Polysiloxane-polyol macromers, their preparation and their use

• US 6,043,328 A
• Filed: 11/17/1997
• Issued: 03/28/2000
• Est. Priority Date: 05/19/1995
• Status: Expired due to Term

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Domschke, Angelika, Lohmann, Dieter, Hopken, Jens
• Primary Examiner(s): MERRIAM, ANDREW EDWIN
• Application Number:
  US08/952,416
• Time in Patent Office: 862 Days
• Field of Search: 523/106, 523/107, 528/32, 525/54.2, 525/326.5, 526/238.2, 526/238.23, 526/279, 526/301, 526/302, 526/304
• US Class Current: 526/279
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: B05D 1/62 Plasma-deposition of organic layers plasma deposition in general C23C14/00, C23C16/00
• CPC Class Codes: B29C 39/42 Casting under special conditions, e.g. vacuum
• CPC Class Codes: B29C 71/00 After-treatment of articles without altering their shape; Apparatus therefor B29C44/56, B29C73/00 take precedence; surface shaping B29C59/00 ; for joined or sealed parts B29C66/03; after-treatment specially adapted for vulcanising tyres B29D30/0633
• CPC Class Codes: B29D 11/00076 enabling passage of fluids, e.g. oxygen, tears, between the area under the lens and the lens exterior
• CPC Class Codes: B29L 2011/0041 Contact lenses
• CPC Class Codes: C08G 18/10 Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
• CPC Class Codes: C08G 18/48 Polyethers
• CPC Class Codes: C08G 18/4833 Polyethers containing oxyethylene units
• CPC Class Codes: C08G 18/5015 having fluorine atoms
• CPC Class Codes: C08G 18/61 Polysiloxanes
• CPC Class Codes: C08G 18/63 Block or graft polymers obtained by polymerising compounds having carbon-to-carbon double bonds on to polymers
• CPC Class Codes: C08G 18/672 Esters of acrylic or alkyl acrylic acid having only one group containing active hydrogen
• CPC Class Codes: C08G 18/8116 esters of acrylic or alkylacrylic acid having only one isocyanate or isothiocyanate group
• CPC Class Codes: C08G 18/8175 with esters of acrylic or alkylacrylic acid having only one group containing active hydrogen
• CPC Class Codes: C08L 33/00 Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 39/06 Homopolymers or copolymers of N-vinyl-pyrrolidones
• CPC Class Codes: C08L 51/08 grafted on to macromolecular compounds obtained otherwise than by reactions only involving unsaturated carbon-to-carbon bonds
• CPC Class Codes: C08L 51/085 on to polysiloxanes
• CPC Class Codes: C08L 83/04 : Polysiloxanes
• CPC Class Codes: G02B 1/043 : Contact lenses
• CPC Class Codes: Y10S 525/903 : Interpenetrating network
• CPC Class Codes: Y10S 525/936 : Encapsulated chemical agent
• CPC Class Codes: Y10S 525/937 : Utility as body contact e.g. implant, contact lens or I.U.D.

Abstract

The present invention describes a polysiloxane-polyol macromer which is uninterrupted or interrupted by a bivalent structural element and furthermore carries at least one polymerizable segment on a polyol segment; a polymer comprising a polymerization product of at least one macromer according to the invention and, if appropriate, of at least one vinylic comonomer; intermediates; processes for the preparation of a macromer and a polymerization product; moldings, contact lenses, corneal implants or biomedical articles of a polymerization product; and furthermore the use of a macromer according to the invention or of a polymer prepared therefrom for coating a substrate.

Claims

1. A macromonomer comprising at least one section of the formula (I) ##STR15## in which (a) is a polysiloxane segment derived from a compound of the formula (III) ##STR16## in which n is an integer from 5 to 500;

99.8-25% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are alkyl and 0.2-75% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are partly fluorinated alkyl, aminoalkyl, alkenyl, aryl, cyanoalkyl, alk--NH--alk--NH₂ or alk--(OCH₂)_m --(OCH₂)_p --OR₇, in which

R₇ is hydrogen or lower alkyl,

alk is alkylene, and

m and p independently of one another are an integer from 0 to 10, one molecule of the formula (III) containing at least one primary amino or hydroxyl group;

wherein the radicals R₄ and R₅ are 1-50 times pendently aminoalkyl or hydroxyalkyl;

(b) is a polyol segment derived from a carbohydrate, carbohydrate monolactone, carbohydrate dilactone, a 1,3-polyol, or a polyvinyl alcohol,

Z is a segment formed by a condensation reaction and is

(c) or a group X₁, in which segment (c) is defined as X₂ --R--X₂, in which R is a bivalent radical of an organic compound having up to 20 C atoms and each X₂ independently of the other is a bivalent radical which contains at least one carbonyl group, and in which X₁ is defined as X₂, and in which

(d) is a radical of the formula (II)

space="preserve" listing-type="equation">X.sub.3 --L--(Y).sub.k --P.sub.1 (II)

in which P₁ is a group which can be polymerized by free radicals;

Y and X₃ independently of one another are a bivalent radical which contains at least one carbonyl group;

k is 0 or 1; and

L is a bond or a divalent radical having up to 20 C atoms of an organic compound.

2. A macromer according to claim 1, in which a polysiloxane segment (a) is linked a total of 1-50 times via a group Z with a segment (b) or another segment (a), Z in an a-Z-a sequence always being a segment (c).

3. A macromer according to claim 1, in which a polysiloxane segment is derived from a compound of the formula (III) in which the radicals R₁, R₂, R₃, R₄, R₅ and R₆ are a total of 1-50 times independently either terminally or pendently aminoalkyl or hydroxyalkyl.

4. A macromer according to claim 1, in which a polysiloxane segment (a) is derived from a compound of the formula (III) in which

95-29% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are alkyl and 5-71% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are partly fluorinated alkyl, aminoalkyl, alkenyl, aryl, cyanoalkyl, alk--NH--alk--NH₂ or alk--(OCH₂ CH₂)_m --(OCH₂)_p --R₇.

5. A macromer according to claim 1, in which n is an integer from 5 to 400.

6. A macromer according to claim 1, in which the two terminal radicals R₁ and R₆ are aminoalkyl or hydroxyalkyl.

7. A macromer according to claim 1, in which the radicals R₄ and R₅ are 2-30 times, pendently aminoalkyl or hydroxyalkyl.

8. A macromer according to claim 1, in which the radicals R₁, R₂, R₃, R₄, R₅ and R₆ are a total of 1-50 times independently both terminally and pendently aminoalkyl or hydroxyalkyl.

9. A macromer according to claim 1, in which Z is X₁.

10. A macromer according to claim 9, in which X₁ is a carbonyl group which is flanked not more than 2 times by --O--, --CONH--, --NHCO-- or --NH--.

11. A macromer according to claim 10, in which X₁ is a carbonyl, ester, amide, urethane, urea or carbonate group.

12. A macromer according to claim 1, in which X₂ has the same meaning as X₁.

13. A macromer according to claim 10, in which X₂ is an ester, amide, urethane, carbonate or urea group.

15. A macromer according to claim 1, which is a compound of the formula (IV) ##STR18## in which the variables are as defined above.

17. A macromer according to claim 1, containing a section of the formula (VI) ##STR20## in which a linear sequence is present, in which x is 0, 1 or 2,

q has an average numerical value of 1-20, and in which

the segments (b) in a macromer according to the formula (VI) are linked in total (per molecule) with up to 20 polymerizable segments (d).

19. A macromer according to claim 1, in which a polyol segment (b) is derived from a polyol which carries no lactone group and the group Z is a segment (c).

20. A macromer according to claim 1, in which a polyol segment (b) is derived from a monosaccharide, polyvinyl alcohol (PVA) or cyclodextrin.

21. A macromer according to claim 1, in which a segment (b) carries at least one vinylic polymerizable segment (d), the segment (d) being linked via the bivalent radical X₃ thereof to an amino or hydroxyl group, of a segment (b), which hydroxyl group is reduced by a hydrogen atom.

22. A macromer according to claim 1, in which, per macromer molecule according to the invention, a vinylic polymerizable segment (d) is incorporated either terminally or pendently preferably 1-20 times.

23. A macromer according to claim 1, in which, per macromer molecule according to the invention, a vinylic polymerizable segment (d) is incorporated terminally and also pendently.

24. A macromer according to claim 1, in which P₁ is alkenyl, alkenylaryl or alkenylarylenealkyl having up to 20 C atoms.

25. A macromer according to claim 1, in which L is alkylene, arylene, a saturated bivalent cycloaliphatic group having 6 to 20 carbon atoms, arylenealkylene, alkylenearylene, alkyenearylenealkylene or arylenealkylenearylene.

26. A macromer according to claim 1, in which L is a bond.

27. A macromer according to claim 1, in which Y is a carbonyl, ester, amide or urethane group.

28. A macromer according to claim 1, in which k is 0.

29. A macromer according to claim 1, in which X₃ is a urethane, urea, ester, amide or carbonate group.

30. A macromer according to claim 1, in which a segment (d) is derived from acrylic acid, methacrylic acid, methacryloyl chloride, 2-isocyanatoethyl methacrylate (IEM), allyl isocyanate, vinyl isocyanate, the isomeric vinylbenzyl isocyanates or adducts of hydroxyethyl methacrylate (HEMA) and 2,4-tolylene diisocyanate (TDI) or isophorone diisocyanate (IPDI), in particular the 1:

1 adduct.

31. A macromer according to claim 1, in which a segment (d) is incorporated either terminally or pendently or as a terminal/pendent mixture 5 times per molecule.

32. A macromer according to claim 1, in which R is alkylene, arylene, alkylenearylene, arylenealkylene or arylenealkylenearylene having up to 20 carbon atoms, a saturated bivalent cycloaliphatic group having 6 to 20 carbon atoms or cycloalkylenealkylenecycloalkylene having 7 to 20 carbon atoms.

33. A macromer according to claim 1, in which a segment (c) is derived from hexane 1,6-diisocyanate, 2,2,4-trimethylhexane 1,6-diisocyanate, tetramethylene diisocyanate, phenylene 1,4-diisocyanate, toluene 2,4-diisocyanate, toluene 2,6-diisocyanate, m- or p-tetramethylxylene diisocyanate, isophorone diisocyanate or cyclohexane 1,4-diisocyanate.

34. A macromer according to claim 1, in which the weight-average molecular weight of the macromer is in the range from about 300 to 30,000.

37. A macromer according to claim 1, which is a compound of the formula (X)

38. A macromer according to claim 1, which is a compound of the formula (XI)

39. A macromer according to claim 1, in which the ratio of the number of segments (a) and (b) is in a range of (a):

(b)=3;

4, 2;

3, 1;

2, 1;

1, 1;

3 or 1;

4.

40. A macromer according to claim 1, in which the total sum of segments (a) and (b) or, where appropriate, (a) and (b) and (c) is in a range from 2 to 50.

48. A polymer comprising a polymerization product of at least one macromer as defined in claim 1 and, if appropriate, of at least one vinylic comonomer (a).

49. A polymer according to claim 48, in which the weight content of the macromer is in the range from 100 to 0.5%, based on the total weight of the polymer.

50. A polymer according to claim 48, in which comonomer (a) is absent.

51. A polymer according to claim 48, in which comonomer (a) is hydrophilic or hydrophobic or a mixture of both.

52. A polymer according to claim 48, in which comonomer (a) is chosen from C₁ -C₁₈ alkyl and C₃ -C₁₈ cycloalkyl acrylate and methacrylate, C₃ -C₁₈ alkylacrylamide and -methacrylamide, acrylonitrile, methacrylonitrile, vinyl C₁ -C₁₈ alkanoate, C₂ -C₁₈ alkene, C₂ -C₁₈ haloalkene, styrene, lower alkyl styrene, lower alkyl vinyl ether, C₂ -C₁₀ perfluoroalkyl acrylate and methacrylate or correspondingly partly fluorinated acrylate and methacrylate, C₃ -C₁₂ perfluoroalkyl-ethyl-thio carbonylaminoethyl acrylate and methacrylate, acryloxy- and methacryloxy-alkylsiloxane, N-vinylcarbazole and C₁ -C₁₂ alkyl ester of maleic acid, fumaric acid, itaconic acid, and mesaconic acid.

53. A polymer according to claim 48, in which comonomer (a) is chosen from hydroxyl-substituted lower alkyl acrylate and methacrylate, acrylamide, methacrylamide, lower alkylacrylamide and -methacrylamide, ethoxylated acrylate and methacrylate, hydroxyl-substituted lower alkylacrylamide and -methacrylamide, hydroxyl-substituted lower alkyl vinyl ether, sodium vinylsulfonate, sodium styrenesulfonate, 2-acrylamido-2-methylpropanesulfonic acid, N-vinylpyrrole, N-vinyl-2-pyrrolidone, 2-vinyloxazoline, 2-vinyl-4,4'"'"'-dialkyloxazolin-5-one, 2- and 4-vinylpyridine, vinylically unsaturated carboxylic acid having a total of 3 to 5 carbon atoms, amino-lower alkyl (where the term "amino" also includes quaternary ammonium), mono-lower alkylamino-lower alkyl and di-lower alkylamino-lower alkyl acrylate and methacrylate, and allyl alcohol.

54. A polymer according to claim 48, furthermore comprising at least one comonomer (b).

55. A polymer according to claim 54, in which comonomer (b) is chosen from allyl (meth)acrylate, lower alkylene glycol di(meth)acrylate, poly lower alkylene glycol di(meth)acrylate, lower alkylene di(meth)acrylate, divinyl ether, divinyl sulfone, di- or trivinylbenzene, tetramethylolpropane tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, bisphenol A di(meth)acrylate, methylenebis(meth)acrylamide, triallyl phthalate or diallyl phthalate.

58. A molding comprising a polymer according to claim 48.

59. A molding comprising a polymer according to claim 48, wherein the surface of the molding is plasma treated in the presence of a C₁ -C₆ alkane and a gas which is selected from the group consisting of nitrogen, argon, oxygen, and mixtures thereof.

60. A molding according to claim 58, which is a contact lens.

61. A molding according to claim 58, which is a soft contact lens having a water content of 1-40%, based on the total weight of the molding.

62. A molding according to claim 58, which is a flexible contact lens which is permeable to gas and has a low water content (RGP).

63. A method comprising polymerizing and shaping a macromer as defined in claim 1 for the production of a molding.

64. A method comprising polymerizing and shaping a macromer as defined in claim 1 for the production of a contact lens.

14. A macromer comprising at least one section of the formula (I) ##STR17## in which (a) is a polysiloxane segment;

(b) is a polyol segment derived from a mono-, di-, tri-, tetra-, oligo- or polysaccharide;

from a lactone of an aldonic or uronic;

or from glucuronic acid lactone, mannuronic acid lactone or iduronic acid lactone,

Z is a segment formed by a condensation reaction and is (c) or a group X₁, in which segment (c) is defined as X₂ --R--X₂, in which R is a bivalent radical of an organic compound having up to 20 C atoms and each X₂ independently of the other is a bivalent radical which contains at least one carbonyl group, and in which X₁ is defined as X₂, and in which

(d) is a radical of the formula (II)

space="preserve" listing-type="equation">X.sub.3 --L--(Y).sub.k --P.sub.1 (II)

in which P₁ is a group which can be polymerized by free radicals;

Y and X₃ independently of one another are a bivalent radical which contains at least one carbonyl group;

k is 0 or 1; and

L is a bond or a divalent radical having up to 20 C atoms of an organic compound.

16. A macromer of the formula (V) ##STR19## in which (a) is a polysiloxane segment containing q pendent ligands and in which

x is 1 or 2,

q has an average numerical value of 1-20, and in which the segments (b) in a macromer according to the formula (V) are linked in total (per molecule) with up to 20 polymerizable segments (d);

(b) is a polyol segment derived from a carbohydrate, carbohydrate monolactone, carbohydrate dilactone or a 1,3-polyol.

X₁ is a bivalent radical which contains at least one carbonyl group, and in which

(d) is a radical of the formula (II)

space="preserve" listing-type="equation">X.sub.3 --L--(Y).sub.k --P.sub.1 (II)

in which P₁ is a group which can be polymerized by free radicals;

Y and X₃ independently of one another are a bivalent radical which contains at least one carbonyl group;

k is 0 or 1; and

L is a bond or a divalent radical having up to 20 C atoms of an organic compound.

18. A macromer of the formula (VII) ##STR21## in which (a) is a polysiloxane segment, x is 0, 1 or 2, and

the average number of segments (d) per molecule of the formula (VII) is in the range from 2 to 5;

(b) is a polyol segment derived from a carbohydrate, carbohydrate monolactone, carbohydrate dilactone or a 1,3-polyol,

X₁ is a bivalent radical which contains at least one carbonyl group, and in which

(d) is a radical of the formula (II)

space="preserve" listing-type="equation">X.sub.3 --L--(Y).sub.k --P.sub.1 (II)

in which P₁ is a group which can be polymerized by free radicals;

Y and X₃ independently of one another are a bivalent radical which contains at least one carbonyl group;

k is 0 or 1; and

L is a bond or a divalent radical having up to 20 C atoms of an organic compound.

56. A Polymer which comprises the polymerization product of the following components in weight percent based on the total weight of the polymer:

(1) 25-45% of a macromer of formula IV in accordance to claim 18, wherein the variables are defined as follows;

a polysiloxane segment (a) is derived from a compound of the formula (III) ##STR28## in which 95-29% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are lower alkyl, 5-71% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are partly fluorinated alkyl, aminoalkyl or hydroxyalkyl, and n is an integer from 5 to 400;

a polyol segment (b) is derived from a carbohydrate, carbohydrate monolactone or carbohydrate dilactone;

(d) is a radical of the formula (II);

X₃ --L--(Y)_k --P₁, in which P₁ is alkenyl, X₃ is a urethane or urea group, Y is a carbonyl, ester or amide group, k is 0 or 1, and L is a bond or alkylene; and

X₁ is an ester, amide, urethane or urea group,

(2) 25-75% of a hydrophobic monomer, and

(3) 15-40% of a hydrophilic monomer.

35. A macromer of the formula (VIII)

View Dependent Claims (42, 57)

42. Macromer according to claim 35, wherein the variables are defined as follows:

a polysiloxane segment (a) is derived from a compound of the formula (III) ##STR24## in which 95-29% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are lower alkyl, 5-71% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are partly fluorinated alkyl, aminoalkyl or hydroxyalkyl, and n is an integer from 5 to 400;

polyol segment (b) is derived from a 1,3-polyol, carbohydrate, carbohydrate monolactone or carbohydrate dilactone, with the provisio that segment (b) is derived from a polyol which carries no lactone group if the group Z is a segment (c);

Z is a segment (c) or X₁, wherein X₁ is an ester, amide, urethane or urea group, and wherein segment (c) represents X₂ --R--X₂, in which R is alkylene, arylene, alkylenearylene or arylenealkylene having up to 14 carbon atoms, or a saturated bivalent cycloaliphatic group having 6 to 14 carbon atoms, and X₂ is an amide, urethane or urea group;

(B) is a segment (a) or a segment (b) with the above mentioned definitions; and

(d) is a radical of the formula (II);

X₃ --L--(Y)_k --P₁, which is up to 15 times terminally and/or pendently attached to a segment (b), and wherein P₁ is alkenyl, X₃ is a ester, amide, urethane or urea group, Y is a carbonyl, ester or amide group, k is 0 or 1, and L is a bond or alkylene.

57. Polymer which comprises the polymerization product of the following components in weight percent based on the total weight of the polymer:

(1) 25-45% of a macromer of formula (VII) according to the definitions of claim 35, wherein the variables are defined as follows;

a polysiloxane segment (a) is derived from a compound of the formula (III) in which 95-29% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are lower alkyl, 5-71% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are partly fluorinated alkyl, aminoalkyl or hydroxyalkyl, and n is an integer from 5 to 400;

a polyol segment (b) is derived from a polyol, carbohydrate, carbohydrate monolactone or carbohydrate dilactone, with the provisio that segment (b) is derived from a polyol which carries no lactone group if the group Z is a segment (c);

Z is a segment (c) or X₁, wherein X₁ is an ester, amide, urethane or urea group, and wherein segment (c) represents X₂ --R--X₂, in which R is alkylene, arylene, alkylenearylene or arylenealkylene having up to 14 carbon atoms, or a saturated bivalent cycloaliphatic group having 6 to 14 carbon atoms, and X₂ is an amide, urethane or urea group;

(B) is a segment (a) or a segment (b) with the above mentioned definitions; and

(d) is a radical of the formula (II);

X₃ --L--(Y)_k --P₁, which is up to 15 times terminally and/or pendently attached to a segment (b), and wherein P₁ is alkenyl, X₃ is a ester, amide, urethane or urea group, Y is a carbonyl, ester or amide group, k is 0 or 1, and L is a bond or alkylene,

(2) 25-75% of a hydrophobic monomer, and

(3) 15-40% of a hydrophilic monomer.

36. A macromer of the formula (IX)

41. Macromer of the formula (IV) ##STR22## in which (a) is a polysiloxane segment is derived from a compound of the formula ##STR23## in which 95-29% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are lower alkyl, 5-71% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are partly fluorinated alkyl, aminoalkyl or hydroxyalkyl, and n is an integer from 5 to 400;

the polyol segment (b) is derived from a carbohydrate, carbohydrate monolactone or carbohydrate dilactone;

(d) is a radical of the formula (II);

X₃ --L--(Y)_k --P₁, in which P₁ is alkenyl, X₃ is a urethane or urea group, Y is a carbonyl, ester or amide group, k is 0 or 1, and L is a bond or alkylene; and

X₁ is an ester, amide, urethane or urea group.

43. A process for the preparation of a macromer, which comprises first reacting a polysiloxane containing at least one primary amino- or hydroxyalkyl group with a carbohydrate lactone, an amide or ester bond being formed and a compound of the formula (XIIa) or (XIIb) being formed

View Dependent Claims (44, 45, 46, 47)

44. A process for the preparation of a macromer as defined in claim 43, which comprises reacting a polysiloxane (a) which contains terminal primary amino- or hydroxyalkyl groups with a carbohydrate dilactone to give linear structures of the formula (XIV)

45. A process for the preparation of a macromer as defined in claim 43, which comprises first reacting a polysiloxane (a) which contains terminal primary amino- or hydroxyalkyl groups with a bifunctional compound of the formula (XV)

46. A process for the preparation of a macromer as defined in claim 43, which comprises reacting a bifunctional compound of the formula (XV)

47. A process for the preparation of a macromer as defined in claim 43, which comprises reacting, in a first step, a carbohydrate lactone with a compound of the formula (XIII), the lactone function being retained, after which the intermediate is reacted with a polysiloxane containing at least one amino or hydroxyl group to give a compound of the formula (IV) or (V) ##STR27## in which q is 1 or 2, and x is 0, 1 or 2.