| Acute pain within 72 hours after surgery is a key factor affecting the quality of patients’ recovery.The local anesthetic ropivacaine has the characteristics of low toxicity and separation of motor nerve block and is widely used in clinical postoperative analgesia,but its analgesic time can not meet the needs of some patients.Multivesicular liposomes have a good sustainedrelease effect due to the structure of the internal non-concentric chambers.In this paper,a ropivacaine hydrochloride multivesicular liposome has been prepared,which has a good sustained-release effect and has a long-term analgesic effect.There is huge application value.Ropivacaine(Rpv)is a long-acting local anesthetic with the characteristics of low nerve and cardiotoxicity,separation of nerve block and motor block,and is widely used in clinical practice.This thesis intends to screen out the best production process conditions through single factor experiment and orthogonal experiment to prepare long-acting sustained-release analgesic preparations of ropivacaine hydrochloride multivesicular liposomes(Rpv-MVLs),and to explore its release in vitro.,Neurotoxicity and pharmacodynamic behavior.On this basis,RpvMVLs were innovatively modified and improved,and sodium alginate modified ropivacaine hydrochloride multivesicular liposomes(Rpv-MVLs-Alg)and chitosan temperature-controlled hydrocoagulation were prepared.Gum multivesicular liposomes(Rpv-CS-MVLs).The main research contents of this paper are as follows:(1)Single factor optimization of each factor in the preparation process of Rpv-MVLs.In this paper,the final encapsulation efficiency and morphology results of Rpv-MVLs were used as indicators,and the 9 influencing factors in the preparation process of Rpv-MVLs were initially optimized and screened.(2)Orthogonal experimental analysis of various factors in the preparation process of RpvMVLs.The 9 influencing factors in the preparation process of Rpv-MVLs in this thesis are divided into preparation process factors and prescription process factors,and orthogonal optimization design has been carried out respectively.Like the single factor experiment,the encapsulation efficiency and morphology results are also selected as evaluation indicators,but the morphology results are subjectively scored and quantified,and the best combination of factors for preparing Rpv-MVLs is finally obtained through orthogonal analysis.(3)Explore the toxic effects of Rpv-MVLs on nerve cells.This paper is divided into three experiments to illustrate the effect of Rpv-MVLs on neuronal toxicity,including the effect of Rpv-MVLs on cell proliferation activity,the effect on intracellular ROS and the effect on cell apoptosis.The results clearly show that Rpv-MVLs has lower neurocytotoxicity than Rpv.Under the same drug concentration,the Rpv-MVLs(88.89%,72.04%,64.54%)group has the effect of 1d,3d,and 5d.The cell proliferation rate was higher than that of the Rpv group(88.75%,65.97%,54.16%),the ROS of the Rpv-MVLs group(55.10)was also lower than that of the Rpv group(62.55),and the cells in the Rpv-MVLs group(21.96%)The apoptosis rate was also significantly lower than that of the Rpv group(25.22%).(4)Explore the pharmacodynamic behavior of Rpv-MVLs.This dissertation explores the pharmacodynamic behavior of Rpv-MVLs by establishing a nerve block model in SD rats.The nerve block time of the Rpv-MVLs group for rats can reach 6-8h,which is much higher than the 2-4h of the Rpv solution group,indicating that Rpv-MVLs has a very obvious sustainedrelease effect.(5)The preparation of ropivacaine hydrochloride multivesicular liposomes(Rpv-MVLsAlg)modified by sodium alginate was explored.In this paper,nano-calcium carbonate is mixed with liquid paraffin in advance,so that the sodium alginate gel can be evenly coated on the surface of Rpv-MVLs.In addition,this paper also compared the stability and in vitro release behavior of Rpv-MVLs-Alg and Rpv-MVLs,and found that the physical stability of RpvMVLs-Alg within one month is much higher than that of Rpv-MVLs.In the investigation of the in vitro release behavior of Rpv-MVLs-Alg,it was found that it significantly alleviated the original sudden release phenomenon of Rpv-MVLs.The cumulative release rate was reduced from 80% to 60% during the 12 h release time,which improved the release rate.Interpretation effect.(6)Explore the preparation of chitosan hydrogel multivesicular liposomes(Rpv-CSMVLs).In this chapter,for the first time,a temperature-sensitive hydrogel is encapsulated in the multivesicular cavity of a multivesicular liposome.From the results of in vitro release,RpvCS-MVLs does have a more significant sustained release effect than Rpv-MVLs,and it presents an obvious two-step ladder.Rpv-MVLs only needs 12 hours to release 80% of the total drug amount,while Rpv-CS-MVLs can release 80% of the total drug amount for up to 48 hours,which indicates that Rpv-CS-MVLs significantly improves the sustained release of Rpv-MVLs effect.In general,this article has prepared a long-acting sustained-release ropivacaine hydrochloride polycystic lipid with a certain sustained-release effect,lower toxicity to nerve cells,and good pharmacodynamic behavior through systemic process optimization.Plastid preparations.Rpv-MVLs-Alg and Rpv-CS-MVLs obtained by improving the structure of RpvMVLs on this basis have a significant improvement in the slow-release effect,and both have very large research value and application prospects. |
