Natural light induced controlled release drug as well as preparation method and application thereof

A technology of controlled release of drugs and natural light, applied in the directions of drug combination, drug delivery, pharmaceutical formulation, etc., can solve the problems of destroying the balance of blood vessels, increasing the degree of tumor malignancy, and deteriorating the tumor microenvironment, achieving delayed release time and inhibiting tumors. Growth, improve the effect of curative effect

Active Publication Date: 2020-09-15
NANTONG UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The growth of solid tumors is closely related to the formation of tumor blood vessels. The relative hypoxia caused by the rapid proliferation of tumor cells makes the tumor tissue continue to produce pro-angiogenic factors, which destroys the original state of blood vessel balance, resulting in obvious tumor blood vessels. Heterogeneity, which worsens the tumor microenvironment, increases tumor malignancy and reduces therapeutic efficacy

Method used

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  • Natural light induced controlled release drug as well as preparation method and application thereof
  • Natural light induced controlled release drug as well as preparation method and application thereof
  • Natural light induced controlled release drug as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] The preparation process of Endo-ICG-ERM of the present invention:

[0043] Such as figure 1 As shown, first extract the red blood cell membrane, take 1mL whole blood, add 10mL hypotonic solution (70mOsm / kg), and lyse at 4°C for 20-30 minutes; centrifuge at 2000rpm for 5min, wash with hypotonic solution 3 times, and wash with isotonic PBS The solution was washed 3 times to obtain red blood cell membrane solution (about 50 μL); then ICG was dissolved in PBS solution, Endo was diluted in PBS, the concentrations of ICG solution and Endo solution were both 10 mg / mL, and the pH of the solution was adjusted to 7.4; followed by ultrasound for drug entrapment on erythrocyte membrane, mix the prepared ICG solution and Endo solution in equal proportions at a volume ratio of 1:1, mix the solution and erythrocyte membrane fluid (mix according to the following ratio: 1mL of whole blood extracted erythrocyte membrane mixed with 1mL ICG solution and 1mL Endo solution, that is, the ini...

Embodiment 2

[0047] The effect of different concentrations of Endo solution on the release of Endo in vivo:

[0048] From Figure 5 It can be seen from the figure that the entrapment capacity of Endo on the red blood cell membrane is related to the initial concentration of Endo, the greater the initial concentration of Endo, the greater the entrapment capacity of Endo on the erythrocyte membrane. When the concentration is increased to 25.0mg / mL, and the entrapment time (ultrasound) exceeds 6 minutes, the entrapment efficiency does not increase significantly.

[0049] From Figure 6It can be seen that the effective release time of Endo also increases with the increase of the initial concentration of Endo, and when the concentration increases to 20.0mg / mL, the release time exceeds 4 days; when the concentration increases to 25.0mg / mL, The release time did not increase significantly.

[0050] Therefore, considering cost-effectiveness, Endo adopts an initial concentration of 20.0mg / mL and a...

Embodiment 3

[0052] The effect of loading different concentrations of ICG solutions on the release of Endo:

[0053] Weigh a certain amount of ICG powder and dissolve it in PBS solution, so that the concentration of ICG solution is gradient to carry out experiments, which are 2mg / mL, 6mg / mL, 10mg / mL, 14mg / mL respectively, and at the same time, use Na 2 HPO 4 and KH 2 PO 4 Adjust the pH to 7.4; dilute Endo with PBS solution to a certain concentration (40.0mg / mL), and adjust the pH to 7.4; mix ICG solution, 1mL of Endo solution and 1mL of ERM solution (red blood cell membrane fluid) extracted from whole blood evenly , sonicated for 6 minutes, and placed at 37° C. for 30 minutes to prepare Endo-ICG-ERM.

[0054] The ICG solution was prepared according to a certain concentration gradient (that is, the initial concentrations of ICG in the above-mentioned entrapment solution were 1 mg / mL, 3 mg / mL, 5 mg / mL, and 7 mg / mL), and the Endo-ICG-ERM drug was prepared, and its exposure to natural light...

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Abstract

The invention discloses a natural light induced controlled release drug. The natural light induced controlled release drug adopts erythrocyte membranes to encapsulate Endo and ICG, wherein when the erythrocyte membranes are encapsulated, the initial concentration of the Endo is 5.0-25.0mg / mL, the initial concentration of the ICG is 1.0-7.0mg / mL, and each milliliter of an encapsulating solution contains 0.5mL of the erythrocyte membranes extracted from whole blood. According to the natural light induced controlled release drug, the release amount of the Endo is associated with natural light photography, so that controlled release can be effectively realized, and good blood concentration is maintained.

Description

technical field [0001] The invention relates to a novel controlled-release drug of Endo. Background technique [0002] Indocyanine green (ICG) can produce a large amount of singlet oxygen ( 1 [O2]) and its metabolite hydrogen peroxide (H 2 o 2 ) increases and accumulates, which will destroy the phospholipid bilayer of the erythrocyte membrane, open the pore of the erythrocyte membrane, and release the drug contained therein, thereby completing ICG-responsive drug release; when light irradiation stops, singlet oxygen, etc. The amount released is also reduced, the membrane pores are closed, and drug release ceases. [0003] The growth of solid tumors is closely related to the formation of tumor blood vessels. The relative hypoxia caused by the rapid proliferation of tumor cells makes the tumor tissue continue to produce pro-angiogenic factors, which destroys the original state of blood vessel balance, resulting in obvious tumor blood vessels. Heterogeneity, which worsens t...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K9/50A61K47/46A61K38/17A61P35/00
CPCA61K41/0057A61P35/00A61K9/5068A61K9/0009A61K41/0042A61K38/1709A61K2300/00
Inventor 夏栋林黄好陈超顾海鹰鲍鸿一王乡儿
Owner NANTONG UNIVERSITY
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