Anti-fibrosis medicine nanometer preparation and preparation method thereof

An anti-fibrosis, nano-preparation technology, applied in drug combinations, pharmaceutical formulations, digestive system, etc., can solve the problems of targeted absorption of nano-preparations, failure to be tried and verified, affecting drug treatment effects, etc., to achieve high-efficiency anti-hepatic Fibrotic drug delivery, efficient liver fibrosis treatment, and the effect of improving availability

Active Publication Date: 2018-07-13
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, in the process of liver fibrosis, a large amount of fibrotic collagen accumulates in the extracellular matrix to form scar tissue, which hinders the exchange of substances and will inevitably hinder the targeted absorption of nano-preparations and affect the therapeutic effect of drugs.
There is also a large amount of fibrotic collagen and hyaluronic acid accumulation in the tumor microenvironment. In order

Method used

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  • Anti-fibrosis medicine nanometer preparation and preparation method thereof
  • Anti-fibrosis medicine nanometer preparation and preparation method thereof
  • Anti-fibrosis medicine nanometer preparation and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Embodiment 1 Synthesis and preparation of nano-preparation components, such as figure 1 Shown:

[0052] 1. Synthesis of MAL-PEG-VA and SH-PEG-VA

[0053] Weigh 100 mg of MAL-PEG-NHS or SH-PEG-NHS and dissolve in 5 mL of DMSO solution, weigh 22.5 mg of vitamin A and dissolve in the above solution, under dark conditions, stir and react overnight, dialyze out the DMSO solution, The unreacted vitamin A was removed by micromembrane filtration, and then freeze-dried for later use.

[0054] 2. Thiolated Collagenase I

[0055] Weigh 100 mg type I collagenase and 2.75 mg 2-iminothiolane hydrochloride, dissolve them in 5 mL 0.01M phosphate buffer, react at room temperature for 1 h, and place on a Sephadex column (G -25) Desalting and purification, UV (280 nm) detection of protein concentration in the purified solution, set aside.

[0056] 3. Preparation of drug-loaded PLGA-PEG-MAL nanoparticles

[0057] Polymer nanoparticles loaded with anti-fibrotic drugs or fluorescent dye...

Embodiment 2

[0062] Example 2 The investigation of the safety of nano preparation carrier material

[0063] The cytotoxicity of PP, PPR, PPC and PPCR empty vectors to various liver cells (L02, LX2 and HSC-T6) was determined by MTT method. The specific operation steps are as follows: first, the cells in the logarithmic growth phase were added to 96-well plates , the plating density per well is 1×10 4 / 200 μL, cultured in a cell culture incubator for 24 h. Then use FBS-free medium to dilute the PP, PPR, PPC and PPCR empty vector groups into a series of concentration gradients, and use the cells that are not given materials as the control group, and the cells that only add medium to the blank wells as the blank group. The drug concentrations administered to the cells were 5, 10, 20, 50, 100 μg / mL, respectively. Aspirate the medium in the 96-well plate, then add 100 μL of samples with different concentration gradients to each well, and repeat 5 wells for each concentration. Continue to cu...

Embodiment 3

[0065] Example 3 Quantitative analysis of uptake of coated coumarin 6 nanometer preparation by flow cytometry in LX2 and L02 cells

[0066] Nano-preparations of PP / coumarin 6, PPR / coumarin 6, PPC / coumarin 6 and PPCR / coumarin 6 were prepared as described in Example 1. The LX2 and L02 cells were divided into 1 × 10 5 / 1mL inoculated in a 24-well plate, grown adherently in a 5% CO2 cell culture incubator at 37 °C for 24 h, sucked off the medium, and added 500 μL of free coumarin 6, PP / coumarin 6, PPR / coumarin 6, PPC / coumarin 6, and PPCR / coumarin 6 serum-free medium solutions, each group was provided with three auxiliary wells, and the concentration of coumarin 6 contained was 0.025 mg / mL Uniform standards. Continue to culture for 6 hours, wash with PBS three times, digest with trypsin, centrifuge at 2000 rpm to pellet the cells, resuspend the cells in serum-free medium, and quantitatively detect the uptake of coumarin 6 by flow cytometry.

[0067] The cell uptake data measu...

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Abstract

The invention discloses a high-efficiency targeted type anti-fibrosis medicine nanometer preparation and a preparation method thereof, and relates to a collagenase and/or vitamin A-modified nanometerpreparation or a carrier thereof. The high-efficiency targeted type anti-fibrosis medicine nanometer preparation is characterized in that firstly, collagenase penetrates through a fibrosis collagen carrier; hepatic stellate cells are specifically targeted by the vitamin A, so that an anti-hepatic fibrosis medicine can be transferred in a targeted way at high efficiency, thereby reaching the purpose of high-efficiency hepatic fibrosis therapy. The high-efficiency targeted type anti-fibrosis medicine nanometer preparation has the advantage that the substance exchange barrier caused by accumulation of excessive collagen in the hepatic fibrosis process is overcome by the collagenase-modified nanometer preparation for the first time, so as to provide a novel way and strategy for the high-efficient transfer of the anti-hepatic fibrosis medicine.

Description

technical field [0001] The invention relates to an anti-fibrosis drug nano-preparation, in particular to the preparation and application of a hepatic stellate cell-targeted anti-fibrosis drug nano-preparation. Background technique [0002] Liver fibrosis and cirrhosis are one of the major chronic diseases that threaten human health. When the liver is continuously injured, the inflammatory factors secreted by various liver cells will promote the activation of hepatic stellate cells. After activation, hepatic stellate cells will secrete a large amount of fibrotic collagen to repair the damage. At the same time, the matrix metalloproteinase secreted by hepatic stellate cells The reduction of the amount of fibrotic collagen leads to a large accumulation of fibrotic collagen in the extracellular matrix, forming liver fibrosis, and the further deterioration of liver fibrosis will develop into liver cirrhosis. [0003] Due to the role played by hepatic stellate cells in the proces...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/506A61K47/69A61K47/64A61K47/60A61K47/54A61P1/16
CPCA61K31/506A61K45/00
Inventor 姜虎林邢磊范倩倩
Owner CHINA PHARM UNIV
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