WO1999019370A1 - Procede de fabrication de particules polymeres a taille uniforme de particules - Google Patents

Procede de fabrication de particules polymeres a taille uniforme de particules 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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WIPO (PCT)
Prior art keywords
particle size
polymer
particles
uniform particle
polymer particles
Prior art date
Application number
PCT/JP1998/004665
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English (en)
Japanese (ja)
Inventor
Ken Hosoya
Kimihiro Yoshizako
Original Assignee
Amersham Pharmacia Biotech K.K.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Amersham Pharmacia Biotech K.K. filed Critical Amersham Pharmacia Biotech K.K.
Publication of WO1999019370A1 publication Critical patent/WO1999019370A1/fr

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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.

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)

Abstract

L'invention concerne un procédé de fabrication de particules polymères à taille uniforme de particules. Ce procédé est caractérisé par l'utilisation de la technique d'émulsification SPG. Il permet d'obtenir une garniture chromatographique poreuse comprenant des particules polymères qui ont une taille uniforme et sont capables d'améliorer les performances d'une colonne et de réduire la perte de pression.
PCT/JP1998/004665 1997-10-15 1998-10-15 Procede de fabrication de particules polymeres a taille uniforme de particules WO1999019370A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP9/282307 1997-10-15
JP28230797 1997-10-15

Publications (1)

Publication Number Publication Date
WO1999019370A1 true WO1999019370A1 (fr) 1999-04-22

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003524680A (ja) * 1999-05-11 2003-08-19 財団法人化学技術戦略推進機構 刺激応答性高分子を用いた親和力制御型材料および該材料を用いた分離精製方法
WO2017204292A1 (fr) * 2016-05-25 2017-11-30 昭和電工株式会社 Phase stationnaire de chromatographie liquide
US9982090B2 (en) 2014-07-17 2018-05-29 Ultra V Co., Ltd. Method for manufacturing polydioxanone particles for filler
KR20190058923A (ko) 2017-11-22 2019-05-30 (주)금양 현탁액의 점도를 높여 입자 분산성을 향상시키는 열팽창성 미소구의 제조 방법

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06228225A (ja) * 1993-02-04 1994-08-16 Hitachi Chem Co Ltd 架橋重合体粒子の製造法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06228225A (ja) * 1993-02-04 1994-08-16 Hitachi Chem Co Ltd 架橋重合体粒子の製造法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
OMI S., ET AL.: "SYNTHESIS OF POLYMERIC MICROSPHERES EMPLOYING SPG EMULSIFICATION TECHNIQUE.", JOURNAL OF APPLIED POLYMER SCIENCE, JOHN WILEY & SONS, INC., US, vol. 51., 1 January 1994 (1994-01-01), US, pages 01 - 11., XP002915801, ISSN: 0021-8995, DOI: 10.1002/app.1994.070510101 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003524680A (ja) * 1999-05-11 2003-08-19 財団法人化学技術戦略推進機構 刺激応答性高分子を用いた親和力制御型材料および該材料を用いた分離精製方法
US9982090B2 (en) 2014-07-17 2018-05-29 Ultra V Co., Ltd. Method for manufacturing polydioxanone particles for filler
WO2017204292A1 (fr) * 2016-05-25 2017-11-30 昭和電工株式会社 Phase stationnaire de chromatographie liquide
KR20190058923A (ko) 2017-11-22 2019-05-30 (주)금양 현탁액의 점도를 높여 입자 분산성을 향상시키는 열팽창성 미소구의 제조 방법

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