CN105310998A - Microcapsule containing functionalized graphene in capsule wall and preparation method of microcapsule - Google Patents
Microcapsule containing functionalized graphene in capsule wall and preparation method of microcapsule Download PDFInfo
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- CN105310998A CN105310998A CN201510736120.2A CN201510736120A CN105310998A CN 105310998 A CN105310998 A CN 105310998A CN 201510736120 A CN201510736120 A CN 201510736120A CN 105310998 A CN105310998 A CN 105310998A
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Abstract
The invention relates to a microcapsule containing functionalized graphene in a capsule wall and a preparation method of the microcapsule. In the microcapsule, a crosslinked membrane of sulfhydrylized graphene obtained by modifying a compound which simultaneously contains sulfhydryl and amino or bio-molecules is used as the capsule wall, and an oil phase which is loaded with hydrophobic drugs is used as a core material. The preparation method is achieved by ultrasonically radiating a water solution containing the sulfhydrylized graphene and the oil phase which is loaded with the hydrophobic drugs so as to obtain the microcapsule which contains the functionalized graphene in the capsule wall. The microcapsule disclosed by the invention is capable of achieving the controlled release of the drugs on the basis of the reducing responsiveness of a disulfide bond; and the preparation method is simple to operate, efficient and rapid and high in drug loading capacity, and the preparation method is not easy to introduce impurities, widely applicable to the cladding of the hydrophobic drugs and excellent in application prospect.
Description
Technical field
The present invention relates to a kind of bio-medical material, especially cyst wall contains microcapsule and the preparation method of functionalization graphene.
Background technology
Microcapsule is a kind of miniature vessel or packing material with particular geometric configuration, due to the particularity of its structure and the polytropy of performance, is all widely used in fields such as agricultural, food and biological medicines.The material preparing microcapsule is varied, mainly comprises the macromolecular material and inorganic compound etc. of natural macromolecular material, synthesis.The method preparing microcapsule has a lot, according to encystation mechanism, can be roughly divided into three classes: Physical, physical-chemical process and chemical method.In recent years, there is the technology of some new micro encapsulation, as surface grafting, matrix polymerization, LBL self-assembly etc.These technology are all the Microencapsulation Method based on chemical reaction, have structure-controllable, performance is adjustable, be easy to give the features such as various feature functionalitys.But more loaded down with trivial details, the consuming time length of these method operating process, and be easy to introduce impurity etc., which has limited their practical application.
The method that microcapsule is prepared in ultrasonic radiation is invented in the early 1990s by people such as the scientist Suslick of the U.S., and they utilize the ultrasonic radiation of high strength gas or water-fast liquid protein to be included, and are prepared into protein microcapsules.This method is simple to operate, and efficient quick is environmental protection again, and the microcapsule obtained has good biocompatibility, has potential using value in fields such as drug techniques.
Graphene oxide has larger specific surface area, good biocompatibility, is a kind of good pharmaceutical carrier.Nano graphene oxide after polyethyleneglycol modified is used as the carrier of water-soluble anti-tumor medicine by the people such as Xu.The people such as Bao modify graphene oxide with chitosan, load p-DNA and antitumor drug hydroxycamptothecin, and work out this drug-supplying system and p-DNA can be transported to inside tumor cells, and have obvious slow releasing function to hydroxycamptothecin.But yet there are no the report utilizing ultrasonic method to prepare functionalization graphene microcapsule.
Summary of the invention:
An object of the present invention is for above-mentioned the deficiencies in the prior art, there are provided the microcapsule that a kind of cyst wall contains functionalization graphene;
Another object of the present invention is to provide the preparation method that a kind of cyst wall contains the microcapsule of functionalization graphene.
The object of the invention is to be achieved through the following technical solutions:
Principle of the present invention: be with the catalytic action of high-strength ultrasonic at oil/water interface, the sulfydryl of sulfhydrylation graphenic surface is impelled to occur crosslinked, form stable cross linking membrane, and by coated for the oil phase being loaded with hydrophobic drug, formed with the cross linking membrane of sulfhydrylation Graphene for cyst wall, the oil phase being mounted with hydrophobic drug is the drug-loading microcapsule of core.
A kind of cyst wall contains the microcapsule of functionalization graphene, by carrying out ultrasonic radiation to the aqueous solution simultaneously containing the sulfhydrylation Graphene obtained after sulfydryl and amino compound or biomolecule modification with the oil phase being mounted with hydrophobic drug, formed with the cross linking membrane of sulfhydrylation Graphene as cyst wall, to be loaded with the drug-loading microcapsule of oil phase for core of hydrophobic drug, the size of microcapsule is between 0.2-30 μm.
Containing sulfydryl and amino compound or biomolecule while described is that 4-amino-3-hydrazine-5-dredges base-1,2,4-triazole, 2-sulfydryl-4-amino-6-hydroxy pyrimidine, 6-sulfydryl-2,4-di-amino-pyrimidine, 1-amino-5-sulfydryl anthraquinone, 2-amino-6-hydroxyl-8-purinethol, 2-amino-Ismipur, 3-amino-5-sulfydryl-1,2,4-triazole, 2-amino-5-mercaptobenzoic acid, 2-sulfydryl-4-amino-7H-pyrroles [2,3-d] pyrimidine, 3-amino-4-mercaptoquinoline, 4-amino-3-sulfydryl-4H-1,2,4-triazole, 2-amino-6-sulfydryl-3H-pyrimidin-4-one, amino-Polyethylene Glycol-sulfydryl, 5-amino-2-mercapto phenyl formic-4-thiazole carboxamides, 2-amino-3-sulfydryl-3-methyl fourth carboxylic acid, 2-amino-3-sulfydryl-1-propanol, 2-amino-5-sulfydryl-1,3,4-thiadiazoles, 5-amino-2-mercapto phenyl formic thiazole, sulfydryl undecylamine and hydrochlorate thereof, 5-amino-1-mercaptopentane and hydrochlorate thereof, 6-amino-1-mercapto hexane and hydrochlorate thereof, cysteamine and hydrochlorate thereof, cysteine and hydrochlorate thereof, homocysteine or glutathion.
Described hydrophobic drug is one or more in paclitaxel, lomustine, ginsenoside, camptothecine or silymarin medicine.
Described oil phase is the immiscible nontoxic liquid state organics of the various animal oil of biological medicine, vegetable oil, microbial grease, mineral oil, silicone oil or other and water.
Cyst wall contains a preparation method for the microcapsule of functionalization graphene, comprises the following steps:
A, by 5-20mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the DIC of 20-150mg, dicyclohexylcarbodiimide or the aqueous solution containing 20-150mg1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride;
B, at N
2under protection, while adding 10-50mg, contain compound or the biomolecule of sulfydryl and amino;
Stirring reaction 2-24 hour under c, oxygen free condition, 3-5 centrifuge washing, removes unreacted simultaneously containing sulfydryl and amino compound or biomolecule, obtains sulfhydrylation Graphene;
D, the sulfhydrylation graphene uniform of preparation is scattered in deionized water, measures the aqueous solution of sulfhydrylation Graphene and the oil phase containing hydrophobic drug with test tube by certain volume ratio, be placed in ice-water bath;
E, ultrasonic probe is placed in oil/water two-phase interface, under certain ultrasonic power, acts on a period of time;
F, centrifuge washing is carried out to reactant liquor, obtain with the cross linking membrane of sulfhydrylation Graphene for cyst wall, the drug-loading microcapsule being core with the oil phase of hydrophobic drug.
6, contain the microcapsule of functionalization graphene according to a kind of cyst wall according to claim 5, it is characterized in that, the volume ratio of the described aqueous solution containing sulfhydrylation Graphene and the oil phase containing hydrophobic drug is 1:1-20:1.
7, contain the microcapsule of functionalization graphene according to a kind of cyst wall according to claim 5, it is characterized in that, described ultrasonic power is 20-1000W/cm
2, ultrasonic time is 0.5-20min.
Beneficial effect: functionalization graphene can be evenly distributed on the cyst wall of microcapsule by the present invention, reduces Graphene to greatest extent and is loaded into the contact of capsule-core Chinese medicine, thus reduces its impact on drug effect; The Graphene cyst wall formed plays bag to medicine and carries and protective effect; Utilize the reduction response of disulfide bond effectively can control the release of medicine; Preparation method of the present invention is fast and convenient, high-efficiency environment friendly, and material source is extensive, and products pure is nontoxic.
Detailed description of the invention:
Below in conjunction with embodiment, the present invention is described in further detail:
Embodiment 1
By 5mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the aqueous solution containing 20mg1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride; At N
2under protection, the 4-amino-3-hydrazine-5-adding 10mg dredges base-1,2,4-triazole, stirring reaction 2 hours under oxygen free condition, 3 centrifuge washings, removes unreacted 4-amino-3-hydrazine-5-and dredges base-1,2,4-triazole, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 5:1 measure aqueous solution containing sulfhydrylation Graphene and the methyl-silicone oil containing lomustine, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 400W power, ultrasonic irradiation 5min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 2
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the DIC of 50mg; At N
2under protection, add 2-amino-5-sulfydryl-1,3, the 4-thiadiazoles of 20mg, stirring reaction 8 hours under oxygen free condition, 5 centrifuge washings, remove unreacted 2-amino-5-sulfydryl-1,3,4-thiadiazoles, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 1:1 measure aqueous solution containing sulfhydrylation Graphene and the Oleum Helianthi containing lomustine, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 300W power, ultrasonic irradiation 18min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 3
By 5mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the dicyclohexylcarbodiimide of 20mg; At N
2under protection, add the cysteamine of 20mg, stirring reaction 12 hours under oxygen free condition, 3 centrifuge washings, remove unreacted cysteamine, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 10:1 measure aqueous solution containing sulfhydrylation Graphene and the fish oil containing paclitaxel, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 100W power, ultrasonic irradiation 20min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 4
By 20mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the aqueous solution containing 150mg1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride; At N
2under protection, add the cysteine of 50mg, stirring reaction 24 hours under oxygen free condition, 4 centrifuge washings, remove unreacted cysteine, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 15:1 measure aqueous solution containing sulfhydrylation Graphene and the Oleum Arachidis hypogaeae semen containing silymarin, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 200W power, ultrasonic irradiation 15min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 5
By 15mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the DIC of 120mg; At N
2under protection, add the homocysteine of 40mg; Stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted homocysteine, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 20:1 measure aqueous solution containing sulfhydrylation Graphene and the oil of the umbilicus of Semen Maydis containing paclitaxel, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 500W power, ultrasonic irradiation 13min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 6
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the dicyclohexylcarbodiimide of 120mg; At N
2under protection, add the glutathion of 30mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted glutathion, obtain sulfhydrylation Graphene.The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 5:1 measure aqueous solution containing sulfhydrylation Graphene and the fish oil containing camptothecine, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 600W power, ultrasonic irradiation 10min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 7
By 20mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the aqueous solution containing 150mg1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride; At N
2under protection, add the 2-sulfydryl-4-amino-6-hydroxy pyrimidine of 50mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 2-sulfydryl-4-amino-6-hydroxy pyrimidine, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 10:1 measure aqueous solution containing sulfhydrylation Graphene and the olive oil containing camptothecine, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 800W power, ultrasonic irradiation 6min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 8
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the DIC of 150mg; At N
2under protection, add 6-sulfydryl-2, the 4-di-amino-pyrimidine of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 6-sulfydryl-2,4-di-amino-pyrimidine, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 8:1 measure aqueous solution containing sulfhydrylation Graphene and the olive oil containing ginsenoside, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 700W power, ultrasonic irradiation 8min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 9
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the dicyclohexylcarbodiimide of 150mg; At N
2under protection, add the 1-amino-5-sulfydryl anthraquinone of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 1-amino-5-sulfydryl anthraquinone, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 13:1 measure aqueous solution containing sulfhydrylation Graphene and the hydroxy silicon oil containing camptothecine, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 900W power, ultrasonic irradiation 3min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 10
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the aqueous solution containing 100mg1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride; At N
2under protection, add the 2-amino-6-hydroxyl-8-purinethol of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 2-amino-6-hydroxyl-8-purinethol, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 4:1 measure aqueous solution containing sulfhydrylation Graphene and the methyl-silicone oil containing ginsenoside, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 500W power, ultrasonic irradiation 6min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 11
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the DIC of 100mg; At N
2under protection, add the 2-amino-Ismipur of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 2-amino-Ismipur, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 20:1 measure aqueous solution containing sulfhydrylation Graphene and the methyl-silicone oil containing paclitaxel, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 1000W power, ultrasonic irradiation 1min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 12
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the dicyclohexylcarbodiimide of 100mg; At N
2under protection, add 3-amino-5-sulfydryl-1,2, the 4-triazole of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 3-amino-5-sulfydryl-1,2,4-triazole, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 9:1 measure aqueous solution containing sulfhydrylation Graphene and the hydroxy silicon oil containing ginsenoside, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 850W power, ultrasonic irradiation 4min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 13
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the aqueous solution containing 120mg1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride; At N
2under protection, add the 2-amino-5-mercaptobenzoic acid of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 2-amino-5-mercaptobenzoic acid, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 12:1 measure aqueous solution containing sulfhydrylation Graphene and the Oleum Glycines containing silymarin, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 500W power, ultrasonic irradiation 8min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 14
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the DIC of 120mg; At N
2under protection, add 2-sulfydryl-4-amino-7H-pyrroles [2, the 3-d] pyrimidine of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 2-sulfydryl-4-amino-7H-pyrroles [2,3-d] pyrimidine, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 8:1 measure aqueous solution containing sulfhydrylation Graphene and the olive oil containing lomustine, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 100W power, ultrasonic irradiation 10min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 15
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the dicyclohexylcarbodiimide of 120mg; At N
2under protection, add the 3-amino-4-mercaptoquinoline of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 3-amino-4-mercaptoquinoline, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 1:1 measure aqueous solution containing sulfhydrylation Graphene and the oil of the umbilicus of Semen Maydis containing lomustine, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 300W power, ultrasonic irradiation 5min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 16
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the aqueous solution containing 150mg1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride; At N
2under protection, add the 4-amino-3-sulfydryl-4H-1 of 20mg, 2,4-triazole, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 4-amino-3-sulfydryl-4H-1,2,4-triazole, obtains sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 1:1 measure aqueous solution containing sulfhydrylation Graphene and the Oleum Glycines containing camptothecine, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 200W power, ultrasonic irradiation 16min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 17
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the DIC of 150mg; At N
2under protection, add the 2-amino-6-sulfydryl-3H-pyrimidin-4-one of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 2-amino-6-sulfydryl-3H-pyrimidin-4-one, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 4:1 measure aqueous solution containing sulfhydrylation Graphene and the hydroxy silicon oil containing paclitaxel, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 400W power, ultrasonic irradiation 10min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 18
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the dicyclohexylcarbodiimide of 150mg; At N
2under protection, add the amino-Polyethylene Glycol-sulfydryl of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted amino-Polyethylene Glycol-sulfydryl, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 6:1 measure aqueous solution containing sulfhydrylation Graphene and the Oleum Arachidis hypogaeae semen containing ginsenoside, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 600W power, ultrasonic irradiation 8min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 19
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the aqueous solution containing 100mg1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride; At N
2under protection, add the 5-amino-2-mercapto phenyl formic-4-thiazole carboxamides of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 5-amino-2-mercapto phenyl formic-4-thiazole carboxamides, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 15:1 measure aqueous solution containing sulfhydrylation Graphene and the Oleum Helianthi containing camptothecine, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 700W power, ultrasonic irradiation 6min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 20
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the DIC of 100mg; At N
2under protection, add the 2-amino-3-sulfydryl-3-methyl fourth carboxylic acid of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 2-amino-3-sulfydryl-3-methyl fourth carboxylic acid, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 8:1 measure aqueous solution containing sulfhydrylation Graphene and the fish oil containing ginsenoside, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 800W power, ultrasonic irradiation 5min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 21
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the dicyclohexylcarbodiimide of 100mg; At N
2under protection, add the 2-amino-3-sulfydryl-1-propanol of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 2-amino-3-sulfydryl-1-propanol, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 10:1 measure aqueous solution containing sulfhydrylation Graphene and the Oleum Arachidis hypogaeae semen containing lomustine, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 900W power, ultrasonic irradiation 2min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 22
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the aqueous solution containing 120mg1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride; At N
2under protection, add the 5-amino-2-mercapto phenyl formic thiazole of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 5-amino-2-mercapto phenyl formic thiazole, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 8:1 measure aqueous solution containing sulfhydrylation Graphene and the methyl-silicone oil containing silymarin, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 1000W power, ultrasonic irradiation 1min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 23
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the DIC of 120mg; At N
2under protection, add the sulfydryl undecylamine of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted sulfydryl undecylamine, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 5:1 measure aqueous solution containing sulfhydrylation Graphene and the Oleum Glycines containing paclitaxel, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 400W power, ultrasonic irradiation 3min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 24
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the aqueous solution containing 150mg1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride; At N
2under protection, add the 5-amino-1-mercaptopentane of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 5-amino-1-mercaptopentane, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 8:1 measure aqueous solution containing sulfhydrylation Graphene and the olive oil containing ginsenoside, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 500W power, ultrasonic irradiation 10min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Embodiment 25
By 10mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the dicyclohexylcarbodiimide of 120mg; At N
2under protection, add the 6-amino-1-mercapto hexane of 20mg, stirring reaction 24 hours under oxygen free condition, 3 centrifuge washings, remove unreacted 6-amino-1-mercapto hexane, obtain sulfhydrylation Graphene; The sulfhydrylation graphene uniform of preparation is scattered in deionized water; With test tube by volume 15:1 measure aqueous solution containing sulfhydrylation Graphene and the oil of the umbilicus of Semen Maydis containing camptothecine, be placed in ice-water bath; Ultrasonic probe is placed in oil/water two-phase interface, under 800W power, ultrasonic irradiation 10min; Centrifuge washing is carried out to reactant liquor, obtains functionalization graphene microcapsule.
Claims (7)
1. a cyst wall contains the microcapsule of functionalization graphene, it is characterized in that, by carrying out ultrasonic radiation to the aqueous solution simultaneously containing the sulfhydrylation Graphene obtained after sulfydryl and amino compound or biomolecule modification with the oil phase being mounted with hydrophobic drug, formed with the cross linking membrane of sulfhydrylation Graphene as cyst wall, to be loaded with the drug-loading microcapsule of oil phase for core of hydrophobic drug, the size of microcapsule is between 0.2-30 μm.
2. contain the microcapsule of functionalization graphene according to a kind of cyst wall according to claim 1, it is characterized in that, containing sulfydryl and amino compound or biomolecule while described is that 4-amino-3-hydrazine-5-dredges base-1,2,4-triazole, 2-sulfydryl-4-amino-6-hydroxy pyrimidine, 6-sulfydryl-2,4-di-amino-pyrimidine, 1-amino-5-sulfydryl anthraquinone, 2-amino-6-hydroxyl-8-purinethol, 2-amino-Ismipur, 3-amino-5-sulfydryl-1,2,4-triazole, 2-amino-5-mercaptobenzoic acid, 2-sulfydryl-4-amino-7H-pyrroles [2,3-d] pyrimidine, 3-amino-4-mercaptoquinoline, 4-amino-3-sulfydryl-4H-1,2,4-triazole, 2-amino-6-sulfydryl-3H-pyrimidin-4-one, amino-Polyethylene Glycol-sulfydryl, 5-amino-2-mercapto phenyl formic-4-thiazole carboxamides, 2-amino-3-sulfydryl-3-methyl fourth carboxylic acid, 2-amino-3-sulfydryl-1-propanol, 2-amino-5-sulfydryl-1,3,4-thiadiazoles, 5-amino-2-mercapto phenyl formic thiazole, sulfydryl undecylamine and hydrochlorate thereof, 5-amino-1-mercaptopentane and hydrochlorate thereof, 6-amino-1-mercapto hexane and hydrochlorate thereof, cysteamine and hydrochlorate thereof, cysteine and hydrochlorate thereof, homocysteine or glutathion.
3. contain the microcapsule of functionalization graphene according to a kind of cyst wall according to claim 1, it is characterized in that, described hydrophobic drug is one or more in paclitaxel, lomustine, ginsenoside, camptothecine or silymarin medicine.
4. the microcapsule of functionalization graphene is contained according to a kind of cyst wall according to claim 1, it is characterized in that, described oil phase is the immiscible nontoxic liquid state organics of the various animal oil of biological medicine, vegetable oil, microbial grease, mineral oil, silicone oil or other and water.
5. cyst wall contains a preparation method for the microcapsule of functionalization graphene, it is characterized in that, comprises the following steps:
A, by 5-20mg graphene oxide ultrasonic disperse in dimethyl formamide, and add the DIC of 20-150mg, dicyclohexylcarbodiimide or the aqueous solution containing 20-150mg1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride;
B, at N
2under protection, while adding 10-50mg, contain compound or the biomolecule of sulfydryl and amino;
Stirring reaction 2-24 hour under c, oxygen free condition, 3-5 centrifuge washing, removes unreacted simultaneously containing sulfydryl and amino compound or biomolecule, obtains sulfhydrylation Graphene;
D, the sulfhydrylation graphene uniform of preparation is scattered in deionized water, measures the aqueous solution of sulfhydrylation Graphene and the oil phase containing hydrophobic drug with test tube by certain volume ratio, be placed in ice-water bath;
E, ultrasonic probe is placed in oil/water two-phase interface, under certain ultrasonic power, acts on a period of time;
F, centrifuge washing is carried out to reactant liquor, obtain with the cross linking membrane of sulfhydrylation Graphene for cyst wall, the drug-loading microcapsule being core with the oil phase of hydrophobic drug.
6. contain the microcapsule of functionalization graphene according to a kind of cyst wall according to claim 5, it is characterized in that, the volume ratio of the described aqueous solution containing sulfhydrylation Graphene and the oil phase containing hydrophobic drug is 1:1-20:1.
7. contain the microcapsule of functionalization graphene according to a kind of cyst wall according to claim 5, it is characterized in that, described ultrasonic power is 20-1000W/cm
2, ultrasonic time is 0.5-20min.
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