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Nano preparation loaded with anti-pulmonary fibrosis medicament and immunomodulator and preparation method thereof

An immunomodulator and pulmonary fibrosis technology, which is applied in the field of nano-preparation and its preparation, can solve the problem of lack of effective therapeutic drugs or treatment systems for pulmonary fibrosis of nano-preparation, and achieve inhibition of fibroblast activation, reduction of collagen secretion, The effect of prolonging the cycle time

Active Publication Date: 2019-10-18
燃点(南京)生物医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Although nano-preparation has received more and more attention in the treatment of diseases, there is still a lack of effective therapeutic drugs or therapeutic systems for the treatment of pulmonary fibrosis.

Method used

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  • Nano preparation loaded with anti-pulmonary fibrosis medicament and immunomodulator and preparation method thereof
  • Nano preparation loaded with anti-pulmonary fibrosis medicament and immunomodulator and preparation method thereof
  • Nano preparation loaded with anti-pulmonary fibrosis medicament and immunomodulator and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Embodiment 1 Synthesis and preparation of nano-preparation components, such as figure 1 Shown is a schematic flow chart for the preparation of DPZ / MN nano-preparations, each preparation feeding such as figure 2 Shown:

[0062] 1. Preparation of nanoparticles containing DSPE-PEG-MAL, soybean lecithin (PC), and cholesterol containing sensitive peptide DPZ loaded with double drugs

[0063] 1. Preparation of sensitive peptide DPZ-loaded double-drug nanoparticles

[0064] First, the anti-hydrophobic pulmonary fibrosis drug M, X-PEG-MAL, phospholipid Y, sensitive peptide DPZ and cholesterol are dissolved in an organic solvent and mixed. The hydrophilic drug N was dissolved in the water phase, and the nanoparticles loaded with anti-pulmonary fibrosis drugs and immunomodulators were prepared by the film dispersion method; the MMP-2 in the liposome could realize the rapid release of the drug in the fibrotic microenvironment , so that the drug can take effect quickly to achie...

Embodiment 2

[0101] Example 2 The release of nano-preparations under the condition of high expression of MMP-2

[0102] Prepare DPZ / (nintedanib / colchicine), DPZ / (nintedanib), DPZ / (colchicine), DP / (nintedanib / colchicine) according to the method described in Example 1 , DP / (nintedanib), DP / (colchicine) nano preparations. After the nano-preparation was concentrated to 500 μL, 10 μg / mL MMP-2 matrix enzyme was added, and then placed at 37 ºC for 24 h, the particle size analyzer was used to measure the drug release rate of the nano-preparation under the condition of high MMP-2 expression.

[0103] (1) The MMP-2 matrix enzyme was added to the nano-preparation containing MMP-2, the nano-preparation without MMP-2, the nano-preparation containing MMP-2, and the nano-preparation containing MMP-2 were not tested by ultraviolet spectrophotometer. The nano-preparation with MMP-2 matrix enzyme and colchicine were scanned at the full wavelength of 200nm-800nm ​​to investigate the drug release rate under ...

Embodiment 3

[0105] Example 3 Using coumarin 6 as a model drug to investigate the escape ability of nano-preparations in primary fibroblasts

[0106] Nanoformulations of DP / coumarin 6 were prepared as described in Example 1. Primary fibroblasts were divided into 2 × 10 4 / mL inoculated in a confocal culture dish at 37 °C, 5% C0 2 After 24 h of adherent growth in the cell culture incubator, the culture medium was sucked off, and 1 mL (10 μg / mL) of coumarin 6 nanometer preparation was added, and incubated with fibroblasts for 30 min, 1 h, and 4 h, respectively. Wash three times with PBS, add cell fixative and incubate for 10 min, then wash three times with PBS. Then add lysotraker red lysosomal dye, at 37°C, 5% CO 2 After staining for 30 min under the conditions of , and washing with PBS for three times, the escape of nano-preparations in primary fibroblasts at different time points was measured using laser confocal (LSM-700).

[0107] The nano-preparation lysosome escape measured in th...

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Abstract

The invention discloses a nano preparation loaded with an anti-pulmonary fibrosis medicament and an immunomodulator and a preparation method thereof. The nanometer preparation is loaded with the anti-pulmonary fibrosis medicament and the immunomodulator at the same time, and the two medicaments are adopted to synergistically regulate and control the pulmonary fibrosis microenvironment to achieve the purpose of strengthening pulmonary fibrosis treatment through immunomodulation. Additionally, a nano preparation modified by a metalloproteinase-2(MMP-2) specific sensitive peptide segment and a carrier of the nano preparation are utilized to realize rapid massive release of therapeutic medicaments including the immunomodulator and the anti-pulmonary fibrosis medicament by means of the MMP-2 specific sensitive peptide segment, and therefore a new way and strategy for strengthening the treatment of pulmonary fibrosis are provided.

Description

technical field [0001] The invention discloses a nano-preparation loaded with anti-pulmonary fibrosis drugs and immune regulators and a preparation method thereof. Background technique [0002] Pulmonary fibrosis is a progressive interstitial lung disease with a high mortality rate, and the survival period is 3-5 years. In recent years, with the in-depth research, it has been discovered that the occurrence and progression of pulmonary fibrosis is closely related to the excessive activation of the immune system. When AT2 is damaged, damaged or apoptotic epithelial cells secrete a large amount of inflammatory factors and peroxides to recruit bone marrow-derived immune cells to migrate to the injured lung. At this time, a large number of immune cells accumulate in the lungs, proliferate and secrete pro-inflammatory factors to activate fibroblasts to transform into myofibroblasts. The activated myofibroblasts will secrete excess collagen to fill the damaged parts of the alveoli...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/24A61K47/42A61K45/06A61K31/496A61K31/165A61P37/02A61P11/00
CPCA61K9/1271A61K31/165A61K31/496A61K45/06A61K47/24A61K47/42A61P11/00A61P37/02A61K2300/00
Inventor 姜虎林常鑫林伊君邢磊
Owner 燃点(南京)生物医药科技有限公司
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