公开(公告)号：US07767806B2

公开(公告)日：2010-08-03

申请号：US10571005

申请日：2004-09-08

申请人： Tai Hirakura ,  Teruo Nakamura ,  Tsuyoshi Shimoboji

发明人： Tai Hirakura ,  Teruo Nakamura ,  Tsuyoshi Shimoboji

IPC分类号： C07H5/04 ,  C07H1/00 ,  A61K31/728

CPC分类号： A61K9/5153 ,  A61K9/5161 ,  C08B37/0072 ,  C08G63/912

摘要： A hyaluronic acid modification product includes a polymer bonded to hyaluronic acid, the polymer being polylactic acid, polyglycolic acid or lactic acid-glycolic acid copolymer, providing a drug carrier which efficiently encapsulates low molecular weight drugs and provides sustained-release over a long term, control of blood residence, is well dispersible in an aqueous solution, and has excellent biocompatibility.

摘要翻译： 透明质酸改性产品包括与透明质酸结合的聚合物，聚合物是聚乳酸，聚乙醇酸或乳酸 - 乙醇酸共聚物，提供有效地包封低分子量药物并长期持续释放的药物载体， 血液停留的控制在水溶液中分散性良好，生物相容性优异。

公开(公告)号：US20090193826A1

公开(公告)日：2009-08-06

申请号：US11666247

申请日：2005-09-07

申请人： Kenji Yasugi ,  Teruo Nakamura ,  Tsuyoshi Shimoboji ,  Mika Sato

发明人： Kenji Yasugi ,  Teruo Nakamura ,  Tsuyoshi Shimoboji ,  Mika Sato

IPC分类号： F25B29/00 ,  F25D19/00 ,  F25D11/02

CPC分类号： F25D23/12 ,  F25D11/02 ,  F25D17/065 ,  F25D31/005 ,  F25D2317/061 ,  F25D2400/02 ,  F25D2400/16

摘要： There is provided a temperature switching compartment 3 which can switch the internal temperature thereof between a low temperature side at which a storage material is kept in cold storage and a high temperature side maintained at 50° C., to 80° C. at which cooked food is kept warm, by cooling with a cooler 17 and heating with a heater 15.

摘要翻译： 设置有一个温度切换室3，其可以将保存在冷藏中的储存材料的低温侧和保持在50℃的高温侧的低温侧切换到80℃的熟化温度 通过用冷却器17冷却并用加热器15加热来保持食物温暖。

公开(公告)号：US20090082266A1

公开(公告)日：2009-03-26

申请号：US11908278

申请日：2006-03-08

申请人： Teruo Nakamura ,  Tatsuya Kato ,  Hideyuki Togawa ,  Kenji Yasugi ,  Hiroko Konishi ,  Yasuo Sekimori ,  Tsuyoshi Shimoboji

发明人： Teruo Nakamura ,  Tatsuya Kato ,  Hideyuki Togawa ,  Kenji Yasugi ,  Hiroko Konishi ,  Yasuo Sekimori ,  Tsuyoshi Shimoboji

IPC分类号： A61K38/17 ,  A61P3/00

CPC分类号： C07K14/605 ,  A61K47/61 ,  C08B37/0072

摘要： To provide a GLP-1 analogue long-acting prophylactic or therapeutic agent for diabetes, diabetic complications and/or obesity due to diabetes which provides an extended half-life of a GLP-1 analogue in the blood to prevent frequent administration, and is biodegradable and safe.The present invention provides a conjugate obtained by binding, to a GLP-1 analogue into which a mercapto group is incorporated, water soluble hyaluronic acid modification product obtained by incorporating a substituent via an amide bond to the carboxyl group of glucuronic acid portion of hyaluronic acid as a derivative thereof, using a specific condensing agent in an aprotic polar solvent; and a prophylactic or therapeutic agent having a durable blood glucose lowering effect for diabetes, diabetic complications or obesity.

摘要翻译： 提供GLP-1类似物长效预防或治疗糖尿病，由于糖尿病导致的糖尿病并发症和/或肥胖症，其提供血液中GLP-1类似物的延长半衰期以防止频繁施用，并且是可生物降解的 安全。 本发明提供了通过与其中引入巯基的GLP-1类似物结合获得的缀合物，其通过将酰胺键引入到透明质酸的葡萄糖醛酸部分的羧基而获得的水溶性透明质酸改性产物 作为其衍生物，在非质子极性溶剂中使用特定的缩合剂; 以及对糖尿病，糖尿病并发症或肥胖具有持久的血糖降低作用的预防或治疗剂。

公开(公告)号：US20090148534A1

公开(公告)日：2009-06-11

申请号：US11662087

申请日：2005-09-07

申请人： Kenji Yasugi ,  Teruo Nakamura ,  Tsuyoshi Shimoboji ,  Mika Sato

发明人： Kenji Yasugi ,  Teruo Nakamura ,  Tsuyoshi Shimoboji ,  Mika Sato

IPC分类号： A61K9/14 ,  C07H1/00 ,  C07H3/00

CPC分类号： C08B37/0072 ,  A61K47/61 ,  C08J3/075 ,  C08J3/122 ,  C08L5/08

摘要： The present invention provides a water-soluble modified HA practically used as a drug carrier and a production method thereof. The present invention provides: a water-soluble modified hyaluronic acid, the residence time in blood of which is elongated to a practical level, which is produced by introducing a substituent into the carboxy group of the glucuronic acid of hyaluronic acid or a derivative thereof, via an amide bond, at a lower limit of an introduction rate of 5 mole % or more, using a BOP condensing agent in an aprotic polar solvent; and a production method thereof. Moreover, by cross-linking the modified hyaluronic acid, the present invention provides a hyaluronic acid gel capable of extremely long drug sustained-release even at the same cross-linking functional group introduction rate as that of the conventionally known gel.

摘要翻译： 本发明提供实际上用作药物载体的水溶性改性HA及其制备方法。 本发明提供：通过将透明质酸的葡糖醛酸或其衍生物的羧基引入取代基而产生的水溶性改性透明质酸，其在血液中的停留时间延长到实用水平， 通过酰胺键，在非极性极性溶剂中使用BOP缩合剂，在5摩尔％以上的引入速率的下限; 及其制造方法。 此外，通过交联改性透明质酸，本发明提供即使以与常规已知凝胶相同的交联官能团引入速率也能够极长的药物持续释放的透明质酸凝胶。

公开(公告)号：US20060110458A1

公开(公告)日：2006-05-25

申请号：US10536031

申请日：2003-11-21

申请人： Sei Hahn ,  Teruo Nakamura ,  Tsuyoshi Shimoboji

发明人： Sei Hahn ,  Teruo Nakamura ,  Tsuyoshi Shimoboji

IPC分类号： A61K31/728 ,  C08B37/00 ,  A61K9/14

CPC分类号： A61K9/06 ,  A61K9/0019 ,  A61K47/36 ,  C08B37/0072

摘要： The present invention aims to provide completely biodegradable and biocompatible sustained-release carriers for proteins or peptides, which allow encapsulation of the proteins or peptides at high encapsulation rates without inhibiting their biological activity. The present invention provides a method for preparing a sustained-release carrier, wherein in a solution in the presence of a protein or a peptide, a hyaluronic acid derivative having an unsaturated bond(s) or a mercapto group(s) introduced into hyaluronic acid is chemically crosslinked with a mercapto group-containing compound or an unsaturated bond-containing compound, respectively, to give a hydrogel. The method of the present invention enables efficient encapsulation of proteins or peptides while retaining their biological activity.

摘要翻译： 本发明旨在提供用于蛋白质或肽的完全可生物降解和生物相容的缓释载体，其允许以高包封率封装蛋白质或肽而不抑制其生物学活性。 本发明提供了一种制备缓释载体的方法，其中在蛋白质或肽存在下的溶液中，将具有引入透明质酸的不饱和键或巯基的透明质酸衍生物 分别与含巯基的化合物或含不饱和键的化合物进行化学交联，得到水凝胶。 本发明的方法能够有效地包封蛋白质或肽，同时保持其生物活性。

公开(公告)号：US20070031503A1

公开(公告)日：2007-02-08

申请号：US10571005

申请日：2004-09-08

申请人： Tai Hirakura ,  Teruo Nakamura

发明人： Tai Hirakura ,  Teruo Nakamura

IPC分类号： A61K9/50 ,  C08B37/00 ,  C08G63/91 ,  A61K9/16

CPC分类号： A61K9/5153 ,  A61K9/5161 ,  C08B37/0072 ,  C08G63/912

摘要： There is provided a drug carrier which has solved the problems of conventional drug carriers, which can encapsulate a low molecular drug efficiently, which can control a sustained release period for a long term, which can control blood residence, which has high dispersibility in an aqueous solution, and which is not problematical in safety. A drug carrier, which comprises injectable fine particles minimal in agglomeration between the particles, and which has excellent biocompatibility, is also provided. A hyaluronic acid modification product comprising hyaluronic acid or its derivative, and a polymer bonded together, the polymer being selected from polylactic acid, polyglycolic acid and lactic acid-glycolic acid copolymer, according to the present invention, provides a drug carrier which encapsulates a low molecular drug efficiently, which can control a sustained release period for a long term, which can control blood residence, which is well dispersible in an aqueous solution, and which is not problematical in safety. The hyaluronic acid modification product of the present invention also provides a drug carrier comprising injectable fine particles minimal in agglomeration between the particles, and having excellent biocompatibility.

摘要翻译： 提供了能够有效地包封低分子药物的常规药物载体的问题的药物载体，其可以长期控制持续释放时间，其可以控制血液存留，其在水性中具有高分散性 解决方案，这在安全性上没有问题。 还提供了一种药物载体，其包含颗粒之间附聚最少的可注射的微粒，并且其具有优异的生物相容性。 根据本发明的包含透明质酸或其衍生物的透明质酸改性产品和结合在一起的聚合物，聚合物选自聚乳酸，聚乙醇酸和乳酸 - 乙醇酸共聚物，提供了一种药物载体，其包封低 分子药物有效地控制长期的持续释放期，其可以控制在水溶液中良好分散的血液停留，并且这在安全性方面没有问题。 本发明的透明质酸改性产品还提供了一种药物载体，其包含颗粒之间最少聚集的可注射的微粒，并且具有优异的生物相容性。

公开(公告)号：US08143391B2

公开(公告)日：2012-03-27

申请号：US11662087

申请日：2005-09-07

申请人： Kenji Yasugi ,  Teruo Nakamura ,  Tsuyoshi Shimoboji ,  Mika Sato

发明人： Kenji Yasugi ,  Teruo Nakamura ,  Tsuyoshi Shimoboji ,  Mika Sato

IPC分类号： C07H1/00 ,  C08B37/08

CPC分类号： C08B37/0072 ,  A61K47/61 ,  C08J3/075 ,  C08J3/122 ,  C08L5/08

摘要： The present invention provides a water-soluble modified HA practically used as a drug carrier and a production method thereof. The present invention provides: a water-soluble modified hyaluronic acid, the residence time in blood of which is elongated to a practical level, which is produced by introducing a substituent into the carboxy group of the glucuronic acid of hyaluronic acid or a derivative thereof, via an amide bond, at a lower limit of an introduction ratio of 5 mole % or more, using a BOP condensing agent in an aprotic polar solvent; and a production method thereof. Moreover, by cross-linking the modified hyaluronic acid, the present invention provides a hyaluronic acid gel capable of extremely long drug sustained-release even at the same cross-linking functional group introduction ratio as that of the conventionally known gel.

摘要翻译： 本发明提供实际上用作药物载体的水溶性改性HA及其制备方法。 本发明提供：通过将透明质酸的葡糖醛酸或其衍生物的羧基引入取代基而产生的水溶性改性透明质酸，其在血液中的停留时间延长到实用水平， 通过酰胺键，在引发比为5摩尔％以上的下限，使用BOP缩合剂在非质子传递极性溶剂中; 及其制造方法。 此外，通过交联改性透明质酸，本发明提供即使以与常规已知凝胶相同的交联官能团引入比例，能够极长的药物持续释放的透明质酸凝胶。

公开(公告)号：US07816316B2

公开(公告)日：2010-10-19

申请号：US10536031

申请日：2003-11-21

申请人： Sei Kwang Hahn ,  Teruo Nakamura ,  Tsuyoshi Shimoboji

发明人： Sei Kwang Hahn ,  Teruo Nakamura ,  Tsuyoshi Shimoboji

IPC分类号： A61K38/02 ,  A61K31/728

CPC分类号： A61K9/06 ,  A61K9/0019 ,  A61K47/36 ,  C08B37/0072

摘要： The present invention aims to provide completely biodegradable and biocompatible sustained-release carriers for proteins or peptides, which allow encapsulation of the proteins or peptides at high encapsulation rates without inhibiting their biological activity. The present invention provides a method for preparing a sustained-release carrier, wherein in a solution in the presence of a protein or a peptide, a hyaluronic acid derivative having an unsaturated bond(s) or a mercapto group(s) introduced into hyaluronic acid is chemically crosslinked with a mercapto group-containing compound or an unsaturated bond-containing compound, respectively, to give a hydrogel. The method of the present invention enables efficient encapsulation of proteins or peptides while retaining their biological activity.

摘要翻译： 本发明旨在提供用于蛋白质或肽的完全可生物降解和生物相容的缓释载体，其允许以高包封率封装蛋白质或肽而不抑制其生物学活性。 本发明提供了一种制备缓释载体的方法，其中在蛋白质或肽存在下的溶液中，将具有引入透明质酸的不饱和键或巯基的透明质酸衍生物 分别与含巯基的化合物或含不饱和键的化合物进行化学交联，得到水凝胶。 本发明的方法能够有效地包封蛋白质或肽，同时保持其生物活性。

公开(公告)号：US08022191B2

公开(公告)日：2011-09-20

申请号：US11498053

申请日：2006-08-03

申请人： Teruo Nakamura ,  Yasuo Sekimori ,  Minoru Machida ,  Hiromitsu Kawata ,  Hajime Miyamoto

发明人： Teruo Nakamura ,  Yasuo Sekimori ,  Minoru Machida ,  Hiromitsu Kawata ,  Hajime Miyamoto

IPC分类号： A61K38/18

CPC分类号： C07K14/505 ,  A61K38/1816 ,  A61K47/60

摘要： The present invention provides a polyethylene glycol-conjugated erythropoietin (PEG-conjugated EPO) prepared by PEG conjugation on the lysine residue at position 52 of native erythropoietin (native EPO). In order to achieve more sustained efficacy without losing physiological activities of native EPO, a glycoprotein rich in sugar chains, there has been a need to develop a PEG-conjugated EPO with significantly sustained efficacy by introducing a controlled number of PEG molecules at controlled positions. This PEG-conjugated EPO addresses such a need and provides more sustained efficacy.

摘要翻译： 本发明提供通过PEG缀合在天然促红细胞生成素（天然EPO）的52位的赖氨酸残基上制备的聚乙二醇缀合的促红细胞生成素（PEG-缀合的EPO）。 为了获得更持久的功效而不损失富含糖链的糖蛋白的天然EPO的生理活性，需要通过在受控位置引入受控数量的PEG分子来开发具有显着持续功效的PEG-缀合的EPO。 这种PEG结合的EPO解决了这种需要并提供更持久的功效。

公开(公告)号：US06526040B1

公开(公告)日：2003-02-25

申请号：US09332966

申请日：1999-06-15

申请人： Teruo Nakamura

发明人： Teruo Nakamura

IPC分类号： H04J1500

CPC分类号： H04Q3/0016 ,  H04Q2213/1329 ,  H04Q2213/1338 ,  H04Q2213/13389

摘要： An interface connected to a local area network is mounted in each of data transfer circuits 19, 1a to 1c, 28, 29 and 36 for establishing logical connection of exchanges to one another such that it can connect a plurality of data transfer circuits provided in each exchange to one another. It is thus possible to obtain joint establishment of a logical mesh structure by individual data transfer circuits and, when a data transfer circuit receives data to be transferred to a different exchange from its own, obtain alleviation of the load in the own exchange with a process of data transfer between the data transfer circuits that is executed by using the local area network side interface.

摘要翻译： 连接到局域网的接口安装在每个数据传输电路19,1a至1c，28,29和36中，用于建立彼此之间的交换的逻辑连接，使得它可以连接多个数据传输电路 互相交流 因此，可以通过单独的数据传输电路来获得逻辑网格结构的联合建立，并且当数据传送电路从其自身接收到要传送到不同交换机的数据时，获得在自己交换中的负载的减轻与过程 在通过使用局域网侧接口执行的数据传送电路之间进行数据传送。