Non-antigenic collagen and articles of manufacture

• US 4,233,360 A
• Filed: 09/25/1978
• Issued: 11/11/1980
• Est. Priority Date: 10/22/1975
• Status: Expired due to Term

• Current Assignee: Cohesion Technologies Inc. (Angiotech Pharmaceuticals Incorporated)
• Original Assignee: Collagen Corp. (Abbvie Incorporated)
• Inventors: Luck, Edward E., Daniels, John R.
• Primary Examiner(s): Goolkasian, John T.
• Assistant Examiner(s): Dawson, Robert A.
• Application Number:
  US05/945,723
• Time in Patent Office: 778 Days
• Field of Search: 128/156, 128/334 R, 128/DIG. 8, 128/335, 156/78, 156/306, 260/123.7, 424/28, 424/177, 106/141, 106/155, 106/161, 264/202, 427/180, 427/244, 427/372, 427/389, 428/310, 428/316, 428/317, 428/332, 428/478.2
• US Class Current: 424/443
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 15/325 Collagen
• CPC Class Codes: A61L 17/08 of animal origin, e.g. catgut, collagen
• CPC Class Codes: A61L 26/0033 Collagen
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin
• CPC Class Codes: Y10S 128/08 Collagen
• CPC Class Codes: Y10S 623/915 Method or apparatus for preparing biological material
• CPC Class Codes: Y10T 428/249986 Void-containing component contains also a solid fiber or solid particle
• CPC Class Codes: Y10T 428/249988 Of about the same composition as, and adjacent to, the void-containing component
• CPC Class Codes: Y10T 428/26 Web or sheet containing structurally defined element or component, the element or component having a specified physical dimension
• CPC Class Codes: Y10T 428/31768 Natural source-type polyamide [e.g., casein, gelatin, etc.]

Abstract

Collagen, available from domestic animals, is freed of noncollagen proteins, glycosaminoglycans and lipids by enzymatic treatment with a proteolytic enzyme to yield a product which is soluble in dilute acidic aqueous solutions (collagen in solution--CIS). The naturally occurring collagen is modified by removal of certain terminal peptide chains, which are described as telopeptides. The modified collagen, so derived, is described as atelopeptide collagen. Native collagen is immunogenic, while atelopeptide collagen is nonimmunogenic or possessed of a negligibly low level of immunogenicity.

The collagen in solution is then treated according to a specific regimen under conditions whereby the collagen slowly separates from solution while exposed to mild shear forces. This procedure results in the formation of a fibrous precipitate composed of regularly ordered fibers of collagen possessed of a ropelike structure. These resulting aggregates are referred to as native fibrous micropolymers (NFM). Once the regimen or procedure is completed, and the fiber mass has been formed, the fibrous micropolymers may be freed of salt, taken up in a different solution or modified. For example, cross-links may then be introduced to stabilize the fibers. The products find wide use as packing, membranes, fibers, bags, supports, integuments, and are especially suitable for biologic implantation or application.

Claims

1. A method for preparing an atelopeptide collagen burn dressing comprising a laminate of a foam and a film which comprises:

lyophilizing a dispersion of fibers of atelopeptide collagen to form a foam;

cross-linking said foam;

applying an aqueous dispersion of a mixture of cross-linked and non-cross-linked atelopeptide collagen to said foam to form a laminate; and

dehydrating said laminate, wherein said dispersion of fibers of atelopeptide collagen is prepared by inducing slow desolubilization of atelopeptide collagen from an aqueous solution of atelopeptide collagen while subjecting said solution to mild shear force, whereby fibers of atelopeptide collagen are formed having a mean diameter of at least about 500 nm and appearing as a rope-like structure in a scanning electron micrograph.

2. A method according to claim 1, wherein said cross-linking comprises treating said atelopeptide collagen with formaldehyde.

3. A method according to claim 1, wherein said slow desolubilization results from an initial acidic medium to which is slowly added an inorganic alkaline salt.

4. A method according to claim 1, wherein said dispersion of fibers of atelopeptide collagen is prepared by containing said aqueous solution in a dialysis bag which is slowly rotated in an aqueous inorganic alkaline salt medium.

5. A burn dressing prepared according to any of claims 1 to 4.