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：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：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

公开(公告)号：US20060003004A1

公开(公告)日：2006-01-05

申请号：US11192697

申请日：2005-07-29

申请人： Jane Hirsh ,  Roman Rariy ,  Michael Heffernan

发明人： Jane Hirsh ,  Roman Rariy ,  Michael Heffernan

IPC分类号： A61K9/22

CPC分类号： A61K9/4808 ,  A61K9/2054 ,  A61K9/2059 ,  A61K9/2846

摘要： A once-a-day oral milnacipran pulsatile release composition has been developed that releases the drug in spaced apart “pulses”. The dosage forms are comprised of first, second and optional third dosage units, with each dosage unit having a different drug release profile. This dosage form provides in vivo drug plasma levels characterized by Cmax below 3000 ng/ml, preferably below 2000 ng/ml, and most preferably below 1000 ng/ml. The composition provides pulsatile release of milnacipran to produce a therapeutic effect over approximately 24 hours, when administered to a patient in need, resulting in diminished incidence or decreased intensity of common milnacipran side effects such as sleep disturbance, nausea, vomiting, headache, tremulousness, anxiety, panic attacks, palpitations, urinary retention, orthostatic hypotension, diaphoresis, chest pain, rash, weight gain, back pain, constipation, vertigo, increased sweating, agitation, hot flushes, tremors, fatigue, somnolence, dyspepsia, dysoria, nervousness, dry mouth, abdominal pain, irritability, and insomnia.

摘要翻译： 已经开发了一种每天一次的口服米那普仑脉动释放组合物，其释放药物以间隔开的“脉冲”。 剂型由第一，第二和任选的第三剂量单位组成，每个剂量单位具有不同的药物释放曲线。 该剂型提供体内药物血浆水平，其特征在于低于3000ng / ml，优选低于2000ng / ml，最优选低于1000ng / ml的C max。 当给予需要的患者时，组合物提供米那普仑的脉动释放以产生约24小时的治疗效果，导致常见的米那普仑副作用的发生率降低或强度降低，例如睡眠障碍，恶心，呕吐，头痛，惊恐， 焦虑，惊恐发作，心悸，尿潴留，直立性低血压，透气，胸痛，皮疹，体重增加，背痛，便秘，眩晕，出汗增加，激动，潮红，震颤，疲劳，嗜睡，消化不良， 口干，腹痛，烦躁不安和失眠。

公开(公告)号：US20050281806A1

公开(公告)日：2005-12-22

申请号：US11147567

申请日：2005-06-08

申请人： Mark Trumbore ,  Roman Rariy ,  Mark Hirsh ,  Jane Hirsh ,  Julie Saunders

发明人： Mark Trumbore ,  Roman Rariy ,  Mark Hirsh ,  Jane Hirsh ,  Julie Saunders

IPC分类号： A61K9/00 ,  A61K9/12 ,  A61K33/18 ,  A61K33/36 ,  A61K33/38 ,  A61K36/48 ,  A61K38/46 ,  A61K38/48 ,  A61K47/44 ,  A61K35/78

CPC分类号： A61K9/0014 ,  A61K9/12 ,  A61K33/18 ,  A61K33/38 ,  A61K36/48 ,  A61K38/482 ,  A61K38/4826 ,  A61K38/4873 ,  A61K38/4886 ,  A61K47/44 ,  A61L15/34 ,  A61L15/38 ,  A61L15/48 ,  A61K2300/00

摘要： Formulations are described for the treatment by enzymatic debridement of wounds and ulcers. The formulations have a clear, transparent composition that allows for easy visualization of the wound, and are non-staining for easy clean up. These formulations can also exhibit increased enzymatic debridement activity, improved post-treatment lubricity and coating occlusivity, and stability. The formulations, optionally containing non-animal source biologics, may be in the form of lotions, aerosols to provide a spray, or a foam. A non-reactive substrate may be used as a composition carrier. A non-aqueous lotion formulation having improved enzymatic activity is provided. The non-aqueous lotion viscosity is adjusted to achieve high enzymatic activity while maintaining the application benefits of high viscosity non-aqueous lotions. The lotion formulation may be delivered in a patch.

摘要翻译： 描述了用于通过创伤和溃疡的酶清除治疗的制剂。 制剂具有清晰，透明的组合物，其允许容易地观察伤口，并且是无污染的以便于清洁。 这些制剂还可以表现出增加的酶清除活性，改善的后处理润滑性和涂层封闭性以及稳定性。 任选地含有非动物源生物制剂的制剂可以是洗剂，提供喷雾剂或泡沫剂的气溶胶的形式。 非反应性底物可以用作组合物载体。 提供了具有改善的酶活性的非水性乳液制剂。 调节非水性乳液粘度以达到高酶活性，同时保持高粘度非水性乳液的应用益处。 洗剂制剂可以在贴剂中递送。

公开(公告)号：US20080014169A1

公开(公告)日：2008-01-17

申请号：US11843158

申请日：2007-08-22

申请人： Mark Trumbore ,  Roman Rariy ,  Mark Hirsh ,  Jane Hirsh ,  Julie Saunders

发明人： Mark Trumbore ,  Roman Rariy ,  Mark Hirsh ,  Jane Hirsh ,  Julie Saunders

IPC分类号： A61K31/74 ,  A61K33/38 ,  A61K35/00 ,  A61K38/43 ,  A61P17/00

CPC分类号： A61K9/0014 ,  A61K9/12 ,  A61K33/18 ,  A61K33/38 ,  A61K36/48 ,  A61K38/482 ,  A61K38/4826 ,  A61K38/4873 ,  A61K38/4886 ,  A61K47/44 ,  A61L15/34 ,  A61L15/38 ,  A61L15/48 ,  A61K2300/00

摘要： Formulations are described for the treatment by enzymatic debridement of wounds and ulcers. The formulations have a clear, transparent composition that allows for easy visualization of the wound, and are non-staining for easy clean up. These formulations can also exhibit increased enzymatic debridement activity, improved post-treatment lubricity and coating occlusivity, and stability. The formulations, optionally containing non-animal source biologics, may be in the form of lotions, aerosols to provide a spray, or a foam. A non-reactive substrate may be used as a composition carrier. A non-aqueous lotion formulation having improved enzymatic activity is provided. The non-aqueous lotion viscosity is adjusted to achieve high enzymatic activity while maintaining the application benefits of high viscosity non-aqueous lotions. The lotion formulation may be delivered in a patch.

摘要翻译： 描述了用于通过创伤和溃疡的酶清除治疗的制剂。 制剂具有清晰，透明的组合物，其允许容易地观察伤口，并且是无污染的以便于清洁。 这些制剂还可以表现出增加的酶清除活性，改善的后处理润滑性和涂层封闭性以及稳定性。 任选地含有非动物源生物制剂的制剂可以是洗剂，提供喷雾剂或泡沫剂的气溶胶的形式。 非反应性底物可以用作组合物载体。 提供了具有改善的酶活性的非水性乳液制剂。 调节非水性乳液粘度以达到高酶活性，同时保持高粘度非水性乳液的应用益处。 洗剂制剂可以在贴剂中递送。

公开(公告)号：US20090010869A9

公开(公告)日：2009-01-08

申请号：US11843158

申请日：2007-08-22

申请人： Mark Trumbore ,  Roman Rariy ,  Mark Hirsh ,  Jane Hirsh ,  Julie Saunders

发明人： Mark Trumbore ,  Roman Rariy ,  Mark Hirsh ,  Jane Hirsh ,  Julie Saunders

IPC分类号： A61K31/74 ,  A61K33/38 ,  A61K35/00 ,  A61K38/43 ,  A61P17/00

CPC分类号： A61K9/0014 ,  A61K9/12 ,  A61K33/18 ,  A61K33/38 ,  A61K36/48 ,  A61K38/482 ,  A61K38/4826 ,  A61K38/4873 ,  A61K38/4886 ,  A61K47/44 ,  A61L15/34 ,  A61L15/38 ,  A61L15/48 ,  A61K2300/00

摘要： Formulations are described for the treatment by enzymatic debridement of wounds and ulcers. The formulations have a clear, transparent composition that allows for easy visualization of the wound, and are non-staining for easy clean up. These formulations can also exhibit increased enzymatic debridement activity, improved post-treatment lubricity and coating occlusivity, and stability. The formulations, optionally containing non-animal source biologics, may be in the form of lotions, aerosols to provide a spray, or a foam. A non-reactive substrate may be used as a composition carrier. A non-aqueous lotion formulation having improved enzymatic activity is provided. The non-aqueous lotion viscosity is adjusted to achieve high enzymatic activity while maintaining the application benefits of high viscosity non-aqueous lotions. The lotion formulation may be delivered in a patch.

摘要翻译： 描述了用于通过创伤和溃疡的酶清除治疗的制剂。 制剂具有清晰，透明的组合物，其允许容易地观察伤口，并且是无污染的以便于清洁。 这些制剂还可以表现出增加的酶清除活性，改善的后处理润滑性和涂层封闭性以及稳定性。 任选地含有非动物源生物制剂的制剂可以是洗剂，提供喷雾剂或泡沫剂的气溶胶的形式。 非反应性底物可以用作组合物载体。 提供了具有改善的酶活性的非水性乳液制剂。 调节非水性乳液粘度以达到高酶活性，同时保持高粘度非水性乳液的应用益处。 洗剂制剂可以在贴剂中递送。

公开(公告)号：US20070116757A1

公开(公告)日：2007-05-24

申请号：US11557889

申请日：2006-11-08

申请人： Roman Rariy ,  Jane Hirsh

发明人： Roman Rariy ,  Jane Hirsh

IPC分类号： A61K31/5415 ,  C07D279/24 ,  A61K9/64 ,  A61K9/20

CPC分类号： C07D279/18 ,  A61K9/1617 ,  A61K31/5415 ,  C07D265/38 ,  C07D279/20

摘要： Pharmaceutical compositions comprising a fatty acid salt, a dicarboxylic acid salt, an alkyl sulfate salt, an aryl sulfate salt or an alkyl aryl sulfonate salt of methylene blue or a derivative of methylene blue are described herein. The compositions are preferably administered orally and can be administered as tablets, soft or hard shell capsules (e.g. soft gelatin capsules), suspensions or solutions. The composition can also be formulated as a suppository or enema or rectal administration. The compositions further comprise a pharmaceutically acceptable carrier and optionally one or more pharmaceutically acceptable excipients. Suitable excipients include diluents, binders, plasticizers, lubricants, disintegrants, colorants, stabilizers, surfactants, and combinations thereof. The fatty acid salts, alkyl sulate salts, aryl sulfate salts or alkyl aryl sulfonate salts can be co-mixed or co-melted with one or more fatty acids to make more hydrophobic compositions, which may result in less staining formulations. The compositions can be formulated for immediate release, controlled release such as extended release, delayed release, and pulsatile release, or combinations thereof. In one embodiment, the derivative of methylene blue is methylene dodecylsulfate.

摘要翻译： 本文描述了包含脂肪酸盐，二羧酸盐，烷基硫酸盐，芳基硫酸盐或亚甲基蓝或亚甲基衍生物的烷基芳基磺酸盐的药物组合物。 组合物优选口服施用，并且可以片剂，软或硬壳胶囊（例如软明胶胶囊），悬浮液或溶液给药。 组合物也可以配制成栓剂或灌肠剂或直肠给药。 组合物还包含药学上可接受的载体和任选的一种或多种药学上可接受的赋形剂。 合适的赋形剂包括稀释剂，粘合剂，增塑剂，润滑剂，崩解剂，着色剂，稳定剂，表面活性剂及其组合。 脂肪酸盐，烷基磺酸盐，芳基硫酸盐或烷基芳基磺酸盐可以与一种或多种脂肪酸共混或共熔，以制备更疏水的组合物，这可能导致较少的染色制剂。 组合物可以配制成立即释放，控制释放，例如延长释放，延迟释放和脉动释放，或其组合。 在一个实施方案中，亚甲基蓝的衍生物是十二烷基硫酸亚甲酯。

公开(公告)号：US20060024366A1

公开(公告)日：2006-02-02

申请号：US11192885

申请日：2005-07-29

申请人： Jane Hirsh ,  Roman Rariy ,  Shubha Chungi ,  Srinivas Rao ,  Michael Heffernan

发明人： Jane Hirsh ,  Roman Rariy ,  Shubha Chungi ,  Srinivas Rao ,  Michael Heffernan

IPC分类号： A61K9/22

CPC分类号： A61K9/2054 ,  A61K9/2846

摘要： A once-a-day oral milnacipran modified release formulation has been developed. The formulation comprises an extended release dosage unit (optionally containing the immediate release portion) coated with delayed release coating. The milnacipran composition, when administered orally, first passes through the stomach releasing from zero to less than 10% of the total milnacipran dose and then enters the intestines where drug is released slowly over an extended period of time. The release profile is characterized by a 0.05-4 hours lag time period during which less than 10% of the total milnacipran dose is released followed by a slow or extended release of the remaining drug over a defined period of time. The composition provides in vivo drug plasma levels characterized by Tmax at 4-10 hours and an approximately linear drop-off thereafter and Cmax below 3000 ng/ml, preferably below 2000 ng/ml, and most preferably below 1000 ng/ml. The composition provides a therapeutic effect over approximately 24 hours, when administered to a patient in need, resulting in diminished incidence or decreased intensity of common milnacipran side effects such as sleep disturbance, nausea, vomiting, headache, tremulousness, anxiety, panic attacks, palpitations, urinary retention, orthostatic hypotension, diaphoresis, chest pain, rash, weight gain, back pain, constipation, vertigo, increased sweating, agitation, hot flushes, tremors, fatigue, somnolence, dyspepsia, dysoria, nervousness, dry mouth, abdominal pain, irritability, and insomnia.

摘要翻译： 已经开发了一天一次的口服米那普仑改性释放制剂。 该制剂包含用延迟释放包衣涂覆的延长释放剂量单位（任选地含有速释部分）。 当口服给药时，米那普仑组合物首先通过胃从零释放至总的米那普仑剂量的10％，然后进入肠道，药物在较长时间内缓慢释放。 释放曲线的特征在于0.05-4小时的滞后时间，在此期间，释放总的米那普仑总量的不到10％，然后在规定的时间段内缓慢或延长释放剩余的药物。 该组合物在4-10小时时提供特征为T max max的体内药物血浆水平，此后大约线性下降，低于3000ng / ml，优选低于 2000ng / ml，最优选低于1000ng / ml。 当给予需要的患者时，该组合物在约24小时内提供治疗效果，导致常见的米那普仑副作用的发生率降低或强度降低，例如睡眠障碍，恶心，呕吐，头痛，惊恐，焦虑，惊恐发作，心悸 ，尿潴留，直立性低血压，尿频，胸痛，皮疹，体重增加，背痛，便秘，眩晕，出汗增加，激动，潮红，震颤，疲劳，嗜睡，消化不良，呕吐，紧张，口干，腹痛， 烦躁不安和失眠。