JPH04314456A - Blood treating apparatus and method for treating plasma - Google Patents
Blood treating apparatus and method for treating plasmaInfo
- Publication number
- JPH04314456A JPH04314456A JP3067544A JP6754491A JPH04314456A JP H04314456 A JPH04314456 A JP H04314456A JP 3067544 A JP3067544 A JP 3067544A JP 6754491 A JP6754491 A JP 6754491A JP H04314456 A JPH04314456 A JP H04314456A
- Authority
- JP
- Japan
- Prior art keywords
- blood
- adsorption
- processing device
- ldl
- plasma
- 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
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- 239000008280 blood Substances 0.000 title claims abstract description 93
- 238000000034 method Methods 0.000 title description 24
- 238000001179 sorption measurement Methods 0.000 claims abstract description 74
- 108010007622 LDL Lipoproteins Proteins 0.000 claims description 47
- 102000007330 LDL Lipoproteins Human genes 0.000 claims description 47
- 239000000126 substance Substances 0.000 claims description 45
- 238000012545 processing Methods 0.000 claims description 39
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- 238000003672 processing method Methods 0.000 claims description 4
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- 239000000835 fiber Substances 0.000 abstract description 36
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 26
- 229910002804 graphite Inorganic materials 0.000 abstract description 25
- 239000010439 graphite Substances 0.000 abstract description 25
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 abstract description 8
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Abstract
Description
【０００１】0001
【産業上の利用分野】本発明は血液処理装置および処理
方法に関する。詳細には、血液中の特性の成分を選択的
に吸着して分離するための血液処理装置および処理方法
であり、本発明の装置および方法は、血液中の低密度リ
ポ蛋白質を選択的に吸着除去して血液を浄化するのに特
に適している。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a blood processing apparatus and a blood processing method. Specifically, it is a blood processing device and a processing method for selectively adsorbing and separating characteristic components in blood, and the device and method of the present invention selectively adsorb low-density lipoproteins in blood. Particularly suitable for removing and purifying blood.
【０００２】0002
【従来の技術】虚血性心疾患や各種血管障害、更には単
状糸球体硬化症由来の薬物抵抗性ネフローゼを惹起する
病因物質とされているコレステロールは、水に対して難
溶性であるため、トリグリセライド、リン脂質、アポ蛋
白質等とリポ蛋白質粒子を形成し、血中に存在している
。これらのリポ蛋白質は、その密度によってそれぞれ、
超低密度リポ蛋白質（ＶＬＤＬ Ｖｅｒｙ Ｌｏｗ
Ｄｅｎｓｉｔｙ Ｌｉｐｏｐｒｏｔｅｉｎ）、低密度リ
ポ蛋白質（ＬＤＬ Ｌｏｗ Ｄｅｎｓｉｔｙ Ｌｉｐ
ｏｐｒｏｔｅｉｎ）、高密度リポ蛋白質（ＨＤＬ Ｈ
ｉｇｈ Ｄｅｎｓｉｔｙ Ｌｉｐｏｐｒｏｔｅｉｎ）な
どに分類されるが、特にＬＤＬはコレステロールを多く
含む。[Prior Art] Cholesterol, which is thought to be the causative agent of ischemic heart disease, various vascular disorders, and even drug-resistant nephrosis derived from uniform glomerulosclerosis, is sparingly soluble in water. It forms lipoprotein particles with triglycerides, phospholipids, apoproteins, etc., and exists in the blood. Depending on their density, these lipoproteins are
Very low density lipoprotein (VLDL)
Density Lipoprotein), Low Density Lipoprotein (LDL Low Density Lip
oprotein), high-density lipoprotein (HDL H
In particular, LDL contains a large amount of cholesterol.
【０００３】このＬＤＬは、正常人では肝臓における血
漿リポ蛋白質の代謝によって、定常値に維持されるが、
遺伝的に肝臓にＬＤＬレセプターを有さない家族性高コ
レステロール血症は、ＬＤＬの異常な増加により若年性
虚血性疾患等を惹起する。家族性高コレステロール血症
の特にホモ接合体と重症のヘテロ接合体では、薬物療法
によってコレステロール濃度を動脈硬化の進展を防止し
えるレベルまで低下させることは困難であるので、場合
によっては、体外におけるさらなる血液浄化処理が必要
とされる。[0003] In normal people, LDL is maintained at a steady level by the metabolism of plasma lipoproteins in the liver;
Familial hypercholesterolemia, in which the liver does not have LDL receptors, causes juvenile ischemic disease and the like due to an abnormal increase in LDL. Especially in homozygotes and severe heterozygotes with familial hypercholesterolemia, it is difficult to lower the cholesterol concentration with drug therapy to a level that can prevent the progression of arteriosclerosis. Further blood purification treatment is required.
【０００４】このようなＬＤＬ除去を目的とする血漿浄
化法として、連続遠心分離と凍結血漿を用いた血漿交換
療法がトンプソンらによって試みられ、血中のＬＤＬ濃
度の減少に起因する高い臨床効果が確認された（Ｔｏｍ
ｐｓｏｎ，Ｇ．Ｒ．，ｅｔ． ａｌ；Ｐｌａｓｍａ ｅ
ｘｃｈａｎｇｅ ｉｎ ｔｈｅ ｍａｎｅｇｅｍｅｎｔ
ｏｆ ｈｏｍｏｚｔｇｏｕｓ ｆａｍｉｌｉａｌｈｙ
ｐｅｒｃｈｏｌｅｓｔｅｒｏｌａｃｍｉａ． Ｌａｎｃ
ｅｔ １、 １２０８、 １９７５）。しかしながら、
この方法では、複雑かつ高価な装置を必要とする上、遠
心分離処理によって血漿中の他の有用成分まで根こそぎ
捨てられてしまうものであった。[0004] As a plasma purification method for the purpose of removing LDL, continuous centrifugation and plasmapheresis using frozen plasma were attempted by Thompson et al. Confirmed (Tom
pson, G. R. , etc. al;Plasma e
xchange in the management
of homoztgous family
percholesterolacmia. Lanc
et 1, 1208, 1975). however,
This method requires complicated and expensive equipment, and in addition, other useful components in the plasma are completely discarded by the centrifugation process.
【０００５】このような観点から、さらに精度の高い選
択的ＬＤＬ除去法として、膜濾過法、分別沈殿法および
選択的吸着法の３つに大別される種々の方法が提唱され
た。しかしながら、これらの方法においても多くの問題
点が残されているものであった。例えば、膜濾過法であ
るダブルフィルトレーションプラズマフェレーシスでは
、分子サイズによるＬＤＬとＨＤＬの分画化が不完全で
あり、遊離コレステロールを取り込み、高コレステロー
ル血症の抑制因子と推定されＨＤＬや各種有用血漿蛋白
質を損失してしまうものであった。[0005] From this viewpoint, various methods have been proposed as more accurate selective LDL removal methods, which can be broadly classified into three types: membrane filtration, fractional precipitation, and selective adsorption. However, many problems remain in these methods as well. For example, in double filtration plasmapheresis, which is a membrane filtration method, the fractionation of LDL and HDL based on molecular size is incomplete, and free cholesterol is taken in, which is thought to be an inhibitory factor for hypercholesterolemia. This resulted in the loss of useful plasma proteins.
【０００６】また、分別沈殿法であるヘパリン−カルシ
ウム沈殿法は、ＬＤＬに対して選択的であるが、除去量
に問題があり、生理的濃度の約１０倍程度のカルシウム
の使用を余儀なくされるものであった。さらに、選択的
吸着法では、除去能力に問題があり、またリガンドを使
用する場合には、リガンドの脱離による安全性や性能の
安定性が危惧されるものであった。特に、リガンドとし
て抗ＬＤＬ抗体や酸性ムコ多糖を固定化する場合には、
経済性の面に問題が生じてくるものであり、これらの点
から、選択吸着法も完成された実用的な技術とはいえな
いものであった。[0006] Furthermore, although the heparin-calcium precipitation method, which is a fractional precipitation method, is selective for LDL, there is a problem in the amount of removal, and it is necessary to use calcium at about 10 times the physiological concentration. It was something. Furthermore, the selective adsorption method has a problem in removal ability, and when a ligand is used, there are concerns about safety and stability of performance due to desorption of the ligand. In particular, when immobilizing anti-LDL antibodies or acidic mucopolysaccharides as ligands,
Problems arise in terms of economic efficiency, and from these points of view, the selective adsorption method cannot be called a completed practical technology.
【０００７】上記事情に鑑み、本願出願人は、先に血液
中の不用物を選択的に吸着除去する血漿処理装置であっ
て、電気的に分極させた固体表面を有する吸着担体を使
用することを特徴とする血漿処理装置を提供している（
特願平１−２５４０３３号）。この血漿処理装置は、Ｌ
ＤＬ等の静電的に異方性の高い分子構造を有する不用物
を静電的相互作用によって極めて選択的に吸着除去する
ことができるものである。したがって、本装置によれば
、ＬＤＬに対して選択性が高いので、高コレステロール
血症の抑制因子と推定されるＨＤＬや各種有用血漿蛋白
質を損失する虞れが少なく、また静電的相互作用によっ
て吸着するので、リガンドを必要とせず、安全性に優れ
るものであった。また静電気作用を機械的に任意にコン
トロールすることが可能であるため、ＬＤＬのみならず
、吸着対象をマルチ化することも容易であり、さらには
測定対象である血液の個体差に併せて、吸着体表面の電
気的環境を制御することもできる等の利点があった。[0007] In view of the above circumstances, the applicant proposed a plasma processing device that selectively adsorbs and removes unnecessary substances from blood, using an adsorption carrier having an electrically polarized solid surface. We provide plasma processing equipment featuring (
(Patent Application No. 1-254033). This plasma processing device is
It is possible to very selectively adsorb and remove unwanted substances such as DL having a highly electrostatically anisotropic molecular structure through electrostatic interaction. Therefore, since this device has high selectivity for LDL, there is little risk of losing HDL and various useful plasma proteins, which are estimated to be inhibitors of hypercholesterolemia, and Since it adsorbs, it does not require a ligand and has excellent safety. In addition, since the electrostatic effect can be mechanically controlled arbitrarily, it is easy to adsorb not only LDL but also multiple adsorption targets. It had the advantage of being able to control the electrical environment on the body surface.
【０００８】[0008]
【発明が解決しようとする課題】上述したように、上記
の血漿処理装置においても、十分なＬＤＬ等の不用物の
吸着除去効果を有するが、本発明は、上記の血漿処理装
置を改良することにより、さらに高いＬＤＬ等の不用物
に対する選択性を有する血液処理装置を提供することを
目的とするものである。[Problems to be Solved by the Invention] As mentioned above, the plasma processing device described above also has a sufficient effect of adsorbing and removing unnecessary substances such as LDL, but the present invention aims to improve the plasma processing device described above. Accordingly, it is an object of the present invention to provide a blood processing device that has even higher selectivity for unnecessary substances such as LDL.
【０００９】[0009]
【課題を解決するための手段】上記の課題は、血液中の
特定成分を選択的に吸着しえる吸着担体を備えた血液処
理装置であって、前記吸着担体は、電気的に分極された
固体表面を有し、かつ当該固体表面には吸着補助物質が
付与されてなることを特徴とする血液処理装置によって
達成される。[Means for Solving the Problems] The above object is a blood processing device equipped with an adsorption carrier capable of selectively adsorbing specific components in blood, wherein the adsorption carrier is an electrically polarized solid state. This is achieved by a blood processing device having a solid surface, and an adsorption auxiliary substance is applied to the solid surface.
【００１０】また、本発明は、前記血液処理装置が血液
浄化器であり、前記特定成分が低密度リポ蛋白質である
血液処理装置を示すものである。前記吸着補助物質は、
解離基を有する高分子物質であるのが好ましく、特に酸
性基を有する高分子物質であるのが好ましい。酸性基を
有する高分子物質は、硫酸基および／またはカルボン酸
基を有する高分子物質であるのが好ましい。The present invention also provides a blood processing device, wherein the blood processing device is a blood purifier, and the specific component is low density lipoprotein. The adsorption auxiliary substance is
A polymer substance having a dissociative group is preferable, and a polymer substance having an acidic group is particularly preferable. The polymeric substance having an acidic group is preferably a polymeric substance having a sulfuric acid group and/or a carboxylic acid group.
【００１１】また、本発明は、処理しようとする血液を
、電気的に分極された固体表面を有し、かつ当該固体表
面に吸着補助物質が付与されてなる吸着担体に接触させ
、静電的相互作用により血液中に含まれる静電的に異方
性の高い分子構造を有する不用物を選択的に吸着するこ
とを特徴とする血漿処理方法を示すものである。[0011] Furthermore, the present invention provides an electrostatic effect by bringing the blood to be treated into contact with an adsorption carrier having an electrically polarized solid surface and having an adsorption auxiliary substance applied to the solid surface. This is a plasma processing method characterized by selectively adsorbing waste substances contained in blood having a highly electrostatically anisotropic molecular structure through interaction.
【００１２】ここで、本発明でいう「血液」とは、全血
だけでなく、全血から血球成分を分離した血漿成分、血
清成分等を包含する。また、本発明における「吸着担体
は電気的に分極された固体表面を有し」とは、吸着担体
を電気機器や電気回路を使用して、その固体表面に電気
的な分極を生じさせた吸着担体をいい、その場合の「分
極」とは、２つの電極間に電圧を印加することによって
生じる電界によって、導電性または非導電性の固体表面
に形成される電気的極性の変化を意味する。電圧の印加
方法としては、電解質中で２つの電極間に直流電圧や交
流電圧を印加できるものであればどのようなものであっ
てもよく、電極そのものを含めた固体表面の電荷を何ら
かの方法で制御できればよい。[0012] Here, the term "blood" as used in the present invention includes not only whole blood, but also plasma components, serum components, etc. obtained by separating blood cell components from whole blood. In addition, in the present invention, "the adsorption carrier has an electrically polarized solid surface" means that the adsorption carrier is adsorbed using an electric device or an electric circuit to generate electrical polarization on the solid surface. "Polarization" refers to a carrier, in which case "polarization" refers to a change in electrical polarity formed on a conductive or non-conductive solid surface by an electric field generated by applying a voltage between two electrodes. The voltage application method may be any method as long as it can apply a DC voltage or an AC voltage between two electrodes in the electrolyte. It's good if you can control it.
【００１３】本発明で採用できる電気的分極について、
具体例を挙げて説明する。例えば、図１に示すように、
電解質１中で、電極２および電極３間に直流電場で直接
電流を流して物理的な力、すなわち電気泳動を発生させ
る方法がある。また、図２に示すように、電解質１中で
、一定の周波数以上の交流電場を電極２と電極３間に印
加することにより、電極の材質、電解質の種類、電場の
強さ、周波数等に応じて、電極２および電極３自体の界
面を分極させる方法がある。更に、図３に示すように、
電極２と電極３の間に絶縁体４（真空も含む）を挿入し
、絶縁体４の誘電率に応じた分極表面を得る方法、図４
に示すように、一定の基準電位を有する基準電極５およ
び対極７を用いて、作用極６と基準電極７との間の電位
を電解質１が電気分解しない範囲で電気化学的に制御す
る方法などがあり、場合によっては動磁場によって電流
を得ることもできる。Regarding electrical polarization that can be adopted in the present invention,
This will be explained using a specific example. For example, as shown in Figure 1,
There is a method of directly passing a current between electrodes 2 and 3 in an electrolyte 1 in a direct current electric field to generate physical force, that is, electrophoresis. In addition, as shown in Fig. 2, by applying an alternating current electric field of a certain frequency or higher between electrodes 2 and 3 in electrolyte 1, it is possible to change the electrode material, electrolyte type, electric field strength, frequency, etc. Accordingly, there is a method of polarizing the interfaces of the electrodes 2 and 3 themselves. Furthermore, as shown in Figure 3,
A method of inserting an insulator 4 (including a vacuum) between electrodes 2 and 3 and obtaining a polarized surface according to the dielectric constant of the insulator 4, FIG. 4
As shown in , a method of electrochemically controlling the potential between the working electrode 6 and the reference electrode 7 within a range in which the electrolyte 1 is not electrolyzed using a reference electrode 5 and a counter electrode 7 having a constant reference potential, etc. In some cases, it is also possible to obtain current using a dynamic magnetic field.
【００１４】上記方法のうちでも、電極それ自体や絶縁
体の固体表面を分極させる方法は、電気現象の変化（す
なわち系にかかるエネルギー）が、電極や絶縁体の固体
界面のごく近傍にのみ集約されるため、被吸着成分が吸
着時に受ける電気的な相互作用がより大きくなり、特定
の成分をより有利に選択的に吸着できる。特に、図４に
示したような電気化学的な制御方法は、電極そのものを
吸着担体として利用でき、しかも極めて低電圧、低エネ
ルギー系で電極固体表面に有効な電荷を設定できるので
好ましい。その場合に用いる電気機器や電気回路は、公
知の電解電池を構成するものと同様のものでよく、電極
電位の制御には例えば汎用のポテンシオスタットなどを
用いることが可能であり、また基準極や対極の接続に塩
橋を用いてもよい。Among the above methods, the method of polarizing the electrode itself or the solid surface of the insulator is such that the change in the electrical phenomenon (that is, the energy applied to the system) is concentrated only in the very vicinity of the solid interface of the electrode or insulator. Therefore, the electrical interaction that the adsorbed component receives during adsorption becomes larger, and a specific component can be more advantageously and selectively adsorbed. In particular, the electrochemical control method as shown in FIG. 4 is preferable because the electrode itself can be used as an adsorption carrier and an effective charge can be set on the solid surface of the electrode using an extremely low voltage and low energy system. The electrical equipment and circuitry used in this case may be the same as those constituting known electrolytic batteries; for example, a general-purpose potentiostat may be used to control the electrode potential; A salt bridge may be used to connect the electrode and the opposite electrode.
【００１５】基準極としては、銀／塩化銀電極や飽和カ
ロメル電極等が、また対極としては白金やカーボン等が
好適に用いられる。吸着担体ともなる作用極としては、
電解液中で分極性の高い素材を用いるのが好ましく、例
えば亜鉛、白金、金、炭素系の材料が好ましい。また、
酸化錫をドープした酸化インジウム等の半導体も作用極
として好適に使用可能である。更に、作用極の形状は特
に限定されないが、吸着面積を大きくするために、多孔
粒子、多孔質塊状物、発泡体、繊維状物等の多孔質構造
体の形態にしておくのがよく、繊維状物の場合は、繊維
の集合体、編織物または不織布等のいずれの形態であっ
てもよい。As the reference electrode, a silver/silver chloride electrode, a saturated calomel electrode, etc. are preferably used, and as the counter electrode, platinum, carbon, etc. are preferably used. As a working electrode that also serves as an adsorption carrier,
It is preferable to use a material that is highly polarizable in the electrolytic solution, such as zinc, platinum, gold, or carbon-based materials. Also,
Semiconductors such as indium oxide doped with tin oxide can also be suitably used as the working electrode. Further, the shape of the working electrode is not particularly limited, but in order to increase the adsorption area, it is preferably in the form of a porous structure such as porous particles, porous lumps, foams, or fibrous materials. In the case of a shaped article, it may be in any form such as an aggregate of fibers, a knitted fabric, or a nonwoven fabric.
【００１６】そして、上記のものが適当なハウジングに
収納されて電解電池の構成を有するものとなればよい。
そして、その場合のハウジングは、ポリエチレン、ポリ
プロピレン、ポリカーボネート、ポリスチレン、ポリメ
チルメタクリレート等の合成樹脂、ガラス、絶縁処理を
施したステンレス等の金属などから形成することが可能
であり、特にポリプロピレン、ポリカーボネート等が湿
熱滅菌が可能であり、取り扱いが容易で好ましい。この
ように、吸着担体の固体表面を電気的に分極させるよう
にした本発明では、分極のために使用する電気機器等の
出力等を変えることによって、同一の吸着担体を用いた
場合でも、その固体表面の電気的分極状態（すなわち静
電状態）を、吸着させようとする血液中の成分の種類や
荷電状態に応じて、任意に設定、変化することができ、
極めて便利である。[0016] The above-mentioned battery may be housed in a suitable housing to have the structure of an electrolytic battery. In this case, the housing can be made of synthetic resin such as polyethylene, polypropylene, polycarbonate, polystyrene, polymethyl methacrylate, glass, or metal such as stainless steel that has been subjected to insulation treatment, and in particular polypropylene, polycarbonate, etc. However, it is preferable because it can be sterilized with moist heat and is easy to handle. As described above, in the present invention, in which the solid surface of the adsorption carrier is electrically polarized, even when the same adsorption carrier is used, by changing the output etc. of the electrical equipment used for polarization. The electrical polarization state (i.e. electrostatic state) of the solid surface can be arbitrarily set and changed depending on the type and charge state of the blood components to be adsorbed.
Extremely convenient.
【００１７】更に、本発明では、電気的に分極させる吸
着担体の固体表面に、吸着保持物質が付与されているこ
とを必須にするものである。本発明では、吸着担体の電
気的分極による電気的吸引作用と、吸着補助物質の有す
るアンカリング効果によって、特定成分をより効率よく
選択的に吸着させ、血液から分離することができる。こ
の吸着補助物質は、血液中の被吸着成分（特定成分）と
反対の帯電状態にあるか、または血液中で吸着担体を電
気的に分極させて処理を行う際に、反対の帯電状態にな
り得る物質である。Furthermore, in the present invention, it is essential that an adsorption/retention substance be applied to the solid surface of the adsorption carrier to be electrically polarized. In the present invention, a specific component can be more efficiently and selectively adsorbed and separated from blood by the electric attraction effect caused by the electrical polarization of the adsorption carrier and the anchoring effect of the adsorption auxiliary substance. This adsorption auxiliary substance is in an oppositely charged state to the adsorbed component (specific component) in the blood, or becomes oppositely charged when processing is performed by electrically polarizing the adsorption carrier in the blood. It is a substance that can be obtained.
【００１８】例えば、被吸着成分がカチオン性の物質で
ある場合は、吸着補助物質をカチオンを静電的相互作用
によって吸引するアニオン性の物質としておくのがよく
、また反対に被吸着成分がアニオン性の物質である場合
は、吸着補助物質をカチオン性の物質としておくのがよ
い。特に、コレステロールを多量に含む上記したＬＤＬ
はカチオン性であるので、全血や血漿等の血液中からＬ
ＤＬを吸着分離する場合は、吸着担体に施す吸着補助物
質をアニオン性の物質から選ぶのがよい。For example, when the component to be adsorbed is a cationic substance, it is preferable to use an anionic substance that attracts cations by electrostatic interaction as the adsorption auxiliary substance; If the adsorption auxiliary substance is a cationic substance, it is preferable to use a cationic substance as the adsorption auxiliary substance. In particular, the above-mentioned LDL containing a large amount of cholesterol
Since it is cationic, L is removed from blood such as whole blood and plasma.
When DL is adsorbed and separated, the adsorption auxiliary substance applied to the adsorption carrier is preferably selected from anionic substances.
【００１９】吸着担体に施す吸着補助物質は、担体から
剥離したり、被処理血液中に溶解することなく吸着担体
に長期間安定して保持されることが必要であり、この点
からアニオン性またはカチオン性の極性基（官能基）を
豊富に有し、担体表面に固定化されたときに水不溶性と
なる重合体であるのが好ましい。そのような重合体の好
ましい例としては、上記したような極性基を有し、その
基本骨格が疎水性である、水不溶性のビニル系重合体ま
たは共重合体、ポリアミド、ポリイミド、ポリエステル
、ポリウレタン、ポリシロキサン等の合成樹脂および合
成ゴムを挙げることができる。それらのうちでも、エチ
レン、プロピレン、ブテン等のオレフィン類、スチレン
類、ブタジエン等のジエン類、塩化ビニル、酢酸ビニル
、アクリレート系モノマー、フッ化ビニル等のフッ素化
モノマー等のビニル系不飽和モノマーからなるアニオン
性またはカチオン性の極性基を導入した重合体および共
重合体やポリアミドが望ましい。The adsorption auxiliary substance applied to the adsorption carrier must be stably retained on the adsorption carrier for a long period of time without peeling off from the carrier or dissolving into the blood to be treated. From this point of view, anionic or It is preferable to use a polymer that has abundant cationic polar groups (functional groups) and becomes water-insoluble when immobilized on the carrier surface. Preferred examples of such polymers include water-insoluble vinyl polymers or copolymers, polyamides, polyimides, polyesters, polyurethanes, which have the above-mentioned polar groups and whose basic skeleton is hydrophobic. Synthetic resins such as polysiloxane and synthetic rubber can be mentioned. Among them, olefins such as ethylene, propylene, butene, styrenes, dienes such as butadiene, vinyl unsaturated monomers such as vinyl chloride, vinyl acetate, acrylate monomers, fluorinated monomers such as vinyl fluoride, etc. Polymers, copolymers, and polyamides into which anionic or cationic polar groups have been introduced are desirable.
【００２０】本発明では、被吸着成分の帯電状態や種類
等に応じて、吸着補助物質の種類を選択して使用するこ
とが必要である。特に、全血や血漿中のＬＤＬを吸着分
離するための吸着担体としては、硫酸基やカルボン酸基
等のアニオン性の解離基を導入した上記したようなビニ
ル系不飽和モノマーからなる重合体および共重合体、ポ
リアミド等の合成樹脂がＬＤＬの吸着分離能が高く望ま
しい。In the present invention, it is necessary to select and use the type of adsorption auxiliary substance depending on the charged state and type of the component to be adsorbed. In particular, as adsorption carriers for adsorbing and separating LDL in whole blood and plasma, polymers made of vinyl unsaturated monomers as described above into which anionic dissociative groups such as sulfate groups and carboxylic acid groups have been introduced, and Synthetic resins such as copolymers and polyamides are desirable because they have a high ability to adsorb and separate LDL.
【００２１】吸着担体に上記した吸着補助物質を付与す
るにあたっては、固体表面に吸着補助物質を均一に施す
ことができる方法であればいずれも採用でき、例えば噴
霧、浸漬（コーティング）、注入、塗布、加圧含浸等の
方法を挙げることができる。また、吸着補助物質が上記
したようなビニル系モノマーからなる重合体または共重
合体である場合は、極性基を有する該重合体または共重
合体を吸着担体の固体表面に直接付与しても、または極
性基のない重合体または共重合体を固体表面に付与した
後に、重合体または共重合体に適当な後処理を施して極
性基を導入しても、或いは吸着担体の存在下にビニル系
モノマーを重合させて、重合と同時にそれら重合体から
なる膜を固体表面上に形成させてもよい。[0021] In applying the above-mentioned adsorption auxiliary substance to the adsorption carrier, any method that can uniformly apply the adsorption auxiliary substance to the solid surface can be adopted, such as spraying, dipping (coating), injection, and application. , pressure impregnation, and the like. In addition, when the adsorption auxiliary substance is a polymer or copolymer made of vinyl monomers as described above, even if the polymer or copolymer having a polar group is directly applied to the solid surface of the adsorption carrier, Alternatively, after applying a polymer or copolymer without polar groups to the solid surface, the polymer or copolymer may be subjected to appropriate post-treatment to introduce polar groups, or vinyl-based polymers may be applied in the presence of an adsorption carrier. The monomers may be polymerized to form a film of the polymers on the solid surface simultaneously with the polymerization.
【００２２】また、吸着補助物質による吸着担体の処理
は、吸着担体を本発明の血液処理装置に組み込む前に行
うのがよい。本発明の吸着担体として好適に使用できる
炭素材料からなる吸着担体は、焼結等の製造条件の微細
な制御が困難であることにより、均一なロットを作りに
くいが、本発明では炭素材料からなる吸着担体の表面に
吸着補助物質を付与することによって、炭素材料からな
る吸着担体の物性を均一に制御することができる。[0022] Furthermore, the treatment of the adsorption carrier with the adsorption auxiliary substance is preferably carried out before the adsorption carrier is incorporated into the blood processing device of the present invention. The adsorption carrier made of a carbon material that can be suitably used as the adsorption carrier of the present invention is difficult to produce in uniform lots because it is difficult to finely control manufacturing conditions such as sintering. By applying an adsorption auxiliary substance to the surface of the adsorption carrier, the physical properties of the adsorption carrier made of carbon material can be uniformly controlled.
【００２３】本発明の血液処理装置および方法の一実施
態様を、血液からのＬＤＬの分離除去を例に挙げて図５
を参照して以下に説明する。図５においては、血液導入
口１２および血液導出口１３を有するカラム１４内に、
硫酸基を有する水不溶性合成樹脂で被覆処理したグラフ
ァイト繊維束からなる吸着担体を作用極１１として、所
定の嵩密度（例えば０．５〜１．５ｇ／ｃｍ３）で充填
する。グラファイト繊維束を、絶縁性接着剤（例えばエ
ポキシ樹脂、ポリウレタン樹脂、低融点ガラス等）で血
液導出口１３側の端部に導線１５ａとの接点を取って接
着する。An embodiment of the blood processing apparatus and method of the present invention is shown in FIG. 5, taking the separation and removal of LDL from blood as an example.
This will be explained below with reference to . In FIG. 5, in a column 14 having a blood inlet 12 and a blood outlet 13,
An adsorption carrier made of a graphite fiber bundle coated with a water-insoluble synthetic resin having a sulfate group is used as the working electrode 11 and is packed at a predetermined bulk density (for example, 0.5 to 1.5 g/cm<3>). The graphite fiber bundle is bonded to the end on the blood outlet 13 side with an insulating adhesive (for example, epoxy resin, polyurethane resin, low melting point glass, etc.), making contact with the conducting wire 15a.
【００２４】一方、飽和カロメル電極からなる参照極１
７と白金線からなる対極１８を、寒天ゲルを充填した塩
橋１９ａ、１９ｂで作用極１１を充填したカラム１４と
各々接続し且つ飽和食塩水からなる電解質２０を満たし
た別々の浴槽２１ａ、２１ｂ中に固定する。各電極１１
、１７、１８からの導線１５ａ、１５ｂ、１５ｃはポテ
ンシオスタット２２に接続されており、このポテンシオ
スタット２２によってグラファイト繊維束からなる作用
極１１の電極電位を規制する。On the other hand, reference electrode 1 consisting of a saturated calomel electrode
7 and a counter electrode 18 made of a platinum wire are connected to the column 14 filled with the working electrode 11 by salt bridges 19a and 19b filled with agar gel, respectively, and separate baths 21a and 21b filled with an electrolyte 20 made of saturated saline solution. Fix it inside. Each electrode 11
, 17, 18 are connected to a potentiostat 22, which regulates the electrode potential of the working electrode 11 made of a graphite fiber bundle.
【００２５】上記のような構成を有する血液処理装置は
、血液中に含まれるＬＤＬなどに代表される静電的に異
方性の高い分子構造を有する不用物の選択的な吸着除去
に好適に使用することができる。例えば、ＬＤＬ除去を
目的とした血液浄化処理においては、例えば図６に示す
血液回路中に図５に示した血液処理装置を組み入れて、
高コレステロール血症患者に対して体外循環処理を行う
とよい。[0025] The blood processing device having the above configuration is suitable for selectively adsorbing and removing waste materials having a highly electrostatically anisotropic molecular structure, such as LDL contained in blood. can be used. For example, in blood purification treatment aimed at removing LDL, the blood processing device shown in FIG. 5 is incorporated into the blood circuit shown in FIG.
Extracorporeal circulation treatment is recommended for patients with hypercholesterolemia.
【００２６】すなわち、患者からの血液は、血液供給口
２３から回路内に導入されて、血液ポンプ２４、チャン
バー２５ａを経て一定流速で血液処理装置（血液浄化器
）１０に供給される。なお、チャンバー２５ａには圧力
ゲージ２６ａを設けてあり、血液浄化器１０の流通抵抗
をモニタリングできるようになっている。血液導入口１
２から導入された血液は、血液浄化器１０内において、
一定電位（例えば−２．０〜＋２．０Ｖ）（塗布する重
合体により応答電位領域が変化する）において分極され
た作用極１１としてのグラファイト繊維束と接触してＬ
ＤＬを吸着処理された後、血液導出口１３から導出され
る。導出された血液は、チャンバー２５ｂおよび圧力ゲ
ージ２６ｂからなるモニタリング部、恒温槽２７および
気泡検知器２８を通って血液供出口２９から再び患者の
体内に戻される。That is, blood from a patient is introduced into the circuit from the blood supply port 23, and is supplied to the blood processing device (blood purifier) 10 at a constant flow rate via the blood pump 24 and chamber 25a. Note that a pressure gauge 26a is provided in the chamber 25a, so that the flow resistance of the blood purifier 10 can be monitored. Blood inlet 1
In the blood purifier 10, the blood introduced from 2 is
The L
After the DL has been adsorbed, it is drawn out from the blood outlet 13. The drawn blood passes through a monitoring section consisting of a chamber 25b and a pressure gauge 26b, a constant temperature bath 27, and a bubble detector 28, and is returned to the patient's body through a blood supply port 29.
【００２７】上記では、血液浄化器１０に直接、全血を
流した場合について説明したが、勿論患者からの血液を
遠心分離等によって一旦血球成分と血漿成分とに分離し
、血漿成分のみを血液浄化器１０に供給して、浄化され
た血漿を得、これを前記の血球成分と再度一緒にして患
者に返送するようにしてもよい。なお、本発明の血液処
理装置は、使用前に精製水、生理的食塩水等を装置内に
充填し、加熱することによって湿熱滅菌処理を施すとよ
い。[0027] In the above, a case has been described in which whole blood is directly poured into the blood purifier 10, but of course, blood from a patient is first separated into blood cell components and plasma components by centrifugation or the like, and only the plasma component is removed from the blood. The purifier 10 may be supplied to obtain purified plasma, which may be recombined with the blood cell components and returned to the patient. The blood processing device of the present invention is preferably subjected to moist heat sterilization by filling purified water, physiological saline, etc. into the device and heating it before use.
【００２８】そして、本発明の血液処理装置は、血液や
血漿からのＬＤＬの吸着、分離だけでなく、静電的に異
方性を有する血液中の他の成分、例えば各種血漿蛋白質
等の高分子物質、胆汁酸、びりるびん、イオン性の低分
子物質、そのような分子で構成された膜を有する血液細
胞等の分離除去または分離回収に使用することができ、
いずれも本発明の範囲に包含される。The blood processing device of the present invention not only adsorbs and separates LDL from blood and plasma, but also adsorbs and separates other electrostatically anisotropic components in blood, such as various plasma proteins. It can be used for the separation and recovery of molecular substances, bile acids, bilirubins, ionic low-molecular substances, blood cells with membranes composed of such molecules, etc.
All are included within the scope of the present invention.
【００２９】[0029]
実施例 １
硫酸基を有するビニル系重合体であるポリ（２−アクリ
ルアミド−２−メチル−１−プロパン硫酸（ＰＡＰＳ；
Ａｌｄｒｉｃｈ Ｃｈｅｍｉｃａｌ Ｃｏ．，Ｉｎｃ．
）の０．０５重量％水溶液にグラファイト繊維束［商品
名ベスファイト：単繊維直径７μｍ；東邦レーヨン（株
）社製］を１時間浸漬した後、遠心分離処理して過剰の
水溶液を除き、１００℃で１時間熱乾燥した。このグラ
ファイト繊維束を蒸留水中に３０分間浸した後、流水で
再度洗浄して熱乾燥した。
上記で重合体で処理したグラファイト繊維束を、ポリカ
ーボネートパイプ（内径１０ｍｍ）に約１．２ｇ／ｃｍ
３の嵩密度になるように充填し、グラファイト繊維束の
片端を導線と接続してエポキシ樹脂で固めて吸着担体内
蔵カラムを形成した（カラム容量３．８ｃｍ３）。この
カラムに塩橋（２％寒天ゲル）を通じて、基準電極であ
る飽和カロメル電極（Ｓ．Ｃ．Ｅ）と対極である白金電
極を接続して、図５に示した血液処理装置（電解電池）
とした。電極間電位はポテンシオスタット［東邦技研（
株）社製；製品番号２００］。Example 1 Poly(2-acrylamide-2-methyl-1-propane sulfate (PAPS); a vinyl polymer having sulfate groups;
Aldrich Chemical Co. , Inc.
) A graphite fiber bundle [trade name Besphite: single fiber diameter 7 μm; manufactured by Toho Rayon Co., Ltd.] was immersed for 1 hour in a 0.05% aqueous solution of It was heat dried at ℃ for 1 hour. This graphite fiber bundle was immersed in distilled water for 30 minutes, washed again with running water, and then heat-dried. The graphite fiber bundle treated with the polymer above was placed in a polycarbonate pipe (inner diameter 10 mm) at a density of approximately 1.2 g/cm.
3, one end of the graphite fiber bundle was connected to a conductive wire and solidified with epoxy resin to form a column with a built-in adsorption carrier (column capacity: 3.8 cm3). A saturated calomel electrode (S.C.E.) as a reference electrode and a platinum electrode as a counter electrode were connected to this column through a salt bridge (2% agar gel) to form the blood processing device (electrolytic battery) shown in Figure 5.
And so. The potential between the electrodes was measured using a potentiostat [Toho Giken (
Co., Ltd.; product number 200].
【００３０】上記で用意した電解電池のカラム内のグラ
ファイト繊維束に所定の電位を設定して、高コレステロ
ール食を３カ月間投与したウサギから採取した高コレス
テロール血漿１０ｍｌを１ｍｌ／分の流速でカラム内を
循環させた。また、上記ビニル系重合体ＰＡＰＳで浸漬
処理しないグラファイト繊維束をカラムに充填し電解電
池を使用して、上記と同様の血漿浄化処理を行った。A predetermined potential was set on the graphite fiber bundle in the column of the electrolytic cell prepared above, and 10 ml of high-cholesterol plasma collected from a rabbit that had been fed a high-cholesterol diet for 3 months was poured into the column at a flow rate of 1 ml/min. circulated inside. In addition, plasma purification treatment similar to that described above was carried out by filling a column with graphite fiber bundles that had not been soaked in the vinyl polymer PAPS and using an electrolytic battery.
【００３１】ここで、電位の設定とビニル系重合体ＰＡ
ＰＳによる浸漬処理の有無による浄化効果の比較を次の
ようにして行った。まず、ビニル系重合体ＰＡＰＳで処
理したグラファイト繊維束で最も高いＬＤＬ除去率を示
した電位を未処理繊維束に設定して、ＬＤＬ除去能を調
べた。また、電位を設定しないビニル系重合体ＰＡＰＳ
処理繊維束と未処理繊維束のＬＤＬ除去能も測定した。
上記における設定電位は−０．５Ｖ ｖｓＳ．Ｃ．Ｅ．
であった。そして、電位を設定したビニル系重合体ＰＡ
ＰＳ処理繊維束のＬＤＬ除去量をＣＦ、未処理繊維束の
ＬＤＬ除去量をＮＦ、電位を設定しない時のビニル系重
合体ＰＡＰＳ処理繊維束のＬＤＬ除去量をＣＦ０、未処
理繊維束のＬＤＬ除去量をＮＦ０として、下記の式によ
り、電位によるＬＤＬ除去効果のビニル系重合体ＰＡＰ
Ｓ中の酸性基による効率化の指標ＥＲＰ（ＰＡＰＳ）と
した。
ＥＲＰ（ＰＡＰＳ） ＝ （ＣＦ／Ｃ
Ｆ０）÷（ＮＦ／ＮＦ０）Here, the potential setting and the vinyl polymer PA
A comparison of the purification effects with and without PS immersion treatment was conducted as follows. First, the potential that showed the highest LDL removal rate in the graphite fiber bundle treated with the vinyl polymer PAPS was set for the untreated fiber bundle, and the LDL removal ability was investigated. In addition, vinyl polymer PAPS that does not set the potential
The LDL removal ability of treated and untreated fiber bundles was also measured. The set potential in the above is -0.5V vsS. C. E.
Met. Then, the vinyl polymer PA with the potential set
The amount of LDL removed from the PS treated fiber bundle is CF, the amount of LDL removed from the untreated fiber bundle is NF, the amount of LDL removed from the vinyl polymer PAPS treated fiber bundle when no potential is set is CF0, and the amount of LDL removed from the untreated fiber bundle is CF0. Assuming the amount of NF0, the vinyl polymer PAP of the LDL removal effect depending on the electric potential is determined by the following formula.
ERP (PAPS) was used as an index of efficiency due to the acidic group in S. ERP(PAPS) = (CF/C
F0) ÷ (NF/NF0)
【００３２】上記式において、ＣＦ／ＣＦ０およびＮＦ
／ＮＦ０は各々電位の有無（グラファイト繊維束の分極
の有無）によるＬＤＬ吸着能の変化を表し、それら各々
の値が１．００を超えた場合は、吸着担体であるグラフ
ァイト繊維束に電位をかけて分極させることによって、
そのＬＤＬの吸着除去能が増大したことを意味する。ま
た、ＥＲＰ（ＰＡＰＳ）は、グラファイト繊維束にビニ
ル系重合体ＰＡＰＳ処理を施した場合と未処理の場合と
のＬＤＬ吸着除去能の比較を表し、ＥＲＰ（ＰＡＰＳ）
の値が１．００を超えた場合は、ビニル系重合体ＰＡＰ
Ｓによる処理によって、吸着担体であるグラファイト繊
維束の電位によるＬＤＬの吸着除去能が強調されたこと
を意味する。循環処理後に回収された血漿中のＬＤＬ含
量、ＮＦ、ＮＦ０、ＣＦ、ＣＦ０の値は、β−Ｌテスト
試薬［極東製薬工業（株）社製］を用いたＬＤＬの比濁
法により測定した。得られた結果を下記の表１に示す。In the above formula, CF/CF0 and NF
/NF0 represents the change in LDL adsorption capacity depending on the presence or absence of potential (the presence or absence of polarization of the graphite fiber bundle), and if each of these values exceeds 1.00, an electric potential is applied to the graphite fiber bundle as an adsorption carrier. By polarizing the
This means that the ability to adsorb and remove LDL has increased. In addition, ERP (PAPS) represents a comparison of the LDL adsorption and removal ability between graphite fiber bundles treated with vinyl polymer PAPS and untreated cases, and ERP (PAPS)
If the value exceeds 1.00, vinyl polymer PAP
This means that the treatment with S emphasized the adsorption and removal ability of LDL due to the potential of the graphite fiber bundle, which is an adsorption carrier. The LDL content, NF, NF0, CF, and CF0 values in the plasma collected after the circulation treatment were measured by nephelometry of LDL using β-L test reagent [manufactured by Kyokuto Pharmaceutical Industries, Ltd.]. The results obtained are shown in Table 1 below.
【００３３】実施例 ２
グラファアイト繊維処理用の重合体をポリビニル硫酸（
ＰＶＳ；Ａｌｄｒｉｃｈ Ｃｈｅｍｉｃａｌ Ｃｏ．，
Ｉｎｃ．）に代え、設定電位を−１．０Ｖ ｖｓＳ．Ｃ
．Ｅ．にした他は、実施例１と同様にして血漿からのＬ
ＤＬ吸着除去状態を調べた。
得られた結果を表１に示す。Example 2 Polyvinyl sulfate (
PVS; Aldrich Chemical Co. ，
Inc. ), set the potential to -1.0V vsS. C
．． E. L from plasma was obtained in the same manner as in Example 1, except that
The state of DL adsorption removal was investigated. The results obtained are shown in Table 1.
【００３４】実施例 ３
ジメチルホルムアミドと０．２Ｍ水酸化ナトリウム水溶
液を１：１の容量割合で混合した混合溶媒中に、オキシ
ラン基含有四元ブロック共重合体であるモディパーＨＴ
−２２８［日本油脂（株）社製；ヒドロキシエチルエタ
クリレート：グリシジルメタクリレート：メチルメタク
リレート：アクリル酸の重合仕込み割合が４０：４０：
１７：３モル％であるポリ（ヒドロキシエチルエタクリ
レート／グリシジルメタクリレート）−ポリ（メチルメ
タクリレート／アクリル酸）ブロック共重合体］を２．
５容量％になるように、更にアミノドデカン酸を０．１
Ｍの濃度になるように加え、得られた溶液を室温で４８
時間撹拌した。生成した沈殿を精製溶媒である１Ｍ水酸
化ナトリウム水溶液とジオキサンを用いて数回洗浄した
。この洗浄された不溶物は、アミノドデカン酸を酸性基
として結合した上記四元ブロック共重合体であった。Example 3 Modiper HT, an oxirane group-containing quaternary block copolymer, was added to a mixed solvent of dimethylformamide and 0.2M sodium hydroxide aqueous solution in a volume ratio of 1:1.
-228 [manufactured by NOF Corporation; the polymerization ratio of hydroxyethyl ethacrylate: glycidyl methacrylate: methyl methacrylate: acrylic acid is 40:40:
17:3 mol% poly(hydroxyethyl ethacrylate/glycidyl methacrylate)-poly(methyl methacrylate/acrylic acid) block copolymer].
Add 0.1% of aminododecanoic acid to 5% by volume.
The resulting solution was heated to a concentration of 48 M at room temperature.
Stir for hours. The generated precipitate was washed several times using a 1M aqueous sodium hydroxide solution and dioxane as purification solvents. The washed insoluble matter was the above-mentioned quaternary block copolymer in which aminododecanoic acid was bonded as an acidic group.
【００３５】このアミノドデカン酸結合四元ブロック共
重合体をジオキサンと酢酸を１：１の容量割合で混合し
た混合溶媒中に濃度が０．０５重量％になるように溶解
させて溶液を形成した。この溶液中に実施例１における
のと同じようにして、グラファイト繊維束を浸漬してそ
の繊維表面にアミノドデカン酸結合四元ブロック共重合
体の層を形成させ、設定電位を＋１．０Ｖ ｖｓ Ｓ．
Ｃ．Ｅ．にして、実施例１におけるのと同様にしてウサ
ギから採取した高コレステロール血漿からのＬＤＬの吸
着除去試験を行った。その結果を表１に示す。[0035] This aminododecanoic acid-bonded quaternary block copolymer was dissolved in a mixed solvent of dioxane and acetic acid in a volume ratio of 1:1 to a concentration of 0.05% by weight to form a solution. . In the same manner as in Example 1, a graphite fiber bundle was immersed in this solution to form a layer of the aminododecanoic acid-bonded quaternary block copolymer on the fiber surface, and the set potential was +1.0 V vs. ．．
C. E. A test for adsorption and removal of LDL from high cholesterol plasma collected from rabbits was conducted in the same manner as in Example 1. The results are shown in Table 1.
【００３６】実施例 ４
１０％のアセトンを含むメタノールからなる溶媒中に、
実施例３で使用したのと同じオキシラン基含有四元ブロ
ック共重合体を２．５容量％になるように、更にアミノ
安息香酸を０．１Ｍの濃度になるように加え、得られた
溶液を室温で４８時間撹拌した。生成した沈殿を１．２
Ｎ塩酸と２０％のアセトンを含有するメタノールを用い
て数回洗浄した。この洗浄された不溶物は、アミノ安息
香酸を酸性基として結合した上記四元ブロック共重合体
であった。このアミノ安息香酸結合四元ブロック共重合
体をジオキサンと酢酸を１：１の容量割合で混合した混
合溶媒中に濃度が０．０５重量％になるように溶解させ
て溶液を形成した。この溶液中に実施例１におけるのと
同じようにして、グラファイト繊維束を浸漬して繊維表
面にアミノ安息香酸結合四元ブロック共重合体の層を形
成させ、設定電位を＋０．５Ｖ ｖｓ Ｓ．Ｃ．Ｅにし
た他は実施例１と同様にしてウサギから採取した高コレ
ステロール血漿からのＬＤＬの吸着除去試験を行った。
その結果を表１に示す。Example 4 In a solvent consisting of methanol containing 10% acetone,
The same oxirane group-containing quaternary block copolymer used in Example 3 was added at a concentration of 2.5% by volume, and aminobenzoic acid was added at a concentration of 0.1M, and the resulting solution was Stirred at room temperature for 48 hours. The generated precipitate is 1.2
Washed several times with N-hydrochloric acid and methanol containing 20% acetone. The washed insoluble matter was the above-mentioned quaternary block copolymer in which aminobenzoic acid was bonded as an acidic group. This aminobenzoic acid-bonded quaternary block copolymer was dissolved in a mixed solvent of dioxane and acetic acid in a volume ratio of 1:1 to a concentration of 0.05% by weight to form a solution. A graphite fiber bundle was immersed in this solution in the same manner as in Example 1 to form a layer of aminobenzoic acid-bonded quaternary block copolymer on the fiber surface, and the set potential was set to +0.5V vs. S. C. A test for adsorption and removal of LDL from high cholesterol plasma collected from rabbits was conducted in the same manner as in Example 1, except that E was used. The results are shown in Table 1.
【００３７】比較例 １
グラファイト繊維の表面に施す重合体としてカチオン基
を有する多糖類であるキトサン［旭ガラス（株）社製Ｃ
ＡＲＡＰＡＣＥ ＣＳ−９０］に替え、設定電位を＋０
．５Ｖ ｖｓ Ｓ．Ｃ．Ｅにした他は実施例１と同様に
してＬＤＬの吸着除去試験を行った。その結果を表１に
示す。
比較例 ２
グラファイト繊維の表面に施す重合体として解離性基を
持たないポリスルホン（アモコ社製のコーデルＰ−１７
００）に替え、設定電位を＋０．５Ｖ ｖｓ Ｓ．Ｃ．
Ｅにした他は、実施例１と同様にしてＬＤＬの吸着除去
試験を行った。その結果を表１に示す。Comparative Example 1 Chitosan, which is a polysaccharide having a cationic group, was used as a polymer applied to the surface of graphite fiber [C manufactured by Asahi Glass Co., Ltd.
ARAPACE CS-90] and set the potential to +0.
．． 5V vs S. C. An LDL adsorption removal test was conducted in the same manner as in Example 1 except that E was used. The results are shown in Table 1. Comparative Example 2 Polysulfone without dissociative groups (Cordel P-17 manufactured by Amoco) was used as a polymer applied to the surface of graphite fibers.
00) and set the set potential to +0.5V vs S. C.
An LDL adsorption removal test was conducted in the same manner as in Example 1, except that E was used. The results are shown in Table 1.
【００３８】[0038]
【表１】[Table 1]
【００３９】実施例 ５
実施例１におけるのと同じビニル系重合体ＰＡＰＳを使
用して、グラファイト繊維束を処理し、設定電位を−０
．５Ｖ ｖｓ Ｓ．Ｃ．Ｅにして実施例１と同じ手順で
高コレステロールウサギ血漿の循環実験を行って、１時
間後の血漿中からのＬＤＬ、ＨＤＬ、アルブミン、総蛋
白質の吸着量を測定した。ＨＤＬ、アルブミンおよび総
蛋白質の測定には、ＨＬＤ−Ｃ・２「第一」（第一化学
薬品社製）およびＡ／ＧＢ−テストワコー（和光純薬社
製）を使用した。その結果を表２に示す。Example 5 The same vinyl polymer PAPS as in Example 1 was used to treat graphite fiber bundles and set the potential to -0.
．． 5V vs S. C. A circulation experiment of high-cholesterol rabbit plasma was conducted using the same procedure as in Example 1, and the amounts of LDL, HDL, albumin, and total protein adsorbed from the plasma after 1 hour were measured. HDL, albumin, and total protein were measured using HLD-C-2 "Daiichi" (manufactured by Daiichi Chemical Co., Ltd.) and A/GB-Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.). The results are shown in Table 2.
【００４０】実施例 ６
グラファイト繊維表面に施す重合体として実施例３で使
用したのと同じアミノドデカン酸結合四元共重合体を使
用した以外は、実施例５と同様にして実験を行った。そ
の結果を表２に示す。
実施例 ７
グラファイト繊維表面に施す重合体として実施例４で使
用したのと同じアミノ安息香酸結合四元共重合体を使用
した以外は、実施例５と同様にして実験を行った。その
結果を表２に示す。Example 6 An experiment was conducted in the same manner as in Example 5, except that the same aminododecanoic acid-bonded quaternary copolymer used in Example 3 was used as the polymer applied to the surface of the graphite fiber. The results are shown in Table 2. Example 7 An experiment was conducted in the same manner as in Example 5, except that the same aminobenzoic acid-bonded quaternary copolymer used in Example 4 was used as the polymer applied to the surface of the graphite fiber. The results are shown in Table 2.
【００４１】[0041]
【表２】[Table 2]
【００４２】表１の結果から、分極された固体表面の静
電的効果を強調する酸性基を有する重合体を塗布した吸
着担体（グラファイト繊維）を備えた本発明の血液処理
装置では、ＬＤＬを効率よく選択的に吸着除去できるの
に対して、重合体で表面処理する場合でも、当該重合体
がカチオン基を有するものや非解離性のものである場合
は、静電的なＬＤＬの吸着除去が強調されないことがわ
かる。また表２の結果から、吸着担体（グラファイト繊
維）を備えた本発明の血液処理装置では、ＬＤＬのみを
効率よく選択的に吸着除去でき、ＨＬＤ、アルブミン、
蛋白質等の有用成分は吸着せずそのまま血漿中に残留さ
せえることがわかる。From the results in Table 1, it is clear that the blood processing device of the present invention, which is equipped with an adsorption carrier (graphite fiber) coated with a polymer having acidic groups that emphasizes the electrostatic effect of the polarized solid surface, can reduce LDL. While LDL can be efficiently and selectively adsorbed and removed, even if the surface is treated with a polymer, if the polymer has a cationic group or is non-dissociable, LDL can be adsorbed and removed electrostatically. It can be seen that is not emphasized. Furthermore, from the results in Table 2, the blood processing device of the present invention equipped with an adsorption carrier (graphite fiber) can efficiently and selectively adsorb and remove only LDL, HLD, albumin,
It can be seen that useful components such as proteins can remain in the plasma as they are without being adsorbed.
【００４３】[0043]
【発明の効果】血液中の特定成分を選択的に吸着除去し
える吸着担体を備え、吸着担体は、電気的に分極された
固体表面を有し、当該固体表面に吸着補助物質が付与さ
れてなる本発明の血液処理による場合は、血液中の分離
しようとする成分の吸着能が一層向上して、より高精度
で選択的に当該特定成分を分離できる。特に、本発明の
処理装置は、虚血性心疾患や各種血管障害、更には単状
糸球体硬化症由来の薬物抵抗性ネフローゼを引き起こす
病因物質とされているコレステロールを多量に含むＬＤ
Ｌを血液、血漿から選択的に分離するのに有用である。
すなわち、本発明の処理装置による場合は、極めて簡単
な操作で、血液中の有用成分であるＨＬＤ、アルブミン
、蛋白質等を血液中にそのまま残留保持させたまま、Ｌ
ＤＬのみを選択的に分離除去できる。本発明の処理装置
では、吸着担体の電気的分極状態および吸着担体の表面
に施す静電気吸引性物質の種類や特性を変化、選択する
ことによって、上記したＬＤＬのみならず、他の成分も
血液中から吸着分離することができる。Effects of the Invention: An adsorption carrier capable of selectively adsorbing and removing specific components in blood is provided, the adsorption carrier has an electrically polarized solid surface, and an adsorption auxiliary substance is applied to the solid surface. According to the blood treatment of the present invention, the adsorption ability of the component to be separated in the blood is further improved, and the specific component can be selectively separated with higher precision. In particular, the processing device of the present invention can treat LD containing a large amount of cholesterol, which is said to be a causative substance that causes ischemic heart disease, various vascular disorders, and even drug-resistant nephrosis derived from uniform glomerulosclerosis.
It is useful for selectively separating L from blood and plasma. That is, in the case of the processing apparatus of the present invention, LLD can be processed with extremely simple operations while leaving HLD, albumin, protein, etc., which are useful components in the blood, remaining in the blood.
Only DL can be selectively separated and removed. In the treatment device of the present invention, by changing and selecting the electrical polarization state of the adsorption carrier and the type and characteristics of the electrostatic attracting substance applied to the surface of the adsorption carrier, not only the above-mentioned LDL but also other components can be absorbed into the blood. can be adsorbed and separated from
【図１】本発明の血液処理装置に適用可能な分極状態を
得るための電圧の印加原理の一例を示す図である。FIG. 1 is a diagram showing an example of the principle of voltage application to obtain a polarized state applicable to the blood processing apparatus of the present invention.
【図２】本発明の血液処理装置に適用可能な分極状態を
得るための電圧の印加原理の別の例を示す図である。FIG. 2 is a diagram showing another example of the principle of voltage application to obtain a polarized state applicable to the blood processing apparatus of the present invention.
【図３】本発明の血液処理装置に適用可能な分極状態を
得るための電圧の印加原理の更に別の例を示す図である
。FIG. 3 is a diagram showing still another example of the principle of voltage application to obtain a polarized state applicable to the blood processing apparatus of the present invention.
【図４】本発明の血液処理装置に適用可能な分極状態を
得るための電圧の印加原理の更に別の例を示す図である
。FIG. 4 is a diagram showing still another example of the principle of voltage application to obtain a polarized state applicable to the blood processing apparatus of the present invention.
【図５】本発明の血液処理装置の一実施態様を示す図で
ある。FIG. 5 is a diagram showing an embodiment of the blood processing device of the present invention.
【図６】本発明の血液処理装置を組み込んだ血液の体外
循環回路を示す図である。FIG. 6 is a diagram showing an extracorporeal blood circulation circuit incorporating the blood processing device of the present invention.
１ 電解質 ２ 電極 ３ 電極 ４ 絶縁体 ５ 基準電極 ６ 作用極 ７ 対極 １０ 血液処理器 １１ 作用極 １２ 血液導入口 １３ 血液導出口 １４ カラム １５ａ 導線 １７ 参照極 １９ａ 塩橋 ２２ ポテンシオスタット ２３ 血液供給口 ２９ 血液供出口 1. Electrolyte 2 Electrode 3 Electrode 4 Insulator 5 Reference electrode 6 Working electrode 7. Opposite 10 Blood processing device 11 Working electrode 12 Blood introduction port 13 Blood outlet 14 Column 15a Conductor 17 Reference pole 19a Shiobashi 22 Potentiostat 23 Blood supply port 29 Blood donation outlet
Claims (5)
る吸着担体を備えた血液処理装置であって、前記吸着担
体は、電気的に分極された固体表面を有し、かつ当該固
体表面には吸引補助物質が付与されてなることを特徴と
する血液処理装置。1. A blood processing device equipped with an adsorption carrier capable of selectively adsorbing specific components in blood, wherein the adsorption carrier has an electrically polarized solid surface, and the solid surface has an electrically polarized solid surface. A blood processing device characterized in that a suction auxiliary substance is added to the blood processing device.
記特定成分が低密度リポ蛋白質である請求項１記載の血
液処理装置。2. The blood processing device according to claim 1, wherein the blood processing device is a blood purifier, and the specific component is low density lipoprotein.
高分子物質である請求項１または２記載の血液処理装置
。3. The blood processing device according to claim 1, wherein the suction auxiliary substance is a polymer substance having a dissociable group.
および／またはカルボン酸基を有する高分子物質である
請求項３記載の血液処理装置。4. The blood processing device according to claim 3, wherein the polymeric substance having a dissociative group is a polymeric substance having a sulfuric acid group and/or a carboxylic acid group.
極された固体表面を有し且つ当該固体表面には吸着補助
物質が付与されてなる吸着担体に接触させ、静電的相互
作用により血液中に含まれる静電的に異方性の高い分子
構造を有する不用物を選択的に吸着することを特徴とす
る血漿処理方法。5. Blood to be treated is brought into contact with an adsorption carrier having an electrically polarized solid surface and an adsorption auxiliary substance is applied to the solid surface, and the blood is absorbed by electrostatic interaction. 1. A plasma processing method characterized by selectively adsorbing waste substances contained in plasma having a highly electrostatically anisotropic molecular structure.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3067544A JPH04314456A (en) | 1991-03-08 | 1991-03-08 | Blood treating apparatus and method for treating plasma |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3067544A JPH04314456A (en) | 1991-03-08 | 1991-03-08 | Blood treating apparatus and method for treating plasma |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04314456A true JPH04314456A (en) | 1992-11-05 |
Family
ID=13348015
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3067544A Pending JPH04314456A (en) | 1991-03-08 | 1991-03-08 | Blood treating apparatus and method for treating plasma |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04314456A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019519290A (en) * | 2016-05-26 | 2019-07-11 | ドレクセル ユニバーシティ | Open-curved graphite material for adsorbing cytokines from blood |
-
1991
- 1991-03-08 JP JP3067544A patent/JPH04314456A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019519290A (en) * | 2016-05-26 | 2019-07-11 | ドレクセル ユニバーシティ | Open-curved graphite material for adsorbing cytokines from blood |
| US11918723B2 (en) | 2016-05-26 | 2024-03-05 | Drexel University | Methods of using graphine nanoplatelets or polymer-derived ceramic carbide-derived carbon to remove proteins from blood and to treat sepsis |
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