JPH0654900A - Intraocular lens coated with plasma-polymerized film - Google Patents

Abstract

PURPOSE:To assure excellent bioaffinity and to recover sight in an early period after the operation by coating the surface of a transparent lens base body with a plasma-polymerized film which consists substantially of carbon, hydrogen, halogen and oxygen and having an average compsn. of specific atom ratios. CONSTITUTION:The surface of the transparent lens base body of the intraocular lens used in operation of cataract, etc., is so treated as to be coated with the plasma-polymerized film which consists substantially of respective atoms of carbon C, hydrogen H, halogen X and oxygen O, has the average compsn. of the atom ratios expressed by (formula) and has 0 to 0.1 ratio of the bonded hydrogen atoms to the carbon atoms having the double bonds to the number of the hydrogen atoms to be single bonded. The plasma-polymerized film is formed by arranging the lens base body into specific gas contg. respective monomer compds. of, for example, alkane halide, alkane, hydrogen or halogen and subjecting the gas to a plasma polymn. As a result, the intraocular lens which can restore the sight in the early period after the operation is obtd.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a plasma polymerized film-coated intraocular lens, and more particularly, it is inserted after a cataract operation, which is coated with a plasma polymerized film consisting essentially of carbon, hydrogen, halogen and oxygen. Regarding intraocular lenses.

[0002]

2. Description of the Related Art The human lens is opaque due to various factors such as trauma, diabetes or aging, which causes
May cause significant loss or loss of vision. Such diseases are collectively referred to as cataracts, but as a treatment method for this cataract, in addition to a method of surgically removing the cloudy lens and then inserting an intraocular lens made of a transparent base material, A method of surgically removing an opaque lens and wearing contact lenses or glasses without inserting an intraocular lens has been performed. Of these treatments,
In the latter method of wearing contact lenses and eyeglasses without inserting the intraocular lens, since the wearing position of the contact lenses and eyeglasses is different from the original position of the crystalline lens, the corrected visual acuity is far from the original one. It is inevitable that it will cause great inconvenience in the postoperative life of cataract patients.
Therefore, a treatment method of inserting an intraocular lens after extraction of the lens is generally performed today, except for special cases. This is because it is possible to insert the intraocular lens into the original position of the crystalline lens, and the image on the retina is almost normal, so that it is possible to provide the patient with good visual acuity recovery after surgery. Further, the intraocular lens once inserted is basically different from contact lenses in that daily management is unnecessary. As a transparent substrate for the intraocular lens, polymethylmethacrylate resin (hereinafter referred to as "PMMA resin") is generally used at present. This conventionally used PMMA resin intraocular lens has excellent optical characteristics and can generally obtain a good therapeutic effect, but on the other hand, after being inserted into the eye, various intraocular lenses are formed. There is a case where foreign matter is adhering, and this adhering foreign matter is also a major factor that hinders the recovery of visual acuity after surgery. The types of such foreign substances are diverse, and examples thereof include cell components such as macrophages, foreign substance giant cells, and fibroblast-like cells derived from intraocular inflammation, and biological components such as proteins in the aqueous humor. Regarding the types of these foreign substances and the amount of deposits, it is said that the material, shape, surface texture, etc. of the intraocular lens are related, and the interaction between these factors and cells such as lens epithelial cells and lymphocytes in the aqueous humor. It is believed that this causes post-operative inflammation and accelerates the attachment of the above-mentioned cellular components and biological components. Of these factors, the properties of the surface of the intraocular lens are particularly important as factors affecting the adhesion of cell components and biological components at the same time as affecting the opacity of the lens capsule after insertion of the intraocular lens. Improvement studies have been attempted. For example, a heparin surface-modified intraocular lens in which the surface of the intraocular lens is coated with heparin, or the surface is inactivated by a special chemical reaction (s
A surface-passivated intraocular lens has been developed and put into use. In addition, an intraocular lens in which a PMMA resin surface is coated with a diamond-like carbon film by plasma-polymerizing an alkane such as methane has also been proposed (for example, JP-A-63-203163,
See NEW DIAMOND, 7 (3), 21-25). However, with the increase in the number of cases to be applied and a request to improve the therapeutic effect, for the intraocular lens, the present situation is that further improvement is required for the convenience of surgery, biocompatibility, etc. In addition, since the carbon film of the intraocular lens coated with the diamond-like carbon film is fragile, great care must be taken in handling before and during surgery.

[0003]

SUMMARY OF THE INVENTION Therefore, the object of the present invention is to improve the biocompatibility of an intraocular lens inserted after a cataract surgery, especially by improving the properties of the surface of the lens substrate. An object of the present invention is to provide an intraocular lens that can suppress the adhesion of cell components and biological components to the lens surface and bring about good visual acuity recovery in the early postoperative period.

[0004]

That is, according to the present invention, the surface of a transparent lens substrate is substantially composed of carbon (C), hydrogen (H), halogen (X) and oxygen (O) atoms. , And the ratio of the number of hydrogen atoms bonded to a carbon atom having a double bond to the number of hydrogen atoms bonded to a carbon atom having only a single bond, which has an average composition of the atomic ratios shown below, is 0 to 0. The present invention relates to an intraocular lens coated with a plasma-polymerized film of 1.

[Chemical 1]

Here, a hydrogen atom bonded to a carbon atom having only a single bond is represented by the formula

[Chemical 2] And a hydrogen atom bonded to a carbon atom having a double bond is represented by the formula:

[Chemical 3] Means a hydrogen atom represented by.

In the present invention, the plasma-polymerized film coating the surface of the transparent lens substrate is composed of, for example, a halogenated alkane (a), alkane (b), hydrogen (c) or halogen (d) monomer compound. From (1) below
A gas containing a component selected from any combination of (10), wherein the ratio of the total number of halogen atoms / the total number of hydrogen atoms in the gas is 0.1 to 5 in the plasma polymerization zone. It can be formed by placing a lens substrate and plasma polymerizing the gas. (1) Only a (except when a is a perfluoroalkane); (2) a and b; (3) a and c; (4) a and d; (5) a, b and c; 6) a, b and d; (7) a, c and d; (8) a, b, c and d; (9) b and d; (10) b, c and d.

In the present invention, the above (1) to (10)
Selection of the combination, the gas composition conditions such as the ratio between the respective monomer compounds in the case of combining two or more monomer compounds (2) to (10) are determined according to the desired average composition of the plasma polymerized film. The appropriate gas composition conditions can be set by experiments.

In the present invention, any of the monomer compounds a to d can be used as long as they are in a gaseous state under the plasma polymerization conditions described later.

The halogenated alkane is a compound in which at least one hydrogen atom of an alkane, that is, a saturated aliphatic hydrocarbon is substituted with at least one halogen atom selected from a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. , Preferred halogenated alkane has 1 carbon atom
To 4, more preferably 1 to 2 carbon atoms.

As such a halogenated alkane,
For example, monofluoromethane, difluoromethane, trifluoromethane, tetrafluoromethane, monochloromethane, dichloromethane, trichloromethane, tetrachloromethane, monofluoromonochloromethane, monofluorodichloromethane, monofluoroethane, difluoroethane, trifluoroethane, tetrafluoroethane, Pentafluoroethane, hexafluoroethane, monochloroethane, dichloroethane, trichloroethane, tetrachloroethane, pentachloroethane, hexachloroethane, monofluoromonochloroethane, monofluorodichloroethane, difluoromonochloroethane, difluorodichloroethane, trifluoromonochloroethane, trifluorodichloroethane, Trifluorotrichloroethane, monofluoro Bread, difluoropropane, trifluoropropane, tetrafluoropropane, pentafluoropropane, hexafluoropropane, perfluoropropane, monochloropropanediol, dichloropropane,
Trichloropropane, tetrachloropropane, pentachloropropane, hexachloropropane, perchloropropane, monofluoromonochloropropane, monofluorodinochloropropane, difluoromonochloropropane,
Difluorodichloropropane, trifluoromonochloropropane, trifluorodichloropropane, tetrafluoromonochloropropane, tetrafluorodichloropropane, monofluoro n-butane, difluoro n-butane, trifluoro n-butane, tetrafluoro n-butane, pentafluoro n- Butane, hexafluoron-butane, octafluoron-butane, monofluoroisobutane, difluoroisobutane, trifluoroisobutane, tetrafluoroisobutane, pentafluoroisobutane, hexafluoroisobutane, octafluoroisobutane, monochloron-butane, dichloron-butane ,
Trichloro n-butane, tetrachloro n-butane, monochloroisobutane, dichloroisobutane, trichloroisobutane, tetrachloroisobutane, monofluoromonochloro n-butane, monofluorodichloro n-butane,
Difluoromonochloro n-butane, difluorodichloro n-butane, trifluoromonochloro n-butane, trifluorodichloro n-butane, tetrafluoromonochloro n-butane, tetrafluorodichloro n-butane, monofluoromonochloroisobutane, monofluorodichloroisobutane, Difluoromonochloroisobutane, difluorodichloroisobutane, trifluoromonochloroisobutane, trifluorodichloroisobutane, tetrafluoromonochloroisobutane, tetrafluorodichloroisobutane, monobromomethane, dibromomethane, tribromomethane, tetrabromomethane, monobromoethane, dibromoethane, Examples include tribromoethane, tetrabromoethane, pentabromoethane, monoiodomethane, diiodomethane, etc. It is possible. Particularly preferred halogenated alkanes are trifluoromethane, tetrafluoromethane, difluoroethane, trifluoroethane, tetrafluoroethane and hexafluoroethane. These halogenated alkanes can be used alone or in admixture of two or more.

The alkane, that is, saturated aliphatic hydrocarbon, preferably has 1 to 10 carbon atoms, more preferably 1 to 4 carbon atoms, and examples thereof include methane, ethane, n-propane and n-. Butane, n-pentane, n-hexane, n-heptane, n-octane, n-nonane, n
-Decane and isomers thereof may be mentioned. Particularly preferred alkanes are methane, ethane, propane, n-butane and isobutane. These alkanes can be used alone or in admixture of two or more.

The halogen is fluorine, chlorine, bromine or iodine, with fluorine and chlorine being preferred. These halogens can be used alone or in combination of two or more.

The gas used for plasma polymerization in the present invention comprises any combination of the above (1) to (10). In these combinations, the ratio of the total number of halogen atoms / the total number of hydrogen atoms in the gas is in the range of 0.1 to 5, and the preferable ratio is 0.2 to 3. When the ratio of the total number of halogen atoms / the total number of hydrogen atoms is less than 0.1, the plasma polymerized film has high density and high hardness, but on the contrary, has poor toughness and tends to be damaged. If it exceeds 5, it may be difficult to form a plasma polymerized film. Therefore, for example, when tetrafluoromethane and methane are used as the monomer compounds, it is appropriate that the volume ratio of both is 1:10 to 5: 1 in the standard state, and hexafluoroethane and methane are used. When using and, the volume ratio of both is 3.3: 1 to 1 in the standard state.
A ratio of 1:15 is suitable.

In the formation of the plasma polymerized film in the present invention, when two or more kinds of monomer compounds are used in combination as described in the above (2) to (10), they may be introduced into the plasma polymerization zone as a mixed gas. Alternatively, each monomer compound may be introduced separately and mixed in the plasma polymerization zone.

In the present invention, the electron temperature of the plasma in the plasma polymerization zone is preferably 6,000 to 30,000 °, for example, at a position 1 to 3 cm vertically away from the surface of the lens substrate on which the plasma polymerization film is formed.
K, particularly preferably 10,000 to 28,000 ° K. If the electron temperature is too high, the formed plasma polymerized film will have high density and high hardness, but the adhesiveness to the substrate will tend to decrease, and peeling will tend to occur easily. Moreover, even if the electron temperature of plasma is too low, a plasma polymerized film having irregularities on the surface may be formed. The electron temperature as used herein is measured by a method using a plasma characteristic measuring probe described in JP-A-54-135574, and includes discharge power, discharge current for plasma excitation,
It can be controlled to a desired value by adjusting the pressure of the gas containing the monomer compound, the flow rate of the gas, the structure of the electrode, the position of the substrate, and the like.

Other conditions in the plasma polymerization are essentially the same as those in the ordinary plasma polymerization. For example, the degree of vacuum is about 1 × 10 ^{−3 to} 1 Torr and the flow rate of the gas containing the monomer compound flowing into the reactor. Is about 0.1 to 100 cc (standard state) / minute per 100 liters of the internal volume of the reactor.

When the gas of the above-mentioned monomer compound is introduced into the reactor, an inert gas such as helium, neon, argon or xenon can be used as a carrier gas.

The temperature of the lens substrate during plasma polymerization is not particularly limited as long as the substrate does not deteriorate, and the type of lens substrate, the type of monomer compound, and the above (1) to (1).
According to the combination etc. of 0), it can be appropriately selected from the range of 0 to 300 ° C, for example.

The discharge method and the discharge device used for generating plasma are not particularly limited, and the discharge method is
For example, any of DC discharge, low frequency discharge, high frequency discharge, microwave discharge, etc. may be used, and the discharge device may be any of internal electrode type, external electrode type, electrodeless type, etc. Further, the shapes of electrodes and coils, the structures of cavities and antennas in the case of microwave discharge, etc. can be appropriately selected.

In the present invention, if the thickness of the plasma-polymerized film coating the surface of the lens substrate is too thin, it may be difficult to sufficiently suppress the adhesion of foreign matter on the substrate surface, and it is considerably thick. Also, although there is generally no problem in performance, it is not a good idea from the viewpoint of industrial productivity,
10 to 10 depending on the patient's case, type of monomer compound, etc.
It is selected from the range of 10,000Å. The preferred thickness of the plasma polymerized film is 30 to 3,000Å, more preferably 100 to 3,000Å.

In the present invention, the plasma polymerized film thus formed is substantially composed of carbon (C), hydrogen (H), halogen (X) and oxygen (O) atoms, and The ratio of the number of hydrogen atoms bonded to a carbon atom having a double bond to the number of hydrogen atoms bonded to a carbon atom having only a single bond is 0 to 0.1 while having an average composition of the atomic ratios shown. , Having an essentially amorphous structure.

## STR1 ## The average density of this plasma polymerized film is usually 1.6.
It is about 3.5 g / cm ³ .

From the viewpoint of the adhesion of the plasma polymerized film to the lens substrate, the adhesion of cell components and biological components in the eye, the reduction of adsorption, etc., of the average composition, the atomic number ratio is

[Chemical 4] Is preferred, especially

[Chemical 5] Is preferred.

In the present invention, in plasma polymerization, it is usually not necessary to positively introduce oxygen into the plasma polymerization zone, and oxygen atoms in the plasma polymerization film were covered with the plasma polymerization film from the reactor. It is presumed that when the substrate is taken out, the active radicals remaining in the plasma polymerized film react with oxygen in the atmosphere to be introduced. Further, in the present invention, oxygen may be separately introduced into the plasma polymerization zone in some cases. In the present invention, oxygen present in the plasma polymerized film is considered to result in enhanced biocompatibility.

In the present invention, the ratio of the number of hydrogen atoms bonded to carbon atoms having a double bond to the number of hydrogen atoms bonded to carbon atoms having only a single bond is determined by Fourier transforming the infrared absorption spectrum of the plasma polymerized film. 3010-304 when measured by infrared spectrum (FTIS) method
It is defined as the ratio of the area of the absorption peak at 0 cm ^-1 (corresponding to the CH bond) to the area of the absorption peak at 2840 to 3000 cm ^-1 (corresponding to the -CH bond). The atomic ratio (X / C or O / C) of halogen (X) or oxygen (O) to carbon (C) can be measured, for example, by an X-ray photoelectron spectrum (ESCA) method, and carbon (C The atomic ratio (H / C) of hydrogen (H) to () can be measured using, for example, an elemental analyzer.

The plasma-polymerized film in the present invention contains a large amount of carbon among the elements constituting the plasma-polymerized film.
Characteristic in that hydrogen, halogen and oxygen also coexist,
Further, most of the carbon atoms have only a single bond. Therefore, the plasma polymerized film has extremely high density and high hardness. However, the coexistence of hydrogen, halogen, and oxygen makes the plasma-polymerized film extremely excellent in biocompatibility and has appropriate toughness.

The lens substrate used in the present invention is not particularly limited as long as it is optically transparent and can be adapted to an intraocular lens, and it may be hard or soft. Alternatively, it may be non-hydrated. As such a lens substrate, various materials can be appropriately selected regardless of whether it is plastic, glass or the like. Usually, PMMA resin, acrylic elastomer, silicone resin, silicone elastomer, fluoroalkyl acrylate polymer and the like are used. A copolymer of these constituent monomers such as a special fluorine-based polymer, or a mixture of these polymers with each other is used.

The shape, dimensions, etc. of the intraocular lens coated with the plasma-polymerized film of the present invention are selected according to the case of cataract, etc., but when the intraocular lens is coated with the plasma-polymerized film, the lens forming the optical part is usually used. It is processed in a form in which necessary peripheral members are attached to the base body. As a result, the plasma-polymerized film is coated on both the optical part and the peripheral part, and the entire intraocular lens has sufficient biocompatibility.
Examples of the intraocular lens molded article provided with this peripheral member are shown in FIGS. 1 and 2. Here, 1 is an optical part, and 2 is a peripheral part.

[0028]

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. The thickness of the plasma-polymerized film in each example was ruptured after sufficiently cooling the intraocular lens molded article after the plasma-polymerized film coating treatment in liquid nitrogen, and its cross section was observed with a scanning electron microscope, and measured. . Example 1 An intraocular lens molded product made of PMMA resin in a bell jar type plasma polymerization reactor equipped with an intraocular lens holder (diameter of optical part: 4 mm, total length including peripheral part: 9 mm.
As shown in Table 1, the bellows pressure was 45 mTorr and the discharge current was 140 mA, while flowing a mixed gas of tetrafluoromethane and methane at a flow rate of 8 cc / min (standard state). 0.3
The plasma polymerization film coating treatment (Nos. 1 to 7) was performed while changing the time between ˜19.5 minutes. The thickness of the formed plasma-polymerized film, and the atomic ratio of hydrogen, fluorine or oxygen to carbon, and hydrogen bonded to carbon atoms having a double bond relative to the number of hydrogen atoms bonded to carbon atoms having only a single bond. The ratio of the number of atoms is shown in Table 1.

Example 2 Using the same intraocular lens molding and polymerization reactor as in Example 1, a mixed gas of hexafluoroethane and hydrogen was added,
Flowing at a flow rate of 18 cc / min (standard state) and 6 cc / min (standard state), while the bell jar pressure was 5
At 5 mTorr and a discharge current of 210 mA, the plasma polymerization film coating treatment (No. 8 to 10) was performed while changing the polymerization time between 0.5 to 12.3 minutes as shown in Table 1. The thickness of the formed plasma-polymerized film, and the atomic ratio of hydrogen, fluorine or oxygen to carbon, and hydrogen bonded to carbon atoms having a double bond relative to the number of hydrogen atoms bonded to carbon atoms having only a single bond. The ratio of the number of atoms is shown in Table 1.

Example 3 Using the same intraocular lens molding and polymerization reactor as in Example 1, mixed gas of hexafluoroethane and ethane was mixed at 9 cc / min (standard condition) and 6 cc / min (standard condition), respectively. (State) while flowing at a bell jar pressure of 9
At 5 mTorr and a discharge current of 90 mA, the plasma polymerization film coating treatment (Nos. 11 to 13) was performed by changing the polymerization time between 0.4 and 6.4 minutes as shown in Table 1.
The thickness of the formed plasma-polymerized film, and the atomic ratio of hydrogen, fluorine or oxygen to carbon, and hydrogen bonded to carbon atoms having a double bond relative to the number of hydrogen atoms bonded to carbon atoms having only a single bond. The ratio of the number of atoms is shown in Table 1.

Example 4 Using an intraocular lens molding and a polymerization reactor similar to those in Example 1, difluoroethane gas was flowed at a flow rate of 25 cc / min (standard state), and the pressure inside the bell jar was 50 mT.
The plasma polymerization film coating treatment (Nos. 14 to 16) was carried out at an orr and a discharge current of 45 mA while changing the polymerization time from 0.5 to 7.9 minutes as shown in Table 1. The thickness of the plasma polymerized film formed, and hydrogen to carbon,
Table 1 shows the atomic ratio of fluorine or oxygen and the ratio of the number of hydrogen atoms bonded to carbon atoms having a double bond to the number of hydrogen atoms bonded to carbon atoms having only a single bond.

[0032]

[Table 1]

Test Example The plasma-polymerized film-coated lens 16 of the present invention obtained in each example
Untreated PMMA of the same shape as seed and control
Insert the resin intraocular lens molded product into the eye of each rabbit (Japanese white breed, male, healthy, body weight about 3 kg) from which the lens has been removed by ultrasonic emulsification suction, and photo for 2 months. The tissue reaction and the state of the intraocular lens surface were observed with a slit camera. As a result, unprocessed PM
In rabbits with intraocular lens moldings made of MA resin, fibrin-like substances presumed to be caused by intraocular inflammation were observed within several days after surgery, and iris inflammation was also observed for several weeks after observation. Was done. Untreated PMMA also inserted
In several places around the optical part surface of the resin intraocular lens molded product,
Over a period of 2 months, which was observed from several days after the operation, adherence of extended foreign body giant cells and fibroblast-like cells was observed, and at the same time adsorption of protein-like substances was observed at several places on the surface of the optical part. On the other hand, in all the rabbits into which the 16 types of plasma-polymerized film-coated lenses were inserted, the deposition of fibrin-like substances and the inflammation of the iris were extremely slight as compared with the control. Further, when observed for 2 months after the operation, the experiment No. In 3 cases of 1, 8, and 11, cell adhesion and protein-like substance adsorption were observed at all, except that the adhesion of fibroblast-like cells to the surface of the optical part was very slight to the extent that there was no practical problem. I couldn't do it.

[0034]

The plasma-polymerized film-coated lens of the present invention comprises:
The biocompatibility of the lens substrate surface is extremely high, inflammation after insertion into the eye can be strongly suppressed, and adhesion and adsorption of cell components and biological components can be significantly reduced, resulting in good visual acuity after surgery. Recovery is obtained in a short time. Moreover, since the plasma-polymerized film has appropriate toughness, it can be easily handled before and during surgery.

[Brief description of drawings]

FIG. 1 is a front view of an example of an intraocular lens molded product.

FIG. 2 is a front view of another example of the intraocular lens molded product.

[Explanation of symbols]

 1 Optical part 2 Peripheral part

Claims (1)

[Claims] 1. The surface of a transparent lens substrate is substantially composed of carbon (C), hydrogen (H), halogen (X) and oxygen (O) atoms, and the average of the atomic ratios shown below is used. Coated with a plasma polymerized film having a composition and a ratio of the number of hydrogen atoms bonded to carbon atoms having a double bond to the number of hydrogen atoms bonded to carbon atoms having only a single bond is 0 to 0.1. An intraocular lens characterized by the above. [Chemical 1]