CN115282411A - Delivery system for delivering drugs into the brain using the nasal olfactory region and method of use thereof - Google Patents
Delivery system for delivering drugs into the brain using the nasal olfactory region and method of use thereof Download PDFInfo
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- CN115282411A CN115282411A CN202210063935.9A CN202210063935A CN115282411A CN 115282411 A CN115282411 A CN 115282411A CN 202210063935 A CN202210063935 A CN 202210063935A CN 115282411 A CN115282411 A CN 115282411A
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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
- A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
- A61M11/005—Sprayers or atomisers specially adapted for therapeutic purposes using ultrasonics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
- A61D7/00—Devices or methods for introducing solid, liquid, or gaseous remedies or other materials into or onto the bodies of animals
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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
- 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
-
- 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
- A61M11/02—Sprayers or atomisers specially adapted for therapeutic purposes operated by air or other gas pressure applied to the liquid or other product to be sprayed or atomised
-
- 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
- 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
- A61M2210/06—Head
- A61M2210/0618—Nose
Abstract
The delivery system of the present invention for delivering drugs into the brain using the sniff region comprises: the special nasal obstruction in district, the nose are smelled and are distinguished subassembly, oral cavity breathing subassembly and coordinator subassembly of dosing, and this conveying system uses the design of integration wearing type to connect into whole with each subassembly, adopts the modularization combination between each subassembly, can dismantle and replace. The delivery system for delivering the medicine into the brain by using the nasal olfactory region overcomes the defects and shortcomings of the existing delivery system, has wide application range of the medicine, quick response, no special operation requirement, no stimulation and pain sensation, is suitable for various patients, and can realize the purpose of safe, efficient, quantitative and long-time medicine nasal delivery.
Description
Technical Field
The present invention relates to a device for nasal administration, and in particular to a delivery system for delivering a drug into the brain using the nasal olfactory region.
Background
The blood brain barrier is the most important bottleneck for the medicine to play a role in treating central diseases, and particularly for biological macromolecular medicines, the blood brain barrier cannot be effectively crossed, so that the brain disease treatment effect cannot be played.
Existing routes of administration, such as oral, intravenous, intramuscular, subcutaneous, etc., are not effective for delivering drugs to the Central Nervous System (CNS) due to the presence of the blood-brain barrier (BBB). In addition, as the dosage of the drug increases, systemic side effects also increase.
The central administration route comprises methods such as lateral ventricle administration (ICV) and direct injection of brain parenchyma, and although the central administration route has good targeting property and can directly deliver the medicament to the injured brain area to play a curative effect, complications such as infection and the like may occur after operation because of the traumatic property of the cranium operation. In addition, the existing central administration route has high cost and heavy economic burden on patients, and the wide application of the existing central administration route is not practical for thousands of encephalopathy patients. Therefore, finding a non-invasive central administration route avoiding the obstruction of the blood brain barrier is the most central problem of the drug in the actual treatment of brain diseases.
Experimental animal researches find that an olfactory nerve pathway of an olfactory region of a nasal cavity is a noninvasive and convenient central administration way, the olfactory nerve pathway bypasses a blood brain barrier to directly deliver the medicine to an injured brain region, and the medicine can be used for treating Alzheimer's disease, parkinson's disease, multiple sclerosis, AIDS and stroke. Although the olfactory nerve path provides a feasible path for the medicine to enter the brain without wound, clinical practice shows that the nasal cavity olfactory region medicine administration is limited by a plurality of physiological factors, and the traditional medicine administration device can not effectively deliver the medicine to the nasal cavity olfactory region part, so that the aim that the medicine enters the brain through the olfactory nerve path can not be realized. Some scholars design a cannula which is directly communicated to the vicinity of the olfactory region of the nasal cavity, but because the pore canal structure in the nasal cavity is bent and complex, the upper nasal passage has a plurality of narrow structures and obvious individual difference, so that the intubation method has a plurality of problems, such as the size specifications of length, angle and the like can not be unified, the strong pain sensation of a patient can be caused, and the intubation method can not be applied to the administration of the olfactory region of the nasal cavity in practice.
In a word, the prior art cannot utilize the nasal olfactory region to achieve the purpose of entering the brain of the medicine. At present, a delivery system for realizing safe, efficient, quantitative and long-time delivery of the medicine to the brain by using the nasal olfactory region is not seen, so that the treatment effect of the medicine on central diseases by using the nasal olfactory region to enter the brain is greatly limited.
Disclosure of Invention
The invention aims to provide a safe, efficient, quantitative and long-time nasal olfactory region drug delivery system, which has wide drug application range, is suitable for various patients, has good compliance and no irritation and pain sensation, and overcomes various defects that the existing delivery system can not effectively utilize olfactory nerve pathways to deliver drugs to the brain.
The delivery system for delivering the medicine into the brain by using the nasal olfactory region has the following advantages different from the existing delivery system for delivering the medicine into the brain through the nose:
1. the safety is high: the medicine does not need to add adhesives with cilia toxicity (inhibiting cilia from falling off caused by cilia swinging), mucosal absorption enhancers with potential safety and other additives, has no influence on the physiological microenvironment and cilia movement of the nasal cavity, has no side effects such as stimulation and the like, and has high safety.
2. Accurate positioning and high drug utilization rate: as shown in fig. 1, the entrance of the upper nasal passage is a narrow and pain sensitive area, and the existing delivery system cannot safely and painlessly deliver the medicine into the upper nasal passage, so that the purpose of the administration of the medicine in the olfactory region of the nasal cavity cannot be realized. The delivery system for delivering the drug into the brain by using the nasal olfactory region does not need to prepare the drug into a special dosage form or use a special carrier; the medicine is only prepared into powder, solution, emulsion and suspension, so that the nasal cavity upper nasal passage can be positioned and efficiently delivered safely and painlessly, the medicine cannot enter the trachea and the lung, and the utilization rate is high.
3. Quick acting: the atomization dispersion technology is applied, so that the particle size of the medicine particles is small, the contact area between the medicine particles and the nasal olfactory region after the medicine particles enter the nasal upper nasal passage is large and is uniformly distributed, the medicine absorption is accelerated to the maximum extent, and the effect taking speed is high.
4. Go up the nasal passage nasal smell district position dwell time long, the nasal smell district passageway income brain effectual is smelled to the nasal: as shown in figures 2 to 4, the nasal respirator adopts the uniquely designed nasal plug special for the snuffing area, the snuffing area drug delivery component, the oral cavity breathing component and the coordinator component, so as to ensure the synchronous proceeding of the oral cavity expiration and the nasal cavity drug delivery. In the process of inhaling the oral cavity by a user, no medicine enters the nasal cavity because the driver of the nasal olfactory region administration component is in a stop state; when a user exhales in the oral cavity, on one hand, a driver of the nasal sniffing region dosing assembly is started through the coordinator assembly, the medicine subjected to atomization treatment is quantitatively conveyed to enter a hollow channel of the nasal plug special for the nasal sniffing region, and the nasal plug special for the nasal sniffing region is specially designed to block the inlets of the middle nasal passage and the lower nasal passage, so that the quantitative medicine subjected to atomization treatment enters the upper nasal passage of the nasal cavity, and on the other hand, the air flow from the oropharynx to the lung is blocked due to the positive pressure of the oral cavity exhalation on the oropharynx, so that the medicine entering the upper nasal passage of the nasal cavity is ensured to be only retained in the upper nasal passage of the nasal cavity and cannot enter the lung through the oropharynx; when the user carries out the oral cavity again and breathes in, the driver of the subassembly of dosing is smelled to the nose on the one hand stops working, and the medicine stops to nasal cavity upper nasal passage transport, and on the other hand has had the medicine in the nasal cavity upper nasal passage because of weak negative pressure state can be distributed more evenly near the nasal cavity upper nasal passage smelling the district. Therefore, the conveying system ensures that the medicine stays and is absorbed at the nasal olfactory region, and the effect of the medicine entering the brain through the nasal olfactory region is obviously improved.
5. The patient does not need special operation requirements, and the applicable crowd is wider: the conveying system is simple and convenient to operate, does not need a patient to master special operation actions, and is also suitable for children, old people, patients with mental retardation, coma and the like.
Drawings
Fig. 1 is a graph of the internal structure of the nasal cavity and the airflow during inhalation.
Fig. 2 is a schematic view of the application position and structure design of the nasal obstruction special for the snuffle area.
Fig. 3 is a schematic view of the structural connection relationship of the nasal olfactory region administration component, the oral cavity breathing component and the coordinator component of the invention.
Fig. 4 is a schematic diagram of an application of the delivery system of the present invention for delivering drugs into the brain using the nasal olfactory region.
Detailed Description
Hereinafter, specific embodiments of the present invention will be described in detail. It should be noted that technical features or combinations of technical features described in the following embodiments should not be considered in isolation, and they may be combined with each other to achieve better technical effects.
As shown in fig. 1 and 2, the delivery system for delivering drugs into the brain using the sniff region of the present invention comprises: the nasal obstruction 10 special for the nasal olfactory region, the nasal olfactory region drug delivery component 20, the oral breathing component 30 and the coordinator component 40; the conveying system for delivering the medicine into the brain by utilizing the sniffing area adopts an integrated wearable design to connect all the components into a whole, and all the components are combined in a modularized way and can be detached and replaced.
The special nasal plug 10 for the nasal olfactory region is made of soft material with good biocompatibility, good elasticity and air tightness, and has a shape structure of a column, a gourd shape, a cone shape or a shape structure adapting to an anatomical structure of a nasal cavity, the special nasal plug 10 for the nasal olfactory region is divided into a top part, a middle part and a tail part, the special nasal plug 10 for the nasal olfactory region comprises a hollow channel 11, and two ends of the hollow channel 11 are respectively opened at the tail part and the top part of the special nasal plug 10 for the nasal olfactory region
The surface of the special nasal plug 10 for the snuff area is provided with an annular bulge, and the bulge is in any one of a circular shape, a semicircular shape, an oval shape, a prismatic shape, a triangular shape, a trapezoidal shape or a wavy shape and is used for fixing the position of the special nasal plug 10 for the snuff area in a nasal cavity and simultaneously plugging the inlets of an external nostril, a middle nasal passage and a lower nasal passage.
The snuff region administration set 20 comprises: a medicine storage 21, a nebulizer 22, a screen recoverer 23, an adjustable quantitative control chamber 24, a driver 25 and a communicating pipe 26. The drug reservoir 21 is used to store a drug; the nebulizer 22 is used to disperse the drug in the drug reservoir 21 into small particles or droplets. The mesh recovery device 23 is used to trap and recover drug particles or droplets having a particle size above a predetermined range. The adjustable quantitative control chamber 24 is not only used for controlling the dosage of the medicine given each time, but also used for controlling the medicine not to be diffused to the area outside the upper nasal passage of the nasal cavity due to overlarge volume after entering the upper nasal passage of the nasal cavity. The driver 25 is used for conveying the atomized medicine in the adjustable quantitative control chamber 24 to the hollow channel 11 of the nasal obstruction 10 special for the nasal olfactory region. The communicating tube 26 is used for communicating the drug reservoir 21, the atomizer 22, the adjustable quantitative control room 24, the driver 25 and the nasal obstruction 10 special for the nasal and olfactory region.
The atomizer 22 disperses the drug in the drug reservoir 21 into particles or droplets having a particle size of 1 μm or less by physical action of electrical heating, ultrasonic waves, and high-pressure spraying.
The nebulizer 22 disperses the drug in the drug reservoir to form particles or droplets having a particle size of 200 nm or less using 1-10 MHz high intensity ultrasound.
The oral breathing assembly 30 includes: a mouth adapter 31, a mouth interface tube 32, an inhalation inlet 33 and an exhalation outlet 34.
The coordinator assembly 40 is connected between the nasal and olfactory region drug delivery assembly 20 and the oral cavity breathing assembly 30, and is used for regulating and controlling the driver 25 of the nasal and olfactory region drug delivery assembly 20 to be started when the oral cavity exhales, so as to deliver the drug in the adjustable quantitative control chamber 24 to the nasal and olfactory region special nasal plug.
A method of using a delivery system for delivering a drug into the brain using the nasal olfactory region, comprising the steps of:
(1) The volume of the adjustable quantitative control chamber 24 is adjusted according to different age groups of a user, the nasal obstruction 10 special for the nasal sniffing area, which is connected with the nasal sniffing area administration component 20, is plugged into the nasal cavities at two sides of the user, and the position is adjusted until the air outlet of the nasal cavity is completely plugged after the hollow channel 11 of the nasal obstruction 10 special for the nasal sniffing area is sealed;
(2) The oral breathing assembly 30 is fixed on the mouth of a user to ensure that no gas overflows from the oral breathing assembly 30 when the mouth is used for inhaling and exhaling;
(3) The user keeps a static state, takes a posture of side head, head up or lying, inhales air through the oral breathing component 30, the driver 25 of the nasal and olfactory region administration component 20 is in a static state in the air suction process, and no medicine enters the nasal cavity of the user;
(4) The user slowly exhales, starts the coordinator component 40 in the exhalation process, starts the driver 25 of the nasal olfactory region drug delivery component 20, and delivers the atomized drug in the adjustable quantitative control chamber 24 to the hollow channel 11 of the nasal plug 10 special for the nasal olfactory region, so as to enter the nasal passage on the nasal cavity of the user;
(5) And (5) circulating the steps (3) and (4) to finish the delivery of the medicine to the nasal olfactory region.
Example 1 test grouping of delivery systems for drug delivery into the brain using the nasal olfactory region
The delivery system of the present invention for delivering a drug into the brain using the nasal olfactory region comprises: the special nasal obstruction in district, the district's subassembly of dosing, oral cavity breathing subassembly and coordinator subassembly are smelled to nose, and this conveying system uses the design of integration wearing type to connect into whole with each subassembly, is applied to following test.
Test object(s): the sannen goat (saanen goat) has the nasal cavity structure closest to that of human, so that the sannen goat is taken as an experimental animal subject, male and female are not limited, and each group comprises 3 animals: 1 Saaner goat in the ages of 3-4, 1 in the ages of 7-8 and 1 in the ages of 11-13 respectively represent a young, an adult and an old.
The test method comprises the following steps: the method is characterized in that green fluorescent protein is used as a representative drug, 1mL of green fluorescent protein aqueous solution (100 mu g/mL) is prepared for drug administration, the green fluorescent protein aqueous solution is divided into an experimental group and a control group according to the design of table 1, the position and the volume of the nasal passage on the nasal cavity of an animal are detected through images, a nasal plug special for a snuff area with a proper size is selected, and the volume of an adjustable quantitative control room is adjusted. The body of the animal is in a minus 30-degree body position (the head is slightly lower) after anesthesia, the drug is administrated according to the application method of a conveying system for delivering the drug into the brain by using a nasal olfactory region, and the body position is kept for 10min and then the animal revives after the drug administration is finished. Experimental groups were administered according to the design of table 1 using the delivery system of the present invention for delivering drugs into the brain using the nasal olfactory region, and control groups were administered according to the design of table 1 while referring to experimental groups.
Table 1 test grouping of delivery systems for delivering drugs into the brain using the sniff region
Note: means having noThe feature or structure; * Indicating that the set-up or parameter has changed significantly from the experimental group. Interpretation of ultrasound conditions in the table: high intensity ultrasound (1): the ultrasonic wave emission frequency is 2MHz, and the intensity is 0.5W/m 2 The ultrasonic wave of (4); high intensity ultrasound (2): the ultrasonic wave emission frequency is 10MHz, and the intensity is 1W/m 2 The ultrasonic wave of (4); high intensity ultrasound (3): the ultrasonic wave emission frequency is 5MHz, and the intensity is 1.5W/m 2 The ultrasonic wave of (4); low intensity ultrasound (1): the ultrasonic emission frequency is 100KHz, and the intensity is 0.5W/m 2 The ultrasonic waves of (4); low intensity ultrasound (2): the ultrasonic emission frequency is 75KHz, and the intensity is 1W/m 2 The ultrasonic wave of (2).
Example 2 test results of each group
After nasal administration according to the design of table 1, experimental animals were dissected and the degree of retention of each group of drugs in the nasal upper meatus, the concentration of green fluorescent protein in brain tissue, etc. were evaluated.
Retention of drug in nasal passages: the relative retention of the drug in the upper nasal passage was evaluated by the fluorescence intensity of green fluorescent protein in the upper, middle and lower nasal passages.
Detection of green fluorescent protein concentration in brain tissue: the concentration of the green fluorescent protein in each group of brain tissues is detected by a fluorescence detection method, and the brain-entering effect of the green fluorescent protein at 12h, 24h and 48h after administration is compared.
The test results of each group are shown in table 2, the effect of each index in the table is represented by "+" or "-" ("represents that the evaluation index is good or high, and represents that the evaluation index is poor or low), the overall evaluation is given by combining the indexes, the overall evaluation is in percentage, and the higher the score is, the better the representative effect is.
Table 2 test results of a delivery system for delivering drugs into the brain using the nasal olfactory region
The results in table 2 show that the effect of the experimental group on various aspects of the delivery system for delivering the drug into the brain by using the nasal olfactory region is obviously higher than that of the control group, and the experimental group has the advantages of high retention degree of the drug in the nasal passages of the nasal cavity, high brain-entering effect of the green fluorescent protein of 12h, 24h and 48h, and good overall evaluation, wherein the evaluation of the experimental group 4 is best.
Compared with the experimental group, the effect of the control group is poor, the brain-entering effect of the green fluorescent protein of the control groups 3, 4, 6 and 14 is extremely low, the retention degree of the control groups 1, 12 and 13 in the nasal passage is low, and the brain-entering effect of the green fluorescent protein is extremely low.
The results in table 2 prove that any component and parameter in the technical protection scheme of the delivery system for delivering the drug into the brain by using the snuff region are mutually synergistic and indispensable, and the lack of any component and parameter in the technical protection scheme of the invention can have great influence on the effect of the drug into the brain. The conveying system for delivering the medicine into the brain by using the nasal olfactory region has the characteristics of safety, high efficiency and convenient application, and has good application prospect.
The above detailed description is specific to possible embodiments of the invention, and the embodiments are not intended to limit the scope of the invention, and all equivalent implementations or modifications that do not depart from the scope of the invention should be construed as being included within the scope of the invention. In addition, various modifications, additions and substitutions in other forms and details may occur to those skilled in the art within the scope and spirit of the invention as disclosed in the claims. It is understood that various modifications, additions, substitutions and the like can be made without departing from the spirit of the invention as disclosed in the accompanying claims.
Claims (10)
1. A delivery system for delivering a drug into the brain using the nasal olfactory region, said delivery system comprising: the nasal cavity sniffing device comprises nasal plugs, nasal cavity sniffing region dosing assemblies, oral cavity breathing assemblies and a coordinator assembly, wherein the conveying system is integrally connected into a whole by adopting an integrated wearable design, the assemblies are combined in a modularized manner and can be detached and replaced, and the conveying system is used for conveying particles or liquid drops with the particle size of less than 1 micron to the nasal cavity sniffing region.
2. The system as claimed in claim 1, wherein the nasal prong dedicated to nasal olfactory region is made of a soft material with good biocompatibility, elasticity and air tightness, and has a shape of column, gourd, cone or a contour adapted to the anatomical structure of nasal cavity, and the nasal prong dedicated to nasal olfactory region is divided into three parts, i.e., a top part, a middle part and a tail part, and the nasal prong dedicated to nasal olfactory region has a hollow channel therein, and both ends of the hollow channel are open to the tail part and the top part of the nasal prong dedicated to nasal olfactory region.
3. The system as claimed in claim 2, wherein the surface of the nasal prong dedicated to the nasal olfactory region has an annular protrusion with any one of a circular, semicircular, elliptical, prismatic, triangular, trapezoidal or wavy shape for fixing the position of the nasal prong dedicated to the nasal olfactory region in the nasal cavity while blocking the entrance of the external nostril, the middle nasal passage and the lower nasal passage.
4. The system of claim 1, wherein the nasally administered assembly comprises a reservoir, a nebulizer, a mesh retriever, an adjustable dosing chamber, a driver, and a tube.
5. The system for delivery of a drug into the brain using the olfactory region of the nose as claimed in claim 4, wherein the drug reservoir is for storing a drug; the atomizer is used for dispersing the medicament in the medicament storage to form small particles or liquid drops; the screen recoverer is used for intercepting and recovering medicine particles or liquid drops with the particle size above a specified range; the adjustable quantitative control chamber is not only used for controlling the dosage of the medicine given each time, but also used for controlling the medicine not to be diffused to the area outside the upper nasal passage of the nasal cavity due to overlarge volume after entering the upper nasal passage of the nasal cavity; the driver is used for conveying the atomized medicine in the adjustable quantitative control chamber to the hollow channel of the special nasal plug for the nasal olfactory region; the communicating pipe is used for communicating the medicine storage, the atomizer, the adjustable quantitative control room, the driver and the nasal plug special for the nasal olfactory region.
6. The delivery system of claim 5, wherein the nebulizer uses physical effects of electrical heating, ultrasound, and high pressure spray to disperse the drug in the drug reservoir into particles or droplets with a size of less than 1 μm.
7. The system for delivering drugs into the brain using the snuff region according to claim 6, wherein the nebulizer uses 1-10 MHz high intensity ultrasound to disperse the drugs in the drug reservoir into particles or droplets with a size of less than 200 nm.
8. The delivery system for nasally-olving delivery of a drug into the brain according to claim 1, wherein the oral breathing assembly comprises: the oral cavity adapter chamber, oral cavity butt joint pipe, inhale inlet and exhale the export.
9. The system for delivering drugs into the brain by using the snuff region as claimed in claim 1, wherein the coordinator module is connected between the snuff region drug delivery module and the oral cavity breathing module, and is used for controlling the driver of the snuff region drug delivery module to be activated when the oral cavity exhales, so as to deliver the drugs in the adjustable quantitative control chamber into the nasal plug special for the snuff region.
10. A method of using a delivery system for the delivery of a drug into the brain using the nasal olfactory region as claimed in any one of claims 1 to 9, the method comprising the steps of:
(1) The volume of the adjustable quantitative control room is adjusted according to different age groups of a user, the nasal cavity air outlet is completely blocked after the hollow channel of the nasal cavity special nasal plug for the nasal sniffing area, which is connected with the nasal sniffing area administration component, is adjusted to be plugged into the nasal cavities at two sides of the user;
(2) The oral breathing component is fixed on the mouth of a user, so that no gas overflows from the oral breathing component when the mouth is used for inhaling and exhaling;
(3) The user keeps a static state, is in a lateral head, a head-up or lying posture, inhales air through the oral breathing component, the nasal olfactory region administration component driver is in a static state in the air inhaling process, and no medicine enters the nasal cavity of the user;
(4) A user slowly exhales gas, starts the coordinator component in the process of exhaling, starts a driver of the nasal cavity inhalation component, and conveys the atomized medicine in the adjustable quantitative control chamber to a hollow channel of the nasal plug special for the nasal cavity inhalation zone so as to enter the nasal cavity upper nasal passage of the user;
(5) And (5) circulating the steps (3) and (4) to finish the delivery of the medicine to the nasal olfactory region.
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