U.S. patent application number 12/630147 was filed with the patent office on 2010-06-03 for biomedical devices containing internal wetting agents.
Invention is credited to Jonathan Patrick Adams, Azaam Alli, James D. Ford, Gregory A. Hill, Kevin P. McCabe, Frank F. Molock, JR., Kent Young.
Application Number | 20100133710 12/630147 |
Document ID | / |
Family ID | 26930087 |
Filed Date | 2010-06-03 |
United States Patent
Application |
20100133710 |
Kind Code |
A1 |
McCabe; Kevin P. ; et
al. |
June 3, 2010 |
BIOMEDICAL DEVICES CONTAINING INTERNAL WETTING AGENTS
Abstract
This invention includes a wettable biomedical device containing
a high molecular weight hydrophilic polymer and a
hydroxyl-functionalized silicone-containing monomer.
Inventors: |
McCabe; Kevin P.; (St.
Augustine, FL) ; Molock, JR.; Frank F.; (Orange Park,
FL) ; Young; Kent; (Jacksonville, FL) ; Hill;
Gregory A.; (Atlantic Beach, FL) ; Ford; James
D.; (Orange Park, FL) ; Alli; Azaam;
(Jacksonville, FL) ; Adams; Jonathan Patrick;
(Jacksonville, FL) |
Correspondence
Address: |
PHILIP S. JOHNSON;JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Family ID: |
26930087 |
Appl. No.: |
12/630147 |
Filed: |
December 3, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11223464 |
Sep 9, 2005 |
7649058 |
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12630147 |
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10236762 |
Sep 6, 2002 |
7052131 |
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11223464 |
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60318536 |
Sep 10, 2001 |
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Current U.S.
Class: |
264/1.36 ;
264/1.1; 351/159.33; 522/172; 525/418; 525/420; 525/451; 525/452;
525/474 |
Current CPC
Class: |
A61L 27/52 20130101;
A61L 27/18 20130101; A61L 27/26 20130101; C08L 83/04 20130101; C08L
83/04 20130101; A61L 27/18 20130101; A61L 27/26 20130101; G02B
1/043 20130101 |
Class at
Publication: |
264/1.36 ;
525/474; 525/452; 525/420; 525/451; 525/418; 522/172; 264/1.1;
351/160.H |
International
Class: |
G02B 1/12 20060101
G02B001/12; C08G 77/04 20060101 C08G077/04; C08G 18/61 20060101
C08G018/61; C08G 69/42 20060101 C08G069/42; C08G 63/91 20060101
C08G063/91; C08F 2/46 20060101 C08F002/46; B29D 11/00 20060101
B29D011/00; G02C 7/04 20060101 G02C007/04 |
Claims
1. A wettable silicone hydrogel comprising the reaction product of
at least one siloxane containing macromer; at least one high
molecular weight hydrophilic polymer; and at least one
compatibilizing component.
2. The hydrogel of claim 1 wherein said siloxane containing
macromer is present in an amount between about 5% to about 50%.
3. The hydrogel of claim 1 wherein the siloxane containing macromer
or prepolymer is present in an amount between about 10% to about
50%.
4. The hydrogel of claim 1 wherein the siloxane containing macromer
or prepolymer is present in an amount between about 15% to about
45%.
5. The hydrogel of claim 1 wherein said at least on siloxane
containing macromer comprises at least one siloxane group, and at
least one second group selected from the group consisting of
urethane groups, alkylene groups, alkylene oxide groups,
polyoxyalkalene groups, arylene groups, alkyl esters, amide groups,
carbamate groups, perfluoroalkoxy groups, isocyanate groups,
combinations thereof.
6. The hydrogel of claim 5 wherein said at least one siloxane
containing macromers is formed via polymerizing said siloxane group
with at least one acrylic or methacrylic compound.
7. The hydrogel of claim 5 wherein said at least one siloxane
containing macromer is selected from the group consisting of
methacrylate functionalized, silicone-fluoroether urethane
macromers, methacrylate functionalized, silicone urethane
macromers, styrene functionalized prepolymers of hydroxyl
functional methacrylates and silicone methacrylates and vinyl
carbamate functionalized polydimethylsiloxane
8. The hydrogel of claim 1 comprising about 1% to about 15% high
molecular weight hydrophilic polymer.
9. The hydrogel of claim 1 comprising about 3% to about 15% high
molecular weight hydrophilic polymer.
10. The hydrogel of claim 1 comprising about 5% to about 12% high
molecular weight hydrophilic polymer.
11. The silicone hydrogel of claim 14 wherein said hydrophilic
polymer is selected from the group consisting of polyamides,
polylactones, polyimides, polylactams, functionalized polyamides,
functionalized polylactones, functionalized polyimides,
functionalized polylactams, and mixtures thereof.
12. The silicone hydrogel of claim 14 wherein said hydrophilic
polymer is selected from the group consisting of poly-N-vinyl
pyrrolidone, poly-N-vinyl-2-piperidone, poly-N-vinyl-2-caprolactam,
poly-N-vinyl-3-methyl-2- caprolactam,
poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-
piperidone, poly-N-vinyl-4-methyl-2-caprolactam,
poly-N-vinyl-3-ethyl-2- pyrrolidone, and
poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole,
poly-N-N-dimethylacrylamide, polyvinyl alcohol, polyacrylic acid,
polyethylene oxide, poly 2 ethyl oxazoline, heparin
polysaccharides, polysaccharides, mixtures and copolymers
thereof
13. The hydrogel of claim 1, wherein the high molecular weight
hydrophilic polymer is poly-N-vinylpyrrolidone.
14. The silicone hydrogel of claim 1 wherein said compatibilzing
component is a compound of Formula I or II ##STR00014## wherein: n
is an integer between 3 and 35 R.sup.1 is hydrogen, C.sub.1-6alkyl,
R.sup.2,R.sup.3, and R.sup.4, are independently, C.sub.1-6alkyl,
triC.sub.1-6alkylsiloxy, phenyl, naphthyl, substituted
C.sub.1-6alkyl, substituted phenyl, or substituted naphthyl where
the alkyl substitutents are selected from one or more members of
the group consisting of C.sub.1-6alkoxycarbonyl, C.sub.1-6alkyl,
C.sub.1-6alkoxy, amide, halogen, hydroxyl, carboxyl,
C.sub.1-6alkylcarbonyl and formyl, and where the aromatic
substitutents are selected from one or more members of the group
consisting of C.sub.1-6alkoxycarbonyl, C.sub.1-6alkyl,
C.sub.1-6alkoxy, amide, halogen, hydroxyl, carboxyl,
C.sub.1-6alkylcarbonyl and formyl; R.sup.5 is a hydroxyl, an alkyl
group containing one or more hydroxyl groups, or
(CH.sub.2(CR.sup.9R.sup.10).sub.yO).sub.x)--R.sup.11 wherein y is 1
to 5, preferably 1 to 3, x is an integer of 1 to 100, preferably 2
to 90 and more preferably 10 to 25; R.sup.9-R.sup.11 are
independently selected from H, alkyl having up to 10 carbon atoms
and alkyls having up to 10 carbon atoms substituted with at least
one polar functional group; R.sup.6 is a divalent group comprising
up to 20 carbon atoms; R.sup.7 is a monovalent group that can
undergo free radicals or cationic polymerization, comprising up to
20 carbon atoms, and R8 is is a divalent or trivalent group
comprising up to 20 carbon atoms.
15. The silicone hydrogel of claim 1 wherein said
hydroxyl-functionalized silicone-containing monomer is selected
from the group consisting of 2-propenoic acid,
2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[trimethylsilyl)oxy]disilo-
xanyl]propoxy]propyl ester,
(3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane,
(2-methacryloxy-3-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane
and mixtures thereof.
16. The hydrogel of claim 1 wherein said compatibilizing component
comprises at least one compound of Formula III:
IWA-HB-[IWA-HB].sub.x-IWA Wherein x is 1 to 10; IWA is a
difunctional hydrophilic polymer having a number average molecular
weight of between about 1000 and about 50,000 Daltons; and HB is a
difunctional moeity comprising at least one N which is capable of
hydrogen bonding.
17. The hydrogel of claim 16 wherein said IWA is derived from
{acute over (.alpha.)},.omega.-hydroxyl terminated PVP and {acute
over (.alpha.)},.omega.-hydroxyl terminated polyoxyalkylene
glycols.
18. The hydrogel of claim 16 wherein HB is a difunctional group
selected from the group consisting of amides, imides, carbamates
ureas, and combinations thereof.
19. The hydrogel of claim 1 wherein said compatibilizing component
is present in an amount between about 5 and about 90 weight %.
20. The hydrogel of claim 1 further comprising at least one oxygen
permeable component in addition to said siloxane containing
macromer or prepolymer.
21. The hydrogel of claim 20 wherein said oxygen permeable
component is selected from the group consisting of amide analogs of
3-methacryloxypropyltris(trimethylsiloxy)silane; siloxane vinyl
carbamate analogs, siloxane vinyl carbonate analogs, and siloxane
containing monomers, combinations and oligomers thereof.
22. The hydrogel claim 20 wherein said oxygen permeable component
is selected from the group consisting of
3-methacryloxypropyltris(trimethylsiloxy)silane,
monomethacryloxypropyl terminated polydimethylsiloxanes,
polydimethylsiloxanes,
3-methacryloxypropylbis(trimethylsiloxy)methylsilane,
methacryloxypropylpentamethyl disiloxane and combinations
thereof.
23. The hydrogel of claim.20 wherein said oxygen permeable
component is present in an amount of 0 to about 80 weight %.
24. The hydrogel of 20 wherein said oxygen permeable component is
present in an amount of about 5 to about 60%.
25. The hydrogel of claim 20 wherein said oxygen permeable
component is present in an amount of about 10 to about 40%.
26. The hydrogel of claim 1 further comprising at least one
hydrophilic monomer.
27. The hydrogel claim 26 wherein said at least one hydrophilic
monomer comprises at least one acrylic group, vinyl group or a
combination thereof.
28. The hydrogel of claim 27 wherein said acrylic group has the
formula CH.sub.2.dbd.CRCOX, where R is hydrogen or C.sub.1-6alkyl
and X is O or N.
29. The hydrogel of claim 26 wherein said at least one hydrophilic
monomer is selected from the group consisting of
N,N-dimethylacrylamide, 2-hydroxyethyl methacrylate, glycerol
methacrylate, 2-hydroxyethyl methacrylamide, polyethyleneglycol
monomethacrylate, methacrylic acid, acrylic acid, N-vinyl
pyrrolidone, N-vinyl-N-methyl acetamide, N-vinyl-N-ethyl acetamide,
N-vinyl-N-ethyl formamide, N-vinyl formamide, hydrophilic vinyl
carbonate monomers, vinyl carbamate monomers, hydrophilic oxazolone
monomers, polydextran and copolymers and combinations thereof.
30. The hydrogel of claim 26 wherein said at least one hydrophilic
monomer comprises at least one polyoxyethylene polyols having one
or more of the terminal hydroxyl groups replaced with a functional
group containing a polymerizable double bond.
31. The hydrogel of claim 26 wherein said at least one hydrophilic
monomer is selected from the group consisting of polyethylene
glycol, ethoxylated alkyl glucoside, and polyethylene polyols
having one or more terminal polymerizable olefinic groups bonded to
the polyethylene polyol.
32. The hydrogel of claim 26 wherein said at least one hydrophilic
monomer is selected from the group consisting of
N,N-dimethylacrylamide, 2-hydroxyethyl methacrylate, glycerol
methacrylate, 2-hydroxyethyl methacrylamide, N-vinylpyrrolidone,
polyethyleneglycol monomethacrylate, methacrylic acid, acrylic acid
and combinations thereof.
33. The hydrogel of claim 26 wherein said at least one hydrophilic
monomer comprises N,N-dimethylacrylamide.
34. The hydrogel of claim 26 wherein said at least one hydrophilic
monomer is present in amounts of about 0 to about 70 weight %.
35. The hydrogel of claim 26 wherein said at least one hydrophilic
monomer is present in amounts of about 5 to about 60 weight %.
36. The hydrogel of claim 26 wherein said at least one hydrophilic
monomer is present in amounts of about 10 to 50 weight %.
37. The hydrogel of claim 1 comprising about 1 to about 15 weight %
high molecular weight hydrophilic polymer and about 5 to about 90
weight % hydroxyl-functionalized silicone-containing monomer.
38. The hydrogel of claims 1 comprising about 1% to about 15% high
molecular weight hydrophilic polymer; about 5 to about 90 weight %
compatibilizing component; about 5 to about 50 weight % said
siloxane containing macromer, 0 to about 80 weight % siloxane
containing monomer and 0 to about 70 weight % hydrophilic
monomer.
39. The hydrogel of claim 1 comprising about 3% to about 15% high
molecular weight hydrophilic polymer; about 10 to about 80 weight %
compatibilizing component; about 10 to about 50 weight % said
siloxane containing macromer or prepolymer, 5 to about 60 weight %
siloxane containing momoner and 5 to about 60 weight % hydrophilic
monomer.
40. The hydrogel of claim 1 comprising about 5% to about 12% high
molecular weight hydrophilic polymer; about 15 to about 55 weight %
compatibilizing component; about 15 to about 45 weight % said
siloxane containing macromer, 10 to about 40 weight % oxygen
permeable component and 10 to about 50 weight % hydrophilic
monomer.
41. A silicone hydrogel contact lens comprising the hydrogel of
claim 1 and wherein said contact lens is not surface modified.
42. The lens of of claim 41, wherein the contact lens is a soft
contact lens.
43. The lens of claim 41 wherein said lens has an advancing dynamic
contact angle of less than about 70.degree..
44. The lens of claim 41 wherein said lens has an advancing dynamic
contact angle of less than about 60.degree..
45. The lens of claim 41 wherein said lens, after about one day of
wear, has a tear film break up time of at least about 7
seconds.
46. The lens of claim 41 wherein said lens further comprises a
modulus of less than about 90 psi.
47. The lens of claims 41 wherein said lens further comprises a
water content between about 10 and about 60%.
48. The hydrogel of claim 1 wherein said high molecular weight
hydrophilic polymer is present in an amount sufficient to provide
an article formed from said hydrogel with an advancing dynamic
contact angle which is at least about 10% lower than a hydrogel
without said hydrophilic polymer.
49. The hydrogel of claim 1 wherein said hydrogel is an
interpenetrating network or a semi-interpenetrating network.
50. A method comprising the steps of (a) mixing at least one
diluent which is water soluble at processing conditions and
reactive components comprising at least one high molecular weight
hydrophilic polymer, at least one siloxane containing macromer and
an effective amount of at least one compatibilizing component to
form a reaction mixture and (b) curing the product of step (a) to
form a biomedical device; (c) removing said biomedical device from
a mold in which said biomedical device was cured and (d) hydrating
said biomedical device, wherein both steps (c) and (d) are
performed in aqueous solutions which comprise water as a
substantial component.
51. The method of claim 50 wherein said biomedical device comprises
an ophthalmic device.
52. The method of claim 50 wherein said ophthalmic device is a
silicone hydrogel contact lens.
53. (canceled)
54. The method of claim 50 wherein said diluent is selected from
the group consisting of ethers, esters, alkanes, alkyl halides,
silanes, amides, alcohols and mixtures thereof.
55. The method of claim 50 wherein said diluent selected from the
group consisting amides, alcohols and mixtures thereof.
56. The method of claim 50 wherein said diluent selecting the group
consisting of tetrahydrofuran, ethyl acetate, methyl lactate,
i-propyl lactate, ethylene chloride, octamethylcyclotetrasiloxane,
dimethyl formamide, dimethyl acetamide, dimethyl propionamide, N
methyl pyrrolidinone mixtures thereof and mixtures of any of the
foregoing with at least one alcohol.
57. The method of claim 50 wherein said diluent comprises at least
one alcohol having at least 4 carbon atoms.
58. The method of claim 50 wherein said diluent comprises at least
one alcohol having at least 5 carbons atoms.
59. The method of claim 50 wherein said diluents are inert and
easily displaceable with water.
60. The method of claim 50 wherein said diluent comprises at least
one alcohol selected from the group consisting of tert-butanol,
tert-amyl alcohol, 2-butanol, 2-methyl-2-pentanol,
2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 3-ethyl-3-pentanol,
3,7-dimethyl-3-octanol and mixtures thereof.
61. The method of claim 50 wherein said diluent is selected from
the group consisting of hexanol, heptanol, octanol, nonanol,
decanol, tert-butyl alcohol, 3-methyl-3-pentanol, isopropanol, t
amyl alcohol, ethyl lactate, methyl lactate, i-propyl lactate,
3,7-dimethyl-3-octanol, dimethyl formamide, dimethyl acetamide,
dimethyl propionamide, N methyl pyrrolidinone and mixtures
thereof.
62. The method of claim 50 wherein said diluent is selected from
the group consisting of 1-ethoxy-2-propanol, 1-methyl-2-propanol,
t-amyl alcohol, tripropylene glycol methyl ether, isopropanol,
1-methyl-2-pyrrolidone, N,N-dimethylpropionamide, ethyl lactate,
dipropylene glycol methyl ether and mixtures thereof.
63. The method of claim 50 wherein said diluent is present in an
amount less than about 40 weight % based upon the reaction
mixture.
64. The method of claim 50 wherein said diluent is present in an
amount between about 10 and about 30 weight % based upon the
reaction mixture.
65. (canceled)
66. The method of claim 5350 wherein said curing is conducted via
heat, exposure to radiation or a combination thereof and said
reaction mixture further comprises at least one initiator.
67. The method of claim 66 wherein said curing is conducted via
irradiation comprises ionizing and/or actinic radiation and said
initiator comprises at least one photoinitiator.
68. The method of claim 67 wherein said radiation comprises light
having a wavelength of about 150 to about 800 nm and said initiator
is selected from the group consisting of aromatic alpha-hydroxy
ketones, alkoxydoxybenzoins, acetophenones, acyl phosphine oxides,
mixtures of tertiary amines and diketones, and mixtures
thereof.
69. The method of claim 67 wherein said initiator is selected from
the group consisting of 1-hydroxycyclohexyl phenyl ketone,
2-hydroxy-2-methyl-1-phenyl-propan-1-one,
bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide,
bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide,
2,4,6-trimethylbenzyldiphenyl phosphine oxide and
2,4,6-trimethylbenzyoyl diphenylphosphine oxide, benzoin methyl
ester, combinations of camphorquinone and ethyl
4-(N,N-dimethylamino)benzoate and mixtures thereof.
70. The method of claim 67 wherein said initiator is present in the
reaction mixture in amounts from about 0.1 to about 2 weight
percent based upon said reactive components.
71. The method of claim 67 wherein said curing is conducted via
visible light irradiation.
72. The method of claim 71 wherein said initiator comprises
1-hydroxycyclohexyl phenyl ketone,
bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide and
mixtures thereof.
73. The method of claim 71 wherein said initiator comprises
bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide.
74. The method of claims 67 wherein said reactive components
further comprises at least one UV absorbing compound.
75. The method of claim 71 wherein said curing step is conducted at
a cure intensity between about 0.1 and about 6 mW/cm.sup.2.
76. The method of claim 71 wherein said curing step is conducted at
a cure intensity of between about. 0.2 mW/cm.sup.2 to about 3
mW/cm.sup.2.
77. The method of claims 75 wherein said curing step further
comprises a cure time of at least about 1 minute.
78. The method of claims 75 wherein said curing step further
comprises a cure time of between about 1 and about 60 minutes.
79. The method of claim 75 wherein said curing step further
comprises a cure time of between about 1 and about 30 minutes.
80. The method of claim 75 wherein said curing step is conducted at
a temperature greater than about 25.degree. C.
81. The method of claim 75 wherein said curing step is conducted at
a temperature between about 25.degree. C. and 70.degree. C.
82. The method of claim 75 wherein said curing step is conduct at a
temperature between about 40.degree. C. and 70.degree. C.
83. The method of claim 5350 wherein said reaction mixture is cured
in a mold and said method further comprises the step deblocking
said ophthalmic device from said mold.
84. The method of claim 83 wherein said reaction mixture further
comprises at least one low molecular weight hydrophilic
polymer.
85. The method of claim 84 wherein said low molecular weight
hydrophilic polymer has a number average molecular weight of less
than about 40,000 Daltons.
86. The method of claim 84 wherein said low molecular weight
hydrophilic polymer has a number average molecular weight of less
than about 20,000 Daltons.
87. The method of claim 84 wherein the low molecular weight polymer
is selected from the group consisting of water soluble polyamides,
lactams and polyethylene glycols, and mixtures thereof.
88. The method of claim 84 wherein the low molecular weight polymer
is selected from the group consisting poly-vinylpyrrolidone,
polyethylene glycols, poly 2 ethyl-2-oxazoline and mixtures
thereof.
89. The method of claim 84 wherein the low molecular weight
hydrophilic polymer is present in amounts up to about 20 weight %
based upon the reaction mixture.
90. The method of claim 84 wherein the low molecular weight
hydrophilic polymer is present in amounts between about 5 and about
20 weight % based upon the reaction mixture.
91. The method of claim 84 wherein said deblocking is conducted
using an aqueous solution.
92. The method of claim 84 wherein said aqueous solution further
comprises at least one surfactant.
93. The method of claim 92 wherein said surfactant comprises at
least one non-ionic surfactant.
94. The method of claim 92 wherein said surfactant comprises
TWEEN.RTM., or DOE120.
95. The method of claim 92 wherein said surfactant is present in
amounts up to about 10,000 ppm.
96. The method of claim 92 wherein said surfactant is present in
amounts between about 100 and about 1200 ppm.
97. The method of claim 83 wherein said aqueous solution comprises
at least one organic solvent.
98. The method of claim 83 wherein said deblocking is conducted at
a temperature between about ambient and about 100.degree. C.
99. The method of claim 83 wherein said deblocking is conducted at
a temperature between about 70.degree. C. and about 95.degree.
C.
100. The method of claim 83 wherein said deblocking is conducted
using agitation.
101. The method of claim 83 wherein said agitation comprises
sonication.
102. A method comprising the steps of (a) mixing reactive
components comprising a high molecular weight hydrophilic polymer
and an effective amount of a compatibilizing component and (b)
curing the product of step (a) at or above a minimum gel time, to
form a wettable biomedical device.
103. The method of claim 102 wherein said device is a ophthalmic
lens.
104. The method of claim 103 wherein said device is a contact
lens.
105. The method of claim 103 wherein said lens comprises an
advancing dynamic contact angle of about 80.degree. or less.
106. The method of claim 103 wherein said lens comprises an
advancing dynamic contact angle of about 70.degree. or less.
107. The method of claim 103 wherein said lens comprises a tear
film break up time of at least about 7 seconds.
108. The method of claim 103 wherein said reactive components
further comprises at least one initiator
109. The method of claim 108 wherein said cure is conducted via
irradiation and said conditions comprise an initiator concentration
and cure intensity effective to provide said minimum gel time.
110. The method of claim 109 wherein said initiator is present in
an amount up to about 1% based upon all reactive components.
111. The method of claim 109 wherein said initiator is present in
an amount less than about 0.5% based upon all reactive
components.
112. The method of claim 109 wherein said cure is conducted via
irradiation at an intensity of less than about 5 mW/cm.sup.2.
113. The method of claim 109 wherein said gel time is at least
about 30 seconds.
114. The method of claim 109 wherein said gel time is at least
about 35 seconds.
115. The method of claim 102 wherein said compatibilizing component
is not a hydroxyl functionalized macromer made by group transfer
polymerization.
116. The method of claim 102 wherein said reactive components
further comprise at least one macromer.
117. The method of claim 50 wherein said compatibilizing component
is not a hydroxyl functionalized macromer made by group transfer
polymerization.
118. A method for improving the wettability of an ophthalmic device
formed from a reaction mixture comprising adding at least one high
molecular hydrophilic weight polymer and a compatibilizing
effective amount of at least one compatibilizing component to said
reaction mixture, wherein said compatibilizing component is not a
styrene functionalized prepolymer made from hydroxyl functional
methacrylates.
119. The method of claim 118 wherein said compatibilizing component
has a compatibility index of greater than about 0.5.
120. The method of claim 118 wherein said compatibilizing component
has a compatibility index of greater than about 1.
121. The method of claim 118 wherein said compatibilizing component
comprises at least one siloxane group.
122. The method of claim 121 wherein said compatibilizing component
further comprises hydroxyl functionality and has a Si to OH ratio
of less than about 15:1.
123. The method of claim 121 wherein said compatibilizing component
has a Si to OH ratio of between about 1:1 to about 10:1.
124. An ophthalmic lens comprising a silicone hydrogel which has,
without surface treatment, a tear film break up time of at least
about 7 seconds
125. A silicone hydrogel contact lens comprising at least one
oxygen permeable component, at least one compatibilizing component
and an amount of high molecular weight hydrophilic polymer
sufficient to provide said device, without a surface treatment,
with tear film break up time after about one day of wear of at
least about 7 seconds.
126. A device comprising a silicone hydrogel contact lens which is
substantially free from surface deposition without surface
modification.
Description
RELATED PATENT APPLICATIONS
[0001] This patent application claims priority of a provisional
application, U.S. Ser. No. 60/318,536 which was filed on Sep. 10,
2001.
FIELD OF THE INVENTION
[0002] This invention relates to silicone hydrogels that contain
internal wetting agents, as well as methods for their production
and use.
BACKGROUND OF THE INVENTION
[0003] Contact lenses have been used commercially to improve vision
since at least the 1950s. The first contact lenses were made of
hard materials and as such were somewhat uncomfortable to users.
Modern lenses have been developed that are made of softer
materials, typically hydrogels and particularly silicone hydrogels.
Silicone hydrogels are water-swollen polymer networks that have
high oxygen permeability and surfaces that are more hydrophobic
than hydrophilic. These lenses provide a good level of comfort to
many lens wearers, but there are some users who experience
discomfort and excessive ocular deposits leading to reduced visual
acuity when using these lenses. This discomfort and deposits has
been attributed to the hydrophobic character of the surfaces of
lenses and the interaction of those surfaces with the protein,
lipids and mucin and the hydrophilic surface of the eye.
[0004] Others have tried to alleviate this problem by coating the
surface of silicone hydrogel contact lenses with hydrophilic
coatings. For example, it has been disclosed that silicone hydrogel
lenses can be made more compatible with ocular surfaces by applying
plasma coatings to the lens surface. However, uncoated silicone
hydrogel lenses having low incidences of surface deposits have not
been disclosed.
[0005] Incorporating internal hydrophilic agents (or wetting
agents) into a macromer containing reaction mixture has been
disclosed. However, not all silicone containing macromers display
compatibility with hydrophilic polymers. Modifying the surface of a
polymeric article by adding polymerizable surfactants to a monomer
mix used to form the article has also been disclosed. However,
lasting in vivo improvements in wettability and reductions in
surface deposits are not likely.
[0006] Polyvinylpyrrolidone (PVP) or poly-2-ethyl-2-oxazoline have
been added to a hydrogel composition to form an interpenetrating
network which shows a low degree of surface friction, a low
dehydration rate and a high degree of biodeposit resistance.
However, the hydrogel formulations disclosed are conventional
hydrogels and there is no disclosure on how to incorporate
hydrophobic components, such as siloxane monomers, without losing
monomer compatibility.
[0007] While it may be possible to incorporate high molecular
weight polymers as internal wetting agents into silicone hydrogel
lenses, such polymers are difficult to solubilize in reaction
mixtures which contain silicones. In order to solubilize these
wetting agents, silicone macromers or other prepolymers must be
used. These silicone macromers or prepolymers must be prepared in a
separate step and then subsequently mixed with the remaining
ingredients of the silicone hydrogel formulation. This additional
step (or steps) increases the cost and the time it takes to produce
these lenses.
[0008] Therefore it would be advantageous to find a lens
formulation that does not require the use of surface treatment to
provide on eye wettability and resistance to surface
depositions.
SUMMARY OF THE INVENTION
[0009] The present invention relates to a wettable silicone
hydrogel comprising the reaction product of at least one siloxane
containing macromer; at least one high molecular weight hydrophilic
polymer; and at least one compatibilizing component.
[0010] The present invention further relates to a ethod comprising
the steps of (a) mixing reactive components comprising at least one
high molecular weight hydrophilic polymer, at least one siloxane
containing macromer and an effective amount of at least one
compatibilizing component and (b) curing the product of step (a) to
form a biomedical device.
[0011] The present invention further comprises a method comprising
the steps of (a) mixing reactive components comprising a high
molecular weight hydrophilic polymer and an effective amount of a
compatibilizing component and (b) curing the product of step (a) at
or above a minimum gel time, to form a wettable biomedical
device.
[0012] The present invention yet further relates to an ophthalmic
lens comprising a silicone hydrogel which has, without surface
treatment, a tear film break up time of at least about 7
seconds
[0013] The present invention still further relates to a silicone
hydrogel contact lens comprising at least one oxygen permeable
component, at least one compatibilizing component and an amount of
high molecular weight hydrophilic polymer sufficient to provide
said device, without a surface treatment, with tear film break up
time after about one day of wear of at least about 7 seconds.
[0014] A device comprising a silicone hydrogel contact lens which
is substantially free from surface deposition without surface
modification.
DETAILED DESCRIPTION OF THE INVENTION
[0015] A biomedical device formed from a reaction mixture
comprising, consisting essentially of, or consisting of a silicone
containing macromer, at least one high molecular weight hydrophilic
polymer and a compatibilizing amount of a compatibilizing
component.
[0016] It has been surprisingly found that biomedical devices, and
particularly ophthalmic devices having exceptional in vivo or
clinical wettability, without surface modification may be made by
including an effective amount of a high molecular weight
hydrophilic polymer and a compatibilizing amount of a
compatibilizing component in a silicone hydrogel formulation. By
exceptional wettability we mean a decrease in advancing dynamic
contact angle of at least about 10% and preferably at least about
20% in some embodiments at least about 50% as compared to a similar
formulation without any hydrophilic polymer. Prior to the present
invention ophthalmic devices formed from silicone hydrogels either
had to be surface modified to provide clinical wettability or be
formed from at least one silicone containing macromer having
hydroxyl functionality.
[0017] As used herein, a "biomedical device" is any article that is
designed to be used while either in or on mammalian tissues or
fluid and preferably on or in human tissues or fluid. Examples of
these devices include but are not limited to catheters, implants,
stents, and ophthalmic devices such as intraocular lenses and
contact lenses. The preferred biomedical devices are ophthalmic
devices, particularly contact lenses, most particularly contact
lenses made from silicone hydrogels.
[0018] As used herein, the terms "lens" and "opthalmic device"
refer to devices that reside in or on the eye. These devices can
provide optical correction, wound care, drug delivery, diagnostic
functionality or cosmetic enhancement or effect or a combination of
these properties. The term lens includes but is not limited to soft
contact lenses, hard contact lenses, intraocular lenses, overlay
lenses, ocular inserts, and optical inserts.
[0019] As used herein the term "monomer" is a compound containing
at least one polymerizable group and an average molecular weight of
about less than 2000 Daltons, as measure via gel permeation
chromatography refractive index detection. Thus, monomers, include
dimers and in some cases oligomers, including oligomers made from
more than one monomeric unit.
[0020] As used herein, the phrase "without a surface treatment"
means that the exterior surfaces of the devices of the present
invention are not separately treated to improve the wettability of
the device. Treatments which may be foregone because of the present
invention include, plasma treatments, grafting, coating and the
like. However, coatings which provide properties other than
improved wettability, such as, but not limited to antimicrobial
coatings may be applied to devices of the present invention.
[0021] Various molecular weight ranges are disclosed herein. For
compounds having discrete molecular structures, the molecular
weights reported herein are calculated based upon the molecular
formula and reported in gm/mol. For polymers molecular weights
(number average) are measured via gel permeation chromatography
refractive index detection and reported in Daltons or are measured
via kinematic viscosity measurements, as described in Encyclopedia
of Polymer Science and Engineering, N-Vinyl Amide Polymers, Second
edition, Vol 17, pgs. 198-257, John Wiley & Sons Inc. and
reported in K-values.
[0022] High Molecular Weight Hydrophilic Polymer
[0023] As used herein, "high molecular weight hydrophilic polymer"
refers to substances having a weight average molecular weight of no
less than about 100,000 Daltons, wherein said substances upon
incorporation to silicone hydrogel formulations, improve the
wettability of the cured silicone hydrogels. The preferred weight
average molecular weight of these high molecular weight hydrophilic
polymers is greater than about 150,000 Daltons; more preferably
between about 150,000 to about 2,000,000 Daltons, more preferably
still between about 300,000 to about 1,800,000 Daltons, most
preferably about 500,000 to about 1,500,000 Daltons (all weight
average molecular weight).
[0024] Alternatively, the molecular weight of hydrophilic polymers
of the invention can be also expressed by the K-value, based on
kinematic viscosity measurements, as described in Encyclopedia of
Polymer Science and Engineering, N-Vinyl Amide Polymers, Second
edition, Vol 17, pgs. 198-257, John Wiley & Sons Inc. When
expressed in this manner, hydrophilic monomers having K-values of
greater than about 46 and preferably between about 46 and about
150. The high molecular weight hydrophilic polymers are present in
the formulations of these devices in an amount sufficient to
provide contact lenses, which without surface modification remain
substantially free from surface depositions during use. Typical use
periods include at least about 8 hours, and preferably worn several
days in a row, and more preferably for 24 hours or more without
removal. Substantially free from surface deposition means that,
when viewed with a slit lamp, at least about 80% and preferably at
least about 90%, and more preferably about 100% of the lenses worn
in the patient population display depositions rated as none or
slight, over the wear period.
[0025] Suitable amounts of high molecular weight hydrophilic
polymer include from about 1 to about 15 weight percent, more
preferably about 3 to about 15 percent, most preferably about 5 to
about 12 percent, all based upon the total weight of all reactive
components.
[0026] Examples of high molecular weight hydrophilic polymers
include but are not limited to polyamides, polylactones,
polyimides, polylactams and functionalized polyamides,
polylactones, polyimides, polylactams, such as DMA functionalized
by copolymerizing DMA with a lesser molar amount of a
hydroxyl-functional monomer such as HEMA, and then reacting the
hydroxyl groups of the resulting copolymer with materials
containing radical polymerizable groups, such as
isocyanatoethylmethacrylate or methacryloyl chloride. Hydrophilic
prepolymers made from DMA or N-vinyl pyrrolidone with glycidyl
methacrylate may also be used. The glycidyl methacrylate ring can
be opened to give a diol which may be used in conjunction with
other hydrophilic prepolymer in a mixed system to increase the
compatibility of the high molecular weight hydrophilic polymer,
hydroxyl-functionalized silicone containing monomer and any other
groups which impart compatibility. The preferred high molecular
weight hydrophilic polymers are those that contain a cyclic moiety
in their backbone, more preferably, a cyclic amide or cyclic imide.
High molecular weight hydrophilic polymers include but are not
limited to poly-N-vinyl pyrrolidone, poly-N-vinyl-2- piperidone,
poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2- caprolactam,
poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl-2-
piperidone, poly-N-vinyl-4-methyl-2-caprolactam,
poly-N-vinyl-3-ethyl-2- pyrrolidone, and
poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole,
poly-N-N-dimethylacrylamide, polyvinyl alcohol, polyacrylic acid,
polyethylene oxide, poly 2 ethyl oxazoline, heparin
polysaccharides, polysaccharides, mixtures and copolymers
(including block or random, branched, multichain, comb-shaped or
star shaped) thereof where poly-N-vinylpyrrolidone (PVP) is
particularly preferred. Copolymers might also be used such as graft
copolymers of PVP.
[0027] The high molecular weight hydrophilic polymers provide
improved wettability, and particularly improved in vivo wettability
to the medical devices of the present invention. Without being
bound by any theory, it is believed that the high molecular weight
hydrophilic polymers are hydrogen bond receivers which in aqueous
environments, hydrogen bond to water, thus becoming effectively
more hydrophilic. The absence of water facilitates the
incorporation of the hydrophilic polymer in the reaction mixture.
Aside from the specifically named high molecular weight hydrophilic
polymers, it is expected that any high molecular weight polymer
will be useful in this invention provided that when said polymer is
added to a silicone hydrogel formulation, the hydrophilic polymer
(a) does not substantially phase separate from the reaction mixture
and (b) imparts wettability to the resulting cured polymer. In some
embodiments it is preferred that the high molecular weight
hydrophilic polymer be soluble in the diluent at processing
temperatures.
[0028] Manufacturing processes which use water or water soluble
diluents may be preferred due to their simplicity and reduced cost.
In these embodiments high molecular weight hydrophilic polymers
which are water soluble at processing temperatures are
preferred.
[0029] Compatibilizinq Component
[0030] As used herein a "compatibilizing component" is a compound
having a number average molecular weight of about less than 5000
Daltons, and preferably less than about 3000 Daltons, and
containing at least one polymerizable group, which is capable of
solubilizing the selected reactive components. Without a
compatibilizing component the high molecular weight hydrophilic
polymer and oxygen permeable components are insufficiently
miscible, and cannot, with reasonable processing conditions, form
an optically transparent ophthalmic device. The compatibilizing
component of the present invention solubilizes the oxygen permeable
component(s) and high molecular weight hydrophilic polymer via
hydrogen bonding, dispersive forces, combinations thereof and the
like. Thus any functionality which reacts in any of these ways with
the hydrophilic polymer may be used as a compatibilizing component.
Macromers (number average molecular weights of between about 5000
and about 15,000 Daltons) may also be used so long as they have the
compatibilizing functionality described herein. If a
compatibilizing macromer is used it may still be necessary to add
an additional compatibilizing component to get the desired level of
wettability in the resulting ophthalmic device.
[0031] One suitable class of compatibilizing components of the
present invention comprise at least one active hydrogen and at
least one siloxane group. An active hydrogen has the ability to
hydrogen bond with the hydrophilic polymer and any hydrophilic
monomers present. Hydroxyl groups readily participate in hydrogen
bonding and are therefore a preferred source of active hydrogens.
Thus, in one embodiment, the compatibilizing components of the
present invention beneficially comprise at least one hydroxyl group
and at least one "--Si--O--Si--"group. It is preferred that
silicone and its attached oxygen account for more than about 10
weight percent of said compatibilizing component, more preferably
more than about 20 weight percent.
[0032] The ratio of Si to OH in the compatibilizing component is
also important to providing a compatibilzing component which will
provide the desired degree of compatibilization. If the ratio of
hydrophobic portion to OH is too high, the compatibilizing
component may be poor at compatibilizing the hydrophilic polymer,
resulting in incompatible reaction mixtures. Accordingly, in some
embodiments, the Si to OH ratio is less than about 15:1, and
preferably between about 1:1 to about 10:1. In some embodiments
primary alcohols have provided improved compatibility compared to
secondary alcohols. Those of skill in the art will appreciate that
the amount and selection of compatibilizing component will depend
on how much hydrophilic polymer is needed to achieve the desired
wettability and the degree to which the silicone containing monomer
is incompatible with the hydrophilic polymer. Examples of
compatibilizing components include monomers of Formulae I and
II
##STR00001##
wherein: [0033] n is an integer between 3 and 35, and preferably
between 4 and 25; [0034] R.sup.1 is hydrogen, C.sub.1-6alkyl,;
[0035] R.sup.2,R.sup.3, and R.sup.4, are independently,
C.sub.1-6alkyl, triC.sub.1-6alkylsiloxy, phenyl, naphthyl,
substituted C.sub.i-6alkyl, substituted phenyl, or substituted
naphthyl where the alkyl substitutents are selected from one or
more members of the group consisting of C.sub.1-6alkoxycarbonyl,
C.sub.1-6alkyl, C.sub.1-6alkoxy, amide, halogen, hydroxyl,
carboxyl, C.sub.1-6alkylcarbonyl and formyl, and where the aromatic
substitutents are selected from one or more members of the group
consisting of C.sub.1-6alkoxycarbonyl, C.sub.1-6alkyl,
C.sub.1-6alkoxy, amide, halogen, hydroxyl, carboxyl,
C.sub.1-6alkylcarbonyl and formyl; [0036] R.sup.5 is hydroxyl, an
alkyl group containing one or more hydroxyl groups, or
(CH.sub.2(CR.sup.9R.sup.10).sub.yO).sub.x)--R.sup.11 wherein y is 1
to 5, preferably 1 to 3, x is an is an integer of 1 to 100,
preferably 2 to 90 and more preferably 10 to 25; R.sup.9-R.sup.11
are independently selected from H, alkyl having up to 10 carbon
atoms and alkyls having up to 10 carbon atoms substituted with at
least one polar functional group; [0037] R.sup.6 is a divalent
group comprising up to 20 carbon atoms; [0038] R.sup.7 is a
monovalent group that can undergo free radical and/or cationic
polymerization comprising up to 20 carbon atoms; and [0039] R.sup.8
is a divalent or trivalent group comprising up to 20 carbon
atoms.
[0040] Reaction mixtures of the present invention may include more
than one compatibilizing component.
[0041] For monofunctional compatibilizing components the preferred
R.sup.1 is hydrogen, and the preferred R.sup.2,R.sup.3, and
R.sup.4, are C.sub.1-6alkyl and triC.sub.1-6alkylsiloxy, most
preferred methyl and trimethylsiloxy. For multifunctional
(difunctional or higher) R.sup.1-R.sup.4 independently comprise
ethylenically unsaturated polymerizable groups and more preferably
comprise an acrylate, a styryl, a C.sub.1-6alkylacrylate,
acrylamide, C.sub.1-6alkylacrylamide, N-vinyllactam, N-vinylamide,
C.sub.2-12alkenyl, C.sub.2-12alkenylphenyl,
C.sub.2-12alkenylnaphthyl, or
C.sub.2-6alkenylphenylC.sub.1-6alkyl.
[0042] The preferred R.sup.5 is hydroxyl, --CH.sub.2OH or
CH.sub.2CHOHCH.sub.2OH, with hydroxyl being most preferred.
[0043] The preferred R.sup.6 is a divalent C.sub.1-6alkyl,
C.sub.1-6alkyloxy, C.sub.1-6alkyloxyC.sub.1-6alkyl, phenylene,
naphthalene, C.sub.1-12cycloalkyl, C.sub.1-6alkoxycarbonyl, amide,
carboxy, C.sub.1-6alkylcarbonyl, carbonyl, C.sub.1-6alkoxy,
substituted C.sub.1-6alkyl, substituted C.sub.1-6alkyloxy,
substituted C.sub.1-6alkyloxyC.sub.1-6alkyl, substituted phenylene,
substituted naphthalene, substituted C.sub.1-12cycloalkyl, where
the substituents are selected from one or more members of the group
consisting of C.sub.1-6alkoxycarbonyl, C.sub.1-6alkyl,
C.sub.1-6alkoxy, amide, halogen, hydroxyl, carboxyl,
C.sub.1-6alkylcarbonyl and formyl. The particularly preferred
R.sup.6 is a divalent methyl(methylene).
[0044] The preferred R.sup.7 comprises a free radical reactive
group, such as an acrylate, a styryl, vinyl, vinyl ether, itaconate
group, a C.sub.1-6alkylacrylate, acrylamide,
C.sub.1-6alkylacrylamide, N-vinyllactam, N-vinylamide,
C.sub.2-12alkenyl, C.sub.2-12alkenylphenyl,
C.sub.2-12alkenylnaphthyl, or C.sub.2-6alkenylphenylC.sub.1-6alkyl
or a cationic reactive group such as vinyl ether or epoxide groups.
The particulary preferred R.sup.7 is methacrylate.
[0045] The preferred R.sup.8 is is a divalent C.sub.1-6alkyl,
C.sub.1-6alkyloxy, C.sub.1-6alkyloxyC.sub.1-6alkyl, phenylene,
naphthalene, C.sub.1-6cycloalkyl, C.sub.1-6alkoxycarbonyl, amide,
carboxy, C.sub.1-6alkylcarbonyl, carbonyl, C.sub.1-6alkoxy,
substituted C.sub.1-6alkyl, substituted C.sub.1-6alkyloxy,
substituted C.sub.1-6alkyloxyC.sub.1-6alkyl, substituted phenylene,
substituted naphthalene, substituted C.sub.1-ucycloalkyl, where the
substituents are selected from one or more members of the group
consisting of C.sub.1-6alkoxycarbonyl, C.sub.1-6alkyl,
C.sub.1-6alkoxy, amide, halogen, hydroxyl, carboxyl,
C.sub.1-6alkylcarbonyl and formyl. The particularly preferred
R.sup.8 is C.sub.1-6alkyloxyC.sub.1-6alkyl.
[0046] Examples of compatibilizing component of Formula I that are
particularly preferred are 2-propenoic acid,
2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[trimethylsilyl)oxy]disilo-
xanyl]propoxy]propyl ester (which can also be named
(3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane-
.
##STR00002##
[0047] The above compound,
(3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane
is formed from an epoxide, which produces an 80:20 mixture of the
compound shown above and
(2-methacryloxy-3-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane-
. In the present invention the 80:20 mixture is preferred over pure
(3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane-
. In some embodiments of the present invention it is preferred to
have some amount of the primary hydroxyl present, preferably
greater than about 10 wt % and more preferably at least about 20 wt
%
[0048] Other suitable hydroxyl-functionalized silicone containing
monomers include
(3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)sil-
ane
##STR00003##
bis-3-methacryloxy-2-hydroxypropyloxypropyl
polydimethylsiloxane
##STR00004##
3-methacryloxy-2-(2-hydroxyethoxy)propyloxy)propylbis(trimethylsiloxy)met-
hylsilane
##STR00005##
N-2-methacryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl)silyl
carbamate
##STR00006##
N,N,N',N'-tetrakis(3-methacryloxy-2-hydroxypropyl)-a,w-bis-3-aminopropyl--
polydimethylsiloxane
##STR00007##
[0049] The reaction products of glycidyl methacrylate with
amino-functional polydimethylsiloxanes may also be used as a
compatibilizing components.
[0050] Other suitable compatibilizing components include those
disclosed in columns 6,7 and 8 of U.S. Pat. No. 5,994,488, and
monomers disclosed in U.S. Pat. Nos. 4,259,467; 4,260,725;
4,261,875; 4,649,184; 4,139,513, 4,139,692; US 2002/0016383; U.S.
Pat. Nos. 4,139,513 and 4,139,692. These and any other patents or
applications cited herein are incorporated by reference.
[0051] Still additional structures which may be suitable
compatibilizing components include those similar to the compounds
disclosed in Pro. ACS Div. Polym. Mat. Sci. Eng., April 13-17,
1997, p. 42, and having the following structure:
##STR00008##
where n=1-50 and R independently comprise H or a polymerizable
unsaturated group), with at least one R comprising a polymerizable
group, and at least one R, and preferably 3-8 R, comprising H.
[0052] A second suitable class of compatibilizing components
include those having the structure given in Formula III, below:
IWA-HB-[IWA-HB].sub.x-IWA
[0053] Wherein x is 1 to 10;
[0054] IWA is a difunctional hydrophilic polymer as defined below,
but having a number average molecular weight of between about 1000
and about 50,000 Daltons; and
[0055] HB is a difunctional moeity comprising at least one N which
is capable of hydrogen bonding with active hydrogens in the
hydrophilic polymer and any other component having active
hydrogens.
[0056] Preferred IWA groups may be derived from {acute over
(.alpha.)},.omega.-hydroxyl terminated PVP and {acute over
(.alpha.)},.omega.-hydroxyl terminated polyoxyalkylene glycols
having number average molecular weights between about 1,000 and
about 50,000 Daltons.
[0057] Preferred HB groups include difunctional amides, imides,
carbamates and ureas, combinations thereof and the like.
[0058] Compatibilizing components of Formula III may be made by
amine terminated polyoxyalkyleneglycols (Jeffamines) reacted with
isocyanates, chloroformates or acyl chlorides or anhydrides.
[0059] Additional suitable compatibilizing components are disclosed
in U.S. Pat. No. 4,235,985 which is hereby incorporated by
reference.
[0060] Suitable compatibilizing components may also comprise
silicone containing macromers which have been modified to include
compatibilizing functionality as defined above. Such macromers
comprise substantial quantities of both Si and HB groups as
defined, above, or active hydrogen functionality, such as hydroxyl
groups. One class of suitable macromers include hydroxyl
functionalized macromers made by Group Transfer Polymerization
(GTP), or styrene functionalized prepolymers of hydroxyl functional
methacrylates and silicone methacrylates and are disclosed in U.S.
Pat. No. 6,367,929, which is incorporated herein by reference. In
the present invention, these macromers are preferably used with
another compatibilizing component, such as a siloxane containing
monomer. Other macromers, such as those made by radical
polymerization or condensation reaction may also be used
independently or in combination with other compatibilizing
components so long as the Si to hydrogen molar ratio (OH) of the
macromer is less than about 15:1, and preferably between about 1:1
to about 10:1 or the Si to HB molar ratio is less than about 10:1
and preferably between about 1:1 and about 8:1. However, those of
skill in the art will appreciate that including difluoromethylene
groups will decrease the molar ratio suitable for providing
compatibility.
[0061] Suitable monofunctional compatibilizing components are
commercially available from Gelest, Inc. Morrisville, Pa. Suitable
multifunctional compatibilizing components are commercially
available from Gelest, Inc, Morrisville, Pa. or may be made using
the procedures disclosed in U.S. Pat. Nos. 5,994,488 and 5,962,548.
Suitable PEG type monofunctional compatibilizing components may be
made using the procedures disclosed in PCT/J P02/02231.
[0062] Suitable compatibilizing macromers may be made using the
general procedure disclosed in U.S. Pat. No. 5,760,100 (material C)
or U.S. Pat. No. 6,367,929.
[0063] While compatibilizing components comprising hydroxyl
functionality have been found to be particularly suitable for
providing compatible polymers for biomedical devices, and
particulalrly ophthalmic devices, any compatibilizing component
which, when polymerized and/or formed into a final article is
compatible with the selected hydrophilic components may be used.
Compatibilizing components may be selected using the following
monomer compatibility test. In this test one gram of each of
mono-3-methacryloxypropyl terminated, mono-butyl terminated
polydimethylsiloxane (mPDMS MW 800-1000) and a monomer to be tested
are mixed together in one gram of 3,7-dimethyl-3-octanol at about
20.degree. C. A mixture of 12 weight parts K-90 PVP and 60 weight
parts DMA is added drop-wise to hydrophobic component solution,
with stirring, until the solution remains cloudy after three
minutes of stirring. The mass of the added blend of PVP and DMA is
determined in grams and recorded as the monomer compatibility
index. Any compatibilizing component having a compatibility index
of greater than 0.5 grams, more preferably greater than about 1
grams and most preferably greater than about 1.5 grams will be
suitable for use in this invention. Those of skill in the art will
appreciate that the molecular weight of the active compatibilizing
component will effect the results of the above test.
Compatibilizing components having molecular weights greater than
about 800 daltons may need to mix for longer periods of time to
give representative results.
[0064] An "effective amount" of the compatibilizing component of
the invention is the amount needed to compatibilize or dissolve the
high molecular weight hydrophilic polymer and the other components
of the polymer formulation. Thus, the amount of compatibilizing
component will depend in part on the amount of hydrophilic polymer
which is used, with more compatibilizing component being needed to
compatibilize higher concentrations of high molecular weight
hydrophilic polymer. Effective amounts of compatibilizing component
in the polymer formulation include about 5% (weight percent, based
on the total weight of the reactive components) to about 90%,
preferably about 10% to about 80%, most preferably, about 20% to
about 50%.
[0065] In addition to the high molecular weight hydrophilic
polymers and the compatibilizing components of the invention other
hydrophilic monomers, oxygen permeability enhancing components,
crosslinkers, additives, diluents, polymerization initators may be
used to prepare the biomedical devices of the invention.
Oxygen Permeable Component
[0066] The compositions and devices of the present invention may
further comprise additional components which provide enhanced
oxygen permeability compared to a conventional hydrogel. Suitable
oxygen permeable components include siloxane containing monomers,
macromers and reactive prepolymers, fluorine containing monomers,
macromers and reactive prepolymers and carbon-carbon triple bond
containing monomers, macromers and reactive prepolmers and
combinations thereof, but exclude the compatibilizing component.
For the purposes of this invention, the term macromer will be used
to cover both macromers and prepolymers. Preferred oxygen permeable
components comprise siloxane containing monomers, macromers, and
mixtures thereof
[0067] Suitable siloxane containing monomers include, amide analogs
of TRIS described in U.S. Pat. No. 4,711,943, vinylcarbamate or
carbonate analogs decribed in U.S. Pat. No. 5,070,215, and monomers
contained in U.S. Pat. No. 6,020,445 are useful and these
aforementioned patents as well as any other patents mentioned in
this specification are hereby incorporated by reference. More
specifically, 3-methacryloxypropyltris(trimethylsiloxy)silane
(TRIS), monomethacryloxypropyl terminated polydimethylsiloxanes,
polydimethylsiloxanes,
3-methacryloxypropylbis(trimethylsiloxy)methylsilane,
methacryloxypropylpentamethyl disiloxane and combinations thereof
are particularly useful as siloxane containing monomers of the
invention. Additional siloxane containing monomers may be present
in amounts of about 0 to about 75 wt %, more preferably of about 5
and about 60 and most preferably of about 10 and 40 weight %.
[0068] Suitable siloxane containing macromers have a number average
molecular weight between about 5,000 and about 15,000 Daltons.
Siloxane containing macromers include materials comprising at least
one siloxane group, and preferably at least one dialkyl siloxane
group and more preferably at least one dimethyl siloxane group. The
siloxane containing macromers may include other components such as
urethane groups, alkylene or alkylene oxide groups, polyoxyalkalene
groups, arylene groups, alkyl esters, amide groups, carbamate
groups, perfluoroalkoxy groups, isocyanate groups, combinations
thereof of and the like. A preferred class of siloxane containing
macromers may be formed via the polymerization of one or more
siloxanes with one or more acrylic or methacrylic materials.
Siloxane containing macromers may be formed via group transfer
polymerization ("GTP"), free radical polymerization, condensation
reactions and the like. The siloxane containing macromers may be
formed in one or a series of steps depending on the components
selected and using conditions known in the art. Specific siloxane
containing macromers, and methods for their manufucture, include
those disclosed in U.S. Pat. No. 5,760,100 as materials A-D
(methacrylate functionalized, silicone-fluoroether urethanes and
methacrylate functionalized, silicone urethanes), and those
disclosed in U.S. Pat. No. 6,367,929 (styrene functionalized
prepolymers of hydroxyl functional methacrylates and silicone
methacrylates), the disclosures of which are incorporated herein by
reference.
[0069] Suitable siloxane containing reactive prepolymers include
vinyl carbamate functionalized polydimethylsiloxane, which is
further disclosed in U.S. Pat. No. 5,070215 and urethane based
prepolymers comprising alternating "hard" segments formed from the
reaction of short chained diols and diisocyantes and "soft"
segments formed from a relatively high molecular weight polymer,
which is a,w endcapped with two active hydrogens. Specific examples
of suitable siloxane containing prepolymers, and methods for their
manufacture, are disclosed in U.S. Pat. No. 5,034,461, which is
incorporated herein by reference.
[0070] The hydrogels of the present invention may comprise at least
one siloxane containing macromer. The siloxane containing macromer
may be present in amounts between about 5 and about 50 weight %,
preferably between about 10 and about 50 weight % and more
preferably between about 15 and about 45 weight %, all based upon
the total weight of the reactive components.
[0071] Suitable fluorine containing monomers include
fluorine-containing (meth)acrylates, and more specifically include,
for example, fluorine-containing C.sub.2-C.sub.12alkyl esters of
(meth)acrylic acid such as 2,2,2-trifluoroethyl(meth)acrylate,
2,2,2,2',2',2'-hexafluoroisopropyl(meth)acrylate, 2,2,3,
3,4,4,4-heptafluorobutyl(meth)acrylate,
2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctyl(meth)acrylate,
2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-hexadecafluorononyl(meth)acrylate
and the like. Fluorine containing macromers and reactive
prepolymers include macromers and prepolymers which include said
flurorine containing monomers.
[0072] It has been found that wettability of macromer containing
silicone hydrogels may be improved by including at least one
hydrophilic polymer and a compatibilizing component. Improved
wettability includes a decrease in advancing dynamic contact angle
of at least about 10%, and preferably at least about 20% and in
some embodiment a decrease of at least about 50%. In certain
embodiments it may be preferred to use mixtures of siloxane
containing monomers or mixtures of siloxane containing monomers
with siloxane containing macromers or prepolymers.
Hydrophilic Monomers
[0073] Additionally, reactive components of the present invention
may also include any hydrophilic monomers used to prepare
conventional hydrogels. For example monomers containing acrylic
groups (CH.sub.2.dbd.CROX, where R is hydrogen or C.sub.1-6alkyl an
X is O or N) or vinyl groups (--C.dbd.CH.sub.2) may be used.
Examples of additional hydrophilic monomers are
N,N-dimethylacrylamide, 2-hydroxyethyl methacrylate, glycerol
monomethacrylate, 2-hydroxyethyl methacrylamide, polyethyleneglycol
monomethacrylate, methacrylic acid, acrylic acid, N-vinyl
pyrrolidone, N-vinyl-N-methyl acetamide, N-vinyl-N-ethyl acetamide,
N-vinyl-N-ethyl formamide, N-vinyl formamide and and combinations
thereof.
[0074] Aside the additional hydrophilic monomers mentioned above,
polyoxyethylene polyols having one or more of the terminal hydroxyl
groups replaced with a functional group containing a polymerizable
double bond may be used. Examples include polyethylene glycol, as
disclosed in U.S. Pat. No. 5,484,863, ethoxylated alkyl glucoside,
as disclosed in U.S. Pat. No. 5,690,953, U.S. Pat. No. 5,304,584,
and ethoxylated bisphenol A, as disclosed in U.S. Pat. No.
5,565,539, reacted with one or more molar equivalents of an
end-capping group such as isocyanatoethyl methacrylate, methacrylic
anhydride, methacryloyl chloride, vinylbenzoyl chloride, and the
like, produce a polyethylene polyol having one or more terminal
polymerizable olefinic groups bonded to the polyethylene polyol
through linking moieties such as carbamate, urea or ester
groups.
[0075] Still further examples include the hydrophilic vinyl
carbonate or vinyl carbamate monomers disclosed in U.S. Pat. No.
5,070,215, the hydrophilic oxazolone monomers disclosed in U.S.
Pat. No. 4,910,277, and polydextran.
[0076] The preferred additional hydrophilic monomers are
N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA),
glycerol methacrylate, 2-hydroxyethyl methacrylamide,
N-vinylpyrrolidone (NVP), polyethyleneglycol monomethacrylate,
methacrylic acid, acrylic acid and combinations thereof, with
hydrophilic monomers comprising DMA being particularly preferred.
Additional hydrophilic monomers may be present in amounts of about
0 to about 70 wt %, more preferably of about 5 and about 60 and
most preferably of about 10 and 50 weight %, based upon the total
weight of the reactive components.
Crosslinkers
[0077] Suitable crosslinkers are compounds with two or more
polymerizable functional groups. The crosslinker may be hydrophilic
or hydrophobic and in some embodiments of the present invention
mixtures of hydrophilic and hydrophobic crosslinkers have been
found to provide silicone hydrogels with improved optical clarity
(reduced haziness compared to a CSI Thin Lens.RTM.). Examples of
suitable hydrophilic crosslinkers include compounds having two or
more polymerizable functional groups, as well as hydrophilic
functional groups such as polyether, amide or hydroxyl groups.
Specific examples include TEGDMA (tetraethyleneglycol
dimethacrylate), TrEGDMA (triethyleneglycol dimethacrylate),
ethyleneglycol dimethacylate (EGDMA), ethylenediamine
dimethyacrylamide, glycerol dimethacrylate and combinations thereof
Examples of suitable hydrophobic crosslinkers include
multifunctional compatibilizing component, multifunctional
polyether-polydimethylsiloxane block copolymers, combinations
thereof and the like. Specific hydrophobic crosslinkers include
acryloxypropyl terminated polydimethylsiloxane (n=10 or 20)
(acPDMS), hydroxylacrylate functionalized siloxane macromer,
methacryloxypropyl terminated PDMS, butanediol dimethacrylate,
divinyl benzene,
1,3-bis(3-methacryloxypropyl)tetrakis(trimethylsiloxy)disiloxane
and mixtures thereof. Preferred crosslinkers include TEGDMA, EGDMA,
acPDMS and combinations thereof. The amount of hydrophilic
crosslinker used is generally about 0 to about 2 weight % and
preferably from about 0.5 to about 2 weight % and the amount of
hydrophobic crosslinker is about 0 to about 0 to about 5 weight %
based upon the total weight of the reactive components, which can
alternatively be referred to in mol% of about 0.01 to about 0.2
mmole/gm reactive components, preferably about 0.02 to about 0.1
and more preferably 0.03 to about 0.6 mmole/gm.
[0078] Increasing the level of crosslinker in the final polymer has
been found to reduce the amount of haze. However, as crosslinker
concentration increases above about 0.15 mmole/gm reactive
components modulus increases above generally desired levels
(greater than about 90 psi). Thus, in the present invention the
crosslinker composition and amount is selected to provide a
crosslinker concentration in the reaction mixture of between about
1 and about 10 mmoles crosslinker per 100 grams of reactive
components.
[0079] Additional components or additives, which are generally
known in the art may also be included. Additives include but are
not limited to ultra-violet absorbing compounds and monomer,
reactive tints, antimicrobial compounds, pigments, photochromic,
release agents, combinations thereof and the like.
[0080] Diluents
[0081] The reactive components (compatibilizing component,
hydrophilic polymer, oxygen permeable components, hydrophilic
monomers, crosslinker(s) and other components) are mixed and
reacted in the absence of water and optionally, in the presence of
at least one diluent to form a reaction mixture. The type and
amount of diluent used also effects the properties of the resultant
polymer and article. The haze and wettability of the final article
may be improved by selecting relatively hydrophobic diluents and/or
decreasing the concentration of diluent used. As discussed above,
increasing the hydrophobicity of the diluent may also allow poorly
compatible components (as measured by the compatibility test) to be
processed to form a compatible polymer and article. However, as the
diluent becomes more hydrophobic, processing steps necessary to
replace the diluent with water will require the use of solvents
other than water. This may undesirably increase the complexity and
cost of the manufacturing process. Thus, it is important to select
a diluent which provides the desired compatibility to the
components with the necessary level of processing convenience.
Diluents useful in preparing the devices of this invention include
ethers, esters, alkanes, alkyl halides, silanes, amides, alcohols
and combinations thereof. Amides and alcohols are preferred
diluents, and secondary and tertiary alcohols are most preferred
alcohol diluents. Examples of ethers useful as diluents for this
invention include tetrahydrofuran, tripropylene glycol methyl
ether, dipropylene glycol methyl ether, ethylene glycol n-butyl
ether, diethylene glycol n-butyl ether, diethylene glycol methyl
ether, ethylene glycol phenyl ether, propylene glycol methyl ether,
propylene glycol methyl ether acetate, dipropylene glycol methyl
ether acetate, propylene glycol n-propyl ether, dipropylene glycol
n-propyl ether, tripropylene glycol n-butyl ether, propylene glycol
n-butyl ether, dipropylene glycol n-butyl ether, tripropylene
glycol n-butyl ether, propylene glycol phenyl ether dipropylene
glycol dimetyl ether, polyethylene glycols, polypropylene glycols
and mixtures thereof. Examples of esters useful for this invention
include ethyl acetate, butyl acetate, amyl acetate, methyl lactate,
ethyl lactate, i-propyl lactate. Examples of alkyl halides useful
as diluents for this invention include methylene chloride. Examples
of silanes useful as diluents for this invention include
octamethylcyclotetrasiloxane.
[0082] Examples of alcohols useful as diluents for this invention
include those having the formula
##STR00009##
wherein Where R, R' and R'' are independently selected from H, a
linear, branched or cyclic monovalent alkyl having 1 to 10 carbons
which may optionally be substituted with one or more groups
including halogens, ethers, esters, aryls, aminos, amides, alkenes,
alkynes, carboxylic acids, alcohols, aldehydes, ketones or the
like, or any two or all three of R, R and R'' can together bond to
form one or more cyclic structures, such as alkyl having 1 to10
carbons which may also be substituted as just described, with the
proviso that no more than one of R, R' or R'' is H.
[0083] It is preferred that R, R' and R'' are independently
selected from H or unsubstituted linear, branched or cyclic alkyl
groups having 1 to 7 carbons. It is more preferred that R, R', and
R'' are independently selected form unsubstituted linear, branched
or cyclic alkyl groups having 1 to 7 carbons. In certain
embodiments, the preferred diluent has 4 or more, more preferably 5
or more total carbons, because the higher molecular weight diluents
have lower volatility, and lower flammability. When one of the R,
R' and R'' is H, the structure forms a secondary alcohol. When none
of the R, R' and R'' are H, the structure forms a tertiary alcohol.
Tertiary alcohols are more preferred than secondary alcohols. The
diluents are preferably inert and easily displaceable by water when
the total number of carbons is five or less.
[0084] Examples of useful secondary alcohols include 2-butanol,
2-propanol, menthol, cyclohexanol, cyclopentanol and exonorborneol,
2-pentanol, 3-pentonal, 2-hexanol, 3-hexanol, 3-methyl-2-butanol,
2-heptanol, 2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol,
and the like.
[0085] Examples of useful tertiary alcohols include tert-butanol,
tert-amyl, alcohol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol,
3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol,
3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol,
2-methyl-2-heptanol, 2-methyl-2-octanol, 2-2methyl-2-nonanol,
2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl-3-heptanol,
4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4-octanol,
3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol,
3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol,
4-propyl-4-heptanol, 4-isopropyl-4-heptanol,
2,4-dimethyl-2-pentanol, 1-methylcyclopentanol,
1-ethylcyclopentanol, 1-ethylcyclopentanol,
3-hydroxy-3-methyl-1-butene, 4-hydroxy-4-methyl-1-cyclopentanol,
2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol
2,3,4-trimethyl-3-pentanol, 3,7-dimethyl-3-octanol,
2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanol and
3-ethyl-3-pentanol, and the like.
[0086] A single alcohol or mixtures of two or more of the
above-listed alcohols or two or more alcohols according to the
structure above can be used as the diluent to make the polymer of
this invention.
[0087] In certain embodiments, the preferred alcohol diluents are
secondary and tertiary alcohols having at least 4 carbons. The more
preferred alcohol diluents include tert-butanol, tert-amyl alcohol,
2-butanol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol,
3-methyl-3-pentanol, 3-ethyl-3-pentanol,
3,7-dimethyl-3-octanol.
[0088] Presently, the most preferred diluents are hexanol,
heptanol, octanol, nonanol, decanol, tert-butyl alcohol,
3-methyl-3-pentanol, isopropanol, t amyl alcohol, ethyl lactate,
methyl lactate, i-propyl lactate, 3,7-dimethyl-3-octanol, dimethyl
formamide, dimethyl acetamide, dimethyl propionamide, N methyl
pyrrolidinone and mixtures thereof. Additional diluents useful for
this invention are disclosed in U.S. Pat. No. 6,020,445, which is
incorporated herein by reference.
[0089] In one embodiment of the present invention the diluent is
water soluble at processing conditions and readily washed out of
the lens with water in a short period of time. Suitable water
soluble diluents include 1-ethoxy-2-propanol, 1-methyl-2-propanol,
t-amyl alcohol, tripropylene glycol methyl ether, isopropanol,
1-methyl-2-pyrrolidone, N,N-dimethylpropionamide, ethyl lactate,
dipropylene glycol methyl ether, mixtures thereof and the like. The
use of a water soluble diluent allows the post molding process to
be conducted using water only or aqueous solutions which comprise
water as a substantial component.
[0090] In one embodiment, the amount of diluent is generally less
than about 50 weight % of the reaction mixture and preferably less
than about 40 weight % and more preferably between about 10 and
about 30 weight % based upon the total weight of the components of
the reaction mixture.
[0091] The diluent may also comprise additional components such as
release agents. Suitable release agents are water soluble and aid
in lens deblocking
[0092] The polymerization initiators includes compounds such as
lauryl peroxide, benzoyl peroxide, isopropyl percarbonate,
azobisisobutyronitrile, and the like, that generate free radicals
at moderately elevated temperatures, and photoinitiator systems
such as aromatic alpha-hydroxy ketones, alkoxyoxybenzoins,
acetophenones, acyl phosphine oxides, and a tertiary amine plus a
diketone, mixtures thereof and the like. Illustrative examples of
photoinitiators are 1-hydroxycyclohexyl phenyl ketone,
2-hydroxy-2-methyl-1-phenyl-propan-1-one,
bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide
(DMBAPO), bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide
(Irgacure 819), 2,4,6-trimethylbenzyldiphenyl phosphine oxide,
2,4,6-trimethylbenzyoyl diphenylphosphine oxide, benzoin methyl
ester,and a combination of camphorquinone and ethyl
4-(N,N-dimethylamino)benzoate. Commercially available visible light
initiator systems include Irgacure 819, Irgacure 1700, Irgacure
1800, Irgacure 1850 (all from Ciba Specialty Chemicals) and Lucirin
TPO initiator (available from BASF). Commercially available UV
photoinitiators include Darocur 1173 and Darocur 2959 (Ciba
Specialty Chemicals). The initiator is used in the reaction mixture
in effective amounts to initiate photopolymerization of the
reaction mixture, e.g., from about 0.1 to about 2 parts by weight
per 100 parts of reactive monomer. Polymerization of the reaction
mixture can be initiated using the appropriate choice of heat or
visible or ultraviolet light or other means depending on the
polymerization initiator used. Alternatively, initiation can be
conducted without a photoinitiator using, for example, e-beam.
However, when a photoinitiator is used, the preferred initiator is
a combination of 1-hydroxycyclohexyl phenyl ketone and
bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide
(DMBAPO), and the preferred method of polymerization initiation is
visible light. The most preferred is
bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide (Irgacure
819).
[0093] The preferred range of all silicone containing components
(oxygen permeable components and compatibilizing components) is
from about 5 to 99 weight percent, more preferably about 15 to 90
weight percent, and most preferably about 25 to about 80 weight
percent, based upon the total weight of the reactive components. A
preferred range of compatibilizing components is about 5 to about
90 weight percent, preferably about 10 to about 80, and most
preferably about 20 to about 50 weight percent. A preferred range
of hydrophilic monomer is from about 5 to about 80 weight percent,
more preferably about 5 to about 60 weight percent, and most
preferably about 10 to about 50 weight percent of the reactive
components in the reaction mixture. A preferred range of high
molecular weight hydrophilic polymer is about 1 to about 15 weight
percent, more preferably about 3 to about 15 weight percent, and
most preferably about 5 to about 12 weight percent. A preferred
range of macromer is from about 5 to about 50 weight %, preferably
from about 10 to about 50 weight % and more preferably from about
15 to about 45 weight %. All of the foregoing ranges are based upon
the total weight of all reactive components.
[0094] A preferred range of diluent is from about 0 to about 70
weight percent, more preferably about 0 to about 50 weight percent,
and still more preferably about 0 to about 40 weight percent and in
some embodiments, most preferably between about 10 and about 30
weight percent based upon the weight of all components in the total
reaction mixture. The amount of diluent required varies depending
on the nature and relative amounts of the reactive components.
[0095] The invention further comprises, consists and consists
essentially of a silicone hydrogel, biomedical device, ophthalmic
device and contact lenses of the formulations shown below:
TABLE-US-00001 Wt % components CC HMWHP ASCM SCM HM 5-90 1-15, 3-15
or 5-12 0 0 0 10-80 1-15, 3-15 or 5-12 0 0 0 15-55 1-15, 3-15 or
5-12 0 0 0 5-90 1-15, 3-15 or 5-12 5-50 10-80 1-15, 3-15 or 5-12
10-50 15-55 1-15, 3-15 or 5-12 15-45 5-90 1-15, 3-15 or 5-12 0-80,
5-60 5-50; 10-50; 0-70, 5-60 or or 10-40 15-45 10-50 10-80 1-15,
3-15 or 5-12 0-80, 5-60 5-50; 10-50; 0-70, 5-60 or or 10-40 15-45
10-50 15-55 1-15, 3-15 or 5-12 0-80, 5-60 5-50; 10-50; 0-70, 5-60
or or 10-40 15-45 10-50 CC is compatibilizing component HMWHP is
high molecular weight hydrophilic polymer ASCM is additional
siloxane containing monomer HM is hydrophilic monomer SCM is a
siloxane containing macromer
[0096] Thus, the present invention includes silicone hydrogel,
biomedical device, ophthalmic device and contact lenses having each
of the composition listed in the table, which describes 261
possible compositional ranges. Each of the ranges listed above is
prefaced by the word "about". The foregoing range combinations are
presented with the proviso that the listed components, and any
additional components add up to 100 weight %.
[0097] In a preferred embodiment, the reactive components comprise
about 28 wt. % SiGMA; about 31 wt. % 800-1000 MW
monomethacryloxypropyl terminated mono-n-butyl terminated
polydimethylsiloxane, "mPDMS", about 24 wt. %
N,N-dimethylacrylamide, "DMA", about 6 wt. % 2-hydroxyethyl
methacryate, "HEMA", about 1.5 wt %
tetraethyleneglycoldimethacrylate, "TEGDMA", about 7 wt. %
polyvinylpyrrolidone, "K-90 PVP"; with the balance comprising minor
amounts of additives and photoinitiators. The polymerization is
most preferably conducted in the presence of about 23% (weight % of
the combined monomers and diluent blend) 3,7-dimethyl-3-octanol
diluent.
[0098] In a second preferred embodiment the reactive components
comprise about 30 wt. % SiGMA, about 23 wt. % mPDMS, about 31 wt %
DMA, about 0.5 to about 1 wt. % ethyleneglycoldimethacrylate,
"EGDMA", about 6 wt. % K-90 PVP; and about 7.5 wt % HEMA, with the
balance comprising minor amounts of additives and photoinitiators.
The polymerization is most preferably conducted in the presence of
tert-amyl-alcohol as a diluent comprising about 29 weight percent
of the reaction mixture. The diluent may also comprise about 11
weight % low molecular weight PVP (less than about 5,000 and
preferably less than about 3,000 M.sub.n.
[0099] In a third preferred embodiment, the reactive components
comprise about 11-18 wt % macromer (the GTP reaction product of
about 24 wt. % HEMA; about 3wt % MMA; about 33wt. %
methacryloxypropyltris(trimethylsiloxy)silane and about 32wt. %
mono-methacryloxypropyl terminated mono-butyl terminated
polydimethylsiloxane functionalized with 8 wt %
3-isopropenyl-.alpha.,.alpha.-dimethylbenzyl isocyanate); about
18-30 wt. % mPDMS, about 2-10 wt % acPDMS, about 27-33 wt. % DMA,
about 13-15 wt. % TRIS, about 2-5 wt. % HEMA, and about 5-7 wt. %
K-90 PVP; with the balance comprising minor amounts of additives
and photoinitiators. The polymerization is most preferably
conducted in the presence of 25-30% (weight % of the combined
monomers and diluent blend) a diluent comprising
3,7-dimethyl-3-octanol.
[0100] In a fourth preferred embodiment, the reactive components
comprise between about 15 to about 40 wt. % macromer (formed from
perfluoroether having a mean molecular weight of about 1030 g/mol
and .alpha., .omega.-hydroxypropyl-terminated polydimethylsiloxane
having a mean molecular weight of about 2000 g/mol, isophorone
diisocyanate and isocyanatoethyl methacrylate); about 40 to about
52% SiGMA, about 0 to about 5 wt %
3-tris(trimethylsiloxy)silylpropyl methacrylate, "TRIS", about 22
to about 32 wt. % DMA, about 3 about 8 wt % K-90 PVP with the
balance comprising minor amounts of additives and photoinitiators.
The polymerization is most preferably conducted in the presence of
about 15 to about 40, and preferably between about 20 and about 40%
(weight % of the combined monomers and diluent blend), diluent,
which may, in some emobodiments preferably be ethanol,
3,7-dimethyl-3-octanol.
Processing
[0101] The biomedical devices of the invention are prepared by
mixing the high molecular weight hydrophilic polymer, the
compatibilizing component, plus one or more of the following: the
oxygen permeability enhancing component, the hydrophilic monomers,
the additives ("reactive components"), and the diluents ("reaction
mixture"), with a polymerization initator and curing by appropriate
conditions to form a product that can be subsequently formed into
the appropriate shape by lathing, cutting and the like.
Alternatively, the reaction mixture may be placed in a mold and
subsequently cured into the appropriate article.
[0102] Various processes are known for curing the reaction mixture
in the production of contact lenses, including spincasting and
static casting. Spincasting methods are disclosed in U.S. Pat. Nos.
3,408,429 and 3,660,545, and static casting methods are disclosed
in U.S. Pat. Nos. 4,113,224 and 4,197,266. The preferred method for
producing contact lenses comprising the polymer of this invention
is by the direct molding of the silicone hydrogels, which is
economical, and enables precise control over the final shape of the
hydrated lens. For this method, the reaction mixture is placed in a
mold having the shape of the final desired silicone hydrogel, i.e.,
water-swollen polymer, and the reaction mixture is subjected to
conditions whereby the monomers polymerize, to thereby produce a
polymer/diluent mixture in the shape of the final desired product.
Then, this polymer/diluent mixture is treated with a solvent to
remove the diluent and ultimately replace it with water, producing
a silicone hydrogel having a final size and shape which are quite
similar to the size and shape of the original molded
polymer/diluent article. This method can be used to form contact
lenses and is further described in U.S. Pat. Nos. 4,495,313;
4,680,336; 4,889,664; and 5,039,459, incorporated herein by
reference.
Curing
[0103] Yet another feature of the present invention is a process
for curing silicone hydrogel formulations to provide enhanced
wettability. It has been found that the gel time for a silicone
hydrogel may be used to select cure conditions which provide a
wettable ophthalmic device, and specifically a contact lens. The
gel time is the time at which a crosslinked polymer network is
formed, resulting in the viscosity of the curing reaction mixture
approaching infinity and the reaction mixture becoming non-fluid.
The gel point occurs at a specific degree of conversion,
independent of reaction conditions, and therefore can be used as an
indicator of the rate of the reaction. It has been found that, for
a given reaction mixture, the gel time may be used to determine
cure conditions which impart desirable wettability. Thus, in a
process of the present invention, the reaction mixture is cured at
or above a gel time that provides improved wettability, or more
preferably sufficient wettability for the resulting device to be
used without a hydrophilic coating or surface treatment ("minimum
gel time"). Preferably improved wettability is a decrease in
advancing dynamic contact angle of at least 10% compared to
formulation with no high molecular weight polymer. Longer gel times
are preferred as they provide improved wettability and increased
processing flexibility.
[0104] Gel times will vary for different silicone hydrogel
formulations. Cure conditions also effect gel time. For example the
concentration of crosslinker will impact gel time, increasing
crosslinker concentrations decreases gel time. Increasing the
intensity of the radiation (for photopolymerization) or temperature
(for thermal polymerization), the efficiency of initiation (either
by selecting a more efficient initiator or irradiation source, or
an initiator which absorbs more strongly in the selected
irradiation range) will also decrease gel time. Temperature and
diluent type and concentration also effect gel time in ways
understood by those of skill in the art.
[0105] The minimum gel time may be determined by selecting a given
formulation, varying one of the above factors and measuring the gel
time and contact angles. The minimum gel time is the point above
which the resulting lens is generally wettable. Below the minimum
gel time the lens is generally not wettable. For a contact lens
"generally wettable" is a lens which displays an advancing dynamic
contact angle of less than about 70 and preferably less than about
60.degree. or a contact lens which displays a tear film break up
time equal to or better than an ACUVUE.RTM. lens. Thus, those of
skill in the art will appreciate that minimum gel point as defined
herein may be a range, taking into consideration statistical
experimental variability.
[0106] In certain embodiments using visible light irradiation
minimum gel times of at least about 30, preferably greater than
about 35, and more preferably greater than about 40 seconds have
been found to be advantageous.
[0107] Curing may be conducted using heat, ionizing or actinic
radiation, for example electron beams, Xrays, UV or visible light,
ie. electromagnetic radiation or particle radiation having a
wavelength in the range of from about 150 to about 800 nm.
Preferable radiation sources include UV or visible light having a
wavelength of about 250 to about 700 nm. Suitable radiation sources
include UV lamps, fluorescent lamps, incandescent lamps, mercury
vapor lamps, and sunlight. In embodiments where a UV absorbing
compound is included in the reaction mixture (for example, as a UV
block or photochromic) curing is conducting by means other than UV
irradiation (such as by visible light or heat). In a preferred
embodiment the radiation source is selected from UVA (about
315-about 400 nm), UVB (about 280-about 315) or visible light
(about 400-about 450 nm). In another preferred embodiment, the
reaction mixture includes a UV absorbing compound, is cured using
visible light. In many embodiments it will be useful to cure the
reaction mixture at low intensity to achieve the desired minimum
gel time. As used herein the term "low intensity" means those
between about 0.1 mW/cm.sup.2 to about 6 mW/cm.sup.2 and preferably
between about 1 mW/cm.sup.2 and 3 mW/cm.sup.2. The cure time is
long, generally more than about 1 minute and preferably between
about 1 and about 60 minutes and still more preferably between
about 1 and about 30 minutes This slow, low intensity cure is one
way to provide the desired minimum gel times and produce ophthalmic
devices which display good wettability.
[0108] Initiator concentration also effects gel time. Accordingly,
in some embodiments it is preferred to have relatively low amounts
of photoinitiator, generally 1% or less and preferably 0.5% or
less.
[0109] The temperature at which the reaction mixture is cured is
also important. As the temperature is increased above ambient the
haze of the resulting polymer decreases. Temperatures effective to
reduce haze include temperatures at which the haze for the
resulting lens is decreased by at least about 20% as compared to a
lens of the same composition made at 25.degree. C. Thus, suitable
cure temperatures include those greater than about 25.degree. C.,
preferably those between about 25.degree. C. and 70.degree. C. and
more preferably those between about 40.degree. C. and 70.degree. C.
The precise set of cure conditions (temperature, intensity and
time) will depend upon the components of lens material selected
and, with reference to the teaching herein, are within the skill of
one of ordinary skill in the art to determine. Cure may be
conducted in one or a muptiplicity of cure zones.
[0110] The cure conditions must be sufficient to form a polymer
network from the reaction mixture. The resulting polymer network is
swollen with the diluent and has the form of the mold cavity.
Deblocking
[0111] After the lenses have been cured they must be removed from
the mold. Unfortunately, the silicone components used in the lens
formulation render the finished lenses "sticky" and difficult to
release from the lens molds. Lenses can be deblocked (removed from
the mold half or tool supporting the lens) using a solvent, such as
an organic solvent. However, in one embodiment of the present
invention at least one low molecular weight hydrophilic polymer is
added to the reaction mixture, the reaction mixture is formed into
the desired article, cured and deblocked in water or an aqueous
solution comprising, consisting essentially of and consisting of a
small amount of surfactant. The low molecular weight hydrophilic
polymer can be any polymer having a structure as defined for a high
molecular weight polymer, but with a molecular weight such that the
low molecular weight hydrophilic polymer extracts or leaches from
the lens under deblocking conditions to assist in lens release from
the mold. Suitable molecular weights include those less than about
40,000 Daltons and preferably less than about 20,000 Daltons. Those
of skill in the art will appreciate that the foregoing molecular
weights are averages, and that some amount of material having a
molecular weight higher than the given averages may be suitable, so
long as the average molecular weight is within the specified range.
Preferably the low molecular weight polymer is selected from water
soluble polyamides, lactams and polyethylene glycols, and mixtures
thereof and more preferably poly-vinylpyrrolidone, polyethylene
glycols, poly 2 ethyl-2-oxazoline (available from Plymer Chemistry
Innovations, Tuscon, Ariz.), polymethacrylic acid, poly(1-lactic
acid), polycaprolactam, polycaprolactone, polycaprolactone diol,
polyvinyl alcohol, polyhema, polyacrylic acid, poly(1-glycerol
methacrylate), poly(2-ethyl-2-oxazoline), poly(2-hydroxypropyl
methacrylate), poly(2-vinylpyridine N-oxide), polyacrylamide,
polymethacrylamide and the like.
[0112] The low molecular weight hydrophilic polymer may be used in
amounts up to about 20 wt. % and preferably in amounts between
about 5 and about 20 wt % of the reactive components.
[0113] Suitable surfactants include non-ionic surfactants including
betaines, amine oxides, combinations thereof and the like. Examples
of suitable surfactants include TWEEN.RTM. (ICI), DOE 120
(Amerchol/Union Carbide and the like. The surfactants may be used
in amounts up to about 10,000 ppm, preferably between about 25 ppm
and about 1500 ppm and more preferably between about 100 and about
1200 ppm.
[0114] Suitable release agents are low molecular weight, and
include 1-methyl-4-piperidone, 3-morpholino-1,2-propanediol,
tetrahydro-2H-pyran-4-ol, glycerol formal, ethyl-4-oxo-1-piperidine
carboxylate, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone and
1-(2-hydroxyethyl)-2-pyrrolidone
[0115] Lenses made from reaction mixtures without low molecular
weight hydrophilic polymer may be deblocked in an aqueous solution
comprising at least one organic solvent. Suitable organic solvents
are hydrophobic, but miscible with water. Alcohols, ethers and the
like are suitable, more specifically primary alcohols and more
specifically isopropyl alcohol, DPMA, TPM, DPM, methanol, ethanol,
propanol and mixtures thereof being suitable examples.
[0116] Suitable deblocking temperatures range from about ambient to
about 100.degree. C., preferably between about 70.degree. C. and
95.degree. C., with higher temperatures providing quicker
deblocking times. Agitation, such as by sonication, may also be
used to decrease deblocking times. Other means known in the art,
such as vacuum nozzles may also be used to remove the lenses from
the molds.
Diluent Replacement/Hydration
[0117] Typically after curing the reaction mixture, the resulting
polymer is treated with a solvent to remove the diluent (if used),
unreacted components, byproducts, and the like and hydrate the
polymer to form the hydrogel. Alternatively, depending on the
solubility characteristics of the hydrogel's components, the
solvent initially used can be an organic liquid such as ethanol,
methanol, isopropanol, TPM, DPM, PEGs, PPGs, glycerol, mixtures
thereof, or a mixture of one or more such organic liquids with
water, followed by extraction with pure water (or physiological
saline). The organic liquid may also be used as a "pre-soak". After
demolding, lenses may be briefly soaked (times up to about 30
minutes, preferably between about 5 and about 30 minutes) in the
organic liquid or a mixture of organic liquid and water. After the
pre-soak, the lens may be further hydrated using aqueous extraction
solvents.
[0118] In some embodiments, the preferred process uses an
extraction solvent that is predominately water, preferably greater
than 90% water, more preferably greater than 97% water. Other
components may includes salts such as sodium chloride, sodium
borate boric acid, DPM, TPM, ethanol or isopropanol. Lenses are
generally released from the molds into this extraction solvent,
optionally with stirring or a continuous flow of the extraction
solvent over the lenses. This process can be conducted at
temperatures from 2 to 121.degree. C., preferably from 20 to
98.degree. C. The process can be conducted at elevated pressures,
particularly when using temperatures in excess of 100.degree. C.,
but is more typically conducted at ambient pressures. It is
possible to deblock the lenses into one solution (for example
containing some release aid) and then transfer them into another
(for example the final packing solution), although it may also be
possible to deblock the lenses into the same solution in which they
are packaged. The treatment of lenses with this extraction solvent
may be conducted for a period of from about 30 seconds to about 3
days, preferably between about 5 and about 30 minutes. The selected
hydration solution may additional comprise small amounts of
additives such as surfactants and/or release aids. Suitable
surfactants include include non-ionic surfactants, such as betaines
and amine oxides. Specific surfactants include TWEEN 80 (available
from Amerchol), DOE 120 (available from Union Carbide), Pluronics,
methyl cellulose, mixtures thereof and the like and may be added in
amounts between about 0.01 weight % and about 5% based upon total
weight of hydration solution used.
[0119] In one embodiment the lenses may be hydrated using a "step
down" method, where the solvent is replaced in steps over the
hydration process. Suitable step down processes have at least two,
at least three and in some embodiments at least four steps, where a
percentage of the solvent is replaced with water.
[0120] The silicone hydrogels after hydration of the polymers
preferably comprise about 10 to about 60 weight percent water, more
preferably about 20 to about 55 weight percent water, and most
preferably about 25 to about 50 weight percent water of the total
weight of the silicone hydrogel. Further details on the methods of
producing silicone hydrogel contact lenses are disclosed in U.S.
Pat. Nos. 4,495,313; 4,680,336; 4,889,664; and 5,039,459, which are
hereby incorporated by reference.
[0121] The cured biomedical device of the present invention
displays excellent resistance to fouling in vivo, even without a
coating. When the biomedical device is an ophthalmic device,
resistance to biofouling may be measured by measuring the amount of
surface deposits on the lens during the wear period, often referred
to as "lipid deposits".
[0122] Lens surface deposits are measured as follows: Lenses were
put on human eyes and evaluated after 30 minutes and one week of
wear using a slit lamp. During the evaluation the patient is asked
to blink several times and the lenses are manually "pushed" in
order to differentiate between deposits and back surface trapped
debris. Front and back surface deposits are graded as being
discrete (i.e. jelly bumps) or filmy. Front surface deposits give a
bright reflection while back surface deposits do not. Deposits are
differentiated from back surface trapped debris during a blink or a
push-up test. The deposits will move while the back surface trapped
debris will remain still. The deposits are graded into five
categories based upon the percentage of the lens surface which is
effected: none (<about 1%), slight (about 1 to about 5%), mild
(about 6% to about 15%), moderate (about 16% to about 25%) and
severe (greater than about 25%). A 10% difference between the
categories is considered clinically significant.
[0123] The ophthalmic devices of the present invention also display
low haze, good wettability and modulus.
[0124] Haze is measured by placing test lenses in saline in a clear
cell above a black background, illuminating from below with a fiber
optic lamp at an angle 66.degree. normal to the lens cell, and
capturing an image of the lens from above with a video camera. The
background-subtracted scattered light image was quantitatively
analyzed, by integrating over the central 10 mm of the lens, and
then compared to a -1.00 diopter CSI Thin Lens.RTM., which is
arbitrarily set at a haze value of 100, with no lens set as a haze
value of 0.
[0125] Wettability is measured by measuring the contact angle or
DCA, typically with borate buffered saline, using a Wilhelmy
balance at 23.degree. C. The wetting force between the lens surface
and borate buffered saline is measured using a Wilhelmy
microbalance while the sample is being immersed into or pulled out
of the saline. The following equation is used
F=2.gamma.p cos .theta. or .theta.=cos.sup.-1(F/2.gamma.p)
[0126] where F is the wetting force, y is the surface tension of
the probe liquid, p is the perimeter of the sample at the meniscus
and .theta. is the contact angle. Typically, two contact angles are
obtained from a dynamic wetting experiment--advancing contact angle
and receding contact angle. Advancing contact angle is obtained
from the portion of the wetting experiment where the sample is
being immersed into the probe liquid. At least 4 lenses of each
composition are measured and the values reported herein.
[0127] However, DCA is not always a good predictor of wettability
on eye. The pre-lens tear film non-invasive break-up time
(PLTF-NIBUT) is one measure of in vivo or "clinical" lens
wettability. The PLTF-NIBUT is measured using a slit lamp and a
circular fluorescent tearscope for noninvasive viewing of the
tearfilm (Keeler Tearscope Plus). The time elapsed between the eye
opening after a blink and the appearance of the first dark spot
within the tear film on the front surface of a contact lens is
recorded as PLTF-NIBUT. The
[0128] PLTF-NIBUT was measured 30-minutes after the lenses were
placed on eye and after one week. Three measurements were taken at
each time interval and were averaged into one reading. The
PLTF-NIBUT was measured on both eyes, beginning with the right eye
and then the left eye.
[0129] Movement is measured using the "push up" test. The patient's
eyes are in the primary gaze position. The push-up test is a gentle
digital push of the lens upwards using the lower lid. The
resistance of the lens to upward movement is judged and graded
according to the following scale: 1 (excessive, unacceptable
movement), 2 (moderate, but acceptable movement), 3 (optimal
movement), 4 (minimal, but acceptable movement), 5 (insufficient,
unacceptable movement).
[0130] The lenses of the present invention display moduli of at
least about 30 psi, preferably between about 30 and about 90 psi,
and more preferably between about 40 and about 70 psi. Modulus is
measured by using the crosshead of a constant rate of movement type
tensile testing machine equipped with a load cell that is lowered
to the initial gauge height. A suitable testing machine includes an
Instron model 1122. A dog-bone shaped sample having a 0.522 inch
length, 0.276 inch "ear" width and 0.213 inch "neck" width is
loaded into the grips and elongated at a constant rate of strain of
2 in/min. until it breaks. The initial gauge length of the sample
(Lo) and sample length at break (Lf) are measured. Twelve specimens
of each composition are measured and the average is reported.
Tensile modulus is measured at the initial linear portion of the
stress/strain curve.
[0131] The contact lenses prepared by this invention have O.sub.2
Dk values between about 40 and about 300 barrer, determined by the
polarographic method. Lenses are positioned on the sensor then
covered on the upper side with a mesh support. The lens is exposed
to an atmosphere of humified 2.1% O.sub.2. The oxygen that diffuses
through the lens is measured using a polarographic oxygen sensor
consisting of a 4 mm diameter gold cathode and a silver ring anode.
The reference values are those measured on commercially available
contact lenses using this method. Balafilcon A lenses available
from Bausch & Lomb give a measurement of approx. 79 barrer.
Etafilcon lenses give a measurement of 20 to 25 barrer. (1
barrer=10.sup.-10 (cm.sup.3 of gas.times.cm.sup.2)/(cm.sup.3 of
polymer.times.s.times.cm Hg).
[0132] Gel time was measured using the following method. The
photo-polymerization reaction was monitored with an ATS StressTech
rheometer equipped with a photo-curing accessory, which consists of
a temperature-controlled cell with a quartz lower plate and an
aluminum upper plate, and a radiation delivery system equipped with
a bandpass filter. The radiation, which originates at a Novacure
mercury arc lamp equipped with an iris and computer-controlled
shutter, was delivered to the quartz plate in the rheometer via a
liquid light guide. The filter was a 420 nm (20 nm FWHM) bandpass
filter, which simulates the light emitted from a TL03 bulb. The
intensity of the radiation, measured at the surface of the quartz
window with an IL1400A radiometer, was controlled to .+-.0.02
mW/cm2 with an iris. The temperature was controlled at
45.+-.0.1.degree. C. After approximately 1 mL of the de-gassed
reactive mixture was placed on the lower plate of the rheometer,
the 25 mm diameter upper plate was lowered to 0.500.+-.0.001 mm
above the lower plate, where it was held until after the reaction
reached the gel point.
[0133] The sample was allowed to reach thermal equilibrium
(.about.4 minutes, determined by the leveling-off of the steady
shear viscosity) before the lamp shutter was opened and the
reaction begun. During this time while the sample was reaching
thermal equilibrium, the sample chamber was purged with nitrogen
gas at a rate of 400 sccm. During the reaction the rheometer
continuously monitored the strain resulting from an applied dynamic
stress (fast oscillation mode), where time segments of less than a
complete cycle were used to calculate the strain at the applied
programmable stress. The computer calculated the dynamic shear
modulus (G'), loss modulus (G''), and viscosity (v*), as a function
of exposure time. As the reaction proceeded the shear modulus
increased from <1 Pa to >0.1 MPa, and tan .delta.(=G''/G')
dropped from near infinity to less than 1. For measurements made
herein the gel time is the time at which tan .delta. equals 1 (the
crossover point when G'=G''). At the time that G' reaches 100 Pa
(shortly after the gel point), the restriction on the upper plate
was removed so that the gap between the upper and lower plates can
change as the reactive monomer mix shrinks during cure.
[0134] It will be appreciated that all of the tests specified above
have a certain amount of inherent test error. Accordingly, results
reported herein are not to be taken as absolute numbers, but
numerical ranges based upon the precision of the particular
test.
[0135] In order to illustrate the invention the following examples
are included. These examples do not limit the invention. They are
meant only to suggest a method of practicing the invention. Those
knowledgeable in contact lenses as well as other specialties may
find other methods of practicing the invention. However, those
methods are deemed to be within the scope of this invention.
Examples
[0136] The following abbreviations are used in the examples below:
[0137] SiGMA 2-propenoic acid,
2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[trimethylsilyl)oxy]disilo-
xanyl]propoxy]propyl ester [0138] DMA N,N-dimethylacrylamide [0139]
HEMA 2-hydroxyethyl methacrylate [0140] mPDMS 800-1000 MW (M.sub.n)
monomethacryloxypropyl terminated mono-n-butyl terminated
polydimethylsiloxane [0141] Norbloc
2-(2'-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole [0142]
CGI 1850 1:1 (wgt) blend of 1-hydroxycyclohexyl phenyl ketone and
bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide
[0143] PVP poly(N-vinyl pyrrolidone) (K value 90) [0144] Blue HEMA
the reaction product of Reactive Blue 4 and HEMA, as described in
Example 4 of U.S. Pat. No. 5,944,853 [0145] IPA isopropyl alcohol
[0146] D3O 3,7-dimethyl-3-octanol [0147] mPDMS-OH
mono-(3-methacryloxy-2-hydroxypropyloxy)propyl terminated,
mono-butyl terminated polydimethylsiloxane (MW 1100) [0148] TEGDMA
tetraethyleneglycol dimethacrylate [0149] TrEGDMA triethyleneglycol
dimethacrylate [0150] TRIS
3-methacryloxypropyltris(trimethylsiloxy)silane [0151] MPD
3-methacryloxypropyl(pentamethyldisiloxane) [0152] MBM
3-methacryloxypropylbis(trimethylsiloxy)methylsilane [0153] AcPDMS
bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane
[0154] TRIS-HEMA 2-trimethylsiloxyethyl methacrylate [0155] MMA
methyl methacrylate [0156] THF tetrahydrofuran [0157] TBACB
tetrabutylammonium 3-chlorobenzoate [0158] TMI 3-isopropenyl-
-dimethylbenzyl isocyanate [0159] IPL isopropyl lactate [0160] CGI
819 2,4,6-trimethylbenzyldiphenyl phosphine oxide
[0161] Throughout the Examples intensity is measured using an IL
1400A radiometer, using an XRL 140A sensor.
Examples 1-10
[0162] The reaction components and diluent (D30) listed in Table 1
were mixed together with stirring or rolling for at least about 3
hours at 23.degree. C., until all components were dissolved. The
reactive components are reported as weight percent of all reactive
components and the diluent is weight percent of reaction mixture.
The reaction mixture was placed into thermoplastic contact lens
molds (made from Topas.RTM. copolymers of ethylene and norbornene
obtained from Ticona Polymers), and irradiated using Philips TL
20W/03T fluorescent bulbs at 45.degree. C. for about 20 minutes
N.sub.2. The molds were opened and lenses were extracted into a
50:50 (wt) solution of IPA and H.sub.2O, and soaked in IPA at
ambient temperature for about 15 hours to remove residual diluent
and monomers, placed into deionized H.sub.2O for about 30 minutes,
then equilibrated in borate buffered saline for at least about 24
hours and autoclaved at 122.degree. C. for 30 minutes. The
properties of the resulting lenses are shown in Table 1.
TABLE-US-00002 TABLE 1 EX. # Comp. 1 2 3 4 5 6 7 8 9 10 SiGMA 28 30
28.6 28 31 32 29 39.4 20 68 PVP (K90) 7 10 7.1 7 7 7 6 6.7 3 7 DMA
23.5 17 24.5 23.5 20 20 24 16.4 37 22 MPDMS 31 32 0 31 31 34 31
29.8 15 0 TRIS 0 0 0 0 0 0 0 0 15 0 HEMA 6 6 6.1 6 6.5 3 5.5 2.9 8
0 Norbloc 2 2 0 2.0 2 2 2 1.9 0 0 CGI 1850 0.98 1 1.02 1 1 1 1 1 1
0 TEGDMA 1.5 2 1.02 1.5 1.5 1 1.5 1.9 0 2 TrEGDMA 0 0 0 0 0 0 0 0 1
0 Blue HEMA 0.02 0 0 0 0 0 0 0 0 0 mPDMS-OH 0 0 31.6 0 0 0 0 0 0 0
Darocur 0 0 0 0 0 0 0 0 0 1 1173 D30 % 23 26 17 23 23 29 32 28 17
27 Properties % EWC.sup.1 36 33 39 40 36 37 39 25 48 29 Modulus 68
78 112 61 67 50 66 92 43 173 (psi) % Elongation 301 250 147 294 281
308 245 258 364 283 DCA.sup.2 62 55 58 64 72 65 61 55 92 72
(advancing) Dk.sup.3 103 111 101 131 110 132 106 140 64 76 (edge
corrected) .sup.1Equilibrium water content .sup.2Dynamic contact
angle, measured with physiological borate-buffered saline using a
Wilhelmy balance. .sup.3Oxygen permeability, edge corrected, in
Barrers.
[0163] The results of Examples 1-10 show that the reaction mixture
components and their amounts may be varied substantially, while
still providing uncoated lenses having an excellent balance of
mechanical properties and wettability. The contact angle (DCA) of
Example 9 may be too high to form a lens that would be clinically
wettable, and the modulus may be lower than desired to provide a
mechanically robust lens. Example 9 contained the lowest
concentration of SiGMA (20%). Because the SiGMA had been reduced,
less PVP could be added to the formulation and still provide a
compatible reaction mixture. Thus, these examples show that SiGMA
is effective in compatibilizing PVP and that when sufficient SiGMA
and PVP are present lenses with desirable wettability and other
mechanical properties can be made without any form of surface
modification.
Example 11
[0164] Lenses having the formulation of Example 1 were remade,
without controlling cure intensity. The mechanical properties are
reported in Table 2, below. These lenses were clinically evaluated
using ACUVUE.RTM. 2 lenses as controls. The test lenses were worn
in one eye and an ACUVUE.RTM.2 lens was worn on the contralateral
eye. The lenses were worn by 6 patients in a daily wear mode
(nightly removal) for a period of one week. At one week the
PLTF-NIBUT was 3.6 (.+-.3.0) seconds compared to 5.8 (.+-.2.5)
seconds for ACUVUE.RTM. 2 lenses. The front surface deposition was
graded none to slight for 50% of the test lenses and 100% for the
control lenses. The movement was acceptable for both test and
control lenses.
Example 12
[0165] Example 11 was repeated except that the cure intensity was
reduced to 1.0 mW/cm.sup.2. The mechanical properties are reported
in Table 2, below. These lenses were clinically evaluated using
ACUVUE.RTM. 2 lenses as controls. The test lenses were worn by 15
patients in a daily wear mode (nightly removal), in one eye for a
period of one week and an ACUVUE.RTM. 2 lens was worn in the
contralateral eye. At one week the PLTF-NIBUT was 8.2 (.+-.1.7)
seconds compared to 6.9 (.+-.1.5) seconds for ACUVUE.RTM. 2 lenses.
The front surface deposition was graded none to slight for all of
the patients for both test and control lenses. The movement was
acceptable for both test and control lenses.
TABLE-US-00003 TABLE 2 Ex.# 1 11 12 % EWC 36 36 36 Modulus (psi) 68
74 87 Elongation 301 315 223 DCA 62 77 56 Dk 103 127 102
[0166] Generally the mechanical properties for Examples 1, 11 and
12 are consistent results for multiple runs of the same material.
However, the clinical results for Examples 11 (uncontrolled cure
intensity) and 12 (low, controlled cure intensity) are
substantially different. The on eye wettability after one week of
wear for Example 11 (measured by PLTF-NIBUT) was worse that the
ACUVUE.RTM. 2 lenses (3.6 v. 5.8) and half the lenses had more than
slight surface depositions. The Example 12 lenses (controlled, low
intensity cure) displayed significantly improved on-eye
wettability, which was measurably better than ACUVUE.RTM. 2 lenses
(8.2 v. 6.9) and no surface depositions. Thus, using a low,
controlled cure provides an uncoated lens having on-eye wettability
which is as good as, and in some cases better than conventional
hydrogel lenses.
Examples 13-17
[0167] Reaction mixtures described in Table 3 and containing low or
no compatibilizing component (in these Examples SiGMA) were mixed
with constant stirring at room temperature for 16 hours. Even after
16 hours each of the reaction mixtures remained cloudy and some
contained precipitates. Accordingly, these reaction mixtures could
not be used to produce lenses.
TABLE-US-00004 TABLE 3 Ex. # Composition 13 14 15 16 17 SiGMA 0 0 0
10 20 PVP (K90) 12 12 10 8.0 8.0 DMA 10 10 8.3 19 19 MPDMS 37 37
30.8 35 28 TRIS 14 14 11.7 17 14 HEMA 25 25 37.5 8.0 8.0 Norbloc 0
0 0 0 0 CGI 1850 0 0 0 0 0 TEGDMA 1.0 1.0 0.83 2.0 2.0 TrEGDMA 0 0
0 0 0 Blue HEMA 0 0 0 0 0 mPDMS-OH 0 0 0 0 0 Darocur 1.0 1.0 0.83
1.0 1.0 1173 D30 % 23 31 31 27 27
[0168] Examples 13 through 15 show that reaction mixtures without
any compatibilizing component (SiGMA or mPDMS-OH) are incompatible,
and not suitable for making contact lenses. Examples 16 and 17 show
that concentrations of compatibilizing component less than about 20
weight % are insufficient to compatibilize signifincant amounts of
high molecular weight PVP. However, comparing Example 17 to Example
9, lesser amounts of high molecular weight PVP (3 weight %) can be
included and still form a compatible reaction mixture.
Examples 18-26
[0169] A solution of 1.00 gram of D3O, 1.00 gram of mPDMS and 1.00
gram of TRIS was placed in a glass vial (Ex. 18). As the blend was
rapidly stirred at about 20 to 23.degree. C. with a magnetic stir
bar, a solution of 12 parts (wt) PVP (K90) and 60 parts DMA was
added dropwise until the solution remained cloudy after 3 minutes
of stirring. The mass of the added DMA/PVP blend was determined in
grams and reported as the "monomer compatibility index". This test
was repeated using SiGMA (Ex. 19), MBM (Ex. 20), MPD (Ex. 21),
acPDMS, where n=10 (Ex. 22), acPDMS where n=20 (Ex. 23), iSiGMA-3Me
(Ex. 24) and TRIS2-HOEOP2 (Ex. 25) as test silicone monomers in
place of TRIS.
TABLE-US-00005 TABLE 4 Monomer Test silicone- compatibility Ex. #
containing monomer index Si:OH 18 SiGMA 1.8 3:1 19 TRIS 0.07 4:0 20
MBM 0.09 3:0 21 MPD 0.05 2:0 22 acPDMS (n = 10)* 1.9 11:2 23 acPDMS
(n = 20)* 1 21:2 24 ISiMAA-3Me 0.15 4:0 25 TRIS2-HOEOP2 0.11 3:2 26
MPDMS-OH 0.64 ~11:2 Doug - should we try mPDMS-OH and see what that
number is? Structures for acPDMS, iSiGMA-3Me and TRIS2-HOEOP2 are
shown below. acPDMS (n averages 10 or 20): ##STR00010##
TRIS2-HOEOP2 ##STR00011## iSiMAA3-Me ##STR00012##
[0170] The results, shown in Table 4, show that SiGMA, acPDMS
(where n=10 and 20) and mPDMS-OH more readily incorporate into a
blend of a diluent, another silicone containing monomer, a
hydrophilic monomer, and an high molecular weight polymer (PVP)
than alternative silicone-containing monomers. Thus,
compatibilizing silicone containing monomers having a compatibility
index of greater than about 0.5 are useful for compatibilizing high
molecular weight hydrophilic polymers like PVP.
Example 27-35
[0171] Lenses were made using the reaction mixture formulation of
Example 1. The plastic contact lens molds (made from Topas.RTM.
copolymers of ethylene and norbornene obtained from Ticona
Polymers) were stored overnight in nitrogen (<0.5% O.sub.2)
before use. Each mold was dosed with 75 .mu.l reaction mixture.
Molds were closed and lenses photocured using the times and cure
intensities indicated in Table 5. Lenses were formed by irradiation
of the monomer mix using visible light fluorescent bulbs, curing at
45.degree. C. The intensity was varied by using a variable balast
or light filters, in two steps of varied intensity and cure time.
The step 2 time was selected to provide the same total irradiation
energy (about 830 mJ/cm.sup.2) for each sample.
[0172] The finished lenses were demolded use a 60:40 mixture of
isopropyl alcohol/DI water. The lenses were transferred to a jar
containing 300 g 100% isopropyl alcohol (IPA). The IPA was replaced
every 2 hours for 10 hours. At the end of about 10 hours, 50% of
the IPA was removed and replaced with DI water and the jar was
rolled for 20 minutes. After 20 minutes, 50% of the IPA was removed
and replaced with DI water and the jar was rolled for another 20
minutes. The lenses were transferred to packing solution, rolled
for 20 minutes and then tested.
TABLE-US-00006 TABLE 5 Step 1 Step 1 Step 2 Step 2 Advancing
intensity time intensity time Contact Ex. # (mW/cm.sup.2) (min:sec)
(mW/cm.sup.2) (min:sec) Angle 27 1.1 6:55 5.5 1:28 51 .+-. 1 28 1.1
2:46 5.5 2:21 55 .+-. 2 29 1.1 11:03 5.5 0:35 55 .+-. 1 30 1.7 6:30
5.5 0:35 50 .+-. 1 31 1.7 1:37 5.5 2:21 55 .+-. 1 32 1.7 4:04 5.5
1:28 54 .+-. 2 33 2.4 2:52 5.5 1:28 62 .+-. 6 34 2.4 4:36 5.5 0:35
76 .+-. 9 35 2.4 1:09 5.5 0:35 78 .+-. 6
[0173] The contact angles for Examples 27 through 232 are not
significantly different, indicating that step 1 cure intensities of
less than about about 2 mW/cm.sup.2 provide improved wettability
for this lens formulation regardless of the step 1 cure time.
However, those of skill in the art will appreciate that shorter
step 1 cure times (such as those used in Examples 28 and 31) allow
for shorter overall cure cycles. Moreover, it should be noted that
even though the contact angles for Examples 33 through 35 are
measurably higher than those of Examples 27-32, the lenses of
Examples 33-35 may still provide desirable on eye wettability.
Examples 36-41
[0174] The reaction components of Example 1, were blended with
either 25% or 40% D3O as diluent in accordance with the procedure
of Example 1. The resultant reaction mixtures were charged into
plastic contact lens molds (made from Topas.RTM. copolymers of
ethylene and norbornene obtained from Ticona Polymers) and cured in
a glove box under a nitrogen atmosphere, at about 2.5 mW/cm.sup.2
intensity, about 30 minutes and the temperatures shown in Table 6,
below. The lenses were removed from the molds, hydrated and
autoclaved as describe in Example 1. After hydration the haze
values of the lenses were determined. The results shown in Table 6
show that the degree of haziness was reduced at the higher
temperatures. The results also show that as the concentration of
diluent decreases the haze also decreases.
TABLE-US-00007 TABLE 6 Ex. # % D30 Temp. (.degree. C.) % haze DCA
(.degree.) 36 25 25 30 (6) 99 37 25 50-55 12 (2) 100 38 25 60-65 14
(0.2) 59 39 40 25 50 (10) 68 40 40 50-55 40 (9) 72 41 40 60-65 32
(1) 66 *Haze (std. dev.)
[0175] The results in Table 6 show that haze may be reduced by
about 20% (Example 41 v. Example 39) and up to as much as about 65%
(Example 37 v. Example 36) by increasing the cure temperature.
Decreasing diluent concentration from 40 to 25% decrease haze by
between about 40 and 75%.
Examples 42-47
[0176] Lenses were made from the formulations shown in Table 8
using the procedure of Example 1, with a 30 minute cure time at
25.degree. C. and an intensity of about 2.5 mW/cm.sup.2. Percent
haze was measured and is reported in Table 7.
TABLE-US-00008 TABLE 7 Ex. # 42 43 44 45 46 47 SiGMA 28.0 28.0 28.0
28.0 28.0 28.0 mPDMS 31.0 31.0 28.0 28.0 28.0 28.0 acPDMS 0.0 0.0
4.0 4.0 4.0 4.0 (n = 10) DMA 23.5 23.5 23.5 23.5 24.0 24.0 HEMA 6.0
6.0 5.0 5.0 6.0 6.0 TEGDMA 1.5 1.5 1.5 1.5 0.0 0.0 Norbloc 2.0 2.0
2.0 2.0 2.0 2.0 PVP (K- 7.0 7.0 7.0 7.0 7.0 7.0 90) CGI 1850 1.0
1.0 1.0 1.0 1.0 1.0 D30 25.0 40 25.0 40.0 25.0 40.0 Properties Haze
30 50 7.3 14 26 25 Modulus 74 56 148 104 74 NT (psi) Elongation 326
395 188 251 312 NT (%) EWC (%) 38 41 33 35 38 39
[0177] A comparision of the results for formulations having the
same amount of diluent and either TEGDMA or acPDMS (Examples 42 and
46 and Examples 43 and 47) shows that acPDMS is an effective
crosslinker and provides lenses with properties which are
comparable to those where TEGDMA is used as a crosslinker. Examples
44 and 45 contain both crosslinkers. Haze for these Examples
decreased substantially compared to the lenses made from either
crosslinker alone. However, modulus and elongation were negatively
impacted (likely because the amount of crosslinker was too
great).
Examples 48-52
[0178] Reaction mixtures were made using the formulations shown in
Table 8 with a mixture of 72.5% t-amyl alcohol and 27.5% PVP
(M.sub.w=2500) as the diluent. The reaction mixtures were placed
into thermoplastic contact lens molds, and irradiated using Philips
TL 20W/03T fluorescent bulbs at 45.degree. C., 0.8 mW/cm.sup.2 for
about 32 minutes. The molds were opened and lenses were released
into deionized water at 95.degree. C. over a period of 20 minutes.
The lenses were then placed into borate buffered saline solution
for 60 minutes and autoclaved at 122.degree. C. and 30 minutes. The
properties of the resulting lenses are shown in Table 9.
TABLE-US-00009 TABLE 8 Ex. # Components 48 49 50 51 52 53 54 SiGMA
30 30 30 33 34 25 20 PVP 6 6 6 6 7 6 6 DMA 31 31 31 30 30 31 31
MPDMS 19 22 23.5 16.5 19 25 28 AcPDMS 2 0 0 3 0 0 0 (n = 10) HEMA
9.85 8.5 6.95 9 6 10.5 12.5 Norbloc 1.5 1.5 1.5 2 1.5 1.5 1.5 CGI
819 0.23 0.23 0.25 0.48 0 0.23 0.23 CGI 1850 0 0 0 0 1 0 0 EGDMA
0.4 0.75 0.8 0 0 0.75 0.75 TEGDMA 0 0 0 0 1.5 0 0 Blue HEMA 0.02
0.02 0 0 0 0.02 0.02 % Diluent* 40.0 40.0 27.3 39.4 25.9 40 40
Diluent comp A A B C D A A Properties EWC (%) 45 45 47 49 47 49 50
DCA 52 (2) 51 (7) 74 (10) 108 75 (6) 47 (2) 56 (11) (advancing)
Modulus (psi) 91 77 69 55 49 63 67 Elongation NT 232 167 275 254
110 124 (%) Dk (barrers) 54 60 78 44 87 59 60 Diluents (weight
parts): A = 72.5% t-amyl alcohol and 27.5 PVP (M.sub.W = 2500) B =
t-amyl alcohol C = 15/38/38% TMP/2M2P/PVP (M.sub.W = 2500) D =
57/43 2M2P/TMP NT--not tested
[0179] Thus, Examples 48, 51 show that formulations comprising both
hydrophilic (EGDMA or TEGDMA) and hydrophobic crosslinkers (acPDMS)
provide silicone hydrogel compositions which display an excellent
balance of properties including good water content, moderate Dk,
wettabiltiy, modulus and elongation.
Example 55
[0180] The lenses of Example 48 were clinically evaluated. The
lenses were worn by 18 patients in a daily wear mode (nightly
removal) for a period of one week. At one week the PLTF-NIBUT was
8.4 (.+-.2.9) seconds compared to 7.0 (.+-.1.3) seconds for
ACUVUE.RTM. 2 lenses. The front surface discrete deposition was
graded none to slight for 97% of the patients with the test lenses,
compared with 89% in control lenses. The movement was acceptable
for both test and control lenses.
Example 56
[0181] The lenses of Example 49 were clinically evaluated. The
lenses were worn by 18 patients in a daily wear mode (nightly
removal) for a period of one week. At one week the PLTF-NIBUT was
8.4 (.+-.2.9) seconds compared to 7 (.+-.1.3) seconds for
ACUVUE.RTM. 2 lenses. The front surface discrete deposition was
graded none to slight for 95% of the patients with the test lenses,
compared with 89% in control lenses. The movement was acceptable
for both test and control lenses.
Example 57
[0182] The lenses of Example 51 were clinically evaluated. The
lenses were worn by 13 patients in a daily wear mode (nightly
removal) for a period of one week. At one week the PLTF-NIBUT was
4.3 (.+-.1.9) seconds compared to 9.6 (.+-.2.1) seconds for
ACUVUE.RTM. 2 lenses. The front surface discrete deposition was
graded none to slight for 70% of the patients with the test lenses,
compared with 92% in control lenses. The movement was acceptable
for both test and control lenses. Thus, there is some correlation
between contact angle measurements (108.degree. for Example 51
versus 52.degree. for Example 48) and clinical wettability as
measure by PLTF-NIBUT (4.3 seconds for Example 51 versus 8.4
seconds for Example 48).
Examples 58-68
[0183] Silicone hydrogel lenses were made using the components
listed in Table 9 and the following procedure:
[0184] The components were mixed together in a jar to for a
reaction mixture. The jar containing the reaction mixture was
placed on a jar mill roller and rolled overnight.
[0185] The reaction mixture was placed in a vacuum desiccator and
the oxygen removed by applying vacuum for 40 minutes. The
desiccator was back filled with nitrogen. Contact lenses were
formed by adding approximately 0.10 g of the degassed lens material
to the concave front curve side of TOPAS.RTM. mold cavities in a
glove box with nitrogen purge. The molds were closed with
polypropylene convex base curve mold halves. Polymerization was
carried out under a nitrogen purge and was photoinitiated with 5 mW
cm.sup.2 of visible light generated using 20W fluorescent lights
with a TL-03 phosphor. After curing for 25 minutes at 45.degree.
C., the molds were opened. The concave front curve portion of the
lens mold was placed into a sonication bath (Aquasonic model 75D)
containing deionized water under the conditions (temperature and
amount of Tween) shown in Table 10. The lens deblock time is shown
in Table 10. The lenses were clear and of the proper shape to be
contact lenses.
TABLE-US-00010 TABLE 9 Ex. 58 Ex. 59 Ex. 60 Ex. 61 SiGMA 3.05 3.2
3.2 3.0 MPDMS 1.7 1.7 1.7 1.7 DMA 3.2 3.0 3.1 3.2 PVP 0.6 0.6 0.6
0.6 HEMA 1.0 0.8 0.8 1.0 TEGDMA 0.2 0.4 0.3 0.2 Norblock 0.15 0.2
0.2 0.2 1850 0.1 0.1 0.3 0.3 Triglide 1.5 1.5 1.5 2M2P 2.5 2.5 2.5
2.5 PVP low 0.5 1.5 1.5 0.5
TABLE-US-00011 TABLE 10 Form. Deblock time Ex. # Ex. # [Tween]
(ppm) Temp (.degree. C.) (min.) 62 58 850 75 10 63 58 10,000 70
10-15 64 58 0 75 20-22 65 58 850 22 10-15 66 59 850 85 3 67 60 850
85 6 68 61 850 75 18
Example 69
[0186] The lenses of Example 59 which were deblocked in Example 66,
were further hydrated in deionized water at 65.degree. C. for 20
minutes. The lenses were then transferred into borate buffered
saline solution and allowed to equilibrate for at least about 24
hours. The lenses were clear and of the proper shape to be contact
lenses. The lenses had a water content of 43%, a modulus of 87 psi,
an elongation of 175%, and a Dk of 61 barriers. The lenses were
found to have an advancing contact angle of 57 degrees. This
indicates the lenses were substantially free of hydrophobic
material.
Example 70
[0187] The concave front curve portion of the lens mold from
Example 61 was placed into a sonication bath (Aquasonic model 75D)
containing about 5% DOE-120 in deionized water at about 75.degree.
C. The lenses deblocked from the frame in 18 minutes.
Example 71
Use of an Organic Solvent
[0188] The concave front curve portion of the lens mold from
example 61 was placed into a sonication bath (Aquasonic 75D)
containing about 10% of 2-propanol an organic solvent in deionized
water at 75.degree. C. The lenses deblocked form the frame in 15
minutes. When Tween was used as the additive (Example 68) the
deblock time was 18 minutes. Thus, the present example shows that
organic solvents may also be used to deblock lenses comprising low
molecular weight hydrophilic polymers.
Example 72
Contains No Low Molecular Weight PVP
[0189] Silicone hydrogel lenses wee made using the formulation and
procedure of Example 58, but without any low molecular weight PVP.
The following procedure was used to deblock the lenses.
[0190] The concave front curve portion of the lens mold was placed
into a sonication bath (Aquasonic model 75D) containing about 850
ppm of Tween in deionized water at about 65.degree. C. The lenses
did not release from the mold. The deblock time for the formulation
which contained low molecular weight hydrophilic polymer (Example
58 formuation) under similar deblock conditions (Example 62-850 ppm
Tween and 75.degree. C.) was 10 minutes. Thus, the present Example
shows that deblocking cannot be accomplished in water only, in this
formulation without including low molecular weight hydrophilic
polymer in the formulation.
Example 73
[0191] The concave front curve portion of the lens mold from
example 72 was placed into a sonication bath (Aquasonic 75D)
containing about 10% of 2-propanol an organic solvent in deionized
water at 75.degree. C. The lenses deblocked form the frame in 20 to
25 minutes. Thus, lenses of the present invention which do not
contain low molecular weight hydrophilic polymer may be deblocked
using an aqueous solution comprising an organic solvent.
Examples 74-76
[0192] Formulations were made according to Example 49, but with
varying amounts of photoinitiator (0.23, 0.38 or 0.5 wt. %), curing
at 45.degree. C. with Philips TL 20W/03T fluorescent bulbs (which
closely match the spectral output of the visible light used to
measure gel time) irradiating the molds at 2.0 mW/cm.sup.2.
[0193] The advancing contact angles of the resulting lenses are
shown in Table 11.
TABLE-US-00012 TABLE 11 Ex. # Wt % Advancing DCA Gel time (sec) 74
0.23 59 (4) 65 75 0.38 62 (6) 57 76 0.5 80 (7) 51
Examples 77-79
[0194] Gel times were measured for the formulation of Example 1 at
45.degree. C. at 1.0, 2.5 and 5.0 mW/cm.sup.2. The results are
shown in Table 12.
TABLE-US-00013 TABLE 12 Intensity Ex. # (mW/cm.sup.2) gel time
(sec) 77 1 52 78 2.5 38 79 5 34
[0195] The results of Examples 74 through 76 and 77 through 79
compared with Examples 27-35, show that as gel times increase,
wettability improves. Thus, gel points can be used, in coordination
with contact angle measurements, to determine suitable cure
conditions for a given polymer formulation and photoinitiator
system.
Example 80
Macromer Preparation
[0196] To a dry container, which was housed in a dry box under
nitrogen at ambient temperature was added 30.0 g (0.277 mol) of
bis(dimethylamino)methylsilane (a water scavenger), a solution of
13.75 ml of a 1M solution of TBACB (386.0 g TBACB in 1000 ml dry
THF), 61.39 g (0.578 mol) of p-xylene, 154.28 g (1.541 mol) methyl
methacrylate (1.4 equivalents relative to initiator), 1892.13
(9.352 mol) 2-(trimethylsiloxy)ethyl methacrylate (8.5 equivalents
relative to initiator) and 4399.78 g (61.01 mol) of THF. This
mixture was charged to a dry, three-necked, round-bottomed flask
equipped with a thermocouple and condenser, all connected to a
nitrogen source.
[0197] The initial mixture was cooled to 15.degree. C. while
stirring and purging with nitrogen. After the solution reached
15.degree. C., 191.75 g (1.100 mol) of
1-trimethylsiloxy-1-methoxy-2-methylpropene (1 equivalent) was
injected into the reaction vessel. The reaction was allowed to
exotherm to approximately 62.degree. C. and then 30 ml of a 0.40 M
solution of 154.4 g TBACB in 11 ml of dry THF was metered in
throughout the remainder of the reaction. After the temperature of
reaction reached 30.degree. C. and the metering began, a solution
of 467.56 g (2.311 mol) 2-(trimethylsiloxy)ethyl methacrylate (2.1
equivalents relative to the initiator), 3636.6. g (3.463 mol)
n-butyl monomethacryloxypropyl-polydimethylsiloxane (3.2
equivalents relative to the initiator), 3673.84 g (8.689 mol) TRIS
(7.9 equivalents relative to the initiator) and 20.0 g
bis(dimethylamino)methylsilane was added.
[0198] This mixture was allowed to exotherm to approximately
38-42.degree. C. and then allowed to cool to 30.degree. C. At that
time, a solution of 10.0 g (0.076 mol)
bis(dimethylamino)methylsilane, 154.26 g (1.541 mol) methyl
methacrylate (1.4 equivalents relative to the initiator) and
1892.13 g (9.352 mol) 2-trimethylsiloxy)ethyl methacrylate (8.5
equivalents relative to the initiator) was added and the mixture
again allowed to exotherm to approximately 40.degree. C. The
reaction temperature dropped to approximately 30.degree. C. and 2
gallons of THF were added to decrease the viscosity. A solution of
439.69 g water, 740.6 g methanol and 8.8 g (0.068 mol)
dichloroacetic acid was added and the mixture refluxed for 4.5
hours to remove the trimethylsiloxy protecting groups on the HEMA.
Volatiles were then removed and toluene added to aid in removal of
the water until a vapor temperature of 110.degree. C. was reached.
The reaction flask was maintained at approximately 110.degree. C.
and a solution of 443 g (2.201 mol) TMI and 5.7 g (0.010 mol)
dibutyltin dilaurate were added. The mixture was reacted until the
isocyanate peak was gone by IR. The toluene was evaporated under
reduced pressure to yield an off-white, anhydrous, waxy reactive
macromer. The macromer was placed into acetone at a weight basis of
approximately 2:1 acetone to macromer. After 24 hrs, water was
added to precipitate out the macromer and the macromer was filtered
and dried using a vacuum oven between 45 and 60.degree. C. for
20-30 hrs.
Examples 81-88
[0199] Reaction mixtures were made in a nitrogen-filled glove box
using the formulations shown in Table 12 with a D3O and/or IPL as
the diluent. The reaction mixtures were placed into thermoplastic
contact lens molds, and irradiated using Philips TL 20W/03T
fluorescent bulbs at 50.degree. C., for about 60 minutes. The molds
were opened and lenses were released IPA, leached and transferred
into borate buffered saline. The properties of the resulting lenses
are shown in Table 13.
TABLE-US-00014 TABLE 13 Example Component 81 82 83 84 85 86 87 88
Macromer 18 18 13 13 13 13 13 11 MPDMS 23 18 29 28 28 28 26 28
AcPDMS 5 10 3 3 3 5 5 5 (n = 10) TRIS 14 14 15 15 15 14 13 14 DMA
27 27 28 29 30 30 33 32 HEMA 5 5 2 2 2 2 2 2 Norbloc 2 2 2 2 2 2 2
2 PVP K-90 5 5 7 6 5 5 5 5 Blue HEMA 0.02 0.02 0.02 0.02 0.02 0.02
0.02 0.02 CGI 1850 1 1 1 1 1 1 1 1 % Diluent 20 20 30 30 30 30 30
30 % D3O in dil. 60 60 100 100 100 60 100 100 % IPL in dil. 40 40 0
0 0 40 0 0 EWC (%) 36 32 40 40 39 37 40 38 DCA 48 46 45 50 57
(advancing) Modulus (psi) 149 268 85 90 91 107 134 129 Elongation
216 149 294 300 290 251 176 209 (%) Dk (barrers) 89 76 114 100 116
117
Example 89
[0200] The lenses of Example 83 were clinically evaluated. The
lenses were worn by 10 patients in a daily wear mode (nightly
removal) for a period of 30 minutes. For each patient, the test
lens was worn in one eye and an Bauch & Lomb Purevision lens
was worn in the contralateral eye. At thirty minutes the PLTF-NIBUT
was 7.5 (.+-.1.6) seconds compared to 8.6 (+1.6) seconds for the
Bausch & Lomb Purevision lens. The front surface discrete
deposition was graded none to slight for 100% of the patients with
the test lenses, compared with 100% in control lenses. The movement
was acceptable for both test and control lenses. The lenses of the
present invention are comparable in performance to the B&L
lens, which has a plasma coating. Thus, the present Example shows
that lenses formed from a polymer network comprising a siloxane
containing macromer, high molecular weight hydrophilic polymer and
a compatibilizing component display good wettability and deposition
resistance without a coating.
Example 90
[0201] Trifluoromethane sulfonic acid (2.3 ml) was added to 27.8 g
1,3-bis(hydroxybutyl)tetramethyldisiloxane and 204.4 g
octamethylcyclotetrasiloxane. The resulting solution was stirred
overnight. 17.0 g Na.sub.2CO.sub.3 were added and the mixture was
stirred for one hour. About 50 ml hexane was added and the mixture
was stirred for about one hour, then filtered. The hexane was
evaporated under reduced pressure and cyclics were removed by
heating to 110.degree. C. at <1 mBar for about one hour to
produce hydroxybutyl terminated polydimethylsiloxane.
[0202] In a separate flask 12.2 g CH.sub.2OH terminated
Fluorolink.RTM. Polymer
[0203] Modifier D10 with an average equivalent weight of 500
(Ausimont USA, equivalent to Fomblin.RTM. ZDOL) was combined with
11.8 mg dibutyltin dilaurate. The resulting solution was evacuated
to about 20 mBar twice, each time refilling with dry N.sub.2. 5.0
ml isophorone diisocyanate was added and the mixture was stirred
overnight under N.sub.2 to produce a clear viscous product.
[0204] 47.7 g of the hydroxybutyl terminated polydimethylsiloxane
from above was combined with 41.3 grams anhydrous toluene. This
solution was combined with the Fluorolink.RTM.-Isophorone
diisocyanate product and the resulting mixture was stirred under
nitrogen overnight. The toluene was evaporated from the product
over about 5 hours at <1 mBar. 3.6 g 2-isocyanatoethyl
methacrylate was added and the resulting mixture was stirred under
N.sub.2 for four days to produce a slightly opaque viscous liquid
fluorosilicone macromer.
Example 91
[0205] 2.60 g of the fluorosilicone macromer made in Example 90 was
combined with 1.12 g ethanol, 1.04 g TRIS, 1.56 g DMA, 32 mg
Darocur 1173 to produce a slightly hazy blend containing 18%
diluent (ethanol). Contact lenses were made from this blend in
plastic molds (Topas) curing 30 minutes under fluorescent UV lamps
at room temperature in a N.sub.2 atmosphere. The molds were opened,
and the lenses released (deblocked) into ethanol. The lenses were
leached with CH.sub.2Cl.sub.2 and then IPA for about 30 minutes
each at room temperature, then placed into borate buffered saline
for about 2 hours and then autoclave at 121.degree. C. for 30
minutes. The resulting lenses were tacky to the touch and had a
tendency to stick to each other. The advancing DCA of these lenses
was measured and is shown in Table 14.
Example 92-88
[0206] Reaction mixtures were made using the reactive components
(amounts based upon reactive components) shown in Table 14 and D30
as a diluent. The amount of D3O is based upon the total amount of
reactive components and diluent. The reaction mixture and lenses
were made using procedure of Example 91. The resulting lenses were
slippery to the touch and did not stick to each other.
[0207] The advancing DCA of these lenses was measured and is shown
in
[0208] Table 14, below.
TABLE-US-00015 TABLE 14 Example Component (wt %) 92 93 94
Fluorosilicone macromer 49.7 28.5 19 TRIS 19.9 0 0 DMA 29.8 24.8
24.7 PVP (K90) 0 5 4.9 SiGMA 0 40.7 50.1 EGDMA 0 0.4 0.6 Darocur
1173 0.6 0.6 0.6 Diluent Ethanol D3O D3O % Diluent in final blend
18 18 18 Advancing DCA 132 (8) 69 (7) 59 (9)
[0209] Examples 92 through 94 clearly show that hydrophilic polymer
may be used to improve wettability. In these Examples contact
angles are reduced by up to about 50% (Example 93) and up to about
60% (Example 94). Compositons comprising higher amounts of
fluorosilicone macromer and hydrophilic polymer can also be made by
functionalizing the fluorosilicone macromer to include active
hydrogens.
Examples 95-95
[0210] Reaction mixtures were made using reactive components shown
in
[0211] Table 15 and 29% (based upon all reactive components and
diluent) t-amyl alcohol as a diluent and 11% PVP 2,500 (based upon
reactive components). Amounts indicated are based upon 100%
reactive components. The reaction mixtures were placed into
thermoplastic contact lens molds, and irradiated using Philips TL
20W/03T fluorescent bulb at 60.degree. C., 0.8 mW/cm.sup.2 for
about 30 minutes under nitrogen. The molds were opened and lenses
were released into deionized water at 95.degree. C. over a period
of 15 minutes. The lenses were then placed into borate buffered
saline solution for 60 minutes and autoclaved at 122.degree. C. for
30 min. The properties of the resulting lenses are shown in Table
15.
TABLE-US-00016 TABLE 15 Ex. # Components 95 96 97 98 99 SiGMA 30 30
30 30 30 PVP 0 1 3 6 8 DMA 37 36 34 31 29 MPDMS 22 22 22 22 22 HEMA
8.5 8.5 8.5 8.5 8.5 Norbloc 1.5 1.5 1.5 1.5 1.5 CGI 819 0.25 0.25
0.25 0.25 0.25 EGDMA 0.75 0.75 0.75 0.75 0.75 Properties DCA 122
(8) 112 (6) 66 (13) 58 (8) 54 (3) (advancing) Haze 18 (4) 11 (1) 13
(1) 14 (2) 12 (1)
[0212] Table 15 shows that the addition of PVP dramatically
decreases contact angle. As little as 1% decreases the dynamic
contact angle by about 10% and as little as 3% decreases dynamic
contact angle by about 50%. These improvements are consistent with
those observed for macromer based polymers, such as those in
Examples 92-94.
Example 100
[0213] Preparation of mPDMS-OH (used in Examples 3)
[0214] 96 g of Gelest MCR-E11 (mono-(2,3-epoxypropyl)-propyl ether
terminated polydimethylsiloxane(1000 MW)), 11.6 g methacrylic acid,
0.10 g triethylamine and 0.02 g hydroquinone monomethylether were
combined and heated to 140.degree. C. with an air bubbler and with
stirring for 2.5 hours. The product was extracted with saturated
aqueous NaHCO.sub.3 and CH.sub.2Cl.sub.2. The CH.sub.2Cl.sub.2
layer was dried over Na.sub.e SO.sub.4 and evaporated to give 94 g
of product. HPLC/MS was consistent with desired structure:
##STR00013##
* * * * *