JPS62191041A - Adsorbent of activated complementary component and removal of said component - Google Patents
Adsorbent of activated complementary component and removal of said componentInfo
- Publication number
- JPS62191041A JPS62191041A JP61005535A JP553586A JPS62191041A JP S62191041 A JPS62191041 A JP S62191041A JP 61005535 A JP61005535 A JP 61005535A JP 553586 A JP553586 A JP 553586A JP S62191041 A JPS62191041 A JP S62191041A
- Authority
- JP
- Japan
- Prior art keywords
- adsorbent
- functional group
- anionic functional
- activated
- water
- 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
- 230000000295 complement effect Effects 0.000 title claims abstract description 32
- 239000003463 adsorbent Substances 0.000 title claims abstract description 29
- 125000000524 functional group Chemical group 0.000 claims abstract description 25
- 125000000129 anionic group Chemical group 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 12
- 210000001124 body fluid Anatomy 0.000 claims description 6
- 239000010839 body fluid Substances 0.000 claims description 6
- 239000011148 porous material Substances 0.000 claims description 5
- -1 sulfate ester compound Chemical class 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 abstract description 6
- 230000008105 immune reaction Effects 0.000 abstract description 4
- 238000000502 dialysis Methods 0.000 abstract description 3
- 229920000936 Agarose Polymers 0.000 abstract description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 2
- 125000004185 ester group Chemical group 0.000 abstract description 2
- 239000012634 fragment Substances 0.000 abstract description 2
- 239000000178 monomer Substances 0.000 abstract description 2
- 230000000379 polymerizing effect Effects 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 abstract 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 abstract 1
- 210000004072 lung Anatomy 0.000 abstract 1
- 230000000638 stimulation Effects 0.000 abstract 1
- 239000000499 gel Substances 0.000 description 16
- 210000002381 plasma Anatomy 0.000 description 10
- 239000000243 solution Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 5
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229920002125 Sokalan® Polymers 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000004154 complement system Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000004584 polyacrylic acid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 229920003045 dextran sodium sulfate Polymers 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000003100 immobilizing effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- CHRJZRDFSQHIFI-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;styrene Chemical compound C=CC1=CC=CC=C1.C=CC1=CC=CC=C1C=C CHRJZRDFSQHIFI-UHFFFAOYSA-N 0.000 description 1
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 229920002567 Chondroitin Polymers 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 1
- 229920000805 Polyaspartic acid Polymers 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 102000034238 globular proteins Human genes 0.000 description 1
- 108091005896 globular proteins Proteins 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 210000004880 lymph fluid Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000002616 plasmapheresis Methods 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920000172 poly(styrenesulfonic acid) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000447 polyanionic polymer Polymers 0.000 description 1
- 108010064470 polyaspartate Proteins 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229940005642 polystyrene sulfonic acid Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000005373 porous glass Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000005372 silanol group Chemical group 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical group S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000000352 supercritical drying Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- External Artificial Organs (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野コ
本発明は活性化された補体成分を含む溶液より活性化補
体成分を吸着除去するための吸上体およびそれを用いた
活性化補体成分の除去方法に関する。Detailed Description of the Invention [Industrial Field of Application] The present invention relates to an wicking body for adsorbing and removing activated complement components from a solution containing activated complement components, and an activated complement using the same. Relating to a method for removing body components.
さらに詳しくは体液中より活性化された補体成分を除去
し、過剰な免疫反応を抑制するための吸着体およびそれ
を用いた活性化補体成分の除去方法に関する。More specifically, the present invention relates to an adsorbent for removing activated complement components from body fluids and suppressing excessive immune reactions, and a method for removing activated complement components using the adsorbent.
［従来の技術および発明が解決しようとする問題点］
生体の免疫反応の一環として補体系の反応があり、液性
免疫系の一つの重要な機能を担っている。しかしながら
時として補体系の過剰な活性化は過剰な炎症反応などを
引き起こし、生体を危険な状態に陥れることがある。と
くに主要臓器の炎症、腫瘍などにおいては活性化された
補体成分がさらに重篤な免疫反応を引き起こし、基礎疾
忌の治療をより困■にするばかりでなく、生体そのもの
を死に至らしめることすらある。[Prior Art and Problems to be Solved by the Invention] Complement system reactions are part of the immune reactions of living bodies, and play an important role in the humoral immune system. However, excessive activation of the complement system sometimes causes excessive inflammatory reactions and puts the body in a dangerous state. In particular, in cases of inflammation in major organs, tumors, etc., activated complement components cause even more severe immune reactions, which not only makes it more difficult to treat the underlying disease, but can even lead to the death of the organism itself. be.
さらに人工透析、人工心肺、血漿交換などの体外循環治
療あるいはその他の人工臓器使用時の補体系の活性化に
よるアナフィラキシ−が問題視されている。Furthermore, anaphylaxis due to activation of the complement system during extracorporeal circulation treatments such as artificial dialysis, artificial heart-lung therapy, and plasma exchange, or when using other artificial organs, is considered a problem.
これらの活性化補体成分による障害を予防し、中和する
目的で種々の抗炎症剤が開発され使用されているが、必
ずしも満足しつる効果をあげている訳ではなく、とくに
急性反応期においてはその効果は不充分であり、活性化
補体成分の急速な除去方法の開発が望まれている。Various anti-inflammatory drugs have been developed and used to prevent and neutralize the damage caused by these activated complement components, but they do not always have a satisfactory effect, especially in the acute reaction phase. However, the effect is insufficient, and it is desired to develop a method for rapid removal of activated complement components.
本発明は前記のごとき問題点を解決するためになされた
ものである。The present invention has been made to solve the above problems.
［問題点を解決（るための手段］
本発明はアニオン性官能基を有する吸着体およびこれに
活性化補体成分を含む溶液を接触させることによる活性
化神体成分の除去方法に関する。[Means for Solving the Problems] The present invention relates to an adsorbent having an anionic functional group and a method for removing an activated complement component by contacting the adsorbent with a solution containing an activated complement component.
［実施例］
本明細書でいう活性化補体成分とは、抗原−抗体反応そ
の他の刺激により生じるＣ２ｂ、Ｃ３８、Ｃ３ｂ、Ｃ３
ｄ１Ｃ４８、Ｃ５ａ、Ｃ５ｂなどの補体の活性化フラグ
メントおよびＣ１、Ｃ４ｂ２ａ、Ｃ４ｂ２ａ３ａ、Ｃ３
ｂＢなどの活性化補体複合体を指す。[Example] Activated complement components as used herein refer to C2b, C38, C3b, and C3 generated by antigen-antibody reactions and other stimuli.
Activation fragments of complement such as d1C48, C5a, C5b and C1, C4b2a, C4b2a3a, C3
Refers to activated complement complexes such as bB.
さらに木用ｍ１１でいう体液とは生体内に存在する液性
成分を指し、血液、血清、血漿、リンパ液、腹水などを
例としてあげることができる。Furthermore, body fluids as used in the wooden m11 refer to humoral components existing in living bodies, and include blood, serum, plasma, lymph fluid, ascites, and the like.
木用Ｉｌｌ麿に用いるアニオン性官能基は、ＩＩＨが中
性付近で負に荷電するような官能基であればいかなるも
のをも使用しうる。これらの代表例としては、カルボキ
シル
エステル基、シラノール基、リン酸エステル基、フェノ
ール性水酸基などがあげられるが、これらのみに限定さ
れるものではない。As the anionic functional group used in Illmaro for wood, any functional group can be used as long as IIH is negatively charged near neutrality. Typical examples of these include carboxyl ester groups, silanol groups, phosphate ester groups, and phenolic hydroxyl groups, but are not limited to these.
これらのアニオン性官能基の吸着体への導入方法は種々
あり、いかなる方法で導入してもよいが、代表的な導入
方法としては
（１）アニオン性官能基含有モノマーを重合して吸着体
を形成させる方法、
（２）アニオン性官能基含有化合物を水不溶性担体に固
定させる方法、
（３）アニオン性官能基を形成する化合物と水不溶性担
体を直接反応させる方法
などがあげられる。もちろんガラス、シリカ、アルミナ
などもともとアニオン性官能基を含有づるアニオン性官
能基含有化合物を吸着体として用いてもよい。There are various ways to introduce these anionic functional groups into the adsorbent, and any method may be used. Typical introduction methods include (1) polymerizing an anionic functional group-containing monomer to form an adsorbent; (2) a method of immobilizing an anionic functional group-containing compound to a water-insoluble carrier; and (3) a method of directly reacting a compound that forms an anionic functional group with a water-insoluble carrier. Of course, an anionic functional group-containing compound such as glass, silica, alumina, etc. that inherently contains an anionic functional group may be used as the adsorbent.
またアニオン性官能基含有化合物を水不溶性担体に固定
させる方法により、アニオン性官能基を吸着体に導入づ
るばあいには、用いる化合物はアニオン性官能基を１つ
、有するものでもよく、また多聞のアニオン性官能基を
導入しゃずいという点から２つ以上有するポリアニオン
化合物でもよい。In addition, when an anionic functional group is introduced into an adsorbent by a method of immobilizing an anionic functional group-containing compound on a water-insoluble carrier, the compound used may have one anionic functional group; A polyanionic compound having two or more anionic functional groups may also be used in order to prevent the introduction of anionic functional groups.
前記ポリアニオン化合物の代表例としてはポリアクリル
酸、ポリビニルスルホン酸、ポリビニル酸、ポリスチレ
ンスルホン酸、ポリスチレンリン酸、ポリグルタミン酸
、ポリアスパラギン酸、ポリメタクリル酸、ポリリン酸
、スチレン−マレイン酸共重合体などの合成ポリアニオ
ン、さらにヘパリン、デキストラン硫酸、コンドロイチ
ン、コンドロイチン硫酸、キチン、キトサンなどのアニ
オン性官能基含有多糖類があげられるが、これらのみに
限定されるものではない。Representative examples of the polyanionic compounds include polyacrylic acid, polyvinylsulfonic acid, polyvinyl acid, polystyrene sulfonic acid, polystyrene phosphoric acid, polyglutamic acid, polyaspartic acid, polymethacrylic acid, polyphosphoric acid, and styrene-maleic acid copolymer. Examples include, but are not limited to, synthetic polyanions and anionic functional group-containing polysaccharides such as heparin, dextran sulfate, chondroitin, chondroitin sulfate, chitin, and chitosan.
本発明に用いる水不溶性担体はいかなるものをも使用し
うるが、吸着表面積を大きくするためには多孔質体であ
るのが好ましい。Although any water-insoluble carrier can be used in the present invention, a porous carrier is preferable in order to increase the adsorption surface area.
本発明に用いる水不溶性多孔質物質の代表例としては、
アガロース、デキストラン、ポリアクリルアミドなどの
軟質ゲル、多孔質ガラス、多孔質シリカゲルなどの無機
多孔体、ポリメチルメタクリレート、ポリビニルアルコ
ール、スチレン−ジビニルベンゼン共組合体などの合成
高分子化合物、セルロースなどの天然高分子化合物を原
料とする多孔質ポリマーハードゲルなどがあげられるが
、これらのみに限定されるものではない。Representative examples of water-insoluble porous materials used in the present invention include:
Soft gels such as agarose, dextran, and polyacrylamide; inorganic porous materials such as porous glass and porous silica gel; synthetic polymers such as polymethyl methacrylate, polyvinyl alcohol, and styrene-divinylbenzene co-operative; and natural polymers such as cellulose. Examples include, but are not limited to, porous polymer hard gels made from molecular compounds.
これらの水不溶性多孔質物質のなかでも体外循環治療に
用いるためには粘性の高い体液を流しても変形による圧
力損失の増加、詰まりなどが生じない硬質ゲルを用いる
のがより好ましいが、さらには担体自身による補体の活
性化が少ない担体を用いるのがより一層好ましい。Among these water-insoluble porous materials, for use in extracorporeal circulation therapy, it is more preferable to use hard gels that do not cause increased pressure loss or clogging due to deformation even when flowing highly viscous body fluids; It is even more preferable to use a carrier that is less likely to activate complement by itself.
活性化補体成分を含む溶液を本発明による吸着体と接触
させることにより該溶液より活性化補体成分を除去する
ことができる。活性化補体成分を含む溶液と吸着体とを
接触させる方法としてはいかなる方法をも採用しうるが
、体外循環により体液中の活性化補体成分を取り除くば
あいには、該吸着体を体液の入口と出口を有する容器に
充填し、体外循環回路に組み込んで該容器に体液を流通
させる方法が安全性、除去効率の面で好ましい。Activated complement components can be removed from a solution containing activated complement components by contacting the solution with an adsorbent according to the invention. Any method can be used to bring the adsorbent into contact with a solution containing activated complement components, but when removing activated complement components from body fluids by extracorporeal circulation, the adsorbent may be brought into contact with the adsorbent. In terms of safety and removal efficiency, it is preferable to fill a container with an inlet and an outlet, incorporate it into an extracorporeal circulation circuit, and circulate the body fluid through the container.
以下に実施例に基づいて本発明の活性化補体成分の吸上
体おＪ、び除去方法をさらに詳細に説明するが、本発明
はかかる実施例のみに限定されるものではない。The wicking body and method for removing activated complement components of the present invention will be described in more detail below based on Examples, but the present invention is not limited to these Examples.
実施例１
架橋ポリアクリレートゲル（全多孔性のハードゲル）で
あるトヨバール＋１）１６５（東洋１１ル製＞ １０ｍ
に飽和ＮａＯＨ水溶液６ｄおよびエピクロルヒドリン１
５１１Ｉｉ！を加えて攪拌しながら、４０℃で２時間反
応させ、エポキシ化ゲルをえた。えられたゲルに濃アン
モニア水２０ｄを加えて５０℃で２時間攪拌し、アミノ
基を導入した。Example 1 Cross-linked polyacrylate gel (totally porous hard gel) Toyobar +1) 165 (manufactured by Toyo 11 Lu > 10 m
6 d of saturated aqueous NaOH solution and 1 d of epichlorohydrin
511Ii! was added and reacted at 40° C. for 2 hours with stirring to obtain an epoxidized gel. 20 d of concentrated ammonia water was added to the resulting gel and stirred at 50°C for 2 hours to introduce amino groups.
えられたアミノ基を導入したゲル５ｄを、ポリアクリル
酸の１０％水１液（ｐＨ４，５に調整）に加えた。その
のち１−エチル−３−（ジメチルアミノプロピル）−カ
ルボジイミド３００Ｉｌ！ＩをｐＨを４．５に保ちなが
ら添加し、４℃で２４時間振盪した。The resulting amino group-introduced gel 5d was added to a solution of 10% polyacrylic acid in water (adjusted to pH 4.5). Then 300 Il of 1-ethyl-3-(dimethylaminopropyl)-carbodiimide! I was added while maintaining the pH at 4.5, and the mixture was shaken at 4°C for 24 hours.
反応終了後、２Ｈ食塩水溶液、０．５Ｈ食塩水溶液およ
び水を用いてこの順に洗浄し、ポリアクリル酸の固定さ
れたゲルをえた。After the reaction was completed, the gel was washed with a 2H saline solution, a 0.5H saline solution, and water in this order to obtain a gel on which polyacrylic acid was fixed.
実施例２
多孔質セルロースゲルであるＣにグルＡ−３（排除限界
分子口５０．０００．０００、粒径４５〜１０５μｍ、
チッソ■製） １０ａｄ！に水１０−を加えて全ｆｆｉ
２０ａｅとした。これに２ＨＮａＣζ５１ｍ１！、エ
ピクロルヒドリン１，８ｄを加えて攪拌しながら４０℃
で２時間反応させ、ゲルを水洗線通してエポキシ化セル
ロースゲルをえた。Example 2 Glue A-3 (exclusion limit molecular weight 50.000.000, particle size 45-105 μm,
Made by Chisso ■) 10ad! Add 10 - of water to the whole ffi
It was set to 20ae. 2HNaCζ51m1 for this! , add 1.8 d of epichlorohydrin and heat to 40°C while stirring.
After reacting for 2 hours, the gel was passed through a water washing line to obtain an epoxidized cellulose gel.
えられたゲル５ｄにデキストラン硫酸ナトリウム３ｇお
よび水５ｄを加え、ｐ１１９に調整して４５℃で１６時
間振盪した。そののちゲルを濾別して、２Ｈ食塩水溶液
、０．５Ｈ食塩水溶液および水を用いてこの順に洗浄し
、デキストラン硫酸ナトリウムが固定されたセルロース
ゲルをえた。3 g of dextran sodium sulfate and 5 d of water were added to the resulting gel (5 d), adjusted to p119, and shaken at 45° C. for 16 hours. Thereafter, the gel was filtered and washed with a 2H saline solution, a 0.5H saline solution, and water in this order to obtain a cellulose gel on which dextran sodium sulfate was immobilized.
実施例３
多孔質セルロースゲルであるセルロファインＧＣＬ−２
０００（チッソ■製、球状蛋白質の排除限界分子１３０
，０００．０００、粒径４５〜１０５μｍ、架橋ゲル）
１０ｄを取り、エタノール中で臨界点乾燥により乾燥さ
せた。乾燥ゲルを１０ｍのよく脱水したピリジン中に懸
濁させ氷冷した。これにクロルスルホン酸２ｍを攪拌下
に滴下し、滴下終了後１０分！７！ｌ攪拌をつづ（プた
。反応終了後ゲルを濾別し、ピリジンついで水で洗浄し
て、表面に硫酸残基が導入されたセルロースゲルをえた
。Example 3 Cellulofine GCL-2, a porous cellulose gel
000 (manufactured by Chisso ■, globular protein exclusion limit molecule 130
,000.000, particle size 45-105 μm, crosslinked gel)
10 d was taken and dried by critical point drying in ethanol. The dried gel was suspended in 10 m of well dehydrated pyridine and cooled on ice. Add 2 m of chlorosulfonic acid dropwise to this while stirring, and 10 minutes after the addition is complete! 7! After the reaction was completed, the gel was filtered and washed with pyridine and then water to obtain a cellulose gel with sulfuric acid residues introduced onto the surface.
つぎに実施例１〜３でえられた各吸着体の活性化補体成
分に対する吸着能力を以下の方法により評価した。Next, the ability of each adsorbent obtained in Examples 1 to 3 to adsorb activated complement components was evaluated by the following method.
健常人より血液を採取し、遠心分離により血清を分離し
た。つぎにえられた血清をポリスチレン製バイアルに入
れ、ミキサーにより攪拌し、さらに酢酸セルロース製メ
ンブランフィルタ−を数回通過させて補体を活性化した
。Blood was collected from a healthy person, and serum was separated by centrifugation. Next, the obtained serum was placed in a polystyrene vial, stirred with a mixer, and passed through a cellulose acetate membrane filter several times to activate complement.
実施例１〜３でえられた吸着体を生理食塩液で洗浄、平
衡化した後、各１ｊＩｉ！をそれぞれガラス製試験管に
取り、これに上記の活性化補体成分を含む血清５ｄをそ
れぞれ加えてミキサーで攪拌して３７′Ｃで１時間イン
キュベートした。インキュベートした後遠心分離により
吸着体を分離し、上澄み中のＣおよびＣ５８の濃度をラ
ブ３ａ
イオイムノアッセイ〈アップジョン（１１製）により測
定した。After washing and equilibrating the adsorbents obtained in Examples 1 to 3 with physiological saline, each 1jIi! were each placed in a glass test tube, 5 d of the serum containing activated complement components described above was added to each, stirred with a mixer, and incubated at 37'C for 1 hour. After incubation, the adsorbent was separated by centrifugation, and the concentrations of C and C58 in the supernatant were measured using Lab 3a Immunoassay (manufactured by Upjohn (manufactured by 11)).
これらの結果を第１表に示す。These results are shown in Table 1.
参考例１
上記でえられた活性化補体成分を含む血清５−をミキサ
ーで攪拌して３７℃で１時間インキュベートした轡、上
澄み中のＣおよびＣ５ａの瀘ａ
度をラディオイムノアッセイを用いて実施例１〜３と同
様にして測定した。Reference Example 1 The serum 5- containing activated complement components obtained above was stirred with a mixer and incubated at 37°C for 1 hour, and the filtration level of C and C5a in the supernatant was measured using radioimmunoassay. Measurements were made in the same manner as in Examples 1-3.
その結果を第１表に示す。The results are shown in Table 1.
［以下余白］
第 １ 表
実施例４
実施例２でえられた吸着体５１ｄｌをポリプロピレン製
ミニカラムに充填し、生理食塩液でよく洗浄した。つぎ
に膜型血漿分離器（プラズマフローＡＰ−０５１１、旭
メディカル■製）を用いて血漿交換回路を形成し、５％
アルブミン液を補充液として行なわれた血漿交換治療に
おいて、分離され廃棄される血漿を採取し、上記のカラ
ムに１１！１１／１ｎの速度で流し、カラム前後のＣ３
ａおよびＣ５ａの濃度を実施例１〜３と同様にして測定
した。[Margins below] Table 1 Example 4 51 dl of the adsorbent obtained in Example 2 was packed into a polypropylene minicolumn and thoroughly washed with physiological saline. Next, a plasma exchange circuit was formed using a membrane-type plasma separator (Plasma Flow AP-0511, manufactured by Asahi Medical ■), and 5%
In plasmapheresis treatment performed with albumin solution as a replenisher, the separated and discarded plasma was collected and passed through the above column at a speed of 11!11/1n, and the C3 before and after the column was collected.
The concentrations of a and C5a were measured in the same manner as in Examples 1-3.
その結果、用いた血漿中にはＣ３ａが２２３０ｎＱ／ｄ
ＳＣ５，が８２ｎＣ１／ ｌｉ！含まれていたが、カラ
ムより溶出した血漿中ではそれぞれ４１ｎｌ；ｌ／ ＃
Ｉｉ！、３０ｎｇ／ｄに減少していた。As a result, C3a was found to be 2230 nQ/d in the plasma used.
SC5, is 82nC1/li! However, in the plasma eluted from the column, each amount was 41nl; l/#
Ii! , decreased to 30 ng/d.
［発明の効果］
本発明の吸着体は活性化補体成分に対して優れた吸着力
を呈し、人工透析、人工心肺、血漿交換、血漿浄化など
の体外循環治療用吸着体として好適に使用しうる。[Effects of the Invention] The adsorbent of the present invention exhibits excellent adsorption power for activated complement components, and is suitably used as an adsorbent for extracorporeal circulation treatments such as artificial dialysis, artificial heart-lung therapy, plasma exchange, and plasma purification. sell.
手続補正書（自制 昭和６２年３月２日Procedural amendment (self-restraint) March 2, 1986
Claims (1)
補体成分の吸着体。 ２ 水不溶性多孔質物質である特許請求の範囲第１項記
載の吸着体。 ３ アニオン性官能基が硫酸エステル基である特許請求
の範囲第１項記載の吸着体。 ４ 水不溶性多孔質物質が水不溶性担体にアニオン性官
能基含有化合物を固定したものである特許請求の範囲第
２項記載の吸着体。 ５ アニオン性官能基含有化合物が硫酸エステル化合物
および／またはポリアニオン化合物である特許請求の範
囲第４項記載の吸着体。 ６ 活性化補体成分を含む溶液を、アニオン性官能基を
有する吸着体に接触させることを特徴とする活性化補体
成分の除去方法。 ７ アニオン性官能基を有する吸着体が体液の入口と出
口とを有する容器に充填されたものである特許請求の範
囲第６項記載の除去方法。[Scope of Claims] 1. An adsorbent for activated complement components, characterized by having an anionic functional group. 2. The adsorbent according to claim 1, which is a water-insoluble porous material. 3. The adsorbent according to claim 1, wherein the anionic functional group is a sulfate ester group. 4. The adsorbent according to claim 2, wherein the water-insoluble porous material is a water-insoluble carrier on which an anionic functional group-containing compound is fixed. 5. The adsorbent according to claim 4, wherein the anionic functional group-containing compound is a sulfate ester compound and/or a polyanionic compound. 6. A method for removing activated complement components, which comprises bringing a solution containing activated complement components into contact with an adsorbent having an anionic functional group. 7. The removal method according to claim 6, wherein the adsorbent having an anionic functional group is filled in a container having an inlet and an outlet for body fluid.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61005535A JPH0616842B2 (en) | 1986-01-14 | 1986-01-14 | Adsorbent for activated complement components |
| EP87100297A EP0230247A3 (en) | 1986-01-14 | 1987-01-13 | Adsorbent for removing complement component |
| JP3194168A JPH0738881B2 (en) | 1986-01-14 | 1991-08-02 | Container for removing activated complement components |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61005535A JPH0616842B2 (en) | 1986-01-14 | 1986-01-14 | Adsorbent for activated complement components |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3194168A Division JPH0738881B2 (en) | 1986-01-14 | 1991-08-02 | Container for removing activated complement components |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62191041A true JPS62191041A (en) | 1987-08-21 |
| JPH0616842B2 JPH0616842B2 (en) | 1994-03-09 |
Family
ID=11613881
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61005535A Expired - Lifetime JPH0616842B2 (en) | 1986-01-14 | 1986-01-14 | Adsorbent for activated complement components |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0616842B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02149341A (en) * | 1988-11-28 | 1990-06-07 | Kanegafuchi Chem Ind Co Ltd | Adsorbent for serum amyloid p-protein |
| WO2001068672A1 (en) * | 2000-03-13 | 2001-09-20 | Morinaga Milk Industry Co., Ltd. | Protein hydrolyzates, process for producing the same and drinks and foods containing the protein hydrolyzates |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58165860A (en) * | 1982-03-29 | 1983-09-30 | 旭化成株式会社 | Carrier of adsorbing material for purifying body liquid |
| JPS6090039A (en) * | 1983-10-21 | 1985-05-21 | Asahi Chem Ind Co Ltd | Blood purifying adsorbing body |
-
1986
- 1986-01-14 JP JP61005535A patent/JPH0616842B2/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58165860A (en) * | 1982-03-29 | 1983-09-30 | 旭化成株式会社 | Carrier of adsorbing material for purifying body liquid |
| JPS6090039A (en) * | 1983-10-21 | 1985-05-21 | Asahi Chem Ind Co Ltd | Blood purifying adsorbing body |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02149341A (en) * | 1988-11-28 | 1990-06-07 | Kanegafuchi Chem Ind Co Ltd | Adsorbent for serum amyloid p-protein |
| WO2001068672A1 (en) * | 2000-03-13 | 2001-09-20 | Morinaga Milk Industry Co., Ltd. | Protein hydrolyzates, process for producing the same and drinks and foods containing the protein hydrolyzates |
| US6908633B2 (en) | 2000-03-13 | 2005-06-21 | Morinaga Milk Industry Co., Ltd. | Protein hydrolyzates, process for producing the same and drinks and foods containing the protein hydrolyzates |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0616842B2 (en) | 1994-03-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0230247A2 (en) | Adsorbent for removing complement component | |
| JPS6090039A (en) | Blood purifying adsorbing body | |
| JPS62191041A (en) | Adsorbent of activated complementary component and removal of said component | |
| JPH01119264A (en) | Adsorbent and removing device therewith | |
| JPS59196738A (en) | Adsorbent and preparation thereof | |
| JPH02149341A (en) | Adsorbent for serum amyloid p-protein | |
| JPH01181875A (en) | Adsorptive body of immune complex and removing device for immune complex with it | |
| JPS59186558A (en) | Adsorbing material of self-antibody and/or immunological composite | |
| EP0320194B1 (en) | Absorbent for free hemoglobin | |
| JPS59169532A (en) | Adsorbing material of c-reactive protein | |
| JPS59186559A (en) | Self-antibody and/or immunological composite adsorbing material | |
| JP3157026B2 (en) | Adsorbent for blood purification | |
| JPS6087854A (en) | Adsorbent for purifying blood | |
| JPH0622632B2 (en) | Adsorbent and removal device | |
| JPH0592036A (en) | Method for removing activated complement component | |
| JPH024301B2 (en) | ||
| JPH0316639A (en) | Adsorbent and removing device using the same | |
| JPS5861752A (en) | Material and apparatus for adsorbing malodorous substance | |
| JP2726662B2 (en) | Adsorbent and removal device using the same | |
| JPS6259976B2 (en) | ||
| JPS62211073A (en) | Adsorbent for compliant component | |
| JPS62244442A (en) | Low specific gravity lipoprotein adsorbing material and its preparation | |
| JPS59139937A (en) | Adsorbent for lipoprotein with low specific gravity | |
| JP3084436B2 (en) | Anti-DNA antibody removal device | |
| JP3181343B2 (en) | Method for producing adsorbent material for body fluid purification |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |