CN105854165B - Fixed point drug delivery device in vivo - Google Patents
Fixed point drug delivery device in vivo Download PDFInfo
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- CN105854165B CN105854165B CN201610281636.7A CN201610281636A CN105854165B CN 105854165 B CN105854165 B CN 105854165B CN 201610281636 A CN201610281636 A CN 201610281636A CN 105854165 B CN105854165 B CN 105854165B
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- support rack
- rack type
- type sound
- artificial structure
- fixed point
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/95—Instruments specially adapted for placement or removal of stents or stent-grafts
- A61F2/962—Instruments specially adapted for placement or removal of stents or stent-grafts having an outer sleeve
- A61F2/966—Instruments specially adapted for placement or removal of stents or stent-grafts having an outer sleeve with relative longitudinal movement between outer sleeve and prosthesis, e.g. using a push rod
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
- A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/95—Instruments specially adapted for placement or removal of stents or stent-grafts
- A61F2/958—Inflatable balloons for placing stents or stent-grafts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2210/00—Anatomical parts of the body
- A61M2210/12—Blood circulatory system
Abstract
The present invention provides a kind of fixed point drug delivery devices in vivo, wherein the device includes: support rack type sound artificial structure, conveying device and ultrasonic electronic device in support rack type sound artificial structure's body；Wherein, conveying device in support rack type sound artificial structure body for support rack type sound artificial structure to be delivered to the intravascular of targeted site, and support rack type sound artificial structure is expanded, is attached to the inner wall of blood vessel；Ultrasonic electronic device generates local high field for transmitting ultrasonic exciting support rack type sound meta-surface in vitro；Support rack type sound artificial structure, in advance in conveying device in support rack type sound artificial structure's body, for be transported to targeted site it is intravascular when, using the local high field of support rack type sound meta-surface, endovascular drug particle aggregation will be injected in the inner wall of blood vessel.Above-mentioned technical proposal is realized using the external supersonic drug granule of noninvasive fixed point aggregation in the blood vessels, improves the accuracy for the fixed point administration of human body targeted site.
Description
Technical field
The present invention relates to local delivery technical field, in particular to a kind of fixed point drug delivery device in vivo.
Background technique
Fixed point medicine-feeding technology be in recent years it has been proposed that a kind of novel local conveying drug technique, mainly pass through certain
External force is planted to assemble and discharge drug in appointed part.It is dense that this kind of technology can effectively improve human body target lesions position drug
Degree reduces drug to the toxic side effect of whole body normal tissue, plays a significant role to diseases such as treating cancer, angiocarpy.
Ultrasound has fluctuation effect, and thus derivative ultrasonic imaging technique is a kind of important diagnosis hand of Present clinical medicine
Section has been widely used in a variety of diseases and conventional detection since it has many characteristics, such as lossless, real-time, economical.Ultrasound has
Momentum and energy, the particle in sound field can be acted on by acoustic radiation force, and particle can be pushed under certain physical condition
Movement.Therefore, ultrasound be also used as external force manipulation blood vessel in micro-nano drug granule park and penetrate into lesions position.Currently, super
Be primarily present in sound medicine-feeding technology two kinds fixed point administration methods, below to both methods the shortcomings that and application limitation carry out
It is described below:
One, microparticle technologies are manipulated based on the free found field that energy converter generates:
Scattering due to tissue to sound field, the micro-nano drug granule that can be manipulated by sound field in free space, injection
After in blood vessel, it is difficult to be manipulated in body (in vivo) by identical sound field.The free sound generated based on energy converter is described in detail below
Field manipulation microparticle technologies realize the principle and limitation of fixed point administration.
Sound wave manipulates particle, can be mainly generated using the particle in sound field to sound wave and the effects such as reflect, reflects, absorbs,
The momentum for causing sound field to carry exchanges between sound field and particle, and particle is kept its movement captured by the effect of power.It is existing
Sound trapped particle is mainly the focusing acoustic field directly generated using probe or the stationary field that the opposite placement of two probes is formed.Reason
By the study found that the object in focusing acoustic field will receive along the scattering force effect in acoustic propagation direction and along sound field gradients
Increase the gradient force effect in direction: when scattering force is greater than gradient force, the resultant force that particle is subject to is along acoustic propagation direction；Work as gradient force
Greater than scattering force, resultant force that particle is subject to is along the focal position of focusing acoustic field, therefore particle can arrive at the focus of aggregation sound field
To captured；For stationary field there are antinode and node position, particle can be according to its density, acoustic impedance and surrounding medium in sound field
Proportionate relationship, stablize be in antinode or node positions.
However, being all difficult to manipulate micro-nano drug in human vas by the pop one's head in focusing acoustic field directly generated or stationary field
Grain, the main reason is that scattering of the tissue to sound field, so that focusing field or stationary field in free space is distorted,
Acoustic field focus or nodal point disappear or offset, so that the acoustic radiation force that particle is subject to also changes, cannot grasp in designated position
Control or park cannot achieve accurately fixed point administration in human body.
1991, Vermont university of U.S. Junru Wu experimentally realized sound tweezer effect for the first time, which uses two
A 3.5MHz focusing probe transmitting sound wave placed in opposite directions, forms stable potential well, to capture 270um at common focus
Son.2006, Southern California university of U.S. Jungwoo Lee, K.Kirk Shung et al. proposed single ultrasound
Probe captures short grained sound-line theory model, and realizes that the single focused ultrasonic transducer of 30MHz captures 40um drop in an experiment.
2009, Pennsylyania state university of U.S. Jinjie Shi et al. realized 6um cell aggregation using sound standing surface wave
Effect.2011, related scholar was experimentally observed micro- using the mirror field and position phase of electronic delay regulation ultrasonic surface
Bubble, the aggregation of cell, arrangement and accurate movement effect.
The above method may be implemented using ultrasound manipulation and aggregated particle, still, the scattering due to tissue to sound field,
The micro-nano drug granule that can be manipulated by sound field in free space is difficult in human body after injecting in blood vessel by identical sound field
Manipulation cannot achieve accurately fixed point administration in human body.
Two, microparticle technologies are manipulated based on the sound field that ultrasonic transducer induction sound artificial structure generates:
Currently, related scholar utilizes the hardened structure of phonon crystal (plate surfaces are carved with period grid) surface in resonant frequency
The local sound field of formation realizes capture, arrangement, movement and release to micro particles.However, the device is in one piece of one side
It is carved with the plane manipulation particle of periodical raised plate, if in the system implantable intravascular, drug granule is only capable of being adsorbed on plate surface, nothing
Method is directly contacted with vascular wall, therefore the structure limits its application in the blood vessels, cannot achieve in human body and accurately pinpoints
Administration.
Summary of the invention
The embodiment of the invention provides a kind of fixed point drug delivery devices in vivo, to realize ultrasound aggregation drug in the blood vessels
Grain rises to the accuracy of human body target lesion fixed point administration, which includes: support rack type sound artificial structure, support rack type sound people
Conveying device and ultrasonic electronic device in work structural body；Wherein,
Conveying device in support rack type sound artificial structure's body, for support rack type sound artificial structure to be delivered to the blood of targeted site
In pipe, and support rack type sound artificial structure is expanded, is attached to the inner wall of blood vessel；
Ultrasonic electronic device generates local high field for transmitting ultrasonic exciting support rack type sound artificial structure in vitro；
Support rack type sound artificial structure, in advance in conveying device in support rack type sound artificial structure's body, for being transported to
Targeted site it is intravascular when, using the local high field of support rack type sound meta-surface, endovascular drug granule will be injected
It is gathered in the inner wall of blood vessel.
It is super to realize in the blood vessels the embodiment of the invention also provides a kind of working method of drug delivery device of fixed point in vivo
Sound assembles drug granule, rises to the accuracy of human body target lesion fixed point administration, which includes:
The support rack type sound artificial structure is delivered to the blood of targeted site by conveying device in support rack type sound artificial structure's body
In pipe, and the support rack type sound artificial structure is expanded, is attached to the inner wall of the blood vessel；
Ultrasonic electronic device emits ultrasonic exciting support rack type sound meta-surface in vitro and generates local high field；
Support rack type sound artificial structure in conveying device in support rack type sound artificial structure's body in advance, is being transported to
Targeted site it is intravascular when, using the local high field, endovascular drug particle aggregation will be injected in the blood vessel
Wall.
Compared with prior art, technical solution provided in an embodiment of the present invention has following advantageous effects:
Firstly, being all difficult to manipulate with pop one's head in the prior art the aggregation sound field directly generated or stationary field micro- in human vas
It receives drug granule, cannot manipulate or park in designated position and compare, technical solution provided in an embodiment of the present invention passes through bracket
Support rack type sound artificial structure is delivered to the intravascular of targeted site by conveying device in type sound artificial structure's body, by support rack type sound people
The expansion of work structure, is attached to the blood vessel, and the lower local high field generated is motivated by ultrasound using ultrasonic electronic device, will inject
Endovascular drug particle aggregation realizes the pinpoint administration of drug in the blood vessel of targeted site；
Secondly, capturing particle with using the hardened structure of phonon crystal to generate local sound field in the prior art, drug granule is only capable of
Be adsorbed on one piece and be carved with periodically raised plate surface on one side, can not directly be contacted with vascular wall compared with, the embodiment of the present invention mentions
Support rack type sound artificial structure is delivered to targeted site by conveying device in support rack type sound artificial structure's body by the technical solution of confession
It is intravascular, by support rack type sound artificial structure expand, the blood vessel is attached to, in this way, support rack type sound artificial structure is direct
It is contacted with blood vessel, can make to inject endovascular drug granule fixed point and be gathered in blood vessel, make drug granule park simultaneously
Penetrate into targeted site position.
By it is above-mentioned it is found that technical solution provided by the invention realize in vivo ultrasound aggregation drug granule, improve for
The accuracy of human body target lesion fixed point administration.
Detailed description of the invention
The drawings described herein are used to provide a further understanding of the present invention, constitutes part of this application, not
Constitute limitation of the invention.In the accompanying drawings:
Fig. 1 is the structural schematic diagram for pinpointing drug delivery device in the embodiment of the present invention in vivo；
Fig. 2 a is the schematic diagram that resonating member bar is solid hopkinson bar in the embodiment of the present invention, and Fig. 2 b is total in the embodiment of the present invention
Shake the structural schematic diagram that unit bar is hollow stem, and Fig. 2 c is the schematic diagram that resonating member bar is stratiform bar in the embodiment of the present invention；
Fig. 3 a and 3b are the structural schematic diagrams of support rack type sound artificial structure in the embodiment of the present invention；
Fig. 4 a, 4b and 4c are the structural schematic diagrams of conveying device in support rack type sound artificial structure's body in the embodiment of the present invention；
Wherein, Fig. 4 a is the structural schematic diagram of outer sheath, and Fig. 4 b is the structural schematic diagram of conduit, and Fig. 4 c is outer sheath, conduit, expander
Installation and working state structure schematic diagram with support rack type sound artificial structure；
Fig. 5 is the workflow schematic diagram for pinpointing drug delivery device in the embodiment of the present invention in vivo；
Fig. 6 is the schematic cross-section in medium vessels of the embodiment of the present invention containing support rack type sound artificial structure and drug granule；
Fig. 7 is that ultrasonic action is containing after support rack type sound artificial structure and drug granule in the embodiment of the present invention, drug granule
The schematic cross-section being enriched in around support rack type sound artificial structure；
Fig. 8 is that single diameter is the solid hopkinson bar of D in the local field strength sound field that ultrasonic wave generates in the embodiment of the present invention
Schematic diagram；
Fig. 9 is transmission spectrum of the single PLGA solid hopkinson bar in local field strength sound field in the embodiment of the present invention；
Figure 10 is PLGA solid hopkinson bar its surface pressing field distribution in resonant frequency in the embodiment of the present invention；
Figure 11 is the acoustically radiating that the drug granule that diameter is 0.01D in the embodiment of the present invention is subject in the resonance of PLGA solid hopkinson bar
Penetrate power intensity and direction (arrow) distribution；
Figure 12 is that resonating member rod structure is that ladle wraps up in rubber cylinder in an example of the invention, in the office that ultrasonic wave generates
Schematic diagram in the field strength sound field of domain；
Figure 13 is that ladle wraps up in transmission spectrum of the rubber cylinder in local field strength sound field in the embodiment of the present invention；
Figure 14 is that ladle wraps up in rubber cylinder its surface pressing field distribution in resonant frequency in the embodiment of the present invention；
Figure 15 is that the drug granule that diameter is 0.01D in the embodiment of the present invention is subject to when ladle wraps up in rubber cylinder resonance
Acoustic radiation force intensity and direction (arrow) distribution；
Figure 16 is the flow diagram for pinpointing the working method of drug delivery device in the embodiment of the present invention in vivo.
Specific embodiment
To make the objectives, technical solutions, and advantages of the present invention clearer, right below with reference to embodiment and attached drawing
The present invention is described in further details.Here, exemplary embodiment and its explanation of the invention is used to explain the present invention, but simultaneously
It is not as a limitation of the invention.
Inventor generates local sound field using the hardened structure of phonon crystal in early-stage study and captures particle, due to local high field
In photonic crystal structure surface, the complex environment local area outside support rack type sound artificial structure (other than about 1-2 wavelength) is strong
Field influences less, to may be implemented to manipulate particle under complex environment.But the system is to be carved with periodical protrusion on one side at one piece
Another plane manipulation particle of plate can not be with blood if micro-nano drug granule is only capable of being adsorbed on plate surface in the system implantable intravascular
Tube wall directly contacts, therefore the structure limits its application in the blood vessels.For these disadvantages, the present invention proposes to be based on bracket
The implanted ultrasound fixed point drug delivery device and working method of type sound artificial structure, to realize the manipulation of intravascular drug particle and determine
Point aggregation.It describes in detail below to the fixed point drug delivery device.
Fig. 1 is the structural schematic diagram for pinpointing drug delivery device in the embodiment of the present invention in vivo, as shown in Figure 1, the device includes:
Conveying device 06 and ultrasonic electronic device 02 in support rack type sound artificial structure 04, support rack type sound artificial structure's body；Wherein,
Conveying device 06 in support rack type sound artificial structure's body, for the support rack type sound artificial structure to be delivered to mesh
The intravascular of lesion is marked, and the support rack type sound artificial structure is expanded, is attached to the inner wall of the blood vessel；
It is strong to generate local for transmitting ultrasonic exciting support rack type sound artificial structure in vitro for the ultrasonic electronic device 02
?；
The support rack type sound artificial structure 04 uses in advance in conveying device 06 in support rack type sound artificial structure's body
In be transported to targeted site it is intravascular when, using the local high field of support rack type sound meta-surface, blood vessel will be injected
Inner wall of the interior drug particle aggregation in the blood vessel.
Pinpoint drug delivery device in the embodiment of the present invention in vivo, when work, conveying device 06 in support rack type sound artificial structure's body
Support rack type sound artificial structure 04 is delivered to the intravascular of targeted site, and support rack type sound artificial structure 04 is expanded, is attached to
The inner wall of blood vessel；Ultrasonic electronic device 02 emits ultrasonic exciting support rack type sound artificial structure in vitro and generates local high field；Branch
Frame type sound artificial structure 04 utilize local high field, be transported to targeted site it is intravascular when, using local high field, will inject
Inner wall of the endovascular drug particle aggregation in blood vessel.
Compared with prior art, technical solution provided by the invention has following advantageous effects:
Firstly, being all difficult to manipulate with pop one's head in the prior art the aggregation sound field directly generated or stationary field micro- in human vas
It receives drug granule, cannot manipulate or park in designated position and compare, technical solution provided in an embodiment of the present invention passes through bracket
Support rack type sound artificial structure is delivered to the intravascular of targeted site by conveying device in type sound artificial structure's body, by support rack type sound people
The expansion of work structure, is attached to the blood vessel, the ultrasonic action support rack type sound artificial structure generated using ultrasonic electronic device
Surface generates local high field, will inject endovascular drug particle aggregation in the blood vessel of targeted site, realizes drug
Pinpoint administration；
Secondly, capturing particle with using the hardened structure of phonon crystal to generate local sound field in the prior art, drug granule is only capable of
Be adsorbed on one piece and be carved with periodically raised plate surface on one side, can not directly be contacted with vascular wall compared with, the embodiment of the present invention mentions
Support rack type sound artificial structure is delivered to targeted site by conveying device in support rack type sound artificial structure's body by the technical solution of confession
It is intravascular, by support rack type sound artificial structure expand, the blood vessel is attached to, in this way, support rack type sound artificial structure is direct
It is contacted with blood vessel, can make to inject endovascular drug granule fixed point and be gathered in blood vessel, make drug granule park simultaneously
Penetrate into targeted site position.
By it is above-mentioned it is found that technical solution provided by the invention realize in vivo ultrasound aggregation drug granule, improve for
The accuracy of human body target lesion fixed point administration.
The support rack type sound artificial structure 04 in the embodiment of the present invention is introduced first below.
In the embodiment of the present invention, support rack type sound artificial structure 04 is shrinkable or expansion.Support rack type sound is manually tied below
Structure 04 describes in detail.
In one embodiment, support rack type sound artificial structure may include: the netted knot that multiple resonating member bars are woven into
Structure, in advance in conveying device 06 in support rack type sound artificial structure's body, support rack type sound artificial structure can be net in Fig. 6 or Fig. 7
After shape structure is expanded, resonating member bar is uniformly attached in blood vessel 08, and after expansion, multiple resonating members be can be in parallel
's.In this embodiment, multiple resonating member bars itself constitute reticular structure, expansible to be attached to blood vessel.
In addition, in embodiments of the present invention, the shear wave velocity of resonating member bar is less than the velocity of longitudinal wave of water or blood, in this way
The purpose and principle of implementation are: the resonating member bar that shear wave velocity is less than water can support (this east class Scholtewave in water
Sharp wave) mode, it is the boundary wave existing for solid and fluid boundary, and energy localization is on interface, its sound field in a fluid
Intensity increases exponentially decaying with from interface distance.The velocity of wave of this scholte wave is less than the longitudinal wave and shear wave of water and bar
Speed, only when the shear wave velocity of bar is less than the velocity of longitudinal wave of water, this scholte wave is possible to exist, and
The wavelength of scholte wave meets formula: λ=π D/n, wherein λ is the wavelength of local high field, and D is the circumference of resonating member bar
Diameter, n are the integer more than or equal to 2, i.e. the circumference of bar is the integral multiple of scholte wave wavelength, which can be in bar
Circumferential surface exists.
To sum up, when the shear wave velocity of resonating member bar is less than the velocity of longitudinal wave of water or blood, can just exist and support class
Scholte wave mode generates resonance local sound field, the particles such as aggregation drug.
In one embodiment, the relationship of the wavelength of the circumference overall diameter and local high field of resonating member bar can be with are as follows: and λ=
πD/n；Wherein, λ is the wavelength of local high field, and D is the circumference overall diameter of resonating member bar, and n is the integer more than or equal to 2.
When it is implemented, can be according to the wavelength of the circumference overall diameter and local high field of resonating member bar mentioned above
Relationship λ=π D/n carries out the size and incidence frequency of source of selective reaonance unit bar, is conducive to so in actual work, effectively
Assemble the particles such as drug in ground.
In one embodiment, as shown in Figure 2 c, resonating member bar is stratiform bar, and stratiform bar may include: hard material bar
0431 and the circumferential outer surface coated in hard material bar soft material 0432.
When it is implemented, the advantages of resonating member bar is above-mentioned stratiform bar are as follows: firstly, the stratiform bar of above structure, internal layer
It for hard material bar, is expanded when can satisfy work and is attached to blood vessel, good supporting role can be played；Secondly,
The soft material of the circumferential outer surface coating of hard material bar, can effectively assemble the particles such as drug；In addition, such stratiform rod structure
Both it had been able to satisfy above-mentioned support class Scholte wave mode, the particles such as resonance aggregation drug have been generated, in an implementation again convenient for production
And design.
In one embodiment, as shown in Figure 2 b, resonating member bar can be hollow stem made of hard material.Hard material system
At hollow stem be both able to satisfy above-mentioned support class Scholte wave mode, generate resonance, the particles such as aggregation drug, in an implementation
Good supporting role can be played again.
In one embodiment, the interior diameter value range of above-mentioned hollow stem can be with are as follows: and 0.005 millimeter to 4.95 millimeters,
The outer diameter value range of hollow stem can be with are as follows: 0.01 millimeter to 5 millimeters.Inventor is by a large amount of it is demonstrated experimentally that above-mentioned value
Range can effectively meet above-mentioned support class Scholte wave mode, generate resonance, the particles such as aggregation drug.
In one embodiment, the interior diameter value of above-mentioned hollow stem can be with are as follows: and 0.09 millimeter, the outer diameter value of hollow stem
It can be with are as follows: 0.1 millimeter.Inventor is by a large amount of it is demonstrated experimentally that above-mentioned value can preferably meet above-mentioned support class
Scholte wave mode generates resonance, the particles such as aggregation drug.
In one embodiment, above-mentioned hollow stem can be stainless steel hollow stem.
When it is implemented, stainless steel hollow stem is biocompatible material, will not cause harm to the human body.Certainly, hollow
Bar is also an option that hollow stem made of other biocompatible materials, such as: hollow stem made from magnesium alloy.In addition, hollow
Bar can be combined by homogenous material or multiple material, and the cross section of bar can be arbitrary shape, such as circle, triangle, rectangle
Deng.
In one embodiment, support rack type sound artificial structure may include: intravascular stent matrix and multiple resonating member bars；
Multiple resonating member bars are connected on intravascular stent matrix；In this embodiment, multiple resonating members are evenly connected at blood vessel
On rest body, with the expansion of intravascular stent matrix, it is equably attached to blood vessel.In addition, resonating member bar herein
Shear wave velocity is less than the purpose and principle of the velocity of longitudinal wave of water or blood, and the shear wave velocity for referring to above-mentioned resonating member bar is less than
The purpose and principle of the velocity of longitudinal wave of water or blood.
In one embodiment, as shown in Figure 2 a, resonating member bar can be solid hopkinson bar made of soft material.Soft material was both
Can produce resonance, the particles such as aggregation drug, due to be again it is solid, good supporting role can also be played, after expansion, patch
It is attached to blood vessel, the particles such as drug are effectively gathered in blood vessel.
In one embodiment, solid hopkinson bar can be poly lactide-glycolide acid PLGA solid hopkinson bar.
When it is implemented, solid hopkinson bar is made by poly lactide-glycolide acid PLGA, since PLGA microbot diameter is
0.1 millimeter, its working frequency for generating local area mode of theoretical prediction is 2.578MHz, in the frequency and one embodiment of the invention
The single-element ultrasound transducer of selection is very close, is conducive to subsequent generation resonance to assemble drug granule.Certainly, solid hopkinson bar
Material is not limited to PLGA, can also be the materials such as polydimethylsiloxane, polylactic acid PLA, poly-epsilon-caprolactone PCL, only
Be conducive to subsequent generation resonance to assemble drug granule.
In one embodiment, support rack type sound artificial structure may include: intravascular stent matrix and film cylinder, wherein thin
Film cylinder is connected on intravascular stent matrix, as best shown in figures 3 a and 3b, multiple equally distributed micropores is provided on film cylinder 041
0411.When work, film cylinder 041 is also attached to blood vessel, the equally distributed resonance of micropore 0411 aggregation drug after being expanded
Particle.
When it is implemented, the section of micropore can be arbitrary shape, the circle shown in Fig. 3 a, the rectangle shown in 3b, but
Be confined to round and rectangle, can also be that triangle etc., film can be combined by homogenous material or multiple material.
When it is implemented, the arrangement mode of micropore can be periodic arrangement, arrangement paracycle, defect arrangement.Periodic arrangement
It can be one dimensional line arrangement, two-dimension square arrangement, triangle arrangement, hexagonal arrangement；Paracycle arrangement can be Dimensional Quasiperiodic and
Two-dimentional arrangement paracycle；Defect arrangement can be the one or more non-equal structures of implantation, two-dimension periodic in One Dimension Periodic arrangement
One or more non-equal structures are implanted into arrangement.
By above-mentioned it is found that resonating member bar can be constituted reticular structure with itself, section state such as Fig. 6 or figure after expansion
Shown in 7；Also it can connect on existing intravascular stent matrix, the section state of resonating member bar is also such as Fig. 6 or Fig. 7 after expansion
It is shown；It is also possible to film cylinder to be connected on intravascular stent matrix；Or it can also be using laser etching techniques in intravascular stent
The structures such as the reserved thin membrane regions engraving micropore on matrix.
When it is implemented, support rack type sound artificial structure may is that one layer of soft material of coating on medical vascular stent, straight
A little careful designs are done on diameter, load outer ultrasonic, it can adsorbent particles；Either on the portion of medical vascular stent
Sound artificial structure cylinder (above-mentioned solid hopkinson bar, hollow stem or stratiform bar) or film cylinder etc. are inlayed, outer ultrasonic is loaded, sound is manually tied
Structure cylinder (above-mentioned solid hopkinson bar, hollow stem or stratiform bar) or film cylinder can adsorb drug microparticles.
In one embodiment, support rack type sound artificial structure can manually tie for support rack type sound made of bio-compatible material
Structure.
When it is implemented, support rack type sound artificial structure is made of bio-compatible material, bio-compatible material nothing in human body
Adverse reaction will not cause blood coagulation, haemolysis with blood of human body and tissue compatible, and living tissue will not be inflamed, arrange
Phenomena such as refusing, be carcinogenic.
In one embodiment, support rack type sound artificial structure can be support rack type sound people made of degradable polymeric material
Work structure.
In one embodiment, the soft material in the embodiment of the present invention has drug loading slow releasing function, in this way can benefit
In the bioavilability for improving drug.
When it is implemented, support rack type sound artificial structure is using the purpose of degradable polymeric material: if support rack type sound
Artificial structure is mounted on narrow intravascular, and the support rack type sound artificial structure of degradable polymeric material can not take out, office
It can degrade automatically after portion's medication.But the subsequent incident frequencies that adjust ultrasonic electronic device in use, because of material
Material degradation, diameter and performance will change correspondingly.
In embodiments of the present invention, soft material is meant that: the shear wave velocity of soft material is less than the longitudinal wave speed of water or blood
Degree；Hard material is meant that: the shear wave velocity of hard material is greater than the velocity of longitudinal wave of water or blood.
The ultrasonic electronic device 02 in the embodiment of the present invention is introduced again below.
In one embodiment, ultrasonic electronic device may include:
Signal generator, for generating random waveform (comprising sinusoidal continuous) signal；
Power amplifier obtains the random waveform signal of amplification for amplifying random waveform signal；
Ultrasonic transducer, for generating ultrasonic wave under the excitation of the random waveform signal of amplification.
When it is implemented, the signal specific that signal generator generates is through power amplifier when ultrasonic electronic device 02 works
After amplification, excitation ultrasonic transducer emits ultrasonic wave.
When it is implemented, the transmitting random waveform signal of signal generator can be wideband pulse signal, continuous sinusoidal letter
Number or pulsed sinusoidal signal, wherein the spectral range of signal include sound artificial structure resonant frequency.Signal generator can be with
It is programmable signal generator (AFG3021, Tectronix), power amplifier can be the linear power amplifier of 50dB
(325LA, ENI).Signal generator generates random waveform signal, and random waveform motivates ultrasonic transducer to produce after power amplifier
Raw ultrasonic wave.
The ultrasonic transducer of two kinds of primary structures in the embodiment of the present invention is introduced below as follows.
The first structure: single sonde configuration, i.e., above-mentioned ultrasonic transducer may include:
First probe generates local high field for transmitting ultrasonic exciting support rack type sound meta-surface in vitro, i.e.,
For manipulating drug microparticles, the centre frequency of first probe is 2.5MHz.
When it is implemented, support rack type sound artificial structure 04 uses PLGA solid hopkinson bar due in an embodiment of the invention,
A diameter of 0.1 millimeter, the working frequency of its local field strength generated of theoretical prediction is 2.578MHz, therefore, in the present invention one
In a embodiment, the centre frequency of the first probe of ultrasonic transducer uses 2.5MHz, can ultrasonic transducer be sent out in this way
The ultrasonic wave of the working frequency of support rack type sound artificial structure 04 is penetrated, and then guarantees the subsequent good aggregation to drug granule.
When it is implemented, the ultrasonic transducer can be single-element ultrasound transducer.In single-element ultrasound transducer
Frequency of heart is 2.5MHz, it is, of course, also possible to using other types of ultrasonic transducer, as long as guaranteeing its centre frequency in 2.5MHz
Left and right, can emit the ultrasonic wave of the working frequency of support rack type sound artificial structure 04.
Ultrasonic transducer can also be any in following device: single-element ultrasound transducer, phase array transducer,
Linear array ultrasonic energy converter, convex battle array ultrasonic transducer, interdigital transducer, gaseous substrate PZT (piezoelectric transducer), CMUT (condenser type micro Process
Ultrasonic transducer), as long as meeting the ultrasonic wave that can produce transmitting 04 working frequency of support rack type sound artificial structure, so that support rack type
Sound artificial structure 04 assembles the accurate manipulation of drug granule.
Second of structure: dual probe structure, the i.e. ultrasonic transducer can also include: in addition to including above-mentioned first probe
Second probe is used for providing the frequency for realizing blood vessel and support rack type sound artificial structure's ultrasonic imaging in vitro
It is imaged in realizing, centre frequency can obtain accurate ultrasonic image according to blood vessel and support rack type sound artificial structure's scale and determine.
When it is implemented, the second probe has also been devised in the ultrasonic transducer, which can emit peripheral vascular
Ultrasonic imaging frequency, which is suitable for peripheral vascular ultrasonic imaging, conducive to being clearly imaged enough, is convenient for locating support type sound
Artificial structure.
When it is implemented, above-mentioned ultrasonic transducer can be with are as follows: bimodulus ultrasonic transducer.Certainly, in embodiments of the present invention,
Other types of ultrasonic transducer can also be used, as long as dual probe work may be implemented.
Then, conveying device 06 in support rack type sound artificial structure's body in the embodiment of the present invention is introduced.
Fig. 4 a, 4b and 4c are the structural schematic diagrams of conveying device in support rack type sound artificial structure's body in the embodiment of the present invention；
Wherein, Fig. 4 a is the structural schematic diagram of outer sheath, and Fig. 4 b is the structural schematic diagram of conduit, and Fig. 4 c is outer sheath, conduit, expander
Installation and working state structure schematic diagram with support rack type sound artificial structure.
In one embodiment, as shown in Fig. 4 a, 4b and 4c, conveying device 06 be can wrap in support rack type sound artificial structure's body
It includes:
Outer sheath 061；Support rack type sound artificial structure pre-installs in outer sheath 061；
Conduit 062 is connect with outer sheath 061, for expander 063 to be transported to the intravascular of targeted site position；
Expander 063, be arranged outside conduit 063, for reach targeted site it is intravascular when, outer sheath 061 is pushed away
Support rack type sound artificial structure 04 out expands, and is attached to blood vessel.
When it is implemented, expander 063 can be sacculus, conduit 062 can be foley's tube, support rack type sound artificial structure
04 is preloaded in outer sheath 061, and support rack type sound artificial structure 04 is arranged outside sacculus.When work, conduit 062 reaches intravascular
Area-of-interest (at targeted site) when, outer sheath 061 releases support rack type sound artificial structure 04 and sacculus, and then, sacculus fills
Gas expands support rack type sound artificial structure 04, is tightly attached on vascular wall.After being installed, conduit 062 is withdrawn from, completes support rack type sound
The release process of artificial structure 04.
Based on the same inventive concept, a kind of work of above-mentioned internal fixed point drug delivery device is additionally provided in the embodiment of the present invention
Method, as described in the following examples.The principle and determine in vivo that working method due to pinpointing drug delivery device in vivo solves the problems, such as
Point drug delivery device is similar, therefore the implementation of the working method of fixed point drug delivery device may refer to pinpoint drug delivery device in vivo in vivo
Implement, overlaps will not be repeated.Used below, the software of predetermined function may be implemented in term " unit " or " module "
And/or the combination of hardware.Although device described in following embodiment is preferably realized with software, hardware or soft
The realization of the combination of part and hardware is also that may and be contemplated.
Figure 16 is a kind of flow diagram for pinpointing the working method of drug delivery device in the embodiment of the present invention in vivo, such as Figure 16
Shown, which includes the following steps:
Step 101: the support rack type sound artificial structure is delivered to target by conveying device in support rack type sound artificial structure's body
Lesion it is intravascular, and by the support rack type sound artificial structure expand, be attached to the inner wall of the blood vessel；
Step 102: ultrasonic electronic device emits ultrasonic exciting support rack type sound meta-surface in vitro and generates local
High field；
Step 103: the support rack type sound artificial structure in conveying device in support rack type sound artificial structure's body in advance,
Be transported to targeted site it is intravascular when, using the local high field, endovascular drug particle aggregation will be injected described
The inner wall of blood vessel.
Pinpoint drug delivery device in the embodiment of the present invention in vivo, when work, conveying device 06 in support rack type sound artificial structure's body
Support rack type sound artificial structure 04 is delivered to the intravascular of targeted site, and support rack type sound artificial structure 04 is expanded, is attached to
The inner wall of blood vessel；Ultrasonic electronic device 02 emits ultrasonic exciting support rack type sound artificial structure in vitro and generates local high field；Branch
Frame type sound artificial structure 04 utilize local high field, be transported to targeted site it is intravascular when, using local high field, will inject
Inner wall of the endovascular drug particle aggregation in blood vessel.
Below with reference to Fig. 5,6 and 7, the course of work of fixed point drug delivery device provided in an embodiment of the present invention is introduced,
To illustrate how the present invention is implemented.
Firstly, to be determined to the working frequency of support rack type sound artificial structure 04.With being total to for support rack type sound artificial structure
Unit 042 shake to be illustrated for PLGA solid hopkinson bar.According to the diameter of PLGA solid hopkinson bar, material parameter, theoretical prediction is simultaneously real
The ultrasound works frequency of its surface of test amount generation local field mode.Support rack type sound artificial structure can be placed on water by experimental work
In, resonant frequency is obtained by measurement transmission spectrum.In this specific embodiment, PLGA microbot diameter is 0.1 millimeter, by examination
After testing, its working frequency for generating local area mode of theoretical prediction is 2.578MHz.
Secondly, support rack type sound artificial structure is introduced in the process of body aggregation drug granule, as shown in Fig. 5,6 and 7.
Support rack type sound artificial structure 04 is passed through in support rack type sound artificial structure's body in 06 implantable intravascular of conveying device, and is infused in the blood vessels
Enter drug granule 07, emits the work frequency of ultrasonic excitation support rack type sound artificial structure 04 using ultrasonic electronic device 02 in vitro
The ultrasonic field of rate, so that support rack type sound meta-surface generation local sound field is strong, so that drug particle aggregation around it is adsorbed,
Drug granule 07 is gathered in 08 inner wall of vascular wall.
Fixed point drug delivery device provided in an embodiment of the present invention has already passed through its feasibility of Simulation, below with reference to figure
8 to 11 illustrate its result and advantageous effects.
1) by single diameter for D PLGA (poly lactide-glycolide acid) cylinder (solid hopkinson bar) in sound field for
(as shown in Figure 8) passes through a wideband pulse excitation PLGA solid hopkinson bar；
2) frequency response of PLGA is as shown in figure 9, (c is the velocity of sound in water, and D is at the position that frequency is 0.173 (c/D)
Cylinder (solid hopkinson bar) diameter) there is a resonance extreme value peak, which is resonant frequency；
3) the sonic pressure field intensity distribution in resonant frequency is as shown in Figure 10, and sound field local is on bar surface, far from surface, sound
Pressure decaying；
4) when Figure 11 is resonant frequency, density 1100kg/m^3, the velocity of sound is that 2350m/s partial size is that 1 micro particles exist
Power distribution around PLGA solid hopkinson bar, wherein arrow indicates Impact direction, and color represents stress intensity.The chart is bright, in outer sound
Under field action, due to the local sound field that the resonance of PLGA solid hopkinson bar generates, little particulate (drug granule) can be made in PLGA reality
By the effect of attraction around core bar, it is gathered in around PLGA.Since this is the monomer effect of PLGA, PLGA is real
Core bar, which forms other structures (such as reticular structure of support rack type sound artificial structure), will not influence the local field strength (sound of itself
), the manipulation effect to particle will not be influenced.
In addition, passing through Figure 12 to Figure 15 experimental result recorded and advantageous effects, it may also be said to which the bright present invention is implemented
The fixed point drug delivery device that example provides has already passed through its feasibility of Simulation.Figure 12 is resonated in an example of the invention
Unit rod structure is that ladle wraps up in rubber cylinder, the schematic diagram in the local field strength sound field that ultrasonic wave generates；Figure 13 is the present invention
Ladle wraps up in transmission spectrum of the rubber cylinder in local field strength sound field in embodiment；Figure 14 is that ladle wraps up in rubber in the embodiment of the present invention
Cylinder its surface pressing field distribution in resonant frequency；Figure 15 is that diameter is that the drug granule of 0.01D exists in the embodiment of the present invention
Ladle wraps up in the acoustic radiation force intensity being subject to when rubber cylinder resonance and direction (arrow) distribution.
Finally, it is as follows to carry out additional explanation to technical term and structure being related in the embodiment of the present invention etc.:
1) sound field in the embodiment of the present invention is any sound field that endovascular stent type sound artificial structure can be motivated to resonate,
Sound field form is unlimited.
2) material of support rack type sound artificial structure is the material that can produce resonant acoustic field under a kind of ultrasonic action, it may be assumed that sound
On the surface of the material, its sound field intensity is with exponentially decaying is increased from surface distance in the fluids such as blood, altogether for field energy local
The monomer property of vibration unit is not limited to column, can be solid, hollow, layer structure of multiple material composition etc., support rack type
Sound artificial structure can be surface containing micro-structure, inside containing micro-structure etc., as long as it is total to generate surface local under sound field excitation
Shake field.
3) generate local sound field material include other kinds structure and material, for can outer sound source excitation under can
Generate the material of controllable particle sound field.
4) particle (such as drug granule) manipulated is not limited to the particle that partial size is 0.01D.
5) material of the particle and support rack type sound artificial structure that manipulate can carry out chemistry or bio-modification, increase its adherency
Efficiency and targeting.
6) technical solution provided in an embodiment of the present invention includes but is not limited to intravascular drug aggregation, also extends to other
Under environment, e.g., using sound artificial structure in tumour or outer surface of the skin drug accumulation, the sound field manipulation that artificial structure generates is poly-
Collect the application such as particle.
It is used in narrow blood vessel in addition, fixed point drug delivery device provided in an embodiment of the present invention is unlimited, such as: it can be used for
To the bronchial local administration of human body, the local administration of human rectum.
The embodiment of the present invention realizes following technical effect:
The embodiment of the present invention is realized using support rack type sound artificial structure as " secondary sound source " device for generating local sound field
Aggregation to intravascular drug particle.The embodiment of the present invention includes support rack type sound artificial structure, ultrasonic electronic device, support rack type sound
Conveying device in artificial structure's body.Compared with traditional intravascular stent, support rack type sound artificial structure proposed by the present invention can be by blood
Pipe holder matrix and new technical feature resonating member are constituted, and intravascular stent matrix completes the function of traditional intravascular stent, and resonance is single
Member manipulates particle for when being admitted to targeted site blood vessel, generating local fields；In addition, compared with traditional intravascular stent, the present invention
New technical feature be need ultrasonic electronic device emit ultrasonic exciting support rack type sound artificial structure, to realize drug granule
Fixed point aggregation administration；Compared with the manipulation technology previously based on artificial structure, new technical feature of the invention is to need support rack type
Artificial structure is placed in intravascular by conveying device in sound artificial structure's body, and support rack type sound people provided in an embodiment of the present invention
Work structure can shrink and expand.
The local sound field that the embodiment of the present invention is generated using implanted support rack type sound artificial structure assembles drug granule in body；
The sound field generated the particle more much smaller than structure in gymnastics control is vibrated using implanted support rack type sound artificial structure；Therefore, the skill
Art can be used to implement the targeted delivery of intravascular drug particle, can be used for expanding to the local generated using object resonance
Sound field manipulates the application such as aggregation, detection of micro-nano granules.
Obviously, those skilled in the art should be understood that each module of the above-mentioned embodiment of the present invention or each step can be with
It is realized with general computing device, they can be concentrated on a single computing device, or be distributed in multiple computing devices
On composed network, optionally, they can be realized with the program code that computing device can perform, it is thus possible to by it
Store and be performed by computing device in the storage device, and in some cases, can be held with the sequence for being different from herein
The shown or described step of row, perhaps they are fabricated to each integrated circuit modules or will be multiple in them
Module or step are fabricated to single integrated circuit module to realize.In this way, the embodiment of the present invention be not limited to it is any specific hard
Part and software combine.
The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention, for the skill of this field
For art personnel, the embodiment of the present invention can have various modifications and variations.All within the spirits and principles of the present invention, made
Any modification, equivalent substitution, improvement and etc. should all be included in the protection scope of the present invention.
Claims (21)
1. a kind of fixed point drug delivery device in vivo characterized by comprising support rack type sound artificial structure, support rack type sound artificial structure
Internal conveying device and ultrasonic electronic device；Wherein,
Conveying device in support rack type sound artificial structure's body, for the support rack type sound artificial structure to be delivered to targeted site
It is intravascular, and by the support rack type sound artificial structure expand, be attached to the inner wall of the blood vessel；
It is strong to generate local for transmitting ultrasonic exciting support rack type sound meta-surface in vitro for the ultrasonic electronic device
?；
The support rack type sound artificial structure, in advance in conveying device in support rack type sound artificial structure's body, for defeated
Send to targeted site it is intravascular when, using the local high field, endovascular drug particle aggregation will be injected in the blood vessel
Inner wall；
The resonant frequency of the ultrasound wave packages artificial structure of sound containing support rack type of the ultrasonic electronic device transmitting；The support rack type sound people
Work structure is shrinkable or expansion.
2. fixed point drug delivery device in vivo as described in claim 1, which is characterized in that the support rack type sound artificial structure includes:
The reticular structure that multiple resonating member bars are woven into；The shear wave velocity of the resonating member bar is less than the longitudinal wave speed of water or blood
Degree.
3. fixed point drug delivery device in vivo as claimed in claim 2, which is characterized in that the circumference overall diameter of the resonating member bar
With the relationship of the wavelength of the local high field are as follows: λ=π D/n；Wherein, λ is the wavelength of local high field, and D is the circle of resonating member bar
All diameters, n are the integer more than or equal to 2.
4. fixed point drug delivery device in vivo as claimed in claim 3, which is characterized in that the resonating member bar is stratiform bar, institute
State the soft material that stratiform bar includes: hard material bar and the circumferential outer surface coated in the hard material bar.
5. fixed point drug delivery device in vivo as claimed in claim 3, which is characterized in that the resonating member bar is made of hard material
Hollow stem.
6. fixed point drug delivery device in vivo as claimed in claim 5, which is characterized in that the interior diameter value range of the hollow stem
Are as follows: 0.005 millimeter to 4.95 millimeters, the overall diameter value range of the hollow stem are as follows: 0.01 millimeter to 5 millimeters.
7. fixed point drug delivery device in vivo as claimed in claim 6, which is characterized in that the interior diameter value of the hollow stem are as follows:
0.09 millimeter, the overall diameter value of the hollow stem are as follows: 0.1 millimeter.
8. fixed point drug delivery device in vivo as claimed in claim 5, which is characterized in that the hollow stem is stainless steel hollow stem.
9. fixed point drug delivery device in vivo as described in claim 1, which is characterized in that the support rack type sound artificial structure includes:
Intravascular stent matrix and multiple resonating member bars；Multiple resonating member bars are connected on the intravascular stent matrix；The resonance
The shear wave velocity of unit bar is less than the velocity of longitudinal wave of water or blood.
10. fixed point drug delivery device in vivo as claimed in claim 9, which is characterized in that the resonating member bar is soft material system
At solid hopkinson bar.
11. fixed point drug delivery device in vivo as claimed in claim 10, which is characterized in that the solid hopkinson bar is polylactic acid-glycolic base
Acetate multipolymer PLGA solid hopkinson bar.
12. fixed point drug delivery device in vivo as described in claim 1, which is characterized in that the support rack type sound artificial structure includes:
Intravascular stent matrix and film cylinder, wherein the film cylinder is connected on the intravascular stent matrix, is arranged on the film cylinder
There are multiple equally distributed micropores.
13. the internal fixed point drug delivery device as described in claim 1 to 12 is any, which is characterized in that the support rack type sound is artificial
Structure is support rack type sound artificial structure made of bio-compatible material.
14. the internal fixed point drug delivery device as described in claim 1 to 12 is any, which is characterized in that the support rack type sound is artificial
Structure is support rack type sound artificial structure made of degradable polymeric material.
15. the internal fixed point drug delivery device as described in claim 4 or 10, which is characterized in that it is negative that the soft material has drug
Carry slow releasing function.
16. fixed point drug delivery device in vivo as described in claim 1, which is characterized in that in support rack type sound artificial structure's body
Conveying device includes:
Outer sheath；The support rack type sound artificial structure is mounted in advance in the outer sheath；
Conduit is connect with the outer sheath, for expander to be transported to the intravascular of targeted site；
Expander is arranged outside the conduit, for reach targeted site it is intravascular when, branch that the outer sheath is released
Frame type sound artificial structure expansion, is attached to the blood vessel.
17. fixed point drug delivery device in vivo as described in claim 1, which is characterized in that the ultrasonic electronic device includes:
Signal generator, for generating random waveform signal；
Power amplifier obtains the random waveform signal of amplification for amplifying the random waveform signal；
Ultrasonic transducer, for generating ultrasonic wave, and random waveform frequency packet under the excitation of the random waveform signal of the amplification
The resonant frequency of the artificial structure of sound containing support rack type.
18. fixed point drug delivery device in vivo as claimed in claim 17, which is characterized in that the ultrasonic transducer includes:
First probe generates local high field for transmitting ultrasonic exciting support rack type sound meta-surface in vitro, and described the
The centre frequency of one probe is 2.5MHz.
19. fixed point drug delivery device in vivo as claimed in claim 18, which is characterized in that the ultrasonic transducer is that single array element is super
Sonic transducer.
20. fixed point drug delivery device in vivo as claimed in claim 18, which is characterized in that the ultrasonic transducer further include:
Second probe, for providing the frequency for realizing blood vessel and support rack type sound artificial structure's ultrasonic imaging in vitro.
21. fixed point drug delivery device in vivo as claimed in claim 20, which is characterized in that the ultrasonic transducer is bimodulus ultrasound
Energy converter.
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| CN201610281636.7A CN105854165B (en) | 2016-04-29 | 2016-04-29 | Fixed point drug delivery device in vivo |
| PCT/CN2016/103428 WO2017185695A1 (en) | 2016-04-29 | 2016-10-26 | In-vivo targeted drug administration device and operating method |
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| CN105854165B (en) * | 2016-04-29 | 2019-02-22 | 中国科学院深圳先进技术研究院 | Fixed point drug delivery device in vivo |
| EP3534808A4 (en) * | 2016-11-04 | 2020-06-10 | Les Solutions Médicales Soundbite Inc. | Device for delivering mechanical waves through a balloon catheter |
| CN110339494B (en) * | 2019-07-22 | 2020-10-16 | 山东大学齐鲁医院 | Device and method for in-vivo microbubble manipulation and imaging |
| WO2022104529A1 (en) * | 2020-11-17 | 2022-05-27 | 深圳先进技术研究院 | Generating method and generating system for acoustic tweezers |
| CN114146890B (en) * | 2021-12-03 | 2022-09-13 | 深圳先进技术研究院 | Ultrasonic sound control method and sound tweezers device |
| TWI815292B (en) * | 2022-01-27 | 2023-09-11 | 國立臺灣科技大學 | Needle free delivery system and operation method thereof |
| CN117482419A (en) * | 2023-12-08 | 2024-02-02 | 围美辣妈(北京)健康咨询有限公司 | Plane ultrasonic intelligent fat-reducing physiotherapy instrument based on finite element array physiotherapy head |
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| US20080097281A1 (en) * | 2003-12-15 | 2008-04-24 | Sonanco, Ltd | Ultrasonic Drug-Delivery System |
| CN203861768U (en) * | 2014-03-19 | 2014-10-08 | 中国科学院声学研究所 | Ultrasonic cavitation cloud transporting device |
| CN105214742A (en) * | 2015-10-10 | 2016-01-06 | 中国科学院深圳先进技术研究院 | Based on the microfluid system of artificial structure's sound field and the method for manipulation particulate |
| CN205729963U (en) * | 2016-04-29 | 2016-11-30 | 中国科学院深圳先进技术研究院 | Internal fixed point doser |
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| CN202497168U (en) * | 2012-04-24 | 2012-10-24 | 周宇峰 | Ultrasonic coupling device |
| CN105854165B (en) * | 2016-04-29 | 2019-02-22 | 中国科学院深圳先进技术研究院 | Fixed point drug delivery device in vivo |
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|---|---|---|---|---|
| US20080097281A1 (en) * | 2003-12-15 | 2008-04-24 | Sonanco, Ltd | Ultrasonic Drug-Delivery System |
| CN203861768U (en) * | 2014-03-19 | 2014-10-08 | 中国科学院声学研究所 | Ultrasonic cavitation cloud transporting device |
| CN105214742A (en) * | 2015-10-10 | 2016-01-06 | 中国科学院深圳先进技术研究院 | Based on the microfluid system of artificial structure's sound field and the method for manipulation particulate |
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