Organic articles

• US 6,447,920 B1
• Filed: 10/27/2000
• Issued: 09/10/2002
• Est. Priority Date: 04/30/1998
• Status: Expired due to Term

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Lohmann, Dieter, Chabrecek, Peter, Höpken, Jens
• Primary Examiner(s): TARAZANO, DONALD LAWRENCE
• Application Number:
  US09/697,860
• Time in Patent Office: 683 Days
• Field of Search: 428/520, 428/515, 428/522, 428/500, 428/423.1, 564/32, 564/48, 564/49, 351/160.R, 427/2.24, 427/487, 427/488, 427/491, 427/164, 427/508
• US Class Current: 428/423.1
• CPC Class Codes: C08F 290/00 Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups
• CPC Class Codes: C08F 290/04 Polymers provided for in subclasses C08C or C08F
• CPC Class Codes: C08J 7/16 with polymerisable compounds
• CPC Class Codes: G02B 1/043 Contact lenses
• CPC Class Codes: Y10T 428/31551 Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]
• CPC Class Codes: Y10T 428/31692 Next to addition polymer from unsaturated monomers
• CPC Class Codes: Y10T 428/31855 Of addition polymer from unsaturated monomers

Abstract

The invention relates to novel composite materials comprising (a) an inorganic or organic bulk material having covalently bound to its surface initiator moieties for radical polymerization; and (b) a hydrophilic surface coating obtainable by applying one or more different ethylenically unsaturated hydrophilic macromonomers of formula (1) as outlined in the claims to the bulk material surface provided with the initiator radicals and polymerizing said macromonomers. The composite materials 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 composite material comprising

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

and

(b) a hydrophilic surface coating obtainable by applying one or more different ethylenically unsaturated hydrophilic macromonomers to the bulk material surface provided with the initiator radicals and polymerizing said macromonomers,

wherein the macromonomers according to (b) are each of formula

wherein

R₁ is hydrogen, C₁-C₆-alkyl or a radical —

COOR′

;

R, R′ and

R₁′

are each independently of the other hydrogen or C₁-C₆-alkyl;

A is a direct bond or is a radical of formula

2. A composite material according to claim 1, wherein the bulk material is a natural or synthetic organic polymer having covalently bonded to its surface polymerization initiator radicals that thermally or photochemically initiate the radical polymerization of ethylenically unsaturated hydrophilic macromonomers.

3. A composite material according to claim 1, wherein the bulk material (a) of the composite material is a natural or synthetic organic polymer containing H-active groups on the surface that are coreactive with isocyanato groups, some or all of whose H atoms have been substituted by radicals of the formulae

wherein Z is bivalent —

O—

, —

NH—

or —

NR₂₂—

;

Z₁ is —

O—

, —

O—

(O)C—

, —

C(O)—

O—

or —

O—

C(O)—

O—

;

R₁₃ is H, C₁-C₁₂-alkyl, C₁-C₁₂-alkoxy or N—

C₁-C₁₂-alkylamino;

R₁₄ and R₁₅ are each independently of the other H, linear or branched C₁-C₈-alkyl, C₁-C₈-hydroxyalkyl or C₆-C₁₀-aryl, or the groups R₁₄—

(O)_b1— and

R₁₄—

(O)_b2—

together are —

(CH₂)_c—

wherein c is an integer from 3 to 5,

R₁₂ is a direct bond or linear or branched C₁-C₈-alkylene that is unsubstituted or substituted by —

OH and/or is uninterrupted or interrupted by one or more groups —

O—

, —

O—

C(O)—

or —

O—

C(O)—

O—

;

R₁₁′

is branched C₃-C₁₈-alkylene, unsubstituted or C₁-C₄-alkyl- or C₁-C₄-alkoxy-substituted C₆-C₁₀-arylene, or unsubstituted or C₁-C₄-alkyl- or C₁-C₄-alkoxy-substituted C₇-C₁₈-aralkylene, unsubstituted or C₁-C₄-alkyl- or C₁-C₄-alkoxy-substituted C₃-C₈-cycloalkylene, unsubstituted or C₁-C₄-alkyl- or C₁-C₄-alkoxy-substituted C₃-C₈-cycloalkylene-C_yH_2y—

or unsubstituted or C₁-C₄-alkyl- or C₁-C₄-alkoxy-substituted —

C_yH_2y—

(C₃-C₈-cycloalkylene)-C_yH_2y—

wherein y is an integer from 1 to 6;

R₁₆ independently has the same definitions as R₁₁′

or is linear C₃-C₁₈-alkylene;

R₂₂ is linear or branched C₁-C₆-alkyl;

T is bivalent —

O—

, —

NH—

, —

S—

, C₁-C₈-alkylene or

Z₂ is a direct bond or —

O—

(CH₂)_d—

wherein d is an integer from 1 to 6 and the terminal CH₂ group of which is linked to the adjacent T in formula (10c);

R₁₇ is H, C₁-C₁₂-alkyl, C₁-C₁₂-alkoxy, N—

C₁-C₁₂-alkylamino or —

NR₂₅R₂₆ wherein R₂₅ is C₁-C₈-alkyl and R₂₆ is H or C₁-C₈-alkyl;

R₁₈ is linear or branched C₁-C₈-alkyl, C₂-C₈-alkenyl or C₆-C₁₀-aryl-C₁-C₈-alkyl;

R₁₉ independently of R₁₈ has the same definitions as R₁₈ or is C₆-C₁₀-aryl, or R₁₈ and R₁₉ together are —

(CH₂)_e—

wherein e is an integer from 2 to 6;

R₂₀ and R₂₁ are each independently of the other linear or branched C₁-C₆-alkyl that may be substituted by C₁-C₄-alkoxy, or C₆-C₁₀-aryl-C₁-C₈-alkyl or C₂-C₈-alkenyl;

or R₂₀ and R₂₁ together are —

(CH₂)_f1—

Z₃—

(CH₂)_f2—

wherein Z₃ is a direct bond, —

O—

, —

S—

or —

NR₂₆—

, and R₂₆ is H or C₁-C₈-alkyl and f1 and f2 are each independently of the other an integer from 2 to 4; and

a, b1, b2 and b3 are each independently of the other 0 or 1;

subject to the provisos that b1 and b2 are each 0 when R₁₅ is H;

that the total of (b1+b2+b3) is not exceeding 2; and

that a is 0 when R₁₂ is a direct bond.

4. A composite material according to claim 3, wherein the bulk material (a) is an organic polymer containing H-active —

OH, —

NH₂ and/or —

NH—

groups on its surface, some or all of whose H atoms have been substituted by radicals of the formulae (12a) or (12b).

5. A composite material according to claim 1, wherein the hydrophilic macromonomer is a compound of formula (1), wherein R is hydrogen or methyl, R₁ is hydrogen, methyl or carboxyl, R₁′

is hydrogen and A is a radical of the formula (2a) or (2b).

6. A composite material according to claim 1, wherein the hydrophilic macromonomer is a compound of formula (1), wherein R is hydrogen or methyl, R₁ is hydrogen, methyl or carboxyl, R₁′

is hydrogen and A is a radical of the formula (2e).

7. A composite material according to claim 1, wherein the hydrophilic macromonomer is a compound of formula (1), wherein (oligomer) is the radical of a telomer of formula (3a).

8. A composite material according to claim 1, wherein the hydrophilic substituent of B or B′

is a non-ionic substituent selected from the group consisting of a radical C₁-C₆-alkyl which is substituted by one or more same or different substituents selected from the group consisting of —

OH, C₁-C₄-alkoxy and —

NR₉R₉′

, wherein R₉ and R₉′

are each independently of another hydrogen or unsubstituted or hydroxy-substituted C₁-C₆-alkyl or phenyl;

phenyl which is substituted by hydroxy, C₁-C₄-alkoxy or —

NR₉R₉′

, wherein R₉ and R₉′

are as defined above;

a radical —

COOY, wherein Y is C₁-C₂₄-alkyl which is unsubstituted or substituted by hydroxy, C₁-C₄-alkoxy, —

O—

Si(CH₃)₃, —

NR₉R₉′

wherein R₉ and R₉′

are as defined above, a radical —

O—

(CH₂CH₂O)_1-24—

E wherein E is hydrogen or C₁-C₆-alkyl, or a radical —

NH—

C(O)—

O—

G, wherein —

O—

G is the radical of a saccharide with 1 to 8 sugar units or is a radical —

O—

(CH₂CH₂O)_1-24—

E, wherein E is as defined above, or Y is C₅-C₈-cycloalkyl which is unsubstituted or substituted by C₁-C₄-alkyl or C₁-C₄-alkoxy, or is unsubstituted or C₁-C₄-alkyl- or C₁-C₄-alkoxy-substituted phenyl or C₇-C₁₂-aralkyl;

—

CONY₁Y₂ wherein Y₁ and Y₂ are each independently hydrogen, C₁-C₁₂-alkyl, which is unsubstituted or substituted for example by hydroxy, C₁-C₄-alkoxy or a radical —

O—

(CH₂CH₂O)_1-24—

E wherein E is as defined above, or Y₁ and Y₂ together with the adjacent N-atom form a five- or six-membered heterocyclic ring having no additional heteroatom or one additional oxygen or nitrogen atom;

a radical —

OY₃, wherein Y₃ is hydrogen;

or C₁-C₁₂-alkyl which is unsubstituted or substituted by —

NR₉R₉′

;

or is a radical —

C(O)—

C₁-C₄-alkyl; and

wherein R₉ and R₉′

are as defined above; and

a five- to seven-membered heterocyclic radical having at least one N-atom and being bound in each case via said nitrogen atom.

9. A composite material according to claim 8, wherein the non-ionic hydrophilic substituent is selected from the group consisting of a radical —

COOY, wherein Y is C₁-C₂-alkyl, C₂-C₃-alkyl, which is substituted by hydroxy, amino or N,N-di-C₁-C₂-alkylamino, or is a radical —

C₂-C₄-alkylene-NH—

C(O)—

O—

G wherein —

O—

G is the radical of trehalose or a cyclodextrin fragment with 1 to 8 sugar units each;

a radical —

CO—

NY₁Y₂, wherein Y₁ and Y₂ are each independently of the other hydrogen or C₁—

C₄-alkyl which is unsubstituted or substituted by hydroxy, or Y₁ and Y₂ together with the adjacent N-atom form a N—

C₁-C₂-alkylpiperazino or morpholino ring;

or a heterocyclic radical selected from the group consisting of N-pyrrolidonyl, 2- or 4-pyridinyl, 2-methylpyridin-5-yl, 2-, 3- oder 4-hydroxypyridinyl, N-ε

-capro-lactamyl, N-imidazolyl, 2-methylimidazol-1-yl, N-morpholinyl and 4-N-methylpiperazin-1-yl.

10. A composite material according to claim 1, wherein the hydrophilic substituent of B or B′

is an anionic substituent selected from the group consisting of C₁-C₆-alkyl which is substituted by —

SO₃H, —

OSO₃H, —

OPO₃H₂—

COOH or by a radical —

NH—

C(O)—

O—

G′

wherein G′

is the radical of lactobionic acid, hyaluronic acid or sialic acid;

phenyl which is substituted by one or more same or different substituents selected from the group consisting of —

SO₃H, —

COOH, —

OH and —

CH₂—

SO₃H;

—

COOH;

a radical —

COOY₄, wherein Y₄ is C₁-C₂₄-alkyl which is substituted by —

COOH, —

SO₃H, —

OSO₃H, or —

OPO₃H₂;

a radical —

CONY₅Y₆ wherein Y₅ is C₁-C₂₄-alkyl which is substituted by —

COOH, —

SO₃H, —

OSO₃H, or —

OPO₃H₂ and Y₆ independently has the meaning of Y₅ or is hydrogen or C₁-C₁₂-alkyl;

or —

SO₃H; and

a salt thereof.

11. A composite material according to claim 1, wherein the hydrophilic substituent of B or B′

is a cationic substituent selected from the group consisting of C₁-C₁₂-alkyl which is substituted by a radical —

NR₉R₉′

R₉″

⁺An⁻

, wherein R₉, R₉′ and

R₉″

are each independently of another hydrogen or unsubstituted or hydroxy-substituted C₁-C₆-alkyl or phenyl, and An⁻

is an anion; and

a radical —

C(O)OY₇, wherein Y₇ is C₁-C₂₄-alkyl which is substituted by —

NR₉R₉′

R₉″

⁺An⁻

and is further unsubstituted or substituted for example by hydroxy, wherein R₉, R₉′

, R₉″ and

An⁻

are as defined above.

12. A composite material according to claim 1, wherein the hydrophilic substituent of B or B′

is a zwitterionic substituent which is a radical of formula

13. A composite material according to claim 8, wherein B is a radical of formula

wherein R₅ is hydrogen or C₁-C₄-alkyl;

R₆ is a hydrophilic substituent selected from the group consisting of a radical C₁-C₆-alkyl which is substituted by one or more same or different substituents selected from the group consisting of —

OH, C₁-C₄-alkoxy and —

NR₉R₉′

, wherein R₉ and R₉′

are each independenty of another hydrogen or unsubstituted or hydroxy-substituted C₁-C₆-alkyl or phenyl;

phenyl which is substituted by hydroxy, C₁-C₄-alkoxy or —

NR₉R₉′

, wherein R₉ and R₉′

are as defined above;

a radical —

COOY wherein Y is C₁-C₂₄-alkyl which is unsubstituted or substituted by hydroxy, C₁-C₄-alkoxy, —

O—

Si(CH₃)₃, —

NR₉R₉′

wherein R₉ and R₉′

are as defined above, a radical —

O—

(CH₂CH₂O)_1-24—

E wherein E is hydrogen or C₁-C₆-alkyl, or a radical —

NH—

C(O)—

O—

G, wherein —

O—

G is the radical of a saccharide with 1 to 8 sugar units or is a radical —

O—

(CH₂CH₂O)_1-24—

E, wherein E is as defined above, or Y is C₅-C₈-cycloalkyl which is unsubstituted or substituted by C₁-C₄-alkyl or C₁-C₄-alkoxy, or is unsubstituted or C₁-C₄-alkyl- or C₁-C₄-alkoxy-substituted phenyl or C₇-C₁₂-aralkyl;

—

CONY₁Y₂ wherein Y₁ and Y₂ are each independently hydrogen, C₁-C₁₂-alkyl, which is unsubstituted or substituted for example by hydroxy, C₁-C₄-alkoxy or a radical —

O—

(CH₂CH₂O)_1-24—

E wherein E is as defined above, or Y₁ and Y₂ together with the adjacent N-atom form a five- or six-membered heterocyclic ring having no additional heteroatom or one additional oxygen or nitrogen atom;

a radical —

OY₃ wherein Y₃ is hydrogen;

or C₁-C₁₂-alkyl which is unsubstituted or substituted by —

NR₉R₉′

;

or is a radical —

C(O)—

C₁-C₄-alkyl; and

wherein R₉ and R₉′

are as defined above; and

a five- to seven-membered heterocyclic radical having at least one N-atom and being bound in each case via said nitrogen atom;

R₇ is C₁-C₄-alkyl, phenyl or a radical —

C(O)OY₉, wherein Y₉ is hydrogen or unsubstituted or hydroxy-substituted C₁-C₄-alkyl; and

R₈ is a radical —

C(O)Y₉′

or —

CH₂—

C(O)OY₉′

wherein Y₉′

independently has the meaning of Y₉; and

B′

independently has one of the meanings given above for B or is the radical of a hydrophobic comonomer.

14. A composite material according to claim 1, wherein (oligomer) denotes a radical of formula (3a), and the radical —

(alk)—

S—

[B]_p—

[B′

]_q—

Q is a radical of formula

wherein (alk) is C₂-C₄-alkylene, R₅ and R₅′

are each independently hydrogen or methyl, Q is a monovalent group that is suitable to act as a polymerization chain-reaction terminator, p and q are each independently an integer from 0 to 100 wherein the total of (p+q) is an integer from 5 to 100, and R₆ and R₆′

are each independently a radical —

COOY, wherein Y is C₁-C₄-alkyl, C₂-C₄-alkyl, which is substituted by one or two substituents selected from the group consisting of hydroxy and —

NR₉R₉′

wherein R₉ and R₉′

are each independently of another hydrogen or C₁-C₂-alkyl, or is a radical —

CH₂CH₂—

O—

(CH₂CH₂—

O)_1-12—

E wherein E is hydrogen or C₁-C₂-alkyl, or is a radical —

C₂-C₄-alkylene-NH—

C(O)—

O—

G wherein —

O—

G—

is the radical of trehalose or a cyclodextrin fragment with 1 to 8 sugar units each;

a radical —

CO—

NY₁Y₂, wherein Y₁ and Y₂ are each independently of the other hydrogen or C₁-C₄-alkyl which is unsubstituted or substituted by hydroxy, or Y₁ and Y₂ together with the adjacent N-atom form a N—

C₁-C₂-alkylpiperazino or morpholino ring;

a heterocyclic radical selected from the group consisting of N-pyrrolidonyl, 2- or 4-pyridinyl, 2-methylpyridin-5-yl, 2-, 3-oder 4-hydroxypyridinyl, N-ε

-caprolactamyl, N-imidazolyl, 2-methylimidazol-1-yl, N-morpholinyl and 4-N-methylpiperazin-1-yl;

C₁-C₂-alkyl, which is substituted by one or more substituents selected from the group consisting of —

SO₃H and —

OPO₃H₂;

phenyl which is substituted by —

SO₃H or sulfomethyl;

—

COOH;

a radical —

COOY₄, wherein Y₄ is C₂-C₆-alkyl which is substituted by —

COOH, —

SO₃H, —

OSO₃H or —

OPO₃H₂;

a radical —

CONY₅Y₆ wherein Y₅ is C₁-C₆-alkyl substituted by sulfo, and Y₆ is hydrogen;

or —

SO₃H;

or a suitable salt thereof.

15. A composite material according to claim 14, wherein p is an integer from 10 to 50, q is the number 0, R₅ is hydrogen and R₆ is —

C(O)NH₂.

16. A composite material according to claim 14, wherein p is an integer from 10 to 50, q is the number 0, R₅ is methyl or hydrogen and R₆ is a radical —

COO(CH₂)_2-4—

NHC(O)—

O—

G wherein —

O—

G is the radical of trehalose.

17. A composite material according to claim 1, wherein the macromonomer applied to the hydrophilic surface and polymerized there is of formula

wherein R is hydrogen or methyl, (alk) is C₂-C₄-alkylene, R₅ is hydrogen or methyl, p is an integer of 5 to 50, Q is a monovalent group that is suitable to act as a polymerization chain-reaction terminator, and R₆ is a radical —

COO—

C₁-C₂-alkyl, —

COO—

(CH₂)_2-4—

OH, —

CONH₂, —

ON(CH₃)₂, —

CONH—

(CH₂)₂—

OH,

or —

COO(CH₂)_2-4—

NHC(O)—

O—

G wherein —

O—

G is the radical of trehalose or a cyclodextrin fragment with a maximum of 8 sugar units.

18. A composite material according to claim 1, wherein (oligomer) is a radical of the formula (3b) or (3b′

).

19. A composite material according to claim 1, wherein the polymerization of the macromonomers on the bulk material surface is initiated by the action of irradiation.

20. A composite material according to claim 19, wherein the polymerization is initiated by the action of UV radiation for a time period of 0.5 to 5 minutes.

21. A composite material according claim 1, wherein the hydrophilic surface coating is obtainable by grafting at least one macromonomer to the bulk material surface with formation of a bottle-brush structure composed of tethered chain.

22. A composite material according to claim 1, wherein the hydrophilic surface coating has a coating thickness of from 0.01 to 50 μ

m.

23. A process for the manufacture of a composite material according to claim 1, which comprises the steps:

(a) providing an inorganic or organic bulk material having covalently bonded on its surface polymerization initiator radicals;

(b) applying a coating of one or more different ethylenically unsaturated hydrophilic macromonomers of formula (1) according to claim 1 to the bulk material surface provided with the initiator radicals, and

(c) polymerizing the coating of unsaturated hydrophilic macromonomers by irradiation.

24. A process according to claim 23, wherein the inorganic or organic bulk material is a biomedical device.

25. Biomedical device comprising a composite material according to claim 1.

26. Biomedical device according to claim 25 wherein the biomedical device is a contact lens, intraocular lens or artificial cornea.

27. Biomedical device according to claim 26, which is a contact lens and has a tear break up time (TBUT) of >

15 seconds.

28. A composite material according to claim 1, wherein p and q in formula (3a) are each independently an integer from 0 to 100, wherein the total of (p+q) is an integer from 5 to 100.

29. A composite material according to claim 1, which is a biomedical device comprising a bulk material that comprises a polysiloxane, perfluoropolyether, fluorinated poly(meth)acrylate, polyalkyl(meth)acrylates, or fluorinated polyolefin.

30. A composite material according to claim 29, which is a contact lens, intraocular lens, or artificial cornea.

31. A composite material according to claim 1, wherein the initiator moieties are derived from a functional photoinitiator of formula

b1 and b2 are each 0;

Z and Z1 are each bivalent —

O—

;

b3 is 0 or 1;

R₁₄ is C₁-C₄-alkyl or phenyl, or both groups R₁₄ together are tetramethylene or pentamethylene;

R₁₅ is C₁-C₄-alkyl or H,

R₁₃ is hydrogen;

a and a1 are each independently 0 or 1;

R₁₂ is linear or branched C₂-C₄-alkylene, or is a direct bond, in which case a is 0;

R₁₁′

is branched C₅-C₁₀-alkylene, phenylene or phenylene substituted by from 1 to 3 methyl groups, benzylene or benzylene substituted by from 1 to 3 methyl groups, cyclohexylene or cyclohexylene substituted by from 1 to 3 methyl groups, cyclohexyl-C_yH_2y—

or —

C_yH_2y-cyclohexyl-C_yH_2y—

or cyclohexyl-C_yH_2y—

or —

C_yH_2y-cyclohexyl-C_yH_y—

substituted by from 1 to 3 methyl groups, wherein y is 1 or 2;

T is bivalent —

O—

, —

NH—

, —

S—

or —

(CH₂)_y—

wherein y is an integer from 1 to 6;

Z₂ is a direct bond or —

O—

(CH₂)_y—

wherein y is an integer from 1 to 6 and the terminal CH₂ group of which is linked to the adjacent T in formula (10c);

R₁₇ is H, C₁-C₁₂-alkyl or C₁-C₁₂-alkoxy;

R₁₈ is linear C₁-C₈-alkyl, C₂-C₈-alkenyl or C₆-C₁₀-aryl-C₁-C₈-alkyl;

R₁₉ independently of R₁₈ has the same definitions as R₁₈ or is C₆-C₁₀-aryl, or R₁₈ and R₁₉ together are —

(CH₂)_e—

wherein e is an integer from 2 to 6;

R₂₀ and R₂₁ are each independently of the other linear or branched C₁-C₆-alkyl that may be substituted by C₁-C₄-alkoxy, or C₆-C₁₀-aryl-C₁-C₈-alkyl or C₂-C₈-alkenyl;

or R₂₀ and R₂₁ together are —

(CH₂)_f1—

Z₃—

(CH₂)_f2—

wherein Z₃ is a direct bond, —

O—

, —

S—

or —

NR₂₆—

, and R₂₆ is H or C₁-C₈-alkyl and f1 and f2 are each independently of the other an integer from 2 to 4; and

R₁₆ is branched C₆-C₁₀-alkylene, phenylene or phenylene substituted by from 1 to 3 methyl groups, benzylene or benzylene substituted by from 1 to 3 methyl groups, cyclohexylene or cyclohexylene substituted by from 1 to 3 methyl groups, cyclohexylene-CH₂—

or cyclohexylene-CH₂—

substituted by from 1 to 3 methyl groups.