Application of rhamnolipid in preparation of anti-fibrosis medicinal preparation

An anti-fibrosis and pharmaceutical preparation technology, applied in the intersection of surface chemistry and medicine, can solve the problem that rhamnolipid specifically inhibits myofibroblasts, etc., to help autonomous repair, relieve advanced fibrosis, prevent The effect of interrupting the fibrosis process

Inactive Publication Date: 2016-02-17
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] So far, there have been no reports of rhamnolipids specifically inhibiting myofibroblasts, and accordingly no rhamnolipids have been used as anti-fibrotic drugs

Method used

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  • Application of rhamnolipid in preparation of anti-fibrosis medicinal preparation
  • Application of rhamnolipid in preparation of anti-fibrosis medicinal preparation
  • Application of rhamnolipid in preparation of anti-fibrosis medicinal preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] Example 1: Double rhamnolipids have specific cytotoxicity to myofibroblasts induced by TGF-β1 from lung epithelial cells.

[0018] In the serum-free suspension culture of lung epithelial cells A549 (the medium used is DMEM low-glucose medium, containing L-glutamine 2mM, penicillin 100U / mL and streptomycin 100μg / mL), TGF-β1 was used to induce myogenic growth. Fibroblasts, which expressed the characteristic α-SMA protein by fluorescent immunostaining and western blotting. Add the obtained myofibroblasts and lung epithelial fibroblasts into the medium containing 10mg / Kg double rhamnolipid, and observe the morphological changes of these two kinds of cells within 24h by microscope, as shown in figure 2 As shown, the lung epithelial A549 cells did not show any morphological changes during this period, while the myofibroblasts showed membrane bubbles in 10 hours, indicating that the plasma membrane of the cells had completely detached from the actin-rich cortical cytoskeleton...

Embodiment 2

[0019] Example 2: Monorhamnolipid has specific cytotoxicity to human fibroblasts and their induced myofibroblasts

[0020] From foreskin human fibroblasts and their successfully transformed myofibroblasts, 5×10 4 The density of cells / mL was inoculated in a 24-well plate. After the cells adhered to the wall, the medium was replaced with 0.1% FBS medium containing different concentrations of monorhamnolipid for 24 hours and then lactate dehydrogenase (LDH) was used. represents cell activity. The medium treated with rhamnolipids was collected to measure the extracellular LDH value, and the culture plate was washed with PBS, and then the intracellular solution was collected after the cells were disrupted by Triton X-100 to determine the intracellular LDH value. The extracellular and intracellular LDH values ​​were measured using kits, and the LDH leakage rate was obtained by calculating the percentage of LDH in the medium to the total intracellular and extracellular LDH. Then, a...

Embodiment 3

[0024] Example 3: Double rhamnolipid inhibits the contractile function of myofibroblasts to collagen gel

[0025] Same as in Embodiment 2, the fibroblasts are transformed into myofibroblasts through induction. The two kinds of cells were cultured with collagen gel (1mg / mL) respectively, and the culture medium containing 0, 10, and 30 mg / kg of double rhamnolipid was investigated, and the shrinkage ability of collagen after 2 days of culture was observed. It was found that without the action of rhamnolipids, the shrinkage ability of myofibroblasts was significantly higher than that of fibroblasts, and the shrinkage rate of collagen gel blocks increased from 17% to about 35%. After 10 and 30mg / kg rhamnolipids, the collagen shrinkage ability of fibroblasts was not affected, but the collagen shrinkage ratio of myofibroblasts decreased from 35% to 22%, which was close to the shrinkage of fibroblast gel blocks ratio.

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Abstract

The invention discloses application of rhamnolipid in the preparation of an anti-fibrosis medicinal preparation. Rhamnolipid serves as a biological surface active agent, myofibroblast causing fibrillation can be selectively killed, and thus the fibrillation of tissues or organs is inhibited. The preparation prepared by adopting the rhamnolipid acts on fibrosis animal models, so that the fibrosis process can be obviously retarded to assist organ repair. Moreover, an external application ointment containing the rhamnolipid can inhibit skin fibrosis appearing in skin healing of burned patients. The new application of the rhamnolipid lays the foundation that the rhamnolipid is developed into novel anti-fibrosis medicine.

Description

technical field [0001] The invention belongs to the cross field of surface chemistry and medicine, and relates to the application of rhamnolipid in the preparation of anti-fibrosis pharmaceutical preparations. Background technique [0002] Rhamnolipid is a glycolipid biosurfactant produced by Pseudomonas species (Pseudomonasspp), which is composed of rhamnosyl and β-hydroxy fatty acid in the form of covalent bonds. Its molecular structure is as follows: figure 1 shown. [0003] Rhamnolipids have numerous applications. For example, in the petroleum industry, rhamnolipids can be used for crude oil recovery, crude oil transportation and tertiary oil recovery, etc. In the field of environmental remediation, the application research of rhamnolipids includes chelating heavy metal ions and degrading insoluble organic matter. In the cosmetic industry, rhamnolipids are used as insect repellants, antacids, anti-dandruff detergents, contact lens solutions, deodorants, and toothpaste...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7024A61P43/00
CPCA61K31/7024
Inventor 孟琴沈冲
Owner ZHEJIANG UNIV
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