The Preparation Of Brucine Patch And Its Site-specific Analgesia And Delivery

Brucine,an indole alkaloids,is one of the main active ingredient of Strychnos.Brucine has been proved to have good central analgesic effect as well as excellent peripheral analgesic anti-inflammatory effect.Another indole alkaloid named strychnine also exists in Strychnos,which is higher content and more toxic than brucine,and has no analgesic and anti-inflammatory effect.Therefore,it’s of great significance to separate brucine from the total alkaloid.Brucine has a strong analgesic activity,but it is also a toxic component.The peak concentration is reached within half an hour when taken orally,thus the poisoning symptom is easy to appear.In order to develop a safer and more effective brucine preparation for local soft tissue inflammation,this paper studied a more energy-saving and more environmentally-friendly technology to extract and separate brucine from semen nux vomica,then designed the preparation of brucine patch,finally conduct a preliminary study about the analgesic efficacy and pharmacokinetics mechanism of the brucine patches.An energy-saving and environmentally-friendly technology of brucine extracting and separating from semen nux vomica is like this,brucine powder is extracted twice,the first time use 10 times amount of 60 % ethanol to flash eatract for 2 min,and the second time was 10 times amount to flash for 1 min.The extract was then concentrated and added20 % sodium hydroxide to tune into alkalinity as sample solution.D101 macroporous resin was selected,adding 10 BV of the sample solution at 2 BV/h speed.Then washed with distilled water to the effluent colorless or close to colorless.Finally,70% ethanol was used to elute at 2 BV/h with the usage was 6 BV.After purifying and refining,the final purity of brucine reach 87.2%.In this study,Franz vertical diffusion cell was used in vitro transdermal experiment.The effects of type of pressure-sensitive adhesives(PSAs)and penetration enhancers as well as its usage on percutaneous penetration of brucine were investigated with the invitro penetration rate of brucine as the main index.Optimal formulation of brucine transdermal patch is 7-4302 silicone PSA added with 2.5% lauric acid,3% nitroxone and2% brucine,the percutaneous flow rate of the patch was 3.02 μg/cm2/h,and the cumulative amount of brucine within 24 hours was 77.08 μg/cm2.The brucine transdermal patch developed in this paper can not effectively inhibit the pain caused by hot plate in mice abdomen,but it can resist the abdominal pain caused by acetic acid,and the analgesic effect was better than oral administration ofbrucine.The concentration of drug in the skin of mice in patch group was found significantly higher than the oral group,but the plasma concentration was lower than that in the oral group when analysis of drug concentration in plasma and skin tissue.The results indicated that the local delivery of the drug exits,and drug was more accumulated in the local than absorbed into the systemic circulation,thus caused no significant increase in plasma concentration.The patches prepared in this paper has a good therapeutic effect on local patients and will not produce central toxicity.