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1. 发明授权

US06225493B1 Metal ion assisted N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester isomer resolution 有权
标题翻译：金属离子辅助的N- [N-（3,3-二甲基丁基）-L-α-天冬氨酰基] -L-苯丙氨酸1-甲酯异构体拆分
公开(公告)号：US06225493B1
公开(公告)日：2001-05-01
申请号：US09641976
申请日：2000-08-21
申请人： Indra Prakash , Joseph P. Haar, Jr. , Robert Y. Zhao
发明人： Indra Prakash , Joseph P. Haar, Jr. , Robert Y. Zhao
IPC分类号： C07C22900
CPC分类号： C07K5/06113
摘要： This invention relates to the purification of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester by resolving a mixture of the alpha- and beta-isomers of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester using metal ions.
摘要翻译：本发明涉及通过将N- [N-（3,3-二甲基丁基）-L-α-天冬氨酰基] -L-苯丙氨酸1-甲酯的α-和β-异构体的混合物拆分，使用金属离子的N-（3,3-二甲基丁基）-L-α-天冬氨酰基] -L-苯丙氨酸1-甲基酯。

2. 发明授权

US08383649B2 Crystalline forms of naltrexone methobromide 有权
标题翻译：纳曲酮甲溴化氢的结晶形式
公开(公告)号：US08383649B2
公开(公告)日：2013-02-26
申请号：US12668218
申请日：2008-06-25
申请人： Gary A. Nichols , Robert E. Halvachs , Gary L. Cantrell , Kevin R. Roesch , Joseph P. Haar, Jr.
发明人： Gary A. Nichols , Robert E. Halvachs , Gary L. Cantrell , Kevin R. Roesch , Joseph P. Haar, Jr.
IPC分类号： A01N43/40 , A01N43/02 , A01N43/08 , A61K31/445 , A61K31/335 , A61K31/34
CPC分类号： C07D489/08 , C07D489/04
摘要： The present invention relates to novel crystalline forms of naltrexone methobromide including hydrated and solvated forms. The invention also describes methods of preparing the various crystalline forms. The present invention also relates to pharmaceutical compositions containing crystalline forms of naltrexone methobromide, as well as methods of treating or preventing opioid induced side effects by administering the pharmaceutical compositions.
摘要翻译：本发明涉及包含水合和溶剂化形式的纳曲酮甲基溴化物的新型结晶形式。本发明还描述了制备各种结晶形式的方法。本发明还涉及包含结晶形式的纳曲酮甲溴化物的药物组合物，以及通过施用药物组合物来治疗或预防阿片样物质诱导的副作用的方法。

3. 发明授权

US08669366B2 Process for the preparation of quaternary N-alkyl morphinan alkaloid salts 有权
标题翻译：制备季铵N-烷基吗啡喃生物碱盐的方法
公开(公告)号：US08669366B2
公开(公告)日：2014-03-11
申请号：US12529723
申请日：2008-03-06
申请人： Peter X. Wang , Gary L. Cantrell , Robert E. Halvachs , Kevin R. Roesch , Henry J. Buehler , Joseph P. Haar, Jr.
发明人： Peter X. Wang , Gary L. Cantrell , Robert E. Halvachs , Kevin R. Roesch , Henry J. Buehler , Joseph P. Haar, Jr.
IPC分类号： C07D471/00
CPC分类号： C07D489/08 , C07D489/02 , C07D489/04 , Y02P20/582
摘要： An improved process for the N-alkylation of tertiary morphinan alkaloid bases to form the corresponding quaternary morphinan alkaloid derivatives.
摘要翻译：一种改进的草甘膦生物碱碱基N-烷基化方法，形成相应的季吗啡生物碱衍生物。

4. 发明授权

US08283472B2 Synthesis of methylphenidate and analogs thereof 有权
标题翻译：哌甲酯及其类似物的合成
公开(公告)号：US08283472B2
公开(公告)日：2012-10-09
申请号：US12652894
申请日：2010-01-06
申请人： Joseph P. Haar, Jr. , Carl J. Schaefer , Charles S. Kuivila
发明人： Joseph P. Haar, Jr. , Carl J. Schaefer , Charles S. Kuivila
IPC分类号： C07D211/34
CPC分类号： C07D211/60
摘要： A synthetic process for the preparation of amino acid esters such as methylphenidate and analogs thereof is disclosed. The process involves reacting an amino acid such as α-phenyl-α-(2-piperidinyl)acetic acid or an analog thereof with an alcohol such as methanol in the presence of an acid and a water sequestrant such as trimethyl orthoacetate. In some embodiments, the water sequestrant is added to the reaction mixture after an initial period of esterification and then the reaction is allowed to continue. The α-phenyl-α-(2-piperidinyl)acetic acid methyl ester or analog thereof is then isolated from the reaction mixture. In one variation of the process, the supernatant liquid may be recycled in subsequent runs to increase yield and product purity.
摘要翻译：公开了用于制备氨基酸酯如哌甲酯及其类似物的合成方法。该方法包括在酸和水多价螯合剂如原乙酸三甲酯存在下使氨基酸如α-苯基-α-（2-哌啶基）乙酸或其类似物与醇如甲醇反应。在一些实施方案中，在酯化的初始阶段之后，将水螯合剂加入到反应混合物中，然后使反应继续进行。然后从反应混合物中分离α-苯基-α-（2-哌啶基）乙酸甲酯或其类似物。在该方法的一个变化方案中，上清液可以在随后的运行中再循环以提高产率和产物纯度。

5. 发明授权

US5998491A Super-absorbing polymeric networks 失效
标题翻译：超吸收聚合物网络
公开(公告)号：US5998491A
公开(公告)日：1999-12-07
申请号：US014066
申请日：1998-01-27
申请人： Joseph P. Haar, Jr.
发明人： Joseph P. Haar, Jr.
IPC分类号： C08G69/48 , C08G73/10 , C07D243/00 , C08J9/36
CPC分类号： C08G73/1092
摘要： Super-absorbing polymeric networks of crosslinked polyaspartates are produced from crosslinked polysuccinimide. Super-absorbing polymeric networks are produced in a single reaction vessel by crosslinking polysuccinimide with at least one organic polyamine crosslinking agent in the presence of at least one nitrogenous base. The reaction is carried out in an aqueous reaction mixture to produce a polymeric network of crosslinked polyaspartate.
摘要翻译：交联聚天冬氨酸酯的超吸收聚合物网络由交联聚琥珀酰亚胺制备。通过在至少一个含氮碱的存在下使聚琥珀酰亚胺与至少一种有机多胺交联剂交联，在单个反应容器中制备超吸收聚合物网络。该反应在水性反应混合物中进行以产生交联聚天冬氨酸酯的聚合物网络。

6. 发明授权

US08946433B2 Process for the preparation of sufentanil base and related compounds 有权
标题翻译：制备舒芬太尼碱及相关化合物的方法
公开(公告)号：US08946433B2
公开(公告)日：2015-02-03
申请号：US13233227
申请日：2011-09-15
申请人： Brian Orr , Joseph P. Haar, Jr. , George H. Klemm , Keith G. Tomazi
发明人： Brian Orr , Joseph P. Haar, Jr. , George H. Klemm , Keith G. Tomazi
IPC分类号： C07D409/06 , C07D211/58
CPC分类号： C07D409/06
摘要： The present disclosure generally related to an improved process for the preparation of various piperidine derivatives. More particularly, the present disclosure related to an improved process for preparing sufentanil base (1) and related compounds, which advantageously utilizes more cost effective and/or less hazardous reagents, including a dispersion comprising between about 50% and about 70% by weight (based on the total weight of the dispersion) of an alkali metal hydride, such as sodium hydride, as well as eliminates the need for expensive and/or time consuming purification techniques.
摘要翻译：本公开通常涉及用于制备各种哌啶衍生物的改进方法。更具体地说，本发明涉及一种制备舒芬太尼碱（1）和相关化合物的改进方法，其有利地利用更具成本效益和/或更不危险的试剂，包括包含约50重量％至约70重量％基于分散体的总重量）碱金属氢化物如氢化钠，并且不需要昂贵和/或耗时的纯化技术。

7. 发明授权

US5998492A Super-absorbing polymeric networks 有权
标题翻译：超吸收聚合物网络
公开(公告)号：US5998492A
公开(公告)日：1999-12-07
申请号：US178963
申请日：1998-10-26
申请人： Joseph P. Haar, Jr. , Robert J. Ross
发明人： Joseph P. Haar, Jr. , Robert J. Ross
IPC分类号： A61L15/60 , C08G73/10 , C08J9/28
CPC分类号： C08J9/28 , A61L15/60 , C08G73/1092 , C08J2377/04
摘要： Disclosed are methods of producing super-absorbing polymeric networks of polyaspartates from crosslinked polysuccinimide. In one preferred aspect, polysuccinimide is first reacted with an organic crosslinking agent, preferably an organic base containing at least two primary amine groups, to form a gelled crosslinked polysuccinimide. The gelled crosslinked polysuccinimide is then base hydrolyzed to a gelled polymeric network of polyaspartate and deswollen with at least one liquid alcohol to a polymeric network of polyaspartate which demonstrates super-absorbing capability in water and in electrolyte solution. Super-absorbing polymeric networks of polyaspartates can also be produced in a single reaction vessel by sequentially crosslinking a polysuccinimide with an organic crosslinking agent in an aqueous reaction medium, optionally containing a mineral acid, and then hydrolyzing the crosslinked polysuccinimide to produce a polymeric network of polyaspartate.
摘要翻译：公开了从交联聚琥珀酰亚胺生产聚天冬氨酸的超吸收聚合物网络的方法。在一个优选的方面，首先将聚琥珀酰亚胺与有机交联剂，优选含有至少两个伯胺基团的有机碱反应，以形成凝胶状交联的聚琥珀酰亚胺。然后将凝胶状交联的聚琥珀酰亚胺碱基水解成聚天冬氨酸的凝胶聚合物网络，并用至少一种液态醇解聚到聚天冬氨酸的聚合物网络，其在水和电解质溶液中表现出超吸收能力。聚天冬氨酸的超吸收聚合物网络也可以通过在含水无机酸的水性反应介质中依次使聚琥珀酰亚胺与有机交联剂交联，然后水解交联聚琥珀酰亚胺以产生聚聚天冬氨酸

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