4-乙酰基大黄酸 | 875535-36-7

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 中文名称: 4-乙酰基大黄酸
• 中文别名: 双醋瑞因杂质(CAS:875535-36-7和CAS:875535-35-6)
• 英文名称: 4-Acetyl Rhein
• 英文别名: 4-acetyloxy-5-hydroxy-9,10-dioxoanthracene-2-carboxylic acid
• CAS: 875535-36-7
• 化学式: C₁₇H₁₀O₇
• 分子量: 326.262
• InChiKey: FRIXMWPJYKVOCV-UHFFFAOYSA-N

物化性质

• 熔点：
  235-237°C
• 沸点：
  635.5±55.0 °C(Predicted)
• 密度：
  1.571±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（轻微）、甲醇（轻微、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  双醋瑞因 在 hydroxypropyl-β-cyclodextrin 作用下， 以 aq. phosphate buffer 、 二甲基亚砜 为溶剂， 生成 大黄酸 、 4-乙酰基大黄酸 、 双醋瑞因杂质
  参考文献：
  名称：

  Spectroscopic characterization of both aqueous and solid-state diacerhein/hydroxypropyl-β-cyclodextrin inclusion complexes

  摘要：

  Diacerhein, a poorly water soluble antirheumatic prodrug, was spectroscopically characterized to form inclusion complexes with hydroxypropyl-E-cyclodextrin (HP beta CD) in both aqueous solution and in solid phase. Complexation with the hydrophilic carriers was used to improve the solubility and dissolution rate of the compound. The kinetics of the prodrug degradation to the active rhein in aqueous buffer solution were also investigated as a function of HP beta CD concentration. The solid complexes prepared by different methods such as physical mixture, kneading, co-evaporation method and freeze dried method in 1:1 M ratio, were characterized by DSC and FTIR. The dissolution profiles of solid complexes were determined and compared with diacerhein alone and their physical mixture, in the simulated intestinal fluid at 37 C. The accurate molecular spectroscopic characterization of diacerhein in the presence of different amounts of aqueous cyclodextrins was essential to determine the correct binding constants for the diacerhein/HP beta CD system. The binding constants were also validated by UV spectrometry and HPLC procedure in order to compare the values from the different methods. Higuchi-Connors phase solubility method has proved not suitable when either the free or/and the complexed prodrug degrade in aqueous solution. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.saa.2014.02.055

文献信息

• Spectroscopic characterization of both aqueous and solid-state diacerhein/hydroxypropyl-β-cyclodextrin inclusion complexes
  作者：Stefania Petralito、Iacopo Zanardi、Romina Spera、Adriana Memoli、Valter Travagli

  DOI：10.1016/j.saa.2014.02.055

  日期：2014.6

  Diacerhein, a poorly water soluble antirheumatic prodrug, was spectroscopically characterized to form inclusion complexes with hydroxypropyl-E-cyclodextrin (HP beta CD) in both aqueous solution and in solid phase. Complexation with the hydrophilic carriers was used to improve the solubility and dissolution rate of the compound. The kinetics of the prodrug degradation to the active rhein in aqueous buffer solution were also investigated as a function of HP beta CD concentration. The solid complexes prepared by different methods such as physical mixture, kneading, co-evaporation method and freeze dried method in 1:1 M ratio, were characterized by DSC and FTIR. The dissolution profiles of solid complexes were determined and compared with diacerhein alone and their physical mixture, in the simulated intestinal fluid at 37 C. The accurate molecular spectroscopic characterization of diacerhein in the presence of different amounts of aqueous cyclodextrins was essential to determine the correct binding constants for the diacerhein/HP beta CD system. The binding constants were also validated by UV spectrometry and HPLC procedure in order to compare the values from the different methods. Higuchi-Connors phase solubility method has proved not suitable when either the free or/and the complexed prodrug degrade in aqueous solution. (C) 2014 Elsevier B.V. All rights reserved.