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A combination inhibitor and application of a new type of liver withered or inferior to nano -drug particles

A technology for combining inhibitors and nano-drugs, which is applied in the directions of drug combinations, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc., can solve problems such as increasing drug efficacy, reduce toxic and side effects, and easily obtain reagents. , to achieve the effect of drug efficacy

Active Publication Date: 2019-10-01
BEIJING OBSTETRICS & GYNECOLOGY HOSPITAL CAPITAL MEDICAL UNIV +2
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AI Technical Summary

Problems solved by technology

On the basis of previous research, the inventors simultaneously applied inflammatory cytokines and phagocytic pathway inhibitors to prevent FPA / EPI from being phagocytized by liver KC cells, so as to realize long-term circulation of nanoparticles in the body, increase drug efficacy, and reduce toxic and side effects. Evasion of immune cell phagocytosis provides a scientific basis, the above research has not seen any literature or patent reports

Method used

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  • A combination inhibitor and application of a new type of liver withered or inferior to nano -drug particles
  • A combination inhibitor and application of a new type of liver withered or inferior to nano -drug particles
  • A combination inhibitor and application of a new type of liver withered or inferior to nano -drug particles

Examples

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Embodiment 1

[0041] [Example 1] Simultaneous inhibition of KC cell secretion of inflammatory factors from NF-kB signaling pathway and phagocytosis pathway

[0042] Extract the primary KC according to the reference, culture the cells for 48 hours, digest with 0.25% trypsin / EDTA, adjust the cell density and inoculate in a 96-well plate, at 37°C, 5% CO 2 Culture in an incubator. When the cell fully adheres to the wall and reaches 80% fusion rate, the medium is discarded and the inhibitor is added. The dose of the inhibitor is as follows: chlorpromazine (CPZ) 7 μg / mL, amiloride (AMR) 50 μM / mL mL, nystatin (NY) 50 μg / mL, tetrahydropyrrole dithiocarbamate (pyrrolidinedithiocarbamate, PDTC) 10 μM / mL. Incubate at 37°C for 24h, discard the inhibitor solution and wash 3 times with PBS, add FPA / EPI nanoparticle suspension (prepared according to reference 20), incubate at 37°C for 2h, take 100ul of the supernatant from each well and add it to the microtiter plate. ELISA kit instructions to measure cy...

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Abstract

The invention relates to a novel inhibitor composition for phagocytosis of nano-drug particles by liver Kuppfer cells and an application of the inhibitor composition to nano-drugs. The inhibitor composition comprises an effective dose of an inflammatory cell factor inhibitor and a phagocytosis pathway inhibitor, wherein the phagocytosis pathway inhibitor includes one or more of the following inhibitors: a macropinocytosis inhibitor, a pinocytosis inhibitor, a clathrin-dependent endocytosis inhibitor, a caveolin-dependent endocytosis inhibitor and an actin-dependent phagocytosis pathway inhibitor; and the inflammatory cell factor inhibitor includes one or more of the following inhibitors: an NF-kB signal channel specific inhibitor and other inflammatory cell factor inhibitors. The nano-drugs subjected to phagocytosis by the liver KCs (Kuppfer Cells) can be reduced expectedly, so that the circulation time of the nano-drugs in bodies is prolonged, the drug effect is better achieved, and the toxic and side effects are reduced; and therefore, the inhibitor composition has a clinical application prospect.

Description

technical field [0001] The invention relates to a novel hepatic Kuppfer cell phagocytosis nano drug particle inhibitor composition and its application in nano medicine. Background technique [0002] After most nano-scale drug delivery systems (Nano-scale Drug Delivery System, NDDS) enter the body, while achieving drug efficacy and reducing toxic and side effects, the in vivo mononuclear phagocyte system (Mononuclear Phagocyte System, MPS) mainly includes liver Kupffer cells (Kupffer Cell, KC) and spleen giant cells will cause a large number of nanoparticles to accumulate in non-target tissues, especially the liver and spleen (references [1-2]), which not only greatly reduces the distribution of drugs in target tissues, but also greatly reduces the It may cause corresponding organ toxicity, which limits the application of targeted drug carriers. How to reduce the clearance of drug-loaded nanoparticles by mononuclear phagocytosis systems such as the liver and achieve more eff...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61K31/4965A61K31/5415A61K31/7048A61P43/00A61K31/704A61K47/36A61K9/14A61P35/00A61K31/40
Inventor 唐红波冯欣代荫梅郏亚静蒋子雯陈红丽周志敏张其清
Owner BEIJING OBSTETRICS & GYNECOLOGY HOSPITAL CAPITAL MEDICAL UNIV
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