Biopharmaceutical aspects of techno­logy of wound­healing gels containing silver(I) complex with 2-­(4,6-­di-­tert-­butyl-­2,3-­dihydroxyphenylsulphanyl)acetic acid

H. Harbatsevich, Sergei I. Stakhevich, N. Loginova, G. Ksendzova, N. Osipovich, I. N. Slabko, V. V. Butkevich, Zhanna A. Makarevich, Lyudmila V. But'ko
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Abstract

The object of the work is to develop optimal composition of a gel with wound­healing ability based on Ag(I) complex with 2­(4,6­di­tert­butyl­2,3­dihydroxyphenylsulphanyl)acetic acid to produce a novel effective remedy. It was found that propylene glycol (PG) favours the formation of more fine suspension of Ag(I) complex, and introduction of polyvinylpyrrolidone (PVP) hinders aggregation of the particles of the complex, thus providing optimal dispersity of the gel suspension. The gels based on methyl cellulose (MC) are characterized by an acceptable degree of release of Ag(I) complex. It is the gels containing PG and PVP that are characterized by the most complete release of the active substance, which is in agreement with the data on the optimal dispersity. It was found that PG and PVP being introduced into the gel composition increase the osmotic activity of the gel considerably. The optimal composition of the ointment base was determined, %: MC – 3.5; PVP – 5.0; 0.1 mol/L citric acid solution – 5.0; PG – 20.0; water for injections – up to 100.0. The gel obtained was shown to surpass «Dermazin» cream and «Levomecol» ointment in wound­healing ability, while the content of the active substance was significantly lower (0.5 %), and to promote wounds to be cleansed of microorganisms fast and completely too. No accumulation of silver in the liver was found when the gel was used medicinally.
含银(I)与2—(4,6—二叔—丁基—2,3—二羟基苯基磺胺基)乙酸配合物的伤口愈合凝胶的生物制药技术
这项工作的目的是开发一种基于银(I)与2 -(4,6 -二叔丁基- 2,3 -二羟基苯基磺胺基)乙酸配合物的具有伤口愈合能力的凝胶的最佳组合,以产生一种新的有效药物。发现丙二醇(PG)有利于银(I)配合物形成更细的悬浮液,而聚乙烯吡咯烷酮(PVP)的引入阻碍了配合物颗粒的聚集,从而提供了最佳的凝胶悬浮液分散性。基于甲基纤维素(MC)的凝胶具有可接受的Ag(I)配合物释放度。含有PG和PVP的凝胶的活性物质释放最完全,这与最佳分散性的数据一致。结果表明,在凝胶组分中加入PG和PVP可显著提高凝胶的渗透活性。确定软膏基质的最佳组成:%:MC - 3.5;PVP - 5.0;0.1 mol/L柠檬酸溶液- 5.0;Pg - 20.0;注射用水-高达100.0。所获得的凝胶在伤口愈合能力上超过了“Dermazin”霜和“左旋美可”软膏,而活性物质的含量明显低于“Dermazin”霜和“左旋美可”软膏(0.5%),并且也能促进伤口微生物的快速彻底清洁。当凝胶作为药物使用时,没有发现银在肝脏中积聚。
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