JPH0320257B2 - - Google Patents
Info
- Publication number
- JPH0320257B2 JPH0320257B2 JP59189196A JP18919684A JPH0320257B2 JP H0320257 B2 JPH0320257 B2 JP H0320257B2 JP 59189196 A JP59189196 A JP 59189196A JP 18919684 A JP18919684 A JP 18919684A JP H0320257 B2 JPH0320257 B2 JP H0320257B2
- Authority
- JP
- Japan
- Prior art keywords
- methionine
- amino acid
- bag
- cells
- blood
- 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.)
- Expired - Lifetime
Links
- 239000008280 blood Substances 0.000 claims description 19
- 210000004369 blood Anatomy 0.000 claims description 19
- 150000001413 amino acids Chemical class 0.000 claims description 15
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 12
- 229920000642 polymer Polymers 0.000 claims description 12
- 229930182817 methionine Natural products 0.000 claims description 11
- 229940024606 amino acid Drugs 0.000 description 14
- 235000001014 amino acid Nutrition 0.000 description 14
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 229960004452 methionine Drugs 0.000 description 11
- 239000000463 material Substances 0.000 description 8
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 6
- 239000007800 oxidant agent Substances 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- 239000011521 glass Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000000465 moulding Methods 0.000 description 3
- 108010087948 polymethionine Proteins 0.000 description 3
- 229920000915 polyvinyl chloride Polymers 0.000 description 3
- 239000004800 polyvinyl chloride Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- 229960003767 alanine Drugs 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 229930195722 L-methionine Natural products 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- -1 N-carboxyamino acid anhydride Chemical class 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001509 aspartic acid derivatives Chemical class 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 229960005215 dichloroacetic acid Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002668 lysine derivatives Chemical class 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 238000007781 pre-processing Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
Landscapes
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Description
(a) 発明の技術分野
本発明は、酸化処理されたメチオニンを含むア
ミノ酸重合体を内表面に有することにより、細胞
が付着しにくいことを特徴とする血液バツグに関
するものである。
血液バツグとは輸血用の血液を保存する袋状容
器である。
(b) 従来技術の説明
従来、血液バツグは、シリコーンゴム、ポリウ
レタン、ポリ塩化ビニル等の合成高分子材料を用
いて作製されている。これらの材料を用いた血液
バツグでは、その材料表面に細胞が付着し、血液
の組成が変化する。したがつて、血液バツグにお
いては細胞の付着しない材料が求められている。
(c) 発明の目的
本発明は上記の問題を、酸化処理されたメチオ
ニンを含むアミノ酸重合体を用いることにより、
細胞付着の少ない血液バツグを提供することを目
的とする。
(d) 発明の構成
本発明者は細胞の付着しにくい性質を有する材
料について種々研究を重ねたところ、メチオニン
を含むアミノ酸重合体を酸化処理したものは、細
胞を著しく付着させない性質を有しており、血液
バツグとして好適であることを見い出し、本発明
を完成するに到つた。
即ち、本発明の血液バツグは、メチオニンを含
むアミノ酸重合体を目的とする形状に成型したの
ち、その成型物を過酸化水素等の酸化剤で酸化処
理して得るか、あるいはあらかじめ他の高分子材
料で目的とする形状に成型した後、その内表面に
メチオニンを含むアミノ酸重合体を塗布し、その
後、酸化剤で酸化処理して得る。
本発明のアミノ酸重合体構成素材としてのメチ
オニン及びその共重合体として用いるアミノ酸は
Ｄ体、Ｌ体、ラセミ体でもよく、他のアミノ酸と
してアラニン、グリシン、ロイシン、バリン、グ
タミン酸誘導体、アスパラギン酸誘導体、リジン
誘導体、オルチニン誘導体などが用いられる。
アミノ酸重合体の分子量は、バツグの表面に塗
布する場合、少なくとも5000以上なければなら
ず、また、アミノ酸重合体それ自体でバツグを成
型する場合、少なくとも7000以上なければならな
い。重合体中のメチオニン含量はアミノ酸の種類
による変化するが、好ましくは、30モル％以上で
ある。
酸化処理剤として、過酸化水素、過酢酸、ヨウ
素とヨウ素酸塩などの慣用の酸化剤が用いられ
る。酸化処理時間は酸化剤の種類、濃度、温度及
びアミノ酸の種類、共重合組成に応じて適宜選択
するがいずれにしても、酸化処理により、血液バ
ツグの内表面部分のメチオニン成分はそのスルホ
キシドの段階までに酸化されるのが望ましい。
(e) 発明の実施例
次に本発明を実施例によりさらに詳細に説明す
る。
実施例 １
ポリ−Ｌ−メチオニンをテトラクロルエタンに
溶解して、ガラス板上に流し、風乾して皮膜（膜
厚0.054mm）を得た。この皮膜を15％の過酸化水
素水溶液に室温で35分間浸漬して酸化処理を行つ
た後、熱水中に８時間以上浸漬した。
酸化処理皮膜上に、人由来の上皮性細胞を含む
培養液（約10万個／ml）を接触させたまま、炭酸
ガス濃度５％、湿度100％、37℃の部屋に静置し、
17時間後、皮膜をリン酸緩衝液でかるく洗浄し
て、皮膜上に付着している細胞の量を核染色法に
より定量した。比較のため血液バツグに使用され
ているポリ塩化ビニル、標準試料として市販の細
胞培養シートを用いて、同様の細胞付着試験を行
つた。皮膜に付着した細胞の量を、標準試料に付
着した細胞の量で割ることにより、細胞付着率を
求めた。その結果を第１表に示す。
(a) Technical Field of the Invention The present invention relates to a blood bag that is characterized by having an oxidized methionine-containing amino acid polymer on its inner surface, making it difficult for cells to adhere to it. A blood bag is a bag-like container that stores blood for transfusion. (b) Description of the Prior Art Conventionally, blood bags have been made using synthetic polymeric materials such as silicone rubber, polyurethane, and polyvinyl chloride. In blood bags made of these materials, cells adhere to the material surface and the composition of the blood changes. Therefore, for blood bags, there is a need for materials to which cells do not adhere. (c) Purpose of the Invention The present invention solves the above problem by using an amino acid polymer containing oxidized methionine.
The purpose is to provide a blood bag with less cell adhesion. (d) Structure of the Invention The present inventor has conducted various studies on materials that have properties that make it difficult for cells to attach to them, and has found that oxidation-treated amino acid polymers containing methionine have properties that do not allow cells to attach significantly. The present inventors have discovered that it is suitable as a blood bag, and have completed the present invention. That is, the blood bag of the present invention can be obtained by molding a methionine-containing amino acid polymer into a desired shape and then oxidizing the molded product with an oxidizing agent such as hydrogen peroxide, or by pre-processing the molded product with an oxidizing agent such as hydrogen peroxide. After molding the material into the desired shape, an amino acid polymer containing methionine is applied to the inner surface of the material, and then oxidation treatment is performed with an oxidizing agent. Methionine as a constituent material of the amino acid polymer of the present invention and the amino acid used as its copolymer may be D-form, L-form, or racemic form, and other amino acids include alanine, glycine, leucine, valine, gutamic acid derivatives, and aspartic acid derivatives. , lysine derivatives, ortinine derivatives, etc. are used. The molecular weight of the amino acid polymer must be at least 5,000 when applied to the surface of the bag, and must be at least 7,000 when the bag is molded from the amino acid polymer itself. The methionine content in the polymer varies depending on the type of amino acid, but is preferably 30 mol% or more. As the oxidizing agent, conventional oxidizing agents such as hydrogen peroxide, peracetic acid, iodine and iodate are used. The oxidation treatment time is appropriately selected depending on the type, concentration, and temperature of the oxidizing agent, the type of amino acid, and the copolymerization composition. It is desirable that it be oxidized by (e) Examples of the invention Next, the present invention will be explained in more detail using examples. Example 1 Poly-L-methionine was dissolved in tetrachloroethane, poured onto a glass plate, and air-dried to obtain a film (thickness: 0.054 mm). This film was oxidized by immersing it in a 15% aqueous hydrogen peroxide solution at room temperature for 35 minutes, and then immersed in hot water for 8 hours or more. A culture solution containing human-derived epithelial cells (approximately 100,000 cells/ml) was left in contact with the oxidized film and left in a room at 37°C with a carbon dioxide concentration of 5% and humidity of 100%.
After 17 hours, the film was washed briefly with phosphate buffer, and the amount of cells adhering to the film was quantified by nuclear staining. For comparison, a similar cell adhesion test was conducted using polyvinyl chloride used in blood bags and a commercially available cell culture sheet as a standard sample. The cell attachment rate was determined by dividing the amount of cells attached to the film by the amount of cells attached to the standard sample. The results are shown in Table 1.
【表】
実施例 ２
Ｌ−メチオニンとＬ−アラニンとからなる共重
合体をＮ−カルボキシアミノ酸無水物法により合
成し、重合溶媒として、ベンゼン、メチレンクロ
ライド、ジオキサン、Ｎ，Ｎ−ジメチルホルムア
ミドの混合物を用いた。共重合体中のメチオニン
含量が33％、49％、63％の３種類を合成し、クロ
ロホルムとジクロル酢酸との混合溶媒を用いて溶
解して、ガラス板上に流し、風乾して皮膜を得
た。この皮膜を15％の過酸化水素水溶液に室温で
20分間浸漬して酸化処理を行つた。
実施例 ３
ガラス容器の内表面にメチオニン含有アミノ酸
重合体を塗布し乾燥させ、15％の過酸化水素水溶
液に室温で35分間浸漬して酸化処理を行い、乾燥
後ガラス容器からはずし、袋状容器を得た。
実施例 ４
血液バツグ用に裁断したポリ塩化ビニル製のシ
ートの片面に、ポリ−Ｌ−メチオニンのテトラク
ロルエタン溶液（濃度0.21％）を塗布し、乾燥に
よりテトラクロルエタンを蒸発させた。このシー
トの塗布面がバツグの内側になるように血液バツ
グを組み立て、ヒートシールにより可撓性袋状容
器を作成した。この後、この容器に15％の過酸化
水素水溶液を入れ、室温で30分間酸化処理を行つ
た。さらに、熱水で十分に洗浄して血液バツグを
得た。
実施例 ５
実施例１と同様にして、ポリ−Ｌ−メチオニン
の皮膜を血液バツグ用の形に裁断し、接着加工し
てバツグを作成した。この後、この容器に15％の
過酸化水素水溶液を入れ、室温で30分間酸化処理
を行つた。さらに、熱水で十分に洗浄して血液バ
ツグを得た。
(f) 発明の効果
本発明は以上説明したように、細胞付着の少な
いことを必要とする血液バツグにおいて、酸化処
理されたメチオニンを含むアミノ酸重合体を内表
面に成型することにより細胞の付着を抑え、か
つ、この血液バツグを任意の形状で得ることが可
能である。[Table] Example 2 A copolymer consisting of L-methionine and L-alanine was synthesized by the N-carboxyamino acid anhydride method, and a mixture of benzene, methylene chloride, dioxane, and N,N-dimethylformamide was used as the polymerization solvent. was used. Three types of copolymers with methionine contents of 33%, 49%, and 63% were synthesized, dissolved using a mixed solvent of chloroform and dichloroacetic acid, poured onto a glass plate, and air-dried to obtain a film. Ta. This film was soaked in a 15% hydrogen peroxide solution at room temperature.
Oxidation treatment was performed by soaking for 20 minutes. Example 3 A methionine-containing amino acid polymer was applied to the inner surface of a glass container, dried, and oxidized by immersing it in a 15% hydrogen peroxide aqueous solution at room temperature for 35 minutes. After drying, it was removed from the glass container and placed in a bag-like container. I got it. Example 4 A solution of poly-L-methionine in tetrachloroethane (concentration 0.21%) was applied to one side of a polyvinyl chloride sheet cut for blood bags, and the tetrachloroethane was evaporated by drying. A blood bag was assembled so that the coated surface of this sheet was on the inside of the bag, and a flexible bag-like container was created by heat sealing. Thereafter, a 15% aqueous hydrogen peroxide solution was placed in this container, and oxidation treatment was performed at room temperature for 30 minutes. Furthermore, blood bags were obtained by thoroughly washing with hot water. Example 5 In the same manner as in Example 1, a poly-L-methionine film was cut into a shape for a blood bag and adhesively processed to make a bag. Thereafter, a 15% aqueous hydrogen peroxide solution was placed in this container, and oxidation treatment was performed at room temperature for 30 minutes. Furthermore, blood bags were obtained by thoroughly washing with hot water. (f) Effects of the Invention As explained above, the present invention reduces the adhesion of cells by molding an amino acid polymer containing oxidized methionine on the inner surface of a blood bag that requires less adhesion of cells. It is possible to obtain this blood bag in any desired shape.
Claims (1)
合体を内表面に有する血液バツグ1 Blood bag with an amino acid polymer containing oxidized methionine on its inner surface
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59189196A JPS6168046A (en) | 1984-09-10 | 1984-09-10 | Blood bag |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59189196A JPS6168046A (en) | 1984-09-10 | 1984-09-10 | Blood bag |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6168046A JPS6168046A (en) | 1986-04-08 |
| JPH0320257B2 true JPH0320257B2 (en) | 1991-03-19 |
Family
ID=16237125
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59189196A Granted JPS6168046A (en) | 1984-09-10 | 1984-09-10 | Blood bag |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6168046A (en) |
-
1984
- 1984-09-10 JP JP59189196A patent/JPS6168046A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6168046A (en) | 1986-04-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Balakrishnan et al. | Chemical modification of poly (vinyl chloride) resin using poly (ethylene glycol) to improve blood compatibility | |
| Rehakova et al. | Properties of collagen and hyaluronic acid composite materials and their modification by chemical crosslinking | |
| Yuan et al. | Grafting sulfobetaine monomer onto the segmented poly (ether-urethane) surface to improve hemocompatibility | |
| CN109731137B (en) | Preparation method of albumin coating with biological antifouling function and material with biological antifouling function | |
| US4530974A (en) | Nonthrombogenic articles having enhanced albumin affinity | |
| EP0333730B1 (en) | Process for producing non-thrombogenic substrates | |
| JPH07184989A (en) | Hemocompatible medical polymeric materials and medical materials | |
| EP0061312B1 (en) | Alkyl-substituted polymers having enhanced albumin affinity | |
| JPH0669485B2 (en) | Molded product containing silk fibroin | |
| Liu et al. | Synthesis and antithrombogenicity of heparinized polyurethanes with intervening spacer chains of various kinds | |
| CN120943940B (en) | Anti-coagulation coating based on tick-derived anti-coagulation protein QINGHAIENIN and preparation method thereof | |
| JPS6168046A (en) | Blood bag | |
| JPS6352908B2 (en) | ||
| JPS6352906B2 (en) | ||
| US4387183A (en) | Thromboresistant molded article and method for its production | |
| JPS644470B2 (en) | ||
| JPH0311783B2 (en) | ||
| JPS6168553A (en) | Protective film for sensor | |
| JPH11226113A (en) | Blood compatible polyurethane-hydrophilic high polymer blend | |
| US3316120A (en) | Process for preparing topcoated plasticized non-fibrous regenerated cellulose film and the resultant product | |
| JPH02233128A (en) | Oxygen permeable membrane | |
| JPS6352905B2 (en) | ||
| JPH028739B2 (en) | ||
| DE58901526D1 (en) | METHOD FOR IONIC NETWORKING OF AN ETHYLENE COPOLYMER. | |
| JPS644469B2 (en) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EXPY | Cancellation because of completion of term |