| Transdermal delivery, a new delivery stlye, is a research focus in home and abroad for its easy delivery, no first pass effect on liver and eliminating adverse reactions. Subcutaneous injection of ivermectin can be used to birds’ ectoparasite, Ivermectin do not dissolve in water, administered through drinking water is difficult,but it is not suited for pigeon to mix ivermectin into the pigeon’s unprocessed.To prepare a transdermal agent for pigeon, Chinese medicinal menthol and borneol are compared in promoting transdermal for ivermectin, and filter a best transdermal concentration, which can be the basis for transdermal agent preparation. On this basis, therapeutic effect are observed, and analysis the Pharmacokinetics characteristics in pigeon’s body due to ivermectin in transdermal enhancer.Test one. Screening of Chinese Medicine Transdermal Enhancers To screen the best concentration for transdermal enhancers, pigeon’s skin was cut and a2-chamber diffusion cell was adopted. Then work out the accumulated permeation and percolation coefficient within12h through comparing the absorbed dose of ivermectin for borneo of1%-5%with menthol. The result shows that the best concentration for t borneo and menthol are4%. The accumulated permeation of menthol of4%is higher than that of borneo in12h. The same conclusion could also draw from percolation coefficient. So, it can be concluded from the test that the best concentration for menthol is4%.Test two. transdermal agent’s preparation and safety test First, determine the best process for making transdermal agent, then carry on preliminary appraisal in this foundation. An orthogonal test is arranged as per L9(34) orthogonal test table, with polyvinyl alcohol-124(PVA-124), glycerol and sodium carboxymethylcellulose (CMC-Na) of1%as three factors. And give a total quality score with film forming ability and appearance. The result shows that transdermal agent made of1.5g PVA-124,6mL glycerin,4M1CMC-Na of1%and menthol of4%in Test one is of good film forming ability and safety. Different effect on film forming time of every factors:PVA-124> glycerin>1%CMC-Na. Different effect on film forming appearance of every factors:1%CMC-Na> PVA-124>glycerin. Different effect on total quality score of every factors:PVA-124>1%CMC-Na>glycerin. PVA-124has the biggest influence on transdermal agent’s quality, while glycerin has the least one.Test three. The influence of the keratodermia structure after transdermal delivery In order to investigate the variation of keratodermia tissue of the mice and rabbits after delivering the self-made transdermal agent. The depilation parts of mice and rabbits were smeared with the self-made transdermal agent in the test, then the tissue section of mice skins were observed after1h,3h,6h, and observed that of rabbits10h later. Results display that the permutation of keratodermia of mice gradually become loosened and rumpled, and the cavitations in keratodermia increase with the time. Results on rabbits showed that if menthol acted on keratodermia for long time, the keratodermia then dropped off and separated away from skins epithelial. In the test, keratodermia in solvent group arrayed loosely, permutation of keratodermia wholly behaved like ribbon with the time until the changes of keratodermia stopped. The cavitations in keratodermia are helpful to the raise of ventilation property. Medication is able to keep away from keratodermia with the whole shedding of keratodermia. In this way, medication can enter skin and be absorbed. Result display that the menthol promotes the transdermal absorption of the drug molecules by destroyying keratodermia.Test four. Observe the transdermal agent curative effects on pigeons with biting lice of poultry infected. The test evaluated the transdermal agent curative effects on pigeons with biting lice of poultry infected. The sicken pigeons were randomly allocated to the blank and the drug. The drug of2mL transdermal agent was administered on crop, and Observe the transdermal agent curative effects on pigeons after24h,48h and72h. The result showed part of sicken pigeons began to recovery. Cure rate of sicken pigeons was73.33%after24h,91%after48h,94%after72h. water and feed was not affected, and no adverse reaction was found during experimental period. The result showed that self-made transdermal agent provide a new preparations for pigeons with biting lice of poultry infected, which has a good anthelminthic effect.Test five. Pharmacokinetics of ivermectin within transdermal agent in pigeon’s body The test studied Pharmacokinetics of ivermectin within transdermal agent in pigeon’s body. After transdermal delivery, measured the48H plasma concentration of ivermectin with LC-MS/MS, and analysis kinetic parameter with winnonlin6.2.0non-compartment model. The result showed that peak plasma concentration Cmax is34.93ng/mL, and peak time is6h, elimination half-lives of drug in blood t1/2is39.30h. The result showed that ivermectin within transdermal agent can pass through the skin and into blood streams, and can maintains a level of plasma concentration. |
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