WO2000038646A1

WO2000038646A1 - Dermatological compositions containing tannic acid and a microbial proliferation inhibitor

Info

Publication number: WO2000038646A1
Application number: PCT/EP1999/010192
Authority: WO
Inventors: Alain E. Fructus; Adrian Shephard; Robert Arthur Sherry; Gérard SULTAN
Original assignee: The Boots Company Plc
Priority date: 1998-12-23
Filing date: 1999-12-21
Publication date: 2000-07-06
Also published as: FR2787709A1; AU3041500A

Abstract

Dermatological and/or cosmetic composition comprises an effective combination of tannic acid and first microbial proliferation inhibitor which comprises an aqueous mixture of sodium polyacrylate, at least one polyol and at least one polyalkylene glycol compound. The invention relates to the local or topical application of this composition as well as its use as a medicament, in particular for the treatment of the symptoms of psoriasis, atopy and acne.

Description

DERMATOLOGICAL COMPOSITIONS CONTAINING TANNIC ACID AND A MICROBIAL PROLIFERAΗON INHIBITOR

The present invention relates to a dermatological and/or cosmetic composition for the treatment of skin disorders such as acne.

The present invention therefore provides a dermatological and/or cosmetic composition for the treatment of acne, said composition being characterised in that it contains an effective combination of tannic acid and a microbial proliferation inhibitor which comprises an aqueous mixture of sodium polyacrylate, at least one polyol and at least one polyalkyleneglycol compound. The invention also relates to a dermatological and cosmetic composition which may contain, in addition, at least one distillate of witch hazel (Hamamelis virginiana).

Another object of the present invention is the use of this dermatological and cosmetic composition as described above for the treatment of the symptoms of psoriasis.

Another object of the present invention is the use of this dermatological and cosmetic composition as described above for the treatment of the symptoms of atopy.

Another object of the present invention is the use of this dermatological and cosmetic composition as described above for the treatment of the symptoms of acne.

This invention as described above is more particularly intended for cosmetic or dermatological use. More particularly, this dermatological or cosmetic composition according to the invention is applied by topical route.

The invention also relates to the use of this dermatological composition described above as a medicament as well as the use of its constituents for the preparation of a medicament intended for the treatment of the symptoms described above.

Tannic acid is preferably present in an amount from 0.001 to 0.05, preferably 0.005 to 0.025, more preferably 0.010 to 0.020 % by weight of the compositions of the present invention. Tannic acid is available commercially for example in the form of an aqueous/alcoholic extract sold under the trade name Tanlex VE or in the form of an aqueous/butylene glycol extract under the trade name Tanlex VB.

The microbial proliferation inhibitor is an aqueous mixture of sodium polyacrylate, at least one polyol and at least one polyalkyleneglycol compound.

The polyol may be a diol or triol containing 3 to 8 carbon atoms (for example propylene glycol, 1 ,3-butylene glycol, 1 ,2-pentanediol, 1 ,2-octanediol (INCI name caprylyl glycol), 1 ,8-octanediol, 2-ethyl-1 ,3-hexanediol, glycerine (1 ,2,3- propanetriol), mannitol, sorbitol or mixtures thereof). Preferably the polyol is a mixture of glycerine and caprylyl glycol.

Preferred polyalkyleneglycols include polyethyleneglycols (for example PEG-8) and polypropyleneglycols.

The amounts of the components of the first microbial proliferation inhibitor present as percentages by weight of the first microbial inhibitors are

sodium polyacrylate 0.2 to 1 % (preferably 0.5 to 0.8% most preferably 0.6 to 0.7%) polyol 40 to 70% (preferably around 50 to 60%) polyalkyleneglycols 0 to 35% (preferably 10 to 30, most preferably 15 to 25%)

An examples of a suitable microbial proliferation inhibitor is a combination of sodium polyacrylate (0.65%), glycerine (50%), PEG-8 (20%), caprylyl glycol

(6%) and aqua (to 100%) sold by the Sederma company under the denomination Osmocide 2^®. The concentrations of this commercially available material can generally vary from 5 to 25% by weight, the preferred concentrations are usually situated between 10 to 20% by weight relative to the total weight of the composition.

The above-mentioned compositions according to the invention can be incorporated into an oil-in-water emulsion, or a water-in-oil emulsion, a water- in-silicone fluid emulsion or a water-in-oil-in-water multiple emulsion. Emulsions contain an oil phase an aqueous phase and an emulsifier to form and stabilise the emulsion. Alternatively the compositions of the present invention may be incorporated into a gel or a pseudo-emulsion (dispersion of two non-miscible phases using gelling agents).

The oil phase of emulsions according to the present invention can contain for example:

1) hydrocarbon oils such as paraffin or mineral oils such as isohexadecane and isododecane;

2) natural oils such as sunflower oil, evening primrose oil, jojoba oil, hydrogenated castor oil, avocado oil, hydrogenated palm oil;

3) natural triglycerides such as caprylic/capric triglyceride, caprylic/capric linoleic triglyceride, caprylic/capric succinic triglyceride;

4) silicon fluids such as cyclomethicone, dimethicone and dimethiconol;

5) fatty alcohols such as stearic alcohol, cetyl alcohol, hexadecylic alcohol; 6) fatty acids such as stearic acid, palmitic acid;

7) esters of fatty acids such as dioctyl succinate, glyceryl dioleate, myristyl myristate and isopropyl myristate;

8) waxes such as beeswax, paraffin, carnauba wax, ozokerite;

9) lanolin and its derivatives (oil, alcohol, waxes);

10) their mixtures.

The oil phase preferably comprises approximately 5 to 30% and preferably 10 to 20% by weight of the composition.

The emulsifiers which can be used in the emulsions according to the present invention can be selected from the emulsifiers known in the prior art as being suitable for use in the types of emulsions listed above. Suitable emulsifiers include:-

1) The sucroesters such as saccharose cocoate and saccharose distearate; 2) The esters of sorbitan and the esters of ethoxylated sorbitan such as sorbitan stearate or polysorbate; 3) The esters of glycerols, the esters of ethoxylated glycerols and polyglycerols such as glyceryl oleate or PEG-20 glyceryl stearate or polyglyceryl-10-stearate; 4) The ethoxylated fatty alcohols such as ceteth-12 or steareth-6;

5) The sesquioleates such as sorbitan sesquioleate;

6) The emulsifiers based on silicon fluid such as silicon polyols;

7) The ethoxylated sterols of soya; or a mixture of one or more of the emulsifiers mentioned above.

The quantity of emulsifiers optionally present in the oil-in-water or the water-in- oil compositions of the present invention is, preferably, from 0.5 to 15% by weight of the composition. The quantity of emulsifiers present in the water-in- oil-in-water multiple emulsion is, preferably approximately 7 to 20% by weight of the composition. The oil phase of pseudoemulsions according to the present invention may comprise any of the materials listed above as the oil phase of emulsions.

The gels or pseudo-emulsions can be prepared by using one or a combination of several gelling agents selected from the gelling agents acceptable in cosmetic or dermatological products. These gelling agents can also, if desired be incorporated into the emulsions of the present invention. Examples of suitable gelling agents include:-

1) polysaccharide gums such as the derivatives of modified celluloses, derivatives of carraghenans, derivatives of alginates and derivatives of guar;

2) polysaccharide gums obtained from the fermentation of bacteria such as Xanthan gum, Sclerotium gum and Gellan gum;

3) acrylic polymers such as carbomers, polyacrylates, polymetacrylates and their derivatives;

4) quatemized polymers;

5) PVP's and polymers derived from PVP; and

6) mixtures thereof.

In the preferred pseudo-emulsion or in gelled emulsions according to the present invention, the gelling agent or combination of gelling agents represents approximately 0.1 to 30% and preferably approximately 0.25 to 25% by weight of the composition.

In addition, the compositions according to the present invention may contain one or more other compounds which will be known by persons skilled in the art, for example:

1) electrolytes for the stabilization of the water-in-oil emulsion such as sodium chloride or magnesium sulphate, preferably in a quantity ranging from 0.2 to 4% by weight of the composition;

2) moistening agents such as glycerine or propylene glycol or PEG or sorbitol, preferably in a quantity ranging from 1 to 10% by weight of the composition; 3) sequestering agents such as tetrasodium EDTA, preferably in a quantity ranging from 0.01 to 0.5% by weight of the composition; 4) softeners such as the ethers of fatty acids or the esters of fatty acids, preferably in a quantity ranging from 0.5 to 10% by weight of the composition;

5) hydrating agents such as hyaluronic acid, NaPCA, preferably in a quantity ranging from approximately 0.01 to 5% by weight of the composition;

6) film forming agents to facilitate spreading over the surface of the skin, such as the hydrolysates of the proteins of oats, wheat, collagen and almond, preferably in a quantity ranging from approximately 0.1 to 5% by weight of the composition; 7) insoluble pigments such as titanium oxide, rutile titanium oxide, octahedrite titanium oxide, pyrogenic titanium oxide, micronized titanium oxide, titanium oxide surface treated with silicons or with amino acids, or with lecithins, or with metallic stearates, iron oxide, iron oxide surface treated with silicons or with amino acids, or with lecithin, or with metallic stearates, zinc oxide, micronized zinc oxide, mica covered with titanium oxide, preferably in a quantity ranging from approximately 0.5 to 5% by weight of the composition;

8) preservatives such as methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, phenoxyethanol, 2-bromo-2-nitropropane-1 ,3-diol or mixtures thereof, preferably in a quantity ranging from about 0.05 to about 3 percent by weight of aid composition,

9) perfumes, preferably in a quantity ranging from about 0.05 to about 0.6 percent of said composition, 10) colorants, preferably in a quantity ranging from a trace to about

3x10-³ percent by weight of said composition, or 11) mixtures thereof.

The invention is illustrated by the following Examples which are given by way of example only. In the Examples that follow the amounts of each component are expressed as percentages by weight of the total composition.

Example 1 :

A dermatological composition was prepared from the following components:

Water phase components

Water to 100

Sodium carbomer 0.1

Acrylates/C_10.30 alkyl acrylate crosspolymer (Pemulin) 0.3

A mixture of glyceryl polymethacrylate (98.26%), propylene glycol (ca 1 %) and PVM/MA copolymer (0.6%) sold under the trade name Lubrajel 2.0

A mixture of glycerine (50%), sodium polyacrylate (0.65%), PEG-8 (20%), caprylyl glycol (6%) and water sold under the trade name Osmocide 2 15.0

Polymethyl methacrylate 1.5

Tannic acid 0.015

Hamamelis virginiana 0.15 Allantoin 0.1

Ammonium glycyrrhizate 0.05

Tetrasodium EDTA 0.05 Preservatives

Phenoxyethanol 0.3

Methylparaben 0.2

Propylparaben 0.1

Oil phase components

Dimethicone 3.0

Cetyl alcohol 2.0

Isononyl isononanoate 2.0 Isohexadecane 2.0

Hydrogenated coco-glycerides 1.0

Tocopherol acetate 0.2

The sodium carbomer and acrylates (C_10.30 alkyl acrylate crosspolymer) were stirred with water to form a gel which was heated to 75°C. The preservatives, the mixture of glyceryl polymethacrylate, propylene glycol and PVM/MA copolymer (Lubrajel) and the mixture of glycerine, sodium polyacrylate, PEG-8, caprylyl glycol and water (Osmocide 2) were added. The remaining water phase components were then added. The oil phase components were mixed in a separate vessel and then added to the rest of the composition and homogenised to form a gelled pseudoemulsion.

The microbial proliferation inhibitory activity of a material can be determined by measuring its minimal inhibitory concentration (MIC). This corresponds to the smallest quantity of the material required to completely inhibit the growth of the micro-organism tested. The compositions of the present invention were investigated to determine their MIC against Propionbacterium acnes and Pityrosporum ovale. Method for determining the minimal inhibitory concentration (MIC) :

Preparation of the innoculum

The innoculum is produced by innoculating a pure strain of the relevant microorganism in a suitable liquid medium. The concentration of the innoculum is such that after incubation under the experimental conditions given below, it would produce 10 colony forming units (cfu)/ml of microorganisms. The quantity of microorganisms in the innoculum may be determined by spectrophotometry.

Preparation of standard solutions of the materials to be tested

A tannic acid solution (an aqueous alcoholic solution of tannic acid sold under the trade name Tanlex VE) is taken and used to prepare a series of standard solutions of varying concentrations which are added to the Mueller Hinton gelose nutrient medium.

A microbial proliferation inhibitor (identified as MPI in the tables), a mixture of glycerine (50%), sodium polyacrylate (0.65%), PEG-8 (20%), caprylyl glycol

(6%) and water sold under the trade name Osmocide 2, is taken and used to prepare a second series of standard solutions of varying concentrations.

Standard solutions containing various concentrations of tannic acid and the MPI were also prepared.

A quantity of Mueller Hinton gelose nutrient medium is melted and mixed with the standard solutions of the materials to be tested and an amount distributed into each petri dish. When the medium is set, an aliquot of the innoculum of the microorganism is added onto the surface of the medium using a multi-point innoculator. The dishes were then incubated under the conditions set out below:- P. acnes - the dishes were incubated for 5 days at

37°C in an anerobic atmosphere P. ovale - the dishes were incubated for 72 hours at

30°C in an anerobic atmosphere

After incubation the petri dishes were examined. Those in which no culture is visible is ascribed as '-' in the relevant table, those in which a culture is visible are ascribed as '+'. "NT" in the tables indicates that the test has not been performed.

The tannic acid, MPI and the mixtures thereof identified in the tables below were tested for their inhibitory effect on the proliferation of Propionibacterium acnes and Pityrosporum ovale (which is also known as Malassezia furfur) which are the two main organisms involved in acne.

Table 1 MIC of Tannic Acid

Table 2 MIC of MPI

Table 3 MIC of combinations of tannic acid and MPI

From the data presented in Table 1 it can be seen that the MIC for the tannic acid solution was 0.5% (ie greater than 0.4%) against Propionibacterium acnes and 0.2% (ie greater than 0.1%) against Pityrosporum ovale. From the data presented in Table 2 the MIC for the microbial proliferation inhibitor was 30% (ie greater than 25%) against P acnes and 15% (ie greater than 13%) against P ovale.

When combinations of tannic acid solution and the microbial proliferation inhibitor were tested to determine the MIC against the test organisms (see Table 3) it was found that 0.3% tannic acid solution and 25% of the microbial proliferation inhibitor were sufficient to prevent growth of P acnes. Similarly, 0.1 % tannic acid solution and 13% of the microbial proliferation inhibitor were sufficient to prevent growth of Pityrosporum ovale. Individually these levels of tannic acid solution and the microbial proliferation inhibitor were ineffective at preventing microbial growth of each test organism. The data presented shows that there is a synergistic effect in reducing the MIC against both P acnes and P ovale.

Claims

1. Dermatological and/or cosmetic composition for the treatment of acne, said composition being characterised in that it contains an effective combination of tannic acid and a microbial proliferation inhibitor which comprises an aqueous mixture of sodium polyacrylate, at least one polyol and at least one polyalkylenglycol compound

2. Composition according to claim 1 in which the polyol is a diol or triol containing 3 to 8 carbon atoms

3. Composition according to claim 2 in which the polyol is selected from propylene glycol, 1 ,3-butylene glycol, 1 ,2-pentanediol, 1 ,2-octanediol, 1 ,8- octanediol, 2-ethyl-1 ,3-hexanediol, glycerine (1 ,2,3-propanetriol), mannitol, sorbitol or mixtures thereof.

4. Composition according to claim 3 in which the polyol is a mixture of glycerine and caprylyl glycol

5. Composition according to claim 1 in which the polyalkyleneglycol compound is selected from polyethyleneglycols and polypropyleneglycols.

6. Composition according to any one of the preceding claims, in which the microbial proliferation inhibitor is a mixture of sodium polyacrylate, glycerine, caprylyl glycol, PEG-8 and aqua.

7. Composition according to any one of the preceding claims, in which the microbial proliferation inhibitor is present in a quantity of approximately 0.25 to 30% by weight of the composition.

8. Composition according to claim 6, in which the mixture of sodium polyacrylate, glycerine, caprylyl glycol, aqua and PEG-8 is present in a quantity of 10 to 20% by weight of the total composition.

9. Composition according to any preceding claim in which the tannic acid is present in a quantity of 0.001 to 0.05% by weight of the total composition.

10. Composition according to any one of the preceding claims, characterised in that the said composition is in the form of a pseudo-emulsion, or an oil-in- water emulsion, or a water-in-oil emulsion, or a water-in-silicon fluid emulsion, or a gel, or a water-in-oil-in-water multiple emulsion.

11. Composition according to claim 10, characterised in that the said composition is in the form of a pseudo-emulsion or an oil-in-water emulsion.

12. Local or topical application of the composition according to any one of claims 1 to 11.

13. Use of a composition according to any one of claims 1 to 11 as a medicament.

14. Use of a composition according to any one of claims 1 to 11 for the preparation of a medicament intended for the treatment of the symptoms of psoriasis, for treatment of the symptoms of atopy and for the treatment of the symptoms of acne.