HK1027029A - Topical nasal antiinflammatory compositions - Google Patents

Description

Topical nasal anti-inflammatory composition

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Background

Topical nasal anti-inflammatory formulations are known in the field of treatment of nasal mucositis, particularly in the symptomatic relief of nasal and sinus conditions such as rhinitis. However, nasal and sinus conditions may be characterized by variable symptoms that require treatment with multiple therapeutic agents. For example, allergic rhinitis may be characterized by rhinorrhea, nasal itching, sneezing, congestion, and post nasal drip, and thus may require treatment with antihistamines, decongestants, anti-allergic agents, and anesthetics, in addition to anti-inflammatory agents.

The use of multiple topical nasal formulations to administer multiple therapeutic agents has significant drawbacks. The volume of fluid that can be effectively nasally administered is limited by the surface area of the nostrils and the biological adhesiveness of the fluid. In addition, sufficient contact between the topical formulation and the surface area of the nostril is required to ensure adequate therapeutic agent dosing. Furthermore, sprays require a threshold surface tension to form droplets. Thus, the volume released per operation is limited to the volume remaining in the nostril that is not prematurely discharged. Thus, multiple topical nasal formulations cannot be effectively administered simultaneously.

Another disadvantage of the administration of many topical nasal formulations is the inconvenience experienced by the patient. The inconvenience of administering multiple spray products or nasal drops can compromise patient compliance. Patients complain that excess spray flows into their throat and is able to detect the taste, requiring a flavoring to mask the bitter medication.

Thus, there is a need for a convenient means for nasal administration of a variety of therapeutic agents.

Summary of The Invention

The present invention provides a topically applicable nasal composition comprising a therapeutically effective amount of a topical anti-inflammatory agent and a therapeutically effective amount of at least one agent suitable for topical nasal administration selected from the group consisting of vasoconstrictors, neuraminidase inhibitors, anticholinergics, leukotriene inhibitors, antihistamines, anti-allergic agents, anesthetics, and mucolytics.

Detailed description of the invention

The present invention provides topically administrable nasal compositions comprising a topical anti-inflammatory agent and at least one additional therapeutic agent. The composition can be used for treating nasal and sinus diseases, such as allergic rhinitis or common cold.

The topical anti-inflammatory agent in the compositions of the present invention is a corticosteroid known in the art to inhibit inflammation. In a preferred embodiment, the topical anti-inflammatory agent is beclomethasone dipropionate, budesonide, dexamethasone, mometasone furoate, fluticasone propionate or triamcinolone acetonide. The compositions contain a therapeutically effective amount of a selected anti-inflammatory agent. One of ordinary skill in the art will be able to determine the amount of a treatment effective to inhibit inflammation. The precise amount will depend on the method of administration and the age, weight and condition of the subject. Generally, the amount of anti-inflammatory agent is known in the art and is therapeutically effective when administered nasally.

The compositions of the present invention further comprise at least one additional therapeutic agent, such that the anti-inflammatory agent and the at least one additional therapeutic agent are conveniently administered in a single topical nasal composition. The additional therapeutic agent is suitable for local nasal administration and is selected from the group consisting of vasoconstrictors, neuraminidase inhibitors, leukotriene inhibitors, anticholinergics, antihistamines, antiallergic agents, local anesthetics, and mucolytics. The use of additional therapeutic agents in combination with anti-inflammatory agents provides additive and synergistic effects in the treatment of nasal and sinus conditions.

Vasoconstrictors suitable for topical nasal administration in the compositions of the present invention are oxymetazoline, naphazoline, xylometazoline and phenylephrine. Leukotriene inhibitors include zafirlukast (zafirlukast), a selective, competitive receptor antagonist of the three leukotrienes C4, D4, and E4; pranserte, a selective, competitive receptor antagonist of D4; and zibaitong, which is a leukotriene inhibitor. Neuraminidase inhibitors include zanamivir (Zanamivir) (GG-167). Suitable antihistamines include diphenhydramine, chlorpheniramine, cetirizine, terfenadine, fexofenadine (fenoxadine), astemizole, norastemizole, azo  statin, and azatidine (azatidine). The antiallergic agent comprises cromolyn sodium, nedocromil and levocabastine. An anticholinergic agent that can be used in the compositions of the present invention is ipratropium bromide. Local anesthetics include dyclonine, pramoxine, and benzocaine. Mucolytic agents suitable for topical nasal administration are acetylcysteine, guaifenesin and carbocysteine (mucocysteine). The therapeutically effective amount of such agents can be determined by one of ordinary skill in the art, based on the known use of such agents, and taking into account the method of administration and the age, weight, and condition of the subject.

The compositions of the present invention are formulated as an aqueous solution comprising an anti-inflammatory agent and at least one additional therapeutic agent, further comprising a pharmaceutically acceptable nasal carrier. The formulation of pharmaceutical compositions is generally known in the art and may be conveniently referred to standard textbooks, for example, Remington pharmaceutical sciences 1985, 17 th edition, Mack Publishing co.

Preferred nasal formulations are nasal drops or nasal sprays containing an aqueous solution buffered with water as a carrier. The composition is preferably isotonic. Isotonic agents are known in the art, such as sugars and sodium chloride, may be included in the compositions.

The compositions of the present invention may also contain a humectant to increase viscosity, increase moisture and ciliary activity. Suitable humectants include glycerin, polyethylene glycol, propylene glycol, and mixtures thereof.

Additives are known in the art and include pharmaceutically acceptable preservatives, stabilizers, flavoring agents and pH adjusting agents, and may also be included in the compositions of the present invention.

Another embodiment of the invention provides a preservative-free composition comprising an anti-inflammatory agent and at least one additional therapeutic agent. Preservative-free compositions are preferred due to reduced sensitivity and improved patient acceptance. They can be made into unit dose or system, preventing the contamination of the solution in storage.

The compositions of the present invention may conveniently be administered nasally to humans in dosage unit form to achieve the desired therapeutic effect of the above-mentioned anti-inflammatory agents and additional therapeutic agents. The composition can be administered in the form of a nasal spray or nasal drops. Nasal sprays can be provided in the form of squeeze bottles or metered dose manual nasal spray pumps, designed to deliver the desired dose by one or two sprays, for example. The compositions may also be administered as an aerosol spray, for example a metered dose pressurized aerosol, containing a propellant, such as a halogenated hydrocarbon.

Claims (16)

1. A topically applicable nasal composition comprising a therapeutically effective amount of a topical anti-inflammatory agent and a therapeutically effective amount of at least one agent suitable for topical nasal administration selected from the group consisting of vasoconstrictors, neuraminidase inhibitors, anticholinergics, leukotriene inhibitors, antihistamines, anti-allergic agents, anesthetics, and mucolytics.

2. The composition of claim 1, wherein said topical anti-inflammatory agent is selected from the group consisting of beclomethasone dipropionate, budesonide, dexamethasone, mometasone furoate, fluticasone propionate and triamcinolone acetonide.

3. The composition of claim 1, wherein the vasoconstrictor is selected from the group consisting of oxymetazoline, naphazoline, xylometazoline, and phenylephrine.

4. The composition of claim 1, wherein said antihistamine is selected from the group consisting of diphenhydramine, chlorpheniramine, terfenadine, azo  statin, norastemizole, fexofenadine (fexofenadine), cetirizine, astemizole, and azatidine.

5. The composition of claim 1, wherein said anti-allergic agent is selected from the group consisting of cromolyn sodium, levocabastine, and nedocromil.

6. The composition of claim 1, wherein said anticholinergic is ipratropium.

7. The composition of claim 1, wherein said local anesthetic is selected from the group consisting of dyclonine, pramoxine and benzocaine.

8. The composition of claim 1, wherein the mucolytic agent is selected from the group consisting of acetylcysteine, guaifenesin, and carbocysteine.

9. The composition of claim 1, wherein the leukotriene inhibitor is selected from the group consisting of zafirlukast, pranlukast, and zileuton.

10. The composition of claim 1, wherein the neuraminidase inhibitor is zanamitra.

11. A topically applicable nasal composition comprising a therapeutically effective amount of a topical anti-inflammatory agent selected from the group consisting of beclomethasone dipropionate, budesonide, dexamethasone, mometasone furoate, fluticasone propionate and triamcinolone acetonide, and a therapeutically effective amount of at least one agent selected from the group consisting of oxymetazoline, phenylephrine, diphenhydramine, chlorpheniramine, terfenadine, astemizole, azatidine, cromolyn sodium, nedocromil, ipratropium bromide, dyclonine, benzocaine, acetylcysteine, guaifenesin and carbocysteine.

12. The composition of claim 1 or 11, further comprising at least one humectant.

13. The composition of claim 12 wherein said humectant is selected from the group consisting of glycerin, polyethylene glycol, and propylene glycol.

14. The composition of claim 1 or 11, comprising a pharmaceutically acceptable carrier.

15. A composition according to claim 1 or 11, formulated for administration as a nasal spray.

16. The composition of claim 1 or 11, formulated for nasal administration.