JP2002102338A - Interferon gamma removing material, interferon gamma removing column and interferon gamma removing method - Google Patents
Interferon gamma removing material, interferon gamma removing column and interferon gamma removing methodInfo
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- JP2002102338A JP2002102338A JP2000293656A JP2000293656A JP2002102338A JP 2002102338 A JP2002102338 A JP 2002102338A JP 2000293656 A JP2000293656 A JP 2000293656A JP 2000293656 A JP2000293656 A JP 2000293656A JP 2002102338 A JP2002102338 A JP 2002102338A
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Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、インターフェロン
ガンマ除去材料およびそれを用いたインターフェロンガ
ンマ除去カラムに関する。特にヒト血液中のインターフ
ェロンガンマを除去する事により、炎症などの病態を改
善させる用途に好適に用いられる。The present invention relates to a material for removing interferon gamma and a column for removing interferon gamma using the same. In particular, it is suitably used for applications that improve pathological conditions such as inflammation by removing interferon gamma from human blood.
【０００２】[0002]
【従来の技術】インターフェロン（ＩＦＮ）は抗ウィル
ス作用のあるサイトカインであり、α、β、γの３型が
ある。サイトカインとは、生体のさまざまな高次機能を
維持する上で重要な細胞間情報伝達物質（糖タンパク）
である。サイトカインは、免疫系、造血系、内分泌系、
神経系などで作用する事が知られているが、それぞれの
サイトカインは多機能であると共に、サイトカイン同士
で機能の重複が見られ、複雑なネットワークを形成して
いる。このうちインターフェロンについては、多くの免
疫反応を制御することが明らかとなった。2. Description of the Related Art Interferon (IFN) is a cytokine having an antiviral effect, and has three types, α, β and γ. Cytokines are intercellular messengers (glycoproteins) that are important in maintaining various higher-order functions of the body
It is. Cytokines are immune, hematopoietic, endocrine,
It is known that they act on the nervous system and the like, but each cytokine is multifunctional, and the cytokines have overlapping functions, forming a complex network. Of these, interferon was found to control many immune responses.
【０００３】炎症とは、さまざまな侵襲に対する基本的
な生体防御反応である。その引き金となるのは炎症時に
誘導される各種サイトカインである。インターロイキン
１や腫瘍壊死因子、インターフェロンガンマ（以下ＩＦ
Ｎ−γと略す）などは炎症性サイトカインと呼ばれてい
る。これらの炎症性サイトカインが脳内視床下部の体温
中枢に作用して、炎症局所での発熱を誘導し、骨髄では
貯留白血球を動員し、骨髄系細胞の増殖を促進する。さ
らに、肝臓に作用して急性期反応タンパク質の産生を誘
導する。この様に、炎症性サイトカインをきっかけとし
て、種々の反応がはじまり、炎症局所への白血球の浸潤
が起こる。組織へ浸潤した白血球はさまざまなプロテア
ーゼ、活性酸素、アラキドン酸代謝物、一酸化窒素など
を産生することによって、組織破壊を引き起こす。こう
して局所での炎症は全身の反応へと広がっていく。この
ことからも、ＩＦＮ−γなどの炎症性サイトカインが、
炎症反応に重大な影響を与えているといえる。具体的に
は、感染した細菌の毒素による敗血症などの全身性炎症
においても、ＩＦＮ−γなどの炎症性サイトカインが症
状の増悪の一因となっている。[0003] Inflammation is a basic host defense response to various invasions. The trigger is various cytokines induced during inflammation. Interleukin 1, tumor necrosis factor, interferon gamma (IF
N-γ) is called an inflammatory cytokine. These inflammatory cytokines act on the body temperature center in the hypothalamus of the brain to induce fever in local areas of inflammation, recruit stored leukocytes in the bone marrow, and promote the proliferation of myeloid cells. In addition, it acts on the liver to induce the production of acute phase response proteins. In this manner, various reactions start with the trigger of the inflammatory cytokine, and infiltration of leukocytes into the inflamed area occurs. Leukocytes infiltrating tissues cause tissue destruction by producing various proteases, active oxygen, arachidonic acid metabolites, nitric oxide and the like. Thus, local inflammation spreads to a systemic response. From this, inflammatory cytokines, such as IFN-γ,
It can be said that it has a significant effect on the inflammatory response. Specifically, in systemic inflammation such as sepsis due to toxins of infected bacteria, inflammatory cytokines such as IFN-γ contribute to exacerbation of symptoms.
【０００４】炎症に深く関わっていると考えられている
リンパ球の一種であるヘルパーＴ細胞は大きくＴｈ１、
Ｔｈ２と呼ばれる２つのグループに分化することがわか
っている。この２つの細胞集団のアンバランスが、さま
ざまな免疫関連疾患の病態に関わるものと考えられてい
る。単純に言えば、Ｔｈ１細胞は細胞障害性細胞であ
り、Ｔｈ２細胞は抗体産生を誘導する細胞であると言え
る。慢性の炎症性疾患である慢性関節リウマチや、Ｉ型
（インスリン依存性）糖尿病などの自己免疫疾患ではＩ
ＦＮ−γなどを産生するＴｈ１に、気管支喘息やアトピ
ー性皮膚炎などのアレルギー性疾患ではインターロイキ
ン４（以下ＩＬ−４と略す）などを産生するＴｈ２に偏
っているといわれている。また、ＩＦＮ−γはＴｈ１へ
の分化を促進してＴｈ２への分化を抑制し、ＩＬ−４は
Ｔｈ２への分化を促進してＴｈ１への分化を抑制すると
いう作用があり、２者は相互抑制的な関係にある。これ
らのことから、ＩＦＮ−γやＩＬ−４などは、免疫応答
をその物質量で制御するだけでなく、免疫応答様式とい
う質的な制御にも関与していると考えられている。この
ことからも、自己免疫疾患における炎症反応において、
ＩＦＮ−γが重要な役割を果たしていると言える。[0004] Helper T cells, which are a type of lymphocyte thought to be deeply involved in inflammation, are largely Th1,
It has been found to differentiate into two groups called Th2. It is thought that the imbalance between these two cell populations is involved in the pathology of various immune-related diseases. Simply stated, Th1 cells are cytotoxic cells, and Th2 cells are cells that induce antibody production. In autoimmune diseases such as rheumatoid arthritis, which is a chronic inflammatory disease, and type I (insulin-dependent) diabetes,
It is said that Th1 that produces FN-γ or the like is biased toward Th2 that produces interleukin 4 (hereinafter abbreviated as IL-4) in allergic diseases such as bronchial asthma and atopic dermatitis. IFN-γ promotes Th1 differentiation and suppresses Th2 differentiation, and IL-4 promotes Th2 differentiation and suppresses Th1 differentiation. There is an inhibitory relationship. From these facts, it is considered that IFN-γ and IL-4 are involved not only in controlling the immune response by the amount of the substance but also in qualitative control of the immune response mode. From this, in the inflammatory response in autoimmune diseases,
It can be said that IFN-γ plays an important role.
【０００５】サイトカインを吸着する材料としては、特
開平１０−１４７５１８号公報に報告されているが、血
漿中のＩＦＮ−γを高効率で除去できる材料は報告され
ていない。As a material for adsorbing cytokines, Japanese Patent Application Laid-Open No. H10-147518 reports, but no material capable of removing IFN-γ in plasma with high efficiency has been reported.
【０００６】[0006]
【発明が解決しようとする課題】本発明はかかる炎症を
引き起こすと言われている炎症性サイトカインの１つで
あるＩＦＮ−γを除去するための材料、およびそれを用
いた除去カラムを提供することを目的とする。The object of the present invention is to provide a material for removing IFN-γ, one of the inflammatory cytokines which are said to cause such inflammation, and a removal column using the same. With the goal.
【０００７】[0007]
【課題を解決するための手段】すなわち本発明は、生理
活性物質が水不溶性担体に固定化されてなるＩＦＮ−γ
除去材料である。That is, the present invention provides an IFN-γ comprising a physiologically active substance immobilized on a water-insoluble carrier.
It is a removal material.
【０００８】また本発明は、上記の材料を内蔵してなる
ＩＦＮ−γ除去カラムである。[0008] The present invention is also an IFN-γ removal column incorporating the above-mentioned material.
【０００９】また本発明は、上記のカラムにＩＦＮ−γ
を含む液体を通過させる、ＩＦＮ−γ除去方法である。[0009] The present invention also relates to the present invention, wherein IFN-γ
This is a method for removing IFN-γ in which a liquid containing is passed.
【００１０】[0010]
【発明の実施の形態】本発明においては、ＩＦＮ−γ除
去材料を提供することができる。本発明のＩＦＮ−γ除
去材料は、生理活性物質が水不溶性担体に固定化されて
なることが重要である。BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, a material for removing IFN-γ can be provided. It is important that the material for removing IFN-γ of the present invention has a physiologically active substance immobilized on a water-insoluble carrier.
【００１１】本発明でいう生理活性物質とは、生物体内
に含まれる物質で、その生理現象を促進あるいは抑制す
る機能を持ち、また、他の生物体の生命現象あるいは生
物体相互の係わり合いに影響を及ぼす物質の総称であ
る。具体的には、抗生物質やホルモン、ポリペプチド、
多糖類、核酸等をいう。抗生物質としては、ポリミキシ
ン、バンコマイシン、アクチノマイシン、バイオマイシ
ン等が上げられ、ポリペプチドとしては、アルブミン、
プロテインＡなどが上げられる。中でも該ポリミキシン
とはBacillus Polymixaにより産生される抗生物質であ
り、ポリミキシンＡ、ポリミキシンＢ、ポリミキシン
Ｄ、ポリミキシンＥ等のタイプがあり、グラム陰性菌に
対して抗菌作用を有する。The physiologically active substance referred to in the present invention is a substance contained in a living organism, which has a function of promoting or suppressing its physiological phenomena. It is a general term for substances that have an effect. Specifically, antibiotics, hormones, polypeptides,
Refers to polysaccharides, nucleic acids and the like. Antibiotics include polymyxin, vancomycin, actinomycin, biomycin, etc., and polypeptides include albumin,
Such as protein A. Among them, the polymyxin is an antibiotic produced by Bacillus Polymixa, and is of a type such as polymyxin A, polymyxin B, polymyxin D, polymyxin E, and has an antibacterial activity against Gram-negative bacteria.
【００１２】本発明に用いられる不溶性担体の材料とし
ては、ポリスチレン、ポリプロピレン、ポリアミド、ポ
リイミド、ポリ（芳香族ビニル化合物）、ポリエステ
ル、ポリメチルメタクリレート、ポリスルホン、ポリエ
チレン、ポリビニルアルコール、ポリテトラフルオロエ
チレンなどの合成高分子や、セルロース、コラーゲン、
キチン、キトサン、デキストランおよびそれらの誘導体
を含む天然高分子、などが好適に用いられる。さらに、
金属、セラミックス、ガラスなどの無機材料を適当な高
分子で被覆したり、表面を直接修飾したものも好適に用
いられる。Examples of the material of the insoluble carrier used in the present invention include polystyrene, polypropylene, polyamide, polyimide, poly (aromatic vinyl compound), polyester, polymethyl methacrylate, polysulfone, polyethylene, polyvinyl alcohol and polytetrafluoroethylene. Synthetic polymers, cellulose, collagen,
Natural polymers including chitin, chitosan, dextran and their derivatives are preferably used. further,
A material obtained by coating an inorganic material such as metal, ceramics, or glass with a suitable polymer or directly modifying the surface is also preferably used.
【００１３】特に、ポリスチレン、架橋ポリスチレン、
アクリル酸・アクリロニトリル共重合体、カルボキシル
基を有するポリビニルアルコールから選ばれるものを含
むのが、官能基の導入が特に容易な点で好ましい。In particular, polystyrene, cross-linked polystyrene,
It is preferable to include those selected from an acrylic acid / acrylonitrile copolymer and a polyvinyl alcohol having a carboxyl group, since the introduction of a functional group is particularly easy.
【００１４】本発明の材料の形状としては、繊維状、ビ
ーズ状、平膜状、紛状などを用いることができるが、特
に血球と血漿とを分離せずにカラムに循環する全血体外
循環にも適している点で、繊維状やビーズ状のものが好
ましく用いられる。更に繊維状としては、中空糸状や海
島状が好ましい。海島状は海成分として上記のような官
能基の導入が容易なものを用い、島成分として加工性と
耐久性に優れたものを用いて補強することができる。例
えば、海成分としてはポリスチレン、島成分としてはポ
リプロピレン等を用いることができる。The material of the present invention may be in the form of fibers, beads, flat membranes, powders, or the like. In particular, whole blood extracorporeal circulation which circulates through a column without separating blood cells and plasma. Fibers and beads are preferably used in that they are also suitable. Further, as the fibrous shape, a hollow fiber shape or a sea-island shape is preferable. The sea-island shape can be reinforced using a sea component into which a functional group as described above can be easily introduced and using an island component having excellent workability and durability. For example, polystyrene can be used as the sea component, and polypropylene or the like can be used as the island component.
【００１５】吸着率を上げるには、多孔性等、接触面積
の大きいものが好ましい。更に、体外循環に用いるよう
なカラムに充填する場合には、圧損を抑えるよう考慮す
ることも好ましい。例えばビーズとしては、粒径が５０
〜１０００μｍのものが好ましく、２００〜７００μｍ
のものがさらに好ましい。また繊維状としては、体外循
環に用いることを想定した場合、０．１〜１００ｍ2／
ｇの表面積のものが好ましい。表面積はベット法によっ
て測定されるものとする。In order to increase the adsorption rate, a material having a large contact area such as porosity is preferable. Furthermore, when packing in a column used for extracorporeal circulation, it is also preferable to consider to suppress pressure loss. For example, as beads, the particle size is 50
~ 1000 μm is preferable, and 200 to 700 μm
Are more preferred. Moreover, as a fibrous form, when it is assumed that it is used for extracorporeal circulation, 0.1 to 100 m 2 /
g are preferred. The surface area shall be measured by the bed method.
【００１６】ＩＦＮ−γの吸着率は、繊維状のものであ
れば２５ｍｇ、ビーズ状のもであれば２００μｌに対し
て、２５０ｐｇ／ｍｌの濃度のＩＦＮ−γ添加正常ヒト
血清１ｍｌを３７℃で２時間反応させたときの吸着率で
示した場合、３０％以上、好ましくは５０％以上である
ことが望ましい。The adsorption rate of IFN-γ is 25 mg for a fibrous substance and 200 μl for a bead, and 1 ml of IFN-γ-added normal human serum at a concentration of 250 pg / ml is added at 37 ° C. In the case of the adsorption rate when reacted for 2 hours, it is desirably 30% or more, preferably 50% or more.
【００１７】上記のようなＩＦＮ−γ除去材料を容器に
内蔵させ、ＩＦＮ−γ除去カラムとすることができる。
その態様の１例としては、本発明の繊維状のＩＦＮ−γ
除去材料を布状とし、中空で軸表面に孔が形成された中
心軸に巻き付けてカラムに詰め、中心軸内部にＩＦＮ−
γを含有する液体を流し、中心軸に形成された孔から処
理液を外部に流出するような構造のものが、効率よくＩ
ＦＮ−γを吸着・除去できる点で好ましい。The IFN-γ removal material described above can be incorporated in a container to form an IFN-γ removal column.
One example of such an embodiment is the fibrous IFN-γ of the present invention.
The material to be removed was made into a cloth, wrapped around a hollow central shaft having holes formed in the shaft surface, packed into a column, and IFN-
A structure in which a liquid containing γ is made to flow and the processing liquid flows out from a hole formed in the central axis to the outside is efficiently used.
This is preferable because FN-γ can be adsorbed and removed.
【００１８】本発明の除去カラムに、ＩＦＮ−γを含む
血液や血漿等の液体を体外循環等で通過させることによ
り、ＩＦＮ−γを除去することができる。IFN-γ can be removed by passing a liquid such as blood or plasma containing IFN-γ through the removal column of the present invention by extracorporeal circulation or the like.
【００１９】本発明により、例えば炎症を引き起こして
いる患者の体液からＩＦＮ−γを人為的に除去すること
ができ、炎症性疾患治療などの用途に好適に用いること
ができる。According to the present invention, for example, IFN-γ can be artificially removed from a body fluid of a patient having inflammation, and the IFN-γ can be suitably used for applications such as treatment of inflammatory diseases.
【００２０】[0020]
【実施例】以下に実施例を用いて詳細な検討を加える
が、発明の内容が実施例に限定されるものではない。The present invention will be described in detail below with reference to examples, but the present invention is not limited to the examples.
【００２１】（ＩＦＮ−γ吸着率の測定法）繊維状のも
のであれば２５ｍｇ、ビーズ状のもであれば２００μｌ
を用い、ＩＦＮ−γ２５０ｐｇ／ｍｌを添加した正常ヒ
ト血清１ｍｌに３７℃で２時間浸漬させ、吸着除去前の
血清中と吸着除去後の血清中とのＩＦＮ−γを酵素免疫
測定法で測定した。吸着除去前の血清中のＩＦＮ−γ濃
度をＡ、吸着除去後の血清中のＩＦＮ−γ濃度をＢとし
て、（Ａ−Ｂ／Ａ）Ｘ１００でＩＦＮ−γ吸着率（％）
を算出した。(Measurement method of IFN-γ adsorption rate) 25 mg for fibrous, 200 μl for bead
And immersed in 1 ml of normal human serum supplemented with 250 pg / ml of IFN-γ at 37 ° C. for 2 hours, and measured the IFN-γ in the serum before and after the adsorption removal by enzyme immunoassay. . Assuming that IFN-γ concentration in serum before adsorption and removal is A and IFN-γ concentration in serum after adsorption and removal is B, IFN-γ adsorption rate (%) is (AB / A) × 100.
Was calculated.
【００２２】（実施例１）ポリプロピレン（三井“ノー
ブレン”Ｊ３ＨＧ）５０重量部を島成分とし、ポリスチ
レン（“スタイロン”６６６）４６重量部、ポリプロピ
レン（住友“ノーブレン”ＷＦ−７２７−Ｆ）４重量部
の混合物を海成分とする海島型複合繊維（島数１６、単
糸繊度２．６デニール、引張強度２．９ｇ／ｄ、伸度５
０％、フィラメント数４２）５０ｇを、Ｎ−メチロ−ル
−α−クロルアセトアミド９０．５g、ニトロベンゼン
６００g、９８％硫酸６００ｇおよびパラホルムアルデ
ヒド１．２９gからなる混合溶液中に浸し、１０℃で２
時間反応させた。繊維を反応液から取り出し、１０５０
gのニトロベンゼンで洗浄した後、８５０ｍｌの水で洗
浄し、次に２４％ＮａＯＨ溶液２５ｍｌで中和を行っ
た。この繊維を１０００ｍｌのメタノールで洗浄し、最
後に温水洗浄を行った。Example 1 50 parts by weight of polypropylene (Mitsui "Noblen" J3HG) as an island component, 46 parts by weight of polystyrene ("Stylon" 666), 4 parts by weight of polypropylene (Sumitomo "Noblen" WF-727-F) Sea-island type composite fiber (island number 16, single yarn fineness 2.6 denier, tensile strength 2.9 g / d, elongation 5)
0%, number of filaments 42) 50 g was immersed in a mixed solution consisting of 90.5 g of N-methylol-α-chloroacetamide, 600 g of nitrobenzene, 600 g of 98% sulfuric acid and 1.29 g of paraformaldehyde, and 10 ° C.
Allowed to react for hours. The fiber is removed from the reaction solution and 1050
After washing with g of nitrobenzene, it was washed with 850 ml of water and then neutralized with 25 ml of a 24% NaOH solution. The fibers were washed with 1000 ml of methanol and finally washed with warm water.
【００２３】上記で得られたクロルアセトアミドメチル
化繊維に、ポリミキシンＢ（ＤＵＭＥＸ社製）１．０２
ｇを６５０mlの水にとかしたものと０．１Ｎ ＮａＯＨ
２５ｍｌを加え、１時間振とうし固定化反応を行った。
反応した繊維は０．０７７Ｎ−塩酸６５０ｍｌで３回洗
浄した後に、水６５０ｍｌで３回洗浄し、ポリミキシン
固定化繊維を得た。ポリミキシン固定化量はアミノ酸分
析法から６ｍｇ／ｇであった。[0023] Polymyxin B (manufactured by DUMEX) 1.02 was added to the chloracetamidomethylated fiber obtained above.
g in 650 ml of water and 0.1 N NaOH
25 ml was added, and the mixture was shaken for 1 hour to perform an immobilization reaction.
The reacted fiber was washed three times with 650 ml of 0.077N hydrochloric acid and then three times with 650 ml of water to obtain a polymyxin-immobilized fiber. The amount of immobilized polymyxin was 6 mg / g by amino acid analysis.
【００２４】上記で得られたポリミキシン固定化繊維を
蒸気滅菌し２５ｍｇにカットし、上記ＩＦＮ−γ吸着率
の測定法に従い、ＩＦＮ−γの吸着率を算出した。その
結果、ＩＦＮ−γの吸着率は８２．７％で、生理活性物
質を固定化した担体によって、血清中のＩＦＮ−γがよ
く吸着除去された。The polymyxin-immobilized fiber obtained above was steam sterilized, cut into 25 mg, and the IFN-γ adsorption rate was calculated according to the IFN-γ adsorption rate measurement method described above. As a result, the IFN-γ adsorption rate was 82.7%, and IFN-γ in serum was well adsorbed and removed by the carrier on which the physiologically active substance was immobilized.
【００２５】[0025]
【発明の効果】本発明により、ＩＦＮ−γ除去材料を提
供することができた。According to the present invention, a material for removing IFN-γ can be provided.
───────────────────────────────────────────────────── フロントページの続き Ｆターム(参考） 4C077 AA11 BB03 KK11 MM04 MM06 MM07 NN18 PP02 PP05 PP08 PP09 PP10 PP12 PP13 PP15 PP21 PP24 PP29 4D017 AA11 BA07 CA14 CB01 CB03 DA01 EA10 EB03 EB07 4G066 AC01B AC03B AC06B AC12C AC14C AC17C BA16 BA36 CA20 CA54 DA12 EA01 ──────────────────────────────────────────────────続 き Continued on the front page F-term (reference) 4C077 AA11 BB03 KK11 MM04 MM06 MM07 NN18 PP02 PP05 PP08 PP09 PP10 PP12 PP13 PP15 PP21 PP24 PP29 4D017 AA11 BA07 CA14 CB01 CB03 DA01 EA10 EB03 EB07 4G066 AC01B AC12 AC06 CA20 CA54 DA12 EA01
Claims (12)
てなるインターフェロンガンマ除去材料。1. An interferon gamma-removing material comprising a physiologically active substance immobilized on a water-insoluble carrier.
載のインターフェロンガンマ除去材料。2. The material for removing interferon gamma according to claim 1, wherein the physiologically active substance comprises an antibiotic.
載のインターフェロンガンマ除去材料。3. The material for removing interferon gamma according to claim 1, wherein the physiologically active substance comprises a peptide.
項１〜３いずれか記載のインターフェロンガンマ除去材
料。4. The material for removing interferon gamma according to claim 1, wherein the water-insoluble carrier has a fibrous form.
項１〜３いずれか記載のインターフェロンガンマ除去材
料。5. The material for removing interferon gamma according to claim 1, wherein the water-insoluble carrier has a bead form.
スチレン、アクリル酸・アクリロニトリル共重合体及び
カルボキシル基を有するポリビニルアルコールから選ば
れるものを含む請求項４または５記載のインターフェロ
ンガンマ除去材料。6. The interferon gamma-removing material according to claim 4, wherein the water-insoluble carrier comprises a material selected from polystyrene, cross-linked polystyrene, acrylic acid / acrylonitrile copolymer, and polyvinyl alcohol having a carboxyl group.
蔵してなるインターフェロンガンマ除去カラム。7. An interferon gamma removal column comprising the material according to claim 1 incorporated therein.
ガンマを含む液体を通過させるインターフェロンガンマ
除去方法。8. A method for removing interferon gamma by passing a liquid containing interferon gamma through the column according to claim 7.
のインターフェロンガンマ除去方法。9. The method for removing interferon gamma according to claim 9, wherein the liquid is blood or plasma.
疾患治療用のインターフェロンガンマ除去材料。10. A material for removing interferon gamma according to claim 1, which is used for treating inflammatory diseases.
ターフェロンガンマ除去カラム。11. The column according to claim 7, which is used for treating inflammatory diseases.
ターフェロンガンマ除去方法。12. The method for removing interferon gamma according to claim 8, for improving inflammation.
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| JP2007057518A (en) * | 2005-07-27 | 2007-03-08 | Mitsubishi Chemicals Corp | Biomaterial structure, its manufacturing method, biomaterial carrier, object matter purification method, container for affinity chromatography, chip for separation, object matter analysis method, separation apparatus for object substance analysis, and sensor chip |
| JP2007101520A (en) * | 2005-09-09 | 2007-04-19 | Mitsubishi Chemicals Corp | Biological material complex, biological material complex carrier, method for purifying object material, container for affinity chromatography, chip for separation, separation apparatus and method for analyzing object material, and sensor chip |
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