CN106692975A - Oxidized-graphene nano-drug carrier with targeting function and preparing method thereof - Google Patents

Oxidized-graphene nano-drug carrier with targeting function and preparing method thereof Download PDF

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CN106692975A
CN106692975A CN201611087190.0A CN201611087190A CN106692975A CN 106692975 A CN106692975 A CN 106692975A CN 201611087190 A CN201611087190 A CN 201611087190A CN 106692975 A CN106692975 A CN 106692975A
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pyba
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graphene oxide
targeting
peg
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魏伟
潘祥华
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Changzhou Industrial Technology Research Institute of Zhejiang University
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Changzhou Industrial Technology Research Institute of Zhejiang University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones

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  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • General Chemical & Material Sciences (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention relates to an oxidized-graphene nano-drug carrier with a targeting function. The oxidized-graphene nano-drug carrier comprises oxidized-graphene, PyBA PEG FA and PyBA S S Drug. The invention further provides a preparing method of the oxidized-graphene nano-drug carrier, and the preparing method comprises the steps of firstly using polyethylene glycol with dual-amidogens be subjected to coupled reactions with folic acid and pyrene-1-butyric acid respectively to prepare PyBA PEG FA, conducting a reaction among pyrene-1-butyric acid and cystine and adriamycin amycin to prepare PyBA S S Drug, then mixing oxidized-graphene, PyBA PEG FA and PyBA S S Drug according to a certain proportion, conducting stirring and time treatment to some degree to obtain a nano-drug carrier solution with a certain concentration. The preparing method of the oxidized-graphene nano-drug carrier is simple in technology, and the obtained nano-drug carrier has high drug-carrying efficiency, and has a redox-responsive property and targeting property; meanwhile, various kinds of materials used for preparing the carrier have good biocompatibility.

Description

A kind of nano-medicament carrier based on graphene oxide and its system with targeting Preparation Method
Technical field
The present invention relates to field of medicaments, more particularly to a kind of nanometer medicine based on graphene oxide with targeting Thing carrier and preparation method thereof.
Background technology
With nanometer technology and growing, the research field of the nano-medicament carrier as hot topic of bio-pharmaceutical.Nanometer Pharmaceutical carrier can with high-efficient carrier medicine, targeted delivery medicine and controllably release medicine and can extend medicine act on when Ask there is that biocompatibility and toxic and side effect are small.Nano-medicament carrier can be divided into nanoparticle, nano liposomes, polymerization Thing glue card and nano magnetic particle.Common nano-medicament carrier has CNT, microballoon, liposome or ferrimagnetism particle Deng, they pass through adsorption, hydrogen bond, insertion or other reaction load medicines.
Graphene is a kind of novel nano-material with bi-dimensional cellular shape structure, and it has excellent mechanics, calorifics, electricity Learn and optical property.There is potential application at aspects such as biological medicine, biology sensor and electrochemistry.In recent years, some Person explores application of the Graphene in terms of biological medicine, particularly biological targeting and drug delivery aspect, achieves certain Achievement.Graphene has larger specific surface area, can be by its upper and lower surface and its edge load medicine, and load capacity is than it Its nano material is much higher.
The content of the invention
The first object of the present invention be solve in the prior art antineoplastic target drug delivery amount it is relatively low, toxic and side effect compared with Big defect, there is provided a kind of toxic and side effect is smaller, and circulation time is more long in blood, and with targeting and response medicine The nano-medicament carrier of release.
The present invention solve above-mentioned technical problem technical scheme be：It is a kind of with targeting based on graphene oxide Nano-medicament carrier, the nano-medicament carrier includes graphene oxide, PyBA-PEG-FA and PyBA-S-S-Drug；It is described Medicine in PyBA-S-S-Drug is one or more in adriamycin, Ce6 or protoporphyrin IX.
Preferably, the molecular weight of described polyethylene glycol is 1000~8000, at least the straight chain with two Amino End Groups or The polymer of many straight-arms.
The second object of the present invention be solve in the prior art antineoplastic target drug delivery amount it is relatively low, toxic and side effect compared with Big defect, there is provided a kind of toxic and side effect is smaller, and circulation time is more long in blood, and with targeting and response medicine The preparation method of the nano-medicament carrier of release.
The present invention solve above-mentioned technical problem technical scheme be：It is a kind of with targeting based on graphene oxide The preparation method of nano-medicament carrier, it is characterised in that comprise the following steps：
（1）Polyethylene glycol and 1- pyrenes butyric acid are added in organic solvent S1 according to certain ratio r1, in 50~100 DEG C of conditions Lower 2~12 hours a period of times of reaction, reaction is freeze-dried to obtain PyBA-PEG-NH after mixed liquor is dialysed after terminating2； Then by PyBA-PEG-NH2It is added in organic solvent S2 according to certain ratio r2 with folic acid, under the conditions of 50~100 DEG C 2~12 hours a period of times of reaction, reaction is freeze-dried to obtain PyBA-PEG-FA after mixed liquor is dialysed after terminating；
（2）Then Guang ammonia and 1- pyrenes butyric acid are added in organic solvent S3 according to certain ratio r3, one is reacted at normal temperatures 12~24 hours time of section, reaction is freeze-dried to obtain PyBA-S-S-NH after mixed liquor is dialysed after terminating2；Then will PyBA-S-S-NH2It is added to according to certain ratio r4 with antineoplastic after being processed into PyBA-S-S-COOH with succinic anhydride In organic solvent S4, at normal temperatures 12~24 hours a period of times of reaction, freeze-drying after mixed liquor is dialysed after terminating is reacted Can obtain PyBA-S-S-Drug；
（3）Then the graphene oxide solution of finite concentration C1 is peeled off into .5~1.5 hour with cell crushing instrument ultrasound；Then will PyBA-PEG-FA, PyBA-S-S-Drug and graphene oxide that abovementioned steps are obtained are scattered in organic according to certain ratio r5 S5 in solvent, then stirs 6~12 hours in lucifuge under normal temperature, is freeze-dried to obtain after then dialysing based on graphite oxide The nano-medicament carrier of alkene.
Preferably, the mol ratio r1 is 1:0.5~1:1.5, the organic solvent S1 are N ' dinethylformamides, four One or more in hydrogen furans, dioxane.
Preferably, the mol ratio r2 is 1:1~1:4, the organic solvent S2 are N ' dinethylformamides, tetrahydrochysene furan Mutter, one or more in dioxane, toluene, dichloromethane.
Preferably, the mol ratio r3 is 1:0.3~1:1, the organic solvent S3 are N ' dinethylformamides, tetrahydrochysene One or more in furans, dioxane, toluene, dichloromethane.
Preferably, the mol ratio r4 is 1:1~1:5, the organic solvent S4 are N ' dinethylformamides, tetrahydrochysene furan Mutter, one or more in dioxane, toluene, dichloromethane.
Preferably, described antineoplastic is adriamycin DOX, Ce6, protoporphyrin IX（protoporphyrin IX, PpIX）In one or more.
Preferably, the concentration C 1 is 0.5~2mg/mL.
Preferably, the mass ratio r5 is 10:0.5:10~10:3:20, the organic solvent S5 are N ' N- dimethyl One or two in formamide and tetrahydrofuran.
Brief description of the drawings
Fig. 1 is the structural representation of the folate-mediated nano-medicament carrier based on graphene oxide with reduction correspondence Figure.
Fig. 2 is the reaction preparation flow figure of PyBA-PEG-FA.
Fig. 3 is the reaction preparation flow figure of PyBA-S-S-DOX.
Fig. 4 is the dynamic light scattering grain-size graph of example 3.
Fig. 5 is the transmission electron microscope picture of example 3.
Specific embodiment
To enable the above objects, features and advantages of the present invention more obvious understandable, with reference to of the invention specific Implementation method is described in detail.Elaborate many details in order to fully understand the present invention in the following description.But It is that the present invention can be implemented with being much different from other manner described here, those skilled in the art can be without prejudice to originally Similar improvement is done in the case of invention intension, therefore the present invention is not limited by following public specific implementation.
It is below specific embodiment part.
Embodiment 1
By the polyethylene glycol NH that molecular weight is 30002-PEG-NH2With 1- pyrenes butyric acid according to mol ratio 1:0.5 be added to it is organic molten In agent DMF, the consumption of DMF is 30 times of reactant quality, is reacted under the conditions of 100 DEG C 6 hours, and reaction will be mixed after terminating PyBA-PEG-NH is freeze-dried to obtain after closing liquid dialysis2；Then by PyBA-PEG-NH2With folic acid according to mol ratio 1:2 add Enter in DMSO, 8 hours of a period of time are reacted under the conditions of 100 DEG C, react freeze-drying after mixed liquor is dialysed after terminating Can obtain PyBA-PEG-FA；
Then by Guang ammonia and 1- pyrenes butyric acid according to mol ratio 1:0.3 is added in organic solvent DMSO, and one section is reacted at normal temperatures 12 hours time, reaction is freeze-dried to obtain PyBA-S-S-NH after mixed liquor is dialysed after terminating2；Then by PyBA-S- S-NH2It is processed into after PyBA-S-S-COOH with antineoplastic DOX according to mol ratio 1 with succinic anhydride:4 be added to it is organic molten In agent dioxane, at normal temperatures 24 hours a period of times of reaction, freeze-drying after mixed liquor is dialysed after terminating is reacted Obtain PyBA-S-S-DOX；
Then the graphene oxide solution of 1mg/mL is used into cell crushing instrument ultrasound glass 1.0 hours under ice bath；Then will PyBA-PEG-FA, PyBA-S-S-DOX and graphene oxide are according to certain mass ratio 10:0.5:10 are scattered in DMSO, so Stirred 6 hours after lucifuge under normal temperature, the Nano medication based on graphene oxide is freeze-dried to obtain after then dialysing and is carried Body；
Weigh 5mg nano-medicament carriers to be dissolved in 5ml water, you can obtain folate-mediated having based on graphene oxide and reduce The nano-medicament carrier of correspondence.
Measured by Malvern Particle Size Analyzer, the average grain diameter of the pharmaceutical carrier is 130nm；
Calculated by ultraviolet spectra standard curve, the drugloading rate of the pharmaceutical carrier is 11.3%.
Embodiment 2
By the polyethylene glycol NH that molecular weight is 40002-PEG-NH2With 1- pyrenes butyric acid according to mol ratio 1:1 is added to organic solvent In DMSO, the consumption of DMSO is 10 times of reactant quality, is reacted under the conditions of 100 DEG C 8 hours, and reaction will be mixed after terminating PyBA-PEG-NH is freeze-dried to obtain after closing liquid dialysis2；Then by PyBA-PEG-NH2With folic acid according to mol ratio 1:3 add Enter in DMF, 12 hours of a period of time are reacted under the conditions of 100 DEG C, react freeze-drying after mixed liquor is dialysed after terminating Can obtain PyBA-PEG-FA；
Then by Guang ammonia and 1- pyrenes butyric acid according to mol ratio 1:0.6 is added in organic solvent DMSO, and one section is reacted at normal temperatures 18 hours time, reaction is freeze-dried to obtain PyBA-S-S-NH after mixed liquor is dialysed after terminating2；Then by PyBA-S- S-NH2It is processed into after PyBA-S-S-COOH with antineoplastic DOX according to mol ratio 1 with succinic anhydride:3 be added to it is organic molten In agent dioxane, at normal temperatures 12 hours a period of times of reaction, freeze-drying after mixed liquor is dialysed after terminating is reacted Obtain PyBA-S-S-DOX；
Then the graphene oxide solution of 1mg/mL is used into cell crushing instrument ultrasound glass 1.5 hours under ice bath；Then will PyBA-PEG-FA, PyBA-S-S-DOX and graphene oxide are according to certain ratio 10:1:15 are scattered in DMSO, Ran Houyu Lucifuge is stirred 12 hours under normal temperature, and be freeze-dried to obtain after then dialysing has reduction correspondence based on graphene oxide Nano-medicament carrier；
Weigh 5mg nano-medicament carriers to be dissolved in 5ml water, you can obtain a kind of folate-mediated having based on graphene oxide Nano-medicament carrier.
Measured by Malvern Particle Size Analyzer, the average grain diameter of the pharmaceutical carrier is 110nm；
Calculated by ultraviolet spectra standard curve, the drugloading rate of the pharmaceutical carrier is 13.8%.
Embodiment 3
By the polyethylene glycol NH2-PEG-NH that molecular weight is 50002With 1- pyrenes butyric acid according to mol ratio 1:0.5 be added to it is organic molten In agent DMF, reacted under the conditions of 80 DEG C 12 hours, reaction is freeze-dried to obtain after mixed liquor is dialysed after terminating PyBA-PEG-NH2；Then by PyBA-PEG-NH2With folic acid according to mol ratio 1:5 are added in DMF, anti-under the conditions of 100 DEG C Answer 6 hours, reaction is freeze-dried to obtain PyBA-PEG-FA after mixed liquor is dialysed after terminating；
Then by Guang ammonia and 1- pyrenes butyric acid according to mol ratio 1:1 is added in organic solvent DMSO, reacts 24 hours at normal temperatures, Reaction is freeze-dried to obtain PyBA-S-S-NH after mixed liquor is dialysed after terminating2；Then by PyBA-S-S-NH2With fourth two Acid anhydrides is processed into after PyBA-S-S-COOH with antineoplastic DOX according to mol ratio 1:5 are added to organic solvent dioxane In, to react 12 hours at normal temperatures, reaction is freeze-dried to obtain PyBA-S-S-DOX after mixed liquor is dialysed after terminating；
Then it is the graphene oxide solution of finite concentration 0.5mg/mL is small with cell crushing instrument ultrasound glass 1.0 under ice bath When；Then by PyBA-PEG-FA, PyBA-S-S-DOX and graphene oxide according to certain ratio 10:3:20 are scattered in DMSO In, then stirred 12 hours in lucifuge under normal temperature, be freeze-dried to obtain after then dialysing is had also based on graphene oxide The nano-medicament carrier of former correspondence；
Weigh 5mg nano-medicament carriers to be dissolved in 5ml water, you can obtain a kind of folate-mediated receiving based on graphene oxide Rice pharmaceutical carrier.
Measured by Malvern Particle Size Analyzer, the average grain diameter of the pharmaceutical carrier is 118nm (as shown in drawings)；
Calculated by ultraviolet spectra standard curve, the drugloading rate of the pharmaceutical carrier is 17.6%.
Embodiment 4
By the polyethylene glycol NH that molecular weight is 60002-PEG-NH2With 1- pyrenes butyric acid according to mol ratio 1:0.8 be added to it is organic molten In agent DMF, reacted under the conditions of 90 DEG C 12 hours, reaction is freeze-dried to obtain after mixed liquor is dialysed after terminating PyBA-PEG-NH2；Then by PyBA-S-S-NH2It is processed into after PyBA-S-S-COOH with folic acid according to mol ratio with succinic anhydride 1:3.5 are added in DMF, under the conditions of 80 DEG C react 12 hours, reaction terminate after mixed liquor is dialysed after freeze-drying i.e. Can obtain PyBA-PEG-FA；
Then by Guang ammonia and 1- pyrenes butyric acid according to mol ratio 1:0.5 is added in organic solvent DMSO, 24 is reacted at normal temperatures small When, reaction is freeze-dried to obtain PyBA-S-S-NH after mixed liquor is dialysed after terminating2；Then by PyBA-S-S-NH2With it is anti- Tumour medicine DOX is according to mol ratio 1:4 are added in organic solvent DMF, react 20 hours at normal temperatures, and reaction will be mixed after terminating PyBA-S-S-DOX is freeze-dried to obtain after closing liquid dialysis；
Then the graphene oxide solution of finite concentration 1mg/mL is used into cell crushing instrument ultrasound glass 0.5 hour under ice bath； Then by PyBA-PEG-FA, PyBA-S-S-DOX and graphene oxide according to certain ratio 10:3:20 are scattered in DMSO, Then stirred 8 hours in lucifuge under normal temperature, the Nano medication based on graphene oxide is freeze-dried to obtain after then dialysing Carrier；
5mg nano-medicament carriers are weighed to be dissolved in 5ml water.Can obtain a kind of folate-mediated is had based on graphene oxide Reduce the nano-medicament carrier of correspondence.
Measured by Malvern Particle Size Analyzer, the average grain diameter of the pharmaceutical carrier is 120nm；
Calculated by ultraviolet spectra standard curve, the drugloading rate of the pharmaceutical carrier is 12.8%.
Embodiment 5
By polyethylene glycol NH2-PEG-NH2 that molecular weight is 7000 with 1- pyrenes butyric acid according to mol ratio 1:0.5 be added to it is organic molten In agent DMF, reacted under the conditions of 100 DEG C 12 hours, reaction is freeze-dried to obtain after mixed liquor is dialysed after terminating PyBA-PEG-NH2；Then by PyBA-PEG-NH2 and folic acid according to mol ratio 1:5 are added in DMSO, under the conditions of 100 DEG C 8 hours of reaction, reaction is freeze-dried to obtain PyBA-PEG-FA after mixed liquor is dialysed after terminating；
Then by Guang ammonia and 1- pyrenes butyric acid according to mol ratio 1:1.5 are added in organic solvent DMSO, 12 are reacted at normal temperatures small When, reaction is freeze-dried to obtain PyBA-S-S-NH after mixed liquor is dialysed after terminating2；Then by PyBA-S-S-NH2Use fourth Dicarboxylic anhydride is processed into after PyBA-S-S-COOH with antineoplastic PpIX according to mol ratio 1:2 are added in organic solvent DMSO, React 6 hours at normal temperatures, reaction is freeze-dried to obtain PyBA-S-S-PpIX after mixed liquor is dialysed after terminating；
Then it is the graphene oxide solution of finite concentration 1.5mg/mL is small with cell crushing instrument ultrasound glass 1.0 under ice bath When；Then by PyBA-PEG-FA, PyBA-S-S-Drug and graphene oxide according to certain ratio 10:0.5:16 are scattered in In DMSO, then stirred 6 hours in lucifuge under normal temperature, be freeze-dried to obtain after then dialysing is had based on graphene oxide Reduce the nano-medicament carrier of correspondence；
5mg nano-medicament carriers are weighed to be dissolved in 5ml water.Can obtain a kind of folate-mediated is had based on graphene oxide Reduce the nano-medicament carrier of correspondence.
Measured by Malvern Particle Size Analyzer, the average grain diameter of the pharmaceutical carrier is 90nm；
Calculated by ultraviolet spectra standard curve, the drugloading rate of the pharmaceutical carrier is 8.9%.
Embodiment 6
By the polyethylene glycol NH that molecular weight is 80002-PEG-NH2With 1- pyrenes butyric acid according to mol ratio 1:0.5 be added to it is organic molten In agent DMF, reacted under the conditions of 60 DEG C 6 hours, reaction is freeze-dried to obtain after mixed liquor is dialysed after terminating PyBA-PEG-NH2；Then by PyBA-PEG-NH2With folic acid according to mol ratio 1:2 are added in DMSO, anti-under the conditions of 100 DEG C Answer 12 hours, reaction is freeze-dried to obtain PyBA-PEG-FA after mixed liquor is dialysed after terminating；
Then by Guang ammonia and 1- pyrenes butyric acid according to mol ratio 1:1.5 are added in organic solvent DMSO, 12 are reacted at normal temperatures small When, reaction is freeze-dried to obtain PyBA-S-S-NH after mixed liquor is dialysed after terminating2；Then by PyBA-S-S-NH2Use fourth Dicarboxylic anhydride is processed into after PyBA-S-S-COOH with antineoplastic Ce6 according to mol ratio 1:1 is added in organic solvent DMSO, React 24 hours at normal temperatures, reaction is freeze-dried to obtain PyBA-S-S-Ce6 after mixed liquor is dialysed after terminating；
Then the graphene oxide solution of finite concentration 2mg/mL is used into cell crushing instrument ultrasound glass 1.0 hours under ice bath； Then by PyBA-PEG-FA, PyBA-S-S-Drug and graphene oxide according to certain ratio 10:3:15 are scattered in DMSO, Then stirred 12 hours in lucifuge under normal temperature, be freeze-dried to obtain after then dialysing has reduction phase based on graphene oxide The nano-medicament carrier of answering property；
5mg nano-medicament carriers are weighed to be dissolved in 5ml water.Can obtain a kind of folate-mediated receiving based on graphene oxide Rice pharmaceutical carrier.
Measured by Malvern Particle Size Analyzer, the average grain diameter of the pharmaceutical carrier is 100nm；
Calculated by ultraviolet spectra standard curve, the drugloading rate of the pharmaceutical carrier is 11.9%.

Claims (10)

1. a kind of nano-medicament carrier based on graphene oxide with targeting, it is characterised in that the Nano medication is carried Body includes graphene oxide, PyBA-PEG-FA and PyBA-S-S-Drug；Medicine in the PyBA-S-S-Drug is Ah mould One or more in element, Ce6 or protoporphyrin IX.
2. there is the nano-medicament carrier based on graphene oxide of targeting as claimed in claim 1, it is characterised in that The molecular weight of the described polyethylene glycol is 1000~8000, at least with two polymerizations of the straight chain or many straight-arms of Amino End Group Thing.
3. there is the preparation side of the nano-medicament carrier based on graphene oxide of targeting as claimed in claim 1 or 2 Method, it is characterised in that comprise the following steps：
（1）Polyethylene glycol and 1- pyrenes butyric acid are added in organic solvent S1 according to certain ratio r1, in 50~100 DEG C of conditions Lower reaction 2~12 hours, reaction is freeze-dried to obtain PyBA-PEG-NH after mixed liquor is dialysed after terminating2；Then will PyBA-PEG-NH2Be added in organic solvent S2 according to certain ratio r2 with folic acid, under the conditions of 50~100 DEG C react 2~ 12 hours, reaction was freeze-dried to obtain PyBA-PEG-FA after mixed liquor is dialysed after terminating；
（2）Then Guang ammonia and 1- pyrenes butyric acid are added in organic solvent S3 according to certain ratio r3,12 is reacted at normal temperatures ~24 hours, reaction was freeze-dried to obtain PyBA-S-S-NH after mixed liquor is dialysed after terminating2；Then by PyBA-S-S- NH2After being processed into PyBA-S-S-COOH with succinic anhydride organic solvent is added to antineoplastic according to certain ratio r4 In S4, react 12~24 hours at normal temperatures, reaction is freeze-dried to obtain PyBA-S-S- after mixed liquor is dialysed after terminating Drug；
（3）Then the graphene oxide solution of finite concentration C1 is peeled off 0.5~1.5 hour with cell crushing instrument ultrasound；Then PyBA-PEG-FA, PyBA-S-S-Drug and graphene oxide that abovementioned steps are obtained are scattered according to certain ratio r5 and have S5 in machine solvent, then stirs 6~12 hours in lucifuge under normal temperature, is freeze-dried to obtain after then dialysing based on oxidation stone The nano-medicament carrier of black alkene.
4. there is the preparation method of the nano-medicament carrier based on graphene oxide of targeting as claimed in claim 3, It is characterized in that the mol ratio r1 is 1:0.5~1:1.5, the organic solvent S1 are N ' dinethylformamides, tetrahydrochysene furan Mutter, one or more in dioxane.
5. there is the preparation method of the nano-medicament carrier based on graphene oxide of targeting as claimed in claim 3, It is characterized in that the mol ratio r2 is 1:1~1:4, the organic solvent S2 are N ' dinethylformamides, tetrahydrofuran, two One or more in the ring of oxygen six, toluene, dichloromethane.
6. there is the preparation method of the nano-medicament carrier based on graphene oxide of targeting as claimed in claim 3, It is characterized in that the mol ratio r3 is 1:0.3~1:1, the organic solvent S3 be N ' dinethylformamides, tetrahydrofuran, One or more in dioxane, toluene, dichloromethane.
7. there is the preparation method of the nano-medicament carrier based on graphene oxide of targeting as claimed in claim 3, It is characterized in that the mol ratio r4 is 1:1~1:5, the organic solvent S4 are N ' dinethylformamides, tetrahydrofuran, two One or more in the ring of oxygen six, toluene, dichloromethane.
8. there is the preparation method of the nano-medicament carrier based on graphene oxide of targeting as claimed in claim 3, It is characterized in that described antineoplastic is one or more in adriamycin DOX, Ce6, protoporphyrin IX.
9. there is the preparation method of the nano-medicament carrier based on graphene oxide of targeting as claimed in claim 3, It is characterized in that the concentration C 1 is 0.5~2mg/mL.
10. there is the preparation method of the nano-medicament carrier based on graphene oxide of targeting as claimed in claim 3, It is characterized in that the mass ratio r5 is 10:0.5:10~10:3:20, the organic solvent S5 is N ' dinethylformamides With one or two in tetrahydrofuran.
CN201611087190.0A 2016-12-01 2016-12-01 Oxidized-graphene nano-drug carrier with targeting function and preparing method thereof Pending CN106692975A (en)

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CN107375214A (en) * 2017-07-27 2017-11-24 重庆医科大学 A kind of modified with folic acid montmorillonite nano preparation for carrying medicine and preparation method thereof
CN107982542A (en) * 2017-11-09 2018-05-04 大连理工大学 A kind of preparation method of new polyethyleneglycol modified nano graphene oxide delivery system
CN108314015A (en) * 2018-03-16 2018-07-24 江南大学 A kind of preparation method of functionalization graphene aerogel microball
CN109568596A (en) * 2017-09-28 2019-04-05 中国科学院深圳先进技术研究院 Placenta sample chondroitin sulfate A (CSA) targets carrier systems and its preparation method and application

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Application publication date: 20170524