JP3444781B2 - Method for modifying medical polymer and medical polymer substrate - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to the addition of a specific polymer swelling aid (c ) by adding an additive (b) to a polymer substrate (a ) with a supercritical fluid (d ). Agent (b)
The present invention relates to a modified medical polymer base material which does not substantially elute from the polymer base material (a ) to a certain extent below the detection limit in the dissolution test, and a method for modifying the same.

[0002]

2. Description of the Related Art Up to now, attempts have been made to impregnate various additives into a polymer base material which has been applied as a polymer, particularly as a medical device. For example, the predetermined additive can be impregnated by immersing the polymer in a solution containing the specific additive for a long period of time. Furthermore, predetermined additives can be impregnated by dissolving the additives in a supercritical fluid and impregnating the polymer. A typical method is to impregnate a given additive under conditions where the additive is soluble in a supercritical fluid (for example, carbon dioxide gas) and the additive dissolved in the supercritical fluid is compatible with the polymer. is there.

For example, US Pat. No. 4,598,006 describes a method of impregnating a thermoplastic polymer with an impregnating agent (fragrance, insecticide, medicine, etc.) and a supercritical fluid (eg carbon dioxide gas). Is listed. Similarly, US Pat.
No. 20,752 describes a compressed fluid (eg,
It describes a method in which an additive is dissolved in carbon dioxide gas) at a specific concentration, and the solution is brought into contact with the polymer to be dissolved in the polymer to impregnate the additive. The additive used in these has a considerable solubility in the polymer, is a method of impregnating the additive that is impregnated even at a temperature below the critical point, and has a large elution property from the impregnated polymer.

On the other hand, Japanese Patent Publication No. 8-506612 discloses a method of impregnating a polymer base material with an additive which is insoluble in the polymer base material, a carrier liquid (substantially insoluble in the polymer and supercritical fluid) and A method is described in which a mixture of impregnating agents (substantially insoluble in the supercritical fluid) is contacted in a supercritical fluid (eg, carbon dioxide) to confine the impregnating agents in the polymer. According to this method, it becomes possible to impregnate an additive that is substantially insoluble in the polymer, but the additive has a large elution property from the impregnated polymer, and the additive can be easily eluted with a solvent such as water or a buffer solution. To do.

[0005]

DISCLOSURE OF THE INVENTION An object of the present invention is to conduct an elution test with an additive that imparts an excellent function as a medical device.
It is an object of the present invention to provide a polymer base material which does not substantially elute from the polymer base material to a certain extent below the detection limit and has a stable function excellent as a medical device for a long period of time.

[0006]

Means for Solving the Problems The present inventor has conducted extensive studies on a method of impregnating a polymer base material (a) with an additive, and as a result, the polymer base material (a) is soluble in a supercritical fluid. It is an impregnable low-molecular compound and has a solubility of 10% or less in a normal polymer base and is the same as the monomer constituting the polymer substrate , or at least selected from specific compounds.
Also polymeric swelling aid having a chemistry of one similar
By coexisting (c) with the additive (b), it was found that the additive can be substantially contained in the polymer substrate,
The present invention has been completed based on this finding.

That is, the present invention comprises: (1) a polymer base material (a), an additive (b) which is substantially insoluble in the polymer base material, and a polymer base material which is soluble in the supercritical fluid and which can be impregnated. It is a molecular compound that has a solubility of 10% or less in a normal polymer base and is the same as the monomer constituting the polymer substrate , or siloxanyl methacrylic acid.
Silicon-based methacrylic copolymer copolymer with rate as the main component
For the limer base (a), siloxanyl methacrylate,
Chill (meth) acrylate; dimethyl siloxane type
For silicone-based polymer base material (a) whose main component is rigomer
Is a dimethyl silicone type with a molecular weight of about 1000 or less.
Ill; Fluorine-containing acrylate or methacrylate
Fluoro (meth) acrylate polymer group as the main component
Material (a) is siloxanyl (meth) acrylate, fluorine
Containing (meth) acrylates selected from the group consisting of
At least one polymer swelling aid (c) having similar chemical properties is placed in a pressure vessel, and (2) is contacted with a supercritical fluid (d) and is added to the polymer substrate (a). Agent (b) and the polymer swelling aid (c) are impregnated, (3) then supercritical fluid
The polymer swelling aid by circulating (d) in a pressure vessel (c)
And (4) reducing the pressure in the pressure vessel to confine the additive (b) in the polymer base material (a). A method for modifying (a) is provided. It is also characterized in that the polymer substrate (a) is a contact lens material, an intraocular lens material, a spectacle lens material, or a catheter material. It is also characterized in that the additive (b) is a dye, an ultraviolet absorber, an antiglare agent, a photochronic agent, a softening agent, and a hydrophilicity-imparting agent. It is also characterized in that the polymer swelling aid (c) is siloxanyl methacrylate or methyl methacrylate. Further, (1) a polymer base material (a), an additive that is not substantially dissolved in the polymer base material (b), and a low molecular weight compound that is soluble in a supercritical fluid and can be impregnated in the polymer base material The same as the monomer that has a solubility of 10% or less in the agent and that constitutes the polymer base , or siloxanyl methacrylic acid
Silicone-based methacrylic copolymer poly
The polymer base (a) contains siloxanyl methacrylate and methyl
(Meth ) acrylate; dimethylsiloxane-based ori
Silicon-based polymer base material (a) containing gomer as the main component
A dimethyl silicone oil with a molecular weight of about 1000 or less
Mainly fluorine-containing acrylate or methacrylate
Fluoro (meth) acrylate polymer base material
(a) contains siloxanyl (meth) acrylate and fluorine
A few selected from the group consisting of (meth) acrylates
At least one polymer swelling aid (c) having similar chemical properties is placed in a pressure vessel and (2) is contacted with a supercritical fluid (d) and added to the polymer substrate (a). Agent (b) and the polymer swelling aid (c) are impregnated, (3) then supercritical fluid (d)
The polymer swelling aid (c) by flowing out into a pressure vessel to separate out, (4) the pressure in the pressure vessel is reduced to add the additive (b) into the polymer substrate (a). Provided is a polymer base material for medical use, which is obtainable by a method of encapsulation and characterized in that the additive (b) is below a detection limit in a dissolution test. It is also characterized in that the polymer swelling aid (c) is siloxanyl methacrylate or methyl methacrylate.

The present invention will be described in detail below. Polymer substrate provided by (A) a polymer substrate (a) (a) of the present invention include dyes, UV absorbers, antiglare, Hotokuronikku agents, softeners, hydrophilizing agents such additives (b ) Is contained stably over a long period of time,
Additive (b) is soluble under the environment of use such as water and saline
It is characterized by being able to maintain an excellent function with substantially no elution to some extent below the detection limit in the test . The polymer base material (a ) in the present invention is specifically a polymer used for contact lens materials, intraocular lens materials, spectacle lens materials, catheter materials and the like. For example, an acrylic (methacrylic) homopolymer or a copolymer of the monomer and another monomer,
Silicon-based homopolymers or copolymers of the monomers with other monomers, polycarbonate homopolymers or copolymers of the carbonate-based monomers with other monomers, which have been processed into product shapes or Raw materials can be used.

Particularly, the polymer substrate (a ) includes (i)
Widely used in contact lenses and intraocular lenses, selected from siloxanyl (meth) acrylate, fluoroalkyl (meth) acrylate, alkyl (meth) acrylate, and hydrophilic monomers such as (meth) acrylic acid and hydroxyalkyl (meth) acrylate. Polymer and / or crosslinked polymer base material obtained from a component selected from crosslinkable monomers such as ethylene glycol di (meth) acrylate and tetraethylene glycol (meth) acrylate, (ii) polydimethyl silicone dimethacrylate, fluoro-modified A cross-linked polymer base material mainly composed of polydimethyl silicone dimethacrylate and the like, the above hydrophilic monomer and a cross-linkable monomer, (iii) hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxa , Vinylmethylcyclosiloxane, trifluoropropylmethylcyclosiloxane, cyclic siloxane, diphenylsilanediol, hexamethyldisiloxane, tetramethyldisiloxane, divinyltetramethyldisiloxane, etc. iv) Shape memory polymer substrates obtained from styrene, butyl acrylate and crosslinkable monomers are preferred.

(B) Additive (b) 1) The additive (b) in the present invention is a dye, an ultraviolet absorber, an antiglare agent, a photochronic agent, a softening agent, a hydrophilicity imparting agent, etc. It is necessary that it is not eluted from the polymer under the environment, and in the normal state, it does not substantially dissolve in the polymer substrate (a) , or it dissolves only in a very small amount. These additives (b) are appropriately selected according to the physicochemical characteristics of the polymer substrate (a) , anthraquinone dyes, diazo dyes, benzotriazole UV absorbers, benzophenone UV absorbers, Spiropyran-based photoclinic dyes, silicone-based oligomers, hydrophilic silicone-based oligomers, higher fatty acid esters, lipophilic surfactants and the like can be used.

For example, for the purpose of controlling the optical characteristics of the lens by coloring the polymer substrate (a ), Macrolex Blue RR, Violet manufactured by Bayer Co.
3R, Green 5B, Green G, Violet
Anthraquinone dyes such as t B; Macrolex
Pyrazolone dyes such as Yellow 3G; Vioso manufactured by Kyodo Chemical Co., Ltd. for the purpose of controlling the ultraviolet transmittance
rb 550, 580, 582, 583, 590 and 591; Sumitomo Chemical Co., Ltd. Sumisosorb 250; Asahi Denka Kogyo Co., Ltd. ADEKA STAB LA-31 and other benzotriazole ultraviolet absorbers; Asahi Denka Kogyo KK Benzphenone UV absorbers such as ADK STAB LA-51; Silicone oil manufactured by Shin-Etsu Silicon Co., Ltd. for the purpose of improving the mechanical strength of the polymer base (a ); KF355, 615, 353 manufactured by Shin-Etsu Silicon Co., Ltd.
Polyether-modified silicone oils such as 945 and 6004 are preferable, and these are used alone or in combination of two or more kinds.

2) These additives (b) are added to the polymer substrate (a ) in an appropriate amount according to the purpose, but for example, dyes, ultraviolet absorbers, etc. are added in the range of 5 to 5000 ppm. Additives added for the purpose of improving polymer properties such as dynamic strength, flexibility and hydrophilicity are 0.01 to 10
It is added within the range of weight%.

(C) Polymer swelling aid (c) The polymer swelling aid (c) in the present invention is a low molecular weight compound which is soluble in a supercritical fluid and can be impregnated into a polymer substrate in a normal state. It has a solubility of 10% or less and is the same as the monomer that constitutes the polymer substrate , or
Silicon-based meth- ane whose main component is sanyl methacrylate
The acrylic copolymer base (a) contains siloxanylmeth
Acrylate, methyl (meth) acrylate; dimethyl
Silicon-based polymer whose main component is siloxane-based oligomer
The limer base material (a) contains dimethyl having a molecular weight of about 1000 or less.
Silicone oil; Fluorine-containing acrylate or
Fluoro (meth) acrylate containing methacrylate as the main component
The rate polymer substrate (a) contains siloxanyl (meth) actuate.
Group consisting of relate and fluorine-containing (meth) acrylate
Is a compound having at least one similar chemical property selected from These polymer swelling aids (c) are appropriately selected according to the properties of the polymer base material (a) and the additive (b) used. Although the standard cannot be determined unambiguously,
Generally, 1% or more solubility in supercritical fluid (d) in actual use, 10% or less in normal polymer base material (a), and 10% or less even in the coexistence of supercritical fluid (d) Has an additive
It is preferable that the solubility of (b) in the auxiliary agent (c) is 3% or less in the normal state and 3% or less even in the presence of a supercritical fluid.

[0014] is et al., On the use of the resulting polymeric substrate (a) as a medical additive (b) is polymeric substrate (a)
In some cases, it may have a negative effect on the living body by being eluted from the polymer.In order to prevent the additive (b) from being substantially eluted, and in order to prevent the additive (b) from remaining in the polymer substrate (a ), the strength and elastic modulus of the polymer , To prevent deterioration of mechanical properties such as creep deformation and physical properties such as dimensional stability in body fluids, the solubility in the supercritical fluid (d ) in actual use is 1% to 1%.
Within the range of 0%, the solubility in the polymer base material (a ) in the normal state is 5% or less, 10% or less even in the coexistence of the supercritical fluid (d) , and the additive (b) to the auxiliary agent (c ). It is more preferable that the solubility of is 1% or less in the normal state and is 1% or less even in the coexistence of the supercritical fluid (d) .

[0015] As a specific example of that is, the polymer substrate
Among the organic compounds having chemical properties same or similar to the constituent monomers of (a), preferably selected from those easily dissolved in the supercritical fluid. For example, siloxanyl methacrylate and methyl (meth) acrylate are used for the silicone-based methacrylic copolymer having siloxanyl methacrylate as the main component; and molecular weight is used for the silicone-based polymer having dimethylsiloxane oligomer as the main component. Is about 1
A dimethyl silicone-based oil of 000 or less; siloxanyl (meth) acrylate, fluorine-containing (meth) acrylate and the like are preferable for the fluoro (meth) acrylate polymer containing fluorine-containing acrylate or methacrylate as a main component. In particular, (meth) acrylate-based polymer swelling aids include the solubility of the additive (b) , the polymer swelling ability, the affinity balance with the polymer substrate (a ), the additive
When the swelling aid is removed with a supercritical fluid after impregnation with (b), the solubility in the polymer substrate (a ) and the supercritical fluid (d ) is well balanced, and the extraction from the polymer substrate (a ) easy residual to the polymeric substrate (a) is not over substantially the physical properties of the polymeric substrate (a), for example, dimensional stability, because the excellent physical properties such as creep deformation characteristics, more siloxanyl (meth) acrylate preferable.

The swelling aid (c ) according to the present invention is measured for solubility in each medium when the polymer base material (a ), the additive (b) and the supercritical fluid (d ) to be used are determined. hand,
It is selected based on the above criteria. Swelling aid of the present invention (c )
The effect of the additive is not known exactly, but it is more effective than the effect of increasing the solubility of the additive (b) in the supercritical fluid (d ).
(b) in order to assist the diffusion of the polymer substrate (a) shows the effect of increasing the swelling by the supercritical fluid (d) of the polymer substrate (a), the polymer substrate (a) is from itself supercritical fluid It has the property of being easily extracted and removed by (d) . Due to this, the impregnation rate of the additive (b) is high and the polymer substrate
It seems that the impregnation can be performed without changing the properties of (a ).

(D) Supercritical fluid (d) Supercritical fluid (d ) is a fluid maintained above a critical temperature (Tc) and a critical pressure (Pc), and has both gas and liquid properties. It has the property of being easy to diffuse like a gas and shows the solubility of a liquid. The supercritical fluid (d ) that can be used in the present invention is appropriately selected according to the polymer base material (a ), the additive (b) , and the swelling aid (c ), but in general, carbon dioxide gas (Tc = 31.1 ° C, Pc = 7.38 MPa, nitrous oxide (Tc = 36.5 ° C, Pc = 7.26MP)
a), ethane (Tc = 32.3 ° C., Pc = 4.88 MP
A) etc. can be preferably used. In particular, carbon dioxide gas has moderate solubility and swelling property in the supercritical state with respect to the medical polymer base material (a ) and does not deform the shape of the polymer base material.
Moreover, it is highly safe and preferable. The temperature and pressure of the supercritical fluid (d) are determined according to the material used and the purpose. In general, the critical temperature (Tc) and critical pressure (Pc) of the supercritical fluid (d ) used are equal to or higher than the critical temperature (Tc), preferably Tc to Tc + 100.
It is used at a temperature in the range of ° C and a pressure in the range of Pc to Pc + 30 MPa. (E) Other additives and supercritical fluids
As an entrainer for the purpose of controlling the solubility of (d ),
It is also possible to add water, methanol, ethanol, etc. in an amount of several% within a range in which the influence on the polymer substrate (a ) is small.

(F) Manufacture of Medical Polymer Substrate The medical polymer substrate of the present invention comprises a polymer substrate (a ), an additive (b) and a polymer swelling aid (c ) placed in a pressure vessel, impregnated additive to the polymer substrate in contact held in the supercritical fluid (d) (a) and (b) polymeric swelling aid (c), then a supercritical fluid (d) was circulated in the pressure vessel After the polymer swelling aid (c ) is separated by outflow, the pressure in the pressure vessel is reduced and the additive (b) is enclosed in the polymer substrate (a ) to produce the polymer.・ The method of putting the polymer substrate (a ), the additive (b) and the polymer swelling aid (c ) in the pressure vessel includes the shape and thickness of the polymer substrate (a ), the properties of the additive (b) , For example, the target impregnation amount is set depending on the liquid, solid, powder, etc., for example, the powdered additive (b) is sprinkled on the polymer base material (a ) and charged, or the volume of the pressure vessel is reduced. The method of putting in an additive preparation dish having a certain specific surface area is appropriately selected.

The polymer swelling aid (c ) has a low solubility in the polymer in a normal state, so that the polymer swelling aid may be sprinkled on the polymer base material, or may be placed alone in a dedicated dish-shaped container.
It is charged together with an additive or appropriately selected.・ Depending on the post-treatment of the obtained polymer substrate (a ), the impregnated amount of the additive (b) , the concentration distribution, etc., it is 40
It is more preferable to add the additive (b) and the polymer swelling aid (c ) into a container having a specific surface area of ˜200 cm ² / liter, and charge the container separately from the polymer base material (a ).

The time for contacting and holding the supercritical fluid (d ) is
Polymer base material (a ) type, thickness and shape, swelling aid (c ) type, additive (b) type, supercritical fluid (d )
The pressure is appropriately selected according to the pressure and temperature, and the time for impregnation to the center of the base material is set by confirming the impregnation state in the polymer base material (a ). When the impregnation is completed, the polymer substrate (a ) is impregnated with the additive (b) and the polymer swelling aid (c ), and in the present invention, the supercritical fluid (d ) is continuously circulated to polymer the polymer. The swelling aid (c ) is separated by running off. The state of the supercritical fluid (d ) at this time may be the same as or different from the condition at the time of impregnation, but in the case of changing it, it is preferable to set the temperature and pressure to be lower than those at the time of impregnation.・ Since the polymer swelling agent (c ) may remain in the polymer substrate (a ) and affect the physical properties, in order to completely perform the outflow separation, the supercritical fluid (d ) should be circulated in the pressure vessel. polymeric swelling aid was poured off the (c), further the supercritical fluid (d) to the contact holding to the polymeric substrate (a) from the polymer swelling aid (c)
Is preferably extracted and removed.

Further, the medical polymer substrate of the present invention is a polymer substrate impregnated with the additive (b) as described above.
In order to take out (a ), the pressure inside the pressure vessel is reduced from the supercritical state. In this process, in order to maintain the shape of the polymer base material (a ), it is preferable to gently reduce the pressure according to the shape. Usually 5 mm thick
In the polymer product (1), the pressure is preferably reduced at a pressure reduction rate of 0.02 MPa / min or less.

(G) Characteristics of medical-use polymer base material The medical-use polymer base material of the present invention contains various additives (b) useful for medical use when the constituent monomers of the polymer base material (a ) are polymerized. Addition of an additive (b) that changes the properties of the additives under the influence of radicals during polymerization or the heat of polymerization or interferes with the polymerization by affecting the polymerization rate to the polymer base material (a ) without adverse effects. Can be impregnated. Also, in the case of high molecular weight surfactants and modifiers, it is often not possible to add up to the addition amount at which the solubility in the monomer is small and the effect is obtained, but in the method of the present invention, the polymer base material (a ) is impregnated. Therefore, it is possible to impregnate these high molecular weight additives (b) , water from the obtained polymer substrate (a ), physiological saline, tear fluid,
It is possible to provide a highly functional polymer base material (a ) that has virtually no elution of the additive (b) into the liquid that comes into contact with the polymer base material (a ) during actual use, such as body fluid, or even a very small amount. .

[0023]

The present invention will now be described in more detail by way of examples and comparative examples, which do not limit the scope of the present invention. In the examples,% is% by weight. The characteristic evaluation in the examples was carried out by the following methods. (1) Quantitative determination of the impregnated amount of additive Polymer base material impregnated (a ) A polymer material with a thickness of 1 mm is cut out from approximately the center part and immersed in ethanol to elute the additive (b) and the absorbance of the ethanol solution To measure. Further, a calibration curve is prepared from the absorbance of an ethanol solution of additive (b) having a constant concentration to determine the concentration in the sample.
In the case of the additive (b) which does not have a specific absorbance, it is quantified by high performance liquid chromatography using a light scattering detector.

(2) Test for dissolution of additive (b) from polymer substrate (a ) The impregnated polymer substrate (a ) was treated with physiological saline and 10%.
Immerse in physiological saline containing ethanol and leave at 37 ° C. for 24 hours. The absorbance or light scattering of the immersion liquid is measured to determine the additive concentration in the liquid. (3) Dimensional stability of lens A lens is prepared from the impregnated polymer substrate (a ) and immersed in physiological saline, and the radius of curvature of the lens is measured with time. If the radius of curvature changes from the initial value by 3/100 mm or more, it is determined that there is deformation. In addition, 1.2 in the diameter direction of the lens
A load of g is applied and left for 1 week to measure the change in radius of curvature. The creep deformation is large when the change in the radius of curvature is 15/100 mm or more.

Example 1 Twenty-six disc-shaped polymer bases having a diameter of 13 mm and a thickness of 6 mm and made of a polymer of 75% siloxanyl methacrylate, 8% fluoromethacrylate, 9% methacrylic acid, and 8% crosslinking agent were prepared. It was placed in a pressure vessel having an inner diameter of 31 mm and a length of 200 mm, and 1 g of siloxanyl methacrylate in which 930 ppm of Macrolex Violet 3R (Anthraquinone dye manufactured by Bayer Co., Ltd.) was dissolved was placed in a dish-shaped vessel and placed on the top of the pressure vessel. The lid was closed, and the liquefied carbon dioxide gas was heated to 40 ° C. and pressed into the autoclave up to a pressure of 17.5 MPa. After maintaining in this supercritical state for 17 hours, carbon dioxide gas in the same supercritical state was circulated to remove the siloxanyl methacrylate in the container. Furthermore, while maintaining the supercritical state for 17 hours, siloxanyl methacrylate in the polymer substrate was extracted into a supercritical carbon dioxide gas, and the same carbon dioxide in the supercritical state was circulated to remove this. Open the pressure reducing valve of the pressure vessel little by little and set the internal pressure to 0.016 MPa / min.
The pressure was reduced by. After the pressure reached atmospheric pressure, it was released and the polymer substrate was taken out. The polymer substrate is dyed purple
The impregnation amount of Violet 3R was 31 ppm, and the result of the dissolution test was the detection limit of Violet 3R (0.02 p
pm) or less. From this polymer substrate, base curve 7.70mm, power-3.00, size 8.8mm
When the contact lens was manufactured and the dimensional stability was evaluated, the dimensional stability was excellent and there was no deformation and no creep deformation.

Example 2 Twenty-six disc-shaped polymer bases each having a diameter of 13 mm and a thickness of 6 mm and made of a polymer of 75% siloxanyl methacrylate, 8% fluoromethacrylate, 9% methacrylic acid and 8% crosslinking agent were prepared. It was placed in a pressure vessel having an inner diameter of 31 mm and a length of 200 mm, and 930 ppm of Macrolex Violet 3R (Anthraquinone dye manufactured by Bayer Co.) and 4.7% of Smithsorb 250 (benzotriazole ultraviolet absorber manufactured by Sumitomo Chemical Co., Ltd.) were dispersed. 3 g of siloxanyl metaqualate was placed in a dish-shaped container, placed on the upper part of the pressure container, the lid was closed, and liquefied carbon dioxide gas was heated to 50 ° C. to pressurize it to a pressure of 17.5 MPa. After maintaining in this supercritical state for 17 hours, carbon dioxide gas in the same supercritical state was circulated to remove the siloxanyl methacrylate in the container. The temperature of the pressure vessel was set to 40 ° C., the pressure was set to 17.5 MPa, and the state was kept in the supercritical state for another 17 hours to extract siloxanyl methacrylate in the polymer substrate into the supercritical carbon dioxide gas fluid. Carbon dioxide gas was passed through and this was drained off. The pressure reducing valve of the pressure vessel was opened little by little, and the internal pressure was reduced at 0.02 MPa / min. After the pressure reached atmospheric pressure, it was released and the polymer substrate was taken out. The polymer substrate was dyed in purple, the impregnation amount of Violet 3R was 31ppm, and the impregnation amount of the ultraviolet absorber was 1500p.
It was pm. As a result of the dissolution test, each was below the detection limit (Sumisorb 250, 0.04 ppm).
A contact lens having a base curve of 7.70 mm, a power of −3.00, and a size of 8.8 mm was manufactured from this polymer base material, and the dimensional stability was evaluated. As a result, the dimensional stability was excellent and there was no deformation and no creep deformation. . In addition, the lens was excellent in distinguishability, and the ultraviolet cut-off rate at 270 to 310 nm was 96%, which showed excellent performance.

(Comparative Example 1) 26 disk-shaped polymer base materials having a diameter of 13 mm and a thickness of 6 mm and made of a polymer containing 75% of siloxanyl methacrylate, 8% of fluoromethacrylate, 9% of methacrylic acid and 8% of a crosslinking agent, Place in a pressure vessel with an inner diameter of 31 mm and a length of 200 mm, and plate with 0.0093 g of Macrolex Violet 3R (Anthraquinone type dye manufactured by Bayer) and 0.14 g of Smithsorb 250 (benzotriazole type ultraviolet absorber manufactured by Sumitomo Chemical Co., Ltd.). Place it in the container and place it on top of the pressure container.
The mixture was heated to 0 ° C. and press-fitted to a pressure of 17.5 MPa. After maintaining in this supercritical state for 17 hours, carbon dioxide gas in the same supercritical state was circulated. Pressure vessel temperature is 40 ℃, pressure is 1
The mixture was kept at 7.5 MPa for 17 hours and kept in a supercritical state to extract siloxanyl methacrylate (residual monomer) in the polymer base material into a supercritical carbon dioxide gas fluid, and the same supercritical carbon dioxide gas was circulated. It was washed away. Open the pressure reducing valve of the pressure vessel little by little and set the internal pressure to 0.02 MPa /
The pressure was reduced at min. After the pressure reached atmospheric pressure, it was released and the polymer substrate was taken out. The polymer substrate was dyed a light purple color, and the impregnation amount of Violet 3R was 10 ppm,
The impregnated amount of the ultraviolet absorber was 400 ppm. The dissolution tests were all below the detection limit. A contact lens was made from this polymer base material, but the color was thin and the discrimination was poor, and the UV cut rate was 50 at 270 to 310 nm.
It was inferior only by%.

Example 3 A polymer substrate was treated by the same method as in Example 2 except that methylmethacrylate was used as a polymer swelling aid instead of siloxanylmethacrylate. Violes in the obtained polymer substrate
The impregnated amount of t 3R was 43 ppm, which showed a deep purple color, and the impregnated amount of the ultraviolet absorber was 1800 ppm. The dissolution test was also below the detection limit. A contact lens was similarly prepared from this polymer base material, and the dimensional stability was evaluated. As a result, the base curve changed by about 18/100 after 3 months. Further, the creep deformation was 15/100, which was slightly deformable.

Example 4 Diameter 13 composed of a polymer of 55% siloxanyl methacrylate, 10% methyl methacrylate, 18% fluoromethacrylate, 9% methacrylic acid and 8% crosslinking agent.
26 disc-shaped polymer base materials with a thickness of 6 mm and an inner diameter of 3
Put in a pressure vessel with a length of 1 mm and a length of 200 mm, and add 1 g of methylphenyl silicone oil (Shin-Etsu Silicone HIV
AC F-5) and 2 g of siloxanyl methacrylate were placed in a dish-shaped container and placed on the upper part of the pressure container, the lid was closed and liquefied carbon dioxide gas was heated to 40 ° C. and pressure-inserted to 17.5 MPa. After holding in this supercritical state for 17 hours,
The same supercritical carbon dioxide gas was circulated to remove the siloxanyl methacrylate in the container. Further, while maintaining the supercritical state for 17 hours, siloxanyl methacrylate in the polymer substrate was extracted into a supercritical carbon dioxide gas, and the same carbon dioxide in the supercritical state was circulated to remove this. Open the pressure reducing valve of the pressure vessel little by little and set the internal pressure to 0.016 MPa / m.
The pressure was reduced in. After the pressure reached atmospheric pressure, it was released and the polymer substrate was taken out. The polymer substrate was transparent, the impregnation amount of silicone oil was about 210 ppm, and the elution property was below the detection limit (0.5 ppm). A contact lens having a base curve of 7.70 mm, a power of −3.00, and a size of 8.8 mm was manufactured from this polymer base material, and the dimensional stability was evaluated. As a result, the dimensional stability was excellent and there was no deformation and no creep deformation. . The impact resistance was evaluated by a falling ball impact test, and as a result, the impact resistance was about twice as high as that of a lens made of an unimpregnated polymer base material.

Example 5 Diameter 1 composed of a polymer of 55% siloxanyl methacrylate, 10% methyl methacrylate, 18% fluoromethacrylate, 9% methacrylic acid and 8% crosslinking agent.
Twenty-six disc-shaped polymer base materials having a thickness of 3 mm and a thickness of 6 mm were placed in a pressure vessel having an inner diameter of 31 mm and a length of 200 mm, and a hydrophilic modified silicone (modified silicone K manufactured by Shin-Etsu Silicone Co., Ltd.
F355A) 1 g and siloxanyl methacrylate 2 g
Was placed in a dish-shaped container, placed on the upper part of the pressure container, the lid was closed, and liquefied carbon dioxide gas was heated to 40 ° C. to pressurize it to a pressure of 17.5 MPa. After maintaining in this supercritical state for 17 hours, carbon dioxide gas in the same supercritical state was circulated to remove the siloxanyl methacrylate in the container. Further, while maintaining the supercritical state for 17 hours, siloxanyl methacrylate in the polymer substrate was extracted into a supercritical carbon dioxide gas, and the same carbon dioxide in the supercritical state was circulated to remove this. Open the pressure reducing valve of the pressure vessel little by little and set the internal pressure to 0.016MP
The pressure was reduced at a / min. After the pressure reached atmospheric pressure, it was released and the polymer substrate was taken out. The polymer substrate was transparent and the impregnation amount of hydrophilic silicone oil was about 360 ppm. The dissolution test was below the detection limit (o.3ppm). Base curve 7.7 from this polymer substrate
When a contact lens having a size of 0 mm, a power of −3.00, and a size of 8.8 mm was manufactured and the dimensional stability was evaluated, the dimensional stability was excellent and there was no deformation and no creep deformation.
In addition, as a result of evaluating impact resistance by a falling ball impact test, it showed an impact resistance strength about 2.5 times that of a lens made of an unimpregnated polymer base material. Further, the lens surface was excellent in water wettability, and the time from the immersion of the lens in physiological saline to the pulling up until the drainage started was long and the wettability was maintained for 2 minutes or more.

(Example 6) Styrene 45%, butyl acrylate 55%, 2,2-
Glass transition point 2 consisting of 20% of bis [4- (methacryloyl poly (oxyethylene) oxyphenyl] propane]
Put a polymer base material for a 0 ° C non-hydrate fodable intraocular lens in a pressure vessel, and disperse 3% of styrene in which 4.7% of Sumisorb 250 (benzotriazole type ultraviolet absorber manufactured by Sumitomo Chemical Co., Ltd.) was dispersed. Put it in a container and install it at the top and bottom of the pressure container, close the lid and let the liquefied carbon dioxide gas reach
The mixture was heated to a pressure of 17.5 MPa. After maintaining in this supercritical state for 17 hours, carbon dioxide gas in the same supercritical state was circulated to remove the siloxanyl methacrylate in the container. Pressure vessel temperature is 40 ° C, pressure is 17.5M
While maintaining Pa in the supercritical state for another 17 hours, styrene in the polymer substrate is extracted into the supercritical carbon dioxide fluid,
The same carbon dioxide in the supercritical state was circulated and the carbon dioxide was discharged.
Open the pressure reducing valve of the pressure vessel little by little and set the internal pressure to 0.02.
The pressure was reduced at MPa / min. After the pressure reached atmospheric pressure, it was released and the polymer substrate was taken out. The impregnated amount of the ultraviolet absorber in the polymer substrate was 2300 ppm. The result of the dissolution test was below the detection limit (0.04 ppm). When an intraocular lens was manufactured from this polymer base material and dimensional stability was evaluated, it was excellent in dimensional stability, and there was no deformation and no creep deformation. Also, 270 to 310
The UV cut-off ratio in nm was 97%, indicating excellent performance. The results of the additive dissolution test were below the detection limit.

[0032]

INDUSTRIAL APPLICABILITY The present invention provides a highly functional polymer base material useful for medical instruments and tools. Furthermore, according to the method of the present invention, it is possible to impregnate the high molecular weight additive (b) ,
There is substantially no elution of the additive (b) from the resulting polymer base material (a ) into a liquid such as water, physiological saline solution, tear fluid, or body fluid that comes into contact with the polymer base material (a) during actual use, or Even if it exists, the amount is extremely small (that is, below the detection limit in the dissolution test).
It is possible to provide a high-performance polymer base material (a ) ( below ).

Claims (6)

(57) [Claims] 1. A polymer base material (a), an additive (b) which is substantially insoluble in the polymer base material, and a low-molecular compound which is soluble in a supercritical fluid and can be impregnated into the polymer base material, in a normal state. It has a solubility of 10% or less in the polymer base and is the same as the monomer constituting the polymer base , or siloxanil
Silicon-based methacrylic with taacrylate as the main component
The copolymer polymer substrate (a) contains siloxanyl methacrylic acid.
, Methyl (meth) acrylate; dimethylsiloxa
Silicon-based polymer group mainly composed of vinyl-based oligomers
The material (a) is dimethyl silicone having a molecular weight of about 1000 or less.
Oils; fluorine-containing acrylate or methacrylic acid
Fluoro (meth) acrylate containing mainly rate
Siloxanyl (meth) acrylate for the limer base (a)
And fluorine-containing (meth) acrylate
At least one selected polymer swelling aid having similar chemical properties (c) is placed in a pressure vessel, and (2) is brought into contact with the supercritical fluid (d) to be retained on the polymer substrate (a). The additive
(b) and the polymer swelling aid (c) are impregnated, (3) then the supercritical fluid (d) is circulated in the pressure vessel to separate the polymer swelling aid (c) by outflow separation, and then (4) ) A method for modifying a polymer substrate with an additive, characterized in that the pressure in a pressure vessel is reduced and the additive (b) is enclosed in the polymer substrate (a). 2. The polymer base material is modified with the additive according to claim 1, wherein the polymer base material (a) is a contact lens material, an intraocular lens material, a spectacle lens material, or a catheter material. how to. 3. The additive according to claim 1 or 2, wherein the additive (b) is a dye, an ultraviolet absorber, an antiglare agent, a photochronic agent, a softening agent, or a hydrophilicity-imparting agent. A method of modifying a polymer substrate by means of. 4. The method for modifying a polymer base material according to claim 1, wherein the polymer swelling aid (c) is siloxanyl methacrylate or methyl methacrylate. 5. A polymer base material (a), an additive (b) which is substantially insoluble in the polymer base material, and a low-molecular compound which is soluble in the supercritical fluid and can be impregnated into the polymer base material in a normal state. It has a solubility of 10% or less in the polymer base and is the same as the monomer constituting the polymer base , or siloxanil
Silicon-based methacrylic with taacrylate as the main component
The copolymer polymer substrate (a) contains siloxanyl methacrylic acid.
, Methyl (meth) acrylate; dimethylsiloxa
Silicon-based polymer group mainly composed of vinyl-based oligomers
The material (a) is dimethyl silicone having a molecular weight of about 1000 or less.
Oils; fluorine-containing acrylate or methacrylic acid
Fluoro (meth) acrylate containing mainly rate
Siloxanyl (meth) acrylate for the limer base (a)
And fluorine-containing (meth) acrylate
At least one selected polymer swelling aid having similar chemical properties (c) is placed in a pressure vessel, and (2) is brought into contact with the supercritical fluid (d) to be retained on the polymer substrate (a). The additive
(b) and the polymer swelling aid (c) are impregnated, (3) then the supercritical fluid (d) is circulated in the pressure vessel to separate the polymer swelling aid (c) by outflow separation, and then (4) ) The additive (b) can be obtained by a method in which the pressure in the pressure vessel is reduced to confine the additive (b) in the polymer substrate (a), and the additive (b) is below the detection limit in the dissolution test. A medical polymer base material characterized by: 6. The medical polymer base material according to claim 5, wherein the polymer swelling aid (c) is siloxanyl methacrylate or methyl methacrylate.