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Preparation method of targeted graphene oxide binary medicine loading composite modified by HA/RGD

A composite material and graphene technology, which can be used in drug combinations, pharmaceutical formulations, medical preparations with non-active ingredients, etc., can solve the problems of curative effect and application promotion limitations, easy hydrolysis, and low water solubility of MEL, and improve the system. The effect of targeting, high release rate and mild experimental conditions

Inactive Publication Date: 2016-06-08
WUHAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, MEL has low water solubility and is easily hydrolyzed, which greatly limits its curative effect and application promotion.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] (1) Preparation of graphene oxide GO

[0028] Take 1.0g natural graphite powder, 0.5gNaNO 3 In a 250ml three-necked flask, slowly add 23ml of H 2 SO 4 . Then slowly add 3gKMnO 4 , keep the system temperature not exceeding 20°C, and keep stirring for 2h. The ice bath was removed, the system was heated to 35 °C, and stirring was continued for 2 h. Add 46ml of deionized water slowly, heat to 98°C, and stir for 30min. Then add 140ml deionized water and 10ml H 2 o 2 Stop the reaction. Filter while hot, wash thoroughly with 5% HCl and distilled water until the pH is close to neutral, filter with suction, and dry in vacuum at 60°C for 12h. The obtained solid powder was dispersed into deionized water (0.5mg / ml), ultrasonically exfoliated for 5h to obtain graphene oxide nanosheets, centrifuged for 30min (14000r / pm) to remove unexfoliated graphene oxide, and finally a brown GO suspension was obtained, which was freeze-dried Get GO powder.

[0029] (2) Amination of GO ...

Embodiment 2

[0038] (1) Preparation of graphene oxide GO

[0039] Take 1.0g natural graphite powder, 0.5gNaNO 3 In a 250ml three-necked flask, slowly add 23ml of H 2 SO 4 . Then slowly add 4gKMnO 4 , keep the system temperature not exceeding 20°C, and keep stirring for 2h. The ice bath was removed, the system was heated to 35 °C, and stirring was continued for 1.5 h. Add 46ml of deionized water slowly, heat to 98°C, and stir for 30min. Then add 140ml deionized water and 10ml H 2 o 2 Stop the reaction. Filter while hot, wash thoroughly with 5% HCl and distilled water until the pH is close to neutral, filter with suction, and dry in vacuum at 60°C for 12h. Disperse the obtained solid powder into deionized water (0.5ml / ml), ultrasonically exfoliate for 5h to obtain graphene oxide nanosheets, centrifuge for 30min (14000r / pm) to remove unexfoliated graphene oxide, and finally obtain a brown GO suspension, freeze-dry Get GO powder.

[0040] (2) Amination of GO

[0041] Dissolve 50 mg...

Embodiment 3

[0048] The preparation of embodiment 3MEL / DOX-GO-HA-RGD component

[0049] (1) Preparation of graphene oxide GO

[0050] Take 1.0g natural graphite powder, 0.5gNaNO 3 In a 250ml three-necked flask, slowly add 23ml of H 2 SO 4 . Then slowly add 5gKMnO 4 , keep the system temperature not exceeding 20°C, and keep stirring for 2h. The ice bath was removed, the system was heated to 35 °C, and stirring was continued for 1 h. Add 46ml of deionized water slowly, heat to 98°C, and stir for 30min. Then add 140ml deionized water and 10ml H 2 o 2 Stop the reaction. Filter while hot, wash thoroughly with 5% HCl and distilled water until the pH is close to neutral, filter with suction, and dry in vacuum at 60°C for 12h. Disperse the obtained solid powder into deionized water (0.5ml / ml), ultrasonically exfoliate for 5h to obtain graphene oxide nanosheets, centrifuge for 30min (14000r / pm) to remove unexfoliated graphene oxide, and finally obtain a brown GO suspension, freeze-dry Ge...

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PUM

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Abstract

The invention discloses a preparation method of a targeted graphene oxide binary medicine loading composite modified by HA / RGD. The method includes the following steps of conducting functional modification on graphene oxide through ADH to obtain aminated graphene oxide GO-ADH, coupling an METH connection bridge to HA through an amido bond in a covalent mode, conducting dialyzing and freeze-drying after stirring is conducted for 4-6 hours to obtain HA-METH, adding the obtained GO-ADH to obtain GO-HA-METH, adding sulfhydrylated RGD to obtain a GO-HA-RGD composite, dropwise adding a solution containing melphalan and a solution containing adriamycin, and conducting centrifuging, washing and freeze-drying to obtain MEL / DOX-GO-HA-RGD. The preparation method is easy to operate and mild in experimental condition. The whole carrier system is high in medicine loading amount, long-acting slow release can be achieved, pH sensitivity is achieved, the release rate under the low-pH-value environment is high, and the whole carrier system is suitable for micro environments of tumor tissue and has important clinical significance.

Description

technical field [0001] The invention belongs to the technical field of materials and biomedicine, and in particular relates to a method for preparing a HA / RGD modified targeted graphene oxide dual-loaded drug composite material. Background technique [0002] Graphene is a carbon nanomaterial with a two-dimensional planar structure, which has unique and excellent electrical, optical and mechanical properties. In recent years, the research applications of graphene derivatives in the field of biomedicine include biological components, microbial detection, disease diagnosis and drug delivery systems, etc. Its oxide graphene oxide has a large specific surface area, and the plane contains rich functions such as carboxyl, hydroxyl, and epoxy groups, which greatly improves its dispersibility, hydrophilicity, and compatibility with polymers. Chemical drugs, biomolecules, targeting groups, etc. can be effectively immobilized on graphene oxide through non-covalent or covalent bonds su...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K31/704A61P35/00C01B31/04B82Y30/00A61K31/196
CPCA61K31/196A61K31/704B82Y30/00C01P2004/34A61K2300/00
Inventor 许沛虎郭玉凤徐海星黄志军张凌溪李依萍周汇敏吴峰政杨夏雯
Owner WUHAN UNIV OF TECH
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