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Besides cultivation, extraction is also a critical stage in enhancing the yield of phycocyanin production - a highly valuable compound from Spirulina biomass. In this study, the combined effect of three important variables in the ultrasonic-assisted extraction process on phycocyanin extraction yield, namely extraction temperature, sonication time, and solvent pH were investigated through a central composite design experiment. Furthermore, the response surface method was applied in order to define an optimal condition to achieve the highest extraction yield. The results showed that when temperature ranged from 35ºC to 45ºC, sonication time from 20 to 50 minutes, and solvent pH from 6 to 8, the average yield of 30.135±1.552 mg/g was obtained with an average purity of 0.871±0.043. A regression model was also successfully developed, which allowed a good prediction of extraction yield based on the three mentioned variables. On the other hand, an optimal condition for extraction was also proposed with sonication time = 43.57 minutes, extraction temperature = 37.6oC, and solvent pH = 6.7. These results were practically valuable for the improvement of phycocyanin extraction from Spirulina biomass
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OBJECTIVE To optimize the extraction process of polysaccharides from Dendrobium officinale， and preliminarily study its effect on acute lung injury （ALI） in mice. METHODS Using D. officinale as raw material， the polysaccharides were extracted from D. officinale by ultrasonic-assisted hot water immersion. Using the extraction rate of D. officinale polysaccharides as response value， the single-factor experiments and Box-Behnken response surface method were used to optimize the ratio of material to liquid， extraction time and extraction temperature. ALI mice were induced by lipopolysaccharide. Using prednisone acetate （5 mg/kg） as the positive control， the effects on the mass ratio of wet and dry lung and pathological changes of lung tissue （HE staining and Masson staining） of low-dose， medium-dose and high-dose D. officinale polysaccharides （50，100，200 mg/kg） were investigated. RESULTS The optimal extraction technology of D. officinale polysaccharides was as follows： the ratio of material to liquid was 1∶25 （g/mL）， the extracting time was 1 h， and the extracting temperature was 58 ℃ . Under these conditions， the average extraction rate of D. officinale polysaccharides was 37.75% （RSD＝1.12%，n＝3）， the relative error of which with predicted value （38.63%） was 2.28%. Compared with the model group， the ratios of wet and dry lung in the positive control group and D. officinale polysaccharides groups were all decreased significantly （P＜0.05 or P＜0.01）， and the pathological changes in lung tissue （severe destruction of alveolar structure， significant widening of alveolar septa， extensive infiltration of inflammatory cells and proliferation of fibroblasts） were alleviated to varying degrees. CONCLUSIONS The optimal extraction process of D. officinale polysaccharides is feasible； the obtained polysaccharide extract has a certain improvement effect on ALI in mice.
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OBJECTIVE To optimize the extraction process of blumeatin from Blumea balsamifera and to evaluate its antibacterial and anti-inflammatory activity. METHODS The content of blumeatin in the extract of B. balsamifera was determined by HPLC. On the basis of the single factor experiment， the extraction technology of blumeatin was optimized by the Box-Behnken response surface method with the volume fraction of ethanol， liquid-solid ratio and extraction time as the factors， using the yield of blumeatin as index. Microdilution method was used to determine the antibacterial activity of blumeatin against Streptococcus pyogenes， Staphylococcus aureus， Streptococcus agalactiae， Streptococcus mutans， Bacillus subtilis and Micrococcus luteus. The anti-inflammatory activity of blumeatin was evaluated by ear swelling test and capillary permeability test in mice. RESULTS The optimal extraction technology was as follows： ethanol concentration of 90%， liquid-material ratio of 15∶1， extraction time of 2 h at 80 ℃； the yield of blumeatin using this extraction process was 1.97 mg/g. The minimum inhibitory concentrations of blumeatin for S. pyogenes， S. aureus， S. agalactiae， S. mutans， B. subtilis and M. luteus were 50.00， 200.00， 400.00， 400.00， 800.00 and 1 600.00 μg/mL， respectively； the minimum bactericidal concentrations of blumeatin for S. pyogenes and S. aureus were 400.00 and 1 600.00 μg/mL， respectively. Blumeatin could significantly inhibit the ear swelling induced by xylene and capillary permeability induced by acetic acid in mice（P＜0.05 or P＜0.01）. CONCLUSIONS The optimized extraction technology of blumeatin is stable and feasible. The extracted blumeatin has a certain antibacterial effect against S. pyogenes and a good anti-inflammatory activity.
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OBJECTIVE To optimize the extraction process of Sarcandra glabra. METHODS The contents of rosmarinic acid and isofraxidin in S. glabra were determined by HPLC； ultrasonic time， ultrasonic temperature， solid-liquid ratio （mL/g） and methanol volume fraction were investigated by single factor test. Based on the results of single factor test， experimental scheme was designed by Box-Behnken response surface method， and the entropy weight method was used to assign the weight of each index and calculate the comprehensive score. Taking the comprehensive score as the evaluation index， the extraction process of S. glabra was optimized， and then optimized extraction process was verified. RESULTS The optimal extraction technology of S. glabra included ultrasonic time of 40 min， ultrasonic temperature of 45 ℃， liquid-solid ratio of 50∶1， methanol volume fraction of 70%. The results of 3 times of verification experiment showed that average comprehensive score was 0.988 6， and the RSD was 0.50%. The deviation between the actual value and the predicted value （0.985 1） of each comprehensive score was within ±1%. CONCLUSIONS The optimized extraction method is stable， feasible and repeatable， which can provide reference for extraction of S. glabra.
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OBJECTIVE To optimize the water extraction process of Maxing kechuan granules. METHODS With the contents of ephedrine hydrochloride， bergenin， prim-O-glucosylcimifugin， 5-O-methylvisamin， naringin and hesperidin and the rate of extraction as the evaluation indexes， the weight was determined by the analytic hierarchy process（APH）-entropy weight method， and the comprehensive score was calculated as the response value. Based on the single-factor test， the Box-Behnken response surface method was used to investigate the factors， and the best water extraction process of Maxing kechuan granules was optimized； process validation was also carried out. RESULTS The best water extraction process of Maxing kechuan granules optimized was as follows： soaking for 40 minutes， adding 8 times water， and extracting for 180 minutes. After three validation tests， the comprehensive score was 94.82 （RSD＝0.96%， n＝3）， which had a small difference from the predicted value of 94.64. CONCLUSIONS The water extraction process of Maxing kechuan granules is stable and reliable， which can provide a reference for the development of the preparation.
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Objective To prepare berberine hydrochloride nanoemulsion, optimize its formulation composition and preparation process, and investigate its in vitro characteristics. Methods BBR-NE was prepared by water drop addition and pseudo-ternary phase diagram was drawn. The formulation of NE was optimized by central composite design-response surface methodology to choose the optimal formulation composition. The particle size, potential and appearance of the prepared BBR-NE were characterized. Results The optimal prescription of BBR-NE was determined as the oil phase Capryol 90 accounted for 32.84% of the system, the surfactant Tween-80 accounted for 33.90%, the co-surfactant 1,2-propylene glycol accounted for 16.95%, and water relative system accounted for 15.25%. The prepared NE was clear and transparent in appearance, regular in shape and uniform in size, with an average particle diameter of (68.85±8) nm, polydiseperse index of (0.245±0.03) and drug loading of 0.83 mg/g. The in vitro drug release results of NE showed that the in vitro drug release behavior was passive diffusion, which had a certain slow releasing effect and met the first-order release equation. Conclusion The BBR-NE can provide a new dosage form for the clinical use of berberine.
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Objective:To optimize the ethanol reflux extraction process of total saponins in total saponins of Trillium tschonoskii Rhizome. Methods:On the basis of single factor tests, making the total extraction rate of three main compounds [paris saponin Ⅵ, paris saponin Ⅶ and pennogenin-3- O-α-L-rhamnopyranosyl-(1→4)-[O-α-L-rhamnopyranosyl (1→2)]- O-β-D-glucopyranoside (PRRG)] as the indicator, the optimal extraction parameter was selected with the main influencing factors: the ethanol concentration, solid-liquid ratio, and extraction time by the central composite design-response surface method.Results:The optimal extraction parameter for the ethanol extract of total saponins of Trillium tschonoskii Rhizome was as follows: ethanol concentration 69%, extraction time 1.9 h, and solid liquid ratio 1∶9.7. The binomial fitting complex correlation coefficient r = 0.966 1, and the deviation between the extracted predicted value and the actual value is 4.68%. Conclusion:The central composite design-response surface method is simple and reliable for the optimization of extraction process of total saponins of Trillium tschonoskii Rhizome.
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This research was used with high performance liquid chromatography(HPLC), combined with information entropy-response surface method(RSM) to investigate the ethanol concentration, extraction time, liquid-to-material ratio. Taking the content of four chromogens as evaluation indexes, the weight coefficients of each index were given, and the comprehensive score was calculated to optimize the extraction process. Then, prim-O-glucosylcimifugin was used as the reference, the relative calibration factors(RCFs) of cimifugin, 4'-O-β-D-glucosyl-5-O-methylvisamminol and sec-O-glucosylhamaudo to prim-O-glucosylcimifugin were calculated respectively. The contents of four components in Saposhnikoviae Radix were determined by both external standard method(ESM)and quantitative analysis of multi-components by single marker(QAMS) method, and the results were compared. At last, combined with principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) to evaluate the quality of the Saposhnikoviae Radix in different production areas. The optimal extraction process parameter of the Saposhnikoviae Radix was as follows: liquid-to-material ratio is 60∶1(mL·g~(-1)), extraction time is 35 min, and ethanol concentration is 70%. The repeatability of the RCFs was perfect, and the results calculated by the QAMS were consistent with the results from the ESM. The stoichiometric results indicate that there are obvious differences in the distribution of Saposhnikoviae Radix in different production areas, and cimifugin and prim-O-glucosylcimifugin are the characteristic compounds that cause this difference. In this study, the optimal extraction process is stable and feasible, and the method of QAMS is accurate and reliable. From the perspective of four chromogens, there are differences in the quality of the Saposhnikoviae Radix in different production areas. Therefore, the established extraction process combined with the method of QAMS can be used to evaluate the quality of Saposhnikoviae Radix and provide a scientific basis for the quality control of Saposhnikoviae Radix.
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Apiaceae , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Entropy , Plant RootsABSTRACT
【Objective】 To optimize the purification conditions of heparin affinity chromatography in the purification of human coagulation factor Ⅸ by response surface method and establish the optimal chromatography process parameters. 【Methods】 The effect of sample loading temperature on purification efficiency was analyzed through single factor test. Three-factor three-level response surface method was used to optimize the chromatographic elution conditions. The Folin phenol method and the automatic hemagglutination analyzer were used to determine the total protein content and human coagulation factor Ⅸ titer, respectively. The purification effect was evaluated by activity index and process recovery rate. 【Results】 The optimized optimal chromatographic conditions were loading at 5 ℃, washing 4 CV, eluent formulation of sodium citrate 20 mmol/L, arginine hydrochloride 18.7 mmol/L, NaCl 611.6 mmol/L and pH 7.5; under this optimal setting, the recovery rate of the chromatographic process was (46.6±2.9) %, titer of factor Ⅸ rated to (68.4±4.7) IU/mL and specific activity was (62.8±3.3) IU/mg. 【Conclusion】 The optimized parameters of heparin affinity chromatography process by response surface method can produce better purification effect on human coagulation factor Ⅸ.
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Objective:To optimize the preparation technic of Chuanxiong Rhizoma with vacuum steam method, and to investigate the anti-inflammatory and analgesic activity of Chuanxiong Rhizoma decoction pieces with Central Composite Design-Response Surface Method. Methods:Taking the content of ferulic acid as the evaluation index and the moistening temperature, moistening time and vacuum time as the observation indexes, the moistening technic of Chuanxiong Rhizoma was optimized by Response Surface Method, and selected the optimized plan. The anti-inflammatory and analgesic activities of Chuanxiong Rhizoma were investigated by auricle swelling induced by xylene and writhing induced by glacial acetic acid. Results:The optimum vacuum moistening technic was that the softening temperature was 80 ℃, the softening time was 50 min and the vacuum time was 45 min. The content of ferulic acid in Chuanxiong Rhizoma produced by this technic is highand could decreased the times of wrinkle reaction induced by acetic acid in mice, prolonged the latent period, and obviously or partially inhibitied the ear swelling degree induced byxylene in rats. Conclusions:The Response Surface Method technic of Chuanxiong Rhizoma is easy to operate with high accuracy. The vacuum steam treatment was more obvious than traditional technology group. It provides reference for the subsequent production of Chuanxiong Rhizoma decoction pieces and have the certain value for its promotion and application.
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Objective:Response surface methodology was used to optimize the optimal extraction conditions of red ginseng polysaccharide and to study the antioxidant activity of red ginseng polysaccharide.Methods:Supercritical CO 2 extraction method was used to extract polysaccharides from red ginseng. The effects of solid-liquid ratio, extraction time, extraction temperature and extraction pressure on the extraction of polysaccharides from red ginseng were investigated. Box-behnken Design method was used to optimize the extraction process of red ginseng polysaccharide, and Logit method was used to calculate the semi-inhibitory concentration of red ginseng polysaccharide on DPPH clearance (half maximal inhibitory concentration, IC 50). Results:The optimal extraction conditions were as follows: extraction temperature 61.12 ℃, extraction pressure 20.64 MPa, extraction time 128.37 min, solid-liquid ratio 1∶25.61 g/ml, and the extraction yield of red ginseng polysaccharide was 36.89%. The results of three groups of repeatability tests showed that the relative error of polysaccharide yield of red ginseng was in the range of 5%. When the mass concentration of red ginseng polysaccharide was 25 μg/ml, it had better antioxidant activity and IC 50 was 10.97 μg/ml. Conclusion:The optimized extraction conditions of red ginseng polysaccharide were reasonable and reliable, and the antioxidant activity of red ginseng polysaccharide was strong, which could provide reference for the follow-up research.
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OBJECTIVE：To optimize the formulation of Curcumin （CUR）transethosomes（CUR-TEs）. METHODS ：The contents of CUR in CUR-TEs were determined by HPLC. CUR-TEs were prepared by injection method. Using comprehensive score of encapsulation efficiency and drug loading as index ，based on signal factor test ，Box-Behnken design-response surface method was used to optimize and validate the formulation. The property of CUR-TEs prepared by the optimal formulation was investigated. RESULTS：The optimal formulation of CUR-TEs was as follows as lecithin of 4％，CUR of 0.13％，1，2-propylene glycol of 25％，tween-80 of 1％. Results of validation test of optimal formulation showed that comprehensive score of encapsulation efficiency and drug loading of CUR-TEs was 93.04±2.16，relative error of which to predicted value （91.19）was 2.03％. The encapsulation efficiency of CUR-TEs prepared by optimal formulation was （91.17±1.35）％，and its drug loading was （0.94± 0.02）％. The particle size was （190.64±15.97）nm with polydispersity index of 0.086±0.007，and Zeta potential was （－12.74± 1.60）mV. CONCLUSIONS ：The optimized formulation of CUR-TEs is stable ，feasible and repeatable ，with good stability.
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OBJECTIVE：To optimize the honey-stir-fried technology of Chelidonium majus . METHODS ：Taking the mass ratio of water to honey ，the ratio of honey water to C. majus ，stir-fired temperature ，stir-fired time as the factors ，the total contents of chelidonine ，coptisine hydrochloride ，sanguinarine，berberine，chelerythrine as response values ，Box-Behnken response surface method was used to optimize the processing technology ，and valifation test was conducted. RESULTS ：The optimum process conditions were as follows the ratio of water to refined honey 1∶1.9（g/g），the ratio of honey water to C. majus 21∶100（g/g）， stir-fried temperature 122 ℃，stir-fried time 10.40 min. After 3 times of validation ，average total contents of 5 components was 10.37 mg/g（RSD＝0.23％），relative error of which with predicted value （10.39 mg/g）was 0.19％. CONCLUSIONS ：The optimized honey-stir-fried technology of C. majus is stable and feasible.
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OBJECTIVE: To prepare simvastatin tablets and optimize its formulation by 3D printing technology. METHODS: A cylindrical tablet with a radius of 4 mm and a thickness of 4.8 mm were prepared by a 3D printer. The dosage of the adjuvant povidone 30(PVP K30), lactose/microcrystalline cellulose (MCC) and absolute ethanol were taken as an investigation factor, the cumulative dissolution rate of 5, 15 and 30 min were used as an evaluation index,and the central composite design-response surface method was used to optimize the formulation and verify, the effect of dissolution were researched by compared with the traditional preparation. RESULTS: The optimal formulation value: the ratio of PVP K30 was 30%, the mass ratio of lactose/MCC was 2.5, the ratio of absolute ethanol was 74%, and the cumulative dissolution in vitro of the printed tablets at 5, 15, 30 min was (45.7±0.5)%, (70.9±0.7)%, (89.7±2.3)% respectively, the deviation between the verification result and the predicted value were less than 5%. The preparation of dissolutioncurve is similar with commercially available formulations. CONCLUSION: The successful preparation of 3D printed simvastatin tablets is simple and the mathematical model is predictive.
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Objective: To optimize the extraction process parameters of Guizhi Shaoyao Zhimu Granules (GSZG). Methods: Using high performance liquid chromatography and Elisa, the extraction rate of trans-cinnamaldehyde, paeoniflorin, mangiferin, glycyrrhizic acid, the dry extract yield of extracted herbs and inflammatory factor IL-6 were comprehensively evaluated. The information entropy weighting method was used to determine the objective weight of each index, and response surface methodology was adopted to optimize the extraction process parameters of GSZG. Results: The method had good linear relationship within the range of 3.27-104.64 μg/mL for trans-cinnamaldehyde (r = 0.999 9), 8.16-261.03 μg/mL for paeoniflorin (r = 1.000 0), 1.39-89.27 μg/mL for mangiferin (r = 0.999 9), and 1.00-33.00 μg/mL for glycyrrhizic acid ammonium salt (r = 0.999 9). Guizhi-Shaoyao-Zhimu extraction had the effect of inhibiting the proliferation of MH7A cells (molded by TNF-α) with IC50 of 1.02 mg/mL, and had anti-inflammatory activity. Entropy method was more scientific, reasonable and stable. According to the comprehensive scoring results and practical situation, it was determined that the best extraction process of the preparation was to add 16 times the amount of water, and decocted three times for 1 h each time. The RSD of the predicted value was less than 3% compared with the measured value. Conclusion: The preferred process has high extraction rate, with good stability and repeatability, which is suitable for the mass production of GSZG.
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Objective: To optimize the prescription process of curcumin-piperine polymeric compound micelles (Cur/Pip F127/P123-PM) by central composite design-response surface method. Methods: The content of curcumin and piperine was determined by UPLC. The Cur/Pip F127/P123-PM was prepared by thin film hydration method. Based on the single factor test, the dosage, the mass ratio of F127 and the volume of water were used as independent variables, and the drug loading and entrapment efficiency of curcumin, entrapment efficiency of piperine and the micelle size were dependent variables, and next central composite design-response surface method of three factors and five levels was carried out. The analysis results showed and verified the optimal prescription. Finally, the optimal lyophilization conditions of the micelle preparation were initially screened. Results: The optimal preparation process was as follow: the dosage of curcumin and piperine was 12.96 mg and 0.69 mg, respectively; The mass ratio of F127 was 0.46, and the volume of water was 8.85 mL. The compound curcumin micelles prepared by the optimum formulation had the loading capacity of 5.63%, solubility of 1.27 mg/mL and entrapment rate of curcumin was 86.86%. The entrapment rate of piperine was 77.54%; The micelle size was 66.79 nm and the Zeta potential was close to zero. The lyophilized products prepared by using 8% mannitol as a protective agent had a good redispersion. Conclusion: The model established by central composite design-response surface method can be used to optimize the prescription of compound curcumin micelles, and the method had a high accuracy and good predictability advantage.
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Objective: To optimize the formulation of 1,8-cineole self-microemulsifying drug delivery system (1,8-Cin-SMEDDS), characterize it and investigate its cell uptake. Methods: By drawing pseudo-ternary phase diagram, the effective self-emulsifying region of 1,8-Cin-SMEDDS was determined, and the preliminary prescription was screened. Taking the particle size and drug loading as the index, the central composite design-response surface method was used to optimize and verify the prescription. Fluorescence microscope was used to observe the uptake of human umbilical vein endothelial cells (HUVEC) injured by high glucose. Results: The results showed that the best prescription of 1,8-Cin-SMEDDS was a mixture of soybean oil (7.5%) and 1,8-Cin (22.5%), HS15 (56%) as emulsifier, ethanol (14%) as co-emulsifier, and dripping pure water to 8 mL to obtain a translucent slightly bluish emulsion. The appearance of spherical droplets was observed by transmission electron microscope, and the average particle size and Zeta potential measured by laser particle size Zeta tester was (131.68 ± 1.44) nm and (-10.03 ± 1.63) mV, respectively; The entrapment efficiency estimated by HPLC was (99.890 ± 0.012)%, and the drug loading was (224.750 ± 0.028) mg/g. The results of HUVEC cell uptake assay showed that the uptake of 1,8-Cin-SMEDDS by cells was higher than that of free 1,8-Cin. Conclusion: The preparation method of 1,8-Cin-SMEDDS is simple and reproducible. The obtained method has good appearance, high entrapment efficiency, stable physical, and chemical properties, which can also promote cell uptake.
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Objective: To optimize the prescription and preparation process of "Hugan I" Orally Disintegrating Tablets, and investigate its efficacy against acute liver injury in mice. Methods: Single factor method was used for disintegrants, lubricants, and fillers screening. Taking the appearance, hardness, friability and disintegration time of the tablets as the comprehensive evaluation index, the dosage of disintegrant, micro-silica gel and magnesium stearate was selected as the investigation factor. The Box-Behnken response surface method was used to optimize the orally disintegrating tablets. Acetaminophen (APAP, 500 mg/kg) was used to replicate acute liver injury model by one-time high-dose intragastric administration to investigate the effects of orally disintegrating tablets on the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, the content of glutathione (GSH) and malondialdehyde (MDA) and morphological changes in liver tissue. Results: The optimal prescription was as following: dry paste powder 22.00%, microcrystalline cellulose 18.00%, sorbitol 20.00%, mannitol 16.00%, Aspartame 0.50%, citric acid 0.50%, disintegration agent L-HPC 20.00%, micro-powder silica gel 2.50% and magnesium stearate 0.50%. The hardness of the orally disintegrating tablets was 4-7 kg, the mean disintegration time was about 50 s, and the mean friability was around 0.85%. Compared with the model group, there were significant differences (P < 0.01) in Biphenyl diester control group, "Hugan I" Decoction group and "Hugan I" Orally Disintegrating Tablets group, and the levels of ALT and AST in the serum of the mice were significantly decreased, The content of MDA in the liver tissue was decreased, which improved the damage of APAP to liver tissue. Conclusion: The formulation of the "Hugan I" Orally Disintegrating Tablet is feasible and easy to operate, which achieves the same effect with "Hugan I" Decoction that effectively prevent liver damage caused by acetaminophen with no significant differences.
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Objective: Puerarin nanoemulsion (Pue-NE) was prepared with glycyrrhizic acid as a natural stabilizer, and its release characteristics in vitro were investigated. Methods: Data processing was performed using particle size and polydispersity index (PDI) as independent variables, and using the overall desirability (OD) as the evaluation index. The central composite design-response surface method was used to optimize the prescription, and the physical and chemical properties and release characteristics of Pue-NE prepared by the optimal prescription were investigated. Results: The best prescription for Pue-NE is puerarin at a concentration of 5.0 mg/mL, glycyrrhizic acid at a concentration of 1.75 mg/mL, and caprylic glyceride in an amount of 3.5 mL. The average particle size of the nanoemulsion is (184.5 ± 0.8) nm, the PDI is 0.088 ± 0.002, the zeta potential is (10.56 ± 0.35) mv, the conductivity is (98.3 ± 0.4) μs/cm, pH is 6.750 ± 0.005, solubility (4.970 ± 0.008) mg/mL, drug loading is (99.4 ± 0.2)%, turbidity (24.3 ± 1.0) cm-1 (n = 3). It was identified as O/W emulsion by dyeing method. TEM scanning results show that the droplets are spherical and uniform in size and the stability results showed that Pue-NE has good storage stability at 25 ℃. In vitro release results showed that Pue-NE has the greatest release in phosphate buffered pH 6.8 within 24 hours. Conclusion: The preparation of Pue-NE with glycyrrhizic acid as a natural stabilizer is not only simple and convenient, but also can effectively replace the use of traditional chemical synthetic stabilizers and improve the solubility of puerarin.
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Objective: To optimize the formulation of paeonol lipid microspheres (Pae-LM) through central composite design- response surface method and determine its in vitro release characteristics. Methods: Using the mean particle size and centrifugal stability constant (Ke) as evaluation indexes, the oil phase type and the ratio of composite oil, the amount of phospholipid and stearic acid, the type of emulsifier, the type and amount of stabilizer, the quality of PC and CH, the high-speed shear temperature and time, the homogenization pressure and time was screened in prescription process. Effects of dosage of paeonol and high pressure homogenizing pressure on the properties of Pae-LM preparation were investigated by central composite design-response surface method. The binomial model and multivariate linear regression model were used to establish the mathematical relationship between the indexes and the factors. According to the best mathematical model of evaluation index, the response surface was depicted and the best prescription was analyzed by the response surface method. According to the optimized formulation Pae-LM, the in vitro drug release characteristics were investigated. Results: The best prescription of Pae-LM was basically round, with mean particle size of (149.32 ± 0.57) nm, Zeta potential of (-36.01 ± 3.09) mV, encapsulation rate of (98.24 ± 0.32)% and drug-loading rate of (11.94 ± 0.04)%. There was a credible quantitative relationship between Ke and the two factors, and the binomialmodel was more reliable than the multivariate linear model. The cumulative release of paeonol drug substance at 12, 24 and 36 h were 71.84%, 85.21% and 95.07%, while the cumulative release of Pae-LM was only 57.21%, 59.66%, and 63.91% at 12, 24 and 36 h, respectively. The drug release was in accordance with the Ritger-peppas model. Conclusion: Central composite design-response surface method can be applied to optimize prescription of lipid emulsion microspheres. The optimized particle size of Pae-LM was suitable with a higher encapsulation rate, which can provide a reference for the development of paeonol cardiovascular delivery system.