Preparation And Application Of Altrenogest Inclusion Complex Based On Cyclodextrin And Its Derivatives

Altrenogest（ALT）is an unnatural progesterone that regulates estrus in animals at the same time.It is insoluble in water.In order to improve its solubility,β-cyclodextrin（β-CD）and its derivative hydroxypropyl β-cyclodextrin（HP-β-CD）is used as the main body of the inclusion compound,and ALT is used as the guest of the inclusion compound to prepare two kinds of inclusion compounds.Then select the ALT-β-CD inclusion compound with higher ALT content and inclusion rate,prepare the inclusion compound slow-release silicone suppository,and put it into use,which is conducive to the realization of standardized intensive breeding and reduce the labor force caused in the production process And loss of production costs.1.Preparation of ALT-β-CD inclusion complexThe ALT wavelength was determined to be 352 nm after scanning,and an ALT standard curve was established.Using the saturated solution method and orthogonal test,the optimal preparation process conditions of the ALT-β-CD inclusion compound were obtained: the molar ratio of the feed was 1:3,and the mixture was heated and stirred at 65 ℃ for 3 h.The average drug content in the ALT-β-CD inclusion compound was（9.06±0.257）%,the average inclusion rate was（78.70±2.674）%,and the average recovery rates were 85.09%,89.71%,and95.07%,respectively.After identification by circular dichroism scanning,it can be known that ALT has been successfully included,and the prepared ALT-β-CD inclusion complex solution is stable within 10 h.2.Preparation of ALT-HP-β-CD inclusion complexUsing the freeze-drying method and orthogonal test,the optimal preparation process conditions for obtaining the ALT-HP-β-CD inclusion compound are: the molar ratio of the feed is 1:6,and the mixture is heated and stirred at 55 ℃ for 4 h.The average content of ALT in the ALT-HP-β-CD inclusion compound was（2.74±0.093）%,the average inclusion rate was（65.89±3.225）%,and the average recovery rates were 87.10%,90.46% and 90.05%,respectively..After identification by circular dichroism scanning,it can be known that ALT has been successfully included,and the prepared ALT-HP-β-CD inclusion complex solution is stable within 10 h.3.Sustained-release determination of ALT inclusion complex sustained-release preparation in vitroThe ALT-β-CD inclusion compound and medical silica gel were mixed and matured to prepare ALT-β-CD inclusion compound sustained-release silicone suppository,which was subjected to a 20-day in vitro sustained release test.The results showed that in the 20-day in vitro sustained-release test,the concentration of ALT released showed an overall increasing trend,and slightly decreased at 4 days,and then showed an upward trend until 20 days,and the ALT release rate was faster than 24 hours after 24 hours.It is inferred that the stable release time of ALT in ALT-β-CD inclusion compound sustained-release silicone suppositories can reach more than 20 days,which meets the requirements for the sustained release duration of actual production and use,so the next animal sustained-release test can be performed.4.ALT inclusion complex sustained-release preparation in vivo extended release assayThe pregnancy rate of sows fed with ALT oral solution mixed feed was 84.1%,and the sow pregnancy rate was 91.7% when the self-made ALT-β-CD inclusion compound silicone suppository sustained-release device was used.The results showed that the gestation rate of sows using ALT-β-CD inclusion complex sustained-release silicone suppositories was higher than that of ALT oral solution,which was in line with the original expectation,and could be used as a estrus preparation at the same time.