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1. 发明授权

US06974593B2 Insoluble drug delivery 失效
标题翻译：不溶性药物递送
公开(公告)号：US06974593B2
公开(公告)日：2005-12-13
申请号：US10458071
申请日：2003-06-09
申请人： Inge B Henriksen , Awadesh K. Mishra , Gary W. Pace , Keith P. Johnston , Simon Mawson
发明人： Inge B Henriksen , Awadesh K. Mishra , Gary W. Pace , Keith P. Johnston , Simon Mawson
IPC分类号： A61J3/06 , A61K9/14 , A61K9/16 , A61K31/235 , A61K31/405 , A61K38/13 , B01F1/00 , B01F3/12 , B01F5/02 , B01J2/06 , B01J3/00
CPC分类号： B01J3/008 , A61K9/14 , A61K9/145 , A61K9/146 , A61K9/1688 , B01F1/00 , B01F3/1214 , B01F3/1271 , B01F5/02 , B01F5/0287 , B01F2003/0064 , B01F2003/125 , B01F2215/0032 , Y02P20/544 , Y10S977/896 , Y10S977/906
摘要： Particles of water insoluble biologically active compounds, particularly water-insoluble drugs, with an average size of 100 nm to about 300 nm, are prepared by dissolving the compound in a solution then spraying the solution into compressed gaz, liquid or supercritical fluid in the presence of appropriate surface modifiers.
摘要翻译：通过将化合物溶解在溶液中，然后在存在下将溶液喷射到压缩的gaz，液体或超临界流体中来制备水不溶性生物活性化合物，特别是水不溶性药物，平均粒径为100nm至约300nm的颗粒的适当的表面改性剂。

2. 发明授权

US06576264B1 Insoluble drug delivery 有权
标题翻译：不溶性药物递送
公开(公告)号：US06576264B1
公开(公告)日：2003-06-10
申请号：US09202504
申请日：1999-03-12
申请人： Inge B Henriksen , Awadesh K. Mishra , Gary W. Pace , Keith P. Johnston , Simon Mawson
发明人： Inge B Henriksen , Awadesh K. Mishra , Gary W. Pace , Keith P. Johnston , Simon Mawson
IPC分类号： A61K916
CPC分类号： B01J3/008 , A61K9/14 , A61K9/145 , A61K9/146 , A61K9/1688 , B01F1/00 , B01F3/1214 , B01F3/1271 , B01F5/02 , B01F5/0287 , B01F2003/0064 , B01F2003/125 , B01F2215/0032 , Y02P20/544 , Y10S977/896 , Y10S977/906
摘要： Particles of water insoluble biologically active compounds, particularly water-insoluble drugs, with an average size of 100 nm to about 300 nm, are prepared by dissolving the compound in a solution then spraying the solution into compressed gaz, liquid or supercritical fluid in the presence of appropriate surface modifiers.
摘要翻译：通过将化合物溶解在溶液中，然后在存在下将溶液喷射到压缩的gaz，液体或超临界流体中来制备水不溶性生物活性化合物，特别是水不溶性药物，平均粒径为100nm至约300nm的颗粒的适当的表面改性剂。

3. 发明授权

US06726919B2 Injectable dispersion of propofol 失效
标题翻译：异丙酚注射分散体
公开(公告)号：US06726919B2
公开(公告)日：2004-04-27
申请号：US09880104
申请日：2001-06-14
申请人： Gary W. Pace , Michael G. Vachon , Awadesh K. Mishra , Robert A. Snow
发明人： Gary W. Pace , Michael G. Vachon , Awadesh K. Mishra , Robert A. Snow
IPC分类号： A61F1300
CPC分类号： A61K31/7016 , A61K9/0019 , A61K9/1075 , A61K31/05 , A61K31/14 , A61K47/10 , A61K47/12 , A61K47/14 , A61K47/24 , A61K47/26 , A61K47/44 , Y02A50/473
摘要： A sterile, injectable homogenized dispersion of micromatrices or microdroplets having a mean diameter from about 50 nm to about 1000 nm comprising about 1% to about 7.5% of propofol, about 1% to about 8% of a propofol-soluble diluent, and about 0.67% to about 5% of a surface stabilizing amphiphilic agent suspended in an aqueous medium containing a synergetic quantity of antimicrobial agent and a tonicity modifying amount of a pharmaceutically acceptable water-soluble hydroxyl-group-containing excipient, wherein the ratio of propofol to diluent is in the range of about 0.25 to about 7.5 while the ratio of propofol to amphiphilic agent is in the range from about 0.4 to about 1.5, and wherein the viscosity of the dispersion is in the range of 1.1 to 8 cps, processes for the formation of the dispersion, and methods of use are disclosed.
摘要翻译：平均直径约50nm至约1000nm的微量或微滴的无菌注射匀浆分散体，其包含约1％至约7.5％的异丙酚，约1％至约8％的异丙酚可溶性稀释剂和约0.67 悬浮在含有协同量的抗微生物剂的水性介质中的表面稳定两亲剂的百分比至约5％，以及药学上可接受的水溶性含羟基赋形剂的张力调节量，其中异丙酚与稀释剂的比例为在约0.25至约7.5的范围内，而丙泊酚与两亲剂的比例在约0.4至约1.5的范围内，并且其中分散体的粘度在1.1至8cps的范围内，形成公开了分散体和使用方法。

4. 发明授权

US06696084B2 Spray drying process and compositions of fenofibrate 有权
标题翻译：喷雾干燥工艺和非诺贝特组合物
公开(公告)号：US06696084B2
公开(公告)日：2004-02-24
申请号：US09838593
申请日：2001-04-20
申请人： Gary W. Pace , Awadesh K. Mishra , Robert A. Snow , Indu Parikh , Pol-Henri W. Guivarc'h
发明人： Gary W. Pace , Awadesh K. Mishra , Robert A. Snow , Indu Parikh , Pol-Henri W. Guivarc'h
IPC分类号： A61K914
CPC分类号： A61K31/66 , A61K9/145 , A61K9/1623 , A61K31/216 , A61K31/22 , A61K31/365 , A61K31/40 , A61K31/405 , A61K31/44 , A61K31/505 , A61K45/06 , A61K31/215 , A61K2300/00
摘要： The present invention relates to a novel spray drying process for the preparation of pharmaceutical compositions containing small particles of phospholipid-stabilized fenofibrate. This invention also relates to spray dried powdered compositions prepared according to this process, and to dosage forms of fenofibrate (capsules, tablets, powders, granules, and dispersions) prepared from these powdered compositions. The powdered compositions and dosage forms are useful in the treatment of dyslipidemia and dyslipoproteinemia and have the advantage that they provide reduced in vivo variability in the bioavailability of fenofibrate active species among fed and fasted patients when administered orally.
摘要翻译：本发明涉及一种用于制备含有磷脂稳定的非诺贝特的小颗粒的药物组合物的新型喷雾干燥方法。本发明还涉及根据该方法制备的喷雾干燥的粉末组合物，以及由这些粉末状组合物制备的非诺贝特（胶囊，片剂，粉末，颗粒剂和分散体）的剂型。粉末组合物和剂型可用于治疗血脂异常和血脂异常，并且具有这样的优点：当口服给药时，它们在进食和禁食患者中提供非诺贝特活性物质的生物利用度的体内变异性降低。

5. 发明授权

US06682761B2 Water-insoluble drug particle process 有权
标题翻译：水不溶性药物颗粒过程
公开(公告)号：US06682761B2
公开(公告)日：2004-01-27
申请号：US09838540
申请日：2001-04-20
申请人： Gary W. Pace , Awadesh K. Mishra
发明人： Gary W. Pace , Awadesh K. Mishra
IPC分类号： A61K914
CPC分类号： A61K9/1688 , A61K9/145
摘要： This invention relates to process for the preparation of small particles containing a poorly water soluble drug comprising (a) mixing at high shear an admixture of a poorly water soluble drug and one or more than one surface active substance in an aqueous carrier in the absence of an organic solvent within a first temperature range at or above the melting point of the poorly water soluble drug to form a heated suspension containing the drug, then (b) homogenizing said heated suspension in a first pressure range and within said first temperature range to form a heated homogenate containing the drug, then (c) cooling said heated homogenate to a second temperature range below the melting temperature of the poorly water soluble drug to form a transiently stable cooled homogenate containing the drug, then (d) applying a particle stabilizing energetic process to said cooled homogenate within a second temperature range below the melting point of the drug and in a second pressure range to form a cooled dispersion of stabilized small particles containing the drug, and then (e) optionally drying the cooled dispersion to form dried small particles containing the poorly water soluble drug.
摘要翻译：本发明涉及制备含水难溶性药物的小颗粒的方法，其包括（a）在高剪切下混合水不溶性药物与一种或多于一种表面活性物质在水性载体中的混合物，在低水溶性药物的熔点以上的第一温度范围内的有机溶剂，形成含有药物的加热悬浮液，然后（b）在所述第一压力范围内并在所述第一温度范围内使所述加热的悬浮液均化，形成含有药物的加热匀浆，然后（c）将所述加热的匀浆冷却至低于难溶性水溶性药物的熔融温度的第二温度范围，以形成含有药物的瞬时稳定的冷却匀浆，然后（d）在低于药物熔点的第二温度范围内和在形成的第二压力范围内对所述冷却的匀浆进行处理含有药物的稳定的小颗粒的冷却分散体，然后（e）任选地干燥冷却的分散体以形成干燥的含水难溶性药物的小颗粒。

6. 发明申请

US20120316189A1 METHODS AND COMPOSITIONS FOR REDUCING THE RISK ASSOCIATED WITH THE ADMINISTRATION OF OPIOID ANALGESICS IN PATIENTS DIAGNOSED OR UNDIAGNOSED RESPIRATORY ILLNESS 审中-公开
标题翻译：方法和组合物，用于降低与诊断或不良反应无效的患者中的阿片类药物治疗相关的风险
公开(公告)号：US20120316189A1
公开(公告)日：2012-12-13
申请号：US13444073
申请日：2012-04-11
申请人： Gary W. Pace , Maree T. Smith
发明人： Gary W. Pace , Maree T. Smith
IPC分类号： A61K31/485 , A61P25/04
CPC分类号： A61K45/06 , A61K31/445 , A61K31/485 , A61K2300/00
摘要： The present invention relates to methods for reducing the risk associated with the administration of opioid analgesics in patient diagnosed or undiagnosed with respiratory illness by administering an analgesic composition comprising a sub-analgesic dosage of a p-opioid agonist selected from the group consisting a morphine, fentanyl, sufentanil, alfentanil, oxymorphone and hydromorphone, or a pharmaceutically acceptable salt thereof, and a sub-analgesic dosage of oxycodone which is a κ2-opioid agonist or a pharmaceutically acceptable salt thereof.
摘要翻译：本发明涉及通过施用镇痛组合物来降低与诊断或未诊断为呼吸系统疾病的患者中阿片样镇痛药相关的风险的方法，所述止痛组合物包含选自以下组中的β-阿片样物质激动剂的亚类镇痛剂：吗啡，芬太尼，舒芬太尼，阿芬太尼，羟吗啡酮和氢吗啡酮，或其药学上可接受的盐，以及作为阿片样物质激动剂或其药学上可接受的盐的羟考酮的次镇痛剂量。

7. 发明申请

US20110195989A1 Controlled Release Formulations of Opioids 审中-公开
标题翻译：阿片类药物的控制释放制剂
公开(公告)号：US20110195989A1
公开(公告)日：2011-08-11
申请号：US13024319
申请日：2011-02-09
申请人： Edward M. Rudnic , Michael Vachon , Gary W. Pace , Joseph Berry , Felix de la Iglesia
发明人： Edward M. Rudnic , Michael Vachon , Gary W. Pace , Joseph Berry , Felix de la Iglesia
IPC分类号： A61K31/485 , A61P25/04
CPC分类号： A61K45/06 , A61K9/2081 , A61K9/209 , A61K9/5026 , A61K9/5042 , A61K9/5073 , A61K31/485 , A61K2300/00
摘要： Pharmaceutical formulations containing opioid components that each has a release profile. The components may provide immediate or controlled release of the opioid. The invention is also directed to methods of controlling release of one or more opioid compounds and methods of treating pain.
摘要翻译：含有阿片样物质成分的药物制剂，各自具有释放特征。组分可以提供阿片样物质的即时或受控释放。本发明还涉及控制一种或多种阿片类化合物释放的方法和治疗疼痛的方法。

8. 发明申请

US20090291975A1 DUAL OPIOID PAIN THERAPY 审中-公开
标题翻译：双重疼痛治疗
公开(公告)号：US20090291975A1
公开(公告)日：2009-11-26
申请号：US12469438
申请日：2009-05-20
申请人： WARREN STERN , Gary W. Pace , Felix A. de la IgLesia , Maree Smith , Patricia Richards
发明人： WARREN STERN , Gary W. Pace , Felix A. de la IgLesia , Maree Smith , Patricia Richards
IPC分类号： A61K31/485 , A61P29/00
CPC分类号： A61K31/485 , A61K9/0095 , A61K2300/00
摘要： Provided are pharmaceutical compositions and methods for the alleviation of pain in a patient with optimal ratios of morphine and oxycodone that provide superior analgesic efficacy and lower incidence of adverse side effects compared to morphine and oxycodone alone. The pharmaceutical compositions comprise morphine and oxycodone, or pharmaceutically acceptable salts thereof, in ratios of about 3 to 2 to about 1 to 2, morphine to oxycodone by weight.
摘要翻译：提供了与吗啡和羟考酮相比，吗啡和羟考酮的最佳比例减轻疼痛的药物组合物和方法，其提供优异的止痛效力和较低的与吗啡和羟考酮相比的不利副作用的发生率。药物组合物包含约3至2至约1至2的吗啡和羟考酮或其药学上可接受的盐，吗啡与羟考酮的重量比。

9. 发明授权

US07041705B2 Injectable aqueous dispersions of propofol 失效
公开(公告)号：US07041705B2
公开(公告)日：2006-05-09
申请号：US09820371
申请日：2001-03-26
申请人： Awadhesh K. Mishra , Gary W. Pace , Michael G Vachon
发明人： Awadhesh K. Mishra , Gary W. Pace , Michael G Vachon
IPC分类号： A01N31/08 , A61K31/05
CPC分类号： A61K9/1075 , A61K9/0019 , A61K31/05 , A61K47/14 , A61K47/24 , A61K47/28 , Y02A50/473 , Y10S514/816 , Y10S514/817 , Y10S514/818 , Y10S514/938
摘要： Irritation upon injection of a formulation containing propofol is reduced or substantially eliminated by administering a stable, sterile, and antimicrobial aqueous dispersion comprising a water-insoluble microdroplet matrix of mean diameter from about 50 nm to about 1000 nm consisting essentially of about 1% to about 15% of propofol, up to about 7% of a propofol-soluble diluent, and about 0.8% to about 4% of a surface stabilizing amphiphilic aent. The aqueous phase includes a pharmaceutically acceptable water-soluble polyhydroxy tonicity modifier. The propofol-containing dispersion is devoid of additional bactericidal or bacteriostatic preservative agents.

10. 发明授权

US06604698B2 Media milling 有权
公开(公告)号：US06604698B2
公开(公告)日：2003-08-12
申请号：US09852054
申请日：2001-05-10
申请人： Frank H. Verhoff , Robert A. Snow , Gary W. Pace
发明人： Frank H. Verhoff , Robert A. Snow , Gary W. Pace
IPC分类号： B02C1716
CPC分类号： A61K9/14 , A61K9/145 , B02C17/161 , Y10S977/775 , Y10S977/797 , Y10S977/90
摘要： This invention describes a process for preparing a dispersion of solid particles of a milled substrate in a fluid carrier comprising the steps of (a) providing a plurality of large size milling media to the milling chamber of a media mill and forming a depth filter therefrom on an exit screen or separator in the milling chamber; (b) adding to said milling chamber a plurality of small size milling media optionally containing additional large size milling media, a conglomerate of a solid substance comprising a substrate to be milled and optionally one or more than one surface active substance, and a fluid carrier; (c) milling said conglomerate in said milling chamber to produce very small milled substrate product particles; and (d) separating said milled substrate particles suspended in said fluid carrier from the media through said depth filter; wherein the exit screen comprises openings of size S0; the large size media have a size distribution S1 of which all are larger than S0; the small size media have a size distribution S2 which are smaller than S0; the very small milled substrate particles have a size distribution S3 and are smaller than all of the small media; and the large size media and the small size media are essentially retained in the milling chamber.

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