1.Efficacy and safety of Liqingtong granules in the treatment of hyperuricemia: A randomized double-blind placebo-controlled pilot clinical trial
Jinlian Liu ; Yi Yang ; Meiyu Lv ; Wenting Fei ; Songrui Di ; Mei Luo ; Qing Lin ; Chun Wang ; Linyuan Wang ; Jianjun Zhang
Journal of Traditional Chinese Medical Sciences 2024;11(4):415-422
Objective:
To investigate the efficacy and safety of Liqingtong (LQT) granules in patients with dampness-heat hyperuricemia.
Methods:
A randomized, double-blind, placebo-controlled pilot trial was conducted at the 983rd Hospital of the Joint Logistic Support Force of the People's Liberation Army from March 15, 2023, to August 10, 2023. In total, 119 participants were enrolled in this trial, and participants were given either LQT granules or placebo for 60 days based on a health education. The primary outcome was serum uric acid (SUA) level, and the secondary outcome was the traditional Chinese medicine (TCM) symptom score, measured on days 0, 30, and 60. Safety indicators, including liver function, kidney function, blood routine, glucose, blood lipid, blood pressure, and heart rate were tested on days 0 and 60 of the trial. The data were analyzed using Prism 9 software, and the significance level was set at P < .05.
Results:
Among 119 participants, six in the LQT granule group and seven in the placebo group dropped out, and 106 participants completed clinical observation. Baseline information, including SUA levels, TCM symptom scores, and other clinical characteristics, did not differ between the groups. At the end of the trial, compared with baseline values, the SUA levels in the LQT granule group decreased (P < .001), and no significant change was observed in the placebo group (P = .422); compared with the placebo group, the SUA levels decreased in the LQT granule group (P = .001). Compared with baseline values, the total TCM symptom scores in the LQT granule group decreased (P < .001), with no change in the placebo group (P = .136). Safety indicators did not differ significantly between the two groups.
Conclusion
The pilot trial demonstrated the potential of LQT granules to lower SUA levels and improve symptoms of dampness and heat.
2.Pharmacokinetics,distribution,and excretion of sodium oligomannate,a recently approved anti-Alzheimer's disease drug in China
Jiaojiao LU ; Qiongqun PAN ; Jieqiang ZHOU ; Yan WENG ; Kaili CHEN ; Lv SHI ; Guanxiu ZHU ; Chunlin CHEN ; Liang LI ; Meiyu GENG ; Zhenqing ZHANG
Journal of Pharmaceutical Analysis 2022;12(1):145-155
The National Medical Products Administration has authorized sodium oligomannate for treating mild-to-moderate Alzheimer's disease.In this study,an LC-MS/MS method was developed and validated to quantitate sodium oligomannate in different biomatrices.The plasma pharmacokinetics,tissue distri-bution,and excretion of sodium oligomannate in Sprague-Dawley rats and beagle dogs were system-atically investigated.Despite its complicated structural composition,the absorption,distribution,metabolism,and excretion profiles of the oligosaccharides in sodium oligomannate of different sizes and terminal derivatives were indiscriminate.Sodium oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport following oral administration,with very low oral bioavail-ability in rats(0.6%-1.6%)and dogs(4.5%-9.3%).Absorbed sodium oligomannate mainly resided in circulating body fluids in free form with minimal distribution into erythrocytes and major tissues.So-dium oligomannate could penetrate the blood-cerebrospinal fluid(CSF)barrier of rats,showing a con-stant area under the concentration-time curve ratio(CSF/plasma)of approximately 5%.The cumulative urinary excretion of sodium oligomannate was commensurate with its oral bioavailability,supporting that excretion was predominantly renal,whereas no obvious biliary secretion was observed following a single oral dose to bile duct-cannulated rats.Moreover,only 33.7%(male)and 26.3%(female)of the oral dose were recovered in the rat excreta within 96 h following a single oral administration,suggesting that the intestinal flora may have ingested a portion of unabsorbed sodium oligomannate as a nutrient.
3.Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma.
Yingqiang LIU ; Zhengsheng ZHAN ; Zhuang KANG ; Mengyuan LI ; Yongcong LV ; Shenglan LI ; Linjiang TONG ; Fang FENG ; Yan LI ; Mengge ZHANG ; Yaping XUE ; Yi CHEN ; Tao ZHANG ; Peiran SONG ; Yi SU ; Yanyan SHEN ; Yiming SUN ; Xinying YANG ; Yi CHEN ; Shanyan YAO ; Hanyu YANG ; Caixia WANG ; Meiyu GENG ; Wenbin LI ; Wenhu DUAN ; Hua XIE ; Jian DING
Acta Pharmaceutica Sinica B 2023;13(12):4748-4764
Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).