NZ201382A - Soft contact lens from methacrylate copolymer comprising at least one fluorine-containing monomer - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number £01 38£ 201382 NO DRAWINGS Priority Date(s): Complete Soecification Filed: Class: '&3. f? P.

R 3 SEP 'lQ85 Publication Date: ...»-•••• P.O. Journal, No: NEW ZEALAND PATENTS ACT, 195 3 No: Date: 26 J\JL 1932 fiecerveo COMPLETE SPECIFICATION SOFT CONTACT LENS we HOYA LENS CORPORATION, a corporation organized under the laws of Japan, of 25, Kowada, Itsukaichimachi, Nishitama-gun, Tokyo, Japan f hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- 201382 1 This invention relates to a soft contact lens.

More particularly, it relates to a soft contact lens which n Gb CHt / is prepared from a monomer mixture containing ^fcrifluoro- (P^s )tCH Gfehy 1 mothoarylato and/oi/(jiexafluoroisopropyy methacrylate 5 and is difficult to be deposited with tears or the like when used. Further, it relates to a soft contact lens having excellent mechanical strength and elasticity, and can sufficiently stably retain its lens shape even when processed into a thin lens.

In recent years, soft contact lenses (herein after abbreviated as "soft lenses") have come to be widely used in place of conventional hard contact lenses because of their comfortability of wearing. Most soft (nartAcfuUfe lenses are composed mainly of 2-hydroxyethyl methcarylatc 15 (HEMA) or N-vinylpyrrolidone (NVP), and have a water content of as a wide range as from about 20 to 85%.

Soft lenses vary in physical properties such as mechanical strength, refractive index, oxygen permeability, specific gravity and the like depending on the water 20 content of the materials. In general, with increase in the water content, the oxygen permeability increases, but the mechanical strength decreases. Further the refractive index and the specific gravity decrease and approach the value of water.

Since the materials for soft lenses are high in 2.01382 1 affinity for tears, the surfaces of the lenses are well wetted. Consequently, while soft lenses are used, resistance to soft lenses on the epithelium of a cornea and on the inner surface of an eyelid is reduced, so 5 wearers of soft lenses are relived of uncomfortableness due to the lenses as foreign bodies. Further, soft lenses permit, to a certain extent, the supply of oxygen to a cornea epithelium through their own materials, and hence have a function of relieving want of oxygen in a 10 cornea to some degree.

Increase in the water content of soft lenses leads to improvement of the wettability and oxygen permeability through the lenses, but results in lowering of the mechanical strength of the materials, so that the lenses 15 get easier to break while handled. As another method for supplying more oxygen to a cornea, there is a method by which soft lenses are made more thinner. This method is advantageous in that wearers of soft Lenses.are relieved of uncomfortableness due to the lenses as foreign 20 bodies. However, according to this method, the front side and the back side of the lenses are difficult to be distinguished from each, other when the lenses are handled, and the lenses are folded in two and the both halves adhere to each other when the lenses are handled, 25 so that the lenses are very inconvenient when attached to eyes.

As a general problem in soft lenses, there is a problem of contamination on the lenses. Contamination on soft lenses are due to the adhesion of proteins, lipids, 2.01382 1 mucoids and the like in tears; the denaturation, precipitation and adhesion thereof by boiling; and the -adhesion of proteins, lipids and the like from fingers during handling of the lenses. The lenses stained there-5 with show white turbidity, color change to yellow and the like. Further, when the precipitated and adhered matters form a layer, the layer of these matters is cracked, so that the surface of the lenses becomes uneven. Consequently, the surface of the lenses becomes water-10 repellent and is lowered in oxygen permeability, so that the comfortableness to wearing is deteriorated. Further, the formation of said layer facilitates propagation of fungi, bacteria and the like. When soft lenses are seriously deposited, the effect of improving 15 visual acuity by the lenses is greatly lessened and the uncomfortableness due to the lenses as foreign bodies becomes very serious. The lenses sometimes become unusable. Further, the lenses sometimes cause cornea disease of their wearers and hence contamination is 20 a serious problem in soft lenses. As one mode of the employment of a soft lens, there is sometimes made an attempt to continuously wear a soft lens having a high water content in a patient after a cataract operation. However, in this case, since a material having a high 25 water content is used, a tear composition is apt to penetrate into the material, and the lens is liable to be contaminated because it cannot be washed everyday, which causes shortening of life of the lens. 2-01382 1 When contamination of soft lenses are caused by a tear composition, the contamination of the lenses vary depending upon the difference in composition of tears among wearers, but, in general, there is strong suspicion of the origin against proteins, particularly lysozyme present in tears. Further, mucoids, lipids and the like appear to adhere to the lysozymes complexly.

As a treatment for contaimination on soft lenses, there are now used a washing treatment with a cleaner and 10 a treatment with an enzymatic agent, however, in a sense, these are only passive countermeasures for removing deposit. Further, these treatments sometimes causes deposit on the lenses when the subsequent washing is insufficient.

In consideration of these facts, the present inventors have devoted themselves to studies to succeed in imparting deposit resistance to a material itself for a soft lens without deteriorating its physical properties, and to find that a soft lens obtained by using said 20 material retains its lens shape sufficiently even when its thickness is small, and is convenient for handling, whereby this invention has been accomplished.

That is to say, an object of this invention is to provide a soft lens to which proteins, lipids, 25 mucoids and the like from tears and the like hardly adhere.

Another object of this invention is to provide a soft lens which retains its lens shape sufficiently even 201382 when its thickness is small.

The soft lens of this invention is obtained by subjecting to casting polymerization, by a continuous-temperature-raising method from 35° to 110°C, a composition comprising 50 to 95? by weight of a monomethacrylate of an alkylene glycol, 5 to 35% by weight of CF3CH2(2,2,2-trifluoroethyl) methacrylate (hereinafter abbreviated as "TFEM") and/or (CF3)2CH (hexafluoroisopropyl) methacrylate (hereinafter abbreviated as "HFIPM"), and less than 40% by weight of one or more compounds selected from the group consisting of an unsaturated carboxylic acid having one or more carboxyl groups in the molecule, a monomethacrylate of a polyhydric alcohol having three or more hydroxyl groups, and an alkyl methacrylate; finishing the resulting polymer by usual mechanical processing and polishing to give thereto a lens shape; and then subjecting it to a hydration and swelling treatment involving an alkali treatment.

In one embodiment of the invention the unsaturated carboxylic acid having one or more carboxyl groups in the molecule is used in an amount of 11% by weight or less, the monomethacrylate of a polyhydric alcohol having three or more hydroxyl groups is used in an amount of 30% by weight or less, and the alkyl methacrylate is used in an amount of 10% by weight or less.

Since at least one fluorine-containing monomer such as TFEM or HFIPM is used in the soft lens of this invention, foreign matters adhere hardly to the surface of the soft lens, so that the soft lens is greatly reduced in color change to yellow and 6 201382 in white turbidity as compared with conventional soft lenses. Further, the lens can sufficiently retain its normal lens shape even when processed so as to be thinned, which is also a new property obtained by the addition of at least one fluorine-containing monomer such as TFEM and HFIPM. 2013 Ofi ■16 The production of a soft lens by use of a fluorine-containing acrylic or methacrylic ester has LfiUJ^S PlajnbttM- conventionally been known (jjonio Planfaack Jr.; Japanese Patent Appln. Kokai (Xaid-Open) 29,660/1978, U.S. Patent *t-,rwj7ofc i (flg 3022,710 (1-9770 ) , however this process uses a fluorine-containing ester whose ester moiety is a straight chain having 5 or more carbon atoms and uses no fluorine- containing ester whose ester moiety is short, such as TFEM and HFIPM used in this invention. "Is has been 10 confirmed that a hydroxyl group containing monomer and the fluorine-containing monomer used in the above-mentioned patent are poor in miscibility with each other and give only an opaque polymer by usual bulk polymerization, however TFEM and HFIPM used in this invention 15 give a transparent polymer: and lens without causing white turbidity and opaqueness, by bulk polymerization with the hydroxyl group containing monomer, which is a novel finding by present inventors. Further, unlike this invention, the above-mentioned patent does not aim at 20 obtaining a deposit-resistant soft lens. When at least one fluorine-containing monomer such as TFEM, HFIPM or the like is used as a copolymer component in this invention, a soft lens good in shape stability, elasticity and mechanical strength can be obtained even when 25 the thickness of the lens is small. Therefore, there could be obtained an ideal soft lens which advantageously supplies oxygen to the cornea of a lenswearer and gives only slight uncomfortableness due to the lens as a i - -% - 201382 1 foreign bodies.

It has become clear that as compared with conventional soft lenses containing no fluorine, the soft lens of this invention is reduced in deposit with proteins, lipids and mucoids. In particular, deposit with protein 125 was measured by use of lysozyme labeled with I to find a significant difference in adsorption of the lysozyme between the soft lens containing at least one fluorine-containing monomer of this invention 10 and a soft lens containing no fluorine and having the same water content as that of the soft lens of this invention. this invention was adjusted so as to be one-third of the 15 conventional thickness (about 0.05,mm in central thickness) , the lens retained its shape, and such a phenomenon that a piece of lens gets folded into two and sticked was not observed, and the lens gave no inconvenience for handling. This was an unexpected result, and was the 20 disconvery of a novel effect brought about by the employment of at least one fluorine-containing monomer. amount of 5 to 35% by weight. TFEM and HFIPM can be used alone or simultaneously. However, when the added amount 25 of the fluorine-containing monomer is less than 5% by weight, the effect of the monomer on antideposit is insufficient, and with, increase of the added amount, the effect on antideposit is heightened, but the elasticity Further, even when the thickness of the lens of The fluorine-containing monomer is used in an 201382 of the resulting soft lens is reduced. When the added amount exceeds 35% by weight, elasticity required of a soft lens becomes unobtainable. Suitably, an amount of 10 to 20% by weight is employed.

The monomethacrylate of an alkylene glycol is monomethacrylate of, for example, ethylene glycol, propylene glycol, diethylene glycol, tetraethylene glycol /Gon * 5 or a polyethylene glycol/, and is the main constituent of the soft lens of this invention. As the monomethacry- rfe) late, ethylene glycol monomethacrylate, i.e., 2- hydroxyethyl -mothoarylnto (2-HEMA) is preferably used. fvi g,li»a-CC Simultaneous use of 2-hydroxyethyl me. bhe amy la bo and propylene glycol -naonomuLliuai^late- is also preferred.

Representative examples of the unsaturated 15 carboxylic acids having one or more carboxyl groups in one molecule include acrylic acid, methacrylic acid, itaconic acid and the like, and the unsaturated carboxylic acid is a constituent for increasing the water content by a hydration and swelling treatment involving an 2 0 alkali treatment and imparting elasticity required for a soft lens. As the unsaturated carboxylic acid, methacrylic acid is particularly preferred.

As the monomethacrylate of a polyhydric alcohol having three or more hydroxyl groups, glyceryl 25 methacrylate or monomethacrylate of pentaerythritol is used, and this constituent contributes to the increase of the water content and the elasticity.

The preferred alkyl methacrylate is methyl, io -r- 201382 A 1 ethyl, n-propyl or n-butyl ester of methacrylic acid, and is a constituent for improving the strength, proces-sability and shape stability of the resulting soft lens.

In addition to these constituents, there may be 5 used, as cross linking agents, polyfunctional monomers such as ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, butylene glycol dimethacrylate, neopentyl glycol dimethacrylate, pro-10 pylene glycol dimethacrylate, diethylene glycol bisallyl-carbonate, trimethylolpropane trimethacrylate, bisphenol A dimethacrylate, methylenebisacrylamide, and the like. N-vinylpyrrolidone, acrylamide, methacrylamide or the like may be used as a constituent for increasing the 15 water content.

As the polymerization initiator, there are used conventional radical-generating agents, for example, benzoyl peroxide, lauroyl peroxide, cumene hydroperoxide, di-tert-butyl peroxide, bis-4-tert-butylcyclohexyl peroxy-20 dicarbonate, diisopropyl porojcydicarboanfao, az.obisisobutyro-\\ nitrile, azobisisovaleronitrile and the like, and initia- W\YV llkf awUJtiKL \\ r ^ tors generating a radical at) low temperature"^ 1 are more preferable. a>c A-o.^C o^jTfc fs Au^o^i * In this invention, the above-mentioned 25 constituents are mixed and then poured into a mold made of a metal, glass or plastics, after which in such a condition that the resulting mixture is hermetically sealed up, polymerization is completed in an electric ll -X- 201382 1 furnace by a continuous-temperature-raising method of from 3 5° to 110°C. After completion of the polymerization, the resulting polymer is taken out of the mold and finished by usual mechanical processing and finishing 5 to give thereto a lens shape. In order to hydrate and swell the finished lens, the lens is immersed in a physiological saline containing sodium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, and/or the like, at room temperature or with heating, and then 10 immersed in a physiological salt solution and allowed to stand at room temperature or heated while the physiological salt solution is renewed several times, to be hydrated and swollen. properties and elasticity as those of conventional soft lenses, and has such an effect of the addition of at least one fluorine-containing monomer that it is less susceptible to adhesion of deposit due to proteins, lipids and mucoids than conventional soft lenses.

Further, a soft lens retaining a lens shape sufficiently stably could be obtained even when the thickness of the soft lens was small. more detail referring to Examples and Comparative Examples, 25 which are not by way of limitation but by way of illustration. In Examples and Comparative Examples, parts are by weight.

The thus produced soft lens has the same optical This invention is further explained below in tl. 2-01382 1 Example 1 To a mixture of 89.7 parts of 2-hydroxyethyl methacrylate, 10 parts of TFEM and 0.3 part of methacry-lic acid was added 0.1 part of azobisisobutyronitrile 5 as a polymerization initiator, and the resulting mixture was sufficiently stirred and mixed, poured into a mold made of plastics, and then hermatically sealed up therein. The mixture was then subjected to polymerization in a continuous-temperature-raising furnace of 10 from 35° to 110°C, and the resulting transparent polymer was processed by cutting and polishing to give thereto a lens shape. The thus obtained lens was treated in a physiological saline containing 1.2% of sodium hydrogencarbonate at 80° to 90°C for 1 hour and then in a 15 physiological salt solution at 80° to 9Q°C for 1 hour, whereby the lens was allowed to absorb water and swell and at the same time, the unpolymerized monomer was eluted from the lens. The thus obtained soft lens had a water content of 3 5% and a tensile strength of 2 about 850 g/mm , was comfortable to wearing, and, as shown in Table 1, adsorbed only very small amount of protein (lysozyme) as compared with a conventional soft lens having the same water content, though it was equal in optical properties to the conventional soft 25 lens. Further, the soft lens, even when its thickness was made smaller, had the same shape stability as did those having a conventional thickness.

IS - yi - 2.01382 1 Example 2 To a mixture of 84 parts of 2-hydroxyethyl methacrylate, 15 parts of TFEM and 1 part of methacrylic acid was added 0.1 part of diisopropyl peroxydicarbonate, 5 and the same procedure as described in Example 1 was followed to obtain a soft lens having a water content of 36%. As shown in Table 1, this lens adsorbed only very small amount of the protein as compared with the conventional soft lens having the same water content and 10 containing no fluorine compound.

Example 3 methacrylate, 10 parts of TFEM and 20 parts of glyceryl methcarylate was added 0.1 part of bis-4-tert-butyl-15 cyclohexyl peroxydicarbonate, and polymerization and lens processing were carried out in the same manner as in ■ Example 1, after which the thus obtained lens was treated in a physiological salt solution at 80° to 90°C for 2 hours to produce a soft lens having a water content 20 of 36%. This soft lens had excellent resistance to deposit.

Examples 4 to 15 water contents were produced by the same technique as in 25 Examples 1 to 3. All the soft lenses were colorless and transparent, had the same optical properties, mechanical To a mixture of 70 parts of 2-hydroxyethyl Soft lenses having various compositions and 2.01382 1 processability and strength as those of conventional soft lenses, and were less susceptible to deposit with proteins. The soft lenses had good shape stability even when they were thin.

Comparative Examples 1 to 4 By the same technique as in Examples 1 to 3, soft lenses were produced from individual polymers having various compositions containing no fluorine-containing monomer, and were used as controls.

Each of the soft lenses obtained in above Examples and Comparative Examples was immersed in a solution of egg white lysozyme labeled with radioactive iodine 125 ( I) (concentration 500 ]ig/ml; pH 7.3; 0.05 M borate buffer), and taken out of the solution after 2.5 hours, 15 24 hours, 3 days and 10 days, and the lens surface-was washed with flowing water. Thereafter, the amount of egg white lysozyme adhered to the lens was measured by a method by which y-rays were detected by means of a well-type scintillation counter. As shown in Tables 1 to 4, 2 0 the amounts of lysozyme adhered to the lenses of the comparative examples 1 to 4 containing no fluorine-containing monomer as a copolymer component are taken as 100%, and those in the examples are shown in comparison therewith.

The shape stability is expressed .by (o) , o, A or x (explained below) based on the observation of the elasticity, ability to restore the original shape during - k- 201382 1 handling, and shape stability during handling of a thin lens (central thickness:0.05 mm). The tensile strength 2 is expressed in terms of g/mm . <§> o A x Greatly excellent shape stability and elasticity Excellent shape stability and elasticity A little inferior shape stability and elasticity Inferior shape stability and elasticity \(o X- Table 1 Sample Composition (parts by weight) Water content Adsorbed amount ratio Shape stability Tensile strength Immersion for 2.5 hs Immersion for 24 hs Immersion for 3 days Immersion for days Comparative Example 1 HEMA/EDMA (99/1) % 100% 100% 100% 100% A 250 Example 1 HEMA/TFEM/MA (89.7/10/0.3) % 84 65 57 60 © 850 2 HEMA/TFEM/MA (84/15/1) 36% 78 73 79 75 ® 910 3 HEMA/TFEM/GMA •(70/10/20) 36% 54 51 58 57 o 4 HEMA/TFEM/MA/MMA (84/10/1/5) 40% 81 68 83 85 @ 630 HEMA/TFEM/GMA/MMA (65/10/20/5) 38% 67 62 71 68 o 6 HEMA/HFIPM/MA (94/5/1) % 72 67 73 59 © 840 7 HEMA/HFIPM/GMA (60/10/30) 36% 53 48 56 61 o 8 HEMA/TFEM/MA/EDMA (88/10/1/1) 33% 70 62 65 71 @ 950 • <* « • # • Table 2 Sample Composition (parts by weight) Water content Adsorbed amount ratio Shape stability Tensile strength Immersion for 2.5 hs Immersion for 24 hs Immersion for 3 days Immersion for days Comparative Example 2 HEMA/MMA/EMA/MA (79/10/10/1) 40% 100% 100% 100% 100% A 430 Example 4 HEMA/TFEM/MMA/MA (84/10/5/1) 40 36 60 56 51 @ 630 9 HEMA/HFIPM/MMA/MA (73.5/15/10/1.5) 41 32 49 62 47 @ 650 HEMA/GMA/TFEM (60/30/10) 42 33 41 53 42 o 370 • V • • # • Table 3 Sample Composition (parts by weight) Water content Adsorbed amount ratio Shape stability Tensile strength Immersion for 2.5 hs Immersion for 24 hs Immersion for 3 days Immersion for days Comparative Example 3 HEMA/MMA/MA (80/15/5) 60% 100% 100% 100% 100% A 210 Example 11 HEMA/TFEM/MMA/MA (64.8/20/10/5.2) 60 39 48 50 39 © 440 12 HEMA/TFEM/MA (76/20/4) 60 46 62 45 © 400 13 HEMA/HFIPM/MA/MMA (69.7/15/5.3/10) 60 38 53 61 57 A

Claims (8)

• V • • # • Table 4 Sample Composition (parts by weight) Water content Adsorbed amount ratio Shape stability Tensile strength Immersion for 2.5 hs Immersion for 24 hs Immersion for 3 days Immersion for 10 days Comparative Example 4 HEMA/MA/n-BMA/MMA (77/10/3/10) 72% 100% 100% 100% 100% x 160 Example 14 hema/tfem/mma/ma/h^M (53/20/10/11/5/1) hl2 .44 58 71 70 o 300 15 HEMA/NVP/TFEM/EDMA (70/20/9/1) 70 40 51 63 61 o 270 Abbreviation: HEMA tfem HFIPM MA GMA MMA 2-hydroxyethyl methacrylate 0,*; 1- tri f 1 linrnrthyl- methacrylate ffliexafluoroisopropyiy methacrylate methacrylic acid glyceryl methacrylate methyl methacrylate EDMA ethylene glycol dimethacrylate EMA ethyl methacrylate 4G tetraethylene glycol dimethacrylate NVP N-vinylpyrrolidone HPMA 2-hydroxypropyl methacrylate n-BMA n-butyl methacrylate WHAT l/WE CLAIM IS; 2.0138 2 J

1. A soft contact lens obtained by subjecting^ to casting polymerization^by a continuous-temperature-raising method of from 35° to 110°C, a composition comprising 50 to 9 5% by weight of a monomethacrylate of an alkylene OKCi*, glycol, 5 to 35% by weight of tarafluoroothyl methacrylate and/or/Qiexafluoroisopropyy methacrylate, and less than 40% by weight of one or more compound selected from the group consisting of an unsaturated carboxylic acid having one or more carboxyl■groups in the molecule, a monomethacrylate of a polyhydric alcohol having three or more hydroxyl groups, and an alkyl methacrylate; mechanically processing and polishing the resulting polymer to give thereto a lens shape; and then hydrating and swelling the polymer.

2. A soft contact lens according to Claim 1, wherein the monomethacrylate of an alkylene glycol is monomethacrylate of ethylene glycol, propylene glycol, diethylene glycol, tetraethylene glycol or a polyethylene glycol [H0(CH2CH20)nH, n = 5 to 20],

3. A soft contact lens according to Claim 1 or 2, wherein the unsaturated carboxylic acid having one or more carboxylic groups in the molecule is selected from the group consisting of acrylic acid, methacrylic acid and itaconic acid.

4. A soft contact lens according to any of Claims 1 to 3, wherein the monomethacrylate of a polyhydric alcohol having three or more hydroxyl groups is glyceryl

K - yf- re- methacrylate or -moe^mtyfchaof^*<JCU of pentaerythritol. 5. A soft contact lens according to any of Claims 201382 g ffi mo»or.eH,acn(Wre % 1 to 4, wherein the alkyl methacrylate is selected from the group consisting of methyl, ethyl, n-propyl and n-butyl esters of methacrylic acid.

6. A soft contact lens according to any of Claims 1 to 5, wherein the unsaturated carboxylic acid having one or more carboxyl groups in the molecule is used in an amount of eleven per cent by weight or less.

7. A soft contact lens according to any of Claims 1 to 6, wherein the monomethacrylate of a polyhydric alcohol having three or more hydroxyl groups is used in an amount of thirty per cent by weight or less.

8. A soft contact lens according to any of Claims 1 to 1, wherein the alkyl methacrylate is used in an amount of ten per cent by weight or less. «■» » • PER C/LX AGENTS for 2^ £