Lozenge for treating sore throat, hoarseness and associated dry cough, and inflammatory diseases of the oral and pharyngeal cavity

Abstract

The present invention relates to a pharmaceutical formulation containing a combination of (a) at least one astringent active substance and (b) at least one mucilaginous drug and the use thereof for the prevention or treatment of inflammatory diseases of the oropharyngeal region and for the treatment of painful irritations of the mucosa in the oropharyngeal region and associated irritable cough.

Claims

1. A method for the treatment of inflammatory diseases of the oropharyngeal cavity which comprises the administration of a pharmaceutical composition in the form of a lozenge, the pharmaceutical composition comprising: at least one astringent active substance comprising alum, wherein the astringent active substance is present in an amount of no greater than 10 mg and is further present in an amount of 0.1% to 1% by weight of the pharmaceutical composition; and at least one mucilaginous drug comprising Icelandic moss, wherein the mucilaginous drug is present in an amount of 50 mg to 200 mg; wherein a ratio by weight of Icelandic moss to alum is from 15:1 to 20:1.

2. The method according to claim 1, wherein the condition to be treated includes irritable cough.

3. The method according to claim 1, wherein the condition to be treated includes difficulty in swallowing.

4. The method according to claim 1, wherein the condition to be treated includes hoarseness.

5. The method according to claim 1, wherein the condition to be treated includes pain.

6. The method according to claim 1, wherein the pharmaceutical composition, consists of (a) the at least one astringent active substance; (b) the at least one mucilaginous drug and (c) at least one further adjuvant.

7. The method according to claim 1, wherein the astringent active substance is further selected from among tannin, policresulen and silver nitrate.

8. The method according to claim 7, wherein the astringent active substance consists of alum.

Description

DESCRIPTION

(1) The term combination as used herein describes at least two active substances selected from among (a) astringent active substances and (b) mucilaginous drugs, which are present in a ratio to one another that is suitable for taking them together.

(2) The term mucilaginous drug as used herein encompasses the mucilaginous drugs, the constituents and extracts thereof. Thus, for example, the term Icelandic moss as used herein encompasses Icelandic moss, its constituents and its extracts.

(3) Mucilaginous drugs used according to the invention that have proved particularly suitable are Icelandic moss (Lichen islandicus), common mallow (Malva sylvestris), lance leaf plantain (Plantago lanceolata), marshmallow (Althaea officinalis) and coltsfoot (Tussilago farfara) and the mixtures thereof. Preferably, Icelandic moss is used, particularly in the form of an extract.

(4) The term astringent active substance as used herein comprises active substances which have a drying, haemostatic and anti-inflammatory activity when they come into contact with the skin or mucosa as a result of protein precipitation. In particular, alum, tannin, policresulen and silver nitrate or mixtures thereof are suitable as astringent active substances. Preferably, alum is used.

(5) One particular embodiment of the present invention relates to a pharmaceutical formulation according to one of the preceding claims comprising (a) at least one astringent active substance; (b) at least one mucilaginous drug and (c) at least one other adjuvant.

(6) The term pharmaceutical formulation as used herein comprises in particular conventional solid pharmaceutical formulations such as lozenges, prepared for example by powder compression or based on hard caramels.

(7) Suitable adjuvants are in particular tabletting excipients and fillers, for example isomalt, fructose and/or glucose syrup, silicon dioxide, talc, magnesium stearate, macrogol, polydextrose or xanthan gum, sweeteners, for example sugar substitutes, particularly isomalt, sorbitol, polydextrose, maltitol or isomaltitol, sweeteners, for example aspartame, acesulfame, cyclamate, saccharin or xylitol, flavourings, colourings and/or stabilisers, for example tartaric acid or citric acid.

(8) The proportion by weight of the adjuvants used is normally in the range from 50 to 99.5% by weight, preferably from 75 to 99% by weight, particularly preferably from 85 to 95% by weight, based in each case on the total weight of the pharmaceutical formulation.

(9) In a particular embodiment of the pharmaceutical formulation according to the invention, Icelandic moss is used as the mucilaginous drug. Icelandic moss is preferably used as an extract.

(10) Suitable extracts of Icelandic moss are obtained for example by aqueous, alcoholic or aqueous-alcoholic extraction and optionally subsequent drying. These extracts normally consist primarily of the mucilage-forming polysaccharides lichenin and isolichenin. The increased content of mucilages improves the therapeutic effect compared with the pure drug. Besides the mucilages the extract contains lichen acids which have a slight antimicrobial effect. Compared with the drug, the processing of the extracts is easier.

(11) In one particular embodiment of the pharmaceutical formulation according to the invention, mallow is used as the mucilaginous drug. Mallow is preferably used here as an extract.

(12) Suitable extracts of mallow are obtained for example by aqueous, alcoholic or aqueous-alcoholic extraction and optionally subsequent drying. These extracts usually consist mainly of mucilages. The latter are made up of the cross-linked individual components glucose, arabinose, rhamnose and galactose. The content in the extract is many times higher than in the pure drug, thus improving the therapeutic effect.

(13) The pharmaceutical formulation according to the invention usually contains the mucilaginous drug in an amount of 1 mg to 500 mg, preferably 10 mg to 250 mg, particularly preferably 50 mg to 200 mg.

(14) The proportion by weight of the mucilaginous drug used is normally in the range from 1 to 50% by weight, preferably 2 to 25% by weight, particularly preferably 5 to 10% by weight, based in each case on the total weight of the pharmaceutical formulation.

(15) In one particular embodiment of the pharmaceutical formulation according to the invention, alum is used as the astringent active substance.

(16) In another particular embodiment of the pharmaceutical formulation according to the invention, tannin is used as the astringent active substance.

(17) The pharmaceutical formulation according to the invention normally contains the astringent active substance in an amount of 0.1 mg to 50 mg, preferably from 0.5 mg to 20 mg, particularly preferably from 1 mg to 10 mg.

(18) The proportion by weight of the astringent active substance used is normally in the range from 0.01 to 5% by weight, preferably 0.05 to 2% by weight, particularly preferably 0.1 to 1% by weight, based in each case on the total weight of the pharmaceutical formulation.

(19) A preferred embodiment of the present invention relates to the combination of Icelandic moss as mucilaginous drug and alum as astringent active substance.

(20) Icelandic moss is normally used in an amount of 1 mg to 500 mg, preferably in an amount of 10 mg to 250 mg, particularly preferably in an amount of from 50 mg to 200 mg.

(21) Alum is conventionally used in an amount of 0.1 mg to 20 mg, preferably in an amount of 1 mg to 15 mg, particularly preferably in an amount of 3 to 10 mg.

(22) The ratio by weight of Icelandic moss to alum is usually in the range from 5:1 to 50:1, preferably from 10:1 to 25:1, particularly preferably from 15:1 to 20:1.

(23) The proportion by weight of Icelandic moss and alum is usually in the range from 0.5 to 50% by weight, preferably from 1 to 25% by weight, particularly preferably from 5 to 15% by weight, based in each case on the total weight of the pharmaceutical formulation.

(24) The pharmaceutical formulation according to the invention is preferably prepared as a lozenge. Suitable lozenges may be produced for example by powder compression or based on hard caramels.

(25) The total weight of the pharmaceutical formulation is conventionally in the range from 500 mg to 5000 mg, preferably from 750 mg to 4000 mg, particularly preferably from 1000 mg to 3000 mg.

(26) The pharmaceutical formulation according to the invention is usually administered up to 20 times a day, preferably up to 12 times, particularly preferably up to 8 times a day.

(27) The combination according to the invention is suitable for the prevention or treatment of inflammatory diseases of the oropharyngeal cavity. Accordingly, the pharmaceutical formulation according to the invention is also suitable for this use.

(28) The combination according to the invention is particularly suitable for the prevention or treatment of inflammatory diseases of the oropharyngeal cavity that are painful or accompanied by pain. Accordingly, the pharmaceutical formulation according to the invention is also suitable for this use.

(29) The combination according to the invention is particularly also suitable for the symptomatic treatment of inflammatory diseases of the oropharyngeal cavity. Accordingly, the pharmaceutical formulation according to the invention is also suitable for this use.

(30) The combination according to the invention is particularly also suitable for the treatment of inflammation and/or pain in inflammatory diseases of the oropharyngeal cavity. Accordingly, the pharmaceutical formulation according to the invention is also suitable for this use.

(31) The combination according to the invention is particularly also suitable for the treatment of irritable cough, particularly in inflammatory diseases of the oropharyngeal cavity.

(32) Accordingly, the pharmaceutical formulation according to the invention is also suitable for this use.

(33) The combination according to the invention is particularly also suitable for the treatment of difficulty in swallowing, particularly in inflammatory diseases of the oropharyngeal cavity. Accordingly, the pharmaceutical formulation according to the invention is also suitable for this use.

(34) The combination according to the invention is particularly also suitable for restoring the voice that has been affected by hoarseness and pain, particularly in inflammatory diseases of the oropharyngeal cavity. Accordingly, the pharmaceutical formulation according to the invention is also suitable for this use.

(35) The combination according to the invention is particularly suitable for the topical administration of the active substances. Accordingly, the pharmaceutical formulation according to the invention is also suitable for this use.

(36) The combination according to the invention is also particularly suitable for the treatment of painful irritations of the mucosa in the oropharyngeal cavity and associated irritable cough. Accordingly, the pharmaceutical formulation according to the invention is also suitable for this use.

(37) The combination according to the invention helps to soothe the irritated and/or inflamed oropharyngeal cavity and alleviates sore throat.

(38) The combination according to the invention helps to regenerate the mucosa in the presence of symptoms caused by colds.

(39) The combination according to the invention helps in the treatment of sore throat.

(40) The combination according to the invention helps to alleviate the symptoms of throat inflammations and irritations, such as a dry, itchy or scratchy throat.

(41) The combination according to the invention helps to protect the throat from further irritation.

(42) The combination according to the invention acts as a protective film for the irritated mucosa to prevent bacterial colonisation.

(43) The combination according to the invention soothes the oropharyngeal cavity and thus helps to break the cycle of sore throat and dry cough.

(44) The combination according to the invention helps to reduce the symptoms of dry cough and alleviates cough irritation.

(45) The combination according to the invention helps to soothe and moisten the throat and thus alleviates cough.

(46) The combination according to the invention helps with difficulties in swallowing.

(47) The combination according to the invention helps with hoarseness.

(48) Another particular subject-matter of the present invention relates to the combination of (a) at least one astringent active substance and (b) at least one mucilaginous drug for use in the prevention or treatment of inflammatory diseases of the oropharyngeal cavity.

(49) Another particular subject-matter of the present invention relates to the combination of (a) at least one astringent active substance and (b) at least one mucilaginous drug for use in the treatment of painful irritations of the mucosa in the oropharyngeal cavity and associated irritable cough.

EXAMPLES

(50) 1. Production Examples

(51) Production of pharmaceutical preparations according to the invention in the form of lozenges based on an astringent active substance in conjunction with different mucilaginous drugs.

(52) Various compositions are produced in the form of lozenges based on powder compression or based on hard caramels. For the compressed lozenges, sugar substitutes, particularly isomalt, sorbitol or polydextrose may preferably be used, for the hard sweet base fructose and/or glucose syrup may be used, as sugar-free alternative sugar substitutes, particularly sugar alcohols, preferably maltitol or isomaltitol, may be used. Variable amounts of sweeteners (e.g. aspartame, acesulfame, cyclamate, saccharin or xylitol) may be added. Other excipients and active substances are incorporated in the matrix and the lozenges are produced by the production method known per se.

(53) In the case of the compressed powder mixtures, the excipients are weighed in accordance with the recipe and mixed with the matrix. In the case of liquid excipients or active substances, these may be added by means of a further granulating step. Then powder or granules are compressed to form lozenges. The excipients or active substances may be compressed jointly or separately, as selected, in one or more layers (1-, 2- or 3-layered tablets).

(54) In the case of hard caramels the raw materials are mixed according to the recipe and mixed into the heated hard caramel base. Heat-sensitive excipients and/or active substances, particularly mucilaginous drugs, preferably Icelandic moss astringent active substances, preferably alum optionally flavourings optionally colourings optionally stabilisers, particularly tartaric acid or citric acid are added in another step shortly before the final mixing and formation of the lozenges.

(55) Using these methods, sugar-free lozenges containing different amounts of astringent active substances and mucilaginous drugs are produced, for example, as illustrated in the following Tables:

(56) TABLE-US-00001 TABLE 1 1-layer lozenge produced by powder compression with 5 mg Alum and 80 mg Icelandic moss extract Raw materials Amount per lozenge [mg] isomalt 1200 silicon dioxide 8 lemon flavouring 30 menthol 2 talc 50 macrogol 25 alum 5 Icelandic moss extract 80 (drug/extract 1:1.5-2.5) Total 1400

(57) TABLE-US-00002 TABLE 2 1-layer lozenge produced by powder compression with 1 mg tannin and 150 mg mallow extract Raw materials Amount per lozenge [mg] Polydextrose 1100 silicon dioxide 10 strawberry flavouring 30 menthol 4 magnesium stearate 25 sucralose 5 tannin 1 mallow extract (drug/extract 4:1) 150 Total 1325

(58) TABLE-US-00003 TABLE 3 2-layer lozenge produced by powder compression with 5 mg alum and 80 mg Icelandic moss extract Amount per layer Amount per layer of lozenge - of lozenge - Raw materials layer 1 [mg] layer 1 [mg] sorbitol 590 490 silicon dioxide 3 3 strawberry flavouring 15 15 eucalyptus flavouring 2 2 talc 25 25 macrogol 10 10 xanthan gum 25 alum 5 Icelandic moss extract 80 (drug/extract 1:1.5-2.5) Total 1300

(59) TABLE-US-00004 TABLE 4 Lozenge based on hard caramels containing 5 mg alum and 80 mg Icelandic moss extract Raw materials Amount per lozenge [mg] isomalt 2500 peach flavouring 15 menthol 0.5 citric acid 35 sucralose 1.5 alum 5 Icelandic moss liquid extract 80 (drug/extract 1:1.5-2.5) water 53 Total 2960

(60) 2. Examples of Use

(61) 30 patients with painful irritation of the mucosa in the oropharyngeal region and in some cases with an associated irritable cough were treated with the lozenges described in the foregoing Production Examples with no additional systemic therapy. 10 patients were treated with the preparation described in Table 4, with up to six tablets being administered over a period of three days (group A). Another 10 were treated with a standard commercial preparation with only alum (9 mg per lozenge) for three days with up to six tablets (group B). Another 10 patients were given a standard commercial monopreparation with Icelandic moss (80 mg of Icelandic moss extract per lozenge) according to a similar treatment plan (group C).

(62) Whereas all the symptoms caused by the inflammations of the oral and pharyngeal mucosa were alleviated using the formulation according to the invention, only individual complaints were alleviated with the preparations in groups B and C.

(63) With the non-novel preparation in group B, an improvement was observed in the symptoms of inflammation and pain of the mucosa. Little to no improvement was observed in group B in the symptoms of hoarseness and dry mouth and the irritable cough associated therewith.

(64) In the therapy with the non-novel preparation of group C an improvement was observed primarily in the irritable cough associated with inflammations of the oral and pharyngeal mucosa, dryness of the mouth and difficulty in swallowing.

(65) The investigations demonstrate a significantly increased therapeutic success by treatment with the formulation according to the invention. Using the combination of astringent active substance and mucilaginous drug, a significant alleviation of the irritable cough as well as the symptoms of inflammation and pain took place in the patients treated with the composition according to the invention after only a short period of treatment. A rapid alleviation of the difficulty in swallowing was achieved by the application and there was a rapid restoration of voices that had been restricted by hoarseness and pain. In addition, the patients found the sucking sensation of the composition according to the invention to be very pleasant. In the improvement to the symptoms described hereinbefore, the composition according to the invention has a crucial advantage over non-novel monopreparations.