抗凝治疗通常用于预防和治疗心血管疾病、脑血管疾病和癌症患者的动脉和静脉血栓。静脉血栓是继急性冠状动脉疾病和中风之后心血管死亡的第三大原因。迫切需要有效的抗凝治疗且出血风险最小。 Variegin 及其变体是一种新型抗凝血酶肽，在临床前研究中显示出有希望的结果。 Variegin 及其最佳变体 Ultravariegin (UV) 与肝素和比伐卢定等传统药物相比，可以更有效地抑制血栓形成，同时减少出血。然而，紫外线的寿命短仍然限制其在临床环境中的使用。聚乙二醇化是一种将聚乙二醇 (PEG) 链与肽或药物缀合的方法，可以通过延长紫外线在体内的循环时间来帮助提高紫外线的有效性。在本研究中，UV 使用马来酰亚胺-PEG5k 和 10k 进行聚乙二醇化。在体外和离体大鼠和兔血浆中评估了聚乙二醇化对 UV 抗凝血酶活性的影响，结果显示对功效的影响最小。对大鼠和兔子的体内研究表明，聚乙二醇化紫外线比未修饰的紫外线具有更长的半衰期和更强的抗凝血作用，特别是皮下注射时。聚乙二醇化显着延长了紫外线在兔子体内的半衰期，从而产生长达 4 天的持续抗凝作用。这表明增加紫外线的大小并用聚乙二醇屏蔽可以减少肾脏的清除并延长其循环时间。聚乙二醇化UV改善的半衰期和抗凝血酶活性使其成为抗凝治疗更有利的选择。

Anticoagulant therapy is commonly used to prevent and treat arterial and venous blood clots in patients with cardiovascular disease, cerebrovascular disease, and cancer. Venous blood clots are the third leading cause of cardiovascular death following acute coronary artery disease and stroke. There is a significant need for effective anticoagulant therapy with minimal risk of bleeding. Variegin and its variants are a new type of antithrombin peptide that has shown promising results in preclinical studies. Variegin and its best variant, ultravariegin (UV), can more effectively inhibit blood clot formation while causing less bleeding than traditional medications such as heparin and bivalirudin. However, the short lifespan of UV remains a limitation for its use in clinical settings. PEGylation, a method of conjugating poly(ethylene glycol) (PEG) chains to peptides or drugs, may help improve the effectiveness of UV by extending its circulation time in the body. In this study, UV was PEGylated using maleimide-PEG5k and 10k. The impact of PEGylation on the antithrombin activity of UV was assessed in vitro and ex vivo in rat and rabbit plasma, showing minimal effects on the efficacy. In vivo studies in rats and rabbits revealed that PEGylated UV had a longer half-life and greater anticoagulant effects than unmodified UV did, especially when it was administered subcutaneously. PEGylation significantly extended the half-life of UV in rabbits, resulting in sustained anticoagulant effects for up to 4 days. This demonstrated that increasing the size of UV and shielding it with PEG could reduce clearance by the kidneys and prolong its circulation time. The improved half-life and antithrombin activity of PEGylated UV make it a more favorable choice for anticoagulant therapy.