"For researchers, developing a major new drug is like a long marathon. Whoever runs to the end and wins will have to go through many great tests, but I didn't expect the advent of Ginkgo Diterpenoid Glucosamine Injection to be so difficult. " Xiao Wei, chairman of Kangyuan Pharmaceutical Co., Ltd. and director of the State Key Laboratory of New Technology of Chinese Medicine, who is in charge of the project, told the story behind his winning the gold medal in patent.
Break through the bottleneck of innovation and overcome technical difficulties
Studies have shown that antagonizing platelet activating factor receptor (PAFR) is a new way to treat ischemic stroke. Diterpenoid lactones in Ginkgo biloba leaves have always been considered as powerful natural PAFR antagonists. Since the 1990s, in-depth research and new drug development have been carried out worldwide, but none of the drugs have been successfully listed. At the same time, China is the main producing area of Ginkgo biloba leaves, but most of the drugs listed at present are crude extracts of Ginkgo biloba leaves, and the original medicinal materials and extracts are mainly exported. Due to the low technical content, this resource has not been fully utilized.
Seeing the technical blank in this field, Xiao Wei thinks it is a rare opportunity, which is not only related to the quality of life of a large number of ischemic stroke patients, but also related to the innovation and progress of modern Chinese medicine. Therefore, Xiao Wei led his team to start a long road of research and development of ginkgo diterpenoid lactones.
To seize the opportunity, we must first meet the challenge. At that time, Kangyuan Pharmaceutical had just completed the restructuring, with weak scientific research conditions, lack of talents and shortage of funds. "We are not 100% sure of success, but we are confident that we will encounter problems and solve them." Xiao Wei said. When the scientific research conditions are not mature, Kangyuan Pharmaceutical established a research institute to cooperate with external scientific research units; If there is a shortage of talents, hire external experts to form a professional team; If there is a shortage of funds, open source and reduce expenditure, reduce costs and increase efficiency. "Since the goal has been set, even if 10 year, 20 years, 30 years, it will be completed." Xiao Wei said.
In fact, the research and development of ginkgo diterpenoid lactone drugs is much more difficult than expected. There are many homologues of ginkgo diterpenoid lactone, and the pharmacodynamics of each component and how to cooperate with each other are still unclear. In the early stage, the R&D team repeatedly prepared ginkgo diterpenoid lactone compositions with different proportions by using Ginkgo biloba leaves from different sources, and then found the best proportion range of ginkgo diterpenoid lactones A, B and K through a large number of experiments.
The content of ginkgo diterpenoid lactone in ginkgo biloba leaves is only about one thousandth, so it is very difficult to purify it. In order to overcome this technical problem, the laboratory was brightly lit for more than three months. Xiao Wei and his team survived countless sleepless nights and experienced numerous setbacks. After repeated trials and failures, they finally invented a new process route of water extraction, adsorption, elution and recrystallization, and removed the components unrelated to PAFR. If there is a problem, it will solve the problem; When another problem appears, continue to solve it, and in this way, push the work of R&D forward step by step.
Over the years, Kangyuan Pharmaceutical Co., Ltd. has completed the development of an innovative Chinese medicine-Ginkgo Diterpenoid Glucosamine Injection through systematic basic research and multi-center clinical effectiveness and safety research. In 2002, the company submitted a patent application for related technology and was authorized in 2006.
Don't forget that your active thinking mission is to make effective use of it.
In 20 12, the patented ginkgo diterpenoid glucosamine injection obtained the new drug certificate, becoming the first innovative drug developed and marketed with PAFR as the target in the world. But there is no end to innovation. Xiao Wei and his R&D team have not stopped the pace of innovative research and development, and continue to work hard for the effective use of innovative drugs.
Based on the fingerprint quality control method in this award-winning patent, they established the whole process fingerprint standard of patented products to ensure the quality stability of medicinal materials, raw materials and preparations. At the same time, they deeply analyzed the transfer law of core components in each process link and process point, established a quality control system for the whole production process, and built an intelligent manufacturing technology group of Chinese patent medicines integrating advanced equipment, automation control, process analysis, information management, data mining and other technologies, and successfully practiced it in large-scale production to achieve drug quality consistency. On the other hand, on the basis of this core patent, Xiao Wei and his team continued to carry out in-depth research and development, including the optimization of the proportion of active ingredients, detection methods, new dosage forms and new indications. And submitted 56 invention patent applications one after another, forming a strict patent layout.
Realizing that the cost of treating patients with severe ischemic stroke often becomes a heavy burden for the whole family, Kangyuan Pharmaceutical Co., Ltd., led by Xiao Wei, took the initiative to assume more social responsibilities. As early as 20 17, the price of ginkgo diterpenoid glucosamine injection was reduced by about 35%, and it was declared to the relevant departments to enter the 20 17 national medical insurance catalogue to serve the clinical needs of the public. 20 19 is the seventh year of Ginkgo Diterpenoid Glucosamine Injection. The drug has been clinically applied in more than 600 secondary and tertiary hospitals in more than 240 cities across the country, bringing good news to thousands of patients in Qian Qian and enabling them to recover from the pain of stroke.
"I especially like Ginkgo biloba leaves, because it records the long and arduous years of scientific research, creates the tenacity in Kangyuan people's bones, and also achieves the birth of this breakthrough innovative medicine ..." Xiao Wei's words are still full of enthusiasm and unremitting pursuit of innovation. (CoCo WU)