| Tribenoside (TBS) was ethyl-3,5,6-tribenzyloxy-D-glucofuranoside and composed of optical isomer α and optical isomer β. It had effect in anti-inflammatory, antitoxin, enhancing the tenacity of micrangium, protecting and curing wound tissue. It was found and synthesized in 1950' s and was developed as oral administration of curing haemorrhoids first in Japan in 1999. Because of its much better liposolubility, TBS was easily absorbed by small intestine and had high availability. So its clinical therapeutic effect was greater than other same kind drugs~[1-4].So far, TBS hadn' t had any domestic reseach reports. TBS which was studied in this article was a new drug made in our courtry by medicine college of Sichuan university and HaiShen pharmacy corporation in Hainan. It was necessary to establish accurate, credible, actual and feasible quality standard to direct the reseach and manufacture of TBS material made in our courtry. According to its property and structure, in this article, there was a penetrating study on its quality control method such as physical-chemical identification, impurity test and determination of content, etc. Then, the quality standard of TBS material had been primarily established.The physical property of TBS, such as solubility, absorption coefficient,hygroscopicity and optical rotation, etc, had been studied in this article. The UV-Vis absorptive spectrum characteristic was studied, and the result was followed: Specific absorptivities (J?!^) was 12.04 at 258nm, its maximum absorption wavelength, in 95% Alcohol. On the point of relative humidity was 92.48%. The optical rotation([ a ]20D) was between -27° and -35° in Chloroform. Indirect iodometry was developed for the assay of reference substances of isomer a and isomer p. Then RP-HPLC was performed for the determination of raw drugs. TBS and its related substance were separated on the Hypersil Cis column (250x4.6mm, lOum) with methanol-water (80:20) as the mobile phase and detected at 258nm. The calibration curves were linear (r =0.9999) within the range of 33.0 ~ 660.8 u g ? ml'1 for isomer a, the detection limit was 0.15 u g (S/N=3), the analysis precision RSD was less than 1.0% (?=5), the repeatability precision RSD was 0.51% (h=6), the average recovery was 101.84; The calibration curves were linear (r =0.9998) within the range of 66.1 ~ 1321.6 u g ? ml"1 for isomer P, the detection limit was 0.05 u g (S/N=3), the analysis precision RSD was less than 1.0% (?=5), the repeatability precision RSD was 0.50% (?=6), the average recovery was 100.71%. The accurate, simple and suitable method had been provided for the quality control of TBS material in this research.Recently, the generation and development of drug-resistance bacterium was gradually serious, which was one of the important reasons why the clinical therapeutic effect of antibiotics was affected. When the drug resistant mechanism was clear, one of the measures to degrade antibiotic resistance was to design a drug combination plan[5]. Cephalosporin belonged to (3 -lactam antibiotics. One of the main reasons why it had drug resistance was that p-lactamase which could hydrolyze antibiotic was formed by bacterium. Therefore, one of the effective methods to solve the drug resistance of P -lactam antibiotics was to applyassociatedly with |3 -lactamase inhibitor16"71. Sulbactam(SUL) was acompetively nonreversible p-lactamase inhibitor. When it composed compound preparation for drug combination with cephalosporin, the stability of Ceftriaxone to P-lactamase and the antibacterial activity of Ceftriaxone to the strain which could produce enzyme were enhanced, and the extent of clinical application of Ceftriaxone was enlarged too, which was verificated by pharmacodynamic test[8].Ceftriaxone Sodium/Sulbactam Sodium for Injection (CFS, Ceftriaxone : Sulbactam=4:1, g/g) was a new broad-spectrum antibiotics of complex prescription which was developed by medicine college of Sichuan university and HaiShen pharmacy corporation in Hainan. Ceftriaxone(CEF) was the third generation semisynthetic cephalosporin and had intensive inhibitory action against various pathogenic bacteria^9 . Although, the pharmacodynamic action and security that Ceftriaxone Sodium and Sulbactam Sodium was separately applied at clinic had already been confirmed. With regard to the new compound preparation (belonged to chemicals registration classification 1) which was composed of both, according to the drug registration management measure, the pharmacodynamic action, toxicity and pharmacokinetic interaction of the various composition in compound preparation should be tested. To investigate the pharmacokinetic characteristics in dogs' in vivo of Ceftriaxone Sodium/Sulbactam Sodium for injection, Ceftriaxone Sodium for injection and Sulbactam Sodium, to compare the difference in kinesics between Ceftriaxone and Sulbactam by itself and united administration, to offer foundation of feasibility of its research and clinical rational administration, the assay by HPLC of Ceftriaxone and Sulbactam in the plasma was established and the test of pharmacokinetic interaction of the two composition in CFS was performed in this article.In this study, the pretreatment method that plasma protein was precipited by methanol was chosen before RP-HPLC analysis. The concentrations of Ceftriaxone and Sulbactam in the plasma were determined separately withdifferent mobile phase and chromatographic condition. Ceftriaxone or Sulbactam and its impurity were separated on Hypersil Cjg column! 250x4.6mm, 10|nm) with methanol-30mmol/L phosphate buffer as the mobile phase by RP-HPLC. Ceftriaxone was detected at 240nm and Sulbactam was detected at 200nm. The calibration curves were linear (r>0.999) within the range of 1.27-3227.0 fxg/ml for Ceftriaxone and the range of 1.25~622.5 |J.g/ml for Sulbactam. The detection limit was 13ng (S/N=3) for Ceftriaxone and 12ng (S/N=3) for Sulbactam. The recovery of application of sample in vacuity for Ceftriaxone and Sulbactam (according to mean) were 91.9%* 94.7%. Intra-day and inter-day precision of Ceftriaxone and Sulbactam were both less than 6.2% (?=5). This method could be used for the investigation of pharmacokinetics of Ceftriaxone and Sulbactam in dogs' in vivo. The pharmacokinetic study of Ceftriaxone and Sulbactam was performed in six healthy Beagle dogs after intravenous (i.v.) injection of Ceftriaxone Sodium/Sulbactam Sodium for injection, Ceftriaxone Sodium for injection and Sulbactam Sodium with single dosage by the established analytical method. The experimental data showed that the concentration-time curve of Ceftriaxone and Sulbactam in dog plasma could be fitted to two-compartment model. The main pharmacokinetic parameters of Ceftriaxone after intravenous (i.v.) injection of Ceftriaxone Sodium for injection and Ceftriaxone Sodium/Sulbactam Sodium for injection with single dosage were as follows: the area under the plasma concentration-time curve (AUC) were 2026.2±550.1 mg-h-L"1 and 2025.5±791.8 mg-h-L"1 respectively; The elimination half life (ti/2, p) were 1.43±0.49h and 1.13±0.42h respectively. The main pharmacokinetic parameters of Sulbactam after intravenous (i.v.) injection of Sulbactam Sodium and Ceftriaxone Sodium/Sulbactam Sodium for injection with single dosage were as follows: the area under the plasma concentration-time curve (AUC) were 326.8±17.2mgh-L" and 356.8±38.8 mg-h-L"1 respectively; The elimination half life (t\a, p) were1.20±0.60h and 0.87±0.14h respectively. After intravenous (i.v.) injection of Ceftriaxone Sodium for injection and Ceftriaxone Sodium/Sulbactam Sodium for injection with single dosage, it was believed that AUCo->oc* AUCo->t^ tm, p. Cl and Vc of Ceftriaxone had no significance respectively by analysis of variance and pared-samples T test (P>0.05); After intravenous (i.v.) injection of Sulbactam Sodium and Ceftriaxone Sodium/Sulbactam Sodium for injection with single dosage, it was believed that AUC0->oc> AUCo_>t> ti,2,p. Cl and Vc of Sulbactam had no significance respectively by analysis of variance and pared-samples T test (P>0.05).It was believed in the study that the characteristics in pharmacokinetics of Ceftriaxone and Sulbactam had no modification, after they composed compound preparation of Ceftriaxone Sodium/Sulbactam Sodium for injection, and two of them had no ineraction each other in dogs. The results had offered foundation of feasibility of its research and clinical rational administration... |
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