-
公开(公告)号：US08389470B2
公开(公告)日：2013-03-05
申请号：US12985197
申请日：2011-01-05
CPC分类号： A61K47/22 , A61K9/0019 , A61K9/0073 , A61K9/0075 , A61K9/14 , A61K9/145 , A61K9/1617 , A61K9/1676 , A61K38/28 , A61K47/6949 , B82Y5/00 , C07D241/08 , C07K1/30 , C07K1/32 , C07K14/605 , C07K14/62 , Y10S514/866
摘要： Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal one or more impurities, from the peptide or protein. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration. The formulations include microparticles formed of (i) the active agent, which may be charged or neutral, and (ii) a transport enhancer that masks the charge of the agent and/or that forms hydrogen bonds with the target biological membrane in order to facilitate transport. In one embodiment, insulin is administered via the pulmonary delivery of microparticles comprising fumaryl diketopiperazine and insulin in its biologically active form. This method of delivering insulin results in a rapid increase in blood insulin concentration that is comparable to the increase resulting from intravenous delivery.
摘要翻译： 提供了通过将肽或蛋白质掺入二酮哌嗪或竞争性络合剂来促进从肽或蛋白质中去除一种或多种杂质来纯化肽和蛋白质的方法。 提供制剂和方法用于改善活性剂在生物膜上的转运，导致例如血药剂浓度的快速增加。 制剂包括由（i）可以带电或中性的活性剂形成的微粒，和（ii）掩蔽试剂的电荷和/或与靶生物膜形成氢键的运输增强剂，以便于 运输。 在一个实施方案中，胰岛素经由包含富马酰二酮基哌嗪和胰岛素的微粒的肺部递送以其生物活性形式施用。 这种递送胰岛素的方法导致血浆胰岛素浓度的快速增加，其与由静脉内递送产生的增加相当。
-
公开(公告)号：US20110105391A1
公开(公告)日：2011-05-05
申请号：US12985197
申请日：2011-01-05
CPC分类号： A61K47/22 , A61K9/0019 , A61K9/0073 , A61K9/0075 , A61K9/14 , A61K9/145 , A61K9/1617 , A61K9/1676 , A61K38/28 , A61K47/6949 , B82Y5/00 , C07D241/08 , C07K1/30 , C07K1/32 , C07K14/605 , C07K14/62 , Y10S514/866
摘要： Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal one or more impurities, from the peptide or protein. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration. The formulations include microparticles formed of (i) the active agent, which may be charged or neutral, and (ii) a transport enhancer that masks the charge of the agent and/or that forms hydrogen bonds with the target biological membrane in order to facilitate transport. In one embodiment, insulin is administered via the pulmonary delivery of microparticles comprising fumaryl diketopiperazine and insulin in its biologically active form. This method of delivering insulin results in a rapid increase in blood insulin concentration that is comparable to the increase resulting from intravenous delivery.
摘要翻译： 提供了通过将肽或蛋白质掺入二酮哌嗪或竞争性络合剂来促进从肽或蛋白质中去除一种或多种杂质来纯化肽和蛋白质的方法。 提供制剂和方法用于改善活性剂在生物膜上的转运，导致例如血药剂浓度的快速增加。 制剂包括由（i）可以带电或中性的活性剂形成的微粒，和（ii）掩蔽试剂的电荷和/或与靶生物膜形成氢键的运输增强剂，以便于 运输。 在一个实施方案中，胰岛素经由包含富马酰二酮基哌嗪和胰岛素的微粒的肺部递送以其生物活性形式施用。 这种递送胰岛素的方法导致血浆胰岛素浓度的快速增加，其与由静脉内递送产生的增加相当。
-
公开(公告)号：US20100086609A1
公开(公告)日：2010-04-08
申请号：US12635380
申请日：2009-12-10
IPC分类号： A61K38/28 , A61K38/26 , A61K31/496 , A61K31/495 , A61K9/14
CPC分类号： A61K47/22 , A61K9/0019 , A61K9/0073 , A61K9/0075 , A61K9/14 , A61K9/145 , A61K9/1617 , A61K9/1676 , A61K38/28 , A61K47/6949 , B82Y5/00 , C07D241/08 , C07K1/30 , C07K1/32 , C07K14/605 , C07K14/62 , Y10S514/866
摘要： Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal one or more impurities, from the peptide or protein. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration. The formulations include microparticles formed of (i) the active agent, which may be charged or neutral, and (ii) a transport enhancer that masks the charge of the agent and/or that forms hydrogen bonds with the target biological membrane in order to facilitate transport. In one embodiment, insulin is administered via the pulmonary delivery of microparticles comprising fumaryl diketopiperazine and insulin in its biologically active form. This method of delivering insulin results in a rapid increase in blood insulin concentration that is comparable to the increase resulting from intravenous delivery.
摘要翻译： 提供了通过将肽或蛋白质掺入二酮哌嗪或竞争性络合剂来促进从肽或蛋白质中去除一种或多种杂质来纯化肽和蛋白质的方法。 提供制剂和方法用于改善活性剂在生物膜上的转运，导致例如血药剂浓度的快速增加。 制剂包括由（i）可以带电或中性的活性剂形成的微粒，和（ii）掩蔽试剂的电荷和/或与靶生物膜形成氢键的运输增强剂，以便于 运输。 在一个实施方案中，胰岛素经由包含富马酰二酮基哌嗪和胰岛素的微粒的肺部递送以其生物活性形式施用。 这种递送胰岛素的方法导致血浆胰岛素浓度的快速增加，其与由静脉内递送产生的增加相当。
-
公开(公告)号：US20080248999A1
公开(公告)日：2008-10-09
申请号：US12062355
申请日：2008-04-03
申请人： Solomon S. Steiner
发明人： Solomon S. Steiner
CPC分类号： A61K45/06 , A61K9/0019 , A61K38/28 , A61K47/183 , A61K2300/00
摘要： A combined insulin and amylin and/or GLP-1 mimetic formulation has been developed wherein the pH of the insulin is decreased so that the amylin and/or GLP-1 remains soluble when mixed together with the insulin. In the preferred embodiment, a bolus insulin is administered by injection before breakfast, providing adequate bolus insulin levels to cover the meal, without producing hypoglycemia after the meal. This can be combined with an adequate basal insulin for 24 hours. Lunch and dinner can be covered by two bolus injections of the insulin and amylin and/or GLP-1 mimetic combination. A GLP-1 mimetic may be combined with either rapid acting or basal insulin formulations. As a result, a patient using the combination formulation therapy may only need to inject half as many times per day.
摘要翻译： 已经开发了胰岛素和胰岛淀粉样多肽和/或GLP-1模拟组合物，其中胰岛素的pH降低，使得当与胰岛素一起混合时，胰岛淀粉样多肽和/或GLP-1保持可溶。 在优选实施方案中，在早餐之前通过注射施用推注胰岛素，提供足够的推注胰岛素水平以覆盖膳食，而不会在饭后产生低血糖。 这可以与足够的基础胰岛素组合24小时。 午餐和晚餐可以通过两次快速注射胰岛素和胰岛淀粉样多肽和/或GLP-1模拟组合来覆盖。 GLP-1模拟物可以与快速作用或基础胰岛素制剂组合。 因此，使用组合制剂治疗的患者可能只需要每天注射一半次。
-
公开(公告)号：US20080039365A1
公开(公告)日：2008-02-14
申请号：US11695562
申请日：2007-04-02
申请人： Solomon S. Steiner , Roderike Pohl
发明人： Solomon S. Steiner , Roderike Pohl
IPC分类号： A61K38/28 , A61K31/385 , A61K31/185 , A61K31/19 , A61K36/02
CPC分类号： A61K38/28 , A61K31/185 , A61K31/19 , A61K31/385 , A61K2300/00
摘要： A combined rapid acting-long acting insulin formulation has been developed wherein the pH of the rapid acting insulin is decreased so that the long acting glargine remains soluble when they are mixed together. In the preferred embodiment, this injectable basal bolus insulin is administered before breakfast, provides adequate bolus insulin levels to cover the meal, does not produce hypoglycemia after the meal and provides adequate basal insulin for 24 hours. Lunch and dinner can be covered by two bolus injections of a fast acting, or a rapid acting or a very rapid acting insulin. As a result, a patient using intensive insulin therapy should only inject three, rather than four, times a day. Experiments have been performed to demonstrate the importance of the addition of specific acids to hexameric insulin to enhance speed and amount of absorption and preserve bioactivity following dissociation into the monomeric form by addition of a chelator such as EDTA. As shown by the examples, the preferred acids are aspartic, glutamic and citric acid. These are added in addition to a chelator, preferably ethylenediaminetetraacetic acid (EDTA). The results show that the citric acid formulation was more effective at dropping the blood glucose rapidly than the identical rapid acting formulation prepared with HCl in swine. Charge masking by the polyacid appears to be responsible for rapid insulin absorption. EDTA was not effective when used with adipic acid, oxalic acid or HCl at hastening the absorption of insulin. These results confirm the results seen in clinical subjects and patients with diabetes treated with the rapid acting insulin in combination with citric acid and EDTA.
摘要翻译： 已经开发了组合的快速作用长效胰岛素制剂，其中快速作用的胰岛素的pH降低，使得长效甘精胰醇混合在一起时仍然是可溶的。 在优选的实施方案中，这种可注射的基础推注胰岛素在早餐前施用，提供足够的推注胰岛素水平以覆盖膳食，在餐后不产生低血糖并提供足够的基础胰岛素24小时。 午餐和晚餐可以通过快速作用或快速作用或非常快速作用的胰岛素的两次快速注射来覆盖。 因此，使用强化胰岛素治疗的患者每天只能注射三次，而不是四次。 已经进行了实验以证明向六聚胰岛素中加入特定酸的重要性，以通过加入螯合剂如EDTA解离成单体形式来提高速度和吸收量并保持生物活性。 如实施例所示，优选的酸是天冬氨酸，谷氨酸和柠檬酸。 除了螯合剂，优选乙二胺四乙酸（EDTA）之外还加入它们。 结果表明，柠檬酸配方比在猪中用HCl制备的相同的快速作用制剂快速降低血糖。 多酸的电荷掩蔽似乎是快速胰岛素吸收的原因。 当与己二酸，草酸或HCl一起使用以加速胰岛素的吸收时，EDTA无效。 这些结果证实了临床受试者和用快速作用胰岛素与柠檬酸和EDTA组合治疗的糖尿病患者的结果。
-
公开(公告)号：US07279457B2
公开(公告)日：2007-10-09
申请号：US11077604
申请日：2005-03-11
申请人： Roderike Pohl , Solomon S. Steiner
发明人： Roderike Pohl , Solomon S. Steiner
CPC分类号： A61K9/006 , A61K9/0019 , A61K9/0056 , A61K38/28 , Y10S514/866 , Y10S514/951 , Y10S514/953 , Y10S514/959
摘要： Drug formulations for systemic drug delivery with improved stability and rapid onset of action are described herein. The formulations may be administered via buccal administration, sublingual administration, pulmonary delivery, nasal administration, subcutaneous administration, rectal administration, vaginal administration, or ocular administration. In the preferred embodiments, the formulations are administered sublingually or via subcutaneous injection. The formulations contain an active agent and one or more excipients, selected to increase the rate of dissolution. In the preferred embodiment, the drug is insulin, and the excipients include a metal chelator such as EDTA and an acid such as citric acid. Following administration, these formulations are rapidly absorbed by the oral mucosa when administered sublingually and are rapidly absorbed into the blood stream when administered by subcutaneous injection. In one embodiment, the composition is in the form of a dry powder. In another embodiment, the composition is in the form of a film, wafer, lozenge, capsule, or tablet. In a third embodiment, a dry powdered insulin is mixed with a diluent containing a pharmaceutically acceptable carrier, such as water or saline, a metal chelator such as EDTA and an acid such as citric acid. Devices for storing and mixing these formulations are also described.
摘要翻译： 本文描述了具有改善的稳定性和快速起效的全身药物递送的药物制剂。 制剂可以通过口腔给药，舌下给药，肺部输送，鼻内给药，皮下给药，直肠给药，阴道给药或眼部给药来施用。 在优选的实施方案中，制剂是舌下给药或通过皮下注射给药。 制剂含有活性剂和一种或多种赋形剂，其被选择以增加溶解速率。 在优选的实施方案中，药物是胰岛素，赋形剂包括金属螯合剂如EDTA和酸如柠檬酸。 给药后，这些制剂在舌下施用时被口腔粘膜快速吸收，并且当通过皮下注射给药时，其迅速地被吸收到血液流中。 在一个实施方案中，组合物为干粉的形式。 在另一个实施方案中，组合物为薄膜，晶片，锭剂，胶囊或片剂的形式。 在第三个实施方案中，将干粉状胰岛素与含有药学上可接受的载体如水或盐水，金属螯合剂如EDTA和酸如柠檬酸的稀释剂混合。 还描述了用于储存和混合这些制剂的装置。
-
37.发明授权公开(公告)号：US06444226B1
公开(公告)日：2002-09-03
申请号：US09606468
申请日：2000-06-29
IPC分类号： A61K914
CPC分类号： A61K47/22 , A61K9/0019 , A61K9/0073 , A61K9/0075 , A61K9/14 , A61K9/145 , A61K9/1617 , A61K9/1676 , A61K38/28 , A61K47/6949 , B82Y5/00 , C07D241/08 , C07K1/30 , C07K1/32 , C07K14/605 , C07K14/62 , Y10S514/866
摘要： Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal one or more impurities, i.e. undesirable components, from the peptide or protein. In a preferred embodiment, a peptide, such as insulin, containing one or more impurities, e.g., zinc ions, is entrapped in diketopiperazine to form a precipitate of peptide/diketopiperazine/impurity, which is then washed with a solvent for the impurity to be removed, which is a nonsolvent for the diketopiperazine and a nonsolvent for the peptide. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration. The formulations include microparticles formed of (i) the active agent, which may be charged or neutral, and (ii) a transport enhancer that masks the charge of the agent and/or that forms hydrogen bonds with the target biological membrane in order to facilitate transport. In a preferred embodiment, insulin is administered via the pulmonary delivery of microparticles comprising fumaryl diketopiperazine and insulin in its biologically active form. The charge on the insulin molecule is masked by hydrogen bonding it to the diketopiperazine, thereby enabling the insulin to pass through the target membrane. This method of delivering insulin results in a rapid increase in blood insulin concentration that is comparable to the increase resulting from intravenous delivery.
摘要翻译： 提供了通过将肽或蛋白质掺入二酮哌嗪或竞争性络合剂来促进从肽或蛋白质中去除一种或多种杂质（即不合需要的组分）来纯化肽和蛋白质的方法。 在优选的实施方案中，将包含一种或多种杂质（例如锌离子）的肽例如包被在二酮哌嗪中以形成肽/二酮哌嗪/杂质的沉淀物，然后用溶剂洗涤以使杂质为 去除，这是二酮哌嗪的非溶剂和肽的非溶剂。 提供制剂和方法用于改善活性剂在生物膜上的转运，导致例如血药剂浓度的快速增加。 制剂包括由（i）可以带电或中性的活性剂形成的微粒，和（ii）掩蔽试剂的电荷和/或与靶生物膜形成氢键的运输增强剂，以便于 运输。 在优选的实施方案中，胰岛素经由包含富马酰二酮哌嗪和胰岛素的微粒的肺部递送以其生物活性形式施用。 胰岛素分子上的电荷被氢键键合到二酮哌嗪上，从而使胰岛素能够通过靶膜。 这种递送胰岛素的方法导致血浆胰岛素浓度的快速增加，其与由静脉内递送产生的增加相当。
-
公开(公告)号：US20120087985A1
公开(公告)日：2012-04-12
申请号：US13253410
申请日：2011-10-05
申请人： Solomon S. Steiner
发明人： Solomon S. Steiner
CPC分类号： A61K38/26 , A61K9/0019 , A61K9/10 , A61K9/1617
摘要： Disclosed herein are a class of small molecules, referred to as Small Peptide Sequences (SPS), that can stabilize biomolecules, particles containing the SPS and biomolecules, and compositions and methods of making the particles. The SPS are composed solely of amino acids common to humans and too small to trigger an immunological response (typically less than seven amino acids in total) and which will self assemble into particles sufficiently small to stay in liquid suspension at a first pH, typically a non-physiological pH, but which dissociate, releasing the biomolecule entrapped therein into solution, at a second pH, typically a physiological pH. The particles contain a SPS and a biomolecule, wherein the biomolecule is entrapped with the particle, immobilized on the surface of the particle, or combinations thereof. The particle releases the biomolecule upon contact with physiological fluids.
摘要翻译： 本文公开了一类称为小肽序列（SPS）的小分子，其可以稳定生物分子，含有SPS和生物分子的颗粒，以及制备颗粒的组合物和方法。 SPS仅由人类常见的氨基酸组成，太小而不能触发免疫应答（通常总共小于7个氨基酸），并且其将自我组装成足够小的颗粒，以在第一pH下停留在液体悬浮液中，通常为 非生理pH，但其解离，在第二个pH（通常为生理pH）下将包埋在其中的生物分子释放到溶液中。 颗粒含有SPS和生物分子，其中生物分子被捕获，固定在颗粒的表面上，或其组合。 颗粒在与生理液体接触时释放生物分子。
-
公开(公告)号：US07943178B2
公开(公告)日：2011-05-17
申请号：US12635380
申请日：2009-12-10
CPC分类号： A61K47/22 , A61K9/0019 , A61K9/0073 , A61K9/0075 , A61K9/14 , A61K9/145 , A61K9/1617 , A61K9/1676 , A61K38/28 , A61K47/6949 , B82Y5/00 , C07D241/08 , C07K1/30 , C07K1/32 , C07K14/605 , C07K14/62 , Y10S514/866
摘要： Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal one or more impurities, from the peptide or protein. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration. The formulations include microparticles formed of (i) the active agent, which may be charged or neutral, and (ii) a transport enhancer that masks the charge of the agent and/or that forms hydrogen bonds with the target biological membrane in order to facilitate transport. In one embodiment, insulin is administered via the pulmonary delivery of microparticles comprising fumaryl diketopiperazine and insulin in its biologically active form. This method of delivering insulin results in a rapid increase in blood insulin concentration that is comparable to the increase resulting from intravenous delivery.
摘要翻译： 提供了通过将肽或蛋白质掺入二酮哌嗪或竞争性络合剂来促进从肽或蛋白质中去除一种或多种杂质来纯化肽和蛋白质的方法。 提供制剂和方法用于改善活性剂在生物膜上的转运，导致例如血药剂浓度的快速增加。 制剂包括由（i）可以带电或中性的活性剂形成的微粒，和（ii）掩蔽试剂的电荷和/或与靶生物膜形成氢键的运输增强剂，以便于 运输。 在一个实施方案中，胰岛素经由包含富马酰二酮基哌嗪和胰岛素的微粒的肺部递送以其生物活性形式施用。 这种递送胰岛素的方法导致血浆胰岛素浓度的快速增加，其与由静脉内递送产生的增加相当。
-
公开(公告)号：US07833550B2
公开(公告)日：2010-11-16
申请号：US11842863
申请日：2007-08-21
CPC分类号： A61K31/4402 , A61K9/0043 , A61K9/145 , A61K9/146 , A61K9/1617 , A61K9/1629 , A61K9/19 , A61K31/55
摘要： Dry powder formulations of drugs such as antihistamine for nasal administration are provided where the drug is retained in the nasal cavity, and systemic side effects minimized or eliminated, through the selection of a narrow particle size range, between approximately 10 and 20 microns in diameter. In a preferred embodiment wherein the drug is an antihistamine, retention of the antihistamine at the nasal mucosa is improved and the bitter aftertaste associated with liquid antihistamine formulations significantly reduced. By making a dry powder formulation of an antihistamine (e.g., azelastine) having an average particle size of between 10 and 20 microns, the antihistamine is restricted primarily to the desired target organ, the nasal mucosa. Because the active ingredient stays in the nasal region, a lower dose can be used to achieve the same desired effect. As demonstrated by the examples, this lower dose reduces the incidence of somnolence, and because the active ingredient remains at the target organ and does not accumulate in the back of the throat and mouth, this formulation does not impart a bitter taste.
-
-
-
-
-
-
-
-
-
搜索结果
66 条记录 (耗时 0.031 秒)
