| 1. Aim:To observe the analgesic, anti inflammatory and auricular micro circulation effect of Tonglingshuan in different animal and the clinical efficacy and adverse effects on carcinomatous pain patients for the purpose of finding a new analgesic drug finally approved by the SDA for a novel drug.2. Materials and methods(1)Objects: Include an animal experiment and a clinical trial; the former was using Kunming strain, ICR mice, Wister and SD rat for the experimental object the clinical trial was carried out from Jan. 1994 to Mar. 1995 including 70 admitted patient at Department of Oncology, Zhejiang Chinese tranditionalHospital. All of the patients had histology proved diagnosis , and suffered with carcinomatous pain. The patients were divided randomly into a Tonglingshuan group and a indomethacin group. (2) Methods1) Experimental study: including 3 parts: analgesic experiment: The analgesic effects was observed in mice using body-torsion methods and temperature stimulation methods; the relationship between the route of administration and the analgesic effects was also observed in Wistar rats using temperature stimulation methods.Anti-inflammatory experiment: The inflammation of mice was induced by dimethyl benzene and the inflammation of toes in rats was induced by carrageenan. The study of auricular microcirculation in mice influenced by Tonglingshuan as a noradrenergic antagonist was carried out by observing the diameter of the blood vessel the vascular loop and the microvascular blood flow rate, and r.b.c. aggregation.2) Clinical trial: The 70 patients with carcinomatous pain were divided randomly into Tonglingshuan group and indomethacin control group using the index in verbal rating scale ( VRS ) methods (the chief complain about the change of severity of pain) and visual analogue scale (VAS) methods (line segment grading methods) for the evaluation of analgesic effects. In addition, the initial time of pain relieving and persistence of the analgesic action, the analgesic efficacy for osseous metastatic pain induced by tumours, the adverse effects and the appraisal of the 2 drugs stated by patients were also observed at the same time. 3. Resultsã‘esults of experimental study:Analgesic experiment : The 3 groups of Tonglingshuan with different dosage experiment using temperature stimulationmethods revealed that the 3 Tonglingshuan groups with different dosage all had evident analgesic effects started at 10 minutes after the administration and reached the high peak at 20-30 minutes and then began to decline after 40 minutes showing an evident time-effect relationship. The analgesic efficacy of Tonglingshuan of large dose group (lOg/kg) was slightly better than that of the indomethacin group (20mg/kg), the analgesic effects of Tonglingshuan group with medium and small dosage (5g.kg, 2.5g/kg) and that of indomethacin group (20mg/kg) had no significant difference within 30 min. (P>0.05). But the analgesic effects of Tonglingshuan group was lower than that of indomethacin group after 30 min. (P<0.05). The analgesic effects of Tonglingshuan group with different dosage and indomethacin group were all lower than that of the morphine (dosage) group (P<0.001). A comparison of the routes of administration in the Tonglingshuan group showed that gastric perfusion had a slowerinitial time but with longer persistence and rectal route faster initiation of pain relieving with shorter persistence. (P<0.05). The dose-effect relationship analysis of Tonglingshuan revealed that a significant dose-effect relationship was noted at the time 20min following rectal perfusion (r=0.996, P<0.01).(2) Anti inflammatory experiment: Tonglingshuan with different dose all had a notable inhibiting action on the inflammation induced with dimethylbenzene in mice: (P<0.01). IN Inflammation induced by carrageenan 2hr after administration only indomethacin had anti inflammatory action. But from the 3rd hr, indomethacin group and Tonglingshuan of Large and median dose group (lOg/kg, 5g/...
|
PDF Full Text Request