Polysaccharide based hydrogels

• US 9,700,650 B2
• Filed: 11/05/2010
• Issued: 07/11/2017
• Est. Priority Date: 11/09/2009
• Status: Active Grant

• Current Assignee: Spotlight Technology Partners LLC
• Original Assignee: Spotlight Technology Partners LLC
• Inventors: Gong, Glen, Pai, Suresh Subraya, Sershen, Scott Robert
• Primary Examiner(s): McDonald, Jennifer
• Assistant Examiner(s): Xu, Qing
• Application Number:
  US13/505,683
• Publication Number:
  US 20130045182A1
• Time in Patent Office: 2,440 Days
• 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 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/6903 the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 2400/04 Materials for stopping bleeding
• CPC Class Codes: A61L 26/0052 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 26/008 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C08J 2300/105 containing carboxyl groups
• CPC Class Codes: C08J 2371/02 Polyalkylene oxides
• CPC Class Codes: C08J 2400/106 containing nitrogen atoms
• CPC Class Codes: C08J 2405/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08J 2471/02 Polyalkylene oxides
• CPC Class Codes: C08J 3/075 : Macromolecular gels
• CPC Class Codes: C08J 3/246 : Intercrosslinking of at least two polymers

Abstract

Polysaccharide based hydrogel compositions and methods of making and using the same are provided. The subject polysaccharide based hydrogel compositions are prepared by combining a polysaccharide component with a hydrophilic polymer and a cross-linking agent. Also provided are kits and systems for use in preparing the subject compositions.

Claims

1. A hydrogel composition, comprising

carboxymethylchitosan having a molecular weight of less than or equal to 5,000 Dalton, a degree of deacetylation of 70% to 99%, an electrophilic group, and at least two nucleophilic groups, wherein carboxymethylchitosan is soluble in an aqueous solution;

a multifunctional, multi-armed polyethylene glycol polymer of a molecular weight of 5,000 Dalton to 30,000 Dalton, and comprising at least two nucleophilic groups; and

a multifunctional, multi-armed crosslinker of polyethylene glycol having a molecular weight of 5,000 Dalton to 30,000 Dalton, and comprising at least two electrophilic groups;

wherein the multifunctional, multi-armed polyethylene glycol polymer comprises ester groups to provide for degradation via hydrolysis and

wherein the hydrogel composition comprises;

a covalent bond between carboxymethylchitosan and the multifunctional multi-armed polyethylene glycol polymer;

a covalent bond between carboxymethylchitosan and the multifunctional multi-armed crosslinker and

a covalent bond between the multifunctional multi-armed polyethylene glycol polymer and the multifunctional multi-armed crosslinker.

2. The composition of claim 1, wherein carboxymethylchitosan is present in the composition from 0.5% to 10% by mass.

3. The composition of claim 1, further comprising one or more of a thickening agent, filler, a foaming agent, a biologically active agent, a pharmaceutically active agent, a visualization agent, or a radiopaque agent.

4. The composition of claim 3, wherein the composition comprises a biologically active agent.

5. The composition of claim 4, wherein the biologically active agent is a plasma protein, hormone, enzyme, antiseptic agent, antibiotic, antineoplastic agent, antifungal agent, antiviral agent, anti-inflammatory agent, human or non-human growth factor, anesthetic, cell suspension, cytotoxins, cell proliferation inhibitors, fibrin, fibrinogen, collagen or biomimetic.

6. The composition of claim 3, wherein the composition comprises a filler selected from the group consisting of hydroxyapatite, fibrous silk, carbon fiber, bone chips and a mesh of polyglycolic acid.

7. The composition of claim 3, wherein the composition comprises a visualization agent.

8. The composition of claim 3, wherein the composition comprises a radiopaque agent.

9. A hydrogel composition, comprising:

dicarboxyl chitosan having a molecular weight of less than or equal to 5,000 Dalton, a degree of deacetylation of 70% to 99%, an electrophilic group, and at least two nucleophilic groups, wherein the dicarboxyl chitosan is soluble in an aqueous solution;

a multifunctional, multi-armed polyethylene glycol polymer of a molecular weight of 5,000 Dalton to 30,000 Dalton, and comprising at least two nucleophilic groups; and

a multifunctional, multi-armed crosslinker of polyethylene glycol having a molecular weight of 5,000 Dalton to 30,000 Dalton, and comprising at least two electrophilic groups;

wherein the multifunctional, multi-armed polyethylene glycol polymer comprises ester groups to provide for degradation via hydrolysis and

wherein the hydrogel composition comprises;

a covalent bond between dicarboxyl chitosan and the multifunctional multi-armed polyethylene glycol polymer;

a covalent bond between dicarboxyl chitosan and the multifunctional multi-armed crosslinker and

a covalent bond between the multifunctional multi-armed polyethylene glycol polymer and the multifunctional multi-armed crosslinker.

10. The composition of claim 9, wherein dicarboxyl chitosan is present in the composition from 0.5% to 10% by mass.

11. The composition of claim 9, further comprising one or more of a thickening agent, filler, a foaming agent, a biologically active agent, a pharmaceutically active agent, a visualization agent, or a radiopaque agent.

12. The composition of claim 11, wherein the composition comprises a biologically active agent.

13. The composition of claim 12, wherein the biologically active agent is a plasma protein, hormone, enzyme, antiseptic agent, antibiotic, antineoplastic agent, antifungal agent, antiviral agent, anti-inflammatory agent, human or non-human growth factor, anesthetic, cell suspension, cytotoxins, cell proliferation inhibitors, fibrin, fibrinogen, collagen or biomimetic.

14. The composition of claim 11, wherein the composition comprises a filler selected from the group consisting of hydroxyapatite, fibrous silk, carbon fiber, bone chips and a mesh of polyglycolic acid.

15. The composition of claim 11, wherein the composition comprises a visualization agent.

16. The composition of claim 11, wherein the composition comprises a radiopaque agent.