Poly(amino acid) adhesive tissue grafts

• US 5,733,868 A
• Filed: 04/16/1996
• Issued: 03/31/1998
• Est. Priority Date: 04/16/1996
• Status: Expired due to Fees

• Current Assignee: DePuy Orthopaedics Incorporated (Johnson & Johnson)
• Original Assignee: DePuy Orthopaedics Incorporated (Johnson & Johnson)
• Inventors: Stupp, Samuel I., Peterson, Dale R.
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US08/633,118
• Time in Patent Office: 714 Days
• Field of Search: 514/2, 156/328, 156/336, 524/20
• US Class Current: 514/9.4
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 24/106 Fibrin; Fibrinogen
• 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

A composition and method for repairing damaged connective tissue is provided. The composition comprises pseudo-poly(amino acids) and/or classic poly(amino acids) that exhibit adhesiveness for connective tissues. The composition is formed into an adhesive tissue repair implant and pressed against the damaged tissue to adhere the adhesive composition to the tissue.

Claims

1. A pressure-sensitive adhesive composition comprising

two different poly(amino acids), each of the formula H₂ N--Q--COOR₂ wherein Q is a divalent residue of a polypeptide formed from 1 to 3 species of amino acids, R₂ is H, a metal cation, or ammonium and wherein the amino acid components of Q are represented by the formula aX+bY+cZ wherein a, b, and c represent the respective mole fractions of the amino acids X, Y, and Z;

a=0 to 1, b=0 to 1, and c<

1; and

a+b+c=1.0, and wherein X is selected from glutamate, asparagine, aspartate, and glutamine, Y is selected from lysine and arginine, and Z is an amino acid selected from cysteine, methionine, serine, threonine, glycine, alanine, valine, leucine, and isoleucine, and

wherein the composition exhibits an adhesiveness of about 600 to about 150,000 Pa.

2. The composition of claim 1, wherein the composition is moldable at about 4°

C. to about 60°

C.

3. The composition of claim 1, further comprising a monomer selected from the group consisting of glutamate, aspartate, lysine, and histidine and arginine.

4. The composition of claim 1, wherein the polypeptide bears a negative charge at about physiological pH and further comprising an amino acid monomer with two or more positive charges.

5. The composition of claim 4, wherein the monomer is selected from the group consisting of lysine, arginine, or histidine.

6. The composition of claim 1, wherein the polypeptide bears a positive charge at about physiological pH and further comprising an amino acid monomer with two or more negative charges.

7. The composition of claim 6, wherein the monomer is selected from the group consisting of aspartate or glutamate.

8. The composition of claim 1, further comprising a bioactive agent.

9. A pressure-sensitive adhesive composition comprising

(1) a poly(amino acid) of the formula H₂ N--Q--COOR₂ wherein Q is a divalent residue of a polypeptide formed from 1 to 3 species of amino acids, R₂ is H, a metal cation, or ammonium and wherein the amino acid components of Q are represented by the formula aX+bY+cZ wherein a, b, and c represent the respective mole fractions of the amino acids X, Y, and Z;

a=0 to 1, b=0 to 1, and c<

1; and

a+b+c=1.0;

(a) wherein X is selected from glutamate, asparagine, aspartate, and glutamine;

(b) Y is selected from lysine and arginine; and

(c) Z is an amino acid selected from cysteine, methionine, serine, threonine, glycine, alanine, valine, leucine, and isoleucine;

(2) a monomer selected from the group consisting of glutamate, asparagine, aspartate, glutamine, lysine, arginine, and histidine; and

(3) wherein the composition exhibits on adhesiveness of about 600 to about 150,000 Pa.

10. The composition of claim 9, wherein the polypeptide bears a positive charge at about physiological pH and the monomer is selected from the group consisting of aspartate and glutamate.

11. The composition of claim 9, wherein the polypeptide bears a negative charge at about physiological pH and the monomer is selected from the group consisting of lysine, arginine, and histidine.

12. A method for repairing damaged connective tissue, the method comprising the steps of

(1) selecting a pressure-sensitive adhesive composition comprising a pseudo-poly(amino acid), or a poly(amino acid) of the formula H₂ N--Q--COOR₂ wherein Q is a divalent residue of a polypeptide formed from 1 to 3 species of amino acids, R₂ is H, a metal cation, or ammonium and wherein the amino acid components of Q are represented by the formula aX+bY+cZ, wherein a, b, and c represent the respective mole fractions by the amino acids X, Y, and Z, a+b is >

0, and a+b+c=1.0;

(a) wherein X is selected from glutamate, asparagine, aspartate, or glutamine;

(b) wherein if X is only aspartate, b>

0;

(c) wherein Y is selected from lysine or arginine; and

(d) wherein Z is selected from cysteine, methionine, serine, threonine, glycine, alanine, valine, leucine, isoleucine;

(2) forming an adhesive tissue repair implant from the selected pressure-sensitive adhesive composition; and

(3) pressing the tissue repair implant against the damaged tissue to adhere the adhesive composition to the tissue.

13. A method for effecting repair of damaged connective tissue, the method comprising the steps of

(1) selecting a pressure-sensitive adhesive composition comprising

(a) a poly(amino acid) of the formula H₂ N--Q--COOR₂ wherein Q is a divalent residue of a polypeptide formed from 1 to 3 species of amino acids, R₂ is H, a metal cation, or ammonium and wherein the amino acid components of Q are represented by the formula aX+bY+cZ wherein a, b, and c represent the respective mole fractions of the amino acids X, Y, and Z;

a=0 to 1, b=0 to 1;

c<

1; and

a+b+c=1.0;

(i) wherein X is selected from glutamate, asparagine, aspartate, and glutamine;

(ii) Y is selected from lysine and arginine; and

(iii) Z is an amino acid selected from cysteine, methionine, serine, threonine, glycine, alanine, valine, leucine, and isoleucine; and

(b) a monomer selected from the group consisting of glutamate, aspartate, lysine, histidine, and arginine;

(2) forming an adhesive tissue repair implant from the selected pressure-sensitive adhesive composition; and

(3) pressing the tissue repair implant against the damaged tissue to adhere the adhesive composition to the tissue.

14. A method for effecting repair of damaged connective tissue, the method comprising the steps of

(1) selecting a pressure-sensitive adhesive composition comprising two different poly(amino acids), each of the formula H₂ N--Q--COOR₂ wherein Q is a divalent residue of a polypeptide formed from 1 to 3 species of amino acids, R₂ is H, a metal cation, or ammonium and wherein the amino acid components of Q are represented by the formula aX+bY+cZ wherein a, b, and c represent the respective mole fractions of the amino acids X, Y, and Z;

a=0 to 1, b=0 to 1, and c<

1; and

a+b+c=1.0;

(a) wherein X is selected from glutamate, asparagine, aspartate, and glutamine;

(b) Y is selected from lysine and arginine; and

(c) Z is an amino acid selected from cysteine, methionine, serine, threonine, glycine, alanine, valine, leucine, and isoleucine;

(2) forming an adhesive tissue repair implant from the selected pressure-sensitive adhesive composition; and

(3) pressing the tissue repair implant against the damaged tissue to adhere the adhesive composition to the tissue.

15. The method of claim 14, wherein the forming step comprises the step of maintaining the temperature of the adhesive composition at about 4°

C. to about 60°

C.