JP4591926B2 - Material surface modification method - Google Patents

Description

  The present invention relates to a material surface modification method. The modification method of the present invention is applied to a wide variety of materials such as polymers, ceramics, metals, fibers, molding resins, and can easily provide molded products and raw materials having a surface excellent in biocompatibility and hydrophilicity, For example, it is useful as a medical material, a cosmetic compounding raw material, an analysis-related material, or a biochemical diagnostic material.

  Polymers having phosphorylcholine groups have been studied as biocompatible polymers, and biocompatible materials in which this polymer is coated on various bases have been developed.

For example, Patent Document 1 discloses a cosmetic material in which a powder coated with a homopolymer and a copolymer of 2-methacryloyloxyethyl phosphorylcholine is used as a cosmetic powder to improve moisture retention and skin adhesion. Has been.
Patent Documents 2 and 3 disclose medical materials and separating agents coated with a polymer having a phosphorylcholine group.

  The above materials have a phosphorylcholine structure by reacting mainly an acrylic monomer having a hydroxyl group with 2-chloro-1,3,2-dioxaphosphorane-2-oxide and further converting to quaternary ammonium with trimethylamine. The surface is coated with a polymer obtained by synthesizing and polymerizing the monomer (see Patent Documents 4 and 5 for the method for producing the polymer).

  In Patent Document 4, a copolymer of 2-methacryloyloxyethyl phosphorylcholine and methacrylic acid ester is produced, and in Patent Document 5, a homopolymer of 2-methacryloyloxyethyl phosphorylcholine is produced.

Patent Document 6 discloses surface treatment of a material with a phosphorylcholine group-containing compound having a reactive group as a method for improving biocompatibility by treatment with phosphorylcholine other than a polymer.
JP 7-118123 A JP 2000-279512 A JP 2002-98676 A JP-A-9-3132 JP-A-10-298240 Japanese National Patent Publication No. 5-505121

However, in the method of modifying the surface by coating the material with a polymer having a phosphorylcholine group, it is difficult to effectively coat the entire surface depending on the shape of the material. Moreover, since the coated polymer peels from the surface of the material, there may be a problem in durability. Furthermore, since the surface of the material is coated with a polymer, the basic properties required for the material itself may be lost, deviating from the purpose of imparting biocompatibility by the phosphorylcholine group.
In addition, the above production method of the polymer used for coating needs to be carried out under strict anhydrous conditions, and there is a problem that the technique is complicated. Furthermore, the stability of the phosphorylcholine group bonded to the coating polymer is also problematic due to the polymerization conditions.
Furthermore, the method disclosed in Patent Document 6 has a problem in stability due to the coupling mode, and the processing conditions are extremely limited and the processing efficiency is low, so that it is difficult to show an effect in practical use.

  From the above viewpoints, the present inventors have intensively studied the method of modifying the surface of various materials with phosphorylcholine groups. When a specific phosphorylcholine group-containing compound containing a group is reacted with a material surface having an arbitrary functional group that can be covalently bonded thereto via a carboxylic acid halide, a covalent bond forming reaction on the material surface facilitates the reaction. In addition, the present inventors have found that a phosphorylcholine group can be directly introduced onto the material surface with high versatility, and a material having excellent biocompatibility and hydrophilicity can be obtained, thereby completing the present invention.

  On the other hand, even when the material is coated with a polymer to modify the surface, when the method of the present invention is applied after coating with a specific polymer, it is physically simply cast by hydrophilic polymer. It has been found that the durability of the phosphorylcholine group on the surface of the material can be sufficiently ensured as compared with the conventional method which is merely coating. And depending on the material (a material having a certain thickness such as a substrate such as metal, plastic or glass or a processed product), the method of the present invention can be used while maintaining the basic properties required for the material. It became possible to impart hydrophilicity and biocompatibility very easily, and the present invention was completed by finding that it can be effectively used as a material for a separation analyzer and the like.

（１）
式中、Ｒ₁、Ｒ₂、Ｒ₃はそれぞれ独立に炭素原子数１〜６の直鎖若しくは分枝アルキル基を表す。Ｒ₄はカルボキシル基を表す。ｎ＝１〜１２、ｍ＝２〜４である。
That is, the present invention provides a phosphorylcholine group-containing compound represented by the following formula (1) obtained by introducing an amino group or a hydroxyl group on the surface of the material and then oxidative cleavage reaction of glycerophosphorylcholine with a carboxylic acid halide. And providing a method for modifying the surface of the material directly through covalent bonding to the surface of the material.

(1)
In the formula, R ₁ , R ₂ , and R ₃ each independently represent a linear or branched alkyl group having 1 to 6 carbon atoms. R ₄ represents a carboxyl group. n = 1-12 and m = 2-4.

  Furthermore, the present invention is characterized in that a phosphorylcholine group-containing compound of n = 1, m = 2 in the above formula (1) is directly introduced into the material surface via a covalent bond via a carboxylic acid halide. A method for surface modification of the above-mentioned material is provided.

（１）
式中、Ｒ₁、Ｒ₂、Ｒ₃はそれぞれ独立に炭素原子数１〜６の直鎖若しくは分枝アルキル基を表す。Ｒ₄はカルボキシル基を表す。ｎ＝１〜１２、ｍ＝２〜４である。 The present invention also provides a compound obtained by condensing a phosphorylcholine group-containing compound represented by the following formula (1) with a silane coupler having an amino group via a carboxylic acid halide, an amine having an olefin, or The present invention provides a method for modifying the surface of a material, which is introduced using a compound obtained by condensation with alcohol.

(1)
In the formula, R ₁ , R ₂ , and R ₃ each independently represent a linear or branched alkyl group having 1 to 6 carbon atoms. R ₄ represents a carboxyl group. n = 1-12 and m = 2-4.

By the method of the present invention, a phosphorylcholine group having excellent bond stability can be introduced on the surface of the material without losing the basic physical properties required for the material itself.
The phosphorylcholine group-modified material excellent in bond stability obtained by the method of the present invention effectively exhibits various effects attributable to the phosphorylcholine group.
In addition, we have developed a method of reacting an aldehyde obtained by oxidative cleavage of glycerophosphorylcholine with an amino group on the surface of the material (JP 2004-175676, JP 2004-225035). In some cases, after reaction, a secondary amine is formed at the junction between the phosphorylcholine group and the surface of the material, and it is positively charged in a certain pH range, so that negatively charged compounds may be adsorbed, resulting in undesirable effects. It was. Since the joint formed by this method is an amide or ester and is electrically neutral, the above problem can be avoided.

Hereinafter, the present invention will be described in detail.
The material whose surface is treated by the method of the present invention is not limited. For example, various materials made of polymer, ceramic or metal can be preferably processed. Preferred polymer materials to be processed include resin molded products, fibers, films, sheets, cloths, nonwoven fabrics, powders, etc., which are used as final products, intermediate processed products, raw materials, etc., and their shapes are limited Not. The same applies to materials made of ceramic or metal. Ceramic or metal workpieces, ceramic or metal powders are preferably treated.

合成ルート２

The compound of formula (1) may be a known compound or a novel compound. It can be produced by a known method. For example, it can be synthesized by the synthesis route shown below.





Synthesis route 1

Synthesis route 2

（２）
式中、Ｒ₁、Ｒ₂、Ｒ₃はそれぞれ独立に炭素原子数１〜６の直鎖若しくは分枝アルキル基を表す。ｎ＝１〜１２、ｍ＝２〜４である。 In general, a compound having a carboxyl group can be directly covalently bonded to the surface of a material having an amino group or a hydroxyl group. However, as shown in the following formula (2), the phosphorylcholine-containing compound of the formula (1) having a carboxyl group at the terminal is extremely highly polar, particularly when n = 1 to 6, and is soluble only in water or methanol. In addition, a condensing agent such as carbodiimide or carbonyldiimidazole cannot be used, and it is not suitable for esterification reaction. In addition, since amidation also has limited coupling agents that can be reacted in water, there are problems such as poor reaction variations and inability to use when the partner compound to be coupled reacts with water. On the other hand, in the case of a method through activation using thionyl chloride, phosphorus pentachloride, phosphorus oxychloride, phosphorus tribromide, oxalyl chloride, and the like and via a carboxylic acid halide, the carboxylic acid halide of the phosphorylcholine compound is organic. It has been found that it is also soluble in a solvent, and esterification and amidation proceed without problems and can be condensed with a compound that reacts with water. In addition, the reagent which produces | generates a carboxylic acid halide is not limited to the above, Other reagents can also be used as needed.

(2)
In the formula, R ₁ , R ₂ , and R ₃ each independently represent a linear or branched alkyl group having 1 to 6 carbon atoms. n = 1-12 and m = 2-4.

  N of the compound represented by the formula (2) is defined as described above, and n is preferably as small as possible. In the case of 1, when the phosphorylcholine group is closest to the treatment surface, the protein adhesion inhibitory effect is maximized. The

The direct introduction of the phosphorylcholine group-containing compound of the formula (2) may include an optional spacer between the compound of the formula (2) and the functional group on the material surface, such as a silane coupling agent. .
Further, it means that a method of coating the material with a polymer in which the phosphorylcholine group-containing compound of the formula (2) is covalently bonded is not included.
The material itself is already coated with a polymer having a functional group capable of reacting with the compound of the formula (2) or such a material, and the compound of the formula (2) is shared with them. The method of combining is not excluded from the method of the present invention.

The surface of the material to be modified must have a functional group (amino group, hydroxyl group, etc.) that can be covalently bonded to the compound of the formula (2).
When there are no amino groups, hydroxyl groups, or functional groups (silanol groups, hydrosilyl groups, etc.) that react with the silane coupling agent in the material itself, these are introduced by a known method or a method developed in the future. For example, an amino group, a hydroxyl group, or a silanol group can be imparted to the material surface by a known method shown below.

1. Introduction of amino groups by surface reaction of plasma treatment Amino groups are introduced to the material surface by low temperature plasma under nitrogen gas atmosphere. Specifically, the raw material is housed in a plasma reaction vessel, the inside of the reaction vessel is evacuated with a vacuum pump, and then nitrogen gas is introduced. Subsequently, an amino group can be introduced on the surface of the material by glow discharge. For example, fluororesin, various metals (stainless steel, titanium alloy, aluminum, iron, etc.), ceramics, carbon-based materials, various polymers (urethane, polycarbonate, polyimide, acrylic, vinyl, polysaccharide, polyalkylsiloxane), organic- Amino groups are preferably introduced into materials such as inorganic composite materials and various inorganic materials (mica, talc, kaolin, alumina, titanium oxide, zinc oxide, iron oxide, various inorganic pigments).
According to this method, a material in which the amino group is directly bonded to the material surface can be obtained without the material surface being coated with a substance such as a polymer to be combined. Therefore, the function of the material itself is not impaired except for introducing a phosphorylcholine group.

2. Introduction of amino groups by plasma polymerization Radicals are generated on the material surface by plasma treatment. Subsequently, it is treated with a monomer and polymerized to introduce an amino group. For example, a polylactic acid film is accommodated in a plasma reaction vessel, the inside of the vessel is evacuated, and radicals are generated on the film surface by discharge. Subsequently, the film is taken out from the container, immersed in a THF (tetrahydrofuran) solution of nitrogen-substituted allylamine, and subjected to graft polymerization.
An amine monomer can be used as the monomer for treating the material. The amine monomer is not limited to allylamine, and may have an amino group and a reactive site such as polymerizable vinyl or acrylic. The amino group may be protected by a butoxycarbonyl group, a benzyloxycarbonyl group or the like.
Moreover, even if it is not an amine-type monomer, the monomer which has a functional group which can introduce | transduce an amino group easily by reaction with diamine like an epoxy group may be sufficient, for example.

3. Introduction of hydroxyl groups by surface reaction of plasma treatment Hydroxyl groups are introduced to the material surface by low temperature plasma in an oxygen gas atmosphere. Specifically, the raw material is housed in a plasma reaction vessel, the inside of the reaction vessel is evacuated with a vacuum pump, and oxygen gas is then introduced. Subsequently, hydroxyl groups can be introduced on the surface of the material by glow discharge. For example, fluororesin, various metals (stainless steel, titanium alloy, aluminum, iron, etc.), ceramics, carbon-based materials, various polymers (urethane, polycarbonate, polyimide, acrylic, vinyl, polysaccharide, polyalkylsiloxane), organic- Hydroxyl groups are preferably introduced into materials such as inorganic composite materials and various inorganic materials (mica, talc, kaolin, alumina, titanium oxide, zinc oxide, iron oxide, various inorganic pigments).
According to this method, a material in which a hydroxyl group is directly bonded to the material surface can be obtained without the material surface being coated with a substance such as a polymer to be combined. Therefore, the function of the material itself is not impaired except for introducing a phosphorylcholine group.

The literature regarding plasma processing is shown below.
1. M. Muller, C. oehr
Plasma aminofunctionalisation of PVDF microfiltration membranes: comparison of the in plasma modifications with a grafting method using ESCA and an amino-selective fluorescent probe
Surface and Coatings Technology 116-119 (1999) 802-807
2. Lidija Tusek, Mirko Nitschke, Carsten Werner, Karin Stana-Kleinschek, Volker Ribitsch
Surface characterization of NH3 plasma treated polyamide 6 foils
Colloids and Surfaces A: Physicochem. Eng. Aspects 195 (2001) 81-95
3. Fabienne Poncin-Epaillard, Jean-Claude Brosse, Thierry Falher
Reactivity of surface groups formed onto a plasma treated poly (propylene) film
Macromol. Chem. Phys. 200. 989-996 (1999)

4). Introduction of amino group by surface modifier The surface of silanol-containing powder, titanium oxide powder or the like is treated using a surface modifier such as alkoxysilane, chlorosilane, or silazane having an amino group.
For example, an amino group is introduced by treating silica powder with 3-aminopropyltrimethoxysilane having a primary amino group. Specifically, silica is immersed in a water-2-propanol mixed solution, and 3-aminopropyltrimethoxysilane is added, followed by heating to 100 ° C. and reaction for 6 hours. After cooling to room temperature, the silica is washed with methanol and dried to obtain a powder in which amino groups are directly introduced on the silica surface. In addition to silica, materials that are preferably treated in this method include molded products and powders such as glass, alumina, talc, clay, aluminum, iron, mica, asbestos, titanium oxide, zinc white, and iron oxide.
According to this method, a material in which an amino group is directly bonded to a functional group on the material surface can be obtained without the material surface being coated with a substance such as a polymer to be combined. Therefore, the function of the material itself is not impaired except for introducing a phosphorylcholine group.

5). Introduction of amino groups by silicon gas phase treatment (see Japanese Patent Publication No. 1-54379, Japanese Patent Publication No. 1-54380, Japanese Patent Publication No. 1-54381)
The powder surface is first treated with 1.3.5.7-tetramethylcyclotetrasiloxane, and Si-H groups introduced on the surface are reacted with monomers having amino groups to obtain an aminated surface. . For example, mica and 1.3.5.7-tetramethylcyclotetrasiloxane are placed in a desiccator and deaerated with an aspirator. After reacting at 80 ° C. for 16 hours, the mica is taken out and dried at 120 ° C. The obtained mica is dispersed in ethanol, allylamine is added, and then an ethanol solution of chloroplatinic acid is added, followed by stirring at 60 ° C. for 2 hours. After completion of the reaction, filtration, washing with ethanol and drying under reduced pressure give aminated mica. Preferred powders that can be treated by this method include fluororesins, various metals (stainless steel, titanium alloy, aluminum, iron, etc.), ceramics, carbon-based materials, and various polymers (urethane, polycarbonate, polyimide, acrylic, vinyl, many Examples thereof include powders such as sugars, polyalkylsiloxanes), organic-inorganic composite materials, and various inorganic substances (mica, talc, kaolin, alumina, titanium oxide, zinc oxide, iron oxide, various inorganic pigments).
As the monomer used in this method, an amine monomer can be used. The amine monomer is not limited to allylamine, and may have an amino group and a reactive site such as polymerizable vinyl or acrylic. The amino group may be protected by a butoxycarbonyl group, a benzyloxycarbonyl group or the like.
Moreover, even if it is not an amine-type monomer, the monomer which has a functional group which can introduce | transduce an amino group easily by reaction with diamine like an epoxy group may be sufficient, for example.

"Production method of surface modifier and method of surface modification of material using this surface modifier"
Next, the invention described in claim 4 will be described. The surface modifier is obtained by the production method shown below, and is used to modify a material having a silanol group.

A: Method for producing compound (surface modifier) by condensation reaction with silane coupler having amino group A silane coupler such as alkoxysilane, chlorosilane, silazane etc. having amino group and phosphorylcholine group-containing compound of formula (2) A surface modifier having a phosphorylcholine group can be synthesized by condensation via an acid halide. For example, 3-aminopropyltrimethoxysilane having a primary amino group and the carboxyl form of compound (2) can be condensed by an amide bond. Specifically, the carboxyl form of compound (2) is dispersed in acetonitrile, and thionyl chloride is added to obtain a carboxylic acid halide. In addition to this reagent, phosphorus pentachloride, phosphorus oxychloride, phosphorus tribromide, oxalyl chloride and the like may be used. 3-Aminopropyltrimethoxysilane is added to this solution and then allowed to react at room temperature for 3 hours. The solution is concentrated under reduced pressure and dried to obtain the desired surface modifier. Examples of the surface modifier that can be preferably synthesized by this method include various silane coupling agents having a hydroxyl group, a carboxyl group, and an amino group.

B: Method for producing compound (surface modifier) by condensation reaction with amine or alcohol having olefin Through amine or alcohol having double bond and phosphorylcholine group-containing compound of formula (2) via carboxylic acid halide Then, it is condensed by amidation or esterification, and a hydrosilyl compound such as trichlorosilane is reacted with a double bond using a platinum catalyst to introduce a silyl group, thereby synthesizing a target silane coupler. The compound having a double bond may be a compound having a longer alkyl chain in addition to vinylamine, vinyl alcohol, allylamine, and allyl alcohol. The platinum catalyst is preferably chloroplatinic acid, but is not limited thereto.

  By treating the silane coupler surface modifier obtained above with a material having a silanol group according to a conventional method, the phosphorylcholine group-containing compound of the formula (2) is directly introduced into the material surface by a covalent bond.

  Hereinafter, the present invention will be described in more detail with reference to examples. The present invention is not limited to the following examples. The phosphorylcholine group introduced on the surface of the material can be quantified by confirming with FT-IR and elemental analysis.

“Synthesis Example 1”
In a 200 ml flask, add 5 g of glycerophosphorylcholine, 17 g of sodium periodate, 81 mg of ruthenium trichloride nhydrate, 70 g of ion-exchanged water, and 30 g of acetonitrile. After stirring at room temperature for 2 hours, the mixture was filtered and the solvent was removed from the filtrate. The target compound (3) was obtained by extracting the target compound with methanol from the obtained solid and subsequently removing the methanol. The reaction yield was almost 100%.

FIG. 4 shows the ¹ H NMR spectrum, and FIG. 5 shows the Mass spectrum. This shows that the target compound of formula (3) is produced.

（３）

（４） “Synthesis Example 2”
As a phosphorylcholine group-containing compound of the formula (2), 7.0 g of the compound of the following formula (3) was dispersed in 30 ml of N, N-dimethylformamide, 10 g of thionyl chloride was added under ice cooling, and the mixture was stirred for 30 minutes. 3.5 g of 3-aminopropyltrimethoxysilane was added, and the mixture was stirred and reacted for 4 hours to obtain a mixed solution containing a compound of the following formula (4).

(3)

(4)

（５） “Synthesis Example 3”
7.0 g of the phosphorylcholine group-containing compound of the formula (3) was dispersed in 30 ml of anhydrous acetonitrile, and 10 g of thionyl chloride was added under ice cooling and reacted for 5 hours. After adding 2 g of triethylamine and 1.7 g of allyl alcohol and stirring at room temperature for 3 hours, the solvent was distilled off under reduced pressure. The residue is purified by column chromatography, dissolved in anhydrous acetonitrile, 0.01 g of chloroplatinic acid and 5 g of trichlorosilane are added, and the mixture is heated and stirred at 70 ° C. for 5 hours, followed by addition of 5 g of methanol. Compound (5) was obtained.

(5)

（４） “Synthesis Example 4”
7.0 g of the phosphorylcholine group-containing compound of the formula (3) was dispersed in 30 ml of anhydrous acetonitrile, and 10 g of thionyl chloride was added under ice cooling and reacted for 5 hours. After adding 2 g of triethylamine and 1.6 g of allylamine and stirring at room temperature for 3 hours, the solvent was distilled off under reduced pressure. The residue is purified by column chromatography, dissolved in anhydrous acetonitrile, 0.01 g of chloroplatinic acid and 5 g of trichlorosilane are added, and the mixture is heated and stirred at 70 ° C. for 5 hours, followed by addition of 5 g of methanol. Compound (4) was obtained.

(4)

（５） “Synthesis Example 5”
As a phosphorylcholine group-containing compound of the formula (1), 7.0 g of the compound of the above formula (3) was dispersed in 30 ml of N, N-dimethylformamide, 12 g of oxalyl chloride was added under ice cooling, and the mixture was stirred for 30 minutes. 3.5 g of 3-aminopropyltrimethoxysilane was added, and the mixture was stirred and reacted for 4 hours to obtain a mixed solution containing a compound of the following formula (5).
“FIG. 7” shows the NMR data of the compound of the formula (5).

(5)

“Comparative Synthesis Example 1”
Synthesis route 2 shows a synthesis scheme of compound (e).

“Comparative Synthesis Example 2”
As a phosphorylcholine group-containing compound of the formula (1), 7.0 g of the compound of the above formula (3) is dispersed in 30 ml of water, 5.2 g of N-hydroxysuccinimide, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride When 6.5 g of salt and 3.5 g of 3-aminopropyltrimethoxysilane were added and stirred and reacted for 4 hours, the condensation reaction of trimethoxysilane proceeded and the desired compound (4) was obtained with high purity. I couldn't.

“Comparative Synthesis Example 3”
As a phosphorylcholine group-containing compound of the formula (1), 7.0 g of the compound of the above formula (3) is dispersed in 30 ml of methanol, 5.2 g of N-hydroxysuccinimide, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride When 6.5 g of salt and 3.5 g of 3-aminopropyltrimethoxysilane were added and stirred and reacted for 4 hours, the condensation reaction with methanol was inhibited, and the desired compound (4) was obtained with high purity. could not.

Example 1
A quartz plate (1 cm × 1 cm, thickness 1 mm), which is a material to be surface-modified, is immersed in a mixed solution of 1 ml of a mixture containing the compound of the formula (5) in Synthesis Example 2 (10% of the actual amount), 1 ml of water, and 5 ml of methanol. After standing at room temperature for 2 hours, it was dried overnight. Thereby, the compound of the formula (4) was directly introduced into the surface of the quartz material by a covalent bond.
This was immersed in 5 ml of 5-mmol solution of 2- (N-morpholino) ethanesulfonic acid buffer (pH 5) of bovine serum albumin (BSA) 5 mg / ml, and allowed to stand overnight, and then the BSA concentration in the supernatant was absorbed by UV absorption (λ = 280 nm). ). The results are shown in “FIG. 1”. As a control, a similar experiment was performed using an untreated quartz plate (Comparative Example 1) into which the compound of formula (5) was not introduced.
The quartz plate modified by the method of the present invention has an extremely low BSA adsorption amount.

"Example 2"
40 mg of the compound of formula (3) was added to anhydrous DMF, 40 mg of thionyl chloride was added and stirred for 30 minutes. Cross-linked polyvinyl alcohol (16 mmφ) was immersed and reacted for 4 hours, and then thoroughly washed with water to obtain a cross-linked polyvinyl alcohol material treated with phosphorylcholine. This was immersed in 5 ml of a 5-mmol solution of lysozyme 5 mg / ml 2- (N-morpholino) ethanesulfonic acid buffer (pH 5), allowed to stand overnight, and then the BSA concentration in the supernatant was quantified by UV absorption (λ = 280 nm). The results are shown in “FIG. 5”. As a control, the same experiment was performed for the compound (e) synthesized in Comparative Synthesis Example 1.
The same experiment was conducted using untreated crosslinked polyvinyl alcohol (Comparative Example 2) into which the compound of formula (5) was not introduced. Although the protein adsorption was reduced by the introduction of the phosphorylcholine group, the effect was better in (3) where n is 1 than in (e) where n is 6.

"Example 3"
A glass plate (1 cm × 1 cm, thickness 0.5 mm) was immersed in 50 ml of methanol / water = 90/10 solution of 20 mg of 3-aminopropyltrimethoxysilane at 50 ° C. for 3 hours. The treated glass plate was thoroughly washed with methanol and dried. Add 30 mg of the compound of chemical formula (3) to anhydrous DMF, add 30 mg of thionyl chloride and stir for 30 minutes, add 0.5 ml of triethylamine and the above glass plate, and leave it at room temperature overnight to form a glass plate treated with phosphorylcholine. Obtained. This was immersed in 5 ml of 5-mmol solution of 2- (N-morpholino) ethanesulfonic acid buffer (pH 5) of bovine serum albumin (BSA) 5 mg / ml, and allowed to stand overnight. ). The results are shown in “FIG. 6”. As a control, a similar experiment was performed using an untreated quartz plate (Comparative Example 3) into which the compound of formula (6) was not introduced.
The quartz plate modified by the method of the present invention has a remarkably low albumin adsorption amount.

  The modification method of the present invention is applied to a wide variety of materials such as polymers, ceramics, metals and fibers, and can easily provide molded products and raw materials having a surface excellent in biocompatibility and hydrophilicity. It is useful as a material, cosmetic blending raw material, chromatographic filler and the like. Moreover, it is useful for modifying members such as a separation analyzer.

4 is a graph comparing the amount of BSA adsorption of Example 1. It is 1H-NMR of the compound of Formula (e). It is 1H-NMR of the compound of Formula (3). It is a MASS spectrum of a compound of a formula (3). 4 is a graph for comparing lysozyme adsorption amounts of Example 2. It is a graph which compares the albumin adsorption amount of Example 3. It is 1H-NMR of the compound of Formula (4).

Claims (3)

A phosphorylcholine group-containing compound represented by the following formula (1) obtained by introducing an amino group or a hydroxyl group into the material surface and then oxidative cleavage reaction of glycerophosphorylcholine is introduced into the material surface via a carboxylic acid halide. A method for modifying the surface of a material, comprising the step of directly introducing by covalent bonding.
(1)

In the formula, R ₁ , R ₂ , and R ₃ each independently represent a linear or branched alkyl group having 1 to 6 carbon atoms. R ₄ represents a carboxyl group. n = 1-12 and m = 2-4. 2. The phosphorylcholine group-containing compound of n = 1, m = 2 in the formula (1) is introduced by covalent bond directly to the material surface via a carboxylic acid halide. Material surface modification method. Obtained by condensing a phosphorylcholine group-containing compound represented by the following formula (1) via a carboxylic acid halide with a silane coupler having an amino group, or an amine or alcohol having an olefin. A method for modifying the surface of a material, characterized in that it is introduced using a compound that can be obtained .

(1)
In the formula, R ₁ , R ₂ , and R ₃ each independently represent a linear or branched alkyl group having 1 to 6 carbon atoms. R ₄ represents a carboxyl group. n = 1-12 and m = 2-4.

Images