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Preparation method of graphene drug carrier with folic acid and WGA (Wheat Germ Agglutinin) as targeting factors

A technology of graphene and folic acid, which is applied in the direction of drug combinations, pharmaceutical formulas, and medical preparations of non-active ingredients, etc., which can solve the problems of high rigidity of graphene, normal cell damage, and limited dispersion

Active Publication Date: 2018-08-14
QINGDAO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, graphene is too rigid and will cause a certain degree of damage to normal cells
In addition, graphene is highly hydrophobic and has limited dispersibility in aqueous solution.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0006] (1) Acyl chloride graphene oxide

[0007] Disperse 10.00g of graphene oxide (purity: 99%, thickness: ≤5nm, size: 2-8um) in 100mL of chloroform, raise the temperature to 55°C, slowly drop in 5.50g of thionyl chloride and 2.00g of N-formazan under stirring Base pyrrolidone, raise the temperature to boiling, reflux for 3 hours, cool down to 25°C, 3000 rpm, centrifuge for 10 minutes, pour off the supernatant, scrape off the precipitate, freeze-dry to obtain a brown solid powder, save it for later use;

[0008] (2) L-lysine grafted graphene oxide

[0009] Add 5.00gL-lysine to 50mL distilled water, stir and dissolve at 25°C, cool down to 10°C, and slowly add

[0010] The product of step (1) was stirred and reacted for 5 hours, then heated to 30°C, continued to stir and react for 2h, cooled to 25°C, filtered, washed with absolute ethanol for 3 times, and freeze-dried to obtain a white solid powder, which is used as wheat germ agglutinin for future use;

[0011] (3) Reduction...

Embodiment 2

[0018] (1) Particle size measurement

[0019] At 36.7°C, take 20mL of the sample of Example 1(5), 50w, 20Hz ultrasonic vibration for different times, drop it on the copper grid with supporting film, absorb the excess liquid on the filter paper, then drip the heavy metal complex dye, and absorb it on the filter paper The excess liquid was naturally dried for 45 minutes, and the particle size was measured with a scanning electron microscope. See Table 1.

[0020] Table 1 The average particle size of particles at rest for different times

[0021] Ultrasound time, min

5

10

15

20

25

30

Average particle size, um

0.17

0.23

0.25

0.28

0.27

0.27

[0022] (2) Zeta potential measurement

[0023] At 36.7°C, 20mL of the samples of Example 1(5) were taken, 50w, 20Hz ultrasonic vibration for different times, and the Zeta potentials of the particles in the solutions diluted in different times were measured. See Table 2.

[0024] Tab...

Embodiment 3

[0027] (1) Determination of particle size after binding with N-acetylneuraminic acid

[0028] At 36.7°C, take 20mL samples respectively, add them to the aqueous solution of 0.5% NaCl and 2% N-acetylneuraminic acid, take the samples that have been static for different times, drop them on the copper grid with the support film, absorb the excess liquid with filter paper, Drop the heavy metal complex dye again, absorb the excess liquid with filter paper, let it dry naturally for 45 minutes, and measure the particle size with a scanning electron microscope. See Table 3.

[0029] Table 3 The average particle size of the microparticles at different times after being combined with N-acetylneuraminic acid

[0030] standstill time, h

1

2

3

4

5

6

7

Average particle size, um

0.22

0.27

0.31

0.34

0.35

0.35

0.35

[0031] (2) Determination of Zeta potential after binding with N-acetylneuraminic acid

[0032] At 36.7°C, 20 mL of...

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Abstract

The invention relates to a graphene nano drug carrier with folic acid and wheat germ agglutinin as double targeting factors and prepared by adopting oxidized graphene, 6-carboxymethyl-gamma-cyclodextrin, the folic acid and wheat germ agglutinin (WGA) as main raw materials and a preparation method thereof. The preparation method comprises the following steps of: firstly adopting the oxidized graphene and paratoluensulfonyl chloride as raw materials, activating hydroxide radicals of the oxidized graphene, grafting L-lysine, and adopting hydrazine hydrate for reduction of the oxidized graphene grafted with the lysine; then reacting with the 6-carboxymethyl-gamma-cyclodextrin and the folic acid under the common catalysis of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) to generate nano graphene grafted with gamma-CD (Cyclodextrin) and the folic acid at the same time, then assembling the wheat germ agglutinin and the gamma-CD to prepare the graphene nano drug carrier with the folic acid and the wheat germ agglutinin as double targeting factors.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, in particular to a kind of folic acid and wheat germ agglutinin prepared from graphene oxide, 6-carboxymethyl-γ-cyclodextrin, folic acid and wheat germ agglutinin (WGA) as main raw materials Graphene nano drug carrier with dual targeting factors and its preparation method. Background technique [0002] In recent decades, various nanomaterials of different sizes, shapes and chemical compositions have been studied as nanocarriers for therapeutic drugs, including nanoparticles of metals and metal oxides, polymer micelles, liposomes, dendrimers substances and carbon nanotubes. Among them, graphene and graphene oxide, as a new and competitive drug delivery system due to their advantages in properties, have great application potential in systemic, targeted, and localized drug delivery systems. Graphene has a large specific surface area and a high drug loading capacity. Due to its special c...

Claims

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Application Information

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IPC IPC(8): A61K47/42A61K47/40A61K47/04A61K47/22A61P35/00C08G83/00
CPCA61K47/02A61K47/22A61K47/40A61K47/42A61P35/00C08G83/001
Inventor 麻金海方龙孔淑玲
Owner QINGDAO UNIV
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