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1. 发明申请

WO2011003624A1 A PROCESS FOR THE PREPARATION AND PURIFICATION OF SOLIFENACIN SALTS 审中-公开
标题翻译：一种制备和纯化SOLIFENACIN SALTS的方法
公开(公告)号：WO2011003624A1
公开(公告)日：2011-01-13
申请号：PCT/EP2010/004204
申请日：2010-07-09
申请人： KRKA, d.d., Novo mesto , KLJAJIC, Alen , RUZIC, Milos , PRUDIC, Darja , PECAVAR, Anica , BUKOVEC, Polona , ZUPET, Rok
发明人： KLJAJIC, Alen , RUZIC, Milos , PRUDIC, Darja , PECAVAR, Anica , BUKOVEC, Polona , ZUPET, Rok
IPC分类号： C07D453/02
CPC分类号： C07D453/02
摘要： The invention relates to a preparation and purification processes of solifenacin salts, particularly to a crystallization process of solifenacin succinate, leading to high purity of the obtained product as well as to the desired average particle size and desired modality of the particle size distribution.
摘要翻译：本发明涉及solifenacin盐的制备和纯化方法，特别是涉及琥珀酸索非那新的结晶方法，导致所得产物的高纯度以及所需的平均粒度和所需的粒度分布模式。

2. 发明申请

WO2011006638A1 PROCESS FOR THE SYNTHESIS OF PALIPERIDONE 审中-公开
标题翻译：合成PALIPERIDONE的方法
公开(公告)号：WO2011006638A1
公开(公告)日：2011-01-20
申请号：PCT/EP2010/004258
申请日：2010-07-13
申请人： KRKA, D.D., NOVO MESTO , RUZIC, Milos , PECAVAR, Anica , PRUDIC, Darja , PLAPER, Igor , KLOBCAR, Andrej
发明人： RUZIC, Milos , PECAVAR, Anica , PRUDIC, Darja , PLAPER, Igor , KLOBCAR, Andrej
IPC分类号： C07D471/04 , A61K31/42 , A61P25/18
CPC分类号： C07D471/04
摘要： The invention describes an improved process for the synthesis and purification of paliperidone.
摘要翻译：本发明描述了利培酮的合成和纯化的改进方法。

3. 发明申请

WO2005016931A2 CRYSTALLISATION OF SOLID FORMS OF CLOPIDOGREL ADDITION SALTS 审中-公开
标题翻译：氯粘蛋白添加剂固体形态的结晶
公开(公告)号：WO2005016931A2
公开(公告)日：2005-02-24
申请号：PCT/EP2004/008989
申请日：2004-08-11
申请人： KRKA, TORVARNA ZDRAVIL, D.D., NOVO MESTO , KOTA-JORDAN, Berta , SIMONIC, Igor , ZUPET, Rok , RUZIC, Milos , GRCMAN, Marija , PECAVAR, Anica
发明人： KOTA-JORDAN, Berta , SIMONIC, Igor , ZUPET, Rok , RUZIC, Milos , GRCMAN, Marija , PECAVAR, Anica
IPC分类号： C07D495/04
CPC分类号： C07D495/04
摘要： The invention relates to a process for the preparation of form 1 and form 2 of clopidogrel hydrogen sulfate, a process for the preparation of amorphous clopidogrel hydrogen sulfate, the 2-propylsulfate of clopidogrel, the perchlorate of clopidogrel and methods for the preparation of these compounds.
摘要翻译：本发明涉及制备氯吡格雷硫酸氢盐的形式1和形式2的方法，制备无定形氯吡格雷硫酸氢盐，氯吡格雷的2-丙基硫酸盐，氯吡格雷的高氯酸盐和制备这些化合物的方法。

4. 发明申请

WO2011061292A1 A PROCESS FOR A PREPARATION OF MARBOFLOXACIN AND INTERMEDIATE THEREOF 审中-公开
标题翻译：一种制备马可氟菌素及其中间体的方法
公开(公告)号：WO2011061292A1
公开(公告)日：2011-05-26
申请号：PCT/EP2010/067828
申请日：2010-11-19
申请人： KRKA, TOVARNA ZDRAVIL, D.D., NOVO MESTO , ZUPET, Rok , ISKRA, Jernej , RUZIC, Milos , PECAVAR, Anica , KOLENC, Ivanka , PUCELJ, Jože , PLAPER, Igor
发明人： ZUPET, Rok , ISKRA, Jernej , RUZIC, Milos , PECAVAR, Anica , KOLENC, Ivanka , PUCELJ, Jože , PLAPER, Igor
IPC分类号： C07D215/58
CPC分类号： C07D215/58
摘要： The present invention describes a novel process for the preparation of marbof loxacin and intermediate thereof comprising reaction of ammonium hydroxide of formula (III), NR 1 R 2 R 3 R 4 , wherein R 1 , R 2 , R 3 and R 4 are independently selected from the group of H, alkyl, alkylaryl, aryl and/or heteroaryl, with compound of formula (II), wherein R is selected from H, alkyl, arylalkyl, alkali metal cation,, NH 4 cation, NR 1 R 2 R 3 R 4 cation; X is halogen, such as chloro, bromo, fluoro, piperazinyl, which may be substituted or unsubstituted, and R' is selected from H, formyl or COOAlkyl.
摘要翻译：本发明描述了一种新的制备马可福酯和其中间体的方法，其包括式（III）的氢氧化铵，NR1R2R3R4的反应，其中R 1，R 2，R 3和R 4独立地选自H，烷基，烷基芳基，芳基和/或杂芳基与式（II）化合物反应，其中R选自H，烷基，芳基烷基，碱金属阳离子，NH 4阳离子，NR 1 R 2 R 3 R 4; X是卤素，例如氯，溴，氟，哌嗪基，其可以是取代或未取代的，R'选自H，甲酰基或COOA烷基。

5. 发明申请

WO2011045073A1 PROCESS FOR THE AUTOMATED CLASSIFICATION AND ANALYSIS OF RAW DATA AND ITS USE IN THE OPTIMIZATION OF PROCESSES 审中-公开
标题翻译：自动分类和分析原始数据的过程及其在优化过程中的使用
公开(公告)号：WO2011045073A1
公开(公告)日：2011-04-21
申请号：PCT/EP2010/006309
申请日：2010-10-15
申请人： KRKA, TOVARNA ZDRAVIL , RUZIC, Milos , PECAVAR, Anica
发明人： RUZIC, Milos , PECAVAR, Anica
IPC分类号： G06F17/00
CPC分类号： G06F19/707 , G01N30/8658 , G06F19/703
摘要： The present invention relates to a process for the automated classification and analysis of data, said process comprising the steps of i) selecting an analytical method for use in an analytical experiment; ii) determining working parameters and conditions for the selected method, which parameters and conditions have an effect on the results obtained by using the selected method; iii) assigning to a set of data, said set of data including a) the type of the selected method and b) a specific combination of working parameters and conditions used in the analytical experiment a unique analytical method code (Hash value); iv) applying the method characterized by said Hash value to at least one reference sample and at least one or more further samples obtained from a process for preparing said sample, in which process at least one parameter such as temperature, solvent, or ratio of reactants etc. is to be optimized; v) storing the Hash value and the name of the sample as metadata together with the analytical results obtained in step (iv) as an analytical report; vi) automatically extracting, e.g. by using an extraction template or another extraction process, the relevant metadata from the analytical reports and transferring them to an enterprise content management system (ECMS) or other database systems; vii) automatically organizing the results according to the Hash value in the ECMS or any other suitable database system, viii) correlating the sets of data characterized by different Hash values on the basis of the reference sample measured for each Hash value, thereby creating a correlation matrix/table; ix) using the correlation matrix/table for multivariate analysis of the one or more of the parameters of the process resulting in the samples recited in step (iv); x) optionally, visualizing the results as one or more graphic charts; xi) using the results of steps (ix) and, optionally, (x) to optimize said one or more parameters of the process as defined in step (iv); xii) optionally, verifying the process on the laboratory, pilot plant or industrial scale.
摘要翻译：本发明涉及数据的自动分类和分析的方法，所述方法包括以下步骤：i）选择用于分析实验的分析方法; ii）确定所选方法的工作参数和条件，哪些参数和条件对通过使用所选方法获得的结果有影响; iii）分配一组数据，所述数据集包括a）所选方法的类型和b）分析实验中使用的工作参数和条件的特定组合，唯一的分析方法代码（哈希值）; iv）将由所述哈希值表征的方法应用于至少一个参考样品和从制备所述样品的方法获得的至少一个或多个另外的样品，其中至少一个参数例如温度，溶剂或反应物比例等待优化; v）将作为元数据的哈希值和样本名称与步骤（iv）中获得的分析结果一起存储为分析报告; vi）自动提取，例如通过使用提取模板或其他提取过程，分析报告中的相关元数据并将其转移到企业内容管理系统（ECMS）或其他数据库系统; vii）根据ECMS或任何其他合适的数据库系统中的哈希值自动组织结果，viii）基于为每个哈希值测量的参考样本，以不同哈希值为特征的数据集进行关联，从而产生相关性基质/表; ix）使用所述相关矩阵/表对所述过程的一个或多个参数进行多变量分析，得到步骤（iv）中所述的样品; x）可选地，将结果可视化为一个或多个图形图; xi）使用步骤（ix）的结果和（x）来优化步骤（iv）中定义的过程的所述一个或多个参数; xii）任选地，验证实验室，试验工厂或工业规模的过程。

6. 发明申请

WO2008015005A2 POLYMORPHIC FORMS OF ZIPRASIDONE SULFATES 审中-公开
标题翻译：硫酸锌的多形态
公开(公告)号：WO2008015005A2
公开(公告)日：2008-02-07
申请号：PCT/EP2007/006862
申请日：2007-08-02
申请人： KRKA , ZADNIK, Jernej , HVALEC, Miran , MAKUC, Simon , JURSIC, Urska , ZAJC, Natalija , RUZIC, Milos , SMRKOLJ, Matej , PECAVAR, Anica , STERGAR, Matej
发明人： ZADNIK, Jernej , HVALEC, Miran , MAKUC, Simon , JURSIC, Urska , ZAJC, Natalija , RUZIC, Milos , SMRKOLJ, Matej , PECAVAR, Anica , STERGAR, Matej
CPC分类号： C07D275/04 , C07D417/12
摘要： The present invention relates to novel polymorphic forms of Ziprasidone sulfates, as well as to a process for their preparation and pharmaceutical formulations containing it. The present polymorphic forms of Ziprasidone sulfates are characterized by small average particle sizes and high solubility bestowing the compounds an improved bioavailability.
摘要翻译：本发明涉及齐拉西酮硫酸盐的新型多晶型物，以及其制备方法和含有它的药物制剂。本发明的齐拉西酮硫酸盐的多晶型物的特征在于小平均粒度和高溶解度赋予化合物改进的生物利用度。

7. 发明申请

WO2009027533A1 PROCESS FOR PREPARING 2-SULFINYL-1H-BENZIMIDAZOLES 审中-公开
标题翻译：制备2-磺酰基-1H-苯并咪唑的方法
公开(公告)号：WO2009027533A1
公开(公告)日：2009-03-05
申请号：PCT/EP2008/061443
申请日：2008-08-29
申请人： KRKA, tovarna zdravil, d.d., Novo mesto , ISKRA, Jernei , STAVBER, Stojan , KOTAR JORDAN, Berta , RUZIC, Milos , SMODIS, Janez , ZUPET, Rok
发明人： ISKRA, Jernei , STAVBER, Stojan , KOTAR JORDAN, Berta , RUZIC, Milos , SMODIS, Janez , ZUPET, Rok
IPC分类号： C07D401/12
CPC分类号： C07D401/12
摘要： The present invention relates to a process for preparing 2-(2-pyridinylmethylsulfinyl)-1 H -benzimidazoles by oxidizing a thioether precursor in the presence of trifluoroethanol.
摘要翻译：本发明涉及通过在三氟乙醇存在下氧化硫醚前体制备2-（2-吡啶基甲基亚磺酰基）-1H-苯并咪唑的方法。

8. 发明申请

WO2023083926A1 SYNTHESIS OF (1R,2S,5S)-N-((S)-1-CYANO-2-((S)-2-OXOPYRROLIDIN-3-YL)ETHYL)-3-((S)-3,3-DIMETHYL-2- (2,2,2-TRIFLUOROACETAMIDO)BUTANOYL)-6,6-DIMETHYL-3-AZABICYCLO[3.1.0]HEXANE-2-CARBOXAMIDE 审中-公开
公开(公告)号：WO2023083926A1
公开(公告)日：2023-05-19
申请号：PCT/EP2022/081385
申请日：2022-11-10
申请人： KRKA, D.D., NOVO MESTO
发明人： ZUPANCIC, Silvo , RUZIC, Milos , SENICAR, Tanja , BEZENSEK, Jure
IPC分类号： C07D403/12
摘要： The invention relates to a process for the synthesis of (1R,2S,5S)-N-((S)-1-cyano-2-((S)-2-oxopyrroli- din-3-yl)ethyl)-3-((S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl)-6,6-dimethyl-3-azabicy- clo[3.1.0]hexane-2-carboxamide.

9. 发明公开

EP3067353A1 A PROCESS FOR THE PREPARATION OF SOLIFENACIN SALTS AND THEIR INCLUSION INTO PHARMACEUTICAL DOSAGE FORMS 有权
标题翻译：用于生产SOLIFENACINSALZEN和安装其药物剂型
公开(公告)号：EP3067353A1
公开(公告)日：2016-09-14
申请号：EP16156678.1
申请日：2009-07-29
申请人： KRKA, D.D., Novo Mesto
发明人： RUZIC, Milos , PRUDIC, Darja , PECAVAR, Anica , ZANOTTI-GEROSA, Antonio , STROPNIK, Tadej
IPC分类号： C07D453/02 , A61K31/439 , A61P13/10
CPC分类号： C07D453/02
摘要： The invention relates to the synthesis of solifenacin, the preparation of its salts and their inclusion into pharmaceutically acceptable dosage forms.
摘要翻译：本发明涉及一种索非那新的合成，它的盐和它们纳入药学上可接受的剂型的制备。

10. 发明授权

EP3067353B1 A PROCESS FOR THE PREPARATION OF SOLIFENACIN SALTS AND THEIR INCLUSION INTO PHARMACEUTICAL DOSAGE FORMS 有权
标题翻译：制备SOL烯酸盐及其包含在药物剂型中的方法
公开(公告)号：EP3067353B1
公开(公告)日：2017-11-22
申请号：EP16156678.1
申请日：2009-07-29
申请人： KRKA, D.D., Novo Mesto
发明人： RUZIC, Milos , PRUDIC, Darja , PECAVAR, Anica , ZANOTTI-GEROSA, Antonio , STROPNIK, Tadej
IPC分类号： C07D453/02 , A61K31/439 , A61P13/10
CPC分类号： C07D453/02
摘要： The invention relates to the synthesis of solifenacin, the preparation of its salts and their inclusion into pharmaceutically acceptable dosage forms.

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