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Modified hyaluronic acid based macromolecule lipidosome and preparation method thereof

A hyaluronic acid and polymer technology, applied in the pharmaceutical field, can solve the problems of easy leakage of encapsulated drugs, poor biocompatibility, poor physical and chemical stability, etc., and achieve the effects of short preparation cycle, good stability and low cost

Inactive Publication Date: 2014-01-15
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, traditional liposomes are usually composed of small phospholipid molecules, which have some limitations. For example, the natural lecithin constituting the liposome membrane is easily hydrolyzed, has poor physical and chemical stability, and is difficult to store for a long time. At the same time, the encapsulated drug is easy to leak and cause burst release; In addition, traditional liposomes have disadvantages such as few functional groups, difficulty in surface modification, and single function.
The recent emergence of polymer liposomes has effectively solved some of the shortcomings of traditional liposomes, but most existing polymer liposomes often have higher cytotoxicity and poor biocompatibility due to the problems of the materials themselves.

Method used

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  • Modified hyaluronic acid based macromolecule lipidosome and preparation method thereof
  • Modified hyaluronic acid based macromolecule lipidosome and preparation method thereof
  • Modified hyaluronic acid based macromolecule lipidosome and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0029] Synthesis of stearic acid-modified hyaluronic acid. Take 1 g of hyaluronic acid with a molecular weight of 10,000 and 5 g of stearic acid into a beaker, add 12 mL of water, 36 ml of dimethyl sulfoxide, 1 g of EDC and 0.05 g of DMAP into the flask, stir magnetically, and react for 3 hours. After the reaction, put the product into a dialysis bag with a molecular weight of 8000-14000 for dialysis for 3 days, and freeze-dry to obtain stearic acid-modified hyaluronic acid. Such as figure 1 Infrared analysis test results show that 3430cm -1 The broad peaks on the left and right are multiple absorption peaks formed by the overlapping of stretching vibrations of -OH and -COOH in the hyaluronic acid structure, 2918, 2848cm -1 for—CH 3 , and—CH 2 The stretching vibration absorption peak of , 1080.11cm -1 The peak is the stretching vibration absorption peak of —C—O—C— in the ester bond, and the 1410cm -1 left and right - CH 3 and—CH 2 The appearance of new absorption peak...

Embodiment 2

[0031] Synthesis of stearic acid-modified hyaluronic acid. Take 5g of hyaluronic acid with a molecular weight of 50,000, and add 1g of stearic acid into a beaker, add 200mL of water, 100ml of dimethyl sulfoxide, and 1g of EDC and 0.5g of DMAP into the flask, stir magnetically, and react for 12 hours. After the reaction, put the product into a dialysis bag with a molecular weight of 8000-14000 for dialysis for 10 days, and freeze-dry to obtain stearic acid-modified hyaluronic acid.

Embodiment 3

[0033] Synthesis of stearic acid-modified hyaluronic acid. Take 1 g of hyaluronic acid with a molecular weight of 20,000 and 1 g of stearic acid into a beaker, add 10 mL of water, 10 mL of dimethyl sulfoxide, and 0.5 g of EDC and 0.2 g of DMAP into the flask, stir magnetically, and react for 6 hours. After the reaction, put the product into a dialysis bag with a molecular weight of 8,000-14,000 for dialysis for 5 days, and freeze-dry to obtain stearic acid-modified hyaluronic acid.

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Abstract

The invention relates to a modified hyaluronic acid based macromolecule lipidosome and a preparation method thereof. The grain size of the macromolecule lipidosome is 80-150 nm, and the Zeta potential is between minus 36 mV and minus 40 mV. The stearic acid modified hyaluronic acid is dissolved into dichloromethane to form an oil phase; the oil phase is subjected to ultrasonic operation at the power of 100-250 w, deionized water is added, then an ultrasonic generator is used for conducting ultrasonic dispersion to form a uniform emulsion disperse system; the emulsion is subjected to rotary evaporating on a rotary evaporator at the temperature of 25-50 DEG C and at the rotating speed of 20-100 r / min, and the macromolecule lipidosome is obtained after an organic solvent is completely volatilized. The grain size of the prepared macromolecule lipidosome is less than 150 nm and is uniform, and the dispersibility is good. The macromolecule lipidosome can freely move in blood so as to reduce the cytotoxic effect caused by positive electricity. The whole preparation process is simple and convenient, the preparation period is short, the yield is high, and the preparation method is applicable to batch production.

Description

technical field [0001] The invention relates to a polymer liposome based on modified hyaluronic acid and a preparation method thereof, belonging to the technical field of medicines. Background technique [0002] Liposomes are spherical particles with a diameter of tens of nanometers to several microns, which are formed by dispersing phospholipids in water. In 1965, Bangham et al. discovered liposomes, and liposomes were first used as drug carriers in the 1970s. Its bilayer structure can effectively wrap hydrophilic, lipophilic and macromolecular drugs, and can be used as a carrier for insoluble drugs to increase its local concentration; drugs are embedded in liposomes and released slowly, and liposomes in blood circulation The drug has a longer residence time than the free drug, thus prolonging the action time of the drug and having a long-term effect; the drug will improve the stability of the encapsulated drug due to liposome encapsulation, and it can also protect and dir...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/36A61K9/127C08B37/08
Inventor 常津宋昊王生
Owner TIANJIN UNIV
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