Polysiloxane-comprising perfluoroalkyl ethers and the preparation and use thereof

• US 5,945,498 A
• Filed: 12/22/1997
• Issued: 08/31/1999
• Est. Priority Date: 04/04/1995
• Status: Expired due to Term

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Domschke, Angelika, Lohmann, Dieter, Hopken, Jens
• Primary Examiner(s): MOORE, MARGARET G
• Application Number:
  US08/776,985
• Time in Patent Office: 617 Days
• Field of Search: 528/42, 528/26, 528/28, 528/29, 528/38, 526/279, 351/160 R, 264/1.36, 264/2.6, 523/107, 523/113, 428/421, 428/447, 623/5
• US Class Current: 528/42
• 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.
• CPC Class Codes: Y10T 428/3154 : Of fluorinated addition polymer from unsaturated monomers
• CPC Class Codes: Y10T 428/31544 : Addition polymer is perhalogenated
• CPC Class Codes: Y10T 428/31663 : As siloxane, silicone or silane

Abstract

The present invention describes a free radical polymerizable segmented macromonomer based on perfluoroelkyl ether, polysiloxane and divalent organic segments. This macromoner can be polymerized and used to form moldings, contact lenses, corneal implants and other biomedical articles.

Claims

1. A macromer of the formula (I)

View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68)

2. A macromer according to claim 1, in which the number of segments (b) in the polymer fragment Q is greater than or equal to the number of segments (a).

3. A macromer according to claim 1, in which the ratio between segments (a) and (b) in polymer fragment Q is 3:

4, 2;

3, 1;

2 or 1;

1.

4. A macromer according to claim 1, in which the mean molecular weight of the polymer fragment Q is in the range from about 1000 to about 20000.

5. A macromer according to claim 1, in which the total number of segments (a) and (b) in the polymer fragment Q is in the range from 2 to about 11.

6. A macromer according to claim 1, in which the smallest polymer fragment Q comprises, on stoichiometric average, one perfluoro segment (a), one siloxane segment (b) and one segment (c).

7. A macromer according to claim 1, in which the polymer fragment Q is terminated, on stoichiometric average, at each end by a siloxane segment (b).

8. A macromer according to claim 1, in which X₁ is --NHCONH--, --NHCOO-- or --OCONH--.

9. A macromer according to claim 1, in which the segment X₂ --R--X₂ is a radical derived from a diisocyanate, where each X₂, independently of the other, is --NHCONH--, --NHCOO or --OCONH--.

10. A macromer according to claim 1, in which Z is a bond, lower alkylene or --CONH-arylene, where the --CO-- moiety is linked to a CF₂ group.

11. A macromer according to claim 1, in which Z is lower alkylene.

12. A macromer according to claim 1, in which the indices x+y are a number in the range from 10 to 25.

13. A macromer according to claim 1, in which the ratio x:

y is in the range from 0.5 to 1.5.

14. A macromer according to claim 1, in which the free-radical-polymerizable group P₁ is alkenyl, alkenylaryl or alkenylarylenealkyl having up to 20 carbon atoms.

15. A macromer according to claim 1, in which P₁ is alkenyl or alkenylaryl having up to 12 carbon atoms.

16. A macromer according to claim 1, in which Y is --COO--, --OCO--, --NHCONH--, --NHCOO--, --OCONH--, --NHCO-- or --CONH--.

17. A macromer according to claim 1, in which the indices m and p are not simultaneously zero.

18. A macromer according to claim 1, in which L is alkylene, arylene, aiylenealkylene, alkylenearylene, alkylenearylenealkene or arylenealkylenearylene.

19. A macromer according to claim 1, in which L is alkylene or arylene having up to 12 carbon atoms.

20. A macromer according to claim 1, in which the divalent radical R is alkylene, arylene, alkylenearylene, arylenealkylene or arylenealkylenearylene having up to 20 carbon atoms or cycloalkylenealkylenecycloalkylene having 7 to 20 carbon atoms.

21. A macromer according to claim 1, in which R is alkylene, arylene, alkylenearylene, arylenealkylene or arylenealkylenearylene having up to 14 carbon atoms.

22. A macromer according to claim 1, in which R is alkylene, arylene, alkylenearylene or arylenealkylene having up to 14 carbon atoms.

23. A macromer according to claim 1, in which n is an integer from 5 to 70.

24. A macromer according to claim 1, in which 85-100% of the radicals R₁ R₂, R₃ and R₄, independently of one another, are lower alkyl having up to 8 carbon atoms.

25. A macromer according to claim 1, in which 0-15% of the radicals R₁, R₂, R₃ and R₄, independently of one another, are lower alkenyl, phenyl which is unsubstituted or substituted by lower alkyl or lower alkoxy, or cyano(lower alkyl).

26. A macromer according to claim 1, wherein P₁ is, independently of the other, lower alkenyl, Y is, independently of the other, --COO-- or --OCO--, L is independently of the other, lower alkylene, X₁ is, independently of the other, --NHCOO-- or --OCONH--, p and m are 1;

the polymer fragment Q has up to 3 segments (a), up to 4 segments (b) and up to 6 segments (c), wherein in segment (a) the sum of the indices x+y is in the range of 10-15, Z is lower alkylene and k is 0, wherein in segment (b) Alk is lower alkylene, the radicals R₁, R₂, R₃ and R₄ are each, independently of the others, lower alkyl and n is in the range of 14-28, and wherein in segment (c) R is alkylene or arylene having up to 14 carbon atoms or a saturated divalent cycloaliphatic group having 6-14 carbon atoms, and X₂ is --NHCOO-- or --OCONH--.

27. A macromer according to claim 1, wherein P₁ is, independently of the other, lower alkenyl, Y is, independently of the other, --COO-- or --OCO--, L is, independently of the other, lower alkylene, X₁ is, independently of the other, --NHCOO-- or --OCONH--, p and m are 1;

the polymer fragment Q has a segment (a), up to 2 segments (b) and up to 2 segments (c), wherein in segment (a) the sum of the indices x+y is in the range of 10-15, Z is lower alkylene and k is 0, wherein in segment (b) Alk is lower alkylene, the radicals R₁ R₂, R₃ and R₄ are each, independently of the others, lower alkyl and n is in the range of 14-28, and wherein in segment (c) R is alkylene or arylene having up to 14 carbon atoms or a saturated divalent cycloaliphatic group having 6-14 carbon atoms, and X₂ is --NHCOO or --OCONH--.

28. A macromer according to claim 1, wherein P₁ is, independently of the other, alkenyl having up to 4 carbon atoms, Y is, independently of the other, --COO-- or --OCO--, L is --OCONH--, p and m are 1;

the polymer fragment Q has a segment (a), 2 segments (b) 2 segments (c), wherein in segment (a) the sum of the indices x+y is in the range of 10-15, Z is lower alkylene and k is 0, wherein in segment (b) Alk is lower alkylene, the radicals R₁, R₂, R₃ and R₄ are each, independently of the others, lower alkyl and n is in the range of 14-28, and wherein in segment (c) R is alkylene or arylene having up to 14 carbon atoms or a saturated divalent cycloaliphatic group having 6-14 carbon atoms, and X₂ is --NHCOO-- or --OCONH--.

29. A macromer according to claim 1, wherein P₁ is, independently of the other, lower alkenyl, Y is, independently of the other, --COO-- or --OCO--, L is, independently of the other, lower alkylene, X₁ is, independently of the other, --NHCOO-- or --OCONH--, p and m are 1;

the polymer fragment Q has a segment (a), up to 2 segments (b) and up to 2 segments (c), wherein in segment (a) the sum of the indices x+y is in the range of 10-15, Z is lower alkylene and k is 0, wherein in segment (b) Alk is lower alkylene, the radicals R₁, R₂, R₃ and R₄ are each methyl and n is in the range of 14-28, and wherein in segment (c) R is alkylene or arylene having up to 14 carbon atoms or a saturated divalent cycloaliphatic group having 6-14 carbon atoms, and X₂ is --NHCOO-- or --OCONH--.

30. A macromer according to claim 1, wherein P₁ is, independently of the other, lower alkenyl having up to 4 C-atoms, Y is, independently of the other, --COO-- or --OCO--, L is, independently of the other, lower alkylene having up to 4 carbon atoms, X₁ is, independently of the other, --NHCOO-- or --OCONH--, p and m are 1;

the polymer fragment Q has a segment (a), up to 2 segments (b) and up to 2 segments (c), wherein in segment (a) the sum of the indices x+y is in the range of 10-15, Z is lower alkylene and k is 0, wherein in segment (b) Alk is lower alkylene having up to 4 carbon atoms, the radicals R₁, R₂, R₃ and R₄ are each, independently of the others, lower alkyl having up to 4 carbon atoms and n is in the range of 14-28, and wherein in segment (c) R is a saturated divalent cycloaliphatic group having 6-14 carbon atoms, and X₂ is --NHCOO-- or --OCONH--.

31. A process for the preparation of a macromer according to claim 1, wherein a perfluoropolyalkyl ether derivative of the formula (IV)

32. A polymer comprising a product of the polymerization of at least one compound of the formula (I) as defined in claim 1.

33. A polymer according to claim 32, wherein the proportion by weight of the compound of the formula (I) is in the range from 100 to 0.5%.

34. A polymer according to claim 32, which further comprises a vinylic comonomer (a).

35. A polymer according to claim 34, wherein the comonomer (a) is hydrophilic or hydrophobic or a mixture thereof.

36. A polymer according to claim 32, wherein the comonomer (a) is tristrimethylsilyloxysilylpropyl methacrylate, 2-hydroxyethyl methacrylate, dimethylaminoethyl methacrylate, tiimethylammonium 2-hydroxypropylmethacrylate hydrochloride, N,N-dimethylacrylamide or N-vinyl-2-pyrrolidone.

37. A crosslinked polymer comprising a product of the polymerization of at least one compound of the formula (1) as defined in claim 1 with at least one comonomer selected from the group consisting of a vinylic comonomer (a) and a polyunsaturated comonomer (b).

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

(1) 45-65% of a macromer according to claim 1,

(2) 15-30% of a hydrophobic monomer, and

(3) 10-35% of a hydrophilic monomer.

39. A polymer according to claim 38, comprising:

(1) 50-60% of a macromer according to claim 1,

(2) 20-25% of a hydrophobic monomer, and

(3) 15-30% of a hydrophlic monomer.

40. A polymer according to claim 38, comprising:

(1) 50-60% of a macromer of formula (1) according to claim 1, wherein P₁ is, independently of the other, lower alkenyl, Y is, independently of the other, --COO-- or --OCO--, L is, independently of the other, lower alkylene, X₁ is, independently of the other, --NHCOO-- or --OCONH--, p and m are 1;

the polymer fragment Q has up to 3 segments (a), up to 4 segments (b) and up to 6 segments (c), wherein in segment (a) the sum of the indices x+y is in the range of 10-15, Z is lower alkylene and k is 0, wherein in segment (b) Alk is lower alkylene, the radicals R₁, R₂, R₃ and R₄ are each independently of the others lower alkyl and n is in the range of 14-28, and wherein in segment (c) R is alkylene or arylene having up to 14 carbon atoms or a saturated divalent cycloaliphatic group having 6-14 carbon atoms, and X₂ is --NHCOO-- or --OCONH--,

(2) 20-25% of a hydrophobic monomer, and

(3) 15-30% of a hydrophilic monomer.

41. A molding comprising a polymer according to claim 32.

42. A moulding according to claim 41, which is a contact lens.

43. A moulding according to claim 42, which is an intraocular lens.

44. A moulding according to claim 41 wherein the surface of the moulding is plasma treated in the presence of a C₁ -C₆ alkane (a) and a gas (b) which is selected from the group consisting of nitrogen, argon, oxygen, and mixtures thereof.

45. A moulding which comprises the polymer of a polymerization product of the following components in weight percent based on the total weight of the polymer:

(1) 45-65% of a macromer according to formula (I) of claim 1 wherein P₁ is, independently of the other, lower alkenyl having up to 4 C-atoms, Y is, independently of the other, --COO-- or --OCO--, L is, independently of the other, lower alkylene having up to 4 carbon atoms, X₁ is, independently of the other, --NHCOO-- or --OCONH--, p and m are 1;

the polymer fragment Q has one segment (a), up to 2 segments (b) and up to 2 segments (c), wherein in segment (a) the sum of the indices x+y is in the range of 10-15, Z is lower alkylene and k is 0, wherein in segment (b) Alk is lower alkylene having up to 4 carbon atoms, the radicals R₁, R₂, R₃ and R₄ are, each independently of the others, lower alkyl having up to 4 carbon atoms and n is in the range of 14-28, and wherein in segment (c) R is a saturated divalent cycloaliphatic group having 6-14 carbon atoms, and X₂ is --NHCOO-- or --OCONH--,

(2) 15-30% of a hydrophobic monomer, and

(3) 10-35% of a hydrophilic monomer,

wherein the surface of said moulding is plasma treated in the presence of a methane and air.

46. A biomedical article comprising a polymer according to claim 32.

47. A corneal implant comprising a polymer according to claim 32.

48. A corneal implant according to claim 47 which can be used in surgical implantation on or in the cornea of a mammal, where said implant has an optical property in the region over the optical axis which is suitable for impairing visual acuity, furthermore has a porosity which is sufficient to allow components of tissue fluid having a molecular weight of greater than 10,000 daltons to pass through, with flow of tissue fluid from cells outside the implant to cells inside the implant being ensured, and where the porosity in the region over the optical axis is arranged to such an extent that flow of components of tissue fluid is possible, but ingrowth of ocular tissue is excluded.

49. A corneal implant according to claim 47, where the implant is coated with one or more components which promote growth of tissue in the vicinity of the implant and/or promote cell adhesion to the implant.

50. A corneal implant according to claim 47, where the porosity of the implant is provided by a multiplicity of pores whose size is sufficient to ensure flow of protein components of tissue fluid having a molecular weight of more than 10,000 daltons through the implant, but whose pore size excludes ingrowth of tissue.

51. A corneal implant according to claim 49, where the majority of the pores have a diameter of from 15 nanometers to 0.5 microns.

52. A cell-growth substrate comprising a polymer according to claim 32.

53. A medical implant comprising a polymer according to claim 32.

54. A macromer according to claim 4, in which the mean molecular weight of the polymer fragment Q is in the range from about 3000 to about 15,000.

55. A macromer according to claim 54, in which the mean molecular weight of the polymer fragment Q is in the range from about 5000 to about 12,000.

56. A macromer according to claim 5, in which the total number of segments (a) and (b) in the polymer fragment Q is in the range from 2 to about 9.

57. A macromer according to claim 56, in which the total number of segments (a) and (b) in the polymer fragment Q is in the range from 2 to about 7.

58. A macromer according to claim 12, in which the indices x+y are a number in the range from 10 to 15.

59. A macromer according to claim 13, in which the ratio x:

y is in the range from 0.7 to 1.1.

60. A macromer according to claim 15, in which P₁ is alkenyl or alkenylaryl having up to 8 carbon atoms.

61. A macromer according to claim 60, in which P₁ is alkenyl or alkenylaryl having up to 4 carbon atoms.

62. A macromer according to claim 23, in which n is an integer from 10 to 50.

63. A macromer according to claim 62, in which n is an integer from 14 to 28.

64. A macromer according to claim 24, in which 90-100% of the radicals R₁ R₂, R₃ and R₄, independently of one another, are lower alkyl having up to 4 carbon atoms.

65. A polymer according to claim 33, wherein the proportion by weight of the compound of the formula (I) is in the range from 80 to 10%.

66. A polymer according to claim 65, wherein the proportion by weight of the compound of the formula (I) is in the range from 70 to 30%.

67. An article having a surface coating which comprises a macromer of formula (I) of claim 1.

68. An article having a surface coating which comprises a polymer of claim 32.