WO2020057718A1

WO2020057718A1 - New compositions comprising oregano extract and uses thereof

Info

Publication number: WO2020057718A1
Application number: PCT/EP2018/075037
Authority: WO
Inventors: Christakis Sergides; Daphne PITTA; Andreas Pittas
Original assignee: Agetis Supplements
Priority date: 2018-09-17
Filing date: 2018-09-17
Publication date: 2020-03-26
Also published as: EP3852718A1

Abstract

The present invention relates to stable compositions, such as gel compositions, comprising a gelling agent and an oregano extract. It also relates to their use as a medicament and in methods of treatment for indications including oral and dermal diseases and conditions.

Description

NEW COMPOSITIONS COMPRISING OREGANO EXTRACT

AND USES THEREOF

Field of the Invention

The present invention relates to stable compositions, such as gel compositions, comprising oregano extract. It also relates to their use as a medicament and in methods of treatment for indications including oral and dermal diseases.

Background of the Invention

Periodontal disease, commonly known as gum disease, is a group of inflammatory diseases affecting the tissues surround the teeth. Good oral hygiene is vital for avoiding gum disease. When oral hygiene is neglected, plaque containing harmful bacteria may build-up on the teeth. This may lead to the early stages of periodontal disease known as gingivitis. During gingivitis, inflammation of the gums renders the gums prone to bleeding, such as during brushing of the teeth.

If left untreated, gingivitis may progress to a more serious form of gum disease known as periodontitis. This may result in the gums pulling away from the teeth leading to teeth loosening or even falling out. Bad breath may also result.

Periodontal disease and its symptoms may be prevented and treated by killing or inhibiting the growth of the bacteria responsible.

Fungal infections of the feet arise from the growth of fungi on the skin and nails of the feet. They generally begin between the toes and move towards the soles and nails of the feet. Two common fungal infections that affect the feet are athlete’s foot and onychomycosis.

Athlete’s foot, also called tinea pedis, commonly affects athletes due to the build-up of heat and sweat in the socks and shoes that occurs during exercise. This creates an ideal environment for the growth of fungus. Athlete’s foot may cause peeling, redness, itching, burning, unpleasant odors, blisters, and sores.

Onychomycosis is a fungal infection of the nail. It may affect fingernails, but it is more common in toenails because of the moist, warm environment that may arise in the shoes and socks. Onychomycosis may cause the nails to turn grey or yellow, become hard such that they break easily, and cause unpleasant odours.

Foot fungal infections may be treated by killing or inhibiting the growth of the fungi growing on the feet.

Oregano may refer to the leaves and flowers separated from the stems of Origanum onites L. or Origanum vulgare L. subsp. Hirtum (Link) letsw. or a mixture of both species. It is a herb which has been used in traditional medicine for many years. Oregano oils, extracted from the dried leaves, are known to demonstrate antibacterial, antifungal, anti-inflammatory and/or antioxidant activity.

This activity arises from pharmaceutically active compounds present in the extract such as the major phenolic components carvacrol (2-methyl-5-(1 - methylethyl)phenol) and thymol (2-isopropyl-5-methylphenol).

Oregano and oregano extracts are therefore useful for a variety of medicinal applications in which such activity is beneficial.

However, oregano and oregano extracts readily degrade, such as by undergoing oxidation when exposed to air or light, and therefore their stability during storage may be poor making them less suitable as therapeutic compounds.

There is a need for new compositions comprising an oregano extract which are stable, such as when stored for long periods of time. Summary of the Invention According to a first embodiment, the present invention provides a composition comprising a gelling agent and an oregano extract.

According to a second embodiment, the present invention provides the composition according to the first embodiment for use as a medicament.

According to a third embodiment, the present invention provides the composition according to the first embodiment for use in the treatment of gingivitis, bleeding gums, periodontal disease, gum infections, bad breath, sensitive teeth, inflammation, tooth decay, acne, dandruff, muscle pain, or fungal infections of the nail or foot, wherein the composition is administered topically or orally.

According to a fourth embodiment, the present invention provides a method of treatment of gingivitis, bleeding gums, periodontal disease, gum infections, bad breath, sensitive teeth, inflammation, tooth decay, acne, dandruff, muscle pain, or fungal infections of the nail or foot, which comprises administering to a subject suffering such disease an effective amount of the composition according to the first embodiment, wherein the composition is administered topically or orally.

Detailed Description of the Invention

The present invention is directed to compositions comprising an oregano extract which may demonstrate excellent stability for long periods of time under typical storage conditions, and to their use as a medicament.

Preferably, the composition of the present invention is a pharmaceutical composition. The compositions of the present invention comprise an oregano extract. The oregano extract may be obtained by any method known to those skilled in the art. Preferably, the oregano extract is obtained via a solvent extraction method. For instance, the dried leaves of oregano may be processed, i.e. by cutting and crushing the leaves, and then mixed with a solvent to remove the active compounds and form the oregano extract. Any suitable solvent may be used such as water, alcohols, such as methanol, ethanol, esters, such as ethyl acetate, and methyl acetate, acetone, hydrocarbons, such as hexane, and petroleum ether, and mixtures thereof. It is preferred that the solvent is water, such as purified water which may have been filtered and/or deionised. The extraction may be carried out at any temperature such as ambient temperature, for instance from about 10°C to about 35°C, or an increased temperature, such as from about 50°C to about 200°C, preferably from about 80°C to about 150°C. The solvent extraction process may be carried out for any suitable time period, such as from about 1 minute to about 24 hours or longer, such as from about 30 minutes to about 10 hours, preferably from about 1 hour to about 6 hours.

Most preferably, the oregano extract is obtained via a process of steam distillation. The steam distillation may be carried out using a vertical condenser or a horizontal condenser. In both cases is it preferable to use a ratio of water to oregano leaves of from about 1 kg to about 50 kg of water, such as from about 5 kg to about 30 kg of water, preferably from about 10 kg to about 20 kg of water, most preferably from about 12 kg to about 15 kg of water, to about 1 kg of oregano leaves.

The skilled person will understand the range of suitable temperatures at which the steam distillation may be carried out. However, it is preferable steam distillation using a vertical condenser is carried out at a temperature of from about 100°C to about 200°C, such as from about 130°C to about 170°C, preferably from about 140°C to about 150°C. In this particular case, the steam distillation process is carried out for from about 1 minute to about 24 hours, such as from about 1 hour to about 10 hours, preferably from about 5 hours to about 6 hours. When a horizontal condenser is used, the temperature is typically from about 100°C to about 150°C, such as from about 105°C to about 120°C, preferably from about 1 10°C to about 120°C. In this particular case, the steam distillation process is carried out for from about 1 minute to about 24 hours, such as from about 30 minutes to about 5 hours, preferably from about 1 hour to about 3 hours.

As demonstrated by Example 6, it is preferable that a horizontal condenser is used for steam distillation in view of the reduced temperature requirement and lower distillation time.

The oregano extract comprises one or more compounds present in oregano leaves. The skilled person knows the types of compounds that may be extracted from oregano, and the diseases and conditions that they may be used to treat. In terms of the present invention, it is preferable that the oregano extract comprises at least one of carvacrol (2-methyl-5-(1 -methylethyl)phenol), thymol (2-isopropyl-5-methylphenol), p-cymene (1 -Methyl-4-(propan-2- yl)benzene), g-terpinene (4-Methyl-1 -(1 -methylethyl)-1 ,4-cyclohexadiene), caryophyllene ((1 R,4E,9S)-4,11 ,1 1 -Trimethyl-8 methylidenebicyclo[7.2.0]undec- 4-ene), spathulenol ((1 aR,4aR,7S,7aR,7bR)-1 ,1 ,7-Trimethyl-4-methylidene- 1 a, 2, 3, 4a, 5, 6, 7a, 7b octahydrocyclopropa[/7]azulen-7-ol), germacrene-D ((1Z,6Z)- 1 -methyl-5-methylidene-8-propan-2-ylcyclodeca-1 ,6-diene), b-fenchyl alcohol ((1 R,3R,4S)-2,2,4-trimethylbicyclo[2.2.1]heptan-3-ol), d-terpineol (2-(4- Methylidenecyclohexyl)propan-2-ol), and mixtures thereof. Most preferably, the oregano extract comprises carvacrol and thymol.

Carvacrol is typically present in the oregano extract in an amount of from about 50% to about 95% by weight, such as from about 70% to about 85% by weight, preferably from about 75% to about 80% by weight, compared to the total weight of the oregano extract.

Thymol is typically present in the oregano extract in an amount of from about 0.10% to about 2.00% by weight, such as from about 0.20% to about 1.00% by weight, preferably from about 0.40% to about 0.60% by weight, compared to the total weight of the oregano extract. The presence and amounts of such compounds in the oregano extract may be determined by any suitable analytical technique, such as gas chromatography (GC). Such techniques are as disclosed in European Pharmacopoeia 9.0 (see pages 1464 to 1466).

The oregano extract may be present in the composition of the invention in any suitable amount, such as an amount to provide a therapeutic effect. The oregano extract may be present in an amount from about 0.01 % to about 10%, preferably from about 0.1 % to about 5%, more preferably from about 0.1 % to about 3%, even more preferably from about 0.1 % to about 1 %, and most preferably from about 0.2% to about 0.6% by weight of the composition.

The composition of the present invention comprises a gelling agent. As used herein, the term“gelling agent” means a substance capable of forming a gel or acting as a thickener, for instance in the composition, thereby increasing the viscosity of the composition. Preferable viscosities are from about 3000 to about 6000 cP (centipoise), such as from about 4000 to about 5000 cP, most preferably from about 4490 to about 4500 cP. The viscosity may, however, depend upon the intended use.

The gelling agent may contribute to obtaining the required consistency of the composition, to retaining the physical characteristics of the composition, and to ensuring uniform distribution of the oregano extract in the composition.

Without wishing to be bound by theory, through the properties the gelling agent imparts on the composition, it may increase the stability of the formulation, the oregano extract, and/or one or more active compounds, such as those mentioned above, in the oregano extract. The improved stability may be with respect to oxidation in air and/or light of the compounds in the oregano extract.

Any suitable gelling agent may be used in the composition of the present invention. The gelling agent may be selected from alginic acid, sodium alginate, potassium alginate, calcium alginate, polyvinylpyrrolidone, pectin, starch, carrageenan, locust bean gum, xanthan gum, acacia gum, tragamayth, bentonite, a carbomer, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, and mixtures thereof. Preferably, the gelling agent is a type of cellulose, such as hydroxyethyl cellulose.

The gelling agent may be present in the composition in any suitable amount, such as an amount that forms a gel. The gelling agent may be present in an amount of from about 0.1 % to about 10%, more preferably from about 1 % to about 5%, and most preferably from about 2% to about 4% by weight of the composition.

A particular feature of the first aspect of the invention is that the gelling agent is hydroxyethyl cellulose which is present in an amount from about 2% to about 4% by weight of the composition.

In addition to an oregano extract and a gelling agent, the composition of the present invention may comprise one or more additional components, such as solvents, surfactants, a source of fluoride, and other pharmaceutically acceptable excipients.

The composition of the present invention may comprise one or more solvents. The solvents may be helpful in dissolving one or more components in the composition and in achieving the required consistency of the composition.

Any suitable solvent may be used in the composition of the present invention. The composition may comprise a solvent selected from propylene glycol, glycerol, water, and mixtures thereof. Preferably the composition comprises propylene glycol.

The solvent may comprise propylene glycol. When present, propylene glycol may be in the composition in an amount of from about 1 % to about 40%, more preferably from about 10% to about 30%, even more preferably from about 15% to about 25%, most preferably from about 18% to about 22% by weight of the composition. The composition may comprise glycerol. When present, glycerol may be in the composition in an amount of from about 1 % to about 40%, more preferably from about 10% to about 30%, even more preferably from about 15% to about 25%, most preferably from about 18% to about 22% by weight of the composition.

The composition may comprise water. When present, water may be in the composition in an amount of from about 30% to about 70%, more preferably from about 40% to about 60%, even more preferably from about 45% to about 55%, most preferably from about 50% to about 52% by weight of the composition.

In a particular instance, the composition comprises propylene glycol, glycerol, and water each of which may be present in the amounts defined above.

The composition of the invention may comprise a surfactant. Oregano extracts may be immiscible with water. The surfactant may help in mixing the oregano extract and water and thereby ensuring a uniform distribution of oregano extract in the composition.

Any suitable surfactant may be used in the composition of the present invention. The surfactant may be anionic, non-ionic, or cationic. They may be a non-ionic surfactant selected from polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, oleyl alcohol, and mixtures thereof. A particular feature of the first aspect of the invention is that the surfactant is selected from polysorbate 80, oleyl alcohol, or a mixture thereof.

The surfactant may be present in the composition in any suitable amount. It may be present in an amount from about 0.1 % to about 5%, preferably from about 1 % to 3% by weight of the composition.

It may be preferable that the surfactant comprises polysorbate 80, oleyl alcohol, or a mixture thereof, and present in an amount from about 1 % to about 3% by weight of the composition. A source of fluoride may be included in the composition. Fluoride may be used in order to prevent the formation of cavities in the teeth, and may therefore be particularly useful when the composition is for oral administration. The source of fluoride may be sodium fluoride. The source of fluoride, and in particular sodium fluoride, may be present in the composition in any suitable amount. It may be present in an amount of from about 0.01 % to about 1 %, preferably from about 0.1 % to about 0.5%, and most preferably from about 0.2% to about 0.3% by weight of the composition.

The composition of the present invention may comprise an analgesic or anaesthetic, such as menthol. The particular analgesic or anaesthetic used may be dependent upon the intended application of the composition. The analgesic or anaesthetic may be used to provide pain relief. The analgesic or anaesthetic, such as menthol, may be present in any suitable amount such as from about 0.01 % to about 0.1 %, preferably from about 0.02% to about 0.08%, most preferably from about 0.04% to about 0.06% by weight of the composition.

Menthol may also be included as a skin-penetration enhancer and/or to provide a cooling sensation which may occur due to its ability to dilate blood vessels. In this case, it may be present in the composition in the amounts described above in relation to the amount of analgesic or anaesthetic.

In a particularly preferred embodiment, the composition of the present invention comprises an oregano extract, hydroxyethyl cellulose, propylene glycol, glycerol, and water. Preferably, the oregano extract is present in an amount of from about 0.2% to about 0.6% by weight of the composition, hydroxyethyl cellulose is present in an amount from about 2% to about 4% by weight of the composition, propylene glycol is present in an amount from about 18% to about 22% by weight of the composition, glycerol is present in an amount from about 18% to about 22% by weight of the composition, and water is present in an amount from about 50% to about 52% by weight of the composition. The composition of the present invention may have antibacterial, antifungal, anti-inflammatory and/or antioxidant properties. Therefore, the composition of the present invention may be particularly useful as a medicament.

As a result, the composition of the present invention may be useful for the treatment of a range of diseases and conditions, for instance oral diseases and conditions, such as gingivitis, bleeding gums, periodontal disease, gum infections, bad breath, sensitive teeth, inflammation, and tooth decay, skin conditions, such as acne, and dandruff, and other diseases and conditions, such as muscle pain, and fungal infections of the nail or foot such as tinea pedis or onychomycosis.

A particularly important feature of the invention is that the composition may be suitable for topical and/or oral administration to a subject. Preferably, the subject is a mammal, and most preferably a human.

In such instances, the composition of the present invention may be administered to any area of the oral cavity, as required. Preferably, it is applied as a thin layer along both sides of the gum. The skilled person will understand the frequency that the composition may be applied to, or by, a subject, however, it is preferable that the composition is applied twice-a-day after brushing the teeth.

When the composition of the present invention is to be administered topically, it may be administered to any part of the body, as required. For instance, it may be applied as a thin layer to the foot or nail. Again, the skilled person will understand the frequency that the composition may be applied to, or by, a subject, however, it is preferable that the composition is applied twice-a- day after cleaning the affected area, such as with water and subsequent drying.

As is well known in the art, the composition of the present invention may be stored in airtight container, such as metal tubes, and kept in a cool dark place to help protect the composition against decomposing or degrading. The invention will now be described by the following, non-limiting examples. Example 1

A composition of the present invention was prepared by mixing the components listed in Table 1 as follows. First Phase: Menthol was dissolved in propylene glycol in a main tank. The mixture is visually inspected to confirm that it has dissolved.

Second Phase: Glycerin was added to the main tank and the resulting mixture was mixed for 10 minutes.

Third Phase: Polysorbate 80 was then added to the main tank. The mixture was then mixed with a homogenizer (Silverson) at a low speed for 10 minutes.

Fourth Phase: Peach flavour (liquid), caramel flavour (liquid) and oregano extract were then added to the main tank and the resulting mixture was mixed with a homogenizer (Silverson) at low speed for 15 minutes.

Fifth Phase: Acesulfame potassium and sodium fluoride were dissolved in purified water (50%) in a separate tank, and visually inspected to confirm that it was dissolved. This was then added to the main tank while it is being mixed with a homogenizer (Silverson). The remaining water was then added, and mixing was continued with a homogenizer for 15 minutes.

Sixth Phase: Flydroxyethylcellulose (Natrosol 250 M) was added to the main tank and the resulting mixture was mixed with a homogenizer (Silverson) for 5 minutes. It was then mixing for 2 hours using only baffles.

Final mixing: A vacuum was then applied to the mixture which was mixed for almost two hours. Table 1

Example 2 A composition of the present invention was prepared by mixing the components listed in Table 2 as follows.

First Phase: Menthol was dissolved in propylene glycol in a main tank. The mixture is visually inspected to confirm that it has dissolved.

Fourth Phase: Flavouring (liquid), oleyl alcohol and oregano extract were added to the main tank and the resulting mixture was mixed with a homogenizer (Silverson) at low speed for 15 minutes

Fifth Phase: Flydroxyethylcellulose (Natrosol 250 M) was dissolved in purified water (50%) in a separate tank, and visually inspected to confirm that it had dissolved without any lumps. This was then added the mixture in the main tank while it was mixed with a homogenizer (Silverson). The remaining water was then added, and mixing was continued with a homogenizer for 10 minutes.

Final mixing: A vacuum was then applied to the mixture which was mixed for almost two hours.

Table 2

Example 3 Approximately 15 g of the compositions of Example 1 and Example 2 were each subjected to stability studies under the following storage conditions:

Accelerated: 40°C ± 2°C, 75% ± 5% Relative Humidity (RH)

Long-term: 25°C ± 2°C, 60% ± 5% Relative Humidity (RH)

For the samples placed under accelerated storage conditions, the concentration of carvacrol and thymol in the composition was determined by gas chromatography (GC) at testing points of 1 month, 2 months, 3 months, and 6 months.

The concentrations (%) of carvacrol and thymol in the gel were separately determined by GC method using the formula:

P is the potency (%) of carvacrol reference standard (e.g. 99.00%) or of thymol reference standard (e.g. 99.50%). Their concentration specification limits is not less than 0.05% of thymol and carvacrol (together).

¹ Pale yellow, transparent, smooth, homogeneous gel.

² Not less than 0.05% of carvacrol and thymol.

At all testing points the concentrations were found to be within their specified concentration limits. Therefore, it may be concluded that the composition is stable following storage for up to 6 months even when stored at 40°C.

For the samples placed under long-term storage conditions, the concentration of carvacrol and thymol in the composition was determined by gas chromatography (GC) at testing points of 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, and 36 months.

The concentrations (%) of carvacrol and thymol in the gel were separately determined by GC method as mentioned above.

¹ Pale yellow, transparent, smooth, homogeneous gel.

² Not less than 0.05% of carvacrol and thymol. At all testing points the concentrations were found to be within their specified concentration limits. Therefore, it may be concluded that the composition is stable following storage for up to 36 months.

Example 4

Mouth swab samples were taken from 14 people suffering from gingivitis. The swabs were then transferred into Ringers solution. 1 ml_ of said Ringers solution was transferred to a trypticase soy agar (TSA) plate in order to create a control plate. 1 ml_ of said Ringers solution was transferred to another TSA plate along with 1 g of the composition of Example 1 in order to create a test plate. The control and test plates were incubated for five days at 30 to 35 °C.

The concentration of microorganisms on both the control plate and the test plate were then determined using a colony counter and the results are displayed in Table 3. Table 3

As may be seen from Table 3, the test plate, which included the composition of the present invention, showed a greatly reduced concentration of microorganisms compared to the control plate which did not include the composition of the invention. Therefore, it may be concluded that the composition of Example 1 demonstrates antibacterial activity against bacteria causing gingivitis. Example 5

Foot and nail swab samples were taken from 14 people suffering from a fungal infection. The swabs were then transferred into Ringers solution. 1 ml_ of said Ringers solution was transferred to a TSA plate in order to create a control plate. 1 ml_ of said Ringers solution was transferred to another TSA plate along with 1 g of the composition of Example 2 in order to create a test plate. The control and test plates were incubated for five days at 30 to 35 °C.

The concentration of microorganisms on both the control plate and the test plate were then determined using a colony counter and the results are displayed in Table 4.

Table 4

As may be seen from Table 4, the test plate, which included the composition of the present invention, showed a greatly reduced concentration of microorganisms compared to the control plate which did not include the composition of the invention. Therefore, it may be concluded that the composition of Example 2 demonstrates antifungal activity. Example 6 - formation of an oregano extract Steam distillation was performed in a 50 L reactor using either a vertical condenser or a horizontal condenser. The following examples were carried out multiple times.

(a) Vertical condenser

3.00 kg of oregano leaves were distilled with 40.00 kg of water. This means that 13.333 kg of water was used per 1 kg of oregano leaves. The distillation was performed at a temperature of about 140°C to 150°C. Under these conditions, the optimum distillation duration was 5 to 6 hours which afforded about 50-60 ml_ (45-55 g, calculated mean density of oregano oil ~0.9g/ml_) of pure oregano oil per 1 kg of oregano leaves. This is a yield of about 5 to 6% v/w or 4.5 to 5.5 % w/w.

(b) Horizontal condenser

3.00 kg of oregano leaves were distilled with 40.00 kg of water. This means that 13.33 kg of water was used per 1 kg of oregano leaves. The distillation was performed at a temperature of about 1 10°C to 120°C. Under these conditions, the optimum distillation duration was about 1 to 3 hours, and in particular about 2 hours, which afforded about 50 to 60 ml_ (45-55 g, calculated mean density of oregano oil ~0.9g/ml_) of pure oregano oil per 1 kg of oregano leaves. This is a yield of about 5 to 6% v/w or about 4.5 to 5.5% w/w.

Claims

1. A composition comprising a gelling agent and an oregano extract.

2. The composition according to claim 1 , wherein the composition is suitable for topical and/or oral administration to a subject, preferably wherein the subject is a mammal, most preferably wherein the mammal is a human.

3. The composition according to claim 1 or 2, wherein the oregano extract comprises at least one of carvacrol, thymol, p-cymene, y-terpinene, caryophyllene, spathulenol, germacrene-D, b-fenchyl alcohol, and d- terpineol, preferably the oregano extract comprises carvacrol and thymol.

4. The composition according to any preceding claim, wherein the oregano extract is present in an amount of from about 0.01 % to about 10% by weight of the composition, preferably from about 0.1 % to about 5%, more preferably from about 0.1 % to about 3 %, even more preferably from about 0.1 % to about 1 %, and most preferably from about 0.2% to about 0.6%.

5. The composition according to any preceding claim, wherein the gelling agent is selected from alginic acid, sodium alginate, potassium alginate, calcium alginate, polyvinylpyrrolidone, pectin, starch, carrageenan, locust bean gum, xanthan gum, acacia gum, tragamayth, bentonite, a carbomer, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, and mixtures thereof, preferably the gelling agent is hydroxyethyl cellulose.

6. The composition according to any preceding claim, wherein the gelling agent is present in an amount of from about 0.1 % to about 10% by weight of the composition, preferably from about 1 % to about 5%, most preferably from about 2% to about 4%.

7. The composition according to any preceding claim, wherein the composition comprises a solvent selected from propylene glycol, glycerol, water, and mixtures thereof.

8. The composition according to any preceding claim, wherein the composition comprises propylene glycol.

9. The composition according to claim 8, wherein propylene glycol is present in an amount of from about 1 % to about 40% by weight of the composition, preferably from about 10% to about 30%, preferably from about 15% to about 25%, most preferably from about 18% to about 22%.

10. The composition according to any preceding claim, wherein the composition comprises glycerol.

1 1. The composition according to claim 10, wherein glycerol is present in an amount from about 1 % to about 40% by weight of the composition, preferably from about 10% to about 30%, more preferably from about 15% to about 25%, most preferably from about 18% to about 22%.

12. The composition according to any preceding claim, wherein the composition comprises water.

13. The composition according to claim 12, wherein water is present in an amount of from about 30% to about 70% by weight of the composition, preferably from about 40% to about 60%, more preferably from about 45 % to about 55 %, most preferably from about 50% to about 52%.

14. The composition according to any preceding claim, wherein the composition comprises a surfactant.

15. The composition according to claim 14, wherein the surfactant is present in an amount of from about 0.1 % to about 5% by weight of the composition, preferably from about 1 % to about 3%.

16. The composition according to claim 14 or 15, wherein the surfactant is selected from polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, oleyl alcohol, and mixtures thereof, preferably the surfactant is selected from polysorbate 80, oleyl alcohol, and mixtures thereof.

17. The composition according to claim 1 , wherein the composition comprises hydroxyethyl cellulose, propylene glycol, glycerol, and water.

18. The composition according to claim 17, wherein hydroxyethyl cellulose is present in an amount of from about 2% to about 4% by weight of the composition, propylene glycol is present in an amount of from about 18% to about 22% by weight of the composition, glycerol is present in an amount of from about 18% to about 22% by weight of the composition, and water is present in an amount of from about 50% to about 52% by weight of the composition.

19. The composition according to any of claims 1 to 18, for use as a medicament.

20. The composition according to any of claims 1 to 18, for use in the treatment of gingivitis, bleeding gums, periodontal disease, gum infections, bad breath, sensitive teeth, inflammation, tooth decay, acne, dandruff, muscle pain, or fungal infections of the nail or foot, wherein the composition is administered topically or orally.

21. The composition for use according to claim 20, wherein the fungal infection is tinea pedis or onychomycosis.

22. A method for the treatment of gingivitis, bleeding gums, periodontal disease, gum infections, bad breath, sensitive teeth, inflammation, tooth decay, acne, dandruff, muscle pain, or fungal infections of the nail or foot, which comprises administering to a subject suffering such disease an effective amount of a composition according to any of claims 1 to 18, wherein the composition is administered topically or orally.

23. The method according to claim 22, wherein the fungal infection is tinea pedis or onychomycosis.