申请人:Max-Planck-Gesellschaft zur Förderung der
Wissenschaften e.V.
公开号:EP3834848A1
公开(公告)日:2021-06-16
The present invention relates to conjugates of amphotericin B and gold nanoparticles stabilized with thiohexoses or thiopentoses, and a method to produce said nanoparticles. As the conjugates of amphotericin B to the stabilized gold nanoparticles show several advantages over amphotericin B alone, the present invention is also directed to pharmaceutical compositions comprising said nanoparticles, and to their use for treat fungal and leishmanial infection. These amphotericin B stabilized gold nanoparticles are dispersible in water and are not toxic for mammalian cells differently from free amphotericin B and other currently used amphotericin B preparations. Importantly, the conjugates of amphotericin B and stabilized gold nanoparticles are more efficacious in treating all forms of Cryptococcal infections (planktonic, intracellular and biofilms) than amphotericin B. Additionally, the conjugates are more effective against extracellular and intracellular forms of Leishmania mexicana and Leishmania major. Therefore, amphotericin B conjugated to thiohexose or thiopentose stabilized gold nanoparticles offer safer and better treatment option than free amphotericin B, and in particular for Cryptococcal and Leishmanial infections.
本发明涉及两性霉素 B 和用硫代己酮或硫代戊酮稳定的金纳米颗粒的共轭物,以及生产所述纳米颗粒的方法。与单独使用两性霉素 B 相比,两性霉素 B 与稳定金纳米颗粒的共轭物显示出多种优势,因此本发明还涉及包含上述纳米颗粒的药物组合物,以及它们在治疗真菌和利什曼病感染方面的用途。这些两性霉素 B 稳定金纳米粒子可在水中分散,与游离两性霉素 B 和其他目前使用的两性霉素 B 制剂不同,对哺乳动物细胞无毒性。重要的是,两性霉素 B 和稳定金纳米粒子的共轭物在治疗各种形式的隐球菌感染(浮游、细胞内和生物膜)方面比两性霉素 B 更有效。因此,与游离两性霉素 B 相比,两性霉素 B 与硫代己糖或硫代戊糖稳定金纳米粒子共轭可提供更安全、更好的治疗选择,尤其是对隐球菌和利什曼菌感染。