EP1227790A1

EP1227790A1 - Cosmetic compositions

Info

Publication number: EP1227790A1
Application number: EP00961833A
Authority: EP
Inventors: Robert Francis Date; Lisa Catherine Duffy; Christopher John Bullion; Emma Kate Brown
Original assignee: Procter and Gamble Co
Current assignee: Procter and Gamble Co
Priority date: 1999-11-08
Filing date: 2000-09-13
Publication date: 2002-08-07
Also published as: WO2001034111A1; JP2003520205A; CN1420760A; MXPA02004613A; AU7373000A; IE990935A1

Abstract

A cosmetic composition suitable for topical application to the skin or hair comprising: (a) a protease enzyme, or mixtures thereof; and (b) from about 2 % to about 45 % by weight of an emulsifier which is capable of forming liquid crystals in water and comprises a mixture of at least one emulsifier having a high HLB and at least one emulsifier having a low HLB, with a melting point of at least 45 °C, the ratio of low HLB emulsifier to high HLB emulsifier being from about 10:1 to about 100:1. The compositions of the invention display high enzyme stability, and the products comprising same have high moisturisation efficacy, as well as good rheological and absorption properties, in addition to skin feel, skin softness and skin smoothness benefits.

Description

Cosmetic Compositions

Technical Field

The present invention relates to cosmetic compositions. In particular it relates to stable cosmetic compositions comprising a protease enzyme, or mixtures thereof; and to cosmetic products comprising the compositions. The compositions display good enzyme stability while the cosmetic products have excellent skin softness, and skin smoothness benefits.

Background of the Invention

Skin is made up of several layers of cells which coat and protect the keratin and collagen fibrous proteins that form the skeleton of its structure. The outermost of these layers, referred to as the stratum corneum, is known to be composed of 25nm protein bundles surrounded by 8nm thick layers. Anionic surfactants and organic solvents typically penetrate the stratum corneum membrane and, by delipidization (i.e. removal of the lipids from the stratum corneum), destroy its integrity. This destruction of the skin surface topography leads to a rough feel and may eventually permit the surfactant or solvent to interact with the keratin, creating irritation.

Dry, itchy or flaky skin may also result from the failure to maintain a proper water gradient across the stratum corneum. Most of the water needed to maintain the water gradient, which is sometimes considered to be the stratum corneum's plasticizer, comes from inside the body. If the humidity is too low, such as in a cold climate, insufficient water remains in the outer layers of the stratum corneum to properly plasticize the tissue, and the skin begins to scale and becomes itchy.

The use of protease enzymes in cosmetic compositions to provide a skin care benefit is known. It is believed that protease enzymes function primarily by providing a desquamatory action to the cosmetic composition. It is believed that the proteases remove damaged (e.g. dry) skin cells on the surface of the skin, thereby reducing the rough feel associated therewith. The protease removes the effect of prior damage to the skin, giving the skin a fresher, more youthful appearance and feel. However, protease enzymes have the disadvantage of being readily degraded (i.e. they undergo auto lysis) in conventional cosmetic compositions because of the presence of water. Various attempts have been made to stabilise enzymes in cosmetic compositions. Some of these involve increasing the polyol level in order to reduce the water activity value of the composition. See for example EP-A-759293, EP-A-755672 and EP-A-779071. Other attempts to stabilise the enzyme in cosmetic compositions involve its encapsulation. See for example US-A- 5811112 and WO98/48775.

Although previous attempts to stabilise enzymes in cosmetic compositions have met with varying degrees of success, there remains a need for compositions in which the enzymes incorporated therein are stabilised to a high degree. While previous art teaches methods of stabilising enzymes in products, this invention by comparison, in addition to identifying a novel stabilisation approach, also details a method of activating the enzyme during its intended use.

It has now been unexpectedly found that by incorporating an emulsifier capable of forming liquid crystals in water into a cosmetic composition comprising efficacious levels of a protease enzyme, a composition is provided in which the enzyme is stabilised to a high degree. Cosmetic products comprising the compositions herein show good absorption, and water retention properties, in addition to skin softness and skin smoothness benefits and excellent moisturisation characteristics. Emulsifiers capable of forming liquid crystals in water are known for use in cosmetic compositions. See for example WO97/32560, WO97/32561 and WO/94/17830, and brochures from ICI Surfactants: (1) 'Arlatone ' 2121: Natural emulsifier for oil-in-water milks and creams (Ref. 41-5E); and (2) Ethylene-oxide-free oil-in-water and water-in-oil (W/O) emulsifiers by Dederen, C. et al. (Ref. RP72/92E). However, none of these documents teaches or suggests the use of such emulsifiers for stabilising enzymes in cosmetic compositions.

Summary of the Invention

According to one aspect of the present invention there is provided a cosmetic composition suitable for topical application to the skin or hair comprising:

(a) a protease enzyme, or mixtures thereof;

(b) from about 2% to about 45% by weight of an emulsifier which is capable of forming liquid crystals in water and comprises a mixture of at least one emulsifier having a high HLB and at least one emulsifier having a low HLB with a melting point of at least 45°C, the ratio of low HLB emulsifier to high HLB emulsifier being from about 10 : 1 to about 100 : 1; and

(c) a topical carrier.

According to a second aspect of the present invention there is provided a cosmetic product comprising (I) a cosmetic composition suitable for topical application to the skin comprising (a) a protease enzyme, or mixtures thereof; (b) from about 2% to about 45% by weight of an emulsifier which is capable of forming liquid crystals in water; and (c) a topical carrier; and (II) a moisturising composition consisting of water and/or comprising other excipients suitable for topical application to the skin having a water activity value > 0.85, preferably > 0.90, more preferably > 0.95 and most preferably > 0.97 and being capable of activating the protease enzyme, or mixtures thereof of component (I), the components (I) and (II) being separately presented for simultaneous or sequential application. Additionally, components (I) and (II) may be mixed prior to application.

In a preferred embodiment, the emulsifier of component (I) of the cosmetic products herein preferably comprises a mixture of at least one emulsifier having a high HLB and at least one emulsifier having a low HLB with a melting point of at least 45 °C, the ratio of low HLB to high HLB emulsifier being from about 10 : 1 to about 100 : 1.

The cosmetic products of this invention display high moisturisation efficacy, as well as good Theological and absorption properties, in addition to skin softness and skin smoothness benefits. The cosmetic products herein make possible the activation of the enzyme during its intended use, the enzyme being activated upon contact with the moisturising composition.

According to a third aspect of the present invention there is provided a cosmetic method of treatment of the skin or hair comprising applying to the skin or hair a cosmetic product according to the present invention.

According to a fourth aspect of the present invention there is provided a use of an emulsifier capable of forming liquid crystals in water for stabilising a protease enzyme, or mixtures thereof, in a skin or hair care composition.

According to a fifth aspect of the present invention there is provided a use of a composition comprising a protease enzyme, or mixtures thereof; an emulsifier capable of forming liquid crystals in water; and a topical carrier; for a skin or hair care application.

According to a sixth aspect of the present invention there is provided a cosmetic composition suitable for topical application to the skin or hair comprising:

(a) Protease F;

(b) from about 2% to about 45% by weight of an emulsifier which is capable of forming liquid crystals in water; and

(c) a topical carrier.

The emulsifier in the composition immediately above preferably comprises a mixture of at least one emulsifier having a high HLB and at least one emulsifier having a low HLB with a melting point of at least 45°C, the ratio of low HLB emulsifier to high HLB emulsifier being from about 10 : 1 to about 100 : 1.

Detailed Description of the Invention

The compositions of the present invention comprise a protease enzyme together with an essential emulsifier component and a topical carrier, as well as various optional ingredients as indicated below. It is to be understood that the moisturising composition of component II of the cosmetic products herein, in addition to containing water, may also contain any of the various optional ingredients described hereinbelow. All levels and ratios are by weight of total composition, unless otherwise indicated. Chain length and degrees of ethoxylation are also specified on a weight average basis.

The term "skin conditioning agent", as used herein means a material which is capable of providing a cosmetic conditioning benefit to the skin such as moisturization, humectancy (i.e. the ability to retain or hold water or moisture in the skin), emolliency, visual improvement of the skin surface, soothing of the skin, softening of the skin, and improvement in skin feel.

The term "enzyme" as used herein means the enzyme, wild-type or variant, either per se, or chemically modified by the conjugation of polymer moieties.

As used herein, the term "wild-type" refers to an enzyme produced by unmutated hosts.

As used herein, the term "variant", means an enzyme having an amino acid sequence which differs from that of the wild-type enzyme due to the genetic mutation of the host producing that enzyme.

The water activity a_w of a medium containing water is the ratio of the water vapour pressure of the product "P_H20 product" to the vapour pressure of pure water "P_H2O pure" at the same temperature. It can also be expressed as the ratio of the number of molecules of water "NH_2O" to the total number of molecules

"NH2₀ + Ndissoived substances", which takes account of the molecules of dissolved substances J dissolved substances • It is given by the following formulae:

^pH₂O ^{product N}H₂O

^pH₂O ^NH₂O + dissolved substances

Various methods can be used for measuring the water activity. The most common is the manometric method, by which the vapour presssure is measured directly.

The present compositions can be used for any suitable purpose. In particular, the present compositions are suitable for topical application to the skin or hair. In particular, the compositions can be in the form of creams, lotions, gels, and the like. Preferably the cosmetic compositions herein are in the form of an emulsion of one or more oil phases in an aqueous continuous phase.

Enzyme

An essential component of the present invention is a protease enzyme.

Protease enzymes are classified under the Enzyme Classification number E.C. 3.4

(Carboxylic Ester Hydrolases) in accordance with the Recommendations (1992) of the International Union of Biochemistry and Molecular Biology (IUBMB). Useful proteases are also described in PCT publications: WO 95/30010 published November 9, 1995 by The Procter & Gamble Company; WO 95/30011 published November 9, 1995 by The Procter & Gamble Company; WO 95/29979 published November 9, X 995 by The Procter & Gamble Company. Preferred protease enzymes for use herein are subtilisin, chymotrypsin and elastase-type protease enzymes.

Especially preferred for use herein are subtilisin-type protease enzymes. Subtilisin enzymes are naturally produced by Bacillus alcalophilus, Bacillus amyloliquefaciens, Bacillus amylosaccharicus, Bacillus licheniformis, Bacillus lentus and Bacillus subtilis microorganisms. A particularly preferred substilisin-type enzyme is bacterial serine protease enzyme, and variants thereof, obtained from Bacillus amyloliquefaciens, Bacillus licheniformis and/or

Bacillus subtilis, including Novo Industries A/S Alcalase®, Esperase® , Savinase®

(Copenhagen, Denmark), Gist-brocades' Maxatase®, Maxacal® and Maxapem 15® (protein engineered Maxacal®) (Delft, Netherlands), and subtilisin BPN and BPN', which are commercially available.

Especially preferred are protease enzymes, and variants thereof, obtained from Bacillus amyloliquefaciens. One known enzyme is BPN'. The wild-type BPN' from Bacillus amyloliquefaciens is characterized by the amino acid sequence:

1 10 20

AlaGlnSer ValProTyrGlyVal SerGln He LysAlaPro AlaLeuHis SerGlnGly

30 40

TyrThrGlySerAsnValLysVal AlaVal He AspSerGly He AspSer Ser HisPro 50 60

AspLeuLysVal AlaGlyGlyAla SerMetValPro Ser GluThrAsnProPheGlnAsp

70 80

AsnAsnSerHisGlyThrHisValAlaGlyThrValAlaAlaLeuAsnAsnSerlle Gly

90 100 ValLeuGly Val AlaPro Ser Ala SerLeuTyr Ala ValLys ValLeuGlyAlaAspGly

110 120

SerGlyGlnTyr SerTrp He He AsnGly He GluTrpAla He AlaAsnAsnMetAsp

130 140

Val He AsnMetSerLeuGlyGlyPro SerGlySerAlaAlaLeuLysAlaAlaValAsp 150 160 LysAlaValAlaSerGlyValValValValAlaAlaAlaGlyAsnGluGlyThrSerGly

170 180

SerSer SerThrValGlyTyrProGlyLysTyrPro SerVal He AlaVal GlyAla Val

190 200 AspSer SerAsnGlnArgAlaSerPheSer SerValGlyProGluLeuAspValMetAla

210 220

Pro Gly Val Ser He GlnSerThrLeuProGlyAsnLysTyrGlyAlaTyrAsnGlyThr

230 240

SerMetAlaSerProHisValAlaGlyAlaAlaAlaLeu He LeuSerLysHisProAsn 250 260

TrpThrAsnThrGlnValArgSerSerLeuGluAsnThrThrThrLysLeuGlyAspSer

270 275

PheTyrTyrGlyLysLysGlyLeu He AsnAsnValGlnAlaAlaAlaGln

Variants of BPN', hereafter referred to as "Protease A", are disclosed in U.S. Patent 5,030,378 (issued to Venegas, July 9, 1991) as characterized by the BPN' amino acid sequence with the following mutations:

a.) the Gly at position Glyl66 is replaced with Asn, Ser, Lys, Arg, His, Gin,

Ala or Glu; the Gly at position Gly 169 is replaced with Ser; the Met at position Met222 is replaced with Gin, Phe, Cys, His, Asn, Glu, Ala or Thr; or

b.) the Gly at position Gly 166 is replaced with Lys and the Met at position

Met222 is replaced with Cys; or

c.) the Gly at position Gly 160 is replaced with Ala and the Met at position

Met222 is replaced with Ala. Additional variants of BPN', heretoforth referred to as "Protease B", are disclosed by Genencor International, Inc. (San Francisco, California) European Patent EP-B-251 ,446 (granted December 28, 1994 and published January 7, 1988) as characterized by the wild- type BPN' amino acid with the mutations in one or more of the following amino acids: Tyr21, Thr22, Ser24, Asp36, Ala 45, Ala48, Ser49, Met50, His67, Ser87, Lys94, Val95, Gly97, SerlOl, Glyl02, Glyl03, Ilel07, Glyl 10, Met 124, Glyl27, Glyl28, Prol29, Leul35, Lysl70, Tyrl71, Prol72, Aspl97, Met 199, Ser 204, Lys213, Tyr214, Gly215, and Ser221; or two or more of the amino acids listed above and Asp32, Ser33, Tyrl04, Alal52, Asnl55, Glul56, Glyl 66, Glyl69, Phel89, Tyr217, and Met222 wherein both mutations cannot be made on the Asp32, Ser33, Tyrl04, Alal52, Asnl55, Glul56, Glyl 66, Glyl 69, Phel89, Tyr217, and Met222 amino acids.

Another preferred BPN' variant protease, hereafter referred to as "Protease D", is described in WO 95/10615 published April 20, 1995 by Genencor International as characterized by the wild-type BPN' amino acid with mutation to position Asn76, in combination with mutations in one or more other amino acid positions selected from the group consisting of Asp99, SerlOl, Glnl03, Tyrl04, Serl05, Ilel07, Asnl09, Asnl23, Leul26, Glyl27, Glyl28, Leul35, Glul56, Glyl66, Glul95, Aspl97, Ser204, Gln206, Pro210, Ala216, Tyr217, Asn218, Met222, Ser260, Lys265, and or Ala274.

Another preferred BPN' variant protease, hereafter referred to as "Protease F", is described in U.S. Patent Number 4,760,025, issued to Estell, et al. on July 26, 1988 as characterized by the wild-type BPN' amino acid with mutation to one or more amino acid positions selected from the group consisting of Asp32, Ser33, His64, Tyrl04, Asnl55, Glul56, Glyl 66, Glyl 69, Phel89, Tyr217, and Met222.

Preferred proteolytic enzymes, then, are selected from the group consisting of Alcalase®, BPN', Protease A, Protease B, Protease D, and Protease F, and mixtures thereof. Protease F is most preferred.

Also suitable for use herein are proteases which are designed to maintain high levels of activity whilst at the same time diminish potential allergenic responses. Example of such proteases include chemically modified proteases such as those described in WO99/06071 wherein protease molecules are modified with a plurality of twin polymer moieties conjugated to the protease, and those described in co-pending US Application No. 09/088912 filed on June 8, 1998 by The Procter and Gamble Company.

Further suitable examples of proteases designed to display reduced allergenicity, yet maintain high activity, are protease molecules whose epitope regions have been mapped and subsequently altered by removing, changing, or masking regions of the epitope amino acid sequence. Epitope regions are those active amino acid regions of the protease which are believed to invoke an allergic response. Suitable examples of such protease variants useful herein include those described in copending US Application Nos. 60/079447, filed March 26, 1998 and 60/079397, filed March 26, 1998 by The Procter and Gamble Company, herein both incorporated by reference.

The enzyme is preferably present at a level of from about 0.0001% to about 5%, more preferably from about 0.0005% to about 1%, and especially from about 0.001% to about 0.1 % by weight of the composition.

Emulsifier

As a second essential component, the compositions herein comprise an emulsifier which is capable of forming liquid crystals in water. It is not essential that the composition herein comprises liquid crystals at ambient temperature. Gel networks are commonly formed from liquid crystals as a result of cooling during the manufacturing procedure. It has been found that compositions that form gel networks at ambient temperature give excellent results.

In the literature, liquid crystals are also referred to as anisotropic fluids, a fourth state of matter, surfactant association structure or mesophases. Those terms are often used interchangeably. The term "lytropic" means a liquid crystalline system containing a polar solvent, such as water. The liquid crystals used herein are lamellar, hexagonal, or rod structures or mixtures thereof.

The liquid crystalline phase utilised in the compositions of the invention can be identified in various ways. A liquid crystal phase flows under shear and is characterised by a viscosity that is significantly different from the viscosity of its isotropic solution phase.

Also, when viewed with a polarised light microscope, liquid crystals or the gel networks formed at ambient temperature show identifiable birefringence, as, for example, plain lamellar birefringence, whereas when isotropic solutions and rigid gels are viewed under polarised light, both show dark fields.

Other suitable means for identifying liquid crystals include x-ray diffraction, NMR spectroscopy and transmission electron microscopy.

In the compositions herein, the emulsifier is a mixture comprising at least one emulsifier having a high HLB (hyrophilic lipophilic balance), and at least one emulsifier having a low HLB. The HLB system is well known in the art and is described in detail in "The HLB System, a Time-Saving Guide to Emulsifier Selection", ICI Americas Inc., August 1984, which is incorporated herein by reference. The ratio of low HLB emulsifier to high HLB emulsifier in the mixture is from about 10 : 1 to about 100 : 1. The emulsifier is incorporated into the composition in an amount of from about 2% to about 45%, preferably from about 3% to about 40%, more preferably from about 3% to about 30%, by weight of the composition.

Low HLB emulsifiers suitable for the present invention have an HLB of 1 to 8 and a melting point of at least 45°C. Examples of suitable low HLB emulsifiers for use in the compositions of this invention include the following: saturated C₁₆ to C₃₀ fatty alcohols, such as cetyl, stearyl and behenyl alcohols; saturated C₁₆ to C₃₀ hydroxy fatty acids, such as palmitic, stearic, behenic and hydroxystearic acids; Cg to C₂₄ mono- or polyglycerol esters, such as triglycerol stearate and triglycerol distearate; C₈ to C₂₄ polyol mono-, di- or tri-fatty acid esters such as sorbitan stearate, available under the trade name Arlacel 60 from ICI, Wilton, Middlesborough, U.K., sorbitan tristearate, available under the trade name Arlacel 65 from ICI, methyl glucose sequisterate, available under the trade name Glucate SS from Amerchol, Edison, New Jersey, U.S.A., and polyglycerol-3 -methyl glucose distearate, available under the trade name Tegocare 450 from Goldschmidt, Hopewell, Virginia, U.S.A., sucrose dipalmitate, sucrose distearate and dextrin palmitate; C₈ to C₃₀ glyceryl esters, such as glyceryl monostearate or distearate (40 - 60% mono), glyceryl monostearate, palmitate or laurate (90% mono) and glyceryl hydroxystearate; and saturated Cι₆ to C₃₀ ethoxylated fatty alcohols containing from about 1 to about 5 moles of ethylene oxide, such as steareth 2, available under the trade name Brij 72 from ICI, ceteth 2, available under the trade name Brij 52 from ICI, and beheneth 5 available under the trade name Nikkol BB-5 from Nikko Chemical Co., Ltd, Tokyo, Japan; and mixtures thereof.

The low HLB emulsifiers useful herein are selected from the group consisting of saturated C₁₆ to C ₀ fatty alcohols; saturated Cι₆ to C₃₀ ethoxylated fatty alcohols containing from about 1 to about 5 moles of ethylene oxide; C₈ to C₂₄ mono or polyglycerol esters; C₈ to C₂₄ polyol mono-, di-, or tri-fatty acid esters, wherein the polyol is preferably selected from dextrin, sugars, or sorbitan; saturated C)₆ to C₃₀ hydroxy fatty acids; and mixtures thereof.

Preferred low HLB emulsifiers for use herein include C₈ to C₂₄ polyol mono-fatty acid esters wherein the polyol is sorbitan; saturated C₁₆ to C₃₀ fatty alcohols; saturated C₁₆ to C₃₀ ethoxylated fatty alcohols and mixtures thereof. C₈ to C₂₄ sorbitan fatty acid esters are more preferred. Most preferred are glyceryl monostearate, stearyl alcohol, sorbitan stearate, cetyl alcohol, or mixtures thereof. A particularly preferred low HLB emulsifier is sorbitan stearate. High HLB emulsifiers have an HLB greater than 8. Suitable high HLB emulsifiers useful herein are cationic, anionic or nonionic. Preferred are nonionic. Suitable examples of nonionic high HLB emulsifiers include the following: alkoxylated ethers of Ci - C ₀ fatty alcohols, such as Steareth 10, available under the trade name Brij 76 from ICI, Wilton, Middlesborough, U.K., Steareth 20, available under the trade name Brij 78 from ICI, Steareth 21, available under the trade name Brij 721 from ICI, Steareth 100, available under the trade name Brij 700 from ICI, and Ceteareth -12, available under the trade name Emulgin Bl from Henkel, La Grange, Illinois, U.S.A.; alkoxylated derivatives of Ci - C₃₀ fatty acids, such as PEG-20-stearate, available under the trade name Myrj 49 from ICI, PEG-40-stearate, available under the trade name Myrj 52 from ICI, and PEG-lOO-stearate, available under the trade name Myrj 59 from ICI; alkyl polyoxyalkylene sugar esters, such as polysorbate 60, available under the trade name Tween 60 from ICI, PEG-20- methyl glucose sesquistearate, available under the trade name Glucamate SSE 20 from Amerchol, Edison, New Jersey, U.S.A., and PEG-20-glyceryl monostearate, available under the trade name Tagat S2 from Goldschmidt, Hopewell, Virginia, U.S.A.; mono-, di- or tri- sucrose fatty acid esters, preferably sucrose mono-fatty acid esters, such as sucrose cocoate, available under the trade name Crodesta SL-40 from Croda Surfactants, Goole, England, sucrose palmitate, available under the trade name Ryoto Sugar Ester P- 1570 from Mitsubishi-Kasei, Tokyo, Japan, and sucrose stearate, available under the trade name Crodesta F-160 from Croda Surfactants; polyglyceryl esters of Ci - C₃₀ fatty acids, such as decaglyceryl mono- or di- stearate; and Ci - C₃₀ ethers of polyols, such as cetearyl glucoside; and mixtures thereof.

Suitable anionic high HLB emulsifiers useful herein include lactates, such as sodium stearoyl lactylate, available from Nikko Chemical Co., Ltd; phosphonic acid esters and salts, such as diethanolamine cetyl phosphate, available under the trade name Amphisol from Givaudan-Roure, Clifton, New Jersey, U.S.A., and potassium cetyl phosphate, available under the trade name Amphisol K from Nikko Chemical Co., Ltd; and sulphuric acid esters, such as sodium cocomonoglyceride sulphate, available from Nikko Chemical Co., Ltd; and mixtures thereof. Suitable cationic high HLB emulsifiers useful herein include tetra-alkyl ammonium salts, such as dicetyl or distearyl dimethyl ammonium chloride, available from Witco, Greenwich, Connecticut, U.S.A.; and fatty acid amides, such as steapyrium chloride, available from Witco; and mixtures thereof.

Preferred high HLB emulsifiers for use herein are C]-C ₀ ethers of polyols; alkoxylated ethers of C]-C ₀ fatty alcohols; or mono-, di- or tri- sucrose fatty acid esters; or mixtures thereof. In mixtures of mono-sucrose fatty acid ester with di- or tri- sucrose esters, the monoester preferably comprises at least 70%, more preferably 80%, by weight of total sucrose ester mixture. Most preferred high HLB emulsifiers are mono-, di- or tri-sucrose fatty acid esters. A particularly preferred high HLB emulsifier is sucrose cocoate.

An emulsifier for use herein is most preferably a fatty acid ester blend based on a mixture of sorbitan fatty acid ester and sucrose fatty acid ester, especially a blend of sorbiton stearate and sucrose cocoate. This is commercially available from ICI under the trade name Arlatone 2121.

Carrier The compositions of the present invention comprise a safe and effective amount of a dermatologically acceptable carrier, suitable for topical application to the skin or hair within which the essential materials and optional other materials are incorporated to enable the essential materials and optional components to be delivered to the skin or hair at an appropriate concentration. The carrier can thus act as a diluent, dispersant, solvent, or the like for the protease enzyme(s) and the emulsifier component which ensures that they can be applied to and distributed evenly over the selected target at an appropriate concentration.

The carrier can be solid, semi-solid or liquid. Highly preferred carriers are liquid or semi- solid, such as creams, lotions and gels. Preferably the carrier is in the form of a lotion, cream or a gel, more preferably one which has a sufficient thickness or yield point to prevent the particles from sedimenting. The carrier can itself be inert or it can possess dermatological benefits of its own. The carrier should also be physically and chemically compatible with the essential components described herein, and should not unduly impair stability, efficacy or other use benefits associated with the compositions of the present invention.

The type of carrier ultilised in the present invention depends on the type of product form desired for the composition. The topical compositions useful in the subject invention may be made into a wide variety of product forms such as are known in the art. These include, but are not limited to, lotions, creams, gels, sticks, ointments, and pastes. These product forms may comprise several types of carriers including, but not limited to, solutions, emulsions, and gels.

Preferred carriers contain a dermatologically acceptable, hydrophilic diluent. Suitable hydrophilic diluents include water, organic hydrophilic diluents such as Ci - C₄ monohydric alcohols and low molecular weight glycols and polyols, including propylene glycol, polyethylene glycol (e.g. of MW 200-600), polypropylene glycol (e.g. of MW 425- 2025), glycerol, butylene glycol, 1,2,4-butanetriol, sorbitol esters, 1,2,6-hexametriol, ethanol, iso-propanol, sorbitol esters, ethoxylated ethers, propoxylated ethers and combinations thereof. The diluent is preferably liquid. Water is an especially preferred diluent. The composition preferably comprises at least about 20% of the hydrophilic diluent.

Preferred carriers comprise an emulsion comprising a hydrophilic phase, especially an aqueous phase, and a hydrophobic phase e.g., a lipid, oil or oily material. As well known to one skilled in the art, the hydrophilic phase will be dispersed in the hydrophobic phase, or vice versa, to form respectively hydrophilic or hydrophobic dispersed and continuous phases, depending on the composition ingredients. In emulsion technology, the term "dispersed phase" is a term well-known to one skilled in the art which means that the phase exists as small particles or droplets that are suspended in and surrounded by a continuous phase. The dispersed phase is also known as the internal or discontinuous phase. The emulsion may be or comprise (e.g., in a triple or other multi-phase emulsion) an oil-in-water emulsion or a water-in-oil emulsion such as a water-in-silicone emulsion. Oil-in-water emulsions typically comprise from about 1% to about 60% (preferably about 1% to about 30%) of the dispersed hydrophobic phase and from about 1% to about 99% (preferably from about 40% to about 90%) of the continuous hydrophilic phase; water-in- oil emulsions typically comprise from about 1% to about 98% (preferably from about 40% to about 90%) of the dispersed hydrophilic phase and from about 1% to about 50% (preferably about 1% to about 30%) of the continuous hydrophobic phase. Preferred compositions herein are oil-in-water emulsions.

In a preferred embodiment, the compositions herein are incorporated in a cosmetic product comprising:

(I) a cosmetic composition suitable for topical application to the skin or hair comprising (a) a protease enzyme, or mixtures thereof; (b) from about 2% to about 45% by weight of an emulsifier which is capable of forming liquid crystals in water; and (c) a topical carrier; and

(XT) a moisturising composition consisting of water and or comprising other excipients suitable for topical application to the skin or hair having a water activity value > 0.85, preferably > 0.90, more preferably > 0.95 and most preferably > 0.97, and being capable of activating the protease enzyme, or mixtures thereof of component (I), the components (I) and (XT) being separately presented for simultaneous or sequential application.

The cosmetic products herein may be presented, for example, in a dual compartment container, two separate containers, or a kit comprising two containers, wherein instructions for use are also included.

Optional Ingredients

Polvhvdric Alcohols The compositions herein preferably additionally comprise at least one polyhydric alcohol in a concentration of from about 20% to about 80%, more preferably from about 20% to about 70%, and especially from about 25% to about 60% by weight of the polyhydric alcohol, or mixtures thereof.

Suitable polyhydric alcohols for use herein include polyalkylene glycols and more preferably alkylene polyols and their derivatives, including propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol and derivatives thereof, sorbitol, hydroxypropyl sorbitol, erythritol, threitol, pentaerythritol, xylitol, glucitol, mannitol, hexylene glycol, butylene glycol (e.g., 1,3-butylene glycol), hexane triol (e.g., 1,2,6- hexanetriol), trimethylol propane, neopentyl glycol, glycerine, ethoxylated glycerine and propoxylated glycerine.

Preferred polyhydric alcohols of the present invention are selected from glycerine, butylene glycol, propylene glycol, dipropylene glycol, polyethylene glycol and derivatives thereof, hexane triol, ethoxylated glycerine and propoxylated glycerine, or mixtures thereof.

Most preferred polyhydric alcohols for use in the present invention are glycerine, butylene glycol, or mixtures thereof.

When the compositions of the present invention include a polyhydric alcohol, the concentration of the combined polyhydric alcohol and emulsifier is in the range of from about 20% to about 99%, preferably about 20% to about 95% and especially about 25% to about 90% by weight of the composition.

Salts

In a preferred embodiment, the compositions of the present invention additionally comprise a salt selected from alkali metal and alkaline earth metal salts, and mixtures thereof, preferably sodium, calcium and magnesium salts, and mixtures thereof.

Especially preferred for use herein are calcium and magnesium salts. The compositions herein preferably comprise from about 50 ppm to about 400 ppm of the salt, based on the amount of metal ion.

Enzymes

In a further preferred embodiment, the compositions herein may comprise additional enzymes selected from lipases, phospholipases, glycosidases, lactoperoxidases and cellulases, and mixtures thereof.

Oil Phase

Optionally, the cosmetic compositions herein are in the form of an emulsion of one or more oil phases in an aqueous continuous phase, each oil phase comprises a single oily component or a mixture of oily components in miscible or homogeneous form. Different oil phases contain different materials or combinations of materials from each other. The total level of oil phase components in the compositions of the invention is typically from about 0% to about 60%, preferably from about 1% to about 30%, and more preferably from about 1% to about 10%.

Preferably, the oil phase components of the compositions herein comprise an emollient material or mixtures thereof, a polyol carboxylic acid ester and a silicone oil, or mixtures thereof.

In preferred embodiments, the oil phase preferably comprises additional oily components such as a natural or synthetic oils selected from mineral, vegetable, and animal oils, fats and waxes, and mixtures thereof. These oily components are present in an amount of from about 0.1% to about 15%, more preferably from about 1% to about 10% by weight of composition. Preferred for use herein are for example, hydrocarbons such as mineral oils or petrolatum. Further examples suitable for use herein are disclosed in WO98/22085. Emollient materials

The compositions of the present invention can comprise emollient materials selected from branched chain hydrocarbons having an weight average molecular weight of from about 100 to about 15,000, preferably from about 100 to 1000; compounds of formula I:

Formula I

wherein R* is selected from H or CH3, R^, R3 and R⁴ are independently selected from Ci -C20 straight chain or branched chain alkyl, and x is an integer of from 1-20; and compounds having the formula (II):

O R ⁵ C O R ⁶

Formula H

wherein R^ is selected from optionally hydroxy or Ci -C4 alkyl substituted benzyl and R5 is selected from C1-C20 branched or straight chain alkyl; and mixtures thereof.

Suitable branched chain hydrocarbons for use herein are selected from isododecane, isohexadecane, isoeicosane, isooctahexacontane, isohexapentacontahectane, isopentacontaoctactane, petrolatum, and mixtures thereof. Suitable for use herein are branched chain aliphatic hydrocarbons sold under the trade name Permethyl (RTM) and commercially available from Presperse Inc., P.O. Box 735, South Plainfield, N.J. 07080, U.S.A. Suitable ester emollient materials of Formula I above include, but are not limited to, methyl isostearate, isopropyl isostearate, isostearyl neopentanoate. isononyl isononanoate, isodecyl octanoate, isodecyl isononanoate, tridecyl isononanoate, myristyl octanoate, octyl pelargonate, octyl isononanoate, myristyl myristate, myristyl neopentanoate, myristyl octanoate, myristyl propionate, isopropyl myristate and mixtures thereof. Suitable ester emollient materials of Formula (H) include but are not limited to C 12- 15 alkyl benzoates.

Preferred emollients for use herein are isohexadecane, isooctacontane, petrolatum, isononyl isononanoate, isodecyl octanoate, isodecyl isononanoate, tridecyl isononanoate, myristyl octanoate, octyl isononanoate, myristyl myristate, methyl isostearate, isopropyl isostearate, C12-15 alkyl benzoates and mixtures thereof.

Particularly preferred emollients for use herein are isohexadecane, isononyl isononanoate, methyl isostearate, isopropyl isostearate, petrolatum, or mixtures thereof.

The emollient material is preferably present in the compositions at a level of from about 0.1% to about 10%, preferably from about 0.1% to about 8%, especially from about 0.5% to about 5% by weight of composition.

Polyol carboxylic acid ester

The compositions of the present invention may further comprise as an additional emollient, a polyol carboxylic acid ester.

The compositions of the present invention preferably comprise from about 0.01% to about 20%, more preferably from about 0.1% to about 15%, and especially from about 0.1% to about 10%) by weight of the polyol ester. The level of polyol ester by weight of the oil in the composition is preferably from about 1% to about 30%, more preferably from about 5% to about 20%. From the viewpoint of providing improved skin softness and smoothness benefits, the weight ratio of the carboxylic acid polyol ester to the emollient material is preferably in the range of from about 5:1 to about 1:5, more preferably in the range of from 2: 1 to about 1 :2. The preferred polyol polyesters useful in this invention are C1 -C30 mono- and polyesters of sugars and related materials. These esters are derived from a sugar or polyol moiety and one or more carboxylic acid moieties. Depending on the constituent acid and sugar, these esters can be in either liquid or solid form at room temperature. Examples include: glucose tetraoleate, the galactose tetraesters of oleic acid, the sorbitol tetraoleate, sucrose tetraoleate, sucrose pentaoleate, sucrose hexaoleate, sucrose heptaoleate, sucrose octaoleate, sorbitol hexaester in which the carboxylic acid ester moieties are palmitoleate and arachidate in a 1 :2 molar ratio, and the octaester of sucrose wherein the esterifying carboxylic acid moieties are laurate, linoleate and behenate in a 1 :3:4 molar ratio. Other materials include cottonseed oil or soybean oil fatty acid esters of sucrose. Other examples of such materials are described in WO 96/16636, incorporated by reference herein. A particularly preferred material is known by the HSTCI name sucrose polycottonseedate.

Silicone Oil

The present compositions preferably comprise, at least one silicone oil phase. Silicone oil phase(s) generally comprises from about 0.1% to about 20%, preferably from about 0.5% to about 10%, more preferably from about 0.5% to about 5%, of the composition. The, or each, silicone oil phase preferably comprises one or more silicone components.

Silicone components can be fluids, including straight chain, branched and cyclic silicones. Suitable silicone fluids useful herein include silicones inclusive of polyalkyl siloxane fluids, polyaryl siloxane fluids, cyclic and linear polyalkylsiloxanes, polyalkoxylated silicones, amino and quaternary ammonium modified silicones, polyalkylaryl siloxanes or a polyether siloxane copolymer and mixtures thereof. The silicone fluids can be volatile or non-volatile. Silicone fluids generally have a weight average molecular weight of less than about 200,000. Suitable silicone fluids have a molecular weight of about 100,000 or less, preferably about 50,000 or less, most preferably about 10,000 or less. Preferably the silicone fluid is selected from silicone fluids having a weight average molecular weight in the range from about 100 to about 50,000 and preferably from about 200 to about 40,000. Typically, silicone fluids have a viscosity ranging from about 0.65 to about 600,000 mm^.s'l, preferably from about 0.65 to about 10,000 mm^.s'l at 25°C. The viscosity can be measured by means of a glass capillary viscometer as set forth in Dow Corning Corporate Test Method CTM0004, July 29, 1970. Suitable polydimethyl siloxanes that can be used herein include those available, for example, from the General Electric Company as the SF and Viscasil (RTM) series and from Dow Corning as the Dow Corning 200 series. Also useful are essentially non-volatile polyalkylarylsiloxanes, for example, polymethylphenylsiloxanes, having viscosities of about 0.65 to 30,000 mm^.s"! at 25°C. These siloxanes are available, for example, from the General Electric Company as SF 1075 methyl phenyl fluid or from Dow Corning as 556 Cosmetic Grade Fluid. Cyclic polydimethylsiloxanes suitable for use herein are those having a ring structure incorporating from about 3 to about 7 (CH3)2SiO moieties.

In preferred embodiments, the silicone fluid is selected from dimethicone, decamethylcyclopentasiloxane, octamethylcyclotetrasiloxane, phenyl methicone, and mixtures thereof.

Silicone gums can also be used herein. The term "silicone gum" herein means high molecular weight silicones having a weight average molecular weight in excess of about 200,000 and preferably from about 200,000 to about 4,000,000. Iincluded are nonvolatile polyalkyl and polyaryl siloxane gums. In preferred embodiments, a silicone oil phase comprises a silicone gum or a mixture of silicones including the silicone gum. Typically, silicone gums have a viscosity at

25°C in excess of about 1,000,000 mm^s^'l . The silicone gums include dimethicones as described by Petrarch and others including US-A-4,152,416, May 1, 1979 to Spitzer, et al, and Noll, Walter, Chemistry and Technology of Silicones. New York: Academic Press 1968. Also describing silicone gums are General Electric Silicone Rubber Product Data Sheets SE 30, SE 33, SE 54 and SE 76. Specific examples of silicone gums include polydimethylsiloxane, (polydimethylsiloxane)(methylvinylsiloxane) copolymer, poly(dimethylsiloxane)(diphenyl)(methylvinylsiloxane) copolymer and mixtures thereof. Preferred silicone gums for use herein are silicone gums having a molecular weight of from about 200,000 to about 4,000,000 selected from dimethiconol, and dimethicone and mixtures thereof.

A silicone phase herein preferably comprises a silicone gum incorporated into the composition as part of a silicone gum-fluid blend. When the silicone gum is incorporated as part of a silicone gum-fluid blend, the silicone gum preferably constitutes from about 5% to about 40%, especially from about 10% to 20% by weight of the silicone gum-fluid blend. Suitable silicone gum-fluid blends herein are mixtures consisting essentially of:

(i) a silicone having a molecular weight of from about 200,000 to about 4,000,000 selected from dimethiconol, fluorosilicone and dimethicone and mixtures thereof; and

(ii) a carrier which is a silicone fluid, the carrier having a viscosity from about 0.65 mm^.s'l to about 100 mm^.s"!,

wherein the ratio of i) to ii) is from about 10:90 to about 20:80 and wherein said silicone gum-based component has a final viscosity of from about 100 mm^.s"! to about 100,000 mm^.s"!, preferably from 500 mm^.s'l to about 10,000 mm^.s-!.

An especially preferred silicone-gum fluid blend based component for use in the compositions herein is a dimethiconol gum having a molecular weight of from about

200,000 to about 4,000,000 along with a silicone fluid carrier with a viscosity of about

0.65 to 100 mm^.s'l. An example of this silicone component is Dow Corning Q2-1403 (85% 5 mm²^^"1 Dimethicone Fluid/15% Dimethiconol) and Dow Corning Q2-1401 available from Dow Corning.

Further silicone components suitable for use in a silicone oil phase herein are crosshnked polyorganosiloxane polymers, optionally dispersed in a fluid carrier. In general, when present the crosshnked polyorganosiloxane polymers, together with its carrier (if present) comprises 0.1% to about 20%, preferably from about 0.5% to about 10%, more preferably from about 0.5% to about 5% of the composition. Such polymers comprise polyorganosiloxane polymers crosshnked by a crosslinking agent. Suitable crosslinking agents are disclosed in WO98/22085. Examples of suitable polyorganosiloxane polymers for use herein include methyl vinyl dimethicone, methyl vinyl diphenyl dimethicone and methyl vinyl phenyl methyl diphenyl dimethicone.

Specific commercially available crosshnked polyorganosiloxane polymers for use herein are silicone vinyl crosspolymer mixtures available under the tradename KSG supplied by Shinetsu Chemical Co., Ltd, for example KSG-15, KSG-16, KSG-17, KSG-18. These materials contain a combination of crosshnked polyorganosiloxane polymer and silicone fluid. Particularly preferred for use herein especially in combination with the organic amphiphilic emulsifier material is KSG-18. The assigned INCI names for KSG-15, KSG- 16, KSG-17 and KSG-18 are cyclomethicone dimethicone/vinyl dimethicone crosspolymer, dimethicone dimethicone/vinyl dimethicone crosspolymer, cyclomethicone dimethicone/vinyl dimethicone crosspolymer and phenyl trimethicone dimethicone/phenyl vinyl dimethicone crosspolymer, respectively.

Another class of silicone components suitable for use in a silicone oil phase herein includes polydiorganosiloxane-polyoxyalkylene copolymers containing at least one polydiorganosiloxane segment and at least one polyoxyalkylene segment. Suitable polydiorganosiloxane segments and copolymers thereof are disclosed in WO98/22085. Suitable polydiorganosiloxane-polyalkylene copolymers are available commercially under the tradenames Belsil (RTM) from Wacker-Chemie GmbH, Geschaftsbereich S, Postfach D-8000 Munich 22 and Abil (RTM) from Th. Goldschmidt Ltd., Tego House, Victoria Road, Ruislip, Middlesex, HA4 OYL, for example Belsil (RTM) 6031 and Abil (RTM) B88183. A particularly preferred copolymer fluid blend for use herein includes Dow Corning DC3225C which has the CTFA designation Dimethicone/Dimethicone copolyol.

Polymeric Thickening Agents

The compositions of the present invention can comprise at least one polymeric thickening agent.

The polymeric thickening agents useful herein preferably have a number average molecular weight of greater than 20,000, more preferably greater than 50,000 and especially greater than 100,000.

In general, the compositions of the present invention may comprise from about 0.01% to about 10%, preferably from about 0.1% to about 8% and most preferably from about 0.5%) to about 5% by weight of the composition of the polymeric thickening agent, or mixtures thereof.

Preferred polymer thickening agents for use herein include non-ionic thickening agents and anionic thickening agents, or mixtures thereof. Suitable non-ionic thickening agents include polyacrylamide polymers, crosshnked poly(N-vinylpyrrolidones), polysaccharides, natural or synthetic gums, polyvinylpyrrolidone, and polyvinylalcohol.

Suitable anionic thickening agents include acrylic acid/ethyl acrylate copolymers, carboxyvinyl polymers and crosshnked copolymers of alkyl vinyl ethers and maleic anhydride. Particularly preferred thickening agents for use herein are the non-ionic polyacrylamide polymers such as polyacrylamide and isoparaffin and laureth-7, available under the trade name Sepigel 305 from Seppic Corporation, and acrylic acid/ethyl acrylate copolymers and the carboxyvinyl polymers sold by the B.F. Goodrich Company under the trade mark of Carbopol resins, or mixtures thereof. Suitable Carbopol resins may be hydrophobically modified, and other suitable resins are described in WO98/22085, or mixtures thereof. Humectants

The compositions of the present invention may comprise additional humectants which are preferably present at a level of from about 0.01% to about 20%, more preferably from about 0.1%o to about 15% and especially from about 0.5% to about 15%.

Suitable additional humectants useful herein are sodium 2-pyrrolidone-5-carboxylate (NaPCA), guanidine; glycolic acid and glycolate salts (e.g. ammonium and quaternary alkyl ammonium); lactic acid and lactate salts (e.g. ammonium and quaternary alkyl ammonium); aloe vera in any of its variety of forms (e.g., aloe vera gel); hyaluronic acid and derivatives thereof (e.g., salt derivatives such as sodium hyaluronate); lactamide monoethanolamine; acetamide monoethanolamine; urea; panthenol and derivatives thereof; and mixtures thereof.

At least part (up to about 5% by weight of composition) of an additional humectant can be incorporated in the form of an admixture with a particulate cross-linked hydrophobic acrylate or methacrylate copolymer, itself preferably present in an amount of from about 0.1% to about 10%, which can be added either to the aqueous or disperse phase. This copolymer is particularly valuable for reducing shine and controlling oil while helping to provide effective moisturization benefits and is described in further detail by WO96/03964, incorporated herein by reference.

The above listed compounds may be incorporated singly or in combination. Preferred additional humectants are selected from urea, panthenol and mixtures thereof.

A wide variety of optional ingredients such as neutralising agents, perfumes, and colouring agents, can also be added to the compositions herein.

Neutralizing agents suitable for use in neutralizing acidic group containing hydrophilic gelling agents herein include sodium hydroxide, potassium hydroxide, ammonium hydroxide, monoethanolamine, diethanolamine, amino methyl propanol, tris-buffer and triethanolamine. The compositions of the invention are generally in emulsion form and are preferably formulated so as to have a product viscosity of at least about 4,000 mPa.s and preferably in the range from about 4,000 to about 1,000,000 mPa.s, more preferably from about 8,000 to about 350,000 mPa.s and especially from about 10,000 to about 250,000 mPa.s and even more especially from about 10,000 to about 150,000 mPa.s (25°C, neat, Brookfield RVT, T Spindle at 5 rpms and Heliopath Stand).

The compositions of the invention can also contain from about 0.01% to about 10%, preferably from about 0.1% to about 5% of a panthenol moisturizer. The panthenol moisturizer can be selected from D-panthenol ([R]-2,4-dihydroxy-N-[3-hydroxypropyl)]- 3,3-dimethylbutamide), DL-panthenol, calcium pantothenate, royal jelly, panthetine, pantotheine, panthenyl ethyl ether, pangamic acid, pyridoxin, pantoyl lactose and Vitamin B complex.

Other optional materials include keratolytic agents/desquamation agents such as salicylic acid; water-soluble or solubilizable preservatives preferably at a level of from about 0.1% to about 5%, such as Germall 115, methyl, ethyl, propyl and butyl esters of hydroxybenzoic acid, benzyl alcohol, DMDM hydantoin iodopropanyl butylcarbanate available under the trade name Glydant Plus from Lonza, EDTA, Euxyl (RTM) K400, Bromopol (2-bromo-2-nitropropane-l,3-diol) and phenoxypropanol; anti-bacterials such as Irgasan (RTM) and phenoxyethanol (preferably at levels of from 0.1% to about 5%); soluble or colloidally-soluble moisturising agents such as hylaronic acid and starch- grafted sodium polyacrylates such as Sanwet (RTM) IM-1000, IM-1500 and IM-2500 available from Celanese Superabsorbent Materials, Portsmith, VA, USA and described in USA-A-4,076,663; vitamins such as vitamin A, vitamin C, vitamin E and derivatives thereof and vitamin K; alpha and beta hydroxyacids; aloe vera; sphingosines and phytosphingosines, cholesterol; skin whitening agents; N-acetyl cysteine; colouring agents; antibacterial agents such as TCC/TCS, also known as triclosan and trichlorocarbon; perfumes and perfume solubilizers. Also useful herein are sunscreening agents. A wide variety of sunscreening agents are described in U.S. Patent No. 5,087,445, to Haffey et al., issued February 11, 1992; U.S. Patent No. 5,073,372, to Turner et al., issued December 17, 1991; U.S. Patent No. 5,073,371, to Turner et al. issued December 17, 1991; and Segarin, et al., at Chapter VIE, pages 189 et seq., of Cosmetics Science and Technology. Prefeπed among those sunscreens which are useful in the compositions of the invention are those selected from 2-ethylhexyl p-methoxycinnamate, 2-ethylhexyl N,N-dimethyl-p-aminobenzoate, p- aminobenzoic acid, 2-phenylbenzimidazole-5-sulfonic acid, octocrylene, oxybenzone, homomenthyl salicylate, octyl salicylate, 4,4'-methoxy-t-butyldibenzoylmethane, 4- isopropyl dibenzoylmethane, 3-benzylidene camphor, 3-(4-methylbenzylidene) camphor, titanium dioxide, zinc oxide, silica, iron oxide, Parsol MCX, Eusolex 6300, Octocrylene, Parsol 1789, and mixtures thereof. Still other useful sunscreens are those disclosed in U.S. Patent No. 4,937,370, to Sabatelli, issued June 26, 1990; and U.S. Patent No. 4,999,186, to Sabatelli et al., issued March 12, 1991.

Generally, the sunscreens can comprise from about 0.5% to about 20% of the compositions useful herein. Exact amounts will vary depending upon the sunscreen chosen and the desired Sun Protection Factor (SPF). SPF is a commonly used measure of photoprotection of a sunscreen against erythema. See Federal Register. Vol. 43, No. 166, pp. 38206-38269, August 25, 1978.

The compositions of the present invention can additionally comprise from about 0.1% to about 5% by weight of aluminium starch octenylsuccinate. Aluminium starch octenylsuccinate is the aluminium salt of the reaction product of octenylsuccinic anhydride with starch and is commercially available under the trade name from Dry Flo National Starch & Chemical Ltd. Dry Flo is useful herein from the viewpoint of skin feel and application characteristics.

Other optional materials herein include pigments which, where water-insoluble, contribute to and are included in the total level of oil phase ingredients. Pigments suitable for use in the compositions of the present invention can be organic and/or inorganic. Also included within the term pigment are materials having a low colour or lustre such as matte finishing agents, and also light scattering agents. Preferably the compositions of the present invention comprise particulate materials having a refractive index of from about 1.3 to about 1.7, the particulate materials being dispersed in the composition and having a median particle size of from about 2 to about 30 μm. Preferably the particulates useful herein have relatively narrow distributions, by which is meant that more than 50% of the particles fall within 3 μm either side of the respective median value. Also preferred is that more than 50%, preferably more than 60%, more preferably more than 70% of particles fall within the size ranges prescribed for the respective median values. Suitable particulate materials are organic or organosihcone and preferably organosihcone polymers. Prefeπed particles are free-flowing, solid, materials. By "solid" is meant that the particles are not hollow. The void at the centre of hollow particles can have an adverse effect on refractive index and

therefore the visual effects of the particles on either skin or the composition. Suitable organic particulate materials include those made of polymethylsilsesquioxane, referenced above, polyamide, polythene, polyacrylonitrile, polyacrylic acid, polymethacrylic acid, polystyrene, polytetrafluoroethylene (PTFE) and poly(vinylidene chloride). Copolymers derived from monomers of the aforementioned materials can also be used. Inorganic materials include silica and boron nitride. Representative commercially available examples of useful particulate materials herein are Tospearl® 145 which has a median particle size of about 4.5 μm and EA-209® from Kobo which is an ethylene / acrylic acid copolymer having a median particle size of about 10 μm, Nylon- 12 available under the trade name Orgasol 2002 from Elf Atochem, France, or mixtures thereof.

Further examples of suitable pigments are titanium dioxide, predispersed titanium dioxide from Kobo e.g. Kobo GWL75CAP, iron oxides, acyglutamate iron oxides, ultramarine blue, D&C dyes, carmine, and mixtures thereof. Depending upon the type of composition, a mixture of pigments will normally be used. The prefeπed pigments for use herein from the viewpoint of moisturisation, skin feel, skin appearance and emulsion compatibility are treated pigments. The pigments can be treated with compounds such as amino acids, silicones, lecithin and ester oils.

Vitamin B component

The compositions of the present invention can also comprise a safe and effective amount of a vitamin B3 compound. The compositions of the present invention preferably comprise from about 0.01% to about 50%, more preferably from about 0.1% to about 20%, even more preferably from about 0.5% to about 10%, and still more preferably from about 1% to about 8%, most preferably from about 1.5% to about 6%, of the vitamin B3 compound.

As used herein, "vitamin B3 compound" means a compound having the formula:

wherein R is - CONH2 (i.e., niacinamide), - COOH (i.e., nicotinic acid) or - CH2OH (i.e., nicotinyl alcohol); derivatives thereof; and salts of any of the foregoing. Exemplary derivatives of the foregoing vitamin B3 compounds include nicotinic acid esters, including non-vasodilating esters of nicotinic acid, nicotinyl amino acids, nicotinyl alcohol esters of carboxylic acids, nicotinic acid N-oxide and niacinamide N-oxide.

Suitable esters of nicotinic acid include nicotinic acid esters of Cj-C22_> preferably C\-

C\_β, more preferably Ci -Cg alcohols. The alcohols are suitably straight-chain or branched chain, cyclic or acyclic, saturated or unsaturated (including aromatic), and substituted or unsubstituted. The esters are preferably non-vasodilating. As used herein, "non-vasodilating" means that the ester does not commonly yield a visible flushing response after application to the skin in the subject compositions (the majority of the general population would not experience a visible flushing response, although such compounds may cause vasodilation not visible to the naked eye). Non-vasodilating esters of nicotinic acid include tocopherol nicotinate and inositol hexanicotinate; tocopherol nicotinate is prefeπed. A more complete description of vitamin B3 compounds is given in WO 98/22085.

Examples of the above vitamin B3 compounds are well known in the art and are commercially available from a number of sources, e.g., the Sigma Chemical Company (St. Louis, MO); ICN Biomedicals, Inc. (Irvin, CA) and Aldrich Chemical Company

(Milwaukee, WI). One or more vitamin B3 compounds may be used herein. Prefeπed vitamin B3 compounds are niacinamide and tocopherol nicotinate. Niacinamide is more preferred.

Retinoids In a prefeπed embodiment, the compositions of the present invention also contain a retinoid. The vitamin B3 compound and retinoid provide unexpected benefits in regulating skin condition, especially in therapeutically regulating signs of skin aging, more especially wrinkles, lines, and pores. Without intending to be bound or otherwise limited by theory, it is believed that the vitamin B3 compound increases the conversion of certain retinoids to trans-retinoic acid, which is believed to be the biologically active form of the retinoid, to provide synergistic regulation of skin condition (namely, increased conversion for retinol, retinol esters, and retinal). In addition, the vitamin B3 compound unexpectedly mitigates redness, inflammation, dermatitis and the like which may otherwise be associated with topical application of retinoid (often refeπed to, and hereinafter alternatively refeπed to as "retinoid dermatitis"). Furthermore, the combined vitamin B3 compound and retinoid tend to increase the amount and activity of thioredoxin, which tends to increase collagen expression levels via the protein AP-1. Therefore, the present invention enables reduced active levels, and therefore reduced potential for retinoid dermatitis, while retaining significant positive skin conditioning benefits. In addition, higher levels of retinoid may still be used to obtain greater skin conditioning efficacy, without undesirable retinoid dermatitis occurring.

As used herein, "retinoid" includes all natural and/or synthetic analogs of Vitamin A or retinol-like compounds which possess the biological activity of Vitamin A in the skin as well as the geometric isomers and stereoisomers of these compounds.

The retinoid is preferably retinol, retinol esters (e.g., C2 - C22 alkyl esters of retinol, including retinyl palmitate, retinyl acetate, retinyl proprionate), retinal, and/or retinoic acid (including all-trans retinoic acid and/or 13-cis-retinoic acid), more preferably retinoids other than retinoic acid. These compounds are well known in the art and are commercially available from a number of sources, e.g., Sigma Chemical Company (St. Louis, MO), and Boehringer Mannheim (Indianapolis, IN). Preferred retinoids are retinol, retinyl palmitate, retinyl acetate, retinyl proprionate, retinal and combinations thereof. More prefeπed are retinol and retinyl palmitate. The retinoid may be included as the substantially pure material, or as an extract obtained by suitable physical and/or chemical isolation from natural (e.g., plant) sources.

The compositions preferably contain from or about 0.005% to or about 2%, more preferably 0.01% to about 2% retinoid. Retinol is most preferably used in an amount of from or about 0.01% to or about 0.15%; retinol esters are most preferably used in an amount of from about 0.01% to about 2% (e.g., about 1%).

Suitably, the pH of the compositions herein is greater than 5, preferably greater than 5.25 and more preferably greater than 5.40, also preferably less than 9, more preferably less than 8 and even more preferably less than 7.

The cosmetic compositions herein preferably have a water activity < 0.85, more preferably < 0.75, and most preferably < 0.70.

The compositions of the invention are preferably in the form of a moisturising cream or lotion, which can be applied to the skin or hair. The invention is illustrated by the following examples.

Examples I to VIH

Example I H IH IV V VI VH

In^gredient %__. %_ %_ %_ % %_ % w/w w/w w w/w w/w w/w w/w

Arlatone 2121 ' 5 5 10 10 15 5 45

Glycerine 25 25 50 25 30 60 0

Petrolatum - 5.0 - 5 - 10 5

Sucrose - - - 1.5 - 2.0 1

Polycottonseedate

Isohexadecane - - - 0.5 -

PPG-15-Stearyl - - - - 1.0 -

Ether

Dimethicone 2.0 2.0 2.0 3.0 2.0 1.5 2.5

Gransil Gel² - - - 1.0 - -

DC 1403³ 1.0 1.0 - 1.0 2.0 - 1.0

Protease F 0.010 0.015 0.05 0.00 0.030 0.025 0.020

5

Calcium Chloride 0.042 0.042 0.083 0.08 0.083 0.083 0.083

3

Water, Minors qs to qs to qs to qs to qs to qs to qs to

100 100 100 100 100 100 100 1. Supplied by ICI Surfactants, PO Box 90, Wilton Centre, Middlesborough, Cleveland TS6 8JE, England.

2. Supplied by Grant Industries Inc., Elmwood Park, New Jersey, USA. (The gel comprises 74-83% (w/w) cyclomethicone (D5), 12 - 16% (w/w) polysilicone 11 and 12

-15% (w/w) petrolatum)

3. A blend of dimethicone and dimethiconol

The compositions are made as follows:

Heat the water to 80°C, add glycerine with mixing. Disperse the Arlatone 2121 into the water phase with mixing. Heat oil phase ingredients to 80°C. Add to water phase with mixing. Cool and add temperature-sensitive ingredients at 30°C. Blend the enzyme (Protease F) solution at 30°C or below to the batch.

The compositions display high enzyme stability, as well as good rheological and absorption properties, in addition to skin feel, skin softness and skin smoothness benefits.

Claims

1. A cosmetic composition suitable for topical application to the skin or hair comprising:

(a) a protease enzyme, or mixtures thereof;

(c) a topical carrier.

2. A composition according to claim 1 wherein the enzyme is selected from subtilisin, chymotrypsin and elastase-type protease enzymes.

3. A composition according to claim 2, wherein the enzyme is selected from bacterial serine protease enzyme, and variants thereof, obtained from Bacillus amyloliquefaciens, Bacillus licheniformis and/ 'or Bacillus subtilis, including Alcalase®, Esperase® ,

Savinase®, Maxatase®, Maxacal® and Maxapem 15® (protein engineered Maxacal®), and subtilisin BPN and BPN^*.

4. A composition according to claim 3, wherein the enxyme is selected from the group consisting of Alcalase®, BPN', Protease A, Protease B, Protease D, and Protease F, and mixtures thereof, Protease F being prefeπed.

5. A composition according to any of claims 1 to 4 wherein the high HLB emulsifier is selected from Cι-C₃₀ ethers of polyols; alkoxylated ethers of C C₃o fatty alcohols; and mono-, di- or tri- sucrose fatty acid esters; and mixtures thereof, preferably mono-, di- or tri-sucrose fatty acid esters; and the low HLB emulsifier is selected from C₈ to C₂₄ polyol mono-fatty acid esters wherein the polyol is sorbitan; saturated Cι₆ to C₃₀ fatty alcohols; saturated C₁₆ to C o ethoxylated fatty alcohols and mixtures thereof, preferably C₈ to C₂₄ sorbitan fatty acid esters, more preferably glyceryl monostearate, stearyl alcohol, sorbitan stearate or cetyl alcohol, or mixtures thereof.

6. A cosmetic composition suitable for topical application to the skin or hair comprising:

(a) Protease F;

(c) a topical carrier.

7. A composition according to claim 5 or 6 wherein the emulsifier is a fatty acid ester blend based on a mixture of sorbitan fatty acid ester and sucrose fatty acid ester.

8. A composition according to claim 6 or 7 wherein the emulsifier is a blend of sorbitan stearate and sucrose cocoate.

9. A composition according to any of claims 1 to 8 comprising from about 3% to about 40%, preferably from about 3% to about 30%, by weight of emulsifier.

10. A composition according to any of claims 1 to 9 comprising from about 0.0001% to about 5%, preferably from about 0.0005% to about 1 % and most preferably from about

0.001% to about 0.1%, by weight of enzyme.

11. A composition according to any of claims 1 to 10 additionally comprising a salt selected from alkali metal and alkaline earth metal salts, and mixtures thereof, in an amount of from about 50 ppm to about 400 ppm based on the metal ion.

12. A composition according to claim 11 wherein the salt is selected from sodium, calcium and magnesium salts, and mixtures thereof.

13. A composition according to any of claims 1 to 12 additionally comprising from about 20% to about 80% by weight of a polyhydric alcohol selected from glycerine, butylene glycol, propylene glycol, dipropylene glycol, polyethylene glycol and derivatives thereof, hexane triol, ethoxylated glycerine and propoxylated glycerine, and mixtures thereof.

14. A composition according to claim 13 wherein the polyhydric alcohol is selected from glycerine, butylene glycol, or mixtures thereof.

15. A cosmetic product comprising:

(I) a cosmetic composition suitable for topical application to the skin or hair comprising (a) a protease enzyme, or mixtures thereof; (b) from about 2% to about 45% by weight of an emulsifier which is capable of forming liquid crystals in water; and (c) a topical carrier; wherein the cosmetic composition preferably has a water activity < 0.85; and

16. A cosmetic product according to claim 15 wherein the emulsifier of component (I) comprises a mixture of at least one emulsifier having a high HLB and at least one emulsifier having a low HLB with a melting point of at least 45 °C, the ratio of low HLB to high HLB emulsifier being from about 10 : 1 to about 100 : 1.

17. A cosmetic product according to any of claims 15 or 16 wherein the cosmetic composition (I) has the features of any of claims 2 to 14.

18. A cosmetic product according to any of claims 15 to 17 wherein the components I and H are mixed prior to application.

19. Use of from about 2% to about 45% by weight of an emulsifier capable of forming liquid crystals in water, the emulsifier comprising a mixture of at least one emulsifier having a high HLB and at least one emulsifier having a low HLB with a melting point of at least 45°C, the ratio of low HLB emulsifier to high HLB emulsifier being from about 10 : 1 to about 100 : 1, for stabilizing a protease enzyme, or mixtures thereof in a cosmetic composition suitable for topical application to the skin or hair.

20. Use according to claim 19 wherein the cosmetic composition has the features of any of claims 2 to 14.

21. Cosmetic method of treatment of the skin or hair comprising applying to the skin or hair a cosmetic product according to any of claims 15 to 18.