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1. 发明授权

US6120807A Prolonged release of GM-CSF 失效
标题翻译：长时间释放GM-CSF
公开(公告)号：US6120807A
公开(公告)日：2000-09-19
申请号：US185213
申请日：1998-11-03
申请人： Wayne Gombotz , Dean Pettit , Susan Pankey
发明人： Wayne Gombotz , Dean Pettit , Susan Pankey
IPC分类号： A61K9/14 , A61K9/16 , A61K31/00 , A61K38/19 , A61K38/22 , A61K47/34 , A61P37/00 , A61P37/04 , A61K9/50
CPC分类号： A61K9/0019 , A61K38/193 , A61K9/0024 , A61K9/06 , A61K9/1635 , A61K9/1641 , A61K9/1647 , Y10T428/2989
摘要： Formulations for controlled, prolonged release of GM-CSF have been developed. These are based on solid microparticles formed of the combination of biodegradable, synthetic polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and copolymers thereof with excipients and drug loadings that yield zero order or first order release, or multiphasic release over a period of approximately three to twenty one days, preferably one week, when administered by injection. In the preferred embodiment, the microparticles are microspheres having diameters in the range of 10 to 60 microns, formed of a blend of PLGA having different molecular weights, most preferably 6,000, 30,000 and 41,000. Other embodiments hare been developed to alter the release kinetics or the manner in which the drug is distributed in vivo. For example, in some cases a polymer is selected which elicits a mild inflammatory reaction, for example, PLGA and polyanhydrides can act as chemoattractant, either due to the polymer itself or minor contaminants in the polymer, or polymers which are bioadhesive are used for transmucosal or oral delivery. In another embodiment, the GM-CSF is administered in a hydrogel which can be injected subcutaneous or at a specific site for controlled release. The microparticles or hydrogel are administered to the patient in an amount effect to stimulate proliferation of hematopoietic cells, especially white cells.
摘要翻译：已经开发了控制，长期释放GM-CSF的制剂。这些基于由生物可降解的合成聚合物如聚（乳酸）（PLA），聚（乙醇酸）（PGA））及其与赋形剂的共聚物和药物负载的组合形成的固体微粒，其产生零级或一级当通过注射给药时，在约3至20天，优选1周的时间内释放或多相释放。在优选的实施方案中，微粒是具有10至60微米范围内的直径的微球，由具有不同分子量，最优选6,000,300和41,000的PLGA的共混物形成。已经开发了其它实施方案来改变释放动力学或药物在体内分布的方式。例如，在一些情况下，选择引起轻度炎症反应的聚合物，例如PLGA和聚酐可以作为化学引诱剂，这是由于聚合物本身或聚合物中的微量污染物，或生物粘附剂的聚合物用于经粘膜或口服。在另一个实施方案中，GM-CSF以可以皮下注射或在特定部位注射用于控制释放的水凝胶施用。将微粒或水凝胶以刺激造血细胞，特别是白细胞增殖的量施用于患者。

2. 发明授权

US5942253A Prolonged release of GM-CSF 失效
标题翻译：长时间释放GM-CSF
公开(公告)号：US5942253A
公开(公告)日：1999-08-24
申请号：US542445
申请日：1995-10-12
申请人： Wayne Gombotz , Dean Pettit , Susan Pankey , James Ronald Lawter , W. James Huang
发明人： Wayne Gombotz , Dean Pettit , Susan Pankey , James Ronald Lawter , W. James Huang
IPC分类号： A61K9/14 , A61K9/16 , A61K31/00 , A61K38/19 , A61K38/22 , A61K47/34 , A61P37/00 , A61P37/04 , A61K9/50 , A61F2/02 , A61K9/48
CPC分类号： A61K9/0019 , A61K38/193 , A61K9/0024 , A61K9/06 , A61K9/1635 , A61K9/1641 , A61K9/1647 , Y10T428/2989
摘要： Formulations for controlled, prolonged release of GM-CSF have been developed. These are based on solid microparticles formed of the combination of biodegradable, synthetic polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and copolymers thereof with excipients and drug loadings that yield zero order or first order release, or multiphasic release over a period of approximately three to twenty one days, preferably one week, when administered by injection. In the preferred embodiment, the microparticles are microspheres having diameters in the range of 10 to 60 microns, formed of a blend of PLGA having different molecular weights, most preferably 6,000, 30,000 and 41,000. Other embodiments have been developed to alter the release kinetics or the manner in which the drug is distributed in vivo. For example, in some cases a polymer is selected which elicits a mild inflammatory reaction, for example, PLGA and polyanhydrides can act as chemoattractant, either due to the polymer itself or minor contaminants in the polymer, or polymers which are bioadhesive are used for transmucosal or oral delivery. In another embodiment, the GM-CSF is administered in a hydrogel which can be injected subcutaneous or at a specific site for controlled release. The microparticles or hydrogel are administered to the patient in an amount effect to stimulate proliferation of hematopoietic cells, especially white cells.
摘要翻译：已经开发了控制，长期释放GM-CSF的制剂。这些基于由生物可降解的合成聚合物如聚（乳酸）（PLA），聚（乙醇酸）（PGA））及其与赋形剂的共聚物和药物负载的组合形成的固体微粒，其产生零级或一级当通过注射给药时，在约3至20天，优选1周的时间内释放或多相释放。在优选的实施方案中，微粒是具有10至60微米范围内的直径的微球，由具有不同分子量，最优选6,000,300和41,000的PLGA的共混物形成。已经开发了其它实施方案来改变药物在体内分布的释放动力学或方式。例如，在一些情况下，选择引起轻度炎症反应的聚合物，例如PLGA和聚酐可以作为化学引诱剂，这是由于聚合物本身或聚合物中的微量污染物，或生物粘附剂的聚合物用于经粘膜或口服。在另一个实施方案中，GM-CSF以可以皮下注射或在特定部位注射用于控制释放的水凝胶施用。将微粒或水凝胶以刺激造血细胞，特别是白细胞增殖的量施用于患者。

3. 发明授权

US4652529A Serum pretreatment for tricyclic antidepressant drug assays 失效
标题翻译：三环抗抑郁药物测定的血清预处理
公开(公告)号：US4652529A
公开(公告)日：1987-03-24
申请号：US657319
申请日：1984-10-02
申请人： Christine G. Collins , Susan Pankey , Anna Jaklitsch
发明人： Christine G. Collins , Susan Pankey , Anna Jaklitsch
IPC分类号： G01N33/94 , G01N30/02 , G01N33/50
CPC分类号： G01N33/9466 , Y10T436/141111
摘要： Serum is passed through a column containing alkylated silica gel. The column is then washed with a mixture comprising from about 50 to 85 volume percent of an aqueous buffered medium of pH from about 3.5 to 5.0 and from about 15 to 50 volume percent of an organic solvent containing from 1 to 6 carbon atoms and from 1 to 5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. The tricyclic antidepressant drug is removed from the column with an eluent mixture comprising from about 0 to 75 volume percent of an aqueous buffered medium of pH of about from 6 to 8 and from about 25 to 100 volume percent of one or more organic solvents containing from 1 to 6 carbon atoms and from 1 to 5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. In this way, a tricyclic antidepressant drug sample, free from interfering metabolites, for use in assay determinations is obtained.
摘要翻译：血清通过含有烷基化硅胶的柱。然后用包含约50至85体积％的pH为约3.5至5.0的含水缓冲介质和约15至50体积％的含有1至6个碳原子的有机溶剂和1份至5个选自氧，氮和硫的杂原子。使用洗脱剂混合物从柱中除去三环抗抑郁药物，洗脱剂混合物包含约0至75体积％的pH为约6至8和约25至100体积％的含水缓冲介质，一种或多种含有 1至6个碳原子和1至5个选自氧，氮和硫的杂原子。以这种方式，获得用于测定确定的三环抗抑郁药物样品，其不含干扰代谢物。

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