Method for preparing cyclodextrin metal organic framework (CD-MOF) stable in aqueous phase

Patent metadata

Field	Value
Publication number	US-11744903-B2
Application number	US-202318187709-A
Country	US
Kind code	B2
Filing date	Mar 22, 2023
Priority date	Mar 23, 2022
Publication date	Sep 5, 2023
Grant date	Sep 5, 2023

Abstract

A method for preparing a cyclodextrin metal organic framework (CD-MOF) stable in aqueous phase, including: dissolving β-cyclodextrin and solid potassium hydroxide in deionized water followed by magnetic stirring and ultrasonic treatment at room temperature, addition of methanol and stirring to obtain a reaction mixture; filtering the reaction mixture with a polytetrafluoroethylene membrane filter in a beaker; placing the beaker in methanol vapor to form a β-CD-MOF crystal; washing the β-CD-MOF crystal with ethanol followed by centrifugation and vacuum drying to obtain β-CD-MOF; preparing a β-CD-MOF-active substance complex by impregnation; and preparing an active substance-loaded β-CD-MOF-Tween 80 complex by physical adsorption modification followed by washing with anhydrous ethanol and vacuum drying.

First claim

What is claimed is:

1. A method for preparing a cyclodextrin metal organic framework (CD-MOF) stable in aqueous phase, comprising:
(1) dissolving 0.4254 g of β-cyclodextrin and 0.168 g of solid potassium hydroxide in 15 mL of deionized water followed by magnetic stirring at room temperature for 30 min, ultrasonic treatment at room temperature for 10-15 min, and addition of 9 mL of methanol to obtain a reaction mixture; and stirring the reaction mixture for 5 min for uniform mixing;
(2) filtering the reaction mixture with a polytetrafluoroethylene (PTFE) membrane filter to collect a filtrate in a first beaker;
(3) placing the first beaker in methanol vapor to form a β-cyclodextrin metal organic framework (β-CD-MOF) crystal;
(4) washing the β-CD-MOF crystal 2-3 times with 10-15 mL of ethanol followed by centrifugation at 5000 rpm for 10 min;
(5) subjecting the β-CD-MOF crystal to vacuum drying at 40-60° C. for 24 h to remove solvent in channels of the β-CD-MOF crystal to obtain β-CD-MOF;
(6) preparing an inclusion complex of an active substance and the β-CD-MOF by impregnation; wherein the active substance is selected from the group consisting of glycitein, naringenin, cinnamaldehyde, tanshinone IIA and resveratrol;
(7) preparing a crude active substance-loaded β-CD-MOF-Tween 80 complex stable in aqueous phase by physical adsorption modification;
wherein the physical adsorption modification is performed through steps of:
adding 0.2-0.6 mL of Tween 80 to a freshly-prepared anhydrous ethanol solution containing the inclusion complex followed by magnetic stirring at 80° C. for 30 min, cooling to room temperature and standing for 48 h to collect a precipitate as the crude active substance-loaded β-CD-MOF-Tween 80 complex;
(8) washing the crude active substance-loaded β-CD-MOF-Tween 80 complex 2-3 times with 10-15 mL of anhydrous ethanol followed by vacuum drying at 40-60° C. for 12 h to obtain a purified active substance-loaded β-CD-MOF-Tween 80 complex.

2. The method of claim 1 , wherein the PTFE membrane filter has a pore size of 0.45 μm.

3. The method of claim 1 , wherein step (3) comprises:
placing the first beaker in a second beaker containing 40-60 mL of methanol; wherein the second beaker is larger than the first beaker;
sealing the second beaker with a pressure-sensitive adhesive;
placing the second beaker in a magnetic field generator for 4 h; and
placing the second beaker in an electrothermal constant-temperature circulating water bath at 40-60° C. for 12 h to allow methanol to diffuse into the first beaker to obtain the β-CD-MOF crystal.

4. The method of claim 1 , wherein in step (6), the impregnation is performed through steps of:
ultrasonically dispersing 20 mg of the β-CD-MOF in 10 mL of anhydrous ethanol to obtain a β-CD-MOF solution; and adding a certain amount of the active substance to the β-CD-MOF solution, followed by stirring at 500 rpm for 1 h and standing for 12 h to obtain the inclusion complex.

Assignees

• Univ Qilu Technology

Inventors

• Yuan Chao
• Cui Bo
• Zhao Meng
• Lu Lu
• Li Jianpeng
• Liu Yaqi

Classifications

• A61K47/6951 Primary

  using cyclodextrin (cyclodextrins used as simple excipients A61K47/40) · CPC title

• A61K31/05 Primary

  Phenols {(cannabinoids A61K31/658)} · CPC title

• A61K31/11

  Aldehydes · CPC title

• A61K31/343

  condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone · CPC title

• A61K31/352

  condensed with carbocyclic rings, e.g. methantheline  {(cannabinoids A61K31/658)} · CPC title