WO2017185695A1 - 体内定点给药装置及工作方法 - Google Patents

体内定点给药装置及工作方法 Download PDF

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Publication number
WO2017185695A1
WO2017185695A1 PCT/CN2016/103428 CN2016103428W WO2017185695A1 WO 2017185695 A1 WO2017185695 A1 WO 2017185695A1 CN 2016103428 W CN2016103428 W CN 2016103428W WO 2017185695 A1 WO2017185695 A1 WO 2017185695A1
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WIPO (PCT)
Prior art keywords
stent
type acoustic
blood vessel
artificial structure
delivery device
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PCT/CN2016/103428
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English (en)
French (fr)
Inventor
蔡飞燕
张鹏飞
李飞
郑海荣
孟龙
严飞
王辰
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Shandong University
Shenzhen Institute of Advanced Technology of CAS
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Shandong University
Shenzhen Institute of Advanced Technology of CAS
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Publication of WO2017185695A1 publication Critical patent/WO2017185695A1/zh
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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

Definitions

  • the invention relates to the technical field of local delivery drugs, in particular to an in vivo fixed-point drug delivery device and a working method.
  • the site-specific drug delivery technology is a novel topical drug delivery technology proposed in recent years, which mainly uses some external force to gather and release the drug at a designated site.
  • This kind of technology can effectively improve the drug concentration of target lesions in the human body, reduce the toxic side effects of drugs on normal tissues, and play an important role in the treatment of cancer, cardiovascular and other diseases.
  • Ultrasound has a wave effect, and the derived ultrasound imaging technology is an important diagnostic tool in clinical medicine. Due to its non-destructive, real-time and economic characteristics, it has been widely used in many diseases and routine detection. Ultrasound has momentum and energy, and particles in the sound field can be subjected to acoustic radiation, which can promote particle motion under certain physical conditions. Therefore, the ultrasound can also act as an external force to control the micro-nano drug particles in the blood vessel to stop and infiltrate into the lesion site.
  • the micro-nano drug particles that can be manipulated by the sound field in the free space are difficult to be manipulated in the same sound field in vivo after being injected into the blood vessel.
  • the principle and limitations of fixed-point drug delivery based on the free sound field manipulation particle technology produced by the transducer are described in detail below.
  • Acoustic wave manipulation particles mainly use the particles in the sound field to reflect, refract, and absorb the sound waves, causing the momentum carried by the sound field to exchange between the sound field and the particles, and the particles are subjected to force to cause their motion to be captured.
  • the existing acoustic capture particles mainly use a focused sound field directly generated by the probe or a standing wave field formed by the two probes facing each other.
  • Theoretical studies have found that objects in the focused sound field are affected by the scattering force along the direction of sound propagation and the gradient force along the direction of the gradient of the sound field: when the scattering force is greater than the gradient force, the resultant force of the particles is along the direction of sound propagation; When the gradient force is greater than the scattering force, the resultant force of the particles is along the focus position of the focused sound field, so the particles will reach the focus of the concentrated sound field and be captured; the standing wave field has the antinode and the node position, and the particles will be in the sound field according to their density.
  • the proportional relationship between the acoustic impedance and the surrounding medium is stable at the antinode or wave node position.
  • the focused sound field or the standing wave field directly generated by the probe is difficult to manipulate the micro-nano drug particles in the human blood vessels.
  • the main reason is the scattering of the sound field by human tissues, which causes the distortion of the aggregate field or standing wave field in free space.
  • the focus of the sound field or the wave node disappears or shifts, so that the acoustic radiation force of the particle also changes, and it cannot be manipulated or parked at a specified position, and accurate precise site administration in the human body cannot be achieved.
  • the above method can realize the manipulation and agglomeration of particles by using ultrasound, but due to the scattering of the sound field by the human body tissue, the micro-nano drug particles that can be manipulated by the sound field in the free space are difficult to be manipulated by the same sound field in the human body after being injected into the blood vessel. Accurate fixed-point administration in the human body cannot be achieved.
  • the researchers have realized the capture, alignment, movement and release of micro-particles by using the local sound field formed on the surface of the phononic crystal plate structure (the surface of the plate is engraved with a periodic grid) at the resonance frequency.
  • the device is a planar manipulation particle engraved with a periodic convex plate on one side. If the system is implanted in a blood vessel, the drug particles can only be adsorbed on the surface of the plate and cannot directly contact the blood vessel wall, so the structure limits its structure. In intravascular applications, accurate site-directed administration in the human body cannot be achieved.
  • the embodiment of the invention provides an in vivo fixed-point drug delivery device for realizing ultrasonic aggregation of drug particles in a blood vessel, and improving the accuracy of site-specific administration of a target lesion of the human body.
  • the device comprises: a stent-type acoustic artificial structure and a stent-type sound.
  • a stent-type acoustic artificial structure in vivo delivery device for conveying a stent-type acoustic artificial structure into a blood vessel of a target lesion, and expanding the stent-type acoustic artificial structure and attaching to the inner wall of the blood vessel;
  • An ultrasonic electronic device for transmitting a localized strong field in an externally excited ultrasonically excited stent-type acoustic artificial structure
  • the stent-type acoustic artificial structure is pre-installed in the stent-type acoustic artificial structure in vivo delivery device, and is used for injecting into the blood vessel when the local strong field of the surface of the stent-type acoustic artificial structure is used when being transported into the blood vessel of the target lesion.
  • the drug particles accumulate on the inner wall of the blood vessel.
  • the embodiment of the invention further provides a working method of the in-situ fixed-point drug delivery device, which is used for realizing ultrasonic aggregation of drug particles in a blood vessel, and improving the accuracy of site-specific administration of a target lesion of the human body, the working method comprising:
  • the stent-type acoustic artificial structure in vivo delivery device transports the stent-type acoustic artificial structure into the blood vessel of the target lesion, and expands the stent-type acoustic artificial structure and attaches to the inner wall of the blood vessel;
  • the ultrasonic electronic device emits a local strong field on the surface of the ultrasonic excitation bracket type acoustic artificial structure
  • a stent-type acoustic artificial structure preloaded in the stent-type acoustic artificial structure in vivo delivery device which is used to collect drug particles injected into the blood vessel by using the local strong field when being transported into the blood vessel of the target lesion.
  • the inner wall of the blood vessel The inner wall of the blood vessel.
  • the stent-type acoustic artificial structure in vivo delivery device delivers the stent-type acoustic artificial structure to the blood vessel of the target lesion, expands the stent-type acoustic artificial structure, attaches to the inner wall of the blood vessel, and uses localized strong ultrasonic excitation to generate local strong In the field, the drug particles injected into the blood vessel are collected on the inner wall of the blood vessel of the target lesion, and the precise administration of the drug is achieved;
  • the local acoustic field is used to capture the particles by using the phononic crystal plate structure, and the drug particles can only be adsorbed on one side of the surface of the periodic convex plate and cannot be directly contacted with the blood vessel wall.
  • the stent-type acoustic artificial structure is transported into the blood vessel of the target lesion through the stent-type acoustic artificial structure in vivo delivery device, and the stent-type acoustic artificial structure is expanded and attached to the inner wall of the blood vessel, so that the stent-type acoustic artificial
  • the structure directly contacts the inner wall of the blood vessel, and the drug particles injected into the blood vessel can be concentrated on the inner wall of the blood vessel, so that the drug particles are parked and infiltrated into the target lesion site.
  • the technical solution provided by the present invention realizes ultrasonic aggregation of drug particles in vivo, and improves the accuracy of site-specific administration of target lesions for human body.
  • FIG. 1 is a schematic view showing the structure of an in vivo drug delivery device according to an embodiment of the present invention
  • FIG. 2a is a schematic view showing a resonance rod as a solid rod in the embodiment of the present invention
  • FIG. 2b is a schematic structural view showing a resonance unit rod as a hollow rod in the embodiment of the present invention
  • FIG. 2c is a layered rod of the resonance unit rod in the embodiment of the present invention
  • 3a and 3b are schematic structural views of a bracket type acoustic artificial structure in an embodiment of the present invention.
  • FIG. 4a, 4b and 4c are schematic views showing the structure of a stent-type acoustic artificial structure in vivo delivery device according to an embodiment of the present invention
  • FIG. 4a is a schematic structural view of the outer sheath tube
  • FIG. 4b is a structural schematic view of the catheter
  • FIG. 4c is an outer sheath tube.
  • Figure 5 is a schematic view showing the working flow of the in vivo drug delivery device in the embodiment of the present invention.
  • Figure 6 is a schematic cross-sectional view showing a stent-type acoustic artificial structure and drug particles in a blood vessel according to an embodiment of the present invention
  • FIG. 7 is a schematic cross-sectional view showing the enrichment of drug particles around a scaffold-type acoustic artificial structure after ultrasonic excitation includes a scaffold-type acoustic artificial structure and drug particles in an embodiment of the present invention
  • Figure 8 is a schematic view showing a single solid rod of diameter D in a localized field strength sound field generated by ultrasonic waves in an embodiment of the present invention
  • Figure 10 is a diagram showing the surface pressure field distribution of a PLGA solid rod at a resonance frequency in an embodiment of the present invention
  • Figure 11 is a diagram showing the distribution of the intensity and direction (arrow) of the acoustic radiation force of the drug particles having a diameter of 0.01 D during the resonance of the PLGA solid rod in the embodiment of the present invention
  • Figure 12 is a schematic view showing a structure of a resonant unit rod in the form of a steel-wrapped rubber cylinder in a local field-strength sound field generated by ultrasonic waves in an example of the present invention
  • Figure 13 is a transmission spectrum of a steel-wrapped rubber cylinder in a local field strength sound field in an embodiment of the present invention
  • Figure 14 is a diagram showing the surface pressure field distribution of a steel-wrapped rubber cylinder at a resonance frequency in an embodiment of the present invention
  • Figure 15 is a diagram showing the distribution of sound radiation intensity and direction (arrow) of a drug particle having a diameter of 0.01D in the case of a steel-wrapped rubber cylinder in the embodiment of the present invention
  • Figure 16 is a flow chart showing the working method of the in vivo drug delivery device in the embodiment of the present invention.
  • the inventor used the phononic crystal plate structure to generate local sound field to capture particles. Because the local strong field is on the surface of the phononic crystal structure, the complex environment outside the stent-type acoustic artificial structure (about 1-2 wavelengths) It has little effect on the local strong field and can control the particles in complex environments. However, the system is another planar manipulation particle engraved with a periodic convex plate on one side. If the system is implanted in a blood vessel, the micro-nano drug particles can only be adsorbed on the surface of the plate and cannot directly contact the blood vessel wall, so the structure Limit its use in blood vessels.
  • the present invention proposes an implantable ultrasonic fixed-point drug delivery device and a working method based on a stent-type acoustic artificial structure to achieve manipulation and fixed-point aggregation of intravascular drug particles.
  • the fixed point drug delivery device will be described in detail below.
  • FIG. 1 is a schematic structural view of an in vivo dosing device according to an embodiment of the present invention. As shown in FIG. 1, the device includes: a bracket type acoustic artificial structure 04, a bracket type acoustic artificial structure internal delivery device 06, and an ultrasonic electronic device 02; ,
  • the stent-type acoustic artificial structure in vivo delivery device 06 is configured to deliver the stent-type acoustic artificial structure 04 into a blood vessel of a target lesion, and expand the stent-type acoustic artificial structure 04 to be attached to the blood vessel Inner wall
  • the ultrasonic electronic device 02 is configured to generate an external strong field by transmitting an ultrasonic excitation scaffold type acoustic artificial structure 04 in vitro;
  • the stent-type acoustic artificial structure 04 is pre-installed in the stent-type acoustic artificial structure in vivo delivery device 06 for utilizing the local strong surface of the stent-type acoustic artificial structure 04 when being transported into the blood vessel of the target lesion.
  • drug particles injected into the blood vessel are collected on the inner wall of the blood vessel.
  • the in-vivo fixed-point drug delivery device in operation, the stent-type acoustic artificial structure in vivo delivery device 06 delivers the stent-type acoustic artificial structure 04 to the blood vessel of the target lesion, and expands and attaches the stent-type acoustic artificial structure 04.
  • the ultrasonic electronic device 02 emits an ultrasonic excitation scaffold-type acoustic artificial structure 04 to generate a local strong field in vitro; the scaffold-type acoustic artificial structure 04 utilizes a local strong field, and is utilized when being transported to the blood vessel of the target lesion.
  • the local strong field collects the drug particles injected into the blood vessel on the inner wall of the blood vessel.
  • the stent-type acoustic artificial structure in vivo delivery device transports the stent-type acoustic artificial structure into the blood vessel of the target lesion, expands the stent-type acoustic artificial structure, attaches to the inner wall of the blood vessel, and uses the ultrasonic excitation device to generate the ultrasonic excitation bracket type acoustic artificial
  • the surface of the structure produces a local strong field, and the drug particles injected into the blood vessel are collected on the inner wall of the blood vessel of the target lesion, thereby realizing precise administration of the drug;
  • the local acoustic field is used to capture the particles by using the phononic crystal plate structure, and the drug particles can only be adsorbed on one side of the surface of the periodic convex plate and cannot be directly contacted with the blood vessel wall.
  • the stent-type acoustic artificial structure is transported into the blood vessel of the target lesion through the stent-type acoustic artificial structure in vivo delivery device, and the stent-type acoustic artificial structure is expanded and attached to the inner wall of the blood vessel, so that the stent-type acoustic artificial
  • the structure directly contacts the inner wall of the blood vessel, and the drug particles injected into the blood vessel can be concentrated on the inner wall of the blood vessel, so that the drug particles are parked and infiltrated into the target lesion site.
  • the technical solution provided by the present invention realizes ultrasonic aggregation of drug particles in vivo, and improves the accuracy of site-specific administration of target lesions for human body.
  • the stent-type acoustic artificial structure 04 in the embodiment of the present invention will first be described below.
  • the stent-type acoustic artificial structure 04 can be contracted or expanded.
  • the bracket type acoustic artificial structure 04 will be described in detail below.
  • the stent-type acoustic artificial structure may include: a mesh structure in which a plurality of resonant unit rods are woven, pre-installed in the stent-type acoustic artificial structure in vivo delivery device 06, and the stent-type acoustic artificial structure may be FIG. 6 or After the mesh structure is expanded in Fig. 7, the resonance unit rod is uniformly attached to the inner wall 08 of the blood vessel, and after expansion, the plurality of resonance units may be parallel.
  • the plurality of resonant unit rods themselves constitute a mesh structure that is expandably attached to the inner wall of the blood vessel.
  • the shear wave speed of the resonance unit rod is smaller than the longitudinal wave speed of water or blood
  • the purpose and principle of the implementation is that the resonance unit rod whose transverse wave speed is smaller than water can support the Scholte wave in the water.
  • Wave mode which is an interface wave existing at the interface between solid and fluid, whose energy is localized at the interface, and its sound field intensity decays exponentially with increasing distance from the interface.
  • the wave velocity of this scholte wave is less than the longitudinal and shear wave velocities of water and rod.
  • the resonant unit rod is a layered rod
  • the layered rod may include a hard material rod 0431 and a soft material layer 0432 coated on the circumferential outer surface of the hard material rod.
  • the advantage that the resonant unit rod is the above-mentioned layered rod is as follows: Firstly, the layered rod of the above structure has an inner layer of a hard material rod, which can be expanded and attached to the inner wall of the blood vessel during work, and can be excellent. Supporting effect; secondly, the soft material layer coated on the outer circumferential surface of the hard material rod can effectively aggregate particles such as medicine; in addition, such a layered rod structure can satisfy the above-mentioned support type Scholte wave mode, generate resonance aggregation medicine, etc. The granules are easy to manufacture and design in practice.
  • the resonant unit rod can be a hollow rod made of a hard material.
  • the hollow rod made of hard material can satisfy the above-mentioned support type Scholte wave mode, generate resonance, aggregate drugs and other particles, and can play a good supporting role in the implementation.
  • the inner diameter of the hollow rod may range from 0.005 mm to 4.95 mm, and the outer diameter of the hollow rod may range from 0.01 mm to 5 mm.
  • the inventors have proved through a large number of experiments that the above range of values can effectively satisfy the above-mentioned support-like Scholte wave mode, generating resonance, agglomerating drugs and the like.
  • the inner diameter of the hollow rod may be: 0.09 mm, and the outer diameter of the hollow rod may be 0.1 mm.
  • the inventors have proved through a large number of experiments that the above values can better satisfy the above-mentioned support-like Scholte wave mode, generating resonance, agglomerating drugs and the like.
  • the hollow rod may be a stainless steel hollow rod.
  • the stainless steel hollow rod is a biocompatible material and will not cause harm to the human body.
  • the hollow rod can also be selected from hollow rods made of other biocompatible materials, such as hollow rods made of magnesium alloy.
  • the hollow rod may be composited from a single material or a plurality of materials, and the cross section of the rod may be any shape such as a circle, a triangle, a rectangle, or the like.
  • the stent-type acoustic artificial structure may include: a blood vessel stent base and a plurality of resonant unit rods; the plurality of resonant unit rods are coupled to the blood vessel stent base; in this embodiment, the plurality of resonant units are uniformly connected
  • the vascular stent base is evenly attached to the inner wall of the blood vessel as the vascular stent base expands.
  • the purpose and principle of the transverse wave velocity of the resonant unit rod is less than the longitudinal wave velocity of water or blood, please refer to the purpose and principle of the transverse wave velocity of the above resonant unit rod being less than the longitudinal wave velocity of water or blood.
  • the resonant unit rod can be a solid rod made of a soft material.
  • Soft materials can generate resonance, aggregate drugs and other particles. Because they are solid, they can also play a good supporting role. After expansion, they are attached to the inner wall of blood vessels to effectively collect particles such as drugs on the inner wall of blood vessels.
  • the solid rod can be a polylactic acid-glycolic acid copolymer PLGA solid rod.
  • the solid rod is made of polylactic acid-glycolic acid copolymer PLGA. Since the PLGA microrod has a diameter of 0.1 mm, it is theoretically predicted to generate a local mode operating frequency of 2.579 MHz, which is in one embodiment of the present invention.
  • the single-element ultrasound transducers selected are very similar, which facilitates subsequent resonance to aggregate drug particles.
  • the material of the solid rod is not limited to PLGA, and may be a material such as polydimethylsiloxane PDMS, polylactic acid PLA, poly- ⁇ -caprolactone PCL, as long as it is advantageous for subsequent resonance to aggregate the drug particles.
  • the stent-type acoustic artificial structure may include: a blood vessel stent base and a film cylinder, wherein the film cylinder is attached to the blood vessel stent base, as shown in FIGS. 3a and 3b, the film cylinder 041 is provided with a plurality of uniform distributions Micropores 0411. During operation, the film cartridge 041 is also attached to the inner wall of the blood vessel after being expanded, and the uniformly distributed micropores 0411 resonate to aggregate the drug particles.
  • the cross section of the micropores may be any shape, the circle shown in FIG. 3a, the rectangle shown in FIG. 3b, but not limited to a circle and a rectangle, and may also be a triangle or the like, and the film may be a single material or a plurality of The material is compounded.
  • the arrangement of the micropores may be a periodic arrangement, a quasi-periodic arrangement, or a defect arrangement.
  • the periodic arrangement may be a one-dimensional line arrangement, a two-dimensional square arrangement, a triangular arrangement, and a hexagonal arrangement;
  • the quasi-periodic arrangement may be a one-dimensional quasi-period and a two-dimensional quasi-periodic arrangement;
  • the defect arrangement may be one or more implanted in the one-dimensional periodic arrangement One non-identical structure, one or more non-identical structures are implanted in a two-dimensional periodic arrangement.
  • the resonant unit rod can form a mesh structure by itself, and the expanded cross-sectional state is as shown in FIG. 6 or FIG. 7; it can also be connected to the existing blood vessel support base, and the cross-sectional state of the resonant unit rod after expansion is also as 6 or FIG. 7; the film cylinder may be attached to the base of the blood vessel support; or a structure such as micropores may be engraved on the reserved film area on the base of the blood vessel support by laser etching.
  • the stent-type acoustic artificial structure may be: coating a soft material on the medical blood vessel stent, and performing precise design on the diameter, and loading the external ultrasound to adsorb the particles; or in the medical blood vessel stent
  • the acoustic artificial structural cylinder (the above-mentioned solid rod, hollow rod or layered rod) or the film cylinder, etc.
  • the acoustic artificial structural cylinder can be loaded with external ultrasonic, acoustic artificial structural cylinder (the above solid rod, hollow rod or layered rod) or a film cylinder.
  • Adsorb drug particles the above-mentioned solid rod, hollow rod or layered rod
  • the stent-type acoustic artificial structure can be a stent-type acoustic artificial structure made of a biocompatible material.
  • the scaffold-type acoustic artificial structure is made of biocompatible materials, and the biocompatible material has no adverse reactions in the human body, is compatible with human blood and tissues, does not cause coagulation and hemolysis, and does not cause inflammation or platooning of living tissues. Rejection, carcinogenesis, etc.
  • the stent-type acoustic artificial structure can be a stent-type acoustic artificial structure made of a degradable polymer material.
  • the soft material in the embodiment of the present invention has a drug load sustained release effect, which can be beneficial to improve the bioavailability of the drug.
  • the purpose of the scaffold-type acoustic artificial structure using the degradable polymer material is: if the stent-type acoustic artificial structure is installed in a narrow blood vessel, the stent-type acoustic artificial structure of the degradable polymer material may not be taken out, and the topical medication may be used. It can be degraded automatically. However, the incident frequency of the ultrasonic electronic device is adjusted during use, and the diameter and performance change as the material degrades.
  • the meaning of the soft material is that the transverse wave velocity of the soft material is smaller than the longitudinal wave velocity of water or blood; the meaning of the hard material is that the shear wave velocity of the hard material is greater than the longitudinal wave velocity of water or blood.
  • the ultrasonic electronic device 02 in the embodiment of the present invention will be further described below.
  • the ultrasound electronic device can include:
  • a signal generator for generating an arbitrary waveform (including sinusoidal continuous) signals
  • a power amplifier for amplifying an arbitrary waveform signal to obtain an amplified arbitrary waveform signal
  • An ultrasonic transducer for generating ultrasonic waves under excitation of an amplified arbitrary waveform signal.
  • the ultrasonic electronic device 02 when the ultrasonic electronic device 02 is in operation, the specific signal generated by the signal generator is amplified by the power amplifier, and the ultrasonic transducer is excited to emit the ultrasonic wave.
  • the signal waveform of the signal generator may be a broadband pulse signal, a continuous sinusoidal signal, or a pulsed sinusoidal signal, wherein the spectral range of the signal includes the resonant frequency of the acoustic artificial structure.
  • the signal generator can be a programmable signal generator (AFG3021, Tectronix) and the power amplifier can be a 50dB linear power amplifier (325LA, ENI).
  • the signal generator generates an arbitrary waveform signal, and the arbitrary waveform is excited by the ultrasonic transducer to generate ultrasonic waves after passing through the power amplifier.
  • the first structure a single probe structure, that is, the above ultrasonic transducer may include:
  • the first probe is configured to generate a local strong field on the surface of the ultrasonic excitation scaffold type acoustic artificial structure, that is, to manipulate the drug particles, and the center frequency of the first probe is 2.5 MHz.
  • the bracket-type acoustic artificial structure 04 adopts a PLGA solid rod with a diameter of 0.1 mm, and theoretically predicts that the local field strength generated by the operating frequency is 2.478 MHz, and therefore,
  • the center frequency of the first probe of the ultrasonic transducer is 2.5 MHz, so that the ultrasonic transducer can emit ultrasonic waves at the operating frequency of the bracket-type acoustic artificial structure 04, thereby ensuring good subsequent aggregation of the drug particles.
  • the ultrasonic transducer may be a single-element ultrasonic transducer.
  • the center frequency of the single-element ultrasonic transducer is 2.5MHz.
  • other types of ultrasonic transducers can be used.
  • the center frequency is about 2.5MHz, the ultrasonic wave of the working frequency of the bracket-type acoustic artificial structure 04 can be emitted. Just fine.
  • the ultrasonic transducer can also be any of the following devices: single-element ultrasonic transducer, phased array ultrasonic transducer, linear array ultrasonic transducer, convex array ultrasonic transducer, interdigital transducer, The gas matrix piezoelectric transducer, CMUT (capacitive micromachined ultrasonic transducer), as long as it meets the ultrasonic wave that can generate the operating frequency of the emission bracket type acoustic artificial structure 04, enables the bracket type acoustic artificial structure 04 to accurately control the concentration of the drug particles. can.
  • CMUT capactive micromachined ultrasonic transducer
  • the second structure the dual probe structure, that is, the ultrasonic transducer includes, in addition to the first probe, the following:
  • the second probe is used to provide a frequency for realizing ultrasound imaging of the blood vessel and the stent type acoustic artificial structure in vitro, that is, for imaging, and the center frequency can be determined by obtaining accurate ultrasonic images according to the scale of the blood vessel and the stent type acoustic artificial structure.
  • the ultrasonic transducer is also designed with a second probe, which can emit a surface blood vessel ultrasound imaging frequency, which is suitable for surface blood vessel ultrasound imaging, which is convenient for clear imaging, and is convenient for positioning stent type. Acoustic artificial structure.
  • the ultrasonic transducer may be: a dual mode ultrasonic transducer.
  • other types of ultrasonic transducers can also be used as long as the dual probe operation can be realized.
  • FIG. 4a, 4b and 4c are schematic views showing the structure of a stent-type acoustic artificial structure in vivo delivery device according to an embodiment of the present invention; wherein, FIG. 4a is a schematic structural view of the outer sheath tube, FIG. 4b is a structural schematic view of the catheter, and FIG. 4c is an outer sheath tube. Schematic diagram of the installation and working state of the duct, expander and bracket type acoustic artificial structure.
  • the stent-type acoustic artificial body delivery device 06 can comprise:
  • bracket type acoustic artificial structure is pre-installed in outer sheath tube 061;
  • a catheter 062 coupled to the outer sheath 061 for delivering the dilator 063 to the blood vessel of the target lesion site;
  • the dilator 063 is disposed outside the catheter 063 for expanding the stent-type acoustic artificial structure 04 from which the sheath tube 061 is pushed out when it reaches the blood vessel of the target lesion, and attaches it to the inner wall of the blood vessel.
  • the expander 063 can be a balloon
  • the catheter 062 can be a balloon catheter
  • the stent-type acoustic artificial structure 04 is pre-installed in the outer sheath tube 061
  • the stent-type acoustic artificial structure 04 is disposed outside the balloon.
  • the outer sheath tube 061 pushes out the stent-type acoustic artificial structure 04 and the balloon, and then the balloon inflates to expand the stent-type acoustic artificial structure 04, closely adhering On the wall of the blood vessel.
  • the catheter 062 is withdrawn to complete the release process of the stent-type acoustic artificial structure 04.
  • an embodiment of the present invention also provides a working method of the above-described in vivo drug delivery device, as described in the following embodiments. Since the working principle of the fixed-point drug delivery device in the body solves the problem similarly to the in vivo drug delivery device, the implementation of the working method of the in vivo drug delivery device can be referred to the implementation of the in vivo drug delivery device, and the repeated description will not be repeated.
  • the term "unit” or "module” may implement a combination of software and/or hardware of a predetermined function.
  • the apparatus described in the following embodiments is preferably implemented in software, hardware, or a combination of software and hardware, is also possible and contemplated.
  • Figure 16 is a flow chart showing the working method of the in vivo drug delivery device in the embodiment of the present invention. As shown in Figure 16, the working method includes the following steps:
  • Step 101 The stent-type acoustic artificial structure in vivo delivery device transports the stent-type acoustic artificial structure into a blood vessel of a target lesion, and expands the stent-type acoustic artificial structure and attaches to the inner wall of the blood vessel;
  • Step 102 The ultrasonic electronic device emits a local strong field on the surface of the ultrasonic excitation bracket type acoustic artificial structure.
  • Step 103 A stent-type acoustic artificial structure pre-installed in the stent-type acoustic artificial structure in vivo delivery device, and when being transported into the blood vessel of the target lesion, the local strong field is used to inject the drug particles into the blood vessel. Gathered on the inner wall of the blood vessel.
  • the in-vivo fixed-point drug delivery device in operation, the stent-type acoustic artificial structure in vivo delivery device 06 delivers the stent-type acoustic artificial structure 04 to the blood vessel of the target lesion, and expands and attaches the stent-type acoustic artificial structure 04.
  • the ultrasonic electronic device 02 emits an ultrasonic excitation scaffold-type acoustic artificial structure to generate a local strong field in vitro
  • the scaffold-type acoustic artificial structure 04 utilizes a local strong field to utilize the localized field when being transported to the blood vessel of the target lesion.
  • the strong field of the field concentrates the drug particles injected into the blood vessel on the inner wall of the blood vessel.
  • the operating frequency of the bracket type acoustic artificial structure 04 is determined.
  • the resonance unit 042 of the bracket type acoustic artificial structure is taken as an example of a PLGA solid rod.
  • the ultrasonic working frequency of the local field mode generated on the surface is theoretically predicted and experimentally measured.
  • Bracket type acoustic artificial knot The structure is placed in water and the resonant frequency is obtained by measuring the transmission spectrum.
  • the PLGA microrod has a diameter of 0.1 mm. After the test, it is theoretically predicted that the local frequency is 2.578 MHz.
  • the process of accumulating drug particles in the body of the stent-type acoustic artificial structure is introduced, as shown in Figures 5, 6 and 7.
  • the stent-type acoustic artificial structure 04 is implanted into the blood vessel through the stent-type acoustic artificial structure in vivo delivery device 06, and the drug particle 07 is injected into the blood vessel, and the working frequency of the ultrasonic excitation bracket-type acoustic artificial structure 04 is emitted by the ultrasonic electronic device 02 in vitro.
  • the ultrasonic field causes the surface acoustic field strength of the scaffold-type acoustic artificial structure to adsorb the surrounding drug particles and collect the drug particles 07 on the inner wall of the blood vessel wall 08.
  • the fixed-point drug delivery device provided by the embodiment of the present invention has been verified by numerical simulation, and the results and beneficial technical effects thereof will be described below with reference to Figs.
  • a PLGA (polylactic acid-glycolic acid copolymer) cylinder (solid rod) of a single diameter D is taken as an example in the sound field (as shown in Fig. 8), and the PLGA solid rod is excited by a broadband pulse;
  • the intensity distribution of the sound pressure field at the resonance frequency is as shown in Fig. 10.
  • the sound field is localized on the surface of the rod, away from the surface, and the sound pressure is attenuated;
  • Figure 11 shows the force distribution around the PLGA solid rod with a density of 1100 kg/m ⁇ 3 and a sound velocity of 2350 m/s with a particle size of 1 micron.
  • the arrow indicates the direction of force and the color represents the strength of the force.
  • the figure shows that under the action of the external sound field, due to the local sound field generated by the resonance of the PLGA solid rod, small particles (drug particles) can be attracted around the PLGA solid rod and gather around the PLGA. Since this is the monomer effect of PLGA, the PLGA solid rods constitute other structures (such as the mesh structure of the bracket-type acoustic artificial structure), etc., which do not affect their local field strength (sound field), nor will they affect the pair. The handling effect of the particles.
  • FIG. 12 is a schematic view showing a structure of a resonant unit rod as a steel-wrapped rubber cylinder in a local field-strength sound field generated by ultrasonic waves in an example of the present invention
  • Figure 13 is a view showing a steel-wrapped rubber cylinder in a local field-strength sound field in the embodiment of the present invention
  • Figure 14 is a surface pressure field distribution of a steel-wrapped rubber cylinder at a resonance frequency in an embodiment of the present invention
  • Figure 15 is a sample of a drug having a diameter of 0.01D in the embodiment of the present invention. Sound radiation force intensity and direction (arrow) distribution.
  • the sound field in the embodiment of the present invention is any sound field that can excite the resonance of the intravascular stent-type acoustic artificial structure, and the sound field morphology is not limited.
  • the material of the bracket type acoustic artificial structure is a material that can generate a resonance sound field under ultrasonic excitation, that is, the sound field energy is locally on the surface of the material, and the sound field intensity in the fluid such as blood increases exponentially with increasing distance from the surface.
  • the monomer property of the resonance unit is not limited to the columnar body, and may be a solid, hollow, layered structure composed of a plurality of materials, etc.
  • the bracket type acoustic artificial structure may be a surface containing a microstructure, an internal micro structure, or the like, as long as it can be excited in the sound field. The surface local resonance field can be generated.
  • the material that produces the local sound field contains other types of structures and materials that are materials that can produce a steerable particle sound field under excitation from an external sound source.
  • the manipulated particles are not limited to particles having a particle diameter of 0.01D.
  • Controlled particles and scaffold-type acoustic artificial structures can be chemically or biologically modified to increase their adhesion efficiency and targeting.
  • the technical solutions provided by the embodiments of the present invention include, but are not limited to, intravascular drug aggregation, and can also be extended to other environments, for example, using sound artificial structures to accumulate drugs on the tumor or the outer surface of the skin, and the sound field controlled by the artificial structure controls the aggregated particles. And other applications.
  • the fixed-dose administration device provided by the embodiment of the present invention is not limited to use in a narrow blood vessel, for example, it can also be used for local administration to human bronchus and local administration of human rectum.
  • the embodiment of the invention utilizes a bracket-type acoustic artificial structure as a "secondary sound source" device for generating a local sound field, thereby realizing aggregation of intravascular drug particles.
  • Embodiments of the invention include a bracket-type acoustic artificial structure, an ultrasonic electronic device, and a stent-type acoustic artificial structure internal delivery device.
  • the stent-type acoustic artificial structure proposed by the invention can be composed of a vascular stent base and a new technical characteristic resonance unit, and the vascular stent base completes the function of the traditional vascular stent, and the resonance unit is used for being sent to the target lesion blood vessel.
  • the local field manipulation particle is generated; in addition, compared with the conventional blood vessel stent, the new technical feature of the present invention is that the ultrasonic electronic device is required to emit an ultrasonic excitation stent-type acoustic artificial structure to realize fixed-point aggregation administration of the drug particle; In contrast to the manipulation technique of the artificial structure, the new technical feature of the present invention is that the stent-type acoustic artificial structure in vivo delivery device is required to dispose the artificial structure in the blood vessel, and the stent-type acoustic artificial structure provided by the embodiment of the present invention can be contracted and expanded.
  • the local sound field generated by the implantable bracket type acoustic artificial structure is used to aggregate the drug particles in the body; the sound field generated by the vibration of the implanted bracket type acoustic artificial structure is used to manipulate the particles which are much smaller than the structure in the body; therefore, the Techniques can be used to achieve targeted delivery of intravascular drug particles, and can also be extended to applications that utilize local sound fields generated by object resonance to manipulate aggregation, detection, and the like of micro-nanoparticles.
  • modules or steps of the embodiments of the present invention can be used.
  • a general-purpose computing device which may be centralized on a single computing device or distributed over a network of multiple computing devices.
  • they may be implemented by program code executable by the computing device, such that Storing them in a storage device is performed by a computing device, and in some cases, the steps shown or described may be performed in an order different than that herein, or separately fabricated into individual integrated circuit modules, or Multiple of these modules or steps are fabricated as a single integrated circuit module.
  • embodiments of the invention are not limited to any specific combination of hardware and software.

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Abstract

一种体内定点给药装置及工作方法，其中，该装置包括：支架型声人工结构（04）、支架型声人工结构体内输送装置（06）和超声电子装置（02）；其中，支架型声人工结构体内输送装置（06），用于将支架型声人工结构（04）输送至目标病灶的血管内，并将支架型声人工结构（04）扩张，贴附在血管的内壁；超声电子装置（02），用于在体外发射超声波激励支架型声人工结构（04）表面产生局域强场；支架型声人工结构（04），预装在支架型声人工结构体内输送装置（06）内，用于在被输送至目标病灶的血管内时，利用支架型声人工结构（04）表面的局域强场，将注入血管内的药物颗粒聚集在血管的内壁。上述技术方案实现了利用体外超声在血管内无创定点聚集药物颗粒，提高了为人体目标病灶定点给药的准确性。

Description

体内定点给药装置及工作方法 技术领域
本发明涉及局部输送药物技术领域，特别涉及一种体内定点给药装置及工作方法。
背景技术
定点给药技术是近年来人们提出的一种新型局部输送药物技术，其主要是通过某种外力来聚集并释放药物于指定部位。这类技术能够有效提高人体目标病灶部位药物浓度，降低药物对全身正常组织的毒副作用，对治疗癌症、心血管等疾病具有重要作用。
超声具有波动效应，由此衍生的超声成像技术是当前临床医学一种重要的诊断手段，由于其具有无损、实时、经济等特征，已经广泛应用于多种疾病及常规检测中。超声具有动量和能量，处于声场中的微粒能够受到声辐射力作用，在一定物理条件下能够推动粒子运动。因此，超声还可以作为外力操控血管中微纳药物颗粒停驻并渗入病灶部位。目前，超声给药技术中主要存在两种定点给药的方法，下面对这两种方法的缺点和应用局限性进行介绍如下：
一、基于换能器产生的自由声场操控微粒技术：
由于人体组织对声场的散射，自由空间中能够被声场操控的微纳药物颗粒，注入血管中后，很难在体内(in vivo)被相同的声场操控。下面详细介绍基于换能器产生的自由声场操控微粒技术实现定点给药的原理及局限性。
声波操控粒子，主要是利用声场中的颗粒会对声波产生反射、折射、吸收等效应，导致声场携带的动量在声场与颗粒之间发生交换，颗粒受到力的作用使其运动被捕获。现有声捕获粒子主要是利用探头直接产生的聚焦声场或两个探头相向放置形成的驻波场。理论研究发现，处于聚焦声场中的物体会受到沿着声传播方向的散射力作用和沿着声场梯度增加方向的梯度力作用：当散射力大于梯度力，颗粒受到的合力沿着声传播方向；当梯度力大于散射力，颗粒受到的合力沿着聚焦声场的焦点位置，因此颗粒会抵达聚集声场的焦点从而被捕获；驻波场存在波腹和波节位置，颗粒在声场中会根据其密度、声阻抗与周围介质的比例关系，稳定处于波腹或波节点位置。
然而，由探头直接产生的聚焦声场或驻波场都很难操控人体血管内微纳药物颗粒，其主要原因是人体组织对声场的散射，使得在自由空间中的聚集场或驻波场发生畸变， 声场焦点或波节点消失或偏移，从而微粒受到的声辐射力也发生改变，不能在指定位置操控或停驻，无法实现人体内精确地定点给药。
1991年，美国Vermont大学Junru Wu首次在实验上实现了声镊效应，该实验采用两个相向放置的3.5MHz聚焦探头发射声波，在共同焦点处形成稳定势阱，从而捕获270μm粒子。2006年，美国Southern California大学Jungwoo Lee，K.Kirk Shung等人提出单个超声探头捕获小颗粒的声线理论模型，并在实验中实现30MHz单个聚焦超声探头捕获40μm液滴。2009年，美国Pennsylyania州立大学Jinjie Shi等人利用声表面驻波实现了6μm细胞聚集效应。2011年，有关学者利用电子延迟调控表面超声波的反射场和位相，在实验上观察到微泡、细胞的聚集、排列和精确移动效应。
上述方法可以实现利用超声操控和聚集颗粒，但是，由于人体组织对声场的散射，自由空间中能够被声场操控的微纳药物颗粒，注入血管中后，很难在人体内被相同的声场操控，无法实现人体内精确地定点给药。
二、基于超声换能器诱导声人工结构产生的声场操控微粒技术：
目前，有关学者利用声子晶体板结构(板子表面刻有周期栅格)在共振频率时表面形成的局域声场，实现了对微米粒子的捕获、排列、移动和释放。然而，该装置是在一块一面刻有周期性凸起板的平面操控微粒，该系统若植入血管内，药物颗粒仅能吸附在板表面，无法与血管壁直接接触，因此该结构限制了其在血管内的应用，无法实现人体内精确地定点给药。
发明内容
本发明实施例提供了一种体内定点给药装置，用以在血管内实现超声聚集药物颗粒，提高为人体目标病灶定点给药的准确性，该装置包括：支架型声人工结构、支架型声人工结构体内输送装置和超声电子装置；其中，
支架型声人工结构体内输送装置，用于将支架型声人工结构输送至目标病灶的血管内，并将支架型声人工结构扩张，贴附在血管的内壁；
超声电子装置，用于在体外发射超声波激励支架型声人工结构产生局域强场；
支架型声人工结构，预装在支架型声人工结构体内输送装置内，用于在被输送至目标病灶的血管内时，利用支架型声人工结构表面的局域强场，将注入血管内的药物颗粒聚集在血管的内壁。
本发明实施例还提供了一种体内定点给药装置的工作方法，用以在血管内实现超声聚集药物颗粒，提高为人体目标病灶定点给药的准确性，该工作方法包括：
支架型声人工结构体内输送装置将所述支架型声人工结构输送至目标病灶的血管内，并将所述支架型声人工结构扩张，贴附在所述血管的内壁；
超声电子装置在体外发射超声波激励支架型声人工结构表面产生局域强场；
预装在所述支架型声人工结构体内输送装置内的支架型声人工结构，在被输送至目标病灶的血管内时，利用所述局域强场，将注入血管内的药物颗粒聚集在所述血管的内壁。
与现有技术相比较，本发明实施例提供的技术方案，具有如下有益技术效果：
首先，与现有技术中探头直接产生的聚集声场或驻波场都很难操控人体血管内微纳药物颗粒，不能在指定位置操控或停驻相比较，本发明实施例提供的技术方案，通过支架型声人工结构体内输送装置将支架型声人工结构输送至目标病灶的血管内，将支架型声人工结构扩张，贴附在所述血管内壁，利用超声电子装置超声激励下产生的局域强场，将注入血管内的药物颗粒聚集在目标病灶的血管内壁，实现了药物的精确定点给药；
其次，与现有技术中采用声子晶体板结构产生局域声场捕获微粒，药物颗粒仅能吸附在一块一面刻有周期性凸起板表面，无法与血管壁直接接触相比较，本发明实施例提供的技术方案，通过支架型声人工结构体内输送装置将支架型声人工结构输送至目标病灶的血管内，将支架型声人工结构扩张，贴附在所述血管内壁，这样，支架型声人工结构直接与血管内壁接触，可以使注入血管内的药物颗粒定点聚集在血管内壁，使药物颗粒停驻并渗入目标病灶部位。
通过上述可知，本发明提供的技术方案实现了体内超声聚集药物颗粒，提高了为人体目标病灶定点给药的准确性。
附图说明
此处所说明的附图用来提供对本发明的进一步理解，构成本申请的一部分，并不构成对本发明的限定。在附图中：
图1是本发明实施例中体内定点给药装置的结构示意图；
图2a是本发明实施例中共振单元杆为实心杆的示意图，图2b是本发明实施例中共振单元杆为空心杆的结构示意图，图2c是本发明实施例中共振单元杆为层状杆的示意图；
图3a和3b是本发明实施例中支架型声人工结构的结构示意图；
图4a、4b和4c是本发明实施例中支架型声人工结构体内输送装置的结构示意图；其中，图4a为外鞘管的结构示意图，图4b为导管的结构示意图，图4c为外鞘管、导管、扩张器和支架型声人工结构的安装及工作状态结构示意图；
图5是本发明实施例中体内定点给药装置的工作流程示意图；
图6是本发明实施例中血管中含有支架型声人工结构和药物颗粒的截面示意图；
图7是本发明实施例中超声激励含有支架型声人工结构和药物颗粒后，药物颗粒富集在支架型声人工结构周围的截面示意图；
图8是本发明实施例中单个直径为D的实心杆在超声波产生的局域场强声场中的示意图；
图9是本发明实施例中单个PLGA实心杆在局域场强声场中的透射谱；
图10是本发明实施例中PLGA实心杆在共振频率时其表面压力场分布；
图11是本发明实施例中直径为0.01D的药物颗粒在PLGA实心杆共振时受到的声辐射力强度和方向(箭头)分布；
图12是本发明一个实例中共振单元杆结构为钢包裹橡胶圆柱，在超声波产生的局域场强声场中的示意图；
图13是本发明实施例中钢包裹橡胶圆柱在局域场强声场中的透射谱；
图14是本发明实施例中钢包裹橡胶圆柱在共振频率时其表面压力场分布；
图15是本发明实施例中直径为0.01D的药物颗粒在钢包裹橡胶圆柱共振时受到的声辐射力强度和方向(箭头)分布；
图16是本发明实施例中体内定点给药装置的工作方法的流程示意图。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚明白，下面结合实施方式和附图，对本发明做进一步详细说明。在此，本发明的示意性实施方式及其说明用于解释本发明，但并不作为对本发明的限定。
发明人在前期研究中采用声子晶体板结构产生局域声场捕获微粒，由于局域强场处于声子晶体结构表面，在支架型声人工结构外(约1-2个波长以外)的复杂环境对局域强场影响不大，可以实现在复杂环境下操控微粒。但是该系统是在一块一面刻有周期性凸起板的另一平面操控微粒，该系统若植入血管内，微纳药物颗粒仅能吸附在板表面，无法与血管壁直接接触，因此该结构限制了其在血管内的应用。针对这些缺点，本发明提出基于支架型声人工结构的植入式超声定点给药装置及工作方法，以实现血管内药物颗粒的操控和定点聚集。下面对该定点给药装置进行详细介绍。
图1是本发明实施例中体内定点给药装置的结构示意图，如图1所示，该装置包括：支架型声人工结构04、支架型声人工结构体内输送装置06和超声电子装置02；其中，
所述支架型声人工结构体内输送装置06，用于将所述支架型声人工结构04输送至目标病灶的血管内，并将所述支架型声人工结构04扩张，贴附在所述血管的内壁；
所述超声电子装置02，用于在体外发射超声波激励支架型声人工结构04产生局域强场；
所述支架型声人工结构04，预装在所述支架型声人工结构体内输送装置06内，用于在被输送至目标病灶的血管内时，利用支架型声人工结构04表面的局域强场，将注入血管内的药物颗粒聚集在所述血管的内壁。
本发明实施例中体内定点给药装置，工作时，支架型声人工结构体内输送装置06将支架型声人工结构04输送至目标病灶的血管内，并将支架型声人工结构04扩张，贴附在血管的内壁；超声电子装置02在体外发射超声波激励支架型声人工结构04产生局域强场；支架型声人工结构04利用局域强场，在被输送至目标病灶的血管内时，利用局域强场，将注入血管内的药物颗粒聚集在血管的内壁。
与现有技术相比较，本发明提供的技术方案，具有如下有益技术效果：
首先，与现有技术中探头直接产生的聚集声场或驻波场都很难操控人体血管内微纳药物颗粒，不能在指定位置操控或停驻相比较，本发明实施例提供的技术方案，通过支架型声人工结构体内输送装置将支架型声人工结构输送至目标病灶的血管内，将支架型声人工结构扩张，贴附在所述血管内壁，利用超声电子装置产生的超声激励支架型声人工结构表面产生局域强场，将注入血管内的药物颗粒聚集在目标病灶的血管内壁，实现了药物的精确定点给药；
其次，与现有技术中采用声子晶体板结构产生局域声场捕获微粒，药物颗粒仅能吸附在一块一面刻有周期性凸起板表面，无法与血管壁直接接触相比较，本发明实施例提供的技术方案，通过支架型声人工结构体内输送装置将支架型声人工结构输送至目标病灶的血管内，将支架型声人工结构扩张，贴附在所述血管内壁，这样，支架型声人工结构直接与血管内壁接触，可以使注入血管内的药物颗粒定点聚集在血管内壁，使药物颗粒停驻并渗入目标病灶部位。
通过上述可知，本发明提供的技术方案实现了体内超声聚集药物颗粒，提高了为人体目标病灶定点给药的准确性。
下面首先对本发明实施例中的支架型声人工结构04进行介绍。
本发明实施例中，支架型声人工结构04可收缩或者扩张。下面对支架型声人工结构04进行详细介绍。
在一个实施例中，支架型声人工结构可以包括：多个共振单元杆编织成的网状结构，预装在支架型声人工结构体内输送装置06内，支架型声人工结构可以是图6或图7中网状结构被扩张后，共振单元杆均匀贴附在血管内壁08内，扩张后，多个共振单元可以是平行的。在该实施例中，多个共振单元杆自身构成网状结构，可扩张贴附在血管内壁。
另外，在本发明实施例中，共振单元杆的横波速度小于水或血液的纵波速度，这样实施的目的及原理是：横波速度小于水的共振单元杆在水中可以支持类Scholte wave(斯东利波)模式，它是在固体和流体界面存在的界面波，其能量局域在界面上，在流体中其声场强度随着离界面距离增大成指数衰减。这个scholte wave的波速小于水和杆的纵波和横波速度，只有当杆的横波速度小于水的纵波速度的时候，这个scholte wave才有可能存在，且scholte wave的波长满足公式：λ＝πD/n，其中，λ为局域强场的波长，D为共振单元杆的圆周直径，n为大于或等于2的整数，即杆的圆周是scholte wave波长的整数倍，该模式即可在杆圆周表面存在。
综上，当共振单元杆的横波速度小于水或血液的纵波速度时，才会存在支持类Scholte wave模式，产生共振局域声场，聚集药物等颗粒。
在一个实施例中，共振单元杆的圆周外直径与局域强场的波长的关系可以为：λ＝πD/n；其中，λ为局域强场的波长，D为共振单元杆的圆周外直径，n为大于或等于2的整数。
具体实施时，可以按照上述提到的共振单元杆的圆周外直径与局域强场的波长的关系λ＝πD/n，进行选择共振单元杆的尺寸和入射声源频率，这样有利于实际工作时，有效地聚集药物等颗粒。
在一个实施例中，如图2c所示，共振单元杆为层状杆，层状杆可以包括：硬材料杆0431和涂覆在硬材料杆的圆周外表面的软材料层0432。
具体实施时，共振单元杆为上述层状杆的优点为：首先，上述结构的层状杆，内层为硬材料杆，可以满足工作时被扩张贴附在血管内壁，可以起到很好的支撑作用；其次，在硬材料杆的圆周外表面涂覆的软材料层，可以有效聚集药物等颗粒；另外，这样的层状杆结构既能满足上述支持类Scholte wave模式，产生共振聚集药物等颗粒，在实施中又便于制作和设计。
在一个实施例中，如图2b所示，共振单元杆可以为硬材料制成的空心杆。硬材料制成的空心杆既能满足上述支持类Scholte wave模式，产生共振，聚集药物等颗粒，在实施中又可以起到很好的支撑作用。
在一个实施例中，上述空心杆的内直径取值范围可以为：0.005毫米至4.95毫米，空心杆的外径取值范围可以为：0.01毫米至5毫米。发明人经过大量的实验证明，上述取值范围可以有效满足上述支持类Scholte wave模式，产生共振，聚集药物等颗粒。
在一个实施例中，上述空心杆的内直径取值可以为：0.09毫米，空心杆的外径取值可以为：0.1毫米。发明人经过大量的实验证明，上述取值可以更好地满足上述支持类Scholte wave模式，产生共振，聚集药物等颗粒。
在一个实施例中，上述空心杆可以为不锈钢空心杆。
具体实施时，不锈钢空心杆为生物兼容性材料，不会对人体造成伤害。当然，空心杆还可以选择其它生物兼容性材料制成的空心杆，例如：镁合金制得的空心杆。另外，空心杆可由单一材料，或者多种材料复合而成，杆的横截面可为任意形状，如圆形、三角形、矩形等。
在一个实施例中，支架型声人工结构可以包括：血管支架基体和多个共振单元杆；多个共振单元杆连接在血管支架基体上；在该实施例中，多个共振单元均匀地连接在血管支架基体上，随着血管支架基体的扩张，均匀地贴附在血管内壁。另外，此处共振单元杆的横波速度小于水或血液的纵波速度的目的及原理，请参见上述共振单元杆的横波速度小于水或血液的纵波速度的目的及原理。
在一个实施例中，如图2a所示，共振单元杆可以为软材料制成的实心杆。软材料既可以产生共振，聚集药物等颗粒，由于又是实心的，还可以起到良好的支撑作用，扩张后，贴附在血管内壁，将药物等颗粒有效地聚集在血管内壁。
在一个实施例中，实心杆可以为聚乳酸-羟基乙酸共聚物PLGA实心杆。
具体实施时，实心杆由聚乳酸-羟基乙酸共聚物PLGA制得，由于PLGA微杆直径为0.1毫米，理论预测其产生局域模式的工作频率为2.578MHz，该频率与本发明一个实施例中选用的单阵元超声换能器十分相近，有利于后续产生共振以聚集药物颗粒。当然，实心杆的材料不局限于PLGA，还可以为聚二甲基硅氧烷PDMS、聚乳酸PLA、聚ε-己内酯PCL等材料，只要有利于后续产生共振以聚集药物颗粒即可。
在一个实施例中，支架型声人工结构可以包括：血管支架基体和薄膜筒，其中，薄膜筒连接在血管支架基体上，如图3a和3b所示，薄膜筒041上设置有多个均匀分布的微孔0411。工作时，薄膜筒041被扩张后也贴附在血管内壁，均匀分布的微孔0411共振聚集药物颗粒。
具体实施时，微孔的截面可为任意形状，图3a中显示的圆形，图3b中显示的矩形，但不局限于圆形和矩形，还可以是三角形等，薄膜可由单一材料或者多种材料复合而成。
具体实施时，微孔的排列方式可以是周期排列、准周期排列、缺陷排列。周期排列可以是一维线排列，二维正方排列、三角排列、六角排列；准周期排列可以是一维准周期和二维准周期排列；缺陷排列可以是一维周期排列中植入一个或多个非相同结构，二维周期排列中植入一个或多个非相同结构。
通过上述可知，共振单元杆可以自身构成网状结构，扩张后的截面状态如图6或图7所示；也可以连接在现有的血管支架基体上，扩张后共振单元杆的截面状态也如图6或图7所示；也可以是薄膜筒连接在血管支架基体上；或者还可以利用激光刻蚀技术在血管支架基体上的预留薄膜区域雕刻微孔等结构。
具体实施时，支架型声人工结构可以是：在医用血管支架上涂覆一层软材料，在直径上做些精确设计即可，加载外超声，即可吸附微粒；或者是在医用血管支架的部分位置上镶嵌声人工结构圆柱(上述实心杆、空心杆或层状杆)或者薄膜筒等，加载外超声，声人工结构圆柱(上述实心杆、空心杆或层状杆)或者薄膜筒即可吸附药物微粒。
在一个实施例中，支架型声人工结构可以为生物兼容材料制成的支架型声人工结构。
具体实施时，支架型声人工结构由生物兼容材料制成，生物兼容材料在人体内无不良反应，与人体血液和组织相容，不会引起凝血、溶血现象，活体组织不会发生炎症、排拒、致癌等现象。
在一个实施例中，支架型声人工结构可以为可降解聚合物材料制成的支架型声人工结构。
在一个实施例中，本发明实施例中的软材料具备药物负载缓释作用，这样可以利于提高药物的生物利用度。
具体实施时，支架型声人工结构采用可降解聚合物材料的目的是：如果支架型声人工结构安装在狭窄的血管内，可降解聚合物材料的支架型声人工结构可以不取出来，局部用药后可以自动降解。但是，后续在使用过程中要调节超声电子装置的入射频率，因为材料降解，直径和性能就会随之改变。
在本发明实施例中，软材料的含义是：软材料的横波速度小于水或血液的纵波速度；硬材料的含义是：硬材料的横波速度大于水或血液的纵波速度。
下面再对本发明实施例中的超声电子装置02进行介绍。
在一个实施例中，超声电子装置可以包括：
信号发生器，用于产生任意波形(包含正弦连续)信号；
功率放大器，用于将任意波形信号放大，获得放大的任意波形信号；
超声换能器，用于在放大的任意波形信号激励下产生超声波。
具体实施时，超声电子装置02工作时，信号发生器产生的特定信号经功率放大器放大后，激励超声换能器发射超声波。
具体实施时，信号发生器的发射任意波形信号可以是宽频脉冲信号，连续正弦信号，或是脉冲正弦信号，其中信号的频谱范围包含声人工结构的共振频率。信号发生器可以是可编程信号发生器(AFG3021，Tectronix)，功率放大器可以是50dB的线性功率放大器(325LA，ENI)。信号发生器产生任意波形信号，任意波形经功率放大器后激励超声换能器产生超声波。
下面对本发明实施例中两种主要结构的超声换能器进行介绍如下。
第一种结构：单探头结构，即上述超声换能器可以包括：
第一探头，用于在体外发射超声波激励支架型声人工结构表面产生局域强场，即用于操控药物微粒，该第一探头的中心频率为2.5MHz。
具体实施时，由于在本发明一个实施例中，支架型声人工结构04采用PLGA实心杆，其直径为0.1毫米，理论预测其产生的局域场强的工作频率为2.578MHz，因此，在本发明一个实施例中，超声换能器的第一探头的中心频率采用2.5MHz，这样可以使得超声换能器发射支架型声人工结构04的工作频率的超声波，进而保证后续对药物颗粒的良好聚集。
具体实施时，所述超声换能器可以为单阵元超声换能器。单阵元超声换能器的中心频率为2.5MHz，当然，还可以使用其它类型的超声换能器，只要保证其中心频率在2.5MHz左右，可以发射支架型声人工结构04的工作频率的超声波即可。
超声换能器还可以是以下装置中任一种：单阵元超声换能器，相控阵超声换能器，线阵超声换能器，凸阵超声换能器，叉指换能器，气体基质压电换能器、CMUT(电容式微加工超声换能器)，只要满足可以产生发射支架型声人工结构04工作频率的超声波，使得支架型声人工结构04对药物颗粒的精确操控聚集即可。
第二种结构：双探头结构，即该超声换能器除了包括上述第一探头，还可以包括：
第二探头，用于在体外提供实现血管及支架型声人工结构超声成像的频率，即用于实现成像，其中心频率可以根据血管及支架型声人工结构尺度获得准确超声影像确定。
具体实施时，所述超声换能器还设计了第二探头，该第二探头可以发射体表血管超声成像频率，该频率适用于体表血管超声成像，利于足够清晰地成像，便于定位支架型声人工结构。
具体实施时，上述超声换能器可以为：双模超声换能器。当然，在本发明实施例中，还可以使用其它类型的超声换能器，只要可以实现双探头工作即可。
接着，对本发明实施例中的支架型声人工结构体内输送装置06进行介绍。
图4a、4b和4c是本发明实施例中支架型声人工结构体内输送装置的结构示意图；其中，图4a为外鞘管的结构示意图，图4b为导管的结构示意图，图4c为外鞘管、导管、扩张器和支架型声人工结构的安装及工作状态结构示意图。
在一个实施例中，如图4a、4b和4c所示，支架型声人工结构体内输送装置06可以包括：
外鞘管061；支架型声人工结构预装在外鞘管061中；
导管062，与外鞘管061连接，用于将扩张器063输送到目标病灶部位的血管内；
扩张器063，设置在导管063外，用于在到达目标病灶的血管内时，将外鞘管061推出的支架型声人工结构04扩张，贴附在血管内壁。
具体实施时，扩张器063可以是球囊，导管062可以是球囊导管，支架型声人工结构04被预装在外鞘管061中，支架型声人工结构04设置在球囊外。工作时，导管062到达血管内的感兴趣区域(目标病灶处)时，外鞘管061推出支架型声人工结构04和球囊，然后，球囊充气使支架型声人工结构04扩张，紧贴在血管壁上。安装完成后，撤出导管062，完成支架型声人工结构04的释放过程。
基于同一发明构思，本发明实施例中还提供了一种上述体内定点给药装置的工作方法，如下面的实施例所述。由于体内定点给药装置的工作方法解决问题的原理与体内定点给药装置相似，因此体内定点给药装置的工作方法的实施可以参见体内定点给药装置的实施，重复之处不再赘述。以下所使用的，术语“单元”或者“模块”可以实现预定功能的软件和/或硬件的组合。尽管以下实施例所描述的装置较佳地以软件来实现，但是硬件，或者软件和硬件的组合的实现也是可能并被构想的。
图16是本发明实施例中体内定点给药装置的工作方法的一种流程示意图，如图16所示，该工作方法包括如下步骤：
步骤101：支架型声人工结构体内输送装置将所述支架型声人工结构输送至目标病灶的血管内，并将所述支架型声人工结构扩张，贴附在所述血管的内壁；
步骤102：超声电子装置在体外发射超声波激励支架型声人工结构表面产生局域强场；
步骤103：预装在所述支架型声人工结构体内输送装置内的支架型声人工结构，在被输送至目标病灶的血管内时，利用所述局域强场，将注入血管内的药物颗粒聚集在所述血管的内壁。
本发明实施例中体内定点给药装置，工作时，支架型声人工结构体内输送装置06将支架型声人工结构04输送至目标病灶的血管内，并将支架型声人工结构04扩张，贴附在血管的内壁；超声电子装置02在体外发射超声波激励支架型声人工结构产生局域强场；支架型声人工结构04利用局域强场，在被输送至目标病灶的血管内时，利用局域强场，将注入血管内的药物颗粒聚集在血管的内壁。
下面结合图5、6和7，对本发明实施例提供的定点给药装置的工作过程进行介绍，以说明本发明如何实施。
首先，要对支架型声人工结构04的工作频率进行确定。以支架型声人工结构的共振单元042为PLGA实心杆为例进行说明。根据PLGA实心杆的直径、材料参数，理论预测并实验测量其表面产生局域场模式的超声工作频率。实验工作可以将支架型声人工结 构放在水中，通过测量透射频谱获得共振频率。本具体实施方案中，PLGA微杆直径为0.1毫米，经过试验后，理论预测其产生局域模式的工作频率为2.578MHz。
其次，对支架型声人工结构在体聚集药物颗粒的过程进行介绍，如图5、6和7所示。将支架型声人工结构04通过支架型声人工结构体内输送装置06植入血管中，并在血管内注入药物颗粒07，在体外利用超声电子装置02发射超声波激发支架型声人工结构04的工作频率的超声场，使得支架型声人工结构表面产生局域声场强，从而吸附其周围药物颗粒聚集，将药物颗粒07聚集在血管壁08内壁。
本发明实施例提供的定点给药装置已经经过数值模拟验证其可行性，下面结合图8至11说明其结果和有益技术效果。
1)以单个直径为D的PLGA(聚乳酸-羟基乙酸共聚物)圆柱(实心杆)在声场中为例(如图8所示)，通过一个宽频脉冲激励PLGA实心杆；
2)PLGA的频率响应如图9所示，在频率为0.173(c/D)的位置处(c为水中声速，D为圆柱(实心杆)直径)有一个共振极值峰，该频率为共振频率；
3)在共振频率时的声压场强度分布如图10所示，声场局域在杆表面，远离表面，声压衰减；
4)图11为共振频率时，密度为1100kg/m^3，声速为2350m/s粒径为1微米粒子在PLGA实心杆周围的力分布，其中箭头表示受力方向，颜色代表受力强度。该图表明，在外声场作用下，由于PLGA实心杆的共振产生的局域声场，可以使得小微粒(药物颗粒)在PLGA实心杆周围受到吸引力的作用，聚集在PLGA的周围。由于这是PLGA的单体效应，因此，PLGA实心杆组成其他的结构(如支架型声人工结构的网状结构等)不会影响其本身的局域场强(声场)，也不会影响对微粒的操控效果。
另外，通过图12至图15记载的实验结果和有益技术效果，也可以说明本发明实施例提供的定点给药装置已经经过数值模拟验证了其可行性。图12是本发明一个实例中共振单元杆结构为钢包裹橡胶圆柱，在超声波产生的局域场强声场中的示意图；图13是本发明实施例中钢包裹橡胶圆柱在局域场强声场中的透射谱；图14是本发明实施例中钢包裹橡胶圆柱在共振频率时其表面压力场分布；图15是本发明实施例中直径为0.01D的药物颗粒在钢包裹橡胶圆柱共振时受到的声辐射力强度和方向(箭头)分布。
最后，对本发明实施例中涉及到的技术术语和结构等进行补充解释如下：
1)本发明实施例中的声场是可以激励血管内支架型声人工结构共振的任意声场，声场形态不限。
2)支架型声人工结构的材料是一种超声激励下可以产生共振声场的材料，即：声场能量局域在材料表面，在血液等流体中其声场强度随着离表面距离增大成指数衰减，共振单元的单体性质不限于柱状体，可以是实心、空心、多种材料组成的层状结构等，支架型声人工结构可以是表面含微结构、内部含微结构等，只要能在声场激励下产生表面局域共振场即可。
3)产生局域声场的材料包含其他各类结构和材料，其为可以在外声源激励下能够产生可操控微粒声场的材料。
4)操控的微粒(例如药物颗粒)不限于为粒径为0.01D的微粒。
5)操控的微粒和支架型声人工结构的材料可以进行化学或生物修饰，增加其粘附效率和靶向性。
6)本发明实施例提供的技术方案包括但不限于血管内药物聚集，也可扩展到其他环境下，如，利用声人工结构在肿瘤或者皮肤外表面药物聚集，人工结构产生的声场操控聚集微粒等应用。
另外，本发明实施例提供的定点给药装置不限用在狭窄血管内，例如：也可以用于对人体支气管的局部给药，人体直肠的局部给药。
本发明实施例实现了如下技术效果：
本发明实施例利用支架型声人工结构作为产生局域声场的“二次声源”装置，实现对血管内药物颗粒的聚集。本发明实施例包括支架型声人工结构、超声电子装置、支架型声人工结构体内输送装置。与传统血管支架相比，本发明提出的支架型声人工结构可以由血管支架基体和新技术特征共振单元构成，血管支架基体完成传统血管支架的功能，共振单元用于被送入目标病灶血管时，产生局域场操控颗粒；另外，与传统血管支架相比，本发明的新技术特征为需要超声电子装置发射超声波激励支架型声人工结构，以实现药物颗粒的定点聚集给药；与先前基于人工结构的操控技术相比，本发明的新技术特征为需要支架型声人工结构体内输送装置将人工结构安置于血管内，并且本发明实施例提供的支架型声人工结构可以收缩和扩张。
本发明实施例利用植入式支架型声人工结构产生的局域声场在体聚集药物颗粒；利用植入式支架型声人工结构振动产生的声场在体操控比结构小很多的微粒；因此，该技术可以用于实现血管内药物颗粒的靶向递送，也可以用于扩展到利用物体共振产生的局域声场操控微纳米颗粒的聚集、检测等应用。
显然，本领域的技术人员应该明白，上述的本发明实施例的各模块或各步骤可以用 通用的计算装置来实现，它们可以集中在单个的计算装置上，或者分布在多个计算装置所组成的网络上，可选地，它们可以用计算装置可执行的程序代码来实现，从而，可以将它们存储在存储装置中由计算装置来执行，并且在某些情况下，可以以不同于此处的顺序执行所示出或描述的步骤，或者将它们分别制作成各个集成电路模块，或者将它们中的多个模块或步骤制作成单个集成电路模块来实现。这样，本发明实施例不限制于任何特定的硬件和软件结合。
以上所述仅为本发明的优选实施例而已，并不用于限制本发明，对于本领域的技术人员来说，本发明实施例可以有各种更改和变化。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。

Claims (20)

  1. 一种体内定点给药装置，其特征在于，包括：支架型声人工结构、支架型声人工结构体内输送装置和超声电子装置；其中，
    所述支架型声人工结构体内输送装置，用于将所述支架型声人工结构输送至目标病灶的血管内，并将所述支架型声人工结构扩张，贴附在所述血管的内壁；
    所述超声电子装置，用于在体外发射超声波激励支架型声人工结构表面产生局域强场；
    所述支架型声人工结构，预装在所述支架型声人工结构体内输送装置内，用于在被输送至目标病灶的血管内时，利用所述局域强场，将注入血管内的药物颗粒聚集在所述血管的内壁。
  2. 如权利要求1所述的体内定点给药装置，其特征在于，所述支架型声人工结构包括：多个共振单元杆编织成的网状结构；所述共振单元杆的横波速度小于水或血液的纵波速度。
  3. 如权利要求2所述的体内定点给药装置，其特征在于，所述共振单元杆的圆周外直径与所述局域强场的波长的关系为：λ＝πD/n；其中，λ为局域强场的波长，D为共振单元杆的圆周直径，n为大于或等于2的整数。
  4. 如权利要求3所述的体内定点给药装置，其特征在于，所述共振单元杆为层状杆，所述层状杆包括：硬材料杆和涂覆在所述硬材料杆的圆周外表面的软材料层。
  5. 如权利要求3所述的体内定点给药装置，其特征在于，所述共振单元杆为硬材料制成的空心杆。
  6. 如权利要求5所述的体内定点给药装置，其特征在于，所述空心杆的内直径取值范围为：0.005毫米至4.95毫米，所述空心杆的外直径取值范围为：0.01毫米至5毫米。
  7. 如权利要求6所述的体内定点给药装置，其特征在于，所述空心杆的内直径取值为：0.09毫米，所述空心杆的外直径取值为：0.1毫米。
  8. 如权利要求5所述的体内定点给药装置，其特征在于，所述空心杆为不锈钢空心杆。
  9. 如权利要求1所述的体内定点给药装置，其特征在于，所述支架型声人工结构包括：血管支架基体和多个共振单元杆；多个共振单元杆连接在所述血管支架基体上；所述共振单元杆的横波速度小于水或血液的纵波速度。
  10. 如权利要求9所述的体内定点给药装置，其特征在于，所述共振单元杆为软材料制成的实心杆。
  11. 如权利要求10所述的体内定点给药装置，其特征在于，所述实心杆为聚乳酸-羟基乙酸共聚物PLGA实心杆。
  12. 如权利要求1所述的体内定点给药装置，其特征在于，所述支架型声人工结构包括：血管支架基体和薄膜筒，其中，所述薄膜筒连接在所述血管支架基体上，所述薄膜筒上设置有多个均匀分布的微孔。
  13. 如权利要求1所述的体内定点给药装置，其特征在于，所述支架型声人工结构为生物兼容材料制成的支架型声人工结构；或，所述支架型声人工结构为可降解聚合物材料制成的支架型声人工结构。
  14. 如权利要求1所述的体内定点给药装置，其特征在于，所述支架型声人工结构体内输送装置包括：
    外鞘管；所述支架型声人工结构预装在所述外鞘管中；
    导管，与所述外鞘管连接，用于将扩张器输送到目标病灶的血管内；
    扩张器，设置在所述导管外，用于在到达目标病灶的血管内时，将所述外鞘管推出的支架型声人工结构扩张，贴附在所述血管内壁。
  15. 如权利要求1所述的体内定点给药装置，其特征在于，所述超声电子装置包括：
    信号发生器，用于产生任意波形信号；
    功率放大器，用于将所述任意波形信号放大，获得放大的任意波形信号；
    超声换能器，用于在所述放大的任意波形信号激励下产生超声波，且任意波形频率包含支架型声人工结构的共振频率。
  16. 如权利要求15所述的体内定点给药装置，其特征在于，所述超声换能器包括：
    第一探头，用于在体外发射超声波激励支架型声人工结构表面产生局域强场，所述第一模式探头的中心频率为2.5MHz。
  17. 如权利要求16所述的体内定点给药装置，其特征在于，所述超声换能器为单阵元超声换能器。
  18. 如权利要求16所述的体内定点给药装置，其特征在于，所述超声换能器还包括：
    第二探头，用于在体外提供实现血管及支架型声人工结构超声成像的频率。
  19. 如权利要求18所述的体内定点给药装置，其特征在于，所述超声换能器为双模超声换能器。
  20. 一种如权利要求1所述的体内定点给药装置的工作方法，其特征在于，包括：
    支架型声人工结构体内输送装置将所述支架型声人工结构输送至目标病灶的血管内，并将所述支架型声人工结构扩张，贴附在所述血管的内壁；
    超声电子装置在体外发射超声波激励支架型声人工结构表面产生局域强场；
    预装在所述支架型声人工结构体内输送装置内的支架型声人工结构，在被输送至目标病灶的血管内时，利用所述局域强场，将注入血管内的药物颗粒聚集在所述血管的内壁。
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