CN100444830C - 多颗粒改进释放组合物 - Google Patents
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Abstract
本发明涉及一种在起作用过程中以脉冲或双峰方式释放活性组分的多颗粒改进释放组合物。该多颗粒改进释放组合物包括即时释放的成分和改进释放的成分；所述的即时释放成分包括第一种含有活性组分的颗粒群且所述的改进释放成分包括第二种含有活性组分的用控释包衣层包衣的颗粒群；其中即时释放和改进释放成分联用可在起作用的过程中以脉冲或双峰方式释放活性组分。本发明还涉及一种含有这类多颗粒改进释放组合物的固体口服剂型。由该多颗粒改进释放组合物达到的血浆分布有利于降低患者对所述活性组分的耐药性并通过减少给药频率而增加患者的配合性。
Description
本发明涉及一种多颗粒改进释放组合物。特别地，本发明涉及一种在起作用过程中以搏动方式释放活性组分的多颗粒改进释放组合物。本发明进一步涉及含有这类多颗粒控释组合物的固体口服剂型。
可以将与给予药物化合物相关的血浆分布描述为“搏动分布”，其中观察到了以低浓度谷值分散的高浓度活性组分的脉冲。将包括两个峰的搏动分布描述为“双峰”。类似地，可以将在给药时产生这类分布的组合物或剂型称作具有“脉冲释放”的活性组分。
按照定期间隔给予即时释放(IR)剂型的常规频率剂量方案一般产生搏动血浆分布。在这种情况中，在连续给药时间点之间发展有峰谷浓度(低药物浓度区)且给予各IR剂量后观察到了血药浓度中的峰值。这类剂量方案(及其产生的搏动血浆分布)具有与它们相关的特定药理作用和治疗作用。例如，认为各峰之间活性组分血浆浓度下降所产生的消除期是构成降低或防止患者对各种类型药物耐药性的因素。
许多控释药物制剂的目的在于产生药物化合物的零级释放。实际上，这些制剂通常的特殊目的在于将与常规频率的剂量方案相关的血药浓度的峰-谷变化降低到最低限度。然而，实质上搏动系统中的某些治疗和药理作用可能作为由零级释放药物转运系统产生的恒定或近似恒定的血浆浓度的结果而失去或降低。因此，理想的是改进释放组合物或制剂基本上可模拟释放频率IR剂量方案的剂量、同时减少对频繁给药的需求。
可在患者中产生耐药性的一个药物的典型实例是哌醋甲酯。哌醋甲酯(或α-苯基-2-哌啶乙酸甲酯)是一种影响中枢神经系统和呼吸系统的刺激剂并且主要用于治疗注意力不集中的疾病。在从胃肠道(GTT)吸收后，药物作用在口服给予常用IR片后持续3-6小时或在口服给予延长释放制剂后持续达约8小时。总剂量一般在5-30mg/天的范围，在有些情况中剂量可以升高至60mg/天。在常规剂量方案中，每日给予两次哌醋甲酯，一般在早餐前给予一次剂量并在中餐前给予第二次剂量。最终的每日剂量优选在就寝前几小时给予。与哌醋甲酯疗法相关的不良反应包括失眠症和患者产生耐药性。
WO 98/14168(Alza Corp.)教导了以持续和不断上升的比例给予哌醋甲酯的剂型和方法。所公开的剂型包括多个用可变量控制释放速率的物质包衣的珠，这些珠中包括含有增加量的活性组分的水凝胶基质。可以对活性组分的剂量与包衣层的数量和厚度的适当组成进行选择以便得到升高的释放分布，其中活性组分的血浆浓度在给定的时间期限内持续增加。与本发明相反，WO 98/14168的目的在于提供一种特别可以避免与使用即时释放剂型的常规疗法相关的不稳定的血药浓度(以峰和谷为特征)的剂型。
WO97/03672(Chiroscience Ltd.)公开了当给予外消旋混合物形式或单一异构体形式(诸如RR d-苏式对映体)的哌醋甲酯时，它表现出了治疗作用。此外，WO97/03672(Chiroscience Ltd.)公开了含有dtmp的缓释制剂。该文献教导了含有包衣层的组合物的用途，dtmp通过所述的包衣层达到延缓释放和在至少8小时期限内达到至少50％Cmax(活性组分)血清浓度的目的。因此，该制剂不会以搏动方式释放活性组分。
Shah等在《控释杂志》(J.Cont.Rel.)(1989)9：169-175中公开了将某些类型的羟丙基甲基纤维素醚类与治疗剂一起压制成的固体剂型可以产生双峰释放分布。然而，应注意尽管从一个供应商处购得的聚合物可产生双峰分布，但是与从不同来源获得的产品规格几乎相同的聚合物却产生非双峰型释放分布。
Giunchedi等在《国际药理学杂志》(Int.J.Pharm)77：177-181中公开了亲水性基质多剂量制剂在搏动释放酮基布洛芬中的用途。Giunchedi等教导了在给药后(血浆半衰期1-3小时)酮基布洛芬快速从血液中消除且对于某些治疗来说连续搏动给药比恒定释放给药更为有利。所公开的多剂量制剂包括4种置于胶囊中的相同亲水骨架片。尽管体内研究证实了血浆分布中的两个峰，但是没有充分确定消除期且峰值与谷值血浆浓度之间的变化形式很小。
Conte等在《药物转运与制药工业》(Drug Dev.Ind.Pharm.)(1989)15：2583-2596和EP 0 274 734(Pharmidea Srl)中教导了三层片在以连续脉冲方式转运布洛芬中的用途。这种三层片由含有活性组分的第一层、插入第一层与含有另外量活性组分的第三层之间的半透性物质的屏障层(第二层)组成。屏障层和第三层隐藏在不透性套层中。第一层在与溶解用液体接触时溶解，而第三层仅在溶解后屏障层破裂后生成。在这类片剂中，第一部分活性组分必须即刻释放。该手段还需要第一层与第三层之间必备的半透性层以便控制两部分活性组分转运的相对速率。另外，半透性层的破裂导致第二部分活性组分不受控制的排出，这是不理想的。
US 5,158,777(E.R.Squibb & Sons Inc.)中公开了在混有另外在给药后即时释放的卡托普利的包肠溶衣或包缓释衣的pH稳定的药芯内包括卡托普利的制剂。为了形成pH稳定的药芯，可以单独使用或与缓冲剂一起使用诸如乙二胺四乙酸二钠这样的螯合剂或诸如聚山梨醇酯80这样的表面活性剂。该组合物含有可在口服给药后获得即时释放量的卡托普利和在结肠内获得释放的另外量的pH稳定的卡托普利。
US 4,728,512、US 4,794,001和US 4,904,476(American HomeProducts Corp.)涉及可产生三种不同释放效果的制剂。该制剂包括三组含有活性药物物质的球状体：第一组球状体未包衣且在摄取时快速崩解而释放初始剂量的药物物质；第二组球状体包有pH敏感性包衣层以便提供第二种剂量；而第三组球形体包有pH依赖性包衣层以便提供第三种剂量。将该制剂设计成可预先经全身广泛代谢或具有相对较短的消除半衰期的产生反复释放的药物物质。
美国专利号5,837,284(Mehta等)公开了含有即时释放和延缓释放颗粒的哌醋甲酯剂型。延缓释放通过应用混有某些填料的甲基丙烯酸铵pH依赖性聚合物而产生。
因此，本发明的一个目的是提供一种含有活性组分的多颗粒改进释放组合物，在起作用过程中它可产生与通过依次给予两种或多种IR剂型所产生的血浆分布相类似的血浆分布。
本发明的另一个目的是提供一种在起作用过程中以一种搏动方式释放活性组分的多颗粒改进释放组合物。
本发明的另一个目的是提供一种主要模拟通过依次给予两种或多种IR剂型所产生的药理作用和治疗作用的多颗粒改进释放组合物。
本发明的另一个目的是提供一种基本上降低或消除患者对组合物中活性组分产生耐药性的多颗粒改进释放组合物。
本发明的另一个目的是提供一种多颗粒改进释放组合物，其中第一部分活性组分在给药时即刻释放而第二部分活性组分在初步延期后以一种双峰形式快速释放。
本发明的另一个目的是提供一种能够以双峰或多峰形式释放活性组分的多颗粒改进释放组合物，其中第一部分活性组分即刻释放或在延缓期限后释放以便形成脉冲药物释放而活性组分的另一部分或多部分各自在相应的延滞时间后释放以便形成另外脉冲形式的药物释放。
本发明的另一个目的是提供包括本发明多颗粒改进释放组合物的固体口服剂型。
本发明的其它目的包括提供每日一次的哌醋甲酯剂型和以给予这类剂型为基础治疗注意力不集中疾病的方法，其中在起作用过程中所述的组合物可产生与通过依次给予两种即时释放剂型所产生的血浆分布相类似的血浆分布。
通过多颗粒改进释放组合物可以实现上述目的，所述的组合物具有包括第一部分含活性组分的颗粒群的第一种成分和包括第二部分含活性组分的颗粒群的第二种成分。在第一种成分和第二种成分中包含的活性组分可以相同或不同并将第二种成分中含活性组分的颗粒用改进释放的包衣层包衣。另一方面或另外，第二部分含活性组分的颗粒群进一步“包括”改进释放的基质物质。在口服转运后，在起作用过程中该组合物以一种搏动方式释放活性组分或多种活性组分。
在本发明多颗粒改进释放组合物的一个优选的实施方案中，第一种成分是即时释放成分。
施用在第二部分含活性组分的颗粒群上的改进释放包衣层在从第一部分含活性组分的颗粒群中释放活性组分与从第二部分含活性组分的颗粒群中释放活性组分之间产生延滞时间。类似地，第二部分含活性组分的颗粒群中改进释放基质物质的存在使得从第一部分含活性组分的颗粒群中释放活性组分与从第二部分含活性组分的颗粒群中释放活性组分之间产生延滞时间。可以通过改变所用的改进释放包衣层的组成和/或量和/或改变改进释放基质物质的组成和/或量来改变所述延滞时间的期限。因此，可以将延滞时间的期限用来模拟所需的血浆分布。
因为在给药时由多颗粒改进释放组合物产生的血浆分布基本上类似于通过依次给予两种或多种IR剂型所产生的血浆分布，所以特别将本发明的多颗粒控释组合物用于给予可能对患者产生耐药性疑难问题的活性组分。这种多颗粒改进释放组合物由此有利于减少患者对该组合物中活性组分产生的耐药性或将其降低到最低限度。
在本发明的一个优选的实施方案中，所述的活性组分是哌醋甲酯且所述的组合物在起作用过程中以一种双峰或脉冲方式释放活性组分。例如，在典型的哌醋甲酯治疗方案中，这类组合物在起作用过程中产生基本上与通过依次给予两种IR剂量所获得的血浆分布相类似的血浆分布。
本发明还提供了包括本发明组合物的固体口服剂型。
本发明进一步提供了一种根据应用所述活性组分的治疗方法的需要治疗动物、特别是人的方法，该方法包括给予治疗有效量的本发明组合物或固体口服剂型的步骤以便提供脉冲或双峰给药形式的活性组分。
本发明的优点包括减少常规多IR剂量方案所需的给药频率，同时仍然维持来源于搏动血浆分布的有益效果。这种给药频率的减少特别有利于儿童病例，即它可消除对患者不利和为难的在校期间给药的需求。鉴于患者的配合性，另外有利的是拥有一种可以按照减少频率给药的制剂。通过应用本发明而可能减少剂量频率这一事实会通过减少保健工作者在给药时所花费的时间来降低保健成本。就哌醋甲酯和其它受控物质而言，每日一次制剂的应用(取代多IR剂量)减少或消除了对去学校或其它机构前储存受控物质的需要。
附图1表明了将下列三种制剂对人体志愿者口服给药后的哌醋甲酯的血浆分布：A-20mg哌醋甲酯制剂，它具有包括含总计10mg哌醋甲酯的颗粒的即时释放成分(根据表1(ii))和包括含总计10mg哌醋甲酯的颗粒的改进释放成分(根据表2(viii)；IR颗粒包有增加至30％重量的包衣层)；B-20mg哌醋甲酯制剂，它具有包括含总计10mg哌醋甲酯的颗粒的即时释放成分(根据表1(ii))和包括含总计10mg哌醋甲酯的颗粒的改进释放成分(根据表2(vii)；IR颗粒包有增加至30％重量的包衣层)；和对照组-在0时和4小时时给予的两个剂量的10mg Ritalin
Hydrochloride(IR)片(总计给予20mg哌醋甲酯)。
本文所用的术语“颗粒”指的是特征在于以与大小、形状或形态无关的分散粒子、丸粒、珠或颗粒形式存在的物质状态。本文所用的术语“多颗粒”指的是与大小、形状或形态无关的多个分散或聚集的粒子、丸粒、珠、颗粒或其混合物。
与本发明组合物或包衣层或包衣材料或上下文中任意其它部分中所用的物质相关的本文所用的术语“改进释放”指的是并非即时释放的释放形式且包括控制释放、持续释放和延缓释放。
本文所用的术语“延缓时间”指的是给予组合物与活性组分从特定成分中释放之间的期限。
本文所用的术语“延滞时间”指的是活性组分从一种成分中释放与活性组分从另一种成分中随后释放之间的时间。
根据将哌醋甲酯作为特别适合于本发明多颗粒改进释放组合物制剂的特殊实例来具体描述本发明。
本发明的多颗粒改进释放组合物可以具有含两种以上活性组分的成分。在这种情况中，活性组分从第二种和后续成分中的释放得到改进，使得活性组分从第一种成分中释放与从各后续成分中释放之间存在延滞时间。由这类组合物在起作用过程中产生的分布中的脉冲数量取决于组合物中含活性组分的成分的数量。包括含三种活性组分的成分的组合物产生三种脉冲分布。
可以将用于将搏动血浆分布的优点与减少剂量频率的方案结合起来的任意活性组分用于实施本发明。在实施本发明中特别有用的包括得益于在血浆浓度峰之间具有消除期的药理作用和/或治疗作用的活性组分，诸如那些对患者产生耐药性敏感的活性组分。活性组分的实例包括但不限于：肽类或蛋白质；激素类；止痛药；抗偏头痛药；抗凝血药；麻醉药拮抗剂；螯合剂；抗心绞痛药；化疗剂；镇静药；抗肿瘤药；前列腺素和抗利尿药；对中枢神经系统起作用的药物化合物诸如大脑刺激剂、例如哌醋甲酯；控制疼痛的活性组分；生物碱诸如阿片剂、例如吗啡；心血管药诸如硝酸酯；和用于治疗风湿性疾病的药物。进一步可以理解可以将本发明用于转运许多药物包括但不限于：肽类、蛋白质或激素诸如胰岛素；降钙素；降钙素基因调节蛋白；心房蛋白；集落刺激因子；重组干扰素β-1b；红细胞生成素(EPO)；诸如α、β或γ干扰素这样的干扰素；索马托品；促生长素；生长抑素(somastostatin)；胰岛素样生长因子(生长调节素)；黄体素释放激素(LHRH)；组织纤溶酶原激活物(TPA)；生长激素释放激素(GHRH)；催产素；雌二醇；生长激素；醋酸亮丙瑞林；因子VIII；诸如白细胞介素-2及其类似物这样的白细胞介素；诸如芬太尼、舒芬太尼、环丁羟吗喃、丁丙诺非、左啡诺、吗啡、二氢吗啡酮、二氢可待因酮、羟氢吗啡酮、美沙酮、利多卡因、布比卡因、双氯酚酸钠、萘普生、罂粟碱(paverin)及其类似物这样的止痛药；诸如舒马曲坦、麦角类生物碱及其类似物这样的抗偏头痛药；诸如肝素、水蛭素及其类似物这样的抗凝血药；诸如东莨菪碱、奥丹西隆、多潘立酮、甲氧氯普胺及其类似物这样的止吐药；诸如地尔硫
可乐定、硝苯地平、维拉帕米、莫诺确特、有机硝酸酯类、用于治疗心脏病的药物及其类似物这样的心血管药物、抗高血压药和血管舒张剂；诸如苯并二氮
类、吩噻嗪及其类似物这样的镇静药；诸如去铁敏及其类似物这样的螯合剂；诸如去氨加压素、加压素及其类似物这样的抗利尿药；诸如缓释硝酸甘油及其类似物这样的抗心绞痛药；诸如氟尿嘧啶、博来霉素及其类似物这样的抗肿瘤药；前列腺素及其类似物；以及诸如长春新碱及其类似物这样的化疗剂。
各成分中的活性组分可以相同或不同。例如，理想的是将含有第一部分活性组分的第一种成分和含有第二部分活性组分的第二种成分的组合物用于联合疗法。实际上，当活性组分彼此相容时，可以将两种或多种活性组分混入相同成分。例如，为了改进药物化合物的生物利用度或治疗作用，在组合物一种成分中存在的药物化合物中可以混有该组合物中另一种成分内的促进剂化合物或敏感剂化合物。
本文所用的术语“促进剂”指的是能够通过促进经动物、诸如人体内GIT的净转运而促进活性组分吸收和/或生物利用度的化合物。促进剂包括但不限于：中链脂肪酸类、盐、酯类、醚类及其衍生物(包括甘油酯类和甘油三酯类)；诸如那些可以通过使环氧乙烷与脂肪酸、脂肪醇、烷基酚或脱水山梨醇或脂肪酸甘油酯反应而制备的非离子型表面活性剂；细胞色素P450抑制剂；P-糖蛋白抑制剂等；以及这些试剂的两种或多种的混合物。
在各成分中所包含的活性组分的比例可以根据所需的给药方案而相同或不同。活性组分可以以足以引起治疗反应的任意量独立地存在于第一种成分中或存在于与第二种成分中的活性组分(或多种活性组分)混合。当施用时，活性组分(或多种活性组分)可以以一种基本上是光学纯的对映体的形式或作为对映体的混合物、外消旋物或其它形式存在。所述活性组分在组合物中的含有量优选为0.1-500mg、优选量为1-100mg。当活性组分是哌醋甲酯时，优选它在第一种成分中的含有量为0.5-60mg、更优选活性组分在第一种成分中的含有量为2.5-30mg。该活性组分在后续成分中的含有量与第一种成分中的含有量的范围类似。
从各成分中释放活性组分的释放时间特征可以通过改变各成分的组成、包括改变可以含有的任意赋形剂或包衣材料来改变。特别地，活性组分的释放可以通过改变颗粒上改进释放包衣层的组成和/或用量(如果这类包衣层存在)而得到控制。如果存在一种以上的改进释放成分，那么用于这些成分中每一种的改进释放包衣层可以相同或不同。类似地，当改进释放通过包含改进释放基质物质得到促进时，活性组分的释放可以通过所用改进释放基质物质的选择和用量得到控制。在各成分中，改进释放包衣层可以以足以产生各特定成分所需的延缓时间的任意量存在。在各成分中，改进释放包衣层可以以足以在成分之间产生所需的延滞时间的任意量存在。
从各成分中释放活性组分的延滞时间或延缓时间还可以通过改变各成分中的组成、包括改变可以含有的任意赋形剂和包衣材料来改变。例如，第一种成分可以是即时释放成分，其中活性组分基本上在给药时即刻释放。另一方面，例如，第一种成分可以是定时直接释放成分，其中活性组分基本上在延迟时间后立即释放。例如，第二种成分可以是如上所述的定时直接释放成分，或另一方面，它是定时持续释放或延长释放成分，其中活性组分在延长时间期限内以受控形式释放。
正如本领域技术人员可以理解的，血浆浓度曲线的确切性质会受到上述所有这些因素的综合影响。特别地，释放各成分中活性组分(且由此也开始起作用)之间的延滞时间可以通过改变各成分的组成和包衣层(如果存在)而得到控制。因此，通过改变各成分的组成(包括活性组分的用量和性质)并通过改变延滞时间可以获得大量释放和血浆分布。根据活性组分从各成分中释放之间延滞时间的期限和从各成分中释放的性质的不同(即即刻释放、持续释放等)，血浆分布中的脉冲峰可以得到充分分离且明确定义的峰(例如当延滞时间较长时)或脉冲峰可以叠加至一定程度(例如当延滞时间较短时)
在一个优选的实施方案中，本发明的多颗粒改进释放组合物具有即时释放成分和至少一种改进释放成分，所述的即时释放成分包括第一种含活性组分的第一部分颗粒群，而改进释放成分包括第二种含活性组分的后续颗粒群。第二种和后续改进释放成分可以包括一种控释包衣层。另外或另一方面，第二种和后续改进释放成分可以包括一种改进释放基质物质。在起作用过程中，例如，给予这类带有单一改进释放成分的多颗粒改进释放组合物产生特征性活性组分的搏动血浆浓度水平，其中该组合物中的即时释放成分产生血浆分布中的第一种峰，而改进释放成分产生血浆分布中的第二种峰。包括一种以上改进释放成分的本发明实施方案产生血浆分布中的另外的峰。
如果需要释放两种(或多种)脉冲的活性组分而不需给予两种(或多种)剂量单位，那么从给予单一剂量单位产生的这类血浆分布是有利的。另外，就某些疾病而言，特别有用的是具有这类双峰血浆分布。例如，典型的哌醋甲酯治疗方案由分别给予两种剂量的即时释放剂型4小时的步骤组成。已经发现这种类型的方案具有治疗有效性并广泛应用。由这类给药方案产生的血浆分布通过附图1中的“对照”曲线来解释。如上所述，患者耐药性的产生有时是与哌醋甲酯治疗方案相关的不良反应。认为两个峰值血浆浓度之间的血浆分布的最低值通过形成活性组分的消除期而有利于减少患者耐药性的产生。产生活性组分的零级或假零级转运的药物转运系统不会促进这种消除过程。
可以使用以所需形式改进活性组分释放的任意包衣材料。特别地，适用于实施本发明的包衣材料包括但不限于：聚合物包衣材料诸如乙酸邻苯二甲酸纤维素、乙酸三马来酸(trimaletate)纤维素、邻苯二甲酸羟丙基甲基纤维素、聚乙酸邻苯二甲酸乙烯酯、诸如那些在Eudragit
RS和RL商标下销售的甲基丙烯酸铵共聚物、诸如那些在EudragitS和L商标下销售的聚丙烯酸和聚丙烯酸酯与甲基丙烯酸酯共聚物、聚乙酸乙烯缩乙醛二乙氨酯、乙酸琥珀酸羟丙基甲基纤维素、紫胶片；水凝胶和胶凝物质诸如羧乙烯基聚合物、藻酸钠、羧甲基纤维素钠(sodium carmellose)、羧甲基纤维素钙(calciumcarmellose)、羧甲基淀粉钠、聚乙烯醇、羟乙基纤维素、甲基纤维素、明胶、淀粉和以纤维素为基础的交联聚合物-其中交联度较短以便促进水的吸收和聚合物基质的膨胀、羟丙基纤维素、羟丙基甲基纤维素、聚乙烯吡咯烷酮、交联淀粉、微晶纤维素、壳多糖、甲基丙烯酸氨基丙烯酰胺酯共聚物(EudragitRS-PM，Rohm & Haas)、普鲁兰、胶原蛋白、酪蛋白、琼脂、阿拉伯胶、羧甲基纤维素钠、(可膨胀亲水性聚合物)聚(甲基丙烯酸羟烷基酯)(m.wt.～5k-5,000k)、聚乙烯吡咯烷酮(m.wt.～10k-360k)、阴离子和阳离子型水凝胶、带有低级乙酸酯残基的聚乙烯醇、琼脂与羧甲基纤维素的可膨胀混合物、马来酐与苯乙烯、乙烯、丙烯或异丁烯的共聚物；果胶(m.wt.～30k-300k)；诸如琼脂、阿拉伯胶、梧桐胶、西黄蓍胶、藻酸铵和瓜耳胶这样的多糖类；聚丙烯酰胺类；Polyox
聚环氧乙烷类(m.wt.～100k-5,000k)；AquaKeep丙烯酸酯聚合物；聚葡聚糖的二酯类；AquaKeep
丙烯酸酯聚合物、聚葡聚糖二酯类、交联聚乙烯醇和聚N-乙烯基-2-吡咯烷酮、羟基乙酸淀粉钠(sodium starch glucolate)(例如Explotab
；Edward Mandell C.Ltd.)；亲水性聚合物诸如多糖类、甲基纤维素、羧甲基纤维素钠或钙、羟丙基甲基纤维素、羟丙基纤维素、羟乙基纤维素、硝基纤维素、羧甲基纤维素、纤维素醚类、聚环氧乙烷类(例如Polyox
，Union Carbide)、甲基乙基纤维素、乙基羟乙基纤维素、乙酸纤维素、丁酸纤维素、丙酸纤维素、明胶、胶原蛋白、淀粉、麦芽糖糊精、普鲁兰、聚乙烯吡咯烷酮、聚乙烯醇、聚乙酸乙烯酯、脂肪酸甘油酯类、聚丙烯酰胺、聚丙烯酸、甲基丙烯酸共聚物或甲基丙烯酸(例如Eudragit
，Rohm & Haas)、其它丙烯酸衍生物、脱山梨醇酯类、天然树胶、卵磷脂、果胶、藻酸盐、藻酸铵、藻酸钠、藻酸钙、藻酸钾、藻酸丙二醇酯、琼脂和诸如阿拉伯胶、梧桐胶、刺槐豆胶、西黄蓍胶、瓜耳胶、黄原胶、小菌核聚糖(scleroglucan)及其混合物和掺合物。正如本领域技术人员可以理解的，可以向包衣层中添加诸如增塑剂、润滑剂、溶剂等这样的赋形剂。合适的增塑剂包括：例如乙酰化单酸甘油酯类；甘醇酸丁基邻苯二甲酰基丁酯；酒石酸二丁酯；邻苯二甲酸二乙酯；邻苯二甲酸二甲酯；甘醇酸丁基邻苯二甲酰基乙酯；甘油；丙二醇；三醋精；柠檬酸酯；三丙酸甘油酯(tripropioin)；二醋精；邻苯二甲酸二丁酯；乙酰基单酸甘油酯类；聚乙二醇类；蓖麻油；柠檬酸三乙酯；多元醇类；甘油；乙酸酯类；三乙酸甘油酯类；柠檬酸乙酰基三乙酯；邻苯二甲酸二苄酯；邻苯二甲酸二己酯；邻苯二甲酸丁基辛酯；邻苯二甲酸二异壬酯；邻苯二甲酸丁基辛酯；壬二酸二辛酯；环氧化树脂酸酯；偏苯三酸三异辛酯；邻苯二甲酸二乙基己酯；邻苯二甲酸二正辛酯；邻苯二甲酸二异辛酯；邻苯二甲酸二异癸酯；邻苯二甲酸二正十一酯；邻苯二甲酸二正十三酯；偏苯三酸三-2-乙基己酯；己二酸二-2-乙基己酯；癸二酸二-2-乙基己酯；壬二酸二-2-乙基己酯；癸二酸二丁酯。
在本发明一个方面，甲基丙烯酸酯与甲基丙烯酸铵共聚物的比例为1∶1。
当改进释放成分包括改进释放的基质物质时，可以使用任意合适的改进释放基质物质或合适的改进释放基质物质的混合物。这类物质对本领域技术人员来说是公知的。本文所用的术语“改进释放的基质物质”包括能够在体外或体内改进分散在其中的活性组分的释放的亲水性聚合物、疏水性聚合物及其混合物。适合于实施本发明的改进释放的基质物质包括但不限于：微晶纤维素；羧甲基纤维素钠；诸如羟丙基甲基纤维素和羟丙基纤维素这样的羟烷基纤维素；聚环氧乙烷；聚乙烯吡咯烷酮；乙酸纤维素；乙酸丁酸纤维素；乙酸邻苯二甲酸纤维素；乙酸偏苯三酸纤维素；聚乙酸邻苯二甲酸乙烯酯；聚烷基甲基丙烯酸酯；聚乙酸乙烯酯及其混合物。
可以将本发明的多颗粒改进释放组合物制成有利于以搏动方式释放活性组分的任意合适的剂型。一般来说，该剂型可以是构成即时释放和改进释放成分的含活性组分的不同颗粒群的掺合物，将该掺合物填入诸如硬胶囊或软胶囊这样的合适的胶囊中。另一方面，可以将含活性组分的各不同颗粒群压制(可以与另外的赋形剂一起或不与赋形剂一起)成随后可以适当比例填入胶囊的微片。另一种合适的剂型是多层片剂型。在这种情况中，可以将多颗粒改进释放组合物的第一种成分压制成一层，随后将第二种成分作为该多层片的第二层加入。构成本发明组合物的含活性组分的颗粒群可以进一步涉及快速溶解诸如泡腾剂型或速熔剂型这样的剂型。
本发明的组合物包括至少在体外具有不同溶解分布的两种含活性组分的颗粒群。
在起作用过程中，优选本发明的组合物和含有该组合物的固体口服剂型释放活性组分，使得在从第二种成分中释放活性组分前释放第一种成分中包含的基本上全部的活性组分。例如，当第一种成分包括IR成分时，优选使从第二种成分中释放活性组分的过程延缓至基本上IR成分中所有活性组分已经释放完成为止。可以如上所述通过使用改进释放包衣层和/或改进释放基质物质来延缓活性组分从第二种成分中的释放。
当需要通过提供有利于从患者系统中消除第一种剂量的活性组分的剂量方案而将患者的耐药性降低到最低限度时，更优选使从第二种成分中释放活性组分的过程延缓至基本上第一种成分中包含的所有活性组分已经释放完成为止且进一步延缓至从第一种成分中释放的最后一部分活性组分已经从患者系统中清除为止。在一个优选的实施方案中，在起作用过程中活性组分从所述组合物第二种成分中的释放基本上完全；如果不完全，那么可以在给予该组合物后将这一过程至少延缓约2小时。
当活性组分是哌醋甲酯时，在起作用过程中活性组分从所述组合物第二种成分中的释放基本上完全；如果不完全，那么可以在给予该组合物后将这一过程至少延缓约4小时、优选约4小时。
在下列实施例中，除非另有说明，所有百分比均为重量百分比。实施例中所用的术语“纯水”指的是通过水过滤系统而纯化的水。
实施例1.含有哌醋甲酯的多颗粒改进释放组合物
如下制备本发明的多颗粒改进释放组合物，它包括即时释放成分和改进释放成分并含有作为活性组分的哌醋甲酯。
(a)即时释放成分
按照表1中给出的任意配方制备盐酸哌醋甲酯(50∶50外消旋混合物)溶液。然后，例如使用Glatt GPCG3(Glatt，Protech Ltd.，Leicester，UK)流化床包衣设备将哌醋甲酯溶液包衣至六点间隔晶种且所得固体重量浓度约16.9％以便形成即时释放成分的IR颗粒
(b)改进释放成分
通过用表2中所述改进释放包衣溶液给上述实施例1(a)中制备的即时释放颗粒包衣来制备含有哌醋甲酯的缓释颗粒。例如，使用一种流化床设备将即时释放颗粒包衣至重量增加约达30％的可变水平。
1在(i)、(iv)和(vi)栏中制剂的包衣过程中同时施用滑石。
(c)溶解测试
使用USP 1型设备(100rpm)按照下列方案在体外测试pH依赖性包衣成分(表2(i)-(v))：在所有的取样时间点，在37℃下将样品置于pH为2.0的0.01N HCl(900ml)中。
使用USP 1型设备(100rpm)按照美国药典修改版的肠溶保护法(USP 23，1995，1795页)在体外测试pH依赖性包衣成分(表2(vi)-(viii))：在所有剩余的取样时间点时，将样品置于0.01N HCl中2小时且然后转入pH 6.8的磷酸盐缓冲液中。
使用分别具有0.5-0.6、0.6-0.71和0.71-0.85mm直径大小的三种不同大小的独特颗粒配制IR成分。发现通过给0.5-0.6、0.6-0.71和0.71-0.85mm独特颗粒包衣而形成的IR颗粒可在水介质中在20分钟内释放100％的活性组分。
按照上述实施例1(b)制备的改进释放成分的溶解数据如表3(a)-3(c)中所示。该数据表明通过改变所用包衣层的组成和厚度可以改变改进释放成分的释放特性。
(符号“-”表示未给出测定值)
(符号“-”表示未给出测定值)
(符号“-”表示未给出测定值；“*”表示磷酸盐缓冲液的pH为7.4而不是6.8)
(d)即时和延缓释放颗粒的包囊
例如，使用Bosch GKF 4000S包囊设备将按照上述实施例1(a)和(b)制备的即时和延缓释放颗粒包入2号硬胶囊至总计20mg剂量浓度。20mg哌醋甲酯的总剂量浓度由10mg即时释放成分和10mg改进释放成分组成。
表4表明了使用表1(ii)给出的即时释放包衣溶液和表2(vii)和(viii)给出的改进释放包衣溶液制备的两种多颗粒改进释放组合物的溶解分布。这些结果表明约50％的活性组分盐酸哌醋甲酯在前半小时内释放，而改进释放成分延缓约4小时释放。
表4中所示的溶解分布表明含有pH依赖性包衣成分的组合物以一种脉冲方式释放活性组分哌醋甲酯。第一次脉冲发生在1小时前，随后是其它量活性组分释放受到抑制的坪值区(plateauregion)。坪值区后依次是4小时以上药物浓度增加所表示的活性组分释放的第二次脉冲。
实施例2.含有哌醋甲酯的多颗粒改进释放组合物
按照表5(a)和(b)中所示配方制备具有即时释放成分和改进释放成分并具有改进释放基质物质的本发明多颗粒哌醋甲酯改进释放组合物。
(e)体内释放
在人体交叉生物研究中，对禁食的健康志愿者给予20mg的本发明盐酸哌醋甲酯组合物以比较这些组合物中盐酸哌醋甲酯与Ritalin
(Novartis；以4小时间隔给予2次10mg剂量)中盐酸哌醋甲酯的生物利用度。药代动力学评价以给药后以定期间隔达48小时取血样测定的哌醋甲酯血浆浓度为基础。另外取血样进行研究前和研究后的筛选。
现在参照附图1，标称“A”(改进成分包括用表2(viii)包衣材料以30％包衣的IR颗粒)和“B”(改进成分包括用表2(vii)包衣材料以30％包衣的IR颗粒)的血浆分布符合给予按照实施例1制备的多颗粒改进释放组合物后在人体志愿者中观察到的哌醋甲酯的血浆浓度。在两种情况中，血浆分布定性地与以现有技术治疗方法为特征的对照组(附图1中标称的“对照”)相类似，所述现有技术的治疗方法由分别依次给予两次剂量的Ritalin
IR 4小时的步骤组成。
对于按照上述实施例1制备的分本发明多颗粒改进释放组合物来说，在血浆分布中与即时释放成分相关的用Cmax表示的第一个峰和峰宽与涉及对照分布中第一次剂量Ritalin的峰相类似。分布A表示按照本发明制备的组合物可模拟(mimicked)通常每日两次给药的最低特征(以对照分布为特征)。B还显示出在初始血浆浓度峰后的显著下降。对于两种多颗粒改进释放组合物来说，改进释放成分的作用在于增加给药后的血浆浓度4小时，从而产生第二个峰值浓度。这种观察到的作用再次与对照组类似。
从附图1中清楚地观察到：按照本发明制备的多颗粒改进释放组合物可模拟以给药时达到的血浆分布为代表的典型的每日两次给药疗法(由对照组代表)。与每日两次给予Ritalin相比，可以在体内实现从本发明组合物中释放哌醋甲酯而没有任何生物利用度的损失。
在一种单独的研究中，对34名儿童给予本发明20mg的盐酸哌醋甲酯组合物。将模拟教室设计用于将制剂“A”和“B”(相当于上述“A”和“B”配方)与安慰剂比较。在测定按照SKAMP等级确定的注意力和行为以及通过所尝试的数学难题的数量和正确答案的数量测定测定能力结果的9小时时间期限内进行药效学评价。各制剂与安慰剂相比在所有功效测定结果方面均有统计学差异。各功效评价结果表明“A”和“B”制剂在有关注意力方面均显示出类似性。根据注意力和能力结果显示，看起来使用“A”制剂的儿童比服用“B”制剂的儿童在动手方面注意力更为集中且试图在4-6小时内尽可能更快地解决更多的数学难题。
本发明并不限于本文所述的特定实施方案的范围。本领域技术人员显然可以根据上述描述和下面的权利要求对包括本文所述的那些技术方案在内的本发明作各种修改。
Claims (19)
1.多颗粒改进释放组合物，包括：
a)含有活性成分的即时释放颗粒，和；
b)含有即时释放颗粒的改进释放颗粒，用包含甲基丙烯酸铵共聚物、甲基丙烯酸共聚物、增塑剂和溶剂的包衣溶液包衣；
其中所述活性成分是哌醋甲酯、哌醋甲酯的可药用盐、哌醋甲酯的对映异构体或其混合物，其中的多颗粒改进释放组合物在经口服递送给患者后，以脉冲方式递送活性成分，其特征在于高活性成分浓度的脉冲之间散布有低活性成分浓度的时期。
2.权利要求1的多颗粒改进释放组合物，其中所述增塑剂是柠檬酸三乙酯。
3.权利要求1多颗粒改进释放组合物，其中所述溶剂是异丙醇。
4.权利要求1的多颗粒改进释放组合物，其中包含在所述包衣溶液中的所述甲基丙烯酸共聚物的量是含量为25.0％w/w的L 12.5。
5.权利要求1的多颗粒改进释放组合物，其中甲基丙烯酸共聚物与甲基丙烯酸铵共聚物的比例为1∶1w/w，并且其中所述甲基丙烯酸共聚物和甲基丙烯酸铵共聚物分别是
L 12.5和
RS 12.5。
6.权利要求1的多颗粒改进释放组合物，其中所述包衣溶液还包括聚乙烯吡咯烷酮。
7.权利要求1的多颗粒改进释放组合物，包括所述包衣溶液还包括邻苯二甲酸二乙酯。
8.权利要求7的多颗粒改进释放组合物，其中所述包衣溶液中的邻苯二甲酸二乙酯的量为1.1％w/w。
9.权利要求1的多颗粒改进释放组合物，其中所述包衣溶液中的增塑剂的量为1.25％w/w。
10.权利要求1的多颗粒改进释放组合物，其中所述包衣溶液中的溶剂的量为46.5％w/w。
11.权利要求1的多颗粒改进释放组合物，其中所述包衣溶液还包括丙酮。
12.权利要求1的多颗粒改进释放组合物，其中所述包衣溶液中还包括滑石。
13.权利要求12的多颗粒改进释放组合物，其中所述包衣溶液中的滑石的量为2.25％w/w。
14.权利要求1的多颗粒改进释放组合物，其中所述改进释放颗粒含有25.0％w/w的甲基丙烯酸铵共聚物、25.0％w/w的甲基丙烯酸共聚物、1.25％w/w的柠檬酸三乙酯、46.5％w/w的异丙醇和2.25％w/w的滑石，其中所述甲基丙烯酸铵共聚物和甲基丙烯酸共聚物分别是
RS 12.5和
L 12.5。
15.权利要求1的多颗粒改进释放组合物，其中所述增塑剂是柠檬酸三乙酯，溶剂是异丙醇。
16.权利要求1的多颗粒改进释放组合物，其中应用到即时释放颗粒上的包衣使颗粒的重量增加20％。
17.权利要求1的多颗粒改进释放组合物，其中哌醋甲酯包括一种光学纯对映异构体或对映异构体的混合物。
18.权利要求1的多颗粒改进释放组合物，其中即时释放颗粒与改进释放颗粒之比为1∶1w/w。
19.权利要求1的多颗粒改进释放组合物在制备治疗注意力不集中疾病的药物中的用途。
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Families Citing this family (376)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6486177B2 (en) * | 1995-12-04 | 2002-11-26 | Celgene Corporation | Methods for treatment of cognitive and menopausal disorders with D-threo methylphenidate |
| US5837284A (en) * | 1995-12-04 | 1998-11-17 | Mehta; Atul M. | Delivery of multiple doses of medications |
| US5922736A (en) * | 1995-12-04 | 1999-07-13 | Celegene Corporation | Chronic, bolus administration of D-threo methylphenidate |
| US8071128B2 (en) | 1996-06-14 | 2011-12-06 | Kyowa Hakko Kirin Co., Ltd. | Intrabuccally rapidly disintegrating tablet and a production method of the tablets |
| US8022095B2 (en) * | 1996-08-16 | 2011-09-20 | Pozen, Inc. | Methods of treating headaches using 5-HT agonists in combination with long-acting NSAIDs |
| US6962997B1 (en) * | 1997-05-22 | 2005-11-08 | Celgene Corporation | Process and intermediates for resolving piperidyl acetamide steroisomers |
| US6322819B1 (en) * | 1998-10-21 | 2001-11-27 | Shire Laboratories, Inc. | Oral pulsed dose drug delivery system |
| AU2004200325B2 (en) * | 1998-10-21 | 2006-09-28 | Shire Llc | Oral Pulsed Dose Drug Delivery System |
| CN100444830C (zh) * | 1998-11-02 | 2008-12-24 | 伊兰公司，Plc | 多颗粒改进释放组合物 |
| US20090149479A1 (en) * | 1998-11-02 | 2009-06-11 | Elan Pharma International Limited | Dosing regimen |
| US20060240105A1 (en) * | 1998-11-02 | 2006-10-26 | Elan Corporation, Plc | Multiparticulate modified release composition |
| US20080113025A1 (en) * | 1998-11-02 | 2008-05-15 | Elan Pharma International Limited | Compositions comprising nanoparticulate naproxen and controlled release hydrocodone |
| US20080102121A1 (en) * | 1998-11-02 | 2008-05-01 | Elan Pharma International Limited | Compositions comprising nanoparticulate meloxicam and controlled release hydrocodone |
| US20090297602A1 (en) * | 1998-11-02 | 2009-12-03 | Devane John G | Modified Release Loxoprofen Compositions |
| US20070122481A1 (en) * | 1998-11-02 | 2007-05-31 | Elan Corporation Plc | Modified Release Compositions Comprising a Fluorocytidine Derivative for the Treatment of Cancer |
| US6419960B1 (en) * | 1998-12-17 | 2002-07-16 | Euro-Celtique S.A. | Controlled release formulations having rapid onset and rapid decline of effective plasma drug concentrations |
| US7083808B2 (en) | 1998-12-17 | 2006-08-01 | Euro-Celtique S.A. | Controlled/modified release oral methylphenidate formulations |
| US6673367B1 (en) | 1998-12-17 | 2004-01-06 | Euro-Celtique, S.A. | Controlled/modified release oral methylphenidate formulations |
| US6723342B1 (en) | 1999-02-08 | 2004-04-20 | Fmc Corporation | Edible coating composition |
| US6432448B1 (en) | 1999-02-08 | 2002-08-13 | Fmc Corporation | Edible coating composition |
| EP1163001A2 (en) * | 1999-03-24 | 2001-12-19 | The Secretary of State for Defence | Vaccine composition |
| US20030170181A1 (en) * | 1999-04-06 | 2003-09-11 | Midha Kamal K. | Method for preventing abuse of methylphenidate |
| US6500462B1 (en) * | 1999-10-29 | 2002-12-31 | Fmc Corporation | Edible MCC/PGA coating composition |
| US10179130B2 (en) | 1999-10-29 | 2019-01-15 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
| RU2230556C2 (ru) | 1999-10-29 | 2004-06-20 | Эро-Селтик, С.А. | Препаративные формы гидрокодона с контролируемым высвобождением |
| EP1248594B1 (en) | 2000-01-19 | 2005-12-14 | Mannkind Corporation | Multi-spike release formulation for drug delivery |
| US6565882B2 (en) | 2000-02-24 | 2003-05-20 | Advancis Pharmaceutical Corp | Antibiotic composition with inhibitor |
| US6544555B2 (en) | 2000-02-24 | 2003-04-08 | Advancis Pharmaceutical Corp. | Antibiotic product, use and formulation thereof |
| AU780182B2 (en) * | 2000-03-22 | 2005-03-03 | Secretary Of State For Defence, The | Pharmaceutical composition for administration to mucosal surfaces |
| WO2001087284A2 (en) * | 2000-05-11 | 2001-11-22 | Pharmacia Corporation | Aldosterone antagonist composition for release during aldosterone acrophase |
| US6500457B1 (en) * | 2000-08-14 | 2002-12-31 | Peirce Management, Llc | Oral pharmaceutical dosage forms for pulsatile delivery of an antiarrhythmic agent |
| CA2420535A1 (en) * | 2000-08-30 | 2002-03-07 | Mary Tanya Am Ende | Sustained release formulations for growth hormone secretagogues |
| US6541014B2 (en) | 2000-10-13 | 2003-04-01 | Advancis Pharmaceutical Corp. | Antiviral product, use and formulation thereof |
| US20020068078A1 (en) | 2000-10-13 | 2002-06-06 | Rudnic Edward M. | Antifungal product, use and formulation thereof |
| US6344215B1 (en) * | 2000-10-27 | 2002-02-05 | Eurand America, Inc. | Methylphenidate modified release formulations |
| HU230875B1 (hu) | 2000-10-30 | 2018-11-29 | Euro-Celtique S.A. | Szabályozott hatóanyag-leadású hidrokodon készítmények |
| IT1319655B1 (it) | 2000-11-15 | 2003-10-23 | Eurand Int | Microsfere di enzimi pancreatici con elevata stabilita' e relativometodo di preparazione. |
| AU2002225763A1 (en) * | 2000-11-28 | 2002-06-11 | Fmc Corporation | Edible pga(propylene glycol alginate) coating composition |
| US6932861B2 (en) | 2000-11-28 | 2005-08-23 | Fmc Corporation | Edible PGA coating composition |
| JP4170762B2 (ja) * | 2001-02-09 | 2008-10-22 | 冷化工業株式会社 | 機能性粒子及びその製造方法及びプラズマ処理方法 |
| IL157634A0 (en) * | 2001-03-13 | 2004-03-28 | Penwest Pharmaceuticals Co | Chronotherapeutic dosage forms containing glucocorticosteroid |
| CA2447008A1 (en) * | 2001-04-05 | 2002-10-24 | Collagenex Pharmaceuticals, Inc. | Controlled delivery of tetracycline compounds and tetracycline derivatives |
| US8329216B2 (en) * | 2001-07-06 | 2012-12-11 | Endo Pharmaceuticals Inc. | Oxymorphone controlled release formulations |
| DE60219478T2 (de) * | 2001-07-06 | 2008-01-03 | Endo Pharmaceuticals Inc. | Orale gabe von 6-hydroxy-oxymorphon als analgetikum |
| US20070254009A1 (en) * | 2001-07-13 | 2007-11-01 | Flow Focusing, Inc. | Antibiotic/bone morphogenic protein formulation and method of treatment |
| US20070254008A1 (en) * | 2001-07-13 | 2007-11-01 | Flow Focusing, Inc. | Antibiotic formulation and method of treatment |
| US20040142013A1 (en) * | 2001-07-13 | 2004-07-22 | Flow Focusing, Inc. | Implantable orthopedic surgical devices with controlled release antimicrobial component |
| US20060263401A1 (en) * | 2001-07-13 | 2006-11-23 | Flow Focusing, Inc. | Formulation and Method for Preventing Infection |
| US20030055075A1 (en) * | 2001-07-13 | 2003-03-20 | Rubsamen Reid M. | Programmable controlled release injectable opioid formulation |
| WO2003005996A1 (en) * | 2001-07-13 | 2003-01-23 | Flow Focusing, Inc. | Programmable controlled release injectable opioid formulation |
| US20030044458A1 (en) * | 2001-08-06 | 2003-03-06 | Curtis Wright | Oral dosage form comprising a therapeutic agent and an adverse-effect agent |
| AU2002324624A1 (en) | 2001-08-06 | 2003-02-24 | Euro-Celtique S.A. | Sequestered antagonist formulations |
| PL367427A1 (en) | 2001-08-06 | 2005-02-21 | Euro-Celtique S.A. | Opioid agonist formulations with releasable and sequestered antagonist |
| US20150031718A1 (en) * | 2001-08-06 | 2015-01-29 | Purdue Pharma L.P. | Pharmaceutical Formulation Containing Opioid Agonist, Opioid Antagonist and Gelling Agent |
| US20030068375A1 (en) | 2001-08-06 | 2003-04-10 | Curtis Wright | Pharmaceutical formulation containing gelling agent |
| EP1429730A4 (en) * | 2001-09-26 | 2010-06-16 | Penwest Pharmaceuticals Compan | OPIOID FORMULATIONS WITH REDUCED ABUSE POTENTIAL |
| US9358214B2 (en) | 2001-10-04 | 2016-06-07 | Adare Pharmaceuticals, Inc. | Timed, sustained release systems for propranolol |
| FR2830447B1 (fr) * | 2001-10-09 | 2004-04-16 | Flamel Tech Sa | Forme galenique orale microparticulaire pour la liberation retardee et controlee de principes actifs pharmaceutiques |
| US8101209B2 (en) * | 2001-10-09 | 2012-01-24 | Flamel Technologies | Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active principles |
| AUPR839001A0 (en) * | 2001-10-19 | 2001-11-15 | Eli Lilly And Company | Dosage form, device and methods of treatment |
| EP2305252A1 (en) * | 2001-12-11 | 2011-04-06 | University Of Virginia Patent Foundation | Use of pramipexole to treat amyotrophic lateral sclerosis |
| US20060281797A1 (en) * | 2001-12-11 | 2006-12-14 | University Of Virginia Patent Foundation | Neurorestoration with R(+) Pramipexole |
| US6663888B2 (en) * | 2001-12-14 | 2003-12-16 | Eurand Pharmaceuticals Ltd. | Pulsatile release histamine H2 antagonist dosage form |
| US20050025824A1 (en) * | 2001-12-14 | 2005-02-03 | Eurand Pharmaceuticals Ltd. | Pulsatile release histamine H2 antagonist dosage form |
| EP1490031A1 (en) * | 2002-03-07 | 2004-12-29 | Vectura Limited | Fast melt multiparticulate formulations for oral delivery |
| JP4732696B2 (ja) | 2002-04-09 | 2011-07-27 | フラメル・テクノロジー | 活性成分の改変された放出のための、マイクロカプセルの水性懸濁液形態での経口医薬品製剤 |
| ES2314227T7 (es) * | 2002-04-09 | 2012-11-19 | Flamel Technologies | Formulacion farmaceutica oral en forma de suspension acuosa de microcapsulas que permiten la liberacion modificada de amoxilicina. |
| US7053034B2 (en) * | 2002-04-10 | 2006-05-30 | Salvona, Llc | Targeted controlled delivery compositions activated by changes in pH or salt concentration |
| CA2395819A1 (en) * | 2002-08-13 | 2004-02-13 | Bernard Charles Sherman | Dual-spike release formulation for oral drug delivery |
| US7445796B2 (en) * | 2002-08-19 | 2008-11-04 | L. Perrigo Company | Pharmaceutically active particles of a monomodal particle size distribution and method |
| WO2004034959A2 (en) * | 2002-09-18 | 2004-04-29 | Elan Corporation, Plc | Multiparticulate modified release composition comprising beraprost |
| US6913768B2 (en) * | 2002-09-24 | 2005-07-05 | Shire Laboratories, Inc. | Sustained release delivery of amphetamine salts |
| US20080220074A1 (en) * | 2002-10-04 | 2008-09-11 | Elan Corporation Plc | Gamma radiation sterilized nanoparticulate docetaxel compositions and methods of making same |
| MY148805A (en) * | 2002-10-16 | 2013-05-31 | Takeda Pharmaceutical | Controlled release preparation |
| US20050191244A1 (en) * | 2002-10-25 | 2005-09-01 | Gruenenthal Gmbh | Abuse-resistant pharmaceutical dosage form |
| CA2501324A1 (en) * | 2002-10-30 | 2004-05-21 | Pharmacia Corporation | Oral extended release tablets and methods of making and using the same |
| US20050038042A1 (en) * | 2002-11-15 | 2005-02-17 | Jenet Codd | Modified release composition comprising a short-acting hypnotic for treatment of sleep disorders |
| GB0228571D0 (en) | 2002-12-06 | 2003-01-15 | Novartis Ag | Organic compounds |
| US7988993B2 (en) | 2002-12-09 | 2011-08-02 | Andrx Pharmaceuticals, Inc. | Oral controlled release dosage form |
| CN101797221B (zh) | 2002-12-13 | 2013-06-12 | 杜雷科特公司 | 包含高粘度液体载体材料的口服递药系统 |
| CA2510465A1 (en) * | 2002-12-18 | 2004-07-08 | Pain Therapeutics | Oral dosage forms with therapeutically active agents in controlled release cores and immediate release gelatin capsule coats |
| WO2004060355A1 (en) * | 2002-12-26 | 2004-07-22 | Pozen Inc. | Multilayer Dosage Forms Containing NSAIDs and Triptans |
| US8367111B2 (en) | 2002-12-31 | 2013-02-05 | Aptalis Pharmatech, Inc. | Extended release dosage forms of propranolol hydrochloride |
| US7153526B2 (en) * | 2003-02-26 | 2006-12-26 | Frank Steven R | Treatment of gastrointestinal infections |
| US20050152967A1 (en) * | 2003-03-28 | 2005-07-14 | Pfab, Lp | Dynamic variable release |
| US20050137265A1 (en) * | 2003-03-31 | 2005-06-23 | Haley Eugene T. | Rapidly dissolving metoclopramide solid oral dosage and method thereof |
| US20040192781A1 (en) * | 2003-03-31 | 2004-09-30 | Haley Eugene T. | Method of administration for metoclopramide and pharmaceutical formulation therefor |
| CA2520321A1 (en) * | 2003-04-04 | 2004-10-14 | Pharmacia Corporation | Oral extended release compressed tablets of multiparticulates |
| ES2534827T3 (es) | 2003-04-07 | 2015-04-29 | Supernus Pharmaceuticals, Inc. | Formulaciones de tetraciclinas en dosis única diaria |
| US8158149B2 (en) * | 2004-05-12 | 2012-04-17 | Chelsea Therapeutics, Inc. | Threo-DOPS controlled release formulation |
| WO2004100929A1 (en) | 2003-05-12 | 2004-11-25 | Synergia Pharma, Inc. | Threo-dops controlled release formulation |
| CA2529984C (en) | 2003-06-26 | 2012-09-25 | Isa Odidi | Oral multi-functional pharmaceutical capsule preparations of proton pump inhibitors |
| WO2005009368A2 (en) | 2003-07-21 | 2005-02-03 | Advancis Pharmaceutical Corporation | Antibiotic product, use and formulation thereof |
| JP2006528185A (ja) | 2003-07-21 | 2006-12-14 | アドバンシス ファーマスーティカル コーポレイション | 抗生物質製剤、その使用法及び作成方法 |
| AU2004258949B2 (en) | 2003-07-21 | 2011-02-10 | Shionogi, Inc. | Antibiotic product, use and formulation thereof |
| WO2005016311A1 (en) | 2003-08-11 | 2005-02-24 | Advancis Pharmaceutical Corporation | Robust pellet |
| WO2005016278A2 (en) | 2003-08-12 | 2005-02-24 | Advancis Pharmaceuticals Corporation | Antibiotic product, use and formulation thereof |
| WO2005016317A1 (en) * | 2003-08-19 | 2005-02-24 | Themis Laboratories Private Limited | Process for manufacture of extended release pellets containing diltiazem hci |
| JP5686494B2 (ja) | 2003-08-29 | 2015-03-18 | シオノギ インコーポレイテッド | 抗生物質製剤、その使用法及び作成方法 |
| WO2005023217A2 (en) * | 2003-09-03 | 2005-03-17 | Mallinckrodt Inc. | Granular sustained release preparation and production thereof |
| AU2004273830B2 (en) | 2003-09-15 | 2011-03-24 | Shionogi, Inc. | Antibiotic product, use and formulation thereof |
| US7906125B2 (en) * | 2003-09-18 | 2011-03-15 | Boston Scientific Scimed, Inc. | Solid or semi-solid therapeutic formulations |
| AU2004273958A1 (en) | 2003-09-19 | 2005-03-31 | Penwest Pharmaceuticals Co. | Chronotherapeutic dosage forms |
| WO2005027878A1 (en) * | 2003-09-19 | 2005-03-31 | Penwest Pharmaceuticals Co. | Delayed released dosage forms |
| US8007827B2 (en) * | 2004-04-02 | 2011-08-30 | Impax Laboratories, Inc. | Pharmaceutical dosage forms having immediate release and/or controlled release properties |
| US20050226927A1 (en) * | 2004-04-02 | 2005-10-13 | Impax Laboratories, Inc. | Pharmaceutical dosage forms having immediate release and/or controlled release properties that contain a GABAB receptor agonist |
| US20050220873A1 (en) * | 2004-04-02 | 2005-10-06 | Chien-Hsuan Han | Pharmaceutical dosage forms having immediate and controlled release properties that contain a GABAB receptor agonist |
| US20050239830A1 (en) * | 2004-04-26 | 2005-10-27 | Vikram Khetani | Methods of diminishing co-abuse potential |
| WO2006009602A2 (en) | 2004-06-16 | 2006-01-26 | Tap Pharmaceutical Products, Inc. | Multiple ppi dosage form |
| US8394409B2 (en) * | 2004-07-01 | 2013-03-12 | Intellipharmaceutics Corp. | Controlled extended drug release technology |
| EP1771158A4 (en) | 2004-07-02 | 2008-03-12 | Advancis Pharmaceutical Corp | TABLET FOR PULSE DISTRIBUTION |
| CA2617941C (en) * | 2004-08-23 | 2012-07-24 | Pejo Iserlohn Heilmittel Und Diaet Gmbh & Co. Kg | Psychostimulant containing pharmaceutical composition |
| US10624858B2 (en) | 2004-08-23 | 2020-04-21 | Intellipharmaceutics Corp | Controlled release composition using transition coating, and method of preparing same |
| US9149472B2 (en) | 2004-08-31 | 2015-10-06 | Jack William Schultz | Controlled release compositions for treatment of cognitive, emotional and mental ailments and disorders |
| US8747895B2 (en) | 2004-09-13 | 2014-06-10 | Aptalis Pharmatech, Inc. | Orally disintegrating tablets of atomoxetine |
| GB0421121D0 (en) * | 2004-09-22 | 2004-10-27 | Natrocell Technologies Ltd | Composite rodenticide |
| US8312836B2 (en) | 2004-09-28 | 2012-11-20 | Atrium Medical Corporation | Method and apparatus for application of a fresh coating on a medical device |
| US9801982B2 (en) | 2004-09-28 | 2017-10-31 | Atrium Medical Corporation | Implantable barrier device |
| US9000040B2 (en) | 2004-09-28 | 2015-04-07 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
| US8367099B2 (en) | 2004-09-28 | 2013-02-05 | Atrium Medical Corporation | Perforated fatty acid films |
| WO2007011385A2 (en) | 2004-09-28 | 2007-01-25 | Atrium Medical Corporation | Heat cured gel and method of making |
| US8263102B2 (en) | 2004-09-28 | 2012-09-11 | Atrium Medical Corporation | Drug delivery coating for use with a stent |
| US8124127B2 (en) | 2005-10-15 | 2012-02-28 | Atrium Medical Corporation | Hydrophobic cross-linked gels for bioabsorbable drug carrier coatings |
| US9012506B2 (en) | 2004-09-28 | 2015-04-21 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
| US9884014B2 (en) | 2004-10-12 | 2018-02-06 | Adare Pharmaceuticals, Inc. | Taste-masked pharmaceutical compositions |
| US20060078621A1 (en) * | 2004-10-13 | 2006-04-13 | Wedinger Robert S | Method of providing customized drug delivery systems |
| ES2409347T3 (es) | 2004-10-21 | 2013-06-26 | Aptalis Pharmatech, Inc. | Composiciones farmacéuticas de sabor enmascarado con agentes porogénicos gastrosolubles |
| AR051654A1 (es) * | 2004-11-04 | 2007-01-31 | Astrazeneca Ab | Nuevas formulaciones de pellets de liberacion modificada para inhibidores de la bomba de protones |
| AR052225A1 (es) * | 2004-11-04 | 2007-03-07 | Astrazeneca Ab | Formulaciones de tabletas de liberacion modificada par inhibidores de la bomba de protones |
| US20060105038A1 (en) * | 2004-11-12 | 2006-05-18 | Eurand Pharmaceuticals Limited | Taste-masked pharmaceutical compositions prepared by coacervation |
| KR20130030305A (ko) * | 2004-11-16 | 2013-03-26 | 엘란 파마 인터내셔널 리미티드 | 주사가능한 나노입자형 올란자핀 제형 |
| WO2006063078A2 (en) * | 2004-12-08 | 2006-06-15 | Elan Corporation, Plc | Topiramate pharmaceuticals composition |
| NZ555842A (en) * | 2004-12-09 | 2010-10-29 | Celgene Corp | Treatment of various conditions of patients with Tourette syndrome, tics, or a family history thereof sing D-threo methylphenidate free from other isomers |
| US20060159766A1 (en) * | 2004-12-15 | 2006-07-20 | Elan Pharma International Limited | Nanoparticulate tacrolimus formulations |
| US20060269596A1 (en) * | 2005-01-12 | 2006-11-30 | Gary Liversidge | Controlled release compositions comprising an acylanilide |
| US20080268043A1 (en) * | 2005-01-26 | 2008-10-30 | Elan Pharma International Limited | Controlled Release Compositions Comprising an Antipsychotic Agent |
| GB0501809D0 (en) * | 2005-01-28 | 2005-03-09 | Pharmakodex Ltd | Anti-migraine formulations |
| WO2006087394A1 (fr) * | 2005-02-21 | 2006-08-24 | Flamel Technologies | Forme pharmaceutique orale de losartan |
| FR2882259A1 (fr) * | 2005-02-21 | 2006-08-25 | Flamel Technologies Sa | Forme pharmaceutique orale multimicroparticulaire a liberation modifiee de losartan |
| FR2884145A1 (fr) * | 2005-04-06 | 2006-10-13 | Flamel Technologies Sa | Forme pharmaceutique orale de losartan |
| FR2882260A1 (fr) * | 2005-02-21 | 2006-08-25 | Flamel Technologies Sa | Forme pharmaceutique orale multimicroparticulaire a liberation modifiee d'antagonistes des recepteurs de l'angiotensine ii |
| US20080254114A1 (en) * | 2005-03-03 | 2008-10-16 | Elan Corporation Plc | Controlled Release Compositions Comprising Heterocyclic Amide Derivative Nanoparticles |
| JP2008534530A (ja) * | 2005-03-29 | 2008-08-28 | エボニック レーム ゲゼルシャフト ミット ベシュレンクテル ハフツング | 活性成分放出に関して調節作用を有する物質を有するペレットを含有している多粒子薬剤形 |
| JP2008535921A (ja) * | 2005-04-12 | 2008-09-04 | エラン・ファルマ・インターナショナル・リミテッド | シクロスポリンを含むナノ粒子および放出調節された組成物 |
| DE112006000873T5 (de) * | 2005-04-12 | 2008-03-06 | Elan Pharma International Ltd. | Zusammensetzungen mit modifizierter Freisetzung, umfassend ein Fluorcytidin-Derivate zur Behandlung von Krebs |
| KR20080007586A (ko) * | 2005-04-12 | 2008-01-22 | 엘란 파마 인터내셔널 리미티드 | 세균감염증의 치료를 위한 세팔로스포린 함유 조절 방출조성물 |
| EP1874272A4 (en) * | 2005-04-13 | 2010-11-10 | Elan Pharma Int Ltd | NANOTEHOUS COMPOSITIONS FROM PROSTAGLANDIN DERIVATIVES WITH CONTROLLED RELEASE |
| US9161918B2 (en) | 2005-05-02 | 2015-10-20 | Adare Pharmaceuticals, Inc. | Timed, pulsatile release systems |
| JP2009514989A (ja) * | 2005-05-10 | 2009-04-09 | エラン コーポレーション ピーエルシー | 改変放出ロキソプロフェン組成物 |
| BRPI0614080A2 (pt) * | 2005-05-16 | 2017-07-25 | Elan Pharma Int Ltd | Composição e método para a preparação de uma cefalosporina nanoparticulada, para o tratamento de doença bacteriana e para a prevenção e/ou tratamento de osteoporose |
| JP2008545808A (ja) * | 2005-05-23 | 2008-12-18 | エラン・ファルマ・インターナショナル・リミテッド | 血小板凝集阻害薬を含むナノ粒子状および制御放出組成物 |
| WO2007037790A2 (en) * | 2005-06-08 | 2007-04-05 | Elan Corporation, Plc | Modified release famciclovir compositions |
| DE112006001606T5 (de) | 2005-06-08 | 2009-07-09 | Elan Pharma International Ltd., Athlone | Nanopartikuläre und eine kontrollierte Freisetzung aufweisende Zusammensetzung, die Cefditoren umfassen |
| JP2009516636A (ja) * | 2005-06-13 | 2009-04-23 | エラン コーポレーション ピーエルシー | 改変放出チクロピジン組成物 |
| US8263561B2 (en) | 2005-06-16 | 2012-09-11 | Amana Pharmaceuticals Corp. | Composition and method for inhibiting, preventing, or ameliorating complications associated with ingestion of a medicinal, chemical, or biological substance or agent |
| WO2007027273A1 (en) * | 2005-06-20 | 2007-03-08 | Elan Pharma International Limited | Nanoparticulate and controlled release compositions comprising aryl-heterocyclic compounds |
| US7241805B2 (en) | 2005-06-27 | 2007-07-10 | Biovail Laboratories, Inc. | Modified release formulations of a bupropion salt |
| CA2616443C (en) * | 2005-07-28 | 2017-10-10 | University Of Hull | Uses of sporopollenin as an antioxidant |
| US8778395B2 (en) * | 2005-08-11 | 2014-07-15 | Andrx Labs, Llc | Diltiazem controlled release formulation and method of manufacture |
| JP2009504748A (ja) * | 2005-08-15 | 2009-02-05 | ユニバーシティ オブ バージニア パテント ファウンデーション | Ｒ（＋）プラミペキソールを用いた神経回復 |
| US9278161B2 (en) | 2005-09-28 | 2016-03-08 | Atrium Medical Corporation | Tissue-separating fatty acid adhesion barrier |
| US9427423B2 (en) | 2009-03-10 | 2016-08-30 | Atrium Medical Corporation | Fatty-acid based particles |
| FR2891459B1 (fr) * | 2005-09-30 | 2007-12-28 | Flamel Technologies Sa | Microparticules a liberation modifiee d'au moins un principe actif et forme galenique orale en comprenant |
| AU2006304889A1 (en) * | 2005-10-14 | 2007-04-26 | H. Lundbeck A/S | Stable pharmaceutical formulations containing escitalopram and bupropion |
| AU2006308635A1 (en) * | 2005-10-14 | 2007-05-10 | H. Lundbeck A/S | Methods of treating central nervous system disorders with a low dose combination of escitalopram and bupropion |
| US20070098791A1 (en) * | 2005-10-31 | 2007-05-03 | Rekhi Gurvinder S | Controlled release compositions comprising a combination of isosorbide dinitrate and hydralazine hydrochloride |
| US20070098796A1 (en) * | 2005-10-31 | 2007-05-03 | Rekhi Gurvinder S | Controlled release compositions comprising a combination of isosorbide dinitrate and hydralazine hydrochrloride |
| WO2007062266A2 (en) * | 2005-11-28 | 2007-05-31 | Marinus Pharmaceuticals | Ganaxolone formulations and methods for the making and use thereof |
| US8357394B2 (en) | 2005-12-08 | 2013-01-22 | Shionogi Inc. | Compositions and methods for improved efficacy of penicillin-type antibiotics |
| US8778924B2 (en) | 2006-12-04 | 2014-07-15 | Shionogi Inc. | Modified release amoxicillin products |
| US20070134322A1 (en) * | 2005-12-14 | 2007-06-14 | Forest Laboratories, Inc. | Modified and pulsatile release pharmaceutical formulations of escitalopram |
| US20070141147A1 (en) * | 2005-12-21 | 2007-06-21 | Auriga Laboratories, Inc. | Sequential release pharmaceutical formulations |
| US10064828B1 (en) | 2005-12-23 | 2018-09-04 | Intellipharmaceutics Corp. | Pulsed extended-pulsed and extended-pulsed pulsed drug delivery systems |
| KR100753480B1 (ko) * | 2006-01-27 | 2007-08-31 | 씨제이 주식회사 | 잘토프로펜 함유 서방성 정제 및 그 제조방법 |
| NZ569984A (en) * | 2006-01-27 | 2011-06-30 | Eurand Inc | Drug delivery systems comprising weakly basic drugs and organic acids |
| KR100762847B1 (ko) * | 2006-01-27 | 2007-10-04 | 씨제이 주식회사 | 멀티플 유닛 타입 서방성 경구 제제 및 그 제조방법 |
| CN103211779B (zh) * | 2006-01-27 | 2016-03-16 | 阿代尔制药股份有限公司 | 包含弱碱性选择性5-羟色胺5-ht3阻断剂和有机酸的药物递送系统 |
| TWI478721B (zh) | 2006-02-09 | 2015-04-01 | Alba Therapeutics Corp | 細胞緊密連接效應劑之配方 |
| US20070212414A1 (en) * | 2006-03-08 | 2007-09-13 | Penwest Pharmaceuticals Co. | Ethanol-resistant sustained release formulations |
| KR20070091960A (ko) * | 2006-03-08 | 2007-09-12 | 주식회사종근당 | 졸피뎀 또는 그의 염을 포함하는 안전한 제어방출형 제제조성물 |
| ATE536867T1 (de) | 2006-03-16 | 2011-12-15 | Tris Pharma Inc | Modifizierte freisetzungsformulierungen mit arznei-ion-austausch-harzkomplexen |
| CA2648280C (en) * | 2006-04-03 | 2014-03-11 | Isa Odidi | Controlled release delivery device comprising an organosol coat |
| US8518926B2 (en) * | 2006-04-10 | 2013-08-27 | Knopp Neurosciences, Inc. | Compositions and methods of using (R)-pramipexole |
| US20070253927A1 (en) * | 2006-04-13 | 2007-11-01 | Gwenaelle Jegou | Cosmetic compositions comprising at least one dielectrophile monomer and at least one radical initiator |
| WO2007123883A2 (en) * | 2006-04-17 | 2007-11-01 | Actavis Group Ptc Ehf | Oral dosage formulations and methods of preparing the same |
| US8299052B2 (en) | 2006-05-05 | 2012-10-30 | Shionogi Inc. | Pharmaceutical compositions and methods for improved bacterial eradication |
| US10960077B2 (en) | 2006-05-12 | 2021-03-30 | Intellipharmaceutics Corp. | Abuse and alcohol resistant drug composition |
| US8846100B2 (en) | 2006-05-12 | 2014-09-30 | Shire Llc | Controlled dose drug delivery system |
| WO2007136664A2 (en) * | 2006-05-16 | 2007-11-29 | Flow Focusing, Inc. | Antibiotic formulation and method of treatment |
| KR20090021169A (ko) | 2006-05-16 | 2009-02-27 | 크놉 뉴로사이언시스 인코포레이티드 | Ｒ(+) 및 ｓ(-) 프라미펙솔을 포함하는 조성물 및 이의 사용 방법 |
| US20080069891A1 (en) | 2006-09-15 | 2008-03-20 | Cima Labs, Inc. | Abuse resistant drug formulation |
| BRPI0713447A2 (pt) * | 2006-06-23 | 2012-03-13 | Elan Pharma International Limited | composição forma de dosagem oral sólida, e, método para o tratamento de dor |
| EP2032139A4 (en) * | 2006-06-23 | 2012-08-22 | Elan Pharma Int Ltd | COMPOSITIONS USING NANOTEHOUS MELOXICAM AND HYDROCODON WITH CONTROLLED RELEASE |
| KR20090031618A (ko) * | 2006-07-12 | 2009-03-26 | 엘란 코포레이션, 피엘씨 | 나노입자형 모다피닐 제제 |
| US20080020032A1 (en) * | 2006-07-21 | 2008-01-24 | Michael Crowley | Hydrophobic abuse deterrent delivery system for hydromorphone |
| US8889184B2 (en) * | 2006-09-07 | 2014-11-18 | Losan Pharma Gmbh | Particulate form of a pharmaceutical composition which is easy to swallow |
| NZ575171A (en) * | 2006-08-31 | 2012-04-27 | Aptalis Pharmatech Inc | Drug delivery systems comprising solid solutions of weakly basic drugs |
| US9744137B2 (en) * | 2006-08-31 | 2017-08-29 | Supernus Pharmaceuticals, Inc. | Topiramate compositions and methods of enhancing its bioavailability |
| US20080064694A1 (en) * | 2006-09-11 | 2008-03-13 | Auriga Laboratories, Inc. | Multi-Phase Release Methscopolamine Compositions |
| WO2008033155A1 (en) * | 2006-09-15 | 2008-03-20 | Auriga Laboratories, Inc. | Kits for prevention and treatment of rhinitis |
| US8445018B2 (en) | 2006-09-15 | 2013-05-21 | Cima Labs Inc. | Abuse resistant drug formulation |
| US20080081067A1 (en) * | 2006-10-03 | 2008-04-03 | Gupta Manishkumar | Sustained release pharmaceutical compositions of venlafaxine and process for preparation thereof |
| US20080085312A1 (en) * | 2006-10-04 | 2008-04-10 | Auriga Laboratories, Inc. | Multi-Phase Release Potassium Guaiacolsulfonate Compositions |
| WO2008043107A2 (en) * | 2006-10-06 | 2008-04-10 | Alba Therapeutics Corporation | Use of tight junction antagonists to treat inflammatory bowel disease |
| SI2124556T1 (sl) | 2006-10-09 | 2015-01-30 | Charleston Laboratories, Inc. | Farmacevtske sestave |
| WO2008052185A2 (en) * | 2006-10-26 | 2008-05-02 | Alba Therapeutics Corp | Materials and methods for the treatment of celiac disease |
| US8642083B2 (en) * | 2006-10-30 | 2014-02-04 | Hanall Biopharma Co., Ltd. | Controlled release complex composition comprising angiotensin-II-receptor blockers and HMG-CoA reductase inhibitors |
| US8394845B2 (en) * | 2006-10-30 | 2013-03-12 | Hanall Biopharma Co., Ltd. | Method of using combination preparation comprising angiotensin-II-receptor blocker and HMG-CoA reductase inhibitor |
| US20110212175A1 (en) * | 2006-10-30 | 2011-09-01 | Hanall Biopharma Co., Ltd. | Combination preparation comprising angiotensin-ii-receptor blocker and hmg-coa reductase inhibitor |
| US9492596B2 (en) | 2006-11-06 | 2016-11-15 | Atrium Medical Corporation | Barrier layer with underlying medical device and one or more reinforcing support structures |
| WO2008057344A2 (en) | 2006-11-06 | 2008-05-15 | Atrium Medical Corporation | Coated surgical mesh |
| EP2394643B1 (en) | 2006-11-17 | 2015-09-02 | Supernus Pharmaceuticals, Inc. | Sustained-release formulations of topiramate |
| AU2007323674B2 (en) | 2006-11-21 | 2013-05-23 | Mcneil-Ppc, Inc. | Modified release analgesic suspensions |
| CA2669815A1 (en) * | 2006-11-28 | 2008-06-05 | Marinus Pharmaceuticals | Nanoparticulate formulations and methods for the making and use thereof |
| US20080131501A1 (en) * | 2006-12-04 | 2008-06-05 | Supernus Pharmaceuticals, Inc. | Enhanced immediate release formulations of topiramate |
| US8524695B2 (en) * | 2006-12-14 | 2013-09-03 | Knopp Neurosciences, Inc. | Modified release formulations of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine and methods of using the same |
| TWI421090B (zh) | 2007-02-20 | 2014-01-01 | Aptalis Pharma Ltd | 穩定之消化酵素組合物 |
| US20080227805A1 (en) * | 2007-02-28 | 2008-09-18 | Abbott Laboratories | Sustained release parenteral formulations of buprenorphine |
| JP2010521496A (ja) | 2007-03-14 | 2010-06-24 | ノップ ニューロサイエンシーズ、インク． | キラル精製置換ベンゾチアゾールジアミンの合成 |
| US9833510B2 (en) * | 2007-06-12 | 2017-12-05 | Johnson & Johnson Consumer Inc. | Modified release solid or semi-solid dosage forms |
| US20090124650A1 (en) * | 2007-06-21 | 2009-05-14 | Endo Pharmaceuticals, Inc. | Method of Treating Pain Utilizing Controlled Release Oxymorphone Pharmaceutical Compositions and Instructions on Effects of Alcohol |
| US20080318994A1 (en) * | 2007-06-21 | 2008-12-25 | Endo Pharmaceuticals, Inc. | Method of Treating Pain Utilizing Controlled Release Oxymorphone Pharmaceutical Compositions and Instruction on Dosing for Renal Impairment |
| US20080318993A1 (en) * | 2007-06-21 | 2008-12-25 | Endo Pharmaceuticals, Inc. | Method of Treating Pain Utilizing Controlled Release Oxymorphone Pharmaceutical Compositions and Instruction on Dosing for Hepatic Impairment |
| US20090060983A1 (en) * | 2007-08-30 | 2009-03-05 | Bunick Frank J | Method And Composition For Making An Orally Disintegrating Dosage Form |
| RU2482839C2 (ru) * | 2007-10-31 | 2013-05-27 | МакНЕЙЛС-ППС, ИНК. | Распадающаяся в полости рта лекарственная форма |
| AU2008335809A1 (en) | 2007-12-06 | 2009-06-18 | Durect Corporation | Methods useful for the treatment of pain, arthritic conditions, or inflammation associated with a chronic condition |
| CA2711014C (en) | 2007-12-28 | 2018-10-23 | Impax Laboratories, Inc. | Controlled release formulations of levodopa and uses thereof |
| JP5714910B2 (ja) | 2008-01-09 | 2015-05-07 | チャールストン ラボラトリーズ，インコーポレイテッド | 薬学的組成物 |
| US20100137442A2 (en) * | 2008-02-01 | 2010-06-03 | Xenoport, Inc. | Sustained Release Particulate Oral Dosage Forms of (R)-Baclofen and Methods of Treatment |
| US10087493B2 (en) | 2008-03-07 | 2018-10-02 | Aptalis Pharma Canada Ulc | Method for detecting infectious parvovirus in pharmaceutical preparations |
| WO2009114648A1 (en) * | 2008-03-11 | 2009-09-17 | Depomed Inc. | Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic |
| US8372432B2 (en) * | 2008-03-11 | 2013-02-12 | Depomed, Inc. | Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic |
| US8133506B2 (en) * | 2008-03-12 | 2012-03-13 | Aptalis Pharmatech, Inc. | Drug delivery systems comprising weakly basic drugs and organic acids |
| CA2627198A1 (en) * | 2008-03-27 | 2009-09-27 | Pharmascience Inc. | Methylphenidate extended release therapeutic drug delivery system |
| US20090311335A1 (en) * | 2008-06-12 | 2009-12-17 | Scott Jenkins | Combination of a triptan and an nsaid |
| GB0812513D0 (en) * | 2008-07-09 | 2008-08-13 | Univ Hull | Delivery vehicle |
| US20110190356A1 (en) * | 2008-08-19 | 2011-08-04 | Knopp Neurosciences Inc. | Compositions and Methods of Using (R)- Pramipexole |
| DE102008048729A1 (de) * | 2008-09-24 | 2010-03-25 | Add Technologies Ltd Advanced Drug Delivery | Multipartikuläre Tabletten und Verfahren zur deren Herstellung |
| US20100260844A1 (en) | 2008-11-03 | 2010-10-14 | Scicinski Jan J | Oral pharmaceutical dosage forms |
| US8465768B2 (en) | 2008-11-07 | 2013-06-18 | Samyang Biopharmaceuticals Corporation | Pharmaceutical compositions for release control of methylphenidate |
| US20110217371A1 (en) * | 2008-11-10 | 2011-09-08 | Amorepacific Corporation | Controlled-release microparticles and method of preparing same |
| US8551517B2 (en) * | 2008-12-16 | 2013-10-08 | Kimberly-Clark Worldwide, Inc. | Substrates providing multiple releases of active agents |
| AU2009332963B2 (en) | 2008-12-31 | 2015-02-05 | Upsher-Smith Laboratories, Llc | Opioid-containing oral pharmaceutical compositions and methods |
| LT2395840T (lt) | 2009-02-13 | 2020-07-10 | Romark Laboratories, L.C. | Nitazoksanido kontroliuojamo atpalaidavimo farmacinės kompozicijos |
| DK3045043T3 (da) | 2009-02-26 | 2020-08-03 | Relmada Therapeutics Inc | Orale farmaceutiske sammensætninger af 3-hydroxy-n-methylmorphinan med forlænget frigivelse og fremgangsmåde til anvendelse |
| CN105581984A (zh) * | 2009-04-09 | 2016-05-18 | 阿尔科米斯制药爱尔兰有限公司 | 药物递送组合物 |
| KR20120022984A (ko) * | 2009-04-21 | 2012-03-12 | 셀렉타 바이오사이언시즈, 인크. | Ｔｈ１ 편향 반응을 제공하는 면역나노치료법 |
| MX360019B (es) * | 2009-04-24 | 2018-10-15 | Iceutica Pty Ltd | Una formulación novedosa de metaxalona. |
| MX357630B (es) | 2009-05-27 | 2018-07-17 | Selecta Biosciences Inc | Nanoportadores sintéticos objetivo con liberación sensible al ph de agentes inmunomoduladores. |
| US20110003005A1 (en) * | 2009-07-06 | 2011-01-06 | Gopi Venkatesh | Methods of Treating PDNV and PONV with Extended Release Ondansetron Compositions |
| WO2011006012A1 (en) | 2009-07-08 | 2011-01-13 | Charleston Laboratories Inc. | Pharmaceutical compositions |
| TW201117812A (en) | 2009-08-05 | 2011-06-01 | Idenix Pharmaceuticals Inc | Macrocyclic serine protease inhibitors |
| US20110038910A1 (en) | 2009-08-11 | 2011-02-17 | Atrium Medical Corporation | Anti-infective antimicrobial-containing biomaterials |
| EP2473195A4 (en) * | 2009-08-31 | 2013-01-16 | Depomed Inc | PHARMACEUTICAL MAGNETIC RELEASE COMPOSITIONS FOR IMMEDIATE AND EXTENDED RELEASE OF ACETAMINOPHES |
| BR112012008317A2 (pt) | 2009-09-17 | 2016-03-22 | Upsher Smith Lab Inc | produto de liberação sustentada compreendendo uma combinação de uma amina não-opioide e uma droga anti-inflamatória não-esteroidal |
| US8313768B2 (en) | 2009-09-24 | 2012-11-20 | Mcneil-Ppc, Inc. | Manufacture of tablet having immediate release region and sustained release region |
| US20110318411A1 (en) | 2010-06-24 | 2011-12-29 | Luber Joseph R | Multi-layered orally disintegrating tablet and the manufacture thereof |
| US20110070286A1 (en) * | 2009-09-24 | 2011-03-24 | Andreas Hugerth | Process for the manufacture of nicotine-comprising chewing gum and nicotine-comprising chewing gum manufactured according to said process |
| US8871263B2 (en) * | 2009-09-24 | 2014-10-28 | Mcneil-Ppc, Inc. | Manufacture of tablet in a die utilizing radiofrequency energy and meltable binder |
| WO2011056764A1 (en) | 2009-11-05 | 2011-05-12 | Ambit Biosciences Corp. | Isotopically enriched or fluorinated imidazo[2,1-b][1,3]benzothiazoles |
| CN102958515A (zh) | 2009-12-02 | 2013-03-06 | 阿普塔利斯制药有限公司 | 非索非那定微胶囊及含有非索非那定微胶囊的组合物 |
| KR20120118008A (ko) | 2009-12-18 | 2012-10-25 | 아이데닉스 파마슈티칼스, 인코포레이티드 | 5,5-융합 아릴렌 또는 헤테로아릴렌 간염 ｃ 바이러스 억제제 |
| US8597681B2 (en) | 2009-12-22 | 2013-12-03 | Mallinckrodt Llc | Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans |
| US9198861B2 (en) | 2009-12-22 | 2015-12-01 | Mallinckrodt Llc | Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans |
| WO2011094890A1 (en) | 2010-02-02 | 2011-08-11 | Argusina Inc. | Phenylalanine derivatives and their use as non-peptide glp-1 receptor modulators |
| WO2011112689A2 (en) | 2010-03-11 | 2011-09-15 | Ambit Biosciences Corp. | Saltz of an indazolylpyrrolotriazine |
| US9186642B2 (en) | 2010-04-28 | 2015-11-17 | The Procter & Gamble Company | Delivery particle |
| US9993793B2 (en) | 2010-04-28 | 2018-06-12 | The Procter & Gamble Company | Delivery particles |
| WO2011143120A1 (en) | 2010-05-11 | 2011-11-17 | Cima Labs Inc. | Alcoholres i stant metoprolol - containing extended - release oral dosage forms |
| US9012511B2 (en) | 2010-05-19 | 2015-04-21 | Alkermes Pharma Ireland Limited | Nanoparticulate cinacalcet compositions |
| EA030813B1 (ru) | 2010-05-26 | 2018-10-31 | Селекта Байосайенсиз, Инк | Способы генерации антительного иммунного ответа и увеличения местной индукции иммунных цитокинов при использовании синтетических наноносителей, соединенных с адъювантами |
| MX361138B (es) * | 2010-06-16 | 2018-11-28 | Takeda Pharmaceuticals Usa Inc | Formas novedosas de dosificacion de liberacion modificada de inhibidor de xantina oxidorreductasa o inhibidores de xantina oxidasa. |
| WO2012009707A2 (en) | 2010-07-16 | 2012-01-19 | Atrium Medical Corporation | Composition and methods for altering the rate of hydrolysis of cured oil-based materials |
| US9907767B2 (en) | 2010-08-03 | 2018-03-06 | Velicept Therapeutics, Inc. | Pharmaceutical compositions and the treatment of overactive bladder |
| US8912324B2 (en) | 2010-09-01 | 2014-12-16 | Ambit Biosciences Corporation | Optically active pyrazolylaminoquinazoline, and pharmaceutical compositions and methods of use thereof |
| CN103270030B (zh) | 2010-09-01 | 2016-01-20 | 埃姆比特生物科学公司 | 吡唑基氨基喹唑啉的氢溴酸盐 |
| CN101933913A (zh) * | 2010-09-16 | 2011-01-05 | 孙卫东 | 一种盐酸右哌甲酯双释放制剂及其制备方法 |
| WO2012040710A2 (en) | 2010-09-24 | 2012-03-29 | Case Western Reserve University | Stabilized nanobubbles for diagnostic and therapeutic applications |
| PT2621476E (pt) | 2010-10-01 | 2014-10-16 | Aptalis Pharma Ltd | Formulações de pancrelipase de baixa potência com revestimento entérico |
| JP2014500275A (ja) | 2010-12-06 | 2014-01-09 | フォリカ，インコーポレイテッド | 禿頭症を治療するため、および毛髪の成長を促進するための方法 |
| WO2012080050A1 (en) | 2010-12-14 | 2012-06-21 | F. Hoffmann-La Roche Ag | Solid forms of a phenoxybenzenesulfonyl compound |
| WO2012106299A1 (en) | 2011-01-31 | 2012-08-09 | Celgene Corporation | Pharmaceutical compositions of cytidine analogs and methods of use thereof |
| TW201309690A (zh) | 2011-02-10 | 2013-03-01 | Idenix Pharmaceuticals Inc | 巨環絲胺酸蛋白酶抑制劑，其醫藥組合物及其於治療ｈｃｖ感染之用途 |
| US8287903B2 (en) | 2011-02-15 | 2012-10-16 | Tris Pharma Inc | Orally effective methylphenidate extended release powder and aqueous suspension product |
| US9283214B2 (en) | 2011-03-23 | 2016-03-15 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
| US11241391B2 (en) | 2011-03-23 | 2022-02-08 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
| US10905652B2 (en) | 2011-03-23 | 2021-02-02 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
| PT2688557T (pt) | 2011-03-23 | 2017-11-23 | Ironshore Pharmaceuticals & Dev Inc | Métodos e composições para o tratamento de distúrbio de défice de atenção |
| US9119809B2 (en) | 2011-03-23 | 2015-09-01 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
| US10292937B2 (en) | 2011-03-23 | 2019-05-21 | Ironshore Pharmaceuticals & Development, Inc. | Methods of treatment of attention deficit hyperactivity disorder |
| US9603809B2 (en) | 2011-03-23 | 2017-03-28 | Ironshore Pharmaceuticals & Development, Inc. | Methods of treatment of attention deficit hyperactivity disorder |
| US8916588B2 (en) | 2011-03-23 | 2014-12-23 | Ironshore Pharmaceuticals & Development, Inc. | Methods for treatment of attention deficit hyperactivity disorder |
| US8927010B2 (en) | 2011-03-23 | 2015-01-06 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
| US9498447B2 (en) | 2011-03-23 | 2016-11-22 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
| JP6320912B2 (ja) * | 2011-03-25 | 2018-05-09 | セレクタ バイオサイエンシーズ インコーポレーテッドＳｅｌｅｃｔａ Ｂｉｏｓｃｉｅｎｃｅｓ，Ｉｎｃ． | 浸透圧媒介性放出合成ナノ担体 |
| US20120252721A1 (en) | 2011-03-31 | 2012-10-04 | Idenix Pharmaceuticals, Inc. | Methods for treating drug-resistant hepatitis c virus infection with a 5,5-fused arylene or heteroarylene hepatitis c virus inhibitor |
| EP2694031B1 (en) | 2011-04-07 | 2015-07-08 | The Procter and Gamble Company | Conditioner compositions with increased deposition of polyacrylate microcapsules |
| MX2013010983A (es) | 2011-04-07 | 2013-10-30 | Procter & Gamble | Composiciones de champu con deposito mejorado de microcapsulas de poliacrilato. |
| US9162085B2 (en) | 2011-04-07 | 2015-10-20 | The Procter & Gamble Company | Personal cleansing compositions with increased deposition of polyacrylate microcapsules |
| US8741885B1 (en) | 2011-05-17 | 2014-06-03 | Mallinckrodt Llc | Gastric retentive extended release pharmaceutical compositions |
| US8658631B1 (en) | 2011-05-17 | 2014-02-25 | Mallinckrodt Llc | Combination composition comprising oxycodone and acetaminophen for rapid onset and extended duration of analgesia |
| US8858963B1 (en) | 2011-05-17 | 2014-10-14 | Mallinckrodt Llc | Tamper resistant composition comprising hydrocodone and acetaminophen for rapid onset and extended duration of analgesia |
| WO2013019648A1 (en) | 2011-07-29 | 2013-02-07 | Selecta Biosciences, Inc. | Control of antibody responses to synthetic nanocarriers |
| RU2016119726A (ru) | 2011-08-08 | 2018-11-02 | Апталис Фарма Лтд. | Способ проведения теста на растворение твердых композиций, содержащих пищеварительные ферменты |
| US9512096B2 (en) | 2011-12-22 | 2016-12-06 | Knopp Biosciences, LLP | Synthesis of amine substituted 4,5,6,7-tetrahydrobenzothiazole compounds |
| CN102429884A (zh) * | 2011-12-29 | 2012-05-02 | 天津市嵩锐医药科技有限公司 | 盐酸哌甲酯口腔崩解药物组合物 |
| CN104302640A (zh) | 2012-03-16 | 2015-01-21 | 埃克希金医药品有限公司 | 3,5-二氨基吡唑激酶抑制剂 |
| US9233491B2 (en) | 2012-05-01 | 2016-01-12 | Johnson & Johnson Consumer Inc. | Machine for production of solid dosage forms |
| US9445971B2 (en) | 2012-05-01 | 2016-09-20 | Johnson & Johnson Consumer Inc. | Method of manufacturing solid dosage form |
| US9511028B2 (en) | 2012-05-01 | 2016-12-06 | Johnson & Johnson Consumer Inc. | Orally disintegrating tablet |
| US9867880B2 (en) | 2012-06-13 | 2018-01-16 | Atrium Medical Corporation | Cured oil-hydrogel biomaterial compositions for controlled drug delivery |
| MX2014015310A (es) | 2012-06-15 | 2015-07-06 | Found Biomedical Res & Innov | Agente profilactico y/o terapeutico para el deterioro cognoscitivo leve. |
| WO2014011830A1 (en) | 2012-07-12 | 2014-01-16 | Mallinckrodt Llc | Extended release, abuse deterrent pharmaceutical compositions |
| US10322120B2 (en) | 2012-07-31 | 2019-06-18 | Persion Pharmaceuticals Llc | Treating pain in patients with hepatic impairment |
| US20140161879A1 (en) * | 2012-07-31 | 2014-06-12 | Zogenix, Inc. | Treating pain in patients with hepatic impairment |
| BR112015003120B1 (pt) | 2012-08-15 | 2022-08-09 | Tris Pharma , Inc | Tablete mastigável de liberação estendida de metilfenidato e seu uso |
| US9662313B2 (en) | 2013-02-28 | 2017-05-30 | Knopp Biosciences Llc | Compositions and methods for treating amyotrophic lateral sclerosis in responders |
| WO2014144975A1 (en) | 2013-03-15 | 2014-09-18 | Durect Corporation | Compositions with a rheological modifier to reduce dissolution variability |
| EP2994112A1 (en) * | 2013-03-29 | 2016-03-16 | Wockhardt Limited | Modified release pharmaceutical compositions of dexmethylphenidate or salts thereof |
| US10434194B2 (en) | 2013-06-20 | 2019-10-08 | Case Western Reserve University | PSMA targeted nanobubbles for diagnostic and therapeutic applications |
| ES3043076T3 (en) | 2013-07-12 | 2025-11-24 | Areteia Therapeutics Inc | Treating elevated levels of eosinophils and/or basophils |
| US9468630B2 (en) | 2013-07-12 | 2016-10-18 | Knopp Biosciences Llc | Compositions and methods for treating conditions related to increased eosinophils |
| WO2015020943A2 (en) | 2013-08-09 | 2015-02-12 | Aptalis Pharma Ltd. | Digestive enzyme composition suitable for enteral administration |
| EP3038467B1 (en) | 2013-08-13 | 2020-07-29 | Knopp Biosciences LLC | Compositions and methods for treating plasma cell disorders and b-cell prolymphocytic disorders |
| US9763918B2 (en) | 2013-08-13 | 2017-09-19 | Knopp Biosciences Llc | Compositions and methods for treating chronic urticaria |
| NZ631142A (en) | 2013-09-18 | 2016-03-31 | Axikin Pharmaceuticals Inc | Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors |
| EP3046924A1 (en) | 2013-09-20 | 2016-07-27 | IDENIX Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| US10987313B2 (en) | 2013-10-07 | 2021-04-27 | Impax Laboratories, Llc | Muco-adhesive, controlled release formulations of levodopa and/or esters of levodopa and uses thereof |
| CA2926082C (en) | 2013-10-07 | 2022-06-14 | Impax Laboratories, Inc. | Muco-adhesive, controlled release formulations of levodopa and/or esters of levodopa and uses thereof |
| WO2015065547A1 (en) | 2013-10-31 | 2015-05-07 | Cima Labs Inc. | Immediate release abuse-deterrent granulated dosage forms |
| WO2015065497A1 (en) * | 2013-11-04 | 2015-05-07 | Schultz Jack William | Treatment of cognitive, emotional and mental ailments and disorders |
| ES2750323T3 (es) | 2014-01-10 | 2020-03-25 | Johnson & Johnson Consumer Inc | Método para la fabricación de un comprimido mediante radiofrecuencia y partículas recubiertas con pérdida |
| WO2015134560A1 (en) | 2014-03-05 | 2015-09-11 | Idenix Pharmaceuticals, Inc. | Solid forms of a flaviviridae virus inhibitor compound and salts thereof |
| TWI705967B (zh) | 2014-03-20 | 2020-10-01 | 美商卡佩拉醫療公司 | 苯并咪唑衍生物及其醫藥組合物及使用方法 |
| JP6577012B2 (ja) | 2014-03-20 | 2019-09-18 | カペラ セラピューティクス，インコーポレーテッド | 癌の治療のためのｅｒｂｂチロシンキナーゼ阻害剤としてのベンゾイミダゾール誘導体 |
| JP2017519490A (ja) | 2014-06-19 | 2017-07-20 | アプタリス ファルマ リミテッド | 膵臓抽出物からのウイルス汚染の除去方法 |
| KR101686986B1 (ko) * | 2014-07-28 | 2016-12-16 | 에스케이케미칼주식회사 | 류프로라이드를 포함하는 속효성과 지속성을 동시에 갖는 약제학적 조성물 |
| US9132096B1 (en) | 2014-09-12 | 2015-09-15 | Alkermes Pharma Ireland Limited | Abuse resistant pharmaceutical compositions |
| CA2959186C (en) | 2014-09-19 | 2020-03-24 | The Procter & Gamble Company | Pulsed release phenylephrine dosage forms |
| CA2936740C (en) | 2014-10-31 | 2017-10-10 | Purdue Pharma | Methods and compositions particularly for treatment of attention deficit disorder |
| GB201420306D0 (en) | 2014-11-14 | 2014-12-31 | Bio Images Drug Delivery Ltd | Compositions |
| EP3226849A4 (en) | 2014-12-03 | 2018-05-09 | Velicept Therapeutics, Inc. | Compositions and methods of using modified release solabegron for lower urinary tract symptoms |
| HUE049801T2 (hu) | 2014-12-23 | 2020-10-28 | Sma Therapeutics Inc | 3,5-diaminopirazol kináz inhibitorok |
| US11590228B1 (en) | 2015-09-08 | 2023-02-28 | Tris Pharma, Inc | Extended release amphetamine compositions |
| CN108135838A (zh) | 2015-10-16 | 2018-06-08 | 马瑞纳斯制药公司 | 包含纳米粒的可注射神经类固醇制剂 |
| US10065922B2 (en) | 2015-10-23 | 2018-09-04 | Velicept Therapeutics, Inc. | Solabegron zwitterion and uses thereof |
| US20170296476A1 (en) * | 2016-04-15 | 2017-10-19 | Grünenthal GmbH | Modified release abuse deterrent dosage forms |
| US10335405B1 (en) | 2016-05-04 | 2019-07-02 | Patheon Softgels, Inc. | Non-burst releasing pharmaceutical composition |
| US20170348288A1 (en) * | 2016-06-03 | 2017-12-07 | Velicept Therapeutics, Inc. | Dosing regimens for beta-3 adrenoceptor agonists and anti-muscarinic agents for the treatment and prevention of lower urinary tract symptoms and overactive bladder |
| CA3028450A1 (en) | 2016-07-06 | 2018-01-11 | Durect Corporation | Oral dosage form with drug composition, barrier layer and drug layer |
| CN109715151A (zh) | 2016-08-11 | 2019-05-03 | 奥维德医疗公司 | 用于治疗癫痫性紊乱的方法和组合物 |
| US10391105B2 (en) | 2016-09-09 | 2019-08-27 | Marinus Pharmaceuticals Inc. | Methods of treating certain depressive disorders and delirium tremens |
| KR20190107655A (ko) * | 2016-11-01 | 2019-09-20 | 네오스 테라퓨틱스, 엘피 | Adhd의 치료를 위한 메틸페니데이트의 효과적인 아동 투여 |
| US10278930B2 (en) | 2017-03-16 | 2019-05-07 | The Procter & Gamble Company | Method for relieving sinus congestion |
| US10493026B2 (en) | 2017-03-20 | 2019-12-03 | Johnson & Johnson Consumer Inc. | Process for making tablet using radiofrequency and lossy coated particles |
| US10555986B2 (en) * | 2017-03-23 | 2020-02-11 | Instituto De Capacitación E Investigación Del Plás | Dietary supplement derived from natural prodcuts by hot melt extrusion (HME) processing |
| US12458592B1 (en) | 2017-09-24 | 2025-11-04 | Tris Pharma, Inc. | Extended release amphetamine tablets |
| US11590081B1 (en) | 2017-09-24 | 2023-02-28 | Tris Pharma, Inc | Extended release amphetamine tablets |
| US20190381056A1 (en) | 2018-06-17 | 2019-12-19 | Axsome Therapeutics, Inc. | Compositions for delivery of reboxetine |
| US20200147093A1 (en) | 2018-10-15 | 2020-05-14 | Axsome Therapeutics, Inc. | Use of esreboxetine to treat nervous system disorders such as fibromyalgia |
| US11020402B2 (en) | 2018-10-15 | 2021-06-01 | Axsome Therapeutics, Inc. | Use of reboxetine to treat narcolepsy |
| US10722473B2 (en) | 2018-11-19 | 2020-07-28 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
| WO2020104955A1 (en) * | 2018-11-20 | 2020-05-28 | Dr. Reddy’S Laboratories Limited | Pharmaceutical compositions of acotiamide and proton pump inhibitor |
| WO2020118142A1 (en) | 2018-12-07 | 2020-06-11 | Marinus Pharmaceuticals, Inc. | Ganaxolone for use in prophylaxis and treatment of pospartum depression |
| AU2019414333A1 (en) * | 2018-12-28 | 2021-08-05 | Panda Consulting Llc | Short-acting selective glucocorticoid receptor modulators |
| US11324707B2 (en) | 2019-05-07 | 2022-05-10 | Clexio Biosciences Ltd. | Abuse-deterrent dosage forms containing esketamine |
| US20220062200A1 (en) | 2019-05-07 | 2022-03-03 | Clexio Biosciences Ltd. | Abuse-deterrent dosage forms containing esketamine |
| CN114728012A (zh) | 2019-08-05 | 2022-07-08 | 马瑞纳斯制药公司 | 用于治疗癫痫持续状态的加奈索酮 |
| MX2022006014A (es) | 2019-12-06 | 2022-06-22 | Marinus Pharmaceuticals Inc | Ganaxolona para uso en el tratamiento del complejo de esclerosis tuberosa. |
| CN116323892A (zh) | 2020-10-16 | 2023-06-23 | 宝洁公司 | 具有至少两个包封物群体的消费产品组合物 |
| JP7719177B2 (ja) | 2020-10-16 | 2025-08-05 | ザ プロクター アンド ギャンブル カンパニー | 封入体の集団を含む消費者製品組成物 |
| US12486478B2 (en) | 2020-10-16 | 2025-12-02 | The Procter & Gamble Company | Consumer products comprising delivery particles with high core:wall ratios |
| US12194150B2 (en) | 2020-12-22 | 2025-01-14 | Amneal Pharmaceuticals Llc | Levodopa dosing regimen |
| US11986449B2 (en) | 2020-12-22 | 2024-05-21 | Amneal Pharmaceuticals Llc | Levodopa dosing regimen |
| CN114022146A (zh) * | 2021-11-03 | 2022-02-08 | 杭州每刻科技有限公司 | 基于Jasper的网银付款文件的生成方法及系统 |
| US12303604B1 (en) | 2024-10-16 | 2025-05-20 | Currax Pharmaceuticals Llc | Pharmaceutical formulations comprising naltrexone and/or bupropion |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5445829A (en) * | 1989-05-05 | 1995-08-29 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
Family Cites Families (213)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1082206A (en) | 1963-07-02 | 1967-09-06 | Applic Chimiques D Etudes & De | Improved antibiotic medicine |
| US4330626A (en) | 1980-03-19 | 1982-05-18 | The Enzyme Center, Inc. | Method of preparing high-activity, low-bacteria, urease enzyme |
| US4539199A (en) | 1981-01-14 | 1985-09-03 | Egyt Gyogyszervegyeszeti Gyar | Sustained release pharmaceutical compositions |
| JPS5826816A (ja) | 1981-08-11 | 1983-02-17 | Teisan Seiyaku Kk | 球形顆粒からなる持続性複合顆粒剤 |
| DE3279999D1 (en) * | 1981-09-30 | 1989-11-30 | Nat Res Dev | Compositions comprising encapsulated particles |
| DK150008C (da) * | 1981-11-20 | 1987-05-25 | Benzon As Alfred | Fremgangsmaade til fremstilling af et farmaceutisk oralt polydepotpraeparat |
| DE3405378A1 (de) | 1984-02-15 | 1985-08-22 | Röhm GmbH, 6100 Darmstadt | Arzneimittelueberzug |
| US4826689A (en) | 1984-05-21 | 1989-05-02 | University Of Rochester | Method for making uniformly sized particles from water-insoluble organic compounds |
| US4851228A (en) * | 1984-06-20 | 1989-07-25 | Merck & Co., Inc. | Multiparticulate controlled porosity osmotic |
| US4783484A (en) | 1984-10-05 | 1988-11-08 | University Of Rochester | Particulate composition and use thereof as antimicrobial agent |
| IE58110B1 (en) | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
| NL8500724A (nl) | 1985-03-13 | 1986-10-01 | Univ Groningen | Inrichtingen voor geregelde afgifte van werkzame stoffen, alsmede werkwijze ter vervaardiging daarvan. |
| US4728512A (en) | 1985-05-06 | 1988-03-01 | American Home Products Corporation | Formulations providing three distinct releases |
| EP0212747B1 (en) | 1985-08-16 | 1991-04-10 | The Procter & Gamble Company | Drug particles having constant release and immediate release |
| US4892742A (en) | 1985-11-18 | 1990-01-09 | Hoffmann-La Roche Inc. | Controlled release compositions with zero order release |
| US4971790A (en) * | 1986-02-07 | 1990-11-20 | Alza Corporation | Dosage form for lessening irritation of mocusa |
| US4904476A (en) * | 1986-03-04 | 1990-02-27 | American Home Products Corporation | Formulations providing three distinct releases |
| US4794001A (en) | 1986-03-04 | 1988-12-27 | American Home Products Corporation | Formulations providing three distinct releases |
| US4986987A (en) * | 1986-05-09 | 1991-01-22 | Alza Corporation | Pulsed drug delivery |
| IT1200178B (it) * | 1986-07-23 | 1989-01-05 | Alfa Farmaceutici Spa | Formulazioni galeniche a cessione programmata contenenti farmaci ad attivita' antiflogistica |
| US6024983A (en) | 1986-10-24 | 2000-02-15 | Southern Research Institute | Composition for delivering bioactive agents for immune response and its preparation |
| IT1201136B (it) | 1987-01-13 | 1989-01-27 | Resa Farma | Compressa per uso farmaceutico atta al rilascio in tempi successivi di sostanze attive |
| US4948586A (en) | 1987-11-02 | 1990-08-14 | Lim Technology Laboratories, Inc. | Microencapsulated insecticidal pathogens |
| US4844896A (en) | 1987-11-02 | 1989-07-04 | Lim Technology Laboratories, Inc. | Microencapsulated insecticidal pathogens |
| US4971805A (en) | 1987-12-23 | 1990-11-20 | Teysan Pharmaceuticals Co., Ltd. | Slow-releasing granules and long acting mixed granules comprising the same |
| US5460817A (en) | 1988-01-19 | 1995-10-24 | Allied Colloids Ltd. | Particulate composition comprising a core of matrix polymer with active ingredient distributed therein |
| EP0406315B1 (en) | 1988-03-24 | 1992-11-11 | Bukh Meditec A/S | Controlled release composition |
| MC2025A1 (fr) | 1988-04-20 | 1990-04-25 | Asta Pharma Ag | Medicament contenant de l'azelastine et capable de liberer celle-ci de facon controlee |
| FR2634376B1 (fr) | 1988-07-21 | 1992-04-17 | Farmalyoc | Nouvelle forme unitaire, solide et poreuse comprenant des microparticules et/ou des nanoparticules, ainsi que sa preparation |
| US5330766A (en) | 1989-01-06 | 1994-07-19 | F. H. Faulding & Co. Limited | Sustained release pharmaceutical composition |
| US5196203A (en) | 1989-01-06 | 1993-03-23 | F. H. Faulding & Co. Limited | Theophylline dosage form |
| US5202128A (en) | 1989-01-06 | 1993-04-13 | F. H. Faulding & Co. Limited | Sustained release pharmaceutical composition |
| US4956182A (en) * | 1989-03-16 | 1990-09-11 | Bristol-Myers Company | Direct compression cholestyramine tablet and solvent-free coating therefor |
| JPH0674206B2 (ja) | 1989-12-28 | 1994-09-21 | 田辺製薬株式会社 | 放出制御型製剤およびその製法 |
| IE66933B1 (en) * | 1990-01-15 | 1996-02-07 | Elan Corp Plc | Controlled absorption naproxen formulation for once-daily administration |
| US5229131A (en) * | 1990-02-05 | 1993-07-20 | University Of Michigan | Pulsatile drug delivery system |
| US5158777A (en) * | 1990-02-16 | 1992-10-27 | E. R. Squibb & Sons, Inc. | Captopril formulation providing increased duration of activity |
| JPH04234812A (ja) * | 1990-03-16 | 1992-08-24 | Yamanouchi Pharmaceut Co Ltd | 持続性製剤用顆粒 |
| GB9010431D0 (en) | 1990-05-09 | 1990-06-27 | Mead Corp | Wraparound multipack with carrying handle |
| IE61651B1 (en) | 1990-07-04 | 1994-11-16 | Zambon Spa | Programmed release oral solid pharmaceutical dosage form |
| US5156850A (en) | 1990-08-31 | 1992-10-20 | Alza Corporation | Dosage form for time-varying patterns of drug delivery |
| US5232705A (en) * | 1990-08-31 | 1993-08-03 | Alza Corporation | Dosage form for time-varying patterns of drug delivery |
| US5102668A (en) | 1990-10-05 | 1992-04-07 | Kingaform Technology, Inc. | Sustained release pharmaceutical preparation using diffusion barriers whose permeabilities change in response to changing pH |
| US5552160A (en) | 1991-01-25 | 1996-09-03 | Nanosystems L.L.C. | Surface modified NSAID nanoparticles |
| AU642066B2 (en) | 1991-01-25 | 1993-10-07 | Nanosystems L.L.C. | X-ray contrast compositions useful in medical imaging |
| US5145684A (en) * | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
| US5399363A (en) | 1991-01-25 | 1995-03-21 | Eastman Kodak Company | Surface modified anticancer nanoparticles |
| US5387421A (en) | 1991-01-31 | 1995-02-07 | Tsrl, Inc. | Multi stage drug delivery system |
| GEP19971086B (en) | 1991-02-22 | 1997-12-02 | Tillotts Pharma Ag | Peroral Pharmaceutically Dispensed Form for Selective Introducing of the Medicine into the Intestine |
| GB9104854D0 (en) | 1991-03-07 | 1991-04-17 | Reckitt & Colmann Prod Ltd | Sustained release compositions |
| US5286497A (en) * | 1991-05-20 | 1994-02-15 | Carderm Capital L.P. | Diltiazem formulation |
| ZA923474B (en) * | 1991-05-20 | 1993-01-27 | Marion Merrell Dow Inc | Diltiazem formulation |
| EP0593627A1 (en) | 1991-07-05 | 1994-04-27 | The University Of Rochester | Ultrasmall non-aggregated porous particles entrapping gas-bubbles |
| US5226902A (en) | 1991-07-30 | 1993-07-13 | University Of Utah | Pulsatile drug delivery device using stimuli sensitive hydrogel |
| DE69229881T2 (de) | 1991-10-04 | 1999-12-09 | Yoshitomi Pharmaceutical Industries, Ltd. | Tablette mit verzögerter freisetzung |
| DE69222006T2 (de) * | 1991-10-30 | 1998-01-22 | Glaxo Group Ltd | Mehrschichtzusammensetzungen enthaltend Histamin- oder Serotonin- Antagonisten |
| US5162117A (en) | 1991-11-22 | 1992-11-10 | Schering Corporation | Controlled release flutamide composition |
| US5580578A (en) * | 1992-01-27 | 1996-12-03 | Euro-Celtique, S.A. | Controlled release formulations coated with aqueous dispersions of acrylic polymers |
| US5262173A (en) * | 1992-03-02 | 1993-11-16 | American Cyanamid Company | Pulsatile once-a-day delivery systems for minocycline |
| US5260068A (en) | 1992-05-04 | 1993-11-09 | Anda Sr Pharmaceuticals Inc. | Multiparticulate pulsatile drug delivery system |
| US5330759A (en) | 1992-08-26 | 1994-07-19 | Sterling Winthrop Inc. | Enteric coated soft capsules and method of preparation thereof |
| AU660852B2 (en) | 1992-11-25 | 1995-07-06 | Elan Pharma International Limited | Method of grinding pharmaceutical substances |
| US5260069A (en) | 1992-11-27 | 1993-11-09 | Anda Sr Pharmaceuticals Inc. | Pulsatile particles drug delivery system |
| US5349957A (en) | 1992-12-02 | 1994-09-27 | Sterling Winthrop Inc. | Preparation and magnetic properties of very small magnetite-dextran particles |
| US5298262A (en) | 1992-12-04 | 1994-03-29 | Sterling Winthrop Inc. | Use of ionic cloud point modifiers to prevent particle aggregation during sterilization |
| US5346702A (en) | 1992-12-04 | 1994-09-13 | Sterling Winthrop Inc. | Use of non-ionic cloud point modifiers to minimize nanoparticle aggregation during sterilization |
| US5302401A (en) | 1992-12-09 | 1994-04-12 | Sterling Winthrop Inc. | Method to reduce particle size growth during lyophilization |
| US5340564A (en) | 1992-12-10 | 1994-08-23 | Sterling Winthrop Inc. | Formulations comprising olin 10-G to prevent particle aggregation and increase stability |
| US5336507A (en) | 1992-12-11 | 1994-08-09 | Sterling Winthrop Inc. | Use of charged phospholipids to reduce nanoparticle aggregation |
| US5429824A (en) | 1992-12-15 | 1995-07-04 | Eastman Kodak Company | Use of tyloxapole as a nanoparticle stabilizer and dispersant |
| US5352459A (en) | 1992-12-16 | 1994-10-04 | Sterling Winthrop Inc. | Use of purified surface modifiers to prevent particle aggregation during sterilization |
| US5326552A (en) | 1992-12-17 | 1994-07-05 | Sterling Winthrop Inc. | Formulations for nanoparticulate x-ray blood pool contrast agents using high molecular weight nonionic surfactants |
| US5401492A (en) | 1992-12-17 | 1995-03-28 | Sterling Winthrop, Inc. | Water insoluble non-magnetic manganese particles as magnetic resonance contract enhancement agents |
| US5654006A (en) | 1993-02-12 | 1997-08-05 | Mayo Foundation For Medical Education And Research | Condensed-phase microparticle composition and method |
| US5820879A (en) | 1993-02-12 | 1998-10-13 | Access Pharmaceuticals, Inc. | Method of delivering a lipid-coated condensed-phase microparticle composition |
| US5753261A (en) | 1993-02-12 | 1998-05-19 | Access Pharmaceuticals, Inc. | Lipid-coated condensed-phase microparticle composition |
| US5264610A (en) | 1993-03-29 | 1993-11-23 | Sterling Winthrop Inc. | Iodinated aromatic propanedioates |
| US5436011A (en) | 1993-04-16 | 1995-07-25 | Bristol-Myers Squibb Company | Solid pharmaceutical dosage form and a method for reducing abrasion |
| DK0621032T3 (da) | 1993-04-23 | 2000-10-23 | Novartis Ag | Lægemiddelform med reguleret afgivelse |
| US5886026A (en) | 1993-07-19 | 1999-03-23 | Angiotech Pharmaceuticals Inc. | Anti-angiogenic compositions and methods of use |
| ES2068762B1 (es) * | 1993-07-21 | 1995-12-01 | Lipotec Sa | Un nuevo preparado farmaceutico para mejorar la biodisponibilidad de drogas de dificil absorcion y procedimiento para su obtencion. |
| US5362442A (en) | 1993-07-22 | 1994-11-08 | 2920913 Canada Inc. | Method for sterilizing products with gamma radiation |
| CA2128821A1 (en) | 1993-07-27 | 1995-01-28 | Dilip J. Gole | Freeze-dried pharmaceutical dosage form and process for separation thereof |
| JP2916978B2 (ja) * | 1993-08-25 | 1999-07-05 | エスエス製薬株式会社 | 放出開始制御型製剤 |
| US5380790A (en) | 1993-09-09 | 1995-01-10 | Eastman Chemical Company | Process for the preparation of acrylic polymers for pharmaceutical coatings |
| GB9319568D0 (en) * | 1993-09-22 | 1993-11-10 | Euro Celtique Sa | Pharmaceutical compositions and usages |
| US6123900A (en) | 1993-10-28 | 2000-09-26 | Vellutato; Arthur L. | Method of sterilization |
| US5484608A (en) | 1994-03-28 | 1996-01-16 | Pharmavene, Inc. | Sustained-release drug delivery system |
| US5411745A (en) | 1994-05-25 | 1995-05-02 | Euro-Celtique, S.A. | Powder-layered morphine sulfate formulations |
| TW384224B (en) | 1994-05-25 | 2000-03-11 | Nano Sys Llc | Method of preparing submicron particles of a therapeutic or diagnostic agent |
| US5718388A (en) | 1994-05-25 | 1998-02-17 | Eastman Kodak | Continuous method of grinding pharmaceutical substances |
| US5958458A (en) | 1994-06-15 | 1999-09-28 | Dumex-Alpharma A/S | Pharmaceutical multiple unit particulate formulation in the form of coated cores |
| US5525328A (en) | 1994-06-24 | 1996-06-11 | Nanosystems L.L.C. | Nanoparticulate diagnostic diatrizoxy ester X-ray contrast agents for blood pool and lymphatic system imaging |
| US5587143A (en) | 1994-06-28 | 1996-12-24 | Nanosystems L.L.C. | Butylene oxide-ethylene oxide block copolymer surfactants as stabilizer coatings for nanoparticle compositions |
| JPH08175977A (ja) * | 1994-09-16 | 1996-07-09 | Euro Celtique Sa | アクリル系ポリマーの水性分散液で被覆した放出制御型製剤及びその製法 |
| US6117455A (en) * | 1994-09-30 | 2000-09-12 | Takeda Chemical Industries, Ltd. | Sustained-release microcapsule of amorphous water-soluble pharmaceutical active agent |
| JPH08137062A (ja) * | 1994-11-07 | 1996-05-31 | Konica Corp | ハロゲン化銀写真感光材料用定着液及び該定着液を用いた処理方法 |
| JPH08157392A (ja) * | 1994-12-01 | 1996-06-18 | Kanegafuchi Chem Ind Co Ltd | 放出制御型製剤 |
| US5872104A (en) | 1994-12-27 | 1999-02-16 | Oridigm Corporation | Combinations and methods for reducing antimicrobial resistance |
| US5585108A (en) | 1994-12-30 | 1996-12-17 | Nanosystems L.L.C. | Formulations of oral gastrointestinal therapeutic agents in combination with pharmaceutically acceptable clays |
| US5628981A (en) | 1994-12-30 | 1997-05-13 | Nano Systems L.L.C. | Formulations of oral gastrointestinal diagnostic x-ray contrast agents and oral gastrointestinal therapeutic agents |
| US5466440A (en) | 1994-12-30 | 1995-11-14 | Eastman Kodak Company | Formulations of oral gastrointestinal diagnostic X-ray contrast agents in combination with pharmaceutically acceptable clays |
| US5834024A (en) * | 1995-01-05 | 1998-11-10 | Fh Faulding & Co. Limited | Controlled absorption diltiazem pharmaceutical formulation |
| US5616707A (en) * | 1995-01-06 | 1997-04-01 | Crooks; Peter A. | Compounds which are useful for prevention and treatment of central nervous system disorders |
| US5560932A (en) | 1995-01-10 | 1996-10-01 | Nano Systems L.L.C. | Microprecipitation of nanoparticulate pharmaceutical agents |
| US5662883A (en) | 1995-01-10 | 1997-09-02 | Nanosystems L.L.C. | Microprecipitation of micro-nanoparticulate pharmaceutical agents |
| US5665331A (en) | 1995-01-10 | 1997-09-09 | Nanosystems L.L.C. | Co-microprecipitation of nanoparticulate pharmaceutical agents with crystal growth modifiers |
| US5569448A (en) | 1995-01-24 | 1996-10-29 | Nano Systems L.L.C. | Sulfated nonionic block copolymer surfactants as stabilizer coatings for nanoparticle compositions |
| US5571536A (en) | 1995-02-06 | 1996-11-05 | Nano Systems L.L.C. | Formulations of compounds as nanoparticulate dispersions in digestible oils or fatty acids |
| US5560931A (en) | 1995-02-14 | 1996-10-01 | Nawosystems L.L.C. | Formulations of compounds as nanoparticulate dispersions in digestible oils or fatty acids |
| US5534270A (en) | 1995-02-09 | 1996-07-09 | Nanosystems Llc | Method of preparing stable drug nanoparticles |
| US5593657A (en) | 1995-02-09 | 1997-01-14 | Nanosystems L.L.C. | Barium salt formulations stabilized by non-ionic and anionic stabilizers |
| US5518738A (en) | 1995-02-09 | 1996-05-21 | Nanosystem L.L.C. | Nanoparticulate nsaid compositions |
| US5622938A (en) | 1995-02-09 | 1997-04-22 | Nano Systems L.L.C. | Sugar base surfactant for nanocrystals |
| US5591456A (en) | 1995-02-10 | 1997-01-07 | Nanosystems L.L.C. | Milled naproxen with hydroxypropyl cellulose as a dispersion stabilizer |
| US5500204A (en) | 1995-02-10 | 1996-03-19 | Eastman Kodak Company | Nanoparticulate diagnostic dimers as x-ray contrast agents for blood pool and lymphatic system imaging |
| US5573783A (en) * | 1995-02-13 | 1996-11-12 | Nano Systems L.L.C. | Redispersible nanoparticulate film matrices with protective overcoats |
| US5510118A (en) | 1995-02-14 | 1996-04-23 | Nanosystems Llc | Process for preparing therapeutic compositions containing nanoparticles |
| US5543133A (en) | 1995-02-14 | 1996-08-06 | Nanosystems L.L.C. | Process of preparing x-ray contrast compositions containing nanoparticles |
| US5580579A (en) | 1995-02-15 | 1996-12-03 | Nano Systems L.L.C. | Site-specific adhesion within the GI tract using nanoparticles stabilized by high molecular weight, linear poly (ethylene oxide) polymers |
| US5534263A (en) | 1995-02-24 | 1996-07-09 | Alza Corporation | Active agent dosage form comprising a matrix and at least two insoluble bands |
| JP4484247B2 (ja) | 1995-02-24 | 2010-06-16 | エラン ファーマ インターナショナル，リミティド | ナノ粒子分散体を含有するエアロゾル |
| US5718919A (en) | 1995-02-24 | 1998-02-17 | Nanosystems L.L.C. | Nanoparticles containing the R(-)enantiomer of ibuprofen |
| US5747001A (en) | 1995-02-24 | 1998-05-05 | Nanosystems, L.L.C. | Aerosols containing beclomethazone nanoparticle dispersions |
| US5565188A (en) | 1995-02-24 | 1996-10-15 | Nanosystems L.L.C. | Polyalkylene block copolymers as surface modifiers for nanoparticles |
| US5643552A (en) | 1995-03-09 | 1997-07-01 | Nanosystems L.L.C. | Nanoparticulate diagnostic mixed carbonic anhydrides as x-ray contrast agents for blood pool and lymphatic system imaging |
| US5472683A (en) | 1995-03-09 | 1995-12-05 | Eastman Kodak Company | Nanoparticulate diagnostic mixed carbamic anhydrides as X-ray contrast agents for blood pool and lymphatic system imaging |
| US5573749A (en) | 1995-03-09 | 1996-11-12 | Nano Systems L.L.C. | Nanoparticulate diagnostic mixed carboxylic anhydrides as X-ray contrast agents for blood pool and lymphatic system imaging |
| US5567441A (en) | 1995-03-24 | 1996-10-22 | Andrx Pharmaceuticals Inc. | Diltiazem controlled release formulation |
| US5521218A (en) | 1995-05-15 | 1996-05-28 | Nanosystems L.L.C. | Nanoparticulate iodipamide derivatives for use as x-ray contrast agents |
| US5573750A (en) | 1995-05-22 | 1996-11-12 | Nanosystems L.L.C. | Diagnostic imaging x-ray contrast agents |
| AU702801B2 (en) | 1995-07-14 | 1999-03-04 | Darwin Discovery Limited | Therapeutic use of D-threo-methylphenidate |
| GB9514451D0 (en) | 1995-07-14 | 1995-09-13 | Chiroscience Ltd | Sustained-release formulation |
| DE19526759A1 (de) * | 1995-07-21 | 1997-01-23 | Wacker Chemie Gmbh | Redispergierbare, vernetzbare Dispersionspulver |
| DE19529445A1 (de) | 1995-08-10 | 1997-02-13 | Basf Ag | Verwendung von Polymerisaten auf Basis von Ethylen, (Meth)acrylsäureestern und (Meth)acrylsäure zum Beschichten oder Versiegeln von Verbundsicherheitsglasscheiben |
| AR004014A1 (es) * | 1995-10-13 | 1998-09-30 | Meiji Seika Kaisha | Una composicion antibacteriana de cefditoren pivoxilo para administracion oral y metodo para obtener dicha composicion |
| US5807579A (en) | 1995-11-16 | 1998-09-15 | F.H. Faulding & Co. Limited | Pseudoephedrine combination pharmaceutical compositions |
| US5908850A (en) * | 1995-12-04 | 1999-06-01 | Celgene Corporation | Method of treating attention deficit disorders with d-threo methylphenidate |
| US6355656B1 (en) * | 1995-12-04 | 2002-03-12 | Celgene Corporation | Phenidate drug formulations having diminished abuse potential |
| US5837284A (en) * | 1995-12-04 | 1998-11-17 | Mehta; Atul M. | Delivery of multiple doses of medications |
| SE9600046D0 (sv) | 1996-01-05 | 1996-01-05 | Astra Ab | New pharmaceutical formulation |
| US5840332A (en) | 1996-01-18 | 1998-11-24 | Perio Products Ltd. | Gastrointestinal drug delivery system |
| ES2200158T3 (es) * | 1996-03-08 | 2004-03-01 | Nycomed Danmark Aps | Cmpuesto de dosificacion de unidades multiples, de liberacion modificada. |
| US5766623A (en) * | 1996-03-25 | 1998-06-16 | State Of Oregon Acting By And Through The Oregon State Board Of Higher Education On Behalf Of Oregon State University | Compactable self-sealing drug delivery agents |
| CN101518517B (zh) | 1996-08-16 | 2014-11-26 | 阿尔萨公司 | 药物剂量逐渐增加的剂型 |
| HRP970493A2 (en) * | 1996-09-23 | 1998-08-31 | Wienman E. Phlips | Oral delayed immediate release medical formulation and method for preparing the same |
| PT932388E (pt) | 1996-09-30 | 2006-07-31 | Alza Corp | Forma de dosagem e metodo para administracao de farmacos |
| FR2754710B1 (fr) * | 1996-10-22 | 1998-12-31 | Prographarm Lab | Procede de preparation d'une forme pharmaceutique multiparticulaire a liberation controlee plurisequentielle |
| US6495579B1 (en) * | 1996-12-02 | 2002-12-17 | Angiotech Pharmaceuticals, Inc. | Method for treating multiple sclerosis |
| DE19653631A1 (de) | 1996-12-20 | 1998-06-25 | Basf Coatings Ag | Verfahren zum Herstellen von durch Strahlung vernetzbaren polymeren Acryl- oder Methacrylsäureestern |
| CA2275604A1 (en) * | 1997-01-03 | 1998-07-09 | Kenneth Iain Cumming | Sustained release cisapride mini-tablet formulation |
| US5776856A (en) | 1997-02-04 | 1998-07-07 | Isp Investments Inc. | Soluble polymer based matrix for chemically active water insoluble components |
| US6045829A (en) | 1997-02-13 | 2000-04-04 | Elan Pharma International Limited | Nanocrystalline formulations of human immunodeficiency virus (HIV) protease inhibitors using cellulosic surface stabilizers |
| WO1998035666A1 (en) | 1997-02-13 | 1998-08-20 | Nanosystems Llc | Formulations of nanoparticle naproxen tablets |
| US5840329A (en) | 1997-05-15 | 1998-11-24 | Bioadvances Llc | Pulsatile drug delivery system |
| BR9809895A (pt) | 1997-07-01 | 2000-08-01 | Pfizer Prod Inc | Formas de dosagem da sertralina de liberação retardada |
| GB9714675D0 (en) | 1997-07-11 | 1997-09-17 | Smithkline Beecham Plc | Novel composition |
| US5885616A (en) | 1997-08-18 | 1999-03-23 | Impax Pharmaceuticals, Inc. | Sustained release drug delivery system suitable for oral administration |
| US6440455B1 (en) | 1997-09-02 | 2002-08-27 | Children's Medical Center Corporation | Methods for modulating the axonal outgrowth of central nervous system neurons |
| WO1999012524A1 (en) * | 1997-09-11 | 1999-03-18 | Nycomed Danmark A/S | MODIFIED RELEASE MULTIPLE-UNITS COMPOSITIONS OF NON-STEROID ANTI-INFLAMMATORY DRUG SUBSTANCES (NSAIDs) |
| ES2159965T3 (es) | 1997-09-26 | 2001-10-16 | Wacker Chemie Gmbh | Proceso para la preparacion de polimeros estabilizados con coloides protectores. |
| US6327254B1 (en) | 1997-10-14 | 2001-12-04 | Lucent Technologies Inc. | Method for bandwidth sharing in a multiple access system for communications networks |
| AU1827799A (en) * | 1997-12-15 | 1999-07-05 | Axia Therapeutics, Inc. | Oral delivery formulation |
| US6123923A (en) | 1997-12-18 | 2000-09-26 | Imarx Pharmaceutical Corp. | Optoacoustic contrast agents and methods for their use |
| US6066292A (en) | 1997-12-19 | 2000-05-23 | Bayer Corporation | Sterilization process for pharmaceutical suspensions |
| US6004584A (en) | 1998-03-02 | 1999-12-21 | The Procter & Gamble Company | Highly absorbent body powders |
| US6372254B1 (en) | 1998-04-02 | 2002-04-16 | Impax Pharmaceuticals Inc. | Press coated, pulsatile drug delivery system suitable for oral administration |
| US6156342A (en) | 1998-05-26 | 2000-12-05 | Andex Pharmaceuticals, Inc. | Controlled release oral dosage form |
| ATE277594T1 (de) * | 1998-06-03 | 2004-10-15 | Alza Corp | Vorrichtungen um eine verlängerte medikamententherapie zu erreichen |
| US6153225A (en) | 1998-08-13 | 2000-11-28 | Elan Pharma International Limited | Injectable formulations of nanoparticulate naproxen |
| US6165506A (en) | 1998-09-04 | 2000-12-26 | Elan Pharma International Ltd. | Solid dose form of nanoparticulate naproxen |
| US8293277B2 (en) | 1998-10-01 | 2012-10-23 | Alkermes Pharma Ireland Limited | Controlled-release nanoparticulate compositions |
| US6322819B1 (en) | 1998-10-21 | 2001-11-27 | Shire Laboratories, Inc. | Oral pulsed dose drug delivery system |
| UA67802C2 (uk) | 1998-10-23 | 2004-07-15 | Пфайзер Рісьоч Енд Дівелепмент Компані, Н.В./С.А. | Фармацевтична композиція з контрольованим вивільненням інгібітора цгмф фде-5 (варіанти), спосіб її одержання та спосіб лікування еректильної дисфункції |
| CN100444830C (zh) * | 1998-11-02 | 2008-12-24 | 伊兰公司，Plc | 多颗粒改进释放组合物 |
| IT1303692B1 (it) | 1998-11-03 | 2001-02-23 | Chiesi Farma Spa | Procedimento per la preparazione di sospensioni di particelle difarmaci da somministrare per inalazione. |
| US6428814B1 (en) | 1999-10-08 | 2002-08-06 | Elan Pharma International Ltd. | Bioadhesive nanoparticulate compositions having cationic surface stabilizers |
| US6375986B1 (en) | 2000-09-21 | 2002-04-23 | Elan Pharma International Ltd. | Solid dose nanoparticulate compositions comprising a synergistic combination of a polymeric surface stabilizer and dioctyl sodium sulfosuccinate |
| DK1140012T3 (da) * | 1998-12-17 | 2004-07-12 | Alza Corp | Omdannelse af væskefyldte gelatinekapsler til systemer til kontrolleret frigivelsessystemer ved flere coatinger |
| US6419960B1 (en) * | 1998-12-17 | 2002-07-16 | Euro-Celtique S.A. | Controlled release formulations having rapid onset and rapid decline of effective plasma drug concentrations |
| US6524528B1 (en) | 1999-03-02 | 2003-02-25 | Suzanne C. Gottuso | Method of sterilizing a tattooing solution through irradiation |
| US6270806B1 (en) | 1999-03-03 | 2001-08-07 | Elan Pharma International Limited | Use of peg-derivatized lipids as surface stabilizers for nanoparticulate compositions |
| US6267989B1 (en) | 1999-03-08 | 2001-07-31 | Klan Pharma International Ltd. | Methods for preventing crystal growth and particle aggregation in nanoparticulate compositions |
| US6025502A (en) | 1999-03-19 | 2000-02-15 | The Trustees Of The University Of Pennsylvania | Enantopselective synthesis of methyl phenidate |
| EP1191924A4 (en) | 1999-04-06 | 2005-02-09 | Pharmaquest Ltd | PHARMACEUTICAL DOSAGE FORM FOR INTERMITTENT ADMINISTRATION OF (D-THREO) -METHYLPHENIDATE AND A SECOND STIMULANT OF THE CENTRAL NERVOUS SYSTEM |
| ATE271922T1 (de) | 1999-06-01 | 2004-08-15 | Elan Pharma Int Ltd | Kleinmühle und verfahren dafür |
| US6596230B1 (en) | 2000-01-28 | 2003-07-22 | Baxter International Inc. | Device and method for pathogen inactivation of therapeutic fluids with sterilizing radiation |
| US6627223B2 (en) | 2000-02-11 | 2003-09-30 | Eurand Pharmaceuticals Ltd. | Timed pulsatile drug delivery systems |
| US6458384B2 (en) * | 2000-02-23 | 2002-10-01 | Impetus Ag | Pharmaceutical with predetermined activity profile |
| JP2001316294A (ja) | 2000-03-14 | 2001-11-13 | Pfizer Prod Inc | ｏ−バニリンおよびｏ−バニリン／テトラメチルクロマニルカルボン酸化合物の組み合わせの使用法 |
| CN1427729A (zh) | 2000-03-23 | 2003-07-02 | 科利昂特有限公司 | 生物材料消毒方法 |
| GB0009773D0 (en) | 2000-04-19 | 2000-06-07 | Univ Cardiff | Particulate composition |
| WO2001085344A1 (en) | 2000-04-26 | 2001-11-15 | Elan Pharma International, Ltd. | Apparatus for sanitary wet milling |
| US6316029B1 (en) | 2000-05-18 | 2001-11-13 | Flak Pharma International, Ltd. | Rapidly disintegrating solid oral dosage form |
| GB0018528D0 (en) | 2000-07-27 | 2000-09-13 | Photocure Asa | Compounds |
| US20030219461A1 (en) | 2000-09-12 | 2003-11-27 | Britten Nancy J. | Parenteral combination therapy for infective conditions |
| US6482440B2 (en) * | 2000-09-21 | 2002-11-19 | Phase 2 Discovery, Inc. | Long acting antidepressant microparticles |
| US6344215B1 (en) | 2000-10-27 | 2002-02-05 | Eurand America, Inc. | Methylphenidate modified release formulations |
| ES2280582T3 (es) | 2001-09-19 | 2007-09-16 | Elan Pharma International Limited | Formulaciones de insulina en nanoparticulas. |
| CA2475092C (en) | 2002-02-04 | 2012-05-01 | Christian F. Wertz | Nanoparticulate compositions having lysozyme as a surface stabilizer |
| WO2004019901A2 (en) * | 2002-08-30 | 2004-03-11 | Orchid Chemicals & Pharmaceuticals Ltd. | Sustained release pharmaceutical composition |
| EP1553927B9 (en) | 2002-09-11 | 2011-09-21 | Elan Pharma International Limited | Gel-stabilized nanoparticulate active agent compositions |
| US7220431B2 (en) * | 2002-11-27 | 2007-05-22 | Regents Of The University Of Minnesota | Methods and compositions for applying pharmacologic agents to the ear |
| US8512727B2 (en) | 2003-03-03 | 2013-08-20 | Alkermes Pharma Ireland Limited | Nanoparticulate meloxicam formulations |
| US7749533B2 (en) * | 2003-05-07 | 2010-07-06 | Akina, Inc. | Highly plastic granules for making fast melting tablets |
| DE602004018150D1 (de) | 2003-08-08 | 2009-01-15 | Elan Pharma Int Ltd | Neue metaxalon-zusammensetzungen |
| US7494950B2 (en) * | 2003-09-05 | 2009-02-24 | Synthes (U.S.A.) | Bone cement compositions having fiber-reinforcement and/or increased flowability |
| US8153159B2 (en) * | 2003-09-18 | 2012-04-10 | Cephalon, Inc. | Modafinil modified release pharmaceutical compositions |
| WO2005112970A2 (en) * | 2004-05-12 | 2005-12-01 | The Brigham And Women's Hospital, Inc. | Use of gelsolin to treat infections |
| US7754230B2 (en) * | 2004-05-19 | 2010-07-13 | The Regents Of The University Of California | Methods and related compositions for reduction of fat |
| US20060127468A1 (en) * | 2004-05-19 | 2006-06-15 | Kolodney Michael S | Methods and related compositions for reduction of fat and skin tightening |
| AU2006336417A1 (en) | 2005-05-10 | 2007-08-02 | Elan Pharma International, Limited | Nanoparticulate clopidogrel formulations |
| JP2008543843A (ja) | 2005-06-13 | 2008-12-04 | エラン ファーマ インターナショナル リミテッド | ナノ粒子クロピドグレル及びアスピリンの配合製剤 |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5445829A (en) * | 1989-05-05 | 1995-08-29 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
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| CN100444830C (zh) | 多颗粒改进释放组合物 | |
| AU2012202743B2 (en) | Multiparticulate modified release composition | |
| AU2007203497B2 (en) | Multiparticulate modified release composition |
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