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1. 发明授权

US07879351B2 High delivery rates for lipid based drug formulations, and methods of treatment thereof 有权
标题翻译：基于脂质的药物制剂的高递送率及其治疗方法
公开(公告)号：US07879351B2
公开(公告)日：2011-02-01
申请号：US11398859
申请日：2006-04-06
申请人： Zhili Li , Lawrence T. Boni , Brian S. Miller , Vladimir Malinin , Xingong Li
发明人： Zhili Li , Lawrence T. Boni , Brian S. Miller , Vladimir Malinin , Xingong Li
IPC分类号： A61K9/127
CPC分类号： A61K9/0078 , A61K9/127 , A61K9/1617 , A61K9/5015 , A61K9/5123 , A61K31/7034 , A61K31/7036 , Y02A50/406 , Y02A50/473
摘要： Provided is a method of preparing lipid based drug formulations with low lipid/drug ratios using coacervation techniques. Also provided are methods of delivering such lipid based drug formulations at high delivery rates, and methods of treating patients with pulmonary diseases comprising administering such lipid based drug formulations.
摘要翻译：提供了使用凝聚技术制备具有低脂/药物比例的基于脂质的药物制剂的方法。还提供了以高递送速率递送这种基于脂质的药物制剂的方法，以及治疗患有肺部疾病的患者的方法，包括施用这种基于脂质的药物制剂。

2. 发明授权

US08802137B2 Sustained release of antiinfectives 有权
标题翻译：持续释放抗感染药
公开(公告)号：US08802137B2
公开(公告)日：2014-08-12
申请号：US12748756
申请日：2010-03-29
申请人： Lawrence T. Boni , Brian S. Miller , Vladimir Malinin , Xingong Li
发明人： Lawrence T. Boni , Brian S. Miller , Vladimir Malinin , Xingong Li
IPC分类号： A61K9/127 , A61K31/407 , A61K9/00 , A61K31/496 , A61K31/704 , A61K31/545 , A61K31/4709
CPC分类号： A61K47/28 , A61K9/0078 , A61K9/127 , A61K9/1277 , A61K31/407 , A61K31/4709 , A61K31/496 , A61K31/545 , A61K31/7036 , A61K31/704 , A61K45/06 , Y02A50/473
摘要： Provided are lipid antiinfective formulations substantially free of anionic lipids with a lipid to antiinfective ratio is about 1:1 to about 4:1, and a mean average diameter of less than about 1 μm. Also provided is a method of preparing a lipid antiinfective formulation comprising an infusion process. Also provided are lipid antiinfective formulations wherein the lipid to drug ratio is about 1:1 or less, about 0.75:1 or less, or about 0.50:1 or less prepared by an in line fusion process. The present invention also relates to a method of treating a patient with a pulmonary infection comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention. The present invention also relates to a method of treating a patient for cystic fibrosis comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention.
摘要翻译：提供基本上不含阴离子脂质的脂质抗感染制剂，其脂质与抗感染比为约1:1至约4:1，平均平均直径小于约1μm。还提供了制备包含输注方法的脂质抗感染制剂的方法。还提供了脂质抗感染制剂，其中通过在线融合方法制备的脂质与药物的比例为约1:1或更低，约0.75:1或更低，或约0.50:1或更低。本发明还涉及治疗患有肺部感染的患者的方法，其包括向患者施用治疗有效量的本发明的抗脂质抗感染药物。本发明还涉及一种治疗患者囊性纤维化的方法，其包括向患者施用治疗有效量的本发明的抗脂质抗感染制剂。

3. 发明申请

US20110159079A1 High Delivery Rates for Lipid Based Drug Formulations, and Methods of Treatment Thereof 审中-公开
标题翻译：基于脂质药物制剂的高递送率及其治疗方法
公开(公告)号：US20110159079A1
公开(公告)日：2011-06-30
申请号：US12983659
申请日：2011-01-03
申请人： Zhili Li , Lawrence T. Boni , Brian S. Miller , Vladimir Malinin , Xingong Li
发明人： Zhili Li , Lawrence T. Boni , Brian S. Miller , Vladimir Malinin , Xingong Li
IPC分类号： A61K9/127 , A61K47/44 , A61P31/00 , A61P11/00
CPC分类号： A61K9/0078 , A61K9/127 , A61K9/1617 , A61K9/5015 , A61K9/5123 , A61K31/7034 , A61K31/7036 , Y02A50/406 , Y02A50/473
摘要： Provided is a method of preparing lipid based drug formulations with low lipid/drug ratios using coacervation techniques. Also provided are methods of delivering such lipid based drug formulations at high delivery rates, and methods of treating patients with pulmonary diseases comprising administering such lipid based drug formulations.
摘要翻译：提供了使用凝聚技术制备具有低脂/药物比例的基于脂质的药物制剂的方法。还提供了以高递送速率递送这种基于脂质的药物制剂的方法，以及治疗患有肺部疾病的患者的方法，包括施用这种基于脂质的药物制剂。

4. 发明授权

US07718189B2 Sustained release of antiinfectives 有权
标题翻译：持续释放抗感染药
公开(公告)号：US07718189B2
公开(公告)日：2010-05-18
申请号：US11185448
申请日：2005-07-19
申请人： Lawrence T. Boni , Brian S. Miller , Vladimir Malinin , Xingong Li
发明人： Lawrence T. Boni , Brian S. Miller , Vladimir Malinin , Xingong Li
IPC分类号： A61K9/127
CPC分类号： A61K47/28 , A61K9/0078 , A61K9/127 , A61K9/1277 , A61K31/407 , A61K31/4709 , A61K31/496 , A61K31/545 , A61K31/7036 , A61K31/704 , A61K45/06 , Y02A50/473
摘要： Provided are lipid antiinfective formulations substantially free of anionic lipids with a lipid to antiinfective ratio is about 1:1 to about 4:1, and a mean average diameter of less than about 1 μm. Also provided is a method of preparing a lipid antiinfective formulation comprising an infusion process. Also provided are lipid antiinfective formulations wherein the lipid to drug ratio is about 1:1 or less, about 0.75:1 or less, or about 0.50:1 or less prepared by an in line fusion process. The present invention also relates to a method of treating a patient with a pulmonary infection comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention. The present invention also relates to a method of treating a patient for cystic fibrosis comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention.
摘要翻译：提供基本上不含阴离子脂质的脂质抗感染制剂，其脂质与抗感染比为约1:1至约4:1，平均平均直径小于约1μm。还提供了制备包含输注方法的脂质抗感染制剂的方法。还提供了脂质抗感染制剂，其中通过在线融合方法制备的脂质与药物的比例为约1:1或更低，约0.75:1或更低，或约0.50:1或更低。本发明还涉及治疗患有肺部感染的患者的方法，其包括向患者施用治疗有效量的本发明的抗脂质抗感染药物。本发明还涉及一种治疗患者囊性纤维化的方法，其包括向患者施用治疗有效量的本发明的抗脂质抗感染制剂。

5. 发明申请

US20100260829A1 Sustained Release of Antiinfectives 有权
标题翻译：持续释放抗感染药
公开(公告)号：US20100260829A1
公开(公告)日：2010-10-14
申请号：US12748756
申请日：2010-03-29
申请人： Lawrence Boni , Brian S. Miller , Vladimir Malinin , Xingong Li
发明人： Lawrence Boni , Brian S. Miller , Vladimir Malinin , Xingong Li
IPC分类号： A61K9/127 , A61K31/7036 , A61P31/04
CPC分类号： A61K47/28 , A61K9/0078 , A61K9/127 , A61K9/1277 , A61K31/407 , A61K31/4709 , A61K31/496 , A61K31/545 , A61K31/7036 , A61K31/704 , A61K45/06 , Y02A50/473
摘要： Provided are lipid antiinfective formulations substantially free of anionic lipids with a lipid to antiinfective ratio is about 1:1 to about 4:1, and a mean average diameter of less than about 1 μm. Also provided is a method of preparing a lipid antiinfective formulation comprising an infusion process. Also provided are lipid antiinfective formulations wherein the lipid to drug ratio is about 1:1 or less, about 0.75:1 or less, or about 0.50:1 or less prepared by an in line fusion process. The present invention also relates to a method of treating a patient with a pulmonary infection comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention. The present invention also relates to a method of treating a patient for cystic fibrosis comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention.
摘要翻译：提供基本上不含阴离子脂质的脂质抗感染制剂，其脂质与抗感染比为约1:1至约4:1，平均平均直径小于约1μm。还提供了制备包含输注方法的脂质抗感染制剂的方法。还提供了脂质抗感染制剂，其中通过在线融合方法制备的脂质与药物的比例为约1:1或更低，约0.75:1或更低，或约0.50:1或更低。本发明还涉及治疗患有肺部感染的患者的方法，其包括向患者施用治疗有效量的本发明的抗脂质抗感染药物。本发明还涉及一种治疗患者囊性纤维化的方法，其包括向患者施用治疗有效量的本发明的抗脂质抗感染制剂。

6. 发明申请

US20060073198A1 Sustained release of antifectives 有权
标题翻译：持续释放抗菌剂
公开(公告)号：US20060073198A1
公开(公告)日：2006-04-06
申请号：US11185448
申请日：2005-07-19
申请人： Lawrence Boni , Brian Miller , Vladimir Malinin , Xingong Li
发明人： Lawrence Boni , Brian Miller , Vladimir Malinin , Xingong Li
IPC分类号： A61K31/704 , A61K31/496 , A61K31/4709 , A61K9/127
CPC分类号： A61K47/28 , A61K9/0078 , A61K9/127 , A61K9/1277 , A61K31/407 , A61K31/4709 , A61K31/496 , A61K31/545 , A61K31/7036 , A61K31/704 , A61K45/06 , Y02A50/473
摘要： Provided are lipid antiinfective formulations substantially free of anionic lipids with a lipid to antiinfective ratio is about 1:1 to about 4:1, and a mean average diameter of less than about 1 μm. Also provided is a method of preparing a lipid antiinfective formulation comprising an infusion process. Also provided are lipid antiinfective formulations wherein the lipid to drug ratio is about 1:1 or less, about 0.75:1 or less, or about 0.50:1 or less prepared by an in line fusion process. The present invention also relates to a method of treating a patient with a pulmonary infection comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention. The present invention also relates to a method of treating a patient for cystic fibrosis comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention.
摘要翻译：提供基本上不含阴离子脂质的脂质抗感染制剂，其中脂质与抗感染比为约1:1至约4:1，平均平均直径小于约1μm。还提供了制备包含输注方法的脂质抗感染制剂的方法。还提供了脂质抗感染制剂，其中通过在线融合方法制备的脂质与药物的比例为约1:1或更低，约0.75:1或更低，或约0.50:1或更低。本发明还涉及治疗患有肺部感染的患者的方法，其包括向患者施用治疗有效量的本发明的抗脂质抗感染药物。本发明还涉及一种治疗患者囊性纤维化的方法，其包括向患者施用治疗有效量的本发明的抗脂质抗感染制剂。

7. 发明申请

US20070077290A1 High delivery rates for lipid based drug formulations, and methods of treatment thereof 有权
标题翻译：基于脂质的药物制剂的高递送率及其治疗方法
公开(公告)号：US20070077290A1
公开(公告)日：2007-04-05
申请号：US11398859
申请日：2006-04-06
申请人： Zhili Li , Lawrence Boni , Brian Miller , Vladimir Malinin , Xingong Li
发明人： Zhili Li , Lawrence Boni , Brian Miller , Vladimir Malinin , Xingong Li
IPC分类号： A61K31/7034 , A61K9/127
CPC分类号： A61K9/0078 , A61K9/127 , A61K9/1617 , A61K9/5015 , A61K9/5123 , A61K31/7034 , A61K31/7036 , Y02A50/406 , Y02A50/473
摘要： Provided is a method of preparing lipid based drug formulations with low lipid/drug ratios using coacervation techniques. Also provided are methods of delivering such lipid based drug formulations at high delivery rates, and methods of treating patients with pulmonary diseases comprising administering such lipid based drug formulations.
摘要翻译：提供了使用凝聚技术制备具有低脂/药物比例的基于脂质的药物制剂的方法。还提供了以高递送速率递送这种基于脂质的药物制剂的方法，以及治疗患有肺部疾病的患者的方法，包括施用这种基于脂质的药物制剂。

8. 发明申请

US20060062839A1 Efficient liposomal encapsulation under mild conditions 审中-公开
标题翻译：在温和条件下高效的脂质体包封
公开(公告)号：US20060062839A1
公开(公告)日：2006-03-23
申请号：US10500977
申请日：2003-01-08
申请人： Alla Polozova , Xingong Li , Walter Perkins
发明人： Alla Polozova , Xingong Li , Walter Perkins
IPC分类号： A61K9/127
CPC分类号： A61K9/1277 , A61K9/1278
摘要： A method for preparing liposomes containing at least one biologically active substance encapsulated therein under mild conditions comprises the following steps: (A) providing liposomes, wherein the liposomes are prepared by a method other than the instant method; (B) mixing the product of step (A) with a water-miscible organic solvent to form a gel or a liquid containing gel particles; and thereafter (C) (a) mixing the gel or liquid containing gel particles with aqueous medium V to directly form the liposomes containing the at least one biologically active substance encapsulated therein, (b) (i) mixing the gel or liquid containing gel particles with aqueous medium V to form a curd or curdy substance; and (ii) mixing the curd or curdy substance with aqueous medium W to directly form the liposomes containing the at least one biologically active substance encapsulated therein, or (c) (i) cooling the gel or liquid containing gel particles to form a waxy substance; and (ii) mixing the waxy substance with aqueous medium W to directly form the liposomes containing the at least one biologically active substance encapsulated therein; wherein the at least one biologically active substance is added in step (A), (B) or (C), and wherein aqueous media V and W are the same or different.
摘要翻译：一种在温和条件下包含至少一种包含其中的生物活性物质的脂质体的制备方法包括以下步骤：（A）提供脂质体，其中通过本方法以外的方法制备脂质体; （B）将步骤（A）的产物与水混溶性有机溶剂混合以形成凝胶或含有凝胶颗粒的液体; 然后（C）（a）将含有凝胶颗粒的凝胶或液体与水性介质V混合以直接形成包含至少一种生物活性物质的脂质体，（b）（i）将含有凝胶颗粒的凝胶或液体与水性介质V形成凝乳或卷曲物质; 和（ii）将凝乳或卷曲物质与水性介质W混合以直接形成包含其中的至少一种生物活性物质的脂质体，或（c）（i）冷却含有凝胶颗粒的凝胶或液体以形成蜡状物质 ; 和（ii）将蜡状物质与水性介质W混合以直接形成含有其中包封的至少一种生物活性物质的脂质体; 其中所述至少一种生物活性物质在步骤（A），（B）或（C）中加入，并且其中水性介质V和W相同或不同。

9. 发明申请

US20060058249A1 Efficient nucleic acid encapsulation into medium sized liposomes 审中-公开
标题翻译：将有效的核酸封装到中等大小的脂质体中
公开(公告)号：US20060058249A1
公开(公告)日：2006-03-16
申请号：US10500933
申请日：2003-01-08
申请人： Shangguan Tong , Xingong Li , Paul Meers , Walter Perkins
发明人： Shangguan Tong , Xingong Li , Paul Meers , Walter Perkins
IPC分类号： A61K48/00 , A61K9/127
CPC分类号： A61K9/127 , A61K9/1277 , A61K47/36 , C12N15/88
摘要： A method for preparing liposomes containing at least one nucleic acid encapsulated therein comprising the following steps: (A) mixing a gel or a liquid containing gel particles with aqueous medium Z1 to directly form the liposomes containing the at least one nucleic acid encapsulated therein; (B)(i) mixing a gel or a liquid containing gel particles with aqueous medium Z1 to form a curd or curdy substance; and (ii) mixing the curd or curdy substance with aqueous medium Z2 to directly form the liposomes containing the at least one nucleic acid encapsulated therein; or (C)(i) cooling a gel or a liquid containing gel particles to form a waxy substance; and (ii) mixing the waxy substance with aqueous medium Z1 to directly form the liposomes containing the at least one nucleic acid encapsulated therein; wherein said gel or liquid containing gel particles comprises at least one liposome-forming lipid, at least one fusogenic lipid, a water-miscible organic solvent and the at least one nucleic acid; wherein an amount of the at least one fusogenic lipid is at least 20% by weight of a lipid content of the gel or the liquid containing gel particles; and wherein the aqueous media Z1 and Z2 are the same or different.
摘要翻译：一种制备含有至少一种包封的核酸的脂质体的方法，包括以下步骤：（A）将凝胶或含有凝胶颗粒的液体与水性介质Z1混合以直接形成包含至少一种核酸的脂质体; （B）（i）将凝胶或含有凝胶颗粒的液体与水性介质Z1混合以形成凝乳或卷曲物质; 和（ii）将凝乳或卷曲物质与水性介质Z2混合以直接形成含有其中包封的至少一种核酸的脂质体; 或（C）（i）冷却凝胶或含有凝胶颗粒的液体以形成蜡状物质; 和（ii）将蜡质物质与水性介质Z1混合以直接形成包含其中包含至少一种核酸的脂质体; 其中所述含凝胶或液体的凝胶颗粒包含至少一种形成脂质体的脂质，至少一种融合脂质，与水可混溶的有机溶剂和所述至少一种核酸; 其中所述至少一种融合脂质的量为所述凝胶或含有凝胶颗粒的液体的脂质含量的至少20重量％并且其中水性介质Z1和Z2相同或不同。

10. 发明申请

US20090191259A1 Efficient liposomal encapsulation 审中-公开
标题翻译：高效的脂质体包封
公开(公告)号：US20090191259A1
公开(公告)日：2009-07-30
申请号：US10500932
申请日：2003-01-08
申请人： Xingong Li , Tong Shangguan , Alla Polozova , Paul R. Meers , Walter R. Perkins
发明人： Xingong Li , Tong Shangguan , Alla Polozova , Paul R. Meers , Walter R. Perkins
IPC分类号： A61K9/127 , A61K31/7088 , A61K38/02 , A61K31/711 , A61K39/00 , A61K39/395
CPC分类号： B01J13/02 , A61K9/1277 , A61K47/6911
摘要： The present invention concerns a method for preparing liposomes, said method comprising the following steps: (I) mixing at least one liposome-forming lipid, a water-miscible organic solvent and aqueous medium Y to form a gel or liquid containing gel particles without sonication; and thereafter (II) (a) mixing the gel or liquid containing gel particles with aqueous medium Z1 to directly form the liposomes; (b) (i) mixing the gel or liquid containing gel particles with aqueous medium Z1 to form a curd or curdy substance; and (ii) mixing the curd or curdy substance with aqueous medium Z2 to directly form the liposomes; or (c) (i) cooling the gel or liquid containing gel particles to form a waxy substance; and (ii) mixing the waxy substance with aqueous medium Z1 to directly form the liposomes; wherein aqueous media Y, Z1 and Z2 are the same or different.
摘要翻译：本发明涉及一种制备脂质体的方法，所述方法包括以下步骤：（I）将至少一种形成脂质体的脂质，水混溶性有机溶剂和水性介质Y混合以形成不含超声波处理的含有凝胶颗粒的凝胶或液体 ; 然后（II）（a）将含有凝胶颗粒的凝胶或液体与水性介质Z1混合以直接形成脂质体; （b）（i）将含有凝胶颗粒的凝胶或液体与水性介质Z1混合以形成凝乳或卷曲物质; 和（ii）将凝乳或卷曲物质与水性介质Z2混合以直接形成脂质体; 或（c）（i）冷却含有凝胶颗粒的凝胶或液体以形成蜡状物质; 和（ii）将蜡状物质与水性介质Z1混合以直接形成脂质体; 其中水性介质Y，Z1和Z2相同或不同。

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