JPS644470B2 - - Google Patents
Info
- Publication number
- JPS644470B2 JPS644470B2 JP59133954A JP13395484A JPS644470B2 JP S644470 B2 JPS644470 B2 JP S644470B2 JP 59133954 A JP59133954 A JP 59133954A JP 13395484 A JP13395484 A JP 13395484A JP S644470 B2 JPS644470 B2 JP S644470B2
- Authority
- JP
- Japan
- Prior art keywords
- leucine
- amino acid
- film
- blood
- acid polymer
- 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
Links
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 26
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 15
- 150000001413 amino acids Chemical class 0.000 claims description 15
- 229920000642 polymer Polymers 0.000 claims description 13
- 239000008280 blood Substances 0.000 claims description 12
- 210000004369 blood Anatomy 0.000 claims description 12
- 229960003136 leucine Drugs 0.000 description 20
- 229940024606 amino acid Drugs 0.000 description 14
- 235000001014 amino acid Nutrition 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 229920001577 copolymer Polymers 0.000 description 7
- 239000004395 L-leucine Substances 0.000 description 6
- 235000019454 L-leucine Nutrition 0.000 description 6
- HFZKKJHBHCZXTQ-JTQLQIEISA-N (4s)-4-azaniumyl-5-oxo-5-phenylmethoxypentanoate Chemical compound OC(=O)CC[C@H](N)C(=O)OCC1=CC=CC=C1 HFZKKJHBHCZXTQ-JTQLQIEISA-N 0.000 description 5
- 230000021164 cell adhesion Effects 0.000 description 5
- 238000000465 moulding Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229920001400 block copolymer Polymers 0.000 description 3
- DHQUQYYPAWHGAR-UHFFFAOYSA-N dibenzyl 2-aminopentanedioate Chemical compound C=1C=CC=CC=1COC(=O)C(N)CCC(=O)OCC1=CC=CC=C1 DHQUQYYPAWHGAR-UHFFFAOYSA-N 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 229920002379 silicone rubber Polymers 0.000 description 2
- 239000004945 silicone rubber Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical class NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 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
- -1 N-carboxyamino acid anhydride Chemical class 0.000 description 1
- 238000000944 Soxhlet extraction Methods 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
- 150000001509 aspartic acid derivatives Chemical class 0.000 description 1
- 210000004204 blood vessel Anatomy 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
- 238000004581 coalescence Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 150000002668 lysine derivatives Chemical class 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 108010050934 polyleucine Proteins 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Description
(a) 発明の技術分野
本発明は、ロイシ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導管に関するものである。
血液導管とは人工血管、カテーテル、シヤント
（血液を体外に導き出すために用いるもの）、透析
型人工腎臓、膜型人工肺、人工心臓などに用いら
れている管状の血液の流路を包含するものであ
る。
(b) 従来技術の説明
従来、血液導管は、シリコーンゴム、ポリウレ
タン、テトラフルオロエチレン等の合成高分子材
料を用いて作製されているが、これらの材料を用
いた血液導管では、その材料表面に細胞が付着
し、すなわち血栓が生じ、血流を阻害する。した
がつて、血液導管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、ロイシンを含むアミノ
酸重合体を用いることにより、細胞付着性の少な
い血液導管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、ロイシンを
含むアミノ酸重合体は、細胞を著しく付着させな
い性質を有しており、血液導管として好適である
ことを見い出し、本発明を完成するに到つた。
即ち、本発明の血液導管は、ロイシンを含むア
ミノ酸重合体を目的とする管状に成型して得る
か、あるいはあらかじめ他の高分子材料で管状に
成型した後、その内表面にロイシンを含むアミノ
酸重合体を塗布して得る。
本発明のアミノ酸重合体構成素材としてのロイ
シン及びその共重合成分としてのアミノ酸は、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、メチオニン、バリン、
グルタミン酸誘導体、アスパラギン酸誘導体、リ
ジン誘導体、オルニチン誘導体などが用いられ
る。アミノ酸重合体の分子量はその皮膜が形成さ
れる程度であればよく、また重合体中のロイシン
含量はアミノ酸の種類によつて変わるが、30モル
％以上が好ましい。
(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
Ｌ−ロイシンとＬ−グルタミン酸ベンジルとの
共重合体（ロイシンとグルタミン酸ベンジルとの
モル比＝７：３）のベンゼンとジオキサン（７：
３）との混合溶液をガラス板上に流延し、風乾し
て皮膜（膜厚約0.05mm）を得た。この皮膜をエタ
ノールでソツクスレー抽出を行つた後、乾燥し
た。
この皮膜上で、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℃の部屋に静置した。
17時間後、皮膜をリン酸緩衝液で軽く洗浄し、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、グルタミン酸ベンジル単独
重合体皮膜及び血液導管に使用されているシリコ
ーンゴム、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 conduit characterized by having an amino acid polymer containing leucine on its inner surface, thereby making it difficult for cells to attach thereto. Blood conduits include tubular blood flow paths used in artificial blood vessels, catheters, shunts (used to lead blood out of the body), dialysis-type artificial kidneys, membrane-type oxygenators, artificial hearts, etc. It is. (b) Description of the prior art Conventionally, blood conduits have been made using synthetic polymer materials such as silicone rubber, polyurethane, and tetrafluoroethylene. Cells adhere, ie, a blood clot forms, obstructing blood flow. Therefore, materials to which cells do not adhere are required for blood conduits. (c) Object of the Invention The object of the present invention is to solve the above problem by providing a blood conduit with less cell adhesion by using an amino acid polymer containing leucine. (d) Structure of the Invention The present inventor has conducted various studies on materials that have properties that prevent cells from adhering to them, and has found that amino acid polymers containing leucine have properties that prevent cells from adhering to a large extent, and that they can be used as blood conduits. The present inventors have found that this is suitable and have completed the present invention. That is, the blood conduit of the present invention can be obtained by molding a leucine-containing amino acid polymer into a desired tube shape, or it can be obtained by molding an amino acid polymer containing leucine into a tube shape in advance, or it can be obtained by molding an amino acid polymer containing leucine into a tube shape in advance, and then molding the leucine-containing amino acid polymer onto the inner surface of the tube. Obtained by applying coalescence. Leucine as the constituent material of the amino acid polymer of the present invention and the amino acid as its copolymer component are D
Other amino acids include alanine, glycine, methionine, valine,
Glutamic acid derivatives, aspartic acid derivatives, lysine derivatives, ornithine derivatives, etc. are used. The molecular weight of the amino acid polymer is sufficient as long as it forms a film, and the leucine content in the polymer varies depending on the type of amino acid, but is preferably 30 mol% or more. (e) Examples of the invention Next, the present invention will be explained in more detail using examples. Example 1 A copolymer of L-leucine and benzyl L-glutamate (molar ratio of leucine and benzyl glutamate = 7:3) with benzene and dioxane (7:3).
A mixed solution of 3) was cast on a glass plate and air-dried to obtain a film (film thickness approximately 0.05 mm). This film was subjected to Soxhlet extraction with ethanol and then dried. A culture solution containing human-derived epithelial cells (approximately 100,000 cells/ml) was left in contact with this film in a room at 37°C with a carbon dioxide concentration of 5% and humidity of 100%.
After 17 hours, the film was lightly washed 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 a benzyl glutamate homopolymer film, silicone rubber used for blood conduits, 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−ロイシンとＬ−グルタミン酸ベンジルとの
共重合体のかわりに、Ｌ−ロイシンとＬ−カルボ
ベンゾキシリジンとの共重合体（ロイシンとカル
ボベンゾキシリジンとのモル比＝７：３）を用い
た以外は実施例１と同様にして、皮膜を成型し、
細胞付着実験を行つた。結果を第２表に示す。[Table] Example 2 Instead of the copolymer of L-leucine and benzyl L-glutamate, a copolymer of L-leucine and L-carbobenzoxylidine (molar ratio of leucine and carbobenzoxylidine = A film was molded in the same manner as in Example 1 except that 7:3) was used,
Cell adhesion experiments were performed. The results are shown in Table 2.
【表】
実施例 ３
ガラス管の内表面にロイシン含有アミノ酸重合
体を塗布し、乾燥後ガラス管からはずし、管状物
を得た。
実施例 ４
Ｌ−ロイシンとＬ−グルタミン酸ベンジルとの
共重合体において、それぞれのモル比が85：15、
50：50、30：70のものを実施例１と同様の方法で
皮膜を得た。
実施例 ５
Ｌ−ロイシンとＬ−カルボベンゾキシリジンと
の共重合体において、それぞれのモル比が85：
15、50：50、30：70のものを実施例１と同様の方
法で皮膜を得た。
実施例 ６
ポリ−Ｌ−ロイシンを熱ベンゼンに溶解し、実
施例１と同様にして皮膜を得た。
実施例 ７
Ｌ−ロイシンとＬ−グルタミン酸ベンジルとか
ら成るブロツク共重合体を、Ｎ−カルボキシアミ
ノ酸無水物法により合成した（このブロツク共重
合体の組成は、（グルタミン酸ベンジル（18％））
−（ロイシン（64％））−（グルタミン酸ベンジル
（18％））であつた。）。この共重合体を熱ベンゼン
に溶解し、実施例１と同様にして皮膜を得た。
実施例 ８
Ｌ−グルタミン酸ベンジルの代わりにＬ−カル
ボベンゾキシリジンを用い、以下実施例７と同様
にして、ブロツク共重合体皮膜を得た。
(f) 発明の効果
本発明は以上説明したように、細胞付着性の少
ないことを必要とする血液導管において、ロイシ
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、この血液導管を
任意の形状で得ることが可能である。[Table] Example 3 A leucine-containing amino acid polymer was applied to the inner surface of a glass tube, and after drying, it was removed from the glass tube to obtain a tubular product. Example 4 In a copolymer of L-leucine and benzyl L-glutamate, the molar ratio of each is 85:15,
Films of 50:50 and 30:70 were obtained in the same manner as in Example 1. Example 5 In a copolymer of L-leucine and L-carbobenzoxylidine, the molar ratio of each is 85:
15, 50:50, and 30:70 were obtained in the same manner as in Example 1. Example 6 Poly-L-leucine was dissolved in hot benzene and a film was obtained in the same manner as in Example 1. Example 7 A block copolymer consisting of L-leucine and benzyl L-glutamate was synthesized by the N-carboxyamino acid anhydride method (the composition of this block copolymer was (benzyl glutamate (18%)).
-(leucine (64%)) -(benzyl glutamate (18%)). ). This copolymer was dissolved in hot benzene, and a film was obtained in the same manner as in Example 1. Example 8 A block copolymer film was obtained in the same manner as in Example 7 except that L-carbobenzoxylidine was used in place of benzyl L-glutamate. (f) Effect of the invention As explained above, the present invention suppresses cell adhesion by molding an amino acid polymer containing leucine on the inner surface of a blood conduit that requires low cell adhesion. , it is possible to obtain this blood conduit in any shape.
Claims (1)
する血液導管。1 A blood conduit having an amino acid polymer containing leucine on its inner surface.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59133954A JPS6113953A (en) | 1984-06-28 | 1984-06-28 | Blood conduit |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59133954A JPS6113953A (en) | 1984-06-28 | 1984-06-28 | Blood conduit |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6113953A JPS6113953A (en) | 1986-01-22 |
| JPS644470B2 true JPS644470B2 (en) | 1989-01-25 |
Family
ID=15116958
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59133954A Granted JPS6113953A (en) | 1984-06-28 | 1984-06-28 | Blood conduit |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6113953A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0632298Y2 (en) * | 1989-06-08 | 1994-08-24 | 株式会社熊谷組 | Wall adsorption and cleaning device |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59133953A (en) * | 1983-01-18 | 1984-08-01 | Kobe Steel Ltd | Connecting method of feed nozzle and tundish in horizontal continuous casting device |
-
1984
- 1984-06-28 JP JP59133954A patent/JPS6113953A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6113953A (en) | 1986-01-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EXPY | Cancellation because of completion of term |