JPH07185332A - Novel endotoxine adsorbent - Google Patents
Novel endotoxine adsorbentInfo
- Publication number
- JPH07185332A JPH07185332A JP5337283A JP33728393A JPH07185332A JP H07185332 A JPH07185332 A JP H07185332A JP 5337283 A JP5337283 A JP 5337283A JP 33728393 A JP33728393 A JP 33728393A JP H07185332 A JPH07185332 A JP H07185332A
- Authority
- JP
- Japan
- Prior art keywords
- glutaraldehyde
- cross
- endotoxin
- linked polymer
- water
- 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
Landscapes
- External Artificial Organs (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、ポリアリルアミンの架
橋ポリマーからなる新規なエンドトキシン吸着材に関す
る。TECHNICAL FIELD The present invention relates to a novel endotoxin adsorbent comprising a crosslinked polymer of polyallylamine.
【０００２】[0002]
【従来の技術】エンドトキシンは、リポ多糖であり代表
的な発熱性物質である。エンドトキシンにより汚染され
た血液、輸液、注射薬が体内に入ると発熱やショックな
どの副作用をひき起すため医薬品のエンドトキシンによ
る汚染は厳しく検査されている。そのため製薬用の水、
注射器の洗浄水、手術室で用いられる水などは、これま
でイオン交換水を蒸留し、さらに殺菌して密封されてお
り、特別に薬品メーカーから購入して使用し、残った水
は廃棄するといった無駄とコストがかかるものであっ
た。従って手軽にエンドトキシンフリーの水を得ること
ができるシステムの開発が待たれているのが現状であ
る。2. Description of the Related Art Endotoxin is a lipopolysaccharide and is a typical pyrogenic substance. When blood, infusions, or injections contaminated with endotoxin enter the body, side effects such as fever and shock are caused, and thus endotoxin contamination of pharmaceuticals is strictly tested. Therefore, pharmaceutical water,
The water used to wash syringes, water used in the operating room, etc. has been distilled by ion-exchanged water, sterilized, and sealed. It is specially purchased from a drug manufacturer for use, and the remaining water is discarded. It was wasteful and costly. Therefore, at present, the development of a system that can easily obtain endotoxin-free water is awaited.
【０００３】従来、エンドトキシンを除去する手段とし
ては、逆浸透膜や濾過膜を使用する方法、又は特開平１
−２４２１０５号公報に記載されているようなポリメチ
ルメタクリレート系樹脂の多孔質体による除去法が知ら
れている。しかしながら、これらの方法によっても、前
者は血液等には適用できず、又、後者は、タンパク質中
のエンドトキシン除去はできないという問題点がある。Conventionally, as a means for removing endotoxin, a method using a reverse osmosis membrane or a filtration membrane, or Japanese Patent Laid-Open No.
There is known a method for removing a polymethylmethacrylate resin with a porous body as described in Japanese Patent Publication No. 242105. However, even by these methods, the former cannot be applied to blood and the like, and the latter cannot remove endotoxin in a protein.
【０００４】[0004]
【発明が解決しようとする課題】本発明の目的は、エン
ドトキシンの吸着性能に優れた吸着材を提供することに
よってエンドトキシンフリーの水を効率よく低コストで
製造することを可能にし、又、タンパク質中のエンドト
キシンを低コストで除去することを可能にしようとする
ものである。DISCLOSURE OF THE INVENTION An object of the present invention is to provide an adsorbent excellent in endotoxin adsorption performance, thereby making it possible to produce endotoxin-free water efficiently and at low cost. It is intended to enable low-cost removal of endotoxins of.
【０００５】[0005]
【課題を解決するための手段】本発明者は鋭意検討した
結果、ポリアリルアミンの架橋ポリマーがエンドトキシ
ンの吸着性能に優れることを見出し本発明に到達した。Means for Solving the Problems As a result of intensive studies, the present inventors have found that a crosslinked polymer of polyallylamine is excellent in endotoxin adsorption performance and arrived at the present invention.
【０００６】本発明は、数平均分子量１，０００〜１
０，０００のポリアリルアミンをグルタルアルデヒドに
より架橋処理した架橋ポリマーからなることを特徴とす
る新規なエンドトキシン吸着材にある。The present invention has a number average molecular weight of 1,000 to 1.
It is a novel endotoxin adsorbent characterized by comprising a cross-linked polymer obtained by cross-linking 10,000 polyallylamine with glutaraldehyde.
【０００７】以下、本発明を具体的に説明する。本発明
を実施するに際して用いられるポリアリルアミンとは一
般式（１）で示されるアリルアミンの塩酸塩をその繰り
返し単位とするものである。The present invention will be specifically described below. The polyallylamine used in the practice of the present invention has an allylamine hydrochloride represented by the general formula (1) as its repeating unit.
【０００８】[0008]
【化１】 [Chemical 1]
【０００９】又、本発明で用いられる架橋ポリマーはか
かるポリアリルアミンをグルタルアルデヒドにより架橋
処理したものである。この架橋ポリマーはビーズ状であ
ることが好ましく、平均粒子徑は２０〜５００ミクロ
ン、より好ましくは５０〜３００ミクロンである。The crosslinked polymer used in the present invention is such a polyallylamine crosslinked with glutaraldehyde. The crosslinked polymer is preferably in the form of beads and has an average particle size of 20 to 500 microns, more preferably 50 to 300 microns.
【００１０】架橋ポリマー中のポリアリルアミンとグル
タルアルデヒドの組成比としてはポリアリルアミン／グ
ルタルアルデヒド＝９０〜４０／１０〜６０重量比、よ
り好ましくは８０〜５０／２０〜５０重量比である。グ
ルタルアルデヒドの量が１０重量％未満であると架橋ポ
リマーが水により膨潤しすぎてカラムに詰めて通水する
ことが困難となる傾向を示し、又、６０重量％を超える
とエンドトキシン吸着能が十分でなくなる傾向となるた
め好ましくない。The composition ratio of polyallylamine and glutaraldehyde in the crosslinked polymer is polyallylamine / glutaraldehyde = 90 to 40/10 to 60 weight ratio, more preferably 80 to 50/20 to 50 weight ratio. If the amount of glutaraldehyde is less than 10% by weight, the cross-linked polymer tends to swell too much with water, making it difficult to pack water in the column and pass it. If it exceeds 60% by weight, endotoxin adsorption capacity is sufficient. It is not preferable because it tends to disappear.
【００１１】本発明を実施するに際して用いるポリアリ
ルアミンの塩酸塩は市販されているものを使用すること
ができ、例えば日東紡績株式会社製のポリアリルアミン
塩酸塩ＰＡＡ・ＨＣｌ−３Ｓ（数平均分子量 約１０，
０００）、ＰＡＡ・ＨＣｌ−１０Ｓ（数平均分子量 約
５０，０００）を使用することができる。The polyallylamine hydrochloride used in carrying out the present invention may be a commercially available product. For example, polyallylamine hydrochloride PAA.HCl-3S (number average molecular weight of about 10) manufactured by Nitto Boseki Co., Ltd. ，
000) and PAA.HCl-10S (number average molecular weight of about 50,000) can be used.
【００１２】[0012]
【実施例】以下、実施例によって本発明を具体的に説明
する。エンドトキシン吸着量（ｎｇ／ｇポリマー）はグ
ルタルアルデヒドで架橋処理したビーズ状ポリアリルア
ミン塩酸塩をカラムクロマト用ガラス管につめ、１００
０〜２０００ｐｇ／ｍｌのエンドトキシンを含有するイ
オン交換水を通水し、一定時間毎にエンドトキシン量を
カラム入口、出口の水について求め、総吸着量を求め
た。エンドトキシン量は、和光純薬（株）のリムルスＨ
ＳＪ−IIテストワコーを用い、比濁法により定量した。EXAMPLES The present invention will be specifically described below with reference to examples. The amount of adsorbed endotoxin (ng / g polymer) was 100 when the bead-shaped polyallylamine hydrochloride cross-linked with glutaraldehyde was packed in a glass tube for column chromatography.
Ion-exchanged water containing 0 to 2000 pg / ml endotoxin was passed through, and the amount of endotoxin was determined for the water at the column inlet and outlet at regular time intervals to determine the total adsorption amount. The amount of endotoxin is Limulus H from Wako Pure Chemical Industries, Ltd.
SJ-II Test Wako was used and quantified by the turbidimetric method.
【００１３】［実施例１］数平均分子量約１０，０００
のポリアリルアミン塩酸塩（日東紡績（株）製ＰＡＡ・
ＨＣｌ−３Ｓ）５０ｇをエチルアルコール５００ｍｌに
溶解し、１００ｒｐｍで攪拌しながらグルタルアルデヒ
ド２５％水溶液を１００ｍｌ／時間の速さで１００ｍｌ
添加した。ポリアリルアミン塩酸塩はグルタルアルデヒ
ドにより架橋し、ビーズ状の形態で沈澱した。沈澱物を
エチルアルコールでよく洗浄し、７０℃で一夜真空乾燥
してビーズ状架橋ポリマーを得た。このビーズ状架橋ポ
リマー２０ｇを直径２ｃｍ、長さ３５ｃｍのガラス製ク
ロマト管に詰め、１，０００〜２，０００Ｐｇ／ｍｌの
エンドトキシンを含むイオン交換水を通水し、総吸着量
を求めたところ１０，０００ｎｇ／ｇポリマーであっ
た。Example 1 Number average molecular weight of about 10,000
Polyallylamine hydrochloride (PAA manufactured by Nitto Boseki Co., Ltd.)
50 g of HCl-3S) is dissolved in 500 ml of ethyl alcohol and 100 ml of a 25% aqueous solution of glutaraldehyde is stirred at 100 rpm at a rate of 100 ml / hour.
Was added. The polyallylamine hydrochloride was crosslinked with glutaraldehyde and precipitated in the form of beads. The precipitate was thoroughly washed with ethyl alcohol and dried under vacuum at 70 ° C. overnight to obtain a bead-shaped crosslinked polymer. 20 g of this bead-shaped crosslinked polymer was packed in a glass chromatographic tube having a diameter of 2 cm and a length of 35 cm, ion-exchanged water containing 1,000 to 2,000 Pg / ml of endotoxin was passed, and the total adsorption amount was determined to be 10 1,000 ng / g polymer.
【００１４】［実施例２］ポリアリルアミンに対するグ
ルタルアルデヒドの添加量を表１に示すように示すよう
に種々変更する以外は実施例１と同様の方法で実験を行
い、エンドトキシンの総吸着量を求めた。結果を表１に
示した。表１の結果から明らかなように、グルタルアル
デヒドの添加量が１０重量％未満だと架橋ポリマーが水
により著しく膨潤し、通水不能となることがわかる。
又、グルタルアルデヒドの添加量が６０重量％以上だと
架橋ポリマーの水による膨潤が殆どなくエンドトキシン
の吸着量がそれほどでもないことがわかる。Example 2 An experiment was conducted in the same manner as in Example 1 except that the amount of glutaraldehyde added to polyallylamine was changed as shown in Table 1 to obtain the total amount of endotoxin adsorbed. It was The results are shown in Table 1. As is clear from the results in Table 1, it can be seen that when the amount of glutaraldehyde added is less than 10% by weight, the cross-linked polymer swells significantly with water and water cannot pass through.
Further, it can be seen that when the amount of glutaraldehyde added is 60% by weight or more, the cross-linked polymer hardly swells with water and the amount of endotoxin adsorbed is not so large.
【００１５】[0015]
【表１】 [Table 1]
【００１６】[0016]
【発明の効果】本発明のエンドトキシン吸着材は上述し
た如き特定の架橋ポリマーからなるため、エンドトキシ
ンの吸着性能に優れ、エンドトキシンフリーの水を効率
よく低コストで製造することが可能であり、又、タンパ
ク質中のエンドトキシンを低コストで除去することが可
能であるなど優れた効果を奏する。EFFECT OF THE INVENTION Since the endotoxin adsorbent of the present invention is composed of the specific cross-linked polymer as described above, it has excellent adsorbability for endotoxin, and can efficiently produce endotoxin-free water at low cost. It has excellent effects such as the ability to remove endotoxin from proteins at low cost.
Claims (2)
０のポリアリルアミンをグルタルアルデヒドにより架橋
処理した架橋ポリマーからなることを特徴とする新規な
エンドトキシン吸着材。1. A number average molecular weight of 1,000 to 100,00.
A novel endotoxin adsorbent, which comprises a crosslinked polymer obtained by crosslinking polyallylamine of No. 0 with glutaraldehyde.
０ミクロンである請求項１記載の新規なエンドトキシン
吸着材。2. The average particle size of the crosslinked polymer is 20 to 50.
The novel endotoxin adsorbent according to claim 1, which is 0 micron.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5337283A JPH07185332A (en) | 1993-12-28 | 1993-12-28 | Novel endotoxine adsorbent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5337283A JPH07185332A (en) | 1993-12-28 | 1993-12-28 | Novel endotoxine adsorbent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH07185332A true JPH07185332A (en) | 1995-07-25 |
Family
ID=18307159
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5337283A Pending JPH07185332A (en) | 1993-12-28 | 1993-12-28 | Novel endotoxine adsorbent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07185332A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020529917A (en) * | 2017-08-01 | 2020-10-15 | インストラクション・ゲーエムベーハーＩｎｓｔｒａｃｔｉｏｎ Ｇｍｂｈ | Removal of bacteria from drinking water by filtration |
-
1993
- 1993-12-28 JP JP5337283A patent/JPH07185332A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020529917A (en) * | 2017-08-01 | 2020-10-15 | インストラクション・ゲーエムベーハーＩｎｓｔｒａｃｔｉｏｎ Ｇｍｂｈ | Removal of bacteria from drinking water by filtration |
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