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含有桧木醇和 4-异丙基-3-甲基苯酚的口腔护理凝胶对口腔内病原微生物的抗菌作用。

Antimicrobial effect of oral care gel containing hinokitiol and 4-isopropyl-3-methylphenol against intraoral pathogenic microorganisms.

机构信息

Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Ohu University, Koriyama, Japan.

Department of Pharmacy, Ohu University Hospital, Koriyama, Japan.

出版信息

PLoS One. 2023 Sep 1;18(9):e0283295. doi: 10.1371/journal.pone.0283295. eCollection 2023.

Abstract

OBJECTIVE

Deterioration of oral hygiene is closely related to an increase in severity and mortality of corona virus disease-19 (COVID-19), and also contributes to the development of various diseases such as aspiration pneumonia or Alzheimer's. Oral care is attracting high interest in Japan, which has entered a super-aging society. In this study, we aimed to investigate whether commercially available Hinora® (HO), an oral care gel containing hinokitiol and 4-isopropyl-3-methylphenol (IPMP), has biofilm formation inhibitory and antimicrobial activities against various intraoral pathogen microorganisms.

METHOD

Candida species, Aggregatibacter actinomycetemcomitans, Staphylococcus aureus, and Pseudomonas aeruginosa were selected during the study period, all of which were analyzed using antimicrobial disc, microorganism turbidity, and crystal violet assays. In addition, the germ tube test using Candida albicans (C. albicans) was performed with a modification of Mackenzie's method. Images for morphological observation of the germ tubes were acquired using an inverted microscope. For comparison between products, we used Refrecare® (RC), which only contains hinokitiol (not containing IPMP).

RESULTS

All the intraoral pathogenic microorganisms showed drug susceptibility against undiluted forms of HO and/or RC. In particular, HO was more effective at lower concentrations than RC. In the HO-added group, inhibition circles were observed in all bacteria except P. aeruginosa when added at a concentration of 0.5 g/mL or more. The optical density values at 590 nm (crystal violet) and/or 600 nm (microorganism turbidity) of all the fungi and bacteria were significantly lower when cultured in medium with HO. Inhibition of growth or biofilm formation was observed when HO was added at a concentration of 0.05 g/mL or higher. To investigate the action mechanism of HO, germ tube tests were performed in C. albicans. The results showed that culturing C. albicans in soybean-casein digest broth with HO (0.05 g/mL) significantly suppressed germ tube formation.

CONCLUSIONS

These data suggest that oral care gel-containing hinokitiol and IPMP has strong biofilm formation inhibitory activity, as well as antifungal and antimicrobial effects against Candida fungi and multiple intraoral pathogenic microorganisms. Therefore, it may be a promising treatment option for oral infections.

摘要

目的

口腔卫生恶化与 2019 年冠状病毒病(COVID-19)严重程度和死亡率的增加密切相关,并且还会导致吸入性肺炎或阿尔茨海默病等各种疾病的发生。口腔护理在已经进入超老龄化社会的日本备受关注。在这项研究中,我们旨在研究市售 Hinora®(HO)——一种含有桧木醇和 4-异丙基-3-甲基苯酚(IPMP)的口腔护理凝胶——是否对各种口腔病原体微生物具有抑制生物膜形成和抗菌活性。

方法

在研究期间选择了白色念珠菌、伴放线放线杆菌、金黄色葡萄球菌和铜绿假单胞菌作为分析对象,所有分析均采用抗菌圆盘、微生物浊度和结晶紫测定法进行。此外,还使用 Mackenzie 方法的改良版对白念珠菌(C. albicans)进行了芽管试验。使用倒置显微镜获取芽管形态观察图像。为了进行产品比较,我们使用了仅含有桧木醇(不含 IPMP)的 Refrecare®(RC)。

结果

所有口腔病原体微生物对 HO 和/或 RC 的未稀释形式均表现出药物敏感性。特别是,HO 在较低浓度下比 RC 更有效。在添加 HO 的浓度为 0.5g/mL 或更高时,除铜绿假单胞菌外,所有细菌均观察到抑菌环。当在含有 HO 的培养基中培养时,所有真菌和细菌的 590nm(结晶紫)和/或 600nm(微生物浊度)吸光度值显著降低。当添加浓度为 0.05g/mL 或更高时,观察到生长或生物膜形成的抑制。为了研究 HO 的作用机制,在白色念珠菌中进行了芽管试验。结果表明,在含有 HO(0.05g/mL)的大豆酪蛋白消化肉汤中培养白色念珠菌时,芽管形成显著受到抑制。

结论

这些数据表明,含有桧木醇和 IPMP 的口腔护理凝胶具有很强的抑制生物膜形成的活性,以及对白色念珠菌真菌和多种口腔病原体微生物的抗真菌和抗菌作用。因此,它可能是一种有前途的口腔感染治疗选择。

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