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A hyaluronic acid nanomicelle targeting hepatic stellate cells, its preparation method and application

A technology of hepatic stellate cells and nanomicelles, which is applied to medical preparations with non-active ingredients, medical preparations containing active ingredients, and pharmaceutical formulas, etc., which can solve the problem of poor specificity and the inability to ensure that drugs are targeted to diseased liver cells and other issues, to achieve the effect of strong specificity, good safety and biocompatibility, and wide application

Active Publication Date: 2020-09-08
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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  • A hyaluronic acid nanomicelle targeting hepatic stellate cells, its preparation method and application
  • A hyaluronic acid nanomicelle targeting hepatic stellate cells, its preparation method and application
  • A hyaluronic acid nanomicelle targeting hepatic stellate cells, its preparation method and application

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Using ethylenediamine as a connecting 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%. Dissolve 23mg of phospholipid E80, 31mg of sodium deoxycholate, 7mg of HA-deoxycholic acid conjugate, and 4mg of silibinin in ethanol in a round-bottomed flask, rotatively evaporate to form a film, add normal saline to hydrate, and obtain HA-loaded Drug nano micelles, 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%. Dissolve 25mg of phospholipid S100, 25mg of sodium deoxycholate, 6mg of HA-deoxycholic acid conjugate and 3mg of pirfenidone in acetone and place in a round-bottomed flask, rotary evaporate to form a film, add deionized water for hydration, and obtain HA Drug-loaded nano micelles with a particle size of 35nm.

Embodiment 3

[0070] Using ethylenediamine as a connecting bridge, the hydrophobic deoxycholic acid was connected to the carboxyl group of the side chain of HA (molecular weight 6kDa) through amide reaction to prepare HA-deoxycholic acid coupling with a modification degree of 7.0%. Dissolve 25mg of phospholipid S45, 75mg of sodium deoxycholate, 5mg of HA-deoxycholic acid conjugate, and 6mg of vitamin E in a round-bottomed flask in methanol, rotatively evaporate to form a film, add 5% glucose solution for hydration, and obtain HA-loaded Drug nano micelles, 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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Patent Type & Authority Patents(China)
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