WO2008023604A1

WO2008023604A1 - Compound for surface modification and surface modifying method using the same

Info

Publication number: WO2008023604A1
Application number: PCT/JP2007/065839
Authority: WO
Inventors: Yasuhiko Iwasaki; Kazuhiko Ishihara
Original assignee: National University Corporation, Tokyo Medical And Dental University; The University Of Tokyo
Priority date: 2006-08-21
Filing date: 2007-08-14
Publication date: 2008-02-28
Also published as: JPWO2008023604A1

Abstract

Disclosed is a compound for surface modification which is capable of modifying the surface of a hydrophobic base, which is composed of a silicone or the like, for providing lubricity thereto. Also disclosed are a surface modifying method using such a compound for surface modification, a surface-modified hydrophobic base and a surface-modified medical member. Specifically disclosed is a compound for surface modification which is obtained by polymerizing a polymer (B) composed of a radically polymerizable hydrophilic monomer to a polysiloxane compound (A) having a vinyl group in a side chain through a chain transfer agent or a halogenated alkyl initiator. During surface modification, the surface of a hydrophobic base may be hydrosilylated if necessary, and then processed with a solution containing the compound for surface modification. Alternatively, the surface of a hydrophobic base is coated with the compound for surface modification by plasma polymerization.

Description

Specification

Surface modifying compound and surface modification method using the same

Technical field

The present invention relates to a surface modification compound suitable for use in modifying the surface of a hydrophobic substrate such as silicone and a surface modification method using the same.

Background art

In recent years, artificial joints have been widely used as substitutes for joints in the medical field related to humans and other animals. For example, in Japan alone, tens of thousands of operations are performed annually in Japan alone, with a combination of a bone head member made of a metal material such as stainless steel, cobalt chrome alloy, or titanium alloy and a acetabulum made of resin such as ultrahigh molecular weight polyethylene. It is used for. In this way, by replacing each joint with an artificial joint, patients can improve their quality of life (QOU) until they live a life similar to that of a healthy person.

[0003] However, the artificial joint is subject to wear because friction occurs at the sliding portion due to the operation of daily life. The wear powder generated by the wear has an adverse effect on the human body, and when the wear progresses! / So-called loose looseness, the function as an artificial joint becomes difficult to fully function.

[0004] Therefore, in order to prevent such wear, the following Patent Document 1 describes that the sliding surface of the artificial joint is made of a polymer having a phosphorylcholine group, for example, a heavy polymer composed of 2-methacryloyloxychetyl phosphorylcholine. A method of forming a coalescence (called MPC polymer) is described! /. In the method described in Patent Document 1, the material to be treated made of ultra high molecular weight polyethylene is immersed in an acetone solution containing benzophenone, further immersed in an aqueous solution containing MPC, and then irradiated with ultraviolet light. MPC polymer is synthesized on the surface of the workpiece. By forming the sliding surface of the artificial joint with MPC polymer in this way, lubricity is imparted to the sliding surface and wear is suppressed.

[0005] Further, not only artificial joints but also medical members such as catheters, balloon catheters, guide wires, fiberscope endoscopes, contact lenses, etc., it has been proposed to coat the surface with a hydrophilic polymer or the like. ing. For example, in Patent Document 2 below, A medical member made of a polymer material is immersed in a solution containing a diisocyanate compound, and further immersed in a solution containing a mixture of a polyalkylene oxide and a polyurethane prepolymer, whereby the surface of the medical device is lubricated. A method for imparting is described. Patent Document 1: JP 2003-310649 A

Patent Document 2: Japanese Patent Laid-Open No. 2005-287845

Disclosure of the invention

Problems to be solved by the invention

[0006] However, since the method described in Patent Document 1 synthesizes MPC polymer on the surface of the member to be processed by irradiating with ultraviolet light, the MPC depends on the shape of the non-treated member. There was a possibility that the polymer was not synthesized well and the lubricity was insufficient. Here, as a method for performing surface modification simply and effectively, it is possible to immerse the member to be treated in a solution containing MPC polymer. MPC polymer is hydrophilic and has high polarity such as water. It is only soluble in solvents. Therefore, it is difficult to apply to surface modification of hydrophobic substrates such as silicone.

[0007] On the other hand, the method described in Patent Document 2 described above requires a coating of a diisocyanate compound and then a mixture of a polyalkylene oxide and a polyurethane prepolymer, which is favorable in terms of operability. In addition, since it is necessary that a functional group such as a hydroxyl group that reacts with a diisocyanate compound be present on the surface of the medical member, it is not suitable for surface modification of a hydrophobic substrate.

[0008] The present invention has been proposed in view of the problems as described above, and is suitable for use in modifying the surface of a hydrophobic substrate such as silicone to impart lubricity. It is an object of the present invention to provide a medical compound, a surface modification method using the same, and a surface-modified hydrophobic substrate and a medical member.

Means for solving the problem

[0009] As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that a compound obtained by polymerizing a hydrophilic polymer with a polysiloxane compound having a bur group in the side chain is a surface modification of the hydrophobic substrate. As a result, the present invention was completed. More specifically, the present invention provides the following. [0010] (1) A polymer (B) composed of a hydrophilic monomer capable of radical polymerization is polymerized via a chain transfer agent or an alkyl halide initiator on a polysiloxane compound (A) having a bur group in the side chain. Compound for surface modification.

[0011] According to the surface modifying compound of (1), a polysiloxane compound having a bur group in the side chain

Since it has (A), it can be bonded to the surface of the hydrophobic substrate via a bur group. In addition, since it has a polymer (B) composed of a hydrophilic monomer, lubricity can be imparted to the surface of the hydrophobic substrate after surface modification. In particular, after the surface modification, the polymer (B) is arranged in a cilia shape on the surface of the hydrophobic substrate. Therefore, the cilia-like polymer (B) retains the liquid and maintains the lubricity. Furthermore, the surface of the hydrophobic substrate after surface modification is suitable for surface modification of medical members because non-specific adsorption of biological substances and the like is suppressed.

[0012] (2) The surface modifying compound according to (1), wherein the polymer (B) is polymerized on both ends of the polysiloxane compound (A) via a chain transfer agent, or a halogenated alkyl initiator. .

[0013] According to the embodiment of (2), since the polymer (B) is polymerized at both ends of the polysiloxane compound (A)! /, The polymer (B) at both ends is polymerized after the surface modification. It is arranged in a cilia-like manner on the surface of the hydrophobic substrate. Therefore, the lubricity of the hydrophobic substrate surface can be further enhanced.

[0014] (3) The polysiloxane compound (A) contains in its structure a copolymer of a structural unit (al) derived from dimethylsiloxane and a structural unit (a2) derived from a butylmethylsiloxane force. The surface modifying compound according to (1) or (2).

[0015] According to the embodiment of (3), the polysiloxane compound (A) is a copolymer of the structural unit ( _a 1) derived from 1S dimethylsiloxane and the structural unit ( _a 2) derived from butylmethylsiloxane. Is included in the structure, and therefore, the force S is bonded to the surface of the hydrophobic substrate via the bull group of the structural unit (a2).

[0016] (4) The surface modifying compound according to (3), wherein the polymer (B) comprises a structural unit (b) from which 2-methacryloyloxychetyl phosphorylcholineca is also derived.

[0017] According to the embodiment (4), the polymer (B) is composed of the structural unit (b) induced by the 2-methacryloyloxychetyl phosphorylcholine force, and is therefore excellent in biocompatibility. Therefore, it is particularly suitable for surface modification of medical members. [0018] (5) The surface modifying compound according to (3), wherein the polysiloxane compound (A) is represented by the following general formula (1).

[Chemical 1

—— (1)

[In the formula (1),

R ² independently represents an alkylene group having 1 to 4 carbon atoms, and 1 and m represent the number of polymerizations of the structural unit (al) and the structural unit (a2), respectively. ]

According to the aspect (5), since the polysiloxane compound (A) has a structure represented by the general formula (1), it is particularly preferable as the structure of the surface modifying compound.

[0020] (6) The surface modifying compound according to (3), wherein the molar ratio of the structural unit (al) to the structural unit (a2) is 1: 9 to 9: 1.

[0021] According to the aspect (6), since the molar ratio of the structural unit (al) to the structural unit (a2) is in the above range, it can be stably bonded to the surface of the hydrophobic substrate.

[0022] (7) The surface modifying compound according to (4), wherein the molar specific power between the structural units (al) and (a2) and the structural unit (b) is 1: 9 to 9: 1.

[0023] According to the aspect (7), since the molar ratio between the structural units (al) and (a2) and the structural unit (b) is in the above range, the surface is stably bonded to the surface of the hydrophobic substrate. However, it can provide sufficient lubricity.

[0024] (8) The surface modifying compound according to any one of (1) to (7), having a mass average molecular weight of 1,000 to 100,000.

[0025] According to the aspect (8), since the mass average molecular weight is in the above range, the force S is preferably used for surface modification.

[0026] (9) The surface modification according to any one of (1) to (8), wherein the polymer (B) is obtained by polymerizing the hydrophilic monomer on the polysiloxane compound (A) by living radical polymerization. Compounds.

[0027] According to the embodiment of (9), a hydrophilic monomer is polymerized into a living radical polymerization (reversible addition-fragmentation chain transfer (RAFT) polymerization or atom transfer radical polymerization (ATR)) to the polysiloxane compound (A). Since it is polymerized by P)), it can be suitably used for surface modification with a narrow molecular weight distribution.

[0028] (10) Used for surface modification of a hydrophobic substrate having Si—H groups or having Si—H groups introduced therein (1) to (9) For surface modification according to V, deviation Compound.

[0029] (11) The surface modifying compound as described in (10), which is used for surface modification of a substrate made of silicone or ceramics.

[0030] According to any one of the aspects (1) to (9), the surface of a hydrophobic substrate having a Si-H group or having a Si-H group introduced therein, particularly a substrate made of silicone or ceramics Suitable for use in reforming.

[0031] (12) The surface of the hydrophobic substrate having a Si—H group or having a Si—H group introduced therein is treated with a solution containing the surface modifying compound according to any one of (1) to (11). A surface modification method comprising: a treatment step; and a step of heating the hydrophobic substrate treated with a solution containing the surface modification compound.

[0032] (13) The surface modification method according to (12), further comprising a step of hydrosilylating the surface of the hydrophobic substrate and introducing Si—H groups.

[0033] According to the embodiments of (12) and (13), the surface of the hydrophobic substrate is hydrosilylated in advance as necessary, and the bull group is formed by treating with a solution containing the surface modifying compound. Thus, the surface modifying compound can be bonded to the surface of the hydrophobic substrate. Further, since the compound for surface modification has a polymer (B) composed of a hydrophilic monomer, it can impart lubricity to the surface of the hydrophobic substrate after the surface modification. In particular, after the surface modification, the polymer (B) is arranged in a cilia-like manner on the surface of the hydrophobic substrate. Therefore, the cilia-like polymer (B) retains the liquid and maintains the lubricity. Furthermore, the surface of the hydrophobic substrate after surface modification is suitable for surface modification of medical members because nonspecific adsorption of biological substances and the like is suppressed.

[0034] (14) A surface modification method comprising a step of coating the surface of a hydrophobic substrate with the surface modification compound according to any one of (1) to (11) by a plasma polymerization method.

[0035] According to the aspect (14), although an apparatus for plasma polymerization is required, the compound for surface modification can be bonded to the surface of the hydrophobic substrate. Again, after surface modification Since the coalesced (B) is arranged in the form of cilia on the surface of the hydrophobic substrate, the ciliary polymer (B) retains the liquid and maintains the lubricity. In addition, non-specific adsorption of biological substances and the like is suppressed on the surface of the hydrophobic substrate after surface modification.

[0036] (15) A hydrophobic substrate surface-modified using the surface modifying compound according to any one of (1) to (11).

[0037] (16) A medical member having a surface modified with the surface modifying compound according to any one of (1) to (11).

[0038] According to the embodiments of (15) and (16), there are provided a hydrophobic substrate and a medical member to which lubricity is imparted by surface modification and nonspecific adsorption of a biological substance or the like is suppressed. be able to. The invention's effect

[0039] According to the present invention, lubricity can be imparted to the surface of a hydrophobic substrate by modifying the surface of a hydrophobic substrate such as silicone using the surface modifying compound of the present invention. . In addition, by performing surface modification of the hydrophobic substrate using the surface modifying compound of the present invention, nonspecific adsorption of biological substances or the like on the surface of the hydrophobic substrate can be suppressed.

Brief Description of Drawings

[0040] FIG. 1 is a graph showing the relationship between polymerization time and MPC concentration.

FIG. 2 is a graph showing the relationship between the polymerization time and the molecular weight of the surface modifying compound.

FIG. 3 is a diagram showing a procedure for applying surface modification to a test piece.

FIG. 4 is a graph showing the surface analysis results of a test piece after surface modification.

FIG. 5 is a graph showing a comparison of the coefficient of friction of test pieces with and without surface modification.

FIG. 6 is a diagram showing non-specific adhesion of platelets with and without surface modification.

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, specific embodiments to which the present invention is applied will be described in detail.

[Surface modifying compound]

The compound for surface modification of the present invention is a polysiloxane compound having a bur group in the side chain (A

) And a polymer (B) composed of a hydrophilic monomer capable of radical polymerization is polymerized via a chain transfer agent or a halogenated alkyl initiator.

[0043] [Polysiloxane compound (A)] The polysiloxane compound (A) is not particularly limited as long as it has a bull group in the side chain. This polysiloxane compound (A) is hydrophobic and can be bonded to the surface of the hydrophobic substrate via a vinyl group as described later.

[0044] Among such polysiloxane compounds (A), those having a hydroxyl group at one or both ends for introducing a chain transfer agent or a halogenated alkyl initiator are preferred. By introducing a chain transfer agent or an alkyl halide initiator through this hydroxyl group, the polymer (B) can be polymerized at one or both ends of the polysiloxane compound (A). The polysiloxane compound (A) is preferable because it can polymerize the polymer (B) at both ends, and the effect of surface modification can be further enhanced.

[0045] Among the polysiloxane compounds (A), those containing a copolymer of a structural unit (al) derived from dimethylsiloxane and a structural unit (a2) derived from butylmethylsiloxane force in the structure. Those having a structure represented by the following general formula (1) are more preferable.

[Chemical 2]

—— (1)

[In the formula (1),

[0046] Each R ² independently represents an alkylene group having 1 to 4 carbon atoms. Examples of the alkylene group having a carbon number of! To 4 include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group and the like, and a group from which one hydrogen atom has been removed.

An example of a preferred combination of R ² includes = propylene group and R ² = ethylene group. In addition, 1 and m represent the number of polymerization of the structural unit (a 1) and the structural unit (a2), respectively.

[0047] The molar ratio of the structural unit (al) to the structural unit (a2) is preferably 1: 9 to 9: 1. More preferably, it is 3: 7 to 7: 3. By setting the content in the above range, the surface modifying compound can be stably bonded to the surface of the hydrophobic substrate.

[0048] [Polymer (B)] The polymer (B) can be used without particular limitation as long as it is composed of a radically polymerizable hydrophilic monomer, such as acrylamide, N-butylpyrrolidone, and polyethylene glycol methacrylate. This polymer (B) is hydrophilic and can impart lubricity to the surface of the hydrophobic substrate.

[0049] Among such polymers (B), a polymer obtained by polymerizing a structural unit (b) derived from 2 methacryloyloxyphosphorylcholine shown in the following structural formula (2). Particularly preferred for modification. 2-Methacryloyloxychetylphosphorylcholine is known to have the same polarity as the phospholipid molecules constituting the biological membrane and is excellent in biocompatibility.

[Chemical 3

CH ₃ 0 "CH ₃

CH ₂ = C 1 C— O— CH ₂ — CH ₂ — 0— P— 0—CH ₂ — CH ₂ — N + — CH ₃

II II \

OO CH ₃ (2)

[0050] Here, when the polysiloxane compound (A) having the structural units (al) and (a2) is used, the molar ratio of the structural units (al) and (a2) to the structural unit (b) Is preferably 1: 9 to 9: 1. More preferably, it is 3: 7 to 7: 3. By setting the amount within the above range, the surface modifying compound can be controlled with a force S that imparts sufficient lubricity while stably bonding to the surface of the hydrophobic substrate.

[0051] [Chain transfer agent / alkyl halide initiator]

The polymer (B) is obtained by polymerizing the polysiloxane compound (A) with a hydrophilic monomer by living radical polymerization (reversible addition-fragmentation chain transfer (RAFT) polymerization or atom transfer radical polymerization (ATRP)). (A) is polymerized via a chain transfer agent or an alkyl halide initiator.

[0052] The chain transfer agent used in the case of reversible addition-cleavage chain transfer polymerization is not particularly limited, but includes 4 cyanopentanoic acid dithiobenzoate, acetic acid dithiobenzoate, butanoic acid dithiobenzoate, 4 toluic acid dithiol. Examples include benzoate. [0053] Although the halogenated alkyl initiator used in the case of atom transfer radical polymerization is not particularly limited, 2-bromoisobutyryl bromide, 2-chloroisobutyryl chloride, bromoacetyl bromide, bromoacetyl And chloride.

[0054] According to this living radical polymerization, if the precision synthesis is possible, the molecular weight distribution of the surface modifying compound synthesized by the process becomes narrow (Mw / Mn = l .;! ~ 1. About 5) and can be suitably used for surface modification.

[0055] The surface modifying compound of the present invention preferably has a mass average molecular weight of 1000 to 1000000. More preferably, it is 10,000 to 500,000. By setting the content in the above range, the surface modifying compound of the present invention can be suitably used for surface modification of a hydrophobic substrate.

[0056] [Method for synthesizing compound for surface modification]

The surface modifying compound of the present invention synthesizes a polysiloxane compound (A), introduces a chain transfer agent into the polysiloxane compound (A), and performs chain transfer to the polysiloxane compound (A) by living radical polymerization. It can be synthesized by polymerizing the polymer (B) via an agent or an alkyl halide initiator. The polymer (B) may be synthesized at one end or at both ends of the polysiloxane compound (A) .In the following, as an example, the polymer (B) is synthesized at both ends of the polysiloxane compound (A). Explain how to synthesize!

[0057] First, the polysiloxane compound (A) is synthesized. This polysiloxane compound (A) is, for example, a hydroxyl group or a hydroxyl group-terminated functional group bonded to both ends (dimethylsiloxane) as a starting material, and otamethylcyclotetrasiloxane and tetramethyltetrabule. Synthesized by adding ring-opening polymerization reaction by adding cyclotetrasiloxane in a desired ratio.

[0058] Next, a chain transfer agent or an alkyl halide initiator is introduced into the polysiloxane compound (A). This chain transfer agent or alkyl halide initiator is reacted, for example, by adding a dicyclohexyl carpositimide solution dropwise into a solution in which the polysiloxane compound (A) and the chain transfer agent or alkyl halide initiator are dissolved. Can be introduced.

[0059] Next, the polymer (B) is polymerized to the polysiloxane compound (A) via a chain transfer agent or a halogenated alkyl initiator by living radical polymerization. This polymerization reaction is reversible In the case of addition-cleavage chain transfer polymerization, the polysiloxane compound (A) having a chain binder introduced therein and a hydrophilic monomer are dissolved in a predetermined solvent, a polymerization initiator is added, and the mixture is added at 50 to 80 ° C. Performed by heating for ~ 48 hours. In addition, in the case of atom transfer radical polymerization, the polysiloxane compound (A) in which an alkali halide initiator is introduced and a hydrophilic monomer are dissolved in a predetermined solvent, a transition metal complex is added, and 25 to 80 ° C is added. For 2 to 48 hours.

[0060] The solvent used in the polymerization reaction is not particularly limited, but water, methanol, ethanol, propanol, tert-butanol, benzene, toluene, dimethylformamide, tetrahydrofuran, chloroform, or a mixture thereof can be used. Can be mentioned.

[0061] The polymerization initiator is not particularly limited, but 2,2'-azobisisoptyronitrile, benzoyl peroxide, diisopropyl peroxycarbonate, t-butyl peroxy 2-ethino hexanoate, tert-butyl olepenoleoxy Pivalate, t-butinolepenoleoxydiisoptylate, persulfate, persulfate bisulfite, and the like can be used.

[0062] The transition metal complex is not particularly limited, and complexes such as monovalent copper and divalent ruthenium can be used.

[0063] [Surface modification method]

The first surface modification method of the present invention comprises a step of treating the surface of a hydrophobic substrate having Si—H groups or having Si—H groups introduced therein with a solution containing the surface modification compound of the present invention. And heating the hydrophobic substrate treated with the solution containing the surface modifying compound.

[0064] If the hydrophobic substrate does not have Si-H groups, the surface of the hydrophobic substrate may be hydrosilylated to further include a step of introducing Si-H groups. . This hydrosilation can be achieved by known methods such as immersing the hydrophobic substrate in a poly (hydromethylsiloxane) solution, for example.

First, the surface of the hydrophobic substrate having Si—H groups or having Si—H groups introduced therein is treated with a solution containing the surface modifying compound of the present invention. In this step, it may be applied by a known coating method such as a spin coating method in which a hydrophobic substrate may be immersed in a solution containing a surface modifying compound. [0066] The solvent of the solution containing the surface modifying compound is not particularly limited, but methanol, ethanol, isopropanol, or a mixed solution thereof can be used. The compound for surface modification is dissolved in this solvent at a concentration of 0.0; The solution contains a catalyst such as a Pt catalyst.

Next, the surface modifying compound is bonded to the surface of the hydrophobic substrate by heating the hydrophobic substrate treated with the solution containing the surface modifying compound. The heating temperature is preferably 35 to 80 ° C. By this heating, the Si—H group of the hydrophobic substrate is bonded to the bull group of the polysiloxane (A) of the surface modifying compound. Note that the time required for bonding can be shortened by increasing the heating temperature.

[0068] On the surface of the hydrophobic substrate thus modified, the polysiloxane compound (A) is fixed via a vinyl group, and the polymer (B) is arranged in a cilia shape. Accordingly, the liquid is held by the ciliated polymer (B) and the lubricity is maintained. In addition, non-specific adsorption of biological substances and the like is suppressed on the surface of the hydrophobic substrate after surface modification.

[0069] The second surface modification method of the present invention includes a step of coating the surface of the hydrophobic substrate with the surface modification compound of the present invention by a plasma polymerization method.

[0070] According to such a surface modification method, an apparatus for plasma polymerization is required, but the surface modification compound can be bonded to the surface of the hydrophobic substrate. Also in this case, after the surface modification, the polymer (B) is arranged in a cilia shape on the surface of the hydrophobic substrate, so that the liquid is retained by the ciliated polymer (B) and the lubricity is maintained. The In addition, non-specific adsorption of biological substances and the like is suppressed on the surface of the hydrophobic substrate after surface modification.

[Hydrophobic substrate, medical member]

The hydrophobic substrate of the present invention has been modified with the surface modifying compound of the present invention. Examples of the hydrophobic substrate include silicone, ceramics, glass, metal, and semiconductor nanoparticles. Among these, silicone and ceramics are preferable.

[0072] Further, the medical member of the present invention has been modified using the surface modifying compound of the present invention. This medical member is manufactured using a hydrophobic base material that has been surface-modified in advance, even if it has been surface-modified to a medical member that has already been manufactured. There may be. Medical members include artificial joints, catheters, balloon force tables Examples include treatment machine instruments such as drills and guide wires, inspection instrument instruments such as fiberscope endoscopes, and ophthalmic members such as contour lenses.

Example

[0073] Hereinafter, the present invention will be described in more detail with reference to examples.

[0074] <Synthesis of surface modifying compound>

[Synthesis of polysiloxane compounds]

The following reaction scheme shows the following: ■ Hydroxyethoxypropyl-dimethylsilyl group S Poly (dimethylsiloxane co butylmethylsiloxane) bonded at both ends (PD V M

1 m

S) was synthesized.

[Chemical 4

C / DH

0 I 0

M ^R ₂ D ₈

(e ₂ SiO) ₄

(MeViSiO) ₄

PD, V _m MS

Hydroxyethoxypropyl butyldimethylsilyl group is bonded to both ends oligo (Jimechirushi port ^{hexane) (M R D, n =} 8) (manufactured by Shin-Etsu Chemical Co.) was used as a starting material, OTA data methylcyclopropyl

2 8

Tetrasiloxane ((Me SiO)) (manufactured by Shin-Etsu Chemical Co., Ltd.) and tetramethyltetraburushiku

twenty four

Add rotetrasiloxane ((MeViSiO)) (manufactured by Shin-Etsu Chemical Co., Ltd.) at a ratio of about l: m

Four

PD V MS was synthesized by causing a ring-opening polymerization reaction. Type of synthesized PD V MS, M ^R D as a raw material, (Me SiO), and (MeViSiO)

1 m 2 8 2 4

Molar amount, Me SiO and MeViSiO mole fraction, synthesized PD V MS mass average

4 2 1 m

The molecular weight (Mw) and dispersity (Mw / Mn) are shown in Table 1. The apparent molecular weight was measured by gel filtration chromatography (GPC), and the absolute molecular weight was measured by a multi-angle light scattering detector (MALL S).

[table 1]

a) Theoretical value, ^b) Apparent molecular weight measured by GPG, ^e) Absolute molecular weight measured by MALLS First, as shown in the following reaction scheme, a chain transfer agent (CTA) is attached to both ends of PD V MS.

1 m

Was introduced to synthesize CTA-PD V MS—CTA.

1 m

[Chemical 5] One _i _ _Q ^. ~ OH + PD | V _m MS CTA

DCC CH ₂ CI ₂

CTA-PD | V _m S-CTA 4 Cyananopentanoic acid dithiobenzoate was used as the chain transfer agent and this was added to McC Synthesized according to the method of ormic et al. (Mitsukami, Y .; Donovan, MS; Lowe, AB; McCormick, CL Macromolecules 2001, 34, 2248). Di-solubilized a given amount of PD V MS and a 4-fold molar amount of 4-cyanopentanoic acid dithiobenzoate

1 m

Chloromethane (in CH CI UOOmL, dicyclohexyl dissolved in lOOmL of dichloromethane)

twenty two

Lucal positive imide (DCC) (manufactured by Kanto Chemical Co., Inc.) was added dropwise and stirred at 40 ° C for 20 hours. Thereafter, insoluble matters were removed by filtration through a filter. Next, the dichloromethane was distilled off, and the reaction product was washed with methanol until the methanol was no longer colored, and then dissolved in chloroform. Then, after washing three times with saturated saline, the water was removed with magnesium sulfide and concentrated.

Next, as shown in the reaction scheme below, CTA-PD V MS—

1 m

Methacryloyloxetyl phosphorylcholine (MPC) was polymerized to synthesize PMPC -PD V MS -PMPC, a surface modification compound.

n 1 m n

[Chemical 6]

CTA-PD | V _m S-CTA

MPC

15 mmol of MPC (manufactured by NOF Corporation) and a predetermined amount of CTA—PD V MS—CTA

1 m

Dissolved in an ethanol / ethanol (1/1) solution, the total volume was adjusted to 30 mL. Next, after adding a predetermined amount of 2,2'-azobisisoptyronitrile (AIBN) (manufactured by Kanto Chemical Co., Inc.) as a polymerization initiator, oxygen was removed by passing argon gas through the solution for 30 minutes. did. Then, PMPC -PD V M n 1 m by reacting for a predetermined time with gentle stirring at 70 ° C

S—PMPC was synthesized. The synthesized PMPC -PD V MS—PMPC Precipitation was performed in lahydrofuran, and the precipitate was dissolved in ethanol, and then precipitated again in tetrahydrofuran. Finally, the precipitate was dried under reduced pressure.

[0081] Fig. 1 shows the relationship between the polymerization time and the MPC concentration when the molar amounts of MPC, CTA, and AIBN as raw materials are 15 mmol, 0.05 mmol, and 0.025 mmol, respectively. In FIG. 1, M represents the initial concentration of MPC, and M represents the MPC concentration at a certain time point.

0

Figure 2 shows the relationship between the polymerization time and the molecular weight of PMPC -PD V MS -PMPC.

n 1 m n

Since the MPC polymerization reaction in the present invention is a living radical reaction, the rate of decrease in MPC concentration is almost constant as shown in Fig. 1, and the molecule of PMPC -PD V MS -PMPC

n 1 m n

The amount increases as shown in Figure 2 with decreasing MPC concentration.

[0082] Type and code of synthesized PMPC -PD V MS -PMPC, MPC as raw material,

n 1 m n

Molar amount of CTA and AIBN, number of polymerizations of PMPC (PMPC), synthesized PMPC-PD

PDI n 1

The molecular weight of V MS -PMPC is shown in Table 2. The number of polymerizations of PMPC in the compound m n

Was measured by phosphorus quantification.

[Table 2]

[MPC] = 0.5mol / L [CTA] / [AIBN] = 2 Polymerization temperature = 70 ° C Solvent: Ethanol / Toluene = 1/1 (vol)

[0083] <Surface Modification of Specimen Using Surface Modification Compound>

Using the synthesized surface modifying compound, the surface modification of a silicone test piece was performed in the procedure shown in FIG.

[0084] [Preparation of test piece and hydrosilylation]

First, PDMS prepolymer (Silpotl8 ^4, Dow 'Koyungu Co.) and 1 0 of the crosslinking catalyst: 1 and stirred well a mixture of (w / w), was added dropwise a Teflon plate. That Thereafter, it was deaerated and cured by heating at 100 ° C. for 2 hours. The cured film was peeled off from the plate and processed into a disk shape with a diameter of 15 mm. The obtained disc-shaped test piece was washed with hexane and acetone and dried at room temperature under reduced pressure for 1 day.

[0085] Next, 30 ml of a 3: 5 (v / v) mixed solution of poly (hydromethylsiloxane) (KF99P, manufactured by Shin-Etsu Chemical Co., Ltd.) and isopropanol monore was added as a catalyst with 0.02 ml of trifluoro. The test piece was hydrosilylated by immersing the test piece in a solution containing romethanesulfonic acid and stirring at room temperature for 15 minutes. Thereafter, the test piece was taken out of the solution, washed thoroughly with isopropanol and hexane, and then dried at room temperature under reduced pressure for 1 day. The Si—H group on the specimen surface was confirmed by total reflection absorption Fourier transform infrared spectroscopy (ATR—FTIR).

[0086] [Surface Modification of Specimen]

Two drops of Pt catalyst (platinum dibule tetramethyldisiloxane complex) were added to 10 mL of ethanol containing 1% by mass of a surface modifying compound to prepare a polymer solution. This polymer solution was dropped on the test piece after hydrosilylation and spin-coated at 4000 rpm for 10 minutes. Thereafter, the surface modifying compound was bonded to the test piece by heating at 80 ° C. for 2 hours. Then, the test piece was immersed in ethanol, rinsed at 50 ° C. for 24 hours while ethanol was being exchanged, and then dried under reduced pressure.

[0087] <Surface analysis after surface modification>

In order to confirm whether or not the surface modifying compound was bound to the surface-modified test piece, the surface of the test piece after the surface modification was analyzed with an X-ray photoelectron spectrometer (XPS). Figure 4 shows the ratio (P / C) of the phosphorus atom signal to the carbon atom signal. In FIG. 4, for example, “26-173” means the code of the surface modifying compound shown in Table 2, that is, PMPC.

26

-PD V MS Represents PMPC.

173 17 26

[0088] As shown in Fig. 4, although there is a slight difference depending on the number of polymerized components, a signal of a phosphorus atom derived from MPC was confirmed, and the surface modifying compound was bound to the test piece. And! /, The power of S.

[0089] <Measurement of friction coefficient>

The lubricity of the test piece was evaluated by measuring the coefficient of friction of the test piece after surface modification. Place a 25 mm diameter stainless steel disk on the test piece via pure water as a lubricant. The coefficient of static friction and the coefficient of dynamic friction were measured by sliding this stainless steel disk at a speed of 10 mm / s with a load of lOOg. The results are shown in Fig. 5 (A) and (B). FIG. 5B is an enlarged view of a portion surrounded by a broken line in FIG.

[0090] As can be seen from Figs. 5 (A) and (B), the coefficient of static friction of the test piece surface-modified with the surface modifying compound of the present invention is higher than that of the test piece not surface-modified. Both the dynamic friction coefficients are significantly reduced. This is presumably because water as a lubricating liquid was retained by the polymer (B) of the surface modifying compound.

[0091] <Platelet adhesion test>

In order to evaluate the presence or absence of nonspecific adsorption to the test piece after surface modification, a platelet adhesion test was performed. 3. Platelet rich plasma (PRP) was prepared by centrifuging human whole blood with 1/10 volume of 8% sodium citrate added to blood at 12000 rpm for 15 minutes and collecting the supernatant. The sample was fixed to a 24-well culture plate with a silicon ring, and 1 ml of phosphate buffered saline was added to equilibrate. Thereafter, 1 ml of PRP was added to each well and allowed to stand at room temperature for 180 minutes. Figure 6 shows the results of surface observation with a scanning electron microscope (SEM).

[0092] As can be seen from FIG. 6, when the surface was modified with the surface modifying compound of the present invention, the adhesion of the blood platelets was remarkably suppressed. Therefore, the surface modifying compound of the present invention is suitable for surface modification of a medical member that comes into contact with a biological substance or the like.

[0093] The power described in the best mode for carrying out the present invention has been described above. The present invention is not limited only to the above-described embodiment, and various modifications can be made without changing the gist of the present invention. Of course, it is possible.

For example, in the above-described embodiment, the surface modifying compound of the present invention has been described focusing on the effect of imparting lubricity, but the surface modifying compound of the present invention is as shown in FIG. In addition, since non-specific adsorption of biological substances and the like can be suppressed, the biosensor can be suitably used for applications that require less non-specific adsorption rather than lubricity, such as biochips.

Claims

The scope of the claims

[1] Surface modification in which a polymer (B) made of a hydrophilic monomer capable of radical polymerization is polymerized via a chain transfer agent or an alkyl halide initiator to a polysiloxane compound (A) having a bur group in the side chain Compounds.

[2] The surface modifying compound according to claim 1, wherein the polymer (B) is polymerized on both ends of the polysiloxane compound (A) via a chain transfer agent or a halogenated alkyl initiator.

[3] Structural unit derived from the polysiloxane compound (A) force dimethylsiloxane force (al

3) The compound for surface modification according to claim 1 or 2, comprising a copolymer of a structural unit (a2) derived from butylmethylsiloxane in the structure.

4. The surface modifying compound according to claim 3, wherein the polymer (B) is a structural unit (b) force derived from 2-methacryloyloxychetylphosphorylcholine.

5. The surface modifying compound according to claim 3, wherein the polysiloxane compound (A) is represented by the following general formula (1).

[Chemical 1

—— (1)

[In the formula (1),

6. The surface modifying compound according to claim 3, wherein the molar ratio between the structural unit (al) and the structural unit (a2) is 1: 9 to 9: 1.

7. The surface modifying compound according to claim 4, wherein the molar specific force S between the structural units (al) and (a2) and the structural unit (b) is S: 1: 9 to 9: 1.

[8] The compound for surface modification according to any one of [1] to [7], having a mass average molecular weight of 1000 to 1000000.

[9] The surface modification agent according to any one of [1] to [8], wherein the polymer (B) is polymerized by the hydrophilic monomer coupling radical polymerization to the polysiloxane compound (A). Compound.

[10] The surface modifying compound according to any one of claims 1 to 91 /, which is used for surface modification of a hydrophobic substrate having a Si—H group or having a Si—H group introduced therein.

11. The surface modifying compound according to claim 10, which is used for surface modification of silicone or ceramics.

[12] The surface of the hydrophobic substrate having Si—H groups or having Si—H groups introduced therein,

1 1 V, a step of treating with a solution containing the surface modifying compound described in the deviation,

Heating the hydrophobic substrate treated with a solution containing the surface modifying compound.

13. The surface modification method according to claim 12, further comprising the step of hydrosilylating the surface of the hydrophobic substrate and introducing Si—H groups.

[14] A surface modification method comprising a step of coating the surface of a hydrophobic substrate with the surface modification compound according to any one of [1] to [11] by a plasma polymerization method.

[15] A hydrophobic substrate surface-modified with the surface-modifying compound according to any one of claims 1 to 11.

[16] A medical member surface-modified with the surface-modifying compound according to any one of claims 1 to 11.