Heparin or heparin salt modified graphene oxide and preparation method and application thereof

A technology of graphene and stone oxide, applied in the field of graphene oxide modified by heparin or its salt and its preparation

Active Publication Date: 2016-02-24
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no relevant report on the combination of graphene oxide and heparin or its salt, and its application in drug carrier materials.

Method used

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  • Heparin or heparin salt modified graphene oxide and preparation method and application thereof
  • Heparin or heparin salt modified graphene oxide and preparation method and application thereof
  • Heparin or heparin salt modified graphene oxide and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0123] Graphene oxide-heparin conjugate

[0124] ⑴Preparation of Graphene Oxide (GO) Take 0.40kg of graphite powder, slowly add 2.40 liters of concentrated sulfuric acid, 0.60kg of potassium persulfate and 0.60kg of phosphorus pentoxide, heat to 80°C, stir for 10-24h to obtain a dark blue mixture , gradually cooled to room temperature, added 10 liters of purified water, filtered, collected residue, and dried overnight at 60°C to obtain pre-oxidized graphite powder. Get preoxidized graphite powder 0.20kg, slowly add 15 liters (0 ℃) in the concentrated sulfuric acid of ice bath, under ice bath condition, slowly add potassium permanganate 2.5kg while stirring. Stirring was continued for half an hour after the addition was complete, and then the temperature of the reaction solution was gradually raised to 40° C. and stirred for 8 hours. Slowly add a mixture of 75 liters of purified water and 3 liters of hydrogen peroxide (30 wt%) to terminate the above reaction. Stand overnight,...

Embodiment 2

[0128] Reduced graphene oxide-heparin conjugate

[0129] (1) Preparation of reduced graphene oxide (rGO) Take 1 liter of GO colloidal solution in the above-mentioned embodiment 1 (1), make 0.1g / L aqueous solution, add 2g of vitamin C, ultrasonic 30min at 60°C, then add 5g of sodium chloride, let stand 2h, centrifuge at 4000rpm for 1000min, collect the precipitate, wash twice with ethanol and pure water respectively, centrifuge at 4000rpm for 1000min, reduce graphene oxide, suspend with purified water, and sonicate for 1h to obtain a colloidal solution of rGO.

[0130] (2) Preparation of rGO modified by ADH-UFH (rGO-ADH-UFH) Take 1 liter of 1 mg / mL rGO solution, add 28.7 g of EDC·HCl and 32.5 g of sulfur-NHS, adjust the pH value of the solution to 6.4, and stir at 25-30°C for 1.5 h, to activate the carboxylic acid group. Add 10 g of ADH-UFH in the above-mentioned Example 1 (2), stir and react at 25-30° C. for 20 h, dialyze to remove unreacted starting materials, and obtain rGO...

Embodiment 3

[0132] Graphene oxide-low molecular weight heparin conjugate

[0133] ⑴Preparation of low molecular weight heparin modified by adipate dihydrazide (ADH-LMWH) Dissolve 10g of low molecular weight heparin sodium in 1 liter of water, add 2g of ADH, 8g of EDC·HCl and 6g of HOBt, and adjust the pH value of the solution to 6.6. 25~ The reaction was stirred at 30°C for 36h. The unreacted substances were removed by dialysis with water and freeze-dried to obtain the product. Figure 7 It is a typical infrared spectrum of adipate dihydrazide modified low molecular weight heparin.

[0134] (2) Preparation of ADH-UFH-modified GO (GO-ADH-LMWH) Take 1 liter of 1 mg / mL graphene oxide solution in Example 1 (1) above, add EDC·HCl 26g and sulfur-NHS 30g, adjust the pH value of the solution to 6.2, 25-30°C The reaction was stirred for 2h to activate the carboxylic acid group. 10 g of ADH-LMWH was added, stirred and reacted at 25-30°C for 18 hours, and unreacted starting materials were removed...

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Abstract

The present invention discloses heparin or heparin salt modified graphene oxide and a preparation method and application thereof, the modified graphene oxide can be used as a drug, particularly an anti-cancer drug carrier material. By use of pH sensitive principle, adipic dihydrazide is used as a linker molecule, or by use of redox principle, cystamine is used as a linker molecule, heparin is used for chemically modifying graphene oxide, and the heparin has the advantages of increase of water solubility and anti-cancer drug tumor synergistic effect of graphene oxide, and solves the problems of poor water solubility and easy aggregation and the like of the graphene oxide.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a graphene oxide used for heparin or its salt modification and its preparation method and application. Background technique [0002] Graphene oxide (Grapheneoxide, GO, see figure 1 ) is a derivative of graphene with a monoatomic layer structure (Carbon, 2011, 49:1126-1132). Compared with graphene (Graphene) which only contains carbon-carbon double bonds on the surface, graphene oxide itself contains a large number of oxygen-containing groups such as hydroxyl, epoxy, and carboxyl groups, and has better hydrophilicity. Widely used in biomedicine (JControlRelease, 2014, 173:75-88). Since graphene oxide has a single atomic layer structure, it has a large specific surface area (736.6m2 measured in literature). 2 / g, see Langmuir, 2013, 29:13443-13448), both sides of which can be combined with drugs through covalent and non-covalent interactions, so they have a higher drug load. It ca...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K47/04A61K31/727A61K45/06A61P35/00
Inventor 翟光喜汪洋
Owner SHANDONG UNIV
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