摘要
目的:比较3种非离子型表面活性剂聚山梨酯80(Tween-80)、泊洛沙姆188(P188)、聚乙二醇400(PEG 400)对清开灵注射液(QKL)八混液中间体中3种难溶性成分黄芩苷(BCL)、胆酸(CA)、猪去氧胆酸(HA)的增溶效果。方法:根据BCL在水、缓冲液、QKL 3类溶剂中及CA、HA在QKL中的溶解情况,分别在3类溶剂中加入3种非离子型表面活性剂,采用HPLC法测定难溶性成分的含量,以绝对增溶度(ΔS)和相对增溶率(RS)为评价指标来考察增溶效果。结果:Tween-80、PEG400、P188 3种增溶剂对水中的BCL均有一定增溶作用,其溶解度随增溶剂浓度增加呈线性增大。Tween-80、P188、PEG 400浓度均为1.0%时,其RS分别为1.22、0.38、0.72,在水中对BCL的增溶能力大小排序Tween-80>PEG 400>P188;BCL在一定p H值的缓冲液中的溶解度大幅提高,Tween-80对BCL的增溶效果更佳,相比在水溶液中其ΔS大为增加,而RS却较在水中大为降低(RS<0.2);在QKL八混液(指含有胆酸、猪去氧胆酸、水牛角、珍珠母、黄芩苷、栀子、板蓝根、金银花8种中药成分的清开灵注射液半成品)中间体中,相对于p H的影响,增溶剂的浓度对溶解度的影响较弱;Tween-80对CA、HA的RS高于BCL。结论:3种增溶剂对3类难溶性成分在不同的溶剂中均具有增溶作用,且随着浓度升高增溶作用逐步提高;3种增溶剂对QKL八混液中间体中难溶性成分的增溶能力不尽一致,在选择增溶剂时应进行优化,且因p H对部分难溶性成分的溶解度影响较大,在增溶时注意调节适宜的p H;增溶剂对难溶性成分的增溶效能与该成分的log P值有关。
Objective： Qingkailing Injection Intermediate which contains three insoluble ingredients（ baicalin,cholic acid and hyodeoxycholic acid）, were used as research carriers. Polysorbate 80（ Tween-80）, Poloxamer 188（ P188） and polyethylene glycol 400（ PEG400）,a total of three non-ionic surfactants were taken as solubilizer,and this paper is aimed to compare the solubilization efficiency. Method： According to the solubility of BCL in three classes of solvent（ water、buffer and QKL） and the dissolution of CA and HA in QKL,the Absolute Solubilization Quantity（ ΔS） and Relative Solubilization Rate（ RS） as the evaluation index to study the solubilization effect,the contents of insoluble ingredients after solubilization by three non-ionic surfactants were determined by HPLC. Result： Three solubilizers showed the effect of solubilization on the BCL and the solubility increase mainly in linear way with the growth of the concentration of the solubilizer. When the concentration of Tween-80,P188 and PEG400 were 1%,the RS were 1. 22,0. 38 and 0. 7 respectively; the order of solubilization efficiency of among the three kinds of non-ionic surfactants was following： Tween-80 PEG400 P188; the solubility of BCL increased remarkably with buffer of a certain p H value,The ΔS of BCL was greatly increased by Tween-80 in water,while the RS was greatly reduced（ RS 0. 2）; In Qingkailing Injection Intermediate, The effect of the concentration of the solvent on the solubility of the solvent is weaker than that of the p H. The effect of Tween-80 was higher than that of CA and HA to BCL. Conclusion： In different solvents,three solubilizers had an effect of solubilization on the insoluble ingredients,and solubilization efficiency was positively correlated with the concentration of the solubilizer. The optimization should be carried out when selecting solubilizer. The p H of solvents had a greater impact on the solubility of the insoluble ingredients and suggested that attention should be paid to p H adjustment in the solubilization of insoluble ingredients. Solubilization efficiency is correlation relationship with the log P of insoluble ingredients.
出处
《中国现代中药》
CAS
2016年第2期213-218,共6页
Modern Chinese Medicine
基金
国家自然科学基金(81001646)
国家中医药管理局中医药行业科研专项(200708006)
