JP6964017B2 - Manufacturing method of core-shell type silica - Google Patents

Description

The present invention relates to a method for producing core-shell type silica.

Spherical silica is used as a filler for liquid chromatography, a carrier for an immobilized enzyme, a shape-selective catalyst, a material for adsorbing / separating various ions, a matte material for paints, a raw material for cosmetics, and the like.
The form of spherical silica includes solid silica, hollow silica, porous silica, core-shell type silica and the like. Of these, core-shell type silica is obtained by forming a shell layer made of porous silica on the surface of silica core particles made of solid silica.

When porous silica is used as a filler for liquid chromatography, the porous silica is required to have low liquid feeding resistance and high separation efficiency.
In order to reduce the liquid feeding resistance, the particle size of the porous silica may be increased. However, when the particle size of the porous silica is increased, it takes time for the substance to be separated, which is adsorbed by the porous silica and reaches the central portion of the porous silica, to be released from the porous silica, so that the separation efficiency is improved. It gets lower. On the other hand, if the particle size of the porous silica is reduced in order to increase the separation efficiency, the liquid feeding resistance increases.

In order to achieve both low liquid feed resistance (pressure loss suppression) and high separation efficiency, the use of core-shell silica can be considered. Since the core-shell type silica has non-porous silica core particles in the center, the substance to be separated adsorbed on the core-shell type silica stays in the shell layer near the surface. Therefore, the time from when the substance to be separated is adsorbed on the core-shell type silica to when it is released is short, and the separation efficiency is high. Further, if the silica core particles in the central portion are increased, the particle size of the core-shell type silica can be increased while suppressing the thickness of the shell, so that the liquid feeding resistance can be reduced without lowering the separation efficiency.

In Patent Document 1, a silica raw material is added to and reacted with a dispersion liquid in which substantially non-porous silica core particles are dispersed in a dispersion medium containing a surfactant, and silica and a surfactant are applied to the surface of the silica core particles. A method for producing a core-shell type silica has been proposed, which forms a shell precursor containing the mixture and removes a surfactant from the shell precursor to form a porous shell.
In Patent Document 1, a surfactant such as dodecylamine is used to adsorb a silica raw material such as tetraethoxysilane to the silica core particles for reaction, but it is difficult to form a thick shell layer.

Further, Patent Documents 2 and 3 propose a method for producing core-shell type silica by adsorbing silica sol on silica core particles via an organic substance, removing the organic substance by firing or the like to form a porous shell layer. Has been done.
In Patent Document 2, charged silica nanoparticles are attached to spherical silica in a solvent containing a polymer electrolyte such as poly (diallyldimethylammonium) chloride.
In Patent Document 3, silica sol seed particles are grown into 1.90 μm core particles, and the core particles are treated with an organic substance such as poly (urea-formaldehyde) or poly (melamine), and then treated with a 2 nm sol solution to form a core. A silica sol is attached to the particles.

International Publication No. 2007/122930 U.S. Patent Application Publication No. 2009/0297853 U.S. Pat. No. 8,864,988 Special Fair 4-41305 Gazette

In the conventional method for producing core-shell type silica, an anionic silica sol is electrostatically applied to a non-porous silica core on which a cationic polymer is electrostatically adsorbed, and then the cationic polymer is removed by firing. A porous shell layer is fixed to the surface of the silica core.
In the methods of Patent Documents 2 and 3, since the thickness of one shell layer is insufficient, a plurality of shell layers are laminated in order to obtain a desired thickness of the porous shell layer. As the number of times the shell layer is laminated increases, there is a problem that the number of steps increases.
Further, depending on the surface layer action of the cationic polymer, a gap may be formed between a plurality of shell layers, which causes a problem of causing a decrease in the theoretical plate number of chromatography.

On the other hand, Patent Document 4 proposes a method of immobilizing porris succinimides on a substrate material via an amine functional group as a carrier material for chromatography. Thereby, the succinimide unit can be hydrolyzed to prepare a cation exchange substance for protein. However, there is no example of applying this to core-shell type silica.

An object of the present invention is to increase the thickness of one layer of the porous shell layer in the core-shell type silica to reduce the number of layers of the entire shell layer.

The gist of the present invention is as follows.
(1) A polymer compound having a succinimide skeleton is reacted on the surface of silica particles, a polyamine compound is reacted to obtain modified silica modified with a cationic polymer compound, and a silica raw material is attached to the modified silica. A method for producing core-shell type silica, which removes a cationic polymer compound to obtain a silica-shell layer.
(2) The method for producing core-shell type silica according to (1), wherein the silica particles are solid silica.
(3) The method for producing core-shell silica according to (1) or (2), wherein the surface of the silica particles is reacted with an amine compound and then a polymer compound having a succinimide skeleton is reacted.
(4) The method for producing core-shell type silica according to (3), ^{wherein the amine compound is reacted so as to be 0.05 to 4 μmol / m 2} per surface area of the silica particles.
(5) The method for producing core-shell type silica according to any one of (1) to (4), wherein the polymer compound having a succinimide skeleton is reacted with 1 part by mass of the silica particles in an amount of 10 parts by mass or less.
(6) The method for producing core-shell silica according to any one of (1) to (5), wherein the polymer compound having a succinimide skeleton has a weight average molecular weight of 5,000 to 500,000.
(7) The method for producing core-shell silica according to any one of (1) to (6), wherein the polyamine compound is an aliphatic diamine compound.
(8) The core-shell type silica according to any one of (1) to (7), wherein the modified silica and the silica raw material are adjusted to pH 1 to pH 10 in a solvent to attach the silica raw material to the modified silica. Manufacturing method.
(9) A core-shell type silica is obtained by the production method according to any one of (1) to (8), a polymer compound having a succinimide skeleton is reacted on the surface of the core-shell type silica, and a polyamine compound is reacted. A core shell having a plurality of shell layers, which obtains modified silica modified with a cationic polymer compound, attaches a silica raw material to the modified silica, removes the cationic polymer compound, and obtains an outermost silica shell layer. Method for manufacturing type silica.

According to the present invention, in the core-shell type silica, the thickness of one layer of the porous shell layer can be increased to reduce the number of layers of the entire shell layer.

FIG. 1 is a cross-sectional photograph of the core-shell type silica of Example 67. FIG. 2 is a cross-sectional photograph of the core-shell type silica of Example 68, in which (a) is 25,000 times and (b) is 100,000 times. FIG. 3 is a cross-sectional photograph of the core-shell type silica of the reference example. FIG. 4 is an overall photograph of the core-shell type silica of (a) Example 68 and (b) Reference Example. FIG. 5 is a graph showing the pore distribution of the pore physical characteristics of Examples 67, 68, 74, and Reference Example. FIG. 6 is a van Deemter plot of core-shell silica of Example 67, Example 68, Example 74, and Reference Example.

Hereinafter, the present invention will be described, but the present invention is not limited by the examples in the following description.

In the method for producing core-shell type silica according to the present invention, a polymer compound having a succinimide skeleton is reacted on the surface of silica particles, and a polyamine compound is reacted to obtain modified silica modified with a cationic polymer compound. It is characterized in that a silica raw material is attached to modified silica to remove a cationic polymer compound to obtain a silica shell layer.
According to the present invention, in the core-shell type silica, the thickness of one layer of the porous shell layer can be increased to reduce the number of layers of the entire shell layer.
In the following description, the polymer compound having a succinimide skeleton is also referred to as "poriscinimides", and the modified silica modified with the cationic polymer compound is also referred to as "modified silica".
The silica particles on which the silica shell layer is formed are not particularly limited, but solid silica or solid silica on which at least one silica shell layer is formed is used. In the following description, solid silica is also referred to simply as "silica core".

According to the present invention, porris succinimides are reacted on the surface of silica particles, and a polyamine compound is reacted with the porris succinimides to open the imide ring of the porisuccinimides, introduce an amino group, and modify the surface with a cationic polymer compound. The resulting silica is obtained. Cationic polymer compounds derived from succinimides have a good rise from the surface of silica particles. By adhering the silica raw material to this cationic polymer compound, the thickness of the porous shell layer formed by the silica raw material can be increased.
The porris succinimides are reacted on the surface of the silica particles by reacting an amine compound on the surface of the silica particles to introduce an amino group and reacting the amino group with the porris succinimides. As a result, the silica shell layer can be made thicker and the layer thickness can be made uniform.
According to the present invention, since the thickness of one shell layer can be increased, the number of times the shell layers are laminated can be reduced in order to obtain a shell layer having a desired thickness.

As an example of the present invention, a step of introducing an amino group (aminopropyl group) onto the surface of silica particles, reacting the amino group with succinimide, and further reacting with ethylenediamine to obtain modified silica is shown below.

In the present invention, in order to introduce the porris succinimides on the surface of the silica particles, it is preferable to react the porris succinimides on the surface of the silica particles after reacting the amine compound.

In the present invention, it is preferable to use solid silica as the silica particles for forming the first layer shell. The solid silica core serves as the central portion of the core-shell type silica, and is not particularly limited, but preferably has the following physical properties.
The solid (substantially non-porous) silica core is preferably dense enough that the sample substance does not penetrate inside when used in liquid chromatography applications.
For example, in a silica core, the specific surface area of the silica core measured by the constant volume gas adsorption method ^{is preferably 6 m 2} / g or less. As a result, when the core-shell type silica is used as a filler for liquid chromatography, the substance to be separated adsorbed on the shell layer is not adsorbed on the silica core, and the separation efficiency can be improved.

The average particle size of the silica core is preferably 0.1 to 100 μm, more preferably 0.1 to 50 μm, and even more preferably 0.1 to 10 μm. By setting the average particle size of the silica core to 0.1 μm or more, a core-shell type silica having a large particle size can be obtained. By setting the average particle size of the silica core to 100 μm or less, a porous shell layer that is substantially effective for separation can be formed on the silica core.
Further, in the silica core, the ratio (D90 / D10) of the particle size (D10) of 10% and the particle size (D90) of 90% is 1 in the Coulter counter method from the smallest integrated amount of the particle size distribution on the volume basis. It is preferably 0.8 or less, more preferably 1.7 or less, and even more preferably 1.6 or less. The closer D90 / D10 is to 1, the more uniform the particle size is, which is preferable.
The pore volume of the silica core is preferably 0 mL / g or more and less than 0.01 mL / g.

As the shape of the silica core, spherical particles are preferable, and spherical particles including a true sphere and an ellipsoid can be used. In the use of the chromatography carrier, a shape close to a true sphere is preferable from the viewpoint of packing property to the column and suppression of pressure loss during use. The sphericity of the silica core may be, for example, 0.8 or more, preferably 0.9 or more. The method for measuring the physical property value of the silica core is as described in the core-shell type silica described later.

As commercially available products of the silica core, for example, "High Presica FQ-N2N", "High Presica SS-N3N", "High Presica TS-N3N", "High Presica FR-N2N" manufactured by Ube Exsymo can be used. These can be used alone or in combination of two or more.

The amino group introduced by reacting the surface of the silica particles with the amine compound may be a primary amino group, a secondary amino group, or a combination thereof.
As the amine compound, it is preferable to use an amine compound having a silyl group together with an amino group because the silyl group is adsorbed on the surface of the silica particles and the amino group is easily introduced.
Examples of the silyl group include a monoalkylsilyl group, a dialkylsilyl group, and a trialkylsilyl group; a monoalkoxysilyl group, a dialkoxysilyl group, and a trialkoxysilyl group. As the alkyl group and the alkoxy group of the silyl group, for example, the number of carbon atoms is preferably 1 to 6, and more preferably 1 to 3.

As the amine compound having a silyl group together with an amino group, for example, a compound represented by the following general formula (1) can be used.

In the general formula (1), R ¹ , R ² , and R ³ are independently alkyl groups having 1 to 6 carbon atoms, more preferably 1 to 3 carbon atoms, and 1 to 6 carbon atoms, more preferably 1 to 3 carbon atoms, respectively. Is an alkoxy group, a hydroxy group, or a hydrogen atom, and ^{at least one of R 1} , R ² , and R ³ is preferably an alkoxy group. Further, R ⁴ is an arbitrary group having a single bond or a divalent value, preferably an alkylene group having 1 to 6 carbon atoms, and more preferably a propylene group. Further, R ⁵ and R ⁶ are independently hydrogen atoms or alkyl groups having 1 to 6 carbon atoms, ^{and both R 5} and R ⁶ are preferably hydrogen atoms.

Specific examples of the amine compound having a silyl group together with an amino group include 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-aminopropyldiethoxymethylsilane, 3-aminopropylethoxydimethylsilane, and the like. Examples include N-methyl-3-aminopropyltrimethoxylane, N- (2-aminoethyl) -3-aminopropyltrimethoxysilane, 3- (trimethoxysilylpropyl) diethylenetriamine, and bis (3-methoxysilylpropyl) amine. Be done.

As one method of reacting the amine compound with the surface of the silica particles, the silica particles can be added to a solvent to prepare a slurry, and the amine compound can be added to the slurry and reacted to introduce an amino group onto the surface of the silica particles. ..
As the solvent of the slurry, an organic solvent such as toluene, xylene, methanol, ethanol and isopropyl alcohol can be used. The silica particle concentration in the slurry can be 1 to 40% by mass. Further, the amine compound may be added to the slurry in the state of a solution dissolved in an organic solvent.
If necessary, it can be heated to 40 to 150 ° C. and reacted over 0.5 to 48 hours.
After the reaction, if necessary, silica having an amino group introduced may be washed with an organic solvent. For example, toluene, acetone, and hexane can be washed in this order. Excess amine compounds can be removed by washing.

The amine compound is preferably reacted so as to be ^{0.05 to 4 μmol / m 2} per surface area of the silica particles.
When this value is 0.05 μmol / m ² or more, the surface of the silica particles can be uniformly coated with the amine compound. This value is more preferably 0.2 μmol / m ² or more, and even more preferably 1.3 μmol / m ² or more.
On the other hand, when this value is 4 μmol / m ² or less, the surface of the silica particles can be smoothly coated with the amino group-containing compound, and a more appropriate amount of porris succinimide can be supported. This value is more preferably 2.7 μmol / m ² or less, and even more preferably 2.2 μmol / m ² or less.

The amount of the amine compound per surface area of the silica particles can be obtained from the input amount and surface area of the silica particles and the input amount of the amine compound under the condition that the entire input amount of the amine compound reacts with the silica particles.

In the present invention, poriscinimides are polymer compounds having repeating units of a succinimide skeleton having an imide ring structure.
When the amino group introduced into the surface of the silica particles reacts with the porriscinimides, a part of the succinimide skeleton opens at the carbonyl group portion to form an amide bond "-NH-CO-" with the amino group, and the silica particles Porisuccinimides are introduced onto the surface via an amide bond.

The weight average molecular weight (Mw) of the porris succinimides is preferably 5,000 or more, more preferably 80,000 or more, and further preferably 100,000 or more. As a result, the thickness of the shell layer per layer can be increased.
On the other hand, the weight average molecular weight (Mw) of the porris succinimides is preferably 500,000 or less, more preferably 300,000 or less, and further preferably 200,000 or less. As a result, the porris succinimides have an appropriate solubility and can be efficiently introduced into the surface of the silica particles.

In the present invention, as the polymer compound having a succinimide skeleton, a succinimide, a succinimide derivative, a copolymer of a succinimide monomer and another polymerizable monomer, or the like can be used alone or in combination of two or more.
In the present invention, porris succinimides may be synthesized and prepared. Hereinafter, an example of a method for synthesizing porris succinimides will be described.
Poris succinimides are obtained by polymerizing aspartic acids such as D, L-aspartic acid, D-aspartic acid, and L-aspartic acid. The polymerization is a solid reaction and can be carried out at a heating temperature of 80 to 250 ° C. for 1 to 100 hours. Further, it may be polymerized by solution polymerization using a polymerization solvent such as isopropyl alcohol (IPA), sulfolane, N, N-dimethylformamide (DMF).
If necessary, the product may be washed as a water slurry, for example, water and acetone in that order. Excess raw material can be removed by washing.

As a method for obtaining higher molecular weight porris succinimides, for example, an acid may be added to the aspartic acids, mixed and heated. As the acid, phosphoric acid, phosphorus pentoxide, polyphosphoric acid, sulfuric acid, sulfite, alkylsulfonic acid, arylsulfonic acid, chloric acid, chloric acid and hypochlorous acid can be used, and phosphoric acid is preferable.
If necessary, the product may be washed as a water slurry, for example, water and acetone in that order. Phosphoric acid can be removed along with excess raw material by washing.

The amount of acid used (molar ratio) to aspartic acid is preferably 0.01 or more, more preferably 0.1 or more, and further preferably 0.1 or more. Is 0.3 or more. This makes it possible to increase the molecular weight of porris succinimides.
On the other hand, this "amount of acid used (mol) / amount of aspartic acid used (mol)" is preferably 0.5 or less, more preferably 0.4 or less. This makes it possible to prevent the product porris succinimides from being dissolved in an acid and polymerized, and then fused and solidified.

The porris succinimides produced by polymerization or the like including the above method are in the state of a mixture of low molecular weight to high molecular weight porris succinimides.
As one method for obtaining high molecular weight poriscinimides from such a mixed state, for example, a mixture containing low molecular weight to high molecular weight poriscinimides is prepared in DMF, N-methyl-2-pyrrolidone (NMP), N, N. '-Dimethylimidazolidinone (DMI), dimethyl sulfoxide (DMSO), sulfolane, dimethyl sulfone, etc. are dissolved, and acetone, methanol, diethyl ether, water, etc. are gradually added to this solution to form a high molecular weight poriscinimide. It is obtained by reprecipitating only the species. If necessary, the solution is centrifuged at about 100 to 5,000 rpm to remove the supernatant, so that the yield can be further increased and high molecular weight porris succinimides can be obtained. If necessary, the product may be washed with acetone or the like.

As a method for reacting succinimides with the amino group introduced on the surface of the silica particles, for example, succinimides are converted into DMF, N, N-dimethylacetamide (DMAc), NMP, DMI, DMSO, sulfolane, dimethyl. There is a method in which a succinimide solution is prepared by adding to sulfone or the like, and silica particles having an amino group introduced therein are added to the succinimide solution.
At this time, the concentration of succinimides in the succinimide solution is preferably 0.1 to 30% by mass.
After adding the silica particles into which the amino group has been introduced to the porris succinimide solution, it is preferable to stir at room temperature for 0.5 to 48 hours.
After the reaction, the solution is filtered to obtain silica into which porris succinimides have been introduced. If necessary, the product may be washed with DMF, NMP, DMI, DMSO, sulfolane, dimethyl sulfone and the like, and then washed with acetone, methanol, diethyl ether and water. This is dried to obtain modified silica obtained by reacting the surface of silica particles with porris succinimides in a powder state.

When reacting succinimides, for example, it is preferable to react succinimides at 0.01 to 10 parts by mass with respect to 1 part by mass of silica particles. This value is preferably 2 parts by mass or less, and more preferably 1 part by mass or less. In particular, this value is preferably 0.8 parts by mass or less, more preferably 0.6 parts by mass or less, and may be 0.5 parts by mass or less.

Further, the porris succinimides (molar portion) "{poris succinimides (mol) / amino group (mol) introduced into the silica particles} x 100" with respect to 100 mol parts of the amino group introduced into the silica particles is, for example, 0. It may be in the range of 1 to 1,000 mol parts, preferably 0.5 to 900 mol parts, and more preferably 1 to 400 mol parts.

The molar portion of the porris succinimide with respect to the amino group introduced into the silica particles is the amount of the porris succinimide input and the silica particles under the condition that the entire input amount of the porris succinimide reacts with the amino group introduced into the silica particles. It is obtained from the input amount of the amino group introduced into, that is, the amine compound. When the amine compound contains a plurality of amino groups, the total amount of the plurality of amino groups is calculated.

In the present invention, a compound having two or more amino groups can be used as the polyamine compound, and the amino group may be a primary amino group, a secondary amino group, or a combination thereof.

Examples of the polyamine compound include diamines such as ethylenediamine, 1,3-propylenediamine, 1,4-butylenediamine, and 1,5-amylenediamine;
Triamines such as diethylenetriamine, dipropylenetriamine, 3- (aminopropyl) -ethylenediamine;
Amine compounds having 4 or more amino groups such as triethylenetetramine, N, N, N-tris (2-aminoethyl) amine, polyethyleneimine and the like;
4- (2-Aminoethyl) Pyridine, 3- (2-Aminoethyl) Pyridine, 4- (Aminomethyl) Pyridine, 3- (Aminomethyl) Pyridine, 2- (2-Aminoethyl) Pyrimidine, 4- (2) -Aminoethyl) pyrimidines, 5- (2-aminoethyl) pyrimidines, 2- (aminomethyl) pyrimidines, 4- (aminomethyl) pyrimidines, 5- (aminomethyl) pyrimidines, 2- (3-aminopropyl) imidazoles, Examples thereof include compounds having a nitrogen-containing heterocycle such as 2- (aminomethyl) imidazole.
These may be used alone or in combination of two or more.

Of these, aliphatic polyamines are preferable, and aliphatic diamine compounds are particularly preferable. As such an aliphatic polyamine compound, an aliphatic diamine compound having a carbon chain having 1 to 5 carbon atoms between the amino groups is preferable, and for example, ethylenediamine, 1,3-propylenediamine, 1, 4-Butylenediamine, 1,5-amylenediamine and the like can be preferably used.
As a result, the succinimide skeleton of some or all of the succinimides introduced on the surface of the silica particles via an amide bond is opened, and the carbonyl group of the succinimide skeleton is reacted with one amino group of the polyamine compound to cause poly. The other amino group can be introduced from the carbonyl group of the succinimide skeleton via the carbon chain. In this way, a chain composed of a relatively long organic component can be formed from the surface of the silica particles.

As one method for obtaining the modified silica, for example, the poriscinimide-modified silica obtained in (2) above is used in DMF, DMAc, NMP, DMI, DMSO, dimethyl sulfone, sulfolane, toluene, 1,4-dioxane, tetrahydrofuran and the like. There is a method of making a slurry, adding a polyamine compound to this slurry, and stirring and reacting at room temperature for 0.25 to 48 hours. The slurry before adding the polyamine compound preferably has a concentration of porris succinimide-modified silica of 5 to 60% by mass. If necessary, the product may be washed with DMF, NMP, DMI, DMSO, sulfolane, dimethyl sulfone or the like, and then washed with acetone, methanol, diethyl ether, water or the like.
As a result, cationic polymer compound modified silica is obtained.

It is preferable that the amount of the polyamine compound used is the same as that of the unopened succinimide skeleton among the poriscinimides introduced into the silica particles, and all the unopened succinimide skeletons are opened. Further, the polyamine compound may be excessively blended, and the unreacted polyamine compound may be removed by washing.

In the present invention, the silica raw material is a substance capable of forming silicon dioxide by a treatment such as firing, and silica fine particles, a silica precursor, or a combination thereof can be used.

The average particle size of the silica fine particles is preferably 1 to 100 nm. The silica fine particles may be solid or hollow, and are preferably spherical.
When the average particle size of the silica fine particles is 1 nm or more, more preferably 4 nm or more, a shell layer having a desired pore distribution can be formed.
On the other hand, when the average particle size of the silica fine particles is 100 nm or less, more preferably 40 nm or less, still more preferably 30 nm or less, a shell layer having a uniform thickness, shape, and appearance can be formed.
The pore size of the shell layer of the obtained core-shell type silica can be controlled by the average particle size of the silica fine particles. For example, by using silica fine particles having an average particle diameter of about 17 nm, the pore diameter of the core-shell type silica can be made about 9 to 12 nm.

Colloidal silica can be preferably used as the silica fine particles.
Colloidal silica is provided as a silica sol in which silica fine particles are dispersed in water or an organic solvent such as methanol or ethanol.

As the silica precursor, for example, silicic acid, silicate, silicate alkoxide, or a combination thereof can be used. These silica precursors may be partially hydrolyzed condensates.
As the silicate, alkali metal silicates such as sodium silicate and potassium silicate, alkaline earth metal silicates such as calcium silicate and magnesium silicate can be used.
Examples of the silicate alkoxide include compounds in which 1 to 4 alkoxy groups are introduced into a silicon atom. For example, tetraethoxysilane, tetramethoxysilane, tetraisopropoxysilane, methyltriethoxysilane and the like can be used.

As one method of adhering the silica raw material to the modified silica, for example, there is a method of electrostatically adsorbing the silica raw material to the modified silica by adding the aqueous solution containing the silica raw material to the aqueous solution containing the modified silica.
The aqueous solution containing the modified silica preferably contains, for example, the modified silica at a concentration of 0.01 to 30% by mass.

For the aqueous solution containing the silica raw material, for example, the concentration of the silica raw material is preferably 0.01 to 30% by mass. Here, when colloidal silica is used as the silica raw material, the concentration of the silica raw material is converted by the amount of silica solids in the colloidal silica.
When mixing an aqueous solution containing modified silica and an aqueous solution containing a silica raw material, the pH of the mixed solution is preferably 1 to 10. Thereby, the specific surface area of the obtained core-shell type silica can be increased. This pH is more preferably 2-6. In the pH adjustment, the pH of the aqueous solution containing the cationic polymer compound modified silica and / or the aqueous solution containing the silica raw material may be adjusted in advance, or the pH may be adjusted by adding an acid to a mixed solution obtained by mixing both aqueous solutions. good.

After adding the aqueous solution containing the silica raw material to the aqueous solution containing the modified silica, the reaction is preferably carried out at room temperature with stirring for 0.25 to 48 hours.
Then, the silica particles attached to the silica raw material are recovered from the aqueous solution after the reaction. For example, the aqueous solution can be recovered by centrifuging at 100-5,000 rpm, washing the precipitate if necessary, and drying. The precipitate can be washed in the order of, for example, water, acetone, and hexane.
Next, the cationic polymer compound is removed from the obtained silica particles attached to the silica raw material to obtain core-shell type silica. The cationic polymer compound can be removed by firing the silica particles attached to the silica raw material. For example, it can be fired at 400 to 700 ° C. for 2 to 24 hours.

In the present invention, a shell layer can be formed on the surface of silica particles by the above steps. The shell layer may be one layer or two or more layers. In the present invention, since one shell layer is thick, the thickness of the entire shell layer can be secured even if the number of laminated shell layers is reduced. As a result, in the core-shell type silica, the number of laminated shell layers can be reduced, and the number of steps required for lamination can be reduced.

Hereinafter, a method of forming two or more shell layers on the surface of silica particles will be described.
The method of forming the first shell layer on the surface of the silica particles is the same as the above-mentioned step. For example, a silica raw material may be attached to modified silica and calcined to obtain silica having one shell layer, and then an amino group may be introduced on the surface of the silica having one shell layer.

When two or more shell layers are formed, the conditions such as the amount of the amine compound, the porris succinimides, the polyamine compound, and the silica raw material used in the first shell layer are as described above.

When two or more shell layers are formed, it is preferable to react the succinimides at 0.01 to 10 parts by mass with respect to 1 part by mass of the silica particles when the succinimides are reacted in each layer.
In particular, in the second and higher shell layers, when the porris succinimides are reacted, the porris succinimides may be reacted in an amount of preferably 2 parts by mass or less, more preferably 1 part by mass or less, based on 1 part by mass of the silica particles. preferable. This value is preferably 0.8 parts by mass or less, more preferably 0.6 parts by mass or less, and may be 0.5 parts by mass or less.
As a result, it is possible to prevent a gap from being generated between the plurality of shell layers.
In the second and higher shell layers, the conditions such as the amount of other amine compounds, succinimides, polyamine compounds, and silica raw materials used may be the same as those of the first shell layer.

The core-shell type silica according to the present invention preferably has the following characteristics. In particular, it is a preferable physical property for liquid chromatography applications.
As the shape of the core-shell type silica, spherical particles are preferable, and spherical particles including a true sphere and an ellipsoid are preferable. In the use of the chromatography carrier, a shape close to a true sphere is preferable from the viewpoint of packing property to the column and suppression of pressure loss during use.

The sphericity of the core-shell silica may be, for example, 0.8 or more, preferably 0.9 or more.
Here, the sphericity is determined by observing the silica particles with a scanning electron microscope (SEM), randomly selecting 100 particles, and measuring the major axis and the minor axis of each silica particle. The major axis) is determined, and it is a value obtained by averaging the sphericity of 100 silica particles.

The average particle size of the core-shell silica is preferably 1 μm or more, more preferably 1.3 μm or more, and further preferably 1.5 μm or more.
On the other hand, the average particle size of the core-shell type silica is preferably 100 μm or less, more preferably 80 μm or less, and further preferably 50 μm or less.
Here, the average particle size of the core-shell type silica is measured by a measuring method by the Coulter counter method.

The diameter of the core portion of the core-shell type silica is preferably 0.1 μm or more, more preferably 1 μm or more.
On the other hand, the diameter of the core portion of the core-shell type silica is preferably 100 μm or less, more preferably 10 μm or less.
The diameter of the core portion is the same as the raw material of the silica core.

The thickness of the entire shell layer of the core-shell type silica may be, for example, in the range of 0.01 to 1 μm, or may be in the range of 0.05 to 0.9 μm.

Here, the core portion of the core-shell type silica, that is, the diameter of the silica core and the diameter of the core-shell type silica are determined by a measuring method by the Coulter counter method. Then, the thickness of the shell layer of the core-shell type silica can be obtained from the following formula.
Thickness of shell layer of core-shell type silica = [(diameter of core-shell type silica)-(diameter of core part of core-shell type silica)] / 2

The ratio (D90 / D10) of the 10% particle size (D10) to the 90% particle size (D90) from the smallest volume-equivalent integrated amount of the particle size distribution of the core-shell type silica is preferable in the Coulter counter method. Is 3 or less, more preferably 2 or less, still more preferably 1.6 or less. When D90 / D10 is 1.6 or less, it is possible to prevent an increase in pressure loss even with core-shell type silica having a small average particle size. Further, D90 / D10 is preferable because the closer it is to 1, the more uniform the particle size distribution is.

Here, D10 is the particle size when the volume of the particle size is integrated from the smaller side of the particle size in the particle size distribution by the Coulter counter method and becomes 10% of the total volume, and D90 is the same. The particle size is such that the integrated volume is 90%. Since D90 / D10 is a ratio of these particle sizes, it can be obtained from D10 and D90 obtained by measuring core-shell type silica with "Multisizer III" manufactured by Beckman Coulter.

The specific surface area of the core-shell silica, in constant-volume Ryoshiki gas adsorption method, is preferably from ^{7m 2} / ^g~500m 2 / g, more preferably ^{7m 2} / ^g~150m 2 / g.
A large specific surface area is preferable because it improves the ability to adsorb the substance to be separated, but if it is too large, it takes time for the substance to be separated to be released, so it is preferable to set it within the above range.

The average pore diameter of the core-shell type silica is preferably 1 nm to 400 nm, more preferably 2 nm to 200 nm, and further preferably 4 nm to 150 nm in the constant volume gas adsorption method. When the average pore diameter is 1 nm or more, the ability to adsorb the substance to be separated is improved, and a large-capacity carrier can be provided. Further, when the average pore diameter is 400 nm or less, it is possible to prevent a decrease in the strength of the core-shell type silica while maintaining a large adsorption amount of the substance to be separated.

The pore volume of the core-shell type silica is preferably 0.01 mL / g or more, more preferably 0.05 mL / g or more, still more preferably 0.1 mL / g or more in constant volume gas adsorption. Is. When the pore volume is 0.01 mL / g or more, the ability to adsorb the substance to be separated is improved, and a large-capacity carrier can be provided. The pore volume is preferably 2 mL / g or less, more preferably 1 mL / g or less, still more preferably 0.5 mL / g or less, from the viewpoint of the strength of the core-shell type silica.

The physical characteristics of the pores obtained by these constant-volume gas adsorption methods can be measured by using "BELSORP-mini II" manufactured by Microtrac Bell Co., Ltd. or the like. These pore physical characteristics are the physical characteristics of the entire core-shell type silica.

The core-shell type silica described above can be used as a chromatography carrier. As the chromatography carrier, a carrier containing the above-mentioned core-shell type silica as a support and having a ligand immobilized on the core-shell type silica can be used.

In the cation exchange chromatography carrier, a sulfonic acid, a carboxyl group, or the like can be used as the ligand.
In the anion exchange chromatography carrier, a primary amine, a secondary amine, a tertiary amine, a quaternary amine and the like can be used as the ligand.
In the reversed-phase chromatography carrier, a long-chain alkyl group, a phenyl group, an alkyl fluoride group and the like can be used as the ligand. As the long-chain alkyl group, an alkyl group having 1 to 30 carbon atoms is preferable, and examples thereof include a methyl group, a butyl group, an octyl group, an octadecyl group and the like.
In the size exclusion chromatography carrier, an aliphatic diol group or the like can be used as the ligand.

When chromatography is performed using the above-mentioned chromatography carrier, the chromatography carrier is packed in a column and used. As the column, a column made of glass, stainless steel, resin or the like can be appropriately used.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto. In the following description, the same components are used.

<Synthesis and purification of porris succinimide (PSI)>
Table 1 shows the synthetic formulations of porris succinimide of Examples 1 to 6.
In Example 1, 40 g of D, L-aspartic acid (Mw = 133.11 g / mol, 0.30 mol) was placed in a crucible and heated at 190 ° C. for 50 hours using an electric furnace. After allowing to cool under reduced pressure, the mixture was crushed using a mill mixer, and 1 L of water was added thereto to form a slurry. This was filtered using a glass filter, washed successively with 1.8 L of water and 1.2 L of acetone, and dried under reduced pressure at room temperature for 5 hours to obtain succinimide.
In Examples 2 to 6, the amount of phosphoric acid (85 vol% aqueous solution) shown in Table 1 was added to 40 g (Mw = 133.11 g / mol, 0.30 mol) of D, L-aspartic acid, and a mortar was used. The mixture was homogenized, placed in a crucible, and heated at 190 ° C. for 50 hours using an electric furnace. After allowing to cool under reduced pressure, the mixture was crushed using a mill mixer, and 1 L of water was added thereto to form a slurry. This was filtered using a glass filter, washed successively with 1.8 L of water and 1.2 L of acetone, and dried under reduced pressure at room temperature for 5 hours to obtain succinimide.
In the table, the molar ratio of phosphoric acid / aspartic acid and the weight average molecular weight (Mw) of the obtained porris succinimide are shown.

The method for measuring the weight average molecular weight is GPC (gel permeation chromatography) using polystyrene as a standard. The measurement conditions of GPC are shown below.
A stainless steel column having an inner diameter of 4.6 mm and a length of 250 mm is filled with Diol-EP-DF-1000AW (manufactured by AGC SITEC), and this column is loaded into a chromatography apparatus "Chromaster (manufactured by Hitachi)". The poris succinimide prepared by -12 was injected into the apparatus, and the weight average molecular weight thereof was measured under the following conditions.
Eluent: 0.1M NaHPO ₄ / Na ₂ HPO ₄ + 0.2M NaCl (pH 7.0).
Flow rate: 0.3 mL / min.
Temperature: 23 ° C.
Detector: UV at 210 nm.
Sample concentration: 0.2% by mass
Injection volume: 20 μL.
Standard sample: TSK GEL standard polystyrene (manufactured by Tosoh Corporation).
For standard polystyrene, a sample having the following weight average molecular weight was used.
A300; molecular weight 453, A1000; molecular weight 1,050, A2500; molecular weight 2,500, A5000; molecular weight 5,870, F1; molecular weight 9,490, F2; molecular weight 17,100, F4; molecular weight 37,200, F10; molecular weight 98,900, F20; molecular weight 189,000, F40; molecular weight 397,000, F80; molecular weight 707,000, F128; molecular weight 1.110,000.

Table 2 shows the purified formulations of porris succinimide of Examples 7 to 12.
In Examples 7 to 12, 10 g of porris succinimide synthesized in Examples 1 to 6 was dissolved in the amount of DMF shown in Table 2, and the amount of acetone shown in Table 2 was gradually added at room temperature to add a high molecular weight poris succinimide. Only reprecipitated. The solution was centrifuged at 3,000 rpm for 10 minutes. After removing the supernatant, 840 mL of acetone was added, filtered using a glass filter, further washed with 30 mL of acetone, dried under reduced pressure at room temperature for 5 hours, and the weight average molecular weight (Mw) shown in Table 2 was determined. Poris succinimide was obtained.
Using this porris succinimide, the following steps were performed.

<Synthesis of core-shell type silica>
The core-shell type silica was synthesized in the following four steps.
(1) Step of reacting an amine compound,
(2) Step of reacting porris succinimide,
(3) Step of reacting ethylenediamine to form modified silica,
(4) A step of electrostatically adsorbing silica sol to modified silica and firing it.

(1) Step of reacting an amine compound "Hypresica FQ-N2N" manufactured by Ube Exsymo Co., Ltd. was used as a raw material for silica particles. The physical characteristics of these silica particles are as follows.
Average particle size = 2.06 μm, uniformity coefficient (D90 / D10) = 1.10, specific surface area = 2.3 m ² / g, pore volume = 0.0066 mL / g.
Here, the average particle size was measured by the Coulter counter method using Multisizer III (manufactured by Beckman Coulter). The uniformity coefficient was determined from the ratio of the D10 particle size and the D90 particle size measured by the same method. The specific surface area and pore volume were measured by the BET method and the BJH method using BELSORP-mini II (manufactured by Microtrac Bell).

Table 3 shows the synthetic formulations of aminopropylated silica of Examples 13-18'.
50 g of silica particles were slurried with 165 mL of toluene. Aminopropylsilane (3-aminopropyltriethoxysilane (“Sila Ace S-330” manufactured by JNC)) in the amount shown in Table 3 was added thereto, and the mixture was reacted at 100 ° C. for 4.5 hours. The silica slurry was filtered using a glass filter, washed successively with 1050 mL of toluene, 350 mL of acetone, and 350 mL of hexane, and then allowed to stand dry at 70 ° C. to synthesize aminopropylated silica.
The following steps were carried out using this aminopropylated silica.
The aminopropylsilane modification density shown in Table 3 is calculated from the input amounts of silica particles and aminopropylsilane.

(2) Steps for Reacting Poris Succinimide Table 4 shows the formulations of each of the steps (1) to (4) in the synthesis of the core-shell silica of Examples 19 to 58, and the specific surface area of the obtained core-shell silica.
To the amount of DMF shown in Table 4, the porris succinimide synthesized in Examples 1 to 12 was added in the amount shown in Table 4 to prepare a porris succinimide solution having the concentration shown in Table 4, respectively. To this, 1 g of aminopropylated silica synthesized in the above step (1) was added, and the mixture was stirred at room temperature for 24 hours. It was filtered and washed with 21 mL of DMF and 7 mL of acetone. Poris succinimide-modified silica was synthesized by drying at room temperature and chemically bonding.
“PSI / AP (molar part)” shown in Table 4 refers to porris succinimide (molar part) “{poris succinimide (molar) / amino introduced into silica particles” with respect to 100 mol parts of aminopropylsilane introduced into silica particles. It was obtained from "group (mol)} x 100".

(3) Step of reacting ethylenediamine to form modified silica 1 g of porris succinimide-modified silica synthesized in the step of (2) above was slurried with 1.6 mL of DMF. The amount of ethylenediamine (EDA) shown in Table 4 was added thereto, and the mixture was stirred at room temperature for 2 hours. This was filtered and washed successively with 21 mL of DMF and 7 mL of acetone. It was dried at room temperature for 1 hour to synthesize modified silica.

(4) Step of Electrostatically Adsorbing Silica Sol on Modified Silica and Firing The modified silica synthesized in the above step (3) was added to water to prepare a silica particle slurry having a solid content concentration of 3.2% by mass. The amounts of silica particles and water are shown in Table 4. The silica particle slurry was adjusted to the pH shown in Table 4 with hydrochloric acid, and then stirred at room temperature for 30 minutes.
On the other hand, the silica sol was diluted with water in another container to prepare a silica sol solution having a solid content concentration of 4.8% by mass. Table 4 shows the particle size of the silica sol, the amount used, and the amount of water. This silica sol solution was adjusted with hydrochloric acid so as to have a pH similar to that of the silica particle slurry shown in Table 4, and added to the silica particle slurry. The mixed solution was stirred at room temperature for the time shown in Table 4.
This is centrifuged at 1,000 rpm for 10 minutes to remove the supernatant, and then washed sequentially with 50 mL / g-silica of water (50 mL of water is used per 1 g of silica. The same applies hereinafter) and 30 mL / g-silica of acetone. Then, it was dried under reduced pressure for 30 minutes at room temperature. This dried product was calcined at 600 ° C. for 4 hours to obtain core-shell type silica.
The specific surface area of the obtained core-shell type silica was measured by a constant-volume gas adsorption method and is shown in Table 4.

The details of the silica sol are as follows.
Silica sol with a particle size of 17 nm: "Quatron PL-2L" manufactured by Fuso Chemical Industry Co., Ltd., solid content 20% by mass.
Silica sol with a particle size of 6 to 8 nm: "Quatron PL-06L" manufactured by Fuso Chemical Industry Co., Ltd., solid content 6% by mass.
Silica sol with a particle size of 4 nm: "Snowtex ST-OXS" manufactured by Nissan Chemical Industries, Ltd., solid content 10% by mass.
Silica sol with a particle size of 10 nm: "Snowtex ST-O" manufactured by Nissan Chemical Industries, Ltd., solid content 20% by mass.

As shown in Table 4, in Examples 19 to 26, the pHs of the silica particle slurry and the silica sol were changed in the step (4), and the ratio of the core-shell type silica obtained was in the range of about pH 4.6 to 6.1. The surface area was as good as about ^{20 m 2 / g.}
In Examples 29 and 36, the aminopropylsilane modification density was higher in step (1) than in Example 27, and the amount of porris succinimide used in step (2) was higher than that in Example 28. The surface area has also increased.
In Examples 30 to 33, the aminopropylsilane modification density was changed in step (1), and the aminopropylsilane modification density of Example 32 was 2.2 μmol / m ² , and the specific surface area of the obtained core-shell silica was large. I understood.
In Example 29, Example 32, Example 34, and Example 35, the PSI molecular weight was changed in step (2), and the ratio of the core-shell type silica obtained at the PSI molecular weights of 106,000 and 131,000 of Examples 29 and 32 was obtained. It was found that the surface area was large.

In Examples 37 to 42, the particle size of the silica sol was set to 6 nm in step (4), and the pHs of the silica particle slurry and the silica sol were changed, and the core-shell type silica obtained in the range of pH 4.4 to 5.6 was obtained. It was found that the specific surface area of silica was large.
In Examples 43 to 51, the particle size of the silica sol is set to 4 nm in step (4), and the pHs of the silica particle slurry and the silica sol are changed, and the core-shell type silica obtained in the range of pH 2.8 to 3.7 is obtained. It was found that the specific surface area of silica was large.
In Examples 52 to 58, the particle size of the silica sol is set to 10 nm in step (4), and the pHs of the silica particle slurry and the silica sol are changed, and the core-shell type silica obtained in the range of pH 2.5 to 3.7 is obtained. It was found that the specific surface area of silica was large.

In Example 32, Example 38 to Example 58, the AP modification density was the same in the step (1), the molecular weight and the amount of the porris succinimide used were the same in the step (2), and the particle size of the silica sol was changed in the step (4). doing. Through these, a preferable specific surface area was obtained for the silica sol having each particle size. From this, it was possible to prepare a core-shell type silica having a desired pore size using silica sol having each particle size.

<Lamination of shell layers>
Table 5 shows the formulations of Examples 59 to 66 in which the shell layers were laminated twice.
In each example, first, the first layer of the shell layer was prepared by using the same formulation as in Example 32 and using the same method as in steps (1) to (4) above. After firing the first layer, the second layer of the shell layer was subsequently prepared by the same method as in steps (1) to (4) above according to the same formulation shown in Table 5.

With respect to the obtained core-shell type silica in which two shell layers were laminated, the presence or absence of an empty layer between the shell layers was evaluated as follows.
First, the pore distribution of the core-shell silica was measured at the stage of forming the first shell layer, and then the pore distribution of the core-shell silica was measured at the stage of forming the second shell layer.
The pore distribution of the first layer and the pore distribution of the second layer were overlapped, and it was observed whether or not the pore distribution of the second layer had a bulge in the range of the pore diameter larger than the peak top. In each example of Table 5, since the silica sol having a particle size of 17 nm is used in the step (4), the peak top appears in the pore distribution of the first layer and the second layer near the pore diameter of 17 nm, but the second layer. The presence or absence of an empty layer was determined based on whether or not a broad peak was observed in the pore distribution in the pore diameter range of 30 to 80 nm.
The pore distribution of the core-shell type silica was measured by the constant volume gas adsorption method. The adsorption process of the BJH method was adopted as the analysis of the evaluation method (mesopores) for the presence or absence of the air layer.

As shown in Table 5, in Examples 59 to 62, the aminopropylsilane modification density was changed in the step (1), and when the aminopropylsilane modification density was 0.2 μmol / m ² or more, the obtained core-shell type silica was used. A gap was observed in the shell layer.
In Example 63 and Example 64, the amount of porris succinimide used was reduced in the step (2) as compared with Example 60, and it was observed that there was no gap between the shell layers in the obtained core-shell type silica.
In Example 65 and Example 66, the amount of porris succinimide used in step (2) was smaller than that in Example 62, and in Example 65, the amount of porris succinimide used was 0.01 g / g-silica, and the obtained core-shell type silica was used for the shell. It was observed that there were no gaps between the layers.
In Examples 59 to 66, core-shell silica having a sufficient specific surface area was obtained regardless of the presence or absence of an empty layer.

Table 5 shows the formulations of Example 67 in which the shells were laminated 5 times and Example 68 in which the shells were laminated 7 times.
In Example 67 and Example 68, the amount of silica particles charged in the first lamination was 30 g. The washing after filtration in step (3) was performed in the order of DMF 30 mL / g-silica, water 50 mL / g-silica, hydrochloric acid 50 mL / g-silica, water 50 mL / g-silica, and acetone 30 mL / g-silica.
Other than this, in Example 67, the shell layers of the 1st to 5th layers were prepared in the same manner as in Example 62 above according to the formulation shown in Table 5.
In addition to this, in Example 68, the first shell layer was prepared in the same manner as in Example 32, and the second to seventh shell layers were prepared in the same manner as in Example 65, according to the formulation shown in Table 5.
Table 5 shows the formulation of Example 74 in which the shells were laminated eight times.
In Example 74, silica particles having the following physical property values were used as the raw material for the silica particles in step (1).
Average particle size = 1.77 μm, uniformity coefficient (D90 / D10) = 1.13, specific surface area = 1.8 m ² / g, pore volume = 0.0042 mL / g. The amount of silica particles charged in the first lamination was 30 g. In step (4), the particle size of the silica sol was set to 8 nm. Other than that, according to the formulation shown in Table 5, the first shell layer was prepared in the same manner as in Example 32, and the second to eighth shell layers were prepared in the same manner as in Example 65.

Regarding the core-shell type silica in which the obtained multilayer shell layers were laminated, whether or not there was an empty layer between the shell layers was evaluated as follows. Others were measured in the same manner as in Examples 59 to 66 above.
First, the pore distribution of the core-shell type silica is measured at the stage where the first shell layer is formed, and then the pore distribution of the core-shell type silica is measured at the stage where each layer is formed in the same manner for the second and subsequent layers. bottom.
The pore distribution of the first layer and the pore distribution of the outermost layer were overlapped, and it was observed whether or not there was a bulge in the range of the pore diameter larger than the peak top. In each example of Table 5, since a silica sol having a particle size of 17 nm or 8 nm is used in step (4), a peak top appears in the pore distribution of the first layer and the outermost layer at a pore diameter of around 17 nm or 8 nm. The presence or absence of an empty layer was determined based on whether or not a broad peak was observed in the pore size distribution of the surface layer in the pore diameter range of 30 to 80 nm.

As shown in Table 5, in Examples 68 and 74, the amount of PSI used in the step (2) was reduced in the second and subsequent shell layers as compared with Example 67, and the obtained core-shell type silica was used to reduce the gap between the shell layers. Was observed to be absent.
In Examples 67, 68 and 74, with or without an air layer, core-shell silica with sufficient specific surface area was obtained. In addition, it was observed that as the number of layers increased, the specific surface area increased and the shell layer became thicker.

<Amount of porris succinimide (PSI)>
Table 6 shows the formulations of Examples 69 to 73 in which the amount of porris succinimide used was changed in step (2).
In each example, a shell layer was formed on the silica particles by using the same method as in the above steps (1) to (4) to prepare a core-shell type silica having one shell layer.

As shown in Table 6, in the range of Examples 69 to 73, core-shell type silica having a sufficient specific surface area was obtained regardless of the amount of porris succinimide used.

<SEM observation>
SEM (scanning electron microscope) observation was performed as follows.
FIG. 1 is a cross-sectional photograph of the core-shell type silica of Example 67.
FIG. 2 is a cross-sectional photograph of the core-shell type silica of Example 68, in which (a) is 25,000 times and (b) is 100,000 times.
FIG. 3 is a cross-sectional photograph of the core-shell type silica of the reference example.
FIG. 4 is an overall photograph of the core-shell type silica of (a) Example 68 and (b) Reference Example.
As the core-shell type silica of the reference example, Agilent's "Poroshell 120 EC-C18 (particle size: 2.7 μm)" was fired at 600 ° C. for 8 hours.

No empty layer was observed in the core-shell silica of Example 68 and Reference Example as compared with the core-shell silica of Example 67.
Further, from FIG. 4, it can be seen that the core-shell type silica of Example 68 has a uniform surface and a higher sphericity than the core-shell type silica of the reference example.

<Pore properties>
Table 7 shows the pore physical characteristics of Example 67, Example 68, Example 74 and Reference Example.
As shown in Table 7, the core-shell type silicas of Examples 67 and 68 had a large particle size because the shell layer could be thickened, and had a sufficient specific surface area and pore volume.
Here, the particle size was measured by the Coulter method, and the specific surface area, the pore volume, and the pore diameter were measured by the constant volume gas adsorption method.

Further, FIG. 5 shows the pore distribution of the pore physical characteristics of Examples 67, 68, and Reference Example.
As shown in FIG. 5, in Examples 68 and 74, no broad peak was observed at 30 to 80 nm, and as can be seen from the above SEM observation, it was confirmed that there was no empty layer in Example 68. This was the same for the reference example. In Example 67, a broad peak was observed at 30 to 80 nm, and the presence of an empty layer was observed as can be seen from the above SEM observation.

<Theoretical height evaluation>
Van Deemter plots were obtained using the core-shell silica of Example 67, Example 68, Example 74, and Reference. FIG. 6 shows a van Deemter plot.
As shown in FIG. 6, in Example 68 and Example 74, the theoretical step height was smaller than that in Example 67, and the separation efficiency was further improved. In addition, Example 68 was equivalent to the van Deemter plot of the reference example. Further, in Example 74, the theoretical step height was smaller than that in the reference example, and the separation efficiency was excellent.

(Van Deemter plot evaluation using HPLC)
The measurement method of the van Deemter plot is as follows.
After each core-shell type silica is modified with ODS (octadecylsilyl), it is filled in a stainless steel column having an inner diameter of 4.6 mm and a length of 100 mm, and this column is loaded into a chromatography device "Chromaster HITACHI" and measured under the following conditions. bottom.
Eluent: acetonitrile / water = 65/35.
Temperature: 25 ° C.
Detector: UV at 254 nm.
Sample: Naphthalene (manufactured by Kanto Chemical Co., Inc.).

The theoretical plate number of naphthalene was measured at each flow velocity using a column filled with each core-shell type silica. For the detected peak, the number of theoretical plates was calculated by the following calculation according to the calculation method of DAB (German Pharmacopoeia).
N = 5.54 × [t / W _0.5 ] ²
Here, N is the number of theoretical plates, t is the retention time of the component, and W _0.5 is the peak width at the position of 50% of the peak height.
The theoretical step height HETP was obtained from the theoretical arithmetic N by the following calculation.
HETP = N / L
Here, L is the column length.
FIG. 6 is a van Deemter plot in which the theoretical step height HETP at each linear flow velocity u [cm / sec] is plotted.

Claims (8)

After reacting the amine compound on the surface of the silica particles, the polymer compound having a succinimide skeleton is reacted, and the polyamine compound is reacted to obtain modified silica modified with the cationic polymer compound.
A method for producing core-shell type silica, wherein a silica raw material is attached to the modified silica, and a cationic polymer compound is removed by firing to obtain a silica shell layer. The method for producing core-shell type silica according to claim 1, wherein the silica particles are solid silica. The method for producing core-shell type silica according to claim 1 or 2 , wherein the amine compound is reacted so as to be ^{0.05 to 4 μmol / m 2} per surface area of the silica particles. The method for producing core-shell type silica according to any one of claims 1 to 3 , wherein the polymer compound having a succinimide skeleton is reacted with 1 part by mass of the silica particles in an amount of 10 parts by mass or less. The method for producing core-shell silica according to any one of claims 1 to 4 , wherein the polymer compound having a succinimide skeleton has a weight average molecular weight of 5,000 to 500,000. The method for producing core-shell silica according to any one of claims 1 to 5 , wherein the polyamine compound is an aliphatic diamine compound. The method for producing core-shell type silica according to any one of claims 1 to 6 , wherein the modified silica and the silica raw material are adjusted to pH 1 to pH 10 in a solvent, and the silica raw material is adhered to the modified silica. .. A core-shell type silica is obtained by the production method according to any one of claims 1 to 7.
After reacting the amine compound on the surface of the core-shell type silica, the polymer compound having a succinimide skeleton is reacted, and the polyamine compound is reacted to obtain modified silica modified with the cationic polymer compound.
A method for producing core-shell type silica having a plurality of shell layers, wherein a silica raw material is attached to the modified silica, the cationic polymer compound is removed by firing, and the outermost silica shell layer is obtained.

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