azane;(2S,3S,4S,5R)-2,3,4,5-tetrahydroxy-6-oxohexanoic acid | 514223-75-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: azane;(2S,3S,4S,5R)-2,3,4,5-tetrahydroxy-6-oxohexanoic acid
• CAS: 514223-75-7
• 化学式: C6H13NO7
• 分子量: 211.17
• InChiKey: PWTVFEDQZHXDCE-JSCKKFHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.12
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  136
• 氢给体数：
  6
• 氢受体数：
  8

文献信息

• Remote loading of sparingly water-soluble drugs into lipid vesicles
  申请人：ZONEONE PHARMA, INC.

  公开号：US10004759B2

  公开（公告）日：2018-06-26

  The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (<2 mg/mL). In the preferred embodiment the drug in the solubilizing agent is mixed with the liposomes in aqueous suspension so that the concentration of solubilizing agent is lowered to below its capacity to completely solubilize the drug. This results in the drug precipitating but remote loading is capability retained. The process is scalable and the resulting drug-loaded liposomes are characterized by a high drug-to-lipid ratios and predictable drug retention when the liposome encapsulated drug is administered in patients.

  本发明提供的脂质体组合物含有用于治疗危及生命的疾病的稀溶性药物。将药物封装在脂质体内的一种优选方法是远程或主动装载。然而，文献中描述的这种方法仅限于可自由溶于水溶液或溶解为水溶性复合物的药物。本发明描述了远程装载低水溶性（<2 mg/mL）药物的组合物和方法。在优选的实施方案中，溶解剂中的药物与水悬浮液中的脂质体混合，使溶解剂的浓度降低到低于其完全溶解药物的能力。这将导致药物沉淀，但远程负载能力得以保留。该工艺具有可扩展性，产生的药物负载脂质体的特点是药物与脂质的比率高，在患者服用脂质体包裹的药物时，药物保留率可预测。
• Remote loading of sparingly water-soluble drugs into liposomes
  申请人：ZONEONE PHARMA, INC.

  公开号：US10722467B2

  公开（公告）日：2020-07-28

  The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (<2 mg/mL). In the preferred embodiment the drug in the solubilizing agent is mixed with the liposomes in aqueous suspension so that the concentration of solubilizing agent is lowered to below its capacity to completely solubilize the drug. This results in the drug precipitating but remote loading capability is retained. The process is scalable and, in liposomes in which the lipid composition and remote loading agent are optimized, the resulting drug-loaded liposomes are characterized by a high drug-to-lipid ratios and prolonged drug retention when the liposome encapsulated drug is administered to a subject.

  本发明提供的脂质体组合物含有用于治疗危及生命的疾病的稀溶性药物。将药物封装在脂质体内的一种优选方法是远程或主动装载。通过将脂质体悬浮液与药物溶液共混，将药物远程装入含有跨膜电化学梯度的脂质体中，使化合物的中性形式自由进入脂质体并带静电，从而防止反向转移出脂质体。化合物在脂质体内部不断积聚，直到电化学梯度消失或所有药物都被包裹在脂质体中。然而，文献中描述的这一过程仅限于可在水溶液中自由溶解或溶解为水溶性复合物的药物。本发明描述了远程装载低水溶性（<2 mg/mL）药物的组合物和方法。在优选的实施方案中，溶解剂中的药物与水悬浮液中的脂质体混合，使溶解剂的浓度降低到低于其完全溶解药物的能力。这将导致药物沉淀，但远程装载能力得以保留。该工艺具有可扩展性，在脂质组成和远程装载剂都经过优化的脂质体中，所得到的药物负载脂质体的特点是药物与脂质的比率高，当将脂质体包裹的药物施用于受试者时，药物保留时间长。
• Method for drug loading in liposomes
  申请人：Gabizon A. Alberto

  公开号：US20050129753A1

  公开（公告）日：2005-06-16

  A liposome composition having a protonatable therapeutic agent entrapped in the form of a salt with an glucuronate anion is disclosed. Methods for preparing the composition using an ammonium ion transmembrane gradient having glucuronate as the counterion are also disclsoed. In one embodiment where the protonatable agent is doxorubicin, the method of the invention has comparable loading efficiency, faster release rate, without compromising the therapeutic efficacy compared to loading with an ammonium ion gradient having sulfate as the counterion.

  本发明公开了一种脂质体组合物，该组合物以带有葡萄糖醛酸阴离子的盐的形式夹带可质子化的治疗剂。还公开了使用以葡萄糖醛酸盐为反离子的铵离子跨膜梯度制备该组合物的方法。在一个可质子化的制剂为多柔比星的实施方案中，本发明的方法与以硫酸根为反离子的铵离子梯度法相比，具有可比的装载效率、更快的释放速率，且不影响疗效。
• Method for preparing liposome formulations with a predefined release profile
  申请人：Barenholz Yechezkel

  公开号：US20060165766A1

  公开（公告）日：2006-07-27

  The present invention provides a novel tool for designing a release profile of an active agent from a liposome in to which it is loaded. According to the invention, a method is provided for preparing a liposomal formulation for delivery of an active agent to a target, the release of said active agent from the liposome being designed to have a release profile in which the release is sustained for a time period to achieve an optimal effect of the active agent at said target, the method comprising preparing a liposomal formulation, wherein the liposome is loaded with said active agent and with a selected counter ion, the counter ion and the active agent interacting together to aggregate and/or to form a precipitate within the liposome, the counter ion being selected such that the release of the active agent from the liposome has said release profile.

  本发明提供了一种新型工具，用于设计活性剂从装载活性剂的脂质体中的释放曲线。根据本发明，提供了一种制备脂质体制剂的方法，该脂质体制剂用于将活性剂递送至目标物，所述活性剂从脂质体中的释放被设计成具有释放曲线，在该释放曲线中，活性剂的释放可持续一段时间，以达到活性剂在所述目标物中的最佳效果、该方法包括制备脂质体制剂，其中脂质体装载有所述活性剂和所选的反离子，反离子和活性剂相互作用，在脂质体内聚集和/或形成沉淀，反离子经过选择，使活性剂从脂质体的释放具有所述释放曲线。
• A METHOD FOR PREPARING LIPOSOME FORMULATIONS WITH A PREDEFINED RELEASE PROFILE
  申请人：YISSUM RESEARCH DEVELOPMENT COMPANYOF THE HEBREW UNIVERSITY OF JERUSALEM

  公开号：EP1429726A2

  公开（公告）日：2004-06-23