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Objective: To investigate the effect of three types of precipitation inhibitors (PPI) HPMC K4M, HPMC AS MG and Soluplus on the pH-induced supersaturated phase behavior of dl-tetrahydropalmatine (dl-THP) at oral clinical doses. Methods: dl-THP pH solubility phase diagram and desaturation curve during pH-shift were drawn, and the solubility phase diagram was used to support dl-THP phase behavior. Area under the concentration-time curve and supersaturation ratio were used to analyze the effect of PPI on the phase behavior of dl-THP; Polarized light microscope and differential scanning calorimetry were used to analyze the precipitation properties. Results: Under the clinical dosage, the maximum supersaturation of dl-THP during the pH-shift was 3.93, and the supersaturation was lost over time; HPMC K4M, HPMC AS MG, and Soluplus could all maintain the supersaturation within 180 minutes during the pH-shift dissolution. HPMC K4M, HPMC AS MG, and Soluplus maintained supersaturation levels of 1.19, 1.89 and 1.36 respectively at a concentration of 5%, 1.30, 2.35 and 1.86 at a concentration of 20%, and 1.30, 2.60 and 2.07 at a concentration of 50%. Polarized light microscopy and differential scanning calorimetry results showed that crystalline precipitation occurred. Conclusion: All precipitation inhibitors can improve the pH-induced supersaturated phase behavior of tetrahydropalmatine, and this improvement behavior varies with the type and concentration of precipitation inhibitors. HPMC AS MG has the best effect.
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Objective To prepare dl-tetrahydropalmatine (dl-THP) ethosomes (ETS) and elucidate their transdermal absorption properties. Methods Dl-tetrahydropalmatine ethosomes (dl-THP ETS) were prepared by ethanol injection combined with pH-gradient active drug-loading method. Their physicochemical properties including elasticity, vesicle size, morphology and entrapment efficiency were characterized. Franz diffusion cells were used to investigate the ex vivo skin permeation characteristics of the formulation with liposomes (LPS) and tinctures being used as reference preparations. Results According to a preferred formulation of dl-THP ETS [dl-THP 100 mg, vitamin E 1.3 mg, soybean lecithin 1 200 mg, cholesterol 120 mg, absolute ethanol 9 mL and citrate buffered saline (pH 3.0) 21 mL, 0.1 mol/L NaOH solution suitable quantity (to adjust the pH value to 5.5) ], the obtained dl-THP ETS had an elasticity index of (20.1 ± 1.1) mL, an average size of (85.8 ± 0.9) nm with a polydispersity index of (0.082 ± 0.003) and an entrapment efficiency of (81.7 ± 3.2)%. The cumulative permeated drug quantity per unit area (Qn) of dl-THP ETS in 24 h was (2 306.4 ± 592.3) μg/cm2 with no significant difference compared with the Qn of the LPS [(2 434.2 ± 564.4) μg/cm2] (P > 0.05) and about 4 times of that of the tincture [(633.1 ± 218.0) μg/cm2] (P < 0.05). And the averages of RSD of the Qn at each time point were (28.37 ± 10.9)% and (62.83 ± 44.1)% for the ETS and LPS, respectively, indicating that the Qn fluctuation among samples of the ETS was smaller than that of the LPS (P < 0.05). Average correlation coefficients of (0.968 ± 0.033) and (0.882 ± 0.078) (P < 0.05) were obtained for the ETS and LPS respectively when their 24 h permeation curves were fitted to linear relationship, indicating the permeation of the former was closer to zero-order kinetics than that of the latter. Conclusion The dl-THP ETS have a high elasticity, a suitable size, a high entrapment efficiency, and enhanced and stable percutaneous absorption in line with zero-order kinetics.
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Objective: To establish the HPLC fingerprint and multicomponents determination of Corydalis Decumbentis Rhizoma, and provide a scientific basis for the improvement of its quality standards. Methods The separation was performed on a chromatographic Diamonsil C18 column (250 mm × 4.6 mm, 5 μm), with acetonitrile-0.2% acetic acid (adjusting pH to 6.0 with triethylamine) as the mobile phase for gradient elution. Volume flow rate was 1.0 mL/min. Column temperature was 35 ℃. Injection was 10 μL and the detection wavelength was 280 nm. The fingerprints of 15 batches of Corydalis Decumbentis Rhizoma were established and evaluated by the similarity evaluation system of TCM (version 2012A), which were divided into two categories by clustering analysis and principal component analysis. Meanwhile, the content of protopine, palmatine, bicuculline and tetrahydropalmatine was determinated. Results:The fingerprint of Corydalis Decumbentis Rhizoma was established. There were 10 common peaks in the fingerprint. Protopine, palmatine, bicuculline and dl-tetrahydropalmatine were separated with good linearity relationships (r > 0.999 9). The average recovery rates of the investigated compounds were 97.12%, 100.09%, 98.53%, and 99.71%, respectively. Conclusion:HPLC fingerprint combined with multicomponents determination can provide the reference for the quality evaluation of Corydalis Decumbentis Rhizoma.
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Objective: To establish a method of HPLC for simultaneous determination of six ingredients in Yuanhu Zhitong Dripping Pills. Methods: Separation was performed on a Diamonsil C18 column (250 mm × 4.6 mm, 5 μm); Mobile phase was acetonitrile (A)-0.04% ammonium acetate (acetic acid tone pH 4.0) (B), gradient elution: 0-10 min, 20% A, 10-25 min, 20%-25% A, 25-70 min, 25%-75% A; flow rate was 1 mL/min; column temperature was 35 ℃; detection wavelength was 280 nm; and injection volume was 10 μL. The contents of dl-tetrahydropalmatine, palmatine, dehydrocorydaline, d-corydaline, imperatorin, and isoimperation were determined. Results: The linear ranges were 14.94-149.40 μg/mL for dl-tetrahydropalmatine, 1.97-19.72 μg/mL for palmatine, 15.94-159.36 μg/mL for dehydrocorydaline, 9.72-97.20 μg/mL for d-corydaline, 2.82-28.17 μg/mL for imperatorin, and 0.61-6.06 μg/mL for isoimperation, respectively, with the correlation r > 0.999 0. The extraction recoveries varied from 95% to 105% (RSD varied from 1.82% to 2.99%). The contents of dl-tetrahydropalmatine, palmatine, dehydrocorydaline, d-corydaline, imperatorin, and isoimperation was 0.368-0.483, 0.058-0.082, 0.532-0.766, 0.315-0.459, 0.145-0.212, and 0.030-0.053 mg/g, respectively. Conclusion: The method is accurate and reliable, which can be used for the quality control of Yuanhu Zhitong Dripping Pills.
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Objective: To study the enzymatic reaction kinetics of dl- tetrahydropalmatine (TET) in total alkaloid (TA) of Corydali Rhizoma in rat liver microsomes and to investigate the compatible effects of the effective components such as coumarin (Cou) and volatile oil (VO) in Angelicae Dahuricae Radix with TA in Corydali Rhizoma on enzymatic reaction kinetics of TET. Methods: Rat liver microsomes were prepared by ultracentrifugation and the TET concentration in incubation medium was determined by HPLC. Comparative study on the enzymatic reaction kinetics of TET in each group of TA, TA-Cou, TA-VO, and TA-Cou-VO to deduce the michaelis constant (Km) and maximum reaction rate (Vmax) of TET in each group and calculate the clearance rate (CLint) of TET in each group. Results: The Km, V max, and CLint in TA group were 0.12 μmol/ (L·min·mg), 5.40 μmol/L, and 0.022 L/(min·mg), respectively; In TA-Cou group they were 0.27 μmol/(L·min·mg), 40.18 μmol/L, and 0.006 L/(min·mg), respectively; In TA-VO group they were 0.57 μmol/(L·min·mg), 22.60 μmol/L, and 0.025 L/(min·mg), respectively; In TA-Cou-VO they were 0.84 μmol/(L·min·mg), 23.25 μmol/L, and 0.036 L/(min·mg), respectively. Conclusion: The effective components of TA in Corydali Rhizoma with Cou and VO in Angelicae Dahuricae Radix could decrease CLint of TET in TA of liver.
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AIM: To study the determination of dl-tetrahydropalmatine (THP) in Chi nese traditional patent medicines by TLC-Scanning from the viewpoint of the pro cess control of manufacture. METHODS: To select the 5 kinds of representative drugs and its prep arations contained, THP was extracted with solvent method. The mobile phase contains diethylamine. THP w as separated with high-efficiency silica gel plate or handcrafted silica gel p late. Iodine was used for chronogenic agent and fluorescence defectiion for dete rmination. TLC-Scanning results were compared with HPLC. RESULTS: The method is practicable, the result is correlative with the HPLC. CONCLUSION: TLC-Scanning is fit for the quality control of the Chi nese traditional patent medicine in the process of manufacture.
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AIM: To establish a RP-HPLC method for simultaneous determination of the dl-tetrahydropalmatine and imperatorin in Yuanhu Zhitong Prescription (Rhizoma Corydalis, Radix Angelicae Dahuricae). METHODS: dl- tetrahydropalmatine and imperatorin were extracted with ether and determined by HPLC using a BDS C 18 column(5?m,4.6?250mm),phosphate buffer(pH6.6)-methanol(39∶61) as a mobile phase. The mobile rate was at 1mL?min -1 and detection wavelength was at 280nm. RESULTS: The relationship between the concentration and the peak area of dl-tetrahydropamaltine and imperatorin were good linear relation, respectively. Either of correlation coefficient approached 0.999. CONCLUSION: This method can be used to determine the concentration of dl-tetrahydropalmatine and imperatorin in the preparation of Yuanhu Zhitong Prescription.
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Dl-tetrahydropalmatine (THP) 5 ~ 15 mg ? kg-1 iv markedly reduced the incidences of cardiac arrhythmias and myocardial lipidperoxide content after reperfusion of the is-chemic myocardium in rats. In isolated rat ventricular muscles, THP 1,3 and 10 ?mol?L-1 shifted the concentration-effect curves for phenylephrine to the right unparally, together with decreasing their maximal responses,exhibiting a non-competed antagonistic action. It was also found that THP 10 ?mol?L-1was able to reduce the amplitude of delayed afterdepolar-izations and to stop triggered activity and/or ab-normal automatic activity induced by reoxygena-tion of hypoxic myocardium in isolated ventricular muscles of guinea pig. These results suggest that the protective effects of THP might be attributed, at least in part, to the depression of delayed afterdepolarizations and the prevention of oxygen free radical injury without the involvement of the cardiac ?1-adrenoceptors.
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The effects of DL-tetrahydropalmatine andsinomemine on the activity of oviduct smooth mus-cle and ovum transport in rabbits are reported inthis paper. The results indicate that the two a-gents apparently inhibit the contractile activity ofoviduct isthmic smooth muscle of rabbit in vitroand decrease the frequency, amplitude, tensionand curve areas of the contraction. The contractileffect induced by noradrenaline is also inhibited re-markbly by them. In addition, DL-THP and Sino.can delay ovum transport in rabbit oviduct after ivHCG 48 h. It is suggested that the inhibition ofactivity of oviduct smooth muscle may be one ofthe important causes of delaying egg transportcaused by the two agents.