Objective: Drug resistance and endogenous cross-reactivity are the main factors affecting the detection of anti-drug antibody (ADA), so the establishment of method that can tolerate higher drug concentration and avoid endogenous cross-reactivity is a major problem to be solved in immunogenicity analysis. The aim of this study was to establish and verify a method for detection of ADA against recombinant human serum albumin (rHSA). Methods: Anti-rHSA antibody was extracted by acidification and enrichment with magnetic nanobeads and then detected using a bridging method. Finally, the established method was validated. Results: The recovery of the antibody was greater than 80% by using the established method. The sensitivity of the method could reach 0.5 μg·mL^-1 and the intra- and inter-batch RSDs were less than 20%. In addition, the method could resist drug of up to 2 mg·mL^-1. Conclusion: This study established a method for the detection of anti-rHSA antibody. The method has high antibody recovery and good performances of sensitivity and precision. It can also achieve mg-level drug-resistance and effectively remove the interference of endogenous substances, which can be applied for the detection of ADA, extraction of antibody drugs and further analysis of drug metabolism.

As the use of cell therapy products such as chimeric antigen receptor T cells (CAR-T) is getting matured, there has been an increasing interest in the methods used to test the quality of cell therapy products. In vitro viability assay is an important method for evaluating the effectiveness of cell therapy products and is also widely used in the product release process because of its simplicity and rapidity. In this paper, we review the in vitro potency determination methods for cell therapy products such as CAR-T from the perspective of both effector cells and target cells.

Objective: To evaluate the anti-platelet aggregation effect and advantages of Quansanqi tablets (PSQ), an innovative new drug of Panax notoginseng. Methods: Human platelet-rich plasma and washed platelets were used to detect the platelet aggregation rate and calcium ion concentration induced by different platelet activators; rat platelet-rich plasma was used to compare the platelet aggregation rate induced by ADP in PSQ and Panax notoginseng extract; gastric bleeding model rats were established by injecting 80% ethanol to investigate the effects of PSQ and aspirin on fecal occult blood; the hemostatic effect of PSQ was observed by mouse and rat coagulation test. Results: PSQ could dose-dependently inhibit ADP, thrombin, U46619, collagen and reduce anti-CD9-induced human platelet aggregation rate (P<0.01) and Ca²⁺ release (P<0.05 or P<0.01); it could inhibit ADP-induced rat platelet aggregation rate (P<0.01), with significantly better effect than Panax notoginseng extract. PSQ could reduce the fecal occult blood grade in gastric bleeding model rats (P<0.05), while aspirin could not (P>0.05); it could also significantly shorten the coagulation time in mice and APTT time in rats, indicating certain hemostatic effect. Conclusion: PSQ has significant anti-platelet aggregation effect through multiple ways with multiple action targets, and can also reduce the risk of bleeding because of its excellent hemostatic effect, which is a safe and effective new antiplatelet drug.

Objective: To explore the effective compatibility ratio of the 5 main active ingredients in Gardenia and Panax notoginseng by uniform design test method thus to provide preliminary experimental evidence for clinical treatment of Alzheimer's disease. Methods: A model of SH-SY5Y cell injury induced by β-amyloid (Aβ_1-42) was established, and the cell survival rate was used as an indicator to study the effective concentrations of the main active ingredients against Aβ_1-42-induced SH-SY5Y neuronal injury, and according to the damage recovery rate, five ingredients with better efficacy were selected. On this basis, the five components with good efficacy were used as independent variables X₁, X₂, X₃, X₄ and X₅, respectively, the injury recovery rate (%) as the dependent variable Y, U₂₁ (21⁵) uniform design table and 2 mathematical models of linear and quadratic polynomials were selected, and the variables were screened by stepwise regression method to determine the effective compatibility ratio of the 5 active ingredients. Results: The main active components of Gardenia-Panax notoginseng, except genipin, could increase the cell survival rate of SH-SY5Y cells induced by Aβ_1-42 in a concentration-dependent manner. 5 ingredients with good efficacy were identified as notoginsenoside R1, ginsenoside Rb1, ginsenoside Rg1, geniposide, and genipin gentiobiglycoside. The results of uniform design experiments were obtained by regression analysis and Y=12.775 019 92-0.493 827 042 7X₂+0.070 634 665 58X₁X₂-0.022 126 968 533X₁X₅+0.053 000 691 95X₃X₄ (r=0.857 4, F=11.105 9, P=0.002), and the uniform design test verified that the best combination ratio was notoginsenoside R1∶ginsenoside Rb1∶ginsenoside Rg1∶geniposide∶genipin gentiobiglycoside=1∶1∶1∶1∶0. Behavioral experiments showed that compared with the model group, the number of tests and memory errors of donepezil hydrochloride group and gardenia-Panax notoginseng optimal matching were significantly reduced. The results of ROS and Western blot showed that compared with the model group, the optimal combination of donepezil hydrochloride group and gardenia-Panax notoginseng could effectively reduce the fluorescence intensity of ROS and the expression of RAGE protein. Conclusion: The optimal matching ratio obtained by uniform design screening can effectively improve Alzheimer's disease, and its mechanism of action may play an anti-Alzheimer's effect by inhibiting the activation of RAGE-ROS pathway, which provides an experimental basis for the treatment of Alzheimer's disease.

Drug regulatory science is a cutting-edge task in the field of drug regulation that has received much attention from the international community in recent years. Currently, different countries and regions have different foundations for drug regulatory industries, are in different stages of development, and face different prominent issues. Therefore, the focus of drug regulatory science and the problems that need to be solved are also different. The origin of drug regulatory science suggests that we should deeply consider the emergence and development of drug regulatory science from the perspective of the arrival of a new era and the emergence of new forces. The definition and characteristics of drug regulatory science suggest that it is a practical science that solves prominent problems and directly serves regulatory decision-making, and future studies should focus on drug regulation rules, develop new regulatory tools, standards and methods, and cultivate new theories, regulations and mechanism.

The intake of food could lead to various changes in the physiology of human gastrointestinal tract, such as the pH of the gastrointestinal, ionic strength, buffer capacity, the time of gastric emptying, visceral blood flow, and the metabolizing enzymes. These physiological changes would have effects on the release, absorption, distribution, metabolism, and/or excretion of a drug, leading to changes in its pharmacokinetics. Therefore, it is of great importance for clinical research and prediction of the food effect on novel drugs to understand the manner of change in the luminal condition of human gastrointestinal caused by food intake, as well as the manner of the effect on bioavailability. In this paper, we summarized the clinical trials about the food effect on drugs in clinical trial databases and literature first. Then, the guidelines relevant to clinical trials on food effect issued by the National Medical Products Administration (NMPA) of China, the United States FDA, and EMA were compared and summarized. Finally, taking the antitumor novel drugs as an example, we summarized and analyzed the clinical trials about food effect registered in China in the past 10 years, focusing on the main factors related to the food effect in the development of novel drugs, the official guidelines, as well as the current status of research in China, aiming to provide basic research data about the food effect for the development of novel drugs in China.

Fumagillin is a natural insoluble antibiotic isolated and purified from the liquid fermentation medium of Aspergillus fumigatus. Fumagillin and its derivatives have been found to have a variety of biological activities such as anti-tumor, anti-obesity and anti-microsporidiosis, so they are widely used in the field of medicine. The molecular structure properties, biological activity, application and mechanism of action of fumagillin and its several common derivatives based on C6 site modification, such as fumagillin B, TNP-470, CKD-732 and PPI-2458 are reviewed in this article, and the separation and purification process, activity research and application prospect are prospected in order to provide reference for the further application of low toxic fumagillin and its derivatives in clinical practice and research.

Patents have long been considered as the most important way to protect pharmaceutical innovations, and the drug patent system has exerted a profound impact on the development of the pharmaceutical industry. In the context that domestic effective drug regulations and patent laws and regulations have covered the provisions on drug patent linkage system, this paper, by taking the first case of domestic drug patent linkage litigation as an instance, analyzes the trial effect of the newly launched drug patent linkage system in China, explores its impact on the generic drug industry, and tries to give suggestions to generic drug enterprises on the choice of patent application types and the authenticity of application materials. The research-based pharmaceutical enterprises need to seize the opportunity to safeguard their rights and protect themselves against patent infringement by choosing an appropriate method to resolve patent disputes. Moreover, given the constraints of China's binary separation of procedures of patent infringement and patent invalidation on the early solution of pharmaceutical patent disputes and the problems awaiting to be solved in different types of patent applications, this paper also puts forward related suggestions on patent protection, including the necessity of timely review and analysis of the implementation of the patent linkage system, enhancement of the legal status of administrative adjudication to enable some authorities of administrative confirmation, and the necessity for clearer definition of types of patent applications and further standardization of patent infringement cases under different circumstances.

Clinical orientation is the expected therapeutic effect of drugs on diseases, and accurate clinical orientation is the key to successful development of new drugs and clinical rational drug use after marketing. The rationality of clinical orientation for traditional Chinese medicine should be evaluated from the aspects of research drugs, targeting diseases, existing therapeutic drugs and review requirements. The methods and basis of clinical orientation include human experience, theory of traditional Chinese medicine, basic researches and clinical trials. By selecting reasonable clinical orientation and taking clinical value as the guidance, the curative effect of traditional Chinese medicine can be truly reflected, and the quality of research and development and success rate of new Chinese medicine will be improved.