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目的全面解析黄连解毒汤(HJD)水煎自沉淀来源,并从分子热力学角度探讨HJD组方配伍中药间相互作用热力学参数及结合能力强弱,以期揭示中药复方水煎自沉淀形成机制。方法通过拆方研究,锁定产生水煎自沉淀的主要组方配伍;通过等温滴定量热技术(isothermal titration calorimetry,ITC)分别测定不同配伍中药相互作用过程中的能量和热力学参数变化,包括结合常数(Ka)、解离常数(Kd)、结合计量比(n)、焓变(ΔH)、熵变(ΔS)、吉布斯自由能变(ΔG),进而阐明不同组方配伍中药间结合能力的差异。结果拆方研究结果表明,能够产生明显自沉淀现象的配伍有黄芩-黄连、黄芩-黄柏,其中黄芩-黄连生成沉淀最明显,黄芩-黄柏次之;而黄芩-栀子、黄连-黄柏、黄柏-栀子、黄连-栀子配伍则未发现明显自沉淀生成。应用ITC分别考察黄芩-黄连、黄芩-黄柏、黄芩-栀子3种配伍关系,结果显示黄芩-栀子相互作用过程中能量变化显著低于黄芩-黄连和黄芩-黄柏相互作用的能量变化,3组的ΔH<0,-TΔS>0,ΔG<0,|ΔH|>|-TΔS|,均为焓驱动的自发反应过程;黄芩水煎液滴定黄连、黄柏、栀子水煎液的Ka依次为1.283×10~4、4.680×10~3、1.973×10~3,数值逐渐减小,反之K_d依次增大(7.794×10~(-5)、2.137×10~(-4)、5.068×10~(-4))。结论 HJD水煎自沉淀形成过程中,存在焓驱动非共价键结合的化学反应,而非简单的物理凝聚吸附沉淀;并且黄芩-黄连成分间结合力大于黄芩-黄柏成分间结合力,而黄芩-栀子间的相互作用极弱。
OBJECTIVE To comprehensively analyze the source of decoction of Huangjianjidudu Decoction (HJD) and to explore the thermodynamic parameters and the binding ability between HJD group and traditional Chinese medicine in terms of molecular thermodynamics, in order to reveal the mechanism of decoction and self-deposition of Chinese herbal compound decoction. Methods The main prescription of decoction and self-precipitation was locked through the study of demolition. The isothermal titration calorimetry (ITC) was used to determine the changes of energy and thermodynamic parameters during the interaction of different compatibility Chinese herbs, including the binding constant (Ka), dissociation constant (Kd), binding ratio (n), enthalpy change (ΔH), entropy change (ΔS) and Gibbs free energy change (ΔG) The difference. Results The results of demolition study showed that the combination of Scutellaria - Coptis and Scutellaria - Cortex Phellodendri can produce obvious self - precipitation phenomenon, of which Scutellaria - Coptis produce precipitation the most obvious, followed by Scutellaria - Cortex Phellodendri; and Scutellaria - Scutellaria, Coptis - - Gardenia, Coptis - Gardenia compatibility was found no significant self-precipitation. The results showed that the energy changes during the interaction between Scutellaria baicalensis and Zhiziyan were significantly lower than those from Scutellaria baicalensis-coptis and Scutellaria baicalensis Georgi, respectively The group of ΔH <0, -TΔS> 0, ΔG <0, | ΔH |> | -TΔS |, are enthalpy-driven spontaneous reaction process; Scutellaria decoction titration Coptis chinensis, Treats, Gardenia decoction of Ka The values of K_d increased gradually from 1.283 × 10 ~ 4, 4.80 × 10 ~ 3 and 1.973 × 10 ~ 3, while K_d increased (7.794 × 10 -5, 2.137 × 10 -4, 5.068 × 10 ~ (-4)). Conclusions In the process of decoction and self-precipitation of HJD, enthalpy drives the chemical reaction of non-covalent bond, rather than the simple physical cohesion and adsorption precipitation. The binding force between the components of Scutellaria baicalensis and Coptis is greater than that between Scutellaria baicalensis and Phellinus igniarius, - Gardenia interaction is very weak.