基于n -亚肯咪唑锌配合物衍生物的有效伤口愈合剂:未来前景和机遇

Q3 Pharmacology, Toxicology and Pharmaceutics
Svetlana A. Lebedeva, Pavel A. Galenko-Yaroshevsky (Jr.), Tatiana V. Fateeva, Sergey S. Pashin, Nataliya R. Pashina, Irina B. Nektarevskaya, Andrey V. Zadorozhniy, Olga V. Shelemekh, Marina Yu. Ravaeva, Elena N. Chuyan, Lusine O. Alukhanyan, Tereza R. Glechyan, Kerim Mutig, Maria Yu. Materenchuk
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These drugs can easily penetrate into damaged tissues and stimulate metabolic processes. Zinc complexes with imidazole derivatives are of a particular interest. Imidazole acts as a structural fragment of many natural physiologically active compounds, thus providing targeted delivery of this essential trace element into the wound for inclusion in the multicascade mechanism of wound healing. The aim of the study: to provide experimental evidence for effects of recently developed zinc complexes with N-alkenylimidazole as wound healing agents. Materials and Methods: Wound-healing effects of six 1% gels containing distinct N-alkenylimidazole zinc complexe derivatives based on the Na-carboxymethylcellulose (Na-CMC) were comparatively studied in 128 outbred white rats of both genders. The Na-CMC-based Zinc Sulfate 1% gel, Methyluracil and Solcoseryl served as reference drugs. 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引用次数: 0

摘要

导读:国内外市售药物治疗各种皮肤损伤的疗效远非理想。这些药物没有普遍作用,但会引起明显的副作用。开发具有抗菌特性的创新伤口愈合药物的需求非常明显,这些药物可以增加皮肤的天然保护功能。含锌纳米颗粒的药物化合物越来越被认为是一个有前景的治疗方向。这些药物很容易渗透到受损组织中,刺激代谢过程。锌配合物与咪唑衍生物是特别感兴趣的。咪唑作为许多天然生理活性化合物的结构片段,从而提供了这种必需的微量元素靶向递送到伤口中,用于伤口愈合的多级联机制。本研究的目的是:为最近开发的锌配合物与n -亚肯咪唑作为伤口愈合剂的作用提供实验证据。材料与方法:以na -羧甲基纤维素(Na-CMC)为基础,比较研究了6种含有不同N-alkenylimidazole锌络合物衍生物的1%凝胶对128只雌雄远交种大鼠的创面愈合效果。以na - cmc为基础的1%硫酸锌凝胶、甲基尿嘧啶和索克瑟利为对照药物。在进行锌配合物的局部耐受性研究后,对麻醉动物造成同等大小的线性和平面无菌伤口。在治疗开始后第8天和第28天,通过伤口大小和炎症反应、上皮、肉芽组织、血管生成和坏死的组织学检查来评估愈合程度。使用激光多普勒血流仪(LDF)评估皮肤微循环系统,在腹腔注射试验化合物30和60分钟后记录血流指标。采用双串联稀释法测定锌类化合物对细菌和真菌的最低抑菌浓度,并进行体外抑菌活性测定。统计数据处理采用Statistica 12软件包。结果与讨论:在线性伤口模型中,6种锌化合物处理的所有动物在第8天伤口大小几乎完全减少(92% -100%,p<0.05),显著超过对照动物的伤口愈合(减少67- 88%,p<0.05)和参考药物的效果(减少83-86%,p<0.05)。在平面创面模型中,使用含有n -异丙烯咪唑双乙酸锌(编码为Pilim-1)的凝胶创面愈合效果最显著。相应的组织学检查显示完全上皮化的迹象,表皮没有破坏性变化,皮肤附属物恢复,存在成熟的肉芽组织。通过对灌注的显著影响和LDF-gram孤立节律的振幅来判断,20 mg/kg剂量的Pilim-1腹腔注射改善了大鼠皮肤的微循环。此外,Pilim-1具有中等抑菌和抑菌活性,其抑菌活性是甲硝唑的2倍。结论:1% n -亚肯咪唑锌络合衍生物凝胶外用与现有对照药物相比,可促进未感染的直线和平面创面愈合。Pilim-1锌化合物的治疗效果最为显著。Pilim-1的体外抗菌作用对其治疗感染皮肤伤口的潜在意义有进一步的研究意义。这种物质的再生作用为开发具有改善伤口愈合性能的新药开辟了前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effective wound healing agents based on N-alkenylimidazole zinc complexes derivatives: future prospects and opportunities
Introduction: The therapeutic effect of commercially available domestic and foreign drugs for the treatment of various skin injuries is far from optimal. These drugs have no universal effects, but cause pronounced side reactions. There is a clear demand for development of innovative wound-healing drugs with antimicrobial properties, which increase the natural protective function of the skin. Pharmaceutical compounds with zinc nanoparticles have been increasingly recognized as a promising therapeutic direction. These drugs can easily penetrate into damaged tissues and stimulate metabolic processes. Zinc complexes with imidazole derivatives are of a particular interest. Imidazole acts as a structural fragment of many natural physiologically active compounds, thus providing targeted delivery of this essential trace element into the wound for inclusion in the multicascade mechanism of wound healing. The aim of the study: to provide experimental evidence for effects of recently developed zinc complexes with N-alkenylimidazole as wound healing agents. Materials and Methods: Wound-healing effects of six 1% gels containing distinct N-alkenylimidazole zinc complexe derivatives based on the Na-carboxymethylcellulose (Na-CMC) were comparatively studied in 128 outbred white rats of both genders. The Na-CMC-based Zinc Sulfate 1% gel, Methyluracil and Solcoseryl served as reference drugs. After performing the local tolerance study of zinc complexes, linear and planar sterile wounds of comparable size were inflicted in anesthetized animals. The degree of healing was evaluated on the day 8 and day 28 after the treatment start by wound sizes and histological examination of inflammatory response, epithelization, granulation tissue, angiogenesis, and necrosis. The skin microcirculation system was evaluated using the laser Doppler Flowmetry (LDF), whereby the blood flow indicators were recorded 30 and 60 minutes after intraperitoneal administration of the trial compound. The antimicrobial activity of the zinc compounds was determined in vitro by means of their minimum inhibitory concentration suppressing the bacteria and fungi growth using the double serial dilution method in liquid culture media. The statistical data processing was performed using the Statistica 12 software package. Results and Discussion: In the linear wound model, all animals treated with either of six experimental zinc compounds showed almost complete reduction in wound size (92-100%, p<0.05) on the day 8, significantly exceeding the wound healing in the control animals (reduction by 67-88 %, p<0.05) and effects of the reference drugs (reduction by 83-86%, p<0.05). In the planar wound model, the most significant wound healing effect was reached by using the gel containing N-isopropenylimidazole zinc diacetate (encoded as Pilim-1). The respective histological examination showed signs of complete epithelialization, absence of destructive changes in the epidermis, restoration of skin appendages and presence of mature granulation tissue. Intraperitoneal Pilim-1 administration at a dose of 20 mg/kg improved microcirculation in the rat skin, as judged by significant effects on perfusion and the amplitudes of the isolated rhythms of the LDF-gram. In addition, Pilim-1 exerted a moderate bacteriostatic and fungistatic activity, which was 2 times greater than the antimicrobial activity of Metronidazole. Conclusion: Topical application of gels containing 1% N-alkenylimidazole zinc complex derivatives accelerates the healing of uninfected linear and planar wounds in comparison with the established reference drugs. The Pilim-1 zinc compound exhibited the most pronounced therapeutic effect. The observed in vitro antimicrobial action of Pilim-1 is of further interest for potential implications in treatment of infected skin wounds. The regenerative effect of this substance opens prospects for development of new drugs with improved wound healing properties.
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来源期刊
Research Results in Pharmacology
Research Results in Pharmacology Medicine-Pharmacology (medical)
CiteScore
1.50
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32
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12 weeks
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