Based on the Innojoy patent database platform, this study conducts a comprehensive search and statistical analysis of patents related to major varieties of Chinese medicinal materials across 130 global patent agencies. The analysis included various aspects, such as geographic distribution, technical subject matter, applicants, and patent value. Analysis shows that the global research on major varieties of Chinese medicinal materials has shown a generally stable trend over the past five years. Patent applications are mainly concentrated in China, the United States, South Korea and Japan, among which the United States has the largest number of high-value patents and the strongest overall strength. In recent years, the number of patents applied by Chinese enterprises has surpassed that of countries such as the United States. The application trend remains relatively stable, and the distribution of applicants is quite concentrated. However, the number of high-value patents is still lacking, and the overall strength is relatively weak. Therefore, it is suggested that relevant enterprises and research and development organizations in the traditional Chinese medicine industry draw inspiration from the patent application strategies employed in U.S. By continuously improving the technological strength and competitiveness of the traditional Chinese medicine large variety industry, they can further promote in-depth development of research in major varieties of Chinese medicinal materials.  This can be achieved through strengthening innovative research and development efforts, as well as improving the quality and value of patent applications related to traditional Chinese medicine.

The U.S. Food and Drug Administration (FDA) has officially approved Cobenfy (xanomeline and trospium chloride) for the oral treatment of adult schizophrenia on September 26, 2024. Cobenfy is the first antipsychotic with a potentially novel pharmacological mechanism since the introduction of chlorpromazine in 1952 and is the first completely new drug in decades to receive FDA approval for the treatment of schizophrenia. In completed clinical trials, Cobenfy has shown significant efficacy in schizophrenia. This article provides an overview of Cobenfy's basic information, mechanism of action, pharmacodynamics, pharmacokinetics, safety, and clinical efficacy.

Objective: This study aims to analyze the utilization of real-world evidence (RWE) in the new drug application (NDA) process at the US FDA from January 2022 to July 2024, and to evaluate its impact on regulatory decisions. The findings will serve as a reference for RWE-based drug review decisions and new drug development by applicants. Methods: Through a comprehensive review of public resources on the FDA official website, we extracted and analyzed public documents of all new molecular entity (NME) NDA applications approved by CDER from January 1, 2022 to July 1, 2024, including proportion, type, data source and supporting role of RWE in NDA. The feedback from the FDA on RWE research was also summarized, including issues such as study design, data quality, and control of bias and confounding factors. Results: The study found that among the 77 NDA applications included in the review, 36 (47%) included RWE studies; 19 (53%) only supported safety, 6 (17%) only supported efficacy, and 11 (30%) supported safety and efficacy; 9 (25%) were submitted as primary evidence, and 27 (75%) were submitted as supporting evidence; 17 (47%) of the 36 approvals were for rare diseases. The FDA's feedback on RWE studies mainly focused on research design issues, data quality issues, and insufficient control of bias and confounding factors. Conclusion: RWE is increasingly utilized in new drug applications, but the FDA has raised many limitations in the review process. In order to make RWE better support the review decisions, applicants should focus on the scientificity and rigor of the study design, the reliability and relevance of the data source, and the transparency of the research process, and adopt high-quality data and scientific research design to improve the applicability and reliability of RWE in NDA.

With the continuous development of information technology in drug regulation, countries such as the United States, the European Union, and Japan have established electronic submission systems by integrating information technology and drug registration to enable online submission and reception, promote the deepening and implementation of the reform to the drug review and approval system, and enhance service level through website integration and public information. This paper studies the functions and characteristics of the electronic submission systems in the United States, the European Union, Japan and other countries, in order to provide reference for the informatization construction of drug registration electronic submission in China, promote the efficiency of electronic submission, increase quality and speed of review and approval, and strengthen the service efficiency of drug regulation by “internet plus”.

The registration testing is a prerequisite for the marketing of drugs. This paper aims to continuously promote the applicants for drug registration to provide scientific and standardized reporting information and samples, thereby assisting the inspection agency to accurately assess the sample quality and to improve the quality and efficiency of the registration testing process. By reviewing the relevant provisions in registration and inspection in “Provisions for Drug Registration” and “Drug Registration and Inspection Work Procedures and Technical Requirements Specification (for Trial Implementation)”, this study examines the registration and inspection data review for overseas produced chemical drugs, summarizes the common issues in the registration and inspection combined with practical experience, analyzes their underlying causes, and puts forward strategies and solutions. The study found that many registration applicants lack a comprehensive understanding of the registration and inspection procedures related to overseas produced chemical drugs. Issues identified include technical information, quality standards, samples and reference substances, etc. There are problems such as inaccurate information, mismatch of information, inconsistency between sample packaging materials and declarations, as well as insufficient residual validity period. It is recommended that regulatory agencies enhance training and guidance, accelerate the revision of policy documents, breakthrough the review and inspection of the communication mechanism, enable the applicant to in-depth study and understand the system documents, emphasize on the consistency issues, fully prepared for the pre-test and method development, in order to improve the quality of the declaration information, and efficiently complete the registration and testing.

Objective: Clinical trials of antipsychotic drugs involve unique patient management and ethical considerations, leading to a growing number of non-inferiority trials, where the selection of the non-inferiority margin (M₂) poses a significant challenge. This study uses aripiprazole, an active control drug, as an example to explore a rational method for selecting the non-inferiority margin, providing a reference for the design of similar studies in antipsychotic drugs. Methods: The total score reduction in the Positive and Negative Syndrome Scale (PANSS) was chosen as the primary endpoint. Following the FDA-recommended fixed margin method, and in consultation with clinical expert consensus, the M₂ was determined. First, based on literature data from aripiprazole versus placebo studies, a model-based meta-analysis (MBMA) was conducted to obtain the pharmacodynamic characteristics of the net effect of aripiprazole (after deducting the placebo effect) and to explore the influencing factors, providing a basis for pooled data analysis across different treatment durations. Second, a meta-analysis was conducted using data from aripiprazole versus placebo studies to estimate the treatment effect of aripiprazole and its 95% confidence interval (CI), with the lower bound of the 95%CI used as the entire effect (M₁). Subsequently, the range of M₂ values in antipsychotic clinical trials reported in the literature was collected, and the corresponding sample sizes were estimated. Combined with expert consensus on clinically acceptable sample sizes, M₂ was determined. Results: MBMA suggested that the therapeutic effect of aripiprazole approaches a plateau after 6 weeks of treatment. Meta-analysis estimated the net effect of aripiprazole after 6 weeks of treatment as 11.39 (95%CI: 9.72, 13.06), with M₁ being 9.72. The current clinical literature shows that M₂ values for non-inferiority trials in schizophrenia are widely distributed, ranging from 5 to 8. For generic drugs, assuming a one-sided α=0.025, a power of 80%, and a common standard deviation (SD) of 18, the estimated sample size per group is 122, corresponding to an M₂ of 6.5, which is similar to FDA's guidelines for clinical endpoint bioequivalence studies and can achieve bridging purposes. For innovative drugs, using approximately 50% of M₁ (9.72) as the non-inferiority margin, i.e., M₂=5, the corresponding sample size per group should be 205. Considering the difficulty of patient management and care, this is a clinically acceptable sample size. Conclusion: For non-inferiority trials using PANSS score reduction as an efficacy endpoint and aripiprazole as the control drug, an M₂ of 6.5 is appropriate for generic drugs, and an M₂ of 5.0 is appropriate for innovative drugs. This study provides important references and insights for selecting non-inferiority margins in similar trials involving other active control drugs.

Objective: To deeply understanding the development situation and registration characteristics of clinical trials for pancreatic cancer, and to provide insights into enhancing clinical research. Methods: A comprehensive search of all pancreatic cancer clinical trials on ClinicalTrials.gov was conducted up to July 3, 2024. The basic characteristics, methodological design, and key parameters of these trials were statistically analyzed. Results: A total of 4 409 pancreatic cancer clinical trials were searched worldwide, with 542 were conducted in China, both showing an upward trend. 1 705 (38.7%) trials had been completed, 971 (22.0%) were recruiting participants, and 434 (9.8%) had been terminated. These trials included 1 326 (30.1%) Phase Ⅰ trials, 1 550 (35.1%) Phase Ⅱ trials, and 249 (5.6%) Phase Ⅲ trials. Intervention studies comprised 80.0% of the trials, while observational studies accounted for 19.6%. The primary objectives of these trials were treatment (2 849, 64.6%), diagnosis (273, 6.2%), and supportive care (154, 3.5%). In terms of study design, 41.2% of the trials employed a single-arm design, 27.7% used a parallel design, and 6.1% utilized a sequential design. Additionally, 1 095 (24.8%) trials were randomized and 400 (9.1%) were blinded. The main interventions were chemotherapy (2 477, 56.2%) and surgery (684, 15.5%). Among the 249 Phase Ⅲ clinical trials, 94 (37.8%) used Overall Survival as the primary endpoint, 24 (9.6%) used Progression-Free Survival, with other common endpoints including adverse events (5.2%) and Disease-Free Survival (4.4%). Conclusion： The number of clinical trials for pancreatic cancer has rapidly increased. Chinese researchers should focus on improving trial design, pay more attention to diagnostic trials, enhance the application of randomization and blind methods, and select more scientific and objective end-point outcomes to further improve the clinical study of pancreatic cancer.

Objective: To study the potential toxicity of pediatric Reduning Injection (RDN) in weaning Beagle dogs (PND₄₉), a study was conducted for a 4-week administration period and a single-dose via intravenous injection. This research aims to support subsequent clinical risk assessment for children. Methods: In a single-dose toxicity study, weaning Beagle dogs (PND₄₉) were administrated for 30 mL stock solution per kg (78 g crude drug/kg) within 24 h following litter grouping. In a 4-week repeat-dose toxicity study, weaning Beagle dogs were administrated RDN (2.0, 5.0 and 10.0 mL of stock solution kg·day^-1) for clinical observation after Within-litter grouping, laboratory examination, autopsy and histopathology examination. And the toxicokinetics parameters such as T_max, AUC and C_max were calculated. Results: In the single-dose toxicity study, no significant toxic reaction was observed in the pediatric RDN. In the second study, signs related to amplification of pharmacological effects were observed only in weaning Beagle dogs in each dose group, and no significant signs of toxicity related to the test article were observed. All the examinations and parameters were normal. Furthermore, the process of exposure and elimination of pediatric RDN exhibited linear dynamic characteristics. Conclusion: The MTD of RDN exceeds 78 g crude drug/kg, while the NOAEL was 26.0 g crude drug/kg (It is 10 times the equivalent dose of dogs, 20 times the clinical dose, and 33.3 times the pharmacodynamic dose).

With the global attention to animal welfare and the progress of science and technology, more efficient and accurate in vitro models for teratogenicity evaluation have gradually emerged. These models include embryonic stem cell test (Embryonic Stem Cell Trials, EST), microculture test (Microcarrier Culture Trials, MCT), whole embryo culture test (Whole Embryo Culture Test, WEC), and the models based on human induced pluripotent stem cells (Human Induced Pluripotent Stem Cells, hiPSC). They provide a methodological supplement for in vivo embryonic developmental toxicity testing. In particular, hiPSCs, with the ability to differentiate into all cell types in vivo, have become a key model for constructing complex embryonic development models, simulating specific developmental stages and conducting directed organ differentiation studies. With the development of three-dimensional cell culture technology, organoid system, high-throughput screening and organ chip technology, in vitro models have made remarkable progress in simulating human organ microenvironment, co-culture of multiple cell types and reconstruction of organ 3D structure and function on micro-platform. These advances not only improve the efficiency of drug screening, but also enhance our understanding of how drugs interfere with embryonic development. Although the current models still face challenges of physiological relevance, complexity, and ethics, they show great potential in assessing drug safety.

Radiopharmaceuticals are the “soul” of nuclear medicine, capable of correlating the molecular mechanism at the micro level with the macro disease phenotype. They are extensively utilized in the diagnosis and treatment of clinical diseases and constitute the cornerstone of precision medicine. Currently, there are two primary approaches for radionuclide labeling of radiopharmaceuticals. Non-metallic radionuclides are directly linked to the carriers through covalent bonds, and the binding effect is robust. Conversely, radiometallic nuclides require chelating agents to form coordination bonds and then bind to ligands, and the binding effect is relatively weak. Thus, covalently labeled binding methods are more appealing in the development of radiopharmaceuticals. This paper primarily presents the covalent site-specific labeling strategy and its application progress in radiopharmaceuticals, aiming to offer reference for relevant radiopharmaceutical development.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease whose causes and pathogenesis are related to epithelial-to-mesenchymal transition and myofibroblasts. The median survival time of patients with this disease is only 2~3 years, and the mortality rate is higher than that of most tumor diseases. Therefore, it is very important to find a new treatment method. Hepatocyte growth factor (HGF) is a polypeptide growth factor that has a variety of biological effects, especially a positive role in anti-fibrosis aspect. In this review, we summarize the biological characteristics of HGF and cellular-Mesenchymal epithelial transition factor (c-Met), and HGF/c-Met axis-related signaling pathways, and highlight the multiple roles of HGF in the treatment of pulmonary fibrosis-related diseases, such as maintaining the survival of epithelial cells and endothelial cells, inhibiting the aggregation of myofibroblasts and epithelial-to-mesenchymal transition. In addition, we further analyze the feasibility of using HGF in the treatment of IPF and discuss its potential therapeutic advantages and possible challenges or limitations, in order to provide a theoretical reference for future research directions and clinical application strategies in this field.

Liver diseases, with their insidious nature, are regarded as a great challenge in the medical community, threatening the life, health, and quality of life of countless patients. In addition, patients with liver diseases are widely distributed and their incidence is on the rise, but current drug treatments are often difficult to control the progression of liver diseases, and it has become imperative to search for effective drugs for the treatment of liver diseases. The active ingredients of traditional Chinese medicine are widely used in treating liver diseases for their special therapeutic effects. With the deepening of research on biomimetic nano drug delivery systems (BNDDs), the prominent in vivo long-circulation effect and excellent targeting ability make them a new carrier of active ingredients of traditional Chinese medicine, which has a very bright application prospect. The aim of this review is to summarize the research progress of different types of traditional Chinese medicine active ingredients and their BNDDs in treating liver diseases, with the aim of providing references and new ideas for the treatment of liver diseases with novel biomimetic formulations of traditional Chinese medicine.

Objective： To observe the efficacy and safety of Qiangli Loquat Dew (sugar free type) in improving cough symptoms of pneumoconiosis patients. Methods： A comparative study was undertaken to enroll hospitalized patients with pneumoconiosis and cough symptoms at the Hunan Provincial Institute of Occupational Disease Prevention and Control, spanning the period from January 1, 2023, to December 31, 2023. Patients were divided into the study group and the control group based on whether they received Qiangli Loquat Dew during their hospitalization. Before treatment and on the 5th day of treatment, clinical efficacy evaluation, cough evaluation test (CET), cough visual analogue Scale (VAS) and the modified Medical Research Council (mMRC) were performed on patients in both groups, and propensity score matching analysis method was used to match patients in both groups. After matching, the groups were compared in terms of clinical effectiveness, alleviation of cough symptoms, and the occurrence of adverse reactions. Binary logistic regression was used to analyze the pneumoconiosis patients who were more likely to benefit from the treatment of Qiangli Loquat Dew. Results： A total of 1 801 patients were enrolled in the study, while the control group consisted of 195 patients. Before matching, there were notable differences in age and smoking prevalence between the two groups, with statistical significance (P<0.05). Following a 1∶1 propensity score matching approach, 186 patients were selected from each group. After a five-day treatment period, the study group exhibited a notably higher clinical overall response rate compared to the control group. Additionally, the study group exhibited significantly higher improvements in the CET and VAS scores for cough compared to the control group, with statistical significance (all P<0.05). While both groups showed improvement in the mMRC dyspnea scale scores, the magnitude of improvement did not differ statistically between the two groups. Additionally, there was no notable difference in the incidence of adverse reactions between the two groups (P>0.05). The binary logistic regression analysis indicated that patients without chronic cough and those in a non-smoking condition (including those with no smoking history or who have quit smoking) had a superior overall clinical response rate compared to patients who suffered from chronic cough and were smokers (P<0.05). Conclusion： Qiangli Loquat Dew effectively alleviates cough symptoms and enhances clinical outcomes in pneumoconiosis inpatients, without elevating the occurrence of adverse reactions. Patients with non-chronic cough and non-smoking status (no smoking history or cessation) have a better curative effect than patients with chronic cough and smoking and are more likely to benefit from the treatment.

Objective: To provide reference for the development of vaccine clinical trials in Chinese pediatric population. Methods: Information related to vaccine clinical trials in Chinese pediatric population was collected from the website Chinadrugtrials.org.cn, which was statistically analyzed in quantity of registered trails in each year, trial stages, vaccines types, trial types, insurance, etc. Results: From September 6, 2013 to December 31, 2023, a total of 430 clinical trials involving pediatric population were registered on the website. Among these clinical trials, many trails were during phase Ⅲ. All vaccines used in the trials were preventive vaccines, and combined vaccines were the research focus. The homogenization of vaccine researches became a serious problem. The trials were mainly initiated by enterprises, among which rare trials started in three-tier medical institutions. Only 2 trials were classified as multi-regional clinical trial. 120 trials were purchased insurance. Conclusion: Although vaccine clinical trials in Chinese pediatric population have developed steadily in recent years, but there is obvious gap in vaccine research between international standards and China, so it is necessary to accelerate the development of vaccine clinical trials in pediatric population.

Objective: To optimize the preparation process of Ting Liu granules and establish its preparation characteristics map. Methods: The wetting agent, material/auxiliary ratio, flavoring agent type and dosage, and auxiliary material type were investigated, and the D-optimal mixture design method was adopted to screen out the optimal auxiliary material ratio by taking molding rate, rest-angle, and moisture absorption as the investigation indexes. At the same time the feature maps of 15 preparation were established. Results: The best preparation process was wet granulation with 100% maltodextrin-soluble starch-sodium carboxymethyl cellulose (6∶2∶1) as filler, 10% xylitol as flavoring agent, 80% ethanol as wetting agent. Eleven characteristic peaks were established based on the HPLC feature maps of 15 batches of samples, and five chromatographic peaks were identified according to the reference substances. Conclusion: The optimal preparation process and characteristic mapping method of Ting Liu granules are stable and feasible.

Objective: To establish a rapid, sensitive and convenient LC-MS/MS method for determination of trilaciclib in rat plasma and investigate its pharmacokinetic characteristics. Methods: The plasma samples were pretreated by protein precipitation method with organic solvent, and acetaminophen was used as internal standard. The analytes were separated on a Thermo hypersil goldtm^TM column (50.0 mm×2.1 mm，3 μm), and the mobile phase was gradiently eluted with 0.1% formic acid-water (A) and acetonitrile (B) at a flow rate of 0.45 mL·min^－1. Positive ion mode of electrospray ion source and multiple reaction monitoring were adopted. The ion pairs of trilaciclib and internal standard were m/z 447.2→336 and m/z 152→110.1, respectively. Results: Trilaciclib was not affected by plasma matrix, and had a good linear relationship between 10~5 000 ng·mL^－1 (r=0.995 07), with the lower limit of quantification being 10 ng·mL^－1. The intra-assay and inter-assay precision RSDs were ≤9.45%, with good stability. The methodological validation was in line with the provisions of Chinese Pharmacopoeia (2020 Edition). Conclusion: The method is rapid, simple, and specific, which is suitable for investigating the pharmacokinetic characteristics of trilaciclib in rats, which provides a methodological reference for the in-depth clinical study of trilaciclib, a new CDK4/6 inhibitor.

Objective: To conduct a Meta-analysis to evaluate the clinical efficacy and safety of Compound Cortex Phellodendri Liquid for treatment of herpes zoster, thus to provide evidence-based medical evidence for clinical treatment of herpes zoster. Methods: Databases including PubMed, Embase, the Cochrane Library, CNKI, and Wanfang were searched to collect randomized controlled trials (RCTs) about Compound Cortex Phellodendri Liquid in the treatment of herpes zoster from inception to March 2022. Meta-analysis was performed by using RevMan5.3 statistical software. Results: A total of eight RCTs involving 568 patients were included. The result of Meta-analysis showed that Compound Cortex Phellodendri Liquid produced a statistically significant improvement for a higher effective rate in Herpes zoster (RR＝1.46，95％CI （1.23，1.74），P＜0.000 01). Two studies described the analgesic time and scab forming time of the experimental group and the control group, and there was significant difference between the two groups (P<0.05). Two articles described the VAS scores of the experimental group and the control group, and there was significant difference between the two groups (P<0.05). One study described herpes zoster rash scores in the experimental and control groups. After treatment, the herpes zoster rash scores (the number of blisters, number of blisters, change of blisters, and the area of erythema of the two groups were lower than those of the control group (P<0.05). One study described the comparison of the levels of IL-2, IL-6, IL-8, and PGE2 between the experimental group and the control group. After treatment, the levels of IL-2, IL-6, IL-8, and PGE2 in the experimental group were lower than those in the control group (P<0.05). One study described the treatment satisfaction of two groups of patients. The results showed that 88.6% of the satisfaction in the experimental group was higher than 60.0% in the control group, and there was significant difference between the two groups (P<0.05). One study described the occurrence of adverse reactions in the experimental group and the control group. Conclusion: Compound Cortex Phellodendri Fluid is an effective and safe external preparation for treating herpes zoster. More high-quality RCTs need to be carried out to confirm the present findings.