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

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。

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：US20070036843A1

公开(公告)日：2007-02-15

申请号：US11341016

申请日：2006-01-27

申请人： Jane Hirsh ,  Roman Rariy ,  Mark Trumbore ,  Alison Fleming ,  Mark Hirsh

发明人： Jane Hirsh ,  Roman Rariy ,  Mark Trumbore ,  Alison Fleming ,  Mark Hirsh

IPC分类号： A61K9/70 ,  A61K9/22

CPC分类号： A61K31/4402 ,  A61K9/006 ,  A61K9/5026 ,  A61K31/137 ,  A61K47/585

摘要： An improved controlled release composition for non-parenteral administration of active agents and other therapeutics, particularly for oral or topical administration, has been developed. The composition is made by dispersing a complex formed of an active agent bound to an ion-exchange resin or to another form of resin or carrier, in a non-ionic non-aqueous (“NINA”) vehicle. The complexes are optionally coated with one or more layers of coating material to provide a controlled pattern of release of active agent from the carrier. Replacing the usual aqueous vehicle with a NINA vehicle, such as an oil or an ointment, allows the active agent-carrier complexes, with or without coatings, to be both orally and topically administered. The compositions can be formulated as powders, liquids, liquid suspensions, gels, capsules, soft gelatin capsules, tablets, chewable tablets, topical ointments, lotions, pourable or pumpable fluids, semisolid, crushable tablets, and unit-of-use sachets or capsules for reconstitution or direct application. The combination of multiple active agents is possible with this system, in which one or more active agents are bound to particles and one or more active agents are dissolved or dispersed in the NINA vehicle. This allows the combination of two or more active agents, which are otherwise incompatible, into a single dosage form.

摘要翻译： 已经开发了用于非肠胃外给药活性剂和其它治疗剂，特别是用于口服或局部给药的改进的控释组合物。 该组合物通过在非离子非水（“NINA”）载体中分散由与离子交换树脂结合的活性剂形成的络合物或另一种形式的树脂或载体。 复合物任选地涂覆有一层或多层涂层材料，以提供活性剂从载体中释放的受控模式。 用诸如油或软膏的NINA载体代替普通的水性载体，允许具有或不具有涂层的活性剂 - 载体复合物均经口和局部施用。 组合物可以配制成粉末，液体，液体悬浮液，凝胶，胶囊，软明胶胶囊，片剂，咀嚼片，局部软膏，洗剂，可倾倒或可泵送的液体，半固体，可压碎片剂和单位使用的小袋或胶囊 用于重组或直接应用。 该系统可以使用多种活性剂的组合，其中一种或多种活性剂与颗粒结合，一种或多种活性剂溶解或分散在NINA载体中。 这允许将两种或更多种否则不相容的活性剂组合成单一剂型。

公开(公告)号：US20050281748A1

公开(公告)日：2005-12-22

申请号：US11149867

申请日：2005-06-10

申请人： Jane Hirsh ,  Alison Fleming ,  Roman Rariy ,  Alexander Klibanov

发明人： Jane Hirsh ,  Alison Fleming ,  Roman Rariy ,  Alexander Klibanov

IPC分类号： A61K9/14 ,  A61K9/20 ,  A61K9/48 ,  A61K9/50 ,  A61K49/00

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），所述滥用威慑物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：US08449909B2

公开(公告)日：2013-05-28

申请号：US12823628

申请日：2010-06-25

申请人： Jane Hirsh ,  Alison Fleming ,  Roman Rariy ,  Alexander Kilbanov

发明人： Jane Hirsh ,  Alison Fleming ,  Roman Rariy ,  Alexander Kilbanov

IPC分类号： A61K9/54 ,  A61K9/42 ,  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），所述滥用威慑物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：US20050181050A1

公开(公告)日：2005-08-18

申请号：US11046608

申请日：2005-01-28

申请人： Jane Hirsh ,  Alison Fleming ,  Roman Rariy

发明人： Jane Hirsh ,  Alison Fleming ,  Roman Rariy

IPC分类号： A61K9/50 ,  A61K31/785 ,  A61K47/48 ,  A61K9/20 ,  A61K9/26

CPC分类号： A61K31/785 ,  A61K9/5026 ,  A61K47/585

摘要： A multiparticulate, modified release composition for oral administration has been developed. The formulation is made by complexing a drug with an ion-exchange resin in the form of small particles, typically less than 150 microns. The present invention provides novel extended release coated ion exchange particles comprising drug-resin complexes, produced by binding the salt form of the drug, that do not require impregnating agents to insure the integrity of the extended release coat. To prepare a modified release formulation, one or more of the following types of particles are formulated into a final dosage form: (a) Immediate release particles, (b) Enteric coated particles, (c) Extended release particles, (d) Enteric coated-extended release particles; and (e) Delayed release particles. The various drug-containing particles described above can be further formulated into a number of different easy-to-swallow final dosage forms including, but not limited to, a liquid suspension, gel, chewable tablet, crushable tablet, rapidly dissolving tablet, or unit of use sachet or capsule for reconstitution

摘要翻译： 已经开发了用于口服给药的多微粒，改性释放组合物。 通过将药物与通常小于150微米的小颗粒形式的离子交换树脂络合来制备该制剂。 本发明提供了新颖的延长释放包被的离子交换颗粒，其包含通过结合药物的盐形式产生的药物 - 树脂复合物，其不需要浸渍剂以确保延长释放包衣的完整性。 为了制备改性释放制剂，将下列类型的一种或多种颗粒配制成最终剂型：（a）即时释放颗粒，（b）肠溶包衣颗粒，（c）延长释放颗粒，（d）肠溶衣 - 释放颗粒; 和（e）延迟释放颗粒。 上述各种含药颗粒可以进一步配制成许多不同的易吞咽最终剂型，包括但不限于液体悬浮液，凝胶，咀嚼片，可压碎片剂，快速溶解片剂或单元 的小袋或胶囊用于重建