WO1999019370A1 - Process for producing polymer particles with uniform particle size - Google Patents

Process for producing polymer particles with uniform particle size Download PDF

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Publication number
WO1999019370A1
WO1999019370A1 PCT/JP1998/004665 JP9804665W WO9919370A1 WO 1999019370 A1 WO1999019370 A1 WO 1999019370A1 JP 9804665 W JP9804665 W JP 9804665W WO 9919370 A1 WO9919370 A1 WO 9919370A1
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Prior art keywords
particle size
polymer
particles
uniform particle
polymer particles
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PCT/JP1998/004665
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French (fr)
Japanese (ja)
Inventor
Ken Hosoya
Kimihiro Yoshizako
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Amersham Pharmacia Biotech K.K.
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Publication of WO1999019370A1 publication Critical patent/WO1999019370A1/en

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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
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
    • B01J20/282—Porous sorbents
    • B01J20/285—Porous sorbents based on polymers
    • 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
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
    • B01J20/26—Synthetic macromolecular compounds
    • B01J20/261—Synthetic macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds

Definitions

  • the present invention relates to a method for producing homogeneous polymer particles using an SPG membrane emulsification method, and a filler for chromatography which contains the particles.
  • a polymer particle filler having a uniform particle size particularly a polymer particle filler having a uniform particle size, has advantages such as high column performance and reduced pressure loss at that time.
  • various methods for preparing a polymer filler having uniform particle size include emulsion polymerization, dispersion polymerization, soap-free emulsion polymerization, suspension polymerization, and two-stage swelling polymerization, which is a kind of seed polymerization. It is performed using.
  • the two-stage swelling polymerization method is considered to be excellent as a method for preparing a polymer filler having a high degree of crosslinking required for pressure resistance.
  • An object of the present invention is to provide a high-performance chromatographic uniform polymer particle that eliminates the disadvantages of the uniform particle size polymer particle produced by the two-step swelling polymerization method in view of the above situation. is there.
  • the present inventors have prepared uniform polymer particles using SPG (Shirasu Porous G 1 ass) membrane emulsification method, and packed them with chromatography, such as high-performance liquid chromatography. It has been found that the above-mentioned disadvantages can be solved by using it as an agent.
  • the present inventor has found that the use of polymer particles having a uniform particle size obtained by the SPG membrane emulsification method as a packing material for chromatography allows the chromatography to be performed at almost the limit. It was confirmed that the Raffy theoretical plate number was achieved.
  • the present invention has been completed based on these findings.
  • the present invention relates to a method for producing polymer particles having a uniform particle diameter, characterized by using an SPG membrane emulsification method.
  • the present invention relates to a filler for chromatography containing the polymer particles having a uniform particle diameter obtained by the production method.
  • FIG. 1 shows a separation chromatogram of alkylbenzene by HPLC using a particle of about 3 m prepared by an SPG membrane emulsification method as a separating agent.
  • FIG. 2 is a diagram showing the pore size distribution of polymer particles having a particle size of about 3 / m prepared by the two-step swelling polymerization method and the SPG membrane emulsification method.
  • FIG. 3 is a diagram showing the pore size distribution of polymer particles having a particle size of about 5 // prepared by the two-step swelling polymerization method and the SPG membrane emulsification method.
  • the SPG membrane emulsification method used in the present invention is a method characterized in that one liquid that is not mixed is pressurized and penetrates through a porous glass membrane to prepare particles having a uniform particle size in the other liquid. It is.
  • the SPG membrane emulsification method for example, S. Omi, K.Kat ami, A. Yamamoto, and M.Iso, J. Ap p 1. Polym.Sci., 51 (1994) 1-11.
  • the polymer particles having a uniform particle size according to the present invention are produced as follows.
  • a mixed solution of a monomer as a raw material of the polymer particles having a uniform particle diameter and a diluent is prepared, and one side of the porous glass film is filled with the mixed solution and pressurized.
  • an aqueous solution in which a stabilizer or the like is dissolved an emulsion composed of uniform particles can be obtained.
  • polymerization is performed by heating or the like, whereby polymer particles having a uniform particle size are prepared.
  • the method of the present invention can be applied to a porous polymer and a non-porous polymer, and a porous polymer particle having a uniform particle size and a uniform non-porous polymer particle can be obtained.
  • porous polymer particles having a uniform particle size or non-porous polymer particles having a uniform particle size according to the present invention can be used for various chromatographic methods such as high performance liquid chromatography (HPLC) and capillary electrochromatography (CEC). It can be used as a filler.
  • HPLC high performance liquid chromatography
  • CEC capillary electrochromatography
  • the particle size of the porous polymer particles having a uniform particle size or the non-porous polymer particles having a uniform particle size can be appropriately set according to the type of chromatography to be used, the type of the substance to be separated, and the like. Desirable particle size is usually from 2 ⁇ m to 300 ⁇ m, preferably from 2 ⁇ m to 20 ⁇ m, but is not limited to this range.
  • Styrene, divinylbenzene, ethylene diacrylate, ethylene dimethacrylate, methyl acrylate, methyl methacrylate, glycidyl acrylate, methacrylic acid Glycidyl, acrylamide, N, N'-methylenebisacrylamide and the like can be mentioned. These monomers can be used in any combination.
  • the polymer used for the uniform particle size polymer particles of the present invention includes polystyrene, polydivinylbenzene, and poly (styrene-divinylbenzene).
  • examples thereof include glycidyl acrylate-diethylene methacrylate), poly (glycidyl methacrylate diethylene methacrylate), and poly (acrylamide-N, N'-methylenebisacrylamide).
  • the CV value representing the distribution of the particle size may be about 10%, and particularly preferably 10% or less.
  • polymers used in the present invention include poly (styrene vinyl benzene), polyacrylic acid, polyacrylic ester, Remethacrylic acid type, polymethacrylic acid ester type, polyhydroxyquinacrylic acid type, polyhydroxyacrylic acid ester type, polyhydroxymethacrylic acid type, polyhydroxymethacrylic acid ester type, polyvinyl polycarboxylate type filler etc. Can be.
  • the SPG film emulsifier used for producing the porous polymer particles having a uniform particle size of the present invention is not particularly limited, and examples thereof include an MPG film emulsifier Micro Kit manufactured by Ise Chemical Industry Co., Ltd. Example
  • Styrene and divinylbenzene were used as monomers, and an MPG membrane emulsifier microkit manufactured by Ise Chemical Industry Co., Ltd. was used as a membrane emulsifier, and the particle diameter was about 5 // m and about 3 m.
  • the membrane was selected so as to obtain particles.
  • a filler having a similar size was also prepared by a conventional two-stage swelling polymerization method. In this case, polystyrene seed particles were used. After the obtained particles were washed by a conventional method, they were packed in a stainless steel power ram by a wet method, and their column performances were compared.
  • the size and distribution of the obtained particles are determined by the pore diameter and the distribution of the membrane. Therefore, the particle size distribution is generally wider than in the two-stage swelling polymerization method.
  • the filler prepared by the SPG membrane emulsification method has a slightly higher CV value, which indicates the degree of particle size distribution. I understand. As a result, it was confirmed that it could be sufficiently used as a packing material for chromatography such as HPLC because it does not contain microparticles that increase the pressure loss of the column.
  • each particle having a different preparation method was compared with an optical microscope. The CV value was 10% for particles obtained by the two-step swelling polymerization method, and 10 to 15% for particles obtained by the SPG film emulsification method. Optical microscopy It was confirmed with a microscope.
  • the stainless steel force ram was wet-filled, but a similar packing method could be used for both particles.
  • the pressure drop of the packed column showed almost no difference under reversed phase conditions as shown below.
  • Particle size of about 3 / m; 9.6MPa This indicates that the particles prepared by the SPG membrane emulsification method do not contain, as expected, the fine particles that are the main cause of pressure loss.
  • the number of theoretical plates was about 15,000 for a column packed with about 3 particles and about 8000 for a column packed with about 5 m particles. It was also shown that the particles prepared by the SPG membrane emulsification method exhibited column performance comparable to that of the particles prepared by the two-step swelling polymerization method, and the column stability was good. This is about 3 when the conversion theory step is raised (theoretically, the limit is 2), and it can be said that almost the limit performance is achieved.
  • the particles prepared by the SPG membrane emulsification method were compared with the particles prepared by the two-stage swelling polymerization method, where the stability of the column was extremely reduced due to the destruction of the particle sphere by the seed particles. Due to the perfect spherical shape, column performance was not impaired at all even for particles as small as 3 z / m or less.
  • Figure 1 shows the separation chromatogram of alkylbenzene by HP LC using particles of about 3 // m prepared by the SPG membrane emulsification method as a separating agent.
  • the alkylbenzene chromatogram shown in Fig. 1 has sharp peaks, Since no significant deformation was observed, this indicates that the column is excellent as an analytical column.
  • the pore size distribution of the particles was determined by size exclusion chromatography using tetrahydrofuran as a mobile phase.
  • the results are shown in FIGS. M r shown in the figure is the molecular weight of the polystyrene used as the solute, and E 1 uti0nvolume is the elution volume of the solute.
  • Figure 2 shows the pore size distribution of a polymer particle with a particle size of about 3 m prepared by both methods
  • Figure 3 shows the pore size distribution of a polymer particle with a particle size of about 5 / m prepared by both methods.
  • a significant difference was observed in the pore size distribution between the fillers prepared by both methods.
  • the two-stage swelling polymerization method when the seed particles, polystyrene, dissolve in the diluent or monomer, the dissolved polystyrene functions as a polymer diluent, resulting in a porous material having larger pores. Although it tends to give particles, it is considered that the large pores formed by the polymer diluent were reduced by the absence of the seed polymer in the SPG membrane emulsification method. This is also observed in a general suspension polymerization method that does not use seed particles.Therefore, in the SPG membrane emulsification method, it is necessary to prepare a filler having properties similar to those of the conventional suspension polymerization method. Can be. Industrial applicability
  • the preparation of porous polymer particles having a uniform particle size by the SPG membrane emulsification method has the following advantages, and can be one of the methods for the synthesis of polymer fillers for chromatography in the future.
  • the method of the present invention allows the preparation of highly hydrophilic particles by using a continuous phase as an oil phase.
  • particles of 3 / m or less can be prepared.

Abstract

A process for producing polymer particles with uniform particle size, characterized by employing the SPG emulsification technique. This process permits the production of a porous chromatographic packing comprising polymer particles with uniform particle size and capable of enhancing the column performance and reducing the pressure loss.

Description

明 細 書  Specification
粒子径均ーポリマー粒子の製造方法 技術分野  Particle size-Method for producing polymer particles
本発明は、 S PG膜乳化法を用いる粒子怪均一ポリマー粒子の製造方法および 当該粒子を含むクロマ卜グラフィ一用充填剤に関する。 背景技術  The present invention relates to a method for producing homogeneous polymer particles using an SPG membrane emulsification method, and a filler for chromatography which contains the particles. Background art
粒子径均一ポリマー粒子充填剤、 特に粒子径均一多孔性ポリマー粒子充填剤は 与えるカラム性能が高く、 かつその際の圧力損失が低減される等の利点を有して いる。 種々の粒子径均一ポリマー粒子充填剤の調製法としては、 従来、 乳化重合 法、 分散重合法、 ソープフリー乳化重合法、 懸濁重合法、 シード重合法の一種で ある二段階膨潤重合法等を用いて行われている。 中でも、 耐圧性に必要な高架橋 度のポリマー充填剤を調製する方法としては、 二段階膨潤重合法は優れていると 考えられている。  A polymer particle filler having a uniform particle size, particularly a polymer particle filler having a uniform particle size, has advantages such as high column performance and reduced pressure loss at that time. Conventionally, various methods for preparing a polymer filler having uniform particle size include emulsion polymerization, dispersion polymerization, soap-free emulsion polymerization, suspension polymerization, and two-stage swelling polymerization, which is a kind of seed polymerization. It is performed using. In particular, the two-stage swelling polymerization method is considered to be excellent as a method for preparing a polymer filler having a high degree of crosslinking required for pressure resistance.
しかしながら、 二段階膨潤重合法によれば容易に粒子径均一ポリマー粒子を得 ることが可能であるが、 一方で種粒子を用いる必然性からその化学的、 物理的影 響が粒子のクロマトグラフィー特性に与える悪影響が否めない欠点があった。 発明の開示  However, according to the two-step swelling polymerization method, it is possible to easily obtain polymer particles having a uniform particle size, but on the other hand, the necessity of using seed particles causes the chemical and physical influences on the chromatographic properties of the particles. There was a drawback that the adverse effect on it was undeniable. Disclosure of the invention
本発明の目的は、 上記のような現状に鑑み、 二段階膨潤重合法により製造され た粒子径均一ポリマー粒子の持つ欠点を取り除いた高性能のクロマトグラフィー 用粒子怪均一ポリマー粒子を提供することである。  An object of the present invention is to provide a high-performance chromatographic uniform polymer particle that eliminates the disadvantages of the uniform particle size polymer particle produced by the two-step swelling polymerization method in view of the above situation. is there.
本発明者は、 鋭意研究の結果、 SPG (Sh i r a s u Po r o u s G 1 a s s) 膜乳化法を用いて粒子怪均一ポリマー粒子を調製し、 これを高速液体ク ロマ卜グラフィ一等のクロマトグラフィ一の充填剤として用いることにより上記 欠点を解消できることを見いだした。  As a result of earnest research, the present inventors have prepared uniform polymer particles using SPG (Shirasu Porous G 1 ass) membrane emulsification method, and packed them with chromatography, such as high-performance liquid chromatography. It has been found that the above-mentioned disadvantages can be solved by using it as an agent.
さらに、 本発明者は、 S PG膜乳化法により得られた粒子径均一ポリマー粒子 をクロマトグラフィ一の充填剤として用いることにより、 ほぼ限界のクロマ卜グ ラフィー理論段数が達成されることを確認した。 Furthermore, the present inventor has found that the use of polymer particles having a uniform particle size obtained by the SPG membrane emulsification method as a packing material for chromatography allows the chromatography to be performed at almost the limit. It was confirmed that the Raffy theoretical plate number was achieved.
本発明はこれらの知見に基づいて完成したものである。  The present invention has been completed based on these findings.
すなわち本発明は、 S PG膜乳化法を用いることを特徴とする粒子径均一ポリ マー粒子の製造方法に関する。  That is, the present invention relates to a method for producing polymer particles having a uniform particle diameter, characterized by using an SPG membrane emulsification method.
また、 本発明は、 該製造方法によって得られた粒子径均一ポリマ一粒子を含む クロマ卜グラフィー用充填剤に関する。 図面の簡単な説明  Further, the present invention relates to a filler for chromatography containing the polymer particles having a uniform particle diameter obtained by the production method. BRIEF DESCRIPTION OF THE FIGURES
図 1は、 S PG膜乳化法で調製した約 3 mの粒子を分離剤として用いた HP L Cによるアルキルベンゼンの分離クロマトグラムを表す。  FIG. 1 shows a separation chromatogram of alkylbenzene by HPLC using a particle of about 3 m prepared by an SPG membrane emulsification method as a separating agent.
図 2は、 二段階膨潤重合法および S PG膜乳化法で調製した粒子怪約 3 / mの ポリマー粒子の細孔怪分布を表す図である。  FIG. 2 is a diagram showing the pore size distribution of polymer particles having a particle size of about 3 / m prepared by the two-step swelling polymerization method and the SPG membrane emulsification method.
図 3は、 二段階膨潤重合法および S PG膜乳化法で調製した粒子径約 5 // の ポリマー粒子の細孔径分布を表す図である。 発明を実施するための最良の形態  FIG. 3 is a diagram showing the pore size distribution of polymer particles having a particle size of about 5 // prepared by the two-step swelling polymerization method and the SPG membrane emulsification method. BEST MODE FOR CARRYING OUT THE INVENTION
本発明において用いる S PG膜乳化法とは、 混合しない一方の液体を加圧して 多孔質ガラス膜に透過することにより、 他方の液体中で粒子径均一粒子を調製す ることを特徴とする方法である。 なお、 S PG膜乳化法については、 例えば、 S. Om i , K. K a t am i, A. Yamamo t o, a n d M. I s o, J. Ap p 1. Po l ym. S c i. , 51 (1994) 1— 11に記載されている。 本発明の粒子径均一ポリマー粒子は次のようにして製造される。 粒子径均一ポ リマー粒子の原料となるモノマーと希釈剤等の混合溶液を調製し、 多孔質ガラス 膜の片側に先の混合溶液を満たして加圧する。 多孔質ガラス膜の反対側に安定剤 等を溶解した水溶液を満たしておくことで、 粒子怪均一粒子からなるエマルジョ ンが得られる。 その後加熱等により重合を行うことで、 粒子径均一ポリマー粒子 が調製される。 なお、 本発明方法は多孔性ポリマーにも無孔性ポリマーにも適用 することができ、 それぞれ粒子径均一多孔性ポリマー粒子および粒子怪均一無孔 性ポリマー粒子を得ることができる。 このようにして製造された本発明の粒子径均一多孔性ポリマー粒子あるいは粒 子径均一無孔性ポリマー粒子は、 高速液体クロマトダフィー （H P L C ) 、 キヤ ピラリー電気クロマトグラフィー （C E C ) 等種々のクロマトダフィーの充填剤 として使用することができる。 粒子径均一多孔性ポリマー粒子あるいは粒子径均 一無孔性ポリマー粒子の粒子怪は、 使用するクロマトグラフィーの種類、 分離す る対象となる物質の種類等に応じて適宜設定することができる。 望ましい粒子径 は、 通常は 2〃m〜3 0 0〃m, 好ましくは 2〃 m〜 2 0〃 mであるが、 この範 囲に限定されない。 The SPG membrane emulsification method used in the present invention is a method characterized in that one liquid that is not mixed is pressurized and penetrates through a porous glass membrane to prepare particles having a uniform particle size in the other liquid. It is. Incidentally, regarding the SPG membrane emulsification method, for example, S. Omi, K.Kat ami, A. Yamamoto, and M.Iso, J. Ap p 1. Polym.Sci., 51 (1994) 1-11. The polymer particles having a uniform particle size according to the present invention are produced as follows. A mixed solution of a monomer as a raw material of the polymer particles having a uniform particle diameter and a diluent is prepared, and one side of the porous glass film is filled with the mixed solution and pressurized. By filling the opposite side of the porous glass membrane with an aqueous solution in which a stabilizer or the like is dissolved, an emulsion composed of uniform particles can be obtained. Thereafter, polymerization is performed by heating or the like, whereby polymer particles having a uniform particle size are prepared. The method of the present invention can be applied to a porous polymer and a non-porous polymer, and a porous polymer particle having a uniform particle size and a uniform non-porous polymer particle can be obtained. The thus produced porous polymer particles having a uniform particle size or non-porous polymer particles having a uniform particle size according to the present invention can be used for various chromatographic methods such as high performance liquid chromatography (HPLC) and capillary electrochromatography (CEC). It can be used as a filler. The particle size of the porous polymer particles having a uniform particle size or the non-porous polymer particles having a uniform particle size can be appropriately set according to the type of chromatography to be used, the type of the substance to be separated, and the like. Desirable particle size is usually from 2 μm to 300 μm, preferably from 2 μm to 20 μm, but is not limited to this range.
本発明の粒子径均一ポリマー粒子に用いられるポリマーの構成単位モノマーと しては、 スチレン、 ジビニルベンゼン、 ジアクリル酸エチレン、 ジメタクリル酸 エチレン、 アタリル酸メチル、 メタクリル酸メチル、 ァクリル酸グリシジル、 メ タクリル酸グリシジル、 アクリルアミ ド、 N, N' —メチレンビスアクリルアミ ド等を挙げることができる。 また、 これらのモノマーを任意に組み合わせて用い ることもできる。  Styrene, divinylbenzene, ethylene diacrylate, ethylene dimethacrylate, methyl acrylate, methyl methacrylate, glycidyl acrylate, methacrylic acid Glycidyl, acrylamide, N, N'-methylenebisacrylamide and the like can be mentioned. These monomers can be used in any combination.
したがって、 本発明の粒子径均一ポリマー粒子に用いられるポリマーとしては、 ポリスチレン、 ポリジビニルベンゼン、 ポリ （スチレン一ジビニルベンゼン） Accordingly, the polymer used for the uniform particle size polymer particles of the present invention includes polystyrene, polydivinylbenzene, and poly (styrene-divinylbenzene).
(スチレンージビニルベンゼン共重合体） 、 ポリ （アクリル酸メチル一ジァクリ ル酸エチレン） 、 ポリ （メタクリル酸メチルージアクリル酸エチレン） 、 ポリ(Styrene divinyl benzene copolymer), poly (methyl acrylate-ethylene diacrylate), poly (methyl methacrylate diethylene acrylate), poly
(アクリル酸メチル一ジメタクリル酸エチレン） 、 ポリ （メタクリル酸メチルー ジメタクリル酸ェチレン） 、 ポリ （ァクリル酸グリシジルージァクリル酸ェチレ ン） 、 ポリ （メタクリル酸グリシジル一ジァクリル酸ェチレン） 、 ポリ （ァクリ ル酸グリシジル一ジメタクリル酸ェチレン） 、 ポリ （メタクリル酸グリシジルー ジメタクリル酸エチレン） 、 ポリ （アクリルアミ ド一N， N' —メチレンビスァ クリルアミ ド） 等を挙げることができる。 (Methyl acrylate-ethylene dimethacrylate), poly (methyl methacrylate-diethylene methacrylate), poly (glycidyl methacrylate diethylene acrylate), poly (glycidyl methacrylate-ethylene diethylene acrylate), poly (acrylic acid) Examples thereof include glycidyl acrylate-diethylene methacrylate), poly (glycidyl methacrylate diethylene methacrylate), and poly (acrylamide-N, N'-methylenebisacrylamide).
本発明の製造方法によって得られる粒子径均一ポリマー粒子では、 粒子径の分 布を表す C V値が 1 0 %前後であればよく、 特に 1 0 %以下であれば好ましいと 言える。  In the polymer particles having a uniform particle size obtained by the production method of the present invention, the CV value representing the distribution of the particle size may be about 10%, and particularly preferably 10% or less.
本発明で用いられるポリマーのうち、 市販のポリマーとしては、 ポリ （スチレ ンージビニルベンゼン） 系、 ポリアクリル酸系、 ポリアクリル酸エステル系、 ポ リメタクリル酸系、 ポリメタクリル酸エステル系、 ポリヒ ドロキンァクリル酸系、 ポリヒ ドロキシアクリル酸エステル系、 ポリヒ ドロキシメタクリル酸系、 ポリヒ ドロキシメタクリル酸エステル系、 ポリカルボン酸ビニル系充填剤等を挙げるこ とができる。 Among the polymers used in the present invention, commercially available polymers include poly (styrene vinyl benzene), polyacrylic acid, polyacrylic ester, Remethacrylic acid type, polymethacrylic acid ester type, polyhydroxyquinacrylic acid type, polyhydroxyacrylic acid ester type, polyhydroxymethacrylic acid type, polyhydroxymethacrylic acid ester type, polyvinyl polycarboxylate type filler etc. Can be.
本発明の粒子径均一多孔性ポリマー粒子を製造するのに用いられる S P G膜乳 化装置としては特に制限はなく、 例えば、 伊勢化学工業社製の M P G膜乳化装置 マイクロキッ 卜を挙げることができる。 実施例  The SPG film emulsifier used for producing the porous polymer particles having a uniform particle size of the present invention is not particularly limited, and examples thereof include an MPG film emulsifier Micro Kit manufactured by Ise Chemical Industry Co., Ltd. Example
以下の実施例により本発明をさらに詳細に説明するが、 本発明は実施例によつ て何ら制限されるものではない。  The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to the examples.
実施例 1 Example 1
(実験方法） モノマーとしてスチレンおよびジビニルベンゼンを用いて、 膜乳 化装置として伊勢化学工業社製の M P G膜乳化装置マイクロキッ トを使用し、 粒 子径が約 5 // mおよび約 3 mとなるように膜を選択して粒子を調製した。 また、 同様のサイズを持つ充填剤を従来法である二段階膨潤重合法によつても調製した。 この際には、 ポリスチレン種粒子を用いた。 得られた粒子は常法により洗浄した 後、 湿式法でステンレススチール製力ラムに充てんしてそのカラム性能等を比較 した。  (Experimental method) Styrene and divinylbenzene were used as monomers, and an MPG membrane emulsifier microkit manufactured by Ise Chemical Industry Co., Ltd. was used as a membrane emulsifier, and the particle diameter was about 5 // m and about 3 m. The membrane was selected so as to obtain particles. A filler having a similar size was also prepared by a conventional two-stage swelling polymerization method. In this case, polystyrene seed particles were used. After the obtained particles were washed by a conventional method, they were packed in a stainless steel power ram by a wet method, and their column performances were compared.
(結果） S P G膜乳化法では、 膜の細孔径とその分布によって、 得られる粒子 のサイズおよびその分布が決定されるため、 一般に粒子径の分布は二段階膨潤重 合法の場合と比較して広くなる傾向がある。 今回二つの方法で調製したポリ （ス チレンージビニルベンゼン） 粒子を比較したところ、 S P G膜乳化法で調製した 充填剤の方が粒子径分布の程度を表す C V値がわずかに大きくなっていることが 分かった。 し力、しなカ ら、 カラムの圧力損失を増大させる微小粒子は含まれてい ないため、 H P L C等のクラマトグラフィー用充填剤として充分に使用可能であ ることが確認された。 なお、 上記の調製法の異なる各粒子は光学顕微鏡により比 較した。 C V値は、 二段階膨潤重合法により得られた粒子では 1 0 %、 S P G膜 乳化法により得られた粒子では 1 0〜1 5 %であった。 微小粒子の不在は光学顕 微鏡により確認した。 (Results) In the SPG membrane emulsification method, the size and distribution of the obtained particles are determined by the pore diameter and the distribution of the membrane. Therefore, the particle size distribution is generally wider than in the two-stage swelling polymerization method. Tend to be. Comparing the poly (styrenedivinylbenzene) particles prepared by the two methods, the filler prepared by the SPG membrane emulsification method has a slightly higher CV value, which indicates the degree of particle size distribution. I understand. As a result, it was confirmed that it could be sufficiently used as a packing material for chromatography such as HPLC because it does not contain microparticles that increase the pressure loss of the column. In addition, each particle having a different preparation method was compared with an optical microscope. The CV value was 10% for particles obtained by the two-step swelling polymerization method, and 10 to 15% for particles obtained by the SPG film emulsification method. Optical microscopy It was confirmed with a microscope.
ステンレススチール製力ラムに湿式充てんしたが、 双方の粒子で同様の充てん 方法を用いることが可能であった。 また、 充てんしたカラムの圧力損失は、 以下 に示すように、 逆相条件下でほとんど差が見られなかった。  The stainless steel force ram was wet-filled, but a similar packing method could be used for both particles. In addition, the pressure drop of the packed column showed almost no difference under reversed phase conditions as shown below.
(二段階膨潤重合法） (Two-step swelling polymerization method)
粒子径約 5//m ; 2. 4MP a Particle size about 5 // m; 2.4MPa
粒子径約 3〃m ; 7. 4MP a Particle size about 3〃m; 7.4MPa
(S PG膜乳化法） (SPG membrane emulsification method)
粒子径約 5〃m； 2. 3MP a Particle size about 5〃m; 2.3MPa
粒子径約 3 /m ; 9. 6MP a このことは、 S PG膜乳化法で調製した粒子が予想どおり圧力損失の主な原因 となる微小粒子を含んでいないことを示している。 Particle size of about 3 / m; 9.6MPa This indicates that the particles prepared by the SPG membrane emulsification method do not contain, as expected, the fine particles that are the main cause of pressure loss.
アルキルベンゼンを溶質とする 80%ァセトニトリル中での評価では、 理論段 数において、 約 3 の粒子を充てんしたカラムで約 15000段、 約 5 mの 粒子を充てんしたカラムで約 8000段の理論段数を与え、 S PG膜乳化法で調 製した粒子においても二段階膨潤重合法で調製した粒子と全く遜色の無いカラム 性能が得られることが示され、 カラムの安定性も良好であった。 これは、 換算理 論段高にすると約 3程度となり （理論的には 2が限界とされている） 、 ほぼ限界 の性能が達成されていると言える。  In the evaluation in 80% acetonitrile using alkylbenzene as a solute, the number of theoretical plates was about 15,000 for a column packed with about 3 particles and about 8000 for a column packed with about 5 m particles. It was also shown that the particles prepared by the SPG membrane emulsification method exhibited column performance comparable to that of the particles prepared by the two-step swelling polymerization method, and the column stability was good. This is about 3 when the conversion theory step is raised (theoretically, the limit is 2), and it can be said that almost the limit performance is achieved.
力ラムの安定性については、 二段階膨潤重合法で調製した粒子が種粒子による 粒子球形の破壊により、 カラムの安定性が極度に低下するのに比べて、 SPG膜 乳化法で調製した粒子は完全球形のために、 3 z/m以下の微小粒子においても全 くカラム性能は損なわれなかった。  Regarding the stability of the force ram, the particles prepared by the SPG membrane emulsification method were compared with the particles prepared by the two-stage swelling polymerization method, where the stability of the column was extremely reduced due to the destruction of the particle sphere by the seed particles. Due to the perfect spherical shape, column performance was not impaired at all even for particles as small as 3 z / m or less.
図 1は S PG膜乳化法で調製した約 3 //mの粒子を分離剤として用いた HP L Cによるアルキルベンゼンの分離クロマトグラムを表す。 図 1に示されたアルキ ルベンゼンのクロマ卜グラムは、 それぞれのピークが鋭く、 さらにテーリング等 の著しい変形を示さなかったので、 分析用のカラムとして優れていることを示し ている。 Figure 1 shows the separation chromatogram of alkylbenzene by HP LC using particles of about 3 // m prepared by the SPG membrane emulsification method as a separating agent. The alkylbenzene chromatogram shown in Fig. 1 has sharp peaks, Since no significant deformation was observed, this indicates that the column is excellent as an analytical column.
—方、 テトラヒ ドロフランを移動相としたサイズ排除クロマトグラフィ一によ- て粒子の細孔径分布を求めた。 結果を図 2および図 3に示す。 図に示した M rは 溶質として用いたポリスチレンの分子量、 E 1 u t i 0 n v o l u m eは溶質 の溶出体積である。 図 2は双方の方法で調製した粒子怪約 3 mのポリマ一粒子 の細孔径分布を、 図 3は双方の方法で調製した粒子径約 5 / mのポリマー粒子の 細孔径分布をそれぞれ示す。 図 2および図 3から明らかなように、 双方の方法で 調製した充填剤において細孔径分布に有意な差が認められた。  On the other hand, the pore size distribution of the particles was determined by size exclusion chromatography using tetrahydrofuran as a mobile phase. The results are shown in FIGS. M r shown in the figure is the molecular weight of the polystyrene used as the solute, and E 1 uti0nvolume is the elution volume of the solute. Figure 2 shows the pore size distribution of a polymer particle with a particle size of about 3 m prepared by both methods, and Figure 3 shows the pore size distribution of a polymer particle with a particle size of about 5 / m prepared by both methods. As is clear from FIGS. 2 and 3, a significant difference was observed in the pore size distribution between the fillers prepared by both methods.
すなわち、 二段階膨潤重合法では、 種粒子であるポリスチレンが希釈剤または モノマーに溶解する場合には、 溶解したポリスチレンが高分子希釈剤として機能 し、 結果として、 より大きな細孔を持った多孔性粒子を与える傾向があるが、 S P G膜乳化法では種ポリマーが存在しないために、 高分子希釈剤によって形成さ れる大きな細孔が減少したものと考えられる。 このことは、 種粒子を用いない一 般の懸濁重合法でも同様に見られることから、 S P G膜乳化法では、 より従来法 である懸濁重合法に近い性質を有する充填剤を調製することができる。 産業上の利用の可能性  In other words, in the two-stage swelling polymerization method, when the seed particles, polystyrene, dissolve in the diluent or monomer, the dissolved polystyrene functions as a polymer diluent, resulting in a porous material having larger pores. Although it tends to give particles, it is considered that the large pores formed by the polymer diluent were reduced by the absence of the seed polymer in the SPG membrane emulsification method. This is also observed in a general suspension polymerization method that does not use seed particles.Therefore, in the SPG membrane emulsification method, it is necessary to prepare a filler having properties similar to those of the conventional suspension polymerization method. Can be. Industrial applicability
S P G膜乳化法により粒子径均一多孔性ポリマ一粒子を調製することにより下 記に挙げる利点があり、 今後のクロマ卜グラフィー用ポリマー充填剤合成法の一 つの手法になり得る。  The preparation of porous polymer particles having a uniform particle size by the SPG membrane emulsification method has the following advantages, and can be one of the methods for the synthesis of polymer fillers for chromatography in the future.
1 . 膜の選択により、 任意のサイズの粒子径均一粒子がある程度の粒度分布で調 製できる点。  1. The point that uniform size particles of any size can be prepared with a certain degree of particle size distribution by selecting the membrane.
2 . 装置のサイズを選択することで、 グラムスケールからキログラムスケールま で比較的スケールの大きな調製が可能となる点。  2. A relatively large scale preparation from the gram scale to the kilogram scale is possible by selecting the size of the equipment.
3 . 膨潤重合法では親水性の高い粒子の調製が困難であつたが、 本発明の方法で は連続相を油相とすることで、 親水性の高い粒子の調製が可能である点。  3. Although it was difficult to prepare highly hydrophilic particles by the swelling polymerization method, the method of the present invention allows the preparation of highly hydrophilic particles by using a continuous phase as an oil phase.
4 . 種粒子を使用しないので、 種粒子のポリマー希釈剤としての影響が無い点。 4. Since no seed particles are used, there is no effect of the seed particles as a polymer diluent.
5 . 種粒子が無いので、 3 / m以下の粒子の調製が可能となり、 キヤビラリー電 気クロマトグラフィーなどの充填剤 （1 m程度） の調製が可能である点。5. Because there are no seed particles, particles of 3 / m or less can be prepared. The ability to prepare packing materials (approximately 1 m) for gas chromatography.
6. カラムの安定性が良好であり、 圧力損失も低く押さえられる点。 6. Good column stability and low pressure loss.
7. カラム性能が良好である点。  7. Good column performance.

Claims

請 求 の 範 囲 The scope of the claims
1 . S P G膜乳化法を用いることを特徴とする粒子径均一ポリマー粒子の製造 方法。 1. A method for producing polymer particles having a uniform particle size, characterized by using an SPG film emulsification method.
2 . ポリマーがポリスチレン、 ポリ ジビニルベンゼン、 ポリ （スチレンージビ 二ルペンゼン） の L、ずれかである請求の範囲第 1項記載の製造方法。  2. The method according to claim 1, wherein the polymer is L of polystyrene, polydivinylbenzene, or poly (styrenedivinylbenzene).
3 . ポリマーが多孔性ポリマーである請求の範囲第 1項または第 2項記載の製 造方法。  3. The production method according to claim 1, wherein the polymer is a porous polymer.
4 . ポリマーが無孔性ポリマーである請求の範囲第 1項または第 2項記載の製 造方法。  4. The method according to claim 1, wherein the polymer is a non-porous polymer.
5 . 請求の範囲第 1項に記載された製造方法によつて得られた粒子径均一ポリ マ一粒子を含むクロマトグラフィー用充填剤。  5. A packing material for chromatography comprising polymer particles having a uniform particle size obtained by the production method according to claim 1.
6 . クロマトグラフィ一が高速液体クロマトグラフィ一である請求の範囲第 5 項記載のクロマトグラフィー用充填剤。  6. The packing material for chromatography according to claim 5, wherein the chromatography is high performance liquid chromatography.
7 . ポリマーが多孔性ポリマーである請求の範囲第 5項または第 6項記載のク ロマトグラフィー用充填剤。  7. The filler for chromatography according to claim 5 or 6, wherein the polymer is a porous polymer.
8 . ポリマーが無孔性ポリマーである請求の範囲第 5項または第 6項記載のク ロマトグラフィー用充填剤。  8. The filler for chromatography according to claim 5 or 6, wherein the polymer is a nonporous polymer.
PCT/JP1998/004665 1997-10-15 1998-10-15 Process for producing polymer particles with uniform particle size WO1999019370A1 (en)

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Publication number Priority date Publication date Assignee Title
JP2003524680A (en) * 1999-05-11 2003-08-19 財団法人化学技術戦略推進機構 Affinity control type material using stimulus-responsive polymer and separation / purification method using the material
WO2017204292A1 (en) * 2016-05-25 2017-11-30 昭和電工株式会社 Liquid chromatography filler
US9982090B2 (en) 2014-07-17 2018-05-29 Ultra V Co., Ltd. Method for manufacturing polydioxanone particles for filler
KR20190058923A (en) 2017-11-22 2019-05-30 (주)금양 Process for production of thermally expanded microsphere which particle dispersibility is improved by increasing viscosity of suspension

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003524680A (en) * 1999-05-11 2003-08-19 財団法人化学技術戦略推進機構 Affinity control type material using stimulus-responsive polymer and separation / purification method using the material
US9982090B2 (en) 2014-07-17 2018-05-29 Ultra V Co., Ltd. Method for manufacturing polydioxanone particles for filler
WO2017204292A1 (en) * 2016-05-25 2017-11-30 昭和電工株式会社 Liquid chromatography filler
KR20190058923A (en) 2017-11-22 2019-05-30 (주)금양 Process for production of thermally expanded microsphere which particle dispersibility is improved by increasing viscosity of suspension

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