JP7110973B2 - Medical device substrate, medical device laminate, and method for producing medical device substrate - Google Patents

Description

TECHNICAL FIELD The present invention relates to a medical device substrate that exhibits low cytotoxicity and an excellent effect of suppressing adsorption of proteins and reagents, a medical device laminate, and a method for producing a medical device substrate.

Silicone materials are excellent in heat resistance, cold resistance, hardness, physical strength, durability, and safety, so they are used in a wide range of applications including medical materials. Attempts to observe or measure chemical reactions of cells held on a substrate such as glass are expected to bring advantages such as simplification of operation and shortening of analysis time through automation, and have been actively carried out in recent years. Advantages of a system using a microchip include that the amount of samples and reagents used and the amount of waste liquid discharged are reduced, and that the system is space-saving, portable, and inexpensive.
For example, in Non-Patent Document 1, taking advantage of the above advantages, research is also being conducted to evaluate the functions and responses of cells using a microchip in which cells are adhered to the walls of a channel made of silicone.
However, in Non-Patent Document 2, in a microchip using cells, the silicone surface of the device is adsorbed by proteins derived from biological samples, or by radioactively labeled compounds such as dexamethasone used in residue tests, causing clogging and analysis. The problem was that it caused a decrease in accuracy and sensitivity.
In order to solve this problem, for example, Patent Document 1 discloses a microfluidic device coated with an anti-adhesion agent containing, as an active ingredient, a polymer having a hydrophilic structure such as polyethylene glycol and/or a betaine structure. It has been reported. However, there is a large difference in surface tension between the anti-adhesion agent and the wall surface of the channel wall of the silicone substrate. There was concern about layer durability.

WO2017/022815

Analytical Chemistry 2005:77, p. 2125-2131 TECHNOLOGY VOLUME5. NUMBER1. March 2017

An object of the present invention is to provide a medical device base material, a medical device laminate, and a method for producing a medical device base material, which are improved in the effect of suppressing adsorption of proteins and reagents.

The present invention provides a medical device base material comprising a reactive silicone oil (A) and a polydimethylsiloxane resin (B) (excluding the case where the reactive silicone oil (A) is used),
The viscosity of the reactive silicone oil (A) at 25° C. according to JISZ 8803 is 1 to 17,000 [mm ² /s],
The reactive silicone oil (A) is 0.10 to 50% by mass and the polydimethylsiloxane resin (B) is 50 to 99.9% by mass with respect to the entire base material for medical devices. It relates to a base material for medical devices.

Further, in the present invention, the reactive silicone oil (A) is one or more selected from acryloyl group-modified silicone oil (A1), epoxy group-modified silicone oil (A2), and diol group-modified silicone oil (A3). The present invention relates to the above base material for medical devices.

Further, in the present invention, the reactive silicone oil (A) is
terminal (meth)acryloyl group-modified silicone oil (A1) having a functional group equivalent of 100 to 12,000 g/mol;
A side chain or single end epoxy group-modified silicone oil (A2) having a functional group equivalent weight of 250 to 5,000 g/mol, and
The base material for medical devices is at least one selected from one-end diol group-modified silicone oils (A3) having a functional group equivalent weight of 1 to 1,000 g/mol.

The present invention also relates to a medical device laminate, which is obtained by laminating the medical device substrate and the coating layer (Y).

In the present invention, the oxygen permeability coefficient (Dk) of the medical device laminate according to ISO18369-4 (FATT method) is 280 Barrer (1 Barrer=1×10 ⁻¹¹ O ₂ (STP) cm/cm ² mmHg) or more. It is related with the said medical device laminated body.

The present invention also provides a method for producing a base material for medical devices containing a reactive silicone oil (A) and a polydimethylsiloxane resin (B),
Alkenyl group-containing polyorganosiloxane and SiH group-containing organohydrogenpolysiloxane are reacted to form a polydimethylsiloxane resin (B), and then mixed with a reactive silicone oil (A). It relates to the manufacturing method of wood.

By using the medical device base material and the medical device laminate of the present invention, the affinity between the coating agent for suppressing protein adsorption and the silicone base material such as a microfluidic device is improved. As a result, the durability of the coating layer was improved.

<Reactive silicone oil (A)>
The reactive silicone oil is a linear or cyclic silicone having a siloxane bond in its main chain and exhibits fluidity at room temperature, and may have other bonds in its main chain.
The reactive silicone oil (A) has a structure represented by general formula 1 with a bifunctional siloxane (D unit) as a main skeleton.

Each R is independently a methyl group, a phenyl group, or a reactive substituent, at least one of which is a reactive substituent.
n is an integer of 1 or more.

Specific examples of reactive substituents include substituents containing amino groups, epoxy groups, carboxyl groups, (meth)acryloyl groups, hydroxy groups, and the like.
One substituent may have two or more reactive substituents at the same time. Also, two substituents that bond to the same silicon element may each be a reactive substituent. As such an example, a diol group-modified one in which two hydroxyalkyl groups are bonded to the same silicon element is preferable. Among these, (meth)acryloyl group-modified silicone oil (A1), epoxy group-modified silicone oil (A2), and diol group-modified silicone oil (A3) are preferable. It is more preferred to have oil (A3).
In addition, the reactive substituent may be directly bonded to the silicon element of the main chain, may be bonded to a side chain possessed by the silicon element of the main chain, or may be present at one end or both ends of the main chain. may be Among these, from the viewpoint of compatibility with the following polydimethylsiloxane resin (B), terminal (meth)acryloyl group-modified silicone oil (A1), side chain or one terminal epoxy group-modified silicone oil (A2), one terminal A diol group-modified silicone oil (A3) is preferably used.

[Functional group equivalent]
The terminal (meth)acryloyl group-modified silicone oil (A1) preferably has a functional group equivalent weight of 100 to 12,000 g/mol. If the functional group equivalent weight is less than 100 g/mol, segregation of the acryloyl group on the surface of the base material for medical devices described below does not easily occur, and the hydrophilization and modification effect on the surface of the base material is not remarkable, and the following protein adsorption occurs. It is expected that the suppressive coating will have poor adhesion to the substrate. On the other hand, if the functional group equivalent exceeds 12,0000 g/mol, the compatibility with the polydimethylsiloxane resin (B) described below is reduced, and it becomes difficult to uniformly blend a large amount of the polydimethylsiloxane resin (B). can be.
Further, the functional group equivalent weight of the side chain/single terminal epoxy group-modified silicone oil (A2) is preferably 250 to 5,000 g/mol. Further, the functional group equivalent of the one-terminal diol group-modified silicone oil (A3) is preferably 1 to 1,000 g/mol.
The reason is the same as the terminal (meth)acryloyl group-modified silicone oil (A1).

[viscosity]
The viscosity of the reactive silicone oil (A) at 25° C. is 1 to 17,000 [mm ² /s]. 1 to 2,000 [mm ² /s] is preferable. If this viscosity is less than 1 [mm ² /s], the viscosity is too low to be sufficient for mixing with the polydimethylsiloxane resin (B) described below, while if it exceeds 17,000 [mm ² /s] However, the moldability of the following base material for medical devices is lowered, which is not preferable.
The viscosity of the reactive silicone oil (A) was measured using a capillary viscometer in accordance with the viscosity at 25° C. (JISZ8803 (2011)).

As a commercial product of the terminal (meth)acryloyl group-modified silicone oil (A1) of the present invention, X-22-174BX manufactured by Shin-Etsu Chemical Co., Ltd. (one terminal modified, viscosity: 27 [mm ² / s], functional group equivalent: 2300 g / mol), X-22-174ASX (single end modified, viscosity: 9 [mm ² /s], functional group equivalent: 900 g/mol), KF-2012 (single end modified, viscosity: 60 [mm ² /s], functional group equivalent: 4600 g/mol), X-22-2426 (single end modified, viscosity: 200 [mm ² /s], functional group equivalent: 12,000 g/mol), X-22-2404 (single end modified, viscosity: 5 [mm ² /s], functional group equivalent: 420 g/mol).
As a commercial product of the side chain or one end epoxy group modified silicone oil (A2) of the present invention, X-22-173BX manufactured by Shin-Etsu Chemical Co., Ltd. (single end modified, viscosity: 30 [mm ² /s], functional group equivalent: 2500 g /mol), KF-1001 (side chain modification, viscosity: 17,000 [mm ² /s], functional group equivalent: 3500 g/mol).
Commercially available products of the one-end diol group-modified silicone oil (A3) of the present invention include X-22-176DX (viscosity: 130 [mm ² /s], functional group equivalent: 35 g/mol) manufactured by Shin-Etsu Chemical Co., Ltd., X-22 -176F (viscosity: 500 [mm ² /s], functional group equivalent: 9 g/mol), X-22-176GX-A (viscosity: 400 [mm ² /s], functional group equivalent: 8 g/mol), etc. can be mentioned.

<Polydimethylsiloxane resin (B)>
The polydimethylsiloxane resin (B) of the present invention has a siloxane skeleton, but has a viscosity of more than 17,000 and is excluded if it is a reactive silicone oil (A). Polydimethylsiloxane resin (B) is preferably obtained by cross-linking a precursor containing alkenyl group-containing polyorganosiloxane with a cross-linking agent containing SiH group-containing organohydrogenpolysiloxane. In the following, the alkenyl group-containing polyorganosiloxane is also referred to as "polysiloxane (b1)" and the organohydrogenpolysiloxane is also referred to as "polysiloxane (b2)".

A known method can be applied to the cross-linking reaction between the “polysiloxane (b1)” and the “polysiloxane (b2)”.

The polydimethylsiloxane resin (B) may be linear, branched, or cyclic. Moreover, these may be used individually by 1 type, and may be used in combination of 2 or more type.

The ratio of polysiloxane (b1) and polysiloxane (b2) used in producing the polydimethylsiloxane resin (B) is not particularly limited.

[Polysiloxane (b1)]
The polysiloxane (b1), which is a precursor of the polydimethylsiloxane resin (B), means polysiloxane having alkenyl groups bonded to silicon atoms. The alkenyl group content is not particularly limited. Alkenyl groups include, for example, vinyl groups, allyl groups, propenyl groups, methallyl groups, butenyl groups, and hexenyl groups. Of these, a vinyl group is preferred.

The polysiloxane (b1) may have a substituent (organo group) other than the alkenyl group, such as a substituted or unsubstituted alkyl group having 1 to 8 carbon atoms, a substituted or unsubstituted an alkoxy group having 1 to 8 carbon atoms, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group, and the like. Examples of alkyl groups having 1 to 8 carbon atoms include, specifically, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl groups such as hexyl and octyl groups. Among these, a methyl group is preferred.

Alkoxy groups having 1 to 8 carbon atoms include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, hexyloxy and An octyloxy group and the like can be mentioned. Aryl groups include a phenyl group, a methylphenyl group, and the like. Aralkyl groups include benzyl, phenethyl and diphenylmethyl groups.
Examples of groups that can be substituted with the alkenyl group, alkyl group, alkoxy group, aryl group, or aralkyl group include halogen atoms, acyl groups, alkyl groups, phenyl groups, alkoxyl groups, amino groups, alkylamino groups, A carbonyl group, a cyano group, and the like.

[Polysiloxane (b2)]
Polysiloxane (b2) (organohydrogenpolysiloxane), which is a cross-linking agent for polysiloxane (b1), is a polysiloxane having at least two silicon-bonded hydrogen atoms. The two hydrogen atoms are added to the double bond of the alkenyl group of the polyorganosiloxane to form a crosslinked structure.

In addition, the polysiloxane (b2) may have a substituent (organo group) other than the hydrogen atom, and examples of the substituent include those exemplified for the above polysiloxane. The silicone rubber may be linear, branched, or cyclic. Moreover, these may be used individually by 1 type, and may be used in combination of 2 or more type.

[catalyst]
The polydimethylsiloxane resin (B) of the present embodiment may further contain a catalyst for cross-linking the precursor polysiloxane (b1) and polysiloxane (b2). The catalyst is not particularly limited, but is preferably a platinum-based catalyst. Specifically, platinum black, silica-supported platinum, carbon-supported platinum, chloroplatinic acid, chloroplatinic acid alcohol solution, platinum/olefin complex, platinum /alkenylsiloxane complexes, platinum/β-diketone complexes, platinum/phosphine complexes, and the like. The catalyst is preferably added in an amount of about 0.1 to 500 ppm (in terms of Pt) with respect to the total amount of polysiloxane (b1).
Commercial products of the polydimethylsiloxane resin (B) of the present invention include Sylard 184 main agent or Sylard 186 main agent, which is a two-component curable polydimethylsiloxane (PDMS) manufactured by Dow Corning Toray Co., Ltd., and Sylard 184 curing agent or and Sylard 186 curing agent at a mass ratio of 10:1.

<Base material for medical devices>
The base material for medical devices of the present invention is characterized by containing the reactive silicone oil (A) and the polydimethylsiloxane resin (B). The medical device substrate contains 0.10 to 50% by mass, more preferably 1 to 40% by mass, of the reactive silicone oil (A). The content of the polydimethylsiloxane resin (B) is preferably 1 to 99.90% by mass, more preferably 50 to 99% by mass.

By setting the content of the reactive silicone oil (A) to 0.10% by mass or more, the effect of hydrophilization of the base material by the reactive functional group can be exhibited, and the protein of the following medical device laminate, etc. of adsorption can be ensured. Moreover, by setting the content of the polydimethylsiloxane resin (B) to 1% by mass or more, the moldability of the base material for medical devices can be ensured.
For the base material for medical devices, for example, an alkenyl group-containing polyorganosiloxane and a SiH group-containing organohydrogenpolysiloxane are reacted to form a polydimethylsiloxane resin (B), and then a reactive silicone oil (A) can be mixed. can get.

The base material for medical devices of the present invention can be used by laminating and molding a mixture of a reactive silicone oil (A) and a polydimethylsiloxane resin (B) on glass, metal, plastic, release paper, or the like. However, after lamination, it can be peeled off from the release paper and used alone as a substrate.
As a method for molding the base material for medical devices of the present invention, it can be molded into a required shape by various molding methods such as mold pressure molding and injection molding. Also, the molding temperature and molding time are not particularly limited, but molding at room temperature to 160° C. is generally preferred.

The base material for a medical device of the present invention contains the reactive silicone oil (A), the polydimethylsiloxane resin (B), and, if necessary, an inorganic filler, other additives, etc., using a known mixing and stirring device. can be mixed and included.

[Inorganic filler]
Furthermore, the base material for medical devices of the present invention may contain an inorganic filler for adjusting hardness, improving heat resistance, and as a bulking agent. There are various inorganic fillers commonly used in silicone elastomers, including fumed silica, precipitated silica, or surface-treated finely divided silica, powders of diatomaceous earth, quartz, clay, and the like.
Commercially available inorganic fillers include fumed silica having a BET specific surface area of 200 m ² /g (product name “Aerosil 200”, manufactured by Nippon Aerosil Co., Ltd.).

[Other additives]
The base material for medical devices of the present invention may contain carbon black such as acetylene black, furnace black, channel black, etc., as long as it does not contradict the purpose. If necessary, additives such as pigments (colorants such as red iron oxide and various organic pigments, titanium dioxide, heat-resistant agents, flame retardants, internal release agents, plasticizers, and non-functional silicone oils may be added.
Examples of internal release agents include higher fatty acid salts such as calcium stearate. When the microchip for cell culture is to be used for heat sterilization, treatment exposed to high temperatures such as the use of a thermocouple, it is particularly preferable to add a heat-resistant agent, a flame retardant, and the like.

<Coating agent (C)><Coating layer (Y)><Medical device laminate>
The coating agent (C) of the present invention is laminated as a coating layer (Y) on a base material for medical devices, and exhibits low cytotoxicity, an effect of suppressing adsorption of proteins and reagents, an oxygen permeability, an effect of promoting spheroid formation, and the like. Used to give functionality. There are no particular restrictions as long as it is possible to impart functions.

The method for laminating the coating layer (Y) of the present invention is carried out by applying the solution to the base material by various coating methods such as brush, dipping, roller, spraying, injection, and a coater, followed by drying. On the other hand, when the substrate is in the form of a film, dip coating, comma coating, gravure coating, curtain coating, die coating, lip coating, micro gravure coating, slot die coating, reverse coating, kiss coating and the like can be used. Although the film thickness of the coating film after removing the solvent after coating is not limited, it is preferably 1 mm or less.

The coating agent (C) of the present invention comprises, for example, a coating agent resin (C1). It can be prepared by homogeneously mixing according to methods well known in the art.
For example, Lipdure [LIPIDURE-PMB] (C1-1) manufactured by NOF Corporation, methoxyethyl acrylate and acrylic acid described in Production Example 1 of JP 2016-112397 and VPE0201 (Wako Pure Chemical Industries, Ltd.) Co., Ltd.) coating agent resin (C1-2), N-methacryloyloxyethyl-N,N-dimethylammonium-α-N manufactured by Osaka Organic Chemical Industry Co., Ltd. described in Synthesis Example 9 of International Publication WO2017-022815 -Coating agent resin (C1-3) of methyl carboxy betaine and lauroxy polyethylene glycol (30) monomethacrylate (PL-1300) manufactured by NOF Corporation.

[Curing agent (C2)]
In addition, the coating agent (C) of the present invention can further contain a curing agent. By including a curing agent, when the coating agent resin (C1) has a crosslinkable group (for example, the coating agent resin (C1-2)), the coating layer (Y) is crosslinked to provide durability (water resistance). can be improved.

The crosslinkable group possessed by the coating agent resin (C1-2) described above preferably reacts with at least one crosslinkable group selected from the group consisting of a carboxyl group and a hydroxyl group. Examples of cross-linking agents for cross-linkable groups include isocyanate compounds, aziridine compounds, carbodiimide compounds, amino compounds, and the like, as cross-linking agents for block copolymers into which carboxyl groups have been introduced. Examples of cross-linking agents for block copolymers into which hydroxyl groups have been introduced include carbodiimide compounds, isocyanate compounds, amino compounds, and alkoxysilane compounds. These curing agents (C2) can be used for the purpose of increasing the elastic modulus and durability of the coating layer (Y), and can be used for adjusting the adhesion to the substrate.

Carbodiimide compounds are described below as preferred examples of the curing agent (C2).
[Carbodiimide group-containing compound (carbodiimide compound)]
Examples of carbodiimide group-containing compounds include dicarbodiimides such as N,N'-diisopropylcarbodiimide, N,N'-dicyclohexylcarbodiimide, N,N'-di-2,6-diisopropylphenylcarbodiimide, poly(1,6-hexa methylenecarbodiimide), poly(4,4'-methylenebiscyclohexylcarbodiimide), poly(1,3-cyclohexylenecarbodiimide), poly(1,4-cyclohexylenecarbodiimide), poly(4,4'-dicyclohexylmethanecarbodiimide) , poly(4,4′-diphenylmethanecarbodiimide), poly(3,3′-dimethyl-4,4′-diphenylmethanecarbodiimide), poly(naphthalenecarbodiimide), poly(p-phenylenecarbodiimide), poly(m-phenylenecarbodiimide) ), poly(tolylcarbodiimide), poly(diisopropylcarbodiimide), poly(methyl-diisopropylphenylenecarbodiimide), poly(1,3,5-triisopropylbenzene) polycarbodiimide, poly(1,3,5-triisopropylbenzene) Polycarbodiimides such as polycarbodiimide, poly(1,5-diisopropylbenzene)polycarbodiimide, poly(triethylphenylenecarbodiimide), poly(triisopropylphenylenecarbodiimide) and the like can be mentioned.

In the present invention, the curing agent (C2) may be used singly or in combination. The amount of the curing agent (C2) to be used may be determined in consideration of the types and number of moles of functional groups contained in the coating agent (C1), and is not particularly limited. By blending in a range less than the number of moles of the functional groups contained in, it is possible to eliminate the concern that the unreacted curing agent (C2) will be liberated.

The coating agent (C) of the present invention preferably contains 50% by mass or less, more preferably 0.5 to 10% by mass, of the coating agent resin (C1) based on 100% by mass of the coating agent (C). By setting the content of the coating agent resin (C1) to 0.5% by mass or more, it is possible to exhibit adsorption of proteins and the like. Moreover, the coating agent (C) of the present invention may contain components other than the coating agent resin (C1) and the curing agent (C2).

[solvent]
The coating agent (C) of the present invention may contain a solvent as a component other than the coating agent resin (C1) and the curing agent (C2), or may contain two or more of them in combination. The solvent can be appropriately selected from conventionally known solvents in consideration of, for example, the solubility of the block copolymer, which depends on the amount of amine oxide, the film-forming conditions, and the like, depending on the application.

For example, water, alcohols such as methanol and ethanol, ketones such as acetone and ethyl methyl ketone, ethers such as tetrahydrofuran and diethyl ether, esters such as methyl acetate and ethyl acetate, dimethyl sulfoxide, acetonitrile, formic acid and acetic acid, etc. organic acids, organic bases such as N,N-dimethylformamide, or ketones such as acetone and ethyl methyl ketone, ethers such as tetrahydrofuran and diethyl ether, esters such as methyl acetate and ethyl acetate, dimethyl sulfoxide, and acetonitrile. In addition, halogen solvents such as dichloromethane and trichloromethane can be selected.

[Other additives, etc.]
The coating agent (C) of the present invention may contain various additives within a range that does not impair the effects of the present invention, such as surfactants, tonicity agents, chelating agents, pH adjusters and buffers. , thickeners, stabilizers, proteolytic enzymes, pharmacologically active ingredients, bioactive ingredients, and various additives described in the Dictionary of Pharmaceutical Additives, etc., as long as the effects of the present invention are not impaired. . These may contain 1 type independently and may contain 2 or more types.
For example, it may contain a pH adjuster to adjust the ion balance. pH adjusters include acidic or basic compounds. Examples of acidic pH modifiers include carboxylic acids, inorganic acids and sulfonic acids, and examples of basic pH modifiers include nitrogen-containing compounds other than hydroxides, alkoxides, primary and secondary amines. , basic carbonates, and basic phosphates. The pH value of the cell cultureware treatment agent is about 4.0 to 9.0, preferably about 6.0 to 8.0, and is preferably adjusted to about 7.0 before use.
In addition, isotonizing agents include sugars, polyalcohols (mannitol, sorbitol, etc.), sodium chloride, and the like. Thickeners and stabilizers include synthetic organic polymer compounds such as polyvinyl alcohol, poly-N-vinylpyrrolidone, polyethylene glycol, polypropylene glycol, and polyacrylamide, and cellulose derivatives such as hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropylmethyl cellulose. , carboxymethyl starch sodium, starch derivatives such as hydroxyethyl starch, chondroitin sulfate, hyaluronate and the like.

<Medical device base material, form and application of medical device laminate>
The medical device base material and medical device laminate according to the present invention may be in the form of a three-dimensional molded body, a sheet, or a thread. Examples of sheet-like materials include films, non-woven fabrics, and paper.

Applications of the medical device base material and the medical device laminate of the present invention are not particularly limited as long as they are medical equipment, and specific examples include blood bags, urine collection bags, blood transfusion sets, sutures, drain tubes, Various catheters, blood accesses, blood circuits, artificial blood vessels, artificial kidneys, artificial heart lungs, artificial valves, plasma exchange membranes, various adsorbents, CAPD, IABP, pacemakers, artificial joints, artificial femoral heads, dental materials, various shunts, etc. .
Specific examples of such medical device substrates and medical device laminates include silicone-containing medical devices, silicone substrates having microchannels, and preferably silicone-containing microchannel devices. be done.

Examples of the microfluidic device include microanalysis devices such as microreaction devices (specifically, microreactors, microplants, etc.), integrated nucleic acid analysis devices, microelectrophoresis devices, and microchromatography devices; Microdevices for analysis sample preparation such as liquid chromatography; physicochemical processing devices used for extraction, membrane separation, dialysis, etc.; environmental analysis chip, clinical analysis chip, gene analysis chip (DNA chip), protein analysis chip (proteome chip) , sugar chain chips, chromatography chips, cell analysis chips, and pharmaceutical screening chips. Among these, a microchannel chip is preferable.

The microfluidic device is a portion through which a small amount of sample (preferably liquid sample) flows, and the width and depth of the channel are not particularly limited. , preferably 10 μm to 800 μm. The channel width and depth of the microchannel may be the same over the entire length of the channel, or may be partially different in size and shape.

The present invention will be described in more detail with reference to the following examples, but the following examples are not intended to limit the scope of the present invention. In addition, "parts" and "%" in the examples represent "parts by mass" and "% by mass", respectively.

<Reactive silicone oil (A)>
Reactive silicone oil (A1-1): Shin-Etsu Chemical one-end methacrylic group-modified silicone oil X-22-174ASX
Reactive silicone oil (A1-2): Shin-Etsu Chemical one-end methacrylic group-modified silicone oil X-22-174BX
Reactive silicone oil (A2-1): Shin-Etsu Chemical's one-end epoxy group-modified silicone oil X-22-173BX
Reactive silicone oil (A2-2): Shin-Etsu Chemical side chain type epoxy group-modified silicone oil KF-1001
Reactive silicone oil (A3-1): Shin-Etsu Chemical's one-end diol group-modified silicone oil X-22-176DX
Reactive silicone oil (A3-2): Shin-Etsu Chemical's one-end diol group-modified silicone oil X-22-176F

<Preparation of polydimethylsiloxane resin (B)>
Polydimethylsiloxane resin (B-1) and polydimethylsiloxane resin (B-2) were obtained by blending Sylard 184 and Sylard 186 manufactured by Dow Corning Toray in a mass ratio of 10:1.

<Production and evaluation of base material for medical devices>
<Preparation of base material (D) for medical device>
[Examples 1 to 12, Comparative Examples 1 to 3]
Reactive silicone oils (A1-1, 2), (A2-1, 2), (A3-1, 2) at the compounding ratio shown in Table 1, each of which is a polydimethylsiloxane resin (B-1), After blending and preparing with polydimethylsiloxane resin (B-2), 1.6 g was uniformly poured into a non-treatment dish 1010-060 manufactured by IWAKI, and vacuum heat curing was performed at 65 ° C. for 6 hours. Then, the film peeled from the dish was taken out with tweezers to obtain medical device substrates (D-1 to D-15) having a diameter of 60 mm and a thickness of 500 μm.
The medical device substrate (D-15) could not be peeled from the dish because the reactive silicone oil (A3-1) bleed from the polydimethylsiloxane resin (B-1).

[Water contact angle]
The contact angles with water of the medical device substrates (D-1 to D-14) were measured according to the method of JISK6788 (ISO8296).
The evaluation results are shown in Table 1. shown in

[Examples 13 to 24, Comparative Examples 4 and 5]
<Production of coating agent (C)>
Coating agent (C1-1, 3)
Lipdure [LIPIDURE-PMB] manufactured by NOF Corporation and: The copolymer synthesized in Synthesis Example 9 of International Publication WO2017-022815 was diluted with ethanol to prepare a 1% solution, (C1-1 ), (C1-3) was obtained.
Furthermore, 75.0 parts of the block polymer synthesized in Production Example 1 of JP-A-2016-112397, and a carbodiimide group-containing compound (manufactured by Nisshinbo Holdings Inc.; Carbodilite V-02) as a curing agent (C2) 25. 0 part was diluted with ethanol to prepare a 1% solution to obtain a coating agent (C1-2).
The obtained coating agent (C) is shown in Table 2.
Abbreviations in Table 2 are as follows.
C2: Carbodiimide group-containing compound (manufactured by Nisshinbo Holdings Inc.; Carbodilite V-02)

Medical device substrates (D-1 to D-14) were fixed to a glass substrate (Glass Eagle 2000 manufactured by Corning Inc.) of 100 mm×100 mm and 0.7 mm thickness with double-sided tape.
The obtained coating agents (C1-1, 3) were used as base materials for medical devices (D-1 to 14).
A medical device laminate (S1-14) was obtained by coating with a spin coater so that the finished film thickness after heating at 80° C. for 2 hours was 2.0 μm.
Table 2 shows the resulting medical device laminate (S1-14).

[Water contact angle]
The contact angle with water of the medical device laminate (S1-14) was measured according to JISK6788 (ISO8296).
Table 2 shows the evaluation results.

<Evaluation of medical device laminate>
[Examples 25 to 36, Comparative Examples 6 and 7]
Further, the medical device laminate (S1-14) was placed in a PBS (phosphate buffered saline) container, soaked for 24 hours, taken out, washed lightly with distilled water, left at room temperature for 24 hours, and placed in a vacuum dryer. , dried. The contact angle with water of the dried medical device laminate (S1′-14′) was measured according to the method of JISK6788 (ISO8296).
Table 3 shows the evaluation results.

[Examples 37 to 48, Comparative Examples 8 and 9]
[Adsorbability of protein and reagent]
HRP antibody-enzyme assays were performed to test the adsorbability of proteins and reagents.
The medical device laminate (S1-14) was cut into 11 mm squares and placed in a U-shaped 24-well plate, and 1 ml of HRP-IgG solution diluted 10,000 times with phosphate buffered saline (PBS) was added and immersed. let me After incubating for 1 hour at room temperature, each well was washed 4 times with PBS-T (0.1% Tween20). Dispense 1 ml of the staining solution into each well and incubate at room temperature for 10 minutes. After distributing 1 ml of the reaction stopping solution into each well, absorbance Aλ at 450 nm (sub-wavelength 650 nm) was measured using a MITHRAS2LD943-M2M microplate reader. was measured using The smaller the absorbance Aλ, the lower the antibody protein adsorption and the better. Evaluation was made according to the following criteria.
Staining solution: TMBZ solution (3,3',5,5'-tetramethylbenzidine)
Reaction stop solution: WASH and Stop Solution For ELISA With Solution for ELISA without Sulfuric Acid manufactured by Takara Bio Inc.
HRP-IgG: enzyme, antibody (HORSERADIH PEROXIDASE IMMUNOGLOBULING)
PBS-T: PBS with 0.1% Tween 20 added (evaluation criteria)
◎: A ≤ 0.2 (extremely good)
○: 0.2 < Aλ ≤ 0.6 (good)
△: 0.6 < Aλ ≤ 0.8 (usable)
×: 0.8<Aλ (defective)
Table 4 shows the evaluation results.

[Oxygen permeation test]
The oxygen permeability coefficient (Dk) was measured by the method defined in ISO 18369-4 (FATT method) using a flat electrode cell of an oxygen permeability measuring device (201T, Rehder). (1 Barrer=1×10 ⁻¹¹ O ₂ (STP) cm/cm ² mmHg)
◎: Dk ≥ 300 Barrer (extremely good)
○: 300>Dk≧280 (good)
△: 280>Dk≧20 (usable)
×: 20>Dk (defective)

Table 4 shows the evaluation results.

As shown in Table 1, the medical device substrates (D1 to 12) of the present invention exhibited superior hydrophilicity to the medical device substrates (D13, 14).
As shown in Table 2, the medical device laminates (S1 to 12) of the present invention are more hydrophilic than the medical device substrates (S13, 14), and the coating agent can be applied to the medical device substrate. proceeded swiftly.
As shown in Table 3, the medical device laminate (S1′ to 12′) of the present invention exhibits more hydrophilicity than the medical device base material (S13 medical device base material (S13′, 14′), and the coating The adhesion durability between the layer and the base material for medical devices was improved.
As shown in Table 4, the medical device laminates (S1 to S12) of the present invention have better oxygen permeability than the medical device laminates (S13 and 14), and furthermore have an effect of preventing protein adsorption. showed that it works.

Claims (6)

A base material for a medical device comprising a reactive silicone oil (A) and a polydimethylsiloxane resin (B) (excluding the case where the reactive silicone oil (A) is used),
The viscosity of the reactive silicone oil (A) at 25° C. according to JISZ 8803 is 1 to 17,000 [mm ² /s],
The reactive silicone oil (A) is 0.10 to 50% by mass and the polydimethylsiloxane resin (B) is 50 to 99.9% by mass with respect to the entire base material for medical devices. Base material for medical devices. Claim that the reactive silicone oil (A) is one or more selected from (meth) acryloyl group-modified silicone oil (A1), epoxy group-modified silicone oil (A2), and diol group-modified silicone oil (A3) Item 1. The substrate for medical devices according to item 1. Reactive silicone oil (A) is
terminal (meth)acryloyl group-modified silicone oil (A1) having a functional group equivalent of 100 to 12,000 g/mol;
A side chain or single end epoxy group-modified silicone oil (A2) having a functional group equivalent weight of 250 to 5,000 g/mol, and
3. The substrate for medical devices according to claim 1, which is one or more selected from one-end diol group-modified silicone oils (A3) having a functional group equivalent weight of 1 to 1,000 g/mol. A medical device laminate obtained by laminating the medical device substrate according to any one of claims 1 to 3 and a coating layer (Y). 5. The medical device according to claim 4, wherein the medical device laminate has an oxygen permeability coefficient (Dk) according to ISO18369-4 (FATT method) of 280 Barrer (1 Barrer=1×10 ⁻¹¹ O ₂ (STP) cm/cm ² mmHg) or more. Device stack. A method for producing a substrate for medical devices according to any one of claims 1 to 3 ,
Alkenyl group-containing polyorganosiloxane and SiH group-containing organohydrogenpolysiloxane are reacted to form a polydimethylsiloxane resin (B), and then mixed with a reactive silicone oil (A). How the material is made.