A kind of preparation method of puerarin hyaluronic acid nano-micelle

A technology of hyaluronic acid and nano-micelle, which is applied to medical preparations with non-active ingredients, medical preparations containing active ingredients, and pharmaceutical formulas, etc. It can solve the problems of poor fat solubility and water solubility, and achieve high drug loading , The preparation technology is simple and stable, and the effect of convenient operation

Inactive Publication Date: 2021-01-05
QINGDAO UNIV OF SCI & TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Aiming at the technical problem that the puerarin molecular structure in the prior art has soybean isoflavone structure, so its fat solubility and water solubility are relatively poor, and its application is greatly restricted, the purpose of the present invention is to provide a Preparation method of puerarin hyaluronic acid nano-micelle

Method used

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  • A kind of preparation method of puerarin hyaluronic acid nano-micelle
  • A kind of preparation method of puerarin hyaluronic acid nano-micelle
  • A kind of preparation method of puerarin hyaluronic acid nano-micelle

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Embodiment 1

[0033] First add hyaluronic acid into deionized water to fully dissolve, and then make a solution with a mass concentration of 0.4%, and add catalysts DCC and HOBt to it to prepare solution I. Then adipic acid dihydrazide (ADH) was added into deionized water to dissolve to obtain solution II with a mass concentration of 1%. Add solution I dropwise to solution II under stirring condition, by adding pH adjusting reagent-hydrochloric acid to adjust the pH of the system to pH4, controlling the reaction temperature at 5°C, stirring speed at 1000rpm and reaction time of 24 hours, the hyaluronic acid-ADH intermediate is obtained and the mixed solution of the catalyst, and then separate and dry it to obtain the hyaluronic acid-ADH intermediate of the present invention; under stirring conditions, an appropriate amount of hyaluronic acid-ADH intermediate and puerarin are fully dissolved, and then the catalyst EDC is added thereto And solutions such as DMAP, by adding pH adjustment reage...

Embodiment 2

[0035]Partially deacetylated hyaluronic acid was added into deionized water to fully dissolve it, and then a solution with a mass concentration of 1% was prepared, and catalysts EDC and NHS were added to it to obtain solution I. Then adipic acid dihydrazide (ADH) was added into deionized water to dissolve to obtain solution II with a mass concentration of 8%. Add solution I dropwise to solution II under stirring conditions, adjust the pH of the system to pH 10 by adding a pH adjusting reagent-ammonium bicarbonate, control the reaction temperature at 25°C, the stirring speed at 5000rpm and the reaction time for 12 hours to obtain partially deacetylated transparent The mixed solution of hyaluronic acid-ADH intermediate and catalyst is then separated and dried to obtain the hyaluronic acid-ADH intermediate of the present invention; under stirring conditions, an appropriate amount of deacetylated hyaluronic acid-ADH intermediate and amber Ester puerarin is fully dissolved, and the...

Embodiment 3

[0037] First add methyl hyaluronate into deionized water to fully dissolve, then prepare a solution with a mass concentration of 1.2%, and add catalysts PyBop and DIEA to it to prepare solution I. Then adipic acid dihydrazide (ADH) was added into deionized water to dissolve to obtain a solution II with a mass concentration of 10%. Add solution I dropwise to solution II under stirring conditions, adjust the pH of the system to pH 12 by adding a pH adjustment reagent-sodium hydroxide, control the reaction temperature at 60°C, the stirring speed at 10,000 rpm and the reaction time for 1 hour to obtain methyl hyaluronate - the mixed solution of ADH intermediate and catalyst, then it is separated and dried to obtain methyl hyaluronate-ADH intermediate of the present invention; under stirring conditions, an appropriate amount of methyl hyaluronate-ADH intermediate and succinic acid Fully dissolve the ester puerarin, then add catalysts such as DIC and DMAP to it, adjust the pH of the...

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Abstract

The invention discloses a preparation method of puerarin and hyaluronic acid nano-micelles. The method comprises the following steps that 1, a solution I of a hyaluronic acid derivative is obtained through dissolution; 2, ADH is dissolved to prepare a solution II; 3, the solution I is added into the solution II drop by drop, the system pH is adjusted, and after reaction, a hyaluronic acid-ADH intermediate is obtained through centrifugal separation and drying; 4, the hyaluronic acid-ADH intermediate and a puerarin derivative are fully dissolved, and then a catalyst is added into the mixture toprepare the puerarin and hyaluronic acid nano-micelles; 5, the puerarin and hyaluronic acid nano-micelles are added into an organic dispersion phase, the puerarin and hyaluronic acid nano-micelles andpuerarin are mixed, dialysis treatment is conducted, and finally, a solid product of the puerarin and hyaluronic acid nano-micelles is obtained. The method has the advantages that operation is convenient, the preparation technology is simple and stable, and the production cost is low; by means of the study, the curative effect of the puerarin is improved, adverse reaction of the puerarin is reduced, and a novel production technology is provided for developing a novel puerarin replacement medicine.

Description

technical field [0001] The invention belongs to the technical field of new drug research and development, and in particular relates to a preparation method of puerarin-hyaluronic acid nano-micelle. Background technique [0002] Puerarin is a flavonoid glycoside extracted from Pueraria mirifica, the chemical name is 8-β-D-glucopyranose-4', 7-dihydroxyisoflavone. Studies have shown that puerarin has a significant expansion Coronary artery and cerebrovascular, reduce catecholamine level, β-receptor blocking effect, can protect myocardial cells, effectively reduce myocardial oxygen consumption, widely used clinically in the treatment of cardiovascular and cerebrovascular diseases, peripheral vascular diseases, diabetes and other diseases. Due to the soybean isoflavone structure in the molecular structure of puerarin, its fat solubility and water solubility are poor, which hinders the better curative effect of puerarin in clinical treatment and greatly restricts its application. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/61A61K47/69A61K9/107A61K31/352A61P9/10A61P3/10
CPCA61K9/1075A61K31/352A61K47/61A61K47/6907A61P3/10A61P9/10
Inventor 宋益民李媛媛高杨周莉满华罗尚潘爱红邢明霞
Owner QINGDAO UNIV OF SCI & TECH
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