Compositions comprising a compound of low solubility and a lipophilic amino acid derivative, and corresponding uses and processes
Abstract
Cosmetic or dermatological composition comprising, in a physiologically acceptable medium, at least one compound of low water solubility, that is, of water solubility at 25 ° C less than 1% by weight and such that deltaa> 6 J 1/2 cm - 3/2, said low water solubility compound being chosen from the salicylic acid derivatives of formula I '' or a monovalent, divalent salt or mixtures of derivatives of formula I '': ** see formula ** in which: R '' '' 1 represents a hydroxyl radical or an ester of the formula -O-CO-R '' '' 4 in which R '' '' 4 is an aliphatic, saturated or unsaturated radical, comprising from 1 to 26 carbon atoms and, preferably, from 1 to 18 carbon atoms, an amine or thiol function, optionally substituted by an alkyl radical comprising from 1 to 18 carbon atoms and, preferably, from 1 to 12 carbon atoms; R '' '' 2 and R '' '' 3 are, independently of each other, in one of the positions 3, 4, 5 or 6 of the benzene nucleus and represent, independently of each other, a hydrogen atom or a radical: - (O) n- (CO) m- R '' '' 5 in which n and m, independently of each other, are each an integer equal to 0 or 1, with the proviso that R '' '' 2 and R '' '' 3 are not simultaneously hydrogen atoms and R '' '' 5 represents a hydrogen; a saturated aliphatic radical comprising from 1 to 18 carbon atoms, linear, branched or cyclic; an unsaturated radical comprising from 3 to 18 carbon atoms, which carries from one to nine double bonds, conjugated or not, the radicals can be substituted by at least one substituent chosen from the halogen atoms (fluorine, chlorine, bromine, iodine ), the trifluoromethyl, hydroxyl radicals in free form or esterified by an acid comprising from 1 to 6 carbon atoms, or free or esterified carboxyl with a lower alcohol comprising from 1 to 6 carbon atoms; an aromatic radical comprising from 6 to 10 carbon atoms and at least one lipophilic amino acid derivative, which is an amino acid ester of the formula: wherein: n is an integer equal to 0, 1 or 2; R '' 1 (CO) N (R '' 2) CH (R '' 3) (CH2) n (CO) OR '' 4 R '' 1 represents an alkyl or alkenyl radical of 5 to 21 carbon atoms, linear or branched; R '' 2 represents a hydrogen atom or an alkyl group of 1 to 3 carbon atoms; R''3 represents a radical chosen in the group consisting of a hydrogen atom, a methyl group, an ethyl group, a linear or branched alkyl radical of 3 or 4 carbon atoms; R '' 4 represents an alkyl radical of 1 to 10 carbon atoms or alkenyl of 2 to 10 carbon atoms, linear or branched, or a sterol moiety. n

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10 claims: 6 independent, 4 dependent
- 1ES 2 320 103 T3 REIVINDICACIONES 1. Composición cosmética o dermatológica que comprende, en un medio fisiológicamente aceptable, al menos un compuesto de baja solubilidad en agua, es decir, de solubilidad en agua a 25°C inferior a 1% en peso y tal que da 6 J 1/2 cm -3/2 , siendo escogido dicho compuesto de baja solubilidad en agua entre los derivados de ácido salicílico de fórmula I’ o una sal monovalente, divalente o mezclas de derivados de fórmula I’:en la que: R” 1 representa un radical hidroxilo o un éster de fórmula -O - CO - R 4 en la cual R” 4 es un radical alifático, saturado o insaturado, que comprende de 1 a 26 átomos de carbono y, preferentemente, de 1 a 18 átomos de carbono, una función amina o tiol, eventualmente sustituida por un radical alquilo que comprende de 1 a 18 átomos de carbono y, preferentemente, de 1 a 12 átomos de carbono;R” 2 y R” 3 se encuentran, independientemente uno del otro, en una de las posiciones 3,4, 5 o 6 del núcleo bencénico y representan, independientemente uno del otro, un átomo de hidrógeno o un radical: -(O) n - (CO) m - R 5 en el cual n y m, independientemente uno del otro, son cada uno un entero igual a 0 o 1, con la condición de que R”2 y R”3 no sean simultáneamente átomos de hidrógeno y R” 5 representa un hidrógeno;un radical alifático saturado que comprende de 1 a 18 átomos de carbono, lineal, ramificado o cíclico;un radical insaturado que comprende de 3 a 18 átomos de carbono, que lleva de uno a nueve dobles enlaces, conjugados o no, pudiendo estar sustituidos los radicales por al menos un sustituyente escogido entre los átomos de halógeno (flúor, cloro, bromo, yodo), los radicales trifluorometilo, hidroxilo en forma libre o esterificada por un ácido que comprende de 1 a 6 átomos de carbono, o carboxilo libre o esterificado con un alcohol inferior que comprende de 1 a 6 átomos de carbono;un radical aromático que comprende de 6 a 10 átomos de carbono y al menos un derivado lipófilo de aminoácido, que es un éster de aminoácido de fórmula: R'i(CO)N(R , 2)CH(R , 3)(CH2)n(CO)OR , 4 en la que: n es un entero igual a 0, 1 o 2;R’1 representa un radical alquilo o alquenilo de 5 a 21 átomos de carbono, lineal o ramificado;R’2 representa un átomo de hidrógeno o un grupo alquilo de 1 a 3 átomos de carbono;R’3 representa un radical escogido en el grupo formado por un átomo de hidrógeno, un grupo metilo, un grupo etilo, un radical alquilo lineal o ramificado de 3 o 4 átomos de carbono;R’4 representa un radical alquilo de 1 a 10 átomos de carbono o alquenilo de 2 a 10 átomos de carbono, lineal o ramificado, o un resto esterol. ES 2 320 103 T3
- 2Composición según la reivindicación 1 tal que dicho éster de aminoácido es el N-lauroilsarconisato de isopropilo CH 3 - (CH 2 ) 10 CO - N(CH 3 ) - CH 2 - COO - CH - (CH 3 ) 2 .
- 3Composición según una cualquiera de las reivindicaciones 1 o 2 caracterizada porque dicho compuesto de baja solubilidad en agua representa de 0,001 a 30% en peso y preferentemente de 0,05 a 15% en peso, respecto del peso total de la composición.
- 4Composición según una cualquiera de las reivindicaciones 1 a 3, caracterizada porque dicho derivado lipófilo de aminoácido representa de 0,01 a 90% en peso, preferentemente de 0,1 a 50% en peso y, de forma aún más preferida, de 0,1 a 30% en peso, respecto del peso total de la composición.
- 5Composición según una de las reivindicaciones, en la cual el derivado de ácido salicílico se escoge entre los derivados n-octanoil-5-salicílico, n-decanoil-5-salicílico, n-dodecanoil-5-salicílico, n-octil-5-salicílico, n-heptiloxi-5-salicílico, n-heptiloxi-4-salicílico, 5-ter-octilsalicílico, 3-ter-butil-3-metilsalicílico, 3-ter-butil-6-metilsalicílico, 3,5-diisopropilsalicílico, 5-butoxisalicílico, 5-octiloxisalicílico, propanoil-5-salicílico, n-hexadecanoil-5-salicílico, n-oleoil5-salicílico, benzoil-5-salicílico, sus sales monovalentes y divalentes y sus mezclas.
- 6Composición según la reivindicación precedente, en la cual el derivado de ácido salicílico es el ácido n-octanoil5-salicílico.
- 7Composición según una de las reivindicaciones precedentes, en la cual el derivado de ácido salicílico representa de 0,001 a 15%, preferentemente de 0,1 a 5% en peso respecto del peso total de la composición.
- 8Utilización cosmética de la composición según una cualquiera de las reivindicaciones precedentes, para la protección, el cuidado, la limpieza y/o el maquillaje de la piel y/o de las mucosas y/o de las fibras queratínicas.
- 9Utilización de la composición según una cualquiera de las reivindicaciones 1 a 7 para la fabricación de una composición terapéutica dermatológica destinada a luchar contra los signos del envejecimiento cutáneo y/o luchar contra el acné y/o luchar contra los desórdenes cutáneos.
- 10Procedimiento de tratamiento cosmético para luchar contra los signos del envejecimiento cutáneo y/o mejorar la luminosidad y el brillo del tono del rostro y/o alisar la piel de la cara y/o del cuerpo y o tratar las arrugas y arruguitas de la piel y/o estimular el proceso de renovación epidérmica y/o despigmentar y/o blanquear la piel, que consiste en aplicar sobre la piel una composición cosmética según una cualquiera de las reivindicaciones 1
Independent claims10
174 paragraphs in 10 sections, as filed
ES 2 320 103 T3
DESCRIPTION
Compositions comprising a low solubility compound and a lipophilic amino acid derivative, corresponding uses and procedures.
The present invention relates to compositions based on lipophilic amino acid derivatives, their uses and a process for solubilizing at least one compound with low solubility in water.
It is known to use active ingredients in cosmetic and / or dermatological compositions, for example with a view to caring for the skin or trying to provide beneficial effects for it. But nevertheless. the use of some of these actives poses a problem, insofar as they are in crystalline form and are hardly soluble in water or not at all.
Thus, if they are introduced as they are in cosmetic and / or dermatological compositions, they remain in the state of crystals, which renders the use of the composition containing them ineffective for treating the skin.
Generally, it is possible to introduce some of them in hydroalcoholic form (water / ethanol), but the presence of alcohol is not always desirable, especially when applied to certain areas of the face, such as the eye contour.
Therefore, the need persists to be able to introduce compounds of low solubility in cosmetic and / or dermatological compositions, especially in the aqueous phase of such compositions.
By "low solubility" are understood here compounds such that it gives> 6 J<sup>1/2</sup> cm and having a solubility in water at 25 ° C of less than 1% by weight. Generally, a molecule is defined as insoluble in water from a certain percentage (here 1%) when, at the macroscopic level, a precipitate appears or the solution becomes cloudy, and, at the microscopic level, crystals appear.
As recalled in the work "Properties of Polymers" by DWVan Krevelen, 3<sup>to</sup> edition (Elsevier, 1990), page 200 et seq., the solubility of a compound in a given solvent is largely determined by its chemical structure.
The solubility parameter allows defining a molecule with respect to the interaction forces in which it participates.
This so-called “Hansen's” solubility parameter is obtained by the following equation:
<sup>d</sup> = <sup>d</sup>d<sup>2 + d</sup>p<sup>2 + d</sup>h<sup>2</sup> in which:
d<sub>d</sub> represents the dispersion forces at the moment of the collisions, called London forces or Van der Waals forces, which come from the formation of induced dipoles when molecular collisions occur:
dd = IFd / V d<sub>p</sub> represents the molecular polarization forces or Debye interaction forces, that is, the permanent dipole generated by the molecule considered when it is put into solution and is calculated by:
dp = (ZFp<sup>2</sup>)<sup>1/2</sup>/ V and d<sub>h</sub> represents the specific interaction forces, such as hydrogen, acid / base, donor / acceptor bonds, calculated by:
d<sub>h</sub> = (ZFh / V)<sup>1/2</sup>
The parameters d<sub>d</sub>, d<sub>p</sub> and d<sub>h</sub> are expressed in (J / cm<sup>3</sup>)<sup>1/2</sup>.
Each of the parameters d<sub>p</sub> and d<sub>h</sub> it is non-zero when the molecule considered comprises at least one heteroatom.
F<sub>d</sub>, F<sub>p</sub>, F<sub>h</sub> are the molar constants of the interaction forces of the groups of atoms that make up the molecules and V is the molar volume that can be determined by the Fedors method (Polymer Engineering and Science, February, 1974, Vol 14 n ° 2). V is the sum of the molar volumes of the radicals that make up the molecule under consideration; the V value is given in the Fedors article previously mentioned for most radicals.
ES 2 320 103 T3
To calculate the values of F<sub>d</sub>, F<sub>p</sub>, F<sub>h</sub> For a given molecule, it is enough to calculate the sum of the contributions of the radicals that make up that molecule. The values of F<sub>d</sub>, F<sub>p</sub>, F<sub>h</sub> they have been established for most radicals; DWVan Krevelen's "Properties of Polymers" cited above contains, in particular, tables presenting these values for numerous radicals.
In order to obtain an expression of the solubility in two components, it has also been defined:
δα<sup>2</sup> = δρ<sup>2</sup> + δ<sub>Η</sub><sup>2</sup> = δ<sup>2</sup> - δd<sup>2</sup> from where δα = (δρ<sup>2</sup> + δ<sub>Η</sub><sup>2</sup>)<sup>1/2</sup>
These notions of solubility and cohesion are defined in particular in the work: “Properties of Polymers” by DWVan Krevelen, 3<sup>to</sup> edition, (Elsevier, 1990) chapter 7 and in the article “A method for estimating both the solubility parameters and molar volumes of liquids” by RF Fedors , Polymer Engineering and Science, February 1974, vol. 14 n ° 2 p147-154.
In the sense of the present invention, the inventors have defined molecules with low solubility in water as those molecules that have a solubility in water at 25 ° C of less than 1% by weight and such that δa> 6 J<sup>1/2</sup> cm<sup>-3/2</sup>.
It is often necessary to be able to easily solubilize molecules of low water solubility in a physiologically acceptable medium. Generally, the solutions and compositions thus obtained are easy to use and can be applied with a minimum of discomfort. Furthermore, it is often necessary to be able to solubilize a sufficient quantity of these low solubility molecules for their cosmetic or dermatological use, without recrystallization of these molecules or loss of solubility of the composition containing them. Indeed, this instability would result in a more or less significant loss of efficacy of these compositions and / or a modification of their appearance, which would entail the risk that the user would stop using them.
The Applicant has now discovered that lipophilic amino acid derivatives made it possible to unexpectedly increase the solubilization of these low solubility molecules and keep those molecules solubilized in compositions that are indeed stable.
Therefore, the present invention has as its object a process for solubilizing at least one low solubility compound of formula (I '), said process comprising the essential step of mixing the low solubility compound with at least one lipophilic amino acid derivative, as well as a composition comprising, in a physiologically acceptable medium, at least one compound having a solubility in water at 25 ° C of less than 1% and such that δa> 6 J<sup>1/2</sup> cm<sup>-3/2</sup> of formula (I ') and at least one lipophilic amino acid derivative.
By "physiologically acceptable medium", in the sense of the present application, it is meant a medium that is compatible with the skin, including the scalp, mucous membranes, eyes and / or hair.
As an illustration, the lipophilic amino acid derivatives used in the sense of the present application have made it possible to solubilize:
- more than 20% aminophenol derivatives without recrystallization after three weeks at 25 ° C;
- more than 15% of derivatives of salicylic acid without recrystallization after three weeks at 25 ° C;
- about 4% of diosgenin acetate or hecogenin without recrystallization after 24 hours at 25 ° C.
In the case of use in an emulsion, the use of one of these lipophilic amino acid derivatives makes it possible to exceed the limit traditionally imposed by the solubilizer rate, the cosmeticity of these solubilizers being generally an obstacle. Within the framework of the present invention, the emulsions maintain a very acceptable cosmeticity, despite the high levels of solubilizer.
The lipophilic amino acid derivative used according to the invention is an amino acid ester of the formula:
R 'i (CO) N (R' 2) CH (R3) (CH2) n (CO) OR'4 where:
n is an integer equal to 0, 1 or 2;
R '<sub>1</sub> represents an alkyl or alkenyl radical of 5 to 21 carbon atoms, linear or branched;
ES 2 320 103 T3
R '<sub>2</sub> represents a hydrogen atom or an alkyl group of 1 to 3 carbon atoms;
R '<sub>3</sub> represents a radical chosen from the group consisting of a hydrogen atom, a methyl group, an ethyl group, a linear or branched alkyl radical of 3 or 4 carbon atoms;
R '<sub>4</sub> represents an alkyl radical of 1 to 10 carbon atoms or alkenyl of 2 to 10 carbon atoms, linear or branched, or a sterol radical.
Preferably, the group R '<sub>1</sub>(CO) - is an acyl group of an acid chosen from the group consisting of capric, lauric, myristic, palmitic, stearic, behenic, linoleic, linolenic, oleic, isostearic, 2-ethylhexanoic acids, coconut oil fatty acids and palm kernel oil fatty acids. Furthermore, these fatty acids can have a hydroxyl group. Even more preferably, it will be lauric acid.
The part -N (R '<sub>2</sub>) CH (R '<sub>3</sub>) (CH<sub>2</sub>)<sub>n</sub>(CO) - of the amino acid ester is preferably chosen from the following amino acids: glycine, alanine, valine, leucine, isoleucine, serine, threonine, proline, hydroxyproline, // - alanine, aminobutyric acid, aminocaproic acid, sarcosine or N-methyl -d-alanine.
Even more preferably, it will be sarcosine.
The part of the amino acid esters that corresponds to the group OR '<sub>4</sub> It can be obtained from alcohols chosen from the group consisting of: methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, isobutanol, 3-methyl-1-butanol, 2-methyl-1-butanol, fusel oil, pentanol, hexanol, cyclohexanol, octanol, 2-ethylhexanol, decanol, lauryl alcohol, myristic alcohol, cetyl alcohol, ketosterol alcohol, stearyl alcohol, oleic alcohol, behenyl alcohol, jojoba alcohol, 2-hexadecyl alcohol, 2-octyldodecanol, and isosterol alcohol.
In particular, these amino acid esters can be obtained from natural sources of amino acids. In this case, the amino acids come from the hydrolysis of natural vegetable proteins (oats, wheat, soybeans, palm, coconut) and then necessarily lead to amino acid mixtures that must then be esterified and then Nazylated. In particular, the preparation of such amino acids is described in patent application FR 2 796 550.
The most especially preferred amino acid ester for use in the present invention is isopropyl N-lauroylsarcosinate, of the formula:
CH<sub>3</sub> - (CH2) ioCO - N (CH<sub>3</sub>) - CH2 - COO - CH2 - (CH<sub>3</sub>)2.
The amino acid esters used preferably in the sense of the present invention, as well as their synthesis, are described in patent applications EP 1 044 676 and EP 0 928 608 of the company AJINOMOTO CO.
In general, the lipophilic amino acid derivative or derivatives represent 0.01 to 90% by weight, preferably 0.1 to 50% by weight, and even more preferably 0.1 to 30% by weight , with respect to the total weight of the composition.
Compounds of low solubility in water, in the sense of the present invention, are derivatives of salicylic acid.
In general, the low solubility compound represents 0.001 to 30% by weight, and preferably 0.05 to 15% by weight, relative to the total weight of the composition.
In the sense of the present application, the derivatives of salicylic acid of low solubility are the derivatives of formula I 'or the monovalent, divalent salts or the mixtures of these derivatives:
COOH
<img file="ES2320103T3_D0001.tif" />
(Γ)
ES 2 320 103 T3 in which:
R "<sub>1</sub> represents a hydroxyl radical or an ester of the formula
-O - CO - R4 in which R "<sub>4</sub> is an aliphatic radical, saturated or unsaturated, comprising from 1 to 26 carbon atoms and, preferably, from 1 to 18 carbon atoms, an amine or thiol function, optionally substituted by an alkyl radical containing from 1 to 18 carbon atoms. carbon and preferably 1 to 12 carbon atoms;
R "<sub>2</sub> and R "<sub>3</sub> They are found, independently of each other, in one of the 3,4, 5 or 6 positions of the benzene nucleus and represent, independently of each other, a hydrogen atom or a radical:
-(OR)<sub>n</sub> - (CO)<sub>m</sub> - R<sub>5</sub> in which n and m, independently of each other, are each an integer equal to 0 or 1, provided that R "2 and R" 3 are not simultaneously hydrogen atoms and R "<sub>5</sub> represents a hydrogen; a saturated aliphatic radical comprising 1 to 18 carbon atoms, linear, branched or cyclic; an unsaturated radical comprising from 3 to 18 carbon atoms, bearing from one to nine double bonds, conjugated or not, the radicals being able to be substituted by at least one substituent chosen from halogen atoms (fluorine, chlorine, bromine, iodine ), trifluoromethyl, hydroxyl radicals in free form or esterified by an acid containing 1 to 6 carbon atoms, or carboxyl free or esterified with a lower alcohol comprising 1 to 6 carbon atoms or an aromatic radical comprising 6 to 10 carbon atoms.
Preferably, the salicylic acid derivative is such that R "<sub>5</sub> represents a saturated aliphatic radical comprising from 3 to 15 carbon atoms.
Preferably, the salicylic acid derivative is such that R "1 represents a hydroxyl radical.
Preferably, the salicylic acid derivative is such that R "3 is at the 5-position of the benzene nucleus and R" 2 represents a hydrogen atom.
According to a preferred embodiment of the invention, the salicylic acid derivative is chosen from the derivatives n-octanoyl-5-salicylic, n-decanoyl-5-salicylic, n-dodecanoyl-5-salicylic, n-octyl-5- salicylic, n-heptyloxy-5-salicylic, n-heptyloxy-4-salicylic, 5-tert-octylsalicylic, 3-tert-butyl-5-methylsalicylic, 3-tert-butyl-6-methylsalicylic, 3,5-diisopropylsalicylic, 5-butoxysalicylic, 5-octyloxysalicylic, propanoyl-5-salicylic, n-hexadecanoyl-5-salicylic, n-oleoyl-5-salicylic, benzoyl-5-salicylic, its monovalent and divalent salts and their mixtures.
According to another preferred embodiment, the compositions comprise a salt of the salicylic acid derivative of formula I ', chosen from salts of strontium, calcium, magnesium, barium and manganese. Even more preferably, this salt of the salicylic acid derivative is chosen from the strontium salt of 5-octanoylsalicylic acid, the calcium salt of 5-octanoylsalicylic acid, the magnesium salt of 5-octanoylsalicylic acid and their mixtures.
These derivatives are known in the prior art; In particular, patent application EP 662 318 refers to the use of such salicylic acid derivatives to manufacture cosmetic and / or dermatological compositions for the treatment of the body and face, especially for the treatment of acne and skin aging. skin. Patent applications EP 0 662 318 and EP 987 011 describe processes for the preparation of such salicylic acid derivatives.
Derivatives of salicylic acid are of great interest, especially to prevent or repair the main manifestations of skin aging, which are wrinkles and wrinkles, disorganization of the "grain" of the skin, modification of the color or tone of the skin and the loss of firmness and tonicity of it. However, the use of these derivatives poses a problem, insofar as, when they are introduced as such in the topical compositions, they do not solubilize and remain in the state of crystals, which makes the use of the composition containing them ineffective. for skin treatment.
Generally, these derivatives are used in solution in lower alcohols such as ethanol or isopropanol or in solvents such as octyldodecanol, certain glycols and short-chain fatty alcohols (chains with less than 12 carbon atoms). However, these lower alcohols have the drawback of drying out and irritating the skin; consequently, it is preferred to avoid its use in body and / or face care products. In addition, these solubilizers can only be introduced in small amounts under penalty of altering the cosmetic qualities (drying of the skin) and the stability of the compositions containing them.
The concentration of salicylic acid derivatives of the composition according to the present invention is between 0.001 and 15% by weight, preferably between 0.1 and 5% by weight, relative to the total weight of the composition. The
ES 2 320 103 T3 amount of amino acid esters will depend on the amount of salicylic acid derivatives to be solubilized. It may be between 0.01 and 90% by weight, and preferably between 0.1 and 50% by weight, relative to the total weight of the composition.
The composition according to the invention comprising at least one salicylic derivative can be used as a cosmetic or dermatological composition and, especially, for the care, protection, cleaning and / or make-up of keratin materials of human beings (skin, lips, keratin fibers such as hair and eyelashes) and, especially, to fight against the signs of skin aging and / or to smooth the skin of the face and / or body and / or to treat wrinkles and fine lines of the skin and / or to stimulate the epidermal renewal process and / or to depigment and skin whitening and / or to treat acne and / or to treat skin disorders.
By skin disorders are understood, in particular: the area, burns, eczema, demodecia, skin ulcer, fibrosis, control of scarring, psoriasis, pruritus, dermatitis, ichthyosis, corns and warts
Likewise, the invention also has for its object the cosmetic use of the cosmetic composition as previously defined for the protection, care, cleaning and / or make-up of the skin and / or mucosa and / or fibers. keratin.
The invention also has as its object a cosmetic treatment method for the protection, care, cleaning and / or makeup of the skin and / or mucous membranes and / or keratin fibers, which consists of applying on the skin and / or mucous membranes and / or keratin fibers the composition according to the invention.
The invention also has as its object a cosmetic treatment method to combat the signs of skin aging and / or improve the brightness of the tone or color and / or smooth the skin of the face and / or body and / or treat wrinkles and wrinkles of the skin and / or to stimulate the epidermal renewal process and / or to depigment and / or whiten the skin, which consists in applying the composition containing a derivative of salicylic acid according to the invention to the skin.
Another object of the invention is the use of the composition according to the invention for the manufacture of a dermatological therapeutic composition intended to combat the signs of skin aging and / or to combat acne and / or to combat skin disorders.
The salicylic acid derivative / amino acid ester weight ratio is preferably 0.001 / 99.999 to 35/65 and preferably 0.1 / 99.9 to 30/70.
The cosmetic composition according to the present invention can be presented in the forms normally used in cosmetics.
It can be presented in all the forms normally used for topical application, especially in the form of a hydroalcoholic solution, an oil-in-water or water-in-oil or multiple emulsion, an oily gel or a liquid, pasty or solid anhydrous product. or in the form of a dispersion in the presence of spherules, these spherules being polymeric nanoparticles such as nanospheres or nanocapsules or ionic or non-ionic lipid vesicles. These compositions are prepared according to the usual methods.
This composition can be more or less fluid and have the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste and a foam. Eventually, it can be applied to the skin or hair in the form of a spray. Likewise, it can be presented in solid form and, for example, in the form of a bar or stick.
In a known manner, the cosmetic and dermatological compositions according to the invention can also contain the usual adjuvants in the cosmetic and dermatological fields, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active ingredients, preservatives, antioxidants, solvents, perfumes, fibers, fillers, filters. , pigments, odor absorbers and coloring matters. The amounts of these various adjuvants are those conventionally used in the fields considered and, for example, from 0.01% to 50% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase, into the aqueous phase, into lipid vesicles and / or into nanoparticles.
Naturally, the person skilled in the art will be careful when choosing these possible complementary compounds, active or non-active, and / or their quantity, in such a way that the advantageous properties of the derivatives with low solubility are not altered by the planned addition. , or are not sensitively.
When the composition according to the invention is an emulsion, the proportion of the fatty phase can range from 0.5 to 80% by weight, and preferably from 5 to 50% by weight, relative to the total weight of the composition. The oils, emulsifiers and co-emulsifiers used in the composition in emulsion form are chosen from those conventionally used in the field under consideration.
ES 2 320 103 T3
The fatty phase or oily phase usually contains at least one oil. As oils usable in the composition of the invention, the following may be mentioned, for example:
- hydrocarbon oils of animal origin, such as perhydrosqualene;
- hydrocarbon oils of vegetable origin, such as liquid triglycerides of fatty acids having 4 to 10 carbon atoms, such as triglycerides of heptanoic or octanoic acids or also, for example, sunflower, corn, soybean oils, pumpkin, grape seeds, sesame, hazelnut, apricot, macadamia, spider, sunflower, castor bean, avocado; triglycerides of caprylic / capric acids, such as those sold by the Stearineries Dubois company or those sold under the names Miglyol 810, 812 and 818 by the Dynamit Nobel company; jojoba oil; shea butter oil;
- synthetic esters and ethers, especially of fatty acids, such as oils of formulas R<sup>6</sup>COOR<sup>7</sup> and R<sup>6</sup>OR<sup>7 </sup>in which R<sup>6</sup> represents the remainder of a fatty acid having 8 to 29 carbon atoms and R<sup>7</sup> represents a branched or unbranched hydrocarbon chain containing 3 to 30 carbon atoms, such as Purcellin oil, isononyl isononanoate, isopropyl myristate, ethyl-2-hexyl palmitate, octyl-2-dodecyl stearate , octyl-2-dodecyl erucate, isostearyl isoestaearate; hydroxylated esters such as isostearylactate, octylhydroxystearate, octyldodecyl hydroxystearate, diisotearylmalate, triisocetyl citrate, the fatty alcohol heptanoates, octanoates and decanoates; polyol esters such as propylene glycol dioctanoate, neopentyl glycol diheptanoate, and diethylene glycol diisononanoate; and pentaerythritol esters such as pentaerythrityl tetraisostearate;
- linear or branched hydrocarbons, of mineral or synthetic origin, such as paraffin oils, volatile or non-volatile, and their derivatives, petrolatum, polydecenes, hydrogenated polyisobutene, such as parleam oil;
- fatty alcohols having 8 to 26 carbon atoms, such as cetyl and stearyl alcohols and their mixture (cetylstearyl alcohol); octyldodecanol, 2-butyloctanol, 2-hexyldecanol, 2-undecylpentadecanol, oleic or linoleic alcohols;
- alkoxylated and especially ethoxylated fatty alcohols, such as oleth-12;
- partially hydrocarbon and / or silicone fluorinated oils such as those described in patent document JP-A-2 295912. As fluorinated oils, mention may also be made of perfluoromethylcyclopentane and perfluoro-1,3-dimethylcyclohexane, sold under the names "FLUTEC PC1®" and "FLUTEC PC3®" by the company BNFL Fluorochemicals; perfluoro-1,2-dimethylcyclobutane; perfluoroalkanes such as dodecafluoropentane and tetradecafluorohexane, sold under the names “PF 5050<sup>®</sup>"And" PF 5060® "by the company 3M or even also bromoperfluorooctyl sold under the name" FORALKYL® "by the company Atochem; nanofluoromethoxybutane sold under the name "MSX 4518®" by the company 3M and nanofluoroethoxyisobutane; perfluoromorpholine derivatives, such as 4-trifluoromethylperfluoromorpholine sold under the name “PF 5052<sup>®</sup>"By the 3M company;
- silicone oils such as polymethylsiloxanes (PDMS), volatile or not, with a linear or cyclic silicone chain, liquid or pasty at room temperature, especially cyclopolydimethylsiloxanes (cyclomethicones) such as cyclohexasiloxane; polydimethylsiloxanes having alkyl, alkoxy or phenyl groups, hanging from the silicone chain or at its end, groups having from 2 to 24 carbon atoms; phenylated silicones such as phenyltrimethicones, phenyldimethicones, phenyltrimethylsiloxydiphenylsiloxanes, diphenyldimethicones, diphenylmethyldiphenyltrisiloxanes, 2-phenylethyltrimethyl-siloxysilicates, polymethyl-phenylsiloxanes; and their mixtures.
By "hydrocarbon oil" is understood in the list of oils mentioned previously, any oil that contains mostly carbon and hydrogen atoms and, optionally, ester, ether, fluorinated, carboxylic acid and / or alcohol groups.
The other fatty substances that may be present in the oily phase are, for example, fatty acids having 8 to 30 carbon atoms, such as stearic, lauric, palmitic and oleic acids; waxes such as lanolin, beeswax, carnauba or candelilla waxes, paraffin waxes, lignite or microcrystalline waxes, ceresin or ozokerite, synthetic waxes such as polyethylene waxes, Fischer-Tropsch waxes; rubbers such as silicone rubbers (dimethiconol); silicone resins such as trifluoromethyl-alkyldimethicone (alkyl groups of 1 to 4 carbon atoms) and trifluoropropyldimethicone; and silicone elastomers such as products marketed under the names "KSG" by the company Shin-Etsu, with the names "Trefil", "BY29" or "EPSX" by the company Dow Corning or with the name "Gransil" by the company Grant Industries.
These fatty substances can be chosen in various ways by the person skilled in the art in order to prepare a composition having the desired properties, for example consistency or texture. The emulsions can contain at least one emulsifier chosen from amphoteric, anionic, cationic or non-ionic emulsifiers, used alone or in admixture.
ES 2 320 103 T3
When the composition is an emulsion, it generally contains at least one emulsifier. The emulsifiers are suitably chosen according to the emulsion to be obtained, whether it is water in oil (W / O) or oil in water (O / W).
For O / W emulsions, for example, a non-ionic emulsifier such as bear esters and ethers (monosaccharides) such as sucrose stearate, sucrose cocoate and the mixture of sorbitan stearate and cocoate cocoate can be used as the emulsifier. sucrose sold by the company ICI under the name Arlatone 2121<sup>®</sup>; polyol esters, especially glycerol or sorbitol, such as glyceryl stearate, polyglyceryl-2 stearate and sorbitan stearate; glycerol ethers; the oxyethylenated and / or oxypropylene ethers such as the oxyethylenated or oxypropylene ether of lauric alcohol with 25 oxyethylenated groups and 25 oxypropylene groups (CTFA name "PPG-25 laureth-25") and the oxyethylene ether of the mixture of fatty alcohols from 12 to 15 carbon atoms having 7 oxyethylenated groups (CTFA name "C12-C15 Pareth-7"); ethylene glycol polymers, such as PEG-100 and mixtures thereof.
For W / O emulsions, mention may be made as emulsifiers, for example, of fatty esters of polyols, especially glycerol or sorbitol, and in particular isostearic, oleic and ricinoleic esters of polyols, such as the petrolatum mixture. , from polyglyceryl oleate-3, from glyceryl isostearate; hydrogenated castor oil and ozokerite, sold under the name PROTEGIN W® by the company Goldschmidt, sorbitan isostearate, polyglyceryl di-isostearate; polyglyceryl-2 sesqui-isostearate; bear esters and ethers such as "methylglucose dioleate"; fatty esters such as magnesium lanolate; dimethicone-copolyols and alkyl-dimethiconecopolyols, such as laurylmethicone-copolyol sold under the name DOW CORNING 5200 FORMULATION AID by the company Dow Corning and cetyldimethicone-copolyol sold under the name ABIL EM 90® by the company Goldschmidt and their mixtures.
The emulsifiers can be introduced as such or as a mixture with other emulsifiers and / or with other compounds, such as fatty alcohols or oils.
As active ingredients that can be used in the composition of the invention, there may be mentioned for example: moisturizing agents and, for example, hydrolysates of proteins and polyols such as glycerin, glycols such as polyethylene glycols and sugar derivatives; natural extracts; procyanidol oligomers; vitamins such as vitamin A (retinol), vitamin C (ascorbic acid), vitamin E (tocopherol), vitamin B5 (panthenol), and vitamin B3 (niacinamide); vitamin K; urea; caffeine; depigmenting agents such as kojic acid and caffeic acid; salicylic acid (for compositions that no longer contain a salicylic acid derivative); alpha-hydroxy acids such as lactic and glycolic acids; retinoids such as carotenoids; sun filters; fillers, pigments, colorants, keratolytic agents, preservatives, antioxidants, perfumes, hydrocortisone; melatonin; extracts of algae, fungi, vegetables, yeasts, bacteria; hydrolyzed, partially hydrolyzed, or non-hydrolyzed proteins; enzymes; antibacterial active ingredients for the treatment of oily skin such as 2,4,4'-trichloro-2'-hydroxy-diphenyl-ether (or triclosan), 3,4,4'-trichlorocarbanilide (or triclocarban), azelaic acid, benzoyl peroxide; mattifying agents, such as fibers; tensioning agents; optical brighteners and their mixtures, such as vitamin mixtures (A and C or A + C + E, for example).
The active or active ingredients may be present in a concentration ranging from 0.01 to 20%, preferably from 0.1 to 10% and better from 0.5 to 5% of the total weight of the composition.
Examples
In the following table, molecules of low solubility in water are presented, in the sense of the present invention; are poorly soluble in water, especially at room temperature and have a day> 6J<sup>1/2</sup> cm<sup>-3/2</sup>.
<td></td><td>Solubility in water at 25 ° C</td><td>óa in j'icm '<sup>3</sup>'<sup>2</sup></td>
<td>N-ethoxycarbonyl-para-aminophenol</td><td rowspan="7"> < 1 %</td><td> 16.1</td>
<td>N-cholesteryloxycarbonyl-para-aminophenol *</td><td> 8.7</td>
<td>(3beta, 5alpha, 25r) -3-hydroxyspirostan-12-one (hecogenin acetate) *</td><td> 6.7</td>
<td>5-spirostan-3-beta-ol (diosgenin) '</td><td> 8.6</td>
<td>n-octanoyl-5-salicylic acid</td><td> 11.3</td>
<td>DHEA *</td><td> 9.9</td>
<td>2-amino-4-dodecylaminopyrimidine-3-oxide *</td><td> 8.9</td>
Examples outside the invention
ES 2 320 103 T3
The examples that follow illustrate the invention without limiting its scope.
- Simple solubility
Protocol: derivatives of low water solubility are weighed and placed in an airtight pillbox. The required amount of solvent is added. The suspension is stirred (magnetic stirring) at 80 ° C for 1 h at the most.
The following table indicates the dissolution or non-dissolution of the active, as well as its evolution over time.
The non-solubility of the active in the solvent is characterized macroscopically by a precipitate or simply by a cloudy solution and microscopically by the presence of crystals.
The solvent used is isopropyl N-lauroyl-sarcosinate.
<td>Definition</td><td>Rate</td><td>Solubilization to TO</td><td>Stability over time at 25 ° C</td>
<td rowspan="2">N-cholesteryloxy-carbonyl-para-aminophenol</td><td> 5%</td><td rowspan="2"></td><td>Clear for 7 days</td>
<td> 9%</td><td>Clear for 4 days</td>
<td rowspan="4">N-ethoxycarbonyl-para-aminophenol</td><td> 5%</td><td rowspan="4">No recrystallization</td><td>Clear for 18 days</td>
<td> 20%</td><td>Clear for 6 days</td>
<td> 23%</td><td>Clear for 6 days</td>
<td> 26%</td><td>Clear for 1 day</td>
<td>DHEA</td><td> 20%</td><td>No recrystallization</td><td> -</td>
<td>2-amino-4-dodecylaminopyridine-3-oxide</td><td> 1%</td><td>No recrystallization</td><td>Clear for 1 day</td>
<td>Diosgenin</td><td> 2%</td><td>No recrystallization</td><td>Clear for 3 weeks</td>
<td>Hecogenin acetate</td><td> 2%</td><td>No recrystallization</td><td>Clear for 1 day</td>
<td rowspan="3">N-octanoyl-5-salicylic acid</td><td> 5%</td><td rowspan="3">No recrystallization</td><td>Clear for 7 days</td>
<td> 9%</td><td>Clear for 4 days</td>
<td> 27%</td><td>Limpid</td>
- Use in emulsion
The solubilization of the active ingredients by the previously mentioned solvents (solubilizers) has been verified in emulsion, thus making it possible to formulate stable compositions.
The emulsions made are O / W emulsions, using Simulsol 165 as surfactant (mixture of glyceryl stearate and PEG-100 stearate).
The physicochemical stability of the emulsions is verified by macroscopic, microscopic, pH and viscosity control, after 24 hours and over time. The composition according to the present invention can be presented in the forms normally used in cosmetics.
ES 2 320 103 T3
Examples of compositions
<td> ¡</td><td></td><td colspan="2">N-octanoyl-5 salicylic acid</td>
<td>'phase 1</td><td>CTFA name</td><td>Example according</td><td>Comparative example</td>
<td> |</td><td>Preservative</td><td> 0,2</td><td> 0.2</td>
<td rowspan="3">í TO</td><td>Disodium EDTA</td><td> 0,15</td><td> 0,15</td>
<td>Glycerin</td><td> 3</td><td> 3</td>
<td>Water</td><td>csp 100</td><td>csp 100</td>
<td rowspan="4">B</td><td>Glyceryl stearate and PEG-100 stearate</td><td> 0,3</td><td> 0.3</td>
<td>Aicohoi cetüico</td><td> 0,4</td><td> 0,4</td>
<td>Preservative</td><td> 0,1</td><td> 0,1</td>
<td>Triclosan</td><td> 0,1</td><td> 0.1</td>
<td rowspan="4">C</td><td>N-cholesterylcarbonit-para-aminophenol</td><td> -</td><td> -</td>
<td>N-ethoxycarbonyl-paraamino-phenol</td><td> -</td><td> -</td>
<td>N-octanoyl-5-salicylic acid</td><td> 1</td><td> 1</td>
<td>Isopropyl lauroylsarcosinate</td><td> 10</td><td> -</td>
<td rowspan="2">D</td><td>Cross-linked polymer (acrylates and alkylacrylate with alkyl groups of 10 to 30 carbon atoms)</td><td> 0,5</td><td> 0,5</td>
<td>Cyclohexasiloxane</td><td> 5</td><td> 5</td>
<td>AND</td><td>Water</td><td> 10</td><td> 10</td>
<td></td><td>Alcohol</td><td> 5</td><td> 5</td>
<td>F</td><td>Polyacrylamide and isoparaffin of 13-14 carbon atoms and laureth-7</td><td> 1</td><td> 1</td>
<td>θ</td><td>Triethanolamine</td><td> 1,03</td><td> 1,03</td>
<td></td><td>Water</td><td> 7</td><td> 7</td>
Operative mode
Phase a
It is heated to 85 ° C. Stir to solubilize preservatives. The temperature is then lowered to 75 ° C to make the emulsion.
Phase b
Heat to 75 ° C and homogenize until complete dissolution. Making the emulsion: B is poured into A at 75 ° C with stirring for 15 minutes.
Phase C
It is homogenized until complete dissolution at 30 ° C and added to the emulsion (A + B) at 60 ° C.
PhaseD
It is dispersed at room temperature and added to the emulsion (A + B + C) at 60 ° C. It is homogenized.
ES 2 320 103 T3
Phases E, F and G
They are prepared at room temperature, then they are added to the emulsion (A + B + C + D) at 40 ° C and everything is homogenized with stirring.
The emulsion is allowed to cool to 25 ° C.
It has been shown that the solubilization of derivatives of low solubility by amino acid esters is perfectly achievable in emulsion, in order to confirm that it is possible to formulate stable cosmetic compositions containing such derivatives.
The previously made emulsions are oils in water with Simulsol 165 marketed by the company SEPPIC as a surfactant; Simulsol 165 is a mixture of glyceryl stearate and PeG-100 stearate.
The physicochemical stability of the emulsions is verified by macroscopic, microscopic, pH and viscosity control, after 24 hours.
<td></td><td>With 10% isopropyl N-lauroylsarcosinate (compliant)</td><td>Without N-lauroylsarcosinate isopropyl</td>
<td>1% n-octanoyl- acid 5-salicylic</td><td>Example Crystal-free emulsion, remains compliant for up to 2 months at 4/25 and 45 ° C</td><td>Comparative example. Fine emulsion with crystals from T = 24 hours</td>
The compositions according to the invention do not contain crystals and are stable over time and when the temperature varies, while the compositions of the comparative examples show crystals from 24 hours after their preparation.
Contents10
1 sheet
Sheet 1
20 members in 8 offices
Priority claims20
| Document | Office | Kind | Date |
|---|---|---|---|
| 0108428 | France | A | |
| 0108428 | France | A | |
| 0108429 | France | A | |
| 0108429 | France | A | |
| 0108430 | France | A | |
| 0108430 | France | A | |
| 0108431 | France | A | |
| 0108431 | France | A | |
| 20010008428 | France | – | |
| 20010008429 | France | – | |
| 20010008430 | France | – | |
| 20010008431 | France | – | |
| 0108429 | – | – | – |
| 0108430 | – | – | – |
| 0108431 | – | – | – |
| 022914810108428 | – | – | – |
| FR20010008428 | – | – | – |
| FR20010008429 | – | – | – |
| FR20010008430 | – | – | – |
| FR20010008431 | – | – | – |
Members20
| Document | Office | Kind | |
|---|---|---|---|
| FR2826271A1 | France | A1 | |
| FR2826272A1 | France | A1 | |
| FR2826273A1 | France | A1 | |
| FR2826275A1 | France | A1 | |
| EP1269986A2 | European Patent Office (EPO) | A2 | |
| CN1394594A | China | A | |
| US2003027864A1 | United States of America | A1 | |
| KR20030015825A | Republic of Korea | A | |
| EP1269986A3 | European Patent Office (EPO) | A3 | |
| JP2003128513A | Japan | A | |
| FR2826271B1 | France | B1 | |
| FR2826272B1 | France | B1 | |
| FR2826273B1 | France | B1 | |
| FR2826275B1 | France | B1 | |
| JP3746255B2 | Japan | B2 | |
| KR100546018B1 | Republic of Korea | B1 | |
| US7485315B2 | United States of America | B2 | |
| EP1269986B1 | European Patent Office (EPO) | B1 | |
| DE60231272D1 | Germany | D1 | |
| ES2320103T3This record | Spain | T3 |
Numbers
- Publication
- 2320103
- Publication, DOCDB
- 2320103
- Publication, EPODOC
- ES2320103T
- Application
- 2291481
- Application, DOCDB
- 02291481
- Application, EPODOC
- ES20020291481T
Titles2
- Spanish
- COMPOSICIONES QUE COMPRENDEN UN COMPUESTO DE BAJA SOLUBILIDAD Y UN DERIVADO LIPOFILO DE ACIDO AMINADO, UTILIZACIONES Y PROCEDIMIENTOS CORRESPONDIENTES.
- English
- COMPOSITIONS THAT INCLUDE A COMPOUND OF LOW SOLUBILITY AND A LIPOFIL ACID DERIVATIVE OF AMINATED ACID, USES AND CORRESPONDING PROCEDURES.
Classification
- CPC, 15
- A61K8/37
- A61Q19/08
- A61K8/40
- A61K8/44
- A61K8/4953
- A61K8/63
- A61K31/506
- A61K31/5685
- A61K31/616
- A61K2800/59
- A61Q5/08
- A61Q19/00
- A61Q19/02
- A61P17/00
- A61P17/10
- IPC, 23
- A61K8 30
- A61K31 506
- A61K8 00
- A61K8 04
- A61K8 14
- A61K8 33
- A61K8 37
- A61K8 40
- A61K8 44
- A61K8 49
- A61K8 63
- A61K31 5685
- A61K31 616
- A61P17 00
- A61P17 10
- A61Q1 00
- A61Q1 02
- A61Q5 00
- A61Q5 08
- A61Q19 00
- A61Q19 02
- A61Q19 08
- A61Q19 10