-
公开(公告)号：US20130045960A1
公开(公告)日：2013-02-21
申请号：US13551455
申请日：2012-07-17
申请人： Jane Hirsh , Alexander M. Klibanov , Timothy M. Swager , Stephen L. Buchwald , Whe Yong Lo , Alison Fleming , Roman V. Rariy
发明人： Jane Hirsh , Alexander M. Klibanov , Timothy M. Swager , Stephen L. Buchwald , Whe Yong Lo , Alison Fleming , Roman V. Rariy
IPC分类号： A61K31/555 , A61K31/485 , C07D489/08 , A61P25/36 , C07F3/06
CPC分类号： A61K31/485 , A61K9/145 , A61K9/1617 , A61K9/1682 , A61K9/1694 , A61K9/4858 , A61K9/50 , A61K9/5052 , A61K9/5084 , A61K31/20 , A61K47/12
摘要： An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opiods. In the preferred embodiment, a drug is modified to increase its lipophilicity. In preferred embodiments the modified drug is homogeneously dispersed within microparticles composed of a material that is either slowly soluble or not soluble in water. The abuse-deterrent composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is broken down or dissolved gradually within the GI tract by a combination of enzymatic degradation, surfactant action of bile acids, and mechanical erosion.
摘要翻译： 已经开发了一种滥用威慑药物组合物，以减少药物不当管理的可能性，特别是诸如阿片类药物。 在优选的实施方案中，修饰药物以增加其亲油性。 在优选实施方案中，改性药物均匀地分散在由缓慢溶解或不溶于水的材料组成的微粒内。 即使制剂的物理完整性受到损害（例如通过用刀片切碎或破碎）并且将所得材料置于水中，嗅到或吞咽，滥用威慑组合物也会延缓释放药物。 然而，当按照指导施用时，通过酶降解，胆汁酸的表面活性作用和机械侵蚀的组合，组合物被分解或逐渐溶解在胃肠道内，药物从组合物中缓慢释放。
-
公开(公告)号：US09044398B2
公开(公告)日：2015-06-02
申请号：US13551455
申请日：2012-07-17
申请人： Jane Hirsh , Alexander M. Klibanov , Timothy M. Swager , Stephen L. Buchwald , Whe Yong Lo , Alison Fleming , Roman V. Rariy
发明人： Jane Hirsh , Alexander M. Klibanov , Timothy M. Swager , Stephen L. Buchwald , Whe Yong Lo , Alison Fleming , Roman V. Rariy
CPC分类号： A61K31/485 , A61K9/145 , A61K9/1617 , A61K9/1682 , A61K9/1694 , A61K9/4858 , A61K9/50 , A61K9/5052 , A61K9/5084 , A61K31/20 , A61K47/12
摘要： An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opiods. In the preferred embodiment, a drug is modified to increase its lipophilicity. In preferred embodiments the modified drug is homogeneously dispersed within microparticles composed of a material that is either slowly soluble or not soluble in water. The abuse-deterrent composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is broken down or dissolved gradually within the GI tract by a combination of enzymatic degradation, surfactant action of bile acids, and mechanical erosion.
摘要翻译： 已经开发了一种滥用威慑药物组合物，以减少药物不当管理的可能性，特别是诸如阿片类药物。 在优选的实施方案中，修饰药物以增加其亲油性。 在优选实施方案中，改性药物均匀地分散在由缓慢溶解或不溶于水的材料组成的微粒内。 即使制剂的物理完整性受到损害（例如通过用刀片切碎或破碎）并且将所得材料置于水中，嗅到或吞咽，滥用威慑组合物也会延缓释放药物。 然而，当按照指导给药时，由于组合物通过酶降解，胆汁酸的表面活性作用和机械侵蚀的组合被分解或逐渐溶解在胃肠道内，药物从组合物中缓慢释放。
-
公开(公告)号：US07399488B2
公开(公告)日：2008-07-15
申请号：US10614866
申请日：2003-07-07
申请人： Jane Hirsh , Alexander M. Kibanov , Timothy M. Swager , Stephen L. Buchwald , Whe Yong Lo , Alison B. Fleming , Roman V. Rariy
发明人： Jane Hirsh , Alexander M. Kibanov , Timothy M. Swager , Stephen L. Buchwald , Whe Yong Lo , Alison B. Fleming , Roman V. Rariy
CPC分类号： A61K31/485 , A61K9/145 , A61K9/1617 , A61K9/1682 , A61K9/1694 , A61K9/4858 , A61K9/50 , A61K9/5052 , A61K9/5084 , A61K31/20 , A61K47/12
摘要： An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opiods. In the preferred embodiment, a drug is modified to increase its lipophilicity. In preferred embodiments the modified drug is homogeneously dispersed within microparticles composed of a material that is either slowly soluble or not soluble in water. In some embodiments the drug containing microparticles or drug particles are coated with one or more coating layers, where at least one coating is water insoluble and preferably organic solvent insoluble, but enzymatically degradable by enzymes present in the human gastrointestinal tract. The abuse-deterrent composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is broken down or dissolved gradually within the GI tract by a combination of enzymatic degradation, surfactant action of bile acids, and mechanical erosion.
摘要翻译： 已经开发了一种滥用威慑药物组合物，以减少药物不当管理的可能性，特别是诸如阿片类药物。 在优选的实施方案中，修饰药物以增加其亲油性。 在优选实施方案中，改性药物均匀地分散在由缓慢溶解或不溶于水的材料组成的微粒内。 在一些实施方案中，含有微粒或药物颗粒的药物涂覆有一个或多个涂层，其中至少一个涂层是水不溶性的，优选有机溶剂不溶，但是通过存在于人胃肠道中的酶可酶促降解。 即使制剂的物理完整性受到损害（例如通过用刀片切碎或破碎）并且将所得材料置于水中，嗅到或吞咽，滥用威慑组合物也会延缓释放药物。 然而，当按照指导给药时，由于组合物通过酶降解，胆汁酸的表面活性作用和机械侵蚀的组合被分解或逐渐溶解在胃肠道内，药物从组合物中缓慢释放。
-
公开(公告)号：US07309799B2
公开(公告)日：2007-12-18
申请号：US11097466
申请日：2005-04-01
IPC分类号： C07C211/00 , C07C231/00
CPC分类号： C07D209/48 , C07D307/00
摘要： One aspect of the present invention relates to methods for synthesizing milnacipran or congeners thereof. Another aspect of the present invention relates to asymmetric methods for synthesizing enantiomerically enriched milnacipran or congeners thereof. The present invention also relates to methods for synthesizing intermediates useful in the non-asymmetric or asymmetric methods for synthesizing enantiomerically enriched milnacipran or congeners thereof.
摘要翻译： 本发明的一个方面涉及合成米那普仑或其同系物的方法。 本发明的另一方面涉及用于合成对映体富集的米那普仑或其同系物的不对称方法。 本发明还涉及用于合成对映体富集的米那普仑或其同系物的非对称或非对称方法中的中间体的方法。
-
公开(公告)号：US07038085B2
公开(公告)日：2006-05-02
申请号：US10691465
申请日：2003-10-22
IPC分类号： C07C233/05 , A61K31/165
CPC分类号： C07C237/24 , C07B2200/07 , C07C2601/02
摘要： The present invention relates generally to the enantiomers of para-hydroxy-milnacipran or congeners thereof. Biological assays revealed that racemic para-hydroxy-milnacipran is approximately equipotent in inhibiting serotonin and norepinephrine uptake (IC50=28.6 nM for norepinephrine, IC50=21.7 nM for serotonin). Interestingly, (+)-para-hydroxy-milnacipran is a more potent inhibitor of norepinephrine uptake than serotonin uptake (IC50=10.3 nM for norepinephrine, IC50=22 nM for serotonin). In contrast, (−)-para-hydroxy-milnacipran is a more potent inhibitor of serotonin uptake compared to norepinephrin uptake (IC50=88.5 nM for norepinephrine, IC50=40.3 nM for serotonin). The invention also relates to salts and prodrug forms of the aforementioned compounds. In certain embodiments, the compounds of the present invention and a pharmaceutically acceptable excipient are combined to prepare a formulation for administration to a patient. Finally, the present invention relates to methods of treating mammals suffering from various afflictions, e.g., depression, chronic pain, or fibromyalgia, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of the present invention.
摘要翻译： 本发明一般涉及对羟基 - 米那普兰或其同系物的对映异构体。 生物测定显示外消旋的对羟基 - 米那普仑在抑制5-羟色胺和去甲肾上腺素摄取方面几乎是等量的（对于5-羟色胺，对于去甲肾上腺素为IC 50 N = 28.7nM，对于5-羟色胺为131.7nM） 。 有趣的是，（+） - 对羟基 - 米那普仑是去甲肾上腺素摄取的更有效的抑制剂，而不是5-羟色胺摄取（去甲肾上腺素（IC 50）= 22nM 用于5-羟色胺）。 相比之下，与去甲肾上腺素摄取相比，（ - ） - 对羟基 - 米那普仑是一种更有效的5-羟色胺摄取抑制剂，对于去甲肾上腺素，IC 50 <= 50> = 对于5-羟色胺为40.3nM）。 本发明还涉及上述化合物的盐和前药形式。 在某些实施方案中，将本发明的化合物和药学上可接受的赋形剂混合以制备用于给予患者的制剂。 最后，本发明涉及治疗患有各种痛苦，例如抑郁症，慢性疼痛或纤维肌痛的哺乳动物的方法，包括向有需要的哺乳动物施用治疗有效量的本发明化合物。
-
公开(公告)号：US20080260819A1
公开(公告)日：2008-10-23
申请号：US12112937
申请日：2008-04-30
CPC分类号： A61K31/485 , A61K9/145 , A61K9/1617 , A61K9/1682 , A61K9/1694 , A61K9/4858 , A61K9/50 , A61K9/5052 , A61K9/5084 , A61K31/20 , A61K47/12
摘要： A sustained release pharmaceutical composition has been developed. The composition resists dose dumping when broken, crushed or chewed, which enhances the safety of the dosage form should it be accidentally or intentionally physically compromised. In the preferred embodiment, a drug is modified to increase its lipophilicity. In preferred embodiments the modified drug is homogeneously dispersed within microparticles composed of a material that is either slowly soluble or not soluble in water. In some embodiments the drug containing microparticles coated with one or more coating layers. The sustained release composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chewing or crushing) and the resulting material is placed in 0.1N HCl. However, when administered as directed, the drug is slowly released from the composition as the composition is broken down or dissolved gradually within the GI tract by a combination of diffusion, surfactant action of bile acids, mechanical erosion, and in some embodiments, enzymatic degradation.
摘要翻译： 持续释放的药物组合物已被开发出来。 当破碎，粉碎或咀嚼时，组合物抵抗剂量倾倒，如果意外或故意身体受损，则可提高剂型的安全性。 在优选的实施方案中，修饰药物以增加其亲油性。 在优选实施方案中，改性药物均匀地分散在由缓慢溶解或不溶于水的材料组成的微粒内。 在一些实施方案中，含有涂覆有一个或多个涂层的微粒的药物。 即使制剂的物理完整性受损（例如通过咀嚼或破碎），并将所得材料置于0.1N HCl中，持续释放组合物延缓了药物的释放。 然而，当按照指导施用时，当组合物通过扩散，胆汁酸的表面活性作用，机械侵蚀，以及在一些实施方案中的酶降解的组合被分解或逐渐溶解在胃肠道内时，药物缓慢地从组合物中释放 。
-
7.发明授权公开(公告)号：US08557291B2
公开(公告)日：2013-10-15
申请号：US12473073
申请日：2009-05-27
CPC分类号： A61K47/46 , A61K9/1617 , A61K9/5026 , A61K31/485 , A61K45/06 , A61K47/12
摘要： An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opioids. In a preferred embodiment, a drug is modified to increase its lipophilicity. In some embodiments the modified drug is homogeneously dispersed within spherical microparticles composed of a material that is either slowly soluble or not soluble in water. In some embodiments the drug containing microparticles or drug particles are coated with one or more coating layers, where at least one coating is water insoluble and/or organic solvent insoluble. The abuse-deterrent composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is passes through the GI tract.
摘要翻译： 已经开发了一种滥用威慑药物组合物，以减少药物不当管理的可能性，特别是阿片样物质等药物。 在优选的实施方案中，修饰药物以增加其亲油性。 在一些实施方案中，改性药物均匀地分散在由缓慢溶解或不溶于水的材料组成的球形微粒内。 在一些实施方案中，含有微粒或药物颗粒的药物涂覆有一个或多个涂层，其中至少一种涂层是不溶于水的和/或有机溶剂不溶的。 即使制剂的物理完整性受到损害（例如通过用刀片切碎或破碎）并且将所得材料置于水中，嗅到或吞咽，滥用威慑组合物也会延缓释放药物。 然而，当按照指导给药时，当组合物通过胃肠道时，药物从组合物缓慢释放。
-
8.发明申请公开(公告)号：US20090297617A1
公开(公告)日：2009-12-03
申请号：US12473073
申请日：2009-05-27
IPC分类号： A61K9/50 , A61K31/485
CPC分类号： A61K47/46 , A61K9/1617 , A61K9/5026 , A61K31/485 , A61K45/06 , A61K47/12
摘要： An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opioids. In a preferred embodiment, a drug is modified to increase its lipophilicity. In some embodiments the modified drug is homogeneously dispersed within spherical microparticles composed of a material that is either slowly soluble or not soluble in water. In some embodiments the drug containing microparticles or drug particles are coated with one or more coating layers, where at least one coating is water insoluble and/or organic solvent insoluble. The abuse-deterrent composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is passes through the GI tract.
摘要翻译： 已经开发了一种滥用威慑药物组合物，以减少药物不当管理的可能性，特别是阿片样物质等药物。 在优选的实施方案中，修饰药物以增加其亲油性。 在一些实施方案中，改性药物均匀地分散在由缓慢溶解或不溶于水的材料组成的球形微粒内。 在一些实施方案中，含有微粒或药物颗粒的药物涂覆有一个或多个涂层，其中至少一种涂层是不溶于水的和/或有机溶剂不溶的。 即使制剂的物理完整性受损（例如通过用刀片切碎或破碎），所述滥用威慑组合物也会延缓药物的释放，并将所得物质置于水中，嗅到或吞咽。 然而，当按照指导给药时，当组合物通过胃肠道时，药物从组合物缓慢释放。
-
9.发明申请公开(公告)号：US20080199530A1
公开(公告)日：2008-08-21
申请号：US12112993
申请日：2008-04-30
申请人： Jane Hirsh , Alison Fleming , Roman V. Rariy
发明人： Jane Hirsh , Alison Fleming , Roman V. Rariy
IPC分类号： A61K9/16
CPC分类号： A61K31/485 , A61K9/145 , A61K9/1617 , A61K9/1682 , A61K9/1694 , A61K9/4858 , A61K9/50 , A61K9/5052 , A61K9/5084 , A61K31/20 , A61K47/12
摘要： An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opiods. In the preferred embodiment, a drug is modified to increase its lipophilicity. In preferred embodiments the modified drug is homogeneously dispersed within microparticles composed of a material that is either slowly soluble or not soluble in water. In some embodiments the drug containing microparticles or drug particles are coated with one or more coating layers, where at least one coating is water insoluble and preferably organic solvent insoluble, but enzymatically degradable by enzymes present in the human gastrointestinal tract. The abuse-deterrent composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is broken down or dissolved gradually within the GI tract by a combination of enzymatic degradation, surfactant action of bile acids, and mechanical erosion.
摘要翻译： 已经开发了一种滥用威慑药物组合物，以减少药物不当管理的可能性，特别是诸如阿片类药物。 在优选的实施方案中，修饰药物以增加其亲油性。 在优选实施方案中，改性药物均匀地分散在由缓慢溶解或不溶于水的材料组成的微粒内。 在一些实施方案中，含有微粒或药物颗粒的药物涂覆有一个或多个涂层，其中至少一个涂层是水不溶性的，优选有机溶剂不溶，但是通过存在于人胃肠道中的酶可酶促降解。 即使制剂的物理完整性受到损害（例如通过用刀片切碎或破碎）并且将所得材料置于水中，嗅到或吞咽，滥用威慑组合物也会延缓释放药物。 然而，当按照指导给药时，由于组合物通过酶降解，胆汁酸的表面活性作用和机械侵蚀的组合被分解或逐渐溶解在胃肠道内，药物从组合物中缓慢释放。
-
公开(公告)号：US20100260834A1
公开(公告)日：2010-10-14
申请号：US12823628
申请日：2010-06-25
IPC分类号： A61K9/50 , A61K31/485 , A61K9/48 , A61P25/04
CPC分类号： A61K31/485 , A61K9/0053 , A61K9/145 , A61K9/148 , A61K9/1617 , A61K9/1664 , A61K9/2013 , A61K9/4808 , A61K9/4858 , A61K9/5015 , A61K9/5042 , A61K31/13 , A61K31/20 , A61K45/06 , A61K47/12 , A61K2300/00
摘要： An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opiods. In the preferred embodiment, the drug is modified to increase its lipophilicity by forming a salt between the drug and one or more fatty acids wherein the concentration of the one or more fatty acids is one to 15 times the molar amount of the active agent, preferably two to ten times the molar amount of the active agent. In one embodiment the modified drug is homogeneously dispersed within microparticles composed of a material that is either slowly soluble or not soluble in water. In some embodiments the drug containing microparticles or drug particles are coated with one or more coating layers, where at least one coating is water insoluble and preferably organic solvent insoluble. The abuse-deterrent composition prevents the immediate release of a substantial portion of drag, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is broken down or dissolved gradually within the GI tract by a combination of enzymatic degradation, surfactant action of bile acids, and mechanical erosion.
摘要翻译： 已经开发了一种滥用威慑药物组合物，以减少药物不当管理的可能性，特别是诸如阿片类药物。 在优选的实施方案中，通过在药物和一种或多种脂肪酸之间形成盐，来修饰药物以增加其亲油性，其中一种或多种脂肪酸的浓度是活性剂的摩尔量的1至15倍 活性剂摩尔量的2〜10倍。 在一个实施方案中，改性药物均匀地分散在由缓慢溶解或不溶于水的材料组成的微粒内。 在一些实施方案中，含有微粒或药物颗粒的药物涂覆有一个或多个涂层，其中至少一个涂层是水不溶性的，优选有机溶剂不溶。 即使制剂的物理完整性受到损害（例如通过用刀片切碎或破碎）并且将所得材料放置在水中，嗅到或or or or or or or or or or or or or or or or or or or or or or or or or or 吞下去 然而，当按照指导给药时，由于组合物通过酶降解，胆汁酸的表面活性作用和机械侵蚀的组合被分解或逐渐溶解在胃肠道内，药物从组合物中缓慢释放。
-
-
-
-
-
-
-
-
-
搜索结果
22 条记录 (耗时 0.035 秒)
