Ramot Yuval, Hazan Zadik, Lucassen Andre, Adamsky Konstantin, Ross Vanessa, Young Nigel, Saunders Matt, Ehall Helmut, Nyska Abraham
1 Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
2 Regenera Pharma, Nes-Ziona, Israel.
Toxicol Pathol. 2018 Aug;46(6):693-705. doi: 10.1177/0192623318786428. Epub 2018 Jul 15.
Mastic gum extracts are widely used as herbal remedies and are being tested for several clinical indications. Nevertheless, information on their safety is limited. RPh201 is an extract of the mastic gum, formulated and stabilized in a proprietary method, which is being developed as a novel drug candidate for neurological indications. The aim of this study was to assess the systemic toxic potential of RPh201, administered twice weekly by subcutaneous injections to minipigs, after 39 weeks of administration followed by a recovery period of 6 weeks. No clinical or dose-related signs were observed, but treatment-related findings were seen at the injection sites of the high-dose animals, composed of abscesses, chronic inflammation, and subcutaneous fibrosis. Abscesses >30 mm in size, graded as marked severity, were confined to the high-dose group and were considered as adverse. Minimal-slight subcutaneous and lymph nodes abscesses seen in control, low, and intermediate doses, related to the vehicle (cottonseed oil), were not considered as adverse. Additionally, minimal-to-slight cystic spaces or vacuolation related to the vehicle were observed in the skin, lymph nodes, kidney, and lungs. These findings were considered not to be adverse. The no-observed-adverse-effect level was considered to be 12.5 mg/kg/occasion.
乳香提取物被广泛用作草药疗法，并且正在针对多种临床适应症进行测试。然而，关于其安全性的信息有限。RPh201是一种乳香提取物，采用专利方法配制并稳定化，正被开发为一种用于神经学适应症的新型候选药物。本研究的目的是评估RPh201的全身毒性潜力，每周两次皮下注射给小型猪，给药39周后再进行6周的恢复期。未观察到临床或剂量相关体征，但在高剂量动物的注射部位发现了与治疗相关的结果，包括脓肿、慢性炎症和皮下纤维化。大小>30 mm的脓肿，严重程度分级为重度，仅限于高剂量组，被视为不良反应。在对照、低剂量和中剂量组中观察到的与赋形剂（棉籽油）相关的最小-轻度皮下和淋巴结脓肿，不被视为不良反应。此外，在皮肤、淋巴结、肾脏和肺部观察到与赋形剂相关的最小-轻度囊性间隙或空泡化。这些发现被认为不是不良反应。未观察到不良反应的水平被认为是12.5 mg/kg/次。
