CN104491887B - A kind of preparation method of lympha targeted acoustic contrast agent - Google Patents
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Abstract
The present invention discloses a kind of preparation method of lympha targeted acoustic contrast agent, and surfactant is added in alkaline solution, stirs, until completely dissolved, silicon source is added in above-mentioned solution, continues to stir, collosol intermixture is subsequently generated, powdery product is arrived after washing centrifugation drying after stirring；Thing is produced to the powdered nano-porous materials for removing surfactant after high-temperature calcination；Powdered porous material is scattered in organic solvent, silane coupler is added, after stirring, powdery product is obtained with ethanol and water washing, and after centrifuging drying；Powder is scattered in deionized water, crosslinking agent and Sodium Hyaluronate is added, after stirring, is washed with water and centrifuges and dry to obtain nano particle；Particle is scattered in deionized water, fluorocarbons is added dropwise, stirs and uses ionized water washing and drying, produce lympha targeted acoustic contrast agent.The integration of lympha targeted function and ultrasonic contrast can be achieved in the present invention.
Description
Technical field
The present invention relates to the preparation field of nano material, more particularly to a kind of preparation side of lympha targeted acoustic contrast agent
Method.
Background technology
Modern medicine iconography is from traditional image anatomy, and progressively development enters functional imaging and molecular imaging
In the epoch, it is using ultrasound that traditional molecular image technology, which includes the ultrasound molecular iconographies such as MRI SPECT/PET optical imageries,
Imaging Method, is combined by targeted ultrasound contrast agent with internal ligands specific, and observation target tissue is thin in histocyte and Asia
The imaging of born of the same parents' level, is reached with this and reflects change (Lanza G M, Wickline S of the pathological tissues on molecular basis in body
A. Targeted ultrasonic contrast agents for molecular imaging and therapy[J].
Progress in cardiovascular diseases, 2001, 44(1): 13-31)..With engineering in medicine and calculating
The development of machine technology, Medical Imaging provides the medical image of multiple modalities for clinical diagnosis.The medical image of different modalities
The different information of the related internal organs of human body and tissue can be provided.Ultrasonic imaging can consistently, dynamically observe the motion of internal organs
And function；Limitation of the lesion rather than its imaging layering can be followed the trail of.But the resolution ratio and definition of Ultrasonic Diagnosis itself compared with
Low, gas is very big on ultrasound influence, therefore effect of the targeted ultrasound contrast in medical diagnosis on disease is increasingly taken seriously.Targeting is super
Sound contrast agent can be combined with internal ligands specific, can be targetted and be accumulated on specific target tissue cells by blood circulation,
So that destination organization obtained in ultrasonic image the preferable targeted ultrasound contrast agent of specific mark enhancing need to reach it is following
It is required that（Lanza G M, Wickline S A. Targeted ultrasonic contrast agents for
molecular imaging and therapy[J]. Progress in cardiovascular diseases, 2001,
44(1): 13-31.）:450~700nm of diameter, can flow through target area;Circulating half-life is long, and in the target area residence time
It is long;Selectivity can be carried out with the surface antigen determinant of region of interest and sensitiveness is combined;The combination of contrast agent and target position should
Firmly and be attached to the contrast agent on target position should be kept during ultrasonic examination stably;Consumption is few, preferably milligram level or more
It is few;Small toxicity;Current with the potentiality for carrying medicine or gene, targeted ultrasound contrast agent is typically by specific antibody
Or part is prepared with the mode that microbubble surface is combined, specific method has two kinds of electrostatic of Electrostatic Absorption method and covalent coupling method to inhale
Attached method utilizes the chemistry and charge characteristic of contrast agent shell in itself, by antibody or part absorption on microbubble contrast agent surface, but its
Should be that specific antibody or part are connected into microvesicle by covalent coupling method mode to make with reference to insecure reliable ideal style
Shadow agent surface.
The content of the invention
The object of the invention be directed to defect of the prior art, with the focus-fluorocarbons studied at present do basis there is provided
A kind of preparation method of lympha targeted acoustic contrast agent.
The method of the present invention comprises the following steps that number refers to mass fraction in following steps：
A, 20~40 parts of surfactant is added in 10~30 parts of alkaline solutions, at least 5 are stirred more than 30 DEG C
Minute, after surfactant is completely dissolved, 100~250 parts of silicon sources are added in the solution, continue to stir more than 30 DEG C
After at least 5 minutes, collosol intermixture is subsequently generated, at least six hour is then stirred more than 30 DEG C, with alcohol and deionized water
The centrifuge washing more than 5000 turns, then in an oven more than 60 DEG C dry at least 20 hours and obtain powdery product；
B, the powder for obtaining above-mentioned a are fired, and sintering temperature requirement is more than 500 DEG C, and the heat time is at least 4 small
When, that is, obtain removing the powdered nano-porous materials of surfactant；
C, 50~100 parts of the nano particle that above-mentioned b is obtained is scattered in 500~800 parts of organic solvent, adds 10
~20 parts of silane coupler, after being stirred more than 6 hours more than 30 DEG C, is distinguished water washing, and is used 5000 with ethanol, deionization
Centrifuged more than turning, then in an oven more than 60 DEG C dry at least 20 hours and obtain powdered nano-porous materials；
D, 100~200 parts of powdered nano-porous materials obtained by above-mentioned c are scattered in 800~900 parts of water,
The crosslinking agent and 50~60 parts of Sodium Hyaluronate of 10~20 parts of addition, after 30 DEG C are stirred more than 5 hours above and below, are washed with water
Wash, and more than 5000 turns centrifugations, then in an oven more than 60 DEG C dry at least 20 hours and obtain powdery product；
In e, 3000~4000 parts of water for being scattered in 500~600 parts of powdered nano particles obtained by above-mentioned d, delay
The slow fluorocarbons for being added dropwise 20~30 parts, is stirred more than 5 hours more than 30 DEG C, and is washed with water, more than 5000 turns centrifugations,
Then in an oven more than 60 DEG C dry at least 20 hours, obtain the nanometer of the acoustic contrast agent with lympha targeted function
Grain.
Preferably, described surfactant be cetyl trimethylammonium bromide, it is DTAB, double
Octadecyldimethyl ammonium bromide, lauryl sodium sulfate, dodecyl sodium sulfate, alevaire, neopelex,
Triton X-100, polyoxyethylene, sorbitan mono-oleic acid ester, sorbitan monostearate, fatty acid distribution of coconut oil two
At least one of glycollic amide, AEO, ethoxylated dodecyl alcohol.
Preferably, described alkaline solution be potassium hydroxide, sodium hydroxide, calcium hydroxide, barium hydroxide, Kocide SD,
At least one of magnesium hydroxide, ferrous hydroxide, iron hydroxide, aluminium hydroxide, sodium carbonate liquor and ammoniacal liquor.
Preferably, described silicon source be silicon monoxide, trichlorosilane, white carbon, silicon disulfide, orthosilicic acid, ocratation,
Silicon tetrachloride, silicon bromide, silicon tetraiodide, 1,1,3,3- tetramethyl-disilazanes, N- trimethyl silicon based imidazoles, monosilane, second
At least one of silane, trisilalkane, isobutyl silane, positive penta silane, the silane of ring penta, white carbon.
Preferably, described organic solvent is benzene,toluene,xylene, pentane, hexane, octane, hexamethylene, cyclohexanone, first
Phenylcyclohexanone, chlorobenzene, dichloro-benzenes, dichloromethane, methanol, ethanol, isopropanol, ether, expoxy propane, methyl acetate, acetic acid second
Ester, propyl acetate, acetone, espeleton, methylisobutylketone, glycol monoethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether,
At least one of acetonitrile, pyridine, phenol.
Preferably, described porous material is diatomite, zeolite, activated carbon, Woelm Alumina, micropore glass, porous pottery
At least one of porcelain, floating bead, mesoporous silicon oxide, zirconium oxide, titanium dioxide, aluminum oxide, mesoporous lithium vanadate.
Preferably, described silane coupler is vinyl trichlorosilane, VTES, vinyl three
(beta-methoxy ethyoxyl) silane, γ-glycidylpropyl-trimethoxy silane, γ-methacryloxypropyl-trimethoxy
Base silane, N- (β-aminoethyl)-γ-aminopropyl-trimethoxy silane, N- (β-aminoethyl)-γ-aminopropyl-methyl-trimethoxy
At least one of base silane, γ-chloropropyl-trimethoxy silane.
Preferably, described crosslinking agent is tetraisocyanate, propane diamine, polyethylene glycol, polypropylene glycol, trihydroxy methyl third
Alkane, polypropylene glycol glycidol ether, a- methyl styrenes, acrylonitrile, acrylic acid, methacrylic acid, glyoxal, positive silicic acid second
Ester, methyl silicate, trimethoxy silane, p-methyl benzenesulfonic acid, paratoluensulfonyl chloride, diacrylate-BDO ester, diformazan
Base acrylic acid glycol ester, butyl acrylate, cumyl peroxide, peroxidating double 2,4 one dichloro-benzoyls, acrylic acid, third
Olefin(e) acid hydroxyl ethyl ester, hydroxypropyl acrylate, methacrylic acid, hydroxyethyl methacrylate, hydroxy propyl methacrylate, divinyl
At least one of benzene, N hydroxymethyl acrylamide, DAAM.
Preferably, described fluorocarbons is perfluoro butyl sulfonic acid fluoride (FC-4), full-fluorine octyl sulfuryl fluoride (FC-8), fluorine
Worm amine (FC-9), N- ethylperfluoro octyl group sulfonamide ethanol (FC-10), perfluoro octyl sulfonic acid potassium (FC-95), perfluoro butyl sulfonic acid
Potassium (FC-98), perfluorinated octyl sulfuryl amine (FC-99), perfluoro octyl sulfonic acid ammonium (FC-120), perfluoro capryl quaternary ammonium iodide (FC-
134), perfluoro octyl sulfonic acid tetraethyl amine (FC-248), N- perfluoroalkyl group sulfonyls, propyl-triethoxysilicane (FC-922),
Perfluor alkane (FC-40), perfluoroalkyl acrylate (FC-14), N- fluorobenzenesulfonimides, perfluoro hexyl sulfuryl fluoride, perflexane
In potassium sulfonate, N- methyl perfluoro hexyls sulfonamide, N- methyl perfluoro hexyl sulfoamidos ethanol, perfluorodecalin, perfluamine
At least one.
Preferably, in above-mentioned steps a, 20~40 parts of surfactant is added in 10~30 parts of alkaline solutions,
Stirred 5~10 minutes at 30~50 DEG C, after surfactant is completely dissolved, 100~250 parts of silicon sources are added to the solution
In, continue after being stirred 10~15 minutes at 30~50 DEG C, subsequently generate collosol intermixture, then stir 6 at 30~50 DEG C
~9 hours, with alcohol and deionized water in 6000 ~ 8000 turns of centrifuge washings, then in an oven with 60~80 DEG C of drying 20
Obtain powdery product within~30 hours.
Preferably, in above-mentioned steps b, it is calcined 4~6 hours at 500~550 DEG C.
Preferably, in above-mentioned steps c：Using magnetic agitation, after 30~40 DEG C are stirred 6~8 hours, three are washed with ethanol
After, twice of washing is washed with deionized, and the heart is left with 6000~8000, then in an oven with 70~80 DEG C of drying 20
Obtain powdery product within~30 hours.
Preferably, in above-mentioned steps d, using magnetic agitation, after being stirred 7~9 hours at 30~50 DEG C, it is washed with water,
And 7000~8000 leave the heart, then powdery product is obtained within 20~40 hours with 70~80 DEG C of drying in an oven.
Preferably, in above-mentioned steps e, using magnetic agitation, stir 8~10 hours, and be washed with water at 30~40 DEG C,
6000~8000 leave the heart, then obtain lympha targeted acoustic contrast agent within 20~30 hours with 60~80 DEG C of drying in an oven
Nano particle.
The above method of the present invention forms porous material structure by adding surfactant, alkali, silicon source, then connects targeting greatly
Molecule, by fluorocarbons absorption in duct, being formed has lympha targeted acoustic contrast agent.The preparation method is simple, gained
Product stability it is good, the demand of clinical practice can be met.
Compared with prior art, the present invention has following beneficial effect：
The advantage of the invention is that technology preparation method is simple, the product loose structure stability of gained is good, bio-compatible
Property it is good, easily metabolism, it is possible to achieve lympha targeted ultrasonic contrast.
A kind of lympha targeted acoustic contrast agent of the present invention, is applied in clinical diagnostic process, it is possible to achieve lympha targeted
Ultrasonic contrast, the advantage for targeting of taking the initiative is accurately positioned lesions position, thus just can obtain more complete pathological information,
The diagnostic accuracy and diagnosis efficiency of disease is greatly improved, the demand of many clinical practices is disclosure satisfy that.
Embodiment
With reference to specific embodiment, the present invention is described in detail.Following examples will be helpful to the technology of this area
Personnel further understand the present invention, but the invention is not limited in any way.It should be pointed out that to the ordinary skill of this area
For personnel, without departing from the inventive concept of the premise, various modifications and improvements can be made.These belong to the present invention
Protection domain.
Embodiment 1；
A, mass fraction is added in 10 parts of alkaline solutions for 20 parts of surfactant, stirred 5 minutes at 30 DEG C,
After surfactant is completely dissolved, 100 parts of silicon sources are added in the solution, continued after being stirred 5 minutes at 30 DEG C, then
Collosol intermixture is generated, 6 hours are then stirred at 30 DEG C, with alcohol and deionized water in 5000 turns of centrifuge washings, then
In an oven powdery product is obtained with 60 DEG C of drying within 20 hours；
B, the powder for obtaining above-mentioned a obtain removing the powder of surfactant after being calcined 4 hours at 500 DEG C
The nano-porous materials of last shape；
C, the mass fraction for obtaining above-mentioned b are scattered in 500 parts of organic solvent for 50 parts of nano particle, add 10
The silane coupler of part, after 30 DEG C are stirred 6 hours, is washed with ethanol and is washed with deionized after three times twice, and use 6000
The heart is left, then powdery product is obtained within 20 hours with 60 DEG C of drying in an oven；
D, the mass fraction obtained by above-mentioned c is scattered in 800 parts of water for 100 parts of powdered nano particle, added
10 parts of crosslinking agent and 50 parts of Sodium Hyaluronate, after being stirred 7 hours at 40 DEG C, are washed with water, and leave the heart with 7000, with
Obtain powdery product within 20 hours with 60 DEG C of drying in an oven afterwards；
In e, 3000 parts of water for being scattered in the mass fraction obtained by above-mentioned d for 500 parts of powdered nano particles, slowly
20 parts of fluorocarbons is added dropwise, is stirred 5 hours at 30 DEG C, and is washed with water, 5000 leave the heart, then in an oven with 60
DEG C drying obtains the nano particle with lympha targeted acoustic contrast agent in 20 hours.
Embodiment 2；
A, mass fraction is added in 15 parts of alkaline solutions for 25 parts of surfactant, stirred 8 minutes at 30 DEG C,
After surfactant is completely dissolved, 150 parts of silicon sources are added in the solution, continued after being stirred 10 minutes at 30 DEG C, with
After generate collosol intermixture, 7 hours are then stirred at 40 DEG C, with alcohol and deionized water in 6500 turns of centrifuge washings, with
Obtain powdery product within 24 hours with 65 DEG C of drying in an oven afterwards；
B, the powder for obtaining above-mentioned a obtain removing the powder of surfactant after being calcined 6 hours at 550 DEG C
The nano-porous materials of shape；
C, the mass fraction for obtaining above-mentioned b are scattered in 700 parts of organic solvent for 60 parts of nano particle, add 20
The silane coupler of part, after 30 DEG C are stirred 7 hours, is washed with ethanol and is washed with deionized after three times twice, and use 6500
The heart is left, then powdery product is obtained within 25 hours with 75 DEG C of drying in an oven；
D, the mass fraction obtained by above-mentioned c is scattered in 850 parts of water for 100 parts of powdered nano particle, added
15 parts of crosslinking agent and 55 parts of Sodium Hyaluronate, after being stirred 8 hours at 45 DEG C, are washed with water, and 5000 leave the heart, then
In an oven powdery product is obtained with 70 DEG C of drying within 20 hours；
In e, 3000 parts of water for being scattered in the mass fraction obtained by above-mentioned d for 500 parts of powdered nano particles, slowly
20~30 parts of fluorocarbons is added dropwise, is stirred 8~10 hours at 30~40 DEG C, and is washed with water, 6000~8000 leave
The heart, then obtains the nanometer with lympha targeted acoustic contrast agent in 20~30 hours with 60~80 DEG C of drying in an oven
Grain.
Embodiment 3：
A, mass fraction is added in 20 parts of alkaline solutions for 25 parts of surfactant, 10 points are stirred at 40 DEG C
Clock, after surfactant is completely dissolved, 200 parts of silicon sources are added in the solution, are continued after being stirred 15 minutes at 40 DEG C,
Collosol intermixture is subsequently generated, 6 hours are then stirred at 40 DEG C, with alcohol and deionized water in 6000 turns of centrifuge washings,
Then obtain powdery product within 20 hours with 80 DEG C of drying in an oven；
B, the powder for obtaining above-mentioned a obtain removing the powder of surfactant after being calcined 6 hours at 550 DEG C
The nano-porous materials of shape；
C, the mass fraction for obtaining above-mentioned b are scattered in 500 parts of organic solvent for 100 parts of nano particle, are added
20 parts of silane coupler, after 30 DEG C are stirred 6 hours, is washed with ethanol and is washed with deionized after three times twice, is used in combination
6000 leave the heart, then obtain powdery product within 30 hours with 70 DEG C of drying in an oven；
D, the mass fraction obtained by above-mentioned c is scattered in 800 parts of water for 100 parts of powdered nano particle, added
10 parts of crosslinking agent and 50 parts of Sodium Hyaluronate, after being stirred 7 hours at 40 DEG C, are washed with water, and leave the heart with 7000, with
Obtain powdery product within 25 hours with 60 DEG C of drying in an oven afterwards；
In e, 4000 parts of water for being scattered in the mass fraction obtained by above-mentioned d for 550 parts of powdered nano particles, slowly
20 parts of fluorocarbons is added dropwise, is stirred 8 hours at 30 DEG C, and is washed with deionized, 6000 leave the heart, then in baking oven
It is middle to obtain the nano particle with lympha targeted acoustic contrast agent within 30 hours with 60 DEG C of drying.
Embodiment 4：
A, mass fraction is added in 30 parts of alkaline solutions for 30 parts of surfactant, 10 points are stirred at 30 DEG C
Clock, after surfactant is completely dissolved, 180 parts of silicon sources are added in the solution, are continued after being stirred 15 minutes at 40 DEG C,
Collosol intermixture is subsequently generated, 6 hours are then stirred at 40 DEG C, with alcohol and deionized water in 6000 turns of centrifuge washings,
Then obtain powdery product within 20 hours with 60 DEG C of drying in an oven；
B, the powder for obtaining above-mentioned a obtain removing the powder of surfactant after being calcined 6 hours at 525 DEG C
The nano-porous materials of shape；
C, the mass fraction for obtaining above-mentioned b are scattered in 700 parts of organic solvent for 55 parts of nano particle, add 20
The silane coupler of part, after 30 DEG C are stirred 6 hours, is washed with ethanol and is washed with deionized after three times twice, and use 7000
The heart is left, then powdery product is obtained within 20 hours with 80 DEG C of drying in an oven；
D, the mass fraction obtained by above-mentioned c is scattered in 800 parts of water for 150 parts of powdered nano particle, added
20 parts of crosslinking agent and 50 parts of Sodium Hyaluronate, after being stirred 7 hours at 40 DEG C, are washed with water, and leave the heart with 7000, with
Obtain powdery product within 20 hours with 70 DEG C of drying in an oven afterwards；
In e, 3700 parts of water for being scattered in the mass fraction obtained by above-mentioned d for 550 parts of powdered nano particles, slowly
20 parts of fluorocarbons is added dropwise, is stirred 8 hours at 35 DEG C, and is washed with water, 6000 leave the heart, then in an oven with 60
DEG C drying obtains the nano particle with lympha targeted acoustic contrast agent in 25 hours.
Embodiment 5：
A, 40 parts of surfactant is added in 30 parts of alkaline solutions, stirred 5 minutes at 30 DEG C, treat surfactant
After being completely dissolved, 250 parts of silicon sources are added in the solution, continued after 30 DEG C are stirred 5 minutes, colloidal sol mixing is subsequently generated
Thing, then stirs 6 hours, with alcohol and deionized water in 5000 turns of centrifuge washings, then in an oven with 60 DEG C at 30 DEG C
Drying obtains powdery product in 20 hours；
B, the powder for obtaining above-mentioned a are fired, and sintering temperature requirement is 500 DEG C, and the heat time is 4 hours, that is, is obtained
Remove the powdered nano-porous materials of surfactant；
C, the mass fraction for obtaining above-mentioned b are scattered in 800 parts of organic solvent for 100 parts of nano particle, are added
20 parts of silane coupler, after 30 DEG C are stirred 6 hours, is washed with ethanol and is washed with deionized after three times twice, is used in combination
5000 leave the heart, then obtain powdery product within 20 hours with 60 DEG C of drying in an oven；
D, the mass fraction obtained by above-mentioned c is scattered in 900 parts of water for 200 parts of powdered nano particle, added
20 parts of crosslinking agent and 60 parts of Sodium Hyaluronate, after being stirred 5 hours at 30 DEG C, are washed with water, and 5000 leave the heart, then
In an oven powdery product is obtained with 60 DEG C of drying within 20 hours；
In e, 4000 parts of water for being scattered in the mass fraction obtained by above-mentioned d for 600 parts of powdered nano particles, slowly
30 parts of fluorocarbons is added dropwise, is stirred 5 hours at 30 DEG C, and is washed with water, 5000 leave the heart, then in an oven with 60 DEG C
Drying obtains the nano particle with lympha targeted acoustic contrast agent in 20 hours.
The specific embodiment of the present invention is described above.It is to be appreciated that the invention is not limited in above-mentioned
Particular implementation, those skilled in the art can make various deformations or amendments within the scope of the claims, this not shadow
Ring the substantive content of the present invention.
Claims (2)
1. a kind of preparation method of lympha targeted acoustic contrast agent, it is characterised in that this method comprises the following steps, following steps
Middle number refers to mass fraction：
A, 20~40 parts of surfactant is added in 10~30 parts of alkaline solutions, stirred more than 30 DEG C at least 5 minutes,
After surfactant is completely dissolved, 100~250 parts of silicon sources are added in the solution, continuation stirs at least 5 more than 30 DEG C
After minute, collosol intermixture is subsequently generated, at least six hour is then stirred more than 30 DEG C, is existed with alcohol and deionized water
More than 5000 turns centrifuge washings, then in an oven more than 60 DEG C dry at least 20 hours and obtain powdery product；
B, the powder for obtaining above-mentioned a are fired, and sintering temperature requirement is more than 500 DEG C, and the heat time is at least 4 hours, i.e.,
Obtain removing the powdered nano-porous materials of surfactant；
C, 50~100 parts of the nano particle that above-mentioned b is obtained is scattered in 500~800 parts of organic solvent, adds 10~20
Part silane coupler, more than 30 DEG C stir more than 6 hours after, washed respectively with ethanol, deionized water, and with 5000 turns with
Upper centrifugation, then in an oven more than 60 DEG C dry at least 20 hours and obtain powdered nano-porous materials；
D, 100~200 parts of powdered nano-porous materials obtained by above-mentioned c are dissipated in 800~900 parts of water, add 10
~20 parts of crosslinking agent and 50~60 parts of Sodium Hyaluronate, after 30 DEG C are stirred more than 5 hours above and below, are washed with water, and
More than 5000 turns centrifugations, then in an oven more than 60 DEG C dry at least 20 hours and obtain powdery product；
In e, 3000~4000 parts of water for being scattered in 500~600 parts of powdered nano-porous materials obtained by above-mentioned d, delay
The slow fluorocarbons for being added dropwise 20~30 parts, is stirred more than 5 hours more than 30 DEG C, and is washed with water, more than 5000 turns centrifugations,
Then in an oven more than 60 DEG C dry at least 20 hours, obtain the nano particle of lympha targeted acoustic contrast agent；
Described surfactant is lauryl sodium sulfate, dodecyl sodium sulfate, alevaire, DBSA
Sodium, Triton X-100, polyoxyethylene, sorbitan mono-oleic acid ester, sorbitan monostearate, fatty acid distribution of coconut oil
At least one of diglycollic amide, AEO, ethoxylated dodecyl alcohol；
Described alkaline solution is potassium hydroxide, sodium hydroxide, calcium hydroxide, barium hydroxide, Kocide SD, magnesium hydroxide, hydrogen
At least one of ferrous oxide, iron hydroxide, aluminium hydroxide, sodium carbonate liquor and ammoniacal liquor；
Described silicon source is silicon monoxide, trichlorosilane, white carbon, silicon disulfide, orthosilicic acid, ocratation, silicon tetrachloride, four
Silicon bromide, silicon tetraiodide, 1,1,3,3- tetramethyl-disilazanes, N- trimethyl silicon based imidazoles, monosilane, disilane, trisilalkane,
At least one of isobutyl silane, positive penta silane, the silane of ring penta；
Described organic solvent is benzene,toluene,xylene, pentane, hexane, octane, hexamethylene, cyclohexanone, toluene cyclohexanone, chlorine
Benzene, dichloro-benzenes, dichloromethane, methanol, ethanol, isopropanol, ether, expoxy propane, methyl acetate, ethyl acetate, propyl acetate,
Acetone, espeleton, methylisobutylketone, glycol monoethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, acetonitrile, pyridine, benzene
At least one of phenol；
Described silane coupler is vinyl trichlorosilane, VTES, (the beta-methoxy ethoxy of vinyl three
Base) silane, γ-glycidylpropyl-trimethoxy silane, γ-methacryloxypropyl-trimethoxy silane, N- (β-
Aminoethyl)-γ-aminopropyl-trimethoxy silane, N- (β-aminoethyl)-γ-aminopropyl-Methyl-trimethoxy silane, γ-chlorine
At least one of propyl-trimethoxysilane；
Described crosslinking agent is tetraisocyanate, propane diamine, polyethylene glycol, polypropylene glycol, trimethylolpropane, polypropylene glycol contracting
Water glycerin ether, a- methyl styrenes, acrylonitrile, glyoxal, tetraethyl orthosilicate, methyl silicate, trimethoxy silane, to toluene
Sulfonic acid, paratoluensulfonyl chloride, diacrylate-BDO ester, GDMA, butyl acrylate, peroxide
Change diisopropylbenzene (DIPB), peroxidating double 2,4 one dichloro-benzoyls, acrylic acid, hydroxy-ethyl acrylate, hydroxypropyl acrylate, metering systems
Acid, hydroxyethyl methacrylate, hydroxy propyl methacrylate, divinylbenzene, N hydroxymethyl acrylamide, diacetone acrylamide acyl
At least one of amine；
Described fluorocarbons be perfluoro butyl sulfonic acid fluoride (FC-4), full-fluorine octyl sulfuryl fluoride (FC-8), sulfluramid (FC-9),
N- ethylperfluoro octyl group sulfonamide ethanol (FC-10), perfluoro octyl sulfonic acid potassium (FC-95), perfluorobutyl potassium sulfonate (FC-98),
Perfluorinated octyl sulfuryl amine (FC-99), perfluoro octyl sulfonic acid ammonium (FC-120), perfluoro capryl quaternary ammonium iodide (FC-134), perfluor
Octyl sulfonic acid tetraethyl amine (FC-248), N- perfluoroalkyl group sulfonyls, propyl-triethoxysilicane (FC-922), perfluor alkane (FC-
40), perfluoroalkyl acrylate (FC-14), N- fluorobenzenesulfonimides, perfluoro hexyl sulfuryl fluoride, perfluorohexanesulfonic acid potassium, N- first
At least one of base perfluoro hexyl sulfonamide, N- methyl perfluoro hexyl sulfoamidos ethanol, perfluorodecalin, perfluamine.
2. a kind of preparation method of lympha targeted acoustic contrast agent according to claim 1, it is characterised in that above-mentioned steps a
In, 20~40 parts of surfactant is added in 10~30 parts of alkaline solutions, stirred 5~10 minutes at 30~50 DEG C,
After surfactant is completely dissolved, 100~250 parts of silicon sources are added in the solution, continuation stirs 10 at 30~50 DEG C
After~15 minutes, collosol intermixture is subsequently generated, 6~9 hours are then stirred at 30~50 DEG C, with alcohol and deionized water
In 6000 ~ 8000 turns of centrifuge washings, then powdery product is obtained within 20~30 hours with 60~80 DEG C of drying in an oven.
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