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1. 发明授权

US08540987B2 Composition for neutralizing botulinus toxin type-A, and human anti-botulinus toxin type-A antibody 有权
标题翻译：用于中和A型肉毒杆菌毒素和A型抗人类肉毒毒素毒素的组合物
公开(公告)号：US08540987B2
公开(公告)日：2013-09-24
申请号：US12864018
申请日：2009-01-23
申请人： Masachika Azuma , Motohide Takahashi , Shunji Kozaki , Masafumi Mukamoto , Tomoko Kohda , Gene Kurosawa , Yoshikazu Kurosawa
发明人： Masachika Azuma , Motohide Takahashi , Shunji Kozaki , Masafumi Mukamoto , Tomoko Kohda , Gene Kurosawa , Yoshikazu Kurosawa
IPC分类号： A61K39/395 , A61K39/00 , C07K16/00 , C12P21/08
CPC分类号： C07K16/1282 , A61K2039/505 , A61K2039/507 , C07K2317/21 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/92
摘要： Provided herein is a means which is effective for botulism diseases and the prevention of the botulism diseases. Specifically provided is a plurality of human anti-botulinum toxin type-A antibodies having different epitopes from one another. Also specifically provided is a composition for neutralizing botulinum toxin type-A, which comprises a combination of two or more of the antibodies and which has a high neutralizing activity.
摘要翻译：本文提供了对肉毒中毒疾病和预防肉毒杆菌病有效的手段。具体提供的是具有彼此具有不同表位的多种人类抗 - 肉毒毒素A型抗体。还具体提供了用于中和A型肉毒杆菌毒素的组合物，其包含两种或更多种抗体的组合并且具有高中和活性。

2. 发明申请

US20110014211A1 COMPOSITION FOR NEUTRALIZING BOTULINUS TOXIN TYPE-A, AND HUMAN ANTI-BOTULINUS TOXIN TYPE-A ANTIBODY 有权
标题翻译：用于中性粒细胞毒素A型的组合物和人抗胰蛋白酶类型A抗体
公开(公告)号：US20110014211A1
公开(公告)日：2011-01-20
申请号：US12864018
申请日：2009-01-23
申请人： Masachika Azuma , Motohide Takahashi , Shunji Kozaki , Masafumi Mukamoto , Tomoko Kohda , Gene Kurosawa , Yoshikazu Kurosawa
发明人： Masachika Azuma , Motohide Takahashi , Shunji Kozaki , Masafumi Mukamoto , Tomoko Kohda , Gene Kurosawa , Yoshikazu Kurosawa
IPC分类号： A61K39/40 , A61P31/04
CPC分类号： C07K16/1282 , A61K2039/505 , A61K2039/507 , C07K2317/21 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/92
摘要： Provided herein is a means which is effective for botulism diseases and the prevention of the botulism diseases. Specifically provided is a plurality of human anti-botulinum toxin type-A antibodies having different epitopes from one another. Also specifically provided is a composition for neutralizing botulinum toxin type-A, which comprises a combination of two or more of the antibodies and which has a high neutralizing activity.
摘要翻译：本文提供了对肉毒中毒疾病和预防肉毒杆菌病有效的手段。具体提供的是具有彼此具有不同表位的多种人类抗 - 肉毒毒素A型抗体。还具体提供了用于中和A型肉毒杆菌毒素的组合物，其包含两种或更多种抗体的组合并且具有高中和活性。

3. 发明申请

US20110105940A1 METHOD FOR QUANTIFICATION OF TITER OF NEUTRALIZING ANTIBODY TO NEUROTOXIN 审中-公开
标题翻译：中性抗体对神经毒素的定量的方法
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。

4. 发明申请

US20130252902A1 TYPE A2 BOTULINUM TOXIN PREPARATION 审中-公开
标题翻译： A2型BOTULINUM毒素制剂
公开(公告)号：US20130252902A1
公开(公告)日：2013-09-26
申请号：US13903731
申请日：2013-05-28
申请人： Shinji NAKAHIRA , Yasushi Torii , Yoshitaka Goto , Miho Shinmura , Satomi Munechika , Sachio Okuda , Shunji Kozaki
发明人： Shinji NAKAHIRA , Yasushi Torii , Yoshitaka Goto , Miho Shinmura , Satomi Munechika , Sachio Okuda , Shunji Kozaki
IPC分类号： A61K38/16
CPC分类号： A61K38/164 , A61K38/4893 , Y02A50/469
摘要： A method for treating a patient who has a neutralizing antibody to a type A1 botulinum toxin. The method includes administering 150 kDa type A neurotoxin from type A2 Clostridium botulinum (A2 NTX) to the patient. In accordance with the present invention, a problem can be solved of decrease in clinical response caused by a neutralizing antibody to a type A1 botulinum toxin produced when a patient is treated with a pharmaceutical preparation containing a type A1 botulinum toxin.
摘要翻译：一种治疗患有A1型肉毒杆菌毒素中和抗体的患者的方法。该方法包括从A2型肉毒杆菌（A2NTX）向患者施用150kDa的A型神经毒素。根据本发明，当患者用含有A1型肉毒杆菌毒素的药物制剂治疗时，可以解决由中和抗体对产生的A1型肉毒杆菌毒素引起的临床反应降低的问题。

5. 发明申请

US20110033431A1 TYPE A2 BOTULINUM TOXIN PREPARATION 审中-公开
标题翻译： A2型BOTULINUM毒素制剂
公开(公告)号：US20110033431A1
公开(公告)日：2011-02-10
申请号：US12935769
申请日：2009-03-31
申请人： Shinji Nakahira , Yasushi Torii , Yoshitaka Goto , Miho Shinmura , Satomi Munechika , Sachio Okuda , Shunji Kozaki
发明人： Shinji Nakahira , Yasushi Torii , Yoshitaka Goto , Miho Shinmura , Satomi Munechika , Sachio Okuda , Shunji Kozaki
IPC分类号： A61K35/74 , A61P21/00 , C12N1/20 , C07K14/33
CPC分类号： A61K38/164 , A61K38/4893 , Y02A50/469
摘要： A pharmaceutical preparation for use in a patient who has a neutralizing antibody to a botulinum toxin from type A1 Clostridium botulinum (type A1 botulinum toxin), said preparation comprising as an active ingredient 150 kDa type A neurotoxin from type A2 Clostridium botulinum (A2 NTX); a medicament for treating a disease with muscle overactivity for use in a patient who has a neutralizing antibody to a type A1 botulinum toxin, said medicament comprising as an active ingredient said A2 NTX; a method for treating a patient who has a neutralizing antibody to a type A1 botulinum toxin, said method comprising administering said A2 NTX to the patient; and a method for use of A2 NTX in a patient who has said neutralizing antibody. In accordance with the present invention, a problem can be solved of decrease in clinical response caused by a neutralizing antibody to a type A1 botulinum toxin produced when a patient is treated with a pharmaceutical preparation comprising a type A1 botulinum toxin.
摘要翻译：一种用于患有来自A1型肉毒毒素（A1型肉毒杆菌毒素）的肉毒毒素中和抗体的患者的药物制剂，所述制剂包含来自A2型肉毒毒素（A2NTX）的150kDa A型神经毒素作为活性成分， ; 用于治疗患有肌肉过度活动的疾病的药物，所述疾病用于患有A1型肉毒杆菌毒素的中和抗体的患者，所述药物包含所述A2NXX的活性成分; 用于治疗对A1型肉毒杆菌毒素具有中和抗体的患者的方法，所述方法包括向患者施用所述A2NXX; 以及在具有所述中和抗体的患者中使用A2NTX的方法。根据本发明，当患者用包含A1型肉毒杆菌毒素的药物制剂治疗时，可以解决由中和抗体对产生的A1型肉毒杆菌毒素引起的临床反应降低的问题。

6. 发明申请

US20050163809A1 Remedy for hypermyotonia 审中-公开
标题翻译：治疗肌张力障碍的治疗方法
公开(公告)号：US20050163809A1
公开(公告)日：2005-07-28
申请号：US10508980
申请日：2003-03-31
申请人： Ryuji Kaji , Shunji Kozaki , Keiji Oguma
发明人： Ryuji Kaji , Shunji Kozaki , Keiji Oguma
IPC分类号： A61K38/48 , A61P21/02 , A61P25/00 , A61P25/14 , A61P27/02 , A61P43/00 , A61K39/08
CPC分类号： A61K38/4886
摘要： A remedy for muscle hyperactivity, comprising a purified botulinum neurotoxin as an active ingredient.
摘要翻译：肌肉多动症的补救措施，包括纯化的肉毒杆菌神经毒素作为活性成分。

7. 发明授权

US06197282B1 Fine ultraviolet screening particles, process for preparing the same, and cosmetic preparation 有权
标题翻译：精细的紫外线筛选颗粒，其制备方法和化妆品制备
公开(公告)号：US06197282B1
公开(公告)日：2001-03-06
申请号：US09194199
申请日：1998-11-20
申请人： Kentaro Oshima , Shunji Kozaki , Yoshinobu Imaizumi , Toshio Miyake , Keiichi Tsuto , Kazuhiro Yamaki , Satoshi Sugawara
发明人： Kentaro Oshima , Shunji Kozaki , Yoshinobu Imaizumi , Toshio Miyake , Keiichi Tsuto , Kazuhiro Yamaki , Satoshi Sugawara
IPC分类号： A61K742
CPC分类号： C01G23/047 , A61K8/0241 , A61K8/27 , A61K8/29 , A61K2800/412 , A61K2800/624 , A61Q17/04 , C01G9/02 , C01P2004/62 , C09C1/3684
摘要： The present invention provides a method for producing a material dispersed with ultraviolet shielding fine particles, characterized by subjecting a starting material liquid mixture comprising particles comprising one or more inorganic substances having shielding abilities against ultraviolet light, one or more silicone dispersants selected from modified silicones and reactive silicones, and a silicone oil to a mill treatment and/or a high-pressure dispersion treatment; and ultraviolet shielding fine particles or a material dispersed therewith, characterized by being produced by the above method. Also, the present invention provides a method of producing a powdery product of ultraviolet shielding fine particles, characterized by drying the material dispersed with ultraviolet shielding fine particles obtainable by the above method. Further, the present invention provides cosmetics comprising a material dispersed with ultraviolet shielding fine particles or a powdery product of the ultraviolet shielding fine particles. The material dispersed with ultraviolet shielding fine particles of the present invention is characterized in that the ultraviolet shielding fine particles comprise particles comprising one or more inorganic substances having shielding abilities against ultraviolet light, surfaces thereof being coated with one or more silicone dispersants selected from modified silicones and reactive silicones, and that at least a part of the ultraviolet shielding fine particles is dispersed in a silicone oil as aggregated particles of the particles comprising inorganic substances.
摘要翻译：本发明提供一种分散有紫外线屏蔽微粒的材料的制造方法，其特征在于，将包含一种或多种具有屏蔽能力的无机物质的紫外线的原料液体混合物，一种或多种选自改性硅酮的有机硅分散剂和反应性硅氧烷和硅油进行研磨处理和/或高压分散处理; 和紫外线屏蔽微粒或其分散的材料，其特征在于通过上述方法制备。另外，本发明提供一种紫外线屏蔽微粒的粉末状制品的制造方法，其特征在于，使用通过上述方法得到的紫外线屏蔽微粒分散的材料进行干燥。此外，本发明提供了包含分散有紫外线屏蔽微粒的材料或紫外线屏蔽微粒的粉末状产品的化妆品。用本发明的紫外线屏蔽微粒分散的材料的特征在于，紫外线屏蔽微粒包括包含一种或多种具有对紫外线的屏蔽能力的无机物质的颗粒，其表面涂覆有一种或多种选自改性有机硅的硅氧烷分散剂和反应性硅氧烷，并且至少一部分紫外线屏蔽细颗粒作为包含无机物质的颗粒的凝集颗粒分散在硅油中。

8. 发明授权

US09623075B2 Type A2 botulinum toxin preparation 有权
公开(公告)号：US09623075B2
公开(公告)日：2017-04-18
申请号：US13903731
申请日：2013-05-28
申请人： Shinji Nakahira , Yasushi Torii , Yoshitaka Goto , Miho Shinmura , Satomi Munechika , Sachio Okuda , Shunji Kozaki
发明人： Shinji Nakahira , Yasushi Torii , Yoshitaka Goto , Miho Shinmura , Satomi Munechika , Sachio Okuda , Shunji Kozaki
IPC分类号： A61K38/48 , A61K38/16
CPC分类号： A61K38/164 , A61K38/4893 , Y02A50/469
摘要： A method for treating a patient who has a neutralizing antibody to a type A1 botulinum toxin. The method includes administering 150 kDa type A neurotoxin from type A2 Clostridium botulinum (A2 NTX) to the patient. In accordance with the present invention, a problem can be solved of decrease in clinical response caused by a neutralizing antibody to a type A1 botulinum toxin produced when a patient is treated with a pharmaceutical preparation containing a type A1 botulinum toxin.

9. 发明授权

US5902569A Ultraviolet shielding composite fine particles, method for producing the same, and cosmetics 失效
标题翻译：紫外线屏蔽复合微粒，其制造方法和化妆品
公开(公告)号：US5902569A
公开(公告)日：1999-05-11
申请号：US894672
申请日：1997-08-27
申请人： Kentaro Oshima , Shunji Kozaki , Yoshinobu Imaizumi , Toshio Miyake , Toru Nishimura , Keiichi Tsuto , Satoshi Sugawara , Makoto Torizuka
发明人： Kentaro Oshima , Shunji Kozaki , Yoshinobu Imaizumi , Toshio Miyake , Toru Nishimura , Keiichi Tsuto , Satoshi Sugawara , Makoto Torizuka
IPC分类号： A61K8/04 , A61K8/06 , A61Q1/02 , A61Q1/06 , A61Q1/10 , A61Q17/04 , C09C1/00 , C09C1/30 , C09C1/64 , A61K7/42 , A61K6/00 , A61K7/44 , A61K9/00
CPC分类号： C09C1/0081 , A61K8/0287 , A61K8/06 , A61Q1/02 , A61Q1/06 , A61Q1/10 , A61Q17/04 , B82Y30/00 , B82Y5/00 , A61K2800/262 , A61K2800/413 , C01P2002/84 , C01P2004/03 , C01P2004/04 , C01P2004/10 , C01P2004/20 , C01P2004/32 , C01P2004/50 , C01P2004/62 , C01P2004/64 , C01P2004/82 , C01P2004/84 , C01P2006/60 , C01P2006/80 , C01P2006/90
摘要： The present invention is directed to ultraviolet shielding composite fine particles having transparency in a visible light region include (a) matrix particles comprising an aggregate of primary particles having an average particle diameter of from 0.001 to 0.3 .mu.m, the aggregate being formed while the primary particles retain their shapes; and (b) daughter particles having an average particle diameter of from 0.001 to 0.1 .mu.m, the daughter particles being dispersed in and supported by the matrix particles. In the composite fine particles, the daughter particles have a smaller band gap energy than the particles constituting the matrix particles and are capable of absorbing ultraviolet light, and the resulting ultraviolet shielding composite fine particles have substantially no catalytic activity.
摘要翻译： PCT No.PCT / JP96 / 00593 Sec。 371日期1997年8月27日第 102（e）日期1997年8月27日PCT PCT 1996年3月7日PCT公布。公开号WO96 / 28137 日期1996年9月19日本发明涉及在可见光区域具有透明性的紫外线屏蔽复合微粒子，其包含（a）基质颗粒，其包含平均粒径为0.001〜0.3μm的一次粒子的聚集体，在初级颗粒保持其形状时形成; 和（b）平均粒径为0.001〜0.1μm的子粒子，所述子粒分散在基质颗粒中并由基质颗粒支撑。在复合微粒子中，子粒子具有比构成基体粒子的粒子更小的带隙能量，能够吸收紫外线，所得到的紫外线屏蔽复合微粒基本上没有催化活性。

10. 发明申请

US20060153877A1 Remedies for dissease with hypermyotonia 审中-公开
标题翻译：解除与肌张力减退的补救措施
公开(公告)号：US20060153877A1
公开(公告)日：2006-07-13
申请号：US10560789
申请日：2004-06-18
申请人： Shunji Kozaki , Nakaba Sugimoto , Masamitsu Shimazawa , Hideaki Hara
发明人： Shunji Kozaki , Nakaba Sugimoto , Masamitsu Shimazawa , Hideaki Hara
IPC分类号： A61K39/08 , C12P21/06 , C12N1/20
CPC分类号： A61K38/4893 , Y02A50/469
摘要： An M toxin of type A botulinum toxin (HA-negative substance) and a mixture of L toxin and LL toxin (HA-positive substance) are compared and examined in inhibitory action for neuromuscular transmission and therapeutic index. As a result, it is found that M toxin of type A botulinum toxin has characteristics of: 1) having an excellent inhibitory action for neuromuscular transmission; 2)showing a high therapeutic index; 3) showing a low antigenicity and 4) suffering from little reduction in efficacy even after repeatedly administered, compared with the mixture of L toxin and LL toxin. Owing to these characterics, the M toxin of type A botulinum toxin is particularly useful as a therapeutic agent for diseases caused by hypermyotonia such as strabismus, blepharospasm, facial spasms, spasmodic torticollis, paralysis after cerebral apoplexy, infantile cerebral paralysis, spasmodic phonopathy, headache such as migraine, chronic pain such as lumbago, stiff shoulder, muscular relaxation disorder accompanied with onset of Parkinson's disease or multiple sclerosis, myofascial pain syndrome, masticatory spasm, chronic anal fissure, urinary inconsistency, grinding of teeth, facial myokymia, tic, topical dystonia and wrinkles.
摘要翻译：对A型肉毒杆菌毒素（HA-阴性物质）的M毒素和L毒素和LL毒素（HA-阳性物质）的混合物进行比较和检测，用于神经肌肉传播和治疗指数的抑制作用。结果发现A型肉毒杆菌毒素的M毒素具有以下特征：1）对神经肌肉传递具有优异的抑制作用; 2）显示高治疗指数; 3）显示低抗原性，4）与L毒素和LL毒素的混合物相比，即使在重复施用后也几乎没有功效降低。由于这些特征，A型肉毒杆菌毒素的M毒素特别可用作由肌腱炎，如斜视，眼睑痉挛，面部痉挛，痉挛性斜颈，脑中风后麻痹，婴儿脑性麻痹，痉挛性神经病，头痛等疾病引起的疾病的治疗剂如偏头痛，慢性疼痛如腰痛，肩膀僵硬，伴有帕金森病或多发性硬化症发作的肌肉弛豫障碍，肌筋膜疼痛综合征，咀嚼性痉挛，慢性肛裂，尿不一致，牙齿研磨，面部肌无力，局部肌张力障碍和皱纹。

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