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1. 发明授权

US06936591B2 Amorphous 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A, process for preparing the same, and uses thereof 失效
标题翻译：无定形9-脱氧-9a-氮杂-9a-甲基-9a-高红霉素A，其制备方法及其用途
公开(公告)号：US06936591B2
公开(公告)日：2005-08-30
申请号：US10624911
申请日：2003-07-21
申请人： Miljenko Dumić , Mladen Vinković , Marina Oresic , Ernest Mestrovic , Aleksandar Danilovski , Alojz Dumbovic , Knezevic Zdravka , Gorjana Lazarevski , Darko Filic , Dominik Cincic , Katica Lazaric , Dejan-Kresimir Bucar
发明人： Miljenko Dumić , Mladen Vinković , Marina Oresic , Ernest Mestrovic , Aleksandar Danilovski , Alojz Dumbovic , Knezevic Zdravka , Gorjana Lazarevski , Darko Filic , Dominik Cincic , Katica Lazaric , Dejan-Kresimir Bucar
IPC分类号： C07H17/08 , A61K31/70 , C07H1/00
CPC分类号： C07H17/08
摘要： Substantially pure amorphous 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A. In addition, this disclosure is directed to a process for the preparation thereof from crude 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A via orthorhombic isostructural pseudopolymorphs of 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A, of the general formula I: wherein S represents a water-miscible or water-immiscible organic solvent, characterized by the orthorhombic space group P212121, with average unit cell parameters a=8.2 to 9.7 Å, b=11.5 to 13.5 Å, c=44.5 to 47.0 Å, α=β=γ=90°, wherein a, b and c represent the crystal axes lengths and α, β and γ represent the angles between the crystal axes. In addition, pharmaceutical compositions containing the substantially pure amorphous 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A are disclosed, as well as a method for the treatment of bacterial and protozoal infections, and inflammation related diseases in humans and animals by administration of a pharmaceutical composition containing same.
摘要翻译：基本上纯的无定形9-脱氧-9a-氮杂-9a-甲基-9a-高红霉素A.此外，本发明涉及一种由9-脱氧-9a-氮杂-9a-甲基-9a- 通过通式I的9-脱氧-9a-氮杂-9a-甲基-9a-高红霉素A的正交同构异构体假多晶型物的同型红霉素A：其中S表示水混溶性或水不混溶性有机溶剂，其特征在于正交空间群其中平均单元电池参数a = 8.2至9.7，b = 11.5至13.5，c = 44.5 至47.0A，α=β=γ= 90°，其中a，b和c表示晶轴长度，α，β和γ表示晶轴之间的角度。此外，公开了含有基本上纯的无定形9-脱氧-9a-氮杂-9a-甲基-9a-高红霉素A的药物组合物，以及用于治疗细菌和原生动物感染以及与人类发生炎症有关的疾病的方法动物通过施用含有它们的药物组合物。

2. 发明申请

US20040097434A1 Novel nonsteroidal anti-inflammatory substances, compositions and methods for their use 失效
标题翻译：新型非甾体抗炎物质，其使用的组合物和方法
公开(公告)号：US20040097434A1
公开(公告)日：2004-05-20
申请号：US10615010
申请日：2003-07-07
申请人： PLIVA Pharmaceutical Industry, Incorporated
发明人： Mladen Mercep , Milan Mesic , Linda Tomaskovic , Stribor Markovic
IPC分类号： A61K031/7048 , C07H017/08
CPC分类号： C07H17/00
摘要： The present invention relates (a) to new compounds represented by Formula I: 1 wherein M represents a macrolide subunit (macrolide moiety) derived from macrolide possessing the property of accumulation in inflammatory cells, D represents a nonsteroidal subunit (nonsteroidal moiety) derived from nonsteroid drug with anti-inflammatory, analgesic and/or antipyretic activity (NSAID) and L represents a linking group covalently linking M and D; (b) to their pharmacologically acceptable salts, prodrugs and solvates, (c) to processes and intermediates for their preparation, and (d) to their use in the treatment of inflammatory diseases and conditions in humans and animals.
摘要翻译：本发明涉及（a）由式I表示的新化合物：其中M表示衍生自具有在炎性细胞中积累性质的大环内酯的大环内酯亚单位（大环内酯部分），D表示衍生自非类固醇药物的非甾体亚基（非甾体化合物）具有抗炎，镇痛和/或解热活性（NSAID），L代表共价连接M和D的连接基团; （b）其药理学上可接受的盐，前药和溶剂化物，（c）其制备方法和中间体，和（d）其用于治疗人和动物的炎性疾病和病症。

3. 发明申请

US20040014685A1 Compounds, compositions and methods for treatment of inflammatory diseases and conditions 失效
标题翻译：用于治疗炎性疾病和病症的化合物，组合物和方法
公开(公告)号：US20040014685A1
公开(公告)日：2004-01-22
申请号：US10615716
申请日：2003-07-08
申请人： PLIVA Pharmaceutical Industry, Incorporated
发明人： Mladen Mercep , Milan Mesic , Linda Tomaskovic , Stribor Markovic , Oresta Makaruha , Visnja Poljak
IPC分类号： A61K031/7048 , A61K031/585 , C07J017/00
CPC分类号： C07H17/00
摘要： The present invention relates (a) to new compounds represented by Formula I: 1 wherein M represents a macrolide subunit (macrolide moiety) derived from macrolide possessing the property of accumulation in inflammatory cells, S represents a steroid subunit (steroid moiety) derived from steroid drug with anti-inflammatory activity and L represents a linker molecule linking M and S, (b) to their pharmacologically acceptable salts, prodrugs and solvates, (c) to processes and intermediates for their preparation, and (d) to their use in the treatment of inflammatory diseases and conditions in humans and animals. Such compounds inhibit many cytokines and immune mediators involved in immune responses which cause inflammation, allergy, or alloimmunity, including without limitation IL-1, 2, 4, 5, 6, 10, 12, GMCSF, ICAM, and TNF-null Importantly, anti-inflammatory steroids exert a direct anti-inflammatory effect through binding to the glucocorticosteroid receptor.
摘要翻译：本发明涉及（a）由式I表示的新化合物：其中M表示衍生自具有在炎性细胞中积累性质的大环内酯的大环内酯亚单位（大环内酯部分），S代表衍生自类固醇药物的类固醇亚单位（类固醇部分）具有抗炎活性，L表示连接M和S的连接分子，（b）其药理学上可接受的盐，前药和溶剂合物，（c）其制备方法和中间体，以及（d）其在治疗中的用途的炎症疾病和病症在人类和动物。这些化合物抑制许多细胞因子和参与引起炎症，变态反应或同种异体免疫的免疫应答的免疫介质，包括但不限于IL-1,2,4,5,6,10,12，GMCSF，ICAM和TNF-α。重要的是，抗炎类固醇通过结合糖皮质激素受体发挥直接的抗炎作用。

4. 发明申请

US20040092460A1 Novel amorphous 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A, process for preparing the same, and uses thereof 失效
标题翻译：新型无定形9-脱氧-9a-氮杂-9a-甲基-9a-高红霉素A，其制备方法及其用途
公开(公告)号：US20040092460A1
公开(公告)日：2004-05-13
申请号：US10624911
申请日：2003-07-21
申请人： Pliva Pharmaceutical Industry, Incorporated
发明人： Miljenko Dumic , Mladen Vinkovic , Marina Oresic , Ernest Mestrovic , Aleksandar Danilovski , Alojz Dumbovic , Knezevic Zdravka , Gorjana Lazarevski , Darko Filic , Dominik Cincic , Katica Lazaric , Dejan-Kresimir Bucar
IPC分类号： C07H017/08 , A61K031/7052
CPC分类号： C07H17/08
摘要： Substantially pure amorphous 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A. In addition, this disclosure is directed to a process for the preparation thereof from crude 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A via orthorhombic isostructural pseudopolymorphs of 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A, of the general formula I 1 wherein S represents a water-miscible or water-immiscible organic solvent, characterized by the orthorhombic space group P212121, with average unit cell parameters anull8.2 to 9.7 null, bnull11.5 to 13.5 null, cnull44.5 to 47.0 null, nullnullnullnullnullnull90null, wherein a, b and c represent the crystal axes lengths and null, null and null represent the angles between the crystal axes. In addition, pharmaceutical compositions containing the substantially pure amorphous 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A are disclosed, as well as a method for the treatment of bacterial and protozoal infections, and inflammation related diseases in humans and animals by administration of a pharmaceutical composition containing same.
摘要翻译：基本上纯的无定形9-脱氧-9a-氮杂-9a-甲基-9a-高红霉素A.此外，本发明涉及一种由9-脱氧-9a-氮杂-9a-甲基-9a- 通过通式I的9-脱氧-9a-氮杂-9a-甲基-9a-高红霉素A的斜方晶异构体假结构的异红霉素A，其中S表示与水可混溶或水不混溶的有机溶剂，其特征在于斜方形空间群P212121 ，平均晶胞参数a = 8.2至9.7，b = 11.5至13.5，c = 44.5至47.0，α=β=γ= 90°，其中a，b和c表示晶轴长度和α， β和γ表示晶轴之间的角度。此外，公开了含有基本上纯的无定形9-脱氧-9a-氮杂-9a-甲基-9a-高红霉素A的药物组合物，以及用于治疗细菌和原生动物感染以及与人类发生炎症有关的疾病的方法动物通过施用含有它们的药物组合物。

5. 发明公开

EP0743854A1 ANTI-TUMOUR MEDICAL PREPARATION ON THE BASIS OF CARBOPLATIN AND THE METHOD OF ITS PRODUCTION 失效转让
标题翻译：抗癌药物引起，第三方卡博白金和方法
公开(公告)号：EP0743854A1
公开(公告)日：1996-11-27
申请号：EP94904944.0
申请日：1994-02-07
申请人： Kiss Laboratories S.R.O.
发明人： KISS, Frantisek , KISSOVA, Ludmila
IPC分类号： A61K9 , A61K31 , A61K47
CPC分类号： A61K9/0019 , A61K31/555 , A61K47/12
摘要： Anti-tumour medical preparation based on the carboplatin cytostatic compound whose long-term stability and biologic activity in aqueous solution at the pH value from 2.0 to 7.0 is reached by the presence of the 1,1-cyclobutanedicarboxylic acid and/or sodium and/or potassium and/or its ammonium salts and/or some pharmaceutically acceptable auxiliary compounds and suitable method of production.

6. 发明授权

EP0743854B1 ANTI-TUMOUR MEDICAL PREPARATION ON THE BASIS OF CARBOPLATIN AND THE METHOD OF ITS PRODUCTION 失效转让
标题翻译：抗肿瘤药基于卡博铂及其制造
公开(公告)号：EP0743854B1
公开(公告)日：2001-06-27
申请号：EP94904944.9
申请日：1994-02-07
申请人： PLIVA, pharmaceutical industry incorporated
发明人： KISS, Frantisek , KISSOVA, Ludmila
IPC分类号： A61K31/28 , A61K47/12
CPC分类号： A61K9/0019 , A61K31/555 , A61K47/12
摘要： Anti-tumour medical preparation based on the carboplatin cytostatic compound whose long-term stability and biologic activity in aqueous solution at the pH value from 2.0 to 7.0 is reached by the presence of the 1,1-cyclobutanedicarboxylic acid and/or sodium and/or potassium and/or its ammonium salts and/or some pharmaceutically acceptable auxiliary compounds and suitable method of production.

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