Rapid establishment of traditional Chinese medicine prevention and treatment of 2019-nCoV based on clinical experience and molecular docking / 中国中药杂志

The coronavirus disease 2019(COVID-19) is raging in China and more than 20 other countries and regions since the middle of December 2019. Currently, there is no specific drug or vaccine besides symptomatic supportive therapy. Taking full advantage of the clinical experience of traditional Chinese medicine(TCM) in preventing and controlling major epidemics such as SARS, it is an important mission for TCM to propose effective formula with immediate response and solid evidence by using modern biomedical knowledge and techniques(molecular docking assisted TCM formulation for short). In view of the high homology between the gene sequences of the novel coronavirus and SARS virus, and the similarities between the two in terms of pathogenic mechanism and clinical manifestations, our team established a rapid screening and optimization model for the prevention and treatment of the novel coronavirus based on clinical experience and molecular docking technology. Firstly, the clinical team and the research team pre-developed and screened TCM formula by using "back-to-back" manner. Then, the formula was optimized and determined by comparing and analyzing the results of the two groups. The results showed that the research team screened out 46 active ingredients from candidate TCMs that could act on the novel coronavirus S-protein-binding site of human ACE2 protein, which were mainly attributed to 7 herbs such as Lonicerae Japonicae Flos and Mori Folium. The result was largely consistent with the formula raised by the clinical group, verifying and supporting its rationality. This provides evidence for the scientific and potential efficacy of the TCM prescription from the perspective of treatment target analysis, and also suggests that the TCM prescription has the potential to directly inhibit viral infection in addition to improving clinical symptoms or syndromes. Based on this, our team optimized and formed a new anti-coronavirus TCM prescription "Keguan Yihao", immediately providing the TCM prescription with certain clinical experience and objective evidence support for the prevention and treatment of new emergent infectious diseases in our hospital. The TCM prescription was combined with modern medicine symptomatic supportive treatment for clinical treatment, preliminary results showed better effect than symptomatic supportive therapy alone. This research has innovated the method mode in clinical practice and basic research integration of traditional Chinese medicine for the prevention and control of new emerging infectious diseases. It is of great significance to further improve the rapid response mechanism of TCM in face of major epidemics, and further improve the capability level of TCM to prevent and treat new emerging infectious diseases.

Formula Optimization of Bromhexine Hydrochloride Dry Powder Inhalations by Central Composite Design-response Surface Methodology / 中国药师

Objective: To optimize the formula of bromhexine hydrochloride dry powder inhalations (BH DPIs). Methods: BH DPIs were prepared by freezing-drying combined with an air-jet milling method. Three factors, including the weights of mannitol (X1), leucine (X2) and poloxamer 188 (X3) in the formula were known to be associated with the quality of BH DPIs. A central composite design was used to investigate the effects of the three factors on the response angle (Y1), fine particle fraction (FPF, Y3) and aerody-namic diameter (Y4). Response surface and overlay contour plot were delineated according to the best-fit mathematic models. Opti-mum formula was selected by overlay contour plot. Results: The quantitative relationships between the three factors and the three re-sponses were obtained. The optimal formula was mannitol﹕leucine﹕poloxamer 188 (2. 4: 2. 22: 0. 05) in the excipients. The pre-dicted and observed values of the optimum formula were similar. Conclusion: The multi-objective simultaneous optimization of the for-mula of BH DPIs is achieved by central composite design-response surface methodology.

Formula Screening and in vitro Drug Release of Tegafur Thermo-sensitive Gel for Intratumor Injection / 中国药师

Objective:To screen the best formula of tegafur temperature-sensitive gel for intratumor injection and investigate the in vitro drug release behavior. Methods:The drug dose was determined by cytotoxicity experiment. The thermo-sensitive gel was prepared with PLGA-PEG-PLGA and HPMC as the matrix. With the in vitro release as the index, the effects of PLGA-PEG-PLGA and HPMC at different concentrations on gel were investigated. The gelation temperature, viscosity and pH were detected. Results:The best formula was as follows:25% PLGA-PEG-PLGA, 1% HPMC, and tegafur dose of 1 mg·ml-1 . The average gelation temperature was 36. 7℃, the average viscosity was 7550 mPa·s, and the average pH was 7. 2. Conclusion:Tegafur thermo-sensitive gel for intratumor in-jection shows temperature sensitivity and obvious sustained-release property, which provides experimental basis for the further clinical research.

Formulation Screening of Insulin Cream and Its Effects on Skin Injury in Model Rabbits / 中国药房

OBJECTIVE:To screen formulation of Insulin cream and to investigate the effects of insulin cream on wound healing in rabbits.METHODS:The best formulation of insulin cream was selected from 8 kinds of formulations with appearance and stability as index.Rabbit trauma model were induced and divided into matrix group,blank group,Insulin cream groups(high-dose,medium-dose and low-dose).Wound healing rate and healing time were compared among those groups.RESULTS:The fifth formulation possessed good appearance and stability,which included albolene,cetanol,glycerin monostearate,glycerol,etc.Compared with matrix group,the wound healing rates were obviously increased at different time points in Insulin cream groups(P