CN1173695C - 控制释放与掩蔽味道的口服药物组合物 - Google Patents
控制释放与掩蔽味道的口服药物组合物 Download PDFInfo
- Publication number
- CN1173695C CN1173695C CNB008088942A CN00808894A CN1173695C CN 1173695 C CN1173695 C CN 1173695C CN B008088942 A CNB008088942 A CN B008088942A CN 00808894 A CN00808894 A CN 00808894A CN 1173695 C CN1173695 C CN 1173695C
- Authority
- CN
- China
- Prior art keywords
- protection
- active component
- substrate
- lipotropy
- compositions
- 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.)
- Expired - Lifetime
Links
Classifications
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2813—Inorganic compounds
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
- A61K9/2846—Poly(meth)acrylates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P11/08—Bronchodilators
-
- 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
- A61P11/14—Antitussive agents
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Inorganic Chemistry (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明涉及控制释放与掩蔽味道的组合物,含有一种或多种包容在三组分基质结构内的活性成分,该结构由连续的两亲性、亲脂性或惰性基质形成,最终包容或分散在亲水性基质中。大量控制活性成分溶解的系统的使用调节活性成分在水性和/或生物液体中的溶解速率,从而控制在胃肠道内的释放动力学。
Description
本发明涉及控制释放与掩蔽味道的组合物,含有一种或多种掺入在三组分基质结构内的活性成分,该结构由连续的两亲性、亲脂性或惰性基质形成,最终掺入或分散在亲水性基质中。大量用于控制活性成分溶解的系统的使用调节活性成分在水性和/或生物液体中的溶解速率,从而控制在胃肠道内的释放动力学,还可实现具有不适味道的性质或者对给药部位、特别是颊部黏膜具有刺激作用的活性成分的口服给药。
本发明的组合物可以含有如下治疗类活性成分:止痛药、抗炎药、心脏活性药物、镇静药、抗高血压药、消毒剂与局部抗微生物剂、抗震颤麻痹药、抗组胺药,本发明的组合物适合于口服给药或者局部作用于胃肠道的某些部位。
技术背景
持续、控制、延迟或至少有所改变的释放剂型可以按照不同的已知工艺进行制备:
1、惰性基质的使用,其中该基质结构的主要组分由于对水性液体的亲合性差,对溶剂渗入具有一定的抵抗性;这样的性质已知是亲脂性。
2、亲水性基质的使用,其中该基质结构的主要组分对溶剂前进具有较高的抵抗性,因为在其链中、主要在支链中存在强亲水性基团,显著增加了水合层内部的黏度。
3、生物可侵蚀基质的使用,它能够被一些生物腔内的酶所降解。
不过,所有上述操作都面临着缺点和瑕疵。
惰性基质:例如一般赋予活性成分以非线性、而是指数性(esponential)释放。
亲水性基质:具有线性行为,直至某些部分的活性成分已经被释放,然后它们显著偏离线性释放。
生物可侵蚀基质:是进行所谓“就地释放”所理想的,但是它们牵涉找到适合的酶或者对降解呈反应性的问题。此外,它们经常就地(in situ)释放代谢产物,后者在毒理学上并不是完全惰性的。
人们已经描述了大量基于惰性亲脂性基质的制剂:《Drug Dev.Ind.Pharm.》13(6),1001-1022,(1987)公开了利用不同量胶体二氧化硅作为亲脂性惰性基质的微孔化成分的方法,在该基质中掺有活性成分。
US 4,608,248描述了相同的惰性基质成管作用构思,其中将少量亲水性聚合物与各物质按不同基质材料的非连续共同渗入(compenetration)方式混合形成惰性基质。
EP 375,063公开了用于活性成分控制释放的多粒子颗粒剂的制备工艺,包括将聚合物或适合的物质共溶,与活性成分形成惰性基质,随后使所述溶液沉积在充当药具核心的惰性载体上。作为替代选择,将惰性载体与含有惰性聚合物和活性成分的溶液捏和,然后蒸发除去其溶解所用的有机溶剂,得到固体残余物。所得结构是一种“药库”,也就是沿最终形状的所有对称轴都不是宏观均匀的。
《化学与药学通报》(Chem.Pharm.Bull.)46(3),531-533也描述了相同的“药库”结构,通过沉积在丸粒表面上的惰性聚合物层的退火工艺,提高了实用性。
根据WO 93/00889所述工艺所得产品也属于“药库”结构,其中公开了亲水性基质中的丸粒的制备方法,包括:
-将活性成分与胃耐受性亲水性聚合物溶于有机溶剂;
-干燥所述悬液;
-随后在亲水性或亲脂性基质中捏和和配制丸粒,在两种类型应用之间没有有效性上的区别。
EP 0 453 001公开了在亲水性基质中插入“药库”结构的多粒子。基本的多粒子采用两层包衣膜,以降低活性成分的释放速率,pH-依赖性膜的目的是对胃的保护作用,pH-独立性甲基丙烯酸膜的目的是减缓水性液体的渗入。
WO 95/16451公开了仅由被胃耐受性膜包衣的亲水性基质所形成的组合物,用于控制活性成分的溶解速率。
在制备通常对胃肠道具有活性的药物的持续、控制释放剂型时,确保从给药后第一阶段的控制释放是很重要的,此时惰性基质在对数期内具有最大释放速率,也就是更高地偏离线性释放。
本发明已经达到了所述目标,也就是将两亲性基质结合在惰性基质内,后者与亲脂性聚合物配制在表面亲水性基质中。本发明的组合物是以不存在第一相为特征的,其中存在于基质表面的药物迅速溶解,本发明的组合物还以两亲层补偿了水性溶剂缺乏与形成内部惰性基质的亲脂性化合物的亲合性这一事实为特征的。
发明的公开
本发明提供了含有活性成分的控制释放与掩蔽味道的口服药物组合物,包含:
a)由熔点低于90℃的亲脂性化合物和可选的两亲性化合物组成的基质,其中至少部分掺有活性成分;
b)可选的两亲性基质;
c)外部亲水性基质,其中分散有亲脂性基质和可选的两亲性基质;
d)可选的其他赋形剂。
本发明的特定方面由含有一种或多种活性成分的控制释放的口服组合物组成,包含:
a)由两亲性化合物和熔点低于90℃的亲脂性化合物组成的基质,其中至少部分掺有活性成分;
b)外部亲水性基质,其中分散有亲脂性/两亲性基质;
c)可选的其他赋形剂。
本发明的另一方面提供含有一种或多种活性成分的掩蔽味道的口服组合物,包含:
-惰性或亲脂性基质,由C6-C20醇或C8-C20脂肪酸或脂肪酸与甘油或山梨糖醇或其他碳原子链不超过六的多元醇的酯组成;
-两亲性基质,由I或II型极性脂质或被C1-C4烷基链部分酯化的二醇类组成;
-含有上述基质的外部亲水性基质,主要由糖、糊精、多元醇或纤维素化合物或者由水凝胶构成;
-可选的赋形剂,赋予药物制剂以稳定性。
发明的详细说明
利用包括下列步骤的方法可以制备本发明的组合物:
a)首先通过简单的捏和或混合将活性成分包容(inglobate)在由具有两亲性质的化合物组成的基质或包衣中,下文将有进一步说明。活性成分与两亲性化合物的混合可以借助少量水-醇溶剂或者不用溶剂。
b)将a)中所得基质掺入在低熔点亲脂性赋形剂或赋形剂混合物中,同时加热以软化和/或熔化赋形剂本身,从而通过简单的分散作用掺入活性成分。在室温下冷却后,惰性基质成型,其体积有可能减小,得到含有活性成分粒子的惰性基质颗粒。
c)随后将惰性基质颗粒与一种或多种亲水性水可溶胀的赋形剂混合在一起。然后对混合物进行压制或压片。以这种方式,当片剂与生物液体接触时,形成高黏度溶胀层,它协调溶剂分子,充当水性液体本身渗入新结构内部的屏障。所述屏障拮抗由包容在惰性基质内的药物的溶解作用所致起始“爆发效应”,这也出现在亲水性基质内部。
按照本发明可以使用的两亲性化合物包括I或II型极性脂质(卵磷脂、磷脂酰胆碱、磷脂酰乙醇胺),神经酰胺,二元醇烷基醚(glycolalkyl ethers)、例如二甘醇一甲醚(Transcutol)。
亲脂性基质由选自如下的物质组成:不饱和和/或氢化的醇或脂酸、它的盐、酯或酰胺,脂肪酸单-、二-或三-甘油酯、它的聚乙氧基化衍生物,蜡,神经酰胺,胆固醇衍生物或其混合物,它们的熔点在40至90℃的范围内,优选为60至70℃。
如果需要的话,可以将脂肪酸钙盐掺入亲脂性基质,随后将其分散在由藻酸制成的亲水性基质中,因而在前面的溶剂渗入之后直至与分散其中的亲脂性基质颗粒接触,显著增加亲水性基质的黏度。
按照本发明的实施方式,首先制备具有高含量、通常为5至95%w/w活性成分的两亲性基质,也就是将活性成分或活性成分混合物分散在两亲性化合物混合物中,例如卵磷脂、其他II型极性脂质、表面活性剂或二甘醇一甲醚;然后将所得两亲性基质通常趁热与适合于形成惰性基质的亲脂性化合物混合或捏和,后者例如饱和或不饱和脂肪酸,例如棕榈酸、硬脂酸、肉豆蔻酸、月桂酸、laurylic酸或油酸,或者它们与其他短链脂肪酸的混合物,或者所述脂肪酸的盐或醇或衍生物,例如单-、二-或三-甘油酯或聚乙二醇酯或二甘醇酯,单独或者与蜡、神经酰胺、胆固醇衍生物或其他非极性脂质结合,混合比例是不同的,以便该亲脂性化合物混合物的熔点或软化温度在40至90℃的范围内,优选为60至70℃。
作为替代选择,形成惰性基质和两亲性基质的顺序是可以颠倒的,也就是在两亲性化合物内掺入惰性基质。
通过挤出和/或造粒方法或任意其他已知保留起始混合物的均匀分散性和基质结构的方法,可以将所得惰性亲脂性基质缩小为颗粒。
亲水性基质由已知为水凝胶的赋形剂组成,也就是这样的物质,它从干燥状态到水合状态经历所谓的“分子松弛”,也就是在赋形剂本身聚合链中存在的极性基团与大量水分子的协调作用之后,质量和重量有显著增加。
按照本发明可以使用的水凝胶实例是选自如下的化合物:丙烯酸或甲基丙烯酸的聚合物或共聚物、烷基乙烯基聚合物、羟基烷基纤维素、羧基烷基纤维素、多糖、糊精、果胶、淀粉与衍生物、天然或合成的树胶、藻酸。
在掩蔽味道的制剂的情况下,使用多元醇作为亲水性化合物也可能是有利的,例如木糖醇、麦芽糖醇和甘露糖醇。
将含有活性成分的亲脂性基质颗粒与上述亲水性化合物混合,二者的重量比通常为100∶0.5至100∶20(亲脂性基质∶亲水性基质)。可选地可以将一部分活性成分与亲水性物质混合,得到其中活性成分既分散在亲脂性基质中、也分散在亲水性基质中的组合物,所述组合物优选地是片剂、胶囊剂和/或微型片剂。
亲脂性和/或两亲性基质、形成水凝胶的化合物与可选的未包容在亲脂性基质中的活性成分的混合物经过压制,得到宏观上全体均匀的结构,也就是含有亲脂性颗粒在亲水性基质中的分散系的基质。将亲脂性基质颗粒用亲水性聚合物包衣,也可以得到相似的结果。
可根据本发明得到的片剂可以可选地用胃耐受性膜进行已知的包衣过程,膜例如由甲基丙烯酸聚合物(Eudragit)或纤维素衍生物(例如纤维素乙酰邻苯二甲酸酯)组成。
按照本发明适宜配制的活性成分包括:
-止痛药,例如对乙酰氨基酚、非那西丁、水杨酸钠;
-镇咳药,例如右美沙芬、磷酸可待因;
-支气管扩张药,例如沙丁胺醇、丙卡特罗;
-抗精神病药,例如氟哌啶醇、氯丙嗪;
-抗高血压药与冠脉扩张药,例如单硝酸异山梨醇酯与二硝酸异山梨醇酯、卡托普利;
-选择性β2拮抗药,例如沙丁胺醇、特布他林、麻黄碱、硫酸奥西那林;
-钙拮抗药,例如硝苯地平、尼卡地平、地尔硫、维拉帕米;
-抗震颤麻痹药,例如培高利特、卡比多巴、左旋多巴;
-非甾体抗炎药,例如酮洛芬、布洛芬、双氯芬酸、二氟尼柳、吡罗昔康、萘普生、酮咯酸、尼美舒利、苯噻丙酸、美沙拉秦(5-氨基水合物);
-抗组胺药,例如特非那定、氯雷他定;
-止泻药与肠道抗炎药,例如洛派丁胺、5-氨基水杨酸、奥沙拉秦、柳氮磺吡啶、布地奈德;
-解痉药,例如溴化辛基鎓;
-安定药,例如氯氮、奥沙西泮、美达西泮、阿普唑仑、多那西泮、劳拉西泮;
-口服抗糖尿病药,例如格列吡嗪、二甲双胍、苯乙双胍、格列齐特、格列本脲;
-泻药,例如比沙可啶、匹可硫酸钠;
-抗癫痫药,例如丙戊酸酯、卡马西平、苯妥英、加巴喷丁;
-抗肿瘤药,例如氟他胺、依托泊苷;
-口腔消毒剂或抗微生物剂,例如苯扎氯铵、氯化十六烷基吡啶或碘硫苯铵,和某些氨基衍生物,例如苄达明和氯己定,以及它们的盐和衍生物;
-氟化钠。
本发明的组合物可以进一步含有常规的赋形剂,例如生物粘附性赋形剂,例如壳聚糖、聚丙烯酰胺、天然或合成树胶、丙烯酸聚合物。
本发明的组合物可以含有一种以上的活性成分,它们各自可选地被包含在亲水性基质或惰性两亲性基质内,该组合物优选地是片剂、胶囊剂或微型片剂。
本发明的组合物呈片剂的形式,它在颊腔内或第一部分胃肠道内是可咀嚼的或可侵蚀的。
从溶解特征上来说,与水或水性液体接触导致水立即渗入基质的多表面层,由于水性溶剂的存在,基质因水凝胶聚合链膨胀而溶胀,引起前面水合的黏度增高,这防止溶剂本身的进一步渗入,线性减缓溶解过程至既定的点,可以位于厚度的大约一半,直至水的进一步渗入将导致亲水层的崩解和内容物的释放,不过,由惰性基质颗粒组成的内容物诱发这些结构特有的扩散机理,因此进一步减缓活性成分的溶解。
两亲性基质在惰性亲脂性基质内的存在可防止活性成分释放的所有不均匀性。两性部分中存在的表面活性剂促进多孔小管的可湿性,这些小管交叉在惰性基质中,防止或减少对溶剂渗入惰性基质内的抵抗性。
为了得到掩蔽味道的片剂,小心地选择亲水性基质的组分,以缩短活性物质通过渗入作用释放的时间,由亲水性化合物诱发的成管作用加速了渗入。
下列实施例更详细地阐述发明。
实施例1
在约50℃下,将10g大豆卵磷脂溶于50g水∶乙醇1∶3混合物,与500g 5-氨基水杨酸和20g溴化辛基鎓混合。匀化和干燥后,将所得混合物颗粒在捏和机内用20g巴西棕榈蜡和50g硬脂酸处理,加热直至均匀分散,然后冷挤压成小颗粒。将惰性基质颗粒装入混合机,向其中按顺序加入30g Carbopol 971P和65g羟丙基甲基纤维素。在用于均匀分散粉末的第一个混合步骤之后,加入60g微晶纤维素和5g硬脂酸镁。混合后,将最终的混合物压制成单重760mg/片。将所得片剂用纤维素乙酰邻苯二甲酸酯或聚甲基丙烯酸酯和增塑剂进行膜包衣,以提供胃耐受性,防止产品在胃内过早释放。
在模拟肠液中对所得片剂进行溶解试验,显示活性成分具有如下释放:60分钟后不超过30%,180分钟后不超过60%,5小时后不超过80%。
实施例2
将50g二甘醇一甲醚均匀分布在500g微晶纤维素上;然后加入100g布地奈德,混合至完全匀化。向该混合物中进一步加入400g布地奈德,然后分散在预先在60℃下加热的、含有100g巴西棕榈蜡和100g硬脂酸的捏和机中。捏和5分钟后,将混合物冷却至室温,挤出大小小于1mm的颗粒。
在适合的混合机内装入如上制备的基质颗粒和如下量的亲水性赋形剂:1500g羟丙基甲基纤维素和500g聚丙烯酸树脂(policarbophil)。
将各组分混合,直至基质均匀分散,然后加 2450g微晶纤维素、400g乳糖、100g胶体二氧化硅和50g硬脂酸镁。进一步混合5分钟后,将混合物压制成单重250mg/片。
实施例3
在造粒/捏和机内将35g二甘醇一甲醚用100g硬脂酸和55g巴西棕榈蜡熔化,将850g二甲双胍分散其中。加热该系统,进行活性成分在惰性基质中的造粒。向所得1040g制剂中加入110g羟丙基甲基纤维素和20g硬脂酸镁。
将最终的混合物压制成单重1170mg/片,相当于850mg活性成分。
在模拟肠液中对所得片剂进行溶解试验,显示活性成分具有如下释放:60分钟后不超过35%,180分钟后不超过60%,5小时后不超过80%。
实施例4
在造粒/捏和机内将120g溴化辛基鎓用30g硬脂酸和15g蜂蜡分散,其中10g二甘醇一甲醚已事先被熔化。
加热该系统,进行活性成分在惰性基质中的造粒。向所得10g制剂中加入5g羟丙基甲基纤维素、5g聚丙烯酸树脂、2g硬脂酸镁和3g微晶纤维素。
将最终的混合物压制成单重200mg/片,相当于120mg活性成分。
在模拟肠液中对所得片剂进行溶解试验,显示活性成分具有如下释放:60分钟后不超过25%,180分钟后不超过50%,5小时后不起过70%。
实施例5
将12g二甘醇一甲醚装在6g微晶纤维素和6g碳酸钙上,然后加入100g加巴喷丁,将混合物匀化。然后,加入800g在造粒/捏和机内用4.5g白蜡和5g硬脂酸分散的加巴喷丁。加热该系统,进行活性成分在惰性基质中的造粒。向所得916.5g制剂中加入39.5g羟丙基甲基纤维素、10g藻酸、11g硬脂酸镁和6g syloid。将最终的混合物压制成单重1000mg/片,相当于900mg活性成分。
实施例6
在造粒/捏和机内将10g(5g)二甘醇一甲醚熔化,然后用60g(30g)硬脂酸和30g(15g)黄蜡将50g(25g)卡比多巴和200g(100g)左旋多巴分散其中。
加热该系统,进行活性成分在惰性基质中的造粒。向所得340g(170g)制剂中加入20g(10g)羟丙基甲基纤维素、10g(5g)黄原胶、16g(8g)微晶纤维素、4g(2g)硬脂酸镁。
将最终的混合物压制成单重400(200)mg/片,相当于50(25)mg卡比多巴和200(100)mg左旋多巴(di levodopa)。
实施例7
将4g尼美舒利溶于50g二甘醇一甲醚,然后加入100g微晶纤维素,得到均匀混合物。
在造粒/捏和机内装入196g尼美舒利、50g硬脂酸和25g巴西棕榈蜡,再加入上述所得混合物。加热该系统,进行活性成分在惰性和两亲性基质系统中的造粒。
向所得425g颗粒中加入60g羟丙基甲基纤维素、5g聚丙烯酸树脂和10g硬脂酸镁。
将最终的混合物压制成单重500mg/片,相当于200mg活性成分。
在模拟肠液中对所得片剂进行溶解试验,显示活性成分具有如下释放:1小时后不超过25%,2小时后不超过40%,4小时后不超过60%,8小时后不超过90%。
实施例8
在造粒/捏和机内将20g二甘醇一甲醚熔化,然后用90g硬脂酸和40g巴西棕榈蜡将500g丙酰肉毒碱分散其中。加热该系统,进行活性成分在惰性/两亲性基质中的造粒。向所得650g制剂中加入60g羟丙基甲基纤维素和10g硬脂酸镁。
将最终的混合物压制成单重720mg/片,相当于500mg活性成分。
在模拟肠液中对所得片剂进行溶解试验,显示活性成分具有如下释放:60分钟后不超过40%,180分钟后不超过60%,4小时后不超过80%,8小时后不超过90%。
实施例9
将高速率造粒机预热至约70℃,放入1kg尼美舒利以及200g鲸蜡醇和25g甘油棕榈酰硬脂酸酯;将混合物捏和约15分钟,搅拌,同时降温至约30℃。加入所得惰性基质,在冷却期间保持搅拌和与50g大豆卵磷脂和50g乙二醇一甲醚捏和。通过适合大小的金属筛挤出颗粒,与50g羟丙基甲基纤维素、1320kg麦芽糖糊精、2kg乳糖-纤维素混合物、50g胶体二氧化硅、40g阿司帕坦、150g柠檬酸、75g矫味剂和65g硬脂酸镁混合。将最终的混合物压制成单重约500mg,硬度适合于在口内溶解,具有令人愉快的味道。
实施例10
操作同前实施例,用甘露糖醇代替糊精,用木糖醇代替乳糖-纤维素混合物,制备咀嚼片。所得片剂具有令人愉快的味道,经过咀嚼产生新鲜感,改善味道。
实施例11
操作同实施例9所述,但是具有下列组分:
-活性成分:布洛芬 100mg
-亲脂性/惰性基质组分:鲸蜡醇 15mg
-两亲性基质组分:大豆卵磷脂 8mg
-亲水性基质组分:甘露糖醇 167mg
-麦芽糖糊精 150mg
-甲基羟丙基纤维素 30mg
-助剂:阿司帕坦 15mg
-矫味剂 5mg
-胶体二氧化硅 5mg
-硬脂酸镁 5mg
得到单重500mg的片剂,经过颊给药逐渐被侵蚀,有效地掩蔽了活性成分的刺激性苦味。
实施例12
操作同实施例9所述,但是具有下列组分:
-活性成分:双氯芬酸钠 25mg
-亲脂性/惰性基质组分:鲸蜡醇 5mg
-甘油棕榈酰硬脂酸酯 5mg
-两亲性基质组分:大豆卵磷脂 7mg
-亲水性基质组分:木糖醇 168mg
-麦芽糖糊精 150mg
-羟丙基甲基纤维素 20mg
-助剂:阿司帕坦 5mg
-矫味剂 5mg
-胶体二氧化硅 5mg
-硬脂酸镁 5mg
得到单重400mg的片剂,经过颊给药逐渐被侵蚀,有效地掩蔽了活性成分的刺激性苦味。
实施例13
操作同实施例9所述,但是具有下列组分:
-活性成分:氯己定 2.5mg
-亲脂性/惰性基质组分:鲸蜡醇 0.5mg
-甘油棕榈酰硬脂酸酯 0.5mg
-两亲性基质组分:二甘醇一甲醚 0.3mg
-亲水性基质组分:木糖醇 38mg
-麦芽糖糊精 96mg
-羟丙基甲基纤维素 10mg
-助剂:阿司帕坦 3mg
-矫味剂 5mg
-胶体二氧化硅 2mg
-硬脂酸镁 2mg
得到单重150mg的片剂,经过颊给药逐渐被侵蚀,有效地掩蔽了活性成分的刺激性苦味。
实施例14
将高速率造粒机预热至约70℃,放入1kg尼美舒利以及125g鲸蜡醇;将混合物捏和约15分钟,搅拌,同时降温至约30℃,然后加入30g卵磷脂。然后通过适合大小的金属筛挤出所得混合物,与2.415kg乳糖、1.0kg麦芽糖糊精、50g羟丙基甲基纤维素、50g胶体二氧化硅、40g阿司帕坦、150g柠檬酸、75g矫味剂和65g硬脂酸镁混合。将最终的混合物压制成单重约500mg,硬度适合于在口内溶解,具有令人愉快的味道。
Claims (15)
1、含有活性成分的控制释放与掩蔽味道的口服药物组合物,包含:
a)由C6-C20醇或C8-C20脂肪酸或脂肪酸与甘油或山梨醇或其它碳原子数不超过六的多元醇的酯组成的基质;
b)两亲性基质;
c)外部亲水性基质,其中分散有亲脂性基质和两亲性基质;
d)药学可接受的赋形剂。
其呈片剂、胶囊剂、微型片剂的形式,其中该活性成分被分散在该亲水性基质与该亲脂性/两亲性基质中。
2、权利要求1所要求保护的控制释放的组合物,其包含亲脂性和亲水性基质,所述亲脂性基质由熔点为40-90℃的亲脂性化合物组成,其中该活性成分至少部分被包容。
3、权利要求2所要求保护的控制释放的组合物,其中所述亲脂性基质由熔点为60-70℃的亲脂性化合物组成。
4、如权利要求1所要求保护的组合物,其中该两亲性化合物是I或II型磷脂卵磷脂、磷脂酰胆碱、磷脂酰乙醇胺、神经酰胺、二元醇烷基醚、脂肪酸与聚乙二醇或二甘醇的酯。
5、权利要求1所要求保护的组合物,其中该亲脂性基质由选自如下的化合物组成:不饱和的和/或氢化的醇或脂肪酸、它的盐、酯或酰胺,脂肪酸单甘油酯、脂肪酸二甘油酯或脂肪酸三甘油酯它的聚乙氧基化衍生物,蜡,胆固醇衍生物。
6、权利要求1所要求保护的组合物,其中该亲水性基质由形成水凝胶的化合物组成。
7、权利要求6所要求保护的组合物,其中该亲水性基质由选自如下的化合物组成:丙烯酸或甲基丙烯酸的聚合物或共聚物、烷基乙烯基聚合物、羟基烷基纤维素、羧基烷基纤维素、多糖、糊精、果胶、淀粉与衍生物、藻酸、天然或合成的树胶、多元醇。
8、权利要求1所要求保护的组合物,包含胃耐受性包衣。
9、权利要求8所要求保护的组合物,其中该胃耐受性包衣由甲基丙烯酸聚合物或纤维素衍生物组成。
10、权利要求1所要求保护的组合物,呈片剂、胶囊剂、微型片剂的形式,其中该活性成分被完全包含在该亲脂性/两亲性基质内。
11、权利要求1所要求保护的组合物,呈片剂、胶囊剂、微型片剂的形式,其中该活性成分被分散在该亲水性基质与该亲脂性/两亲性基质中。
12、权利要求1所要求保护的组合物,其中该活性成分属于治疗类的止痛药、镇咳药、支气管扩张药、抗精神病药、选择性β2拮抗药、钙拮抗药、抗震颤麻痹药、非甾体抗炎药、抗组胺药、止泻药与肠道抗炎药、解痉药、安定药、口服抗糖尿病药、泻药、抗癫痫药、局部抗微生物剂。
13、权利要求11所要求保护的组合物,其中该活性成分选自美沙拉秦,5-氨基水杨酸、布地奈德、二甲双胍、溴化辛基鎓、加巴喷丁、卡比多巴、尼美舒利、丙酰肉毒碱、单硝酸异山梨醇酯与二硝酸异山梨醇酯、萘普生、布洛芬、酮洛芬、双氯芬酸、苯噻丙酸、氯己定、苄达明、碘硫苯铵、氯化十六烷基吡啶、苯扎氯铵、氟化钠。
14、权利要求1所要求保护的组合物,含有生物粘附性物质。
15、权利要求1所要求保护的药物组合物,呈片剂的形式,它在颊腔内或第一部分胃肠道内是可咀嚼的或可侵蚀的。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI99A001317 | 1999-06-14 | ||
IT1999MI001317A ITMI991317A1 (it) | 1999-06-14 | 1999-06-14 | Sistemi terapeutici a rilascio modificato per forma farmaceutiche orali |
IT2000MI000422A IT1317871B1 (it) | 2000-03-03 | 2000-03-03 | Sistemi terapeutici per forme farmaceutiche orali di principi attiviaventi sfavorevoli caratteristiche organolettiche. |
ITMI2000A000422 | 2000-03-03 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1355693A CN1355693A (zh) | 2002-06-26 |
CN1173695C true CN1173695C (zh) | 2004-11-03 |
Family
ID=26331662
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB008088942A Expired - Lifetime CN1173695C (zh) | 1999-06-14 | 2000-06-09 | 控制释放与掩蔽味道的口服药物组合物 |
Country Status (17)
Country | Link |
---|---|
US (20) | US7431943B1 (zh) |
EP (1) | EP1183014B1 (zh) |
JP (3) | JP4790950B2 (zh) |
CN (1) | CN1173695C (zh) |
AT (1) | ATE251449T1 (zh) |
AU (1) | AU5680100A (zh) |
CA (1) | CA2377301C (zh) |
DE (1) | DE60005819T2 (zh) |
DK (1) | DK1183014T3 (zh) |
ES (1) | ES2208349T3 (zh) |
HK (1) | HK1046244B (zh) |
MX (1) | MXPA01012889A (zh) |
NO (1) | NO331642B1 (zh) |
PT (1) | PT1183014E (zh) |
RU (1) | RU2246293C2 (zh) |
TR (1) | TR200200562T2 (zh) |
WO (1) | WO2000076478A1 (zh) |
Families Citing this family (93)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE251449T1 (de) | 1999-06-14 | 2003-10-15 | Cosmo Spa | Geschmacksmaskierte orale pharmazeutische zusammensetzungen mit kontrollierter abgabe |
ITMI991316A1 (it) * | 1999-06-14 | 2000-12-14 | Cip Ninety Two 92 S A | Composizioni farmaceutiche orali a rilascio modificato di mesalazina |
US8895064B2 (en) | 1999-06-14 | 2014-11-25 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
CA2359812C (en) | 2000-11-20 | 2004-02-10 | The Procter & Gamble Company | Pharmaceutical dosage form with multiple coatings for reduced impact of coating fractures |
ITMI20011337A1 (it) | 2001-06-26 | 2002-12-26 | Farmatron Ltd | Composizioni farmaceutiche orali a rilascio modificato del principio attivo |
US7612112B2 (en) | 2001-10-25 | 2009-11-03 | Depomed, Inc. | Methods of treatment using a gastric retained gabapentin dosage |
TWI312285B (en) | 2001-10-25 | 2009-07-21 | Depomed Inc | Methods of treatment using a gastric retained gabapentin dosage |
ITMI20012366A1 (it) * | 2001-11-09 | 2003-05-09 | Farmatron Ltd | Sistemi terapeutici stabilizzati a rilascio immediato e/o modificato per la somministrazione orale di principi attivi e/o eccipienti e/o ali |
TWI252111B (en) * | 2001-12-14 | 2006-04-01 | Solvay Pharm Gmbh | Matrix film tablet with controlled release of a natural mixture of conjugated estrogens |
FR2838349B1 (fr) * | 2002-04-15 | 2004-06-25 | Laurence Paris | Compositions liquides pour capsules molle a liberation prolongee et leur procede de fabrication |
AU2003232398A1 (en) * | 2002-06-07 | 2003-12-22 | Ranbaxy Laboratories Limited | Sustained release oral dosage forms of gabapentin |
US20040086566A1 (en) * | 2002-11-04 | 2004-05-06 | Alpharma, Inc. | Waxy matrix dosage forms |
FR2852843B1 (fr) | 2003-03-24 | 2008-05-23 | Karim Ioualalen | Systeme galenique permettant le masquage du gout |
CN1832735A (zh) * | 2003-07-29 | 2006-09-13 | 兰贝克赛实验室有限公司 | 与食物并行摄取加巴喷丁的新型给药方案及提高的口服生物有效度 |
WO2005072717A1 (ja) * | 2004-01-29 | 2005-08-11 | Dainippon Sumitomo Pharma Co., Ltd. | ビグアナイド系薬物の内服製剤 |
ITMI20040187A1 (it) * | 2004-02-06 | 2004-05-06 | Cosmo Spa | Composizioni farmaceutiche o dietetiche a base di acidi grassi a catena corta e zuccheri complessi per le disfunzioni intestinali |
ITMI20041295A1 (it) | 2004-06-25 | 2004-09-25 | Cosmo Spa | Composizioni farmaceutiche antimicrobiche orali |
US8497258B2 (en) | 2005-11-12 | 2013-07-30 | The Regents Of The University Of California | Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract |
US20090176882A1 (en) | 2008-12-09 | 2009-07-09 | Depomed, Inc. | Gastric retentive gabapentin dosage forms and methods for using same |
ES2288117B1 (es) * | 2006-05-08 | 2008-12-01 | Combino Pharm, S.L. | Composicion farmaceutica solida de gabapentina. |
CA2657769C (en) | 2006-07-19 | 2014-11-18 | The Board Of Regents Of The University Of Texas System | Preparations of phospholipids and pharmaceuticals containing 5-amino salicylic acid for the treatment of inflammatory bowel disease |
RU2009113557A (ru) * | 2006-09-12 | 2010-10-20 | Космо Текнолоджиз Лтд (Ie) | Фармацевтические композиции для перорального или ректального введения белковых веществ |
FR2913884A1 (fr) * | 2007-03-21 | 2008-09-26 | Oralance Pharma Sa | Systeme galenique hydrophobe non ionisable |
DE102007041588A1 (de) * | 2007-09-01 | 2009-03-05 | Lts Lohmann Therapie-Systeme Ag | Arzneimittel mit Hefe |
NZ589304A (en) * | 2008-04-29 | 2012-03-30 | Pharnext | Combination compositions for treating alzheimer disease and related disorders with zonisamide and acamprosate |
US9192578B2 (en) | 2008-08-20 | 2015-11-24 | Board Of Regents, The University Of Texas System | Hot-melt extrusion of modified release multi-particulates |
CA2638240C (en) * | 2008-08-29 | 2010-02-02 | Alexander Macgregor | Method of treating dysglycemia and glucose excursions |
AU2008243202B2 (en) * | 2008-11-11 | 2015-08-20 | Cosmo Technologies Ltd | Oral antimicrobial pharmaceutical compositions |
US9314444B2 (en) | 2009-01-12 | 2016-04-19 | Biokier, Inc. | Composition and method for treatment of NASH |
US20150224081A1 (en) * | 2009-01-12 | 2015-08-13 | Biokier, Inc. | Composition and method for treatment of diabetes |
HUE034551T2 (en) | 2009-01-12 | 2018-02-28 | Biokier Inc | Preparation and method of treating diabetes |
US9006288B2 (en) | 2009-01-12 | 2015-04-14 | Biokier, Inc. | Composition and method for treatment of diabetes |
US8945615B2 (en) * | 2009-02-17 | 2015-02-03 | Mylan Pharmaceuticals Inc. | Controlled release budesonide minitablets |
US8945616B2 (en) * | 2009-02-17 | 2015-02-03 | Mylan Pharmaceuticals Inc. | Controlled release budesonide minitablets |
DE102009012788A1 (de) * | 2009-03-13 | 2010-09-30 | J. Rettenmaier & Söhne Gmbh + Co. Kg | Verpressbares Tablettenmaterial mit ölhaltigem Wirkstoff, Tablette sowie Verfahren und Vorrichtung zu deren Herstellung |
CA2762179A1 (en) | 2009-05-18 | 2010-11-25 | Sigmoid Pharma Limited | Composition comprising oil drops |
GB0909680D0 (en) | 2009-06-05 | 2009-07-22 | Euro Celtique Sa | Dosage form |
US20110097401A1 (en) * | 2009-06-12 | 2011-04-28 | Meritage Pharma, Inc. | Methods for treating gastrointestinal disorders |
EA201270309A1 (ru) * | 2009-08-24 | 2012-07-30 | Абды Ибрахым Иладж Санайи Ве Тыджарет Аноным Сыркеты | Таблетки отилония, полученные прямым прессованием |
US9301938B2 (en) | 2009-09-23 | 2016-04-05 | Biokier, Inc. | Composition and method for treatment of diabetes |
EP2488163A1 (en) | 2009-10-16 | 2012-08-22 | Ranbaxy Laboratories Limited | A delayed release pharmaceutical composition of mesalamine |
WO2011057133A1 (en) | 2009-11-09 | 2011-05-12 | Spotlight Technology Partners Llc | Fragmented hydrogels |
NZ599524A (en) | 2009-11-09 | 2014-04-30 | Spotlight Technology Partners Llc | Polysaccharide based hydrogels |
IT1398643B1 (it) * | 2010-03-04 | 2013-03-08 | Cosmo Technologies Ltd | Composizione solida per la somministrazione orale di coloranti, e utilizzo diagnostico della stessa |
US9457079B2 (en) | 2010-05-12 | 2016-10-04 | The Trustees Of Columbia University In The City Of New York | Methods for producing enteroendocrine cells that make and secrete insulin |
WO2011154975A2 (en) | 2010-06-08 | 2011-12-15 | Cadila Healthcare Limited | Pharmaceutical compositions of metformin |
MX2013001190A (es) | 2010-07-29 | 2013-03-18 | Cosmo Technologies Ltd | Composiciones farmaceuticas y/o dieteticas con base en acidos grasos de cadena corta. |
IT1402047B1 (it) * | 2010-10-19 | 2013-08-28 | Cross Pharma Sa | Uso del mexiprostil nel trattamento delle malattie infiammatorie intestinali |
US11730709B2 (en) | 2010-10-29 | 2023-08-22 | Infirst Healthcare Limited | Compositions and methods for treating severe pain |
EP2446877A1 (en) * | 2010-10-29 | 2012-05-02 | Roquette Frères | Modified starch derivative-based matrix for colon targeting |
US11224659B2 (en) | 2010-10-29 | 2022-01-18 | Infirst Healthcare Limited | Solid solution compositions and use in severe pain |
US9271950B2 (en) | 2010-10-29 | 2016-03-01 | Infirst Healthcare Limited | Compositions for treating chronic inflammation and inflammatory diseases |
US8895537B2 (en) | 2010-10-29 | 2014-11-25 | Infirst Healthcare Ltd. | Compositions and methods for treating cardiovascular diseases |
US9744132B2 (en) | 2010-10-29 | 2017-08-29 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US9737500B2 (en) | 2010-10-29 | 2017-08-22 | Infirst Healthcare Limited | Compositions and methods for treating severe pain |
US10695432B2 (en) | 2010-10-29 | 2020-06-30 | Infirst Healthcare Limited | Solid solution compositions and use in severe pain |
US11202831B2 (en) | 2010-10-29 | 2021-12-21 | Infirst Healthcare Limited | Solid solution compositions and use in cardiovascular disease |
US9308213B2 (en) | 2010-10-29 | 2016-04-12 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US10695431B2 (en) | 2010-10-29 | 2020-06-30 | Infirst Healthcare Limited | Solid solution compositions and use in cardiovascular disease |
US9504664B2 (en) | 2010-10-29 | 2016-11-29 | Infirst Healthcare Limited | Compositions and methods for treating severe pain |
EP3498271A1 (en) * | 2011-05-02 | 2019-06-19 | Biokier, Inc. | Composition and method for treatment of diabetes |
AT511581A1 (de) * | 2011-05-26 | 2012-12-15 | G L Pharma Gmbh | Orale retardierende formulierung |
US10154964B2 (en) | 2011-09-07 | 2018-12-18 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
AU2011248587A1 (en) * | 2011-11-09 | 2013-05-23 | Cosmo Technologies Ltd | Controlled release and taste masking oral pharmaceutical composition |
CA2854054C (en) * | 2011-12-02 | 2020-05-12 | Pegasus Laboratories, Inc. | Amphipathic lipid-based sustained release compositions |
US10722458B2 (en) * | 2011-12-02 | 2020-07-28 | Pegasus Laboratories, Inc. | Amphipathic lipid-based sustained release compositions |
US20130209559A1 (en) | 2012-02-13 | 2013-08-15 | Santarus, Inc. | Method for treating intestinal diseases presenting at least one inflammatory component |
CA3008794C (en) | 2012-03-29 | 2021-03-16 | Therabiome, Llc | Gastrointestinal site-specific oral vaccination formulations active on the ileum and appendix |
EP2722058A1 (en) | 2012-10-19 | 2014-04-23 | Cosmo Technologies Ltd | Solid oral composition containing dyes for use in endoscopic diagnosis |
SG11201505245XA (en) * | 2013-01-14 | 2015-08-28 | Infirst Healthcare Ltd | Compositions and methods for treating severe pain |
CA2897878A1 (en) * | 2013-01-14 | 2014-07-17 | Infirst Healthcare Limited | Solid solution compositions and use in cardiovascular disease |
MX366317B (es) * | 2013-02-04 | 2019-07-03 | Infirst Healthcare Ltd | Composiciones y metodos para tratar la inflamacion cronica y las enfermedades inflamatorias. |
CA2904389C (en) | 2013-03-14 | 2018-09-18 | Jerome J. Schentag | Targeted gastrointestinal tract delivery of probiotic organisms and/or therapeutic agents |
US9240075B2 (en) | 2013-03-15 | 2016-01-19 | Daqri, Llc | Campaign optimization for experience content dataset |
CN103417507B (zh) * | 2013-08-23 | 2015-12-02 | 王显著 | 布地奈德药物组合物 |
US20150073057A1 (en) | 2013-09-06 | 2015-03-12 | Biokier, Inc. | Composition and method for treatment of diabetes |
ITMI20131578A1 (it) * | 2013-09-25 | 2015-03-26 | Giellepi S P A | Sostanza e formulazione per il trattamento delle malattie infiammatorie croniche intestinali |
IN2013MU03373A (zh) * | 2013-10-25 | 2015-07-17 | Cadila Healthcare Ltd | |
WO2015071812A1 (en) | 2013-11-18 | 2015-05-21 | Wockhardt Limited | Solid oral modified-release composition comprising budesonide or salt thereof |
GB2525227B (en) | 2014-04-16 | 2016-09-14 | Jaguar Land Rover Ltd | Bumper assembly method and apparatus |
WO2015200901A1 (en) | 2014-06-26 | 2015-12-30 | The Trustees Of Columbia University In The City Of New York | Inhibition of serotonin expression in gut enteroendocrine cells results in conversion to insulin-positive cells |
EP3006453A1 (en) * | 2014-10-08 | 2016-04-13 | Cosmo Technologies Ltd. | 17alpha-monoesters and 17alpha,21-diesters of cortexolone for use in the treatment of tumors |
CN104523717A (zh) * | 2015-01-06 | 2015-04-22 | 西南大学 | 西甲硅油奥替溴铵咀嚼片及其制备方法 |
US10954300B2 (en) | 2015-09-28 | 2021-03-23 | The Trustees Of Columbia University In The City Of New York | Use of pentoxifylline with immune checkpoint-blockade therapies for the treatment of melanoma |
AU2017364274A1 (en) | 2016-11-28 | 2019-05-30 | Cosmo Technologies Ltd. | Solid oral composition containing dyes |
WO2018129079A1 (en) * | 2017-01-03 | 2018-07-12 | Thermolife International, Llc | Method of isolating theacrine and composition comprising theacrine |
AU2018318123A1 (en) | 2017-08-15 | 2020-03-19 | Nephron Pharmaceuticals Corporation | Aqueous nebulization composition |
IL274414B1 (en) | 2017-11-10 | 2024-04-01 | Cosmo Technologies Ltd | Oral rifamycin SV preparations |
EP3501503A1 (en) * | 2017-12-22 | 2019-06-26 | Cosmo Technologies Ltd. | Solid delivery composition |
EP3613414A1 (de) | 2018-08-24 | 2020-02-26 | Dr. Falk Pharma Gmbh | Pellets mit mehrschichtiger struktur zur verzögerten freisetzung des wirkstoffs im distalen kolon |
CN110585164A (zh) * | 2019-10-08 | 2019-12-20 | 苏州弘森药业股份有限公司 | 一种艾司奥美拉唑镁碳酸氢钠胶囊的制作方法 |
EP4346858A1 (en) * | 2021-06-01 | 2024-04-10 | NBI Biosciences Pvt Ltd | Microbial-triggered oral intestinal drug delivery formulation and method of preparation thereof |
US11896719B2 (en) | 2022-01-24 | 2024-02-13 | Calliditas Therapeutics Ab | Pharmaceutical compositions |
Family Cites Families (68)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3133863A (en) | 1961-03-10 | 1964-05-19 | Strong Cobb Arner Inc | Sustained release therapeutic tablet compositions comprising organic solvent-gelled gums |
US3138525A (en) * | 1961-06-16 | 1964-06-23 | Hoffmann La Roche | Castor wax-amprotropine-resin compositions |
US3800051A (en) | 1970-09-21 | 1974-03-26 | Dow Chemical Co | Reducing serum cholesterol with certain substituted phenols |
US3965256A (en) | 1972-05-16 | 1976-06-22 | Synergistics | Slow release pharmaceutical compositions |
ZA825384B (en) | 1981-07-31 | 1983-05-25 | Tillott J B Ltd | Orally administrable pharmaceutical compositions |
JPH0759499B2 (ja) | 1984-02-10 | 1995-06-28 | ベンツォン ファーマ エイ/エス | 拡散被覆された複合単位服用剤 |
US4608248A (en) | 1985-11-08 | 1986-08-26 | Warner-Lambert Company | Process for time-controlled release of active ingredients |
JPS6348226A (ja) * | 1986-08-14 | 1988-02-29 | Ono Pharmaceut Co Ltd | 徐放性を有する経口投与用固形製剤 |
US5342625A (en) * | 1988-09-16 | 1994-08-30 | Sandoz Ltd. | Pharmaceutical compositions comprising cyclosporins |
IL92343A0 (en) | 1988-12-20 | 1990-07-26 | Gist Brocades Nv | Granulate for multiparticulate controlled release oral compositions,their preparation and oral pharmaceutical compositions containing them |
US5643602A (en) * | 1989-11-22 | 1997-07-01 | Astra Aktiebolag | Oral composition for the treatment of inflammatory bowel disease |
IT1246382B (it) | 1990-04-17 | 1994-11-18 | Eurand Int | Metodo per la cessione mirata e controllata di farmaci nell'intestino e particolarmente nel colon |
JP3011752B2 (ja) | 1990-10-23 | 2000-02-21 | フロイント産業株式会社 | 徐放性製剤およびその製造方法 |
US5183815A (en) | 1991-01-22 | 1993-02-02 | Merck & Co., Inc. | Bone acting agents |
AU1587392A (en) | 1991-03-15 | 1992-10-21 | Norwich Eaton Pharmaceuticals, Inc. | The use of 5-aminosalicylic acid in the treatment of irritable bowel syndrome - diarrheal phase or type (ibs-d) |
US5874063A (en) | 1991-04-11 | 1999-02-23 | Astra Aktiebolag | Pharmaceutical formulation |
TW209174B (zh) | 1991-04-19 | 1993-07-11 | Takeda Pharm Industry Co Ltd | |
US5320848A (en) | 1991-05-28 | 1994-06-14 | Affinity Biotech, Inc. | Chewable drug-delivery composition |
US5534501A (en) * | 1991-06-04 | 1996-07-09 | A Et S Biovecteurs | Particle for use as a milk fat globule substitute, composition containing same and process for the preparation of said particle |
IT1250654B (it) | 1991-07-08 | 1995-04-21 | Farcon Ag | Metodo per la preparazione di forme farmaceutiche orali a rilascio prolungato contenenti sostanze attive a solubilita' dipendente dal valore di ph. |
DE4131562A1 (de) | 1991-09-18 | 1993-03-25 | Medac Klinische Spezialpraep | Arzneistofftraeger aus festen lipidteilchen-feste lipidnanosphaeren (sln) |
WO1995016451A1 (fr) | 1992-06-22 | 1995-06-22 | Franck Arno Gouchet | Comprimes a liberation controlee de 4-asa |
US5472711A (en) | 1992-07-30 | 1995-12-05 | Edward Mendell Co., Inc. | Agglomerated hydrophilic complexes with multi-phasic release characteristics |
GB9224855D0 (en) * | 1992-11-27 | 1993-01-13 | Smithkline Beecham Plc | Pharmaceutical compositions |
SK87295A3 (en) * | 1993-01-08 | 1996-04-03 | Astra Ab | Novel colon or ileum-specific steroid derivatives |
US5686105A (en) * | 1993-10-19 | 1997-11-11 | The Procter & Gamble Company | Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery |
DE69425453T2 (de) * | 1993-04-23 | 2001-04-12 | Novartis Ag | Wirkstoffabgabevorrichtung mit gesteuerter Freigabe |
EP0752855B1 (en) * | 1994-03-30 | 1999-06-09 | Gs Development Ab | Use of fatty acid esters as bioadhesive substances |
US5447729A (en) | 1994-04-07 | 1995-09-05 | Pharmavene, Inc. | Multilamellar drug delivery systems |
ES2283503T3 (es) | 1994-04-22 | 2007-11-01 | Astellas Pharma Inc. | Sistema de liberacion de farmaco especifico de colon. |
EP0758329A1 (en) * | 1994-05-05 | 1997-02-19 | MERCK SHARP & DOHME LTD. | Morpholine derivatives and their use as antagonists of tachikinins |
US5849327A (en) | 1994-07-29 | 1998-12-15 | Advanced Polymer Systems, Inc. | Delivery of drugs to the lower gastrointestinal tract |
IL129547A (en) * | 1994-10-26 | 2001-01-11 | Novartis Ag | Pharmaceutical compositions comprising a macrolide and an acid |
IL116674A (en) | 1995-01-09 | 2003-05-29 | Mendell Co Inc Edward | Microcrystalline cellulose-based excipient having improved compressibility, pharmaceutical compositions containing the same and methods for the preparation of said excipient and of solid dosage form thereof |
SI9500173B (sl) | 1995-05-19 | 2002-02-28 | Lek, | Trofazna farmacevtska oblika s konstantnim in kontroliranim sproščanjem amorfne učinkovine za enkrat dnevno aplikacijo |
US5811388A (en) * | 1995-06-07 | 1998-09-22 | Cibus Pharmaceutical, Inc. | Delivery of drugs to the lower GI tract |
US5863910A (en) | 1996-01-12 | 1999-01-26 | Bolonick; Joel | Treatment of chronic inflammatory disorders of the gastrointestinal tract |
US5840332A (en) | 1996-01-18 | 1998-11-24 | Perio Products Ltd. | Gastrointestinal drug delivery system |
GB9613858D0 (en) | 1996-07-02 | 1996-09-04 | Cortecs Ltd | Hydrophobic preparations |
EP0919228A4 (en) | 1996-08-02 | 2001-12-12 | Hisamitsu Pharmaceutical Co | CAPSULES FOR ORAL PREPARATIONS AND CAPSULE PREPARATIONS FOR ORAL ADMINISTRATION |
US5891474A (en) * | 1997-01-29 | 1999-04-06 | Poli Industria Chimica, S.P.A. | Time-specific controlled release dosage formulations and method of preparing same |
AU7706598A (en) | 1997-05-30 | 1998-12-30 | Laboratorios Phoenix U.S.A., Inc. | Multi-layered osmotic device |
NZ503086A (en) | 1997-08-29 | 2002-03-01 | Upjohn Co | An orally administrable pharmaceutical composition comprising an inner core and two outer layers, which render it substantially free of unpleasant tastes |
DE29717252U1 (de) | 1997-09-26 | 1998-02-19 | Dr. Falk Pharma GmbH, 79108 Freiburg | Arzneimittelkit aus einem Budesonid-haltigen und einem Ursodesoxycholsäure-haltigen Arzneimittel zur Behandlung von cholestatischen Lebererkrankungen |
ES2252865T3 (es) * | 1997-09-26 | 2006-05-16 | Noven Pharmaceuticals, Inc. | Composiciones bioadhesivas y metodos para la administracion topica de agentes activos. |
US5965167A (en) | 1997-10-07 | 1999-10-12 | Sanghvi; Pradeepkumar P. | Dosage units |
US6607751B1 (en) | 1997-10-10 | 2003-08-19 | Intellipharamaceutics Corp. | Controlled release delivery device for pharmaceutical agents incorporating microbial polysaccharide gum |
IT1298575B1 (it) | 1998-02-06 | 2000-01-12 | Vectorpharma Int | Composizioni farmaceutiche in forma di nanoparticelle comprendenti sostanze lipidiche e sostanze antifiliche e relativo processo di |
US6239120B1 (en) * | 1998-03-17 | 2001-05-29 | Pharmalink Ab | Method and means for treating glomerulonephritis |
CA2274943A1 (en) | 1998-06-17 | 1999-12-17 | Stephen L. Wolman | Compositions for the treatment and prevention of inflammatory diseases of the gastrointestinal tract and methods and uses thereof |
DE19849737A1 (de) | 1998-10-28 | 2000-05-04 | Falk Pharma Gmbh | Kombinationsmittel zur Behandlung entzündlicher Darmerkrankungen |
ITMI991316A1 (it) | 1999-06-14 | 2000-12-14 | Cip Ninety Two 92 S A | Composizioni farmaceutiche orali a rilascio modificato di mesalazina |
US8895064B2 (en) | 1999-06-14 | 2014-11-25 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
ATE251449T1 (de) | 1999-06-14 | 2003-10-15 | Cosmo Spa | Geschmacksmaskierte orale pharmazeutische zusammensetzungen mit kontrollierter abgabe |
US6363635B1 (en) | 1999-10-22 | 2002-04-02 | Superior Bronze Corporation Of America | Memorial markers and method for producing the same |
JP4159217B2 (ja) | 1999-12-15 | 2008-10-01 | 花王株式会社 | 皮膚外用剤 |
ITMI20012599A1 (it) | 2001-12-11 | 2003-06-11 | Cosmo Spa | Composizioni farmaceutiche per la somministrazione orale di eparina osuoi derivati, utili per la terapia di malattie infiammatorie dell'int |
DE10214002A1 (de) | 2002-03-27 | 2003-10-09 | Roehm Gmbh | Pharmazeutische Formulierung für den Wirkstoff Budesonid |
GB0222612D0 (en) * | 2002-09-30 | 2002-11-06 | Univ Gent | Controlled delivery system for bioactive substances |
WO2004087109A1 (ja) | 2003-03-27 | 2004-10-14 | Hisamitsu Pharmaceutical Co., Inc. | 大腸送達性経口医薬製剤、大腸癌治療用経口医薬製剤および大腸炎治療用経口医薬製剤 |
DE102004043863A1 (de) | 2004-09-10 | 2006-03-16 | Nitec Pharma Ag | Tabletten mit orts- und zeitgesteuerter Wirkstofffreisetzung im Gastrointestinum |
US7715806B2 (en) | 2004-10-06 | 2010-05-11 | Broadcom Corporation | Method and system for diversity processing including using dedicated pilot method for closed loop |
BRPI0622008A2 (pt) | 2006-09-13 | 2011-12-20 | Procter & Gamble | métodos de tratamento para colite ulcerativa |
JP5132416B2 (ja) | 2008-05-08 | 2013-01-30 | キヤノン株式会社 | 画像処理装置およびその制御方法 |
PL2151235T3 (pl) | 2008-07-21 | 2011-05-31 | Dr Falk Pharma Gmbh | Preparat farmaceutyczny do leczenia górnego przewodu pokarmowego |
EP2298321A1 (en) | 2009-08-26 | 2011-03-23 | Nordic Pharma | Novel pharmaceutical compositions for treating IBD |
IT1398643B1 (it) | 2010-03-04 | 2013-03-08 | Cosmo Technologies Ltd | Composizione solida per la somministrazione orale di coloranti, e utilizzo diagnostico della stessa |
US8787888B2 (en) * | 2012-08-29 | 2014-07-22 | Facebook, Inc. | Sharing location information during a communication session |
-
2000
- 2000-06-09 AT AT00942044T patent/ATE251449T1/de active
- 2000-06-09 RU RU2002100367/15A patent/RU2246293C2/ru active
- 2000-06-09 PT PT00942044T patent/PT1183014E/pt unknown
- 2000-06-09 WO PCT/EP2000/005356 patent/WO2000076478A1/en active IP Right Grant
- 2000-06-09 ES ES00942044T patent/ES2208349T3/es not_active Expired - Lifetime
- 2000-06-09 DK DK00942044T patent/DK1183014T3/da active
- 2000-06-09 DE DE60005819T patent/DE60005819T2/de not_active Expired - Lifetime
- 2000-06-09 TR TR2002/00562T patent/TR200200562T2/xx unknown
- 2000-06-09 CA CA002377301A patent/CA2377301C/en not_active Expired - Lifetime
- 2000-06-09 CN CNB008088942A patent/CN1173695C/zh not_active Expired - Lifetime
- 2000-06-09 JP JP2001502812A patent/JP4790950B2/ja not_active Expired - Lifetime
- 2000-06-09 US US10/009,532 patent/US7431943B1/en not_active Expired - Lifetime
- 2000-06-09 EP EP00942044A patent/EP1183014B1/en not_active Expired - Lifetime
- 2000-06-09 MX MXPA01012889A patent/MXPA01012889A/es active IP Right Grant
- 2000-06-09 AU AU56801/00A patent/AU5680100A/en not_active Abandoned
-
2001
- 2001-12-14 NO NO20016108A patent/NO331642B1/no not_active IP Right Cessation
-
2002
- 2002-10-30 HK HK02107843.2A patent/HK1046244B/zh not_active IP Right Cessation
-
2005
- 2005-11-08 US US11/268,500 patent/US7410651B2/en not_active Expired - Lifetime
-
2006
- 2006-03-20 US US11/378,378 patent/US7410652B2/en not_active Expired - Lifetime
-
2008
- 2008-09-15 US US12/210,969 patent/US8029823B2/en not_active Ceased
-
2011
- 2011-01-04 JP JP2011000092A patent/JP5279851B2/ja not_active Expired - Lifetime
- 2011-01-04 JP JP2011000091A patent/JP5279850B2/ja not_active Expired - Lifetime
- 2011-09-30 US US13/249,839 patent/US20120021053A1/en not_active Abandoned
-
2012
- 2012-05-02 US US13/462,430 patent/US20120220559A1/en not_active Abandoned
- 2012-05-02 US US13/462,409 patent/US8293273B2/en not_active Expired - Lifetime
- 2012-05-22 US US13/477,592 patent/USRE43799E1/en not_active Expired - Fee Related
- 2012-08-29 US US13/597,867 patent/US20120321710A1/en not_active Abandoned
- 2012-09-14 US US13/617,138 patent/US8784888B2/en not_active Expired - Fee Related
- 2012-10-25 US US13/660,308 patent/US20130053360A1/en not_active Abandoned
-
2014
- 2014-06-18 US US14/308,279 patent/US9320716B2/en not_active Expired - Fee Related
- 2014-06-18 US US14/308,305 patent/US9532954B2/en not_active Expired - Fee Related
- 2014-10-15 US US14/514,967 patent/US20150056279A1/en not_active Abandoned
-
2016
- 2016-12-05 US US15/369,296 patent/US10064878B2/en not_active Expired - Fee Related
-
2017
- 2017-07-11 US US15/646,538 patent/US10105374B2/en not_active Expired - Fee Related
- 2017-07-11 US US15/646,330 patent/US10143698B2/en not_active Expired - Fee Related
-
2018
- 2018-09-17 US US16/132,718 patent/US20190015428A1/en not_active Abandoned
- 2018-09-24 US US16/139,672 patent/US20190022112A1/en not_active Abandoned
- 2018-12-28 US US16/234,951 patent/US20190134061A1/en not_active Abandoned
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1173695C (zh) | 控制释放与掩蔽味道的口服药物组合物 | |
CN1787811A (zh) | 口腔崩解片 | |
CN1674877A (zh) | 控释的多单位药物释放系统 | |
CN1086708A (zh) | 具有两阶段释放特征的固体药物及其生产方法 | |
CN1589139A (zh) | 调节释放坦洛新片剂 | |
CN1635894A (zh) | 糖尿病治疗剂型 | |
CN1929839A (zh) | 托哌酮的口服控释药物组合物 | |
CN1960709A (zh) | 递送多种药物形式的剂型 | |
TWI436760B (zh) | 阿利克侖之蓋崙(galenical)調配物 | |
TW201016210A (en) | Galenical formulations of organic compounds | |
CN101032472A (zh) | 治疗疼痛的布洛芬口腔崩解片及其制备方法 | |
CN101043876A (zh) | 包含可压性差的活性剂和生育酚聚乙二醇琥珀酸酯(tpgs)的片剂 | |
CN1634087A (zh) | 复方氨基葡萄糖盐缓释制剂及其制备方法和应用 | |
DK2956129T3 (en) | PHARMACEUTICAL COMPOSITIONS CONTAINING DEXKETOPROFEN AND TRAMADOL |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
ASS | Succession or assignment of patent right |
Owner name: COSMO TECHNOLOGY CO., LTD. Free format text: FORMER OWNER: COSMER S.R.L. Effective date: 20051118 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20051118 Address after: Italy Wiklo Patentee after: Cosmo S. P. A. Address before: Milan Italy Patentee before: Cosmer S.R.L. |
|
CX01 | Expiry of patent term |
Granted publication date: 20041103 |
|
CX01 | Expiry of patent term |