HK1198004A

HK1198004A - Topical formulation of ivermectin for the treatment of dermatological conditions

Info

Publication number: HK1198004A
Application number: HK14111594.1A
Authority: HK
Inventors: Manetta Vincent; R. Watkins Gary
Original assignee: Galderma S. A.
Priority date: 2003-04-24
Filing date: 2014-11-17
Publication date: 2015-03-06

Description

Topical formulation of ivermectin for the treatment of skin conditions

The present application is a divisional application of the invention patent application having application number "200480010995.4", entitled "topical formulation of ivermectin for treating skin disorders".

The present invention relates to the use of ivermectin for the production of a pharmaceutical composition for topical administration for the treatment of rosacea. It also relates to a pharmaceutical composition for topical administration comprising ivermectin for human use.

Ivermectin is two compounds belonging to the avermectins group, 5-O-demethyl-22, 23-dihydroavermectin (5-O-demethyl 1-22,23-dihydroavermectin) A_1aAnd 5-O-desmethyl-22, 23-dihydroavermectin A_1bA mixture of (a). They are also known as 22, 23-dihydroavermectins (22, 23-dihydroavermectins) B_1aAnd 22,23-dihydroavermectin B_1b. Ivermectin comprises at least 80% of 22,23-dihydroavermectin B_1aAnd less than 20% of 22,23-dihydroavermectin B_1b. This agent is part of the avermectins group of macrolides produced by the bacterium Streptomyces avermitilis (Streptomyces avermitilis) (Reynolds JEF (Ed) (1993) Martindale). Pharmacopeia supplement 29 th edition. Pharmaceutical press, london.

Ivermectin has emerged as a broad spectrum antiparasitic medicinal product for veterinary use in the mid 80's of the 20 th century (w.c. campbell, et al, (1983) ivermectin, a potential novel antiparasitic agent Science 221, 823-828). It is effective against most common intestinal worms (except tapeworms), most mites and some lice. It shows considerable affinity especially for glutamate-dependent chloride channels present in invertebrate nerve and muscle cells. Its binding to these channels can contribute to increased membrane permeability to chloride ions, which can lead to hyperpolarization of the nerve or muscle cell. And consequently neuromuscular paralysis which can lead to death of specific parasites. Ivermectin also interacts with other ligand-dependent chloride channels, including, for example, the neuromediator GABA (gamma-aminobutyric acid).

Ivermectin is more particularly an anthelmintic. This has been described in human treatment of river blindness, gastrointestinal roundworm disease (Anguillar nematosis) caused by the coccinelliasis convoluteca (Stromectol generation, and human scabies ((Meining TL et al, N Engl J Med1995Jul6i333 (1): 26-30 treatment of scabies with ivermectin), and in treatment of microfilaria in individuals diagnosed with or suspected of having lymphofilariasis due to Wuchereria Bangiae.

U.S. Pat. No. 6,133,310 discloses the topical application of ivermectin in the form of a lotion prototype comprising a mixture of ivermectin and water, and also mentions the possibility of a cream prototype comprising, in part, a mixture of ivermectin and an excipient such as propylene glycol or sodium lauryl sulfate, but does not describe such a pharmaceutical composition. These mixtures were similar to the experimental formulations used in the case of the initial results of the conceptual evidence. In fact, the elements disclosed in that patent do not give the skilled man such a teaching that an industrially useful pharmaceutical composition containing ivermectin is feasible, in particular a composition with good cosmetic properties having a sufficiently long shelf life (minimum of 2 years) for an industrial pharmaceutical product.

Despite the fact that all of these applications in humans are limited to oral administration or to the use of experimental formulations, the applicant has developed pharmaceutical compositions for topical administration comprising ivermectin for the treatment of humans. Furthermore, the applicant has surprisingly noticed that the compositions according to the invention have very good stability, especially at different pH, and good tolerance to the skin. In fact, we have found that it is particularly suitable for treating skin conditions, more particularly rosacea.

The subject of the invention is also the use of ivermectin for the production of a pharmaceutical composition for topical administration for the treatment of rosacea, a pharmaceutical composition for topical administration containing ivermectin for human use and the use of these pharmaceutical compositions for topical administration for the treatment of rosacea.

The ivermectin according to the invention comprises at least 80% of 22,23-dihydroavermectin B_1aAnd less than 20% of 22,23-dihydroavermectin B_1b。

The pharmaceutical compositions which can be used according to the invention can be used for treating the skin and can be in liquid, pasty or solid form, more particularly in the form of ointments, creams, emulsions, pomades, powders, impregnated pads, syndets, towelettes, solutions, gels, sprays, foams, suspensions, lotions, sticks, shampoos or washing bases. Or in the form of suspensions of microspheres or nanospheres for controlled release or lipid or polymeric vesicles or polymeric patches and hydrogels. The topical pharmaceutical composition may be in anhydrous form, or in aqueous form in the form of an emulsion.

In a preferred variant of the invention, the pharmaceutical composition according to the invention is in the form of an emulsion, a gel or a solution, of the cream or lotion type.

More particularly, the composition according to the invention is in the form of an emulsion.

Conventional emulsions described in the prior art are in fact unstable homogeneous systems of two immiscible liquids, one of which is dispersed in the other in the form of good droplets (micelles). This dispersion is stabilized by the action of a surfactant-emulsifier which changes the structure and the ratio of interfacial forces, thereby increasing the stability of the dispersion by reducing the interfacial tension energy.

Surfactant-emulsifiers are amphiphilic compounds having a hydrophobic part with an affinity for oil and a hydrophilic part with an affinity for water, thus creating a linkage between the two phases. So that the ionic or nonionic emulsifier can form a liquid crystal plate layer by being adsorbed on the interface to stabilize the oil/water emulsion.

The emulsifying power of nonionic surfactants is closely related to the polarity of the molecules. This polarity is defined by the HLB (hydrophilic/lipophilic balance). Conventional emulsions are generally stabilised by a mixture of surfactants, the HLB of which can vary considerably but in proportions in the mixture corresponding to the HLB required for the fatty phase to be emulsified.

The composition according to the invention will contain ingredients of this type.

The composition according to the invention is described as a stable emulsion, since it has good physical and chemical stability over time, even at temperatures above room temperature (for example 45-55 ℃), as shown in the examples described below.

Ivermectin in the composition according to the invention also surprisingly has good chemical stability upon pH change.

The compositions according to the invention advantageously contain:

a) an oil phase comprising fatty matter;

b) at least one surfactant-emulsifier;

c) ivermectin;

d) one or more solvents for the active agent and/or a pro-osmotic agent (pro-penetration agent);

e) and an emulsion of water.

More particularly, the composition according to the invention is a composition comprising:

a) an oil phase comprising fatty matter;

b) at least one surfactant-emulsifier;

c) ivermectin;

d) one or more solvents for the active agent and/or penetration enhancer

e) One or more gelling agents;

f) and an emulsion of water.

The oily phase of the compositions according to the invention may contain, for example, vegetable, mineral, animal or synthetic oils, silicone oils, Guerbet alcohols or other substances and mixtures thereof.

As examples of mineral oils, mention may be made, for example, of paraffinic oils having different viscosities, such as Primol352, Marcol82 or Marcol152 sold by the company Esso.

As vegetable oils there may be mentioned sweet almond oil, palm oil, soybean oil, sesame oil and sunflower oil.

As animal oils, mention may be made of lanolin, squalane, fish oil and mink oil.

As synthetic oils, mention may be made of esters, such as cetearyl isononanoate (cetearyl isononanoate) sold by Cognis France under the name Cetiol SN, diisopropyl adipate, such as the product of ISF under the name Ceraphyl230, isopropyl palmitate, such as the product of Croda under the name Crodamol IPP, or caprylic capric triglyceride, such as Miglyol812 sold by Huls/Lambert Rivi de.

As silicone oils, mention may be made of dimethicones such as those sold under the name Dow Corning200fluid, or cyclomethicones such as those sold under the name Dow Corning244fluid, or those sold under the name Mirasil CM5 by SACI-CFPA.

As other fatty substances, mention may be made of fatty acids such as stearic acid, fatty alcohols such as stearyl alcohol, cetostearyl alcohol and cetyl alcohol or derivatives thereof, waxes such as beeswax, carnauba wax or candelilla wax, and also gums, in particular silicone gums.

The ingredients of the oil phase may be selected by those skilled in the art in various ways in order to prepare a composition having the desired properties, such as consistency or texture.

The oily phase of the composition according to the invention preferably comprises a synthetic oil and/or a silicone oil, as synthetic oil, preferably an isopropyl palmitate, such as the product of the company Croda sold under the name Crodamol IPP, or an isopropyl myristate, such as the product of the company Crodamol sold under the name Crodamol IPM, as silicone oil, preferably dimethicone.

The oily phase of the emulsion according to the invention may be present in a content ranging from 3 to 50% by weight, preferably from 6 to 20% by weight, relative to the total weight of the composition.

The composition according to the invention comprises a surfactant-emulsifier. Among these, mention may be made, for example, of glyceryl/PEG 100 stearate from UNIQEMA, sold under the name Arlacel165FL, or glyceryl/PEG 100 stearate from SEPPIC, sold under the name Simulsol165, polyoxyethylated fatty acid esters such as Arlatone983 from UNIQEMA, or polyoxyethylated (2) stearyl alcohol, sold under the name Brij72, combined with polyoxyethylated (21) stearyl alcohol from UNIQEMA, sold under the name Brij 721; sorbitan esters are, for example, sorbitan oleate sold under the name Arlacel80 by ICI or Croda by Crill4, sorbitan sesquioleate sold under the name Arlacel83 by ICI or SEPPIC by Montane83, or sorbitan isostearate, fatty alcohol ethers.

The compositions according to the invention advantageously contain up to 15% by weight, preferably from 2 to 12% by weight, more particularly from 2 to 6% by weight, of suitable surfactant-emulsifiers, based on the total weight of the composition.

The composition according to the invention contains ivermectin in an amount of 0.001 to 10% by weight, based on the total weight of the composition. Preferably, the composition according to the invention comprises ivermectin in an amount of 0.1 to 5% by weight, relative to the total weight of the composition.

As examples of solvents and/or penetration enhancers for ivermectin active agents, mention may preferably be made of propylene glycol, alcohols such as ethanol, isopropanol, butanol, N-methyl-2-pyrrolidone or DMSO, polysorbate 80, phenoxyethanol or mixtures thereof.

The following table illustrates the solubility of ivermectin in different solvents:

the compositions of the present invention comprise from 0.1 to 20%, preferably from 1 to 10%, of a solvent for the ivermectin active agent and/or a penetration enhancer.

The compositions according to the invention may also contain from 0.01 to 5% by weight, based on the total weight of the composition, of an aqueous phase gelling compound. Among the gelling agents which can be used in the compositions according to the invention, mention may be made of carboxyvinyl polymers (carbomers), non-limiting examples being carbomer, Carbopol981, Carbopol ETD2020, Carbopol980, Carbopol Ultrez10NF and Pemulen TR1, marketed by the company NOVEON.

As the aqueous phase gelling agent, there may be mentioned cellulose derivatives such as hydroxypropylmethyl cellulose or hydroxyethyl cellulose, xanthan gum, aluminium/magnesium silicates such as Veegum K or Veegum Ultra sold by Vanderbilt, guar gum and its analogues, polyacrylamides such as the mixture polyacrylamide/C13-14 isoparaffin/laurylpolyoxyethyl (7) ether (laureth-7), such as the one sold under the name Sepigel305 by the company SEPPIC, or acrylamide mixtures, AMPS copolymer dispersions 40% isohexadecane under the name Simulgel600PHA, or modified starches such as Structure solvent sold by National Starch, or mixtures thereof.

The compositions of the invention preferably comprise from 0-01 to 5%, preferably from 0.1 to 3%, of a gelling agent.

As gelling agents according to the invention, it will be preferred to use substances made of carbomers, preferably Pemulen TR1 or aluminium/magnesium silicates such as Veegum K.

The composition of the invention also comprises from 30 to 95%, preferably from 60 to 80% by weight of water, based on the total weight of the composition. The water used in the composition according to the invention will preferably be pure water.

The pharmaceutical compositions according to the invention may also comprise inert additives or combinations of such additives, for example

-a flavour enhancer;

-a preservative;

-a stabilizer;

-a humidity regulator;

-a pH adjusting agent;

-an osmotic pressure regulator;

-UV-a and UV-B protectants;

-and an antioxidant.

Of course, one skilled in the art will be careful to select the optional compounds to be added to these compositions in such a way that the advantageous properties associated with the essence of the invention are not, or are not substantially, altered by the addition.

These additives may be present in the composition in an amount of from 0.001 to 20% by weight based on the total weight of the composition.

The compositions according to the invention advantageously contain:

a)6 to 20% of an oil phase;

b)2 to 12% of a surfactant-emulsifier;

c)0.1 to 5% of ivermectin;

d)0.1 to 20% of a solvent;

e)0.01 to 5% of a gelling agent;

f) and an emulsion of water.

The pH is preferably between 6.0 and 6.5. The natural pH of the mixture can be checked and possible corrections made with the neutralizer solution during one of the steps in the above preparation method can be carried out, depending on its chemical nature, with the addition of optional additives.

Examples of compositions that can be used according to the invention are illustrated in examples 1 to 6.

The subject of the present invention is also a composition for topical administration for human use, characterized in that it comprises:

a) an oil phase comprising fatty matter;

b) at least one surfactant-emulsifier;

c) ivermectin;

d) one or more solvents for the active agent and/or a penetration enhancer;

e) and an emulsion of water.

More particularly, this composition may contain:

a) an oil phase comprising fatty matter;

b) at least one surfactant-emulsifier;

c) ivermectin;

d) one or more solvents for the active agent and/or a penetration enhancer;

e) one or more gelling agents;

f) and water.

Preferably, the composition comprises:

a)6 to 20% of an oil phase;

b)2 to 12 surfactant-emulsifier;

c)0.1 to 5% of ivermectin;

d)0.1 to 20% of a solvent;

e)0.01 to 5% of a gelling agent;

f) and water.

These components are the substances defined above.

The composition examples of 1 to 6 illustrate the compositions according to the invention.

The subject of the invention is also the use of the composition according to the invention for the production of a pharmaceutical preparation for the treatment of skin disorders.

The use of ivermectin for the production of a pharmaceutical composition for topical administration to humans according to the invention is particularly suitable for the treatment of rosacea, acne vulgaris, seborrheic dermatitis (seborrhoeic), perioral dermatitis, papular rashes, transient acanthosis laxa and chestnut-like necrotic acne.

The use of ivermectin for the manufacture of a pharmaceutical composition for topical administration to humans according to the invention is more particularly suitable for the treatment of rosacea.

The stability and tolerability of the various formulations of compositions containing ivermectin, and also of the compositions obtained according to the invention, will now be given by way of illustration and not of limitation of their nature.

Example 1: composition 1

Examples 1 to 4 were carried out according to the following procedure:

in a first suitable vessel, the aqueous phase is weighed, mixed at 700rpm and heated to 65-70 ℃.

In a second suitable vessel, the oil phase is weighed, mixed at 425 and 475rpm and heated to 70-75 ℃.

In a third suitable container, the active phase is weighed and heated to 60-65 ℃.

When the oil and water phases are 70 ℃, the two phases are mixed with Rayneri at 900rpm with stirring until completely homogeneous and then cooled.

After cooling the emulsion to 55-65 ℃, the active phase is added with stirring at 600 rpm. The temperature was reduced to 30 ℃ at 600 rpm.

The pH was adjusted to 6.0.

Composition (I)	Is in the weight percent of the total weight of the composition
		Ivermectin	1.00
Glycerol	4.0
		Magnesium aluminum silicate	1.0
P-hydroxybenzoic acid methyl ester	0.2
		EDTA disodium salt	0.05
Citric acid monohydrate	0.05
		Palmitic acid isopropyl ester	4.0
Glycerol/PEG 100 stearate	3.0
		Self-emulsifying wax	2.0
Palm stearic acid (Palmitostearic acid)	2.5
		Stearyl polyoxyethylene (20) ether (Steareth-20)	3.0
Sorbitan stearate	2.0

Dimethicone 20	0.5
		Propyl p-hydroxybenzoate	0.1
Propylene glycol	4.0
		Glycerol triacetate	1.0
Phenoxyethanol	0.5
		10% sodium hydroxide	qs pH
Water (W)	qs100

Example 2: composition 2

Composition (I)	Is in the weight percent of the total weight of the composition
		Ivermectin	1.00
Glycerol	4.0
		Stearyl polyoxyethylene (2) ether (Steareth-2)	1.0
Stearyl polyoxyethylene (21) ether (Steareth-21)	2.0
		Magnesium aluminometasilicate/titanium dioxide/silicon dioxide	1.0
P-hydroxybenzoic acid methyl ester	0.2
		Propyl p-hydroxybenzoate	0.1
EDTA disodium salt	0.05
		Citric acid monohydrate	0.05
Palmitic acid isopropyl ester	4.0
		Glycerol/PEG 100 stearate	2.0
Self-emulsifying wax	1.0
		Palm stearic acid (Palmitostearic acid)	2.00
Dimethicone 200-350cs	0.5
		Propylene glycol	4.0
Glycerol triacetate	1.00
		Phenoxyethanol	0.5
10% sodium hydroxide	qs pH
		Water (W)	qs100

Example 3: composition 3

Composition (I)	Is in the weight percent of the total weight of the composition
		Ivermectin	1.00
Glycerol	4.0
		Acrylate C10-30 alkyl acrylate crosspolymer	0.15
P-hydroxybenzoic acid methyl ester	0.2
		EDTA disodium salt	0.05
Citric acid monohydrate	0.05
		Tetradecanoic acid isopropyl ester	4.0
Cetyl alcohol	3.0
		Stearyl alcohol	2.0
Self-emulsifying wax	0.8
		Palm stearic acid (Palmitostearic acid)	0.5
Stearyl polyoxyethylene (20) ether (Steareth-20)	2.0
		Sorbitan palmitate	1.0
Dimethicone 20	0.5
		Propyl p-hydroxybenzoate	0.1
Propylene glycol	4.0
		Glycerol triacetate	1.0
Phenoxyethanol	0.5
		10% sodium hydroxide	qs pH
Water (W)	qs100

Example 4: composition 4

Composition (I)	Is in the weight percent of the total weight of the composition
		Ivermectin	1.00
Glycerol	4.0
		Magnesium aluminum silicate	1.0
P-hydroxybenzoic acid methyl ester	0.2
		EDTA disodium salt	0.05
Citric acid monohydrate	0.05
		Palmitic acid isopropyl ester	4.0
Glycerol/PEG 100 stearate	3.0
		Self-emulsifying wax	2.0
Palm stearic acid (Palmitostearic acid)	3.0
		Stearyl polyoxyethylene (20) ether (Steareth-20)	3.0
Sorbitan palmitate	2.0
		Dimethicone 20	0.5
Propyl p-hydroxybenzoate	0.1
		Propylene glycol	4.0
Glycerol triacetate	1.0
		Phenoxyethanol	0.5
10% sodium hydroxide	qs pH
		Water (W)	qs100

Example 5: composition 5

Examples 5 and 6 were carried out according to the following procedure:

-an aqueous phase

In a first suitable beaker, the acrylate/C10-30 alkyl acrylate crosspolymer was dispersed in water with Rayneri stirring at 800rpm until a homogeneous gel was obtained. Heating to 65-70 deg.C is started, and then glycerin and additives are added.

-an oil phase

In a second suitable beaker, the oil phase components are combined and heated to 70 ℃ to 75 ℃ with Rayneri stirring at 400rpm for homogenization.

-an active phase

In a third suitable beaker, the active phase components (solvent + additives) are weighed.

Homogenised at about 500rpm and added to a magnetic rod.

Ivermectin is weighed in a weighing boat (weighing boat) and then added to the active phase beaker vessel.

The beaker was placed on a magnetic stirrer until the ivermectin dissolved.

When the oil and water phases are at 70 deg.C, the phases are mixed with Rayneri for 10 minutes with stirring at 900 rpm.

The emulsion was cooled to 40 ℃ and the active phase was added with stirring with Rayneri at 900rpm for 10 minutes. The temperature was reduced to 30 ℃ at 700 rpm.

The volume was made up with sufficient water and the pH was adjusted to 6.3 +/-0.3.

Composition (I)	Is in the weight percent of the total weight of the composition
		Ivermectin	1.00
Glycerol	4.0
		Acrylate C10-30 alkyl acrylate crosspolymer	0.2
P-hydroxybenzoic acid methyl ester	0.2
		EDTA disodium salt	0.05
Citric acid monohydrate	0.05
		Palmitic acid isopropyl ester	4.0
Cetyl alcohol	3.5
		Stearyl alcohol	2.5
Oleyl alcohol	2.0
		Cetostearyl polyoxyethylene (20) ether (Ceteaeth-20)	3.0
Sorbitan monostearate	2.0
		Dimethicone oil 20020cs	0.5
Propyl p-hydroxybenzoate	0.1
		Propylene glycol	2.0
Phenoxyethanol	1.0
		10% sodium hydroxide	qs pH
Water (W)	qs100

Example 6: composition 6

Composition (I)	Is in the weight percent of the total weight of the composition
		Ivermectin	1.4
Glycerol	4.0
		Acrylate C10-30 alkyl acrylate crosspolymer	0.2
P-hydroxybenzoic acid methyl ester	0.2
		EDTA disodium salt	0.05
Citric acid monohydrate	0.05
		Palmitic acid isopropyl ester	4.0
Cetyl alcohol	3.5
		Stearyl alcohol	2.5
Oleyl alcohol	2.0
		Cetostearyl polyoxyethylene (20) ether (Ceteaeth-20)	3.0
Sorbitan monoStearic acid ester	2.0
		Dimethicone oil 20020cs	0.5
Propyl p-hydroxybenzoate	0.1
		Propylene glycol	2.0
Phenoxyethanol	1.0
		10% sodium hydroxide	qs pH
Water (W)	qs100

Example 7: examples of the stability of the compositions described in examples 5 and 6

Determination of active agent content by HPLC by external calibration

The results, expressed as% recovery relative to theoretical values, indicate that ivermectin has very good chemical stability in compositions with time as variable (function).

Example 8: determination of ivermectin Change in the composition of example 5 with pH as variable Stability in learning

These results show that ivermectin has very good chemical stability in pH-dependent compositions.

Example 9: study of the tolerability and acceptability of the composition of example 5

A randomized single-blind in vivo study was performed in 15 people with rosacea affected skin. The composition of example 5 was tested and compared to gels and emulsions according to the invention having different combinations.

The individual himself is tested 3 times in order to apply different applications. During each visit, 2 of the three products were applied so as to encompass each half-side face (half-face). Each product was tested twice during the study. After application and each visit, individuals were filled out a questionnaire for each product tested to assess clinical tolerance and cosmetic acceptability.

The following clinical tolerability parameters were evaluated: stinging, burning, dry skin, tightness, or itching.

The following cosmetic acceptability parameters were evaluated: creaminess, texture, lack of oily and sticky feel, nourishing, comfort, and soft to the touch.

The compositions according to the invention were judged by the individual to be well tolerated for all the tolerability parameters, as well as for the other two compositions.

In general, for all acceptability parameters, 76.66% of the subjects in the tested cases gave their acceptance (good or excellent) of the parameters with respect to the composition of example 5. This formulation is therefore readily distinguishable by itself from the gel-emulsion composition, with 66.66% human support, and from the other emulsions, with 63.32% human support.

Example 10: irritation study after 21 days

A irritation study after 21 days was performed to determine the irritation caused by the three compositions determined in the above examples. No product was considered irritating under the conditions tested.

Claims

1. Use of ivermectin for the manufacture of a pharmaceutical composition for topical administration for the treatment of rosacea.

2. Use according to claim 1, characterized in that the composition is in the form of an emulsion, a gel or a solution of the cream or lotion type.

3. Use according to claim 1 or 2, characterized in that the composition is in the form of an emulsion.

4. Use according to any one of claims 1 to 3, characterized in that the composition contains from 0.001 to 10% by weight of ivermectin, relative to the total weight of the composition.

5. Use according to any one of claims 1 to 4, characterized in that the composition is a composition comprising:

a) an oil phase comprising fatty matter;

b) at least one surfactant-emulsifier;

c) ivermectin;

d) one or more solvents for the active agent and/or a penetration enhancer;

e) and an emulsion of water.

6. Use according to any one of claims 1 to 5, characterized in that the composition is a composition comprising:

a) an oil phase comprising fatty matter;

b) at least one surfactant-emulsifier;

c) ivermectin;

d) one or more solvents for the active agent and/or a penetration enhancer;

e) one or more gelling agents;

f) and an emulsion of water.

7. Use according to any one of claims 1 to 6, characterized in that the composition comprises:

a)6 to 20% of an oil phase;

b)2 to 12% of a surfactant-emulsifier;

c)0.1 to 5% of ivermectin;

d)0.1 to 20% of a solvent;

e)0.01 to 5% of a gelling agent;

f) and water.

8. Use according to any one of claims 5 to 7, characterized in that the oil phase contains synthetic oils and/or silicone oils.

9. Use according to claim 8, characterized in that the synthetic oil is isopropyl palmitate or isopropyl myristate.

10. Use according to any one of claims 5 to 9, characterized in that the surfactant-emulsifier is selected from glyceryl/PEG 100 stearate, polyoxyethylenated fatty acid esters, polyoxyethylenated (2) stearyl alcohol in combination with polyoxyethylenated (21) stearyl alcohol, sorbitan esters such as sorbitan oleate, sorbitan sesquioleate or sorbitan isostearate, and fatty alcohol ethers.

11. Use according to any one of claims 5 to 10, characterized in that the solvent is selected from propylene glycol, alcohols such as ethanol, isopropanol, butanol, N-methyl-2-pyrrolidone or DMSO, polysorbate 80, phenoxyethanol and mixtures thereof.

12. Use according to any one of claims 6 to 11, characterized in that the gelling agent is selected from carbomers or aluminium/magnesium silicates.

13. Use according to any one of the preceding claims, characterized in that the composition comprises, in water:

ivermectin 1.00 Glycerol 4.0 Acrylate C10-30 alkyl acrylate crosspolymer 0.2 P-hydroxybenzoic acid methyl ester 0.2 EDTA disodium salt 0.05 Citric acid monohydrate 0.05 Palmitic acid isopropyl ester 4.0 Cetyl alcohol 3.5 Stearyl monostearate 2.5 Oleyl alcohol 2.0 Hexadecyl/octadecyl polyoxyethylene (20) ether 3.0 Sorbitan monostearate 2.0 Dimethicone oil 20020cs 0.5 Propyl p-hydroxybenzoate 0.1 Propylene glycol 2.0 Phenoxyethanol 1.0 10% sodium hydroxide qs pH

Wherein the amounts refer to weight percent based on the total weight of the composition.

14. Use according to any one of the preceding claims, characterized in that the composition comprises, in water:

ivermectin 1.4 Glycerol 4.0 Acrylate C10-30 alkyl acrylate crosspolymer 0.2 P-hydroxybenzoic acid methyl ester 0.2 EDTA disodium salt 0.05 Citric acid monohydrate 0.05 Palmitic acid isopropyl ester 4.0 Cetyl alcohol 3.5 Stearyl alcohol 2.5 Oleyl alcohol 2.0 Hexadecyl/octadecyl polyoxyethylene (20) ether 3.0 Sorbitan monostearate 2.0 Dimethicone oil 20020cs 0.5 Propyl p-hydroxybenzoate 0.1 Propylene glycol 2.0 Phenoxyethanol 1.0 10% sodium hydroxide qs pH Water (W) qs100

15. A composition for topical administration to a human, characterized in that said composition is a composition comprising:

a) an oil phase comprising fatty matter;

b) at least one surfactant-emulsifier;

c) ivermectin;

d) one or more solvents for the active agent and/or a penetration enhancer;

e) and an emulsion of water.

16. Composition according to claim 15, characterized in that it comprises:

a) an oil phase comprising fatty matter;

b) at least one surfactant-emulsifier;

c) ivermectin;

d) one or more solvents for the active agent and/or a penetration enhancer;

e) one or more gelling agents;

f) and water.

17. Composition according to claim 15 or 16, characterized in that it contains:

a)6 to 20% of an oil phase;

b)2 to 12% of a surfactant-emulsifier;

c)0.1 to 5% of ivermectin;

d)0.1 to 20% of a solvent;

e)0.01 to 5% of a gelling agent;

f) and water.

18. Composition according to any one of claims 15 to 17, characterized in that it comprises, in water:

ivermectin 1.00 Glycerol 4.0 Acrylate C10-30 alkyl acrylate crosspolymer 0.2 P-hydroxybenzoic acid methyl ester 0.2 EDTA disodium salt 0.05 Citric acid monohydrate 0.05 Palmitic acid isopropyl ester 4.0 Cetyl alcohol 3.5 Stearyl alcohol 2.5 Oleyl alcohol 2.0 Hexadecyl/octadecyl polyoxyethylene (20) ether 3.0 Sorbitan monostearate 2.0 Dimethicone oil 20020cs 0.5 Propyl p-hydroxybenzoate 0.1 Propylene glycol 2.0 Phenoxyethanol 1.0 10% sodium hydroxide qs pH

19. Composition according to any one of claims 15 to 17, characterized in that it comprises, in water:

20. Use of a composition according to any one of claims 15 to 19 in the manufacture of a pharmaceutical product for the treatment of a skin condition.

21. Use according to claim 20, characterized in that the pharmaceutical product is for the treatment of rosacea, acne vulgaris, seborrheic dermatitis, perioral dermatitis, papuloid rash, transient acanthosis laxa dermatosis and chestnut-like necrotic acne.

22. Use according to one of claims 20 and 21, characterized in that the pharmaceutical product is for the treatment of rosacea.