JPH04501924A - Non-irritating gas permeable soft contact lens and method for manufacturing the same - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Non-irritating gas permeable soft contact lens and method for manufacturing the same Background of the invention This application is based on the earlier application dated September 14, 1989, application serial number 407.263 and In a partial continuation application filed on December 14, 1987 with application serial number 132.174. be.

The present invention relates to contact lenses, and more particularly to contact lenses that are clinically acceptable. gas-permeable soft contact lenses based on silicone and their manufacture. Regarding the manufacturing method.

Development and use of plastic materials and compositions for contact lenses This is a subject that has received a great deal of attention over the years.

Among the first such developments was the rigid plastic polymethyl methacrylate There was a so-called hard lens using (PMMA). However, this material does not exhibit a sufficient degree of oxygen permeability and has very poor surface wetting properties. ing. Therefore, this technology is based on poly(2-hydroxyethyl methacrylate) progress towards softer lenses based on HEMA), and this material Has significantly improved oxygen permeability and surface quality than MMA plastics There is. However, these properties are still not as high as desired or necessary. and this type of lens often causes corneal stains, swelling, and ulcers. , caused serious problems such as enlargement and infection.

Recently, it has become better understood that the cornea requires intrinsic oxygen permeability. Based on this, two types of plastic materials, namely acrylic silicone and So-called gas-permeable hard materials made of either acrylic or acrylic fluorosilicone The use of (HGP) lenses has been proposed in the field. For example, U.S. Patent No. 3.80 See 8.178. Generally, the oxygen permeability of HGP lenses is determined by the silicon and and/or fluorosilicone, but At the same time, the surface wettability of this lens gradually deteriorated. To win, incorporate a relatively large amount of methacrylic acid, an ionic material, into the formulation. It is known that the surface of the lens becomes negatively charged as a result. This hand Although surface wettability can be improved by steps, this negatively charged surface is extremely have high absorbency, resulting in significant deposition problems. As a result, this HGP lenses have only limited possibilities.

More recently, polymerizable vinyl siloxanes and hydrophilic vinyl molybdenum hydrophilic gas-permeable soft polymer (SGP) based on compositions containing uttered. For example, US Patent Nos. 4.136.250; 4.139.513; 4, 182.822; 4.261.875; 4.343.927; 4.4 26.389; 4.486.577; 4.605.712; 4,711, 943; and 4.837.289. This kind of SGP lens has excellent acid It has elementary permeability and hydrophilicity. However, surprisingly, this lens Despite exhibiting high hydrophilicity, its functional (i.e. eye-related) wettability remains unmatched. relatively scarce, and this lens is very irritating and uncomfortable, The result is often severe deposit problems, which can lead to long-term use of this lens. making it extremely inappropriate to wear.

In the manufacture of early generations of soft contact lenses, the lenses were water-based or They were subjected to physiological saline extraction to make them clinically acceptable. example For example, U.S. Patent No. 4.158.089 (column line 6.25) and U.S. Pat. See number 3.937.680 (column 6.51 line). Very recently developed S GP lenses also cannot be subjected to such conventional treatment, i.e. extraction with physiological saline. has been done. For example, a lens into a methanol/water mixture of 50,150 v/v. U.S. Patent No. 4.139.513 (column line 9.16) involving immersion; No. 4.261.875 (column line 5.43) and U.S. Patent No. 4.711 ．． See 943 (column 37, line 32). In this type of processing, the present invention siloxane monomers and/or their low molecular weight derivatization occurring during polymerization. Based on the discovery that the body cannot be effectively dissolved and extracted There is. Therefore, prior art silicon-based SGP lenses have a substantial amount of residual siloxane monomers and derivatives, resulting in a high degree of irritation, poor wettability and serious deposition problems.

Silicone rubber lenses, as described in U.S. Patent No. 3.350.216 The use of hexane, a non-polar solvent, in the pretreatment of should be raised. However, hexane is not suitable for silicon-based SGP lenses. It was found to be unsuitable for use in extraction.

The main object of the present invention is to provide silicon-based SGP lenses as well as their manufacture. The objective of the present invention is to provide a method for manufacturing the lens material. residual monomers or other reactants and/or low molecular weight by-products of the polymerization reaction. demonstrated improved clinical acceptability by significantly reducing the levels of There is.

Summary of the invention For this and other purposes, conventional SGP lens materials, i.e. polymerizable vinyl-based The polymerization product of a composition containing a loxane monomer is molded into the shape of a lens. (e.g., lathe, cast molding, spin casting, etc.), and then the Instead of performing extraction using physiological saline, a hydrophilic polar group-containing organic solvent is used. Silicon-based SGP resins manufactured by extraction methods using This is achieved by providing After this organic solvent extraction step, this lens The lens is treated to exchange the organic solvent in the lens with saline.

Such treatment results in significantly reduced (preferably undetectable) levels of residual siloxane monomers or other low molecular weight derivatives resulting from polymerization reactions and therefore can be worn for long periods of time without irritation when using and without deposit problems. We believe that silicon-based SGP lenses can be manufactured using I found it.

detailed description of the invention With respect to the practice of the present invention, reference is made herein to the aforementioned patents, all of which are incorporated by reference. Conventional SGP lens materials based on silicon are used, as listed in .

Therefore, the silicon-based SGP lenses, for example, include at least one polymerizable vinyl siloxane monomer. polymerization product of a composition containing a monomer and at least one hydrophilic vinyl monomer Manufactured from synthetic materials. The polymerizable vinyl siloxane monomer has at least one polymerizable vinyl groups such as acrylic, styrenyl or vinyl groups; and at least one polysiloxanyl group. Polymerizable vinyl Examples of loxane monomers are: (I): Methyl methacrylate di(trimethylsiloxy)silylpropyl-glyclate Serol ethyl C.B.

(II): γ-tris(trimethylsiloxy)silylpropyl methacrylate H8 ■ CH.

It is. Hydrophilic vinyl septamers suitable for use in SGP lens compositions is N, N-dimethylacrylamide, 2-hydroxyethyl methacrylate , glycerol methacrylate, etc.

Compositions and techniques for producing essentially SGP lenses, e.g. lathing, casting Molding and spin casting are specifically mentioned above, all of which are referred to here. All of the US patents are well known in the art and illustrated by way of example.

According to the invention, the SGP material in the form of a lens is then provided with a hydrophilic polar group-containing material. Extraction is performed using a mechanical solvent (hereinafter referred to as PGS). Polymerizable vinyl SGP produced by copolymerization of siloxane monomer and hydrophilic vinyl monomer Lenses (which are typically hydrated to a water content of about 30-75% by weight to form soft lenses) (forming lenses), the PGS extraction is preferably performed during this initial hydration I'll do it later.

PGS for use in the present invention can be selected from a wide range of materials, especially those The choice is based on availability, cost, and the particular silicon-containing SGP lens used. The degree of extraction can vary depending on the extraction capacity for specific residual components in the . Preferably, the selected PGS is alcohol (ROM),'r) (RCOR'), Fludehy F (RCII, Ester (RCOOR') , amide (RCONR' R or N-alkylpyrrolidone [wherein RSR' and R'' are the same or different and are alkyl or hydrogen as appropriate. Also preferably, the alkyl substituent is 01-C, which may be unsubstituted or substituted. s alkyl, particularly preferred PGS are the 01-C5 alcohols, the most Preferably, it is an impromptu tool. This PGS is one or more of these PGSs. It may be a mixture of. 5 in the extraction of silicon-based S,GP materials Based on the aforementioned findings regarding the ineffectiveness of methanol/water mixtures of 0.150 v/v. Therefore, it is generally preferred to use the PGS completely anhydrous. However, a For some PGSs and some SGP materials, the solvent is a mixture with water. even if it contains water as a minor component, or this mixture Effective extraction is obtained when the silicon monomers can effectively dissolve all the materials. There is a possibility that

The PGS extraction of the SGP lenses of the present invention preferably involves residual siloxane monomer or other low molecular weight by-products of the wage reaction are acceptably low and preferably undetectable. or, alternatively, for an effective period of time, preferably with stirring, to reduce the It is removed by Soxhlet extraction by immersing the lens in the solvent. Ru. Completion of this extraction is followed by gas chromatography analysis for residual irritants, e.g. residual monomer levels. (GC), or agar cytotoxicity test, i.e. to test negative cytotoxic response; This can be monitored by immersing the extracted lens in agar. In general, soaking method An extraction time of 20 to 40 hours is suitable for the method. soxhlet extraction unit When used, the extraction period can generally be substantially shortened. Extract if required You can also repeat. Preferably, this extraction is carried out at a temperature in the range of about 20°C to 60°C. It will be held in

After completing the extraction, the PGS in this lens is removed by solvent exchange or vacuum decompression. After drying the solvent in the lens with the solvent, recondition the lens in physiological saline. It is necessary to replace it with physiological saline. After PGS extraction, this The SGP lens expands greatly, and the parameters of this lens are abnormally thick (becomes They discovered that the strength of this lens was extremely weak. in this state For example, if this lens is handled with forceps or pressed down, Breaks easily. As a result, the practice of PGS extraction is generally considered totally unacceptable. This particularly weak strength could theoretically be due to mechanical expansion. This is because it was thought to be due to irreversible rupture of the bond between the materials. However, after extraction Gluttle handling was found. In other words, PGS in the lens is When forceps are used to transfer or handle lenses after saline replacement By preventing mechanical force from being applied to the lens, it is possible to In particular, we found that the strength of this lens and its parameters were restored. did.

Lenses manufactured in this way are free of any detectable residual irritants. does not contain any residual silicone monomer and does not exhibit any cytotoxic response. do not have. Clinically, lenses manufactured in this way do not cause any irritation to the eye. Not shown. This lens is extremely comfortable and can be worn for long periods of time without deposit problems. can be done.

While not wishing to be limited in scope by any theory, the present invention The inherently improved comfort and wearability of more manufactured lenses means less residual silage. Xane monomers and/or derivatives generated during the polymerization reaction are removed from the lens. essentially extracted and removed, thereby making the SGP resin produced in a conventional manner lenses (in this regard, the above residues are leached onto the lens surface during use and have a negative impact on lens wettability, comfort and therefore lead to deposit problems and lens wear. This eliminates the problem of having a negative impact on wearability.

The invention will be further illustrated and described with reference to the following examples.

Example Manufactured according to the formulation and operation set forth in U.S. Patent No. 4.182.822. (This starting formulation contains 0.3% by weight of t-butyl peroxide as a catalyst.) Along with oxypivalate, 36% by weight of gamma-tris(trimethyl)methacrylate siloxy)silylpropyl (prepared according to Example 1 of the above-mentioned patent), 44 wt. % N, N-dimethylacrylamide (NNDMA, hydrophilic heptamer) and Consisting of 20% by weight 2-hydroxyethyl methacrylate (HEMA) ), an SGP lens was manufactured. This formulation was placed in a Teflon tube.

After deoxygenating with nitrogen for 15 minutes, the tube was sealed and the formulation was incubated at 40°C for 6 hours. After polymerization in a water bath, the mixture was further treated at 100° C. for 6 hours. Cut from this bar The button-shaped article was post-cured at 110°C for 44 hours under high vacuum (0.5 Torr). . On the other hand, this lens can also be cast or spun, which is well known in the field. It can also be produced from the formulation by casting techniques.

After hydration, at 60°C for 6 hours, as is commonly done in the production of soft lenses. The lens was subjected to the usual method of extraction in saline. This extraction level The level of residual silicon heptamers from GC in lenses is generally about 0.2 to 0. ．． 5% by weight, and the level of hydrophilic monomers is about 0.02-0.4% by weight. Met. In the agar test method, this lens showed a cytotoxic response. For clinical evaluation This type of lens is highly irritating, uncomfortable, and clinically It was not very acceptable.

However, in a separate experiment, the hydrated lenses were independently 4 mL impregnated. After 18 hours of immersion in Patul (a hydrophilic polar group-containing solvent), another 4 mL of fresh water was added. Soaked again in fresh isopropanol for 6 hours. Then, open the Improper tool. by cantation and without applying any mechanical force to this lens. Replaced with physiological saline. Is it possible to use GC for lenses manufactured in this way? No residual monomer was detected and no cytotoxic response occurred in the agar test. Didn't show it.

In clinical evaluation, this lens does not show any irritation and is suitable for long-term wear. It was also very comfortable. The strength of this lens is also surprisingly He later recovered.

On the other hand, the SGP lens material of this example is made of, for example, acetone, methyl ethyl ketone. , methyl acetate, N,N-dimethylacetamide or N-methylpyrrolidone. can be extracted under similar conditions.

Although the invention has been described with reference to particularly preferred embodiments, it is possible to It is not intended to limit the scope of the invention to, to the contrary, the accompanying claims Substitutes, modifications, and equivalents included within the spirit and scope of the invention, limited to the extent that It is intended to cover the following.

! 53″″5. Q13-

Claims (11)

[Claims] 1. Contains polymerizable vinyl siloxane monomers and hydrophilic vinyl monomers Composition consists of lenticular lens material which is a polymerization product and extracted Essentially free of possible residual siloxane monomers and low molecular weight polymerization by-products clinically acceptable silicone-based hydrophilic gas-permeable soft tact lens. 2. After extracting the lens using a hydrophilic polar group-containing organic solvent, By treating with physiological saline to replace the organic solvent with physiological saline, The above lenses contain extractable residual siloxane monomer and low molecular weight polymerization byproducts. A contact lens according to claim 1, which is essentially free of substances. 3. The above lens material is γ-tris(trimethylsiloxy)silyl methacrylate. A contact lens according to claim 2, which is a polymerization product of a composition comprising propyl. . 4. Claim that the hydrophilic vinyl monomer is N,N-dimethylacrylamide Contact lenses according to range 3 of 5. The hydrophilic seed group-containing organic solvent may be an alcohol of the formula ROH or an alcohol of the formula RCOR. ' Ketones of formula RCHO, aldehydes of formula RCHO, esters of formula RCOOR', formula R Amides of CON'R'', N-alkylpyrrolidones, and mixtures thereof ( where R, R' and R'' are selected from alkyl and optionally hydrogen). A contact lens according to claim 2 selected from the group consisting of: 6. A contact lens according to claim 5, wherein the alkyl is C1-C5 alkyl. ns. 7. Claims wherein the hydrophilic organic solvent is a C1-C5 alcohol. Contact lenses according to 5. 8. Claim 7, wherein the hydrophilic polar group-containing organic solvent is isopropanol. Contact lenses to follow. 9. The hydrophilic oak group-containing organic solvent is C1-C5 alcohol, acetone, Methyl ethyl ketone, methyl acetate, N,N-dimethylacetamide, and N- A contact lens according to claim 5 selected from the group consisting of methylpyrrolidone. Z. 10. Claims wherein the hydrophilic polar group-containing organic solvent is a CI to C5 alcohol. Contact lenses according to Box 4. 11. Claim 4 wherein the hydrophilic polar group-containing organic solvent is isopropanol. Contact lenses according to.