CN108042888B

CN108042888B - Method and apparatus for preparing superfine particle medicine by atomization

Info

Publication number: CN108042888B
Application number: CN201711392047.7A
Authority: CN
Inventors: 孙永学; 王晓俊逸; 刘雅红; 王勉之
Original assignee: South China Agricultural University
Current assignee: South China Agricultural University
Priority date: 2017-12-21
Filing date: 2017-12-21
Publication date: 2021-03-30
Anticipated expiration: 2037-12-21
Also published as: CN108042888A

Abstract

The invention relates to the field of medicine preparation, in particular to an atomization preparation method and a manufacturing device of an ultrafine particle medicine. The atomization preparation method of the ultrafine particle medicine comprises the following steps: the drug and aerosol carrier are mixed and subjected to ultrasonic atomization after cavitation for at least two times. Compared with the existing method, the method has the advantages of simple operation, large-scale production and low requirement on instruments, and the medicament can be completely changed into particles with the particle size of 1-3 microns through twice cavitation and atomization, so that the administration effect of the medicament is ensured.

Description

Method and apparatus for preparing superfine particle medicine by atomization

Technical Field

The invention relates to the field of medicine preparation, in particular to an atomization preparation method and a manufacturing device of an ultrafine particle medicine.

Background

The Aerosol Delivery Formulation (ADF) is that after the drug is ultrafinely processed into aerosol particles, the surface area is greatly increased, the surface energy is significantly changed, the adhesiveness is enhanced with the increase of the solubility, and the aerosol particles can be directly delivered to the deep lung through the respiration, thereby improving the drug effect and reducing the drug dosage. Researches show that the Particle Size (PS) of the medicine is between 1 and 5 mu m, and the Particle Size Distribution (PSD) has certain requirements. If the particle size is less than 1 mu m, the particles can be suspended in the bronchus to form brownian motion and cannot be directly conveyed into the lung; if the particle size is larger than 5 μm, it is easy to collide with the upper airway wall to form a capillary flow, and the drug is reversely carried into the oral cavity to make it into oral drug. Therefore, not only the ADF needs to have an appropriate average particle diameter but also the PSD is within a small interval and the fine particles are easily dispersed.

The existing common aerosol adopts carbon dioxide as a carrier, so that the cost is high, and the carbon dioxide is easy to inhibit respiration, thereby further influencing the drug effect. In addition, the prior art generally adopts a supercritical fluid technology to prepare ultrafine particles, and when the method cannot carry out durable large-scale processing and obtaining on ultrafine medicine particles, the method cannot be industrialized in a large scale.

Disclosure of Invention

Compared with the existing method, the method has the advantages of simple operation, large-scale production and low instrument requirement, and the medicament can be completely changed into particles with the particle size of 1-3 microns through twice cavitation and atomization, so that the administration effect of the medicament is ensured.

The invention also aims to provide a preparation device for implementing the atomization preparation method of the ultrafine particle medicine, which can quickly cavitate the medicine and further ensure that all particles obtained by preparation have the particle size of 1-3 microns.

The embodiment of the invention is realized by the following steps:

an atomization preparation method of ultrafine particle medicine comprises the following steps: the drug and aerosol carrier are mixed and subjected to ultrasonic atomization after cavitation for at least two times.

A preparation device for implementing the atomization preparation method of the ultrafine particle medicine comprises a mixer for mixing the medicine and the aerosol carrier and carrying out first cavitation, a venturi tube for carrying out second cavitation and an ultrasonic atomizer for carrying out ultrasonic atomization, wherein the mixer, the venturi tube and the ultrasonic atomizer are sequentially connected.

According to the invention, the medicament can be completely changed into particles with the particle size of 1-3 microns through cavitation and atomization for at least two times, so that the administration effect of the medicament is further ensured, the technical problem that carbon dioxide is used as an aerosol carrier to inhibit breathing can be solved by selecting water as the aerosol carrier, and meanwhile, the raw material is more easily obtained, and the production cost is reduced. And the aerosol particles prepared by cavitation and atomization twice can be processed in large batch for a long time compared with the supercritical fluid technology, and are suitable for large-scale industrial application.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.

FIG. 1 is a schematic view of a manufacturing apparatus for an atomized manufacturing method of an ultrafine particulate drug according to a fourth embodiment of the present invention;

FIG. 2 is a schematic structural diagram of a mixer according to a fourth embodiment of the present invention;

FIG. 3 is a schematic structural view of a cavitation nozzle provided in accordance with a fourth embodiment of the present invention;

fig. 4 is a schematic structural diagram of an ultrasonic atomizer according to a fourth embodiment of the present invention.

Icon: 100B-preparation apparatus; 200-a drug addition component; 210-a drug reservoir; 220-a drug delivery tube; 230-a drug restriction valve; 240-drug pressurization pump; 300-an aerosol carrier addition component; 310-an aerosol carrier reservoir; 320-an aerosol carrier delivery tube; 330-aerosol carrier flow-limiting valve; 340-aerosol carrier pressurizing pump; 400-a mixer; 401 — a first inlet; 412-a heating device; 402-a second inlet; 410-a mixer body; 420-an orifice plate assembly; 430-an adjustment assembly; 421-fixed orifice plate; 423-movable orifice plate; 431-threaded rod; 433-adjusting rod; 435-a threaded hole; 405-a first outlet; 500-pressure relief reflux system; 501-pressure gauge; 503-safety valve; 505-a return pipe; 407-a second outlet; 440-a cavitation nozzle; 411-nut; 413-a baffle plate assembly; 413 a-a first fixation plate; 413 b-a second fixation plate; 413 c-a third fixation plate; 413 d-a first movable plate; 413 e-a second flap; 413 f-a third movable plate; 600-a venturi tube; 700-ultrasonic atomizer; 710-an atomizer body; 720-ultrasonic nozzle; 730-an ultrasonic generator; 740-an ultrasonic vibrator; 750-air supply device; 760-atomizing sheet.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. The components of embodiments of the present invention generally described and illustrated in the figures herein may be arranged and designed in a wide variety of different configurations.

Thus, the following detailed description of the embodiments of the present invention, presented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

It should be noted that: like reference numbers and letters refer to like items in the following figures, and thus, once an item is defined in one figure, it need not be further defined and explained in subsequent figures.

In the description of the present invention, it should be noted that the terms "first", "second", and the like are used only for distinguishing the description, and are not intended to indicate or imply relative importance.

Some embodiments of the invention are described in detail below with reference to the accompanying drawings. The embodiments described below and the features of the embodiments can be combined with each other without conflict.

The invention specifically describes an atomization preparation method of ultrafine particle medicine, which comprises the following steps:

the aerosol carrier is water, the existing aerosol carrier usually uses carbon dioxide, but the carbon dioxide has an inhibiting effect on respiration, the cost of the carbon dioxide is relatively high, and the water used as the aerosol carrier can reduce the production cost on one hand and can reduce CO on the other hand₂Has respiratory depression effect on livestock and poultry, and increases the absorption of the medicine by utilizing the respiratory mucosa of the livestock and poultry to improve the medicine effect.

Firstly, mixing an active ingredient with a solvent to obtain a mixed solution, namely a medicament, wherein the adopted active ingredient is a medicament with low or extremely low solubility in ethanol, and water-soluble substances such as cephalo, aminoglycosides and the like in water. The solvent is 65-70% ethanol water solution. That is, the concentration of the active ingredient in the medicament is 40-70mg/mL after the active ingredient is mixed with the solvent.

After the preparation of the medicine is finished, the medicine and the aerosol carrier are mixed, but before the mixing, the aerosol carrier and the medicine are required to be subjected to heat preservation treatment respectively, so that the aerosol carrier and the medicine have higher energy, are convenient to mix uniformly and are convenient to form cavitation. The temperature of the aerosol carrier and the medicine are respectively kept at 30-90 ℃.

Further, mixing the medicine with the aerosol carrier, and performing heat preservation treatment on the mixture of the medicine and the aerosol carrier during mixing, wherein the heat preservation temperature is 30-90 ℃. The heat preservation treatment is carried out in the mixing process, so that the uniform mixing and the first-time cavitation generation are more convenient.

Further, when the medicine is mixed with the aerosol carrier, the convection premixing is carried out in the mixer in a convection mode by adopting different flow rates and flow velocities, so that initial power is provided for the first cavitation, and the cavitation of the mixture is more convenient to occur.

Further, the first cavitation is performed while the drug and the aerosol carrier are mixed. The cavitation of the invention is hydrodynamic cavitation, wherein hydrodynamic cavitation refers to pressure drop generated when fluid passes through a flow limiting area, when the pressure drops below vapor pressure or even negative pressure, gas dissolved in the fluid can be released, meanwhile, the fluid is vaporized to generate a large amount of cavitation bubbles, and when the cavitation bubbles further flow along with the fluid and meet the increase of surrounding pressure, the volume is rapidly reduced until collapse, and cavitation is generated. While the mixture maintains the temperature, increasing the dissolution of the active ingredient and increasing the efficiency of the drug.

Further, the flow ratio of the aerosol carrier and the drug is 0.7-1.3 when the drug and the aerosol carrier are mixed, and the mixing pressure is 10-25 Mpa. By adopting the mixing conditions, the medicine can be ensured to be dissolved in the aerosol carrier as much as possible, and then the formed aerosol is ensured to contain higher medicine content.

The first cavitation can preliminarily obtain the medicine aerosol particles with proper particle size, but 60% of particles can be obtained according to research statistical data and strictly meet the requirements of ADF, therefore, in order to enable the obtained particles to completely meet the requirements of ADF, the second cavitation is carried out in a Venturi tube, the particle size of the prepared particles meets the requirements of ADF, and the drug effect of the particles is further improved.

Then, the particles subjected to cavitation twice are subjected to ultrasonic atomization again to further generate small-molecule aerosol, so that the drug molecules directly enter a respiratory tract or an alveolus through the aerosol to achieve the effect of adjuvant therapy, and aerosol particles with the average particle size of 1-3 mu m are obtained after ultrasonic atomization.

The frequency of ultrasonic atomization is 1.5-3MHz, which can rapidly further reduce the particle size of the particles and improve the particle size distribution.

Because the aerosol carrier is water, the water is easy to settle, so that the medicine can not reach the treatment part, and the treatment effect is reduced. Therefore, in order to solve the technical problem, the aerosol particles are dried after ultrasonic atomization, and part of water is removed, so that the aerosol particles have enough power to run to a treatment part, and the targeting property of the aerosol particles is improved. However, the drying may be performed according to the environment, that is, the drying may not be performed in a region where the ambient temperature is high, and in this case, the moisture content in the aerosol particles is appropriate and the aerosol particles are less likely to settle. Preferably, the water content in the aerosol is controlled to be 30-40%, so that aerosol particles do not settle before entering a diseased part, and can quickly settle after reaching the diseased part, and the drug effect is improved.

First embodiment

The invention provides an atomization preparation method of ultrafine particle medicine, which comprises the following steps:

mixing the active ingredient with a solvent to obtain a mixed solution, i.e. a medicine, wherein the solvent is 70% ethanol water solution, and the concentration of the active ingredient in the medicine is 40 mg/mL.

The distribution keeps the temperature of the aerosol carrier and the medicine at 30 ℃.

Mixing the medicine and the aerosol carrier, and performing heat preservation treatment on the mixture of the medicine and the aerosol carrier during mixing, wherein the heat preservation temperature is 30 ℃. When the medicine and the aerosol carrier are mixed, the flow ratio of the aerosol carrier to the medicine is 0.7, and the mixing pressure is 10 Mpa.

Then, the first cavitation, the second cavitation and the ultrasonic atomization are carried out in sequence, and the frequency of the ultrasonic atomization is 1.5 MHz. At this time, the moisture content in the aerosol was 30%.

Second embodiment

The atomization preparation method of the ultrafine particle medicine provided by the invention is basically the same as the atomization preparation method of the ultrafine particle medicine provided by the first embodiment, and the difference is that the operation conditions are changed.

The solvent is 65% ethanol water solution, the concentration of active ingredient in the medicine is 70mg/mL, the temperature for heat preservation is 90 deg.C, the flow ratio of aerosol carrier and medicine is 1.3, and the mixing pressure is 25 Mpa. The frequency of ultrasonic atomization was 3 MHz. And then drying is carried out, and the moisture content in the aerosol is 40%.

Third embodiment

The solvent is 68% ethanol water solution, the concentration of active ingredient in the medicine is 50mg/mL, the temperature for heat preservation is 50 ℃, the flow ratio of the aerosol carrier and the medicine is 1, the mixing pressure is 20Mpa, the frequency of ultrasonic atomization is 2 MHz, and the water content in the aerosol is 35%.

Fourth embodiment

Referring to fig. 1, the present embodiment provides a manufacturing apparatus 100B for implementing the aerosol manufacturing method of ultrafine particulate medicine of the first embodiment, which includes a medicine adding assembly 200, and the medicine adding assembly 200 transports the medicine. The drug adding assembly 200 includes a drug reservoir 210, a drug delivery tube 220, a drug restriction valve 230, and a drug pressurization pump 240, and the drug reservoir 210, the drug pressurization pump 240, and the drug restriction valve 230 are all connected to the drug delivery tube 220.

The production device 100B further comprises an aerosol carrier addition assembly 300, which transports the aerosol. The aerosol carrier adding assembly 300 comprises an aerosol carrier storage tank 310, an aerosol carrier delivery pipe 320, an aerosol carrier flow limiting valve 330 and an aerosol carrier pressurizing pump 340, wherein the aerosol carrier storage tank 310, the aerosol carrier pressurizing pump 340 and the aerosol carrier flow limiting valve 330 are all connected with the aerosol carrier delivery pipe 320.

The manufacturing apparatus 100B further includes a mixer 400, and the mixer 400 is for mixing the drug and the aerosol carrier and generating the first cavitation. The mixer 400 is T-shaped and has 4 ports, wherein the mixer 400 includes a first inlet 401 and a second inlet 402, and the drug adding assembly 200 and the aerosol carrier adding assembly 300 are respectively communicated with the first inlet 401 and the second inlet 402. That is, the first inlet 401 and the second inlet 402 are respectively connected with the drug reservoir 210 and the aerosol carrier reservoir 310 through the drug delivery tube 220 and the aerosol carrier delivery tube 320 in a one-to-one correspondence.

Referring to fig. 1 and 2, the mixer 400 includes a mixer body 410, an orifice plate assembly 420 for cavitation of the drug and aerosol carrier, and an adjustment assembly 430 for adjusting the size of the orifice plate assembly 420, the orifice plate assembly 420 being disposed in the mixer body 410 and connected to the mixer body, the orifice plate assembly 420 and the mixer body 410 being connected to the adjustment assembly 430. By adjusting the size of the inner hole of the orifice plate assembly 420, a first cavitation occurs therein, resulting in drug particles having a certain particle size.

Further, orifice plate subassembly 420 includes fixed orifice plate 421 and activity orifice plate 423, and fixed orifice plate 421 and activity orifice plate 423 all set up in blender body 410, and fixed orifice plate 421 and blender body 410 fixed connection, activity orifice plate 423 and blender body 410 swing joint, and activity orifice plate 423 is connected with adjustment subassembly 430. The size of the overlapped holes of the movable orifice plate 423 and the fixed orifice plate 421 is then adjusted by adjusting the position of the movable orifice plate 423, thereby realizing the adjustment of the cavitation effect.

Specifically, the adjusting assembly 430 includes a threaded rod 431 and an adjusting rod 433, the threaded rod 431 is connected with the movable orifice plate 423, the adjusting rod 433 is disposed outside the mixer body 410, one end of the threaded rod 431 is connected with the adjusting rod 433, the other end of the threaded rod 431 is in threaded connection with the mixer body 410, that is, a threaded hole 435 is disposed in the mixer body 410, and one end of the threaded rod 431 is disposed in the threaded hole 435 and in threaded connection with the threaded hole 435. After the user manually screws the adjusting rod 433, the threaded rod 431 is driven to rotate, then the threaded rod 431 is driven to move in the threaded hole 435, then the movable orifice plate 423 is driven to move, then the relative position between the movable orifice plate 423 and the fixed orifice plate 421 is adjusted, and then the adjustment of the size of the cavitation aperture is realized.

The mixer 400 further includes a first outlet 405, the preparation apparatus 100B further includes a pressure relief reflux system 500, and two ends of the pressure relief reflux system 500 are respectively communicated with the first outlet 405 and the aerosol carrier addition assembly 300. The pressure relief reflux system 500 is provided to avoid the over-high pressure of the cavitator, release the over-high pressure in the mixer 400, ensure the safety of the mixer 400, and improve the safety of the whole preparation apparatus 100B. The decompression backflow system 500 is communicated with the aerosol carrier adding assembly 300, the redundant liquid medicine in the mixer 400 is led back to the aerosol carrier adding assembly 300, and then the aerosol carrier adding assembly 300 is communicated.

Referring to fig. 1 again, the pressure relief backflow system 500 includes a pressure gauge 501, a safety valve 503 and a backflow pipe 505, two ends of the backflow pipe 505 are respectively communicated with the first outlet 405 and the aerosol carrier storage tank 310, and the pressure gauge 501 and the safety valve 503 are both disposed on the backflow pipe 505 and connected to the backflow pipe 505. When the pressure indicated on the pressure gauge 501 exceeds a predetermined value, the safety valve 503 is opened to introduce the excessive amount of the liquid medicine in the mixer 400 into the aerosol carrier tank 310.

Further, the mixer 400 further includes a second outlet 407, and the second outlet 407 is connected to the venturi 600, so that the aerosol particles obtained through mixing and cavitation enter the venturi 600. Preferably, a cavitation nozzle 440 with an adjustable aperture size is provided at the second outlet 407 to allow the ejection of a stream of gas containing the drug to amplify the cavitation effect occurring within the mixer 400 to allow for adequate preconditioning of the drug.

Referring to fig. 3, the cavitation nozzle 440 includes a nut 411 and a baffle assembly 413, the nut 411 is in threaded connection with the second outlet 407 of the mixer 400, the nut 411 is connected with the baffle assembly 413, and then when the nut 411 is screwed with respect to the mixer body 410, the baffle assembly 413 is driven to displace, and then the caliber of the nozzle is changed.

Specifically, the baffle plate assembly 413 includes a first fixed plate 413a, a second fixed plate 413b, a third fixed plate 413c, a first movable plate 413d, a second movable plate 413e and a third movable plate 413f, the first fixed plate 413a, the second fixed plate 413b, the third fixed plate 413c, the first movable plate 413d, the second movable plate 413e and the third movable plate 413f are all fixedly connected to the nut 411, the first fixed plate 413a, the second fixed plate 413b and the third fixed plate 413c are respectively hinged to the first movable plate 413d, the second movable plate 413e and the third movable plate 413f in a one-to-one correspondence manner, and the first movable plate 413d, the second movable plate 413e and the third movable plate 413f are disposed outside the nut 411 in a three-fork structure.

When the nut 411 moves in a direction away from the mixer body 410, the first fixing plate 413a, the second fixing plate 413b and the third fixing plate 413c are driven to move in the direction away from the mixer body 410, so that the aperture enclosed among the first movable plate 413d, the second movable plate 413e and the third movable plate 413f is enlarged. When the nut 411 moves towards the mixer body 410, the first fixing plate 413a, the second fixing plate 413b and the third fixing plate 413c are driven to move towards the mixer body 410, so that the aperture defined between the first movable plate 413d, the second movable plate 413e and the third movable plate 413f is reduced. The inventors have found that the larger the aspect ratio (L/D) of the cavitation nozzle 440, the finer the particles that settle out; when the L/D is reduced, the length-diameter ratio of the precipitation product is increased to form a threadlike shape; the nozzle aperture increases and the diameter of the filament formed increases, thus, when the present invention is optimized for cavitation nozzles 440 having an aspect ratio of 15.

Further, the preparation apparatus 100B further comprises a heating device 412, the mixer body 410 is placed in the heating device 412 for heating, and the heating device 412 is used for heating and insulating the mixture in the mixer 400.

Further, the preparation apparatus 100B further includes a venturi tube 600 for performing second cavitation, the venturi tube 600 is connected to the mixer body 410, and further cavitates the aerosol particles subjected to the first cavitation, so that the particle size of the aerosol particles meets the requirement and the particle size distribution is more uniform.

Further, referring to fig. 4, the preparation apparatus 100B further includes an ultrasonic atomizer 700, which is used for performing ultrasonic atomization on the twice cavitated aerosol particles, so that the drug molecules can enter the respiratory tract or the alveoli in an aerosol manner, and then the therapeutic effect is achieved. The ultrasonic atomizer 700 is connected to the venturi 600.

The ultrasonic atomizer 700 comprises an atomizer body 710, an ultrasonic nozzle 720, an ultrasonic generator 730 and an ultrasonic vibrator 740, wherein the ultrasonic nozzle 720, the ultrasonic generator 730 and the ultrasonic vibrator 740 are all arranged in the atomizer body 710, the ultrasonic generator 730 is connected with the ultrasonic vibrator 740, the ultrasonic vibrator 740 is connected with the ultrasonic nozzle 720, and the ultrasonic nozzle 720 is connected with the venturi tube 600. In the aerosol granule transmission in the venturi 600 reaches ultrasonic nozzle 720, ultrasonic generator 730 produces or transmits the supersound and then passes to ultrasonic vibrator 740, then drives ultrasonic vibrator 740 vibration, then atomizes the aerosol granule in ultrasonic nozzle 720, and in the nozzle sprays to atomizer body 710 with the back, then outside transport atomizer body 710, atomizes.

Further, the ultrasonic atomizer 700 further includes an air supply device 750 for blowing the atomized aerosol particles in the atomizer body 710 out of the atomizer body 710 to prevent the atomized aerosol particles from settling in the atomizer body 710. Specifically, the air supply device 750 is disposed in the atomizer body 710 and connected to the top of the atomizer body 710.

Further, the ultrasonic atomizer 700 further includes an atomizing sheet 760, and the atomizing sheet 760 is disposed inside the atomizer body 710 and connected to the bottom of the atomizer body 710, so that aerosol particles settled on the bottom of the atomizer body 710 can be atomized again and then sent out of the atomizer body 710 by the air supply device 750.

Preferably, the atomizing sheet 760 has an arc-shaped structure, so that the liquefied chemical can be completely gathered within the range of the atomizing sheet 760 by gravity, and further processed into aerosol mist by the atomizing sheet 760, and discharged together with the gas mist sprayed from the atomizing nozzle. The arc projects away from the atomizer body 710.

Comparative example 1: aerosol particles were prepared using the aerosol production method of ultrafine particulate medicament of the first embodiment, except that the aerosol carrier was carbon dioxide.

Comparative example 2: aerosol particles were prepared using the aerosol production method of ultrafine particulate drug of the first example, except that only the first cavitation was performed.

Comparative example 3: aerosol particles were prepared by the atomization preparation method of the ultrafine drug of the first example, except that ultrasonic atomization was not performed.

Comparative example 4: aerosol particles were prepared using the aerosol production method of ultrafine particulate drug of the first embodiment, except that the drug, aerosol carrier and mixture of the two were not incubated.

Experimental example 1

The aerosol particles prepared in example 1 and comparative examples 1 to 4 were subjected to particle size detection (average particle size) and particle size distribution (particle size range with percentage of 90% or more), and were detected by dynamic light scattering experiments, and data of the dynamic light scattering experiments were analyzed by the CONTIN algorithm, which is specifically referred to the CONTIN algorithm and its application in measuring particle size distribution of microgel particles, cheng hua and liu wei. The specific test results are shown in table 1.

TABLE 1 particle size detection

	Average particle diameter (μm)	Particle size distribution
			Experimental example 1	2.5	1-3
Comparative example 1	3	1-4
			Comparative example 2	6	1-8
Comparative example 3	5	1-6
			Comparative example 4	4.5	1-5

As can be seen from Table 1, the particles of the aerosol completely do not meet the requirements only by carrying out cavitation once, and the composite requirements of partial particles are met without heat preservation and heating or atomization, but the particle size is too large, and the particle size distribution is also large, so that the drug absorption is not facilitated.

In conclusion, the invention ensures that the medicine can be completely changed into particles with the particle size of 1-3 microns through cavitation and atomization for at least two times, thereby ensuring the administration effect of the medicine, solving the technical problem that carbon dioxide is taken as an aerosol carrier to inhibit respiration by selecting water as the aerosol carrier, and simultaneously, the raw material is easier to obtain, and the production cost is reduced. And the aerosol particles prepared by cavitation and atomization twice can be processed in large batch for a long time compared with the supercritical fluid technology, and are suitable for large-scale industrial application.

The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. An atomization preparation method of ultrafine particle medicine is characterized by comprising the following steps: mixing the drug and the aerosol carrier, performing cavitation for at least two times, and then performing ultrasonic atomization; wherein, the first cavitation is carried out while the medicine and the aerosol carrier are mixed, the aerosol carrier is water, and aerosol particles formed after ultrasonic atomization are 1-3 μm; when the medicine is mixed with the aerosol carrier, the medicine is subjected to convective premixing in a mixer in an opposite-impact mode by adopting different flow rates and flow velocities.

2. The process of claim 1, wherein the first of the two cavitations is performed at a temperature of 30-90 ℃ while maintaining the temperature of the mixture of the drug and the aerosol carrier.

3. The process of claim 1, wherein the drying is carried out after the ultrasonic atomization.

4. The aerosol manufacturing method of ultrafine particulate drugs according to claim 1, wherein the drugs are mixed solutions obtained by mixing active ingredients with solvents, and the aerosol carriers and the drugs are separately subjected to heat preservation before mixing.

5. A manufacturing apparatus for carrying out a method for manufacturing an ultrafine particulate drug according to claim 1, comprising a mixer for mixing the drug and the aerosol carrier and carrying out the first cavitation, a venturi tube for carrying out the second cavitation, and an ultrasonic atomizer for carrying out the ultrasonic atomization, the mixer, the venturi tube, and the ultrasonic atomizer being connected in this order,

the preparation device comprises a cavitation nozzle, and the cavitation nozzle is arranged between the mixer and the Venturi tube and is in threaded connection with the mixer;

the cavitation nozzle comprises a nut and a baffle plate assembly, the nut is in threaded connection with the mixer, and the nut is connected with the baffle plate assembly;

the baffle plate assembly comprises a first fixed plate, a second fixed plate, a third fixed plate, a first movable plate, a second movable plate and a third movable plate, the first fixed plate, the second fixed plate, the third fixed plate, the first movable plate, the second movable plate and the third movable plate are fixedly connected with a nut, the first fixed plate, the second fixed plate and the third fixed plate are respectively hinged with the first movable plate, the second movable plate and the third movable plate in a one-to-one correspondence mode, and the first movable plate, the second movable plate and the third movable plate are arranged outside the nut in a three-fork-shaped structure.

6. A manufacturing apparatus as set forth in claim 5 wherein said mixer includes a mixer body, an orifice plate assembly for effecting cavitation of said medicament and said aerosol carrier, and an adjustment assembly for adjusting the size of said orifice plate assembly, said orifice plate assembly being disposed within and coupled to said mixer body, said orifice plate assembly and said mixer body both being coupled to said adjustment assembly, said mixer body being coupled to said venturi.

7. The manufacturing apparatus as set forth in claim 6 wherein said orifice assembly includes a fixed orifice and a movable orifice, both of said fixed orifice and said movable orifice being disposed within said mixer body, said fixed orifice being fixedly connected to said mixer body, said movable orifice being movably connected to said mixer body, said movable orifice being connected to said regulating assembly.

8. The manufacturing apparatus of claim 5, further comprising a drug addition component and an aerosol carrier addition component, the mixer comprising a first inlet and a second inlet; the drug adding component and the aerosol carrier adding component are respectively communicated with the first inlet and the second inlet.

9. The manufacturing device according to claim 8, further comprising a pressure relief reflux system, wherein two ends of the pressure relief reflux system are respectively communicated with the first outlet of the mixer and the aerosol carrier addition component.

10. The manufacturing apparatus according to claim 5, wherein the ultrasonic atomizer comprises an atomizer body, an ultrasonic nozzle, an ultrasonic generator and an ultrasonic vibrator, the ultrasonic nozzle, the ultrasonic generator and the ultrasonic vibrator are all disposed in the atomizer body, the ultrasonic generator is connected with the ultrasonic vibrator, the ultrasonic vibrator is connected with the ultrasonic nozzle, and the ultrasonic nozzle is connected with the venturi tube.