A kind of glomerulus-targeted protein nanoparticle pharmaceutical composition and its application

Abstract

The invention provides a glomerulus-targeted protein nanoparticle pharmaceutical composition and an application thereof. The protein nanoparticle pharmaceutical composition is mainly prepared from a protein ingredient, a pharmacological active substance and a stabilizer, and the grain size of the protein nanoparticle pharmaceutical composition ranges from 10nm to 170nm. With the application of the pharmaceutical composition, passive targeted drug delivery of glomerular mesangial cells is achieved, and the aggregation concentration of a drug in a glomerulus is obviously improved or the aggregation duration of the drug in the glomerulus is prolonged, so that the curative effect of the drug is remarkably improved, and meanwhile, the toxic and side effects of the drug on a non-targeted part are greatly reduced.

Description

technical field [0001] The invention relates to a glomerulus-targeted protein nanoparticle pharmaceutical composition and a preparation method and application thereof, belonging to the technical field of medicine. Background technique [0002] Glomerular diseases, including primary and secondary glomerulonephritis, are the main causes of chronic renal failure and end-stage renal disease, and are seriously threatening human health. According to statistics, in my country, glomerular diseases account for 54.4% of the causes of end-stage renal disease, of which glomerulonephritis accounts for 48.1%. Most glomerular diseases are immune-mediated inflammatory diseases. Therefore, immunomodulatory therapy is an important means for the treatment of immune-mediated glomerular inflammatory diseases. Currently, glucocorticoids and immunosuppressants are the main treatments in clinical practice. However, these two drugs have obvious side effects, such as femoral head necrosis and Cushin...

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Problems solved by technology

[0005] The prior art document CN103690957A discloses a glomerulus-targeted microparticle drug delivery system and its preparation method, although it successfully constructs the kidney glomerulus after modifying the microparticles (liposomes, nanoparticles, micelles) with PEGylated amidines. Ball-targeted microparticle drug delivery system, but there are still many deficiencies in the prior art: first, the prepared microparticle drug delivery system is a cationic microparticle drug delivery system, and there is a risk of in vivo toxicity. A large number of literature reports have confirmed that as a carrier Cationic liposome itself can produce strong cytotoxicity to various cells, and the higher the charge, the greater the toxicity. Obviously, this microparticle drug delivery system has certain defects in safety, which is not conducive to clinical drug use; secondly, this The composition of the microparticle drug delivery system is complicated, the preparation process is cumbersome, and the preparation cost is high, and it is not yet possible for industrialized mass production

Obviously, the protein nanoparticles prepared by this traditional method have poor biodegradability and high toxicity, especially the residual organic solvents such as glutaraldehyde will cause the inactivation of biologically active macromolecules and increase the risk of toxic side effects in the body

Moreover, this method is cumbersome and complicated, and takes a long time, especially the cross-linking curing takes more than 24 hours, and the time cost is high

In summary, the applicant believes that it is not feasible to apply the tripterine pharmaceutical composition with albumin as a pharmaceutical carrier to the glomerulus-targeted drug delivery system

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