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BACKGROUND: Traditional Chinese medicine formulations often contain hydrophobic components with limited solubility and stability, leading to low oral bioavailability. Self-assembled nanoparticles (SANs) have shown promise in enhancing oral bioavailability of these components. However, whether un-decocted Chinese herbal pellets can generate SANs and the impact of SANs formed by multiple components on pharmacokinetic parameters remains unexplored. METHODS: In this study, single-factor approach was employed to determine the optimal separation method of nano-emulsion phase of XiaoYao pill (N-XY). Morphological and particle size analyses confirmed the nanoscale nature of N-XY. High-performance liquid chromatography (HPLC) fingerprint analysis was conducted to compare the distribution of active ingredients among three different phases of XiaoYao pill (XY pill). In vitro release studies were performed to evaluate the release mechanism of four ingredients from N-XY. Additionally, in vivo pharmacokinetics and tissue distribution behaviors were investigated in rats. RESULTS: N-XY exhibited uniform and stable characteristics as a water-in-oil (O/W) nano-emulsion. Fingerprint analysis identified 25 characteristic peaks and 8 key ingredients in N-XY, with the highest peak areas. In vitro release studies showed a sustained release behavior of N-XY. The pharmacokinetics study showed that the ferulic acid of N-XY had a 1.37-fold higher AUC, 1.44-fold lower Vd/F, 1.39-fold lower CL/F, and a prolonged t1/2 than A-XY, indicating enhanced bioavailability due to reduced elimination. Furthermore, the tissue distribution revealed that the levels of paeoniflorin and ferulic acid from N-XY significantly increased in liver, spleen, lungs, uterus and ovaries, exhibiting targeting characteristics. CONCLUSION: This study comprehensively explored the formation, characterization, and pharmacokinetics of nano-emulsion in XY pill, introducing novel perspectives and initiating preliminary research on potential SANs in un-decocted traditional Chinese medicine formulations. It also emphasized the importance of enhancing pharmacokinetics of hydrophobic components in Chinese herbal formulations and laid the foundation for future nano-formulation research for XY pill.
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OBJECTIVE:To establish a method for the determination of brucine concentration in plasma of rats,and to compare the pharmacokinetic differences between brucine and its nanostructure lipid carrier (NLC) in rats. METHODS:Sixteen male SD rats were randomly divided into brucine NLC solution group and brucine solution group(using normal saline as solvent, and containing brucine 1.28 mg/mL),with 8 rats in each group. They were given relevant solution 10 mg/kg via tail vein. Blood sample 0.5 mL was collected from fundus venous plexus capillary before medication and 15,20,30,40,45,60,90,120,150, 180,210,240,480 min after medication. HPLC method was adopted. The determination was performed on Dikma C18column with mobile phase consisted of methanol-water containing acetic acid and triethylamine(30∶70,V/V)at the flow rate of 1 mL/min. The detection wavelength was set at 265 nm,and column temperature was 30 ℃. Sample size was 10 μ L. Pharmacokinetic parameters of rats in 2 groups were calculated by using DAS 2.0 software,and the difference of them were compared by F test. RESULTS:The linear range of brucine plasma concentration were 1.03-66.00 μg/mL(R2＝0.999 6);the limit of quantitation was 1.03 μg/mL,and lowest detection limit was 0.515 μg/mL. RSDs of intra-day and inter-day were lower than 5%;method recoveries were 84.90%-100.88%, extraction recoveries were 80.60%-91.98%(all RSDs were lower than 10%). Average plasma concentration-time curve of single administration of brucine NLC solution and brucine solution were all in line with two-compartment model after medication via tail vein. The pharmacokinetic parameters included t1/2αwere(0.24±0.11)and(0.06± 0.03)h;t1/2 βwere (2.90 ± 0.22) and (0.57 ± 0.32)h;AUC0-twere (88.00 ± 6.98) and (28.50 ± 5.87)μg·h/mL;AUC0-∞were (109.96±7.99)and(45.06±6.66)μg·h/mL. Compared with brucine solution group,t1/2 α,t1/2 β,AUC0-tand AUC0- ∞of brucine NLC solution group were increased significantly;while CL, k10and k12were decreased significantly, with statistical significance (P＜0.05 or P＜0.01). There was no statistical significance in k21between 2 groups (P＞0.05). CONCLUSIONS: Established HPLC method is simple, specific,sensitive,precise and highly recoverable. It can be used for the determination of plasma concentration and phamacokinetic study of brucine in rats. After brucine NLC is prepared,the pharmacokinetic parameters of brucine change significantly;retention time of brucine is significantly prolonged and the clearance rate decreases significantly.
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AIM To investigate the tissue distribution of brucine-loaded solid lipid nanoparticles in mice in vivo.METHODS Mice were intravenously injected with suspension of prepared brucine-loaded solid lipid nanoparticles and marked by fluorescein isothiocyanate (FITC).The in vivo tissue distribution of nanoparticles was analyzed by having the brucine contents in various tissues (heart,liver,spleen,lung,kidney and bone) determined by HPLC,after which fluorescence confocal laser endomicroscopy was used for further detection.RESULTS Brucine had its the highest (1.64) relative intake efficiency (Re) in mice liver,and the nanoparticles shared all over one value of targeting efficiencies (Te) in various tissues,manifesting a much stronger selectivity to liver than that of brucine solution.With the extension of time,the FITC-narked nanoparticles displayed a rich extracellular to intracellular distribution indicating a positive correlation.CONCLUSION Brucine's increased distribution in the liver tissue of mice due to its solid lipid nanoparticle form shows obvious for liver targeting.
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Objective To study the process of hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion techniques for osthol. Methods The inclusion complex of osthol and HP-β-CD was prepared by unsaturated water solution and freeze-drying technique. Inclusion techniques were selected by screening on quadratic orthogonal rotation combination design method, and the entrapment efficiency was identified by HPLC. Results The optimal technical conditions were as follows:the ratio of HP-β-CD and drug was 4.5∶1;temperature for electric mixer was 35 ℃;the stirring time for thermostatic waterbath was 210 min. Conclusion This method is reasonable and it may have a prosperous future of development and application.
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OBJECTIVE:To establish a method for determining the main contents and entrapment efficiency in the bruc-ine nanostructured lipid carrier(NLC). METHODS:HPLC was adopted to determine the main content,sephadex gel filtration meth-od was employed to separate free drug in brucine NLC to determine the entrapment efficiency. The column was Dikma C18 with the mobile phase of mobile phase A(methanol)-mobile phase B [water-acetic acid-triethylamine(230∶2.4∶0.3,V/V/V)](30∶70,V/V)at the flow rate of 1 ml/min,the detection wavelength was 265 nm,volume was 10 μl and temperature was 30 ℃. RESULTS:The linear range of brucine was 4.00-80.00μg/ml(r=0.999 9);RSDs of precision,stability and reproducibility tests were≤1.67%;av-erage recoveries of content determination and sephadex gel filtration method were respectively 99.66%(RSD=0.45%,n=9) and 99.75%(RSD=1.74%,n=9);and the average entrapment efficiency was 69.92%. CONCLUSIONS:The method is simple,re-producible and efficient,and can be used for the determination of main contents and entrapment efficiency in brucine NLC.
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AIM: A quantitative method was developed for the determination of deoxyschizandrin and schisandrin B in Liganlong Tablet(Fructus Schisandrae Chinensis,Radix Astragali,Radix Angelicae Sinensis,Radix et Rhizoma seucaulis Acanthopanacis Senticosi,etc.) by HPLC. METHODS: The chromatographic conditions included column Symmetry shield~(TM) RP_(18) 5 ?m,3.9 mm?150 mm,mobile phase: methanol-tetrahydrofuran-water(64∶4∶32),flow rate at 1 mL/min,wavelength at 220 nm. RESULTS: The number of theoretical plates is 3555.5.The Deoxyschizandrin liner is 0.068～0.340 ?g (r=0.999 9) and the Schisandrin liner range is 0.06～0.30 ?g (r=0.999 8).The resolutions are 5.09,1.12,respectively. CONCLUSION: The method is sensitive,quick and accurate for the determination of deoxyschizandrin and schisandrin B in Liganlong Tablet.
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AIM: To investigate the chromatographic fingerprints of Guangyanling Injection(Syringa oblata Lindl) by HPLC. METHODS: The separation was performed on a Water SunFire~ TM C_ 18 4.6 mm?250 mm 5 ?m analytical column with the mobile phase consisting of methanol-water as gradient eluent at the flow rate of 1 mL/min. The UV detection was set at 280 nm. RESULTS: The HPLC-UV fingerprints of Guangyanling Injection was obtained with perfect isolation. CONCLUSION: The fingerprints could be used for the control of Guangyanling Injection.