Abstract

1. The UPLC-MS/MS method was established with good precision, accuracy and stability to determine the concentrations of TPL in biological samples, such as heart, liver, spleen, lung, kidney, plasma and joint.

2. After being made into microspheres, TPL can stay in the joint tissue for a long time, further reducing the number of times joint cavity administration, and its sustained release effect was significantly improved compared with the solution dosage form.

3. The pharmacokinetic parameters, such as AUC_(0–t), AUC_(0–∞), T_1/2, T_max, MTR_(0–t), and MTR_(0–∞) of the TPL-PLGA-MS group were significantly increased compared with those of the solution group. The microsphere preparation could significantly slow the release rate of the drug from the joint cavity.

4. TPL-PLGA-MS can significantly reduce the expression of inflammatory factors such as IL-1, IL-6, TNF-α and hs-CRP. TPL-PLGA-MS for articular cavity injection has potential as a new preparation for the treatment of RA.

摘要

1. 建立了具有良好的精密度，准确性和稳定性的UPLC-MS / MS方法，可测定心脏，肝脏，脾脏，肺，肾，血浆和关节等生物样品中TPL的浓度。

2. 制成微球后，TPL可以在关节组织中停留很长时间，从而进一步减少了关节腔给药的次数，与溶液剂型相比，TPL的缓释作用得到了显着改善。

3. TPL-PLGA-MS组的药代动力学参数，例如AUC _（0–t），AUC _{（0–∞）}，T _1/2，T _max，MTR _（0–t）和MTR _{（0–∞）}与溶液组相比显着增加。微球制剂可以显着减慢药物从关节腔的释放速度。

4. TPL-PLGA-MS可显着降低炎症因子如IL-1，IL-6，TNF-α和hs-CRP的表达。用于关节腔注射的TPL-PLGA-MS有潜力作为治疗RA的新制剂。