JPH04501882A - Flexible gas permeable contact lenses with improved clinical performance - 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] Background of the Invention: Flexible Gas Permeable Contact Lenses with Improved Clinical Performance This application is filed under U.S. Patent Application No. 07/407.261 filed September 14, 1989. No.; U.S. Patent Application No. 07/132.174 filed December 14, 1987 ( This in turn is part of U.S. Patent Application No. 001.149, filed January 7, 1987. and U.S. Patent Application No. 07/3 filed July 18, 1989. This is a continuation-in-part application of No. 81,587.

The present invention relates to contact lenses, more particularly having improved clinical performance. , relating to hydrophilic flexible gas permeable contact lenses.

Some of the most important properties and requirements of contact lenses are permeability (commonly referred to as DK), and highly wettable and adhesion resistant is the surface of

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

The first such development included the hard plastic polymethyl methacrylate (P There are so-called hard lenses that utilize MMA). However, this material Does not exhibit any significant degree of oxygen permeability and has very poor surface wetting properties . This technology was then applied to 2-hydroxyethyl methacrylate (EMA) Advances have been made to flexible lenses based on It had excellent oxygen permeability and surface quality. Nevertheless, these characteristics are still not as high as desirable or necessary, and this type of Lenses often have serious problems with corneal staining, swelling, ulceration, thickening, and infection. occured.

Somewhat more recently, based on a better understanding of the corneal requirements for substantial oxygen permeability, this In the field, there are two types of plastic materials, acrylic silicone or So-called hard gas permeable, composed of either acrylic fluorosilicone (HGP) lenses were proposed. See, e.g., U.S. Patent No. 3.808.17 No. 8. Generally, the oxygen permeability of HGP lenses is determined by the silicone and/or or can be increased progressively as the amount of fluorosilicone increases. However, at the same time, the wettability of the lens surface becomes progressively worse.

To overcome this problem, relatively large amounts of methacrylic acid (MAA), ionic material, which is known to be mixed into the formulation and cause the surface of the lens to be negatively charged to some extent. It is. Although this measure does not improve the wettability of the surface, negatively charged surfaces are highly It has high absorbency, leading to serious adhesion problems. In the end, HGP may have been limited It merely has.

More recently, hydrophilic flexible gas permeable (SGP) lenses have been developed, e.g. composition containing a functional vinyl siloxane monomer and a hydrophilic vinyl monomer Developed based on objects. See, e.g., U.S. Pat. No. 4,136,250; National Patent No. 4,182.822, U.S. Patent No. 4.261.875, U.S. Patent No. No. 4,343,927, U.S. Pat. No. 4,426.389, U.S. Pat. No. 4,48 No. 6.577, U.S. Pat. No. 4.605.712, U.S. Pat. No. 4,711.94 No. 3 and U.S. Pat. No. 4,837,289. This type of SGP lens is approximately It has a moisture content of 25 to 75% by weight, and has excellent oxygen permeability and hydrophilicity. do.

However, it is surprising that the clinical performance of SGP lenses, e.g. Very poor wettability, adhesion resistance and/or comfort (i.e. on the eyes) , making such lenses unsuitable for long-term wear.

Thus, despite advances to date, only a high degree of oxygen permeability remains. However, it also has excellent clinical performance, such as functional wettability and adhesion resistance. SGP type, which exhibits resistance and comfort, thus making the lens suitable for long-term wear. Plastic contact lenses are still in demand.

Summary of the invention This and other objects are achieved by the present invention, in which polymerizable vinyl siloxane molecules It is composed of a polymerization product of a composition consisting of a hydrophilic vinyl monomer and a hydrophilic vinyl monomer. , has the required high DK, flexibility and rebound, and at the same time a high degree of clinical This makes SGP lenses suitable for long-term wear. a ratio of hydroxyacrylic monomer units to silicon monomer units sufficient to provide A flexible gas permeable contact lens having This is achieved by providing

Required hydroxyacrylic monomer units versus silicon units on the lens surface A sufficient proportion increases the hydroxyacrylic monomer units on the surface and/or Alternatively, this can be achieved by surface treatment to reduce silicon units. of the present invention In a preferred embodiment, the surface treatment includes polyhydric alcohol (polyhydric alcohol) on the lens surface. (all) and/or by reaction with bases or acids, or on the lens surface. for grafting, attaching or coating hydroxyacrylic monomer units to This is done by processing the lenses.

The present invention provides a method for providing or intentionally providing a hydrophilic surface on a hydrophobic lens. significantly different from the prior art implementation with respect to. In this way, silicone rubber, crosslinked hydrophobic lenses made from polysiloxanes, e.g., U.S. Pat. No. 3,228 ．． Those exemplified in No. 741 are known in the art. These sparse Water-based lenses are highly oxygen permeable, yet functionally wettable, adhesion resistant and comfortable extremely poor in vision and also exhibits puzzling recalcitrant lens syndrome. . In this field, the application of extremely thin coatings of hydrophilic polymers Therefore, it is not known to try to improve the functional wettability of such lenses. Ru. See, e.g., U.S. Patent No. 3.85,982, U.S. Patent No. 3.916.0 No. 33, U.S. Patent No. 3,925,178 and U.S. Patent No. 4°143.949 issue. Generally, these efforts have been unsuccessful in each case. one principle The reason is as follows. That is, silicone rubber is rather hard, and after all, Extremely thin (i.e., angstrom level) hydrophilic coatings are routinely used. is easily rubbed off during the cleaning cycle, so that the lens can be quickly reused. Poor wettability, poor adhesion resistance, characteristic of silicone rubber hydrophobic lenses, Demonstrates discomfort and unmanageable lens syndrome. Resist scrubbing, more It is impractical to provide a thick layer of hydrophilic polymer on the lens. because, The oxygen permeability of the lens is substantially reduced, and silicone rubber and thick hydrophilic Differences in the refractive index of polymer coatings can result in highly undesirable lenses. This is because it becomes something like that.

In the present invention, the lens itself contains a substantial amount of water (e.g., generally at least 25% by weight), and thus its surface is In contrast to cone rubber lenses, which are already highly hydrophilic and hydrophobic Provide a surface coating of a hydrophilic polymer as taught for plastic materials. There would be no need. In the present invention, surprisingly, the SGP lens Even with highly hydrophilic uses, they nevertheless still have poor clinical performance. very poor, and this problem has no significant clinical impact on the surface of the SGP lens. Provides a sufficient ratio of hydroxyacrylic units to silicone units to produce an improvement It has been discovered that this can be overcome.

Additionally, in contrast to hydrophobic silicone rubber lens treatments, hydrophilic monomer coatings The criteria used when improving the wettability of those lenses by In producing improved clinical performance in hydrophilic SGP lenses related to light It was discovered that there was no correlation. For example, for hydrophobic lenses, The wettability that can be wetted has been determined based on the contact angle (see, e.g., U.S. Pat. No. 4,143,949, column 7, lines 13-16), amide monomer (N-vinyl Coatings based on lupyrrolidone are very effective in improving wettability (See Examples 1-2 of the above patent). However, in contrast The hydrophilic SGP lens of the present invention and (with a preferred range of 05 to 108 mm) For mid-thickness monomers containing such amide groups are completely ineffective in improving the clinical performance of

Accordingly, the discoveries and teachings of the present invention make it possible to improve the wetting of hydrophobic silicone rubber lenses. Improvements in sexual performance are not derived from known practices and cannot be predicted. Ta.

Detailed description of the invention Based on silicone (basic teachings and formulations for the formation of SGP lenses) and techniques reflected in the aforementioned patents, the disclosures of which are incorporated herein by reference. As is known in this field.

SGP lenses contain at least one polymerizable vinyl siloxane (PVS) polymerization of a composition containing a monomer and at least one hydrophilic vinylic monomer formed from the product. The polymerizable vinyl siloxane monomer contains at least one polymerizable vinyl group, such as an acrylic, styrenyl or vinyl group, at least one polysiloxanyl group, and at least one polysiloxanyl group connecting these two groups. also contains one bond; thus, for example, Tris(trimethylsiloxy)silylbropyglycerol-ethylgamma-tris (trimethylsiloxy)silylpropyl methacrylate (also sometimes hereinafter TS (call it M) C.I.

CH.

Hydrophilic vinyl suitable for use in SGP lens compositions with PvS The thread picker is, for example, N, N-dimethylacrylamide (NNDMA), 2-hydroxyethyl methacrylate (HEMA), glyceryl methacrylate (GMΔ), N-vinylpyrrolidone, and the like.

The lenses themselves are manufactured using known techniques such as lathe cutting, cast molding, and rotational molding. It is formed.

As previously mentioned, SGP lenses made according to known formulations have high oxygen permeability. However, it shows inferior clinical performance. In the present invention, hydroxyacrylic mono (HAM) units, preferably HEMA and/or GMA units, versus Silic By increasing the ratio of light units at the lens surface, clinical performance can be substantially improved. It was discovered that it can be improved. When used here, the unit to be referred to is the number of structural monomer units or silicon atoms, and the overall copolymer structure It includes units as parts of.

A hydroxyacrylic monomer (RAM) suitable for the practice of the present invention corresponds to the formula do: H2C=CC=0 X During the ceremony, R is H or substituted or unsubstituted alkyl, such as methyl or CH, COO H, and Is X hydroxyalkyloxy, hydroxyalkylamine and hydroxy? is a group selected from the group consisting of: alkyl is substituted or unsubstituted; and preferably CICl11 alkyl, most preferably C7 and C3 alkyl selected from: and the hydroxy on the alkyl is selected from a single hydroxy (e.g. (as in 2-hydroxyethyl methacrylate) or multiple hydro xy (as in glyceryl methacrylate, for example). Illustrative and and preferred hydroxyacrylic monomers are: 1.2-hydroxy acrylic monomers. ethyl acrylate or methacrylate; 2. glyceryl acrylate or is methacrylate; 3. ethylene glycolide ethyl acrylate or methacrylate; rate, i.e. CHt=CRCOOCHt CHtOCHz CHtO H.

4. Glycerol glyceryl acrylate or methacrylate, i.e. CH z=CRCOOCHtCH (OH) CHt OCHt Cl1 (0 summer () -CHl-OH: 5, N-hydroxymethyl, N-methylacrylamide or methacrylamide ; 6, N-2-hydroxyethyl, N-methylacrylamide or methacrylamide Mid; 7, N-2,3-dihydroxypropyl, N-methylacrylamide or meth Acrylamide; 8. Acrylic acid, methacrylic acid or itaconic acid.

As mentioned above, the SGP lenses of the present invention can be made from known SGP lens compositions. After forming the lens, the lens is treated to form a layer of SGP lens on its surface. Improved clinical performance, e.g. functional wettability, adhesion resistance, dehydration resistance and Enough RAM units vs. silicon units to provide comfort (e.g. RAM units by increasing and/or decreasing silicon units).

One means of achieving the required surface ratio of HAM to silicon units is to The surface, preferably in a dehydrated state, has the formula R, (OH), where R1 is substituted or unsubstituted. Substituted alkyl, preferably C2-cs alkyl, where n is at least an integer of 2), such as glyceryl methacrylate, ethylene Reacts with glycol, glycerin, glycerin-glycerin, polyglycerin, etc. By letting. This reaction is preferably carried out in the presence of a base, e.g. sodium hydroxide. preferably at a concentration of 0.1 to 10 mol %, based on the polyol. or alternatively in the presence of an acid or acid-containing mixture, e.g. ethanol/sulfuric acid. This reaction is performed based on the physical properties of the base lens (e.g., strength, oxygen permeability, flexibility). (softness, rebound, etc.) are essentially unaffected. This anti The solution is to increase RAM units by transesterification and/or to increase the number of RAM units by transesterification and/or means to reduce silicon units by cleavage of siloxane bonds catalyzed by Figure.

Alternatively, the core lens is HAM, preferably 2-hydroxyethyl acrylate. or methacrylates for grafting, attachment or coating on lens surfaces. further processing to give the lens surface a sufficient ratio of RAM units to silicon units.

Grafting, adhering or coating may be caused by known radiation-induced reactions, e.g. , X-rays, gamma-rays and other electromagnetic radiation, such as radio frequencies, microwaves, etc. , carried out using reactions induced by electron beam radiation, e.g. reactions induced by ultraviolet, gamma, or electron radiation are preferred. Delicious.

Processing techniques that can be used in the practice of this invention are themselves well known in the art. For example, grafting, adhesion or coating, ultraviolet light, Curing with γ-rays or electron beams is described in U.S. Pat. Patent No. 3,854,982: Rotary casting or casting of lenses, curing by radiation ; or plasma processing techniques well known in the field, e.g. No. 3,925.178 and U.S. Pat. No. 4,143,949. beyond these The disclosure of the technology is incorporated herein by reference. In a preferred embodiment of the invention , surface treatment includes poly(hydroxyalkyl acrylate and / or methacrylate), more preferably poly(2-hydroxyethyl acrylate) methacrylates and/or methacrylates). to be accomplished.

The required sufficient RAM units on the lens surface to produce the desired clinical performance. The ratio of recon units will depend on the particular PvS and hydrophilic layer type used. will vary primarily depending on the amount of growth. However, a sufficient ratio in the surface layer The ratio at any ratio is greater than the ratio present in the body or core of the lens. It would be very expensive. Preferably, ■] the ratio of AM units to silicon units in the surface layer is (both are 0.5. Generally speaking, the higher the ratio, the better the clinical The better the optical performance is, and the thicker the treated surface, the better the lens wetting. Sexual endurance will be better. However, the treated layer can achieve the desired proportions of the lens. It cannot be made so thick that it is adversely affected. Acceptable vine surface treatment The degree of may be monitored based on clinical response, as illustrated in the Examples of the specification. can. Thus, based on the present disclosure, sufficient RAM units on the lens surface The ratio of silicon units to silicon units can be readily determined by those skilled in the art.

While not wishing to be bound by any theory, improvements in the clinical performance of lenses are likely to be small. At least in part, between the eye's delicate corneal wetting mechanism and the composition and structure of the lens surface. It is presumed that this occurs due to the establishment of compatibility. Inadequate ratio of RAM units to system having silicone units or containing silicone units too high on the surface; Known SGP lenses are hydrophobic to the spreading and binding of mucin on the lens surface. That's too much. Mucin is an excellent wetting agent used in the cornea. , and contains a certain ratio of hydrophilic to hydrophobic sites. R on the lens surface As the amount of AM units increases, more sites for hydrogen to combine with hydrophilic sites on the mucin increases, but the decrease in silicon surface units reduces the number of hydrophobic sites (and thus Improves the spread of mucin on the lens surface. Sufficient ratio of RAM units to series As a result of a preferred embodiment of the present invention resulting in a lens surface having con units , the lens surface conforms more closely to, and becomes receptive to, lacrimal mucin. . Eventually, mucin spreads better on the lens surface and binds to it, thus Provide improved clinical performance. Thus, the wetting angle of the lens is controlled relative to that of the corneal surface to obtain the best results of the present invention. Wear.

The invention is further illustrated by the following examples.

I made an SGP lens from a button. These buttons are described in U.S. Pat. No. 4,182, No. 822, the starting formulation was 36% ( gamma-tris(trimethylsiloxy) prepared according to Example 1 of the above patent (by weight) ) silylpropyl methacrylate) (TMS), 59% N,N-dimethylacrylate Rylamide (NNDMA), and 5% methyl methacrylate (MMA) and 0.3% t-butyl peroxybiparate as catalyst. 1 After deoxygenating with nitrogen for 5 min, the tube was sealed and the formulation was placed in a 40°C water bath for 6 h. Polymerization was then carried out at 100° C. for a further 6 hours. cut from the rod The buttons were post-cured at 110° C. under high vacuum (0.5 torr) for 6 hours.

The lenses can be made by lathe techniques known in the art. hydration The lens is placed in a physiological position for a sufficient period of time in the absence of substantial stimulation. Extracted and conditioned in saline.

Lenses made in this way are approximately 4 to It has a DK five times higher and contains about 50% water by weight, thus making it flexible, repellent, Has an elastic and highly hydrophilic lens surface. IIAMRAM on lens surface Units versus silicon units equals zero. Clinically, lenses are performance that makes it unsuitable for use, such as functional wettability, adhesion resistance and comfort. was inferior to

The formulation was composed of 36% TSM, 58% NNDMA and 6% HEMA. Providing 6% by weight of HEMA in the formulation, as shown, results in a high ↑ID! 1, elasticity, highly hydrophilic surface and a ratio equal to 0.15 , l'lA'Ml unit, resulting in a lens having a positional silicon unit, thus Improved clinical performance compared to control lenses, e.g. functional wettability, Resulting in an improved lens with wear resistance and comfort. Clinically, the lens It could be worn by test patients for up to several hours.

Similarly, the lens formulation was 36% TSM, 44% NNDMA and 20% TSM. % HEMA, using 20 wt. % HEMA, high DK , flexible, repellent, highly hydrophilic surface and a RAM unit with a ratio equal to 0°5. yielding lenses with phase-to-silicon units and thus even higher compared to control lenses. Further improved clinical performance, e.g. functional wettability, adhesion resistance and comfort resulting in an improved lens with Clinically, lenses were tested by patients for several days. Can be worn continuously up to It is not acceptable (it will be).

The RAM to silicon ratio can be adjusted by increasing the amount of HEMA in the composition. As the temperature increases further, TSM is sacrificed and the oxygen permeability of the lens decreases. and/or cause the formation of opaque materials. As shown in the following example, RAM Further increases in the silicon to silicon ratio can be achieved by surface treatment. Ru.

Example 2 A 20% HEMA coated lens made as in Example 1 was After hydration in physical saline, extraction in isopropanol for 24 hours and then Glycerin containing 1 mol% NaOH in the dry state [96% purity, Kolge Colgate Palmolive Co. ] by stirring for 30 minutes at 70°C. Lens after this treatment The strength of the water was not significantly affected. The resulting lenses were It could be used for long-term wear and tear for at least one week. long period on patient In clinical practice, lenses have been worn continuously for up to 3 months in at least some patients. was able to be worn. Thus, surface treatment substantially improved clinical performance. .

Example 3 Consisting of 47% (by weight) TSM, 45% NNDMA and 8% HEMA , 38% moisture, high DK, flexibility, highly hydrophilic lens surface and ca. SGP lenses with a ratio of RAM units to silicon units equal to 5 are suitable for long-term wear. was found to be inappropriate. Clinically, lenses produce poor visual field and discomfort. and encountered serious adhesion problems after less than 4 hours of wear. however, The same lens was dehydrated using glycerin reagent [9] containing 10 mol% NaOH. 6% purity, Colgate Palmolive Company oliveCo, )] by stirring for 2 hours at 70°C. , lenses were used for weekly extended wear during a 3-week study period in the same patient. can be seen, the field of view is stable, and there are no observable deposits. and demonstrated a liquid layer across the lens surface.

Example 4 After processing as described in Example 3, the lenses were subjected to photoelectron spectroscopy analysis (ESCA). According to an independent surface study (approximately 100 angstroms of surface layer), after treatment, about 18% silicon or about 30% siloxy group reduction and 62% to 65% An increase in overall carbon content is shown, where C in the CO group is from 10.5% to 12.5%. % and the C in the COOR group increased from 5.3% to 6.3%. It was done. The increase in CO and C00R indicates that transesterification of glycerin has occurred. , indicating the formation of glyceryl methacrylate. Silicon unit after processing and/or increase in glyceryl methacrylate units, as described above. Increasing the ratio of RAM units to silicon units substantially improves clinical performance. ( Note: ESCA data are averaged over treated surfaces at a depth of 100 angstroms. It is a value. Thus, the correct value at the surface is substantially higher than the value reported above. . ) Example 5 A non-hydrated optically polished lens button is described in U.S. Patent No. 4. 182゜822 According to 36% (by weight) TSM, 42% NNDMA and 22% HEMA and surface treated with glycerin as described in Example 3 here. did. Thoroughly hydrate the button with physiological saline and coat its surface with a number of A simulated cleaning cycle is run, with each cycle immersing the parent in tap water. This included 10 finger rubs followed by wetting in physiological saline. physiological salts The wettability of the surface to similar solutions is approximately 1 year after weekly extended wear. After 60 cleaning cycles equal to the service life, the actual They were qualitatively the same.

The surface of the untreated button was substantially treated with a physiological saline solution under the same test conditions. It was not wettable.

Although the invention has been described with respect to certain preferred embodiments, the invention has been described in terms of specific preferred embodiments. is not intended to be limited to the form, but on the contrary is defined by the appended claims. Including changes, modifications, and equivalent embodiments that fall within the spirit and scope of the invention. intend to.

Published May 13, 1991

Claims (1)

[Claims] 1. From a polymerizable vinyl siloxane monomer and a hydrophilic vinyl monomer It is composed of a polymerized product of a composition, and in its surface layer and in the lens body. A sufficiently higher ratio of hydroxyauryl monomer units to silicone is present unit, thus imparting an additional degree of clinical performance to contact lenses. hydrophilic flexible gas permeable material with high oxygen permeability, flexibility and rebound properties. Hyperactive contact lenses. 2. The sufficiently high ratio means that there is a sufficient ratio of hydroxyauryl in the surface layer. treating the surface of the lens to provide monomer units versus silicon units; The contact lens according to item 1 above, which is produced from the above. 3. The hydroxyacrylic is hydroxyalkyl acrylate and/or The contact lens according to item 2 above, which is methacrylate. 4. The above treatment is applied to the lens surface and the formula R1(OH)n (wherein R1 is substituted or unsubstituted) and n is an integer of at least 2) The contact lens according to item 3 above, comprising: 5. The polyol may be ethylene glycol, glycerin or a mixture thereof. The contact lens according to item 4 above, which is selected from the group consisting of: 6. The treatment causes hydroxyl aurate to form on the lens surface through a radiation-initiated reaction. 2. The contact lens according to item 2 above, which comprises reacting a lyle monomer. 7. Hydroxyauryl monomer is hydroxyalkyl acrylate and/or or methacrylate, the contact lens according to item 6 above. 8. The contact lens according to item 7 above, wherein the radiation is electromagnetic radiation. 9. The contact lens according to item 7 above, wherein the radiation is γ-rays or ultraviolet rays. Z. 10. The radiation is selected from the group consisting of electron beam, electrical discharge and radio frequency. The contact lens according to item 7 above. 11. The polymerizable vinyl siloxane monomer is γ-tris (trimethylsiloxane). silylpropyl methacrylate, and the hydrophilic vinyl monomer The contact lens according to item 3 above, wherein the mer is N,N-dimethylacrylamide. ns. 12. The hydroxyalkyl acrylate and/or methacrylate is Consists of 2-hydroxyethyl methacrylate and glyceryl methacrylate The contact lens according to item 3 above, selected from the group. 13. The polymerizable vinyl siloxane monomer is γ-tris (trimethylsiloxane). silylpropyl methacrylate, and the hydrophilic vinyl monomer The contact according to paragraph 12 above, wherein the mer is N,N-dimethylacrylamide. lens. 14. The treatment includes poly(hydroxyalkyl acrylate) on the lens surface. to produce a thin coating consisting essentially of The contact lens according to item 7 above. 15, the poly(hydroxyalkyl acrylate and/or methacrylate) g) is poly(2-hydroxyethyl acrylate and/or methacrylate) ), the contact lens according to item 14 above. 16. The treatment includes poly(hydroxyalkyl acrylate) on the lens surface. to produce a thin coating consisting essentially of The contact lens according to item 11 above. 17. The poly(hydroxyalkyl acrylate and/or methacrylate) g) is poly(2-hydroxyethyl acrylate and/or methacrylate) ), the contact lens according to item 16 above.