DE102006004111B4 - Contact lens material - Google Patents

Abstract

A contact lens material having an alkyl ammonium halide derivative copolymerized in a HEMA or sulfobetaine base material as a comonomer, characterized in that by polymerizing an alkyl ammonium derivative having the structural formula, or wherein R is a methyl or ethyl group, or by copolymerizing N-methacryloyl amidopropyl N- ( 4-trimethoxysilethyl) -benzyl-N, N-dimethyl-ammonium chloride (AMSi) has a hydrated content of 50-70% by weight.

Description

The invention relates to a contact lens material according to the preamble of the main claim. Contact lens materials should preferably have a high water content, good oxygen permeability, a good water retention behavior, a good sliding surface, good optical properties, good processing properties and good mechanical properties, such as tear resistance. The contact lens materials should also have approximately the properties of the cornea of the human eye.

The water content of the cornea is usually about 65 to 75 wt .-%, which is due to an extremely high water retention capacity of the cornea itself. This retention of water prevents an excessive decrease in surface moisture in dry air, such as in cold (polar) air, as well as in air-conditioned spaces with high water evaporation, such as in airplanes. At the same time, the high water retention capacity simultaneously prevents the concentration of the substances dissolved in the tear fluid from increasing too much in the event of otherwise high evaporation and then crystallizing out.

In this context it is known that sulfo compounds, in particular keratan sulfates and chondroitin sulfates, play a role in the water retention capacity of the natural cornea.

In addition to the special property of the water retention capacity, the cornea must also have a high oxygen permeability, because the cornea has on its inside an endothelial cell layer, the oxygen supply is not through vessels, but from the ambient air through the cornea. However, a constant exposure of the cornea to the ambient air would result in its drying out despite its high water retention capacity. To avoid this, the cornea is therefore permanently affected by blinking with a liquid called tears, which contains dissolved proteins, lipoproteins, lipids and mucins.

Due to the constant re-supply of this liquid and its evaporation on the ocular surface, these substances dissolved in the tear fluid would have to deposit on the cornea and cloud them. In order for this not to happen, nature has developed protective mechanisms that have not yet been fully elucidated.

However, it is known that in nature the deposition of the above-mentioned substances on the corneal surface is also avoided by a betaine structure within the collagen. The collagen of the cornea contains as amino acids glycine, proline, glutamine, alanine, arginine, asparagine, lysine, leucine, serine, isoleucine and others.

When making contact lenses, it is therefore necessary to ensure that the physiological tasks of the cornea are essentially not impaired by the contact lens placed on the cornea and thus by covering a portion of the cornea. This can be achieved by having the contact lens approximately the same properties as the cornea of the eye, wherein care must also be taken that the refractive index of the contact lens should be close to the refractive index of the cornea of 1.37.

From the US 5,311,223 A a hydrogel contact lens is known whose polymer composition consists of a reaction product of a hydrophilic methacrylamide and an acrylic monomer, which in a preferred embodiment, a zwitterionic monomer such. As a sulfobetaine, z. B. N- (3-sulfopropyl) -N-methacryloxyethyl-N, N-dimethylammonium betaine (SPE) to improve the water retention capacity. In addition, it is from the US 4,663,409 A It is known to improve the water retention capacity by incorporating amino acid monomers into the matrix of a hydrogel contact lens. However, the water retention was still unsatisfactory in many cases.

Contact lens material for Hydrogelkontaktlinsen is for example from the US 4,463,149 A and the US 4,472,327 A Known, wherein care agents for Hydrogelkontaktlinsen example in the EP 0 076 136 B1 and in the US 2005/0080245 A1 are disclosed.

The object of the invention is therefore to provide a material for contact lenses, in particular for one-day contact lenses and up to one month worn hydrogel contact lenses, which has an advantageous combination of said properties. A production in the casting method is desired in a preferred embodiment.

To achieve the object, a material with the features of claim 1 is proposed according to the invention, that also can be cleaned in contact lens mold with a care agent that contains the same material as a water-soluble solution polymer.

In essence, the invention is that in the base material of a contact lens material at least one Alkylammoniumhalogenid derivative is copolymerized as a comonomer.

oder ein Alkylammoniumamidhalogenid der allgemeinen Formel

handeln, wobei R1: verzweigter oder unverzweigter, bevorzugt C2, Alken-Rest,
R2: verzweigter oder unverzweigter, bevorzugt C2-C3, Alkylen-Rest,
R3: verzweigter oder unverzweigter, bevorzugt C1-C12, Alkyl-Rest,
m: verzweigter oder unverzweigter, bevorzugt C1-C20, Alkylen-Rest,
R4: verzweigter oder unverzweigter, bevorzugt C1-C20, Alkoxycarbo- oder Phenyl- oder Alkoxysilyl-Rest
R5: Halogen
bedeutet.In this case, the alkylammonium halide derivative may be an alkylammonium ester halide of the general formula

or an alkylammonium amide halide of the general formula

where R1: branched or unbranched, preferably C2, alkene radical,
R 2: branched or unbranched, preferably C 2 -C 3, alkylene radical,
R 3: branched or unbranched, preferably C 1 -C 12, alkyl radical,
m: branched or unbranched, preferably C 1 -C 20, alkylene radical,
R 4: branched or unbranched, preferably C 1 -C 20, alkoxycarbo or phenyl or alkoxysilyl radical
R5: halogen
means.

The comonomer is preferably an alkylammonium chloride derivative, although other halides, for example bromides or iodides, are also conceivable. The alkylammonium chloride derivative is preferably N-carbomethoxymethyl-N-methacryloylamidopropyl-N, N-dimethylammonium chloride (AM1M) or N-carboxyethoxymethyl-N-methacryloylamidopropyl-N, N-dimethylammonium chloride (AM1E) or any of those described in the table below 1 listed alkylammonium halide derivatives.

The base material preferably consists of hydroxyethyl methacrylate (HEMA) and / or hydroxypropyl methacrylate (HPMA) and / or a sulfobetaine, more preferably N, N-dimethyl-N- (2-methacryloyloxyethyl-N- (3-sulfopropyl) ammonium betaine (SPE) , or a mixture thereof.

Preferably, the contact lens material according to the invention is produced by heat polymerization or by polymerization with UV light. The hydrogel contact lenses made of this material are furthermore preferably produced by a cutting process from a bar material or directly by casting.

Finally, a care agent for the hydrogel contact lens according to the invention is provided which contains the polymer according to the invention prepared under conditions of solution polymerization as a solution polymer.

The invention is explained in more detail below with reference to examples:
Starting from a base material commonly used for producing contact lenses, for example, hydroxyethyl methacrylate (HEMA) or N, N-dimethyl-N- (2-methacryloyloxyethyl-N- (3-sulfopropyl) ammonium betaine (SPE), a comonomer was sought which polymerized Contact lens material gives the necessary for further processing to the contact lens properties mentioned above.

Surprisingly, it has been found that choline chloride is suitable as a starting material for the production of hydrogel material. Choline chloride is a hygroscopic substance which is present in crystalline form as a white powder and in water and in polar organic solvents, such. As methanol, ethanol, dimethylformamide, is soluble. Choline chloride is also known in the physiology as vitamin B4 and is mainly called Feed additive used, for example for pig fattening. For humans, a daily intake recommendation is not fixed, since it is usually supplied with sufficient food.

Due to its physiological harmlessness, its good solubility in water and its hygroscopic property, choline chloride has good conditions for use in contact lenses in comparison with the known toxic, liquid monomers, such as, for example, N-vinyl-2-pyrrolidinone or N, N-dimethylacrylamide.

However, the problem initially appeared to be that a vinylogous double bond must be introduced into the choline molecule without substantially altering its structure in order to produce a polymer suitable as a contact lens material. In particular, the ammonium structure must be retained to maintain the interaction between the polymer and water.

In principle, this was specifically on in the US 2,777,872 A and US 2,744,130 A recited methods for the preparation of Cholinesterchloriden recourse. In this case, tertiary amines are reacted with chloromethylacetic esters, benzyl chloride or bromomethylbenzophenone in acetonic solution at room temperature. The methacrylate or acrylate group can be introduced as ester or amide:

It was found that the alkyl ammonium chlorides thus prepared are very soluble in HEMA and can be processed by the known methods to cast molded contact lenses and rods. It has also proved advantageous in this method that the starting materials are relatively cheap and the yield of the reaction product is very good.

The polymerization was carried out using the alkylammonium chlorides already mentioned in Table 1, which were synthesized from the starting materials indicated in the table A and B according to the instructions exemplified below for the alkylammonium chloride AM1M.

The alkylammonium chloride AM1M is prepared from the starting material A: methacrylic acid (3-dimethylaminopropylamide) and the starting material B: chloroacetic acid methyl ester. For this purpose, 17.03 g (corresponding to 0.1 mol) of methacrylic acid (3-dimethylaminopropylamide) [MW 170.25] are dissolved in 40 ml of acetone and treated with a solution of 11.94 g (corresponding to 0.11 mol) of methyl chloroacetate [MW 108.52] in 20 ml of acetone with vigorous stirring at room temperature. The overnight precipitated crystals are washed three times with acetone p. A. and dried in vacuo at 30 ° C. The resulting product AM1M (N-carbomethoxymethyl-N-methacryloylamidopropyl-N, N-dimethylammonium chloride) is stored in the desiccator over calcium chloride until further processing.

All alkylammonium chlorides could be prepared with a yield greater than 90% of the theoretical value. All alkylammonium chlorides are solid (crystalline) substances which could be polymerized uncritically in the heat when dissolved in known liquid monomers.

For the preparation of the contact lens material, in addition to an alkylammonium halide, for example, one or more of 2-hydroxyethymethacrylate (HEMA), ethylene glycol dimethacrylate (EGA), 2- (2'-hydroxy-5'-methacryloyloxyethylphenyl) -2H-benzotriazole (UVA), isobornyl methacrylate (IBMA ), 2,2'-azobis (2,4-dimethylvaleronitrile) (V-65), 2,2'-azobis (2-methylbutyronitrile) (V59) and poly (ethylene glycol) methacrylate (polyglycol) MA) taken from the corresponding production approaches and either processed into bar stock or directly to contact lenses. For example, a production batch was 83.7 weight percent HEMA, 15 weight percent AM2E, 0.4 weight percent EGA, 0.5 weight percent UVA, and 0.4 weight percent V65.

Polypropylene (PP natural, 16 × 13 mm, 235 mm, Gehr) tubes were loaded with 16 g per tube to produce rod material. After filling, the tubes were sparged with nitrogen for 10 minutes and then the polymerization was carried out with the following temperature / time. Program carried out: 45 ° C / 24 h; 60 ° C / 24 h; 90 ° C / 24 h. After demolding, the rods were annealed at 90 ° C / 24 h.

For the direct production of contact lenses, the reaction mixture was filled in polypropylene molds and molded the contact lens for one hour at 100 ° C. However, the polymerization can also be carried out with UV light (λ = 300-400 nm, 3-6 mW / cm ² , for 3 hours at room temperature) for example with Darocur 1173 (Ciba-Geigy Corp.) as photoinitiator. The amount of monomer averaged 70 μl per mold. The swelling was carried out in physiological saline under sterilization conditions (121 ° C for 20 min).

The contact lens material according to the invention has the structure shown by way of example below for AM1E:

The contact lens material is physiologically non-toxic as a polymer. The extraction of unpolymerized residual monomers from the contact lens material is easy, since the monomers used are fully water-soluble.

Poly(ethylacrylat-co-methylmethacrylat-co-2-trimethylammonioethyl)methacrylatchlorid Preferably, further monomers or else copolymers can be copolymerized into the base material. These are on the one hand UV-absorbing substances. Inventive contact lenses, which are equipped, for example, with 0.5 wt .-% UV absorber, a light transmission of 2% UVB, 8% UVA and 98% visible light. On the other hand, it is possible to polymerize substances having a bactericidal and / or fungicidal action. For example, an excipient (MetoHEXAL / Hexal) already used in the manufacture of medicaments could be used as copolymer, which is prepared, inter alia, from N-methacryloyloxyethyl-N, N, N-trimethylammonium chloride.

methacrylate chloride poly (ethyl acrylate-co-methyl methacrylate-co-2-trimethylammonioethyl)

As a further example, the bactericidal and fungicidal action could also result from the copolymerized AMB, the monomer structure of which is similar to the benzalkonium chloride already used in care products as a bactericide:

The advantage of bactericidal and / or fungicidal functional groups polymerized in the contact lens material is that the likelihood of fouling of the contact lens according to the invention with (pathogenic) organisms is reduced permanently and from the beginning. This also means that the contact lenses no longer need to be intensively cleaned with cleaning solutions, which often remain in the contact lens matrix and lead to irritation of the eye when the contact lens is worn.

The hydrogel contact lens according to the invention made of the contact lens material according to the invention has in hydrated form a water content of more than 50% by weight, preferably between 54 and 70% by weight, with improved water retention behavior compared to known hydrogel contact lenses. It is also particularly advantageous that the surface of the contact lenses feels soapy and thus contributes to a pleasant wearing feeling. At the same time, the contact lens is extremely tear-resistant and heat-sterilizable.

A particular advantage of the contact lens material according to the invention is that in contrast to the known anionic contact lens materials, they are cationic polymers. Namely, in the physiological pH range, the halide ion can not be split off and replaced by other anions (eg, acidic proteins). But this keeps the properties of the contact lens constant. Thus, for example, a change in the swelling or an increased adsorption capacity of the contact lens material for proteins could only be achieved by treatment with a 2N sodium hydroxide solution (pH> 12) since it is only at this pH that the OH ^- form of the alkylammonium halide, the salt of a weak base and a strong acid is obtained.

The contact lens material according to the invention can also be used as silicone hydrogel (see Table 1: AMSi). For this purpose, the substitution of an alkyl group of the ammonium salt (ammonium chloride, iodide, bromide, etc.) by a silicon-containing organic compound, for. B. trimethoxysilane (m, p-chloromethyl) -phenylethane, necessary. With such a substance, a "multifunctional monomer" is obtained, with which both the water content, which is determined by the ammonium function, and the oxygen permeability (Dk value), which is controlled by the silicon content of the polymer.

In addition, the use of silicon-containing ammonium salts is advantageous for adjusting the hydrophilic surface of RGP (Rigid Gas Permeable) contact lenses. In contrast to the currently used methacrylic acid, the hydrophilic monomer according to the invention contains silicon and thereby increases, in addition to the hydrophilicity, the Dk value of the material.

Finally, the polymers of the invention can also be prepared under conditions of solution polymerization as water-soluble substances and offered in the form of a contact lens care product. The contact lenses would be coated with a lubricious layer during care and, at the same time, preferably germ-free by a macromolecular disinfectant that can not penetrate the contact lens matrix.

Claims (5)

A contact lens material having an alkyl ammonium halide derivative polymerized into a HEMA or sulfobetaine base material as a comonomer, characterized in that by copolymerizing an alkyl ammonium derivative having the structural formula

or

wherein R is a methyl or ethyl group, or by copolymerizing N-methacryloylamidopropyl-N- (4-trimethoxysilethyl) -benzyl-N, N-dimethyl-ammonium chloride (AMSi)

a water content in hydrated form of 50-70 wt .-% is present. Contact lens material according to claim 1, characterized in that the base material

N, N-dimethyl-N- (2-methacryloyloxyethyl-N- (3-sulfopropyl) ammonium betaine. Contact lens material according to one of the preceding claims, characterized in that, to adjust the oxygen permeability, an alkyl group of the ammonium chloride is substituted by a silicon-containing organic compound. Contact lens material according to one of the preceding claims, characterized in that there is an admixture of silicon-containing ammonium salts to adjust the hydrophilicity. Contact lens material according to one of the preceding claims, characterized in that

N-Benzyl-N-methacryloylamidopropyl-N, N-dimethylammonium chloride is copolymerized into the base material.