This invention pertains to disulfide-linked conjugates of therapeutic agents containing at least one thioamide group with polymer comprising at least one thiol group, so as to provide a controlled release pharmaceutical composition for administration to animals for the prophylaxis or treatment of various conditions or diseases. The therapeutic agent conjugate may comprise an inactive or weakly active prodrug form which may be converted into the original therapeutic compound by the natural action of reducing agents in vivo. The composition may comprise a mixture of polymers each with a different thioamide-containing agent attached, or a polymer conjugated with a mixture of thioamide-containing agents. Modified properties of the therapeutic compound potentially provided by the polymer itself, as well as by other compounds also appended to the polymer, include but are not limited to greater water solubility, longer in-vivo half-life (due to larger size of the conjugate), slower release from a sustained-release depot (due to larger size of the conjugate), better oral bioavailability and tissue-specific targeting.
本发明涉及含有至少一个
硫酰胺基团的治疗剂与至少一个巯基的聚合物形成的二
硫键结合物,以提供用于预防或治疗动物各种疾病或病症的控制释放药物组合物。治疗剂共轭物可以包含一个不活性或弱活性的前药形式,可以通过体内还原剂的自然作用转化为原始的治疗化合物。该组合物可以由具有不同
硫酰胺含量的代理附着的聚合物混合物或与一组
硫酰胺含量的代理结合的聚合物组成。聚合物本身以及附加到聚合物的其他化合物可能提供的治疗化合物的改性特性包括但不限于更大的
水溶性,更长的体内半衰期(由于共轭物的大小更大),从持续释放沉积物中缓慢释放(由于共轭物的大小更大),更好的口服
生物利用度和组织特异性靶向。