JPS63182030A - Production of porous polymer particle for adsorbing bilirubin - Google Patents
Production of porous polymer particle for adsorbing bilirubinInfo
- Publication number
- JPS63182030A JPS63182030A JP1133087A JP1133087A JPS63182030A JP S63182030 A JPS63182030 A JP S63182030A JP 1133087 A JP1133087 A JP 1133087A JP 1133087 A JP1133087 A JP 1133087A JP S63182030 A JPS63182030 A JP S63182030A
- Authority
- JP
- Japan
- Prior art keywords
- bilirubin
- polymer particles
- porous polymer
- precipitant
- particles
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 title claims abstract description 78
- 239000002245 particle Substances 0.000 title claims abstract description 47
- 229920000642 polymer Polymers 0.000 title claims abstract description 33
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims abstract description 28
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000000178 monomer Substances 0.000 claims abstract description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000012736 aqueous medium Substances 0.000 claims abstract description 6
- 238000001179 sorption measurement Methods 0.000 claims description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 12
- 238000010557 suspension polymerization reaction Methods 0.000 abstract description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 6
- 239000003463 adsorbent Substances 0.000 abstract description 5
- 238000000944 Soxhlet extraction Methods 0.000 abstract description 4
- 238000005406 washing Methods 0.000 abstract description 4
- 229910052799 carbon Inorganic materials 0.000 abstract description 3
- BODRLKRKPXBDBN-UHFFFAOYSA-N 3,5,5-Trimethyl-1-hexanol Chemical compound OCCC(C)CC(C)(C)C BODRLKRKPXBDBN-UHFFFAOYSA-N 0.000 abstract description 2
- 238000000034 method Methods 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 238000006116 polymerization reaction Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000004342 Benzoyl peroxide Substances 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 208000001940 Massive Hepatic Necrosis Diseases 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010070863 Toxicity to various agents Diseases 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000012086 standard solution Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- YIWUKEYIRIRTPP-UHFFFAOYSA-N 2-ethylhexan-1-ol Chemical compound CCCCC(CC)CO YIWUKEYIRIRTPP-UHFFFAOYSA-N 0.000 description 1
- UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 1
- WVYWICLMDOOCFB-UHFFFAOYSA-N 4-methyl-2-pentanol Chemical compound CC(C)CC(C)O WVYWICLMDOOCFB-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
- 241000219745 Lupinus Species 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000008081 blood perfusion Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- MPMBRWOOISTHJV-UHFFFAOYSA-N but-1-enylbenzene Chemical compound CCC=CC1=CC=CC=C1 MPMBRWOOISTHJV-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 239000011301 petroleum pitch Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000003505 polymerization initiator Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010558 suspension polymerization method Methods 0.000 description 1
Landscapes
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Polymerisation Methods In General (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、急性薬物中毒および劇症肝炎などの症状にお
いて、解毒代謝機能が低下することによって血液中に生
じる高濃度のビリルビンを有効に吸着除去せしめるごツ
ルビン吸着用多孔性重合体粒子の製造方法に関するもの
である。Detailed Description of the Invention [Field of Industrial Application] The present invention effectively adsorbs high concentrations of bilirubin, which is produced in the blood due to a decline in detoxification metabolic function in symptoms such as acute drug poisoning and fulminant hepatitis. The present invention relates to a method for producing porous polymer particles for adsorption of turbin.
［従来の技術およびその問題点］
薬物中毒や劇症肝炎のような症状の緊急の治療には、血
液を体外循環して直接吸着剤と接触させ、血中の高濃度
の有害物を吸着除去する直接血液潅流法（以下ＤＨＰと
称する）が有効であり、現在吸着剤として石油ピッチ系
の活性炭を利用したＤＨＰが主流となっている。しかし
ながら、活性炭においては小〜中分子量物質の吸着には
優れているが、蛋白結合ビリルビンのような高分子量物
質の吸着除去は困難であり満足すべきものではない。[Conventional technology and its problems] For emergency treatment of symptoms such as drug poisoning and fulminant hepatitis, blood is circulated extracorporeally and brought into direct contact with an adsorbent to adsorb and remove high concentrations of harmful substances from the blood. A direct blood perfusion method (hereinafter referred to as DHP) is effective, and DHP using petroleum pitch-based activated carbon as an adsorbent is currently the mainstream. However, although activated carbon is excellent in adsorbing small to medium molecular weight substances, it is difficult to adsorb and remove high molecular weight substances such as protein-bound bilirubin and is not satisfactory.
［問題を解決するための手段］
上記のような現状に鑑み、本発明者らは、優れたビリル
ビン吸着性を有するビリルビン吸着剤を製造すべく、鋭
意研究を重ねた結果、本発明を完成するに至ったもので
ある。[Means for Solving the Problem] In view of the above-mentioned current situation, the present inventors have completed the present invention as a result of extensive research in order to produce a bilirubin adsorbent having excellent bilirubin adsorption properties. This is what led to this.
すなわち、本発明のビリルビン吸着用多孔性重合体粒子
の製造方法は、ジビニルベンゼン（以下、ＤＶＢと称す
る）３５〜１００重量％とグリシジルメタクリレート（
以下、ＧＭＡと称する）Ｏ〜６５重量％の混合上ツマ−
を、炭素原子数５〜１２の一価アルコールを沈殿剤とし
て水性媒体中で懸濁重合せしめることを特徴とするもの
であり、懸濁重合によって得られた多孔性重合体粒子は
、適宜の精製工程、例えば初めに水、次いでメタノール
で洗浄し、更にアセトンで恒量になるまでソックスレー
抽出し、粒子中に残存している沈殿剤および七ツマ−を
除去する工程を経て、吸着用多孔性重合体粒子とするこ
とができる。That is, the method for producing porous polymer particles for adsorbing bilirubin of the present invention includes 35 to 100% by weight of divinylbenzene (hereinafter referred to as DVB) and glycidyl methacrylate (
(hereinafter referred to as GMA)
is characterized by suspension polymerization in an aqueous medium using a monohydric alcohol having 5 to 12 carbon atoms as a precipitant, and the porous polymer particles obtained by suspension polymerization are subjected to appropriate purification. After a process, for example, first washing with water and then methanol, and further Soxhlet extraction with acetone to a constant weight to remove the precipitant and sulfuric acid remaining in the particles, the porous polymer for adsorption is prepared. It can be a particle.
本発明でいう沈殿剤とは、「モノマーとは完全に相溶す
るが、重合により生成したポリマーには親和性を示さな
い溶媒」を意味し、該溶媒の共存下でモノマーを懸濁重
合すると、その多くは直径１μｍ以下の著しく微細なポ
リマー−次粒子を生成し、これが凝集体となって、一般
にマクロレティキュラー型多孔性樹脂と呼ばれる多孔性
重合体を形成する。The precipitant as used in the present invention means a "solvent that is completely compatible with the monomer but has no affinity for the polymer produced by polymerization", and when monomers are suspended in the coexistence of the solvent, Most of them produce extremely fine secondary polymer particles with a diameter of 1 μm or less, which aggregate to form a porous polymer generally called a macroreticular porous resin.
本発明において、ＤＶＢ／ＧＭＡの混合比率はＤＶＢ
（重量％）／ＧＭＡ（重量％）−３５〜１００１０〜６
５の範囲であることが必要であり、６５〜９５１５〜３
５の範囲であることが好ましい。ＤＶＢの混合比率が３
５重量％未満であると、得られる多孔性重合体粒子はビ
リルビン吸着に適した多孔化とならず、吸着量が著しく
減少するため好ましくない。In the present invention, the DVB/GMA mixing ratio is DVB/GMA.
(wt%)/GMA (wt%) -35~10010~6
Must be in the range of 5, 65-9515-3
It is preferable that it is in the range of 5. DVB mix ratio is 3
If it is less than 5% by weight, the resulting porous polymer particles will not have pores suitable for bilirubin adsorption, and the amount of adsorption will significantly decrease, which is not preferable.
本発明に用いることのできるＤＶＢとしては、高純度な
りＶＢはもちろんのことでおるが、一般に工業用として
供給されている工業用ＤＶＢ （エチルビニルベンゼン
およびその他の種々の飽和化合物との混合物を含み、Ｄ
ＶＢｔｉ！度約５５重量％）も本発明において好ましく
用いることができる。The DVB that can be used in the present invention includes not only high-purity VB, but also industrial DVB that is generally supplied for industrial use (including mixtures with ethylvinylbenzene and various other saturated compounds). ,D
VBti! about 55% by weight) can also be preferably used in the present invention.
なお、工業用ＤＶＢを用いる場合のＧＭＡとの混合モノ
マー比は、含有するＤＶＢＩが上記混合比率の範囲とな
るようにするのが好ましい。In addition, when using industrial DVB, it is preferable that the mixed monomer ratio with GMA is such that the DVBI contained falls within the above mixing ratio range.
上記ＤＶＢ／ＧＭＡ系多孔性重合体の多孔化に際して用
いることのできる沈殿剤としては、炭素原子数５〜１２
の一価アルコールであり、炭素原子数５未満の一価アル
コールは水に対する溶解性が大きく（たとえば炭素原子
数４のｎ−ブタノールは水１００ｍＩ中に３０℃で７．
７ｇ溶解する）懸濁重合の際分散媒水相中へ溶解し、七
ツマー相中のアルコール量が減少して目的とする多孔化
とならず、また炭素原子数１２より大のアルコール（た
とえばテトラデカノールなど）はＤＶＢ／ＧＭＡモノマ
ーへの溶解性が劣るため均一な多孔化が得られなかった
り、粒子強度が低下したりすることがおるので好ましく
ない。したがって、本発明においては、炭素原子数８〜
９の一価アルコールが特に好ましく用いることができる
。The precipitant that can be used to make the above DVB/GMA porous polymer porous has 5 to 12 carbon atoms.
Monohydric alcohols with less than 5 carbon atoms have a high solubility in water (for example, n-butanol with 4 carbon atoms has a 7.
During suspension polymerization, the amount of alcohol in the hexamer phase decreases and the desired porosity cannot be achieved, and alcohols with a carbon number greater than 12 (e.g. Decanol, etc.) is not preferred because it has poor solubility in the DVB/GMA monomer and may not provide uniform porosity or may reduce particle strength. Therefore, in the present invention, the number of carbon atoms is 8 to
The monohydric alcohol No. 9 can be particularly preferably used.
なお、炭素原子数５の一価アルコールでも、水に対する
溶解度の大きなアルコール（たとえばｔｅｒ、−アミル
アルコールは水１００ｍＪ！中３０°Ｃで１４３溶解す
る）は、炭素原子数４未満の一価アルコールと同様に目
的とする多孔化が得られないことがあるので、−価アル
コールとしては、炭素原子数が上記特定範囲である上に
、水に対する溶解度（水１００ｒｒｌ中３０℃における
溶解９数）が、７以下、好ましくは５以下、特に好まし
くは３以下であることが、なおざらに好ましい。Even monohydric alcohols with 5 carbon atoms have high solubility in water (for example, ter, -amyl alcohol dissolves at 30°C in 100 mJ of water), and monohydric alcohols with less than 4 carbon atoms have high solubility in water. Similarly, since the desired porosity may not be obtained, the -hydric alcohol should have a carbon atom number within the above specified range and a water solubility (dissolution of 9 at 30°C in 100 rrl of water). It is even more preferred that it be 7 or less, preferably 5 or less, particularly preferably 3 or less.
本発明において用いることのできる沈殿剤の具体例とし
ては、ｎ−アミルアルコール、ｎ−オクチルアルコール
、４−メチル−２−ペンタノール、３．５．５−トリメ
チルヘキサノール、ラウリルアルコール、２−エチルヘ
キシルアルコール、ジ。Specific examples of precipitants that can be used in the present invention include n-amyl alcohol, n-octyl alcohol, 4-methyl-2-pentanol, 3.5.5-trimethylhexanol, lauryl alcohol, and 2-ethylhexyl alcohol. , Ji.
イソブチルカルビノールなどであり、特に炭素原子数８
〜９のｎ−オクチルアルコール、３，５゜５−トリメチ
ルヘキサノールなどが好ましい。Isobutyl carbinol, etc., especially those with 8 carbon atoms
-9 n-octyl alcohol, 3,5°5-trimethylhexanol and the like are preferred.
本発明において、ビリルビン吸着用多孔性重合体粒子は
、上記モノマーに沈殿剤を存在させ、水性媒体中で懸濁
重合することによって製造することができるが、用いる
沈殿剤の量は、ＤＶＢ／ＧＭＡ系七ツマ−１００重量部
に対し、６５〜１８０重量部、特に８０〜１５０重量部
が好ましい。In the present invention, the porous polymer particles for adsorbing bilirubin can be produced by adding a precipitant to the monomer and carrying out suspension polymerization in an aqueous medium. It is preferably 65 to 180 parts by weight, particularly 80 to 150 parts by weight, per 100 parts by weight of the seven-spotted salt.
沈殿剤が６５重量部より少ないとビリルビン吸着剤とし
て好適な多孔化が得られなくなり、１８０重量部より多
くなると、多孔化が過度となり、強度の小さな粒子とな
るので好ましくない。また、懸濁重合法は、それ自体特
殊なものではなく、従来公知の方法で行うことができる
。なお、本懸濁重合において、水性媒体中へ少量のＮａ
Ｃｌを加えておくと、ＧＭＡの水相への溶出によって生
成されるエマルジョン粒子で多孔粒の表面が汚染される
という欠点が低減され、得られた多孔粒の分離および精
製が容易におこなえる利点がある。また、重合温度を段
階的に昇温すると、初めから高温で反応させた場合に比
較して重合時間は長くなるが、得られた重合体粒子に残
存するストレスが低減され、粒子表面に発生する亀裂の
防止にプラスの働きをする。しかしながら、これら２つ
の手法は、本発明にとって必須の要件を構成するもので
はない。生成した重合体粒子は、適宜な精製方法、たと
えば、初めに水、次いでメタノールで洗浄し、さらにア
セトンで恒量になるまでソックスレー抽出し、粒子中に
残存している沈殿剤およびモノマーを除去することによ
り、多孔性重合体粒子を得ることができる。If the amount of the precipitant is less than 65 parts by weight, suitable porosity as a bilirubin adsorbent cannot be obtained, and if it is more than 180 parts by weight, the porosity becomes excessive, resulting in particles with low strength, which is not preferable. Further, the suspension polymerization method itself is not special, and can be carried out by conventionally known methods. In addition, in this suspension polymerization, a small amount of Na is added to the aqueous medium.
Adding Cl reduces the disadvantage that the surface of the porous particles is contaminated with emulsion particles generated by elution of GMA into the aqueous phase, and has the advantage that the resulting porous particles can be easily separated and purified. be. In addition, when the polymerization temperature is raised stepwise, the polymerization time becomes longer than when the reaction is carried out at a high temperature from the beginning, but the stress remaining in the obtained polymer particles is reduced, and the stress generated on the particle surface is reduced. It has a positive effect on preventing cracks. However, these two techniques do not constitute essential requirements for the present invention. The resulting polymer particles may be purified using a suitable purification method, such as first washing with water and then methanol, and further Soxhlet extraction with acetone to constant weight to remove any precipitants and monomers remaining in the particles. By this method, porous polymer particles can be obtained.
以上のようにして得られた本発明多孔性重合体粒子はビ
リルビン吸着用途に好ましく用いることができ、特に高
濃度ごプルビン代謝異常患者のビリルビン吸着に効果的
に用いることができる。The porous polymer particles of the present invention obtained as described above can be preferably used for adsorbing bilirubin, and can be particularly effectively used for adsorbing bilirubin in patients with high-concentration pulvin metabolic disorders.
［実施例］
本発明を以下の実施例に基づいて、ざらに詳細に説明す
る。[Examples] The present invention will be roughly described in detail based on the following examples.
実施例１゜
ウォーターバスに設置した撹拌翼およびコンデンサー付
きのＩＮのせパラプルフラスコに、イオン交換水４５０
９を仕込み、撹拌下（１４０〜１６０ｒｐｍ＞で分散剤
［ポリビニルアルコール（日本合成化学工業社製、ゴー
セノールＧＨ−２３）６％水溶液］７．５ｇとＮａＣ＋
１８９を加えて溶解させ、水相を形成させた。これに、
ＤＶＢ （ＤＶＢ含有率５５％（７）工業用ＤＶＢ）２
４ｙおよびＧＭＡ６７のモノマー混合物、沈殿剤（３゜
５．５−トリメチルヘキサノール’）３０’ｊｊ１３よ
び重合開始剤（ＢＰＯ：ベンゾイルパーオキサイド）０
．３７を加えて混合溶解した油相を同じく撹拌下で加え
、外温を６０℃から９０℃に段階的に昇温しつつ、７時
間かけて重合反応をおこなった。Example 1゜450 ion-exchanged water was added to an IN paraple flask equipped with a stirring blade and a condenser installed in a water bath.
9, and while stirring (140-160 rpm), add 7.5 g of dispersant [6% aqueous solution of polyvinyl alcohol (manufactured by Nippon Gosei Kagaku Kogyo Co., Ltd., Gohsenol GH-23)] and NaC +
189 was added and dissolved to form an aqueous phase. to this,
DVB (DVB content 55% (7) industrial DVB) 2
Monomer mixture of 4y and GMA67, precipitant (3°5.5-trimethylhexanol') 30'jj13 and polymerization initiator (BPO: benzoyl peroxide) 0
．． The oil phase in which 37 was added and mixed and dissolved was added under stirring, and the polymerization reaction was carried out over 7 hours while the external temperature was raised stepwise from 60°C to 90°C.
反応液は１００メツシユの篩で濾過し、得られた重合体
粒子は初めに水、次いでメタノールで充分に洗浄し、ざ
らにアセトンにより恒量になるまでソックスレー抽出を
おこなって精製し、風乾してビリルビン吸着用多孔性重
合体粒子とした。The reaction solution was filtered through a 100-mesh sieve, and the resulting polymer particles were first thoroughly washed with water and then methanol, purified by Soxhlet extraction with acetone until a constant weight, and air-dried to obtain bilirubin. Porous polymer particles for adsorption were used.
上記で得られた多孔性重合体粒子について、ビリルビン
吸着率を下記の方法で測定したところ、９０．３％でお
り、極めて優れた性能のものであった。When the bilirubin adsorption rate of the porous polymer particles obtained above was measured by the method described below, it was 90.3%, which was an extremely excellent performance.
ビリルビン吸着率測定法；下記（ａ）〜（Ｃ）の手順で
ビリルビン吸着率を測定する。Bilirubin adsorption rate measurement method: The bilirubin adsorption rate is measured according to the following procedures (a) to (C).
（ａ＞高ヒ刀ルピン値模擬血清の作成
ビリルビン１５ｍｇにジメチルスルホキシド１．０ｍ、
Ｉｌ 、０．１Ｍ炭酸ナトリウム２．０ｍｇを加え溶解
し、これに、０．−１３４Ｍリン酸緩衡液（ｐＨ７，４
＞を用いて調製したアルブミン標準液（５，５９／ｄＮ
）を加えて、ｐＨ７，４に調整して、ビリルビン標準
液（１５ｍｙ／ｄＵ ）を調製する。(a> Preparation of serum simulating high lupine level 15 mg of bilirubin, 1.0 m of dimethyl sulfoxide,
Add and dissolve 2.0 mg of 0.1M sodium carbonate, and to this, 0.1M sodium carbonate is added and dissolved. -134M phosphate buffer (pH 7.4
>Albumin standard solution (5,59/dN
) and adjust the pH to 7.4 to prepare a bilirubin standard solution (15 my/dU).
（ｂ）多孔性粒子の親水処理
乾燥した多孔粒は水との親和性に乏しく、水溶液中に浸
漬しても、細孔中の空気と水溶液の置換が起こり難いた
め、初めにエタノール中に多孔粒を入れ、脱気後、水で
充分に洗い流し、０．１３４Ｍリン酸緩衡液（ｐＨ７，
４＞に−夜浸漬する。(b) Hydrophilic treatment of porous particles Dried porous particles have poor affinity with water, and even when immersed in an aqueous solution, it is difficult to replace the air in the pores with the aqueous solution. After adding the grains and degassing, rinse thoroughly with water and add 0.134M phosphoric acid buffer (pH 7,
4> - Soak overnight.
（Ｃ）ビリルビン吸着率の測定
上記（ａ）の模擬血清５ｍｇに、（ｂ）の多孔性粒子（
乾燥時重量で＞０．１！Ｊを加え、３７℃で２時間振盪
して血清中のビリルビンを多孔性重合体粒子に吸着させ
る。次いで多孔性粒子を濾過し、濾液をフルカリアゾビ
リルビン法に基づくビリルビン測定用試薬（和光紬薬工
業社製、Ｂ１１１ｒｕｂｉｎ ＢＩＩ−ＴｅｓｔＷａ
ＫＯ＞を用いて発色させ、６００ｎｍの波長における吸
光度を測定し、この値をサンプル値とする。(C) Measurement of bilirubin adsorption rate 5 mg of the simulated serum of (a) above was added to the porous particles of (b) (
Dry weight >0.1! J and shaken at 37°C for 2 hours to allow bilirubin in the serum to be adsorbed onto the porous polymer particles. Next, the porous particles were filtered, and the filtrate was mixed with a reagent for measuring bilirubin based on the flucariazobilirubin method (manufactured by Wako Tsumugi Kogyo Co., Ltd., B111rubin BII-TestWa).
KO> is used to develop color, the absorbance at a wavelength of 600 nm is measured, and this value is used as the sample value.
別に上記（ｂ）の多孔性粒子を加えないで、（ａ）の模
擬血清のみで前記同様に処理して吸光度を測定しくコン
トロール値という）、次式によりビルビリン吸着率（％
）を算出する。Separately, without adding the porous particles of (b) above, treat with only the simulated serum of (a) in the same manner as above and measure the absorbance (referred to as the control value).
) is calculated.
ビリルビン吸着率（％）一
実施例２〜４および比較例１．２
実施例１同様に下記表−１に示したそれぞれの配合組成
（重量部を示す）で、沈殿剤の異なる多孔性重合体粒子
を製造し、同様にビリルビン吸着率を測定した。その結
果を合わせて表−１に示した。Bilirubin adsorption rate (%) - Examples 2 to 4 and Comparative Examples 1.2 Similar to Example 1, porous polymers with different precipitants were prepared with the respective formulations (parts by weight) shown in Table 1 below. Particles were produced and the bilirubin adsorption rate was measured in the same manner. The results are shown in Table 1.
（以下余白）
上記表−１の結果から明らかなように本発明方法で製造
した実施例２〜実施例４の多孔性重合体粒子は、優れた
ビリルビン吸着特性を示す粒子であった。これに対し、
比較例１に示した沈殿剤（ｎ−１タノール）は、水に対
する溶解度が７゜７（３０℃）と大きなため、ビリルビ
ン吸着に適する多孔化をとらず、ビリルビン吸着率は、
極めて低い値となった。また、比較例２に示した沈殿剤
（テトラデカノール）はモノマーに対する溶解度が小さ
く、均一の多孔化が起こらないため、ビリルビン吸着率
は低い値となった。(The following is a blank space) As is clear from the results in Table 1 above, the porous polymer particles of Examples 2 to 4 produced by the method of the present invention were particles that exhibited excellent bilirubin adsorption properties. In contrast,
The precipitant (n-1 tanol) shown in Comparative Example 1 has a high solubility in water of 7°7 (30°C), so it does not have porosity suitable for bilirubin adsorption, and the bilirubin adsorption rate is
This was an extremely low value. Furthermore, the precipitant (tetradecanol) shown in Comparative Example 2 had low solubility in monomers and did not produce uniform porosity, resulting in a low bilirubin adsorption rate.
実施例５〜８および比較例３
下記表−２に示したそれぞれの配合組成（重量部を示す
）にしたがって、ＤＶＢ／ＧＭＡ比の異なる多孔性重合
体粒子を実施例１と同様の方法で製造し、ビリルビン吸
着率を測定した。その結果を合わせて表−２に示した。Examples 5 to 8 and Comparative Example 3 Porous polymer particles with different DVB/GMA ratios were produced in the same manner as in Example 1 according to the respective compounding compositions (parts by weight shown) shown in Table 2 below. Then, the bilirubin adsorption rate was measured. The results are shown in Table 2.
（以下余白）
上記表−２の結果から明らかなように、本発明方法で製
造した実施例５〜８の多孔性重合体粒子は、優れたビリ
ルビン吸着特性を示す粒子でおった。これに対し、比較
例３の粒子は、ＤＶＢ／ＧＭＡ比が２６．８／７３．２
で、ＧＭＡの含有量が本発明の範囲を越えて多いため、
親水性が高くなるとともに、ビリルビン吸着に適した多
孔化とならず、ビリルビン吸着率は低い値となった。(The following is a blank space) As is clear from the results in Table 2 above, the porous polymer particles of Examples 5 to 8 produced by the method of the present invention were particles that exhibited excellent bilirubin adsorption properties. On the other hand, the particles of Comparative Example 3 had a DVB/GMA ratio of 26.8/73.2.
However, since the content of GMA is higher than the scope of the present invention,
As the hydrophilicity increased, the porosity did not become suitable for bilirubin adsorption, and the bilirubin adsorption rate became a low value.
実施例９〜１２
下記表−３に示したそれぞれの配合組成（重量部を示す
）にしたがって、（ＤＶＢ十〇ＭＡ）／沈殿剤（３，５
，５−トリメチルヘキサノール）比を変えた多孔性重合
体粒子を実施例１と同様の方法で製造し、ビリルビン吸
着率を測定した。Examples 9 to 12 (DVB 100 MA)/precipitant (3,5
, 5-trimethylhexanol) were produced in the same manner as in Example 1, and the bilirubin adsorption rates were measured.
その結果を合わせて表−３に示した。The results are shown in Table 3.
（以下余白）
上記表−３の結果からも明らかなように、本発明方法で
製造した実施例９〜１２の多孔性重合体粒子は優れたビ
リルビン吸着特性を示す粒子であった。特に（ＤＶＢ＋
ＧＭＡ）／沈殿剤比が１００／８０〜１００／１５０の
範囲で製造した実施例１０〜１２の粒子は、ビリルビン
吸着用担体として適する多孔化構造を形成し、特に優れ
たビリルビン吸着特性の得られることが認められた。(Here are blank spaces) As is clear from the results in Table 3 above, the porous polymer particles of Examples 9 to 12 produced by the method of the present invention were particles that exhibited excellent bilirubin adsorption properties. Especially (DVB+
The particles of Examples 10 to 12 produced with a GMA)/precipitating agent ratio in the range of 100/80 to 100/150 formed a porous structure suitable as a carrier for bilirubin adsorption, and exhibited particularly excellent bilirubin adsorption properties. This was recognized.
［発明の効果］
本発明のビリルビン吸着用多孔性重合体粒子の製造方法
は、炭素原子数５〜１２の一価アルコールを沈殿剤とし
て、ＤＶＢないしＤＶＢとＧＭＡの懸濁重合によって製
造することからなっているので、蛋白結合ビリルビンの
吸着性能に優れた巨大多孔化構造の重合体粒子を形成す
ることができ、特に高濃度ビリルビンの吸着のための多
孔性重合体粒子を容易に製造する方法として極めて優れ
たものである。[Effects of the Invention] The method for producing porous polymer particles for adsorbing bilirubin of the present invention involves producing them by suspension polymerization of DVB or DVB and GMA using a monohydric alcohol having 5 to 12 carbon atoms as a precipitant. As a result, it is possible to form polymer particles with a giant porous structure that has excellent adsorption performance for protein-bound bilirubin.This method is particularly useful as a method for easily producing porous polymer particles for adsorption of high-concentration bilirubin. It is extremely excellent.
Claims (2)
ルメタクリレート０〜６５重量％の混合モノマーを、炭
素原子数５〜１２の一価アルコールを沈殿剤として水性
媒体中で懸濁重合せしめることを特徴とするビリルビン
吸着用多孔性重合体粒子の製造方法。(1) A monomer mixture of 35 to 100% by weight of divinylbenzene and 0 to 65% by weight of glycidyl methacrylate is suspension-polymerized in an aqueous medium using a monohydric alcohol having 5 to 12 carbon atoms as a precipitant. A method for producing porous polymer particles for bilirubin adsorption.
重量％およびグリシジルメタクリレート５〜３５重量％
の混合比である特許請求の範囲第１項に記載の多孔性重
合体粒子の製造方法。(2) The mixed monomer is divinylbenzene 65-95
wt% and glycidyl methacrylate 5-35 wt%
The method for producing porous polymer particles according to claim 1, wherein the mixing ratio is:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1133087A JPH0724771B2 (en) | 1987-01-22 | 1987-01-22 | Process for producing porous polymer particles for bilirubin adsorption |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1133087A JPH0724771B2 (en) | 1987-01-22 | 1987-01-22 | Process for producing porous polymer particles for bilirubin adsorption |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63182030A true JPS63182030A (en) | 1988-07-27 |
| JPH0724771B2 JPH0724771B2 (en) | 1995-03-22 |
Family
ID=11775019
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1133087A Expired - Lifetime JPH0724771B2 (en) | 1987-01-22 | 1987-01-22 | Process for producing porous polymer particles for bilirubin adsorption |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0724771B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103159891A (en) * | 2013-03-28 | 2013-06-19 | 南京大学 | Magnetic amino-modified superhighly-crosslinked resin and preparation method thereof |
-
1987
- 1987-01-22 JP JP1133087A patent/JPH0724771B2/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103159891A (en) * | 2013-03-28 | 2013-06-19 | 南京大学 | Magnetic amino-modified superhighly-crosslinked resin and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0724771B2 (en) | 1995-03-22 |
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