biochemical drugs is derived from organisms and contains many active substances such as peptides, polysaccharides and amino acids. In order to improve the quality control of biochemical drugs, it is the key to formulate quality standards that can identify the authenticity, evaluate the pros and cons, and monitor the quality stability and uniformity. Methods: Fingerprint, which has been scientifically evaluated, is an advanced means to effectively analyze complex biopharmaceuticals. Results: Through the basic study of fingerprint, the scientific detection method can comprehensively and systematically reflect the overall information of the effective components. Conclusion: The fingerprint of biochemical drugs is a systematic study involving many subjects, which is original and novel, and is of great significance for improving the overall level of biochemical drugs in China. & Mg; R
biochemical drugs is a basic substance with biochemical activity, which is obtained by separation and purification from organisms or their metabolic secretion products, and is used to prevent, treat and diagnose diseases, including such substances made by chemical synthesis or modern biotechnology. One of the important basic characteristics of biochemical drugs is that it is derived from organisms. Second, it is the basic biochemical component in organisms. These basic biochemical substances mainly include; Amino acids, peptides, protein, enzymes and coenzymes, polysaccharides, lipids, nucleic acids and their degradation products all have various biological activities or physiological functions [1 ~ 2]. MAxU7~z5q/
The research and development of biochemical drugs abroad is relatively early. From the 193s to the present, it is gradually developing in the direction of safety, standardized management, refining and purification, and high activity and clear composition preparation by bioengineering means. Although biochemical drugs research was carried out late in China, the comprehensive utilization cost is relatively low because China is a big country in animal husbandry and feeding industry, and the raw materials of biochemical drugs are slaughtered and processed as edible animals. In addition, biochemical drugs is easily absorbed and utilized by human body, with good safety and definite curative effect, which has been widely used in clinic, and the state attaches great importance to it. Therefore, special competent institutions have been set up for planning and management, and preferential policies have been given to support it, especially in modern medicine, life sciences and the improvement of biotechnology. It has promoted the rapid development of biochemical drugs's industry. The level of scientific research and technology in biochemical drugs has improved rapidly and developed rapidly. There are many kinds of products researched and developed. Only before 1998, there were more than several hundred kinds in biochemical drugs. However, there are serious quality problems, such as repeated varieties, inconsistent standards for the same varieties, and uncertain curative effects, which have caused some confusion and accidents in drug administration. The national drug administration department attached great importance to improving the quality of drugs, and unified rectification and standardization of quality standards for biochemical drugs nationwide began in 1998, which was completed in 22. It has been greatly improved in ensuring safety, effectiveness and quality standards. Including thymosin for injection, cerebroprotein hydrolysate injection, cattle encephalon glycoside and ignotin injection and bone polypeptide injection, nearly 1 kinds of biochemical drugs are widely used in clinic at present, and the effect is generally good. Nevertheless, there are still many serious problems in production and quality management in biochemical drugs, mainly in the following aspects: X "Wajks. < P > 1. Existing problems. PS | D | L-< P > 1. There is no strict quality control of materials. _ xvv4
At present, the sources of edible livestock and poultry organs in biochemical drugs are quite confusing. The market economy has diversified the breeding industry, and there are still many problems in the unified slaughter of meat livestock and poultry. It is difficult to do routine simple diseases and pathogen quarantine seriously, and the accidents are very eye-catching. The problem of "reassuring meat" has attracted great attention from the state. There are serious hidden dangers in the quality and safety of organs and tissues obtained from this. In addition, human and livestock suffering from diseases like avian influenza, mad cow disease, SARS and foot-and-mouth disease which ravage the whole world have also attracted great international attention. (4) Because the state has not formulated inspection standards and items for medicinal animal organs, at present, various biochemical drug manufacturers directly process and produce the purchased animal organs, which can be said to be without any inspection and quarantine, and even less do they certify the health and quarantine of the meat animals. In addition, it is common to use growth promoters and veterinary drugs for raising livestock and poultry, and it is also very common to raise pigs in bulk and garbage. As a result, pollutants and pathogens (5) and (6) in animals, especially in organs, pose serious pollution to biochemical drugs that are directly injected in vivo, and the safety hazard is very serious. The state has instructed China Institute for the Control of Pharmaceutical and Biological Products to hold a special seminar to formulate corresponding measures to control such problems. $; . oyJ
1. 2 The production process is not standardized. 2PtDVT
At present, most varieties in biochemical drugs, especially in biochemical drugs, where organs are extracted, do not have strict requirements on raw material selection, processing and finished product production technology. Especially at present, the phenomenon of entrusted processing of raw materials and outsourcing of semi-finished products is very common, so it is difficult to ensure the uniformity and controllability of the final quality of biochemical drugs products with complex components. In addition, there are problems in monitoring pollutants such as heavy metals and organic solvent residues in organ processing and production, and inactivating possible pathogens and other key production links. But also bring hidden danger to that safe use of biochemical drugs (1). WixD> C
1. 3 standard is not controllable. /B2#j"8x
Now it has been promoted to the quality standard of biochemical drugs, which is being implemented by the national standard. Most of them do not fully combine the complex characteristics of the components of biochemical drugs, but also follow the technical requirements of the quality standard of chemical drugs. Although they learn from the advantages of foreign biochemical drugs ("cerebrolysin" and "Aiweizhi") quality standards, they only make a rough qualitative and quantitative analysis of the main effective components, mostly single components and single compounds among various components. For example, qualitative identification of protein or polypeptide by HPLC, SDS-PAGE, etc. can only reflect the similarity of components such as main active ingredients, and although activity index detection items are added to further verify biological activity, they are not specific enough to fully reflect the quantitative information of efficacy characteristics of various active ingredients, and can not truly identify the true and false and evaluate the pros and cons. }dY< 9yY%
Especially in biochemical drugs from animal organs, such as thymosin injection varieties, there are many biochemical substances with activity and function in the components, and the composition of drug effect is not very clear, which is often influenced by raw materials, auxiliary materials, reagents, technology and other factors, and the components will change, which will directly affect the clinical efficacy and the occurrence of toxic and side effects. Only by strictly controlling the source and quality of raw materials, strictly standardizing the process of raw materials, strengthening the monitoring of production processes, strictly inspecting semi-finished products, and stipulating the quality standards of finished products with detailed, rapid qualitative and quantitative inspection items with high specificity and accuracy, can the quality of biochemical drugs be ensured to be safe, effective and controllable (3). Urkersen
2. The key to quality control in biochemical drugs is to work out quality standards that can distinguish authenticity, evaluate advantages and disadvantages, and ensure quality stability and uniformity. DSmD/4D8
Fingerprint Spectrum or Fingerprint is a comprehensive and quantifiable identification method, which is mainly based on modern analytical techniques, and is widely used in biochemistry, molecular biology, genomics and other research fields. Among the standards of applying fingerprint to plant drugs in foreign countries, Japan, the United States, France and Germany not only use it for plant drug research, but also evaluate it as an important indicator of new drug research. Our country also attaches great importance to the study of fingerprint, which is an important work to promote the modernization of traditional Chinese medicine. In 22, the State Food and Drug Administration clearly stipulated that all registered varieties of traditional Chinese medicine injections must be declared, and relevant fingerprint research materials must be declared, including three aspects of traditional Chinese medicine raw materials, extracts and products, and the correlation of fingerprints must be scientifically compared and analyzed, and the results are consistent before approval can be carried out (7). It has played a great role in improving and standardizing the quality of traditional Chinese medicine, and achieved remarkable results. Therefore, the state has given strong support to the fingerprint of traditional Chinese medicine from both policies and funds, and promoted it as an important work of the national industrial policy of modernization of traditional Chinese medicine. UNq(
) is the same as traditional Chinese medicine which is derived from natural biological resources. In biochemical drugs, especially biochemical drugs which is derived from animal organs, such as thymosin products, the raw materials need to go through processing processes such as freezing, extraction, hydrolysis, purification, etc. The composition of the final product is complex, and the pharmacological effect is the result of the comprehensive action of all active ingredients. Therefore, it is more suitable to adopt the fingerprint method which can compare the integrity and fuzziness to reflect the characteristics of the effective components of drugs, and at the same time meet the requirements of drug quality standard control. After strict quarantine of raw materials from animals in biochemical drugs and pathogen inspection to ensure the safety of organs taken, it is very suitable to confirm and monitor the similarity of components of extracts, semi-finished products and finished products, especially to monitor and evaluate the quality of the same variety from different batches and manufacturers, to identify the authenticity and judge the merits and demerits of fingerprints. In addition, due to the production in biochemical drugs, mainly the production process of raw material extraction, the composition of active components in the final product is very affected. By incorporating fingerprint into the inspection items of quality standards, the specificity and strictness of quality standards are strengthened, and the standardization of production technology of products is directly standardized. Can effectively ensure the stability of product quality. d@V; XC
Up to now, there is no method to comprehensively reflect the complex quality differences in biochemical drugs in the production and quality control of biochemical drugs at home and abroad, and there are some studies on fingerprint in physiology, pathology and animal organ extracts abroad (11), (12) and (13). Pharmacopoeia of developed countries does not specify the fingerprint in the quality inspection items of biochemical drugs, and the research on fingerprint in biochemical drugs is still blank. Based on the experience gained in the research of traditional Chinese medicine, the fingerprint was applied to the quality research and quality standards of biochemical drugs, and the raw material extraction, intermediate processing, finished products and quality stability were strictly monitored to ensure the quality of biochemical drugs in an all-round way. It will have international innovation and independent intellectual property rights. It will also lay a theoretical foundation for the development of biochemical drugs in China. Therefore, the study and determination of biochemical drugs fingerprint is the key to improve the overall level of biochemical drugs in China, and it is also an important measure to upgrade the quality of biochemical drugs to the international level. ]TQ)3=
2.1 Basic research work of fingerprints in biochemical drugs sKnXo l
The research and analysis of fingerprints in biochemical drugs is a research topic involving the interdisciplinary and comprehensive application of analytical chemistry, biochemistry, biological separation technology, physiology, pharmacology, bioinformatics and other disciplines. It involves a wide range of research disciplines and needs a large amount of research work. Applying fingerprint to the quality control of biochemical drugs production is a systematic project involving many production quality management factors. Drawing on the research experience of traditional Chinese medicine fingerprint, the fingerprint determination of biochemical drugs must be based on the characteristics of biochemistry and activity in biochemical drugs, including the information of all effective components. It is an effective component analysis and quality characteristic research under the guidance of biological activity and pharmacological action, not from the research of structure-activity relationship and molecular pharmacology of a chemical component, but from the comprehensive point of view of active component groups or groups, and is not limited to the study of surface physical and chemical properties of components, but scientific and reasonable. Perfecting the related basic research work is the key and prerequisite to develop the fingerprint of biochemical drugs. obm|!