CN107456577A - A kind of preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent - Google Patents

A kind of preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent Download PDF

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CN107456577A
CN107456577A CN201710694674.XA CN201710694674A CN107456577A CN 107456577 A CN107456577 A CN 107456577A CN 201710694674 A CN201710694674 A CN 201710694674A CN 107456577 A CN107456577 A CN 107456577A
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preparation
double
magnetic resonance
fluorine
mode magnetic
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CN107456577B (en
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徐祖顺
林乐平
阳哲
刘佩
喻鸣
喻一鸣
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Hubei University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • A61K49/12—Macromolecular compounds
    • A61K49/126—Linear polymers, e.g. dextran, inulin, PEG
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
    • A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
    • A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
    • A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
    • A61K49/1827—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
    • A61K49/1851—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule
    • A61K49/1854—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule the organic macromolecular compound being obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly(meth)acrylate, polyacrylamide, polyvinylpyrrolidone, polyvinylalcohol

Abstract

The invention discloses a kind of preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent, comprise the following steps：(1) the fluorine-containing paramagnetism amphipathic polymer of polymerisation in solution synthesizing betaine is passed through；(2) by the fluorine-containing paramagnetism amphipathic polymer of glycine betaine and MoS2Presoma is dissolved in a solvent, and the MoS of the fluorine-containing paramagnetism amphipathic polymer hydridization of glycine betaine is thermally decomposed to generate by microwave radiation technology2Nano-particle；By the nano-particle centrifuge washing of preparation, disperse again in aqueous.Preparation technology of the present invention is simple, repeatability is high；The hybridized nanometer particle diameter of preparation is small and homogeneous, and good dispersion, stability are high in aqueous, have good biocompatibility；Diagnosis and treatment unified platform is constructed, there is good T1‑T2Double mode MRI imaging effects and photo-thermal therapy effect.

Description

A kind of preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent
Technical field
The present invention relates to material science and bio-medical field, more particularly to one kind to be based on the fluorine-containing paramagnetism amphiphilic of glycine betaine Polymer hybrid MoS2T1-T2Double-mode magnetic resonance guides photo-thermal diagnosis agent and its microwave radiation technology preparation method.
Background technology
Magnetic resonance imaging (MRI) is a kind of real-time shadowgraph technique of non-intruding, high resolution and can to soft-tissue imaging, One of detection means most strong in contemporary clinical diagnosis is turned into.Different groups are improved clinically by injection MRI contrast agent The contrast knitted, highlight the difference between each tissue, there is provided more accurately diagnostic message.Contrast agent can be divided into longitudinal relaxation and make Shadow agent (T1) and transverse relaxation contrast agent (T2).Usual T1For observing anatomical structure, T2For tissues observed lesion.Clinically Make T with containing gadolinium compound1Contrast agent, use Fe3O4Nano-particle makees T2Contrast agent.In recent years, research find due to19F is in each tissue Middle content is extremely low, is almost disturbed without background signal, can be used as a kind of potential T2Contrast agent.19The medicine of F MRI tracers can be with The aggregation situation of reflection medicine in vivo, and the T containing gadolinium1Contrast agent can provide anatomy, the letter of physiology and biochemistry Number；Two kinds of signals can gather in same equipment, therefore the research for the Double-mode imaging that two kinds of contrast agent are combined has Significance.
Photo-thermal therapy (PTT) is referred to utilizing the material with high light thermal conversion efficiency, after tumor locus aggregation, used Near infrared light produces hyperthermia to kill the treatment method of tumour cell.Medical imaging modalities are combined with PTT, pass through shadow As judging whether medicine reaches lesions position, near infrared light photograph is carried out to lesions position in good time, so as to reaching best treatment Effect, the research of diagnosis and treatment unified platform is significant as structure.
Therefore, we have proposed a kind of preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent to solve above-mentioned ask Topic.
The content of the invention
Based on technical problem existing for background technology, the present invention proposes a kind of double-mode magnetic resonance guiding photo-thermal diagnosis agent Preparation method.
A kind of preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent proposed by the present invention, comprises the following steps：
(1) 1g methacrylic acid carboxylic acid glycine betaines, 0.8g Hexafluorobutyl mathacrylates and 0.2g Gd (AA) are weighed3Phen ultrasonic disperses add 0.06g initiators in 15mL solvents, stir 20-40min while leading to nitrogen, then heat up To 65-85 DEG C of reaction 12-36h, it is cooled to room temperature and is washed 3 times with tetrahydrofuran/n-hexane reprecipitation method, 30-50 DEG C of vacuum is dried It is dry standby.
(2) the fluorine-containing paramagnetism amphipathic polymer of glycine betaine for weighing 0.5g preparations is dissolved in a certain amount of solvent, is disperseed equal 0.25g MoS are added after even2Presoma dissolves.Then mixed liquor is put into progress microwave radiation technology thermal decomposition in microwave reactor. Disperse again in aqueous after ethanol/water centrifuge washing is used after solution cooling；The fluorine-containing paramagnetism two of glycine betaine is obtained Close polymer hybrid MoS2T1-T2Double-mode magnetic resonance photo-thermal diagnosis agent.
Preferably, the oil-soluble monomer of polymerisation in solution is Hexafluorobutyl mathacrylate, methacrylic acid in the step 1 One kind, water-soluble monomer in trifluoro ethyl ester be (methyl) acrylic acid carboxylic acid glycine betaine and (methyl) acrylic acid sulphonic acid betaine, One kind and functional monomer Gd (AA) in (methyl) acrylic acid phosphoric acid betaine3Phen.The three classes monomer is in mass ratio For (1-5)：5：1.
Preferably, the solvent of polymerisation in solution is methanol, ethanol, tetrahydrofuran, dimethyl sulfoxide (DMSO), diformazan in the step 1 One or more of mixed liquors in base formamide.
Preferably, the initiator of polymerisation in solution is azodiisobutyronitrile, ABVN, peroxidating in the step 1 One or more in dibenzoyl, dicetyl peroxydicarbonate ethylhexyl.
Preferably, MoS in the step 22The molybdenum source of presoma is sodium molybdate, ammonium molybdate, molybdenum chloride, four thio ammonium molybdate In one kind, sulphur source is thiocarbamide, thioacetamide, cysteine, one kind in four thio ammonium molybdate.
Preferably, MoS in the step 22The mass ratio of presoma and the fluorine-containing paramagnetism amphipathic polymer of glycine betaine is 1： (1-3)。
Preferably, solvent is in ethylene glycol, diethylene glycol, polyethylene glycol, oleic acid, oleyl amine, 1- octadecylenes in the step 2 One or more of mixed liquors.
Preferably, microwave radiation technology heat decomposition temperature is at 140-220 DEG C in the step 2, hour in reaction time 2-8.Use Reducing agent be hydrazine hydrate, one kind in hydroxylamine hydrochloride or without using reducing agent.
Beneficial effects of the present invention are as follows：
It is as follows compared to the good effect of prior art：
(1) preparation technology is simple, repeatability is high.
(2) the hybridized nanometer particle diameter prepared is small and homogeneous, and good dispersion, stability are high in aqueous, there have to be good Good biocompatibility.
(3) diagnosis and treatment unified platform is constructed, there is good T1-T2Double mode MRI imaging effects and photo-thermal therapy effect Fruit.
Brief description of the drawings
Fig. 1 is the scanning electron microscope diagram of hydridization molybdenum disulfide nano particle in embodiments of the invention 1；
Fig. 2 is the T of hydridization molybdenum disulfide nano particle dispersion in embodiments of the invention 11-T2Double mode MRI in vitro into As figure；
Fig. 3 is that hydridization molybdenum disulfide nano particle is 808nm with wavelength under various concentrations in this example 1 of the invention, Energy density is 1W/cm2Laser irradiates, and temperature is with irradiation time change curve.
Embodiment
The present invention is made with reference to specific embodiment further to explain.
Embodiment 1
(1) 1g methacrylic acid carboxylic acid glycine betaines, 0.8g Hexafluorobutyl mathacrylates and 0.2g Gd (AA) are weighed3Phen ultrasonic disperses add 0.06g azodiisobutyronitriles in 15mL methanol, stir 20min while leading to nitrogen, then 65 DEG C of reaction 12h are warming up to, room temperature is cooled to and is washed 3 times with tetrahydrofuran reprecipitation method, 30 DEG C of vacuum dryings are standby.
(2) the fluorine-containing paramagnetism amphipathic polymer of glycine betaine for weighing 0.5g preparations is dissolved in a certain amount of solvent, is disperseed equal 0.25g MoS are added after even2Presoma dissolves；Then mixed liquor is put into microwave reactor, in 140 DEG C of reaction 2h of 600W. Disperse again in aqueous after ethanol centrifuge washing is used after solution cooling.The fluorine-containing paramagnetism amphiphilic of glycine betaine has been obtained to gather Compound hydridization MoS2T1-T2Double-mode magnetic resonance photo-thermal diagnosis agent.
Wherein, the oil-soluble monomer of polymerisation in solution is Hexafluorobutyl mathacrylate, methacrylic acid three in the step 1 One kind, water-soluble monomer in fluorine ethyl ester are (methyl) acrylic acid carboxylic acid glycine betaine and (methyl) acrylic acid sulphonic acid betaine, (first Base) one kind and functional monomer Gd (AA) in acrylic acid phosphoric acid betaine3Phen.The three classes monomer is 1 in mass ratio： 5：1.
Wherein, MoS in the step 22The molybdenum source of presoma is in sodium molybdate, ammonium molybdate, molybdenum chloride, four thio ammonium molybdate One kind, sulphur source is thiocarbamide, thioacetamide, cysteine, one kind in four thio ammonium molybdate.
Wherein, MoS in the step 22The mass ratio of presoma and the fluorine-containing paramagnetism amphipathic polymer of glycine betaine is 1：1.
Wherein, the solvent in the step 2 is in ethylene glycol, diethylene glycol, polyethylene glycol, oleic acid, oleyl amine, 1- octadecylenes One or more of mixed liquors.
Wherein, in the step 2 the microwave reducing agent that uses of thermal decomposition be hydrazine hydrate, one kind in hydroxylamine hydrochloride or not Use reducing agent.
Embodiment 2
(1) 1g methacrylic acid carboxylic acid glycine betaines, 0.8g Hexafluorobutyl mathacrylates and 0.2g Gd (AA) are weighed3Phen ultrasonic disperses add 0.06g initiators in 15mL solvents, stir 25min while leading to nitrogen, then heat to 70 DEG C of reaction 18h, are cooled to room temperature and are washed 3 times with tetrahydrofuran reprecipitation method, 35 DEG C of vacuum dryings are standby.
(2) the fluorine-containing paramagnetism amphipathic polymer of glycine betaine for weighing 0.5g preparations is dissolved in a certain amount of solvent, is disperseed equal 0.25g MoS are added after even2Presoma dissolves.Then mixed liquor is put into microwave reactor, in 160 DEG C of reaction 4h of 700W. Disperse again in aqueous after water centrifuge washing is used after solution cooling.The fluorine-containing paramagnetism amphiphilic polymerization of glycine betaine is obtained Thing hydridization MoS2T1-T2Double-mode magnetic resonance photo-thermal diagnosis agent.
Wherein, the oil-soluble monomer of polymerisation in solution is Hexafluorobutyl mathacrylate, methacrylic acid three in the step 1 One kind, water-soluble monomer in fluorine ethyl ester are (methyl) acrylic acid carboxylic acid glycine betaine and (methyl) acrylic acid sulphonic acid betaine, (first Base) one kind and functional monomer Gd (AA) in acrylic acid phosphoric acid betaine3Phen.The three classes monomer is 2 in mass ratio： 5：1.
Wherein, the solvent of polymerisation in solution is methanol, ethanol, tetrahydrofuran, dimethyl sulfoxide (DMSO), dimethyl in the step 1 One or more of mixed liquors in formamide.
Wherein, the initiator of polymerisation in solution is azodiisobutyronitrile, ABVN, peroxidating two in the step 1 One or more in benzoyl, dicetyl peroxydicarbonate ethylhexyl.
Wherein, MoS in the step 22The molybdenum source of presoma is in sodium molybdate, ammonium molybdate, molybdenum chloride, four thio ammonium molybdate One kind, sulphur source is thiocarbamide, thioacetamide, cysteine, one kind in four thio ammonium molybdate.
Wherein, MoS in the step 22The mass ratio of presoma and the fluorine-containing paramagnetism amphipathic polymer of glycine betaine is 1：1.
Wherein, the solvent in the step 2 is in ethylene glycol, diethylene glycol, polyethylene glycol, oleic acid, oleyl amine, 1- octadecylenes One or more of mixed liquors.
Wherein, in the step 2 the microwave reducing agent that uses of thermal decomposition be hydrazine hydrate, one kind in hydroxylamine hydrochloride or not Use reducing agent.
Embodiment 3
(1) 1g methacrylic acid carboxylic acid glycine betaines, 0.8g Hexafluorobutyl mathacrylates and 0.2g Gd (AA) are weighed3Phen ultrasonic disperses add 0.06g initiators in 15mL solvents, stir 30min while leading to nitrogen, then heat to 75 DEG C of reaction 24h, are cooled to room temperature and are washed 3 times with tetrahydrofuran reprecipitation method, 40 DEG C of vacuum dryings are standby.
(2) the fluorine-containing paramagnetism amphipathic polymer of glycine betaine for weighing 0.5g preparations is dissolved in a certain amount of solvent, is disperseed equal 0.25g MoS are added after even2Presoma dissolves.Then mixed liquor is put into microwave reactor, in 180 DEG C of reaction 4h of 800W. Disperse again in aqueous after ethanol/water centrifuge washing is used after solution cooling.The fluorine-containing paramagnetism two of glycine betaine is obtained Close polymer hybrid MoS2T1-T2Double-mode magnetic resonance photo-thermal diagnosis agent.
Wherein, the oil-soluble monomer of polymerisation in solution is Hexafluorobutyl mathacrylate, methacrylic acid three in the step 1 One kind, water-soluble monomer in fluorine ethyl ester are (methyl) acrylic acid carboxylic acid glycine betaine and (methyl) acrylic acid sulphonic acid betaine, (first Base) one kind and functional monomer Gd (AA) in acrylic acid phosphoric acid betaine3Phen.The three classes monomer is 3 in mass ratio： 5：1.
Wherein, the solvent of polymerisation in solution is methanol, ethanol, tetrahydrofuran, dimethyl sulfoxide (DMSO), dimethyl in the step 1 One or more of mixed liquors in formamide.
Wherein, the initiator of polymerisation in solution is azodiisobutyronitrile, ABVN, peroxidating two in the step 1 One or more in benzoyl, dicetyl peroxydicarbonate ethylhexyl.
Wherein, MoS in the step 22The molybdenum source of presoma is in sodium molybdate, ammonium molybdate, molybdenum chloride, four thio ammonium molybdate One kind, sulphur source is thiocarbamide, thioacetamide, cysteine, one kind in four thio ammonium molybdate.
Wherein, MoS in the step 22The mass ratio of presoma and the fluorine-containing paramagnetism amphipathic polymer of glycine betaine is 1：2.
Wherein, the solvent in the step 2 is in ethylene glycol, diethylene glycol, polyethylene glycol, oleic acid, oleyl amine, 1- octadecylenes One or more of mixed liquors.
Wherein, in the step 2 the microwave reducing agent that uses of thermal decomposition be hydrazine hydrate, one kind in hydroxylamine hydrochloride or not Use reducing agent.
Embodiment 4
(1) 1g methacrylic acid carboxylic acid glycine betaines, 0.8g Hexafluorobutyl mathacrylates and 0.2g Gd (AA) are weighed3Phen ultrasonic disperses add 0.06g initiators in 15mL solvents, stir 35min while leading to nitrogen, then heat to 80 DEG C of reaction 30h, are cooled to room temperature and are washed 3 times with tetrahydrofuran/n-hexane reprecipitation method, 45 DEG C of vacuum dryings are standby.
(2) the fluorine-containing paramagnetism amphipathic polymer of glycine betaine for weighing 0.5g preparations is dissolved in a certain amount of solvent, is disperseed equal 0.25g MoS are added after even2Presoma dissolves.Then mixed liquor is put into microwave reactor, in 200 DEG C of reaction 6h of 900W. Disperse in aqueous, that is, to have obtained the fluorine-containing paramagnetism two of glycine betaine again after using ethanol/water centrifuge washing after solution cooling Close polymer hybrid MoS2T1-T2Double-mode magnetic resonance photo-thermal diagnosis agent.
Wherein, the oil-soluble monomer of polymerisation in solution is Hexafluorobutyl mathacrylate, methacrylic acid three in the step 1 One kind, water-soluble monomer in fluorine ethyl ester are (methyl) acrylic acid carboxylic acid glycine betaine and (methyl) acrylic acid sulphonic acid betaine, (first Base) one kind and functional monomer Gd (AA) in acrylic acid phosphoric acid betaine3Phen.The three classes monomer is 4 in mass ratio： 5：1.
Wherein, the solvent of polymerisation in solution is methanol, ethanol, tetrahydrofuran, dimethyl sulfoxide (DMSO), dimethyl in the step 1 One or more of mixed liquors in formamide.
Wherein, the initiator of polymerisation in solution is azodiisobutyronitrile, ABVN, peroxidating two in the step 1 One or more in benzoyl, dicetyl peroxydicarbonate ethylhexyl.
Wherein, MoS in the step 22The molybdenum source of presoma is in sodium molybdate, ammonium molybdate, molybdenum chloride, four thio ammonium molybdate One kind, sulphur source is thiocarbamide, thioacetamide, cysteine, one kind in four thio ammonium molybdate.
Wherein, MoS in the step 22The mass ratio of presoma and the fluorine-containing paramagnetism amphipathic polymer of glycine betaine is 1：3.
Wherein, the solvent in the step 2 is in ethylene glycol, diethylene glycol, polyethylene glycol, oleic acid, oleyl amine, 1- octadecylenes One or more of mixed liquors.
Wherein, in the step 2 the microwave reducing agent that uses of thermal decomposition be hydrazine hydrate, one kind in hydroxylamine hydrochloride or not Use reducing agent.
Embodiment 5
(1) 1g methacrylic acid carboxylic acid glycine betaines, 0.8g Hexafluorobutyl mathacrylates and 0.2g Gd (AA) are weighed3Phen ultrasonic disperses add 0.06g initiators in 15mL solvents, stir 40min while leading to nitrogen, then heat to 85 DEG C of reaction 36h, are cooled to room temperature and are washed 3 times with n-hexane reprecipitation method, 50 DEG C of vacuum dryings are standby.
(2) the fluorine-containing paramagnetism amphipathic polymer of glycine betaine for weighing 0.5g preparations is dissolved in a certain amount of solvent, is disperseed equal 0.25g MoS are added after even2Presoma dissolves.Then mixed liquor is put into microwave reactor, in 220 DEG C of reaction 8h of 800W. Disperse again in aqueous after water centrifuge washing is used after solution cooling.The fluorine-containing paramagnetism amphiphilic polymerization of glycine betaine is obtained Thing hydridization MoS2T1-T2Double-mode magnetic resonance photo-thermal diagnosis agent.
Wherein, the oil-soluble monomer of polymerisation in solution is Hexafluorobutyl mathacrylate, methacrylic acid three in the step 1 One kind, water-soluble monomer in fluorine ethyl ester are (methyl) acrylic acid carboxylic acid glycine betaine and (methyl) acrylic acid sulphonic acid betaine, (first Base) one kind and functional monomer Gd (AA) in acrylic acid phosphoric acid betaine3Phen.The three classes monomer is 5 in mass ratio： 5：1.
Wherein, the solvent of polymerisation in solution is methanol, ethanol, tetrahydrofuran, dimethyl sulfoxide (DMSO), dimethyl in the step 1 One or more of mixed liquors in formamide.
Wherein, the initiator of polymerisation in solution is azodiisobutyronitrile, ABVN, peroxidating two in the step 1 One or more in benzoyl, dicetyl peroxydicarbonate ethylhexyl.
Wherein, MoS in the step 22The molybdenum source of presoma is in sodium molybdate, ammonium molybdate, molybdenum chloride, four thio ammonium molybdate One kind, sulphur source is thiocarbamide, thioacetamide, cysteine, one kind in four thio ammonium molybdate.
Wherein, MoS in the step 22The mass ratio of presoma and the fluorine-containing paramagnetism amphipathic polymer of glycine betaine is 1：3.
Wherein, the solvent in the step 2 is in ethylene glycol, diethylene glycol, polyethylene glycol, oleic acid, oleyl amine, 1- octadecylenes One or more of mixed liquors.
Wherein, in the step 2 the microwave reducing agent that uses of thermal decomposition be hydrazine hydrate, one kind in hydroxylamine hydrochloride or not Use reducing agent.
The foregoing is only a preferred embodiment of the present invention, but protection scope of the present invention be not limited thereto, Any one skilled in the art the invention discloses technical scope in, technique according to the invention scheme and its Inventive concept is subject to equivalent substitution or change, should all be included within the scope of the present invention.

Claims (8)

1. a kind of preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent, it is characterised in that comprise the following steps：
(1) the fluorine-containing paramagnetism amphipathic polymer of polymerisation in solution synthesizing betaine is passed through；
(2) by the fluorine-containing paramagnetism amphipathic polymer of glycine betaine and MoS2Presoma dissolves in a solvent, is thermally decomposed by microwave radiation technology Generate the MoS of the fluorine-containing paramagnetism amphipathic polymer hydridization of glycine betaine2Nano-particle；By the nano-particle centrifuge washing of preparation, weight It is new to disperse in aqueous.
A kind of 2. preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent according to claim 1, it is characterised in that The oil-soluble monomer of polymerisation in solution is one in Hexafluorobutyl mathacrylate, trifluoroethyl methacrylate in the step 1 Kind, water-soluble monomer are (methyl) acrylic acid carboxylic acid glycine betaine and (methyl) acrylic acid sulphonic acid betaine, (methyl) acrylic acid phosphorus One kind and functional monomer Gd (AA) in sour glycine betaine3Phen.The three classes monomer is (1-5) in mass ratio：5：1.
A kind of 3. preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent according to claim 1, it is characterised in that The solvent of polymerisation in solution is one kind in methanol, ethanol, tetrahydrofuran, dimethyl sulfoxide (DMSO), dimethylformamide in the step 1 Or several mixed liquors.
A kind of 4. preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent according to claim 2, it is characterised in that The initiator of polymerisation in solution is azodiisobutyronitrile, ABVN, dibenzoyl peroxide, peroxidating in the step 1 One or more in two diethyl hexylcarbonates.
A kind of 5. preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent according to claim 1, it is characterised in that MoS in the step 22The molybdenum source of presoma is one kind in sodium molybdate, ammonium molybdate, molybdenum chloride, four thio ammonium molybdate, and sulphur source is One kind in thiocarbamide, thioacetamide, cysteine, four thio ammonium molybdate.
A kind of 6. preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent according to claim 4, it is characterised in that MoS in the step 22The mass ratio of presoma and the fluorine-containing paramagnetism amphipathic polymer of glycine betaine is 1：(1-3).
A kind of 7. preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent according to claim 5, it is characterised in that Solvent is that the one or more in ethylene glycol, diethylene glycol, polyethylene glycol, oleic acid, oleyl amine, 1- octadecylenes are mixed in the step 2 Close liquid.
A kind of 8. preparation method of double-mode magnetic resonance guiding photo-thermal diagnosis agent according to claim 6, it is characterised in that For microwave radiation technology heat decomposition temperature at 140-220 DEG C, hour in reaction time 2-8, the reducing agent used is hydration in the step 2 One kind in hydrazine, hydroxylamine hydrochloride or without using reducing agent.
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CN109395107A (en) * 2018-12-25 2019-03-01 上海纳米技术及应用国家工程研究中心有限公司 The preparation method and products thereof of the difunctional two-dimension nano materials of ultrasound-thermotherapy
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CN110559439A (en) * 2019-10-15 2019-12-13 上海纳米技术及应用国家工程研究中心有限公司 Preparation method of photo-thermal and photodynamic cooperative therapeutic agent

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Publication number Priority date Publication date Assignee Title
CN109395107A (en) * 2018-12-25 2019-03-01 上海纳米技术及应用国家工程研究中心有限公司 The preparation method and products thereof of the difunctional two-dimension nano materials of ultrasound-thermotherapy
CN109821031A (en) * 2019-02-01 2019-05-31 中国医学科学院生物医学工程研究所 The synthesis and application of fluoro- 19 magnetic resonance imaging contrast of carboxylic acid glycine betaine amphoteric ion polymer
CN110559439A (en) * 2019-10-15 2019-12-13 上海纳米技术及应用国家工程研究中心有限公司 Preparation method of photo-thermal and photodynamic cooperative therapeutic agent

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