OBJECTIVE To establish the fingerprints of 50 batches of Arnebiae Radix and the methods for determination of the contents of six components. METHODS A high performance liquid chromatographic (HPLC) method was used for the determination of 50 batches of Arnebiae Radix on an Agilent 5 TC-C₁₈(2) column, with acetonitrile-0.05% formic acid aqueous solution as the mobile phase, gradient elution at a flow rate of 1 mL·min^-1, detection wavelength of 275 nm, and column temperature of 30 ℃. The contents of six naphthoquinone components, i.e., alkannin, acetylshikonin, deoxyshikonin, β-acetoxyisovalerylshikonin, isobutyryl alkannin, and β,β'-dimethylacrylalkannin were determined. The fingerprints of the herbs were established by HPLC fingerprinting combined with the “Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System (Version 2012A)” to evaluate the similarity and confirm the common peaks. RESULTS The methodological validation results showed that the peak areas of the six components had good linear relationships in the corresponding concentration ranges, and the contents of the six components ranged from 0.006%-0.237%, 0.009%-1.759%, 0.001%-0.129%, 0.002%-0.625%, 0.011%-0.609%, and 0.016%-1.712%, respectively. The HPLC fingerprints of Arnebiae Radix were established, and a total of nine common peaks were calibrated. The similarity fitting was performed by using the TCM fingerprinting software, and it was found that the similarity of the 50 batches of Arnebiae Radix varied greatly. CONCLUSION The HPLC fingerprint of Arnebiae Radix established in this study and the method of simultaneous determination of the contents of six components are simple, stable, accurate, reliable, and reproducible, which can provide a basis for the quality study of Arnebiae Radix.

OBJECTIVE To establish UPLC fingerprint of Angelica dahurica cv. Qibaizhi, identify the compounds of common peaks by UPLC-Q-TOF-MS technology, determine antioxidant activity of each batch and study the relationship between effects of antioxidant and spectrum of Angelica dahurica cv.Qibaizhi. METHODS The fingerprint of 28 batches of Angelica dahurica cv. Qibaizhi was established by the Similarity Evaluation System of TCM Chromatographic Fingerprint (2012 edition), and the common peaks were identified and evaluated for similarity, and the common peaks were analyzed by UPLC-Q-TOF-MS. The free radical scavenging rate of 1, 1-diphenyl-2-trinitrophenylhydrazine (DPPH) was used as antioxidant index to determine its antioxidant activity. Grey correlation degree and partial least squares regression were used to analyze the spectral effect relationship between chemical constituents and antioxidant activities of Angelica dahurica cv. Qibaizhi. RESULTS The fingerprints of 28 batches of Radix Angelica were established, the similarity was 0.910-0.997. By cluster analysis, the different processing methods can be divided into two categories: sulfur fumigation and sulphur-free. When the square Euclidean distance is 10, the sulphur-free Angelica dahurica cv. Qibaizhi can be further divided into two categories, which is consistent with the classification of commodity specifications. A total of 13 common peaks were identified. The common peaks were identified by comparison of standards and UPLC-Q-TOF-MS analysis as quinic acid, dihydrooroselol, oxypeucedanin hydrate, byakangelicin, xanthotoxin, bergapten, isopimpinellin, oxypeucedanin, imperatorin, phellopterin, cnidilin, isoimperatorin and falcarinolone. By scavenging DPPH free radicals, it was found that 28 batches of Angelica dahurica cv. Qibaizhi had antioxidant capacity. The spectral analysis results showed that the antioxidant capacity was positively related to quinic acid, bergapten, oxypeucedanin, phellopterin, isoimperatorin and falcarinolone. CONCLUSION In this study, a quality evaluation model of Angelica dahurica cv. Qibaizhi based on chemical composition and activity is established, which provides a reference for elucidating the antioxidant active ingredients and quality control in Angelica dahurica cv.Qibaizhi.

OBJECTIVE To investigate the impact of polyethylene oxide (PEO, POLYOX^TM), penetration additives, and butylated hydroxytoluene (BHT) on tablet properties and drug release of mirabegron extended release (ER) tablets and provide some ideas of formulating polyethylene oxide based ER tablets for the formulators. METHODS Single-factor-experiment was applied to investigate the impact of formulation components on drug release of mirabegron ER tablets. Different molecular weight (MW), series of particle size and use level of polyethylene oxide, three types of penetration additives (PEG 8000, PEG 4000 and lactose) and several use levels of butylated hydroxytoluene (BHT) were investigated. RESULTS Mirabegron ER tablets formulated with polyethylene oxide WSR N60K at 28% use level got statistically equivalent drug release with marketed mirabegron ER tablets. Higher MW and higher use level of polyethylene oxide led to slower drug release, while lower MW and lower use level led to faster drug release. Particle size of polyethylene oxide WSR N60K did not significantly affect mirabegron drug release. The tablets using either polyethylene glycol (PEG 8000 or 4000) or lactose as penetration additives could achieve equivalent drug release as marketed mirabegron ER tablets. The blend of polyethylene oxide WSR 301 and N12K at ratio of 35∶65 has the same viscosity with polyethylene oxide WSR N60K and led to statistically similar drug release. CONCLUSION Formulation of polyethylene oxide based mirabegron ER tablets are robust.

OBJECTIVE To systematically study the micro-characteristics and microscopic characteristics of 9 commercially available Epimedium leaves, summarize more exclusive and practical features and provide reference for effective identification of Epimedii Folium on market. METHODS Using the character identification, micro-character identification, microscopic identification and combining with the technique of depth synthesis, high definition feature images of 9 species of Epimedium leaves were obtained. Some of the feature maps were extracted digitally and analyzed by SPSS 26.0 software. RESULTS The micro-characteristics of petiole hair, leaf margin spines, nipple and hairs on lower surface, parenchyma number on the base of leaf main vein transverse section, cuticle on the surface of leaf, as well as the microscopical characters of upper epidermal cell wave depth, non-glandular hair and nipple surface morphology, all of that can be regarded as specific features of 9 species of Epimedium leaves in classification and identification. There was statistically significant difference in the angle of thorns at the edge of leaves, the proportion of wave depth in upper epidermal cells and the density of nipple among all samples (P<0.05). CONCLUSION Nine kinds of Epimedium leaves could be distinguished through the micro-characteristics and micro-identification methods. The quantitative analysis and statistical analysis of micro-property will make up for the deficiency of traditional experience identification by subjective factors. The results of this study will provide a reference for the circulation, inspection, clinical medication and standard drafting and so on.

OBJECTIVE To discuss the rationality of the current methods for examining viable bacterial count and contaminating bacteria in the standard of Bacillus cereus tablets, and optimize the two methods. METHODS The factors that affect the method for viable bacterial count were compared and analyzed, such as medium, diluent, dilution ratio, and pre-treatment, then the optimal experimental conditions were selected. The microbial limit test in the current standard was replaced with the contaminating bacteria test under the general chapter for probiotic in Chinese Pharmacopoeia part III, and its suitability was studied. RESULTS The optimized method for determination of viable bacterial count could more effectively recover Bacillus cereus in the sample, and the results were significantly higher than the current standard method. The use of a new method for detecting non-pathogenic bacteria can discover potential risks in the sample, and its suitability investigation results basically met the requirements of the Chinese Pharmacopoeia. CONCLUSION The new methods are suitable for the determination of viable bacterial count and detection of contaminating bacteria in Bacillus cereus tablets. The current standards for the determination of viable bacterial count and microbial limit testing cannot effectively monitor product quality risks. It is recommended to revise the methods. This can not only more effectively regulate products, but also better assist manufacturers in improving product quality.

OBJECTIVE To prepare tetrahydropalmatine gel emulsion with Bletilla striata polysaccharide, and investigate its stability and dissolution characteristics in vitro. METHODS The nascent soap method combined with high pressure homogenization method were used to prepare tetrahydropalmatine gel emulsion. Using the particle size and polydispersity index (PDI) as evaluation indexes, the single factor response surface method was used to screen the optimal prescription, and the biological properties of tetrahydropalmatine gel emulsion were investigated. RESULTS The optimum formula was m(Bletilla striata polysaccharide)-m(konjac gum)=50∶1, triethanolamine mass fraction of 0.8%, stearic acid mass fraction of 2.0%. The gel emulsion of tetrahydropalmatine was milky white, fine, uniform and glossy, and had good moisturizing, coating and stability properties. The average particle size and PDI value were about (1.56±0.04) μm, (0.434±0.03), and the cumulative transmittance of the gel emulsion for 24 h was (915.23±85.55) μg·cm^-2. CONCLUSION The tetrahydropalmatine gel emulsion prepared in this experiment has good appearance, moisture retention, coating and stability, and good transdermal absorption rate. The research results can provide reference for the further development and utilization of tetrahydropalmatine.

OBJECTIVE To prepare a “sandwich” oral film (composed ofthe backing layer, sustained release layer, and adhesion layer) containing triamcinolone acetonide for the treatment of oral ulcers. METHODS Triamcinolone acetonide oral film was prepared by a tape casting process using ethyl cellulose (EC), hydroxypropyl methylcellulose (HPMC), and polyacrylic acid (PAA) as carrier materials. Taking the appearance, thickness, uniformity, adhesion, and mechanical strength of the film as indicators, the formulation of the backing layer, sustained release layer, and adhesion layer was optimized by a single factor study. The film's physicochemical properties and drug release in vitro were compared with the commercially available formulation Taisho^®. RESULTS The drug loading of the resulting triamcinolone acetonide three-layer oral film was 96.0%, and the film had good uniformity, mechanical strength, and adhesion. The designed oral film had a release curve similarity factor f₂ of 54.25 when compared to the commercially available formulation of Taisho^®. CONCLUSION The quality of triamcinolone acetonide oral film prepared by the tape casting process is consistent with that of Taisho^®. Moreover, the technology of this film is simple and feasible, with the potential for industrial conversion.

OBJECTIVE To analyze the chemical components of Longzuan Tongbi Granules, a classical prescription of Zhuang medicine by liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS The MS/MS data were collected in positive and negative ion mode after gradient elution of the test solution using an ACQUITY UPLC HSS T3 column (2.1 mm×100 mm, 1.8 μm) and a mobile phase system consisting of 0.1% formic acid water (A)-0.1% formic acid acetonitrile (B). RESULTS A total of 113 compounds, including 64 alkaloids, 20 flavonoids, 12 organic acids, 8 coumarins, 5 lignans and 4 others, were identified by high-resolution mass spectrometry data analysis, reference substance and database comparison, while referring to the mass fragmentation patterns of relevant components reported in the literature, and of which 109 secondary metabolites were attributed for recognition. CONCLUSION The material basis of Longzuan Tongbi Granules is rich, represented by alkaloids, and Toddalia asiatica is the important “main drug”. This information can provide a scientific basis for the pharmacodynamic mechanism study and rational clinical use of this formula.

OBJECTIVE To establish a high performance liquid chromatography-refractive index detector method for the determination of main potential carbohydrate residues fructose and sucrose concentration in dextran 40 raw materials from different of production processes, analyze the differences in carbohydrate residues in dextran 40 produced by different manufactures, and provide a reference for the quality evaluation of related drugs and the formulation or edit of national drug standards. METHODS Isocratic elution was performed on a ZORBAX-NH₂ column. Mobile phase consisted of 75% acetonitrile and 25% water at a flow rate of 1.0 mL·min^-1. RID was used as detector. The detector temperature and column temperature was maintained at 40 ℃ and the injection volume was 50 μL. RESULTS Sucrose was not detected in all batches of dextran 40. Fructose residue could only be detected in dextran 40 which using alcohol precipitation production process, and the content was 0.005%-0.14%. No fructose residue was detected in the dextran 40 of manufacturer B using membrane filtration method. CONCLUSION The HPLC-RID method is established to determine the content of fructose and sucrose in dextran 40. The method has strong specificity, high sensitivity, good stability and simple operation. The amount of fructose residual in dextran 40 produced by different processes varies greatly. The fructose residual in the raw material of dextran 40 obtained by membrane filtration is significantly lower than that by alcohol precipitation, it is necessary to control the fructose residue in the quality standard.

Central nervous system (CNS) diseases are a serious threat to human health. However, due to the existence of blood-brain barrier (BBB), there is a lack of effective technology to deliver drugs to the brain, which seriously affects the success rate of drug development related to CNS diseases, resulting in treatment results that are often unsatisfactory. Therefore, a new technology is urgently needed to solve the above problems. Brain targeted peptide-drug conjugates, which consist of a brain targeted peptide, a linker, and a payload, have become a promising CNS drug by enabling bioactive molecules to cross the BBB and reach the brain parenchyma by using biologically relevant endogenous transport mechanisms. In this review, the types and characteristics of brain targeting peptides, linkers, and payloads are briefly introduced, and some common brain targeting peptide-drug conjugates are listed, as well as the challenges faced by such drugs and the improvement methods, in order to provide ideas for the design and development of drugs for CNS diseases.