| Ultrasonic microvesicle locating and targeting drug is a new kind of targeting drug system.It start a new study field. We can observe the running condition with microvesicle in vivo through ultrasonic imaging. Microvesicle can be destroyed and release drug under the ultrasonic physical effect. The purposes are targeting drug,lower medicine dosage,and slight adverse reaction. Therefore ultrasonic microvesicle locating and targeting drug have wide application prospect and enormous economic retums..HCPT is the only one specific inhibitor in topoismerase in clinic. HCPT can treat some malignant tumors,such as primary hepatic carcinoma,stomach cancer,leukemia and so on.Also it has high performance,low side effect,achiasmate tolerance and security.It is a novel kind of chemotherapeutics.But it have bone marrow depression and tox in alimentary canal.Therefore,the new dosage form of HCPT is a problem in urgently.The study prepare the HCPT ultrasonic microvesicle with the PLGA film-former. Part one: Preparation the praeparatum of ultrasonic microvesicles loaded HCPT1. Set up assaying by UV: The standard curve was A=0.0737C-0.1573(r=0.9994).There was a good linear relationship within the concentration range of 5.88μg·mL-1-11.76μg·mL-1 of HCPT. The degree of precision,recovery rate and stability were all fit the technology request.2.Using the modified compound emulsion-dispersion solvent evaporation method and cryodesiccation technology which were used in microvesicles preparation.3. Single factor experiments were used to screening the preparation method:the volume ratio between inneraqueous phase and oil phase was 1:10, the ultrasound power in emulsion was 200w, time was 90s, the ultrasound power in multiple emulsion was 100w, time was 60s, the speed of stirring was 600rpm.It can prepare the blank microvesicle of mean diameter was 433nm.4. Make the envelopment to be the consideration index.The experiment got the optimize form.HCPT was 25.0mg, PLGA was 1.8750g, the volume ratio between emulsion and ouside aqueous phase was 1:15, PVA concentration was 3%. The envelopment was 79.92%,dosage of them was 0.4783%.5. The initial stability investigat microvesicles had a good stability in 56d with freeze drying powder at 4℃. Part two: evaluation of praeparatum of ultrasonic microvesicles loaded HCPT in pharmacy1.Set up the method of release in vitro : The standard curve was A=491.77C+1601.8(r=0.9994).There was a good linear relationship within the concentration range of 0.41μg·mL-1-8.20μg·mL-1 of HCPT. The degree of precision,recovery rate and stability were all fit the technology request.2.The shape of microvesicles was round and smooth.The mean diameter was 715nm.The particle diameter range was 0.50-0.90μm. Electric charge were between -40-0mv .The appearance and dispersivity were good. Microvesicles can be destroyed under ultrasound.3. Microvesicles increased the ultrasound signal.And image was good in vitro.4.Study microvesicles'dilivery in vitro under two circumstance.It shows the delivery of microvesicles consistent the feature of extended release dosage system.About 10d,the drug was released elementary.And the drug was released in 30min under the ultrasound.Part three: image praeparatum of ultrasonic microvesicles loaded HCPT in vivoMicrovesicle could remarkably enhance ultrasonic image in liver and tumor in liver. It provided a straight and dependable foundation in ultrasonic targeting drug system. Through the study of praeparatum of ultrasonic microvesicles loaded HCPT,the topic have four features:①There are many kinds of new deliver system,such as microballoons and liposomes.But there were problems with low targeting and low carbinoxamine compound drops. The praeparatum of ultrasonic microvesicles loaded HCPT solve this kind problems.The druges can be protected in the microvesicles. In this way,druges can play the best therapeutic efficacy.By ultrasound targeting drugs,it can increase the drug concentration in targeting area obviously and cut down the adverse effect.The correlated reports about ultrasonic microvesicles loaded HCPT was never heard.②By the technology and optimize form,we can get ultrasonic microvesicles with higher envelopment.Also the shape was round,dispersivity was good,particle diameter and electric charge distribute were uniformity.The image were good.③Set up assaying by UV and HPLC. Investigate the dosage,envelopment and delivery.To establish a base for ultrasonic microvesicle.④Observe the ltrasonic microvesicle ultrasonic imaging in liver anf livertumor.It was worth to develop the ultrasonic targeting drug system. |
PDF Full Text Request