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1. 发明授权

US08334277B2 {4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl]phenoxy}phosphate or a pharmaceutically acceptable salt thereof, a production method therefor and a pharmaceutical composition for preventing and treating central nervous system disorders containing the same as an active component 有权
标题翻译： {4- [2-（二甲基氨基）-1-（1-羟基环己基）乙基]苯氧基}磷酸酯或其药学上可接受的盐，其制备方法和用于预防和治疗含有其的中枢神经系统疾病的药物组合物活性组分
公开(公告)号：US08334277B2
公开(公告)日：2012-12-18
申请号：US12990972
申请日：2009-05-08
申请人： Seok Won Kang , Jong Soo Chun , Heung Mo Kang , Eui Seok Hong , Kwang-Woo Chun , Young Seok Byun , Myung-Hwa Kim , Young Il Moon , Jei Man Ryu
发明人： Seok Won Kang , Jong Soo Chun , Heung Mo Kang , Eui Seok Hong , Kwang-Woo Chun , Young Seok Byun , Myung-Hwa Kim , Young Il Moon , Jei Man Ryu
IPC分类号： A61K31/045 , A61K31/137 , A61K31/661 , C07F9/12
CPC分类号： C07F9/12
摘要： The present invention relates to a novel {4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl]phenoxy}phosphate or a pharmaceutically acceptable salt thereof, a production method therefor and a pharmaceutical composition for preventing and treating central nervous system disorders which contains the same as an active component. The novel {4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl]phenoxy}phosphate or a pharmaceutically acceptable salt thereof according to the present invention can beneficially be used to prevent and treat central nervous system disorders since it exhibits an equivalent biological and pharmacological activity to venlafaxine and salts thereof which are known in the field, it has very little toxicity, and, in particular, it is outstandingly soluble in water as compared with prior-art venlafaxine derivatives.
摘要翻译：本发明涉及一种新型的{4- [2-（二甲基氨基）-1-（1-羟基环己基）乙基]苯氧基}磷酸酯或其药学上可接受的盐，其制备方法和用于预防和治疗中枢神经的药物组合物包含与活性成分相同的系统障碍。根据本发明的新型{4- [2-（二甲基氨基）-1-（1-羟基环己基）乙基]苯氧基}磷酸酯或其药学上可接受的盐可有利地用于预防和治疗中枢神经系统疾病，因为它表现出对本文已知的文拉法辛及其盐的等效生物和药理活性，其毒性非常小，特别是与现有技术的文拉法辛衍生物相比，其在水中的溶解性优异。

2. 发明申请

US20070179143A1 Tricyclic derivatives or pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them 审中-公开
标题翻译：三环衍生物或其药学上可接受的盐，它们的制剂和含有它们的药物组合物
公开(公告)号：US20070179143A1
公开(公告)日：2007-08-02
申请号：US10562615
申请日：2004-06-23
申请人： Myung-Hwa Kim , Kwnagwoo Chun , Jae-Won Chol , Bo-Young Joe , Sang-Woo Park , Kwang Kim , Byung-Kyu Oh , Jong-Hee Chol
发明人： Myung-Hwa Kim , Kwnagwoo Chun , Jae-Won Chol , Bo-Young Joe , Sang-Woo Park , Kwang Kim , Byung-Kyu Oh , Jong-Hee Chol
IPC分类号： A61K31/50 , A61K31/4965
CPC分类号： C07C323/41 , C07C381/00 , C07C2601/08 , C07C2603/34 , C07D213/81 , C07D213/82 , C07D307/68 , C07D333/38
摘要： The present invention relates to tricyclic derivatives or pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. More precisely, the present invention relates to tricyclic derivatives as colchicine derivatives, pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. Tricyclic derivatives of the present invention show very powerful cytotoxicity to cancer cell lines but were much less toxic than colchicine or taxol, confirmed through animal toxicity test. Tricyclic derivatives of the invention also decrease the volume and weight of a tumor and have a strong angiogenesis inhibiting activity in HUVEC cells. Thus, tricyclic derivatives of the present invention can effectively be used as an anticancer agent, anti-proliferation agent and an angiogenesis inhibitor.
摘要翻译：本发明涉及三环衍生物或其药学上可接受的盐，它们的制剂和含有它们的药物组合物。更准确地说，本发明涉及作为秋水仙素衍生物的三环衍生物，其药学上可接受的盐，其制备物和含有它们的药物组合物。本发明的三环衍生物对癌细胞系显示出非常强大的细胞毒性，但是通过动物毒性试验证实，它比秋水仙素或紫杉醇毒性低得多。本发明的三环衍生物还降低了肿瘤的体积和重量，并且在HUVEC细胞中具有强的血管生成抑制活性。因此，本发明的三环衍生物可以有效地用作抗癌剂，抗增生剂和血管发生抑制剂。

3. 发明申请

US20100317103A1 EFFICIENT GENERATION OF NEURAL PROGENITORS, NEURONS, AND DOPAMINERGIC NEURONS FROM HUMAN EMBRYONIC STEM CELLS 有权
标题翻译：人类胚胎干细胞的神经生长因子，神经元和多巴胺神经元的有效产生
公开(公告)号：US20100317103A1
公开(公告)日：2010-12-16
申请号：US12303670
申请日：2007-06-05
申请人： Myung Soo Cho , Myung-Hwa Kim , Young-Il Moon , Shin Yong Moon , Sun Kyung Oh , Hee Sun Kim , Dong-Wook Kim
发明人： Myung Soo Cho , Myung-Hwa Kim , Young-Il Moon , Shin Yong Moon , Sun Kyung Oh , Hee Sun Kim , Dong-Wook Kim
IPC分类号： C12N5/0735
CPC分类号： C12N5/0623 , C12N5/0619 , C12N2500/38 , C12N2500/44 , C12N2500/90 , C12N2501/115 , C12N2501/119 , C12N2501/41 , C12N2533/90
摘要： The present invention relates to a method for inducing the differentiation of neural progenitors, neurons, and dopaminergic neurons from human embryonic stem cells with high efficiency, in which neural selection can be performed by the selected media and physical methods. The invention has advantages such as higher efficiency, the effect of lowering cost and time, and maintenance of neural progenitors for a longer period of time, as compared to the known methods for inducing the differentiation into neural progenitors, neurons, and dopaminergic neurons. Accordingly, the method can stably generate cells used for treating Parkinson's disease or other nervous system diseases.
摘要翻译：本发明涉及一种以高效率从人类胚胎干细胞诱导神经祖细胞，神经元和多巴胺能神经元分化的方法，其中神经选择可以通过所选择的培养基和物理方法进行。与用于诱导分化成神经祖细胞，神经元和多巴胺能神经元的已知方法相比，本发明具有更高效率，降低成本和时间以及更长时间内神经祖细胞维持的优点。因此，该方法可以稳定地产生用于治疗帕金森病或其他神经系统疾病的细胞。

4. 发明授权

US08906395B2 Pharmaceutical composition in which solubility of partially soluble tricyclic derivative is improved 有权
标题翻译：其中部分可溶性三环衍生物的溶解度提高的药物组合物
公开(公告)号：US08906395B2
公开(公告)日：2014-12-09
申请号：US13806837
申请日：2011-06-23
申请人： Myung-Hwa Kim , Kwang-Woo Chun , In-Hae Ye , Jong-Hee Choi
发明人： Myung-Hwa Kim , Kwang-Woo Chun , In-Hae Ye , Jong-Hee Choi
IPC分类号： A61K47/28 , A61K9/127 , A61K9/51 , A61K9/00 , A61K31/01 , A61K31/66
CPC分类号： A61K47/28 , A61K9/0019 , A61K9/5123 , A61K31/01 , A61K31/66
摘要： A pharmaceutical composition includes lipid nanoparticles which include two or more of a phospholipid, cholesterol, and an ionic lipid, and a tricyclic derivative, wherein the solubility of the tricyclic derivative is improved. It is possible to solubilize a partially soluble tricyclic derivative in a high concentration even without using a solubilization aid harmful to the human body, to maintain improved solubility even if water is added for the use as an injection, and to show stability even if stored for a long time, by preparing lipid nanoparticles. Therefore, the lipid nanoparticles of the present invention can be used for preparing a pharmaceutical preparation containing a partially soluble tricyclic derivative as an active ingredient.
摘要翻译：药物组合物包括包含磷脂，胆固醇和离子脂质中的两种或更多种的脂质纳米颗粒和三环衍生物，其中三环衍生物的溶解度得到改善。即使不使用对人体有害的增溶助剂，也可以高浓度溶解部分可溶性三环衍生物，即使添加水作为注射剂也能保持改善的溶解性，并且即使存储很长时间，通过制备脂质纳米粒子。因此，本发明的脂质纳米颗粒可用于制备含有部分可溶性三环衍生物作为活性成分的药物制剂。

5. 发明授权

US08815891B2 Tricyclic derivative or pharmaceutically acceptable salts thereof, preparation method thereof, and pharmaceutical composition containing the same 有权
标题翻译：三环衍生物或其药学上可接受的盐，其制备方法和含有它们的药物组合物
公开(公告)号：US08815891B2
公开(公告)日：2014-08-26
申请号：US13128030
申请日：2009-11-11
申请人： Myung-Hwa Kim , Seung-Hyun Kim , Sae-Kwang Ku , Chun-Ho Park , Bo-Young Joe , Kwang-Woo Chun , In-Hae Ye , Jong-Hee Choi , Dong-Kyu Ryu , Ji-Seon Park , Han-Chang Lee , Ji-So Choi , Young-Chul Kim
发明人： Myung-Hwa Kim , Seung-Hyun Kim , Sae-Kwang Ku , Chun-Ho Park , Bo-Young Joe , Kwang-Woo Chun , In-Hae Ye , Jong-Hee Choi , Dong-Kyu Ryu , Ji-Seon Park , Han-Chang Lee , Ji-So Choi , Young-Chul Kim
IPC分类号： C07D471/06 , A61K31/4375
CPC分类号： C07D471/04
摘要： The present invention relates to a novel tricyclic derivative with efficient inhibitory activity against poly(ADP-ribose)polymerases (PARP) or pharmaceutically acceptable salts thereof, a preparation method thereof, and a pharmaceutical composition containing the same. The tricyclic derivative of the invention is useful for the prevention or treatment of diseases caused by excess PARP activity, especially neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic nephropathy, inflammatory diseases, osteoporosis, and cancer, by inhibiting the activity of poly(ADP-ribose)polymerases.
摘要翻译：本发明涉及对聚（ADP-核糖）聚合酶（PARP）或其药学上可接受的盐具有高效抑制活性的新型三环衍生物及其制备方法，以及含有它们的药物组合物。本发明的三环衍生物可用于预防或治疗由过量PARP活性引起的疾病，特别是神经性疼痛，神经变性疾病，心血管疾病，糖尿病性肾病，炎性疾病，骨质疏松症和癌症，通过抑制聚（ADP - 核糖）聚合酶。

6. 发明授权

US08742160B2 Method for preparing tricyclic derivatives 有权
标题翻译：三环衍生物的制备方法
公开(公告)号：US08742160B2
公开(公告)日：2014-06-03
申请号：US13381036
申请日：2010-06-29
申请人： Myung-Hwa Kim , In-Hae Ye , Jong-Hee Choi
发明人： Myung-Hwa Kim , In-Hae Ye , Jong-Hee Choi
IPC分类号： C07C321/28 , C07C323/42
CPC分类号： C07C319/20 , C07C51/06 , C07C65/01 , C07C67/08 , C07C67/30 , C07C233/65 , C07C235/42 , C07C2603/34 , C07D295/192 , C07C323/42 , C07C69/76
摘要： The present invention relates to a method for preparing a tricyclic derivative, and more particularly, to a method for preparing a tricyclic derivative intermediate with high yield and purity, the method including: introducing a hydroxy group by esterifying and substituting 2-fluoroisophthalic acid compound; introducing a piperidyl group; introducing a hydroxy group through reduction reaction; and then hydrolyzing the resultant compound, and to a method for preparing the tricyclic derivative using said intermediate. According to the method of the present invention, it is possible to provide a tricyclic derivative and an intermediate thereof with high productivity and economic feasibility as well as high purity and yield, by purifying a compound using re-crystallization unlike typical methods of using column chromatography. In addition, the method of the present invention can be usefully used for industrial mass production because sodium borohydride or lithium aluminum hydride with low risk of a fire is used unlike typical methods of using lithium borohydride which is not industrially applicable due to high risk of a fire.
摘要翻译：本发明涉及一种制备三环衍生物的方法，更具体地说涉及一种制备高产率和纯度的三环衍生物中间体的方法，其包括：通过酯化和取代2-氟间苯二甲酸化合物引入羟基; 引入哌啶基; 通过还原反应引入羟基; 然后水解所得化合物，以及使用所述中间体制备三环衍生物的方法。根据本发明的方法，通过使用重结晶纯化化合物，可以提供具有高生产率和经济可行性以及高纯度和收率的三环衍生物及其中间体，与使用柱色谱法的典型方法不同。此外，本发明的方法可以有用地用于工业大规模生产，因为使用低风险的硼氢化钠或氢化铝锂不同于使用不具有工业上适用的硼氢化锂的典型方法，这是因为高风险的火。

7. 发明授权

US08492149B2 Efficient generation of neural progenitors, neurons, and dopaminergic neurons from human embryonic stem cells 有权
标题翻译：从人胚胎干细胞中有效地产生神经祖细胞，神经元和多巴胺能神经元
公开(公告)号：US08492149B2
公开(公告)日：2013-07-23
申请号：US12303670
申请日：2007-06-05
申请人： Myung Soo Cho , Myung-Hwa Kim , Young-II Moon , Shin Yong Moon , Sun Kyung Oh , Hee Sun Kim , Dong-Wook Kim
发明人： Myung Soo Cho , Myung-Hwa Kim , Young-II Moon , Shin Yong Moon , Sun Kyung Oh , Hee Sun Kim , Dong-Wook Kim
IPC分类号： C12N5/00 , C12N5/02 , C12N5/071
CPC分类号： C12N5/0623 , C12N5/0619 , C12N2500/38 , C12N2500/44 , C12N2500/90 , C12N2501/115 , C12N2501/119 , C12N2501/41 , C12N2533/90
摘要： The present invention relates to a method for inducing the differentiation of neural progenitors, neurons, and dopaminergic neurons from human embryonic stem cells with high efficiency, in which neural selection can be performed by the selected media and physical methods. The invention has advantages such as higher efficiency, the effect of lowering cost and time, and maintenance of neural progenitors for a longer period of time, as compared to the known methods for inducing the differentiation into neural progenitors, neurons, and dopaminergic neurons. Accordingly, the method can stably generate cells used for treating Parkinson's disease or other nervous system diseases.
摘要翻译：本发明涉及一种以高效率从人类胚胎干细胞诱导神经祖细胞，神经元和多巴胺能神经元分化的方法，其中神经选择可以通过所选择的培养基和物理方法进行。与用于诱导分化成神经祖细胞，神经元和多巴胺能神经元的已知方法相比，本发明具有更高效率，降低成本和时间以及更长时间内神经祖细胞维持的优点。因此，该方法可以稳定地产生用于治疗帕金森病或其他神经系统疾病的细胞。

8. 发明申请

US20130101647A1 PHARMACEUTICAL COMPOSITION IN WHICH SOLUBILITY OF PARTIALLY SOLUBLE TRICYCLIC DERIVATIVE IS IMPROVED 有权
标题翻译：可改善部分可溶性三聚体衍生物的溶解性的药物组合物
公开(公告)号：US20130101647A1
公开(公告)日：2013-04-25
申请号：US13806837
申请日：2011-06-23
申请人： Myung-Hwa Kim , Kwang-Woo Chun , In-Hae Ye , Jong-Hee Choi
发明人： Myung-Hwa Kim , Kwang-Woo Chun , In-Hae Ye , Jong-Hee Choi
IPC分类号： A61K47/28
CPC分类号： A61K47/28 , A61K9/0019 , A61K9/5123 , A61K31/01 , A61K31/66
摘要： A pharmaceutical composition includes lipid nanoparticles which include two or more of a phospholipid, cholesterol, and an ionic lipid, and a tricyclic derivative, wherein the solubility of the tricyclic derivative is improved. It is possible to solubilize a partially soluble tricyclic derivative in a high concentration even without using a solubilization aid harmful to the human body, to maintain improved solubility even if water is added for the use as an injection, and to show stability even if stored for a long time, by preparing lipid nanoparticles. Therefore, the lipid nanoparticles of the present invention can be used for preparing a pharmaceutical preparation containing a partially soluble tricyclic derivative as an active ingredient.
摘要翻译：药物组合物包括包含磷脂，胆固醇和离子脂质中的两种或更多种的脂质纳米颗粒和三环衍生物，其中三环衍生物的溶解度得到改善。即使不使用对人体有害的增溶助剂，也可以高浓度溶解部分可溶性三环衍生物，即使添加水作为注射剂也能保持改善的溶解性，并且即使存储很长时间，通过制备脂质纳米粒子。因此，本发明的脂质纳米颗粒可用于制备含有部分可溶性三环衍生物作为活性成分的药物制剂。

9. 发明申请

US20110218193A1 NOVEL TRICYCLIC DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME 有权
标题翻译：新型三环衍生物或药物可接受的盐，其制备方法和含有其的药物组合物
公开(公告)号：US20110218193A1
公开(公告)日：2011-09-08
申请号：US13128030
申请日：2009-11-11
申请人： Myung-Hwa Kim , Seung-Hyun Kim , Sae-Kwang Ku , Chun-Ho Park , Bo-Young Joe , Kwang-Woo Chun , In-Hae Ye , Jong-Hee Choi , Dong-Kyu Ryu , Ji-Seon Park , Han-Chang Lee , Ji-So Choi , Young-Chul Kim
发明人： Myung-Hwa Kim , Seung-Hyun Kim , Sae-Kwang Ku , Chun-Ho Park , Bo-Young Joe , Kwang-Woo Chun , In-Hae Ye , Jong-Hee Choi , Dong-Kyu Ryu , Ji-Seon Park , Han-Chang Lee , Ji-So Choi , Young-Chul Kim
IPC分类号： A61K31/541 , C07D471/04 , A61K31/4375 , A61P35/00 , A61P25/16 , A61P25/02 , A61P25/28 , A61P25/08 , A61P25/18 , A61P19/02 , A61P19/10 , A61P9/10 , A61K31/496 , A61K31/5377
CPC分类号： C07D471/04
摘要： The present invention relates to a novel tricyclic derivative with efficient inhibitory activity against poly(ADP-ribose)polymerases (PARP) or pharmaceutically acceptable salts thereof, a preparation method thereof, and a pharmaceutical composition containing the same. The tricyclic derivative of the invention is useful for the prevention or treatment of diseases caused by excess PARP activity, especially neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic nephropathy, inflammatory diseases, osteoporosis, and cancer, by inhibiting the activity of poly(ADP-ribose)polymerases.
摘要翻译：本发明涉及对聚（ADP-核糖）聚合酶（PARP）或其药学上可接受的盐具有高效抑制活性的新型三环衍生物及其制备方法，以及含有它们的药物组合物。本发明的三环衍生物可用于预防或治疗由过量PARP活性引起的疾病，特别是神经性疼痛，神经变性疾病，心血管疾病，糖尿病性肾病，炎性疾病，骨质疏松症和癌症，通过抑制聚（ADP - 核糖）聚合酶。

10. 发明申请

US20070221862A1 Coupled Electrostatic Ion and Electron Traps for Electron Capture Dissociation - Tandem Mass Spectrometry 审中-公开
标题翻译：用于电子俘获解离的偶联静电离子和电子阱 - 串联质谱法
公开(公告)号：US20070221862A1
公开(公告)日：2007-09-27
申请号：US11676856
申请日：2007-02-20
申请人： Arthur Suits , Myung Hwa Kim , Brian D. Leskiw
发明人： Arthur Suits , Myung Hwa Kim , Brian D. Leskiw
IPC分类号： H01J49/00 , H01J27/00
CPC分类号： H01J49/4245 , H01J49/0054
摘要： A mass spectrometer employing an electrostatic ion trap and electron trap. An ion source generates a stream of ions that are directed into the mass spectrometer. The mass spectrometer includes an ion-focusing region for focusing the ions along a predetermined axis. The focused ions are injected into the electrostatic ion trap where they oscillate between two electrostatic mirror assemblies. A stream of electrons is directed into the electron trap, where the electrons interact with the ions at an interaction region between adjacent electrode assemblies of the ion trap and the electron trap. The interaction between the ions and electrons creates ions, fragments and particles of various masses that can be detected by a pick-up electrode.
摘要翻译：使用静电离子阱和电子阱的质谱仪。离子源产生被引导到质谱仪中的离子流。质谱仪包括用于沿着预定轴线聚焦离子的离子聚焦区域。将聚焦离子注入到静电离子阱中，在静电离子阱中它们在两个静电镜组件之间振荡。电子流被引导到电子陷阱中，其中电子与离子在离子阱的相邻电极组件和电子阱之间的相互作用区域相互作用。离子和电子之间的相互作用产生可以由拾取电极检测的各种质量的离子，碎片和颗粒。

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