目的制备用于治疗溃疡性结肠炎的pH依赖型愈肠宁结肠靶向片(pH-dependen t Y uchangn ing T ab let forco lon-spec ific de livery,PYTCSD),并对其体内外释放性能进行评价,探讨制备中药结肠靶向制剂的可行性。方法以苦参碱和氧化苦参...目的制备用于治疗溃疡性结肠炎的pH依赖型愈肠宁结肠靶向片(pH-dependen t Y uchangn ing T ab let forco lon-spec ific de livery,PYTCSD),并对其体内外释放性能进行评价,探讨制备中药结肠靶向制剂的可行性。方法以苦参碱和氧化苦参碱体外释放度为指标,对制剂的包衣处方进行筛选;采用体外释放度测定法考察该制剂的体外释放性能;采用硫酸钡造影技术对该制剂在人体内的释放性能进行评价。结果拟订了PYTCSD的制备方法:将药物制备得片芯后,以质量浓度3.70%(g/mL)丙烯酸树脂Ⅲ(Eudrag itⅢ)、0.37%(g/mL)邻苯二甲酸二乙酯(DEP)、0.93%(g/mL)滑石粉的乙醇混悬溶液为包衣液,包衣使片芯增重8%,即得;体外释放度测定结果表明,在人工胃液2 h时溶出液中未检测到苦参碱和氧化苦参碱,在人工小肠液4 h时两指标累积溶出率均<10%,而在人工结肠液1 h时苦参碱和氧化苦参碱分别累积溶出86.5%和86.8%;体内释放度试验结果表明,PYTCSD在8名志愿者体内均能完整到达回盲部或升结肠,并在上述部位崩解释放出药物。结论制备得pH依赖型愈肠宁结肠靶向片能达到较好结肠定位释药的目的。展开更多
AIM:To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro.METHODS:Acute colitis was induced with trinitrobenzene sulfonic acid(TNBS)in male Wistar ...AIM:To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro.METHODS:Acute colitis was induced with trinitrobenzene sulfonic acid(TNBS)in male Wistar rats.Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration.The distal colon was removed to evaluate the various parameters of inflammation.Moreover,wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial(RIE)cells treated with rebamipide.RESULTS:Intracolonic administration of rebamipide accelerated TNBSinduced ulcer healing.Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide.The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signalregulated kinase(ERK)and activation of Rho kinase.CONCLUSION:Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells,via ERK activation.Rebamipide might be a novel therapeutic approach for inflammatory bowel disease.展开更多
Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract that is defi ned by relapsing and remitting episodes. Tumor necrosis factor alpha (TNF-α) appears to play a central role in the pat...Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract that is defi ned by relapsing and remitting episodes. Tumor necrosis factor alpha (TNF-α) appears to play a central role in the pathophysiology of the disease. Standard therapies for inflammatory bowel disease fail to induce remission in about 30% of patients. Biological therapies have been associated with an increased incidence of infections, especially infection by Mycobacterium tuberculosis (Mtb). Thalidomide is an oral immunomodulatory agent with anti-TNF-α properties. Recent studies have suggested that thalidomide is effective in refractory luminal and fistulizing Crohn's disease. Thalidomide costimulates T lymphocytes, with greater effect on CD8+ than on CD4+ T cells, which contributes to the protective immune response to Mtb infection. We present a case of Crohn's disease with gastric, ileal, colon and rectum involvement as well as steroid dependency, which progressed with loss of response to infliximabafter three years of therapy. The thorax computed tomography scan demonstrated a pulmonary nodule suspected to be Mtb infection. The patient was started on thalidomide therapy and exhibited an excellent response.展开更多
Crohn's disease and ulcerative colitis are progressive diseases associated with a high risk of complications over time including strictures,fistulae,perianal complications,surgery,and colorectal cancer.Changing th...Crohn's disease and ulcerative colitis are progressive diseases associated with a high risk of complications over time including strictures,fistulae,perianal complications,surgery,and colorectal cancer.Changing the natural history and avoiding evolution to a disabling disease should be the main goal of treatment.In recent studies,mucosal healing has been associated with longer-term remission and fewer complications.Conventional therapies with immunosuppressive drugs are able to induce mucosal healing in a minority of cases but their impact on disease progression appears modest.Higher rates of mucosal healing can be achieved with anti-tumor necrosis factor therapies that reduce the risk of relapse,surgery and hospitalization,and are associated with perianal fistulae closure.These drugs might be able to change the natural history of the disease mainly when introduced early in the course of the disease.Treatment strategy in inflammatory bowel diseases should thus be tailored according to the risk that each patient could develop disabling disease.展开更多
Infliximab (IFX) is currently the only biologic therapy used in the treatment of moderate-to-severe ulcerative colitis (UC). In the years to come, more biologic therapies will have a role in the management of moderate...Infliximab (IFX) is currently the only biologic therapy used in the treatment of moderate-to-severe ulcerative colitis (UC). In the years to come, more biologic therapies will have a role in the management of moderate-to-severe UC. We report on two patients with steroid-dependent UC who, due to adverse reactions to IFX, have been under therapy with adalimumab for two years. Both patients received concomitant immunosuppressive treatment. Long term clinical remission and mucosal healing are described.展开更多
Objective： To observe the clinical therapeutic effect of dampness, promoting blood circulation and healing ulcer on the method of clearing away heat, expelling ulcerative colitis. Methods： The 100 cases were randoml...Objective： To observe the clinical therapeutic effect of dampness, promoting blood circulation and healing ulcer on the method of clearing away heat, expelling ulcerative colitis. Methods： The 100 cases were randomly divided into a control group of 45 cases treated with retention enema of the enterosoluble tablet sulfasalazine once every evening and a treatment group of 55 cases treated with retention enema of the decoction for clearing away heat, expelling dampness, promoting blood circulation and healing ulcer once every evening. The patients in both groups orally took Chinese drug for basic treatment for 30 days as a course. After treatment, the clinical therapeutic effects in the 2 groups were compared and changed symptoms in intestinal mucosa were observed under endoscope. Results： The total effective rate of treatment group was better in relieving symptoms of TCM syndrome （90.9%） and intestinal mucosa （83.3%） than that of control group （68.9%, 56.3%） （P〈0.01 or P〈0.05）. Conclusion： With good therapeutic effect on ulcerative colitis, Qinghua Huoxue Lianyang therapy （clearing away heat, expelling dampness, promoting blood circulation and healing ulcer） can obviously repair intestinal mucosa.展开更多
文摘目的制备用于治疗溃疡性结肠炎的pH依赖型愈肠宁结肠靶向片(pH-dependen t Y uchangn ing T ab let forco lon-spec ific de livery,PYTCSD),并对其体内外释放性能进行评价,探讨制备中药结肠靶向制剂的可行性。方法以苦参碱和氧化苦参碱体外释放度为指标,对制剂的包衣处方进行筛选;采用体外释放度测定法考察该制剂的体外释放性能;采用硫酸钡造影技术对该制剂在人体内的释放性能进行评价。结果拟订了PYTCSD的制备方法:将药物制备得片芯后,以质量浓度3.70%(g/mL)丙烯酸树脂Ⅲ(Eudrag itⅢ)、0.37%(g/mL)邻苯二甲酸二乙酯(DEP)、0.93%(g/mL)滑石粉的乙醇混悬溶液为包衣液,包衣使片芯增重8%,即得;体外释放度测定结果表明,在人工胃液2 h时溶出液中未检测到苦参碱和氧化苦参碱,在人工小肠液4 h时两指标累积溶出率均<10%,而在人工结肠液1 h时苦参碱和氧化苦参碱分别累积溶出86.5%和86.8%;体内释放度试验结果表明,PYTCSD在8名志愿者体内均能完整到达回盲部或升结肠,并在上述部位崩解释放出药物。结论制备得pH依赖型愈肠宁结肠靶向片能达到较好结肠定位释药的目的。
基金Supported by A GrantinAid for Scientific Research(B)to Toshikazu Yoshikawa(Grant No.21390184)Challenging Exploratory Research to Yuji Naito(No.08101559)from the Japan Society for the Promotion of Science+1 种基金A City Area Program to Toshikazu Yoshikawa and Yuji Naito from Ministry of Education,Culture,Sports,Science and Technology,JapanAn Adaptable and Seamless Technology Transfer Program through targetdriven R&D to Yuji Naito from Japan Science and Technology Agency
文摘AIM:To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro.METHODS:Acute colitis was induced with trinitrobenzene sulfonic acid(TNBS)in male Wistar rats.Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration.The distal colon was removed to evaluate the various parameters of inflammation.Moreover,wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial(RIE)cells treated with rebamipide.RESULTS:Intracolonic administration of rebamipide accelerated TNBSinduced ulcer healing.Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide.The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signalregulated kinase(ERK)and activation of Rho kinase.CONCLUSION:Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells,via ERK activation.Rebamipide might be a novel therapeutic approach for inflammatory bowel disease.
文摘Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract that is defi ned by relapsing and remitting episodes. Tumor necrosis factor alpha (TNF-α) appears to play a central role in the pathophysiology of the disease. Standard therapies for inflammatory bowel disease fail to induce remission in about 30% of patients. Biological therapies have been associated with an increased incidence of infections, especially infection by Mycobacterium tuberculosis (Mtb). Thalidomide is an oral immunomodulatory agent with anti-TNF-α properties. Recent studies have suggested that thalidomide is effective in refractory luminal and fistulizing Crohn's disease. Thalidomide costimulates T lymphocytes, with greater effect on CD8+ than on CD4+ T cells, which contributes to the protective immune response to Mtb infection. We present a case of Crohn's disease with gastric, ileal, colon and rectum involvement as well as steroid dependency, which progressed with loss of response to infliximabafter three years of therapy. The thorax computed tomography scan demonstrated a pulmonary nodule suspected to be Mtb infection. The patient was started on thalidomide therapy and exhibited an excellent response.
文摘Crohn's disease and ulcerative colitis are progressive diseases associated with a high risk of complications over time including strictures,fistulae,perianal complications,surgery,and colorectal cancer.Changing the natural history and avoiding evolution to a disabling disease should be the main goal of treatment.In recent studies,mucosal healing has been associated with longer-term remission and fewer complications.Conventional therapies with immunosuppressive drugs are able to induce mucosal healing in a minority of cases but their impact on disease progression appears modest.Higher rates of mucosal healing can be achieved with anti-tumor necrosis factor therapies that reduce the risk of relapse,surgery and hospitalization,and are associated with perianal fistulae closure.These drugs might be able to change the natural history of the disease mainly when introduced early in the course of the disease.Treatment strategy in inflammatory bowel diseases should thus be tailored according to the risk that each patient could develop disabling disease.
文摘Infliximab (IFX) is currently the only biologic therapy used in the treatment of moderate-to-severe ulcerative colitis (UC). In the years to come, more biologic therapies will have a role in the management of moderate-to-severe UC. We report on two patients with steroid-dependent UC who, due to adverse reactions to IFX, have been under therapy with adalimumab for two years. Both patients received concomitant immunosuppressive treatment. Long term clinical remission and mucosal healing are described.
基金supported by a grant from TCM Scientific Research Project of Jiangsu Province (No.18)
文摘Objective： To observe the clinical therapeutic effect of dampness, promoting blood circulation and healing ulcer on the method of clearing away heat, expelling ulcerative colitis. Methods： The 100 cases were randomly divided into a control group of 45 cases treated with retention enema of the enterosoluble tablet sulfasalazine once every evening and a treatment group of 55 cases treated with retention enema of the decoction for clearing away heat, expelling dampness, promoting blood circulation and healing ulcer once every evening. The patients in both groups orally took Chinese drug for basic treatment for 30 days as a course. After treatment, the clinical therapeutic effects in the 2 groups were compared and changed symptoms in intestinal mucosa were observed under endoscope. Results： The total effective rate of treatment group was better in relieving symptoms of TCM syndrome （90.9%） and intestinal mucosa （83.3%） than that of control group （68.9%, 56.3%） （P〈0.01 or P〈0.05）. Conclusion： With good therapeutic effect on ulcerative colitis, Qinghua Huoxue Lianyang therapy （clearing away heat, expelling dampness, promoting blood circulation and healing ulcer） can obviously repair intestinal mucosa.
