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1. 发明授权

US08969298B2 Liquid preparation of physiologically active peptide 有权
标题翻译：生理活性肽的液体制剂
公开(公告)号：US08969298B2
公开(公告)日：2015-03-03
申请号：US12848638
申请日：2010-08-02
申请人： Masaru Matsumoto , Masako Matsumoto , Takeshi Hanada , Naomi Wakabayashi
发明人： Masaru Matsumoto , Masako Matsumoto , Takeshi Hanada , Naomi Wakabayashi
IPC分类号： A61K38/02 , A61K9/00 , A61K38/25 , A61K47/10 , A61K47/12 , A61K47/22 , A61K47/26 , A61K47/40
CPC分类号： A61K9/0019 , A61K38/25 , A61K47/10 , A61K47/12 , A61K47/22 , A61K47/26 , A61K47/40
摘要： An effective liquid preparation achieves high bioavailability (BA) of physiologically active peptides or proteins, including ghrelins, that are administered as drugs. Also provided is a method for improving the BA of physiologically active peptides or proteins, including ghrelins, that are subcutaneously injected in aqueous solutions. The liquid preparation contains: a physiologically active peptide or protein, such as ghrelins, as an active ingredient; an acid solution including one or a combination of two or more selected form the group consisting of acetic acid, lactic acid, phosphoric acid, glycine, citric acid, hydrochloric acid, propionic acid, butyric acid, benzoic acid and salts thereof; an alcohol; and a polar organic liquid including one or a combination of two or more selected from the group consisting of N-methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide and methylparaben.
摘要翻译：有效的液体制剂实现了作为药物施用的生理活性肽或蛋白质（包括生长素释放肽）的高生物利用度（BA）。还提供了一种用于改善皮下注射在水溶液中的生理活性肽或蛋白质（包括生长素释放肽）的BA的方法。液体制剂含有：生理活性肽或蛋白质，如生长素释放肽，作为活性成分; 包括选自乙酸，乳酸，磷酸，甘氨酸，柠檬酸，盐酸，丙酸，丁酸，苯甲酸及其盐中的一种或两种以上组合的酸溶液; 酒精; 以及包含选自N-甲基-2-吡咯烷酮，二甲基甲酰胺，二甲基亚砜和对羟基苯甲酸甲酯中的一种或两种以上的组合的极性有机液体。

2. 发明授权

US07803768B2 Method for treatment of hyperglycemia in a subject in need thereof 有权
标题翻译：用于治疗有需要的受试者的高血糖症的方法
公开(公告)号：US07803768B2
公开(公告)日：2010-09-28
申请号：US11884881
申请日：2006-02-23
申请人： Kenji Kangawa , Takashi Akamizu , Taiga Irako , Shuichi Koda , Naomi Wakabayashi
发明人： Kenji Kangawa , Takashi Akamizu , Taiga Irako , Shuichi Koda , Naomi Wakabayashi
IPC分类号： A61K38/00
CPC分类号： C07K14/60 , A61K38/00
摘要： A pharmaceutical for promoting neogenesis or regeneration of pancreatic β cells which produces and secretes insulin and for promoting insulin production in β cells, comprising ghrelin or a derivative thereof as an effective component.
摘要翻译：促进胰腺新生或再生的药物产生和分泌胰岛素并促进胰岛素生产的细胞细胞，其包含生长素释放肽或其衍生物作为有效成分。

3. 发明授权

US08710184B2 Motilin-like peptide compound having transmucosal absorbability imparted thereto 有权
标题翻译：具有经粘膜吸收性的胃动素肽类化合物
公开(公告)号：US08710184B2
公开(公告)日：2014-04-29
申请号：US13388021
申请日：2010-07-29
申请人： Seiji Sato , Takeshi Hanada , Naomi Wakabayashi , Yutaka Masuda , Yuriko Harada
发明人： Seiji Sato , Takeshi Hanada , Naomi Wakabayashi , Yutaka Masuda , Yuriko Harada
IPC分类号： A61K38/16 , A61P1/04 , A61P1/00 , C07K14/00
CPC分类号： C07K14/63 , A61K38/00
摘要： The present invention aims at providing motilin-like peptide compounds that maintain the gastrointestinal motility stimulating activity of native motilin and which are adapted to have higher absorbability upon transmucosal administration. Motilin derivatives were designed and synthesized in consideration of the pathway for the degradation of motilin at a site of its transmucosal absorption and the maintenance of motilin's physiological activity and compounds characterized by substitutions for the amino acid at position 21 of native motilin have been found to show higher absorbability upon transmucosal administration and yet maintain the same activity as motilin.
摘要翻译：本发明的目的在于提供维持天然胃动素的胃肠动力刺激活性的胃动素样肽化合物，其适于在经粘膜给药时具有较高的吸收性。考虑到胃粘蛋白在其经粘膜吸收部位的降解途径和维持胃动素生理活性的途径，Motilin衍生物的设计和合成，已发现天然胃动素21位氨基酸的取代为特征的化合物经粘膜给药后的吸收能力较高，但仍维持与胃动素相同的活性。

4. 发明授权

US08551937B2 Peptide having an extending action for half-life of object peptide in plasma 有权
标题翻译：具有血浆中目标肽半衰期延长作用的肽
公开(公告)号：US08551937B2
公开(公告)日：2013-10-08
申请号：US12675961
申请日：2009-05-22
申请人： Naomi Wakabayashi , Seiji Sato
发明人： Naomi Wakabayashi , Seiji Sato
IPC分类号： A61K38/02
CPC分类号： C07K14/00 , A61K47/62 , C07K14/58 , C07K14/63 , C07K16/26 , C07K2319/31
摘要： An isolated chimeric peptide consisting of one or two added peptides and an object peptide wherein the added peptide is bonded to the N-terminus, the C-terminus or both of the object peptide, wherein if the added peptides are bound to both terminals, the two added peptides may be the same or different; and physiological activity of the object peptide is still retained, wherein the object peptide is a natural physiologically active peptide selected from the group consisting of an atrial natriuretic peptide, a brain natriuretic peptide, a C-type natriuretic peptide, motilin, a glucagon-like peptide 1, parathyroid hormone, and calcitonin, or a derivative of any thereof, wherein the derivative has one or more amino acid(s) deleted from the amino acid sequence of a natural physiologically active peptide and has the desired physiological activity.
摘要翻译：由一个或两个添加的肽和目标肽组成的分离的嵌合肽，其中所加入的肽与目标肽的N末端，C-末端或两者结合，其中如果添加的肽结合到两个末端，两个添加的肽可以相同或不同; 目标肽的生理活性仍然保留，其中，所述目标肽是天然生理活性肽，其选自心钠素利钠肽，脑利钠肽，C型利尿钠肽，胃动素，胰高血糖素样肽1，甲状旁腺激素和降钙素或其任何衍生物，其中所述衍生物具有一个或多个氨基酸，其从天然生理活性肽的氨基酸序列中缺失并具有所需的生理活性。

5. 发明申请

US20120129762A1 MOTILIN-LIKE PEPTIDE COMPOUND HAVING TRANSMUCOSAL ABSORBABILITY IMPARTED THERETO 有权
标题翻译：具有转移吸收能力的类似地胶的化合物
公开(公告)号：US20120129762A1
公开(公告)日：2012-05-24
申请号：US13388021
申请日：2010-07-29
申请人： Seiji Sato , Takeshi Hanada , Naomi Wakabayashi , Yutaka Masuda , Yuriko Harada
发明人： Seiji Sato , Takeshi Hanada , Naomi Wakabayashi , Yutaka Masuda , Yuriko Harada
IPC分类号： A61K38/16 , A61P1/04 , A61P1/00 , C07K14/00 , A61P31/04
CPC分类号： C07K14/63 , A61K38/00
摘要： The present invention aims at providing motilin-like peptide compounds that maintain the gastrointestinal motility stimulating activity of native motilin and which are adapted to have higher absorbability upon transmucosal administration.Motilin derivatives were designed and synthesized in consideration of the pathway for the degradation of motilin at a site of its transmucosal absorption and the maintenance of motilin's physiological activity and compounds characterized by substitutions for the amino acid at position 21 of native motilin have been found to show higher absorbability upon transmucosal administration and yet maintain the same activity as motilin.
摘要翻译：本发明的目的在于提供维持天然胃动素的胃肠动力刺激活性的胃动素样肽化合物，其适于在经粘膜给药时具有较高的吸收性。考虑到胃粘蛋白在其经粘膜吸收部位的降解途径和维持胃动素生理活性的途径，Motilin衍生物的设计和合成，已经发现天然胃动素21位氨基酸的取代为特征经粘膜给药后的吸收能力较强，但维持与胃动素相同的活性。

6. 发明申请

US20110077195A1 LIQUID PREPARATION OF PHYSIOLOGICALLY ACTIVE PEPTIDE 有权
标题翻译：液体制备生理活性肽
公开(公告)号：US20110077195A1
公开(公告)日：2011-03-31
申请号：US12848638
申请日：2010-08-02
申请人： Masaru Matsumoto , Masako Matsumoto , Takeshi Hanada , Naomi Wakabayashi
发明人： Masaru Matsumoto , Masako Matsumoto , Takeshi Hanada , Naomi Wakabayashi
IPC分类号： A61K38/02 , A61K38/28 , A61K38/18 , A61K38/27 , A61K38/26 , A61K38/29 , A61K38/22
CPC分类号： A61K9/0019 , A61K38/25 , A61K47/10 , A61K47/12 , A61K47/22 , A61K47/26 , A61K47/40
摘要： An effective liquid preparation achieves high bioavailability (BA) of physiologically active peptides or proteins, including ghrelins, that are administered as drugs. Also provided is a method for improving the BA of physiologically active peptides or proteins, including ghrelins, that are subcutaneously injected in aqueous solutions. The liquid preparation contains: a physiologically active peptide or protein, such as ghrelins, as an active ingredient; an acid solution including one or a combination of two or more selected form the group consisting of acetic acid, lactic acid, phosphoric acid, glycine, citric acid, hydrochloric acid, propionic acid, butyric acid, benzoic acid and salts thereof; an alcohol; and a polar organic liquid including one or a combination of two or more selected from the group consisting of N-methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide and methylparaben.
摘要翻译：有效的液体制剂实现了作为药物施用的生理活性肽或蛋白质（包括生长素释放肽）的高生物利用度（BA）。还提供了一种用于改善皮下注射在水溶液中的生理活性肽或蛋白质（包括生长素释放肽）的BA的方法。液体制剂含有：生理活性肽或蛋白质，如生长素释放肽，作为活性成分; 包括选自乙酸，乳酸，磷酸，甘氨酸，柠檬酸，盐酸，丙酸，丁酸，苯甲酸及其盐中的一种或两种以上组合的酸溶液; 酒精; 以及包含选自N-甲基-2-吡咯烷酮，二甲基甲酰胺，二甲基亚砜和对羟基苯甲酸甲酯中的一种或两种以上的组合的极性有机液体。

7. 发明申请

US20090143284A1 Promoter of Regeneration of Pancreatic B Cell, and Promoter of Insulin Production in Pancreatic B Cell 有权
标题翻译：胰腺B细胞再生的启动子和胰岛素B细胞胰岛素的启动子
公开(公告)号：US20090143284A1
公开(公告)日：2009-06-04
申请号：US11884881
申请日：2006-02-23
申请人： Kenji Kangawa , Takashi Akamizu , Taiga Irako , Shuichi Koda , Naomi Wakabayashi
发明人： Kenji Kangawa , Takashi Akamizu , Taiga Irako , Shuichi Koda , Naomi Wakabayashi
IPC分类号： A61K38/17 , A61P7/00
CPC分类号： C07K14/60 , A61K38/00
摘要： A pharmaceutical for promoting neogenesis or regeneration of pancreatic β cells which produces and secretes insulin and for promoting insulin production in β cells, comprising ghrelin or a derivative thereof as an effective component.
摘要翻译：一种用于促进胰腺β细胞的新生或再生的药物，其产生和分泌胰岛素并促进β细胞中的胰岛素产生，其包括生长素释放肽或其衍生物作为有效成分。

8. 发明申请

US20080193997A1 Liquid Preparation of Physiologically Active Peptide 审中-公开
标题翻译：液体制备生理活性肽
公开(公告)号：US20080193997A1
公开(公告)日：2008-08-14
申请号：US11660406
申请日：2005-08-24
申请人： Masaru Matsumoto , Masako Matsumoto , Takeshi Hanada , Naomi Wakabayashi
发明人： Masaru Matsumoto , Masako Matsumoto , Takeshi Hanada , Naomi Wakabayashi
IPC分类号： C12N9/94
CPC分类号： A61K9/0019 , A61K38/25 , A61K47/10 , A61K47/12 , A61K47/22 , A61K47/26 , A61K47/40
摘要： An effective liquid preparation achieves high bioavailability (BA) of physiologically active peptides or proteins, including ghrelins, that are administered as drugs. Also provided is a method for improving the BA of physiologically active peptides or proteins, including ghrelins, that are subcutaneously injected in aqueous solutions. The liquid preparation contains: a physiologically active peptide or protein, such as ghrelins, as an active ingredient; an acid solution including one or a combination of two or more selected form the group consisting of acetic acid, lactic acid, phosphoric acid, glycine, citric acid, hydrochloric acid, propionic acid, butyric acid, benzoic acid and salts thereof; an alcohol; and a polar organic liquid including one or a combination of two or more selected from the group consisting of N-methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide and methylparaben.
摘要翻译：有效的液体制剂实现了作为药物施用的生理活性肽或蛋白质（包括生长素释放肽）的高生物利用度（BA）。还提供了一种用于改善皮下注射在水溶液中的生理活性肽或蛋白质（包括生长素释放肽）的BA的方法。液体制剂含有：生理活性肽或蛋白质，如生长素释放肽，作为活性成分; 包括选自乙酸，乳酸，磷酸，甘氨酸，柠檬酸，盐酸，丙酸，丁酸，苯甲酸及其盐中的一种或两种以上组合的酸溶液; 酒精; 以及包含选自N-甲基-2-吡咯烷酮，二甲基甲酰胺，二甲基亚砜和对羟基苯甲酸甲酯中的一种或两种以上的组合的极性有机液体。

9. 发明申请

US20100305031A1 PEPTIDE HAVING AN EXTENDING ACTION FOR HALF-LIFE OF OBJECT PEPTIDE IN PLASMA 有权
标题翻译：具有等离子体对象肽半衰期的延伸作用的肽
公开(公告)号：US20100305031A1
公开(公告)日：2010-12-02
申请号：US12675961
申请日：2009-05-22
申请人： Naomi Wakabayashi , Sato Seiji
发明人： Naomi Wakabayashi , Sato Seiji
IPC分类号： A61K38/08 , C07K7/06 , C07K7/08 , C07K14/00 , C07K14/435 , A61K38/10 , A61K38/16 , A61P9/00 , A61P19/02 , A61P3/10
CPC分类号： C07K14/00 , A61K47/62 , C07K14/58 , C07K14/63 , C07K16/26 , C07K2319/31
摘要： A peptide of the following (I) or (II). (I) a peptide represented by the formula B, A-B, B-C or A-B-C in which A, B and C each is represented by the following (1), (2) and (3) and, when it is bonded to other object peptide, it is able to extent the half-life in plasma as compared with the object peptide where the physiological activity of the object peptide is still retained. (II) a peptide comprising a reversed sequence of the peptide of (I); a sequence which is represented by A-B in (I) and A or B is reversed; a sequence which is represented by B-C in (I) and B or C is reversed; or a sequence which is represented by A-B-C in (I) and A, B, C, A and B, B and C or A and C is reserved. (1) A is a peptide comprising 1 to 14 of any amino acid(s) (2) B is a peptide represented by the formula 1: (Wk-Xl-Y-Zm-Wn)-(Wo-Xp-Y-Zq-Wr)s (In the formula 1, W is a basic amino acid; X and Z are any amino acids; Y is an acidic amino acid; k is 1 or 2; l is an integer of 4≧l≧0; m is an integer of 2≧m≧0; 4≧l+m≧0; n is 1 or 2; o is 1 or 2; p is an integer of 4≧p≧0; q is an integer of 2≧q≧0; 4≧p+q≧0; r is 1 or 2; and s is 0 or 1.) (3) C is a peptide comprising 2 to 14 of any amino acids.
摘要翻译：下列（I）或（II）的肽。（I）由式B，AB，BC或ABC表示的肽，其中A，B和C各自由以下（1），（2）和（3）表示，并且当其结合到其它目标肽与目标肽的生理活性仍然保留的目标肽相比，能够调节血浆中的半衰期。（II）包含（I）的肽的逆序列的肽; （I）和A或B中的A-B表示的序列相反; 由（I）中的B-C和B或C表示的序列相反; 或由A，B，C，A和B，B和C或A和C中的A-B-C表示的序列被保留。（1）A是包含1至14个任意氨基酸的肽（2）B是由式1表示的肽：（Wk-X1-Y-Zm-Wn） - （Wo-Xp-Y- Zq-Wr）s（式1中，W为碱性氨基酸，X为Z为任意氨基酸，Y为酸性氨基酸，k为1或2，l为4≥1≥0的整数。 m是2≥m≥0的整数;4≥1+m≥0; n是1或2; o是1或2; p是4≥P≥0的整数; q是2≥q的整数 ≥0;4≥p+q≥0; r为1或2; s为0或1.）（3）C为任意氨基酸2〜14个的肽。

10. 发明申请

US20090233851A1 Insulin Resistance Improver 审中-公开
标题翻译：胰岛素抵抗改善剂
公开(公告)号：US20090233851A1
公开(公告)日：2009-09-17
申请号：US11921027
申请日：2006-05-26
申请人： Naomi Wakabayashi , Yuriko Harada , Yutaka Masuda
发明人： Naomi Wakabayashi , Yuriko Harada , Yutaka Masuda
IPC分类号： A61K38/22
CPC分类号： A61K9/0043 , A61K9/0019 , A61K9/0073 , A61K38/26
摘要： A novel dosage regimen of GLP-1 receptor agonists causes little or no side effects or drug interactions and is suitable for improving insulin resistance. Also provided is an insulin resistance improver for use in the dosage regimen. The dosage regimen comprises repeatedly administering, preferably in a non-invasive manner, a GLP-1 receptor agonist at least before eating for a predetermined period of time to create a condition similar to what is observed with postprandial temporary secretion of the endogenous GLP-1 receptor agonist, rather than administering it continuously. This creates a similar or enhanced variation in the plasma levels of GLP-1 receptor agonist as compared to the circadian variation of the endogenous GLP-1 receptor agonist in a healthy individual. A pharmaceutical composition for use in the dosage regimen containing GLP-1 receptor agonist as an active ingredient is also provided.
摘要翻译： GLP-1受体激动剂的新型剂量方案很少或没有副作用或药物相互作用，并且适合于改善胰岛素抵抗。还提供了用于剂量方案的胰岛素抵抗改善剂。所述给药方案包括至少在进食预定时间段之前重复施用GLP-1受体激动剂，优选以非侵入性方式施用GLP-1受体激动剂以产生类似于用餐后临时分泌内源性GLP-1 受体激动剂，而不是连续施用它。与健康个体内源性GLP-1受体激动剂的昼夜变化相比，这产生了与GLP-1受体激动剂血浆水平相似或增强的变化。还提供了用于含有GLP-1受体激动剂作为活性成分的给药方案中的药物组合物。

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