Objective: To compare the effects of different extraction methods on polysaccharides from Polygoni Multiflori Radix, and to explore the differences of polysaccharides from Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata using hot water extraction. Methods: Polysaccharides from Polygoni Multiflori Radix were extracted by hot water extraction, ultrasonic extraction and microwave extraction, respectively. The yield, total sugar content, protein content, weight-average molecular weight (M_w), monosaccharide composition and DPPH free radical scavenging ability of polysaccharides were studied and compared. Results:The results showed that the yield of polysaccharides from Polygoni Multiflori Radix by different extraction methods was as follows: microwave extraction (M-PMP) > hot water extraction (H-PMP) > ultrasonic extraction (U-PMP). The protein content of U-PMP was the highest, and the M_w was obviously different from other polysaccharides. The results of monosaccharide composition showed that the monosaccharide composition of polysaccharide from Polygoni Multiflori Radix by different extraction methods was the same, which is mainly composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose, with different molar ratio of monosaccharides. Conclusion:There are some differences in the polysaccharide components extracted by three methods, and the yield obtained from different extraction methods varied significantly, with the highest yield of M-PMP. Some differences were found in polysaccharides from raw and prepared Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata.

Objective: To mine the security alert signals of neratinib based on the FDA Adverse Event Reporting System (FAERS) database to provide a reference for the safety of clinical medication. Methods: The adverse drug event (ADE) signals data of neratinib from the FAERS database from the third quarter of 2017 to the third quarter of 2021 were collected. The data mining was performed using the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) in the proportional imbalance method. Results: A total of 1 362 ADE reports with neratinib as the primary suspected drug were collected, and 96 neratinib ADE signals were mined; 71 signals were obtained after excluding non-adverse drug reaction signals, involving 13 systems. Among them, a total of 48 new signals were not mentioned in the instructions, accumulating 12 systems. Gastrointestinal disorders ADE entries totaled 2 186 cases, generating 25 signals; new signals from investigations accounted for 85.71% of their total system signals. Daily dose was not an independent risk factor for the occurrence of gastrointestinal disorders and investigations ADE. Logistic regression results showed that a course of treatment ≤7 days was an independent risk factor for the occurrence of gastrointestinal disorders, with statistically significant results (P=0.008); compared to a course of treatment ≤7 days, a course of treatment 1 to 3 months was an independent risk factor for the occurrence of investigations ADE (OR=4.288, 95% CI of 1.342 to 13.703;P=0.014). Conclusion: No matter what daily dose is used, adverse reactions need to be paid attention to. The duration of medication is of great significance to the risk of adverse reactions of neratinib, and pharmaceutical care should be strengthened during clinical medication.

Objective: To analyze the related substances produced in new production process of somatostatin, and the stability of raw materials and preparation was studied. Methods: The related substances were separated, collected, characterized and analyzed by high performance liquid chromatography, preparative liquid chromatography and ultra performance liquid chromatography-time-of-flight mass spectrometry tandem system. In addition, the stability of somatostatin and its preparation was studied under high temperature, light, oxidation and acidolysis destruction conditions. Conclusion: Based on the stability study combined with the production process of somatostatin and its preparation, somatostatin will produce new impurities in the new production process. This study provides a basis for revising pharmacopoeia standards.

Objective: To develop the determination method of the contents of 3′-hydroxy puerarin, puerarin, puerarin apioside, narirutin, naringin, hesperidin, neohesperidin, and praeruptorin A in Shensu Ganmao tablets (SGT) using high performance liquid chromatography with two-reference multi-component method (TRMC). Methods: The analyses were performed on an Agilent ZORBAX SB-C₁₈ column (250 mm×4.6 mm, 5 μm) using the mobile phase of 0.1% phosphoric acid-acetonitrile in gradient elution mode at a flow rate of 1.0 mL·min^-1. The detection wavelength was 283 nm. Results: Taking puerarin as internal reference, the RCF of 3′-hydroxy puerarin and puerarin apioside are 0.853 and 1.354. Taking naringin as internal reference, the relative correlation factors (RCF) of narirutin, hesperidin, neohesperidin, and praeruptorin A are 1.181, 1.027, 1.002, and 2.188. The RCF showed validated on different experimental conditions. The results of 8 components in SGT were in acceptable limits by using TRMC and the external standard method (ESM). Conclusion: The newly established TRMC can determine the characteristic constituents in Puerariae Lobatae Radix, Citri Reticulatae Pericarpium, Aurantii Fructus, and Peucedani Radix in SGT simultaneously, which can be used for quality control of SGT.

Bcr-Abl inhibitors are targeted drugs for the treatment of chronic myeloid leukemia (CML). Due to the high selectivity with few side effects, some of them have become the first-line drugs in the treatment of CML. Therefore, Bcr-Abl inhibitors have become the hotspot of anti-CML drug research. Based on the patent publication records of Bcr-Abl inhibitors, this article analyzes the research and development trends of Bcr-Abl inhibitors from the publication time and regional distribution, compares and analyzes the research progress through technical topics, and finally selects an enterprise to analyze its subsequent patent application for drug research and development in China and abroad, in order to provide relevant reference for the research and development of Bcr-Abl inhibitors.

Nanotechnology has greatly promoted the research and development of nanodrugs and nanoparticles, providing new therapeutic options for many diseases. However, due to their special physical and chemical properties and its easy accumulation in the liver, nanodrugs and nanoparticles can also bring potential hepatotoxicity risks to the body. This review summarizes the research progress of hepatotoxicity induced by nanodrugs or nanoparticles in recent years from the following three aspects: liver accumulation and cell-nanodrug interaction, toxic mechanisms and influencing factors of toxicity. Also, we discuss the limitations of the previous studies. This paper aims to provide new insights and references for the related researches on hepatotoxicity and preclinical safety evaluation of nanodrugs and nanoparticles.

Based on the characteristics of monoclonal antibody, this paper discusses the key points in the pharmacology and toxicology review of monoclonal antibody combined with our review practice and the technical guidelines issued by regulatory agencies. Recommendations are given on the quality of test substance, selection of related animal species, evaluation of immunogenicity and immunotoxicity, and selection of initial dose for the first human clinical trial, so as to provide general principles for designing scientifically acceptable non-clinical research programs for the sponsors and researchers.

Objective: To summarize the evaluation of meta analyses on the correlation between short-term endpoints (ORR, CR, etc.) and final endpoints (PFS, OS) in cancer, and to explore the correlation between different types of cancer. Methods: Based on Cooper et al. (2020), a systematic search in databases of Medline, Embase, the Cochrane library, Web of Science, and CINAHL were updated from March 2019 to January 2022. Meta analyses assessing the individual-level and trial-level correlation between short-term intermediate endpoints and final endpoints are summarized, and subgroup analyses are conducted in terms of the three most common cancer types. Results: The systematic review includes 77 studies across 20 types of cancer, in which non small cell lung cancer (NSCLC), colorectal cancer (CRC), and breast cancer are the three most common cancer types. The included studies mainly analyzed the correlation between ORR and OS (91%) or PFS (35%), and the correlation was week regardless of individual-level and trial-level. In subgroup analyses, over half studies in NSCLC indicated good or excellent trial-level correlation between ORR and PFS (R²>0.4). Also, most studies in NSCLC and CRC indicated that the trial-level correlation between ORR and PFS >0.3, >0.2) was stronger than that between ORR and OS (>0.1, >0.1). Conclusion: The short-term intermediate endpoints, such as ORR, may not be good surrogates for final endpoints. ORR may be a short-term intermediate indicator worth be noticed by regulators, which could be surrogate for PFS in trial-level in the field of NSCLC and CRC, especially in the field of NSCLC.

3CL protease inhibitors has become the focus of the current research on anti-coronavirus drugs. The analysis of the patent information will help the research and innovation of such anti-coronavirus drugs. This paper analyzes the application trends of anti-coronavirus 3CL protease inhibitor-related patents, the distribution of regional status of patents, important applicants, patented technology themes, progress of key drug development and other factors. We also analyze the development of related patent technologies and aim to help domestic pharmaceutical enterprises carry out innovation and complete the strategic layout.

Pituitrin, oxytocin and vasopressin, as the drugs related to the posterior pituitary, play an irreplaceable role in clinic. Based on the relevant research results of our laboratory and literature survey, this paper analyzes the research status of quality standard of pituitary hormone-related drugs, and further puts forward revision suggestions, in order to provide reference for the improvement of drug quality standard and ensure the safety of clinical medication.