| Cangai oil is the mixture of oil volatile extracted from seven kinds of traditional chinese medicines including Rhizoma atractylodis, Folium artemisiae argyi, Flos Caryophyllata etc, which based on the clinical recipe prescribed by professor Xiong Lei for preventing upper respiratory tract infection. All of the traditional chinese herbs in this prescription are rich in volatile, and smells fragant, has strong antibacterial effect. Early study show that Cangai oil has good curative effect on lung qi deficiency syndrome. In this paper, inclusion complex/in situ gel composite of Cangai oil was prepared, and the pharmacokinetics in rabbits and the tissue distribution in rats of the composite through nasal delivery were investigated. The purpose is to provide experimental basis for rational screen of administration route and formulation of Cangai oil, and offer the pharmacokinetic datas for later research of Cang Ai volatile oil through nasal administration. The main contents are as follows:1. Preparation and identification for HP-β-cyclo-dextrin inclusion compound of Cangai volatile oilThe inclusion rate and the yield of Cangai volatile oil-β-CD complex were taking as the valuating indicators. By using the saturated water solution method, the orthogonal design was adapted to select the optimum technological conditions.The volatile oil HP-β-CD complex was evaluted by DSC, UV and TLC. The optimum inclusion conditions was as follows: volatile oil: HP-β-CD in proportion as 1:15(m L:g), inclusion temperature of 40℃, mixing time of 3h. Analysis results of DSC,UV and TLC showed that stable inclusion compound had been formed from volatile oil and HP-β-CD.2. Optimization for preparation technology of Cangai volatile oil dextrin inclusion compound/in situ nasal thermosensitive gel by central composite design-response surface methodIn the design, the independent variables were the amounts of poloxamer 407,poloxamer 188, and the dependent variable was the gel temperature. Quadratic models were used to estimate the relationship between the dependent and independent variables, and select the optimal formulations and validation. The quantitative relationships between two factors and valuation index were characterized according to the quadratic polynomial model, and the best dosage of P407 and P188 were 19.37%and 2.73% respectively.3. Study on pharmacokinetics of nasal delivery of Cangai volatile oil and its in dextrin inclusion/in situ gel in rabbitsThe concentration of eugenol that is the main components of Cangai oil in plasma was detected by ultra performance liquid chromatography after intranasal administrating Cangai volatile oil and its dextrin inclusion/in situ gel in rabbits. UPLC determination conditions: Agilent EC-C18 chromatographic column(2.1 mm x 75 mm,2.7 μm), mobile phase: methanol-1% glacial acetic acid(45:55); flow rate: 0.4m L·min-1, The detection wavelength: 280 nm, and the column temperature: 30℃;sample volume: 1 μL. The data were fitted by DAS3.0 software(non-compartment model), and the pharmacokinetic parameters were calculated. The pharmacokinetic parameters of Cangai volatile oil in the blood: Tmax was(0.083±0.000)h; Cmax was(1.15±0.141) mg·L-1; AUC(0-∞) was(0.376±0.085)mg·L-1·h;MRT(0-∞)was(0.505±0.039)h. The primary pharmacokinetic parameters of Cangai volatile oil dextrin inclusion compound/in situ nasal thermosensitive gel in the blood: Tmax was(0.083±0.000)h;Cmax was(4.080±0.467) mg·L-1; AUC(0-∞) was(27.76 ± 6.108) mg·L-1·h-1;MRT(0-∞)was(7.346±1.293) h. The results showed that the AUC and MRT of the dextrin inclusion/in situ gel were significantly different(P<0.01,) compared with cangai oil.It proved that the retention time of the nasal cavity in rabbits was increased,and had a certain sustained-release effect after preparing into dextrin inclusion compound/ in situ gel.4. Study on the tissue distribution of the Cang Ai oil by nasal deliver in the ratsThe content of eugenol in rats’ brain, heart, liver, spleen, lung, kidney were determinated by HPLC method after Cangai oil was administrated by nasal delivery.HPLC conditions: Agilent C18 chromatographic column(4.6 mm x 250 mm, 5 μm),mobile phase: methanol-1% glacial acetic acid(65:35); flow rate: 1 m L·min-1. The detection wavelength: 280 nm; column temperature: 30℃; sample volume: 10 μL.Cangai oil was rapidly distributed to all organizations after intranasal absorption, the content of eugenol in lung tissue was the highest, followed by heart and brain tissue,and the distribution of liver, spleen and kidney was low. |
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