复方去甲斑蝥素胃内滞留漂浮型缓释片的研究
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摘要
复方去甲班蝥素胃内滞留漂浮型缓释片由去甲班蝥素、黄芪、白及组成,通过延长药物在胃癌病人病变部位的作用时间提高药效。
将三种粒径黄芪均采用四种方法:水醇双提法、纤维素酶法、氧化钙溶液法、超声波法优选提取,并结合超滤技术、大孔吸附树脂技术对提取物进行纯化。得率是生药的3.55%,体积比醇、水提取分别减少9%和24%。
对三种粒径自及进行大鼠无水乙醇和乙酸致胃粘膜损伤型胃溃疡抑制实验。白及粉可明显降低大鼠的溃疡面积,且白及超微粉在等效情况下,可节省1/3剂量。
应用亲水凝胶缓释骨架技术、并采用正交设计法对复方去甲班蝥素胃内滞留漂浮型缓释片的处方进行了优化,且进一步对影响片剂释放的因素进行了考察。通过比较制片工艺过程、产品外观、漂浮性能、释放特性等六项指标优选处方,优选出一种能体外3分钟以内起漂,持漂8小时以上,7-10小时释放75%的处方。并制定漂浮片标准。
应用同位素示踪技术研究了复方去甲班蝥素胃内滞留漂浮型缓释片在人体内滞留过程,体内空腹漂浮2-3小时,饱腹4-5小时。
以去甲斑蝥素为指标,探讨了其在犬体内的药物动力学行为及生物利用度。结果表明,所研制的复方去甲班蝥素胃内滞留漂浮型缓释片增加了局部浓度,吸收好,生物利用度相对于普通片为221.8%,半衰期延长2.7小时,体内滞留时间延长了5小时。故可减少用药剂量,减少毒副作用,减少给药次数。
研究表明,该制剂可于胃内漂浮,达到缓释的目的,使胃内滞留时间明显延长,并显著的增加了去甲斑蝥素的生物利用度。
The compound norcantharidin floating sustain releasing tablet(CNRT) which consisted of norcantharindin,Milkvetch Root and Common Bletilla Tuber prolongs the time of treatment in the lesion location of gastric cancer patients and improves effect.
Milkvetch Root of three granule diameters were extracted by water-alcohol co-distilling technology,cellulase degradation,calcarea solution,ultrasonic waves methods respectively.The extracts were purified by ultrafiltration and Macro Absorption Resin.The yield coefficient is about 3.55%,volume of extractive is reduced 9%and 24%respectively than the alcohol and water extractive.
Common Bletilla Tuber of three granule diameters were used to test the albino rat gastric ulcer by anhydrous alcohol and acetic acid inhibiting effect.The Common Bletilla Tuber power can decrease significantly the GU area,and the dosage of Common Bletilla Tuber ultramicro powder,at the same effect,was 1/3 of normal.
We adopted hydrophilic sustained-release matrix and orthogonal design method to optimize the formulation of the compound norcantharidin floating sustain releasing tablet.We reviewed other factors which affected drug release of this medicine.By comparing the six aspects of process,appearance of the tablets,floating ability and release characteristics,an optimized formulation was chosen to float within 3 minutes in vitro and continuing over 8 hours on simulated gastric fluid,and 7-10 hours releasing 75%.Drawing up the standard of floating tablet.
According to the isotope tracer technique,the process of tablet remained in stomach was observed.In vivo,floating 2-3 hours on limosis,4-5 hours on a full stomach.
We selected norcantharidin as index to probe into pharmacokinetics and bioavailability in dog.The result shows the compound norcantharidin floating sustain releasing tablet can increase the local drug concentration,bioavailability is 221.8%of normal tablet.The half-life prolongs 2.7 hours,detention time in vivo prolong 5 hours, can reduce the dosage,reduces toxic,side effect and reduce the times of administration.
This tablet is capable of remaining buoyant on gastric fluid,it can achieve aim to sustained-release,detention time in vivo is obviously prolonged,the bioavailability of norcantharidin is enhaced evidently.
将三种粒径黄芪均采用四种方法:水醇双提法、纤维素酶法、氧化钙溶液法、超声波法优选提取,并结合超滤技术、大孔吸附树脂技术对提取物进行纯化。得率是生药的3.55%,体积比醇、水提取分别减少9%和24%。
对三种粒径自及进行大鼠无水乙醇和乙酸致胃粘膜损伤型胃溃疡抑制实验。白及粉可明显降低大鼠的溃疡面积,且白及超微粉在等效情况下,可节省1/3剂量。
应用亲水凝胶缓释骨架技术、并采用正交设计法对复方去甲班蝥素胃内滞留漂浮型缓释片的处方进行了优化,且进一步对影响片剂释放的因素进行了考察。通过比较制片工艺过程、产品外观、漂浮性能、释放特性等六项指标优选处方,优选出一种能体外3分钟以内起漂,持漂8小时以上,7-10小时释放75%的处方。并制定漂浮片标准。
应用同位素示踪技术研究了复方去甲班蝥素胃内滞留漂浮型缓释片在人体内滞留过程,体内空腹漂浮2-3小时,饱腹4-5小时。
以去甲斑蝥素为指标,探讨了其在犬体内的药物动力学行为及生物利用度。结果表明,所研制的复方去甲班蝥素胃内滞留漂浮型缓释片增加了局部浓度,吸收好,生物利用度相对于普通片为221.8%,半衰期延长2.7小时,体内滞留时间延长了5小时。故可减少用药剂量,减少毒副作用,减少给药次数。
研究表明,该制剂可于胃内漂浮,达到缓释的目的,使胃内滞留时间明显延长,并显著的增加了去甲斑蝥素的生物利用度。
The compound norcantharidin floating sustain releasing tablet(CNRT) which consisted of norcantharindin,Milkvetch Root and Common Bletilla Tuber prolongs the time of treatment in the lesion location of gastric cancer patients and improves effect.
Milkvetch Root of three granule diameters were extracted by water-alcohol co-distilling technology,cellulase degradation,calcarea solution,ultrasonic waves methods respectively.The extracts were purified by ultrafiltration and Macro Absorption Resin.The yield coefficient is about 3.55%,volume of extractive is reduced 9%and 24%respectively than the alcohol and water extractive.
Common Bletilla Tuber of three granule diameters were used to test the albino rat gastric ulcer by anhydrous alcohol and acetic acid inhibiting effect.The Common Bletilla Tuber power can decrease significantly the GU area,and the dosage of Common Bletilla Tuber ultramicro powder,at the same effect,was 1/3 of normal.
We adopted hydrophilic sustained-release matrix and orthogonal design method to optimize the formulation of the compound norcantharidin floating sustain releasing tablet.We reviewed other factors which affected drug release of this medicine.By comparing the six aspects of process,appearance of the tablets,floating ability and release characteristics,an optimized formulation was chosen to float within 3 minutes in vitro and continuing over 8 hours on simulated gastric fluid,and 7-10 hours releasing 75%.Drawing up the standard of floating tablet.
According to the isotope tracer technique,the process of tablet remained in stomach was observed.In vivo,floating 2-3 hours on limosis,4-5 hours on a full stomach.
We selected norcantharidin as index to probe into pharmacokinetics and bioavailability in dog.The result shows the compound norcantharidin floating sustain releasing tablet can increase the local drug concentration,bioavailability is 221.8%of normal tablet.The half-life prolongs 2.7 hours,detention time in vivo prolong 5 hours, can reduce the dosage,reduces toxic,side effect and reduce the times of administration.
This tablet is capable of remaining buoyant on gastric fluid,it can achieve aim to sustained-release,detention time in vivo is obviously prolonged,the bioavailability of norcantharidin is enhaced evidently.
引文
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[9]吴立明.正交试验法考察黄芪的提取工艺[J].中国中医药信息杂志,2003,10(11):126
[10]江蔚新,于翔宇,石慎华,等.黄芪茎中有效成分提取方法的研究[J].哈尔滨商业大学学报,2004,20(3):273
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