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1. 发明授权

US06506767B1 8-chloro-6,11-dihydro-11-(4-piperidylidine)-5H-benzo[5,6]cyclohepta[1-2-b] pyridine 失效
标题翻译： 8-氯-6,11-二氢-11-（4-哌啶基）-5H-苯并[5,6]环庚并[1-2-b]吡啶
公开(公告)号：US06506767B1
公开(公告)日：2003-01-14
申请号：US09108689
申请日：1998-07-01
申请人： Doris P. Schumacher , Junning Lee , Lawrence R. Rogers , Charles G. Eckhart , Naneshwar S. Sawant , Michael B. Mitchell
发明人： Doris P. Schumacher , Junning Lee , Lawrence R. Rogers , Charles G. Eckhart , Naneshwar S. Sawant , Michael B. Mitchell
IPC分类号： C07D40108
CPC分类号： C07D401/04
摘要： Crystalline polymorphs of 8-chloro-6,11-dihydro-11-(4-piperidylidene)-5H-benzo[5,6]cycloheptic[1,2-b]pyridine represented by the formula pharmaceutical compositions containing such polymorphs, and methods of using such polymorphs to treat allergic reactions in mammals such as man are disclosed.
摘要翻译：由含有这种多晶型物的药物组合物表示的8-氯-6,11-二氢-11-（4-哌啶基）-5H-苯并[5,6]环庚并[1,2-b]吡啶的结晶多晶型物，以及公开了使用这种多晶型物来治疗哺乳动物如人的过敏反应

2. 发明授权

US06623760B1 Method of preparing particles for agglomeration 有权
标题翻译：制备团聚颗粒的方法
公开(公告)号：US06623760B1
公开(公告)日：2003-09-23
申请号：US09490796
申请日：2000-01-26
申请人： Tsong-Toh Yang , Stephen K. C. Yu , Charles G. Eckhart , Michael B. Mitchell
发明人： Tsong-Toh Yang , Stephen K. C. Yu , Charles G. Eckhart , Michael B. Mitchell
IPC分类号： A61K914
CPC分类号： A61K9/145 , A61K31/167 , A61K31/58
摘要： Methods of preparing particulates for agglomeration, having a specified particle size distribution and desired convertible amorphous content, are described. The method involves a plurality of micronizing steps at least two of which are separated by a curing step. In the curing step, a stimulus such as humidity may be used to crystallize at least some, and in many instances preferably all, of the convertible amorphous content.
摘要翻译：描述了制备具有特定粒度分布和所需可转化非晶体含量的附聚颗粒的方法。该方法涉及多个微粉化步骤，其中至少两个通过固化步骤分离。在固化步骤中，可以使用诸如湿度的刺激来使至少一些，并且在许多情况下优选全部可结晶的无定形含量。

3. 发明授权

US4634556A Crystalline sodium (5R, 6S, 8R)-6-(1-hydroxyethyl)-2-(2-carbamoyloxyethylthio)-penem-3-carboxylate and process for making same 失效
标题翻译：结晶钠（5R，6S，8R）-6-（1-羟乙基）-2-（2-氨基甲酰氧基乙硫基） - 庚-3-烯酸甲酯及其制备方法
公开(公告)号：US4634556A
公开(公告)日：1987-01-06
申请号：US732533
申请日：1985-05-10
申请人： John K. Jenkins , John S. Chiu , Charles G. Eckhart , Paul E. McNamara , Stanley Rosenhouse , Richard E. Youngstrom
发明人： John K. Jenkins , John S. Chiu , Charles G. Eckhart , Paul E. McNamara , Stanley Rosenhouse , Richard E. Youngstrom
IPC分类号： C07D499/88 , C07D499/00 , A61K31/425
CPC分类号： C07D499/88
摘要： A novel, stable, crystalline sodium (5R,6S,8R)-6-(1-hydroxyethyl)-2-(2-carbamoyloxyethylthio)-penem-3-carboxylate (designated as Form II) is prepared by forming a homogenous solution of sodium (5R,6S,8R)-6-(1-hydroxyethyl)-2-(2-carbamoyloxyethylthio)-penem-3-carboxylate combined with stirring the homogenous solution for a time and at a temperature sufficient to produce Form II and recovering Form II. Form II may also be prepared by contacting a first solution obtained by dissolving (5R,6S,8R)-6-(1-hydroxyethyl)-2-(2-carbamoyloxyethylthio)-penem-3-carboxylic acid in dimethylacetamide with a second solution obtained by dissolving a sodium salt of an organic acid having a pKa of up to about 5, e.g., sodium 2-ethylhexanoate in acetone, in the presence of at least 5 volume percent water while stirring the reaction mixture so formed at a temperature and for a time sufficient to produce Form II followed by recovering Form II.Form II exhibits a greater physical stability and increased solid state chemical stability and reduced hygroscopicity over that of the amorphous form (e.g., Form I) which renders Form II greatly superior to Form I as a clinically suitable antibacterial agent.
摘要翻译：通过形成均匀的溶液来制备新的稳定的结晶的（5R，6S，8R）-6-（1-羟乙基）-2-（2-氨基甲酰氧基乙硫基） - 庚-3-烯氧基化钠（命名为II型）的（5R，6S，8R）-6-（1-羟乙基）-2-（2-氨基甲酰氧基乙硫基） - 庚-3-烯酰氧基化合物与搅拌均匀溶液一段时间并在足以产生II型并恢复II型。形式II也可以通过将通过将（5R，6S，8R）-6-（1-羟乙基）-2-（2-氨基甲酰氧基乙硫基） - 亚氨基-3-碳氧基酸溶解在二甲基乙酰胺中获得的第一溶液与第二溶液通过在至少5体积％的水的存在下，将具有高达约5的pKa的有机酸的钠盐例如2-乙基己酸酯溶解在丙酮中而获得的溶液，同时搅拌在温度下形成的反应混合物，一段时间足以生产II型，然后恢复II型。 II型具有更大的物理稳定性和增加的固态化学稳定性，并且比非晶形式（例如，形式I）的吸湿性降低，其使得II型作为临床合适的抗菌剂大大优于I型。

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