Anti Inflammatory Effect Of Inflammatory Pain Ning Capsule And General Toxicology Evaluation

Objective:According to the prescription of Yan Tong Ning capsule and on the basis of certain clinical effect, we did anti-inflammatory experiments and the beagle dog chronic toxicity test of the drug in order to study the effect of anti-inflammation and analgesia, promoting blood circulation and removing blood stasis, the therapeutical effect on rats with collagen induced arthritis(CIA) injury and the drug safety evaluation. Methods:The analgesic effect of Yan Tong Ning Capsule was studied in mice and rats using acetic acid writhing reaction and formaldehyde stimulating voix pedis test.The anti-inflammation effect was studied using the experimental model of mouse ear-edema induced by croton oil, celiac capillary permeability in mice, swelling of rat’s paw induced by carrageenin and rat granuloma. The promoting blood circulation and removing blood stasis effect was observed using the model of blood stasis. The therapeutic effect of Yan Tong Ning Capsule to CIA rat’s paw swelling and local pathological injury of ankle joint was studied by rat’s CIA model. The Yan Tong Ning capsules with 3 doses were continuously administrated to beagle dogs by oral method for 9 months. Then we observed the effect of drugs on the general physical signs, diet, rectal temperature and body weight. We also examined urine, hematology, blood biochemistry, electrocardiogram, department of ophthalmology, etc. Gross necropsy, histopathological and bone marrow were seperately measured after administration of the drug and the recovery time. All of the examinations aimed to evaluate drug’s toxicity. Results:1. Yan Tong Ning capsule has obvious analgesic effect on the pain caused by chemical stimulation, and it can significantly reduce the frequency of licking paw, shaking paw and lifting paw caused by formaldehyde. We find that Yan Tong Ning capsule has obvious analgesic effects except for the pain caused by hyperthermia, so its effect may be mediated by peripheral mechanisms.2. Yan Tong Ning capsule has significant anti-inflammatory effect on the experimental model of mouse ear-edema induced by croton oil, celiac capillary permeability in mice, swelling of rat’s paw induced by carrageenin and rat granuloma, which shows that Yan Tong Ning capsule has significant inhibition on acute and chronic inflammation.3. Yan Tong Ning capsule has significant inhibitory effect on swelling of the ankle of the other side, and can significantly improve secondary lesions of the models’ ears, noses, tails and paws. This shows that Yan Tong Ning capsule has significant therapeutic effect on type II CIA.4. Yan Tong Ning capsule can significantly reduce the proliferation of synovial cells, the hyperemia and edema of synovial tissues, vascular proliferation, the number ofinfiltrating inflammatory cells and the formation of pannus.5. Yan Tong Ning capsule was orally administrated to beagle dogs at the doses of 0.67, 2.0, 6.0 g/kg respectively for 9 months. Compared to the control group, the general observation, body weight, rectal temperature, hematology, serum biochemistry, urine biochemistry, electrocardiogram examination and department of ophthalmology examination of each administration groups show no significant drug toxicity. Gross necropsy, organ weights, histopathological and bone marrow examination at the ending of administration and the recovery time also show no significant drug toxicity. Conclusion:We studied Yan Tong Ning capsule from the aspect of animal experiments and discussed its efficacy and mechanism from multiple perspectives and levels. In observation of the efficacy, we not only observed the effect on inflammatory pain, but also investigated the effect on joint bone destruction. At the aspect of safety evaluation, the long term toxicity test for 9 months in beagle dogs fully exposed the drug’s toxicity, provided the target organ of toxic side effects and its recovery condition, determined the no-toxic-effect dose and provided the reference for clinical safe dose.Yan Tong Ning capsule has significant analgesic and anti-inflammatory effect particularly on inflammatory pain, and there is a certain dose-effect relationship. The analgesic site is in the periphery. It has significant therapeutic effect on CIA rats, can reduce inflammation and tissue injury, decrease the release of inflammatory mediators, reduce local inflammation, improve joint swelling, reduce tissue damage, repair bone destruction. So it has positive significance to recover the body’s physiological function. We can detect the drug’s effect on general observation, diet, body weight, rectal temperature, electrocardiogram, urine, hematology, blood biochemistry, urine biochemistry, gross anatomy and histopathology by the 9 months toxicity test in beagle dogs and evaluate the safety of the drug.The results show that Yan Tong Ning capsule has significant effect of promoting blood circulation, removing blood stasis, anti-inflammation and analgesia. Meanwhile, the pure Chinese herbal preparation can avoid the serious toxicity to the digestive system, endocrine system and bone joint system after injection or oral administration of steroidal or non steroidal anti-inflammatory drugs. Yan Tong Ning capsule nourishes liver and kidney, dispels wind, activates blood and dredges collaterals, and fully plays the role of supporting the healthy energy. These agree with the root cause in treating both the symptoms and root cause.The study provides ideas and methods for promoting and exploring new ways and innovating new drugs in treatment of osteoarthritis.