Pharmacokinetics of five phthalides in volatile oil of Ligusticum sinense Oliv.cv. Chaxiong, and comparison study on physicochemistry and pharmacokinetics after being formulated into solid dispersion and inclusion compound
| Autor: | Zhang Guosong, Jian-fang Feng, Zhang Wenliu, Dong-xun Li, Lei Zhiqiang, Ying-huai Zhong, Xue-mei Liu, Ping Deng, Hu Pengyi |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Solid dispersion Administration Oral 030226 pharmacology & pharmacy Inclusion compound Phthalide Rats Sprague-Dawley Other systems of medicine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Oral administration Animals Plant Oils Ligusticum Infusions Intravenous Dissolution Chaxiong Benzofurans Chromatography Molecular Structure Rats Bioavailability Solvent Complementary and alternative medicine chemistry Phthalides Physicochemical characterization Dispersion (chemistry) RZ201-999 Rhizome 030217 neurology & neurosurgery Research Article Phytotherapy |
| Zdroj: | BMC Complementary Medicine and Therapies BMC Complementary Medicine and Therapies, Vol 21, Iss 1, Pp 1-16 (2021) |
| ISSN: | 2662-7671 |
| DOI: | 10.1186/s12906-021-03289-z |
| Popis: | Backgrounds The dried rhizome of Ligusticum sinense Oliv.cv. Chaxiong has been used to treat cardiovascular and cerebrovascular diseases, atherosclerosis, anemia and stroke. A high purity extract from chaxiong (VOC, brownish yellow oil) was extracted and separated. Its main components were senkyunolide A (SA, 33.81%), N-butylphthalide (NBP, 1.38%), Neocnidilide (NOL, 16.53%), Z-ligustilide (ZL, 38.36%), and butenyl phthalide (BP, 2.48%), respectively. Little is known about the pharmacokinetics of these phthalides in Chaxiong, and different preparations to improve the physicochemistry and pharmacokinetics of VOC have not been investigated. Methods At different predetermined time points after oral administration or intravenous administration, the concentrations of SA, NBP, NOL, ZL and BP in the rat plasma were determined using LC-MS/MS, and the main PK parameters were investigated. VOC-P188 solid dispersion and VOC-β-CD inclusion compound were prepared by melting solvent method and grinding method, respectively. Moreover, the physicochemical properties, dissolution and pharmacokinetics of VOC-P188 solid dispersion and VOC-β-CD inclusion compound in rats were assessed in comparison to VOC. Results The absorptions of SA, NBP, NOL, ZL and BP in VOC were rapid after oral administration, and the absolute bioavailability was less than 25%. After the two preparations were prepared, dissolution rate was improved at pH 5.8 phosphate buffer solution. Comparing VOC and physical mixture with the solid dispersion and inclusion compound, it was observed differences occurred in the chemical composition, thermal stability, and morphology. Both VOC-P188 solid dispersion and VOC-β-CD inclusion compound had a significantly higher AUC and longer MRT in comparison with VOC. Conclusion SA, NBP, NOL, ZL and BP in VOC from chaxiong possessed poor absolute oral bioavailability. Both VOC-P188 solid dispersion and VOC-β-CD inclusion compound could be prospective means for improving oral bioavailability of SA, NBP, NOL, ZL and BP in VOC. |
| Databáze: | OpenAIRE |
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