Title of Invention

A LIQUID NASAL PHARMACEUTICAL COMPOSITION

Abstract

The present invention relates to- a liquid nasal pharmaceutical composition which comprises (a) one or more active substances suitable for nasal administration and selected from the group consisting of vasoconstrictors, antiallergic agents and corticosteroids, (b) sorbitol; (c) a water-solubleC1-C4-alkyl-cellulose derivative; (d) a vehicle which is present in an amount of' at least 90% (m/V) of the total composition, and which is selected from water and mixtures of water with propylene glycol, water with glycerol and water with both propylene glycol and glycerol, whereby in all said mixtures water is present in an amount of at least 95% (m/V); and (e) optionally one or more nasally acceptable excipients.

Full Text

The present invention relates to a liquid nasal pharmaceutical composition. More specifically, it concerns liquid nasal formulations with improved moisturizing properties. The nasal administration of active substances is a widely used method of treatment. Active substances which come into consideration are, for example, vasoconstrictors, such as xylometazoline, or antiallergic agents, such as cromoglycic acid or H1 receptor antagonists, e.g. dimethindene maleate. Another group of possible active substances is e.g. corticosteroids, such as beclomethasone or fluticasone. The indications in which a certain nasally administered drug is to be applied are known in the art. For example, vasoconstrictors are e.g. used as nasal decongestants for alleviating the typical symptoms of common cold, like running nose, obstructed nose etc., or in rhinitis or sinusitis. Antiallergic agents and corticosteroids are e.g. used in antiallergic conditions, e.g. hay fever, or in anti-asthmatic or anti-inflammatory conditions. Nasal administration of active substances in liquid form, e.g. in the form of drops, a solution or a spray - opposite to nasal administration in gel form - is desirable inter alia because of a much better distribution of the active substances within the - partly tiny - nasal cavities and an easier handling and dosing, e.g. in pediatric or geriatric patients. However, upon administration of liquid nasal formulations often the patients are suffering from side-effects like burning, dryness, stinging of the nasal mucosa or sneezing. One of the reasons for this is that liquids - in contrast to gels - normally do not remain in the nasal cavities for a long period of time but are washed out fast. The present invention addresses these problems and provides liquid nasal formulations which do not only moisturize the nasal mucosa but also keep it sufficiently moisturized for a prolonged period of time. As a result, liquid nasal pharmaceutical compositions having excellent and prolonged moisturizing properties are obtained. WE CLAIM: 1. A liquid nasal pharmaceutical composition which comprises (a) one or more active substances suitable for nasal administration and selected from the group consisting of vasoconstrictors, antiallergic agents and corticosteroids, (b) sorbitol; (c) a water-soluble C1-C4alkyl-cellulose derivative; (d) a vehicle which is present in an amount of at least 90% (m/V) of the total composition, and which is selected from water and mixtures of water with propylene glycol, water with glycerol and water with both propylene glycol and glycerol, whereby in all said mixtures water is present in an amount of at least 95% (m/V); and (e) optionally one or more nasally acceptable excipients. 2. The pharmaceutical composition according to claim 1, wherein the active substance (a) is selected from the group consisting of vasoconstrictors and antiallergic agents. 3. The pharmaceutical composition according to claim 1, wherein the active substances (a) represent a combination of a vasoconstrictor and an antiallergic agent. 4. The pharmaceutical composition according to claim 1, wherein the active substance (a) is selected from the group of vasoconstrictors consisting of xylometazoline, naphazoline, fenoxazoline, oxymetazoline, tetrahydrozoline, tramazoline, phenylephrine, ephedrine, epinephrine, and a nasally acceptable salt of any of these compounds. 5. The pharmaceutical composition according to claim 1, wherein the active substance (a) is selected from the group of vasoconstrictors consisting of xylometazoline, oxymetazoline and a nasally acceptable salt of any of these two compounds. 6. The pharmaceutical composition according to any one of claims 1 to 5, wherein sorbitol (b) is present in an amount of from 0.5 up to 5% (m/V) of the total composition. 7. The pharmaceutical composition according to any one of claims 1 to 6, wherein the water-soluble C1-C4-alkyl-cellulose derivative is selected from the group consisting of methyl cellulose and (hydroxy or carboxy)-substituted C-C4-alkyl-celluloses. 8. The pharmaceutical composition according to any one of claims 1 to 6, wherein the water-soluble C-C4-alkyl-cellulose derivative (c) is hydroxypropyl methyl cellulose. 9. The pharmaceutical composition according to any one of claims 1 to 8, wherein the water-soluble C1-C4-alkyl-cellulose derivative (c) is present in an amount of from 0.3 up to 1 % (m/V) of the total composition. 10. The pharmaceutical composition according to any one of claims 1 to 9, wherein the vehicle (d) is water. 11. The pharmaceutical composition according to any one of claims 1 to 10, which contains as nasally acceptable excipients (e) essentially the following components: sodium dihydrogen phosphate dihydrate and disodium phosphate dodecahydrate as buffering agents, disodium edetate as chelating agent, benzalkonium chloride as preservative, and sodium chloride as isotonicity regulator. 12. The pharmaceutical composition according to any one of claims 1 to 11, which contains as nasally acceptable excipients (e) essentially the following components: 0.3-0.7% sodium dihydrogen phosphate dihydrate and 0.12-0.25% disodium phosphate dodecahydrate as buffering agents, 0.02-0.08% disodium edetate as chelating agent, 0.005-0.02% benzalkonium chloride as preservative, and 0.20-0.60% sodium chloride as isotonicity regulator. 13. The pharmaceutical composition according to any one of claims 1 to 4 and 6 to 12, which consists essentially of 0.025-0.2% of one or more vasoconstrictors selected from the group consisting of xylometazoline, naphazoline, fenoxazoline, oxymetazoline, tetrahydrozoline, tramazoline, phenylephrine, ephedrine, epinephrine, and nasally acceptable salts of said compounds; 1.2-1.6% sorbitol, 0.3-0.7% hydroxypropyl methyl cellulose, 0.3-0.7% sodium dihydrogen phosphate dihydrate, 0.12-0.25% disodium phosphate dodecahydrate, 0.02-0.08% disodium edetate, 0.005- 0.02% benzalkonium chloride and 0.20-0.60% sodium chloride, the remainder being water. 14. The pharmaceutical composition according to claim 13, wherein the vasoconstrictor selected is xylometazoline hydrochloride. 15. The pharmaceutical composition according to any one of claims 1 to 14, which is in the form of drops, a solution, a spray or a metered-dose spray.

Documents:

in-pct-2000-075-che-abstract.pdf

in-pct-2000-075-che-claims filed.pdf

in-pct-2000-075-che-claims grand.pdf

in-pct-2000-075-che-correspondence others.pdf

in-pct-2000-075-che-description complete filed.pdf

in-pct-2000-075-che-form 1.pdf

in-pct-2000-075-che-form 26.pdf

in-pct-2000-075-che-form 3.pdf

in-pct-2000-075-che-form 5.pdf

in-pct-2000-075-che-other documents.pdf

in-pct-2000-075-che-pct.pdf

in-pct-2000-75-che-correspondence po.pdf

in-pct-2000-75-che-description complete-grant.pdf