CN105267994A - Nano-scale and ozone-contained microbubble ultrasound contrast agent for kidney cancer and preparation method thereof - Google Patents
Nano-scale and ozone-contained microbubble ultrasound contrast agent for kidney cancer and preparation method thereof Download PDFInfo
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- CN105267994A CN105267994A CN201510711881.2A CN201510711881A CN105267994A CN 105267994 A CN105267994 A CN 105267994A CN 201510711881 A CN201510711881 A CN 201510711881A CN 105267994 A CN105267994 A CN 105267994A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 206010038389 Renal cancer Diseases 0.000 title claims abstract description 15
- 239000002961 echo contrast media Substances 0.000 title abstract description 10
- 208000008839 Kidney Neoplasms Diseases 0.000 title abstract description 3
- 201000010982 kidney cancer Diseases 0.000 title abstract 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims abstract description 127
- 239000000839 emulsion Substances 0.000 claims abstract description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000002604 ultrasonography Methods 0.000 claims abstract description 11
- 229920001661 Chitosan Polymers 0.000 claims abstract description 10
- 241000241413 Propolis Species 0.000 claims abstract description 10
- 229940069949 propolis Drugs 0.000 claims abstract description 10
- 239000012153 distilled water Substances 0.000 claims abstract description 9
- 238000003384 imaging method Methods 0.000 claims abstract description 7
- 239000002872 contrast media Substances 0.000 claims description 73
- 239000003337 fertilizer Substances 0.000 claims description 28
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 14
- 238000005273 aeration Methods 0.000 claims description 13
- 201000010174 renal carcinoma Diseases 0.000 claims description 13
- 239000000725 suspension Substances 0.000 claims description 13
- 108010022355 Fibroins Proteins 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 9
- 239000002131 composite material Substances 0.000 claims description 8
- 238000002242 deionisation method Methods 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 6
- 239000008367 deionised water Substances 0.000 claims 1
- 229910021641 deionized water Inorganic materials 0.000 claims 1
- 239000000243 solution Substances 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 6
- 239000000463 material Substances 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 239000011259 mixed solution Substances 0.000 abstract description 2
- 239000011248 coating agent Substances 0.000 abstract 1
- 238000000576 coating method Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 239000012528 membrane Substances 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 239000002245 particle Substances 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 4
- 230000002902 bimodal effect Effects 0.000 description 2
- 238000002607 contrast-enhanced ultrasound Methods 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 230000000680 avirulence Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 239000000498 cooling water Substances 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000004531 microgranule Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
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Abstract
The invention provides a nano-scale and ozone-contained microbubble ultrasound contrast agent for kidney cancer and a preparation method thereof and belongs to the fields of ultrasound molecular imaging and biomedical engineering. The preparation method is characterized in that the mixed solution of a nano silk protein emulsion, a nano chitosan solution, propolis and distilled water is used to prepare the coating material of the nano-scale and ozone-contained microbubble ultrasound contrast agent, and ozone is used as encapsulating gas; the cavitation effect of dual-frequency compound ultrasound is combined with a nano aerating system to prepare the nano-scale and ozone-contained microbubble ultrasound contrast agent, and simpleness, practicability and high safety are achieved. The nano-scale and ozone-contained microbubble ultrasound contrast agent prepared by the method contains nano-scale and ozone-contained microbubbles even in size and is long in half-life period, stable in performance, large in membrane elasticity, good in biocompatibility, degradable, and ideal for ultrasound contrast.
Description
Technical field
The invention belongs to ultrasound molecular iconography and biomedical engineering field, be specifically related to a kind of nanoscale containing ozone microbubbles acoustic contrast agent and preparation method thereof.
Background technology
Renal carcinoma is one of malignant tumor of China row front ten, and survival rate is lower.The early diagnosis of renal carcinoma and early treatment and its curative effect closely related.Ultrasonic imaging technique, as a kind of noinvasive, low cost, real-time imaging technique, has been widely used in generaI investigation and the clinical diagnosis of tumor of kidney.But due to the sensitivity of conventional ultrasound diagnostic techniques and image resolution ratio all lower, limit the further application of ultrasonic diagnosis.The introducing of micro-/ nano acoustic contrast agent and contrast-enhanced ultrasound technique opens the New Times of ultra sonic imaging, makes ultrasonic diagnosis have higher sensitivity and higher-quality image.But the research of nanoscale ultrasound contrast agents still belongs to the starting stage at present, also have some problems to wait to solve, as the imaging results of nanometer acoustic contrast agent and the optimization of holding time, not only there is higher scattering strength but also can penetrate endothelial gap optimum grain-diameter nanoscale ultrasound contrast agents preparation, how targeting modification same limit contrast agent size, how to optimize frequency range that when obtaining best ultrasonoscopy effect, contrast agent is suitable for or optimum frequency etc.Desirable nanometer acoustic contrast agent should possess following condition: 1. small particle diameter (particle diameter is less than 1 μm); 2. long half time, in body, stable in properties is good; 3. the soft and high resilience of shell; 4. good biocompatibility, few side effects, preparation method is simple, and it is convenient to store.
Also there are some problems in micro/nano level acoustic contrast agent of some Patent data introductions at present and preparation method thereof, as (application number 200610021204.9) in microvesicle ultrasonic biologically-degradable contrast medium containing polymer and preparation method, there is acoustic contrast agent microgranule and compare the weak problem of nanoscale micron order, backscattering echo.A kind of nanoscale lipid microbubble ultrasonic contrast agent of load siRNA and preparation method (application number 201310024514.6), Problems existing is that lipid ultrasonic contrast agent backscattering echo signal is not so good as the strong of gas-filled microbubble acoustic contrast agent.Nanometer ultrasonic/fluorescebimodal bimodal contrast agent, its preparation method and application (application number 201410600818.7), although nanometer ultrasonic/fluorescebimodal bimodal contrast agent has ultrasonic contrast and fluorescence display function, but adopt spray-dired parameter can have a strong impact on the quality of nanometer acoustic contrast agent, and biocompatibility is poor.Therefore, research and preparation have that Nano Particle, long half time, elasticity are large, biocompatibility is strong is the work of the current most important thing containing ozone microbubbles acoustic contrast agent, and this has great social meaning and social value to the contrast-enhanced ultrasound technique Diagnosis and Treat work of China's patients with renal cell carcinoma.
Summary of the invention
In order to solve the problem, the invention provides a kind of nanoscale containing ozone microbubbles acoustic contrast agent and preparation method thereof.Described nanoscale contains ozone microbubbles acoustic contrast agent with the mixed solution of nanometer fibroin emulsion, Nano chitosan solution, propolis and distilled water for coated fertilizer, take ozone as encapsulating gas, have that nano grade air bubbles of uniform size, long half time, stable performance, film elasticity are large, biocompatibility and degradable feature, be the desirable acoustic contrast agent as ultrasonic contrast.Described preparation method adopts the cavitation effect of double frequency composite ultraphonic, and associating nanometer aeration system prepares nanoscale containing ozone microbubbles acoustic contrast agent, and simple, safety is high.
Described nanoscale comprises following step containing the preparation method of ozone microbubbles acoustic contrast agent:
Step one: prepare the coated fertilizer of nanoscale containing ozone microbubbles acoustic contrast agent;
Nanometer fibroin emulsion, Nano chitosan, propolis and distilled water are mixed, stirs 40 ~ 60min with magnetic stirrer, obtain the coated fertilizer of nanoscale containing ozone microbubbles acoustic contrast agent.
Step 2: prepare nanoscale containing ozone microbubbles emulsion;
Nanoscale step one prepared is placed in the cavitation apparatus of double frequency composite ultraphonic containing the coated fertilizer of ozone microbubbles acoustic contrast agent, ozone generating-device is adopted to produce ozone, ozone is passed into nanoscale containing in the coated fertilizer of ozone microbubbles acoustic contrast agent by nanometer aeration system, under the water-cooled condition of deionization, carry out ultrasonic cavitation 15 ~ 30min, obtain nanoscale containing ozone microbubbles emulsion.
The aperture of the aeration head of described nanometer aeration system is less than 5nm.
Step 3: prepare nanoscale containing ozone microbubbles acoustic contrast agent;
The nanoscale prepared in step 2 is contained ozone microbubbles emulsion, to obtain suspension after 2500 ~ 3000rpm centrifugal treating, 3 ~ 5min, collect the nanoscale microbubble solution in suspension intermediate layer in ampere bottle, fill ozone to described ampere bottle and seal ampere bottle bottleneck, namely obtain nanoscale containing ozone microbubbles acoustic contrast agent, and be placed in 0 DEG C of cold cabinet and preserve.
The diameter that described nanoscale contains ozone microbubbles containing nanoscale in ozone microbubbles acoustic contrast agent is 200 ~ 300nm.
Nanoscale, containing an application for ozone microbubbles acoustic contrast agent, for contrast imaging under low frequency ultrasound resonance, may be used for assisting diagnosis renal carcinoma.
The advantage that the present invention possesses is:
(1) coated fertilizer of the present invention all uses nano-macromolecule material, all has biocompatibility and biodegradability, can not produce rejection, avirulence with human body cell.
(2) material of the present invention is biomaterial for medical purpose, nanometer fibroin emulsion, Nano chitosan solution, propolis can film forming, especially the good springiness of nanometer fibroin film, nanoscale not easily breaks containing ozone microbubbles, can image-forming diagnose renal carcinoma under low frequency ultrasound resonance.
(3) adopt the cavitation apparatus of double frequency composite ultraphonic more can strengthen cavitation effect, the nanoscale of preparation is less containing the particle diameter of ozone microbubbles.
(4) ozone of nanoscale microcapsular ultrasound contrast agent encapsulating of the present invention has blood circulation promoting, improves the function of cytokines, at room temperature also has the half-life meeting ultrasonic contrast.
Accompanying drawing explanation
fig. 1 is in the present inventioncavitation apparatus structural representation.
In figure:
1. reactor; 2. ultrasonic cavitation device A; 3. ultrasonic cavitation device B; 4. ultrasonic transducer A; 5. ultrasonic transducer B; 6. cyclic water tank; 7. support.
Detailed description of the invention
Below in conjunction with embodiment, the invention will be further described.
The invention provides the preparation method of a kind of nanoscale containing ozone microbubbles acoustic contrast agent, described preparation method includes the following step:
Step one: prepare the coated fertilizer of nanoscale containing ozone microbubbles acoustic contrast agent;
Nanometer fibroin emulsion 10 ~ 15ml, Nano chitosan 20 ~ 30ml, propolis 5 ~ 10ml and distilled water 200 ~ 300ml are mixed, stirs 40 ~ 60min with magnetic stirrer, obtain the coated fertilizer of nanoscale containing ozone microbubbles acoustic contrast agent, for subsequent use.
Step 2: prepare nanoscale containing ozone microbubbles emulsion;
Nanoscale step one prepared is placed in the cavitation apparatus of double frequency composite ultraphonic containing the coated fertilizer of ozone microbubbles acoustic contrast agent, carries out ultrasonic cavitation 15 ~ 30min, obtains nanoscale containing ozone microbubbles emulsion, for subsequent use.
Described cavitation apparatus as shown in Figure 1, comprise the probe type ultrasonic cavitation device B3 of cylindrical slot type ultrasonic cavitation device A2 and 25kHz of reactor 1,40kHz, ultrasonic transducer A4, ultrasonic transducer B5 and cyclic water tank 6, described reactor 1 and cyclic water tank 6 are fixed respectively by support 7, and it is inner that described reactor 1 is placed in cyclic water tank 6, can be lowered the temperature by the circulating water in cyclic water tank 6 to reactor 1.Described ultrasonic cavitation device A2 places with the ultrasound field of ultrasonic cavitation device B3 is mutually vertical, and the two ends of described ultrasonic cavitation device A2 and ultrasonic cavitation device B3 are connected to ultrasonic transducer A4 and ultrasonic transducer B5.Described reactor 1 is cylindrical, and the diameter of the cross section of reactor 1 is the integral multiple of the half of the ultrasonic wavelength of ultrasonic cavitation device A2, and the height of described reactor 1 is the integral multiple of the half of the ultrasonic wavelength of ultrasonic cavitation device B3.
The coated fertilizer that described nanoscale contains ozone microbubbles acoustic contrast agent is placed in reactor 1, the ozone that flow is 10 ~ 15L/h is passed in reactor 1, under the water-cooled condition of deionization, carry out ultrasonic cavitation 15 ~ 30min by nanometer aeration system, obtain nanoscale containing ozone microbubbles emulsion.
Described ozone is provided by ozone generating-device.Circulating water in described cyclic water tank 6 is deionization cooling water, and temperature is lower than 15 degrees Celsius.
The aperture of the aeration head of described nanometer aeration system is less than 5nm.
Step 3: collect and prepare nanoscale containing ozone microbubbles acoustic contrast agent;
The nanoscale prepared in step 2 is contained ozone microbubbles emulsion, to obtain suspension after 2500 ~ 3000rpm centrifugal treating, 3 ~ 5min, the suspension obtained after centrifugal is divided into three layers: orlop is do not form nanoscale to precipitate containing the coated fertilizer of ozone microbubbles acoustic contrast agent, intermediate layer is that nanoscale contains ozone microbubbles solution, and the superiors are the unstable foam that particle diameter is larger.The nanoscale collecting suspension intermediate layer loads in ampere bottle containing ozone microbubbles solution, ozone is filled to described ampere bottle, nanoscale containing ozone concentration in ozone microbubbles solution at 0.05 ~ 0.1mg/L, and seal ampere bottle bottleneck, namely obtain nanoscale containing ozone microbubbles acoustic contrast agent, and be placed in 0 DEG C of cold cabinet and preserve.Described nanoscale is 200 ~ 300nm containing the diameter of microvesicle in ozone microbubbles acoustic contrast agent.
Provide embodiment below.
embodiment 1
Step one: prepare the coated fertilizer of nanoscale containing ozone microbubbles acoustic contrast agent;
10ml nanometer fibroin emulsion, 20ml Nano chitosan, 5ml propolis and 200ml distilled water are mixed, stirs 40min with magnetic stirrer, obtain the coated fertilizer of nanoscale containing ozone microbubbles acoustic contrast agent, for subsequent use.
Step 2: prepare nanoscale containing ozone microbubbles emulsion;
Nanoscale step one prepared is placed in the cavitation apparatus of double frequency composite ultraphonic containing the coated fertilizer of ozone microbubbles acoustic contrast agent, ozone generating-device is adopted to produce ozone, ozone is passed into nanoscale containing in the coated fertilizer of ozone microbubbles acoustic contrast agent by nanometer aeration system, ultrasonic cavitation 15min is carried out under the water-cooled condition of deionization, obtain nanoscale containing ozone microbubbles emulsion, for subsequent use.
Step 3: prepare nanoscale containing ozone microbubbles acoustic contrast agent;
The nanoscale prepared in step 2 is contained ozone microbubbles emulsion, to obtain suspension after 2500rpm centrifugal treating 3min, the nanoscale collecting suspension intermediate layer contains ozone microbubbles solution in ampere bottle, fill ozone to described ampere bottle and seal ampere bottle bottleneck, namely obtain nanoscale containing ozone microbubbles acoustic contrast agent, and be placed in 0 DEG C of cold cabinet and preserve.It is 200nm that described nanoscale contains ozone microbubbles diameter containing nanoscale in ozone microbubbles acoustic contrast agent.
embodiment 2
Step one: prepare the coated fertilizer of nanoscale containing ozone microbubbles acoustic contrast agent;
15ml nanometer fibroin emulsion, 30ml Nano chitosan, 10ml propolis and 300ml distilled water are mixed, stirs 60min with magnetic stirrer, obtain the coated fertilizer of nanoscale containing ozone microbubbles acoustic contrast agent, for subsequent use.
Step 2: prepare nanoscale containing ozone microbubbles emulsion;
Nanoscale step one prepared is placed in the cavitation apparatus of double frequency composite ultraphonic containing the coated fertilizer of ozone microbubbles acoustic contrast agent, ozone generating-device is adopted to produce ozone, ozone is passed into nanoscale containing in the coated fertilizer of ozone microbubbles acoustic contrast agent by nanometer aeration system, ultrasonic cavitation 30min is carried out under the water-cooled condition of deionization, obtain nanoscale containing ozone microbubbles emulsion, for subsequent use.
Step 3: prepare nanoscale containing ozone microbubbles acoustic contrast agent;
The nanometer prepared in step 2 is contained ozone level microvesicle emulsion, to obtain suspension after 3000rpm centrifugal treating 5min, the nanoscale collecting suspension intermediate layer contains ozone microbubbles solution in ampere bottle, fill ozone to described ampere bottle and seal ampere bottle bottleneck, namely obtain nanoscale containing ozone microbubbles acoustic contrast agent, and be placed in 0 DEG C of cold cabinet and preserve.It is 250nm that described nanoscale contains ozone microbubbles diameter containing nanoscale in ozone microbubbles acoustic contrast agent.
embodiment 3
Step one: prepare the coated fertilizer of nanoscale containing ozone microbubbles acoustic contrast agent;
12.5ml nanometer fibroin emulsion, 25ml Nano chitosan, 7.5ml propolis and 250ml distilled water are mixed, stirs 50min with magnetic stirrer, obtain the coated fertilizer of nanoscale containing ozone microbubbles acoustic contrast agent, for subsequent use.
Step 2: prepare nanoscale containing ozone microbubbles emulsion;
Nanoscale step one prepared is placed in the cavitation apparatus of double frequency composite ultraphonic containing the coated fertilizer of ozone microbubbles acoustic contrast agent, ozone generating-device is adopted to produce ozone, ozone is passed into nanoscale containing in the coated fertilizer of ozone microbubbles acoustic contrast agent by nanometer aeration system, ultrasonic cavitation 22.5min is carried out under the water-cooled condition of deionization, obtain nanoscale containing ozone microbubbles emulsion, for subsequent use.
Step 3: prepare nanoscale containing ozone microbubbles acoustic contrast agent;
The nanometer prepared in step 2 is contained ozone level microvesicle emulsion, to obtain suspension after 2750rpm centrifugal treating 4.5min, the nanoscale collecting suspension intermediate layer contains ozone microbubbles solution in ampere bottle, fill ozone to described ampere bottle and seal ampere bottle bottleneck, namely obtain nanoscale containing ozone microbubbles acoustic contrast agent, and be placed in 0 DEG C of cold cabinet and preserve.It is 300nm that described nanoscale contains ozone microbubbles diameter containing nanoscale in ozone microbubbles acoustic contrast agent.
The result that the nanoscale prepared above-described embodiment is tested containing ozone microbubbles acoustic contrast agent shows, have nanoscale of uniform size in the contrast agent obtained containing ozone microbubbles, long half time stable performance, film elasticity greatly, nanoscale is 200 ~ 300nm containing the particle diameter of ozone microbubbles.Nanoscale not easily breaks containing ozone microbubbles, can image-forming diagnose renal carcinoma under low frequency ultrasound resonance.
Claims (7)
1. for the nanoscale of renal carcinoma containing the preparation method of ozone microbubbles acoustic contrast agent, it is characterized in that: include the following step,
Step one: prepare the coated fertilizer of nanoscale containing ozone microbubbles acoustic contrast agent;
Nanometer fibroin emulsion, Nano chitosan, propolis and distilled water are mixed, stirs 40 ~ 60min with magnetic stirrer, obtain the coated fertilizer of nanoscale containing ozone microbubbles acoustic contrast agent;
Step 2: prepare nanoscale containing ozone microbubbles emulsion;
Coated fertilizer step one prepared is placed in the cavitation apparatus of double frequency composite ultraphonic, ozone generating-device is adopted to produce ozone, in coated fertilizer, ozone is passed into by nanometer aeration system, the flow of ozone is 10 ~ 15L/h, carries out ultrasonic cavitation and obtain nanoscale containing ozone microbubbles emulsion under the water-cooled condition of deionization;
Step 3: prepare nanoscale containing ozone microbubbles acoustic contrast agent;
The nanoscale prepared in step 2 is contained ozone microbubbles emulsion, to obtain suspension after 2500 ~ 3000rpm centrifugal treating, 3 ~ 5min, the nanoscale collecting suspension intermediate layer contains ozone microbubbles solution in ampere bottle, ozone is filled to described ampere bottle, and seal ampere bottle bottleneck, namely obtain nanoscale containing ozone microbubbles acoustic contrast agent, and be placed in 0 DEG C of cold cabinet and preserve; The loading of described ozone is the concentration that nanoscale contains ozone in ozone microbubbles solution is 0.05 ~ 0.1mg/L.
2. a kind of nanoscale for renal carcinoma according to claim 1 is containing the preparation method of ozone microbubbles acoustic contrast agent, it is characterized in that: in step one, nanometer fibroin emulsion is 10 ~ 15ml, Nano chitosan is 20 ~ 30ml, and propolis is 5 ~ 10ml, and distilled water is 200 ~ 300ml.
3. a kind of nanoscale for renal carcinoma according to claim 1 is containing the preparation method of ozone microbubbles acoustic contrast agent, it is characterized in that: the temperature of the deionized water described in step 2 is lower than 15 DEG C, and the described ultrasonic cavitation time is 15 ~ 30min.
4. a kind of nanoscale for renal carcinoma according to claim 1 is containing the preparation method of ozone microbubbles acoustic contrast agent, it is characterized in that: described cavitation apparatus comprises reactor, ultrasonic cavitation device A, ultrasonic cavitation device B, ultrasonic transducer A, ultrasonic transducer B and cyclic water tank, described reactor and cyclic water tank are fixed respectively by support, and described reactor is placed in cyclic water tank inside, described ultrasonic cavitation device A places with the ultrasound field of ultrasonic cavitation device B is mutually vertical, the two ends of described ultrasonic cavitation device A and ultrasonic cavitation device B are connected to ultrasonic transducer A and ultrasonic transducer B, described reactor is cylindrical, and the diameter of the cross section of reactor is the integral multiple of the half of the ultrasonic wavelength of ultrasonic cavitation device A, and the height of described reactor is the integral multiple of the half of the ultrasonic wavelength of ultrasonic cavitation device B, described nanoscale is placed in reactor containing the coated fertilizer of ozone microbubbles acoustic contrast agent.
5. a kind of nanoscale for renal carcinoma according to claim 1 is containing the preparation method of ozone microbubbles acoustic contrast agent, it is characterized in that: the aperture of the aeration head of described nanometer aeration system is less than 5nm.
6. the nanoscale for renal carcinoma contains an ozone microbubbles acoustic contrast agent, it is characterized in that: the diameter that described nanoscale contains ozone microbubbles containing nanoscale in ozone microbubbles acoustic contrast agent is 200 ~ 300nm.
7. for the nanoscale of renal carcinoma containing the application of ozone microbubbles acoustic contrast agent, it is characterized in that: for contrast imaging under low frequency ultrasound resonance.
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| CN201510711881.2A CN105267994B (en) | 2015-10-28 | 2015-10-28 | It is a kind of for nanoscale acoustic contrast agent containing ozone microbubbles of kidney and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109085247A (en) * | 2018-06-27 | 2018-12-25 | 中国计量大学 | A kind of acoustic contrast agent cavitation bubble group resonance state measurement method |
| CN110279432A (en) * | 2019-07-26 | 2019-09-27 | 河南科技大学第一附属医院 | A kind of TCD inspection microbubble contrast preparation and injection device |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103638534A (en) * | 2013-12-02 | 2014-03-19 | 东南大学 | Nanometer lipid ultrasonic contrast agent and preparation method thereof |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103638534A (en) * | 2013-12-02 | 2014-03-19 | 东南大学 | Nanometer lipid ultrasonic contrast agent and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| NAOKI YOSHIMOTO等: ""A new contrast echo imaging method using the crossed beams of two ultrasonic frequencies"", 《PROCEEDINGS OF SYMPOSIUM ON ULTRASONIC ELECTRONICS》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109085247A (en) * | 2018-06-27 | 2018-12-25 | 中国计量大学 | A kind of acoustic contrast agent cavitation bubble group resonance state measurement method |
| CN109085247B (en) * | 2018-06-27 | 2020-10-30 | 中国计量大学 | Ultrasonic contrast agent cavitation bubble group resonance state measurement method |
| CN110279432A (en) * | 2019-07-26 | 2019-09-27 | 河南科技大学第一附属医院 | A kind of TCD inspection microbubble contrast preparation and injection device |
| CN110279432B (en) * | 2019-07-26 | 2021-09-07 | 河南科技大学第一附属医院 | Preparation of microbubble contrast medium and injection device for TCD inspection |
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