Duan Jiachuan: pharmacology and toxicology of new drugs and interpretation of drug-forming properties

With the introduction of the national innovative drug policy, research institutes and drug research and development enterprises have been enthusiastic about the research and development of new drugs The research on the pharmacology, toxicology and drug-forming properties of new drugs can effectively guarantee the listing of valuable new drugs as soon as possible, and improve the drug safety and quality of life of patients Mr Duan Jiachuan, senior project manager of Chengdu Huaxi Haiqi Pharmaceutical Technology Co., Ltd., combined with more than ten years of industry practice and new drug research and development experience, explained the effectiveness of new drugs from the study of drug generation and toxicology, and shared the challenges and solutions brought by new technology drugs New drug R & D into drug evaluation new drug refers to a drug that has not been marketed in China or abroad Traditional research and development of new drugs need four basic stages: target research, drug screening, discovery of lead compounds and optimization of structure, and confirmation of candidate compounds in preclinical research It is a process that consumes huge financial, material and human resources, which is very difficult How to optimize this process through existing technology and knowledge of safety assessment is very important The traditional research and development mode of new drugs has gradually changed Many new drug research and development hope to combine the results of pharmacological and toxicological research in the clinical stage of drugs, and exclude unsuitable drugs from the new drug research and development pipeline in the early stage of research and development Naturally, this puts forward a high standard requirement for the formation of new drugs, which requires a very rich experience in order to give correct guidance in the optimization process stage As we all know, the evaluation principles of new drug research and development and early screening are well known In the principles of new drug research and development, the most important one is safety, the second is effectiveness, and the third is quality control In the principles of new drug screening, which are closely related to drug-forming evaluation, there are also three important factors The first is correct target, clear the relationship between disease and target, and clear the effectiveness of drugs for treatment The target has predictable biomarkers available; the second is the correct tissue, the compound needs to have bioavailability in the body when it is developed, and the drug can reach the target tissue when it is delivered; the third is the correct safety, clear the definition of safety, observe the maximum toxic reaction dose, and help the follow-up research and development; the combination of the three is better in the research and development of new drugs In the early stage, the drug properties were evaluated The R & D of improved new drugs is to optimize the structure, dosage form, prescription process, route of administration and indications of the drugs on the market, so that they have obvious clinical advantages At present, the improved new drugs have become the mainstream of new drug research and development in the world The improved new drugs include four situations, namely, structure optimization (category 2.1), preparation innovation (category 2.2), new compound preparation (category 2.3), and new indications for new use of old drugs (category 2.4) At present, the improved new drugs emphasize differential research and highlight the advantages of clinical research In the process of experimental design, the corresponding pharmacodynamics and pharmacology experience are provided according to the existing basis and advantages of efficiency and toxicity reduction It is the first choice to recommend pharmacokinetic study According to the results of pharmacokinetic study, determine the toxicity of follow-up drugs and set up clinical scheme The most typical example is atracurium The structure of atracurium is changed into CIS atracurium by optical isomer resolution, which can reduce the release of histamine and increase the research of histamine Secondly, according to the known active components, new drug administration ways are added to comprehensively study the changes of biological distribution and toxicity of drugs The above two points fully show that the improved new drugs reduce the risk of new drug research and development, and put forward high requirements for pharmacokinetic research In addition, we should also pay attention to your new indications of known active ingredients, such as the most widely used pediatric drugs in China, which are highly valued by the state Due to the differences in the development of children's organs, the physical development is not complete, which requires that the relevant laws and regulations, the corresponding time point of drug reaction in animals and human body, and the corresponding hair should be taken into account in the design of pediatric drugs Stage of education, etc Improved new drugs emphasize that there is a key clinical demand for the basis of setting up the topic Different drugs have different design points According to different design basis, relevant experimental design can be carried out, so that new technical drugs can be derived The challenge of new technology drugs new technology drugs in addition to biological agents, there are also traditional targeted immunotherapy, treatment to improve the microenvironment, immediate car-t treatment For immunotherapy, what should we do if many tumor immune related products are not combined with human body? This needs to be studied through different new methods and technologies New methods, technologies and tools are explained in the FDA white paper Because it is impossible to predict, it is generally found that the drug with greater toxic reaction can determine the human toxic reaction through the release of cytokines; therefore, many countries take this indicator as a clinical measurement consideration, i.e lower reaction In 2017, EMA issued "guidelines for bio similar drugs", recommending the minimum reflected dose to reduce the risk of clinical use of biotechnological drugs Mainly through the release of cytokines in vitro, the use of human blood for related research, to ensure the safety of drugs According to statistics, 84% of FDA's 32 tumor immune systems have conducted independent CRS clinical trials In a word, whether it's chemical medicine, biological preparation or improved new drug, pharmacology, pharmacokinetics and toxicology test of drug are essential, and judge whether it's ready-made drug or not and whether it's set for clinical use according to its research results Although the safety of new technology drugs is quite different from that of traditional drugs, it brings many challenges, but it is clear that independent drug research and evaluation It is necessary for pharmaceutical researchers to meet the basic technical requirements, obtain basic data to support the development of new drugs, control development risks and ensure the efficient and safe development of drugs Statement: this opinion only represents the author, not the position of yaozhi.com, welcome to exchange and supplement in the message area; if you need to reprint, please be sure to indicate the author and source of the article.