benzenesulfonic acid;[(2R,3R,4S,5R,6R)-2-[(2S,3S,4R,5R)-3,4-disulfooxy-2,5-bis(sulfooxymethyl)oxolan-2-yl]oxy-3,5-disulfooxy-6-(sulfooxymethyl)oxan-4-yl] hydrogen sulfate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: benzenesulfonic acid;[(2R,3R,4S,5R,6R)-2-[(2S,3S,4R,5R)-3,4-disulfooxy-2,5-bis(sulfooxymethyl)oxolan-2-yl]oxy-3,5-disulfooxy-6-(sulfooxymethyl)oxan-4-yl] hydrogen sulfate
• 化学式: C18H28O38S9
• 分子量: 1141.0
• InChiKey: NKEALCQUEGGIMJ-AKSHDPDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.85
• 重原子数：
  65
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  666
• 氢给体数：
  9
• 氢受体数：
  38

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。
• REMOTE LOADING OF SPARINGLY WATER-SOLUBLE DRUGS INTO LIPOSOMES
  申请人：Zoneone Pharma, Inc.

  公开号：EP2950784A2

  公开（公告）日：2015-12-09
• REMOTE LOADING OF SPARINGLY WATER-SOLUBLE DRUGS INTO LIPID VESICLES
  申请人：Zoneone Pharma, Inc.

  公开号：EP3177269A1

  公开（公告）日：2017-06-14
• TRANSFORMATION OF DRUG CYCLODEXTRIN COMPLEX COMPOSITIONS INTO COMPOSITIONS OF MIXTURES OF LIPID VESICLE ENCAPSULATED DRUG AND CYCLODEXTRIN DRUG COMPLEXES
  申请人：Zoneone Pharma, Inc.

  公开号：US20140220112A1

  公开（公告）日：2014-08-07

  Sparingly water-soluble agents can be formulated as cyclodextrin complexes, however, these water-soluble drug-cyclodextrin complexes dissociate when the complex is administered into patients. The dilution of the complex in the patient leads to the drug being released from the complex, so the drug is not effectively targeted. In contrast, drugs encapsulated in the aqueous core of a lipid vesicles are not released when the liposome is diluted in blood. This invention describes compositions and methods whereby cyclodextrin or polyanionic beta-cyclodextrin drug-complexes are mixed with a preformed liposome containing the amine salts of an acidic compound. This results in the drug cyclodextrin complex being transferred into the liposome where it is stably retained. The liposome-encapsulated drug can then be injected into a patient.