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1. 发明申请

US20110086106A1 METHOD OF PRODUCING A DRY EARTHWORM POWDER 有权
标题翻译：生产干土粉的方法
公开(公告)号：US20110086106A1
公开(公告)日：2011-04-14
申请号：US12903615
申请日：2010-10-13
申请人： Yoichi ISHII , Kazuyuki Ishii , Hiroyuki Sumi , Etsuo Yoshida , Sayaka Ishii
发明人： Yoichi ISHII , Kazuyuki Ishii , Hiroyuki Sumi , Etsuo Yoshida , Sayaka Ishii
IPC分类号： A61K35/56
CPC分类号： A61K35/62
摘要： Provided is a simple and easy method of producing an innoxious dry earthworm powder, while suppressing inactivation of the enzymes contained in earthworms. In the method, a homogenate obtained by grinding living earthworms is freeze-dried and the dried product is heat-treated at a temperature of 110° C. or higher but lower than 130° C. Preferably, the method according to the present invention comprises further a process for preparation of the living earthworms, which precedes the grinding step, comprising the steps of: standing the living earthworms under light for 10 to 50 hours; removing the dirt formed on the skin thereof, bringing the earthworms into contact with an organic acid for 30 seconds or less; diluting the acid with addition of water to adjust the pH of the aqueous acidic solution to a pH in the range of 2 to 5; standing the earthworm mixture under the pH condition for 3 to 180 minutes; and then washing the earthworms with water.
摘要翻译：提供了一种简单易行的生产无嗅干蚯蚓粉的方法，同时抑制蚯蚓中含有的酶的失活。在该方法中，通过研磨活蚯蚓获得的匀浆物被冷冻干燥，干燥产物在110℃以上且低于130℃的温度下进行热处理。优选地，根据本发明的方法包括进一步的在研磨步骤之前制备活蚯蚓的方法，包括以下步骤：将活蚯蚓放在灯下10-50小时; 除去形成在其皮肤上的污垢，使蚯蚓与有机酸接触30秒以下; 通过添加水稀释酸，以将酸性水溶液的pH调节至2至5范围内的pH; 在pH条件下静置蚯蚓混合物3〜180分钟; 然后用水洗蚯蚓。

2. 发明授权

US08394417B2 Method of producing a dry earthworm powder 有权
标题翻译：生产干蚯蚓粉的方法
公开(公告)号：US08394417B2
公开(公告)日：2013-03-12
申请号：US12903615
申请日：2010-10-13
申请人： Yoichi Ishii , Kazuyuki Ishii , Hiroyuki Sumi , Etsuo Yoshida , Sayaka Ishii
发明人： Yoichi Ishii , Kazuyuki Ishii , Hiroyuki Sumi , Etsuo Yoshida , Sayaka Ishii
IPC分类号： A61K35/56
CPC分类号： A61K35/62
摘要： Provided is a simple and easy method of producing an innoxious dry earthworm powder, while suppressing inactivation of the enzymes contained in earthworms. In the method, a homogenate obtained by grinding living earthworms is freeze-dried and the dried product is heat-treated at a temperature of 110° C. or higher but lower than 130° C. Preferably, the method according to the present invention comprises further a process for preparation of the living earthworms, which precedes the grinding step, comprising the steps of: standing the living earthworms under light for 10 to 50 hours; removing the dirt formed on the skin thereof, bringing the earthworms into contact with an organic acid for 30 seconds or less; diluting the acid with addition of water to adjust the pH of the aqueous acidic solution to a pH in the range of 2 to 5; standing the earthworm mixture under the pH condition for 3 to 180 minutes; and then washing the earthworms with water.
摘要翻译：提供了一种简单易行的生产无嗅干蚯蚓粉的方法，同时抑制蚯蚓中含有的酶的失活。在该方法中，通过研磨活蚯蚓获得的匀浆物被冷冻干燥，干燥产物在110℃以上且低于130℃的温度下进行热处理。优选地，根据本发明的方法包括进一步的在研磨步骤之前制备活蚯蚓的方法，包括以下步骤：将活蚯蚓放在灯下10-50小时; 除去形成在其皮肤上的污垢，使蚯蚓与有机酸接触30秒以下; 通过添加水稀释酸，以将酸性水溶液的pH调节至2至5范围内的pH; 在pH条件下静置蚯蚓混合物3〜180分钟; 然后用水洗蚯蚓。

3. 发明申请

US20140154331A1 TYROSINASE INHIBITOR PRODUCED USING DRIED EARTHWORM POWDER, AND METHOD FOR PRODUCING SAME 有权
标题翻译：使用干地泥粉生产的酪氨酸酶抑制剂及其生产方法
公开(公告)号：US20140154331A1
公开(公告)日：2014-06-05
申请号：US14235191
申请日：2012-07-24
申请人： Yoichi Ishii , Kazuyuki Ishii
发明人： Yoichi Ishii , Kazuyuki Ishii
IPC分类号： A61K8/98
CPC分类号： A61K8/98 , A61K8/022 , A61K8/987 , A61K35/62 , A61Q19/00 , A61Q19/02
摘要： The present invention provides a highly safe tyrosinase inhibitor having excellent tyrosinase-inhibiting action, and a method for producing the tyrosinase inhibitor. The method for producing a tyrosinase inhibitor comprises the steps of contacting a live earthworm with hydroxycarboxylic acid powder, diluting the resulting mixture with water to adjust the pH to 2 to 5, and then leaving the resulting dilution to stand for 3 to 180 minutes, or contacting a live earthworm with an aqueous solution of hydroxycarboxylic acid having a pH of 2 to 5 and then leaving the resulting mixture to stand for 3 to 180 minutes; followed by washing the live earthworm with water, grinding the washed earthworm, and then freeze-drying the obtained ground product.
摘要翻译：本发明提供了具有优异的酪氨酸酶抑制作用的高度安全的酪氨酸酶抑制剂，以及制备酪氨酸酶抑制剂的方法。制备酪氨酸酶抑制剂的方法包括以下步骤：将活蚯蚓与羟基羧酸粉末接触，将所得混合物用水稀释以将pH调节至2至5，然后将所得稀释液静置3至180分钟，或使活蚯蚓与pH为2至5的羟基羧酸水溶液接触，然后将所得混合物静置3至180分钟; 然后用水清洗活蚯蚓，研磨洗涤的蚯蚓，然后冷冻干燥所得的研磨产物。

4. 发明授权

US09060958B2 Tyrosinase inhibitor produced using dried earthworm powder, and method for producing same 有权
标题翻译：使用干蚯蚓粉制备的酪氨酸酶抑制剂及其制备方法
公开(公告)号：US09060958B2
公开(公告)日：2015-06-23
申请号：US14235191
申请日：2012-07-24
申请人： Yoichi Ishii , Kazuyuki Ishii
发明人： Yoichi Ishii , Kazuyuki Ishii
IPC分类号： A61K36/62 , A61K8/98 , A61Q19/02 , A61Q19/00 , A61K8/02 , A61K35/62
CPC分类号： A61K8/98 , A61K8/022 , A61K8/987 , A61K35/62 , A61Q19/00 , A61Q19/02
摘要： The present invention provides a highly safe tyrosinase inhibitor having excellent tyrosinase-inhibiting action, and a method for producing the tyrosinase inhibitor. The method for producing a tyrosinase inhibitor comprises the steps of contacting a live earthworm with hydroxycarboxylic acid powder, diluting the resulting mixture with water to adjust the pH to 2 to 5, and then leaving the resulting dilution to stand for 3 to 180 minutes, or contacting a live earthworm with an aqueous solution of hydroxycarboxylic acid having a pH of 2 to 5 and then leaving the resulting mixture to stand for 3 to 180 minutes; followed by washing the live earthworm with water, grinding the washed earthworm, and then freeze-drying the obtained ground product.
摘要翻译：本发明提供了具有优异的酪氨酸酶抑制作用的高度安全的酪氨酸酶抑制剂，以及制备酪氨酸酶抑制剂的方法。制备酪氨酸酶抑制剂的方法包括以下步骤：将活蚯蚓与羟基羧酸粉末接触，将所得混合物用水稀释以将pH调节至2至5，然后将所得稀释液静置3至180分钟，或使活蚯蚓与pH为2至5的羟基羧酸水溶液接触，然后将所得混合物静置3至180分钟; 然后用水清洗活蚯蚓，研磨洗涤的蚯蚓，然后冷冻干燥所得的研磨产物。

5. 发明申请

US20120178905A1 PROCESS FOR PRODUCTION OF PEPTIDE THIOESTER 有权
标题翻译：生产肽硫肽的方法
公开(公告)号：US20120178905A1
公开(公告)日：2012-07-12
申请号：US13379832
申请日：2010-06-21
申请人： Yasuhiro Kajihara , Ryo Okamoto , Izumi Sakamoto , Kazuyuki Ishii
发明人： Yasuhiro Kajihara , Ryo Okamoto , Izumi Sakamoto , Kazuyuki Ishii
IPC分类号： C07K1/113
CPC分类号： C07K1/1077 , C07K1/1072
摘要： A process for chemically converting a peptide chain into a peptide thioester includes, when a —C(═X)—R1 group is introduced to the thiol group of the cysteine residue and then the resulting peptide is reacted with a compound having a leaving group represented by the formula: —NH—C(═Y)NHR3 in an organic solvent, the —NH—C(═Y)NHR3 group binds via addition reaction to the carboxyl group of the N-terminal-side peptide bond of the cysteine residue, whereby the peptide bond is cleaved and the C-terminal-side peptide fragment is cut off. Further, when the resulting peptide chain having the —NH—C(═Y)NHR3 group is reacted with a thiol in a buffer solution, a thiol exchange reaction occurs, namely, the thiol group of the thiol binds to the carbonyl carbon to which the —NH—C(═Y)NHR3 group has bound, whereby the —NH—C(═Y)NHR3 group is eliminated.
摘要翻译：将肽链化学转化为肽硫酯的方法包括当将-C（= X）-R1基团引入半胱氨酸残基的硫醇基团时，然后将所得肽与具有离去基团的化合物反应通过-NH-C（= Y）NHR 3在有机溶剂中，-NH-C（= Y）NHR 3基团通过加成反应与半胱氨酸残基的N-末端侧肽键的羧基结合，由此肽键被切割并且C末端侧肽片段被切断。此外，当所得的具有-NH-C（= Y）NHR 3基团的肽链与缓冲溶液中的硫醇反应时，发生巯基交换反应，即硫醇的硫醇基与羰基碳结合， -NH-C（= Y）NHR 3基团结合，从而消除-NH-C（= Y）NHR 3基团。

6. 发明授权

US09455054B2 Radioactive cesium adsorbent, method for producing the same, and method for removing radioactive cesium in environment with said adsorbent 有权
标题翻译：放射性铯吸附剂，其制造方法，以及利用所述吸附剂在环境中除去放射性铯的方法
公开(公告)号：US09455054B2
公开(公告)日：2016-09-27
申请号：US14239736
申请日：2012-08-16
申请人： Kazuyuki Ishii , Masashi Obi , Kazuaki Kudo , Kengo Akagawa , Tetsu Tatsuma , Akiyoshi Sakoda
发明人： Kazuyuki Ishii , Masashi Obi , Kazuaki Kudo , Kengo Akagawa , Tetsu Tatsuma , Akiyoshi Sakoda
IPC分类号： G21F9/12 , G21F9/30 , B01J20/26 , B01J20/24 , B01J20/02 , B01J20/22 , B01J20/28 , B01J20/30 , B01J20/32
CPC分类号： G21F9/301 , B01J20/0229 , B01J20/24 , B01J20/26 , B01J20/28023 , B01J20/28038 , B01J20/28052 , B01J20/3078 , B01J20/3085 , B01J20/3208 , B01J20/3236 , G21F9/12 , G21F9/302
摘要： The present invention relates to a radioactive cesium adsorbent, a method for producing the same, and a method for decontaminating the environment from radioactive cesium with the adsorbent. The radioactive cesium adsorbent of the present invention includes a hydrophilic fiber substrate supporting a Prussian blue analog, in particular, Prussian blue, and the Prussian blue analog is immobilized in the inside of the fibers.
摘要翻译：本发明涉及一种放射性铯吸附剂，其制备方法，以及一种利用吸附剂从放射性铯中除去环境的方法。本发明的放射性铯吸附剂包括支持普鲁士蓝类似物，特别是普鲁士蓝的亲水性纤维基质，普鲁士蓝类似物固定在纤维的内部。

7. 发明申请

US20140336116A1 Glycosylated Polypeptide and Drug Composition Containing Said Polypeptide 有权
标题翻译：糖基化多肽和含有所述多肽的药物组合物
公开(公告)号：US20140336116A1
公开(公告)日：2014-11-13
申请号：US14342359
申请日：2012-09-03
申请人： Hirofumi Ochiai , Taiji Shimoda , Kazuhiro Fukae , Masatoshi Maeda , Kazuyuki Ishii , Kenta Yoshida , Katsunari Tezuka , Keisuke Tazuru
发明人： Hirofumi Ochiai , Taiji Shimoda , Kazuhiro Fukae , Masatoshi Maeda , Kazuyuki Ishii , Kenta Yoshida , Katsunari Tezuka , Keisuke Tazuru
IPC分类号： C07K14/655
CPC分类号： A61K47/64 , A61K38/00 , A61K47/549 , C07K14/6555
摘要： [Problem] To provide a glycosylated polypeptide having an affinity to somatostatin receptors, and, compared to somatostatins, having improved in-blood stability. [Solution] The glycosylated polypeptide is characterized by at least one amino acid in a somatostatin or an analog thereof being replaced with a glycosylated amino acid.
摘要翻译：提供对生长抑素受体具有亲和力的糖基化多肽，以及与促生长激素抑制素相比具有改善的血液内稳定性。 [溶液]糖基化多肽的特征在于生长抑素中的至少一个氨基酸或其类似物被糖基化的氨基酸替代。

8. 发明授权

US08765669B2 Glycosylated GLP-1 peptide 有权
标题翻译：糖基化GLP-1肽
公开(公告)号：US08765669B2
公开(公告)日：2014-07-01
申请号：US12999654
申请日：2009-06-15
申请人： Yasuhiro Kajihara , Takashi Tsuji , Izumi Sakamoto , Yuri Nambu , Naohiro Hayashi , Kazuyuki Ishii , Kazuhiro Fukae , Katsunari Tezuka , Hiroaki Asai
发明人： Yasuhiro Kajihara , Takashi Tsuji , Izumi Sakamoto , Yuri Nambu , Naohiro Hayashi , Kazuyuki Ishii , Kazuhiro Fukae , Katsunari Tezuka , Hiroaki Asai
IPC分类号： A61K38/26 , A61P3/10 , A61P7/12 , C07K14/605 , C07K1/00 , C07K14/00 , C07K17/00
CPC分类号： C07K14/605 , A61K38/00
摘要： Oligosaccharide chain added GLP-1 peptides are more stable in blood and more active in controlling blood-sugar levels than GLP-1 peptides without added oligosaccharides. Oligosaccharide chain added GLP-1 peptides having GLP-1 activity include at least one or at least two amino acids each substituted with an oligosaccharide chain added amino acid in GLP-1; a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or a GLP-1 analog. Oligosaccharide chain added GLP-1 peptides with at least one amino acid substituted with an oligosaccharide chain added amino acid include an oligosaccharide chain with oligo hyaluronic acid. Oligosaccharide chain added amino acids include oligosaccharide chains attached to amino acids via linkers.
摘要翻译：添加糖链的GLP-1肽在血液中更稳定，并且在没有添加低聚糖的情况下比GLP-1肽更有效地控制血糖水平。具有GLP-1活性的添加糖链的GLP-1肽包括GLP-1中由糖链连接的氨基酸取代的至少一个或至少两个氨基酸; 具有GLP-1的氨基酸序列的肽，其具有缺失，取代或添加一个或几个氨基酸; 或GLP-1类似物。具有至少一个被寡糖链添加的氨基酸取代的氨基酸的添加糖链的GLP-1肽包括具有寡聚透明质酸的寡糖链。寡糖链添加的氨基酸包括通过接头连接到氨基酸的寡糖链。

9. 发明申请

US20140058062A1 Method for Producing Glycopeptide Having Sialyl Sugar Chain, Sialyl Sugar Chain-Added Amino Acid Derivative to be Used in Same, and Glycopeptide 有权
标题翻译：具有唾液酸糖链的糖肽，用于同时使用的唾液酸糖链氨基酸衍生物和糖肽的方法
公开(公告)号：US20140058062A1
公开(公告)日：2014-02-27
申请号：US14004122
申请日：2012-03-05
申请人： Yasuhiro Kajihara , Masumi Murakami , Kazuyuki Ishii
发明人： Yasuhiro Kajihara , Masumi Murakami , Kazuyuki Ishii
IPC分类号： C07K14/00
CPC分类号： C07K14/001 , C07H1/00 , C07K1/006 , C07K1/068
摘要： [Technical Promblem]To provide a method for manufacturing that enables to obtain a targeted glycopeptide harboring a sialyl sugar chain in high yield without decomposing sialic acid at a non-reducing terminal of sugar chain when the glycopeptide is synthesized by a Boc solid phase synthesis method.[Solution to Problem]The present invention is characterized in that the Boc-sialylglycosylated amino acid derivative used in Boc solid phase synthesis method is one where the carboxyl group of the sialic acid at the sugar chain non-reducing terminal is protected with a phenacyl group.
摘要翻译： [技术要点]提供一种制造方法，其能够通过Boc固相合成法合成糖肽，能够以高产率获得含有唾液酸糖链的靶糖蛋白，而不会在糖链的非还原末端分解唾液酸。 [问题的解决方案]本发明的特征在于Boc固相合成法中使用的Boc-唾液酸糖基化氨基酸衍生物，其中在糖链非还原末端的唾液酸的羧基被苯甲酰基保护。

10. 发明授权

US09511098B2 Method for producing dry earthworm powder 有权
标题翻译：干蚯蚓粉生产方法
公开(公告)号：US09511098B2
公开(公告)日：2016-12-06
申请号：US13519346
申请日：2011-10-05
申请人： Kazuyuki Ishii
发明人： Kazuyuki Ishii
IPC分类号： A61K35/24 , A61K35/37 , A61K35/12 , A61K35/62
CPC分类号： A61K35/62
摘要： A method for producing dry earthworm powder, by which dry earthworm powder having high-titer enzymes can be produced while removing toxic substances contained in the bodies of earthworms, is provided. The method comprises: contacting a live earthworm with a chloride(s) of at least one metal selected from the group consisting of potassium, sodium, magnesium and calcium; and subsequently contacting the live earthworm with powder of a hydroxycarboxylic acid(s) and diluting the resulting mixture with water to adjust pH to 2 to 5, followed by leaving the live earthworm to stand for 3 to 180 minutes, washing the live earthworm with water, grinding the washed live earthworm and freeze-drying the obtained ground product.

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