JPS61104253A - Porous glass filler for high performance ion exchange chromatography and its preparation - Google Patents

Porous glass filler for high performance ion exchange chromatography and its preparation

Info

Publication number
JPS61104253A
JPS61104253A JP59226593A JP22659384A JPS61104253A JP S61104253 A JPS61104253 A JP S61104253A JP 59226593 A JP59226593 A JP 59226593A JP 22659384 A JP22659384 A JP 22659384A JP S61104253 A JPS61104253 A JP S61104253A
Authority
JP
Japan
Prior art keywords
porous glass
ion exchange
particles
exchange chromatography
high performance
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
Application number
JP59226593A
Other languages
Japanese (ja)
Other versions
JPH0572545B2 (en
Inventor
Seiji Suzuki
誠治 鈴木
Yukio Murakami
村上　幸男
Yoichi Taguchi
陽一 田口
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fujifilm Holdings Corp
Original Assignee
Fuji Photo Film Co Ltd
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 Fuji Photo Film Co Ltd filed Critical Fuji Photo Film Co Ltd
Priority to JP59226593A priority Critical patent/JPS61104253A/en
Priority to EP19850105871 priority patent/EP0161659B1/en
Priority to DE8585105871T priority patent/DE3576409D1/en
Publication of JPS61104253A publication Critical patent/JPS61104253A/en
Publication of JPH0572545B2 publication Critical patent/JPH0572545B2/ja
Granted legal-status Critical Current

Links

Classifications

    • 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
    • B01J20/291—Gel sorbents
    • 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
    • B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
    • B01J20/28002—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their physical properties
    • B01J20/28004—Sorbent size or size distribution, e.g. particle size
    • 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
    • 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
    • B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to 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
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/3021—Milling, crushing or grinding
    • 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
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/3078—Thermal treatment, e.g. calcining or pyrolizing
    • 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
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/3085—Chemical treatments not covered by groups B01J20/3007 - B01J20/3078
    • 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
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
    • B01J20/3204—Inorganic carriers, supports or substrates
    • 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
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
    • B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
    • 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
    • B01J39/00—Cation exchange; Use of material as cation exchangers; Treatment of material for improving the cation exchange properties
    • B01J39/26—Cation exchangers for chromatographic processes
    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C11/00—Multi-cellular glass ; Porous or hollow glass or glass particles
    • C03C11/005—Multi-cellular glass ; Porous or hollow glass or glass particles obtained by leaching after a phase separation step
    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C12/00—Powdered glass; Bead compositions
    • 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
    • B01J2220/00—Aspects relating to sorbent materials
    • B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
    • B01J2220/54—Sorbents specially adapted for analytical or investigative chromatography

Landscapes

  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Geochemistry & Mineralogy (AREA)
  • Materials Engineering (AREA)
  • Physics & Mathematics (AREA)
  • Thermal Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Glass Compositions (AREA)

Abstract

PURPOSE:To obtain a porous glass filler with an average particle size of 0.1-30mum, by a method wherein the phase splitting of soda glass comprising a three-component system of SiO2/B2O3/Na2O is performed by heat treatment and, after coarse grinding and acid elution treatment, finely grinding operation and classification operation are performed and an ion exchange group is subsequently introduced into the surface of each particle. CONSTITUTION:A stock mixture, wherein SiO2=60.3%, B2O3=30% and Na2O=9.7%, is melted under heating and, after quenched to room temp., subjected to phase splitting by heat treatment. Next, thus obtained glass is coarsely ground so as to obtain a particle size of 50mum or more and, after a particle size is adjusted, acid elution treatment is applied to ground glass to obtain porous glass. Subsequently, this porous glass is finely ground by a impact type pin mill while the finely ground one is successively subjected to pneumatic classification and elutrication classification. Next, an ion exchange group is introduced into the surfaces of thus obtained particles. By this method, because fine porous glass particles can be prepared by selecting an average particle size in an arbitrary size within a range of 0.1-30mum, said particles are suitable as the porous glass filler for high performance ion exchange chromatography.

Description

【発明の詳細な説明】 ［発明の分野］ 本発明は、高速イオン交換クロマトグラフィー用充填剤
およびその製造法に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Field of the Invention] The present invention relates to a packing material for high performance ion exchange chromatography and a method for producing the same.

［発明の背景］ 近年、高速液体クロマトグラフィー法（以下、ＨＬＣと
いう）は、測定時間が短時間であり、かつ高分ｇ１爺を
有するため、重要な分離精製技術の一つとしてあらゆる
化学分野で使用されている。[Background of the Invention] In recent years, high-performance liquid chromatography (hereinafter referred to as HLC) has been used in all chemical fields as an important separation and purification technique because of its short measurement time and high content. It is used.

ＨＬＣの代表的な態様としては、高速イオン交換クロマ
トグラフィー、吸着クロマトグラフィー。Typical forms of HLC include high performance ion exchange chromatography and adsorption chromatography.

ゲル浸透クロマトグラフィー、逆相分配クロマトグラフ
ィーなどが知られている。Gel permeation chromatography, reversed phase partition chromatography, etc. are known.

上記のＨＬＣは特に分析化学の分野において汎用されて
いたが、最近では合成ポリマーの分子量分割、天然の各
種蛋白の分離、生体中の血液蛋白の分離、ホルモン類の
分離、更には、生化学分野の酵素、核醜類の分離、医薬
品の分離等などの目的でも利用されるようになっており
、その適用範囲は急速に拡大しつつある。The above-mentioned HLC has been widely used especially in the field of analytical chemistry, but recently it has been used for molecular weight separation of synthetic polymers, separation of various natural proteins, separation of blood proteins in living organisms, separation of hormones, and even in the field of biochemistry. It is now being used for purposes such as the separation of enzymes, nuclear morphs, and pharmaceuticals, and its range of applications is rapidly expanding.

上述のように高速液体クロマトグラフィー法は有用な分
析技術であることから、その分離の迅速　　　　　　を
化、高性能化を更に進めるために、ＨＬＣ装置の改良が
、たとえば、１．充填剤のカラムへの充填法、２．高圧
送液部、３０分離充填カラム、４゜検出部、５．溶離条
件の選択等の各種の観点から行なわれている。As mentioned above, high performance liquid chromatography is a useful analytical technique, and in order to speed up separation and further improve performance, improvements to HLC equipment are needed, such as 1. Method of filling a column with a packing material, 2. High-pressure liquid feeding section, 30 separation packed column, 4° detection section, 5. This is done from various viewpoints such as selection of elution conditions.

上記の内で分離充填カラムの改良は、一般に充填剤の改
良を基礎にしている。ＨＬＣ用充填剤に要求される特性
としては、下記の特性を挙げることができる。Among the above improvements in separation packed columns are generally based on improvements in the packing material. The properties required for HLC fillers include the following properties.

（１）孔径が制御されていること。(1) Pore diameter must be controlled.

ＨＬＣの内、分子篩効果を利用するゲル浸透クロマトグ
ラフィー（以下、ＧＰＣという）においては、固定相粒
子の細孔サイズと溶質分子のサイズとの相対的関係によ
って、溶質の粒子孔内への拡散が可能か否かがきまり、
その結果として溶離時間にずれ（タイムラグ）が生じ、
大きい分子から小さい分子へと順次溶出するものである
。特にアミノ酸、オリゴマー類の低分子量化合物から合
成高分子ポリペプチド等の高分子量化合物にいたる高範
囲の化合物の分離においては、充填剤の細孔も高範囲に
わたって、しかも任意に制御する必要がある。ただし１
分子量が近接している化合物の混合物を分離する際には
、孔径分布のシャープな充填剤が当然要求される。Among HLC, in gel permeation chromatography (hereinafter referred to as GPC) that utilizes the molecular sieve effect, the diffusion of solute into the particle pores is affected by the relative relationship between the pore size of the stationary phase particle and the size of the solute molecule. It is decided whether it is possible or not,
As a result, a time lag occurs in the elution time,
The molecules elute sequentially from large molecules to small molecules. In particular, when separating a wide range of compounds from low molecular weight compounds such as amino acids and oligomers to high molecular weight compounds such as synthetic polymer polypeptides, it is necessary to control the pores of the filler over a wide range and arbitrarily. However, 1
When separating a mixture of compounds with similar molecular weights, a filler with a sharp pore size distribution is naturally required.

従って、高範囲にわたる孔径の制御および孔径分布のシ
ャープさはＧＰＣ用充填剤の重要な品質特性の一つであ
る。Therefore, control of pore size over a wide range and sharpness of pore size distribution are important quality characteristics of fillers for GPC.

（２）粒子径が小さく、かつ粒子が球状であること。(2) The particle size is small and the particles are spherical.

ＨＬＣにおいてピークの広がりを示すパラメーターとし
ては、一般に下記の式に基づく理論段数Ｎが用いられて
おり、Ｎが大きい程カラムの分離性能は良いといえる。In HLC, the theoretical plate number N based on the following formula is generally used as a parameter indicating peak broadening, and it can be said that the larger N is, the better the separation performance of the column is.

Ｎ＝１６　（Ｖｅ／Ｗ）　２ ｖｅ：ピークの溶出容量 Ｗ　：ビーク幅 粒子径を小さくすることにより、固定相における溶質の
拡散平衡時間が短かくなり、Ｗを小さくすることが可能
となる。同時に粒径分布をシャープにするとＮは大きく
なる。これは、粒径分布が広いとカラム中の大小粒子の
間で分離帯が生じるからである、また、■ｅを大きくす
るためには。N=16 (Ve/W) 2 ve: Peak elution volume W: Beak width By reducing the particle size, the diffusion equilibrium time of the solute in the stationary phase becomes shorter, making it possible to reduce W. At the same time, if the particle size distribution is made sharper, N becomes larger. This is because if the particle size distribution is wide, a separation zone will occur between large and small particles in the column, and also in order to increase ``e''.

細孔容積を大きくし、かつ全多孔性であることが必要で
ある。It is necessary to have a large pore volume and total porosity.

また更に粒子形状を球状にすることも重要である０粒子
形状の球状化により粒子間空隙が小さくなるため、保持
容量が増大し、また移動相の流れが均一となり、渦流、
異常流路の発生を防ぐことができるからである。Furthermore, it is important to make the particle shape spherical. By making the particle shape spherical, the interparticle voids become smaller, increasing the holding capacity and making the flow of the mobile phase uniform, resulting in vortices,
This is because it is possible to prevent the occurrence of abnormal flow paths.

（３）安定な硬質ゲルであること。(3) It must be a stable hard gel.

ＨＬＣの高性能化のため充填剤の粒子径を小さくすると
、圧力損失が大きくなり、一定の流速を得るためには必
然的に高圧をかける必要がある。When the particle size of the filler is reduced in order to improve the performance of HLC, pressure loss increases, and it is inevitably necessary to apply high pressure to obtain a constant flow rate.

従って、充填剤は高圧下であっても、変形、破損を生ず
ることのないように、機械的強度が大きく、また化学的
にも膨潤、収縮及び変性の生じないことが必要である。Therefore, the filler must have high mechanical strength so as not to be deformed or damaged even under high pressure, and must also be chemically free from swelling, shrinkage, and denaturation.

ＨＬＣ用充填剤としては、従来より硬質タイプとしてシ
リカゲル、多孔質ガラス粒子など、半硬質タイプとして
ポリスチレン粒子など、そして軟質タイプとしてポリア
クリルアミド粒子、多糖類ゲルなどが市販され、利用さ
れている。As fillers for HLC, hard types such as silica gel and porous glass particles, semi-hard types such as polystyrene particles, and soft types such as polyacrylamide particles and polysaccharide gel have been commercially available and used.

これらの内で、軟質ゲルは膨潤、収縮、圧力変形がある
ためにＨＬＣには適さない、半硬質タイプは有機溶媒系
充填剤として一般的に使用されているが、特殊な表面修
飾をしない限り水系には適用することができず、使用す
る溶媒に制限かある。一方、シリカゲルの欠点は孔径制
御範囲が比較的狭く（約５０ＯＡ＠以下）、巨大細孔が
得がたいこと、また細孔分布が悪い（広い）ために、分
子量が近接した物質量の分離には適当とはいうことはで
きない、また、たとえば、シリカゲル粒子の表面に、イ
オン交換基を導入する表面処理を施して高速イオン交換
クロマトグラフィー用の充填剤として利用しようとして
も、粒子表面に微細孔が多くあるため、実用上充分な程
度の表面処理を施すことが困難である。Among these, soft gels are not suitable for HLC due to swelling, shrinkage, and pressure deformation, while semi-rigid gels are commonly used as organic solvent-based fillers, but unless special surface modification is performed, soft gels are not suitable for HLC. It cannot be applied to aqueous systems, and there are restrictions on the solvents that can be used. On the other hand, the disadvantages of silica gel are that the pore size control range is relatively narrow (approximately 50 OA@ or less), it is difficult to obtain large pores, and the pore distribution is poor (wide), making it unsuitable for separating amounts of substances with close molecular weights. For example, even if the surface of silica gel particles is treated to introduce ion-exchange groups and used as a packing material for high-speed ion-exchange chromatography, there are many micropores on the particle surface. Therefore, it is difficult to perform surface treatment to a practically sufficient degree.

シリカゲルの欠点をカバーし、優れた孔特性をもつ充填
剤としては多孔質ガラス粒子がある。多孔質ガラス粒子
の一般的な製法は、米国特許第　　　　　　　−２，１
０６，７４４号、第２，２２１，７０９号、第３．５４
９．５２４号、第３　、７５８　。Porous glass particles are fillers that overcome the shortcomings of silica gel and have excellent pore properties. A general method for manufacturing porous glass particles is described in U.S. Pat.
No. 06,744, No. 2,221,709, No. 3.54
9.524, No. 3, 758.

２８４号等の明細書に、また「数誌Ｊ　４　（４）２２
１〜２２７（１９７９）、「巨大粒子のゲルパーミエイ
ションクロブトグラフィー」　３〜１８（１９８０）に
記載がある。しかしながら、これらの刊行物に記載され
ているの製法によっては、ＨＬＣ用に適した微小な粒子
からなる多孔質ガラス（粒子直径が約３０ＪＬｍ以下の
もの）を製造することは困難である。In the specifications of No. 284, etc., there is also a
1-227 (1979) and "Gel Permeation Chromotography of Giant Particles" 3-18 (1980). However, depending on the manufacturing methods described in these publications, it is difficult to manufacture porous glass made of fine particles (having a particle diameter of about 30 JLm or less) suitable for HLC.

［発明の目的］ 本発明は、高速液体クロマトグラフィーの代表的態様の
ひとつである高速イオン交換クロマトグラフィーを実施
するための装置において用いるのに適した多孔質ガラス
充填剤を提供することを目的とするものである。[Object of the invention] The object of the present invention is to provide a porous glass packing material suitable for use in an apparatus for performing high-speed ion exchange chromatography, which is one of the typical embodiments of high-performance liquid chromatography. It is something to do.

［発明の要旨］ 本発明は、Ｓ　ｉ　Ｏ２’　Ｂ　２０　ｚ　”　Ｎ　ａ
　２０　（１’）三成分系からなる高硅酸多孔質ガラス
微粒子であって、該微粒子の平均直径が０．１〜３０μ
ｍであり、かつ粒子表面にイオン交換基を有することを
特徴とする高速イオン交換クロマトグラフィー用多孔質
ガラス充填剤からなるものである。　　。[Summary of the Invention] The present invention provides S i O2′ B 20 z ” N a
20 (1') High silicic acid porous glass fine particles consisting of a three-component system, the average diameter of the fine particles being 0.1 to 30μ
The material is made of a porous glass filler for high performance ion exchange chromatography, which is characterized by having an ion exchange group on the particle surface. .

上記の高速イオン交換クロマトグラフィー用多孔質ガラ
ス充填剤は、５ｉ０２・Ｂ２０．・Ｎａ２Ｏの三成分系
の分相性硼硅酸ソーダガラスに熱処理を施して分相させ
た後、酸溶出処理により酸可溶性相の少なくとも一部を
溶出除去して得られる多孔質ガラス粒子を、微粉砕操作
と分級操作とにかけることに”よって平均直径０．１〜
３０ＩＬｍの多孔質ガラス微粒子を得て、次いで該粒子
の表面にカチオン交換基あるいは７ニオン交換基などの
イオン交換基を導入する方法により有利に製造すること
かでざる。The above porous glass packing material for high speed ion exchange chromatography is 5i02/B20.・After heat-treating Na2O three-component phase-splitting sodium borosilicate glass to phase-separate it, at least a portion of the acid-soluble phase is eluted and removed through acid elution treatment, resulting in fine porous glass particles. By applying crushing and classifying operations, the average diameter is 0.1~
Advantageously, it can be produced by a method in which porous glass fine particles of 30 ILm are obtained and then an ion exchange group such as a cation exchange group or a 7-ion exchange group is introduced onto the surface of the particles.

［発明の詳細な記述］ 本発明に用いる多孔質ガラスとは５ｉ０２、Ｂ２０．、
Ｎａ２Ｏよりなる三成分系の高硅酸ガラスであり、特定
組成範囲の分相現象を利用して製造するものである。上
記の三成分系の高硅酸ガラスから多孔質ガラス粒子を製
造する方法は、たとえば、前掲の各刊行物に記載されて
いて、公知である、従って、以下においてはその製造法
の代表例を示す。[Detailed Description of the Invention] The porous glass used in the present invention is 5i02, B20. ,
It is a three-component high silicate glass made of Na2O, and is manufactured by utilizing the phase separation phenomenon in a specific composition range. The method for producing porous glass particles from the above-mentioned three-component high silicate glass is described, for example, in the publications listed above, and is well known. Therefore, typical examples of the production method will be described below. show.

５ｉ０２、ＢａＯ２、Ｎａ２Ｏの原料混合バー。5i02, BaO2, Na2O raw material mixing bar.

チを白金ルツボに入れ、１３００−１４５０℃で熔解す
る。融解物を室温まで急冷した後、５００〜７００℃で
分相熱処理を施す、この処理によって融解物の内部にお
いて５ｉ０２リツチ相とＢ２Ｏ３・Ｎ＆２０リッチ相と
の分離が行なわれる。この分離の際には、各分離相が互
いに絡み合った絡み合い構造を呈し、各分離相のサイズ
は分相熱処理の温度と時間により任意に制御することが
可能である。熱処理後、冷却物を粉砕機で粒子直径約５
０４ｍ以上に粉砕する。ついで、酸可溶性のＢ２Ｏ２・
Ｎａ２Ｏ相を溶出して多孔質にするために、塩酸などの
無機酸を用い加熱下（例、約９０℃）で酸処理をする。Put the chi into a platinum crucible and melt at 1300-1450°C. After the melt is rapidly cooled to room temperature, it is subjected to a phase separation heat treatment at 500-700 DEG C. This treatment separates the 5i02-rich phase and the B2O3.N&20-rich phase within the melt. During this separation, the separated phases exhibit an entangled structure in which they are entangled with each other, and the size of each separated phase can be arbitrarily controlled by the temperature and time of the phase separation heat treatment. After heat treatment, the cooled material is crushed into particles with a diameter of approximately 5
Grind to 0.4m or more. Then, acid-soluble B2O2
In order to elute the Na2O phase and make it porous, acid treatment is performed using an inorganic acid such as hydrochloric acid under heating (eg, about 90° C.).

この酸処理によってＢ２０．・Ｎａ２Ｏ相は溶出し、こ
れにより多数の細孔を有する５ｆ０２リツチの骨格相が
生成する。この細孔にはコロイド状シリカが残存し、残
存し細孔は一部閉塞しているので、アルカリ水溶液（例
、ｌ　／　２　Ｎ　−Ｎ　ａ　ＯＨ水溶液）を用いてコ
ロイド状シリカを溶出する。その後、水洗・酸洗・水洗
を繰り返し細札内を洗浄し、多孔質ガラスを得る。By this acid treatment, B20. - The Na2O phase is eluted, thereby forming a 5f02-rich skeletal phase with numerous pores. Colloidal silica remains in these pores, and since the remaining pores are partially blocked, the colloidal silica is eluted using an alkaline aqueous solution (eg, 1/2 N-NaOH aqueous solution). Thereafter, the inside of the bill is washed by repeating water washing, pickling, and water washing to obtain porous glass.

しかしながら、上記のような方法を利用して粒子直径３
０ｇｍ以下の微粒子多孔質ガラスを製造した例はこれま
でに報告されていない、その理由としては、単にそのよ
うな試みがこれまでになされていないとも考えられるが
、他の理由として。However, using the above method, particle diameter 3
No example of producing porous glass with microparticles of 0 gm or less has been reported to date. This may be because no such attempt has been made, but there are other reasons as well.

上記の方法のみによっては粒子直径３０μｍ以下の微粒
子多孔質ガラスを製造が著しく困難であることが挙げら
れるであろう、すなわち、上記の方法においては、コロ
イド状シリカを溶出するためにアルカリ水溶液を施すが
、この時３０４ｍ以下の微粒子も同時に溶解するからで
ある。It may be mentioned that it is extremely difficult to produce fine-particle porous glass with a particle diameter of 30 μm or less using only the above method. In other words, in the above method, an alkaline aqueous solution is applied to elute the colloidal silica. However, at this time, fine particles of 304 m or less are also dissolved at the same time.

本発明者の検討によれば、上記のようにして製造された
多孔質ガラスに対して微粉砕操作と分級操作とを施すこ
とによって、ＨＬＣ用充填剤として適した平均粒子直径
約０．１〜３０μｍ以下、　　　　　　−望ましくは１
−１０　ｐ、　ｍの微粒子状多孔質ガラスが得られるこ
とを見出した。以下に、多孔質ガラスに対して施す微粉
砕操作と分級操作とを例を挙げて説明する。According to the studies of the present inventors, by subjecting the porous glass produced as described above to a fine pulverization operation and a classification operation, an average particle diameter of about 0.1 to 30 μm or less, - preferably 1
It has been found that a fine particulate porous glass having a particle diameter of -10 p, m can be obtained. Below, the pulverization operation and classification operation performed on porous glass will be explained by giving examples.

前記のようにして製造した多孔質ガラスを、たとえば、
まず衝Ｉｌ型ピンミルで微粉砕する。該ピンミルは接粉
Ｉｆしてはジルコニア製の抗摩耗性セラミックでライニ
ングしたものを使用することが望ましい、これは金属粉
の混入を防ぐためである。金ａｍピンミルを使用すると
摩耗が著しく。For example, the porous glass produced as described above is
First, it is pulverized using a type Il pin mill. It is desirable to use a pin mill lined with an anti-wear ceramic made of zirconia for powder contact, in order to prevent metal powder from being mixed in. If you use a gold am pin mill, there will be significant wear.

多孔質ガラス中に混入した微粒子金属粉は、たとえ強力
な磁性分離装置を通しても多孔質ガラスと分離すること
は困難である。It is difficult to separate fine metal powder mixed into porous glass from the porous glass even through a strong magnetic separation device.

次に遠心力型気流分級機で粗分縁する。気流分級操作だ
げでは、ＨＬＣ充填剤として必要な粒度分布を得ること
は難しいが、のちの工程の水篩分級の効率向上のために
は、この粗分縁を行なうことが望ましい。Next, it is roughly separated using a centrifugal air classifier. Although it is difficult to obtain the particle size distribution necessary for an HLC filler by air classification alone, it is desirable to carry out this rough separation in order to improve the efficiency of water sieve classification in the later step.

次に水篩分級を行なう、二の水篩分級は通常のストーク
ス沈降原理に甚くものであるが、水篩回数を数回〜十数
回必要とする０分散媒は水が最も好ましいが、必要に応
じてグリセリン、ポリエチレングリコール類の増粘剤を
添加し、沈降速度を制御することも可能であり、またへ
キサメタリン厳ナトリウム、ビロリン酸ナトリウム、ド
デシル硫酸ナトリウム等の界面活性剤を添加することに
より、粒子の分散性を向上することも出来る。そして、
最後に水洗乾炊して、微粒子多孔質ガラスが完成する。Next, water sieve classification is carried out. The second water sieve classification is extremely similar to the usual Stokes sedimentation principle, but water is the most preferable dispersion medium that requires water sieving several times to more than ten times. If necessary, thickeners such as glycerin and polyethylene glycols can be added to control the sedimentation rate, and surfactants such as sodium hexamethalin, sodium birophosphate, and sodium dodecyl sulfate can also be added. This also makes it possible to improve the dispersibility of the particles. and,
Finally, the glass is washed with water and dried to complete the fine-particle porous glass.

上記の微粉砕操作と分級操作により得られる微粒子化さ
れた多孔質ガラスの物理、化学的性質の例を以下に示す
。Examples of physical and chemical properties of micronized porous glass obtained by the above-mentioned pulverization and classification operations are shown below.

（１）孔特性 ■）平均孔径の範囲：孔直径＝８０〜３０００Ａ（この
範囲で任意の孔 孔径のものが製造可） ２）孔径分布（累積１０．９０％点基準）：≦±１５％ ３）孔容積：約０．８ｍＪＬ／ｇ ４）比表面ｉａ＝約１０〜２５０ｍ２／ｇ（２）粒度分
布 ｌ）平均粒径：粒子直径＝０．１〜３０μｍ２）粒度分
布（累Ｊｆｉ１０．９０％点基準）：≦±３５％ （３）他の物理化学的性質 ｌ）化学組成：５ｉ０２９２％。(1) Pore characteristics ■) Average pore size range: pore diameter = 80 to 3000A (any pore size within this range can be manufactured) 2) Pore size distribution (cumulative 10.90% point standard): ≦±15% 3) Pore volume: approximately 0.8 mJL/g 4) Specific surface ia = approximately 10 to 250 m2/g (2) Particle size distribution l) Average particle size: particle diameter = 0.1 to 30 μm2) Particle size distribution (cumulative Jfi 10.90 (% point standard): ≦±35% (3) Other physicochemical properties l) Chemical composition: 5i0292%.

Ｂ２Ｏ３７％ Ｎａ２Ｏ＜ｌｖｔ％ ２）真比重＝２．２ ３〕高比重＝０．５０ ４）シラノール基；約１．５ｐモル／ｍ’（トルエン中
のメチルレッド吸着、ｉｌ測定値に基づいた計算値） ５）＃高温性＝６００℃迄使用可 ６）線熱膨張係数ｘ８Ｘｌｏ−’ａｍ／ｃｍａ℃（６０
０℃迄） 上記の微粒子状多孔質ガラスは、その表面にシラノール
基を有するため、通常はその表面にシランカップリング
処理剤による処理などの前処理を施したのち、カチオン
交換基あるいはアニオン交換基などのイオン交換基を導
入する。B2O37% Na2O<lvt% 2) True specific gravity = 2.2 3] High specific gravity = 0.50 4) Silanol group; approximately 1.5 pmol/m' (calculation based on methyl red adsorption in toluene, il measurement value) Value) 5) #High temperature resistance = Can be used up to 600℃ 6) Linear thermal expansion coefficient x8Xlo-'am/cma℃ (60
(up to 0°C) The above-mentioned fine particulate porous glass has silanol groups on its surface, so the surface is usually pretreated with a silane coupling treatment agent and then treated with a cation exchange group or anion exchange group. Introducing an ion exchange group such as

′＃、ａ物粒子の表面にカチオン交換基あるいは７ニオ
ン交換基などのイオン交換基を導入する技術は既に各種
類られており５本発明の微粒子状多孔質ガラスの表面に
イオン交換基を導入するに際しても、それらの公知の技
術を利用することができる１本発明の微粒子状多孔質ガ
ラスの表面にイオン交換基を導入するに際して、通常は
先ずその表面にシランカップリング処理を施す。'#, There are already various types of techniques for introducing ion exchange groups such as cation exchange groups or 7 anion exchange groups on the surface of a-product particles. In order to introduce ion exchange groups into the surface of the fine particulate porous glass of the present invention, the surface is usually first subjected to a silane coupling treatment.

ガラス表面のシランカップリング無理用の処理剤として
は各種のものが知られており１本発明においてもそれら
の公知のシランカップリング処理剤を任意に用いること
ができる。また同様なシランカップリング処理はシリカ
ゲルについても公知である。Various types of treatment agents for preventing silane coupling on glass surfaces are known, and any of these known silane coupling treatment agents can be used in the present invention. Similar silane coupling treatments are also known for silica gel.

たとえば、親木性表面改質のために用いられるシランカ
ップリング剤の例としては、γ−グリシドキシプロピル
トリメトキシシラン、ジメチル−γ−グリシオキシプロ
ビルメトキシシラン、３−アミノプロビルトリメトキシ
シテン、およびγ−（２−アミノエチル）アミノプロビ
ルトリメトキ　　　　　ｔジシランを挙げることができ
る。For example, examples of silane coupling agents used for wood-philic surface modification include γ-glycidoxypropyltrimethoxysilane, dimethyl-γ-glycioxypropylmethoxysilane, and 3-aminopropyltrimethoxysilane. Mention may be made of silane, and γ-(2-aminoethyl)aminopropyltrimethodisilane.

疎水性表面改質のために用いられるシランカップリング
剤の例としては、フェニルトリクロロシラン、ジフェニ
ルジクロロシラン、３−フェニルプロピルトリクロロシ
ラン、３−クロロプロピルトリクロロシラン、および２
−フェニルエチルトリクロロシランを挙げることができ
る。Examples of silane coupling agents used for hydrophobic surface modification include phenyltrichlorosilane, diphenyldichlorosilane, 3-phenylpropyltrichlorosilane, 3-chloropropyltrichlorosilane, and 2-chloropropyltrichlorosilane.
-Phenylethyltrichlorosilane may be mentioned.

微粒子状多孔質ガラスの表面を上記のようなシランカッ
プリング剤を用いて処理したのち、カチオン交換基ある
いはアニオン交換基などのイオン交換基を公知の方法に
従い導入する。そのようなイオン交換基の例としては下
記の構造式にて表される基を挙げることができる。After the surface of the particulate porous glass is treated with the above-mentioned silane coupling agent, an ion exchange group such as a cation exchange group or an anion exchange group is introduced according to a known method. Examples of such ion exchange groups include groups represented by the following structural formula.

−（ＣＨ２）ｎ−Ｂｚ−５Ｏ３Ｎａ ［ｎは１〜３の整数を表し、Ｂｚはベンゼン環を表す、
以下同じ］ −（ＣＨ２）　ｎ　Ｓ　Ｏｚ　Ｎ　＆ −（ＣＨ２）ｎ　ＮＨ（ＣＨ２）　２ｓＯｘ　Ｎａ−（
ＣＨ２）ＴＩ　Ｃ０２Ｎａ −（Ｃ）Ｉ２　）　ｙｌ　Ｎｌ（（ＣＨ２）　２　ＣＯ
２Ｎ　ａ−ＣＣＨ２）ｚ　　０ＣＨ２ＣＭ（ＯＨ）Ｃ）
１２　０ＣＨ２Ｃ０２Ｈａ−（Ｃｎｚ）ｎ　ＮＨＣＯ（
ＣＨ２）２　ＣＯ２Ｎ　＆−ＣＣＨｚ　）　　ａ　　０
ＧＨ２０Ｈ（ＯＨ）ＧＨｚ　ＮＨ（ＣＨ２）　　ｚ　Ｓ
０３　Ｈａ−（Ｃ）Ｉ　２　）　　ｎ　Ｎ　”　Ｒ’　
Ｒ”　Ｒ３［Ｈｌ、ｌ！およびＲ３はＣＨ，、Ｃ２Ｈ５
゜Ｃｚ　Ｈ７、Ｂ　Ｚ　−ＣＨ２−１Ｂｚ−など］−（
ＣＣＨ２ｎ　Ｎ＋ＨＲ”　Ｒ” ［Ｒ”　及ヒＲ”　４＊　ＣＨ：４、Ｃ２Ｈ，、Ｃ３Ｈ
７、Ｂｚ−Ｃ）（２−１Ｂｚ−など］ −（ＣＣＨ２３０ＣＨ２ＣＨ（ＯＨ）ＣＨ２ＮＦｌ［Ｒ
は、ＣＨ，、Ｃ２Ｈ５など］ 本発明の充填剤のカラムへの充填は通常の湿式スラリー
充填法で可能である。-(CH2)n-Bz-5O3Na [n represents an integer of 1 to 3, Bz represents a benzene ring,
The same applies below] -(CH2) n S Oz N & -(CH2)n NH(CH2) 2sOx Na-(
CH2)TI C02Na -(C)I2)yl Nl((CH2)2CO
2N a-CCH2)z 0CH2CM(OH)C)
12 0CH2C02Ha-(Cnz)n NHCO(
CH2)2 CO2N &-CCHz) a 0
GH20H(OH)GHz NH(CH2)z S
03 Ha-(C)I2)nN''R'
R” R3 [Hl, l! and R3 are CH,, C2H5
゜Cz H7, B Z -CH2-1Bz-, etc.] -(
CCH2n N+HR” R” [R” and HiR” 4* CH:4, C2H,, C3H
7, Bz-C) (2-1Bz- etc.) -(CCH230CH2CH(OH)CH2NFl[R
is CH,, C2H5, etc.] The packing material of the present invention can be packed into a column by a normal wet slurry filling method.

以下に本発明の実施例を記載する。Examples of the present invention are described below.

［実施例１］ （１）微粒子多孔質ガラス素材の調製 ケイ砂、ホウ酸および硝酸ナトリウムを原料として、鹸
化物換算の組成がＳ　ｉ　Ｏ２”　６０　、３％、Ｂｚ
Ｏｚ＝３０．０％、Ｎａ２０＝９．７％（いずれも重量
％）となるようにボールミルで均−に混合して８０ｋｇ
の原料混合物を得た。この原料混合物を白金ルツボに入
れ、電気炉中で１３５０℃で１０時間攪拌しながら熔解
した６次いで室温迄急冷し、５５０℃で９６時間分相熱
処理を施した。そののちクロスビータ−ミルで粗粉砕し
、篩分機で８０〜４００メツシユに粒度を整え、３Ｎ塩
酸を用い、９０℃で２４時間酸処理を行った。水洗後、
ｌ／２Ｎ水酸化ナトリウム溶液を用い、２０〜２５℃で
２時間コロイダルシリカ除去あ理を行なった。[Example 1] (1) Preparation of fine particle porous glass material Using silica sand, boric acid and sodium nitrate as raw materials, the composition in terms of saponified matter is S i O2” 60, 3%, Bz
Mix evenly with a ball mill so that Oz = 30.0% and Na20 = 9.7% (both weight%) and weigh 80 kg.
A raw material mixture was obtained. This raw material mixture was placed in a platinum crucible and melted in an electric furnace at 1350°C for 10 hours with stirring.Then, it was rapidly cooled to room temperature and subjected to phase separation heat treatment at 550°C for 96 hours. Thereafter, it was coarsely ground using a cross beater mill, adjusted to a particle size of 80 to 400 mesh using a sieve, and acid-treated with 3N hydrochloric acid at 90°C for 24 hours. After washing with water,
Colloidal silica removal treatment was performed at 20 to 25° C. for 2 hours using 1/2N sodium hydroxide solution.

アルカリ溶液を除去するために、十分に水洗を施し、そ
の後ＩＮ塩酸にて、室温で２時間酸洗浄を行なった。Ｐ
Ｈ＝７になるまで水洗を行ない、最後に１００℃で乾燥
を行なって粗粒子多孔質ガラスを作成した。In order to remove the alkaline solution, it was thoroughly washed with water, and then acid-washed with IN hydrochloric acid at room temperature for 2 hours. P
Washing with water was carried out until H=7, and finally drying was carried out at 100°C to produce coarse particle porous glass.

このサンプルの特性は平均孔径１７０Ａ、比孔容８ｔｏ
、８１ｍｆＬ／ｇ、孔径分布＋２１７−１５％、比表面
積１６２ｍ２／ｇ、シラノール基？２フルモル／ｇであ
った。孔特性の測定は水銀圧入法により、比表面積はＢ
、Ｅ、Ｔ法により、そしてシラノール基はメチルレッド
吸着法によって行なった・ 上記の粗粒子多孔質ガラスを衝撃型ビンミルで微粉砕後
、気流分級機を用い分級点４．０Ｂｍ及び６．０Ｂｍで
分級し、この４．０〜６．０ｇｍの粒子を水篩分級にか
けた。The characteristics of this sample are an average pore diameter of 170A and a specific pore volume of 8to.
, 81mfL/g, pore size distribution +217-15%, specific surface area 162m2/g, silanol group? It was 2 full mol/g. The pore characteristics were measured by mercury intrusion method, and the specific surface area was B
, E, T method, and silanol groups were determined by methyl red adsorption method. The particles of 4.0 to 6.0 gm were classified using a water sieve.

水篩分級は沈降高さ１０ｃｍ、沈降時間１．５及び２．
０時間にて１０回繰り返し行なった０分散媒は純水とし
た。最後に１００℃で真空乾燥を行ない、微粒子状多孔
質ガラスを得た。得られた微粒子状多孔質ガラスの粒度
特性は、平均粒径（Ｉ）５０）　＝　５　、０　ｇｍ、
粒度分布（Ｄ　’ＪＯ／　Ｄ　５０）＝１．３０、粒度
分布（Ｄ５０／ＤＩＯ）　＝　１　、３１であった。Water sieve classification was performed using a settling height of 10 cm and a settling time of 1.5 and 2.
Pure water was used as the dispersion medium in which the test was repeated 10 times for 0 hours. Finally, vacuum drying was performed at 100° C. to obtain a fine-particle porous glass. The particle size characteristics of the obtained microparticulate porous glass are as follows: average particle size (I) = 5, 0 gm;
Particle size distribution (D'JO/D50)=1.30, particle size distribution (D50/DIO)=1.31.

（２）イオン交換基の導入 上記の（１）で製造した微粒子状多孔質ガラス表面に下
記の方法によってカチオン交換基を導入した。(2) Introduction of ion exchange groups A cation exchange group was introduced onto the surface of the fine particulate porous glass produced in (1) above by the following method.

微粒子状多孔質ガラス５ｇをｌｏｏｍｉの乾燥ジオキサ
ン中で２−フェニルエチルトリクロロシラン２ｍＡと共
に６時間加熱還流させてガラス粒子表面に２−フェニル
エチル基を導入した１反応終了後ジオキサン、７セトン
、およびメタノールを順次用いてガラス表面を充分洗浄
し１次いで乾燥−させた０次にこれを７００ｍＪＬのク
ロロホルム中でクロルスルホン酸Ｓｍｉと共に加熱還流
させることによりスルホ基を導入した。この処理により
微粒子状多孔質ガラスの表面に強力チオン交換基［−（
ＣＨｚ）　２−ベンゼン環−５Ｏｘ　Ｍａｌが導入され
た。5 g of fine particulate porous glass was heated under reflux with 2 mA of 2-phenylethyltrichlorosilane in dry dioxane of Loomi for 6 hours to introduce 2-phenylethyl groups onto the surface of the glass particles. After completion of the reaction, dioxane, 7 setone, and methanol were added. The glass surface was thoroughly washed using the following methods and then dried.Next, the glass surface was heated and refluxed with chlorosulfonic acid Smi in 700 mJL of chloroform to introduce a sulfo group. Through this treatment, the surface of the fine particulate porous glass has a strong thione exchange group [-(
CHz) 2-benzene ring-5Ox Mal was introduced.

（３）微粒子状多孔質ガラス充填剤の評価上記の強力チ
オン交換基を有する微粒子状多孔質ガラス充填剤を用い
、下記の条件にて高速イオン交換クロマトグラフィーを
実施した。(3) Evaluation of fine particulate porous glass filler Using the above fine particulate porous glass filler having a strong thione exchange group, high speed ion exchange chromatography was carried out under the following conditions.

ＸＳ：ウリジン・グアノシン・７デノシン・シチジン混
合物 （１：ｌ：１：１、重量比） カラムサイズ：径４ｍｍＸ長さ１５０ｍｍ溶離液：　０
．０５Ｍ−ＨＣ０２ＮＨ４を１０％含有するエタノール
φ水溶媒（ｐＨ４，７）流速：１．Ｏｍ愛／分 温度：５０℃ 得られたチャートを第１図に示しＮ、第１図におい、て
、ピーク記号Ｕ、（、、Ａ、Ｃ４士それぞれ、ウリジン
（ｕ）、　グアノシン（Ｇ）、アデノシン（Ａ）、シチ
ジンＣＣ）の各ピークを意味する。XS: Uridine/Guanosine/7denosine/Cytidine mixture (1:l:1:1, weight ratio) Column size: Diameter 4mm x Length 150mm Eluent: 0
．． Ethanol φ water solvent containing 10% of 05M-HC02NH4 (pH 4,7) Flow rate: 1. Om/min Temperature: 50°C The obtained chart is shown in Figure 1. It means each peak of adenosine (A) and cytidine CC).

第１図から明らかなように、本発明の微粒子状多孔質ガ
ラス充填剤を用１．Ｎた高速イオン交換グロマトグラフ
イーによって類似の分子量、イヒ学構造を有する化合物
の混合物が高精度で分離できることが確認された。As is clear from FIG. 1, the fine particulate porous glass filler of the present invention was used in 1. It was confirmed that mixtures of compounds with similar molecular weights and chemical structures can be separated with high precision by high-speed ion-exchange chromatography using nitrogen.

〔実施例２コ 実施例１の（１）で製造した微粒子状多孔質ガラス表面
に下記の方法によって７ニオン交換基を導入した。[Example 2] A 7-ion exchange group was introduced into the surface of the particulate porous glass produced in Example 1 (1) by the following method.

微粒子状多孔質ガラス５ｇを５０℃見の乾燥ジオキサン
中で３−クロロプロビルト１ノグロロシラン１．５ｍｌ
と共に６時間加熱還流させてガラス粒子表面に３−クロ
ロプロピル基を導入した０反応終了後ジオキサン、アセ
トン、およびメタノ−ルを順次用いてガラス表面を充分
洗浄し、次いで乾燥させた。5 g of particulate porous glass was mixed with 1.5 ml of 3-chloroprobilt-1-nochlorosilane in dry dioxane at 50°C.
After the completion of the reaction in which 3-chloropropyl groups were introduced into the surface of the glass particles by heating under reflux for 6 hours, the glass surface was thoroughly washed with dioxane, acetone, and methanol in this order, and then dried.

次に上記処理を施した微粒子状多孔質ガラスを２５ｍ１
のジオキサン中でジエチルアミン２０ｍ文と共に加熱還
流させることによツて該微粒子状多孔質ガラスの表面に
強アニオン交換基［−（（：Ｈｚ　）　３−Ｎ”　（Ｃ
Ｈｚ　）　２　（Ｃ２Ｈ５）　］が導入された。Next, 25 ml of fine particulate porous glass subjected to the above treatment was
A strong anion exchange group [-((:Hz) 3-N'' (C
Hz) 2 (C2H5)] was introduced.

上記の強アニオン交換基を有する微粒子状多孔質ガラス
充填剤を用い、下記の条件にて高速イオン交換クロマト
グラフィーを実施した。High speed ion exchange chromatography was carried out under the following conditions using the above-mentioned fine particulate porous glass filler having a strong anion exchange group.

試料：サリチル７ミド・カフェイン・アスピリン混合物
（１：１：Ｌ、重量比） カラムサイズ：径４ｍｍＸ長さ１５０ｍｍ溶離液：０．
０５Ｍ−ＮａＮＯｉ　（ｐＨ２−５）流速：　ｌ　、０
ｍ１７分 温度：５０℃ 得られたチャートを第２図に示した。第２図において、
ピーク記号Ｓ、Ｃ，Ａはそれぞれ、サリチルアルデヒド
（Ｓ）、カフェイン（Ｃ）、アスピリン（Ａ）の各ピー
クを意味する。Sample: salicyl 7mide/caffeine/aspirin mixture (1:1:L, weight ratio) Column size: diameter 4 mm x length 150 mm Eluent: 0.
05M-NaNOi (pH2-5) flow rate: l, 0
Temperature at 17 minutes: 50° C. The chart obtained is shown in FIG. In Figure 2,
Peak symbols S, C, and A mean the peaks of salicylaldehyde (S), caffeine (C), and aspirin (A), respectively.

第２図から明らかなように１本発明の微粒子状多孔質ガ
ラス充填剤を用いた高速イオン交換クロマトグラフィー
によって類似の分子量、化学構造を有する化合物の混合
物が高精度で分離できることが確認された。As is clear from FIG. 2, it was confirmed that mixtures of compounds having similar molecular weights and chemical structures can be separated with high precision by high-speed ion exchange chromatography using the particulate porous glass packing material of the present invention.

【図面の簡単な説明】[Brief explanation of the drawing]

第１図および第２図は１本発明の多孔質ガラス充填剤を
用いて実施した高速イオン交換クロマトグラフィー操作
により得られた溶出曲線の例を示すグラフである。 特許出願人　富士写真フィルム株式会社代　　理　　人
　　弁理士　　　柳　川　　泰　　男？ ０２４　　（分） 第２図FIGS. 1 and 2 are graphs showing examples of elution curves obtained by high-speed ion exchange chromatography using the porous glass packing material of the present invention. Patent applicant: Representative of Fuji Photo Film Co., Ltd. Patent attorney: Yasushi Yanagawa Male? 024 (minutes) Figure 2

Claims (1)

【特許請求の範囲】 １、ＳｉＯ＿２・Ｂ＿２Ｏ＿３・Ｎａ＿２Ｏの三成分系
からなる高硅酸多孔質ガラス微粒子であって、該微粒子
の平均直径が０．１〜３０μｍであり、かつ粒子表面に
イオン交換基を有することを特徴とする高速イオン交換
クロマトグラフィー用多孔質ガラス充填剤。 ２、上記多孔質ガラス微粒子の平均直径が１〜１０μｍ
であることを特徴とする特許請求の範囲第１項記載の高
速イオン交換クロマトグラフィー用多孔質ガラス充填剤
。 ３、上記多孔質ガラス微粒子の平均孔径が８０〜３００
０Åであることを特徴とする特許請求の範囲第１項もし
くは第２項記載の高速イオン交換クロマトグラフィー用
多孔質ガラス充填剤。 ４、上記多孔質ガラス微粒子の孔径分布（累積１０，９
０％点基準）が±１５％以内であることを特徴とする特
許請求の範囲第３項記載の高速イオン交換クロマトグラ
フィー用多孔質ガラス充填剤。 ５、上記多孔質ガラス微粒子の比表面積が１０〜２５０
ｍ＾２／ｇであることを特徴とする特許請求の範囲第１
項もしくは第２項記載の高速イオン交換クロマトグラフ
ィー用多孔質ガラス充填剤。 ６、ＳｉＯ＿２・Ｂ＿２Ｏ＿３・Ｎａ＿２Ｏの三成分系
の分相性硼硅酸ソーダガラスに熱処理を施して分相させ
た後、酸溶出処理により酸可溶性相の少なくとも一部を
溶出除去して得られる多孔質ガラス粒子を、微粉砕操作
と分級操作とにかけることによって平均直径０．１〜３
０μｍの多孔質ガラス微粒子を得て、次いで該粒子の表
面にイオン交換基を導入することを特徴とする高速イオ
ン交換クロマトグラフィー用多孔質ガラス充填剤の製造
法。 ７、多孔質ガラス微粒子の平均直径が１〜１０μｍであ
ることを特徴とする特許請求の範囲第６項記載の高速イ
オン交換クロマトグラフィー用多孔質ガラス充填剤の製
造法。 ８、上記多孔質ガラス微粒子の平均孔径が８０〜３００
０Åであることを特徴とする特許請求の範囲第６項もし
くは第７項記載の高速イオン交換クロマトグラフィー用
多孔質ガラス充填剤の製造法。 ９、上記多孔質ガラス微粒子の孔径分布（累積１０，９
０％点基準）が±１５％以内であることを特徴とする特
許請求の範囲第８項記載の高速イオン交換クロマトグラ
フィー用多孔質ガラス充填剤の製造法。 １０、上記多孔質ガラス微粒子の比表面積が１０〜２５
０ｍ＾２／ｇであることを特徴とする特許請求の範囲第
６項もしくは第７項記載の高速イオン交換クロマトグラ
フィー用多孔質ガラス充填剤の製造法。[Claims] 1. High silicic acid porous glass fine particles consisting of a three-component system of SiO_2・B_2O_3・Na_2O, which have an average diameter of 0.1 to 30 μm, and have ion exchange on the particle surface. A porous glass packing material for high performance ion exchange chromatography characterized by having a group. 2. The average diameter of the porous glass particles is 1 to 10 μm.
The porous glass packing material for high performance ion exchange chromatography according to claim 1, characterized in that: 3. The average pore diameter of the porous glass particles is 80 to 300.
The porous glass packing material for high performance ion exchange chromatography according to claim 1 or 2, characterized in that the particle size is 0 Å. 4. Pore size distribution of the above porous glass particles (cumulative 10,9
4. The porous glass packing material for high performance ion exchange chromatography according to claim 3, wherein the 0% point reference) is within ±15%. 5. The specific surface area of the porous glass particles is 10 to 250
Claim 1 characterized in that m^2/g
The porous glass packing material for high performance ion exchange chromatography according to item 1 or 2. 6. A porous material obtained by heat-treating a three-component phase-splitting sodium borosilicate glass of SiO_2, B_2O_3, and Na_2O to separate the phases, and then eluting and removing at least a portion of the acid-soluble phase using acid elution treatment. By subjecting glass particles to a fine pulverization operation and a classification operation, the average diameter is 0.1 to 3.
A method for producing a porous glass filler for high performance ion exchange chromatography, which comprises obtaining porous glass fine particles of 0 μm and then introducing an ion exchange group onto the surface of the particles. 7. The method for producing a porous glass filler for high performance ion exchange chromatography according to claim 6, wherein the porous glass particles have an average diameter of 1 to 10 μm. 8. The average pore diameter of the porous glass particles is 80 to 300.
A method for producing a porous glass filler for high performance ion exchange chromatography according to claim 6 or 7, wherein the porous glass filler has a particle diameter of 0 Å. 9. Pore size distribution of the above porous glass particles (cumulative 10,9
9. The method for producing a porous glass filler for high performance ion exchange chromatography according to claim 8, wherein the 0% point reference) is within ±15%. 10. The specific surface area of the porous glass particles is 10 to 25.
The method for producing a porous glass filler for high performance ion exchange chromatography according to claim 6 or 7, characterized in that the porous glass filler has a particle size of 0 m^2/g.
JP59226593A 1984-05-12 1984-10-27 Porous glass filler for high performance ion exchange chromatography and its preparation Granted JPS61104253A (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP59226593A JPS61104253A (en) 1984-10-27 1984-10-27 Porous glass filler for high performance ion exchange chromatography and its preparation
EP19850105871 EP0161659B1 (en) 1984-05-12 1985-05-13 Use of porous glass separation medium for high performance liquid chromatography
DE8585105871T DE3576409D1 (en) 1984-05-12 1985-05-13 USE OF A POROESE GLASS SEPARATION MEDIUM FOR HIGH-RESOLUTION LIQUID CHROMATOGRAPHY.

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP59226593A JPS61104253A (en) 1984-10-27 1984-10-27 Porous glass filler for high performance ion exchange chromatography and its preparation

Publications (2)

Publication Number Publication Date
JPS61104253A true JPS61104253A (en) 1986-05-22
JPH0572545B2 JPH0572545B2 (en) 1993-10-12

Family

ID=16847612

Family Applications (1)

Application Number Title Priority Date Filing Date
JP59226593A Granted JPS61104253A (en) 1984-05-12 1984-10-27 Porous glass filler for high performance ion exchange chromatography and its preparation

Country Status (1)

Country Link
JP (1) JPS61104253A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9580353B2 (en) 2012-10-12 2017-02-28 Asahi Glass Company, Limited Manufacturing method for phase-separated glass, and phase-separated glass

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9580353B2 (en) 2012-10-12 2017-02-28 Asahi Glass Company, Limited Manufacturing method for phase-separated glass, and phase-separated glass
US9902647B2 (en) 2012-10-12 2018-02-27 Asahi Glass Company, Limited Manufacturing method for phase-separated glass, and phase-separated glass

Also Published As

Publication number Publication date
JPH0572545B2 (en) 1993-10-12

Similar Documents

Publication Publication Date Title
KR100477291B1 (en) Process for Producing Low Density Gel Compositions
US4070286A (en) Macroporous microspheroids and a process for their manufacture
US3549524A (en) Material and method for performing steric separations
KR100609658B1 (en) Expanded perlite products with controlled particle size distribution
US2765242A (en) Process of making reinforced silica gel and esterified silica gel
CN111527047B (en) Porous silica particles and method for producing same
JPS59222224A (en) Production of surface porous macro-particle
EP0153827B2 (en) Porous particulate materials
EP1502898B1 (en) Mesoporous silica particles and production process thereof
DE10050343A1 (en) Porous silica microsphere as a cleaning agent
Mazin et al. Granulated hydroxyapatite: preparation and chromatographic properties
JPH0699135B2 (en) Manufacturing method of spherical silica gel
EP0224547B1 (en) Structured silicas
SE459731B (en) SILICAR PARTICLES, PROCEDURES FOR THEIR PREPARATION AND USE OF THE PARTICLES
US5641434A (en) Silicon nitride powder
JPS61104253A (en) Porous glass filler for high performance ion exchange chromatography and its preparation
US3233740A (en) High flow rate perlite filter aids
CN101896265A (en) Metal oxide particle and preparation method thereof and using method
JPH0414748B2 (en)
JP5771312B2 (en) Ceramic particles for chromatography filler and method for producing the same
JP2007119265A (en) Nanodiamond composition and production method therefor
EP0161659B1 (en) Use of porous glass separation medium for high performance liquid chromatography
JPS61104254A (en) Porous glass filler for high performance chromatography and its preparation
JPS6212609A (en) Modified fused spherical silica and production thereof
JPS60238758A (en) Porous glass packing material for high-speed liquid chromatography and its production