公开(公告)号：US5616693A

公开(公告)日：1997-04-01

申请号：US673064

申请日：1996-07-01

申请人： Duk S. Hwang ,  Evelyn Nario ,  Mark Lepe ,  Lyndon Luz ,  Hirokazu Ito ,  Kazuo Takechi

发明人： Duk S. Hwang ,  Evelyn Nario ,  Mark Lepe ,  Lyndon Luz ,  Hirokazu Ito ,  Kazuo Takechi

IPC分类号： C12N9/64 ,  C07K1/14 ,  C07K14/775 ,  C07K14/81

CPC分类号： C07K14/775 ,  C07K14/8125 ,  Y10S530/811 ,  Y10S530/812

摘要： The present invention is directed to a process for purifying alpha-1-PI. The process comprises providing an impure protein fraction which comprises alpha-1-PI. The impure protein fraction is suspended in an aqueous solution at pH 6. Insoluble proteins are recovered and resuspended in aqueous solution at pH 8.5. PEG is added to precipitate .alpha.-2 proteins. To the PEG supernatant precipitation, which comprises alpha-1-PI, is added ZnCl.sub.2 to precipitate crude alpha-1-PI. The crude alpha-1-PI is resolubilized and applied to an anion-exchange medium. A fraction comprising alpha-1-PI is recovered from the anion-exchange medium. Alpha-1-PI purified by the process has a specific activity about 1.0 units/OD.sub.280.

摘要翻译： 本发明涉及纯化α-1-PI的方法。 该方法包括提供包含α-1-PI的不纯蛋白质级分。 将不纯的蛋白质级分悬浮在pH6的水溶液中。回收不溶性蛋白质并将其重悬于pH8.5的水溶液中。 添加PEG以沉淀α-2蛋白。 向包含α-1-PI的PEG上清液中加入ZnCl 2以沉淀粗α-1-PI。 将粗α-1-PI重新溶解并施用于阴离子交换介质。 从阴离子交换介质中回收包含α-1-PI的级分。 通过该方法纯化的α-1-PI具有约1.0单位/ OD280的比活度。

公开(公告)号：US5132406A

公开(公告)日：1992-07-21

申请号：US348139

申请日：1989-05-05

申请人： Yahiro Uemura ,  Katuhiro Uriyu ,  Kazuo Takechi ,  Yutaka Hirao ,  Tadakazu Suyama

发明人： Yahiro Uemura ,  Katuhiro Uriyu ,  Kazuo Takechi ,  Yutaka Hirao ,  Tadakazu Suyama

IPC分类号： A61K39/395 ,  A61K38/00 ,  A61L2/00 ,  C07K16/00

CPC分类号： C07K16/00 ,  A61L2/0023 ,  A61K38/00

摘要： A method of producing immunoglobulin preparations for intravenous injection which starts with an immunoblobulin-containing fraction and comprises the treatment steps of:(a) treating said fraction with 4-10 weight/volume percent of polyethylene glycol having a molecular weight of 1,000-10,000 under conditions of pH 4-6, ion strength 0.0001-0.1M and temperature 0.degree.-4.degree. C. and recovering the supernatant,(b) treating the supernatant obtained in step (a) with 10-15 weight/volume percent of polyethylene glycol having a molecular weight of 1,000-10,000 under conditions of pH 6-9, ion strength 0.0001-0.1M and temperature 0.degree.-4.degree. C. and recovering the resulting precipitate, and(c) heat-treating, in any desired step, said immunoglobulin in the presence of a stabilizer under conditions sufficient to inactivate contaminant viruses.The preparations obtained according to the invention retain immunoglobulins without substantial inactivation thereof, and are substantially free of such contaminants as anti-human blood group substance antibodies. With contaminant viruses inactivated as a result of the heat treatment, said preparations have good solubility and are sufficiently low in anticomplement activity.

摘要翻译： 一种生产用于静脉注射的免疫球蛋白制剂的方法，其起始于含免疫球蛋白的级分，并且包括以下处理步骤：（a）用4-10重量/体积％的分子量为1,000-10,000的聚乙二醇处理所述级分， 条件pH 4-6，离子强度0.0001-0.1M，温度0℃-4℃，回收上清液，（b）用10-15重量/体积％聚乙二醇处理步骤（a）中得到的上清液 在pH 6-9，离子强度为0.0001-0.1M，温度为0〜-4℃的条件下分子量为1,000〜10,000，回收所得沉淀物，（c）在任何所需步骤中热处理， 所述免疫球蛋白在足以灭活污染性病毒的条件下在稳定剂存在下进行。 根据本发明获得的制剂保留免疫球蛋白而基本上不灭活，并且基本上不含抗人血型物质抗体等污染物。 随着由于热处理而灭活的污染物病毒，所述制剂具有良好的溶解性并且抗补体活性足够低。

公开(公告)号：US4740498A

公开(公告)日：1988-04-26

申请号：US790668

申请日：1985-10-23

申请人： Yutaka Hirao ,  Takao Ohmura ,  Kazuo Takechi ,  Tsunetaka Nakajima ,  Masayuki Nishida

发明人： Yutaka Hirao ,  Takao Ohmura ,  Kazuo Takechi ,  Tsunetaka Nakajima ,  Masayuki Nishida

IPC分类号： A61K38/16 ,  A61K9/00 ,  A61K38/39 ,  A61K47/10 ,  A61K47/26 ,  A61K47/42 ,  A61K37/04 ,  A61K35/14 ,  A61K37/02

CPC分类号： A61K47/42 ,  A61K38/39 ,  A61K47/10 ,  A61K47/26 ,  A61K9/0048

摘要： A fibronectin preparation in the form of an aqueous solution at least upon use is disclosed. The preparation contains at least one member selected from the group consisting of disaccharides, albumin and nonionic surface active agents as a stabilizer. The preparation has improved water-solubility when in use and high stability in an aqueous solution.

摘要翻译： 公开了至少使用水溶液形式的纤连蛋白制剂。 该制剂含有选自二糖，白蛋白和非离子表面活性剂作为稳定剂的至少一种。 该制剂在使用时具有改善的水溶性和在水溶液中的高稳定性。

公开(公告)号：US06504012B2

公开(公告)日：2003-01-07

申请号：US09861713

申请日：2001-05-22

申请人： Raja R. Mamidi ,  Andranik Bagdasarian ,  Gorgonio Canaveral ,  Kazuo Takechi

发明人： Raja R. Mamidi ,  Andranik Bagdasarian ,  Gorgonio Canaveral ,  Kazuo Takechi

IPC分类号： A61K3516

CPC分类号： C07K16/065

摘要： A process for producing an intravenously-administrable gamma globulin solution substantially free of contaminating viruses by fractionating an impure gamma globulin solution and then treating the purified gamma globulin, in any order, with a solvent-detergent for viral inactivation and a heat treating for viral inactivation. Thereafter, denatured impurities, residual solvent and aggregate generated by the heat treatment are removed from the gamma globulin.

摘要翻译： 通过分级分离不纯的γ球蛋白溶液，然后以任何顺序用溶剂洗涤剂，用于病毒灭活和用于病毒灭活的热处理来生产静脉内施用的γ球蛋白溶液基本上不含污染病毒的方法 。 此后，从γ-球蛋白中除去变性杂质，残留溶剂和通过热处理产生的骨料。

公开(公告)号：US06441144B1

公开(公告)日：2002-08-27

申请号：US09316117

申请日：1999-05-20

申请人： Raja R. Mamidi ,  Andranik Bagdasarian ,  Gorgonio Canaveral ,  Kazuo Takechi

发明人： Raja R. Mamidi ,  Andranik Bagdasarian ,  Gorgonio Canaveral ,  Kazuo Takechi

IPC分类号： C07K1606

CPC分类号： C07K16/065

摘要： A process for producing an intravenously-administrable gamma globulin solution substantially free of contaminating viruses by fractionating an impure gamma globulin solution and then treating the purified gamma globulin, with a solvent-detergent for viral inactivation and a heat treating for viral inactivation. Thereafter, denatured impurities, residual solvent and aggregate generated by the heat treatment are removed from the gamma globulin.

摘要翻译： 用于通过分级不纯的γ球蛋白溶液然后用用于病毒灭活的溶剂洗涤剂和用于病毒灭活的热处理纯化的γ球蛋白来生产基本上不含污染病毒的静脉内施用的γ球蛋白溶液的方法。 此后，从γ-球蛋白中除去变性杂质，残留溶剂和通过热处理产生的骨料。

公开(公告)号：US5981715A

公开(公告)日：1999-11-09

申请号：US829223

申请日：1997-03-31

申请人： Duk Sung Hwang ,  Evelyn Nario ,  Mark Lepe ,  Lyndon Luz ,  Hirokazu Ito ,  Kazuo Takechi

发明人： Duk Sung Hwang ,  Evelyn Nario ,  Mark Lepe ,  Lyndon Luz ,  Hirokazu Ito ,  Kazuo Takechi

IPC分类号： C12N9/64 ,  C07K1/14 ,  C07K14/775 ,  C07K14/81 ,  A61K35/14 ,  C07K14/00

CPC分类号： C07K14/775 ,  C07K14/8125 ,  Y10S530/811 ,  Y10S530/812

摘要： The present invention is directed to a process for purifying alpha-1-PI. The process comprises providing an impure protein fraction which comprises alpha-1-PI. The impure protein fraction is suspended in an aqueous solution at pH 6. Insoluble proteins are recovered and resuspended in aqueous solution at pH 8.5. PEG is added to precipitate .alpha.-2 proteins. To the PEG supernatant precipitation, which comprises alpha-1-PI, is added ZnCl.sub.2 to precipitate crude alpha-1-PI. The crude alpha-1-PI is resolubilized and applied to an anion-exchange medium. A fraction comprising alpha-1-PI is recovered from the anion-exchange medium. Alpha-1-PI purified by the process has a specific activity about 1.0 units/OD.sub.280.

摘要翻译： 本发明涉及纯化α-1-PI的方法。 该方法包括提供包含α-1-PI的不纯蛋白质级分。 将不纯的蛋白质级分悬浮在pH6的水溶液中。回收不溶性蛋白质并将其重悬于pH8.5的水溶液中。 添加PEG以沉淀α-2蛋白。 向包含α-1-PI的PEG上清液中加入ZnCl 2以沉淀粗α-1-PI。 将粗α-1-PI重新溶解并施用于阴离子交换介质。 从阴离子交换介质中回收包含α-1-PI的级分。 通过该方法纯化的α-1-PI具有约1.0单位/ OD280的比活度。

公开(公告)号：US4876088A

公开(公告)日：1989-10-24

申请号：US152217

申请日：1988-02-05

申请人： Yutaka Hirao ,  Kazuo Takechi ,  Katuhiro Uriyu ,  Yahiro Uemura

发明人： Yutaka Hirao ,  Kazuo Takechi ,  Katuhiro Uriyu ,  Yahiro Uemura

IPC分类号： A61K9/00 ,  A61K39/395 ,  A61K47/26 ,  C08L89/00

CPC分类号： A61K9/0019 ,  A61K39/39591 ,  A61K47/26

摘要： An intravenously injectable solution of chemically unmodified .gamma.-globulin having a complete molecular structure is disclosed, said solution containing sorbitol as a stabilizer and having a low electrical conductivity and a pH of about 5.5.+-.0.2. The injectable solution does not cause an increase of .gamma.-globulin polymer, a rise of anticomplement titer, or impairment of the activities of the .gamma.-globulin, either during preservation or upon administration to a living body.

公开(公告)号：US4845199A

公开(公告)日：1989-07-04

申请号：US71685

申请日：1987-07-09

申请人： Yutaka Hirao ,  Katuhiro Uriyu ,  Kazuo Takechi ,  Yahiro Uemura

发明人： Yutaka Hirao ,  Katuhiro Uriyu ,  Kazuo Takechi ,  Yahiro Uemura

IPC分类号： A61L2/00

CPC分类号： A61L2/0023 ,  Y10S530/83

摘要： A process for heat treating an aqueous solution containing chemically unmodified .gamma.-globulin, wherein said heat treating is carried out in the presence of sorbitol is disclosed. By the heat treatment, impurity viruses can be inactivated without causing impairment of activities of chemically unmodified .gamma.-globulin, increasing polymer contents or increasing an anticomplement titer.

摘要翻译： 公开了一种用于热处理含有化学未改性的γ-球蛋白的水溶液的方法，其中所述热处理在山梨醇存在下进行。 通过热处理，可以使杂质病毒灭活而不引起化学未改性的γ-球蛋白活性的损害，增加聚合物含量或增加抗补体滴度。

公开(公告)号：US4017470A

公开(公告)日：1977-04-12

申请号：US478884

申请日：1974-06-12

申请人： Ken-ichi Izaka ,  Kazuo Takechi

发明人： Ken-ichi Izaka ,  Kazuo Takechi

IPC分类号： C07K14/76 ,  A61K35/14 ,  A61K38/16 ,  C07K1/30 ,  C07K14/435 ,  C07K14/765 ,  C07G7/00

CPC分类号： C07K1/30 ,  C07K14/765 ,  Y10S530/831

摘要： A heat-stable plasma protein solution showing no blood pressure-depressing action is obtained by adding distilled water to a paste IV-1, a waste fraction obtained from the Cohn's cold ethanol plasma fractionation method and has heretofore been discarded as a waste, to extract water-soluble proteins in the paste, heat-treating the extract at pH 4.5 to 5.5 at 50.degree. to 65.degree. C. in the presence of an organic acid to remove as precipitates lipo- and glyco-proteins contained in the extract, adding Rivanol to the resulting supernatant to remove by precipitation residual lipo-proteins giving turbidity to the supernatant, and then removing blood pressure-depressing substances present in the resulting supernatant by adsorption with an inorganic adsorbent or cation exchanger. The thus obtained heat-stable plasma protein solution shows prominent effects in the therapy of shock by acute bleeding, burns, supply of protein nutrients, hypoproteinemia, etc., and is useful for medical treatments.

摘要翻译： 通过将蒸馏水加入到糊剂IV-1中，通过从科恩氏冷乙醇血浆分级分离方法得到的废液馏分，并将其作为废弃物废弃，从而获得不含血压降低作用的热稳定血浆蛋白质溶液 糊状物中的水溶性蛋白质，在有机酸存在下，在pH 4.5〜5.5的温度下，在50〜65℃下热处理提取物，作为析出物中析出的脂质体和糖蛋白，加入Rivanol 通过沉淀残留的脂蛋白去除上清液，然后通过用无机吸附剂或阳离子交换剂吸附除去存在于所得上清液中的血压降低物质。 由此获得的热稳定性血浆蛋白溶液在急性出血，烧伤，蛋白质营养供应，低蛋白血症等治疗休克方面表现出显着的效果，对于医学治疗是有用的。

公开(公告)号：US6162904A

公开(公告)日：2000-12-19

申请号：US421405

申请日：1999-10-21

申请人： Raja R. Mamidi ,  Andranik Bagdasarian ,  Gorgonio Canaveral ,  Kazuo Takechi

发明人： Raja R. Mamidi ,  Andranik Bagdasarian ,  Gorgonio Canaveral ,  Kazuo Takechi

IPC分类号： C07K16/06 ,  C07K16/00 ,  A61K38/21 ,  C12N7/06

CPC分类号： C07K16/065 ,  A61K2039/505

摘要： A process for producing an intravenously-administrable gamma globulin solution substantially free of contaminating viruses by heat treating for viral inactivation and fractionating an impure gamma globulin solution and then treating the purified gamma globulin with a solvent-detergent for further viral inactivation. In a continuous process disclosed herein, partially purified gamma globulin solids is not recovered as an intermediate product during the disclosed process. In the continuous process, the fractionation to obtain a purified gamma globulin solution is carried out without precipitation of the desired gamma globulin.

摘要翻译： 用于通过热处理用于病毒灭活并分级分离不纯的γ球蛋白溶液，然后用溶剂洗涤剂处理纯化的γ球蛋白以进一步病毒灭活来生产基本上不含污染病毒的静脉内施用的γ球蛋白溶液的方法。 在本文公开的连续方法中，部分纯化的γ球蛋白固体在所公开的方法中不作为中间产物回收。 在连续方法中，获得纯化的γ球蛋白溶液的分级进行而不沉淀所需的γ球蛋白。