Journal of Natural Medicines ( IF 2.5 ) Pub Date : 2022-08-24 , DOI: 10.1007/s11418-022-01645-y Takashi Ogihara 1, 2 , Masato Kagawa 1, 2 , Rintarou Yamanaka 1, 2 , Satoshi Imai 1 , Kotaro Itohara 1 , Daiki Hira 1 , Shunsaku Nakagawa 1 , Atsushi Yonezawa 1, 2 , Michiho Ito 3 , Takayuki Nakagawa 1 , Tomohiro Terada 1 , Kazuo Matsubara 1, 4
|
Chemotherapy-induced oral mucositis (COM) is a common adverse effect of cancer chemotherapy. Several clinical studies reported that repetitive use of mouthwashes containing 2.5–6.25% Hangeshashinto (HST), a Kampo formula, relieves COM, but the effect is insufficient. To solve this problem, we produced an oral ointment of 12% HST extract (considered quantitatively equivalent to 20% commercially available HST), which will increase the local concentrations of its active ingredients and prolong the contact time with COM. In this study, we evaluated the pharmaceutical properties (spreadability and stability) of HST oral ointment. In addition, its safety (oral mucosal irritation) and therapeutic effects on 5-fluorouracil-induced oral mucositis were evaluated in male Syrian hamsters. The HST ointment showed good spreadability and stability for more than 8 weeks at 4 °C. In the oral mucosal irritation test, topical application of HST ointment (0.2 g) three times per day for 14 days had no adverse effect on the oral mucosa of hamsters. In hamsters treated with 5-fluorouracil (60 mg/kg) twice, COM was induced by a submucosal injection of 5% acetic acid into the cheek pouch. When HST ointment (50 µg) was topically applied to the mucositis area once per day for 12 days, the area and macroscopic score of mucositis were significantly decreased, and the depth of the wound tended to be reduced compared with the lactose ointment-treated control animals. These findings suggest that HST oral ointment shows good properties in spreadability, stability, and safety, and elicits a therapeutic effect in an animal model of COM.
Graphical abstract
中文翻译：
Hangeshashinto口服软膏的制备、药学性质及其对5-氟尿嘧啶所致叙利亚仓鼠口腔粘膜炎的安全性和有效性
化疗引起的口腔粘膜炎（COM）是癌症化疗的常见不良反应。多项临床研究表明，重复使用含有 2.5-6.25% Hangeshashinto (HST)（一种汉方配方）的漱口水可以缓解 COM，但效果不够。为了解决这个问题，我们生产了12％HST提取物的口服软膏（在数量上相当于20％市售HST），这将增加其活性成分的局部浓度并延长与COM的接触时间。在本研究中，我们评估了 HST 口服软膏的药物特性（铺展性和稳定性）。此外，还在雄性叙利亚仓鼠中评估了其安全性（口腔粘膜刺激）和对 5-氟尿嘧啶引起的口腔粘膜炎的治疗效果。 HST软膏在4°C下显示出良好的铺展性和稳定性超过8周。口腔粘膜刺激试验中，局部涂抹HST软膏（0.2克），每日3次，连续14天，对仓鼠口腔粘膜无不良影响。在用 5-氟尿嘧啶 (60 mg/kg) 处理两次的仓鼠中，通过向颊囊粘膜下注射 5% 乙酸来诱导 COM。当将HST软膏（50μg）局部涂抹于粘膜炎区域，每天一次，持续12天时，与乳糖软膏处理的对照相比，粘膜炎的面积和肉眼评分显着减少，伤口深度趋于减少。动物。这些研究结果表明，HST 口服软膏在涂抹性、稳定性和安全性方面表现出良好的特性，并在 COM 动物模型中产生了治疗效果。
京公网安备 11010802027423号