Composite polymeric material for biological and medical applications and the method for its preparation

• US 4,427,808 A
• Filed: 07/15/1981
• Issued: 01/24/1984
• Est. Priority Date: 07/21/1980
• Status: Expired due to Fees

• Current Assignee: Ceskoslovenska akademie ved
• Original Assignee: Ceskoslovenska akademie ved
• Inventors: Kalal, Jaroslav, Cefelin, Pavel, Adam, Milan, Tolar, Miroslav, Stol, Miroslav
• Primary Examiner(s): Kight, III, John
• Assistant Examiner(s): Nutter, Nathan M.
• Application Number:
  US06/283,424
• Time in Patent Office: 923 Days
• Field of Search: 523/105, 523/106, 523/113, 523/114, 524/21, 524/24, 524/498, 524/460, 524/845, 525/54.1, 525/937, 351/160 H, 260/123.7
• US Class Current: 524/24
• CPC Class Codes: A61L 15/225 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 33/08 Homopolymers or copolymers of acrylic acid esters
• CPC Class Codes: C08L 89/04 Products derived from waste materials, e.g. horn, hoof or hair
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: Y10S 128/08 Collagen
• CPC Class Codes: Y10S 525/937 Utility as body contact e.g. implant, contact lens or I.U.D.

Abstract

The invention relates to a composite polymeric material suitable for biological and medical applications and to the method for preparation thereof. The composite material consists of 1-99 wt. % of hydrophilic polymer or copolymer based on methacrylic or acrylic esters, 1-99 wt. % of fibrillar collagen, and up to 2.5 wt. % of a crosslinking agent, based on both polymeric components. The composite material may further comprise biologically active compounds and other auxiliary materials, as fillers and/or plasticizers. The composite material is prepared by dispersing the fibrillar collagen in a solution or a highly swollen dispersion of the synthetic hydrophilic polymer or copolymer in a lyotropic agent and the subsequent removal of the lyotropic agent, thus forming a matrix of the synthetic polymer or copolymer penetrated by fibrillar collagen or vice versa. The composite material may be applied on a solid support or reinforced with glass, plastics, cellulose, or metallic materials.

A method for the preparation of the composite material consists in dispersing of fibrillar collagen in a solution or a highly swollen dispersion of the synthetic hydrophilic polymer or copolymer in a lyotropic agent, e.g. in water diluted carboxylic acids, strongly acidified aqueous mixtures of ethanol and methanol, high-concentrated aqueous solutions of lyotropic salts, and high-concentrated aqueous solutions of urea or guanidinium chloride, at temperature not exceeding 37° C., and the subsequent removing of the lyotropic agent from the viscous dispersion at temperature not exceeding 37° C. using the known methods.

The crosslinking agent, e.g. trimethylolurea, formaldehyde, acetaldehyde, glutaraldehyde, starch dialdehyde, glyoxal, or Cr(III) salts, may be added in the course of preparation of the dispersion or after removal of the lyotropic agent.

Claims

1. A method for the preparation of a composite polymeric material for biological and medical applications, wherein fibrillar collagen is dispersed in a solution or a high-swollen dispersion of the synthetic hydrophilic polymer or copolymer in a lyotropic agent selected from the group comprising carboxylic acids diluted with water, strongly acidified aqueous mixtures of ethanol and methanol, high-concentrated aqueous solutions of lyotropic salts, and high-concentrated aqueous solutions of urea or guanidinium chloride, under stirring at temperature not exceeding 37°

C. and then the lyotropic agent is removed from the viscous dispersion at temperature not exceeding 37°

C.

2. The method according to claim 1, wherein a crosslinking agent selected from the group comprising trimethylolurea, formaldehyde, acetaldehyde, glutaraldehyde, starch dialdehyde, glyoxal, and chromium(III) salts, is added, during the preparation of dispersion or after the lyotropic agent has been removed, in the amount of 2.5 weight percent at utmost, related to the total amount of the synthetic polymer or copolymer and collagen.

3. The method according to claim 2, wherein a biologically active compound, and if it is desired, a filler and/or a plasticizer are added during the preparation of dispersion or after the lyotropic agent has been removed.