伊维菌素聚乳酸纳米粒的初步研究
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摘要
本研究以聚乳酸纳米粒为载体,制备新型、高效、安全的伊维菌素纳米粒,并对其质量及其稳定性、毒性和药效进行了研究。
试验一:伊维菌素聚乳酸纳米粒的制备。采用改良的自乳化溶剂扩散法制备伊维菌素聚乳酸纳米粒,以伊维菌素作为伊维菌素纳米粒含量测定的指标性成分,建立伊维菌素纳米粒的紫外分析方法,对其回收率、精密度等进行研究。结果表明,伊维菌素纳米粒在245nm处有最大吸收,在10~80μg/mL范围内线性关系良好,其平均回收率为97.87%。回收率的相对标准偏差(RSD)为3.05%、进样重复性的RSD为1.98%、日内精密度的RSD小于5%,日间精密度的RSD小于7%。本研究建立的分析方法回收率高、精密度和重复性良好,可满足其质量控制研究。
试验二:伊维菌素聚乳酸纳米粒的质量及稳定性评价。对利用透射电镜、激光粒度分布仪、黏度计、折光仪和电导仪等对其质量进行检测;通过离心、加速、光照、低温、长期和经典恒温加速试验对其稳定性进行评价。结果表明,制备的伊维菌素聚乳酸纳米粒为淡蓝色透亮均一的液体,其平均粒径为(67.9±2.7)nm;测出其有效期为25个月。本研究制备的伊维菌素聚乳酸纳米粒质量稳定。
试验三:伊维菌素聚乳酸纳米粒的毒性研究。通过急性毒性和细胞毒性试验对伊维菌素聚乳酸纳米粒的安全性进行评价。结果表明,伊维菌素聚乳酸纳米粒对小鼠的LD50为62.675mg/kg,是原料药组的2.67倍,属于无毒级;对细胞毒性为1级,无明显毒性。本研究制备的伊维菌素聚乳酸纳米粒安全无毒。试验四:伊维菌素聚乳酸纳米粒的药效对比试验。以低剂量和高剂量的伊维菌素聚乳酸纳米粒对自然感染螨虫的兔进行治疗试验,对其药效进行初步研究。结果表明,5%、10%的伊维菌素聚乳酸纳米粒对兔螨均有较好的疗效。表明伊维菌素纳米粒是一种有开发前景的抗寄生虫新制剂。本研究制备的伊维菌素聚乳酸纳米粒药效显著。
综上所述,伊维菌素聚乳酸纳米粒制备简单,稳定性高,安全性良好,药效显著,符合纳米粒的各种特性和用药要求。
In this research, by using the poly lactic acid (PLA) as carrier, Ivermectin poly lactic acid nanoparticles (IVM-PLA-NPs) were prepared by modified spontaneous emulsification solvent diffusion (modified-SESD).The aim is to develop a new kind drug that is more stable, safe and effective. On the basis of the establishment of analytical method and choosing of nanoparticles prescription, the preparation of IVM-PLA-NPs was optimized by equality design. And the stability, safety, pharmacodynamics and pharmacokinetics were systemically studied.
Part 1: The preparation of Ivermectin poly lactic acid nanoparticles (IVM-PLA-NPs).The content of IVM is an index to the drug content of IVM-PLA-NPs, and the Ultraviolet analytical method on IVM-PLA-NPs was established to study recovery and accuracy and so on. Results show that IVM has the maximal absorption in 245 nm. The good linear range was 10~80μg/mL. The mean recovery is 97.87%. RSD of the recovery is 1.98%, the accuracies with-day and between-day are respectively lesss than 5% and 7%. There is high recovery, accuracy and repeatability by using the analysis method we established in this study and this method can be used in quality control research.
Part 2: The stability and quality evaluation on IVM-PLA-NPs. The characters were detected by electron microscope, photon correlation spectroscope, the viscosity statement, refraction and electric conductivity. Results show that the IVM-PLA-NPs was transparent spherical liquid, and its average diameter is (67.9±2.7) nm. Its term of validity can be predicted to be 25 months by long-term and the classical constant temperature experiment. The quality of IVM-PLA-NPs was stable. It conforms to the request of nanoparticles drug delivery system.
Part 3: The safety evaluation on IVM-PLA-NPs. Evaluate the safety of IVM-PLA-NPs by acute toxicity and cell toxicity experiment. Results show that the accumulation LD50 of mice by using IVM-PLA-NPs is 62.675mg/kg; The cell toxicity is level 1, not obviously toxic. IVM-PLA-NPs are safe and non-toxic.
Part 4: The pharmacodynamics evaluation on IVM-PLA-NPs.By using IVM-PLA-NPs of 5% and 10% especially, the effects of curing acarus on rabbits were evaluated. Results show that both IVM-PLA-NPs of 5% and 10% were good at curing curing acarus on rabbits Above all, the preparation of IVM-PLA-NPs is simple .And IVM-PLA-NPs are stable, safe and effective, according to the standards of nanoparticles and drug delivery.
试验一:伊维菌素聚乳酸纳米粒的制备。采用改良的自乳化溶剂扩散法制备伊维菌素聚乳酸纳米粒,以伊维菌素作为伊维菌素纳米粒含量测定的指标性成分,建立伊维菌素纳米粒的紫外分析方法,对其回收率、精密度等进行研究。结果表明,伊维菌素纳米粒在245nm处有最大吸收,在10~80μg/mL范围内线性关系良好,其平均回收率为97.87%。回收率的相对标准偏差(RSD)为3.05%、进样重复性的RSD为1.98%、日内精密度的RSD小于5%,日间精密度的RSD小于7%。本研究建立的分析方法回收率高、精密度和重复性良好,可满足其质量控制研究。
试验二:伊维菌素聚乳酸纳米粒的质量及稳定性评价。对利用透射电镜、激光粒度分布仪、黏度计、折光仪和电导仪等对其质量进行检测;通过离心、加速、光照、低温、长期和经典恒温加速试验对其稳定性进行评价。结果表明,制备的伊维菌素聚乳酸纳米粒为淡蓝色透亮均一的液体,其平均粒径为(67.9±2.7)nm;测出其有效期为25个月。本研究制备的伊维菌素聚乳酸纳米粒质量稳定。
试验三:伊维菌素聚乳酸纳米粒的毒性研究。通过急性毒性和细胞毒性试验对伊维菌素聚乳酸纳米粒的安全性进行评价。结果表明,伊维菌素聚乳酸纳米粒对小鼠的LD50为62.675mg/kg,是原料药组的2.67倍,属于无毒级;对细胞毒性为1级,无明显毒性。本研究制备的伊维菌素聚乳酸纳米粒安全无毒。试验四:伊维菌素聚乳酸纳米粒的药效对比试验。以低剂量和高剂量的伊维菌素聚乳酸纳米粒对自然感染螨虫的兔进行治疗试验,对其药效进行初步研究。结果表明,5%、10%的伊维菌素聚乳酸纳米粒对兔螨均有较好的疗效。表明伊维菌素纳米粒是一种有开发前景的抗寄生虫新制剂。本研究制备的伊维菌素聚乳酸纳米粒药效显著。
综上所述,伊维菌素聚乳酸纳米粒制备简单,稳定性高,安全性良好,药效显著,符合纳米粒的各种特性和用药要求。
In this research, by using the poly lactic acid (PLA) as carrier, Ivermectin poly lactic acid nanoparticles (IVM-PLA-NPs) were prepared by modified spontaneous emulsification solvent diffusion (modified-SESD).The aim is to develop a new kind drug that is more stable, safe and effective. On the basis of the establishment of analytical method and choosing of nanoparticles prescription, the preparation of IVM-PLA-NPs was optimized by equality design. And the stability, safety, pharmacodynamics and pharmacokinetics were systemically studied.
Part 1: The preparation of Ivermectin poly lactic acid nanoparticles (IVM-PLA-NPs).The content of IVM is an index to the drug content of IVM-PLA-NPs, and the Ultraviolet analytical method on IVM-PLA-NPs was established to study recovery and accuracy and so on. Results show that IVM has the maximal absorption in 245 nm. The good linear range was 10~80μg/mL. The mean recovery is 97.87%. RSD of the recovery is 1.98%, the accuracies with-day and between-day are respectively lesss than 5% and 7%. There is high recovery, accuracy and repeatability by using the analysis method we established in this study and this method can be used in quality control research.
Part 2: The stability and quality evaluation on IVM-PLA-NPs. The characters were detected by electron microscope, photon correlation spectroscope, the viscosity statement, refraction and electric conductivity. Results show that the IVM-PLA-NPs was transparent spherical liquid, and its average diameter is (67.9±2.7) nm. Its term of validity can be predicted to be 25 months by long-term and the classical constant temperature experiment. The quality of IVM-PLA-NPs was stable. It conforms to the request of nanoparticles drug delivery system.
Part 3: The safety evaluation on IVM-PLA-NPs. Evaluate the safety of IVM-PLA-NPs by acute toxicity and cell toxicity experiment. Results show that the accumulation LD50 of mice by using IVM-PLA-NPs is 62.675mg/kg; The cell toxicity is level 1, not obviously toxic. IVM-PLA-NPs are safe and non-toxic.
Part 4: The pharmacodynamics evaluation on IVM-PLA-NPs.By using IVM-PLA-NPs of 5% and 10% especially, the effects of curing acarus on rabbits were evaluated. Results show that both IVM-PLA-NPs of 5% and 10% were good at curing curing acarus on rabbits Above all, the preparation of IVM-PLA-NPs is simple .And IVM-PLA-NPs are stable, safe and effective, according to the standards of nanoparticles and drug delivery.
引文
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