Artemisinin is the first antimalarial drug developed by China in the world. It is an effective monomer separated from Artemisia annua, a folk medicine for malaria treatment in China. Its research began in the mid-1960s. Under the personal instruction of Premier Zhou, hundreds of scientists have made unremitting and in-depth research. It is one of the few new drugs independently developed by scientists in China and registered internationally. It was evaluated by the World Health Organization as the only truly effective drug for the treatment of falciparum malaria. At the 10th International Chemotherapy Conference held in Istanbul, 6,000 medical experts from all over the world recognized artemisinin as a Chinese magic medicine for treating malaria, which was an autopsy in the world medical history and a great contribution to mankind. At present, the World Health Organization has provided funds for verification and promotion.
Because artemisinin is insoluble in water, its solubility in oil is very small, and its dosage form is only suppository, so its bioavailability is low, which affects its efficacy. Since the mid-1980s, China has developed artemisinin derivatives and compounds. China has successfully developed artesunate, artemether and dihydroartemisinin. Artesunate and artemether can be taken orally and injected, and dihydroartemisinin can be taken orally and suppository. Anti-malaria compound has also been developed, including compound dihydroartemisinin and compound artemether. At present, there are dihydroartemisinin preparation, artesunate preparation, artemether preparation and compound artemether on the market.
Second, the pharmacological characteristics of artemisinin drugs
According to the action link and practical application of antimalarial drugs on the life history of plasmodium, it can be divided into three categories:
A. Anti-malarial drugs, such as ethambutol, act on the outer phase of primary cells and are mainly used for prevention;
B antimalarial drugs that act on red blood cells and are mainly used to control symptoms, such as chloroquine, quinine, pyronaridine, artemisinin, etc. ;
C. antimalarial drugs, such as primaquine, act on the outer phase of secondary cells, which are mainly used to control recurrence and spread. Artemisinin drugs are mainly used to control malaria symptoms and have little effect on preventing recurrence. Through pharmacological and clinical research, artemisinin drugs have been widely recognized in the world, with strong anti-plasmodium activity and special curative effect on falciparum malaria. They can kill plasmodium in erythrocytic stage, but have no effect on infrared stage and secondary infrared stage. Its antimalarial mechanism is also unique, which mainly acts on the membrane structure of trophozoites, changes the food capsule membrane, mitochondrial membrane, nuclear membrane and endoplasmic reticulum, and finally leads to the structural cracking of worms.
They have great advantages in controlling malaria symptoms and treating cerebral malaria and chloroquine-resistant plasmodium falciparum malaria. Its disadvantage is high recurrence rate, but the recurrence rate also decreases with the extension of treatment time. Taking dihydroartemisinin as an example, the recurrence rates are 3 days 52, 5 days 5 and 7 days 2.
Third, the resource status of green storage elements.
Artemisinin is mainly extracted directly from Artemisia annua; Or extract Artemisia annua from Artemisia annua, and semi-synthesize. The total synthesis process is complex and the cost is too high; Tissue culture is immature because of the input-output ratio of technology and practical application. At present, no other natural plant resources containing artemisinin have been found except Artemisia annua. Although Artemisia annua is a widely distributed variety in the world, the scenery of Artemisia annua from different habitats is very different. According to the research results so far, the artemisinin content in Artemisia annua produced in most parts of the world is very low, and it has no use value except in eastern Chongqing, Fujian, Guangxi and Hainan. According to the investigation of relevant state departments, at present, only artemisinin grown in Wumu Mountain in Youyang, China has industrial refining value. For this unique drug resource, the relevant ministries and commissions of the country have banned the export of artemisinin's original plants (Artemisia annua), seeds, dried and fresh whole grass and artemisinin raw materials since the 1980s. In the research and development of artemisinin, only powerful China enterprises are encouraged to participate. Therefore, China has obvious advantages in resources and research and development.
Four, malaria and its incidence at home and abroad.
Malaria is the most prevalent tropical parasitic infectious disease with the highest morbidity and mortality in the world. According to the statistics of the United Nations World Health Organization in recent years, the global malaria area is distributed in 1. According to incomplete statistics, there are more than 400-500 million clinical patients living in malaria areas, and 2-3 million people die every year. Africa, Southeast Asia and Latin America are the most serious. The areas with high incidence of malaria are mainly in sub-Saharan African tropical countries. Many foreigners who go to Africa for business and tourism are also susceptible to malaria. Therefore, Africa is the largest market for antimalarial drugs in the world at present, and about half of its total pharmaceutical trade is used to import antimalarial koji and related items. At present, the global annual sales of antimalarial drugs is as high as $654.38+0.5 billion.
Malaria is also widely distributed in China, among which malaria is the most common, covering the whole country; Plasmodium falciparum is the second, mainly distributed in the south; Three-day malaria is scattered in the southern mountainous areas; Oval malaria is rare. From north to south, the prevalence is getting more and more serious. For example, Guizhou province is known as the hometown of boils, and the incidence of malaria in Yunnan, Guangxi, Guangdong and Hainan provinces is also very high. Before the founding of New China, there were more than 30 million malaria patients in China every year. After liberation, due to the vigorous development of prevention and control work, the incidence of malaria in most areas has been greatly reduced, and the annual incidence has dropped from 1954 122.6 to1990/000. Malaria is very rare in some big cities. However, with the continuation and deepening of China's reform and opening up, foreign exchanges have become increasingly extensive, tourism has developed, and the number of people entering and leaving the country has increased sharply. Large-scale population movements have created favorable conditions for the spread and spread of malaria. For example, according to relevant data, there were only 7 malaria patients in Shenzhen in 1 979. With the construction and development of the special zone, a large number of floating population poured in from various provinces and regions, and the poor living conditions on the construction site led to the rapid spread of malaria. By 1984, there were 7427 malaria patients in the city, and the malaria carrier rate of healthy people was as high as 10.3. According to the statistics of Shanghai Institute of Parasitic Disease Prevention and Control, malaria in Shanghai suburbs has been basically controlled. 1987 ~ 199 1 year, the number of people suffering from malaria in this area is 196, and the annual incidence rate is 0.44 ~1.04/100000. During the same period, there were 6 13 migrants suffering from malaria, which was three times that of local people. The sampling survey of foreign population shows that the insect-carrying rate is as high as 0.82.
Generally speaking, the current market for antimalarial drugs is mainly abroad, especially in Africa. Although the incidence of malaria in China is on the rise, the market is still small.
Verb (abbreviation of verb) Market prospect of Huang Qing capsule medicine
At present, because there are more than 9o malaria cases in the world on the African continent, more than 90 African countries rely on imported drugs. Chloroquine products (mainly quinine and chloroquine) account for 80% of the world antimalarial drug market. At present, the treatment cost of these products is relatively high, and the whole course of treatment is about $65,438 +0.5 ~ 2 days, with great side effects. At the same time, due to the emergence of plasmodium falciparum strains, plasmodium has developed drug resistance (especially in Southeast Asia, the drug-resistant plasmodium strains have reached 8O), so it can be said that these drugs have basically failed, which has brought difficulties to malaria prevention and control. Therefore, it is urgent to find new antimalarial drugs.
Artemisinin drugs have great advantages in resisting chloroquine-resistant Plasmodium falciparum malaria. As Goda, head of the tropical infectious diseases agency of the World Health Organization, said, artemisinin derivatives are new drugs for malaria. Experts predict that these drugs will replace traditional antimalarial drugs such as quinine and chloroquine at a very fast speed and become the mainstream drugs in the future, accounting for 30 ~ 50% of the world antimalarial drug market. Artemisinin industry is attracting worldwide attention and becoming an industry with great market prospects. As a special industry, the life cycle of pharmaceutical products is obviously longer than that of general industrial products, especially the market introduction period of products. Generally, the introduction period of a brand-new drug takes 5 ~ 10 years. Artemisinin in China is in the market introduction period. It has not yet entered a period of rapid growth.
Six, China's strong support for Artemisia annua industry.
From a national point of view, the significance of internationalization of artemisinin industry is not limited to the potential market value of about 654.38 billion US dollars per year. More importantly, artemisinin is one of the few drugs with independent intellectual property rights in China, and its position in the international medicine field plays an important role in promoting other medical products in China, especially traditional Chinese medicine. The aid led by artemisinin industry may promote the rapid development of internationalization of traditional Chinese medicine, thus forming a new economic growth point of China pharmaceutical industry. From applied research, wormwood planting, raw material extraction to the production and sales of artemisinin preparations, China is beginning to promote the industrialization of artemisinin and support the artemisinin industry to form a complete industrial chain.
According to the current situation of artemisinin industry, the state gives centralized financial support. With the modern enterprise system, a large-scale enterprise with cross-regional, cross-ownership, transnational and cross-disciplinary raw materials, products, markets and scientific research will be established. Through industrialization, the quality and output of raw materials will be improved, the production cost will be greatly reduced, and the international competitiveness of artemisinin industry in China will be rapidly enhanced. After the efficacy of artemisinin drugs is made public to the world, it is unrealistic to keep competitive advantage by blocking the export of natural resources such as raw materials or seeds. The only way to participate in the international competition of artemisinin drugs is to innovate and protect its intellectual property rights by applying for patents to ensure its competitive advantage in the international market. Some experts suggest that joint-stock companies should be set up in China to research, develop, produce and sell new drugs, make a commission from profits, conduct new drug research or other innovative research, and transform the chemical structure in order to achieve sustainable development. In this process, only by organically combining the scientific research achievements of scientists with the business strategies of entrepreneurs can we move forward more smoothly.
Seven, China management errors of artemisinin drugs.
Although China has obvious advantages in resources and R&D of artemisinin industry, the marketing power of domestic pharmaceutical companies is limited, and the market development strategy has gone through a detour. The export of pharmaceutical products in China has always been dominated by raw materials, and the trade mode is "existing demand" general trade. Artemisinin products are initiated by scientists in China, so we need to create demand in the target market first. Domestic enterprises are lacking in international marketing ability, talents, capital and experience.
At present, the global annual sales of antimalarial drugs is as high as $654.38+0.5 billion, but it is mainly monopolized by pharmaceutical companies in western countries. Although China is at the world leading level in the research and development of antimalarial drugs, due to historical reasons, China's artemisinin industry has not yet formed a reasonable industrial structure. Artemisinin raw materials, products, market ability and scientific research ability are scattered in different regions, which is not conducive to the formation of scale advantages, and the industrial competitiveness of the park is greatly reduced. At present, the export of artemisinin products produced in China in the international market is less than 7 million dollars, accounting for less than 3.
Since 1980s, western pharmaceutical companies have been fighting for the market control of the above products through agency and acquisition. Now, all varieties of artemisinin have transferred the right to open up foreign markets to western pharmaceutical companies. At the same time, these drugs are copied by many western countries because they have no patent protection, and they are forced to occupy the market first. At present, the main producing countries are Viet Nam, French and Swiss besides China. The research results of China scientists have become a cash cow for foreign pharmaceutical companies. The development of artemisinin in the past 20 years has once again confirmed an ironclad fact: the success of products does not mean the success of the market.
Taking the analysis of Kunming Pharmaceutical by Guotai Junan Securities Research Institute as an example, the company's artemether series includes raw materials, injections, tablets, capsules and compounds, mainly injections and tablets. The company has the right to import and export independently, and their annual export value of artemether products reaches more than 3 million dollars. Judging from the sales of the company's main products in the past three years, the sales investment of artemether series has increased steadily year by year. Compound artemether tablets A+B jointly developed by the company and Novartis were listed on 1 999. The company owns intellectual property rights, and Novartis is responsible for international market sales. Raw materials A and B required for the product are provided by the company. The company now supplies 0.5 tons of Novartis artemether every year. The company raised funds to expand the production of artemether API, which increased the production capacity of artemether API from 1 ton to 2.5 tons, and will produce 2 tons of Novartis every year. This is equivalent to transferring the production and sales rights of major markets to Novartis, and the company mainly benefits from the sales of raw materials. Because the company's sales ability in the international market is weak, there is no way to cooperate in this way.
Eight, the prospect of artemisinin drugs.
Since the target market of artemisinin drugs is mainly abroad, our competitors are mainly leading western pharmaceutical companies. This requires us to have strong export capacity. With the maturity of China Enterprise 13, some enterprises (such as Kunming Pharmaceutical Factory) have started to set up their own business offices in Africa, and increased their efforts to develop the African market. After joining the WTO, our exports will be in a more favorable position.
In terms of technology, domestic enterprises have also increased their development efforts, such as developing compound preparations, continuing to look for new derivatives and expanding new indications. Chongqing Tonghe Pharmaceutical Company successfully developed dihydroartemisinin compound preparation. Some scientific research institutions have studied derivatives of artemisinin to treat tumors, leishmaniasis, lupus erythematosus and other diseases, and at the same time began to explore new uses of artemisinin in the treatment of AIDS, malignant tumors, leishmaniasis, schistosomiasis, tapeworms, Toxoplasma gondii and other diseases and detoxification.
As long as we make full use of China's advantages in artemisinin drug resources and scientific research, increase scientific research and market development, supplemented by strong support from national policies, artemisinin industry will certainly become a new economic growth point for China's pharmaceutical industry.