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1. 发明授权

US5862999A Method of grinding pharmaceutical substances 失效
标题翻译：药物物质的研磨方法
公开(公告)号：US5862999A
公开(公告)日：1999-01-26
申请号：US491539
申请日：1995-06-15
申请人： David A. Czekai , Larry P. Seaman
发明人： David A. Czekai , Larry P. Seaman
IPC分类号： A61J3/02 , A61K9/14 , B02C17/00 , B02C19/06 , B02C17/16
CPC分类号： B82Y5/00 , A61K9/146 , Y10S977/773 , Y10S977/788 , Y10S977/897 , Y10S977/915 , Y10T24/4051
摘要： A method of preparing submicron particles of a therapeutic or diagnostic agent which comprises grinding the agent in the presence of grinding media having a mean particle size of less than about 75 microns. In a preferred embodiment, the grinding media is a polymeric resin. The method provides extremely fine particles, e.g., less than 100 nanometers in size, free of unacceptable contamination.
摘要翻译：制备治疗或诊断剂的亚微米颗粒的方法，其包括在平均粒度小于约75微米的研磨介质存在下研磨该试剂。在优选的实施方案中，研磨介质是聚合物树脂。该方法提供极细的颗粒，例如小于100纳米的尺寸，没有不可接受的污染。

2. 发明授权

US5571536A Formulations of compounds as nanoparticulate dispersions in digestible oils or fatty acids 失效
标题翻译：在消化油或脂肪酸中作为纳米颗粒分散体的化合物的制剂
公开(公告)号：US5571536A
公开(公告)日：1996-11-05
申请号：US384057
申请日：1995-02-06
申请人： W. Mark Eickhoff , Karl R. Mueller , David A. Engers
发明人： W. Mark Eickhoff , Karl R. Mueller , David A. Engers
IPC分类号： A61K9/10 , A61K9/14 , A61K9/51
CPC分类号： A61K9/5146 , A61K9/10 , A61K9/146 , Y10S514/937 , Y10S514/938 , Y10S514/951 , Y10S977/801 , Y10S977/906 , Y10S977/915
摘要： Nanoparticulate crystalline drug substances formulated in an aqueos phase emulsified in oil, are able to be made at less than 1000 nm size and provide increased bioavailability and lymphatic uptake following oral administration.
摘要翻译：在油中乳化的配位相中配制的纳米颗粒结晶药物能够以小于1000nm的尺寸制成，并且在口服给药后提供增加的生物利用度和淋巴摄取。

3. 发明授权

US5569448A Sulfated nonionic block copolymer surfactants as stabilizer coatings for nanoparticle compositions 失效
标题翻译：硫酸化非离子型嵌段共聚物表面活性剂作为纳米颗粒组合物的稳定剂涂料
公开(公告)号：US5569448A
公开(公告)日：1996-10-29
申请号：US378022
申请日：1995-01-24
申请人： Sui-Ming Wong , Ian M. Newington , Elaine M. Liversidge , Gregory L. McIntire , Alan R. Pitt , Jack M. Shaw
发明人： Sui-Ming Wong , Ian M. Newington , Elaine M. Liversidge , Gregory L. McIntire , Alan R. Pitt , Jack M. Shaw
IPC分类号： A61K9/14 , A61K9/18 , A61K47/48 , A61K49/04
CPC分类号： B82Y5/00 , A61K47/48861 , A61K47/48884 , A61K47/48892 , A61K49/0428 , A61K9/146 , Y10S977/715 , Y10S977/773 , Y10S977/847 , Y10S977/927
摘要： This invention provides a composition comprised of nanoparticles containing a therapeutic or diagnostic agent having a block copolymer linked to at least one anionic group as a surface modifier adsorbed on the surface thereof and a method of making such nanoparticles. The compositions exhibit unexpectedly improved autoclave stability, reduced macrophage uptake, improved toxicological profiles and facilitate particle size reduction such that milling time can be reduced and/or sterile filtration of the nanoparticles can be accomplished.
摘要翻译：本发明提供一种由含有具有与至少一个阴离子基团连接的嵌段共聚物作为吸附在其表面上的表面改性剂的治疗剂或诊断剂的纳米颗粒组成的组合物，以及制备这种纳米颗粒的方法。组合物显示出意想不到的改进的高压釜稳定性，减少的巨噬细胞摄取，改善的毒理学特征和促进粒度降低，从而可以降低研磨时间和/或可以完成纳米颗粒的无菌过滤。

4. 发明授权

US5603916A 3 5-bis alkanoyl amino-2 4 6-triiodobenzyl esters 失效
标题翻译： 3,5-双烷酰基氨基-24,6-三碘苄基酯
公开(公告)号：US5603916A
公开(公告)日：1997-02-18
申请号：US447132
申请日：1995-05-22
申请人： Baldev Singh
发明人： Baldev Singh
IPC分类号： A61K49/04 , C07C233/25 , C07C233/75 , C07C233/88 , C07C69/76 , C07C229/00
CPC分类号： B82Y5/00 , A61K49/0485 , C07C233/25 , C07C233/75 , C07C233/88
摘要： This invention relates to methods of x-ray diagnostic imaging the blood pool, liver, spleen and/or lymph system of a mammal comprising administering a contrast effective amount of a contrast agent having the structure: ##STR1## wherein: n is 2;R.sup.1 is H or alkyl containing from 1 to 4 carbon atoms'R.sup.2 is H, alkyl containing from 1 to 4 carbon atoms, aryl or heteroaryl;and R.sup.3 is alkyl containing from 1 to 18 carbon atoms.This invention further relates to novel contrast agents having the above structure wherein R.sup.1 is H and R.sup.2 and R.sup.3 are CH.sub.3 to x-ray contrast compositions comprising such agents, and to method of x-ray diagnostic imaging utilizing such agents.
摘要翻译：本发明涉及对哺乳动物的血液池，肝脏，脾脏和/或淋巴系统进行x射线诊断成像的方法，该方法包括给予对比有效量的具有以下结构的造影剂：其中n为2; R 1为H或含有1至4个碳原子的烷基，R 2为H，含有1至4个碳原子的烷基，芳基或杂芳基; 并且R 3是含有1至18个碳原子的烷基。本发明还涉及具有上述结构的新型造影剂，其中R1是H，R2和R3是包含这些试剂的CH3至X射线造影剂组合物，以及使用这种试剂的X射线诊断成像方法。

5. 发明授权

US5628981A Formulations of oral gastrointestinal diagnostic x-ray contrast agents and oral gastrointestinal therapeutic agents 失效
标题翻译：口服胃肠道诊断X线造影剂和口服胃肠道治疗剂的配方
公开(公告)号：US5628981A
公开(公告)日：1997-05-13
申请号：US366841
申请日：1994-12-30
申请人： Gary Liversidge , W. Mark Eickhoff , Kathleen J. Illig , Pramod Sarpotdar , Stephen B. Ruddy
发明人： Gary Liversidge , W. Mark Eickhoff , Kathleen J. Illig , Pramod Sarpotdar , Stephen B. Ruddy
IPC分类号： A61K9/14 , A61K9/51 , A61K49/04 , A61M36/14
CPC分类号： A61K49/049 , A61K49/0423 , A61K9/146 , A61K9/5146 , B82Y5/00 , Y10S514/975 , Y10S977/906
摘要： Nanoparticulate crystalline x-ray contrast agents are formulated with stabilizers to enhance contact between the crystalline x-ray contrast agents and the gastrointestinal tract.Nanoparticulate crystalline therapeutic substances also formulated with stabilizers to enhance contact between the crystalline therapeutic substances and the gastrointestinal tract and to provide extended therapeutic effect.
摘要翻译：用稳定剂配制纳米颗粒结晶x射线造影剂以增强结晶x射线造影剂与胃肠道之间的接触。纳米颗粒结晶治疗物质也与稳定剂配制以增强结晶治疗物质与胃肠道之间的接触并提供延长的治疗效果。

6. 发明授权

US5560932A Microprecipitation of nanoparticulate pharmaceutical agents 失效
标题翻译：纳米颗粒药剂的微沉淀
公开(公告)号：US5560932A
公开(公告)日：1996-10-01
申请号：US370955
申请日：1995-01-10
申请人： Pranab Bagchi , Piotr H. Karpinski , Gregory L. McIntire
发明人： Pranab Bagchi , Piotr H. Karpinski , Gregory L. McIntire
IPC分类号： A61K9/14 , A61K49/04
CPC分类号： B82Y5/00 , A61K49/049 , A61K9/145 , A61K9/146 , Y10S977/881 , Y10S977/927
摘要： This invention describes the preparation of nanoparticulate pharmaceutical agent dispersion via a process that comprises the dissolution of the said pharmaceutical agent in an alkaline solution and then neutralizing the said solution with an acid in the presence of a suitable surface-modifying, surface-active agent to form a fine particle dispersion of the said pharmaceutical agent. This can be preferably followed by steps of diafiltration clean-up of the dispersion and then concentration of it to a desired level. This process of dispersion preparation leads to microcrystalline particles of Z-average diameters smaller than 400 nm as measured by photon correlation spectroscopy. Various modification of precipitation schemes are described, many of which are suitable for large-scale manufacture of these agent dispersions.
摘要翻译：本发明描述了通过包括将所述药剂溶解在碱性溶液中然后在合适的表面改性表面活性剂存在下用酸中和所述溶液的方法制备纳米颗粒药剂分散体，形成所述药剂的细颗粒分散体。这可以优选地随后是分散体的渗滤清洗步骤，然后将其浓缩到期望的水平。这种分散制备过程导致通过光子相关光谱测量的Z平均直径小于400nm的微晶颗粒。描述了各种改性的沉淀方案，其中许多适用于这些试剂分散体的大规模制造。

7. 发明授权

US5518187A Method of grinding pharmaceutical substances 失效
标题翻译：药物物质的研磨方法
公开(公告)号：US5518187A
公开(公告)日：1996-05-21
申请号：US180827
申请日：1994-01-12
申请人： Joseph A. Bruno , Brian D. Doty , Evan Gustow , Kathleen J. Illig , Nats Rajagopalan , Pramod Sarpotdar
发明人： Joseph A. Bruno , Brian D. Doty , Evan Gustow , Kathleen J. Illig , Nats Rajagopalan , Pramod Sarpotdar
IPC分类号： A61J3/02 , A61K9/14 , A61K9/16 , A61K9/26 , A61K31/19 , A61K31/192 , A61K49/00 , A61K49/04 , A61K51/00 , B02C17/00 , B02C17/20 , B02C19/00 , G03C1/005 , B02C23/18
CPC分类号： A61K9/146 , A61K9/14 , A61K9/1688 , G03C1/005 , Y10S977/775 , Y10S977/788 , Y10S977/90 , Y10S977/928
摘要： A method of preparing particles of a drug substance or diagnostic imaging agent which comprises grinding the drug substance or imaging agent in the presence of grinding media comprising a polymeric resin. The method provides particles exhibiting reduced contamination.
摘要翻译：一种制备药物或诊断显像剂的颗粒的方法，其包括在包含聚合物树脂的研磨介质的存在下研磨药物或显像剂。该方法提供表现出减少污染的颗粒。

8. 发明授权

US5622938A Sugar base surfactant for nanocrystals 失效
标题翻译：用于纳米晶体的糖基表面活性剂
公开(公告)号：US5622938A
公开(公告)日：1997-04-22
申请号：US444796
申请日：1995-05-19
申请人： Sui-Ming Wong
发明人： Sui-Ming Wong
IPC分类号： A61K9/107 , A61K9/14 , A61K9/18 , A61K47/06 , A61K49/04 , B82B1/00 , A01N43/04 , A61K31/70
CPC分类号： B82Y5/00 , A61K49/049 , A61K9/145
摘要： Dispersible particles consisting essentially of a crystalline drug substance having a surface modifier having the formula: ##STR1## wherein R is phenyl-(CH.sub.2).sub.10 CO or C.sub.12 H.sub.25 NHCO adsorbed on the surface thereof in an amount sufficient to maintain an effective average particle size of less than about 400 nm, methods for the preparation of such particles and dispersions containing the particles. Pharmaceutical compositions containing the particles exhibit unexpected bioavailability and are useful in methods of treating mammals.
摘要翻译：基本上由具有下式的表面改性剂的结晶药物组成的分散性颗粒：其中R是以足以维持有效平均值的量吸附在其表面上的苯基 - （CH2）10CO或C12H25NHCO 粒径小于约400nm，制备这种颗粒的方法和含有颗粒的分散体。含有该颗粒的药物组合物表现出意想不到的生物利用度，并且可用于治疗哺乳动物的方法。

9. 发明授权

US5580579A Site-specific adhesion within the GI tract using nanoparticles stabilized by high molecular weight, linear poly (ethylene oxide) polymers 失效
标题翻译：使用由高分子量线性聚（环氧乙烷）聚合物稳定的纳米粒子在胃肠道内的位点特异性粘附
公开(公告)号：US5580579A
公开(公告)日：1996-12-03
申请号：US388878
申请日：1995-02-15
申请人： Stephen B. Ruddy , W. Mark Eickhoff , Gary Liversidge
发明人： Stephen B. Ruddy , W. Mark Eickhoff , Gary Liversidge
IPC分类号： A61K9/14 , A61K49/04 , A61K9/107 , A61K123/00
CPC分类号： A61K49/0404 , A61K49/0428 , A61K9/146 , B82Y5/00 , Y10S514/937 , Y10S514/938 , Y10S514/939 , Y10S514/943 , Y10S977/795 , Y10S977/915 , Y10S977/927
摘要： Nanoparticulate crystalline therapeutic or diagnostic substances formulated with stabilizers and high molecular weight, linear poly(ethylene oxide) polymers, enhance contact between the crystalline therapeutic or diagnostic substances and the gastrointestinal tract providing site-specific and extended therapeutic or diagnostic effect.
摘要翻译：用稳定剂和高分子量线性聚（环氧乙烷）聚合物配制的纳米晶状治疗或诊断物质增强结晶治疗或诊断物质与胃肠道之间的接触，从而提供特异性和延长的治疗或诊断效果。

10. 发明授权

US5573783A Redispersible nanoparticulate film matrices with protective overcoats 失效
标题翻译：具有保护性外涂层的可再分散纳米颗粒膜基质
公开(公告)号：US5573783A
公开(公告)日：1996-11-12
申请号：US387651
申请日：1995-02-13
申请人： Mark A. Desieno , Gregg Stetsko
发明人： Mark A. Desieno , Gregg Stetsko
IPC分类号： A61K9/50 , A61K9/14 , A61K9/16 , A61K47/30 , B82B1/00
CPC分类号： A61K9/1676 , A61K9/146
摘要： A pharmaceutical film matrix comprising nanoparticles of a low solubility drug associated with a steric stabilizer and a film dispersing agent is coated on the surface of carrier particles and overcoated with a protective layer. Pharmaceutical compositions comprising the film matrix-coated carrier exhibit excellent bioavailability, are useful in methods of treating mammals and are extremely stable in that they are capable of being redispersed without extensive agglomeration into larger particles after being stored.
摘要翻译：包含与空间稳定剂和薄膜分散剂相关的低溶解度药物的纳米颗粒的药物膜基质涂覆在载体颗粒的表面上并用保护层涂覆。包含膜基质涂覆的载体的药物组合物表现出优异的生物利用度，可用于治疗哺乳动物的方法，并且非常稳定，因为它们能够在储存后没有大量聚集而没有广泛的聚集成较大的颗粒。

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