JPH0611332B2 - Adsorbent and adsorption method - Google Patents
Adsorbent and adsorption methodInfo
- Publication number
- JPH0611332B2 JPH0611332B2 JP61268054A JP26805486A JPH0611332B2 JP H0611332 B2 JPH0611332 B2 JP H0611332B2 JP 61268054 A JP61268054 A JP 61268054A JP 26805486 A JP26805486 A JP 26805486A JP H0611332 B2 JPH0611332 B2 JP H0611332B2
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- Prior art keywords
- adsorbent
- amyloid precursor
- porous body
- pore volume
- precursor protein
- Prior art date
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- Treatment Of Liquids With Adsorbents In General (AREA)
Description
【発明の詳細な説明】 ［産業上の利用分野］ 本発明は体液から有害な成分を取り除くための吸着体に
関する。さらに詳しくは体液に含有されるアミロイド前
駆物質を選択的に吸着除去するための吸着体に関する。TECHNICAL FIELD The present invention relates to an adsorbent for removing harmful components from body fluids. More specifically, it relates to an adsorbent for selectively adsorbing and removing an amyloid precursor contained in a body fluid.
［従来の技術および発明が解決しようとする問題点］ アミロイド−シスはアミロイド物質と呼ばれるβ−フィ
ブリル状の蛋白が血管、組織、臓器に沈着し心、腎など
の臓器不全、心刺激伝導障害、進行性痴呆、脳血管障
害、神経障害などの重篶な障害を引き起こす疾患であ
り、確立された治療法は現在のところまったくない。[Problems to be Solved by Conventional Techniques and Inventions] Amyloidosis is a β-fibrillar protein called amyloid substance deposited in blood vessels, tissues and organs, resulting in organ failure such as heart and kidney, impaired cardiac stimulation conduction, It is a disease that causes serious disorders such as progressive dementia, cerebrovascular disorder, and neuropathy, and there is currently no established treatment method.
アミロイド−シスには原発性、続発性、家族性、老人性
などの病型が存在することが知られているが、いずれの
病型においても沈着したアミロイド物質はコンゴーレッ
ド染色により緑色偏光を生じ、その構造はβ−シート構
造である。It is known that there are primary, secondary, familial, senile, and other types of amyloidosis, but in any of the types, the deposited amyloid substance produces green polarized light due to Congo red staining. , Its structure is a β-sheet structure.
長期にわたって人工透析を受けた患者に手根管症侯群と
呼ばれる疾患が近年多発しているが、このばあいも患部
に前記の特徴を有するアミロイド物質が沈着しているこ
とが最近明らかとなった。In recent years, a disease called carpal tunnel syndrome has frequently occurred in patients who have undergone artificial dialysis for a long period of time, but in this case as well, it has recently become clear that an amyloid substance having the above characteristics is deposited in the affected area. It was
しかしながらその蛋白組成は病型により異なり、原発性
はAL、連続性はAA、老人性はASと呼ばれる蛋白によりそ
れぞれ形成されている。また長期透析によるアミロイド
−シスではβ２−ミクログロブリン類似蛋白が、家族性
については家系により異なるがプレアルブミン類似蛋白
などが沈着する。However, its protein composition differs depending on the type of disease. Primary protein is AL, continuous protein is AA, and senile protein is formed by AS. The amyloid long-term dialysis - the cis beta 2 - is microglobulin similar proteins, for familial varies depending families will be deposited, such as prealbumin similar protein.
それぞれの病型において沈着するアミロイド−シス物質
に対応する前駆物質が患者血液中に存在することが明ら
かになりつつある。原発性においてはイムノグロブリン
のライトチェイン(SAL)、続発性においてはアポリボ蛋
白の１種であるSAA蛋白、長期透析性ではβ２−ミクロ
グロブリン、プレアルブミン類似蛋白が沈着する家族性
アミロイド−シスでは異常プレアルブミンがそれぞれ前
駆物質であるとされている。It is becoming clear that there are precursors in the patient's blood corresponding to the deposited amyloid-cis substances in each type of disease. In primary, immunoglobulin light chain (SAL), in secondary, SAA protein, which is one of apoliboproteins, in long-term dialysis, β 2 -microglobulin, and in predominant amyloidosis with prealbumin-like protein deposition Abnormal prealbumin is said to be the precursor, respectively.
アミロイド−シスは前記のごとく重篶な疾患であり、死
亡率も高いことからその治療法について盛んに研究され
てきたが、これまでのところ有効な治療法、とくに薬物
療法は見出されていない。Amyloidosis is a serious disease as described above, and its mortality rate is high, and therefore, its therapeutic method has been extensively studied, but so far, no effective therapeutic method, particularly drug therapy has been found. .
一方近年盛んに行われるようになってきた体外循環によ
る血液浄化法、とりわけプラズマフエレーシスによりア
ミロイド−シスを治療する試みがなされており、前記の
前駆物質を多量に含有する患者血漿を正常血漿と交換す
ることにより症状の軽快、病変の進行停止が見られると
の報告がなされている。On the other hand, attempts have been made to treat amyloidosis by plasma purification by extracorporeal circulation, which has been actively performed in recent years, and especially by plasmapheresis, and patient plasma containing a large amount of the above-mentioned precursors is treated with normal plasma. It has been reported that the symptoms may be alleviated and the progression of the lesion may be stopped by exchanging with.
体外循環による血液浄化法とりわけ血漿交換法は現在の
ところ最も有効な治療であるが、高価かつ貴重な正常血
漿あるいは血漿製剤を大量に使用すること、また患者血
漿中に含まれる前駆物質以外の有用成分も同時に廃棄さ
れるなどの欠点を有しているため、前駆物質をより選択
的に除去する方法の開発が強く望まれている。Blood purification by extracorporeal circulation, especially plasmapheresis, is currently the most effective treatment, but it requires the use of large amounts of expensive and valuable normal plasma or plasma preparations, and is useful for other than precursors contained in patient plasma. Since the components also have the drawback of being discarded at the same time, the development of a method for more selectively removing the precursor is strongly desired.
血漿中の成分をそのサイズによりある程度選択的に分離
する方法として限外濾過膜による分離法が知られている
が、上記のアミロイド前駆物質は血漿中の有用成分であ
るアルブミン、ガンマグロブリンなどの蛋白とサイズが
近いため前駆物質を同法により分離廃棄しようとすると
同時にこれらの有用蛋白も失われることから同法はアミ
ロイド前駆物質の除去には適していない。An ultrafiltration membrane separation method is known as a method for selectively separating plasma components depending on their size. The amyloid precursors described above are useful components of plasma such as albumin and gamma globulin. This method is not suitable for the removal of amyloid precursors because the useful substances are lost at the same time when the precursors are separated and discarded by the same method due to their close size.
したがって膜分離以外の選択的除去方法が望まれている
が、現在のところ実用的なアミロイド前駆物質の除去方
法は開発されていない。Therefore, a selective removal method other than membrane separation is desired, but a practical method for removing an amyloid precursor has not been developed so far.
［問題点を解決するための手段］ ポリスチレンを主構成成分とする多孔体であることを特
徴とするアミロイド前駆蛋白の吸着体に関する。[Means for Solving Problems] The present invention relates to an adsorbent for an amyloid precursor protein, which is a porous body mainly composed of polystyrene.
また、該吸着体を流体の入口と出口を有する容器に充填
した後、アミロイド前駆蛋白を含む体液を流通させるこ
とを特徴とする体液からアミロイド前駆蛋白を除去する
方法に関する。The present invention also relates to a method for removing amyloid precursor protein from a body fluid, which comprises filling the container having the inlet and outlet of a fluid with the adsorbent and then circulating a body fluid containing the amyloid precursor protein.
［実施例］ 本明細書でいう体液とは血液、血漿、血清、腹水、リン
パ液、関節内液およびこれらから得られた分画成分その
他の生体由来の液性成分を含有するものを指す。[Examples] The body fluid referred to in the present specification refers to one containing blood, plasma, serum, ascites fluid, lymph fluid, synovial fluid, and fractionated components obtained from these and other biologically derived liquid components.
本発明の吸着体は体液よりアミロイド前駆蛋白を選択的
かつ効率よく除去するのに適した吸着体であり、とりわ
け体外循環によりアミロイド前駆蛋白を除去する方法に
適している。The adsorbent of the present invention is an adsorbent suitable for selectively and efficiently removing amyloid precursor protein from body fluid, and is particularly suitable for a method of removing amyloid precursor protein by extracorporeal circulation.
体外循環用の吸着体には一般の吸着体に比べ様々の性質
が要求される。An adsorbent for extracorporeal circulation is required to have various properties as compared with a general adsorbent.
要求される性質とはすなわち、 (1)ある程度の高速で体液を処理する必要があるため、
カラム等に充填して体液を流通させたばあいの圧力喪失
が小さく、吸着体粒子の変形による目詰り圧密化をおこ
さないこと、 (2)機械的強度が高く振動衝撃により破砕せず、微粉を
生じないこと、 (3)高圧蒸気滅菌、放射線滅菌、薬剤による滅菌などの
滅菌操作により化学的あるいは物理的な変化を受けにく
いこと、そして、 (4)毒性が低いこと などである。The required properties are: (1) Since it is necessary to process body fluid at a high speed to some extent,
There is little pressure loss when filling the column etc. and circulating the bodily fluid, and it does not cause clogging and consolidation due to deformation of the adsorbent particles. (2) High mechanical strength does not crush due to vibration impact, and produces fine powder. It does not occur, (3) is less susceptible to chemical or physical changes due to sterilization operations such as high-pressure steam sterilization, radiation sterilization, sterilization with chemicals, and (4) has low toxicity.
本発明者らは前記の条件を満たし体液よりアミロイド前
駆蛋白を選択的かつ効率的に除去しうる吸着体につき鋭
意研究の結果、ポリスチレンを主構成成分とする多孔体
が優れていることを見出し本発明に至った。As a result of earnest research on an adsorbent capable of selectively and efficiently removing amyloid precursor protein from a body fluid satisfying the above conditions, the present inventors have found that a porous body containing polystyrene as a main constituent is superior. Invented.
ポリスチレンを主構成成分とする多孔体が選択的かつ効
率的にアミロイド前駆蛋白を吸着する理由は必ずしも明
らかではないが、ポリスチレン鎖がアミロイド前駆蛋白
の疎水性部位と適度なインターラクシヨンを有するため
と考えられる。The reason why the porous body mainly composed of polystyrene adsorbs the amyloid precursor protein selectively and efficiently is not always clear, but because the polystyrene chain has a moderate interaction with the hydrophobic site of the amyloid precursor protein. Conceivable.
本発明に用いるポリスチレンを主構成成分とする多孔体
とは、多孔体を構成する高分子鎖の内、 （式中、Ｒ１は水素原子またはメチル基）で表されるモ
ノマー単位が高分子を構成する全モノマー単位中少なく
とも50モル％以上であるものをいう。前記モノマー単位
中のベンゼン環上の水素原子はその１部が炭素数１から
６のアルキル基、アミノ基、カルボキシル基、スルフォ
ン基、硫酸エステル基またはこれらの官能基を含む置換
基その他で置換されていてもよい。The porous body having a polystyrene as a main constituent component used in the present invention, among the polymer chains constituting the porous body, (In the formula, R 1 is a hydrogen atom or a methyl group) means at least 50 mol% of all the monomer units constituting the polymer. One part of the hydrogen atom on the benzene ring in the monomer unit is substituted with an alkyl group having 1 to 6 carbon atoms, an amino group, a carboxyl group, a sulfone group, a sulfuric acid ester group or a substituent containing these functional groups or the like. May be.
本発明に用いるポリスチレンを主構成成分とする多孔体
はすべてが前記のモノマー単位よりなるものであっても
よいし、50モル％未満の他のモノマー単位を含んでいて
もよい。他のモノマー単位としてはジビニルベンゼン、
ジアリルフタレートなどの二官能ビニルあるいはアリル
化合物、エチレン、プロピレン、酢酸ビニル、ビニルア
ルコール、塩化ビニル、アクリル酸、メタクリル酸、メ
チルアクリレート、メチルメタクリレートなどのビニル
化合物、ブタジエン、イソプレンなどのジエン化合物な
どがあげられるがこれらに限定されるわけではない。The porous body mainly composed of polystyrene used in the present invention may be composed of the above monomer units, or may contain less than 50 mol% of other monomer units. Other monomer units include divinylbenzene,
Examples include bifunctional vinyl or allyl compounds such as diallyl phthalate, ethylene, propylene, vinyl acetate, vinyl alcohol, vinyl chloride, vinyl compounds such as acrylic acid, methacrylic acid, methyl acrylate and methyl methacrylate, and diene compounds such as butadiene and isoprene. However, it is not limited to these.
ポリスチレンを主構成成分とする多孔体は架橋されてい
てもよいし、されていなくともよいが、架橋されている
ばあいは比較的強度が高く、とくに耐熱性薬品性などが
向上するためより好ましい。The porous body having polystyrene as a main constituent may or may not be crosslinked, but when crosslinked, it is relatively high in strength, and particularly preferable because heat resistance and chemical resistance are improved. .
本発明に用いるポリスチレンを主構成成分とする多孔体
は、連続した適度な孔径を多数有するものが好ましい。The porous body mainly composed of polystyrene used in the present invention preferably has a large number of continuous and appropriate pore diameters.
多孔体の細孔径、細孔容積、細孔分布の測定法としては
水銀ポロシメーターによる方法、窒素ガス吸着法（BET
法）が代表的である。これらの方法は多孔体を乾燥状態
で測定するものであり、一般に多孔体の細孔状態は溶液
中とは異なるが、ポリスチレンを主構成成分とする多孔
体においては変化が少なく、これらの測定法による値は
溶液中での細孔状態をよく反映していると考えられる。Methods for measuring the pore size, pore volume, and pore distribution of porous materials are the mercury porosimeter method, nitrogen gas adsorption method (BET
Law) is typical. These methods are for measuring the porous body in a dry state, and generally the pore state of the porous body is different from that in the solution, but there is little change in the porous body having polystyrene as the main constituent, and these measuring methods are used. It is considered that the value obtained by means well reflects the state of pores in the solution.
本発明に用いる多孔体の好ましい細孔容積は0.2ml／ｇ
以上であり、より好ましくは0.5ml／ｇ以上である。細
孔容積が0.2ml／ｇ未満では吸着対象蛋白の吸着に有効
な表面積が小さく十分な吸着量がえられない。The preferred pore volume of the porous material used in the present invention is 0.2 ml / g.
It is above, more preferably 0.5 ml / g or above. If the pore volume is less than 0.2 ml / g, the surface area effective for adsorbing the protein to be adsorbed is small and a sufficient adsorption amount cannot be obtained.
本発明に用いるポリスチレンを主構成成分とする多孔体
の平均細孔径は50Å以上であることが好ましく、100Å
以上であることがより好ましい。平均孔径が50Å未満で
はアミロイド前駆蛋白の細孔内への拡散が遅く十分な吸
着量がえられない。とくに前記蛋白が会合しているばあ
いは蛋白の実質的な分子量が大きくなるためより拡散速
度が小さくなる。The average pore size of the porous body mainly composed of polystyrene used in the present invention is preferably 50 Å or more, 100 Å
The above is more preferable. If the average pore size is less than 50Å, the diffusion of amyloid precursor protein into the pores is slow and sufficient adsorption cannot be obtained. In particular, when the above-mentioned proteins are associated with each other, the substantial molecular weight of the protein becomes large and the diffusion rate becomes smaller.
また平均細孔径が大きすぎても吸着体の表面積が小さく
なり吸着容量が低下し、また吸着対象蛋白以外の吸着、
いわゆる非特異吸着が多くなり、選択性が低下するため
好ましくない。また細孔径が大きすぎると、吸着体が脆
くなり衝撃により破砕され微粉を生じやすくなるため対
外循環治療用吸着体としては好ましくない。好ましい平
均細孔径は1500Å以下である。Also, if the average pore size is too large, the surface area of the adsorbent will be small and the adsorption capacity will be reduced.
The so-called non-specific adsorption increases and the selectivity decreases, which is not preferable. On the other hand, if the pore size is too large, the adsorbent becomes brittle and is easily crushed by impact to generate fine powder, which is not preferable as an adsorbent for external circulation therapy. A preferable average pore diameter is 1500 Å or less.
従って本発明に用いるポリスチレンを主構成成分とする
多孔体の平均細孔径は50以上1500Å以下が好ましい。Therefore, the average pore diameter of the porous body containing polystyrene as the main constituent in the present invention is preferably 50 or more and 1500Å or less.
つぎに本発明に用いるポリスチレンを主構成成分とする
多孔体の細孔分布は狭いほど選択性が向上し好ましい
が、平均細孔径が上記の範囲にあれば必ずしも狭い範囲
に分布している必要はない。好ましい細孔分布の目安と
しては、全細孔容積の内50％以上が50以上1500Å以下の
孔径の細孔により占められていることがあげられる。50
以上1500Å以下の孔径の細孔により占められる細孔容積
が全細孔容積に占める割合が50％未満では、1500Å以上
の細孔が多いばあいは表面積が小さく十分な吸着量がえ
られなかったりあるいは非特異吸着が多いなどの不都合
がある。また小さい孔径の細孔が多いばあいも平均細孔
径が小さいばあいと同様十分な吸着量がえられず好まし
くない。Next, the narrower the pore distribution of the porous body mainly composed of polystyrene used in the present invention is, the more the selectivity is improved. However, if the average pore size is in the above range, it is not always necessary to distribute it in a narrow range. Absent. A preferable index of the pore distribution is that 50% or more of the total pore volume is occupied by pores having a pore size of 50 or more and 1500Å or less. 50
If the ratio of the pore volume occupied by pores with a pore size of 1500 Å or less to the total pore volume is less than 50%, the surface area is small and sufficient adsorption cannot be obtained if there are many pores of 1500 Å or more. Alternatively, there are many inconveniences such as non-specific adsorption. Also, when there are many small pores, it is not preferable because a sufficient amount of adsorption cannot be obtained as when the average pore diameter is small.
また細孔分布が広すぎて平均孔径が決定しにくいばあい
も上記の基準に当てはまる細孔分布であれば本発明に適
している。Further, when the pore distribution is too wide and the average pore diameter is difficult to determine, any pore distribution that meets the above criteria is suitable for the present invention.
本発明に用いるポリスチレンを主構成成分とする多孔体
の表面積は、吸着体の飽和吸着量を決定する重要な要素
であり、少なくとも50m2／ｇ以上が好ましい。The surface area of the porous body mainly composed of polystyrene used in the present invention is an important factor that determines the saturated adsorption amount of the adsorbent, and is preferably at least 50 m 2 / g or more.
次に本発明に用いるポリスチレンを主構成成分とする多
孔体の粒子径は10以上300μｍ以下が好ましい。10μｍ
未満では吸着体の濾別が困難であり、またカラム等に充
填して体液を流通する際の圧力喪失が大きくなり好まし
くない。また3000μｍを越えると吸着対象物であるアミ
ロイド前駆蛋白の粒子内への拡散に時間がかかるため、
吸着速度が低下し好ましくない。より好ましい粒径は40
μｍ以上1500μｍ以下である。Next, the particle diameter of the porous body containing polystyrene as the main constituent in the present invention is preferably 10 or more and 300 μm or less. 10 μm
If it is less than the above range, it is difficult to separate the adsorbent by filtration, and the pressure loss at the time of filling the column or the like and circulating the body fluid becomes large, which is not preferable. If it exceeds 3000 μm, it takes time for the amyloid precursor protein that is an adsorption target to diffuse into the particles.
The adsorption rate is reduced, which is not preferable. More preferable particle size is 40
It is not less than μm and not more than 1500 μm.
本発明による吸着体を用いて体液よりアミロイド前駆蛋
白を吸着除去する方法には種々の方法がある。代表的な
方法としては、体液を取り出してバッグなどに貯留し、
これに吸着体を混合してアミロイド前駆蛋白を吸着除去
したのち、吸着体を濾別してアミロイド前駆蛋白の除去
された体液を得る方法、体液の入り口と出口を有し、出
口に体液は通過するが吸着体は通過しないフィルターを
装着した容器に吸着体を充填し、これに体液を流す方法
などがある。いずれの方法を用いてもよいが後者の方法
は操作も簡単であり、また体外循環回路に組み込むこと
により患者の体液、とくに血液あるいは血漿から効率よ
くオンラインでアミロイド前駆蛋白を除去することが可
能であり、すでに述べたごとく本発明の吸着体はこの方
法にもっとも適している。There are various methods for adsorbing and removing amyloid precursor protein from body fluid using the adsorbent of the present invention. As a typical method, body fluid is taken out and stored in a bag,
A method for obtaining a body fluid from which the amyloid precursor protein has been removed by filtering the adsorbent after adsorbing and removing the amyloid precursor protein by admixing this with the body fluid having an inlet and an outlet for the body fluid There is a method in which a container equipped with a filter that does not pass the adsorbent is filled with the adsorbent, and bodily fluid is allowed to flow into the container. Either method may be used, but the latter method is easy to operate, and by incorporating it into the extracorporeal circulation circuit, it is possible to efficiently and online remove amyloid precursor protein from the body fluid of a patient, especially blood or plasma. And, as already mentioned, the adsorbent of the present invention is most suitable for this method.
以下実施例により本発明をさらに詳しく説明するが、本
発明は以下の実施例のみに限定されるものではない。Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples.
実施例１ スチレン−ジビニルベンゼン共重合体であるダイヤイオ
ンHP10（三菱化成（株）製、比表面積500m2／ｇ細孔容
積0.89ml／ｇ、50以上1500Å以下の細孔容積が全細孔容
積の80％）、ダイヤイオンHP20（三菱化成（株）製、比
表面積720m2／ｇ、細孔容積1.1ml／ｇ、50以上1500Å以
下の細孔容積の70％）、ダイヤイオンHP50（三菱化成
（株）製、比表面積590m2／ｇ、細孔容積0.87ml／ｇ、5
0以上1500Å以下の細孔容積が全細孔容積の60％）、ダ
イヤイオンSP206（三菱化成（株）製、比表面積160m2／
ｇ細孔容積0.4ml／ｇ50以上1500Å以下の細孔容積が全
細孔容積の55％）、いずれも粒径範囲は50から400μ
ｍ、およびアンバーライトXAD-2（ロームアンドハース
社製、比表面積300m2／ｇ、細孔容積0.65ml／ｇ、平均
細孔径90Å）、粒径100から500μｍ、をそれぞれ純水で
よく洗浄したのち、吸着体の10倍量の生理食塩液で洗浄
した。Example 1 Diaion HP10 (manufactured by Mitsubishi Kasei Co., Ltd., which is a styrene-divinylbenzene copolymer, specific surface area 500 m 2 / g, pore volume 0.89 ml / g, pore volume of 50 or more and 1500 Å or less, total pore volume) 80%), Diaion HP20 (manufactured by Mitsubishi Kasei Co., Ltd., specific surface area 720 m 2 / g, pore volume 1.1 ml / g, 70% of pore volume of 50 or more and 1500 Å or less), Diaion HP50 (Mitsubishi Kasei) Co., Ltd., specific surface area 590 m 2 / g, pore volume 0.87 ml / g, 5
Pore volume of 0 or more and 1500Å or less is 60% of the total pore volume), Diaion SP206 (manufactured by Mitsubishi Kasei Co., Ltd., specific surface area 160 m 2 /
g Pore volume 0.4 ml / g Pore volume of 50 or more and 1500Å or less is 55% of the total pore volume), and the particle size range is 50 to 400μ in both cases.
m and Amberlite XAD-2 (manufactured by Rohm and Haas Co., specific surface area 300 m 2 / g, pore volume 0.65 ml / g, average pore size 90 Å), particle size 100 to 500 μm, were thoroughly washed with pure water. Then, the adsorbent was washed with 10 times the physiological saline solution.
つぎに各吸着体１mlづつを試験管に取りこれにβ-2ミク
ログロブリンを多く含む長期透折患者の血清４mlを加
え、振盪しながら37℃で２時間インキュベートした。コ
ントロールとして吸着体のかわりに生理食塩液１mlに同
血清４mlを加えて同様にインキュベートした。Next, 1 ml of each adsorbent was placed in a test tube, and 4 ml of serum of a long-term transfused patient containing a large amount of β-2 microglobulin was added thereto, and the mixture was incubated at 37 ° C for 2 hours while shaking. As a control, 4 ml of the same serum was added to 1 ml of physiological saline instead of the adsorbent and incubated in the same manner.
インキュベート終了後各試験管を遠心器にかけて吸着体
と血清を分離したのち、血清中のβ-2ミクログロリン、
アルブミン、総蛋白濃度およびイムノグロブリンＡ、Ｇ
およびＭを測定した。After completion of the incubation, centrifuge each test tube to separate the adsorbent and serum, then β-2 microglorin in serum,
Albumin, total protein concentration and immunoglobulins A, G
And M were measured.
第１表に結果を示す。The results are shown in Table 1.
実施例２ スチレン−ジビニルベンゼンン共重合体であるダイヤイ
オンHP20、HP50、HP2MG（三菱化成（株）製、比表面積4
60m2／ｇ、細孔容積1.2ml／ｇ、最頻度細孔半径100-100
0Å、50以上1500Å以下の細孔容積が全細孔容積の70
％）を用い、イムノグロブリンライトチェイン（λ型）
を多く含む、多発性骨髄腫にアミロイド−シスを合併し
た患者の血清を用いたほかは、実施例１と同様にして吸
着実験を行った。 Example 2 Styrene-divinylbenzene copolymer DIAION HP20, HP50, HP2MG (Mitsubishi Kasei Co., Ltd., specific surface area 4
60m 2 / g, pore volume 1.2ml / g, most frequent pore radius 100-100
The pore volume of 0Å, 50 or more and 1500Å or less is 70 of the total pore volume.
%), Immunoglobulin light chain (λ type)
An adsorption experiment was performed in the same manner as in Example 1 except that the serum of a patient with multiple myeloma and amyloid-cis, which contained a large amount of the above, was used.
結果を第２表に示す。The results are shown in Table 2.
実施例３ スチレン−ジビニルベンゼン共重合体であるダイヤイオ
ンHP20、HP50、HP2MG、アンバーライトXAD-4を用い、異
常プレアルブミンを含む（全プレアルブミン中約50％）
家族性アミロイド−シス患者の血清を用いた他は実施例
１と同様にして吸着実験を行った。異常プレアルブミン
の吸着率は、ほぼ同濃度のプレアルブミンを含む正常血
清を用いた吸着実験結果との差から求めた。 Example 3 Styrene-divinylbenzene copolymer Diaion HP20, HP50, HP2MG, and Amberlite XAD-4 were used, and abnormal prealbumin was contained (about 50% in total prealbumin).
An adsorption experiment was conducted in the same manner as in Example 1 except that the serum of a familial amyloidosis patient was used. The adsorption rate of abnormal prealbumin was calculated from the difference from the adsorption experiment results using normal serum containing prealbumin at almost the same concentration.
結果を第３表に示す。The results are shown in Table 3.
［発明の効果］ 本発明のアミロイド前駆蛋白の吸着体はアミロイド前駆
蛋白を体液中より他の有効成分を除去することなしに選
択的かつ効率的に除去しうるものである。また、本発明
の吸着方法は操作が簡単であり、また体外循環回路に組
み込むことにより患者の体液、とくに血液あるいは血漿
から効率よくオンラインでアミロイド前駆蛋白を除去す
ることが可能なものである。したがって、本発明は、ア
ミロイド前駆物質を除去することによって、アミロイド
−シスの治療に寄与するものである。 [Advantages of the Invention] The adsorbent for amyloid precursor protein of the present invention can selectively and efficiently remove amyloid precursor protein from body fluids without removing other active ingredients. Further, the adsorption method of the present invention is easy to operate, and when incorporated into an extracorporeal circulation circuit, it is possible to efficiently and online remove amyloid precursor protein from a body fluid of a patient, particularly blood or plasma. Therefore, the present invention contributes to the treatment of amyloid-cis by removing the amyloid precursor.
Claims (5)
あることを特徴とするアミロイド前駆蛋白の吸着体。1. An adsorbent for an amyloid precursor protein, which is a porous body mainly composed of polystyrene.
る多孔体であることを特徴とする特許請求の範囲第１項
記載の吸着体。2. The adsorbent according to claim 1, which is a porous body containing crosslinked polystyrene as a main constituent.
つ比表面積が50m2／ｇ以上であることを特徴とする特許
請求の範囲第１項記載の吸着体。3. The adsorbent according to claim 1, wherein the porous body has a pore volume of 0.2 ml / g or more and a specific surface area of 50 m 2 / g or more.
100以上1500オングストローム以下の細孔によりしめら
れていることを特徴とする特許請求の範囲第１項記載の
吸着体。4. 50% or more of the pore volume of the porous body is the pore size
The adsorbent according to claim 1, wherein the adsorbent has pores of 100 or more and 1500 angstroms or less.
の入り口と出口を有する容器に充填した後、アミロイド
前駆蛋白を含む体液を流通させることを特徴とする体液
からアミロイド前駆蛋白を吸着除去する方法。5. A container having an inlet and an outlet for a fluid is filled with the adsorbent according to claim 1, and then a body fluid containing amyloid precursor protein is circulated, whereby the amyloid precursor protein is obtained from the body fluid. Method of adsorption removal.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61268054A JPH0611332B2 (en) | 1986-11-11 | 1986-11-11 | Adsorbent and adsorption method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61268054A JPH0611332B2 (en) | 1986-11-11 | 1986-11-11 | Adsorbent and adsorption method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63122463A JPS63122463A (en) | 1988-05-26 |
| JPH0611332B2 true JPH0611332B2 (en) | 1994-02-16 |
Family
ID=17453241
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61268054A Expired - Lifetime JPH0611332B2 (en) | 1986-11-11 | 1986-11-11 | Adsorbent and adsorption method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0611332B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020081165A (en) * | 2018-11-20 | 2020-06-04 | 株式会社クレハ | AMYLOID β REMOVAL TOOL, ORGANISM DERIVED LIQUID PURIFICATION SYSTEM, AMYLOID β REMOVAL METHOD AND AMYLOID β REMOVAL ADSORBENT |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0800862B1 (en) * | 1994-12-26 | 2002-02-27 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Adsorbent for endotoxin, tumor necrosis factor-alpha or interleukins, method for removal via adsorption, and adsorber |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56141832A (en) * | 1980-04-08 | 1981-11-05 | Asahi Chem Ind Co Ltd | Adsorbent for purification of blood |
| JPS5886169A (en) * | 1981-11-16 | 1983-05-23 | 株式会社ミドリ十字 | Filter of blood |
| JPS61264260A (en) * | 1985-05-17 | 1986-11-22 | Rikagaku Kenkyusho | Method for removing protein by porous aldehyde high-polymer material |
| JPS62261367A (en) * | 1986-05-07 | 1987-11-13 | 旭化成株式会社 | Adsorbent for beta 2 microglobulin |
| JPS6319154A (en) * | 1986-07-10 | 1988-01-26 | 東京有機化学工業株式会社 | Beta 2-microglobulin adsorbent |
-
1986
- 1986-11-11 JP JP61268054A patent/JPH0611332B2/en not_active Expired - Lifetime
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56141832A (en) * | 1980-04-08 | 1981-11-05 | Asahi Chem Ind Co Ltd | Adsorbent for purification of blood |
| JPS5886169A (en) * | 1981-11-16 | 1983-05-23 | 株式会社ミドリ十字 | Filter of blood |
| JPS61264260A (en) * | 1985-05-17 | 1986-11-22 | Rikagaku Kenkyusho | Method for removing protein by porous aldehyde high-polymer material |
| JPS62261367A (en) * | 1986-05-07 | 1987-11-13 | 旭化成株式会社 | Adsorbent for beta 2 microglobulin |
| JPS6319154A (en) * | 1986-07-10 | 1988-01-26 | 東京有機化学工業株式会社 | Beta 2-microglobulin adsorbent |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020081165A (en) * | 2018-11-20 | 2020-06-04 | 株式会社クレハ | AMYLOID β REMOVAL TOOL, ORGANISM DERIVED LIQUID PURIFICATION SYSTEM, AMYLOID β REMOVAL METHOD AND AMYLOID β REMOVAL ADSORBENT |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63122463A (en) | 1988-05-26 |
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