 04/23/2009
• Issued: 09/10/2013
• Est. Priority Date: 04/24/2008
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Xomed Incorporated (Medtronic Plc)
• Inventors: Tijsma, Edze Jan, Gonzalez, Maria Nieves, Myntti, Matthew Franco, Vaccaro, Brian
• Primary Examiner(s): OLSON, ERIC
• Application Number:
  US12/429,150
• Publication Number:
  US 20090291912A1
• Time in Patent Office: 1,601 Days
• Field of Search: None
• US Class Current: 536/20
• CPC Class Codes: A61K 31/717 Celluloses
• CPC Class Codes: A61K 31/718 Starch or degraded starch, e.g. amylose, amylopectin
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• 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 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: C08B 37/003 Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof

Abstract

Body tissue and structures may be protected using a fluid containing a mixture of partially crosslinked polysaccharide and a further crosslinker. The mixture desirably is sprayable, forms a fluid protective layer via in situ crosslinking, desirably does not drip or run from a treatment site, and may avoid the use of more rapidly curing but potentially less bioacceptable crosslinkers at the treatment site.

Claims

1. A two-part composition, the first part comprising a sterilized crosslinked polysaccharide in sealed packaging and the second part comprising a sterilized further crosslinker for the polysaccharide in sealed packaging, wherein the polysaccharide or further crosslinker comprise a biocompatible chitosan, the polysaccharide and further crosslinker are in a molar ratio of about 20:

1 to about 1;

20 and the two parts when hydrated are sprayable fluids deliverable through a spray applicator and reacting with one another to provide a thin, conformal, non-dripping protective layer when sprayed on a body temperature substantially vertical skin surface.

2. A composition according to claim 1 wherein the polysaccharide comprises a chitosan.

3. A composition according to claim 1 wherein the further crosslinker comprises a chitosan.

4. A composition according to claim 3 wherein the polysaccharide and further crosslinker comprise a chitosan derivative or modified chitosan.

5. A composition according to claim 1 wherein the polysaccharide or further crosslinker comprise a cellulose.

6. A composition according to claim 1 wherein the polysaccharide or further crosslinker comprise a starch.

7. A composition according to claim 1 wherein the polysaccharide or further crosslinker comprise chitin, chondroitin sulfate, dextran, glycogen or hyaluronic acid.

8. A composition according to claim 1 wherein the polysaccharide and further crosslinker are in a molar ratio of about 3:

1 to about 1;

5.

9. A composition according to claim 1 further comprising phosphate ions.

10. A composition according to claim 1 packaged in a syringe.

11. A composition according to claim 10 wherein the polysaccharide is in dry particulate form.

12. A composition according to claim 1 wherein the protective layer forms a gel.

14. A composition according to claim 1 wherein the first part is in a first sealed package and the second part is in a second sealed package.

16. A composition according to claim 1 wherein the polysaccharide or further crosslinker comprise a chitosan derivative that is a chitosan salt or contains one or more modified hydroxyl or modified amino groups that alter solubility or mucoadhesion characteristics of the derivative.

17. A composition according to claim 16 wherein the derivative is a thiolated chitosan, carboxymethyl chitosan, acetylated chitosan, alkylated chitosan or sulfonated chitosan.

18. A composition according to claim 16 wherein the derivative is an O-alkyl ether, O-acyl ester, cationized trimethyl chitosan or a chitosan modified with polyethylene glycol.

13. A protective layer, the layer comprising an initially fluid mixture of a crosslinked polysaccharide and a further crosslinker for the polysaccharide, wherein the layer forms a thin, non-dripping film when sprayed on a body temperature substantially vertical skin surface, the polysaccharide or further crosslinker comprise a biocompatible chitosan and the crosslinked polysaccharide is formed from a crosslinker that is different from the further crosslinker.

15. A protective layer according to claim 13 wherein the film is substantially vertical.

19. A protective layer according to claim 13 wherein the polysaccharide and further crosslinker are in a molar ratio of about 20:

1 to about 1;

20.

20. A method for treating body tissue or structure, which method comprises:

a) mixing a two-part composition, the first part comprising a fluid crosslinked polysaccharide solution and the second part comprising a further crosslinker for the polysaccharide, wherein the polysaccharide or further crosslinker comprise a biocompatible chitosan and the polysaccharide and further crosslinker are in a molar ratio of about 20;

1 to about 1;

20; and

b) applying the mixed parts as a fluid directed onto the body tissue or structure to form a protective layer thereon.

21. A method according to claim 20 wherein the polysaccharide or further crosslinker comprises a chitosan derivative or modified chitosan.