Aldehyde-functionalized polysaccharides

• US 8,580,950 B2
• Filed: 12/21/2010
• Issued: 11/12/2013
• Est. Priority Date: 07/02/2009
• Status: Active Grant

• Current Assignee: Actamax Surgical Materials, LLC (DSM-Firmenich AG)
• Original Assignee: Actamax Surgical Materials, LLC (DSM-Firmenich AG)
• Inventors: Lu, Helen S. M., Shuey, Steven W.
• Primary Examiner(s): MAIER, LEIGH C
• Application Number:
  US12/973,967
• Publication Number:
  US 20120142787A1
• Time in Patent Office: 1,057 Days
• Field of Search: None
• US Class Current: 536/112
• CPC Class Codes: C08B 15/02 Oxycellulose; Hydrocellulose; Cellulosehydrate, e.g. microcrystalline cellulose
• CPC Class Codes: C08B 31/18 Oxidised starch
• CPC Class Codes: C08B 37/00 Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof cellulose D21; microbiological processes C12P
• CPC Class Codes: C08B 37/0018 Pullulan, i.e. (alpha-1,4)(alpha-1,6)-D-glucan; Derivatives thereof
• CPC Class Codes: C08B 37/0021 Dextran, i.e. (alpha-1,4)-D-glucan; Derivatives thereof, e.g. Sephadex, i.e. crosslinked dextran
• CPC Class Codes: C08B 37/0054 Inulin, i.e. beta-2,1-D-fructofuranan; Derivatives thereof
• CPC Class Codes: C08B 37/0072 Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
• CPC Class Codes: C08L 1/04 Oxycellulose; Hydrocellulose , e.g. microcrystalline cellulose
• CPC Class Codes: C08L 3/10 Oxidised starch
• CPC Class Codes: C08L 5/00 Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
• CPC Class Codes: C08L 5/02 Dextran; Derivatives thereof
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08L 5/12 Agar or agar-agar , i.e. mixture of agarose and agaropectin; Derivatives thereof

Abstract

Novel aldehyde-functionalized polysaccharide compositions containing pendant dialdehyde groups are described that are more stable in aqueous solution than oxidized polysaccharides. The aldehyde-functionalized polysaccharides may be reacted with various amine-containing polymers to form hydrogel tissue adhesives and sealants that may be useful for medical applications such as wound closure, supplementing or replacing sutures or staples in internal surgical procedures such as intestinal anastomosis and vascular anastomosis, tissue repair, preventing leakage of fluids such as blood, bile, gastrointestinal fluid and cerebrospinal fluid, ophthalmic procedures, drug delivery, and preventing post-surgical adhesions.

Claims

1. A composition comprising at least one aldehyde-functionalized polysaccharide containing pendant dialdehyde groups, said aldehyde-functionalized polysaccharide having a weight-average molecular weight of about 1,000 to about 1,000,000 Daltons and a degree of aldehyde substitution of about 5% to about 100%, wherein:

(i) each pendant dialdehyde group is attached to the polysaccharide through a linking group comprising carbon, hydrogen, and oxygen atoms,

(ii) said linking group is attached to the polysaccharide by an ether or an ester linkage,

(iii) said linking group does not contain an aromatic ring,

(iv) said pendant dialdehyde groups comprise two aldehyde functionalities separated by 2 to 4 atoms, and

(v) said two aldehyde functionalities are not bound to two adjacent carbon atoms that are bound together by a carbon-carbon double bond.

2. The composition according to claim 1 wherein the linking group does not contain a nitrogen atom.

3. The composition according to claim 1 wherein the linking group comprises carbon, hydrogen, oxygen, and nitrogen atoms.

4. The composition according to claim 1 wherein the linking group is attached to the polysaccharide by an ether linkage.

5. The composition according to claim 1 wherein said linking group contains an alkoxy group that is alpha to one aldehyde of the pendant dialdehyde group.

6. The composition according to claim 1 wherein the aldehyde-functionalized polysaccharide is selected from the group consisting of aldehyde-functionalized derivatives of:

dextran, carboxymethyldextran, starch, agar, cellulose, hydroxyethylcellulose, carboxymethylcellulose, pullulan, inulin, levan, and hyaluronic acid.

7. The composition according to claim 6 wherein the aldehyde-functionalized polysaccharide is aldehyde-functionalized dextran.

8. The composition according to claim 6 wherein the aldehyde-functionalized polysaccharide is aldehyde-functionalized inulin.

9. The composition according to claim 1 wherein the weight-average molecular weight is about 7,000 to about 20,000 Daltons.

10. The composition according to claim 1 wherein the composition is in the form of an aqueous solution or dispersion.

11. The composition according to claim 10 wherein the aqueous solution or dispersion contains the aldehyde-functionalized polysaccharide at a concentration of about 5% to about 50% by weight relative to the total weight of the solution or dispersion.

12. The composition according to claim 10 further comprising an aldehyde-functionalized polysaccharide having pendant single aldehyde groups.