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 interpret Guidance on Quality Control for Nanomedicines (interim) issued by center for drug evaluation, NMPA, and provide reference for the development of nanomedicines. METHODS By conducting a systematic review of domestic and international literature and combining background of the guidance, this paper discussed the definition and classification of nanomedicines, quality research and control strategies, process control and stability research. It also proposes points of attention in the quality control studies of nanomedicines with cases. RESULTS and CONCLUSION The special nano-size, structure and surface properties of nanomedicines may significantly change the physicochemical properties and behaviors of active pharmaceutical ingredients in vitro and in vivo, which in turn affect their safety and efficacy. Quality research spans the entire lifecycle of nanomedicines. Critical quality attributes related to nano-characteristics should be evaluated based on the type, composition and structure of nanomedicines, manufacturing process, as well as their clinical use. Risk assessment strategy based on drug evaluation should focus on the impact of the quality attributes of nanomedicines on their safety and efficacy.

Skin, as the first line of defense of the body, is often damaged by various factors, causing skin trauma. Skin wound repair has become a serious health problem. Medical wet dressings can create a sustained moist environment around the wound, stimulating the release of cytokines and cell proliferation, as well as enhancing the function of inflammatory cells, which have broad prospects in promoting wound healing. With the advancement of medical technology, multifunctional wound treatment strategies and auxiliary treatment technologies combined with medical wet dressings have provided better treatment options for skin wound repair and healing. This article summarizes the types and applications of medical wet dressings, elucidates and generalizes the research progress on functional medical wet dressings and related auxiliary treatment technologies, providing insights for researchers to develop new types of medical wet dressings.

OBJECTIVE To evaluate and analyze real-world post-marketing adverse drug reactions(ADRs) of sindilizumab and provide critical reference for safe clinical medication. METHODS The data were sourced from the National Adverse Drug Reaction Monitoring System database, covering ADR reports related to sindilizumab in Beijing area in the past five years. These reports identified sindilizumab as the suspected drug to the ADRs. Statistical analysis was conducted using SPSS 22.0 software. RESULTS A total of 155 sindilizumab-related ADR reports were analyzed. In terms of gender distribution, the ratio of male to female patients was 1.77∶1. Skin reactions were the most common ADRs reported. Allergic reactions dominated ADR reports occurring within 24 hours. Severe ADRs accounted for 26.45% of the reports, with most severe reactions occurring after 24 hours of medication use (P=0.005). In patients with tumors not included in the approved indications, the risk of experiencing severe ADRs was significantly higher compared with those with indicated conditions (P=0.006). Nine patients experienced ADRs due to drug dosages exceeding the recommended dosage in the instructions. Additionally, the concomitant use of the drug with lenvatinib was associated with the emergence of new safety signals, including myocardial infarction and diabetic ketoacidosis, necessitating heightened vigilance in clinical practice. CONCLUSION This investigation has uncovered an augmented risk of severe ADRs in individuals receiving medications for non-indicated uses. Consequently, implementation of stricter surveillance measures is needed for patients with off-label conditions to facilitate timely medical interventions. Notably, a significant incidence of severe ADRs is observed to occur beyond the initial 24-hour period following treatment. Thus, individuals receiving the drug in day-care unit should be explicitly instructed to closely monitor their post-medication health status upon discharge and to seek immediate medical consultation in case of any arising discomfort. There exists noncompliance with the recommended dosage, thus attention should be paid to such cases. Moreover, concurrent use of sindilizumab with lenvatinib has been identified to induce myocardial infarction and diabetic ketoacidosis, representing a new safety signal that demands clinical caution.

Traditional Chinese medicine (TCM) decoction is a complex dispersion system, and its active components are mostly to form different phases in the form of solutes or dispersed substances, such as true solution, colloidal phase, suspension phase, etc. The active components are complex and diverse, and the formation, transformation, and transmission of each phase may affect the metabolism and action process of the pharmacodynamic components in biological bodies. However, the study on the phase differences and effective phases in TCM decoction is still in the initial stage. In this paper, we will be explored the quality basis and mechanism of TCM decoction from the perspectives of the formation, characterization, transformation, transmission and mechanism of the ordered phase in TCM decoction, and look forward to the quality research mode of TCM based on phase structure, so as to provide a reference for explaining the effect mechanism of TCM decoction from the perspective of structural TCM decoction.

OBJECTIVE To establish a callus culture system for dedifferentiation of Mahonia fortunei (Lindl.) in order to screen the key genes involved in the biosynthesis of jatrorrhizine. METHODS The contents of benzylisoquinoline alkaloids in callus at different dedifferentiation stages were determined by HPLC. Transcriptome was used to analyze the gene expression profiles of callus at different dedifferentiation processes and identify the differentially expressed genes. By analyzing the relationship between the variation of alkaloid content and the differentially expressed genes, the key genes involved in the biosynthesis of jatrorrhizine were screened. RESULTS The contents of columbamine, palmatine, jatrorrhizine and berberine increased in varying degrees during the dedifferentiation of Mahonia fortunei (Lindl.) leaves, among which jatrorrhizine increased significantly. By comparing and analyzing the transcripts of the leaves of Mahonia fortunei (Lindl.) and samples from different dedifferentiated stages, differential expression genes between different dedifferentiated stage samples were screened. Furthermore, through KEGG enrichment analysis, cluster analysis, 25 differentially expressed genes involved in jatrorrhizine biosynthesis pathway were annotated, among which NCS, 7OMT, CNMT, BBE, CAS, STOX may be potential key genes. CONCLUSION During the dedifferentiation period, the contents of columbamine, palmatine, jatrorrhizine and berberine all increase, among which the contents of jatrorrhizine increases the most significantly. Callus culture can be used as a method to produce benzyl isoquinoline alkaloids such as jatrorrhizine.

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 investigate the key factors and directions for construction of a standard system for microbial control of pharmaceutical excipients. METHODS The contents related to pharmaceutical excipient microbial control including general requirements and monographs of standards in Chinese Pharmacopeia, United States Pharmacopeia and European Pharmacopeia were extracted and analyzed in combination with the current industrial status. RESULTS The included pharmacopoeias exhibit considerable differences in the coverage of pharmaceutical excipients and requirement for microbial control and there is still a lack of scientific and systematic guiding standards. The industrial requirements are yet to be met in terms of testing methodology, standardization, and instruction. CONCLUSION Attention should be paid to the methodological research and risk management of microbial control of pharmaceutical excipients. Instructive standards for microbial control of pharmaceutical excipients should be developed based on comprehensive consideration of excipient features and intended use with formulation as a core, to improve the quality standard system of pharmaceutical excipients and ensure drug safety.

In recent years, National Medical Products Administration has successively issued special documents such as “Several Measures to Further Strengthen the Scientific Regulation of Traditional Chinese Medicine(TCM) and Promote the Inheritance, Innovation and Development of TCM”, “Special Regulations on Registration and Management of TCM” and “Special Regulations on the Management of TCM Standards”, which put forward new requirements for the research, formulation and management of TCM standards, and is of great significance for the comprehensive construction of a new system for the management of TCM standards, the establishment of the most rigorous TCM standards, and the promotion of high-quality development of TCM industry. Due to the natural source of TCM, the complex composition of drug components, the unique theoretical system and the safety and effectiveness derived from clinical practice, it is difficult to objectively evaluate and effectively control the quality of TCM preparations based on qualitative and quantitative quality control models based on chemical components and the quality standards established thereby. How to realize the advanced characterization and objective identification of TCM quality based on the characteristics of TCM, and to study and establish the corresponding quality standard of TCM preparation has become an important content of TCM quality research, the focus and difficulty of TCM supervision scientific research, and the bottleneck of TCM quality improvement and standard formulation. At present, the quality control of TCM preparations has established a whole process quality control system from TCM crude drugs, decoction pieces to preparations, and formed a quality standard system of TCM preparations based on the characteristics of TCM consisting of the standards of TCM crude drugs, decoction pieces, extracts and preparations. By sorting out the development history of TCM quality standards, this paper analyzs the problems and challenges in the research of TCM quality standards, and discusss the strategies and methods for the research of TCM preparation quality standards based on the characteristics of TCM in combination with the scientific research results of TCM regulatory science in recent years, and the actual research and development and review of TCM, so as to provide reference for colleagues in the industry.

Since the enactment of China's first “Drug Administration Law of the People's Republic of China” in 1984, China has entered a phase of legal and standardized drug management. The drug regulatory authorities have continuously strengthened the construction of the legal and regulatory framework for drug supervision and have optimized the drug review and approval system. The accessibility of drugs for rare diseases is a significant challenge worldwide. To meet the medication needs of patients with rare diseases, China has introduced a series of incentive policies to fully support the development of drugs for rare diseases and accelerate their review and approval. This paper systematically reviews the historical evolution, development process, and reform achievements of China's rare disease drug review and approval system, and looks ahead to the future, aiming to further optimize the system to better meet the medication needs of patients.