Abstract: ²²⁵Ac is one of the most promising and highly anticipated alpha therapeutic isotopes in the field of nuclear medicine. Currently, more than 30 ²²⁵Ac targeted isotope drugs have entered clinical trials stages Ⅰ-Ⅲ worldwide. The ²²⁹Th/²²⁵Ac generator is currently the main production route for ²²⁵Ac. Due to the very small global stock of ²²⁹Th, the annual output of ²²⁵Ac is less than 2 Ci. The production of ²²⁵Ac through the irradiation of ²²⁶Ra faces challenges including target material shortages, difficulties in re-extraction, and radiation protection issues associated with ²²⁶Ra decay daughters. Thorium target materials have the characteristics of high fission cross-section, relatively abundant content, low price, easy processing, and good thermodynamic properties. Using high-energy proton accelerators to irradiate thorium targets is one of the main feasible ways for commercial preparation of ²²⁵Ac in major laboratories internationally. The research team collaborates with Liu Zhibo’s team from Peking University in 2021 to complete the first domestic μCi level ²²⁵Ac targeting and purification experiment. In order to achieve Curie level engineering production and application of ²²⁵Ac, it is necessary to ensure sufficient batch production of ²²⁵Ac while minimizing the content of ²²⁷Ac (half-life 21.77 a). Therefore, the selection of energy and irradiation time for accelerator irradiation of thorium targets is a crucial factor. The study focuses on the variation of the ²²⁷Ac/²²⁵Ac activity ratio within the 50-200 MeV irradiation energy range. Simulation results indicate that the 50-69 MeV energy region represents a peak production window for ²²⁵Ac concurrently with a trough for ²²⁷Ac, establishing it as an ideal interval for ²²⁵Ac production. Specifically, irradiation within the 54-69 MeV range enables the production of curie-level quantities of ²²⁵Ac while minimizing the ²²⁷Ac impurity to less than 0.1%. This result indicates that a 75 MeV proton cyclotron can be used for large-scale production of ²²⁵Ac. Utilizing this energy for production can not only reduce accelerator costs, but also obtain ²²⁵Ac with sufficient yield and low ²²⁷Ac proportion. According to the calculation results, a separation and purification simulation experiment was carried out, using La instead of Ac, and successfully separating high-purity lanthanum from the simulated target liquid through a three-stage resin column series process, with a La recovery rate of 78.60%. The loss is primarily attributed to physical adsorption and dead volume retention during the multi-stage separation process; The chemical purity is 87.18%, with the main residual impurities being light rare earth elements such as Sm, Y, and Pr. The remaining elements are primarily lanthanides, which can be completely separated from ²²⁵Ac in the actual process, achieving high radionuclidic purity that meets the requirements for medical use in terms of stable supply. Based on theoretical calculations of ²²⁵Ac yield and its proportion, as well as simulation studies of separation and purification processes, this study can provides a reference for subsequent experiments on the preparation of ²²⁵Ac from thorium targets irradiated by medium to high energy proton accelerators.