Abstract:
An aqueous, flavored, topical, nasal decongestant composition containing an amount of oxymetazoline or a pharmaceutically acceptable salt thereof e.g., oxymetazoline HCl sufficient to effect nasal decongestion and an amount of a fruity flavor e.g. cherry flavor, sufficient to mask the medicinal after-taste of the composition, together with an aqueous carrier.

Description:
This is a division of application Ser. No. 423,075, filed Oct. 18, 1989 now U.S. Pat. No. 4,970,240. 
    
    
     BACKGROUND 
     This invention relates to an aqueous, flavored, topical, nasal decongestant composition containing oxymetazoline or a pharmaceutically acceptable salt thereof, an aqueous carrier and sufficient fruity flavor to mask the medicinal after-taste of the composition. 
     Aqueous, topical, nasal decongestant compositions containing oxymetazoline hydrochloride, the longest acting nasal decongestant currently available, are applied to the nasal passages of mammals especially human beings to affect temporary relief of nasal congestion associated with colds, hay fever and sinusitis. Menthol flavored nasal decongestant compositions containing vapors of menthol, eucalyptol and camphor and polysorbate in addition to oxymetazoline hydrochloride and an aqueous carrier are available as OTC products under the tradename AFRIN® nasal spray from Schering Corporation, Kenilworth, N.J. However, such menthol flavored or unflavored nasal decongestant composition when applied to the nasal passages, causes a bitter medicinal after-taste. 
     T. M. Berman (New England Journal of Medicine, Aug. 23, 1979, Vol. 301, p 437) discloses addition of peppermint flavor to improve the taste of lidocaine used to anesthetize the pharynx and nasal passage before bronchoscopy. D. E. Hornung et al. (Ann. N.Y. Acad. Sci., 1987, Vol. 510, pp 86-90) disclose smell-taste perception in general terms. Neither reference discloses or suggests the present invention. 
     SUMMARY OF THE INVENTION 
     We have surprisingly discovered that addition of small amounts of fruity flavors to aqueous topical nasal decongestant compositions containing oxymetazoline hydrochloride in an aqueous base effectively masks the medicinal after-taste of the decongestant composition. Accordingly, the present invention provides an aqueous, flavored, topical nasal, decongestant composition comprising an amount of oxymetazoline or a pharmaceutically acceptable salt thereof sufficient to effect nasal decongestion and an aqueous carrier and an amount of a fruity flavor sufficient to mask the medicinal after-taste of the topical nasal decongestant composition. The present invention also provides an aqueous, flavored, topical nasal decongestant composition comprising an amount of oxymetazoline or a pharmaceutically acceptable salt thereof sufficient to effect nasal decongestion and an aqueous carrier containing: 
     about 4.0 to about 7.0% by weight of 70% (w/v) sorbitol solution; 
     about 0 to about 0.025% by weight of at least one antimicrobial preservative; 
     about 0.005 to about 0.5% by weight of a fruity flavor, and an amount of a pharmaceutically acceptable base and buffer sufficient to maintain the pH of the composition within the range of about 4.0 to about 6.5, and water. The present invention further provides a method of treating nasal congestion by administering to a nasal passage of a patient with nasal congestion an aqueous, fruity-flavored, topical nasal decongestant composition of the present invention. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The fruity flavors found suitable for use in the present invention include cherry, strawberry, peach and vanillin all of which are flavors approved for use in drugs by the United States FDA. The amount of fruity flavor found sufficient to mask the medicinal after-taste of the topical nasal decongestant compositions of the present invention is within the range of about 0.005 to about 0.5% by weight of the composition. The ranges for individual fruity flavors are given in the table below. 
     
         ______________________________________      Concentration Range                   Percent by Weight ofFruity Flavor        mg/mL      Composition______________________________________Cherry       0.1-4.0    0.0-1 to 0.4Strawberry   0.05-5     0.005 to 0.5Peach        0.1-3      0.01 to 0.3Vanillin     0.1-3      0.01 to 0.3______________________________________ 
    
     The use of cherry flavor (preferably about 3.5 mg/mL) or strawberry (preferably about 4.0 mg/mL) in the compositions and methods of the present invention is preferred. 
     The amount of oxymetazoline or pharmaceutically acceptable salt thereof found sufficient to effect nasal decongestion is in the range of about 0.01% to about 0.1% by weight of the topical nasal decongestant composition. Typically, 0.025% by weight oxymetrazoline (as the HCl) is suitable for children 2 to 5 years of age and 0.05% by weight of oxymetazoline (also as the HCl salt) is suitable for adults and children above five years of age. Oxymetazoline HCl is commercially available from Schering Labs, Kenilworth, N.J. See also The Merck Index, Tenth Edition, 1983 p. 6838. By the term &#34;pharmaceutically acceptable salt&#34; as used herein is meant the acid addition salt formed by admixing oxymetazoline with a pharmaceutically acceptable acid such as HCl, HF, H 2  SO 4 , HNO 3 , malonic, succinic, trifluoroacetic acids and the like. 
     The compositions of the present invention contains at least one antimicrobial preservative in the range of 0% to about 0.025% by weight of the composition. Typical suitable preservatives function as antimicrobial agents and include the commercially available preservatives, e.g. phenyl mercuric acetate in the range of about 0 to about 0.005% by weight, benzalkonium chloride in the range of about 0 to about 0.02% by weight or thimerosal in the range of about 0.001 to about 0.01% by weight. 
     The compositions of the present invention contain a sorbitol solution (70% w/v) normally present in the range of about 4.0 to 7.0% by weight. Sorbitol solution is a tonicity agent which renders the composition of the present invention isotonic with the body&#39;s fluids. Other concentrations of sorbitol and other tonicity agents well known to those skilled in the art are contemplated to be within the scope of this invention. 
     The compositions of the present invention also include pharmaceutically acceptable buffers and pharmaceutically acceptable bases sufficient to adjust and maintain the pH of the compositions of the present invention in the range of about 4.0 to about 6.5, preferably about 5.5 to about 6.5. Typically suitable buffers include citrate, phosphate and glycine. Typically suitable bases include alkali metal hydroxides, especially NaOH. 
     The compositions of the present invention may be formulated for use by adults or children in the form of nose drops, or spray. A spray pump or plastic squeeze bottle may be use for the spray. The dosage and administration regimen of Schering Corporation AFRIN® nasal spray in the 1988 edition of the PDR for NON-PRESCRIPTION DRUGS at page 685 may be followed. 
     EXAMPLE 1 
     Adult Strength Flavored Product 
     
         ______________________________________            ConcentrationIngredient         mg/mL     % by wgt.______________________________________Oxymetazoline HCl  0.50      .05Phenylmercuric Acetate              0.02      .002Benzalkonium Chloride              0.20      .02Glycine            3.754     .375470% (w/v) Sorbitol Solution              57.143    5.7143Cherry Flavor      3.5       .35Sodium Hydroxide to adjust              --        --pH to within range of 5.5 to 6.5Water Purified USP q.s to 1 mL______________________________________ 
    
     METHOD OF PREPARATION 
     1) Dissolve the oxymetazoline HCl, phenyl mercuric acetate, benzalkonium chloride, glycine, 70% (w/v) sorbitol solution, and cherry flavor into a volume of purified water sufficient to provide a homogeneous solution. Adjust the pH of the so-formed solution to 5.5 to 6.5 using a sodium hydroxide solution. Add sufficient purified water to the final volume (1 mL) having the ingredient concentrations listed above. Filter the solution. 
     Strawberry (4 mg/mL) may be substituted for cherry flavor in the above formulation. 
     Fill into 15 or 30 mL plastic squeeze bottles or 15 mL pump spray bottles or 20 mL dropper bottles. 
     EXAMPLE 2 
     Children&#39;s Strength Flavored Product 
     Follow the procedure of Example 1 but use 0.25 mg/mL of oxymetazoline HCl in the formulation instead of 0.50 mg/ml. 
     EXAMPLE 3 
     Exemplary Formulations 
     
         ______________________________________              ConcentrationIngredients          mg/mL     % by wgt.______________________________________Oxymetazoline        0.01-0.1  0.001-0.01Phenylmercuric acetate                0-0.05    0-0.005Benzalkonium Chloride                0-0.2     0-0.0270% (w/v) Sorbitol Solution                40-70     4.0-7.0Fruity Flavor        0.05-5    0.005-0.5Buffer and NaOH sufficient to adjustand maintain pH in the range of5.5 to 6.5Water                q.s to 1 ml______________________________________ 
    
     The composition of Example 1 in the form of a nasal spray was tested and found to have no medicinal after-taste.