WO2010003828A2

WO2010003828A2 - Antiperspirant products

Info

Publication number: WO2010003828A2
Application number: PCT/EP2009/057945
Authority: WO
Inventors: Jean-Philippe André Roger COURTOIS; Clive Roderick Harding; Mark Harker; Iain Andrew Weddell
Original assignee: Unilever Plc; Unilever N.V.; Hindustan Unilever Limited
Priority date: 2008-07-08
Filing date: 2009-06-25
Publication date: 2010-01-14
Also published as: WO2010003828A3; AR072476A1

Abstract

A method of reducing perspiration in the axilla comprising the application to the axilla of a polypeptide or derivative thereof comprising the amino acid sequence GIu.GIu.Met.GIn.Arg.Arg.Ala.

Description

Antiperspirant Products

This invention relates to the field of cosmetic products, in particular antiperspirant products. This invention also relates to methods of reducing perspiration upon the surface of the human body.

Cosmetic compositions used for reducing perspiration often comprise an astringent metal salt, such as aluminium or zirconium salt. Such salts reduce perspiration by blocking sweat pores. This is an effective method of reducing perspiration, but not beyond improvement. For example, astringent metal salts can be perceived as harsh or irritating by some consumers.

There is a continuing requirement for effective perspiration reduction, particularly by agents that do not block sweat pores. The problem to be solved is the provision of effective or improved sweat control via the use of a cosmetically acceptable composition or compositions.

Polypeptides are disclosed in numerous cosmetic compositions for various purposes in the prior art. WO 06/094193 (Revance Therapeutics Inc.) discloses compositions comprising GIu . GIu .Met . GIn . Arg. Arg. for many uses, including the treatment of hyperhidrosis .

The use of the peptide GIu . GIu .Met . GIn .Arg. Arg. Ala . as a cosmetic ingredient for the treatment of wrinkles has been disclosed in trade literature published by Lipotec SA. The use of the peptide GIu . GIu .Met . GIn . Arg. Arg. Ala . Asp . as a cosmetic ingredient for the treatment of wrinkles has been disclosed in trade literature published by Lipotec SA.

The present invention is largely concerned with cosmetic compositions and methods.

According to a first aspect of the present invention, there is provided a non-therapeutic method of reducing perspiration in the axilla comprising the application to the axilla of a polypeptide or derivative thereof comprising the amino acid sequence: GIu . GIu .Met . GIn .Arg. Arg. Ala .

According to a second aspect of the present invention, there is provided a non-therapeutic method of reducing perspiration of the feet comprising the application to the feet of a polypeptide or derivative thereof comprising the amino acid sequence: GIu . GIu .Met . GIn .Arg. Arg. Ala .

According to a third aspect of the present invention, there is provided a cosmetic composition comprising a polypeptide or derivative thereof comprising the amino acid sequence: GIu . GIu .Met . GIn .Arg. Arg. Ala . and an astringent salt of aluminium and/or zirconium.

According to a fourth aspect of the present invention, there is provided a cosmetic composition comprising a polypeptide or derivative thereof comprising the amino acid sequence: GIu . GIu .Met . GIn .Arg. Arg. Ala . and an anti-microbial deodorant agent . According to a fifth aspect of the present invention, there is provided a method for the manufacture of a cosmetic composition comprising the co-formulation of a polypeptide or derivative thereof comprising the amino acid sequence: GIu . GIu .Met . GIn . Arg. Arg. Ala . and an astringent salt of aluminium and/or zirconium.

According to a sixth aspect of the present invention, there is provided the use of a polypeptide or derivative thereof comprising the amino acid sequence:

GIu . GIu .Met . GIn .Arg. Arg. Ala . for the manufacture of a medicament for the treatment of sweating, in particular excessive sweating or hyperhydrosis .

The method of controlling perspiration offered by the invention is particularly useful because the benefit can extend for a considerable period of time, often greater than 24 hours and sometimes even up to 4 days after application or longer. Significant deodorancy benefits may also accrue from the use of the present invention, in particular the use of products according to the third or fourth aspects of the invention (vide supra) .

The method of controlling perspiration and compositions according to present invention are particularly useful when direct application to the surface of the human body is involved. This is especially true when application to the axillae and/or feet is involved. Application to the axillae is most preferred because of the high concentration of eccrine sweat glands in these regions of the human body. -A-

In this description, the term "comprising" should be understood to be non-exhaustive, i.e., meaning that other components may also be present.

Polypeptides suitable for use in accordance with the present invention comprise the amino acid sequence:

GIu . GIu .Met . GIn . Arg. Arg. Ala . Other amino acids may also be present in the polypeptide, provided that they do not interrupt the above sequence. It is highly preferred that the polypeptide is water soluble (vide infra) .

It is preferred that the polypeptide is of 12 amino acid residues or less, more preferably 10 amino acid residues or less, and most preferably 8 amino acid residues or less. It has been found that longer polypeptides have at least the potential for causing undesirable responses on application to the human body.

The stereochemistry of the amino acids of the polypeptide is typically L-. Polypeptides suitable for use in accordance with the present invention typically comprise the amino acid sequence : L-GIu. L-GIu. L-Met . L-GIn . L-Arg. L-Arg. Ala .

In this description, the term "polypeptide" should be understood to mean "polypeptide or derivative thereof". "Derivatives thereof" are typically esters, amides, or salts. Acetate esters are a particular example. Certain polypeptide derivatives hydrolyse on application to yield the parent polypeptide. In this description, the term "water soluble" should be understood to refer to materials having a solubility in water at 25°C of 1 g/L or greater. Preferred polypeptides have a water solubility of 5g/L or greater and particularly preferred polypeptides have a water solubility of 10g/L or greater .

Preferred polypeptides have one of the following specific amino acid sequences: GIu . GIu .Met . GIn . Arg. Arg. Ala . or GIu . GIu .Met . GIn .Arg. Arg. Ala .Asp . These peptides are commercially available as acetate derivatives from Lipotec SA under the tradenames SNAP-7 and SNAP-8 respectively. The structures of these materials may be represented as: Ac-Glu-Glu-Met-Gln-Arg-Arg-Ala-NH₂ and Ac-Glu-Glu-Met-Gln-Arg-Arg-Ala-Asp-NH₂ respectively.

A particularly preferred polypeptide has the amino acid sequence : GIu. GIu. Met. GIn .Arg. Arg. Ala .Asp .

The polypeptide is preferably incorporated into a composition in an amount of from 0.0005 to 1%, particularly from 0.001 to 0.5%, and especially from 0.005 to 0.2% by weight of the composition. These levels of incorporation are extremely low when compared to conventional antiperspirant agents and allow space for significant levels of other components within compositions for use in accordance with the present invention (vide infra) .

In certain aspects of the present invention, the polypeptide may be used in conjunction with a further antiperspirant agent . In these aspects of the invention, the further antiperspirant agent may enhance the antiperspirant performance of the polypeptide.

When the polypeptide is used in conjunction with a further antiperspirant agent, it is not essential that the two are part of the same composition. Independent application of the two materials may be employed. Such application may be concurrent or consecutive, provided that the treated surface experiences the presence of both materials. When the actives are applied from independent compositions, it is preferred that the product also comprises a means for, and/or instruction for, both of the compositions to be applied to the surface requiring treatment.

The further antiperspirant active may be an astringent salt of aluminium and/or zirconium. When employed, such an astringent salt of aluminium and/or zirconium is preferably incorporated into a composition in an amount of from 0.5- 60%, particularly from 5 to 30% or 40%, and especially from 5 or 10% to 30 or 35% of the weight of the composition.

When employed, the astringent salt of aluminium and/or zirconium is preferably incorporated into a composition in an amount of from 0.5-60%, particularly from 5 to 30% or 40% and especially from 5 or 10% to 30 or 35% of the weight of the composition.

When employed, the ratio of the applied amount of astringent salt of aluminium and/or zirconium to the applied amount of polypeptide is preferably from 10:1 to 1000:1 and preferably 100:1 or greater.

Preferred astringent salts of aluminium and/or zirconium are aluminium, zirconium and aluminium/zirconium halides and halohydrate salts, such as chlorohydrates .

Aluminium halohydrates are usually defined by the general formula AI₂ (OH) _xQ_y . WH₂O in which Q represents chlorine, bromine or iodine, x is variable from 2 to 5 and x + y = 6 while WH2O represents a variable amount of hydration. Especially effective aluminium halohydrate salts, known as activated aluminium chlorohydrates, are described in EP 006,739 (Unilever PLC and NV) . Aluminium halohydrates as described herein are particularly preferred in aerosol compositions .

Zirconium actives can usually be represented by the empirical general formula: ZrO (OH) ₂n-nz^Bz • WH₂O in which z is a variable in the range of from 0.9 to 2.0 so that the value 2n-nz is zero or positive, n is the valency of B, and B is selected from the group consisting of chloride, other halide, sulphamate, sulphate and mixtures thereof. Possible hydration to a variable extent is represented by WH₂O. Preferable is that B represents chloride and the variable z lies in the range from 1.5 to 1.87.

The above aluminium and zirconium salts may have coordinated and/or bound water in various quantities and/or may be present as polymeric species, mixtures or complexes. In particular, zirconium hydroxy salts often represent a range of salts having various amounts of the hydroxy group. Zirconium aluminium chlorohydrate may be particularly preferred.

Antiperspirant complexes based on the above-mentioned astringent aluminium and/or zirconium salts can be employed. The complex often employs a compound with a carboxylate group, and advantageously this is an amino acid. Examples of suitable amino acids include dl-tryptophan, dl- phenylalanine, dl-valine, dl-methionine and alanine, and preferably glycine.

It is desirable to employ complexes of a combination of aluminium halohydrates and zirconium chlorohydrates together with amino acids such as glycine, which are disclosed in US 3,792,068 (Procter and Gamble Co.) . Certain of those Al/Zr complexes are commonly called ZAG in the literature. ZAG actives generally contain aluminium, zirconium and chloride with an Al/Zr ratio in a range from 2 to 10, especially 2 to 6, an Al/Cl ratio from 2.1 to 0.9 and an amount of glycine.

The proportion of astringent salts of aluminium and/or zirconium in a composition normally includes the weight of any water of hydration and any complexing agent that may also be present in the solid active. However, when the active salt is in solution, its weight excludes any water present .

If the composition comprising the astringent salt of aluminium and/or zirconium is in the form of an emulsion the antiperspirant active will be dissolved in the disperse phase. In this case, the antiperspirant active will often provide from 3 to 60% by weight of the aqueous disperse phase, particularly from 10% or 20% up to 55% or 60% of that phase.

Alternatively, the composition comprising the astringent salt of aluminium and/or zirconium may take the form of a suspension in which antiperspirant active in particulate form is suspended in the water-immiscible liquid carrier. Such a composition will generally not have any separate aqueous phase present and may be referred to as "anhydrous" although it should be understood that some water may be present bound to the antiperspirant active. In such compositions, the particle size of the antiperspirant salts often falls within the range of 0.1 to 200 μm with a mean particle size often from 3 to 20 μm.

A further antiperspirant agent may be a calcium channel blocking agent, as described for example in WO 02/11690

(Unilever, et al) . Preferred calcium channel blocking agent suitable for use as a further antiperspirant agent are magnesium salts, in particular magnesium gluconate.

A further antiperspirant agent may be a further polypeptide having antiperspirant activity. That is to say, the further antiperspirant agent may be a polypeptide other than one that comprises the amino acid sequence: GIu . GIu .Met . GIn . Arg. Arg. Ala . Suitable polypeptides are described in the following paragraphs. A suitable further antiperspirant agent is a polypeptide comprising the amino acid sequence: Tyr . Ala . GIy . Phe . Leu . polypeptides of this sort are disclosed for the treatment of skin wrinkles in WO 06/106164 (Lipotec SA) . A preferred polypeptide of this type is the tetrapeptide

Tyr .Ala . GIy . Phe . Leu . The amino acids in polypeptides of this type are typically L-, with the exception of the specified alanine amino acid, which is typically D-.

A suitable further antiperspirant agent is a peptide comprising the structure: β-Ala-Pro-Dab, where "Dab" is diaminobutyroylbenzylamide . Peptides of this type are disclosed in WO 06/047900 (Pentapharm AG) . A preferred peptide of this type, commercially available from Pentapharm AG as SYN^®-AKE and having the structure: β-Ala-Pro-Dab, is disclosed as suitable for topical application against hyperhidrosis in Research Disclosure, Vol. 519, 07 2007, p. 685.

A particular component that may enhance the antiperspirancy performance of the polypeptide is a lamellar phase stabilised oil-in-water emulsion. Such emulsions are sometimes known as oleosome dispersions. Typically, they comprise dispersed droplets of oil surrounded by multiple layers of liquid crystalline lamellar phase comprised of one or more surfactants.

The oil of the oleosome dispersions should preferably remain in a liquid state at temperatures as low as 20⁰C or even 15°C. For this reasons, typical oils have melting point from their solid state of less than 20⁰C, preferably less than 15°C, and more preferably less than 10⁰C.

Preferred oils should be relatively fluid, having a kinematic viscosity of less than 100 cSt (mm²/s) and preferably less than 50 cSt (mm²/s) at 20⁰C.

Suitable oils include hydrocarbon oils and ester oils, particularly triglyceride oils, such as sunflower seed oil. Other particular oils that might be used in the oleosomes are C₁₂-₁₅ alkyl benzoate esters, hydrogenated polybutene, PPG-14 butyl ether, triethyl citrate, isopropyl palmitate, and isopropylmyristate .

The lamellar phase of the oleosome dispersion is typically comprised of two non-ionic surfactants, one having a relatively low HLB (less than 8 and preferably less than 5) and one having a relatively high HLB (more than 12 and preferably more than 15) . The ratio high HLB surfactant to low HLB surfactant is chosen so as to give a stable oleosome dispersion, typically ratios being from 1:1 to 1:6 by weight, respectively. A blend of steareth-2 and steareth-20 has been found to be suitable, particularly when used in combination with sunflower oil. Steareth-2 and steareth-20 are best used at a ratio of from 1:4 to 1:5 by weight.

The oleosome dispersions have an oil content that typically makes up from 1 to 30%, preferably from 1 to 20%, and more preferably from 1 to 10% by weight of the total composition. The surfactant content typically makes up from 1 to 30%, preferably from 1 to 20%, and more preferably from 1 to 10% by weight of the composition. The ratio of oil to surfactant is typically from 1:3 to 3:1 and preferably from 1:2 to 2:1.

An anti-microbial deodorant agent is a preferred additional component of compositions suitable for use in accordance with the present invention. The anti-microbial deodorant agent may be a bacteriocidal agent or a bacteriostatic agent. Synergistic deodorancy benefits may be achieved using compositions comprising an anti-microbial deodorant agent .

Preferred anti-microbial deodorant agents are organic in nature and such anti-microbial deodorant agents are particularly preferred in compositions that do not comprise an astringent salt of aluminium and/or zirconium.

When employed, the anti-microbial deodorant agent is typically incorporated into the composition at from 0.01% to 3% and particularly at from 0.03% to 0.5%.

Preferred anti-microbial deodorant agents have a minimum inhibitory concentration (MIC) of 1 mg.ml^"1 or less, particularly 200 μg.ml^"1 or less, and especially 100 μg.ml^"1 or less. The MIC of an anti-microbial agent is the minimum concentration of the agent required to significantly inhibit microbial growth. Inhibition is considered "significant" if an 80% or greater reduction in the growth of an inoculum of Staphylococcus epidermidis is observed, relative to a control medium without an anti-microbial agent, over a period of 16 to 24 hours at 37⁰C. Details of suitable methods for determining MICs can be found in "Antimicrobial Agents and Susceptibility Testing", C . Thornsberry, (in "Manual of Clinical Microbiology", 5^th Edition, Ed. A. Balows et al, American Society for Microbiology, Washington D. C, 1991) . A particularly suitable method is the Macrobroth Dilution Method as described in Chapter 110 of above publication (pp. 1101-1111) by D. F. Sahm and J. A. Washington II. MICs of anti-microbials suitable for inclusion in the compositions of the invention are triclosan: 0.01-10 μg.ml^"1 (J.Regos et al., Dermatologica

(1979) , 158: 72-79) and farnesol: ca. 25 μg.ml^"1 (K. Sawano, T. Sato, and R. Hattori, Proceedings of the 17^th IFSCC International Conference, Yokahama (1992) p.210-232) . By contrast ethanol and similar alkanols have MICs of greater than 1 mg.ml

Suitable organic anti-microbials are bactericides, for example quaternary ammonium compounds, like cetyltrimethylammonium salts; chlorhexidine and salts thereof; and diglycerol monocaprate, diglycerol monolaurate, glycerol monolaurate, and similar materials, as described in "Deodorant Ingredients", S.A.Makin and M.R.Lowry, in "Antiperspirants and Deodorants", Ed. K. Laden (1999, Marcel Dekker, New York) . More preferred anti-microbials for use in the compositions of the invention are polyhexamethylene biguanide salts (also known as polyaminopropyl biguanide salts) , an example being Cosmocil CQ™ available from Zeneca

PLC, preferably used at up to 1% and more preferably at 0.03% to 0.3% by weight; 2 ' , 4, 4 ' -trichloro, 2-hydroxy- diphenyl ether (triclosan) , preferably used at up to 1% by weight of the composition and more preferably at 0.05-0.3%; and 3, 7, ll-trimethyldodeca-2, 6, 10-trienol (farnesol) , preferably used at up to 1% by weight of the composition and more preferably at up to 0.5%.

Other suitable organic antimicrobial agents are transition metal chelators, as described in WO01/52805, for example. Transitional metal chelators having a binding coefficient for iron (III) of greater than 10 , for example diethylenetriaminepentaacetic acid and salts thereof are preferred.

The polypeptide may be applied to the surface of the human body by any means. Application of liquid compositions comprising the polypeptide can be by absorption onto a carrier matrix like paper, fabric, or sponge and application by contacting said carrier matrix with the surface. Application can also comprise a combination of any two or more of the above techniques.

Other components may also be present in compositions used in accordance with the present invention. Often, for example, water may be present in a composition comprising the polypeptide. In such compositions, the water may be considered as a carrier for the polypeptide. Other carrier materials may alternatively or additionally be employed, provided that they are cosmetically acceptable.

The other components used in compositions suitable for use in accordance with the invention will vary according to the desired mode of application of the composition. For example, a volatile propellant is a typical component in compositions for spray application and a liquid carrier fluid (usually water) is a typical component in compositions for roll-on application.

A liquid carrier fluid is a highly desirable additional component. Such materials act as solvents or carriers for the other components of the composition, facilitating their delivery. Water can be used as a carrier fluid, although it is more preferable to use mixtures of water and an alcohol, especially ethanol. Alcohol/water mixtures are particularly suitable carrier fluids in roll-on and pump spray products. Cyclomethicones and other volatile silicones are another class of carrier fluid that may be employed. Examples of this latter class are Dow Corning silicone fluids 344, 345, 244, 245, 246, 556, and the 200 series; Union Carbide Corp. silicones 2707 and 7158; and General Electric silicone SF1202. Alternatively, non-silicone hydrophobic liquids may be employed, such as mineral oils, hydrogenated polyisobutene, polydecene, paraffins, isoparaffins of at least 10 carbon atoms, and aliphatic and aromatic ester iols. Propylene glycol, butylene glycol, and related glycols may also be used. Other alternative carrier fluids include materials having multiple functions, for example isopropyl myristate, isopropyl palmitate, dipropylene glycol, and glycerol. Mixtures of carrier fluids may also be employed to advantage. Compositions preferably comprise carrier fluid at a level of from 30% to 98% by weight, or more preferably from 60% to 97% by weight, of the non- volatile components of the composition. Emulsifiers are further additional components of the compositions of the invention that are highly desirable in certain product forms. Emulsifiers are preferably present at from 0.1% to 10% by weight of the composition. Suitable emulsifiers include steareth-2, steareth-20, steareth-21, ceteareth-20, glyceryl stearate, cetyl alcohol, cetearyl alcohol, PEG-20 stearate, and dimethicone copolyol.

Further emulsifiers desirable in certain compositions of the invention are perfume solubilisers and wash-off agents.

Examples of the former include PEG-hydrogenated castor oil, available from BASF in the Cremaphor RH and CO ranges, preferably present at up to 1.5% by weight, more preferably 0.3 to 0.7% by weight. Examples of the latter include poly (oxyethylene) ethers.

Certain sensory modifiers are further desirable components. Such materials are preferably used at a level of up to 20% by weight of the composition. Emollients, humectants, volatile oils, non-volatile oils, and particulate solids which impart lubricity are all suitable classes of sensory modifiers. Examples of such materials include cyclomethicone, dimethicone, dimethiconol, sunflower seed oil, isopropyl myristate, isopropyl palmitate, talc, finely- divided silica (eg. Aerosil 200), particulate polyethylene (eg. Acumist B18), polysaccharides, corn starch, C12-C15 alkyl benzoate, PPG-3 myristyl ether, octyl dodecanol, Cl- C14 isoparaffins, di-isopropyl adipate, isosorbide laurate, PPG-14 butyl ether, glycerol, hydrogenated polyisobutene, polydecene, titanium dioxide, phenyl trimethicone, dioctyl adipate, and hexamethyl disiloxane. Fragrance is also a desirable additional component. Suitable materials include conventional perfumes, such as perfume oils and also include so-called deo-perfumes, as described in EP 545,556 and other publications. Levels of incorporation are preferably up to 4% by weight, particularly from 0.1% to 2% by weight, and especially from 0.7% to 1.7% by weight.

It should be noted that certain components of compositions perform more than one function. Such components are particularly preferred additional ingredients, their use often saving both money and formulation space. Examples of such components include ethanol, isopropyl myristate, and the many components that can act as sensory modifiers.

Further additional components that may also be included are colourants and preservatives at a conventional concentration, for example C₁-C3 alkyl parabens .

Examples

In the following examples all percentages are by weight. With reference to the peptides and organic anti-microbials, they refer to the active ingredient per se.

The cosmetic compositions indicated in Table 1 may be prepared using methods known in the art. It will be noted that the compositions comprising both the peptide and an anti-microbial, can deliver both significant antiperspirancy and significant deodorancy. Table 1

1. GIu. GIu. Met . GIn . Arg. Arg. Ala . , ex Lipotec SA.

2. GIu. GIu. Met .GIn. Arg. Arg. Ala. Asp. , ex Lipotec SA.

3. 2 ' , 4 , 4 ' -trichloro, 2-hydroxy-diphenyl ether.

4. Polyhexamethylene biguanide salt.

Claims

1. A non-therapeutic method of reducing perspiration in the axilla comprising the application to the axilla of a polypeptide or derivative thereof comprising the amino acid sequence: GIu . GIu .Met . GIn . Arg. Arg. Ala .

2. A non-therapeutic method of reducing perspiration of the feet comprising the application to the feet of a polypeptide or derivative thereof comprising the amino acid sequence GIu . GIu .Met . GIn .Arg. Arg. Ala .

3. A method according to claim 1 or claim 2, comprising spray application.

4. A method according to claim 1 or claim 2, comprising application of the polypeptide from a roll-on composition comprising water.

5. A method according to any of the preceding claims, comprising the application of a further polypeptide comprising the amino acid sequence Tyr . Ala . GIy . Phe . Leu .

6. A method according to any of the preceding claims, comprising the application of a further peptide comprising the structure β-Ala-Pro- diaminobutyroylbenzylamide .

7. A method according to any of the preceding claims, comprising the application of a lamellar phase stabilised oil-in-water emulsion.

8. A cosmetic composition comprising a polypeptide or derivative thereof comprising the amino acid sequence: GIu . GIu .Met . GIn . Arg. Arg. Ala . and an astringent salt of aluminium and/or zirconium.

9. A cosmetic composition comprising a polypeptide or derivative thereof comprising the amino acid sequence GIu . GIu .Met . GIn .Arg .Arg .Ala . and an anti-microbial deodorant agent.

10. A cosmetic composition comprising a polypeptide or derivative thereof comprising the amino acid sequence GIu . GIu .Met . GIn .Arg. Arg. Ala . and lamellar phase stabilised oil-in-water emulsion.

11. A method of controlling perspiration comprising the application to the surface of the human body of a composition according to any of claims 8 to 10.

12. The use of a polypeptide or derivative thereof comprising the amino acid sequence:

GIu . GIu .Met . GIn .Arg. Arg. Ala . for the manufacture of a medicament for the treatment of sweating.