JPS61197609A - Fluorine-containing polymer and medical oxygen-permeable body - Google Patents

Abstract

PURPOSE:A fluorine-containing polymer which can give an oxygen-permeable body, such as a hard contact lens, excellent in oxygen permeability, ultraviolet resistance, high surface hardness, hydrophilicity, stain resistance, etc., prepared from a fluorine-containing methacrylate ester. CONSTITUTION:A fluorine-containing polymer for the production of a medical oxygen-permeable body, obtained by copolymerizing 5-60wt% fluorine- containing methacrylate ester of formula I [wherein R is phenyl, pentafluorophenyl or cyclohexyl and Rf is a group of formula II (wherein n is 0 or 1-8), or pentafluorophenyl], e.g., 1-phenyl-2,2,2-trifluoroethyl methacrylate, with 5-10wt% hydrophilic monomer (e.g., 2-hydroxyethyl methacrylate), 20-55wt% silicon-containing methacrylate ester [e.g., 3-(methacryloxy)propyltrimethoxy-silane], 0-34wt% methyl or ethyl methacrylate and 1-10wt% methacrylic acid derivative having at least two polymerizable functional groups (e.g., ethylene glycol dimethacrylate).

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Application] The present invention relates to a fluorine-containing polymer having oxygen permeability and a medical oxygen permeable body made of the polymer.

Specifically, when it is desired to continuously supply oxygen to tissues, it is possible to supply oxygen without using biological fluids (e.g. blood) that are unstable to oxygen loading that requires physical agitation etc. The present invention relates to a fluorine-containing polymer having oxygen permeability and a medical oxygen permeable body made of the polymer.

More specifically, the present invention relates to a fluorine-containing polymer having oxygen permeability useful as a raw material for manufacturing oxygen permeable materials such as ophthalmic materials such as hard contact lenses (HCL), and medical oxygen permeable materials made of the polymer.

[Prior art]

Conventionally, polymethylmethacrylate-1-(PMMA) has been widely used as a material for HCL and the like due to its excellent optical properties, chemical properties, physical strength, and mechanical processability.

By the way, since the cornea is an avascular tissue, only a small amount of light is absorbed by diffusion from the conjunctival blood vessels and the aqueous humor, but when the eye is open, it is taken in from the atmosphere. Therefore, HCL
Wearing the cornea creates an oxygen barrier and can cause hyperemia, edema, and other corneal damage. The amount of oxygen required by the cornea is 3.5 to 4.8 pg.
(STP)/crA, hr.

Since the conventional PMMA-based HCL has very low oxygen permeability, it has been desired to develop an oxygen permeable material such as HCL with high oxygen permeability. Under these circumstances, in recent years, silicone methacrylate-based HCL (Japanese Patent Publication No. 33502/1983) has been developed, which improves oxygen permeability by introducing a siloxane bond into the ester moiety of methacrylic acid ester, and oxygen permeability based on cellulose acetate butyrate (CAB). oxygen-permeable HCL using fluorine-containing methacrylate
(Japanese Unexamined Patent Publication No. 57-51705) is disclosed. The silicone methacrylate-based HCL disclosed in Japanese Patent Publication No. 52-33502 is generally different from the conventional PMMA-based HCL.
It has an oxygen permeability tens to hundreds of times higher than that of
Since it is inferior in hardness and hydrophilicity, it has the disadvantage of being easily contaminated with lipids and the like.

For this reason, it is generally in the form of a copolymer with methyl methacrylate (MMA), but as the proportion of silicone methacrylate increases, oxygen permeability improves, but the drawbacks mentioned above become more noticeable. (Ru.

In addition, soft contact lenses are also susceptible to contamination by bacteria and fungi, contamination by tear fluid components (proteins, lipids, mucin, etc.), cumbersome cleaning, contamination by cigarette smoke and cosmetics such as mascara, and yellowing. There are problems such as cloudiness and short lifespan.

On the other hand, fluorine-containing polymers have corrosion resistance, are resistant to dirt, and have high permeability to oxygen and carbon dioxide.Using these properties, HCL with high oxygen permeability can be produced from copolymers of fluorine-containing monomers. has already been found, but in addition, oxygen permeation h・−=−JL Noh h1 indoor JJ+−
There is a long-awaited need for oxygen permeable materials such as HCL that have excellent on-visitability and polymers for producing such oxygen permeable materials.

[Problem that the invention seeks to solve]

An object of the present invention is to provide an oxygen permeable material such as HCL that has excellent oxygen permeability, ultraviolet resistance, high surface hardness, hydrophilicity, antifouling property, etc.

Another object of the present invention is to provide a fluorine-containing polymer useful for producing the oxygen permeable body.

c. Means for Solving Problems] The present inventors have conducted extensive research in order to achieve the above object. As a result, -S formula (I): [wherein R represents a phenyl group, a pentafluorophenyl group, or a cyclohexyl group, and Rf represents a formula% (where n=o or an integer from 1 to 8)] or a pentafluorophenyl group] A fluorine-containing polymer prepared from a fluorine-containing methacrylic acid ester (I) represented by the following, particularly 5 to 60% by weight of the fluorine-containing methacrylic acid ester (■), Hydrophilic monomer 5 to IO weight %, silicon-containing methacrylic acid ester 20
~55% by weight, 0-3 methyl or ethyl methacrylate
4% by weight and 1 to 10% by weight of methacrylic acid derivative as a crosslinking agent having two or more polymerizable functional groups.
When producing L), the inventors found that the above-mentioned object could be easily achieved, leading to the completion of the present invention.

That is, the present invention relates to a fluorine-containing polymer prepared using the fluorine-containing methacrylic acid ester (1), and a medical oxygen permeable body made of the fluorine-containing polymer.

Regarding Rf in general formula (I), -(CF!)n-C
n in FI is O or an integer of 1 to 8, particularly preferably 0 to 3.

Fluorine-containing methacrylic ester (1) of the present invention, 5 to 60% by weight of tacrylic ester (1), 5 to 1% hydrophilic monomer
0% by weight, silicon-containing methacrylic acid ester 20-55% by weight, methyl or ethyl methacrylate 0-34% by weight,
and a copolymer obtained by polymerizing 1 to 10% by weight of a methacrylic acid derivative having two or more polymerizable functional groups.

The silicon-containing methacrylic acid ester used in the present invention is used to further increase oxygen permeability. In our industry, examples of methacrylic acid esters having a siloxane bond include 3-(methacryloxy)propyltrimethoxysilane, 3-(methacryloxy)propylbis(trimethylsiloxy)methylsilane, and 3-(methacryloxy)propyldimethoxymethylsilane. ,3
-(methacryloxy)propyltris(trimethylsiloxy)silane, etc., and the amount used thereof is in the range of 20 to 55% by weight based on the resulting copolymer.

The hydrophilic monomer used in the present invention increases hydrophilicity by containing fluorine or a silicon compound, and is therefore used to impart hydrophilicity. As a hydrophilic monomer,
Any device having such a function and meeting the purpose of the present invention can be suitably used. Preferred examples of such hydrophilic monomers include those having a structure such as -0H1-COOHlN, specifically 2-hydroxyethyl methacrylate, polyethylene glycol monomethacrylate, glyceryl methacrylate, N-vinylpyrrolidone, Examples include methacrylic acid and dimethylacrylamide. The amount of hydrophilic monomer used is in the range of 5 to 10% by weight based on the resulting copolymer.

Furthermore, the methacrylic acid derivative having two or more polymerizable functional groups used in the present invention is a crosslinking agent and is used to improve processability and dimensional stability of the lens. The methacrylic acid derivatives include ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate,
Tetraethylene glycol dimethacrylate, allyl methacrylate, trimethylolpropane trimethacrylate, l,3-butylene glycol dimethacrylate,
Examples include pentaerythritol tetramethacrylate, and the amount of these used varies.

The amount ranges from 1 to 10% by weight based on the copolymer.

Furthermore, methyl methacrylate or ethyl methacrylate is used to maintain hardness and facilitate molding, and is preferably used in a range of 0 to 34% by weight. Too little of these makes the polymer soft, while too much makes it hard and brittle.

In producing the polymer or copolymer of the present invention, a free radical polymerization initiator commonly used in the polymerization of unsaturated hydrocarbon compounds is used. Examples of the polymerization initiator include hensyl peroxide, lauroyl peroxide, t-butyl peroxide, abbisisobutyronitrile, and azobisdimethylvaleronitrile. The range of 0.01 to 1% by weight is desirable. Although various types of polymerization can be employed, bulk polymerization is particularly preferred in the present invention.

The novel polymer or copolymer obtained as described above has an oxygen permeability of 5 to 70X, which is significantly improved compared to the conventional polymethyl methacrylate oxygen permeable material.
10-'' cc, cm/a (, sec, m+mHg), and the Vickers hardness was also good at 7-20.

The oxygen permeability coefficient was measured using a Seikan Irum oxygen permeability meter on a disc-shaped film with a diameter of 17.5 wi and a thickness of 0.2 fl. Measurement temperature is 35℃
It is. Hardness was measured using a Vickers hardness tester.

The fluorine-containing methacrylic acid ester (1) is prepared by combining, for example, a reactive derivative of methacrylic acid, preferably a halide of methacrylic acid, more preferably a methacrylic acid chloride, and the general formula % formula % () (in the formula, R and Rf is produced by reacting with a fluorine-containing alcohol (n) represented by (same meaning as above). This reaction is preferably carried out in the presence of a base such as triethylamine.

C)13 (wherein R and Rf have the same meanings as above) The fluorine-containing alcohol (II) is, for example, J, And.

CheIll, Soc, + vol. 78, p. 2268 (1
956), a carboxylic acid obtained from the corresponding fluorine-containing carboxylic acid and a phenyl Grignard reagent, a pentafluorophenyl Grignard reagent, or a cyclohexyl Grignard reagent using a reducing agent such as sodium borohydride. It can be obtained by reducing the

Alternatively, it can be synthesized directly from a fluorine-containing Grignard reagent and an aldehyde.

Next, the present invention will be explained in more detail with reference to Examples and Reference Examples.

Reference Example 1: Synthesis of 1-phenyl-2,2,2-)lifluoroethyl methacrylate A 11-necked flask equipped with a stirrer, a thermometer, a dropping funnel, a nitrogen gas introduction tube, and a reflux condenser was replaced with nitrogen, A phenyl Grignard reagent was prepared from 48 g of magnesium, 314 g of bromobenzene, and 500 ml of ether, and 76 g of trifluoroacetic acid was added dropwise at 5 to 10°C.

The mixture was stirred overnight and worked up with 500ml of diluted hydrochloric acid. After extraction with ether and washing, it was dried and concentrated under reduced pressure. 20 g of phosphorus pentachloride was added and distilled. bp 150-1
54℃, 71g, 11? 1720 cm' (ketone). IR1'H-NMR119F of the obtained liquid
The spectral data and physical properties such as -NMR were consistent with the reported values for phenyl trifluoromethyl ketone (
K, T, Dishart and R, Levine
.

J, Am, Chem, Soc,, 78.2268 (
1956) ), the ketone thus obtained was placed in a similar two-headed flask apparatus with sodium borohydride 8,
2 g and 150 ml of ethanol at 0° C. or lower. The mixture was left to stand overnight, worked up with 20 ml of concentrated hydrochloric acid, extracted with ether, washed, dried, concentrated under reduced pressure, and then distilled.

bp 100~104 (40mml1g) 'C1
60 g, which shows absorption based on hydroxyl group at 3400 cs-' in IR, and 1-7-diru2.2.2-
) was shown to be trifluoroethyl alcohol. The alcohol thus obtained was placed in a similar two-headed flask apparatus, 53.1 g of triethylamine was added at below 10°C, and 54.7 g of methacrylic acid chloride was added at 10 to 30°C.
g of chloroform solution (280II11) was added dropwise.

The mixture was heated and stirred at room temperature for 3 hours and then for a further 6 hours. water 30
After adding 0 ml of the solution, the solution was separated, washed, dried, and concentrated under reduced pressure. 0.15 g of hydroquinone was added and distilled. bp
78-81 (4mmh)'C168,6g, this one has a ketone-based absorption at 1730 low 1 in Summer R.
1634 value - absorption based on double bonds is 700 and 948
A characteristic absorption indicating monosubstituted benzene was observed in the cffi-'Si region. 19 F-NMR is 7
dd signal at 5.2 ppm (CFCl3), 2.0 (3H), 5.7 (I
H), 6.3 (IH), 7.4
A signal was confirmed at ppm (5H). In elemental analysis, experimental values: C; 59.24%, H; 4.36
%, calculated value: Cl2H.

02 For F3, C; 59.01%, H; 4.5
Obtained 4%. From the above, the main island is 1-phenyl-2
, 2゜2-trifluoroethyl methacrylate.

Reference Example 2: Synthesis of 1,1-bis(pentafluorophenyl)methyl methacrylate Decafluorobenzhydryl (100g), dry! Triethylamine (300g) and dry benzene (500g)
m1), add methacrylic acid chloride (450g)
A benzene solution (500 ml) of was gradually added dropwise over 8 hours while stirring at room temperature. After the dropwise addition, the mixture was refluxed for 15 hours, and after cooling, the reaction solution was poured into ice water 2z, and the organic layer was separated. For the aqueous layer, shake with benzene 200ml x 200ml.
2) Combine the organic layer and benzene layer and wash with dilute hydrochloric acid and saturated NaHCO3 aqueous solution in that order.
wl X 2 ) and dried over anhydrous magnesium sulfate. After evaporation of the solvent, the residue was evaporated with H,C,5till.
et al. J. Org. Chem., 43
゜2923 (197B) ), pale yellow liquid 10
5g was obtained.

Since Honjima easily polymerizes, add an appropriate amount of polymerization inhibitor and store it refrigerated. The main island is, I R (Iiq, ■-
1), 2975.2930 (CH), 1735
(C=O), 1655 (C=C), and 19F-NMR (CFCI3, pPII
I), 140.2 (2F), 151.5 (
IF), 160.3 (2F) gave a signal supporting the pentafluorophenyl group, 'H-NMR (
TMS, I)I)m), 2.0 (3H),
5.7 (LH), 6.3 (IH), '7.4
(IH) showed absorption. Based on the above instrumental analysis data and elemental analysis results, Motojima was determined to be 1.1-bis(pentafluorophenyl)methyl methacrylate.

Example 1 1.6 g of 1-phenyl-2,2,3,3,3-pentafluoropropyl methacrylate, 0.2 g of 2-hydroxyethyl methacrylate, 3-(methacryloxy)propyldimethoxymethylsilane 1. Og, methyl methacrylate 1.0g, ethylene glycol dimethacrylate 0.2g and azobisisobutyronitrile 20+ng
After mixing well, the mixture was polymerized by heating at 50°C for 24 hours, at 60°C for 3 hours, and at 80°C for 5 hours to obtain a colorless and transparent material. The oxygen permeability coefficient of this material is 7. OX 10-11
cc, cm/aa, sec, m+nHg.

V, Kaas hardness Nl 12. It was O. HCL was created using this equipment.

Example 2 1.6 g of 1-cyclohexylpentafluorohensyl methacrylate, 0.2 g of N-vinylpyrrolidone, 3-(
Methacryloxy)propylbis(trimethylsiloxy)methylsilane 0.8g, methyl methacrylate 1.4g
, 0.2 g of allyl methacrylate, and 1 g of azobisdimethylvaleronitrile 20II were thoroughly mixed and treated in the same manner as in Example 1 to obtain a slightly yellow transparent material. The oxygen permeability coefficient is 5. Ox l O” cc, cm/cf
fl, sec, mmHg %Vinocurs hardness 1k14
．． It was 0. HCL was prepared using this equipment.

Example 3 1.2.0 g of 1-bis(pentafluorophenyl)methyl methacrylate, 0.2 g of polyethylene glycol monomethacrylate, 3-(methacryloxy)propylbis(trimethylsiloxy)methylsilane1. Og,
After thoroughly mixing 1.5 g of methyl methacrylate, 0.2 g of ethylene glycol dimethacrylate, and 20 mg of azobisisobutyronitrile, the mixture was treated in the same manner as in Example 1 to obtain a yellow transparent material. The oxygen permeability coefficient is 7.
OX 10" cc, cm/cJ, sec, 'mmH
'g, and the Vinocas hardness was 11ia 13.0. HCL was created using this equipment.

Example 4 1.1-bis(pentafluorophenyl)methyl methacrylate 2.0 g, methacrylic MO, 2 g.

1.5 g of 3-(methacryloxy)propyl tris(trimethylsiloxy)silane, 1. methyl mecrylate.
After thoroughly mixing 0.2 g of ethylene glycol dimethacrylate and 20 mg of azobisisobutyronitrile, the mixture was treated in the same manner as in Example 1 to obtain a pale yellow transparent material. The oxygen permeability coefficient of this equipment is 25. OX10”
cc, cm/cnl, sec, mm 11g, Vinokase hardness Th 12.5. HCL was created using this equipment.

Claims (14)

[Claims] (1) General formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R is a phenyl group, pentafluorophenyl group, or cyclohexyl group, and Rf is the formula -(CF_2)_n-CF_3 (However, n=0 or an integer of 1 to 8) or a pentafluorophenyl group] A fluorine-containing polymer prepared from a fluorine-containing methacrylic acid ester represented by the following. (2) 5 to 60% by weight of a fluorine-containing methacrylic acid ester having the general formula (I), 5 to 10% by weight of a hydrophilic monomer,
20 to 55% by weight of silicon-containing methacrylic acid ester, 0 to 34% by weight of methyl or ethyl methacrylate, and methacrylic acid derivatives 1 to 1 having two or more polymerizable functional groups.
A fluorine-containing polymer obtained by polymerizing 10% by weight. (3) The hydrophilic monomer is at least one selected from the group consisting of 2-hydroxyethyl methacrylate, polyethylene glycol monomethacrylate, glyceryl methacrylate, N-vinylpyrrolidone, methacrylic acid, and dimethylacrylamide. The fluorine-containing polymer described in section 2). (4) The silicon-containing methacrylic acid ester is 3-(methacryloxy)propyltrimethoxysilane, 3-(methacryloxy)propylbis(trimethylsiloxy)methylsilane, 3-(methacryloxy)propyldimethoxymethylsilane, 3-(methacryloxy)propyltrimethoxysilane, 3-(methacryloxy)propylbis(trimethylsiloxy)methylsilane, The fluorine-containing polymer according to claim (2), which is at least one member selected from the group consisting of oxy)propyltris(trimethylsiloxy)silane. (5) The methacrylic acid derivative having two or more polymerizable functional groups is ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, allyl methacrylate, trimethylolpropane trimethacrylate, 1, Claim No. 2 which is either 3-butylene glycol dimethacrylate or pentaerythritol tetramethacrylate
) The fluorine-containing polymer described in section 2. (6) at least one free radical polymerization initiator used in the polymerization of unsaturated hydrocarbon compounds;
The seed polymerization initiator is added to the monomer mixture for polymerization at a rate of 0.0
The medical fluorine-containing polymer according to claim (2), which is used in a proportion of 1 to 1% by weight. (7) Oxygen permeability coefficient 5-70 x 10^-^1^1cc.
cm/cm^2. sec. mmHg, Vickers hardness N
o. 7 to 20. The fluorine-containing polymer according to claims (1) to (6). (8) General formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R is a phenyl group, pentafluorophenyl group, or cyclohexyl group, and Rf is the formula -(CF_2)_n-CF_3 (However, n = 0 or an integer of 1 to 8) or a pentafluorophenyl group] A fluorine-containing polymer prepared by a fluorine-containing methacrylic ester represented by Medical oxygen permeable body. (9) 5 to 60% by weight of a fluorine-containing methacrylic ester having general formula (I), 5 to 10% by weight of a hydrophilic monomer, 20 to 55% by weight of a silicon-containing methacrylic ester, 0 to 50% of methyl or ethyl methacrylate 34% by weight, and methacrylic acid derivatives 1-1 having two or more polymerizable functional groups
The medical oxygen permeable body according to claim (8), comprising a fluorine-containing polymer obtained by polymerizing 0% by weight. (10) The hydrophilic monomer is 2-hydroxyethyl methacrylate, polyethylene glycol monomethacrylate,
Claim No. 9, which is at least one member selected from the group consisting of glyceryl methacrylate, N-vinylpyrrolidone, methacrylic acid, and dimethylacrylamide.
A medical oxygen permeable material comprising the fluorine-containing polymer described in 1. (11) The silicon-containing methacrylic acid ester is 3-(methacryloxy)propyltrimethoxysilane, 3-(methacryloxy)propylbis(trimethylsiloxy)methylsilane, 3-(methacryloxy)propyldimethoxymethylsilane, 3-(methacryloxy)propyltrimethoxysilane, 3-(methacryloxy)propylbis(trimethylsiloxy)methylsilane, A medical oxygen permeable body made of a fluorine-containing polymer according to claim 9, which is at least one member selected from the group consisting of oxy)propyltris(trimethylsiloxy)silane. (12) The methacrylic acid derivative having two or more polymerizable functional groups is ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, allyl methacrylate, trimethylolpropane trimethacrylate, 1, Claim No. 3, which is either 3-butylene glycol dimethacrylate or pentaerythritol tetramethacrylate (
A medical oxygen permeable material comprising the fluorine-containing polymer according to item 9). (13) In the polymerization, at least one polymerization initiator selected from free radical polymerization initiators used in the polymerization of unsaturated hydrocarbon compounds is added to the monomer mixture for polymerization at a rate of 0.
A medical oxygen permeable body made of a medical fluorine-containing polymer according to claim (9), which is used in a proportion of 0.01 to 1% by weight. (14) Oxygen permeability coefficient 5-70 x 10^-^1^1cc
．． cm/cm^2. sec. mmHg, Vickers hardness No. A medical oxygen permeable body made of a fluorine-containing polymer according to claims (8) to (13), characterized in that it is a fluorine-containing polymer.