Objective:To establish a high-performance liquid chromatography (HPLC) for determining the content of levonorgestrel (LNG) and ethinylestradiol (EE) in compound levonorgestrel sustained-release microsphere injection.Methods:C18 column Inertsil ODS-3 (4.7 mm×250 mm, 5 μm) was used. The mobile phase was acetonitrile-water (50∶50, V/V). The flow rate was 1.0 mL/min. The column temperature was 35 ℃. The detection wavelength was 265 nm, and the injection amount was 20 μL. The content of microspheres was determined after validation of HPLC detection methodology.Results:The linear relationship was good in the range of 5.03-201.20 μg/mL LNG, 1.55-61.92 μg/mL EE ( r2=0.999 8). The specificity, precision, recovery, repeatability, stability, etc, met the requirements. The content of LNG in the compound LNG sustained-release microspheres injection was 16.26%, and the content of EE was 2.58%. Conclusion:This HPLC can determine the content of compound levonorgestrel sustained-release injection microspheres, and the method is simple, stable, and has good reproducibility, providing a reference for the determination of levonorgestrel and ethinylestradiol in compound sustained-release preparations.

Objective:To establish a high-performance liquid chromatography (HPLC) for determining the content of levonorgestrel (LNG) and ethinylestradiol (EE) in compound levonorgestrel sustained-release microsphere injection.Methods:C18 column Inertsil ODS-3 (4.7 mm×250 mm, 5 μm) was used. The mobile phase was acetonitrile-water (50∶50, V/V). The flow rate was 1.0 mL/min. The column temperature was 35 ℃. The detection wavelength was 265 nm, and the injection amount was 20 μL. The content of microspheres was determined after validation of HPLC detection methodology.Results:The linear relationship was good in the range of 5.03-201.20 μg/mL LNG, 1.55-61.92 μg/mL EE ( r2=0.999 8). The specificity, precision, recovery, repeatability, stability, etc, met the requirements. The content of LNG in the compound LNG sustained-release microspheres injection was 16.26%, and the content of EE was 2.58%. Conclusion:This HPLC can determine the content of compound levonorgestrel sustained-release injection microspheres, and the method is simple, stable, and has good reproducibility, providing a reference for the determination of levonorgestrel and ethinylestradiol in compound sustained-release preparations.

Objective:To develop an etonogestrel (ENG)/ethinyl estradiol (EE) compound vaginal ring with good sustained-release properties, studying its in vitro release assay methodology, and establishing an accelerated release method with good correlation with real-time release methods. Methods:Ethylene-vinyl acetate copolymer (EVA) was used as the matrix to prepare ENG/EE compound vaginal ring by hot melt extrusion method, and an in vitro real-time release assay method and an accelerated release assay method based on shake flask method were established. The in vitro release behavior and release mechanism of ENG/EE compound vaginal ring were investigated, and the correlation between real-time release and accelerated release over time was analyzed. Results:The obtained vaginal ring had a round appearance and a smooth surface, and the drug was slowly released under the optimal real-time release conditions in vitro (release medium: 200 mL of pure water, shaking at 60 r/min in a constant temperature water bath shaker at 37 ℃), and the cumulative release of ENG and EE on the 21st day were 54.39% and 46.80%, respectively. The correlation coefficients of drug release and its mechanism under the optimized in vitro accelerated conditions (release medium: 200 mL of 0.6% sodium dodecyl sulfate aqueous solution, shaking at 60 r/min at 55 ℃) with the results under real-time release conditions were all greater than 0.99. Conclusion:The ENG/EE compound vaginal ring obtained in this study has a significant in vitro sustained-release effect, and the established accelerated release conditions have a good correlation with real-time release conditions, which can provide a useful reference for the quality evaluation research of such vaginal ring products and the formulation of guidelines for in vitro release research methods.

Objective:To develop an etonogestrel (ENG)/ethinyl estradiol (EE) compound vaginal ring with good sustained-release properties, studying its in vitro release assay methodology, and establishing an accelerated release method with good correlation with real-time release methods. Methods:Ethylene-vinyl acetate copolymer (EVA) was used as the matrix to prepare ENG/EE compound vaginal ring by hot melt extrusion method, and an in vitro real-time release assay method and an accelerated release assay method based on shake flask method were established. The in vitro release behavior and release mechanism of ENG/EE compound vaginal ring were investigated, and the correlation between real-time release and accelerated release over time was analyzed. Results:The obtained vaginal ring had a round appearance and a smooth surface, and the drug was slowly released under the optimal real-time release conditions in vitro (release medium: 200 mL of pure water, shaking at 60 r/min in a constant temperature water bath shaker at 37 ℃), and the cumulative release of ENG and EE on the 21st day were 54.39% and 46.80%, respectively. The correlation coefficients of drug release and its mechanism under the optimized in vitro accelerated conditions (release medium: 200 mL of 0.6% sodium dodecyl sulfate aqueous solution, shaking at 60 r/min at 55 ℃) with the results under real-time release conditions were all greater than 0.99. Conclusion:The ENG/EE compound vaginal ring obtained in this study has a significant in vitro sustained-release effect, and the established accelerated release conditions have a good correlation with real-time release conditions, which can provide a useful reference for the quality evaluation research of such vaginal ring products and the formulation of guidelines for in vitro release research methods.

OBJECTIVE To prepar e and characterize danazol （DAZ）-sodium caseinate （SC）composite nanoparticles ，and to study the mechanism of preparing nanoparticles in “bottom-up”technology. METHODS SC was used as a stabilizer for regulating nanoparticles，so that DAZ-SC composite nanoparticles were prepared by anti-solvent precipitation method. The particle size ， Zeta-potential，micro-morphology，stability，encapsulation efficiency ，drug loading and in vitro dissolution rate were characterized. Fluorescence spectra ，IR spectra ，FBRM and other methods were used to analyze the interaction mechanism between DAZ and SC. RESULTS The particle size of DAZ-SC composite nanoparticles was （223.7±12.5）nm，and the polydispersity index was 0.274± 0.012. Zeta-potential was －（17.81±1.63）mV（n＝3）. The stability of nano-suspension was good ，the solid properties of DAZ were greatly improved ，and the dissolution rate was significantly increased. SC was statically quenched under the action of DAZ and the secondary structures of SC were changed. The crystallization process of DAZ was controlled under the action of SC ，and the interaction between DAZ and SC was mainly hydrogen bond and van der Waals force. CONCLUSIONS In this study ，DAZ-SC composite nanoparticles are successfully prepared. In the “bottom-up”technology，the interaction between SC and DAZ caused by hydrogen bond and van der Waals force inhibits the growth and agglomeration of drug crystals .

OBJECTIVE：To investigate the correlation of storage life and effective composition content with color value of Carthamus tinctorius ，and to provide reference for the quality evaluation of C. tinctorius with different years of storage. METHODS：Using 24 batches of C. tinctorius from same place of production with different years of storage （0，1，2 years，8 batches each type ）as samples ，the contents of hydroxysafflor yellow A （HSYA）and kaempferol were determined by HPLC. Color value [lightness value （L*），red-green value （a*），yellow-blue value （b*）] were determined by spectrophotometer. SPSS 19.0 statistical software was used to analyze the correlation of storage life and effective composition content with color value. RESULTS：Kaempferol content was still high after 1 year or 2 years of storage （0.161％，0.061％，respectively）. However ，the content of HSYA decreased with the prolongation of the storage life （the average content of HSYA were 2.46％，1.58％，and 1.51％ after storage 0，1 and 2 years，respectively），and the color of the drug became darker （a* value decreased ）. Results of correlation analysis showed that the content of HSYA was positively associated with color value L*，a*（r＝0.430，0.781，P＜0.05 or P＜0.01）；the content of HSAY was negatively associated with storage life （r＝－0.777，P＜0.01）. There was no correlation between the remaining variables （P＞0.05）. CONCLUSIONS ：The longer the storage life ，the darker the color and the lower the content of HSYA ，so it is not suitable for over year and multiyear preservation.

To select the most effective parameters of electroacupuncture (EA) at Hegu (LI4) and Sanyinjiao (SP6), a traditional acupuncture formula that induces labor, by comparing its effects on uterine contraction in late-stage pregnant rats, so as to improve the effects of acupuncture on induction of labor and its clinical maneuverability and provide the basis for further mechanism research.

Object To study the preparation and technology on sinomenine (SM) release from Sinomenine Sustained-release Tablets (SSTs) in which hydroxypropyl methyl cellulose (HPMC) was used as the primary excipients. Methods SSTs were prepared with different HPMC viscosity of K4M, K15M, and K100M, different HPMC content, and preparing technology. Results Little effect was observed on the releasing rate of SM with different HPMC viscosity when the content of HPMC was 30%. SM releasing rate increased with the decreasing of proportion of HPMC while the content of HPMC was less than 30%. But the releasing velocity slowed down while the content of HPMC increased and the effect on the releasing rate was not found as the content of HPMC was over 30%. When the ratio of SM and HPMC was 1∶1.5, the releasing rate decreased with the increasing of tablet weight from 280 mg to 360 mg. The releasing rate was insensitive to the particle size of HPMC and hardness of SSTs in this study. Conclusion It is necessary to control the tablet weight and choose the proper quantity of HPMC in the preparation of SSTs.

Object To study the release mechanism of slow released tablet of puerarin (PUE) prepared by taking chistosan (CS) and sodium alginate (AL) as primary excipient. Methods The effect of the release in different conditions and the release mechanism was observed. Results No effect was found on release rate by basket and blade paddle methods, but the primary release (1 2 h) in different rotation speed showed the effect on drug release and the release rate was dependent on medium pH value (P