More specifically, and as shown in FIGS. 1-2 and 9-10, single-directional insufflator or breath-powered nasal device 10 of the present invention comprises nose guard 20, dual wall drug dispensing system 30, mesh disc 40 on which drug 200 (not shown) is positioned, first tube connector 60, corrugated tubing 80, second tube connector 70, ridge connector 110, one-way valve mouth piece 100 housing a one-way valve 50 (not shown) in bottom section 103 that directs airflow in one direction and prevents reverse airflow direction, so that, first air-flow directional indicator band 160 and second air-flow directional indicator band 170, when single-directional insufflator or breath-powered nasal device 10 is in use and seal cap 150, i.e., top cover, is removed and user blows air through the one-way vale mouth piece 100, drug 200 (not shown) positioned on mesh disc 40 is propelled out of nose guard 20.

As further shown in FIGS. 9-10, the top end portion 31 of the dual wall drug dispensing system 30 is press-fit through bottom 26 of through-hole 24 of nose guard 20 and positioned snugly against nose guard seat 22 located near top 25 of through-hole 24 of nose guard 20. The bottom end portion 32 of the dual wall drug dispensing system 30 is press-fit into first top hollow collar 65 of first tube connector 60 to form a tight seal there between. Mesh disc 40 is inserted into and sits on top of first seat 61 located at the bottom of first top hollow collar 65 of first tube connector 60. First bottom hollow neck 66 of first tube connector 60 is press-fit into the first hollow cuff 81 of corrugated tubing 80 to form a tight seal there between. Second bottom hollow neck 76 of second tube connector 70 is press-fit into the second hollow cuff 82 of corrugated tubing 80 to form a tight seal there between. Bottom section 102 of one-way valve mouth piece 100 is press-fit into second top hollow collar 75 of second tube connector 70 until it is resting on second seat 71 of second tube connector 70 to form a tight seal there between.

Thus, and as further shown in FIGS. 9-10, one-way valve 50 (not shown) housed in bottom section 103 of one-way valve mouth piece 100 directs air-flow in one direction (prevents reverse air-flow direction) through (a) conduit 101 in one-way valve mouth piece 100, (b) second bottom hollow neck 76 of second tube connector 70, (c) corrugated tubing 80, (d) first bottom hollow neck 66 of first tube connector 60 and mesh disc 40 sitting on first seat 61 in first tube connector 60, (e) inner and outer hollow chambers 33a and 33b of dual wall drug dispensing system 30 that create novel inner and outer air-flows in which drug substance 200 is concentrated within and propelled by the inner air-flow and the outer air-flow surrounds the inner air-flow to concentrate drug substance 200 within inner air-flow as it exits top end portion 31 of inner hollow chamber 33a and top 25 of through-hole 24 (not shown) of nose guard 20, so that drug substance 200, when breath-powered, is propelled from the novel, single-directional insufflator or breath-powered nasal device 10 meshmeshmeshmesh within a novel and unique double air-flow in a vertical, somewhat tight or confined and narrow, concentrated plume in high drug concentration, i.e., the inner air-flow, deep into the superior nasal cavity for effective distribution into the olfactory region and the mucosa innervated by the trigeminal nerve and for direct diffusion therefrom into the brain that is driven by the blown air through the novel, the single-directional insufflator or breath-powered nasal device 10.

As depicted in FIGS. 7-8, a bridge connector 110 connects one side 131 of the novel, the single-directional insufflator or breath-powered nasal device 10 comprising the one-way valve mouth piece 100 and the second tube connector 70 to the other side 131 of the novel, the single-directional insufflator or breath-powered nasal device 10 comprising the nose guard 20, the dual wall drug dispensing system 30, the mesh disc 40 and the first tube connector 60 to maintain breath-powered insufflator or breath-powered nasal device 10 of the present invention in a “U-shape”configuration 140. Bridge connector 110 comprises bridge connector 110 sandwiched between a first hollow ring 122 and a second hollow ring 123 for sliding over the first hollow cuff 81 and second hollow cuff 82 of corrugated tubing 80. See FIGS. 15-16 and 18-19.

Alternatively, and as shown FIGS. 13-14, bridge connector 110 affixed to single-directional insufflator or breath-powered nasal device 10, illustrated in front view 135 with nose guard side 130 and one-way valve mouth piece side 131, may be designed with a perforation or score line 124 or any other configuration that allows bridge connector 110 to be broken and separated into two individual pieces in the event sides 130 and 131 of breath-powered insufflator or breath-powered nasal device 10 need to be orientated or adjusted at a different angle for use by, for example, a concussed person, or a second person who is assisting a person who, for example, is a concussed person, who cannot self-administer the necessary blow force to provide sufficient airflow to effectively propel the drug substance from the single-directional insufflator or breath-powered nasal device 10 of the present invention to effectively treat the concussion with the drug substance, as shown in FIG. 12.

Dual wall drug dispensing system 30, i.e., Dual-walled tubing configuration, is a novel and unique delivery system for delivering one or more drug substances into the nasal cavity. The dual wall drug dispensing system 30 comprises a top end portion 31 and the bottom end portion 32 and two hollow chambers 33, an inner hollow chamber 33a and an outer hollow chamber 33b. The drug substance 200 is propelled through hollow inner chamber 33a when the breath-powered insufflator or breath-powered nasal device 10 of the present invention is breath propelled. The hollow outer chamber 33b, which surrounds the hollow inner chamber 33a, is divided into two, three, four or more separate chambers 34 by rib walls 35. Preferably, but not necessarily critical, hollow outer chamber 33b is divided into three separate chambers 34. In addition to providing multiple hollow chambers 34, rib walls 35 impart integrity, structure and strength to and support for dual wall drug dispensing system 30.

While the present invention contemplates dual chamber 34 comprised of inner hollow chamber 33a and outer hollow chamber 33b of the dual wall drug dispensing system 30, i.e., Dual-walled tubing configuration, can be of any suitable dimensions necessary to perform effectively the objectives of the present invention, it is preferred that inner hollow chamber 33a can accommodate up to about 120 mg or more and any amount there between of drug substance in dry powder or other form and its outer wall diameter 331 can range from, for example, about 3 mm to about 7 mm or more or less and its inner wall diameter 332 can range from about 2 mm to about 5 mm or more or less, and outer wall diameter 333 can range from, for example, about 9 mm to about 13 mm or more or less and its inner wall diameter 334 can range from about 7 mm to about 12 mm or more or less.

Preferably, and by way of example, as shown in FIG. 29, one inner hollow chamber 33a contemplated by the present invention is dimensioned with an outer wall 331 diameter of about 5 mm and an inner wall 332 diameter of about 3 mm creating an internal gap 37 diameter of inner hollow camber 33a of about 3 mm. While these exemplary diameter dimensions generate about a 3 mm internal gap 37 between outer wall 333 of inner hollow chamber 33a and inner wall 334 of outer hollow chamber 33b, the present invention also contemplates inner hollow chambers 33a designed with an internal gap 37 diameter of up to about 1 mm to about 4 mm or greater. Thus, in accordance with the present invention, and preferably, internal gap 37 diameters may range from about 1 mm to about 4 mm or more, including internal gap 37 diameters of about 1 mm, about 1.5 mm, about 2 mm, about 2.5 mm, about 3 mm, about 3.5 mm and about 4 mm and dimension sizes there between, so that nose guard 20 can of a size that it allows nose guard 20 can be sized to snuggly accommodate any size nostril as discussed herein before.

While the thicknesses of outer wall 331 and inner wall 332 of inner hollow chamber 33a and outer wall 333 and inner wall 334 of outer hollow chamber 33b may be of any suitable thickness, it is preferred that the actual thickness of walls, 331, 332 and 333, 334 of the dual wall drug dispensing system 30, i.e., dual-walled tubing configuration, is about 2 mm thick.

To load the drug substance 200, when in a powdered, spray-dried format, into a novel single-directional insufflator or breath-powered nasal device 10 of the present invention, a sterilized funnel (not shown) is used to load the powdered drug substance 200 specifically within inner hollow chamber 33a of dual wall drug dispensing system 30. The mesh disc 40, which is positioned at bottom end portion 32 of inner hollow chamber 33a and on first seat 61 of first tube connector as shown in FIGS. 9-10 and 23, is what the loaded powdered drug substance 200 first encounters and against which it rest once fully loaded. Because the pore size of mesh disc 40 is smaller than the particle size of the powdered drug substance, the powdered drug substance cannot fall through mesh disc 40. The pores throughout mesh disc 40, however, permit the blown airflow to penetrate up and through mesh disc 40 to carry and propel powdered drug substance 200 through the inner hollow chamber 33a of dual wall drug dispensing system 30, i.e., the double walled-tube configuration, and top 25 of through-hole 24 and out of nose guard 20 deeply into the nasal cavity. It should be understood that if a liquid, suspension, gel or the like is loaded into dual wall drug dispensing system 30, i.e., the double walled-tube configuration, a different mesh disc 40 that prevents leakage or seepage there through may be warranted.

Preferably, the particle size distribution of powdered, spray-dried, drug substance 200 is principally in the range of about 1 μm to about 10 μm or more. In one embodiment, the powdered, spray-dried, drug substance 200 contains a medicament, particularly for the treatment of a nasal condition. Notwithstanding the preferred particle size, the present invention contemplates any effective particle size distribution of a powdered, spray-dried, drug substance that will accomplish the objectives of the present invention, including larger particles, or a smaller fraction of larger particles, typically in the range of about 10 μm to about 30 μm, and preferably in the range of about 20 μm to about 30 μm.

Turning now to operation, when a person blows or exhales through mouth piece 100 of the single-directional insufflator or breath-powered nasal device 10 of the present invention, as shown in FIGS. 11 and 12, the blown air flows through both hollow chambers 33a and 33b of dual wall drug dispensing system 30, i.e., the double walled-tube configuration, simultaneous and with essentially the same force expelling the drug substance loaded into inner hollow chamber 33a from nose guard 20. The air-flow pressure exiting from outer hollow chamber 33b surrounds the airflow burdened with high drug substance concentration exiting from inner hollow chamber 33a forcing the drug substance loaded air-flow to travel at least initially in a vertical, somewhat tight or confined and narrow, concentrated plume carrying high drug substance concentration into the deepest part of the superior nasal cavity, namely, the olfactory region and nerve and the mucosa innervated by the trigeminal nerve for direct diffusion therefrom into the brain. Thus, novel dual wall drug system 30, i.e., a dual wall-tube configuration, uniquely and surprisingly delivers high drug substance concentration to the targeted olfactory region, even the mucosa innervated by the trigeminal nerve, for direct diffusion into the brain for effective treatment of CNS injury, disease and/or disorders, including the brain, the brain stem, and the spinal cord and, in particular TBI, especially concussion.

While it should now be appreciated that the unique design of the single-directional insufflator or breath-powered nasal device 10 of the present invention uniquely targets drug deposition at and into the olfactory region and the trigeminal nerve mucosa for direct diffusion into the brain, the initial flow pattern of the exiting drug substance loaded airflow may fan out to some extent causing some drug substance to be deposited on other parts of the nasal cavity. It should be further appreciated that, while it is preferred to load only the inner hollow chamber 33a with drug substance 200, different or same drug substance(s) may be loaded into the two or more separate chambers 34 of outer hollow chamber 33b for deposition of drug substance(s) throughout the nasal cavity to treat CNS and nasal cavity and other nasal disorders treated via nasal application.

Thus, the present invention is uniquely suited to treat local, systemic and CNS injuries and/or disorders. It should be understood, however, that the single-directional insufflator or breath-powered nasal device 10 of the present invention is preferably a single use, disposable device especially designed to treat TBI, preferably mild, moderate and severe TBI, more preferably, mild to moderate TBI, even more preferably mild TBI, and most preferably, concussion. An example of drug substances suitable for use in combination with the single-directional insufflator or breath-powered nasal device 10 are C-20 steroid compounds in dry powder, spray-dried form, as disclosed and described in U.S. Patent Publication No. 2016/0168190, entitled “C-20 steroid compounds, compositions and uses thereof,” and WO2016/044559A1, entitled “C-20 steroid compounds, compositions and uses thereof to treat traumatic brain injury (TBI), including concussions,” each of which is incorporated herein by reference in its entirety as if it was fully set forth herein. One preferred C-20 steroid compound that is contemplated by the present invention is ent-19-norprogesterone in dry-powder, spray-dried form. Ent-19-norprogesterone has a molecular formula of C₂₀H₂₈O₂and a molar mass of 300.435 g/mol. One chemical name for ent-19-norprogesterone is ent-19-norpregn-4-ene-3,20-dione. The chemical structure of ent-19-norprogesterone is as follows:

[Image Omitted]

ent-19-norprogesterone is a fully synthetic, non-naturally, occurring neurosteroid. In preclinical studies, ent-19-norprogesterone has demonstrated equivalent, if not superior, neuroprotective effects compared to related neurosteroids. Animal models of concussion demonstrated that ent-19-norprogesterone reduces the behavioral pathology associated with brain injury symptoms such as memory impairment, anxiety, and motor/sensory performance. Additionally, ent-19-norprogesterone is lipophilic and can easily cross the blood-brain barrier to rapidly eliminate or at least reduce swelling, oxidative stress and inflammation in the brain while the healing process from TBI, e.g., concussion, attempts to restore proper blood flow and heal damaged or affected brain and/or other tissue.

When ent-19-norprogesterone is the drug substance of choice to treat TBI, especially concussion, inner hollow chamber 33a is pre-loaded in accordance with the present invention with preferably about 100 mg of drug substance ent-19-norprogesterone, wherein the ent-19-norprogesterone drug substance comprises about 8 mg and the pharmaceutical acceptable excipient, hydroxypropyl-ß-cyclodextrin, comprises about 92 mg. This 19-norprogesterone formulation is preferably in dry-powder, spray-dried format and can be administered up to four or more times a day for as long as necessary in accordance with a prescribed treatment regimen to treat, for example, a patient suffering with TBI, especially a concussion. To administer ent-19-norprogesterone drug substance preloaded into inner hollow chamber 33a of the dual wall drug dispensing system 30 of the single-directional insufflator or breath-powered nasal device 10 of the present invention, the concussed or TBI injured person inserts nose guard 20 into one nasal vestibule or nostril until it is snug-fitting and then inserts mouth piece 100 between his/her lips. Once the single-directional insufflator or breath-powered nasal device 10 of the present invention is properly fitted in the nostril and between the lips of the concussed or TBI injured person, the concussed or TBI injured patient blows/exhales through mouth piece 100: (a) to close the velum or soft palate to isolate the nasal cavity to prevent the ent-19-norprogesterone drug substance from being inhaled or passing into the digestive system and therefore reducing systemic side effects; and (b) to propel the ent-19-norprogesterone drug substance in the inner hollow chamber 33a from the nose guard 20 with sufficient airflow force and pressure, that concentrated ent-19-norprogesterone drug substance is deposited onto and distributed throughout the olfactory region and the trigeminal nerve mucosa for direct diffusion into the brain for effective treatment of the concussion or TBI within minutes of nasal application. Importantly, one-way valve mouth piece 100 prevents reverse air-flow and the closed soft palate will trap the concentrated ent-19-norprogesterone drug in the nasal cavity allowing it to stick to the superior nasal membranes for diffusion directly into the brain by way of the olfactory nerve and the trigeminal nerve mucosa.

This very advantageous and unique nasal delivery is accomplished by the novel dual wall drug dispensing system 30, i.e., the double walled-tube configuration, of the single-directional insufflator or breath-powered nasal device 10 of the present invention through the use of the unique dual air-flow combination of (i) a first air-flow expelled from the inner hollow chamber 33a carrying the ent-19-norprogesterone drug substance, and (ii) a second air-flow expelled simultaneously from the outer hollow chamber 33b to create air-flow pressure that surrounds the first expelled air-flow, so that the first expelled air flow forms and travels initially in a vertical, somewhat tight or confined and narrow, concentrated plume that drives a concentrated drug substance, e.g., ent-19-norprogesterone drug substance, to the targeted olfactory region, including the olfactory nerve, and the trigeminal nerve mucosa for direct diffusion into the brain and for effective treatment of the concussion or TBI within minutes of nasal application.

While single-directional insufflator or breath-powered nasal device 10 of the present invention is simple in construction, the operation of the device does provide for the effective delivery of drug substances, in particular one of powder containing the drug substance, to the posterior region of the nasal airway, since the powdered drug substance is delivered in a single-direction deep into the nasal cavity and the air-flow into the nasal cavity is through the same opening, namely, the respective nostril, with the closed posterior region of the respective nasal cavity acting as a pressure reflecting surface which causes the exhaled air to adequately reach the posterior region of the respective nasal cavity for deposition into the olfactory region and the trigeminal nerve mucosa for rapid diffusion into the brain for the treatment of nasal and/or CNS injury, disease or disorder, especially brain injury, such as TBI, including concussion. Further, in providing a short explosive burst of air-flow into one of the nasal cavities, it is now possible to achieve a sustained single-directional air-flow deep within the nasal cavity of high concentrated powdered drug substance, which is believed to be necessary to deliver a powdered drug substance effectively to the posterior region of the nasal airway for deposition into the olfactory region and the trigeminal nerve mucosa for rapid diffusion into the brain.

As contemplated by the present invention, any suitable materials may be used for the individual parts or components of the single-directional insufflator or breath-powered nasal devices 10 of the present invention, VESTAMID ML21 is an example of a selected material for plastic parts, e.g., dual wall drug dispensing system 30 and tube connectors 60 and 70. ABS is an exemplary material for mouth piece 100 and one-way valve 50 (not shown). PTFE is an exemplary material for corrugated tubing 80. Silicone HD-150A is exemplary material for nose guard 20, bridge connector 110 and seal cap 150, i.e., top cover.

In accordance with one embodiment of the present invention, the length of the dual wall drug dispensing system 30, i.e., the double walled-tube configuration, is about 2.00 inches and the length of the corrugated tube is about 4 inches. Total length of such an exemplary device is about 8 inches. When in U-shape configuration, the maximum length of such device is about 4 inches from the bottom of the corrugated material to the top of the nose guard 20 and the width is about 2.2 inches. The width of the corrugated material from side view is about 0.45 inches and the widest width of nose guard 20 is about 0.75 inches, as shown in FIG. 38, and the widest width of one-way valve mouth piece 100 is about 0.5 inches.

It should be further understood that the above summary of the present invention is not intended to limit or describe each and every possible embodiment or implementation of the present invention, but contemplates such possible embodiments and implementations. The description, however, does exemplify illustrative embodiments. In several places throughout the specification, guidance is provided through examples, which examples can be used in various combinations. In each instance, the examples serve only as representative groups and should not be interpreted as exclusive examples.

DESCRIPTION OF THE FIGS.

The structure, operation and advantages of this invention will become further apparent upon consideration of the following description, taken in conjunction with the accompanying Figs., wherein:

FIG. 1 is a front assembled elevational angled front view 135 of a single-directional insufflator or breath-powered nasal device 10, in accordance with an embodiment of the of the present invention;

FIG. 2 is a rear assembled elevational angled back view 136 of a single-directional insufflator or breath-powered nasal device 10, in accordance with an embodiment of the of the present invention;

FIG. 3 is a top view 850 of a corrugated tube 80 showing corrugated middle section 85 and bridge connector 110, in accordance with an embodiment of the of the present invention;

FIG. 4 is a bottom view 860 of a corrugated tube 80 showing corrugated middle section 85, in accordance with an embodiment of the of the present invention;

FIG. 5 is an assembled elevational view of nose guard side 130 of the single-directional insufflator or breath-powered nasal device, in accordance with an embodiment of the of the present invention;

FIG. 6 is an assembled elevational view of the one-way valve mouth piece side 131 of the single-directional insufflator or breath-powered nasal device, in accordance with an embodiment of the of the present invention;

FIG. 7 is a right mouth piece assembled elevational view of a single-directional insufflator or breath-powered nasal device, in accordance with an embodiment of the of the present invention;

FIG. 8 is a left mouth piece assembled elevational view of a single-directional insufflator or breath-powered nasal device, in accordance with an embodiment of the of the present invention;

FIG. 9 is a right mouth piece front unassembled exploded view of a single-directional insufflator or breath-powered nasal device, in accordance with an embodiment of the of the present invention;

FIG. 10 is a left mouth piece front unassembled exploded view of a single-directional insufflator or breath-powered nasal device, in accordance with an embodiment of the of the present invention;

FIG. 11 schematically illustrates a single-directional insufflator or breath-powered nasal device of FIGS. 1-2 and 4-8 inserted into a nasal cavity of a subject for operation, in accordance with an embodiment of the of the present invention;

FIG. 12 schematically illustrates a nose guard of an alternative embodiment of a single-directional insufflator or breath-powered nasal device as shown in FIGS. 13 and 14 inserted into a nasal cavity of a first subject to be treated with a drug substance and a mouth piece of the alternative embodiment as shown in FIGS. 13 and 14 inserted between the lips of a second subject for operation of the alternative embodiment by the second subject as shown in FIGS. 13 and 14, in accordance with an embodiment of the of the present invention;

FIG. 13 is a front, right mouth piece, assembled elevational angled view of an alternative embodiment of a single-directional insufflator or breath-powered nasal device herein wherein the bridge connector is designed with a perforated or score line for breaking the bridge connector, in accordance with an embodiment of the of the present invention;

FIG. 14 is a front, right mouth piece, assembled elevational angled view of an alternative embodiment of a single-directional insufflator or breath-powered nasal device herein wherein the bridge connector is broken in two pieces at the perforated or score line for breaking the bridge connector, as shown in FIG. 13, in accordance with an embodiment of the of the present invention;

FIG. 15 schematically illustrates assembling bridge connector 110 to corrugated tubing 80, in accordance with an embodiment of the of the present invention;

FIG. 16 schematically illustrates a perspective view of bridge connector 110 and corrugated tubing 80 assembled in accordance with an embodiment of the of the present invention;

FIG. 17 schematically illustrates a front view of bridge connector 110 and corrugated tubing 80 assembled in accordance with an embodiment of the of the present invention;

FIG. 18 schematically illustrates assembling first tube connector 60 and second tube connector 70 to corrugated tubing 80 assembled with bridge connector 110, as shown in FIGS. 16 and 17, in accordance with an embodiment of the of the present invention;

FIG. 19 schematically illustrates a perspective view of first tube connector 60 and second tube connector 70 assembled with corrugated tubing 80 assembled with bridge connector 110, as shown in FIGS. 16 and 17, in accordance with an embodiment of the of the present invention;

FIG. 20 schematically illustrates a cross-sectional view of a tube connector, in accordance with an embodiment of the of the present invention;

FIG. 21 schematically illustrates inserting a mesh disc 40 into first tube connector 60, wherein first tube connector 60 and second tube connector 70 are assembled with corrugated tubing 80 assembled with bridge connector 110, as shown in FIGS. 16 and 17, in accordance with an embodiment of the of the present invention;

FIG. 22 schematically illustrates inserting a dual wall drug dispensing system 30, i.e., a double-walled tube configuration, into first tube connector 60, wherein mesh disc 40 is inserted into first tube connector 60 and first tube connector 60 and second tube connector 70 are assembled with corrugated tubing 80 assembled with bridge connector 110, as shown in FIGS. 16, 17, 19 and 21, in accordance with an embodiment of the of the present invention;

FIG. 23 schematically illustrates an exploded cross-sectional view of assembled first tube connector 60, wherein mesh disc 40 and dual wall drug dispensing system 30, i.e., a double-walled tube configuration, are assembled within first tube connector 60 and mesh disc 40 is sitting on first seat 61 of first tube connector 60 and first top hollow collar 65 of first tube connector 60 is press-fit into first hollow cuff 81 of corrugated tubing 80, in accordance with an embodiment of the of the present invention;

FIG. 24 schematically illustrates inserting top end portion 31 of dual wall drug dispensing system 30, i.e., the double walled-tube configuration, into bottom 26 of through-hole 24 of nose guard 20, wherein mesh disc 40 is assembled within first tube connector 60 and first tube connector 60 and second tube connector 70 are assembled with corrugated tubing 80 assembled with bridge connector 110, as shown in FIGS. 16, 17, 19, 21 and 22, in accordance with an embodiment of the of the present invention;

FIG. 25 schematically illustrates a front view of assembled nose guard 20, first tube connector 60, mesh disc 40 (not shown), dual wall drug dispensing system 30, i.e., a double-walled tube configuration, first tube connector 60 and second tube connector 70, bride connector 110 and corrugated tubing 80, in accordance with an embodiment of the of the present invention;

FIG. 26 schematically illustrates placing seal cap 150 with seal cap plug 151 into top 25 (not shown) of through-hole 24 (not shown) over nose guard 20 of assembled nose guard 20, first tube connector 60, mesh disc 40 (not shown), dual wall drug dispensing system 30, i.e., a double-walled tube configuration, first tube connector 60 and second tube connector 70, bride connector 110 and corrugated tubing 80, in accordance with an embodiment of the of the present invention;

FIG. 27 schematically illustrates an exploded cross-sectional view of nose guard 20, wherein dual wall drug dispensing system 30, i.e., the double walled-tube, is inserted through through-hole 24 of nose guard 20, top end portion 31 of dual wall drug dispensing system 30, i.e., a double-walled tube configuration, is seated against nose guard seat 22 of nose guard 20 and seal cap 150 is positioned over nose guard 20 with nose guard stem 151 is inserted through top 25 and into through-hole 24 of nose guard 20, in accordance with an embodiment of the of the present invention;

FIG. 28 schematically illustrates inserting bottom section 102 of one-way valve mouth piece 100 into of dual wall drug dispensing system 30, i.e., the double walled-tube, into second top hollow collar 75 of second tube connector 70, assembled seal cap 150, nose guard 20, first tube connector 60, mesh disc 40 (not shown), dual wall drug dispensing system 30, i.e., a double-walled tube configuration, first tube connector 60 and second tube connector 70, bride connector 110 and corrugated tubing 80, in accordance with an embodiment of the of the present invention;

FIG. 29 is an exploded cross-sectional view of inner hollow chamber 33a, having outer wall 331 and inner wall 332, and outer hollow chamber 33b having outer wall 333 and inner wall 334 of dual wall drug dispensing system 30, i.e., a double-walled tube configuration, illustrating one size tube diameters, wherein, outer hollow chamber 33b having outer wall 333 diameter of 11 mm and inner wall 334 diameter of 9 mm and inner hollow chamber 33a having outer wall 331 diameter of 6 mm and inner wall 332 diameter of 4 mm with internal gap 36 of 1.5 mm and an inner hollow chamber 33a having an internal diameter of 4 mm. Illustrations of alternative size tube diameters are: (a) outer hollow chamber 33b having outer wall 333 diameter of 10 mm and inner wall 334 diameter of 8 mm and inner hollow chamber 33a having outer wall 331 diameter of 6 mm and inner wall 332 diameter of 4 mm with internal gap 36 of 1 mm and an inner hollow chamber 33a having an internal diameter of 4 mm; (b) outer hollow chamber 33b having outer wall 333 diameter of 11 mm and inner wall 334 diameter of 9 mm and inner hollow chamber 33a having outer wall 331 diameter of 5 mm and inner wall 332 diameter of 3 mm with internal gap 36 of 2 mm and an inner hollow chamber 33a having an internal diameter of 3 mm; and (c) outer hollow chamber 33b having outer wall 333 diameter of 13 mm and inner wall 334 diameter of 11 mm and inner hollow chamber 33a having outer wall 331 diameter of 5 mm and inner wall 332 diameter of 3 mm with an internal gap 36 of 3 mm and an inner hollow chamber 33a having an internal diameter of 3 mm, in accordance with various embodiments of the of the present invention;

FIG. 30 is a perspective view of dual wall drug dispensing system 30, i.e., a double-walled tube configuration, bottom end portion 32, internal gap 36 and the two hollow chambers 33, i.e., the inner hollow chamber 33a and the outer hollow chamber 33b, wherein the outer hollow chamber 33b is divided into three separate chambers 34 by rib walls 35, in accordance with an embodiment of the of the present invention;

FIG. 31 is a cross-sectional view of dual wall drug dispensing system 30, i.e., a double-walled tube configuration, as shown in FIGS. 9, 10, 19 and 30, in accordance with an embodiment of the of the present invention;

FIG. 32 is a cross-sectional view taken along line A of dual wall drug dispensing system 30, i.e., a double-walled tube configuration, as shown in FIGS. 9, 10, 19, 30 and 31, in accordance with an embodiment of the of the present invention;

FIG. 33 is a cross-sectional view of tube connector 60 or 70 taken along line A, as shown in FIGS. 9, 10, 18, 23 and 31, in accordance with an embodiment of the of the present invention;

FIG. 34 is a cross-sectional view of tube connector 60 or 70, as shown in FIGS. 9, 10, 18, 23 and 31, in accordance with an embodiment of the of the present invention;

FIG. 35 is a cross-sectional view of nose guard 20 taken along line A depicting top 25 of through-hole 24, as shown in FIGS. 9, 10, 24, 25 and 27, in accordance with an embodiment of the of the present invention;

FIG. 36 schematically illustrates an alternative cross-sectional view of nose guard 20, depicting top 25 and bottom 26 of through-hole 24 and nose guard seat 22, as shown in FIGS. 9, 10, 24, 25, 27 and 35, in accordance with an embodiment of the of the present invention;

FIG. 37 schematically illustrates an assembled view of single-directional insufflator or breath-powered nasal device 10 depicting one-way valve mouth piece 100, first air-flow directional band 160, first tube connector 60, corrugated tubing 80, bridge connector 110, second tube connector 70, second air-flow directional band 170, dual wall drug dispensing system 30 and nose guard 20, in accordance with an embodiment of the of the present invention;

FIG. 36 schematically illustrates an alternative one-way valve mouth piece 131 view of and assembled single-directional insufflator or breath-powered nasal device 10 nose guard, as shown in FIG. 6, in accordance with an embodiment of the of the present invention;

FIG. 39 schematically illustrates an unassembled view of seal cap 150, i.e., top plug, nose guard 20, one-way valve dual wall drug dispensing system 30, i.e., a double-walled tube configuration, mesh disc 40, and alternative connector 180 for connecting one-way dual wall drug dispensing system 30, i.e., the double walled-tube, and corrugated tubing 80, in accordance with an embodiment of the of the present invention;

FIG. 40 schematically illustrates an alternative cross-sectional view of seal cap 150, i.e., top plug, nose guard 20, and one-way valve dual wall drug dispensing system 30, i.e., a double-walled tube configuration, assembled with alternative connector 180, as shown in FIG. 39, in accordance with an embodiment of the of the present invention;

FIG. 41 schematically illustrates an assembled front view of nose guard 20, dual wall drug dispensing system 30, i.e., a double-walled tube configuration, alternative connector 180, corrugated tubing 80, and nose guard 20, in accordance with an embodiment of the of the present invention;

FIG. 42 schematically illustrates a top view of a tray packaged with twenty single-directional insufflator or breath-powered nasal fully assembled devices herein, wherein the 20 such devices are positioned in two rows of five pairs of such devices, wherein each such pair shows two such devices positioned in an interlocking position with respect to one another, in accordance with an embodiment of the of the present invention;

FIG. 43 schematically illustrates a side top view of a tray packaged exposing an internal side longitudinal wall with twenty single-directional insufflator or breath-powered nasal fully assembled devices herein, wherein the 20 such devices are positioned in two rows of five pairs of such devices, wherein each such pair shows two such devices positioned in an interlocking position with respect to one another, in accordance with an embodiment of the of the present invention;

FIG. 44 illustrates a screen shot comparing the width of a lactose powder spray between a single tube configuration and a dual wall drug dispensing system 30, i.e., a double-walled tube configuration, of the present invention in which the internal diameter of the inner tube of the double tube is about 4 mm and the gap between the inner and outer tubes of the double tube is either 1.5 mm or 1 mm to a single tube configuration, as compared to baseline, i.e., a single tube configuration, in accordance with an embodiment of the of the present invention;

FIG. 45 illustrates a screen shot comparing the width of a lactose powder spray between a single tube configuration and a dual wall drug dispensing system 30, i.e., a double-walled tube configuration, of the present invention in which the internal diameter of the inner tube of the double tube is about 3 mm and the gap between the inner and outer tubes of the double tube is either 2 mm or 3 mm to a single tube configuration, as compared to baseline, i.e., a single tube configuration, in accordance with an embodiment of the of the present invention;

FIG. 46 is a screen shot of a single tube configuration with a 3 mm baseline following a lactose powder spray showing significant build up or accumulation of lactose powder on internal wall post-powder spray;

FIG. 47 is a screen shot of a single tube configuration with a 4 mm baseline following a lactose powder spray showing significant build up or accumulation of lactose powder on internal wall post-powder spray;

FIG. 48 is a screen shot of a dual wall drug dispensing system 30, i.e., a double-walled tube configuration, with a 1 mm gap following a lactose powder spray showing little build up or accumulation of lactose powder on inner wall 332 of inner hollow chamber 33a post-powder spray, as compared to the single tube configuration as shown in FIG. 45, in accordance with an embodiment of the of the present invention;

FIG. 49 is a screen shot of a dual wall drug dispensing system 30, i.e., a double-walled tube configuration, with a 1.5 mm gap following a lactose powder spray showing little build up or accumulation of lactose powder on inner wall 332 of inner hollow chamber 33a post-powder spray, as compared to the single tube configuration as shown in FIG. 45, in accordance with an embodiment of the of the present invention;

FIG. 50 is a screen shot of a dual wall drug dispensing system 30, i.e., a double-walled tube configuration, with a 2 mm gap following a lactose powder spray showing little build up or accumulation of lactose powder on inner wall 332 of inner hollow chamber 33a post-powder spray, as compared to the single tube configuration as shown in FIG. 45, in accordance with an embodiment of the of the present invention; and

FIG. 51 is a screen shot of a dual wall drug dispensing system 30, i.e., a double-walled tube configuration, with a 3 mm gap following a lactose powder spray showing little build up or accumulation of lactose powder on inner wall 332 of inner hollow chamber 33a post-powder spray, as compared to the single tube configuration as shown in FIG. 45.

DESCRIPTION OF THE INVENTION

The present disclosure may be understood more readily by reference to the following detailed description and FIGS. of desired embodiments. In the following specification and the claims which follow, reference will be made to a number of terms which shall be defined to have the following meanings.

Although specific terms are used in the following description for the sake of clarity, these terms are intended to refer only to the particular structure of the embodiments selected for illustration in the drawings and are not intended to define or limit the scope of the disclosure. In the drawings and the following description below, it is to be understood that like numeric designations refer to components of like function.

The singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise.

The term “comprising,” as used herein and in a claim, means that the named elements or steps are essential, but other elements or steps may be added, present, comprehended or included. Thus, the term “comprising”, as used herein and in a claim, is synonymous with “including,” “comprehending,” “containing,” or “characterized by,” and therefore is an inclusive or open-ended claim and does not exclude additional, unrecited elements or steps. The term “comprising” should be construed to include the term “consisting of”, which allows the presence of only the named components/steps.

The term “consisting essentially of,” as used herein and in a claim herein, necessarily includes the recited elements or steps, but is open to unlisted elements or steps that do not materially affect the basic and material properties of the subject matter claimed, regardless of whether the subject matter is, e.g., a composition, compound, formulation, process or method.

The term “consists of,” as used herein and in a claim, excludes any element or step not expressly recited and thus is a closed claim.

Numerical values should be understood to include numerical values which are the same when reduced to the same number of significant figures and numerical values which differ from the stated value by less than the experimental error of conventional measurement technique of the type described in the present application to determine the value.

All ranges disclosed herein are inclusive of the recited endpoint and independently combinable (for example, the range of “from 2 mg to 10 mg” is inclusive of the endpoints, 2 mg and 10 mg, and all the intermediate values). The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value; they are sufficiently imprecise to include values approximating these ranges and/or values.

The modifier “about” used in connection with a quantity is inclusive of the stated value and has the meaning dictated by the context. When used in the context of a range, the modifier “about” should also be considered as disclosing the range defined by the absolute values of the two endpoints. For example, the range of “from about 2 to about 10” also discloses the range “from 2 to 10.” The term “about” may refer to plus or minus up to 10% of the indicated number in the applicable or appropriate context. For example, “about 10%” may indicate a range of 9% to 11%, and “about 1” may mean from 0.9-1.1.

As used herein, a “composition” can be a single drug or combination drug (fixed-dose combination) combining at least the two agents, discussed infra, in a single dose. In another embodiment, the “composition” can include a combination of drugs or agents that are each administered or formulated separately or simultaneously. Similarly, a treatment can include administering to a patient a composition as a fixed-dose drug or agent combination, or it can include administering to a patient two or more separate agents or drugs for example, together, substantially together, concomitantly or in a predetermined sequence, frequency and time at their respective dosage strengths or amounts.

Actual dosage levels of a selective drug substance can be varied in order to achieve the effective and safe therapeutic response for a particular patient. The phrase “therapeutically effective amount” or “effective amount” means a sufficient amount of the drug substance to treat injury, diseases or disorders, at a reasonable benefit/risk ratio applicable to any medical treatment. It will be understood, however, that the total daily usage of the drug substances of the present disclosure will be decided by the attending physician or other care provider within the scope of sound medical judgment. If desired, the effective daily dose can be divided into multiple doses for purposes of administration; consequently, single dose drug substances may contain such amounts or submultiples thereof to make up the daily dose. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors, including the injury, disease or disorder being treated and the severity of the injury, disease or disorder; medical history of the patient, age, body weight, general health, sex and diet of the patient, the time of administration, route of administration, the duration of the treatment, other drugs being taken by the patient, and the like. A single administration may usually be sufficient to produce a therapeutic effect, but it is contemplated that multiple administrations will be used over a substantial period of time to assure a continued sustained response.

Accordingly, the present invention provides a single-directional insufflator or breath-powered nasal device 10 for delivering a drug substance, in powder or liquid form, to the nasal airway of a subject, comprising: a closure unit for causing the closure of the oropharyngeal velum of the subject; and a dual wall drug system 30 that provides dual airflow for delivering a vertical, somewhat tightly and narrow or confined, concentrated plume of air flow entraining a drug substance to one of the nostrils of the subject at a driving pressure which would be breath powered to drive the confined and concentrated plume deep within the nasal cavity for targeting the olfactory region, including the olfactory nerve, and the trigeminal nerve mucosa for direct diffusion into the brain and for effective treatment of nasal and/or CNS injury, disease or disorder, in particular TBI, especially concussion, within minutes of nasal application, wherein a single-directional insufflator or breath-powered nasal device 10 of the present invention comprises a nose guard 20 which includes an outlet through which the breath powered air flow is delivered to the one nostril for providing a fluid tight seal between the nose guard 20 and the one nostril.

More specifically, single-directional insufflator or breath-powered nasal device 10 of the present invention comprises a nose guard 20, a one-way valve mouth piece 100, corrugated tubing 80 and means for propelling a dual airflow, e.g., dual wall drug dispensing system 30, i.e., a double-walled tube configuration, for propelling a first airflow carrying the powdered drug substance and propelling a second airflow for surrounding the first airflow for propelling highly concentrated powdered drug substance deep within the nasal cavity, as shown, for example, in FIGS. 1 and 2.

More specifically speaking, the single-directional insufflator or breath-powered nasal device 10 of the present invention is comprised of nose guard 20, dual wall drug dispensing system 30, i.e., a double-walled tube configuration, mesh disc 40, first tube connector 60, corrugated tubing 80, second tube connector 70, and a one-way valve mouth piece 100, as shown in FIGS. 1-2 and 7-10.

The nose guard 20 is tapered and configured with a through-hole 24 and an internal collar 26 against which the top portion 31 of the dual wall drug dispensing system 30 rest when the dual wall drug dispensing system 30, i.e., a double-walled tube configuration, is fully inserted into aperture 24 of nose guard 20, as shown in FIGS. 9-10 and 23-24. Nose guard 20 can be manufactured out of any material that is suitable for nose guard's 20 intended purposes. Seal cap 150, i.e., top cover, as shown in FIGS. 1, 9-10, 13-14 and 26-28, may be inserted into the top 25 of aperture 24 to seal nose guard 20.

The dual wall drug dispensing system 30, is a novel and unique system for delivering one or more drug substances into the nasal cavity and an important aspect of the present invention. The dual wall drug dispensing system 30, i.e., a double-walled tube configuration, is preferably extruded and comprises a top end portion 31 and the bottom end portion 32 and two hollow chambers 33, an inner hollow chamber 33a and an outer hollow chamber 33b. The hollow inner chamber 33a holds drug substance 200 (not shown). The hollow outer chamber 33b, which surrounds the hollow inner chamber 33a, is divided into two, three, four or more separate chambers 34 by rib walls 35. Preferably, hollow outer chamber 33b is divided into three separate chambers 34. See, for example, FIGS. 30-32.

Bridge connector 110 connects one-way valve mouth piece side 131 comprising the one-way valve mouth piece 100 and second tube connector 70 to nose guard side 130 comprising the nose guard 20, dual wall drug dispensing system 30, i.e., a double-walled tube configuration, mesh disc 40, first tube connector 60 and corrugated tubing 80 to maintain the breath-powered insufflator or breath-powered nasal device 10 of the present invention in a constant “U-shape” configuration 140. Bridge connector 120 comprises a bridge 121 sandwiched between two hollow rings 122 and 123, respectively, for sliding over first hollow cuff 81 and second hollow cuff 82, respectively of convoluted middle section with corrugations 80, as shown in FIGS. 1-4 and 7-12, 16-17-19, 21-22, 24-26 and 28.

Alternatively, the bridge connector 120 may be designed with a perforation or score line 124 or any other configuration that allows bridge connector 120 to be broken in two pieces in the event sides 130 and 131 of the device need to be straightened for use by a second person who is assisting, e.g., a concussed person who cannot self-administer the necessary blow force to provide sufficient airflow to effectively propel the drug substance from the single-directional insufflator or breath-powered nasal device 10 of the present invention to effectively treat the concussion with the drug substance. See FIGS. 13 and 14.

The dual wall drug dispensing system 30, i.e., a double-walled tube configuration, is a novel and unique system for delivering one or more drug substances into the nasal cavity and an important aspect of the present invention. The dual wall drug dispensing system 30, i.e., a double-walled tube configuration, comprises a top end portion 31 and the bottom end portion 32 and two hollow chambers 33, an inner hollow chamber 33a and an outer hollow chamber 33b. The hollow inner chamber 33a holds drug substance 200. The hollow outer chamber 33b, which surrounds the hollow inner chamber 33a, is divided into two, three, four or more separate chambers 34 by rib walls 35. Preferably, hollow outer chamber 33b is divided into three separate chambers 34. See, for example, FIGS. 29-32.

First and second tube connectors 60 and 70 are each provided with first top hollow collar 65 and second top hollow collar 75, respectively, for insertion into first hollow cuff 81 and second hollow cuff 82, respectively, of corrugated tubing 80. However, before first top hollow collar 65 and second top hollow collar 75 are inserted into respective first hollow cuff 81 and second hollow cuff 82 of corrugated tubbing 80, bridge connector 110 the first hollow ring 122 and second hollow ring 123 of bridge connector 110 is slid over first hollow cuff 81 and second hollow cuff 82, respectively, to create a u-shape configuration 140. See FIGS. 16-17.

As described herein before, to load the drug substance 200, when in a powdered format, especially a spray-dried format, into the novel single-directional insufflator or breath-powered nasal device 10 of the present invention, a sterilized funnel (not shown) is used to load the powdered drug substance 200 specifically within the inner hollow chamber 33a of the dual wall drug dispensing system 30, i.e., a double-walled tube configuration. The mesh disc 40, which is positioned at bottom end portion 32 of the inner hollow chamber 33a, at the top 66 of the first tube connector 60, is what the loaded powdered drug substance 200 first encounters and against which it rest once fully loaded. Because the pore size of the mesh disc 40 is smaller than the particle size of the powdered drug substance, the powdered drug substance cannot fall through the mesh disc 40. The pores throughout the mesh disc 40, however, permit the blown airflow to penetrate up and through the mesh disc 40 to carry and propel the powdered drug substance 200 from the inner hollow chamber 33a out of nose guard 20 and into the nasal cavity.

Mesh disc 40, as shown for example in FIG. 1, can be manufactured from a multitude of different material options. For example, mesh disc 40 can be manufactured with a PET material. Different materials and mesh size could be used for different applications. By way of example, it may be possible to use liquid with use of a PTFE hydrophobic membrane to contain the dose (depending on chemistry of course). One example of a material contemplated by the present invention for mesh disc 40 is SEFAR MEDIFAB 07-135/40 158 cm, Item Number: 3A07-0135-158-00. One example of a sized mesh disc 40 manufactured with the SEFAR MEDIFAB 07-135/40 158 cm, Item Number: 3A07-0135-158-00 material, that is contemplated for use in accordance with the present, is a mesh disc 40 having a diameter of about 0.411, a thickness of from about 0.004 inches to about 0.012 inches or more, and a surface roughness of about 125 μin.

Preferably, the particle size distribution of the powdered, spray-dried, drug substance 200 is principally in the range of about 1 μm to about 10 μm. In one embodiment, the powdered, spray-dried, drug substance contains a medicament, particularly for the treatment of a nasal condition. Notwithstanding the preferred particle size, the present invention contemplates particle size distribution of a powdered, spray-dried, drug substance to include larger particles, or a smaller fraction of larger particles, typically in the range of about 10 μm to about 30 μm, and preferably in the range of about 20 μm to about 30 μm.

By nesting the inner hollow chamber 33a with powdered, spray-dried, drug substance 200 (not shown) inside the unobstructed larger outer hollow chamber 33b, as shown FIGS. 1-2, 7- and 30, dual wall drug dispensing system 30, i.e., a double walled-tubing configuration, will allow for unmedicated airflow to engage the sidewall of the nasal cavity while allowing the airflow carrying the powdered, spray-dried, drug substance 200, which flows in the center of the unmedicated airflow, to reach its targeted destination deep inside the nasal cavity with minimal drug substance 200 loss.

This benefit is illustrated in FIGS. 48-51, where there is little dry powder build up on the inner walls 332 of inner hollow chambers 33a of dual wall drug dispensing systems 30, i.e., a double walled-tubing configuration, post-powder spray through inner hollow chambers 33a, as compared to the significant dry powder build up on the inner walls of single tube constructions with 3 mm or 4 mm baseline, FIG. 46, and the significant dry powder build up on the inner wall of single tube construction with mm baseline, FIG. 47, and making both tubes almost opaque, post-powder spray through the single tube construction. In contrast, and as shown in FIGS. 48-51, the inner walls 332 of inner hollow chambers 33a of dual wall drug dispensing systems 30, i.e., a double walled-tubing configuration, with 1 mm gap, 1.5 mm gap, 2 mm gap and 3 mm gap, respectively, have a light dusting, with very little powder build up, post-powder spray through inner hollow chamber 33a indicating that more dry powder reaches the targeted destination.

One-way valve mouth piece 100, as shown in FIGS. 1-2, 9-10 and 28, comprises there through conduit 101 with top section 102 and bottom section 103, respectively. Within bottom section 103 sits a one-way valve (not shown) for directing blown air into corrugated tube 80 and preventing reverse airflow. One-way valve mouth piece 100 is designed for insertion into second collar 75 of second tube connector 70 against which bottom section 103 sits when one-way valve mouth piece 100 is fully press-fit into second collar 75 of second tube connector 70. An example of a one-way valve mouth piece 100 contemplated by the present invention is Crosstex Safe-Flo™ Adapter, M1020ADAP one-way valve mouth piece manufactured by Crosstex International. The Safe-Flo™ Adapter is designed with a unique, built-in one-way valve to provide a physical barrier that prevents backflow.

Corrugated tubing 80 is arched to a degree that allows nose guard side 130 and 131 to form a U-shaped configuration 140, as shown in FIGS. 1-2, 7-8, 13, 11, 13 and 37. Corrugated middle section 85 of corrugated tubing 80 has first and second top ends 811 and 821 for respectively receiving first bottom hollow neck 66 of first tube connector 60 and second bottom hollow neck 76 of second tube connector 70 to further the assembly of the single-directional insufflator or breath-powered nasal device 10 of the present invention, as shown in FIGS. 15 and 18.

FIG. 1 is a front assembled elevational angled front view 135 of a single-directional insufflator or breath-powered nasal device 10.

FIG. 2 is a rear assembled elevational angled back view 136 of a single-directional insufflator or breath-powered nasal device 10.

FIG. 3 is a top view 850 of a corrugated tube 80 showing corrugated middle section 85 and bridge connector 110.

FIG. 4 is a bottom view 860 of a corrugated tube 80 showing corrugated middle section 85.

FIG. 5 is an assembled elevational view of nose guard side 130 of the single-directional insufflator or breath-powered nasal device 10.

FIG. 6 is an assembled elevational view of the one-way valve mouth piece side 131 of the single-directional insufflator or breath-powered nasal device 10.

FIG. 7 is a right mouth piece assembled elevational view of a single-directional insufflator or breath-powered nasal device 10.

FIG. 8 is a left mouth piece assembled elevational view of a single-directional insufflator or breath-powered nasal device 10.

FIG. 9 is a right mouth piece front unassembled view of a single-directional insufflator or breath-powered nasal device 10.

FIG. 10 is a left mouth piece front unassembled view of a single-directional insufflator or breath-powered nasal device 10.

FIG. 11 illustrates single-directional insufflator or breath-powered nasal device 10, as shown in FIGS. 1-2 and 4-8, inserted into a nasal cavity of a subject for operation.

FIG. 12 illustrates nose guard 20 of a single-directional insufflator or breath-powered nasal device 10, as shown in FIGS. 13 and 14, that is inserted into a nasal cavity of a first subject to be treated with a drug substance 200 (not shown) and one-way valve mouth piece 100, as shown in FIGS. 13 and 14, inserted between the lips of a second subject for operation of the alternative embodiment by the second subject as shown in FIGS. 13 and 14.

FIG. 13 is a front, right mouth piece, assembled elevational angled view of a single-directional insufflator or breath-powered nasal device 10, wherein the bridge connector 110 is designed with a perforated or score line 142 for breaking bridge connector 110 in two.

FIG. 14 is a front, right mouth piece, assembled elevational angled view of a single-directional insufflator or breath-powered nasal device 10, wherein the bridge connector 110 is broken in two pieces at the perforated or score line 142 for breaking bridge connector 110 into two separate pieces, as shown in FIG. 13.

FIG. 15 illustrates assembling bridge connector 110 to corrugated tubing 80.

FIG. 16 illustrates a perspective view of bridge connector 110 and corrugated tubing 80 in an assembled configuration.

FIG. 17 illustrates a front view of bridge connector 110 and corrugated tubing 80 in an assembled configuration.

FIG. 18 illustrates assembling first tube connector 60 and second tube connector 70 to corrugated tubing 80 assembled with bridge connector 110, as shown in FIGS. 16 and 17.

FIG. 19 illustrates a perspective view of first tube connector 60 and second tube connector 70 assembled with corrugated tubing 80 assembled with bridge connector 110, as shown in FIGS. 16 and 17.

FIG. 20 illustrates a cross-sectional view of tube connectors 60 and 70.

FIG. 21 illustrates inserting a mesh disc 40 into first tube connector 60, wherein first tube connector 60 and second tube connector 70 are assembled with corrugated tubing 80 assembled with bridge connector 110, as shown in FIGS. 16 and 17.

FIG. 22 illustrates inserting a dual wall drug dispensing system 30, i.e., a double-walled tube configuration, into first tube connector 60, wherein mesh disc 40 is inserted into first tube connector 60 and first tube connector 60 and second tube connector 70 are assembled with corrugated tubing 80 assembled with bridge connector 110, as shown in FIGS. 16, 17, 19 and 21.

FIG. 23 illustrates an exploded cross-sectional view of assembled first tube connector 60, wherein mesh disc 40 and dual wall drug dispensing system 30, i.e., a double-walled tube configuration, are assembled within first tube connector 60 and mesh disc 40 is sitting on first seat 61 of first tube connector 60 and first top hollow collar 65 of first tube connector 60 is press-fit into first hollow cuff 81 of corrugated tubing 80.

FIG. 24 illustrates inserting top end portion 31 of dual wall drug dispensing system 30, i.e., the double walled-tube configuration, into bottom 26 of through-hole 24 of nose guard 20, wherein mesh disc 40 is assembled within first tube connector 60 and first tube connector 60 and second tube connector 70 are assembled with corrugated tubing 80 assembled with bridge connector 110, as shown in FIGS. 16, 17, 19, 21 and 22.

FIG. 25 illustrates a front view of assembled nose guard 20, first tube connector 60, mesh disc 40 (not shown), dual wall drug dispensing system 30, i.e., a double-walled tube configuration, first tube connector 60 and second tube connector 70, bride connector 110 and corrugated tubing 80.

FIG. 26 illustrates placing seal cap 150 with seal cap plug 151 into top 25 (not shown) of through-hole 24 (not shown) over nose guard 20 of assembled nose guard 20, first tube connector 60, mesh disc 40 (not shown), dual wall drug dispensing system 30, i.e., a double-walled tube configuration, first tube connector 60 and second tube connector 70, bride connector 110 and corrugated tubing 80.

FIG. 27 illustrates an exploded cross-sectional view of nose guard 20, wherein dual wall drug dispensing system 30, i.e., the double walled-tube, is inserted through through-hole 24 of nose guard 20, top end portion 31 of dual wall drug dispensing system 30, i.e., a double-walled tube configuration, is seated against nose guard seat 22 of nose guard 20 and seal cap 150 is positioned over nose guard 20 with nose guard stem 151 is inserted through top 25 and into through-hole 24 of nose guard 20.

FIG. 28 illustrates inserting bottom section 102 of one-way valve mouth piece 100 into of dual wall drug dispensing system 30, i.e., the double walled-tube, into second top hollow collar 75 of second tube connector 70, assembled seal cap 150, nose guard 20, first tube connector 60, mesh disc 40 (not shown), dual wall drug dispensing system 30, i.e., a double-walled tube configuration, first tube connector 60 and second tube connector 70, bride connector 110 and corrugated tubing 80.

FIG. 29 is an exploded cross-sectional view of inner hollow chamber 33a, having outer wall 331 and inner wall 332, and outer hollow chamber 33b having outer wall 333 and inner wall 334 of dual wall drug dispensing system 30, i.e., a double-walled tube configuration, illustrating one size tube diameters, wherein, outer hollow chamber 33b having outer wall 333 diameter of 11 mm and inner wall 334 diameter of 9 mm and inner hollow chamber 33a having outer wall 331 diameter of 6 mm and inner wall 332 diameter of 4 mm with internal gap 36 of 1.5 mm and an inner hollow chamber 33a having an internal diameter of 4 mm. Illustrations of alternative size tube diameters are: (a) outer hollow chamber 33b having outer wall 333 diameter of 10 mm and inner wall 334 diameter of 8 mm and inner hollow chamber 33a having outer wall 331 diameter of 6 mm and inner wall 332 diameter of 4 mm with internal gap 36 of 1 mm and an inner hollow chamber 33a having an internal diameter of 4 mm; (b) outer hollow chamber 33b having outer wall 333 diameter of 11 mm and inner wall 334 diameter of 9 mm and inner hollow chamber 33a having outer wall 331 diameter of 5 mm and inner wall 332 diameter of 3 mm with internal gap 36 of 2 mm and an inner hollow chamber 33a having an internal diameter of 3 mm; and (c) outer hollow chamber 33b having outer wall 333 diameter of 13 mm and inner wall 334 diameter of 11 mm and inner hollow chamber 33a having outer wall 331 diameter of 5 mm and inner wall 332 diameter of 3 mm with an internal gap 36 of 3 mm and an inner hollow chamber 33a having an internal diameter of 3 mm.

FIG. 30 is a view of dual wall drug dispensing system 30, i.e., a double-walled tube configuration, bottom end portion 32, internal gap 36 and the two hollow chambers 33, i.e., the inner hollow chamber 33a and the outer hollow chamber 33b, wherein the outer hollow chamber 33b is divided into three separate chambers 34 by rib walls 35.

FIG. 31 is a cross-sectional view of dual wall drug dispensing system 30, i.e., a double-walled tube configuration, as shown in FIGS. 9, 10, 19 and 30.

FIG. 32 is a cross-sectional view taken along line A of dual wall drug dispensing system 30, i.e., a double-walled tube configuration, as shown in FIGS. 9, 10, 19, 30 and 31.

FIG. 33 is a cross-sectional view of tube connector 60 or 70 taken along line A, as shown in FIGS. 9, 10, 18, 23 and 31.

FIG. 34 is a cross-sectional view of tube connector 60 or 70, as shown in FIGS. 9, 10, 18, 23 and 31.

FIG. 35 is a cross-sectional view of nose guard 20 taken along line A depicting top 25 of through-hole 24, as shown in FIGS. 9, 10, 24, 25 and 27.

FIG. 36 illustrates an alternative cross-sectional view of nose guard 20, depicting top 25 and bottom 26 of through-hole 24 and nose guard seat 22, as shown in FIGS. 9, 10, 24, 25, 27 and 35.

FIG. 37 illustrates an assembled view of single-directional insufflator or breath-powered nasal device 10 depicting one-way valve mouth piece 100, first air-flow directional band 160, first tube connector 60, corrugated tubing 80, bridge connector 110, second tube connector 70, second air-flow directional band 170, dual wall drug dispensing system 30 and nose guard 20.

FIG. 36 illustrates an alternative one-way valve mouth piece 131 view of and assembled single-directional insufflator or breath-powered nasal device 10 nose guard, as shown in FIG. 6.

FIG. 39 illustrates an unassembled view of seal cap 150, i.e., top plug, nose guard 20, one-way valve dual wall drug dispensing system 30, i.e., a double-walled tube configuration, mesh disc 40, and alternative connector 180 for connecting one-way dual wall drug dispensing system 30, i.e., the double walled-tube, and corrugated tubing 80.

FIG. 40 illustrates an alternative cross-sectional view of seal cap 150, i.e., top plug, nose guard 20, and one-way valve dual wall drug dispensing system 30, i.e., a double-walled tube configuration, assembled with alternative connector 180, as shown in FIG. 39;

FIG. 41 illustrates an assembled front view of nose guard 20, dual wall drug dispensing system 30, i.e., a double-walled tube configuration, alternative connector 180, corrugated tubing 80, and nose guard 20.

FIG. 42 illustrates a top view of a tray packaged with twenty single-directional insufflator or breath-powered nasal fully assembled devices herein, wherein the 20 such devices 10 are positioned in two rows of five pairs of such devices, wherein each such pair shows two such devices positioned in an interlocking position with respect to one another.

FIG. 43 illustrates a side top view of a tray packaged exposing an internal side longitudinal wall with twenty single-directional insufflator or breath-powered nasal fully assembled devices herein, wherein the 20 such devices 10 are positioned in two rows of five pairs of such devices, wherein each such pair shows two such devices positioned in an interlocking position with respect to one another.

FIG. 44 illustrates a screen shot comparing the width of a lactose powder spray between a single tube configuration and a dual wall drug dispensing system 30, i.e., a double-walled tube configuration, of the present invention in which the internal diameter of the inner tube of the double tube is about 4 mm and the gap between the inner and outer tubes of the double tube is either 1.5 mm or 1 mm to a single tube configuration.

FIG. 45 illustrates a screen shot comparing the width of a lactose powder spray between a single tube configuration and a dual wall drug dispensing system 30, i.e., a double-walled tube configuration, of the present invention in which the internal diameter of the inner tube of the double tube is about 3 mm and the gap between the inner and outer tubes of the double tube is either 2 mm or 3 mm to a single tube configuration.

As shown in FIGS. 44 and 45, when comparing the width of the powder spray at the same height, the spray width of dual wall drug dispensing system 30, i.e., a double-walled tube configuration, with internal diameters of 4 mm and 3 mm, respectively, of inner hollow chambers 33a stays more centered that that of a baseline single tubular configuration. In other words, the baseline single tubular configuration spread out wider and sooner than dual wall drug dispensing system 30, i.e., a double-walled tube configuration. These results demonstrate that dual wall drug dispensing system 30, i.e., a double-walled tube configuration, would allow drug substance 200 (not shown) to possibly reach deeper into a nasal cavity, rather than collecting on the walls of the nose. In addition, because it is believed that the 3 mm ID devices 30 may disperse spray powder at lower heights and reach lower maximum heights than the 4 mm ID devices 30 of FIGS. 44-45, dual wall drug dispensing system 30, i.e., a double-walled tube configuration of the present invention that are configured with inner hollow chambers 33a that have internal diameters of about 4 mm ID or greater are preferred.

FIG. 46 illustrates a screen shot of a single tube configuration with a 3 mm baseline following a lactose powder spray showing significant build up or accumulation of lactose powder on internal wall post-powder spray, as compared to the single tube configuration as shown in FIG. 45.

FIG. 47 illustrates a screen shot of a single tube configuration with a 4 mm baseline following a lactose powder spray showing significant build up or accumulation of lactose powder on internal wall post-powder spray, as compared to the single tube configuration as shown in FIG. 45 . . .

FIG. 48 illustrates a screen shot of a dual wall drug dispensing system 30, i.e., a double-walled tube configuration, with a 1 mm gap following a lactose powder spray showing little build up or accumulation of lactose powder on inner wall 332 of inner hollow chamber 33a post-powder spray, as compared to the single tube configuration as shown in