CN104623659A - Preparation method of multifunctional probe for tumor thermotherapy as magnetic resonance imaging contrast agent - Google Patents
Preparation method of multifunctional probe for tumor thermotherapy as magnetic resonance imaging contrast agent Download PDFInfo
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Abstract
The invention provides a preparation method of a multifunctional probe for tumor thermotherapy as a magnetic resonance imaging contrast agent. The preparation method of the multifunctional probe comprises the following steps: dropwise adding the solution of sodium diethyldithiocarbamate of water into the solution of a copper compound in water, stirring to obtain a blackish brown precipitate which is diethyl dithio amino copper, and drying the precipitate in vacuum; adding a diethyl dithio amino copper containing solution of oleylamine into hot oleylamine, introducing nitrogen into the mixture, heating the mixture, stirring, cooling to room temperature, washing, centrifuging, dispersing into a stabilizer, and evaporating in a rotating way; adding a surfactant, stirring, and filtering to obtain a transparent blackish green solution; adding ethanol into the blackish green solution, oscillating ultrasonically, stirring, adding an alkali, a silicon source and a magnetic compound, and stirring to form nanoparticles in core-shell structures. The probe heats tissues by adopting the heat effect generated in the tissues of a human body by a variety of physical energy such as microwaves, radio frequency and ultrasonic waves to accelerate the death of tumour cells, and the probe can be used as the magnetic resonance imaging contrast agent.
Description
Technical field
The present invention relates to the preparation field of nano material, relate to the preparation method of a kind of tumor thermotherapy and magnetic resonance contrast agent multiprobe particularly.
Background technology
Tumor thermotherapy is development in recent years a kind of oncotherapy means faster, refers to its heat effect by various pyrogen, is heated to effectively treat temperature range in tumor area or whole body, and maintains certain hour with a kind of Therapeutic Method of killing off tumor cells.Thermotherapy is as a kind of physical therapy modalities, and it is noinvasive or Wicresoft that same chemotherapy, radiotherapy compare its great advantage, can effective reduction of patient pain, improves patients ' life quality number.At present, the application prospect of thermotherapy in oncotherapy is confirmed, it can be able to make the tumor blood vessels of original slow blood flow be retarded by silt by heating, the temperature of tumor tissues is caused to close on normal structure higher than tumor, its temperature difference can reach 5 ~ 10 DEG C, this temperature official post heat energy kills cancerous cell and don't meeting damaging normal tissue cells (Ino A, ShinKai M, Honda H, eat al.Heat shock protein 70expression induces antitumor immunity during intra-celluar hypert hermia using magnetie nano-particles [J] .Cancer Immunol Immunother, 2003, 52 (2): 80-88).The key of effective thermotherapy is exactly the heat production material selecting to be applicable to.Desirable heat production material should have high heat production rate, stability and biocompatibility, and the material for thermotherapy the earliest mainly comprises magnetic iron ore (Fe
3o
4) and bloodstone (Fe
2o
3).Current research shows, a kind of nano material-Cu9S5 of novelty, has strong absorption effect near infrared region to laser energy, and light energy is converted into heat energy rapidly, and the heat effect of generation result in the collapse at once of cell.At present, the nano material of this novelty, because of the near-infrared absorption of its uniqueness and light stability, can replace the application of light absorbing dyestuff in laserthermia effectively.As people (Tian Q such as Q Tian, Jiang F, Zou R, et al.Hydrophilic Cu9S5nanocrystals:A photothermal agent with a 25.7%heat conversion efficiency for photothermal ablation of cancer cells in vivo [J] .Acs Nano, 2011,5 (12): 9761-9771.) hydrophilic cu9s5 has been synthesized nanocrystalline.This is nanocrystalline has obvious light absorption in the whole region of 400 ~ 1100nm, presents in the absorption intensity in near-infrared (600 ~ 1100nm) region the trend strengthened gradually, and this nanocrystallinely has very high photothermal deformation rate (25.7%)
The design and devdlop of multiprobe is one of forward position study hotspot of nano biological medical domain.At present based on the mentality of designing of the multiprobe of cancer diagnosis and treatment, usually " block combiner " thinking is followed, be about to the module (as diagnostic module and treatment module) with difference in functionality, combined by certain mode and concentrate in a nanoscale carrier.At present, report probe (the Tian Q with Cu9S5 and the Fe3O4 thermotherapy that is medium and diagnosis, Hu J, Zhu Y, et al.Sub-10nm Fe3O4@Cu2 – x S Core – Shell Nanoparticles for Dual-Modal Imaging and Photothermal Therapy [J] .Journal of the American Chemical Society, 2013,135 (23): 8571-8577.), but this probe is negative contrast medium, easily produce blurring with tissue, and preparation process is complicated.
Summary of the invention
For defect of the prior art, based on the most widely used clinical opaque contrast medium, provide the preparation method of a kind of tumor thermotherapy and magnetic resonance contrast agent multiprobe.The method first synthesizes the Cu9S5 precursor with thermotherapy effect, then at the meso-porous titanium dioxide silicon structure of its outside synthesizing blender magnetic compound, forms nucleocapsid structure, have the multi-functional diagnosis and treatment probe of thermotherapy and nuclear magnetic resonance.This technology preparation method is simple, and the product stability of gained is good, can meet the demand of clinical practice.
For realizing such object, in the inventive solutions, with sodium diethyldithiocarbamate and copper compound and oleyl amine for precursor synthesis has the Cu9S5 of thermotherapeutic function, take surfactant as assist medium, by adding alkali, silicon source synthesis shell structure, adds magnetic ion simultaneously and participates in hydrolysis, realize the function of magnetic resonance contrast agent thus.
Method of the present invention comprises the steps:
A. be in the deionized water of 500 ~ 600 parts at mass fraction, add 20 ~ 50 parts of sodium diethyldithiocarbamates; Be in the deionized water of 500 ~ 600 parts at mass fraction, add 40 ~ 100 parts of copper compounds, sodium diethyldithiocarbamate aqueous solution is slowly dripped in copper compound aqueous solution;
B. at room temperature magnetic agitation, generates pitchy muddy;
C. the pitchy of b gained muddiness being joined mass fraction is in the oleyl amine of 10 ~ 50 parts;
D. be that 30 ~ 150 parts of oleyl amines load in container by mass fraction, 80 ~ 100 DEG C of heating, and pass into nitrogen removal dampness and oxygen, subsequently the solution that c obtains is added in container, be heated to more than 300 DEG C, magnetic agitation, be cooled to room temperature subsequently, centrifugal, by washing with alcohol, with 100 ~ 150 parts of dispersant;
E. will be that 100 ~ 120 parts of surfactants and 1000 ~ 1500 parts of water mix with mass fraction containing the solution obtained in 10 parts of above-mentioned d, the temperature magnetic agitation more than 40 DEG C, subsequently by the evaporation of gained solution rotating, dispersant evaporates from solution;
F. the solution membrane filtration will obtained in e, obtaining mass fraction is 10 ~ 20 parts of solution, with 100 ~ 200 parts of deionized water dispersions, is now blackish green solution;
G. be that 5 ~ 10 parts of ethanol add in the solution that above-mentioned f obtains by mass fraction, ultrasonic at least 1 hour, and stir more than 60 DEG C;
H. be 1 ~ 2 part of alkali by mass fraction, 2 ~ 3 parts of silicon sources, 1 ~ 2 part of magnetic compound joins in the solution of above-mentioned g gained, and more than 60 DEG C temperature stir at least 1 hour;
I. by after above-mentioned h gained solution centrifugal, adding mass fraction is 100 ~ 200 parts of ethanol, 1 ~ 2 part of ammonium nitrate, refluxes and stirs after at least 1 hour and removed surfactant, obtain tumor thermotherapy and magnetic resonance contrast agent multiprobe at 60 ~ 80 DEG C.
Preferably, described copper compound is at least one of cupric oxalate, Copper diiodide, Hydro-Giene (Water Science)., copper fluoride, copper fluoride, cupric perchlorate, cupric perchlorate, copper chlorate, Tubercuprose., cupric tartrate, cupric phosphate, Cupric fluosilicate, cupric fluosilicate, copper sulfide, cuprous sulfide, cupric thiocyanate, Cuprous sulfocyanate, cupric tetramminosulfate, copper sulfate, copper chloride, Cu-lyt., copper citrate, copper metaborate, Copper hydrate, copper cyanider, copper salicylate, and the effect of copper compound is the Cu that synthesis has thermotherapy effect
9s
5.
Preferably, described dispersant is at least one in stearmide, higher alcohol, vinyl bis-stearamides, glycerol monostearate, liquid paraffin, microcrystalline wax, barium stearate, chloroform, class of department 80, class 60 of department, Tween 80, tocopherol, and the effect of dispersant is that nano-particle is in a solvent dispersed.
Preferably, described surfactant is at least one in hyaluronic acid, cetyl trimethyl ammonium bromide, Dodecyl trimethyl ammonium chloride, DDA, sodium lauryl sulphate, dodecyl sodium sulfate, alevaire, dodecylbenzene sodium sulfonate, Triton X-100, polyoxyethylenesorbitan sorbitan monooleate, sorbitan monostearate, fatty acid distribution of coconut oil diglycollic amide, fatty alcohol-polyoxyethylene ether, polyoxyethylene lauryl ether, and the effect of surfactant is the dissolubility increasing chemical reagent.
Preferably, the described alkali stated is at least one in potassium hydroxide, sodium hydroxide, ammonia, calcium hydroxide, barium hydroxide, Copper hydrate, magnesium hydroxide, ferrous hydroxide, hydrated ferric oxide., aluminium hydroxide, and the effect of alkali is that the pH value of solution is adjusted to alkalescence.
Preferably, described magnetic compound is at least one in manganese dioxide, mangano-manganic oxide, manganese chloride, manganese sulfate, calcium chromate, manganess carbide, calcium acetate, potassium permanganate, Gadolinium trichloride, Digadolinium trisulfate, Gadolinia., ferroso-ferric oxide, oxygen ferrous iron, ferroso-ferric oxide, ferrum oxide, ferrous hydroxide, hydrated ferric oxide., ferrous sulfate and iron chloride, and the effect of magnetic compound is to provide has nuclear magnetic resonance reinforced effects magnetic ion.
Preferably, described silicon source is silicon monoxide, trichlorosilane, white carbon, silicon disulfide, orthosilicic acid, Silicon fluoride., Silicon chloride., Silicon bromide., silicon tetraiodide, 1,1,3, at least one in 3-tetramethyl-disilazane, N-trimethyl silicon based imidazole, monosilane, Disilicoethane, Trisilicopropane, isobutyl silane, positive penta silane, ring penta silane, white carbon, silicon source act as the raw material that mesoporous silicon oxide is provided.
Preferably, in above-mentioned steps b, room temperature lower magnetic force mixing time at least 4 hours, is preferably 4 ~ 6 hours.
Preferably, in above-mentioned steps d, more than 20 minutes heat time heating time, twice heating-up temperature is respectively 80 DEG C, 300 ~ 350 DEG C, and the magnetic agitation time is 20 ~ 40 minutes.Centrifugal condition is 10000 ~ 12000 turns.
Preferably, in above-mentioned steps e, temperature is 40 ~ 60 DEG C, at least 48 hours magnetic agitation time, is preferably 48 ~ 72 hours, and rotating evaporation temperature requires more than 40 ~ 50 DEG C.
Preferably, in above-mentioned steps g, adopt the filter membrane of 0.22 ~ 0.45 μm.
Preferably, in above-mentioned steps g, temperature is 60 ~ 80 DEG C, at least 1 hour magnetic agitation time, is preferably 1 ~ 2 hour, ultrasonic 1 ~ 2 hour.
Preferably, in above-mentioned steps h, temperature is 60 ~ 80 DEG C, and the magnetic agitation time is 1 ~ 2 hour.
Preferably, in above-mentioned steps i, temperature is more than 60 ~ 80 DEG C, and return time is 1 ~ 2 hour.
Compared with prior art, the present invention has following beneficial effect:
The invention has the advantages that technology preparation method is simple, the product nucleocapsid structure good stability of gained, biocompatibility is good, easy metabolism.Realize magnetic resonance make signal strengthen while, tumor is had to the therapeutic effect of thermotherapy.
Accompanying drawing explanation
By reading the detailed description done non-limiting example with reference to the following drawings, other features, objects and advantages of the present invention will become more obvious:
Fig. 1 is the external nuclear magnetic resonance of this contrast agent of variable concentrations in the embodiment of the present invention;
Fig. 2 is magnetic resonance contrast agent Tu popliteal nest contrast imaging figure in the embodiment of the present invention;
Fig. 3 is the TEM figure of multiprobe in the embodiment of the present invention.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is described in detail.Following examples will contribute to those skilled in the art and understand the present invention further, but not limit the present invention in any form.It should be pointed out that to those skilled in the art, without departing from the inventive concept of the premise, some distortion and improvement can also be made.These all belong to protection scope of the present invention.
Embodiment 1
A, be, in the deionized water of 520 parts, add 20 parts of sodium diethyldithiocarbamates at mass fraction; Be in the deionized water of 520 parts at mass fraction, add 40 parts of copper compounds, sodium diethyldithiocarbamate aqueous solution is slowly dripped in copper compound aqueous solution;
B, at room temperature magnetic agitation 4 hours, generate pitchy muddy;
C, the precipitation of b gained is joined mass fraction is in the oleyl amine of 10 parts, continues to stir;
D, be that 30 parts of oleyl amines load in flasks by mass fraction, 80 DEG C of heating 20 minutes, and pass into nitrogen and remove dampness and oxygen, subsequently the solution that c obtains is added in flask, be heated to 300 DEG C, magnetic agitation 20 minutes.Be cooled to room temperature subsequently, centrifugal 10000 turns, by washing with alcohol, 100 parts of chloroform dispersions;
E, will be that 100 parts of surfactants and 1000 points of water mix with mass fraction containing the solution obtained in 10 parts of above-mentioned d, stir 48 hours at 40 DEG C of lower magnetic forces, subsequently by gained solution 40 rotary evaporation, chloroform can evaporate from solution;
F, by the solution that obtains in the e membrane filtration with 0.225 μm, obtaining mass fraction is 10 parts of solution, with 100 parts of deionized waters dispersions, is now blackish green solution;
G, be that 5 parts of ethanol add in above-mentioned solution by mass fraction, ultrasonic 1 hour, and stir 1 hour at 60 DEG C;
H, be 1 part of alkali by mass fraction, 2 parts of silicon sources, 1 part of manganese chloride joins in the solution of g gained, stirs 1 hour at 60 DEG C;
I, by after h gained solution centrifugal, adding mass fraction is 100 parts of ethanol, 1 part of ammonium nitrate, refluxes and is removed surfactant after stirring 1 hour, obtain tumor thermotherapy and magnetic resonance contrast agent multiprobe at 60 DEG C.
Embodiment 2
A, be, in the deionized water of 540 parts, add 40 parts of sodium diethyldithiocarbamates at mass fraction; Be in the deionized water of 540 at mass fraction, add 60 parts of copper compounds, sodium diethyldithiocarbamate aqueous solution is slowly dripped in copper compound aqueous solution;
B, at room temperature magnetic agitation 5 hours, generate pitchy muddy;
C, the precipitation of b gained is joined mass fraction is in the oleyl amine of 30 parts, continues to stir;
D, mass fraction 100 parts of oleyl amines are loaded in flasks, 85 DEG C of heating 30 minutes, and pass into nitrogen and remove dampness and oxygen, subsequently the solution that c obtains is added in flask, be heated to 300 DEG C, magnetic agitation 20 ~ 40 minutes.Be cooled to room temperature subsequently, centrifugal 10000 turns, by washing with alcohol, 110 parts of chloroform dispersions;
E, will be that 110 parts of surfactants and 1200 parts of water mix with mass fraction containing the solution obtained in 10 parts of above-mentioned d, stir 72 hours at 50 DEG C of lower magnetic forces, subsequently by gained solution 40 DEG C of rotary evaporations, chloroform can evaporate from solution;
F, by the solution that obtains in the e membrane filtration with 0.22 μm, obtaining mass fraction is 15 parts of solution, with 150 parts of deionized waters dispersions, is now blackish green solution;
G, be that 8 parts of ethanol add in above-mentioned solution by mass fraction, ultrasonic 2 hours, and stir 1 ~ 2 hour at 70 DEG C;
H. be 2 parts of alkali by mass fraction, 3 parts of silicon sources, 2 parts of manganese chlorides join in the solution of g gained, stir 1 ~ 2 hour at 70 DEG C;
I, by after h gained solution centrifugal, adding mass fraction is 150 parts of ethanol, 1 ~ 2 part of ammonium nitrate, refluxes and is removed surfactant after stirring 1 ~ 2 hour, obtain tumor thermotherapy and magnetic resonance contrast agent multiprobe at 70 DEG C.
Embodiment 3
A, be, in the deionized water of 550 parts, add 50 parts of sodium diethyldithiocarbamates at mass fraction; Be in the deionized water of 550 parts at mass fraction, add 60 parts of copper compounds, sodium diethyldithiocarbamate aqueous solution is slowly dripped in copper compound aqueous solution;
B, at room temperature magnetic agitation 6 hours, generate pitchy muddy;
C, the precipitation of b gained is joined mass fraction is in the oleyl amine of 50 parts, continues to stir;
D, be that 100 parts of oleyl amines load in flasks by mass fraction, 80 DEG C of heating 40 minutes, and pass into nitrogen and remove dampness and oxygen, subsequently the solution that c obtains is added in flask, be heated to 300 DEG C, magnetic agitation 40 minutes.Be cooled to room temperature subsequently, centrifugal 12000 turns, by washing with alcohol, 150 parts of chloroform dispersions;
E, will be that 120 parts of surfactants and 1500 parts of water mix with mass fraction containing the solution obtained in 10 parts of above-mentioned d, stir 72 hours at 60 DEG C of lower magnetic forces, subsequently by gained solution 50 DEG C of rotary evaporations, chloroform can evaporate from solution;
F, by the solution that obtains in the e membrane filtration with 0.45 μm, obtaining mass fraction is 20 parts of solution, with 200 parts of deionized waters dispersions, is now blackish green solution;
G, be that 10 parts of ethanol add in above-mentioned solution by mass fraction, ultrasonic 2 hours, and stir 1 hour at 80 DEG C;
H, be 1 part of alkali by mass fraction, 2 parts of silicon sources, 2 parts of manganese chlorides join in the solution of g gained, stir 2 hours at 80 DEG C;
I, by after h gained solution centrifugal, adding mass fraction is 200 parts of ethanol, 2 parts of ammonium nitrates, refluxes and is removed surfactant after stirring 2 hours, obtain tumor thermotherapy and magnetic resonance contrast agent multiprobe at 80 DEG C.
Embodiment 4
A, mass fraction are in the deionized water of 500 parts, add 20 parts of sodium diethyldithiocarbamates; Be in the deionized water of 500 parts at mass fraction, add 80 parts of copper compounds, sodium diethyldithiocarbamate aqueous solution is slowly dripped in copper compound aqueous solution;
B, at room temperature magnetic agitation 6 hours, generate pitchy muddy;
C, the precipitation of b gained is joined mass fraction is in the oleyl amine of 50 parts, continues to stir;
D, be that 1200 parts of oleyl amines load in flasks by mass fraction, 90 DEG C of heating 20 minutes, and pass into nitrogen and remove dampness and oxygen, subsequently the solution that c obtains is added in flask, be heated to 300 DEG C, magnetic agitation 40 minutes.Be cooled to room temperature subsequently, centrifugal 12000 turns, by washing with alcohol, 100 parts of chloroform dispersions;
E, will be that 120 parts of surfactants, 1500 parts of water mix with mass fraction containing the solution obtained in 10 parts of above-mentioned d, stir 72 hours at 50 DEG C of lower magnetic forces, subsequently by gained solution 50 DEG C of rotary evaporations, chloroform can evaporate from solution;
F, by the solution that obtains in the e membrane filtration with 0.45 μm, obtaining mass fraction is 15 parts of solution, with 160 parts of deionized waters dispersions, is now blackish green solution;
G, be that 5 parts of ethanol add in above-mentioned solution by mass fraction, ultrasonic 1 hour, and stir 1 hour at 60 DEG C;
H, be 2 parts of alkali by mass fraction, 3 parts of silicon sources, 2 parts of manganese chlorides join in the solution of g gained, stir 1 hour at 80 DEG C;
I, by after h gained solution centrifugal, adding mass fraction is 100 parts of ethanol, 2 parts of ammonium nitrates, refluxes and is removed surfactant after stirring 1 hour, obtain tumor thermotherapy and magnetic resonance contrast agent multiprobe at 80 DEG C.
Embodiment 5
A, be, in the deionized water of 570 parts, add 30 parts of sodium diethyldithiocarbamates at mass fraction; Be in the deionized water of 570 parts at mass fraction, add 70 parts of copper compounds, sodium diethyldithiocarbamate aqueous solution is slowly dripped in copper compound aqueous solution;
B, at room temperature magnetic agitation 6 hours, generate pitchy muddy;
C, the precipitation of b gained is joined mass fraction is in the oleyl amine of 35 parts, continues to stir;
D, be that 100 parts of oleyl amines load in flasks by mass fraction, 90 DEG C of heating 35 minutes, and pass into nitrogen and remove dampness and oxygen, subsequently the solution that c obtains is added in flask, be heated to 300 DEG C, magnetic agitation 25 minutes.Be cooled to room temperature subsequently, centrifugal 11000 turns, by washing with alcohol, 135 parts of chloroform dispersions;
E, will be that 115 parts of surfactants and 1400 parts of water mix with mass fraction containing the solution obtained in 10 parts of above-mentioned d, stir 6 hours at 55 DEG C of lower magnetic forces, subsequently by gained solution 40 DEG C of rotary evaporations, chloroform can evaporate from solution;
F, by the solution that obtains in the e membrane filtration with 0.22 μm, obtaining mass fraction is 16 parts of solution, with 130 parts of deionized waters dispersions, is now blackish green solution;
G, be that 5 parts of ethanol add in above-mentioned solution by mass fraction, ultrasonic 1 hour, and stir 1 hour at 60 DEG C;
H, be 1 part of alkali by mass fraction, 2 parts of silicon sources, 1 part of manganese chloride joins in the solution of g gained, stirs 2 hours at 60 DEG C;
I, by after h gained solution centrifugal, adding mass fraction is 100 parts of ethanol, 1 part of ammonium nitrate, refluxes and is removed surfactant after stirring 1 hour, obtain tumor thermotherapy and magnetic resonance contrast agent multiprobe at 80 DEG C.
The inventive method first synthesizes the Cu9S5 precursor with thermotherapy effect, then at the meso-porous titanium dioxide silicon structure of its outside synthesizing blender magnetic compound, forms nucleocapsid structure, have the multi-functional diagnosis and treatment probe of thermotherapy and nuclear magnetic resonance.This technology preparation method is simple, and the product stability of gained is good, can meet the demand of clinical practice.
Above specific embodiments of the invention are described.It is to be appreciated that the present invention is not limited to above-mentioned particular implementation, those skilled in the art can make various distortion or amendment within the scope of the claims, and this does not affect flesh and blood of the present invention.
Claims (12)
1., by a preparation method for tumor thermotherapy and magnetic resonance contrast agent multiprobe, it is characterized in that the method comprises the steps:
A. be in the deionized water of 500 ~ 600 parts at mass fraction, add 20 ~ 50 parts of sodium diethyldithiocarbamates; Be in the deionized water of 500 ~ 600 parts at mass fraction, add 40 ~ 100 parts of copper compounds, sodium diethyldithiocarbamate aqueous solution is slowly dripped in copper compound aqueous solution;
B. at room temperature magnetic agitation, generates pitchy muddy;
C. the pitchy of b gained muddiness being joined mass fraction is in the oleyl amine of 10 ~ 50 parts;
D. be that 30 ~ 150 parts of oleyl amines load in container by mass fraction, 80 ~ 100 DEG C of heating, and pass into nitrogen removal dampness and oxygen, subsequently the solution that c obtains is added in container, be heated to more than 300 DEG C, magnetic agitation, be cooled to room temperature subsequently, centrifugal, by washing with alcohol, with 100 ~ 150 parts of dispersant;
E. will be that 100 ~ 120 parts of surfactants and 1000 ~ 1500 parts of water mix with mass fraction containing the solution obtained in 10 parts of above-mentioned d, the temperature magnetic agitation more than 40 DEG C, subsequently by the evaporation of gained solution rotating, dispersant evaporates from solution;
F. the solution membrane filtration will obtained in e, obtaining mass fraction is 10 ~ 20 parts of solution, with 100 ~ 200 parts of deionized water dispersions, is now blackish green solution;
G. be that 5 ~ 10 parts of ethanol add in the solution that above-mentioned f obtains by mass fraction, ultrasonic at least 1 hour, and at least 1 hour is stirred more than 60 DEG C;
H. be 1 ~ 2 part of alkali by mass fraction, 2 ~ 3 parts of silicon sources, 1 ~ 2 part of magnetic compound joins in the solution of above-mentioned g gained, and more than 60 DEG C temperature stir at least 1 hour;
I. by after above-mentioned h gained solution centrifugal, adding mass fraction is 100 ~ 200 parts of ethanol, 1 ~ 2 part of ammonium nitrate, refluxes and stirs after at least 1 hour and removed surfactant at 60 ~ 80 DEG C.
2. the preparation method of a kind of tumor thermotherapy according to claim 1 and magnetic resonance contrast agent multiprobe, it is characterized in that described copper compound is cupric oxalate, Copper diiodide, Hydro-Giene (Water Science)., copper fluoride, copper fluoride, cupric perchlorate, cupric perchlorate, copper chlorate, Tubercuprose., cupric tartrate, cupric phosphate, Cupric fluosilicate, cupric fluosilicate, copper sulfide, cuprous sulfide, cupric thiocyanate, Cuprous sulfocyanate, cupric tetramminosulfate, copper sulfate, copper chloride, Cu-lyt., copper citrate, copper metaborate, Copper hydrate, copper cyanider, the at least one of copper salicylate.
3. the preparation method of a kind of tumor thermotherapy according to claim 1 and magnetic resonance contrast agent multiprobe, is characterized in that described dispersant is at least one in stearmide, higher alcohol, vinyl bis-stearamides, glycerol monostearate, liquid paraffin, microcrystalline wax, barium stearate, chloroform, class of department 80, class 60 of department, Tween 80, tocopherol.
4. the preparation method of a kind of tumor thermotherapy according to claim 1 and magnetic resonance contrast agent multiprobe, it is characterized in that described surfactant is hyaluronic acid, cetyl trimethyl ammonium bromide, Dodecyl trimethyl ammonium chloride, DDA, sodium lauryl sulphate, dodecyl sodium sulfate, alevaire, dodecylbenzene sodium sulfonate, Triton X-100, polyoxyethylenesorbitan sorbitan monooleate, sorbitan monostearate, fatty acid distribution of coconut oil diglycollic amide, fatty alcohol-polyoxyethylene ether, at least one in polyoxyethylene lauryl ether.
5. the preparation method of a kind of tumor thermotherapy according to claim 1 and magnetic resonance contrast agent multiprobe, is characterized in that described alkali is at least one in potassium hydroxide, sodium hydroxide, ammonia, calcium hydroxide, barium hydroxide, Copper hydrate, magnesium hydroxide, ferrous hydroxide, hydrated ferric oxide., aluminium hydroxide.
6. the preparation method of a kind of tumor thermotherapy according to claim 1 and magnetic resonance contrast agent multiprobe, is characterized in that described magnetic compound is at least one in manganese dioxide, mangano-manganic oxide, manganese chloride, manganese sulfate, calcium chromate, manganess carbide, calcium acetate, potassium permanganate, Gadolinium trichloride, Digadolinium trisulfate, Gadolinia., ferroso-ferric oxide, oxygen ferrous iron, ferroso-ferric oxide, ferrum oxide, ferrous hydroxide, hydrated ferric oxide., ferrous sulfate and iron chloride.
7. the preparation method of a kind of tumor thermotherapy according to claim 1 and magnetic resonance contrast agent multiprobe, it is characterized in that described silicon source is silicon monoxide, trichlorosilane, white carbon, silicon disulfide, orthosilicic acid, Silicon fluoride., Silicon chloride., Silicon bromide., silicon tetraiodide, 1,1, at least one in 3,3-tetramethyl-disilazane, N-trimethyl silicon based imidazole, monosilane, Disilicoethane, Trisilicopropane, isobutyl silane, positive penta silane, ring penta silane, white carbon.
8. a kind of tumor thermotherapy according to any one of claim 1-7 and the preparation method of magnetic resonance contrast agent multiprobe, is characterized in that in above-mentioned steps b, and room temperature lower magnetic force mixing time is 4 ~ 6 hours.
9. a kind of tumor thermotherapy according to any one of claim 1-7 and the preparation method of magnetic resonance contrast agent multiprobe, is characterized in that in above-mentioned steps d, and twice heating-up temperature is 80 DEG C, and 300 ~ 350 DEG C, the magnetic agitation time is 20 ~ 40 minutes.
10. a kind of tumor thermotherapy according to any one of claim 1-7 and the preparation method of magnetic resonance contrast agent multiprobe, it is characterized in that in above-mentioned steps e, temperature is 40 ~ 60 DEG C, and the magnetic agitation time is 48 ~ 72 hours, and rotating evaporation temperature requires more than 40 ~ 50 DEG C.
The preparation method of 11. a kind of tumor thermotherapies according to any one of claim 1-7 and magnetic resonance contrast agent multiprobe, it is characterized in that in above-mentioned steps g, step h, temperature is 60 ~ 80 DEG C, and the magnetic agitation time is 1 ~ 2 hour, in step g ultrasonic 1 ~ 2 hour.
The preparation method of 12. a kind of tumor thermotherapies according to any one of claim 1-7 and magnetic resonance contrast agent multiprobe, it is characterized in that in above-mentioned steps i, temperature is more than 60 ~ 80 DEG C, and return time is 1 ~ 2 hour.
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| CN102961753A (en) * | 2012-12-06 | 2013-03-13 | 东华大学 | Copper sulfide/mesoporous silicon dioxide core-shell nano material as well as preparation method and application thereof |
| CN104043137A (en) * | 2014-05-28 | 2014-09-17 | 上海纳米技术及应用国家工程研究中心有限公司 | Intestinal-tract targeted magnetic resonance contrast agent based on mesoporous silica and preparation method thereof |
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| CN105056243B (en) * | 2015-07-22 | 2017-11-14 | 郑州大学 | A kind of pharmaceutical composition of the mesoporous copper sulfide of hyaluronic acid decorated magnetic hollow and preparation method and application |
| CN105906822A (en) * | 2016-04-29 | 2016-08-31 | 郑州大学 | Preparation method and application of polylactic acid-glycolic acid copolymer coated by manganese dioxide layer |
| CN109731147A (en) * | 2018-12-24 | 2019-05-10 | 西安交通大学 | Multi-functional PCS Hybrid nanofibers bio-medical method for producing elastomers and application |
| CN109731147B (en) * | 2018-12-24 | 2020-08-28 | 西安交通大学 | Preparation method and application of multifunctional PCS (Poly styrene-butadiene-styrene) hybrid nanofiber biomedical elastomer |
| CN110755407A (en) * | 2019-12-03 | 2020-02-07 | 长沙理工大学 | Manganese dioxide/glucose oxidase @ hyaluronic acid composite anti-cancer material and preparation and application thereof |
| CN114099674A (en) * | 2021-11-23 | 2022-03-01 | 中山大学 | Copper or zinc carrier carrying diethyl dithiocarbamate prodrug, preparation and application |
| CN114099674B (en) * | 2021-11-23 | 2023-07-04 | 中山大学 | Copper or zinc carrier for carrying diethyl dithiocarbamic acid prodrug and preparation and application thereof |
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