JPS6282972A - bilirubin remover - Google Patents
bilirubin removerInfo
- Publication number
- JPS6282972A JPS6282972A JP60221164A JP22116485A JPS6282972A JP S6282972 A JPS6282972 A JP S6282972A JP 60221164 A JP60221164 A JP 60221164A JP 22116485 A JP22116485 A JP 22116485A JP S6282972 A JPS6282972 A JP S6282972A
- Authority
- JP
- Japan
- Prior art keywords
- adsorbent
- exchange resin
- bilirubin
- blood
- anion exchange
- 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 description 38
- 239000003957 anion exchange resin Substances 0.000 claims description 15
- 239000003146 anticoagulant agent Substances 0.000 claims description 13
- 239000008280 blood Substances 0.000 claims description 13
- 210000004369 blood Anatomy 0.000 claims description 13
- 229940127219 anticoagulant drug Drugs 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 230000002785 anti-thrombosis Effects 0.000 claims description 4
- 239000003463 adsorbent Substances 0.000 description 26
- 239000003456 ion exchange resin Substances 0.000 description 15
- 229920003303 ion-exchange polymer Polymers 0.000 description 15
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 238000001179 sorption measurement Methods 0.000 description 11
- 238000000576 coating method Methods 0.000 description 9
- 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 7
- 239000011248 coating agent Substances 0.000 description 7
- 229960002897 heparin Drugs 0.000 description 7
- 229920000669 heparin Polymers 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- SMEGJBVQLJJKKX-HOTMZDKISA-N [(2R,3S,4S,5R,6R)-5-acetyloxy-3,4,6-trihydroxyoxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@@H](O1)O)OC(=O)C)O)O SMEGJBVQLJJKKX-HOTMZDKISA-N 0.000 description 5
- 229940081735 acetylcellulose Drugs 0.000 description 5
- 229920002301 cellulose acetate Polymers 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 206010019663 Hepatic failure Diseases 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 208000007903 liver failure Diseases 0.000 description 3
- 231100000835 liver failure Toxicity 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 3
- 229920002307 Dextran Polymers 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000012503 blood component Substances 0.000 description 2
- 230000008081 blood perfusion Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000002616 plasmapheresis Methods 0.000 description 2
- 238000004381 surface treatment Methods 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 241000283986 Lepus Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- VFBJEDFCUUCMBQ-UHFFFAOYSA-O azanium;sodium;antimony(3+);oxygen(2-);tungsten Chemical compound [NH4+].[O-2].[Na+].[Sb+3].[W] VFBJEDFCUUCMBQ-UHFFFAOYSA-O 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 210000001953 common bile duct Anatomy 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 125000003010 ionic group Chemical group 0.000 description 1
- 229920000831 ionic polymer Polymers 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000003058 plasma substitute Substances 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical group CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
Landscapes
- External Artificial Organs (AREA)
Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、血液中のビリルビンの除去剤に関するもので
ある。DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to an agent for removing bilirubin from blood.
（従来の技術および解決すべき問題点）肝不全に対する
治療法として、近年、活性炭を用いた直接血液潅流やプ
ラズマフエレーシスなどが実施されるようになった。し
かしながら活性炭などにおいては蛋白結合性物質や高分
子量物質などの吸着除去は不完全であシ、プラズマフエ
レーシスでは多量の代用血漿が必要とされるなど解決す
べき問題も多い。(Prior Art and Problems to Be Solved) In recent years, direct blood perfusion using activated charcoal, plasmapheresis, and the like have been practiced as treatments for liver failure. However, activated carbon etc. cannot adsorb and remove protein-binding substances or high molecular weight substances incompletely, and plasmapheresis requires a large amount of plasma substitute, and there are many other problems that need to be solved.
（問題点を解決するための手段）
本発明者らは、肝不全時に増加する物質の一つであるビ
リルビンに溜目し、その除去剤につき鋭意研究した結果
、多孔性塩基性陰イオン交換樹脂が血液中のビリルビン
の除去剤として優れた効果を持つことを見出した。(Means for Solving the Problems) The present inventors have discovered that bilirubin, which is one of the substances that increases during liver failure, has accumulated, and as a result of intensive research into a removal agent, they have developed a porous basic anion exchange resin. was found to have excellent effects as a remover for bilirubin in the blood.
又多孔性塩基性陰イオン交換樹脂は長時間血液と接触さ
せるとヘパリンや血液有形成分を吸着して、樹脂粒内へ
の血液の浸透を阻害する現象が生じるが、樹脂の表面を
抗凝固剤で処理することにより、ヘパリン吸着が抑えら
れ、又抗血栓性材料でコーティングすることにより、血
液有形成分の付着を防止でさることを見出した０本発明
はこれらの知見をもとに完成されたものであり、その要
旨はその表面に抗凝固剤を反応させ、更にその表面を抗
血栓性高分子材料でコーティングした多孔性塩基性陰イ
オン交換樹脂からなる血液中のビリルビン除去剤に存す
る。Furthermore, when porous basic anion exchange resins are brought into contact with blood for a long period of time, they adsorb heparin and other blood components, inhibiting the penetration of blood into the resin granules. The present invention was completed based on these findings.The present invention was completed based on these findings.The present invention was completed based on these findings. The gist of this is that it is a blood bilirubin remover made of a porous basic anion exchange resin whose surface is reacted with an anticoagulant and further coated with an antithrombotic polymeric material. .
以下、本発明の詳細な説明する。The present invention will be explained in detail below.
本発明の多孔性塩基性陰イオン交換樹脂は、内部表面積
／ ｊ ｒｎ／１１以上（ＢＩＴ法で測定）の物理的細
孔を有する陰イオン交換樹脂であり、イオン交換基とし
てはトリメチルアンモニウム基、ジメチルエタノールア
ンモニウム基等のダ級アンモニウム基やジメチルアミノ
基、アミン基、コーアミノエチルアミノ基、６−アミノ
エチルアミノ基、コー（＝−アミノエチル）アミノエチ
ルアミノ基等の１１コ、３級アミン基を有する隘イオン
交換樹脂でめる。交換容には０、 ｊ ｍｅｑ／Ｊ’以
上、好ましくは八ｊ ｍｅｑ／ＩＪＩ以上のものが好適
である。The porous basic anion exchange resin of the present invention is an anion exchange resin having physical pores with an internal surface area / j rn /11 or more (measured by the BIT method), and the ion exchange group includes a trimethylammonium group, D-class ammonium groups such as dimethylethanolammonium group, dimethylamino group, amine group, co-aminoethylamino group, 6-aminoethylamino group, co-(=-aminoethyl)aminoethylamino group, etc., and tertiary amines. Filled with ion-exchange resin containing a group of ion-exchange resins. The exchange capacity is preferably 0.j meq/J' or more, preferably 8 j meq/IJI or more.
このような陰イオン交換樹脂は既に公知でるり、例えば
市販のイオン交換樹脂では、ダイヤイオンＨＰＡ−コＳ
、ダイヤイオンＨＰＡ−７１。Such anion exchange resins are already known; for example, commercially available ion exchange resins include Diaion HPA-CoS.
, Diaion HPA-71.
ダイヤイオンＯ−５，ダイヤイオンＡ−５，ダイヤイオ
ン０Ｒ−２０（三菱化成工業■登録商８Ａ）等が挙げら
れる。Diaion O-5, Diaion A-5, Diaion 0R-20 (Mitsubishi Chemical Industries, Ltd. Registered Trademark 8A), etc. are included.
本発明のビリルビン除去剤は上記の隘イオン交換樹脂の
表面に抗凝固剤を反応させ、更に抗血栓性高分子材料で
表面をコーティングしたものである。The bilirubin removing agent of the present invention is obtained by reacting an anticoagulant on the surface of the above-mentioned ion exchange resin, and further coating the surface with an antithrombotic polymeric material.
抗凝固剤としてはヘパリンが最もよく知られている物質
であるが、高価であるため、他の物質でも代用すること
ができる。テキストランスルホン酸ナトリウムは抗凝固
剤として好適に使用できる。Heparin is the most well-known anticoagulant, but it is expensive, so other substances can be used instead. Sodium textolansulfonate can be suitably used as an anticoagulant.
多孔性陰イオン交換樹脂と抗凝固剤との反応は、抗凝固
剤の水溶液とイオン交換樹脂を混合、接触させればよい
。The reaction between the porous anion exchange resin and the anticoagulant can be achieved by mixing and bringing the aqueous solution of the anticoagulant and the ion exchange resin into contact with each other.
抗凝固剤は陰イオン交換樹脂と、いわゆるポリイオンコ
ンプレックスを形成して、陰イオン交換樹脂の表面部を
被覆するものと推定される。It is presumed that the anticoagulant forms a so-called polyion complex with the anion exchange resin and coats the surface of the anion exchange resin.
抗凝固剤の使用量は、イオン交換樹脂の表面部のイオン
基と反応するに足る量でよい。The anticoagulant may be used in an amount sufficient to react with the ionic groups on the surface of the ion exchange resin.
本発明で使用される抗血栓性高分子材料としては、アセ
チルセルロース、ポリ酢酸ビニル、ポリヒドロキシエチ
ルメタクリレート、ポリメチルメタクリレート、ホルマ
ール化ポリビニルアルコールやこれらの共重合体、アル
ギン酸塩、ゼラチン、コラーゲン、等が挙げられる。Antithrombotic polymeric materials used in the present invention include acetylcellulose, polyvinyl acetate, polyhydroxyethyl methacrylate, polymethyl methacrylate, formalized polyvinyl alcohol, copolymers thereof, alginate, gelatin, collagen, etc. can be mentioned.
これらの高分子材料でイオン交換樹脂をコーティングす
る方法は特に限定されるものではないが、例えば次のよ
うな方法が挙げられる。The method of coating the ion exchange resin with these polymeric materials is not particularly limited, but examples include the following method.
一つは高分子材料の溶液と、多孔性塩基性陰イオン交換
樹脂とを混合接触させた後、イオン交換樹脂を戸別する
ことによって多孔性塩基性陰イオン交換樹脂の表面に高
分子材料の溶液を付着させ、ついで乾燥や抽出で溶媒を
除くことによっておこなわれる。One is to mix and contact a solution of a polymeric material with a porous basic anion exchange resin, and then transfer the ion exchange resin to the surface of the porous basic anion exchange resin. This is done by attaching a substance and then removing the solvent by drying or extraction.
この方法では高分子材料の溶液ｆＩｋ度を調節すること
によってイオン交換樹脂の表面をコーティングする高分
子材料の量を調節することができる。In this method, the amount of the polymeric material coating the surface of the ion exchange resin can be adjusted by adjusting the fIk degree of the solution of the polymeric material.
コーテイング量は高分子材料の種類によって適宜選択さ
れる。例えばアセチルセルロースの場合は、乾燥イオン
交換樹脂／ｌｉあたシ０．００／１１ないしはｏ、ｚ
１１、好ましくは０．０ ／ 、９ないしｏ、ｏ ３ｇ
である。コーテイング量が小であると、イオン交換樹脂
の表面に未コーティング部分が残って、血液有形成分付
着防止の効果が少なく、又コーテイング量が犬に過ぎる
とビリルビンの吸着を阻害することになるので好ましく
ない。The amount of coating is appropriately selected depending on the type of polymer material. For example, in the case of acetylcellulose, dry ion exchange resin/li at 0.00/11 or o,z
11, preferably 0.0/, 9 to o, o 3g
It is. If the amount of coating is too small, uncoated portions will remain on the surface of the ion exchange resin, which will have little effect on preventing the adhesion of blood particles, and if the amount of coating is too large, it will inhibit the adsorption of bilirubin. Undesirable.
他のコーティングの方法としては、高分子材料溶液をイ
オン交換樹脂の表面に噴霧しながら、乾燥する流動槽コ
ーティング法等によっておこなわれる。Other coating methods include a fluidized bath coating method in which a polymeric material solution is sprayed onto the surface of the ion exchange resin and then dried.
あるいは公知のマイクロカプセル法等も採用される。Alternatively, a known microcapsule method or the like may also be employed.
（発明の効果）
本発明のビリルビン除去剤は、ヘパリンや血液有形成分
の吸着が少いので直接血液、ｆＩ流の吸着剤として使用
され、肝不全の治療に有効なものである。(Effects of the Invention) The bilirubin removing agent of the present invention has little adsorption of heparin and blood components, so it can be directly used as an adsorbent for blood and fl flow, and is effective in treating liver failure.
（実施例）
以下、本発明を実施例によシ更に具体的に説明するが、
本発明は、その要旨を超えない限り以下の実施例に限定
されない。(Examples) Hereinafter, the present invention will be explained in more detail with reference to Examples.
The present invention is not limited to the following examples unless it exceeds the gist thereof.
実施例／（吸着剤の製造）
乾燥した多孔性塩基性陰イオン交換樹脂ダイヤイオンＨ
ＰＡ−２，１ｔ、コ５ｏｔｉと所定濃度のデキストラン
スルホン酸ナトリウム（分子Ｈｒｏｏ、ｏｏｏ）水溶液
１０１００Ｏとを室温で６０分混合、接触させて反応さ
せた後、イオン交換樹脂を戸別した。Examples/(Manufacture of adsorbent) Dried porous basic anion exchange resin Diaion H
PA-2,1t, Co5oti and 10,100 O of an aqueous solution of sodium dextran sulfonate (molecules Hroo, ooo) at a predetermined concentration were mixed at room temperature for 60 minutes and brought into contact to react, and then the ion exchange resin was sent from door to door.
次いでこれを１０００−のアセトンで洗浄して脱水をお
こなった。次いでこれと／重量−のアセチルセルロース
（アセチル基金ｆ［Ｊ ９．ｇ％）のアセトン溶液１０
００−とを室温で３０分混合接醜させた後、イオン交換
樹脂を戸別し、更に、２．Ｓ−℃で減圧乾燥しアセトン
を除去した。Next, this was washed with 1000-mL acetone to dehydrate it. Then, an acetone solution of this and acetyl cellulose (acetyl fund f [J 9.g%) /wt.
After 30 minutes of mixing with 2. The acetone was removed by drying under reduced pressure at S-°C.
吸着剤 使用したテキストランスルホン酸ナトリウ
ム水溶液＃１度
吸着剤−／ １０ 重量％吸着剤−
２５
吸着剤−３／、２！； ＃
比較例／（テキストランスルホン酸ナトリウム処理のみ
をおこなった吸着剤の製造）
乾燥した多孔性塩基性陰イオン交換樹脂、ダイヤイオン
ＨＰＡ−２左、２！０１１とへコｊ重量％デキストラン
スルホン酸ナトリウム（分子量ｓｏｏ、ｏｏｏ）水溶液
１０００−とを室温で６０分混合接触させた後イオン交
換樹脂を炉別した。次いでこれを１０００ｔｒｔｌのア
セトンで洗浄して、脱水をおこない、更に２！℃で減圧
乾燥しアセトンを除去した。Adsorbent: Texturan sodium sulfonate aqueous solution used #1 degree adsorbent - / 10% by weight adsorbent -
25 Adsorbent-3/, 2! # Comparative Example/(Manufacture of adsorbent treated only with sodium textran sulfonate) Dry porous basic anion exchange resin, Diaion HPA-2 left, 2!011 and Hecoj wt% dextrans sulfone The ion exchange resin was mixed and contacted with an aqueous solution of sodium chloride (molecular weight: soo, ooo) for 60 minutes at room temperature, and then the ion exchange resin was separated from the furnace. Next, this was washed with 1000 trtl of acetone, dehydrated, and further washed with 2! The acetone was removed by drying under reduced pressure at °C.
比Ｍ例！（アセチルセルロースコーティングのみをおこ
なった吸着剤の製造）
乾燥した多孔性塩基性陰イオン交換樹脂、ダイヤイオン
ＨＰＡ−２５、，２５０１１と７重量％のアセチルセル
ロース（アセチル基含有率、７？、５％）のアセトン溶
液１０００−とを室温で３０分間混合接触させた後、イ
オン′９．換樹脂を戸別し、次いで−Ｓ℃で減圧乾燥し
、アセトンを除去した０実施例２（ヘパリン吸着試験）
生理食塩水にヘパリンを加えて／ ０００ ｕ／ｄｌと
した試験溶液１００−に下記の吸着剤を各々／１を加え
て、３７℃で７時間振盪、混合した。Ratio M example! (Production of adsorbent with only acetylcellulose coating) Dried porous basic anion exchange resin, Diaion HPA-25, 25011 and 7% by weight acetylcellulose (acetyl group content, 7?, 5%) ) with an acetone solution 1000- of ion '9.) at room temperature for 30 minutes. Example 2 (Heparin adsorption test) The following test solution was added to the test solution 100-000 u/dl by adding heparin to physiological saline. A 1/1 ratio of each adsorbent was added, and the mixture was shaken and mixed at 37°C for 7 hours.
振盪後−００μｔの液を採取し、これとピーグル犬より
採血した血液−一とをヘモクロンテストチューブに加え
て混和し、へそクロン時間（血液が凝固する迄の時間）
を測定した０吸着剤として、実施例／の吸着剤−３，比
較例／で製造した吸着剤、比較例コで製造した吸着剤、
全く何も処理を施さないダイヤイオンＨＰＡ−，２ｊを
使用した。After shaking, -00 μt of liquid was collected, and this and blood sampled from a pegle dog were added to a hemoclone test tube and mixed, and the hemochron time (time until blood coagulated) was measured.
The adsorbents for which 0 was measured were Adsorbent-3 of Example/, Adsorbent manufactured in Comparative Example/, Adsorbent manufactured in Comparative Example-3,
Diamond Ion HPA-, 2j which was not subjected to any treatment was used.
結果は図−／のとおりで、本発明の吸着剤はヘパリンの
吸着が少いためへモクロン時間が非常に長かった。The results are shown in Figure -/, and the adsorbent of the present invention had a very long hemochron time because it adsorbed little heparin.
実施例３（ビリルビン吸着試験）
ユＯＷｑのビリルビンを１００ｍ１の脱塩水に浴解し、
これに実施例λと同じ吸着剤各１ｊ９を加えて、３７℃
で、３時間混合接触させた０この間の液中のビリルビン
濃度の変化を測定した。Example 3 (Bilirubin adsorption test) Bilirubin from YuOWq was dissolved in 100 ml of demineralized water,
Add 1j9 each of the same adsorbents as in Example λ to this, and heat at 37°C.
Then, the changes in the bilirubin concentration in the liquid were measured during the 3-hour mixing and contact period.
結果は図−一のとおりで、本発明の吸着剤は、表面処理
を施してもビリルビンの吸着能が、良好であることが示
されている。The results are shown in Figure 1, indicating that the adsorbent of the present invention has good bilirubin adsorption ability even after surface treatment.
実施例ダ（ビリルビン吸着試験）
２０■のビリルビンを１００−の脱塩水に溶解し、これ
に下記の吸着剤を各々、Ｏ０／９．０、．３１１．０．
５１を加え、３７℃で２１Ｉ時間振盪混和し、２弘時間
後の液中のビリルビン濃度を測定し各吸着剤の等温吸着
曲線を求めた。Example D (Bilirubin adsorption test) 20 μm of bilirubin was dissolved in 100 μm of demineralized water, and the following adsorbents were added to it, respectively, O0/9.0, . 311.0.
51 was added and mixed by shaking at 37° C. for 21 hours, and the bilirubin concentration in the liquid was measured after 2 hours to determine the isothermal adsorption curve of each adsorbent.
吸着剤として、実施例／の吸着剤−７〜吸着剤−３及び
何も処理を施こさないＨＰＡ−コＳを用いた。As adsorbents, Adsorbent-7 to Adsorbent-3 in Examples/1 and HPA-CoS which was not subjected to any treatment were used.
結果は図−３に示すとおりであった。The results were as shown in Figure 3.
本発明の吸着剤は表面処理によって、ビリルビンの吸着
性能が多少低下はしているが、充分に大であることが示
される。Although the adsorbent of the present invention has a somewhat reduced bilirubin adsorption ability due to surface treatment, it is shown to be sufficiently high.
実施例１Ｉ（動物実験）
吸着剤１Ｉｏｙを充填したカラム（直径ｊ ａｎ ）を
用い、総胆管結紮離断、胆のう一後大静脈吻合した実験
的黄痘犬に対し、血液蓋１００ｍｔ／ｍで３時間の血＆
溢流をおこない、海流中の血清ビリルビン値、血小板、
カラム圧力損失の変動を測定した。Example 1I (animal experiment) Using a column (diameter J an ) packed with 1 Ioy of adsorbent, an experimental dog with jaundice in which the common bile duct was ligated and transected and the gallbladder was anastomosed with the vena cava was treated with a blood cap of 100 mt/m for 3 blood of time &
The serum bilirubin level, platelets,
The variation in column pressure drop was measured.
吸着剤は実施例／の吸着剤−３と比較例−の吸着剤と何
も処理を施こさないＨＰＡ−２３を使用した。The adsorbents used were Adsorbent-3 in Example, Adsorbent in Comparative Example, and HPA-23 which was not subjected to any treatment.
結果を図−ダ、図−３１図−６に示す。The results are shown in Figure-Da, Figure-31 and Figure-6.
本発明の吸着剤は血小板の吸着も少なく、カ２ムの圧力
損失の変化もなく順調に血液！ＩＩ流がおこなえて、か
つビリルビンの吸着も良好であった０
何も処理を施こさない吸着剤は、すぐにカラムの圧力損
失が高くなり、血液潅流が実施できなかった。The adsorbent of the present invention adsorbs less platelets and smoothly absorbs blood without any change in pressure loss in the chamber. Flow II could be carried out, and bilirubin was adsorbed well. With the adsorbent that was not subjected to any treatment, the pressure drop in the column immediately increased, and blood perfusion could not be carried out.
又、比較例コの吸着剤の場合も血小板の吸着が大であっ
たシ、カラムの圧力損失が経時と共に増大するという問
題を示した。In addition, the adsorbent of Comparative Example 1 also exhibited a problem in that the adsorption of platelets was large and the pressure loss in the column increased with time.
図−／は実施例−におけるヘパリン吸着試験の結果を示
す図であり、図−コおよび図−３は、各々、実施例３お
よび弘におけるとリルビン吸着試験の結果を示す図であ
る。
図−弘一図−６は実施例ダの結果を示す図であり、図中
・は実施例／の吸着剤−３を、Ｇは比較例−の吸着剤を
示す。
出 願 人 三羨化成工莱株式会社
代 理 人 弁理士長谷用 −
ほか７名
図−ｆ
時間
し′１ルごン平イ到し褒Ｕ （／％会γ２）巳−４
（ｍｍＨｇ）＞訃６
Ｐｙ聞Figure-/ is a diagram showing the results of a heparin adsorption test in Example-, and Figure-C and Figure-3 are diagrams showing the results of a rilubin adsorption test in Example 3 and Hiro, respectively. Figure-Koichi Figure-6 is a diagram showing the results of Example D. In the figure, * indicates the adsorbent of Example/3, and G indicates the adsorbent of Comparative Example-. Applicant: Sankyen Kasei Korai Co., Ltd. Agent: Patent Attorney Hase - 7 others Fig. F Time: 1,000 yen (/% γ2) -4 (mmHg)> Death 6 Py hearing
Claims (1)
抗血栓性高分子材料でコーティングした多孔性塩基性陰
イオン交換樹脂からなる血液中のビリルビン除去剤(1) An agent for removing bilirubin from blood, which is made of a porous basic anion exchange resin whose surface is reacted with an anticoagulant and further coated with an antithrombotic polymeric material.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60221164A JPH0651064B2 (en) | 1985-10-04 | 1985-10-04 | Bilirubin remover |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60221164A JPH0651064B2 (en) | 1985-10-04 | 1985-10-04 | Bilirubin remover |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6282972A true JPS6282972A (en) | 1987-04-16 |
| JPH0651064B2 JPH0651064B2 (en) | 1994-07-06 |
Family
ID=16762472
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60221164A Expired - Lifetime JPH0651064B2 (en) | 1985-10-04 | 1985-10-04 | Bilirubin remover |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0651064B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63275351A (en) * | 1987-05-07 | 1988-11-14 | Kuraray Co Ltd | Blood purifying apparatus |
| CN104147653A (en) * | 2014-08-27 | 2014-11-19 | 珠海健帆生物科技股份有限公司 | Blood perfusion device having anti-coagulation function and controlled-release function and manufacturing method thereof |
-
1985
- 1985-10-04 JP JP60221164A patent/JPH0651064B2/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63275351A (en) * | 1987-05-07 | 1988-11-14 | Kuraray Co Ltd | Blood purifying apparatus |
| CN104147653A (en) * | 2014-08-27 | 2014-11-19 | 珠海健帆生物科技股份有限公司 | Blood perfusion device having anti-coagulation function and controlled-release function and manufacturing method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0651064B2 (en) | 1994-07-06 |
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