JP3280324B2 - Intraocular or contact lens products - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an intraocular lens or contact lens product.

[0002]

BACKGROUND OF THE INVENTION The following is known, for example, from U.S. Pat. No. 3,895,169.
That is, a non-hydrophilic acrylate resin, for example, poly (methyl methacrylate) is treated with an organic compound using a strong acid, for example, a hot mixture of sulfuric acid and sulfonic acid, to form a hydrophilic layer on the surface of these resins. Can be. The organic compound is an organic compound having at least two primary or secondary hydroxyl groups in free form or esterified by a weak acid. The following are also already generally known earlier. That is, various hydrolyzable non-hydrophilic polymers are converted to strong acids at high temperatures.
Although Ru can hydrophilized by himself, but the polymer is easily dissolved in the same time a thermal acid further hydrophilic layer on the surface is dissolved or in the washing water, so that this way a durable uniform thickness in the It is extremely difficult to form a surface hydrophilic layer. Although the organic compound having at least two hydroxyl groups causes cross-linking to stabilize the surface layer, it is difficult to form a uniform and extremely thin hydrophilic layer, particularly for a target having a more complicated shape. Because the thermal acid swells the polymer very quickly and dissolves the polymer.

[0003]

SUMMARY OF THE INVENTION These disadvantages can be overcome by a method that involves immersing the object in a heated strong acid containing a pre-dissolved electrolyte. The electrolyte by itself does not react with the polymer. The electrolyte, which is advantageously a salt of the acid used, inert and sufficiently soluble in the given medium, leads to a reduction and suppression of the swelling and solubility of the acrylate or methacrylate polymer in the acid used, and thus A uniform, dense and optionally thin tough hydrophilic surface layer is provided depending on the concentration and temperature of the electrolyte. Since the acid does not quickly permeate from the polymer in the depth direction of the object due to swelling, the acid is easy to wash. Another advantage is as follows. Dilute sulfuric acid or sulfonic acid, for example 50% sulfuric acid or sulfonic acid, can be used for favorable results. Dilute sulfuric acid or dilute sulfonic acid was not sufficiently active in previous procedures without the addition of salts. The addition of polyhydric alcohols or their esters is not necessary, especially for crosslinked polymers, they can be used additionally and separately. Only some of the very long macromolecules are hydrolyzed during slow swelling, and the rest of them remain in the hydrophobic phase.

Using non-crosslinked polymers, such as poly (methyl methacrylate), using low concentrations of electrolytes, followed by hot polyhydric alcohols or esters thereof, such as glycerol, esters thereof with organic acids, such as diacetin or triacetin, A thicker hydrophilic surface layer can be obtained by wetting in (vinyl alcohol) or the like.

In addition to the stable and sufficiently soluble salts of the acids used, it is possible to use, for example, alkali metal hydrogen sulphate dissolved in sulfuric acid and to use non-volatile acids which are at least as strong as the free acids used. Stable and sufficiently soluble salts of, for example, poly (ethylene sulfonic acid), p-toluenesulfonic acid, hydroxypropylsulfonic acid or propylsulfonic acid.

The hydrophilization reaction on polymer esters or nitriles of methacrylic acid and acrylic acid forms carboxyls or, in the case of nitriles, first forms amides, which are then partially or completely converted from carboxyls. The hydrolysis reaction that forms. This hydrolysis reaction can be achieved with partial or complete esterification using a polyhydric alcohol in which part of the alcoholic hydroxyl group remains free, but this is not always necessary. At the same time, cross-linking occurs, for example, by the contribution of both α-hydroxys of glycerol, which form an ester group by the carboxyls of two adjacent polymer chains, while the central β-hydroxy remains at least partially free. To cause this esterification to occur simultaneously with the hydrolysis, the polymer is treated with a mixture of a polyhydric primary or secondary alcohol and a strong acid, or the two reactions are roughly divided as appropriate to cause the hydrolysis first, Next, the target product, which has been subjected to surface hydrolysis while being wet with a strong acid, is immersed in hot polyhydric alcohol for a short time.

If desired, an acid which is weaker than the acid used for the hydrolysis is used, and the hydroxyl or primary or secondary polyhydric acid is used.
The hydric alcohol may be at least partially pre-esterified.

[0008] Strong acids capable of hydrolyzing ester or nitrile groups are, for example, certain organic sulfonic acids such as sulfuric acid or toluenesulfonic acid. In addition to sulfuric acid, phosphoric acid or a mixture of phosphoric acid and sulfuric acid can be used.
Suitable electrolytes are, for example, alkali sulfates or phosphates or mixtures thereof. In addition, nitric acid or hydrochloric acid can be used if volatility or oxidizing property is not required.

The method described above is made of poly (methyl methacrylate), especially when there is a risk of damaging epithelial tissue (corneal endothelium, etc.) during application, especially for intraocular lenses, contact lenses or their supporting members. It is particularly suitable for hydrophilizing surgical tools (eg, the tip of a surgical forceps).
In such cases, the hydrophilization can replace the lubricating solution of hydraulic acid.

[0010]

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a hydrophobic polymer containing a unit selected from the group consisting of (a) an ester of acrylic acid, an ester of methacrylic acid, a nitrile of acrylic acid, a nitrile of methacrylic acid and a combination thereof. And (b) a repeating unit:

Embedded image Wherein R is hydrogen or methyl, and A is hydrogen, an alkali metal or a polyhydric alcohol group having two or more primary and / or secondary hydroxyl groups. A relatively thin surface layer comprising an insoluble, inert, biocompatible hydrophilic polymer; a novel intraocular lens or contact lens product having good optical, geometric and mechanical properties. An intraocular lens or contact lens product wherein the hydrophilic layer and the hydrophobic core are chemically and / or integrally bonded.

[0011] Undesired reflections occurring on the optical portion of the intraocular lens surrounded by the aqueous humor can be eliminated by continuously changing the reflectivity of the surface layer of the lens. The reflectivity of the lens surface is practically the same as the reflectivity of the aqueous humor, and varies continuously as far as the reflectivity of poly (methyl methacrylate) is concerned.

A soft, highly hydrophilic, non-irritating surface is obtained on a hard (methyl methacrylate) contact lens without compromising the optical and mechanical properties of the hard contact lens.

[0013] A thick hydrophilic layer can be obtained by simply hydrolyzing crosslinked polymer esters of acrylic acid and methacrylic acid and nitriles without matting the surface. Using a non-crosslinked acid, a stable and relatively thick water-swellable layer uses a low concentration of electrolyte in the solution,
It can then be prepared by wetting with hot polyhydric alcohols or weakly volatile acids and their esters, for example ethylene glycol, propylene glycol, glycerol, diacetin, triacetin, poly (vinyl alcohol) and the like.

The objectives made from polyacrylate or polymethacrylate esters or nitriles are:
A short, continuous immersion in the same or different acid solution before or after neutralization and subsequent washing in the aforementioned acid bath forms a continuously strongly adhered hydrophilic layer. You. The hydrophilicity and swelling capacity of this layer gradually decreases as it enters the interior from the surface. A similar effect is
This can be achieved by always immersing continuously in a more dilute acid solution of the salt or by any combination of these.

[0015]

The invention is further, but not exclusively, described by the following examples. Example 1 The tip of a forceps made from poly (methyl methacrylate)
It was immersed in a warm saturated solution of sodium hydrogen sulfate of 94% sulfuric acid at a temperature of 110 ° C. for 20 seconds with a length of 15 mm. The forceps were then washed with water and further washed with a 5% solution of potassium carbonate at 50 ° C. for 4 hours. Finally, the forceps were thoroughly washed with room temperature physiological solution. A strongly swollen, soft hydrophilic layer of about 15.2 mm in length and about 0.1 mm thick was provided on the tip of the forceps having a low coefficient of friction in the water-swelled state.

Example 2 Optical Intensity + Made from Poly (methyl methacrylate)
Portable organ for intraocular lens with 18D (haptic (ha
ptics)) was immersed in a warm saturated solution of potassium hydrogen sulfate in 90% sulfuric acid at 100 ° C. for 30 seconds. Wash the lens with water, then
It was washed for 2 hours in a 5% aqueous solution of potassium carbonate at 50 ° C., and finally for 4 hours in a 1% aqueous solution of sodium hydrogen carbonate.
The haptic coated with the hydrophilic polymer surface did not damage or scratch the eye or corneal tissue when the intraocular lens was inserted into the eye.

Example 3 According to Example 1, the original amount of sodium hydrogen sulfate was reduced to 75%, 60% and 50%, respectively, and three solutions were prepared using the same amount of solution and the same concentration of acid. did. The thickness of the hydrophilic layer, which can be observed in the part stained with a 0.001% by weight aqueous solution of methylene blue in the swollen state (immersed in the acid solution washed overnight in water for 30 minutes), increased with decreasing sulfate concentration.

Example 4 The procedure described in Example 1 was repeated. However, the forceps removed from the hot acid solution were immediately immersed in glycerol heated to 110 ° C. for 20 seconds. A thicker and softer hydrophilic layer that adhered well to the substrate was obtained.

Example 5 A plate made from poly (methyl methacrylate)
Preparation of potassium hydrogen sulfate in 90% sulfuric acid at 100 ° C. Immersion in a saturated solution for 30 seconds (Example 5a). The same plate was immersed in 90% hot sulfuric acid without sulfate for 30 seconds (Example 5b). Upon processing, the hydrophilic layer is substantially thicker and more uniform in the first case than in the second case, and the entire target is optically cleaner and more neutralized and water swollen. It was homogeneous.

Example 6 Added to 90% sulfuric acid before saturation with potassium bisulfate
Example 5a using 15% by weight of diethylene glycol
The procedure by was repeated. The hydrophilic swellable layer was thicker and better adhered than the plate of Example 5a.

Example 7 70% chloride prepared directly by polymerization of acrylonitrile in ZnCl ₂ solution with redox-type initiator, degassing and slow washing of zinc chloride with cold water A transparent plate made of pure polyacrylonitrile obtained from an 18% high viscosity PAN solution of aqueous zinc solution was dried at 40 ° C. and immersed in a solution of 96% sulfuric acid at 100 ° C. in warm saturated sodium hydrogen sulfate for 2 seconds. A thicker hydrophilic layer could be created by optionally removing the plate, cooling in air and repeatedly immersing briefly in an acid solution. Neutralization and washing were performed as in Example 1. A brief immersion in the salt acid solution initiated the partial crystallization of the polyacrylonitrile, thereby preventing the entire plate from heating above 70 ° C., which would result in loss of transparency.

Similar results can be obtained by immersing the plate longer in a sodium bisulfate solution heated to 60-70 ° C.

A thicker and softer water-swellable layer was formed by immersing a plate previously treated with sulfuric acid and sodium hydrogen sulfate in glycerol without prior washing.

Example 8 94% sulfuric acid saturated with potassium sulfate at 80 ° C. and glycerol
A 25% 100 ° C. warm mixture was absorbed through a bundle of hollow fibers obtained from a copolymer of 60% vinyl chloride and 40% acrylonitrile. The hollow fibers obtained after neutralization with a dilute solution of ammonia and thorough washing with water have a slightly reduced inner diameter, a hydrophilic inner surface and reduced hydrodynamic resistance (for the same inner diameter) .

Example 9 Elasticity obtained from a copolymer of ethyl acrylate and n-butyl acrylate (initial ratio of monomers 1: 1)
Example 5a and Example 5 using a 0.5 mm thick film
The procedure of b was repeated. Films treated with a saturated sodium hydrogensulfate solution in 94% sulfuric acid were uniformly hydrophilized on the surface, whereas films immersed in acid without added salt were partially hydrophilic on the surface. Dissolved and did not help at all.

The present invention is not limited to the embodiments described above, but may vary within the scope of the present invention. Therefore, the swelling of the hydrophilic layer is such that the hydrophilic layer swells most on the outside and is also softest on the outside, and furthermore the degree of hydrolysis decreases in the depth direction and thus the swelling ability decreases in the depth direction. A change in performance is conveniently achieved. This is easily achieved by separating the procedure into several steps performed under various conditions, such as time, temperature, pressure, and concentrations of the individual components. Partial or complete washing or neutralization of the reagents from the previous steps can take place between the individual steps. Of the above conditions for determining the depth of the corresponding part of the hydrophilic layer, the most important is the concentration of the auxiliary electrolyte which reduces the swelling and solubility of the polymer in hot acid. In addition to the most suitable auxiliary electrolytes, for example the readily soluble inert salts of the acids used for the hydrolysis, weaker organic acids, such as lactic acid, can also be used, but with little advantage.

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Claims (1)

(57) [Claims] 1. A core of a hydrophobic polymer containing a unit selected from the group consisting of: (a) an ester of acrylic acid, an ester of methacrylic acid, a nitrile of acrylic acid, a nitrile of methacrylic acid and a combination thereof; ) Repeat unit: Wherein R is hydrogen or methyl, and A is hydrogen, an alkali metal or a polyhydric alcohol group having two or more primary and / or secondary hydroxyl groups. A relatively thin surface layer comprising an insoluble, inert, biocompatible hydrophilic polymer; an intraocular lens or contact lens product having good optical, geometric and mechanical properties, comprising: The hydrophilic surface layer and the hydrophobic core are chemically and / or integrally bonded to form the intraocular lens or the contact lens product, and the hydrophilic surface layer is formed of acrylic acid. Manufactured from a hydrophobic polymer containing a unit selected from the group consisting of esters, esters of methacrylic acid, nitriles of acrylic acid, nitriles of methacrylic acid and combinations thereof. The target object is formed by immersing the target object in a heated strong acid containing a previously dissolved electrolyte to hydrolyze a polymer on the surface of the target object, and the electrolyte is formed by the hydrophilization. An intraocular lens or a contact lens product capable of suppressing swelling and solubility of a hydrophilic polymer in the strong acid.