Bottle-brush type coatings with entangled hydrophilic polymer

• US 20030008063A1
• Filed: 05/09/2002
• Published: 01/09/2003
• Est. Priority Date: 05/21/2001
• Status: Active Grant

• Current Assignee: Alcon Incorporated
• Original Assignee: Novartis Ag
• Inventors: Leukel, Jorg, Lohmann, Dieter, Chabrecek, Peter
• Granted Patent: US 6,835,410 B2
• Time in Patent Office: Days
• US Class Current: 427/2.1
• CPC Class Codes: A61L 27/34 Macromolecular materials

Abstract

The invention relates to a process for coating a material surface comprising the steps of:

(a) providing an inorganic or organic bulk material having covalently bound to its surface initiator moieties for radical polymerization;

(b) graft polymerizing a hydrophilic ethylenically unsaturated macromonomer from the bulk material surface in the presence of a biocompatible hydrophilic polymer being devoid of polymerizable ethylenically unsaturated groups and thereby entrapping said hydrophilic polymer within the polymer matrix formed by the polymerization of the macromonomer.

Composite materials obtainable according to the process of the invention have desirable characteristics regarding adherence to the substrate, durability, hydrophilicity, wettability, biocompatibility and permeability and are thus useful for the manufacture of biomedical articles such as ophthalmic devices.

Claims

1. A process for coating a biomedical device, which comprises:

(a) providing an inorganic or organic bulk material having covalently bound to its surface initiator moieties for radical polymerization;

(b) graft polymerizing a hydrophilic ethylenically unsaturated macromonomer from the bulk material surface in the presence of a biocompatible hydrophilic polymer being devoid of polymerizable ethylenically unsaturated groups and thereby entrapping said hydrophilic polymer within the polymer matrix formed by the polymerization of the macromonomer.

2. A process according to claim 1, wherein the material surface is the surface of a biomedical device, particularly a contact lens, intraocular lens or artificial cornea.

3. A process according to claim 1 or 2, wherein the attachment of the initiator moieties to the bulk material comprises:

(a) providing a bulk material surface with H-active groups;

(b) reacting the bulk material surface with a functional polymerization initiator having a functional group that is co-reactive to said H-active groups.

4. A process according to claim 1 or 2, wherein the attachment of the initiator moieties to the bulk material comprises:

(a) reacting the material surface with a compound of formula

wherein R₂₉ is C₁-C₄-alkyl, C₁-C₄-alkoxy, hydroxy, sulfo, nitro, trifluoromethyl or halogen,

g is an integer from 0 to 2,

L₁ is a group, which functions as a triggerable precursor for carbene or nitrene formation,

L₂ is amino, C₁-C₄-alkylamino, hydroxy, glycidyl, carboxy or a derivative thereof, isocyanato or isothiocyanato, or is a radical of formula

—

[L₃]_h—

(spacer)—

L₂′

 

 

(1a)

L₂′

is amino, C₁-C₄-alkylamino, hydroxy, carboxy or a derivative thereof, isocyanato, isothiocyanato, —

O-glycidyl or —

O—

C(O)—

(CH₂)_h1—

X₂, wherein h1 is from 1 to 4 and X₂ is carboxy or a derivative thereof,

L₃ is —

NH—

, —

NC₁—

C₆-alkyl-, —

O—

, —

C(O)O—

, —

C(O)NH—

, —

NHC(O)NH—

, —

NHC(O)O—

or —

OC(O)NH—

;

(spacer) is linear or branched C₁-C₂₀₀-alkylene which may be substituted by hydroxy and/or interrupted by —

O—

except for C₁-alkyl, or is C₃-C₈-cycloalkylene, C₃-C₈-cycloalkylene-C₁-C₆-alkylene, C₃-C₈-cycloalkylene-C₁-C₂-alkylene-C₃-C₈-cycloalkylene or C₁-C₆-alkylene-C₃-C₈-cycloalkylene-C₁-C₆-alkylene; and

h is the number 0 or 1;

(b) reacting the so modified surface with a functional polymerization initiator having a functional group that is co-reactive to L₂ or L₂′

.

5. A process according to any one of claims 1, 2 or 4, wherein step (a) comprises applying the compound of formula (1) to the material surface and fixing said compound of formula (1) onto the material surface using radiation, in particular UV or visible light.

6. A process according to any one of claims 1, 2, 4 and 5, wherein L₁ is the radical of formula

7. A process according to any one of claims 1, 2, 4, 5 and 6, wherein L₁ is the azide radical —

N₃, g is 0 or 1, R₂₉ is methyl, methoxy, hydroxy or nitro, and L₂ is amino, carboxy, a carboxy derivative, isocyanato, isothiocyanato or a radical of formula —

L₃—

(spacer)—

L₂′

, wherein L₃ is —

NH—

—

C(O)O—

or —

C(O)NH—

, (spacer) is linear C₂-C₁₂-alkylene or —

(C₂-C₃-alkylene)—

O—

(CH₂CH₂O)_18-160—

(C₂-C₃-alkylene)—

, and L₂′

is carboxy, a carboxy derivative or a radical —

O—

C(O)—

(CH₂)₂—

X₂, wherein X₂ is carboxy or a carboxy derivative.

8. A process according to claims 3 or 4, wherein the functional polymerization initiator is a photoinitiator of formula

9. A process according to any one of claims 1 to 8, wherein a macromonomer of formula

10. A process according to claim 9, wherein R is hydrogen or methyl, R₃₂ and R₃₂′

are each hydrogen, A is a radical of the formula (5a) and (oligomer) is a radical of formula (6a).

11. A process according to claim 9 or 10, wherein (oligomer) is a radical of formula

12. A process according to any one of claims 1 to 11, wherein in step (b) a macromonomer of formula

13. A process according to any one of claims 1 to 12, wherein the biocompatible hydrophilic polymer applied in step (b) is selected from the group consisting of hyaluronic acid, chondriotin sulfate, heparin, dextran and mucin.

14. A process according to any one of claims 1 to 12, wherein the biocompatible hydrophilic polymer applied in step (b) is selected from the group consisting of carboxymethylcellulose, carboxyalkylchitin and carboxyalkylchitosan.

15. A process according to any one of claims 1 to 12, wherein the biocompatible hydrophilic polymer applied in step (b) is selected from the group consisting of a polyoxyalkylene amine, polyethylene glycol, poly-HEMA, a crosslinked polyacrylic acid based polymer, polyacrylamide, polyvinylpyrrolidone and polyvinyalcohol.

16. A process according to claim 1, wherein in step (b) an additional bioactive compound, for example, a polyquat, is added.

17. A composite material obtainable by the process of any one of claims 1 to 16.

18. A composite material according to claim 17, which is a biomedical device, preferably an ophthalmic device such as a contact lens, intraocular lens or artificial cornea.

19. Use of a composite material according to claim 17 for the manufacture of an ophthalmic device, particularly for the manufacture of a contact lens, intraocular lens or artificial cornea.