Reporter Li Nannan Correspondent Qi Jiansheng Sun Yan
Recently, based on the integrated platform of "science, industry, education" integration platform of Yantai University and Green Leaf Pharmaceuticals, the national Class 1 innovative drug - Torudivenlafaxine hydrochloride sustained release tablets (trade name: Ruoxinlin®), developed by the scientific research team of the Key Laboratory of Molecular Pharmacology and Drug Evaluation of Yantai University, was approved for marketing by the National Drug Administration.
has been in 12 years from research and development to its approval for marketing. This drug is China's first innovative drug for chemical drugs to treat depression and has independent intellectual property rights. Its launch has achieved a major innovative breakthrough in domestic drugs in the field of treatment, marking that my country is heading to the forefront of the world in the field of innovative drug development of CNS ( central nervous system ) with high failure rate.
Twelve years of hard work
A new drug has a hard time urging
"Approved! Approved!" On November 3, Ruoxinlin® was approved for marketing. "The moment the leader told me, I was very excited and couldn't help but be excited." said Zhong Yan, project manager of the R&D project management department of Green Leaf Pharmaceutical Group.
This excitement comes from the persistence and efforts of day and night, and has finally been recognized. Zhong Yan participated in this project throughout the whole process. After 12 years, he knew the difficulties. "Overtime is common. At 10 o'clock in the evening, the laboratory lights are still on. We have to compete with many competitors for speed and rush."
National Class 1 innovative drug - Torudivenlafaxine hydrochloride sustained release tablets. Photo by reporter Li Nannan
Ruoxinlin® R&D work is fully hosted by Professor Tian Jingwei, Vice President of the Non-clinical Research Department of Green Leaf Pharmacy and Drug Evaluation, Head of the New Drug Discovery Research Department, Yantai University School of Pharmacy Professor Fu Fenghua, Wang Hongbo, Liu Wanhui, Sun Kaoxiang and other professors as backbone members of the team, and more than 500 professionals participated. After 12 years of continuous research and development, a technical system of "Research and Evaluation of Multi-target Imbalance Regulation Effect Mechanism" and "Research and Evaluation of Biased Regulation Mechanism" was gradually built, and a conquering study was conducted on the defects of front-line antidepressant drugs, and finally completed the research and development of this national Class 1 innovative drug.
"WHO data shows that about 3.8% of the world's population suffers from depression, which has become an important factor affecting family life and social productivity. Depression treatment has been developed for half a century, but traditional therapeutic drugs in the past still have the defect of "a low cure rate, residual symptoms after treatment, and the patient's function cannot achieve comprehensive recovery." Tian Jingwei said, so 12 years ago, he and his team were determined to try to develop a more effective new drug.
Professor Tian Jingwei of Yantai University (right) guides students in the laboratory. Although
was approved for listing, Tian Jingwei is still busy. On November 14, when the reporter saw him, he was about to go on a business trip to Shanghai. There was a cold lunch box on the table. He was busy and had not had a meal for a day. "I forgot when I get busy." Tian Jingwei said with a smile, "I have lost more than 10 kilograms recently. I guess I can still lose weight when I get another new drug development. Work is the best way to lose weight."
new drug development is full of challenges and difficulties. Tian Jingwei introduced that there are two main difficulties.
"First, what we do is to act on the three targets of serotonin (5-HT), norepinephrine (NE), and dopamine (DA) transporter at the same time." Regarding the relationship between drugs and targets, Tian Jingwei is compared to the relationship between "key and lock". "For our specific drug, this key needs to be able to open three locks at the same time, and there are specific requirements for the opening range of each lock. We have proposed the treatment theory of "unbalanced inhibition of 5-HT, NE, and DA re-uptake". This is a difficulty in global research and development, and it is also the main reason for the failure of most similar drugs."
"Second, 'is the correlation between drug-target-clinical efficacy'. Through specific intensity ratios, can unbalanced inhibition of 5-HT, NE, and DA re-uptake achieve clinical transformation? In fact, it is a proof of concept of the theory proposed earlier, which is also a difficulty in global research and development."Tian Jingwei said, "We built a research platform based on 5-HT/NE/DA triple reuptake inhibition, clarifying the relationship between the intensity ratio of uptake inhibition, effectiveness and safety, and successfully achieved proof of concept in the second phase clinical trial, and finally achieved the success of the third phase clinical trial. "
started in 2010 and was approved for marketing on November 3, 2022. From a small molecule to a marketable drug that benefits patients, Tian Jingwei and his team have gone through a 12-year difficult journey.
"The key is persistence. In fact, our new drug development cycle is quite fast, and many drugs have longer development cycles. From the establishment of research and development to the final launch of an innovative new drug, it is like a long march that requires a long trial. "Tian Jingwei said, "There are more than 50 million patients in China who need standardized medication. How to get such a large number of patients to return to their families and society is a social problem. Since we decided to do it, we never thought of giving up because we deeply feel the pain of our patients. As scientific researchers, we must first have a sense of social responsibility, which is the driving force that supports our perseverance. The launch of Ruoxinlin® is expected to improve the current treatment status of the disease and provide strong support for patients to return to their families as soon as possible and integrate into society. "
triple "treat depression"
A new treatment option
Walk into the R&D building of Green Leaf Pharmaceuticals. There is a prominent place in the lobby on the first floor. Congratulations on the approval of the new drug on the market.
"treat depression, refreshing and brightening" promotional sculpture. Reporter Li Nannan Photo
"Most of the existing drugs are 5-HT reuptake inhibitors and 5-HT/NE double reuptake inhibitors. Ruoxin® is a triple reuptake inhibitor (SNDRI), norepinephrine (NE), and dopamine (DA). "Zhong Yan introduced that triple reuptake inhibitors increase intervention on dopamine (DA), which can achieve mutual coordination of therapeutic effects and more comprehensively alleviate the symptoms of in different dimensions of in patients with depression, and at the same time antagonize the side effects caused by the decrease in DA energy caused by the increase in 5-HT levels.
According to reports, although existing antidepressants are generally effective, there are obviously unmet clinical treatment needs: the cure rate is low, and there are still residual symptoms after treatment, mainly including Including anxiety, cognitive impairment, fatigue, and lack of pleasure, it seriously damages social function and significantly accelerates the recurrence of depression; in addition, it is prone to cause adverse reactions such as sexual dysfunction, weight gain, emotional sluggishness, and lethargy.
Ruoxinlin® was approved based on six clinical studies it completed in China, of which the Phase III clinical trial is a multi-center, randomized, double-blind , placebo-controlled study to evaluate the efficacy and safety of this drug in the treatment of depression. The results of this clinical study Shown: The changes in the total score of the Montgomery -Esberg Depression Scale (MADRS) over the 8-week treatment period were significantly better than the baseline of the total score of the 17-item Hamilton Depression Scale (HAM-D17), the changes in the total score of the 17-item Hamilton Depression Scale (HAM-D17), the effective rate of MADRS, the effective rate of HAM-D17, and the changes in the total score of the Hamilton Anxiety Scale (HAM-A) were significantly better than the placebo, especially in improving pleasure loss, block, cognitive impairment and fatigue There are statistical differences in the aspects of labour compared with placebo, and the advantages are obvious compared with traditional antidepressants; Ruoxinlin® is good in safety and tolerance, does not cause drowsiness, and does not affect sexual function, weight and lipid metabolism.
Ruoxinlin® clinical trials, the main investigator of Ruoxinlin® clinical trials, Professor Zhang Hongyan, , Peking University Sixth Hospital, said: "The approval of Ruoxinlin® is a solid step taken by domestic pharmaceutical companies in the development of new antidepressant drugs, and is an important milestone in the history of Chinese psychotropic drug research and development. The clinical pharmacodynamic characteristics shown by Ruoxinlin® help patients to fully alleviate the multi-dimensional symptoms of depression, especially to meet patients' treatment needs for improving anxiety, pleasure loss, fatigue, cognitive symptoms, etc., and provide clinicians with new therapeutic weapons. "
Display of various innovative platforms in the lobby of the first floor of the Green Leaf Pharmaceutical R&D Building. Reporter Li Nannan Photo by
" Depression, as one of the most common mental disorders in my country, brings a heavy burden on patients, their families, and even society.The approval of Ruoxin® has made us excited. The company has prepared commercialization in advance, hoping to take advantage of the advantages we have accumulated in the field of central nervous system therapy to bring this new treatment option to patients as soon as possible and improve the accessibility of innovative drugs. "Yang Rongbing, president of Green Leaf Pharmaceutical Group, said that the central nervous system treatment field, including depression, is one of the core strategic areas of Green Leaf Pharmaceutical. Focusing on this disease field, the company has actively built an innovative product portfolio, improved its own team, went down to channels and expanded the market for many years. It has now promoted the central nervous system products to cover nearly 3,000 hospitals in China, and its commercial advantages are becoming increasingly prominent. Ruoxin®'s approval for listing continues to expand the company's central nervous system product portfolio, further promoting the coordination of the company's existing resources and advantages and deepening of commercial operation capabilities.
university scientific research results transformation
A "from paper to money" transformation of scientific research results, some people call it a process from money to "paper" and then from "paper" to money. The first process is "giving scientific research funds - scientists do scientific research - research results - writing papers and publishing", in which money becomes "paper"; the second process is to transform scientific and technological achievements into core technologies and products, and then push them to the market, and exchange "paper" for money. Only when this cycle is turned can the development of the economy and society be truly promoted.
allows scientific research results to go out of the "wall" of scientific research institutes and transform from paper results to promoting enterprises The real productivity of high-quality development of is a problem facing every scientific research platform. Over the years, Yantai University has closely focused on major development strategies of the country, province and city, and has continuously deepened the integration of schools and local schools and enterprises, and has built a community of collaborative innovation and education between science, industry and education.
2000 Yanda cooperated with Green Leaf Pharmaceutical Group to jointly build the School of Pharmaceuticals of Yantai University, and built a new talent training model of "teachers, schools and enterprises, and students, schools and enterprises". Nearly half of the college's teachers work part-time in the Green Leaf Pharmaceutical R&D Center, responsible for or participate in the research and development of major new drug products for "major new drug creation" led by enterprises, and enterprises deeply participate in the college's professional regulations. The school-running system jointly built by schools and enterprises has incorporated talent training, project cooperation research, and technical achievements transformation into the unified platform, realizing the substantive integration of "science, industry and education".
Yantai University's Key Laboratory of Molecular Pharmacology and Drug Evaluation Ministry of Education.
At present, the research and development of scientific research and development projects participated in by the institute's scientific researchers has filled the gaps at home and abroad. "From early research to the complete process of industrialization and commercialization, it has achieved a seamless bridge between basic research and development and industrialization. "Tian Jingwei said.
Green Leaf Pharmaceutical Group's advanced scientific research conditions and rich industrial practice are integrated with the talent training and scientific and technological research and development of the pharmacy discipline of Yantai University. The school and enterprise jointly create a "source of pharmaceutical innovation", gradually breaking through the technical barriers of new high-end preparations, and creating a world-leading new long-acting preparation technology platform. "Based on the Yanda Pharmaceutical College, we can attract better talents. Through cooperation with some horizontal topics in the school, the efficiency of product development has been improved and the true integration of production, teaching and research has been achieved. This is a win-win situation. "Yu Fei, vice president of the R&D Project Management Department of Green Leaf Pharmaceutical Group, said.
relies on the close integration of industry, academia and research. More than 30 products independently developed by Green Leaf Group cover more than 80 countries and regions around the world. Yantai University's pharmacology and toxicology also entered the top 1% of ESI in the world, and was included in the "first-class discipline" and "strong characteristics" high-level disciplines in Shandong Province. The research team of the School of Pharmaceuticals of
, China's first microsphere preparation product with independent intellectual property rights and global registration, was presided over by the research and development of Green Leaf Pharmaceuticals, risperidone sustained release microsphere preparation for injection, was approved for marketing in 2021. The world's first sustained release microsphere preparation for treatment of Parkinson's disease, has also entered the key clinical research stage of China and the United States.The research and development and marketing of these drugs are of great significance to breaking through the "bottleneck" technology and protecting people's lives and health. It is also a useful exploration of Yantai University to comprehensively deepen the integration of science, industry and education and build a community of collaborative innovation and education.
At present, Yantai University has 34 undergraduate majors implemented the school-enterprise co-construction project, and the school has also established a service Yantai office to accurately match regional development needs. " Yantai City has sorted out 16 key industrial chains . Focusing on the standards of extending chains, replenishing chains, building chains, and strengthening chains, we have matched these 16 key chains one by one to integrate the school-related disciplines, majors and talent strength." said Sun Xutao, director of the Cooperation and Development Department of Yantai University (Serving Yantai Office). At present, the school has signed cooperation agreements with more than 140 companies including Wanhua Chemical , Unigroup and other chain-owned enterprises, and strives to achieve full coverage of Yantai city, county (district) service institutions within 3 years. Starting this year, 100 high-level talents such as doctoral students will be dispatched every year to serve Yantai's economic and social development.
"Actively serving regional economic and social development is the mission of the school and an important way to build a high-level university." Yantai University Party Committee Standing Committee and Vice President Hao Shuguang said that Yantai University will further demonstrate the school-running characteristics of the integration of industry and education in and the integration of science and education, and promote the high-quality development of the school.
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About Ruoxinlin® Toludevinlafaxine Hydrochloride sustained release tablets (trade name: Ruoxinlin®) is a Class 1 innovative drug developed by Green Leaf Pharmaceutical Group based on its new molecular entity/new therapeutic entity technology platform (NCE/NTE). Preclinical research results show that it has the effects of serotonin (5-HT), norepinephrine (NE), and dopamine (DA) triple reuptake inhibition (SNDRI) for the treatment of depression. Clinically, Ruoxinlin® can play a role through the uptake inhibition of a variety of monoamine neurotransmitters . In addition, a Phase III clinical trial for the treatment of generalized anxiety disorders is also underway.
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