ES2315119A1 - Use of derivatives 2.5 -dihidrocibencenicos in the manufacture of medicines and cosmetics (Machine-translation by Google Translate, not legally binding) - Google Patents

Abstract

Use of 2,5-dihydroxybenzene derivatives in the manufacture of medicines and cosmetics. This invention relates to a cosmetic product based on 2,5-dihydroxybenzenic derivatives comprising the formula i, for the treatment of obesity (excessive adipogenesis), of atopic dermatitis, of contact dermatitis, of viral warts and for the prevention and treatment of skin photo-aging due to exposure to ultraviolet b (uvb) rays, particularly to sun rays, and for skin pathologies and wrinkles associated with said photoaging of the skin such as actinic keratosis, hyperpigmentation and seborrheic keratosis, as well as for the treatment of hirsutism, hypertrichosis or as anti-adipogenic in the treatment of obesity (excessive adipogenesis). The present invention also relates to applications of 2,5-dihydroxybenzenic derivatives comprising 2,5-dihydroxybenzenesulfonic acid, gentisic acid or homogentisic acid or its salts or esters. (Machine-translation by Google Translate, not legally binding)

Description

Use of derivatives 2,5-dihydroxybenzene in the manufacture of Medicines and cosmetics

Field of the Invention

This invention relates to the use of derivatives 2,5-dihydroxybenzene in the preparation of medicines or cosmetics useful for prevention and treatment of skin aging due to exposure to lightning ultraviolet B (UVB), or exposure to sunlight in general, for the treatment of the pathologies associated with said skin photoaging such as skin wrinkles, keratosis actinic and seborrheic, skin pigmentation and hyperpigmentation cutaneous, as well as for the treatment of hirsutism and hypertrichosis, obesity or excessive adipogenesis, of the atopic dermatitis and / or contact dermatitis and the treatment of viral warts

Background of the invention

Chronic exposure to ultraviolet B rays (UVB: 290-320 nm wavelength), or at solar rays in general (comprising, among other lengths of wave, that of UVB radiation), produces aging on the skin (photoaging) due to cumulative damage to DNA and structural proteins of the skin, manifesting itself in the form of fine wrinkles, laxity with loss of skin elasticity, elastosis, yellowing with focused areas of melanic hyperpigmentation (solar, actinic or old age lentigo). In addition, skin photoaging is associated with the appearance of comedones that acquire their maximum expression in the complexion romboidalis of the neck The histological examination can be seen atrophy epidermal and degenerative changes in the elastic fibers of the dermis (Pearse AD, Gaskell SA, Marks R. J Invest Dermatol 1987; 88 83-87; Berton TR, Mitchell DL, Fischer SM, Looniskar MF J Invest Dermatol 1997; 109: 340-347). Further, Chronic UVB exposure is a risk factor for the appearance of benign lesions, such as seborrheic keratoses, and premalignant, such as actinic keratosis (Kripke ML. Cancer Res 1994; 54: 6102-6105). Currently does not exist effective treatment for skin aging (Dermatol Surg. Special Issue: Cosmeceuticals. Guest editors: Draelos ZD, Brody HJ. 2005).

On the other hand, the hair follicle constitutes the functional unit for hair elongation. Hirsutism is a clinical picture of excessive hair growth with type pattern androgenic (face, thorax, areolas, alba line, bottom of the back, buttocks, extremities and external genitalia), secondary to an increase in androgenic activity. Hypertrichosis is a picture of excessive hair growth in sensitive areas and not androgen sensitive.

The prevention and / or treatment of obesity it is a very important factor in reducing morbidity and mortality associated with cardiovascular diseases and type 2 diabetes that represent a very health and social cost high in industrialized countries. There is currently no Effective medical treatment for obesity. Effective therapies for the treatment of obesity should interfere in the adipose tissue growth. To increase tissue mass adipose is essential that preadipocytes differ in a phenotype of mature adipocytes. The differentiation process of preadipocyte in adipocyte, in addition to morphological changes, it accompanies metabolic processes such as the ability to store energy in the form of triglycerides (McDougald OA, Lane MD. Annu Rev Biochem, 1995, 64: 345-373; Spiegelman BM, Flier JS. Cell 1996, 87: 377-389). Therefore, the pharmacological inhibition of preadipocyte differentiation in adipocytes constitutes a therapeutic strategy to treat the obesity.

There is a need to find treatment alternatives to current photo aging treatments cutaneous, hirsutism or obesity, both from the point of aesthetic and therapeutic view, based on the use of active principles.

Description of the invention Description of the figures

Figure 1. Appearance of skin aged before of treatment (A) and after topical treatment for 3 months (check) with a cream containing the acid 2,5-dihydroxybenzene sulfonic acid (B). The arrows mark the same area of actinic lentigo before and after treatment.

Figure 2. Topical treatment with the cream previously described (twice a day for 11 days) of the Human skin (basal conditions shown in Figure 2A) produces a decrease in seborrheic keratosis (large circle) as well as of viral warts (small circle), as shown by the figure 2B.

Figure 3. Appearance of the skin before treatment (A) and after topical treatment for 2 months with a cream containing the acid 2,5-dihydroxybenzene sulfonic acid (B). In image A more hairiness is observed than in image B.

Figure 4. Photo A corresponds to a crop control where most cells are adipocytes containing triglyceride deposits Photo B shows a treated crop with 2,5-dihydroxybenzene sulfonic acid. These cells, in a large proportion, have an undifferentiated appearance (preadipocytes) with low accumulation of triglycerides in the cytoplasm.

Figure 5. Represents a histogram that corresponds to the quantification of triglycerides (detected cytometrically due to the absorbance of Oil Red O) in three crops controls and three cultures treated with acid 2,5-dihydroxybenzene sulfonic. Ordered: absorbance at 510 nm. Controls histogram (white); Histogram with treatment (dark); * * * p <0.001.

Figure 6. Reversal of solar lentigines after treatment for two weeks with cream dobesilate. A, before treatment. B, after treatment.

Figure 7. Acid inhibition gentysic of pre-adipocyte differentiation and adipogenesis On the Y axis the% of absorbance at 510 nm, the left column being the control (without treatment) and the right column the result of Gentisic acid treatment.

Figure 8. Acid inhibition gentysic of pre-adipocyte differentiation and adipogenesis The photo on the left is the control and the right it is the result of treatment with gentisic acid for two weeks

Detailed description of the invention

Derivatives 2,5-dihydroxybenzene of the invention or any of its pharmaceutically acceptable salts are those that are represented by formula I comprising Dobesilate, Homodobesilate, Dobesilate esters and their salts pharmaceutically acceptable for the treatment of obesity (excessive adipogenesis), hirsutism, hypertrichosis, al wrinkles skin, photo-aging, photoprotection, atopic dermatitis, contact dermatitis, viral warts, the actinic keratosis, seborrheic keratosis, pigmentation Cutaneous and / or cutaneous hyperpigmentation.

In particular, the present invention it comprises 2,5-dihydroxybenzene derivatives of the invention or any of its pharmaceutically acceptable salts represented by the formula (I) comprising the gentisic acid, homogentisic acid, esters of gentisic acid, esters of acid homogetic and its pharmaceutically acceptable salts for treatment of obesity (excessive adipogenesis), hirsutism and viral warts

Derivatives 2,5-dihydroxybenzene of the invention can be use, optional and, in conjunction with at least one of the following therapeutic agents: immunomodulators, corticosteroids, immunosuppressants, emollients, barrier creams, moisturizing agents, corticosteroids, local anesthetics, anti-histamines, resin Podofilino Cantharín, ac. salicylic, imiquimod, bleomycin, exfoliating agents (alpha hydroxy acids, trichloroacetic acid, phenols) or diclofenac gel, 5-fluoracil, photo-protectants, bleaching, anti-oxidants, anti-inflammatory Non steroids and the like. Another aspect of the invention is that 2,5-dihydroxybenzene derivatives can be use, optionally, combining with each other. This way and as an example they could be combined in equal proportions or different, dobesilate with the homogetic, or the gentysic with the homogentysic, or a dobesilate ester with the homogentisic and Similar. Such combinations may be in the same formulation or in formulations that would be used sequentially

Below are definitions of terms and chemical groups that are part of the formulas:

"Alkyl" refers to an alkyl group substituted or unsubstituted, acyclic, straight or branched chain comprising from one to about fourteen atoms of carbon (preferably from one to about eight atoms carbons). Examples of lower alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, pentyl, neopentyl, iso-amyl, hexyl, octyl, and the like.

"Substituted alkyl" refers to a group alkyl in which one or more of the hydrogen atoms have been replaced by one or more R 100 groups, in which each R 100 is independently a hydroxy, an ester, an amidyl, a oxo, a carboxyl, a carboxamide, a halo, a cyano, a nitrate, a nitrite, a thionitrate, a thionitrite or an amino group.

"Aryl" refers to an aromatic ring monocyclic Examples of aryl groups include phenyl, benzyl, pyridyl, furanyl and the like. Aryl groups can be substituted with one, two or three substituents selected independently of lower alkyl, alkoxy, alkylthio, amino, alkylamino, dialkyloamino, arylamino, diarylamino, alkylarylamino, halo, cyano, alkylsulfinyl, hydroxy, carboxy, carboxylic ester, dicarboxylic acid, alkylcarboxylic ester, aryl, arylcarboxylic acid, arylcarboxylic ester, alkylcarbonyl, arylcarbonyl, amidyl, ester, carboxamido, alkylcarboxamido, carbomyl, sulfonic acid, sulfonic ester, sulfonamido and nitro. Examples of substituted aryl groups include tetrafluorophenyl, pentafluorophenyl, sulfonamide, alkylsulfonyl, arylsulfonyl and the like.

"Arylalkyl" refers to an aryl radical attached to an alkyl radical. Examples of arylalkyl groups include benzyl, phenylethyl, 4-hydroxybenzyl, 3-fluorobenzyl, 2-fluorophenylethyl, and  Similar.

"Alkyloaryl" refers to a group alkyl to which an aryl group is added. Examples of the groups Alkylaryl include benzyl, phenylethyl, hydroxybenzyl, fluorobenzyl, fluorophenylethyl, and the like.

"Alkylsulfoniol" refers to R 50 -S (O) 2 -, in which R 50 is a lower alkyl group.

"Arylsulfonyl" refers to R 55 -S (O) 2 -, in which R 55 is an aryl group.

"Alkylcarbonyl" refers to R_ {52} -C (O) -, in which R_ {52} is a alkyl group.

"Arylcarbonyl" refers to R_ {55} -C (O) -, in which R_ {55} is a aryl group.

"Amino" refers to an organic compound any one that contains at least one basic nitrogen atom.

"Organic cation" refers to an ion Metallic with positive charge. Examples of organic cations include substituted or unsubstituted alkyl, ammonium cations, primary, secondary or tertiary terms, alkyls, aminos aryls, cyclic aminos, N, N'-dibenzylethylenediamino and the like.

"Inorganic cation" refers to an ion Metallic with positive charge. Examples of inorganic cations include Group I metal cations, such as, for example, sodium potassium, magnesium, calcium, and the like.

The term "patient" as expressed in the present invention it refers to animals, preferably mammals, more preferably humans, and includes men and women, and children and adults.

The expression "effective amount" as expressed in the present invention refers to the amount of compound and / or composition that is effective to achieve its purpose wanted.

The terms "treat" or "treatment" as expressed in the present invention they refer to the use of the compounds or compositions of the present invention so prophylactic to avoid the symptoms of the disease or disorder, or therapeutically to improve an existing condition.

The term "topic" as expressed in the present invention it refers to the supply of a compound by application to the body surface and includes, but without limitation, transdermal supply and supply through the mucous membrane.

The term "transdermal" as it is express in the present invention refers to the supply of a compound that passes through the skin and into the torrent blood

The expression "through the mucosa" as and as expressed in the present invention refers to the supply of a compound that passes through the mucous tissue and into of the bloodstream.

The term "parenteral" as it is express in the present invention refers to the supply of a composed of subcutaneous, intravenous, intramuscular injection, intracardiac, intradermal, intraperitoneal, intrathecal or intrasternal and also includes local infusion techniques or systemic

The expression "empowerment of the penetration "or" enhancement of permeation "as expressed in the present invention refer to an increase in the permeability of the skin or mucous tissue to a compound pharmacologically active selected so that it increases the speed at which the compound penetrates through the skin or tissue  mucous.

The "excipients" or "vehicles" as and as expressed in the present invention refer to materials suitable for the administration of a compound e include any of said materials known in the art such as, for example, any liquid, gel, solvent, liquid diluent, solubilizer or the like, which is non-toxic and that does not interact with any component of the composition of a harmful mode.

The expression "sustained release" as and as expressed in the present invention refers to the release of an active compound and / or composition so that the levels in Blood of the active compound is maintained in a therapeutic range desirable over a period of time. Release formulation Sustained can be prepared using any conventional method known to a specialist in the art to obtain the desired release characteristics.

The term "atopic dermatitis" as expressed in the present invention refers to a disease Chronic that affects the skin. Atopic dermatitis is due to a combination of genetic factors and environmental

The term "contact dermatitis" as and as expressed in the present invention it refers to injuries that they occur on the skin when it comes in contact with a antigen or an irritant.

The term "viral warts" as it is express in the present invention refers to benign growths of the skin or mucous membranes.

The term "actinic keratosis" as Expressed in the present invention refers to dry lesions, scaly scratchy texture that forms on the outer layer of the skin after exposure to ultraviolet light for years, such as the solar.

The term "Seborrheic keratosis" as and as expressed in the present invention it refers to growths Non-cancerous outer skin layer.

The term "therapeutic agent" as expressed in the present invention refers to, and includes, but It is not limited to immunomodulatory treatments, such as tacrolimus ointment or pimecrolimus cream, and the like; both topical corticosteroids (in creams, ointments, ointments, or gels) as systemic; topical immuno-suppressants or systemic, such as cyclosporine, metrotrexate, azathioprine, and the like; phototherapy; emollients, as per example, white petrolatum, eucerin, urea cream, oil mineral, aluminum acetate, and the like; barrier creams, such as rust paste zinc, and the like; moisturizing agents, such as menthol, camphor, and the like; local anesthetics, such as lidocaine, and the like; topical corticosteroids, such as triamcinolone acetate, and the like; systemic corticosteroids, such as for example, prednisone, and the like; anti-histamines, such as diphenhydramine, hydroxyzine, and the like; podophyllin resin in local application; cantharín, alone or in combination with podophyllin; ac. salicylic in local application; imiquimod; bleomycin; exfoliating agents, such as for example, alpha hydroxy acids (glycolic acid, acid salicylic, lactic acid), trichloroacetic acid, phenols (acid Carbolic, croton oil, and the like; diclofenac gel; 5-fluoracil, bleaching agents and photo-protectors and the like. A therapeutic agent includes pharmaceutically acceptable salts thereof, pro-drugs and pharmaceutical derivatives of same

In one embodiment, the invention describes the methods of using the compound of Formula (I), and salts Pharmaceutically acceptable thereof:

where the compound of Formula (I) is:

one

in the which:

R 1 in each case is selected so independently between -OH or -OR2;

Y is -SO3H, -SO3 {-}. X +, -SO 3 R 3, -PO 3 H, -PO 3 - - X +, -PO 3 R 3, -CO 2 H, -CO 2 - X + or -CO 2 R 3;

X + is an organic or inorganic cation;

R2 is a low alkyl group, a group aryl, an arylalkyl group, an alkylsulfonyl group, a group arylsulfonyl, a group alkylarylsulfonyl, a group arylalquisulfonyl, an aryloxyalkyl group, a group alkylcarbonyl or an arylcarbonyl group;

R 3 is a low alkyl group, a group aryl, an arylalkyl group or an alkylaryl group; a is a number integer between 0 and 6;

The X + cation in the compound of formula I it can be any physiologically acceptable cation known in the state of the art, which includes but is not limited to described in P. Heinrich Stahl, Camille G. Wermuth (Editiors), "Handbook of Pharmaceutical Salts Properties, Selections and Use ", Verlag Helvetica Chimica Acta, Zurich, Switzerland, Wiley-VCH, Weinheim, Germany, 2002.

The cation X is selected so that the general load of formula I is neutral.

In another aspect of the invention, R2 is selected from acetyl (-C (O) CH 3), tosyl (-SO_ {2} -C_ {6} H4 {CH3}) p or p-chlorophenoxy isobutyryl (-C (O) -C (CH 3) 2 -O-C 6 H 4 Cl).

In another aspect of the invention, R 3 is selected from methyl, ethyl, isopropyl or C 6 H 5 -.

In another aspect of the invention the cation Inorganic is sodium, potassium, lithium, calcium or magnesium.

In another aspect of the invention the cation organic is [NH_ {4-p} R_ {p}] +: where p is an integer between 0 and 4 and R is a low alkyl group.

In another aspect of the invention, the cation organic is the diethylamine group [H 2 N + (C 2 H 5) 2], piperazine or pyridine

In another aspect of the invention the compound of formula I its pharmaceutically acceptable salts are:

2

4

where:

n is an integer between 1 and 2;

m is an integer between 1 and 2; Y

X, R2 and R3 as defined in The present invention.

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In another aspect of the invention the compound of formula I is:

2,5-dihydroxybenzene acid sulfonic acid (Dobesilate), and the group can be substituted -SO_ {3} - by - (CH 2) a-SO 3 {-}, this being Homodobesilate compound, or the group can be substituted -SO_ {3} for -PO_ {3} or for - (CH 2) a-PO 3 -;

Calcium 2,5-dihydroxybenzenesulfonate (Dobesilate calcic);

Potassium 2,5-dihydroxybenzenesulfonate (Dobesilate potassium);

Magnesium 2,5-dihydroxybenzenesulfonate (Dobesilate magnesium);

Diethylamine 2,5-dihydroxybenzenesulfonate (Etamsilate);

Acid 5-hydroxy-2 - {[(4-methylphenyl) sulfonyl] oxy} benzene sulfonic;

Acid 2-hydroxy-5 - {[(4-methylphenyl) sulfonyl] oxy} benzene sulfonic;

Acid 2,5-bis {[(4-methylphenyl) sulfonyl] oxy} benzene sulfonic;

Acid 2- (acetyloxy) -5-hydroxybenzene sulfonic;

Acid 5- (acetyloxy) -2-hydroxybenzene sulfonic;

Acid 2,5-bis (acetyloxy) benzene sulfonic;

Acid 2- (benzyloxy) -5-hydroxybenzene sulfonic;

Acid 5- (benzyloxy) -2-hydroxybenzene sulfonic;

Acid 2,5-bis (benzyloxy) benzene sulfonic;

Acid 2- (acetyloxy) -5-hydroxybenzoic;

Acid 2-hydroxy-5- (acetyloxy) benzoic;

Acid 2,5-bis (acetyloxy) benzoic;

Acid [2- (acetyloxy) -5-hydroxyphenyl] acetic acid;

Acid [5- (acetyloxy) 2-hydroxyphenyl] acetic acid;

Acid [2,5-bis (acetyloxy) phenyl] acetic acid;

2,5-dihydroxybenzoic acid (gentisic acid);

2,5-dihydroxyphenyl acetic acid (homogentisic acid); and its pharmaceutically acceptable salts.

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The compounds of the invention that have one or more asymmetric carbon atoms can exist as enantiomers optically pure, pure diastereomers, mixtures of enantiomers, mixtures of diastereomers, racemic mixtures of enantiomers, diastereomeric racemates or mixtures of diastereomeric racemates. It should be understood that the invention provides and includes in its scope all these isomers and mixtures thereof.

The compounds of Formula (I) can also be in the form of solvates, particularly in the form of hydrates. The preparation of the compounds of Formula (I) as well as their solvates can be performed by a person skilled in the art using conventional methods and reagents available in the market.

The compounds of the invention are formulated in form of potassium, calcium, magnesium and ethylamine salts. He ethamsylate (ethylamine dobesilate), is a commercial product known. Within the scope of this invention is any pharmaceutically acceptable salt of the compound. The term "pharmaceutically acceptable salts" includes salts metallic or addition salts that can be used in Pharmaceutical forms. The pharmaceutically acceptable salts of Compounds of the invention can be obtained from acids or organic or inorganic bases by conventional methods making react the appropriate acid or base with the compound.

Pharmaceutical compositions containing the formulas of the invention can be presented in any form of administration deemed appropriate, for example, via systemic, oral, parenteral or topical, for which they will include pharmaceutically acceptable excipients necessary for the formulation of the desired administration form.

Thus, in a preferred aspect of the present invention refers to its use in the treatment of hirsutism and hypertrichosis, obesity or adipogenesis excessive, and treatment of viral warts in a patient in need of this and that covered the administration to the patient of an effective amount of the compounds and / or compositions of the formula (I) described. The compounds of the formula (I) can be administer, optionally, in conjunction with at least one agent therapeutic, such as immunomodulatory treatments, corticosteroids, immunosuppressants, phototherapy, emollients, barrier creams, moisturizing agents, local anesthetics, anti-histamines, resin Podofilino Cantharín, ac. salicylic, imiquimod cream, bleomycin, bleaches, photo-protectors and Similar.

Thus, one aspect of the present invention is refers to its use for the treatment of pathologies associated with skin photoaging, atopic dermatitis, a contact dermatitis as well as and its therapeutic use in wrinkles on the skin, in actinic keratosis, in seborrheic keratosis, in skin pigmentation and / or in skin hyperpigmentation, in a patient in need of this and that covers administering to patient an effective amount of the compounds and / or of the Compositions of the formula (I) described, provided that:

And it must be SO 3 H, -SO 3 {-}. X +, -SO 3 R 3, -PO 3 H, -PO 3 - - X + or -PO_ {3} R_ {3}.

In this method the compounds of the formula (I) are can optionally administer in conjunction with at least a therapeutic agent, for example with treatments immunomodulators, corticosteroids, phototherapy, emollients, barrier creams, moisturizing agents, anesthetics local, anti-histamines, podophyllin resin, Cantharín, salicylic acid, imiquimod cream, bleomycin, bleaching agents, photoprotectors, anti-oxidants, anti-inflammatory Non steroids and the like.

Another aspect of the invention is that 2,5-dihydroxybenzene derivatives of the formula I They can be used, optionally, by combining with each other. From this form and as an example could be combined in proportions same or different, the dobesilate with the homogentisico, or the gentysic with the homogetic, or a dobesilate ester with the homogetic and similar. Such combinations may be in the same formulation or in formulations that would be used sequentially

On the other hand the application of the compounds 2,5-dihydroxybenzene represented by the formula I can be performed independently or, in one aspect preferred, together using equivalent proportions or other than other compounds 2,5-dihydroxybenzene represented by the formula I (including pharmaceutically acceptable salts and esters) and said compounds may be in the same formulation or in independent formulations that would be administered in a way sequential or simultaneous.

Another aspect of the invention is that 2,5-dihydroxybenzene derivatives of the formula I They can be used, optionally, by combining with each other. From this form and as an example could be combined in proportions same or different, the dobesilate with the homogentisico, or the gentysic with the homogetic, or a dobesilate ester with the homogetic and similar. Such combinations may be in the same formulation or in formulations that would be used sequentially or simultaneously.

Thus, in a first aspect the present invention refers to a cosmetic product that comprises derivatives 2,5-dihydroxybenzenes or any of its salts Pharmaceutically acceptable represented by formula I.

In one embodiment the present invention is refers to a cosmetic product comprising derivatives 2,5-dihydroxybenzenes or any of its salts Pharmaceutically acceptable represented by formula I characterized in that the compound of formula I is acid 2,5-dihydroxybenzene sulfonic acid (Dobesilate) or its pharmaceutically acceptable salts or esters.

In another embodiment the present invention is refers to a cosmetic product comprising derivatives 2,5-dihydroxybenzenes or any of its salts Pharmaceutically acceptable represented by formula I characterized in that the compound of formula I is acid 2,5-dihydroxybenzoic acid (gentisic acid) or its salts or pharmaceutically acceptable esters.

In another embodiment the present invention is refers to a cosmetic product comprising derivatives 2,5-dihydroxybenzenes or any of its salts Pharmaceutically acceptable represented by formula I characterized in that the compound of formula I is acid 2,5-dihydroxyphenyl acetic acid (homogentisic acid) or its pharmaceutically acceptable salts or esters.

In another embodiment the present invention is refers to a cosmetic product characterized in that the compound of formula I is 2,5-dihydroxybenzene acid sulfonic acid (Dobesilate) or its salts or esters pharmaceutically acceptable characterized by consisting of a formulation anti-photoaging or photoprotective of the skin.

In another embodiment the present invention is refers to a cosmetic product characterized in that the compound of formula I is 2,5-dihydroxybenzene acid sulfonic acid (Dobesilate) or its salts or esters pharmaceutically acceptable characterized by consisting of a formulation for clarification of skin pigmentation.

In another embodiment the present invention is refers to a cosmetic product characterized in that the compound of formula I is 2,5-dihydroxybenzene acid sulfonic acid (Dobesilate) or its salts or esters pharmaceutically acceptable characterized by consisting of a formulation for clarification of skin hyperpigmentation.

In another embodiment the present invention is refers to a cosmetic product characterized in that the compound of formula I is 2,5-dihydroxybenzene acid sulfonic acid (Dobesilate) or its salts or esters pharmaceutically acceptable characterized by consisting of a formulation for the treatment of hirsutism and / or hypertrichosis.

In another embodiment the present invention is refers to a cosmetic product characterized in that the compound of formula I is 2,5-dihydroxybenzene acid sulfonic acid (Dobesilate) or its salts or esters pharmaceutically acceptable characterized by consisting of a formulation for the treatment of viral warts, actinic keratosis and / or seborrheic keratosis.

In another embodiment the present invention is refers to a cosmetic product characterized in that the compound of formula I is 2,5-dihydroxybenzene acid sulfonic acid (Dobesilate) or its salts or esters pharmaceutically acceptable characterized by consisting of a formulation for the treatment of atopic dermatitis and / or dermatitis of Contact.

In another embodiment the present invention is refers to a cosmetic product characterized in that the compound of formula I is 2,5-dihydroxybenzene acid sulfonic acid (Dobesilate) or its salts or esters pharmaceutically acceptable characterized by consisting of a formulation for the aesthetic treatment of obesity.

In another embodiment the present invention is refers to a cosmetic product characterized in that the compound of formula I is 2,5-dihydroxybenzene acid sulfonic acid (Dobesilate) or its salts or esters pharmaceutically acceptable characterized by consisting of a formulation for Therapeutic use of wrinkles on the skin.

In another embodiment the present invention is refers to a cosmetic product characterized in that the compound of formula I is gentisic acid or homogentisic acid or its salts or esters characterized by consisting of a formulation for the aesthetic treatment of obesity or excessive adipogenesis, to the treatment of hirsutism and hypertrichosis, and treatment of viral warts.

In another embodiment the present invention is refers to a cosmetic product according to any of the aspects previous characterized by presenting in the form of cream, ointment, Ointment, microsomes, patches dressings.

In another embodiment the present invention is refers to a cosmetic product according to any of the aspects previous characterized by containing 5% salt concentration Potassium of 2,5 dihydroxybenzene sulfonic acid.

In another embodiment the present invention is refers to a cosmetic product according to any of the aspects previous characterized by understanding as excipients: alcohol cetyl (2.5%), stearyl alcohol (2.5%), liquid petrolatum (30%), Filament petrolatum (20%), oleate sorbonate (5%) and distilled water (c.s.p 100 gr).

In another embodiment the present invention is refers to the use of 2,5-dihydroxybenzene derivatives or any of its pharmaceutically acceptable esters or salts represented by formula I for the preparation of a formulation intended for use in cosmetics.

In one embodiment the present invention is refers to the use of 2,5-dihydroxybenzene derivatives or any of its pharmaceutically acceptable esters or salts represented by formula I where the compound of formula I is the 2,5-dihydroxybenzene sulfonic acid (Dobesilate) or its salts or esters for the preparation of a drug or medication intended for cosmetic or therapeutic treatment of wrinkles in the skin, skin photoaging, skin pigmentation, of skin hyperpigmentation, hirsutism, hypertrichosis, of actinic keratosis, of keratosis seborrheic viral warts, atopic dermatitis, contact dermatitis or obesity (excessive adipogenesis).

In one embodiment the present invention is refers to the use of 2,5-dihydroxybenzene derivatives or any of its pharmaceutically acceptable esters or salts represented by formula I where the compound of formula I is the gentysic acid or its salts or esters for the preparation of a drug or medication intended for cosmetic treatment or treatment of obesity or excessive adipogenesis, for treatment of hirsutism and hypertrichosis, and treatment of viral warts

In another embodiment the present invention is refers to the use of 2,5-dihydroxybenzene derivatives or any of its pharmaceutically acceptable esters or salts represented by formula I where the compound of formula I is the 2,5-dihydroxyphenyl acetic acid (acid homogentisico) or its salts or esters for the preparation of a drug or medication intended for cosmetic treatment or Therapeutic obesity obesity or excessive adipogenesis, for the treatment of hirsutism and hypertrichosis, and treatment of viral warts.

In another embodiment the present invention is refers to a method of cosmetic treatment of any of the indications included in the following group: skin wrinkles, hirsutism, hypertrichosis, viral warts, or obesity consisting in administering to a patient a composition comprising the formula I.

In one embodiment the present invention is refers to a method of cosmetic treatment of any of the indications included in the following group: skin wrinkles, skin photoaging, skin pigmentation, skin hyperpigmentation, hirsutism, hypertrichosis, warts viral, actinic keratosis, seborrheic keratosis dermatitis atopic, contact dermatitis or obesity where the compound of formula I is 2,5-dihydroxybenzene sulfonic (Dobesilate) or its salts or esters.

In another embodiment the present invention is refers to a method of cosmetic treatment of obesity or excessive adipogenesis, for the treatment of hirsutism and hypertrichosis, and treatment of viral warts where the compound of formula I is the acid 2,5-dihydroxybenzoic acid (gentisic acid) or its salts or esters.

In another embodiment the present invention is refers to a method of cosmetic treatment of obesity or excessive adipogenesis, for the treatment of hirsutism and hypertrichosis, and treatment of viral warts where the compound of formula I is the acid 2,5-dihydroxyphenyl acetic acid (homogentisic acid) or its salts or esters.

In another embodiment the present invention is refers to a method of therapeutic treatment of any of the indications included in the following group: skin wrinkles, hirsutism, hypertrichosis, viral warts, or obesity consisting in administering to a patient a composition comprising the formula I.

In one embodiment the present invention is refers method of therapeutic treatment of any of the indications included in the following group: skin wrinkles, skin photoaging, skin pigmentation, skin hyperpigmentation, actinic keratosis, keratosis seborrheic, atopic dermatitis, contact dermatitis where the compound of formula I with the condition that Y must be: SO 3 H, -SO 3 {-}. X +, -SO 3 R 3, -PO 3 H, -PO_ {3} - X + or -PO 3 R 3.

Thus, in a first aspect the present invention refers to the use of 2.5 dihydroxybenzene derivatives, their esters or pharmaceutically acceptable salts represented by formula I for the preparation of a drug, medication or composition intended for cosmetic treatment of any of the following diseases: obesity or excessive adipogenesis, viral warts, hypertrichosis or hirsutism.

In a second aspect the present invention is refers to the use of 2.5 dihydroxybenzene derivatives, represented by formula I where the compound of formula I is 2.5 dihydroxybenzene sulfonic acid (Dobesilate) or its esters or salts pharmaceutically acceptable for the preparation of a drug, medicament or composition intended for cosmetic treatment of any of the following diseases: skin wrinkles, skin photoaging, skin pigmentation, hyperpigmentation cutaneous, actinic keratosis, seborrheic keratosis, dermatitis atopic, contact dermatitis or solar lentigines.

In a third aspect the present invention is refers to the use of 2.5 dihydroxybenzene derivatives, represented by the formula I where the substituent Y of said formula is SO 3 H, -SO 3 {-}. X +, -SO 3 R 3, -PO 3 H, -PO_ {3} - X + or -PO_ {R3} for the elaboration of a drug, medication or composition intended for treatment Cosmetic or medical of any of the following diseases: skin wrinkles, skin photoaging, skin pigmentation, skin hyperpigmentation, actinic keratosis, keratosis seborrheic, atopic dermatitis, contact dermatitis or lentigines solar.

A fourth aspect of the present invention is refers to a method of cosmetic treatment of any of the diseases included in the following group: obesity or excessive adipogenesis, viral warts, hypertrichosis or hirsutism which consists of administering to a patient a composition that understand formula I or its pharmaceutically acceptable salts or esters acceptable.

A fifth aspect of the present invention is refers to a method of cosmetic treatment of any of the diseases included in the following group: skin wrinkles, skin photoaging, skin pigmentation, hyperpigmentation cutaneous, actinic keratosis, seborrheic keratosis, dermatitis atopic, contact dermatitis or solar lentigines consisting of administer to a patient a composition that includes the formula I where the compound of formula I is 2.5 dihydroxybenzene sulfonic acid (Dobesilate) or its salts or esters pharmaceutically acceptable.

A sixth aspect of the present invention is refers to a method of cosmetic treatment of any of the diseases included in the following group: skin wrinkles, skin photoaging, skin pigmentation, hyperpigmentation cutaneous, actinic keratosis, seborrheic keratosis, dermatitis atopic, contact dermatitis or solar lentigines consisting of administer to a patient a composition that includes the formula I where the substituent Y of said formula is SO 3 H, -SO 3 {-}. X +, -SO 3 R 3, -PO 3 H, -PO 3 {-}. X + or -PO 3 R 3 or its salts or esters pharmaceutically acceptable.

A seventh aspect of the present invention is refers to a method of therapeutic treatment of any of the diseases included in the following group: obesity or excessive adipogenesis, viral warts, hypertrichosis or hirsutism which consists of administering to a patient a composition that understand formula I or its pharmaceutically acceptable salts or esters acceptable.

An eighth aspect of the present invention is refers to a method of therapeutic treatment of any of the diseases included in the following group: skin wrinkles, skin photoaging, skin pigmentation, hyperpigmentation cutaneous, actinic keratosis, seborrheic keratosis, dermatitis atopic, contact dermatitis or solar lentigines consisting of administer to a patient a composition that includes the formula I where the compound of formula I is 2.5 dihydroxybenzene sulfonic acid (Dobesilate) or its salts or esters pharmaceutically acceptable.

A ninth aspect of the present invention is refers to a method of therapeutic treatment of any of the diseases included in the following group: skin wrinkles, skin photoaging, skin pigmentation, hyperpigmentation cutaneous, actinic keratosis, seborrheic keratosis, dermatitis atopic, contact dermatitis or solar lentigines consisting of administer to a patient a composition that includes the formula I where the substituent Y of said formula is SO 3 H, -SO 3 {-}. X +, -SO 3 R 3, -PO 3 H, -PO 3 {-}. X + or -PO 3 R 3 or its salts or esters pharmaceutically acceptable.

In one aspect of the invention, the compounds 2,5-dihydroxybenzenes of the formula (I) can be topically administered in a formulation that covers an amount Approximately 0.001% to approximately 30% (pip) of the 2,5-dihydroxybenzene compounds of the formula (I). In a preferred aspect of the invention, the compounds 2,5-dihydroxybenzenes of the formula (I) can be topically administered in a formulation that covers an amount from about 0.01% to about 20% (pip) of the 2,5-dihydroxybenzene compounds of the formula (I). In another preferred aspect of the invention, the compounds 2,5-dihydroxybenzenes of the formula (I) can be topically administered in a formulation that covers an amount from about 0.1% to about 15% (pip) of the 2,5-dihydroxybenzene compounds of the formula (I). In a preferred aspect of the invention, the compounds 2,5-dihydroxybenzenes of the formula (I) can be topically administered in a formulation that covers an amount from about 0.5% to about 10% (pip) of the 2,5-dihydroxybenzene compounds of the formula (I). In another preferred aspect of the invention, the compounds 2,5-dihydroxybenzenes of the formula (I) can be topically administered in a formulation that covers an amount from about 1% to about 5% (pip) of the 2,5-dihydroxybenzene compounds of the formula (I). In another preferred aspect of the invention, derivatives 2,5-dihydroxybenzenes of the formula (I), are can be administered topically in a formulation that encompasses a amount from about 2.5% to about 4% (w / w) of the 2,5-dihydroxybenzene compounds of the formula (I). The topical formulation of the compounds covered in the 2,5-dihydroxybenzenes of the formula (I) are You can administer as a single dose once a day; or in multiple doses several times throughout the day. In one aspect Preferred of the invention is the topical formulation covering 30%, 20%, 15%. 10%, 5%, 2.5%, 1%, 0.5%, 0.1% or 0.001% of the 2,5-dihydroxybenzene compounds of the formula (I), it is administered four times a day. In another preferred aspect of the invention the topical formulation that encompasses approximately the 30%, 20%, 15%. 10%, 5%, 2.5%, 1%, 0.5%, 0.1% or 0.001% of the 2,5-dihydroxybenzene compounds of the formula (I) is administered three times a day. In another preferred aspect of the invention the topical formulation that encompasses approximately the 30%, 20%, 15%. 10%, 5%, 2.5%, 1%, 0.5%, 0.1% or 0.001% of the 2,5-dihydroxybenzene compounds of the formula (I) is administered twice a day. In another preferred aspect of the invention the topical formulation covering approximately 30%, 20%, 15%. 10%, 5%, 2.5%, 1%, 0.5%, 0.1% or 0.001% of the 2,5-dihydroxybenzene compounds of the formula (I) It is given once a day.

Topical compositions

The product object of the invention is useful for topical applications on the skin. The compositions comprise an effective amount of the compounds of formula I, preferably between about 0.001 and 30%. The composition further comprises a pharmaceutically carrier acceptable. The appropriate vehicles remain in the place of application on the skin forming a continuous film that resists the Water immersion and perspiration. Generally, the vehicle is organic in nature and capable of containing the formulation of the invention dissolved or dispersed. Lotions, creams, solutions, gels and solids are usual physical forms of the composition.

Topical application means deposit or spread the compound and the compositions on the tissue epidermal (including oral skin and tissues, nasal gingival, etc.).

Lotions

Lotions comprise between approximately 0.001% and approximately 30% of the compounds of formula I, between 1% and 25% of an emollient and the appropriate amount of water. Examples of emollients are:

I.

Waxes and hydrocarbon oils. Like oil mineral, petrolatum, paraffin, ceresin, microcrystalline wax, polyethylene and perhydrosqualene.

II.

Silicone oils such as dimethyl polysiloxanes, methyl phenyl polysiloxanes and glycol-silicone co-polymers soluble in water and alcohol.

III.

Triglycerides, such as animal fats and oils and vegetables. Examples may be castor oil, liver oil of cod, corn oil, olive oil, almond oil, palm oil, sesame oil, cottonseed oil and soy.

IV.

Acetoglyceride esters, such as monoglycerides acetylated

V.

Ethoxylated glycerides, such as monostearate ethoxylated glycerol.

SAW.

Alkyl esters of fatty acids with 10 to 20 atoms carbon Methyl-, isopropyl and butyl esters of fatty acids are useful in this case. Examples can be hexyl laurate, isohexyl laurate, isohexyl palmitate, isopropyl palmitate, decacyl oleate, isodecacil oleate, hexadecacil stearate, decacil stearate, isopropyl isostearate, di-isopropyl adipate, di-isohexyl adipate di-hexyl, decacil-adipate, di-isopropyl sebacate, lauryl lactate, myristoyl lactate and cetyl lactate

VII.

Alkylene esters of fatty acids with 10 to 20 carbon atoms Examples that can be included are oleyl myristate, oleyl stearate and oleyl oleate

VIII.

Fatty acids with 10 to 20 carbon atoms. Be appropriate examples are pelargonic, lauric acids, myristic, palmitic, stearic, isostearic, hydroxystearic, linoleic, ricinoleic, arachidonic, behenic and oleic erect.

IX.

Fatty alcohols with 10 to 20 carbon atoms. Lauryl, myristoyl, palmitoyl, stearyl, isostearyl, hydroxiestearyl, oleyl, ricinoleil, behenyl, erucil and 2-octyl dodecanol alcohols are examples satisfactory fatty alcohols.

X.

Ethers of fatty alcohols. Fatty alcohols ethoxylates with 10 to 20 carbon atoms include lauryl, cetyl, Stearyl, isostearyl, oleyl and cholesterol alcohols having joined 1 to 50 groups of ethylene oxide or 1 to 50 groups of oxide propylene

XI

Ether esters as fatty acid esters of ethoxylated fatty alcohols.

XII.

Lanolin and derivatives. Lanolin, lanolin oil, lanolin wax, lanolin alcohols, lanolin fatty acids, isopropyl-lanolate, ethoxylated lanolin, alcohols of ethoxylated lanolin, ethoxylated cholesterol, lanolin alcohols propoxylated, acetylated lanolin, acetylated lanolin alcohols, lanolin-alcohol linoleates, ricinoleate lanolin-alcohols, ricinoleate acetate lanolin-alcohols, lanolin hydrogenolysis and liquid lanolin absorption bases or semi-solid are illustrative examples of emollients lanolin derivatives.

XIII

Polyhydric alcohols and polyether derivatives. Propylene glycol, di-propylene glycol, polypropylene glycol 2,000 and 4,000, poly-oxyethylene poly-propylene glycols, glycerol, ethoxylated glycerol, propoxylated glycerol, sorbitol, ethoxylated sorbitol, hydroxypropyl sorbitol, polyethylene glycol 200-6,000, methoxy-polyethylene glycols 350, 550, 750, 2,000, 5,000, poly (ethylene oxide) homopolymers (100,000-5,000,000), poly-alkylene glycols and derivatives, hexylene glycol (2-methyl-2,4-pentanediol), 1,3-butylene glycol, 1,2,6-hexanotriol, USP ethoexadiol (2-ethyl-1,3-hexanediol) and poly-oxypropropylene derivatives of trimethylol propane are possible examples.

XIV

Esters of polyhydric alcohols. Monkey di-acyl esters of ethylene glycol, mono- and di-acyl esters of diethylene glycol, mono- and di-acyl esters of polyethylene glycol (200-6,000), mono- and di-acyl esters of propylene glycol, polypropylene mono-oleate glycol 2,000, polypropylene glycol mono-stearate 2,000, ethoxylated propylene glycol mono-stearate, mono- and di-acyl esters of glycerol, poly-acyl esters of polyglycerol, ethoxylated glycerol mono-stearate, 1,3-Butylene Mono Stearate glycol, 1,3-butylene di stearate glycol, acyl ester of poly-oxyethylene polyol, acyl esters of sorbitan and acyl esters of poly-oxyethylene sorbitan are examples satisfactory

XV.

Waxes such as beeswax, spermaceti, miristoil Miristaro and Stearyl Stearate. XVI. Beeswax derivatives as beeswax from poly-oxyethylene sorbitol. These are products of the reaction of beeswax with ethoxylated sorbitol with variable ethylene oxide content, forming a mixture of ether esters.

XVII

Vegetable waxes including carnauba wax and candelilla

XVIII.

Phospholipids such as lecithin and its derivatives

XIX.

Sterols As examples, cholesterol and acyl esters of cholesterol

XX.

Amides such as acyl amides, ethoxylated acyl amides and solid fatty acid alkanolamides.

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The lotions of the invention in addition they would comprise between 1% and 30% of an emulsifier. The emulsifiers would be anionic, cationic or non-ionic Examples among Non-ionic are fatty alcohols between 10 and 20 carbon atoms, 10-20 fatty alcohols carbons condensed with 2 to 20 moles of ethylene oxide or oxide of propylene, alkyl phenols with 6 to 12 carbons in the chain alkyl condensed with 2 to 20 moles of ethylene oxide, mono- and di-acyl esters of ethylene glycol, where the acid Fat contains 10 to 20 carbons, monoglycerides where the acid Fat contains 10 to 20 carbons, diethylene glycol, polyethylene glycols of molecular weight between 200 and 6,000, polypropylene glycol of molecular weight between 200 and 3,000, glycerol, sorbitol, sorbitan, polyoxyethylene sorbitol, polyoxyethylene sorbitan and wax esters hydrophilic Suitable anionic emulsifiers would be fatty acids  saponified (soaps) with potassium, sodium or triethanolamine, where The fatty acid contains 10 to 20 carbons. Other emulsifiers Suitable anionics would include alkali metals, ammonium sulfate or ammonium sulfate with alkyl substitutions, alkyl aryl sulphonates and ethoxy ether sulfonates alkyl with 10 to 30 carbons in the alkyl chain and 1 to 50 ethylene oxide units. Cationic emulsifiers satisfactory would include quaternary ammoniums and compounds of morpholinium and pyridinium.

Some described emollients also have emulsifying capacities. When a lotion includes any of these emollients, the addition of an emulsifier would not be necessary, although it could be included in the formulation.

The composition is completed with water. The Lotions are formulated simply by mixing all the components together. Preferably, the compounds of formula I are dissolve in the emollient and the mixture is added to the water. Components Optional as emulsifier or common additives can be included In the composition. A common additive is a thickening agent constituting from 1% to 30% of the composition. Examples of agents Suitable thickeners are: crosslinked carboxy polymers polymethylene, methyl cellulose, polyethylene glycols, gums and bentonite.

Creams

The compositions of the present invention They can also be formulated in cream form. Creams contain from 0.001% to 30% of the compounds of formula I, from 5% to 50% of an emollient and the right amount of water. Emollients previously described are also suitable for the formulation of the cream. Optionally, the cream may contain an emulsifier in a proportion of between 3% and 50%. The emulsifiers described previously they would also be suitable in this case.

Solutions

The compositions of the invention can also be formulated as a solution. The solutions contain 0.001% to 30% of the compounds of formula I, and the appropriate amount of an organic solvent. Organic substances capable of acting  As solvents or being part of the solvent system are: propylene glycol, polyethylene glycol (200-600), polypropylene glycol (425-2025), glycerin, sorbitol esters, 1,2,6-hexanotriol, ethanol, isopropanol, diethyl tartrate, butanediol and mixtures thereof. The systems Solvents may also contain water.

These compositions are applied to the skin in solution form, or the solutions are formulated in aerosol form and applied to the skin as a spray. The compositions in spray form additionally contain between 25% and 80% of A suitable propellant. Examples of propellants are: hydrocarbons gold, fluorinated and fluorochlorinated low molecular weight. Oxide nitrous and carbon dioxide are also used as gases propellant They are used in sufficient quantity to expel the cartridge contents.

Gels

The gel-shaped composition could be obtained simply by adding a suitable thickening agent to the solution composition described above. The suitable thickening agents have been described in the chapter referring to lotions. Gel formulations contain approximately 0.001% to 30% of the compounds of formula I, 5% to 75% of an appropriate organic solvent, 0.5% to 20% of an agent adequate thickener and the required amount of water.

Solids

The compositions of the present invention They can also be formulated as a solid. Such forms They have a bar format designed for application on the lips  or other parts of the body. These compositions contain approximately 0.001% to 30% of the compounds of formula I, and from 50% to 98% of an emollient as described previously. The composition may additionally contain between 1% and 20% of a suitable thickening agent, such as those described above, and, optionally, emulsifiers and water.

Additives usually found in compositions topical, as preservatives (for example, methyl and ethyl paraben), dyes and perfumes can be included in any of the formulations described here.

Application Method

The effective amount of the compounds of formula I, used topically will vary depending on particular circumstances of application, the duration of the exposure and considerations of this kind. Generally, the amount will fluctuate between 0.01 microgram and 50 milligrams of the compounds of formula I, per square centimeter of epidermal area. The amount of topical composition (the compounds of formula I, and vehicle) applied on the affected area is easily determined in function of the amount of the compounds of formula I, contained.

The following examples illustrate and support the invention and should not be considered limiting the scope of the same. They have been based on the use of dobesilate as a compound covered by the formula I of the invention.

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Examples

Example one

2,5-dihydroxybenzene sulfonic acid test in photo aged skin

Potassium salt has been used for this study of formulated 2,5-dihydroxybenzene sulfonic acid 5% cream, as this type of formulation is a usual procedure for topical skin treatment. As phase Water cream we used distilled water. The fatty phase of it can be constituted by cetyl alcohol, alcohol stearyl or petrolatum. Span is an effective emulsifier in Creation of the cream.

The following example illustrates the formulation of an effective cream in the topical treatment of photoaging cutaneous and should not be considered limiting the scope of the invention.

Active ingredient: potassium acid salt 2,5% dihydroxybenzene sulfonic acid 5% Excipients: cetyl alcohol (2.5%), stearyl alcohol (2.5%), petrolatum liquid (30%), Vaseline Plante (20%), oleate sorbate (5%) and water distilled (c.s.p 100 gr).

Continuous topical skin treatment Photo-aged human with this cream, (2 times a day for 3 months) (Figure 1A), produces a decrease in wrinkles and disappearance of actinic lentigo areas, as shown by the Figure 1B The clearance of skin hyperpigmentation after application of 2,5-dihydroxybenzene sulfonic acid can justify its use to treat melanic dyschromias with hyperpigmentation as occurs, among other pathologies, in the spot Mongolian, Ota nevus, Ito nevus, Becker nevus, the ephelids (freckles), malignant lentigo-melanoma, the spot coffee with milk or melasma (chloasma).

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Example 2

Effect of 2,5-dihydroxybenzene sulfonate on seborrheic keratosis and viral warts

Topical treatment with the cream above described (twice a day for 11 days) of human skin (baseline conditions shown in Figure 2A) produces a decrease in seborrheic keratosis (large circle) as well as viral warts (small circle), as shown in the figure 2B.

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Example 3

Effect of 2,5-dihydroxybenzene sulfonic acid in hair growth

Potassium salt has been used for this study of formulated 2,5-dihydroxybenzene sulfonic acid in the form of cream, of identical composition to that used in Examples 1 and 2.

Topical treatment continued with this cream (2 times a day for 3 months) causes hair to disappear in the application area as shown in Figure 3B.

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Example 4

2,5-dihydroxybenzene sulfonic acid test in adipogenesis

To demonstrate the new mechanism anti-adipogenic acid 2,5-dihydroxybenzene sulfonic we have used the 3T3L1 preadipocyte cell line. The preadipocytes were planted in a six-well plate where they grew to converge in a Standard culture medium [Dulbecco's Essential Medium (DEM)], supplemented with 1.5 g / l of sodium bicarbonate, non-essential amino acids and 30% fetal bovine serum. In three of the wells were added to the acid culture medium 2,5-dihydroxybenzene sulfonic acid (25 µM) during 7 days. The culture medium was renewed every two days. After seven days, adipocyte differentiation began in the six wells adding dexamethasone (250 µM), 1,1-methyl-3-isobutylxanthine (0.5 mM) and insulin (160 nM) for two days, after which replaced the culture medium with another culture medium containing insulin (160 nM) for five days. In three of the wells kept the acid treatment 2,5-dihydroxybenzene sulfonic (25 µM). The middle Cultivation was renewed every two days.

After 12 days, adipogenesis was determined by staining with Oil Red O to see the cytoplasmic triglyceride accumulation. The cells were washed with phosphate buffer (PBS), fixed with paraformaldehyde to 4% and stained for thirty minutes with Oil Red O. To quantify lipid accumulation wasopropanol was used to extract the dye from the cells, measuring the absorbance of the same at 510 nm in a cytometer.

When 3T3L1 cells are treated (preadipocytes) with 2,5-dihydroxybenzene acid sulphonic (25 µM) for 12 days a very low decrease occurs significant number of differentiated preadipocytes in adipocytes, as depicted in Figure 3. Figure 4A corresponds to a control culture where most cells are  adipocytes containing triglyceride deposits. Figure 4B shows a culture treated with acid 2,5-dihydroxybenzene sulfonic. These cells, in a large proportion, have an undifferentiated appearance (preadipocytes) with low accumulation of triglycerides in the cytoplasm. Figure 5 represents a histogram corresponding to the quantification of triglycerides (detected cytometrically by Oil Red O) absorbance in three control crops and three cultures treated with the compound 2,5-dihydroxybenzene sulfonic.

This example shows that the acid 2,5-dihydroxybenzene sulfonic inhibits significantly adipogenesis.

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Example 5

After treatment with the composition of the invention, as can be seen in figure 6, the reversal of solar lentigines after treatment for two weeks with cream dobesilate. A, before treatment. B, after treatment

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Example 6

Following the same methodology explained in the Example 4, the effect of the gentisic acid was evaluated. differentiation of pre-adipocytes and adipogenesis The% absorbance at 510 is represented on the Y axis nm, the left column being the control (without treatment) and the column on the right the result of the acid treatment Gentysic It is clearly shown that the geneticist inhibits the differentiation of preadipocytes to adipocytes as well as the adipogenesis as it prevents the accumulation of lipids in the cells.

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Example 7

Inhibition by the gentisic acid of the differentiation of pre-adipocytes and adipogenesis. The photo on the left is the control and the right is the result of treatment with gentisic acid for two weeks.

Claims (7)

1. Use of derivatives 2,5-dihydroxybenzene represented by the formula I 5 in the which: R_ {1} in each case is selected so independent such as -OH or -OR2; Y is -SO3H, -SO3 {-}. X +, -SO 3 R 3, -PO 3 H, -PO 3 - - X +, -PO 3 R 3, -CO 2 H, -CO 2 - X + or -CO 2 R 3; X + is an organic or inorganic cation; R2 is a low alkyl group, a group aryl, an arylalkyl group, an alkylsulfonyl group, a group arylsulfonyl, a group alkylarylsulfonyl, a group arylalquisulfonyl, an aryloxyalkyl group, a group alkylcarbonyl or an arylcarbonyl group; R 3 is a low alkyl group, a group aryl, an arylalkyl group or an alkylaryl group; a is an integer between 0 and 6; the cation X + in the compound of formula (I) it can be any physiologically acceptable cation known in the state of the art; the cation X + is selected so that the general charge of formula (I) is neutral, where the compound of formula I is 2.5 dihydroxybenzene sulfonic acid (Dobesilate) or gentisic acid or homogentisic acid or salts or esters thereof for preparation of a drug, medicine or compound intended for cosmetic treatment of obesity or excessive adipogenesis, the treatment of hirsutism and hypertrichosis and the treatment of viral warts. 2. Use of derivatives 2,5-dihydroxybenzene represented by the formula I, according to claim 1, wherein the compound of formula I is the 2,5-dihydroxybenzene sulfonic acid (Dobesilate) for preparation of a drug, medicine or compound intended for cosmetic treatment of any of the diseases included in the following group: viral warts, hirsutism, hypertrichosis, skin photoaging, skin pigmentation, skin hyperpigmentation or solar lentigines, or keratosis seborrheic 3. Use of 2,5-dihydroxybenzene derivatives represented by the formula I according to claim 1, wherein the substituent Y of formula I is SO 3 H, -SO 3 {-}. X +, -SO 3 R 3, -PO 3 H, -PO 3 {-}. X + or -PO 3 R 3 for the preparation of a drug, medicine or compound intended for cosmetic treatment of any of the diseases included in the following group: cutaneous photoaging, skin pigmentation, skin hyperpigmentation or solar lentigines, seborrheic keratosis, atopic dermatitis, contact dermatitis, skin wrinkles or actinic keratosis. 4. Use of a composition comprising the formula I for the preparation of a drug, medication or compound intended for the cosmetic treatment of any of the diseases included in the following group: obesity or excessive adipogenesis, viral warts, hypertrichosis and hirsutism 5. Use of a composition comprising the formula I for the preparation of a drug, medication or compound intended for therapeutic treatment of any of the diseases included in the following group: obesity or excessive adipogenesis, viral warts, hyperticosis, hirsutism, skin photoaging, skin pigmentation, hyperpigmentation cutaneous, seborrheic keratosis or solar lentigines. 6. Use of a composition comprising the formula I where the compound of formula I is 2,5-dihydroxybenzene sulfonic acid (Dobesilate) or the gentisic acid or homogentisic acid or salts or esters of these, for the elaboration of a drug, medication or compound intended for the therapeutic treatment of obesity or adipogenesis excessive 7. Use of a composition comprising the formula I where the compound of formula I is 2,5-dihydroxybenzene sulfonic acid (Dobesilate) for preparation of a drug, medicine or compound intended for therapeutic treatment of any of the diseases arranged in the following group: warts, virals, hypertrichosis, hirsutism, skin photoaging, skin pigmentation, skin hyperpigmentation, seborrheic keratosis or lentigines solar.