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Hepatic stellate cell targeted hyaluronic acid nano-micelle, preparation method and application thereof

A hepatic stellate cell and nanomicelle technology is applied in the directions of non-active ingredients medical preparations, active ingredients containing medical preparations, pharmaceutical formulas, etc. and other issues, to achieve the effect of good safety and biocompatibility, strong specificity and significant therapeutic effect

Active Publication Date: 2018-03-30
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Third, many drug delivery systems for the treatment of liver diseases have poor specificity, and it is impossible to ensure that the drugs are selectively targeted to diseased liver cells
[0006] To sum up, there is currently no HSCs-targeted preparation on the market that is effective in treating liver fibrosis, liver cirrhosis, and other liver diseases with good safety and industrialization.

Method used

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  • Hepatic stellate cell targeted hyaluronic acid nano-micelle, preparation method and application thereof
  • Hepatic stellate cell targeted hyaluronic acid nano-micelle, preparation method and application thereof
  • Hepatic stellate cell targeted hyaluronic acid nano-micelle, preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1

[0066] Using ethylenediamine as a bridge, the hydrophobic deoxycholic acid was connected to the carboxyl group of the side chain of HA (molecular weight 100kDa) through an amide reaction to prepare a HA-deoxycholic acid conjugate with a modification degree of 9.4%. 23mg of phospholipid E80, 31mg of sodium deoxycholate, 7mg of HA-deoxycholic acid conjugate and 4mg of silibinin were dissolved in ethanol, placed in a round-bottomed flask, rotary evaporated to form a film, and hydrated by adding physiological saline to obtain HA drug loading Nanomicelle, particle size 42nm.

Embodiment 2

[0068] Using ethylenediamine as a linking bridge, the hydrophobic deoxycholic acid was connected to the carboxyl group of the side chain of HA (molecular weight 300kDa) through an amide reaction to prepare a HA-deoxycholic acid conjugate with a modification degree of 10.1%. 25mg of phospholipid S100, 25mg of sodium deoxycholate, 6mg of HA-deoxycholic acid conjugate and 3mg of pirfenidone were dissolved in acetone and placed in a round-bottomed flask, rotary evaporated to form a film, and deionized water was added for hydration to obtain HA Drug-loaded nanomicelles with a particle size of 35nm.

Embodiment 3

[0070] Using ethylenediamine as a bridge, the hydrophobic deoxycholic acid was connected to the carboxyl group of the side chain of HA (molecular weight 6kDa) through an amide reaction to prepare a HA-deoxycholic acid conjugate with a modification degree of 7.0%. 25mg of phospholipid S45, 75mg of sodium deoxycholate, 5mg of HA-deoxycholic acid conjugate and 6mg of vitamin E were dissolved in methanol and placed in a round-bottomed flask, rotary evaporated to form a film, and 5% glucose solution was added for hydration to obtain HA drug loading Nanomicelle, particle size 80nm.

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Abstract

The invention provides a hepatic stellate cell targeted hyaluronic acid nano-micelle, a preparation method and application thereof. The nano-micelle can encapsulate antifibrosis drugs and treat hepatic stellate cell lesion caused liver diseases, like hepatic fibrosis, liver cirrhosis and the like, has the advantages of small particle size (less than 100nm), good specificity, high hepatic stellatecell targeting efficiency, obvious anti-hepatic fibrosis function in vivo and in vivo and the like, and has broad application prospects.

Description

technical field [0001] The invention relates to a hyaluronic acid nano-micelle capable of targeting hepatic stellate cells, a preparation method and application thereof, and belongs to the field of pharmaceuticals. Background technique [0002] The liver is a very important organ of the human body, composed of hepatic parenchymal cells (HPCs, about 60-70%) and non-parenchymal cells (about 30-40%). Among them, non-parenchymal cells mainly include macrophages, Kupffer cells, hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs), immune cells and other non-parenchymal cells. As the largest solid organ in the human body, the liver has many physiological functions, such as removing foreign substances, metabolizing drugs, filtering blood and producing proteins such as albumin. Among them, nonparenchymal cells play a key role in liver function, although their numbers are so small. For example, Kupffer cells are a kind of macrophages with strong phagocytic acti...

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K47/36A61P1/16A61P35/00A61K31/357A61K31/4418A61K31/355A61K31/7076
CPCA61K9/1075A61K31/355A61K31/357A61K31/4418A61K31/7076A61K47/36
Inventor 龚涛李文浩周楚楚张志荣宋旭孙逊
Owner SICHUAN UNIV
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