Effect of Xileisan temperature-sensitive gels on endothelial nitric oxide synthase, vascular endothelial growth factor A and tumor necrosis factor-α expression in rats with bleeding internal hemorrhoids / 预防医学

Objective@#To investigate the effect of Xileisan temperature-sensitive gels on endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor A (VEGF-A) and tumor necrosis factor-α (TNF-α) expression in rats with bleeding internal hemorrhoids, so as to provide insights into the illustration of the pathogenesis of internal hemorrhoid hemorrhage. @*Methods@#Thirty six-week-old SPF-graded rats of the SD strain were randomly divided into the normal group, model group and Xileisan temperature-sensitive gel group, of 10 rats in each group (half male and half female). Cotton balls were soaked with 0.16 mL of croton oil mixture and then inserted into the anus of rats in the model group and Xileisan temperature-sensitive gel group for 10 s. After 6 h when the rectal mucosa tissues presented remarkable swelling, the perianal mucosa was rubbed repeatedly with a rough glass rod until the glass rod was bloody. Following successful modeling, rats in the Xileisan temperature-sensitive gel group was given rectal administration of Xileisan temperature-sensitive gel at a dose of 0.5 mL/d, while animals in the normal group and model group were given rectal administration of the blank gel at the same dose. Following administration for 7 successive days, rats were sacrificed, and the hemorrhoids tissues were collected for pathological examinations. The eNOS, VEGF-A and TNF-α expression was determined using immunohistochemistry and compared among groups.@*Results@#Compared with the normal group, the rat hemorrhoids mucosa showed inflammatory changes in the model group, with submucosal congestion and edema, blood vessel congestion and dilation, and visible new blood vessels, and remarkable improvements were seen in the hemorrhoid mucosal inflammation in the Xileisan temperature-sensitive gel group. There were significant differences in the integrated option density (IOD) of eNOS and VEGF-A expression in rat hemorrhoids tissues among the three groups (P<0.05), and no gender-specific differences were seen (P>0.05). The IOD values of eNOS (45.84±13.66) and VEGF-A expression (45.89±9.06) were higher in rat hemorrhoids tissues in the model group than in the normal group (23.11±5.64 and 27.91±11.65) and the Xileisan temperature-sensitive gel group (27.41±8.89 and 33.44±6.20) (P<0.05), while no significant differences were detected in the IOD of TNF-α expression in rat hemorrhoids tissues among the three groups (P>0.05).@*Conclusion@#Xileisan temperature-sensitive gel may alleviate inflammation and internal hemorrhoids hemorrhage through inhibiting eNOS and VEGF-A expression in rat hemorrhoids tissues.

Intranasal tetrandrine temperature-sensitive gel for treatment of post-traumatic stress disorder / 药学学报

The traditional systemic treatment of post-traumatic stress disorder (PTSD) requires a long time period for an effect and has obvious side effects. In this study, tetrandrine temperature-sensitive gel (TTG) was prepared for treatment of PTSD in mice by nasal administration. TTG was prepared with poloxamer as matrix, the gelation temperature was suitable (<32 ℃) and the gelation time was short (1.32 min). Rheology experiments demonstrated that TTG has temperature sensitivity. In vivo imaging system of small animals proved that TTG nasal cavity retention time was so long. The cilia toxic test of toad showed that the formulation was safe. Animal experiments were approved by the Ethics Committee of Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences and the experiments were conducted in accordance with relevant guidelines and regulations. The mice were randomly assigned into healthy group, model group and TTG group. The PTSD model of mice was established by single prolonged stress (SPS) and foot-shock method to generate anxiety and fear behavior. On the day 0 of TTG administration, SPS model mice were evaluated by the elevated plus maze (EPM). Percentages of open arm entries number (OE), latency of open arm entries (OL) and the residence time of open arm entries (OT) all indicated that the SPS model was successfully established. On the 7th day of TTG administration, TTG increased the OE and OT, decreased the OL of SPS mice. The feard behavior of mice in the foot-shock model was tested using conditioned fear box, 7 days of TTG treatment can reduce the freezing time of the mice obviously. The pathological changes of hippocampus, prefrontal cortex and amygdala were observed by H&E histological sections and c-fos immunohistochemical expression. The main influenced areas of PTSD were revealed to be the CA1 of hippocampus, prefrontal cortex and amygdala. All of the above indicated that TTG is a convenient, safe and effective drug for PTSD treatment, and will provide a new choice for clinical management of PTSD.

Preparation and preliminary evaluation of chitosan composite KGF-2 mutant thermal sensitive dressing / 军事医学

Objective To develop chitosan composite keratinocyte growth factor-2 mutant(KGF-2M)temperature-sen-sitive dressing and evaluate its physicochemical properties and dynamic release rule were used.Methods Chitosan, chi-tosan quaternary ammonium salt,β-glycerophosphate and other adjuvant materials to configure different formulations which were compounded with KGF-2M in order to develop temperature-sensitive dressing.Gelling time, temperature,the release rate of KGF-2M and other indicators were measured to analyze the physical and chemical properties of the temperature -sen-sitive dressing.Results Chitosan-KGF-2M composite dressing with temperature-sensitive properties was obtained by opti-mizing the formulation components of chitosan and related adjuvant materials.When the liquid dressing was above 35℃,it could be converted from liquid to solid gelatin within 10 minutes.The compound KGF-2M released from the gel was more than 98%at 4 h,and its bioactivity remained stable.Conclusion The thermo-sensitive gel has the characteristics of good conformability,moisturizing(moisture),isolation,wound healing,and a controlled release effect,which has great potential in wartime for wound repair.

Preparation and Quality Analysis of Osthole Microcapsules-Temperature-sensitive Gel / 中国药学杂志

OBJECTIVE: To optimize the preparation process of osthole microcapsules-temperature-sensitive gel and set up its quality standard. METHODS: Using gelling temperature as the indicator, P407, P188 and the concentration of propylene glycol were investigated by single factor test, and orthogonal experiment was conducted to optimize the preparation process of osthole microcapsules-temperature-sensitive gel. Osthole content was determined by HPLC. The quality standard of osthole microcapsules-temperature-sensitive gel was established. RESULTS: The optimal formulation of osthole microcapsules-temperature-sensitive gel was as followsP407-P188-propylene glycol=18%∶1%∶15%. Osthole contentin the osthole microcapsules-temperature-sensitive gel should not be less than 31.77 μg·mL-1, and the gelling temperature should be 36-37℃. CONCLUSION: Osthole microcapsules-temperature-sensitive gel prepared in this study has reasonable composition, simple preparation process, and stable quality standards, indicating a hopeful application prospect.

Formula Screening and in vitro Drug Release of Tegafur Thermo-sensitive Gel for Intratumor Injection / 中国药师

Objective:To screen the best formula of tegafur temperature-sensitive gel for intratumor injection and investigate the in vitro drug release behavior. Methods:The drug dose was determined by cytotoxicity experiment. The thermo-sensitive gel was prepared with PLGA-PEG-PLGA and HPMC as the matrix. With the in vitro release as the index, the effects of PLGA-PEG-PLGA and HPMC at different concentrations on gel were investigated. The gelation temperature, viscosity and pH were detected. Results:The best formula was as follows:25% PLGA-PEG-PLGA, 1% HPMC, and tegafur dose of 1 mg·ml-1 . The average gelation temperature was 36. 7℃, the average viscosity was 7550 mPa·s, and the average pH was 7. 2. Conclusion:Tegafur thermo-sensitive gel for intratumor in-jection shows temperature sensitivity and obvious sustained-release property, which provides experimental basis for the further clinical research.