Preparation and pharmaceutical properties of Hangeshashinto oral ointment and its safety and efficacy in Syrian hamsters with 5-fluorouracil-induced oral mucositis

Takashi Ogihara, Masato Kagawa, Rintarou Yamanaka, Satoshi Imai, Kotaro Itohara, Daiki Hira, Shunsaku Nakagawa, Atsushi Yonezawa, Michiho Ito, Takayuki Nakagawa, Tomohiro Terada, Kazuo Matsubara

Research output: Contribution to journalArticlepeer-review

Abstract

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: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)53-63
Number of pages11
JournalJournal of Natural Medicines
Volume77
Issue number1
DOIs
Publication statusPublished - 2023 Jan
Externally publishedYes

Keywords

  • 5-fluorouracil
  • Chemotherapy-induced oral mucositis
  • Hamster
  • Hangeshashinto
  • Oral ointment

ASJC Scopus subject areas

  • Drug Discovery
  • Complementary and alternative medicine
  • Pharmaceutical Science
  • Organic Chemistry

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