JPS59184134A - Production of carrier for immobilizing physiologically active substance - Google Patents
Production of carrier for immobilizing physiologically active substanceInfo
- Publication number
- JPS59184134A JPS59184134A JP5690983A JP5690983A JPS59184134A JP S59184134 A JPS59184134 A JP S59184134A JP 5690983 A JP5690983 A JP 5690983A JP 5690983 A JP5690983 A JP 5690983A JP S59184134 A JPS59184134 A JP S59184134A
- Authority
- JP
- Japan
- Prior art keywords
- physiologically active
- active substance
- carrier
- immobilized
- group
- 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.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は医療用、あるいは医療用製剤等の製造に際して
有効に用い得る滅菌された生理活性物質固定化担体の製
造方法に関するものである。生 −理活性物質固定化担
体とは、組織、細胞、細胞内組織、酵素抗原、抗体、抗
原抗体複合物、補体等の、蛋白質、多糖類、核酸、脂質
及びこれらの複合物などの生理活性物質を不溶性の担体
表面に固定化し、該生理活性物質固有の中管学的反応を
担体上で行なわせるものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a sterilized physiologically active substance-immobilized carrier that can be effectively used in the production of medical products or medical preparations. Physiologically active substance-immobilized carriers refer to physiologically active substance immobilization carriers such as tissues, cells, intracellular tissues, enzyme antigens, antibodies, antigen-antibody complexes, complements, proteins, polysaccharides, nucleic acids, lipids, and complexes thereof. An active substance is immobilized on the surface of an insoluble carrier, and a mesovascular reaction specific to the physiologically active substance is caused to occur on the carrier.
従来よシ生理活性物質固有の生物学的反応を行わせるた
めアガロース及びアガロースに種々の生理活性物質を固
定化したものが分離、分析用に広く使用されている。し
かしながら、これらは、固定化された生理活性物質が本
来、良好な耐熱性を有する場合を除き、一般的なエチレ
ンオキシドガス滅菌、湿熱滅菌条件において失活するた
め通常滅菌が不必要な場合に限定して用いられて＞、６
、滅菌が必要な医療用、あるいは医療用製剤の製造とい
う目的にはほとんど応用されていない。Conventionally, agarose and various physiologically active substances immobilized on agarose have been widely used for separation and analysis in order to carry out biological reactions specific to physiologically active substances. However, these methods are limited to cases where sterilization is not necessary because they are inactivated under general ethylene oxide gas sterilization and moist heat sterilization conditions, unless the immobilized physiologically active substance inherently has good heat resistance. used>,6
, it is rarely applied for medical purposes that require sterilization or for the production of medical preparations.
本発明者らは医療用あるいは医療用製剤の製造に使用す
ることのできる生理活性物質固定化担体の製造方法を提
供するため鋭意研究を重ねた結果、本来、湿熱滅菌によ
シ変性失活する生理活性物質に、耐滅菌性を付与するた
めには、少なくとも生理活性物質を固定化する担体が湿
熱滅菌条件で変形しないことが必要であることを見出し
、本発明に到達したものである。すなわち本発明は、室
温における線膨張係数が３ ｘ １０ ’ｄｅｇ ”以
下、室温におけるヤング率がＩ Ｘ １０１１ｄｙｎｅ
ｓ ｃｍ−２以上で、かつ構成素材の吸水率が２０チ以
下の多孔性担体上に生理活性物質を固定化し、しかる後
に温熱滅菌することを特徴とする生理活性物質固定化担
体の製造方法である。The present inventors have conducted intensive research to provide a method for producing a physiologically active substance-immobilized carrier that can be used for medical purposes or in the production of medical preparations. The present invention was achieved based on the discovery that in order to impart sterilization resistance to a physiologically active substance, it is necessary that at least the carrier on which the physiologically active substance is immobilized does not deform under moist heat sterilization conditions. That is, the present invention has a linear expansion coefficient of 3 x 10 'deg'' or less at room temperature, and a Young's modulus of I x 1011 dyne at room temperature.
A method for producing a physiologically active substance-immobilized carrier, which comprises immobilizing a physiologically active substance on a porous carrier having a water absorption rate of s cm -2 or more and a constituent material having a water absorption rate of 20 cm or less, followed by heat sterilization. be.
本発明で用いる上述の条件を満足する多孔体の構成素材
としては金属、ガラス、アルミナ、シリカ等の無機物、
および湿熱滅菌温度以上のガラス転移温度（以下Ｔｇと
略す）を持つ有機体、および、これらの複合体がめげら
れる。線膨張′係数が３ Ｘ ］ ０−’ｄｅｇ ”を
越えるかめるいはヤング率がＩＸ Ｉ Ｏ” ｄｙｎｅ
ｓ ｃｍ−２未満、あるいは構成素材の吸水率が２０％
を越える担体は、湿熱滅菌条件において、吸水して膨潤
変形したシ、ｍ度、圧力により変形し、本目的には適さ
ない。たとえば、従来よシ類似した目的に使用されてき
たアガロースは吸水によ）膨潤し、またアガロース自身
のヤング率が小さく湿熱滅菌条件において変形するため
に固定化した生理活性物質が失活する。有機体は一般に
Ｔｇ前後で物性が大きく変化するので、室温で本発明の
条件を満足する場合でも、Ｔｇが湿熱滅菌温度よシ低い
ものでは、本発明の効果は満足に発揮されない。Materials for forming the porous body that satisfies the above conditions used in the present invention include metals, glass, inorganic materials such as alumina, and silica;
and organisms having a glass transition temperature (hereinafter abbreviated as Tg) higher than the moist heat sterilization temperature, and complexes thereof. dyne whose coefficient of linear expansion exceeds 3 x 0-'deg or whose Young's modulus is IX I O'dyne
less than s cm-2, or the water absorption rate of the constituent materials is 20%
Under moist heat sterilization conditions, carriers that absorb water, swell and deform, are deformed by pressure, and are not suitable for this purpose. For example, agarose, which has traditionally been used for similar purposes, swells due to water absorption, and the immobilized physiologically active substances are deactivated because the agarose itself has a small Young's modulus and deforms under moist heat sterilization conditions. Generally, the physical properties of an organism greatly change around the Tg, so even if the conditions of the present invention are satisfied at room temperature, the effects of the present invention will not be satisfactorily exhibited if the Tg is lower than the moist heat sterilization temperature.
また、多孔性担体は、生理活性物質を有効に固定化し、
かつ固定化された生理活性物質と％ぐれに反応する物質
の・接触を容易ならしめるために、平均細孔直−径が１
００ＯＸ以上で、かつ細孔容積が０、３ ｍｌ ？−”
以上の多孔体であることが望ましい。In addition, porous carriers can effectively immobilize physiologically active substances,
In addition, in order to facilitate contact between the immobilized physiologically active substance and the substance that reacts with a certain amount, the average pore diameter is 1.
00OX or more and the pore volume is 0.3 ml? −”
It is desirable that the porous body has the above-mentioned properties.
これらの条件を満足する多孔体としては、多孔性ガラス
、多孔性シリカ・アルミナ、多孔性アルミナ、多孔性金
属等があげられ、このうちでも特に多孔性ガラスが物理
的強度が良好で、細孔径の均一なものを得やすい点で最
も好ましい。生理活性物質固定化担体の形状としては、
粒子、繊維、シート、管状体等が適当でアシ、用途に応
じて使い分けるのが好ましい。特に、０．０５〜５ｍの
粒子状の形態を有するものが好ましい。Porous materials that satisfy these conditions include porous glass, porous silica/alumina, porous alumina, porous metal, etc. Among these, porous glass has particularly good physical strength and pore size. It is most preferable in that it is easy to obtain a uniform product. The shape of the physiologically active substance immobilized carrier is as follows:
It is preferable to use particles, fibers, sheets, tubular bodies, etc. depending on the type and purpose. In particular, those having a particle form of 0.05 to 5 m are preferred.
担体表面には化学結合可能な活性基がｌＸｌ０’ｍｏｌ
ｅｍ７２以上の濃度で存在することが好ましい。There are 1X10'mol of active groups on the surface of the carrier that can be chemically bonded.
Preferably, it is present at a concentration of em72 or higher.
活性基濃度が１ｘ １０ ’ｍｏｌｅｍ−２以下である
と、生理活性物質が有効に固定化されず、しかも耐滅菌
性が低下し、好ましくない。ここで言う化学結合可能な
活性基とは、アミノ基、カルボキシル基、アルデヒド基
、エポキシ基等で、蛋白質、多糖類、核酸等の生理活性
物質と共有結合を形成することが可能な置換基である。If the active group concentration is less than 1 x 10' molem-2, the physiologically active substance will not be effectively immobilized, and sterilization resistance will deteriorate, which is not preferable. The active groups that can be chemically bonded here include amino groups, carboxyl groups, aldehyde groups, epoxy groups, etc., and are substituents that can form covalent bonds with physiologically active substances such as proteins, polysaccharides, and nucleic acids. be.
これらは上述の担体に本来存在するか、あるいは表面処
理によシ担体表面に導入される。表面処理方法としては
、アぐノグロビルトリエトキシシラン等のシランカップ
リング剤によジアミノ基あるいはカルボキシル“基を導
入する方法、あるいは％開昭５７−１５０４３３号に開
示された例に代表されるようにカルボキシル基あるいは
アミノ基を有するポリマーを表面に被覆する方法があげ
られる。生理活性物質としては、組織、細胞、細胞内組
織、抗原、抗体、酵素、抗原抗体複合物、補体等の、蛋
白質、多糖類、核酸、脂質、及びこれらの複合物がめげ
られる。These may be present naturally in the above-mentioned carriers or may be introduced onto the carrier surface by surface treatment. Examples of surface treatment methods include a method of introducing a diamino group or a carboxyl group using a silane coupling agent such as agunoglobiltriethoxysilane, or the example disclosed in %Kokai No. 150433/1983. Examples of physiologically active substances include tissues, cells, intracellular tissues, antigens, antibodies, enzymes, antigen-antibody complexes, complements, etc. Includes proteins, polysaccharides, nucleic acids, lipids, and complexes thereof.
担体に生理活性物質を固定化する方法としては、担体の
エポキシ基あるいはアルデヒド基と生理活性物質のアミ
ノ基とを直接結合させる方法、あるいは担体上のカルボ
キシル基あるいはアミン基と生理活性物質とを１−エチ
ル−３−（３−ジメチルアミノプロビル）カルボジイミ
ド塩酸塩（ＥＤＣ）等の脱水縮合剤で結合する方法、担
体のカルボキシル基をＮ−ヒドロキシコハク酸イミド等
の活性エステルとし、これに生理活性物質を置換させる
方法等があげられる。また、担体と生理活性物質との間
を、ｔ−アミノカプロン酸やジアミノヘプタン、グルタ
ルアルデヒド等の低分子量の基を介して固定することも
できる。Methods for immobilizing a physiologically active substance on a carrier include a method in which an epoxy group or an aldehyde group on the carrier is directly bonded to an amino group of the physiologically active substance, or a method in which a carboxyl group or an amine group on the carrier and a physiologically active substance are bonded together. - A method of bonding with a dehydration condensation agent such as ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), a method in which the carboxyl group of the carrier is replaced with an active ester such as N-hydroxysuccinimide, and this has physiological activity. Examples include methods of substituting substances. Furthermore, the carrier and the physiologically active substance can be immobilized via a low molecular weight group such as t-aminocaproic acid, diaminoheptane, or glutaraldehyde.
このようにして％製された生理活性物質固定化担体は日
本薬局方に規定されるごとく、一般に１２１℃で２０分
間の加熱を行うが、場合によっては１１５℃、３０分間
、わるいは１２６℃１５分間の加熱が行われる。上述の
生理活性物質固定化担体は上記高温高圧蒸気雰囲気中で
も失活しない。上記湿熱滅菌された生理活性物質固定化
担体の第１の用途としては、治療用選択吸着剤があげら
れる。この場合の生理活性物質は治療しようとする疾患
によって適当なものを選択すれば良い。The physiologically active substance-immobilized carrier prepared in this way is generally heated at 121°C for 20 minutes as specified in the Japanese Pharmacopoeia, but in some cases it may be heated at 115°C for 30 minutes or even heated at 126°C for 15 minutes. Heating takes place for a minute. The above-mentioned physiologically active substance immobilized carrier does not become deactivated even in the above-mentioned high-temperature, high-pressure steam atmosphere. The first use of the moist heat sterilized physiologically active substance immobilized carrier is as a therapeutic selective adsorbent. In this case, the physiologically active substance may be selected appropriately depending on the disease to be treated.
例えば、自己免疫性溶血性貧血、糸球体腎炎、慢性関節
リウマチ、全身性紅斑性狼瘉等の自己免疫疾患では、自
己抗体あるいは免疫複合体が疾患原因物質であるので、
これらを血液中より除去する必要がある。これらの自己
抗体めるいは免疫複合体を除去するためには、これらと
特異的に結合すル５ｔａｐｈｙｌｏｃｏｃｃｕｓ ａｕ
ｒｅｕｓのある種の株が産生ずるプロティンＡ１ リン
パ球や血小板等の細胞壁に存在するＦＣレセプター、補
体Ｃ１成分、抗免疫グロブリン抗体等を担体に固定化し
たものを治療用選択吸着剤として使用する。また腎不全
患者においては、血液中の尿素が代謝されずに蓄積する
ので、尿素を分解する酵素であるウレアーゼを固定化し
た担体を治療用固定化酵素として使用することもできる
。さらに癌患者においては、癌細胞に対する免疫作用を
抑制するいくつかの因子が血液中に存在することが証明
されているが、これらの免疫抑制因子は抗体分画と抗原
の１万〜１０万位の分子量の蛋白質分画に存在するので
、これらの抗原に対する抗体、プロティンＡ１細胞壁Ｆ
ｃレセプター、抗免疫グロブリン抗体を固定化して治療
用選択吸着剤として使用する。第２の用途としては蛋白
質、核酸、多糖類、ホルモン、とタミン等の医薬品、あ
るいは医療用製剤原料の分離精＃あるいは合成を目的と
するアフイニチイクワマトグ２フィー用吸着剤、あるい
は固定化酵素があげられる。医薬品あるいは医療用製剤
は無菌状態に保たれねばならないので、本発明の生理活
性物質固定化担体は滅菌されているので、この目的に有
効に用い得る。この用途においても、分離精製、あるい
は合成しようとする目的物質に応じて固定化する生理活
性物質を選択して使用する。For example, autoantibodies or immune complexes are the causative agents of autoimmune diseases such as autoimmune hemolytic anemia, glomerulonephritis, rheumatoid arthritis, and systemic lupus erythematosus.
These need to be removed from the blood. In order to remove these autoantibodies or immune complexes, 5 taphylococcus au
Protein A1 produced by certain strains of S. reus FC receptors, complement C1 components, anti-immunoglobulin antibodies, etc. present in the cell walls of lymphocytes and platelets are immobilized on a carrier and used as a selective adsorbent for treatment. . Furthermore, in patients with renal failure, urea in the blood accumulates without being metabolized, so a carrier on which urease, an enzyme that decomposes urea, is immobilized can also be used as a therapeutic immobilized enzyme. Furthermore, in cancer patients, it has been proven that several factors that suppress the immune action against cancer cells are present in the blood, and these immunosuppressive factors are found in the antibody fraction and antigens in the 10,000 to 100,000 range. Antibodies against these antigens, protein A1 cell wall F
c receptor, anti-immunoglobulin antibodies are immobilized and used as a selective adsorbent for therapy. The second use is as an adsorbent for Affinichii Kumamatog 2 fee for the purpose of separating or synthesizing pharmaceuticals such as proteins, nucleic acids, polysaccharides, hormones, and tamins, or raw materials for medical preparations, or immobilization. Examples include enzymes. Since pharmaceuticals or medical preparations must be kept in a sterile state, the physiologically active substance-immobilized carrier of the present invention is sterile and can be effectively used for this purpose. In this application as well, the physiologically active substance to be immobilized is selected and used depending on the target substance to be separated and purified or synthesized.
以下実施例によシ本発明をさらに具体的に説明する。The present invention will be explained in more detail below using Examples.
（実施例）
平均細孔直径１ｃ＋ｓｏＬ細孔容積０．７９ｊｇ−１の
多孔性ガラス（平均粒径０．１５Ｍ、線膨張係数的２Ｘ
１０’ｄｅｇ’、−？／ダグ率７ ｘ １０” ｄｙｎ
ｅｓ鍔−２、吸水率１％以下） ？、 ト、ルエン中で
３−７ミノプロビルトリエトキシシランと反応させアミ
ノ基を導入した（アミノ基濃度８．４ ｘ １０−”ｍ
ｏｌｅ ｍ ”）０次に抗ヒトＩｇＧ抗体（マイルス社
Ｍ）を緩衝溶液中でＫＤＣを用いて脱水縮合させて固定
化した後、１２１℃、２０分間の湿熱滅菌を行なって本
発明の生理活性物質固定化担体（実施例１）を得た。(Example) Porous glass with an average pore diameter of 1c + soL pore volume of 0.79jg-1 (average particle size of 0.15M, linear expansion coefficient of 2X
10'deg', -? / Doug rate 7 x 10” dyn
es Tsuba-2, water absorption rate 1% or less)? Amino groups were introduced by reacting with 3-7minoprobyltriethoxysilane in toluene (amino group concentration 8.4 x 10-"m).
Next, an anti-human IgG antibody (Miles M) was immobilized by dehydration condensation using KDC in a buffer solution, and then sterilized with moist heat at 121°C for 20 minutes to obtain the biological activity of the present invention. A substance-immobilized carrier (Example 1) was obtained.
同様の方法で実施例１と同じ多孔性ガラスに、抗ヒトＩ
ｇＧ抗体のかわシにグリシンエテルエステルを結合した
ものを比較例１とした。Anti-human I
Comparative Example 1 was prepared by bonding glycine ether ester to the gG antibody.
ＣＮＢｒで活性化したアガロース（ファルマシア社製、
商品名ＣＮＢｒ−ａｃｔｉｖａｔｅｄ ５ｅｐｂａｒｏ
ｓｅ ４ Ｂ 、吸水率１００％以上）に実施例１と同
じ抗ヒトＩｇＧ抗体を結合したものを比較例２とした。Agarose activated with CNBr (manufactured by Pharmacia,
Product name CNBr-activated 5epbaro
Comparative Example 2 was prepared by binding the same anti-human IgG antibody as in Example 1 to se 4 B (water absorption rate of 100% or more).
温熱滅菌（１２１℃、２０ｍ１ｎ）前後の実施例１、比
較例１，２、それぞれ１２（乾燥重量）に対し１０ｄの
ヒトＩｇＧ溶液（＃度Ｉ Ｗ ｍｆ”、用７．４リン酸
塩緩衝液）を加え、３７℃で３時間振盪した。Example 1 and Comparative Examples 1 and 2 before and after thermal sterilization (121°C, 20ml), 10d of human IgG solution (# degree I W mf'', 7.4 phosphate buffer for each 12 (dry weight)) ) was added and shaken at 37°C for 3 hours.
３時間後のヒトエρ゛濃度を２８０鴎の吸光度よシ求め
、濃度の減少量力・ら吸着量を計算した。結果は表−１
に示すように、実施例１では湿熱滅菌前後で吸着量がほ
とんど変化せず、本発明の生理活性物質固定化担体が滅
菌された状態で有効であることが明らかである。これに
対して実施例１と同じ担体に抗体のかわシにグリシンエ
チルエステルを固定化した比較例１では、ヒ） ＩｇＧ
を全く吸着せず、実施例１におけるヒ）Ｉρの吸着が非
特異的なものではなく、抗体による特異的な結合である
ことが確認された。また、比較例２では担体が本発明の
条件を満足せず、湿熱滅菌によって、固定化された抗体
が変性失活したため、滅菌後はヒトＩｇＧを全く吸着し
なかった。The concentration of human flies after 3 hours was calculated from the absorbance of 280 seaweed, and the amount of adsorption was calculated from the amount of decrease in concentration. The results are in Table-1
As shown in Example 1, the amount of adsorption hardly changed before and after moist heat sterilization, and it is clear that the physiologically active substance-immobilized carrier of the present invention is effective in a sterilized state. On the other hand, in Comparative Example 1, in which glycine ethyl ester was immobilized on the antibody base on the same carrier as in Example 1, IgG
It was confirmed that the adsorption of Iρ in Example 1 was not non-specific but specific binding by the antibody. Furthermore, in Comparative Example 2, the carrier did not satisfy the conditions of the present invention, and the immobilized antibody was denatured and inactivated by moist heat sterilization, so it did not adsorb human IgG at all after sterilization.
表−１ ヒトエ頗吸着：１ｌ（ｑ／ｆ担体） 実施例１ ０，９３ ０．８７ 比較例】 ０ − 比較例２ ５．０ ０Table-1 Human fly adsorption: 1l (q/f carrier) Example 1 0.93 0.87 Comparative example】 - Comparative example 2 5.0 0
Claims (1)
”以下、室温におけるヤング率が１ ｘ １０１１ｄ
ｙｎｅｓｃ＊”−”以上で、かつ構成素材の吸水率が２
０−以下の多孔性担体上に生理活性物質を固定化し、し
かる後に湿熱滅菌することを特徴とする生理活性物質固
定化担体の製造方法。 ２、多孔性担体の構成素材が金属、ガラス、アルミナ、
シリカ、あるいは湿熱滅菌温度以上のガラス転移温度（
Ｔｇ ）を持つ有機体、あるいはこれらの複合体でるる
特許請求の範囲第１項記載の生理活性物質固定化担体の
製造方法。 ３、多孔性担体が、平均細孔直径１０００λ以上で、か
つ細孔容積が０．３ ｍ ｇ−を以上の多孔性担体であ
る特許請求の範囲第１項あるいは第２項記載の生理活性
物質固定化担体の製造方法。 ４、 多孔性担体表面に化学結合可能な活性基を１ ｘ
１０−”ｍｏｌｅｍ−” 以上Ｏ濃度テ有Ｌ、当ｍ活
性基を介して生理活性物質を特徴とする特許請求の範囲
第１項〜第３項記載の生理活性物質固定化担体の製造方
法。 ５、化学結合可能な活性基がアミノ基、カルボキシル基
、アルデヒド基、エポキシ基よシなる群から１つ以上選
択された特許請求の範囲第４項記載の生理活性物質固定
化担体の製造方法。[Claims] 1. The coefficient of linear expansion at room temperature is 3 x 10-'deg.
``Hereinafter, Young's modulus at room temperature is 1 x 1011d
ynesc*”-” or more, and the water absorption rate of the constituent material is 2
1. A method for producing a physiologically active substance-immobilized carrier, which comprises immobilizing a physiologically active substance on a 0- or less porous carrier and then sterilizing it with moist heat. 2. The constituent material of the porous carrier is metal, glass, alumina,
silica or glass transition temperature higher than the moist heat sterilization temperature (
The method for producing a physiologically active substance-immobilized carrier according to claim 1, which is made of an organism having Tg ) or a complex thereof. 3. The physiologically active substance according to claim 1 or 2, wherein the porous carrier has an average pore diameter of 1000λ or more and a pore volume of 0.3 mg or more. Method for producing immobilization carrier. 4. 1 x active group capable of chemical bonding on the surface of the porous carrier
4. A method for producing a physiologically active substance-immobilized carrier according to claims 1 to 3, characterized in that the physiologically active substance is transferred via an active group with an O concentration of 10-"molem-" or more. 5. The method for producing a physiologically active substance-immobilized carrier according to claim 4, wherein the active group capable of chemical bonding is one or more selected from the group consisting of an amino group, a carboxyl group, an aldehyde group, and an epoxy group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5690983A JPS59184134A (en) | 1983-03-31 | 1983-03-31 | Production of carrier for immobilizing physiologically active substance |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5690983A JPS59184134A (en) | 1983-03-31 | 1983-03-31 | Production of carrier for immobilizing physiologically active substance |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59184134A true JPS59184134A (en) | 1984-10-19 |
| JPH0549651B2 JPH0549651B2 (en) | 1993-07-26 |
Family
ID=13040580
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5690983A Granted JPS59184134A (en) | 1983-03-31 | 1983-03-31 | Production of carrier for immobilizing physiologically active substance |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59184134A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10194867D2 (en) | 2000-11-08 | 2003-11-20 | Willytec Gmbh Technologiezentr | (Dental) surface detection and generation |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56147710A (en) * | 1980-04-16 | 1981-11-16 | Kuraray Co Ltd | Immunoglobulin adsorbent |
| JPS56147711A (en) * | 1980-04-16 | 1981-11-16 | Kuraray Co Ltd | Albumin adsorbent |
-
1983
- 1983-03-31 JP JP5690983A patent/JPS59184134A/en active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56147710A (en) * | 1980-04-16 | 1981-11-16 | Kuraray Co Ltd | Immunoglobulin adsorbent |
| JPS56147711A (en) * | 1980-04-16 | 1981-11-16 | Kuraray Co Ltd | Albumin adsorbent |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0549651B2 (en) | 1993-07-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0054799B1 (en) | A dried, sterilized, gamma-globulin-fixed column and a process for preparing the same | |
| US5283034A (en) | Stabilization of sterilized surfaces for research and medical use | |
| JP2016120333A (en) | Improved separation | |
| JPH06502156A (en) | Solid surfaces coated with a hydrophilic outer layer containing covalently bound biopolymers, methods for producing such surfaces, and conjugates therefor | |
| JP2006300965A (en) | Stable avidin composition and method of use | |
| US6686457B1 (en) | Material | |
| JPS6159175B2 (en) | ||
| JPH0144725B2 (en) | ||
| US4839290A (en) | Process for producing cytotoxic T-cells and compositions produced by said process | |
| JP2618497B2 (en) | Tumor-damaging cell inducer and tumor-damaging cell induction device | |
| US5219926A (en) | Method of covalently bonding biopolymer to a solid hydrophilic organic polymer | |
| JPH0256104B2 (en) | ||
| JP2000217575A (en) | Adsorbent of physiologically active substance, human blood cell differentiation cell and human cell | |
| JPS59184134A (en) | Production of carrier for immobilizing physiologically active substance | |
| JPH0135670B2 (en) | ||
| JPH0622633B2 (en) | Adsorbent and removal device using the same | |
| AU2008201015B2 (en) | Improved separation | |
| JP3357139B2 (en) | Adsorbent for anti-deoxyribonucleic acid antibody | |
| EP0506818B1 (en) | Method of covalently bonding proteins to hydrophilic surfaces | |
| Hoffman | Applications of synthetic polymeric biomaterials in medicine and biotechnology | |
| JP3620863B2 (en) | Interleukin 1 production induction method | |
| JPH0523395A (en) | Blood purifying adsorbent | |
| JPH1045601A (en) | Antiviral material | |
| JP2726662B2 (en) | Adsorbent and removal device using the same | |
| JPS6412280B2 (en) |