Therapeutic composition for improving symptoms of obstructive sleep apnea

Abstract

A therapeutic composition for improving the symptoms of obstructive sleep apnea, the therapeutic composition comprising an aqueous solution. the aqueous solution may comprise: acetazolamide with a final concentration between 22.5 mg / ml and 52.5 mg / ml; ibuprofen lysine with a final concentration between 4 mg / ml and 20 mg / ml; propylene glycol with a final concentration between 0.5 mg / ml and 7.5 mg / ml; sodium chloride with a final concentration between 6 mg / ml and 9 mg / ml; and a preservative with a final concentration between 0.05 mg / ml and 0.15 mg / ml.

Description

THERAPEUTIC COMPOSITION FOR IMPROVING SYMPTOMS OFOBSTRUCTIVE SLEEP APNEACROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of priority from U.S. Provisional Patent Application Ser. No. 63563468, filed on March. 11, 2024, entitled “THERAPEUTIC COMPOSITION FOR TREATING OBSTRUCTIVE SLEEP APNEA” which is incorporated herein by reference in its entirety.TECHNICAL FIELD

[0002] The present disclosure is generally related to an exemplary therapeutic composition for improving symptoms of obstructive sleep apnea and an exemplary method for preparation thereof, and in particular to an exemplary therapeutic composition comprising acetazolamide and ibuprofen.BACKGROUND

[0003] The common condition known as obstructive sleep apnea (OSA) is characterized by the patient's pharyngeal airway repeatedly closing while they are asleep. Affected individuals usually breathe extremely well when they are awake, but they have difficulty maintaining an open airway when they are asleep. The collapse usually occurs behind the tongue, soft palate, or uvula, or a combination of these. Though this isn't always the case, awakening from sleep usually occurs at the same time as airway opening. These respiratory stops are usually followed by the onset of potentially fatal hypoxia and hypercapnia. This means that during the night, the individual alternates between apnea and hyperpnea, as well as the related intermittent hypoxia and hypercapnia, and between alertness and sleep. Symptoms of sleep apnea include excessive snoring, fatigue during the day, and being seengasping, choking, or experiencing an apneic fit. They might also experience morning headaches, sexual dysfunction, and depression. Patients who present with these complaints are then referred to a sleep laboratory for an overnight study, wherein breathing effort, oxygen saturation, sleep, electrocardiogram (ECG), and leg electromyogram (EMG) are monitored.

[0004] The terms "apnea" and "hypopnea" refer to the two types of aberrant respiratory episodes; a hypopnea is similar to an apnea but does not result in a complete cessation of breathing for 10 seconds or longer. Generally speaking, a hypopnea is only recorded if it is accompanied by a 3% to 4% decrease in arterial oxygen saturation or an awakening from sleep. The term "apnea hypopnea index" (AHI) counts the number of apneas and hypopneas that occur during each hour of sleep; an AHI of 5 or more is considered abnormal. Daytime symptoms and an AHI greater than 5 are required for the diagnosis of OSA syndrome. AHI values of 5 to 15 are considered mild, 15 to 30 are considered moderate, and 30 or above are considered severe. In the absence of symptoms, 24% of men and 9% of women have an AHI above 5.

[0005] The two main categories of clinical consequences associated with OSA are neurocognitive and cardiovascular. The preponderance of data suggests that intermittent hypoxia is the cause of the detrimental effects on the cardiovascular system; however, the disruption of sleep induced by sleep apnea is believed to be the origin of the neurocognitive problems. However, the conclusions have not been sufficiently supported. Adverse neurocognitive consequences encompass fatigue during the day, reduced focus, an increase in workplace and auto accidents, and a general deterioration in life satisfaction. Apnea therapy can greatly alleviate most of these difficulties, while not all of them will become normal. Thus, there is a need to develop a formulation that contain effective therapeutic agents, with high efficacy to use in patients who suffer from obstructive sleep apnea.SUMMARY

[0006] This summary is intended to provide an overview of the subject matter of the present disclosure, and is not intended to identify essential elements or key elements of the subject matter, nor is it intended to be used to determine the scope of the claimed implementations. Its sole purpose is to present some concepts of one or more exemplary aspects in a simplified form as a prelude to the more detailed description that is presented later. The proper scope of the present disclosure may be ascertained from the claims set forth below in view of the detailed description below and the drawings.

[0007] One or more exemplary embodiments describe an exemplary therapeutic composition for improving the symptoms of obstructive sleep apnea. In an exemplary embodiment, an exemplary therapeutic composition may comprise an exemplary aqueous solution. In an exemplary embodiment, an exemplary aqueous solution may comprise: acetazolamide with a final concentration between 22.5 mg / ml and 52.5 mg / ml; ibuprofen lysine with a final concentration between 4 mg / ml and 20 mg / ml; propylene glycol with a final concentration between 0.5 mg / ml and 7.5 mg / ml; sodium chloride with a final concentration between 6 mg / ml and 9 mg / ml; and an exemplary preservative with a final concentration between 0.05 mg / ml and 0.15 mg / ml. In an exemplary embodiment, an exemplary preservative may be selected from the group consisting of benzalkonium chloride, propyl paraben, methyl paraben, chlorobutanol, and a combination thereof. In an exemplary embodiment, an exemplary preservative may comprise benzalkonium chloride with a concentration between 0.08 mg / ml and 0.1 mg / ml.

[0008] In an exemplary embodiment, an exemplary therapeutic composition may be formulated as an exemplary nasal drop. In an exemplary embodiment, an exemplary nasal drop may be applied between one drop and 4 drops every 24 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal drop may beapplied between one drop and 4 drops every 12 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal drop may be applied between one drop and 4 drops every 8 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal drop may be applied between one drop and 4 drops every 6 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal drop may be applied between one drop and 4 drops every 4 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary therapeutic composition may be formulated as an exemplary nasal spray. In an exemplary embodiment, an exemplary nasal spray may be applied between one puff and 4 puffs every 24 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal spray may be applied between one puff and 4 puffs every 12 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal spray may be applied between one puff and 4 puffs every 8 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal spray may be applied between one puff and 4 puffs every 6 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal spray may be applied between one puff and 4 puffs every 4 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary therapeutic composition may be formulated as an exemplary inhaler spray. In an exemplary embodiment, an exemplary inhaler spray may be applied between one puff and 4 puffs every 24 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary inhaler spray may be applied between one puff and 4 puffs every 12 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary inhaler spray may be applied between one puff and 4 puffs every 8 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary inhaler spray may be applied between one puff and 4 puffs every6 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary inhaler spray may be applied between one puff and 4 puffs every 4 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary therapeutic composition may be formulated as an exemplary oral drop. In an exemplary embodiment, an exemplary oral drop may be applied between one drop and 4 drops every 24 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary oral drop may be applied between one drop and 4 drops every 12 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary oral drop may be applied between one drop and 4 drops every 8 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary oral drop may be applied between one drop and 4 drops every 6 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary oral drop may be applied between one drop and 4 drops every 4 hours a day in a patient with obstructive sleep apnea.

[0009] One or more exemplary embodiments describe an exemplary method of producing an exemplary therapeutic composition for improving the symptoms of obstructive sleep apnea. In an exemplary embodiment, an exemplary method may comprise: forming an exemplary first solution comprising acetazolamide and sodium hydroxide with a concentration between 420 mg / ml and 450 mg / ml; forming an exemplary second solution comprising ibuprofen lysine with a concentration between 90 mg / ml and 110 mg / ml, and sodium chloride with a concentration between 6 mg / ml and 9 mg / ml; forming an exemplary third solution comprising acetazolamide, ibuprofen lysine, sodium hydroxide, and sodium chloride; adjusting a pH level of an exemplary third solution between 7 and 9.5; forming an exemplary diluted third solution comprising acetazolamide with a concentration between 22.5 mg / ml and 52.5 mg / ml, ibuprofen lysine with a concentration between 4 mg / ml and 20 mg / ml, and sodium chloride with a concentration between 6 mg / ml and 9 mg / ml; forming anexemplary final solution comprising acetazolamide with a final concentration between 22.5 mg / ml and 52.5 mg / ml; ibuprofen lysine with a final concentration between 4 mg / ml and 20 mg / ml; propylene glycol with a final concentration between 0.5 mg / ml and 7.5 mg / ml; sodium chloride with a final concentration between 6 mg / ml and 9 mg / ml; and an exemplary preservative comprising benzalkonium chloride with a final concentration between 0.08 mg / ml and 0.1 mg / ml; and filtering an exemplary final solution comprising acetazolamide, ibuprofen lysine, sodium chloride, propylene glycol and an exemplary preservative by passing an exemplary final solution through an exemplary syringe filter with a particle size removal between 0.42 micro-meters and 0.45 micro-meters.

[0010] In an exemplary embodiment, forming an exemplary third solution may comprise mixing an exemplary first solution and an exemplary second solution with a volume ratio of 1:3 (an exemplary second solution: an exemplary first solution) while stirring with a speed range between 200 round per minute (rpm) and 300 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 8 minutes and 15 minutes. In an exemplary embodiment, forming an exemplary diluted third solution may comprise adding water to an exemplary third solution while stirring with a speed range between 60 rpm and 80 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 1 minutes and 10 minutes. In an exemplary embodiment, forming an exemplary final solution may comprise adding an exemplary preservative comprising benzalkonium chloride with a concentration between 0.08 mg / ml and 0.1 mg / ml (with respect to the final concentration of an exemplary final solution) and propylene-glycol with a concentration between 0.5 mg / ml and 7.5 mg / ml (with respect to the final concentration of an exemplary final solution) to an exemplary diluted third solution.

[0011] In an exemplary embodiment, forming an exemplary first solution may comprise: forming an exemplary solution of acetazolamide with a concentration between 180 mg / mland 190 mg / ml by dissolving an exemplary powder of acetazolamide in water; forming an exemplary fourth solution comprising acetazolamide with a concentration between 930 mg / ml and 950 mg / ml, and sodium hydroxide with a concentration between 540 mg / ml and 560 mg / ml by mixing an exemplary solution of acetazolamide and an exemplary solution of sodium hydroxide (with a concentration of about 8 mg / ml) with a volumetric ratio of 1 : 1 (an exemplary solution of acetazolamide: an exemplary solution of sodium hydroxide) while stirring with a speed range between 60 rpm and 80 rpm, at a temperature between 25 °C and 30 °C, and for a time duration between 1 minutes and 5 minutes; forming an exemplary porous powder comprising acetazolamide and sodium hydroxide by freeze-drying an exemplary fourth solution at a temperature level between 48 °C and 52 °C, and for a time duration between 50 minutes and 70 minutes; forming an exemplary first mixture comprising an exemplary porous powder with a concentration between 14.9 mg / ml and 29.8 mg / ml by dissolving an exemplary porous powder in water while stirring with a speed range between 60 rpm and 80 rpm, at a temperature between 25 °C and 30 °C, and for a time duration between 1 minutes and 2 minutes; adjusting a pH level of an exemplary first mixture between 7 and 8; and forming an exemplary diluted first mixture comprising acetazolamide with a concentration between 70 mg / ml and 80 mg / ml and sodium hydroxide with a concentration between 420 mg / ml and 450 mg / ml by adding water to an exemplary first mixture.

[0012] In an exemplary embodiment, forming an exemplary second solution comprising forming an exemplary solution of sodium chloride with a concentration between 6 gr / ml and 9 mg / ml by dissolving sodium chloride with a concentration between 6 mg / ml and 9 mg / ml in water while stirring with a speed range between 200 rpm and 300 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 8 minutes and 15 minutes; forming an exemplary fifth solution comprising sodium chloride with a concentration between 6 mg / ml and 9 mg / ml and ibuprofen lysine with a concentration between 90-110 mg / ml byadding ibuprofen lysine to an exemplary solution of sodium chloride while stirring with a speed range between 200 rpm and 300 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 8 minutes and 12 minutes; adjusting a pH level of an exemplary fifth solution between 7.2 and 7.6; forming an exemplary diluted fifth solution comprising ibuprofen lysine with a concentration between 90 mg / ml and 110 mg / ml, and sodium chloride with a concentration between 6 mg / ml and 9 mg / ml by adding water to an exemplary fifth solution while stirring with a speed range between 200 rpm and 300 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 8 minutes and 15 minutes; and filtering an exemplary diluted fifth solution by passing an exemplary diluted fifth solution through an exemplary syringe filter with a particle size removal between 0.21 micro-meters and 0.23 micro-meters.

[0013] This Summary may introduce a number of concepts in a simplified format; the concepts are further disclosed within the “Detailed Description” section. This Summary is not intended to configure essential / key features of the claimed subject matter, nor is intended to limit the scope of the claimed subject matter.BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The novel features which are believed to be characteristic of the present disclosure, as to its structure, organization, use and method of operation, together with further objectives and advantages thereof, will be better understood from the following drawings in which an exemplary embodiment will now be illustrated by way of example. It is expressly understood, however, that the drawings are for the purpose of illustration and description only and are not intended as a definition of the limits of one or more exemplary embodiments. One or more exemplary embodiments will now be described by way of example in association with the accompanying drawings in which:

[0015] FIG. 1 illustrates flowchart of exemplary method for producing an exemplary therapeutic composition for improving the symptoms of obstructive sleep apnea, consistent with one or more exemplary embodiments of the present disclosure;

[0016] FIG. 2 illustrates an exemplary method of step for forming an exemplary first solution comprising acetazolamide and sodium hydroxide, consistent with one or more exemplary embodiments of the present disclosure; and

[0017] FIG. 3 illustrates an exemplary method of step for forming an exemplary second solution comprising ibuprofen lysine and sodium chloride, consistent with one or more exemplary embodiments of the present disclosure.DETAILED DESCRIPTION

[0018] In the following detailed description, numerous specific details are set forth by way of examples to provide a thorough understanding of the relevant teachings related to exemplary embodiments. However, it should be apparent that the present teachings may be practiced without such details. In other instances, well known methods, procedures, components, and / or circuitry have been described at a relatively high-level, without detail, in order to avoid unnecessarily obscuring aspects of the present teachings.

[0019] The following detailed description is presented to enable a person skilled in the art to make and use the methods and devices disclosed in one or more exemplary embodiments. For purposes of explanation, specific nomenclature is set forth to provide a thorough understanding of one or more exemplary embodiments. However, it will be apparent to one skilled in the art that these specific details are not required to practice the disclosed exemplary embodiments. Descriptions of specific exemplary embodiments are provided only as representative examples. Various modifications to exemplary implementations will be plain to one skilled in the art, and the general principles defined herein may be applied to other implementations and applications without departing from thescope of one or more exemplary embodiments. The present disclosure is not intended to be limited to the implementations shown, but is to be accorded the widest possible scope consistent with the principles and features disclosed herein.

[0020] Disclosed here is an exemplary therapeutic composition which may be used to reduce and improve the symptoms of obstructive sleep apnea. In an exemplary embodiment, an exemplary therapeutic composition may comprise an exemplary aqueous solution. In an exemplary embodiment, an exemplary aqueous solution may comprise an exemplary antiinflammatory agent, an exemplary diuretic agent, sodium hydroxide, sodium chloride, propylene glycol, and an exemplary preservative component. In an exemplary embodiment, an exemplary anti-inflammatory agent may be selected from the group consisting of an exemplary non-steroidal anti-inflammatory drug, an exemplary steroidal anti-inflammatory drug (corticosteroids), and a combination thereof. In an exemplary embodiment, an exemplary non-steroidal anti-inflammatory drug may be selected from the group consisting of indomethacin, ketorolac, naproxen, ibuprofen lysine, ibuprofen, meloxicam, baclofen, mefenamic acid, celecoxib, and a combination thereof. In an exemplary embodiment, an exemplary steroidal anti-inflammatory drug (corticosteroids) may be selected from the group consisting of triamcinolone, methylprednisolone, budesonide, dexamethasone, prednisolone, hydrocortisone, betamethasone, fluticasone, beclomethasone, mometasone, and a combination thereof. In an exemplary embodiment, an exemplary diuretic agent may be selected from the group consisting of acetazolamide, dorzolamide, and a combination thereof. In an exemplary embodiment, an exemplary preservative may be selected from the group consisting of benzalkonium chloride, propyl paraben, methyl paraben, chlorobutanol, and a combination thereof.

[0021] In an exemplary embodiment, an exemplary aqueous solution may comprise acetazolamide, ibuprofen lysine, sodium hydroxide, sodium chloride, propylene glycol andan exemplary preservative. In an exemplary embodiment, an exemplary aqueous solution may comprise acetazolamide with a final concentration between 22.5 mg / ml and 52.5 mg / ml; ibuprofen lysine with a final concentration between 4 mg / ml and 20 mg / ml; sodium chloride with a final concentration between 6 mg / ml and 9 mg / ml; propylene glycol with a final concentration between 0.5 mg / ml and 7.5 mg / ml; and an exemplary preservative with a final concentration between 0.08 mg / ml and 0.1 mg / ml.

[0022] In an exemplary embodiment, an exemplary therapeutic composition may be formulated as an exemplary nasal drop. In an exemplary embodiment, an exemplary nasal drop may be applied between one drop and 4 drops every 24 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal drop may be applied between one drop and 4 drops every 12 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal drop may be applied between one drop and 4 drops every 8 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal drop may be applied between one drop and 4 drops every 6 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal drop may be applied between one drop and 4 drops every 4 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary therapeutic composition may be formulated as an exemplary nasal spray. In an exemplary embodiment, an exemplary nasal spray may be applied between one puff and 4 puffs every 24 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal spray may be applied between one puff and 4 puffs every 12 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal spray may be applied between one puff and 4 puffs every 8 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary nasal spray may be applied between one puff and 4 puffs every 6 hours a day in a patient with obstructivesleep apnea. In an exemplary embodiment, an exemplary nasal spray may be applied between one puff and 4 puffs every 4 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary therapeutic composition may be formulated as an exemplary inhaler spray. In an exemplary embodiment, an exemplary inhaler spray may be applied between one puff and 4 puffs every 24 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary inhaler spray may be applied between one puff and 4 puffs every 12 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary inhaler spray may be applied between one puff and 4 puffs every 8 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary inhaler spray may be applied between one puff and 4 puffs every 6 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary inhaler spray may be applied between one puff and 4 puffs every 4 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary therapeutic composition may be formulated as an exemplary oral drop. In an exemplary embodiment, an exemplary oral drop may be applied between one drop and 4 drops every 24 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary oral drop may be applied between one drop and 4 drops every 12 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary oral drop may be applied between one drop and 4 drops every 8 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary oral drop may be applied between one drop and 4 drops every 6 hours a day in a patient with obstructive sleep apnea. In an exemplary embodiment, an exemplary oral drop may be applied between one drop and 4 drops every 4 hours a day in a patient with obstructive sleep apnea.

[0023] One or more exemplary embodiments describe an exemplary method for producing an exemplary therapeutic composition for improving the symptoms of obstructivesleep apnea. Referring to the figures, FIG. 1 illustrates flowchart of exemplary method 100 for producing an exemplary therapeutic composition for improving the symptoms of obstructive sleep apnea, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, exemplary method 100 may comprise: forming an exemplary first solution comprising acetazolamide and sodium hydroxide (step 102); forming an exemplary second solution comprising ibuprofen lysine, and sodium chloride (step 104); forming an exemplary third solution comprising acetazolamide, ibuprofen lysine, sodium hydroxide, and sodium chloride (step 106); adjusting a pH level of an exemplary third solution between 7 and 9.5 (step 108); diluting an exemplary third solution (step 110); forming an exemplary final solution comprising acetazolamide, ibuprofen lysine, sodium chloride, propylene-glycol and an exemplary preservative (step 112); and filtering an exemplary final solution comprising acetazolamide, ibuprofen lysine, sodium chloride, propylene glycol and an exemplary preservative (step 114).

[0024] In an exemplary embodiment, details of step 102 for forming an exemplary first solution comprising acetazolamide and sodium hydroxide are described in context of elements presented in FIG. 2. FIG. 2 illustrates an exemplary method of step 102 for forming an exemplary first solution comprising acetazolamide and sodium hydroxide, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, an exemplary first solution may comprise acetazolamide with a concentration between 70 mg / ml and 80 mg / ml (with respect to the final concentration of an exemplary first solution) and sodium hydroxide with a concentration between 420 mg / ml and 450 mg / ml (with respect to the final concentration of an exemplary first solution). In an exemplary embodiment, an exemplary method of step 102 may comprise: forming an exemplary solution of acetazolamide with a concentration between 180 mg / ml and 190 mg / ml (step 200); forming an exemplary fourth solution comprising acetazolamide and sodium hydroxide (step 202);forming an exemplary porous powder comprising acetazolamide and sodium hydroxide (step204); forming an exemplary first mixture comprising an exemplary porous powder (step 206); adjusting a pH level of an exemplary first mixture between 7 and 8 (step 208); and diluting an exemplary first mixture (step 210).

[0025] In further detail with respect to step 200, step 200 may include forming an exemplary solution of acetazolamide with a concentration between 180 mg / ml and 190 mg / ml. In an exemplary embodiment, forming an exemplary solution of acetazolamide with a concentration between 180 mg / ml and 190 mg / ml may comprise dissolving acetazolamide in water in an exemplary laboratory container including, but not limited to, beakers, tins, flasks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, dissolving acetazolamide in water in an exemplary laboratory container may comprise adding an exemplary powder of acetazolamide (e.g., using spatula) with a concentration between 180 mg / ml and 190 mg / ml (with respect to the final concentration of an exemplary solution of acetazolamide), and water (e.g., using a sampler, graduated cylinder / tube, etc.) to an exemplary laboratory container, such as a beaker, while stirring using a stirrer, e.g., a magnetic stirrer with a speed range between 60 round per minute (rpm) and 80 rpm, at a temperature between 25 °C and 30 °C, and for a time duration between 1 minutes and 2 minutes. In an exemplary embodiment, an exemplary powder of acetazolamide may be weighed by an exemplary laboratory scale. In an exemplary embodiment, an exemplary powder of acetazolamide may have a purity of 99 mg / ml.

[0026] In further detail with respect to step 202, step 202 may include forming an exemplary fourth solution comprising acetazolamide and sodium hydroxide. In an exemplary embodiment, forming an exemplary fourth solution comprising acetazolamide and sodium hydroxide may comprise forming an exemplary fourth solution comprising acetazolamide with a concentration between 930 mg / ml and 950 mg / ml (with respect to the finalconcentration of an exemplary fourth solution), and sodium hydroxide with a concentration between 540 mg / ml and 560 mg / ml (with respect to the final concentration of an exemplary fourth solution). In an exemplary embodiment, forming an exemplary fourth solution comprising acetazolamide with a concentration between 930 mg / ml and 950 mg / ml (with respect to the final concentration of an exemplary fourth solution), and sodium hydroxide with a concentration between 540 mg / ml and 560 mg / ml (with respect to the final concentration of an exemplary fourth solution) may include mixing an exemplary solution of acetazolamide (i.e., an exemplary solution of acetazolamide set forth in step 200) and an exemplary solution of sodium hydroxide (with a concentration of about 8 mg / ml) with a volumetric ratio of 1: 1 (an exemplary solution of acetazolamide: an exemplary solution of sodium hydroxide) in an exemplary laboratory container including, but not limited to, beakers, tins, flasks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, mixing an exemplary solution of acetazolamide (i.e., an exemplary solution of acetazolamide set forth in step 200) and an exemplary solution of sodium hydroxide (with a concentration of about 8 mg / ml) with a volumetric ratio of 1 : 1 (an exemplary solution of acetazolamide: an exemplary solution of sodium hydroxide) in an exemplary laboratory container may include adding an exemplary solution of acetazolamide (e.g., using a sampler, graduated cylinder / tube, etc.) and an exemplary solution of sodium hydroxide e.g., using a sampler, graduated cylinder / tube, etc.) with a volumetric ratio of 1: 1 (an exemplary solution of acetazolamide: an exemplary solution of sodium hydroxide) to an exemplary laboratory container, such as a beaker, while stirring using a stirrer, e.g., a magnetic stirrer with a speed range between 60 rpm and 80 rpm, at a temperature between 25 °C and 30 °C, and for a time duration between 1 minutes and 5 minutes.

[0027] In further detail with respect to step 204, step 204 may include forming an exemplary porous powder comprising acetazolamide and sodium hydroxide. In an exemplaryembodiment, forming an exemplary porous powder comprising acetazolamide and sodium hydroxide may include freeze-drying an exemplary fourth solution comprising acetazolamide, and sodium hydroxide at a temperature level between 48 °C and 52 °C, and for a time duration between 50 minutes and 70 minutes.

[0028] In further detail with respect to step 206, step 206 may include forming an exemplary first mixture comprising an exemplary porous powder. In an exemplary embodiment, forming an exemplary first mixture comprising an exemplary porous powder may comprise forming an exemplary first mixture comprising an exemplary porous powder (i.e., an exemplary porous powder set forth in step 204) with a concentration between 14.9 mg / ml and 29.8 mg / ml. In an exemplary embodiment, forming an exemplary first mixture comprising an exemplary porous powder (i.e., an exemplary porous powder set forth in step 204) with a concentration between 14.9 mg / ml and 29.8 mg / ml may comprise dissolving an exemplary porous powder (i.e., an exemplary porous powder set forth in step 204) in water. In an exemplary embodiment, dissolving an exemplary porous powder (i.e., an exemplary porous powder set forth in step 204) in water may comprise mixing an exemplary porous powder (i.e., an exemplary porous powder set forth in step 204) with a concentration between 14.9 mg / ml and 29.8 mg / ml (with respect to the final concentration of an exemplary first mixture), and water in exemplary laboratory container including, but not limited to, beakers, tins, flasks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, mixing an exemplary porous powder (i.e., an exemplary porous powder set forth in step 204) with a concentration between 14.9 mg / ml and 29.8 mg / ml (with respect to the final concentration of an exemplary first mixture), and water in exemplary laboratory container may include adding an exemplary porous powder (i.e., an exemplary porous powder set forth in step 204) with a concentration between 14.9 mg / ml and 29.8 mg / ml (with respect to the final concentration of an exemplary first mixture) (e.g., usingspatula), and water (e.g., using a sampler, graduated cylinder / tube, etc.) to an exemplary laboratory container, such as a beaker, while stirring using a stirrer, e.g., a magnetic stirrer with a speed range between 60 rpm and 80 rpm, at a temperature between 25 °C and 30 °C, and for a time duration between 1 minutes and 2 minutes.

[0029] In further detail with respect to step 208, step 208 may include adjusting a pH level of an exemplary first mixture between 7 and 8. In an exemplary embodiment, adjusting a pH level of an exemplary first mixture between 7 and 8 may include measuring a pH level of an exemplary first mixture and subsequently adding hydrochloric acid or sodium hydroxide (based on the pH level measurement) to an exemplary first mixture in an exemplary laboratory container, such as a beaker, while stirring using a stirrer, e.g., a magnetic stirrer.

[0030] In further detail with respect to step 210, step 210 may include diluting an exemplary first mixture. In an exemplary embodiment, diluting an exemplary first mixture may include adding water to an exemplary first mixture in an exemplary laboratory container including, but not limited to, beakers, tins, flasks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, adding water to an exemplary first mixture in an exemplary laboratory container may include adding water (e.g., using a sampler, graduated cylinder / tube, etc.) to an exemplary first mixture in an exemplary laboratory container, such as a beaker to form an exemplary first solution comprising acetazolamide with a concentration between 70 mg / ml and 80 mg / ml (with respect to the final concentration of an exemplary first solution) and sodium hydroxide with a concentration between 420 mg / ml and 450 mg / ml (with respect to the final concentration of an exemplary first solution).

[0031] In an exemplary embodiment, details of step 104 for forming an exemplary second solution comprising ibuprofen lysine, and sodium chloride are described in contextof elements presented in FIG. 3. FIG. 3 illustrates an exemplary method of step 104 for forming an exemplary second solution comprising ibuprofen lysine and sodium chloride, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, forming an exemplary second solution comprising ibuprofen lysine and sodium chloride may comprise forming an exemplary second solution comprising ibuprofen lysine with a concentration between 90 mg / ml and 110 mg / ml (with respect to the final concentration of an exemplary second solution), and sodium chloride with a concentration between 6 mg / ml and 9 mg / ml (with respect to the final concentration of an exemplary second solution). In an exemplary embodiment, an exemplary method of step 104 may comprise: forming an exemplary solution of sodium chloride (step 300); forming an exemplary fifth solution comprising sodium chloride and ibuprofen lysine (step 302); adjusting a pH level of an exemplary fifth solution between 7.2 and 7.6 (step 304); diluting an exemplary fifth solution to prepare an exemplary diluted fifth solution comprising ibuprofen lysine with a concentration between 90 mg / ml and 110 mg / ml, and sodium chloride with a concentration between 6 mg / ml and 9 mg / ml (step 306); and filtering an exemplary diluted fifth solution (step 308).

[0032] In further detail with respect to step 300, step 300 may include forming an exemplary solution of sodium chloride. In an exemplary embodiment, forming an exemplary solution of sodium chloride may include forming an exemplary solution of sodium chloride with a concentration between 6 gr / ml and 9 mg / ml (with respect to the final concentration of an exemplary solution of sodium chloride). In an exemplary embodiment, forming an exemplary solution of sodium chloride with a concentration between 6 mg / ml and 9 mg / ml (with respect to the final concentration of an exemplary solution of sodium chloride) may include dissolving sodium chloride with a concentration between 6 mg / ml and 9 mg / ml (with respect to the final concentration of an exemplary solution of sodium chloride) in water inexemplary laboratory container including, but not limited to, beakers, tins, flasks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, dissolving sodium chloride with a concentration between 6 mg / ml and 9 mg / ml (with respect to the final concentration of an exemplary solution of sodium chloride) in water in exemplary laboratory container may include adding an exemplary powder of sodium chloride (e.g., using spatula) with a concentration between 6 mg / ml and 9 mg / ml (with respect to the final concentration of an exemplary solution of sodium chloride) and water (e.g., using a sampler, graduated cylinder / tube, etc.) to an exemplary laboratory container, such as a beaker, while stirring using a stirrer, e.g., a magnetic stirrer with a speed range between 200 rpm and 300 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 8 minutes and 15 minutes. In an exemplary embodiment, an exemplary powder of sodium chloride may have a purity of 99 mg / ml.

[0033] In further detail with respect to step 302, step 302 may include forming an exemplary fifth solution comprising sodium chloride and ibuprofen lysine. In an exemplary embodiment, forming an exemplary fifth solution comprising sodium chloride and ibuprofen lysine may comprise forming an exemplary fifth solution comprising sodium chloride with a concentration between 6 mg / ml and 9 mg / ml (with respect to the final concentration of an exemplary fifth solution) and ibuprofen lysine with a concentration between 90-110 mg / ml (with respect to the final concentration of an exemplary fifth solution). In an exemplary embodiment, forming an exemplary fifth solution comprising sodium chloride with a concentration between 6 mg / ml and 9 mg / ml (with respect to the final concentration of an exemplary fifth solution) and ibuprofen lysine with a concentration between 90-110 mg / ml (with respect to the final concentration of an exemplary fifth solution) may include adding ibuprofen lysine with a concentration between 90-110 mg / ml (with respect to the final concentration of an exemplary fifth solution) to an exemplary solution of sodium chloride(i.e., an exemplary solution of sodium chloride set forth in step 300) in exemplary laboratory container including, but not limited to, beakers, tins, flasks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, adding ibuprofen lysine with a concentration between 90-110 mg / ml (with respect to the final concentration of an exemplary fifth solution) to an exemplary solution of sodium chloride (i.e., an exemplary solution of sodium chloride set forth in step 300) in exemplary laboratory container may include adding an exemplary powder of ibuprofen lysine with a concentration between 90- 110 mg / ml (with respect to the final concentration of an exemplary fifth solution) (e.g., using spatula) to an exemplary solution of sodium chloride (i.e., an exemplary solution of sodium chloride set forth in step 300) in an exemplary laboratory container, such as a beaker, while stirring using a stirrer, e.g., a magnetic stirrer with a speed range between 200 rpm and 300 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 8 minutes and 12 minutes.

[0034] In further detail with respect to step 304, step 304 may include adjusting a pH level of an exemplary fifth solution between 7.2 and 7.6. In an exemplary embodiment, adjusting a pH level of an exemplary fifth solution between 7.2 and 7.6 may include measuring a pH level of an exemplary fifth solution and subsequently adding hydrochloric acid or sodium hydroxide (based on the pH level measurement) to an exemplary fifth solution in an exemplary laboratory container, such as a beaker, while stirring using a stirrer, e.g., a magnetic stirrer.

[0035] In further detail with respect to step 306, step 306 may include diluting an exemplary fifth solution to prepare an exemplary diluted fifth solution comprising ibuprofen lysine with a concentration between 90 mg / ml and 110 mg / ml, and sodium chloride with a concentration between 6 mg / ml and 9 mg / ml. In an exemplary embodiment, diluting an exemplary fifth solution to prepare an exemplary diluted fifth solution comprising ibuprofenlysine with a concentration between 90 mg / ml and 110 mg / ml, and sodium chloride with a concentration between 6 mg / ml and 9 mg / ml may include adding water to an exemplary fifth solution in an exemplary laboratory container including, but not limited to, beakers, tins, flasks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, adding water to an exemplary fifth solution in an exemplary laboratory container may include adding water (e.g., using a sampler, graduated cylinder / tube, etc.) to an exemplary fifth solution in an exemplary laboratory container, such as a beaker while stirring using a stirrer, e.g., a magnetic stirrer with a speed range between 200 rpm and 300 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 8 minutes and 15 minutes.

[0036] In further detail with respect to step 308, step 308 may include filtering an exemplary diluted fifth solution. In an exemplary embodiment, filtering an exemplary diluted fifth solution may include passing an exemplary diluted fifth solution through an exemplary syringe filter with a particle size removal between 0.21 micro-meters and 0.23 micro-meters. In an exemplary embodiment, passing an exemplary diluted fifth solution through an exemplary syringe filter with a particle size removal between 0.21 micro-meters and 0.23 micro-meters may result in forming an exemplary second solution comprising ibuprofen lysine with a concentration between 90 mg / ml and 110 mg / ml, and sodium chloride with a concentration between 6 mg / ml and 9 mg / ml.

[0037] In further detail with respect to step 106, step 106 may include forming an exemplary third solution comprising acetazolamide, ibuprofen lysine, sodium hydroxide, and sodium chloride. In an exemplary embodiment, forming an exemplary third solution comprising acetazolamide, ibuprofen lysine, sodium hydroxide, and sodium chloride may include mixing an exemplary first solution (i.e., an exemplary first solution set forth in step 102), and an exemplary second solution (i.e., an exemplary second solution set forth in step104) with a predetermined volume ratio in an exemplary container. In an exemplary embodiment, mixing an exemplary first solution (i.e., an exemplary first solution set forth in step 102), and an exemplary second solution (i.e., an exemplary second solution set forth in step 104) in an exemplary container may include mixing an exemplary first solution (i.e., an exemplary first solution set forth in step 102), and an exemplary second solution (i.e., an exemplary second solution set forth in step 104) with a predetermined volumetric ratio of 1:3 (an exemplary second solution: an exemplary first solution) in exemplary laboratory container including, but not limited to, beakers, tins, flasks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, mixing an exemplary first solution (i.e., an exemplary first solution set forth in step 102), and an exemplary second solution (i.e., an exemplary second solution set forth in step 104) with a predetermined volumetric ratio of 1:3 (an exemplary second solution: an exemplary first solution) in exemplary laboratory container may include adding an exemplary first solution (i.e., an exemplary first solution set forth in step 102), and an exemplary second solution (i.e., an exemplary second solution set forth in step 104) with a predetermined volumetric ratio of 1:3 (an exemplary second solution: an exemplary first solution) (e.g., using a sampler, graduated cylinder / tube, etc.) to an exemplary laboratory container, such as a beaker, while stirring using a stirrer, e.g., a magnetic stirrer with a speed range between 200 rpm and 300 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 8 minutes and 15 minutes.

[0038] In further detail with respect to step 108, step 108 may include adjusting a pH level of an exemplary third solution between 7 and 9.5. In an exemplary embodiment, adjusting a pH level of an exemplary third solution between 7 and 9.5 may include adjusting a pH level of an exemplary third solution between 7 and 9.5 may include measuring a pH level of an exemplary third solution and subsequently adding hydrochloric acid or sodiumhydroxide (based on the pH level measurement) to an exemplary third solution in an exemplary laboratory container, such as a beaker, while stirring using a stirrer, e.g., a magnetic stirrer.

[0039] In further detail with respect to step 110, step 110 may include diluting an exemplary third solution. In an exemplary embodiment, diluting an exemplary third solution may comprise adding water to an exemplary third solution in an exemplary laboratory container including, but not limited to, beakers, tins, flasks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, adding water to an exemplary third solution in an exemplary laboratory container may include adding water (e.g., using a sampler, graduated cylinder / tube, etc.) to an exemplary third solution in an exemplary laboratory container, such as a beaker while stirring using a stirrer, e.g., a magnetic stirrer with a speed range between 60 rpm and 80 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 1 minutes and 10 minutes. In an exemplary embodiment, diluting an exemplary third solution may result in forming an exemplary diluted third solution comprising acetazolamide with a concentration between 22.5 mg / ml and 52.5 mg / ml (with respect to the concentration volume of an exemplary diluted third solution), ibuprofen lysine with a concentration between 4 mg / ml and 20 mg / ml (with respect to the final concentration of an exemplary diluted third solution), and sodium chloride with a concentration between 6 mg / ml and 9 mg / ml (with respect to the final concentration of an exemplary diluted third solution)

[0040] In further detail with respect to step 112, step 112 may include forming an exemplary final solution comprising acetazolamide, ibuprofen lysine, sodium chloride, propylene-glycol and an exemplary preservative. In an exemplary embodiment, forming an exemplary final solution comprising acetazolamide, ibuprofen lysine, sodium chloride, propylene-glycol and an exemplary preservative may include adding an exemplarypreservative and propylene-glycol to an exemplary diluted third solution in exemplary laboratory container including, but not limited to, beakers, tins, flasks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, adding an exemplary preservative and propylene-glycol to an exemplary diluted third solution in exemplary laboratory container may include adding an exemplary preservative comprising benzalkonium chloride with a concentration between 0.08 mg / ml and 0.1 mg / ml (with respect to the final concentration of an exemplary final solution) and propylene-glycol with a concentration between 0.5 mg / ml and 7.5 mg / ml (with respect to the final concentration of an exemplary final solution) in an exemplary laboratory container, such as a beaker, while stirring using a stirrer, e.g., a magnetic stirrer with a speed range between 200 rpm and 300 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 8 minutes and 15 minutes.

[0041] In further detail with respect to step 114, step 114 may include filtering an exemplary final solution comprising acetazolamide, ibuprofen lysine, sodium chloride, propylene glycol and an exemplary preservative. In an exemplary embodiment, filtering an exemplary final solution comprising acetazolamide, ibuprofen lysine, sodium chloride, propylene glycol and an exemplary preservative may include passing an exemplary final solution through an exemplary syringe filter with a particle size removal between 0.42 micrometers and 0.45 micro-meters.EXAMPLES

[0042] Hereinafter, one or more exemplary embodiments will be described in further detail with reference to examples. It will be obvious to a person having ordinary skill in the art that these examples may be for illustrative purposes only and are not to be interpreted to limit the scope of one or more exemplary embodiments.Examplel: Evaluating improvement in sings of obstructive sleep apnea with a clinical trial in patients

[0043] For this purpose, twenty patients with obstructive sleep apnea were included in the clinical trial. These patients were examined with stop bang with an instrument called Viatom CheckmeTRO2 Pulse Oximeter and ALICE NIGHT ONE. Moreover, these patients were evaluated for sleep quality with Pitsburgh Sleep Quality Index (PSQI) and apnea- hypopnea index (AHI). Those patients whom were pregnant or with drug sensitivity, renal failure, and liver failure were excluded from the clinical trial. The nasal spray of the therapeutic composition of the present disclosure were applied in the patients in the clinical trial. For this purpose, the nasal spray of the therapeutic composition of the present disclosure was applied one puff in each nasal cavity every 12 hours a day for 60 days. After 60 days, the assessment described above was performed in the patients. Table 1 below shows the results of the tests in patients at day 0 and 60 after applying the exemplary therapeutic composition, consistence with exemplary embodiments of the present disclosure. As shown in Table 1, the mean O2 saturation was increased in patients after 60 days. Moreover, the mean Score of PSQI, and AHI scale was decreased after 60 days. It is be noted that the mean frequency of stop in breathing during sleep was reduced.Table 1: The results of the tests in patients at day 0 and 60 after applying the exemplary therapeutic composition, consistence with exemplary embodiments of the present disclosure.

[0044] While the foregoing has described what are considered to be the best mode and / or other examples, it is understood that various modifications may be made therein and that the subject matter disclosed herein may be implemented in various forms and examples, and that the teachings may be applied in numerous applications, only some of which have been described herein. It is intended by the following claims to claim any and all applications, modifications and variations that fall within the true scope of the present teachings.

[0045] Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, including in the claims that follow, are approximate, not exact. They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain.

[0046] The scope of protection is limited solely by the claims that now follow. That scope is intended and should be interpreted to be as broad as is consistent with the ordinary meaning of the language that is used in the claims when interpreted in light of this specification and the prosecution history that follows and to encompass all structural and functional equivalents. Notwithstanding, none of the claims are intended to embrace subject matter that fails to satisfy the requirement of Sections 101, 102, or 103 of the Patent Act, nor should they be interpreted in such a way. Any unintended embracement of such subject matter is hereby disclaimed.

[0047] Except as stated immediately above, nothing that has been stated or illustrated is intended or should be interpreted to cause a dedication of any component, step, feature, object, benefit, advantage, or equivalent to the public, regardless of whether it is or is not recited in the claims.

[0048] It will be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their correspondingrespective areas of inquiry and study except where specific meanings have otherwise been set forth herein. Relational terms such as first and second and the like may be used solely to distinguish one entity or action from another without necessarily requiring or implying any actual such relationship or order between such entities or actions. An element proceeded by “a” or “an” does not, without further constraints, preclude the existence of additional identical elements in the process, method, article, or apparatus that comprises the element.

[0049] Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, are approximate, not exact. They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain.

[0050] It will be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their corresponding respective areas of inquiry and study, except where specific meanings have otherwise been set forth herein. Relational terms such as “first” and “second” and the like may be used solely to distinguish one entity or action from another without necessarily requiring or implying any actual such relationship or order between such entities or actions.

[0051] The Abstract of the Disclosure is provided to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. In addition, in the foregoing Detailed Description, it may be seen that various features are grouped together in various implementations. This is for purposes of streamlining the disclosure, and is not to be interpreted as reflecting an intention that the claimed implementations require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed implementation. Thus, thefollowing claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separately claimed subject matter.

[0052] While various implementations have been described, the description is intended to be exemplary, rather than limiting and it will be apparent to those of ordinary skill in the art that many more implementations and implementations are possible that are within the scope of the implementations. Although many possible combinations of features are shown in the accompanying figures and discussed in this detailed description, many other combinations of the disclosed features are possible. Any feature of any implementation may be used in combination with or substituted for any other feature or element in any other implementation unless specifically restricted. Therefore, it will be understood that any of the features shown and / or discussed in the present disclosure may be implemented together in any suitable combination. Accordingly, the implementations are not to be restricted except in light of the attached claims and their equivalents. Also, various modifications and changes may be made within the scope of the attached claims

Claims

What is claimed is:

1. A therapeutic composition for improving the symptoms of obstructive sleep apnea, the therapeutic composition comprising an aqueous solution, the aqueous solution comprising: acetazolamide with a final concentration between 22.5 mg / ml and 52.5 mg / ml; ibuprofen lysine with a final concentration between 4 mg / ml and 20 mg / ml; propylene glycol with a final concentration between 0.5 mg / ml and 7.5 mg / ml; sodium chloride with a final concentration between 6 mg / ml and 9 mg / ml; and a preservative with a final concentration between 0.05 mg / ml and 0.15 mg / ml.

2. The therapeutic composition of claim 1, wherein the preservative is selected from the group consisting of benzalkonium chloride, propyl paraben, methyl paraben, chlorobutanol, and a combination thereof.

3. The therapeutic composition of claim 1, wherein the preservative comprises benzalkonium chloride with a concentration between 0.08 mg / ml and 0.1 mg / ml.

4. A therapeutic nasal drop for improving the symptoms of obstructive sleep apnea, the therapeutic nasal drop comprising an aqueous solution, the aqueous solution comprising: acetazolamide with a final concentration between 22.5 mg / ml and 52.5 mg / ml; ibuprofen lysine with a final concentration between 4 mg / ml and 20 mg / ml; propylene glycol with a final concentration between 0.5 mg / ml and 7.5 mg / ml; sodium chloride with a final concentration between 6 mg / ml and 9 mg / ml; and a preservative comprising benzalkonium chloride with a final concentration between 0.08 mg / ml and 0.1 mg / ml.

5. The therapeutic nasal drop of claim 4, wherein the nasal drop is administered to patients between one drop and 4 drops every 24 hours a day, between one drop and 4 drops every 12 hours a day, between one drop and 4 drops every 6 hours a day, or between one drop and 4 drops every 4 hours a day.

6. A therapeutic nasal spray for improving the symptoms of obstructive sleep apnea, the therapeutic nasal spray comprising an aqueous solution, the aqueous solution comprising: acetazolamide with a final concentration between 22.5 mg / ml and 52.5 mg / ml; ibuprofen lysine with a final concentration between 4 mg / ml and 20 mg / ml; propylene glycol with a final concentration between 0.5 mg / ml and 7.5 mg / ml; sodium chloride with a final concentration between 6 mg / ml and 9 mg / ml; and a preservative comprising benzalkonium chloride with a final concentration between 0.08 mg / ml and 0.1 mg / ml.

7. The therapeutic nasal spray of claim 6, wherein the nasal spray is administered to patients between one puff and 4 puffs every 24 hours a day, between one puff and 4 puffs every 12 hours a day, between one puff and 4 puffs every 6 hours a day, or between one puff and 4 puffs every 4 hours a day.

8. A therapeutic oral spray for improving the symptoms of obstructive sleep apnea, the therapeutic nasal spray comprising an aqueous solution, the aqueous solution comprising: acetazolamide with a final concentration between 22.5 mg / ml and 52.5 mg / ml; ibuprofen lysine with a final concentration between 4 mg / ml and 20 mg / ml; propylene glycol with a final concentration between 0.5 mg / ml and 7.5 mg / ml; sodium chloride with a final concentration between 6 mg / ml and 9 mg / ml; and a preservative comprising benzalkonium chloride with a final concentration between 0.08 mg / ml and 0.1 mg / ml.

9. The therapeutic oral spray of claim 8, wherein the nasal spray is administered to patients between one puff and 4 puffs every 24 hours a day, between one puff and 4 puffs every 12 hours a day, between one puff and 4 puffs every 6 hours a day, or between one puff and 4 puffs every 4 hours a day.

10. A therapeutic nasal drop for improving the symptoms of obstructive sleep apnea, the therapeutic nasal drop comprising an aqueous solution, the aqueous solution comprising: acetazolamide with a final concentration between 22.5 mg / ml and 52.5 mg / ml; ibuprofen lysine with a final concentration between 4 mg / ml and 20 mg / ml; propylene glycol with a final concentration between 0.5 mg / ml and 7.5 mg / ml; sodium chloride with a final concentration between 6 mg / ml and 9 mg / ml; and a preservative comprising benzalkonium chloride with a final concentration between 0.08 mg / ml and 0.1 mg / ml.

11. The therapeutic nasal drop of claim 10, wherein the nasal drop is administered to patients between one drop and 4 drops every 24 hours a day, between one drop and 4 drops every 12 hours a day, between one drop and 4 drops every 6 hours a day, or between one drop and 4 drops every 4 hours a day.

12. A method of producing a therapeutic composition for improving the symptoms of obstructive sleep apnea, the therapeutic composition comprising acetazolamide with a final concentration between 22.5 mg / ml and 52.5 mg / ml; ibuprofen lysine with a final concentration between 4 mg / ml and 20 mg / ml; propylene glycol with a final concentration between 0.5 mg / ml and 7.5 mg / ml; sodium chloride with a final concentration between 6 mg / ml and 9 mg / ml; and a preservative comprising benzalkonium chloride with a final concentration between 0.08 mg / ml and 0.1 mg / ml, the method comprising: forming a first solution comprising acetazolamide and sodium hydroxide with a concentration between 420 mg / ml and 450 mg / ml;forming a second solution comprising ibuprofen lysine with a concentration between 90 mg / ml and 110 mg / ml, and sodium chloride with a concentration between 6 mg / ml and 9 mg / ml; forming a third solution comprising acetazolamide, ibuprofen lysine, sodium hydroxide, and sodium chloride, wherein forming the third solution comprises: mixing the first solution and the second solution with a volume ratio of 1:3 (the second solution: the first solution) while stirring with a speed range between 200 round per minute (rpm) and 300 rpm, at a temperature between 20 oC and 30 oC, and for a time duration between 8 minutes and 15 minutes; adjusting a pH level of the third solution between 7 and 9.5; forming a diluted third solution comprising acetazolamide with a concentration between 22.5 mg / ml and 52.5 mg / ml, ibuprofen lysine with a concentration between 4 mg / ml and 20 mg / ml, and sodium chloride with a concentration between 6 mg / ml and 9 mg / ml, wherein forming the diluted third solution comprises: adding water to the third solution while stirring with a speed range between 60 rpm and 80 rpm, at a temperature between 20 oC and 30 oC, and for a time duration between 1 minutes and 10 minutes; forming a final solution comprising acetazolamide with a final concentration between 22.5 mg / ml and 52.5 mg / ml; ibuprofen lysine with a final concentration between 4 mg / ml and 20 mg / ml; propylene glycol with a final concentration between 0.5 mg / ml and 7.5 mg / ml; sodium chloride with a final concentration between 6 mg / ml and 9 mg / ml; and a preservative comprising benzalkonium chloride with a final concentration between 0.08 mg / ml and 0.1 mg / ml; wherein forming the final solution comprises: adding a preservative comprising benzalkonium chloride with a concentration between 0.08 mg / ml and 0.1 mg / ml (with respect to the final concentration of the final solution) and propylene-glycol with a concentration between 0.5 mg / ml and 7.5 mg / ml(with respect to the final concentration of the final solution) to the diluted third solution; and filtering the final solution comprising acetazolamide, ibuprofen lysine, sodium chloride, propylene glycol and the preservative by passing the final solution through a syringe filter with a particle size removal between 0.42 micro-meters and 0.45 micro-meters.

13. The method of producing a therapeutic composition of claim 12, wherein forming the first solution comprises: forming a solution of acetazolamide with a concentration between 180 mg / ml and 190 mg / ml by dissolving a powder of acetazolamide in water; forming a fourth solution comprising acetazolamide with a concentration between 930 mg / ml and 950 mg / ml, and sodium hydroxide with a concentration between 540 mg / ml and 560 mg / ml by mixing the solution of acetazolamide and a solution of sodium hydroxide (with a concentration of about 8 mg / ml) with a volumetric ratio of 1: 1 (the solution of acetazolamide: the solution of sodium hydroxide) while stirring with a speed range between 60 rpm and 80 rpm, at a temperature between 25 °C and 30 °C, and for a time duration between 1 minutes and 5 minutes; forming a porous powder comprising acetazolamide and sodium hydroxide by freeze-drying the fourth solution at a temperature level between 48 °C and 52 °C, and for a time duration between 50 minutes and 70 minutes; forming a first mixture comprising the porous powder with a concentration between 14.9 mg / ml and 29.8 mg / ml by dissolving the porous powder in water while stirring with a speed range between 60 rpm and 80 rpm, at a temperature between 25 °C and 30 °C, and for a time duration between 1 minutes and 2 minutes; adjusting a pH level of the first mixture between 7 and 8; andforming a diluted first mixture comprising acetazolamide with a concentration between 70 mg / ml and 80 mg / ml and sodium hydroxide with a concentration between 420 mg / ml and 450 mg / ml by adding water to the first mixture.

14. The method of producing a therapeutic composition of claim 12, wherein forming the second solution comprises: forming a solution of sodium chloride with a concentration between 6 gr / ml and 9 mg / ml by dissolving sodium chloride with a concentration between 6 mg / ml and 9 mg / ml in water while stirring with a speed range between 200 rpm and 300 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 8 minutes and 15 minutes; forming a fifth solution comprising sodium chloride with a concentration between 6 mg / ml and 9 mg / ml and ibuprofen lysine with a concentration between 90-110 mg / ml by adding ibuprofen lysine to the solution of sodium chloride while stirring with a speed range between 200 rpm and 300 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 8 minutes and 12 minutes; adjusting a pH level of the fifth solution between 7.2 and 7.6; forming a diluted fifth solution comprising ibuprofen lysine with a concentration between 90 mg / ml and 110 mg / ml, and sodium chloride with a concentration between 6 mg / ml and 9 mg / ml by adding water to the fifth solution while stirring with a speed range between 200 rpm and 300 rpm, at a temperature between 20 °C and 30 °C, and for a time duration between 8 minutes and 15 minutes; and filtering the diluted fifth solution by passing the diluted fifth solution through a syringe filter with a particle size removal between 0.21 micro-meters and 0.23 micro-meters.

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