Preliminary evaluation of the efficacy and safety of brimonidine for general anesthesia.

BACKGROUND: To determine the hypnotic and analgesic effects of brimonidine, and evaluate its efficacy and safety for general anesthesia. Potentiation of pentobarbital sleeping time following brimonidine administration was observed in mice, as was the analgesic activity of brimonidine. METHODS: The median effective dose (ED50) and lethal dose (LD50) of intraperitoneally injected brimonidine were determined in hypnotized mice. In addition, the LD50 of intravenously injected brimonidine, and ED50 of intravenously, intramuscularly, and intrarectally injected brimonidine in hypnotized rabbits were determined. Finally, the synergistic anesthetic effect of brimonidine and chloral hydrate was evaluated in rabbits. RESULTS: Intraperitoneal injection of 10 mg/kg brimonidine enhanced the hypnotic effect of a threshold dose of pentobarbital. Intraperitoneally injected brimonidine produced dose-related analgesic effects in mice. The ED50 of intraperitoneally administered brimonidine in hypnotized mice was 75.7 mg/kg and the LD50 was 379 mg/kg. ED50 values of intravenous, intramuscular, and intrarectal brimonidine for hypnosis in rabbits were 5.2 mg/kg, 8.8 mg/kg, and 8.7 mg/kg, respectively; the LD50 of intravenous brimonidine was 146 mg/kg. Combined intravenous administration of 0.6 mg/kg brimonidine and 0.03 g/kg chloral hydrate had a synergistic anesthetic effect. CONCLUSIONS: Brimonidine elicited hypnotic and analgesic effects after systemic administration and exhibited safety. Moreover, brimonidine enhanced the effects of other types of narcotics when combined.

Biosafety evaluation of medical injectable carboxymethyl glycosaminoglycan gel / 国际生物医学工程杂志

Objective:To evaluate the biosafety of medical injectable carboxymethyl glycosaminoglycan gel.Methods:Ames test, chromosome aberration test in vitro and gene mutation test in vitro were used to detect the genotoxicity of the medical carboxymethyl glycosaminoglycan gel. The gel saline extract (50 ml/kg) was injected slowly through the marginal vein of the ear into Japanese big-eared rabbits. The body temperature was measured and the temperature rise was calculated. The gel saline extract (50 ml/kg) and normal saline (control) were injected intraperitoneally and intravenously into the Kunming mice, respectively. The toxicity response in mice was observed after injection, and bodyweight change was valued. The gel saline extract, normal saline and distilled water were added into the rabbit anti-clotting, to detect the rate of hemolysis.Results:Under active and inactive conditions, the number of spontaneous revertants of the 4 strains of gel saline extract group and gel DMSO extract group did not reach 2 times of that of the corresponding negative control group. The rate of chromosome aberration of the three dose groups were 0. There was no significant increase in the large colony mutation frequency, small colony mutation frequency and total mutation frequency in three dose groups (all P>0.05). After injection of gel saline extract for 24, 48 and 72 h, no toxic reaction was found in each group of mice. With the extension of time after injection, the body weight of mice in the sample group and the control group increased, but the difference was not statistically significant ( P>0.05). After injection of gel saline extract, the temperature rise of 3 Japanese big-eared rabbits were 0.0, 0.3 and 0.2 ℃ respectively. The results of hemolysis test showed that the hemolysis rate of the polycarboxymethyl glucosamine gel was 0.1%. Conclusions:No genetic toxicity changes were found in carboxymethyl glycosaminoglycan to induce gene mutation or chromosome damage in bacteria and cells, and no pyrogenicity, acute systemic toxicity and hemolysis were observed. These results indicate that thecarboxymethyl glycosaminoglycan gel has good biosafety.

Biosafety of medical injectable carboxymethyl glycosaminoglycan anti-adhesion gel / 中国组织工程研究

BACKGROUND: The injectable carboxymethyl glycosaminoglycan anti-adhesion gel prepared in the previous study combines the advantages of anti-adhesion membrane and anti-adhesion liquid. It can form soft gel in situ in a relatively short time, which is not affected by body position, bear the pressure of surrounding tissues and can be used without compression. OBJECTIVE: To evaluate the biocompatibility of medical injectable carboxymethyl glycosaminoglycan anti-adhesion gel. METHODS: Logarithmic growing L929 cells were used as test cells, and the cytotoxicity of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract was detected by MTT method. The intradermal stimulation test of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract was carried out in Japanese big ear rabbits. Guinea pigs were used as experimental animals to carry out intradermal induction and local induced delayed hypersensitivity test of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract. Wistar rats were used as experimental animals to carry out the subchronic toxicity test of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract. RESULTS AND CONCLUSION: The cytotoxicity of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract was grade 1, meeting the standard requirements. Injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract had no potential intradermal stimulation and no potential skin sensitization. In the subchronic toxicity test, the rats were subjected to the tail vein injection of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract for 28 continuous days, and there was no obvious subchronic systemic toxicity in body mass, hematology, coagulation function, blood biochemistry and visceral pathology. These results indicate that the injectable carboxymethyl glycosaminoglycan anti-adhesion gel has good biosafety.

Synthesis and biosafety evaluation of four acryl acetyl glucosamine with cell membrane binding ability / 国际生物医学工程杂志

Objective To synthesize and characterize four acryl acetyl glucosamine (DA-NAG), and to determine its biocompatibility and cell membrane binding properties, so as to provide basis for its application in medical self agglutination gels. Methods DA-NAG was synthesized by esterification reaction. The products were characterized by mass spectrometry and hydrogen spectrum. Cytotoxicity test and subcutaneous implantation test were performed on the synthesized DA-NAG. The binding properties of DA-NAG to mouse fibroblast L929 cell membrane were detected using high performance liquid chromatography (HPLC). Results The characterization of mass spectrum and hydrogen spectrum are consistent with the characteristics of DA-NAG. The product has no cytotoxicity, and the subcutaneous implantation shows that the DA-NAG can be degraded at 4 weeks without obvious stimulation to the surrounding tissues. The result of HPLC shows the binding effect between the DA-NAG and cell membrane. Conclusions DA-NAG is successfully synthesized, and it has good cytocompatibility and binding ability to cell membrane.