CS256607B1 - Cross-linked gels on base of metacrylic acid's glycoesters with increased swelling capacity in water and method of their production - Google Patents

Abstract

Articles, such as contact lenses, made from 2-hydroxyethyl methacrylate copolymer gels, which are crosslinked with up to 2% by weight of ethylene glycol dimethacrylate, are swelled with an aqueous alkaline agent e.g. hydroxide and moderately heated until the covalent network is reorganized by interruption of the stretched cross-links and formation of new cross-links. After washing off the hydroxide with water, the swelling capacity is substantially higher than the original swelling capacity of about 40%.

Description

The invention relates to crosslinked gels of methacrylic acid glycol esters with increased swellability in water and to a process for their preparation.

Polymeric gels based on 2-hydroxyethyl methacrylate are used for the production of soft contact and intracameral lenses and various objects for medical purposes such as cosmetic fat replacements, depot shells for slow drug release, soft palate replacements, etc. These synthetic gels have proven to work well in most cases, but for some purposes their equilibrium swellability in water is 39-40% somewhat low. Therefore, numerous attempts have been made to increase the swellability of gels, for example by preparing them by copolymerizing 2-hydroxyethyl methacrylate with N-vinylpyrrolidone. This increased swelling, but at the same time tensile strength and tear resistance dropped below acceptable levels. Other highly swellable, covalently crosslinked copolymers, for example of 5-hydroxy-3-oxapentyl methacrylate, have the same disadvantage.

Insufficient strength of covalently crosslinked strong swelling gels has been found to be due to uneven crosslinking rather than high water content, and that this defect can be remedied by efficiently chemically treating finished articles or semi-products from crosslinked methacrylic acid glycol ester gels based on overstretched covalent gels. the transverse links are broken and instead new ones are formed already under increased swelling, which are not subjected to undesirable internal stress at rest, when the swollen copolymer is not subjected to external deformation forces.

The present invention provides crosslinked glycol ester gels

2S6 807 methacrylic acid with increased swelling in water, obtained by copolymerization of 2-hydroxyethyl methacrylate with 0,1 to 2% by weight, ethylenedimethacrylate, characterized in that they have a reorganized covalent network at a swelling content of 40 to 99,8% by weight ·

A process for the production of cross-linked gels based on methacrylic acid glycol esters having a degree of swelling in water at 20 DEG C. of from 40 to 99.8% by weight, with an ethylene dimethacrylate content of from 0.1 to 2% by weight of the polymerization mixture, is covalently the crosslinked gel is swollen with an alkaline solution, for example an alkaline hydroxide solution, and heated to a temperature of 20 to 5 ° C until the covalent network is reorganized with further swelling, after which the alkali is washed with water and the gel optionally stored in saline.

Alternatively, the ethylenedimethacrylate-crosslinked ethylene glycol methacrylate gel can be homogeneously swirled at 0-5 ° C with an aqueous alkaline solution, then the temperature is raised to 20-50 ° C and maintained for 2 to 48 ° C. hours. .

It has been shown that a strong alkaline caustic solution or alkaline earth metal hydroxide solution is the most suitable agent for breaking over-stretched crosslinks under strong swelling and at the same time allowing the formation of new crosslinks. The most suitable reaction temperature is about 35 ° C, close to that of the human body. Operating these agents at a slightly elevated temperature in the presence of sufficient water in the form of a reagent solution results in a reorganization of the covalent network to reduce internal stresses and concomitant higher swelling, which can be adjusted to the desired value by reagent selection and concentration, temperature and mainly duration. Partial saponification results in only a small amount of free carboxyl groups. Importantly, this treatment does not substantially reduce gel strength, although the swellability in water doubles. This can be explained precisely by the reorganization of the covalent network, in which the overstretched transverse links have been removed. The bonding tension is further reduced and the elasticity and strength of the gel is increased by transferring the swollen gel after washing the alkaline with pure water into a saline solution in which the swellability of the gel is somewhat lower than in pure water, yet

256 607

- 3 achieves high values at which, for example, the compatibility of contact lenses is increased and the wearing time without removing the lens from the eye is prolonged. · Eye tolerance is further improved by the greater softness of the gel thus treated with the same strength and deteriorated optical properties.

Gels based on methacrylic acid glycol esters crosslinked with a higher ethylene dimethacrylate content, for example instead of the usual 0.4 to 0.6% and 1 to 1.2, can also be successfully processed as described above.

Example 1

Polymerization mixture containing 35 wt. 2-hydroxyethyl methacrylate (HEMA) and 2-dimethylenedimethacrylate as crosslinking agent in a 3% aqueous solution of sodium rhodanide were polymerized for 4 hours in a glass plate form by the pyrosulfite / persulfate initiation system. The clear elastic film was removed and placed in a 3θ% sodium hydroxide container and allowed to swell at +2 ° C overnight. The foil container was then transferred to a thermostat and held at 35 ° C for 2¼ hours. The foil was then removed from the caustic and washed continuously in water at +4 ° C. After a further 24 hours, the wash was terminated. The obtained film had a swellability of 80% at 20 ° C in water and a 65% water swellability in saline at pH 7.1. The tensile and structural strength were essentially the same as for a similar gel with 40% water.

Example 2

A -5 D contact lens of 6.5 mm diameter, with a swelling of 4θ%, made in the usual manner by polymerizing 2-hydroxyethyl methacrylate with percarbonate in a rotating form was chemically treated as described in Example 1 except that heating to 35 ° C only took 18 hours. The treated lens was perfectly transparent, had a swelling capacity of 60% (at 20 ° C) in saline, a diameter of 8 mm, and a dioptric value of -5.5D. Eye tolerance was significantly better than that of a chemically untreated lens so that it could be Worn without taking off for several days without appearing veil or discomfort · The strength of the treated lens did not deteriorate despite the fact that the water content of the lens increased by 50% by weight of the polymer dry matter.

256 607

Example 3

An intracameral lens was prepared in a known manner from the xerogel obtained by copolymerizing an anhydrous mixture of 2-hydroxyethyl methacrylate with 0.8% ethylenedimethacrylate by ultraviolet irradiation after the addition of 0.2 $ benzoin. It was then swelled with water to a water content of 39%, placed in 20% potassium hydroxide and left at 0 ° C for 24 hours. Thereafter, the liquor and the lens were heated to 35 ° C for 16 hours, after which the lens was completely freed of lye in running tap water, washed with deionized water at 20 ° C and stored in 0.8% sodium chloride solution. It exhibited a swellability of $ 68.5 at 20 ° C, at tensile and structural strength approximately the same as the original water-swollen gel.

Claims (3)

Crosslinked gels based on methacrylic acid glycol esters with increased swelling in water obtained by copolymerization of 2-hydroxyethyl methacrylate with 0.1 to 2% ethylenedimethacrylate, characterized in that they have a reorganized covalent network at a water swelling content of from 40% to 99.8% by weight. 2. A process for the production of cross-linked gels based on methacrylic acid glycol esters having a degree of swelling in water at 20 DEG C. of from 40% to 99.8% by weight, with an ethylene dimethacrylate content of from 0.1 to 2% by weight, of a polymerization mixture. The covalently crosslinked glycol methacrylate gel is treated with an alkaline solution such as an alkali hydroxide and heated to 20 to 50 ° C until the covalent network is reorganized with further swelling, whereupon the alkali is washed with water and the gel is optionally stored in saline. 3. A process according to claim 2, wherein the ethylenedimethacrylate-crosslinked ethylene glycol methacrylate gel is first allowed to swirl homogeneously at 0-5 [deg.] C. with an aqueous alkaline solution such as an alkali hydroxide, while maintaining the temperature at 20-50 [deg.] C. 2 to 48 hours.