WO1994014476A1

WO1994014476A1 - Use of s(+) antipodes of analgesic agents for the manufacture of a composition to treat respiratory disorders

Info

Publication number: WO1994014476A1
Application number: PCT/US1993/012022
Authority: WO
Inventors: Richard Wilfred D'souza; Sekhar Mitra; Michael James Simone
Original assignee: The Procter & Gamble Company
Priority date: 1992-12-21
Filing date: 1993-12-09
Publication date: 1994-07-07
Also published as: EP0674527A1; JPH08506808A; MX9400040A; CA2151912A1

Abstract

The present invention relates to compositions and methods for providing improved treatment, management or mitigation of cold, cold-like and/or flu symptoms by administering a safe and effective amount of a composition comprising an analgesic agent substantially free or of its R(-) antipode selected from the group consisting of (S+)-ibuprofen, (S+) flurbiprofen and (S+) ketoprofen, pharmaceutically-acceptable salts thereof, and mixtures thereof along with at least one of (a) a decongestant, (b) an expectorant and (c) and antitussive.

Description

(+) ANTIPODES OF ANALGESIC AGENTS FOR THE MANUFACTURE OF A COMPOSITI RESPIRATORY DISORDERS.

TECHNICAL FIELD

The present invention relates to compositions and methods for providing improved treatment, management or mitigation of cold, cold-like and/or flu symptoms by administering a safe and effective amount of a composition comprising an analgesic agent substantially free or of its R(-) antipode selected from the group consisting of (S+)-ibuprofen, (S+) flurbiprofen and (S+) ketoprofen, pharmaceutically-acceptable salts thereof, and mixtures thereof along with at least one of (a) a decongestant, (b) an expectorant and (c) an antitussive. BACKGROUND OF THE INVENTION

The common coϊd, although not usually a serious illness, is a highly prevalent, discomforting and annoying infliction. The term "common cold" is applied to minor respiratory illnesses caused by a variety of different respiratory viruses. While rhinoviruses are the major known cause of common colds, accounting for approximately 30 percent of colds in adults, viruses in several other groups are also important. While immune responses occur, and infection with some respiratory tract viruses therefore could be prevented by a vaccine, development of a polytypic vaccine to cover all possible agents is impractical. Thus, the problem of controlling acute upper respiratory disease presents complex challenges, and the long-desired discovery of a single cure for the common cold is an unrealistic expectation.

Early symptoms may be minimal with only mild malaise, sore throat and nasal complaints. With rhinovirus infection, symptoms of nasal discharge, nasal congestion, and sneezing usually commence on the first day of illness and progress to maximum severity by the second or third day. Along with nasal symptoms may come sore, dry or scratchy throat and hoarseness and cough. Other symptoms may include mild burning of the eyes, loss of smell and taste, a feeling of pressure or fullness in the sinuses or ears, headache, and vocal impairment. Fever can occur, but is uncommon. Influenza infection generally includes fever, often of sudden onset and persisting for several days, and with great severity; generalized aches and pains; fatigue an weakness; and chest discomfort.

At present, only symptomatic treatment is available for th common cold. The costs of treating colds with over-the-counte medications in the United States is estimated at an annual cost o over 1.5 billion dollars. The direct costs of treatment in outpatien clinics is estimated at almost four billion dollars. Indirect costs, based on the amount of loss in wages because of restricted activit are substantially higher. Exemplary prior art formulations for treatment of cough, cold, cold-like and/or flu symptoms and the discomfort, pain, fever an general malaise associated therewith generally contain an analgesi (aspirin or acetaminophen) and one or more antihistaminics, decon gestants, cough suppressants, antitussives and expectorants. The use of non-steroidal anti-inflammatory drugs to comba inflammation and attendant pain is accepted medical practice. Th non-steroidals are commonly employed to relieve pain and inflammatio associated with, for example, bursitis, arthritis, headache and th like. Among the most commonly used drugs of the non-narcotic anal- gesic class of drugs are aspirin, acetaminophen, ibuprofen and naprox- en. Aspirin, acetaminophen and ibuprofen have heretofore been includ¬ ed as the pain reliever and fever-reducing component in conventional cough/cold multi-symptom alleviating compositions. These commerciall marketed products generally contain in addition to aspirin, acetamino- phen or ibuprofen, one or more antihistaminics, decongestants, cough- suppressants, antitussives and expectorants.

Ibuprofen, or (+) 2-(p-isobutylphenyl)propionic acid, is well-known as a nonsteroidal anti-inflammatory drug having analgesic and antipyretic activity. Ibuprofen is currently marketed b prescription in the United States generically, as well as unde tradenames such as Motrin^®, which is available in 400, 600 and 800 mg tablets for oral administration. Ibuprofen has recently also become available in this country in non-prescription strength (200 mg) under a variety of tradenames, including Advil^® and Nuprin^®, as well as in generic form. For the treatment of mild to moderate pain, 400 mg every 4 to 6 hours, not to exceed 3200 mg daily, is generally recommended for Motrin®. The lower dose over-the-counter products are generally recommended for minor aches and pains, to be used orally at the 200 to 400 mg level, every 4 to 6 hours, not to exceed 1200 m daily unless directed by a physician.

Flurbiprofen, or (+) [l,l'-biphenyl]-4-acetic acid 2-fluoro-alphamethyl, is also well-known as a nonsteroida anti-inflammatory drug having analgesic and antipyretic activity Flurbiprofen is currently marketed by prescription in the Unite States under the tradename Ansaid^®, which is available in 50 and 10 mg tablets for oral administration.

Ketoprofen, or (+) 2-(3-benzoylphenyl)propionic acid, anothe well-known nonsteroidal anti-inflammatory drug having analgesic an antipyretic activity is currently marketed by prescription in th United States under the tradename Orudis®, which is available in 25 50 and 75 mg capsules for oral administration. For the treatment o mild to moderate pain, 25-50 mg every 6 to 8 hours, not to exceed 30 mg daily, is generally recommended for Orudis^®. See Physician 's Des Reference, 46th edition, 1992, publisher Edward R. Barnhart, Medica Economics Company, Inc., Oradell, N.J. 07649, pp. 2351-54, 2319-20 an 2488-90, the disclosure of which is incorporated herein.

As apparent from their chemical nomenclature, these analgesi agents are racemic mixtures. It is only the racemic mixture of thes agents which have in fact ever been marketed. There have, however been some studies of the individual S(+) and R(-) enantiomer o ibuprofen. In the body, some of the R(-) enantiomer is converted t the S(+) enantiomer, which is the pharmaceutically active form o ibuprofen.

The use of the racemic mixture of ibuprofen together wit caffeine has been disclosed in, for example, in U.S. Patent 4,464,37 to Sunshine et al . issued August, 7, 1984. The use of ibuprofen, a well as other of the newer non-steroidal anti-inflammatory agent (i.e., excluding aspirin, acetaminophen and phenacetin) in th preparation of cough/cold pharmaceutical compositions containing amines, has been disclosed in, for example, U.S Patent 4,552,899 to Sunshine et al . issued November 12, 1985.

The use of naproxen as well as other of the newer non-steroida anti-inflammatory agents (i.e., excluding aspirin, acetaminophen an phenacetin) in the preparation of cough/cold pharmaceutical composi tions has been disclosed in, for example, U.S. Patent 4,552,899 t Sunshine et al . issued November 12, 1985. The use of some of thes newer NSAID's alone to treat upper respiratory infections has been disclosed in "Therapeutic Utility of Naproxen in Acute Upper Respira¬ tory Infection -- Multiclinical Double Blind Study" Kansenshoqaku Zasshi 52 (5):148-163 (1978), "Clinical Evaluation of Sulindac (Clino- ril®) in the Treatment of Acute Upper Respiratory Tract Inflammation -- Double Blind Comparison With Ibuprofen", Kansenshoqaku Zasshi. Vol. 57, No. 3, pp. 260-272 (1983); "Double Blind Controlled Study of Miroprofen in Acute Upper Respiratory Tract Infections. Comparison with Ibuprofen" Kansenshoqaku Zasshi. Vol. 50, No. 5, pp. 435-453, 1982, "Therapeutic Effects of Fenbufen on the Common Cold. Multi- clinic Double-Blind Study" Kansenshoqaku Zasshi. Vol. 51, No. 4, pp. 184-196, (1977); "Clinical Evaluation of Clinoril Tablets in Acute Respiratory Tract Infections", Kansenshoqaku Zasshi. Vol. 56, No. 12, pp. 1186-1195, 1982. The use of the S(+) form of ibuprofen has been disclosed in, for example, U.S. Patent 4,851,444 to Sunshine et al. issued July 25, 1989 and in combination with antihista ines in WO 9,205,783 to Gates et al. published April 16, 1992.

The present inventors have found that selected compositions comprising an analgesic agent substantially free of its R(-) antipode selected from the group consisting of (S+)-ibuprofen, (S+) flurbiprofen and (S+) ketoprofen, pharmaceutically-acceptable salts thereof and mixtures thereof, with at least one of (a) a decongestant, (b) an expectorant and (c) an antitussive provides improved treatment, management or mitigation of cold, cold-like and/or flu symptoms.

It is therefore an object of the present invention to provide a method for the treatment of cough, cold, cold-like and/or flu symptoms in a mammalian organism in need of such treatment comprising adminis¬ tering to such organism the compositions of the present invention. Such symptoms as used herein refer to coryza, nasal congestion, sinus congestion, sinus pain, upper respiratory infections, allergic rhinitis, otitis, sinitis, etc.

SUMMARY OF THE INVENTION The present invention relates to compositions and methods for providing improved treatment, management or mitigation of cold, cold-like and/or flu symptoms by administering a safe and effective amount of a composition comprising an analgesic agent substantially free or of its R(-) antipode selected from the group consisting of (S+)-ibuprofen, (S+) flurbiprofen and (S+) ketoprofen, pharmaceutically-acceptable salts thereof, and mixtures thereof along with at least one of (a) a decongestant, (b) an expectorant and (c) an antitussive. All percentages and ratios used herein are by weight unless otherwise indicated.

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to compositions and methods for providing improved treatment, management or mitigation of cold, cold-like and/or flu symptoms by administering a safe and effective amount of a composition comprising an analgesic agent substantially free or of its R(-) antipode selected from the group consisting of (S+)-ibuprofen, (S+) flurbiprofen and (S+) ketoprofen, pharmaceutically-acceptable salts thereof, and mixtures thereof along with at least one of (a) a decongestant, (b) an expectorant and (c) an antitussive.

The term "S(+)" as applied to the analgesic agents herein is intended to encompass not only the dextrorotatory or S(+) iso er of these agents but also any pharmaceutically acceptable, analgesically effective salt thereof. The expression "substantially free of the R(-) antipode" as used in conjunction with the term "S(+)" means that the S(+) enantiomer is sufficiently free it is R(-) antipode to exert the desired onset-hastened and enhanced analgesic effect. Practically speaking, this means that the active ingredient should contain at least 90% by weight of the S(+) enantiomer and 10% or less weight R(-) enantiomer. Preferably, the weight ratio of S(+) enantiomer to R(-) enantiomer is greater than 20:1, more preferably greater than 97:3. Most preferably the S(+) enantiomer is 99 or more % by weight free of R(-) enantiomer, i.e., the weight ratio of S to R is approximately equal to or greater than 99:1.

The safe and effective amount of S(+) ibuprofen used in the compositions of the present invention generally ranges from about 50 to about 800 mg, preferably from about 50 to about 400 mg, more preferably from about 50 to about 200 mg and most preferably from about 50 to about 100 mg. The safe and effective amount of S(+) flurbiprofen used in the compositions of the present invention generally ranges from about 12.5 to about 300 mg, preferably from about 12.5 to about 200 mg, more preferably from about 12.5 to about 100 mg and most preferably from about 12.5 to about 50 mg. The safe and effective amount of S(+) ketoprofen used in the compositions of the present invention generally ranges from about 5 to about 100 mg, preferably from about 5 to about 75 mg, more preferably from about 5 to about 50 mg and most preferably from about 5 to about 25 mg.

The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic bases including inorganic bases and organic bases. Salts derived from nonorganic bases include sodium, potassium, lithium, ammonia, calcium, magnesium, ferrous, zinc, manganous, aluminum, ferric, manganic salts and the like. Salts derived from pharmaceutically acceptable organic non- toxic bases include salts of primary, secondary, tertiary and quater¬ nary amines, substituted amines including naturally occurring substi¬ tuted amines, cyclic amines and basic ion exchange resins, such as triethylamine, tripropylamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, lysine, arginine, histidine, caffeine, procaine, N-ethylpiperidine, hydraba ine, choline, betaine, ethylenediamine, glucosa ine, methylglycamine, theobromine, purines, piperazine, piperidine, polyamine resins and the like. The compositions of the present invention also include at least one other pharmacological active selected from the following class: (a) a decongestant, (b) an expectorant and (c) an antitussive. The decongestants useful in the compositions of the present invention include pseudoephedrine, phenylpropanolamine, phenylephrine and ephe- drine, their pharmaceutically acceptable salts, and mixtures thereof. The antitussives useful in the present invention include those such as dextromethorphan, chlophedianol, carbetapentane, caramiphen, noscapine, diphenhydramine, codeine, hydrocodone, hydromorphone, fominoben, their pharmaceutically-acceptable salts, and mixtures thereof. The expectorants (also known as mucolytic agents) useful in the present invention include glyceryl guaiacolate, terpin hydrate, ammonium chloride, N-acetylcysteine and bromhexine, ambroxol, their pharmaceutically acceptable salts, and mixtures thereof. All of these components, as well as their acceptable dosage ranges are described in the following: U.S. Patent 4,783,465 to Sunshine et al., issued November 8, 1988, U.S. Patent 4,619,934 to Sunshine et al., issued October 28, 1986, which are incorporated by reference herein. Preferably, the pharmaceutical compositions of the present invention comprise the S(+) enantiomer and other pharmacological active in a ratio of S(+) enantiomer:pharmacological active of from about 200:1 to about 1:1, preferably from about 50:1 to about 1:1 and most preferably from about 10:1 to about 1:1.

Various oral dosage forms can be used, including such solid forms as tablets, capsules, granules, lozenges and bulk powders and liquid forms such as syrups and suspensions. These oral forms comprise a safe and effective amount, usually at least about 5% of the active component. Solid oral dosage forms preferably contain from about 5% to about 95%, more preferably from about 10% to about 95%, and most preferably from about 25% to about 95% of the active component. Liquid oral dosage forms preferably contain from about 1% to about 50% and more preferably from about 1% to about 25% and most preferably from about 3% to about 10% of the active component.

Tablets can be compressed, triturated, enteric-coated, sugar- coated, film-coated or multiple compressed, containing suitable binders, lubricants, diluents, disintegrating agents, coloring agents, flavoring agents, preservatives and flow-inducing agents. Also useful are soft gelatin capsules.

Liquid oral dosage forms include aqueous and nonaqueous solu¬ tions, emulsions, pseudo emulsions, suspensions, and solutions and/or suspensions reconstituted from non-effervescent granules, containing suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweeteners, taste-masking agents, coloring agents, and flavoring agents. Specific examples of pharmaceutically accept¬ able carriers and excipients that may be used to formulate oral dosage forms, are described in U.S. Patent 3,903,297, Robert, issued Sep¬ tember 2, 1975, incorporated by reference herein. Techniques and compositions for making solid oral dosage forms are described in Marshall, "Solid Oral Dosage Forms," Modern Pharmaceutics. Vol. 7. (Banker and Rhodes, editors), 359-427 (1979), incorporated by refer¬ ence herein. Techniques and compositions for making tablets (compressed and molded), capsules (hard and soft gelatin) and pills are described in Remington's Pharmaceutical Sciences (Arthur Osol , editor), 1553-1593 (1980), incorporated herein by reference.

In preparing the liquid oral dosage forms, the active component is incorporated into an aqueous-based orally acceptable pharmaceutical carrier consistent with conventional pharmaceutical practices. An "aqueous-based orally acceptable pharmaceutical carrier" is one wherein the entire or predominant solvent content is water. Typical carriers include simple aqueous solutions, syrups, dispersions and suspensions, and aqueous based emulsions such as the oil-in-water type. The most preferred carrier is a suspension of the pharmaceuti¬ cal composition in an aqueous vehicle containing a suitable suspending agent. Suitable suspending agents include Avicel RC-591 (a microcrys- talline cellulose/sodium carboxymethyl cellulose mixture available from FMC), guar gum and the like. Such suspending agents are well known to those skilled in the art. While the amount of water in the compositions of this invention can vary over quite a wide range depending upon the total weight and volume of the active component and other optional non-active ingredients, the total water content, based on the weight of the final composition, will generally range from about 20 to about 75%, and, preferably, from about 20 to about 40%, by weight/volume.

Although water itself may make up the entire carrier, typical liquid formulations preferably contain a co-solvent, for example, propylene glycol, glycerin, sorbitol solution and the like, to assist solubilization and incorporation of water-insoluble ingredients, such as flavoring oils and the like into the composition. In general, therefore, the compositions of this invention preferably contain from about 5 to about 25 volume/volume percent and, most preferably, from about 10 to about 20 volume/ volume percent, of the co-solvent.

The compositions of this invention may optionally contain one or more other known therapeutic agents, particularly those commonly utilized in cough/cold preparations, such as, for example, an antihistamine such as chlorpheniramine, brompheniramine, dexchlorphen- iramine, dexbromphreniramine, triprolidine, azatadine, doxylamine, tripelennamine, cyproheptadine, hydroxyzine, clemastine, carbinox- amine, phenindamine, bromodiphenhydramine, pyrila ine, their pharmaceutically acceptable salts, as well as the non-sedating anti- histamines which include acrivastine, AHR-11325, astemizole, azelas- tine, cetirizine, ebastine, ketotifen, lodoxamide, loratidine, levoca- bastine, mequitazine, oxato ide, setastine, tazifylline, temelastine, and terfenadine, their pharmaceutically acceptable salts: all of these components, as well as their acceptable dosage ranges are described in the following: U.S. Patent 4,783,465 to Sunshine et al. issued November 8, 1988, U.S. Patent 4,619,934 to Sunshine et al . issued October 28, 1986, which are incorporated by reference herein Also useful are bronchodilators such as terbutaline, aminophylline epinephrine, isoprenaline, metaproterenol, bitoterol, theophylline an albuterol as well as other analgesic agents such as acetaminophen an aspirin. A highly preferred optional component is caffeine.

Other optional ingredients well known to the pharmacist's art ma also be included in amounts generally known for these ingredients, fo example, natural or artificial sweeteners, flavoring agents, colorant and the like to provide a palatable and pleasant looking final prod uct, antioxidants, for example, butylated hydroxy anisole or butylate hydroxy toluene, and preservatives, for example, methyl or propy paraben or sodium benzoate, to prolong and enhance shelf life. METHOD OF TREATMENT

The amount of the pharmaceutical composition administered depend upon the percent of active ingredients within its formula, which is function of the amount of the naphthalene derivative and any optiona components such as a decongestant, cough suppressant, expectoran and/or antihista ine required per dose, stability, release character istics and other pharmaceutical parameters.

Usually from about 1 mg/kg to about 50 mg/kg per day, preferabl from about 2 mg/kg to about 30 mg/kg per day and most preferably fro about 3 mg/kg per day to about 20 mg/kg per day of the pharmaceutica composition is administered as described herein. This amount can b given in a single dose, or, preferably, in multiple (two to six) dose repeatedly or sustained release dosages over the course of treatment Generally, each individual dosage of the pharmaceutical composition of the present invention range from about 1 mg/kg to about 25 mg/kg preferably from about 2 mg/kg to about 15 mg/kg and most preferabl from about 3 mg/kg to about 10 mg/kg. While dosages higher than th foregoing are effective to provide relief from cough, cold-like, fl and flu-like symptoms, care must be taken, as with any drug, in som individuals to prevent adverse side effects, The following examples illustrate embodiments of the subjec invention wherein both essential and optional ingredients are com bined. EXAMPLE I A hard gelatin capsule composition for oral administration is prepared by combining the following ingredients: Ingredient Amount S(+) Ibuprofen 100 mg

Pseudoephedrine HC1 30 mg

Triturate active ingredients and q.s. with lactose to selected capsule size.

Administration of 1 or 2 of the above capsules to a human in need of treatment provides improved relief from cough, cold-like, flu and flu-like symptoms.

EXAMPLE II A hard gelatin capsule composition for oral administration is prepared by combining the following ingredients: Ingredient Amount

S(+) Flurbiprofen 50 mg

Pseudoephedrine HC1 30 g

Astemizole 5 mg

Glyceryl guaiacolate 100 mg Triturate active ingredients and q.s. with lactose to selected capsule size.

Administration of 1 or 2 of the above capsules to a human in need of treatment provides improved relief from cough, cold-like, flu and flu-like symptoms. EXAMPLE III

A liquid composition for oral administration is prepared by ning the following iingredients:

Ingredient % W/V

S(+) Ibuprofen 1.00

Alcohol (95%) 25.000

Pseudoephedrine HC1 0.30

Propylene Glycol 25.000

Sodium Citrate 2.000

Citric Acid 0.250

Liquid Sugar (Simple J Syrup) 25.00

Glycerin 7.000

Colorants 0.008

Flavor 0.500 Water, Purified QS 100.000

The purified water (approximately 10% of the final batch volume) is poured into a batch container equipped with a lightnin' mixer. The sodium citrate, citric acid, and actives other than ibuprofen are added sequentially and dissolved with agitation. The glycerin and liquid sugar are then colorants added. In a separate container the colorants are added to purified water (approximately 0.5% of the final batch volume). This colorant solution is then added to the first batch container. In a seperate container the ibuprofen is added to the alcohol while stirring. The propylene glycol, other actives and flavors are added to this alcohol pre ix and the resulting mixture is stirred until homogeneous and then added to the first container. The remaining purified water is added to the resulting mixture and stirred. Administration of 10 ml to 20 ml (2 to 4 teaspoonsful) to a human in need of treatment provides improved relief from cough, cold-like, flu and flu-like symptoms.

EXAMPLE IV A liquid composition for oral administration is prepared by combining the following ingredients:

Ingredient % W/V

S(+) Ibuprofen 1.00

Chlorpheniramine Maleate 0.02

Pseudoephedrine HC1 0.30 Alcohol (95%) 25.00

Propylene Glycol 25.00

Sodium Citrate 2.00

Citric Acid 0.25

Liquid Sugar (Simple Syrup) 25.00 Glycerin 7.00

Colorants 0.008

Flavor 0.50

Water, Purified QS 100.00

The purified water (approximately 10% of the final batch volume) is poured into a batch container equipped with a lightnin' mixer. The sodium citrate, citric acid, pseudoephedrine HC1 and chlorpheniramine maleate are added sequentially and dissolved with agitation. The glycerin and liquid sugar are then added. In a seperate container the colorants are added to purified water (approximately 0.5% of the final batch volume). This colorant solution is then added to the first batch container. In a separate container the ibuprofen is added to the alcohol while stirring. The propylene glycol and flavors are added to this alcohol premix and the resulting mixture is stirred until homogeneous and then added to the first container. The remaining purified water is added to the resulting mixture and stirred. Administration of 10 ml to 20 ml (2 to 4 Teaspoonsful) to a human in need of treatment provides improved analgesic and/or anti-inflammatory effect.

EXAMPLE V A liquid composition for oral administration is prepared by combining the following ingredients:

Ingredient % W/V

S(+) Ibuprofen 1.00

Pseudoephedrine HC1 0.30

Chlorpheniramine Maleate 0.02 Dextromethorphan HBr 0.15

Alcohol (95%) 25.00

Propylene Glycol 25.00

Sodium Citrate 2.00

Citric Acid 0.25 Liquid Sugar (Simple Syrup) 25.00 Glycerin 7.00

Colorants 0.008

Flavor 0.50

Water, Purified QS 100.00 The purified water (approximately 10% of the final batch volume) is poured into a batch container equipped with a lightnin' mixer. The sodium citrate, citric acid, pseudoephedrine HC1 and chlorpheniramine maleate are added sequentially and dissolved with agitation. The glycerin and liquid sugar are then added. In a seperate container the colorants are added to purified water (approximately 0.5% of the final batch volume). This colorant solution is then added to the first batch container. In a separate container the ibuprofen and dextro¬ methorphan HBr are added sequentially to the alcohol while stirring. The propylene glycol and flavors are added to this alcohol premix and the resulting mixture is stirred until homogeneous and then added to the first container. The remaining purified water is added to the resulting mixture and stirred.

Administration of 10 ml to 20 ml (2 to 4 teaspoonsful) to a human in need of treatment provides improved relief from cough, cold-like, flu and flu-like symptoms.

Claims

1. A composition for providing improved treatment, management or mitigation of cold, cold-like and/or flu symptoms by administering a safe and effective amount of a composition comprising an analgesic agent substantially free or of its R(-) antipode selected from the group consisting of (S+)-ibuprofen, (S+) flurbiprofen and (S+) ketoprofen, pharmaceutically-acceptable salts thereof, and mixtures thereof along with at least one of (a) a decongestant, (b) an expectorant and (c) an antitussive.

2. A pharmaceutical composition according to Claim 1 comprising from 50 to 800 mg, preferably 50 to 400 mg and most preferably 50 to 200 mg S(+)- ibuprofen.

3. A pharmaceutical composition according to Claim 1 comprising from 12.5 to 300 mg, preferably from 12.5 to 100 mg and most preferably from 12.5 to 50 mg S(+)-flurbiprofen.

4. A pharmaceutical composition according to Claim 1 comprising from 5 to 75 mg, preferably from 5 to 50 mg and most preferably from 5 to 25 mg S(+)- ketoprofen.

5. A pharmaceutical composition according to any of the preceding Claims wherein said decongestant is pseudoephedrine, phenylpropanolamine, phenylephrine and ephedrine, mixtures thereof or pharmaceutically acceptable salts thereof.

6. A pharmaceutical composition according to any of the preceding Claims wherein said antitussive is selected from the group consisting of dextromethorphan, chlophedianol, carbetapentane, caramiphen, noscapine, diphenhydramine, codeine, hydrocodone, hydromorphone, fominoben, mixtures thereof or pharmaceutically acceptable salts thereof.

7. A pharmaceutical composition according to any of the preceding Claims wherein said expectorant is an expectorant or mucolytic such as glyceryl guaiacolate, terpin hydrate, ammonium chloride, N-acetylcysteine, bromhexine and ambroxol, mixtures thereof or pharmaceutically acceptable salts thereof.

8. A composition according to any of the preceding Claims which further comprises an antihistamine which is selected from the group consisting of chlorpheniramine, brompheniramine, dexchlorpheniramine, dexbromphreniramine, triprolidine, doxylamine, tripelennamine, cyproheptadine, carbinoxamine, bromodiphenhydramine, pyrilamine, acrivastine, AHR- 11325, phenindamine, astemizole, azatadine, azelastine, cetirizine, ebastine, ketotifen, lodoxamide, loratidine, levocabastine, mequitazine, oxatomide, setastine, tazifylline, temelastine, and terfenadine, mixtures thereof or pharmaceutically acceptable salts thereof.