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    • 3. 发明申请
    • Compositions of Allosteric Hemoglobin Modifiers and Methods of Making the Same
    • 变构血红蛋白改性剂的组成及其制备方法
    • US20070293698A1
    • 2007-12-20
    • US10598874
    • 2005-04-22
    • Al QuickAntonio SantosAlexandre J.G. CarvalhoDouglas JohnsonJeffrey EtterChris Murray
    • Al QuickAntonio SantosAlexandre J.G. CarvalhoDouglas JohnsonJeffrey EtterChris Murray
    • C07C233/01C07C231/00G01N30/00C07C233/00
    • A61K31/195
    • The present invention provides novel compositions of allosteric hemoglobin modifiers which are substantially free of impurities, specifically polymeric impurities. In one embodiment, the novel compositions contain an allosteric hemoglobin modifier compound and less than 100 ppm of the polymeric impurities generated during the preparation of this compound. Included in the present invention are novel methods for preparing allosteric hemoglobin modifiers that are substantially free of polymeric impurities. Also included in the present invention are improved methods for the purification of the product formed by the method of this invention. The novel methods of purification comprise extracting the crude composition with a water immiscible or partially immiscible solvent such as methylisobutyl ketone (MIBK) to lower amounts of impurities, specifically polymeric impurities. Also included are methods to reduce impurities by recrystallization of the crude synthesized product, followed by filtration of the recrystallized product. The present invention also includes the products made by the processes of the invention and methods for analyzing compositions comprised of these products.
    • 本发明提供基本上不含杂质,特别是聚合物杂质的变构血红蛋白改性剂的新型组合物。 在一个实施方案中,新型组合物含有变构血红蛋白改性剂化合物,并且在制备该化合物期间产生小于100ppm的聚合物杂质。 本发明包括制备基本上不含聚合物杂质的变构型血红蛋白改性剂的新方法。 本发明还包括用于纯化通过本发明方法形成的产品的改进方法。 新颖的纯化方法包括用与水不混溶或部分不混溶的溶剂如甲基异丁基酮(MIBK)提取粗组合物以降低杂质量,特别是聚合物杂质。 还包括通过粗合成产物的重结晶减少杂质的方法,然后过滤重结晶产物。 本发明还包括通过本发明的方法制备的产品和用于分析由这些产品组成的组合物的方法。
    • 4. 发明申请
    • Preparation and Use of a Stable Formulation of Allosteric Effector Compounds
    • 稳定配方的变构效应剂的制备和应用
    • US20070212302A1
    • 2007-09-13
    • US11749610
    • 2007-05-16
    • Douglas JohnsonMark DotyJames Kipp
    • Douglas JohnsonMark DotyJames Kipp
    • A61K31/205A61B5/055
    • A61K31/195A61K9/0019A61K47/12A61K47/18A61K47/183A61K49/10
    • A pharmaceutical composition of 2-[4-[2-[(3,5-dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2-methyl-propionic acid or its physiologically acceptable salts suitable for parenteral administration includes an aqueous formulation of 2-[4-[2-[(3,5-dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2-methyl-propionic acid or its physiologically acceptable salt and a buffer to maintain the pH from about 6 to about 11. The composition in accordance with the invention reduces the amount of particulate matter that forms in solution after heat sterilization. The invention also includes a process for making a pharmaceutical composition of 2-[4-[2-[(3,5-dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2-methyl-propionic acid or its physiologically acceptable salt that has a shelf life in excess of thirty days and is useful in parenteral administration.
    • 2- [4- [2 - [(3,5-二甲基苯基)氨基] -2-氧代乙基]苯氧基] -2-甲基 - 丙酸或其适用于胃肠外给药的生理学上可接受的盐的药物组合物包括 2- [4- [2 - [(3,5-二甲基苯基)氨基] -2-氧代乙基]苯氧基] -2-甲基 - 丙酸或其生理上可接受的盐和缓冲液,以将pH保持在约6至约11 根据本发明的组合物减少加热灭菌后在溶液中形成的颗粒物质的量。 本发明还包括制备2- [4- [2 - [(3,5-二甲基苯基)氨基] -2-氧代乙基]苯氧基] -2-甲基 - 丙酸或其生理上可接受的盐的药物组合物的方法, 保质期超过30天,可用于肠胃外给药。
    • 5. 发明申请
    • Mixed frequency amplitude-based servo pattern
    • 混合频率幅度伺服模式
    • US20070002487A1
    • 2007-01-04
    • US11171958
    • 2005-06-29
    • Denis LangloisDouglas Johnson
    • Denis LangloisDouglas Johnson
    • G11B5/584
    • G11B5/584
    • The invention is directed to a servo frame that includes servo windows written with different frequencies to provide redundant positioning information. The servo frame includes a set of first servo windows recorded at a first frequency and a set of second servo windows recorded at a second frequency arranged in a checkerboard-like pattern. The different frequencies of the servo windows allow the servo frame to achieve improved positioning information redundancy. A servo track may include a plurality of the servo frames described herein to accurately position data read/write heads adjacent corresponding data tracks. The redundancy built into each of the servo frames substantially minimizes errors in the positioning information.
    • 本发明涉及一种包括以不同频率写入的伺服窗口以提供冗余定位信息的伺服帧。 伺服帧包括以第一频率记录的一组第一伺服窗口和以棋盘状图案布置的以第二频率记录的一组第二伺服窗口。 伺服窗口的不同频率允许伺服框架实现改进的定位信息冗余。 伺服轨道可以包括本文描述的多个伺服帧,以将数据读/写头精确地定位在相邻的数据轨道附近。 内置在每个伺服帧中的冗余基本上使定位信息中的错误最小化。
    • 7. 发明申请
    • Compositions of allosteric hemoglobin modifiers and methods of making the same
    • 变构血红蛋白修饰剂的组成及其制备方法
    • US20050239893A1
    • 2005-10-27
    • US11112389
    • 2005-04-22
    • Al QuickAntonio SantosAlexandre CarvalhoDouglas JohnsonJeffrey EtterChristopher Murray
    • Al QuickAntonio SantosAlexandre CarvalhoDouglas JohnsonJeffrey EtterChristopher Murray
    • A61K31/195
    • A61K31/195
    • The present invention provides novel compositions of allosteric hemoglobin modifiers which are substantially free of impurities, specifically polymeric impurities. In one embodiment, the novel compositions contain an allosteric hemoglobin modifier compound and less than 100 ppm of the polymeric impurities generated during the preparation of this compound. Included in the present invention are novel methods for preparing allosteric hemoglobin modifiers that are substantially free of polymeric impurities. Also included in the present invention are improved methods for the purification of the product formed by the method of this invention. The novel methods of purification comprise extracting the crude composition with a water immiscible or partially immiscible solvent such as methylisobutyl ketone (MIBK) to lower amounts of impurities, specifically polymeric impurities. Also included are methods to reduce impurities by recrystallization of the crude synthesized product, followed by filtration of the recrystallized product. The present invention also includes the products made by the processes of the invention and methods for analyzing compositions comprised of these products.
    • 本发明提供基本上不含杂质,特别是聚合物杂质的变构血红蛋白改性剂的新型组合物。 在一个实施方案中,新型组合物含有变构血红蛋白改性剂化合物,并且在制备该化合物期间产生小于100ppm的聚合物杂质。 本发明包括制备基本上不含聚合物杂质的变构型血红蛋白改性剂的新方法。 本发明还包括用于纯化通过本发明方法形成的产品的改进方法。 新的纯化方法包括用与水不混溶或部分不混溶的溶剂如甲基异丁基酮(MIBK)萃取粗组合物以降低杂质量,特别是聚合物杂质。 还包括通过粗合成产物的重结晶减少杂质的方法,然后过滤重结晶产物。 本发明还包括通过本发明的方法制备的产品和用于分析由这些产品组成的组合物的方法。