JP2584261B2 - Hemoglobin adsorbent - Google Patents
Hemoglobin adsorbentInfo
- Publication number
- JP2584261B2 JP2584261B2 JP62308903A JP30890387A JP2584261B2 JP 2584261 B2 JP2584261 B2 JP 2584261B2 JP 62308903 A JP62308903 A JP 62308903A JP 30890387 A JP30890387 A JP 30890387A JP 2584261 B2 JP2584261 B2 JP 2584261B2
- Authority
- JP
- Japan
- Prior art keywords
- hemoglobin
- adsorbent
- blood
- present
- adsorption
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、ヘモグロビンを選択的に吸着することので
きる吸着剤に関する。さらに詳しくは、体外循環により
血液中の遊離ヘモグロビンを吸着除去して生体に対して
ヘモグロビンが有害な作用を引き起こすのを防止する目
的に好適な吸着剤に関する。Description: TECHNICAL FIELD The present invention relates to an adsorbent capable of selectively adsorbing hemoglobin. More specifically, the present invention relates to an adsorbent suitable for the purpose of adsorbing and removing free hemoglobin in blood by extracorporeal circulation to prevent hemoglobin from causing harmful effects on living bodies.
人工腎臓や人工心肺のような血液体外循環装置を用い
て治療を行うと、しばしば溶血を起こして種々の合併症
を引き起こすことがある。この原因の一つは、溶血によ
り血液中に遊出してきた遊離ヘモグロビンによるもので
ある。すなわち、遊離ヘモグロビンは血液中でハプトグ
ロビンと結合して複合体となり、網内系で処理される
が、溶血量が多くて処理容量を超えるとヘモグロビンが
組織毒性物質として作用し、腎不全等を引き起こす。ま
た、自己免疫疾患の一種である溶血性貧血によっても同
様に血液中に多量のヘモグロビンが遊出して種々の障害
を起こす。このような事態が生じた場合に、遊離ヘモグ
ロビンを血液中から除去できれば障害を防ぐことができ
ると考えられる。血液中の有害物質を除去する手段とし
て従来より知られているのは、半透膜を使用する方法と
吸着剤を使用する方法であるが、ヘモグロビンについて
は吸着による方法がわずかに検討されているのみであっ
た。When treatment is performed using a blood extracorporeal circulation device such as an artificial kidney or a cardiopulmonary bypass, hemolysis often occurs and various complications may occur. One of the causes is due to free hemoglobin that has migrated into the blood due to hemolysis. In other words, free hemoglobin binds to haptoglobin in blood to form a complex and is processed in the reticulum system, but when hemolysis is large and the processing capacity is exceeded, hemoglobin acts as a histotoxic substance, causing renal failure etc. . Similarly, hemolytic anemia, which is a type of autoimmune disease, causes a large amount of hemoglobin to migrate into the blood and cause various disorders. If such a situation occurs, it would be possible to prevent damage if free hemoglobin could be removed from the blood. Conventionally known methods for removing harmful substances in the blood are a method using a semipermeable membrane and a method using an adsorbent.However, for hemoglobin, a method by adsorption has been slightly studied. Was only.
血液中の遊離ヘモグロビンを除去するための吸着剤と
して従来より知られていたのは、不溶性の担体にハプト
グロビンを結合したものである。すなわち、ハプトグロ
ビンが選択的にヘモグロビンと結合する性質を有するこ
とを利用してヘモグロビンを吸着するものである。そし
てこのような吸着剤は、特公昭55−4417号公報および特
公昭56−51780号公報に開示されている。A conventionally known adsorbent for removing free hemoglobin in blood is one in which haptoglobin is bound to an insoluble carrier. That is, hemoglobin is adsorbed by utilizing the fact that haptoglobin has a property of selectively binding to hemoglobin. Such an adsorbent is disclosed in JP-B-55-4417 and JP-B-56-51780.
不溶性の担体にハプトグロビンを結合した従来の吸着
剤は、生化学的な反応を利用したものであるのでヘモグ
ロビンの選択的吸着という点では優れている。しかしハ
プトグロビンはヒトの血漿等から分離精製して得られる
生体由来の物質であるため、これを不活性化することな
く担体に固定するには高度の技術が必要であり、現状で
は実用性のある方法は見出されていない。しかも例え活
性を維持したままで固定できたとしても、時間の経過と
ともに活性が低下する現象があり、実用化には問題があ
った。また、吸着剤を医療用途に使用する場合には、予
め滅菌しておく必要があるが、ハプトグロビンは滅菌を
行うと失活してしまうので、滅菌ができないという致命
的な欠点を有していた。The conventional adsorbent in which haptoglobin is bound to an insoluble carrier is excellent in terms of selective adsorption of hemoglobin since it utilizes a biochemical reaction. However, since haptoglobin is a biological substance obtained by separation and purification from human plasma, etc., it requires advanced technology to fix it to a carrier without inactivating it, and at present it is practical No method has been found. Moreover, even if the activity can be fixed while maintaining the activity, there is a phenomenon that the activity decreases with the passage of time, and there is a problem in practical use. In addition, when the adsorbent is used for medical applications, it is necessary to sterilize the adsorbent in advance, but haptoglobin has a fatal disadvantage that sterilization cannot be performed because it is inactivated when sterilized. .
本発明の目的は、製造が容易でヘモグロビンを選択的
に吸着できる吸着剤を提供することにある。本発明の他
の目的は、滅菌の可能なヘモグロビン吸着剤を提供する
ことにある。An object of the present invention is to provide an adsorbent that can be easily produced and can selectively adsorb hemoglobin. It is another object of the present invention to provide a sterilizable hemoglobin adsorbent.
本発明者らは種々の検討を行った結果、平均細孔径が
120Å以上の多孔性ガラスが、上記の目的を達成し得る
ものであることを見出した。すなわち本発明は、平均細
孔径が120Å以上で、且つ500Å以下の多孔性ガラスから
なることを特徴とするヘモグロビンの吸着剤である。The present inventors have conducted various studies and found that the average pore diameter is
It has been found that a porous glass of 120 ° or more can achieve the above object. That is, the present invention is an adsorbent for hemoglobin, comprising a porous glass having an average pore diameter of 120 ° or more and 500 ° or less.
多孔性ガラスがヘモグロビンの優れた吸着剤となる理
由については明確ではないが、表面のシラノール基がヘ
モグロビンと何らかの相互作用を起こすためと考えられ
る。また、多孔性ガラスは、平均細孔径が120Å以上の
ときに良好な吸着能力を示すが、この理由は細孔径がこ
れよりも小さいとヘモグロビン分子が細孔の中へ入りに
くく、したがって吸着されにくいためと思われる。ま
た、細孔径の上限については特に明確な限界はないが、
あまり細孔径が大きくなると総蛋白質の吸着が多くなる
とともにヘモグロビンの吸着能力が低下するので、500
Å以下のものが好ましい。The reason why porous glass is an excellent adsorbent for hemoglobin is not clear, but it is considered that silanol groups on the surface cause some interaction with hemoglobin. In addition, porous glass shows good adsorption capacity when the average pore diameter is 120 ° or more, and the reason is that if the pore diameter is smaller than this, it is difficult for hemoglobin molecules to enter the pores, and therefore it is difficult to be adsorbed It seems to be because. In addition, there is no particular limit on the upper limit of the pore diameter,
If the pore size is too large, the total protein adsorption increases and the hemoglobin adsorption capacity decreases.
Å The following are preferred.
本発明の吸着剤は、これをカラムに充填してヘモグロ
ビンを含有する溶液（例えば血液等）と接触させること
により、ヘモグロビンが吸着除去される。The adsorbent of the present invention is packed in a column and brought into contact with a hemoglobin-containing solution (eg, blood) to adsorb and remove hemoglobin.
本発明において使用される多孔性ガラスは、アルカリ
ホウケイ酸ガラスを溶融成形した後、転移温度域で熱処
理することによって得られる微細分相ガラスをさらに酸
処理することによって、一方の相を溶解して細孔を形成
したものであり、一般にカラムクロマトグラフィなどの
分野において多用されている。本発明においては、この
ような通常の製品をそのまま使用することができる。そ
の形状は特に限定されるものではなく、破砕状のものも
ビーズ状のものも使用することができる。また、粒径に
ついても特に制限はない。The porous glass used in the present invention is obtained by melt-forming an alkali borosilicate glass, and further performing an acid treatment on a fine phase-separated glass obtained by heat treatment in a transition temperature range, thereby dissolving one phase. It has pores and is generally used in fields such as column chromatography. In the present invention, such ordinary products can be used as they are. The shape is not particularly limited, and crushed or bead-shaped ones can be used. There is no particular limitation on the particle size.
本発明の吸着剤は、特に血液の体外循環による血液中
のヘモグロビンの除去に有用であるが、この場合には、
吸着剤は血液の入口と出口を有するカラムに充填し、こ
れに血液を連続的に流すことによって、ヘモグロビンを
吸着する。血液は吸着剤と接触させる際に全血を直接接
触させることもできるが、血漿分離器で血漿と血球とを
分離して血漿のみを吸着剤と接触させ、処理した血漿を
再び血球と混合して体内に返すようにしてもよい。また
体外循環においては、吸着剤はそれだけを単独で用いる
こともできるが、人工腎臓や人工心肺など他の血液体外
循環装置と併用することもできる。このときは、人工腎
臓や人工心肺の後に吸着カラムを設けると効果的であ
り、さらには人工腎臓または人工心肺と吸着剤とを一体
化して用いてもよい。The adsorbent of the present invention is particularly useful for removing hemoglobin in blood by extracorporeal circulation of blood.
The adsorbent adsorbs hemoglobin by filling a column having an inlet and an outlet for blood and continuously flowing blood therethrough. When blood is brought into contact with the adsorbent, whole blood can be brought into direct contact with the adsorbent.However, plasma and blood cells are separated by a plasma separator, only the plasma is brought into contact with the adsorbent, and the treated plasma is mixed with the blood cells again. May be returned to the body. In the extracorporeal circulation, the adsorbent alone can be used alone, but it can also be used in combination with another extracorporeal blood circulation device such as an artificial kidney or a heart-lung machine. At this time, it is effective to provide an adsorption column after the artificial kidney or the heart-lung machine, and furthermore, the artificial kidney or the heart-lung machine and the adsorbent may be used integrally.
さらに医療用途に用いる場合、吸着剤は通常は滅菌し
てから使用するが、滅菌方法としては高圧蒸気滅菌ある
いは放射線滅菌が好ましい。Further, when used in medical applications, the adsorbent is usually used after sterilization, and the sterilization method is preferably high-pressure steam sterilization or radiation sterilization.
以下具体的実施例により本発明をさらに詳細に説明す
る。Hereinafter, the present invention will be described in more detail with reference to specific examples.
実施例 １ 市販の多孔性ガラス（和光純薬製、商品名FPG−250、
平均細孔径223Å）0.2gを4mlの溶血血漿（遊離ヘモグロ
ビン濃度205.3mg/dl,総蛋白質濃度6.5g/dl）と混合し、
室温で２時間振盪して、遊離ヘモグロビンを吸着させ
た。そして血漿と吸着剤とを分離して血漿中のヘモグロ
ビン濃度を測定したところ、119.7mg/dlであった。すな
わち、ヘモグロビンの初期濃度との差85.6mg/dlが吸着
除去されており、41.7％のヘモグロビンが吸着されたこ
とになる。また、吸着試験後の血漿中の総蛋白質濃度は
5.5g/dlであり、総蛋白質としては15.4％が吸着された
ことになる。この結果から、本発明の吸着剤はヘモグロ
ビンを効率よく吸着できることがわかる。Example 1 Commercially available porous glass (manufactured by Wako Pure Chemical, trade name: FPG-250,
0.2 g of average pore size 223Å) was mixed with 4 ml of hemolyzed plasma (free hemoglobin concentration 205.3 mg / dl, total protein concentration 6.5 g / dl),
Free hemoglobin was adsorbed by shaking at room temperature for 2 hours. Then, the plasma and the adsorbent were separated, and the hemoglobin concentration in the plasma was measured, and it was 119.7 mg / dl. That is, the difference of 85.6 mg / dl from the initial concentration of hemoglobin was adsorbed and removed, which means that 41.7% of hemoglobin was adsorbed. In addition, the total protein concentration in plasma after the adsorption test is
5.5 g / dl, indicating that 15.4% of the total protein was adsorbed. These results show that the adsorbent of the present invention can adsorb hemoglobin efficiently.
比較例 １ 多孔性ガラスFPG−700（平均細孔径700Å）を用いて
実施例１と同様の吸着試験を実施したところ、ヘモグロ
ビンの吸着率は8.1％であり、総蛋白質吸着率は9.2％で
あった。Comparative Example 1 An adsorption test similar to that of Example 1 was performed using a porous glass FPG-700 (average pore diameter: 700 mm). As a result, the hemoglobin adsorption rate was 8.1%, and the total protein adsorption rate was 9.2%. Was.
比較例 ２ 多孔性ガラスFPG−100（平均細孔径97Å）を用いて実
施例１と同様な吸着試験を実施した。その結果、ヘモグ
ロビンの吸着率は3.5％であり、総蛋白質吸着率は4.3％
であった。Comparative Example 2 An adsorption test similar to that of Example 1 was performed using porous glass FPG-100 (average pore diameter: 97 °). As a result, the hemoglobin adsorption rate was 3.5%, and the total protein adsorption rate was 4.3%.
Met.
実施例１と比較例1,比較例２との結果を比較すると、
多孔性ガラスの平均細孔径がヘモグロビンの吸着に大き
く影響しており、平均細孔径が120Åよりも小さいと吸
着能力が大きく低下しており、平均細孔径が120〜500Å
のときに最良の結果が得られることがわかる。Comparing the results of Example 1 with Comparative Examples 1 and 2,
The average pore size of the porous glass greatly affects the adsorption of hemoglobin, and if the average pore size is smaller than 120 mm, the adsorption capacity is greatly reduced, and the average pore size is 120 to 500 mm.
It can be seen that the best result is obtained when.
本発明の吸着剤を使用すれば、血液中の遊離ヘモグロ
ビンを効率よくかつ選択的に吸着除去することができ
る。また、高圧蒸気滅菌や放射線滅菌などの方法により
滅菌を行うことができるので、医療用途に適している。By using the adsorbent of the present invention, free hemoglobin in blood can be efficiently and selectively adsorbed and removed. In addition, since sterilization can be performed by a method such as high-pressure steam sterilization or radiation sterilization, it is suitable for medical use.
さらに、本発明の吸着剤は市販の多孔性ガラスをその
まま使用することができるので、製造が容易で経済的に
も優れている。Furthermore, since the adsorbent of the present invention can use a commercially available porous glass as it is, it is easy to manufacture and economically excellent.
Claims (1)
の多孔性ガラスからなることを特徴とするヘモグロビン
の吸着剤。1. A hemoglobin adsorbent comprising a porous glass having an average pore diameter of not less than 120 ° and not more than 500 °.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62308903A JP2584261B2 (en) | 1987-12-07 | 1987-12-07 | Hemoglobin adsorbent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62308903A JP2584261B2 (en) | 1987-12-07 | 1987-12-07 | Hemoglobin adsorbent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01148267A JPH01148267A (en) | 1989-06-09 |
| JP2584261B2 true JP2584261B2 (en) | 1997-02-26 |
Family
ID=17986655
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62308903A Expired - Fee Related JP2584261B2 (en) | 1987-12-07 | 1987-12-07 | Hemoglobin adsorbent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2584261B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8241819B2 (en) | 2002-04-05 | 2012-08-14 | Smart Holograms Limited | Method for forming a volume holographic sensor in a porous medium |
-
1987
- 1987-12-07 JP JP62308903A patent/JP2584261B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8241819B2 (en) | 2002-04-05 | 2012-08-14 | Smart Holograms Limited | Method for forming a volume holographic sensor in a porous medium |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH01148267A (en) | 1989-06-09 |
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