JP4701952B2 - Hydrous soft contact lens - Google Patents

Description

  The present invention relates to a hydrous soft contact lens having high water content and excellent transparency and flexibility.

  The hydrous soft contact lens (hereinafter abbreviated as SCL) mainly composed of a hydrophilic monomer is compared with a non-hydrous hard contact lens composed mainly of a hydrophobic monomer such as methyl methacrylate and siloxanyl alkyl methacrylate. It has the characteristics of being familiar to the eyes and excellent in wearing feeling. As this hydrophilic monomer, for example, a polymer mainly composed of 2-hydroxyethyl methacrylate has been known for a long time. However, although it has excellent heat resistance, mechanical strength and stability, it has a low water content, so that it can transmit oxygen. The rate (Dk value) was low, and the wearing feeling was not satisfactory as SCL.

For this reason, a polymer obtained by copolymerizing a more hydrophilic monomer such as N-vinylpyrrolidone, methacrylic acid or N, N-dimethylacrylamide has been proposed in order to increase the water content. However, all of them have problems in that the mechanical strength as SCL decreases, deterioration due to repeated heat treatment, and dirt due to tears easily adhere to the lens.
Therefore, recently, soft contact lenses having higher hydrophilicity than 2-hydroxyethyl methacrylate are proposed in Patent Documents 1 to 3, and Patent Document 4 as a monomer proposes a material using glyceryl methacrylate. However, these existing monomers can provide SCL with improved moisture content, but have problems such as flexibility and easy breakage.
JP-A-10-177152 JP 2000-111847 A JP 2001-142034 A JP 58-009121 A

  An object of the present invention is to provide a water-containing soft contact lens having high water content and excellent in transparency, flexibility and antifouling property.

(式中、Ｒ₁は水素原子又はメチル基、Ｒ₂は−(CH₂)n−で示される基、Ｒ₃は−(CH₂)m−で示される基を示す。ここで、ｎは１〜４、ｍは１〜８の整数である。AOは炭素数２〜４のオキシアルキレン基、ｘは０〜１０００の整数である。) As a result of diligent studies to solve the above problems, the present inventors have found that a urethane bond-containing diol having both a hydrophilic (meth) acrylate group and a hydrophilic urethane bond in the molecular structure and a plurality of hydroxy groups. The present inventors have found that a polymer containing a (meth) acrylate compound solves the above problems, and has completed the present invention.
That is, according to the present invention, a hydrous solution containing a polymer obtained by polymerizing a raw material monomer containing a urethane bond-containing diol (meth) acrylate compound represented by formula (1) (hereinafter referred to as compound (1)). A soft contact lens (hereinafter abbreviated as SCL) is provided.

(Wherein R ₁ represents a hydrogen atom or a methyl group, R ₂ represents a group represented by — (CH ₂ ) n —, and R ₃ represents a group represented by — (CH ₂ ) m —, where n is 1-4 and m are integers of 1 to 8. AO is an oxyalkylene group having 2 to 4 carbon atoms, and x is an integer of 0 to 1000.)

  Since the SCL of the present invention contains a polymer obtained by polymerizing a raw material monomer containing the compound (1) having both a hydrophilic urethane bond and a hydroxy group in the molecular structure of the (meth) acrylate compound, it is sufficient for the cornea of the eye. Oxygen can be supplied, and since it has excellent flexibility and elongation at break, it feels good to wear and handle. It also has antifouling properties.

Hereinafter, the present invention will be described in more detail.
The compound (1) used in the present invention is a urethane bond-containing diol (meth) acrylate compound represented by the formula (1). In the formula, R ₁ represents a hydrogen atom or a methyl group, and a hydrogen atom is preferable from the viewpoint of high photopolymerization. R ₂ represents — (CH ₂ ) n —, and n is an integer of 1 to 4. R ₂ is specifically _{-CH 2 -, - CH 2 CH} 2 -, - CH 2 CH 2 CH 2 -, - CH 2 CH 2 CH 2 CH 2 - are either, from easy availability - CH ₂ CH ₂ — is preferred. R ₃ represents — (CH ₂ ) m —, and m is an integer of 1 to 8. The R _3, for _{example, -CH 2 -, - CH 2} CH 2 -, - CH 2 CH 2 CH 2 -, - CH 2 CH 2 CH 2 CH 2 - and the like, from easy availability - CH ₂ - is preferred. (AO) _X in (AO) represents an oxyalkylene group having 2 to 4 carbon atoms, and x is an integer of 0 to 1000. x is not 0 (AO) _X is, for example, a polymer residue consisting of an oxyethylene group, an oxypropylene group, and an oxybutylene group, and x is an oxyethylene group of 0 to 500 for ease of synthesis. Or it is preferable that it is the polymer residue.

  Examples of the compound (1) include glyceryl-1-methacryloyloxyethyl urethane, 3,4-dihydroxybutyl-1-methacryloyloxyethyl urethane, 5,6-dihydroxyhexyl-1-methacryloyloxyethyl urethane, glycerin (- Monopolyethyleneglycol-1-methacryloyloxyethylurethane, glycerin (-monopolypropyleneglycol-1-methacryloyloxyethylurethane and the like can be mentioned, and glyceryl-1-methacryloyloxyethylurethane is preferred for ease of synthesis.

In order to prepare the compound (1) used in the present invention, for example, a cyclic ketal and (meth) acryloyloxyalkyl isocyanate are urethanated and then hydrolyzed in a water-containing solvent in the presence of a catalyst. It can be obtained by a ring reaction method or the like.
Examples of the cyclic ketal include 2,3-o-isopropylideneglycerol, 3,4-o-isopropylidenebutanol, 5,6-o-isopropylidenehexanol, 2,3-o-sec-butylideneglycerol, 3,4-o-sec-butylidenebutanol, 5,6-o-sec-butylidenehexanol, 2,3-o-isopropylideneglycerol (-monopolyethylene glycol, 2,3-o-isopropylideneglycerol (- Monopolypropylene glycol and the like can be mentioned, and 2,3-o-isopropylideneglycerol is preferred from the viewpoint of easy reaction.

  Examples of the (meth) acryloyloxyalkyl isocyanate include methacryloyloxyethyl isocyanate, methacryloyloxypropyl isocyanate, etc., and methacryloyloxyethyl isocyanate is preferred from the viewpoint of availability. As such isocyanate, a commercially available product may be used, or a product synthesized from a known raw material by using a known synthesis method may be used.

As another method for preparing the compound (1) used in the present invention, for example, the (meth) acryloyloxyalkyl isocyanate and glycerin, glycerin (-monopolyethylene glycol or glycerin (-monopolypropylene glycol) are urethanated. The method of making it also includes.
The urethanization reaction proceeds without using a catalyst, but since the reaction time can be shortened, the reaction temperature is 0 to 100 ° C. and the reaction time is about 6 to 24 hours using a catalyst for urethanization reaction. be able to.

The polymer used in the present invention is a polymer obtained by polymerizing a raw material monomer containing the compound (1), and the molecular weight of the polymer is usually 5000 or more in terms of weight average molecular weight.
In the raw material monomer, the content ratio of the compound (1) is usually 5 to 100% by mass, preferably 10 to 95% by mass. If it is less than 5% by mass, the desired effect may not be obtained.
In order to further improve the shape stability of the resulting hydrous soft contact lens, the raw material monomer preferably contains a crosslinkable monomer having two or more polymerizable groups in the molecule.

Examples of the crosslinkable monomer include poly (meth) acrylates of polyhydric alcohols, polyurethane (meth) acrylates, and the like. Specifically, for example, ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, triethylene glycol Di (meth) acrylate, polyethylene glycol di (meth) acrylate, propylene glycol di (meth) acrylate, butylene di (meth) acrylate, dipentyl glycol di (meth) acrylate and other di (meth) acrylates, trimethylolpropane, pentaerythritol And a mixture of two or more of polyvalent esters of (meth) acrylic acid and the like.
The proportion in the case of incorporating the above-mentioned crosslinkable monomer into the raw material monomer is usually 0.1 to 10% by mass in the raw material monomer. If it is less than 0.1% by mass, the shape stability and the mechanical strength improving effect may not be obtained, and if it exceeds 10% by mass, the moisture content and flexibility of SCL may be lowered.

The raw material monomer preferably contains a monomer having a hydroxyl group in the molecule in order to improve operability by reducing the viscosity of the compound (1).
Examples of the monomer having a hydroxyl group in the molecule include 2-hydroxy (meth) acrylate, 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, 2-hydroxybutyl (meth) acrylate, 4-hydroxy Examples thereof include butyl (meth) acrylate, polyethylene glycol mono (meth) acrylate, glycerol (meth) acrylate, 2-hydroxyethyl (meth) acrylamide, hydroxyethyl vinyl ether, 4-hydroxybutyl vinyl ether, and 2- Preferred is hydroxyethyl (meth) acrylate.
The proportion of the raw material monomer containing the monomer having a hydroxyl group in the molecule is usually 5 to 95% by mass in the raw material monomer. If it is less than 5% by mass, the effect of improving the viscosity of the raw material monomer may not be obtained, and if it exceeds 95% by mass, the flexibility and fracture elongation of SCL may be reduced.

The raw material monomer includes the compound (1) alone, a mixture of the compound (1) and the crosslinkable monomer and / or the monomer having a hydroxyl group in the molecule, and other monomers capable of copolymerization other than these. It may be a mixture of
Examples of the other monomer include diethylaminoethyl (meth) acrylate, (meth) acryloyloxyethyl phosphate, 2- (meth) acryloyloxyethyl phosphorylcholine, methyl (meth) acrylate, ethyl (meth) acrylate, butyl ( (Meth) acrylate, octyl (meth) acrylate, allyl (meth) acrylate, glycidyl (meth) acrylate, dimethylaminoethyl (meth) acrylate, 2-methoxyethyl (meth) acrylate, fluorine-containing (meth) acrylate, silicon-containing (meta ) Various (meth) acrylic esters such as acrylate, various vinyl ethers such as methyl vinyl ether, N-vinylpyrrolidone, acrylamide, N, N'-dimethylacrylamide, (meth) acrylic acid, acrylonitrile, vinyl acetate, vinyl sulfone Sodium, styrene, chlorostyrene, itaconic acid, itaconic acid esters, fumaric acid, fumaric acid esters, maleic acid, one or more mixtures of various radical-polymerizable monomers such as maleic acid esters.
The proportion in the case where the other monomer is contained in the raw material monomer is arbitrary and can be selected as appropriate in order to obtain a desired effect. In order to bring out the performance of the compound (1), it is usually 40% by mass in the raw material monomer. Hereinafter, it is preferably 30% by mass or less.

In the present invention, the raw material monomer can be polymerized by radical polymerization or photopolymerization. The radical polymerization can be performed using a radical initiator.
Examples of the radical initiator include organic peroxides such as benzoyl peroxide and t-butylperoxyneodecanoate; 2,2′-azobisisobutyronitrile, dimethyl 2,2′-azobisisobutyrate and the like. An azo compound is mentioned.
As for the usage-amount of a radical initiator, 0.1-5.0 mass parts is preferable normally with respect to 100 mass parts of all the raw material monomers.
The polymerization temperature and the polymerization time can be appropriately selected and determined depending on the type of radical initiator, the presence or absence of other monomers, and the like. The polymerization temperature is preferably from room temperature to 150 ° C., and the polymerization time is suitably from about 0.1 to 48 hours, and a method of heating and cooling by programming is also selected if necessary.

The photopolymerization can be performed, for example, by irradiation with ultraviolet rays (UV) having a wavelength of 254 nm or electron beams (EB) having an acceleration voltage of 150 to 300 kV. In this case, the use of a photopolymerization initiator is optional, but it is preferably used from the viewpoint of reaction time.
Examples of the photopolymerization initiator include 2-hydroxy-2-methylpropiophenone and 1-hydroxy-cyclohexylphenylketone, and 2-hydroxy-2-methylpropiophenone is preferable from the viewpoint of solubility. Preferably mentioned.

  In order to prepare the SCL of the present invention, the raw material monomer is charged into, for example, a glass tube or a tube made of propylene or Teflon (registered trademark), a sheet, or a lens-shaped mold while being replaced with an inert gas or as it is. In the above polymerization conditions, radical polymerization or photopolymerization is performed to cure, and the resulting cured product is processed by machining. It can be prepared by treatment, immersion, and swelling with a water-soluble solvent.

Since the SCL of the present invention contains the above-mentioned polymer, the moisture content is usually 20% by mass or more, preferably 20 to 80% by mass, 35 ° C., and the oxygen permeability coefficient in physiological salt is usually 10 × 10 ⁻¹¹ cc. (STP) cm / cm ² · sec or more, preferably 15 to 30 × 10 ⁻¹¹ cc (STP) cm / cm ² · sec, the elastic modulus according to the test method shown in the examples described later is usually 0.2 MPa or more, preferably Is 0.3 to 0.8 MPa, the elongation to break by the test method shown in the examples described later is usually 250% or more, preferably 300% or more, and the antifouling resistance by the test methods shown in the examples described later is usually 10. 0 Pg / cm ² or less, preferably to meet all of the performance of 5.0 [mu] g / cm ² or less.

EXAMPLES Hereinafter, although an Example demonstrates this invention still in detail, this invention is not limited to these.
Synthesis example 1
To an eggplant-shaped flask, add 6.60 g of 2,3-o-isopropylideneglycerol and 1 ml of pyridine, weigh 7.37 g of methacryloyloxyethyl isocyanate (manufactured by Showa Denko KK), and add a dropping funnel and a calcium tube. Installed. Methacryloyloxyethyl isocyanate was slowly added dropwise at room temperature under light shielding. The reaction was carried out in an oil bath set at 50 ° C. for 7 hours. After completion of the reaction, pyridine and excess 2,3-o-isopropylideneglycerol were distilled off under reduced pressure to yield 12.7 g, 93% yield of 2,3-o-isopropylideneglyceryl-1 as a white solid. -Methacryloyloxyethyl urethane was obtained. The measurement result of ¹ H-NMR is shown below.
¹ H-NMR (CDCl ₃ ) 1.3-1.5 ppm, d, C H ₃ (6H) 1.9 ppm, s, CH ₂ = CH (C H ₃ ) (3H) 3.4-4.4 ppm, m, OC H ₂ C H ₂ NH C H ₂ C H C H ₂ (9H) 5.1 ppm, s, N H (1H) 5.6, 6.1 ppm, s, C H ₂ = C (CH ₃ ) (2H)
Next, 3.9 ml of methanol and 100 μl of 4N hydrochloric acid were added to 1.0 g of the obtained 2,3-o-isopropylideneglyceryl-1-methacryloyloxyethylurethane, and the mixture was stirred at room temperature for 30 minutes. Became a clear solution. The mixture was further stirred for 60 minutes and then dried under reduced pressure to obtain a colorless viscous liquid glyceryl-1-methacryloyloxyethylurethane (hereinafter abbreviated as GMU) in a yield of 852 mg. The measurement result of ¹ H-NMR is shown below.
¹ H-NMR (D ₂ O) 1.8 ppm, s, CH ₂ = CH (C H ₃ ) (3H) 3.3-4.2 ppm, m, OC H ₂ C H ₂ NH C H ₂ C H C H ₂ (9H) 5.6, 6.0 ppm, s, C H ₂ = C (CH ₃ ) (2H)
The obtained product was HPLC (eluent: water / acetonitrile = 4/6 (v / v), column: ODS, detector: UV (220 nm), liquid feed rate: 1.0 ml / min, column bath temperature: 40 ° C.), the glyceryl-1-methacryloyloxyethyl urethane obtained was found to have a purity of 98% or more.

Synthesis example 2
The same operation as in Synthesis Example 1 was performed except that 2,3-o-isopropylideneglycerol (-monopolyethylene glycol was used instead of 2,3-o-isopropylideneglycerol, yield 21.3 g, yield 96% Thus, white solid 2,3-o-isopropylideneglycerin (-monopolyethylene glycol-1-methacryloyloxyethylurethane was obtained. The results of ¹ H-NMR measurement are shown below.
¹ H-NMR (CDCl ₃ ) 1.3-1.5 ppm, d, C H ₃ (6H) 1.9 ppm, s, CH ₂ = CH (C H ₃ ) (3H) 3.4-4.5 ppm, m, OC H ₂ C H ₂ NH (C H ₂ C H ₂ O) ₄₈ C H ₂ C H C H ₂ (201H) 5.1 ppm, s, N H (1H) 5.6, 6.1 ppm, s , C H ₂ = C (CH ₃ ) (2H)
The product 2,3-o-isopropylideneglycerin (-monopolyethyleneglycol-1-methacryloyloxyethylurethane) was then used in the same manner as in Synthesis Example 1, except that a white solid having a yield of 831 mg was obtained. Glyceryl (-monopolyethyleneglycol-1-methacryloyloxyethylurethane (hereinafter abbreviated as PEMU) was obtained. The measurement results of ¹ H-NMR are shown below.
¹ H-NMR (D ₂ O) 1.9 ppm, s, CH ₂ ═CH (C H ₃ ) (3H) 3.4-4.4 ppm, m, OC H ₂ C H ₂ NH (C H ₂ C H ₂ O) ₄₈ C H ₂ C H C H ₂ (201H) 5.1 ppm, s, N H (1H) 5.6, 6.1 ppm, s, C H ₂ = C (CH ₃ ) (2H)
Furthermore, as a result of analyzing the obtained product by HPLC in the same manner as in Synthesis Example 1, it was found that the purity of the obtained glyceryl (-monopolyethyleneglycol-1-methacryloyloxyethylurethane was 96% or more.

Example 1
As a raw material monomer, 19.0 g of GMU prepared in Synthesis Example 1 and 1.0 g of triethylene glycol dimethacrylate and 0.1 g of t-butylperoxypivalate as a radical initiator were injected into a test tube mold, After repeating nitrogen substitution and deaeration, it was sealed and heat-cured. Heating was performed by heating from 40 ° C. to 120 ° C. for 50 hours in a thermostatic bath, and a colorless and transparent polymer was obtained after completion of curing. The obtained polymer was subjected to normal cutting and polishing, and further immersed in physiological saline to obtain swollen SCL. The obtained SCL was evaluated as follows. The results are shown in Table 1.
<Moisture content>
The weight in the saturated water-containing state was W1 and the weight in the dry state was W2, and calculated from (W1-W2) / W1 × 100 (mass%).
<Oxygen transmission coefficient>
The oxygen permeation coefficient was measured in physiological saline at 35 ° C. using a Seikaken type film oxygen permeation measuring device.
<Elastic modulus, breaking elongation>
An arrayed flat plate with a narrowed center was immersed in a physiological saline solution at 20 ° C. as a test piece, and then tested at a speed of 60 mm / min. The elastic modulus was calculated using the stress when the elongation was 2%, and the breaking elongation was the elongation at break.
<Anti-fouling resistance>
SCL was placed in a physiological saline solution containing 0.5% by weight of egg white lysozyme, treated at 60 ° C. for 2 hours, washed with physiological saline, then measured for UV absorbance at 280 nm, and the amount of adsorbed protein was measured.

Example 2
Except that GMU in the raw material monomer was changed to PEMU, the same operation as in Example 1 was performed to obtain a colorless and transparent polymer, which was swollen to obtain SCL. The obtained SCL was evaluated in the same manner as in Example 1. The results are shown in Table 1.

Example 3
Test tube containing 12.0 g of GMU as a raw material monomer, 7.9 g of 2-hydroxyethyl methacrylate (hereinafter abbreviated as HEMA) and 0.1 g of allyl methacrylate, and 0.1 g of t-butylperoxypivalate as a radical initiator Except for pouring into the mold, the same operation as in Example 1 was performed to obtain a colorless and transparent polymer, which was swelled to obtain SCL. The obtained SCL was evaluated in the same manner as in Example 1. The results are shown in Table 1.

Example 4
The same procedure as in Example 1 was performed, except that a mixture of GMU 6.0 g, HEMA 13.9 g, and ethylene glycol dimethacrylate (hereinafter abbreviated as EGMA) 0.1 g was used as a raw material monomer. After obtaining, swollen SCL was obtained. The obtained SCL was evaluated in the same manner as in Example 1. The results are shown in Table 1.

Example 5
Part of a mixture of GMU 12.0 g, HEMA 7.9 g, allyl methacrylate 0.1 g and 2-hydroxy-2-methylpropiophenone 0.05 g as a photopolymerizer as raw material monomers is made of quartz glass. In addition to the transmission cell, UV light was irradiated for 2 minutes using a 400 W high-pressure mercury lamp in an argon atmosphere. Using the obtained polymer, it processed like Example 1 and produced SCL, Then, performance evaluation was performed. The results are shown in Table 1.

Examples 6-8
Except for using PEMU instead of GMU, curing polymerization was performed in the same manner as in Examples 3 to 4, and performance evaluation was performed. The results are shown in Table 1.

Comparative Examples 1-4
Comparative Examples 1, 2 and 4 were obtained in the same manner as in Example 1, and Comparative Example 3 was obtained in the same manner as in Example 5. SCL was fabricated and performance was evaluated. The results are shown in Table 2.

Claims (2)

A hydrous soft contact lens comprising a polymer obtained by polymerizing a raw material monomer containing a urethane bond-containing diol (meth) acrylate compound represented by the formula (1).

(Wherein R ₁ represents a hydrogen atom or a methyl group, R ₂ represents a group represented by — (CH ₂ ) n —, and R ₃ represents a group represented by — (CH ₂ ) m —, where n is 1-4 and m are integers of 1 to 8. AO is an oxyalkylene group having 2 to 4 carbon atoms, and x is an integer of 0 to 1000.) The hydrous soft contact lens according to claim 1, wherein the raw material monomer includes a crosslinkable monomer having two or more polymerized groups in the molecule and / or a monomer having a hydroxyl group in the molecule.