厦门大学胜泽泰多肽制药工程与智能设备研发中心
Xiamen University & Space Peptides Peptide Pharmaceutical Engineering and Intelligent Equipment R&D Center
2016年，厦门大学化学化工学院与Space Peptides共建“厦门大学- Space Peptides多肽药物产业化研发平台”，由国家高层次人才、厦门大学化学化工学院副院长、福建省闽江学者特聘教授洪文晶教授作为平台负责人，国际著名多肽化学家、厦门大学兼职教授、瑞士伯尔尼大学Jean-Louis Reymond教授担任首席科学家，Space Peptides何润泽博士负责实际运营，主要开展多肽类药物的制药工艺研究和智能反应器研发。
In 2016, college of chemistry and chemical engineering of Xiamen university cooperated with Space Peptides and established ‘Xiamen University and Space Peptides Peptide Drug Industrialization R&D Platform’ that is led by professor Wenjing Hong, a national high-level talent, vice president of school of chemistry and chemical engineering of Xiamen university, and distinguished professor of Minjiang scholars in Fujian province. Professor Jean-Louis Reymond as chief scientist. Dr. Runze He of Space Peptides is responsible for actual operation that is delicate to R&D peptide drug pharmaceutical process research and intelligent reactors.
在校方相关部门的支持下，2020年研发中心升级为校级平台，并更名为“厦门大学胜泽泰多肽制药工程与智能设备研发中心”。中心立足中国制造2025战略规划，依托我校在人工智能、精密仪器开发、拉曼光谱领域的研究基础，结合Space Peptides在多肽制药工艺开发和质量管理体系的经验，共同开展多肽新药研发、自动化多肽制药智能设备和工艺的研发及基于拉曼光谱在线监测智能控制系统的研发。中心将以产出具有创新性、实用性、产业化的技术成果为发展目标，努力促进我国多肽制药产业的发展，为推动我国战略性新兴产业中的生物医药产业和智能制造工程的快速发展做出贡献，并竭力将研发中心建设成为示范型产业化平台。
Under the support of relevant departments of the university, R&D platform has upgraded to field platform whose name is changed to ‘Xiamen University & Space Peptides Peptide Pharmaceutical Engineering and Intelligent Equipment R&D Center’. Based on ‘Made in China 2025’ and our research foundation in the fields of artificial intelligence, precision instrument development and Raman spectroscopy, and in combined with Space Peptides’ peptide pharmaceutical technology development and the experience of the quality management system, we jointly carry out the R&D of new peptide drugs, the R&D of intelligent equipment and process for automatic peptide pharmaceutical and the R&D of online monitoring and intelligent control system based on Raman spectroscopy. The center aims to produce innovative, practical and industrialized technological achievements to promote the development of peptide pharmaceutical industry in China, and to promote the rapid development of biomedical industry and intelligent manufacturing engineering in China's strategic emerging industries, and strive to build the R&D center into a demonstration industrialization platform.
创新研发
Innovative Research and Development
多肽与人工智能
Peptides and artificial intelligence
Jean-Louis Reymond教授创建的Chemical Space大数据已有17年的研究基础，是迄今最大的多肽药物数据库，为基于大数据的人工智能药物发现提供了重要机会。研发中心将基于Chemical Space进行多肽药物设计的机器学习研究，二者的结合应用将大大缩短多肽新药的研发进程。
It has been 17 years since prof. Jean-Louis Reymond found ‘Chemical Space’ big data, which is the largest peptide drug database in the history, and it provides significant chances for artificial intelligence of drug discovery based on big data. The R&D center will conduct machine learning research on peptide drug design based on Chemical Space, and the combination of the two applications will greatly shorten the development process of new peptide drugs.
抗新型冠状病毒感染肺炎的多肽融合抑制剂研发
Development of peptide fusion inhibitors against novel coronavirus infection with pneumonia
新型冠状病毒感染的肺炎是一种急性感染性肺炎，其病原体是一种先前未在人类中发现的新型冠状病毒（2019-nCoV）。根据新型冠状病区表面S蛋白的结构特点，研发中心合作方利用Chemical Space数据库和新药发现理论进行多肽融合抑制剂的设计和结构优化，首批设计的10个多肽分子通过筛选获得了4个具有潜在成药性的多肽化合物序列，并进行了分子动力学模拟验证其靶向结合的作用机制。Space Peptides充分发挥已有的高效绿色多肽合成工艺在短时间内完成了30多个氨基酸序列的首批样品制备，经P3实验室检测，其中一个样品具有明显抗病毒活性。后续，研究中心和瑞方合作者将根据检测结果进行多轮分子优化和样品制备。
A novel coronavirus pneumonia is an acute infectious pneumonia caused by a novel coronavirus (2019-ncov) which isn’t previously known by humans. According to the structure characteristics of new coronary ward S surface protein, research and development center partners using Chemical Space database and the theory of drug discovery polypeptide fusion inhibitors in the design and structure optimization, the design of 10 peptide molecules obtained four through screening potential into medicinal compound peptide sequence, and the molecular dynamics simulation verify its targeted in combination with the mechanism of action. Space Peptides give full play to the existing high efficiency green peptide synthesis technology in a short period of time finished more than 30 amino acid sequence of the first batch of sample preparation, tested by the P3 laboratory, one of the samples has obvious antiviral activity. In the future, the research center and Swiss collaborators will conduct multiple rounds of molecular optimization and sample preparation based on the test results.
抗菌肽-石墨烯外伤凝胶制剂
Antimicrobial peptide - Graphene Trauma Gel Preparation
随着抗生素的滥用，许多细菌产生了很强的耐药性。依托Chemical Space技术开发的抗菌肽具备新型杀菌机理，可有效对抗多重耐药性细菌。而石墨烯水凝胶具有自修复功能，生物相容性较好，且其自身也具有一定的抑菌功能。该项目以厦门大学在石墨烯领域的研究为基础，将石墨烯水凝胶与抗菌肽的结合，开发长效耐久性抗菌肽-石墨烯外伤凝胶制剂，并尝试利用3D打印技术进行制备，可广泛用于医院外伤感染治疗、医院手术伤口恢复以及士兵战场创伤治疗，对我国的公共安全卫生有着重要的意义，也是国家军事战略储备的迫切需要。2019年，研究中心制备的抗菌肽-石墨烯水凝胶样品作为厦门大学产业化项目代表产品参加了中国·海峡项目成果交易会。
With the abuse of antibiotics, many bacteria have developed strong drug resistance. The antimicrobial peptides developed by Chemical Space technology have a novel bactericidal mechanism and can effectively fight against multi-resistant bacteria. On the other hand, graphene hydrogel has the function of self-repair, good biocompatibility, and its own antibacterial function. The project based on the research in the field of graphene of Xiamen university, combine with the graphene hydrogels and the antimicrobial peptide, developing long-term durability of antimicrobial peptide gel preparation - graphene trauma, and try to use 3 D printing technology for the preparation, which can be widely used in hospital, hospital surgical wound recovery and soldiers battlefield trauma treatment. It is significant to our country's public health and safety, also it is also urgent for national military strategic reserve needs. In 2019, the sample of the antibacterial peptide-graphene hydrogel prepared by the research center was selected as the representative product of the industrialization project of Xiamen university to participate in the China · Strait Project Achievement Fair.
多肽药物固相合成工艺开发及优化
Development and optimization of solid phase synthesis of polypeptide drugs
在GMP质量管理体系下，结合Space Peptides现有新型多肽高效合成工艺，进行多肽药物固相合成工艺开发及优化。Space Peptides现已形成具有自主知识产权的新型多肽高效合成工艺，可在短时间内开发多个多肽品种，将40-80步化学反应在短时间内不间断完成。其中多肽药物合成的每步反应收率可高达99.5%，使总产率提高15%。目前已完成小试工艺摸索和中试放大，正在进行公斤级稳定放大实验。本项目后续将结合拉曼光谱全程在线监测，优化工艺参数。
Under the GMP quality management system, combined with the Space Peptides existing highly efficient new peptide synthesis process, polypeptide drugs solid-phase synthesis process development and optimization. Space Peptides has been formed with independent intellectual property rights of new peptide synthesis process efficiently, which could develop multiple peptide varieties in a short period of time and complete it within 40-80 chemical reaction steps. The yield of each step of peptide synthesis can reach to 99.5%, and the total yield can be increased by 15%. At present, the pilot scale and the pilot scale have been completed. In the future, this project will combine with Raman spectrum online monitoring to optimize the process parameters.
智能反应器研发
Intelligent Reactor Development
结合拉曼在线监测技术以及智能控制系统，提高工艺优化的效率和生产过程数据的可追溯性，实现工艺放大过程的在线优化以及生产过程的实时监控优化工艺参数。在国内外连续流液液、气液反应器的基础上，开发适用于多肽固相合成法，且能够完成固液两相高效传质传热的工业生产用连续流设备。目前已经完成多肽连续流合成反应器的固相分离模块的设计和研发，后续将根据实验结果进行再优化。
In order to improve the efficiency of process optimization and traceability of production process data and realize the online optimization of process amplification process and real-time monitoring and optimization of process parameters, we combined with Raman online monitoring technology and intelligent control system. On the basis of continuous flow liquid-liquid and gas-liquid reactors globally, a continuous flow equipment for industrial production is developed, which is suitable for the solid phase synthesis of polypeptides and can complete the efficient mass transfer and heat transfer of solid-liquid two-phase. At present, the design and development of solid phase separation module of the peptide continuous flow synthesis reactor have been completed, which will be further optimized according to the experimental results.
学术成果
Academic Achievements
