WO1995005159A1 - Acylated hydroxyalkanoates and their uses - Google Patents

Abstract

A composition for topical application includes a hydroxyalkanoate derivative having structure (I), where R1 represents H- or acyl, R2 represents alkyl of at least 2 carbon atoms, R3 represents H-, alkyl, substituted or interrupted alkyl or a metallic, ammonium or alkanolammonium counterion. The hydroxyalkanoate derivative penetrates deeply into the skin and undergoes cleavage by enzymes in the skin to liberate the corresponding hydroxyalkanoate which benefits skin condition.

Description

ACYLATED HYDROXYALKANOATES AND THEIR USES

FIELD OF INVENTION The invention relates to the topical use of hydroxy alkanoate derivatives for improving the condition of human skin, particularly for moisturising the skin, hair, nails and other epithelial tissues, including the mucosae, also for reducing skin drying and for delaying the appearance of or eliminating wrinkles and fine lines on the skin.

The invention also relates to a method for the delivery to the epidermis of a hydroxyalkanoate for moisturising the skin, hair and nail and to compositions for topical use to achieve this benefit.

BACKGROUND TO THE INVENTION

Human skin consists essentially of two layers: the inner dermis and the outer epidermis, the former functioning mainly as a mechanical support for the latter.

The epidermis, which can be as little as 0.06 mm thick in the case of the eye lid to as much as 0.8 mm on the foot, itself comprises four or five layers, namely:

(i) the Stratum Malpigii, which is the germinative layer of cells at the base of the epidermis that adjoins the Dermis.

(ii) the Stratum Spinosum, the prickle cell layer which represents the first morphologically distinct stage in the differentiation of epidermal cells. It consists of numerous evenly spaced intercellular bridges - tonofilaments - each with a central thickening. The margins of several of these thickenings accounts for the appearance of desmosomes . The tonofilaments form the earliest precursor of keratin. (iii) the Stratum Granulosum, the granular layer immediately above the prickle cell layer, which contains basophilic granules of keratohyalin. Also present in the Stratum Granulosum are the bridges (desmosomes and tono filaments seen in the prickle cell layers) , but their close apposition renders them less visible.

(iv) the Stratum Lucidum, seen especially in the epidermis of the hand and foot, comprises cells which are of even thickness and essentially non-nuclear.

(v) the Stratum Corneum, which lies above the Stratum Lucidum (when present) , forms the outermost layer of the epidermis. The Stratum Corneum is composed of dead, flat, fully keratinized cells which lie on top of one another to a depth of from 0.02 to 0.8 mm. The Stratum corneum also possesses lipid materials which effectively form a waterproof barrier to the external surface of the skin.

Beneath the epidermis is the dermis which is composed of collagen, usually accompanied by elastin and reticulin. These materials are fibrous proteins embedded in a mucopolysaccharide ground substance. Several cellular types, together with nervous and vascular networks, are found in the dermis, together with specialised appendages, including sweat glands, hair follicles with associated sebaceous glands.

A soft, supple and flexible skin has a marked cosmetic appeal and these characteristics are attributes of normal functioning epidermis, particularly with respect to the young human subject. The outer layer of the epidermis, i.e. the stratum corneum, can however become dry and flaky following exposure to adverse climatic conditions, or by excessive contact with detergents or solvents which results in a loss of skin moisture. Consequently, the skin can lose its soft, supple and flexible characteristics.

Emollients such as fats, phospholipids and stearols, have in the past been used to soften dry skin, but this can leave the skin greasy and unattractive. As an alternative, the topical application to the skin of classical humectants does not alleviate this problem, as these compounds are not particularly skin substantive and are generally rinsed from the skin during washing.

It is therefore apparent that there exists a continuing need for an effective methods for treating dry flaky skin to restore its original soft, supple and flexible characteristics, and indeed for maintaining these attributes of normal functioning epidermis.

In an article by Baiocchi et al in Cosmetics and Perfumery 90, 31-34 (1975) , it is stated that sodium stearoyl lactylate, when incorporated in a hand cream or lotion, results in a subjectively smooth and supple but not excessively greasy feeling when such creams or lotions are topically applied to the hands. However, the primary reason for including this lactylate in such formulations is to function as a very efficient emulsifier.

In an article by Osipow et al in Drug & Cosmet Ind, May 1969, 64ff, it is disclosed that sodium stearoyl lactylate may be used in oil-in-water cosmetic creams as the emulsifier to impart body, lubricity and opalescence to the cream. It is alleged that its absorption to the skin may enhance its softening action.

In another article by Murphy in Cosmetics and Toiletries 94 , 43ff (1979) , the sorption of acyl lactylates on the skin was examined by using pigskin as a model. It is described that sodium isostearoyl lactylate appears to reduce dryness and scaling of skin and restores a healthy texture to dry skin.

Murphy in Cosmetics and Toiletries 92_., 31 (1978) discusses a systematic approach to skin moisturisation and concludes that a combination of the pyrrolidone carboxylic acid

(PCA) sodium.salt, sodium lactate and lactic acid can be used as effective humectants to hold moisture in the skin.

EP 0 530 866 (Unilever) concerns novel sulfoxy alkanoate surfactants which it is believed are broken down by enzymes naturally present in the skin, or are naturally hydrolysed upon contact with the skin to yield "Benefit Reagents" e.g. Hydroxy acid and/or Fatty Alcohol.

EP 0 442 708 (Unilever) discloses cosmetic compositions containing 2-hydroxy alkanoic acids. Due to the presence of these acids in compositions, several benefits are imparted to the skin, such .as an increase in the elasticity of the skin, particularly of the stratum corneum. Similarly, EP 0 007 785 (Unilever) discloses cosmetic compositions comprising 2-hydroxy alkanoic acids, which also give various skin benefits when topically applied to the skin.

However, the extent to which the moisturisation of skin, or its ability to remain moist without becoming dry, by topical application of so-called "moisturisers" as proposed by other workers in the field of cosmetic science, is not great. A search has therefore been conducted for other active materials that can be employed in this way for enhancing the moisturisation of skin or, once moisturised, for restricting the extent to which skin moisture loss will occur.

It has long been recognised that cream or lotion formulations containing lactic acid, usually as lactate ions in products near neutral pH, when applied topically to the skin, can improve the flexibility and texture of the skin, and it is believed that lactate contributed to this effect. In studying this approach, we have applied such creams and lotions to the skin and have shown that although lactate can thereby be deposited on the surface of the stratum corneum which forms the outermost part of the skin, very little actually penetrates through the stratum corneum to the underlying regions of the epidermis, namely to the Stratum Granulosum and other strata below. This is thought to be due to the hydrophilic (i.e. lipophobic) property of lactate ions which renders them relatively incompatible with the lipids naturally present in the Stratum Corneum, and which thereby present a barrier to the adsorption of hydrophillic molecules.

While investigating the properties of derivatives of lactic acid that were more lipophilic than lactate itself, (eg. sodium lactate) we discovered that a range of acyl lactylates were more readily adsorbed on contact with the skin and indeed migrated through the skin to reach the epidermis beneath the Stratum Corneum at a rate and to an extent that was far superior to lactate ions. We also made the discovery using labelled materials and radio tracer techniques, that these acyl lactylate molecules were cleaved within the epidermis, most likely by the presence of endogenous esterases or other enzymes, to form lactate ions deep in the epidermis, as far as the Stratum Malpigii.

We extended our study of acyl lactylates to other molecules in the homologous series, where the head group is not lactylate but an alkyl hydroxy alkanoate of longer chain length, and we were again able to show that molecular cleavage occurred in the epidermis, following topical application of these molecules, to release in situ the corresponding hydroxy acid. This longer chain length hydroxy acid was also shown to possess properties which enhanced the moisturisation of skin and/or reduced the extent to which moisture is lost from the skin.

The invention is accordingly concerned with the generation in situ in the epidermis of hydroxy alkanoic acids and the topical use of their corresponding acyl or alkyl derivatives to achieve this end.

DEFINITION OF THE INVENTION

Accordingly, one aspect of the invention provides the use of an effective amount of at least 0.001% by weight based on the total composition of a hydroxy alkanoate derivative having the structure (1) :

?P^Hq 0

R¹ [O-CH C]_m OR₃ (1) 0 where R^x represents H- or C_j. .O_j.^-C-

R³ represents H- , C_xH_yO_zN_w- or a metallic, ammonium or alkanolammonium, counterion, p is an integer from 2 to 22, q is an integer from 5 to 45, x is an integer of from 1 to 20, y is an integer of from 3 to 41, z is O, or an integer of from 1 to 10, w is O, or an integer of from 1 to 5, and m is an integer of from 1 to 5 provided that when R¹ is H- , then R³ is C_xH_yO_zN_w- , or when

O R~ is H- or a countenon, then R is C_XH 0₂N_wC-

to deliver to the epidermis, as a moisturiser for the skin, the corresponding 2-hydroxyalkanoate having the structure (2) : C_pH_g 0

I II

HO-CH C - OX (2)

where X represents -H or a counterion;

in a composition intended for topical application to human skin; said compositions otherwise comprising a cosmetically acceptable vehicle.

The invention also provides a method for delivering to the epidermis a 2-hydroxy alkanoate having the structure (2) :

which comprises the steps of

i) applying topically to the skin a composition comprising the corresponding hydroxy alkanoaate derivative having the structure (1) :

?F^Hq o

R¹ [O-CH- ^■C]_ra OR, (1)

as hereinbefore defined,

ii) leaving the composition in contact with the skin for at least 10 seconds to permit the hydroxy alkanoate derivative to penetrate through the stratum corneum to reach the lower strata of the epidermis, and

iii) cleaving the hydroxy alkanoate derivative in the epidermis by contact with esterases to provide the 2- hydroxy alkanoate.

The invention also provides a composition suitable for topical application to the skin, hair, nails, mucosae and other epithelial tissue, which composition comprises:

i) a hydroxy alkanoate derivative having the above defined structure (1) :

R .¹ [O- ΪC^ΛH ! C] _m ^' OR₃ ( 1 )

ii) a cosmetically acceptable vehicle for the hydroxy alkanoate derivative;

the hydroxyalkanoate derivative possessing the ability of penetrating the stratum corneum and hydrolysing by enzymic cleavage within the epidermis to yield the corresponding hydroxyalkanoate having the structure (2) :

?P^Hq O

HO- CH C - OX ( 2 ) thereby to moisturise the epithelial tissue.

In the above formulae, it is strongly preferred that R¹ is an acyl group of the above mentioned general formulae O O

C_xH_yO_zN_wC- especially an acyl group of the formula C_xH_yC-

In such a group the value of x is preferably at least 5 A value of at least 9, for instance 9 to 13, is more preferred.

It is preferred that C_pH_q- represents an alkyl group, especially a straight chain alkyl group. In an alkyl group of formula C_pH_q- the value of q must of course be 2p+l. Less preferred us that C_pH is alkenyl, such as straight chain alkenyl .

It is preferred that the vehicle includes water. Certain preferred compositions include water-immiscible oil and/or water-soluble organic solvent such as ethanol. The amount of oil does not usually exceed 50% by weight of the composition, neither does the amount of water-soluble solvent, although in total these non-water materials may provide more than 50% by weight of the composition.

The invention may be applied in the context of a composition which is applied to skin, especially the face, and either left there or at least not removed immediately.

Penetration into the skin of hydroxyalkanoate derivative from such compositions can occur even when the hydroxyalkanoate is present at rather low concentration.

Such compositions frequently include some oil or oily material or organic solvent which is water soluble.

An alternative is to apply the invention in the context of a washing composition containing surfactant, and intended to be rinsed off after use. With such a composition it will probably be desired to include the hydroxyalkanoate derivative at a higher concentration.

In addition to their benefits in moisturising skin, topical application of the hydroxyalkanoate derivatives can also improve the skin surface in other respects by eliminating or by preventing the development of, or at least slowing, skin surfaces changes. Examples of such changes include, fine lines, wrinkles, blemishes, blotches, nodules, atrophy, pigmented spots, lesions, elastoic changes characterised by leathery, coarse, rough, dry and yellowish skin, photo-damages skin, loss of elasticity and other changes associated with ageing. In summary, the hydroxyalkanoate derivatives can also have marked antiaging benefits to the skin.

The topical application of the hydroxyalkanoate derivatives can also be used for the treatment of spots, pimples and acne, especially for the inhibition of Propionibacterium acnes, which is believed to be a causative organism in the development of acne comedones.

Topical application of the hydroxyalkanoate derivatives can also be used in the treatment of dandruff on the scalp, again in view of the ability of these derivatives to inhibit microorganisms implicated in the development of dandruff.

DETAILED DISCLOSURE OF THE INVENTION

The hydroxy alkanoate derivatives

Hydroxy alkanoate derivatives for use in accordance with the invention are chosen from those having the structure (1) as herein defined, and are generally acyl or alkyl derivatives. Acyl derivatives are particularly preferred.

Examples of such acyl derivatives of hydroxy alkanoates include:

i) those where R¹ in structure (1) represents the acyl group: O

C_χH_y ICI- and where C_pH_ represents an alkyl group in the series CH₃CH₂- to CH₃(CH₂)₁₉- m is 1 to 5, and

R³ represents -H, or an alkali metal, an alkaline earth metal, ammonium or an alkanolammonium counterion. Specific examples are the sodium, potassium, calcium, ammonium or triethanolammonium salts or free acids of :

the n-propionyl derivative of 2-hydroxyoctanoate, i.e. 2- (n-propionyloxy) octanoate, and the analogous n-butanoyl, n-hexanoyl, n-octanoyl, n-decanoyl, n-dodecanoy1, n-tetradecanoyl, n-hexadecanoyl, n-octadecanoyl, n-linoleoyl, n-linolenoyl, γ-linolenoyl, n-arachidonoyl, and columbinoyl derivatives^'of 2-hydroxyoctanoate,

2- (n-octanoyloxy)butanoate 2-(n-decanoy1oxy)hexanoate

2- (n-dodecanoyloxy)butanoate

2- (n-dodecanoyloxy) hexanoaate

2- (n-dodecanoyloxy)decanoate

2- (n-dodecanoyloxy) dodecanoate 2- (n-dodecanoyloxy) tetradecanoate

2- (n-dodecanoyloxy) hexadecanoate and

2- (n-dodecanoyloxyoctadecanoate, and the corresponding acyl derivatives of di-, tri-, tetra and pentahydroxy alkanoates.

ii) those where R¹ in Structure (1) represents the acyl group:

O C_χH_y ICI-

and where C_pH_g represents an alkyl group in the series CH₃CH₂- to CH₃ (CH₂ ) ₁₉- ^Cx^Hy represents a branched chain alkyl group m is 1 to 5, and

R represents -H, an alkali metal, an alkaline earth metal, ammonium or an alkanolammonium counterion.

Specific examples are the sodium, potassium, calcium, ammonium or triethanolammonium salts or free acids of:

(iso-butanoyloxy)butanoate

(iso-hexanoyloxy)butanoate

(iso-octanoyloxy)butanoate

(iso-octadecanoyloxy)butanoate

(iso-butanoyloxy)octanoate

(iso-octanoyloxy)octanoate

(iso-octadecanoyloxy) octanoaate

(iso-dodecanoyloxy) octanoate

(ethylglycoloyloxy)butanoate

(ethylglycoloyloxy) octanoate

(leucoyloxy)butanoate

(leucoyloxy) octanoate

(mandeloyloxy)butanoate

(mandeloyloxy) octanoate

(ethyl glycoloyloxy) octanoate

(12-hydroxy octadecanoyloxy) octanoate

(ethyl glycoloyloxy)butanoate

(12-hydroxy octadecanoyloxy)butanoate, and the corresponding acyl derivatives of di-, tri- tetra and pentahydroxyalkanoates.

iii) those where R¹ in structure (1) represents the acyl group:

O

II C_χH_yO_zN_wC-

where C_pH represents an alkyl group in the series CH₃CH₂ - to CH₃ ( CH₂ ) ₁₉ - m is 1 to 5

R³ represents -H, or an alkali metal, an alkaline earth metal, ammonium or alkanolammonium counterion.

Specific examples are the sodium, potassium, calcium, ammonium or triethanolammonium salts or free acids of

2- (cocoamidopropanoyloxy)butanoate

2- (pyroglutamoyloxy)butanoate 2- (cholesteroyloxy)butanoate

2- (ceramidinoyloxy)butanoate

2- (cocoamidopropanoyloxy) octanoate

2- (pyroglutamoyloxy) octanoate

2- (cholesteroyloxy) octanoate 2- (ceramidinoylox) octanoate, and the corresponding acyl derivatives of di-, tri-, tetra- and pentahydroxy alkanoates.

Some compounds of this invention in which R¹ is an acyl group are known compounds for which preparative routes have been published. References includes US-A-4058540, preparations given in EP-A-54435 and Taylor et al, Tetrahedron letters £0_. 5285 (19) .

A route for the preparation of such compounds comprises: i) forming an acyl chloride by reacting an alkanoic acid with oxalyl chloride, thus:

COC1 COOH 2 C_χH O_zN_wCOOH + | > 2 C_χH O_zN_wCOCl + |

COC1 COOH

ii) acylating a 2-hydroxy alkanoic acid with the acyl chloride to form the acyl 2-hydroxy alkanoate thus:

OH C H

C_χHyO^COCl + CpH IgCHCOOH > C_xH_y0_zN_wC00CHIC00H + HCl Examples of alkyl esters of hydroxy alkanoates, within structure (1) are:

those where R¹ in structure (1) represents -H, R³ represents C_XH - , and m is 1.

Specific examples are:

methyl 2-hydroxybutanoate n-butyl 2-hydroxybutanoate n-hexyl 2-hydroxybutanoate n-octyl 2-hydroxybutanoate n-dodecyl 2-hydroxybutanoate n-octadecyl 2-hydroxybutanoate ethyl 2-hydroxyhexanoate ethyl 2-hydroxyoctanoate, and n-dodecyl 2-hydroxyoctanoate.

The 2-hydroxyalkanoic acids are well known compounds. Their alkyl esters can be made by conventional esterification techniques.

It is not intended that the above examples form an exhaustive list of acyl derivatives and alkyl esters of hydroxy alkanoates, as there are many more compounds that comply with the structure (1) , that can be used in accordance with the invention.

The amount of hydroxyalkanoate derivative to be employed in accordance with the invention as an effective amount will normally be from 0.001 to 50%, preferably at least 0.1%, e.g. from 0.1 to 30%, and most preferably at least 0.5%, e.g. from 0.5 to 20% by weight of the composition.

As will be explained and illustrated later in the specification, the composition for use in accordance with the invention can either be employed as a "leave-on" product, in which case it is intended to be applied to the skin and left in place, or it can be employed as a "rinse- off" or "wipe-off" product, usually for cleansing the skin, in which case it will normally be rinsed or wiped from the skin shortly after application, e.g., after washing. Thus for "leave-on" products, the most preferred amount of hydroxyalkanoate derivative will be from 0.1 to 2%, whereas, for "rinse-off" or "wipe-off" products, the corresponding preferred amount will be from 0.1 to 20% or more, in both instances expressed in terms of percentage by weight of the composition.

Cleansing Compositions A significant form of this invention is therefore a cleansing composition containing from 5 to 40% by weight of an acyl derivative of a hydroxyalkanoate, having the above structure (1) in which R³ represents -H or a metallic, ammonium or alkanolammonium counterion, while R¹

O 0 represents C_y iyO^^-C- , preferably C_XH C- . Such a cleansing composition generally also contains water.

In a related aspect, the invention provides a method for cleaning the skin or the hair which comprises the steps of (i) applying to the skin or hair cleansing composition as specified above;

(ii) forming a lather on the skin or hair by massaging in the presence of added water, thereby to cleanse the skin or hair; and (iii) subsequently rinsing the lather from the skin or hair with water.

Cosmeticallv Acceptable Vehicles

The hydroxyalkanoate derivatives, as herein described, will in use normally be applied to human skin in the form of a composition that also comprises a cosmetically acceptable vehicle, that is intended to facilitate the distribution of the hydroxyalkanoate derivative on and over the skin surface at an appropriate concentration.

The composition can thus be solid, semi-solid or liquid in nature, dependent upon the choice of vehicle. The vehicle itself can be inert or it can possess beneficial physiological properties of its own.

The selection of a vehicle for this purpose presents a wide range of possibilities depending on the required product form of the composition. Suitable vehicles can be classified as described hereinafter.

Vehicles are therefore substances that can act as diluents, dispersants, or solvents for the hydroxy alkanoate derivative which ensures that it can be applied to and distributed evenly over the skin at an appropriate concentration. The vehicle is preferably one which can aid penetration of the hydroxy alkanoate derivative deep into the epidermis, to enable it more readily to influence the condition of the skin.

Compositions according to the invention can include water as a vehicle, and/or at least one cosmetically acceptable vehicle other than water.

Vehicles other than water can include liquid or solid emollients, solvents, humectants, thickeners and powders. Examples of each of these types of vehicle, which can be used singly or as mixtures of one or more vehicles, are as follows:

Emollients, such as stearyl alcohol, glyceryl monoricinoleate, mink oil, cetyl alcohol, isopropyl isostearate, stearic acid, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isocetyl alcohol, eicosanyl alcohol, behenyl alcohol, cetyl palmitate, silicone oils such as dimethylpolysiloxane, di-n-butyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, cocoa butter, corn oil, cotton seed oil, olive oil, palm kernel oil, rapeseed oil, safflower seed oil, evening primrose oil, soybean oil, sunflower seed oil, avocado oil, sesame seed oil, coconut oil, arachis oil, castor oil, acetylated lanolin alcohols, petroleum jelly, mineral oil, squalane, squalene, butyl myristate, isostearic acid, palmitic acid, isopropyl linoleate, decyl oleate, myristyl myristate;

Propellants for aerosols, such as propane, butane, isobutane, dimethyl ether, carbon dioxide, nitrous oxide;

Solvents, such as ethyl alcohol, methylene chloride, isopropanol, acetone, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, dimethyl sulphoxide, dimethyl formamide, tetrahydrofuran;

Powders, such as chalk, talc, fullers earth, kaolin, starch, gums, colloidal silica sodium polyacrylate, tetra alkyl and/or trialkyl aryl ammonium smectites, chemically modified magnesium aluminium silicate, organically modified montmorillonite clay, hydrated aluminium silicate, fumed silica, carboxyvinyl polymer, sodium carboxymethyl cellulose, ethylene glycol monostearate, ethylene glycol distearate;

The cosmetically acceptable vehicle will usually form from 10 to 99.99%, preferably from 10 to 99% and most preferably from 50 to 99% by weight of the composition, and can, in the absence of other cosmetic adjuncts, form the balance of the composition.

OPTIONAL SKIN BENEFIT MATERIALS AND COSMETIC ADJUNCTS

Penetration Enhancer

The composition for use according to the invention can also optionally comprise a penetration enhancer which can potentiate the benefit of the hydroxy alkanoate derivative by improving its delivery through the stratum corneum to its site of action deep in the epidermis.

The penetration enhancer can accordingly function in a variety of ways. It can for example, improve the distribution of the hydroxy alkanoate derivative on the skin surface, or it can increase its partition into the stratum corneum and beyond from the composition when applied topically, so aiding its passage to a lower level within the epidermis. Other mechanisms enhancing the benefit of the hydroxy alkanoate derivative may also be involved.

Examples of penetration enhancers include

2-methyl propan-2-ol

Propan-2-ol Hexan-2, 5-diol

POE(2) ethyl ether

Di (2-hydroxypropyl) ether

Pentan-2,4-diol

POE(2) methyl ether Propan-1-ol

1, 4 Dioxane

Butan-l,4-diol

Propylene glycol dipelargonate

Polyoxypropylene 15 stearyl ether Octyl alcohol

POE ester of oleyl alcohol

Oleyl alcohol Lauryl alcohol

Dioctyl adipate

Dicapryl adipate

Diisopropyl adipate Diisopropyl sebacate

Dibutyl sebacate

Diethyl sebacate

Dimethyl sebacate

Dioctyl sebacate Dibutyl suberate

Dioctyl azelate

Dibenzyl sebacate

Dibutyl phthalate

Dibutyl azelate Ethyl myristate

Dimethyl azelate

Butyl myristate

Dibutyl succinate

Didecyl phthalate Decyl oleate

Ethyl caproate

Ethyl salicylate

Isopropyl myristate

Isopropyl palmitate Ethyl laurate

2-ethyl-hexyl pelargonate

Isopropyl isostearate

Butyl laurate

Benzyl benzoate Butyl benzoate

Hexyl laurate

Ethyl caprate

Ethyl caprylate

Butyl stearate Benzyl salicylate

2-Pyrrolidone

1-Methyl-2-pyrrolidone 5-Methyl-2-pyrrolidone 1, 5-Dimethyl-2-pyrrolidone 1-Ethyl-2-pyrrolidone Sugar esters Tetrahydrofurfural alcohol Urea

Diethyl-m-toluamide, and l-Dodecylazacyloheptan-2-one

The amount of penetration enhancer, when employed in accordance with the invention, will normally be from 0.1 to 50%, preferably from 0.5 to 25% and most preferably from 0.5 to 10% by weight of the composition.

Emulsions and Oily Materials

The composition according to the invention can optionally comprise one or more oils or other materials having the properties of an oil.

A composition in accordance with the invention may be formulated as an emulsion having both aqueous and oil phases. This applies particularly to leave-on products which are frequently formulated as emulsions. In an emulsion, an oil or oily material will normally be present, together with an emulsifier to provide either a water-in-oil emulsion or an oil-in-water emulsion, depending largely on the average hydrophilic-lipophilic balance (HLB) of the emulsifier employed.

Examples of suitable oils include mineral oils and vegetable oils, silicone oils and oily materials such as those already proposed herein as emollients.

The quantity of oil, if present, is often at least 5% by weight, often remains a minority of the composition, in other words 5 to 50% by weight. Preferred are at least 10% and/or not more than 30% by weight.

The oil or oily material, when present for the purposes for forming an emulsion, may form up to 90%, e.g. preferably from 10 to 80% by volume of the composition.

Emulsifier

The composition according to the invention can also optionally comprise one or more emulsifiers the choice of which will normally determine whether a water-in-oil or and oil-in-water emulsion is formed. Duplex emulsions, ie water-in-oil-in-water or oil-in-water-in-oil, can also be formed.

When a water-in-oil emulsion is required, the chosen emulsifier or emulsifiers should normally have an average HLB value of from 1 to 6. "When an oil-in-water emulsion is required, a chosen emulsifier or emulsifiers should have an average HLB value of >6.

Examples of suitable emulsifiers are set below in Table 1 in which the chemical name of the emulsifiers is given together with an example of a trade name as commercially available, and the average HLB value.

TABLE 1

Chemical Name Trade Name HLB Value of Emulsifier

Sorbitan trioleate Arlacel 85 1.8 Sorbitan tristearate Span 65 2.1 Glycerol monooleate Aldo MD 2.7

Glycerol monostearate Atmul 84S 2.8 Glycerol monolaurate Aldo MC 3.3 Sorbitan sesquioleate Sorbitan monooleate Sorbitan monostearate Cetyl dimethicone copolyol Poloxyethylene (2) stearyl ether Poloxyethylene sorbitol beeswax derivative PEG 200 dilaurate Sorbitan monopalmitate Polyoxyethylene (3.5) nonyl phenol PEG 200 monostearate

Sorbitan monolaurate PEG 400 dioleate

Polyoxyethylene (5) monostearate Ethofat 60-16 9.0 Polyoxyethylene (4) sorbitan monostearate Polyoxyethylene (4) lauryl ether Dimethicone copolyol Polyoxyethylene (5) sorbitan monooleate PEG 300 monooleate Polyoxyethylene (20) sorbitan tristearate Polyoxyethylene (20) sorbitan trioleate Polyoxyethylene (8) monostearate PEG 400 monooleate PEG 400 monostearate

Polyoxyethylene 10 monooleate Ethofat 0/20 12.2 Polyoxyethylene (10) stearyl ether Brij 76 12.4

Polyoxyethylene (10) cetyl ether Brij 56 12.9

Polyoxyethylene (9.3) octyl phenol Triton X-100 13.0 Polyoxyethylene (4) sorbitan monolaurate PEG 600 monooleate PEG 1000 dilaurate Polyoxyethylene sorbitol lanolin derivative Polyoxyethylene (12) lauryl ether PEG 1500 dioleate

Polyoxyethylene (14) laurate Arosurf HFL-714 14.8 Polyoxyethylene (20) sorbitan monostearate Tween 60 14.9 Polyoxyethylene 20 sorbitan monooleate Tween 80 15.0 Polyoxyethylene (20) stearate Myrj 49 15.0 Polyoxyethylene (20) stearyl ether Brij 78 15.3 Polyoxyethylene (20) sorbitan monopalmitate Tween 40 15.6 Polyoxyethylene (20) cetyl ether Brij 58 15.7

Triethanolamine stearate >16 Polyoxyethylene (25) oxypropy1ene monostearate G-2162 16.0 Polyoxyethylene (20) sorbitol monolaurate Tween 20 16.7 Polyoxyethylene (23) lauryl ether Brij 35 16.9 Polyoxyethylene (50) monostearate Myrj 53 17.9 PEG 4000 monostearate Pegosperse 4000

MS 18.7

The foregoing list of emulsifiers is not intended to be limiting and merely exemplifies selected emulsifiers which are suitable for use in accordance with the invention.

It is to be understood that two or more emulsifiers can be employed if desired.

The amount of emulsifier or mixtures thereof, to be incorporated in the composition of the invention, when appropriate is from 1 to 50%, preferably from 2 to 20% and most preferably from 2 to 10% by weight of the composition.

Retinoids

The composition for use according to the invention optionally can also comprise a retinoid, such as retinoic acid or retinol (Vitamin A) and/or derivative thereof, further to enhance the benefits to skin.

In addition to retinol itself, examples of derivatives of retinol include:

Retinyl acetate Retinyl butyrate Retinyl propionate Retinyl octanoate Retinyl laurate Retinyl palmitate Retinyl oleate Retinyl linoleate, and Retinyl linolenate.

The amount of retinoid, when present in the composition according to the invention is from 0.01 to 10% and preferably 0.1 to 5% by weight of the composition.

Tocopherol and Tocopheryl Esters

The composition for use according to the invention optionally can also comprise a tocopherol (vitamin E group) , as an antioxidant for the composition, and to limit oxidative damage to skin. The vitamin E group comprises α.-tocopherol, jβ-tocopherol, γ-tocopherol and δ- tocopherol. The composition according to the invention optionally can also comprise a tocopheryl ester, such as tocopheryl acetate.

The amount of a tocopherol, or ester thereof, when present in the composition according to the invention, is from

0.0001 to 20%, preferably from 0.0001 to 10% by weight of the composition.

Water

The composition of the invention can also comprise water, usually up to 90%, preferably from 5 to 80% by volume. Water can function as the cosmetically acceptable vehicle.

Preferred is that the vehicle contains water, or aqueous ethanol, in an amount which is a majority of the composition, that is to say over 50%. If ethanol is present, the amount will generally remain a minority of the composition, such as from 10 to 50%. Even when ethanol is included, the quantity of water will generally be substantial, amounting to a majority of the composition or nearly so, such as at least 40% of the composition. Surfactants

A composition for use in accordance with the invention may contain one or more surfactants notably at least 1% thereof, in addition to the hydroxy alkanoate derivatives, which are cosmetically acceptable and suitable for topical application to the skin. This applies particularly when the composition is a cleansing composition containing an acyl derivative of hydroxyalkanoate as surfactant. Such compositions may contain a co-surfactant, for example in an amount up to 30% by weight of the composition, preferably from 5% or 10% to 25% or 20% by weight.

A co-surfactant may assist in providing a good lather when the composition is used. Examples of possible skin cleansing surfactants are now given.

Anionic surfactant

The composition of the invention can comprise soap or a non-soap anionic surfactant which is preferably chosen from alkyl sulphate, alkyl ether sulphate, alkyl sulphonate, alkyl aryl sulphonate, olefin sulphonate, acyl sarcosinate, acyl tauride, acyl isethionate, nonoalkyl sulphosuccinate, dialkylsulphosuccinate, N-acylated a- amino acid, alkyl carboxylate, monoalkyl phosphate and dialkyl phosphate.

Specific examples of anionic surfactants include:

alkyl sulphates, such as sodium lauryl sulphate [eg. EMPICOL CX available from Albright & Wilson] , and triethanolaminde lauryl sulphate [e.g. EMPICOL TL40/T, available from Albright & Wilson] .

alkylether sulphates, such as sodium lauryl ether sulphate [eg. EMPICOL ESB70, available from Albright & Wilson] . alkyl sulphonates, such as sodium alkane (C₁₃_₁₈) sulphonate [eg. HOSTAPUR SAS 30, available from Hoechst]

alkylaryl sulphonates, such as sodium alkyl benzene sulphonate [eg. TEEPOL CM44, available from Shell] .

olefin sulphonates, such as sodium olefin sulphonate (C₅_ ₁₈) [eg. HOSTAPUR OS, available from Hoechst] .

acyl sarcosinates, having the structure: (51)

where R³ is chosen from C₆_₁₄ alkyl, and

M is a counterion chosen from alkali metals, ammonium and substituted ammonium such as alkanolammonium.

An example of an acyl sarcosinate having the structure (51) , is sodium lauryl sarcosinate [eg. HAMPOSYL L-95, available from Grace] .

acyl taurides, having the structure (52) :

O

R 4⁴-CI-N- (CH₂)₂S0₃M (52) CH,

where R⁴ is chosen from C₈_₁₈ alkyl

An example of an acyl tauride having the structure (52) is coconut methyl taurine [eg. FENOPEN TC 42, available from International Spaicalty Products] . acyl isethionates , having the structure (53 ) :

O R s⁵-C H -0- ( CH₂ ) ₂S0₃M ( 53 )

where R⁵ is chosen from C₈_₁₈ alkyl.

An example of an acyl isethionate having the structure (53) is sodium acyl isethionate [eg. JORDAPON Cl, available from Jordon] .

monoalkyl sulphosuccinates, having the structure (54) :

O

R⁶ .-0-C ii-CH CH-COOM (54)

S0₃M

where R >6 is chosen from C₁₀_₂₀ alkyl.

Examples of monoalkyl sulphosuccinates having the structure (54) include:

sodium lauryl sulphosuccinate [eg. EMPICOL SLL, available from Albright & Wilson] .

magnesium alkyl sulphosuccinate [eg. ELFANOL 616 Mg, available from AKZO] .

sodium lauryl ethoxysulphosuccinate [eg. EMPICOL SDD, available from Albright & Wilson] .

coconut monoethanolamide ethoxysulphosuccinate [eg. EMPICOL SGG] .

disodium lauryl polyglvcolether sulphosuccinate [eg. SURTAGENE S30, available from CHEM-Y] . polvethyleneglycol sulphosuccinate [eg. REWOPOL SBFA 30, available from REWO] .

dialkyl sulphosuccinates, having the structure (55) :

(55)

where R⁷ and R⁸ are the same or different, and are chosen from C₆_₁₄ alkyl.

An example of a dialkyl sulphosuccinate having the structure (55) is sodium dilauryl sulphosuccinate [eg. EMCOL 4500, available from Witco] .

acyl lactylates, having the structure (56)

O H O

R ,⁹-C I- (0-C I-CI)_n-OM (56)

where R⁹ is chosen from C₆_₁₆ alkyl,

and n is 1 or 2.

An example of an acyl lactylate having the structure (56) is decanoyl lactylate [eg. PATIONIC 122a, available from Patterson, CJ] .

N-acylated o.-amino acids, such as sodium lauroyl glutamate [eg. ACYLGLUTAMATE LS-11, available from Ajinomoto Co. Inc] .

alkyl ether carboxylates , such as C₁₂.₁₄0 (EO) ₄OCH₂C0₂Na [eg . AKYPO RLM 38 , available from Akzo] monoalkyl phosphates and dialkyl phosphates, such as dioctyl phosphate.

Cationic surfactant

The composition of the invention can also comprise a cationic surfactant. Suitable cationic surfactants are those with the structure (57) :

where R¹, R², R³ and R⁴ each represents alkyl or aryl groups, and X represents al halogen counterion.

Preferred cationic surfactants in accordance with structure (57) include:

Hexadecyl trimethyl ammonium chloride, such as Arquad 16, available from Akzo.

Dihydrogenated tallow dimethyl ammonium chloride, such as Arquad 2HT, available from Akzo.

Dodecyl benzyl dimethyl ammonium bromide, such as Amoxyl BR 1244, available from Seppic.

Cocoamidopropyl trimethyl ammonium chloride, such as Empigen CSC, available from Albright & Wilson. Amphoteric surfactant

The composition of the invention can also comprise an amphoteric surfactant . Suitable amphoteric surfactants are derivatives of aliphatic quaternary ammonium, phosphonium arid sulphonium compounds, wherein the aliphatic radicals contain from 8 to 18 carbon atoms, and may be straight chain or branched, and further contain an anionic water-solubilising group, such as carboxyl, sulphonate, sulphate, phosphate or phosphonate.

Preferred amphoteric surfactants include:

Alkyl betaines, having the structure (58) :

where R¹ is C^-^ alkyl.

An example of an alkyl betaine having the structure (58) is lauryldimethyl betaine [eg. EMPIGEN BB, available from Albright & Wilson] .

Alkylamidopropyl betaines, having the structure (59) :

An example of an alkylamidopropyl betaine having the structure (59) is cocamidopropy betaine [eg. TEGOBETAIN L7, available from Goldschmidt) .

Alkylamphoglvcinates or Alkylamphopropjonates having the structure (60)

R¹- (vC_Hιι,₂)/ ₂,OH (60:

where R¹¹ is chosen from H, CH₂COO^" and (CH₂)₂COO^~, and R¹¹¹ is chosen from CH₂COO^" and (CH₂)₂COO^~

Suitable examples of compounds (60) are cocoamphoglycinate (available from GAF) , and cocoamphopropionate.

Sultaines, having the structure (61) : .

where R² is chosen from C₁₂_₁₆ alkyl alkylamido groups.

An example of a sultaine having the structure (61) is cocamidopropylhydroxysultaine [eg. CYCLOTERIC BET-CS, available from Alcolac) .

The most preferred amphoteric surfactant are lauryl dimethyl betaine and cocamidopropyl betaine.

Such amphoteric surfactants can contribute to the foaming of the skin cleansing composition, while ameliorating the harshness of the anionic surfactant.

Nonionic surfactant

The composition of the invention can also comprise alkoxylated or glycosidic nonionic surfactant having an HLB of 8 or more. Above this value nonionics generally form clear isotropic solutions in combination with the other surfactants in the ranges defined above. Preferred nonionic surfactants are polyoxyethylene alkyl esters and polyoxyethylene alkyl ethers and alkyl polyglycosides .

A suitable example of a polyoxyethylene alkyl ester is that having the CTFA designation Polysorbate 80 which is a mixture of oleate esters of sorbitol and sorbitol anhydrides, condensed with approximately 20 moles of ethylene oxide. Also suitable is Polysorbate 20 which is a mixture of laurate esters or sorbitol and sorbitol anhydrides condensed with approximately 20 moles of ethylene oxide.

Polysorbate 80 and Polysorbate 20 are available commercially as TWEEN 80 and TWEEN 20 respectively, from ICI Americas.

Also suitable for use in the compositions of the invention is the polyethylene glycol ether of C₉__1]L alcohol with an average of 8 ethoxy units, which is available commercially as NONIDET LE-8T or as SYNPERONIC 91-8T, and the polyethylene glycol ether of C₁₂_₁₅ alcohol with an average of 9 ethoxy units which is available commercially as DOBANOL 25-9.

Particularly useful alkyl polyglycosides include the glycosides of glucose or glucose oligomers where the alkyl chain can be C₈.₁₆ and the average number of glucose units is 1 to 2. A suitable example is ORAMIX NS 10 which is the glucoside of C₁₀_₁₂ fatty alcohol with an average of about 1.5 glucose units.

Also suitable for use in compositions of the invention are high molecular weight silicone surfactants, such as a high molecular weight polymer of dimethyl polysiloxane with polyoxyethylene and/or polyoxypropylene side chains having a molecular weight from 10,000 to 50,000.

The dimethyl polysiloxane polymer is conveniently provided as a dispersion in a volatile siloxane, the dispersion comprising, for example, from 1 to 20% by volume of the polymer and from 80 to 99% by volume of the volatile siloxane. Ideally, the dispersion consists of a 10% by volume of the polymer dispersed in the volatile siloxane.

Examples of the volatile siloxanes in which the polysiloxane polymer can be dispersed include polydimethyl siloxane (pentamer and/or hexamer) .

A particularly preferred silicone surfactant is cyclomethicone and dimethicone copolyol, such as DC 3225C Formulation Aid available from DOW CORNING. Another is laurylmethicone copolyol, such as DC Q2-5200, also available from Dow Corning.-

The amount of silicone surfactant, when present in the composition will normally be up to 25%, preferably from 0.5 to 15% by weight of the emulsion.

Other Cosmetic Adjuncts

Examples of other cosmetic adjuncts which can optionally be employed in the composition for use according to the invention include preservatives, such as para-hydroxy benzoate esters; antioxidants, such as butyl hydroxy toluene; humectants, such as glycerol, sorbitol, 2- pyrrolidone-5-carboxylate, dibutylphthalate, gelatin, polyethylene, glycol, preferably PEG 200-600; buffers, such as lactic acid together with a base such as triethanolamine or sodium hydroxide; ceramides of synthetic, animal or plant origin; pseudoceramides; phospholipids; vitamins, such as 1,25 dihydroxy cholecalciferol; waxes, such as beeswax, ozokerite wax, paraffin wax, plant extracts, such as Aloe vera, cornflower, witch hazel, elderflower, cucumber, thickeners; activity enhancers; colourants; perfumes; and sunscreen materials such as ultrafine titanium dioxide and organic sunscreens such as p-aminobenzoic acid and esters thereof, ethylhexyl p-methoxycinnamate, 2-ethoxyethyl p- methoxycinnamate and butyl methoxydibenzoylmethane, and mixtures thereof .

In a further preferred composition, the hydroxy alklanoate derivative is combined with ceramides, pseudoceramides, polyol fatty acid polyesters, sterols, particularly cholesterol, galactosyldiacyl-glycerols, glycosphingolipids, fatty acids and esters thereof and mixtures thereof and other ingredients, such as mevalonic acid, hexadecylsuccinic acid monobehenyl ester ethoxylate (7.3 EO) and/or derivatives thereof to produce a liposomal dispersion.

A further preferred composition may also contain in combination with the hydroxy alkanoate derivative and optional additional ingredients disclosed above, an organic acid component chosen from hydroxy alkanoic acids, such as alpha, beta and omega hydroxyacids, especially glycolic acid, lactic acid, citric acid, tartaric acid, tartronic acid and 2-hydroxyoctanoic acid, and keto alkanoic acids, esters thereof and mixtures thereof.

Cosmetic adjuncts can form the balance of the composition,

_EH

The composition of the invention will normally have a pH value of from 4 to 9, preferably from 4.5 to 8.5. The pH can be adjusted as necessary by the addition of an alkali or acid as a pH adjustant, and/or by the addition of a buffer, such as a citrate buffer or a phosphate buffer. PRESERVATION OF THE COMPOSITION

The composition for use in accordance with the invention is preferably preserved against microbial attack in such a manner that it will enjoy an extended shelf life following manufacture and prior to sale and use. Ideally the composition will have an indefinite shelf life.

Examples of the methods that can be employed to achieve preservation of the composition, includes the following:

(i) Sterilisation

The composition according to the invention can be preserved by sterilisation to remove or kill substantially all viable microbial contaminants. This can be achieved for example by irradiation using a lethal dose of gamma rays, by heat sterilisation or by ultrafiltration using techniques that are well established in the pharmaceutical industry.

(ii) Chemical Preservative

The composition according to the invention can also be preserved by including in it a chemical preservative which functions to prevent the growth of or kill bacteria, fungi or other microorganisms .

Examples of chemical preservatives include ethanol, benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, sodium propionate and the methyl, ethyl, propyl and butyl esters of p-hydroxybenzoic acid. The amount of chemical preservative that can be incorporated in the composition according to the invention will generally be from 0.05 to 5%, preferably from 0.1 to 2% by weight, the amount chosen being sufficient to arrest microbial proliferation. (iii) Water activity depressants

The composition according to the invention can also be preserved by the inclusion of a water activity depressant such as glycerol, propylene glycol, sorbitol, sugars and salts, for examples alkali metal halides sulphates and carboxylates . When employing a water activity depressant, sufficient should be incorporated in the composition according to the invention to reduce the water activity (α._w) from 1 to < 0.9, preferably to < 0.85 and most preferably < 0.8, the lowest of these values being that at which yeasts, moulds and fungi will not proliferate.

PROCESS

The invention also provides a process for preparing a composition according to the invention which comprises the steps of mixing an effective amount of an hydroxy alkanoate derivative, as herein defined, together with a cosmetically acceptable carrier for the derivative.

Product Form and Container

The composition of the invention can be formulated as liquids, for example as a lotion, shampoo, milk or cream for use in conjunction with an a'pplicator such as roll- ball applicator, or a spray device such as an aerosol can containing propellant, or a container fitted with a pump to disperse the liquid product. Alternatively, the compositions of the invention can be solid or semi-solid, for example sticks, creams or gels, for use in conjunction with a suitable applicator or simply a tube, bottle or lidded jar, or as a liquid-impregnated fabric such as a tissue wipe.

The invention accordingly also provides a closed container containing a composition as herein defined. USE OF THE COMPOSITION

The acyl (and/or alkyl) derivatives of hydroxyalkanoate, when applied to the stratum corneum, will penetrate into the epidermis or cutaneous appendages, such as eccrine, apocrine and sebaceous glands, where hydrolysis by endogenous skin or microbial esterases will cleave the molecule to release in situ the corresponding hydroxy alkanoate, together with the fatty acid or fatty alcohol that forms the residue of the applied hydroxy alkanoate derivative.

As stated earlier, the composition as applied to the skin surface can either be a "leave-on" product or a "rinse- off" or "wipe-off" product. When the composition is a leave-on product, such as a cream or lotion, it can be applied to the skin from a ^'suitable container and spread over a desired area of skin, such as the face and neck, shoulders, arms and legs, and then rubbed in using the hands and fingers, or using an applicator. The hydroxyalkanoate derivative being lipophilic in nature, will penetrate into and through the stratum corneum, by virtue of the lipid materials that normally reside in that region close to the skin surface. On reaching the strata below the superficial stratum corneum cells, or penetration into the cutaneous appendages, esterases are encountered that hydrolyse the hydroxy alkanoate derivative to release the desired hydroxyalkanoate.

Repeated application of such leave-on products, for example at night and in the morning on a daily basis, will provide a continuous supply of hydroxyalkanoate to the epidermis, which will thereby benefit by its improving ability to retain moisture i.e. to become moisturised. Other attributes of the skin will also improve, particularly elasticity, disappearance of fine lines and wrinkles, and the skin will altogether become more healthy with improved tone and condition.

When the composition for use in accordance with the invention is a "rinse-off" product, it will generally function as a skin cleanser. A suitable amount, for example 5 to 10 ml of the skin cleanser comprising the hydroxy alkanoate derivative, which can itself have surfactant properties, but is preferably accompanied by a co-surfactant, is applied to the skin and formed into a lather in the presence of water. After cleansing the skin, surplus product is generally rinsed from the skin and the skin is then dried. The rinse-off product can also be used for washing the hair or for cleansing the entire body surface, for example in the shower.

Although when using a rinse-off cleansing product, it would be expected that little or no product would remain on the skin, we have surprisingly found that a significant amount of the hydroxy alkanoate derivative is retained by the skin after each successive wash. This enables the skin to retain moisture to a greater extent than with other "rinse-of" products.

For this reason a hydroxyalkanoate derivative in accordance with this invention might be included as part of a composition for washing dishes by hand, thereby to enhance its mildness.

When the composition is a wipe-off product, it will also generally function as a skin cleanser, especially for removing make-up. A suitable amount, for example 0.5 to 5ml of the skin cleanser comprising the hydroxy alkanoate derivative can be applied to the skin, particularly where make-up is to be removed, and rubbed-in. The area of treated skin can then be wiped with a cloth, tissue or with cotton wool to remove surplus of the composition together with make-up that has been loosened from the skin.

Particularly preferred examples of both "rinse-off" and "leave-on" products in accordance with the invention and those that are used as part of the normal shaving process, namely as a pre-shave product, or as an after-shave product . Both products in use are intended to moisturise or otherwise condition the skin, prior to or after shaving, so as to enhance the shaving process, and this can be achieved by delivery to the epidermis of an hydroxy alkanoate, in the manner described hereinbefore.

Shaving treatment products such as these can be employed either by men to remove unwanted facial hair or beard, or by women to remove unwanted hair from other parts of the body surface, particularly the legs. Wherever such products are used, they possess the ability to enhance the moisturisation of the skin, so improving its condition after the shaving process.

Because men's shaving products are used regularly, they can serve to provide regular delivery of hydroxyalkanoate to the skin.

According to a particularly preferred embodiment of this aspect of the invention, after-shave products contain as a cosmetically acceptable vehicle, more than about 85% by weight of ethanol and water. Additionally, such shaving products can contain other cosmetic adjuncts such as glycerine, perfume, perfume solubilisers to promote product clarity, vitamins and derivatives thereof such as vitamin E acetate and Vitamin A palmitate, thickeners such as Carbopol 980, triethanolamine and other adjuncts as conventionally used in pre- or after-shave products. EXAMPLES

Example 1. Synthesis of 2- (stearoyl) octanoic acid Stearic acid was dissolved under reflux in sodium-dried diethyl ether and oxalyl chloride added and further refluxed for 2 hours to complete the reaction to stearoyl chloride. Excess ether and oxalyl chloride were first removed by warm distillation, and then,last traces of oxalyl chloride were removed by pumping under vacuum.

2-hydroxy octanoic acid was dissolved in pyridine (potassium hydroxide dried) and chloroform (ethanol free, anhydrous sodium sulphate/Al₂) ₃ column dried) and then stearoyl chloride added rapidly to the 2-hydroxy octanoic acid solution and shaken vigorously. The reaction vessel was left for 60 hours with occasional shaking.

The whole reaction mixture^"was then dissolved in diethyl ether and transferred to a separating funnel at -10°C. The ether solution was washed free of pyridine/salts with four aliquots of 0.5N hydrochloric acid cooled to 0°C. The ether solution was then washed with three aliquots of ice cold distilled water before drying over anhydrous sodium sulphate.

The solvent was then carefully removed in a dry nitrogen stream with heating at 35°C. Further purification of the stearoyl 2-hydroxy octanoic acid was then achieved by chromatography on a gel column made up and eluted with petroleum spirit (boiling range 40-60°C) . Example 2

A similar reaction was carried out using lauryl (i.e. dodecanoyl) chloride. It was added to 2-hydroxyoctanoic acid in pyridine and dry chloroform over 1 hour at 0°C. The reaction mixture was stirred for one further hour at 0°C, then allowed to warm to 20°C and allowed to stand for 48 hours.

The product was extracted as in Example 1, then its solution in a small volume of ether was neutralised to pH 7 with sodium hydroxide solution at 0°C. The solution was frozen and freeze dried.

The nmr spectrum of the product in deuterochloroform corresponded with information in the literature.

A sample of this substituted octanoate was acidified, extracted into ether and converted to its methyl ester by reaction in diazo methane. This was subjected to glc. The material eluting from the glc column was identified by mass spectroscopy, which confirmed the expected molecular weight and also showed fragments corresponding to loss of CH₃0 and COOCH₃. Lauroyl fragments were also observed, confirming that the preparation had led to the intended 2- (dodecanoyloxy)octanoic acid of structure

The above preparation was also carried out using ¹⁴C radiolabelled 2-hydroxyoctanoic acid. The resulting radiolabeled 2- (decanoyloxy) octanoic acid had a specific activity of about 2.5μCi. mg^"1, which is about 900mCi. mole^-1. It was neutralised to its sodium salt and diluted to an aqueous solution with a concentration of 55.6mM, corresponding to 2.0 % by weight. Three pieces of full thickness skin, taken from pig ear, were cut to 4 x 4cm and pinned out on a polystyrene foam support. 30μl aliquots of the above solution were applied to four of the test pieces with a pipette and spread over the entire surface using the pipette tip. The fifth piece was left untreated.

After 15 minutes the first test piece was swabbed with dry cotton wool to remove excess liquid. Ten pieces of Desquame tape, available from Diastron, were applied to the skin and then removed. Each piece strips cells from the skin. The later pieces of tape thus strip cells from further into the skin than the earlier pieces.

Each strip of tape was placed in a scintillation vial with lml of phosphate buffer (pH 7) .

The other two pieces of skin were treated similarly, but the test solution was left on them for one hour, or two hours before drying with cotton wool and tape stripping.

At the end of the experiment, 10ml scintillation fluid was added to each vial, and the amount of radio label was determined (as disintegrations per minute) using a scintillation counter. These results are set out in the following table, and show penetration of the 2- (decanoyloxy) octanoate to a considerable depth into the skin.

In a similar experiment nine tape strips were taken after six hours . The first three strips were incubated in 3ml of phosphate buffer. The next three strips and the final three strips were likewise incubated. After 30 minutes the buffer solutions were spotted onto a thin-layer chromatography plate (bearing silica gel as the stationary phase) .

The plate was eluted with 80:20:2 hexane:ether:acetic acid mixture. The spots on the plate were detected and quantified by their emitted radiation. Each lane on the plate displayed two spots, one corresponding to hydrolysis products of the octanoate and a second spot corresponding to the substituted octanoate itself. The results (mean of five repeats) were: % of Total label

Tapes 1 to 3 Peak 1 8.1 Peak 2 91.9

Tapes 4 to 6 Peak 1 54.4 Peak 2 45.6

Tapes 7 to 9 Peak 1 99.5 Peak 2 0.5

These results show that hydrolysis of the 2- (dodecanoyloxy) octanoate had occurred in each instance, and had proceeded almost to completion for the material which had penetrated furthest into the skin.

Example 3

The dodecanoyl derivative of 2-hydroxy dodecanoic acid, incorporating ¹⁴C radiolabel, was prepared in analogous manner to the preceding example. It had specific activity of 4.17μCi. mg^" It was neutralised to its sodium salt of formula:

and a 56mM solution was tested on pig skin, taking tape strips after 15 minutes, 1 hour and 2 hours as in the previous example. The results, set out in the following table, again show penetration to considerable depth into the skin. For tapes numbered 4 onwards there was more radiolabel after 1 hour than after 15 minutes.

The final line in the table shows the amount of radiolabel removed onto the cotton wool used to remove liquid from the pig skin before taking tape strips.

The invention is further illustrated by the following examples of formulations.

Example 4 - Water-in-oil skin cream

Ingredients % w/w

Silicone oil 20.00 Sodium chloride 2.00

Sodium 2- (octanoyloxy) butanoate 1.00

Whitener 0.15

Preservatives 0.36

Sodium hydroxide 1.00 Water to 100.00 Example 5 - Water-in-oil skin cream

Ingredients % w/w

Silicones Whitener

Preservatives Perfume

Ammonium hydroxide 2- (Decanoyloxy) hexanoic acid Humectant

Ammonium chloride Water

Exam le 6 - Water-in-oil skin cream with sunscreens

Example 7 - Oil-in-water skin cream

Ingredients % w/w

Emulsifier 10.00

Silicone oil 8.00

Thickener 0.50

Whitener 0.10

Preservatives 0.10

2- (Octanoyloxy)butyric acid 2.00

Humectant 10.00

Evening primrose oil 2.00

Sunscreens 3.00

Bactericides 0.30

Triethanolamine 3.10

Water to 100.00

Example 8 - Face mask

Ingredients

Kaolin

Bentonite

Cetyl alcohol

Potassium 2- (tetradecanoyloxy) octanoate Glycerol

Methyl paraben

Potassium dodecyl sulphate

Perfume

Water

Example 9 - Cleansing Cream

Ingredients % w/w

Lanette wax SX 16.00 Mineral oil 20.00

Microcrystalline wax 3.00

Glycerol 5.00

Sodium 2- (isostearoyloxy) octanoate 1.00

Water 55.00 Perfume

Preservative

Example 10 - Cleansing Milk

Ingredients % w/w

Mineral oil 10.00

Cetyl alcohol ^' 0.50

Stearic acid 3.00 Sodium 2- (hexanoyloxy) octanoate 1.00

TEA 1.80

Water 83.7 Perfume Preservative

Example 11 - Cleansing Mousse

Ingredients % w/w

Sodium lauryl ether sulphate (28%) 18.00 Sodium cocoamidopropyl betaine 7.50

Sodium 2- (γ-linolenoyloxy) octanoate 1.00

Glycerol 10.00

Ethanol 5.00

Vitamin E acetate 0.10 Cremophore RH410 0.50

Redoderm LIS 80 1.00

Preservative 0.26 Ammonium hydroxide (29%) to pH 7.00 Colourant Perfume

Propane/Butane 3.00

Water to 100.00

Example 12 - Mild Facial Cleanser

Ingredients % w/w

TEA 2- (linoleoyloxy)octanoate 20.00

Glycerol 10.00 Sodium cocoyl isethionate 7.00

Cocamidopropyl betaine 4.00

Polyoxeyethylene (EO) 20 sorbitan monolaurate 3.00

Hydroxypropyl methylcellulose 0.20 Preservative 0.20

Perfume 0.10

Citric acid to pH 6.50

Water to 100.00 Example 13 - Liquid Soap

Ingredients % w/w

Potassium 2- (dodecanoyloxy)butanoate 15.00 Triethanolammonium N-lauroyl glutamate 9.00

Cocoamidopropyl betaine 4.00

Propyleneglycol hydroxy isostearate 1.00

Trisodium citrate 7.00

Preservative 0.26 Perfume 0.15 Triethanolamine to pH 7.00

Water to 100.00

Example 14 - Cleansing Beauty Bar

Ingredients % w/w

Sodium n-myristoyl dilactylate 15.00

TEA 2- (mandeloyloxy)octanoate 15.00 Sodium n-stearoyl aspartate 10.00

Glycerol 8.00

Diglycerol 1.00

Perfume 0.50

Preservatives 0.26 Colourant 0.10

Water to 100.00

Exam le 15 - Dee Cleansin Gel

Example 16 - Moisturising Lotion

Ingredients % w/w

Glycerol

TEA

TEA 2- (cocoamidopropanoyloxy(butanoate

Magnesium aluminium silicate Glyceryl monostearate

Mineral oil

Stearic acid

Cetyl alcohol

Cerasynt IP Silicone oil

Preservative

Perfume

Carbopol 934 (2%)

Water

Exam le 17 - Skin Cream

Exam le 18 - Dr Skin Cream

Example 19 - Barrier Cream

Ingredients % w/w

Stearic Acid 6.00 Cetyl alcohol 3.00

Lanolin 3.00

Soft paraffin 2.00

TEA 2- (n-octanoyloxy)butanoate 0.50

Sodium hydroxide 0.65 Kaolin 18.00 Perfume Colourant Preservative

Water to 100.00

Example 20 - Anti-ageing Eve Gel

Ingredients Glycerol

Potassium 2- (acetyloxy) octanoate

Vitamin E acetate

Aloe vera gel

TEA to pH 7.00 Carbopol 934 (2%)

Preservative

Perfume

Colourant

Water to 100.00 Example 21 - Aftershave Lotion

Ingredients % w/w

Ethanol Glycerin

Sodium 2- (iso-stearoyloxy)butanoate PEG hydrogenated castor oil Perfume Water

Exam le 22. Aftershave Gel

Example 23. Skin Cleansing Milk

Ingredients % w/w

PEG-20 Sorbitan Monostearate 1.80 Sorbitan monostearate 1.50

Mineral Oil 39.9

Butyl 2-hydroxyoctanoate 5.00

Triethanolamine 0.70

Stearic Acid 1.40 Porpylparaben 0.10

Polyethylene glycol 8.00

Methyl paraben 0.10

Ethylhydroxyethyl cellulose 0.54

Sorbic acid 0.002 Water to 100

Example 24. Dry Skin Cream

Ingredients % w/w Mineral Oil 5.00

Isostearyl 2-hydroxyhexanoate 3.00

Cerasin Wax 1.75

Petroleum jelly 4.50

Glyceryl monostearate 1.75 Candelilla Wax 1.00

Stearic acid 2.25

Cetyl alcohol 1.40

Isopropyl palmitate 6.00

Laureth 23 0.36 Sorbitan oleate 1.40

Propyl paraben 0.10

Glycerol 3.00

Triethanolamine 0.60

Methyl paraben 0.15 Carbopol CC-122 (2% dispersion) 10.0

Imidazolidinyl urea 0.20

Water to 100 Example 25 . Sunscreen

Ingredients % w/w

Propyl paraben 0.10 Dea-cetyl phosphate 1.00

Benzophenone-3/oxobenzone 6.00

PVP/eicosene copolymer 2.50

Stearic acid 4.00

Tocopherol acetate 0.10 Dimethicone 1.00

Stearyl 2-hydroxyoctanoate 1.50

Petroleum Jelly 0.25

Octyl methoxycinnamate ethylhexyl P-ME 7.50

Triethanolamine 1.40 DMDM hydantoin 0.25

Carbopol 2% dispersion 5.00

Magnesium aluminium silicate 0.20

Glycerol ^' 5.00

Methyl paraben 0.15 Aloe Vera Gel 0.05

Disodium EDTA 0.05

Simethicone 0.01

Cetyl alcohol 0.70

Octyl salicylate/2 ethylhexyl salicylate 5.00 Water to 100

Example 26. Moisturising Facial Cleanser

Ingredients % w/w

Mineral Oil 5.00

Lauryl 2-hydroxyoctanoate 4.00 Sorbitan stearate 1.50

Polysorbate 60 1.80

Methyl paraben 0.20

Propyl paraben 0.10

PEG 550 8.00 Triethanolamine 1.06

Stearic acid 1.40

BHT 0.05

Phenoxyethanol 0.40

Carbopol 2% dispersion 5.00 Glycerol 5.00

Water to 100

Example 27. Rinsable Cream Cleanser

Ingredients % w/w

Mineral Oil 30.00

Myristyl 2-hydroxydecanoate 10.00

Beeswax 2.30 Cerasin 0.50

Propyl paraben 0.10

PEG-16 soya sterol 5.00

PEG-8 dilaurate 2.00

Cetearyl alcohol 0.80 Behenic acid 0.80

Methyl paraben 0.15

Disodium EDTA 0.05

Sodium borate 0.80

Carpobol 2% dispersion 16.00 Water to 100 Example 28. Smoothing Shaving Foam

Ingredients % w/w Stearic acid 3.27

Palmitic acid^' 3.51

Laurie acid 0.76

Triethanolamine 3.01

Potassium hydroxide 0.28 Glycerol 4.61

Decyl 2-hydroxyoctanoate 1.30

Tween 20 0.96

Tocopherol acetate 0.05

Isostearyl lactylate 0.10 Silicone Fluid DC2-1865 1.50

Silicone Fluid DC193 0.77

CAP 48 4.00

Water to 100

The above formulation can be modified by replacing the ester of 2-hydroxyalkanoic acid with an equal amount of sodium 2-decyloxyoctanoate.

Example 29. Aftershave Balm

Ingredients % w/w Ethanol 60.0

Cetyl 2-hydroxyhexanoate 0.40 Glycerol 2.00 Perfume 0.40

Benzophenone-11 0.02 Water to 100

The above formulation can be modified by replacing the ester of 2-hydroxyalkanoic acid with an equal amount of sodium 2-octyloxyhexanoate.

Claims

1. The use of an effective amount of at least 0.001% by weight based on the total composition of a hydroxy alkanoate derivative having the structure (1) :

0 where R¹ represents H- or C_χH O_zN_w-C- R³ represents H-, C_xIL,0₂N_w- or a metallic, ammonium or alkanolammonium counterion, p is an integer from 2 to 22, q is an integer from 5 to 45, x is an integer of from 1 to 20, y is an integer of from 3 to 41, z is O, or an integer of from 1 to 10, w is O, or an integer of from 1 to 5, and m is an integer of from 1 to 5 provided that when R¹ is H-, then R³ is C_xH_y0₂N_w-, and when

O

R~ is H- or a counterion, then R^~ is C_XH O_zN_wC-

to deliver to the epidermis, as a moisturiser for the skin, the corresponding 2-hydroxyalkanoate having the structure (2) :

C H 0

I ^q II

HO-CH C - OX (2)

where X represents -H or a counterion;

in a composition intended for topical application to human skin; said compositions also comprising a cosmetically acceptable vehicle.

2. A method for delivering to the epidermis a 2-hydroxy alkanoate having the structure (2) :

where p is an integer of from 2 to 20, q is an integer of from 5 to 41, and X represents H-, or a counterion,

which comprises the steps of

i) applying topically to the skin a composition comprising the corresponding hydroxy alkanoate derivative having the structure (1) :

the values of R¹, R³, p, q, m and X being as defined in claim 1; provided that when R¹ is H-, then R³ is C_xH_y0₂N_w- , and when R³ is H- or a counterion,

0 then R¹ is C_xH_y0₂N_wC-

ii) leaving the composition in contact with the skin for at least 10 seconds to permit the hydroxy alkanoate derivative to penetrate through the stratum corneum to reach the lower strata of the epidermis, and

iii) cleaving the hydroxy alkanoate derivative in the epidermis by contact with esterases to provide the 2- hydroxy alkanoate.

3. A composition suitable for topical application to the skin, hair, nails, mucosae and other epithelial tissue, which composition comprises:

i) a hydroxy alkanoate derivative having the structure (1) :

ii) a cosmetically acceptable vehicle for the hydroxy alkanoate derivative;

the hydroxyalkanoate derivative possessing the ability of penetrating the stratum corneum and hydrolysing by enzymic cleavage within the epidermis to yield the corresponding hydroxyalkanoate having the structure (2) :

W~ °

HO-CH C - OX (2)

thereby to moisturise the epithelial tissue; the value of R¹, R³, p, q, m and X being as defined in claim 1.

4. The use, method or composition according to claim 1, 2 or 3 respectively, in which C_nH is an alkyl or alkenyl group such that q = 2p± 1.

5. The use, method or composition according to claim 4, in which the alkanoate derivative is an acyl hydroxy alkanoate where R¹ in structure (1) represents the acyl group

O

C_χH_y C- wherein C_xH_y is a straight or branched alkyl or alkenyl chain m is 1 to 5, and

R³ represents -H, or an alkali metal, an alkaline earth metal ammonium or an alkanolammonium counterion.

6. The use, method or composition according to claim 5, in which R¹ is an acyl group chosen from:

n-propionyl n-butanoy1 n-hexanoyl n-octanoyl n-decanoyl n-dodecanoyl n-tetradecanoyl n-hexadecanoyl n-octadecanoyl n-linoleoyl n-linolenoyl γ-linolenoyl n-arachidonoyl columbinoyl iso-butanoyl iso-hexanoy1 iso-octanoyl iso-octadecanoyl iso-butanoyl iso-octanoyl iso-octadecanoyl iso-dodecanoyl ethylglycoloyl leucoyl and mandeloyl.

7. The use, method or composition according to any one of claims 1 to 4, in which the hydroxyalkanoate derivative is an alkyl hydroxyalkanoate where R¹ in structure (1) represents H-,

R³ represents C_χH - , and m is 1.

8. The use, method or composition according to claim 7, in which the alkyl hydroxy alkanoate is chosen from:

methyl 2-hydroxybutanoate n-butyl 2-hydroxybutanoate n-hexyl 2-hydroxybutanoate n-octyl 2-hydroxybutanoate n-decyl 2-hydroxybutanoate n-dodecyl 2-hydroxybutanoate n-octadecyl 2-hydroxybutanoate ethyl 2-hydroxyhexanoate ethyl 2-hydroxyoctanoate, and n-dodecanyl 2-hydroxyoctanoate.

9. The use, method or composition according to any preceding claim, in which the amount of hydroxyalkanoate derivative present in the composition as an effective amount, is from 0.001 to 50%, preferably from 0.1 to 30%, and most preferably from 0.5 to 20% by weight of the composition.

10. The use, method or composition according to any preceding claim, in which the composition further comprises a penetration enhancer.

11. The use, method or composition according to any preceding claim, in which the composition further comprises a retinoid chosen from

retinyl acetate retinyl butyrate retinyl propionate retinyl octanoate retinyl laurate retinyl palmitate retinyl oleate retinyl linoleate, and retinyl linolenate, and/or further comprises tocopherol and/or a tocopheryl ester.

12. The use, method or composition according to any preceding claim, in which the composition is a leave-on product chosen from creams, lotions, milks, gels.

13. The use, method or composition according to any preceding claim, in which the composition is an emulsion containing both an aqueous phase and an oil phase.

14. The use, method or composition according to any preceding claim in which the cosmetically acceptable vehicle includes water or aqueous ethanol in an amount which is more than 50% by weight of the composition, the amount of ethanol, if any, not exceeding 50% by weight of the composition.

15. The use, method or composition according to any preceding claim in which the composition includes water- immiscible oil in an amount exceeding the amount of hydroxyalkanoate derivative.

16. The use, method or composition according to any of claims 1 to 7, in which the composition is a cleaning composition containing water and from 5 to 40% by weight of a said hydroxyalkanoate derivative of structure (1) wherein R³ represents -H, or a metallic, ammonium or alkanolammonium counterion while R¹ represents

17. The use, method or composition according to claim 16 in which the composition also contains from 5 to 30% by weight of one or more co-surfactants.

18. A method for cleaning the skin or the hair which comprises the steps of

(i) applying to the skin or hair cleansing composition as defined in claims 16 or 17; (ii) forming a lather on the skin or hair by massaging in the presence of added water, thereby to cleanse the skin or hair; and

(iii) subsequently rinsing the lather from the skin or hair with water.