Betulinol derivative and hydrophilic modification product thereof, nano solution and preparation method of nano solution

The technology of a derivative, betulin, is applied in the field of betulin derivatives and their hydrophilic modified products, which can solve the problems of application limitations, difficulty in bioabsorption, and poor water solubility of betulin, and achieve improved antiviral activity and dispersibility Good, ideal particle size range

Active Publication Date: 2020-10-27
CHINA INSPECTION SCI PHARM BEIJING GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, due to the existence of pentacyclic triterpene structure in the molecule, the water solubility of betulin is generally poor, so it is difficult for organisms to absorb and affect its biological activity. Its application is limited

Method used

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  • Betulinol derivative and hydrophilic modification product thereof, nano solution and preparation method of nano solution
  • Betulinol derivative and hydrophilic modification product thereof, nano solution and preparation method of nano solution
  • Betulinol derivative and hydrophilic modification product thereof, nano solution and preparation method of nano solution

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0105] Example 2. Examples of hydrophilic modification of betulin derivatives

[0106] Esterification reaction: take a 500mL reaction flask, dissolve 2g of the crude product shown in formula 5, 4-dimethylaminopyridine (1.4g) and phthalic anhydride (3.35g) in 150mL of pyridine, and react at reflux at 120°C for 10 hours ,

[0107] The reaction formula is as follows:

[0108]

[0109]Recovery and purification: After the reaction, cool, add a large amount of water, extract three times with dichloromethane; wash three times with 10% hydrochloric acid, wash twice with saturated brine, dry over anhydrous sodium sulfate, and separate by column chromatography (dichloromethane:methanol=40:1 ), to obtain the compound shown in formula 8, according to the molar ratio of the product to the starting betulin, the yield is 85%.

[0110] Proton NMR spectrum (equipment Bruker 400MHz; solvent CDCl 3 ;Me 4 Si)0.76(3H,s),0.84(3H,s),0.85(3H,s),0.91(3H,s),0.95(3H,s),0.97(6H,s),3.20(1H),3.44 (...

Embodiment 3

[0111] Example 3 Examples of Hydrophilic Modified Products of Betulin Derivatives

[0112] Esterification reaction: take a 500mL reaction bottle, dissolve 2g of the crude product (4.52mmol) shown in Formula 5 in 200mL of dichloromethane, add 0.99g of pyromellitic dianhydride (4.52mmol) and 1.6mL of N,N-dichloromethane Isopropylethylamine was refluxed at 50°C for 8 hours.

[0113] The reaction formula is as follows:

[0114]

[0115] Recovery and purification: Add the reflux recovered product into 200mL of 1mol / L dilute hydrochloric acid, stir until a turbid precipitate appears, filter with suction, and wash with water. Dissolve the filter cake in 100 mL of acetic acid solution, heat to 100°C, and add 200 mL of water.

[0116] Cool, filter with suction, wash with 50% aqueous acetic acid, methanol, and dichloromethane, and dry to obtain compound 12. According to the molar ratio of the product to the starting betulin, the yield is 85%.

[0117] Proton NMR spectrum (equipmen...

Embodiment 4

[0118] Example 4. Preparation example of nano-solution of betulin and its derivatives' hydrophilic modification products

[0119] Nano-solution preparation steps: Accurately weigh the hydrophilic modified product, such as 20 mg of the compound shown in Formula 8, 60 mg of KOH, add to a round bottom flask, then accurately add 10 ml of pure water, heat and stir at 55 °C for 1 h, cool to After room temperature, transfer to a sealed bottle, add 2ml of Span, and ultrasonicate for 15 minutes to obtain a transparent and clear solution, which is tested by a laser nanometer particle size analyzer, such as figure 1 As shown, the particle size range is about 360nm, that is, the nano-solution of betulin derivatives (formula 8) is obtained, and its dispersibility is very good;

[0120] Control: the derivative shown in Formula 5 (without hydrophilization modification), after the nano solution preparation step, cannot form a transparent and clear nano solution, but generates a white precipit...

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Abstract

The invention relates to a betulin derivative and a hydrophilic modification product thereof, and a nano solution and a preparation method thereof, wherein the betulin derivative is a product obtainedby an esterification reaction of the 3-hydroxyl of betulin or the derivative thereof and the carboxyl in a benzoic acid derivative, the hydrophilic modification product is dispersed in water, a metalhydroxide salt is added, stirring is performed for 30-300 minutes at 25-90 DEG C, naturally cooling is performed to room temperature so as to make the compound form a carboxyl metal salt, a surfactant accounting for 0.1-10% of the volume of the reaction system is added, and ultrasonic treatment is performed for 0-60 min to obtain the nano colloid aqueous solution of the hydrophilic modification product of betulin and derivatives thereof, wherein the nano colloid aqueous solution is good in dispersity, ideal in particle size range and easy to absorb by organisms.

Description

technical field [0001] The invention relates to a chemical pharmaceutical method, in particular to a betulin derivative and its hydrophilic modification product, a nanometer solution and a preparation method. Background technique [0002] Betulin (such as formula 1), also known as betulin, betulin, betulin, is a rich and naturally occurring triterpene, widely found in birch, pomegranate bark and leaves, jujube seed, asparagus, etc. in plants. It has activities such as antiviral, anti-inflammatory, inhibiting the dissolution of proteins in hair fibers, promoting hair growth, and improving the luster of damaged hair. [0003] [0004] However, due to the existence of the pentacyclic triterpene structure in the molecule, betulin is generally poor in water solubility, so it is difficult for organisms to absorb it, which affects its biological activity, so its application is limited. Contents of the invention [0005] Based on the needs of the above-mentioned fields, the p...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J63/00C07J71/00A01N45/00A01N43/12A01P1/00
CPCC07J63/008C07J71/0005A01N45/00A01N43/12
Inventor 朱水芳田志清王晨光姜帆
Owner CHINA INSPECTION SCI PHARM BEIJING GRP CO LTD
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