| United States Patent | 5,817,303 |
| Stedronsky, et. al. | Oct. 6, 1998 |
Proteinaceous polymers having repetitive units from naturally occurring structural proteins are employed as backbones for functionalities for crosslinking to provide strongly adherent tissue adhesives and sealants. Particularly, block copolymers having repeating units of elastin and fibroin are employed having lysine substitutions in spaced apart units, where the amino group can be crosslinked using difunctional crosslinking agents. The protein polymer contains at least 40 weight percent of repetitive units of 3 to 15 amino acids of at least one naturally occurring protein and in at least two units an amino acid is substituted by an amino acid containing a functional group capable of reacting with a crosslinking agent to form a strongly adherent adhesive composition for bonding together separated tissue or for sealing tissue defects. A preferred adhesive composition contains glutaraldehyde or polymethylene diisocyanate and a protein block copolymer of at least 30 kD containing at least 70 weight percent of repetitive units of Gly-Ala-Gly-Ala-Gly-Ser and Gly-Val-Gly-Val-Pro, where in at least two units an amino acid is substituted with lysine and the copolymer has a lysine equivalent weight in the range of 1 to 20 kD. The protein polymer is produced by recombinant DNA technology, and a kit can be formed containing the crosslinking agent and protein polymer.
| Inventors: | Stedronsky; Erwin R. (San Clement, CA); Cappello; Joseph (San Diego, CA). |
| Assignee: | Protein Polymer Technologies, Inc. (San Diego, CA). |
| Appl. No.: | 435,641 |
| Filed: | May 5, 1995 |
| Intl. Cl. : | A61K 31/785, A01N 37/18, C07K 1/00, C12N 11/00 |
| Current U.S. Cl.: | 424/78.02; 106/124.1; 424/78.06; 435/174; 514/2; 530/350; 530/402; 530/810 |
| Field of Search: | 435/174, 180; 424/486, 78.02; 514/2; 106/124, 124.1; 530/300, 350, 402, 810 |
| 4,187,852 | Feb., 1980 | Urry | 128/334.R |
| 4,589,882 | May, 1986 | Urry | 623/11 |
| 4,898,926 | Feb., 1990 | Urry | 528/328 |
| 5,064,430 | Nov., 1991 | Urry | 623/1 |
| 5,243,038 | Sept., 1993 | Ferrari et al. | 536/23.1 |
| 5,292,362 | Mar., 1994 | Bass et al. | 106/124 |
| 5,336,256 | Aug., 1994 | Urry | 623/1 |
| 5,374,431 | Dec., 1994 | Pang et al. | 424/486 |
| 5,496,712 | Mar., 1996 | Cappello et al. | 435/69.1 |
| 5,514,581 | May, 1996 | Ferrari et al. | 435/252.33 |
| 4334396 | Nov., 1992 | JP | |
| 93/04711 | Mar., 1993 | WO | |
| 94/01508 | Feb., 1994 | WO | |
| 95/05396 | Feb., 1995 | WO |
Kaleem et al., "Collagen-Based Bioadhesive Varnacle Cement Mimic",
Die Angewandte Makromolekulare Chemie (1987), 155:31-43.
Primary Examiner: Naff; David M.
Attorney, Agent or Firm: Trecartin; Richard F., Kresnak; Mark
T. Flehr Hohbach Test Albritton and Herbert
