The improvement of people’s living standard requires more and better new drugs. The development of pharmaceutical science provides the theoretical basis and technical conditions for the development of new drugs. The competition of market economy also promotes the rapid development of new drugs. The US Food and Drug Administration (FDA) has approved more than 20 new drugs every year in the past ten years.
New drug development is a very strict and complex process. Although each drug is different, pharmacological research is an essential key step. Clinically effective drugs all have corresponding pharmacological effects, but drugs with positive pharmacological effects are not necessarily all clinically effective drugs. For example, antihypertensive drugs can lower blood pressure, but not all antihypertensive drugs are antihypertensive drugs, and they are not necessarily good drugs that can reduce complications and prolong life. Therefore, new drug development and research must have a gradual selection and elimination process.
In order to ensure the efficacy and safety of drugs for patients, the development of new drugs not only requires reliable scientific experimental results, but also the governments of various countries have formulated regulations on the approval and management of the production and marketing of new drugs, providing legal protection for people’s health and industrial and commercial economic rights. New drug sources include natural products, semi-synthetic and fully synthetic chemicals. In the past, the main method of drug selection was to rely on practical experience. Now, it is possible to search for close relatives according to the plant taxonomy of effective drugs for screening, or to infer the relationship between the chemical structure and pharmacological activity of effective drugs, and to synthesize a series of products in a targeted manner, and then conduct pharmacological screening.
In recent years, DNA gene recombination technology has been used for the inherent disease-resistant substances (protein components) in the body, that is, the specific gene segments of DNA are isolated and implanted into rapidly growing bacteria or yeast cells to obtain a large number of required protein drugs. In addition, existing drugs can be modified by chemical structure (semi-synthesis) or changed in dosage form, and drugs with better curative effect, less toxicity or more convenient application can also be obtained.
The new drug research process can be roughly divided into three steps, namely preclinical research, clinical research and after-sales research. Preclinical studies include systemic pharmacology studies in animals and observation of acute and chronic toxicity. For drugs with selective pharmacological effects, the absorption, distribution and elimination process of the drug in animals need to be determined before clinical trials. Preclinical research is to clarify the spectrum of action of the new drug and possible toxic reactions.
Clinical trials can only be conducted after preliminary approval by the drug regulatory authorities. The purpose is to ensure drug safety. In clinical research, 10 to 30 normal adult volunteers were first observed to observe the tolerance of the new drug to find out the safe dose. Then select patients with specific indications according to random grouping, set up a double control of known effective drugs and blank placebo (for acute and severe patients, no blank control that is harmful to the patient’s health), and try to use a double-blind method (patients and medical staff). can not distinguish the treatment drug or control drug) observation, and then carry out statistical analysis of the treatment results to objectively judge the curative effect. At the same time, it is necessary to monitor the blood drug concentration and calculate the pharmacokinetic data (see Chapter 3 for details). The number of tested cases should generally not be less than 300, and it can be expanded to more than three medical units for multi-center collaborative research after first in one hospital. For those new drugs that require long-term medication, there should be an observation record of 50 to 100 patients who have accumulated medication for six months to one year. Therefore, after the indications, contraindications, dosage and course of treatment and the description of possible adverse reactions are formulated, it can only be produced and marketed after the approval of the drug administration department.
Postmarketing surveillance refers to the social investigation and evaluation of new drugs after they are released into the market. In extensive promotion and application, it focuses on understanding the adverse reactions and long-term efficacy (including invalid cases) after long-term use. Drugs can only rely on the vast number of users (doctors and patients) to make a correct historical evaluation.
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Definition of new drug: refers to a drug whose chemical structure, drug composition or pharmacological action is different from that of existing drugs. The process of new drug research can be roughly divided into three stages: preclinical research, clinical research and post-marketing surveillance. Preclinical research consists of two parts: medicinal chemistry and pharmacology. The former includes drug preparation process routes, physicochemical properties and quality control standards, etc., while the latter includes pharmacodynamics, pharmacokinetics, and toxicity based on experimental animals. The purpose of scientific research is to ensure the safety, effectiveness and controllability of drug use. Preclinical pharmacology research is an insurmountable bridge stage in the whole new drug evaluation system engineering, and the conclusions obtained are of great value for the transition of new drugs from experimental research to clinical application.
Clinical studies of new drugs are generally divided into four phases.
Phase I clinical trials are preliminary clinical pharmacology and human safety evaluation trials conducted on normal adult volunteers. They are the initial stage of human trials of new drugs and provide scientific basis for follow-up research. Phase I is open, 20 to 30 cases, and the dose is explored.
Phase II clinical trials are randomized double-blind controlled clinical trials, the purpose is to select the best clinical application program.
Phase II: blinded, randomized, ≥100 pairs. Phase III clinical trial is an expanded multi-center clinical trial before a new drug is approved for marketing and during trial production. A new drug can be approved for production and marketing only after it has passed this phase of clinical trials.
Phase III: blinded, randomized, ≥300 cases. Phase IV clinical trial is the evaluation of the safety and efficacy of the tested new drug in a wide range of social population after the market. significance.
Stage IV: open, >2000 cases.