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1. 发明申请

US20090093414A1 Hyaluronic Acid-Methotrexate Conjugate 有权
标题翻译：透明质酸 - 甲氨蝶呤结合物
公开(公告)号：US20090093414A1
公开(公告)日：2009-04-09
申请号：US11547158
申请日：2005-04-01
申请人： Hitoshi Ikeya , Tadashi Morikawa , Koichi Takahashi , Noriyuki Izutani , Tatsuya Tamura , Akira Okamachi , Takenori Ishizawa , Haruhiko Sato , Yoshinobu Higuchi , Tatsuya Kato , Akie Honma
发明人： Hitoshi Ikeya , Tadashi Morikawa , Koichi Takahashi , Noriyuki Izutani , Tatsuya Tamura , Akira Okamachi , Takenori Ishizawa , Haruhiko Sato , Yoshinobu Higuchi , Tatsuya Kato , Akie Honma
IPC分类号： A61K31/728 , A61K38/03 , C07K2/00 , C07H3/00 , C07D475/00
CPC分类号： C08L5/08 , A61K31/519 , A61K47/61 , A61K47/65 , C07D475/08 , C08B37/0072
摘要： An object of the present invention is to provide a hyaluronic acid-methotrexate conjugate useful as a therapeutic drug for joint disorders. There is provided a hyaluronic acid-methotrexate conjugate useful for the treatment of joint disorders, wherein methotrexate is conjugated with a hydroxy group of hyaluronic acid through a linker containing a peptide chain consisting of 1 to 8 amino acids, and the linker is conjugated with the hyaluronic acid through a carbamate group.
摘要翻译：本发明的目的是提供可用作关节病的治疗药物的透明质酸 - 甲氨蝶呤缀合物。提供了可用于治疗关节疾病的透明质酸 - 甲氨蝶呤缀合物，其中甲氨蝶呤通过含有1至8个氨基酸的肽链的接头与透明质酸的羟基缀合，并且接头与透明质酸通过氨基甲酸酯基团。

2. 发明授权

US08088916B2 Hyaluronic acid-methotrexate conjugate 有权
标题翻译：透明质酸 - 甲氨蝶呤结合物
公开(公告)号：US08088916B2
公开(公告)日：2012-01-03
申请号：US10591653
申请日：2005-03-04
申请人： Hitoshi Ikeya , Tadashi Morikawa , Koichi Takahashi , Tatsuya Tamura , Akira Okamachi , Takenori Ishizawa , Haruhiko Sato , Yoshinobu Higuchi
发明人： Hitoshi Ikeya , Tadashi Morikawa , Koichi Takahashi , Tatsuya Tamura , Akira Okamachi , Takenori Ishizawa , Haruhiko Sato , Yoshinobu Higuchi
IPC分类号： C08B37/00 , A01N43/04 , A01N43/60
CPC分类号： C08B37/0072 , A61K47/61 , A61K47/65 , C07D475/08 , C07K9/003
摘要： An object of the present invention is to provide a hyaluronic acid-methotrexate conjugate useful as a therapeutic drug for joint diseases.There is provided a hyaluronic acid-methotrexate conjugate useful as a therapeutic drug for joint diseases, wherein methotrexate is conjugated with a carboxyl group of hyaluronic acid through a linker containing a peptide chain consisting of 1 to 8 amino acids.
摘要翻译：本发明的目的是提供可用作关节疾病的治疗药物的透明质酸 - 甲氨蝶呤缀合物。提供了可用作关节疾病的治疗药物的透明质酸 - 甲氨蝶呤缀合物，其中甲氨蝶呤通过含有1至8个氨基酸的肽链的接头与透明质酸的羧基缀合。

3. 发明授权

US07807675B2 Hyaluronic acid-methotrexate conjugate 有权
标题翻译：透明质酸 - 甲氨蝶呤结合物
公开(公告)号：US07807675B2
公开(公告)日：2010-10-05
申请号：US11547158
申请日：2005-04-01
申请人： Hitoshi Ikeya , Tadashi Morikawa , Koichi Takahashi , Noriyuki Izutani , Tatsuya Tamura , Akira Okamachi , Takenori Ishizawa , Haruhiko Sato , Yoshinobu Higuchi , Tatsuya Kato , Akie Honma
发明人： Hitoshi Ikeya , Tadashi Morikawa , Koichi Takahashi , Noriyuki Izutani , Tatsuya Tamura , Akira Okamachi , Takenori Ishizawa , Haruhiko Sato , Yoshinobu Higuchi , Tatsuya Kato , Akie Honma
IPC分类号： C07D475/00 , A61K31/715
CPC分类号： C08L5/08 , A61K31/519 , A61K47/61 , A61K47/65 , C07D475/08 , C08B37/0072
摘要： An object of the present invention is to provide a hyaluronic acid-methotrexate conjugate useful as a therapeutic drug for joint disorders. There is provided a hyaluronic acid-methotrexate conjugate useful for the treatment of joint disorders, wherein methotrexate is conjugated with a hydroxy group of hyaluronic acid through a linker containing a peptide chain consisting of 1 to 8 amino acids, and the linker is conjugated with the hyaluronic acid through a carbamate group.
摘要翻译：本发明的目的是提供一种可用作关节病的治疗药物的透明质酸 - 甲氨蝶呤缀合物。提供了可用于治疗关节疾病的透明质酸 - 甲氨蝶呤缀合物，其中甲氨蝶呤通过含有1至8个氨基酸的肽链的接头与透明质酸的羟基缀合，并且接头与透明质酸通过氨基甲酸酯基团。

4. 发明申请

US20070197465A1 Hyaluronic Acid-Methotrexate Conjugate 有权
标题翻译：透明质酸 - 甲氨蝶呤结合物
公开(公告)号：US20070197465A1
公开(公告)日：2007-08-23
申请号：US10591653
申请日：2005-03-04
申请人： Hitoshi Ikeya , Tadashi Morikawa , Koichi Takahashi , Tatsuya Tamura , Akira Okamachi , Takenori Ishizawa , Haruhiko Sato , Yoshinobu Higuchi
发明人： Hitoshi Ikeya , Tadashi Morikawa , Koichi Takahashi , Tatsuya Tamura , Akira Okamachi , Takenori Ishizawa , Haruhiko Sato , Yoshinobu Higuchi
IPC分类号： A61K31/728 , C08B37/00 , A61K31/525
CPC分类号： C08B37/0072 , A61K47/61 , A61K47/65 , C07D475/08 , C07K9/003
摘要： An object of the present invention is to provide a hyaluronic acid-methotrexate conjugate useful as a therapeutic drug for joint diseases. There is provided a hyaluronic acid-methotrexate conjugate useful as a therapeutic drug for joint diseases, wherein methotrexate is conjugated with a carboxyl group of hyaluronic acid through a linker containing a peptide chain consisting of 1 to 8 amino acids.
摘要翻译：本发明的目的是提供可用作关节疾病的治疗药物的透明质酸 - 甲氨蝶呤缀合物。提供了可用作关节疾病的治疗药物的透明质酸 - 甲氨蝶呤缀合物，其中甲氨蝶呤通过含有1至8个氨基酸的肽链的接头与透明质酸的羧基缀合。

5. 发明授权

US09072791B2 Photostabilized pharmaceutical compositions 有权
标题翻译：光稳定药物组合物
公开(公告)号：US09072791B2
公开(公告)日：2015-07-07
申请号：US13121852
申请日：2009-09-30
申请人： Koichi Takahashi , Tadashi Morikawa , Tadao Yamazaki , Masaki Shibata
发明人： Koichi Takahashi , Tadashi Morikawa , Tadao Yamazaki , Masaki Shibata
IPC分类号： A01N43/04 , A61K31/715 , A01N43/90 , A61K31/519 , A61K47/48 , A61K9/00 , A61K9/08 , A61K45/06
CPC分类号： A61K47/4823 , A61K9/0019 , A61K9/08 , A61K45/06 , A61K47/61
摘要： A crosslinking reaction and a reaction for reducing molecular weight that take place in a hyaluronic acid-methotrexate conjugate upon irradiation with light are suppressed to improve the photostability of the conjugate. Specifically, a substance having a quenching effect and/or a radical scaveng effect is added to a pharmaceutical composition containing the hyaluronic acid-methotrexate conjugate.
摘要翻译：抑制交联反应和用于降低在光照射时在透明质酸 - 甲氨蝶呤偶联物中发生的分子量的反应，以提高缀合物的光稳定性。具体地说，将具有淬灭效果和/或自由基清除作用的物质加入到含有透明质酸 - 甲氨蝶呤缀合物的药物组合物中。

6. 发明申请

US20110245276A1 PHOTOSTABILIZED PHARMACEUTICAL COMPOSITIONS 有权
标题翻译：光化学药物组合物
公开(公告)号：US20110245276A1
公开(公告)日：2011-10-06
申请号：US13121852
申请日：2009-09-30
申请人： Koichi Takahashi , Tadashi Morikawa , Tadao Yamazaki , Masaki Shibata
发明人： Koichi Takahashi , Tadashi Morikawa , Tadao Yamazaki , Masaki Shibata
IPC分类号： A61K31/519 , A61P19/02 , A61B17/00
CPC分类号： A61K47/4823 , A61K9/0019 , A61K9/08 , A61K45/06 , A61K47/61
摘要： A crosslinking reaction and a reaction for reducing molecular weight that take place in a hyaluronic acid-methotrexate conjugate upon irradiation with light are suppressed to improve the photostability of the conjugate. Specifically, a substance having a quenching effect and/or a radical scaveng effect is added to a pharmaceutical composition containing the hyaluronic acid-methotrexate conjugate.
摘要翻译：抑制交联反应和用于降低在光照射时在透明质酸 - 甲氨蝶呤偶联物中发生的分子量的反应，以提高缀合物的光稳定性。具体地说，将具有淬灭效果和/或自由基清除作用的物质加入到含有透明质酸 - 甲氨蝶呤缀合物的药物组合物中。

7. 发明申请

US20130203697A1 CROSSLINKED HYALURONIC ACID COMPOSITION AND SELF-CROSSLINKING HYALURONIC ACID PARTICLES 有权
标题翻译：交联羟基酸组合物和自交联羟丙酸颗粒
公开(公告)号：US20130203697A1
公开(公告)日：2013-08-08
申请号：US13818848
申请日：2011-08-23
申请人： Masamichi Hashimoto , Tadashi Morikawa , Yoshiaki Miyata , Akio Ohno , Kei Takahashi , Daisuke Ogasawara , Kenji Fujii , Teruaki Kakema , Mariko Takeda
发明人： Masamichi Hashimoto , Tadashi Morikawa , Yoshiaki Miyata , Akio Ohno , Kei Takahashi , Daisuke Ogasawara , Kenji Fujii , Teruaki Kakema , Mariko Takeda
IPC分类号： A61K31/728
CPC分类号： A61K31/728 , A61K8/735 , A61K9/0019 , A61K9/0024 , A61K2800/87 , A61K2800/91 , A61Q19/08 , C08B37/0072 , C08L5/08 , Y10T428/2982
摘要： The present invention provides a crosslinked hyaluronic acid composition including self-crosslinking hyaluronic acid particles having an equilibrium swelling capacity of 3-fold to 10-fold, and an aqueous solvent, wherein a dry weight of the self-crosslinking hyaluronic acid particles based on the total volume of the crosslinked hyaluronic acid composition is 3 w/v % to 8 w/v %.The crosslinked hyaluronic acid composition of the invention uses self-crosslinking hyaluronic acid particles of which the equilibrium swelling capacity is within the above predetermined range. Accordingly, the viscosity does not sharply increase even if the concentration thereof is increased. Therefore, if the crosslinked hyaluronic acid composition is applied to an injection, it is possible to obtain a sufficient curative effect on knee osteoarthritis even with a small frequency of administration.
摘要翻译：本发明提供一种交联透明质酸组合物，其包含平衡溶胀能力为3倍至10倍的自交联透明质酸颗粒和水性溶剂，其中基于所述自交联透明质酸颗粒的干重交联透明质酸组合物的总体积为3w / v％至8w / v％。本发明的交联透明质酸组合物使用自交联透明质酸颗粒，其平衡溶胀能力在上述预定范围内。因此，即使其浓度增加，粘度也不会急剧增加。因此，如果将交联透明质酸组合物应用于注射剂，则即使施用次数较少，也可以获得对膝关节骨性关节炎的充分治疗效果。

8. 发明申请

US20070160237A1 Amplifier apparatus and acoustic system 审中-公开
标题翻译：放大器装置和声学系统
公开(公告)号：US20070160237A1
公开(公告)日：2007-07-12
申请号：US10597789
申请日：2005-02-04
申请人： Masayuki Hibino , Tadashi Morikawa
发明人： Masayuki Hibino , Tadashi Morikawa
IPC分类号： H03F21/00 , H04B1/00
CPC分类号： H04H60/04 , H03G3/3005 , H04S1/007
摘要： It is an object of the present invention to provide an amplifier apparatus which can amplify the sound signal at a relatively high quality, and to provide an acoustic system comprising the amplifier apparatus. The amplifier apparatus comprises a first amplifier 13 having a first acoustic gain, and being adapted to amplify an analog sound signal according to the first acoustic gain, and to allow the first acoustic gain to be changed, an analog-to-digital converter 14 for converting the amplified analog sound signal to a digital sound signal, a second amplifier 15 having an second acoustic gain, being adapted to amplify the digital sound signal according to the second acoustic gain, and to allow the second acoustic gain to be changed, and a controller 16 for obtaining a combined acoustic gain from the first and second acoustic gains, and keeping the combined acoustic gain constant by modifying the second acoustic gain in response to a change of the first acoustic gain.
摘要翻译：本发明的目的是提供一种能够以较高质量放大声音信号的放大器装置，并提供包括该放大器装置的声学系统。放大器装置包括具有第一声增益的第一放大器13，并且适于根据第一声增益放大模拟声音信号，并允许改变第一声增益;模数转换器14，用于将放大的模拟声音信号转换为数字声音信号，具有第二声增益的第二放大器15适于根据第二声增益放大数字声音信号，并允许改变第二声增益，以及控制器16，用于从第一和第二声增益获得组合的声增益，并且响应于第一声增益的改变，通过修改第二声增益来保持组合的声增益恒定。

9. 发明授权

US09216193B2 Crosslinked hyaluronic acid composition and self-crosslinking hyaluronic acid particles 有权
标题翻译：交联透明质酸组合物和自交联透明质酸颗粒
公开(公告)号：US09216193B2
公开(公告)日：2015-12-22
申请号：US13818848
申请日：2011-08-23
申请人： Masamichi Hashimoto , Tadashi Morikawa , Yoshiaki Miyata , Akio Ohno , Kei Takahashi , Daisuke Ogasawara , Kenji Fujii , Teruaki Kakema , Mariko Takeda
发明人： Masamichi Hashimoto , Tadashi Morikawa , Yoshiaki Miyata , Akio Ohno , Kei Takahashi , Daisuke Ogasawara , Kenji Fujii , Teruaki Kakema , Mariko Takeda
IPC分类号： A61K31/727 , A61K31/728 , C08B37/08 , C08L5/08 , A61K8/73 , A61K9/00
CPC分类号： A61K31/728 , A61K8/735 , A61K9/0019 , A61K9/0024 , A61K2800/87 , A61K2800/91 , A61Q19/08 , C08B37/0072 , C08L5/08 , Y10T428/2982
摘要： The present invention provides a crosslinked hyaluronic acid composition including self-crosslinking hyaluronic acid particles having an equilibrium swelling capacity of 3-fold to 10-fold, and an aqueous solvent, wherein a dry weight of the self-crosslinking hyaluronic acid particles based on the total volume of the crosslinked hyaluronic acid composition is 3 w/v % to 8 w/v %.The crosslinked hyaluronic acid composition of the invention uses self-crosslinking hyaluronic acid particles of which the equilibrium swelling capacity is within the above predetermined range. Accordingly, the viscosity does not sharply increase even if the concentration thereof is increased. Therefore, if the crosslinked hyaluronic acid composition is applied to an injection, it is possible to obtain a sufficient curative effect on knee osteoarthritis even with a small frequency of administration.
摘要翻译：本发明提供一种交联透明质酸组合物，其包含平衡溶胀能力为3倍至10倍的自交联透明质酸颗粒和水性溶剂，其中基于所述自交联透明质酸颗粒的干重交联透明质酸组合物的总体积为3w / v％至8w / v％。本发明的交联透明质酸组合物使用自交联透明质酸颗粒，其平衡溶胀能力在上述预定范围内。因此，即使其浓度增加，粘度也不会急剧增加。因此，如果将交联透明质酸组合物应用于注射剂，则即使施用次数较少，也可以获得对膝关节骨性关节炎的充分治疗效果。

10. 发明申请

US20070133824A1 Audio mixer 审中-公开
标题翻译：音频混音器
公开(公告)号：US20070133824A1
公开(公告)日：2007-06-14
申请号：US10597900
申请日：2005-02-04
申请人： Masayuki Hibino , Tadashi Morikawa
发明人： Masayuki Hibino , Tadashi Morikawa
IPC分类号： H03G3/00
CPC分类号： H04S7/40 , H04H60/04
摘要： It is an object of the present invention to provide an audio mixer which can specify and inform whether or not each of the audio signals exceeds a threshold level, without switching to each group. The audio mixer includes: group selecting means 3 for selecting one group from among groups having audio signals allocated thereto; level information display means 4 for displaying level information indicative of signal levels of the audio signals of the one group selected by the group selecting means 3; signal level judging means 6 for judging whether or not each of the audio signals of the groups is a larger than a threshold level; and peak information display means 7 for displaying peak information of each audio signal, the peak information being indicative of the judgment made by the signal level judging means 6.
摘要翻译：本发明的目的是提供一种音频混频器，其可以指定并通知每个音频信号是否超过阈值电平，而不切换到每个组。音频混合器包括：组选择装置3，用于从分配有音频信号的组中选择一组; 电平信息显示装置4，用于显示指示由组选择装置3选择的一组的音频信号的信号电平的电平信息; 信号电平判断装置6，用于判断组中的每个音频信号是否大于阈值电平; 和用于显示每个音频信号的峰值信息的峰值信息显示装置7，峰值信息表示由信号电平判断装置6作出的判断。

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