OBJECTIVE To examine the herbal evidence of “Agaru” Tibetan medicines,conduct biopharcological studies and proveide a basis for the corrent origin and quality control. METHODS Through literature research, combined with field visits and expert consultations, variety classification, origins, characteristics and effects, compound preparation,and quality standards of “Agaru” type Tibetan medicines were compiled and summarized. The morphological and microscopic characteristics of “Aerma” medicinal materials were observed. Physicochemical identification was carried out based on thin-layer chromatography and determination of volatile oil components and content using GC-MS technology. RESULTS The name “Agaru” has evolved from Sanskrit loanwords and is a typical Tibetan medicine characterized by “multiple varieties and multiple origins”. Tibetan medicine often classifies it based on color into three categories: white (transliterated as “A Er Jia” or “A Jia Ga Bu”), black (transliterated as “A Er Na” or “A Ga Na Bao”), and red (transliterated as “A Er Ma” or “A Ga Ku Ao”). There is a significant difference in the varieties and origins of “Agaru” type Tibetan medicines used by Tibetan doctors in different regions, involving about 15 species (including varieties and forms) of plants from 5 families and 7 genera. Among them, “Alma” is widely used clinically, and its mainstream base is the heartwood of Camphora glandulifera (Wall.) Nees. Biopharmacological research was carried out on “Aerma” [C. glandulifera (Wall.) Nees], a clinically used variety of the “Agaru” group of Tibetan medicines, providing basic data for the establishment of its quality standards. CONCLUSION This study completes the botanical verification of the Tibetan medicine “Agaru” and the pharmacognostical research on “Aerma” [C. glandulifera (Wall.) Nees]. This will provide an important basis for the scientific evaluation of quality and in-depth development of “Agaru”.

OBJECTIVE To investigate the clinical efficacy of aspirin combined with Huoxue Quyu decoction in the treatment of lower extremity arteriosclerosis obliterans (ASO). METHODS A total of 136 patients with lower extremity ASO admitted to our hospital were selected as the research objects, aged 49-87 years, with an average age of (65.00±6.54) years. According to treatment methods, 68 cases of conventional aspirin treatment were included in the control group, and 68 cases of Huoxue Quyu prescription combined with aspirin were included in the study group. The platelet function, hemodynamic index, blood lipid index, arteriosclerosis index, health status and clinical effect of the two groups were compared before and after treatment. Generalized estimation equation (GEE) model was used to analyze the factors affecting the clinical efficacy of ASO in the lower extremities, and GEE model was used to analyze the interaction effects of ankle-brachial index(ABI) at different time points, different groups and different stages. RESULTS After 6 weeks of treatment, the platelet function, hemodynamic indexes, lipid indexes and arteriosclerosis indexes of the two groups were significantly different compared with those before treatment (P<0.05). PAR, D-D, FIB, HWBV, LWBV, ESR, TC, TG and LDL-C levels in the study group were significantly lower than those in the control group (P<0.05), while BT, HDL-C, ABI, TBI, lameness distance, health status score and clinical efficacy were significantly higher than those in the control group (P<0.05). GEE model analysis showed that treatment method, treatment time and Fontaine stage significantly affected the therapeutic effect of ASO in lower limbs (P<0.05). In the interaction effect analysis, after 2 and 4 weeks of treatment, the ABI values of ASO patients in the study group and the control group were significantly different (P<0.05). After 6 weeks of treatment, different treatment methods had statistically significant effects on ABI values of ASO patients in stage Ⅱ, Ⅲ and Ⅳ (P<0.05). CONCLUSION Aspirin combined with Huoxue Quyu decoction is better than aspirin alone in the treatment of lower extremity ASO in the aspect of improvement of platelet function, hemodynamics, blood lipids and arteriosclerosis. After 6 weeks of treatment, the total effective rate and health status SF-36 score of the study group with combined medication are significantly higher than those of the control group. Treatment method, treatment time and Fontaine stage significantly affect the therapeutic effect of lower extremity ASO.

OBJECTIVE To evaluate the safety characteristics of Rehmannia glutinosa leaf total glycosides capsules in juvenile Wistar rats, and provide reference for the use of Rehmannia glutinosa leaf total glycosides capsules in child and adolescent patients. METHODS Twenty-seven-day-old Wistar rats were randomly divided into control and low-, medium-, and high-dosage groups. Each dosage group was given the Rehmannia glutinosa leaf total glycosides by gavage repeatedly for 8 weeks, followed by a 4 week recovery. The clinical symptoms, body weight, food consumption, hematological and serum biochemical indexes, central nervous system function, learning and memory ability, skeletal development, reproductive function, organ weight and histopathological changes of the rats was observed. RESULTS Rehmannia glutinosa leaf total glycosides capsules did not show significant effects on the clinical symptoms, body weight, food consumption, hematological and serum biochemical indexes, main organ weights, central nervous system function, bones, sexual cycle, sperm counts, vitality and form of the rats. No histopathological changes were observed associated with Rehmannia glutinosa leaf total glycosides capsules. CONCLUSION The no-observed-adverse-effect-level (NOAEL) for Rehmannia glutinosa leaf total glycosides capsules in juvenile rats is determined to be 750 mg·kg^-1 in the 8 week feeding study. The data provides reference for the use of Rehmannia glutinosa leaf total glycosides capsules in child and adolescent patients.

OBJECTIVE To prepare methotrexate (MTX)-nicotinamide (NIC) coamorphous (MTX-NIC CA), evaluate its pharmacokinetic behavior in rats, and explore its solubilization mechanism. METHODS The coamorphous complex was prepared by melting method and characterized by powder X-ray diffraction and other techniques; the physical stability and thermodynamic stability of MTX-NIC CA were examined. The solubilization mechanism was studied by solubility profile method. The concentration of MTX in rat plasma was determined by high-performance liquid chromatography and the pharmacokinetic curve was drawn. RESULTS The physical stability of MTX-NIC CA was good; the reaction of MTX with NIC was a spontaneous enthalpy-driven reaction, and the mechanism of NIC for enhancing the solubility of MTX was that a soluble A_L-type complex with a ligand-to-metal ratio of 1∶1 was formed in solution. Compared with the raw drug MTX, the t_max of MTX-NIC CA was prolonged, and the c_max, AUC_0-t, AUC_0-∞ and F were significantly increased (P<0.05). CONCLUSION The MTX-NIC CA is successfully prepared by melting method with good stability, and the formation of co-amorphous complex improves the bioavailability of poorly soluble 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.

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 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 analyze the distribution frequency of rs2306283 and rs4149056 polymorphisms in the solute carrier organic anion transporter family 1B1(SLCO1B1) gene and investigate the effect of SLCO1B1 gene on the efficacy and safety of different moderate kinds of statins in patients with coronary heart disease(CHD). METHODS A total of 183 blood samples of patients with CHD were collected, and polymerase chain reaction-fluorescence probe technology was used to detect the polymorphism of SLCO1B1 gene. Blood lipid indicators and blood biochemical indexes before and after statin treatment (atorvastatin, rosuvastatin, other statins), such as triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), and urea nitrogen(BUN), serum creatinine(Scr), creatine kinase(CK), alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), direct bilirubin(DBIL), indirect bilirubin(IBIL), et al, were recorded. The change values of TG, TC, LDL-C, HDL-C, et al, were calculated. The relationships between SLCO1B1 gene polymorphism and the efficacy and safety of different statins in CHD patients were analyzed. RESULTS There was significant difference between Han and Uyghur CHD patients in the distribution frequency of SLCO1B1 A388G genotypes. The difference in LDL-C was significantly increased in SLCO1B1 388AG+GG patients compared with AA(P<0.05). The difference of LDL-C after treatment in 388AA type was significant(P>0.05), and the change of HDL-C in GG type patients treated with rosuvastatin was significantly higher than patients with atorvastatin(P<0.05). The changes of HDL-C in TT genotype patients with other statins were significantly higher than patients with atorvastatin(P<0.05), and the change values of TC and LDL-C in TT genotype patients with atorvastatin were significantly higher than those of the rosuvastatin group (all P<0.05). The ALP levels in SLCO1B1 388AG genotype patients with rosuvastatin were significantly lower than the other statins (P<0.05), and the DBIL levels in GG patients with other statins were significantly higher than the rosuvastatin and atorvastatin (P<0.05). The IBIL, CK levels and the change of ALT in SLCO1B1 521TC patients were higher than TT (all P<0.05). The AST increase in TT genotype patients with atorvastatin was significantly lower than that of other statins (P<0.05), and the IBIL levels in TC genotype patients with rosuvastatin and atorvastatin were significantly lower than the other statins (P<0.05). CONCLUSION There is relevance between SLCO1B1 rs2306283 and rs4149056 gene polymorphisms and efficacy and safety of different statins treatment. SLCO1B1 388G allele enhances the lipid-lowering effect of rosuvastatin, especially on HDL-C. SLCO1B1 521T allele enhances the lipid-lowering effect of atorvastatin, especially for LDL-C and TC, and the 521C allele may increase the risk of myopathy and liver function impairment. There is relevance among SLCO1B1 rs2306283 and rs4149056 gene polymorphisms and efficacy and safety of different statins treatment, which may be a genetic indicator to predict the efficacy and adverse effects of statins.

OBJECTIVE To investigate crystal structure and composition of synthetic and natural cinnaba,compare their spectroscopic characteristics and analyze their microscopic characteristics and trace element differences. METHODS This investigation endeavors to clarify the crystal configuration and phase composition of synthetic and natural cinnabar on the market and analyze the differences in trace elements between them. Meanwhile, we used powder X-ray diffraction, Raman spectroscopy, attenuated total reflection-Fourier transform infrared spectroscopy, electron probe micro-analysis, inductively coupled plasma mass spectrometry, with traditional microscopic identification(characteristics; optical polarized light microscopy), to explore the identification methods of synthetic and natural cinnabar. RESULTS The results suggest that, both present to share the same characteristics in the crystal forms of synthetic and natural cinnabar. Common impurities in natural cinnabar are quartz, pyrite, calcite, stibnite, etc., while the differences among different batches of samples are distinguishable. Synthetic cinnabar contains a small number of calcite impurities, and the quality is relatively uniform. By using electron probe micro-analysis technology, and powder crystal X-ray diffraction technology combined with polarized light microscopy, the impurities in synthetic cinnabar and natural cinnabar can be effectively analyzed and identified; the mid-infrared spectrum and Raman spectrum characteristics of synthetic and natural cinnabar are similar; the characteristic trace elements between synthetic and natural cinnabar are consistent. CONCLUSION Three elements including Fe, Mg and Zn can be quantified to identify these two as reference.