Tu Youyou has been engaged in the research of integrated traditional Chinese and western medicine for many years, and his outstanding contribution is to create new antimalarial drugs artemisinin and dihydroartemisinin. A colorless crystal with the molecular formula of C 15H22O5 was successfully extracted from 1972 and named artemisinin. 20 1 1 In September, artemisinin, a drug used to treat malaria, saved millions of lives around the world, especially in developing countries, and won the Lasker Prize and the "Outstanding Achievement Award in Life Science" of GlaxoSmithKline China R&D Center. 20 15- 10 Tu Youyou won the nobel prize in physiology or medicine for discovering artemisinin, which can effectively reduce the mortality of malaria patients. She became the first China person to win the Nobel Prize in Science.
Tu Youyou is the first China native scientist to win the Nobel Prize in Science and the first China scientist to win the Nobel Prize in Physiology and Medicine. [It is by far the highest award in China's medical field, and it is also the highest award for the achievements of traditional Chinese medicine.
Research and development of artemisinin
The first inventor of artemisinin, a new antimalarial drug.
Malaria is a serious worldwide epidemic. Every year, more than 300 million people are infected with malaria in 100 countries around the world. Since the 1960s, original antimalarial drugs such as chloroquine have failed due to the resistance of plasmodium to them. The Vietnam War prompted the international search for new antimalarial drugs. At home ("523" organized seven provinces and cities to screen more than 3,200 kinds of Chinese herbal medicines, and some people gave up the homemade Artemisia annua because it was ineffective) and abroad (the United States screened 300,000 kinds of compounds to meet the needs of the invasion war), under the guidance of modern science, it inherited and carried forward the medical heritage of the motherland, led the research group to systematically sort out medical books and materia medica in past dynasties, and collected more than 2,000 kinds of prescriptions. After the development of more than 380 samples, especially combined with ancient drug use experience, from the Eastern Jin Dynasty? Ge Hong's "Elbow Backup Emergency Prescription" records that Artemisia annua is used to "wring juice" to stop malaria. Considering the temperature, enzymolysis and other factors, the extraction method was continuously improved, and finally the anti-malaria excavation of Artemisia annua was successfully realized in 197 1 year.
The effective fraction and monomer artemisinin found have 100% antimalarial effects on mouse malaria and monkey malaria. After a lot of drug extraction, safety experiments and self-administration, the effective fraction and artemisinin monomer were first studied in Changjiang malaria area of Hainan Province on 1972 and 1973 respectively, which proved that its curative effect was better than chloroquine, and a new antimalarial drug-artemisinin was born.
Tu Youyou and others began to study the chemical structure of artemisinin after separating artemisinin monomer from 1972, and successively cooperated with Institute of Organic Science of Chinese Academy of Sciences and Institute of Biophysics, and finally determined the three-dimensional structure of artemisinin by X-ray diffraction. Artemisinin is a new sesquiterpene lactone with peroxy group, and it is also a new antimalarial drug with completely different structure from previous antimalarial drugs, which breaks the previous assertion that antimalarial drugs must contain nitrogen heterocycles. Therefore, the discovery of artemisinin not only found a new drug to solve the problem of malaria resistance, but also opened up a new way to find new antimalarial drugs. Through national cooperation, more than 2,000 cases have been verified, and it has been confirmed as a new antimalarial drug with high efficiency, quick effect and low toxicity, especially for chloroquine falciparum malaria.
Discovered dihydroartemisinin
Discovery of dihydroartemisinin for the first time
When studying the chemical structure of artemisinin, Tu Youyou pioneered its reducing derivative-dihydroartemisinin in 1973. This is of great significance in the research of artemisinin drugs:
(1) Confirmed the existence of carbonyl group in artemisinin structure; (2) Various artemisinin derivatives can be prepared by using hydroxyl groups in dihydroartemisinin structure, which can enhance efficiency, expand biological activity, promote the research on artemisinin drugs at home and abroad, and make better contributions to human health care; (3) After seven years' efforts, the scientific research team led by Tu Youyou has created a new generation of antimalarial drugs with clinical efficacy 10 times higher than artemisinin and recurrence rate as low as 1.95%. Its tablets have more outstanding advantages such as "high efficiency, quick response, safety, small dosage, convenient oral administration, low recurrence rate and simple preparation", especially confirmed by pharmacodynamics and clinical research. The drug was awarded the National Certificate of First Class New Drugs (92 Wei Yao Certificate X-66,67)1992. It has been produced in large quantities and distributed in the international market, and has a good response. It is considered as "an ideal oral therapeutic drug for treating various types of malaria in the world".
Study Artemisia annua
Complete the "variety arrangement and quality study of Artemisia annua"
Tu Youyou at the 20 1 1 annual "Lasker Award" ceremony.
During the "Seventh Five-Year Plan" period, he participated in the national key project "Variety Arrangement and Quality Research of Common Chinese Medicinal Materials", systematically studied Artemisia annua, and isolated and identified 17 compounds, five of which were new compounds, which corrected the fallacy of long-term use in China Pharmacopoeia.
In order to prevent the emergence of artemisinin resistance, protect the clinical service life of artemisinin and avoid abuse, the effect of dihydroartemisinin on the development of plasmodium yoelii in mosquitoes was studied in cooperation with Capital Medical University. It was found that artemisinin affected the gametophyte infectivity of Plasmodium yoelii, but did not inhibit the sporozoite proliferation period in mosquitoes, that is, it failed to inhibit the oocysts from continuing to develop into sporozoites. It is suggested that artemisinin drugs should not be used for malaria prevention.
1978 after the artemisinin appraisal meeting, the work of the scientific research group in charge of Tu Youyou continued to deepen, and artemisinin obtained the first new drug certificate (No.86-X-01) after the implementation of the new drug examination and approval measures by the Ministry of Health 1985. 198 1 year, at the request of who, the international conference on artemisinin was held in Beijing. Tu Youyou was the first to give a report on "Chemical Research of Artemisinin", which was highly praised. He believes that "the discovery of artemisinin not only adds a new antimalarial drug, but also the unique chemical structure of this new compound will point out the direction for the synthesis and design of new drugs." This has made new progress in international anti-malaria work, and also prompted many countries in the world to further study artemisinin.
Compound dihydroArtemisia annua
A compound dihydroartemisinin composed of artemisinin and acridine antimalarial drugs was developed.
In order to solve the global spread of multidrug-resistant falciparum malaria, foreign countries have attached great importance to the research of compound drugs in recent years. Dihydroartemisinin is the first choice of artemisinin drugs at present, and there is no cross-resistance to multidrug-resistant falciparum malaria. However, the acridine antimalarial drug-pyronaridine has no cross-resistance with 4-aminoquinoline, pyrimidine, guanidine and sulfonamides. Therefore, a compound composed of dihydroartemisinin and pyronaridine was designed. With the support of the Academy of Military Sciences, experimental studies have confirmed that the two drugs have significant synergistic effect, with a synergistic index of 7.6 (higher than that of the compound artemether composed of artemether and benflumetol, which is widely used at present, with a synergistic index of 6), and many action sites and a short course of treatment. The two drugs were combined to treat falciparum malaria 10 cases, and were taken twice within 12-24 hours to achieve high efficiency, and no protozoa reappeared for 40 days. Has obtained the patent certificate (patent number: ZL 99 109669. x)。
Dihydroartemisinin suppository
According to WHO data, about 3,000 babies and children die of malaria every day. Therefore, dihydroartemisinin suppository was developed to promote rectal administration in children. However, artemisinin directly obtained from Artemisia annua is made into oral tablets, which is simple to make, low in price and not easy to produce drug resistance. In 2003, they all obtained new drug certificates, namely, Chinese medicine certificates H2003034 1 and H20030 144.
Extended efficacy
It is found that dihydroartemisinin has a good two-way regulatory effect in the field of immunity, which can not only reduce the hyperreactivity of B cells to reduce autoimmune diseases caused by the deposition of immune complexes, but also improve the immune function of T cells. With the support of relevant departments of Beijing Medical University, we use dihydroartemisinin to treat lupus erythematosus and photosensitive diseases. At present, it has been approved by the US Food and Drug Administration as "Drug Clinical Research Approval Number" (2004L02089) and China Invention Patent (PatentNo.: ZL 99 103346.9). According to the preliminary observation of clinical curative effect of 100 cases, the total effective rate is 94% and the remarkable effective rate is 44%.