JPH0197472A - Multistage plasma separation method - Google Patents
Multistage plasma separation methodInfo
- Publication number
- JPH0197472A JPH0197472A JP11173187A JP11173187A JPH0197472A JP H0197472 A JPH0197472 A JP H0197472A JP 11173187 A JP11173187 A JP 11173187A JP 11173187 A JP11173187 A JP 11173187A JP H0197472 A JPH0197472 A JP H0197472A
- Authority
- JP
- Japan
- Prior art keywords
- albumin
- plasma
- separation membrane
- plasma separator
- separator
- 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.)
- Pending
Links
- 238000000926 separation method Methods 0.000 title claims abstract description 37
- 102000009027 Albumins Human genes 0.000 claims abstract description 45
- 108010088751 Albumins Proteins 0.000 claims abstract description 45
- 239000012528 membrane Substances 0.000 claims abstract description 28
- 239000011248 coating agent Substances 0.000 claims abstract description 7
- 238000000576 coating method Methods 0.000 claims abstract description 6
- 239000008280 blood Substances 0.000 claims description 6
- 210000004369 blood Anatomy 0.000 claims description 6
- 102000004169 proteins and genes Human genes 0.000 abstract description 4
- 108090000623 proteins and genes Proteins 0.000 abstract description 4
- 239000012510 hollow fiber Substances 0.000 description 9
- 241000282465 Canis Species 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 230000035699 permeability Effects 0.000 description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- -1 polypropylene Polymers 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 229920000098 polyolefin Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 206010018910 Haemolysis Diseases 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
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 230000008081 blood perfusion Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- DNTNDFLIKUKKOC-UHFFFAOYSA-N gabexate methanesulfonate Chemical compound CS([O-])(=O)=O.CCOC(=O)C1=CC=C(OC(=O)CCCCCN=C(N)[NH3+])C=C1 DNTNDFLIKUKKOC-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 229920001903 high density polyethylene Polymers 0.000 description 1
- 239000004700 high-density polyethylene Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 238000002616 plasmapheresis Methods 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 229920002239 polyacrylonitrile Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920000306 polymethylpentene Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
Landscapes
- External Artificial Organs (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、アルブミンの透過率を増大させるための多段
式血漿分離法に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a multistage plasma separation method for increasing the permeability of albumin.
［従来の技術］
近年、難治性疾患の血漿交換療法が臨床応用され効果を
挙げつつある。しかしながら、この血漿交換療法におい
ては血漿成分を全て除去し、新鮮血漿、アルブミン等を
補充するもので、血漿中の有効成分を回収できず、しか
も血清肝炎など疾患の発生の問題が指摘されている。[Prior Art] In recent years, plasmapheresis therapy for intractable diseases has been clinically applied and is becoming effective. However, in this plasma exchange therapy, all plasma components are removed and fresh plasma, albumin, etc. are replenished, and the active components in the plasma cannot be recovered, and furthermore, problems have been pointed out regarding the occurrence of diseases such as serum hepatitis. .
そこで血漿から膜分離などにより疾患の原因となる物質
を除去せんとして二重濾過血漿分離法が提案されている
。Therefore, a double filtration plasma separation method has been proposed in order to remove disease-causing substances from plasma by membrane separation or the like.
この二重濾過血漿分離法は、第１段の血漿分離器で血液
から血漿成分のみを分離し、次いで第２段の血漿分離器
で、前記の分離された血漿成分のうち有益な成分（アル
ブミン）を再分離し、患者へ返すものである。In this double filtration plasma separation method, only plasma components are separated from blood in the first stage plasma separator, and then in the second stage plasma separator, useful components (albumin ) is reseparated and returned to the patient.
［発明が解決しようとする問題点］
しかしながら、このような従来の二重濾過血漿分離法に
あっては、アルブミンの透過率が最大でも０．７程度と
低く、またアルブミンの透過率を上昇させると、アルブ
ミン以外の蛋白質の透過率が増大するという欠点があっ
た。[Problems to be solved by the invention] However, in such a conventional double filtration plasma separation method, the albumin permeability is as low as about 0.7 at maximum, and the albumin permeability increases. However, there was a drawback that the permeability of proteins other than albumin increased.
［問題点を解決するための手段］
そこで本発明では、上記問題点を解決するため、第２段
の血漿分離器における分離操作において予めアルブミン
を分離膜に流通させて親アルブミン性を高めることによ
り、アルブミンの透過率を増大できるのではないかと着
想し、本発明に到達した。本発明によれば、第１の血漿
分離器において血液より血漿成分のみを分離し、次いで
第２の血漿分離器において、該第１の血漿分離器で分離
された血漿のうちアルブミンを再分離して返送する多段
式血漿分離法において、前記第２の血漿分離器における
アルブミンの再分離操作の前に、第２の血漿分離器の分
離膜に対し予めアルブミンによるコーティングを施すこ
とを特徴とする多段式血漿分離法、が提供される。[Means for Solving the Problems] Therefore, in the present invention, in order to solve the above problems, albumin is circulated through the separation membrane in advance in the separation operation in the second stage plasma separator to increase albumin affinity. The present invention was conceived based on the idea that the permeability of albumin could be increased. According to the present invention, only plasma components are separated from blood in the first plasma separator, and then, in the second plasma separator, albumin is reseparated from the plasma separated by the first plasma separator. In the multi-stage plasma separation method, the separation membrane of the second plasma separator is coated with albumin in advance before the albumin re-separation operation in the second plasma separator. A plasma separation method is provided.
本発明では、第２段目の血漿分離器における分離操作に
おいて、予めアルブミンを分離膜に流通させてコーティ
ングし、親アルブミン性を高めることにその特徴を有す
るものである。ここで、分離膜コーティングに使用する
アルブミンとしては、特に患者自身のものが好ましい。The present invention is characterized in that in the separation operation in the second-stage plasma separator, albumin is passed through the separation membrane in advance to coat it, thereby increasing albumin affinity. Here, the albumin used for the separation membrane coating is preferably the patient's own albumin.
市販のアルブミンを使用する場合、患者に対しては非自
己の蛋白質であり、場合によっては抗原抗体反応が起こ
る可能性があるからである。This is because when commercially available albumin is used, it is a non-self protein for the patient, and an antigen-antibody reaction may occur depending on the case.
また、本発明においては、血漿採取の実施に当り、血液
の抗凝固剤を適量使用する必要がある。Further, in the present invention, it is necessary to use an appropriate amount of a blood anticoagulant when collecting plasma.
抗凝固剤としては体外血液潅流に使用できるものであれ
ばいずれでもよく、例えば、クエン酸（ＡＣＤ、ＣＰＤ
等）、ヘパリン、プロスタグランジン、ＦＯＹ、ＭＤ−
８０５等が使用される。これらはその特性により献血者
へ注射によって投与することもできる他、送血ラインに
分枝な設け、そこから持続投与器あるいは点滴で投与す
ることも可能である。Any anticoagulant that can be used for extracorporeal blood perfusion may be used, such as citric acid (ACD, CPD).
etc.), heparin, prostaglandin, FOY, MD-
805 etc. are used. Depending on their properties, they can be administered to blood donors by injection, or they can also be provided as a branch in the blood supply line and administered from there via a continuous injector or drip.
また、血漿分離器としては、血漿分離速度が大で、血漿
蛋白質の透過性が良好ないずれの模型血漿分離器も使用
可能であり、中空糸膜型の分離膜モジュールを使用する
ことが好ましい。Further, as the plasma separator, any model plasma separator that has a high plasma separation rate and good plasma protein permeability can be used, and it is preferable to use a hollow fiber membrane type separation membrane module.
血漿分離膜モジュールに用いられる中空糸膜としては、
親水性を有するものが好ましく用いられるが、他方、元
来は疎水性であっても、界面活性剤又はコーティング剤
等により親水化処理したものも好ましく使用できる。更
に、疎水性の中空糸膜を水と相溶性がよく表面張力の小
さい、例えばアルコールの如き物質によって洗浄し、生
理食塩水のような無菌水、無塵水にて充填しておき、使
用に際して血液と置換することによって本発明の中空糸
膜として用いることができる。Hollow fiber membranes used in plasma separation membrane modules include:
Those having hydrophilic properties are preferably used, but on the other hand, even if they are originally hydrophobic, those that have been treated to become hydrophilic with a surfactant or a coating agent can also be preferably used. Furthermore, the hydrophobic hollow fiber membrane is washed with a substance that is highly compatible with water and has a low surface tension, such as alcohol, and is filled with sterile water such as physiological saline or dust-free water, and before use. It can be used as the hollow fiber membrane of the present invention by replacing it with blood.
また、中空糸の材質としては特に制限されるものではな
い。高分子材料を素材とするものの例としては、ポリオ
レフィン（高密度ポリエチレン、ポリプロピレン、ポリ
（４−メチル−ペンテン−１）など）、フッ素含有高分
子化合物、ポリスルホン、ポリカーボネート、ポリ塩化
ビニル、セルロースアセテート、ポリアクリロニトリル
、ポリビニルアルコール、ポリメチルメタアクリレート
、ポリアミド等の多孔質中空糸を挙げることができる。Further, the material of the hollow fibers is not particularly limited. Examples of polymer materials include polyolefins (high-density polyethylene, polypropylene, poly(4-methyl-pentene-1), etc.), fluorine-containing polymer compounds, polysulfone, polycarbonate, polyvinyl chloride, cellulose acetate, Examples include porous hollow fibers such as polyacrylonitrile, polyvinyl alcohol, polymethyl methacrylate, and polyamide.
また無機材料を素材とするものの例としては、ガラス、
セラミックス、炭素等の多孔質中空糸を挙げることがで
きる。以上のうち、耐溶血性か高い点から、ポリオレフ
ィンを素材とする膜が好ましい。多孔質中空糸の外径、
周壁部厚さ、孔径も特に制限されるものではないが、一
般には外径が約１０〜約１０００−■、周壁部厚さが約
１０〜約５００１Ｌｍ 、孔径が約０．０１〜約７ ｐ
−ｍのものが好ましい。Examples of materials made from inorganic materials include glass,
Examples include porous hollow fibers made of ceramics, carbon, and the like. Among the above, membranes made of polyolefin are preferred from the viewpoint of high hemolysis resistance. Outer diameter of porous hollow fiber,
The thickness of the peripheral wall and the diameter of the hole are not particularly limited, but generally the outer diameter is about 10 to about 1,000 mm, the thickness of the peripheral wall is about 10 to about 5,001 Lm, and the hole diameter is about 0.01 to about 7 p.
-m is preferred.
［実施例］
以下、本発明を実施例に基き詳細に説明するが、本発明
が実施例に限られるものでないことは明らかであろう。[Examples] Hereinafter, the present invention will be described in detail based on Examples, but it will be clear that the present invention is not limited to the Examples.
（実施例１）
イヌ新鮮血漿ならびにイヌアルブミンを使用し、アルブ
ミン未処理分離膜（従来例）とアルブミン処理分離膜（
実施例）の２種類について透過実験を実施し、アルブミ
ンおよび総蛋白質の濾過率（篩い係数、Ｓ、Ｃ，）を比
較検討した。尚、実験には図面に示す回路を使用した。(Example 1) Using fresh canine plasma and canine albumin, an albumin-untreated separation membrane (conventional example) and an albumin-treated separation membrane (conventional example) were used.
A permeation experiment was conducted on two types of samples (Example), and the filtration rates (sieving coefficients, S, C,) of albumin and total protein were compared and examined. Note that the circuit shown in the drawing was used in the experiment.
図面において、ｌは第２の血漿分離器、２はイヌアルブ
ミンの貯蔵タンク、３はイヌ血漿の貯蔵タンク、４は加
熱器、５および６はポンプで、■１〜■３は三方活栓で
ある。In the drawing, l is a second plasma separator, 2 is a canine albumin storage tank, 3 is a canine plasma storage tank, 4 is a heater, 5 and 6 are pumps, and ■1 to ■3 are three-way stopcocks. .
尚、第２の血漿分離器ｌの分離膜としては、ポリプロピ
レン製中空糸膜（宇部興産−製、膜孔径０．０４ＩＬｍ
、外径３００ ｐ−ｍ、内径２００＃Ｌｍ、空隙率５５
％）を使用した。The separation membrane of the second plasma separator 1 was a polypropylene hollow fiber membrane (made by Ube Industries, Ltd., membrane pore size 0.04ILm).
, outer diameter 300 p-m, inner diameter 200#Lm, porosity 55
%)It was used.
以上の構成て、第１の血漿分離器（図示せず）の分離膜
により得られたイヌ血漿を第２のｍ漿分離器ｌにより濾
過した。従来法では三方活栓ｖ２を閉鎖し、Ｖ、、Ｖ３
を開放してポンプ５による血漿流量Ｑ Ｆ ｓが３０ｍ
文／ｗｉｎ、ポンプ６による血漿流量ＱＰ２が１５ｍＭ
／■ｉｎの条件下において２次濾過を行った。一方、ア
ルブミンコーティングを施す本発明の実施例ては、三方
活栓Ｖ１．Ｖ３を閉鎖し、ｖ２を開放して約５０１見の
イヌアルブミンを予め第２の血漿分離器ｌの分離膜に流
通させた後、三方活栓Ｖ、、Ｖ、を開放し、ｖ２を閉鎖
して、従来法と同一の条件下で２次濾過を実施した。With the above configuration, dog plasma obtained by the separation membrane of the first plasma separator (not shown) was filtered by the second plasma separator. In the conventional method, three-way stopcock v2 is closed and V, , V3
is opened and the plasma flow rate Q F s by pump 5 is 30 m
Text/win, plasma flow rate QP2 by pump 6 is 15mM
Secondary filtration was performed under the condition of /■in. On the other hand, in the embodiment of the present invention in which albumin coating is applied, the three-way stopcock V1. After closing V3 and opening v2 to allow approximately 501 g of canine albumin to flow through the separation membrane of the second plasma separator l, the three-way stopcocks V, , V are opened and v2 is closed. , secondary filtration was performed under the same conditions as the conventional method.
その結果、アルブミンコーティングを施した本発明の実
施例ては、従来法に比しアルブミン濾過率が向上し、実
質的に有意なものであることが分った。表１に結果を示
す。As a result, it was found that the albumin filtration rate of the embodiment of the present invention in which albumin coating was applied was substantially improved compared to the conventional method. Table 1 shows the results.
表 １
［発明の効果］
以上説明したように、本発明の多段式血漿分離法によれ
ば、予めアルブミンを分離膜に流通させてコーティング
し、親アルブミン性を高めているので、アルブミンの透
過率を増大させることができるという利点を有する。Table 1 [Effects of the Invention] As explained above, according to the multistage plasma separation method of the present invention, albumin is passed through the separation membrane and coated in advance to increase the albumin affinity, so that the albumin permeability decreases. It has the advantage of being able to increase the
図面は第２段の血漿分離操作を行なうための回路を示す
説明図である。
１・・・第２の血漿分離器、２・・・イヌアルブミンの
貯蔵タンク、３・・・イヌ血漿の貯蔵タンク、４・・・
加熱器、５，６・・・ポンプ、■１〜ｖ３・・・三方活
栓。The drawing is an explanatory diagram showing a circuit for performing the second stage plasma separation operation. 1... Second plasma separator, 2... Canine albumin storage tank, 3... Canine plasma storage tank, 4...
Heater, 5, 6...pump, ■1~v3...three-way stopcock.
Claims (2)
を分離し、次いで第２の血漿分離器において、該第１の
血漿分離器で分離された血漿のうちアルブミンを再分離
して返送する多段式血漿分離法において、前記第２の血
漿分離器におけるアルブミンの再分離操作の前に、第２
の血漿分離器の分離膜に対し予めアルブミンによるコー
ティングを施すことを特徴とする多段式血漿分離法。(1) Only plasma components are separated from blood in a first plasma separator, and then in a second plasma separator, albumin is reseparated from the plasma separated by the first plasma separator and returned. In the multistage plasma separation method, before the albumin reseparation operation in the second plasma separator, a second
A multistage plasma separation method characterized by coating the separation membrane of a plasma separator with albumin in advance.
ミンである特許請求の範囲第１項記載の多段式血漿分離
法。(2) The multistage plasma separation method according to claim 1, wherein the albumin to be coated is the patient's own albumin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11173187A JPH0197472A (en) | 1987-05-08 | 1987-05-08 | Multistage plasma separation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11173187A JPH0197472A (en) | 1987-05-08 | 1987-05-08 | Multistage plasma separation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0197472A true JPH0197472A (en) | 1989-04-14 |
Family
ID=14568748
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11173187A Pending JPH0197472A (en) | 1987-05-08 | 1987-05-08 | Multistage plasma separation method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0197472A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009291498A (en) * | 2008-06-06 | 2009-12-17 | Nipro Corp | Hollow fiber membrane and extracorporeal circulation module |
-
1987
- 1987-05-08 JP JP11173187A patent/JPH0197472A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009291498A (en) * | 2008-06-06 | 2009-12-17 | Nipro Corp | Hollow fiber membrane and extracorporeal circulation module |
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