JP5594670B2 - Method for producing coated composite material using liquid-liquid interface - Google Patents
Method for producing coated composite material using liquid-liquid interface Download PDFInfo
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- JP5594670B2 JP5594670B2 JP2010549516A JP2010549516A JP5594670B2 JP 5594670 B2 JP5594670 B2 JP 5594670B2 JP 2010549516 A JP2010549516 A JP 2010549516A JP 2010549516 A JP2010549516 A JP 2010549516A JP 5594670 B2 JP5594670 B2 JP 5594670B2
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D9/00—Crystallisation
- B01D9/005—Selection of auxiliary, e.g. for control of crystallisation nuclei, of crystal growth, of adherence to walls; Arrangements for introduction thereof
- B01D9/0054—Use of anti-solvent
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
- B01J2/006—Coating of the granules without description of the process or the device by which the granules are obtained
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
- B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
- B01J2/06—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops in a liquid medium
Description
本発明は、被覆型複合物質を製造する方法に関する。 The present invention relates to a method for producing a coated composite material.
医薬品、化粧品など様々な分野で利用される粉体を使った材料の特性は、粉体の形状、粒子径および粒子径分布によって非常に大きな影響を受ける。そのため、材料に所望の機能を発揮させるためには、個々の粒子の形態を精緻に制御することが重要となってくる。 The characteristics of materials using powders used in various fields such as pharmaceuticals and cosmetics are greatly influenced by the shape, particle size and particle size distribution of the powder. Therefore, in order for the material to exhibit a desired function, it is important to precisely control the morphology of individual particles.
粒子生成方法のなかでも晶析法は、目的の特性を持った結晶を再現性よく製造できる技術として注目されており、これまでにも研究がなされてきた。この晶析法は、過飽和状態で起こる核発生や結晶成長を利用して気相や液相から結晶を析出させる操作であり、粒子生成過程での形態制御が可能である。しかし、冷却法、蒸発法のような晶析法では、加熱、冷却操作により溶液内を過飽和状態にさせ結晶を得ることが一般的であり、熱エネルギーが必要である。また系内の温度の制御は非常に困難であり、そのため粒子形態がばらつくといった問題がある。 Of the particle generation methods, the crystallization method has attracted attention as a technique capable of producing crystals having the desired characteristics with high reproducibility, and has been studied so far. This crystallization method is an operation for precipitating crystals from a gas phase or a liquid phase using nucleation or crystal growth that occurs in a supersaturated state, and can control the form during the particle generation process. However, in a crystallization method such as a cooling method and an evaporation method, it is common to obtain a crystal by supersaturating the solution by heating and cooling operations, and heat energy is required. In addition, it is very difficult to control the temperature in the system, and there is a problem that the particle morphology varies.
さらに貧溶媒法では、溶媒添加時に生成する局所的な高過飽和により、得られる結晶は様々な形状を有し粒子径がばらつくといった問題がある。
一方、本発明者は、各種物質の溶液から、特別な加熱や冷却手段を使用しなくとも、簡単に表面積の大きな結晶を得る方法として、液−液界面を利用する結晶析出方法を提案している（特許文献１参照）。Further, in the poor solvent method, there is a problem that the crystals obtained have various shapes and the particle diameters vary due to local high supersaturation generated when the solvent is added.
On the other hand, the present inventor has proposed a crystal precipitation method using a liquid-liquid interface as a method for easily obtaining a crystal having a large surface area from a solution of various substances without using special heating or cooling means. (See Patent Document 1).
前記液−液界面晶析法は、相互溶解する２溶媒Ａ、Ｂを接触させ、その液−液界面上で結晶を析出、成長させる晶析法である。結晶化物質は溶媒Ａにのみ溶解するものを選択する。このように２液を接触させると、相互溶解度曲線にしたがって溶液Ａ’の溶媒Ａが溶媒Ｂへ移動することで界面近傍では溶媒が減少し、同時に溶媒Ｂが溶媒Ａに溶解することで結晶化物質の溶解度が低下することから過飽和度が高くなり液―液界面上で結晶化物質を析出させ、成長させることができる。
この液−液界面晶析法によれば、従来の晶析法の操作とは異なり、結晶化に際し熱エネルギーを用いないため、常温・恒温で操作が可能である。また、結晶の析出場を界面に限定するため、系内の過飽和度が比較的均一になり、連続的に結晶を成長させることができるという利点を有する。The liquid-liquid interface crystallization method is a crystallization method in which two solvents A and B that are mutually dissolved are brought into contact with each other, and crystals are precipitated and grown on the liquid-liquid interface. A crystallizing substance that is soluble only in solvent A is selected. When the two liquids are brought into contact with each other in this manner, the solvent A in the solution A ′ moves to the solvent B according to the mutual solubility curve, so that the solvent is reduced in the vicinity of the interface, and at the same time, the solvent B is dissolved in the solvent A and crystallizes. Since the solubility of the substance decreases, the degree of supersaturation increases and the crystallized substance can be deposited and grown on the liquid-liquid interface.
According to this liquid-liquid interface crystallization method, unlike the operation of the conventional crystallization method, since heat energy is not used for crystallization, the operation can be performed at normal temperature and constant temperature. Further, since the crystal precipitation field is limited to the interface, the supersaturation degree in the system becomes relatively uniform, and there is an advantage that the crystal can be continuously grown.
しかし、特許文献１の方法では、２液の界面形状を制御することが難しいため、粒子形態の制御が難しく、また、析出した結晶の形態を保持して回収することが困難であった。 However, in the method of Patent Document 1, since it is difficult to control the interface shape of the two liquids, it is difficult to control the particle morphology, and it is difficult to retain and collect the precipitated crystal morphology.
したがって、本発明は、穏和な条件下および簡易な工程にて、物質の大きさや形態を制御できる方法を提供することを課題とする。 Therefore, an object of the present invention is to provide a method capable of controlling the size and form of a substance under mild conditions and in a simple process.
本発明者らは、前記課題を解決するために研究を重ねた結果、
溶質Ｓを溶媒Ａに高濃度に溶解してなる溶液Ａ’と、
前記溶媒Ａに対して親和性を有するが混和性が低く、且つ、前記溶質Ｓを実質的に溶解しない溶媒Ｂと、
前記溶媒Ａおよび溶媒Ｂのいずれにも溶解しない担体Ｃ
とを用意し、
前記担体Ｃの表面を溶液Ａ’で被覆した後、当該担体Ｃの被覆表面を溶媒Ｂと接触させることにより、前記担体Ｃの表面上に、前記溶質Ｓを晶析させることにより、前記課題を解決することに成功した。As a result of repeated studies to solve the above problems, the present inventors have
A solution A ′ obtained by dissolving the solute S in the solvent A at a high concentration;
A solvent B that has an affinity for the solvent A but has low miscibility and does not substantially dissolve the solute S;
Carrier C that does not dissolve in either solvent A or solvent B
And prepare
After the surface of the carrier C is coated with the solution A ′, the solute S is crystallized on the surface of the carrier C by bringing the coated surface of the carrier C into contact with the solvent B. Successfully solved.
本発明の方法によれば、担体Ｃの表面を溶液Ａ’で被覆した後、当該被覆表面を溶媒Ｂと接触させるため、担体Ｃの表面形状に沿って２液間の界面を形成することができる。そして、担体Ｃの表面に付着した溶液Ａ’の溶媒Ａが、溶媒Ｂに溶解するに伴って、溶質Ｓを析出させ、結晶として成長させ、その結果、前記担体Ｃの表面を、晶析した溶質Ｓにより被覆することができ、有用物質からなる表層を有する担体（被覆型複合体）を製造することができる。そのため、任意の形状およびサイズに作製した担体を用いることにより、単独では形態を制御しにくい物質であっても、任意の形状とサイズを持ち、表面が当該物質からなる複合体を得ることができる。
また当該方法は、物質のコーティング方法としても有用である。特に、当該方法は、常温で実施することができるため、熱に弱い物質であっても、担体上に晶析させて担体をコーティングすることができる。さらに、一般に、無機物質を有機物質でコーティングすることは難しいとされているが、本発明によれば、無機物質／有機物質からなる被覆型複合体であっても容易に製造することができる。According to the method of the present invention, after the surface of the carrier C is coated with the solution A ′, the interface between the two liquids can be formed along the surface shape of the carrier C in order to bring the coated surface into contact with the solvent B. it can. Then, as the solvent A of the solution A ′ adhering to the surface of the carrier C is dissolved in the solvent B, the solute S is precipitated and grown as crystals, and as a result, the surface of the carrier C is crystallized. A carrier (coated complex) that can be coated with the solute S and has a surface layer made of a useful substance can be produced. Therefore, by using a carrier prepared in an arbitrary shape and size, even if it is a substance whose form is difficult to control by itself, a complex having an arbitrary shape and size and having a surface made of the substance can be obtained. .
The method is also useful as a material coating method. In particular, since the method can be carried out at room temperature, even a substance that is weak against heat can be crystallized on the support to coat the support. Furthermore, although it is generally considered difficult to coat an inorganic substance with an organic substance, according to the present invention, even a coated composite made of an inorganic substance / organic substance can be easily manufactured.
また、前記溶液Ａ’で被覆された状態の前記担体Ｃを、前記溶媒Ｂに噴霧する方法によれば、当該担体Ｃの被覆表面全体を溶媒Ｂと効率よく接触させることができる。
特に、前記担体Ｃを分散させた溶液Ａ’を、前記溶媒Ｂに噴霧する方法が好ましい。この方法によれば、担体Ｃを溶液Ａ’に分散させることで、担体Ｃの表面を溶液Ａ’で効率よく濡らす（被覆する）ことができ、また、担体Ｃを溶液Ａ’ごと溶媒Ｂに噴霧すればよいため、操作が簡便である。この方法によれば、１００μｍ以下の微細な被覆型複合体であっても、効率よく製造することができる。Further, according to the method of spraying the carrier C coated with the solution A ′ onto the solvent B, the entire coated surface of the carrier C can be efficiently brought into contact with the solvent B.
In particular, a method in which the solution A ′ in which the carrier C is dispersed is sprayed onto the solvent B is preferable. According to this method, by dispersing the support C in the solution A ′, the surface of the support C can be efficiently wetted (coated) with the solution A ′, and the support C is added to the solvent B together with the solution A ′. Since spraying is sufficient, the operation is simple. According to this method, even a fine coated composite of 100 μm or less can be efficiently produced.
また、前記溶質Ｓが結晶多形を有する物質である場合、準安定形および／または不安定形の結晶形として晶析させることが可能である。物質が結晶多形を有する場合、結晶形によって、結晶の融点や溶解度のような物理的・化学的性質は異なるため、多形転移を制御することは非常に重要となる。本発明によれば、結晶多形を有する物質を、不安定形もしくは準安定形として晶析させることが可能である。 In addition, when the solute S is a substance having a crystal polymorph, it can be crystallized as a metastable and / or unstable crystal form. When a substance has a crystalline polymorph, physical and chemical properties such as the melting point and solubility of the crystal differ depending on the crystalline form, so it is very important to control the polymorphic transition. According to the present invention, it is possible to crystallize a substance having a crystalline polymorph as an unstable or metastable form.
本発明によれば、簡単な工程および穏和な条件により、非常に微細な担体（平均粒子径100μｍ以下）であっても、その表面を被覆することができる。したがって、単独では形態を制御しにくい物質であっても、担体の形態を制御することにより、任意の大きさや形状を有し、表層が当該物質からなる複合体を製造することができる。また、本発明によれば、従来、複雑な工程や特殊な製造条件が必要とされていた、微細物質のコーティングや有機物による無機物のコーティングであっても、容易に実施することができる。 According to the present invention, the surface of even a very fine carrier (average particle size of 100 μm or less) can be coated by a simple process and mild conditions. Therefore, even if it is a substance whose form is difficult to control by itself, by controlling the form of the carrier, it is possible to produce a complex having an arbitrary size and shape and whose surface layer is made of the substance. Further, according to the present invention, it is possible to easily carry out coating of a fine substance or an inorganic substance with an organic substance, which has conventionally required complicated processes and special manufacturing conditions.
本発明で使用される溶質Ｓは無機物質であっても有機物質であってもよい。有機物質の例として、グリシンやタウリンといったアミノ酸を挙げることができる。無機物質の例として、塩化ナトリウム、塩化カリウム、リン酸二水素カリウムを挙げることができる。なお、例示した上記溶質と組み合わせて使用する溶媒としては、溶媒Ａとして水、溶媒Ｂとして１−ブタノール、イソブチルアルコール、２−ブタノン等が好適である。 The solute S used in the present invention may be an inorganic substance or an organic substance. Examples of organic substances include amino acids such as glycine and taurine. Examples of inorganic substances include sodium chloride, potassium chloride, and potassium dihydrogen phosphate. As the solvent used in combination with the exemplified solute, water as the solvent A and 1-butanol, isobutyl alcohol, 2-butanone and the like as the solvent B are preferable.
本発明にかかる溶媒Ｂは、溶媒Ａと親和性があるが、溶媒Ａと混和性が低い溶媒である必要がある。
溶媒Ａと親和性がある溶媒とは、常温で溶媒Ａにわずかでも溶解する溶媒を意味する。すなわち、溶媒Ａに対する溶解度が1〜2wt%程度の溶媒でもよい。より好ましくは溶媒Ａに対する溶解度が4.0wt%以上の溶媒を用いる。
溶媒Ａと混和性が低いとは、溶媒Ａと溶媒Ｂの互いへの溶解度が36wt％以下であることを意味する。
このように溶媒Ａおよび溶媒Ｂとして、わずかに相互溶解するが本質的には混ざり合わない２液を用いることにより、被覆時に安定な液−液界面を形成することができ、均一な被覆が可能になる。
より具体的には、溶媒Ａおよび溶媒Ｂとして、互いへの溶解度が2wt％〜36wt％程度の２溶媒を用いることが好ましく、溶解度が7wt％〜34wt％程度の２溶媒を用いることがさらに好ましく、溶解度が7.8wt%〜20wt％程度の２溶媒を用いることが特に好ましい。このような２溶媒の例として、水と１−ブタノール、水とイソブチルアルコール、水と２−ブタノン等の組合せが挙げられる。
また、溶媒Ｂについて、溶質Ｓを実質的に溶解しないとは、溶質の溶解度が8.6×10-2 mol/kg未満であることを意味する。The solvent B according to the present invention has an affinity for the solvent A, but needs to be a solvent having low miscibility with the solvent A.
The solvent having an affinity for the solvent A means a solvent that dissolves even slightly in the solvent A at room temperature. That is, a solvent having a solubility in the solvent A of about 1 to 2 wt% may be used. More preferably, a solvent having a solubility in the solvent A of 4.0 wt% or more is used.
Low miscibility with solvent A means that the solubility of solvent A and solvent B in each other is 36 wt% or less.
In this way, a stable liquid-liquid interface can be formed at the time of coating by using two liquids slightly soluble in each other but essentially not mixed as solvent A and solvent B, and uniform coating is possible. become.
More specifically, as the solvent A and the solvent B, it is preferable to use two solvents having a solubility of about 2 wt% to 36 wt%, and more preferably using two solvents having a solubility of about 7 wt% to 34 wt%. It is particularly preferable to use two solvents having a solubility of about 7.8 wt% to 20 wt%. Examples of such two solvents include combinations of water and 1-butanol, water and isobutyl alcohol, water and 2-butanone, and the like.
Further, regarding the solvent B, the fact that the solute S is not substantially dissolved means that the solubility of the solute is less than 8.6 × 10 −2 mol / kg.
本発明で使用される担体Ｃは無機物質であっても有機物質であってもよい。粒子形態の制御を目的とする場合、所望の形態に制御しやすい物質が好ましく、例としてシリカ（SiO2）、アルミナ（Al2O3），ゼオライト等を挙げることができる。コーティングを目的とする場合は、所望の物質を担体に用いて当該方法を行うことができる。例えば、酸化鉄をコーティングして磁性複合粒子とし、細胞分離や診断用のキャリアに応用する、あるいは酸化チタンをコーティングして複合粒子とし、光触媒、顔料、紫外線防止材等へ応用する、あるいはフェライト（Fe2O3）を有機物でコーティングし、核磁気共鳴診断（MRI）用の造影剤として応用する、などを目的とする場合は、それぞれ酸化鉄、酸化チタン、フェライトを担体として用いればよい。The carrier C used in the present invention may be an inorganic substance or an organic substance. For the purpose of controlling the particle form, a substance that can be easily controlled to a desired form is preferable, and examples thereof include silica (SiO 2 ), alumina (Al 2 O 3 ), zeolite, and the like. When coating is intended, the method can be performed using a desired substance as a carrier. For example, iron oxide is coated into magnetic composite particles and applied to cell separation and diagnostic carriers, or titanium oxide is coated into composite particles and applied to photocatalysts, pigments, UV protection materials, etc., or ferrite ( For the purpose of coating Fe 2 O 3 ) with an organic substance and applying it as a contrast agent for nuclear magnetic resonance diagnosis (MRI), iron oxide, titanium oxide, and ferrite may be used as a carrier, respectively.
本発明の溶液Ａ’において、溶質Ｓを高濃度に溶解したとは、飽和濃度の75％以上の溶質が溶解されていることを意味する。飽和濃度の90％〜100％の溶質が溶解されていることが好ましく、また、過飽和であってもよい。
以下、実施例により本発明をさらに詳細に説明するが、本発明はこれらの実施例に限定されるものではない。In the solution A ′ of the present invention, the dissolution of the solute S at a high concentration means that a solute having a saturation concentration of 75% or more is dissolved. It is preferable that 90% to 100% of the solute at the saturation concentration is dissolved, and it may be supersaturated.
EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these Examples.
溶質Ｓとしてグリシンを、溶媒Ａとして水を、溶媒Ｂとして１−ブタノール（以下単にブタノールと称する）を、担体Ｃとしてシリカ（SiO2）粒子を用いて実験を行った。また、図１Ａに示す実験装置を使用した。
グリシン（溶質Ｓ）を水（溶媒Ａ）に溶解してグリシン飽和水溶液（3.463mol/L：溶液Ａ’）を調製した。この飽和水溶液に平均粒子径72.5μmのシリカ粒子（担体Ｃ）を10重量％（水溶液中のグリシン質量の10重量％：以下同じ）添加し、スターラーで撹拌して（撹拌条件300rpm）、シリカ粒子の全表面がグリシン飽和水溶液で濡れる（被覆される）ようにした。次に、このシリカ粒子を含むグリシン飽和水溶液（担体Ｃを分散状態で含む溶液Ａ’）を図１Ａに示すようにセットし、液体ローラポンプで吸い取り、ブタノール（溶媒Ｂ）200mlが入ったビーカーに、上部から噴霧した。図中に示すドラフターには、ノズルが設置されており、ノズルの先端で気体と液体を衝突させることによって微細な液滴を作製することができる。ノズルは、二流体（気体１＋液体１）以上を流出させることにより、液滴を作製できるものであればよい。本実施例では、図１Ｂに示すように、円錐状にスリットが入っておりその円錐に沿って気体と液体が流れて先端で衝突するノズル（ペンシルノズル）を用いた。気体は図に示すエアコンプレッサーを通じ、ガス流量計によって流出速度を調節してノズルの内管に供給される。
本実施例では、気体の流出速度を20L/min、液体（担体Ｃを含む溶液Ａ’）の流出速度を8ml/minに設定し、5秒間噴霧し、60秒間静置した後、ろ過装置によって固液分離を行った。Experiments were conducted using glycine as the solute S, water as the solvent A, 1-butanol (hereinafter simply referred to as butanol) as the solvent B, and silica (SiO 2 ) particles as the carrier C. Moreover, the experimental apparatus shown in FIG. 1A was used.
Glycine (solute S) was dissolved in water (solvent A) to prepare a saturated aqueous glycine solution (3.463 mol / L: solution A ′). To this saturated aqueous solution, 10% by weight of silica particles (carrier C) having an average particle diameter of 72.5 μm (10% by weight of the glycine mass in the aqueous solution: the same shall apply hereinafter) is added and stirred with a stirrer (stirring conditions: 300 rpm). The entire surface of the substrate was wetted (coated) with a saturated aqueous glycine solution. Next, a saturated aqueous glycine solution containing silica particles (solution A ′ containing carrier C in a dispersed state) is set as shown in FIG. 1A, sucked with a liquid roller pump, and placed in a beaker containing 200 ml of butanol (solvent B). Sprayed from the top. The drafter shown in the figure is provided with a nozzle, and fine droplets can be produced by causing a gas and a liquid to collide at the tip of the nozzle. The nozzle may be any nozzle that can produce droplets by causing two fluids (gas 1 + liquid 1) or more to flow out. In this embodiment, as shown in FIG. 1B, a nozzle (pencil nozzle) that has a conical slit and gas and liquid flow along the cone and collides at the tip is used. The gas is supplied to the inner pipe of the nozzle through an air compressor shown in the figure, with the outflow rate adjusted by a gas flow meter.
In this embodiment, the gas outflow rate is set to 20 L / min, the liquid (solution A ′ containing the carrier C) outflow rate is set to 8 ml / min, sprayed for 5 seconds, allowed to stand for 60 seconds, and then filtered. Solid-liquid separation was performed.
図２に、固液分離によって採取した固体の走査型電子顕微鏡（SEM）写真を示す。写真から、グリシンで被覆されたシリカ粒子の存在が確認できた。 In FIG. 2, the scanning electron microscope (SEM) photograph of the solid extract | collected by solid-liquid separation is shown. From the photograph, the presence of silica particles coated with glycine was confirmed.
実施例１により、グリシン−シリカ複合粒子の作製が可能であることが分かったが、破損して当初の球形を保持していないシリカ粒子が散見された。複合物質の形態制御のためには、シリカ粒子の形態を保つことが重要であるため改良を試みた。考察の結果、シリカ粒子の破損は、水溶液を撹拌する際のスターラーにより生じた可能性があるため、撹拌方法をスターラーから波動式シェーカーに変更して実験を行った。波動式シェーカーにより、約傾斜角5°，100rpmで30分間撹拌を行った以外は、実施例１と同じ条件により実験を行った。
さらに、シリカ粒子を30重量％（水溶液中のグリシン質量の30重量％：以下同じ）添加した場合についても、同様に実験を行った。According to Example 1, it was found that glycine-silica composite particles could be produced, but there were some silica particles that were broken and did not retain the original spherical shape. In order to control the form of the composite material, it was important to maintain the form of the silica particles, so an improvement was attempted. As a result of consideration, since the silica particles may be damaged by a stirrer when stirring the aqueous solution, the stirring method was changed from a stirrer to a wave-type shaker, and an experiment was conducted. The experiment was performed under the same conditions as in Example 1 except that the stirring was carried out for 30 minutes with a wave shaker at an inclination angle of about 5 ° and 100 rpm.
Further, the same experiment was performed when 30% by weight of silica particles (30% by weight of glycine in the aqueous solution: the same applies hereinafter) was added.
図３に、固液分離によって採取した固体のSEM写真を示す。グリシンで被覆されたシリカ粒子の存在が確認できるとともに、シリカ粒子の破損が減少し、シリカ粒子の当初の形態を保有した球形被覆型複合粒子を多く作製することができることが分かった。またシリカの量が変化しても同じように被覆型複合粒子の作製ができることが分かった。 In FIG. 3, the SEM photograph of the solid extract | collected by solid-liquid separation is shown. It was found that the presence of silica particles coated with glycine could be confirmed, and the damage of the silica particles was reduced, so that many spherical coated composite particles having the original form of the silica particles could be produced. It was also found that coated composite particles can be produced in the same manner even if the amount of silica changes.
噴霧条件が複合粒子の作製に与える影響を調べるため、ノズルに供給する溶液Ａ’（シリカ粒子含有グリシン飽和水溶液）の液体流出速度を2、4、6、8、10ml/minと変化させて実験を行った。シリカ粒子の添加量は30重量％とした。その他の条件は、実施例２と同一である。 In order to investigate the effect of spraying conditions on the production of composite particles, experiment was conducted by changing the liquid flow rate of solution A ′ (saturated glycine solution containing silica particles) supplied to the nozzle to 2, 4, 6, 8, 10 ml / min. Went. The amount of silica particles added was 30% by weight. Other conditions are the same as those in the second embodiment.
図４に、各液体流出速度にて得られたシリカ粒子のSEM写真を示す。どの水溶液流速においても、グリシンで被覆された球形のシリカ粒子の存在が確認された。 FIG. 4 shows SEM photographs of silica particles obtained at each liquid outflow rate. The presence of spherical silica particles coated with glycine was confirmed at any aqueous solution flow rate.
担体の粒子径を制御することにより、複合粒子の粒子径を制御することができるかを調べるために、担体（シリカ）の平均粒子径を5.71μm、30.9μmの二種類に変更して実験を行った。シリカの添加量は10重量％で行なった。その他の実験条件は実施例２と同一である。なお、シリカ粒子の平均粒子径は、SEMによって測定した際の画像解析により算出したMartin粒子径である。 In order to investigate whether the particle size of the composite particles can be controlled by controlling the particle size of the carrier, the average particle size of the carrier (silica) was changed to two types of 5.71 μm and 30.9 μm. went. The amount of silica added was 10% by weight. Other experimental conditions are the same as in Example 2. The average particle size of the silica particles is the Martin particle size calculated by image analysis when measured by SEM.
平均粒子径5.71μmのシリカを用いた際に得られた粒子のSEM写真を図５に示す。SEM写真から、グリシンはシリカ表面上で結晶化せず複合粒子が作製できていないことが分かった。また、粒子径分布を調べたところ、粒子径分布はシフトしていなかった。シリカの添加量を30重量％に変えて実験を行っても同じ結果が得られた。この原因は、生成したグリシン結晶に対してシリカ粒子が小さいため、グリシン結晶がシリカ上に存在するには不安定であったためと考えられる。SEM写真からも、グリシンはシリカ表面上に結晶化せずに個々に存在していることが分かる。 FIG. 5 shows an SEM photograph of particles obtained when silica having an average particle diameter of 5.71 μm is used. SEM photographs showed that glycine did not crystallize on the silica surface and composite particles could not be produced. Further, when the particle size distribution was examined, the particle size distribution was not shifted. The same result was obtained even when the experiment was performed with the addition amount of silica changed to 30% by weight. This is presumably because the silica particles were smaller than the glycine crystals produced, and the glycine crystals were unstable when present on the silica. SEM photographs also show that glycine exists individually on the silica surface without crystallizing.
平均粒子径30.9μmのシリカを用いた際に得られた粒子のSEM写真と粒子径分布を図６に示す。SEM写真から、グリシンはシリカ表面に結晶化していることが分かる。また、粒子径分布は粒子径が大きい方向に約5μmほどシフトしていた。これらのことから平均粒子径30.9μmのシリカでは膜厚約2.5μmの複合粒子が作製できたことが分かった。
なお、平均粒子径30.9μmのシリカについて、添加量を30重量％とし、且つ、ノズルに供給するシリカ粒子含有グリシン飽和水溶液の液体流出速度を2、4、6、8、10ml/minで変化させて実験を行ったが、いずれの場合も被覆型複合粒子を作製することができた。FIG. 6 shows an SEM photograph and particle size distribution of particles obtained when silica having an average particle size of 30.9 μm is used. The SEM photograph shows that glycine is crystallized on the silica surface. Further, the particle size distribution was shifted by about 5 μm in the direction of increasing the particle size. From these facts, it was found that composite particles having a film thickness of about 2.5 μm could be produced with silica having an average particle diameter of 30.9 μm.
For silica with an average particle size of 30.9 μm, the addition amount was 30% by weight, and the liquid outflow rate of the saturated aqueous glycine solution containing silica particles to be supplied to the nozzle was changed at 2, 4, 6, 8, 10 ml / min. In all cases, it was possible to produce coated composite particles.
本実施例から、析出させる溶質に対し、ある程度以上の大きさを持つ担体（好ましくは、析出した溶質結晶の平均径に対し10倍程度以上の平均径を持つ担体）を用いたほうが、担体表面に溶質を析出させやすいと考えられる。しかし、ある程度以上の大きさがあれば、担体の大きさを変えることにより、作製する複合粒子の大きさを制御することができることが分かった。通常、平均粒子径20μm以上の担体であれば、十分被覆化できると考えられる。 From this example, it is better to use a support having a certain size or more with respect to the solute to be precipitated (preferably, a support having an average diameter of about 10 times or more the average diameter of the precipitated solute crystals). It is thought that the solute is likely to be precipitated in However, it has been found that the size of the composite particles to be produced can be controlled by changing the size of the carrier if the size exceeds a certain level. Usually, it is considered that a carrier having an average particle diameter of 20 μm or more can be sufficiently coated.
水溶液濃度が複合粒子に及ぼす影響を調べるため、未飽和の6種の濃度のグリシン水溶液（0.866、1.299、1.731、2.164、2.597、3.030mol/L）を用いて実験を行った。シリカ（平均粒子径72.5μm）の添加量は各水溶液中のグリシン質量に対して30重量％とした。その他の実験条件は実施例２と同一である。 In order to investigate the influence of the aqueous solution concentration on the composite particles, experiments were conducted using 6 types of unsaturated glycine aqueous solutions (0.866, 1.299, 1.731, 2.164, 2.597, 3.030 mol / L). The amount of silica (average particle size 72.5 μm) added was 30% by weight with respect to the mass of glycine in each aqueous solution. Other experimental conditions are the same as in Example 2.
図７に、それぞれの濃度で作成した複合粒子のSEM写真を示す。図７から、グリシン濃度が上昇するにつれて、担体であるシリカが、結晶化したグリシンにより徐々に被覆されていることが分かる。2.597mol/L以上の濃度では、シリカ表面がほぼ全面被覆されていた。 FIG. 7 shows SEM photographs of the composite particles prepared at the respective concentrations. From FIG. 7, it can be seen that as the glycine concentration increases, the silica as a carrier is gradually covered with crystallized glycine. At a concentration of 2.597 mol / L or more, the silica surface was almost entirely covered.
さらに、平均粒子径30.9μmのシリカについて、未飽和の2種の濃度のグリシン水溶液（1.731、2.597mol/L）を用いて、複合粒子を作製した。シリカ添加量は10重量％とした。その他の実験条件は実施例２と同一である。
複合化の程度をSEM写真により観察した結果、1.731mol/Lでは複合化面積（被覆面積）が少なく、2.597mol/Lではシリカ表面がほぼ全面被覆されていることが分かった。Furthermore, composite particles were prepared using two unsaturated glycine aqueous solutions (1.731, 2.597 mol / L) for silica having an average particle diameter of 30.9 μm. The amount of silica added was 10% by weight. Other experimental conditions are the same as in Example 2.
As a result of observing the degree of compounding by SEM photographs, it was found that the composite area (coating area) was small at 1.731 mol / L, and the silica surface was almost entirely coated at 2.597 mol / L.
本実施例から、グリシン結晶は0.866mol/Lの濃度からでも析出することが分かったが、担体表面を均一に覆うためには、飽和濃度の約75%（2.597mol/L）以上とすることが好ましいと考えられる。 From this example, it was found that glycine crystals were precipitated even at a concentration of 0.866 mol / L. However, in order to uniformly cover the support surface, the concentration should be about 75% (2.597 mol / L) or more of the saturation concentration. Is considered preferable.
本実施例では、シリカの表面に析出させたグリシンの結晶多形をＸ線回折（XRD）により測定した。グリシン結晶には３種類の多形（α、β、γ）が存在し、その熱力学的安定性はγ>α>βの順となっている。したがって、グリシンの室温における熱力学的安定性は、γ形は安定形、α形は準安定形、β形はα形より安定性の低い準安定形である。β形は室温でα形やγ形に転移しやすいが低湿度ではβ形に保たれ、またα形は数ヶ月の期間でγ形に転移することが知られている。市販されているグリシンは通常γ形の結晶形を有する。 In this example, the crystal polymorph of glycine deposited on the surface of silica was measured by X-ray diffraction (XRD). There are three types of polymorphs (α, β, γ) in glycine crystals, and their thermodynamic stability is in the order of γ> α> β. Accordingly, the thermodynamic stability of glycine at room temperature is that the γ form is a stable form, the α form is a metastable form, and the β form is a metastable form that is less stable than the α form. It is known that the β form easily changes to the α form and the γ form at room temperature, but is kept in the β form at low humidity, and the α form changes to the γ form in a period of several months. Commercially available glycine usually has a gamma crystalline form.
XRDの測定結果を図８に示す。溶媒に溶解する前のグリシン（試料）は最も安定なγ形のピークを示した（図８の一番上のデータ）。これに対し、飽和のグリシン水溶液を用いて、シリカの表面に析出させたグリシン結晶は、最も不安定なβ形のピークを示した（図８の一番下のデータ）。
さらに、ビーカーに入れたグリシン飽和水溶液（シリカ粒子なし）の液面に、ブタノールを静かに注いで、ブタノールとグリシン飽和水溶液を２層に保った状態で、両者の界面にグリシン結晶を析出させ、この結晶の多形をXRDで測定したところ、α形のピークを示した（図８の２段目のデータ）。The measurement result of XRD is shown in FIG. The glycine (sample) before dissolving in the solvent showed the most stable γ-form peak (the top data in FIG. 8). On the other hand, glycine crystals precipitated on the surface of silica using a saturated glycine aqueous solution showed the most unstable β-form peak (bottom data in FIG. 8).
Furthermore, while pouring butanol gently onto the liquid surface of the saturated aqueous glycine solution (without silica particles) placed in a beaker and keeping the butanol and saturated aqueous glycine solution in two layers, glycine crystals are precipitated at the interface between the two, When the polymorph of this crystal was measured by XRD, it showed an α-form peak (data on the second stage in FIG. 8).
本実施例により、シリカ表面に析出させたグリシン結晶は、溶解前の最も安定なγ形から、最も不安定なβ形に変化していることが分かった。また、平面の液−液界面で析出した結晶形はα形であることから、同じ液−液界面を利用した結晶析出法であっても、噴霧によりシリカ粒子表面に析出させた結晶と、平面上の二層間に析出させた結晶では結晶形が異なることが分かった。
また、溶解前のグリシン試料およびグリシン−シリカ複合粒子を示差走査熱量測定（DSC）で測定し、グラフからそれぞれの融点を読み取ると、溶解前のグリシン試料は242℃となり、噴霧実験により作製したグリシン−シリカ複合粒子では227.6℃となった。このことからも、グリシンの多形変化が確認された。According to this example, it was found that the glycine crystals deposited on the silica surface changed from the most stable γ form before dissolution to the most unstable β form. In addition, since the crystal form precipitated at the flat liquid-liquid interface is α-form, even if the crystal precipitation method using the same liquid-liquid interface is used, It was found that the crystals deposited between the upper two layers differed in crystal form.
In addition, when the glycine sample before dissolution and the glycine-silica composite particles were measured by differential scanning calorimetry (DSC) and the respective melting points were read from the graph, the glycine sample before dissolution was 242 ° C. -It became 227.6 degreeC in the silica composite particle. This also confirmed the glycine polymorphic change.
グリシン水溶液の濃度が、シリカ表面に析出するグリシンの結晶形に与える影響を調べた。それぞれの濃度におけるXRD測定結果を図９に示す。図の８つのデータは、上から順に、溶解前のグリシン試料、並びに、0.866mol/L、1.299mol/L、1.731mol/L、2.164mol/L、2.597mol/L、3.030mol/L、3.463mol/L（飽和状態）の溶液を用いてシリカ表面上に析出させたグリシン結晶のデータを示す。未飽和状態の6種類の水溶液を用いて析出させたグリシン結晶はα形のピークを強く示す。しかし、濃度が高くなるにつれてβ形の混在が確認された。飽和状態である3.463mol/Lではほぼβ形のピークを示しているので、グリシン水溶液を未飽和の状態にすることでα形グリシンが結晶化することが分かった。 The effect of the concentration of the glycine aqueous solution on the crystal form of glycine deposited on the silica surface was investigated. The XRD measurement results at each concentration are shown in FIG. The eight data in the figure are the glycine sample before dissolution, and 0.866 mol / L, 1.299 mol / L, 1.731 mol / L, 2.164 mol / L, 2.597 mol / L, 3.030 mol / L, 3.463 in order from the top. The data of the glycine crystal | crystallization precipitated on the silica surface using the solution of mol / L (saturated state) are shown. Glycine crystals precipitated using six types of unsaturated solutions show strong α-form peaks. However, as the concentration increased, a mixture of β forms was confirmed. In the saturated state of 3.463 mol / L, a β-form peak was shown, and it was found that α-glycine crystallized when the glycine aqueous solution was brought into an unsaturated state.
このことから、濃度を変化させるといった非常に簡単な操作で、シリカ表面に析出するグリシンの結晶形をコントロールできる可能性があることが分かった。 From this, it was found that the crystal form of glycine deposited on the silica surface could be controlled by a very simple operation such as changing the concentration.
担体Ｃとして、直径１cm、厚さ1.5mmの円形のシリカ膜を作製した。また、グリシン（溶質Ｓ）を水（溶媒Ａ）に溶解してグリシン飽和水溶液（溶液Ａ’）を調製した。
このグリシン飽和水溶液に前記シリカ膜を30秒間浸漬してシリカ膜の表面をグリシン飽和水溶液で濡らした（被覆した）後、当該シリカ膜をビーカー内のブタノール（溶媒Ｂ）中に静かに落下させて浸漬し、60秒間静置後、固液分離した。
このシリカ膜のSEM写真を確認したところ、シリカ膜（担体Ｃ）上にグリシン（溶質Ｓ）が析出しており、噴霧した場合と同様、被覆複合化されていることが確認できた。As the carrier C, a circular silica film having a diameter of 1 cm and a thickness of 1.5 mm was produced. Further, glycine (solute S) was dissolved in water (solvent A) to prepare a saturated glycine aqueous solution (solution A ′).
After immersing the silica film in this saturated aqueous glycine solution for 30 seconds to wet (coat) the surface of the silica film with the saturated aqueous glycine solution, the silica film was gently dropped into butanol (solvent B) in a beaker. It was immersed and allowed to stand for 60 seconds, followed by solid-liquid separation.
When an SEM photograph of this silica film was confirmed, it was confirmed that glycine (solute S) was deposited on the silica film (carrier C) and was coated and composited as in the case of spraying.
本実施例からも、担体の形態を変えることにより、任意の形態の被覆型複合物質を製造できることが確認できた。 Also from this example, it was confirmed that by changing the form of the carrier, a coated composite material of any form could be produced.
上記の各実施例から、本発明を用いれば、室温で、かつ短時間で均一な被膜を有する複合体が製造できることが実証された。 From each of the above examples, it was proved that a composite having a uniform film can be produced at room temperature in a short time by using the present invention.
Claims (7)
前記溶媒Ａに対する溶解度が２ｗｔ％〜３６ｗｔ％であり、且つ、前記溶質Ｓを実質的に溶解しない溶媒Ｂと、
前記溶媒Ａおよび溶媒Ｂのいずれにも溶解しない担体Ｃ
とを用意し、
前記担体Ｃの表面を溶液Ａ’で被覆した後、当該担体Ｃの被覆表面を溶媒Ｂと接触させることにより、前記担体Ｃの表面上に、前記溶質Ｓを晶析させることによって、
担体Ｃの形状を有し、且つ、表層が溶質Ｓからなる被覆型複合物質を製造する方法。A solution A ′ obtained by dissolving the solute S in the solvent A at a high concentration;
A solvent B having a solubility in the solvent A of 2 wt% to 36 wt% and substantially not dissolving the solute S;
Carrier C that does not dissolve in either solvent A or solvent B
And prepare
After the surface of the carrier C is coated with the solution A ′, the solute S is crystallized on the surface of the carrier C by bringing the coated surface of the carrier C into contact with the solvent B.
A method for producing a coated composite material having the shape of a carrier C and having a surface layer made of a solute S.
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| JP2010549516A JP5594670B2 (en) | 2009-02-06 | 2010-02-05 | Method for producing coated composite material using liquid-liquid interface |
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| JP2009025783 | 2009-02-06 | ||
| PCT/JP2010/051670 WO2010090275A1 (en) | 2009-02-06 | 2010-02-05 | Process for producing coated composite substance utilizing liquid-liquid interface |
| JP2010549516A JP5594670B2 (en) | 2009-02-06 | 2010-02-05 | Method for producing coated composite material using liquid-liquid interface |
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| JPWO2010090275A1 JPWO2010090275A1 (en) | 2012-08-09 |
| JP5594670B2 true JP5594670B2 (en) | 2014-09-24 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0717943A (en) * | 1993-07-02 | 1995-01-20 | Mitsui Toatsu Chem Inc | Production of taurine |
| JP2003001600A (en) * | 2001-04-18 | 2003-01-08 | Univ Tokyo | Carbon thin line and manufacture method thereof |
| JP2006281193A (en) * | 2005-03-08 | 2006-10-19 | Doshisha | Crystal precipitation method utilizing liquid-liquid interface and novel crystal |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0717943A (en) * | 1993-07-02 | 1995-01-20 | Mitsui Toatsu Chem Inc | Production of taurine |
| JP2003001600A (en) * | 2001-04-18 | 2003-01-08 | Univ Tokyo | Carbon thin line and manufacture method thereof |
| JP2006281193A (en) * | 2005-03-08 | 2006-10-19 | Doshisha | Crystal precipitation method utilizing liquid-liquid interface and novel crystal |
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| JPWO2010090275A1 (en) | 2012-08-09 |
| WO2010090275A1 (en) | 2010-08-12 |
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