Protective gel based on chitosan and oxidized polysaccharide

• US 9,433,636 B2
• Filed: 04/23/2009
• Issued: 09/06/2016
• Est. Priority Date: 04/24/2008
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Tijsma, Edze Jan, Gonzalez, Maria Nieves, TenBroek, Erica M., Schaffhausen, Nancy
• Primary Examiner(s): BERRY, LAYLA D
• Application Number:
  US12/429,141
• Publication Number:
  US 20090270346A1
• Time in Patent Office: 2,693 Days
• Field of Search: None
• US Class Current: 1/1
• 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 31/717 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 9/0043 Nose
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 26/0052 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 26/0066 Medicaments; Biocides
• CPC Class Codes: A61L 26/008 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 26/009 Materials resorbable by the body
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

Bodily tissue and structures may be protected using a fluid layer containing a mixture of chitosan and oxidized polysaccharide. The mixture forms a protective gel layer via in situ crosslinking. Compared to crosslinking using a low molecular weight aldehyde such as glutaraldehyde or genipin, oxidized polysaccharides appear to provide faster gelation while avoiding the use of potentially less bioacceptable low molecular weight aldehydes.

Claims

1. An article of manufacture comprising a crosslinked hydrogel layer reacted from a fluid mixture containing chitosan and oxidized polysaccharide in amounts sufficient to form a protective gel layer in situ, the crosslinked hydrogel layer being in contact with and coating and conforming to the shape of cilia on a ciliated mucosal tissue in an ear, nasal cavity, sinus cavity or throat, the chitosan having a number average molecular weight before sterilization of at least about 50 kDa, and wherein the crosslinked hydrogel layer provides a protective gel layer that remains exposed to air or other nearby gases, reduces adhesions to anatomy, is biodegradable or bioresorbable without shedding large solid chunks and resists detachment or other disruption from such tissue until natural degradation or resorption of the protective gel layer takes place.

2. An article according to claim 1 wherein the crosslinked hydrogel layer is in contact with and coats and conforms to the shape of cilia on a ciliated mucosal nasal cavity tissue.

3. An article according to claim 1 wherein the crosslinked hydrogel layer is in contact with and coats and conforms to the shape of cilia on a ciliated mucosal throat tissue.

4. An article according to claim 1 wherein the chitosan is an unmodified chitosan or a chitosan salt.

5. An article according to claim 1 wherein the chitosan is a chitosan derivative.

6. An article according to claim 1 wherein the oxidized polysaccharide comprises oxidized starch.

7. An article according to claim 1 wherein the oxidized polysaccharide comprises oxidized cellulose.

8. An article according to claim 1 wherein the oxidized polysaccharide comprises oxidized chitin, oxidized chitosan, oxidized chondroitin sulfate, oxidized dextran, oxidized glycogen or oxidized hyaluronic acid.

9. An article according to claim 1 wherein the chitosan and oxidized polysaccharide are combined in a ratio of about 10:

1 to about 1;

20.

10. An article according to claim 1 wherein the chitosan and oxidized polysaccharide are combined in a ratio of about 3:

1 to about 1;

5.

11. An article according to claim 1 further comprising phosphate ions.

12. An article according to claim 1 wherein the chitosan is a low molecular weight material having a number average molecular weight before sterilization of about 50 to about 200 kDa.

13. An article according to claim 1 wherein the chitosan is a medium molecular weight material having a number average molecular weight of about 200 to about 500 kDa.

14. An article according to claim 1 wherein the chitosan is a high molecular weight material having a number average molecular weight greater than about 500 kDa.

15. An article according to claim 1 wherein the protective gel layer remains a gel during biodegradation or bioresorbtion.

16. An article according to claim 1 wherein the fluid mixture is sprayable before formation of the crosslinked hydrogel layer.

17. An article according to claim 1 wherein the protective gel layer has a residence time of one day to four weeks.

18. An article according to claim 1 wherein the protective gel layer includes available chitosan amine hydrogen atoms.

19. An article according to claim 1 wherein the fluid mixture consists essentially of chitosan, oxidized polysaccharide, a solvent selected from water and alcohols, and an optional buffering agent.

20. An article according to claim 1 wherein the crosslinked hydrogel layer is in contact with and coats and conforms to the shape of cilia on a ciliated mucosal sinus cavity tissue.

21. An article according to claim 1 wherein the fluid mixture contains chitosan and oxidized polysaccharide in a combined amount of about 1 to about 10 wt. % of the fluid mixture.