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1. 发明申请

US20080260819A1 SUSTAINED RELEASE COMPOSITIONS OF DRUGS 审中-公开
标题翻译：持续发布药物组合物
公开(公告)号：US20080260819A1
公开(公告)日：2008-10-23
申请号：US12112937
申请日：2008-04-30
申请人： Alison B. Fleming , Roman V. Rariy , Jane Hirsh , Alexander M. Klibanov
发明人： Alison B. Fleming , Roman V. Rariy , Jane Hirsh , Alexander M. Klibanov
IPC分类号： A61K9/52 , A61K9/00 , A61K9/26
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。

2. 发明授权

US08557291B2 Abuse-deterrent pharmaceutical compositions of opioids and other drugs 有权
标题翻译：阿片类药物和其他药物的滥用药物组合物
公开(公告)号：US08557291B2
公开(公告)日：2013-10-15
申请号：US12473073
申请日：2009-05-27
申请人： Roman V. Rariy , Alison B. Fleming , Jane Hirsh , Alexander M. Klibanov
发明人： Roman V. Rariy , Alison B. Fleming , Jane Hirsh , Alexander M. Klibanov
IPC分类号： A61K9/14 , A61K9/20 , A61K9/48
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。

3. 发明申请

US20090297617A1 ABUSE-DETERRENT PHARMACEUTICAL COMPOSITIONS OF OPIOIDS AND OTHER DRUGS 有权
标题翻译：阿片类药物和其他药物的滥用药物组合物
公开(公告)号：US20090297617A1
公开(公告)日：2009-12-03
申请号：US12473073
申请日：2009-05-27
申请人： Roman V. Rariy , Alison B. Fleming , Jane Hirsh , Alexander M. Klibanov
发明人： Roman V. Rariy , Alison B. Fleming , Jane Hirsh , Alexander M. Klibanov
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。

4. 发明申请

US20100260834A1 ABUSE-DETERRENT DRUG FORMULATIONS 有权
标题翻译：滥用药物制剂
公开(公告)号：US20100260834A1
公开(公告)日：2010-10-14
申请号：US12823628
申请日：2010-06-25
申请人： Jane C. Hirsh , Alison B. Fleming , Roman V. Rariy , Alexander M. Klibanov
发明人： Jane C. Hirsh , Alison B. Fleming , Roman V. Rariy , Alexander M. Klibanov
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。

5. 发明授权

US07771707B2 Abuse-deterrent drug formulations 有权
标题翻译：滥用威慑药物制剂
公开(公告)号：US07771707B2
公开(公告)日：2010-08-10
申请号：US11149867
申请日：2005-06-10
申请人： Jane C. Hirsh , Alison B. Fleming , Roman V. Rariy , Alexander M. Klibanov
发明人： Jane C. Hirsh , Alison B. Fleming , Roman V. Rariy , Alexander M. Klibanov
IPC分类号： A61K49/00 , A61K31/44
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 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，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损（例如通过用刀片切碎或破碎），所述滥用威慑组合物可以立即释放大部分药物，并将所得材料置于水中，嗅到或吞下去然而，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。

6. 发明授权

US07399488B2 Abuse-deterrent pharmaceutical compositions of opiods and other drugs 有权
标题翻译：阿片类药物和其他药物的滥用药物组合物
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
IPC分类号： A61K9/14 , A61K9/50
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。

7. 发明申请

US20130045960A1 Abuse-Deterrent Pharmaceutical Compositions of Opiods and Other Drugs 有权
标题翻译：鸦片和其他药物的滥用威慑药物组合物
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。

8. 发明授权

US09044398B2 Abuse-deterrent pharmaceutical compositions of opiods and other drugs 有权
标题翻译：鸦片和其他药物的滥用威慑药物组合物
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
IPC分类号： A61K9/14 , A61K9/42 , A61K31/20 , A61K31/485 , A61K9/16 , A61K47/12 , A61K9/48 , A61K9/50
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。

9. 发明申请

US20110142943A1 TAMPER-RESISTANT PHARMACEUTICAL COMPOSITIONS OF OPIODS AND OTHER DRUGS 有权
标题翻译：鸦片和其他药物的抗ANT药物组合物
公开(公告)号：US20110142943A1
公开(公告)日：2011-06-16
申请号：US12965572
申请日：2010-12-10
申请人： Roman V. Rariy , Alison B. Fleming , Jane C. Hirsh , Said Saim , Ravi K. Varanasi
发明人： Roman V. Rariy , Alison B. Fleming , Jane C. Hirsh , Said Saim , Ravi K. Varanasi
IPC分类号： A61K31/485 , A61K9/14 , A61P29/00
CPC分类号： A61K31/485 , A61K9/14 , A61K9/1617 , A61K9/1635 , A61K9/1641 , A61K9/1664 , A61K9/1694 , A61K9/4808 , A61K9/5042 , A61K47/12 , A61K47/44 , B29C70/60
摘要： Tamper-resistant pharmaceutical compositions have been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opioids. The tamper-resistant compositions retard 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：已经开发了防篡改的药物组合物，以减少不适当地施用药物，特别是诸如阿片样物质的药物的可能性。即使制剂的物理完整性受损（例如通过用刀片切碎或破碎），防篡改组合物也能延缓药物的释放，并将所得材料置于水中，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。

10. 发明授权

US08840928B2 Tamper-resistant pharmaceutical compositions of opioids and other drugs 有权
标题翻译：抗疟药物组合物的阿片样物质和其他药物
公开(公告)号：US08840928B2
公开(公告)日：2014-09-23
申请号：US12965572
申请日：2010-12-10
申请人： Roman V. Rariy , Alison B. Fleming , Jane C. Hirsh , Said Saim , Ravi K. Varanasi
发明人： Roman V. Rariy , Alison B. Fleming , Jane C. Hirsh , Said Saim , Ravi K. Varanasi
IPC分类号： A61K9/14 , A61K9/16 , A61K31/44 , A61K9/50 , A61K9/20
CPC分类号： A61K31/485 , A61K9/14 , A61K9/1617 , A61K9/1635 , A61K9/1641 , A61K9/1664 , A61K9/1694 , A61K9/4808 , A61K9/5042 , A61K47/12 , A61K47/44 , B29C70/60
摘要： Tamper-resistant pharmaceutical compositions have been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opioids. The tamper-resistant compositions retard 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：已经开发了防篡改的药物组合物，以减少不适当地施用药物，特别是诸如阿片样物质的药物的可能性。即使制剂的物理完整性受损（例如通过用刀片切碎或破碎），防篡改组合物也能延缓药物的释放，并将所得材料置于水中，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。

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