Chistyachenko Yulia S, Dushkin Alexandr V, Polyakov Nikolay E, Khvostov Mikhail V, Tolstikova Tatyana G, Tolstikov Genrikh A, Lyakhov Nikolay Z
Institute of Solid State Chemistry and Mechanochemistry , Novosibirsk , Russia .
Drug Deliv. 2015 May;22(3):400-7. doi: 10.3109/10717544.2014.884655. Epub 2014 Feb 12.
Inclusion complexes of salicylic acid (SA) and acetylsalicylic acid (aspirin, ASA) with polysaccharide arabinogalactan (AG) from larch wood Larix sibirica and Larix gmelinii were synthesized using mechanochemical technology. In the present study, we have investigated physicochemical properties of the synthesized complexes in solid state and in aqueous solutions as well as their anti-aggregation and ulcerogenic activity. The evidence of the complexes formation was obtained by nuclear magnetic resonance (NMR) relaxation technique. It was shown that in aqueous solution the molecules of SA and ASA are in fast exchange between the complex with AG macromolecules and solution. The stability constant of aspirin complex was calculated. It was shown that mechanochemically synthesized complexes are more stable when compared to the complex obtained by mixing solutions of the components. Complexes of ASA show two-fold increase of anti-platelet effect. It allows to reduce the dose of the antithrombotic drug and its ulcerogenic activity. These results substantiate the possibility to design new preparations on the basis of ASA with increased activity and safety.
采用机械化学技术合成了水杨酸(SA)和乙酰水杨酸(阿司匹林,ASA)与来自西伯利亚落叶松和兴安落叶松的阿拉伯半乳聚糖(AG)的包合物。在本研究中,我们研究了合成的包合物在固态和水溶液中的物理化学性质以及它们的抗聚集和致溃疡活性。通过核磁共振(NMR)弛豫技术获得了包合物形成的证据。结果表明,在水溶液中,SA和ASA分子在与AG大分子形成的复合物和溶液之间快速交换。计算了阿司匹林复合物的稳定常数。结果表明,与通过混合各组分溶液得到的复合物相比,机械化学合成的复合物更稳定。ASA包合物的抗血小板作用提高了两倍。这使得抗血栓药物的剂量及其致溃疡活性得以降低。这些结果证实了基于ASA设计具有更高活性和安全性的新制剂的可能性。