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盐酸聚六亚甲基胍的抗菌及伤口愈合潜力评估及其毒性作用。

Evaluation of the antiseptic and wound healing potential of polyhexamethylene guanidine hydrochloride as well as its toxic effects.

作者信息

Dias Fernanda Gosuen Gonçalves, Pereira Lucas de Freitas, Parreira Renato Luis Tame, Veneziani Rodrigo Cassio Sola, Bianchi Thamires Chiquini, Fontes Vitória Ferreira Nogueira de Paula, Galvani Marina de Carlos, Cerce Danielle Dal Picolo, Martins Carlos Henrique Gomes, Rinaldi-Neto Francisco, Ferreira Natália Helen, da Silva Lucas Henrique Domingos, de Oliveira Lucas Teixeira Souza, Esperandim Tábata Rodrigues, de Sousa Francielle Aparecida, Ambrósio Sérgio Ricardo, Tavares Denise Crispim

机构信息

Universidade de Franca, Avenida Dr. Armando Salles de Oliveira, 201 - Parque Universitário, 14404-600, Franca, São Paulo, Brazil.

Universidade de Franca, Avenida Dr. Armando Salles de Oliveira, 201 - Parque Universitário, 14404-600, Franca, São Paulo, Brazil.

出版信息

Eur J Pharm Sci. 2021 May 1;160:105739. doi: 10.1016/j.ejps.2021.105739. Epub 2021 Jan 30.

Abstract

The synthetic polyhexamethylene guanidine hydrochloride (PHMGH) polymer presents antifungal and antimicrobial activities in vitro. However, in vivo reports regarding its antiseptic and healing activity are scarce in the scientific literature. Thus, the present study aimed to evaluate the antimicrobial and healing effects, as well as toxicological parameters, of a topical solution containing 0.5% PHMGH (Akwaton®) in the treatment of superficial skin wounds experimentally induced on the dorsum of rodents. In addition, non-clinical safety studies were also conducted for use in human health, such as acute oral toxicity and genotoxicity tests. Animals did clinically not present dermatitis. After two days of topical treatment, PHMGH showed a significant antiseptic effect compared to the untreated group, reducing the number of colony-forming units by 72%, reaching 100% on the fourth day of treatment. The animals treated with PHMGH showed a significant area reduction of the skin lesions in relation to the untreated group, indicating a healing effect of the polymer. Moreover, PHMGH treatment led to a significant increase in fibroblasts when compared to the untreated group, revealing its healing action. No significant differences were observed between the biochemical indicators of hepatoxicity and nephrotoxicity, nor genotoxicity between the PHMGH-treated and the negative control groups. The results of acute oral toxicity showed that PHMGH at 5% presents a lethal dose 50% greater than the 2000 mg/kg. At a concentration of 5%, PHMGH did not show genotoxicity nor cytotoxicity at doses up to 1500 mg/kg through the micronucleus assay in mice. Therefore, 0.5% PHMGH showed an antimicrobial and healing effect, with no toxicity, and could be a promising adjunct in the microbial control of healing wounds.

摘要

合成聚六亚甲基胍盐酸盐(PHMGH)聚合物在体外具有抗真菌和抗菌活性。然而,科学文献中关于其防腐和愈合活性的体内报告却很少。因此,本研究旨在评估含0.5%PHMGH(Akwaton®)的局部溶液对啮齿动物背部实验性诱导的浅表皮肤伤口的抗菌和愈合效果以及毒理学参数。此外,还进行了用于人类健康的非临床安全性研究,如急性口服毒性和遗传毒性试验。动物临床上未出现皮炎。局部治疗两天后,与未治疗组相比,PHMGH显示出显著的防腐效果,使菌落形成单位数量减少72%,在治疗第四天达到100%。与未治疗组相比,用PHMGH治疗的动物皮肤损伤面积显著减小,表明该聚合物具有愈合作用。此外,与未治疗组相比,PHMGH治疗导致成纤维细胞显著增加,揭示了其愈合作用。在肝毒性和肾毒性的生化指标之间,以及PHMGH治疗组和阴性对照组之间的遗传毒性方面,未观察到显著差异。急性口服毒性结果表明,5%的PHMGH的半数致死剂量大于2000mg/kg。在5%的浓度下,通过小鼠微核试验,PHMGH在高达1500mg/kg的剂量下未显示遗传毒性和细胞毒性。因此,0.5%的PHMGH显示出抗菌和愈合作用,且无毒性,可能是愈合伤口微生物控制中有前景的辅助药物。

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