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Alpha-carboline chitosan derivative micelle as well as preparation method and application thereof

A technology of chitosan derivatives and carbolin, which is applied in the field of medicine, can solve the problems of hindering the effective treatment of myocardial ischemia-reperfusion injury diseases, obvious tolerance, and weak specificity, so as to improve water solubility and survival rate, reducing toxicity

Inactive Publication Date: 2019-03-22
GUIZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Drugs for the treatment of myocardial ischemia-reperfusion injury are well known in existing studies. Among the various known drugs, the more effective drugs are rosiglitazone, simvastatin, amiloride, and trimetazidine. However, these drugs still have defects such as weak specificity, low curative effect, and obvious tolerance to long-term use, which hinders the effective treatment of myocardial ischemia-reperfusion injury diseases
[0004] At present, α-carbolin derivatives have disadvantages in drug efficacy and application after hypoxia / reoxygenation injury of H9c2 cardiomyocytes outside the antibody: (1) low solubility, hydrophobicity, poor solubility in aqueous solution, and easy precipitation , need to add solubilizer, co-solvent or co-solvent to improve solubility; (2) has certain toxic and side effects, when H9c2 cardiomyocytes are administered in vitro (up to 800 μmol), the survival rate of H9c2 cells begins to decline; (3) in vitro anti- H9c2 cardiomyocytes have a certain drug effect after hypoxia / reoxygenation injury, but it is not ideal; therefore, improving the water solubility of α-carbolin derivatives and reducing their toxicity is the development and application of α-carbolin derivatives key issues

Method used

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  • Alpha-carboline chitosan derivative micelle as well as preparation method and application thereof
  • Alpha-carboline chitosan derivative micelle as well as preparation method and application thereof
  • Alpha-carboline chitosan derivative micelle as well as preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0038] A preparation method for α-carbolin chitosan derivative micelles, comprising the following steps:

[0039] (1) Synthesis of hydroxyethyl chitosan:

[0040] Weigh 1g of chitosan, put it into 5mL of 1% acetic acid solution to swell and dissolve, then add 15mL of 40% NaOH solution during the stirring process, use 40°C water bath to alkalinize for 16h, and then add 25mL of ethylene oxide dropwise under ice bath conditions , and stirred for 2 hours, heated up to 35°C, continued to react for 20 hours under condensing and reflux conditions, adjusted to neutrality with 1.5mol hydrochloric acid, transferred to a dialysis bag, dialyzed in double distilled water for 2 days, and freeze-dried to obtain hydroxyethyl chitosan.

[0041] (2) Synthesis of hydroxyethyl chitosan-octanoic acid conjugate:

[0042] a. Weigh 0.1g of hydroxyethyl chitosan, put it into 5mL distilled water for swelling, dissolve, and set aside;

[0043] b. Weigh 120 mg of N-hydroxysuccinimide and 70 mg of 1-(3-...

Embodiment 2

[0053] A preparation method for α-carbolin chitosan derivative micelles, comprising the following steps:

[0054] (1) Synthesis of hydroxyethyl chitosan:

[0055] Weigh 3g of chitosan, put it into 15mL of 3% acetic acid solution to swell and dissolve, then add 25mL of 60% NaOH solution during the stirring process, use a 50°C water bath to alkalinize for 24h, and then add 35mL of ethylene oxide dropwise under ice bath conditions , and stirred for 4 hours, heated to 45°C, continued to react for 26 hours under reflux conditions, adjusted to neutrality with 2.5mol hydrochloric acid, transferred to a dialysis bag, dialyzed in double distilled water for 4 days, and freeze-dried to obtain hydroxyethyl chitosan.

[0056] (2) Synthesis of hydroxyethyl chitosan-octanoic acid conjugate:

[0057] a. Weigh 0.5g of hydroxyethyl chitosan, put it into 15mL distilled water for swelling, dissolve, and set aside;

[0058] b. Weigh 150 mg of N-hydroxysuccinimide and 100 mg of 1-(3-dimethylamino...

Embodiment 3

[0068] A preparation method for α-carbolin chitosan derivative micelles, comprising the following steps:

[0069] (1) Synthesis of hydroxyethyl chitosan:

[0070] Weigh 2g of chitosan, put it into 10mL of 2% acetic acid solution to swell and dissolve, then add 20mL of 50% NaOH solution during the stirring process, use 45°C water bath to alkalinize for 18h, then add 30mL of ethylene oxide dropwise under ice bath conditions , and stirred for 3 hours, heated up to 40°C, continued to react for 24 hours under condensing and reflux conditions, adjusted to neutrality with 2mol hydrochloric acid, transferred to a dialysis bag, dialyzed in double distilled water for 3 days, and freeze-dried to obtain hydroxyethyl chitosan.

[0071] (2) Synthesis of hydroxyethyl chitosan-octanoic acid conjugate:

[0072] a. Weigh 0.2g of hydroxyethyl chitosan, put it into 10mL distilled water for swelling, dissolve, and set aside;

[0073] b. Weigh 130 mg of N-hydroxysuccinimide and 80 mg of 1-(3-dime...

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Abstract

The invention belongs to the technical field of medicine, in particular to alpha-carboline chitosan derivative micelle as well as a preparation method and application thereof. A hydroxyethyl chitosan-octanoic acid conjugate or hydroxyethyl chitosan-butyric acid is coupled into a carrier, a carboline derivative is encapsulated, according to the micelle, the particle sizes are less than 230 nm, thedrug loading capacity is about 16-23%, and the encapsulation efficiency is about 61-75%. The micelle provided by the invention has the characteristics of good water solubility, stable characters and low critical micelle concentration, and has broad application prospects in myocardial ischemia / reperfusion injury drugs.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to an α-carbolin-chitosan derivative micelle and a preparation method and application thereof. Background technique [0002] Ischemic heart disease (IHD) is the main cause of human death worldwide. Due to changes in the coronary circulation of the heart, myocardial damage caused by the imbalance between coronary blood flow and myocardial demand, the most The common cause is coronary artery stenosis and occlusion caused by coronary atherosclerosis, so it is also called coronary heart disease; clinically, it is manifested as angina pectoris, myocardial infarction, arrhythmia, severe and even comminuted death, and the disability and mortality rates are extremely high Therefore, the study of its pathogenesis and preventive treatment has always been a hot spot in medical research. When the blood flow is restored and the reperfusion is restored, the myocardial cell damage is aggravated,...

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K31/437A61K47/36A61P9/10
CPCA61K9/1075A61K31/437A61K47/36A61P9/10
Inventor 王磊廖尚高陈婷张金娟周孟何迅杨小生徐国波陈腾祥廖兴江关焕玉马良会熊英
Owner GUIZHOU MEDICAL UNIV