WO2008055482A1 - Contact lens material - Google Patents

Abstract

Disclosed is a contact lens material which comprises a hydrophilic comonomer and a hydrophobic comonomer and is characterized in that a free methacryloyl amino acid is polymerized into the contact lens material.

Description

 Contact lens material

The invention relates to a contact lens material, in particular for producing a silicone hydrogel contact lens.

Due to advancing technological developments in materials science and process engineering, which lead to high-quality products that are also reproducible in their special parameters, contact lenses (also called adhesive shells) are gaining in importance over spectacles. Most refractive errors, such as myopia, farsightedness and presbyopia and astigmatism, can usually be corrected very well with the help of contact lenses, often even better than with conventional glasses.

In principle, there are two types of contact lenses: hard contact lenses and soft contact lenses. While the hard contact lenses, which are originally made of glass, but now made of anhydrous polymers, such as polymethyl methacrylate (PMMA), are dimensionally stable, the soft contact lenses, which are made of hydrogels referred to organic polymers, such as polyhydroxyethyl methacrylate, flexible and adapt to the surface of the cornea.

Which type of contact lens is preferred by a contact lens wearer is above all dependent on the living circumstances of the respective person. Compared with soft contact lenses modern rigid hard contact lenses have the advantage of a two to seven times higher gas permeability, which provides the cornea can be better supplied with oxygen and therefore in principle a higher continuous gestation time is reached. Therefore, it has already been attempted to develop a contact lens material for soft contact lenses, which allows a longer wearing time, so that the soft contact lenses, e.g. can also be kept overnight on the eye.

Since the cornea is supplied with oxygen mainly by direct contact with the air, but the cornea is covered by the contact lens in a large partial area, is the for a longer wearing time of a contact lens critical parameters the oxygen permeability of the contact lens. To increase this, several approaches are known:

By reducing the thickness of the contact lens, an attempt is made to reduce the diffusion distance of the oxygen from the air to the squamous epithelium of the cornea. Disadvantage of this procedure, however, is that very thin contact lenses are difficult to handle and a reduction in the center thickness of the contact lens are set below 50 microns limits.

- As an alternative or additional measure, it is also known, the water content of

Increase contact lens. However, contact lenses with a high water content are extremely soft and thus again difficult to handle. A better handling would be possible only with thicker contact lenses, which, however, again reduce the oxygen permeability and counteract the effect achieved by the incorporation of water.

The use of other materials with high oxygen permeability values, for example silicones, has the disadvantage that their surfaces are hydrophobic and therefore can not be wetted by the tear fluid. They tend to attach themselves to the eye and are therefore not very well suited as a contact lens.

On the basis of these observations, it has been attempted to combine the properties of the silicones, which are advantageous in terms of oxygen permeability, with the properties of the hydrogels which are advantageous with respect to the water content. After initial attempts in which either lost the desired properties of the monomers in the copolymer or opaque materials emerged from it, it is now possible to produce certain silicone hydrogels, which are transparent and have both a favorable water content and a good Oxygenermermeabilität.

However, a disadvantage of these known silicone hydrogel contact lens materials is that they nevertheless - although they absorb a lot of water - are water-repellent on their surfaces and not (with tear liquid) wettable. In order to make these also compatible for use as a contact lens, various methods for surface treatment of the contact lens are necessary, for example, plasma modification, which, although the desired Er- but are very costly and time-consuming and require a high degree of know-how as well as material and personnel deployment.

The object of the invention is therefore to provide a contact lens material which has an advantageous water absorption capacity and at the same time an advantageous oxygen permeability, wherein an additional surface treatment, for example by plasma modification, can be dispensed with.

The object is achieved by a contact lens material with the features of claim 1. The subclaims give advantageous embodiments of the invention again.

The invention is based on the knowledge of the inventors that the use of a methacryloyl-amino acid as a comonomer of a known reaction mixture of a hydrophilic monomer, for example 2-hydroxyethyl methacrylate (2-HEMA), and a hydrophobic monomer, for example siloxane compounds, in one Copolymer results that has an average water content of preferably between 30 and 50% and an oxygen permeability (ie a Dk value) of 60 to 120 barrers and at the same time a hydrophilic, wettable surface, so that additional surface treatments can be omitted after polymerization.

The hydrophilic comonomer is preferably one of the compounds:

N, N-dimethylacrylamide N-vinylpyrrolidinone-2 2-hydroxyethyl methacrylate

or a copolymer consisting of these monomers and the hydrophobic comonomer is preferably one of the compounds

3-Methacryloyloxypropyl tris (trimethylsiloxy) silane or the PDMS derivatives of the formulas

or a copolymer consisting of these monomers.

The methacryloyl amino acid is preferably one of the following compounds: NH ₂ CH ₂ CH ₂ CH ₂

CH ₃ CH ₃ CH ₂

CH ₂ = C-CO-NH-CH ₂ -COOH CH ₂ = C-CO-NH-CH-COOH

N-methacryloyl-glycine N-methacryloyl-lysine

or

N-Methacryloyl-Prolin,

N-methacryloyl-proline,

wherein not only a methacryloyl amino acid can be used in a contact lens material, but two or more of these amino acids.

The invention will be explained in more detail below with reference to examples.

example 1

To prepare a uniform material mixture that can be used to produce high quality silicone hydrogel contact lenses, two solutions, namely a hydrophilic and a hydrophobic solution, are prepared in parallel in suitable stirred glass vessels. The following rule is based on Approach 1 of the attached Table 1.

Hydrophilic solution: 10 parts by weight of distilled 2-hydroxyethyl methacrylate (2-HEMA) are premixed and dissolved at room temperature (RT) with high purity methacryloyl-glycine (MA-Gly, 0.5 part by weight). Then 20 parts by weight of distilled N, N-dimethylacrylamide (N ₅ N-DMA) and 12 parts by weight of distilled N-vinylpyrrolidone (N-VP) are added and the mixture is stirred for about 1 h. Hydrophobic solution:

In a stirred vessel, the siloxane compounds are mixed and stirred in any order. Advantageously, the distilled 3-methacryloyloxypropyl-tris (trimethylsiloxy) silane (TRIS) is initially charged and the macromers added (12 parts by weight of polydimethylsiloxane, bis-methacrylate 1000 (bMA-PDMS 1000) and 5 parts by weight of polydimethylsiloxane, mono-methacrylate 1000 (mMA-PDMS 1000)).

The two above-mentioned homogeneous, colorless solutions are combined with the addition of 12 parts by weight of 3-methyl-3-pentanol and 6 parts by weight of nonanol and stirred thoroughly. A few minutes later, components V-65 (1.0 part by weight), TEGDMA (0.3 part by weight) and EGDMA (0.7 part by weight) are added and dissolved by stirring at room temperature. After 45 minutes, the mixture is homogenized for nitrogen gassing (about 5 minutes) and then prepared for bottling.

Example 2

As in Example 1, different material mixtures were produced to thereby obtain different contact lens properties. Depending on the composition of the hydrophilic and the hydrophobic solution, as shown in Table 1 below, the Dk value (ie the oxygen permeability) of the resulting polymer and the water content, as well as indirect properties such as, for example, surface wettability, elasticity, friction coefficient ("lubricity"), etc. are varied.

Production of Silicone Hydrogel Contact Lenses (SiHy Contact Lenses)

A) casting lenses

The SiHy contact lenses are produced using the prepared, degassed monomer / macromer mixture from Examples 1 to 10.

These reactive mixtures are filled by means of a suitable dosing technique in the prepared concave mold halves, which are used for direct lens imaging. Depending on the desired lens diameters and diopters, the dosing volumes are in the range of 55 to 75 μl for a contact lens. The filling should take place under suction in a low-dust area. Shortly after filling, the associated upper mold shell (convex shape) is placed by a uniform and quiet settling movement and the one mold halves stabilized in position. The polymerization to the contact lens can be carried out by high-energy irradiation or by heat, or preferably by a combination of both energies.

If it is intended to polymerize only by supplying heat, a process time of 1 to 5 hours is required in order to achieve a sufficiently complete polymerization. Process times of 3 hours at a process temperature in a circulating air oven of about 110 to 120 ^° C. are preferred. At lower temperatures, correspondingly somewhat longer process times are required. As is known, it is also possible to influence the process time and temperature via the amount of initiator.

A widely practicable method of polymerizing thin layers is the combination of heat and light energy. For this purpose, the contact lens mixture is mixed with heat-sensitive and light-sensitive initiators. The use of highly reactive heat initiators using the aforementioned energy combination is less effective, but good conversion can nevertheless be achieved.

Common, commercially available photoinitiators can be used in the usual proportions of preferably 0.1 to 1.0 parts by weight. Good reactivity with UV-A light show, inter alia, the commercial products Darocur ^® (Ciba), and Lucirin ^® (BASF). This combination of highly reactive photoinitiators and heat initiators in the contact lens mixture can significantly shorten or reduce the process time and process temperature. This results in economic and qualitative advantages:

At process times from a few minutes to 1 hour, the throughput can be increased and, in the event of an after-reaction with e.g. 70 to 100 ° C, preferably 80 to 95 ° C, the risk of plastic deformation of the lens mold can be reduced. The preferred plastic for the molds is polypropylene (PP) and thus a material whose heat resistance significantly decreases above 100 ° C.

The post-curing of the UV-polymerized lenses can usually take place within 5 to 45 minutes, preferably in 15 to 30 minutes. B) Blank rod material for silicone hydrogel contact lenses

The SiHy contact lenses are produced using the prepared, degassed monomer / macromer mixture from Examples 1 to 10 (Table 1).

The production of blank or rod material requires a filling of the said mixtures into suitable tubes whose material is preferably plastic, in particular polypropylene (PP). The material polymerization is also possible in other materials such as glass or metal, but often associated with higher workload and process costs. The tubes are therefore usually made of polyethylene (PE) or polypropylene (PP) preferred and introduced after the filling and a further fumigation and evacuation in thermal baths or ovens for thermal polymerization. The sealed tubes or blank molds are then polymerized in a multistage thermal process adapted to the blends.

For rod polymers of approx. 5 to 15ml starting material, the following process has proved successful:

Process example: 70 h at 30 ⁰ C, then at 45 ° C for 20 h, then at 60 ° C for 26 h, then at 80 ° C for 24 h and finally at 90 ° C for 24 h; Cooling passively (about 30 h)

The mechanically demolded bars or blanks are then tempered in a subsequent process. In a vacuum oven, the expanded polymers are heated to about 60 ° C and evacuated after 24 h. The mixture is then re-aerated and isothermally annealed at 60 ° C for 72 h.

For this example, there are numerous variants that influence the molecular shape of the resulting lens eigenscales by shortening or lengthening individual process stages. Furthermore, the external factors, such as the wall thicknesses of the tubes, the type of heat source, the amount of residual oxygen in the material mixture, etc., are specific quantities that must be taken into account in the process definition.

The blank / rod polymers are then used under conditioned conditions in a suitable processing method for individual contact lenses. The resulting contact lenses must first be extracted similar to the cast lenses before being rinsed in physiological saline and then autoclaved / sterilized for storage or shipment in buffered saline.

The contact lenses produced by way of example with reference to Table 1 are characterized by an acceptable to good tear strength, good lubricity and good transparency. In addition to the above-mentioned properties with respect to the water content, preferably between 30 and 50% and a Dk value between 60 and 120 barrers, the contact lenses thus produced also exhibit good water-binding properties, which correspond to a contact lens prepared according to approach 7 of Table 1 in comparison with other hydrogels - Contact lenses and silicone Hydrogelkontaktlinsen in the single Fig. 1 are shown.

Fig. 1 shows dehydration measurement curves of various contact lenses under standardized conditions. The contact lens to be examined was stored over a period of about 20 minutes in a climate chamber over silica gel at 22 ° C and a relative humidity of 15%, with their water loss was measured. Compared with the known hydrogel contact lenses and also the known silicone hydrogel contact lenses, the contact lens according to approach 7 of Table 1 shows an improved water-binding capacity.

Contact lenses made of a contact material with a proportion of methacryloyl amino acids of at least 0.2% by weight, preferably at least 0.8% by weight, have proved to be particularly advantageous. The content of DMA is preferably between 16 and 26% by weight, the content of N-VP preferably between 9 and 12% by weight and the content of 2-HEMA preferably between 4 and 8% by weight. TRIS preferably has a proportion of between 30 and 40% by weight, the proportion of bMA-PDMS 1000 preferably being approximately 10% by weight.

Table 1

Abkürzungen:

Abbreviations:

2-HEMA 2-hydroxyethyl methacrylate

AMA allyl methacrylate b A-PDMS 1000 polydimethylsiloxane, bis-acrylate 1000 bMA-PDMS 1000 polydimethylsiloxane, bis-methacrylate 1000 bMA-PDMS 3000 polydimethylsiloxane JBis methacrylate 3000

BTMAEPh 2- (2-hydroxy-5-methacryloxyethylphenyl) -2H-benzotriazole

Darocur 1173 2-hydroxy-2-methyl-1-phenylpropane-1-one

EGDMA ethylene glycol dimethacrylate

MA-Gly methacryloyl-glycine

MA-Lys methacryloyl-lysine

MA-Pro methacryloyl-proline niMA-PDMS 1000 polydimethylsiloxane, mono-methacrylate 1000mM-PDMS 4500 polydimethylsiloxane, mono-methacrylate 4500

N ₅ N-DMA N, N-dimethylacrylamide

N-VP N-vinylpyrrolidone

RT room temperature

TEGDMA tetraethylene glycol dimethacrylate

TPO 2,4,6-trimethylbenzoyldiphenyl-phosphine oxide

TRIS 3-methacryloyloxypropyltris (trimethylsiloxy) silane

V-65 2,2'-azodi- (2,4-dimethylvaleronitrile)

Claims

W 5197 A contact lens material comprising a hydrophilic comonomer and a hydrophobic siloxane comonomer, characterized in that in the contact lens material, a free methacryloyl amino acid is copolymerized. 2. Contact lens material according to claim 1, characterized in that the hydrophilic comonomer is selected from the group of

N, N-dimethyl acrylamide,

N-vinyl-pyrrolidinone 2 and

2-Hydroxyehthylmethacrylat. 3. Contact lens material according to one of the preceding claims, characterized in that the hydrophobic siloxane comonomer

3-methacryloyloxypropyl tris (trimethylsiloxy) silane and and at least one of the PDMS derivatives selected from the group of

Contact lens material according to one of the preceding claims, characterized in that the methacryloyl amino acid is selected from the group of CH ₃ CH ₂ = C-CO-NH-CH ₂ -COOH N-methacryloyl-glycine,

N-methacryloyl-lysine and

N-methacryloyl-proline. 5. Contact lens material according to one of the preceding claims, characterized in that the contact lens material has a Dk value between 60 and 120 barrer and a water content between 30 and 50%. 6. Contact lens, characterized in that the contact lens comprises a contact lens material according to one of claims 1 to 5.