Cosmetic Method for Treatment of Skin and/or Hair Field of the Invention The present invention relates to a cosmetic method for treating the skin and/or hair wherein the method comprises a treatment regimen comprising administering a daily sequence of one or more unit doses as a repeating cycle. More particularly, the invention relates to a cosmetic method for treating skin or hair which comprises administering, according to a defined regimen, firstly a cosmetic composition comprising a biologically active enzyme followed by a placebo composition. Even more particularly the invention relates to a cosmetic method for treating skin or hair comprising administering a cosmetic composition comprising a protease enzyme followed by administering a placebo composition which method leads to noticeable improvement in skin condition and which can significantly slow, and even reverse, the signs of ageing.

Background Recently, across many fields, there has been an increase in the use of biologically active materials such as enzymes, antibiotics, anti-inflammatories and the like. This increase has been especially prominent in the cosmetic field, in particular in topical compositions for the skin or hair, where these biologically active materials have the benefit of being highly efficacious when compared with other more traditional ingredients. Furthermore, in some cases, the use of biologically active materials is the only way to achieve certain cosmetic benefits, there being no equivalent traditional ingredient.

Various different enzymes are currently of particular interest as key biological actives in cosmetic compositions. Examples of such enzymes include proteases which can support or replace a-hydroxy acids in skin peeling preparations (JP-A-04027388) or which can provide desquamatory action for treatment of dry, itchy or flaky skin (EP-A-0710478); glutathion sulphydryl oxidase which can be used in hair-wave setting (JP-A-4005220); glycosidases which can enhance the process of skin desquamation (W093/19731) and transglutaminase which can aid the formation of a protective layer on skin, hair and nails (WO94/18945, JP-A-02204407). Several innovative approaches have been taken to formulating cosmetic compositions comprising these enzymes, which are in general unstable in traditional cosmetic formulations. These include use of a dual compartment pack (WO 97/27841), use of precursor actives (EP-A-710,478), addition of antioxidants in conjunction with hydrophilic polyols (US-A-4,243,543) and the like.

As for any cosmetic material, these biologically active enzymes need to undergo rigorous safety testing prior to broad scale use. However, it is known that such highly efficacious biologically active enzymes can produce side effects, in the case of over exposure.

As such it would be useful to be able to develop a cosmetic method of treatment which enables the manufacturer to carefully metre the dose of biologically active enzyme thus minimising consumer risk. Furthermore it would be useful to further develop a cosmetic method which consists of a repeating treatment cycle, or regimen, wherein the user cycles between biologically active enzyme and placebo compositions such that exposure to the biologically active enzyme is controlled within a single treatment cycle. More particularly it would be highly preferred to be able to develop a kit, or single pack, which automatically cycles between delivering a biologically active enzyme and then a placebo composition, such that the consumer is unaware of the change from biologically active enzyme to placebo compositions and vice versa. Such a dispensing system would enable a manufacturer to exercise a high degree of control of exposure to the biologically active enzyme within a cycle and minimise the risk of a consumer continuing to over treat with the enzyme.

Prior art which related to cosmetic compositions comprising biologically active enzymes does not teach how to control consumer exposure to such biological actives. However, cyclic active/placebo treatment routines are known in the art, especially with respect to oral doses of pharmaceuticals. Examples include the female oral contraceptive pill (US5858405), treatment of menopausal symptoms (US4,425,339), polyphosphonate kits for treating osteoporosis (EP0210728) among other conditions. Part of the success of such treatment regimens has been in recognising that, for long term treatment, user compliance is greatly improved if a daily dosing routine can be introduced, even if this routine includes placebo. However, the art does not sufficiently teach how to apply these treatment routines to cosmetic compositions, particularly to cosmetic compositions for topical application to large areas of the skin or hair.

It has now been unexpectedly found that by developing a cosmetic method for treating skin or hair which comprises administering, according to a defined regimen, firstly a cosmetic composition comprising a biologically active enzyme followed by a placebo composition user compliance can be improved. This invention can be further enhanced by using a dual chamber dispensing system wherein the first chamber comprises a cosmetic composition comprising a biologically active enzyme and the second chamber comprises a placebo composition and wherein the dispensing system cycles between dispensing the two compositions according to the treatment method. It is believed that by exposing consumers to cosmetic compositions comprising biologically active compounds as part of a cyclic active/placebo treatment method, exposure of the biologically active compounds can be controlled such that the risks of over exposure are minimised. In addition, by developing this into a daily regimen, increased compliance can be achieved.

The risk of misuse/over-exposure is even further reduced by combining both biologically active enzyme and placebo compositions into a single dispensing system. Furthermore, if from a single dispensing system the consumer is unaware of the cyclic nature of the treatment method then the risk of non-compliance is reduced still further.

It is an object of the present invention to develop a cosmetic method of treating skin or hair which improves the condition of the skin or hair while minimising consumer exposure to the biologically active enzyme.

This, and other objects of this invention, will become apparent in light of the following disclosure.

Summary of the Invention The present invention relates to a cosmetic method for treating the skin and/or hair wherein the method comprises a treatment regimen comprising one or more cycles wherein a single cycle comprises: (a) administering, as phase one, for a period of 1 to 365 days, one or more unit doses a primary topical cosmetic composition comprising a biologically active enzyme, said enzyme being stably formulated; followed by (b) administering, as phase 2, for a period of 1 to 365 days, one or more unit doses of a placebo topical cosmetic composition.

This cosmetic treatment method is useful for enabling the manufacturer to control the level of consumer exposure to a biologically active compound and also for cosmetically treating the skin or hair to provide softness and smoothness benefits.

This invention further relates to a kit for use in the cosmetic method above, wherein the kit is characterised in that it contains the following components: (a) from about 1 to about 365 daily doses of a treatment composition comprising a biologically active compound, said biologically active compound being stably formulated; (b) from about 1 to about 365 daily doses of a placebo composition; (c) usage instructions directing the user as to how to use the two compositions in the cosmetic method.

Detailed Description of the Invention All percentages and ratios used herein are by weight of the total composition and all measurements made are at 25°C, unless otherwise designated. Unless otherwise indicated all percentages, ratios and levels of ingredients referred to herein are based on the actual amount of the ingredient, and do not include solvent, fillers or other materials which may be combined with the ingredient in commercially available products. Chain length and degrees of ethoxylation are also specified on a weight average basis.

All publications cited herein are hereby incorporated by reference in their entirety, unless otherwise indicated.

The term"biologically active enzyme"as used herein means the enzyme, wild-type or variant, either per se, or chemically modified by the conjugation of polymer moieties which, at the given level, displays a significant biological, therapeutic or pharmacological benefit.

The term"protease enzyme"as used herein refers to any enzyme whose substrate is a protein.

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.

As used herein"enzyme activity"refers to the activity of 201l1 of enzyme solution (50ppm) when reacted with the surface of a suitable proteinaceous substrate disc of diameter lcm, at room temperature over a 30 minute time period. By adjusting the pH of the enzyme buffer solution, it is possible to compare the effect of pH on enzyme activity.

For the enzymes for use herein suitable activity is defined as greater than 20% of reaction complete within 30minutes, preferably greater than 50%, more preferably greater than 75%. By using this measure it is defined that enzyme buffers of less than pH 5.5 are not suitable for use with this enzyme.

As used herein, the term"placebo"refers to a composition, including cosmetic compositions, which are essentially free from a biologically active enzyme wherein"free from"means that the biologically active enzyme is absent or present at such a low level that it does not deliver the desired end benefit. An example of such a low level would be that the final composition comprises less than 0.0001%, by weight, of a biologically active enzyme. However placebo compositions as defined herein may comprise many actives suitable for use on the skin and or hair including those which are known to those skilled in the art including skin care actives such as vitamin complexes, humectants, skin conditioning agents, sun screens and the like. Net the placebo composition can preferably be formulated such that it is designed to maintain the benefit of the biologically active enzyme throughout phase two of the treatment cycle.

The term"skin conditioning agent", as used herein means a material, excluding those materials which are defined as biologically active, 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 and improvement in skin feel.

The term"skin hydration"as used herein refers to an improvement in skin moisture content which can be determined either by technical measures such as by use of a corneometer etc, or expert visual measures for example Fitzpatrick skin dryness scale or by consumer self assessment.

The"water activity aw"of a medium containing water is the ratio of the water vapour pressure of the product"PH20 product"to the vapour pressure of pure water"PH20 pure"at the same temperature. It can also be expressed as the ratio of the number of molecules of water"NH20"to the total number of molecules: "NH2o + Ndissolved substances" which takes account of the molecules of dissolved substances Ndissolved substances- It is given by the following formulae: pH2Oproduct NH2O aw = = PH2O NH2O + Ndissolved substances Various methods can be used for measuring the water activity. The most common is the manometric method, by which the vapour pressure is measured directly.

The term"dermatologically-acceptable,"as used herein, means that the compositions, or components thereof, are suitable for use in contact with human skin without undue toxicity, incompatibility, instability, allergic response, and the like.

The term"safe and effective amount"as used herein means an amount of a compound, component, or composition sufficient to significantly induce a positive benefit, preferably a positive skin appearance. or feel benefit, including independently the benefits disclosed herein, but low enough to avoid serious side effects, i. e. to provide a reasonable benefit to risk ratio, within the scope of sound medical judgement.

Active and other ingredients useful herein may be categorised or described herein by their cosmetic and/or therapeutic benefit or their postulated mode of action. However, it is to be understood that the active and other ingredients useful herein can in some instances provide more than one cosmetic and/or therapeutic benefit or operate via more than one mode of action. Therefore, classifications herein are made for the sake of convenience and are not intended to limit an ingredient to the particularly stated application or applications listed.

The elements of these compositions are described in more detail below.

Cosmetic Metliod The present invention relates to a cosmetic method for treating the skin and/or hair wherein the method comprises a treatment regimen comprising one or more cycles wherein a single cycle comprises: (a) administering, as phase one, for a period of 1 to 365, preferably from 1 to 50, more preferably from 1 to 10, even more preferably from 1 to 7 and most preferably from 3 to 7 days one or more unit doses of a primary topical cosmetic composition comprising a biologically active enzyme, said enzyme being stably formulated; followed by (b) administering, as phase two, for a period of 1 to 365, preferably from 1 to 100, more preferably from 1 to 50, even more preferably from 10 to 40 and most preferably from 20 to 30 days one or more daily doses of a placebo composition.

The cosmetic method is further characterised in dosage cycle may be repeated for from about 1 to 1000 times, preferably from about 1 to 100 times, more preferably from about 1 to 12 times, even more preferably from about 1 to 6 times and most preferably from about 1 to 3 times in a single treatment period.

Furthermore each daily dosage sequence of the treatment cycle can comprise one or more unit doses. As such the cosmetic method, within a given day, may comprise administering on one, or several occasions throughout the day, either the cosmetic composition comprising the biologically active compound or the placebo composition as appropriate depending upon the phase of the treatment cycle. Furthermore on each treatment occasion the user may be advised to administer one or more metered or unmetered doses of the appropriate composition.

Furthermore, depending on the formulation of the biologically active enzyme comprising composition and the placebo composition it is preferred that phase one of the treatment regimen can comprise administering a placebo composition either simultaneously or sequentially with the cosmetic composition comprising the biologically active enzyme.

This dual administration of the cosmetic composition comprising the biologically active compound with the placebo composition during phase one of the treatment cycle extends the formulation possibilities of compositions suitable for use in the present invention and also allows for the dual administration of compounds which are not able to be formulated together within a single formulation.

Cosmetic Composition Comprising Biologically Active Compound - Essential Features The cosmetic method of the present invention comprises administering, through phase one of the treatment regimen cycle, one or more doses of a cosmetic composition comprising a biologically active enzyme, wherein the biologically active enzyme is stably formulated. Compositions useful herein comprise one or more enzymes selected from lipases, phospholipases, glycosidases, lactoperoxidases and cellulases, and mixtures thereof. Cosmetic compositions for use in phase one of the treatment method comprise from about 0.0001% to about 10%, more preferably from about 0.001% to about 5%, even more preferably from about 0.005% to about 1%, and most preferably from about 0.005% to about 0.5%, by weight, of the biologically active enzyme. Protease enzymes are the highly preferred biologically active compound for use herein.

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 9,1995 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 a7nyloliquefaciens, 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 amyloliquefacie7ls, 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 amyloliquefacie71s is characterized by the amino acid sequence: 1 10 20 AlaGlnSerValProTyrGlyValSerGln Ile LysAlaProAlaLeuHis SerGlnGly 30 40 TyrThrGlySerAsnValLysValAlaVal Ile AspSerGly Ile AspSer SerHisPro 50 60 <BR> <BR> <BR> <BR> <BR> <BR> <BR> AspLeuLysValAlaGlyGlyAlaSerMetValPro SerGluThrAsnProPheGlnAsp 70 80 <BR> <BR> <BR> <BR> <BR> <BR> <BR> AsnAsnSerHisGlyThrHisValAlaGlyTlirValAlaAlaLeuAsnAsnSerIle Gly 90 100 ValLeuGlyValAlaPro SerAla SerLeuTyrAlaValLysValLeuGlyAlaAspGly 110 120 SerGlyGlnTyr SerTrp Ile Ile AsnGly Ile GluTrpAla Ile AlaAsnAsnMetAsp 130 140 Val Ile AsnMetSerLeuGlyGlyPro SerGlySerAlaAlaLeuLysAlaAlaValAsp 150 160 <BR> <BR> <BR> <BR> <BR> <BR> <BR> LysAlaValAla SerGlyValValValValAlaAlaAlaGlyAsnGluGlyThrSerGly 170 180 Ser Ser SerThrValGlyTyrProGlyLysTyrPro SerVal Ile AlaValGlyAlaVal 190 200 <BR> <BR> <BR> <BR> <BR> <BR> <BR> AspSer SerAsnGlnArgAlaSerPheSer SerValGlyProGluLeuAspValMetAla 210 220 <BR> <BR> <BR> <BR> <BR> <BR> <BR> ProGlyValSer Ile GlnSerThrLeuProGlyAsnLysTyrGlyAlaTyrAsnGlyThr 230 240 <BR> <BR> <BR> <BR> <BR> <BR> <BR> SerMetAlaSerProHisValAlaGlyAlaAlaAlaLeu Ile LeuSerLysHisProAsn 250 260 <BR> <BR> <BR> <BR> <BR> <BR> <BR> TrpThrAsnThrGlnValArgSer SerLeuGluAsnThrThrThrLysLeuGlyAspSer 270 275 PheTyrTyrGlyLysLysGlyLeu Ile 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, Gln, Ala or Glu; the Gly at position Glyl69 is replaced with Ser; the Met at position Met222 is replaced with Gln, Phe, Cys, His, Asn, Glu, Ala or Thr; or b.) the Gly at position Glyl66 is replaced with Lys and the Met at position Met222 is replaced with Cys; or c.) the Gly at position Glyl60 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, Ser101, Gly102, Glu03, Ilex07, GlyllO, 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, Tyrol04, Alal52, Asnl55, Glu156, Glyl66, Glyl69, Phel89, Tyr217, and Met222 wherein both mutations cannot be made on the Asp32, Ser33, Tyrol04, Alal52, Asnl55, Glu156, Glyl66, Glyl69, Phel 89, 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, GlnlO3, TyslO4, SerlO5, IlelO7, AsnlO9, Asnl23, Leul26, Glyl27, Glyl28, Leul35, Glu156, Glyl66, Glu195, 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, Tyrol04, Asnl55, Glu156, Glyl66, Glyl69, Phel89, Tyr217, andMet222.

Preferred proteolytic enzymes, then, are selected from the group consisting of Alcalase (2), BPN', Protease A, Protease B, Protease D, and Protease F, and mixtures thereof. Protease F is most preferred.

Optional Is2¢redieB2ts The cosmetic compositions herein can comprise a wide variety of well known optional ingredients.

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 essential components 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, pastes and mousses. 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-¬4 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.

PolyAlydricalcohol Compositions for use herein comprise at least one polyhydric alcohol in a concentration of from about 0.1% to about 20%, preferably from about 0.5% to about 18%, more preferably from about 2% to about 15%, and even more preferably from about 5% to about 12% by weight, of the polyhydric alcohol, or mixtures thereof.

For the purposes of this invention a polyhydric alcohol is considered any organic compound comprising two, or more, alcohol functions or alkoxylated derivatives thereof.

In addition it is preferred that, if the composition has the form of an oil in water emulsion, that the polyhydric alcohol is present in the continuous phase.

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, propane-1,3 diol, propoxylated glycerine and mixtures thereof. The alkoxylated derivatives of any of the above polyhydric alcohols are also suitable for use herein.

Preferred polyhydric alcohols of the present invention are selected from glycerine, butylene glycol, propylene glycol, dipropylene glycol, polyethylene glycol, hexane triol, ethoxylated glycerine and propoxylated glycerine, and mixtures thereof. Most preferred polyhydric alcohols for use in the present invention are glycerine, butylene glycol, propylene glycol, polyethylene glycol and mixtures thereof.

Ski71 Care Active As a third essential ingredient the compositions herein comprise a skin care active at a level from about 0.1% to about 20%, preferably from about 1% to about 10%, more preferably from about 2% to about 8%, by weight.

The skin care active for use herein is selected from a vitamin B3 component, panthenol, vitamin E, vitamin E acetate, retinol, retinyl propionate, retinyl palmitate, retinoic acid, vitamin C, theobromine, a-hydroxyacid, farnesol, phytantriol, salicylic acid, and mixtures thereof.

The preferred skin care active for use herein from the viewpoint of providing improved skin hydration is a vitamin B3 component.

Vitamin B3 component The compositions of the present invention preferably comprise from about 0.01% to about 20%, more preferably from about 0.1% to about 15%, 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-CH20H (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 C1-C22, preferably C1- C16, more preferably C1-C6 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 preferred. 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. Preferred vitamin B3 compounds are niacinamide and tocopherol nicotinate. Niacinamide is more preferred.

Retinoids Another suitable skin care active is a retinoid. 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, retinoic acid and combinations thereof. More preferred are retinol, retinoic propionate, retinoic acid 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%).

It is very highly preferred that the compositions suitable for use in the present invention comprise a vitamin complex consisting of from about 1% to about 5%, by weight, of vitamin B3 compound or its derivatives; and from about 0.1% to about 1%, by weight, of a retinol compound or its derivatives in conjunction with from about 0.1% to about 1%, by weight, panthenol or its derivatives.

Additional 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% to about 15% and especially from about 0.5% to about 10%.

Preferred humectants include, but are not limited to, compounds selected from urea, D or DL panthenol, calcium pantothenate, royal jelly, panthetine, pantotheine, panthenyl ethyl ether, pangamic acid, pyridoxin, pantoyl lactose Vitamin B complex, hexane-1,2,6,- triol, guanidine or its derivatives. Highly preferred humectants are urea, panthenol and mixtures thereof. The above listed compounds may be incorporated singly or in combination.

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 W096/03964, 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.

Emollients The oil in water emulsions of the present invention generally comprise from about 1% to about 20%, preferably from about 1.5% to about 15%, more preferably from about 0.1% to about 8%, especially from about 0.5% to about 5% of a dermatologically acceptable emollient.

Emollients tend to lubricate the skin, increase the smoothness and suppleness of the skin, prevent or relieve dryness of the skin, and/or protect the skin. Emollients are typically water-immiscible, oily or waxy materials and emollients with high molecular weights can confer tacky properties to a topical composition. A wide variety of suitable emollients are known and may be used herein. Sagarin, Cosmetics. Science and Technology, 2nd Edition, Vol. 1, pp. 32-43 (1972), contains numerous examples of materials suitable as an emollient. All emollients discussed in application WO 00/24372 should be considered as suitable for use in the present invention although preferred examples are outlined in further detail below: i) Straight and branched chain hydrocarbons having from about 7 to about 40 carbon atoms, such as dodecane, squalane, cholesterol, hydrogenated polyisobutylene, isohexadecane, isoeicosane, isooctahexacontane, isohexapentacontahectane, and the C7-C40 isoparaffins, which are C7-C40 branched hydrocarbons. Suitable branched chain hydrocarbons for use herein are selected from 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. ii) C1-C30 alcohol esters of C1-C30 carboxylic acids, C12-15 alkyl benzoates, and of C2-C30 dicarboxylic acids, e. g. isononyl isononanoate, isostearyl neopentanoate. isodecyl octanoate, isodecyl isononanoate, tridecyl isononanoate, myristyl octanoate, octyl pelargonate, octyl isononanoate, myristyl myristate, myristyl neopentanoate, myristyl octanoate, isopropyl myristate, myristyl propionate, isopropyl stearate, isopropyl isostearate, methyl isostearate, behenyl behenate, dioctyl maleate, diisopropyl adipate, and diisopropyl dilinoleate and mixtures thereof. iii) C1-C30 mono-and poly-esters 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 INCI name sucrose polycottonseedate iv) Vegetable oils and hydrogenated vegetable oils. Examples of vegetable oils and hydrogenated vegetable oils include safflower oil, coconut oil, cottonseed oil, menhaden oil, palm kernel oil, palm oil, peanut oil, soybean oil, rapeseed oil, linseed oil, rice bran oil, pine oil, sesame oil, sunflower seed oil, partially and fully hydrogenated oils from the foregoing sources, and mixtures thereof v) Soluble or colloidally-soluble moisturising agents. Examples include 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.

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. Due to its poor skin feel properties castor oil is not a preferred emollient for use herein.

EnzulsifulsifierslSurfactants Compositions herein preferably contain an emulsifier and/or surfactant, generally to help disperse and suspend the disperse phase within the continuous aqueous phase. A surfactant may also be useful if the product is intended for skin cleansing. For convenience hereinafter emulsifiers will be referred to under the term'surfactants', thus 'surfactant (s)' will be used to refer to surface active agents whether used as emulsifiers or for other surfactant purposes such as skin cleansing. Known or conventional surfactants can be used in the composition, provided that the selected agent is chemically and physically compatible with essential components of the composition, and provides the desired characteristics. Suitable surfactants include non-silicone derived materials, and mixtures thereof. All surfactants discussed in application WO 00/24372 should be considered as suitable for use in the present invention.

The compositions of the present invention preferably comprise from about 0.05% to about 15% of a surfactant or mixture of surfactants. The exact surfactant or surfactant mixture chosen will depend upon the pH of the composition and the other components present.

Preferred surfactants are nonionic. Among the nonionic surfactants that are useful herein are those that can be broadly defined as condensation products of long chain alcohols, e. g.

C8-30 alcohols, with sugar or starch polymers ie glycosides. Other useful nonionic surfactants include the condensation products of alkylene oxides with fatty acids (i. e. alkylene oxide esters of fatty acids). These materials have the general formula RCO (X) nOH wherein R is a C10-30 alYl group, X is-OCH2CH2- (i. e. derived from ethylene glycol or oxide) or-OCH2CHCH3- (i. e. derived from propylene glycol or oxide), and n is an integer from about 6 to about 200. Other nonionic surfactants are the condensation products of alkylene oxides with 2 moles of fatty acids (i. e. alkylene oxide diesters of fatty acids). These materials have the general formula RCO (X) nOOCR wherein R is a C10-30 alkyl group, X is-OCH2CH2-(i. e. derived from ethylene glycol or oxide) or-OCH2CHCH3- (i. e. derived from propylene glycol or oxide), and n is an integer from about 6 to about 100. 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. Even further suitable examples include a mixture of cetearyl alcohols, cetearyl glucosides such as those available under the trade name Montanov 68 from Seppic and Emulgade PL68/50 available from Henkel..

The hydrophilic surfactants useful herein can alternatively or additionally include any of a wide variety of cationic, anionic, zwitterionic, and amphoteric surfactants such as are known in the art. See, e. g., McCutcheon's, Detergents and Emulsifiers, North American Edition (1986), published by Allured Publishing Corporation; U. S. Patent No. 5,011,681 to Ciotti et al., issued April 30,1991; U. S. Patent No. 4,421,769 to Dixon et al., issued December 20,1983; and U. S. Patent No. 3,755,560 to Dickert et al., issued August 28, 1973. A wide variety of anionic surfactants are also useful herein. See, e. g., U. S. Patent No. 3,929,678, to Laughlin et al., issued December 30,1975.

A wide variety of anionic surfactants are also useful herein. See, e. g., U. S. Patent No.

3,929,678, to Laughlin et al., issued December 30,1975. Exemplary anionic surfactants include the alkoyl isethionates (e. g., C12-C30), alkyl and alkyl ether sulfates and salts thereof, alkyl and alkyl ether phosphates and salts thereof, alkyl methyl taurates (e. g., C12 -C30), and soaps (e. g., alkali metal salts, e. g., sodium or potassium salts) of fatty acids.

Amphoteric and zwitterionic surfactants are also useful herein. Examples of amphoteric and zwitterionic surfactants which can be used in the compositions of the present invention are those which are broadly described as derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be straight or branched chain and wherein one of the aliphatic substituents contains from about 8 to about 22 carbon atoms (preferably Cg-Clg) and one contains an anionic water solubilising group, e. g., carboxy, sulfonate, sulfate, phosphate, or phosphonate. Examples are alkyl imino acetates, and iminodialkanoates and aminoalkanoates, imidazolinium and ammonium derivatives.

Other suitable amphoteric and zwitterionic surfactants are those selected from the group consisting of betaines, sultaines, hydroxysultaines, and branched and unbranched alkanoyl sarcosinates, and mixtures thereof.

Preferred emulsions of the present invention include a silicone containing emulsifier or surfactant. A wide variety of silicone emulsifiers are useful herein. These silicone emulsifiers are typically organically modified organopolysiloxanes, also known to those skilled in the art as silicone surfactants. Useful silicone emulsifiers include dimethicone copolyols. These materials are polydimethyl siloxanes which have been modified to include polyether side chains such as polyethylene oxide chains, polypropylene oxide chains, mixtures of these chains, and polyether chains containing moieties derived from both ethylene oxide and propylene oxide. Other examples include alkyl-modified dimethicone copolyols, i. e., compounds which contain C2-C30 pendant side chains. Still other useful dimethicone copolyols include materials having various cationic, anionic, amphoteric, and zwitterionic pendant moieties.

Polymeric Tizickeniiig Ageiits 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, crosslinked poly (N-vinylpyrrolidones), polysaccharides, natural or synthetic gums, polyvinylpyrrolidone, and polyvinylalcohol.

Suitable anionic thickening agents include acrylic acid/ethyl acrylate copolymers, carboxyvinyl polymers and crosslinked 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 W098/22085, or mixtures thereof.

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 mm2. s~l, preferably from about 0.65 to about 10,000 mm2. sol at 25°C. The viscosity can be measured by means of a glass capillary viscometer as set forth in Dow Coming 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 Coming as the Dow Coming 200 series. Also useful are essentially non-volatile polyalkylarylsiloxanes, for example, polymethylphenylsiloxanes, having viscosities of about 0.65 to 30,000 mm2. sol at 25°C. These siloxanes are available, for example, from the General Electric Company as SF 1075 methyl phenyl fluid or from Dow Coming 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. Included are non- volatile 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 min2s-1.

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 mm2. sol to about 100 mm2. s'1, 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 mm2. sol to about 100,000 mm2. s-i, preferably from 500 mun2. s-I to about 10,000 mm2. s'l.

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 mm2. s'l. An example of this silicone component is Dow Coming Q2-1403 (85% 5 mm2. s'l Dimethicone Fluid/15% Dimethiconol) and Dow Coming Q2-1401 available from Dow Corning.

Further silicone components suitable for use in a silicone oil phase herein are crosslinked polyorganosiloxane polymers, optionally dispersed in a fluid carrier. In general, when present the crosslinked 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 crosslinked by a crosslinking agent. Suitable crosslinking agents are disclosed in W098/22085. 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 crosslinked 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 crosslinked 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 W098/22085.

Suitable polydiorganosiloxane-polyalkylene copolymers are available commercially under the tradenames Belsil (RTM) from Wacker-Chemie GmbH, Geschäftsbereich 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 Coming DC3225C which has the CTFA designation Dimethicone/Dimethicone copolyol.

Suilscreeiis Compositions of the present invention preferably comprise an organic sunscreen.

Suitable sunscreens can have UVA absorbing properties, UVB absorbing properties or a mixture thereof. The exact amount of the sunscreen active will vary depending upon the desired Sun Protection Factor, ie the"SPF"of the composition as well as the desired level of UV protection. The compositions of the present invention preferably comprise an SPF of at least 10, preferably at least 15. SPF is a commonly used measure of photoprotection of a sunscreen against erythema. The SPF is defined as a ratio of the ultraviolet energy required to produce minimal erythema on protected skin to that required to products the same minimal erythema on unprotected skin in the same individual. See Federal Register, 43, No 166, pp. 38206-38269, August 25,1978). Amounts of the sunscreen used are typically from about 2% to about 20%, more typically from about 4% to about 14%.

Suitable sunscreens include, but are not limited to, those found in the CTFA International <BR> <BR> <BR> Cosmetic Ingredient Dictionafy and Handbook, 7ljt edition, volume 2 pp. 1672, edited by Wenninger and McEwen (The Cosmetic, Toiletry, and Fragrance Association, Inc., Washington, D. C., 1997).

The compositions of the present invention preferably comprise a UVA absorbing sunscreen actives which absorb UV radiation having a wavelength of from about 320nm to about 400nm. Suitable UVA absorbing sunscreen actives are selected from dibenzoylmethane derivatives, anthranilate derivatives such as methylanthranilate and homomethyl, 1-N-acetylanthranilate, and mixtures thereof. Examples of dibenzoylmethane sunscreen actives are described in US Patent No 4,387,089 issued to Depolo; and in Sunscreens: Development, Evaluation, and Regulatory Aspects edited by N. J. Lowe and N. A. Shaath, Marcel Dekker, Inc (1990). The UVA absorbing sunscreen active is preferably present in an amount to provide broad spectrum UVA protection either independently, or in combination with, other UV protective actives which may be present in the composition.

Preferred WA sunscreen actives are dibenzoylmethane sunscreen actives and their derivatives. They include, but are not limited to, those selected from 2- methyldibenzoylmethane, 4-methyldibenzoylmethane, 4-isopropyldibenzoylmethane, 4- tert-butyldibenzoylmethane, 2,4-dimethyldibenzoylmethane, 2,5- dimethyldibenzoylmethane, 4,4'-diisopropylbenzoylmethane, 4- (l, 1-dimethylethyl)-4'- methoxydibenzoylmethane, 2-methyl-5-isopropyl-4'-methoxydibenzoylmethane, 2- methyl-5-tert-butyl-4'-methoxy-dibenzoylmethane, 2,4-dimethyl-4'- methoxydibenzoylmethane, 2,6-dimethyl-4'-tert-butyl-4'methoxydibenzoylmethane, and mixtures thereof. Preferred dibenzoyl sunscreen actives include those selected from 4- (1, 1-dimethylethyl)-4'-methoxydibenzoylmethane, 4-isopropyldibenzoylmethane, and mixtures thereof. A more preferred sunscreen active is 4- (1, 1-dimethylethyl)-4'- methoxydibenzoylmethane.

The sunscreen active 4- (1, 1-dimethylethyl)-4'-methoxydibenzoylmethane, which is also known as butyl methoxydibenzoylmethane or Avobenzone, is commercially available under the names of Parsol@ 1789 from Givaudan Roure (International) S. A. (Basel, Switzerland) and Eusolex@ 9020 from Merck & Co., Inc (Whitehouse Station, NJ). The sunscreen 4-isoproplydibenzoylmethane, which is also known as isopropyldibenzoylmethane, is commercially available from Merck under the name of Eusolex0 8020.

The compositions of the present invention preferably further comprise a UVB sunscreen active which absorbs UV radiation having a wavelength of from about 290nin to abut 320nm. The compositions comprise an amount of the UVB sunscreen active which is safe and effective to provide UVB protection either independently, or in combination with, other UV protective actives which may be present in the compositions. The compositions preferably comprise from about 0.1% to abut 16%, more preferably from about 0.1% to about 12%, and most preferably from about 0.5% to about 8% by weight, of UVB absorbing organic sunscreen.

A wide variety of UVB sunscreen actives are suitable for use herein. Nonlimiting examples of such organic sunscreen actives are described in US Patent No 5,087,372 issued February 11,1992 to Haffey et al.; and US Patent Nos 5,073,371 and 5,073,372 both issued on December 17,1991 to Turner et al. and Segarin, et al., at Chapter VIII, pages 189 et seq., of Cosmetics Science and Technology. 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. Preferred UVB sunscreen actives are selected from 2-ethylhexyl-2-cyano-3, 2-ethylhexyl N, N-dimethyl-p- aminobenzoate, p-aminobenzoic acid, oxybenzone, homomenthyl salicylate, octyl salicylate, 4,4'-methoxy--butyldibenzoylmethane, 4-isopropyl dibenzoylmethane, 3- benzylidene camphor, 3- (4-methylbenzylidene) camphor, 3-diphenylacrylate (referred to as octocrylene), 2-phenyl-benzimidazole-5-sulphonic acid (PBSA), cinnamates and their derivatives such as 2-ethylhexyl-p-methoxycim1amate and octyl-p-methoxycinnamate, TEA salicylate, octyldimethyl PABA, camphor derivatives and their derivatives, and mixtures thereof. Preferred organic sunscreen actives are 2-ethylhexyl-2-cyano-3,3- diphenylacrylate (referred to as octocrylene), 2-phenyl-benzimidazole-5-sulphonic acid (PBSA), octyl-p-methoxycinnamate, and mixtures thereof. Salt and acid neutralised forms of the acidic sunscreens are also useful herein.

An agent may also be added to any of the compositions useful in the present invention to stabilise the UVA sunscreen to prevent it from photo-degrading on exposure to UV radiation and thereby maintaining its WA protection efficacy. A wide range of compounds have been cited as providing these stabilising properties and should be chosen to compliment both the UVA sunscreen and the composition as a whole. Suitable stabilising agents include, but are not limited to, those described in US Patents Nos 5,972,316; 5,968,485; 5,935,556; 5,827,508 and Patent WO 00/06110. Preferred examples of stabilising agents for use in the present invention include 2-ethylhexyl-2- cyano-3,3-diphenylacrylate (referred to as octocrylene), ethyl-2-cyano-3,3- diphenylacrylate, 2-ethylhexyl-3, 3-diphenylacrylate, ethyl-3,3-bis (4- methoxyphenyl) acrylate, and mixtures thereof. 2-ethylhexyl-2-cyano-3, 3- diphenylacrylate is most preferred.

An agent may also be added to any of the compositions useful in the present invention to improve the skin substantivity of those compositions, particularly to enhance their resistance to being washed off by water, or rubbed off. A preferred agent which will provide this benefit is a copolymer of ethylene and acrylic acid. Compositions comprising this copolymer are disclosed in U. S. Patent 4,663,157, Brock, issued May 5, 1987.

In addition to the organic sunscreens compositions of the present invention can additionally comprise inorganic physical sunblocks. Nonlimiting examples of suitable physical sunblocks are described in CTFA International Cosmetic Ingredient Dictionary, 6th Edition, 1995, pp. 1026-28 and 1103, Sayre, R. M. et al.,"Physical Sunscreens", J.

Soc. Cosmet. Chem., vol 41, no 2, pp. 103-109 (1990). Preferred inorganic physical sunblocks are zinc oxide and titanium dioxide, and mixtures thereof.

When used, the physical sunblocks are present in an amount such that the present compositions are transparent on the skin (ie non-whitening), preferably less than or equal to about 5%. When titanium dioxide is used, it can have an anatase, rutile, or amorphous structure. Physical sunblock particles, eg titanium dioxide and zinc oxide, can be uncoated or coated with a variety of materials including but not limited to amino acids, aluminium compounds such as alumina, aluminium stearate, aluminium laurate, and the like ; carboxylic acids and their salts eg stearic acid and its salts; phospholipids such as lecithin; organic silicone compounds ; inorganic silicone compounds such as silica and silicates; and mixtures thereof. A preferred titanium dioxide is commercially available from Tayca (Japan) and is distributed by Tri-K Industries (Emerson, NJ) under the MT micro-ionised series (eg MT 100SAS).

The compositions of the present invention preferably comprise from about 0.1% to about 10%, more preferably from about 0.1% to about 4%, and most preferably from about 0.5% to about 2.5%, by weight, of inorganic sunscreen.

A wide variety of optional ingredients such as neutralising agents, perfumes, and colouring agents, can also be added to the compositions herein. It is preferred that any additional ingredients enhance the skin softness/smoothness benefits of the product. In addition it is preferred that any such ingredients do not negatively impact the aesthetic properties of the product. As such high levels of proteins such as collagen and elastin are not preferred in compositions useful in the present invention.

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, and pantoyl lactose.

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 5ppm to about 500 ppm of the salt, based on the amount of metal ion.

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

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.

Other optional materials include keratolytic agents; 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-1, 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 building blocks thereof such as phytantriol and vitamin K and components thereof such as the fatty alcohol dodecatrienol; 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. Examples of alpha hydroxy acids include glycolic acid, lactic acid, malic acid, citric acid, glycolic acid in conjunction with ammonium glycolate, alpha-hydroxy ethanoic acid, alpha-hydroxyoctanoic acid, alpha-hydroxycaprylic acid, hydroxycaprylic acid, mixed fruit acid, tri-alpha hydroxy fruit acids, triple fruit acid, sugar cane extract, alpha hydroxy and botanical comprise, 1-alpha hydroxy acid and glycomer in crosslinked fatty acids alpha nutrium. Preferred examples of alpha hydroxy acids are glycolic acid and lactic acid. It is preferred that alpha hydroxy acids are used in levels of upto 10%.

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.

A safe and effective amount of an anti-inflammatory agent may be added to the compositions of the subject invention, preferably from about 0.1% to about 5%, more preferably from about 0.1% to about 2%, of the composition. The anti-inflammatory agent enhances the skin appearance benefits of the present invention, e. g., such agents contribute to a more uniform and acceptable skin tone or colour. The exact amount of anti-inflammatory agent to be used in the compositions will depend on the particular anti- inflammatory agent utilised since such agents vary widely in potency.

Compositions of the subject invention can further include an anti-oxidant/radical scavenger. The anti-oxidant/radical scavenger is especially useful for providing protection against UV radiation which can cause increased scaling or texture changes in the stratum corneum and against other environmental agents which can cause skin damage. Suitable amounts are from about 0.1% to about 10%, more preferably from about 1% to about 5%, of the composition. Anti-oxidants/radical scavengers such as ascorbic acid (vitamin C) and its salts.

The inclusion of a cheating agent is especially useful for providing protection against UV radiation which can contribute to excessive scaling or skin texture changes and against other environmental agents which can cause skin damage. A suitable amount is from about 0.01% to about 1%, more preferably from about 0.05% to about 0.5%, of the composition. Exemplary chelators that are useful herein are disclosed in U. S. Patent No.

5,487,884, incorporated herein by reference. Preferred chelators useful in compositions of the subject invention are ethylenediamine tetraacetic acid (EDTA), furildioxime, and derivatives thereof.

The compositions of the present invention can also comprise a skin lightening agent.

When used, the compositions preferably comprise from about 0.1% to about 10%, more preferably from about 0.2% to about 5%, also preferably from about 0.5% to about 2%, of a skin lightening agent. Suitable skin lightening agents include those known in the art, including kojic acid, arbutin, ascorbic acid and derivatives thereof, e. g., magnesium ascorbyl phosphate. Further skin lightening agents suitable for use herein also include those described in WO 95/34280 and WO 95/23780; each incorporated herein by reference.

Other optional materials include 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-1, 3-diol) and phenoxypropanol; anti- bacterials such as Irgasan (RTM) and phenoxyethanol (preferably at levels of from 0.1% to about 5%). Antibacterial agents such as TCC/TCS, also known as triclosan and trichlorocarbon are also useful in compositions of the present invention.

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 urn. Preferably the particulates useful herein have relatively narrow distributions, by which is meant that more than 50% of the particles fall within 3 pm 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 organosilicone and preferably organosilicone polymers. Preferred 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 llm and EA-209@ from Kobo which is an ethylene/acrylic acid copolymer having a median particle size of about 10 um, 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 preferred 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.

Suitably, the pH of the compositions herein is in the range from about 6.1 to about 10.0, preferably from about 7.0 to about 9.0, more preferably from about 8.0 to about 9.0 and even more preferably from about 8.0 to about 8.6. It is preferred that the pH of the final composition is adjusted by addition of acidic, basic or buffer salts as necessary.

The cosmetic compositions herein preferably have a water activity greater than 0.85, more preferably greater than 0.9, and most preferably greater than 0.95.

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).

Placebo Composition-Essential Features The cosmetic method described herein comprises a second phase during which a placebo composition is administered. As defined earlier the placebo composition can comprise any ingredients known to those skilled in the art providing that they are suitable for topical application. However the placebo composition should be essentially free of the biologically active enzyme. Highly preferred herein is that the placebo composition is formulated such that it maintains the benefit of the biologically active composition throughout phase two of the treatment cycle. In addition it is highly preferred herein that, during phase one of the treatment cycle, the placebo composition is administered simultaneously or sequentially with the cosmetic composition comprising the biological active. As such it is highly preferred that the placebo composition is formulated such that it is compatible with the cosmetic composition comprising the biologically active compound and the biologically active compound itself ie that it does not adversely affect the properties of this composition.

Any materials discussed above as suitable for use as an optional ingredient for the composition comprising the biologically active enzyme should be considered as suitable for use in the placebo composition for use in the present invention. It is highly preferred that the placebo compositions for use herein comprise from about 1% to about 50%, preferably from about 1.5% to about 15%, more preferably from about 0.1 % to about 8%, especially from about 0.5% to about 5%, by weight, of a dermatologically acceptable emollient. Furthermore it is preferred that the placebo compositions 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 10%, most preferably from about 1.5% to about 8%, by weight, of a skin care active. It is highly preferred that the skin care active is a vitamin complex comprises vitamin B3 compound or its derivatives; retinol compound or its derivatives; panthenol or its derivatives; and mixtures thereof.

Kit for Use in Cos) netic MetAlod The present invention further relates to a kit for use in a cosmetic method of the present invention wherein the kit is characterised in that it contains the following components: (a) from about 1 to about 365, preferably from about 1 to 50, more preferably from about 1 to 10, even more preferably from about 1 to 7 and most preferably from about 3 to 7 daily doses of a treatment composition comprising a biologically active enzyme, said biologically active enzyme being stably formulated; (b) from about 1 to about 365, preferably from about 1 to 100, more preferably from about 1 to 50, even more preferably from about 10 to 40 and most preferably from about 20 to 30 daily doses of a placebo composition; (c) usage instructions directing the user as to how to use the two compositions in the cosmetic method.

The kit can present the biologically active composition and the placebo composition in separate or a single dispensing unit. Similarly the dispensing units can dispense measured or unmeasured dosage units of the desired composition. Furthermore a daily dose of either composition from the kit can comprise a single dose or multiple doses which are administered at a single time point or throughout the day in compliance with the use instructions. The kit can be adapted to contain enough product for one or more treatment cycles.

It is preferred for use herein that the kit is adapted such that it comprises a single dispensing system comprising two or more chambers capable of delivering the daily dose of the biologically active composition during phase one of the cosmetic method cycle followed by a daily dose of the placebo composition during phase two of the treatment method cycle. A preferred enhancement of this adaptation is that the first chamber of the dispensing system comprises a composition wherein the biologically active compound is stably formulated and that the second chamber comprises a placebo composition such that when the compositions of the two chambers are mixed a biologically active composition is formed suitable for administration during phase one of the treatment regimen. This has the advantage of enabling the enzyme to be stabilised within a composition which is unsuitable for cosmetic application but wherein the final composition is suitable for application.

As such it is highly preferred that the first chamber of the dual chamber dispensing pack comprises: (a) from about from about 0.0001% to about 20%, preferably from about 0.01% to about 5%, more preferably from about 0.05% to about 2%, by weight, biologically active enzyme; (b) from about 20% to about 99%, preferably from about 50% to about 98%, more preferably from about 60 to about 95%, by weight, of a polyhydric alcohol; and (c) less than about 20% and preferably less than about 12%, by weight, of water.

Furthermore it is preferred that the first chamber also comprises from about 50 to about 400ppm of a metal salt selected from the group consisting of alkali metal salts, alkaline earth metal salts and mixtures thereof. It is preferred that the metal salts are selected from salts of sodium, calcium, magnesium and mixtures thereof.

In addition it is preferred that the second chamber of the pack comprises a placebo composition, preferably as an oil in water emulsion and the compositions from the two chambers are dispensed from the dispensing system simultaneously, preferably through a single nozzle.

Using a dual chamber dispensing kit such as that described above it is preferred that during phase one the treatment regimen the dispensing system simultaneously dispenses the biologically active composition and the placebo composition together, in a highly preferred embodiment that this occurs through a single nozzle, and that during phase two the dispensing system dispenses only the placebo composition. Furthermore the single dispensing system can be adapted to comprise enough material such that it is able to alternate between phase one and phase two of the treatment method for a period of one or more different treatment cycles. However it is highly preferred that the single dispensing system comprises enough material such that at the end of phase one no further cosmetic composition comprising biologically active material remains and that at the end of phase two no further placebo composition remains.

During phase one of the treatment cycle, ie when in a preferred embodiment the kit is simultaneously dispensing both the biologically active composition and placebo composition the operation of the dispensing system can be described as follows: where: A is the number of actuation required to dispense mass m of biologically active material m is the mass of biologically active material required (mg) R is the dispensing ratio of the dispensing system (based on volume) C is the concentration, mass per unit volume, of biologically active material in the dispensing system (ppm) V is the total volume dispensed per actuation of the pump (ml) p is the density of the biologically active composition (g/ml) Such a dual chamber single dispensing system operating as outlined above results in, during phase one of the treatment cycle that a dilution of the biologically active composition occurs. This needs to be taken into account when fonnulating the two compositions. In the highly preferred embodiment of this invention said dilution of the enzyme composition results in a dilution of the polyol, which on its turn results in a reactivation of the enzyme. Depending on the enzyme and the polyol used, enzyme reactivation can be expected to start at polyol concentrations of below 40%. The ratio in which the enzyme composition and the basic composition are delivered by the dispensing system depends for instance on the concentration of the polyol in the enzyme compositions, whereby the ratio should be adjusted in such a way to ensure reactivation of the enzyme. Furthermore, if topical use is desired, said ratio should be adjusted in such a way that the concentration level of the polyol, after mixing the enzyme with the basic composition, does not exceed the acceptable level for use in topical formulations. In addition the ratio should be set such that the consumer is unable to notice that the dispensing system is no longer dispensing the biologically active composition. This leads to a considerable reduction in the possibility of misuse and over exposure to the biologically active composition. It is preferred that, during phase one, the biologically active and placebo compositions are dispensed from the dispensing system in a weight ratio of from about 1: 1 to about 1: 50, preferably from about 1: 5 to about 1: 30, more preferably from about 1: 10 to about 1: 25, most preferably from about 1: 15 to about 1: 23.

Further examples of the pack are disclosed in patent WO 97/27841 which is incorporated herein by reference. Highly preferred is pack the Symbio pack, available from Airspray International.

Preparation of Coenpositions The compositions of the present invention are prepared by standard techniques well known to those skilled in the art. In general the aqueous phase and/or the oil phase would be prepared separately, with materials of similar phase partitioning being added in any order. If the final product is an emulsion, the two phases will then be combined with vigorous stirring. Any ingredients in the formulation with high volatility, or which are susceptible to hydrolysis at high temperatures, can be added with gentle stirring towards the end of the process, post emulsification if applicable.

Examples The following examples further illustrate the preferred embodiments within the scope of the present invention. These examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention as many variations of the invention are possible without departing from its spirit or scope. Unless otherwise indicated, all ingredients are expressed as a weight percentage of the active ingredient. Example Example Example Example Example Example 1 2 3 4 5 6 Phase 1 composition % w/w % w/w % w/w % w/w °/a w/w % w/w DEIONISED qs qs qs qs qs qs WATER GLYCERIN 12.00 12.00 10.00 12.00 12.00 12.00 ISOHEXADECA 2.95 3.08 3.12 3.14 3.14 3.14 NE POLYACRYLA 1.62 1.69 1.71 1.73 1.73 1.73 MIDE & C13-14 ISOPARAFFIN & LAURETH-71 DIMETHICONE 1.97 2.05 2.08 2.10 2.10 2.10 & DIMETHICONO L2 ISOPROPYL 1.31 1.37 1.38 1.39 1.39 1.39 ISOSTEARATE SORBITAN 0.98 1.03 1.04 1. 05 1.05 1.05 STEARATE & SUCROSE COCOATE3 CETYL 0.71 0.74 0.75 0.75 0.75 0.75 ALCOHOL SEFA 0.66 0.69 0.70 0.70 0.70 0.70 COTTONATE STEARYL 0. 47 0.49 0.50 0.50 0.50 0.50 ALCOHOL BENZYL 0.25 0.26 0.26 0.26 0.26 0.26 ALCOHOL ETHYLPARABE 0.20 0.21 0.21 0.21 0.21 0.21 N PROPYLPARAB 0. 10 0.10 0.10 0.10 0.10 0.10 EN DISODIUM 0.10 0.10 0.10 0. 10 0. 10 0. 10 EDTA POLYOXYETHY 0.10 0.10 0.10 0.10 0.10 0.10 LENE-100 STEARATE3 STEARIC ACID 0.10 0.10 0.10 0.10 0.10 0.10 SODIUM 0.05 0.05 0.05 0.05 0.05 0.05 HYDROXIDE Protease enzyme 100 1000 50 500 100.00 1000.00 pom) 4 Overall Active 0.4mg 4.0mg 0.2mg 2.0mg 0.4mg 4mg delivered per single application Phase 2 composition DEIONISED qs qs qs qs qs qs WATER GLYCERIN 3.67 6.76 6.15 8.77 6.93 10.00 ISOHEXADECA 3.22 3.23 3.24 3.24 3.00 3.00 NE Niacinamide 2.00 0.00 2.00 3.50 2.00 3.50 Panthenol 0.50 0.00 0.50 0.00 0.50 0.50 Vitamin E Acetate 0.50 0.00 0.50 0.00 0.50 0.50 DIMETHICONE 2.15 2.15 2.16 2.17 2.00 2.00 & DIMETHICONO L2 ISOPROPYL 1.43 1.44 1.44 1.44 1.33 1.33 ISOSTEARATE SORBITAN 1.07 1.08 1.08 1.09 1. 00 1. 00 STEARATE & SUCROSE COCOTTE3 CETYL 0.77 0.78 0.78 0.78 0.72 0.72 ALCOHOL SEFA 0.72 0.72 0.73 0.72.0.67 0.67 COTTONATE STEARYL 0.51 0.51 0.52 0.52 0.48 0.48 ALCOHOL BENZYL 0.27 0.27 0.27 0.27 0.25 0.25 ALCOHOL ETHYLPARABE 0.22 0.22 0.22 0.22 0.20 0.20 N PROPYLPARAB 0.11 0.11 0.10 0.10 0.10 0.10 EN DISODIUM 0. 11 0.11 0.10 0. 10 0.10 0. 10 EDTA POLYOXYETHY 0. 11 0. 11 0. 10 0. 10 0. 10 0. 10 LENE-100 STEARATE3 STEARIC ACID 0.11 0.11 0.10 0.10 0. 10 0.10 SODIUM 0. 05 0. 05 0. 05 0. 05 0. 01 0. 01 HYDROXIDE Protease enzyme 0 0 0 0 0 0 (ppm) Delivery system Single5 Single5 Single5 Single5 Two Two Pack Pack Pack Pack Packs Packs Treatment Cycle Phase 1 5 days 3 days 10 days 8 days 5 days 3 days Phase 2 23 days 11 days 46 ays 20 days 23 days 20 days Preferred 12 per 24 per 6 per 12 per 12 per 12 per number of cycles/year year year year year year treatment 1. Supplied by Seppic, 75 Quai D'Orsay, Paris 2. Supplied by Dow Corning, Kings Court, 185 Kinds Rd, Reading, Berks, RG1 4EX 3. Supplied ICI, PO Box 90, Wilton Centre, Middlesborough, Cleveland, England. TS6 8JE 4. Genencor International, Palo Alto, California, US 5. Symbio Pack supplied by Airspray International, Allumer, Netherlands Compositions were prepared according to the instructions below.

Manufacture of Lotion/Skin Cream Heat a mixture of water, glycerine, Sorbitan stearate/sucrose cocoate (if applicable) gentle stirring.

Simultaneously, mix and heat the following materials: Vitamin E Acetate, Isohexadecane, Isopropyl Isostearate, Cetyl Alcohol, Petrolatum, Ispropyl Palmitate, Behenyl Alcohol, Stearyl Alcohol, Ethyl Paraben, Propyl paraben, PEG 100 stearate, stearic acid and Cetearyl Glucoside/Cetearyl Alcohol (if applicable) When the two mixtures are at 75-80C, add the mixtures together and mix at high shear to create an emulison.

Cool the mixture and add Niacinamide, panthenol, sodium hydroxide Polyacrylamide & C13-14 Isoparaffin & Laureth 7 during the cooling cycle.

At the point of finishing the batch add Dimethicone and Dimethiconol and mix briefly with high shear. Allow the mixture to cool to room temperature Enzyme solution Mix the enzyme with a suitable solvent to dissolve the material, in the required amounts to achieve the final dilution.

Product is then packed into the final kit.

The compositions when used in compliance with the treatment regimen, display excellent skin hydration, skin softness and skin smoothness benefits.