Aldehyde-functionalized polysaccharides

• US 8,580,951 B2
• Filed: 07/01/2010
• 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:
  US12/996,477
• Publication Number:
  US 20120004194A1
• Time in Patent Office: 1,230 Days
• Field of Search: None
• US Class Current: 536/112
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• 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 37/0021 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: 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

Abstract

Novel aldehyde-functionalized polysaccharide compositions are described that are more stable in aqueous solution than oxidized polysaccharides or other types of polysaccharides containing pendant aldehyde groups. 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 aldehyde groups, said aldehyde-functionalized polysaccharide having a weight-average molecular weight of about 3,000 to about 250,000 Daltons and a degree of aldehyde substitution of greater than 40% to about 200%;

wherein;

(i) said pendant aldehyde groups are attached to the polysaccharide through linking groups which do not contain a nitrogen atom;

(ii) said linking groups are attached to the polysaccharide by ether linkages; and

(iii) said linking groups contain an alkoxy group alpha to the pendant aldehyde group.

2. The composition according to claim 1 wherein the degree of aldehyde substitution is 40% to about 120%.

3. 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.

4. The composition according to claim 3 wherein the aldehyde-functionalized polysaccharide is aldehyde-functionalized dextran.

5. The composition according to claim 3 wherein the aldehyde-functionalized polysaccharide is aldehyde-functionalized inulin.

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

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

8. The composition according to claim 7 wherein the aqueous solution or dispersion contains the aldehyde-functionalized polysaccharide at a concentration of about 5% to about 40% by weight relative to the total weight of the solution or dispersion.