Nasal delivery device

• US 10,549,052 B2
• Filed: 02/28/2013
• Issued: 02/04/2020
• Est. Priority Date: 02/28/2012
• Status: Active Grant

• Current Assignee: Sipnose Ltd.
• Original Assignee: Sipnose Ltd.
• Inventors: Shahaf, Daniel, Shichor, Iris, Poran, Yehuda, Poran, Iftah
• Primary Examiner(s): Philips, Bradley H
• Assistant Examiner(s): Murphy, Victoria
• Application Number:
  US14/381,241
• Publication Number:
  US 20150297845A1
• Time in Patent Office: 2,532 Days
• CPC Class Codes: A61M 11/02 operated by air or other gas pressure applied to the liquid or other product to be sprayed or atomised sprayers for horticulture A01G, A01H; killing insects A01M; air humidifying by nozzles F24F6/14, F24F6/18; cooling by spraying F28B, F28C
• CPC Class Codes: A61M 15/0003 with means for dispensing more than one drug
• CPC Class Codes: A61M 15/0021 Mouthpieces therefor
• CPC Class Codes: A61M 15/0028 using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
• CPC Class Codes: A61M 15/0035 Piercing means
• CPC Class Codes: A61M 15/0045 using multiple prepacked dosages on a same carrier, e.g. blisters
• CPC Class Codes: A61M 15/009 using medicine packages with incorporated spraying means, e.g. aerosol cans pocket atomiser of the injector type A61M11/08
• CPC Class Codes: A61M 15/0091 mechanically breath-triggered
• CPC Class Codes: A61M 15/0093 without arming or cocking, e.g. acting directly on the delivery valve
• CPC Class Codes: A61M 15/0096 Hindering inhalation before activation of the dispenser
• CPC Class Codes: A61M 15/08 Inhaling devices inserted into the nose
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/073 Syringe, piston type
• CPC Class Codes: A61M 2205/3306 Optical measuring means
• CPC Class Codes: A61M 2205/3375 Acoustical, e.g. ultrasonic, measuring means
• CPC Class Codes: A61M 2205/581 by audible feedback
• CPC Class Codes: A61M 2205/583 by visual feedback
• CPC Class Codes: A61M 2205/584 having a color code
• CPC Class Codes: A61M 2205/7509 for virus
• CPC Class Codes: A61M 2205/7518 bacterial
• CPC Class Codes: A61M 2205/7545 : for solid matter, e.g. microaggregates
• CPC Class Codes: A61M 2206/14 : Static flow deviators in tubes disturbing laminar flow in tubes, e.g. archimedes screws
• CPC Class Codes: A61M 2210/0618 : Nose
• CPC Class Codes: A61M 2210/0625 : Mouth

Abstract

The present invention provides a two-step mechanism for delivering a flowable substance to the nasal passages, comprising: a. a nosepiece adapted to be in fluid connection with said nasal passages; b. at least one air-tight enclosure, comprising predetermined amount of compressed gas in the same; said compressed gas is pressurized to predetermined amount of pressure; c. a charging mechanism, fluidly connected with said air-tight enclosure, characterized by at least two configurations: a retracted position and an extended position; where, when said charging mechanism is transformed from said extended position to said retracted position, said charging mechanism is adapted to enable delivery of said pressurized and predetermined amount of compressed gas from at least one first predetermined position in said air-tight enclosure to at least one second predetermined position; d. an activation mechanism, adapted to entrain said flowable substance within said pressurized and predetermined amount of compressed gas.

Claims

1. A two-step mechanism for delivering a flowable substance to the nasal passages of a patient, said two-step mechanism comprising:

a. a nosepiece configured to be in fluid connection with said nasal passages;

b. an openable at least one air-tight enclosure, configured to contain a predetermined amount of gas;

said predetermined amount of gas compressible to a predetermined amount of pressure;

c. a charging mechanism, fluidly connected with said at least one air-tight enclosure, characterized by at least two configurations;

a retracted configuration and an extended configuration;

where, when said charging mechanism is transformed from said extended configuration to said retracted configuration, said charging mechanism is configured to enable delivery of said predetermined amount of gas from at least one first predetermined position in said at least one air-tight enclosure to at least one second predetermined position, said charging mechanism comprising a member of a group consisting of a piston drivable by a lever, an openable air-tight compartment preloaded with said predetermined amount of gas compressed to said predetermined amount of pressure, and any combination thereof; and

d. an activation mechanism, configured, upon activation, to release said predetermined amount of gas compressed to said predetermined amount of pressure from said at least one second predetermined position so as to entrain said flowable substance within said predetermined amount of gas and to deliver the same from said at least one second predetermined position to said nasal passages, said activation mechanism comprising a gas release mechanism selected from a group consisting of a valve mechanism, an air flow regulator, a rod configured to pierce the air-tight compartment, a spear configured to pierce the air-tight compartment, a needle configured to pierce the air-tight compartment, a knife configured to pierce the air-tight compartment, and any combination thereof;

wherein said two-step mechanism additionally comprises a mouthpiece connected to said charging mechanism;

said mouthpiece connected to said activation mechanism;

said activation being by application of suction to said activation mechanism through said mouthpiece.

2. The two-step mechanism of claim 1, wherein said flowable substance is deliverable to a member of a group consisting of respiratory epithelium, olfactory epithelium, brain, lungs, pharynx, heart and any combination thereof through said nasal passages.

3. The two-step mechanism of claim 1, wherein at least one of the following is being held true (a) said predetermined amount of gas is in a volume in a range of about 5-50 ml and said predetermined amount of pressure is in a range of 1.5-10 bar;

(b) said two-step mechanism additionally comprises at least one flowable substance container configured to contain said flowable substance, said at least one flowable substance container in fluid connection with said charging mechanism and said nosepiece;

(c) said transformation from said extended configuration to said retracted configuration is performed by applying pressure on said charging mechanism;

(d) said flowable substance comprises a medicament;

(e) when said charging mechanism is transformed from said retracted configuration to said extended configuration, said charging mechanism is configured to transfer said gas into said at least one first predetermined position; and

(f) said flowable substance is selected from a group consisting of a liquid, a powder, an aerosol, a slurry, a gel, a suspension and any combination thereof; and

any combination thereof.

4. The two-step mechanism of claim 1, wherein said charging additionally comprises a catch, a button, a predetermined sound pattern, a predetermined light pattern, slider, rotatable knob, a latch and any combination thereof.

5. The two-step mechanism of claim 1, wherein at least one of the following is being held true (a) said flowable substance is contained within at least one flowable substance container reversibly emplaceable within said two-step mechanism;

(b) said piston sealingly contained in a shaft, said piston flexibly connected to said lever, and said shaft fluidly connected to said openable air-tight enclosure;

(c) said shaft comprises said openable air-tight enclosure; and

(d) said nosepiece is configured to be removably emplaced in juxtaposition with a nostril, in a manner selected from a group consisting of sealingly emplaced within the nostril, sealingly emplaced against an opening of the nostril, loosely emplaced within the nostril, loosely emplaced against the opening of the nostril; and

(f) said charging mechanism comprises a filter, said filter configured to remove from the predetermined amount of gas at least one selected from a group consisting of particulates, bacteria, viruses, moisture, and undesired particles; and

any combination thereof.

6. The two-step mechanism of claim 1, wherein at least one of the following is being held true:

(i) said at least two configurations of said charging mechanism comprise three configurations, (a) a first configuration being said retracted, (b) a second configuration wherein said charging mechanism is partly extended, at least one flowable substance container is lockable in position and charging is initiatable, and (c) a third configuration being said extended configuration, wherein said at least one flowable substance container is insertable;

(ii) said at least one flowable substance container comprises a cartridge, said cartridge comprising a plurality of independently-openable containers, each said independently-openable container comprising a member of a group selected from (a) a single dose of said flowable substance, (b) multiple doses of said flowable substance, (c) different flowable substances, (d) said flowable substance, (e) carrier and (f) any combination thereof; and

(iii) said at least one flowable substance container comprises a filter, said filter upstream of said flowable substance, said filter configured to remove from the predetermined amount of gas at least one selected from a group consisting of particulates, bacteria, viruses, moisture, and undesired particles; and

any combination thereof.

7. The two-step mechanism of claim 1, wherein at least one of the following is being held true (a) said charging mechanism is configured to open at least one flowable substance container;

(b) said charging mechanism is configured to open said at least one flowable substance container during at least some portion of the time during which said charging mechanism is transformed from said extended configuration to said retracted configuration;

(c) said charging mechanism is configured to open said at least one flowable substance container at the beginning of the time during which said charging mechanism is transformed from said extended configuration to said retracted configuration;

(d) said at least one flowable substance container contains a single dose of said flowable substance; and

any combination thereof.

8. The two-step mechanism of claim 1, wherein at least one of the following is being held true (a) at least a portion of said mouthpiece is a member of a group consisting of removable, replaceable and any combination thereof;

(b) said mouthpiece comprises an auxiliary air filter, said filter configured to remove from gas passing through said filter at least one selected from a group consisting of particulates, bacteria, viruses, moisture, and undesired particles;

(c) said mouthpiece is in fluid connection with said valve mechanism within said two-step mechanism such that suction on said mouthpiece opens said valve mechanism, thereby enabling flow of said predetermined amount of gas compressed to said predetermined pressure through said two-step mechanism; and

(d) said activation mechanism comprises a hollow flexible tegument, wherein compressing and releasing said tegument opens said valve mechanism, thereby enabling flow of said predetermined amount of gas through said two-step mechanism; and

any combination thereof.

9. The two-step mechanism of claim 1, wherein at least one of the following is being held true (a) at least one flowable substance container comprises a plurality of compartments;

(b) said flowable substance comprises a first flowable substance and a second flowable substance;

least one of said compartments contains said second flowable substance different from said first flowable substance in at least one other of said compartments; and

any combination thereof.

10. The two-step mechanism of claim 1, wherein at least one of the following is being held true (a) said two-step mechanism is configured for a predetermined target population;

(b) said predetermined target population is persons of limited physical strength;

(c) delivery factors configured to provide optimum delivery of said flowable substance are selected from a group consisting of a length of time over which the delivery occurs, a gas speed in the nostril during delivery of the predetermined amount of gas with said entrained flowable substance, a volume of the predetermined amount of gas entering the nostril, an excess gas pressure in the nostril, a presence of turbulence in the region of the flowable substance, an absence of turbulence in the region of the flowable substance, a presence of turbulence in air channels within the two-step mechanism, an absence of turbulence in air channels within the two-step mechanism, a presence of turbulence in the nostril, an absence of turbulence within the nostril, a presence of turbulence in the nasal passages, an absence of turbulence in the nasal passages, and any combination thereof;

(d) parameters selected from a group consisting of a size of the at least one second predetermined position, travel of the piston, frictional force between a piston seal and the at least one air-tight enclosure, diameters of air channels within the two-step mechanism, a diameter of an inlet opening, a diameter of an outlet opening, a mass of the predetermined amount of gas, a volume within which the predetermined amount of gas is contained are configured to ensure optimum delivery of said flowable substance to a predetermined location in said nasal passages; and

(e) said predetermined location is selected from a group consisting of lower turbinates, middle turbinates, upper turbinates, ethmoid bone, and any combination thereof; and

any combination thereof.

11. The two-step mechanism of claim 1, wherein at least one of the following is being held true (a) said two-step mechanism additionally comprises indicating means configured to provide an indication to the user if said entrainment of said flowable substance within said predetermined amount of gas, and said delivery of said flowable substance entrained within said predetermined amount of gas from said two-step mechanism to said nasal passages has been successful;

wherein said indication is visible by means of a change of color, audible by means of a predetermined sound pattern and any combination thereof;

(b) said predetermined amount of gas is inert and will not react with said flowable substance;

(c) said flowable substance is a medicament selected from a group consisting of saline, an opioid, an agonist, an agonist-antagonist, an antagonist, an antitussive, an antiepileptic, an antipsychotic, a neuroleptic, a sedative-hypnotic, an anxiolytic agent, a centrally-acting muscle relaxant, a steroid, a corticosteroid, fluticasone propionate, olopatadine hydrochloride, Beclomethasone dipropionate, antihistamine, azelastine hydrochloride, xylometazoline hydrochloride, levocabastine hydrochloride, fluticasone furoate, mometasone furoate monohydrate, triamcinolone acetonide, calcitonin-salmon, calcitonin-salmon [rDNA origin], butorphanol tartrate, sofalcone, a combination of Influenza Virus H1N1 Influenza Virus H3N2 Influenza virus Victoria and Influenza virus Yamagata, fentanyl citrate, calcitonin, parathyroid hormone, a neurotransmitter, a neuromodulator, acetylcholine (ACH), an anticholinergic drug, adenosine triphosphate (ATP), aspartate (Asp), beta-amyloid, beta-endorphin, bradykinin, dopamine (DA), L-DOPA, epinephrine, a dynorphin, an endomorphin, an enkephalin, 5-hydroxytryptamine (5-HT), sumatriptan, dihydroergotamine mesylate, zolmitriptan, Gamma-aminobutyric acid (GABA), glutamate (glu), glycine, histamine, leptin, nerve growth factor, norepinephrine, nitric oxide, Substance P, alfentanil, desflurane, enflurane, etomidate, fentanyl, halothane, isoflurane, ketamine, methohexital, methoxyflurane, midazolam, morphine, nitrous oxide (N₂O), propofol, sevoflurane, sufentanil, thiopental, benzocaine, bupivacaine, cocaine, lidocaine, prilocaine, procaine, ropivacaine, tetracaine, codeine, diphenoxylate, heroin, hydrocodone, 1-alpha-acetyl-methadol, levomethadyl acetate, loperamide, meperidine, methadone, oxycodone, d-propoxyphene, a combination of at least one opioid with acetaminophen and asa, tramadol, buprenorphine, butorphanol, nalbuphine, nalorphine, naloxone, naltrexone, nalmefene, pentazocine, dextromethorphan, hydrocodone, amantadine, apomorphine, baclofen, a benzodiazepine, benztropine, bromocriptine, cyclobenzaprine, dantrolene, entacapone, haloperidol, pergolide, pramiprexole, ropinirole, trihexyphenidyl, rasagiline, ladostigil, rotigotine, monoamine oxidase inhibitor, Catechol-O-methyl transferase (COMT) inhibitor, acetazolamide, carbamazepine, clonazepam, diazepam, ethosuximide, felbamate, gabapentin, lamotrigine, lorazepam, phenobarbital, phenytoin, primidone, tiagabine, topiramate, valproic acid, vigabatrin, amitriptyline, bupropion, citalopram, clomipramine, desipramine, fluoxetine, fluvoxamine, imipramine, nortriptyline, paroxetine, phenelzine, sertraline, trazodone, tranylcypromine, venlafaxine, lithium carbonate chlorpromazine (CPZ), clozapine, fluphenazine, haloperidol, olanzapine, quetiapine, risperidone, sertindole, thioridazine, thiothixene, ziprasidone, alprazolam, chloral hydrate, diphenhydramine, flumazenil, flurazepam, hydroxyzine, oxazepam, temazepam, triazolam, zaleplon, zolpidem, chlorazepate, chlordiazepoxide, flumazenil, amphetamine, caffeine, ephedrine, methamphetamine, methylphenidate, phentermine, sibutramine, disulfiram, ethanol, methanol, atropine, scopolamine, ketamine, lysergic acid diethylamide (LSD), methylene dioxy-methyl amphetamine (MDMA), mescaline, phencyclidine (PCP), dronabinol, marijuana, Tetrahydrocannabinol (THC), nicotine, pentobarbital, davunetide, methylphenidrate, donepezil, galantamine, rivastigmine, tacrine, insulin, insulin detemir, insulin-like hormone, dopamine agonist, dopamine antagonist and any combination thereof.

12. A method for delivering a flowable substance to the nasal passages of a patient, comprising steps of:

i. providing a two-step mechanism for delivering said flowable substance to the nasal passages, said two-step mechanism comprising;

1. a nosepiece configured to be in fluid connection with said nasal passages;

2. an openable at least one air-tight enclosure, configured to contain a predetermined amount of gas;

said predetermined amount of gas compressible to a predetermined amount of pressure;

3. a charging mechanism fluidly connected with said at least one air-tight enclosure, characterized by at least two configurations;

a retracted configuration and an extended configuration;

where, when said charging mechanism is transformed from said extended configuration to said retracted configuration, said charging mechanism is configured to deliver said predetermined amount of gas from at least one first predetermined position in said at least one air-tight enclosure to at least one second predetermined position;

said charging mechanism comprising a member of a group consisting of a piston drivable by a lever, an openable air-tight compartment containing said predetermined amount of gas compressed to said predetermined amount of pressure, any combination thereof; and

,

4. an activation mechanism, configured, upon activation, to release said predetermined amount of gas compressed to said predetermined amount of pressure from said at least one second predetermined position so as to entrain said flowable substance within said predetermined amount of gas and to deliver the same from said at least one second predetermined position to said nasal passages, said activation mechanism comprising a gas release mechanism selected from a group consisting of a valve mechanism, an air flow regulator, a rod configured to pierce the air-tight compartment, a spear configured to pierce the air-tight compartment, a needle configured to pierce the air-tight compartment, a knife configured to pierce the air-tight compartment, and any combination thereof;

ii. providing said flowable substance, contained within a container;

iii. fluidly connecting said container with said charging mechanism and said nosepiece;

iv. charging said two-step mechanism by transforming said charging mechanism from said extended configuration to said retracted configuration;

thereby delivering said predetermined amount of gas from at least one first predetermined position in said at least one air-tight enclosure to at least one second predetermined position;

v. emplacing said nosepiece in juxtaposition with a nostril in fluid connection with said nasal passages; and

vi. activating said two-step mechanism;

thereby entraining said flowable substance within said predetermined amount of gas and delivering the same from said at least one second predetermined position to said nasal passages

wherein said two-step mechanism additionally comprises a mouthpiece connected to said charging mechanism;

said mouthpiece connected to said activation mechanism;

said activation being by application of suction to said activation mechanism through said mouthpiece.

13. The method of claim 12, additionally comprising a step of configuring said two-step mechanism to provide said predetermined amount of gas in volumes of about 5-50 ml and compressed to about 1.5-10 bar.