FR3076211A1 - USE OF CYCLOALKYL DERIVATIVES (HERERO) AS DEODORANT AGENTS - Google Patents

Abstract

The present invention relates to the use of at least one compound of the following formula (I) in which X denotes an oxygen atom, a -CH (OR) - radical or a -CH2- radical; R1 is a cycloalkyl radical, a C1-C6 alkyl radical or an -OR radical; R2 a -COOH radical or an -SO3H radical; R3 an OR radical, an O-monosaccharide radical, or an O-oligosaccharide radical; R4 an NHR radical, or an OR radical; as well as its salts, its solvates and its optical and / or geometric isomers, including enantiomers and diastereomers, its racemates, alone or as a mixture, for the treatment of bad body odors, in particular linked to perspiration, and in particular bad axillary odors . The present invention also relates to a topical deodorant and / or antiperspirant composition, comprising as deodorant active agent at least one compound of formula (I) as defined above and at least one additional deodorant active agent different from the compounds of formula (I ) and / or at least one antiperspirant active.

Description

The present invention also relates to a method for treating body odors, in particular axillary odors using at least one (herero) cycloalkyl derivative.

The present invention further relates to a cosmetic composition containing at least one (herero) cycloalkyl derivative and an antiperspirant agent and / or an additional deodorant active agent, as well as the use of such compounds for the treatment of body odors, in particular of axillary odors.

In the cosmetic field, it is well known to use in topical application, deodorant products containing active substances of deodorant type and / or of antiperspirant type to reduce or even eliminate body odors. These body odors, especially axillary, are generally unpleasant.

Deodorant active agents therefore have the function of reducing or preventing the formation of these unpleasant odors.

In addition, antiperspirant substances have the effect of limiting the flow of sweat, and generally consist of aluminum salts.

Deodorant substances generally destroy the resident bacterial flora. Among these substances, the most used are Triclosan (2,4,4'-trichloro-2'hydroxydipényléther) and farnesol which have the drawback of significantly modifying the ecology of the skin flora. There are also substances that decrease the growth of bacteria. Among these substances, mention may be made of transition metal chelators such as EDTA or DPTA. These materials deprive the environment of the metals necessary for the growth of bacteria.

The destruction of the resident bacterial flora can favor the multiplication of opportunistic bacteria capable of generating an infection, a fortiori on depilated areas such as the armpits. On the other hand, certain bacteria present in the natural flora of the skin such as Staphylococcus epidermidis are known to have a beneficial effect on the skin by participating in particular in their regeneration (Seminars in

Immunology 2013, 25, 370-377, Sci. Transl. Med. 2017, 9, 1-11).

There is therefore a need to identify new deodorant active agents which can be incorporated into a topical cosmetic formulation making it possible to treat bad body odors, in particular linked to human perspiration, and in particular axillary odors, but which are moreover likely to do not completely eradicate the cutaneous bacterial microflora, in particular the axillary bacterial microflora.

The object of the present invention is in particular to meet these needs.

In particular, the aim of the present invention is to provide derivatives making it possible to treat bad body odors linked to human perspiration, such as axillary odors.

One of the aims of the present invention is also to provide derivatives having deodorant activity, for reducing odors, in particular in humans, and more particularly for combating body odors, such as axillary odors in particular in the form of compositions, in particular topical.

(Herero) cycloalkyl derivatives such as derivatives of sialic acid and / or quinic acid are known, as in WO 2009/155665 for preventing and treating infections of a subject by a pathogen and, as in WO 00 06115 , to regulate inflammatory responses, treat disorders and conditions related to it and / or improve the appearance of the skin. In the cosmetic field, and in particular in EP 3,067,040, sialic acid derivatives are proposed for the purposes of prevention and / or treatment of aging processes, and in particular of aging of the skin. In combination with anti-inflammatory active agents, adhesion-inhibiting active agents, sebum-reducing active agents and a sclerolide compound, sialic acid derivatives are described in US 2003/0072777 in anti-acne compositions.

On the other hand, to the knowledge of the inventors, it has never been proposed to use (herero) cycloalkyl derivatives such as sialic acid and / or quinic acid derivatives for the purpose of acting against odors body.

The inventors have surprisingly discovered that compounds of formula (I) detailed below, alone or as a mixture, have good deodorant efficacy and can be easily formulated in a product intended to reduce body odors, and in particular axillary odors, alone or possibly in combination with antiperspirants and / or conventional additional deodorant active agents, different from the compounds of the invention, without the drawbacks mentioned above.

The compounds of formula (I) according to the invention advantageously have a deodorant activity, making it possible to treat bad body odors linked to human perspiration, such as axillary odors.

The subject of the present invention is the use of at least one compound of formula (I) as defined below as well as its salts, its solvates and its optical and / or geometric isomers, including enantiomers and diastereoisomers, its racemates , alone or as a mixture, for the treatment of bad body odors, in particular linked to perspiration, and in particular bad axillary odors.

The present invention also relates to the use of at least one compound of formula (I) as defined below as well as its salts, its solvates and its optical and / or geometric isomers, including enantiomers and diastereoisomers, its racemic, alone or in mixture, as a deodorant agent for treating body odors, preferably axillary odors.

The subject of the invention is also a method of cosmetic and non-therapeutic treatment of keratin materials to combat body odors, characterized in that it comprises at least one step of topical application of at least one compound of formula (I ) as defined below as well as its salts, its solvates and its optical and / or geometric isomers, including enantiomers and diastereoisomers, its racemates, alone or as a mixture or of a composition containing it, in particular under the armpits .

The subject of the invention is also a topical composition, preferably cosmetic, in particular deodorant and, if necessary antiperspirant, comprising as deodorant active agent at least one compound of formula (I) as defined below as follows that its salts, its solvates and its optical and / or geometric isomers, including enantiomers and diastereoisomers, its racemates, alone or in mixture, and at least one additional deodorant active different from the compounds of formula (I) and / or at least one antiperspirant active.

Against all expectations, the inventors have discovered that (herero) cycloalkyls such as derivatives of sialic acid and / or quinic acid, and in particular the compounds of formula (I) according to the invention have good efficacy against bad body odors, and in particular against axillary odors. Indeed, and as has been demonstrated in the examples below, the compounds of formula (I) according to the invention make it possible to reduce the power and the intensity of the odor caused by sweat.

On the other hand, the inventors have found, unexpectedly, that these compounds make it possible to preserve the cutaneous bacterial microflora of the keratin materials to which they are applied, in particular the axillary bacterial microflora.

What is more, taking into account their specificity of natural products, the (herero) cycloalkyl derivatives of formula (I) such as derivatives of sialic acid and / or quinic acid are, in contrast to conventional deodorant active agents, in agreement with consumer expectations.

In addition, as is apparent from the examples below, the compounds of formula (I) prove to be compatible with other additional deodorant active agents and / or conventional antiperspirant active agents and their respective efficiencies are not altered. What is more, the presence of the compounds according to the invention in combination with these conventional active agents makes it at least as effective.

FORMULA COMPOUNDS (1)

The invention therefore describes at least one compound of formula (I) as deodorant active in the form of a composition, preferably topical, as well as the use of such a compound of formula (I) for the treatment bad body odors, in particular linked to perspiration, and in particular axillary odors, alone or in combination with an additional deodorant compound different from the compound of formula (I) and / or an antiperspirant active.

Said compounds correspond to the following formula (I):

in which

- X denotes an oxygen atom, a radical -CH (OR) - or a radical -CH2-;

- Ri denotes

a C5-C6 cycloalkyl radical substituted with at least one OR radical,

- a C1-C6 alkyl radical, substituted by at least one OR radical, or

- a radical -OR;

- R2 denotes a radical -COOH or a radical -SO3H;

- R3 denotes

- an OR radical,

- an optionally substituted O-monosaccharide radical, or

- an optionally substituted O-oligosaccharide radical, preferably an O-oligosaccharide comprising between 2 and 5 monosaccharides, more preferably an O-disaccharide radical;

- R4 denotes an NHR ’radical or an OR radical;

- R denotes a hydrogen atom or a protecting group for a hydroxyl function, in particular an acetyl or benzyl radical;

- R ′ denotes a hydrogen atom or a protective group of primary amine function, in particular an acetyl radical;

as well as their salts, their solvates and their optical and / or geometric isomers, including enantiomers and diastereoisomers, their racemates, alone or as a mixture.

According to a particular embodiment of the invention, the compound of formula (I) is in the following stereochemical configuration:

For the purposes of the present invention, unless a different indication is given, a “salt” denotes an addition salt with an organic or inorganic base cosmetically acceptable such as the hydroxides of alkali metal, alkaline earth metal as soda, potash, ammonia, amines or alkanolamines; as inorganic salts, there may be mentioned the sodium or potassium salts as well as the zinc (Zn ²⁺ ), calcium (Ca ²⁺ ), copper (Cu ²⁺ ), iron (Fe ²⁺ ) salts, strontium (Sr ²⁺ ), magnesium (Mg ²⁺ ), manganese (Mn ²⁺ ); as organic salts, there may be mentioned the ammoniums of formula NH_T or the ammoniums of formula Υ3ΝΙ-Γ, NY3 denoting an organic amine, the radicals Y being identical or different, two or three radicals Y being able to form a ring in pairs with the nitrogen atom which carries them or NY3 which can designate an aromatic amine. The organic amines are, for example, alkylamines, such as for example methylamine, dimethylamine, trimethylamine, triethylamine or ethylamine, or hydroxyalkylamines, such as, for example, 2-hydroxyethylamine, bis- (2-hydroxyethyl) amine or tri- (2-hydroxyethyl) amine, or cycloalkylamines, such as for example bicyclohexylamine or glucamine, piperidine, or pyridines and the like, for example collidine, quinine or quinoline, or basic amino acids , such as lysine or arginine.

The salts of the compounds of formula (I) according to the invention can be advantageously chosen from the metal salts Cu ²⁺ , Mn ²⁺ and Zn ²⁺ , the alkaline salts Li ⁺ , Na ⁺ and K ⁺ and the alkaline earth salts Ca ²⁺ and Mg ² +, preferably alkaline salts such as Na ⁺ .

According to another variant, the organic salts of the compounds of formula (I) according to the invention can be advantageously chosen from ammoniums, preferably from salts of basic amino acids such as for example lysine or arginine or from diethanolamine or triethanolamine salts.

In the case where the compounds according to the invention are in the form of a salt, the cations are of course present in an amount ensuring the electroneutrality of the compounds of formula (I) ·

For the purposes of the present invention, unless a different indication is given, an “oligosaccharide” designates a polyosidic sugar which is a polymer made up of several oses, typically from 2 to 10, even from 2 to 5, possibly amines linked to each other by O-osidic bonds, said polymers being composed of monosaccharide units optionally aminated, said monosaccharide units comprising at least 5 carbon atoms, preferably 6, particularly the mono-osidic units are linked together in 1.4 or 1.6 as an a (alpha) or β (beta) anomer, each osidic unit possibly being of L or D configuration, preferably L, which can be in the form of salts and / or solvates such as hydrates.

They are more particularly polymers formed from a certain number of oses (or monosaccharides) having the general formula: - [C _x (H2O) _y )] n- with x being an integer greater than or equal to 5, of preferably x is greater than or equal to 6, in particular x is inclusive between 5 and 7, preferably x = 6, and y is an integer which represents x - 1, and n is an integer greater than or equal to 2, particularly inclusive between 2 and 5, more particularly n = 2 and more preferably “oligosaccharide radical” denotes a lactose radical.

For the purposes of the present invention, unless a different indication is given, an “optionally substituted O-monosaccharide radical” or “optionally substituted O-oligosaccharide” denotes a monosaccharide or an oligosaccharide optionally substituted by one or more group (s) ) amino NRaRb or by one or more -O- (CH2) _m -NRaRb groups, ie at least one of the hydroxy groups of at least one sugar unit is replaced by an -O- (CH2) m-NRaRb or NRaRb group, with m denoting an integer inclusive between 1 and 8 such as 6 and Ra and Rb, identical or different, representing i) a hydrogen atom, ii) a (Ci-C6) alkyl group optionally substituted, preferably by a or more hydroxy or NH2 groups, iii) an aryl group such as phenyl, iv) an aryl (Ci-C4) alkyl group such as benzyl, v) a radical -C (Y) - (Y ') _P -R'a with Y and Y ', identical or different, representing an oxygen, sulfur or -N (R'2) - atom, preferably nce oxygen, p = 0 or 1, preferably 0; and R'a and R'b representing i) to iv) of Ra and Rb defined above, and in particular R'a denoting a (Ci-C6) alkyl group such as methyl. In other words, when the O-monosaccharide radical or the O-oligosaccharide radical is substituted by one or more amino group (s) NRaRb at least one osidic unit is deoxylated at at least one position of said unit.

Preferably Ra and Rb represent a hydrogen atom, or a (Ci-C4) alkylcarbonyl group, in particular acetyl.

Even more preferably, an O-monosaccharide or O-oligosaccharide radical may be substituted by one or more, in particular 1, 2 or 3 amino group (s) NRaRb, in which Ra and Rb represent a hydrogen atom, or a (Ci-C4) alkylcarbonyl group, in particular an acetyl or also 1, 2 or 3 group (s) -O- (CH2) _m NRaRb, in which Ra and Rb are hydrogen atoms and m denotes an integer between 4 and 8, in particular between 5 and 7 and even more particularly equal to 6.

Preferably, the 0-mono or O-oligosaccharide radical is linked to the rest of the molecule by a bond between the carbon atom Ci of one of the sugars of said mono or oligosaccharide radical, this bond being able to be anomeric a or β.

The term “protective group for the hydroxy function” is known to a person skilled in the art, especially in the two works “Protective Groups in Organic Synthesis”, TW Greene, John Willey & Sons ed., NY, 1981, pp. 193-217; "Protecting Groups", P. Kocienski, Thieme, 3 ^rd ed., 2005.

In particular, the group protecting the hydroxy function according to the invention is chosen from:

- (Ci-C6) alkyl (thio) carbonyl such as formyl, acetyl or t-butylcarbonyl, preferably acetyl;

- (di) aryl (Ci-C4) alkyl or triaryl (Ci-C4) optionally substituted alkyl such as 9-anthracenyl-methyl, phenylmethyl (benzyl), diphenylmethyl or triphenylmethyl optionally substituted by one or more groups chosen in particular from halogen, ( C1-C4) alkyl, (C1-C4) alkoxy such as methoxy, hydroxy, (C1-C4) alkylcarbonyl, (di) (C1-C4) (alkyl) amino such as dimethylamino; preferably benzyl;

- optionally substituted arylsulfonyl such as p-toluenesulfonyl (Tos);

- ReRfRgSi- with R _e , Rf, and R _g , identical or different, representing a (Ci-C6) alkyl group, optionally substituted aryl, (di) aryl (Ci-C4) optionally substituted alkyl, triaryl (Ci-C4) optionally substituted alkyl, such as benzyl, in particular chosen from trimethyl silyl or TMS, triethylsilyl, isopropyldimethylsilyl, terbutyldimethylsilyl or TBDMS, (triphenylmethyl) dimethylsilyl, t-butyldiphenylsilyl, methyldiisopropylsilyl, methyl-silyl, diethyltyl) p-xylylsilyl, triisopropyl silyl, triphenyl silyl;

- or then two contiguous hydroxy groups can be protected by an alkylene group * -C (R ¹ ) (R ^m ) - (C (R ^k ) (R ⁱ )) q- * as drawn below:

with R ¹ , R ^k , R ¹ , and R ^m , identical or different, representing a hydrogen atom or a (Ci-C4) alkyl, (poly) halo (Ci-C4) alkyl, optionally substituted aryl group such as phenyl, aryl (Ci-C4) alkyl such as benzyl, (poly) halo (Ci-C4) alkoxy, (Ci-C4) alkoxy, halogen, (di) (Ci-C4) (alkyl) amino, hydroxy, or so two groups R ¹ and R ^k and / or R ¹ , and R ^m form together with the carbon atom which carry them an oxo group or a (hetero) clycloalkyl such as cyclohexyl or cyclopropyl; q is 0, 1, 2 or 3, preferably * -C (R ¹ ) (R ^m ) - (C (R ^k ) (R ⁱ )) q- * represents a methylene, ethylene, propylene, dimethylmethylene, * - C (CH3) 2- * or diphenylmethylene * -C (Ph) 2- *, cyclopentylidene, cyclohexylidene, cycloheptylidene, benzylidene, p-methoxybenzylidene,

2,4-dimethoxybenzylidene, methoxymethylene and ethoxymethylene.

More particularly, the protecting group for the hydroxy function is chosen from acetyl or benzyl, more particularly acetyl.

Within the meaning of the present invention, and unless a different indication is given:

"Alkyl" denotes a linear or branched radical containing from 1 to 6 carbon atoms, in particular from 1 to 4 carbon atoms, for example methyl, ethyl, n-propyl, iso-propyl, butyl, n-pentyl, n -hexyl;

"(Cx-Cy) alkyl" denotes an alkyl radical as defined above, said alkyl radical comprising x to y carbon atoms;

“Cycloalkyl” denotes a monocyclic hydrocarbon group, preferably monocyclic saturated or containing one or more non-aromatic ethylenic unsaturations, comprising 5 or 6 members, this cycloalkyl possibly being substituted by one or more radicals, identical or different chosen from alkyl, hydroxyalkyl radicals , and alkoxy. Preferably, according to the present invention, the cycloalkyl is saturated and comprises from 5 to 8 members, in particular 5 or 6, and more preferably is chosen from cyclopentyl and cyclohexyl;

the expression "at least one" is equivalent to "one or more" and may in particular denote from 1 to 8, in particular 1 to 6; in particular from 1 to 5, or even from 1 to 3;

the expression "inclusive" for a range of concentrations means that the limits of the range are part of the defined interval;

"Isomer" means optical isomers, geometric isomers as well as tautomers of the compounds of formula (I); and “solvated” designates the different forms that a compound of formula (I) can take depending on the solvent in which it is found by interacting with the molecules of this solvent to form interactions of ion-dipole type, hydrogen bonds or van der Waals bonds; the acceptable solvates of the compounds used in the present invention include conventional solvates such as those formed during the last stage of preparation of said compounds due to the presence of solvents; by way of example, mention may be made of solvates due to the presence of water (hydrates) or of linear or branched alcohols such as ethanol or isopropanol.

It is understood that for the compounds of formula (I) as defined above when R3 represents an O-monosaccharide radical, then the monosaccharide can be in pyranose form (the sugar heterocycle which constitutes it is 6-membered) or furanose ( the sugar heterocycle which constitutes it is 5-membered).

When R3 represents an O-oligosaccharide radical, the oligosaccharide preferably comprises the chain of 2 to 5 identical or different saccharide units which may be in furanose or pyranose form.

In the context of the present invention, the oligosaccharide may be a disaccharide which results from the chain of a saccharide unit in furanose form and of a unit in pyranose form or the chain of a saccharide unit in pyranose form and of a unit in furanose form or else of a chain of two saccharide units in pyranose form, such as lactose, N-acetyllactosamine or 1-O-aminohexyllactose.

In the context of the present invention, the monosaccharide can be a galactose or a glucosamine.

Whether it is a monosaccharide or oligosaccharide radical, each saccharide unit can be in the levorotatory or D dextrorotatory form, and in the anomeric form a or β.

In the context of the invention, and unless otherwise stated, "skin" means human skin, for example the skin of the face, of the body, in particular the skin of the hands, feet, armpits, scalp.

In the context of the invention, by “body odors” is meant, for example, axillary odors, plantar odors.

According to one embodiment, the compounds of formula (I) are such that R denotes a hydrogen atom and R2 denotes a carboxy radical -COOH.

According to a particular embodiment, the compounds of formula (I) are such that X denotes an oxygen atom, R denotes a hydrogen atom, R2 denotes a carboxy radical -COOH and R4 denotes an NHR 'radical, with R 'as previously defined in particular NHCOCH3.

According to a particular embodiment, the compounds of formula (I) are such that X denotes a methylene radical -CH2-, R denotes a hydrogen atom, R2 denotes a radical -COOH, R4 denotes a hydroxy radical.

According to a particular embodiment, Ri denotes a C1-C6 alkyl radical, comprising at least one OR substituent with R as defined above, preferably a C1-C4 alkyl radical such as propyl, said alkyl radical being substituted with at least one hydroxy radical, in particular Ri denotes a radical of formula - (CHOH) _n -CH2-OH with n = 1,2,3 or 4 and preferably n = 3;

According to a particular embodiment, Ri denotes a radical -OR with R as defined above and preferably such that R denotes a hydrogen atom.

According to a particular embodiment, R3 denotes a radical -OR with R as defined above and preferably such that R denotes a hydrogen atom.

According to a particular embodiment, R3 denotes an O-monosaccharide radical as defined above, in particular an O-galactose radical.

According to a particular embodiment, R3 denotes an O-oligosaccharide radical, preferably an O-disaccharide radical as defined above, in particular an O-lactose radical optionally substituted by one or more amino group (s) NRaRb or by one or several groups -O- (CH2) _m -NRaRb, that is to say that at least one of the hydroxy groups of at least one osidic unit is replaced by a group -O- (CH2) _m -NRaRb or NRaRb , with m denoting an integer inclusive between 1 and 8 such as 6 and Ra and Rb, identical or different, representing i) a hydrogen atom or v) a COR'a radical in which R'a represents a group ( Ci-C6) alkyl such as methyl. Still according to this embodiment, R3 can thus denote lactose, N-acetyllactosamine or 1-O-aminohexyllactose.

According to a particular embodiment, R4 denotes an NHR radical "with R" denotes a hydrogen atom or an acetyl radical, in particular an acetyl radical.

According to a preferred variant of the invention, the compounds of formula (I) are such that

X denotes a methylene radical -CH2-, R2 denotes a radical -COOH, R3, Ri and R4 denote OH and R denotes a hydrogen atom.

According to another variant of the invention, the compounds of formula (I) are such that X 5 denotes an oxygen atom, R denotes a hydrogen atom, R2 denotes a radical -COOH, R4 denotes an NHR 'radical with R 'as defined above in particular acetyl, and Ri denotes a C1-C6 alkyl radical comprising at least one hydroxy radical such as a radical of formula - (CHOH) n-CH2-0H with n = 1,2,3 or 4 and preferably n = 3.

According to a preferred embodiment of the invention, R3 denotes a disaccharide radical, preferably lactose (D-galactopyranosyl-3 (1—> 4) D-glucopyranose) linked in a- (2—> 3) to the rest of the compound, optionally substituted such as N-acetylactosamine or hearing 1-O-aminohexyllactose.

Mention may be made, as examples of compounds of formula (I) according to the invention, of the following compounds (a) to (e) as well as their salts, in particular their alkaline salts such as their sodium salt, their solvates and their optical isomers, including enantiomers and

H v \ * H 0 0 s oh vs H 0 0 h 0 h (B) Quinic acid HO f 'ύ .OH HO ' s OH HO O a! vs z O COONa Sodium salt of 3'-Sialylgalactose H HKT \ ..'OH OH (vs) O HN O OH HO OH Ά ^ OH O z ° Sodium salt of 3'-a-Sialyl-N-acetyllactosamine HO ^ OH HO. p o 7 AJ \ / ° COONa H 1 HO ^ _? OH OH (D)

According to a particular embodiment of the invention, the compound of formula (I) is chosen from 3'-O-sialyllactose, 3'-sialylgalactose, 3'-a-sialyl-Nacetyllactosamine and 1-0- aminohexyl 3'-sialyllactose as well as their salts, in particular their alkaline salts such as their sodium salt, their solvates and their optical isomers, including enantiomers and diastereoisomers, their racemics, alone or as a mixture.

According to a particularly preferred embodiment of the invention, the compound of formula (I) is 3′-O-sialyllactose as well as its salts, in particular its alkaline salts such as its sodium salt of formula (a), and its solvates:

A compound according to the invention can be used in a cosmetic composition.

Such a cosmetic composition may comprise a content of compound of formula (I) as defined above, varying from 0.1% to 20% by weight, better varying from 0.2% to 15% by weight, better still varying from 0 , 5% to 10% by weight, relative to the total weight of the composition.

Deodorant and / or antiperspirant active ingredients

A composition according to the invention also comprises an additional deodorant active agent different from a compound of formula (I) and / or an antiperspirant active agent.

In particular, a composition according to the invention comprises a content of additional deodorant active agent and / or antiperspirant active agent which can vary from 0.001% to 30% by weight, preferably which can vary from 0.01% to 20% by weight, better can vary from 0.02% to 15% by weight relative to the total weight of the composition.

Thus, according to an alternative embodiment, the composition according to the invention contains one or more additional deodorant active agents, different from the compounds of formula (I) according to the invention.

The term "deodorant active" means any substance capable of masking, absorbing, improving and / or reducing the unpleasant odor resulting from the breakdown of human sweat by bacteria.

These additional deodorant active agents can be chosen, for example, from:

- water-soluble zinc salts, such as for example zinc pyrrolidone carboxylate (more commonly called zinc pidolate), zinc sulphate, zinc chloride, zinc lactate, zinc gluconate and zinc phenolsulfonate;

- bacteriostatic agents or bactericidal agents such as 2,4,4'-trichloro-2'hydroxydiphényléther (Triclosan), 2,4-dichloro-2'-hydroxydiphenyléther, le 3 ', 4', 5'trichlorosalicylanilide, 1- (3 ', 4'-dichlorophenyl) -3- (4'-chlorophenyl) urea (Triclocarban) or 3,7, 11-trimethyldodeca-2,5,10-trienol (Farnesol);

- quaternary ammonium salts such as cetyltrimethylammonium salts, cetylpyridinium salts;

- chlorhexidine and salts;

- diglycerol monocaprate, diglycerol monolaurate, glycerol monolaurate; and

- polyhexamethylene biguanide salts.

Generally, these additional deodorant active agents are advantageously present in an amount less than that considered when they are formulated as the sole deodorant active agent in a deodorant composition. This reduction can range from 1.0% to 20.0%.

A composition according to the invention can comprise a content of additional deodorant active agents which can vary from 0.01% to 50.0% by weight, and preferably a content which can vary from 0.1% to 30.0% by weight per relative to the total composition weight.

According to another alternative embodiment, a composition according to the invention contains at least one or more antiperspirant active agents.

The term "antiperspirant active" means a compound which, by itself, has the effect of decreasing the sweat flow, decreasing the sensation on the skin of humidity linked to human sweat or masking human sweat.

These antiperspirant active agents are preferably chosen from aluminum and / or zirconium salts; zirconium hydroxychloride and aluminum hydroxychloride complexes with an amino acid such as those described in patent US Pat. No. 3,792,068 commonly known under the name "ZAG complexes". Such complexes are generally known by the name ZAG (when the amino acid is Glycine). ZAG complexes usually have an Al / Zr quotient ranging from about 1.67 to 12.5 and a Metal / Cl quotient ranging from about 0.73 to 1.93. Among these products, mention may be made of aluminum zirconium octachlorohydrex GLY, aluminum zirconium pentachlorohydrex GLY, aluminum zirconium tetrachlorohydrate GLY and aluminum zirconium trichlorohydrateGLY.

Among the aluminum salts, there may be mentioned aluminum hydrochloride, aluminum chlorohydrex, aluminum chlorohydrex PEG, aluminum chlorohydrex PG, aluminum dichlorohydrate, aluminum dichlorohydrex PEG, aluminum dichlorohydrex PG, aluminum sesquichlorohydrate, aluminum sesquichlorohydrex PEG, aluminum sesquichlorohydrex PG, alum salts, aluminum sulfate, aluminum zirconium octachlorohydrate, aluminum zirconium pentachlorohydrate, aluminum zirconium tetrachlorohydrate, aluminum zirconium trichlorohydrate and more particularly the aluminum hydroxychloride marketed by the company REHEIS under the name REACH 301 or by the company GUILINI CHEMIE under the name ALOXICOLL PF 40. Aluminum and zirconium salts are for example that sold by the company REHEIS under the name REACH AZP-908-SUF.

According to a preferred embodiment of the invention, the composition comprises at least one antiperspirant active, and in particular chosen from aluminum and / or zirconium salts. In particular, the antiperspirant active agents according to the invention can be chosen from aluminum choloride hexahydrate, aluminum hydrochloride and their mixtures.

A composition according to the invention can comprise a content of antiperspirant active agents which can vary from 0.001% to 50% by weight, preferably which can vary from 0.1% to 30% by weight, better still which can vary from 0.1% to 20, 0% by weight relative to the total weight of the composition.

According to a particular embodiment of the invention, the mass ratio of compound (s) of formula (I) / additional deodorant active (s) and / or antiperspirant active (s) varies of

0.001 to 10, better varies from 0.01 to 5.0, better still varies from 0.02 to 1.0.

Compositions

The composition according to the invention can be in all the galenical forms conventionally used for topical application and in particular in the form of aqueous gels, aqueous or hydroalcoholic solutions. They can also, by adding a fatty or oily phase, be in the form of dispersions of the lotion type, emulsions of liquid or semi-liquid consistency of the milk type, obtained by dispersion of a fatty phase in an aqueous phase. (O / W) or vice versa (W / O), or of suspensions or emulsions of soft, semi-solid or solid consistency of the cream or gel type, or also of multiple emulsions (W / O / W or O / W / H), microemulsions, vesicular dispersions of the ionic and / or nonionic type, or wax / aqueous phase dispersions.

The composition according to the invention is formulated in a physiologically acceptable medium. By "physiologically acceptable medium" is meant a medium compatible with human keratin materials, in this case the skin. The physiologically acceptable medium is preferably a cosmetically or dermatologically acceptable medium, that is to say without odor, color or unpleasant appearance, and which does not generate discomfort, or tightness unacceptable to the user.

These compositions are prepared according to the usual methods known to those skilled in the art.

A composition according to the invention can comprise at least one aqueous phase, as it can be anhydrous.

In the context of the invention, by “anhydrous composition”, is meant a composition containing less than 2.0% by mass of water, or even less than 0.5% of water, and in particular free of water, water not being added during the preparation of the composition but corresponding to the residual water provided by the mixed ingredients.

According to another particular form of the invention, the compositions according to the invention can be solid, in particular in the form of a stick or stick.

In the context of the invention, by “solid composition”, it is meant that the measurement of the maximum force measured in texturometry during the insertion of a probe into the sample of formula must be at least equal to 0.25 Newton, in particular at least equal to 0.30 Newton, in particular at least equal to 0.35 Newton, appreciated under precise measurement conditions as follows.

The formulas are poured hot into pots 4 cm in diameter and 3 cm deep. Cooling is done at room temperature. The hardness of the formulas produced is measured after 24 hours of waiting. The pots containing the samples are characterized in texturometry using a texturometer such as that marketed by the company Rhéo TA-XT2, according to the following protocol: a 5 mm diameter stainless steel ball probe is brought into contact with the sample at a speed of 1 mm / s. The measurement system detects the interface with the sample with a detection threshold of 0.005 newtons. The probe sinks 0.3 mm into the sample, at a speed of 0.1 mm / s. The measuring device records the evolution of the force measured in compression over time, during the penetration phase. The hardness of the sample corresponds to the average of the maximum values of the force detected during penetration, on at least 3 measurements.

Aqueous phase

According to another advantageous variant, the composition comprises at least one aqueous phase. The content of aqueous phase in the composition can be between 0% and 98.0% by weight relative to the total weight of the composition.

The compositions according to the invention can comprise at least one aqueous phase.

They are in particular formulated in aqueous lotions or in water-in-oil emulsion, oil-in-water, or in multiple emulsion (triple oil-in-water-in-oil emulsion or in oil-in-water emudans (such emulsions are known and described for example by C. FOX in "Cosmetics and Toiletries" - November 1986 - Vol 101 - pages 101-112).

The aqueous phase of said compositions can contain water and in general other solvents soluble or miscible in water. Solvents or water-miscible solvents may include short chain mono alcohols, for example C1-C4 such as ethanol, isopropanol; diols or polyols such as ethylene glycol,

1,2-propylene glycol, 1,3-butylene glycol, hexylene glycol, diethylene glycol, dipropylene glycol, 2-ethoxyethanol, diethylene glycol monomethyl ether, triethylene glycol monomethyl ether and sorbitol. Use will more particularly be made of propylene glycol and glycerin, propane 1,3 diol.

When the composition is in the form of an emulsion, it generally contains, depending on the nature of the emulsion, one or more emulsifying surfactants.

The total amount of emulsifiers will preferably be in active ingredient contents ranging from 1% to 8% by mass and more particularly from 2% to 6% by mass relative to the total mass of the composition.

Fat phase

The compositions according to the invention may contain at least one organic liquid phase immiscible in water called the fatty phase. This generally comprises one or more hydrophobic compounds which make said phase immiscible in water. Said phase is liquid (in the absence of structuring agent) at room temperature (20-25 ° C). Preferably, the water-immiscible organic liquid phase according to the invention generally comprises at least one volatile oil and / or a non-volatile oil and optionally at least one structuring agent.

By "oil" is meant a fatty substance which is liquid at room temperature (25 ° C) and atmospheric pressure (760mm of Hg, ie 1.05 × 10 ⁵ Pa). The oil can be volatile or non-volatile.

By "volatile oil" is meant within the meaning of the invention an oil capable of evaporating on contact with the skin in less than an hour, at room temperature and atmospheric pressure.

The volatile oils of the invention are volatile cosmetic oils, liquid at room temperature, having a non-zero vapor pressure, at room temperature and atmospheric pressure, ranging in particular from 0.13 Pa to 40,000 Pa (10 ' ³ to 300 mm from

Hg), in particular ranging from 1.3 Pa to 13,000 Pa (0.01 to 100 mm Hg), and more particularly ranging from 1.3 Pa to 1300 Pa (0.01 to 10 mm Hg).

By “non-volatile oil” is meant an oil which remains on the skin at room temperature and atmospheric pressure for at least several hours and in particular having a vapor pressure of less than 10 ' ³ mm Hg (0.13 Pa).

The oil can be chosen from all physiologically acceptable and in particular cosmetically acceptable oils, in particular mineral, animal, vegetable and synthetic oils; in particular volatile or non-volatile hydrocarbon and / or silicone and / or fluorinated oils and their mixtures.

More specifically, by "hydrocarbon oil" is meant an oil comprising mainly carbon and hydrogen atoms and optionally one or more functions chosen from hydroxyl, ester, ether and carboxylic functions. Generally, the oil has a viscosity of 0.5 to 100,000 mPa.s, preferably from 50 to 50,000 mPa.s and more preferably from 100 to 300,000 mPa.s.

As an example of a volatile oil which can be used in the invention, there may be mentioned:

volatile hydrocarbon oils chosen from hydrocarbon oils having from 8 to 16 carbon atoms, and in particular Cs-C16 isoalkanes of petroleum origin (also called isoparaffins) such as isododecane (also called 2,2,4,4, 6pentamethylheptane), isodecane, isohexadecane, and for example the oils sold under the trade names of Isopars or Permyls, branched Cs-C16 esters, iso-hexyl neopentanoate, and mixtures thereof; and volatile silicones, such as, for example, linear or cyclic volatile silicone oils, in particular those having a viscosity <8 centistokes (8 10 ′ ⁶ m ² / s), and in particular having from 2 to 7 silicon atoms, these silicones comprising optionally alkyl or alkoxy groups having from 1 to 10 carbon atoms, and mixtures thereof. As volatile silicone oil which can be used in the invention, there may be mentioned in particular octamethyl cyclotetrasiloxane, decamethyl cyclopentasiloxane, dodecamethyl cyclohexasiloxane, heptamethyl hexyltrisiloxane, heptamethyloctyl trisiloxane, hexamethyl disiloxane, octamethyl trisil tetrasiloxane, dodecamethyl pentasiloxane and mixtures thereof;

By way of example of a non-volatile oil which can be used according to the invention, there may be mentioned:

vegetable hydrocarbon oils such as the liquid triglycerides of fatty acids with 4 to 24 carbon atoms such as the triglycerides of heptanoic or octanoic acids or else the oils of wheat germ, olive, sweet almond oil, palm, rapeseed, cotton, alfalfa, poppy, pumpkin, squash, blackcurrant, sunflower, corn, soy, squash, grape seed, sesame, hazelnut, apricot , macadamia, castor, avocado, triglycerides of caprylic / capric acids such as those sold by the company Stearineries Dubois or those sold under the names Miglyol 810, 812 and 818 by the company Dynamit Nobel, jojoba oil;

linear or branched hydrocarbons, of mineral or synthetic origin such as paraffin oils and their derivatives, petrolatum, polydecenes, polybutenes, hydrogenated polyisobutene such as Parleam, squalane;

synthetic ethers having from 10 to 40 carbon atoms such as dipentylether;

synthetic esters, in particular of fatty acids, such as oils of formula R'COOR ² in which R ¹ represents the remainder of a higher linear or branched fatty acid containing from 1 to 40 carbon atoms and R ² represents a hydrocarbon chain in particular branched containing from 1 to 40 carbon atoms with R ¹ + R ² > 10 such as isononyl isononanoate, isopropyl myristate, isopropyl palmitate, C12 to C15 alcohol benzoate;

- fatty alcohols liquid at room temperature with branched and / or unsaturated carbon chain having from 12 to 26 carbon atoms such as octyl dodecanol;

- silicone oils such as non-volatile, linear (dimethicones) or cyclic (cyclomethicones) polydimethylsiloxanes (PDMS); polydimethylsiloxanes comprising alkyl, alkoxy or phenyl groups, during or at the end of the silicone chain, groups having from 2 to 24 carbon atoms; phenylated silicones such as phenyl trimethicones, phenyl dimethicones, phenyl trimethylsiloxy diphenyl siloxanes, diphenyl dimethicones, diphenyl methyldiphenyl trisiloxanes,

2-phenyl ethyl trimethyl-siloxysilicates, and mixtures thereof.

According to a particular embodiment, the composition according to the invention comprises at least one fatty phase. Thus, the fatty phase content in the composition can be between 0% and 98.0% by weight relative to the total weight of the composition.

The composition according to the invention can also contain one or more additional compounds such as active agents, preservatives, antioxidants, complexing agents, perfumes, coloring matters, natural extracts, lightening agents, vitamins, urea, caffeine, depigmenting agents, beta-hydroxy acids such as salicylic acid and its derivatives, alpha-hydroxy acids such as lactic acid and glycolic acid, emollients and humectants, such as methyl ethoxylated glucosides and ethoxylated acylated methyl glucosides, organic and inorganic shielding agents, or mixtures thereof.

It can also contain a water-dispersible agent such as clays, polymers, pigments, aluminum oxides, silicates, talc, magnesium silicates, titanium dioxide, zinc oxide or their mixtures.

The compositions according to the invention can be packaged in the form of roll-on, sticks, aerosol or spray.

The galenical formula is of course adapted to the chosen packaging method.

In the case of a stick, a solid formulation is preferred. In the case of roll-on, aerosols and sprays, lipophilic formulas are preferred.

For example, the compositions in the form of vaporizable fluid lotions are applied to the skin in the form of fine particles by means of pressurization devices.

Throughout the description, including the claims, the expression "comprising a" should be understood as being synonymous with "comprising at least one", unless otherwise specified.

The expressions "between ... and ..." and "ranging from ... to ..." must be understood including limits, unless otherwise specified.

In the description and examples below, unless otherwise indicated, the percentages are percentages by weight. The percentages are therefore expressed by weight relative to the total weight of the composition. The ingredients are mixed, in the order and under the conditions easily determined by a person skilled in the art.

APPLICATION EXAMPLES

A) Study of anti-odor effects (on incubated sweat)

The deodorant activity of the compounds according to the invention was evaluated in the ex-vivo olfactory evaluation test, on incubated sweat.

The compound used according to the invention is the sodium salt of 3'-O-sialyllactose (CAS: 128596-80-5) which is marketed by CARBOSYNTH under the reference OS04397 or compound of formula (a) as defined above . The latter was evaluated in a fresh sweat pool.

The samples were prepared in 10 ml headspace vials, they were incubated at 35 ° C for 24 h with shaking. A sample of sweat with 1 mg of anhydrous aluminum hydroxychloride (ACH) in 1 ml of sweat (i.e. 0.1% corresponding to O.lg / 100 ml) is incubated to serve as a positive reference (slightly smelly) and a sample of sweat only is incubated to serve as a negative reference (smelly).

The samples after incubation are evaluated olfactively by a panel of 6 people blinded on the headspace bottles. The incubated sweat samples containing ACH and sweat alone are evaluated at the same time to serve as negative and positive references, respectively.

Two parameters are evaluated:

- Reduction in the intensity of sweat odor (% compared to the sweat only control),

- The overall power of the odor with 0 for not very powerful and 10 for very powerful.

Table III below provides the results of the evaluations carried out by a panel of

6 persons. The values in the table correspond to the average of the values obtained for the 6 panelists.

Table III:

Sample Power Score Reduction in the intensity of the odor (%) Incubated sweat 9 / Sodium salt of 3’-O-sialyllactose 0.5% 8 11

Conclusion

It is thus noted a general reduction in the odor, both in intensity and in the power of the odor, with the sodium salt of 3’-O-sialyllactose compared to the negative reference, sweat incubated alone.

B) Formulations

The following formulations were prepared according to the invention:

Aqueous formulation 1:

ingredients % by mass relative to the total mass of the composition Crosslinked poly (acrylic acid) (Carbomer) 0.3

conservatives 1.0 Sodium salt of 3’-O-sialyllactose 0.5 Water Qsp 100

Formulation 1 produces a deodorant effect.

Aqueous formulation 2:

ingredients % by mass relative to the total mass of the composition Crosslinked poly (acrylic acid) (Carbomer) 0.3 conservatives 1.0 Sodium salt of 3’-O-sialyllactose 5.0 Water qs 100

Formulation 2 produces a deodorant effect.

The sodium salt compound of 3’-O-sialyllactose according to the invention is therefore compatible with aqueous formulations comprising water-soluble or water-dispersible active ingredients which are respectful of the skin.

Aqueous formulation 3:

ingredients % by mass relative to the total mass of the composition Crosslinked poly (acrylic acid) (Carbomer) 0.3 conservatives 1.0

Aluminum hydrochloride 50% 18.0 Aluminum chloride hexahydrate 50% 6.0 Sodium salt of 3’-O-sialyllactose 0.5 Water qs 100

Formulation 3 produces a deodorant and antiperspirant effect.

Aqueous formulation 4:

ingredients % by mass relative to the total mass of the composition Crosslinked poly (acrylic acid) (Carbomer) 0.3 conservatives 1.0 Aluminum hydrochloride 50% 15.0 Aluminum chloride hexahydrate 50% 8.0 Sodium salt of 3’-O-sialyllactose 5.0 Water qs 100

Formulation 4 produces a deodorant and antiperspirant effect.

The sodium salt compound of 3’-O-sialyllactose according to the invention is also compatible with formulas comprising other deodorant and / or antiperspirant active agents.

Claims (16)

1. Use of at least one compound of formula (I) below in which - X denotes an oxygen atom, a radical -CH (OR) - or a radical -CH2-; - Ri denotes a C5-C6 cycloalkyl radical substituted with at least one OR radical, - a C1-C6 alkyl radical, substituted by at least one OR radical, or - a radical -OR; - R2 denotes a - COOH radical or a --SO3H radical; - R3 denotes - an OR radical - an optionally substituted O-monosaccharide radical, or - an optionally substituted O-oligosaccharide radical, preferably an O-oligosaccharide comprising between 2 and 5 monosaccharides, more preferably an O-disaccharide radical; - R4 denotes an NHR ’radical or an OR radical; - R denotes a hydrogen atom or a protecting group for a hydroxyl function, in particular an acetyl or benzyl radical, - R 'denotes a hydrogen atom or a protective group of primary amine function, in particular an acetyl radical as well as its salts, its solvates and its optical and / or geometric isomers, including enantiomers and diastereoisomers, its racemates, alone or in mixture, for the treatment of bad body odors, in particular linked to perspiration, and in particular bad axillary odors. 2. Use according to claim 1, characterized in that the salts of the compounds of formula (I) are chosen from the metal salts Cu ²⁺ , Mn ²⁺ and Zn ²⁺ , the alkaline salts Li ⁺ , Na ⁺ and K ⁺ and the alkaline earth salts Ca ²⁺ and Mg ² +, preferably the alkaline salts such as Na ⁺ . 3. Use according to any one of the preceding claims, characterized in that Ri denotes a C1-C6 alkyl radical, comprising at least one substituent OR with R as defined in claim 1, preferably a C1-C4 alkyl radical such as propyl, said alkyl radical being substituted by at least one hydroxy radical, in particular Ri denotes a radical of formula - (CHOH) _n -CH2-OH with n = 1,2,3 or 4 and preferably n = 3. 4. Use according to any one of the preceding claims, characterized in that R denotes a hydrogen atom and R2 denotes a carboxy radical -COOH. 5. Use according to any one of the preceding claims, characterized in that R3 denotes an O-monosaccharide radical, in particular an O-galactose radical. 6. Use according to any one of claims 1 to 4, characterized in that R3 denotes an O-oligosaccharide radical, preferably an O-disaccharide radical, in particular an O-lactose radical optionally substituted by one or more group (s) ) amino NRaRb or by one or more groups -O- (CH2) _m -NRaRb, with m denoting an integer inclusive between 1 and 8, such as 6, and Ra and Rb, identical or different, representing i) an atom of hydrogen or v) a radical -CO-R'a in which R'a represents a (Ci-C6) alkyl group such as methyl, in particular R3 denotes lactose, N-acetyllactosamine or 1-O-aminohexyllactose . 7. Use according to any one of the preceding claims, characterized in that R4 denotes an NHR ’radical with R ′ denoting a hydrogen atom or an acetyl radical, in particular an acetyl radical. 8. Use according to any one of claims 1 to 6, characterized in that X denotes an oxygen atom, R denotes a hydrogen atom, R2 denotes a radical -COOH, R4 denotes a radical NHR 'with R' as defined in claim 1, in particular acetyl, and Ri denotes a C1-C6 alkyl radical comprising at least one hydroxy radical such as a radical of formula - (CHOH) _n -CH2-OH with n = 1,2,3 or 4 and preferably n = 3. 9. Use according to any one of the preceding claims, characterized in that the compound of formula (I) is chosen from 3'-O-sialyllactose, 3'-sialylgalactose, 3'-a-sialyl-N- acetyllactosamine and 1-O-aminohexyl 3'-sialyllactose as well as their salts, in particular their alkaline salts such as their sodium salt, their solvates and their optical isomers, including enantiomers and diastereoisomers, their racemics, alone or as a mixture, as a in particular, the compound of formula (I) is 3'-O-sialyllactose as well as its salts, in particular its alkaline salts such as its sodium salt, and its solvates. 10. Use according to any one of claims 1 or 2, characterized in that X denotes a methylene radical -CH2-, R denotes a hydrogen atom, R2 denotes a radical -COOH, R4 denotes a hydroxy radical. 11. Use according to the preceding claim, characterized in that X denotes a methylene radical -CH2-, R2 denotes a radical -COOH, R3, Ri and R4 denote OH and R denotes a hydrogen atom and the compound of formula (I ) is preferably quinic acid, its salts, in particular its alkaline salts such as its sodium salt, its solvates and its optical isomers, including enantiomers and diastereoisomers, its racemates, alone or as a mixture. 12. Use according to any one of the preceding claims, characterized in that the compound of formula (I) as well as its salts, its solvates and its optical and / or geometric isomers, including enantiomers and diastereoisomers, its racemates, alone or as a mixture, is used in a cosmetic composition in a content varying from 0.1% to 20% by weight, better varying from 0.2% to 15% by weight, better still varying from 0.5% to 10% by weight, relative to the total weight of the composition. 13. topical composition, preferably cosmetic, in particular deodorant and, if necessary antiperspirant, comprising as deodorant active agent at least one compound of formula (I) as defined according to any one of claims 1 to 11 as well as its salts, solvates and optical and / or geometric isomers, including 5 enantiomers and diastereoisomers, its racemates, alone or as a mixture, and at least one additional deodorant active different from the compounds of formula (I) and / or at least one antiperspirant active. 14. Composition according to claim 13, characterized in that the composition comprises a content of compound (s) of formula (I) varying from 0.1% to 20% in 10 weight, better varying from 0.2% to 15% by weight, better still varying from 0.5% to 10% by weight relative to the total weight of the composition. 15. Composition according to any one of claims 12 or 13, characterized in that the mass ratio of compound (s) of formula (I) / active (s) deodorant (s) additional (s) and / or active (s) antiperspirant (s) varies from 0.001 to 10, better varies from 0.01 to 5, Even better ranges from 0.02 to 1.0. 16. Composition according to any one of claims 12 to 14, characterized in that it comprises at least one antiperspirant active, and in particular chosen from aluminum and / or zirconium salts, and in particular from l aluminum chloride hexahydrate, aluminum hydrochloride and mixtures thereof. FRENCH REPUBLIC irai - I NATIONAL INSTITUTE PROPERTY INDUSTRIAL PRELIMINARY SEARCH REPORT based on the latest claims filed before the start of the search National registration number FA 850793 FR 1763366 EPO FORM 1503 12.99 (P04C14) DOCUMENTS CONSIDERED AS RELEVANT Relevant claim (s) Classification attributed to the invention by ΙΊΝΡΙ Category Citation of the document with indication, if necessary, of the relevant parts X X AT AT EP 0 985 408 A2 (BEIERSDORF AG [DE]) March 15, 2000 (2000-03-15) * paragraphs [0008] - [0022], [0055], , [0066] * EP 2 196 208 Al (TAKASAGO PERFUMERY 00 LTD [JP]) June 16, 2010 (2010-06-16) * paragraphs [0007], [0061] - [0061] * * claims * JP 2011 229536 A (0GAWA & C0 LTD) November 17, 2011 (2011-11-17) * the entire document * US 2003/152538 Al (PRETI GEORGE [US] ET AL) August 14, 2003 (2003-08-14) * the entire document * 1-16 1-16 1-16 1-16 A61K8 / 33 A61K8 / 41 A61K8 / 46 A61K8 / 49 A61K8 / 60 A61Q15 / 00 TECHNICAL AREAS SOUGHT (IPC) A61K A61Q Research Completion Date Examiner July 2, 2018 Paul Soto, Raquel CATEGORY OF DOCUMENTS CITED T: theory or principle underlying the invention E: patent document with an earlier date X: particularly relevant on its own at the filing date and which was not published until that date Y: particularly relevant in combination with a deposit or at a later date. other document of the same category D; cited in request A: technological background L: cited for other reasons O: unwritten disclosure P: interlayer document &: member of the same family, corresponding document ANNEX TO THE PRELIMINARY RESEARCH REPORT