Nasal cavity soft fog administration device and method and application

Abstract

The invention discloses a nasal cavity soft mist drug delivery device and method and application, and relates to the technical field of drug delivery, and the device comprises a drug delivery main body and a mist spray adapter. The method comprises the following steps: assembling the administration main body and the spray adapter; placing the assembled device horizontally or upside down, and inserting the top end of the spray adapter into the nasal cavity; a cavity filled with air is formed in the extrusion horizontal or inverted administration body, medicine generates soft mist through a micropore chip arranged in the spray adapter, and the soft mist enters the nasal cavity to be delivered and administered. The nasal cavity soft fog administration device can be applied to rhinitis, allergy, vomiting and nervous centralis related indications. According to the invention, a preservative-free single-dose sterile solution or suspension produced by blowing, filling and sealing can be efficiently and quickly atomized into soft fog moving slowly, and atomized liquid drops are small in particle size and uniform in distribution, and can be more diffused and deposited in all intranasal areas.

Description

Technical Field

[0001] The present invention relates to the technical field of drug delivery, and in particular to a nasal soft mist drug delivery device, method and application. Background Art

[0002] The human nasal drug delivery area can be roughly divided into five parts, namely area 1 olfactory area, area 2 middle turbinate, area 3 inferior turbinate, area 4 nasopharyngeal area and area 5 nasal vestibule. For many years, due to the local drug delivery mechanism and the influence of the particle size and speed of the drug sprayed by the nasal drug delivery device, the action area of ​​nasal spray is mainly concentrated in the nasal vestibule, and the treatment field of nasal spray is mainly concentrated in the field of rhinitis and allergies, and the drugs are mostly antihistamines and hormone drugs. With the deepening of research in the area of ​​intranasal drug delivery, drugs can enter the central nervous system through the nose-brain delivery pathway. The treatment field of nasal spray is expected to expand to vomiting and the central nervous system, treating diseases such as headache (including migraine), epilepsy, Parkinson's disease, Huntington's disease, ALS, Alzheimer's disease, motion sickness, cerebrovascular (including stroke and cerebral infarction), traumatic brain injury, spinal cord injury, anxiety, depression, insomnia, drowsiness, neuroinfection and neuroimmunity (including meningitis, AIDS, cerebral malaria and multiple sclerosis), neurodevelopmental disorders, schizophrenia, cerebral blastoma, opioid addiction, dry eyes and attention deficit hyperactivity disorder (ADHD).

[0003] The key technical difficulty of drugs being able to enter the central nervous system through the nose-brain drug delivery pathway is that the drugs need to be atomized into a soft mist of a certain particle size range in the nasal cavity. The droplet size distribution range of the spray device of various nasal sprays currently on the market is relatively wide, most of the droplet size is greater than 50μm, and the drug liquid spray speed is relatively fast, resulting in a large amount of drug liquid droplets deposited in the nasal vestibule area during drug administration, while the coverage of other functional areas is very low, resulting in a great impact on the bioavailability of the drug, which seriously affects the efficacy of nasal sprays for central nervous system indications. In addition, most of the various nasal sprays on the market are multi-dose systems, and additional antibacterial agents need to be added to the drug liquid to ensure the sterility of the drug during use, and the irritation of the antibacterial agent limits the use of nasal sprays in sensitive patients, elderly patients and infant patients. Therefore, a single-dose sterile nasal spray without preservatives has a significant compliance advantage and a broad market prospect.

[0004] Therefore, a nasal soft mist drug delivery method and device are developed, which can atomize the drug solution into a soft mist with a small particle size (5-500μm), uniform distribution, and slow movement, thereby expanding the nasal drug delivery action area from the nasal vestibule to the olfactory area, middle turbinate, inferior turbinate and nasopharyngeal area, significantly improving the bioavailability of various central nervous system nasal spray drugs, and expanding the indications of nasal drug delivery to diseases such as vomiting, headache (including migraine), epilepsy, Parkinson's disease, Huntington's disease, ALS, Alzheimer's disease, motion sickness, cerebrovascular (including stroke and cerebral infarction), traumatic brain injury, spinal cord injury, anxiety, depression, insomnia, drowsiness, neuroinfection and neuroimmunity (including meningitis, AIDS, cerebral malaria and multiple sclerosis), neurodevelopmental disorders, schizophrenia, cerebral blastoma, opioid addiction, dry eyes and attention deficit hyperactivity disorder (ADHD). In addition, the single-dose nasal spray without preservatives can ensure compliance and portability for sensitive patients, elderly patients and infants. Summary of the invention

[0005] The present invention aims at solving the problems existing in the prior art and provides a nasal soft mist drug delivery method and device.

[0006] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0007] A nasal soft mist drug delivery method comprises the following steps:

[0008] Step 1: Assemble the drug delivery body and the spray adapter;

[0009] Step 2: Place the assembled device flat or inverted and insert the tip of the spray adapter into the nasal cavity;

[0010] Step 3: The squeezed flat or inverted drug delivery body is provided with a cavity filled with air, and the drug is delivered to the nasal cavity through the microporous chip built into the spray adapter to generate soft mist.

[0011] Based on the above technical solution, further, the drug delivery body is a structure containing drugs produced by blow-fill-seal, and the drugs are single-dose sterile solutions or suspensions without preservatives.

[0012] Based on the above technical solution, further, the soft mist particle size range produced is 5-500 μm, preferably 20-150 μm.

[0013] Based on the above technical scheme, further, the drugs include various nasal spray drugs for allergies and rhinitis, various nasal spray drugs for vomiting, various nasal spray drugs for headaches (including migraines), various drugs for epilepsy, various drugs for Parkinson's disease, various drugs for Huntington's disease, various drugs for amyotrophic lateral sclerosis, various drugs for Alzheimer's disease, various drugs for motion sickness, various drugs for cerebrovascular diseases (including stroke and cerebral infarction, etc.), various drugs for traumatic brain injury, various drugs for spinal cord injury, various drugs for anxiety, various drugs for depression, various drugs for insomnia, various drugs for drowsiness, various drugs for neuroinfection and neuroimmunity (including meningitis, AIDS, cerebral malaria and multiple sclerosis, etc.), various drugs for neurodevelopmental disorders, various drugs for schizophrenia, various drugs for cerebral glioma, various drugs for opioid addiction, various drugs for dry eye syndrome, and one or more of various drugs for attention deficit hyperactivity disorder (ADHD).

[0014] Based on the above technical scheme, further, the drugs include various drugs for rhinitis and allergies, such as azelastine, dexamethasone, ipratropium bromide, mometasone, olopatadine, fluticasone, beclomethasone, budesonide, ciclesonide, oxymetazoline, xylometazoline, naphazoline, loratadine, cetirizine, sodium cromoglycate, olopatadine, emmastine, rupatadine, ketotifen, pranlukast, benzimidazol, carbinoxamine, ramatroban, epinastine, bepotastine and pharmaceutically acceptable salts thereof.

[0015] Based on the above technical scheme, further, the drugs include various drugs for vomiting, such as diphenidol, metoclopramide tablets, domperidone, promethazine, buclizine, meclizine, chlorcyclizine, cinnarizine, flunarizine, scopolamine, benzhexol, diphenidol, chlorpromazine, mosapride, ondansetron, alosetron, palonosetron, itasetron, azasetron, ramosetron, indesisetron, dolasetron, granisetron, tropisetron, aprepitant, casopitant, netupitant, fosaprepitant, maropitant, metoclopramide, domperidone, itopride, clebopride, lorazepam, tetrahydrocannabinol, dexamethasone and pharmaceutically acceptable salts thereof, etc.

[0016] Based on the above technical scheme, further, the drugs include various drugs for migraine, such as zolmitriptan, sumatriptan, rizatriptan, eletriptan, lamititan, celecoxib, sodium valproate, ibuprofen, flunarizine, propranolol, almotriptan, lamititan, dihydroergotamine, aspirin, caffeine, acetaminophen, ibuprofen, ubrotriptan, rimegpant, metoclopramide, prochlorperazine, propranolol, metoprolol, verapamil, amitriptyline, sodium valproate, topiramate, CGRP monoclonal antibodies and pharmaceutically acceptable salts thereof, etc.

[0017] Based on the above technical solution, further, the drugs include various drugs for epilepsy, such as diazepam, clonazepam, nitrazepam, chlordiazepoxide, midazolam, lacosamide, cannabidiol, phenobarbital, phenytoin sodium, primidone, amobarbital, fenfluramine, zonisamide, topiramate, isoproterenol, gabapentin, lamotrigine, lelitoline, remacemide, flunarizine, riluzole, sodium valproate and topiramate, oxcarbazepine, denazolidinone, nabendazim, everolimus, Phenytoin sodium, mephenytoin, ethotoin, fosphenytoin sodium, stiripentol, brivaracetam, primidone, carbamate, carbamazepine, ethosuximide, methsuximide, phensuximide, trimethadione, methylethyldione, rufinamide, sodium valproate, phenylacetylurea, phenylbutyrylurea, clobazam, levetiracetam, clonazepam, perampanel, zonisamide, retigabine, acetazolamide, sulthiame, paraformaldehyde, vanillal, chloral hydrate, lidocaine phenytoin sodium and pharmaceutically acceptable salts thereof, etc.

[0018] Based on the above technical scheme, further, the drugs include various drugs for Parkinson's disease, such as levodopa, carbidopa, pramipexole, opioid, tolcapone, trihexyphenidyl, rotigotine, biperiden, piribedil, entacapone, ropinirole, apomorphine, cabergoline, istradefylline, pimavanserin, safinamide, selegiline, rasagiline, zonisamide, droxidopa, vandetanib, adamantane and pharmaceutically acceptable salts thereof.

[0019] Based on the above technical solution, further, the drugs include various drugs for Huntington's disease, trihexyphenidyl, levodopa, selegiline, levodopa, ropinirole, baclofen, aripiprazole, chlorpromazine, haloperidol, risperidone, olanzapine, clozapine and pharmaceutically acceptable salts thereof.

[0020] Based on the above technical solution, further, the drugs include various drugs for ALS, such as riluzole, edaravone, butylphthalide, vitamin E, gabapentin and pharmaceutically acceptable salts thereof.

[0021] Based on the above technical scheme, further, the drugs include various drugs for Alzheimer's disease, such as flubeta-pir, memantine, donepezil, galantamine hydrochloride, galantamine, rivastigmine, rivastigmine, lencanetuzumab, vitamin E, ω-3 fatty acids, curcumin, ginkgo, melatonin and pharmaceutically acceptable salts thereof, etc.

[0022] Based on the above technical solution, further, the drugs include various drugs for motion sickness, such as acetylleucine, diphenhydramine, diprophylline, sodium bicarbonate and pharmaceutically acceptable salts thereof.

[0023] Based on the above technical scheme, further, the drugs include various drugs for stroke, such as edaravone, dextromethorphan, butylphthalide, citicoline, ganglioside, oxiracetam, aniracetam, neuraminic acid, methylcobalamin, cerebroside, neurotropin, cerebroprotein, cinepazide, mouse nerve production factor, aspirin, oryzanol, vitamin B1, vitamin B6, vitamin B12, resveratrol and pharmaceutically acceptable salts thereof.

[0024] Based on the above technical scheme, further, the drugs include various drugs for traumatic brain injury, such as loxoprofen, acetaminophen, ibuprofen, betahistine, flunarizine hydrochloride, piracetam, oxiracetam, mannitol, sulbactam, monosialotetrahexosylganglioside sodium, mannitol, sorbitan, cimetidine and pharmaceutically acceptable salts thereof.

[0025] Based on the above technical solution, further, the drugs include various drugs for spinal cord injury, such as methylprednisolone, methylprednisolone, ganglioside, scopolamine, methylcobalamin, mannitol, dextran, furosemide and pharmaceutically acceptable salts thereof.

[0026] Based on the above technical scheme, further, the drugs include various drugs for anxiety, such as escitalopram, duloxetine, diazepam, lorazepam, oxazepam, clonazepam, sertraline, paroxetine, fluoxetine, venlafaxine, mirtazapine, alprazolam, buspirone, chlordiazepoxide, escitalopram, clomipramine, buspirone and pharmaceutically acceptable salts thereof, etc.

[0027] Based on the above technical scheme, further, the drugs include various drugs for depression, such as ketamine, bupropion, duloxetine, venlafaxine, desvenlafaxine, sertraline, escitalopram, fluvoxamine, dextromethorphan, lumepirone, milnacipran, levmilnacipran, maprotiline, vortioxetine, modafinil, paroxetine salt, trazodone, triptoline, zopiclone, citalopram, selegiline, vilazodone, milnacipran, imipramine, quetiapine, escitalopram, fluoxetine, mirtazapine, vortioxetine, vilazodone, bupropion, nortriptyline, amitriptyline, doxepin, desipramine, tranylcypromine, phenelzine, isocarboxazid, selegiline, aripiprazole, quetiapine, lithium and pharmaceutically acceptable salts thereof, etc.

[0028] Based on the above technical scheme, further, the drugs include various drugs for insomnia, such as diazepam, flurazepam, pineazepam, clorazepam, lormetazepam, midazolam, chloral hydrate, diazepam, estazolam, alprazolam, triazolam, zolpidem tartrate, zaleplon, zopiclone and pharmaceutically acceptable salts thereof.

[0029] Based on the above technical solution, further, the drugs include various drugs for drowsiness, such as methylphenidate, modafinil, amphetamine, pemoline, ritalin, venlafaxine, fluoxetine, sodium oxybate and calcium magnesium potassium and pharmaceutically acceptable salts thereof.

[0030] Based on the above technical solution, further, the drugs include various drugs for neuroinfection and neuroimmunity, such as nerve growth factor, ganglioside, butylphthalide, methylcobalamin, acyclovir, ganciclovir, prednisone, different types of antibiotics and pharmaceutically acceptable salts thereof, etc.

[0031] Based on the above technical solution, further, the drugs include various drugs for neurodevelopmental disorders, such as oxiracetam, piracetam, gangliosides, citicoline, vitamin B1 and pharmaceutically acceptable salts thereof.

[0032] Based on the above technical scheme, further, the drugs include various drugs for schizophrenia, such as chlorpromazine, perphenazine, fluphenazine, thioridazine, haloperidol, penfluridol, chlorprothixene, sulpiride, risperidone, clozapine, olanzapine, quetiapine, asenapine, brepizole, cariprazine, iloperone, lumepirone, lurasidone, paliperidone, aripiprazole, ziprasidone, perospirone, xanomeline, trospium chloride and pharmaceutically acceptable salts thereof.

[0033] Based on the above technical scheme, further, the drugs include various drugs for medulloblastoma, such as PD-1 / PD-L1 monoclonal antibody, bevacizumab, cell immunotherapy drugs, oncolytic virus drugs, bevacizumab, EGFR, dabrafenib / trametinib, temozolomide, beretinib, obitazine, Enzastaurin, Paxalisi, NMS-03305293, ASC40, JL15003, SDT-101 and pharmaceutically acceptable salts thereof, etc.

[0034] Based on the above technical scheme, further, the drugs also include various drugs for opioid addiction, such as naloxone, nalmefene, clonidine, buprenorphine, clonidine, methadone, codeine, oxazepam, alprazolam, temazepam, diazepam, nitrazepam, lobeline, nikethamide, doxapram and pharmaceutically acceptable salts thereof.

[0035] Based on the above technical solution, further, the drugs include various drugs for dry eye, such as varenicline and its pharmaceutically acceptable salts.

[0036] Based on the above technical scheme, further, the drugs include various drugs for attention deficit hyperactivity disorder (ADHD), such as dextroamphetamine, bupropion, desipramine, imipramine, nortriptyline, viloxazine, lisdexamfetamine, methylphenidate, dexmethylphenidate, atomoxetine, guanfacine, clonidine, lisdexamfetamine and pharmaceutically acceptable salts thereof.

[0037] A nasal soft mist drug delivery device comprises a drug delivery body and a spray adapter; the spray adapter is connected to the drug delivery body, and a first cavity and a second cavity which are connected are arranged in the drug delivery body; a microporous chip is loaded on the spray adapter, and the drug in the cavity is delivered through the microporous chip.

[0038] Based on the above technical solution, further, it also includes a connecting piece for connecting the dosing body and the spray adapter, the spray adapter is also provided with a guide part, the connecting piece is provided with a through hole, the guide part is provided in the through hole, and one end of the guide part is a pointed structure, the inner wall of the through hole is provided with a first limiting part and a second limiting part, and a first groove structure is provided between the first limiting part and the second limiting part, the end of the dosing body is provided with a first convex part, the first convex part cooperates with the first groove, the outer surface of the dosing body is provided with a second convex part, the connecting piece is provided with a second groove, and one end of the second convex part extends to be limited in the second groove.

[0039] Based on the above technical solution, further, the end of the drug delivery body is provided with an external thread structure, the spray adapter is provided with an internal thread structure, and the drug delivery body and the spray adapter are directly connected through the thread structure.

[0040] Based on the above technical solution, further, the microporous chip is provided with a plurality of nozzles, and the diameter of the nozzles ranges from 1 μm to 100 μm.

[0041] Based on the above technical solution, further, the size, dimension and material of the drug delivery body are adjusted according to actual needs, and the material selection of the drug delivery body includes but is not limited to polyethylene, LDPE, LLDPE, HDPE, and polypropylene.

[0042] A nasal soft mist drug delivery device is used for rhinitis, allergy, vomiting and central nervous system related indications.

[0043] Based on the above technical solution, further, central nervous system related indications include but are not limited to headache (including migraine), epilepsy, Parkinson's disease, Huntington's disease, ALS, Alzheimer's disease, motion sickness, cerebrovascular disease (including stroke and cerebral infarction, etc.), traumatic brain injury, spinal cord injury, anxiety, depression, insomnia, drowsiness, neuroinfection and neuroimmunity (including meningitis, AIDS, cerebral malaria and multiple sclerosis, etc.), neurodevelopmental disorders, schizophrenia, cerebral blastoma, opioid addiction, dry eyes, attention deficit hyperactivity disorder (ADHD) and other diseases.

[0044] Compared with the prior art, the present invention has the following beneficial effects:

[0045] The present invention provides a nasal soft mist drug delivery device, method and application, which is portable and can efficiently and quickly atomize a single-dose sterile solution or suspension without preservatives into a slow-moving soft mist. The droplet size after atomization is small and evenly distributed (5-500 μm), which can be more diffused and deposited in all nasal areas, significantly improving the total coverage of each nasal area of ​​the patient, thereby greatly improving the bioavailability of the drug. Secondly, compared with most multi-dose nasal sprays on the market, the nasal soft mist delivery has significant advantages, providing an effective solution for sensitive patients, elderly patients, infants and young children. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 This is a front view of the nasal soft mist drug delivery device of the present invention;

[0047] Figure 2 for Figure 1 Side view of

[0048] Figure 3 for Figure 2 A partial structural diagram of

[0049] Figure 4 A schematic diagram of the structure of assembling multiple drug delivery devices of the present invention;

[0050] Figure 5It is a front view of the drug delivery device of the present invention without a connecting piece;

[0051] Figure 6 It is a side view of the drug delivery device of the present invention without a connecting piece;

[0052] Figure 7 It is a schematic structural diagram of a plurality of drug delivery devices without connectors provided in the present invention;

[0053] Figure 8 is the particle size distribution diagram of sample 1 of the present invention;

[0054] Fig. 9 This is the particle size distribution diagram of sample 2 of the present invention;

[0055] Figure numerals: 1. dosing body; 2. spray adapter; 3. microporous chip; 4. connector; 5. labeling part; 6. guide part; 7. first limiting part; 8. second limiting part; 9. first groove; 10. first convex part; 11. second convex part; 12. second groove; 13. tip structure; 14. first cavity; 15. second cavity; 16. end cover; 17. recess. DETAILED DESCRIPTION

[0056] The present invention is further elaborated and described below in conjunction with the accompanying drawings and specific embodiments. The technical features of each embodiment of the present invention can be combined accordingly without conflicting with each other. In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific embodiments of the present invention are described in detail below in conjunction with the accompanying drawings. In the following description, many specific details are described to facilitate a full understanding of the present invention. However, the present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present invention, so the present invention is not limited by the specific embodiments disclosed below. The technical features in each embodiment of the present invention can be combined accordingly without conflicting with each other.

[0057] In the description of the present invention, it is to be understood that when an element is considered to be "connected" to another element, it may be directly connected to the other element or indirectly connected, i.e., there is an intermediate element. On the contrary, when an element is said to be "directly" connected to another element, there is no intermediate element. In the description of the present invention, it is to be understood that the terms "first" and "second" are only used to distinguish the purpose of description, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features. Thus, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features.

[0058] Example 1

[0059] like Figure 1-Figure 7As shown, a nasal soft mist drug delivery device comprises a drug delivery body 1 and a spray adapter 2; the spray adapter 2 is connected to the end of the drug delivery body 1; a recess 17 is provided on the drug delivery body 1, and the recess 17 divides the internal cavity of the drug delivery body 1 into a first accommodating cavity 14 and a second accommodating cavity 15 that are connected; a microporous chip 3 is loaded on the spray adapter 2, and the microporous chip 3 is arranged opposite to the end of the drug delivery body 1. Among them, one embodiment is as follows, Figure 1 As shown, the spray adapter 2 is connected to the end of the drug delivery body 1 through a connector 4; another embodiment is as follows Figure 5 As shown, the spray adapter 2 is directly threadedly connected to the end of the dosing body 1 through a threaded structure.

[0060] Specifically, the microporous chip 3 is provided with a plurality of spray holes, and the diameter of the spray holes ranges from 1 μm to 100 μm, preferably from 1 μm to 30 μm. It should be explained that the microporous chip 3 refers to a structure in which a spray hole of a specified size is opened on a chip material such as silicon-based, carbon-based, copper, stainless steel, etc. By setting the aperture of the spray holes of different sizes, the liquid medicine in the internal cavity can be sprayed into a soft mist in the shape of droplets of different sizes, which is a conventional phenomenon in this field. The connector 4 is provided with an external thread structure, and the inside of the spray adapter 2 is an internal thread structure, and the connector 4 and the spray adapter 2 are threadedly connected. The spray adapter 2 is also provided with a guide portion 6, and the connector 4 is provided with a through hole. The guide portion 6 is provided in the through hole, and one end of the guide portion 6 is a tip structure 13, and the tip structure 13 is provided with a liquid outlet. The tip structure 13 is provided to facilitate the spray adapter 2 to communicate with the drug delivery body 1. When in use, the tip structure 13 is inserted into the end of the drug delivery body 1, and the structure is tilted so that the top of the spray adapter 2 is inserted into the nasal cavity. The drug in the drug delivery body 1 flows into the first accommodating cavity 14, and enters the spray adapter 2 through the liquid outlet of the tip structure 13. By squeezing the second accommodating cavity 15, pressure is formed, and the solution entering the spray adapter 2 is sprayed out through the spray hole on the microporous chip 3 under the action of pressure. The inner wall of the through hole is provided with a first limiting portion 7 and a second limiting portion 8, and a first groove 9 structure is provided between the first limiting portion 7 and the second limiting portion 8. A side wall of the second limiting portion 8 and the inner wall of the connector 4 are provided with an inclined angle. The inclined structure is provided to facilitate the installation of the end of the drug delivery body 1 and the connector 4, and to avoid unnecessary damage to the end of the drug delivery body 1 and the inside of the connector 4 due to excessive friction. The end of the drug delivery body 1 is provided with a first convex portion 10, and the first convex portion 10 cooperates with the first groove 9. The lower end of the drug delivery body 1 is provided with a labeling portion 5, and an information label is attached to the labeling portion 5. The outer surface of the drug delivery body 1 is provided with a second convex portion 11, and the connecting member 4 is provided with a second groove 12, and one end of the second convex portion 11 extends and is limited to the second groove 12.

[0061] Among them, the size and material of the drug delivery body 1 can be adjusted according to actual needs. For example, the material of the drug delivery body 1 can be selected from polyethylene, LDPE, LLDPE, HDPE, polypropylene, etc. The liquid medicine in the drug delivery body 1 is a sterile liquid preparation without adding antibacterial agents. The bottle type, size and internal volume of the vial made of LDPE and other materials can be adjusted to meet the filling requirements of different drugs.

[0062] The drug administration operation principle of the present device is: before use, unscrew the end cap 16 for sealing at the upper end of the drug administration body 1, and directly thread the spray adapter 2 to the end of the drug administration body 1. It should be noted that, whether it is a soft material or a hard material, the spray adapter 2 and the end of the drug administration body 1 can achieve a threaded connection effect, or, the spray adapter 2 is connected to the end of the drug administration body 1 through the bayonet structure of the connector 4. When the connector 4 is used for connection, the connector 4 is installed on the upper end of the drug administration body 1, and the first limiting portion 7, the second limiting portion 8 and the first groove 9 of the connector 4 are engaged with the first convex portion 10 of the drug administration body 1, and the second groove 12 of the connector 4 is engaged with the second convex portion 11 of the drug administration body 1; the spray adapter 2 is inserted into the passage in the connector 4, and the spray adapter 2 pierces the top of the drug administration body 1 through the tip structure 13 and is inserted into the drug administration body 1. Specifically, when in use, the drug delivery body 1 is inverted or placed horizontally so that the drug in the second cavity 15 of the drug delivery body 1 enters the first cavity 14, and the upper end of the spray adapter 2 is inserted into the nasal cavity, the head is tilted, and the drug delivery device is tilted so that the drug is concentrated in the first cavity 14 of the drug delivery body, and the second cavity 15 of the drug delivery body 1 is squeezed manually. The drug enters the spray adapter 2 through the pores on the tip structure 13 of the spray adapter 2, and the drug is atomized through the microporous chip 3 to produce soft mist, which enters the nasal cavity to achieve drug delivery. It should be explained that the pressure of artificial squeezing is greater than 80Kpa. It has been verified that the squeezing pressure is sufficient to spray the drug through the spray hole and produce droplets or soft mist. Further, the meaning of soft mist in this embodiment is: the output mist with small droplet size, slow spray speed, and long single spray duration is called "soft mist". During the squeezing process, the device combines the aperture size of the spray hole and the collision of structures such as the spray adapter 2 to generate soft mist. The target particle size of the output soft mist is 5-500μm, and the optimal range is 20-150μm.

[0063] Example 2

[0064] A nasal soft mist drug delivery method comprises the following steps: step 1: assembling a drug delivery body and a spray adapter; step 2: placing the assembled device flat or inverted, and inserting the top of the spray adapter into the nasal cavity; step 3: squeezing the flat or inverted drug delivery body provided with a cavity filled with air, and the drug generates soft mist through a microporous chip built into the spray adapter, and enters the nasal cavity for delivery. The particle size of the soft mist generated is in the range of 5-500 μm, preferably 20-150 μm.

[0065] The drugs include various nasal spray drugs for allergies and rhinitis, various nasal spray drugs for vomiting, various nasal spray drugs for headaches (including migraines), various drugs for epilepsy, various drugs for Parkinson's disease, various drugs for Huntington's disease, various drugs for amyotrophic lateral sclerosis, various drugs for Alzheimer's disease, various drugs for motion sickness, various drugs for cerebrovascular diseases (including stroke and cerebral infarction, etc.), various drugs for traumatic brain injury, various drugs for spinal cord injury, various drugs for anxiety, various drugs for depression, various drugs for insomnia, various drugs for drowsiness, various drugs for neuroinfection and neuroimmunity (including meningitis, AIDS, cerebral malaria and multiple sclerosis, etc.), various drugs for neurodevelopmental disorders, various drugs for schizophrenia, various drugs for brain glioma, various drugs for opioid addiction, various drugs for dry eye syndrome, and one or more of various drugs for attention deficit hyperactivity disorder (ADHD).

[0066] Furthermore, the drugs include various drugs for rhinitis and allergies, such as azelastine, dexamethasone, ipratropium bromide, mometasone, olopatadine, fluticasone, beclomethasone, budesonide, ciclesonide, oxymetazoline, xylometazoline, naphazoline, loratadine, cetirizine, sodium cromoglycate, olopatadine, emmastine, rupatadine, ketotifen, pranlukast, benzimidazol, carbinoxamine, ramatroban, epinastine, bepotastine and pharmaceutically acceptable salts thereof.

[0067] Furthermore, the drugs include various drugs for vomiting, such as diphenidol, metoclopramide tablets, domperidone, promethazine, buclizine, meclizine, chlorcyclizine, cinnarizine, flunarizine, scopolamine, benzhexol, diphenidol, chlorpromazine, mosapride, ondansetron, alosetron, palonosetron, itasetron, azasetron, ramosetron, indesisetron, dolasetron, granisetron, tropisetron, aprepitant, casopitant, netupitant, fosaprepitant, maropitant, metoclopramide, domperidone, itopride, clebopride, lorazepam, tetrahydrocannabinol, dexamethasone and pharmaceutically acceptable salts thereof, etc.

[0068] Furthermore, the drugs include various drugs for migraine, such as zolmitriptan, sumatriptan, rizatriptan, eletriptan, lamititan, celecoxib, sodium valproate, ibuprofen, flunarizine, propranolol, almotriptan, lamititan, dihydroergotamine, aspirin, caffeine, acetaminophen, ibuprofen, ubrotriptan, rimegpant, metoclopramide, prochlorperazine, propranolol, metoprolol, verapamil, amitriptyline, sodium valproate, topiramate, CGRP monoclonal antibodies and pharmaceutically acceptable salts thereof, etc.

[0069] Furthermore, the drugs include various drugs for epilepsy, such as diazepam, clonazepam, nitrazepam, chlordiazepoxide, midazolam, lacosamide, cannabidiol, phenobarbital, phenytoin, primidone, amobarbital, fenfluramine, zonisamide, topiramate, isoproterenol, gabapentin, lamotrigine, lelitoline, remacemide, flunarizine, riluzole, sodium valproate and topiramate, oxcarbazepine, denazolidinone, nabendazim, everolimus, phenytoin sodium , mephenytoin, ethotoin, fosphenytoin sodium, stiripentol, brivaracetam, primidone, carbamate, carbamazepine, ethosuximide, methsuximide, phensuximide, trimethadione, methylethyldione, rufinamide, sodium valproate, phenylacetyl urea, phenylbutyryl urea, clobazam, levetiracetam, clonazepam, perampanel, zonisamide, retigabine, acetazolamide, sulthiame, paraformaldehyde, vanillal, chloral hydrate, lidocaine phenytoin sodium and pharmaceutically acceptable salts thereof, etc.

[0070] Furthermore, the drugs include various drugs for Parkinson's disease, such as levodopa, carbidopa, pramipexole, opioid, tolcapone, trihexyphenidyl, rotigotine, biperiden, piribedil, entacapone, ropinirole, apomorphine, cabergoline, istraphylline, pimavanserin, safinamide, selegiline, rasagiline, zonisamide, droxidopa, vandetanib, adamantane and pharmaceutically acceptable salts thereof.

[0071] Furthermore, the drugs include various drugs for Huntington's disease, trihexyphenidyl, levodopa, selegiline, levodopa, ropinirole, baclofen, aripiprazole, chlorpromazine, haloperidol, risperidone, olanzapine, clozapine and pharmaceutically acceptable salts thereof.

[0072] Furthermore, the drugs include various drugs for ALS, such as riluzole, edaravone, butylphthalide, vitamin E, gabapentin and pharmaceutically acceptable salts thereof.

[0073] Furthermore, the drugs include various drugs for Alzheimer's disease, such as flubeta-pir, memantine, donepezil, galantamine hydrochloride, galantamine, rivastigmine, rivastigmine, lencanetumab, vitamin E, ω-3 fatty acids, curcumin, ginkgo, melatonin and pharmaceutically acceptable salts thereof, etc.

[0074] Furthermore, the drugs include various drugs for motion sickness, such as acetylleucine, diphenhydramine, diprophylline, sodium bicarbonate and pharmaceutically acceptable salts thereof.

[0075] Furthermore, the drugs include various drugs for stroke, such as edaravone, dextromethorphan, butylphthalide, citicoline, ganglioside, oxiracetam, aniracetam, neuraminic acid, methylcobalamin, cerebroside, neurotropin, cerebroprotein, cinepazide, mouse nerve growth factor, aspirin, oryzanol, vitamin B1, vitamin B6, vitamin B12, resveratrol and pharmaceutically acceptable salts thereof.

[0076] Furthermore, the drugs include various drugs for traumatic brain injury, such as loxoprofen, acetaminophen, ibuprofen, betahistine, flunarizine hydrochloride, piracetam, oxiracetam, mannitol, sulbactam, monosialotetrahexosylganglioside sodium, mannitol, sorbitan, cimetidine and pharmaceutically acceptable salts thereof.

[0077] Furthermore, the drugs include various drugs for spinal cord injury, such as methylprednisolone, methylprednisolone, ganglioside, scopolamine, methylcobalamin, mannitol, dextran, furosemide and pharmaceutically acceptable salts thereof.

[0078] Furthermore, the drugs include various types of drugs for anxiety, such as escitalopram, duloxetine, diazepam, lorazepam, oxazepam, clonazepam, sertraline, paroxetine, fluoxetine, venlafaxine, mirtazapine, alprazolam, buspirone, chlordiazepoxide, escitalopram, clomipramine, buspirone and pharmaceutically acceptable salts thereof, etc.

[0079] Furthermore, the drugs include various drugs for depression, such as ketamine, bupropion, duloxetine, venlafaxine, desvenlafaxine, sertraline, escitalopram, fluvoxamine, dextromethorphan, lumepirone, milnacipran, levmilnacipran, maprotiline, vortioxetine, modafinil, paroxetine salt, trazodone, triptoline, zopiclone, citalopram, selegiline, vilazodone, milnacipran, imipramine, quetiapine, escitalopram, fluoxetine, mirtazapine, vortioxetine, vilazodone, bupropion, nortriptyline, amitriptyline, doxepin, desipramine, tranylcypromine, phenelzine, isocarboxazid, selegiline, aripiprazole, quetiapine, lithium and pharmaceutically acceptable salts thereof, etc.

[0080] Furthermore, the drugs include various drugs for insomnia, such as diazepam, flurazepam, pineazepam, clorazepam, lormetazepam, midazolam, chloral hydrate, diazepam, estazolam, alprazolam, triazolam, zolpidem tartrate, zaleplon, zopiclone and pharmaceutically acceptable salts thereof.

[0081] Furthermore, the drugs include various drugs for drowsiness, such as methylphenidate, modafinil, amphetamine, pemoline, ritalin, venlafaxine, fluoxetine, sodium oxybate and calcium magnesium potassium and pharmaceutically acceptable salts thereof.

[0082] Furthermore, the drugs include various drugs for neuroinfection and neuroimmunity, such as nerve growth factor, ganglioside, butylphthalide, methylcobalamin, acyclovir, ganciclovir, prednisone, different types of antibiotics and pharmaceutically acceptable salts thereof, etc.

[0083] Furthermore, the drugs include various drugs for neurodevelopmental disorders, such as oxiracetam, piracetam, gangliosides, citicoline, vitamin B1 and pharmaceutically acceptable salts thereof.

[0084] Furthermore, the drugs include various drugs for schizophrenia, such as chlorpromazine, perphenazine, fluphenazine, thioridazine, haloperidol, penfluridol, chlorprothixene, sulpiride, risperidone, clozapine, olanzapine, quetiapine, asenapine, brepirazole, cariprazine, iloperone, lumepirone, lurasidone, paliperidone, aripiprazole, ziprasidone, perospirone, xanomeline, trospium chloride and pharmaceutically acceptable salts thereof.

[0085] Furthermore, the drugs include various drugs for medulloblastoma, such as PD-1 / PD-L1 monoclonal antibodies, bevacizumab, cell immunotherapy drugs, oncolytic virus drugs, bevacizumab, EGFR, dabrafenib / trametinib, temozolomide, berritinib, obitatinib, enzastaurin, Paxalisi, NMS-03305293, ASC40, JL15003, SDT-101 and pharmaceutically acceptable salts thereof, etc.

[0086] Furthermore, the drugs also include various drugs for opioid addiction, such as naloxone, nalmefene, clonidine, buprenorphine, clonidine, methadone, codeine, oxazepam, alprazolam, temazepam, diazepam, nitrazepam, lobeline, nikethamide, doxapram and pharmaceutically acceptable salts thereof.

[0087] Furthermore, the drugs include various drugs for dry eye, such as varenicline and pharmaceutically acceptable salts thereof.

[0088] Furthermore, the drugs include various drugs for attention deficit hyperactivity disorder (ADHD), such as dextroamphetamine, bupropion, desipramine, imipramine, nortriptyline, viloxazine, lisdexamfetamine, methylphenidate, dexmethylphenidate, atomoxetine, guanfacine, clonidine, lisdexamfetamine and pharmaceutically acceptable salts thereof.

[0089] The droplet size distribution of sumatriptan after atomization was compared by combining the present device and method with the existing commercially available device, as follows:

[0090] 1. Prepare sumatriptan nasal spray solution, see Table 1, fill it into a small bottle made of LDPE or other materials produced by blow-fill-seal, that is, in the drug delivery body, and connect the nasal spray adapter to the small bottle made of LDPE or other materials, as sample 1. Take another sumatriptan nasal spray solution and fill it into a commercially available nasal spray device, as sample 2. The droplet particle size distribution of the two groups of samples is measured by the Synpatek laser particle size tester, and the results are compared. The results are shown in Table 2.

[0091] Table 1 Sumatriptan nasal spray solution

[0092] Element Dosage(g) Sumatriptan 0.25 Potassium dihydrogen phosphate 0.08 Disodium hydrogen phosphate 0.007 sulfuric acid 0.05 Sodium hydroxide Adjust pH to 6.0 Water for injection Make up to 5ml

[0093] Table 2

[0094] Device D10 D50 D90 Nasal soft mist drug delivery device 8.06μm 16.05μm 24.67μm Commercially available nasal spray devices 0.40μm 35.84μm 78.02μm

[0095] According to the results in the table above, compared with the atomization effect of the spray device of the commercially available nasal spray under the same conditions, combined with the data of D10-D90, for example, the D90 of the nasal soft mist drug delivery device is 24.67μm, and the D50 is 16.05μm, while the D90 of the commercially available device is 78.02μm, and the D50 is 35.84μm. The droplet size distribution range of the atomized nasal soft mist drug delivery device in this scheme is narrow, and the uniformity has a significant advantage. And the droplet size range sprayed by this device meets the set range.

[0096] Example 3

[0097] Based on the administration method described in Example 1 and Example 2, the droplet particle size distribution of azelastine hydrochloride and fluticasone propionate drugs was compared in combination with the nasal soft mist administration device and the commercially available nasal inhalation device. The specific analysis is as follows: prepare azelastine hydrochloride and fluticasone propionate nasal sprays, see Table 3, fill them into vials made of LDPE or other materials of the nasal soft mist administration device, and connect the nasal spray adapter to the vial made of LDPE or other materials, as Sample 3. Take azelastine hydrochloride and fluticasone propionate nasal sprays and fill them into a commercially available nasal spray device, as Sample 4. The droplet particle size distribution of the two groups of samples is measured by the Synpatek laser particle size tester and compared. The results are shown in Table 4.

[0098] Table 3 Azelastine hydrochloride nasal spray solution

[0099] Element Dosage(g) Azelastine Hydrochloride 0.15 Fluticasone Propionate 0.05475 Microcrystalline cellulose and sodium carboxymethyl cellulose 4.5 Glycerol 5 Phenylethyl alcohol 0.5 Sodium EDTA 0.02 Twain 80 0.01 Water for injection Make up to 150ml

[0100] Table 4

[0101] Device D10 D50 D90 Nasal soft mist drug delivery device 7.39μm 16.04μm 26.06μm Commercially available nasal spray devices 0.55μm 36.07μm 77.95μm

[0102] According to the results in the table above, compared with the atomization effect of the spray device of the commercially available nasal spray under the same conditions, combined with the data of D10-D90, for example, the D90 of the nasal soft mist drug delivery device is 26.06μm, and the D50 is 16.04μm, while the D90 of the commercially available device is 77.95μm, and the D50 is 36.07μm. The droplet size distribution of the nasal soft mist drug delivery device in this scheme is relatively narrow, and the uniformity has a significant advantage. And the droplet size range sprayed by this device meets the set range.

[0103] Example 4

[0104] Based on Example 1 and Example 2, the droplet particle size distribution of the budesonide drug was compared in combination with the nasal soft mist drug delivery device and the commercially available device. The specific analysis is as follows: prepare budesonide nasal spray, see Table 5, fill it into a vial of LDPE or other materials of the nasal soft mist drug delivery device, and connect the nasal spray adapter to the vial of LDPE or other materials as sample 5. Take another budesonide nasal spray and fill it in a commercially available nasal spray device as sample 6. The droplet particle size distribution of the two groups of samples is measured by the Synpatek laser particle size tester, and compared. The results are shown in Table 6.

[0105] Table 5 Budesonide nasal spray solution

[0106] Element Dosage(g) Budesonide 2.56 Microcrystalline cellulose and sodium carboxymethyl cellulose 45 glucose 200 Sodium EDTA 0.5 Twain 80 0.7 hydrochloric acid Adjust pH to 5.0 Water for injection Make up to 4000ml

[0107] Table 6

[0108] Device D10 D50 D90 Nasal soft mist drug delivery device 7.96μm 16.88μm 27.00μm Commercially available nasal spray devices 0.51μm 36.06μm 76.89μm

[0109] According to the results in the table above, compared with the atomization effect of the spray device of the commercially available nasal spray under the same conditions, combined with the data of D10-D90, for example, the D90 of the nasal soft mist drug delivery device is 27.00μm, and the D50 is 16.88μm, while the D90 of the commercially available device is 76.89μm, and the D50 is 36.06μm. The droplet size distribution of the nasal soft mist drug delivery device in this scheme is relatively narrow, and the uniformity has a significant advantage. And the droplet size range sprayed by this device meets the set range.

[0110] Example 5

[0111] Based on Example 1 and Example 2, the droplet particle size distribution of the fluticasone propionate drug was compared in combination with the nasal soft mist drug delivery device and the commercially available device, and the specific analysis was as follows: a fluticasone propionate nasal spray was prepared, see Table 7, filled into a vial of LDPE or other materials of the nasal soft mist drug delivery device, and the nasal spray adapter was connected to the vial of LDPE or other materials, as Sample 7. Another fluticasone propionate nasal spray was filled into a commercially available nasal spray device, as Sample 8. The droplet particle size distribution of the two groups of samples was measured by a Synpatek laser particle size tester, and compared. The results are shown in Table 8.

[0112] Table 7 Fluticasone propionate nasal spray solution

[0113] Element Dosage(g) Fluticasone Propionate 2.56 glucose 300 Microcrystalline cellulose and sodium carboxymethyl cellulose 70 Phenylethyl alcohol 15 Twain 80 0.5 Water for injection Make up to 5000ml

[0114] Table 8

[0115] Device D10 D50 D90 Nasal soft mist drug delivery device 8.06μm 16.05μm 24.67μm Commercially available nasal spray devices 0.59μm 37.21μm 80.14μm

[0116] According to the results in the table above, compared with the atomization effect of the spray device of the commercially available nasal spray under the same conditions, combined with the data of D10-D90, for example, the D90 of the nasal soft mist drug delivery device is 24.67μm, and the D50 is 16.05μm, while the D90 of the commercially available device is 80.14μm, and the D50 is 37.21μm. The droplet size distribution of the nasal soft mist drug delivery device in this scheme is relatively narrow, and the uniformity has a significant advantage. And the droplet size range sprayed by this device meets the set range.

[0117] Example 6

[0118] Based on Example 1 and Example 2, the droplet particle size distribution of granisetron hydrochloride after atomization was compared in combination with the nasal soft mist drug delivery device and the commercially available device. The specific analysis is as follows: prepare a granisetron hydrochloride nasal spray, see Table 9, fill it into a vial of LDPE or other materials of the nasal soft mist drug delivery device, and connect the nasal spray adapter to the vial of LDPE or other materials as sample 9. Take another granisetron hydrochloride spray and fill it in a commercially available nasal spray device as sample 10. The droplet particle size distribution of the two groups of samples is measured by the Synpatek laser particle size tester and compared. The results are shown in Table 10.

[0119] Table 9 Granisetron hydrochloride nasal spray solution

[0120] Element Dosage(g) Granisetron Hydrochloride 11.0 Sodium chloride 45 Water for injection Make up to 5000ml

[0121] Table 10

[0122] Device D10 D50 D90 Nasal soft mist drug delivery device 8.55μm 17.24μm 23.15μm Commercially available nasal spray devices 2.05μm 36.28μm 72.39μm

[0123] According to the results in the table above, compared with the droplets produced by the spray device of the commercially available nasal spray under the same conditions, combined with the data of D10-D90, for example, the D90 of the nasal soft mist drug delivery device is 23.15μm, and the D50 is 17.24μm, while the D90 of the commercially available device is 72.39μm, and the D50 is 36.28μm. The droplet size distribution of the nasal soft mist drug delivery device in this scheme is relatively narrow, and the uniformity has a significant advantage. And the droplet size range of the sprayed droplets of this device meets the set range.

[0124] Example 7

[0125] Based on Example 1 and Example 2, the distribution of the nasal area after administration with the nasal soft mist drug delivery device is characterized as follows:

[0126] A certain amount of calcein powder was weighed and dissolved in 1 mol / L sodium hydroxide solution, and mixed with 25% glycerol solution to prepare a fluorescent indicator solution with a certain viscosity. The solution was filled into a nasal soft mist drug delivery device, and the device was used to simulate nasal spray delivery to a silicone nasal model (sample 11). Ultraviolet lamp was used as the light source, and fluorescent imaging was collected by a digital camera in a dark room, thereby intuitively displaying the distribution of the drug in the nasal area.

[0127] From the actual imaging results, it can be seen that the soft mist atomized by the single-dose nasal soft mist drug delivery device of this scheme has a high area coverage rate in the nasal area. Except for the nasopharyngeal area, the olfactory area, middle turbinate area, inferior turbinate area and nasal vestibule are all well distributed, indicating that the drug can exert its effect in various areas.

[0128] Example 8

[0129] Based on Example 1 and Example 2, the distribution of the nasal soft mist drug delivery device and the commercially available nasal spray device after spray delivery is compared as follows:

[0130] The fluorescent indicator solution prepared in Example 7 was respectively filled into the nasal soft mist drug delivery device of the present invention (Sample 12) and the commercially available nasal spray device (Sample 13), and the nasal spray drug delivery was performed on the silicone nasal model. An ultraviolet lamp was used as the ultraviolet light source. Fluorescent imaging photos of different groups were collected by a digital camera in a dark room, and the pictures were analyzed by software to calculate the coverage of each area, thereby comparing the intranasal area distribution of nasal spray drug delivery by different devices. The results are shown in Table 11.

[0131] Table 11

[0132]

[0133] From the comparison results of the silicone nasal model imaging, it can be seen that compared with the commercially available nasal spray devices, the nasal spray soft mist drug delivery device of this scheme can not only achieve the commercially available coverage rate in the nasal vestibule, but also has significant advantages in the total coverage rate and the single coverage rate of other areas (except the nasopharyngeal area), indicating that the nasal soft mist drug delivery device of this scheme can greatly improve the bioavailability of various nasal sprays, especially central nervous system nasal sprays.

[0134] In summary, this solution provides a better solution for various nasal sprays on the market, especially central nervous system nasal sprays. The single-dose nasal soft mist drug delivery device of this solution can atomize the drug solution into a soft mist with a small particle size (5-500μm), uniform distribution, and slow movement. The preferred particle size range is 20-150μm, which significantly improves the bioavailability of this type of drug. Secondly, compared with most multi-dose nasal sprays on the market, the nasal soft mist delivery has significant advantages, providing an effective solution for sensitive patients, elderly patients, infants and young children.

[0135] Example 9

[0136] Based on Example 1 and Example 2, an application of a nasal soft mist drug delivery device is applied to rhinitis, anti-allergy and central nervous system related indications. Specifically, central nervous system related indications include but are not limited to headache (including migraine), epilepsy, Parkinson's disease, Huntington's disease, ALS, Alzheimer's disease, motion sickness, cerebrovascular (including stroke and cerebral infarction, etc.), traumatic brain injury, spinal cord injury, anxiety, depression, insomnia, drowsiness, neuroinfection and neuroimmunity (including meningitis, AIDS, cerebral malaria and multiple sclerosis, etc.), neurodevelopmental disorders, schizophrenia, cerebral blastoma, opioid addiction, dry eyes, attention deficit hyperactivity disorder (ADHD) and other diseases.

[0137] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A nasal soft mist drug delivery method, characterized in that: The following steps are involved: Step 1: Assemble the drug delivery body and the spray adapter; Step 2: Place the assembled device flat or inverted and insert the tip of the spray adapter into the nasal cavity; Step 3: The squeezed flat or inverted drug delivery body is provided with a cavity filled with air, and the drug is delivered to the nasal cavity through the microporous chip built into the spray adapter to generate soft mist.

2. A nasal soft mist drug delivery method according to claim 1, wherein the drug delivery body is a structure containing a drug produced by blow-fill-seal, and the drug is a single-dose sterile solution or suspension without a preservative.

3. A nasal soft mist drug delivery method according to claim 1, wherein the particle size of the soft mist produced is in the range of 5-500 μm, preferably 20-150 μm.

4. A nasal soft mist drug delivery method according to claim 1, wherein the drugs include various drugs for rhinitis and allergies, various drugs for vomiting, various drugs for headaches, various drugs for epilepsy, various drugs for Parkinson's disease, various drugs for Huntington's disease, various drugs for amyotrophic lateral sclerosis, various drugs for Alzheimer's disease, various drugs for motion sickness, various drugs for cerebrovascular diseases, various drugs for traumatic brain injury, various drugs for spinal cord injury, various drugs for anxiety, various drugs for depression, various drugs for insomnia, various drugs for drowsiness, various drugs for neuroinfection and neuroimmunity, various drugs for neurodevelopmental disorders, various drugs for schizophrenia, various drugs for brain glioma, various drugs for opioid addiction, various drugs for dry eye syndrome, and various drugs for attention deficit hyperactivity disorder.

5. A nasal soft mist drug delivery device, using a nasal soft mist drug delivery method according to any one of claims 1 to 4, characterized in that: It comprises a drug delivery body and a spray adapter; the spray adapter is connected to the drug delivery body, and a first cavity and a second cavity which are connected are arranged in the drug delivery body; a microporous chip is loaded on the spray adapter, and the medicine in the cavity is delivered through the microporous chip.

6. A nasal soft mist drug delivery device according to claim 5, characterized in that: It also includes a connector for connecting a dosing body and a spray adapter. The spray adapter is also provided with a guide portion. The connector is provided with a through hole. The guide portion is provided in the through hole, and one end of the guide portion is a pointed structure. The inner wall of the through hole is provided with a first limiting portion and a second limiting portion, and a first groove structure is provided between the first limiting portion and the second limiting portion. A first convex portion is provided at the end of the dosing body, and the first convex portion cooperates with the first groove. A second convex portion is provided on the outer surface of the dosing body, and a second groove is provided on the connector. One end of the second convex portion extends and is limited to the second groove.

7. A nasal soft mist drug delivery device according to claim 5, characterized in that: The end of the drug delivery body is provided with an external thread structure, the spray adapter is provided with an internal thread structure, and the drug delivery body and the spray adapter are directly connected through the thread structure.

8. The nasal soft mist drug delivery device according to claim 5, characterized in that: The microporous chip is provided with a plurality of spray holes, and the diameter of the spray holes ranges from 1 μm to 100 μm.

9. A nasal soft mist drug delivery device according to claim 5, characterized in that: The size, dimension and material of the drug delivery body are adjusted according to actual needs, and the material selection of the drug delivery body includes but is not limited to polyethylene, LDPE, LLDPE, HDPE, and polypropylene.

10. An application of a nasal soft mist drug delivery device, characterized in that: It is used for rhinitis, allergies, vomiting and central nervous system related indications. Central nervous system related indications include but are not limited to headache, epilepsy, Parkinson's disease, Huntington's disease, ALS, Alzheimer's disease, motion sickness, cerebrovascular disease, traumatic brain injury, spinal cord injury, anxiety, depression, insomnia, drowsiness, neuroinfection and neuroimmunity, neurodevelopmental disorders, schizophrenia, glioma, opioid addiction, dry eyes and attention deficit hyperactivity disorder.

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