Fatty-acid-binding alhumin-drug nanoparticle lyophilized preparation and preparation method thereof

Abstract

The invention discloses a fatty-acid-binding alhumin-drug nanoparticle lyophilized preparation and a preparation method thereof; by use of high affinity and stable binding characteristics of fatty acids and albumin specific sites, nanoparticles using the fatty acids as the core are prepared under the effects of high shearing forces, one or a plurality of ''water-insoluble'' or ''water-soluble '' drug in the form of ''solution'' or ''ultrafine nanoparticles'' is / are ''packaged'' or ''bound'' to obtain various types of nanoparticles suspensions, and the lyophilized preparation is obtained by removal of organic solvent, sterilization and drying. The fatty-acid-binding alhumin-drug nanoparticle lyophilized preparation is composed only by albumin, the drugs and the fatty acids, does not contain any accessories, and has the biological properties of high nanoparticles integrity and stability in a in vitro solution and in vivo blood circulation, , significant increase of drug content in gp60-rich receptor cells or tumor tissues, significant improvement of the LD50 (half lethal dose) and MTD (maximum tolerated dose) of load drugs, close of antigen sites of ''packaged'' or ''bound'' proteins, and the like.

Description

technical field [0001] The invention relates to a nanoparticle freeze-dried preparation and a preparation method, in particular to a fatty acid-binding albumin-drug nanoparticle freeze-dried preparation and a preparation method, belonging to the technical field of medicine preparation. Background technique [0002] Human serum albumin (Human Serum Albumin, referred to as HSA) is the main protein in human plasma, is a non-glycosylated protein, consists of 585 amino acids, and has a molecular weight of 66kD. The concentration of HSA in the plasma of healthy people is 35-55g / L, and the half-life is about 19 days. HSA plays an important role in maintaining blood colloid osmotic pressure, amino acid and energy metabolism of tissue cells, and transport of fat-soluble substances such as bilirubin, fatty acids and drugs. HSA has sufficient sources, can be extracted from human blood, and can also be produced by genetic recombination technology. HSA is non-toxic, non-immunogenic, and...

AI Technical Summary

Problems solved by technology

Specific antibody fusion to PE38 can significantly improve the anti-tumor targeting, but it cannot effectively avoid the antigenicity of PE38 toxin and its damage to vascular endothelial cells, resulting in severe toxicity, especially vascular leak syndrome ⑨

Therefore, for PE toxins and other molecules and drugs that can cause severe toxic side effects in the blood circulation, it is not enough to improve the affinity of antibodies and / or reduce the antigenicity of PE38 toxins only through the optimization of amino acid sequences

The applicant unexpectedly found that the combination of HSA and PE38 can effectively "block" the antigenic site of PE38, and it is believed that the damage of PE38 toxin to the human vascular endothelial system will also be reduced; and the targeting of tumor tissue by albumin nanoparticles and The enrichment effect and the use of the transmembrane mechanism of HSA and fatty acids in the local tumor to achieve the specific killing of PE38 on tumor tissue is a new treatment strategy, and no similar reports have been found after searching

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