Rapamycins are novel triene macrolide compounds produced by Streptomyces hygroscopicus (Vezina C, et al, J. Antibiot, 1975, 10: 721-726.) or Actinoplane sp. (Nakao K, et al, EP022446, Nov. 11, 1993). Typical rapamycin compounds mainly include Sirolimus, Everolimus, Temsirolimus and the like, which have the structures as follows:

Rapamycin compounds were initially found to have antifungal activities, particularly a relative high inhibitory activity against Candida albicans. 
Lately, it was found that rapamycin compounds are inhibitors for mammalian target of rapamycin (mTOR), and can act as immunodepressants. The immunosuppressive effect and the effect for preventing immune rejection after organ transplantation of the rapamycin compounds are first disclosed in the FASEB Journal (3, 3411, 1989). The action mechanism is to block the signal transduction via different cytokine receptors, so as to block the progression of G1-S phase transition of T leukomonocytes and other cells, thereby exerting an immunosuppressive effect.
Rapamycin compounds have been approved to be used in the treatment of multiple indications of tumors on clinic. For example, everolimus has been approved by FDA for the treatment of solid tumors such as advanced breast cancer, renal cell carcinoma, pancreatic cancer, angiomyolipoma and the like. Rapamycin compounds were also proved to be effective in the treatment models of diseases such as multiple sclerosis, rheumatoid arthritis, anemia and other diseases (Can J. Physiol. Pharmcol. 1997, 55, 48-52). And rapamycin was also reported to have a certain potential effect on prolonging the life cycle of mammals (Harrison D E, et al, Nature, 2009, 460, 392-395).
Rapamycin compounds can be used in multiple indications and have great application value in the clinical treatment. However, owing to the poor water-solubility as well as the poor stability in vivo, the absorption of the rapamycin compounds in vivo is low and so is the bioavailability, which is only 15%-30% (Guy Jerusalem, et al, Breast Cancer Research and Treatment, 2010, 125:2447-2455). And the administration of rapamycin compounds in a relatively large dosage would bring about more side effects.
In view of the above situation, enhancing the water-solubility of the rapamycin compounds can enhance their bioavailability and improve their therapeutic effect on related diseases to a great extent.
Polypeptide is an endogenous substance in human body. It consists of several amino acids and has a relatively good water solubility and an extensive bioactivity. Combination of polypeptide with a small molecule drug can enhance the solubility of the small molecule drug in one aspect, and can achieve in vivo targeted release and sustained release or improve the bioactivity with the help of the polypeptide in another aspect. For example, glutathione is a common endogenous polypeptide. It consists of glutamic acid, cysteine and glycine. Glutamic acid contains mercapto groups and has antioxidative and integrated antidotal effects. Glutathione is also a nutriment for cell growth. It can be easily taken in by cells, especially by tumor cells which propagate rapidly. A complex which prepared by the coupling of glutathione and a small molecule drug very likely has a selectivity for tumor cells which propagate rapidly and can reduce the toxicity of the anti-tumor drugs to normal cells in human body to some extent and achieve the targeted release of the small molecule drug simultaneously. In addition, glutathione is a water-soluble tripeptide. When it forms a complex with a small molecule drug, the water solubility of the small molecule drug can be improved to a great extent.