JP2016044091A - Mesoporous silica particle coated with nonporous silica, and method for producing the same - Google Patents
Mesoporous silica particle coated with nonporous silica, and method for producing the same Download PDFInfo
- Publication number
- JP2016044091A JP2016044091A JP2014168496A JP2014168496A JP2016044091A JP 2016044091 A JP2016044091 A JP 2016044091A JP 2014168496 A JP2014168496 A JP 2014168496A JP 2014168496 A JP2014168496 A JP 2014168496A JP 2016044091 A JP2016044091 A JP 2016044091A
- Authority
- JP
- Japan
- Prior art keywords
- silica
- particles
- dispersion
- mesopores
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Silicates, Zeolites, And Molecular Sieves (AREA)
Abstract
Description
本発明は、粒子外周部が無孔質シリカによって被覆されたメソポーラスシリカ粒子、その分散液及びその製造方法に関する。 The present invention relates to mesoporous silica particles whose outer periphery is coated with nonporous silica, a dispersion thereof, and a method for producing the same.
メソポーラスシリカ粒子は、高い表面積や大きな細孔容積（粒子内部の空隙）を持つため、様々な応用が期待されている。例えば、薬剤のキャリアとしてのドラッグデリバリーや、色素導入によるバイオイメージングなどの医療分野での応用、また、樹脂と複合化することによる低反射率（Ｌｏｗ−ｎ）、低誘電率（Ｌｏｗ−ｋ)、低熱伝導率材料などへ
の応用が検討されている。これらの応用の多くでは、粒子表面に存在する開孔部の存在により、内包物の溶出や粒子内部への樹脂侵入（即ち、空隙率低下）による性能低下の恐れがあった。従って、粒子の内部空隙を残しつつ、粒子表面の孔を塞ぐ技術が重要視されてきた。
Since mesoporous silica particles have a high surface area and a large pore volume (voids inside the particles), various applications are expected. For example, drug delivery as a drug carrier, application in medical fields such as bioimaging by introducing a dye, and low reflectivity (Low-n) and low dielectric constant (Low-k) by combining with a resin Application to low thermal conductivity materials is being studied. In many of these applications, the presence of pores present on the surface of the particle may cause a decrease in performance due to elution of inclusions or penetration of the resin into the particle (ie, a decrease in porosity). Therefore, a technique for closing the pores on the particle surface while leaving the internal voids of the particle has been regarded as important.
ナノ粒子やポリマーなどを用いてメソ孔を塞ぐ以下の技術が報告されているが、効率的かつ確実に孔を塞ぐことは困難であった。
非特許文献１には、ＣｄＳなどのナノ粒子を用いて孔を塞ぐ技術が報告されているが、粒子表面の開孔部すべてを同時に塞ぐことは困難である。
非特許文献２には、粒子表面にポリマーをグラフトして孔を塞ぐ技術が報告されているが、合成に高度な技術を要し、また、粒子の表面状態が変わるために粒子が凝集する可能性がある。さらに、有機物で被覆するために耐熱性が低いという問題がある。
特許文献１には、大口径のメソポーラスシリカ粒子の表面をより小さな孔を有するメソポーラスシリカで被覆する技術が報告されているが、被覆層に存在する細孔のため外部からの樹脂の侵入や内包物の溶出を完全には抑制できない。また、特許文献１ではメソ孔を有する粒子の合成時に使用した界面活性剤を除去しないまま粒子外周部を被覆するため、界面活性剤を除去するために被覆層を多孔質とする必要があった。
The following techniques for plugging mesopores using nanoparticles or polymers have been reported, but it has been difficult to efficiently and reliably close the pores.
Non-Patent Document 1 reports a technique for closing holes using nanoparticles such as CdS, but it is difficult to simultaneously close all the openings on the particle surface.
Non-Patent Document 2 reports a technology for grafting a polymer onto the particle surface to close the pores, but it requires advanced technology for synthesis, and the particles can aggregate because the surface state of the particle changes. There is sex. Furthermore, since it coats with organic substance, there exists a problem that heat resistance is low.
Patent Document 1 reports a technique for coating the surface of large-diameter mesoporous silica particles with mesoporous silica having smaller pores. However, since the pores exist in the coating layer, the penetration and inclusion of resin from the outside are reported. The elution of objects cannot be completely suppressed. Further, in Patent Document 1, since the outer periphery of the particle is coated without removing the surfactant used in the synthesis of the particles having mesopores, it is necessary to make the coating layer porous in order to remove the surfactant. .
また、従来技術には、界面活性剤を除去したメソ孔を有する粒子の外周部を被覆しようとするとメソ孔自体が閉塞して空隙率が低下するという問題もある。 In addition, the conventional technique has a problem that when the outer peripheral portion of the particles having mesopores from which the surfactant is removed is to be coated, the mesopores themselves are blocked and the porosity is lowered.
本発明は、メソポーラスシリカ粒子を凝集させることなく、粒子内細孔を残したまま粒子外周部の開孔部を被覆して閉孔したメソポーラスシリカ粒子、その分散液及びその製造方法を提供することを目的とする。 The present invention provides a mesoporous silica particle which is closed by covering the open part of the outer periphery of the particle while aggregating the mesoporous silica particle while leaving the pores in the particle, a dispersion thereof, and a method for producing the same. With the goal.
本発明者は、鋭意検討の結果、溶媒中で分散状態のメソポーラスシリカ粒子に含まれる、合成時に使用された界面活性剤を完全に除去した後、粒子外周部を被覆処理することで、粒子内部のメソ孔を保持したまま外周部のみを無孔質シリカで被覆されたメソポーラスシリカ粒子、及び分散液が得られること見出した。なお、本明細書では、機能性物質とは、メソ孔を有するシリカ粒子のメソ孔内に充填することが可能でメソ孔内でその機能を発現できる物質をいう。 As a result of intensive studies, the inventor has completely removed the surfactant used in the synthesis contained in the mesoporous silica particles dispersed in the solvent, and then coated the outer peripheral portion of the particles, so that the inside of the particles It was found that mesoporous silica particles in which only the outer peripheral portion was coated with nonporous silica and a dispersion liquid were obtained while retaining the mesopores. In the present specification, the functional substance refers to a substance that can be filled in the mesopores of silica particles having mesopores and can exhibit the function in the mesopores.
すなわち、本発明を達成する第１観点として、粒子外周部が３〜３０ｎｍの厚さの無孔質シリカで被覆され、３０〜３００ｎｍの一次粒子径を有し、且つ粒子内に２〜１０ｎｍのメソ孔を有するメソポーラスシリカ粒子であり、
第２観点として、第１観点に記載のメソポーラスシリカ粒子が分散媒中に分散されたメソポーラスシリカ粒子分散液であり、
第３観点として、界面活性剤及びｐＨ調整剤を含む水溶液にシリカ源（ａ）を添加して粒子内に２〜１０ｎｍのメソ孔を有するシリカ粒子の分散液を作製した後、界面活性剤を除去する（Ａ）工程、並びに
前記（Ａ）工程で得られたメソ孔を有するシリカ粒子の分散液にｐＨ調整剤を加えてｐＨ８〜１０に調整した後、シリカ源（ｂ）を加え、撹拌下で２０〜９０℃、１〜４８時間処理してメソ孔を有するシリカ粒子の外周部を３〜３０ｎｍの厚さの無孔質シリカで被覆する（Ｂ）工程
を含む、第２観点に記載のメソポーラスシリカ粒子分散液の製造方法であり、
第４観点として、前記シリカ源（ａ）及びシリカ源（ｂ）が、式（Ｉ）で表される珪素アルコキシドである、第３観点に記載のメソポーラスシリカ粒子分散液の製造方法
式（Ｉ） Ｓｉ（ＯＲ1）4
［式（Ｉ）中、Ｒ1は炭素原子数１〜４の直鎖又は分岐のアルキル基を表す。］
であり、
第５観点として、前記シリカ源（ａ）及びシリカ源（ｂ）が、式（ＩＩ）で表される珪素アルコキシド、又は式（Ｉ）及び式（ＩＩＩ）で表される珪素アルコキシドの混合物である、第３観点に記載のメソポーラスシリカ粒子分散液の製造方法
式（ＩＩ） （Ｒ2Ｏ）3Ｓｉ−Ｒ3−Ｓｉ（ＯＲ4）3
［式（ＩＩ）中、Ｒ2及びＲ4は炭素原子数１〜４の直鎖又は分岐のアルキル基を表し、Ｒ3は炭素原子数１〜１０の直鎖状若しくは分岐状の２価の飽和炭化水素基若しくは不飽和
炭化水素基、又は置換基を有していてもよい、炭素原子数６〜３０のアリーレン基若しくはヘテロアリーレン基を表す。］
式（Ｉ） Ｓｉ（ＯＲ1）4
［式（Ｉ）中、Ｒ1は炭素原子数１〜４の直鎖又は分岐のアルキル基を表す。］
式（ＩＩＩ） Ｒ5Ｓｉ（ＯＲ6）3
［式（ＩＩＩ）中、Ｒ5は炭素原子数１〜８の直鎖状若しくは分岐状のアルキル基、又は
置換基を有していてもよい炭素原子数６〜３０のアリール基を表し、Ｒ6は炭素原子数１
〜４の直鎖又は分岐のアルキル基を表す。］
であり、
第６観点として、前記（Ａ）工程中の界面活性剤の除去が、純水、酢酸及びエタノールからなる群から選ばれる少なくとも１種を用いた透析で行われる、第３観点乃至第５観点のいずれか一つに記載のメソポーラスシリカ粒子分散液の製造方法であり、
第７観点として、界面活性剤及びｐＨ調整剤を含む水溶液にシリカ源（ａ）を添加して粒子内に２〜１０ｎｍのメソ孔を有するシリカ粒子の分散液を作製した後、界面活性剤を除去する（Ａ）工程、
前記（Ａ）工程で得られたメソ孔を有するシリカ粒子の分散液に有機化合物又はポリマーを加えて、当該メソ孔の少なくとも一部に有機化合物又はポリマーが充填した複合シリカ粒子の分散液を作製する（Ｃ）工程、並びに
前記（Ｃ）工程で得られた複合シリカ粒子の分散液にｐＨ調整剤を加えてｐＨ８〜１０
に調整した後、シリカ源（ｂ）を加え、撹拌下で２０〜９０℃、１〜４８時間処理して複合シリカ粒子の外周部を３〜３０ｎｍの厚さの無孔質シリカで被覆する（Ｄ）工程
を含む、粒子外周部が３〜３０ｎｍの厚さの無孔質シリカで被覆され、３０〜３００ｎｍの一次粒子径を有し、且つ粒子内に２〜１０ｎｍのメソ孔を有する、機能性物質担持メソポーラスシリカ粒子分散液の製造方法
である。
なお、本明細書では、機能性物質とは、メソ孔を有するシリカ粒子のメソ孔内に充填することが可能でメソ孔内でその機能を発現できる物質をいう。
That is, as a first aspect for achieving the present invention, the outer peripheral portion of the particle is coated with nonporous silica having a thickness of 3 to 30 nm, has a primary particle diameter of 30 to 300 nm, and 2 to 10 nm in the particle. Mesoporous silica particles having mesopores,
As a second aspect, a mesoporous silica particle dispersion in which the mesoporous silica particles described in the first aspect are dispersed in a dispersion medium,
As a third aspect, after adding a silica source (a) to an aqueous solution containing a surfactant and a pH adjuster to prepare a dispersion of silica particles having 2-10 nm mesopores in the particles, the surfactant is added. Step (A) to be removed, and after adjusting the pH to 8 to 10 by adding a pH adjuster to the dispersion of silica particles having mesopores obtained in Step (A), the silica source (b) is added and stirred. In the second aspect, including the step (B) of coating the outer peripheral portion of the silica particles having mesopores with nonporous silica having a thickness of 3 to 30 nm after being treated at 20 to 90 ° C. for 1 to 48 hours. Is a method for producing a mesoporous silica particle dispersion of
As a fourth aspect, the method for producing a mesoporous silica particle dispersion according to the third aspect, wherein the silica source (a) and the silica source (b) are silicon alkoxides represented by the formula (I): Si (OR 1 ) 4
[In the formula (I), R 1 represents a linear or branched alkyl group having 1 to 4 carbon atoms. ]
And
As a fifth aspect, the silica source (a) and the silica source (b) are a silicon alkoxide represented by the formula (II) or a mixture of silicon alkoxides represented by the formula (I) and the formula (III). And a method for producing a mesoporous silica particle dispersion described in the third aspect Formula (II) (R 2 O) 3 Si—R 3 —Si (OR 4 ) 3
[In formula (II), R 2 and R 4 represent a linear or branched alkyl group having 1 to 4 carbon atoms, and R 3 represents a linear or branched divalent group having 1 to 10 carbon atoms. It represents a saturated hydrocarbon group or an unsaturated hydrocarbon group, or an arylene group or heteroarylene group having 6 to 30 carbon atoms, which may have a substituent. ]
Formula (I) Si (OR 1 ) 4
[In the formula (I), R 1 represents a linear or branched alkyl group having 1 to 4 carbon atoms. ]
Formula (III) R 5 Si (OR 6 ) 3
[In formula (III), R 5 represents a linear or branched alkyl group having 1 to 8 carbon atoms, or an aryl group having 6 to 30 carbon atoms which may have a substituent, and R 6 is 1 carbon atom
-4 linear or branched alkyl groups are represented. ]
And
As a sixth aspect, the removal of the surfactant during the step (A) is performed by dialysis using at least one selected from the group consisting of pure water, acetic acid and ethanol. A method for producing a mesoporous silica particle dispersion according to any one of the above,
As a seventh aspect, after adding a silica source (a) to an aqueous solution containing a surfactant and a pH adjuster to produce a dispersion of silica particles having 2-10 nm mesopores in the particles, the surfactant is added. (A) process to remove,
An organic compound or polymer is added to the dispersion of silica particles having mesopores obtained in the step (A) to produce a dispersion of composite silica particles in which at least a part of the mesopores is filled with the organic compound or polymer. Step (C), and adding a pH adjuster to the dispersion of the composite silica particles obtained in step (C) to adjust the pH to 8 to 10
Then, the silica source (b) is added, and the outer periphery of the composite silica particles is coated with nonporous silica having a thickness of 3 to 30 nm by treating with stirring at 20 to 90 ° C. for 1 to 48 hours ( D) A function including a step in which the outer peripheral portion of the particle is coated with nonporous silica having a thickness of 3 to 30 nm, has a primary particle diameter of 30 to 300 nm, and has 2 to 10 nm of mesopores in the particle. This is a method for producing a mesoporous silica particle dispersion liquid.
In the present specification, the functional substance refers to a substance that can be filled in the mesopores of silica particles having mesopores and can exhibit the function in the mesopores.
本発明によれば、メソポーラスシリカ粒子を凝集させることなく、粒子内細孔を残したまま粒子外周部の開孔部を被覆して閉孔することができる。また、分散媒中に分散したメソポーラスシリカ粒子に対して、珪素アルコキシドを所定のｐＨ条件下で添加することによって、表面の開孔部を塞ぐことが可能である。そして、開孔部の被覆工程を行ってもメソポーラスシリカ粒子の良好な分散性を保持することができる。 According to the present invention, without opening the mesoporous silica particles, it is possible to cover and close the pores on the outer periphery of the particles while leaving the pores in the particles. Further, by adding silicon alkoxide to the mesoporous silica particles dispersed in the dispersion medium under a predetermined pH condition, it is possible to close the pores on the surface. And even if it performs the covering process of the opening, good dispersibility of the mesoporous silica particles can be maintained.
（コア粒子分散液）
本発明のメソポーラスシリカ粒子は、メソ孔を有するコア粒子と粒子外周部を被覆する無孔質シリカで構成される。メソ孔を有するコア粒子は、公知技術によって作製される開孔部を有するメソポーラスシリカ粒子を用いることができる。
(Core particle dispersion)
The mesoporous silica particles of the present invention are composed of core particles having mesopores and nonporous silica covering the outer periphery of the particles. As the core particles having mesopores, mesoporous silica particles having an opening produced by a known technique can be used.
メソ孔を有するコア粒子は窒素吸着法（ＢＥＴ法）比表面積が４００〜１５００ｍ2／
ｇであり、２〜１０ｎｍのメソ孔を有し、細孔容積が０．５〜３．０ｍｌ／ｇであることが好ましい。また、透過型電子顕微鏡（ＴＥＭ）観察により測定したメソポーラスシリカ粒子の１次粒子径は３０〜３００ｎｍであり、動的光散乱法によって測定される分散粒子径は３０〜３００ｎｍであることが好ましい。
Core particles having mesopores have a nitrogen adsorption method (BET method) specific surface area of 400-1500 m 2 /
g, having 2 to 10 nm mesopores, and preferably having a pore volume of 0.5 to 3.0 ml / g. The primary particle diameter of the mesoporous silica particles measured by transmission electron microscope (TEM) observation is preferably 30 to 300 nm, and the dispersed particle diameter measured by the dynamic light scattering method is preferably 30 to 300 nm.
メソ孔を有するコア粒子は、例えば、Ｈ．Ｙａｍａｄａ ｅｔ ａｌ．，Ｃｈｅｍ．Ｍａｔｅｒ．，２４，１４６２（２０１２）を参考に作製することができる。同文献によれば、鋳型となる界面活性剤を含有した純水中にテトラプロポキシシランを添加し、８０℃で所定時間攪拌を行った後、鋳型の界面活性剤を透析により除去することによりメソ孔を有する多孔質シリカ粒子の分散液を得ることができる。 The core particles having mesopores are, for example, H.P. Yamada et al. , Chem. Mater. , 24, 1462 (2012). According to this document, tetrapropoxysilane is added to pure water containing a surfactant as a template, stirred for a predetermined time at 80 ° C., and then the template surfactant is removed by dialysis. A dispersion of porous silica particles having pores can be obtained.
本発明において、前記のメソポーラスシリカ粒子が分散媒中に分散されたメソポーラスシリカ粒子分散液は、次の（Ａ）工程及び（Ｂ）工程を含む方法により製造することができる。
（Ａ）工程：界面活性剤及びｐＨ調整剤を含む水溶液にシリカ源（ａ）を添加して粒子内に２〜１０ｎｍのメソ孔を有するシリカ粒子の分散液を作製した後、界面活性剤を除去する工程、
（Ｂ）工程：前記（Ａ）工程で得られたメソ孔を有するシリカ粒子の分散液にｐＨ調整剤を加えてｐＨ８〜１０に調整した後、シリカ源（ｂ）を加え、撹拌下で２０〜９０℃、１〜４８時間処理してメソ孔を有するシリカ粒子の外周部を３〜３０ｎｍの厚さの無孔質シリカで被覆する工程。
In the present invention, the mesoporous silica particle dispersion in which the mesoporous silica particles are dispersed in a dispersion medium can be produced by a method including the following steps (A) and (B).
Step (A): A silica source (a) is added to an aqueous solution containing a surfactant and a pH adjuster to prepare a dispersion of silica particles having 2 to 10 nm mesopores in the particles, and then the surfactant is added. Removing,
Step (B): After adding a pH adjuster to the dispersion of silica particles having mesopores obtained in Step (A) to adjust to pH 8 to 10, the silica source (b) is added, and the mixture is stirred for 20 The process which coat | covers the outer peripheral part of the silica particle which has -90 degreeC and 1-48 hours, and has a mesopore for 3-30 nm in thickness.
（界面活性剤の除去）
本発明で実施される界面活性剤の除去操作は、透析、溶媒抽出、酸処理等の公知の方法を用いることができるが、透析により行うことが好ましい。
(Removal of surfactant)
The surfactant removal operation performed in the present invention can be performed by a known method such as dialysis, solvent extraction, acid treatment, etc., but is preferably performed by dialysis.
透析は、既存の透析膜を用いることができる。例えば、鋳型となる界面活性剤を含有し
たメソポーラスシリカ粒子分散液に対して、体積比で１０〜１００倍の抽出溶媒を用いて実施される。また、抽出溶媒には、純水、酢酸及びエタノールからなる群から選ばれる少なくとも１種を用いることができる。抽出溶媒としては、これらの混合溶媒を用いることがより好ましい。
For dialysis, an existing dialysis membrane can be used. For example, it is carried out using an extraction solvent 10 to 100 times in volume ratio with respect to a mesoporous silica particle dispersion containing a surfactant as a template. Moreover, at least 1 sort (s) chosen from the group which consists of a pure water, an acetic acid, and ethanol can be used for an extraction solvent. As the extraction solvent, it is more preferable to use a mixed solvent thereof.
透析は、鋳型である界面活性剤を完全に除去するために複数回実施することが好ましく、異なる抽出溶媒を組み合わせて複数回実施することがより好ましい。透析によって界面活性剤が除去されたことは、ＣＨＮ分析によって炭素原子が検出限界以下であることを確認することにより確かめることができる。 Dialysis is preferably performed a plurality of times in order to completely remove the surfactant as a template, and more preferably performed a plurality of times in combination with different extraction solvents. The removal of the surfactant by dialysis can be confirmed by confirming that the carbon atom is below the detection limit by CHN analysis.
（粒子外周部の被覆）
本発明でメソ孔を有するコア粒子を無孔質シリカで被覆する際は、まず水又は親水性の有機溶媒にメソ孔を有するコア粒子が分散されたものを用意し、次いでこの分散液のｐＨを８〜１０に調整する。この時、該分散液のｐＨ調整剤としては、トリエタノールアミン、トリエチルアミン、アンモニア及び水酸化ナトリウムなどの塩基を用いることができる。続いて、無孔質シリカのシリカ源として、珪素アルコキシドを該分散液に添加して、無孔質シリカでメソ孔を有するコア粒子を被覆する。
(Coating of particle periphery)
When the core particles having mesopores are coated with nonporous silica in the present invention, first, the core particles having mesopores dispersed in water or a hydrophilic organic solvent are prepared, and then the pH of this dispersion liquid is prepared. Is adjusted to 8-10. At this time, a base such as triethanolamine, triethylamine, ammonia and sodium hydroxide can be used as a pH adjuster of the dispersion. Subsequently, as a silica source for nonporous silica, silicon alkoxide is added to the dispersion to coat the core particles having mesopores with nonporous silica.
被覆に使用される珪素アルコキシドとしては、下記の式（Ｉ）で表される珪素アルコキシドであることが好ましい。
式（Ｉ） Ｓｉ（ＯＲ1）4
［式（Ｉ）中、Ｒ1は炭素原子数１〜４の直鎖又は分岐のアルキル基を表す。］
また、被覆に使用される珪素アルコキシドとしては、下記の式（ＩＩ）で表される珪素アルコキシドであることが好ましい。
式（ＩＩ） （Ｒ2Ｏ）3Ｓｉ−Ｒ3−Ｓｉ（ＯＲ4）3
［式（ＩＩ）中、Ｒ2及びＲ4は炭素原子数１〜４の直鎖又は分岐のアルキル基を表し、Ｒ3は炭素原子数１〜１０の直鎖状若しくは分岐状の２価の飽和炭化水素基若しくは不飽和
炭化水素基、又は置換基を有していてもよい、炭素原子数６〜３０のアリーレン基若しくはヘテロアリーレン基を表す。］
The silicon alkoxide used for the coating is preferably a silicon alkoxide represented by the following formula (I).
Formula (I) Si (OR 1 ) 4
[In the formula (I), R 1 represents a linear or branched alkyl group having 1 to 4 carbon atoms. ]
The silicon alkoxide used for the coating is preferably a silicon alkoxide represented by the following formula (II).
Formula (II) (R 2 O) 3 Si-R 3 -Si (OR 4) 3
[In formula (II), R 2 and R 4 represent a linear or branched alkyl group having 1 to 4 carbon atoms, and R 3 represents a linear or branched divalent group having 1 to 10 carbon atoms. It represents a saturated hydrocarbon group or an unsaturated hydrocarbon group, or an arylene group or heteroarylene group having 6 to 30 carbon atoms, which may have a substituent. ]
又は、被覆に使用される珪素アルコキシドとしては、上記の式（Ｉ）及び下記の式（ＩＩＩ）で表される珪素アルコキシドの混合物であることが好ましい。
式（ＩＩＩ） Ｒ5Ｓｉ（ＯＲ6）3
［式（ＩＩＩ）中、Ｒ5は炭素原子数１〜８の直鎖状若しくは分岐状のアルキル基、又は
置換基を有していてもよい炭素原子数６〜３０のアリール基を表し、Ｒ6は炭素原子数１
〜４の直鎖又は分岐のアルキル基を表す。］
Alternatively, the silicon alkoxide used for coating is preferably a mixture of silicon alkoxides represented by the above formula (I) and the following formula (III).
Formula (III) R 5 Si (OR 6 ) 3
[In formula (III), R 5 represents a linear or branched alkyl group having 1 to 8 carbon atoms, or an aryl group having 6 to 30 carbon atoms which may have a substituent, and R 6 is 1 carbon atom
-4 linear or branched alkyl groups are represented. ]
本発明に使用される珪素アルコキシドの具体例としては、テトラメトキシシラン、テトラエトキシシラン、テトラプロポキシシラン、テトラブトキシシラン等を挙げることができ、中でもテトラエトキシシランを用いることが好ましい。 Specific examples of the silicon alkoxide used in the present invention include tetramethoxysilane, tetraethoxysilane, tetrapropoxysilane, tetrabutoxysilane and the like. Among them, tetraethoxysilane is preferably used.
前記無孔質シリカによる被覆工程において、例えば１００〜１５０ｎｍの大きさのコア粒子の外周部を効率的、かつ確実に開孔部を被覆するには、被覆層の厚さによって変動するが、珪素アルコキシドは分散液中のメソ孔を有するコア粒子のＳｉＯ2成分に対してＳ
ｉＯ2換算で３０〜１００ｍｏｌ％加えられる。また、この際の反応温度は２０〜９０℃
であり、好ましくは２５〜６０℃である。また、この際の反応時間は１〜４８時間であり、好ましくは６〜２４時間である。本発明によれば、被覆工程において珪素アルコキシドの添加量及び反応条件を制御することで、内部のメソ孔を保持したまま、コア粒子の外周部を無孔質シリカによって被覆できる。
In the coating step with the nonporous silica, for example, the outer peripheral portion of the core particle having a size of 100 to 150 nm can be efficiently and surely covered with the aperture portion, although it varies depending on the thickness of the coating layer. The alkoxide is S against the SiO 2 component of the core particles having mesopores in the dispersion.
It added 30～100Mol% by iO 2 terms. Moreover, the reaction temperature in this case is 20-90 degreeC.
Preferably, it is 25-60 degreeC. Moreover, the reaction time in this case is 1-48 hours, Preferably it is 6-24 hours. According to the present invention, by controlling the amount of silicon alkoxide added and the reaction conditions in the coating step, the outer periphery of the core particles can be coated with nonporous silica while retaining the internal mesopores.
本発明のメソポーラスシリカ粒子分散液は、粒子外周部が３〜３０ｎｍの厚さの無孔質シリカで被覆され、３０〜３００ｎｍの一次粒子径を有し、且つ粒子内に２〜１０ｎｍのメソ孔を有するメソポーラスシリカ粒子が分散媒に分散されたものである。分散媒としては、水、アルコール類、ケトン類、エステル類、エーテル類、炭化水素類、ハロゲン化炭化水素類及びカルボン酸アミド類等が挙げられる。 The mesoporous silica particle dispersion of the present invention has a particle outer peripheral portion coated with nonporous silica having a thickness of 3 to 30 nm, a primary particle diameter of 30 to 300 nm, and 2 to 10 nm mesopores in the particles. Are mesoporous silica particles dispersed in a dispersion medium. Examples of the dispersion medium include water, alcohols, ketones, esters, ethers, hydrocarbons, halogenated hydrocarbons, and carboxylic acid amides.
前記アルコール類としては、メタノール、エタノール、１−プロパノール、２−プロパノール、１−ブタノール、イソブチルアルコール、２−ブタノール、エチレングリコール、グリセリン、プリピレングリコール、トリエチレングリコール、ポリエチレングリコール、ベンジルアルコール、１，５−ペンタンジオール及びジアセトンアルコール等が挙げられる。 Examples of the alcohols include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, isobutyl alcohol, 2-butanol, ethylene glycol, glycerin, propylene glycol, triethylene glycol, polyethylene glycol, benzyl alcohol, 1, Examples include 5-pentanediol and diacetone alcohol.
前記ケトン類としては、メチルエチルケトン（ＭＥＫ）、ジエチルケトン、メチルイソブチルケトン（ＭＩＢＫ）、メチルアミルケトン及びシクロヘキサノン等が挙げられる。 Examples of the ketones include methyl ethyl ketone (MEK), diethyl ketone, methyl isobutyl ketone (MIBK), methyl amyl ketone, and cyclohexanone.
前記エステル類としては、酢酸エチル、酢酸ブチル、プロピレングリコールメチルエーテルアセテート、ジエチレングリコールモノエチルエーテルアセテート、アクリル酸メチル及びメタクリル酸メチル等が挙げられる。 Examples of the esters include ethyl acetate, butyl acetate, propylene glycol methyl ether acetate, diethylene glycol monoethyl ether acetate, methyl acrylate and methyl methacrylate.
前記エーテル類としては、ジエチルエーテル、ジブチルエーテル、テトラヒドロフラン、ジオキサン、エチレングリコールモノメチルエーテル、エチレングリコールモノプロピルエーテル、プロピレングリコールモノメチルエーテル、プロピレングリコールモノエチルエーテル、ジエチレングリコールモノメチルエーテル、ジエチレングリコールモノエチルエーテル及びジエチレングリコールモノブチルエーテル等が挙げられる。 Examples of the ethers include diethyl ether, dibutyl ether, tetrahydrofuran, dioxane, ethylene glycol monomethyl ether, ethylene glycol monopropyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, and diethylene glycol monobutyl ether. Etc.
前記炭化水素類としては、ｎ−ヘキサン、シクロヘキサン、トルエン、キシレン及びソルベントナフサ等が挙げられる。 Examples of the hydrocarbons include n-hexane, cyclohexane, toluene, xylene, and solvent naphtha.
前記ハロゲン化炭化水素類としては、四塩化炭素、ジクロロエタン及びクロロベンゼン等が挙げられる。 Examples of the halogenated hydrocarbons include carbon tetrachloride, dichloroethane, and chlorobenzene.
前記カルボン酸アミドとしては、ジメチルホルムアミド（ＤＭＦ）、ジメチルアセトアミド及びＮ−メチルピロリドン等が挙げられる。 Examples of the carboxylic acid amide include dimethylformamide (DMF), dimethylacetamide, and N-methylpyrrolidone.
また、分散媒としては、重合性モノマーを挙げることができる。重合性モノマーとしては、例えば、アクリル酸、メタクリル酸、イタコン酸、クロトン酸、マレイン酸及びフタル酸等の不飽和カルボン酸化合物が挙げられる。また、これらの不飽和カルボン酸化合物とアルコール化合物若しくはアミン化合物とから誘導される不飽和カルボン酸エステル化合物又は不飽和カルボン酸アミド化合物を挙げることができる。例えば、アクリル酸エステル化合物、メタクリル酸エステル化合物、フタル酸アミド化合物等である。より具体的には、エチレングリコールジ（メタ）アクリレート、ジエチレングリコールジ（メタ）アクリレート、トリエチレングリコールジ（メタ）アクリレート等である。 Examples of the dispersion medium include polymerizable monomers. Examples of the polymerizable monomer include unsaturated carboxylic acid compounds such as acrylic acid, methacrylic acid, itaconic acid, crotonic acid, maleic acid, and phthalic acid. Moreover, the unsaturated carboxylic acid ester compound or unsaturated carboxylic acid amide compound induced | guided | derived from these unsaturated carboxylic acid compounds, an alcohol compound, or an amine compound can be mentioned. For example, acrylic acid ester compounds, methacrylic acid ester compounds, phthalic acid amide compounds, and the like. More specifically, ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate and the like.
また、重合性モノマーとしてはエポキシ環を有する重合性化合物を使用することができる。エポキシ環を有する重合性化合物は、例えばジオール化合物、トリオール化合物、ジカルボン酸化合物、トリカルボン酸化合物等の２個以上のヒドロキシ基又はカルボキシル基を有する化合物と、エピクロルヒドリン等のグリシジル化合物から製造することができる、２個以上のグリシジルエーテル構造又はグリシジルエステル構造を有する化合物を挙げることができる。 Moreover, the polymeric compound which has an epoxy ring can be used as a polymerizable monomer. The polymerizable compound having an epoxy ring can be produced from a compound having two or more hydroxy groups or carboxyl groups such as a diol compound, a triol compound, a dicarboxylic acid compound and a tricarboxylic acid compound, and a glycidyl compound such as epichlorohydrin. Examples thereof include compounds having two or more glycidyl ether structures or glycidyl ester structures.
エポキシ環を有する重合性化合物の具体例としては、１，４−ブタンジオールジグリシジルエーテル、１，２−エポキシ−４−（エポキシエチル）シクロヘキサン、グリセロールトリグリシジルエーテル、ジエチレングリコールジグリシジルエーテル及び２，６−ジグリシジルフェニルグリシジルエーテル等が挙げられる。 Specific examples of the polymerizable compound having an epoxy ring include 1,4-butanediol diglycidyl ether, 1,2-epoxy-4- (epoxyethyl) cyclohexane, glycerol triglycidyl ether, diethylene glycol diglycidyl ether, and 2,6. -Diglycidyl phenyl glycidyl ether etc. are mentioned.
この他、オキセタン環を有する重合性化合物として、３−エチル−３−ヒドロキシメチルオキセタン、３−エチル−３−（フェノキシメチル）オキセタン等、ビニルエーテル構造を有する重合性化合物として、ビニル−２−クロロエチルエーテル、ビニル−ノルマルブチルエーテル、１，４−シクロヘキサンジメタノールジビニルエーテル、ビニルグリシジルエーテル等を挙げることができる。 In addition, as a polymerizable compound having an oxetane ring, 3-ethyl-3-hydroxymethyloxetane, 3-ethyl-3- (phenoxymethyl) oxetane, or the like, a polymerizable compound having a vinyl ether structure, such as vinyl-2-chloroethyl Examples include ether, vinyl-normal butyl ether, 1,4-cyclohexanedimethanol divinyl ether, vinyl glycidyl ether, and the like.
本発明のメソポーラスシリカ粒子分散液の固形分濃度は、ＳｉＯ2として０．０１〜３
０質量％であり、０．１質量％以上であることが好ましい。
The solid content of the mesoporous silica particle dispersion of the present invention, as SiO 2 0.01 to 3
It is 0 mass%, and it is preferable that it is 0.1 mass% or more.
また本発明は、次の（Ａ）工程、（Ｃ）工程及び（Ｄ）工程を含む粒子外周部が３〜３０ｎｍの厚さの無孔質シリカで被覆され、３０〜３００ｎｍの一次粒子径を有し、且つ粒子内に２〜１０ｎｍのメソ孔を有する、機能性物質担持メソポーラスシリカ粒子分散液の製造方法である。
（Ａ）工程：界面活性剤及びｐＨ調整剤を含む水溶液にシリカ源（ａ）を添加して粒子内に２〜１０ｎｍのメソ孔を有するシリカ粒子の分散液を作製した後、界面活性剤を除去する工程、
（Ｃ）工程：前記（Ａ）工程で得られたメソ孔を有するシリカ粒子の分散液に有機化合物又はポリマーを加えて、当該メソ孔の少なくとも一部に有機化合物又はポリマーが充填した複合シリカ粒子の分散液を作製する工程、並びに
（Ｄ）工程：前記（Ｃ）工程で得られた複合シリカ粒子の分散液にｐＨ調整剤を加えてｐＨ８〜１０に調整した後、シリカ源（ｂ）を加え、撹拌下で２０〜９０℃、１〜４８時間処理して複合シリカ粒子の外周部を３〜３０ｎｍの厚さの無孔質シリカで被覆する工程。
Further, in the present invention, the outer periphery of the particle including the following steps (A), (C) and (D) is coated with nonporous silica having a thickness of 3 to 30 nm, and the primary particle diameter of 30 to 300 nm is increased. And a functional substance-supported mesoporous silica particle dispersion having 2-10 nm mesopores in the particles.
Step (A): A silica source (a) is added to an aqueous solution containing a surfactant and a pH adjuster to prepare a dispersion of silica particles having 2 to 10 nm mesopores in the particles, and then the surfactant is added. Removing,
Step (C): Composite silica particles in which an organic compound or polymer is added to the dispersion of silica particles having mesopores obtained in step (A), and at least part of the mesopores is filled with the organic compound or polymer. And (D) step: adjusting the pH to 8 to 10 by adding a pH adjusting agent to the dispersion of the composite silica particles obtained in the step (C), and then adding the silica source (b). In addition, a step of coating the outer peripheral portion of the composite silica particles with nonporous silica having a thickness of 3 to 30 nm by treating at 20 to 90 ° C. for 1 to 48 hours under stirring.
メソ孔内に充填される有機化合物又はポリマーとしては、２〜１０ｎｍのメソ孔に充填可能なものであれば特に制限はなく、色素導入によるバイオイメージングの観点から紫外線、及び可視光に吸収を持つ化合物、例えばベンゼン、ビフェニル、ターフェニル、クァテルフェニル、ベンゾフェノン、フルオレン、アントラキノン、ナフタレン、アセナフテン、カルバゾール、トリフェニレン、フェナントレン、アクリジン、アクリドン、アズレン、クリセン、ピレン、アントラセン、ペリレン、ビアセチル、ベンジル、フルオレセイン、エオシン、ローダミンＢ、及びこれらの誘導体を挙げることができる。ポリマーとしては、タンパク質、核酸、脂質等の生体高分子、ポリ塩化ビニル、ポリエチレン、ポリプロピレン、フェノール樹脂等の合成高分子などを挙げることができる。 The organic compound or polymer filled in the mesopores is not particularly limited as long as it can fill the mesopores of 2 to 10 nm, and has absorption in ultraviolet rays and visible light from the viewpoint of bioimaging by introducing a dye. Compounds such as benzene, biphenyl, terphenyl, quaterphenyl, benzophenone, fluorene, anthraquinone, naphthalene, acenaphthene, carbazole, triphenylene, phenanthrene, acridine, acridone, azulene, chrysene, pyrene, anthracene, perylene, biacetyl, benzyl, fluorescein, Mention may be made of eosin, rhodamine B and derivatives thereof. Examples of the polymer include biopolymers such as proteins, nucleic acids, and lipids, and synthetic polymers such as polyvinyl chloride, polyethylene, polypropylene, and phenol resins.
以下、実施例を挙げて、本発明をより具体的に説明するが、本発明は下記の実施例に限定されるものではない。 EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated more concretely, this invention is not limited to the following Example.
物性測定には以下の装置を使用した。
・ＢＥＴ測定装置：Quantachrome Instruments Autosorb-1
・窒素吸脱測定装置：Quantachrome Instruments Autosorb-1
・透過型電子顕微鏡（ＴＥＭ）：日本電子JEM-2010
・動的光散乱法粒子径測定装置：HORIBA Nano Partica SZ-100-S
The following apparatus was used for the physical property measurement.
・ BET measuring device: Quantachrome Instruments Autosorb-1
・ Nitrogen adsorption / desorption measurement system: Quantachrome Instruments Autosorb-1
・ Transmission electron microscope (TEM): JEOL JEM-2010
-Dynamic light scattering particle size measuring device: HORIBA Nano Partica SZ-100-S
〔実施例１〕
（コア粒子分散液の作製）
鋳型となる界面活性剤として、セチルトリメチルアンモニウムブロミド５．５ｍｍｏｌを含む水溶液２４０ｍＬ中にテトラプロポキシシランを０．０１１ｍｏｌ添加し、撹拌下にて８０℃、１２時間保持してメソポーラスシリカ粒子（ｉ）分散液を合成した。
[Example 1]
(Preparation of core particle dispersion)
As a template surfactant, 0.011 mol of tetrapropoxysilane was added to 240 mL of an aqueous solution containing 5.5 mmol of cetyltrimethylammonium bromide, and kept at 80 ° C. for 12 hours with stirring to disperse mesoporous silica particles (i). A liquid was synthesized.
メソポーラスシリカ粒子（ｉ）分散液５０ｍＬを透析膜（日本メディカルサイエンス社製 ヴィスキングチューブ（セルロース製））を有する装置に入れ、酢酸：エタノール＝
１：１（体積比）の混合溶媒２５０ｍＬ中で２５℃、２４時間、撹拌下で保持してセチルトリメチルアンモニウムブロミドを抽出した。同様の操作を５回繰り返した後、純水２５０ｍＬ中で２５℃、２４時間、撹拌下で保持する操作を４回繰り返して、メソポーラスシリカ粒子（ｉｉ）分散液を合成した。この分散液の動的光散乱法（ＤＬＳ）で測定されるメソポーラスシリカ粒子の分散粒子径は１４８ｎｍであった。上記のメソポーラスシリカ粒子（ｉｉ）分散液を乾燥して得られたメソポーラスシリカ粒子（ｉｉ）のＢＥＴ比表面積は約７４０ｍ2／ｇ、ＢＪＨ法により算出した細孔径は平均３．２ｎｍであり、細孔容
積は１．７ｍｌ／ｇであった。また、透過型電子顕微鏡（ＴＥＭ）観察から測定したメソポーラスシリカ粒子（ｉｉ）の１次粒子径は１４０ｎｍであった。透析によって界面活性剤が除去されたことは、ＣＨＮ分析（Perkin-Elmer 2400 Series II）によって確認した
。
50 mL of the mesoporous silica particle (i) dispersion is put in a device having a dialysis membrane (Visking tube (manufactured by cellulose) manufactured by Nippon Medical Science Co., Ltd.), and acetic acid: ethanol =
Cetyltrimethylammonium bromide was extracted by maintaining the mixture in 250 mL of 1: 1 (volume ratio) mixed solvent at 25 ° C. for 24 hours with stirring. The same operation was repeated 5 times, and then the operation of holding the mixture under stirring in 250 mL of pure water at 25 ° C. for 24 hours was repeated 4 times to synthesize a mesoporous silica particle (ii) dispersion. The dispersion particle diameter of the mesoporous silica particles measured by the dynamic light scattering method (DLS) of this dispersion was 148 nm. The mesoporous silica particles (ii) obtained by drying the above mesoporous silica particles (ii) have a BET specific surface area of about 740 m 2 / g and an average pore diameter calculated by the BJH method of 3.2 nm. The pore volume was 1.7 ml / g. The primary particle diameter of the mesoporous silica particles (ii) measured from observation with a transmission electron microscope (TEM) was 140 nm. The removal of the surfactant by dialysis was confirmed by CHN analysis (Perkin-Elmer 2400 Series II).
（粒子外周部の被覆）
メソポーラスシリカ粒子（ｉｉ）分散液２４０ｍＬにトリエタノールアミンを添加してｐＨ８．８に調整した後、テトラエトキシシラン４．４ｍｍｏｌ加え、６０℃、１２時間、撹拌下で保持して粒子外周部が無孔質シリカで被覆されたメソポーラスシリカ粒子（ｉｉｉ）を合成した。この時、外周部の無孔質シリカ量はメソ孔を有するシリカ粒子のＳｉＯ2量に対して４０ｍｏｌ％であった。得られたメソポーラスシリカ粒子（ｉｉｉ）のＢ
ＥＴ比表面積は約１２０ｍ2／ｇであり、窒素原子が充填可能なメソ孔は存在しなかった
。また、透過型電子顕微鏡（ＴＥＭ）観察から測定したシリカ粒子の１次粒子径は１５０ｎｍであり、新たなシリカ粒子の形成は見られなかった。この分散液の動的光散乱法によって測定される分散粒子径は１６０ｎｍであった。
(Coating of particle periphery)
After adding triethanolamine to 240 mL of the mesoporous silica particle (ii) dispersion to adjust the pH to 8.8, 4.4 mmol of tetraethoxysilane was added, and the mixture was held at 60 ° C. for 12 hours with stirring, so that the outer periphery of the particle was not present. Mesoporous silica particles (iii) coated with porous silica were synthesized. At this time, the amount of nonporous silica in the outer peripheral portion was 40 mol% with respect to the amount of SiO 2 in the silica particles having mesopores. B of the obtained mesoporous silica particles (iii)
The ET specific surface area was about 120 m 2 / g, and there were no mesopores that could be filled with nitrogen atoms. Moreover, the primary particle diameter of the silica particle measured from transmission electron microscope (TEM) observation was 150 nm, and formation of a new silica particle was not seen. The dispersion particle diameter measured by the dynamic light scattering method of this dispersion was 160 nm.
〔実施例２〕
実施例１で得られたメソポーラスシリカ粒子（ｉｉ）分散液５ｍＬをローダミンＢ０．１ｇを含む水溶液３０ｍＬ中に添加して得られた複合シリカ粒子の分散液を、実施例１に記載のシリカ粒子外周部の被覆方法と同様に処理して、内部にメソ孔を有する複合シリカ粒子（ｉｖ）分散液を合成した。この分散液を実施例１に記載の透析操作と同様に処理したところ、ローダミンＢ由来の赤色が残存しており、ローダミンＢがシリカ粒子内に封入されていることを確認した。
[Example 2]
The dispersion of composite silica particles obtained by adding 5 mL of the mesoporous silica particle (ii) dispersion obtained in Example 1 to 30 mL of an aqueous solution containing 0.1 g of rhodamine B was used as the outer periphery of the silica particles described in Example 1. The composite silica particle (iv) dispersion having mesopores inside was synthesized by the same treatment as the coating method for the part. When this dispersion was treated in the same manner as the dialysis operation described in Example 1, the red color derived from rhodamine B remained, and it was confirmed that rhodamine B was enclosed in the silica particles.
〔比較例〕
実施例１の粒子外周部の被覆方法において、テトラエトキシシランの添加量を２．２ｍｍｏｌに減らした結果、ＤＬＳで測定した粒径は１４４ｎｍ、ＴＥＭで測定した粒径は１４３ｎｍとなった。この時、外周部の無孔質シリカ量はメソ孔を有するシリカ粒子のＳｉＯ2量に対して２０ｍｏｌ％であった。また、ＢＥＴ比表面積は３８０ｍ2／ｇであり、メソ孔への窒素分子の吸着が見られたことから、閉塞が不完全であることが確認できた。
[Comparative Example]
In the coating method of the outer peripheral portion of the particle of Example 1, the amount of tetraethoxysilane added was reduced to 2.2 mmol. As a result, the particle size measured by DLS was 144 nm, and the particle size measured by TEM was 143 nm. At this time, the amount of nonporous silica in the outer peripheral portion was 20 mol% with respect to the amount of SiO 2 of the silica particles having mesopores. Further, the BET specific surface area was 380 m 2 / g, and adsorption of nitrogen molecules into the mesopores was observed, so that it was confirmed that the blockage was incomplete.
本発明のメソポーラスシリカ粒子は、その高い表面積、大きな細孔容積（粒子内部の空隙）を活用して、薬剤のキャリアとしてドラッグデリバリーや、色素導入によるバイオイメージングなどの医療材料への応用に適している。また、樹脂と複合化することによる低反射率（Ｌｏｗ−ｎ）、低誘電率（Ｌｏｗ−ｋ)、低熱伝導率材料などへ応用することが
できる。
The mesoporous silica particles of the present invention are suitable for application to medical materials such as drug delivery as a drug carrier and bioimaging by introducing a dye by utilizing their high surface area and large pore volume (voids inside the particles). Yes. Further, it can be applied to a low reflectivity (Low-n), low dielectric constant (Low-k), low thermal conductivity material, etc. by compounding with resin.
Claims (7)
前記（Ａ）工程で得られたメソ孔を有するシリカ粒子の分散液にｐＨ調整剤を加えてｐＨ８〜１０に調整した後、シリカ源（ｂ）を加え、撹拌下で２０〜９０℃、１〜４８時間処理してメソ孔を有するシリカ粒子の外周部を３〜３０ｎｍの厚さの無孔質シリカで被覆する（Ｂ）工程
を含む、請求項２に記載のメソポーラスシリカ粒子分散液の製造方法。 A silica source (a) is added to an aqueous solution containing a surfactant and a pH adjuster to prepare a dispersion of silica particles having 2 to 10 nm mesopores in the particles, and then the surfactant is removed (A). Step, and after adjusting the pH to 8 to 10 by adding a pH adjuster to the dispersion of silica particles having mesopores obtained in the step (A), the silica source (b) is added, and 20 to 90 under stirring. The mesoporous silica particle dispersion according to claim 2, comprising a step (B) of coating the outer peripheral portion of silica particles having mesopores at a temperature of 1 to 48 hours at 3 ° C with nonporous silica having a thickness of 3 to 30 nm. Liquid manufacturing method.
式（Ｉ） Ｓｉ（ＯＲ1）4
［式（Ｉ）中、Ｒ1は炭素原子数１〜４の直鎖又は分岐のアルキル基を表す。］ The method for producing a mesoporous silica particle dispersion according to claim 3, wherein the silica source (a) and the silica source (b) are silicon alkoxides represented by the formula (I).
Formula (I) Si (OR 1 ) 4
[In the formula (I), R 1 represents a linear or branched alkyl group having 1 to 4 carbon atoms. ]
式（ＩＩ） （Ｒ2Ｏ）3Ｓｉ−Ｒ3−Ｓｉ（ＯＲ4）3
［式（ＩＩ）中、Ｒ2及びＲ4は炭素原子数１〜４の直鎖又は分岐のアルキル基を表し、Ｒ3は炭素原子数１〜１０の直鎖状若しくは分岐状の２価の飽和炭化水素基若しくは不飽和
炭化水素基、又は置換基を有していてもよい、炭素原子数６〜３０のアリーレン基若しくはヘテロアリーレン基を表す。］
式（Ｉ） Ｓｉ（ＯＲ1）4
［式（Ｉ）中、Ｒ1は炭素原子数１〜４の直鎖又は分岐のアルキル基を表す。］
式（ＩＩＩ） Ｒ5Ｓｉ（ＯＲ6）3
［式（ＩＩＩ）中、Ｒ5は炭素原子数１〜８の直鎖状若しくは分岐状のアルキル基、又は
置換基を有していてもよい炭素原子数６〜３０のアリール基を表し、Ｒ6は炭素原子数１
〜４の直鎖又は分岐のアルキル基を表す。］ The silica source (a) and the silica source (b) are silicon alkoxides represented by the formula (II) or a mixture of silicon alkoxides represented by the formulas (I) and (III). A method for producing the mesoporous silica particle dispersion described above.
Formula (II) (R 2 O) 3 Si-R 3 -Si (OR 4) 3
[In formula (II), R 2 and R 4 represent a linear or branched alkyl group having 1 to 4 carbon atoms, and R 3 represents a linear or branched divalent group having 1 to 10 carbon atoms. It represents a saturated hydrocarbon group or an unsaturated hydrocarbon group, or an arylene group or heteroarylene group having 6 to 30 carbon atoms, which may have a substituent. ]
Formula (I) Si (OR 1 ) 4
[In the formula (I), R 1 represents a linear or branched alkyl group having 1 to 4 carbon atoms. ]
Formula (III) R 5 Si (OR 6 ) 3
[In formula (III), R 5 represents a linear or branched alkyl group having 1 to 8 carbon atoms, or an aryl group having 6 to 30 carbon atoms which may have a substituent, and R 6 is 1 carbon atom
-4 linear or branched alkyl groups are represented. ]
前記（Ａ）工程で得られたメソ孔を有するシリカ粒子の分散液に有機化合物又はポリマーを加えて、当該メソ孔の少なくとも一部に有機化合物又はポリマーが充填した複合シリカ粒子の分散液を作製する（Ｃ）工程、並びに
前記（Ｃ）工程で得られた複合シリカ粒子の分散液にｐＨ調整剤を加えてｐＨ８〜１０に調整した後、シリカ源（ｂ）を加え、撹拌下で２０〜９０℃、１〜４８時間処理して複合シリカ粒子の外周部を３〜３０ｎｍの厚さの無孔質シリカで被覆する（Ｄ）工程
を含む、粒子外周部が３〜３０ｎｍの厚さの無孔質シリカで被覆され、３０〜３００ｎｍの一次粒子径を有し、且つ粒子内に２〜１０ｎｍのメソ孔を有する、機能性物質担持メソポーラスシリカ粒子分散液の製造方法。 A silica source (a) is added to an aqueous solution containing a surfactant and a pH adjuster to prepare a dispersion of silica particles having 2 to 10 nm mesopores in the particles, and then the surfactant is removed (A). Process,
An organic compound or polymer is added to the dispersion of silica particles having mesopores obtained in the step (A) to produce a dispersion of composite silica particles in which at least a part of the mesopores is filled with the organic compound or polymer. Step (C), and after adjusting the pH to 8 to 10 by adding a pH adjuster to the dispersion of composite silica particles obtained in Step (C), the silica source (b) is added and 20 to 20 with stirring. Including the step (D) of treating the outer peripheral portion of the composite silica particles with nonporous silica having a thickness of 3 to 30 nm by treating at 90 ° C. for 1 to 48 hours, the outer peripheral portion of the particles has a thickness of 3 to 30 nm. A method for producing a functional substance-supported mesoporous silica particle dispersion, which is coated with porous silica, has a primary particle size of 30 to 300 nm, and has 2 to 10 nm mesopores in the particles.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2014168496A JP6357051B2 (en) | 2014-08-21 | 2014-08-21 | Mesoporous silica particles coated with nonporous silica and method for producing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2014168496A JP6357051B2 (en) | 2014-08-21 | 2014-08-21 | Mesoporous silica particles coated with nonporous silica and method for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2016044091A true JP2016044091A (en) | 2016-04-04 |
| JP6357051B2 JP6357051B2 (en) | 2018-07-11 |
Family
ID=55634984
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014168496A Active JP6357051B2 (en) | 2014-08-21 | 2014-08-21 | Mesoporous silica particles coated with nonporous silica and method for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6357051B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018212275A1 (en) * | 2017-05-19 | 2018-11-22 | 株式会社トクヤマ | Pharmaceutical ingredient carrier and method for producing same |
| JP6557443B1 (en) * | 2018-04-06 | 2019-08-07 | 株式会社アドマテックス | Filler for resin composition, slurry composition containing filler, filler-containing resin composition, and method for producing filler for resin composition |
| WO2019193766A1 (en) * | 2018-04-06 | 2019-10-10 | 株式会社アドマテックス | Filler for resin composition, filler-containing slurry composition, filler-containing resin composition, and method for producing filler for resin composition |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109589418B (en) * | 2018-12-14 | 2020-08-18 | 华南理工大学 | Schiff base copolymer coated mesoporous silica drug-loaded nanoparticle with pH responsiveness and preparation method and application thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07133105A (en) * | 1993-11-04 | 1995-05-23 | Catalysts & Chem Ind Co Ltd | Multiple oxide sol, its production and base material |
| JP2002173319A (en) * | 2000-12-05 | 2002-06-21 | Asahi Kasei Corp | Mesoporous material |
| JP2009196829A (en) * | 2008-02-19 | 2009-09-03 | Furukawa Electric Co Ltd:The | Method for producing silica nanoparticles of core-shell structure, silica nanoparticles of core-shell structure and labeling reagent using the same |
| JP2012171833A (en) * | 2011-02-21 | 2012-09-10 | Panasonic Corp | Mesoporous silica particles, method for producing mesoporous silica particles, and mesoporous silica particle-containing molded article |
| JP2012524014A (en) * | 2009-04-15 | 2012-10-11 | コーネル ユニバーシティ | Fluorescent silica nanoparticles improved by densification of silica |
| WO2014024379A1 (en) * | 2012-08-10 | 2014-02-13 | パナソニック株式会社 | Mesoporous silica fine particles, method for producing mesoporous silica fine particles, mesoporous silica fine particle-containing composition, mesoporous silica fine particle-containing molding, and organic electroluminescence element |
-
2014
- 2014-08-21 JP JP2014168496A patent/JP6357051B2/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07133105A (en) * | 1993-11-04 | 1995-05-23 | Catalysts & Chem Ind Co Ltd | Multiple oxide sol, its production and base material |
| JP2002173319A (en) * | 2000-12-05 | 2002-06-21 | Asahi Kasei Corp | Mesoporous material |
| JP2009196829A (en) * | 2008-02-19 | 2009-09-03 | Furukawa Electric Co Ltd:The | Method for producing silica nanoparticles of core-shell structure, silica nanoparticles of core-shell structure and labeling reagent using the same |
| JP2012524014A (en) * | 2009-04-15 | 2012-10-11 | コーネル ユニバーシティ | Fluorescent silica nanoparticles improved by densification of silica |
| JP2012171833A (en) * | 2011-02-21 | 2012-09-10 | Panasonic Corp | Mesoporous silica particles, method for producing mesoporous silica particles, and mesoporous silica particle-containing molded article |
| WO2014024379A1 (en) * | 2012-08-10 | 2014-02-13 | パナソニック株式会社 | Mesoporous silica fine particles, method for producing mesoporous silica fine particles, mesoporous silica fine particle-containing composition, mesoporous silica fine particle-containing molding, and organic electroluminescence element |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018212275A1 (en) * | 2017-05-19 | 2018-11-22 | 株式会社トクヤマ | Pharmaceutical ingredient carrier and method for producing same |
| JPWO2018212275A1 (en) * | 2017-05-19 | 2020-03-19 | 株式会社トクヤマ | Drug substance carrier and method for producing the same |
| US11246931B2 (en) | 2017-05-19 | 2022-02-15 | Tokuyama Corporation | Active pharmaceutical ingredient carrier and production method of the same |
| JP7200097B2 (en) | 2017-05-19 | 2023-01-06 | 株式会社トクヤマ | Active pharmaceutical ingredient carrier and method for producing the same |
| JP6557443B1 (en) * | 2018-04-06 | 2019-08-07 | 株式会社アドマテックス | Filler for resin composition, slurry composition containing filler, filler-containing resin composition, and method for producing filler for resin composition |
| WO2019193766A1 (en) * | 2018-04-06 | 2019-10-10 | 株式会社アドマテックス | Filler for resin composition, filler-containing slurry composition, filler-containing resin composition, and method for producing filler for resin composition |
| WO2019194321A1 (en) * | 2018-04-06 | 2019-10-10 | 株式会社アドマテックス | Filler for resin composition, filler-containing slurry composition, filler-containing resin composition, and method for producing filler for resin composition |
| US11091647B2 (en) | 2018-04-06 | 2021-08-17 | Admatechs., Ltd. | Filler for resinous composition, filler-containing slurry composition and filler-containing resinous composition as well as production process for filler for resinous composition |
Also Published As
| Publication number | Publication date |
|---|---|
| JP6357051B2 (en) | 2018-07-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wan et al. | A magnetic‐field guided interface coassembly approach to magnetic mesoporous silica nanochains for osteoclast‐targeted inhibition and heterogeneous nanocatalysis | |
| JP5827735B2 (en) | Method for producing porous silica | |
| JP6357051B2 (en) | Mesoporous silica particles coated with nonporous silica and method for producing the same | |
| Liu et al. | Preparation of porous hollow SiO 2 spheres by a modified Stöber process using MF microspheres as templates | |
| TW200844164A (en) | Cellulose fine particle, dispersion liquid thereof and dispersion body thereof | |
| JP5274809B2 (en) | Manufacturing method of low dielectric constant film | |
| TWI757680B (en) | A kind of composite microsphere with radial fibrous mesoporous shell layer/hollow core layer structure and preparation method thereof | |
| TW201226451A (en) | Hollow organic silane microspheres having rough surface structures and the method for the preparation thereof | |
| Bayat et al. | Electrospun chitosan/polyvinyl alcohol nanocomposite holding polyaniline/silica hybrid nanostructures: An efficient adsorbent of dye from aqueous solutions | |
| Fard et al. | Preparation of nano-cellulose/Α-Fe2O3 hybrid nanofiber for the cationic dyes removal: Optimization characterization, kinetic, isotherm and error analysis | |
| Uddin Ahmad et al. | Adsorptive removal of resorcinol onto surface modified ordered mesoporous carbon: kinetics and equilibrium study | |
| Cong et al. | Fabrication of monodisperse anisotropic silica hollow microspheres using polymeric cave particles as templates | |
| Huang et al. | Enantioselective absorption of enantiomers with maleic anhydride-β-cyclodextrin modified magnetic microspheres | |
| CN104226275A (en) | Hollow microsphere based on methacrylic acyloxy cage-like silsesquioxane and preparation method and application thereof | |
| Li et al. | A novel silica‐based nucleating agent for polypropylene: Preparation, characterization, and application | |
| Xing et al. | Polymerizable molecular silsesquioxane cage armored hybrid microcapsules with in situ shell functionalization | |
| Mohammadnezhad et al. | High Surface Area Nano‐Boehmite as Effective Nano‐Filler for Preparation of Boehmite‐Polyamide‐6 Nanocomposites | |
| CN104212297A (en) | Preparation method of styrene-grafted hollow silicon dioxide super-hydrophobic film | |
| CN106731871A (en) | The method that inorganic particulate induction phase separation prepares super-hydrophobic mixed substrate membrane containing nano-grade molecular sieve | |
| He et al. | Cagelike polymer microspheres with hollow core/porous shell structures | |
| KR20120056337A (en) | Method for Preparing Hollow Silica Particle | |
| CN105236427B (en) | A kind of nanoscale ordered mesoporous silica dioxide ball and preparation method thereof | |
| JP2007246795A (en) | Process for production of porous silica coating film and coating liquid for powder (including powder precursor) formation | |
| Mu et al. | Facile preparation of crosslinked polymeric nanocapsules via combination of surface-initiated atom transfer radical polymerization and ultraviolet irradiated crosslinking techniques | |
| Yan et al. | Aggregation‐Induced Emission Gemini Surfactant‐Assisted Fabrication of Shape‐Controlled Fluorescent Hollow Mesoporous Silica Nanoparticles |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20170511 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20171124 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20171206 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180130 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20180606 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180615 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6357051 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |