Covalently-bound, hydrophilic coating compositions for surgical implants

• US 6,723,815 B2
• Filed: 05/13/2003
• Issued: 04/20/2004
• Est. Priority Date: 09/02/1999
• Status: Expired due to Term

• Current Assignee: Alcon Incorporated
• Original Assignee: Alcon Incorporated
• Inventors: Callaghan, Thomas A., Leboeuf, Albert R.
• Primary Examiner(s): Zalukaeva, Tatyana
• Application Number:
  US10/437,325
• Publication Number:
  US 20030208013A1
• Time in Patent Office: 343 Days
• Field of Search: 526/264, 526/258, 526/263, 526/328, 526/328.5, 428/451, 428/500, 623/56, 623/6.11, 427/2.24, 427/162, 427/164, 427/284
• US Class Current: 526/303.1
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: C08L 33/06 of esters containing only carbon, hydrogen and oxygen, which oxygen atoms are present only as part of the carboxyl radical

Abstract

Covalently-bound, hydrophilic copolymer coatings for implants are disclosed. The copolymer coatings comprise a hydrophobic aryl acrylic monomer, a hydrophilic monomer selected from the group consisting of hydroxyalkyl (meth)acrylates, n-vinyl pyrrolidone and acrylamides, and a reactive plasticizer.

Claims

1. A copolymeric coating composition for a surgical implant wherein the coating composition is capable of absorbing from at least 5 to about 90% water and comprises

(i) a hydrophobic aryl acrylic monomer of the formula

wherein:

A is H, CH₃, CH₂CH₃, or CH₂OH;

B is (CH₂)_m or [O(CH₂)₂]_n;

C is (CH₂)_w;

m is 2-6;

n is 1-10;

Y is nothing, O, S, or NR, provided that if Y is O, S, or NR, then B is (CH₂)_m;

R is H, CH₃, C_nH_2n+1(n=1-10), iso-OC₃H₇, C₆H₅, or CH₂C₆H₅;

w is 0-6, provided that m+w≦

8; and

D is H, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₆H₅, CH₂C₆H₅ or halogen;

(ii) a hydrophilic monomer selected from the group consisting of hydroxyalkyl (meth)acrylates;

n-vinyl pyrrolidone and acrylamides;

(iii) a reactive plasticizer selected from the group consisting of polyethylene glycol (200-2000) mono(meth)acrylates and polyethylene glycol (200-2000) monomethylether mono(meth)acrylates; and

(iv) a covalent cross-linking agent.

2. The coating composition of claim 1 wherein the hydrophilic monomer is selected from the group consisting of hydroxyalkyl (meth)acrylates and n-vinyl pyrrolidone.

3. The coating composition of claim 2 wherein the coating composition comprises a hydroxyalkyl (meth)acrylate and n-vinyl pyrrolidone.

4. The coating composition of claim 1 wherein the hydrophilic monomer is selected from the group consisting of methacrylamide;

ethacrylamide;

propacrylamide;

dimethyl (meth)acrylamide;

diethyl (meth)acrylamide and dipropyl (meth)acrylamide.

5. The coating composition of claim 1 wherein the coating composition is capable of absorbing from about 30 to about 80% water.

6. The coating composition of claim 1 wherein the coating composition is capable of absorbing from about 40 to about 60% water.

7. The coating composition of claim 1 wherein A is CH₃, B is (CH₂)_m, m is 2-5, Y is nothing or O, w is 0-1, and D is H.

8. The coating composition of claim 1 wherein the hydrophobic aryl acrylic monomer is selected from the group consisting of 2-phenylethyl methacrylate;

3-phenylpropyl methacrylate;

4-phenylbutyl methacrylate;

5-phenylpentyl methacrylate;

2-benzyloxyethyl methacrylate; and

3-benzyloxypropyl methacrylate.

9. The coating composition of claim 1 wherein the coating composition comprises from about 10-60% of 2-phenylethyl (meth)acrylate, from about 5-70% of hydrophilic monomer and from about 20-40% of reactive plasticizer.

10. The coating composition of claim 1 wherein the composition comprises from about 20-50% of 2-phenylethyl methacrylate, from about 5-20% of a mixture of 1,3- and 2,3-dihydroxypropyl methacrylate, from about 0-40% of n-vinyl pyrrolidone, and from 20-40% of polyethylene glycol (400) monomethylether monomethacrylate.

11. The coating composition of claim 1 wherein the cross-linking agent is selected from the group consisting of blocked isocyanates and peroxides.

12. The coating composition of claim 11 wherein the cross-linking agent is selected from the group consisting of imidazole blocked isocyanatoethyl methacrylate;

di-imidazole blocked 1,12-isocyanatododecane;

benzoyl peroxide; and

2,4-dichlorobenzoyl peroxide.

13. The coating composition of claim 1 wherein the coating composition further comprises one or more ingredients selected from the group consisting of UV absorbers that are copolymerizable with the hydrophobic aryl acrylic monomer and hydrophilic monomer;

blue-light blocking colorants that are copolymerizable with the hydrophobic aryl acrylic monomer and hydrophilic monomer; and

chain transfer agents.

14. The coating composition of claim 1 wherein the reactive plasticizer is polyethylene glycol (400) monomethylether monomethacrylate.

15. The coating composition of claim 13 wherein the coating composition comprises a chain transfer agent selected from the group consisting of 1-dodecanethiol and 2-mercaptoethanol.

16. A coated surgical implant comprising a coating and a substrate wherein the coating and the substrate are not identical, the coating is attached to the substrate by covalent bonds, the coating is from about 0.01 to about 1 μ

m thick, and the coating comprises a covalently cross-linked copolymer comprising

(i) a hydrophobic aryl acrylic monomer of the formula

wherein;

A is H, CH₃, CH₂CH₃, or CH₂OH;

B is (CH₂)_m or [O(CH₂)₂]_n;

C is (CH₂)_w;

m is 2-6;

n is 1-10;

Y is nothing, O, S, or NR, provided that if Y is O, S, or NR, then B is (CH₂)_m;

R is H, CH₃, C_nH_2n+1(n=1-10), iso-OC₃H₇, C₆H₅, or CH₂C₆H₅;

w is 0-6, provided that m+w≦

8; and

D is H, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₆H₅, CH₂C₆H₅ or halogen;

(ii) a hydrophilic monomer selected from the group consisting of hydroxyalkyl (meth)acrylates;

n-vinyl pyrrolidone and acrylamides;

(iii) a reactive plasticizer selected from the group consisting of polyethylene glycol (200-2000) mono(meth)acrylates and polyethylene glycol (200-2000) monomethylether mono(meth)acrylates;

and a covalent cross-linking agent, and wherein the covalently cross-linked copolymer is capable of absorbing from at least 5 to about 90% water.

17. The coated surgical implant of claim 16 wherein the substrate comprises a hydrophobic acrylic material.

18. The coated surgical implant of claim 16 wherein the covalently cross-linked copolymer comprises a hydrophilic monomer selected from the group consisting of hydroxyalkyl (meth)acrylates and n-vinyl pyrrolidone.

19. The coated surgical implant of claim 17 wherein the covalently cross-linked copolymer comprises a hydroxyalkyl (meth)acrylate and n-vinyl pyrrolidone.

20. The coated surgical implant of claim 16 wherein the covalently cross-linked copolymer is capable of absorbing from about 30 to about 80% water.

21. The coated surgical implant of claim 16 wherein the covalently cross-linked copolymer comprises from about 10-60% of the hydrophobic aryl acrylic monomer, from about 5-70% of hydrophilic monomer and from about 20-40% of reactive plasticizer.

22. The coated surgical implant of claim 16 wherein the implant is selected from the group consisting of intraocular lenses and contact lenses.

23. A method of applying a coating to a surgical implant comprising the steps of:

a) preparing an uncross-linked copolymer comprising (i)

wherein;

A is H, CH₃, CH₂CH₃, or CH₂OH;

B is (CH₂)_m or [O(CH₂)₂]_n;

C is (CH₂)_w;

m is 2-6;

n is 1-10;

Y is nothing, O, S, or NR, provided that if Y is O, S, or NR, then B is (CH₂)_m;

R is H, CH₃, C_nH_2n+1(n=1-10), iso-OC₃H₇, C₆H₅, or CH₂C₆H₅;

w is 0-6, provided that m+w≦

8; and

D is H, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₆H₅, CH₂C₆H₅ or halogen;

(ii) a hydrophilic monomer selected from the group consisting of hydroxyalkyl (meth)acrylates;

n-vinyl pyrrolidone; and

acrylamides; and

(iii) a reactive plasticizer selected from the group consisting of polyethylene glycol (200-2000) mono(meth)acrylates and polyethylene glycol (200-2000) monomethylether mono(meth)acrylates, and optionally (iv) a latent covalent cross-linking agent, such that the copolymer is capable of absorbing from at least 5 to about 90% water;

b) forming a coating solution by dissolving the copolymer in an organic solvent and if the copolymer does not contain a latent cross-linking agent then adding covalent a cross-linking agent to the solution;

c) applying the coating solution to the implant; and

d) drying the coating solution on the implant, such that the latent cross-linking agent or covalent cross-linking agent is activated and the copolymer is covalently bound to the implant.