Pulai medicine: the first antibacterial peptide in clinical research in China, which focuses on high-efficiency and low toxicity and side effects

Author: the resistance of Jiao Yanli's pathogenic microorganisms to traditional antibiotics has become a more and more serious problem It is an increasingly urgent task to develop new drugs that can inhibit or kill pathogenic microorganisms Antibacterial peptide has the advantages of fast sterilization, broad antibacterial spectrum, small side effects and no immunogenicity Moreover, due to its special bactericidal mechanism, the inhibited or killed pathogenic microorganisms will not produce resistant strains, and will not weaken the bactericidal effect due to drug resistance Therefore, antimicrobial peptide drugs have become an ideal alternative to antibiotics, and have attracted a lot of attention in the medical field At present, peptide antibacterial drugs on the market include Brevibacterium peptide, polymyxin, etc Chen Yuxin, chairman of Pulai pharmaceutical, said: "the bactericidal effect of antimicrobial peptides on the market is not enough, and the toxicity of digestive tract and kidney is strong, side effects are large, so the use is very limited." Pulai pharmaceutical is committed to the research and development of new generation of antimicrobial peptide drugs, using the "cell membrane differentiation mechanism" of antimicrobial peptides, peptide solid-phase synthesis technology, and redesigning the sequence of antimicrobial peptides, so that the antibacterial effect of antimicrobial peptide drugs is better and the side effects are lower At present, the company has 4 antimicrobial peptide drugs in clinical stage Among them, pl-5 is the first innovative antimicrobial peptide in clinical research in China, which has entered clinical stage II, and is suitable for open wound stubborn infectious diseases caused by resistant bacteria and sensitive bacteria Antimicrobial peptide is an ideal substitute for antibiotics, Chen Yuxin said: "since the 1970s, antibiotics without new structure and new mechanism have been successfully developed, but bacterial resistance has become stronger and stronger, and the world has fallen into a" drug shortage "of anti infective drugs." It is understood that more than 700000 people die of antibiotic resistant infection every year in the world, and it is expected to reach 10 million people every year by 2050 Who has regarded antibiotic resistance as "one of the biggest threats to global health, food safety and development", and China has also released the national action plan to curb bacterial resistance (2016-2020) The threat of antibiotic resistance is becoming more and more serious It is one of the most urgent medical problems to study new anti infective drugs Antimicrobial peptides have broad-spectrum antibacterial activity, the target strains are not easy to produce resistant mutations, and have a strong killing effect on bacteria (including some resistant pathogens) It is believed that antimicrobial peptides are expected to become an ideal alternative to antibiotics Chen Yuxin has many years of experience in the research and development of antimicrobial peptides He studied in Canada for a doctorate in biochemistry, and later went to the University of Colorado School of medicine to pursue postdoctoral studies In the United States, Chen Yuxin first proposed the "cell membrane differentiation mechanism" of antimicrobial peptides, and developed his first patented product pl-5 In 2007, Chen Yuxin returned to China with his patent In 2009, he founded Jiangsu Pulai pharmaceutical In our country, about 75% of outpatient cold patients use antibiotics, and 95% of surgical patients use antibiotics According to the survey of the World Health Organization, the utilization rate of antibiotics in inpatients in China is as high as 80%, among which 58% use more than two kinds of antibiotics in combination, far higher than the international level of 30% According to incomplete statistics, 10 of the top 15 drugs in consumption and sales are antibiotics It is because of the fact that China is a big country of antibiotic abuse that Chen Yuxin chose to go back to China and start his own business to benefit more domestic patients In 2014, Pulai began to apply for the clinical approval of pl-5, waiting in line for approval Fortunately, by the end of 2015, the state issued a number of policies to encourage pharmaceutical innovation, and the speed of drug approval was significantly accelerated In 2016, Pulai pharmaceutical obtained phase I, II and III clinical approval documents at one time, saving a lot of time Chen Yuxin said: "Pulai medicine has caught up with a good era of innovative medicine development." In addition, the national action plan to curb bacterial drug resistance (2016-2020) clearly points out to increase the research and development of antibacterial drugs and support the research and development of new anti infective drugs The antibacterial peptide project of Pulai medicine has obtained the support of government departments at all levels, and has been listed in the "science and technology innovation fund for small and medium-sized enterprises" project of the Ministry of science and technology and the health and Family Planning Commission, as well as the major new drug development projects of the 12th five year plan and the 13th five year plan Master the exclusive design technology of antimicrobial peptides, anti infection innovative drugs have entered phase II clinical practice According to Chen Yuxin, Pulai pharmaceutical has mastered the effective design method of antimicrobial peptides The company's antimicrobial peptide drugs are all new antimicrobial peptide molecules obtained by the application of peptide head-on design technology Through the modification of the hydrophobicity, amphiphilicity and helicity of antimicrobial peptides, their toxicity to human body has been reduced Pratt & lyk has established a strong R & D team led by Nobel Prize winner Dr Michel and academician Dr Hawkins of the Royal Academy of Sciences of Canada, with Michel biomedical (Jiangyin) Research Institute and Robert (Jiangyin) foreign academician workstation The company has designed a number of new antibacterial peptide varieties and applied for related patent protection At present, the company has a number of R & D pipelines, including antibacterial peptide varieties pl-5, pl-18 and pl-33, anticancer peptide varieties pl-ac and so on PL-5 sprays are the 1 class of innovative anti infective drugs in the country They are the first innovative antibacterial drugs in clinical research in China They are suitable for infectious diseases of skin and wounds, especially for refractory infectious diseases caused by drug-resistant bacteria They aim at the "super bacteria" Pseudomonas aeruginosa with strong antibiotic resistance, methicillin resistant Staphylococcus aureus (MRSA) and NDM- 1 gene multiple resistance Acinetobacter baumannii has a very strong sterilization advantage Phase I and II a clinical studies of PL-5 sprays have been completed and phase II B clinical studies are under way "Phase III clinical trials are expected in 2020," Chen said Pl-18 suppository has a good killing effect on bacteria and fungi Its sequence has been authorized by PCT, USA, EU and China It is understood that this kind of suppository is to be developed as a vaginal suppository, which is suitable for gynecological infection caused by bacteria and fungi, especially for stubborn infectious diseases caused by drug-resistant bacteria At present, preclinical research is under way Pl-33 eye drops have good stability It is proposed to be developed as ophthalmic preparation, which can be used in various bacterial and Mycoplasma Chlamydia induced ocular infectious diseases At present, the project is under research Pl-ac injection under Pulai pharmaceutical is a national class 1 innovative new anti-tumor drug and has applied for a Chinese invention patent This variety has good broad-spectrum antitumor activity It has good antitumor activity for more than ten common clinical tumors It is planned to be developed as an injection At present, the design and synthesis of compounds and the screening of in vitro activity have been completed, and the preclinical research work is in progress There are three ways of administration of antimicrobial peptide: external use, oral administration and injection At present, the main antimicrobial peptide varieties of Pulai medicine are for external use "In the experiment, we found that there was a strong binding between antimicrobial peptide and plasma albumin, and it was not released after binding, so the local lesions need to have a certain concentration of antimicrobial peptide to produce efficacy," Chen said In order to solve this problem, Pulai pharmaceutical is carrying out peptide sequence transformation to improve the application prospects of peptides in vivo, and developing new antibacterial peptide varieties that can be injected and orally as soon as possible It has been about 40 years since the establishment of the world's leading antimicrobial peptide pharmaceutical enterprise with equal emphasis on R & D and production However, there has not been any blockbuster drug yet Chen Yuxin said: "it's hard to imagine the R & D cycle and technical difficulty of antimicrobial peptide drugs It is hoped that more people will recognize the importance of antimicrobial peptide drugs, support or invest in the research and development of antimicrobial peptide drugs " Pulai medicine, which has been in the field of antimicrobial peptide medicine for more than 10 years, has become the leader in this field Since its establishment, Pulai pharmaceutical has obtained more than 10 PCT international invention patents, Chinese invention patents, American invention patents and European Union invention patents, and has undertaken more than 30 scientific and technological projects including the 12th Five Year Plan and the 13th five year plan "major new drug creation" In 2009, the company was awarded the first batch of "key overseas Chinese enterprise team" by the overseas Chinese office of the State Council; in 2014, it was awarded as "China's most potential seed enterprise" by Ernst & young, one of the world's largest accounting firms At the same time, Pulai pharmaceutical has also won the favor of many investment institutions Tianyan inspection shows that the company has completed three rounds of financing, including state investment and entrepreneurship, gingko Valley capital, Jincai investment, etc Considering the long research and development cycle of new drugs and large capital investment, the company has developed a number of single molecule antibacterial peptide killing products, which have been listed and sold in the country, with an annual sales volume of up to 10 million, and can provide financial support for the company's new drug research and development projects Pulai medicine firmly believes that antimicrobial peptide is an effective way to inhibit bacterial resistant bacteria In the future, based on the series of antibacterial peptide products, Pulai pharmaceutical will maintain the advantages of both R & D and production, expand the market with high-quality innovative products, and strive to become the leader of international antibacterial peptide pharmaceutical enterprises On September 20, 2019, the first phase project of Pulai pharmaceutical industry base has been officially opened Chen Yuxin revealed that in 2020, the company will build a new R & D center in Nanjing After completion, the R & D strength of the company will be further enhanced, and the R & D pipeline will be promoted rapidly Chen hopes that pl-5 will be available in two to three years Jeni turtle