公开(公告)号：US06673812B1

公开(公告)日：2004-01-06

申请号：US09529354

申请日：2000-04-13

申请人： Mitsuyoshi Azuma ,  Yukuo Yoshida ,  Mitsunori Waki ,  Masayoshi Uehata

发明人： Mitsuyoshi Azuma ,  Yukuo Yoshida ,  Mitsunori Waki ,  Masayoshi Uehata

IPC分类号： A61K3144

CPC分类号： A61K31/551 ,  A61K31/00 ,  A61K31/437 ,  A61K31/4409 ,  A61K31/4545 ,  A61K31/496 ,  Y10S514/912 ,  Y10S514/913

摘要： An agent for the prophylaxis and treatment of glaucoma, which contains a compound having a Rho kinase inhibitory activity, particularly an agent for the prophylaxis and treatment of glaucoma, which contains a compound of the formula (I) wherein each symbol is as defined in the specification, as the compound having a Rho kinase inhibitory activity, is provided. The agent for the prophylaxis and treatment of glaucoma of the present invention is a novel agent for the prophylaxis and treatment of glaucoma and has intraocular pressure lowering action, optic disc blood flow improving action and aqueous humor outflow promoting action.

摘要翻译： 一种用于预防和治疗青光眼的药剂，其含有具有Rho激酶抑制活性的化合物，特别是用于预防和治疗青光眼的药物，其含有式（I）化合物，其中每个符号如 规定，作为具有Rho激酶抑制活性的化合物。 用于预防和治疗本发明青光眼的药剂是用于预防和治疗青光眼的新型药剂，具有降眼压作用，视盘血流改善作用和房水流出促进作用。

公开(公告)号：US06649625B2

公开(公告)日：2003-11-18

申请号：US10298674

申请日：2002-11-19

申请人： Mitsuyoshi Azuma ,  Yukuo Yoshida ,  Mitsunori Waki ,  Masayoshi Uehata

发明人： Mitsuyoshi Azuma ,  Yukuo Yoshida ,  Mitsunori Waki ,  Masayoshi Uehata

IPC分类号： A61K3144

CPC分类号： A61K31/551 ,  A61K31/00 ,  A61K31/437 ,  A61K31/4409 ,  A61K31/4545 ,  A61K31/496 ,  Y10S514/912 ,  Y10S514/913

摘要： An agent for the prophylaxis and treatment of glaucoma, which contains a compound having a Rho kinase inhibitory activity, particularly an agent for the prophylaxis and treatment of glaucoma, which contains a compound of the formula (I) wherein each symbol is as defined in the specification, as the compound having a Rho kinase inhibitory activity, is provided. The agent for the prophylaxis and treatment of glaucoma of the present invention is a novel agent for the prophylaxis and treatment of glaucoma and has intraocular pressure lowering action, optic disc blood flow improving action and aqueous humor outflow promoting action.

摘要翻译： 一种用于预防和治疗青光眼的药剂，其含有具有Rho激酶抑制活性的化合物，特别是用于预防和治疗青光眼的药物，其含有式（I）的化合物，其中每个符号如 规定，作为具有Rho激酶抑制活性的化合物。 用于预防和治疗本发明青光眼的药剂是用于预防和治疗青光眼的新型药剂，具有降眼压作用，视盘血流改善作用和房水流出促进作用。

公开(公告)号：US06423691B1

公开(公告)日：2002-07-23

申请号：US09623393

申请日：2000-09-05

申请人： Mitsuyoshi Azuma ,  Yukuo Yoshida ,  Yuji Sakamoto ,  Jun Inoue

发明人： Mitsuyoshi Azuma ,  Yukuo Yoshida ,  Yuji Sakamoto ,  Jun Inoue

IPC分类号： A61K3800

CPC分类号： A61K38/00 ,  A61K31/18

摘要： A pharmaceutical composition for the prophylaxis and therapy of a disease arising from ocular fundus tissue cytopathy such as retinochoroidal disease, glaucoma, and posterior complication arising form photocoagulation, which contains, as an active ingredient, a compound of formula (I) wherein R1 represents an alkyl group having 1 to 4 carbon atoms or an aryl group having 6 to 10 carbon atoms which is optionally substituted; R2 and R3 may be the same or different and each represents hydrogen or an alkyl group having 1 to 4 carbon atoms or R2 and R3 may jointly form a ring having 3 to 7 carbon atoms; and R4 represents a lower alkyl group which substituted by aryl, cycloalkyl, or aromatic heterocyclic residue, or a pharmaceutically acceptable salt thereof.

摘要翻译： 一种用于预防和治疗由眼底组织细胞病变（例如视网膜色素性疾病，青光眼和由光凝产生的后期并发症）引起的疾病的药物组合物，其包含作为活性成分的式（I）化合物，其中R 1表示 具有1至4个碳原子的烷基或任选被取代的具有6至10个碳原子的芳基; R2和R3可以相同或不同，各自表示氢或具有1-4个碳原子的烷基，或者R2和R3可以共同形成具有3至7个碳原子的环; R 4表示被芳基，环烷基或芳香杂环残基取代的低级烷基或其药学上可接受的盐。

公开(公告)号：US06342531B1

公开(公告)日：2002-01-29

申请号：US09646529

申请日：2000-09-19

申请人： Mitsuyoshi Azuma ,  Yukuo Yoshida ,  Yuji Sakamoto ,  Jun Inoue

发明人： Mitsuyoshi Azuma ,  Yukuo Yoshida ,  Yuji Sakamoto ,  Jun Inoue

IPC分类号： A61K3118

CPC分类号： A61K31/18 ,  A61K31/16 ,  A61K38/05

摘要： A pharmaceutical composition for the prophylaxis and therapy of brain tissue impairment, which contains, as an active ingredient, a compound of the following formula (I) wherein R1 represents an alkyl group having 1-4 carbon atoms or an aryl group having 6-10 carbon atoms which is optionally substituted; R2 and R3 may be the same or different and each represents hydrogen or an alkyl group having 1-4 carbon atoms or R2 and R3 may jointly form a ring having 3-7 carbon atoms; and R4 represents a lower alkyl group which is optionally substituted by aryl, cycloalkyl, or aromatic heterocyclic residue, or a pharmaceutically acceptable salt thereof.

摘要翻译： 一种用于预防和治疗脑组织损伤的药物组合物，其包含作为活性成分的下式（I）的化合物，其中R 1表示具有1-4个碳原子的烷基或具有6-10的芳基 任选取代的碳原子; R2和R3可以相同或不同，各自表示氢或具有1-4个碳原子的烷基，或者R2和R3可以共同形成具有3-7个碳原子的环; R 4表示任选被芳基，环烷基或芳族杂环残基取代的低级烷基或其药学上可接受的盐。

公开(公告)号：US06214800B1

公开(公告)日：2001-04-10

申请号：US09282501

申请日：1999-04-09

申请人： Chiho Fukiage ,  Mitsuyoshi Azuma ,  Jun Inoue ,  Masayuki Nakamura ,  Yuka Yoshida

发明人： Chiho Fukiage ,  Mitsuyoshi Azuma ,  Jun Inoue ,  Masayuki Nakamura ,  Yuka Yoshida

IPC分类号： A61K3800

CPC分类号： A61K38/55 ,  C07C311/19 ,  C07D303/48

摘要： An angiogenesis inhibitor comprising a cysteine protease inhibitory compound. As the preferable cysteine protease inhibitory compound, epoxysuccinic acid compounds, peptide halohydrazide compounds, calpain inhibitory compounds, compounds of the formula (I) and compounds of the formula (VI) can be used. The angiogenesis inhibitor of the present invention suppresses new formation of blood vessels in the living tissues, so that it can be used as a superior therapeutic or prophylactic agent of angiogenesis associated with wound healing, inflammation, growth of tumor and the like; and angiogenesis as seen in diabetic retinopathy, prematurity retinopathy, retinal venous occlusion, senile discoid macular degeneration and the like, as well as for prevention of metastasis of tumors.

摘要翻译： 一种包含半胱氨酸蛋白酶抑制化合物的血管生成抑制剂。 作为优选的半胱氨酸蛋白酶抑制化合物，可以使用环氧琥珀酸化合物，肽卤代酰肼化合物，钙蛋白酶抑制化合物，式（I）的化合物和式（VI）的化合物。 本发明的血管发生抑制剂抑制活组织中血管的新形成，可以用作与伤口愈合，炎症，肿瘤生长等有关的血管生成的优异治疗或预防剂。 和血管生成，如糖尿病视网膜病变，早产儿视网膜病变，视网膜静脉闭塞，老年性盘状黄斑变性等，以及用于预防肿瘤转移。

公开(公告)号：US20110212899A1

公开(公告)日：2011-09-01

申请号：US11578796

申请日：2005-04-21

申请人： Yoshiko Takayama ,  Yoshikuni Nakamura ,  Yutaka Inoue ,  Chiho Yabuta ,  Mitsuyoshi Azuma ,  Satomi Onoue

发明人： Yoshiko Takayama ,  Yoshikuni Nakamura ,  Yutaka Inoue ,  Chiho Yabuta ,  Mitsuyoshi Azuma ,  Satomi Onoue

IPC分类号： A61K38/17 ,  A61P27/02

CPC分类号： A61K38/2278

摘要： It is intended to provide an agent for promoting corneal neuritogenesis containing PACAP, a PACAP derivative or a pharmaceutically acceptable salt thereof, in particular, an agent for promoting corneal neuritogenesis aiming at improving corneal sensitivity, treating dry eye and treating corneal epithelial injury due to an effect of promoting corneal neuritogenesis. This agent for promoting corneal neuritogenesis is useful as a drug for ameliorating reduction in corneal sensitivity following corneal surgeries such as laser keratonomy (LASIK) and corneal grafting or cataract surgery, reduction in corneal sensitivity accompanying corneal neurodegeneration and dry eye symptom and corneal epithelial injury accompanying such reduction in corneal sensitivity. Moreover, it is useful as a drug for ameliorating dry eye symptom, reduction in corneal sensitivity and corneal epithelial injury in patients with dry eye, and a drug for ameliorating corneal epithelial injury and dry eye symptom and reduction in corneal sensitivity accompanying therewith.

摘要翻译： 旨在提供用于促进包含PACAP，PACAP衍生物或其药学上可接受的盐的角膜神经发生的药剂，特别是用于促进角膜神经突发生的药物，其目的在于改善角膜敏感性，治疗干眼症并治疗角膜上皮损伤 促进角膜神经发生的作用。 用于促进角膜神经发生的药物可用作改善角膜手术如角膜手术（LASIK）和角膜移植术或白内障手​​术后角膜敏感性降低的药物，伴随角膜神经变性和干眼症状以及角膜上皮损伤伴随的角膜敏感性降低 角膜敏感度降低。 此外，它可用作改善干眼症状，减少干眼症患者的角膜敏感性和角膜上皮损伤的药物，以及用于改善角膜上皮损伤和干眼症状以及与之伴随的角膜敏感性降低的药物。

公开(公告)号：US07956072B2

公开(公告)日：2011-06-07

申请号：US12289748

申请日：2008-11-03

申请人： Yoshiko Takayama ,  Yoshikuni Nakamura ,  Jun Inoue ,  Mitsuyoshi Azuma

发明人： Yoshiko Takayama ,  Yoshikuni Nakamura ,  Jun Inoue ,  Mitsuyoshi Azuma

IPC分类号： A61K31/445 ,  A61K31/44

CPC分类号： C07D471/04 ,  A61K31/165 ,  A61K31/437 ,  A61K31/445 ,  A61K31/4745 ,  A61K31/501

摘要： The amide compound of the formula (I) [each symbol is as defined in the description] has a promoting action on neuritogenesis of trigeminal nerve cells, and the compound is useful as a corneal neuritogenesis promoter, an agent for recovering corneal sensitivity by promotion of corneal neuritogenesis, and an agent for treating dry eye.

摘要翻译： 式（I）的酰胺化合物[各符号如说明书中所定义]对三叉神经细胞的神经发生具有促进作用，并且该化合物可用作角膜神经发生促进剂，通过促进角膜神经发生促进剂来恢复角膜敏感性 角膜神经发生，以及用于治疗干眼症的药剂。

公开(公告)号：US06551999B1

公开(公告)日：2003-04-22

申请号：US09243822

申请日：1999-02-03

申请人： Chiho Fukiage ,  Mitsuyoshi Azuma ,  Jun Inoue ,  Masayuki Nakamura ,  Yuka Yoshida

发明人： Chiho Fukiage ,  Mitsuyoshi Azuma ,  Jun Inoue ,  Masayuki Nakamura ,  Yuka Yoshida

IPC分类号： C07K506

CPC分类号： A61K38/55 ,  C07C311/19 ,  C07D303/48

摘要： An angiogenesis inhibitor comprising a cysteine protease inhibitory compound. As the preferable cysteine protease inhibitory compound, epoxysuccinic acid compounds, peptide halohydrazide compounds, calpain inhibitory compounds, compounds of the formula (I) and compounds of the formula (VI) can be used. The angiogenesis inhibitor of the present invention suppresses new formation of blood vessels in the living tissues, so that it can be used as a superior therapeutic or prophylactic agent of angiogenesis associated with wound healing, inflammation, growth of tumor and the like; and angiogenesis as seen in diabetic retinopathy, prematurity retinopathy, retinal venous occlusion, senile discoid macular degeneration and the like, as well as for prevention of metastasis of tumors.

摘要翻译： 一种包含半胱氨酸蛋白酶抑制化合物的血管生成抑制剂。 作为优选的半胱氨酸蛋白酶抑制化合物，可以使用环氧琥珀酸化合物，肽卤代酰肼化合物，钙蛋白酶抑制化合物，式（I）的化合物和式（VI）的化合物。 本发明的血管发生抑制剂抑制活组织中血管的新形成，可以用作与伤口愈合，炎症，肿瘤生长等有关的血管生成的优异治疗或预防剂。 和血管生成，如糖尿病视网膜病变，早产儿视网膜病变，视网膜静脉闭塞，老年性盘状黄斑变性等，以及用于预防肿瘤转移。

公开(公告)号：US08268794B2

公开(公告)日：2012-09-18

申请号：US12672473

申请日：2008-08-05

申请人： Takeshi Nakajima ,  Emi Nakajima ,  Mitsuyoshi Azuma

发明人： Takeshi Nakajima ,  Emi Nakajima ,  Mitsuyoshi Azuma

IPC分类号： A61K48/00 ,  C07H21/02 ,  C07H21/04

CPC分类号： A61K45/06 ,  A61K31/7088 ,  A61K31/7105 ,  A61K31/713 ,  C12N15/113 ,  C12N15/1136 ,  C12N2310/11 ,  C12N2310/14

摘要： Provided is a pharmaceutical product exhibiting a high therapeutic effect in the treatment of retinal diseases associated with angiogenesis such as age-related macular degeneration, diabetic retinopathy and the like. A therapeutic agent for a retinal disease, containing a substance specifically inhibiting HIF-1α expression and a substance specifically inhibiting HIF-2α expression. The aforementioned inhibitory substances, which are active ingredients in the therapeutic agent of the present invention, are nucleic acids capable of inducing RNAi, antisense nucleic acids or ribozymes for HIF-1α and HIF-2α, or expression vectors thereof.

摘要翻译： 本发明提供在治疗与血管生成相关的视网膜疾病如老年性黄斑变性，糖尿病性视网膜病变等中具有高治疗效果的药物。 含有特异性抑制HIF-1α表达的物质的视网膜疾病治疗剂和特异性抑制HIF-2α表达的物质。 作为本发明的治疗剂中的活性成分的上述抑制物质是能够诱导HIF-1α和HIF-2α的RNAi，反义核酸或核酶的核酸或其表达载体。

公开(公告)号：US20110008891A1

公开(公告)日：2011-01-13

申请号：US12922084

申请日：2009-03-19

申请人： Takeshi Nakajima ,  Mitsuyoshi Azuma

发明人： Takeshi Nakajima ,  Mitsuyoshi Azuma

IPC分类号： C12N5/071 ,  C07K14/47

CPC分类号： C07K14/475 ,  A61K9/0048 ,  A61K38/00

摘要： The invention provides a polypeptide comprising the amino acid sequence of SEQ ID NO: 1, which is a particular partial sequence of lacritin, and having an amino acid length of not more than 70 residues. The polypeptide of the invention can promote adhesion between a cell and an extracellular matrix, and can promote tear fluid secretion from lacrimal gland acinar cells.

摘要翻译： 本发明提供了包含SEQ ID NO：1的氨基酸序列的多肽，其是lacritin的特定部分序列，并且具有不超过70个残基的氨基酸长度。 本发明的多肽可以促进细胞和细胞外基质之间的粘附，并且可以促进泪腺腺泡细胞的泪液分泌。