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1. 发明授权

US4851228A Multiparticulate controlled porosity osmotic 失效
标题翻译：多重控制孔隙渗透
公开(公告)号：US4851228A
公开(公告)日：1989-07-25
申请号：US73596
申请日：1987-07-15
申请人： Gaylen M. Zentner , Kenneth J. Himmelstein , Gerald S. Rork
发明人： Gaylen M. Zentner , Kenneth J. Himmelstein , Gerald S. Rork
IPC分类号： A61K9/00 , A61K9/64
CPC分类号： A61K9/0004
摘要： The instant invention is directed to a multiparticulate osmotic pump, for the controlled release of a pharmaceutically active agent to an environment of use, said pump comprising:(I) a carrier medium which does not maintain its integrity in the environment of use;(II) a multiple of tiny osmotic pump elements each consisting essentially of:(A) a core comprises at least one pharmacologically active agent soluble in an external fluid, or a mixture of an agent having a limited solubility in the external fluid with an osmotically effective solute that is soluble in the fluid, which exhibit an osmotic pressure gradient across the wall against the external fluid surrounded by(B) a rate controlling water insoluble wall, having a fluid permeability of 6.96.times.10.sup.-18 to 6.96.times.10.sup.14 cm.sup.3 sec/g and a reflection coefficient of less than 0.5, prepared from:(i) a polymer permeable to water but impermeable to solute and(ii) 0.1 to 60% by weight, based on the total weight of (i) and (ii), of at least one pH insensitive pore forming additive dispersed throughout said wall.
摘要翻译：本发明涉及多颗粒渗透泵，用于将药物活性剂控制释放到使用环境中，所述泵包括：（I）在使用环境中不保持其完整性的载体介质; （II）多个微小的渗透泵元件，其各自主要由以下组成：（A）芯包含至少一种可溶于外部流体的药理学活性剂，或在外部流体中具有有限溶解度的试剂与渗透性的混合物可溶于流体的有效溶质，其表现出渗透压梯度横跨壁对抗由外界流体包围的外部流体（B）速率控制水不溶性壁，流体渗透率为6.96×10-18至6.96×1013cm3 / g 和反射系数小于0.5，由以下因素制备：（i）可渗透水但不溶于溶质的聚合物，和（ii）基于（i）和（ii）的总重量为0.1-60重量％至少一种pH不敏感的成孔添加剂分散在整个壁上。

2. 发明授权

US4968507A Controlled porosity osmotic pump 失效
标题翻译：可控孔隙渗透泵
公开(公告)号：US4968507A
公开(公告)日：1990-11-06
申请号：US073781
申请日：1987-07-15
申请人： Gaylen M. Zentner , Gerald S. Rork , Kenneth J. Himmelstein
发明人： Gaylen M. Zentner , Gerald S. Rork , Kenneth J. Himmelstein
IPC分类号： A61K9/00 , A61K9/64
CPC分类号： A61K9/0004
摘要： The instant invention is directed to an osmotic pump comprising:(A) at least one active agent surrounded by(B) a rate controlling water insoluble wall, having a fluid permeability of 6.96.times.10.sup.-18 to 6.96.times.10.sup.-14 cm.sup.3 sec/g and a reflection coefficient of less than 1, prepared from:(i) a polymer permeable to water but impermeable to solute and(ii) 0.1 to 60% by weight, based on the total weight of (i) and (ii), of at least one pH insensitive pore forming additive dispersed throughout said wall.
摘要翻译：本发明涉及一种渗透泵，其包括：（A）由（B）速率控制水不溶性壁包围的至少一种活性剂，其流体渗透性为6.96×10-18至6.96×10-14厘米3秒/克，反应系数小于1，由以下因素制备：（i）可渗透水但不溶于溶质的聚合物，和（ii）基于（i）和（ii）的总重量为0.1-60重量％至少一种pH不敏感的成孔添加剂分散在整个所述壁上。

3. 发明授权

US4780319A Organic acids as catalysts for the erosion of polymers 失效
标题翻译：有机酸作为聚合物侵蚀的催化剂
公开(公告)号：US4780319A
公开(公告)日：1988-10-25
申请号：US33565
申请日：1987-04-03
申请人： Gaylen M. Zentner , Kenneth J. Himmelstein , Stefano A. Pogany , Cheryl Ringeisen
发明人： Gaylen M. Zentner , Kenneth J. Himmelstein , Stefano A. Pogany , Cheryl Ringeisen
IPC分类号： A61K9/20 , A61K31/19 , A61K31/20
CPC分类号： A61K9/204
摘要： The invention relates to the use of carboxylic acids incorporated as a catalyst in poly(orthoester)s and other acid labile polymers such that upon exposure to aqueous environments the acid catalyzes the erosion of the polymer matrix. The rate of release of a drug substance incorporated into or surrounded by the poly(orthoester) or other acid labile polymer can be controlled in that the drug is released as the polymer is eroded in response to the catalytic action of the acid incorporated therein.
摘要翻译：本发明涉及在聚（原酸酯）和其它酸不稳定聚合物中引入作为催化剂的羧酸的用途，使得当暴露于水性环境时，酸催化聚合物基质的侵蚀。可以控制掺入聚（原酸酯）或其他酸不稳定聚合物中或被聚（原酸酯）或其它酸不稳定聚合物包围的药物的释放速率，因为随着聚合物在其中掺入的酸的催化作用而被侵蚀，药物被释放。

4. 发明授权

US5276044A Leukotriene receptor antagonist and antihistamine complex pharmaceutical compositions 失效
标题翻译：白三烯受体拮抗剂和抗组胺药物组合物
公开(公告)号：US5276044A
公开(公告)日：1994-01-04
申请号：US745232
申请日：1991-08-14
申请人： Gyorgy F. Ambrus , Kenneth J. Himmelstein , David F. Woodward
发明人： Gyorgy F. Ambrus , Kenneth J. Himmelstein , David F. Woodward
IPC分类号： A61K31/19 , A61K31/40 , A61K31/44 , A61K31/445 , A61K31/495 , A61K31/54 , A61K45/00 , A61K45/06 , A61K47/10 , A61K47/14 , A61K47/22 , A61P43/00
CPC分类号： A61K45/06 , A61K31/19 , A61K31/40 , A61K31/44 , A61K31/445 , A61K31/495 , A61K31/54
摘要： Pharmaceutical compositions are disclosed which effectively treat the symptoms of hypersensitivity diseases without irritation. The pharmaceutical compositions are complexes of at least one leukotriene receptor antagonist and at least one antihistamine. The complexes can be formulated in low viscosity solutions for administering to an individual as an aerosol or drops or through intravenous, subcutaneous, or intramuscular injection. Alternatively, the complexes can be formulated in high viscosity creams for topical delivery to the skin or ocular environment.
摘要翻译：公开了有效治疗超敏反应疾病症状而不刺激的药物组合物。药物组合物是至少一种白细胞三烯受体拮抗剂和至少一种抗组胺药物的复合物。复合物可以配制在低粘度溶液中，以个体作为气雾剂或滴剂或通过静脉内，皮下或肌内注射给药。或者，可以将配合物配制成高粘度乳膏，用于局部递送至皮肤或眼睛环境。

5. 发明授权

US5252318A Reversible gelation compositions and methods of use 失效
标题翻译：可逆凝胶组合物和使用方法
公开(公告)号：US5252318A
公开(公告)日：1993-10-12
申请号：US539061
申请日：1990-06-15
申请人： Abhay Joshi , Shulin Ding , Kenneth J. Himmelstein
发明人： Abhay Joshi , Shulin Ding , Kenneth J. Himmelstein
IPC分类号： A61K9/00 , A61K9/06 , A61K9/107 , A61K9/16 , A61K47/10 , A61K47/18 , A61K47/32 , A61K47/38 , A61K31/19 , A01N25/04 , A61K31/745
CPC分类号： A61K9/0048 , A61K47/10 , A61K47/18 , A61K47/32 , A61K47/38 , A61K9/0019 , A61K9/06 , A61K9/1647 , Y10S514/912 , Y10S514/913 , Y10S514/914 , Y10S514/915 , Y10S514/938 , Y10S514/942
摘要： Reversibly gelling aqueous compositions are disclosed which undergo significant changes in viscosity in response to substantially simultaneous changes in both temperature and pH. The compositions are formed of relatively low concentrations of a stable combination of at least one pH-sensitive reversibly gelling polymer and at least one temperature-sensitive reversibly gelling polymer. The compositions can be formulated to exhibit a sol-gel transition over a wide range of conditions and viscosities and may be modified to incorporate a pharmaceutical compound for utilization as droppable or injectable drug delivery systems which will gel following administration to a physiological system for the sustained delivery of such pharmaceutical compounds.
摘要翻译：公开了可反射胶凝的含水组合物，其响应于温度和pH两者的基本上同时的变化而经历显着的粘度变化。组合物由相对低浓度的至少一种pH敏感性可逆胶凝聚合物和至少一种温度敏感的可逆胶凝聚合物的稳定组合形成。组合物可以配制成在宽范围的条件和粘度下显示出溶胶 - 凝胶转变，并且可以被修饰以引入药物化合物以用作可滴注或可注射的药物递送系统，其将在施用于生理系统之后凝胶用于持续的这种药物化合物的递送。

6. 发明授权

US4475916A Osmotic drug delivery system 失效
标题翻译：渗透药物输送系统
公开(公告)号：US4475916A
公开(公告)日：1984-10-09
申请号：US359324
申请日：1982-03-18
申请人： Kenneth J. Himmelstein
发明人： Kenneth J. Himmelstein
IPC分类号： A61K9/00 , A61K9/22 , A61M31/00
CPC分类号： A61K9/0004
摘要： An osmotic drug (or other beneficial substance) delivery system comprises a compartment with one or more chambers in series formed by an external shell and chamber-dividing walls of a microporous material and successive overlayers of semipermeable membranes completely covering the outer shell of all but one chamber and substantially covering the outer shell of that one chamber, each successive overlayer completely covering all but one more chamber and substantially covering that one more chamber. Osmotic agents, adjuvants, enzymes, drugs, pro-drugs, pesticides and the like are incorporated in the chambers covered by the semipermeable membranes, and external fluids that diffuse into that chamber form solutions and by osmotic pressure are forced through the microporous chamber-dividing wall to the drug or drug-forming chamber to form a solution thereof and then through the exposed microporous shell to the exterior of the device at a rate controlled by the permeability of the semipermeable overlay and the osmotic pressure gradient across the shell.
摘要翻译：渗透药物（或其他有益物质）递送系统包括具有一个或多个串联形成的室的室，其由外部壳体和微孔材料的室分隔壁以及完全覆盖所有除了一个的所有外壳的半透膜的连续覆盖层并且基本上覆盖该一个室的外壳，每个连续的覆盖层完全覆盖除了一个更多的室之外的所有室，并且基本上覆盖该另一个室。将渗透剂，佐剂，酶，药物，前药，农药等掺入由半透膜覆盖的室中，并且扩散到该室中的外部流体形成溶液并通过渗透压被迫通过微孔室分离壁，以形成其溶液，然后通过暴露的微孔外壳以通过半透膜覆盖层的渗透性和穿过壳体的渗透压梯度控制的速率通过外露的设备。

7. 发明授权

US5296228A Compositions for controlled delivery of pharmaceutical compounds 失效
标题翻译：用于药物化合物的控制递送的组合物
公开(公告)号：US5296228A
公开(公告)日：1994-03-22
申请号：US850866
申请日：1992-03-13
申请人： Nienyuan J. Chang , Kenneth J. Himmelstein
发明人： Nienyuan J. Chang , Kenneth J. Himmelstein
IPC分类号： A61K9/107 , A61K9/00 , A61K47/32 , A61K47/38 , A61K47/48 , A61K9/10 , A61K47/34 , A61K47/36
CPC分类号： A61K47/38 , A61K47/32 , A61K47/48184 , A61K9/0048 , Y10S514/944 , Y10S514/951
摘要： Sustained release pharmaceutical compound delivery compositions and methods for their production are disclosed wherein ion exchange resin particles are loaded with releasably bound pharmaceutical compounds and incorporated in an aqueous reversibly gelling polymeric solution. The pores of the ion exchange resin are sufficiently small to lock in the pharmaceutical compound without exposure to the large polymer molecules. The pharmaceutical compound remains bound within the pores of the ion exchange resin particles until after administration to a target tissue site where small ions migrate into the pores and initiate an exchange reaction.
摘要翻译：公开了缓释药物组合物递送组合物及其生产方法，其中离子交换树脂颗粒装载有可释放结合的药物化合物并且并入水性可逆胶凝聚合物溶液中。离子交换树脂的孔隙足够小以在不暴露于大的聚合物分子的情况下锁定药物化合物。药物化合物保持结合在离子交换树脂颗粒的孔内，直到给予目标组织部位，其中小离子迁移到孔中并开始交换反应。

8. 发明授权

US3965036A Regeneration of activated carbon with a solution of sorbed species in a solvent 失效
标题翻译：用吸附物质溶于溶剂中的活性炭再生
公开(公告)号：US3965036A
公开(公告)日：1976-06-22
申请号：US491017
申请日：1974-07-23
申请人： Kenneth J. Himmelstein
发明人： Kenneth J. Himmelstein
IPC分类号： C01B31/08 , B01D15/06 , B01J21/20
CPC分类号： C01B31/087
摘要： Solvent regeneration of activated carbon on which a chemical species is sorbed is enhanced by the selective use of a regenerant solution containing a solvent for said chemical species and a predetermined concentration of the chemical species in solution. The stream of spent regenerant coming from the carbon is thereby made more concentrated in solute and easier to treat for separation of the solute and solvent.
摘要翻译：通过选择性地使用含有所述化学物质的溶剂的再生剂溶液和溶液中的化学物质的预定浓度来增强吸附有化学物质的活性炭的溶剂再生。因此，来自碳的废再生剂料流更多地浓缩在溶质中，并且更易于处理以分离溶质和溶剂。

9. 发明授权

US5599534A Reversible gel-forming composition for sustained delivery of bio-affecting substances, and method of use 失效
标题翻译：用于持续递送生物影响物质的可逆凝胶形成组合物及其使用方法
公开(公告)号：US5599534A
公开(公告)日：1997-02-04
申请号：US287694
申请日：1994-08-09
申请人： Kenneth J. Himmelstein , Cara L. Baustian
发明人： Kenneth J. Himmelstein , Cara L. Baustian
IPC分类号： A61K9/00 , A61K47/32 , A61K47/38 , A61K31/74 , A01N25/04 , A61K31/19
CPC分类号： A61K47/38 , A61K47/32 , A61K9/0014 , A61K9/0048 , Y10S514/912 , Y10S514/913 , Y10S514/914 , Y10S514/915
摘要： Reversibly gel-forming compositions for sustained delivery of bio-affecting substances are disclosed. The compositions exhibit significant changes in viscosity in response to changes in pH. The compositions contain relatively low concentrations of a stable combination of at least one pH-responsive gelling polymer and at least one other thermally nonresponsive polymer. The compositions are preferably formulated to include one or more therapeutic or diagnostic agents for administration as a liquid that will gel in situ or for topical application as a pre-formed gel.
摘要翻译：公开了用于持续递送生物影响物质的可逆凝胶形成组合物。组合物响应于pH的变化显示粘度的显着变化。组合物含有相对低浓度的至少一种pH响应性胶凝聚合物和至少一种其它热不响应聚合物的稳定组合。组合物优选配制成包括一种或多种用于作为液体施用的治疗剂或诊断剂，其将在原位凝胶或作为预先形成的凝胶局部施用。

10. 发明授权

US4489056A Acid anhydrides as rate controlling agent for the erosion of polymers which latter polymers have beneficial substances dispersed throughout their matrix or where the polymer matrix surrounds the beneficial substance 失效
标题翻译：酸酐作为用于聚合物侵蚀的速率控制剂，后者的聚合物具有分散在其整个基质中的有益物质或聚合物基质包围有益物质
公开(公告)号：US4489056A
公开(公告)日：1984-12-18
申请号：US393990
申请日：1982-06-30
申请人： Kenneth J. Himmelstein , Takeru Higuchi
发明人： Kenneth J. Himmelstein , Takeru Higuchi
IPC分类号： C08K5/00 , A01N25/10 , A61K9/20 , A61K9/22 , A61K47/34 , C08G65/00 , C08G67/04 , C08K5/09 , C08L59/00 , C08L67/00 , C08L71/00 , C08L71/02 , C08L73/02 , A61K9/26 , A61K9/52 , A61K31/74
CPC分类号： C08G67/04 , A01N25/10 , A61K9/2013 , A61K9/204 , C08L73/02
摘要： The invention relates to the use of an acid anhydride incorporated as a latentiated catalyst in poly(ortho ester) and other polymers such that upon exposure to aqueous environments the acid anhydride generates the corresponding acid which catalyzes the matrix erosion. The releasing rate of a loaded drug substance incorporated into or surrounded by the poly(ortho ester) or other polymers can be controlled in that the drug is released as the poly(ortho ester)s or other polymer is eroded by action of the acid anhydride incorporated therein.
摘要翻译：本发明涉及在聚（原酸酯）和其它聚合物中引入作为潜在催化剂的酸酐的用途，使得当暴露于水性环境时，酸酐产生催化基质侵蚀的相应酸。可以控制并入或聚合（原酸酯）或其它聚合物包围的负载药物的释放速率，因为当聚（原酸酯）或其它聚合物被酸酐的作用侵蚀时，药物被释放并入其中。

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