1. Identification of the structure of active ingredients of natural medicines and research on structure-activity relationships: Extraction, isolation, structure identification and activity research of active ingredients from plants native to Northeast China. Synthesis of natural medicines and research on structure-activity relationships. Research on anti-cancer, anti-viral, hyperlipidemia, and cardiovascular and cerebrovascular disease drugs.
2． Research on the chemical components of natural medicines and their biological activities: with the main goal of studying the chemistry of natural medicines, monomeric compound components are obtained through extraction, separation, and purification, and structural identification is carried out using spectroscopy and chemical means; leading compounds and biologically active compounds are discovered. Effective parts; research and development of innovative drugs.
3． Research on the chemical components of traditional Chinese medicine and their biological activities: The research content includes the extraction, separation, and structural identification of active ingredients in traditional Chinese medicine, focusing on the research on the new medicinal parts and the chemical components of the effective parts of authentic Changbai Mountain medicinal materials. Biological activity research is mainly conducted on the prevention and treatment of anti-cancer, antibacterial, treatment of diabetes, hyperlipidemia, cardiovascular diseases, etc.
4. Research on targeted drug systems: In order to make drugs better absorbed, improve drug bioavailability and achieve the best therapeutic effect, design and study targeted drug systems, so that drugs can be combined with or embedded in carriers to form a drug that can be A drug delivery system that is mobile in the body and releases drugs to target tissues, that is, uses a carrier drug release system to change the kinetic process of the drug, that is, it mainly changes the distribution of the drug in the body and only allows the drug to act on the target cells in the diseased area, while avoiding Effect on normal cells. It allows the drug to release one or more drugs in a specific part of the body at a predetermined rate within a specific period of time, and can control the metabolism rate of the drug.
5. Structural identification of natural drugs and research on structure-activity relationships: Taking China's unique Chinese herbal medicines and natural products as the main research objects, comprehensively applying the latest theoretical and experimental techniques of chemistry (mainly spectroscopy technology) and biology, the research findings Develop lead compounds that may become new drugs and conduct relevant basic theoretical research. At the end of the 19th century, there was a rush to find chemicals with medicinal value. Paul Ehrlich (1854-1915) was one of the most enthusiastic explorers of chemotherapy. Although his research work can be traced back to the 1870s, his major contributions were only applied in the 20th century. While still a student in Breslau and Leipzig, Ehrlich became interested in dyes and their effects on living tissue. His cousin Carl Weigert (1845-1905) taught him the technique of staining bacteria. Weigert was not the first to use colored compounds as biological stains; before Weigert used methyl violet to stain bacteria in animal tissues in 1875, chromic acid, magenta, and hematoxylin were used for the same purpose. The purpose practice has a history of more than 10 years. Various staining methods were rapidly developed among bacteriologists and histologists. R. Koch (Rober Koch (1843-1910) used the reaction of bacteria to dyes as a tool to identify different bacteria. H. C. J. Gram introduced the identification technique he used in 1884. Many other scientists made made further contributions.
Based on the selectivity of some specific dyes for certain bacteria or certain tissues, Ehrlich came to the insight that it should be possible to use the appropriate dyes to treat diseases. He demonstrated in 1887 that methylene blue could color living nerve cells without affecting adjacent tissue, and that it could color some bacteria without affecting others. Can some dye be found that can attach to a specific organism and kill it without damaging the cells of the host organism?
In 1889 Ehrlich became a member of Robert Koch's Institute for Infectious Diseases in Berlin. In 1892, when Emil Von Behring (1854-1917) discovered the antitoxin to treat diphtheria, he had already established a close relationship with Emil Von Behring. Ehrlich has a lot to do with the development of serum. He later became director of the National Serum Institute in Frankfurt am Main. Although he was busy all day with serum production and experiments, he continued to work hard to find a dye that was both highly specific for pathogens and relatively non-toxic to higher animals.
He obtained the cooperation of Casile Chemical Factory, which provided him with samples of some new compounds produced in their laboratory. In addition, thanks to the establishment of Georg Speyer-Haus in 1906, he was able to surround himself with a group of assistants, chemists and bacteriologists, to synthesize and modify compounds, and to study Effects and effects of these compounds on pathogens and animals. At an early stage Ehrlich proposed his theory of side chains with bactericidal effects. Based on this theory, it should be possible to design a molecule with side chains that has a complementary effect on a certain parasitic bacteria. The molecule is attached to microorganisms using side chains. May hinder microbial activity or may kill microorganisms. Since these side chains will only act on pathogenic organisms without harming host cells, it would be feasible to design these effective magic bullets. His ideas were partly influenced by the success of serum therapy. Here the pathogen itself stimulates the formation of particularly active substances that kill the pathogen without harming most host cells. Since it was impossible to create many effective serums to treat many diseases, it was necessary to develop chemotherapy and create compounds with specific effects that killed parasitic bacteria.
Because a chemical that is toxic to one organism is almost certainly toxic to other cells, Ehrlich proposed the therapeutic index as a standard to ensure the safety of chemical use. , this index is essentially the ratio of the highest dose that the host animal can tolerate to the effective therapeutic dose. As early as the early 20th century Ehrlich and Shiga (Qing Dynasty). (Jie) discovered that trypanosoma red is particularly effective in treating diseases caused by trypanosomatids. F.E.P. Mesnil and M. Nicolle proved that the efficacy of trypan blue is even higher. These drugs have had some success in treating some tropical diseases such as sleeping sickness and equine trypanosomiasis. In 1906 Koch used para-aminophenylarsine to treat diseases caused by trypanosomatids in humans. This compound was prepared by Bechamp in 1863 and is believed to be the anilide of arsenic acid. In 1905, Liverpool doctors H.W. Thomas and A. Breinl announced in their report that the compound had the effect of poisoning trypanosomatids; therefore, p-aminophenylarsine (Atoxyl's non-toxic) was used. A name because it is not toxic to the host. Ehrlich knew that arsenic and nitrogen were in the same group of elements in the periodic table, so he was extremely interested in arsenic compounds; he confirmed that the compound had an effect on trypanosomatids, but found that it could not be used because it was too toxic and would damage Optic nerve. He expressed doubts about the chemical structure of p-aminophenylarsine prepared by Bechan and proposed the correct structure of the compound. Because he had extensive practical experience with dyes, he also proposed that a free amino group would appear in the structure.
Around this time, Treponema pallidum, the organism that causes syphilis, was discovered by E. Hoffmann and Fritz Schaudinn. Schaudin noted that the organism, a spirochete, had more of a protozoan character than a bacterium. Ehrlich designed new arsenic compounds that could be tested on rabbits and mice suffering from these diseases. Starting from the fact that the azo group is a therapeutic unit in dyes such as trypan red, he used reasoning to postulate that trivalent arsenic may be more effective than pentavalent arsenic, as found in p-aminophenylarsine . His chemist A. Bertheim prepared these compounds; asastin (paraacetamidophenylarsonic acid) was found to be particularly effective in experiments against trypanosomiasis. Compound No. 418, arsenylglycine, proved to be more effective. More compounds were synthesized in the laboratory and tested under the direction of his Japanese assistant, Sahachiro Hata. In 1909, Compound No. 606 was successfully used to treat syphilis. The drug was later marketed as salfosan or arsophenamine. Later, in 1912, a more convenient compound 914, New Salfosan, was developed. Treatments using these arsenic preparations were soon introduced.
Although the new Salvosan was not without its shortcomings, it remained the standard treatment for syphilis until the 1940s, when effective antibiotics were not available to treat the disease. The success of arsenic-containing preparations as effective drugs gave people a feeling of great optimism. It is thought that the chemical industry could manufacture a similar variety of chemotherapeutic agents. However, all enthusiasm turned into disappointment. Because the research results on those compounds that are effective do not allow people to know how to synthesize various molecules so that they are specific for certain diseases without being harmful to the host. With the exception of Bayer 205 and a few other compounds, there was little real success in developing chemotherapeutic agents between 1910 and 1930.
Bayer 205, also known as Germanin, was adopted as a specific drug for the treatment of African sleeping sickness in 1920. German Bayer (the company's American branch was seized during World War I and forced to become an independent company) obtained these drugs while they were severely restricted, and was accused of Medicines have been used as a political weapon to help Germany regain its lost colonies. Ernest Fourneau (1872-1949) of the Pasteur Institut (Pasteur Insti-tute), even though he had not obtained the patent rights and Bayer refused to provide drugs for his research, he still put it into use. compounds were identified. A group of scientists, together with the British Dyestuff Company, also played an active role in solving the above difficult problems. By reviewing pre-war German patent literature, Forno learned that they had conducted extensive research on complex urea derivatives. There is further evidence in these published patent documents that there is now considerable interest in the aminobenzoyl and naphthylamine benzene sulfonic acid end groups bonded by some amides, as is the interest in trypanosome dyes. After a test analysis eliminated hundreds of possible compounds, the field was narrowed down to 25, and each compound was subjected to synthetic and biological and chemical experiments. One of them, Forno 309, was confirmed to have the trypanocidal ability of Bayer 205, without being toxic and chemically stable. Comparison with 56 mg of the German product that the Pasteur Institute managed to obtain proved that the two compounds were identical, and the Germans refused to admit that the two compounds were identical; Forno 309 was patented in the UK and the US , this compound has a significant effect on early-stage sleeping sickness, but has no effect on late-stage sleeping sickness. In 1919, W.A. Jacobs (Walter Abraham Jacobs) and M. Heidelberger (Michael Heidelberger) of the Rockefeller Institute of Medical Research confirmed the efficacy of trypanosome arsenamine on advanced sleeping sickness affecting the central nervous system.