WO1992006982A1

WO1992006982A1 - Cosmetic composition

Info

Publication number: WO1992006982A1
Application number: PCT/GB1991/001839
Authority: WO
Inventors: Peter Critchley; Susan Edith Kirsch; Anthony Vincent Rawlings; Ian Richard Scott
Original assignee: Unilever Plc; Unilever Nv
Priority date: 1990-10-22
Filing date: 1991-10-21
Publication date: 1992-04-30
Also published as: EP0555250A1; BR9107032A; JPH06504265A; AU8734391A; CA2094500A1; KR930702360A

Abstract

Modified pseudoceramides are defined, together with their synthesis and compositions comprising them for topical application to human skin, hair and nails. The modified pseudoceramides have a structure given by (I) or (II) and an approximate summary is that R?1, R4, R5¿ are aliphatic hydrocarbon, A is H or an aliphatic group terminated by OR3 and at least one R2 or R3 is phosphate or sulphate. The presence of phosphate or sulphate facilitates skin absorption, after which the phosphate or sulphate is removed by enzymes naturally present in vivo.

Description

COSMETIC COMPOSITION

FIELD OF THE INVENTION

The invention relates to modified pseudoceramides,

their synthesis and use in compositions for topical application to human skin, hair or nails.

BACKGROUND TO THE INVENTION AND PRIOR ART It is generally understood that ceramides present within the intercellular lipid lamellae of the stratum corneum play an important role in the production and maintenance of the water permeability barrier of the skin. Ceramides, or substances closely related to them, have been disclosed as components of skin care compositions. In particular, Kao Corporation in EP 227 994 and EP 282 816 disclose the use of synthetic ceramides, which are similar to their to their natural counterparts found in skin. Also, Unilever in EP 97 059 disclose ω -O-linoleoyl ceramides and emphasize their role in the water barrier function of the skin.

It is believed that one of the causes of dry skin and ageing skin is a reduction in the amount of lipid

contained within these intercellular lipid lamellae. It is therefore desirable to be able successfully to replace these depleted lipids via the topical route.

One of the problems associated with the topical

application of skin and hair care products containing ceramides or their synthetic analogues, is devising a suitable method for delivering them effectively to the lipid lamellae, without causing permanent disruption of the stratum corneum. It is accordingly apparent that permanently disrupted stratum corneum is unable to retain molecules of this sort, as they are simply washed out again when the stratum corneum (skin) is contacted with water.

This problem has not successfully been solved to date. Kao Corporation have reported in GB 2 178 312, EP 227 994 and EP 282 816, that co-surfactants such as glyceryl ethers assist synthetic ceramide to penetrate into the stratum corneum. However, these co-surfactants tend to disrupt the stratum corneum, so that when penetration occurs allowing the synthetic ceramide access to the lipid lamellae, there is nothing to prevent them being washed out again on contact with water.

We have solved this problem by using modified

pseudoceramides, that is synthetic analogues of naturally occuring ceramides which resemble in the key properties the natural substances, and which have been modified by phosphorylation and/or sulphation. Accordingly, when these modified pseudoceramides are applied topically to the skin, together with a suitable cosmetically acceptable vehicle, they will readily penetrate the stratum corneum without permanently disrupting it, and after

demodification with phosphatases or sulphatases which occur naturally in skin and which will cleave off the phosphate or sulphate groups respectively, the unmodified pseudoceramide structures will remain locked in the desired location within the stratum corneum. Since the phosphate and/or sulphate groups, which facilitate

delivery, have been removed once the pseudoceramide is in position, it is then not be possible subseguently to wash the pseudoceramide from the skin, so ensuring that it is available to effect repair in situ of lipid lamellae which have become damaged under dry skin conditions. SUMMARY OF THE INVENTION

We have modified pseudoceramides by phosphorylation or sulphation to assist their penetration into the lipid lamellae of the stratum corneum. Once located within the lipid lamellae, naturally-occurring phosphatases and sulphatases will cleave off the phosphate or sulphate groups respectively, to leave the pseudoceramides lodged firmly within the stratum corneum. DEFINITION OF THE INVENTION

Accordingly, the invention provides modified

pseudoceramides having the structure (1): (1)

where R represents the group:

R⁴-C- , or the group

R⁵-O-CH₂CH CH₂- ;

OR² R¹ represents a linear or branched, saturated or unsaturated, hydroxylated or

non-hydroxylated, phosphorylated or non-phosphorylated, sulphated or non-sulphated aliphatic hydrocarbon having from 1 to 49 carbon atoms; A represents H or the group:

(2)

R² & R³ individually represent H, a sugar

residue, a phosphate residue (P_i), or a sulphate residue (SO₃ ^Θ); R⁴ represents a linear or branched,

saturated or unsaturated, hydroxylated or non-hydroxylated, phosphorylated or non-phosphorylated, sulphated or

non-sulphated aliphatic hydrocarbon group having from 1 to 49 carbon atoms or the group Y-O-(C_aH_b)- ;

R⁵ represents a linear or branched, saturated or unsaturated, hydroxylated or non- hydroxylated, phosphorylated or non- phosphorylated, sulphated or non-sulphated aliphatic hydrocarbon group having from 1 to 49 carbon atoms;

P _i represents

a is an integer of from 7 to 49

b is an integer of from 10 to 98

c is 0, or an integer of from 1 to 4

n is 0 or 1

X¹, X² & X³ individually represent H, a C_{1 to 5}

alkyl group or a C_{1 to 5} hydroxyalkyl group

Y represents H or a residue of a C₁₄ to C₂₂ fatty acid having the structure (3):

-C-(C_xH_yZ_z)CH₃ (3) where Z is -OH, -OP_i, -OSO₃ ^Θ or an epoxy oxygen x is an integer of from 12 to 20

y is an integer of from 20 to 40

z is O, or an integer of from 1 to 4; provided that at least one out of R² & R³ is either a phosphate residue or a sulphate residue. DISCLOSURE OF THE INVENTION

The Modified Pseudoceramide

The invention provides a class of modified

pseudoceramides having the general structure (1) or (2) as hereinbefore defined.

The group R¹ of the structure (1) above may preferably be aliphatic hydrocarbon group of 1 to 33 carbon atoms, more preferably 8 to 28 carbon atoms, yet more preferably 12 to 22 carbon atoms.

The group R⁴ is preferably an aliphatic hydrocarbon group of 8 to 49 carbon atoms, more preferably 11 to 29 carbon

If

atoms (so that R⁴ C is acyl of 12 to 30 carbon atoms). The group R⁴ may be derived from a hydroxylated aliphatic group and may be sulphated or phosphorylated through reaction with the hydroxyl group(s).

The group R⁵ is preferably aliphatic hydrocarbon of up to 28 carbon atoms, especially 8 to 28 carbon atoms, more preferably 12 to 22 carbon atoms. Also, with reference to structure (1), the value of "a" is preferably an integer of from 24 to 30 and the value of "b" is preferably an integer of from 44 to 60. Also, with reference to structure (1), the group Y

preferably represents a straight chain saturated C_16-18 fatty acid residue or a straight chain all cis n-6,9 di-unsaturated C_16-18 fatty acid residue. Specific examples of these modified pseudoceramides and related structures are those having the structures

(4)-(20):

N-(2-hydroxy-3-hexadecyloxypropyl)-N-(2-phosphoethyl) hexadecamide having the structure (4):

(4)

N-(2-hydroxyoctadecyl)-N-(2-sulphoethyl)hexadecamide having the structure (5):

(5)

N-(2-hydroxy-3-hexadecyloxypropyl)-N-(2-phosphoethyl)- ω -o-linoleoyl docosamide having the structure (6):

(6) linoleoyl-O-(

N-(2-hydroxy-3-hexadecyloxypropyl)-N-(2-sulphoethyl)- ω)-O-linoleoyl hexadecamide having the structure (7):

(7) linoleoyl-O-(CH

N-(2-hydroxyoctadecyl)-N-(2-phosphoethyl)-ω-O-linoleoyl- hexadecamide having the structure (8):

(8) linoleoyl-O-(CH₂)₁₅

N-(2-hydroxy-3-nonyloxypropyl)-N-(2-sulphoethyl)decamide having the structure (9):

(9)

N-(2-hydroxy-3-tritriacontyloxypropyl)-N-(2-phosphoethyl) pentacosamide having the structure (10):

(10)

N-(2-hydroxy-3-hexadecyloxypropyl)-N-(3-methyl-4- phosphobutyl)hexadecamide having the structure (11) :

(11)

N-(2-phospho-3-hexadecyloxypropyl)-N-(2-phosphoethyl) hexadecamide having the structure (12):

(12)

N-(2-0-glucopyranosyl-3-hexadecyloxypropyl)-N-(2- phosphoethyl)hexadecamide having the structure (13):

(13)

N-(2-phospho-3-hexadecyloxypropyl)-N-(2-hydroxyethyl)- hexadecamide having the structure (14):

(14)

N-(2-sulphooctadecyl)-N-(2-hydroxyethyl)hexadecamide having the structure (15):

(15)

N-(2-sulpho-3-hexadecyloxypropyl)-N-(2-sulphoethyl)- hexadecamide having the structure (16):

(16)

N-(2-sulpho-3-hexadecyloxypropyl)-N-(2-phosphoethyl)- hexadecamide having the structure (17):

(17)

N-(2-phospho-3-hexadecyloxypropyl)-N-(2-phosphoethyl)-2- phosphohexadecamide having the structure (18):

N-(2-sulpho-3-tritriacontyloxypropyl)-N-(2-sulphoethyl)-2- sulphopentacosamide having the structure (19):

N-(2-phospho-3-hexadecyloxypropyl)-N-(2-phosphoethyl)- linoleamide having the structure (20):

CH₃ (CH₂ )₄ CH=CHCH₂CH=CH(C

N-(2-sulpho-3-pentadecyloxypropyl)-N-(2-sulphoethyl)- linoleamide having the structure (21):

CH₃ (CH₂ )₄CH=CHCH₂CH=CH(

2-Phosphoethanolamine-N-bis-(2-phospho-3- hexadecyloxypropyl) having the structure (22) :

(22)

2-phosphoethanolamine-N-bis-(2-sulpho-3- hexadecyloxypropyl) having the structure (23) :

(23)

Di-(2-sulpho-3-hexadecyloxypropyl)amine having the structure (24):

(24)

SYNTHESIS OF THE MODIFIED PSEUDOCERAMIDES

The modified pseudoceramides according to the invention can be synthesised using a conventional method involving phosphorylation and/or sulphation. Examples of

phosphorylation comprise the treatment of pseudoceramide with one of the following: (i) phosphorus pentoxide - (P₂O₅),

(ii) polyphosphonic acid,

(iii) phosphorus oxychloride, (POCl₃), followed by hydrolysis, or

(iv) phosphorus trichloride (PCl₃) followed by:

(a) oxidation using, for example,

chlorine, and then

(b) hydrolysis.

Examples of sulphation comprise the treatment of

pseudoceramide with one of the following: (i) chlorosulphonic acid,

(ii) thionylchloride, (SOCl₂), or

(iii) fuming sulphuric acid The material which is subjected to sulphation or

phosphorylation will preferably be of formula

in which A is H or a group

- ( CH₂ )_c

and other characteristics are as set out above.

Phosphorylation or, as the case may be, sulphation will preferably be carried out under conditions where any hydroxyl group present in the starting material can react. This then leads to (at least some) formation of product compounds in which neither R² nor R³ is H. It can also convert hydroxyl groups present as substituents on R¹, R⁴ or R⁵ into phosphate or sulphate groups. There may be sulphation or phosphorylation of all free hydroxyl groups in the starting material. Such uncontrolled sulphation or phosphorylation is acceptable because it is intended that the sulphate or phosphate groups will be removed in vivo by naturally occurring enzymes. SPECIFIC EXAMPLES OF THE SYNTHESIS

Synthesis of N-(2-phospho-3-hexadecyloxypropyl)-N- ( 2-phosphoethyl)-hexadecamide (12) The phosphorylated pseudoceramide having the structure (12) is prepared from N-(2-hydroxy-3-hexadecyloxypropyl) -N-(2-hydroxyethyl)-hexadecamide, having the structure (25), in accordance with the following scheme:

(25)

(12)

Synthesis of N-(2-sulpho-3-hexadecyloxypropyl)-N- (2-sulphoethyl) hexadecamide (16)

The sulphated pseudoceramide having the structure (16) is prepared from N-(2-hydroxy-3-hexadecyloxypropyl)

-N-(2-hydroxyethyl)-hexadecamide, having the structure (25), in accordance with the following scheme:

(25)

3

(16)

DEFINITION OF COMPOSITIONS OF THE INVENTION

The invention also provides a composition for topical application to human skin which comprises: i. an effective amount of a modified pseudoceramide or mixture of modified pseudoceramides having the structure (1); and ii. a cosmetically acceptable vehicle for the modified pseudoceramide.

DISCLOSURE OF THE COMPOSITION The composition according to the invention comprises in its simplest form a special modified pseudoceramide or a mixture of pseudoceramides and a vehicle therefor to enable the modified pseudoceramide(s) to be dispersed onto the skin and distributed thereon.

The Modified Pseudoceramide

The composition according to the invention comprises an effective amount of a modified pseudoceramide, or a mixture thereof, having the structure (l) as herein defined.

Preferred examples of the modified pseudoceramide having the structure (1) are those having the structure (4) to (24), as herein defined.

The amount of the modified pseudoceramide, or a mixture thereof present in the composition according to the invention is from 0.00001 to 50%, preferably from 0.001 to 20% and most preferably from 0.1 to 10% by weight. The Cosmetically Acceptable Vehicle

The composition according to the invention also comprises a cosmetically acceptable vehicle to act as a dilutant, dispersant or carrier for the modified pseudoceramide in the composition, so as to facilitate its distribution when the composition is applied to the skin and/or hair.

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, glyceryl monostearate, 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, tallow, lard, olive oil, palm kernel oil, rapeseed oil, safflower seed oil, evening primrose oil, soybean oil, sunflower seed oil, avocado oil, olive oil, sesame seed oil, coconut oil, arachis oil, castor oil, acetylated lanolin alcohols, petroleum jelly, mineral oil, butyl myristate, isostearic acid, palmitatic acid, isopropyl linoleate, lauryl

lactate, myristyl lactate, decyl oleate, myristyl

myristate;

Propellants, such as trichlorofluoromethane,

dichlorodifluoromethane, dichlorotetrafluoroethane, monochlorodifluoromethane, trichlorotrifluoroethane, 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.

The cosmetically acceptable vehicle will usually form from 10 to 99.9%, preferably from 50 to 99% by weight of the emulsion, and can, in the absence of other cosmetic adjuncts, form the balance of the composition.

OPTIONAL SKIN BENEFIT MATERIALS AND COSMETIC ADJUNCTS A particularly convenient form of the composition

according to the invention is an emulsion, in which case 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-lyophilic balance (HLB) of the emulsifier employed. Oil or oily material

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

Examples of suitable oils include mineral oil and

vegetable oils, and oil materials, such as those already proposed herein as emollients. Other oils or oily materials include silicone oils, both volatile and non-volatile, such as polydimethyl siloxanes.

The oil or oily material, when present for the purposes for forming an emulsion, will normally form up to 90%, 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.

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 Arlacel 83 3.7 Sorbitan monooleate Arlacel 80 4.3 Sorbitan monostearate Arlacel 60 4.7 Poloxyethylene (2)

stearyl ether Brij 72 4.9

Poloxyethylene sorbitol

beeswax derivative G-1702 5 PEG 200 dilaurate Emerest 2622 6.3 Sorbitan monopalmitate Arlacel 40 6.7 Polyoxyethylene (3.5)

nonyl phenol Emulgen 903 7.8 PEG 200 monostearate Tegester PEG

200 MS 8.5

Sorbitan monolaurate Arlacel 200 8.6 PEG 400 dioleate Tegester PEG

400-DO 8.8

Polyoxyethylene (5)

monostearate Ethofat 60-16 9.0 Polyoxyethylene (4) sorbitan

monostearate Tween 61 9.6

Polyoxyethylene (4) lauryl

ether Brij 30 9.7 Polyoxyethylene (5) sorbitan

monooleate Tween 81 10.0 PEG 300 monooleate Neutronyx 834 10.4 Polyoxyethylene (20)

sorbitan tristearate Tween 65 10.5 Polyoxyethylene (20)

sorbitan trioleate Tween 85 11.0 Polyoxyethylene (8)

monostearate Myrj 45 11.1 PEG 400 monooleate Emerest 2646 11.7 PEG 400 monostearate Tegester PEG 400 11.9 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 Tween 21 13.3 PEG 600 monooleate Emerest 2660 13.7 PEG 1000 dilaurate Kessco 13.9

Polyoxyethylene sorbitol

lanolin derivative G-1441 14.0 Polyoxyethylene (12)

lauryl ether Ethosperse LA -12 14.4 PEG 1500 dioleate Pegosperse 1500 14.6

Polyoxyethylene (14)

laurate Arosurf HFL-714 14.8 Polyoxyethylene (20)

sorbitan monostearate Tween 14.9 Polyoxyethylene 20 sorbitan

monooleate Tween 80 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 Polyoxyethylene (25)

oxypropylene G-2162 16.0 monostearate

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.

Water

The composition of the invention can also comprise water, usually up to 98%, preferably from 5 to 80% by volume. Silicone Surfactant

The composition of the invention can also optionally comprise a high molecular weight silicone surfactant which can also act as an emulsifier, in place of or in addition to the optional emulsifier (s) already mentioned.

The silicone surfactant is a high molecular weight polymer of dimethyl polysiloxane with polyoxyethylene and/or polyoxypropylene side chains having a molecular weight of from 10,000 to 50,000 and having the structure:

where the groups R' and R" are each

chosen from -H, C_1-18 alkyl and

- [CH₂CH₂O]_a[CH₂CHO]_bH

CH₃ a has a value of from 9 to 115,

b has a value of from 0 to 50,

x has a value of from 133 to 673,

y has a value of from 25 to 0.25.

Preferably, the dimethyl polysiloxane polymer is one in which: a has a value of from 10 to 114

b has a value of from 0 to 49

x has a value of from 388 to 402

y has a value of from 15 to 0.75 one of groups R' and R" being lauryl, and the other having a molcular weight of from 1000 to 5000.

A particularly preferred dimethyl polysiloxane polymer is one in which: a has the value 14

b has the value 13

x has the value 249

y has the value 1.25

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 conventional adjuncts which can optionally be employed include preservatives, such as para-hydroxy benzoate esters; antioxidants, such 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; surfactants, such as glycerol ethers and other pseudoceramides of synthetic, animal or plant origin; phospholipids; 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 modified

pseudoceramide is combined with conventional ceramides, unmodified pseudoceramides, cholesterol, cholesterol fatty acids, fatty acids, triglycerides, cerebroside,

phospholipid and other ingredients well known to those skilled in the art to produce a liposomal dispersion.

In yet another preferred composition, the modified pseudoceramide is dissolved in squalene or squalane, optionally together with conventional ceramides and/or pseudoceramides, and formulated with volatile and

non-volatile silicones to produce an anhydrous or nearly anhydrous single phase system. Cosmetic adjuncts can form the balance of the composition.

Use of the Composition

The composition according to the invention is intended primarily as a product for topical application to human skin, especially as an agent for reducing the permeability to water of the skin, particularly when the skin is dry or damaged, in order to reduce moisture loss and generally to enhance the quality of skin. The composition can also be applied to hair and nails.

The modified pseudoceramides according to the invention have surfactant properties and can therefore also be used, in the form of a composition as herein defined, for cleansing the surface of the human body. In particular the composition can be used to cleanse the skin to remove make up or can be employed in a shampoo for cleansing the hair. In use, a small quantity of the composition, for example from 1 to 5ml, is applied to exposed areas of the skin, from a suitable container or applicator and, if necessary, it is then spread over and/or rubbed into the skin using the hand or fingers or a suitable device. PRODUCT FORM AND PACKAGING

The topical skin, hair or nail treatment composition of the invention can be formulated as a lotion having a viscosity of from 4,000 to 10,000 mPas, a fluid cream having a viscosity of from 10,000 to 20,000 mPas or a cream having a viscosity of from 20,000 to 100,000 mPas, or above. The composition can be packaged in a suitable container to suit its viscosity and intended use by the consumer.

For example, a lotion or fluid cream can be packaged in a bottle or a roll-ball applicator or a propellant-driven aerosol device or a container fitted with a pump suitable for finger operation. When the composition is a cream, it can simply be stored in a non-deformable bottle or squeeze container, such as a tube or a lidded jar.

The invention accordingly also provides a closed container containing a cosmetically acceptable composition as herein defined.

EXAMPLES

The invention is illustrated by the following examples. Example 1

This example illustrates a high internal phase

water-in-oil emulsion in accordance with the invention.

A high internal phase water-in-oil emulsion having the following formulation was prepared:

% w/w Fully hydrogenated coconut oil 3.9

Phosphorylated pseudoceramide

having the structure (14) 0. 1

Brij 92* 5

Bentone 38 0. 5

Preservative 0. 3

MgSO₄7H₂O 0. 3

Butylated hydroxy toluene 0. 01

Perfume qs

Water to 100

*Brij 92 is polyoxyethylene (2) oleyl ether

Example 2 This example also illustrates a high internal phase water-in-oil emulsion in accordance with the invention in which the formulation of Example 1 was prepared but with the following changes: i. liquid paraffin replaced the fully hydrogenated

coconut oil, and ii. the sulphated pseudoceramide had the structure (5). Example 3

This example also illustrates a high internal phase water-in-oil emulsion in accordance with the invention in which the formulation of Example 1 was prepared but with the following changes:

The phosphorylated pseudoceramide had the structure (6).

Example 4

This example illustrates an oil-in-water cream containing an ester of the invention.

An oil-in-water cream emulsion having the following formulation was prepared:

% w/w

Mineral oil 4

Sulphated pseudoceramide

having the structure (7) 0.1

Brij 56* 4

Alfol 16RD* 4

Triethanolamine 0.75

Butane-1,3-diol 3

Xanthan gum 0.3

Preservative 0.4

Perfume qs

Butylated hydroxy toluene 0.01

Water to 100

*Brij 56 is cetyl alcohol POE (10)

Alfol 16RD is cetyl alcohol Example 5

This example also illustrates an oil-in-water emulsion in accordance with the invention, in which the formulation of example 4 was prepared but with the following change: the modified pseudoceramide was phosphorylated and had the structure (8), as herein defined.

Example 6

This example also illustrates an oil-in-water emulsion in accordance with the invention, in which the formulation of example 4 was prepared but with the following changes: sulphated pseudoceramide was that having the

structure (9) as herein defined.

Example 7

This example illustrates an alcoholic lotion containing an amide of the invention.

The lotion had the following formulation: % w/w Phosphorylated pseudoceramide

having the structure (10) 0.2

Ethanol 40

Perfume qs

Butylated hydroxy toluene 0.01

Water to 100 Example 8

The lotion had the following formulations: % w/w Phosphorylated pseudoceramide

having the structure (11) 0.2

Dimethylsulphoxide 10

Ethanol 40

Antioxidant 0.1

Perfume qs

Water to 100

Examples 9 and 10 The following compositions according to the invention represent lotions which can be used in the treatment of dry skin: % w/w

9 10

Phosphorylated pseudoceramide

having the structure (12) 1.5 -

Phosphorylated pseudoceramide

having the structure (1133)) - 0 .5

Perfume 0. 1 0. 1

Hydroxyethyl cellulose 0. 4 0. 4

Absolute ethanol 25 25 p-methyl benzoate 0.2 0.2 Sterilised demineralised water to 100 to 100 Examples 11 and 12

The following compositions according to the invention represent lotions which can be used in the treatment of dry skin:

% w/w

11 12 The phosphorylated pseudoceramide

having the structure (14) 0.08 - The sulphated pseudoceramide

having the structure (15) - 0.15 Ethanol 10 10 Perfume 0.5 0.5

Distilled water to 100 to 100

Example 13 This example illustrates a high internal phase

water-in-oil emulsion in accordance with the invention.

% w/w

Fully hydrogenated coconut oil 3.9

sulphated pseudoceramide

having the structure (16) 0.1

Brij 92* 5

Bentone 38 0.5

Preservative 0.3

MgSO₄7H₂O 0.3

Butylated hydroxy toluene 0.01

Perfume qs

Water to 100

*Brij 92 is polyoxyethylene (2) oleyl ether

Example 14

This example also illustrates a high internal phase water-in-oil emulsion in accordance with the invention in which the formulation of Example 1 was prepared but with the following changes: i. liquid paraffin replaced the fully hydrogenated

coconut oil, and ii. the phosphorylated and sulphated pseudoceramide had the structure (17). Example 15

The phosphorylated pseudoceramide had the structure (22).

Example 16

An oil-in-water cream emulsion having the following formulation was prepared:

% w/w

Mineral oil 4

Phosphorylated and sulphated

pseudoceramide having

the structure (23) 0.1

Brij 56* 4

Alfol 16RD* 4

Triethanolamine 0.75 Butane-1,3-diol 3

Xanthan gum 0.3

Preservative 0.4

Perfume qs

Butylated hydroxy toluene 0.01 Water to 100

*Brij 56 is cetyl alcohol POE (10)

Alfol 16RD is cetyl alcohol Example 17

This example also illustrates an oil-in-water emulsion containing an ester of the invention, in which the formulation of example 4 was prepared but with the following change: the sulphated pseudoceramide was that having structure (24), as herein defined. Example 18

This example also illustrates an oil-in-water emulsion in accordance with the invention, in which the formulation of example 4 was prepared but with the following changes: the modified pseudoceramide was phosphorylated and had the structure (4) as herein defined. Example 19

This example illustrates an alcoholic lotion containing an amide of the invention. The lotion had the following formulation: % w/w

Sulphated pseudoceramide

having the structure (5) 0.2

Ethanol 40

Perfume qs

Butylated hydroxy toluene 0.01

Water to 100

Example 20

This example illustrates an alcoholic lotion containing an amide of the invention which is suitable for application to nails.

The lotion had the following formulations :

% w/w

Phosphorylated pseudoceramide

having the structure (6) 0.2

Dimethylsulphoxide 10

Ethanol 40

Antioxidant 0.1

Perfume qs

Water to 100

Examples 21 and 22

The following compositions according to the invention represent lotions which can be used in the treatment of dry, unmanageable hair. % w/w

21 22 Sulphated pseudoceramide

having the structure (7) 1.5 - Phosphorylated pseudoceramide

having the structure (8) - 0. 5 Perfume 0. 1 0. 1 Hydroxyethyl cellulose 0. 4 0. 4 Absolute ethanol 25 25 p-methyl benzoate 0. 2 0.2 Sterilised demineralised water to 100 to 100 Examples 23 and 24

The following compositions according to the invention represent lotions which can be used in the treatment of dry skin, hair or nails: % w/w

21 24

The sulphated pseudoceramide

having the structure (9) 0.08 -

The phosphorylated pseudoceramide

having the structure (10) - 0. 15

Ethanol 10 10

Perfume 0.5 0.5 Distilled water to 100 to 100 Example 25

The oil-in-water emulsion of Example 24 was prepared, but the sulphated pseudoceramide (7) was replaced with the phosphorylated pseudoceramide (18) or the phosphorylated pseudoceramide (20).

Example 26 The water-in-oil emulsion of Example 1 was prepared, but the phosphorylated pseudoceramide (14) was replaced with the sulphated pseudoceramide (21).

Claims

CLAIMS 1. Modified pseudoceramides having the structure (1):

(1)

A where R represents the group:

group ;

R¹ represents a linear or branched, saturated or unsaturated, hydroxylated or

non-hydroxylated, phosphorylated or non-phosphorylated, sulphated or

non-sulphated aliphatic hydrocarbon having from 1 to 49 carbon atoms; A represents H or the group:

(2)

R² & R³ individually represent H, a sugar

residue, a phosphate residue (P_i), or a sulphate residue (SO₃ ^Θ);

R⁴ represents a linear or branched,

saturated or unsaturated, hydroxylated or non-hydroxylated, phosphorylated or non-phosphorylated, sulphated or non-sulphated aliphatic hydrocarbon group having from 1 to 49 carbon atoms or the group Y-O-(C_aH_b)- ; R⁵ represents a linear or branched,

saturated or unsaturated, hydroxylated or non-hyroxylated, phosphorylated or non-phosphorylated, sulphated or non- sulphated aliphatic hydrocarbon group having from 1 to 49 carbon atoms; P_i represents

a is an integer of from 7 to 49

b is an integer of from 10 to 98

c is O, or an integer of from 1 to 4

d is O or 1

n is 0 or 1

X¹, X² & X³ individually represent H, a C_{1 to 5} alkyl group or a C_{1 to 5} hydroxyalkyl group

-C-(C_xH_yZ_z)CH₃ ( 3 ) where Z is -OH, -OP_i, -OSO₃ ^Θor an epoxy oxygen

x is an integer of from 12 to 20

y is an integer of from 20 to 40

z is 0, or an integer of from 1 to 4; provided that at least one out of R² & R³ is either a phosphate residue or a sulphate residue.

2. A compound according to claim 1 wherein R¹ contains 1 to 33 carbon atoms and R⁵ contains 1 to 28 carbon atoms.

3. A compound according to claim 2 wherein R¹ contains 8 to 33 carbon atoms, R⁴ contains 8 to 49 carbon atoms and

R⁵ contains 8 to 28 carbon atoms.

4. A compound according to claim 1, claim 2 or claim 3 wherein R⁴ is phosphorylated or sulphated.

5. A compound according to any one of claims 1 to 4 wherein neither R² nor R³ represents H.

6. A process for synthesising a modified pseudoceramide according to any one of claims 1 to 5 which comprises the step of phosphorylation and/or sulphation of

pseudoceramide having the structure (1):

(1)

where R represents the group: O

R⁴-C- , or the group

R⁵-O-CH₂CH CH₂- ;

OR² R¹ represents a linear or branched, saturated or urisaturated, hydroxylated or

non-hydroxylated, phosphorylated or

non-phosphorylated, sulphated or

non-sulphated aliphatic hydrocarbon having from 1 to 49 carbon atoms;

A represents H or the group:

(2)

R² & R³ individually represent H or a sugar

residue provided that at least one of

R² and R³ is H; R⁴ represents a linear or branched,

saturated or unsaturated, hydroxylated or non-hydroxylated,

norr-phosphorylated,

non-sulphated aliphatic hydrocarbon group having from 1 to 49 carbon atoms or the group Y-O-(C_aH_b)- ; R⁵ represents a linear or branched,

saturated or unsaturated, hydroxylated or non-hyroxylated,

non-phosphorylated, non- sulphated aliphatic hydrocarbon group having from 1 to 49 carbon atoms; and P_i, a, b, c, d, n, X¹, X², X³ and Y are as defined in claim 1.

7. A composition suitable for topical application to skin, hair or nails, which comprises: i. an amount of from 0.0001 to 20% by weight of the

modified pseudoceramide according to any one of claims 1 to 5 and ii. a cosmetically acceptable vehicle for the modified pseudoceramide.

8. The use of at least 0.0001% by weight of a modified pseudoceramide according to any one of claims 1 to 5 as an agent for skin water barrier repair, in a topical

composition comprising a major proportion of a cosmetically acceptable vehicle for the modified pseudoceramide.

9. The use of at least 0.0001% by weight of a modified pseudoceramide according to any one of claims 1 to 5 as an agent for improving nails or as an agent for improving hair.

10. A method for the treatment of skin, hair or nails which comprises topical application thereto of a

composition according to claim 7.