Study On The Immune Active Peptide Thymosin α1 Analogue

Immune active peptide is a kind of polypeptide and cell signaling substance exist in organism immune function. It can stimulate the body lymphocyte value, enhance the phagocytosis of macrophage, improve the ability of organism to resist external pathogen infection, reduce the incidence of the body, and has anti-tumor function.Thymalfasin(Tα1) is a kind of immune active peptide composed of 28 amino acid residues. It is the one of the strongest component of the active peptidesin animal thymosin, and its molecular weight is 3108. It can make the mature T cells and the NK cells secrete a variety of lymphatic factor, such as interleukin Ⅱ(IL-2), γ-interferon(γ-IFN), and prompte high affinity interleukin Ⅱ receptor(IL-2R) generated. Tα1 is mainly applied in malignant tumor, immunodeficiency disease, autoimmune diseases and the treatment of chronic infection in the clinical.Although Tα1 is a very good immune active peptide, but it has significant limitations in clinical because of its poor enzyme stability. So it is very important to improve the stability of peptide drug metabolism. It is an important part of the study of peptide drug development by modifying peptides sequence, increase the resistance to enzymatic hydrolysis stability, and maintain or enhance the activity of the peptide. This topic is the study of the β amino acid modification to replace and modified peptide drugs, known as beta peptide.β-peptide can be folded into a certain secondary structureas the α-peptide in nature, such as screw, folding and Angle, and it has the similar biological activity with the corresponding α-peptide, because they have the similar chemical structures. β-peptide occupies an important position in the field of drug design, it can resist the degradation of biological enzyme in the body, particularity of the converting enzyme and the peptide enzyme. Beta peptide can prolong the drug half-life in vivo and improve its bioavailability because of its good enzyme stabilities.The research content of this paper is the preparation of Tα1 simulation contain β-amino acids(hereinafter referred to as STα1) research. STα1 is an immune active peptide synthesized by solid consistent method, and contains 28 amino acids. STα1 has the basis structure of the Tα1 and has beta amino acid substitution, because we use beta-X to replace the 2, 6, 14, 20 amino acids in order to increase its stability in enzyme solution. This paper is a study of STα1 preparation prescription, determination of biological activities of agents, and Tα1 as the reference to evaluate the preliminary pharmacodynamics of its preparation.We studied the STα1’s freeze-dried preparation with reference to the literature, the research content include the consist of excipients, pH and buffer system. By evaluating the relevant matter content change on different prescription, we finally determine the formulation of dextran and sucrose as excipient, citric acid, sodium citrate buffer as buffer salt, and pH 6.0 ~ 7.5. STα1 may store more than one year stably in cold storage conditions use his prescription.We study the STα1 activity with a rosette experiments in vitro in comparison with Tα1 reference substance, the results confirmed that STα1 is obviously better than the low concentration range at Tα1, and the best concentration of STα1(1.5 ug/ml) is a quarter of the best concentration of Tα1(6.25 ug/ml).STα1 has obvious inhibitory effect on tumor to adjuvant chemotherapy drugs(cisplatin) in preliminary pharmacodynamics research, in the Netherlands on lewis lung cancer model in mice, this embodies in inhibitory rate. Further data show that STα1 is based on spleen coefficient and immune factor influences of CD4+/CD8+. Experiments prove that STα1is effective in mice lewis lung cancer treatment of cisplatin resistance. The results of this paper provided reference for other peptide drug development.The results of this paper provided reference for other peptide drug development, and laid a solid foundation for independent intellectual property rights for class 1 new drug STα1 development.