MXPA00006254A - Composition for treating respiratory and skin diseases, comprising at least one leukotriene antagonist and at least one antihistamine - Google Patents

Abstract

A pharmaceutical composition useful in the treatment of sneezing, itching runny nose, nasal congestion, redness of the eye, tearing, itching of the ears or palate, shortness of breath, inflammation of the bronchial mucosa, reduced Forced Expiratory Volume In One Second (FEV1), coughs, rash, itchy skin, headaches, and aches and pains associated with seasonal allergic rhinitis, perennial allergic rhinitis, common colds, otitis, sinusitus, allergy, asthma, allergic asthma and/or inflammation, in a mammalian organism in need of such treatment. The composition comprises:i) an effective amount of at least one leukotriene antagonist selected from a) montelukast, b) 1-(((R)- (3-(2-(6,7- difluoro-2- quinolinyl)ethenyl) phenyl)-3-(2- (2-hydroxy-2- propyl)phenyl) thio)methylcyclopropaneacetic acid;c) 1-(((1(R)-3 (3-(2-(2,3- dichlorothieno[3, 2-b]pyridin-5-yl) -(E)-ethenyl)phenyl) -3-(2-(1-hydroxy-1- methylethyl) phenyl)propyl) thio)methyl) cyclopropaneacetic acid;d) pranlukast;or f) [2-[[2-(4-i(tert) -butyl-2-thiazolyl) -5-benzofuranyl]oxymethyl]phenyl]acetic acid;or a pharmaceutically acceptable salt thereof;in admixture with ii) an effective amount of at least one antihistamine which is descarboethoxyloratidine, cetirizine, fexofenadine, ebastine, astemizole, norastemizole, epinastine, efletirizine or a pharmaceutically acceptable salt thereof.

Description

COMPOSITION TO TREAT RESPIRATORY DISEASES AND OF SKIN THAT COMPRISES AT LEAST ONE ANTAGONIST LEUKOTRENE AND AT LEAST ONE ANTIHISTAMINIC BACKGROUND OF THE INVENTION The present invention relates to compositions for treating allergic rhinitis and other allergic diseases. The products of the 5-lipoxygenase pathway of arachidonic acid metabolism, particularly the leukotrienes, can mediate bronchoconstriction, mucous secretion, mucosal edema of the airways, chemotaxis and mobilization of cells in the airways in the inflammatory process of the asthma. Although they are useful, leukotriene antagonists, in and of themselves, are not able to effectively treat the multitude of symptoms that may be associated with a respiratory tract disease, such as seasonal allergic rhinitis, rhinitis permanent allergy, common colds, sinusitis and concomitant symptoms associated with allergic asthma. Symptoms of these diseases may include sneezing, runny and itchy nose, stuffy nose, red eyes, tearing, itching of the ears or palate, and cough associated with postnasal drip. It would be desirable to increase the efficacy of leukotriene antagonists to improve their overall efficacy.

BRIEF DESCRIPTION OF THE INVENTION In one embodiment, the present invention relates to a pharmaceutical composition comprising: 1) an effective amount of at least one leukotriene antagonist that is: a) a montelukast, b) 1 - (((R) - (3- (2- (6,7-difluoro-2-quinolinyl) ethenyl) phenyl) -3- (2- (2-hydroxy-2-propyl) phenyl) thio) methylcyclopropaneacetic acid c) 1 - (((1 (R)) ) -3 (3- (2- (2,3-dichlorothieno [3,2-b] pyridin-5-yl) - (E) -ethenyl) phenyl) -3- (2- (1-hydroxy-1 - methylethyl) phenyI) propyl) thio) methyl) cyclopropanoacetic; d) pranlukast; e) zafirlukast; of) [2 - [[2- (4-tert-butyl-2-thiazolyl) -5-benzofuranyl] oxymethyl] phenyl] acetic acid or a pharmaceutically acceptable salt, mixed with ii) an effective amount of at least one antihistamine which is descarboethoxyloratidine, cetirizine, fexofenadine, ebastine, astemizole, norastemizole, epinastine, efletirizine or an acceptable pharmaceutical salt. Preferably the pharmaceutical composition is designed for oral administration. Preferably, the leukotriene antagonist is montelukast and the pharmaceutically acceptable salt of the monoleukast is montelukast sodium. It is also preferred that the pharmaceutically acceptable salt of the monoleukast be about 10 milligrams (mg). More preferably, the antihistamine is descarboethoxyloratidine. Preferably, a pharmaceutically acceptable salt of cetirizine or fexofenadine is the hydrochloride salt. It is also preferred that the descarboethoxyloratadine or cetirizine have between about 2.5 and about 20 mg, more preferably between about 5, 7.5 or 10 mg. Preferably, the fexofenadine has between about 60 and about 180 mg. More preferably, the pharmaceutically acceptable salt of montelukast has between about 10 mg and the descarboethoxylocytidine has between about 5 or 7.5 mg. Optionally, the pharmaceutical composition may further comprise a third active ingredient which may be: III) a decongestant (eg, pseudoephedrine), a cough suppressant (e.g., dextromethorphan), an expectorant / mucolytic (e.g., guaifenesin) ). NSAIDs or analgesics (such as aspirin, acetaminophen, and phenacetin). The present invention is useful for treating skin diseases, the respiratory tract and / or associated concomitant symptoms, in a mammal in need of treatment, which comprises administering to said mammal a pharmaceutical composition as described above. Skin diseases include atopic dermatitis, psoriasis and chronic idiopathic urticaria, known as itchy skin and / or tingling. Respiratory tract diseases include seasonal allergic rhinitis, perennial allergic rhinitis, common colds, otitis, sinusitis, allergy, asthma, allergic asthma and / or inflammation. Symptoms associated with diseases of the respiratory tract include sneezing, itching and / or runny nose, nasal congestion; redness, runny or itchy eyes; Itching in the ears or palate, shortness of breath, inflammation of the bronchial mucosa, forced expiratory volume in one second (reduced FEV, cough, rash, tingling, itchy skin, headaches and persistent pains and pains. decarboxytoxylocytidine, cetirizine, fexofenadine, ebastine, astemizole, norastemizole, epinastine, efletirifine or its pharmaceutically acceptable salt and a leukotriene antagonist or its pharmaceutically acceptable salt can be administered either substantially together in separate or combined dosage forms in a unit dosage form as described for the above pharmaceutical composition, preferably the mammal is a human.Preferably, the separate dosage forms and the unit dosage form of the above pharmaceutical composition are designed for oral administration.Preferably, the separate dosage forms and the form of unit dose comprises between 5 and 7.5 mg of descarboethoxyloratidine and 10 mg of montelukast sodium.

DETAILED DESCRIPTION OF THE REALIZATIONS Antihistamines The descarboetoxiloratidina (DCL) is a non-sedative antihistamine whose technical name is 8-chloro-6,1-dihydro-1- (4-piperidiidene) -5H-benzo [5,6] cyclohepta [1,2] pyrid Na This compound is described in Quercia, et al., Hosp. Formul., 28: 137-53 (1993), in U.S. Patent No. 4,659,716, and in WO 96/20708. DCL is an H-1 histamine receptor protein. The H1- receptors are those that mediate the response antagonized by conventional antihistamines. H-1 receptors are present, for example, in the ileum, skin and bronchial soft muscle of man and other mammals. The amount of DCL that can be used in a unit (for example, simple) form of the present compositions can be within a range between about 2.5 and about 20 mg, also between about 5 and about 10 mg, preferably between around 5 and about 7.5 mg. Cetirizine is an antihistamine, whose name is (+) - [2- [4- (p-chloro-phenylbenzyl) -1-piperazinyl] ethoxy] acetic acid. Preferably, the pharmaceutically available salt is the hydrochloride, also known as cetirizine hydrochloride. The chemical structure of this compound is as follows: The amount of cetirizine that can be used in the unit dosage form of the present composition can be within a range between about 2.5 and 20 mg, also between about 5 and about 10 milligrams, preferably about 10 milligrams. Fexofenadine (MDL 16.455A) is a non-sedative antihistamine, whose technical name is 4- [1- (hydroxy-4- (4-hydroxy-diphenylmethyl) -1-piperidinyl) butyl] -a, -dimethyl-benzene acetic acid. . Preferably, the pharmaceutically acceptable salt is the hydrochloride, also known as fexofenadine hydrochloride. The amount of fexofenadine that can be used in a unit dose form of the present composition can be within a range between about 40 and about 200 mg, also between about 60 and about 180 milligrams, also about 120 milligrams. Ebastine is an antihistamine, whose technical name is 1- [4- (1,1-d-methylethyl) phenyl] -4- [4- (diphenylmethoxy) -1-piperidinyl-1-butanone. CAS90729-43-4. The compound is described in EP 134124. The structure for this compound is as follows: The amount of ebastine that can be used in a unit dosage form can be within a range between about 5 and about 20 mg, preferably about 10 mg.

Astemizole is an antihistamine, whose technical name is 1 - [(4-fluorophenyl) methyl] -N- [1- [2- (methoxyphenyl) ethi] -4-piperidinyl] -1H-benzamidazole-2-amine . CAS 68844-77-9. The compound is described in U.S. Patent No. 4,219,559. The chemical structure of this compound is as follows: The amount of astemizole that can be used in a unit dosage form can be within a range between about 5 and about 20 mg, preferably about 10 mg. Norastemizole is an antihistamine, whose technical name is 1 - ((4-fluorophenyl) methyl) -N-4-piperidinium-1 H-benzimidazoI-2-amine. CAS 75970-99-9. The compound is an active metabolite of astemizole. The chemical structure for this compound is as follows.

The amount of norastemizole that can be used in a unit dosage form can be within a range between about 5 and about 40 mg, also between about 10 and about 20 mg.

Epinastine is an antihistamine, whose technical name is 9,13b-dihydro-1 H-dibenz [c, fl imidazol [1, 5-a] azepin-3-amine. CAS80012-43-7. The compound is described in DE3008944 or Jpn. J. Clin. Pharmacol. Ther. 1991, 22, page 617. The chemical structure for this compound is as follows: The amount of epinastine that can be used in a unit dosage form can be within a range between about 1 and about 20 mg, preferably between about 2 and about 18 mg. Efletrizin (UCB-28754) is an antihistamine, whose technical name is [2- [4- [Bis (p-fluorophenyl) methyl] -1-piperazinyl] ethoxy] acetic acid. CAS 140756-35-7. The chemical structure for this compound is as follows: The amount of efletirizine that can be used in a unit dosage form can be within a range between about 4 and about 60 mg.

Leukotriene Antagonist In addition to and / or in place of the quoted amounts for any particular compound, the amount of the leukotriene antagonist that can be used in the unit dose form can be within a range between about 5 and about 500 milligrams, also between about 50 and about 300 milligrams, also between about 100 and about 200 milligrams. Montelukast is a leukotriene D4 antagonist capable of antagonizing the receptors for cysteinyl leukotrienes. The technical name of montelukast is acid [R- (E)] - 1 - [[[1- [3- [2- (7-chloro-2-quinoyl) ethenyl] phenyl] -3- [2- (1 - hydroxy-1-methylethyl) phenyI] propyl] thio] methyl] cyclopropanoacetic acid. This compound is described in EP 480,717. A pharmaceutically acceptable salt of montelukast is the monosodium salt, also known as montelukast sodium. The amount of montelukast that can be used in a unit dose form of the present invention may be within about one to 100 milligrams, also between about 5 and about 20 milligrams, preferably about 10 milligrams. The compound is 1 - (((R) - (3- (2- (6,7-difiuoro-2-quinolinyl) ethenyl) phenyl) -3- (2- (2-hydroxy-2-propyl)) phenyl) thio) methy1cyclopropaneacetic is a leukotriene antagonist described in WO 97/28797 and U.S. Patent No. 5,270,324 A pharmaceutically acceptable salt of this compound is the sodium salt, also known as 1 - (((R) - ( 3- (2- (6,7-difluoro-2-quinyl) ethenyl) phenyl) -3- (2- (2-hydroxy-2-propyl) phenyl) thio) methylcyclopropanoacetate. The compound 1 - (((1 (R) -3 (3- (2- (2,3-dichlorothieno [3,2-b] pyridin-5-yl) - (E) -ethenyl) phenyl] ) -3- (2- (1-hydroxy-1-methylethyl) phenyl) propyl) thio) methyl) cyclopropanoacetic acid is a leukotriene antagonist described in WO 97/28787 and U.S. Patent No. 5,472,964 A pharmaceutically acceptable salt of this compound is the sodium salt, also known as sodium 1 - (((1 (R) -3 (3- (2- (2,3-dichlorothieno [3,2-b] pyridin-5-yl) ) - (E) -etenyl) phenyl) -3- (2- (1-hydroxy-1-methylethyl) phenyl) propyl) thio) methyl) cyclopropanoacetate. ukast is a leukotriene antagonist described in WO 97/28797 and EP173,516. The technical name for this compound is N- [4-oxo-2- (1 H-tetrazol-5-yl) -4H-1-benzopyran-8-yl] -p- (4-phenylbutoxy) benzamide. The amount of pranlukast that can be used in a unit dosage form can be within a range between about 100 and about 700 mg, preferably between about 12 and about 675 mg; also between about 255 mg and about 450 mg; also between about 225 and about 300 mg. Zafirlukast is a leukotriene antagonist described in WO 97/28797 and EP199,543. The technical name for this compound is cyclopentyl-3- [2-methoxy-4 - [(o-tolylsulfonyl) carbamoyl] benzyl] -1-metillindole-5-carbamate. The compound [2 - [[2- (4-tert-butyl-2-thiazolyl) -5-benzofuranyl] oxymethyl] phenyl] acetic acid is a leukotriene antagonist and / or inhibitor whose method for preparing it is described in the patent No. 5,296,495 and Japanese Patent JP08325265A. An alternative name for this compound is 2 - [[[2- [4- (1,1-dimethylethyl) -2-thiazolyl] -5-benzofuranyl] oxy] methyl] -benzeneacetic acid. The code number for this compound is FK01 1 or FR150011. The compound has the molecular formula of C 24 H 23 NO 4 S and a molecular weight of 421.52. The chemical structure for this compound is as follows.

The pharmaceutical compositions of the present invention can be administered according to the age, sex, weight and severity of the condition of the patient to be treated. Generally, the human oral dosage form, which contains the descarboethoxyloratidine, cetirizine, fexofenadine, ebastine, astemizole, norastemizole, epinastine, efletirizine or its pharmaceutically acceptable salt and the leukotriene antagonist can be administered 1 or 2 times per day. The following table determines the preferred combinations of a leukotriene and antihistamine antagonist.

Leukotriene antagonist + antihistaminic Montelukast + descarboetoxiloratidina Pranlukast + descarboetoxiloratidina Montelukast + cetirizine Pranlukast + cetirizine Montelukast + Fexofenadine Pranlukast + Fexofenadine Montelukast + Ebastine Pranlukast + Ebastine Montelukast + Norastemizole Pranlukast + Norastemizole Montelukast + efletirizine Pranlukast + efletirizine The term "NSAID" as used herein It is intended to refer to any non-narcotic non-steroidal anti-inflammatory analgesic compound, including its pharmaceutically acceptable salts, which fall into one of five structural classes but excluding aspirin, acetaminophen and phenacetin, as follows: 1) Derivatives of propionic acid such as, for example, ibuprofen, naproxen, flurbiprofen, fenoprofen, ketoprofen, fenbufen and fluprofen; 2) Acetic acid derivatives such as, for example, tolmethyl sodium sulindac and indomethacin; 3) Fenamic acid derivatives such as, for example, mefanamic acid and sodium meclofenamate; 4) Biphenylcarboxylic acid derivatives, such as, for example, diflunisal or flufenisal; 5) Oxicams such as, for example, piroxicam, sudoxicam and isoxicam. Analgesics are drugs or compounds that relieve pain, including aspirin, acetaminophen, and phenacetin. In the pharmaceutical compositions and methods of the present invention, the above active ingredients will typically be administered in admixture with suitable diluents, excipients or pharmaceutical carriers (collectively referred to herein as carrier materials) suitably selected with respect to the intended form of administration, for example , oral tablets, capsules (both filled-solid, filled semi-solid or liquid filled), powders for their constitution, oral gels, elixirs, syrups, suspensions, solutions, nasal sprays, eye drops, oral drops, topical creams and the like, and they are related to conventional pharmaceutical practices. For example, for oral administration in the form of tablets or capsules, the active drug component can be combined with any non-toxic, pharmaceutically acceptable inert carrier, such as, for example, lactose, starch, sucrose, cellulose, magnesium stearate, phosphate dicalcium, calcium sulfate, mannitol, ethyl alcohol (liquid forms) and the like. Moreover, when desired or needed, suitable binders, lubricants, disintegrating agents and coloring agents can also be incorporated in the mixture. Suitable binders include starch, gelatin, natural sugars, corn sweeteners, natural and synthetic gums such as acacia, sodium alginate, carboxymethyl cellulose, polyethylene glycol and waxes. Among the lubricants there may be mentioned for use in these dosage forms boric acid, sodium benzoate, sodium acetate, sodium chloride and the like. Disintegrants include starch, methylcellulose, guar gum and the like. Sweetening and flavoring agents and preservatives can also be included when convenient. Additionally, the compositions of the present invention can be formulated in sustained release form to provide controlled release of any one or more of the components or active ingredients to optimize the therapeutic effects, for example, leukotriene antagonism, antihistaminic effect and the like. Suitable dosage forms for sustained release include layered tablets containing layers of polymer matrices of rate of disintegration or controlled release impregnated with the active components and formed in tablet or capsule form containing these impregnated porous polymer matrices or encapsulated Dosage form: composition of descarboethoxyloratidine, cetirizine, fexofenadine, ebastine, astemizole, norastemizole, epinastine, efletirizine or its pharmaceutically acceptable salt and the leukotriene antagonist formulated in a distribution system, for example, tablet, capsule, oral gel, powder for constitution or suspension in association with the inactive members. Capsule: refers to a special container or container prepared with methylcellulose, polyvinyl alcohols, or gelatins or denatured starch to support or contain compositions comprising descarboethoxyloratidine, cetirizine or fexofenadine and a leukotriene antagonist. Hard shell capsules are typically prepared from mixtures of relatively high strength bone gelatins and porcine skin gelatins. The capsule itself may contain small amounts of dyes, opacifying agents, plasticizers and preservatives. Tablet: refers to a compressed or molded solid dosage form containing the active ingredients (descarboethoxyloratidine); cetirizine or fexofenadine and leukotriene antagonist) with the appropriate diluents. The tablet can be prepared by compressing mixtures or granulations obtained by means of wet granulation, dry granulation or by means of compaction. Oral gels: refers to the descarboethoxyloratidine, cetirizine or fexofenadine and leukotriene antagonist dispersed or solubilized in a semi-solid hydrophilic matrix. Powders for constitution refer to mixtures of powders containing descarboethoxyloratidine, cetirizine or fexofenadine and a leukotriene antagonist and suitable diluents can be suspended in water or juice.

Diluent: refers to substances that generally constitute the main portion of the composition or dosage form. Suitable diluents include sugars such as, for example, lactose sucrose, mannitol and sorbitol; starches derived from wheat, corn and potato rice; and cellulose such as, for example, microcrystalline cellulose. The amount of diluent in the composition may be within a range between about 10 and about 90% by weight of the total composition, preferably between about 25 and about 75%, more preferably between about 30% and about 60% by weight, even more preferably between about 12 and about 60%. Disintegrants: refers to the materials added to the composition to help break (disintegrate) and release medications. Suitable disintegrants include starches; Modified starches "soluble in cold water" such as, for example, sodium carbiximethyl starch; natural and synthetic gums such as, for example, locust bean gum, karaya gum, guar gum, tragacanth gum and agar; cellulose derivatives such as, for example, methylcellulose and sodium carboxymethylcellulose; microcrystalline cellulose and cross-linked microcrystalline cellulose such as, for example, croscarmellose sodium; alginates such as, for example, alginic acid and sodium alginate; clays such as bentonites; and effervescent mixtures. The amount of the disintegrant in the composition can be within a range between about 2 and about 15% by weight of the composition, more preferably between about 4 and about 10% by weight. Binders: refers to the substances that agglutinate or "stick" the powders and turn them cohesive to form granules, thus serving as "adhesive" in the formulation. The binders add cohesive strength already available in the diluent or volumetric agent. Available binders include sugars such as sucrose; starches derived from wheat, corn and potato rice; natural gums such as acacia, gelatin and tragacanth; marine algae derivatives such as, for example, alginic acid, sodium alginate and calcium and ammonium alginate; cellulosic materials such as, for example, methylcellulose and sodium carboxymethylcellulose and hydroxypropylmethylcellulose; polyvinyl pyrrolidone; and inorganic, such as, for example, magnesium aluminum silicate. The amount of binder in the composition can be within a range between about 2 and about 20% by weight of the composition, more preferably between about 3 and about 10% by weight, even more preferably between about 3 and about 6% by weight. Lubricant: refers to a substance added to the dosage form to allow the tablet, granules, etc. After being compressed, it is released from the mold or matrix reducing friction or wear. Suitable lubricants include metal stearates such as, for example, magnesium stearate, calcium stearate, or potassium stearate; stearic acid; waxes of high melting point; and water-soluble lubricants such as, for example, sodium chloride, sodium benzoate, sodium acetate, sodium oleate, polyethylene glycols and d'l-leucine. Lubricants are usually added in the last step of the compression, since they must be present on the surfaces of the granules and between them and the parts of the dam for tablets. The amount of lubricant in the composition may be within a range between about 0.2 and about 5% by weight of the composition, preferably between about 0.5 and about 2%, more preferably between about 0.3 and about 1.5% in weigh. Sliding: are materials that prevent lumps from forming and improve the fluid characteristics of the granulations, in such a way that the fluid is smooth and uniform. Suitable glidants include silica dioxide and talc. The amount of glidant in the composition may be within a range between about 0.1% and about 5% by weight of the total composition, preferably between about 0.5 and about 2% by weight. Coloring agents: are the excipients that provide coloration to the composition or dosage form. These excipients may include edible grade dyes and edible grade dyes adsorbed to a suitable adsorbent such as, for example, clay or aluminum oxide. The amount of the coloring agent may vary between about 0.1 and about 5% by weight of the composition, preferably between about 0.1 and about 1%. Bioavailability: refers to the rate and degree to which the active ingredient of the drug or The therapeutic portion is adsorbed to the systemic circulation of a dosage form administered compared to the standard or control. Conventional methods for preparing the tablets are known. These methods include dry methods such as, for example, direct compression and compression of the granulation produced by compaction, wet methods or other special procedures.

Claims (11)

NOVELTY OF THE INVENTION CLAIMS

1. - A pharmaceutical composition comprising: i) an effective amount of at least one leukotriene antagonist selected from a) montelukast, b) 1 - (((R) - (3- (2- (6,7-difluoro-2) acid -quinolinyl) ethenyl) phenyl) -2- (2- (2-hydroxy-2-propyl) phenyl) thio) methylcyclopropanoacetic acid c) 1 - (((1 (R) -3 (3- (2 - (2,3-dichlorothieno [3,2-b] pyridin-5-yl) - (E) -ethenyl) phenyl-2- (2- (1-hydroxy-1-methylethyl) phenyl) propyl) thio ) methyl) cyclopropaneacetic; d) pranlukast; or e) zafirlukast; or f) [2 - [[2- (4-tert-butyl-2-thiazolyl) -5-benzofuranyl] oxymethyl] phenyl] acetic acid; or its pharmaceutically acceptable salt; mixed with ii) an effective amount of at least one antihistamine which is descarboethoxyloratidine, cetirizine, fexofenadine, ebastine, astemizole, norastemizole, epinastine, efletirizine or its pharmaceutically acceptable salt.

2. The pharmaceutical composition of claim 1 wherein the leukotriene antagonist is a) montelukast and the antihistamine is descarboethoxyloratidine, cetirizine, fexofenadine, ebastine, noratemizole or efletirizine.

3. The pharmaceutical composition of claim 2 wherein the antihistamine is descarboethoxylocytidine.

4. The pharmaceutical composition of claim 2 wherein said montelukast has about 10 milligrams and said descarboethoxyloratidine have about 5 or 7.5 milligrams.

5. The pharmaceutical composition of claim 1 wherein the leukotriene antagonist is d) pranlukast and the antihistamine is descarboethoxyloratidine, cetirizine, fexofenadine, ebastine, norastemizole or efletirizine.

6. The pharmaceutical composition of claim 5, wherein the antihistamine is descarboethoxylocytidine.

7. The pharmaceutical composition of claim 1 or 5 further comprises a third active ingredient which can be: iii) a decongestant, a cough suppressant, an expectorant / mucolytic or an analgesic.

8. The pharmaceutical composition of claim 7 wherein the decongestant is pseudoephedrine.

9. The pharmaceutical composition of claim 7 wherein said cough suppressant is dextromethorphan.

10. The pharmaceutical composition of claim 7 wherein the expectorant / mucolytic is guaifenesin.

11. The use of the composition of any one of claims 1-10 for the manufacture of a medicament for treating skin diseases, respiratory tract and / or concomitant symptoms associated with them in a mammal.