公开(公告)号：US08895503B2

公开(公告)日：2014-11-25

申请号：US12867701

申请日：2009-02-27

申请人： Mariko Morishita ,  Kozo Takayama ,  Reiji Nishio ,  Nobuo Ida

发明人： Mariko Morishita ,  Kozo Takayama ,  Reiji Nishio ,  Nobuo Ida

IPC分类号： A61K38/19 ,  A61K38/28 ,  A61K38/00 ,  A61K38/21 ,  C07K14/435 ,  A61K38/10 ,  A61K9/00 ,  A61K47/42

CPC分类号： A61K38/215 ,  A61K9/0043 ,  A61K38/10 ,  A61K38/28 ,  A61K47/42 ,  C07K14/43581 ,  A61K2300/00

摘要： A method for nasal administration of a pharmaceutical composition comprising a hydrophilic bioactive substance and any one of (a) to (c): (a) a peptide having the amino acid sequence shown in SEQ ID NO:1; (b) a peptide having the same amino acid sequence as shown in SEQ ID NO:1 except that one or several amino acids are deleted, substituted and/or added, the peptide having nasal mucosal permeability; (c) a peptide having an amino acid sequence represented by the reverse sequence of (a) or (b), the peptide having nasal mucosal permeability, with the proviso that a C-terminal amidated peptide is excluded. A hydrophilic bioactive substance having a low transmucosal absorption capability which has conventionally been able to be administered by only injection can be nasally administered. Such a pharmaceutical composition is useful for improvement of the pain and the inconvenience of patients caused by administration by injection.

摘要翻译： 包含亲水生物活性物质和（a）至（c）中任一项的药物组合物的鼻内给药方法：（a）具有SEQ ID NO：1所示氨基酸序列的肽; （b）具有与SEQ ID NO：1所示相同氨基酸序列的肽，除了一个或多个氨基酸被缺失，取代和/或加入，具有鼻粘膜通透性的肽; （c）具有由（a）或（b）的相反序列表示的氨基酸序列的肽，所述肽具有鼻粘膜通透性，条件是排除C末端酰胺化肽。 通常只能通过注射给药的具有低透粘膜吸收能力的亲水性生物活性物质可以鼻腔给药。 这种药物组合物可用于改善由注射给药引起的患者的疼痛和不便。

公开(公告)号：US5164416A

公开(公告)日：1992-11-17

申请号：US700046

申请日：1991-05-08

申请人： Tsuneji Nagai ,  Kozo Takayama ,  Hideaki Okabe

发明人： Tsuneji Nagai ,  Kozo Takayama ,  Hideaki Okabe

IPC分类号： A61K31/19 ,  A61K31/405 ,  A61K31/415 ,  A61K31/515 ,  A61K31/60 ,  A61K47/06

CPC分类号： A61K31/415 ,  A61K31/19 ,  A61K31/405 ,  A61K31/515 ,  A61K31/60 ,  A61K47/06 ,  A61K9/0014 ,  Y10S514/817 ,  Y10S514/947

摘要： A transdermal therapeutic formulation comprising d-limonene and at least one pharmaceutically active substance wherein the content of the d-limonene is in the range from 0.1 to 2 weight percent, based on the total amount of the formulation. The transdermal therapeutic formulation has an excellent percutaneous absorption, is safe and is capable of delivering desired pharmaceutically active substances to a desired location of treatment or to the entire body of a patient through the circulatory system and is thus effective for curing various diseases.

摘要翻译： 一种透皮治疗剂，其包含d-柠檬烯和至少一种药物活性物质，其中所述d-柠檬烯的含量基于所述制剂的总量为0.1至2重量％。 透皮治疗制剂具有优异的经皮吸收，是安全的，并且能够通过循环系统将期望的药物活性物质递送到患者的期望的治疗位置或整个身体，因此有效地治愈各种疾病。

公开(公告)号：US20120065124A1

公开(公告)日：2012-03-15

申请号：US13321176

申请日：2010-05-19

申请人： Mariko Morishita ,  Kozo Takayama ,  Reiji Nishio ,  Nobuo Ida

发明人： Mariko Morishita ,  Kozo Takayama ,  Reiji Nishio ,  Nobuo Ida

IPC分类号： A61K38/02 ,  A61K47/42 ,  A61K31/7088 ,  C07K7/08 ,  C07K7/06

CPC分类号： C07K7/08 ,  A61K9/0053 ,  A61K9/007 ,  A61K9/0073 ,  A61K38/10 ,  C07K14/43581

摘要： A cell-penetrating peptide of (A) to (D) below gives cell membrane permeability and transmucosal absorbability to a physiologically active substance: (A) a peptide having the amino acid sequence of SEQ ID NO:1; (B) a peptide represented by SEQ ID NO:1 except that one or several basic amino acids are changed; (C) a peptide represented by SEQ ID NO:1 except that 1 to 5 amino acids are changed; (D) a peptide having: the reverse sequence of any of (A) to (C); an amino acid sequence which is the same as the reverse sequence of (A) except that one or several basic amino acids are changed; or an amino acid sequence which is the same as the reverse sequence of (A) except that 1 to 5 amino acids are changed.

摘要翻译： （A）〜（D）的细胞穿透肽赋予生理活性物质的细胞膜通透性和经粘膜吸收性：（A）具有SEQ ID NO：1的氨基酸序列的肽; （B）除了一个或几个碱性氨基酸改变之外，由SEQ ID NO：1表示的肽; （C）除了1〜5个氨基酸改变之外，由SEQ ID NO：1表示的肽; （D）具有（A）至（C）中任一个的相反序列的肽; 与（A）的相反序列相同的氨基酸序列，除了一个或多个碱性氨基酸改变; 或与（A）的相反序列相同的氨基酸序列，只是改变1至5个氨基酸。

公开(公告)号：US20110151001A1

公开(公告)日：2011-06-23

申请号：US12991134

申请日：2009-03-03

申请人： Yasuko Obata ,  Yuki Otake ,  Kozo Takayama

发明人： Yasuko Obata ,  Yuki Otake ,  Kozo Takayama

IPC分类号： A61K9/00 ,  A61K31/5415 ,  A61P1/08

CPC分类号： A61K9/0014 ,  A61K9/7053 ,  A61K9/7061 ,  A61K9/7069 ,  A61K9/7076 ,  A61K31/5415 ,  A61K47/10

摘要： Disclosed is a novel pharmaceutical composition for external application for increasing the permeation of prochlorperazine or a pharmaceutically acceptable salt thereof through the skin to allow prochlorperazine or the pharmaceutically acceptable salt thereof to exhibit its excellent pharmacological activity. Specifically disclosed is a novel pharmaceutical composition for external application, which contains prochlorperazine or a pharmaceutically acceptable salt thereof as an active ingredient and further contains menthol. The composition contains, as an active ingredient, prochlorperazine which has been widely used clinically as the first-line drug of a therapeutic agent for nausea or vomiting before or after a surgery or the like, and is extremely highly useful as a transdermally absorbable antiemetic agent that has excellent efficacy and can be used safely over a long period.

摘要翻译： 公开了用于增加丙氯拉嗪或其药学上可接受的盐通过皮肤的渗透的外用的新型药物组合物，以允许原氯丙嗪或其药学上可接受的盐显示其优异的药理活性。 具体公开了一种外用的新型药物组合物，其含有作为活性成分的丙氯拉嗪或其药学上可接受的盐，并且还含有薄荷醇。 该组合物作为活性成分含有在手术等之前或之后临床广泛用作恶心或呕吐治疗剂的一线药物的原氯丙嗪，作为透皮吸收性止吐剂非常有用 具有优异的疗效，可长期安全使用。

公开(公告)号：US20110020280A1

公开(公告)日：2011-01-27

申请号：US12867701

申请日：2009-02-27

申请人： Mariko Morishita ,  Kozo Takayama ,  Reiji Nishio ,  Nobuo Ida

发明人： Mariko Morishita ,  Kozo Takayama ,  Reiji Nishio ,  Nobuo Ida

IPC分类号： A61K38/21 ,  A61K38/10 ,  A61K38/28 ,  A61P43/00

CPC分类号： A61K38/215 ,  A61K9/0043 ,  A61K38/10 ,  A61K38/28 ,  A61K47/42 ,  C07K14/43581 ,  A61K2300/00

摘要： By a pharmaceutical composition for nasal administration comprising a hydrophilic bioactive substance and any one of (a) to (c) below, with the proviso that a C-terminal amidated peptide is excluded, a hydrophilic bioactive substance having a low transmucosal absorption capability which has conventionally been able to be administered by only injection can be nasally administered. Such a pharmaceutical composition is useful for improvement of the pain and the inconvenience of patients caused by administration by injection. (a) A peptide having the amino acid sequence shown in SEQ ID NO:1. (b) A peptide having the same amino acid sequence as shown in SEQ ID NO:1 except that one or several amino acids are deleted, substituted and/or added, the peptide having nasal mucosal permeability. (c) A peptide having an amino acid sequence represented by the reverse sequence of (a) or (b), the peptide having nasal mucosal permeability.

摘要翻译： 通过包含亲水生物活性物质和下列（a）至（c）中任一项的鼻腔给药用药物组合物，条件是排除C末端酰胺化肽，具有低透性吸收能力的亲水性生物活性物质，其具有 通常只能通过注射给药可以鼻腔给药。 这种药物组合物可用于改善由注射给药引起的患者的疼痛和不便。 （a）具有SEQ ID NO：1所示的氨基酸序列的肽。 （b）具有鼻粘膜通透性的肽，除了缺失，取代和/或添加一个或数个氨基酸以外，具有SEQ ID NO：1所示相同氨基酸序列的肽。 （c）具有由（a）或（b）的相反序列表示的氨基酸序列的肽，该肽具有鼻粘膜通透性。

公开(公告)号：US20060241922A1

公开(公告)日：2006-10-26

申请号：US11340553

申请日：2006-01-27

申请人： Chosei Kaseda ,  Kozo Takayama

发明人： Chosei Kaseda ,  Kozo Takayama

IPC分类号： G06F17/10

CPC分类号： G06F17/504 ,  G06Q10/04

摘要： The method first creates a BS database by randomly sampling experimental data items from an experimental data DB storing a plurality of experimental data items having n (n is an integer of 2 or larger) kinds of variates. It then identificates an n-dimensional sampling curve or surface model approximating a correlation of the n kinds of variates with reference to the BS database, and stores the model into a BS optimum solution database. The method then repeats the creation of the BS database and the identification of the sampling curve or surface model, thereby creating the optimum solution database. Finally, the method obtains a mean and variance of the optimum solution with reference to the BS optimum solution database and estimates the reliability of the optimum solution from these values.

摘要翻译： 该方法首先通过从存储多个具有n（n是2或更大的整数）种类的实验数据项的实验数据DB中随机抽取实验数据项来创建BS数据库。 然后，它将基于BS数据库的n维变量的相关性的n维采样曲线或表面模型识别，并将该模型存储到BS最优解数据库中。 然后，该方法重复BS数据库的创建和采样曲线或表面模型的识别，从而创建最佳解决方案数据库。 最后，该方法参照BS最优解数据库获得最优解的均值和方差，并从这些值估计最优解的可靠性。

公开(公告)号：US08772449B2

公开(公告)日：2014-07-08

申请号：US13321176

申请日：2010-05-19

申请人： Mariko Morishita ,  Kozo Takayama ,  Reiji Nishio ,  Nobuo Ida

发明人： Mariko Morishita ,  Kozo Takayama ,  Reiji Nishio ,  Nobuo Ida

IPC分类号： C07K7/08 ,  A61K38/10 ,  C07K14/435 ,  A61K9/00

CPC分类号： C07K7/08 ,  A61K9/0053 ,  A61K9/007 ,  A61K9/0073 ,  A61K38/10 ,  C07K14/43581

摘要： A cell-penetrating peptide of (A) to (D) below gives cell membrane permeability and transmucosal absorbability to a physiologically active substance: (A) a peptide having the amino acid sequence of SEQ ID NO:1; (B) a peptide represented by SEQ ID NO:1 except that one or several basic amino acids are changed; (C) a peptide represented by SEQ ID NO:1 except that 1 to 5 amino acids are changed; (D) a peptide having: the reverse sequence of any of (A) to (C); an amino acid sequence which is the same as the reverse sequence of (A) except that one or several basic amino acids are changed; or an amino acid sequence which is the same as the reverse sequence of (A) except that 1 to 5 amino acids are changed.

摘要翻译： （A）〜（D）的细胞穿透肽赋予生理活性物质的细胞膜通透性和经粘膜吸收性：（A）具有SEQ ID NO：1的氨基酸序列的肽; （B）除了一个或几个碱性氨基酸改变之外，由SEQ ID NO：1表示的肽; （C）除了1〜5个氨基酸改变之外，由SEQ ID NO：1表示的肽; （D）具有（A）至（C）中任一个的相反序列的肽; 与（A）的相反序列相同的氨基酸序列，除了一个或多个碱性氨基酸改变; 或与（A）的相反序列相同的氨基酸序列，只是改变1至5个氨基酸。

公开(公告)号：US07734564B2

公开(公告)日：2010-06-08

申请号：US11340553

申请日：2006-01-27

申请人： Chosei Kaseda ,  Kozo Takayama

发明人： Chosei Kaseda ,  Kozo Takayama

IPC分类号： G06F15/00 ,  G06F15/18

CPC分类号： G06F17/504 ,  G06Q10/04

摘要： The method first creates a BS database by randomly sampling experimental data items from an experimental data DB storing a plurality of experimental data items having n (n is an integer of 2 or larger) kinds of variates. It then identificates an n-dimensional sampling curve or surface model approximating a correlation of the n kinds of variates with reference to the BS database, and stores the model into a BS optimum solution database. The method then repeats the creation of the BS database and the identification of the sampling curve or surface model, thereby creating the optimum solution database. Finally, the method obtains a mean and variance of the optimum solution with reference to the BS optimum solution database and estimates the reliability of the optimum solution from these values.

摘要翻译： 该方法首先通过从存储多个具有n（n是2或更大的整数）种类的实验数据项的实验数据DB中随机抽取实验数据项来创建BS数据库。 然后，它将基于BS数据库的n维变量的相关性的n维采样曲线或表面模型识别，并将该模型存储到BS最优解数据库中。 然后，该方法重复BS数据库的创建和采样曲线或表面模型的识别，从而创建最佳解决方案数据库。 最后，该方法参照BS最优解数据库获得最优解的均值和方差，并从这些值估计最优解的可靠性。

公开(公告)号：US20130084257A1

公开(公告)日：2013-04-04

申请号：US13703827

申请日：2011-06-16

申请人： Kenya Ishida ,  Yasuko Obata ,  Kozo Takayama

发明人： Kenya Ishida ,  Yasuko Obata ,  Kozo Takayama

IPC分类号： A61K31/075 ,  A61K31/08 ,  A61K31/045

CPC分类号： A61K31/075 ,  A61K8/34 ,  A61K8/345 ,  A61K9/0014 ,  A61K9/06 ,  A61K9/7007 ,  A61K9/7023 ,  A61K9/7084 ,  A61K31/045 ,  A61K31/08 ,  A61K47/10 ,  A61Q19/00

摘要： The present invention provides a substance which promotes the transdermal absorption of a pharmacologically active component while little irritating the skin. The present invention relates to a transdermal absorption promoter which comprises, as the active component, at least one member selected from among isopulegol, 2-(menthoxy)ethanol and 2-methyl-3-(menthoxy)propane-1,2-diol; and an external skin formulation which comprises a pharmacologically active component such as a psychotropic component, an anti-inflammatory component, an analgesic component, an antipyretic component, a whitening component or a hair growth-promoting component, together with the aforesaid transdermal absorption promoter.

摘要翻译： 本发明提供促进药物活性成分的透皮吸收，同时刺激皮肤的物质。 本发明涉及一种透皮吸收促进剂，其包含选自异胡醇，2-（薄荷氧基）乙醇和2-甲基-3-（薄荷氧基）丙烷-1,2-二醇中的至少一种作为活性成分的透皮吸收促进剂; 以及外用皮肤制剂，其与上述透皮吸收促进剂一起包含药理活性成分如精神药物成分，抗炎成分，止痛成分，解热成分，美白成分或毛发生长促进成分。

公开(公告)号：US20080182907A1

公开(公告)日：2008-07-31

申请号：US12010718

申请日：2008-01-29

申请人： Kozo Takayama ,  Yasuko Obata ,  Satoshi Nomoto

发明人： Kozo Takayama ,  Yasuko Obata ,  Satoshi Nomoto

IPC分类号： A61K31/135 ,  A61P29/00

CPC分类号： A61K31/135

摘要： An analgesic composition for external application for increasing the percutaneous permeability of tramadol or a pharmaceutically acceptable salt thereof and for achieving a quick pharmacological effect. The analgesic composition includes tramadol or a pharmaceutically acceptable salt thereof, a menthol substance and a pyrrolidone compound.

摘要翻译： 一种用于增加曲马多或其药学上可接受的盐的经皮通透性并用于实现快速药理作用的外用施用镇痛组合物。 镇痛组合物包括曲马多或其药学上可接受的盐，薄荷醇物质和吡咯烷酮化合物。