Adhesives derived from bioadhesive polyphenolic proteins

• US 5,015,677 A
• Filed: 06/27/1988
• Issued: 05/14/1991
• Est. Priority Date: 04/25/1986
• Status: Expired due to Term

• Current Assignee: AL Marzook United Commercial Co.
• Original Assignee: Bio-Polymers Incorporated
• Inventors: Picciano, Paul T., Benedict, Christine V.
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US07/213,439
• Time in Patent Office: 1,051 Days
• Field of Search: 524/17, 524/21, 524/22, 524/25, 530/328, 530/350, 106/124, 106/125, 106/126, 106/127, 106/128, 106/129, 106/130, 106/133, 106/138, 106/139, 106/140, 106/, 106/141, 106/149, 106/150, 106/157, 106/158, 156/326, 156/336
• US Class Current: 524/17
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 24/106 Fibrin; Fibrinogen
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: C09J 189/00 Adhesives based on proteins; Adhesives based on derivatives thereof

Abstract

An adhesive or coating formulation useful in biomedical application and particularly well suited for use in aqueous environments is provided comprising:

(1) a bioadhesive polyphenolic protein component having from about 5 to about 99 weight percent of a proteinaceous substance comprising from about 10 to about 400 of the following repeating decapeptide unit: ##STR1## in which each X is hydrogen or hydroxyl and each R is hydrogen or methyl; (2) from about 1.0 to about 40 weight percent of a cross-linking agent which promotes cross-linking of the decapeptide;

(3) one or more additives which promote the desired properties of the formulation, said additives comprising at least one surfactant and being present in an amount of from 0% to about 90% by weight, and

(4) a filler compatible with the intended use of the formulation, said filler being present in an amount of from 0% to about 50% by weight.

Claims

1. A water-imperious adhesive or coating formulation exhibiting an adhesive strength of at least about 100 gm/cm² when used on soft tissue comprising:

(1) a bioadhesive polyphenolic protein component having from about 5 to about 99 weight percent of a proteinaceous substance comprising from about 50 to about 150 of the following repeating decapeptide unit;

##STR4## in which each X is hydrogen or hydroxyl, and each R is hydrogen or methyl;

(2) from about 1.0 to about 40 weight percent of a cross-linking agent which promotes cross-linking of the decapeptide;

(3) one or more additives which promote the desired properties of the formulation, said additives comprising at least one surfactant and being present in an amount of from 0% to about 90% by weight, and

(4) a filler compatible with the intended use of the formulation, said filler being present in an amount of from 0% to about 50% by weight,

wherein the bioadhesive polyphenolic protein component (1) is derived from the marine mussel.

2. A water-impervious coating formulation according to claim 1 wherein said proteinaceous substance comprises from about 50 to about 150 of said decapeptide unit.

3. A water-impervious adhesive according to claim 1 wherein said adhesive strength is at least about 150 gm/cm ².

4. A water-impervious adhesive or coating formulation according to claim 1 in which the bioadhesive polyphenolic protein component and the cross-linking agent together are present in an amount ranging from about 25 to about 90 weight percent of the formulation.

5. A water-impervious coating formulation according to claim 2 for use in an underwater environment in which:

(a) the bioadhesive polyphenolic protein component and the cross-linking agent are together present in an amount ranging from about 50 to about 80 weight percent; and

(b) a surfactant functioning as a spreading agent in an amount ranging from about 20 to about 40 weight percent of the formulation.

6. A water-impervious formulation according to claim 5 in which the surfactant is sodium dodecylsulfate or sodium dodecylbenzenesulfonate.

7. A water-impervious adhesive formulation according to claim 1 for biomedical use in which each additive and filler is compatible with the organs to which the formulation is applied.

8. A biomedical adhesive formulation according to claim 7 for use in orthopedic repair, reconstruction or prosthetics, in which;

(a) the bioadhesive polyphenolic component and the cross-linking agent are together present in an amount ranging from about 30 to about 70 weight percent;

(b) the filler is present in an amount ranging from about 30 to about 60 weight percent.

9. A biomedical adhesive formulation according to claim 8 in which the filler is selected from the group consisting of collagen, hyaluronic acid, chondroitan sulfate, elastin, laminin, casein, hydroxyapatite, or a similar naturally occurring proteinaceous, inorganic, or mucopolysaccharide substance.

10. A biomedical adhesive formulation according to claim 9 in which the filler is collagen.

11. A biomedical adhesive formulation according to claim 9 in which the cross-linking agent is mushroom tyrosinase.

12. An adhesive formulation according to claim 1 for use in ophthalmic surgery in which the bioadhesive polyphenolic protein component and the cross-linking agent are together present in an amount varying from about 70 to about 100 weight percent.

13. An adhesive formulation according to claim 12 in which the cross-linking agent is mushroom tyrosinase.

14. An adhesive formulation according to claim 12 for sealing ophthalmic incisions and perforations with alloplastic materials in which the bioadhesive polyphenolic protein component and the cross-linking agent are together present in an amount varying from about 3 to about 100 weight percent and a collagen filler is incorporated in amounts ranging from 0 to about 40 weight percent.

15. An adhesive and coating formulation according to claim 1 for bonding plant materials or coating plant surfaces in which each additive and filler is biochemically compatible with the plant to which the formulation is applied.

16. An adhesive formulation according to claim 1 for joining substrates through which an electric current is to be passed, said formulation additionally containing electrically conductive additives in an amount ranging from about 10 to about 80 weight percent.

17. A method for adhering two or more substrates in an underwater environment which comprises applying to the adherent surfaces either under water or prior to submersion in water an adhesive formulation according to claim 1.

18. A method for coating an underwater surface so as to prevent the growth of microbes or plants thereon, or the attachment thereto of marine animals, said method comprising applying to said surface a formulation according to claim 5.

19. A method for preventing corrosion of an underwater surface which comprises applying to said surface a coating formulation according to claim 5.

20. A method of priming a surface for subsequent application of a coating or adhesive which method comprises applying to said surface a formulation according to claim 1.

21. In orthopedic repair and reconstruction, a method for adhering bone, tendon, ligament, meniscus, muscle, each to each other or adhering any of them to alloplastic materials, which method comprises applying to a surface on which adhesion is sought a formulation according to claim 8.

22. A method according to claim 21 in which, in the formulation, the biocompatible filler is collagen.

23. A method according to claim 21 in which, in the formulation, the cross-linking agent is mushroom tyrosinase.

24. In dentistry, a method for adhering retainers, bridges, crowns or filler material to tooth structure, for securing loose teeth and for repairing broken teeth, which method comprises applying to the surface on which adhesion or repair is sought a formulation according to claim 7.

25. A method for attaching donor tissue or alloplastic grafts to promote wound and incision closure and prevent bacterial contamination in soft tissue which comprises applying to the surface to be treated a formulation according to claim 7 and attaching said donor tissue or alloplastic graft thereto.

26. A method for sealing wound or incision closures and the regions adjacent thereto which have been punctured by associated surgical closure devices to substantially reduce fluid seepage therethrough which comprises applying to the site to be sealed a formulation according to claim 7.

27. A method for treating wounds, fractures and dislocations in animals which comprises applying to the surface to be treated a formulation according to claim 7.

28. A method for implanting in a patient a prosthesis or medical device containing drugs, medications, single cells or sheets of cells, or electronic circuitry, which comprises adhering said prosthesis or device to the desired site in the patient with an adhesive formulation according to claim 7.

29. In ophthalmic surgery, a method for repair or attachment of alloplastic or donor tissue which comprises applying to the surfaces to be adhered an adhesive formulation according to claim 12 and attaching said alloplastic or donor tissue thereon.

30. A method for sealing ophthalmic incisions or punctures with alloplastic material which comprises applying to the surface to be treated a formulation according to claim 12 and attaching said alloplastic material thereto.

31. A method for treating plants for the purpose of repairing injury, reconstruction, wound closure, grafting or promoting hybridization or genetic alteration, which comprises applying to surfaces which are to be adhered a formulation according to claim 15.

32. A method for protecting plants against attack from fungal diseases which comprises applying to the surface areas of the plant subject to fungal attack a coating formulation according to claim 15.

33. A method for joining two substrates through which an electric current is to be passed which comprises adhering the substrates to each other with an adhesive formulation according to claim 16.

34. A method for separating heavy metals and contaminants from fluids which comprises applying to a nitrocellulose filter or to resin beads used as support matrices in ultrafiltration procedures and column chromatography, respectively, a coating formulation according to claim 1.