CN108926759A - A kind of atomizing piece nuclear pore membrane and preparation method thereof - Google Patents
A kind of atomizing piece nuclear pore membrane and preparation method thereof Download PDFInfo
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- CN108926759A CN108926759A CN201710366080.6A CN201710366080A CN108926759A CN 108926759 A CN108926759 A CN 108926759A CN 201710366080 A CN201710366080 A CN 201710366080A CN 108926759 A CN108926759 A CN 108926759A
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- 210000004492 nuclear pore Anatomy 0.000 title claims abstract description 71
- 238000002360 preparation method Methods 0.000 title claims description 5
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- 239000000919 ceramic Substances 0.000 claims description 39
- 239000000853 adhesive Substances 0.000 claims description 18
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- 239000007788 liquid Substances 0.000 claims description 16
- 229910001220 stainless steel Inorganic materials 0.000 claims description 15
- 239000010935 stainless steel Substances 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 12
- 239000000758 substrate Substances 0.000 claims description 11
- 239000004411 aluminium Substances 0.000 claims description 10
- 229910052782 aluminium Inorganic materials 0.000 claims description 10
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000000020 Nitrocellulose Substances 0.000 claims description 7
- FJWGYAHXMCUOOM-QHOUIDNNSA-N [(2s,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6s)-4,5-dinitrooxy-2-(nitrooxymethyl)-6-[(2r,3r,4s,5r,6s)-4,5,6-trinitrooxy-2-(nitrooxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-3,5-dinitrooxy-6-(nitrooxymethyl)oxan-4-yl] nitrate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O)O[C@H]1[C@@H]([C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@@H](CO[N+]([O-])=O)O1)O[N+]([O-])=O)CO[N+](=O)[O-])[C@@H]1[C@@H](CO[N+]([O-])=O)O[C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O FJWGYAHXMCUOOM-QHOUIDNNSA-N 0.000 claims description 7
- 229920001220 nitrocellulos Polymers 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 229920003223 poly(pyromellitimide-1,4-diphenyl ether) Polymers 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 4
- 238000007738 vacuum evaporation Methods 0.000 claims description 4
- 229920006289 polycarbonate film Polymers 0.000 claims description 3
- 229920006267 polyester film Polymers 0.000 claims description 3
- 238000004140 cleaning Methods 0.000 claims description 2
- 239000013078 crystal Substances 0.000 claims description 2
- 239000005357 flat glass Substances 0.000 claims 1
- 239000004575 stone Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 29
- 229940079593 drug Drugs 0.000 abstract description 21
- 239000011148 porous material Substances 0.000 abstract description 11
- 238000000889 atomisation Methods 0.000 abstract description 9
- 230000008021 deposition Effects 0.000 abstract description 8
- 230000005484 gravity Effects 0.000 abstract description 3
- 238000004062 sedimentation Methods 0.000 abstract description 3
- 206010035664 Pneumonia Diseases 0.000 abstract description 2
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 238000002604 ultrasonography Methods 0.000 abstract description 2
- 239000000443 aerosol Substances 0.000 description 56
- 238000009826 distribution Methods 0.000 description 11
- 210000004072 lung Anatomy 0.000 description 11
- 238000002626 targeted therapy Methods 0.000 description 9
- 230000003902 lesion Effects 0.000 description 7
- 239000008249 pharmaceutical aerosol Substances 0.000 description 7
- 210000002345 respiratory system Anatomy 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 210000000621 bronchi Anatomy 0.000 description 5
- 210000003123 bronchiole Anatomy 0.000 description 5
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- 238000005516 engineering process Methods 0.000 description 4
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- 238000001704 evaporation Methods 0.000 description 2
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- 230000008685 targeting Effects 0.000 description 2
- IVNOJHSSOXLLSM-UHFFFAOYSA-N 2-pyran-2-ylidenepyran-3-carboximidamide Chemical compound NC(=N)C1=CC=COC1=C1OC=CC=C1 IVNOJHSSOXLLSM-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 241000158526 Nasalis Species 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
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- 230000007812 deficiency Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- YGANSGVIUGARFR-UHFFFAOYSA-N dipotassium dioxosilane oxo(oxoalumanyloxy)alumane oxygen(2-) Chemical compound [O--].[K+].[K+].O=[Si]=O.O=[Al]O[Al]=O YGANSGVIUGARFR-UHFFFAOYSA-N 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 238000005213 imbibition Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002664 inhalation therapy Methods 0.000 description 1
- 238000000608 laser ablation Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052627 muscovite Inorganic materials 0.000 description 1
- 238000002663 nebulization Methods 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
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Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B17/00—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups
- B05B17/04—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods
- B05B17/06—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations
- B05B17/0607—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers
- B05B17/0638—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers spray being produced by discharging the liquid or other fluent material through a plate comprising a plurality of orifices
- B05B17/0646—Vibrating plates, i.e. plates being directly subjected to the vibrations, e.g. having a piezoelectric transducer attached thereto
-
- 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
- A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
- A61M11/005—Sprayers or atomisers specially adapted for therapeutic purposes using ultrasonics
-
- 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
- A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
- A61M11/001—Particle size control
- A61M11/003—Particle size control by passing the aerosol trough sieves or filters
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D29/00—Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups B01D24/00 - B01D27/00; Filtering elements therefor
- B01D29/01—Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups B01D24/00 - B01D27/00; Filtering elements therefor with flat filtering elements
- B01D29/05—Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups B01D24/00 - B01D27/00; Filtering elements therefor with flat filtering elements supported
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B37/00—Methods or apparatus for laminating, e.g. by curing or by ultrasonic bonding
- B32B37/12—Methods or apparatus for laminating, e.g. by curing or by ultrasonic bonding characterised by using adhesives
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B38/00—Ancillary operations in connection with laminating processes
- B32B38/0004—Cutting, tearing or severing, e.g. bursting; Cutter details
Abstract
The present invention provides atomizing piece nuclear pore membranes, including micropore area and fixed area；The micropore area is located at centre, there is tapered micro holes；The fixed area is located at the periphery in micropore area.The beneficial effects of the invention are as follows：1) particle scale is by pore size control, the alveolar so that most of drug particle can go directly, and by gravity sedimentation and disperse deposition in lung inflammation position；2) nuclear pore membrane pass can be adjusted arbitrarily, realize passive target therapeutic purposes；3) nuclear pore membrane hole density control atomization dosage, keeps drug dose adjustable, and is possibly realized in the administration of short time large dosage；3) it avoids avoiding shake piece temperature excessively high using hyperfrequency ultrasound, some drugs being made to fail；5) high-power ultrasonic wave is not needed, that is, can reach large dosage of administration.
Description
Technical field
The invention belongs to medicinal atomized treatment technology fields, in particular to nuclear pore membrane ultrasonic atomizatio chip technology field.
Background technique
The purpose of medicinal atomized treatment is that the drug of delivering therapeutic agents amount reaches targeting moiety.For pulmonary lesion patient,
Atomized medicine introducing can reach higher local drug concentration compared with other administration modes, reduce systemic adverse reactions.Mist in recent years
Change constantly bringing forth new ideas and improving for sucking technology, improves drug output and suction efficiency, increase drug pulmonary concentration.
Nebulae inhalation refers mainly to aerosol therapy.So-called aerosol, which refers to, is suspended in the air small solid or liquid
Body particle.Therefore fog inhalation therapy is that drug (solution or powder) is dispersed into small droplet or micro- with the device being atomized
Grain, is suspended in it in gas, and enters respiratory tract and intrapulmonary, reaches clean air flue, humidifying airway, local treatment and whole body are controlled
The purpose for the treatment of.
Aerosol size is to determine one of the principal element of nebulae inhalation effect, usually straight with aerodynamic force mass median
Diameter (MMAD) indicates.Aerosol is in dynamic suspension, and due to evaporating or absorbing hydrone, aerosol can be combined with each other and deposit.
When the aerosol of water imbibition is in wet environment, moisture is easily absorbed and volume increases, to influence aerosol in respiratory tract
Deposition.Aerosol has 3 in the main mechanism that respiratory system deposits：Collision, gravitational settling and disperse.The aerosol being relatively large in diameter
(10 μm of MMAD >) is usually filtered in the upper respiratory tract or pharynx nasalis due to inertial collision；It is exhaled under 5~10 μm of aerosol is reachable
Inhale road proximal end；1~5 μm of aerosol is then transmitted to peripheral airways and alveolar through air flue, wherein 3~5 μm of aerosol easily deposits
In bronchus or conductive airways；The aerosol that 3 μm of < is by gravity sedimentation in respiratory bronchiole and alveolar；0.5 μm of <
Aerosol then pass through Brownian movement disperse to tracheal wall or alveolar after deposit, but part can be breathed out with expiratory air.
Current main nebulization equipment blast atomizer, ultrasonic atomizer and vibration sieve pore atomizer.
Blast atomizer driving force is compressed air or oxygen, and according to Venturi effect, high-speed flow passes through pore nozzle
When, negative pressure is generated around it and the liquid in atomizer is involved in and is ground into the aerosol to differ in size.Influence its performance
And the factor of drug conveying is complicated, including：(1) air-flow and pressure driven generates gas if certain driving air-flow or bleed pressure are low
The diameter of colloidal sol is easily larger.(2) dose in tank.(3) density of gas is driven：Drive the density of gas low, air-flow conveying is in layer
Stream, is easy to aerosol delivery.(4) humidity and temperature：With the evaporation of moisture when nebulae inhalation, the decline of aerosol temperature can increase
The viscosity of solubilization liquid, to reduce drug output.In addition, the aerosol particle diameter distribution that jet atomization generates is wide, it is heavy in lung
Product rate only about 10%, is extremely difficult to ideal lung treatment effect, and volume is big, noise is big.
Ultrasonic atomizatio is that the ultrasonic wave generated using ultrasonic transducer is propagated by atomizing medium, is formed at gas-liquid interface
Capillary wave destroys fluid molecule active force due to ultrasonic cavitation, deviates to form droplet from liquid surface, thus
Liquid is atomized as aerosol state.The function of jet velocity that ultrasonic atomizatio generates is low, and the initial velocity of drop is almost
Zero, the flow of required carrier gas is small, is easy to produce the tiny drop stream of high concentration, is conducive to transport and deposit.With pneumatic nebulizer
It compares, ultrasonic atomizer has the advantages that many tempting.One is aerosol generation rate is unrelated with carrier gas flux on energy converter,
Thus aerosol generate rate and carrier gas can independent choice, so as to ICP Performance optimization；The second is gained aerosol quantity is compared with gas
Dynamic atomizer is about 10 times big；The third is the mean size of aerosol particle is related with the frequency of ultrasonic wave, increasing frequency be can produce
Thinner droplet, thus analyte transport efficiency will be higher；The fourth is can be used for the atomization of high salt solution or suspension.Although
There is above-mentioned advantage, still, the aerosol partial size that ultrasonic atomizatio generates will reach 5~10 μm, about~MHz high-frequency vibration is needed,
Incident is high power consumption and localized hyperthermia, destroys drug speciality.Currently, ultrasonic atomizatio pharmaceutical aerosol is in pulmonary deposition ratio
It is also only 2%~12%, cannot effectively treat lower respiratory illness
Sieve pore atomizer is shaken by electric current as power, is shaken liquid and is passed through tiny sieve pore generation aerosol, sieve pore
Diameter determine aerosol size.Sieve pore atomizer atomization efficiency height is shaken, residual volume is few (0.1~0.5ml).However, by
Completed in current capillary processing mainly by laser ablation or chemistry etch techniques, micropore quantity, shape, aperture parameters adjustment with
And the selection of atomization sheet material is very limited, so that there are following defects for such atomizer：1) condensation aerosol is dense
It spends low；2) aerosol partial size is not small enough, keeps the aerosol volume ratio of through alveolar not high；3) aerosol particle diameter distribution is wide, SR
Value is about 8~12.When these defects cause to treat pulmonary disease using this kind of atomizer, there are 1) drug effective rates of utilization
It is low；2) administration of short time large dosage is difficult；3) it not can be carried out targeted therapy, when such as pulmonary infection, drug can be fed simultaneously simultaneously
It is deposited on lung, tracheae and bronchus.
Summary of the invention
In order to solve a series of deficiencies existing for current product, the present inventor proposes side of the invention by many experiments
Case.
Firstly, the present invention provides a kind of atomizing piece nuclear pore membrane, including micropore area and fixed area, wherein micropore position
In centre, fixed area is located at micropore area periphery, and there is the micropore of single cone or bipyramid in micropore area.
Further, aperture d=1~12 μm of micropore, D=3~60 μm；The density 3 × 10 of micropore3~2 × 106/cm2；
Thickness L=8~200 μm of micropore.
Secondly, the present invention also provides a kind of atomizing pieces, including：PZT (piezoelectric transducer) and atomizing piece nuclear pore membrane, wherein
PZT (piezoelectric transducer) includes boring area and external entity area, the fixed area phase in external entity area and atomizing piece nuclear pore membrane
Connection, boring area are corresponding with the micropore area of atomizing piece nuclear pore membrane.
Further, PZT (piezoelectric transducer) includes piezoelectric ceramic piece energy converter, piezoelectric single crystal energy converter.
Further, piezoelectric ceramic piece energy converter includes piezoelectric ceramic piece, metal layer, and metal layer is in piezoelectric ceramics on piece
Face, for generating one end of ultrasonic circuit needed for connecting；It is connected below piezoelectric ceramic piece with the circuit other end；And paste atomization
The fixed area of piece nuclear pore membrane.
Further, the shape of piezoelectric ceramic piece is annular, rectangular, polygon.
Further, the aperture of single cone hole is respectively d and D, and Aperture side is connect with piezoelectric ceramics face or Aperture side and pressure
There is ring stainless steel piece between electroceramics face.
Further, the material of nuclear pore membrane be polyester BOPET, polycarbonate, polyimides Kapton, muscovite or
Glass.
Further, atomizing piece generates 50KHz~200KHz by circuit control, and driving piezoelectric ceramics generates high-frequency vibration,
The nuclear pore membrane being attached on piezoelectric ceramics carries out high-frequency vibration therewith, and makes the medicinal atomized medium in micropore in gas-liquid interface
Place forms capillary wave, destroys fluid molecule active force due to ultrasonic cavitation, deviates to form mist from liquid surface
Drop sprays so that liquid is atomized into aerosol state from the Aperture side of nuclear pore membrane.The partial size upper limit of aerosol is by core micropore
Membrane aperture d control；Aerosol particle diameter limit is controlled by nuclear pore membrane parameter D, L and ultrasonic frequency；Aerosol dose, i.e., singly
The aerosol quantity that the position time generates is determined by hole density, micropore area area and circuit power.
Third, invention additionally provides a kind of preparation methods of atomizing piece nuclear pore membrane, including
(1) it is formed with the high energy particle irradiation that energy is 10~50MeV/u with a thickness of 10~270 μm of nuclear pore membrane raw materials
Track density is 3 × 103~2 × 106/cm2Latent track film；
(2) at 20~80 DEG C, Latent track film is immersed in soak to specified conditions；
(3) Latent track film is taken out, is cleaned, atomizing piece nuclear pore membrane is made in drying.
Further, high energy particle includes U particle, Pb particle, Kr particle.
Further, nuclear pore membrane raw material includes polycarbonate film, polyester film, Kapton, polyimides
Film, quartz glass plate.
Further, before Latent track film being immersed in soak, 0.5~1 μm first is printed in the one side (face A) of Latent track film
Cellulose nitrate layer.
Further, after printing cellulose nitrate layer, the aluminium layer that 0.01~0.1 μm of vacuum evaporation.
Further, it is deposited after aluminium layer and has the Film laminated of adhesive.
Further, soak includes the sodium hydroxide solution of 5mol/l, the potassium hydroxide of 8mol/l and 1% potassium permanganate
Solution, the liquor potassic permanganate of 6mol/l, 48%HF solution.
Further, specified conditions include that 10~40 minutes or aluminium layer completely disappear.
Further, compound band glue film is torn into removal before cleaning.
4th, present invention provides a kind of preparation methods of atomizing piece, including
1) atomizing piece cuts into the identical diaphragm with PZT (piezoelectric transducer) periphery with nuclear pore membrane；
2) 200 μm of stainless steel substrates are cut into it is identical as PZT (piezoelectric transducer) shape, size, and in the one side of stainless steel substrates
Coat one layer of adhesive；
3) there is the one side of adhesive compound the Aperture side of atomizing piece nuclear pore membrane and stainless steel；
4) another side of stainless steel substrates is bonded on PZT (piezoelectric transducer).
The beneficial effects of the invention are as follows：1) drug granule scale is by pore size control, because nuclear pore membrane aperture is small, thus is atomized
The aerosol partial size of generation is small, the alveolar so that most of drug particle can go directly, and passes through gravity sedimentation and disperse deposition
In lung inflammation position；2) nuclear pore membrane pass can be adjusted arbitrarily, thus can produce the very narrow atomization of aerosol particle diameter distribution
Piece realizes passive target therapeutic purposes；3) nuclear pore membrane hole density and micropore area area control are atomized dosage：Unit time generates
Particulate quantity by the adjusting of pore density can be achieved it is a wide range of adjust, keep drug dose adjustable, and make the short time
Large dosage administration is possibly realized；3) it avoids avoiding shake piece temperature excessively high using hyperfrequency ultrasound, some drugs being made to fail；5) not
High-power ultrasonic wave is needed, that is, can reach large dosage of administration.
For the benefit of patient increases effective inhalation dose, and the intrapulmonary for the atomization medicine that atomizing piece provided by the invention generates is heavy
Product rate (50%~90%) is obviously increased compared with traditional technology (10%~15%), and passes through the distribution of optimization aerosol size and control
Aerosol size realizes lung's targeting atomization conveying, so that aerosol deposition in peripheral airways and alveolar or is only deposited at
Aerosol is directly served only on lesions position by tracheae or bronchus, greatly improves the service efficiency of drug.
Detailed description of the invention
Fig. 1 nuclear pore membrane figure.
The mono- cone nuclear pore membrane sectional side view of Fig. 2.
Fig. 3 bipyramid hole nuclear pore membrane figure.
Fig. 4 has the atomizing piece figure of stainless steel substrates.
The aerosol partial size and its distribution map of 1 micron of single cone hole film atomizing piece of Fig. 5.
The aerosol partial size and its distribution map of 3.3 microns of single cone hole film atomizing pieces of Fig. 6.
The aerosol partial size and its distribution map of 8.0 microns of single cone hole film atomizing pieces of Fig. 7.
The aerosol partial size and its distribution map of 12.0 μm of single cone hole film atomizing pieces of Fig. 8.
The aerosol partial size and its distribution map of 5.0 μm of single cone hole film atomizing pieces of Fig. 9.
Figure 10 vibrates sieve pore atomizer commodity condensation aerosol grain size distribution.
The atomizer SR value comparison diagram of Figure 11 different parameters nuclear pore membrane production.
Specific embodiment
Embodiment 1
1) the Kr particle-irradiation that energy is 10MeV/u is with a thickness of 10 μm of polycarbonate films, is formed Track density for 2 ×
106/cm2Latent track film；
2) the one side of Latent track film (face A) print one layer of cellulose nitrate layer, 0.5 μm of print thickness range；
3) in the certain thickness aluminium layer of the face A vacuum evaporation of Latent track film, 0.01~0.1 μm of thickness range；
4) by the face A of Latent track film and after having the Film laminated of adhesive, 70 in the sodium hydroxide solution of 5mol/L
It DEG C impregnates, until when aluminium layer completely disappears, takes out Latent track film, compound band glue film is torn into removal；
5) it cleans, drying is made with a thickness of 8 μm, d=1 μm, D=3Mm, ρ=2 × 106/cm2Single cone hole type core
Microporous barrier；
6) nuclear pore membrane of manufactured single cone hole type is cut into film identical with ring-shaped piezo ceramic outside diameter size
Piece；
7) one is cut into and the identical annulus of ring-shaped piezo ceramic shape size with a thickness of 200 μm of stainless steel substrates
Piece, and one layer of adhesive is coated in the one side of stainless steel substrates；
8) there is the one side of adhesive compound the Aperture side of the nuclear pore membrane of single cone hole type and stainless steel, such as Fig. 4 structure；
9) another side of the stainless steel substrates with nuclear pore membrane is bonded on piezoelectric ceramics, and is made and can be used for lung deep
The atomizing piece of lesion tissue targeted therapy；
10) by the two sides connection electrode of piezoelectric ceramics, the circuit of electrode both ends connection output high frequency waves, by medicine thing liquid
Body contacts nuclear pore membrane, powers on, pharmaceutical aerosol as shown in Figure 5 can be ejected in the small bore end in nuclear pore membrane.
From figure 5 it can be seen that all 2 μm of the particulate diameter being atomized through nuclear pore membrane atomizing piece hereinafter,
For 60% or more particle diameter between 0.5~1.5 μm, such aerosol will be deposited on respiratory bronchiole and alveolar；
Nearly 40% particle is diameter between 0.25~0.5 μm, all through alveolars, and part disperse is deposited on alveolar, partially with
Breathing exhalation human body；There is no aerosol deposition in the upper respiratory tracts such as tracheae and oral cavity, can achieve drug lung targeted therapy mesh
's.
Embodiment 2
1) energy is the Kr particle-irradiation of 10MeV/u with a thickness of 20 μm of polyester films, and forming Track density is 2 × 105/cm2
Latent track film；
2) the one side of Latent track film (face A) print one layer of cellulose nitrate layer, 1 μm of print thickness range；
3) in the certain thickness aluminium layer of the face A vacuum evaporation of Latent track film, 0.01~0.1 μm of thickness range；
4) by the face A of Latent track film and after having the Film laminated of adhesive, in potassium hydroxide+mass concentration of 8mol/L
65 DEG C of immersions in 1% liquor potassic permanganate, observe the variation of aluminium coated on film, when aluminium layer completely disappears, take out Latent track film,
Compound band glue film is torn into removal；
5) it cleans, drying is made with a thickness of 15 μm, d=3 μm, D=10 μm, ρ=2 × 105/cm2Single cone hole type
Nuclear pore membrane；
6) manufactured nuclear pore membrane 2 is cut into diaphragm identical with ring-shaped piezo ceramic outside diameter size；
7) one is cut into and the identical annulus of ring-shaped piezo ceramic shape size with a thickness of 200 μm of stainless steel substrates
Piece, and one layer of adhesive is coated in the one side of stainless steel substrates；
8) there is the one side of adhesive compound the Aperture side of nuclear pore membrane and stainless steel, such as Fig. 4 structure；
9) another side of the stainless steel substrates with nuclear pore membrane is bonded on piezoelectric ceramics, that is, is made and can be used for lung deep
The atomizing piece of lesion tissue targeted therapy；
10) by the two sides connection electrode of piezoelectric ceramics, the circuit of electrode both ends connection output high frequency waves, by medicine thing liquid
Body contacts nuclear pore membrane, powers on, can eject pharmaceutical aerosol as shown in FIG. 6 in the small bore end in nuclear pore membrane.
From fig. 6 it can be seen that all 2 μm of the particulate diameter being atomized through nuclear pore membrane atomizing piece hereinafter,
For 80% or more particle diameter between 0.5~1.5 μm, such aerosol will be deposited on respiratory bronchiole and alveolar；
Nearly 20% particle is diameter between 0.25~0.5 μm, all through alveolars, and part disperse is deposited on alveolar, partially with
Breathing exhalation human body；There is no aerosol deposition in the upper respiratory tracts such as tracheae and oral cavity, can achieve drug lung targeted therapy mesh
's.
Embodiment 3
1) the Kr particle-irradiation that energy is 10MeV/u is with a thickness of 40 μm of Kaptons, is formed Track density for 8 ×
104/cm2Latent track film；
2) the one side of Latent track film (face A) print one layer of cellulose nitrate layer, 0.5 μm of print thickness range；
3) by the face A of Latent track film and after having the Film laminated of adhesive, 80 in the liquor potassic permanganate of 6mol/L
It DEG C impregnates 30 minutes, takes out Latent track film, compound band glue film is torn into removal；
4) it cleans, drying is made with a thickness of 32 μm, d=8 μm, D=15 μm, ρ=8 × 104/cm2Single cone hole type
Nuclear pore membrane；
5) manufactured nuclear pore membrane 2 is cut into diaphragm identical with ring-shaped piezo ceramic outside diameter size；
6) in the circular adhesive of the Aperture side coating of film one, annulus outer diameter is identical as piezoelectric ceramics outer diameter, and internal diameter is greater than
Piezoelectric ceramics internal radius 1mm；
7) nuclear pore membrane and piezoelectric ceramics that have adhesive is compound, the structure such as Fig. 1 is formed, that is, being made can be used for lung
The atomizing piece of deep tissue lesion targeted therapy；
8) by the two sides connection electrode of piezoelectric ceramics, the circuit of electrode both ends connection output high frequency waves, by medicine thing liquid
Body contacts nuclear pore membrane, powers on, pharmaceutical aerosol as shown in Figure 7 can be ejected in the small bore end in nuclear pore membrane.
From fig. 6 it can be seen that all 8 microns of the particulate diameter being atomized through nuclear pore membrane atomizing piece hereinafter,
For 25.6% particle diameter between 0.5~1.0 μm, such aerosol will be deposited on alveolar；Nearly 10% particle is diameter
Between 0.25~0.5 μm, all go directly alveolar, and part disperse is deposited on alveolar, partially breathes out human body with breathing；19.4%
Particle diameter between 1.0~3.0 μm, such aerosol will be deposited on bronchiole and alveolar；16% particle diameter
Between 3.0~5.0 μm, it is deposited on bronchus；For 31.2% particle diameter between 5.0~8.0 μm, such aerosol will
Bronchus, bronchiole and alveolar will be deposited on by being deposited on tracheae i.e. and be more than 68% pharmaceutical aerosol, without aerosol deposition
In oral cavity, drug respiratory tract targeted therapy purpose can achieve.
Embodiment 4
1) the Pb particle-irradiation that energy is 50MeV/u is with a thickness of 270 μm of Kaptons, is formed Track density for 3 ×
103/cm2Latent track film；
2) by Latent track film, 20 DEG C immersion 40 minutes, taking-up Latent track film are cleaned, are dried in volumetric concentration 48%HF solution
It is dry, that is, it is made with a thickness of 200 μm, d=12 μm, D=60 μm, ρ=3 × 103/cm2Bipyramid pass nuclear pore membrane；
3) manufactured nuclear pore membrane 2 is cut into diaphragm identical with ring-shaped piezo ceramic outside diameter size；
4) in the circular adhesive of the one side coating of film one, annulus outer diameter is identical as piezoelectric ceramics outer diameter, and internal diameter is greater than pressure
Electroceramics internal radius 1mm；
5) nuclear pore membrane and piezoelectric ceramics that have adhesive is compound, the structure such as Fig. 1 is formed, that is, being made can be used for lung
The atomizing piece of deep tissue lesion targeted therapy；
6) by the two sides connection electrode of piezoelectric ceramics, the circuit of electrode both ends connection output high frequency waves, by medicine thing liquid
Body contacts nuclear pore membrane, powers on, pharmaceutical aerosol as shown in Figure 8 can be ejected in the small bore end in nuclear pore membrane.
Embodiment 5
1) energy is the U particle-irradiation of 38MeV/u with a thickness of 130 μm of quartz glass plates, and forming Track density is 3 × 104/
cm2Latent track film；
8) the one side of Latent track film (face A) print one layer of cellulose nitrate layer, 0.5 μm of print thickness range；
9) face A of Latent track film is impregnated 10 points for 20 DEG C in 40%HF solution with after the Film laminated with adhesive
Clock takes out Latent track film, and compound band glue film is torn removal；
10) it cleans, drying is made with a thickness of 100 μm, d=5 μm, D=25 μm, ρ=3 × 104/cm2Single cone hole type
Nuclear pore membrane；
11) manufactured nuclear pore membrane 2 is cut into diaphragm identical with ring-shaped piezo ceramic outside diameter size；
12) in the circular adhesive of the Aperture side coating of film one, annulus outer diameter is identical as piezoelectric ceramics outer diameter, and internal diameter is greater than
Piezoelectric ceramics internal radius 1mm；
13) nuclear pore membrane and piezoelectric ceramics that have adhesive is compound, the structure such as Fig. 1 is formed, that is, being made can be used for
The atomizing piece of lung deep tissue lesion targeted therapy；
14) by the two sides connection electrode of piezoelectric ceramics, the circuit of electrode both ends connection output high frequency waves, by medicine thing liquid
Body contacts nuclear pore membrane, powers on, pharmaceutical aerosol as shown in Figure 9 can be ejected in the small bore end in nuclear pore membrane.
The atomizer for shaking sieve pore atomizer and nuclear pore membrane production of comparison external commercialization at present, nuclear pore membrane production
The SR value (2~2.9) of aerosol extinction that generates of atomizer be below vibration screen atomizer SR value (8~12), illustrate to produce
Raw particulate particle diameter distribution is narrow.
Claims (13)
1. a kind of atomizing piece nuclear pore membrane, which is characterized in that including micropore area and fixed area；
The micropore area is located at centre, there is tapered micro holes；
The fixed area is located at the periphery in micropore area.
2. atomizing piece nuclear pore membrane according to claim 1, which is characterized in that the taper is single taper or bipyramid
Shape.
3. atomizing piece nuclear pore membrane according to claim 1, which is characterized in that
The aperture of the micropore is d=1~12 μm, D=3~60 μm；
The density 3 × 10 of the micropore3~2 × 106/cm2；
8~200 μm of the thickness of the micropore.
4. a kind of atomizing piece, which is characterized in that including：PZT (piezoelectric transducer) and atomizing piece nuclear pore membrane,
The PZT (piezoelectric transducer) includes boring area and external entity area, external entity area and atomizing piece nuclear pore membrane
Fixed area be connected, boring area is corresponding with the micropore area of atomizing piece nuclear pore membrane.
5. atomizing piece according to claim 4, which is characterized in that
The PZT (piezoelectric transducer) includes piezoelectric ceramic piece energy converter, piezoelectric single crystal energy converter.
6. atomizing piece according to claim 5, which is characterized in that the piezoelectric ceramic piece energy converter includes piezoelectric ceramics
Piece, metal layer,
The metal layer is on piezoelectric ceramic piece, for generating one end of ultrasonic circuit needed for connecting；Piezoelectric ceramic piece
It is connected below with the circuit other end；And paste the fixed area of atomizing piece nuclear pore membrane.
7. atomizing piece according to claim 6, which is characterized in that the shape of the piezoelectric ceramic piece be it is annular, rectangular,
Polygon.
8. atomizing piece according to claim 6, which is characterized in that the aperture of the single cone hole of the atomizing piece nuclear pore membrane
There are stainless steel substrates to be connected between face and the connection of piezoelectric ceramics face or Aperture side and piezoelectric ceramics face.
9. a kind of preparation method of atomizing piece nuclear pore membrane, which is characterized in that including：
(1) track is formed with a thickness of 10~270 μm of nuclear pore membrane raw materials with the high energy particle irradiation that energy is 10~50MeV/u
Density is 3 × 103~2 × 106/cm2Latent track film；
(2) at 20~80 DEG C, Latent track film is immersed in soak to specified conditions；
(3) Latent track film is taken out, is cleaned, atomizing piece nuclear pore membrane is made in drying；
The high energy particle includes U particle, Pb particle, Kr particle；
The nuclear pore membrane raw material includes polycarbonate film, polyester film, Kapton, Kapton, stone
English sheet glass.
10. according to the method described in claim 9, it is characterized in that, it is described Latent track film is immersed in soak before,
0.5~1 μm of cellulose nitrate layer is printed in the one side (face A) of Latent track film,
The aluminium layer that 0.01~0.1 μm of vacuum evaporation,
With the Film laminated for having adhesive.
11. according to the method described in claim 9, it is characterized in that, the soak include 5mol/l sodium hydroxide it is molten
Liquid, the potassium hydroxide of 8mol/l and mass concentration are 1% liquor potassic permanganate, the liquor potassic permanganate of 6mol/l, volumetric concentration
48%HF solution.
12. according to the method described in claim 9, it is characterized in that, the specified conditions include 10~40 minutes or aluminium
Layer completely disappears.
13. according to the method described in claim 9, it is characterized in that, removing compound film before the cleaning.
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| CN110141738A (en) * | 2019-05-10 | 2019-08-20 | 首都医科大学附属北京儿童医院 | Eye drops atomizing therapeutic device suitable for infant |
| CN110193442A (en) * | 2019-04-24 | 2019-09-03 | 深圳市尚进电子科技有限公司 | A kind of mesh-type ultrasonic atomization piece and manufacturing process |
| CN110324985A (en) * | 2019-07-10 | 2019-10-11 | 深圳市尚进电子科技有限公司 | Ultrasonic atomization piece production technology |
| WO2023051499A1 (en) * | 2021-09-28 | 2023-04-06 | 健康元药业集团股份有限公司 | Drug assembly containing formoterol fumarate inhalation solution and use thereof |
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