JP5448529B2 - Polysiloxane and method for producing the same - Google Patents

Description

The present invention relates to polysiloxane, a method for producing polysiloxane, a surface modifier , a surface modification method, and a surface modification material .

  Conventionally, a polymer having a phosphorylcholine group is known as a biocompatible polymer, and biocompatible materials obtained by coating various resin materials with such a polymer are known.

  Patent Document 1 discloses a powder for cosmetics obtained by coating powder with a polymer obtained by polymerizing 2-methacryloyloxyethyl phosphorylcholine as one of the monomers.

  Patent Document 2 discloses a copolymer based on a monomer having a phosphorylcholine-like group in the side chain on the surface of a substrate and a monomer having a group capable of binding to heparin or a heparin derivative, heparin. Or the medical material in which the coating layer comprised from a heparin derivative is formed is disclosed.

  Further, in Patent Document 3, the amount P of phosphorus element derived from the phosphorylcholine-like group and the amount C of carbon element in a spectrum having phosphorylcholine-like groups at least on the surface and measured by X-ray photoelectron spectroscopy of the surface, A separation material having a ratio (P / C) of 0.002 to 0.3 is disclosed.

  On the other hand, Patent Document 4 discloses a polysiloxane having a phosphorylcholine group. However, since such a polysiloxane has a phosphorylcholine group and a silicon atom bonded via an imino group having a pH dependency, when used as a surface modifier, the pH is such that the effect of the phosphorylcholine group can be obtained. There is a problem that there are limitations.

JP 7-118123 A JP 2000-279512 A JP 2002-98676 A JP 2004-175830 A

The present invention provides a polysiloxane having a phosphorylcholine-like group capable of suppressing the restriction of pH when used as a surface modifier, and a method for producing the polysiloxane, in view of the above-described problems of the prior art. For the purpose. Further, the present invention is a surface reforming agent containing the polysiloxane, with the surface modifying agent, the surface of the material using the surface modification method and the surface modifying agent that inquire break, surface modifying It is an object of the present invention to provide a surface modification material that has been improved.

  The invention according to claim 1 is a polysiloxane having a general formula

Wherein R ¹ , R ² and R ³ are each independently an alkyl group having 1 to 6 carbon atoms, and R ⁴ is a hydrogen atom or an alkyl group having 1 to 18 carbon atoms. , X is an alkylene group having 1 to 18 carbon atoms, a polyoxyalkylene group or an arylene group having 1 to 18 units, Y is an amide bond, m is an integer of 2 to 6 .)
It characterized by having a represented Ru configuration units in.

The invention according to claim 2 is a method for producing the polysiloxane according to claim 1, wherein the chemical formula is obtained by oxidizing glycerophosphorylcholine.
It has the process of synthesize | combining the compound represented by these.

The invention according to claim 3 is characterized in that the surface modifier contains the polysiloxane according to claim 1 .

The invention described in claim 4 is characterized in that, in the surface modification method, the surface of the material is modified using the surface modifier described in claim 3 .
The invention described in claim 5 is characterized in that the surface of the surface modifying material is modified by using the surface modifying agent according to claim 3.

ADVANTAGE OF THE INVENTION When using as a surface modifier, according to this invention, the polysiloxane which has the phosphorylcholine analog group which can suppress the restriction | limiting of pH, and the manufacturing method of this polysiloxane can be provided. Further, according to the present invention, a surface modifying agent containing the polysiloxane, with the surface modifying agent, the surface of the material using the surface modification method and the surface modifying agent that inquire breaks, the surface There can be provided a surface modifying material that has been modified.

1 is a diagram showing a ¹ H NMR spectrum of compound B in Example 1. FIG. 1 is a diagram showing an MS spectrum of compound B in Example 1. FIG. 1 is a diagram showing a ¹ H NMR spectrum of compound C in Example 1. FIG. 2 is a diagram showing a ¹ H NMR spectrum of an amino-modified polysiloxane of Example 2. FIG. 2 is a diagram showing a ¹ H NMR spectrum of compound D in Example 2. FIG. It is a figure which shows the evaluation result of the protein adsorption test of an Example.

  Next, the form for implementing this invention is demonstrated with drawing.

  The polysiloxane of the present invention has the general formula (1)

^(Wherein, R 1, ^{R 2} and ^{R 3} are each independently an alkyl group having 1 to 6 carbon atoms, m is an integer from 2 to 6.)
And a structural unit in which an ester bond or an amide bond, a spacer, and an Si atom are sequentially bonded. As a result, a polysiloxane having a phosphorylcholine-like group capable of suppressing the restriction of pH is obtained. In addition, these polysiloxanes can modify the surface of the material regardless of purification or non-purification, and effects such as suppression of protein adsorption can be obtained.

  The polysiloxane of the present invention has the general formula (2)

(Wherein R ⁴ is a hydrogen atom or an alkyl group having 1 to 18 carbon atoms, and X is an alkylene group having 1 to 18 carbon atoms, a polyoxyalkylene group or an arylene group having 1 to 18 units) And Y is an ester bond or an amide bond.)
It is preferable to have the structural unit represented by these. At this time, examples of the polyoxyalkylene group include a polyoxyethylene group and a polyoxypropylene group. Examples of the arylene group include a phenylene group, an oxyphenylene group, and a methylenephenylene group. Further, the alkylene group, polyoxyalkylene group and arylene group may be substituted with other hydrocarbon functional groups.

  The ratio of the structural unit represented by the general formula (2) to all structural units of the polysiloxane of the present invention is preferably 5 mol% or more, and more preferably 20 mol% or more. Thereby, characteristics of phosphorylcholine-like groups such as biocompatibility and moisture retention can be sufficiently expressed.

  The polysiloxane of the present invention comprises a compound having a phosphorylcholine-like group and a carboxyl group represented by the general formula (1), and a structural unit in which a hydroxyl group, an amino group, and an Si atom are bonded via a spacer. It is obtained by condensing.

  In addition, the polysiloxane of the present invention has a structural unit in which a compound having a phosphorylcholine-like group represented by the general formula (1) and a hydroxyl group or an amino group, and a carboxyl group and an Si atom are bonded via a spacer. It is obtained by condensing polysiloxane.

  At this time, for example, a compound having a phosphorylcholine group and a carboxyl group can be obtained by oxidizing glycerophosphorylcholine using periodic acid and ruthenium trichloride. Moreover, the compound which has a phosphorylcholine group, a hydroxyl group, or an amino group is obtained by condensing the compound which has a phosphorylcholine group and a carboxyl group with diol or diamine.

  Furthermore, the polysiloxane of the present invention comprises a phosphorylcholine-like group represented by the general formula (1), an ester bond or an amide bond, a spacer, and a general formula (3).

(In the formula, R ⁵ is a hydrogen atom or an alkyl group having 1 to 18 carbon atoms.)
A vinyl compound in which functional groups represented by the formula are sequentially bonded, and a general formula (2)

It is obtained by adding (hydrosilylation) a polysiloxane having a structural unit represented by:

  As vinyl compounds, general formulas

(In the formula, Z represents a general formula —CH ₂ CHR ⁵ —Z—
Or a functional group represented by the formula: —C (CH ₃ ) R ⁵ —Z—
Is a functional group in which the functional group represented by X is X. )
The compound represented by these is preferable.

  In the vinyl compound, a compound having a phosphorylcholine-like group and a carboxyl group represented by the general formula (1) and a functional group and a hydroxyl group or an amino group represented by the general formula (3) are bonded via a spacer. It can be obtained by condensing the compound.

  The vinyl compound is a compound having a phosphorylcholine-like group represented by the general formula (1) and a hydroxyl group or an amino group, and a functional group and a carboxyl group represented by the general formula (3) bonded via a spacer. It can be obtained by condensing the compound.

  At this time, for example, a compound having a phosphorylcholine group and a carboxyl group can be obtained by oxidizing glycerophosphorylcholine using periodic acid and ruthenium trichloride. Moreover, the compound which has a phosphorylcholine group, a hydroxyl group, or an amino group is obtained by condensing the compound which has a phosphorylcholine group and a carboxyl group with diol or diamine.

  The polysiloxane of the present invention can be used as a surface modifier and is modified by introducing a desired amount of phosphorylcholine-like groups on the surface of the material. At this time, the materials whose surface can be modified include polyethylene, polypropylene, polystyrene, polyvinyl chloride, nylon, polyurethane, polyurea, poly (meth) acrylic acid, poly (meth) acrylate, polyester, poly Examples include acrylonitrile, polyacrylamide, polyvinyl acetate, polycarbonate, polysulfone, polyvinyl alcohol, cellulose, cellulose acetate, silicone resin, glass, ceramic, metal, stainless steel, and the like.

  When modifying the surface of the material using the polysiloxane of the present invention, it is preferable to apply and dry a polysiloxane solution or dispersion on the surface of the material. At this time, vacuum drying, heat treatment, or the like may be performed as necessary. The solvent used for the polysiloxane solution or dispersion is not particularly limited. The concentration of polysiloxane in the solution or dispersion is preferably 0.01 to 30% by weight, more preferably 0.1 to 20% by weight. When this concentration is less than 0.01% by weight, the amount of polysiloxane formed on the surface of the material becomes insufficient, and performance may not be exhibited. On the other hand, if the concentration exceeds 30% by weight, the workability when applying the polysiloxane solution or dispersion may deteriorate, and the uniformity of the coating film may deteriorate. Examples of the coating method include known methods such as a dipping method, a spray method, a roller coating method, and a spin coating method.

[Example 1]
An aqueous solution of L-α-glycerophosphorylcholine was cooled in an ice-water bath. Next, after adding 4 period equivalent sodium periodate of L-α-glycerophosphorylcholine, a catalytic amount of ruthenium trichloride was added, and the mixture was stirred for 3 hours to be reacted. Next, methanol was added and the mixture was further stirred for 30 minutes, and then the precipitate was removed by filtration. Furthermore, after concentration under reduced pressure, drying under reduced pressure, chemical formula

The compound A represented by these was obtained.

  Next, Compound A and 2-fold equivalent carbonyldiimidazole (CDI) of Compound A were added to dimethyl sulfoxide (DMSO), and the mixture was stirred and reacted at room temperature. Furthermore, allylamine is dropped and reacted, and the chemical formula

Compound B (vinyl compound having a molecular weight of 281) represented by the formula (1) was obtained (see FIGS. 1 and 2).

During dehydrated ethanol / dehydrated chloroform mixture, in the presence of a platinum catalyst _{(H 2 PtCl 6 · 6H 2} O), and compound B, the formula

HM151 (manufactured by Gelest) of a trimethylsiloxy-terminated methyl H siloxane-dimethyl siloxane copolymer represented by the formula

The compound C (polysiloxane which has a phosphorylcholine group) represented by these was obtained (refer FIG. 3).

  A 10 wt% methanol solution of Compound C was applied to a polystyrene 96-well plate (Nihon BD). Next, after washing with methanol, it was dried to obtain a surface-treated well plate.

[Example 2]
In a methanol solution of a diamine-type amino-modified polysiloxane (see FIG. 4) having an amine equivalent of 144 g / mol, compound A is added twice as much as amino-modified polysiloxane, and then 1.2 times equivalent of compound A. Triazine type dehydration condensing agent DMT-MM (manufactured by Kokusan Kagaku Co., Ltd.) was added and reacted by stirring at room temperature for 3 hours to obtain compound D (polysiloxane having a phosphorylcholine group) (see FIG. 5).

  A 10 wt% methanol solution of Compound D was applied to a 96-well plate made of polystyrene (Nihon BD). Next, after washing with methanol, it was dried to obtain a surface-treated well plate.

[Comparative Example 1]
A surface-treated well plate was obtained in the same manner as in Example 1 except that a 10 wt% methanol solution of the polysiloxane of Example 2 of Patent Document 4 was used.

[Protein adsorption experiment]
Proteins were adsorbed to the surface-treated well plates and untreated well plates of Examples 1 and 2 and Comparative Example 1, and the amount of protein adsorbed was quantified using the direct BCA method. The proteins used for the evaluation were albumin (Mw = 69000, pI = 4.9), γ-globulin (Mw = 150,000, 5.0 <pI <9.5), lysozyme (Mw = 14000, pI = 11.0). ) (Manufactured by Sigma).

  The experimental method will be specifically described below. First, each protein was mixed with a phosphate buffer (sodium chloride 8 mg / mL, potassium chloride 0.2 mg / mL, sodium monohydrogen phosphate 1.15 mg / mL, diphosphate 2 so that the concentration was 0.1 mg / mL. It was dissolved in potassium hydrogen 0.2 mg / mL, pH = 7.4) to obtain a protein solution. Next, 100 μl of the protein solution was placed in the well of the well plate and allowed to stand at 25 ° C. for 1 hour. Further, the wells were washed 5 times with 200 μl of phosphate buffer, and then 50 μl of PBS and 50 μl of BCA solution were added and allowed to stand at 60 ° C. for 1 hour for color development. Next, the absorbance of light with a wavelength of 562 nm was measured using a plate reader power scan HT (manufactured by Dainippon Sumitomo Pharma Co., Ltd.). When preparing a calibration curve, each protein solution 0, 2, 5, 10, 20, 40 μl was added to the well of the well plate, PBS was added to 50 μl, and BCA solution 50 μl was added. Measured the absorbance of light having a wavelength of 562 nm in the same manner as described above. The evaluation results are shown in FIG. From FIG. 6, it can be seen that any of albumin, γ-globulin and lysozyme can suppress the adsorption of protein to the well plate by surface treatment. Further, it can be seen that the surface-treated well plates of Examples 1 and 2 can suppress protein adsorption non-specifically than the surface-treated well plate of Comparative Example 1.

  The material modified by the surface modifier of the present invention is a material excellent in biocompatibility and hydrophilicity. Such materials can be applied to a wide range of uses such as cosmetics, artificial organs, medical materials such as surgical instruments, chromatographic fillers, affinity particles, and paints.

Claims (5)

General formula
Wherein R ¹ , R ² and R ³ are each independently an alkyl group having 1 to 6 carbon atoms, and R ⁴ is a hydrogen atom or an alkyl group having 1 to 18 carbon atoms. , X is an alkylene group having 1 to 18 carbon atoms, a polyoxyalkylene group or an arylene group having 1 to 18 units, Y is an amide bond, m is an integer of 2 to 6 .)
Polysiloxane and having a represented Ru configuration units in. A method for producing the polysiloxane according to claim 1 , comprising:
By oxidizing glycerophosphorylcholine , the chemical formula
A process for synthesizing a compound represented by the formula: A surface modifier comprising the polysiloxane according to claim 1 . A surface modification method comprising modifying a surface of a material using the surface modifier according to claim 3 .   A surface modifying material having a surface modified using the surface modifying agent according to claim 3.