Du Qiu, Du Shou-Ying, Li Peng-Yue, Lu Yang, Bai Jie, Teng Hui-Hui, Wang Zhen, Zhang Qing
School of Chinese Pharmacy, Beijing University of Traditional Chinese Medicine, Beijing 100102, China.
Zhongguo Zhong Yao Za Zhi. 2016 Jan;41(2):303-308. doi: 10.4268/cjcmm20160222.
This experiment focused on the effect of salvianolic acid B's nasal absorption characteristics in rats. In the study, HPLC determination of salvianolic acid B(SalB) in perfusion liquid was established to examine the SalB nasal irritation in different pH buffers and stability in nasal perfusion solution, and systematically study in vivo nasal absorption characteristics of SalB. Improved rats were adopted to establish the in situ nasal perfusion model to measure the release of total protein and lactate dehydrogenase in perfusion fluid, quantitatively evaluate the nasal irritation and the stability in perfusion liquid of pH 4.0, 5.0, 6.0 SalB phosphate buffer, compare the absorption of SalB in pH 5.0 buffer solution with low, medium and high concentrations (200, 400, 800 mg•L⁻¹). According to the results, nasal irritation: pH 4.0>pH 5.0>pH 6.0, RSD of pH 6.0 SalB buffer solution within 24 h was 3.1%, stability was poor. PH 5.0 SalB buffer solution had a smaller irritation and good stability. According to the nose perfusion test in rats, the nasal absorption of SalB fitted the first-order process and could be considered as passive absorption based on concentration gradient. SalB buffer solution of pH 5.0 had also a small nasal irritation and good stability, with a good absorption in rat nasal perfusion test, which therefore had a certain significance for the development of SalB nasal formulation.
本实验着重研究了丹酚酸B在大鼠体内的鼻腔吸收特性。实验中,建立了高效液相色谱法测定灌注液中丹酚酸B(SalB)的含量,以考察其在不同pH缓冲液中的鼻腔刺激性及在鼻腔灌注液中的稳定性,并系统研究了SalB的体内鼻腔吸收特性。采用改良大鼠建立原位鼻腔灌注模型,测定灌注液中总蛋白和乳酸脱氢酶的释放量,定量评价pH 4.0、5.0、6.0的SalB磷酸盐缓冲液的鼻腔刺激性及在灌注液中的稳定性,比较低、中、高浓度(200、400、800 mg•L⁻¹)的SalB在pH 5.0缓冲溶液中的吸收情况。结果显示,鼻腔刺激性:pH 4.0>pH 5.0>pH 6.0,pH 6.0的SalB缓冲溶液在24 h内的相对标准偏差为3.1%,稳定性较差。pH 5.0的SalB缓冲溶液刺激性较小且稳定性良好。根据大鼠鼻腔灌注试验,SalB的鼻腔吸收符合一级过程,基于浓度梯度可视为被动吸收。pH 5.0的SalB缓冲溶液鼻腔刺激性小且稳定性良好,在大鼠鼻腔灌注试验中吸收良好,因此对SalB鼻腔制剂的开发具有一定意义。