JP2573936B2 - Modified solid material - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a modified solid material having on its surface a silicone polymer film having at least one functional moiety. In particular, the present invention relates to a method of coating a solid material, preferably on substantially the entire surface, first with a coating of a particular silicone polymer, subsequently attaching a spacer compound to the silicone polymer and further chemically modifying the spacer groups thus introduced. By chemically modifying the acceptor moiety and introducing a functional moiety, the surface activity of the solid material is lost, avoiding the generation of hydrogen from the surface by coexisting water or alcohol,
Furthermore, the present invention relates to a modified solid material which can be imparted with various functions (filler for liquid chromatography, carrier for immobilized enzyme, etc.) by appropriately selecting a functional portion.

The solid material targeted by the present invention is not limited in size, shape and material as long as it is solid at normal temperature. Therefore,
From ultrafine powder of about 0.02 μm to powder on the order of mm, and objects of the order of cm to m or larger. The shape of the solid material of the present invention includes powder, fiber, sheet, and lump. Furthermore, porous materials, tubes, sponges, films, coatings,
It can be beads, flakes, and the like. In addition, an aggregate, a molded body or a shaped body, or a composite body of one or more materials is also included. The material is also arbitrary. For example, inorganic materials (for example, metals and derivatives thereof (for example, metal oxides), minerals, ceramics, concrete, and glass) and organic materials (for example, biological substances (biopolymers such as wood and cellulose, small biomolecules and the like), Synthetic substances, organic pigments, etc.].

The solid material of the present invention is, for example, a fluid permeable material (for example, a monolithic carrier or a porous body). The fluid permeable material is made of, for example, ceramics (eg, activated alumina, cordierite, etc.), metal (alumina alloy, iron, stainless steel, etc.), biopolymer (cellulose, chitin, etc.), carbon or glass. The fluid permeable material is usually
A large number of transmission ports having a diameter of 0.001 to 1000 μm, preferably 0.01 to 300 μm, and more preferably 0.01 to 10 μm are provided. The shape is generally sheet-like, cylindrical or plate-like.

The solid material of the present invention includes a powder. In the present specification, “powder” means from about 0.02 μm (ultra fine powder) to 10 mm
Means a degree object.

Many aspects of the solid material of the present invention can be considered in addition to the fluid permeable material and the powder. Hereinafter, the present invention will be described mainly along a powder (in some cases, a fluid-permeable material), but this is for convenience of description and does not limit the present invention.

The modified powder according to the present invention does not modify or decompose the fragrance, oil or resin coexisting therewith. Therefore, without causing problems such as deterioration, odor and discoloration, for example, cosmetics,
Pharmaceuticals, resin compositions, paints, inks, paints, ornaments,
It can be used in the fields of fragrances, magnetic materials, immobilized enzymes, packing materials for liquid chromatography and medical materials. Furthermore, since the Si-H portion contained in the silicone polymer film that coats the powder is substantially eliminated or greatly reduced, it can be effectively incorporated in, for example, an emulsification system. In addition, a composite material having various functions can be provided.

[Conventional technology]

When introducing a functional group into the powder, a silane coupling agent is generally used. For example, silica can be easily treated with a silane coupling agent. However, there are some such as zinc white and titanium dioxide which are difficult to treat with a silane coupling agent. Further, when a silane coupling agent is introduced into, for example, a metal oxide, the OH group present on the surface of the metal oxide is reacted with the silane coupling agent. Therefore, the functional group introduced by the silane coupling agent cannot bind firmly to the metal oxide.
Further, when treated with a silane coupling agent, it is not possible to obtain a silicone polymer covering substantially the entire surface of the metal oxide. Therefore, the metal atoms of the metal oxide are exposed on the surface, and the surface activity cannot be sufficiently blocked.
Therefore, when the metal oxide treated with the silane coupling agent is mixed with, for example, a cosmetic, it may cause a problem such as deterioration or odor. Furthermore, the dispersibility cannot be controlled, though it has some hydrophobicity.

The present inventors have found the following means for solving the above-mentioned drawbacks, and have described such means in a separately filed Japanese Patent Application No. 61-178269, “Modified powder”. That is, the above-mentioned disadvantages can be solved by a modified powder obtained by coating the powder surface with a silicone polymer film having a Si-H portion and further adding a pendant group to the Si-H portion.

The process of adding a pendant group after coating with a silicone polymer has improved properties (eg, hydrophobicity, stability) while maintaining the original properties of the powder, and also enhances the surface activity of the powder. It is advantageous in that it gives up a modified powder which can be eliminated (ie, does not cause the alteration or decomposition of the other co-existing components) and can be incorporated, for example, into an emulsified system.

[Problems to be solved by the invention]

However, some compounds for introducing pendant groups are very expensive, and pendant groups containing acidic or basic functional groups may inhibit the addition reaction because they hydrolyze the Si-H portion of the silicone polymer. That the addition reaction of the pendant group having a low boiling point may be carried out in a pressurized system, and that the addition of the pendant group having a high polymerizability may cause a part of the modified powder to aggregate strongly.
There were also points where further improvement was desired.

It is therefore an object of the present invention not only to overcome the disadvantages of the prior art, but also to provide an improvement of the invention by the present inventors. That is, an object of the present invention is to maintain the original properties of a solid material such as a powder, to have sufficiently improved properties, and to eliminate the surface activity of the solid material such as a powder, It is an object of the present invention to provide a modified solid material which can be produced by a method which is advantageous to the present invention.

[Means for solving the problem]

According to the present invention, (a) a solid material having a silicone polymer film having a weight average molecular weight of 200,000 or more and containing at least one reactive moiety which is a Si-H moiety or a derivative thereof is prepared on the surface, b) treating the solid material of step (a) with a spacer compound having at least one Si-bonding moiety and at least one chemically modified accepting moiety capable of reacting with the reactive moiety and bonding to the Si atom. Reacting the reactive moiety with the Si-bonding moiety in a solid-liquid reaction to bind the spacer compound to the silicone polymer film, and (c) chemically modifying the chemically modified accepting moiety to form a functional moiety. There is provided a modified solid material having a silicone polymer film having a functional part, which is introduced thereon, supported on the surface.

In the present invention, the surface of the solid material is modified by sequentially treating any solid material in the steps (a) to (c). First, in the first step (the step (a)), a silicone polymer film is formed on the solid material, preferably on substantially the entire surface, by any method. At that time, it is necessary to prepare a reactive portion (that is, a portion capable of reacting with the Si-bonding portion of the spacer compound used in the second step) on the silicone polymer film.

Subsequently, in a second step (the step (b)), a Si-bonding part corresponding to the reactive part on the silicone polymer film prepared in the first step is suitable for the chemical modification intended in the third step. A spacer compound having a chemically modified acceptor moiety is selected, bonded to the silicone polymer film, and a spacer group, which is a residue of the spacer compound, is introduced onto the silicone polymer film.

Further, in the third step “Step (c)], the chemically modified accepting moiety present in the spacer group is chemically modified,
A modified solid material having any desired function is obtained.

 Hereinafter, the present invention will be described in detail.

The powder modified in the present invention is not particularly limited. Representative examples of such powders include inorganic pigments, metal oxides, metal hydroxides, organic pigments, pearlescent materials, silicate minerals, porous materials, carbon, metals, biopolymers, mica and composite powders Is included. These powders may be processed by one type or by combining a plurality of types. Furthermore,
One or more agglomerates, compacts or shaped bodies of these powders can also be treated. In addition, the powders treated in the present invention may contain other substances on or in them (eg, colorants, UV absorbers, pharmaceuticals, various additives).

In the first stage of the modification according to the invention, the powder is coated with a film of a silicone polymer having at least one reactive moiety.

In the present specification, the “reactive portion” on the silicone polymer film comprises a Si—H portion or a derivative portion thereof. The derivative portion of Si-H includes, for example, a Si-OH portion generated by hydrolyzing Si-H or a Si-halogen portion generated by further halogenating the Si-OH portion.

In the first coating step, any silicone compound can be used as long as a silicone polymer film having at least one reactive moiety can be formed on the powder surface.

In the first stage coating step, a silicone compound having at least one Si-H moiety can be used,
Preferably a general formula (Wherein, R ¹ , R ² and R ³ are each independently a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms which may be substituted with at least one halogen atom. ,
R ¹ , R ² and R ³ are not simultaneously hydrogen atoms, and R ⁴ , R ⁵ and R ⁶ are each independently a hydrogen atom or substituted by at least one halogen atom. A hydrocarbon group having 1 to 10 carbon atoms, and a is 0
Or an integer of 1 or more, b is 0 or an integer of 1 or more, and c is 0 or 2, provided that when c is 0, the sum of a and b is an integer of 3 or more. And the maximum value of a + b + c should be 10,000). In the formula (I), the groups R ^{1 to} R ⁶ may be different from each other in each repeating unit.

The silicone compounds of the formula (I) consist of two groups. The first group corresponds to the case where c = 0 in the above formula (I), and has a general formula (R ¹ HSiO) _a (R ² R ³ SiO) _b (III) wherein R ¹ , R ² , R ³ , a and b have the same meanings as described above, but preferably R ¹ , R ² and R ³ are each independently a lower alkyl having 1 to 4 carbon atoms which may be substituted with at least one halogen atom. An alkyl group or an aryl group (for example, a phenyl group), and the sum of a and b is 3 or more.]

The second group of the silicone compounds of the formula (I) corresponds to the case where c = 2 in the formula (I), [In the formula, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , a and b have the same meaning as described above, and c is 2, but preferably R ^{1 to} R ⁶ are each independently carbon A lower alkyl group or an aryl group (e.g., a phenyl group) of 1 to 4].

The first coating step of the modification according to the present invention can be carried out by various methods (including conventional coating methods).

For example, a high-molecular silicone compound is dissolved in an organic solvent (eg, chloroform, hexane, benzene, toluene, acetone), a powder is dispersed therein to prepare a dispersion, and the dispersion is heated to remove the solvent. The powder can be coated with a silicone polymer coating by evaporating to form a coating on the powder surface. Further, a film can be formed by drying the above-mentioned dispersion liquid with a spray drier. Alternatively, by pouring the dispersion into the poor solvent of the high-molecular silicone compound, or by pouring the poor solvent into the dispersion and adhering the insolubilized silicone compound on the powder surface to form a film thereof. Powder coating can be performed.

The coating treatment can also be performed by mechanochemically treating the liquid polymer silicone compound and the powder in a ball mill, for example.

Further, as in an in situ polymerization method, the powder can be encapsulated with a silicone polymer film by polymerizing the silicone compound monomer on the surface of the powder in the presence of a catalyst.

Alternatively, the first coating step of the modification according to the invention can be carried out using active sites which are widely distributed over substantially the entire surface of the powder to be modified. As used herein, the term “active site” refers to a site capable of catalyzing the polymerization of a silicone compound having a siloxane bond (Si—O—Si) or Si—H (hydrosilyl) group. , An oxidation point or a reduction point.

In the coating step utilizing active sites, the silicone compound is brought into contact with the above-mentioned various powders in the form of its own vapor, in the form of a solution dissolved in an appropriate solvent, or in its own liquid form, It can be polymerized on the surface of the body.

A process in which a liquid silicone compound itself comes into direct contact with powder (hereinafter sometimes referred to as a liquid phase process).
Is a suitable mixer such as a rotary ball mill, a vibrating ball mill, a planetary ball mill, a sand mill, an attritor,
This is carried out by charging the powder into a pug mill, poni mixer, planetary mixer, crusher, or the like, and processing the powder mechanochemically. Care should be taken in this liquid phase treatment because the shape of the powder may change. Preferred powders for use in this liquid phase treatment are, for example, talc, mica or a mixture of spherical resins (eg, nylon, polyethylene, cellulose) and fine powders (eg, pigments). When the mixture is treated with the silicone compound while mixing the talc, mica or spherical resin with the pigment, the talc, mica or spherical resin as a core is coated with the pigment and the silicone resin.

As another method of the liquid phase treatment, a solution of the silicone compound and a powder may be brought into contact. As a solvent for the silicone compound, an organic solvent such as chloroform or hexane can be used. Preparing a solution containing 1 to 50% by weight of the silicone compound in the solvent,
Dispersing the powder therein, followed by heating to evaporate the solvent and polymerize the silicone compound on the surface,
Alternatively, the above solution can be directly sprayed on the powder, and subsequently heated to evaporate the solvent to polymerize the silicone compound.

Powders that can be used in this liquid phase treatment are powders that can be easily filtered, such as talc and mica. Further, a silicone compound suitable for the liquid phase treatment is, for example, a compound in which a + b + c in the formula (I) is 10,000 or less.

The silicone compound may be brought into contact with powder in the form of vapor (hereinafter, may be referred to as a gas phase treatment).
Specifically, the basic mode of the gas phase treatment is as follows. A powder and a silicone compound (for example, a cyclic organosiloxane) are put in separate containers in a closed room (for example, at 100 ° C. or lower) and the upper part is opened. Just do it. In this state, the silicone compound is vaporized by the partial pressure at that temperature and maintains adsorption equilibrium on the powder. When the treated powder is removed from the sealed room, if the powder is not active, the silicone compound will desorb and the powder will return to the original surface. In the case of a powder having the following formula, the silicone compound is polymerized on the powder because of the polymerization activity, and the partial pressure of the silicone compound on the powder surface is reduced, so that the silicone compound in the container is vaporized and supplied. Since the surface polymerization occurs in such an order, the silicone compound is supplied in a required amount in the system, and there is no waste. Since gas-phase processing is based on such a simple principle, no special equipment is required. For example, any closed room (eg, a closed room that can be kept at a constant temperature) such as a gas sterilizer or a constant temperature bath can be used. In addition, a desiccator can be used for the small amount treatment. However, ideally, a device capable of degassing after treatment is desirable, and a gas sterilization device is preferably used. Continuous or intermittent agitation of the powder in the closed room can make contact between the powder and the silicone compound vapor desirable.

According to another embodiment of the gas phase treatment, at 120 ° C. or lower, preferably 1 ° C.
Only the powder is previously charged into a closed room at a temperature of 00 ° C. or less, and the silicone compound is vaporized at a predetermined partial pressure in another closed room at a temperature of 120 ° C. or less, and the powder is charged. The vaporized silicone compound can be introduced into the room by, for example, a pipe. Although there is no particular limitation on the pressure of the system, the polymerization is 200 mmHg or less, preferably 100 mmHg.
It is preferably carried out under the following pressure. In either embodiment, the treatment time is from 30 minutes to 150 hours, after which the unpolymerized silicone compound is removed by degassing,
Obtain the desired product.

According to another embodiment of the gas phase treatment, the powder can be treated by contacting the silicone compound in the form of a gas mixture with a carrier gas (for example by supplying to the powder surface). The mixing of the silicone compound with the carrier gas is accomplished by, for example, heating the silicone compound, if necessary, until the silicone compound has a vapor pressure of at least 1 mmHg, preferably at least 100 mmHg, and then flowing the carrier gas into or at the surface of the silicone compound. It can be implemented by being introduced above. The supply rate of the carrier gas stream can be appropriately determined depending on, for example, the vapor pressure of the silicone compound, the type and amount of the powder, and the capacity of the processing container. It is preferably prepared so that the treatment can be performed in 30 minutes to 150 hours.

As the carrier gas, an inert gas such as nitrogen, argon, helium, or the like is preferable, but a mixed gas in which water, methanol vapor, or ethanol vapor is mixed with air or the inert gas in a gas molecule state can also be used.

According to the gas phase treatment, the mixed gas containing the silicone compound is brought into contact with the powder to be modified. Since the mixed gas contains a silicone compound as saturated vapor,
It is necessary that the reaction temperature be equal to or higher than the temperature of the gas mixture. If the contact / reaction temperature is lower than the temperature of the mixed gas, the silicone compound is condensed and the powder is easily treated in an agglomerated form. When a powder having many strong active sites on the surface is treated with the mixed gas, the powder is easily slurried. In this case, it is preferable that the contact / reaction temperature be equal to or higher than the temperature of the supplied mixed gas and that a carrier gas containing no silicone compound is simultaneously supplied to reduce the relative pressure of the silicone compound with respect to the saturated vapor pressure.

The silicone compound and the carrier gas can be separately introduced and mixed in the reaction vessel.

As described above, in the gas phase treatment, by supplying a mixed gas of a silicone compound and a carrier gas to the powder surface, molecules of the silicone compound are continuously adsorbed to the powder, and active points on the surface are utilized. And polymerization.

The above-mentioned gas-phase treatment can be advantageously performed on all powders targeted by the present invention. In particular, it is preferable to use a gas phase treatment for ultrafine powders, porous materials, pearl pigments, organic pigments, and the like. When these powders are processed by gas phase processing, an ultra-thin silicone polymer film is formed,
Porosity, pearl effect, etc. can be maintained. Also,
By subjecting a metal that is easily oxidized to a gas phase treatment immediately after its generation, a metal powder that is stable against oxidation can be obtained. Suitable silicone compounds for the gas phase treatment are those of the formula (I) wherein a + b + c = 3-10, especially 3-7. Particularly preferred silicone compounds are as follows.

The compounds (A), (B) and (C) can be used alone or in any combination thereof.

Cyclic silicone compounds suitable for the gas phase treatment include, for example, dihydrogenhexamethylcyclotetrasiloxane, trihydrogenpentamethylcyclotetrasiloxane, tetrahydrogentetramethylcyclotetrasiloxane, dihydrogenoctamethylcyclopantasiloxane, trihydrogen Hydrogen heptamethylcyclopentasiloxane, tetrahydrogenhexamethylcyclopentasiloxane and pentahydrogenpentamethylcyclopentasiloxane can be mentioned. These compounds can be used alone or in any combination.

Specific examples of linear silicone compounds suitable for gas phase treatment include 1,1,1,2,3,4,4,4-octamethyltetrasiloxane, 1,1,1,2,3,4, Mention may be made of 5,5,5-nonamethylpentasiloxane and 1,1,1,2,3,4,5,6,6,6-decamethylhexasiloxane.

Generally, silicone compounds having at least two Si-H moieties in the molecule are preferred. However, the amount of hydrogen atoms becomes so large that it becomes difficult to obtain a silicone compound containing a silicon atom bonded to two hydrogen atoms.

There are two types of structures of the silicone polymer film covering the powder surface. That is, when the polymerization occurs by a siloxane bond (-Si-O-Si-), the resulting silicone polymer has a linear structure containing -Si-O-Si- units, and preferably has a weight average molecular weight of 200,000 or more. .

On the other hand, the polymerization in the case caused by the dehydrogenation reaction of hydrosilyl bond (Si-H) in the presence of H ₂ O or O ₂ in small or trace amounts, following the polymerization of Si-H moieties: Derived from The silicone polymer will comprise a network with units.

Preferred reticulated polymers are those in which 5-90%, preferably 20-80%, of all silicon atoms are as described above in the polymer coating. It is converted to a unit. The content of this unit can be determined from the infrared absorption spectrum of the methyl group in the polymer film.

The amount of the silicone polymer to be coated on the treated powder in the first stage varies depending on the type of powder and the surface area of the powder, but is 0.005 to 9% based on the total weight of the coated powder.
Preferably it is 5% by weight.

Prior to performing the first coating step of the modification process according to the present invention, the powder may be subjected to any conventional treatment (eg, alkali cleaning, acid cleaning, plasma treatment). When the powder has many acid sites (for example, kaolinite, iron oxide, manganese violet), it is preferable to carry out alkali cleaning. This is because, according to the present invention, when the silicone compound is subsequently brought into contact with the surface and polymerized, a silicone polymer film having a crosslinked structure is easily formed.

Furthermore, if the pigment and the ultraviolet absorbent are adsorbed to the powder before the first-stage treatment step, a powder having the color and the ultraviolet absorbing function can be obtained. In addition, when the ultraviolet absorbent is intercalated between the layers of the clay mineral, it may be unstable and desorbed by a solvent or the like simply by being put between the layers, but according to the present invention, further coated with a silicone polymer. If it does, it will not desorb.

When the ultraviolet absorbent is adsorbed on the powder, a new active site may be generated. In this case, a polymer is formed on the surface of the ultraviolet absorbent adsorbed by contacting the silicone compound monomer. As the ultraviolet absorber to be used, 2-hydroxy-4-methoxybenzophenone,
2,2'-dihydroxy4,4'-dimethoxybenzophenone, 2,2'-dihydroxy4,4'-dimethoxybenzophenone sulfate, 2,2 ', 4,4'-tetrahydroxybenzophenone, 2,2'-dihydroxy4 , 4'-Dimethoxybenzophenone, 2-hydroxy-4-methoxybenzophenone sulfate, 2- (2-hydroxy-5'-methylphenyl)
Benzotriazole, paradimethylaminobenzoic acid 2-
Ethylhexyl, amyl paradimethylaminobenzoate,
Examples thereof include methyl 2,5-diisopropylcinnamate and urocanic acid.

The silicone polymer formed on the powder in the first coating step of the modification of the present invention is, for example, a compound represented by the general formula (Wherein R ²¹ , R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are each independently a hydrocarbon group, especially a lower alkyl group or an aryl group, and R ²² is a hydrogen atom or a hydrocarbon group, especially an alkyl group or an aryl group. X is an integer of 1 or more, y and z are 0 or an integer of 1 or more, and x and y are In particular, a molecular weight of 200,000 or more (weight average). The silicone polymer having a molecular weight of 200,000 or more does not elute even when treated with a solvent such as chloroform, and can form a complete coating on the powder. Therefore, even the processed powder at this stage has excellent properties as compared with the above-mentioned prior art.

In the above formula (II), as the value of 100x / (x + y) increases, the network structure of the silicone polymer increases, and the possibility of release even when entering the solvent system decreases. The ratio between x and y can be calculated from the infrared absorption spectrum.

Representative examples of the silicone polymer of the formula (II) include a compound represented by the formula Wherein R ²¹ and R ²³ are a lower alkyl group such as a methyl group or an ethyl group or an aryl group such as a phenyl group, and x and y have the meanings given in the above formula (II). Or expression Wherein R ²¹ and R ²³ are a lower alkyl group or an aryl group, R ²² is a hydrogen atom, an alkyl group or an aryl group, and x and y have the meanings given in the above formula (II). Can be mentioned.

More specific examples of the silicone polymer of the formula (II) include [CH ₃ SiO _3/2 ] _x [(CH ₃ ) HSiO] _y , [CH ₃ SiO _3/2 ] _x [(CH ₃ ) HSiO] _y [CH ₃ SiO _1/2 ] _z , [CH ₃ SiO _3/2 ] _x [(C ₂ H ₅ ) HSiO] _y , [CH ₃ SiO _3/2 ] _x [(C ₅ H ₁₁ ) HSiO] _y , (CH ₃ SiO _3/2 ) _x [(C ₈ H ₁₇ ) HSiO] _y , (CH ₃ SiO _3/2 ) _x [(C ₆ H ₁₃ ) HSiO] _y , (CH ₃ SiO _3/2 ) _x ((CH ₃ ) HSiO) _y , (CH ₃ SiO _1/2 ) _z , (CH ₃ SiO _3/2 ) _x [(C ₂ H ₅ ) HSiO] _y , (CH ₃ SiO _1/2 ) _z , ( CH ₃ SiO _{3/2] x} [(C ₅ H ₁₁₎ HSiO] _y, [CH ₃ SiO _{1/2] z,} [CH ₃ SiO _{3/2] x} [(C ₈ H ₁₇₎ HSiO] _y, [ CH ₃ SiO _{1/2] z,} may be mentioned [CH ₃ SiO _{3/2] x} [(C ₆ H ₁₃₎ HSiO] _y, the [CH ₃ SiO _{1/2] z,} and the like.

The coating amount of the silicone polymer of the treated powder in the first stage varies depending on the type of the powder and the surface area of the powder, but is about 0.1 to 50% by weight, preferably 0.1 to 20% by weight.
More preferably, it is 0.2 to 5.0% by weight. If the content is less than 0.1% by weight, it is not optimal for imparting effective stability to the powder. If the content is more than 50% by weight, the bonding between the powders proceeds to cause agglomeration and dispersibility. Not optimal.

There are two types of structures of the silicone polymer film coated on the powder surface. That is, when the polymerization occurs by a siloxane bond (-Si-O-Si-), the resulting silicone polymer has a linear structure containing -Si-O-Si- units, and preferably has a weight average molecular weight of 200,000 or more. .

On the other hand, the polymerization in the case caused by the dehydrogenation reaction of hydrosilyl bond (Si-H) in the presence of H ₂ O or O ₂ in small or trace amounts, following the polymerization of Si-H moieties: Derived from The silicone polymer will comprise a network with units.

Preferred reticulated polymers are those in which at least 20% of the total silicon atoms are It is converted to a unit. The content of this unit can be determined from the infrared absorption spectrum of the methyl group in the polymer film.

The silicone compounds of formula (I) that are contacted with the powder to form a silicone polymer coating consist of two groups. The first group corresponds to the case where c = 0 in the above formula (I), and has a general formula (R ¹ HSiO) _a (R ² R ³ SiO) _b (III) wherein R ¹ , R ² , R ³ , a and b have the same meaning as described above, but preferably R ¹ , R ² and R ³ are each independently carbon atoms which may be substituted with at least one halogen atom (particularly fluorine atom). A lower alkyl group or an aryl group (e.g., a phenyl group), wherein the sum of a and b is 3 to 100, particularly 3 to 7]. Preferred cyclic silicone compounds are for example of the formula Wherein R ¹ is a lower alkyl group such as a methyl group or an ethyl group or an aryl group such as a phenyl group, and a is 3 to 7. (A compound in which R ¹ is a methyl group is easily available.) ) Or expression Wherein R ¹ and R ² are a lower alkyl group or an aryl group, R ³ is an alkyl group or an aryl group, and a and b have the same meanings as in the above formula (III), a +
b is 3 to 100] or a compound represented by the formula: Wherein R ² and R ³ are a hydrogen atom, an alkyl group or an aryl group, and b is a positive integer, or a compound represented by the formula (Wherein, R ² and R ³ are independently a hydrogen atom, a carbon atom 1
Or a fluorinated hydrocarbon group having 1 to 6 carbon atoms, and b is a positive integer.

Representative examples of the cyclic silicone compound of the formula (III) are as follows.

Further, specific examples of the cyclic silicone compound of the formula (III) include dihydrohexamethylcyclotetrasiloxane, trihydropentamethylcyclotetrasiloxane, tetrahydrotetramethylcyclotetrasiloxane, dihydrooctamethylcyclopentasiloxane,
Examples include trihydroheptamethylcyclopentasiloxane, tetrahydrohexamethylcyclopentasiloxane, and pentahydropentamethylcyclopentasiloxane.

It is desirable that two or more hydrogen atoms be present in one molecule. In addition, those having too many hydrogen atoms are difficult to obtain because there are those in which two hydrogen atoms are bonded to silicon atoms.

The second group of the silicone compounds of the formula (I) corresponds to the case where c = 2 in the formula (I), [Wherein, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , a and b have the meanings given in the above formula (I), and c is 2, preferably R ¹ to R ⁶ is independently a lower alkyl group or an aryl group having 1 to 4 carbon atoms (eg, a phenyl group) which may be substituted with at least one halogen atom (particularly, a fluorine atom); Is 1 to 100, especially 2
5] is a linear silicone compound represented by the formula:

The linear silicone compound has, for example, the formula (Wherein, R ¹ and R ^{3 to} R ⁶ are a lower alkyl group or an aryl group, R ² is an alkyl group or an aryl group,
a is a positive integer, b is 0 or a positive integer, and c is 2), or a compound represented by the formula: (Wherein, R ^{2 to} R ⁶ are a hydrogen atom, an alkyl group or an aryl group, b is a positive integer, and c is 2), or a compound represented by the formula: (Wherein, R ^{2 to} R ⁶ independently represent a hydrogen atom, a carbon number of 1 to 6
Wherein b is a positive integer and c is 2).

Representative examples of the linear silicone compound of formula (IV) include compounds of the formula (Wherein a is preferably from 1 to 500, particularly preferably from 2 to
5) methyl hydrogen polysiloxane oil represented by the following formula:

In addition, when it is desired to proceed the reaction slowly by reducing the number of Si—H groups, the formula (Where a + b is from 1 to 500). In each of the above formulas (IV d) and (IV e), it is preferable that two or more hydrogen atoms exist in one molecule. In addition, 1 in formulas (IV d) and (IV e)
It is also possible to use one or more methyl groups replaced by one or more methyl groups, propyl groups or phenyl groups.

In the above formula (IV), those having too many hydrogen atoms are difficult to obtain because there are those in which two hydrogen atoms are bonded to a silicon atom.

Specific examples of the linear silicone compound of the formula (III) include 1,1,1,2,3,4,4,4-octamethyltetrasiloxane, 1,1,1,2,3,4,5 , 5,5-Nonamethylpentasiloxane, and 1,1,1,2,3,4,5,6,6,6-decamethylhexasiloxane.

The feature of the gas phase treatment is that the silicone compound
This is an energy-saving treatment method that utilizes the fact that the powder is left in a low partial pressure state where it evaporates at a temperature of 100 ° C or less, adsorbed on the powder in a molecular state, and polymerized from the active points on the surface. This is completely different from the conventional method of spraying a treating agent and polymerizing it by heat. The above-described gas phase processing has the following characteristics.

(1) Polymerization is performed on the powder surface without baking treatment, which is effective for energy saving and does not change color.

(2) Since no crushing force is used, it is effective in energy saving, and there is no change in particles and no aggregation. Also, there is no color change due to the crushing force.

(3) The processing is simple, there is no waste of the processing agent, and the processing can be performed uniformly because of the gas phase processing.

(4) Water-repellency and surface activity of the treated powder are almost completely blocked.

(5) Ultrafine powder (e.g., having a particle size of 0.005-0.05 [mu] m) can be effectively coated with a uniform and thin silicone polymer without causing undesirable aggregation.

As described above, in the first step of the present invention, one or more silicone compounds and powder are put in, for example, separate open containers, and these containers are left in a common closed system. Adsorbs on the powder surface in a molecular state.

In this state, the silicone compound is vaporized by the partial pressure at that temperature, and the adsorption equilibrium is maintained on the powder. If the powder has no polymerization activity, the silicone compound is desorbed when the powder is taken out, and the powder returns to the original surface. If the powder has polymerization activity, the powder is polymerized on the powder. When the polymerization is performed, the partial pressure of the silicone compound on the surface of the powder is reduced, so that the silicone compound in the container is further vaporized and supplied.

In order to cause polymerization on the surface, heat is generally used or a polymerization catalyst is used. However, according to the knowledge obtained by the present inventors, the powders, i.e., inorganic pigments, metal oxides, metal Hydroxides, organic pigments, pearlescent materials, silicate minerals, porous materials, carbon, metals, biopolymers, mica and composite powders have a surface-catalyzing action of ring-opening polymerization and Si-H groups. It has been found that the catalyst has a catalytic action to cross-link each other and form a bond of Si-O-Si.

The silicone compound adsorbed on the surface of the powder forms a network-like silicone polymer film which is successively crosslinked by this surface activity. When the powder surface is coated with the silicone polymer film in this manner, the surface active sites of the powder are blocked, and the subsequent adsorption and crosslinking reactions do not proceed, and the film formation is stopped. After degassing, the unreacted silicone compound is removed, and a powder coated only with the silicone polymer can be produced.

The standing temperature of the powder and the silicone compound at 100 ° C. or less is sufficient, and the conventionally required temperature of 150 ° C. is not required, because the powder has surface activity.

The powder to be treated can be dried in advance,
Moisture may be contained to some extent. Although high-temperature heating is not required to obtain a powder coated with a silicone polymer film in this way, the type of powder (heat resistance)
May be heated to, for example, about 300 ° C., 200 ° C., or 140 ° C., in which case 100 × /
The value of (x + y) does not exceed the scope of the present invention merely by increasing the value.

As described above, according to the present invention, first, the silicone compound is brought into contact with the powder surface, and the silicone compound is polymerized by the presence of active sites distributed over the entire surface of the powder. Therefore, a uniform and thin polymer film is formed. After a thin layer of silicone polymer has been formed, substantially no polymerization occurs thereon. Therefore, the thickness of the silicone polymer film is generally 3 ° to 30 °. On the other hand, when thermal polymerization is caused, polymerization for forming a thin layer is impossible. Further, when the polymerization is carried out in the presence of a catalyst, the polymerization mainly occurs around the catalyst, so that it is impossible to uniformly coat only the surface of the powder.

The formation of a uniform and thin film of the silicone polymer can also be carried out by the solid phase treatment described above, but it is easier to use the liquid phase treatment, and it is particularly preferred to carry out the gas phase treatment.

In the first step of the modification according to the present invention, the unreacted Si-H portion remains in the silicone polymer formed on the powder surface by the above-mentioned treatment.

That is, when the above-mentioned silicone compound is brought into contact with the powder surface to carry out polymerization, cross-linking of Si-H groups occurs on the powder surface, a network structure is formed, and the surface is coated with a silicone polymer film. However, cross-linking occurs due to steric hindrance
100% does not progress. Therefore, the remaining Si-H portion is present and tends to be slightly unstable under severe conditions such as alkali and acid. In the present invention, a spacer compound is bonded to the remaining Si-H portion in the second step described later, so that generally stable powder can be obtained.

In the first step of the present invention, the reactive portion Si-H in the silicone polymer film formed by the above treatment is used.
The moiety can be changed to another reactive moiety, ie, a derivative moiety of Si-H, if desired.

For example, a Si-H moiety is hydrolyzed to a Si-OH moiety by a known method (eg, acid or base). Also,
The Si-OH moiety is halogenated, for example, with a thionyl halide to convert it to a Si-halogen moiety (eg, Si-Cl).

The conversion of the reactive moiety may be appropriately selected depending on the type of the spacer compound used in the second step, the type of the chemical modification performed in the third step, and the like.

In the second stage of the modification of the present invention, a spacer compound is used. The spacer compound is a compound containing at least one Si-bonding moiety and at least one chemically modified accepting moiety in the spacer compound body.

The “Si-bonding portion” means a portion capable of reacting with the reactive portion prepared in the silicone polymer film by the first step and bonding to the Si atom. Thus, when the reactive moiety is a Si-H moiety, the Si-bonding moiety is, for example, a moiety having a carbon-carbon double or triple bond, or an OH or SH terminal group. When the reactive moiety is a Si-OH moiety, the Si-bonding moiety is typically a moiety having a bonding site of a silane coupler such as a halogen atom, an alkoxy group (for example, a methoxy group or an ethoxy group), an OH group, and the like. is there. When the reactive moiety is a Si-halogen moiety,
For example, a moiety having a free amino group, a mono- or di-substituted amino group or a magnesium halide group.

"Chemical modification accepting moiety" means a moiety capable of undergoing all types of chemical modifications generally known in the chemical arts.

“Chemical modification” includes all chemical treatments. For example, rearrangement reaction, isomerization reaction, decomposition reaction, elimination reaction, solvolysis reaction, esterification reaction, isotope conversion reaction, substitution reaction, addition reaction, condensation reaction, oxidation reaction, reduction reaction, and further nitration, Includes sulfonation, halogenation, amination, diazotization, alkylation, acylation, and the like (these lists of reactions are exemplary and do not limit the chemical modifications of the present invention).

Therefore, the above-mentioned chemically modified acceptor moiety is a moiety that exhibits chemical activity by any means. For example, aliphatic carbon-carbon unsaturated group, aromatic ring, alicyclic unsaturated group, saturated or unsaturated heterocyclic ring, halogen atom, carboxylic acid group, peroxy group, thiocarboxylic acid group, sulfonic acid group , A sulfinic acid group or a sulfenic acid group or an ester group or a salt group thereof, an acid anhydride group, an acid halide group,
Amido group, hydrazide group, imide group, cyano group, isocyano group, cyanato group, isocyanato group, thiocyanato group, isothiocyanato group, formyl group, oxo group, thioformyl group, thioxo group, hydroxy group, mercapto group, amino group, imino group , An ether group, a sulfide group, and the like (these groups are merely examples, and do not limit the above-mentioned chemical modification accepting moiety).

The `` spacer compound body '' includes the Si-bonding moiety and the chemical modification accepting moiety at its terminal or inside,
A chemically inert part, generally consisting of a saturated hydrocarbon group. The spacer compound may consist only of the Si-bonding moiety and the chemically modified accepting moiety, and the spacer compound body may not be present. The spacer compound is composed of a plurality of Si
It can include a binding moiety and / or a chemically modified acceptor moiety.

The reaction between the Si-bonding part of the spacer compound and the reactive part of the silicone polymer film is carried out under conditions that do not affect the above-mentioned chemical modification accepting part (if there is no hindrance to the chemical modification operation in the subsequent third step, There is no problem if the chemical modification accepting moiety is changed by the above reaction). In some cases, it is preferable to protect the chemically modified accepting moiety.
A known method may be used for the various functional groups and the protection means.

An object of the second step of the present invention is to provide a spacer having a chemically modified acceptor by reacting a reactive moiety in a silicone polymer film with an Si-bonding portion of a spacer compound to bond the spacer compound to the silicone polymer film. The purpose is to introduce groups (residues of the spacer compound) onto the silicone polymer film.

When the reactive moiety is a Si-H moiety, a compound having an OH group or SH group as the Si-bonding moiety, for example, an amino acid (for example, cysteine) can be used. Further, an unsaturated compound having at least one carbon-carbon double bond or triple bond as the Si-bonding moiety can be used.

Suitable unsaturated compounds have the general formula (VI) In the formula, R ¹¹ , R ¹² , R ¹³ and R ¹⁴ each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a mercapto group, an acyloxy group, an alkoxy group, an amino group, a nitro group, a carboxyl group, a sulfo group, Alternatively, a substituted or unsubstituted hydrocarbon group having 1 to 30 carbon atoms [eg, an aliphatic group (eg, an alkyl group, an alkenyl group, an alkynyl group), an aromatic group (eg, a phenyl group, a naphthyl group), a heterocyclic group] (For example, nitrogen atom, oxygen atom or sulfur atom 1 as a hetero atom
Alicyclic group (for example, cycloalkyl group, cycloalkenyl group, cycloalkynyl group), spiro compound residue or terpene compound residue],
Alternatively, R ¹¹ and R ¹³ represent a carbon-carbon bond, and -C =
Together with C- can form -C≡C-,
Alternatively, R ¹² and R ¹⁴ together with —C ＝ C— can form an alicyclic group, provided that all of R ^{11 to} R ¹⁴ are simultaneously a hydrogen atom, a saturated aliphatic group and The compound of (1), which does not consist solely of a saturated alicyclic group.

In formula (VI), the hydrocarbon groups R ^{11 to} R ¹⁴ are represented by the formula (V
In addition to the double or triple bond in the compounds of I),
The chemical modification accepting moiety can be substituted with one or more unsaturated hydrocarbon groups (eg, as exemplified in formula (VI) above) and / or one or more functional groups.
Representative examples of the functional group include a halogen atom, an amino group, a carboxyl group, a sulfo group, a mercapto group, an epoxy group,
Examples include a cyano group, a nitro group, a hydroxyl group, an alkoxy group, an alkoxycarbonyl group, an acyl group, a vinyl group, an acyloxy group, a dialkylamino group, a quaternary ammonium group, an amide group, and a polyalkylene ether group.

Preferred spacer compounds are unsaturated compounds having a double bond at one end and a reactive functional group at the other end, such as allyl glycidyl ether, styrene, allyl benzene, allyl phenyl ether, allyl phenol, allyl bromide, Allyl chloride, allyl iodide, allyl alcohol, allylamine, 4-allylveratol, 2-
(Allyloxy) ethanol, allyl isocyanate,
N-allyldimethylamine, N-allyldiethylamine, 1-allyl-3,4-dimethoxybenzene, allyl isothiocyanate, allylacetic acid, p-vinylaniline, allylsulfonic acid, vinyltrimethoxysilane, vinyltriethoxysilane, vinylacetic acid 2-vinylnaphthalene, 2-vinylpyridine, 4-vinylpyridine, N-vinyl-2-pyrrolidone, polyoxyethylene allyl ether (OE unit 1 to 9), acetylene, 3-chloropropyldimethylvinylsilane, 1-octyne 1 , 7-octadiyne and the like.

In the addition reaction to the Si-H portion, the powder after the first-stage treatment and the Si-H-reactive spacer compound are mixed at a temperature of 300 ° C or lower, preferably 0 to 250 ° C in the presence of a catalyst at a gas phase liquid phase or a solid phase. For one hour or more.

As the catalyst, a platinum group catalyst, that is, a compound of ruthenium, rhodium, palladium, osmium, iridium, and platinum is suitable, and a compound of palladium and platinum is particularly preferable. For palladium, palladium chloride (I
I), Ammonium tetraammonium palladium (II) ammonium, palladium (II) oxide, palladium (II) hydroxide
And the like. For platinum-based platinum (II) chloride, tetrachloroplatinic acid (II), platinum chloride (IV), hexachloroplatinic acid (IV), ammonium hexachloroplatinate (IV), platinum oxide (II), platinum hydroxide (II) , Platinum dioxide (IV),
Platinum oxide (IV), platinum disulfide (IV), platinum sulfide (IV),
And potassium hexachloroplatinate (IV). After adding tri-n-alkyl (C1-8) methylammonium chloride or tri-n-alkylamine to these palladium-based compounds and platinum-based compounds and performing ion pair extraction with a water / organic solvent system, Can be used. Furthermore, amine catalysts such as tributylamine or polymerization initiators can be used. The addition reaction can be carried out using ultraviolet light, γ-ray, plasma, or the like.

The coating amount of the silicone polymer having a spacer group is
Although it can be varied widely depending on the purpose of the reforming,
The amount of the spacer group-containing silicone polymer is preferably 0.005 to 95% by weight based on the total weight of the modified powder after the treatment.

As an alternative to introducing a spacer compound into the Si-H group,
For the Si-OH moiety generated by hydrolyzing the Si-H moiety,
There is a method of performing a condensation reaction or a substitution reaction of a Si-OH-reactive spacer compound.

The hydrolysis of the Si-H group is 200 ° C or less, preferably 0 to 100 ° C.
By contacting with a gas phase or a liquid phase for 5 minutes or more.

When the hydrolysis is carried out by gas phase treatment, the siliconized powder and a volatile acid or base (for example, hydrochloric acid or aqueous ammonia) are put in separate containers in a closed room, and the upper part is opened. Just good. At this time, when a concentrated acid or base is used, the Si-H portion is partially substituted with the acid or base (for example, Si-Cl, Si-NH ₂ ), and the base is adsorbed on the generated Si-OH. Therefore, if necessary, the treated powder is stirred while being heated in an aqueous alcohol solution to complete the hydrolysis, or washed with an aqueous alcohol solution containing a low-concentration acid or base.

When the hydrolysis is carried out by a liquid phase treatment, the silicone-treated powder may be carried out in an aqueous alcoholic system containing an acid or a base according to a conventional method.

It is preferable that the silicone-treated powder hydrolyzed in the liquid phase treatment step is not dried after filtration. This is the Si-
This is because OHs are crosslinked on the powder by drying to form Si—O—Si bonds, and the bonding portion may be reduced. When the next step of introducing a spacer group is carried out in a non-aqueous system, it is preferable to replace the solvent of the hydrolyzed silicone-treated powder with the solvent used in the reaction and store it in a wet state.

The Si-OH reactive spacer compound is a silane coupler. In addition, if Si-OH is changed to Si-Cl, a dialkylamine or Grignard reagent can also be used as the spacer compound.

As the silane coupler, a silane coupler having at least one functional group (e.g., a halogen group, an alkoxy group, or a hydroxyl group) capable of binding to a Si-OH group and further having at least one chemically modified accepting moiety can be used.

Suitable silane couplers have the general formula (VII) [Wherein at least one of R ²¹ , R ²² , R ²³ and R ²⁴ is
A halogen atom, an alkoxy group (for example, a methoxy group, an ethoxy group) or a hydroxyl group, and others independently of each other a hydrogen atom, a halogen atom, a hydroxyl group, an alkoxy group (for example, a methoxy group, an ethoxy group), a glycidoxyalkyl group ( For example, γ-glycidoxypropyl group), cyanoalkyl group (for example, 3-cyanopropyl group), aminoalkyl group (for example, 3-cyanopropyl group), phenylalkyl group (for example, phenethyl group), and chloroalkyl group (for example, γ- Chloropropyl group), a dialkylaminoalkyl group (for example, an N, N-diethyl-3-aminopropyl group), an alkyl group, an alkenyl group, an alkynyl group, and a phenyl group].

Preferred spacer compounds among the silane couplers are those having a reactive functional group (chemically modified accepting moiety) at the terminal, for example, γ-glycidoxypropyltrimethoxysilane, 3-cyanopropyldimethylchlorosilane, aminopropyltrimethoxysilane, γ-chloropropyltrimethoxysilane, (N, N-diethyl-3-aminopropyl) trimethoxysilane, and phenethyltrimethoxysilane.

The silane coupler can be treated in a liquid phase by a conventional method. For example, in the case of a silane coupler having a halogen group as a binding group, the silane coupler is added to the silicone-treated powder that has been solvent-replaced with toluene after hydrolysis for 0.5 to 48 hours, preferably 2 to 10 hours by heating and refluxing. Spacer groups can be attached to the siliconized powder. Further, in the case of a silane coupler having an alkoxy group as a binding group, a silane coupler is added to the silicone-treated powder that has been solvent-replaced with hydrous alcohol or hydrous acetone after hydrolysis, and 0 ° C to 100 ° C, preferably room temperature to 60 ° C. By stirring at a temperature for 0.5 to 24 hours, preferably 1 to 5 hours, a spacer group can be introduced into the siliconized powder.

The Si—H portion of the silicone polymer covering the powder is hydrolyzed to Si—OH, and then halogenated with, for example, thionyl chloride to obtain Si—Cl. When an amine is reacted with the amine in a conventional manner, the amino group, the first, the second, and the third
Amino is formed. An arbitrary spacer group can be introduced by reacting a Grignard reagent R-MgX with the Si-Cl moiety in a conventional manner.

In the third step of the present invention, the chemically modified accepting moiety contained in the spacer group introduced up to the second step is chemically modified to convert it into a desired functional moiety.

Here, “chemical modification” includes any known chemical treatment as defined above. The term "functional moiety" means any moiety having any useful action, and includes, for example, a functional group or a residue of a physiologically active substance.

Examples of the functional group include acid residues such as carboxylic acid, sulfonic acid and phosphoric acid residues, base residues such as amino groups and quaternary ammonium salt groups, and hydrophilic groups such as hydroxyl groups and polyoxyethylene groups. Polyoxypropylene group, carboxyl group, sulfo group, amino group, quaternary ammonium group, hydrophobic group such as alkyl group, alkenyl group, alkynyl group, phenyl group, naphthyl group, etc.
Epoxy group, alkoxy group, cyano group, nitro group and the like.

A representative example of a bioactive substance is an enzyme. Enzymes, for example,
Lipase, urease, urokinase, glucose oxidase, lysozyme and the like.

The chemical modification in the third stage does not mean only a single chemical treatment. That is, it includes performing one or more types of chemical treatments one after another over a plurality of steps.

As described above, the chemical modification in the third step of the present invention includes one or a combination of a plurality of known chemical treatments of all kinds, and the specific contents of these treatments are described in general literature on chemistry. Those skilled in the art can appropriately and easily carry out the procedure with reference to those described in.

Hereinafter, the chemical modification in the third step of the present invention will be specifically described for the specific chemical modification accepting moiety contained in the spacer group, but it goes without saying that this description does not limit the present invention.

Epoxy group Silicone polymer-coated powder to which a spacer compound (for example, allyl glycidyl ether) having an epoxy group as a chemical modification accepting moiety has been added, is hydrolyzed with a dilute acid (for example, dilute sulfuric acid) to introduce a diol group. Can be. When a diol group is oxidized with an oxidizing agent (for example, potassium permanganate), a carboxyl group can be introduced.

Further, an enzyme (eg, lipase or glucose oxidase) can be immobilized on the carboxyl group using a condensing reagent (eg, dicyclohexylcarbodiimide reagent or K. Woodward reagent).

The epoxy group is a dialkylamine (for example, N-
Dialkylamination with dimethylamine, N-diethylamine) can introduce a dialkylamino group. Further, when an alkyl halide is reacted with a dialkylamino group (eg, methyl iodide, ethyl iodide), a quaternary ammonium salt can be introduced.

When an epoxy group is sulfonated with a sulfonating agent (for example, sodium sulfite), a sulfone group can be introduced. The sulphone group can be left in salt form after washing with dilute acid with counterions such as Na ⁺ , Ca ²⁺ and Zn ²⁺ .

An amino group can be introduced into the epoxy group by adding ammonia. Further, a condensing reagent [for example, N
-Hydroxy-5-5-norbornene-2,3-dicarboximide or 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride] to immobilize an enzyme (eg, lipase or urease). it can.

The epoxy group is a cyanide compound (for example, hydrogen cyanide,
Cyanation with potassium cyanide) can introduce a cyano group.

Glycerin, diglycerin and polyglycerin can be introduced into the epoxy group when boron fluorides (for example, zinc boron tetrafluoride) are used as a catalyst.

Phenyl group When a spacer compound (for example, styrene or allyl phenyl ether) having a phenyl group as a chemically modified acceptor is added to a silicone polymer-coated powder, the sulfone group is introduced when sulfonated with a sulfonating agent (for example, fuming sulfuric acid). it can. Sulfone groups include Na ⁺ , Ca ²⁺ and Zn
It can be kept in a salt form with a counter ion such as ²⁺ .

The phenyl group is nitrated with a nitrating agent (for example, nitric acid), and then reduced with a reducing agent (for example, hydrochloric acid).
Amino groups can be introduced.

Further, as described above, the enzyme can be further immobilized on the amino group using a condensing reagent. When an alkyl orthophosphate (eg, methyl orthophosphate or ethyl orthophosphate) is reacted with an amino group, a dialkylamino group can be introduced.

Further, when an alkyl halide is further reacted with a dialkylamino group, a quaternary ammonium base can be introduced.

The carboxyl group can be introduced into the phenyl group by blowing carbon dioxide in a low-polarity solvent (for example, pentane) in the presence of potassium tert-butoxide as a catalyst. Further, as described above, the enzyme can be immobilized on the carboxyl group using a condensing reagent. Further, the carboxyl group becomes an aldehyde group when reduced with a reducing agent (for example, diisobutyl aluminum hydride) in a polar solvent (for example, dioxane), and further, when an ammonia gas is blown in a toluene solvent in the presence of iodine, a cyano group is formed. Can be introduced.

Hydroxyl group When a spacer compound (for example, hydroxypropyl group) having a hydroxyl group as a chemically modified accepting moiety is added to a silicone polymer-coated powder, a carboxyl group can be introduced by oxidation with an oxidizing agent (for example, potassium permanganate). Further, the carboxyl group can immobilize the enzyme by the method described above, and the cyano group can be introduced via the aldehyde.

When a hydroxyl group is oxidized with chromic acid, an aldehyde group can be introduced. Further, the aldehyde group can directly bind proteins and enzymes by a Schiff base forming reaction with the amino group.

Halogen A silicone polymer-coated powder to which a spacer compound (for example, allyl chloride) having a halogen as a chemical modification accepting moiety is added, is subjected to a substitution reaction with ammonia,
Amino groups can be introduced.

Further, the halogen is sulfonated by a sulfonating agent (for example, sodium sulfite), and a sulfo group can be introduced.

Furthermore, when a halogen is cyanated with a cyanide, a cyano group can be introduced.

Vinyl group When a spacer compound having a carbon-carbon triple bond (for example, acetylene) is added to the silicone polymer-coated powder, a vinyl group as a chemical modification accepting moiety can be introduced.
In addition, hydrogen halide (for example, hydrogen iodide)
Is added to allow halogenation to be introduced. Subsequently, if the halogen is replaced by a sulfonating agent or a cyanide,
A sulfo group or a cyano group can be introduced.

As described above, it is preferable that the spacer compound has a Si-bonding moiety and a chemically modified accepting moiety at both ends of the compound.However, for example, as in acetylene, the Si-bonding moiety and the chemically modified accepting moiety are carbon- Some also include a carbon triple bond together.

In the present invention, as described above, by introducing an appropriate chemical modification accepting moiety in the second step, any desired function can be imparted to the powder in the subsequent third step. That is, as long as the chemical modification treatment means is known, it is possible to impart a desired function to the powder substantially indefinitely and freely.

For example, a sulfonic acid group,
A powder into which a carboxylic acid group, an amino group, a diethylamino group, a phenyl group, or a cyano group has been introduced can be used as an ion exchanger or a filler for liquid chromatography because of its excellent acid resistance and base resistance.

Furthermore, if, for example, an epoxy group or an amino group is finally introduced, a powder having a high affinity for a thermosetting resin, a thermoplastic resin and an elastomer rubber can be obtained, and resin sealing, a coated sand, a sealant, a filler, Useful for pigments, paints, inks, adhesives, primers and plastics.

In particular, when the silicone polymer-coated titanium mica into which the epoxy group is finally introduced is incorporated into the paint, the weather resistance of the coating film is improved as compared with the untreated titanium mica.

Next, typical uses of the modified powder according to the present invention will be described.

The modified powder according to the present invention can be advantageously used as an ion exchanger or a filler for liquid chromatography.

Conventionally, packing materials for liquid chromatography have been used in which functional groups have been directly introduced into silica gel with a silane coupler, but the peak of a polar substance cannot be obtained sharply due to the silanol groups remaining in the unreacted portion. However, it has a drawback that it cannot be used for a long period of time because of its poor acid resistance, especially base resistance. In particular, a packing for anion exchange chromatography using silica gel as a carrier is substantially impossible to regenerate using an alkali. On the other hand, packing materials for ion exchange chromatography using a porous polymer as a carrier are generally used, but since the flow rate cannot be increased due to poor pressure resistance, a sharp peak cannot be obtained and a long analysis time is required. It has the disadvantage that it takes time. Recently, it has been attempted to use carbon, titanium dioxide, and other materials having excellent acid resistance, base resistance, and pressure resistance as carriers for liquid chromatography. It was difficult to do.

The modified powder according to the present invention (particularly, porous powder such as silica gel, titanium dioxide, carbon, etc.) is thinly and uniformly coated with a silicone resin, and thus is completely free from the effects of silanol (in the case of silica gel). Excellent in resistance, base resistance, pressure resistance, and the pores are left as they are, and the functional groups are modified on the modified powder at extremely high density via spacer compounds. Therefore, it has excellent performance as a packing material for liquid chromatography.

The modified powders according to the invention can be advantageously incorporated, for example as pigments, in any coatings, such as solvent-type, powder-type, emulsion-type and aqueous-type coatings.

Paints are generally complex multi-component blends of resins, pigments, solvents, plasticizers, and other conventional paint additives. The purpose of incorporation of pigments in paints is (i) coloring, hiding power, physical properties (eg hardness, strength, adhesion), improved weather resistance, fluorescence, phosphorescence, magnetism, conductivity, and other pigment-specific properties (Ii) improving the fluidity of the coating liquid and improving the workability during coating; and (ii)
i) Prevent the generation and adhesion of rust, mold and pests.

In order to obtain such an effect, the interaction between the pigment and the resin or the dispersant has been studied. However, pigments have various properties depending on their type, for example, from hydrophilic to hydrophobic, which causes undesirable phenomena such as color separation in the same paint.

The modified pigments according to the invention have an undesired color coding because their surface is uniformly and substantially completely covered with a silicone polymer film.

Further, since the activity of the pigment surface is blocked by the silicone polymer film, it is possible to effectively prevent the coating film from deteriorating with time. Further, since the silicone polymer film on the surface of the modified pigment is transparent and thin, there is practically no color difference from the untreated pigment, and it is not necessary to correct the color difference due to the modification treatment of the present invention later. As the paint, it can be used for a nitrified cotton lacquer of a solution type paint, an oil-modified alkyd resin paint of a crosslinked type paint, a melamine resin baking paint, a polyamide resin cured epoxy resin paint, an unsaturated polyester resin paint and the like.

When the modified powder according to the present invention into which a hydrophobic group (for example, an alkyl group) is introduced at the final stage is blended into a cosmetic, the water repellency is high, the feeling of use is small, the makeup is not easily deformed, and the stability is low. High cosmetics can be obtained.

2. Description of the Related Art Conventionally, in cosmetics, especially in makeup cosmetics, a method of coating a powder in a formulation with silicone oil, metal soap silica powder, or the like has been used for the purpose of improving water repellency, a smooth use feeling, and excellent makeup durability. Was. In particular, coating with silicone oil is widely used, and a coating method using an organic solvent, a coating method using a mechanochemical reaction, a coating method in which silicone oil is mixed with another binding oil and sprayed onto powder, a bonding oil and silicone oil are used. A coating method and the like are known in which a mixed oil and a powder are mixed and then baked.

However, conventional techniques have not always satisfied water repellency, stability and usability. That is, the conventional silicone coating does not always have sufficient stability, and a metal soap coating, a silica coating or the like cannot provide sufficient water repellency.

On the other hand, when the modified powder of the present invention is blended, a cosmetic having sufficient water repellency, high stability, and excellent use feeling can be obtained.

Preferred powders to be added to cosmetics after treatment according to the present invention are powders usually used in cosmetics,
For example, talc, kaolin, sericite, muscovite, synthetic mica, phlogopite, biotite, biotite, lithia mica, vermiculite, magnesium carbonate, calcium carbonate, diatomaceous earth, magnesium silicate, calcium silicate, aluminum silicate, Inorganic powders such as barium silicate, barium sulfate, strontium silicate, metal tungstate, silica, hydroxyapatite, zeolite, boron nitride, ceramic powder, nylon powder, polyethylene powder, benzoguanamine powder, benzoguanamine powder, tetrafluoroethylene powder, distyrene Benzene pinhole polymer powder, organic powder such as microcrystalline cellulose, titanium oxide,
Inorganic white pigments such as zinc oxide, iron oxide (red iron), inorganic red pigments such as iron titanate, inorganic brown pigments such as γ-iron oxide, inorganic yellow pigments such as yellow iron oxide and loess, black iron oxide ,
Inorganic black pigments such as carbon black, inorganic purple pigments such as mango violet and cobalt violet, inorganic green pigments such as chromium oxide, chromium hydroxide, and cobalt titanate; inorganic blue pigments such as ultramarine and navy blue; titanium oxide coated Mica, titanium oxide coated bismuth oxychloride, bismuth oxychloride, titanium oxide coated talc, fish scale foil, pearl pigments such as colored titanium oxide coated mica, metal powder pigments such as aluminum powder, copper powder, red No. 201, red No. 202, Red No. 204, Red 2
05, Red 220, Red 226, Red 228, Red 405,
Orange No. 203, Orange No. 204, Yellow No. 205, Yellow No. 401 and Blue
Organic pigments such as No. 404, Red No. 3, Red No. 104, Red No. 106
No., Red No. 227, Red No. 230, Red No. 401, Red No. 505, Orange No. 205, Yellow No. 4, Yellow No. 5, Yellow No. 202, Yellow No. 203
No. 3, green No. 3 and blue No. 1 organic pigments such as zirconium, barium or aluminum lake, chlorophyll, β-
A natural coloring matter such as carotene is used, but is not limited thereto.

The molecular weight of the silicone polymer compound that coats the surface is
It is preferably at least 200,000. If the molecular weight is less than 200,000, it is difficult to obtain a complete coating and may not exhibit sufficient water repellency.

The amount of the modified powder according to the present invention is 1 to 1 in the total amount of the cosmetic.
100% by weight.

In addition to the modified powder of the present invention, this cosmetic may contain squalane, liquid paraffin, petrolatum, microcrystalline wax, ozokerite, ceresin, myristic acid, palmitic acid, stearic acid, oleic acid, isostearic acid, cetyl, if necessary. Alcohol, hexadecyl alcohol, oleyl alcohol, cetyl-2-ethylhexanoate, 2-ethylhexylpartatenate, 2-octyldodecyl myristate, 2-octyldodecyl gum ester, neopentylglycol-2-ethylhexanate, isooctylic acid Triglyceride, 2-octyldodecyl oleate, isopropyl myristate, triglyceride isostearate, coconut fatty acid triglyceride, olive oil, avocado oil, beeswax, myristyl myristate Mink oil, lanolin, dimethylpolysiloxane of various hydrocarbons, higher fatty acids, fats and oils,
Oils such as esters, higher alcohols, waxes, silicone oils, organic solvents such as acetone, toluene, butyl acetate, and ethyl acetate; resins such as alkyd resins and urea resins; plasticizers such as camphor and acetyltributyl citrate; and ultraviolet rays An absorbent, an antioxidant, a preservative, a surfactant, a humectant, a fragrance, water, alcohol, a thickener and the like can be added.

The cosmetic containing the modified powder of the present invention has high water repellency, spreads well on the skin, and has little makeup loss. Moreover, since the coating on the powder surface is strong, dense and homogeneous, a cosmetic with good stability can be obtained.

For example, a fragrance compounded in a cosmetic is often easily decomposed due to the activity of the powder, and often causes an unpleasant odor. However, this is not the case with a cosmetic compounded with the modified powder of the present invention.

In addition, since the modified powder of the present invention exhibits excellent dispersibility in powder, oil, or solvent, when a pearl pigment is used as the powder to be treated, it becomes a highly glossy cosmetic. In other words, when titanium oxide is used as the powder to be treated, it does not agglomerate and has excellent ultraviolet protection ability,
A cosmetic with a good makeup effect can be obtained.

Red No. 202 has two crystal forms, α-form and β-form, and β-form changes to α-form in the presence of water and changes color. Since the surface of such an organic pigment is also completely covered with the silicone coating according to the present invention, it does not change to the α-type even in the presence of water, and becomes a stable cosmetic.

Ultramarine blue is decomposed by acid and releases hydrogen sulfide, but the coating according to the present invention solves such a problem.

Further, one or more modified powders according to the present invention,
A cosmetic composition containing water and / or a lower alcohol and having excellent stability and usability can also be prepared.

Inorganic and organic powders have been conventionally blended in cosmetics as colorants, etc., but the surface may be hydrophilic or hydrophobic, or have surface activity, etc. When blending a powder into a cosmetic containing water and / or a lower alcohol, a measure such as applying a hydrophobic or hydrophilic surface treatment or adding a dispersant is often taken. .

Conventionally, a surfactant is adsorbed as a method known as a method of treating powder mixed with cosmetics.

 Adsorb fatty acids.

 The surface is coated with an alkylpolysiloxane.

Surface cross-linking polymerization is performed with methyl hydrogen polysiloxane.

Etc. are known.

However, the surface-adsorbed powder and the fatty acid-adsorbed powder have different adsorbing powers depending on the surface state of the adsorbed powder, so that it is difficult to perform a uniform surface treatment, and the surface activity of the solvent or coexisting surface Desorption may occur under the influence of substances.

On the other hand, the powder coated with the alkylene polysiloxane is uniformly coated, but has a drawback of being eluted by the solvent. The powder obtained by surface cross-linking polymerization of methyl hydrogen polysiloxane is excellent in uniformity and low solubility in a solvent because the polysiloxane is converted into a resin on the surface, but due to the remaining Si-H group. When it comes into contact with water, ethanol, or the like, there is a disadvantage that hydrogen gas is generated and the stability of the product is impaired. There is also danger during product manufacturing.

In addition, all of the above known methods require heat energy or mechanochemical energy, and the properties of the powder (particle shape, powder particle diameter, crystal type) during processing are required.
Also has the disadvantage of causing a change in

Therefore, in cosmetics containing water or a lower alcohol, such as emulsified cosmetics in which powders obtained by conventional treatments are blended, satisfactory ones are desired even though more stable products are desired. Did not.

On the other hand, by blending the modified powder according to the present invention into cosmetics containing water and / or alcohol such as emulsified cosmetics, the above-mentioned problems are solved, and stability and usability are solved. Excellent cosmetics can be obtained.

The stable powder according to the present invention not only has no decomposing effect on components usually blended in cosmetics, especially drugs and fragrances, but also powders treated by surface polymerization of methyl hydrogen polysiloxane. In addition, no hydrogen is generated even when contacted with water or a lower alcohol. Also, because the silicone polymer film is thin and highly transparent,
The powder which has been subjected to the surface treatment of the present invention has no difference in color tone from that of the untreated powder, and has no difference in magnetic properties even if it has magnetism.

In addition to such properties, the treated powder of the present invention has a high hydrophobicity, and is inherently well dispersed in the oil phase, and is stable by being added to the oil phase, dispersed, and then emulsified into the aqueous phase. An oil-in-water emulsified cosmetic composition having good usability is obtained, and the aqueous phase is emulsified after being added to and dispersed in the oil phase to obtain a stable water-in-oil emulsified cosmetic composition having good usability.

Powders that are preferably modified according to the present invention and then incorporated into cosmetics include, for example, silicic acid, silicic anhydride, magnesium silicate, talc, kaolin, mica, synthetic mica, bentonite, titanium-coated mica, oxychloride Bismuth, zirconium oxide, magnesium oxide, zinc oxide, titanium dioxide, calcium carbonate, magnesium carbonate, iron oxide,
Ultramarine, navy blue, chromium oxide, chromium hydroxide, zeolite,
Inorganic powder such as boron nitride, ceramic powder, calamine and carbon black, polyamide, polyester, polyethylene, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin,
Fluororesins, silicon resins, acrylic resins, melamine resins, epoxy resins, polycarbonate resins, divinylbenzene / styrene copolymers, and copolymers of two or more of the above compound monomers, celluloid, acetylcellulose, Organic powders of sugars, proteins, hard proteins, etc., Red No. 201, Red No. 202, Red No. 204, Red No. 205,
Red 220, Red 226, Red 228, Red 405, Orange 20
Organic pigments such as No. 3, orange No. 204, yellow No. 205, yellow No. 401 and blue No. 404, red No. 3, red No. 104, red No. 106, red
227, red 230, red 401, red 505, orange 205
No. 4, Yellow No. 5, Yellow No. 5, Yellow No. 202, Yellow No. 203, Green No. 3, and Blue No. 1 organic pigments such as zirconium, barium or aluminum lake, but are not necessarily limited thereto. .

The particle size of the powder is not particularly limited, but 0.001 ~ 200μ
In particular, fine particles having a particle size of 0.001 to 0.1 μm can be used by being covered with a uniform thin film.

Although the powder obtained in the first step is relatively stable per se, in order to stably incorporate it into a cosmetic containing water and / or a lower alcohol, a spacer compound in the second step is required. After the introduction of, a treatment by chemical modification in the third stage is required.

The powder obtained by introducing the olefin to the powder surface in the final stage is just hydrophobic, has no surface activity,
Compared to conventional powders treated with methylhydrogenpolysiloxane, in which residual Si-H groups were observed, it has remarkable stability, low reactivity, and does not change at all by contact with water or lower alcohol. Can be included in the product together with water and / or lower alcohol.

Therefore, the stability and usability of the cosmetic obtained by the present invention are good without causing deterioration, deterioration, etc. due to the blended powder.

According to the present invention, the powder coated with the silicone polymer having a pendant group can prevent generation of hydrogen from the Si-H portion even when blended in an aqueous system or an emulsified system.

Further, according to the present invention, a powder having high lipophilicity (or hydrophobicity) can be obtained by, for example, introducing a long-chain alkyl group to impart water repellency to the powder. Further, for example, by introducing a polyglycidyl group or a carboxyl group at the final stage, a powder having high hydrophilicity can be obtained.
Therefore, the modified powder according to the present invention can have extremely excellent dispersibility in a medium. For example, when the modified ultrafine titanium dioxide powder according to the present invention is blended in a sunscreen formulation, the dispersibility is improved. By being excellent, it is possible to obtain an ultraviolet ray blocking rate three to four times as high as that obtained by blending a conventional ultrafine titanium dioxide powder.

The amount of the surface-treated powder used in the present invention in the cosmetic is 0.01 to 90% by weight, preferably 0.1 to 8% by weight of the total amount of the cosmetic.
0% by weight.

The blending amount of water and / or lower alcohol is 5 to 90% by weight based on the total cosmetic amount.

Since the cosmetic containing the modified powder according to the present invention has no instability due to the powder, components commonly used in cosmetics in addition to the above essential components can be stably added.

For example, as a water phase component, humectants such as propylene glycol, dipropylene glycol, 1,3-butylene glycol, glycerin, maltitol, sorbitol, polyethylene glycol, sodium hyaluronate, and pyrrolidone carboxylate, petrolatum, lanolin, ceresin, and micro Solid and semi-solid oils such as crystallin wax, carnauba wax, candelilla wax, higher fatty acids and higher alcohols, squalane, liquid oil such as liquid paraffin, ester oil and triglyceride, coloring materials such as inorganic pigments, organic pigments and dyes , Other powders, cationic activators, anionic activators, nonionic activators, surfactants such as amphoteric activators, agents such as vitamin E, vitamin E acetate, astringents, antioxidants, preservatives , Fragrance, citric acid, sodium citrate, lactic acid, lactic acid Thorium, pH adjusting agents such as sodium secondary phosphate, thickeners such as organic modified montmorillonite, ultraviolet absorbers qualitative not to impair the effects of the present invention,
It can be blended within a quantitative range.

Among the modified solid materials according to the present invention, those in which a physiologically active substance is introduced in the final stage, the material and shape of the carrier can be freely selected, especially when the carrier is a powder, since the carrier does not aggregate during the manufacturing process. This is advantageous because it can be introduced at a high density.

In particular, the biologically active substance introduced into the ultrafine particle magnetic material according to the present invention has a higher introduction amount than the conventional method of directly treating with a silane coupler, coating the polymer and introducing a physiologically active substance there. Density.

The physiologically active substance in the present invention refers to, for example, an enzyme, a coenzyme, an enzyme inhibitor, a hormone, an antibiotic, a bactericide, an anticancer agent, an immunoreactive substance, or a substance having a significant effect on physiological functions such as animals and plants.

Examples of the enzyme include cholinesterase, cholesterol esterase, chlorophylase, esterases such as lecithinase, lipase, pectase, phosphatase, and sulfatase, amylase, hyaluronidase, heparinase, inulinase, lysozyme, isovertase, α-D-glucosidase, β-glucosidase, and α-glucosease. Carbohydrate hydrolases such as galactosidase, lactase, α-mannosidase, and thioglycosidase; phosphorylase, hexokinase, fructokinase, galactokinase, and enzymes relating to phosphorylation / phosphotransferase such as nucleoside kinase; ribonuclease, deoxyribonuclease, and nucleoside hydrolase; For nucleic acid metabolism such as nucleodeaminase, barbilase, uricase, etc. Enzymes, carboxypeptidase, leucine aminopeptidase, dehydropeptidase, pepsin, trypsin, chymotrypsin, papain, protease, arginase, urease, aspartase, glutaminase, transaminase urocanase, tyrosine oxidase, etc. Enzymes related to sugar metabolism such as transketolase, glyoxalase, carboxylase, crotonase, acetokinase, acetyl
In addition to enzymes related to fat metabolism, such as CoA transferase, deacylase, and choline acetylase, examples thereof include fumarase, malic enzyme, thiamine, hydrogenase, cytochrome, catalase, peroxidase, laccase, and luciferase.

Examples of the coenzyme include pyridoxal phosphate, nicotine adenine dinucleotide and the like. Examples of vitamins include vitamins A, B ₁ , B ₂ , B ₆ , nicotinic acid, pantothenic acid, folic acid, and vitamin B ₁₂ vitamins C, D, E, F, H, K, L, P, and the like.

Hormones include steroidal estrogen, estradiol, estriol, testosterone, cortisone, protein-based insulin, ACTH, and gonadotropin. As antibiotics, penicillins such as cloxacillin, cycloxacillin, flucloxacillin, piperacillin, cephaloridin, cephaloglysin, cefazolin, cefurazine, cephalosporins such as cefurazole, cephatrizine, streptomycin, kanamycin, valomycin ribosta Aminoglycosides such as mycin, amikacin and tobramycin; tetracyclines such as tetracycline, oxytetracycline, doxycycline and minocycline; macrolides such as erythromycin, spiramycin and midecamycin; other lincomycin, micamycin, gramicidin S, colistin, capreomycin, cyclo Serine, biaricin, mitomycin C, actinomycin, bleomycin Such as doxorubicin, and the like.

Fungicides include acrinol, acrylflavin, nitrofurazone, benzalkonium chloride, alkyldiaminoethylglycine hydrochloride and the like.

Anticancer agents include nitrogen mustard, nitramine, chlorambucil, cyclophosphamide, melphalan, uracil mustard, mannomustine, dopan,
Trenimon, busulfan, pipesulfan, etogluside, epoxypropidine, hexamethylmuramine, dibromomannitol, 6-mercaptopurine, uracil,
Cytarabine, thioteba, doxorubicin, neocarzinostan, hydroxyurea and the like.

Enzyme inhibitors include aprotinin, heparin and the like.

The immobilized enzyme is used for separation and purification of coenzymes and enzyme inhibitors, the immobilized coenzyme or enzyme inhibitor is used for separation and purification of enzymes, and the immobilized hormone is used for hormone receptors. The product on which the antigen is immobilized can be used for the separation and purification of antibodies.

Further, these specific adsorbents can be used for quantification of thyroid hormone, angiotensin and the like as clinical test materials for enzyme immunoassay and radioimmunoassay.

In addition, various diseases can be treated by removing various harmful substances from body fluids using those specific adsorbents.

〔Example〕

Next, the present invention will be described in more detail by way of examples, which do not limit the present invention.

Example 1 A spherical 5 was placed in a rotary double-cone type reaction vessel having a volume of 100 l (made of stainless steel and equipped with a heat retaining jacket).
10 kg of silica gel of μm was put therein. The temperature of the reaction tank and the processing liquid supply tank (stainless steel, with heat insulation jacket) with a volume of 10 liters directly connected to it are supplied to the heat insulation jacket from the heat medium heating tank by a circulation pump with a heat medium heated to 90 ° C. To 90 ° C. 5 kg of tetramethyltetrahydrogencyclotetrasiloxane in the processing tank
Was added, and nitrogen gas was supplied to the processing liquid supply tank at a rate of 2 l / min to bubble the processing liquid. An aggregator is attached to the reaction tank, and nitrogen gas is released therefrom so that unreacted treating agent can be recovered. The reaction tank was rotated for 1 minute at intervals of 10 minutes, and the operation of mixing silica gel in the reaction tank was repeated for 10 hours, and 12.5 kg of the treated powder was taken out. This treated powder showed remarkable hydrophobicity, and the linalool decomposability had disappeared.

Example 1.1 100 g of the silicone polymer-coated silica gel of Example 1 was placed in a 500 ml eggplant-shaped flask, and 10 mg of chloroplatinic acid and 100 m of allyl glycidyl ether were added thereto as a catalyst.
and 100 ml of isopropyl alcohol, and the mixture was heated and refluxed at 80 ° C. for 6 hours in an oil bath.
4) Filter using, wash with 1000 ml of acetone,
After degassing and drying, a silica gel with a spacer group added was obtained.

Example 1.1.1 50 g of the spacer-group-added silica gel obtained in Example 1.1 was placed in a 200-ml eggplant-shaped flask, and added thereto.
After adding 100 ml of 5N sulfuric acid and heating at 100 ° C. for 2 hours in an oil bath, the mixture is filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with a hydroxyl group. Was.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Heptane was flowed at a flow rate of 1 ml / min as a mobile phase, and a standard mixture of benzene, naphthalene, anthracene and 2,3-benzanthracene was injected.
Detection was performed at 4 nm, and a chromatogram was obtained. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.1.2 50 g of the spacer group-added silica gel obtained in Example 1.1 was placed in a 200 ml eggplant-shaped flask, and 1 m
ol / l sodium sulfite aqueous solution (100 ml)
After heating at 100 ° C for an hour, a glass filter (G-4)
After washing with water, deaeration and drying were performed to obtain a powder surface-modified with sodium sulfonate.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. 2M ammonium acetate-acetic acid (pH 4.6) as mobile phase
Was flowed at a flow rate of 1 ml / min, a standard mixture of lausyl, guanine, adenine and cytosine was injected and detected at 254 nm using a UV detector to obtain a chromatogram. As a result,
The retention time and the number of theoretical plates for each peak were as follows.

Example 1.1.3 50 g of the spacer-group-added silica gel obtained in Example 1.1 was placed in a 200-ml eggplant-shaped flask, and 100 ml of aqueous ammonia was added thereto. The mixture was heated at 80 ° C. for 4 hours in an oil bath. After filtration using G-4), washing with water, and deaeration drying, a powder surface-modified with amino groups was obtained.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Acrylonitrile / water (75/25) was flowed at a flow rate of 2 ml / min as a mobile phase, a standard mixture of fructose, glucose, saccharose, maltose and lactose was injected, and detected using an RI detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.1.4 50 g of the spacer-group-added silica gel obtained in Example 1.1 was placed in a 200 ml eggplant-shaped flask, and 100 ml of diethylamine was added thereto. The mixture was heated and refluxed at 55 ° C. for 4 hours in an oil bath. The resultant was filtered using G-4), further washed with 500 ml of acetone, and degassed and dried to obtain a powder surface-modified with diethylamino groups.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. As a mobile phase, 0.1 M phosphate-sodium-disodium phosphate / acetonitrile (80/20) was flowed at a flow rate of 1 ml / min, and a standard mixture of cystidin-phosphate, guanosine-phosphate and asenosin-phosphate was injected, and a UV detector was used. Was used for detection at 254 nm to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.1.5 50 g of the spacer-group-added silica gel obtained in Example 1.1 was placed in a 200-ml eggplant-shaped flask, and added thereto.
100 ml of a 5 mol / l hydrogen cyanide aqueous solution was added, and the mixture was heated and refluxed at 100 ° C. for 4 hours in an oil bath.
After filtration using 4), washing with water, and deaeration drying, a powder surface-modified with a cyano group was obtained.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Flowing ethanol / hexane (10/90) at a flow rate of 2 ml / min as a mobile phase, estrone, estradiol,
A standard mixture of hydrocortisone and dexamethasone was injected and detected at 254 nm using a UV detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.1.6 50 g of the spacer-group-added silica gel obtained in Example 1.1 was placed in a 200 ml eggplant-shaped flask, to which 150 g of monoglycerin and 0.1 g of zinc zinc tetrafluoride were added, and the mixture was heated at 100 ° C. for 4 hours in an oil bath. After heating and refluxing, filtration using a glass filter (G-4), washing with water, and deaeration drying were performed to obtain a powder surface-modified with monoglycerin.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 1.1.7 50 g of the spacer-group-added silica gel obtained in Example 1.1 was placed in a 200-ml eggplant-shaped flask, and 100 ml of diglycerin and 0.1 g of zinc boron fluoride were added thereto. After heating under reflux, the mixture was filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with diglycerin.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 1.2 100 g of the silicone polymer-coated silica gel of Example 1 was placed in a 500 ml eggplant-shaped flask, and placed in an oil bath containing 10 mg of chloroplatinic acid, 100 ml of glycerol-α-monoallyl ether and 100 ml of isopropyl alcohol as a catalyst. After heating and refluxing at 80 ° C. for a time, the mixture was filtered using a glass filter (G-4), further washed with acetone, and degassed and dried to obtain a spacer group-added silica gel.

Example 1.1.1.1 Surface Modified Powder Obtained in Example 1.1 or Spacer Group-Added Silica Gel 5 Obtained in Example 1.2
0 g was placed in a 200 ml eggplant-shaped flask, and 100 ml of 1.5 mol / l sodium periodate aqueous solution (pH 8.5) and 1.5 g of potassium permanganate were added thereto, and the mixture was heated and refluxed at 100 ° C. for 2 hours in an oil bath. After filtration using a glass filter (G-4), washing with water, and deaeration drying, a powder having a carboxy group surface-modified was obtained.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. As a mobile phase, 0.025% phosphoric acid-50 mM monopotassium phosphate was flowed at a flow rate of 2 ml / min, a standard mixture of norepinephrine, epinephrine and dopamine was injected, and the mixture was detected at 254 nm using a UV detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.1.2.1 Surface-modified powder 50 obtained in Example 1.1.2
g in a 200 ml eggplant-shaped flask, into which 0.1N hydrochloric acid 100m
After heating and refluxing at 100 ° C. for 2 hours in an oil bath, the mixture was filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with sulfone groups. .

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 5 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. A lithium citrate buffer as a mobile phase and a ninhydrin reagent as a reaction reagent are respectively flowed at a flow rate of 0.5 ml / min, a standard mixture of phosphoserine, urea, and aspartic acid is injected, and the chromatogram is detected at 570 nm using a VIS detector. I got As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.1.3.1 Surface modified powder 10 obtained in Example 1.1.3
g in a 100 ml eggplant-shaped flask, and well dispersed in 50 ml of a phosphate buffer solution (pH 3.0) to give 1-ethyl-3- (3
-Dimethylaminopropyl) carbodiimide hydrochloride (1 g) and lipase (1 g) were added, and the mixture was allowed to stand at room temperature for 24 hours. Then, the mixture was filtered using a glass filter (G-4), and further filtered with 500 m of water.
After washing with l, degassing and drying were performed to obtain lipase-bonded silica gel.

Example 1.1.4.1 Surface-modified powder 50 obtained in Example 1.1.4
g into a 200 ml eggplant-shaped flask, and add ethyl iodide
After adding 100 ml and heating to reflux at 80 ° C. for 2 hours in an oil bath while flowing nitrogen gas at 100 ml / min, a glass filter (G-
4) Filter using and wash with 500 ml of acetone,
The powder was deaerated and dried to obtain a powder surface-modified with a quaternary ammonium salt.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. 1mM phthalic acid (pH3.4) as mobile phase, flow rate 1.5ml / mi
Flowed at n, a standard mixture of acetic acid, lactic acid, succinic acid and formic acid was injected, detected using an EC detector, and a chromatogram was obtained. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.3 100 g of the silicone polymer-coated silica gel of Example 1 was placed in a 500-ml eggplant-shaped flask, and placed in an oil bath containing 10 mg of chloroplatinic acid, 100 ml of allyl alcohol and 100 ml of isopropyl alcohol as a catalyst for 4 hours.
After heating under reflux at 0 ° C., the solution was filtered using a glass filter (G-4), further washed with 1000 ml of acetone, and degassed and dried to obtain a silica gel with a spacer group added.

Example 1.3.1 50 g of the spacer group-added silica gel obtained in Example 1.3 was placed in a 200 ml eggplant-shaped flask, and 1.
100 ml of 5 mol / l sodium periodate aqueous solution (pH 8.5) and 1.5 g of potassium permanganate are added, and the mixture is placed in an oil bath for 2 hours.
After heating at ℃, it was filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with a carboxy group.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. As a mobile phase, 0.025% phosphoric acid-50 mM monopotassium phosphate was flowed at a flow rate of 1 ml / min, a standard mixture of norepinephrine, epinephrine and dopamine was injected, and the mixture was detected at 254 nm using a UV detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.3.2 50 g of the spacer-group-added silica gel obtained in Example 1.3 was placed in a 200-ml eggplant-shaped flask, 100 nl of thionyl chloride was added thereto, and the mixture was stirred at room temperature for 24 hours.
The solution was filtered using a glass filter (G-4), further washed with 500 ml of acetone, and degassed and dried to obtain a powder surface-modified with a chloro group.

Example 1.4 100 g of the silicone polymer-coated silica gel of Example 1 was placed in a 500 ml eggplant-shaped flask, to which 10 mg of chloroplatinic acid, 100 ml of allyl chloride and 100 ml of chloroform were added as a catalyst, and heated at 60 ° C. for 4 hours in an oil bath under reflux. After that, the mixture was filtered using a glass filter (G-4), further washed with 1000 ml of acetone, and degassed and dried to obtain a spacer group-added silica gel.

Example 1.3.2.1 Surface-modified powder obtained in Example 1.3.2,
Alternatively, 50 g of the spacer group-added silica gel obtained in Example 1.4 was placed in a 200 ml eggplant-shaped flask, and nitrogen chloride was added thereto.
After adding 50 ml, 50 ml of dichloroethane and 1 g of aluminum chloride and reacting at -10 ° C for 1 hour, the mixture was filtered using a glass filter (G-4), further washed with 500 ml of acetone, degassed and dried, and amino groups were removed. A surface-modified powder was obtained.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Acrylonitrile / water (75/25) was flowed at a flow rate of 2 ml / min as a mobile phase, a standard mixture of fructose, glucose, saccharose, maltose, and lactose was injected, detected using an RI detector, and a chromatogram was obtained. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.3.2.2 Surface-modified powder obtained in Example 1.3.2,
Alternatively, 50 g of the spacer group-added silica gel obtained in Example 1.4 was placed in a 200-ml eggplant-shaped flask, 100 ml of 1 mol / l sodium sulfite was added thereto, and the mixture was heated under reflux at 100 ° C. for 5 hours. After washing with water, deaeration and drying were performed to obtain a powder surface-modified with sodium sulfonate.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. 2M ammonium acetate-acetic acid (pH 4.6) as mobile phase
Was flowed at a flow rate of 1 ml / min, a standard mixture of uracil, guanine, adenine and cytosine was injected and detected at 254 nm using a UV detector to obtain a chromatogram. As a result,
The retention time and the number of theoretical plates for each peak were as follows.

Example 1.3.2.3 Surface-modified powder obtained in Example 1.3.2,
Alternatively, 50 g of the spacer group-added silica gel obtained in Example 1.4 was placed in a 200-ml eggplant-shaped flask, 100 ml of a 1 mol / l aqueous solution of hydrogen cyanide was added thereto, and the mixture was heated under reflux at 100 ° C. for 6 hours. And filtered using
After washing with water, deaeration and drying were performed to obtain a powder surface-modified with a cyano group.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Flowing ethanol / hexane (10/90) at a flow rate of 2 ml / min as a mobile phase, estrone, estradiol,
A standard mixture of hydrocortisone and dexamethasone was injected and detected at 254 nm using a UV detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.5 100 g of the silicone polymer-coated silica gel of Example 1 was placed in a 500 ml eggplant-shaped flask, and 10 mg of chloroplatinic acid and sodium allyl sulfonate were added thereto as a catalyst.
After adding 50 g and 200 ml of dimethyl sulfoxide, the mixture was heated and refluxed at 120 ° C. for 4 hours in an oil bath, filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a silica gel with a spacer group added thereto. Obtained.

Example 1.5.1 Surface modified powder obtained in Example 1.3.2.2,
Alternatively, 50 g of the spacer group-added silica gel obtained in Example 1.5 was placed in a 200 ml eggplant-shaped flask, and 0.1N hydrochloric acid was added thereto.
After adding 100 ml and heating to reflux in an oil bath at 100 ° C. for 2 hours,
The mixture was filtered using a glass filter (G-4), washed with 500 ml of acetone, deaerated and dried to obtain a powder surface-modified with a sulfone group.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 5 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. A lithium citrate buffer as a mobile phase and a ninhydrin reagent as a reaction reagent are respectively flowed at a flow rate of 0.5 ml / min, a standard mixture of phosphoserine, urea, and aspartic acid is injected, and the chromatogram is detected at 570 nm using a VIS detector. I got As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.6 100 g of the silicone polymer-coated silica gel of Example 1 was placed in a 500 ml eggplant-shaped flask, to which 10 mg of tributylamine chloroplatinate, 100 ml of allyl phenyl ether and 100 ml of toluene were added as catalysts and placed in an oil bath for 4 hours. After heating under reflux at ℃, the solution was filtered using a glass filter (G-4), washed with 1000 ml of acetone, and degassed and dried to obtain silica gel with a spacer group added.

Example 1.6.1 50 g of the spacer-group-added silica gel obtained in Example 1.6 was placed in a 200 ml eggplant-shaped flask, to which 0.5 g of potassium-t-butoxide and 100 ml of pentane were added, and carbon dioxide was further added at a flow rate of 50 ml / min. After reacting at room temperature for 5 hours while flowing, the mixture was filtered using a glass filter (G-4), washed with 500 ml of acetone, and degassed and dried to obtain a powder surface-modified with a carboxy group.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. 0.025% H ₃ PO ₄ -50mM KH ₂ PO ₄ as mobile phase, flow rate 1m
flow at 1 / min, inject a standard mixture of norepinephrine, epinephrine and dopamine, and use a UV detector for 25
Detection was performed at 4 nm, and a chromatogram was obtained. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.6.1.1 Surface-modified powder 50 obtained in Example 1.6.1
g in a 200 ml eggplant-shaped flask, 3.0 g of diisobutylaluminum hydride and 100 ml of dioxane were added thereto and reacted at 0 ° C. for 6 hours.
4) Filter using and wash with 500 ml of acetone,
Degassed and dried. After drying sufficiently, add 50 g of this powder to 200
100 ml of toluene flask and 100 g of toluene and 0.5 g of iodine.Add ammonia gas at a flow rate of 200 m.
After reacting at room temperature for 4 hours while flowing at l / min, the mixture was filtered using a glass filter (G-4), and further acetone
The powder was washed with 500 ml, degassed and dried to obtain a powder surface-modified with a cyano group.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Flowing ethanol / hexane (10/90) at a flow rate of 2 ml / min as a mobile phase, estrone, estradiol,
A standard mixture of hydrocortisone and dexamethasone was injected and detected at 254 nm using a UV detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.6.2 50 g of the spacer-group-added silica gel obtained in Example 1.6 was placed in a 200-ml eggplant-shaped flask, 50 ml of concentrated nitric acid and 50 ml of concentrated sulfuric acid were added thereto, and the mixture was reacted at room temperature for 2 hours. After filtration using -4) and washing with water, deaeration and drying were performed. After drying sufficiently, this powder 50
g into a 200 ml eggplant-shaped flask and add 100 ml of distilled water
And 0.5 g of iron powder were added thereto, and the mixture was heated and refluxed at 100 ° C. for 6 hours in an oil bath, filtered using a glass filter (G-4), washed with water, degassed and dried, and then subjected to surface modification with a cyano group. I got a body.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Acrylonitrile / water (75/25) was flowed at a flow rate of 2 ml / min as a mobile phase, a standard mixture of fructose, glucose, saccharose, maltose and lactose was injected, and detected using an RI detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.6.3 50 g of the spacer-group-added silica gel obtained in Example 1.6 was placed in a 200 ml eggplant-shaped flask, and 5 g of the flask was added thereto.
After adding 100 ml of fuming sulfuric acid and heating to reflux in an oil bath at 100 ° C. for 4 hours, the mixture was filtered using a glass filter (G-4).
After washing with water, the powder was degassed and dried to obtain a powder surface-modified with sulfone groups.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 5 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. A lithium citrate buffer as a mobile phase and a ninhydrin reagent as a reaction reagent are respectively flowed at a flow rate of 0.5 ml / min, a standard mixture of phosphoserine, urea, and aspartic acid is injected, and the chromatogram is detected at 570 nm using a VIS detector. I got As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.6.3.1 Surface-modified powder 50 obtained in Example 1.6.3
g in a 200 ml eggplant-shaped flask, 100 ml of a 1 mol / l aqueous solution of calcium hydroxide was added thereto, and the mixture was heated and refluxed at 1000 ° C. for 4 hours in an oil bath. Thereafter, deaeration drying was performed. After drying sufficiently,
50 g of this powder is placed in a 200 ml eggplant-shaped flask, and 1 m
ol / l sodium carbonate aqueous solution (100 ml) was added, and the mixture was heated and refluxed at 100 ° C. for 6 hours in an oil bath.
After filtration using 4) and washing with water, deaeration was performed to obtain a powder surface-modified with sodium sulfonate.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. 2M ammonium acetate-acetic acid (pH 4.6) as mobile phase
Was flowed at a flow rate of 1 ml / min, a standard mixture of uracil, guanine, adenine and cytosine was injected and detected at 254 nm using a UV detector to obtain a chromatogram. As a result,
The retention time and the number of theoretical plates for each peak were as follows.

Example 1.7 100 g of the silicone polymer-coated silica gel of Example 1 was placed in a 500 ml eggplant-shaped flask, to which 10 mg of chloroplatinic acid, 100 ml of styrene, 0.5 g of para-t-butylcatechol and 100 ml of toluene were added as a catalyst, and the mixture was placed in an oil bath. After heating under reflux at 110 ° C. for 4 hours, the mixture was filtered using a glass filter (G-4), further washed with 1000 ml of acetone, and degassed and dried to obtain a silica gel to which a spacer group was added.

Example 1.7.1 50 g of the spacer-group-added silica gel obtained in Example 1.7 was placed in a 200 ml eggplant-shaped flask, to which 0.5 g of potassium-t-butoxide and 100 ml of pentane were added, and carbon dioxide was further added at a flow rate of 50 ml / min. After reacting at room temperature for 5 hours while flowing, the mixture was filtered using a glass filter (G-4), washed with 500 ml of acetone, and degassed and dried to obtain a powder surface-modified with a carboxy group.

Using a packer and a pump, 3 g of the obtained multi-stage surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography.

0.025% H ₃ PO ₄ -50 mM KH ₂ PO ₄ as mobile phase, flow rate 1 ml / mi
n, inject a standard mixture of norepinephrine, epinephrine and dopamine, and use a UV detector at 254 nm
And a chromatogram was obtained. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.7.1.1 Surface-modified powder 50 obtained in Example 1.7.1
g in a 200 ml eggplant-shaped flask, 3.0 g of diisobutylaluminum hydride and 100 ml of dioxane were added thereto and reacted at 0 ° C. for 6 hours.
4) Filter using and wash with 500 ml of acetone,
Degassed and dried. After drying sufficiently, add 50 g of this powder to 200
100 ml of toluene flask and 100 g of toluene and 0.5 g of iodine.Add ammonia gas at a flow rate of 200 m.
After reacting at room temperature for 4 hours while flowing at l / min, the mixture was filtered using a glass filter (G-4), and further acetone
The powder was washed with 500 ml, degassed and dried to obtain a powder surface-modified with a cyano group.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Flowing ethanol / hexane (10/90) at a flow rate of 2 ml / min as a mobile phase, estrone, estradiol,
A standard mixture of hydrocortisone and dexamethasone was injected and detected at 254 nm using a UV detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.7.2 50 g of the spacer-group-added silica gel obtained in Example 1.7 was placed in a 200 ml eggplant-shaped flask, 50 ml of concentrated nitric acid and 50 ml of concentrated sulfuric acid were added thereto, and the mixture was reacted at room temperature for 2 hours. After filtration using -4) and washing with water, deaeration and drying were performed. After drying sufficiently, this powder 50
g in a eggplant-shaped flask, and add 150 ml of distilled water
And 0.5 g of iron powder was added thereto, and the mixture was heated and refluxed at 100 ° C. for 6 hours in an oil bath, and then filtered using a glass filter (G-4.
After washing with water, deaeration and drying were performed to obtain a powder surface-modified with amino groups.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Acrylonitrile / water (75/25) was flowed at a flow rate of 2 ml / min as a mobile phase, a standard mixture of fructose, glucose, saccharose, maltose and lactose was injected, and detected using an RI detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.7.3 50 g of the spacer group-added silica gel obtained in Example 1.7 was placed in a 200 ml eggplant-shaped flask, and 5 g of the flask was added thereto.
After adding 100 ml of fuming sulfuric acid and heating to reflux in an oil bath at 100 ° C. for 4 hours, the mixture was filtered using a glass filter (G-4).
After washing with water, deaeration and drying were performed to obtain a powder surface-modified with amino groups.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 5 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. A lithium citrate buffer as a mobile phase and a ninhydrin reagent as a reaction reagent are respectively flowed at a flow rate of 0.5 ml / min, a standard mixture of phosphoserine, urea, and aspartic acid is injected, and the chromatogram is detected at 570 nm using a VIS detector. I got As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.7.3.1 Surface-modified powder 50 obtained in Example 1.7.3
g in a 200 ml eggplant-shaped flask, 100 ml of a 1 mol / l aqueous solution of calcium hydroxide was added thereto, and the mixture was heated and refluxed at 100 ° C. for 4 hours in an oil bath, then filtered using a glass filter (G-4), and washed with water. Thereafter, deaeration drying was performed. After drying sufficiently, take 50 g of this powder in a 200 ml eggplant-shaped flask, and add 1 mol
100 ml of an aqueous solution of sodium carbonate / l for 6 hours in an oil bath
After heating and refluxing at 00 ° C., the mixture was filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with sodium sulfonate.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. 2M ammonium acetate-acetic acid (pH 4.6) as mobile phase
Was flowed at a flow rate of 1 ml / min, a standard mixture of uracil, guanine, adenine and cytosine was injected and detected at 254 nm using a UV detector to obtain a chromatogram. As a result,
The retention time and the number of theoretical plates for each peak were as follows.

Example 1.8 100 g of the silicone polymer-coated silica gel of Example 1 and aqueous ammonia were placed in a desiccator at 80 ° C.
Heat for 4 hours. This is washed with an aqueous ethanol solution containing 0.1N hydrochloric acid.

100 g of this powder was placed in a 500 ml eggplant-shaped flask, 50 g of γ-glycidoxypropyltrimethoxysilane and 200 ml of water were added, and the mixture was stirred at room temperature for 2 hours, and then filtered using a glass filter (G-4). After washing with water, degassed and dried to obtain a silica gel having a spacer group added thereto.

Example 1.8.1 50 g of the spacer-group-added silica gel obtained in Example 1.8 was placed in a 200-ml eggplant-shaped flask, and added to the flask.
After adding 100 ml of 5N sulfuric acid and heating at 100 ° C. for 2 hours in an oil bath, the mixture is filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with a hydroxyl group. Was.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Heptane was flowed at a flow rate of 1 ml / min as a mobile phase, and a standard mixture of benzene, naphthalene, anthracene and 2,3-benzanthracene was injected.
Detection was performed at 4 nm, and a chromatogram was obtained. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.8.2 50 g of the spacer group-added silica gel obtained in Example 1.8 was placed in a 200 ml eggplant-shaped flask, and 1 m
ol / l sodium sulfite aqueous solution (100 ml)
After heating at 80 ° C. for an hour, the mixture was filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with sodium sulfonate.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. 2M ammonium acetate-acetic acid (pH 4.6) as mobile phase
Was flowed at a flow rate of 1 ml / min, a standard mixture of uracil, guanine, adenine and cytosine was injected, and detected at 254 nm using a UV detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.8.3 50 g of the spacer-group-added silica gel obtained in Example 1.8 was placed in a 200-ml eggplant-shaped flask, and 100 ml of aqueous ammonia was added thereto. The mixture was heated at 80 ° C. for 4 hours in an oil bath. After filtration using G-4), washing with water, and deaeration drying, a powder surface-modified with amino groups was obtained.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Acrylonitrile / water (75/25) was flowed at a flow rate of 2 ml / min as a mobile phase, a standard mixture of fructose, glucose, saccharose, maltose and lactose was injected, and detected using an RI detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.8.4 50 g of the spacer group-added silica gel obtained in Example 1.8 was placed in a 200 ml eggplant-shaped flask, and 100 ml of diethylamine was added thereto. The mixture was heated and refluxed at 55 ° C. for 4 hours in an oil bath, and then filtered with a glass filter ( The resultant was filtered using G-4), further washed with 500 ml of acetone, degassed and dried to obtain a powder surface-modified with diethylamine.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. As a mobile phase, 0.1 M monosodium phosphate-disodium phosphate / acetonitrile (80/20) is flowed at a flow rate of 1 ml / min, and a standard mixture of cystidine monophosphate, guanosine monophosphate and adenosine monophosphate is injected. Detection was performed at 254 nm using a UV detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.8.5 50 g of the spacer-group-added silica gel obtained in Example 1.8 was placed in a 200-ml eggplant-shaped flask, and added thereto.
150 ml of a 5 mol / l hydrogen cyanide aqueous solution was added, and the mixture was heated and refluxed at 100 ° C. for 4 hours in an oil bath.
After filtration using 4), washing with water, and deaeration drying, a powder surface-modified with a cyano group was obtained.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Flowing ethanol / hexane (10/90) at a flow rate of 2 ml / min as a mobile phase, estrone, estradiol,
A standard mixture of hydrocortisone and dexamethasone was injected and detected at 254 nm using a UV detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.8.6 50 g of the spacer-group-added silica gel obtained in Example 1.8 was placed in a 200-ml eggplant-shaped flask, and 100 g of monoglycerin and 0.1 g of zinc zinc tetrafluoride were added thereto. After heating and refluxing, filtration using a glass filter (G-4), washing with water, and deaeration drying were performed to obtain a powder surface-modified with monoglycerin.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 1.8.7 50 g of the spacer-group-added silica gel obtained in Example 1.8 was placed in a 200-ml eggplant-shaped flask, to which 100 ml of diglycerin and 0.1 g of zinc zinc tetrafluoride were added, and the mixture was heated at 100 ° C. for 4 hours in an oil bath. After heating under reflux, the mixture was filtered using a glass filter (G-4), washed with water, degassed and dried to obtain a powder surface-modified with diglycerin.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 1.8.1.1 Surface-modified powder 50 obtained in Example 1.8.1
g was placed in a 200 ml eggplant-shaped flask, and 100 ml of a 1.5 mol / l sodium periodate aqueous solution (pH 8.5) and 1.5 g of potassium permanganate were added thereto, and heated at 100 ° C. for 2 hours in an oil bath. The mixture was filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with a carboxy group.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. As a mobile phase, 0.025% phosphoric acid-50 mM monopotassium phosphate was flowed at a flow rate of 1 ml / min, a standard mixture of norepinephrine, epinephrine and dopamine was injected, and the mixture was detected at 254 nm using a UV detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.8.2.1 Surface-modified powder 50 obtained in Example 1.8.2
g in a 200 ml eggplant-shaped flask, into which 0.1N hydrochloric acid 100m
After heating and refluxing at 100 ° C. for 2 hours in an oil bath, the mixture was filtered using a glass filter (G-4), washed with water, degassed and dried to obtain a powder surface-modified with sulfonic acid. .

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 5 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. A lithium citrate buffer as a mobile phase and a ninhydrin reagent as a reaction reagent are respectively flowed at a flow rate of 0.5 ml / min, a standard mixture of phosphoserine, urea, and aspartic acid is injected, and the chromatogram is detected at 570 nm using a VIS detector. I got As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.8.3.1 Surface-modified powder 10 obtained in Example 1.8.3
g in a 100 ml eggplant-shaped flask, and well dispersed in 50 ml of a phosphate buffer solution (pH 3.0) to give 1-ethyl-3- (3
-Dimethylaminopropyl) carbodiimide hydrochloride (1 g) and lipase (1 g) were added, and the mixture was allowed to stand at room temperature for 24 hours. Then, the mixture was filtered using a glass filter (G-4), and further filtered with 500 m of water.
After washing with l, degassing and drying were performed to obtain lipase-bonded silica gel.

Example 1.8.4.1 Surface-modified powder 50 obtained in Example 1.8.4
g into a 200 ml eggplant-shaped flask, and add ethyl iodide
After adding 100 ml and heating to reflux at 80 ° C. for 2 hours in an oil bath while flowing nitrogen gas at 100 ml / min, a glass filter (G-
4) Filter using and wash with 500 ml of acetone,
The powder was deaerated and dried to obtain a powder surface-modified with a quaternary ammonium salt.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. 1mM phthalic acid (pH3.4) as mobile phase, flow rate 1.5ml / mi
Flowed at n, a standard mixture of acetic acid, lactic acid, succinic acid and formic acid was injected, detected using an EC detector, and a chromatogram was obtained. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.9 100 g of the silicone polymer-coated silica gel of Example 1 and aqueous ammonia were placed in a desiccator at 80 ° C.
Heat for 4 hours. This is washed with an aqueous ethanol solution containing 0.1N hydrochloric acid.

100 g of this powder was placed in a 500 ml eggplant-shaped flask, to which was added 30 g of 3-cyanopropyldimethylchlorosilane and 300 ml of toluene, and the mixture was heated and refluxed at 110 ° C. for 6 hours in an oil bath, and then used with a glass filter (G-4). Filter
Further, the resultant was washed with 1000 ml of acetone, deaerated and dried to obtain a silica gel having a spacer group added thereto.

Example 1.9.1 50 g of the surface-modified powder obtained in Example 1.9 was used.
Take in a 200 ml eggplant-shaped flask, add 100 ml of 1.5 mol / l sodium periodate aqueous solution (pH 8.5) and 1.5 g of potassium permanganate, and heat in an oil bath at 100 ° C. for 2 hours. After filtration using (G-4) and washing with water, deaeration was performed to obtain a powder surface-modified with a carboxy group.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. As a mobile phase, 0.025% phosphoric acid-50 mM monopotassium phosphate was flowed at a flow rate of 1 ml / min, a standard mixture of norepinephrine, epinephrine and dopamine was injected, and the mixture was detected at 254 nm using a UV detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.10 100 g of the silicone polymer-coated silica gel of Example 1 and aqueous ammonia were placed in a desiccator at 80 ° C.
Heat for 4 hours. This is washed with an aqueous ethanol solution containing 0.1N hydrochloric acid.

100 g of this powder was placed in a 500 ml eggplant-shaped flask, and 30 g of aminopropyltrimethoxysilane and 200 ml of water were added thereto.
After stirring at room temperature for 2 hours, the mixture was filtered using a glass filter (G-4), washed with water, and then degassed and dried to obtain a spacer group-added silica gel.

Example 1.10.1 10 g of the surface-modified powder obtained in Example 1.10
Was placed in a 100 ml eggplant-shaped flask, and dispersed well in 50 ml of a phosphate buffer (pH 3.0), and 1-ethyl-3- (3
-Dimethylaminopropyl) carbodiimide hydrochloride (1 g) and lipase (1 g) were added, and the mixture was allowed to stand at room temperature for 24 hours. Then, the mixture was filtered using a glass filter (G-4), and further filtered with 500 m of water.
After washing with l, degassing and drying were performed to obtain lipase-bonded silica gel.

Example 1.11 100 g of the silicone polymer-coated silica gel of Example 1 and aqueous ammonia were placed in a desiccator at 80 ° C.
Heat for 4 hours. This is washed with an aqueous ethanol solution containing 0.1N hydrochloric acid.

100 g of this powder was placed in a 500 ml eggplant-shaped flask, and 30 g of γ-chloropropyltrimethoxysilane and water 2
After adding 00 ml and stirring at room temperature for 2 hours, the mixture was filtered using a glass filter (G-4), washed with water, and then degassed and dried to obtain a silica gel to which a spacer group was added.

Example 1.11.1. 50 g of the spacer-group-added silica gel obtained in Example 1.11 was placed in a 200 ml eggplant-shaped flask, and 50 ml of nitrogen chloride, 100 ml of dichloroethane and 1 g of aluminum chloride were added thereto, and the mixture was reacted at -10 ° C. for 1 hour. Thereafter, the mixture was filtered using a glass filter (G-4), further washed with 500 ml of acetone, and degassed and dried to obtain a powder surface-modified with an amino group.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Acetonitrile / water (75/25) flow rate 2 as mobile phase
The mixture was flowed at ml / min, a standard mixture of fructose, glucose, saccharose, maltose, and lactose was injected, detected using an RI detector, and a chromatogram was obtained.
As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.11.2 50 g of the spacer group-added silica gel obtained in Example 1.11 was placed in a 200 ml eggplant-shaped flask, and
100 mol of 1 mol / l sodium sulfite was added, and the mixture was heated and refluxed at 100 ° C. for 5 hours, filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with sodium sulfonate. Obtained.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. 2M ammonium acetate-acetic acid (pH 4.6) as mobile phase
Was flowed at a flow rate of 1 ml / min, a standard mixture of uracil, guanine, adenine and cytosine was injected and detected at 254 nm using a UV detector to obtain a chromatogram. As a result,
The retention time and the number of theoretical plates for each peak were as follows.

Example 1.11.2.1 Surface-modified powder obtained in Example 1.11.2
Transfer 50 g to a 200 ml eggplant-shaped flask and add 0.1N hydrochloric acid 10
After adding 0 ml and heating and refluxing at 100 ° C. for 2 hours in an oil bath, the mixture was filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with a sulfone group. .

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 5 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. A lithium citrate buffer as a mobile phase and a ninhydrin reagent as a reaction reagent are respectively flowed at a flow rate of 0.5 ml / min, a standard mixture of phosphoserine, urea, and aspartic acid is injected, and the chromatogram is detected at 570 nm using a VIS detector. I got As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.11.3 50 g of the spacer-group-added silica gel obtained in Example 1.11 was placed in a 200-ml eggplant-shaped flask.
100 ml of a 1 mol / l hydrogen cyanide aqueous solution was added, and the mixture was heated and refluxed at 100 ° C. for 6 hours, filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with a cyano group. Was.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Flowing ethanol / hexane (10/90) at a flow rate of 2 ml / min as a mobile phase, estrone, estradiol,
A standard mixture of hydrocortisone and dexamethasone was injected and detected at 254 nm using a UV detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.12 100 g of the silicone polymer-coated silica gel of Example 1 and aqueous ammonia were placed in a desiccator at 80 ° C.
Heat for 4 hours. This is washed with an aqueous ethanol solution containing 0.1N hydrochloric acid.

100 g of this powder was placed in a 500 ml eggplant-shaped flask, 30 g of (N, N-diethyl-3-aminopropyl) trimethoxysilane and 200 ml of water were added, and the mixture was stirred at room temperature for 2 hours. ) And filtered
After washing with water, deaeration and drying were performed to obtain silica gel with a spacer group added.

Example 1.12.1 50 g of surface-modified powder obtained in Example 1.12.
Into a 200 ml eggplant-shaped flask, and add ethyl iodide 1
Then, the mixture was heated and refluxed at 80 ° C. for 2 hours in an oil bath while flowing nitrogen gas at 100 ml / min.
4) Filter using and wash with 500 ml of acetone,
The powder was deaerated and dried to obtain a powder surface-modified with a quaternary ammonium salt.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. 1mM phthalic acid (pH3.4) as mobile phase, flow rate 1.5ml / mi
Flowed at n, a standard mixture of acetic acid, lactic acid, succinic acid and formic acid was injected, detected using an EC detector, and a chromatogram was obtained. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.13 100 g of the silicone polymer-coated silica gel of Example 1 and aqueous ammonia were placed in a desiccator at 80 ° C.
Heat for 4 hours. This is washed with an aqueous ethanol solution containing 0.1N hydrochloric acid.

100 g of this powder was placed in a 500 ml eggplant-shaped flask, 30 g of phenethyltrimethoxysilane and 200 ml of water were added thereto, and the mixture was stirred at room temperature for 2 hours.
After filtration using 4) and washing with water, degassing and drying were performed to obtain a silica gel with a spacer group added.

Example 1.13.1 50 g of the spacer-group-added silica gel obtained in Example 1.13 was placed in a 200 ml eggplant-shaped flask, to which 0.5 g of potassium-t-butoxide and 100 ml of pentane were added, and carbon dioxide was further added at a flow rate of 50 ml / min. After reacting at room temperature for 5 hours while flowing, the mixture was filtered using a glass filter (G-4), washed with 500 ml of acetone, and degassed and dried to obtain a powder surface-modified with a carboxy group.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. As a mobile phase, 0.025% phosphoric acid-50 mM monopotassium phosphate was flowed at a flow rate of 1 ml / min, a standard mixture of noelpinephrine, epinephrine and dopamine was injected, and the mixture was detected at 254 nm using a UV detector to obtain a chromatogram. Was. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.13.1.1 Surface-modified powder obtained in Example 1.13.1
50 g was placed in a 200 ml eggplant-shaped flask, and 3.0 g of diisobutylaluminum hydride and 100 ml of dioxane were added thereto and reacted at 0 ° C. for 6 hours.
4) Filter using and wash with 500 ml of acetone,
Degassed and dried. After drying sufficiently, add 50 g of this powder to 200
100 ml of toluene flask and 100 g of toluene and 0.5 g of iodine.Add ammonia gas at a flow rate of 200 m.
After reacting at room temperature for 4 hours while flowing at l / min, the mixture was filtered using a glass filter (G-4), and further acetone
The powder was washed with 500 ml, degassed and dried to obtain a powder surface-modified with a cyano group.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Flowing ethanol / hexane (10/90) at a flow rate of 2 ml / min as a mobile phase, estrone, estradiol,
A standard mixture of hydrocortisone and dexamethasone was injected and detected at 254 nm using a UV detector to obtain a chromatogram. As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.13.2 50 g of the spacer-group-added silica gel obtained in Example 1.13. Was placed in a 200 ml eggplant-shaped flask, 50 ml of concentrated nitric acid and 50 ml of concentrated sulfuric acid were added thereto, and the mixture was reacted at room temperature for 2 hours. After filtration using G-4) and washing with water, deaeration and drying were performed. After drying sufficiently, 50 g of this powder was placed in a 200 ml eggplant-shaped flask, and concentrated hydrochloric acid was added thereto.
After adding 50 ml and 0.5 g of iron powder, the mixture was heated and refluxed at 100 ° C. for 6 hours in an oil bath, filtered using a glass filter (G-4), washed with water, degassed and dried, and surface-modified with amino groups. A powder was obtained.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. Acetonitrile / water (75/25) flow rate 2 as mobile phase
The mixture was flowed at ml / min, a standard mixture of fructose, glucose, saccharose, maltose, and lactose was injected, detected using an RI detector, and a chromatogram was obtained.
As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.13.3 50 g of the spacer-group-added silica gel obtained in Example 1.13 was placed in a 200 ml eggplant-shaped flask, 100 ml of 5% fuming sulfuric acid was added, and the mixture was heated and refluxed at 100 ° C. for 4 hours in an oil bath. The mixture was filtered using a filter (G-4), washed with water, and then degassed and dried to obtain a powder surface-modified with a sulfone group.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 5 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. A lithium citrate buffer as a mobile phase and a ninhydrin reagent as a reaction reagent are respectively flowed at a flow rate of 0.5 ml / min, a standard mixture of phosphoserine, urea, and aspartic acid is injected, and the chromatogram is detected at 570 nm using a VIS detector. I got As a result, the retention time of each peak and the number of theoretical plates were as follows.

Example 1.13.3.1 Surface-modified powder obtained in Example 1.13.3
50 g was placed in a 200 ml eggplant-shaped flask, and 100 ml of a 1 mol / l sodium carbonate aqueous solution was added thereto. The mixture was heated and refluxed at 100 ° C. for 1 hour in an oil bath, and then filtered using a glass filter (G-4), and washed with water. Thereafter, deaeration drying was performed to obtain a powder surface-modified with sodium sulfonate.

Using a packer and a pump, 3 g of the obtained surface-modified powder was packed into a stainless steel column having an inner diameter of 4.6 mm and a length of 25 cm by an equilibrium slurry method to prepare a packed column. This column was connected to high performance liquid chromatography. 2M ammonium acetate-acetic acid (pH 4.6) as mobile phase
Was flowed at a flow rate of 1 ml / min, a standard mixture of uracil, guanine, adenine and cytosine was injected and detected at 254 nm using a UV detector to obtain a chromatogram. As a result,
The retention time and the number of theoretical plates for each peak were as follows.

Example 2 10 kg of cobalt-γ-iron oxide was put into a rotary double cone type reaction vessel (made of stainless steel, equipped with a heat retaining jacket) having a capacity of 100 l. On the other hand, 5 kg of tetramethyltetrahydrogencyclotetrasiloxane was placed in a stock solution supply tank (stainless steel, equipped with a heat retaining jacket) directly connected to the reaction tank with a stainless steel tube. Next, the pressure of the system was reduced to 100 mmHg by a vacuum pump.

The heat medium heated to 90 ° C. was supplied from the heat medium heating tank to the reaction tank and the heat retaining jacket of the stock solution supply tank by a circulation pump to maintain the temperature of the system at 90 ° C. The rotation of the reaction tank is controlled by a timer.
This was performed by rotating three times after standing still for 10 minutes, and the operation of mixing and stirring cobalt-γ-iron oxide in the reaction tank was repeated for 10 hours. Thereafter, nitrogen gas was introduced into the system to return to normal pressure, and 10.3 kg of the treated powder was taken out. The treated powder exhibited significant hydrophobicity without the hydrophilicity seen in untreated cobalt-γ-iron oxide, and the linalool degradability was lost.

Example 2.1 100 g of the silicone polymer-coated cobalt-γ-iron oxide of Example 2 was placed in a 500 ml eggplant-shaped flask.
To this, 10 mg of chloroplatinic acid, 100 ml of allyl glycidyl ether and 100 ml of isopropyl alcohol were added as a catalyst, and the mixture was heated and refluxed at 80 ° C. for 6 hours in an oil bath, and then filtered using a glass filter (G-4).
And then degassed and dried.
γ-iron oxide was obtained.

Example 2.1.1 50 g of the spacer-group-added cobalt-γ-iron oxide obtained in Example 2.1 was placed in a 200 ml eggplant-shaped flask, and 100 ml of aqueous ammonia was added to the flask for 4 hours in an oil bath.
After heating at 0 ° C., the solution was filtered using a glass filter (G-4), washed with water, and then degassed and dried to obtain a powder surface-modified with amino groups.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 2.1.2 50 g of the spacer-group-added cobalt-γ-iron oxide obtained in Example 2.1 was placed in a 200 ml eggplant-shaped flask, and 100 ml of a 0.5 mol / l hydrogen cyanide aqueous solution was added thereto. After heating and refluxing at ℃, the mixture was filtered using a glass filter (G-4) and further 500 ml of acetone.
And dried by degassing to obtain a powder surface-modified with a cyano group.

Example 3 5 kg of titanium dioxide was placed in a vibration type reaction tank (made of stainless steel, with a heat retaining jacket) having a volume of 100 l. The temperature of the reaction tank and the treatment liquid supply tank (stainless steel, equipped with a heat insulation jacket) of 10 liters directly connected to the reaction tank were supplied to each heat insulation jacket from the heat medium heating tank by a circulation pump with a heat medium heated to 90 ° C. To 90 ° C. 500 g of tetramethyltetrahydrogencyclotetrasiloxane was added to the treatment tank, and nitrogen gas was supplied to the treatment liquid supply tank at 2 l / min to bubble the treatment liquid. In addition, a condenser is attached to the reaction tank, and nitrogen gas is released therefrom so that unreacted treating agent can be recovered. The reaction tank was rotated for 1 minute at intervals of 10 minutes, and the operation of mixing titanium dioxide in the reaction tank was repeated for 10 hours, and 5.2 kg of treated powder was taken out. This treated powder showed remarkable hydrophobicity, and the linalool decomposability had disappeared.

Example 3.1 100 g of the silicone polymer-coated titanium dioxide of Example 3 was placed in a 500 ml eggplant-shaped flask, to which 10 mg of chloroplatinic acid and 10 g of allyl glycidyl ether were added as catalysts.
After adding 0 ml and 100 ml of isopropyl alcohol, the mixture was heated and refluxed at 80 ° C. for 6 hours in an oil bath.
The resultant was filtered using -4), further washed with 1000 ml of acetone, and degassed and dried to obtain a spacer group-added titanium dioxide.

Example 3.1.1 50 g of the spacer group-added titanium dioxide obtained in Example 3.1 was placed in a 200 ml eggplant-shaped flask, and
After adding 100 ml of a 1 mol / l sodium sulfite aqueous solution and heating at 80 ° C. for 4 hours in an oil bath, a glass filter (G-4)
After washing with water, deaeration and drying were performed to obtain a powder surface-modified with sodium sulfonate.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 3.1.2 50 g of the spacer-group-added titanium dioxide obtained in Example 3.1 was placed in a 200-ml eggplant-shaped flask, and 100 ml of monoglycerin and 0.1 g of zinc zinc tetrafluoride were added thereto. After heating and refluxing at ° C, the mixture was filtered using a glass filter (G-4), washed with water, degassed and dried to obtain a powder surface-modified with monoglycerin.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 3.1.3 50 g of the spacer-group-added titanium dioxide obtained in Example 3.1 was placed in a 200 ml eggplant-shaped flask, and 100 ml of diglycerin and 0.1 g of zinc zinc tetrafluoride were added thereto. After heating and refluxing at ° C, the mixture was filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with diglycerin.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 3.1.4 Iron oxide, zinc oxide and kaolin were obtained in the same manner as in the surface-modified powder obtained in Example 3.1.3. Using these three kinds of surface-modified powders, calamine lotions shown below were produced.

(1) Glycerin 4.0% (2) Surface-modified iron oxide 0.15% (3) Surface-modified zinc oxide 0.5% (4) Surface-modified kaolin 1.0% (5) Camphor 0.15% (6) Ethanol 14.0% (7) Perfume 8) Purified water 80.2% After dissolving in (1), (6) and (7), add (5) in advance to (8) with (2) to (4) and mix well to wet the powder. Dispersed to give calamine lotion.

Example 3.2 100 g of the silicone polymer-coated titanium dioxide of Example 3 was placed in a 500 ml eggplant-shaped flask, to which 10 mg of tributylamine / chloroplatinate, 50 g of p-vinylaniline, and 100 ml of toluene were added as catalysts.
After heating and refluxing at 110 ° C for a time, a glass filter (G-
4) Filter using, wash with 1000 ml of acetone,
Degassing drying was performed to obtain a spacer group-added titanium dioxide.

Example 3.2.3 50 g of the spacer group-added titanium dioxide obtained in Example 3.2 was dispersed in a solution of 10 ml of concentrated hydrochloric acid and 100 ml of water and cooled to 5 ° C. To this, a solution of 2.0 g of sodium nitrite dissolved in 20 ml of water was added. On the other hand, 200m
l Place 60 ml of 10% sodium hydroxide solution in a beaker,
-3.0 g of naphthol was added and dissolved, and cooled to 5 ° C. When the diazonium salt was added very slowly to the β-naphthol solution cooled to 5 ° C. while stirring, a red powder was obtained. This was filtered using a glass filter (G-4), further washed with 500 ml of water and then with 200 ml of acetone, and degassed and dried to obtain titanium dioxide to which a red pigment was bound.

Example 4 500 g of mica and 100 g of tetramethyltetrahydrogencyclotetrasiloxane were placed in separate containers, and a gas sterilizer Kapocalizer CL-30B (Fuji Electric C
o. Ltd.), the inner pressure was reduced to 100 mmHg by an aspirator, and the temperature was maintained at 30 ° C.

Six hours later, air was introduced and the pressure was returned to normal pressure, and the air was evacuated several times to obtain 545 g of treated powder. This treated powder had lost the linalool degradability, which indicates remarkable hydrophobicity.

Example 4.1 Silicone polymer coated mica 100 of Example 4
g in a 500 ml eggplant-shaped flask, to which 10 mg of chloroplatinic acid, 100 ml of allyl glycidyl ether and 100 ml of isopropyl alcohol were added as a catalyst, and the mixture was placed in an oil bath for 6 hours.
After heating under reflux at 0 ° C., the solution was filtered using a glass filter (G-4), further washed with 1000 ml of acetone, and degassed and dried to obtain a mica having a spacer group added thereto.

Example 4.1.1 50 g of the spacer group-added mica obtained in Example 4.1 was placed in a 200 ml eggplant-shaped flask, and 100 ml of monoglycerin and 0.1 g of zinc zinc tetrafluoride were added thereto, and the mixture was placed in an oil bath at 100 ° C. for 4 hours. After heating and refluxing, filtration using a glass filter (G-4), washing with water, and deaeration drying were performed to obtain a powder surface-modified with monoglycerin.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 4.1.2 50 g of the spacer group-added mica obtained in Example 4.1 was placed in a 200 ml eggplant-shaped flask, and 100 ml of diglycerin and 0.1 g of zinc zinc tetrafluoride were added thereto, and the mixture was placed in an oil bath at 100 ° C. for 4 hours. After heating and refluxing, a filter was used with a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with diglycerin.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 5 10 kg of mica titanium was placed in a rotary double-cone type reaction tank having a capacity of 100 l (made of stainless steel and equipped with a heat retaining jacket). The reaction tank, and a processing liquid supply tank (stainless steel,
The temperature of the heating medium (with a heat retaining jacket) is set to 90 ° C. by supplying the heat medium heated to 90 ° C. from the heat medium heating tank to each heat retaining jacket by a circulation pump. 5 kg of tetramethyltetrahydrogencyclotetrasiloxane was added to the treatment tank, and nitrogen gas was supplied to the treatment liquid supply tank at 2 l / min to bubble the treatment liquid. In addition, a condenser is attached to the reaction tank, and nitrogen gas is released therefrom so that unreacted treating agent can be recovered. Further, the reaction tank was rotated for 1 minute at intervals of 10 minutes, and the operation of mixing mica titanium in the reaction tank was repeated for 10 hours, thereby taking out 10.2 kg of the treated powder. This treated powder showed remarkable hydrophobicity, and the linalool decomposability had disappeared.

Example 5.1 100 g of the silicone polymer-coated titanium mica of Example 5 was placed in a 500 ml eggplant-shaped flask, and 10 mg of chloroplatinic acid and 100 m of allyl glycidyl ether were added as a catalyst.
and 100 ml of isopropyl alcohol, and the mixture was heated and refluxed at 80 ° C. for 6 hours in an oil bath.
4) Filter using, wash with 1000 ml of acetone,
Deaeration and drying were performed to obtain a spacer group-added titanium mica.

Example 5.1.1 50 g of the spacer group-added mica titanium obtained in Example 5.1 was placed in a 200 ml eggplant-shaped flask, to which 150 ml of monoglycerin and 0.1 g of zinc zinc tetrafluoride were added, and the mixture was placed in an oil bath for 4 hours. After heating and refluxing at ° C, the mixture was filtered using a glass filter (G-4), washed with water, degassed and dried to obtain a powder surface-modified with monoglycerin.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 5.1.2 50 g of the spacer group-added mica titanium obtained in Example 5.1 was placed in a 200 ml eggplant-shaped flask, and 100 ml of diglycerin and 0.1 g of zinc zinc tetrafluoride were added thereto. After heating and refluxing at ° C, the mixture was filtered using a glass filter (G-4), washed with water, deaerated and dried to obtain a powder surface-modified with diglycerin.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 6 500 g of carbon and 100 g of tetramethyltetrahydrogencyclotetrasiloxane were put in separate containers, and a gas sterilizer Capocalizer CL-30B (Fuji Electr
ic Co. Ltd.), the inner pressure was reduced to 100 mmHg by an aspirator, and the temperature was maintained at 30 ° C.

Six hours later, air was returned to normal pressure by introducing air, and then exhausted several times to obtain 555 g of treated powder. This treated powder showed remarkable hydrophobicity and the linalool decomposability had disappeared.

Example 6.1 100 g of this silicone polymer coated carbon
Was placed in a 500 ml eggplant-shaped flask, to which 10 mg of chloroplatinic acid, 100 ml of allyl glycidyl ether and 100 ml of isopropyl alcohol were added as a catalyst, and the mixture was placed in an oil bath for 6 hours.
After heating under reflux at 0 ° C., the solution was filtered using a glass filter (G-4), further washed with 1,000 ml of acetone, and degassed and dried to obtain spacer group-added carbon.

Example 6.1.1 50 g of the spacer group-added carbon obtained in Example 6.1 was placed in a 200 ml eggplant-shaped flask, to which 100 g of monoglycerin and 0.1 g of zinc zinc tetrafluoride were added, and the mixture was placed in an oil bath at 100 ° C. for 4 hours. After heating and refluxing, filtration using a glass filter (G-4), washing with water, and deaeration drying were performed to obtain a powder surface-modified with monoglycerin.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 6.1.2 50 g of the spacer group-added carbon obtained in Example 6.1 was placed in a 200-ml eggplant-shaped flask, and 100 ml of diglycerin and 0.1 g of zinc zinc tetrafluoride were added thereto, and the mixture was placed in an oil bath at 100 ° C. for 4 hours. After heating under reflux, the mixture was filtered using a glass filter (G-4), washed with water, degassed and dried to obtain a powder surface-modified with diglycerin.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 7 200 g of Blue No. 404 was dispersed in 800 ml of dichloromethane, and hydrogen methyl polysiloxane (molecular weight: about 30
00) 6 g was added, and the mixture was heated under reflux at 50 ° C. for 2 hours, and then dichloromethane was distilled off at 100 ° C.

Example 7.1 Silicone polymer coated blue 404 of Example 7
No. 200 g was placed in a 500 ml eggplant-shaped flask, and as a catalyst, 10 mg of chloroplatinic acid and 100 ml of allyl glycidyl ether were used.
And 100 ml of isopropyl alcohol, and heated and refluxed at 80 ° C. for 6 hours in an oil bath.
4) Filter using, wash with 1000 ml of acetone,
After degassing and drying, Blue No. 404 with a spacer group added was obtained.

Example 7.1.1 50 g of the spacer group-added blue color No. 405 obtained in Example 7.1 was placed in a 200 ml eggplant-shaped flask, and 100 ml of diglycerin and 0.1 g of zinc zinc tetrafluoride were added thereto, followed by 4 hours in an oil bath. After heating and refluxing at 100 ° C., the solution was filtered using a glass filter (G-4), and ethanol 50
After washing with 0 ml and deaeration drying, a surface-modified powder was obtained.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 8 200 g of yellow iron oxide was put in a planetary ball mill, mixed and ground for 5 minutes, and then hydrogen methyl polysiloxane (molecular weight)
6000) and further mixed and ground for 3 hours.

Example 8.1 200 g of the yellow iron oxide coated with the silicone polymer of Example 8 was placed in a 500 ml eggplant-shaped flask, and 10 mg of chloroplatinic acid and 100 m of allyl glycidyl ether were added thereto as a catalyst.
and 100 ml of isopropyl alcohol, and the mixture was heated and refluxed at 80 ° C. for 6 hours in an oil bath.
4) Filter using, wash with 1000 ml of acetone,
Deaeration drying was performed to obtain a yellow iron oxide having a spacer group added thereto.

Example 8.1.1 50 g of the spacer group-added yellow iron oxide obtained in Example 8.1 was placed in a 200 ml eggplant-shaped flask, and 1 m
ol / l sodium sulfite aqueous solution (100 ml)
After heating at 80 ° C for a time, the mixture was filtered using a glass filter (G-4), further washed with 500 ml of acetone, and degassed and dried to obtain a surface-modified powder.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 9 100 g of metal iron powder and 50 g of tetrahydrotetramethylcyclotetrasiloxane were placed in separate containers and left at 80 ° C. in a desiccator. After 72 hours, the metal iron was taken out and the weight was measured.106 g of treated yellow iron oxide was obtained,
When left in a dryer at 50 ° C. for 24 hours, 103 g of treated metal iron was obtained.

Example 9.1 100 g of the silicone polymer-coated metal iron of Example 9 was placed in a 500 ml eggplant-shaped flask, and 10 mg of chloroplatinic acid and 100 ml of allyl glycidyl ether were added thereto as a catalyst.
And 100 ml of isopropyl alcohol, and heated and refluxed at 80 ° C. for 6 hours in an oil bath.
4) Filter using, wash with 1000 ml of acetone,
Degassing and drying were performed to obtain a metal iron with a spacer group added.

Example 9.1.1 50 g of the spacer-group-added metal iron obtained in Example 9.1 was placed in a 200 ml eggplant-shaped flask, 100 ml of aqueous ammonia was added thereto, and the mixture was heated at 80 ° C. for 4 hours in an oil bath. The solution was filtered using (G-4), further washed with 500 ml of acetone, and degassed and dried to obtain a surface-modified powder.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 9.2 100 g of the silicone polymer-coated metal iron of Example 9 was placed in a 500 ml eggplant-shaped flask, to which 10 mg of chloroplatinic acid, 100 ml of 3-chloropropyldimethylvinylsilane and 100 ml of isopropyl alcohol were added as catalysts, and the mixture was placed in an oil bath. After heating and refluxing at 80 ° C. for a time, the mixture was filtered using a glass filter (G-4), and acetone 1000 was further added.
After washing with ml, degassing and drying were performed to obtain metal iron with a spacer group added.

Example 9.2.1 50 g of the spacer-group-added metal iron obtained in Example 9.2 was placed in a 200 ml eggplant-shaped flask, and 1 mol thereof was added thereto.
100 l / l sodium sulfite was added and the mixture was heated under reflux at 100 ° C for 5 hours, filtered using a glass filter (G-4), further washed with 500 ml of water and then with 500 ml of acetone, deaerated and dried with sodium sulfonate. A surface-modified powder was obtained.

The obtained surface-modified powder showed remarkable hydrophilicity.

Example 10 10 g of a monolithic carrier of cordierite (2MgO.2Al ₂ O ₃ .5SiO ₂ ) ceramic and 10 g of tetramethylcyclotetrasiloxane were placed in a gesicator and left at 60 ° C. for 3 days. Thereafter, the monolith carrier was taken out and dried at 80 ° C. for 6 hours to obtain 10.2 g of a treated monolith carrier.

Example 10.1.10 g of the silicone polymer-coated monolithic carrier of Example 10
Was placed in a 500 ml eggplant-shaped flask, 10 mg of chloroplatinic acid, 10 ml of allyl alcohol and 100 ml of isopropyl alcohol were added thereto as a catalyst, and the mixture was heated and refluxed at 80 ° C. for 4 hours in an oil bath, and then the glass filter (G-4) was removed. The mixture was filtered, washed with acetone, and degassed and dried to obtain a spacer group-added silica gel.

Example 10.1.1 10 g of the spacer group-added monolith carrier obtained in Example 10.1 was placed in a 200 ml eggplant-shaped flask, and 50 ml of a 1.5 mol / l aqueous sodium periodate solution (pH 8.5) was added thereto.
Then, 0.3 g of potassium permanganate was added, and the mixture was heated at 100 ° C. for 2 hours in an oil bath, washed with acetone, degassed and dried to obtain a monolith carrier surface-modified with a carboxyl group.

Example 10.1.1.1 10 g of the monolithic carrier surface-modified with a carboxyl group obtained in Example 10.1.1 was added to 200 ml of a 1% by weight anti-hepatitis B human immunoglobulin phosphate buffer (1/10 M, pH 8.0). Dipped. Thereafter, N-hydroxy-5-norbornel-2,3-
500 mg of dicarboximide was added, and the reaction was carried out for 24 hours, followed by thorough washing with physiological saline. Thus, an anti-hepatitis B antibody-immobilized monolithic carrier was obtained.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code Agency reference number FI Technical indication location B01J 20/32 B01J 20/32 Z C09C 3/12 C09C 3/12 C12N 11/08 C12N 11/08 Z G01N 30/48 G01N 30/48 L (72) Inventor Mikiyoshi Nakano 1050 Nippa-cho, Kohoku-ku, Yokohama Inside Shiseido Research Laboratories Co., Ltd. In-house (72) Inventor Kota Nakata 1050 Nippa-cho, Kohoku-ku, Yokohama-shi Inside Shiseido R & D Co., Ltd. JP-A-133458 (JP, A) JP-A-53-81295 (JP, A) JP-A-46-1837 (JP, A) JP-B-55-49259 (JP, B2)

Claims (1)

(57) [Claims] (A) a weight-average molecular weight containing at least one reactive moiety which is a Si-H moiety or a derivative thereof;
Preparing a solid material having at least 200,000 silicone polymer coatings on its surface; (b) at least one Si-bonding moiety capable of reacting with the reactive moiety and bonding to the Si atom, and a chemically modified receptor Treating the solid material of step (a) with a spacer compound having at least one moiety to cause the reactive moiety and the Si-bonded moiety to react in a solid-liquid reaction to bind the spacer compound to the silicone polymer film And (c) a modified solid material carrying a silicone polymer film having a functional part on the surface, wherein the functional part is introduced by chemically modifying the chemical modification accepting part.