People's understanding of C- 14 (carbon 14, the radioactive isotope of carbon) may still be stuck in the archaeological carbon dating of cultural relics. I remember when I was a child, I used to watch archaeology programs that often mentioned C- 14 dating. In fact, in addition to archaeological dating, C- 14 has been widely used in the fields of medical treatment, agriculture, chemical industry and environmental protection.

However, for a long time, China's C- 14 raw materials and intermediates are heavily dependent on imports, which is extremely unfavorable to the development of isotope technology and its application industry in China. There is one such company in Wuxi, Jiangsu. They have spent nearly ten years developing C- 14 key intermediate compounds, trying to break the foreign monopoly on the C- 14 industry chain through their own technology research and development, so that China can have its own C- 14 industry chain and labeled products. This company is Wuxi Beta Pharmaceutical Technology Co., Ltd.

Research and development of C- 14 intermediates, breaking the monopoly of foreign technology

In the process of isotope labeled synthesis, the key is the production of labeled intermediates. Labeled intermediates are mainly raw materials in the production of subsequent compounds, such as formic acid, acetic acid, benzoic acid, cyanide, etc. In the process of synthesizing isotope-labeled compounds, C- 12 in these intermediate compounds need to be replaced by C- 14 through various chemical reactions, and then the C- 14-labeled intermediates are used to synthesize the final target compounds, so that the final target compounds are labeled with C- 14 isotopes.

Domestic isotope labeled intermediates have long been heavily dependent on imports. The R & D team of Beta Pharmaceuticals explored the production technology of these labeled intermediates one by one, hoping to break the monopoly of C- 14 intermediates by foreign countries.

During this period, Beta Pharmaceuticals received strong support from a number of national science and technology talent project funds, such as Wuxi "530" Talent Plan, Jiangyin Science and Technology support Plan, Jiangsu Science and Technology support Plan, and the Innovation Fund of the Ministry of Science and Technology. Beta Pharmaceuticals eventually lived up to expectations and successfully synthesized dozens of commonly used key intermediate compounds. The technological breakthrough made by Beta Pharmaceuticals has brought the production of C- 14 isotope-labeled compounds in China one step closer to being completely domestic.

C- 14 is widely used in healthcare industry

In medical treatment, C- 14 main application directions are radioisotope tracing and Helicobacter pylori infection detection.

"Low-energy radioisotopes (such as C- 14, H-3) labeled compounds should be used in pharmacokinetic studies. Because of their low biological background value, they are easy and sensitive to detect, and have a long half-life without the need to correct the test results according to the radioactive half-life. Metabolites produced by candidate drugs can be quantitatively analyzed without guiding their structures, and the energy of non-ionized β-rays produced is very low without special protection, it has been proved to be a safe and effective special technology. The results are simple, clear and reliable. At present, there is no other replacement method in most cases." This description is not my hearsay, but from the "Technical Guidelines for Non-clinical Pharmacokinetics of Drugs" issued by the former State Food and Drug Administration.

The C- 14 is used for radioisotope tracing, which is equivalent to installing a navigation system on the target molecule for location tracking. The chemical properties of the compounds synthesized by C- 14 are almost no different from the original compounds. Radioisotope tracer has three advantages: high sensitivity, simple detection method and accurate positioning and quantification.

Radioactive tracer method has extremely high sensitivity, which can be measured to the level of 10-14-10-18g, I .e. one radioactive atom can be detected from 1015 non-radioactive atoms, which is more sensitive than gravimetric analysis balance. When radioactivity is used for tracing in vivo, it will not be interfered by other non-radioactive substances, and the results can be obtained through in vitro measurement, which is extremely convenient for detection. As the content of radioisotopes in nature is extremely low, therefore, the detection of radioisotopes is hardly interfered by background factors, and accurate positioning and quantification can be performed.

Helicobacter pylori infection detection is closer to daily life. The C- 13 or C- 14 urea breath test detection system is currently recognized as the gold standard for H. pylori detection. After a period of oral administration of the capsule, the subject blows into the expiratory bag. In the capsule taken by the subject is a C- 13 or C- 14 labeled urea molecule. If H. pylori is present in the stomach, the labeled urea molecules are broken down and CO2 is produced. C- 13 or C- 14 labeled CO2 can eventually be detected in the gas collected in the breath bag.

C- 13 is one of the stable isotopes of carbon, a naturally occurring isotope of carbon. C- 13 is not radioactive and contains about 1.11 percent of the carbon in nature. C- 13 raw materials are therefore produced mainly by mining from nature. The production of C- 13 raw material 13CO needs to be selected in areas with very stable geological conditions, and the rectification separation is carried out in a distillation tower up to 200 meters high, which is very difficult to produce.

At present, the main suppliers of C- 13 raw materials in the world are in the United States, and the annual output is limited. Even if all the C- 13 are used to produce detection reagents for Helicobacter pylori every year, it can only meet the detection needs of about 20 million people per year. Compared with C- 13, the amount of C- 14 used for detection is much smaller. 1 gram of C- 14 labeled urea can meet the detection needs of nearly a million people. And because the amount used in the test is very small, the effect of C- 14 radioactivity on the human body is almost negligible. Eating a C- 14 urea capsule for breath test is only equivalent to eating ten bananas.

Therefore, the need for detection of H. pylori infection worldwide can only be met by relying on C- 14.

Based on isotope labeling, continue to expand the scope of business.

Beta Pharmaceuticals currently has a 2400-square-meter special laboratory building for C- 14 and H-3 marking in Jiangyin High-tech Zone, Wuxi City; in addition, there is a 1500-square-meter special laboratory for C- 13, N-15 and H-2 marking in Changsha. Since its inception, Beta Pharmaceuticals has received 16 patents for inventions and developed hundreds of precursor compounds labeled with multiple isotopes. In March 2019, Science and Technology Daily reported on the results of Beta Medicine and published it simultaneously on the "Learning Power" platform.

In April 2014, Beta Pharmaceuticals received round A financing from Shanghai Kaiyuan Investment. In the first half of 2019, a new round of financing of about 10 million yuan was completed.

2018 is of great significance for Beta Pharmaceuticals, which has been established for ten years. In early 2018, Beta Pharma's C- 14 isotope labeling officially provided services to the outside world, and reached cooperative relationships with leading domestic new drug development pharmaceutical companies such as Haosen Pharmaceuticals, Hengrui Pharmaceuticals, Koren Pharmaceuticals, Nanjing Shenghe Pharmaceuticals, Beijing Sailintai, Fujian Haixi Pharmaceuticals, etc., and successfully achieved profitability.

In addition to its existing business, Beta Pharmaceuticals is actively expanding its own business areas. Beta Pharmaceuticals is currently planning the development of a diagnostic kit for gastric Helicobacter pylori, which will be sold directly to the C- side in the future. Recently, the document issued by the Ministry of Ecology and Environment has brought new development opportunities for Beta Medicine.

In January 2019, the Ministry of Ecology and Environment issued the Regulations on Environmental Impact Assessment and Control of Chemical Substances (Draft for Comment). This draft for soliciting opinions is mainly aimed at enterprises engaged in the production, processing, use, import and export of chemical substances in China, requiring enterprises to assess, prevent, control and supervise the environmental risks of chemical substances.

As the world's largest producer of chemicals, the tightening of regulatory policies on chemical substances is bound to bring a large market that can be developed. The high sensitivity and accurate positioning of C- 14 isotope markers are suitable for in-depth assessment of the impact of chemicals on the environment.

A communiqué of the United Nations Atomic Energy Agency pointed out: "In terms of the breadth of application, only modern electronics and information technology can be compared with isotopes. Isotope technology is making valuable contributions to the development of the world's society and economy." For beta medicine, the past ten years have been a decade of hard work and hard work. It has realized the leap from import to domestic production of C- 14 key intermediate compounds, laying a solid foundation for the next step of development.

The next ten years will be a decade of taking advantage of the situation and accelerating development. Although Beta Pharmaceuticals has now begun to fully carry out the industrialization of isotope labeling such as C- 14, and has achieved profitability, it is far from being able to stop. In the next decade, Beta Pharmaceuticals will continue to focus on isotope technology and its applications, so that more isotope-labeled compounds and labeling services can be imported instead of domestically, so that isotope technology can benefit China and the world.