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71. 发明授权

US09066848B2 Process for making sterile aripiprazole of desired mean particle size 有权
标题翻译：制备所需平均粒径的无菌阿立哌唑的方法
公开(公告)号：US09066848B2
公开(公告)日：2015-06-30
申请号：US13771691
申请日：2013-02-20
申请人： Bristol-Myers Squibb Company
发明人： Margaret M. Gleeson , Soojin Kim , Donald C. Kientzler , San Kiang
IPC分类号： A61J3/02 , C07D215/227 , B01D9/00 , B01J2/06
CPC分类号： A61J3/02 , B01D9/0009 , B01D9/005 , B01D9/0054 , B01D9/0063 , B01D9/0081 , B01J2/06 , C07D215/227
摘要： A process is provided for making sterile aripiprazole having an average particle size less than 100 microns but preferably greater than 25 microns employing an impinging jet crystallization procedure. The resulting bulk aripiprazole of desired particle size may be used to form a sterile freeze-dried aripiprazole formulation, which upon constitution with water and intramuscular injection releases aripiprazole over a period of at least about one week and up to about eight weeks.
摘要翻译：提供了一种制备平均粒径小于100微米但优选大于25微米的无菌阿立哌唑的方法，其采用冲击射流结晶方法。所得粒度的阿立哌唑可用于形成无菌冷冻干燥的阿立哌唑制剂，其在用水和肌内注射后，在至少约一周至多达八周的时间内释放阿立哌唑。

72. 发明申请

US20130305558A1 APPARATUS AND PROCESS FOR CONCENTRATING A SEPARABLE COMPONENT OF A SLURRY 有权
标题翻译：用于浓缩浆料分离成分的装置和方法
公开(公告)号：US20130305558A1
公开(公告)日：2013-11-21
申请号：US13896627
申请日：2013-05-17
申请人： Margalit Mogilevsky
发明人： MIKHAIL (MICHAEL) MOGILEVSKY
IPC分类号： F26B5/00
CPC分类号： F26B5/00 , B01D9/0081 , B01D9/04 , B01D33/0338 , C02F1/22 , C02F11/12
摘要： Methods and apparatuses are provided for separating a slurry mixture into its constituent melted liquid form and solid frozen form. This involves forcing the slurry mixture through an inlet into a vessel and through the vessel to an opening, wherein the vessel comprises a plurality of perforations dimensioned to receive a liquid flow from the slurry mixture to dry the slurry mixture; vibrating the vessel and the slurry mixture within the vessel to shake the material in the melted liquid form out through the plurality of perforations to dry the slurry mixture; and, extracting the dried slurry mixture from the opening.
摘要翻译：提供了用于将浆料混合物分离成其组分熔融液体形式和固体冷冻形式的方法和装置。这涉及迫使浆料混合物通过入口进入容器并通过容器到达开口，其中容器包括多个穿孔，其尺寸被设计成接收来自浆料混合物的液体流以干燥浆料混合物; 在容器内振动容器和浆料混合物，以通过多个穿孔将熔融液体中的材料形成振荡，以干燥浆料混合物; 并从开口中提取干燥的浆料混合物。

73. 发明申请

US20130299099A1 TARGET SUBSTANCE TRANSFER METHOD, CRYSTAL PRODUCTION METHOD, COMPOSITION PRODUCTION METHOD, AND TARGET SUBSTANCE TRANSFER DEVICE 有权
标题翻译：目标物质转移方法，晶体生产方法，组合物生产方法和目标物质转移装置
公开(公告)号：US20130299099A1
公开(公告)日：2013-11-14
申请号：US13980212
申请日：2012-01-18
申请人： Yusuke Mori , Tsuyoshi Inoue , Kazufumi Takano , Hiroyoshi Matsumura , Hiroaki Adachi , Shigeru Sugiyama , Ryota Murai , Masateru Kurata , Hiroshi Yoshikawa , Mihoko Hirao , Satoshi Nakayama , Yoshinori Takahashi , Satoshi Murakami
发明人： Yusuke Mori , Tsuyoshi Inoue , Kazufumi Takano , Hiroyoshi Matsumura , Hiroaki Adachi , Shigeru Sugiyama , Ryota Murai , Masateru Kurata , Hiroshi Yoshikawa , Mihoko Hirao , Satoshi Nakayama , Yoshinori Takahashi , Satoshi Murakami
IPC分类号： B01J19/00
CPC分类号： B01J19/008 , B01D9/0081 , B01J19/10 , B01J19/121 , C30B5/00 , C30B29/58
摘要： The present invention provides a target substance transfer method, a crystal production method, a composition production method, and a target substance transfer device, which allow the concentration of a target substance to be increased easily and effectively. The target substance transfer method is a method for transferring a target substance 103 from a first phase 101 that is a liquid or solid phase containing the target substance 103 to a second phase 102 including: a phase approximation step of bringing the first phase 101 and the second phase 102 into close proximity; and a bubble collapse step of forming bubbles in the vicinity of a boundary between the first phase 101 and the second phase 102 and then causing the bubbles to collapse.
摘要翻译：本发明提供了能够容易且有效地增加目标物质浓度的目标物质转移方法，结晶生产方法，组合物制备方法和目标物质转移装置。目标物质转移方法是从包含目标物质103的液相或固相的第一相101向第二相102输送目标物质103的方法，包括：使第一相101和第二阶段102接近; 以及在第一相101和第二相102之间的边界附近形成气泡，然后使气泡塌陷的气泡塌陷步骤。

74. 发明申请

US20100190760A1 Process for Making Crystals 有权
标题翻译：制作晶体的过程
公开(公告)号：US20100190760A1
公开(公告)日：2010-07-29
申请号：US12665019
申请日：2008-06-17
申请人： Graham Ruecroft , James Robinson , Dipesh Parikh
发明人： Graham Ruecroft , James Robinson , Dipesh Parikh
IPC分类号： A61K9/10 , A61K31/19 , A61K31/56 , B01F11/02 , A61K9/107
CPC分类号： B01J2/06 , A61K9/0073 , A61K9/14 , B01D9/0009 , B01D9/0018 , B01D9/005 , B01D9/0054 , B01D9/0059 , B01D9/0081 , B01J2/18
摘要： A process for preparing an emulsion or a dispersion comprising crystalline particles of at least one active principal that comprises contacting a solution of at least one solute in a solvent or mixture of solvents in a first flowing stream with a non-solvent in a second flowing stream wherein the non-solvent and solvent are not miscible with each other, so as to form an emulsion or a dispersion. Super saturation is brought about by suitable means, and the emulsion or dispersion is subjected to ultrasonic irradiation to mediate crystal nucleation.
摘要翻译：一种制备包含至少一种活性主体的结晶颗粒的乳液或分散体的方法，包括使第一流动中的溶剂或溶剂混合物中的至少一种溶质的溶液与第二流动流中的非溶剂接触其中所述非溶剂和溶剂彼此不混溶，以形成乳液或分散体。通过合适的方法产生超饱和，并且对乳液或分散体进行超声波照射以介导晶体成核。

75. 发明申请

US20090306339A1 Preparation of Fine Particles 审中-公开
标题翻译：微粒的制备
公开(公告)号：US20090306339A1
公开(公告)日：2009-12-10
申请号：US12441943
申请日：2007-07-20
申请人： Huibert Albertus Van Boxtel
发明人： Huibert Albertus Van Boxtel
IPC分类号： A61K38/13 , C07D305/14 , C07C69/76
CPC分类号： B01D9/0054 , A61K9/1694 , A61K9/5146 , A61K9/5192 , B01D9/0081 , B01F7/16 , B01F7/26 , B01F13/0827 , Y10T428/2982
摘要： A process for the precipitation of an organic compound comprising mixing simultaneously introduced streams of a solution and a precipitation agent in a chamber using a mechanical stirrer in the presence of an amphiphilic polymer. The process may be operated in a continuous manner and is particularly useful for providing low solubility organic compounds (e.g. pharmaceuticals) in readily dispersible, nano-sized particulate form up to manufacturing scale.
摘要翻译：一种沉淀有机化合物的方法，包括在两亲性聚合物存在下，使用机械搅拌器在室内同时引入溶液和沉淀剂流。该方法可以以连续方式操作，并且特别可用于提供直至制造规模的容易分散的纳米尺寸颗粒形式的低溶解度有机化合物（例如药物）。

76. 发明申请

US20070065372A1 Process for the production of particles 审中-公开
标题翻译：颗粒生产工艺
公开(公告)号：US20070065372A1
公开(公告)日：2007-03-22
申请号：US10546433
申请日：2004-02-19
申请人： Robert Price , Joerg Kaerger
发明人： Robert Price , Joerg Kaerger
IPC分类号： A61K9/14
CPC分类号： A61K9/1688 , A61K9/0073 , A61K31/137 , A61K31/167 , A61K31/573 , A61K31/58 , B01D9/0027 , B01D9/005 , B01D9/0081 , C30B7/00 , C30B29/54
摘要： A process for the production of particles comprises the steps of formation of a solution of a desired substance in a suitable solvent; ii)generation of an aerosol from the solution of said substance; iii) collection of the aerosol droplets in a vessel containing a non-solvent of said substance; and iv) application of ultrasound to the droplets dispersed in the non-solvent to effect crystallisation of said substance. The particles produced find application in for example pharmaceutical and agrochemical formulations, especially in inhalation formulations.
摘要翻译：制备颗粒的方法包括在合适的溶剂中形成所需物质的溶液的步骤; ii）从所述物质的溶液中产生气溶胶; iii）将烟雾液滴收集在含有所述物质的非溶剂的容器中; 以及iv）对分散在非溶剂中的液滴施加超声波以实现所述物质的结晶。产生的颗粒可用于例如药物和农药制剂，特别是在吸入制剂中。

77. 发明授权

US07122083B2 Apparatus and process used in growing crystals 有权
标题翻译：用于生长晶体的装置和工艺
公开(公告)号：US07122083B2
公开(公告)日：2006-10-17
申请号：US10405436
申请日：2003-04-02
申请人： Daniel Albert Green
发明人： Daniel Albert Green
IPC分类号： C30B7/08
CPC分类号： B82Y30/00 , B01D9/0013 , B01D9/0018 , B01D9/005 , B01D9/0081 , C30B7/00 , C30B29/54
摘要： This invention relates to a novel system for making uniform crystals. The system, by virtue of the nature of its crystal product, is useful in various chemical, pharmaceutical, agricultural, and biotechnology applications. The invention features physically separated and controlled crystal nucleation and growth zones useful in industrially scaled crystallization processes. The invention also provides a method to preferentially nucleate and crystallize a desired category of crystal structure (enantiomer, solvate, polymorph) of non-chiral and chiral compounds.
摘要翻译：本发明涉及一种制备均匀晶体的新系统。该系统凭借其晶体产品的性质，可用于各种化学，制药，农业和生物技术应用。本发明具有物理分离和控制的晶体成核和生长区域，其可用于工业规模结晶过程。本发明还提供了优选使非手性和手性化合物的所需类型的晶体结构（对映异构体，溶剂合物，多晶型物）成核并结晶的方法。

78. 发明授权

US06960256B2 Formation of small crystals 失效
标题翻译：形成小晶体
公开(公告)号：US06960256B2
公开(公告)日：2005-11-01
申请号：US10476156
申请日：2002-05-02
申请人： Michael Joseph Bowe , John William Stairmand , Linda Jane McCausland
发明人： Michael Joseph Bowe , John William Stairmand , Linda Jane McCausland
IPC分类号： A61K9/14 , A61K9/16 , A61K31/43 , B01D9/00 , B01D9/02 , B01F5/00 , B01F11/02 , B01F13/10 , C30B7/00 , C30B7/08
CPC分类号： C30B7/00 , A61K9/1688 , B01D9/0027 , B01D9/005 , B01D9/0059 , B01D9/0081 , B01F5/0057 , B01F11/0258 , B01F11/0266 , B01F13/1025
摘要： Small crystals are made by mixing a solution of a desired substance with an anti-solvent in a fluidic vortex mixer in which the residence time is less than 1 s, for example 10 ms. The liquid within the fluidic vortex mixer (12) is subjected to high intensity ultrasound from a transducer (20, 22) in or on the wall of the mixer, or coupled to a pipe supplying liquid to the mixer. The solution very rapidly becomes supersaturated, and the ultrasound can induce a very large number of nuclei for crystal growth. Small crystals, for example less than 5 μm, are formed that may be of a suitable size for use in inhalers.
摘要翻译：通过将所需物质与抗溶剂的溶液在其中停留时间小于1秒，例如10ms的流体涡旋混合器中混合来制备小晶体。流体涡流混合器（12）内的液体经受来自混合器壁上或其上的换能器（20,22）的高强度超声波，或耦合到向混合器供应液体的管道。溶液非常迅速地变得过饱和，并且超声可以诱导非常大量的用于晶体生长的核。形成小晶体，例如小于5μm，其可以具有适合用于吸入器的尺寸。

79. 发明申请

US20050188913A1 Production of crystalline materials by using high intensity ultrasound 有权
标题翻译：通过使用高强度超声波生产结晶材料
公开(公告)号：US20050188913A1
公开(公告)日：2005-09-01
申请号：US10514883
申请日：2003-05-13
申请人： Linda McCausland , John Perkins
发明人： Linda McCausland , John Perkins
IPC分类号： C07H3/02 , B01D9/00 , B01D9/02 , C07K5/072 , C30B1/00
CPC分类号： B01D9/0013 , B01D9/0036 , B01D9/0063 , B01D9/0081 , C07K5/0613 , Y10T117/1024 , Y10T117/1028
摘要： A crystalline material sufficiently pure for use in pharmaceuticals may be made by forming a saturated solution of the material, changing the temperature of the solution so it becomes supersaturated, and subjecting the solution to irradiation by high intensity ultrasound, the frequency of the ultrasound being scanned over a range of frequencies. For example the ultrasound may be varied between 19.5 and 20.5 kHz, and this variation may be sinusoidal. Preferably the ultrasound is provided only briefly, say for less than 5 s, before allowing the solution to cool gradually without further irradiation. The ultrasound may be applied using a vessel with an array of ultrasonic transducers attached to a wall, so each transducer radiates no more than 3 W/cm2 yet the power dissipation within the vessel is between 25 and 150 W/litre. This method can reduce the metastable zone width to less than 10 K. It is applicable in particular to aspartame.
摘要翻译：可以通过形成饱和的材料溶液，改变溶液的温度，使其变得过饱和，并通过高强度超声波对该溶液进行照射，使超声频率被扫描，可以制备足够纯的用于药物的结晶物质在一个频率范围内。例如，超声可以在19.5和20.5kHz之间变化，并且该变化可以是正弦的。优选地，在允许溶液逐渐冷却而不进一步照射之前，仅提供超声波，例如少于5秒。可以使用具有附接到壁的超声波换能器阵列的血管来应用超声波，因此每个换能器辐射不超过3W / cm 2，但是容器内的功率耗散在25和150之间 W /升。该方法可将亚稳区宽度减小到10K以下。特别适用于阿斯巴甜。

80. 发明申请

US20050152981A1 Process for making sterile aripiprazole of desired mean particle size 审中-公开
标题翻译：制备所需平均粒径的无菌阿立哌唑的方法
公开(公告)号：US20050152981A1
公开(公告)日：2005-07-14
申请号：US10968481
申请日：2004-10-19
申请人： Margaret Gleeson , Soojin Kim , Donald Kientzler , San Kiang
发明人： Margaret Gleeson , Soojin Kim , Donald Kientzler , San Kiang
IPC分类号： B01D9/00 , C07D215/22 , C07D215/227 , A61K9/14
CPC分类号： A61J3/02 , B01D9/0009 , B01D9/005 , B01D9/0054 , B01D9/0063 , B01D9/0081 , B01J2/06 , C07D215/227
摘要： A process is provided for making sterile aripiprazole having an average particle size less than 100 microns but preferably greater than 25 microns employing an impinging jet crystallization procedure. The resulting bulk aripiprazole of desired particle size may be used to form a sterile freeze-dried aripiprazole formulation, which upon constitution with water and intramuscular injection releases aripiprazole over a period of at least about one week and up to about eight weeks.
摘要翻译：提供了一种制备平均粒径小于100微米但优选大于25微米的无菌阿立哌唑的方法，其采用冲击射流结晶方法。所得粒度的阿立哌唑可用于形成无菌冷冻干燥的阿立哌唑制剂，其在用水和肌内注射后，在至少约一周至多达八周的时间内释放阿立哌唑。

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