公开(公告)号：US4996299A

公开(公告)日：1991-02-26

申请号：US442148

申请日：1989-11-28

申请人： Akihiro Ginnaga ,  Kazunori Morokuma ,  Katsutoshi Aihara ,  Mitsuo Sakoh

发明人： Akihiro Ginnaga ,  Kazunori Morokuma ,  Katsutoshi Aihara ,  Mitsuo Sakoh

IPC分类号： C12N1/20 ,  A61K38/36 ,  A61K39/10 ,  A61P37/00

CPC分类号： A61K39/099 ,  Y10S530/825

摘要： Disclosed is a method for preparing pertussis toxin toxoid by a treatment pertussis toxin with formaldehyde, which comprises carrying out said treatment in the presence of lysine or glycine in combination with N-acetyltriptophan. The resultant toxoid does not exhibit toxicity reversion, thereby making the toxoid highly suitable for use in pertussis vaccines.

公开(公告)号：US4885359A

公开(公告)日：1989-12-05

申请号：US122576

申请日：1987-11-16

申请人： Akihiro Ginnaga ,  Tsukasa Nishihara ,  Tetsuo Kawahara ,  Sadao Susumi ,  Hiroshi Mizokami ,  Mitsuo Sakoh

发明人： Akihiro Ginnaga ,  Tsukasa Nishihara ,  Tetsuo Kawahara ,  Sadao Susumi ,  Hiroshi Mizokami ,  Mitsuo Sakoh

IPC分类号： A61K39/10 ,  A61K39/00 ,  C07K14/235

CPC分类号： C07K14/235 ,  A61K39/00 ,  Y10S435/803 ,  Y10S530/825

摘要： Improved method for the purification of LPF-HA (Leucocytosis promoting far hemagglutinin) on industrial scale which comprises contacting a LPF-HA-containing solution from culture media of Bordetella pertussis with a cellulose sulfate gel, a crosslinked polysaccharide sulfate gel, or a polysaccharide gel chemically bound with dextran sulfate, thereby adsorbing LPF-HA on the gel, and then eluting LPF-HA from the gel. Said method can give a highly purified LPF-HA which does not contain any other proteins, lipid, saccharides, etc. and further undesirable endotoxin, and hence can be used for producing various reagents, medicines and pertussis vaccine.

摘要翻译： 用于在工业规模上纯化LPF-HA（白细胞促进因子血凝素）的改进方法，其包括使来自百日咳博德特氏菌培养基的含LPF-HA的溶液与硫酸纤维素凝胶，交联多糖硫酸酯凝胶或多糖凝胶 与硫酸葡聚糖化学结合，从而在凝胶上吸附LPF-HA，然后从凝胶洗脱LPF-HA。 所述方法可以得到不含任何其它蛋白质，脂质，糖类等的高度纯化的LPF-HA，还可以产生不希望的内毒素，因此可用于生产各种试剂，药物和百日咳疫苗。

公开(公告)号：US20110105940A1

公开(公告)日：2011-05-05

申请号：US12673980

申请日：2008-08-20

申请人： Yasushi Torii ,  Tetsuhiro Harakawa ,  Yoshitaka Goto ,  Akihiro Ginnaga ,  Ryuji Kaji ,  Shunji Kozaki ,  Motohide Takahashi

发明人： Yasushi Torii ,  Tetsuhiro Harakawa ,  Yoshitaka Goto ,  Akihiro Ginnaga ,  Ryuji Kaji ,  Shunji Kozaki ,  Motohide Takahashi

IPC分类号： A61B5/0488

CPC分类号： G01N33/6854 ,  A61B5/0488 ,  G01N2333/33 ,  G01N2469/20

摘要： A method for quantification of a titer of a neutralizing antibody to a neurotoxin is disclosed. The method comprises the steps: (a) mixing a standard sample containing a fixed amount of a neurotoxin and a test sample containing a neutralizing antibody to said neurotoxin; (b) administering the mixture obtained in step (a) into the muscle of a non-human mammal; (c) applying electric stimulus to said non-human mammal; (d) measuring a compound muscle action potential (CMAP) due to contraction of the muscle of said mammal by application of electric stimulus with an electromyograph; and (e) analyzing CMAP amplitude data obtained in step (d) for an extent of decrease in amplitude by a non-neutralized neurotoxin to thereby quantify a titer of the neutralizing antibody contained in the test sample.

摘要翻译： 公开了定量神经毒素中和抗体滴度的方法。 该方法包括以下步骤：（a）将含有固定量的神经毒素的标准样品和含有中和抗体的测试样品与所述神经毒素混合; （b）将步骤（a）中获得的混合物给予非人哺乳动物的肌肉; （c）对所述非人哺乳动物施加电刺激; （d）通过用肌电图仪施加电刺激来测量由于所述哺乳动物的肌肉收缩引起的复合肌肉动作电位（CMAP）; 和（e）通过未中和的神经毒素分析在步骤（d）中获得的CMAP振幅数据的幅度减小，从而定量测试样品中所含的中和抗体的滴度。

公开(公告)号：US4687738A

公开(公告)日：1987-08-18

申请号：US874670

申请日：1986-06-16

申请人： Akihiro Ginnaga ,  Hiroshi Koba ,  Shin Sakuma ,  Hisashi Kitagawa ,  Akira Yamada ,  Yoji Suzuki

发明人： Akihiro Ginnaga ,  Hiroshi Koba ,  Shin Sakuma ,  Hisashi Kitagawa ,  Akira Yamada ,  Yoji Suzuki

IPC分类号： A61K39/10 ,  A61K39/00 ,  C07K14/235 ,  C12P21/00

CPC分类号： C07K14/235 ,  A61K39/00 ,  Y10S435/802 ,  Y10S435/812 ,  Y10S435/813 ,  Y10S435/822

摘要： A method for production of HA fraction containing protective antigens of Bordetella pertussis (i.e. a fraction containing F-HA and LPF-HA) in an industrial scale, for instance, with a fermentater, which comprises inoculating a strain of B. pertussis in a liquid culture containing a cyclodextrin or its derivative, culturing it by a spinner culture under controlling the culture temperature and the amount of dissolved oxygen and under defoaming condition, optionally under controlling the pH range, and harvesting the produced HA fraction from the culture broth at a stage of from logarithmic growth phase to static grow phase, and a method for production of a pertussis vaccine from the HA fraction thus obtained by formalinizing the HA fraction in the presence of an amino acid.

摘要翻译： 一种生产含有百日咳博德特氏菌（即含有F-HA和LPF-HA的部分）的HA级分的HA级分的方法，例如用发酵罐，其包括将百日咳杆菌菌株接种在液体中 含有环糊精或其衍生物的培养物，在控制培养温度和溶解氧量以及消泡条件下，任选地控制pH范围内，通过旋转培养物进行培养，并在培养液中收获生成的HA级分 从对数生长期到静态生长阶段，以及通过在氨基酸存在下对HA级分进行福尔马林处理从HA馏分产生百日咳疫苗的方法。

公开(公告)号：US4563303A

公开(公告)日：1986-01-07

申请号：US722381

申请日：1985-04-12

申请人： Akihiro Ginnaga ,  Shin Sakuma ,  Tsukasa Nishihara ,  Tomitaka Tashiro ,  Sadao Susumi ,  Tetsuo Kawahara ,  Hiroshi Mizokami

发明人： Akihiro Ginnaga ,  Shin Sakuma ,  Tsukasa Nishihara ,  Tomitaka Tashiro ,  Sadao Susumi ,  Tetsuo Kawahara ,  Hiroshi Mizokami

IPC分类号： C12P21/00 ,  A61K39/00 ,  C07K14/235 ,  A61K39/10

CPC分类号： C07K14/235 ,  A61K39/00 ,  Y10S435/822 ,  Y10S530/825

摘要： Improved method for the purification of filamentous hemagglutinin (F-HA) on industrial scale which comprises contacting a culture of a microorganism of the genus Bordetella with a cellulose sulfate gel, a polysaccharide gel chemically bound with dextran sulfate, or a crosslinked polysaccharide sulfate gel, thereby adsorbing F-HA on the gel, and then eluting F-HA from the gel. Said method can give a highly purified F-HA which does not contain any other proteins, lipid, saccharides, etc. and further undesirable endotoxin, and hence can be used for producing various reagents, medicines and pertussis vaccine.

摘要翻译： 用于工业规模净化丝状血凝素（F-HA）的改进方法，其包括将博德特氏菌属的微生物的培养物与硫酸纤维素凝胶接触，与硫酸葡聚糖化学结合的多糖凝胶或交联的多糖硫酸凝胶， 从而在凝胶上吸附F-HA，然后从凝胶中洗脱F-HA。 所述方法可以得到不含任何其它蛋白质，脂质，糖类等的高度纯化的F-HA，以及不希望的内毒素，因此可用于生产各种试剂，药物和百日咳疫苗。