Multibranched bioadhesive compounds and synthetic methods therefor

1. A compound comprising the formula (I)

wherein

each L a , L c , L e , L g and L i , independently, is a linker;

each L k and L m , independently, is a linker or a suitable linking group selected from amine, amide, ether, ester, urea, carbonate or urethane linking groups;

each X, X 3 , X 5 , X 7 , X 9 , X 11 , X 13 and X 15 , independently, is an oxygen atom or NR;

R, if present, is H or a branched or unbranched C1-10 alkyl group;

each R 1 , R 3 , R 5 , R 7 , R 9 , R 11 , R 13 and R 15 , independently, is a branched or unbranched C1-C15 alkyl group;

each DHPD xx and DHPD dd , independently, is a multihydroxy phenyl derivative residue;

ee is a value from 1 to about 80;

gg is a value from 0 to about 80:

ii is a value from 0 to about 80;

kk is a value from 0 to about 80;

mm is a value from 0 to about 80;

oo is a value from 1 to about 120;

qq is a value from 1 to about 120;

ss is a value from 1 to about 120;

uu is a value from 1 to about 120; and

vv is a value from 1 to about 80.

2. The compound of claim 1 , wherein L a is a residue of a C1-C15, alkyl anhydride or activated dicarbonyl moiety, a poly(ethyleneglycol) bis(carboxymethyl)ether, polyethylene glycol or an amino acid.

3. The compound of claim 2 , wherein the dicarbonyl moiety is a residue of succinic acid or the amino acid is glycine.

4. The compound of claim 1 , wherein L c is a residue of a C1-C15 alkyl lactone or lactam, a poly C1-C15 alkyl lactone or lactam, a polyester, or a compound comprising the formula Y 4 —R 17 —C(═O)—Y 6 ,

wherein Y 4 is OH, NHR, a halide, or an activated derivative of OH or NHR;

R 17 is a branched or unbranched C1-C15 alkyl group; and

Y 6 is NHR, a halide, or OR.

5. The compound of claim 4 , wherein the polylactone is a polycaprolactone.

6. The compound of claim 1 , wherein L e is a residue of an alkylene diol, an alkylene diamine or a poly(alkylene oxide) polyether or derivative thereof.

7. The compound of claim 6 , wherein L e is a poly(alkylene oxide) or —O—CH 2 CH 2 —O—CH 2 CH 2 —O—.

8. The compound of claim 1 , wherein L g or L c is a residue of a C1-C15 alkyl lactone or lactam, a poly C1-C15 alkyl lactone or lactam, or a compound comprising the formula Y 4 —R 17 —C(═O)—Y 6 ,

wherein Y 4 is OH, NHR, a halide, or an activated derivative of OH or NHR;

R 17 is a branched or unbranched C1-C15 alkyl group; and

Y 6 is NHR, a halide, or OR.

9. The compound of claim 8 , wherein the polylactone is polycaprolactone.

10. The compound of claim 1 , wherein L i is a residue of a C1-C15 alkyl anhydride or activated dicarbonyl moiety, a poly(ethyleneglycol) bis(carboxymethyl)ether or an amino acid.

11. The compound of claim 10 , wherein L i is a residue of succinic acid or glycine.

12. The compound of claim 1 , wherein X, X 7 , X 11 and X 15 are each O or NH.

13. The compound of claim 1 , wherein R 1 , R 7 , R 11 and R 15 are each —CH 2 CH 2 —.

14. The compound of claim 1 , wherein X 3 , X 5 , X 9 and X 13 are each O.

15. The compound of claim 1 , wherein R 3 , R 5 , R 9 and R 13 are each —CH 2 —.

16. The compound of claim 1 , wherein L k and L m form an amide, ester or carbamate.

17. The compound of claim 1 , wherein each DHPD xx and DHPD dd , independently, is a residue of a formula comprising:

wherein Q is an OH;

“z” is 2 to 5;

each X 1 , independently, is H, NH 2 , OH, or COOH;

each Y 1 , independently, is H, NH 2 , OH, or COOH;

each X 2 , independently, is H, NH 2 , OH, or COOH;

each Y 2 , independently, is H, NH 2 , OH, or COOH;

Z is COOH, NH 2 , OH or SH;

aa is a value of 0 to about 4;

bb is a value of 0 to about 4; and

optionally provided that when one of the combinations of X 1 and X 2 , Y 1 and Y 2 , X 1 and Y 2 or Y 1 and X 2 are absent, then a double bond is formed between the C aa and C bb , further provided that aa and bb are each at least 1 to form the double bond when present.

18. The compound of claim 1 , wherein DHPD xx and DHPD dd residues are from 3,4-dihydroxy phenylalanine (DOPA), 3,4-dihydroxyphenethylamine (dopamine), 3,4-dihydroxyhydrocinnamic acid (DOHA), 3,4-dihydroxyphenyl ethanol, 3,4 dihydroxyphenylacetic acid, 3,4 dihydroxyphenylamine, or 3,4-dihydroxybenzoic acid.

19. The compound of claim 1 , wherein

L a is a residue of succinic acid;

L c is a residue of a polycaprolactone, a caprolactone, a polylactic acid, a polylactone or a lactic acid or lactone;

L e is a residue of a polyethylene glycol;

L g is a residue of a polycaprolactone, a caprolactone, a polylactic acid, a polylactone or a lactic acid or lactone;

L i is a residue of succinic anhydride;

X, X 7 , X 11 and X 15 are each O or NH;

R 1 , R 7 , R 11 and R 15 are each —CH 2 CH 2 —;

X 3 , X 5 , X 9 and X 13 are each O;

R 3 , R 5 , R 9 and R 13 are each —CH 2 —;

L k and L m form an amide; and

DHPD xx and DHPD dd are residues from 3,4-dihydroxyhydrocinnamic acid (DOHA).

20. The compound of claim 1 , wherein

L a is a residue of glycine;

L c is a residue of a polycaprolactone, a caprolactone, a polylactic acid, a polylactone or a lactic acid or lactone;

L e is a residue of a polyethylene glycol;

L g is a residue of a polycaprolactone, a caprolactone, a polylactic acid, a polylactone or a lactic acid or lactone;

L i is a residue of glycine;

X, X 7 , X 11 and X 15 are each O or NH;

R 1 , R 7 , R 11 and R 15 are each —CH 2 CH 2 —;

X 3 , X 5 , X 9 and X 13 are each O;

R 3 , R 5 , R 9 and R 13 are each —CH 2 —;

L k and L m form a carbamate; and

DHPD xx and DHPD dd are residues from 3,4 dihydroxyphenylethylamine.

21. The compound of claim 1 , wherein

L a is a residue of a poly(ethyleneglycol) bis(carboxymethyl)ether;

L c , L e , L g , and L, are absent;

ee is a value from 1 to about 11;

gg, ii, kk, and mm are each independently 0;

X, X 7 , X 11 and X 15 are each O or NH;

R 1 , R 7 , R 11 and R 15 are each —CH 2 CH 2 —;

X 3 , X 5 , X 9 and X 13 are each O;

R 3 , R 5 , R 9 and R 13 are each —CH 2 —;

L k and L m form an amide; and

DHPD xx and DHPD dd are residues from 3,4-dihydroxyhydrocinnamic acid (DOHA).

22. A bioadhesive construct, comprising:

a support suitable for tissue repair or reconstruction; and

a coating comprising a multihydroxyphenyl (DHPD) functionalized polymer (DHPp) of claim 1 .

23. The bioadhesive construct of claim 22 , further comprising an oxidant.

24. The bioadhesive construct of claim 22 , wherein the oxidant is formulated with the coating.

25. The bioadhesive construct of claim 22 , wherein the oxidant is applied to the coating.

26. The bioadhesive construct of claim 22 , wherein the support is a film, a mesh, a membrane, a nonwoven or a prosthetic.

27. A blend of a polymer and a compound of claim 1 .

28. The blend of claim 27 , wherein the polymer is present in a range of about 1 to about 50 percent by weight.

29. The blend of claim 28 , wherein the polymer is present in a range of about 1 to about 30 percent by weight.

30. A bioahesive construct comprising:

a support suitable for tissue repair or reconstruction; and

a coating comprising the blend of claim 27 .

31. The bioadhesive construct of claim 30 , further comprising an oxidant.

32. The bioadhesive construct of claim 30 , wherein the oxidant is formulated with the coating.

33. The bioadhesive construct of claim 30 , wherein the oxidant is applied to the coating.

34. The bioadhesive construct of claim 30 , wherein the support is a film, a mesh, a membrane, a nonwoven or a prosthetic.

35. A bioadhesive construct comprising:

a support suitable for tissue repair or reconstruction;

a first coating comprising a multihydroxyphenyl (DHPD) functionalized polymer (DHPp) of claim 1 and a polymer; and

a second coating coated onto the first coating, wherein the second coating comprises a multihydroxyphenyl (DHPD) functionalized polymer (DHPp) of claim 1 .

36. A bioadhesive construct comprising:

a support suitable for tissue repair or reconstruction;

a first coating comprising a first multihydroxyphenyl (DHPD) functionalized polymer (DHPp) of claim 1 and a first polymer; and

a second coating coated onto the first coating, wherein the second coating comprises a second multihydroxyphenyl (DHPD) functionalized polymer (DHPp) of claim 1 and a second polymer, wherein the first and second polymer may be the same or different and wherein the first and second DHPp can be the same or different.

37. A bioadhesive construct comprising:

a support suitable for tissue repair or reconstruction;

a first coating comprising a first multihydroxyphenyl (DHPD) functionalized polymer (DHPp) of claim 1 ; and

a second coating coated onto the first coating, wherein the second coating comprises a second multihydroxyphenyl (DHPD) functionalized polymer (DHPp) of claim 1 , wherein the first and second DHPp can be the same or different.

38. The compound of claim 20 , wherein L c is a residue of a polycaprolactone and L g is a residue of a polycaprolactone.