WO2002056876A2

WO2002056876A2 - Treatment for snoring

Info

Publication number: WO2002056876A2
Application number: PCT/US2002/001353
Authority: WO
Inventors: Thomas Alan Halvorson
Original assignee: Medpointe Healthcare Inc.
Priority date: 2001-01-18
Filing date: 2002-01-17
Publication date: 2002-07-25
Also published as: AU2002236781A1; WO2002056876A3

Abstract

Use of an antihistamine, in particular azelastine (or salt thereof) for alleviating snoring.

Description

TREATMENT FOR SNORING

This application claims the priority of United States Provisional Application Serial No. 60/262,449, filed January 18, 2001.

Field Of The Invention

The field of the present invention relates generally to methods for reducing snoring, and more specifically to a method for reducing nasal congestion in the treatment of snoring.

Summary Of The Invention

The present invention provides a method for treating snoring that in some cases eliminates snoring entirely, and in other cases reduces the intensity and frequency of snoring. The treatment includes the step of administering a prescribed dosage in one or more doses per day of an antihistamine, preferably an antihistamine that is a histamine H1 receptor antagonist. In a particularly preferred embodiment the antihistamine is azelastine or a physiologically acceptable salt thereof. The chemical designation is: 4-(4-chlorobenzyl)-2- (perhydro-1-methyl- azepine-4-yl)-1-(2H)phthalazinone.

The antihistamine is preferably topically applied to the nasal passage, generally in the form of a nasal spray.

The antihistamine is administered in an amount effective to inhibit snoring and may be administered once or more than once a day. In a preferred embodiment, at least one dose is administered prior to bedtime.

The preferred embodiment of the invention is a sterile and stable aqueous solution of azelastine or one or more of its salts which can be used in the form of drops, ointments, creams, gels, insufflatable powders or, in a particularly preferred embodiment, in the form of a spray (preferably a nasal spray). The spray can be formed by the use of a conventional spray-squeeze bottle or a pump vaporizer. In addition, it is also possible to use compressed gas aerosols. For example, 0.03 to 3 mg of azelastine base should be released per individual actuation. , Solvents which may preferably be used for the formulations of the invention are: water, saturated aliphatic mono and polyvalent alcohols which contain 2-3 carbon atoms (for example ethanol. Isopropanol, 1 ,2-propylene glycol, glycerine), liquid polyglycols (molecular weight 200 to 600).

The solvent used is preferably water or mixtures of water with other physiologically acceptable solvents (for example those mentioned above). Preferably, the amount of the latter solvent in the aqueous mixture should not exceed 15% by weight.

The solutions or formulations preferably contain preservatives and stabilizers. These include, for example: ethylene diamine tetra-acetic acid (eidetic acid) and their alkali salts (for example dialkali salts such as disodium salt, calcium salt, calcium- sodium salt), lower alkyl p-hydroxybenzoates, chlorohexidine (for example in the form of the acetate or gluconate), phenyl mercury borate. Furthermore, it is possible, for example, to use sodium -(2-ethylmercurithio)-benzoate generally known as "thimerosal" which may be present in an amount of 0.001 to 0.05, preferably from 0.005 to 0.02, for example 0.01% (weight/volume in liquid formulations, otherwise weight/weight). Other suitable preservatives are: pharmaceutically useful quaternary ammonium compound, for example cetylpyridinium chloride, tetradecyltrimethyl ammonium bromide, generally known as "cetrimide", benzyldimethyl-[2-[2-[p- (1 ,1 ,3,3-tetramethyl-butyl)]phenoxy]ethoxy]-ammonium chloride, generally known as "benzethonium chloride" and myristy -picolinium chloride. Each of these compounds may be used in a concentration of 0.002 to 0.05, for example 0.02% (weight/volume in liquid formulations, otherwise weight/weight). Preferred preservatives among the quaternary ammonium compounds are, however, alkylbenzyl dimethyl ammonium chloride and mixtures thereof, for example the compounds generally known as "benzalkonium chloride".

The formulations of the invention (solutions, suspensions as well as oily solutions or suspensions, ointments, emulsions, creams, gels, dosage aerosols) contain 0.0005 to 2, preferably 0.001 to 1 , in particular 0.003 to 0.5% (weight/weight) of azelastine (related to the free azelastine base). Should azelastine be present-as a salt, the amounts should be recalculated as necessary to give the amounts of azelastine itself mentioned above.

In the case of powders, the concentration of azelastine base is 0.0005 to 2 percent by weight related to the solid carrier substances. In the case of solutions, the dosage per nostril is, for example, 0.01 to 0.2 ml, in particular 0.05 to 0.15 ml. Such a dosage should be applied once to several times, preferably 1 to 5 times daily (optionally also hourly).

Possible acid components for azelastine salts are, for example: hydrophilic acids (HC1 , HBr), sulfuric acid, phosphoric acids), nitric acid, organic mono-, di-or thcarboxylic acids of aliphatic, alicyclic, aromatic or heterocyclic organic acids (embonic acid, citric acid, tartaric acid), aliphatic and aromatic sulfonic acids (for example camphorsulfonic acid).

It is also possible to add to the formulations buffer substances such as citric acid/sodium hydrogensulphate borate buffer, phosphates (sodium hydrogenorthophosphate, disodium hydrogenphosphate), tromethamol or equivalent conventional buffers in order, for example, to adjust the formulation to a pH value of 6 to 7.5, preferably 6.5 to 7.1.

In a particularly preferred embodiment snoring is treated by use of a 0.1 % aqueous solution of azelastine hydrochloride, preferably as a nasal spray. The spray is metered to deliver about 137 meg of azelastine hydrochloride (equivalent to 125 meg of azelastine base).

Example 1

Nasal spray or nasal drops with 0.1% azelastine hydrochloride as active ingredient.

The following are dissolved, in the following order, into 9.00 kg of water: 10 g of azelastine hydrochloride, 5 g of eidetic acid disodium salt. 2 H₂0, 68 g of sodium chloride, 1.25 g of alkyl-benzyldimethylammonium chloride (benzalkonium chloride), 4.38 g of citric acid, 64.8 g of sodium monohydrogen-phosphate. 12 H₂0 as well as 10 g of hydroxypropylmethyl cellulose.)

The solution obtained is diluted to 10.05 kg = 10 liters with water. The solution is filtered through a membrane filter of pore size 0.2 μm after careful mixing, the first 500 ml of filtrate being discarded. The filtrate has a pH value of 6.8 ±0.3. This is filled into plastic bottles which are closed with a conventional spray insert or into plastic or glass bottles which are closed with a conventional pump sprayer. In the latter case, pumps with nasal spray inserts are, for example used, which spray about 0.14 ml of solution per actuation. In this manner, 0.14 mg of azelastine hydrochloride are sprayed into the nose per actuation in the form of the solution. • If the above obtained filtrate is filled into the bottles with dropper pipettes conventionally used for nasal drops or eye drops, the solution can be dripped into the nose or eye using a dropper pipette.

Example 2 The following is an example of a bulk nasal solution, that is diluted with water to produce a 0.1% solution of azelastine hydrochloride.

In general, a patient in need of treatment for snoring is treated with an antihistamine in particular azelastine or pharmaceutically acceptable salt thereof in an amount effective for such treatment. For example, topical treatment with an amount of azelastine base equivalent to that of one to two sprays to each nostril, twice daily, using the hereinabove described 0.1% aqueous solution of azelastine hydrochloride. Other amounts should be apparent to those skilled in the art from the teachings herein.

Numerous modifications and variates of the present inventor are possible in light of the above teachings; therefore within the appended claims the invention may be practical otherwise than as particularly described.

Claims

What is claimed is:

1. A method for treating snoring in a patient need thereof, comprising: treating said patient by topically administering to the nasal passage an effective amount of an antihistamine.

2. The method of claim 1 wherein the antihistamine is azelastine or a physiologically acceptable salt thereof.

3. The process of claim 2 wherein the antihistamine is in a nasal spray.

4. Manufacture of a composition containing an antihistamine for use in treating snoring in a patient in need thereof.