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Sirolimus self-microemulsion-mesoporous silicon sustained release tablets were prepared in order to improve the dissolution of the insoluble drug sirolimus and reduce its side effects. Firstly, sirolimus self-microemulsion was prepared and cured with mesoporous silicon. Secondly, the suitable excipients were selected according to the appearance, hardness and in vitro release rate. The sustained-release tablets with hydroxypropyl methylcellulose (HPMC) as skeleton material were prepared by powder direct pressing method, and the formulation was optimized by central composite design-response surface method to investigate the drug release in vitro. Finally, the pharmacokinetics was carried out in beagle dogs using the commercial sirolimus tablets as references. The final formulation of sustained-release tablets is as follows: 162 mg of sirolimus self-microemulsion-mesoporous silica (1∶1, w/w), 80 mg of HPMC K4M and 80 mg of carboxymethyl starch sodium, the microcrystalline cellulose is 168 mg. The results of in vitro release test showed that the self-made sustained-release tablets released slowly within 12 h, which conformed to the Ritger-Peppas model. The in vivo test results showed that compared with the commercial sirolimus tablets, the Cmax of the sustained-release tablets decreased by 49.47%, the Tmax of the sustained-release tablets was prolonged by 5.1 times, and the relative bioavailability was 105.81%. Sirolimus self-microemulsion-mesoporous silicon sustained-release tablets have good sustained-release effects in vitro and in vivo, which provides a reference for the solubilization of other insoluble drugs and the research and development of sustained-release preparations. Animal experiments and welfare processes were reviewed and approved by the Animal Ethics Committee of the 900TH Hospital of the Joint Logistics support Force.
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Objective: To investigate the effect of sodium carboxymethyl starch (CMC) on constipation. Methods:The slow transit constipation model of mice was established by intragastric administration of loperamide for 3 d, and the dehydration-dryness constipation model of mice was established by water deprivation for 3 d. The effects of CMC were evaluated by total fecal grains, intestinal propulsion rate, fecal water content and intestinal fluid within 3 h after administration. Results: The total defecation granules in the slow transit constipation model group were (7.9±6.0) within 3 h after administration for 3 d. Compared with those in the model group, the total defecation granules in the three CMC dosage groups (0.45, 0.9 and 1.8 g/kg) significantly increased (18.5±5.0, 17.3±8.3 and 22.9±8.4, P<0.01), respectively. The results were better than those in mosapride group (14.3±8.4). The intestinal propulsion rate [(75.3±9.2)%, (78.7±9.6)%, and (79.4±8.0)%] in the three CMC dosage groups increased significantly (P<0.05 or P<0.01) compared with the model group (63.0±13.6)%. For dehydration and dryness constipation model, the total fecal granules in 0.9 and 1.8 g/kg CMC groups were 37.9±9.9 and 37.2±7.9, which significantly increased compared with those in model group (25.8±8.5, P<0.01). The intestinal propulsive rate (83.2±12.8)% was higher in CMC 1.8 g/kg group than in the model group [(72.6±11.5)%, P<0.05]. Mouse fecal water content [(56.0±4.1)%, (57.7±10.4)% and (60.2±6.8%)] in CMC 0.3, 0.6 and 1.2 g/kg groups were higher than in the model group [(49.0±6.8)%, P<0.05 or P<0.01]. Rat intestinal solution in CMC 0.6 and 1.2 g/kg groups was higher than that in saline group (P<0.05 or P<0.01). Conclusion: CMC can improve the defecation of constipated mice.
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Objective: To investigate the physicochemical properties of sodium carboxymethyl starch(CMS) and its effect on erythrocyte rheology and oxygen carrying function. Methods According to the requirements of Chinese Pharmacopoeia,the physicochemical properties were determined for CMS120,CMS380 and hydroxyethyl starch 130 (HES130),including pH value,osmotic pressure molar concentration and viscosity. Normal saline,CMS120,CMS380 and HES130 were mixed with whole blood(7:3,V/V),respectively,and the experimental groups were set as whole blood group,whole blood+normal saline(NSB)group,whole blood+CMS120(CMS120B)group,whole blood+CMS380 (CMS380B)group,and whole blood+HES130(HES130B)group. The colloid osmotic pressure,blood viscosity,eryth- rocyte deformation and aggregation,and the partial pressure of oxygen when blood oxygen saturation was 50%(P50)val- ue were measured for each of these groups. Results: The osmotic pressure molar concentration and the viscosity of CMS120 and CMS380 were both significantly higher than those of HES130(all P<0.05)as indicated by the determina- tion of physicochemical properties. Compared with the whole blood group,the colloid osmotic pressure was significantly increased in the CMS380B and CMS120B groups(P<0.05),which was also significantly higher than that in the HES130B group(P<0.05). At low shear rate(10/s),compared with the whole blood group,the whole blood and the plasma vis- cosities were significantly increased in the NSB,CMS380B and CMS120B groups(all P<0.05),but the whole blood viscosity was significantly decreased in the HES130B group(P<0.05). Under the conditions of shear rate 10/s,50/s and 150/s,compared with the HBS130B group,the whole blood and the plasma viscosities were both significantly in- creased in the CMS120B and CMS380 groups(all P<0.05). At the effect of high shear rate,both the CMS380 and HES130 groups showed a tendency to promote erythrocyte deformation,and the CMS120B and CMS380B groups promot- ed erythrocyte aggregation,while the HES130B group inhibited erythrocyte aggregation amplitude(P<0.05). The P50 value was significantly higher in the CMS380B group than in the HES130B group(P<0.05). Conclusion: CMS130 and CMS380 could improve the rheological properties of erythrocytes and CMS380 could also promote the oxygen release of erythrocytes.
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The study sought to evaluate the functional properties of sodium carboxymethyl starch obtained from Ipomoea batatas, in order to facilitate their exploitation as substitute excipients for the local pharmaceutical manufacturing industry. The sodium carboxymethyl starch was produced by reacting native starch with sodium hydroxide and sodium monochloroacetate in various proportions and reaction time at constant temperature. Subsequently, the starches were obtained by wet separation techniques. Physicochemical properties and proximate analysis were carried out in order to determine their suitability for pharmaceutical use. Differences in the physicochemical properties, proximate composition, and functional properties of sodium carboxymethyl starches and native Ipomoea batatas starch were significant. Optimum degree of substitution and reaction efficiency of 0.52 and 1.92% were achieved when sodium hydroxide and sodium monochloroacetate in a ratio 1.5 and 2.0 Mole per anhydrous glucose unite respectively in 6 hrs was used. Generally, the carboxymethyl starches had higher bulk density, tapped density, true density, hydration and swelling capacity as compared to the native starch.