Biomaterials and a method for making and using the same

• US 9,855,337 B2
• Filed: 01/31/2008
• Issued: 01/02/2018
• Est. Priority Date: 01/31/2007
• Status: Active Grant

• Current Assignee: Alumend LLC
• Original Assignee: Alumend LLC
• Inventors: Utecht, Ronald E., Kloster, Kaia L., Downey, Therese M., Haberer, Barbara R.
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): CRAIGO, WILLIAM A
• Application Number:
  US12/023,963
• Publication Number:
  US 20080200948A1
• Time in Patent Office: 3,624 Days
• Field of Search: 606214, 156336, 514777, 523105, 530402, 536 552
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• 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 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 24/08 Polysaccharides A61L24/043 takes precedence
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• 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
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

Biomaterials are disclosed having unique properties that make it a useful material in adhesives, local drug delivery applications and as filler or bulking material. The biomaterials are strong, safe and easily used as a surgical adhesive. Treated chitosan, modified chitosan or modified and treated chitosan compositions are disclosed displaying strengths suitable for general surgical applications. The materials can be used as a drug delivery vehicle which allows for the localization of the delivered drug as well as a programmable tether which allows for the release of the drug on a timed basis or in response to a physiological state such as the release of proteolytic enzymes. The materials of this invention can also be modified and treated to optimize the retention of water, thereby serving as a useful filler or bulking material.

Claims

1. A method for treating chitosan comprising:

dissolving a raw chitosan in a first aqueous acid solution for a time and at a temperature sufficient to facilitate complete chitosan dissolution,

adding alkyl sulfonic acid chloride to covalently modify the chitosan,

adding a base to the dissolved chitosan solution to precipitate the chitosan, where the base addition raises a pH of the dissolved chitosan solution to a value from about pH 9 to about pH 10,

re-dissolving the precipitated chitosan in a second aqueous acid solution,

adding a base to the redissolved chitosan solution to precipitate the chitosan, centrifuging the re-precipitated chitosan solution to separate the chitosan from the solution,

dialyzing the re-precipitated chitosan in an acid solution for a time and at a temperature sufficient to dissolve the chitosan in a dialysis tube, and

dialyzing the dialyzed re-precipitated chitosan against a buffered salt solution until a pH of the chitosan solution is from pH 5.7 to pH 6.0.

2. The method of claim 1, further comprising:

freeze drying the dialyzed chitosan.

3. The method of claim 1, further comprising:

adding an additive package to the chitosan.

4. The method of claim 1, wherein the alkyl sulfonic acid chloride is octane sulfonic acid chloride, and wherein the covalently modified chitosan is chitosan covalently modified with octane sulfonic acid.

5. The method of 4, wherein the chitosan is covalently modified with the octane sulfonic acid via a sulfonamide linkage.