OBJECTIVE To prepare polymyxin B sulfate multivesicular liposomes (PMB-MVLs), optimize their formulation, and their quality, stability, release and investigate their antibacterial activity in vitro. METHODS The PMB-MVLs were prepared by the double-emulsion method. The response surface method of Box-Behnken design was used to optimize the initial prescription. High performance liquid chromatography method was established to quantitatively analyze PMB in PMB-MVLs. The physicochemical properties, the in vitro drug release behavior, in vitro antimicrobial activity and formulation safety of PMB-MVLs were investigated. RESULTS The appearance of PMB-MVLs prepared by optimal prescription were non-concentric spherical vesicles with uniform size. The encapsulation efficiency of PMB-MVLs were (69.521±1.531)%. The average particle size was (5.84±1.42) μm, and the average Zeta potential was (-26.77±0.55)mV. The PMB-MVLs showed good stability when stored at 4 ℃ for one month. The results showed that PMB-MVLs were released continuously for 72 h in vitro, and there was no sudden release effect. The in vitro antibacterial activities of PMB-MVLs on E.coli and P.aeruginosa were significantly stronger than those of the free PMB. And PMB-MVLs has no risk of hemolysis within its range of antimicrobial activity. CONCLUSION The slow-release PMB-MVLs are successfully prepared with uniform particle size, high encapsulation efficiency, and enhanced antibacterial activity.

OBJECTIVE To explore the development of maximum residue limit standards for pesticides in Atractylodis Macrocephalae Rhizoma that conform to the characteristics of traditional Chinese medicine use. METHODS The samples were processed by QuEChERS method, and a combination of GC-MS/MS and LC-MS/MS was used to screen and determine 99 pesticide indicators in Atractylodis Macrocephalae Rhizoma. At the same time, the sensitivity, recovery rate, reproducibility, and precision of the method were verified. A risk assessment model and transformation principle that conforms to the characteristics of traditional Chinese medicine were adopted to determine the indicators and limits of the pesticide limit standards for Atractylodis Macrocephalae Rhizoma. RESULTS The established method for determining 99 pesticides in Atractylodis Macrocephalae Rhizoma meets the methodological requirements. A total of 12 pesticides were detected in 53 batches of Atractylodis Macrocephalae Rhizoma samples, including: tebuconazole, benzofenapyr, cypermethrin and S-cypermethrin, pyraclostrobin, thiamethoxam, enoxymorpholine, diazinon, propiconazole, fipronil, and methoxam. According to the GB2763 conversion guidelines, the limit standard for diazinon in Atractylodis Macrocephalae Rhizoma was converted into a drug standard. CONCLUSION This study helps to understand the risk of pesticide residues in Atractylodis Macrocephalae Rhizoma and provides ideas for the formulation of pesticide residue limit standards for traditional Chinese medicine.

Diabetic peripheral neuropathy is one of the most common complications of diabetes. Aldose reductase is a key enzyme in the pathogenesis of diabetic complications. This review systematically reviews the efficacy and safety of five kinds of aldose reductase inhibitors in the treatment of diabetic peripheral nerves. Epalrestat is the only aldose reductase inhibitor in clinical application so far. A number of clinical trials have shown that epalrestat has a certain therapeutic effect on diabetic peripheral neuropathy and has sufficient safety, but long-term studies have shown that its therapeutic effect is not better than mecobalamine. Torrestat, zoporestat, ponastat, and fedastat were all withheld from the market or withdrawn from the market due to efficacy or safety concerns, which was inferred to be related to the structural characteristics of the drugs. Development of more effective and safer aldose reductase inhibitors from the perspective of drug structure will become one of the future research focuses on diabetic peripheral neuropathy.

OBJECTIVE To study the relationship between the spectral effect and the antibacterial effect of Rhizoma macrophylla L. based on grey correlation degree method and partial least square method. METHODS HPLC was used to establish the fingerprint of 13 batches of Moghania macrophylla (Willd.) Kuntze. The antibacterial activity of Moghania macrophylla (Willd.) Kuntze against 4 common pathogenic bacteria (Staphylococcus epidermidis, Escherichia coli, Staphylococcus aureus and Bacillus subtilis) was determined by microdilution method. Using the Similarity Evaluation System of Fingerprint of Traditional Chinese Medicine (TCM), the characteristic maps of 13 batches of Moghania macrophylla (Willd.) Kuntze were established, and the similarity evaluation and characteristic peak identification were carried out. The relative inhibition rate was used as the index of antibacterial activity, and the spectral effect relationship was established by using grey correlation analysis and partial least square method. RESULTS There were 29 common peaks in the fingerprints of 13 batches of samples, and the similarity was no less than 0.906. Peaks 12, 16, 17, 19 and 20 were identified as genistein, ononin, daidzein, genistein and chickpeas A. Staphylococcus epidermidis, Escherichia coli and Staphylococcus aureus had good bacteriostatic effect on 4 kinds of pathogenic bacteria. The results of spectral effect relationship analysis showed that peak 16 (ononin), peak 20 (chickpea A), peak 21 and peak 25 were the main active components of the antibacterial activity. CONCLUSION Through the study of the spectrum effect relationship, it is confirmed that the antibacterial effect of Moghania macrophylla (Willd.) Kuntze is the result of the combined action of many components, which could provide reference for the basic research and quality control of pharmacodynamic substances of Moghania macrophylla (Willd.) Kuntze.

OBJECTIVE To screen the effective components and potent substances of Bletilla striata and to preliminarily predict its mechanism of action. METHODS Oxford cup and microdilution methods were used to evaluate the inhibition of Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus in different extracted parts of Bletilla striata. Subsequently, a mouse model of acne vulgaris was established to assess the effects of the different extracted components of Bletilla striata on auricular tissue lesions, histopathology, and inflammatory factors. Furthermore, the chemical compositions of the three extracts were analyzed using ultra high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology was utilized to predict the relevant targets, pharmacodynamic components, and related pathways of Bletilla Striata in the treatment of acne. Additionally, molecular docking was performed on the key pharmacodynamic components and targets to further validate these pharmacodynamic substances. RESULTS The ethyl acetate extract of Bletilla striata could effectively inhibit three kinds of acne-causing bacteria, and its MIC was 2.34, 2.34, 4.59 mg·mL^-1, respectively, the ethyl acetate extract of Bletilla striata significantly improved the auricular tissue lesions in mice, while the remaining two extracts exhibited no anti-acne effect. A total of 51 components of Bletilla striata were identified, including 48 components in the ethyl acetate extract, 13 components in the butanol extract, and 15 components in the water extract, stilbenes were most enriched in the ethyl acetate extract. The results of network pharmacology and molecular docking validation indicated that constituents such as batatasin Ⅲ, 3-(4-hydroxybenzyl)-4-methoxy-2, 7-dihydroxy-9, 10-dihydrophenanthreneand, 3-O-methylbatatasin Ⅲ may serve as key active constituents of Bletilla striata in the treatment of acne. Additionally, MAPK1 and TNF among others may represent potential targets of Bletilla striata in anti-acne therapy. CONCLUSION This study shows that the ethyl acetate extracted parts of Bletilla striata have good anti-acne effects, in which the Stilbenes represented by batatasin Ⅲ may be the main medicinal components, which may provide important references for the in-depth study of the mechanism of Bletilla striata in treating acne.

OBJECTIVE To investigate the biosynthetic pathway of C₂₁ steroidal compounds in Cynanchum otophyllum Schneid. METHODS Metabolomics and transcriptomics were used to compare and analyze the relative contents of C₂₁ steroids in the roots, stems and leaves of C. otophyllum. Then, the genes related to C₂₁ steroid biosynthesis in C. otophyllum were screened through Kyoto Encyclopedia of Genes and Genomes(KEGG) database annotation. Finally, some differentially expressed genes (DEGs) were verified by quantitative real-time PCR. RESULTS The qingyangshengenin content in the roots was significantly up-regulated, with the relative qingyangshengenin content in the roots being approximately 73.10 times higher than that in the leaves and 19.05 times higher than that in the stems. Transcriptomic analysis revealed that 269 DEGs annotated C₂₁ steroidal biosynthetic pathways. By analyzing the DEGs annotated between the comparison groups, 18 key enzymes were screened out in the C₂₁ steroidal synthesis pathway, which were encoded by 87 genes, among which AACT and other enzymes were the key enzymes in the upstream stage of the biosynthesis pathway. Quantitative real-time PCR was performed to verify the expression trend of eight DEGs, which was consistent with the corresponding transcriptome data. CONCLUSION The biosynthetic pathway of C₂₁ steroidal compounds is systematically analyzed in this study, and several key enzymes and coding genes are screened, which enrich the omics data of C. otophyllum. These findings lay a foundation for further study on the biosynthesis mechanism of C₂₁ steroid compounds of C. otophyllum.

OBJECTIVE To prepare berberine hydrochloride microemulsion gel patch to improve the in vitro transdermal penetration and relative bioavailability in vivo. METHODS Firstly, through the screening of microemulsion dressing materials, and using the central point design response surface optimization method to optimize the microemulsion prescription, the best microemulsion prescription was obtained. The morphology and particle size of microemulsion were investigated by laser particle size analyzer and transmission electron microscope. Secondly, the matrix was selected for the gel paste, and then the optimal design of the gel paste was obtained by using the star design response surface optimization method. Finally, the microemulsion was added to the gel paste to prepare the berberine hydrochloride microemulsion gel paste, and the prescription process was verified. Through the in vitro transdermal test of mice, by comparing the permeation promoting effect of different concentrations of zzone, draw the cumulative permeation amount time curve of azone with different concentrations, and select the best amount of Azone. Finally, pharmacokinetic studies in rats and pharmacodynamic studies in mice were conducted. RESULTS Berberine hydrochloride microemulsion gel paste was successfully prepared. The best formulation of microemulsion was oil phase-emulsifier-co-emulsifier=0.11∶0.6∶0.3. The morphology and particle size of microemulsion were investigated by laser particle size analyzer and transmission electron microscope. The results showed that most microemulsion morphology was round, regular spherical, no aggregation, and the particle size was appropriate. The best prescription of gel paste NP700∶glycerol-dihydroxyaluminum aminoacetate=2.3∶17.5∶0.1 aluminum glycinate. The results of in vitro skin penetration test showed that azone with a mass fraction of 3% had the best penetration promoting effect. Pharmacokinetics showed that berberine hydrochloride microemulsion gel patch could prolong the action time in vivo. Preliminary pharmacodynamics shows that the drug can effectively improve the skin lesions, obviously inhibit the increase of inflammatory factors and improve the pathological tissue. CONCLUSION Microemulsion combined with gel patches can be used to prepare microemulsion gel patch with high drug loading and good therapeutic effect. The preparation of berberine hydrochloride microemulsion gel patch can effectively improve the bioavailability of berberine hydrochloride through percutaneous absorption.

OBJECTIVE To discuss the problems needing attention in the pharmaceutical research of oral soluble film generic drugs, and to provide reference for the research and development of oral soluble film generic drugs. METHODS By searching the relevant foreign review reports and literature, this paper comparatively analyzed the prescription technology of ondansetron oral soluble film listed in different regions, and combined with the relevant guiding principles, discussed the general considerations in the development of oral soluble film. RESULTS The main research contents of ondansetron oral soluble film were determined around the concerns of prescription technology, quality control and stability. CONCLUSION In the development of oral soluble film generic drugs, clinical drug demand should be taken into consideration,combined with the characteristics of raw and auxiliary materials, prescription composition and production process,reasonable inspection items should be rationally established,and conducting in-depth pharmaceutical research to improve the quality of oral soluble film generic drugs.

OBJECTIVE To develop appropriate formulation and process design for hot melt extrusion (HME) of poorly soluble drug posaconazole with aid of rheology and discriminatory dissolution. METHODS The viscoelastic properties of polymer matrices were assessed for oscillation shear strain on a rotation disc rheometer within temperature of 14-180 ℃ and angular frequency of 100-0.1 rads·s^-1, respectively. A paddle method and an open flow cell method were developed alternatively to screen key critical quality attributes. RESULTS The selected polymer carrier showed storage modulus (G') >loss modulus (G″) with loss factor Tan(delta) <1 within the assessed temperature range, for better HME processability. Oscillation-frequency assessments further demonstrated that G'and G″ were more shear stable with angular strain at 140 ℃ compared with the increasing modulus trends at 150 and 160 ℃. Based on quality by design, discriminatory dissolution helped in defining if need to add excipient hydroxypropylcellulose in the process, as well as in designing HME granule size for formulation drug T. DSC, XRPD, Raman and optical microscopy characterization showed that the morphology of API changed from multicrystalline state to amorphous molecule dispersion after extrusion. CONCLUSION The drug release in vitro and in vivo of formulation drug posaconazole T is in bioequivalence with that of reference listing drug.

OBJECTIVE To study the changes of main components of Angelica sinensis(A.sinensis) after stir-frying high performance liquid chromatography(HPLC) fingerprint combined with chemometrics. METHODS The HPLC fingerprints of A. sinensis before and after stir-frying were established. The fingerprints were analyzed and evaluated by similarity evaluation,principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA).The variable importance in the projection(VIP)value> 1 was used as the standard to screen the different components before and after stir-frying of A. sinensis,and paired t-test was performed on the different components. RESULTS There were 20 common peaks in the fingerprints of raw A. sinensis(RAS)and stir-fried A. sinensis(SFAS). After comparison with mixed reference substances, eight chromatographic peaks were identified as tryptophan, chlorogenic acid, ferulic acid, senkyunolide I, senkyunolide H, coniferyl ferulate, ligustilide, and butyliden phthalide.PCA(SFAS)showed that there were specific regions in the spatial distribution of principal components in the samples of RAS and SFAS. OPLS-DA screened out three differential components of ligustilide,senkyunolide I and coniferyl ferulate with VIP value> 1 as the standard.The peak areas of ligustilide,senkyunolide I and coniferyl ferulate were significantly reduced by paired t test (P<0.001). Chemometric analysis could effectively distinguish RAS and SFAS. CONCLUSION The chemical composition of RAS changes to a certain extent after stir-frying with soil.The established HPLC fingerprint had high similarity and could not significantly distinguish between RAS and SFAS. When combining HPLC fingerprint with stoichiometric analysis PCA,OPLS-DA and differential component distribution t test, RAS and SFAS can be obviously distinguished,which provides a reference for studying the processing principle of SFAS as well as data support for subsequent studies on pharmacological effects before and after processing.