Injection preparation of human interleukin 10-Fc fusion protein

Abstract

The invention relates to the field of biological medicines, and particularly provides an injection preparation of human interleukin 10-Fc fusion protein. The injection preparation comprises human interleukin 10-Fc fusion protein, buffer salt, a protein protective agent, an isoosmotic adjusting agent and a nonionic surfactant, wherein the pH value of the preparation is 5.0-6.0. The injection preparation provided by the invention has the advantages of better stability, simple preparation process, low cost, no need of special equipment and harsh conditions, easiness in large-scale production and the like. The human interleukin 10-Fc fusion protein in the preparation is formed by fusing the human interleukin 10 and the Fc part of the immunoglobulin IgG through the connecting peptide, so that the half-life period of the human interleukin 10 in a living body is prolonged, the stability of the human interleukin 10 in the body is improved, and the application of the human interleukin 10 to disease treatment is facilitated.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to an injection preparation of human interleukin 10-Fc fusion protein. Background technique [0002] Interleukin-10 (IL-10) is a cytokine discovered in 1989. Since its discovery, many studies have deeply analyzed the biological characteristics of this cytokine. Human IL-10 is a 35KD dimer, which is composed of two monomers combined by non-covalent bonds. There are two disulfide bonds in the monomer to maintain the structure and biological activity of the factor. Disruption of the non-covalent interactions of the body subunits becomes biologically inactive. [0003] IL-10 is a multi-cellular cytokine (expressed by macrophages, monocytes, T cells, B cells, NK cells, DC cells and mast cells, etc.), multifunctional and pleiotropic, regulating cell The growth and differentiation of CKD are involved in inflammatory and immune responses, and are currently recognized inflammatory and ...

AI Technical Summary

Problems solved by technology

However, the half-life of recombinant human IL-10 in the body is only 2 hours, and it will be cleared soon, which will seriously affect its application in disease treatment. In order to overcome the short half-life of recombinant human IL-10, some research institutions currently use The PEGylation method prolongs its half-life in vivo, but there are many PEGylation sites, and the product of human IL-10 after PEGylation is not uniform, which brings great difficulties to the production process and quality control

At the same time, some researchers have begun to study human interleukin 10-Fc fusion protein, but the structural design of human interleukin 10-Fc fusion protein, appropriate dosage, production process and quality control will face huge challenges. To date, no human IL-10-Fc fusion protein is in clinical development

[0006] In addition, like most protein molecules, human interleukin 10-Fc fusion protein is unstable and will undergo various chemical and physical degradations, especially the high-level structure of human interleukin 10-Fc fusion protein is very fragile. Conformational changes are prone to occur during transportation, storage and use, such as denaturation, aggregation and precipitation. These degradation and aggregation products will have a great impact on the safety of biopharmaceuticals, especially some protein aggregates can stimulate human immunity In mild cases, the efficacy of biological drugs will be reduced, and in severe cases, it may even cause the death of patients

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