Abstract: Objective:Prepare Lianbu sustained-release gel, to examine its basic physicochemical properties, degree of release and toxicological properties, and to evaluate its pharmacodynamic effects in the treatment of experimental periodontitis. Methods:The prescription process for the preparation of Lianbu sustained-release gel was optimized by alkaline phosphatase assay to obtain the optimal mass ratio of the extract of coptis and the extract of rhizome drynariae. Glycerol, glyceryl triacetate, hydroxyethyl cellulose and polyacrylic acid resin were used as gel matrix to prepare Lianbu sustained-release gel with 2%, 4%, and 6% drug-loading rate, and their morphology, pH, stability, and the release rate in vitro were examined to optimize the optimal amount of drug loading. Acute toxicity test in mice at 20 g/kg by gavage using the maximum tolerated dose method. The mucosa of the lower lip of SD rats was sutured into a blind pouch, and then the sustained-release gel was injected into the pouch and applied to their lower gingival mucosa for local mucosal irritation experiments. Long-term toxicology experiments were conducted in SD rats by continuous gavage for 90 days to examine the blood routine and histopathological indexes. An experimental periodontitis model was established in SD rats, and the three-dimensional morphology of the alveolar bone of rats was observed using micro-CT, and the CEJ-ABC was measured. Results:The optimum mass ratio for the preparation of coptis extract and rhizome drynariae extract was 1∶10. The 2%, 4%, and 6% Lianbu sustained-release gel all had good injectability, were in the neutral pH range, and were well stabilized. 6% Lianbu sustained-release gel had the best effect on release. No acute toxic side effects were seen in mice given the sustained-release gel. The mucous membrane contact test did not show any significant irritant reactions such as erythema and edema. Long-term toxicology experiments showed no difference in general activity status, behavioral activities, diet, urine and stool, weight gain, hematology of rats in the Lianbu sustained-release gel group compared with the control group, and no obvious pathological changes were seen in the pathological examination of organs, indicating that the drug had no obvious toxic side effects. After treating experimental periodontitis rats for 4 weeks, micro-CT imaging results showed the alveolar bone resorption was significantly improved in 6% gel group and CEJ-ABC was significantly less than that in blank gel group and control group（P<0.05）. Conclusions:The prepared 6% Lianbu sustained-release gel had excellent physicochemical properties and slow-release performance, and had certain therapeutic effects on experimental periodontitis rats.