CN105920625B - A kind of preparation method for the diagnosis and treatment preparation integrating ultrasonic contrast and thermotherapy - Google Patents
A kind of preparation method for the diagnosis and treatment preparation integrating ultrasonic contrast and thermotherapy Download PDFInfo
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- ZJIJAJXFLBMLCK-UHFFFAOYSA-N perfluorohexane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F ZJIJAJXFLBMLCK-UHFFFAOYSA-N 0.000 description 1
- NJCBUSHGCBERSK-UHFFFAOYSA-N perfluoropentane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F NJCBUSHGCBERSK-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/221—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by the targeting agent or modifying agent linked to the acoustically-active agent
-
- 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
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
- A61K49/223—Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5115—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
Abstract
A kind of preparation method for the diagnosis and treatment preparation integrating ultrasonic contrast and thermotherapy, the steps include: that 1) 1-50mg organic-inorganic complex lipid and 0.1-10mg polyethylene glycol are dissolved in 0.1-1mL dehydrated alcohol；2) 1-25mg menthol is dissolved in 1-20mL ultrapure water, heating water bath is mixed to 45 DEG C, then with the aqueous solution of 1-10mL indocyanine green；3) ethanol solution of organic-inorganic complex lipid and polyethylene glycol obtained in step 1) is rapidly injected in the mixed liquor that step 2 obtains under conditions of water bath sonicator；4) after Probe Ultrasonic Searching, obtain to inner cavity contain indocyanine green and menthol and surface be covered with nanometer grade thickness and good biocompatibility inorganic silicate shell organic-inorganic complex lipid nano particle.Complex lipid diagnosis and treatment preparation of the invention, which can be realized, carries out photo-thermal therapy to tumor tissues under ultrasonic visualization observation, and stability is good, and to human body without obvious toxic-side effects, preparation method is simple, and equipment requirement is lower.
Description
Technical field
The present invention relates to field of biomedical materials, are specifically related to a kind of diagnosis and treatment for integrating ultrasonic contrast and thermotherapy
The preparation method of preparation.
Background technique
Cancer is a kind of disease with height heterogeneity and extremely strong adaptability, is needed according to the characteristics of patient and disease
Progress selects different types of diagnose and treat scheme.One kind is by the nanometer diagnosis and treatment preparation of Clinics and Practices function integration swollen
Tumor therapy field is gradually risen.Nanometer formulation is combined when diagnosis and treatment can provide the diagnoses and treatment scheme of various personalizations for patient, from
And improve therapeutic effect.Therefore, research and development novel multifunctional nano diagnosis and treatment preparation has great importance, and ultrasonic imaging is to face at present
Widely applied diagnostic method on bed.
Acoustic contrast agent is a kind of diagnostic preparation that can significantly increase ultrasound detection signal, and main component is micro- gas
Bubble.Backscatter signals can be enhanced in acoustic contrast agent, to greatly improve ultrasonic diagnosis effect.Currently, domestic clinically use
To acoustic contrast agent be sound Novi (SonoVue), it is by the microvesicle that is formed of phosphatide package SF6 gas, and partial size is 2~8 μ
m.Although obtaining successful application to varying degrees, still using SonoVue as the micron order acoustic contrast agent of representative
There are many problems: being on the one hand that partial size is big, therefore is limited only to blood pool imaging, is not easy to realize and examine disease outside its blood vessel
Disconnected and treatment；It on the other hand is that sound Novi is since coated fertilizer is lipid, and lipid in nature is not sufficiently stable, in vivo the duration
Fall short of, the radiography duration is short, so will using microbubble contrast agent realize tumour molecular imaging there is also certain difficulties.
Therefore, the strong acoustic contrast of searching miniaturization, penetration power becomes the research direction important for ultrasonic image field, also becomes and faces
Bed diagnosis and disease treatment there is an urgent need to.Nanoscale ultrasound contrast agents have than commercial small ten times of microbubble contrast agent or so
The potentiality diagnosed outside blood vessel.Its partial size is small, can realize and develop outside blood vessel by blood vessel endothelium system.Although nanoscale is ultrasonic
Contrast agent can be realized to develop outside blood vessel, but is simply possible to use in the early diagnosis of cancer.
Currently, the liquid fluorocarbon class ultrasonic contrast that research is more, such as perflexane, perflenapent, perfluorinated butane, liquid
It is that the mode of overbunching realizes that ultrasonic development enhances that core classes contrast agent, which mainly leads to, but this mode cannot reach preferable ultrasound
Development effect.Therefore, researcher develops a kind of Solid core class contrast agent --- menthol.Menthol is a kind of energy production
Raw typical mint flavored natural ring monoterpenoid compounds, exist, also referred to as menthol with free and ester state.Have only
Itch, relieve pain, anti-corrosion, stimulation, anesthesia, the pharmacy application such as refrigerant, anti-inflammatory and antibacterial agent, can be used for treating headache, neuralgia, itch
And respiratory inflammation, atrophic rhinitis, celostomia etc..It is commonly used for the additive of cigarette, toothpaste, perfume, beverage and candy.Menthol
Strong volatility it is extremely strong, menthol gas microbubbles can be generated in its natural state, play enhancing ultrasonic contrast effect.By big
Amount shows well it is demonstrated experimentally that being sustained using menthol as the acoustic contrast agent of core with it, contains rate height, and ultrasonic effect is good and super
Sound duration long feature and be expected to become next-generation clinical ultrasound contrast agent.Select fusing point lower, and easily big in the liquid state
Amount volatilization generates the solid state class acoustic contrast agent of gaseous microbubble by being injected intravenously after body, it can be achieved that tumor tissues ultrasound is aobvious
Shadow.
In recent years, photo-thermal therapy (Photothermal therapy) is as a kind of method that oncotherapy is emerging, because of tool
There are positioning treatment, Micro trauma, has been increasingly becoming the research hotspot in the field.Photo-thermal therapy will dependent on photothermal conversion agent
Near infrared light (NIR) can be converted to thermal energy, and using normal tissue and tumour cell to the difference of temperature tolerance, reaching can
The therapeutic purposes for making apoptosis of tumor cells, not damaging normal tissue again.Photo-thermal therapy has become after operation, radiotherapy, chemotherapy and exempts from
Another new therapy after epidemic disease therapy is a kind of new effective means for treating tumour.Currently, common photothermal conversion agent packet
The materials such as gold nanorods, nanometer golden shell, indocyanine green, polypyrrole, graphene, carbon nanotube are included, wherein indocyanine green is unique
A kind of reagent for being imaged and diagnosing for physianthropy ratified by U.S. Food and Drug Administration (FDA), brilliant
The advantages such as photothermal conversion efficiency and good safety are studied extensively by people and are applied to biomedical diagnostic and therapy field.
But the easily aggregation rapidly in polar solvent of free indocyanine green, stability is poor, it is easily quickly removed in blood plasma,
Circulation time is short in vivo, these defects greatly limit the application of indocyanine green.
Summary of the invention
It is an object of the invention to there are problem and shortage for above-mentioned, one kind is provided and contains indocyanine green and menthol,
And the preparation method of the good organic-inorganic complex lipid diagnosis and treatment preparation for integrating ultrasonic contrast and thermotherapy of stability.
The technical scheme of the present invention is realized as follows:
The preparation method of the diagnosis and treatment preparation of the present invention for integrating ultrasonic contrast and thermotherapy, its main feature is that include with
Lower step:
1) 1-50mg organic-inorganic complex lipid and 0.1-10mg polyethylene glycol are dissolved in 0.1-1mL dehydrated alcohol；
2) 1-25mg menthol is dissolved in 1-20mL ultrapure water, heating water bath to 45 DEG C, then with 1-10mL indocyanine green
Aqueous solution mixing；
3) by the ethanol solution of organic-inorganic complex lipid and polyethylene glycol obtained in step 1) in water bath sonicator
Under the conditions of be rapidly injected in the mixed liquor that step 2 obtains；
4) it after Probe Ultrasonic Searching, obtains and has contained indocyanine green and menthol to inner cavity and surface is covered with nanometer grade thickness and life
The organic-inorganic complex lipid nano particle of the good inorganic silicate shell of object compatibility.
Wherein, the structure of organic inorganic compounding lipid in the step 1) both can be with are as follows:
；
Or:
。
Organic inorganic compounding lipid is to connect two hydrophobic carbon chains and a hydrophilic organosilicon by a molecule
The novel lipid molecule of alkane molecular composition, this molecule can form lipoid by sol-gel and self assembling process in water
Plastid has contained menthol droplet and indocyanine green solution to realize in the inner cavity of lipoid plastid, covers on its surface
There is the inorganic silicate shell of the good biocompatibility of nanometer grade thickness.
Ultrasonic time in the step 4) is 0.5-5min, ultrasonic power 30W, and the 3s that works stops 3s.
Compared with prior art, the present invention having the effect that
(1) complex lipid diagnosis and treatment preparation of the invention can not only reach tumor locus and angiography, and can be in radiography
While tumor by local is heated, achieve the effect that thermotherapy kills tumour cell and tissue, to realize in ultrasonic visible
Change the purpose that under observation tumor tissues are carried out with photo-thermal therapy；
(2) contrasting effects of complex lipid diagnosis and treatment preparation of the invention are persistently grown, and are received since nano grain surface is covered with
The inorganic silicate shell of meter level thickness, so siloxane network significantly increases compared with traditional lipid ultrasonic contrast agent
The stability of complex lipid can be in mild mode continuously since menthol has three phase transition of solid-liquid-vapour
Gas microbubbles and unconventional fierce phase transition are generated, to extend the blood circulation of complex lipid diagnosis and treatment preparation in vivo
Time provides more times for diagnosis；
(3) complex lipid diagnosis and treatment preparation of the invention has excellent biocompatibility and degradability, raw materials used Yin
Green, menthol of diindyl cyanines etc. is to human body without obvious toxic-side effects, and preparation method is simple, and equipment requirement is lower.
The present invention will be further described below with reference to the drawings.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of diagnosis and treatment preparation of the present invention.
Fig. 2 is the dynamic light scattering grain size distribution of diagnosis and treatment preparation of the present invention.
Fig. 3 is the transmission electron microscope picture of diagnosis and treatment preparation of the present invention.
Fig. 4 is that diagnosis and treatment preparation of the present invention stability result interior for 24 hours detects figure.
Fig. 5 is diagnosis and treatment preparation of the present invention and the luminosity that free indocyanine green measures in ultraviolet-visible spectrophotometric instrument
It is worth schematic diagram.
Fig. 6 is the photothermal conversion experimental result schematic diagram of diagnosis and treatment preparation of the present invention.
Fig. 7 is that external supersonic of the diagnosis and treatment preparation of the present invention after 808nm laser irradiation 5min images picture.
Fig. 8 is that the external continual ultrasonic of diagnosis and treatment preparation of the present invention images picture.
Specific embodiment
Embodiment 1:
It weighs 1mg organic-inorganic complex lipid and 0.1mg polyethylene glycol (DSPE-PEG2000) injects the anhydrous second of 0.1mL
Disperse in alcohol.1mg menthol powder is taken to be added in the serum bottle for filling 1mL ultrapure water, then heating water bath adds again to 45 DEG C
Enter the aqueous solution that 1mL concentration is 1mg/mL indocyanine green.It is under the conditions of water bath sonicator, organic-inorganic obtained above is compound
The ethanol solution of lipid and polyethylene glycol be rapidly injected indocyanine green, peppermint alcohol and water mixed liquor in, obtain pre-emulsion.It will
The Probe Ultrasonic Searching 0.5min(setting ultrasonic power of pre-emulsion ultrasonic cell disintegration instrument is 30w, and work 3s, stops 3s) after, it obtains
Contain the silicone grease matter nanoemulsions of indocyanine green and menthol.Finally dialysis removes free indocyanine green and contains to get inner cavity
There are indocyanine green and menthol and surface to be covered with having for the inorganic silicate shell of nanometer grade thickness and good biocompatibility
Machine-inorganic compounding lipidic nanoparticles.The structure of the complex lipid nano particle is as shown in Figure 1.
Embodiment 2:
It weighs 50mg organic-inorganic complex lipid and 10mg polyethylene glycol (DSPE-PEG2000) injects 1mL dehydrated alcohol
Middle dispersion.25mg menthol powder is taken to be added in the serum bottle for filling 20mL ultrapure water, then heating water bath adds again to 45 DEG C
Enter the aqueous solution that 10mL concentration is 1mg/mL indocyanine green.Under the conditions of water bath sonicator, organic-inorganic obtained above is answered
Close lipid and polyethylene glycol ethanol solution be rapidly injected indocyanine green, peppermint alcohol and water mixed liquor in, obtain pre-emulsion.
It is 30w by the Probe Ultrasonic Searching 5min(setting ultrasonic power of pre-emulsion ultrasonic cell disintegration instrument, work 3s, stops 3s) after, it obtains
Contain the silicone grease matter nanoemulsions of indocyanine green and menthol.Finally dialysis removes free indocyanine green and contains to get inner cavity
There are indocyanine green and menthol and surface to be covered with having for the inorganic silicate shell of nanometer grade thickness and good biocompatibility
Machine-inorganic compounding lipidic nanoparticles.The structure of the complex lipid nano particle is as shown in Figure 1.
Embodiment 3:
It weighs 25mg organic-inorganic complex lipid and 5mg polyethylene glycol (DSPE-PEG2000) injects 5mL dehydrated alcohol
Middle dispersion.12mg menthol powder is taken to be added in the serum bottle for filling 10mL ultrapure water, then heating water bath adds again to 45 DEG C
Enter the aqueous solution that 5mL concentration is 1mg/mL indocyanine green.It is under the conditions of water bath sonicator, organic-inorganic obtained above is compound
The ethanol solution of lipid and polyethylene glycol be rapidly injected indocyanine green, peppermint alcohol and water mixed liquor in, obtain pre-emulsion.It will
The Probe Ultrasonic Searching 2min(setting ultrasonic power of pre-emulsion ultrasonic cell disintegration instrument is 30w, and work 3s, stops 3s) after, it is wrapped
Carry the silicone grease matter nanoemulsions of indocyanine green and menthol.Finally dialysis removes free indocyanine green and has contained to get inner cavity
Indocyanine green and menthol and surface be covered with the inorganic silicate shell of nanometer grade thickness and good biocompatibility it is organic-
Inorganic compounding lipidic nanoparticles.The structure of the complex lipid nano particle is as shown in Figure 1.
Embodiment 4:
It weighs 5mg organic-inorganic complex lipid and 0.5mg polyethylene glycol (DSPE-PEG2000) injects the anhydrous second of 0.5mL
Disperse in alcohol.25mg menthol powder is taken to be added in the serum bottle for filling 4mL ultrapure water, heating water bath is to 45 DEG C, then again
The aqueous solution that 1mL concentration is 1mg/mL indocyanine green is added.Under the conditions of water bath sonicator, organic-inorganic obtained above is answered
Close lipid and polyethylene glycol ethanol solution be rapidly injected indocyanine green, peppermint alcohol and water mixed liquor in, obtain pre-emulsion.
It is 30w by the Probe Ultrasonic Searching 0.5min(setting ultrasonic power of pre-emulsion ultrasonic cell disintegration instrument, work 3s, stops 3s) after, it obtains
To the silicone grease matter nanoemulsions for containing indocyanine green and menthol.Finally dialysis removes free indocyanine green to get inner cavity packet
It is loaded with indocyanine green and menthol and inorganic silicate shell that surface is covered with nanometer grade thickness and good biocompatibility has
Machine-inorganic compounding lipidic nanoparticles.The structure of the complex lipid nano particle is as shown in Figure 1.
The complex liped obtained in above-described embodiment is measured using Malvern (Malvern) laser particle analyzer and zeta potential instrument
The partial size of matter nano particle is 197.4 ± 6.9nm, and current potential is 12.5 ± 1.8mV of ﹣, and obtains dynamic light scattering as shown in Figure 2
Histogram of particle size distribution.As seen from Figure 2, the nanoparticle for the complex lipid nano particle that melting alcohol injection is prepared
Diameter distribution is relatively narrow, and in 200nm or so, transmission electron microscope photo is as shown in Figure 3.The nano particle of this small particle can penetrate
Tumor vessel wall reaches inside tumor tissues, is expected to realize ultrasonic contrast imaging in tumor locus.
The vitro stability of organic-inorganic complex lipid nano particle is tested:
The organic-inorganic complex lipid nano particle prepared in above-described embodiment is dispersed in the phosphoric acid of PH=7.4 respectively
In buffer and phosphate buffer containing 10% fetal calf serum, it is placed on 37 DEG C of shaking table for 24 hours, every 1h laser particle analyzer
Its change of size is measured, as a result as shown in Figure 4.As can be seen from the figure condition of the nano particle in simulation human internal environment
Under, partial size does not have significant change, illustrates having good stability for nano particle, is expected to reach in vivo circulation for a long time.
Ultraviolet-visible spectrophotometric value of organic-inorganic complex lipid nano particle is measured:
The organic-inorganic complex lipid nano particle prepared in above-described embodiment is prepared according to the concentration of indocyanine green
For 4 μ g/mL, and measure its OD value.As control, free indocyanine green is also configured to its OD value of identical concentration mensuration.
As shown in figure 5, it is 4 μ g/mL that material concentration, which is only 22 μ g/mL(indocyanine green concentration) when, the complex lipid nano particle is in wave
A length of 808nm nearby has apparent absorption peak.Corresponding comparable sodium unentrapped enters the OD of the indocyanine green of nano particle
It is worth roughly equal.It can be seen from the figure that the complex lipid nano particle has apparent light in the case where wavelength is 808nm laser irradiation
Absorption value is expected to convert heat for the light of absorption.
The photothermal conversion efficiency of organic-inorganic complex lipid nano particle is measured:
Photothermal conversion experiment is carried out using the organic-inorganic complex lipid nano particle prepared in above-described embodiment, is such as schemed
Shown in 6, the different indocyanine green solution of setting concentration takes above-mentioned solution 2mL to be placed in quartz colorimetric utensil, outside cuvette respectively
It is wrapped up in paper bag is protected from light, it is 1cm that an area is taken on being protected from light paper2Loophole, using wavelength be 808nm, power be 2w laser
Instrument irradiation, irradiation distance 5cm, irradiated area 1cm2, irradiation time 15min.As shown in fig. 6, each circulation is
30min, preceding 15min use laser irradiation, and rear 15min closes laser, record a temperature value every 30s, obtain such as Fig. 6
Shown curve.It can be seen from the figure that the nano particle still has higher photothermal conversion efficiency in lower concentration, when dense
Nanoparticles solution temperature can reach 65 DEG C or more, it can be achieved that thermotherapy kills the effect of tumor tissues when degree is only 50 μ g/mL.
Experiment is imaged to the external supersonic of organic-inorganic complex lipid nano particle under different frequency:
It takes in above-described embodiment organic-inorganic complex lipid nano particle 1mL obtained to be added to and fills 3mL de aerated water
Dropper in, equally using wavelength be 808nm, power be 2w laser irradiated, irradiation time 5min, irradiation distance
5cm.Irradiation is placed on temperature, with Doppler Sonography diagnostic equipment high frequency probe, mechanical index (MI=0.4),
Depth=3.0cm.Scanning and picture is saved in the case where frequency is f=3.5Hz, 6.5Hz and 8.0Hz respectively, with the physiological saline of equivalent
As control, compare the difference of complex lipid nano particle ultrasonic development under different frequency, as a result as shown in Figure 7.It therefrom can be with
Find out, which there are apparent contrasting effects at different frequencies, and contrasting effects are more under high frequency probe
It is good.The menthol that this complex lipid nano particle of explanation after laser irradiation is wrapped up becomes liquid by solid, then
Liquid volatilizees again becomes a large amount of gas microbubbles, and the nano particle is made to realize the transformation of " solid-liquid-gas " three-phase, Jin Ershi
Now better radiography function.The acoustic contrast agent of this three-phase transformation type had both solved the oversized of ultrasound microbubble contrast agent,
The shortcomings that can only carrying out blood pool Trace imaging, and accomplished the imaging results of microcapsular ultrasound contrast agent.
Test is persistently imaged to the external supersonic of organic-inorganic complex lipid nano particle:
According to the method operation of the external supersonic imaging experiment of organic-inorganic complex lipid nano particle under different frequency
External supersonic persistently images experiment, and records the ultrasonoscopy image of the different time under f=8.0Hz, as shown in Figure 8.By in figure
As it can be seen that the complex lipid nano particle has the lasting development effect up to 25min, this explanation is with organic inorganic compounding lipid
The contrast agent of sheathing material has superior stability and higher resistance to acoustic pressure in ultrasonic sound field.
The present invention is the photothermal conversion property based on indocyanine green, in the case where wavelength is the irradiation of 808nm infrared light, complex liped
The indocyanine green temperature of plastid inner cavity increases, and can kill tumour cell and tissue.But since there are the strong volatilizations of menthol
Property and this very fast problem for losing its function.Therefore, the present invention has synthesized organic-inorganic compound lipid to contain, store
It deposits and based on temperature change puts menthol to be sustained.The menthol wrapped up inside organic-inorganic compound lipid is heated can be into
The circulation transformation of row solid-liquid-gas three phase, generating gas microbubbles can be used for ultrasonic contrast, to reach ultrasonic contrast and photo-thermal therapy
Effect.
This continuous controllable diagnoses and treatment preparation of the present invention is expected to pass through as sensitive temperature response multifunctional carrier
It is injected intravenously the photo-thermal therapy that can be achieved under ultrasonic imaging monitoring, before having extremely wide development in the clinical application of ultrasound
Scape.
The present invention is to be described by embodiment, but do not limit the invention, referring to description of the invention, institute
Other variations of disclosed embodiment, are such as readily apparent that the professional person of this field, such variation should belong to
Within the scope of the claims in the present invention limit.
Claims (2)
1. a kind of preparation method for the diagnosis and treatment preparation for integrating ultrasonic contrast and thermotherapy, it is characterised in that the following steps are included:
1) 1-50mg organic-inorganic complex lipid and 0.1-10mg polyethylene glycol are dissolved in 0.1-1mL dehydrated alcohol；It is described
The structure of organic inorganic compounding lipid are as follows:
,
Alternatively, the structure of organic inorganic compounding lipid are as follows:
；
2) 1-25mg menthol is dissolved in 1-20mL ultrapure water, heating water bath is to 45 DEG C, then the water with 1-10mL indocyanine green
Solution mixing；
3) by the ethanol solution of organic-inorganic complex lipid and polyethylene glycol obtained in step 1) water bath sonicator condition
Under be rapidly injected in the mixed liquor that step 2 obtains；
4) it after Probe Ultrasonic Searching, obtains and has contained indocyanine green and menthol to inner cavity and surface is covered with nanometer grade thickness and biofacies
The organic-inorganic complex lipid nano particle of the good inorganic silicate shell of capacitive.
2. the preparation method of the diagnosis and treatment preparation according to claim 1 for integrating ultrasonic contrast and thermotherapy, feature exist
In: the ultrasonic time in the step 4) is 0.5-5min, ultrasonic power 30W, and the 3s that works stops 3s.
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| CN103480008A (en) * | 2013-09-11 | 2014-01-01 | 中山大学 | Thermal enhancement type organic-inorganic compound lipid nanometer liquid state fluorocarbon ultrasonic contrast agent and preparation method thereof |
| CN103690486A (en) * | 2013-12-27 | 2014-04-02 | 深圳先进技术研究院 | Indocyanine green nano-targeted liposome and preparation method and application thereof |
| CN104474559A (en) * | 2014-12-01 | 2015-04-01 | 中国科学院上海硅酸盐研究所 | Hollow mesoporous prussian blue nano photo-thermal diagnosis and treatment agent with ultrasound contrast function and preparation method of hollow mesoporous prussian blue nano photo-thermal diagnosis and treatment agent |
| CN104826140A (en) * | 2015-04-08 | 2015-08-12 | 中山大学 | Drug-loaded silicone grease ultrasonic contrast agent and its preparation method and use |
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| CN103480008A (en) * | 2013-09-11 | 2014-01-01 | 中山大学 | Thermal enhancement type organic-inorganic compound lipid nanometer liquid state fluorocarbon ultrasonic contrast agent and preparation method thereof |
| CN103690486A (en) * | 2013-12-27 | 2014-04-02 | 深圳先进技术研究院 | Indocyanine green nano-targeted liposome and preparation method and application thereof |
| CN104474559A (en) * | 2014-12-01 | 2015-04-01 | 中国科学院上海硅酸盐研究所 | Hollow mesoporous prussian blue nano photo-thermal diagnosis and treatment agent with ultrasound contrast function and preparation method of hollow mesoporous prussian blue nano photo-thermal diagnosis and treatment agent |
| CN104826140A (en) * | 2015-04-08 | 2015-08-12 | 中山大学 | Drug-loaded silicone grease ultrasonic contrast agent and its preparation method and use |
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