[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

CN1403076A - 多颗粒改进释放组合物 - Google Patents

多颗粒改进释放组合物 Download PDF

Info

Publication number
CN1403076A
CN1403076A CN02132215A CN02132215A CN1403076A CN 1403076 A CN1403076 A CN 1403076A CN 02132215 A CN02132215 A CN 02132215A CN 02132215 A CN02132215 A CN 02132215A CN 1403076 A CN1403076 A CN 1403076A
Authority
CN
China
Prior art keywords
active component
composition
modified release
multiparticulate modified
release composition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN02132215A
Other languages
English (en)
Inventor
J·G·德瓦尼
N·M·M·梵宁
P·斯塔克
G·S·雷克希
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Elan Pharma International Ltd
Original Assignee
Elan Company PLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22312931&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CN1403076(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Elan Company PLC filed Critical Elan Company PLC
Publication of CN1403076A publication Critical patent/CN1403076A/zh
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4458—Non condensed piperidines, e.g. piperocaine only substituted in position 2, e.g. methylphenidate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Communicable Diseases (AREA)
  • Psychiatry (AREA)
  • Pulmonology (AREA)
  • Oncology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

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

多颗粒改进释放组合物
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。
WO98/14168(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，WO98/14168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EP0274734(Pharmi dea 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。
US5,158,777(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。
US4,728,512、US4,794,001和US4,904,476(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EudragitRS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。
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。
       表1：即时释放成分溶液
组分盐酸哌醋甲酯聚乙二醇6000聚乙烯吡咯烷酮纯水    量％(w/w)
(i)       (ii)13.0      13.00.5       0.53.583.5      86.5
(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。
          表2：改进释放成分包衣溶液组分                                    量％(w/w)
        (i)    (ii)    (iii)    (iv)    (v)   (vi)   (vii)  (viii)Eudragit 49.7   42.0    47.1     53.2    40.6   -      -      25.0RS12.5Eudragit -      -       -        -              54.35  46.5   -S12.5Eudragit -      -       -        -       -      -      -      25.0L12.5聚乙烯吡    -      -       -        0.35    0.3    -      -      -咯烷酮邻苯二甲    0.5    0.5     0.6      1.35    0.6    1.3    1.1    -酸二乙酯柠檬酸三    -      -       -        -       -      -      -      1.25乙酯异丙醇      39.8   33.1    37.2     45.1    33.8   44.35  49.6   46.5丙酮        10.0   8.3     9.3      -       8.4    -      -      -滑石1       -      16.0    5.9      -       16.3   -      2.8    2.25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USP1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USP1型设备(100rpm)按照美国药典修改版的肠溶保护法(USP23，1995，1795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pH6.8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。
     表3(a)：用表2中给出的包衣溶液配制的改进释放成分的溶解数据
包衣层配方 (i)   (i)   (i)    (ii)    (ii)    (ii)    (iii)  (iii)
包衣层含量(％所得重量) 4％   6％   10％   4％     6％     8％     4％     6％
时间(小时) 活性组分释放的％
1246810 0     0     0      8.5     1.3     1.4     6.1     3.017.0  3.3   0      36.9    7.1     3.7     21.3    8.251.5  22.1  0      80.0    40.3    15.1    62.3    26.375.8  46.5  0      92.8    72.4    31.2    82.1    52.686.0  65.5  10.2   97.5    83.0    47.5    91.3    73.091.3  76.5  17.3   -       -       -       97.7    86.5
(符号“-”表示未给出测定值)
表3(b)：用表2中给出的包衣溶液配制的改进释放成分的溶解数据
包衣层配方 (iv)    (iv)   (iv)    (v)    (v)
包衣层含量(％重量增加) 10％    15％   20％    10％   12.5％
时间(小时) 活性组分释放的％
1246810 3.5     0.9    1.1     1.3    1.013.4    5.4    2.9     6.1    2.947.1    22.5   13.8    42.4   21.280.0    52.0   36.9    77.5   54.494.8    70.3   61.0    92.4   79.7103     81.5   76.1    -      -
(符号“-”表示未给出测定值)
表3(c)：用表2中给出的包衣溶液配制的改进释放成分的溶解数据
包衣层配方 (vi)   (vi)  (vi)    (vi)*  (vii)  (vii)   (viii)  (viii)
包衣层含量(％所得重量) 5％    10％   15％   15％   15％     20％    20％   30％
时间(小时) 活性组分释放的％
1246810 33.2   0.4    0       0      3.9     0.6     3.8    2.180.6   9.8    0       0.5    52.0    12.4    7.4    3.192.2   43.5   10.1    44.0   85.0    61.6    43.7   8.993.9   61.6   29.9    80.2   89.9    75.3    72.4   39.694.3   67.5   48.4    69.0   91.4    79.6    79.2   63.994.4   -      60.0    -      -       -       79.5   73.4
(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.含有IR成分和改进释放成分的组合物的溶解数据
MR包衣制剂 (vii)    (viii)
包衣层含量(重量增加％) 30％     30％
0 0        0
0.5 49.7     50.2
1 49.7     50.5
2 49.8     51.1
4 56.1     54.1
6 65.2     68.0
8 72.2     81.8
10 76.6     87.0
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。                                                 
     表5(a)：用100mg改进释放(MR)成分给100mg
         IR成分包囊而得到20mg剂量浓度的产品
IR成分          ％(w/w)盐酸哌醋甲酯    10微晶纤维素      40乳糖            45聚维酮          5 MR成分        ％(w/w)盐酸哌醋甲酯  10微晶纤维素    40EudragitRS 45聚维酮        5
 表5(b)：用50mg改进释放(MR)成分给50mg
  IR成分包囊而得到20mg剂量浓度的产品
IR成分        ％(w/w)盐酸哌醋甲酯  20微晶纤维素    50乳糖          28聚维酮        2 MR成分       ％(w/w)盐酸哌醋甲酯 20微晶纤维素   50EudragitS 28聚维酮       5
(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RitalinIR4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 (36)

1.一种多颗粒改进释放组合物，它含有至少一种活性组分并具有包括含第一部分活性组分颗粒群的第一种成分和至少一种后续成分，各后续成分包括含活性组分的后续颗粒群，第一种成分和后续成分中包含的活性组分相同或不同；其中至少一种活性组分的后续颗粒群进一步包括改进释放包衣层或另一方面或另外的改进释放基质物质，使得在对受试者口服转运后该组合物以一种搏动方式释放活性组分或多种活性组分。
2.根据权利要求1所述的多颗粒改进释放组合物，其中所述组合物包括第一种成分和一种后续成分。
3.根据权利要求2所述的多颗粒改进释放组合物，其中所述的第一种成分包括一种即时释放组分且后续成分是一种改进释放成分。
4.根据权利要求3所述的多颗粒改进释放组合物，其中所述的改进释放成分包括具有改进释放包衣层的颗粒。
5.根据权利要求3所述的多颗粒改进释放组合物，其中所述的改进释放成分包括改进释放基质物质。
6.根据权利要求1所述的多颗粒改进释放组合物，其中所述的第一部分含活性组分的颗粒群和至少一种含活性组分的后续颗粒群包括相同的活性组分。
7.根据权利要求1所述的多颗粒改进释放组合物，其中所述的第一部分含活性组分的颗粒群含有两种或多种活性组分。
8.根据权利要求1所述的多颗粒改进释放组合物，其中所述的至少一种含活性组分的后续颗粒群含有两种或多种活性组分。
9.根据权利要求1所述的多颗粒改进释放组合物，其中所述的活性组分基本上包括一种光学纯的对映体或对映体的混合物、外消旋物或其它形式。
10.根据权利要求1所述的多颗粒改进释放组合物，其中所述第一种成分和后续成分中的至少一种进一步包括一种促进剂。
11.根据权利要求1所述的多颗粒改进释放组合物，其中所述第一种成分和后续成分中包含的活性组分的量相同或不同。
12.根据权利要求11所述的多颗粒改进释放组合物，其中所述各成分中包含的活性组分的量约为0.1mg-约1g。
13.根据权利要求6所述的多颗粒改进释放组合物，其中所述的活性组分是哌醋甲酯或其药物上可接受的盐、其对映体或对映体的混合物或这些物质的混合物。
14.根据权利要求1所述的多颗粒改进释放组合物，其中所述的第一部分和后续的含活性组分的颗粒群在体外具有不同的溶解分布。
15.根据权利要求1所述的多颗粒改进释放组合物，其中所述的第一种成分是一种即时释放成分且至少一种后续成分是一种改进释放成分。
16.根据权利要求15所述的多颗粒改进释放组合物，在起作用过程中，它可在从含活性组分的后续颗粒群中释放活性组分前基本上从第一部分含活性组分的颗粒群中释放所有的活性组分。
17.根据权利要求1所述的多颗粒改进释放组合物，其中活性组分在受试者中的体内释放类似于以两种或多种剂量即时释放形式活性组分的形式给予相同活性组分的体内释放。
18.根据权利要求13所述的多颗粒改进释放组合物，其中活性组分在受试者中的体内释放类似于以两种或多种剂量即时释放形式活性组分的形式给予相同活性组分的体内释放。
19.根据权利要求16所述的多颗粒改进释放组合物，其中在体外水介质中的溶解分布方式使得在第一部分含活性组分的颗粒群中包含的约50％-100％的活性组分在给予该组合物的4小时内被释放出来；且在含活性组分的后续颗粒群中包含的约30％-100％的活性组分在给予该组合物的4-8小时内被释放出来。
20.根据权利要求19所述的多颗粒改进释放组合物，其中在体外水介质中的溶解分布方式使得在第一部分含活性组分的颗粒群中包含的约80％-100％的活性组分在给予该组合物的4小时内被释放出来且在含活性组分的后续颗粒群中包含的约60％-100％的活性组分在给予该组合物的4-8小时内被释放出来。
21.一种包括权利要求1的多颗粒改进释放组合物的固体口服剂型。
22.根据权利要求21所述的固体口服剂型，它包括填入硬胶囊或软胶囊中的第一部分和后续的含活性组分的颗粒的掺合物。
23.根据权利要求21所述的固体口服剂型，其中将第一种成分和后续成分分别和独立地压制成微片并填入硬胶囊或软胶囊。
24.根据权利要求2 1所述的固体口服剂型，其中将所述的第一种成分压制成多层片的第一层并将至少一种后续成分压制成多层片的后续层。
25.根据权利要求21所述的固体口服剂型，其中将第一种成分和后续成分制成快速溶解的剂型。
26.根据权利要求25所述的固体口服剂型，其中所述的快速溶解剂型是速溶片剂型。
27.权利要求1的多颗粒改进释放组合物在制备用于治疗以患者对该组合物中包含的至少一种活性组分产生耐药性为特征的疾病的药剂中的用途。
28.权利要求1的多颗粒改进释放组合物在制备用于治疗注意力不集中疾病的药物中的用途。
29.权利要求13的多颗粒改进释放组合物在制备用于治疗注意力不集中疾病的药物中的用途。
30.一种治疗以患者对治疗疾病过程中给予的活性组分产生耐药性为特征的疾病的方法，该方法包括给予治疗有效量的权利要求1的多颗粒改进释放组合物的步骤。
31.一种治疗注意力不集中疾病的方法，该方法包括给予治疗有效量的权利要求1的多颗粒改进释放组合物的步骤。
32.一种治疗注意力不集中疾病的方法，该方法包括给予治疗有效量的权利要求13的多颗粒改进释放组合物的步骤。
33.根据权利要求3所述的组合物，物质所述的改进释放成分包括一种pH依赖性聚合物，它在延缓时间后从改进释放成分中以脉冲方式释放活性组分。
34.根据权利要求33所述的组合物，其中所述的pH依赖性聚合物包衣层包括甲基丙烯酸酯共聚物。
35.根据权利要求33所述的组合物，其中所述的pH依赖性聚合物包衣层包括甲基丙烯酸酯和甲基丙烯酸铵共聚物的混合物，其含有量足以在延缓时间后实现从改进释放成分中以脉冲方式释放活性组分。
36.根据权利要求35所述的组合物，其中甲基丙烯酸酯与甲基丙烯酸铵共聚物的比例为1∶1。
CN02132215A 1998-11-02 2002-08-30 多颗粒改进释放组合物 Pending CN1403076A (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10672698P 1998-11-02 1998-11-02
US60/106,726 1998-11-02

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
CNB998140023A Division CN100444830C (zh) 1998-11-02 1999-11-01 多颗粒改进释放组合物

Publications (1)

Publication Number Publication Date
CN1403076A true CN1403076A (zh) 2003-03-19

Family

ID=22312931

Family Applications (2)

Application Number Title Priority Date Filing Date
CNB998140023A Expired - Lifetime CN100444830C (zh) 1998-11-02 1999-11-01 多颗粒改进释放组合物
CN02132215A Pending CN1403076A (zh) 1998-11-02 2002-08-30 多颗粒改进释放组合物

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CNB998140023A Expired - Lifetime CN100444830C (zh) 1998-11-02 1999-11-01 多颗粒改进释放组合物

Country Status (31)

Country Link
US (7) US6228398B1 (zh)
EP (3) EP1126826B3 (zh)
JP (2) JP4613275B2 (zh)
KR (3) KR100812832B1 (zh)
CN (2) CN100444830C (zh)
AR (1) AR021858A1 (zh)
AT (1) ATE411011T3 (zh)
AU (4) AU770645B2 (zh)
BR (1) BRPI9914977B8 (zh)
CA (2) CA2348871C (zh)
CO (1) CO5261536A1 (zh)
CY (1) CY1110421T1 (zh)
CZ (1) CZ303495B6 (zh)
DE (1) DE69939748D1 (zh)
DK (1) DK1126826T6 (zh)
ES (1) ES2313797T7 (zh)
HK (1) HK1050487A1 (zh)
HU (1) HU230454B1 (zh)
ID (1) ID29852A (zh)
IL (4) IL142896A0 (zh)
MX (1) MXPA01004381A (zh)
MY (1) MY122159A (zh)
NO (1) NO343240B1 (zh)
NZ (1) NZ511442A (zh)
PE (1) PE20001322A1 (zh)
PL (1) PL205109B1 (zh)
PT (1) PT1126826E (zh)
RU (1) RU2236847C2 (zh)
SK (1) SK287674B6 (zh)
TR (1) TR200101216T2 (zh)
WO (1) WO2000025752A1 (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101410094B (zh) * 2006-01-27 2013-04-17 阿普塔利斯制药股份有限公司 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
CN105025883A (zh) * 2013-03-29 2015-11-04 沃克哈特有限公司 右哌甲酯或其盐的调节释放的药物组合物

Families Citing this family (363)

* Cited by examiner, † Cited by third party
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
AU2004200325B2 (en) * 1998-10-21 2006-09-28 Shire Llc Oral Pulsed Dose Drug Delivery System
US6322819B1 (en) 1998-10-21 2001-11-27 Shire Laboratories, Inc. Oral pulsed dose drug delivery system
US20080102121A1 (en) * 1998-11-02 2008-05-01 Elan Pharma International Limited Compositions comprising nanoparticulate meloxicam and controlled release hydrocodone
WO2008030209A2 (en) * 2005-05-23 2008-03-13 Elan Pharma International Limited Nanoparticulate and controlled release compositions comprising a platelet aggregation inhibitor
US20090297602A1 (en) * 1998-11-02 2009-12-03 Devane John G Modified Release Loxoprofen Compositions
US20090149479A1 (en) * 1998-11-02 2009-06-11 Elan Pharma International Limited Dosing regimen
US20070122481A1 (en) * 1998-11-02 2007-05-31 Elan Corporation Plc Modified Release Compositions Comprising a Fluorocytidine Derivative for the Treatment of Cancer
US20080113025A1 (en) * 1998-11-02 2008-05-15 Elan Pharma International Limited Compositions comprising nanoparticulate naproxen and controlled release hydrocodone
US20060240105A1 (en) * 1998-11-02 2006-10-26 Elan Corporation, Plc Multiparticulate modified release composition
EP1126826B3 (en) * 1998-11-02 2019-05-15 Alkermes Pharma Ireland Limited Multiparticulate modified release composition of methylphenidate
US6673367B1 (en) 1998-12-17 2004-01-06 Euro-Celtique, S.A. Controlled/modified release oral methylphenidate formulations
US7083808B2 (en) 1998-12-17 2006-08-01 Euro-Celtique S.A. Controlled/modified release oral methylphenidate formulations
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
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
EP2295043A1 (en) 1999-10-29 2011-03-16 Euro-Celtique S.A. Controlled release hydrocodone formulations
US10179130B2 (en) 1999-10-29 2019-01-15 Purdue Pharma L.P. Controlled release hydrocodone formulations
US6500462B1 (en) * 1999-10-29 2002-12-31 Fmc Corporation Edible MCC/PGA coating composition
DK1248594T3 (da) 2000-01-19 2006-02-06 Mannkind Corp Formulering med multi-spidsfrigivelse til indgivelse af lægemidler
US6544555B2 (en) 2000-02-24 2003-04-08 Advancis Pharmaceutical Corp. Antibiotic product, use and formulation thereof
ES2272447T3 (es) * 2000-03-22 2007-05-01 The Secretary Of State For Defence Composicion farmaceutica para aplicar en superficies mucosas.
EP1280533A2 (en) * 2000-05-11 2003-02-05 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
JP2004507502A (ja) * 2000-08-30 2004-03-11 ファイザー・プロダクツ・インク 成長ホルモン分泌促進物質のための徐放性製剤
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
CN100518827C (zh) 2000-10-30 2009-07-29 欧罗赛铁克股份有限公司 控释氢可酮制剂
IT1319655B1 (it) 2000-11-15 2003-10-23 Eurand Int Microsfere di enzimi pancreatici con elevata stabilita' e relativometodo di preparazione.
WO2002043694A2 (en) * 2000-11-28 2002-06-06 Fmc Corporation Edible pga(propylene glycol alginate) 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
MXPA03008293A (es) * 2001-03-13 2003-12-11 Penwest Pharmaceuticals Co Formas de dosis cronoterapeuticas.
US20040115261A1 (en) * 2001-04-05 2004-06-17 Ashley Robert A. Controlled delivery of tetracycline compounds and tetracycline derivatives
US8329216B2 (en) * 2001-07-06 2012-12-11 Endo Pharmaceuticals Inc. Oxymorphone controlled release formulations
KR20030034171A (ko) * 2001-07-06 2003-05-01 엔도 파마슈티걸즈, 인크. 옥시모르폰 제어 방출 제형
WO2003005996A1 (en) * 2001-07-13 2003-01-23 Flow Focusing, Inc. Programmable controlled release injectable opioid formulation
US20060263401A1 (en) * 2001-07-13 2006-11-23 Flow Focusing, Inc. Formulation and Method for Preventing Infection
US20040142013A1 (en) * 2001-07-13 2004-07-22 Flow Focusing, Inc. Implantable orthopedic surgical devices with controlled release antimicrobial component
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
US20030055075A1 (en) * 2001-07-13 2003-03-20 Rubsamen Reid M. 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
US20150031718A1 (en) * 2001-08-06 2015-01-29 Purdue Pharma L.P. Pharmaceutical Formulation Containing Opioid Agonist, Opioid Antagonist and Gelling Agent
US20030157168A1 (en) 2001-08-06 2003-08-21 Christopher Breder Sequestered antagonist formulations
US20030068375A1 (en) 2001-08-06 2003-04-10 Curtis Wright Pharmaceutical formulation containing gelling agent
IL160222A0 (en) 2001-08-06 2004-07-25 Euro Celtique Sa Opioid agonist formulations with releasable and sequestered antagonist
JP2005523876A (ja) * 2001-09-26 2005-08-11 ペンウェスト ファーマシューティカルズ カンパニー 乱用の可能性が低減したオピオイド製剤
US9358214B2 (en) 2001-10-04 2016-06-07 Adare Pharmaceuticals, Inc. Timed, sustained release systems for propranolol
US8101209B2 (en) * 2001-10-09 2012-01-24 Flamel Technologies Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active principles
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
AUPR839001A0 (en) * 2001-10-19 2001-11-15 Eli Lilly And Company Dosage form, device and methods of treatment
US20060281797A1 (en) * 2001-12-11 2006-12-14 University Of Virginia Patent Foundation Neurorestoration with R(+) Pramipexole
AU2002360600B2 (en) * 2001-12-11 2007-11-29 University Of Virginia Patent Foundation Use of pramipexole to treat amyotrophic lateral sclerosis
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
JP2005527508A (ja) * 2002-03-07 2005-09-15 ヴェクトゥラ　リミテッド 経口デリバリー用急速溶融多粒子製剤
EP1492531B3 (fr) * 2002-04-09 2012-04-11 Flamel Technologies Formulation pharmaceutique orale sous forme de suspension aqueuse de microcapsules permettant la liberation modifiée d'amoxicilline
CN100553625C (zh) 2002-04-09 2009-10-28 弗拉梅技术公司 活性成分微囊的口服混悬液
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
AU2003296852A1 (en) * 2002-09-18 2004-05-04 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
JP2006507298A (ja) * 2002-10-30 2006-03-02 ファルマシア コーポレーション 経口持続放出型錠剤、ならびにその製造法および使用法
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
EP2218448B1 (en) 2002-12-13 2015-09-23 Durect Corporation Oral drug delivery system comprising high viscosity liquid carrier materials
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
MXPA05006954A (es) * 2002-12-26 2005-09-22 Pozen Inc Formas de dosificacion de capas multiples que contienen nsaids y triptanos.
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
US20040192781A1 (en) * 2003-03-31 2004-09-30 Haley Eugene T. Method of administration for metoclopramide and pharmaceutical formulation therefor
US20050137265A1 (en) * 2003-03-31 2005-06-23 Haley Eugene T. Rapidly dissolving metoclopramide solid oral dosage and method thereof
WO2004087175A1 (en) * 2003-04-04 2004-10-14 Pharmacia Corporation Oral extended release compressed tablets of multiparticulates
PL1615622T3 (pl) 2003-04-07 2012-12-31 Supernus Pharmaceuticals Inc Preparaty doksycyklin do jednorazowego dziennego podawania
WO2004100929A1 (en) 2003-05-12 2004-11-25 Synergia Pharma, Inc. Threo-dops controlled release formulation
US8158149B2 (en) * 2004-05-12 2012-04-17 Chelsea Therapeutics, Inc. Threo-DOPS controlled release formulation
WO2004112756A1 (en) 2003-06-26 2004-12-29 Isa Odidi Proton pump-inhibitor-containing capsules which comprise subunits differently structured for a delayed release of the active ingredient
EP1648418A4 (en) 2003-07-21 2011-11-16 Middlebrook Pharmaceuticals Inc ANTIBIOTIC PRODUCT, ITS USE AND FORMULATION
EP1648407A4 (en) 2003-07-21 2011-08-31 Middlebrook Pharmaceuticals Inc ANTIBIOTIC PRODUCT, CORRESPONDING USE AND FORMULATION
CA2533178C (en) 2003-07-21 2014-03-11 Advancis Pharmaceutical Corporation Antibiotic product, use and formulation thereof
JP2007502296A (ja) 2003-08-11 2007-02-08 アドバンシス ファーマスーティカル コーポレイション ロバストペレット
EP1653924A4 (en) 2003-08-12 2009-09-09 Middlebrook Pharmaceuticals In ANTIBIOTICS, USE AND FORMULATION ASSOCIATED
WO2005016317A1 (en) * 2003-08-19 2005-02-24 Themis Laboratories Private Limited Process for manufacture of extended release pellets containing diltiazem hci
EP1658034A4 (en) 2003-08-29 2011-06-22 Middlebrook Pharmaceuticals Inc ANTIBIOTIC PRODUCT, ITS USE AND FORMULATION
WO2005023217A2 (en) 2003-09-03 2005-03-17 Mallinckrodt Inc. Granular sustained release preparation and production thereof
WO2005027877A1 (en) 2003-09-15 2005-03-31 Advancis Pharmaceutical Corporation 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
EA200600598A1 (ru) * 2003-09-19 2006-08-25 Пенвест Фармасьютикалз Ко. Лекарственные формы замедленного высвобождения
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
US8007827B2 (en) * 2004-04-02 2011-08-30 Impax Laboratories, Inc. Pharmaceutical dosage forms having immediate release and/or controlled release properties
US20050239830A1 (en) * 2004-04-26 2005-10-27 Vikram Khetani Methods of diminishing co-abuse potential
CA2570916C (en) 2004-06-16 2013-06-11 Tap Pharmaceutical Products, Inc. Pulsed release dosage form of a ppi
US8394409B2 (en) * 2004-07-01 2013-03-12 Intellipharmaceutics Corp. Controlled extended drug release technology
AU2005269981A1 (en) 2004-07-02 2006-02-09 Bonck, John A Tablet for pulsed delivery
AU2005276554B2 (en) * 2004-08-23 2011-08-25 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
US9801982B2 (en) 2004-09-28 2017-10-31 Atrium Medical Corporation Implantable barrier device
US8312836B2 (en) 2004-09-28 2012-11-20 Atrium Medical Corporation Method and apparatus for application of a fresh coating on a medical device
US8367099B2 (en) 2004-09-28 2013-02-05 Atrium Medical Corporation Perforated fatty acid films
US8001922B2 (en) 2004-09-28 2011-08-23 Atrium Medical Corporation Application of a coating on a medical device
US9012506B2 (en) 2004-09-28 2015-04-21 Atrium Medical Corporation Cross-linked fatty acid-based biomaterials
EP1811933B1 (en) 2004-09-28 2016-03-23 Atrium Medical Corporation Barrier layer
US9000040B2 (en) 2004-09-28 2015-04-07 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
AU2005299490C1 (en) 2004-10-21 2012-01-19 Adare Pharmaceuticals, Inc. Taste-masked pharmaceutical compositions with gastrosoluble pore-formers
AR052225A1 (es) * 2004-11-04 2007-03-07 Astrazeneca Ab Formulaciones de tabletas de liberacion modificada par inhibidores de la bomba de protones
AR051654A1 (es) * 2004-11-04 2007-01-31 Astrazeneca Ab Nuevas formulaciones de pellets de liberacion modificada para inhibidores de la bomba de protones
US20060105038A1 (en) * 2004-11-12 2006-05-18 Eurand Pharmaceuticals Limited Taste-masked pharmaceutical compositions prepared by coacervation
CA2587710C (en) * 2004-11-16 2014-10-21 Elan Pharma International Ltd. Injectable nanoparticulate olanzapine formulations
US20060121112A1 (en) * 2004-12-08 2006-06-08 Elan Corporation, Plc Topiramate pharmaceutical composition
CA2591247A1 (en) * 2004-12-09 2006-06-15 Celgene Corporation Treatment of patients suffering from a disease having a family history or diagnosis of tics or tourette's syndrome with d-threo methylphenidate
CA2590675A1 (en) * 2004-12-15 2006-06-22 Elan Pharma International Ltd. Nanoparticulate tacrolimus formulations
US20060269596A1 (en) * 2005-01-12 2006-11-30 Gary Liversidge Controlled release compositions comprising an acylanilide
KR20070102563A (ko) * 2005-01-26 2007-10-18 엘란 파마 인터내셔널 리미티드 정신병치료제를 함유하는 조절방출형 조성물
GB0501809D0 (en) * 2005-01-28 2005-03-09 Pharmakodex Ltd Anti-migraine formulations
FR2884145A1 (fr) * 2005-04-06 2006-10-13 Flamel Technologies Sa Forme pharmaceutique orale de losartan
JP2008530185A (ja) * 2005-02-21 2008-08-07 フラメル・テクノロジー ロサルタンの経口医薬剤形態
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
FR2882259A1 (fr) * 2005-02-21 2006-08-25 Flamel Technologies Sa Forme pharmaceutique orale multimicroparticulaire a liberation modifiee de losartan
WO2006096462A1 (en) * 2005-03-03 2006-09-14 Elan Pharma International Limited Nanoparticulate compositions of heterocyclic amide derivatives
CN101111230B (zh) * 2005-03-29 2010-05-19 赢创罗姆有限责任公司 包含对活性成分具有调节释放作用的小丸的多颗粒药用形式
US20080069870A1 (en) * 2005-04-12 2008-03-20 Elan Corporation Pic Controlled Release Compositions Comprising a Cephalosporin for the Treatment of a Bacterial Infection
WO2006110802A1 (en) * 2005-04-12 2006-10-19 Elan Pharma International Limited Nanoparticulate and controlled release compositions comprising cyclosporine
CA2604192A1 (en) * 2005-04-12 2006-10-19 Elan Pharma International Limited Modified release compositions comprising a fluorocytidine derivative for the treatment of cancer
WO2006113310A2 (en) * 2005-04-13 2006-10-26 Elan Pharma International Limited Nanoparticulate and controlled release compositions comprising prostaglandin derivatives
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
US20100136106A1 (en) * 2005-06-08 2010-06-03 Gary Liversidge Modified Release Famciclovir Compositions
WO2008073068A1 (en) 2005-06-08 2008-06-19 Elan Pharma International Limited Nanoparticulate and controlled release compositions comprising cefditoren
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
KR101306635B1 (ko) 2005-06-27 2013-10-11 밸리언트 인터내셔널(바베이도스) 에스알엘 부프로피온염의 개질-방출 제형
WO2007012857A1 (en) * 2005-07-28 2007-02-01 University Of Hull Topical formulations containing sporopollenin
US8778395B2 (en) * 2005-08-11 2014-07-15 Andrx Labs, Llc Diltiazem controlled release formulation and method of manufacture
AU2006279643B2 (en) * 2005-08-15 2010-06-17 University Of Virginia Patent Foundation Neurorestoration with R(+) pramipexole
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
EP1945198A4 (en) * 2005-10-14 2009-08-26 Lundbeck & Co As H STABLE PHARMACEUTICAL FORMULATIONS CONTAINING ESCITALOPRAM AND BUPROPION
US7569605B2 (en) * 2005-10-14 2009-08-04 Forest Laboratories Holdings Limited Methods of treating central nervous system disorders with a low dose combination of escitalopram and bupropion
EP1933991A4 (en) 2005-10-15 2012-05-02 Atrium Medical Corp HYDROPHOBIC NETWORKED GEL FOR BIOABSORBIBLE MEDICINAL CARRIER COVERS
US20070098796A1 (en) 2005-10-31 2007-05-03 Rekhi Gurvinder S Controlled release compositions comprising a combination of isosorbide dinitrate and hydralazine hydrochrloride
US20070098791A1 (en) * 2005-10-31 2007-05-03 Rekhi Gurvinder S Controlled release compositions comprising a combination of isosorbide dinitrate and hydralazine hydrochloride
CA2631233C (en) * 2005-11-28 2011-11-08 Marinus Pharmaceuticals Ganaxolone formulations and methods for the making and use thereof
US8778924B2 (en) 2006-12-04 2014-07-15 Shionogi Inc. Modified release amoxicillin products
US8357394B2 (en) 2005-12-08 2013-01-22 Shionogi Inc. Compositions and methods for improved efficacy of penicillin-type antibiotics
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
WO2007090091A2 (en) 2006-01-27 2007-08-09 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
DK1993357T3 (da) * 2006-02-09 2014-04-22 Alba Therapeutics Corp Formuleringer af en tight junction effektor
KR20070091960A (ko) * 2006-03-08 2007-09-12 주식회사종근당 졸피뎀 또는 그의 염을 포함하는 안전한 제어방출형 제제조성물
US20070212414A1 (en) * 2006-03-08 2007-09-13 Penwest Pharmaceuticals Co. Ethanol-resistant sustained release formulations
DK2018160T3 (da) * 2006-03-16 2012-02-06 Tris Pharma Inc Modificeret depotformuleringer indeholdende lægemiddel-ionbytterharpikskomplekser
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
JP2009537565A (ja) 2006-05-16 2009-10-29 ノップ ニューロサイエンシーズ、インク． Ｒ（＋）およびｓ（−）プラミペキソール組成とそれを利用する方法
WO2007136664A2 (en) * 2006-05-16 2007-11-29 Flow Focusing, Inc. Antibiotic formulation and method of treatment
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
JP2009541360A (ja) * 2006-06-23 2009-11-26 エラン・ファルマ・インターナショナル・リミテッド ナノ粒子状メロキシカムおよび制御放出ヒドロコドンを含む組成物
CA2657409A1 (en) * 2006-07-12 2008-01-17 Elan Corporation, Plc Nanoparticulate formulations of modafinil
WO2008011596A2 (en) * 2006-07-21 2008-01-24 Lab International Srl Hydrophilic abuse deterrent delivery system
US8889184B2 (en) * 2006-09-07 2014-11-18 Losan Pharma Gmbh Particulate form of a pharmaceutical composition which is easy to swallow
WO2008027557A2 (en) * 2006-08-31 2008-03-06 Spherics, Inc. Topiramate compositions and methods of enhancing its bioavailability
MX2009002166A (es) 2006-08-31 2009-03-12 Eurand Inc Sistema de distribucion de farmacos, que comprenden soluciones solidas de farmacos debilmente basicos.
US20080064694A1 (en) * 2006-09-11 2008-03-13 Auriga Laboratories, Inc. Multi-Phase Release Methscopolamine Compositions
US20080069874A1 (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
CA2665841C (en) 2006-10-09 2016-04-05 Charleston Laboratories, Inc. Pharmaceutical compositions
WO2008052185A2 (en) * 2006-10-26 2008-05-02 Alba Therapeutics Corp Materials and methods for the treatment of celiac disease
US20110212175A1 (en) * 2006-10-30 2011-09-01 Hanall Biopharma Co., Ltd. Combination preparation comprising angiotensin-ii-receptor blocker and hmg-coa reductase inhibitor
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
US9492596B2 (en) 2006-11-06 2016-11-15 Atrium Medical Corporation Barrier layer with underlying medical device and one or more reinforcing support structures
EP2083875B1 (en) 2006-11-06 2013-03-27 Atrium Medical Corporation Coated surgical mesh
JP5489719B2 (ja) 2006-11-17 2014-05-14 スパーナス ファーマシューティカルズ インコーポレイテッド トピラマートの徐放性配合物
CA2669410C (en) * 2006-11-21 2015-07-14 Mcneil-Ppc, Inc. Modified release analgesic suspensions
KR20090091321A (ko) * 2006-11-28 2009-08-27 마리누스 파마슈티컬스 나노입자 제형, 이의 제조방법 및 이의 용도
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
CL2008000517A1 (es) 2007-02-20 2008-08-08 Eurand Pharmaceuticals Ltd Composicion que comprende al menos una enzima digestiva; forma farmaceutica que la comprende; envase que comprende un recipiente sellado; metodo para tratar o prevenir un desorden asociado con deficiencia en la enzima digestiva.
US20080227805A1 (en) * 2007-02-28 2008-09-18 Abbott Laboratories Sustained release parenteral formulations of buprenorphine
CA2681110A1 (en) 2007-03-14 2008-09-18 Knopp Neurosciences, Inc. Synthesis of chirally purified substituted benzothiazole diamines
US9833510B2 (en) * 2007-06-12 2017-12-05 Johnson & Johnson Consumer Inc. Modified release solid or semi-solid dosage forms
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
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
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
US20090060983A1 (en) * 2007-08-30 2009-03-05 Bunick Frank J Method And Composition For Making An Orally Disintegrating Dosage Form
EP2217213B1 (en) 2007-10-31 2017-05-24 Johnson & Johnson Consumer Inc. Orally disintegrative dosage form
JP2011506318A (ja) 2007-12-06 2011-03-03 デュレクト コーポレーション 経口医薬製剤
WO2009085306A1 (en) 2007-12-28 2009-07-09 Impax Laboratories, Inc. Controlled release formulations of levodopa and uses thereof
WO2009089494A2 (en) 2008-01-09 2009-07-16 Charleston Laboratories, Inc. Pharmaceutical compositions
US20100137442A2 (en) * 2008-02-01 2010-06-03 Xenoport, Inc. Sustained Release Particulate Oral Dosage Forms of (R)-Baclofen and Methods of Treatment
WO2009109856A2 (en) 2008-03-07 2009-09-11 Axcan Pharma Inc. Method for detecting infectious parvovirus in pharmaceutical preparations
CA2720108C (en) * 2008-03-11 2016-06-07 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
JP2012500283A (ja) 2008-08-19 2012-01-05 ノップ ニューロサイエンシーズ、インク． （ｒ）−プラミペキソールを使用した組成物並びにその方法
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
KR20110075011A (ko) * 2008-11-10 2011-07-05 (주)아모레퍼시픽 서방성 미립자 및 이의 제조방법
US8551517B2 (en) * 2008-12-16 2013-10-08 Kimberly-Clark Worldwide, Inc. Substrates providing multiple releases of active agents
WO2010078486A2 (en) 2008-12-31 2010-07-08 Upsher-Smith Laboratories, Inc. Opioid-containing oral pharmaceutical compositions and methods
EP2395840B1 (en) 2009-02-13 2020-04-15 Romark Laboratories, L.C. Controlled release pharmaceutical formulations of nitazoxanide
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
NZ595691A (en) * 2009-04-09 2013-06-28 Alkermes Pharma Ireland Ltd Drug delivery composition
JP2012524780A (ja) * 2009-04-21 2012-10-18 セレクタ バイオサイエンシーズ インコーポレーテッド Ｔｈ１バイアス応答をもたらす免疫ナノ治療薬（Ｉｍｍｕｎｏｎａｎｏｔｈｅｒａｐｅｕｔｉｃｓ）
BRPI1014278B8 (pt) * 2009-04-24 2021-05-25 Iceutica Pty Ltd método para produzir uma forma de dosagem compreendendo metaxolona, forma de dosagem, composição farmacêutica compreendendo a referida forma de dosagem e uso da mesma
WO2010138192A2 (en) 2009-05-27 2010-12-02 Selecta Biosciences, Inc. Nanocarriers possessing components with different rates of release
US20110003005A1 (en) * 2009-07-06 2011-01-06 Gopi Venkatesh Methods of Treating PDNV and PONV with Extended Release Ondansetron Compositions
CA2767576C (en) 2009-07-08 2020-03-10 Charleston Laboratories Inc. Pharmaceutical compositions comprising an antiemetic and an opioid analgesic
JP2013501068A (ja) 2009-08-05 2013-01-10 アイディニックス ファーマシューティカルズ インコーポレイテッド 大環状セリンプロテアーゼ阻害剤
US20110038910A1 (en) 2009-08-11 2011-02-17 Atrium Medical Corporation Anti-infective antimicrobial-containing biomaterials
PL399450A1 (pl) * 2009-08-31 2013-01-21 Depomed, Inc Utrzymujace sie w zoladku kompozycje farmaceutyczne do natychmiastowego i przedluzonego uwalniania acetaminofenu
CA2773521C (en) 2009-09-17 2017-01-24 Upsher-Smith Laboratories, Inc. A sustained-release product comprising a combination of a non-opioid amine and a non-steroidal anti-inflammatory drug
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
US8313768B2 (en) 2009-09-24 2012-11-20 Mcneil-Ppc, Inc. Manufacture of tablet having immediate release region and sustained release region
US8858210B2 (en) 2009-09-24 2014-10-14 Mcneil-Ppc, Inc. Manufacture of variable density dosage forms utilizing radiofrequency energy
WO2011056764A1 (en) 2009-11-05 2011-05-12 Ambit Biosciences Corp. Isotopically enriched or fluorinated imidazo[2,1-b][1,3]benzothiazoles
NZ600256A (en) 2009-12-02 2014-05-30 Aptalis Pharma Ltd Fexofenadine microcapsules and compositions containing them
BR112012014899A2 (pt) 2009-12-18 2017-03-14 Idenix Pharmaceuticals Inc composto, composição farmacêutica, método para tratar ou prevenir uma infecção por vírus de hepatite c em um sujeito, método para tratar , prevenir ou melhorar um ou mais sintomas de uma doença hepática ou distúrbio associado a uma infecção por vírus de hepatite c em um sujeito, método para inibir a replicação de um vírus em um hospedeiro, método para inibir a replicação de um vírus
US9198861B2 (en) 2009-12-22 2015-12-01 Mallinckrodt Llc Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans
US8597681B2 (en) 2009-12-22 2013-12-03 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
US9993793B2 (en) 2010-04-28 2018-06-12 The Procter & Gamble Company Delivery particles
US9186642B2 (en) 2010-04-28 2015-11-17 The Procter & Gamble Company Delivery particle
CA2798702A1 (en) 2010-05-11 2011-11-17 Cima Labs Inc. Alcoholresistant 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
SG186301A1 (en) 2010-06-16 2013-02-28 Takeda Pharmaceuticals Usa Inc Novel modified release dosage forms of xanthine oxidoreductase inhibitor or xanthine oxidase inhibitors
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
KR20130141469A (ko) 2010-09-01 2013-12-26 암비트 바이오사이언시즈 코포레이션 피라졸릴아미노퀴나졸린의 브롬화수소 염
EP2611796B1 (en) 2010-09-01 2016-04-20 Ambit Biosciences Corporation An optically active pyrazolylaminoquinazoline, and pharmaceutical compositions and methods of use thereof
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
EP2818160B1 (en) 2010-10-01 2017-11-08 Aptalis Pharma Limited Enteric coated, low-strength pancrelipase formulations
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
CA2825152A1 (en) 2011-01-31 2012-08-09 Celgene Corporation Pharmaceutical compositions of cytidine analogs and methods of use thereof
WO2012109398A1 (en) 2011-02-10 2012-08-16 Idenix Pharmaceuticals, Inc. Macrocyclic serine protease inhibitors, pharmaceutical compositions thereof, and their use for treating hcv infections
US8287903B2 (en) 2011-02-15 2012-10-16 Tris Pharma Inc Orally effective methylphenidate extended release powder and aqueous suspension product
PT2688557T (pt) 2011-03-23 2017-11-23 Ironshore Pharmaceuticals & Dev Inc Métodos e composições para o tratamento de distúrbio de défice de atenção
US8916588B2 (en) 2011-03-23 2014-12-23 Ironshore Pharmaceuticals & Development, Inc. Methods 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
US10292937B2 (en) 2011-03-23 2019-05-21 Ironshore Pharmaceuticals & Development, Inc. Methods of 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
US9603809B2 (en) 2011-03-23 2017-03-28 Ironshore Pharmaceuticals & Development, Inc. Methods of treatment of attention deficit hyperactivity disorder
US9119809B2 (en) 2011-03-23 2015-09-01 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
US10905652B2 (en) 2011-03-23 2021-02-02 Ironshore Pharmaceuticals & Development, Inc. Compositions for treatment of attention deficit hyperactivity disorder
US9283214B2 (en) 2011-03-23 2016-03-15 Ironshore Pharmaceuticals & Development, Inc. Compositions for treatment of attention deficit hyperactivity disorder
AU2012236937B2 (en) * 2011-03-25 2017-06-08 Selecta Biosciences, Inc. Osmotic mediated release synthetic nanocarriers
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
JP5869663B2 (ja) 2011-04-07 2016-02-24 ザ プロクター アンド ギャンブルカンパニー ポリアクリレートマイクロカプセルの付着が増大したシャンプー組成物
WO2012138710A2 (en) 2011-04-07 2012-10-11 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
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
US8658631B1 (en) 2011-05-17 2014-02-25 Mallinckrodt Llc Combination composition comprising oxycodone and acetaminophen for rapid onset and extended duration of analgesia
CN109172819A (zh) 2011-07-29 2019-01-11 西莱克塔生物科技公司 产生体液和细胞毒性t淋巴细胞（ctl）免疫应答的合成纳米载体
JP6004549B2 (ja) 2011-08-08 2016-10-12 アプタリス ファーマ リミテッドＡｐｔａｌｉｓ Ｐｈａｒｍａ Ｌｉｍｉｔｅｄ 消化酵素を含む組成物の溶出試験の方法
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
JP6120941B2 (ja) 2012-03-16 2017-04-26 アクシキン ファーマシューティカルズ インコーポレーテッド ３，５−ジアミノピラゾールキナーゼ阻害剤
US9511028B2 (en) 2012-05-01 2016-12-06 Johnson & Johnson Consumer Inc. Orally disintegrating tablet
US9445971B2 (en) 2012-05-01 2016-09-20 Johnson & Johnson Consumer Inc. Method of manufacturing solid dosage form
US9233491B2 (en) 2012-05-01 2016-01-12 Johnson & Johnson Consumer Inc. Machine for production of solid dosage forms
US9867880B2 (en) 2012-06-13 2018-01-16 Atrium Medical Corporation Cured oil-hydrogel biomaterial compositions for controlled drug delivery
CA2876371A1 (en) 2012-06-15 2013-12-19 Foundation For Biomedical Research And Innovation Prophylactic and/or therapeutic agent for mild cognitive impairment
MX362838B (es) 2012-07-12 2019-02-19 SpecGx LLC Composiciones farmacéuticas de liberación prolongada para disuadir el abuso de opioides que comprenden un plastómero, un elastómero y un plastificante delicuescente.
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
CA2880456A1 (en) 2012-08-15 2014-02-20 Tris Pharma, Inc. Methylphenidate extended release chewable tablet
US9662313B2 (en) 2013-02-28 2017-05-30 Knopp Biosciences Llc Compositions and methods for treating amyotrophic lateral sclerosis in responders
TW201521769A (zh) 2013-03-15 2015-06-16 Durect Corp 具有流變改質劑以減少溶解變異性之組成物
US10434194B2 (en) 2013-06-20 2019-10-08 Case Western Reserve University PSMA targeted nanobubbles for diagnostic and therapeutic applications
WO2015006708A1 (en) 2013-07-12 2015-01-15 Knopp Biosciences Llc 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
AU2014306222A1 (en) 2013-08-09 2016-02-18 Aptalis Pharma Ltd. Digestive enzyme composition suitable for enteral administration
PT3033081T (pt) 2013-08-13 2021-06-01 Knopp Biosciences Llc Composições e métodos para o tratamento da urticária crónica
ES2813674T3 (es) 2013-08-13 2021-03-24 Knopp Biosciences Llc Composiciones y métodos para el tratamiento de trastornos de células plasmáticas y trastornos prolinfocíticos de células b
NZ631142A (en) 2013-09-18 2016-03-31 Axikin Pharmaceuticals Inc Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors
WO2015042375A1 (en) 2013-09-20 2015-03-26 Idenix Pharmaceuticals, Inc. Hepatitis c virus inhibitors
PL3054929T3 (pl) 2013-10-07 2021-05-31 Impax Laboratories, Llc Mukoadhezyjne preparaty lewodopy i / lub estrów lewodopy o kontrolowanym uwalnianiu oraz ich zastosowania
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
US20150118300A1 (en) 2013-10-31 2015-04-30 Cima Labs Inc. Immediate Release Abuse-Deterrent Granulated Dosage Forms
CA2928899C (en) * 2013-11-04 2021-02-16 Jack William SCHULTZ Treatment of cognitive, emotional and mental ailments and disorders
JP6505721B2 (ja) 2014-01-10 2019-04-24 ジョンソン・アンド・ジョンソン・コンシューマー・インコーポレイテッド 高周波及び損失性被覆粒子を使用した錠剤の製造プロセス
WO2015134560A1 (en) 2014-03-05 2015-09-11 Idenix Pharmaceuticals, Inc. Solid forms of a flaviviridae virus inhibitor compound and salts thereof
KR102409739B1 (ko) 2014-03-20 2022-06-17 카펠라 테라퓨틱스, 인크. 암 치료용의 ｅｒｂｂ 티로신 키나제 억제제로서의 벤즈이미다졸 유도체
KR102416358B1 (ko) 2014-03-20 2022-07-07 카펠라 테라퓨틱스, 인크. 암 치료용의 ｅｒｂｂ 티로신 키나제 억제제로서의 벤즈이미다졸 유도체
EP3157568A1 (en) 2014-06-19 2017-04-26 Aptalis Pharma Limited Methods for removing viral contaminants from pancreatic extracts
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
AU2015317469B2 (en) 2014-09-19 2018-03-15 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
JP2017537165A (ja) 2014-12-03 2017-12-14 ヴェリセプト セラピューティクス、インク． 下部尿路系症状を対象とした徐放性ソラベグロンの組成物及び使用方法
TWI703133B (zh) 2014-12-23 2020-09-01 美商艾克斯基製藥公司 ３,５-二胺基吡唑激酶抑制劑
US11590228B1 (en) 2015-09-08 2023-02-28 Tris Pharma, Inc Extended release amphetamine compositions
JP2018530585A (ja) 2015-10-16 2018-10-18 マリナス ファーマシューティカルズ インコーポレイテッド ナノ粒子を含む注射可能な神経ステロイド製剤
DK3365321T3 (da) 2015-10-23 2024-01-15 B3Ar Therapeutics Inc Solabegron-zwitterion og anvendelser deraf
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
EP3463312A4 (en) * 2016-06-03 2020-02-05 Velicept Therapeutics, Inc. DOSING SCHEMES FOR BETA-3-ADRENOCEPTORAGONISTS AND ANTIMUS CARINICAS FOR THE TREATMENT AND PREVENTION OF SYMPTOMS OF THE LOWER URINARY PATHWAYS AND OVERACTIVE BLADDER
KR102518846B1 (ko) 2016-08-11 2023-04-05 오비드 테라퓨틱스 인크. 간질 장애의 치료를 위한 방법 및 조성물
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
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
US11020402B2 (en) 2018-10-15 2021-06-01 Axsome Therapeutics, Inc. Use of reboxetine to treat narcolepsy
US20200147093A1 (en) 2018-10-15 2020-05-14 Axsome Therapeutics, Inc. Use of esreboxetine to treat nervous system disorders such as fibromyalgia
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
US11266662B2 (en) 2018-12-07 2022-03-08 Marinus Pharmaceuticals, Inc. Ganaxolone for use in prophylaxis and treatment of postpartum depression
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
CA3145923A1 (en) 2019-08-05 2021-02-11 David Czekai Ganaxolone for use in treatment of status epilepticus
IL293525A (en) 2019-12-06 2022-08-01 Marinus Pharmaceuticals Inc Ganaxolone for use in the treatment of multiple sclerosis complex
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

Family Cites Families (214)

* Cited by examiner, † Cited by third party
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
EP0076158B1 (en) * 1981-09-30 1989-10-25 National Research Development Corporation 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
US4844896A (en) 1987-11-02 1989-07-04 Lim Technology Laboratories, Inc. Microencapsulated insecticidal pathogens
US4948586A (en) 1987-11-02 1990-08-14 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
AU3432689A (en) 1988-03-24 1989-10-16 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
US5196203A (en) 1989-01-06 1993-03-23 F. H. Faulding & Co. Limited Theophylline dosage form
US5330766A (en) 1989-01-06 1994-07-19 F. H. Faulding & Co. Limited Sustained release pharmaceutical composition
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
US5133974A (en) 1989-05-05 1992-07-28 Kv Pharmaceutical Company Extended release pharmaceutical formulations
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
GB2253346A (en) 1991-02-22 1992-09-09 John Rhodes Delayed release oral dosage forms for treatment of intestinal disorders
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
US5399363A (en) 1991-01-25 1995-03-21 Eastman Kodak Company Surface modified anticancer nanoparticles
US5145684A (en) * 1991-01-25 1992-09-08 Sterling Drug Inc. Surface modified drug nanoparticles
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
US5387421A (en) 1991-01-31 1995-02-07 Tsrl, Inc. Multi stage drug delivery system
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
JPH06511481A (ja) 1991-07-05 1994-12-22 ユニバーシティ オブ ロチェスター 気泡を取り込む超微小非凝集多孔質粒子
US5226902A (en) 1991-07-30 1993-07-13 University Of Utah Pulsatile drug delivery device using stimuli sensitive hydrogel
EP0664118B1 (en) 1991-10-04 1999-08-25 Yoshitomi Pharmaceutical Industries, Ltd. Sustained-release tablet
ES2106818T3 (es) * 1991-10-30 1997-11-16 Glaxo Group Ltd Composicion multicapa que contiene antagonistas de histamina o secotina.
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
NZ248813A (en) 1992-11-25 1995-06-27 Eastman Kodak Co Polymeric grinding media used in 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
PT621032E (pt) 1993-04-23 2001-01-31 Novartis Ag Dispositivo de distribuicao de libertacao controlada de farmaco
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
TW384224B (en) 1994-05-25 2000-03-11 Nano Sys Llc Method of preparing submicron particles of a therapeutic or diagnostic agent
US5411745A (en) 1994-05-25 1995-05-02 Euro-Celtique, S.A. Powder-layered morphine sulfate formulations
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
US5665331A (en) 1995-01-10 1997-09-09 Nanosystems L.L.C. Co-microprecipitation of nanoparticulate pharmaceutical agents with crystal growth modifiers
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
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
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
US5593657A (en) 1995-02-09 1997-01-14 Nanosystems L.L.C. Barium salt formulations stabilized by non-ionic and anionic stabilizers
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
US5591456A (en) 1995-02-10 1997-01-07 Nanosystems L.L.C. Milled naproxen with hydroxypropyl cellulose as a dispersion stabilizer
US5573783A (en) * 1995-02-13 1996-11-12 Nano Systems L.L.C. Redispersible nanoparticulate film matrices with protective overcoats
US5543133A (en) 1995-02-14 1996-08-06 Nanosystems L.L.C. Process of preparing x-ray contrast compositions containing nanoparticles
US5510118A (en) 1995-02-14 1996-04-23 Nanosystems Llc Process for preparing therapeutic 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
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
US5534263A (en) 1995-02-24 1996-07-09 Alza Corporation Active agent dosage form comprising a matrix and at least two insoluble bands
AU4990696A (en) 1995-02-24 1996-09-11 Nanosystems L.L.C. Aerosols containing nanoparticle dispersions
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
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
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
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
GB9514451D0 (en) * 1995-07-14 1995-09-13 Chiroscience Ltd Sustained-release formulation
CA2223629A1 (en) 1995-07-14 1997-02-06 Nicholas Robert Pope Therapeutic use of d-threo-methylphenidate
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
US5837284A (en) 1995-12-04 1998-11-17 Mehta; Atul M. Delivery of multiple doses of medications
US6355656B1 (en) * 1995-12-04 2002-03-12 Celgene Corporation Phenidate drug formulations having diminished abuse potential
US5908850A (en) * 1995-12-04 1999-06-01 Celgene Corporation Method of treating attention deficit disorders with d-threo methylphenidate
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
WO1997032573A1 (en) * 1996-03-08 1997-09-12 Nycomed Danmark A/S Modified release multiple-units dosage composition
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
ATE234602T1 (de) 1996-08-16 2003-04-15 Alza Corp Verabreichungsform zur abgabe von steigenden wirkstoffdosen
HRP970493A2 (en) * 1996-09-23 1998-08-31 Wienman E. Phlips Oral delayed immediate release medical formulation and method for preparing the same
AU4801497A (en) 1996-09-30 1998-04-24 Alza Corporation Dosage form and method for administering drug
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
EP0951278A2 (en) * 1997-01-03 1999-10-27 ELAN CORPORATION, Plc 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
WO1998035666A1 (en) 1997-02-13 1998-08-20 Nanosystems Llc Formulations of nanoparticle naproxen tablets
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
US5840329A (en) 1997-05-15 1998-11-24 Bioadvances Llc Pulsatile drug delivery system
CN1475208A (zh) 1997-07-01 2004-02-18 �Ʒ� 舍曲林的缓释剂型
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
CA2301883A1 (en) * 1997-09-11 1999-03-18 Nycomed Danmark A/S Modified release multiple-units compositions of non-steroid anti-inflammatory drug substances (nsaids)
DE59800870D1 (de) 1997-09-26 2001-07-19 Wacker Chemie Gmbh Verfahren zur herstellung von schutzkolloid-stabilisierten polymeren
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
KR20080083074A (ko) * 1998-06-03 2008-09-12 알자 코포레이션 연장된 약물 치료를 제공하기 위한 방법 및 장치
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
EP1126826B3 (en) 1998-11-02 2019-05-15 Alkermes Pharma Ireland Limited Multiparticulate modified release composition of methylphenidate
IT1303692B1 (it) 1998-11-03 2001-02-23 Chiesi Farma Spa Procedimento per la preparazione di sospensioni di particelle difarmaci da somministrare per inalazione.
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
US6428814B1 (en) 1999-10-08 2002-08-06 Elan Pharma International Ltd. Bioadhesive nanoparticulate compositions having cationic surface stabilizers
DE69915346T2 (de) * 1998-12-17 2004-07-22 Alza Corp., Mountain View Umwandlung von flüssigkeitsgefüllten gelatinkapseln in systeme mit gesteuerter wirkstoffabgabe durch mehrfache beschichtungen
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 PHARMACEUTICAL FORM FOR PULSED ADMINISTRATION OF (D-THREO) METHYLPHENIDATE AND ANOTHER CNS STIMULATING SUBSTANCE
DE60012520T3 (de) 1999-06-01 2009-06-25 Elan Pharma International 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
EP1136080A3 (en) 2000-03-14 2002-06-05 Pfizer Products Inc. Use of o-vanillin and o-vanillin/trolox combinations
BR0109764A (pt) 2000-03-23 2003-07-01 Clearant Inc Método para esterilização de um material biológico que é sensìvel à radiação de ionização
GB0009773D0 (en) 2000-04-19 2000-06-07 Univ Cardiff Particulate composition
CA2406696C (en) 2000-04-26 2009-06-30 Elan Pharma International Limited 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
DK1429731T3 (da) 2001-09-19 2007-05-14 Elan Pharma Int Ltd Nanopartikelformuleringer indeholdende insulin
ES2343405T3 (es) 2002-02-04 2010-07-30 Elan Pharma International Ltd. Composiciones nanoparticuladas que tienen lisozima como un estabilizador de superficie.
AU2003260803A1 (en) * 2002-08-30 2004-03-19 Orchid Chemicals And Pharmaceuticals Ltd. Sustained release pharmaceutical composition
PT1553927E (pt) 2002-09-11 2010-11-22 Elan Pharma Int Ltd Composições de agentes activos em nanopartículas estabilizadas em gel
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
NZ544007A (en) * 2003-05-07 2009-05-31 Samyang Corp Highly plastic granules for making fast melting tablets
CA2534924A1 (en) 2003-08-08 2005-02-24 Elan Pharma International Ltd. Novel metaxalone compositions
EP3498312A1 (en) * 2003-09-05 2019-06-19 Synthes GmbH Bone cement compositions having fiber-reinforcement and/or increased flowability
AR046410A1 (es) * 2003-09-18 2005-12-07 Cephalon Inc Composiciones farmaceuticas para la liberacion modificada de modafinilo
CA2860173C (en) * 2004-05-12 2021-12-14 The Brigham And Women's Hospital, Inc. Determining plasma gelsolin level to predict risk of developing infection
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
EP1888037A2 (en) 2005-05-10 2008-02-20 Elan Pharma International Limited Nanoparticulate clopidogrel formulations
CA2611741A1 (en) 2005-06-13 2006-12-28 Elan Pharma International, Limited Nanoparticulate clopidogrel and aspirin combination formulations

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101410094B (zh) * 2006-01-27 2013-04-17 阿普塔利斯制药股份有限公司 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
CN105025883A (zh) * 2013-03-29 2015-11-04 沃克哈特有限公司 右哌甲酯或其盐的调节释放的药物组合物

Also Published As

Publication number Publication date
JP2010270128A (ja) 2010-12-02
MY122159A (en) 2006-03-31
PT1126826E (pt) 2008-11-25
US6228398B1 (en) 2001-05-08
JP5463223B2 (ja) 2014-04-09
US20080279929A1 (en) 2008-11-13
SK287674B6 (sk) 2011-05-06
EP1126826B9 (en) 2009-07-08
EP1126826B3 (en) 2019-05-15
NO20012139D0 (no) 2001-04-30
KR100812832B1 (ko) 2008-03-11
KR20080032661A (ko) 2008-04-15
US6902742B2 (en) 2005-06-07
HUP0104039A3 (en) 2002-04-29
HK1050487A1 (en) 2003-06-27
CN100444830C (zh) 2008-12-24
SK5992001A3 (en) 2001-12-03
AU2004202078A1 (en) 2004-07-01
AU1335000A (en) 2000-05-22
DK1126826T3 (da) 2009-01-19
JP4613275B2 (ja) 2011-01-12
EP2020229A1 (en) 2009-02-04
PL348633A1 (en) 2002-06-03
BRPI9914977B8 (pt) 2021-05-25
PE20001322A1 (es) 2000-11-30
MXPA01004381A (es) 2005-09-08
US6730325B2 (en) 2004-05-04
US20040197405A1 (en) 2004-10-07
DK1126826T5 (en) 2018-10-22
AU2005247019A1 (en) 2006-02-02
US20030170304A1 (en) 2003-09-11
AU2005247019B2 (en) 2007-05-24
BR9914977B1 (pt) 2014-03-11
IL211075A0 (en) 2011-04-28
US20020054907A1 (en) 2002-05-09
ES2313797T3 (es) 2009-03-01
BR9914977A (pt) 2001-12-11
US20110008435A1 (en) 2011-01-13
IL211075A (en) 2012-03-29
EP2311442A1 (en) 2011-04-20
NO20012139L (no) 2001-06-27
NO343240B1 (no) 2018-12-17
US6793936B2 (en) 2004-09-21
CO5261536A1 (es) 2003-03-31
AU2009201786A1 (en) 2009-05-28
AU2009201786B2 (en) 2012-02-23
AU770645B2 (en) 2004-02-26
CA2348871C (en) 2009-04-14
KR20010111563A (ko) 2001-12-19
AR021858A1 (es) 2002-08-07
TR200101216T2 (tr) 2001-08-21
CZ20011539A3 (cs) 2001-12-12
EP1126826A4 (en) 2004-05-06
US8119163B2 (en) 2012-02-21
NZ511442A (en) 2003-02-28
RU2236847C2 (ru) 2004-09-27
ES2313797T7 (es) 2019-11-19
ID29852A (id) 2001-10-18
AU2004202078B2 (en) 2005-09-22
EP1126826B1 (en) 2008-10-15
DE69939748D1 (de) 2008-11-27
IL179379A0 (en) 2007-03-08
HU230454B1 (hu) 2016-07-28
CN1335768A (zh) 2002-02-13
CA2653839A1 (en) 2000-05-11
CA2348871A1 (en) 2000-05-11
DK1126826T6 (en) 2019-06-24
PL205109B1 (pl) 2010-03-31
EP1126826A1 (en) 2001-08-29
CY1110421T1 (el) 2015-04-29
IL179379A (en) 2011-03-31
US20030129237A1 (en) 2003-07-10
JP2002528485A (ja) 2002-09-03
HUP0104039A2 (hu) 2002-03-28
WO2000025752A1 (en) 2000-05-11
IL142896A0 (en) 2002-04-21
ATE411011T3 (de) 2008-10-15
KR20070051953A (ko) 2007-05-18
CZ303495B6 (cs) 2012-10-24
IL142896A (en) 2007-03-08

Similar Documents

Publication Publication Date Title
CN100444830C (zh) 多颗粒改进释放组合物
US20170000783A1 (en) Multiparticulate Modified Release Composition
SE509029C2 (sv) Långtidsverkande diklofenak-natriumpreparat
CN107224431A (zh) 非布司他改进的释放剂型及其制备方法
AU2007203497B2 (en) Multiparticulate modified release composition
AU2012202743B2 (en) Multiparticulate modified release composition
TWI292717B (en) Multiparticulate modified release composition

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
ASS Succession or assignment of patent right

Owner name: YILAN MEDICINE INTERNATIONAL CO., LTD.

Free format text: FORMER OWNER: ELAN CO.,LTD.,PLC

Effective date: 20090508

C41 Transfer of patent application or patent right or utility model
TA01 Transfer of patent application right

Effective date of registration: 20090508

Address after: Irish Claire

Applicant after: Elan Pharma Int Ltd

Address before: Dublin, Ireland

Applicant before: Ilan, PLC

C12 Rejection of a patent application after its publication
RJ01 Rejection of invention patent application after publication

Open date: 20030319

REG Reference to a national code

Ref country code: HK

Ref legal event code: WD

Ref document number: 1050487

Country of ref document: HK