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1. 发明申请

US20060229713A1 Implantable medical device with openings for delivery of beneficial agents with combination release kinetics 有权
标题翻译：具有开口的植入式医疗装置，用于递送具有组合释放动力学的有益剂
公开(公告)号：US20060229713A1
公开(公告)日：2006-10-12
申请号：US11448319
申请日：2006-06-06
申请人： John Shanley , Theodore Parker , Thai Nguyen , Micheline Markey , Gary Steese-Bradley
发明人： John Shanley , Theodore Parker , Thai Nguyen , Micheline Markey , Gary Steese-Bradley
IPC分类号： A61F2/06
CPC分类号： A61F2/915 , A61F2/91 , A61F2002/91541 , A61F2002/91558 , A61F2210/0004 , A61F2250/0035 , A61F2250/0068
摘要： A method and system for delivering drug includes a first set of holes filled with a first formulation of the drug and a second set of holes filled with a second formulation of the same drug. This dual formulation or dual release kinetic system allows the creation of specifically tailored release kinetics by summation of multiple release kinetics.
摘要翻译：用于递送药物的方法和系统包括填充有药物的第一制剂的第一组孔和填充有相同药物的第二制剂的第二组孔。这种双重配方或双重释放动力学系统允许通过多次释放动力学的求和来创建专门定制的释放动力学。

2. 发明申请

US20050100577A1 Expandable medical device with beneficial agent matrix formed by a multi solvent system 审中-公开
标题翻译：具有由多溶剂体系形成的有益剂基质的可扩展医疗器械
公开(公告)号：US20050100577A1
公开(公告)日：2005-05-12
申请号：US10830566
申请日：2004-04-22
申请人： Theodore Parker , John Shanley , Micheline Markey
发明人： Theodore Parker , John Shanley , Micheline Markey
IPC分类号： A61F2/00 , A61F2/06 , A61F2/90 , A61L31/10 , A61L31/14 , A61L31/16 , A61K38/28 , A61K9/22 , A61K31/445 , A61K31/7076
CPC分类号： A61L31/148 , A61F2/91 , A61F2/915 , A61F2002/91541 , A61F2210/0076 , A61F2250/0068 , A61L31/10 , A61L31/14 , A61L31/146 , A61L31/16 , A61L2300/416 , A61L2300/43 , A61L2300/606 , A61L2300/61 , A61L2420/02 , A61L2420/08
摘要： A multi solvent drug delivery matrix formation method is used to place layers into a reservoir in a stent in a stepwise manner to achieve extended delivery of water soluble, sensitive, or difficult to deliver drugs. The multi solvent matrix formation method allows the formation of a drug reservoir with a layered morphology in which the mixing between layers is limited to allow the different layers to perform different functions in controlling drug delivery. A stent having a drug delivery matrix includes a first beneficial agent layer affixed to the stent by depositing a first solution of a first polymer and a first solvent, and a second beneficial agent layer affixed to the first beneficial agent layer by depositing a second solution of a second polymer and a second solvent. The second solvent is selected so that the first polymer is substantially insoluble in the second solvent to prevent degradation of the first polymer during deposition of the second polymer. A therapeutic agent is provided in the first beneficial agent layer or the second beneficial agent layer to form a drug delivery matrix.
摘要翻译：使用多溶剂药物递送基质形成方法以逐步方式将层放置在支架中的储存器中以实现水溶性，敏感或难以递送的药物的延长递送。多溶剂基质形成方法允许形成具有分层形态的药物储存器，其中层之间的混合被限制以允许不同的层在控制药物递送中执行不同的功能。具有药物递送基质的支架包括通过沉积第一聚合物和第一溶剂的第一溶液而固定到支架上的第一有益剂层和通过沉积第一有益剂层的第二溶液第二聚合物和第二溶剂。选择第二溶剂使得第一聚合物基本上不溶于第二溶剂以防止第二聚合物沉积期间第一聚合物的降解。在第一有益剂层或第二有益剂层中提供治疗剂以形成药物递送基质。

3. 发明授权

US06635280B2 Extending the duration of drug release within the stomach during the fed mode 有权
公开(公告)号：US06635280B2
公开(公告)日：2003-10-21
申请号：US10045823
申请日：2001-11-06
申请人： John W. Shell , Jenny Louie-Helm , Micheline Markey
发明人： John W. Shell , Jenny Louie-Helm , Micheline Markey
IPC分类号： A61K926
CPC分类号： A61K9/0065 , A61K9/2013 , A61K9/2031 , A61K9/205 , A61K9/2054
摘要： Drugs are formulated as unit oral dosage forms by incorporating them into polymeric matrices comprised of hydrophilic polymers that swell upon imbibition of water to a size that is large enough to promote retention of the dosage form in the stomach during the fed mode. The oral formulation is designed for gastric retention and controlled delivery of an incorporated drug into the gastric cavity, and thus administered, the drug is released from the matrix into the gastric fluid by solution diffusion. The swollen polymeric matrix, having achieved sufficient size, remains in the gastric cavity for several hours if administered while the patient is in the fed mode, and remains intact long enough for substantially all of the drug to be released before substantial dissolution of the matrix occurs. The swelling matrix lowers the accessibility of the gastric fluid to the drug and thereby reduces the drug release rate. This process, together with diffusion retardation by selection of specific polymers, polymer molecular weights, and other variables, results in a sustained and controlled delivery rate of the drug to the gastric cavity.

4. 发明授权

US06340475B2 Extending the duration of drug release within the stomach during the fed mode 有权
标题翻译：在喂食模式期间延长胃内药物释放的持续时间
公开(公告)号：US06340475B2
公开(公告)日：2002-01-22
申请号：US09282233
申请日：1999-03-29
申请人： John W. Shell , Jenny Louie-Helm , Micheline Markey
发明人： John W. Shell , Jenny Louie-Helm , Micheline Markey
IPC分类号： A61K926
CPC分类号： A61K9/0065 , A61K9/2013 , A61K9/2031 , A61K9/205 , A61K9/2054
摘要： Drugs are formulated as unit oral dosage forms by incorporating them into polymeric matrices comprised of hydrophilic polymers that swell upon imbibition of water to a size that is large enough to promote retention of the dosage form in the stomach during the fed mode. The oral formulation is designed for gastric retention and controlled delivery of an incorporated drug into the gastric cavity, and thus administered, the drug is released from the matrix into the gastric fluid by solution diffusion. The swollen polymeric matrix, having achieved sufficient size, remains in the gastric cavity for several hours if administered while the patient is in the fed mode, and remains intact long enough for substantially all of the drug to be released before substantial dissolution of the matrix occurs. The swelling matrix lowers the accessibility of the gastric fluid to the drug and thereby reduces the drug release rate. This process, together with diffusion retardation by selection of specific polymers, polymer molecular weights, and other variables, results in a sustained and controlled delivery rate of the drug to the gastric cavity.
摘要翻译：将药物配制成单位口服剂型，通过将它们并入由亲水性聚合物组成的聚合物基质中，所述亲水性聚合物在吸水时膨胀至足够大以在给药模式期间促进剂型在胃中的保留。口服制剂设计用于胃内保留和控制递送并入药物进入胃腔，并因此施用，通过溶液扩散将药物从基质释放到胃液中。已经达到足够大小的溶胀的聚合物基质在患者处于喂养模式的同时在胃腔内保留数小时，并保持完整的时间足以使基本上所有的药物在基质溶解之前被释放出来。溶胀基质降低胃液对药物的可及性，从而降低药物释放速率。该方法与通过选择特定聚合物，聚合物分子量和其他变量的扩散阻滞一起导致药物持续且受控制的胃腔输送速率。

5. 发明授权

US07405238B2 Pharmacological inducement of the fed mode for enhanced drug administration to the stomach 有权
标题翻译：用于增强药物给予胃的喂养模式的药理学诱导
公开(公告)号：US07405238B2
公开(公告)日：2008-07-29
申请号：US10235076
申请日：2002-09-04
申请人： Micheline Markey , John W. Shell , Bret Berner
发明人： Micheline Markey , John W. Shell , Bret Berner
IPC分类号： A61K31/21 , A61K47/00
CPC分类号： A61K9/0065 , A61K9/209 , A61K9/5084
摘要： Drugs intended for absorption in the stomach or upper intestinal tract are administered in oral drug delivery systems in conjunction with any of various substances that have been discovered to function as potent agents for inducing the fed mode. By inducing the onset of the fed mode, these agents cause the stomach to prolong its retention of the drug delivery system, which is either large enough to be retained in the stomach during the fed mode or swells or expands to such a size upon ingestion. The fed mode inducing agents include the following compounds and their salts: glycine and glycylglycine, xylitol and related sugar alcohols, sodium and other metal docusates, β-casomorphins, α-lipoic acid and similarly structured acids, 2,2-diaryl-4-(4′-aryl-4′-hydroxypipendino)butyramides, arginine, Trp-Trp, alkylpyridinium halides, dihydroxybenzoic acids, and potent sweeteners such as aspartame, aspartic acid, acesulfame, and stevioside.
摘要翻译：预期用于在胃或上肠道中吸收的药物在口服药物递送系统中与已被发现用作诱导喂养模式的有效药剂的任何各种物质一起施用。通过诱导进食模式的发作，这些药物引起胃部延长其药物递送系统的保留，药物递送系统的大小足以在进食模式期间保留在胃中，或者在摄食时膨胀或膨胀至这样的大小。饲喂模式诱导剂包括以下化合物及其盐：甘氨酸和甘氨酰甘氨酸，木糖醇和相关糖醇，钠和其他金属多库酯，β-半胱氨酸，α-硫辛酸和类似结构的酸，2,2-二芳基-4- （4'-芳基-4'-羟基磷脂）丁酰胺，精氨酸，Trp-Trp，烷基吡啶鎓卤化物，二羟基苯甲酸，以及强效甜味剂，如阿斯巴甜，天冬氨酸，乙酰磺胺酸和甜菊苷。

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