MXPA01009293A - Skin cosmetic composition - Google Patents

Abstract

Cosmetic skin compositions containing a dextran or maltodextrin and a weak carboxylic acid. Dextran enhances the anti-aging activity of the weak acids and reduces skin irritation that is sometimes caused by the weak acid active.

Description

COSMETIC COMPOSITION FOR SKIN FIELD OF THE INVENTION Cosmetic compositions are disclosed for human skin containing a dextran or maltodextrin and a weak carboxylic acid.

BACKGROUND OF THE INVENTION Cosmetic products, which improve the appearance of the skin, are enormously popular with consumers. Consumers often seek to alleviate or delay the signs of aged or photo-aged skin, such as fine lines and wrinkles, dry and hanging skin. Consumers also seek other benefits in addition to anti-aging. Some ingredients used in topical products are potentially irritating, especially for people with "sensitive skin", such irritation is commonly perceived as itching or burning. As an example, fatty acids and various other weak carboxylic fatty acids have been proven to provide cosmetic benefits, such as an improvement in the appearance of photo-damaged or naturally aged skin, light on the skin, treatment of age spots, etc. Unfortunately, its use at high concentrations can occasionally be associated with skin irritation, for example, a reddish appearance on the skin and an itching sensation after application. For aesthetic reasons, these active ingredients are usually supplied as oil-in-water emulsions. In practical terms, the final pH of the composition should be greater than 3 in order to avoid damaging skin tissues and unacceptable levels of irritation. Water-soluble weak acids, when supplied from an oil-in-water emulsion to an acidic pH, generally induce high levels of itching. Itching occurs immediately after application, reaches a maximum intensity usually in 5-8 minutes after application and then begins to reduce intensity. The irritation can be alleviated by reducing the amount of an active ingredient in the composition or by reducing the penetration of the active ingredient through the skin. A serious disadvantage of both aspects is that effectiveness is damaged. The irritation related to the weak acid can be reduced by raising the pH of the composition, but this method produces reduced efficiency due to a reduced penetration of acid through the skin. It is desirable to reduce or eliminate the potential irritation of weak acids while maintaining their efficacy. Therefore, there is a need for a composition and method that prevents or reduces skin irritation. Coury et al. (U.S. Patent 5,618,850) describe cosmetic compositions containing polyhydroxy acids conjugated to the dextran polymer. EP 691126 (Beiersdorf) describes cosmetic compositions with low potential for itching for the treatment of sensitive skin. The compositions contain pigment to kidnapping agent, AHA. A serious disadvantage of the descriptions of Coury and Beirsdorf is that the conjugation c sequestration significantly reduces the supply of the active and SL efficacy. Most of the assets in current use have a molecular weight of less than 1000 Daltons. The penetration of active substances through the skin is strongly reduced with its molecular weight (Ref Trasdermal Delivery of Drugs; Volume III, pp. 7-8 Agis F. D1 (WO 98/5634) describes a cosmetic composition for topical application to the skin, which comprises a cyclodextrin compound and a salicylic acid or salicylic acid derivative in the form of a water-in-oil emulsion, D4 (Drug and Cosmetic Industry, January 1994, page 24) describes the use of alpha hydroxy acids to treat dry and relatively dry skin and clean pores Kydonieus and Bret Berner (ed) CRC Press, Inc. Boca Raton Fl, 1987. Polymers have a high molecular weight (> 1000 Dalton). active with the dextran polymer will make it a high molecular weight molecule and therefore, will significantly reduce the penetration.The weak acid sequestration will reduce the amount of acid that may be available for supply.

Another aspect to reduce itching is to formulate the acid with a strong alkali metal base. Yu et al. (U.S. Patent 4,105,783) suggested the use of ammonium hydroxide or an organic base. Unfortunately, this method raises the pH of the composition and reduces the ability of the weak acid to penetrate the skin, thereby reducing its effectiveness (see, Sah et al., In J. Cosmet, Sci 49, 257-273, 1998). There is a clear need for a cosmetic composition with a weak acid that reduces itching but does not reduce the dermal supply. The publication of LAREX (March 23, 1998) describes the use of a polysaccharide (arabinogalactan) to increase e! Exfoliation operation of a skin care lotion containing alpha hydroxy acid by 80% and do this without elevated irritation. However, the present invention seeks to reduce irritation, instead of merely not increasing it. It has been found that, as part of the present invention, other polysaccharides, dextran and maltodextrin, reduce the irritation associated with the use of weak carboxylic acids, while e. arabinogaiactane does not have this effect. In addition, it has been found that dextran, unlike arabinogalactan, improves the anti-aging efficacy of hydroxy acids.

COMPENDIUM OF THE INVENTION According to the present invention, there is provided a cosmetic composition for the skin comprising: (i) from 0.5 to 20% by weight of the composition of a dextran or maltodextrin; (ii) from 0.01 to 20% by weight of the composition of a weak carboxylic acid having a pKa approximately above 2; and (iii) a cosmetically acceptable vehicle. The invention also includes cosmetic methods for stimulating the synthesis of collagen through the differentiation of fibroblasts and keratinocytes in the skin, by applying the composition of the invention to the skin. The invention also includes a cosmetic method for treating or delaying aged, chrono-aged, photo-aged, dry, scratched or wrinkled skin, increasing the firmness and flexibility of > Corneal extract, improve the tone of the skin, and generally raise the quality of the skin by applying the composition of the skin to the skin. The invention further provides a method for reducing skin irritation caused by topical application of a composition containing a weak carboxylic acid, the method comprising topically applying a dextran or maltodextrin in a pharmaceutically acceptable vehicle. Thus, according to the method of the invention, dextran or maltodextrin can be co-present with weak acid in the same composition, or can be applied from a separate composition.

DETAILED DESCRIPTION OF THE INVENTION All amounts are by weight of the oil emulsion er water, unless otherwise specified. The term "skin", as used herein, includes the foot of the face, neck, chest, back, arms, armpits, hands and scalp. The terms "irritation", "itching", and "burn" "inflammation", and "reddish", as used in the present, sor synonyms and are used interchangeably. The molecular weight is expressed in Dalton (D). The numerical terms followed by the letters "KD" denote the molecular weight of a compound, which will be read as the numerical term X 1,000, for example, 10 KD means a molecular weight of 10,000 d).

Dextran Both dextran and maltodextrin are glucose homopolymers. Dextran in a beta-1, 6-glucan with several side chains of glucose, linked mainly to the main chain of the macromolecule through 1,3-bonds but, partly also by 1,4- and 1,2-bonds. On average, 95% of glucose residues are present in the main chain. This is produced through certain bacteria from a nutrient medium containing sucrose. The molecular weight of the dextrans generally ranges from 5 KD to 2,000 KD, preferably from 5, KD to 1,000 KD, to maintain anti-irritation efficacy, and even to minimize and increase the viscosity of the formulation.

Maltodextrin Maltodextrins, (C6H10? 5) n-H2O (CAS Reg. No. 9050-36-6) are non-sweet nutritive saccharide polymers consisting of D-glucose units linked primarily through alpha-1, 4-bonds, having a DE (dextrose equivalence) less than 20. They are prepared as a white powder c concentrated solution through partial hydrolysis of corn starch with safe and suitable acids and / or enzymes. The proper source of maltodextrin is Maltrin © from Grain Processing Corp Matrin® contains maltodextrin and corn syrup solids. The amount of dextran or maltodextrin in the composition of the invention ranges from 0.5 to 20%, preferably from 1 to 15%, most preferably from 1 to 10% by weight of the composition.

Weak Carboxylic Acid A weak carboxylic acid for use in the compositions of the invention is an acid with a dissociation constant, pKa, of about 2. Preferably, the pKa is above about 3, most preferably on the scale of about 3 to 5 The concept of pKa An acid is a species that has a tendency to lose a proton, while a base is a species that has the tendency to accept a proton. In this way for each acid. HA, there is a conjugate base A ": HA H + + A " In this manner, the lactic acid-lactate ion is an example of a pair of acid-base conjugate. The acids thus defined can only manifest their properties by reacting with bases. In aqueous solutions, acids react with water, this last acting as a base: HA + H20 H30 + + A " Quantitatively, the acid resistance of HA, with relation to the water base resistance, is given by the expression of equilibrium constant by means of the equation: K = [H3O +] [A-] / [H20] [HA] where the parentheses denote molar concentrations.

Since almost all measurements are made in diluted aqueous dilution, the concentration of water remains essentially constant and its activity can be taken as a unit. Let H + represent the solvated proton, then we have: Ka = [H +] [A "] / [HA] where Ka is the acid dissociation (or ionization) constant. This equation can be written in the form of: Ka = pH + Reg. [HA] / [A] where pKa is the negative logarithm of Ka, and is equal to the pH at which the concentrations of HA and A "are the same.The pKaa for alpha hydroxy acids is generally between 2-4 for monocarboxylic acids between 3-5 for alpha amino acids between 2-3, for salicylic acid it is 3.0 The pKa of a weak water-soluble acid is obtained by titrating it with a strong base such as sodium hydroxide (NaOH) The interception at the midpoint of the titration is To say, the point where 0.5 molar equivalents of the base have been added, is numerically equal to the acid pKa.A procedure to determine the pKa for a known debi acid is as follows: Materials Sample of pure acid for which pKa is to be determined distilled deionized water free of CO2 (prepared by boiling deionized distilled water for 5 minutes); Volumetric standard 0.1 N commercial NaOH, certified by 0.1005-0.0995 N, eg, Fisher Scientific SS276; calibrated glass test tube of 10C ml; Erlenmeyer flask 125 ml; pH meter, for example, from Corning Model 140 with electrode of standard combinations for pH; pH regulators, pH values of 4.00, 7.00, and 10.00 certified for pH units +0.01 to 25, for example Fisher Scientific SB101, SB107, and a SB115 magnetic stirrer.

Method Ensure that all glassware and equipment are clean Wash acid if necessary. Prepare at least 50 ml of a normal solution of 0.1 of acid for which the pKa value in distilled water free of C02 is determined. Avoid introducing CO2 into the solution avoiding excessive agitation. Cover the final solution until used. Calibrate the pH meter using three pH regulators, pH 7.00, 3.00 and 10.00, in accordance with the instructions of the manufacturer of the pH meter. Wipe the electrode with distilled water between the samples. Fill the pipette with a standard 0.1 N NaOH solution. Add 50.0 ml of a 0.1 N solution of acid to the 125 ml Erlenmeyer flask. Add the stir bar to the Erlenmeyer flask.

Insert the electrode into the acid solution. Place and secure the electrode so that it does not interfere with the stir bar. Record the initial pH. Begin a moderate agitation so that the pH reading is not affected. Place the pipette in the flask to allow the incremental addition of 0.1 N of standard NaOH to a 0.1 N solution of acid. Check the initial pH and start the addition of the base in increase. Pretend to record pH changes from 0.2 to 0.3 units or volume increases of approximately 5 ml, whichever comes first. Continue increasing additions until at least 60 ml of the base have been added and the sharp change in pH levels. Graph the data with the volume of the base as the x-axis and pH as the y-axis. Graph the observed points and draw a line through them. Determine the volume of the aggregate base to obtain the equivalence point, that is, the volume at which the normal equivalent ur of the base has been added and the acid has been completely neutralized; When the steep portion of the curve is vertical, the volume of equivalence point corresponds to the volume of the base in the vertical portion of the curve. If the steep portion of the curve is not vertical, the point of equivalence can be obtained by locating the volumes of the base in the two final points that enclose the steep change in the pH value. The mean of the two volumes is the equivalence point. To determine the p'Ka, first locate the midpoint of the titration by dividing by half (ie, by two) the volume of the base at the equivalence point. The midpoint of the titration is the point at which 0.5 normal equivalents of the base have been added, and the acid has been neutralized (50%). The pH corresponding to the midpoint of the titration is the pKa of the acid. This is the pH at which 50% of the acid has been neutralized, that is, and the molecule exists 50% in the non-ionized form and 50% as the anion. Examples of suitable weak carboxylic acids include, but are not limited to: alpha- or beta-hydroxy acids, dicarboxylic acids, tricarboxylic acids, ascorbic acid, oxamic acid and mixtures thereof. Preferred carboxylic acids, due to their anti-aging efficacy, are: ACID p_Ka glycolic 3.8 lactic 3.8 malic 3.4 beta-hydroxybutyric 4.7 acetic 4.75 succinic 4.2 citric 3.1 ascorbic 4.1 salicylic 3.0 oxmic 2.4 and mixtures thereof.

The amount of weak acid in the composition of the invention ranges from 0.01 to 20%, preferably from 1 to 15%, and most preferably from 2 to 12% by weight of the composition. concentrations below 2% of the acid, there is a minimum picacidad and the anti-aging effectiveness does not increase significantly above 12%. It should be understood that depending on the pH of the composition the acid may be present as a salt, for example, ammonium or potassium or sodium salt. Although the compositions of the invention may have any pH in the general scale of 2.5 to 10, the compositions of the invention are particularly useful when they are at an acidic pH preferably 3-6 and most preferably at a pH of 3-5, since said compositions, while effective, are particularly irritating. The compositions according to the invention comprise a cosmetically acceptable vehicle to act as a dispersing diluent or carrier for the weak carboxylic acid and dextran or maltodextrin, in order to facilitate its distribution when the composition is applied to the skin. The vehicle can be aqueous or an emulsion. The water when present is in amounts that can vary from 5 to 99%, preferably from 40 to 90%, optimally from 50 to 85% by weight. According to the present invention, the vehicle preferably is at least 50% water, by weight of vehicle. The compositions of the invention are preferably oil-water emulsions, in order to improve the dermal supply of hydroxy acids (see, Sah et al, in J. Cosmet, Sci.49, 257-273, 1998). Said improved delivery is often accompanied by increased irritation / itching, making the use of dextran in such emulsions particularly critical. Preferred oil-in-water emulsions according to the present invention, the water comprises at least 50% by weight of the emulsion of the invention, most preferably from 50 to 85% by weight of the composition. In addition to water, relatively volatile solvents can also serve as carriers within the compositions of the present invention. Most preferred are monohydric alkanois of 1 to 3 carbon atoms. These include ethyl alcohol, methyl alcohol and isopropyl alcohol. The amount of monohydric alcohol can vary from 1 to 70%, preferably from 10 to 50%. optimally between 15 and 40% by weight. The emollient materials can also serve as cosmetically acceptable vehicles. These can be in the form of silicone oils and synthetic esters. The amounts of the emollients can vary from 0.1 to 50%, preferably from 1 to 20% by weight. Silicone oils can be divided into the volatile and non-volatile variety. The term "volatile", as used herein, refers to those materials that have a measurable vapor pressure at room temperature. The volatile silicone oils are preferably selected from cyclic or linear polydimethylsiloxanes containing from 3 to 9, preferably from 4 to 5, silicon atoms. Volatile linear silicone materials generally have viscosities less than 5 MPas at 25 ° C. while cyclic materials typically have viscosities less than about 10 MPas. The volatile nc sylcone oils useful as an emollient material include polyalkylsiloxanes, polyalkylarylsiloxanes and polyether-siloxane copolymers. The essentially non-volatile polyalkylsiloxanes useful herein include, for example, polydimethylsiloxanes at viscosities of about 5 to about 25 million MPas at 25 ° C. Among the preferred nonvolatile emollients useful in the compositions herein are the polydimethylsiloxanes having viscosities of about 10 to about 400 MPas at 25 ° C. Among the ester emollients are: (1) Alkenyl or alkyl esters of fatty acids having from 10 to 20 carbon atoms, examples of which include isoaraquidyl neopentanoate, and isonanonoate of Sononyl, oleyl myristate, oleyl stearate and oleyl oleate. (2) Ester-esters such as esters of fatty acids of ethoxylated fatty alcohols. (3) Polyhydric alcohol esters. Esters of mono- and di-fatty acid of ethylene glycol, esters of mono- and digraso-acid of diethylene glycol, esters of mono- and digraso-acid of polyethylene glycol (200-6000), esters of mono- and di-fatty acid of glycol propylene, propylene glycol monooleate 2000, polypropylene glycer monostearate 2000 ethoxylated propylene glycol monostearate, glyceryl mono- and di-fatty acid esters polyglycerol poly-fatty esters. Ethoxylated glyceryl monostearate, 1,3-butylene glycol monostearate 1,3-butylene glycol monostearate, polyoxyethylene polyol fatty acid ester, sorbitan fatty acid esters, and polyoxyethylene lobran fatty acid esters are polyhydric alcohol esters satisfactory. (4) Wax esters such as beeswax, whale sperm, myristyl myristate, stearyl stearate and arachidyl behenate. (5) Esterols, of which the fatty acid esters of cholesterol are examples thereof. Fatty acids having from 10 to 30 carbon atoms can also be included as cosmetically acceptable vehicles for the compositions of this invention. Examples of this category are pelargonic, lauric, myristic acids. palmitic, stearic, isostearic, hydroxystearic, oleic, ricinoleic, arachidic, behenic, and erucic linoleic.

Humidifiers of the polyhydric alcohol type can also be employed as cosmetically acceptable carriers in the compositions of this invention. The humectant helps to increase the effectiveness of the emollient, reduces scaling, stimulates the removal of scale development and improves the skin feel. Typical polyhydric alcohols include glycerol, polyalkylene glycols, and most preferably alkyl polymers and their derivatives, including propylene glycol, dipropylenic glycol, polypropylene glycol, polyethylene glycol and its derivatives, sorbitol hydroxypropyl sorbitol, hexylene glycol, 1,3-butylene glycol, 1,2,6-hexanetriol, ethoxylated glycerol, propoxylated glycerol and mixtures thereof. For best results, the humectant preferably propylene glycol or sodium hyaluronate. The amount of humectant can vary in any form from 0.5 to 30%, preferably from 1 s to 15% by weight of the composition. Thickening agents can also be used as part of the cosmetically acceptable vehicle of the compositions according to the present invention. Typical thickeners include entangled acrylates (e.g., Carbopol® 982) hydrophobically modified acrylates (e.g., Carbopol® 1382). cellulose derivatives and natural gums. Useful cellulose derivatives include sodium carboxymethylcellulose, hydroxypropylmethyl cellulose, hydroxypropylcellulose, hydroxyethylcellulose, ethylcellulose and hydroxymethylcellulose. Natural gums suitable for the present invention include guar gum, xanthan, sclerotium carrageenan, pectin and combinations of these gums. The amounts of the thickener can vary from 0.0001 to 5%, usually from 0.001 to 1%, optimally from 0.01 to 0.5% by weight. Collectively, the water, solvents, silicones, esters, fatty acids, humectants and / or thickeners will constitute the cosmetically acceptable vehicle from 1 to 99.9%, preferably from 80 to 99% or by weight. An oil or oily material may be present, together with ur emulsifier to provide either a water-in-oil emulsion or an oil-in-water emulsion, depending greatly on the average hydrophilic-lipophilic balance (HLB) of the emulsifier employed. Surfactants may also be present in the cosmetic compositions of the present invention. The total concentration of the surfactant will vary from 0.1 to 40%, preferably from 1 to 20%, optimally from 1 to 5% by weight of the composition. The surfactant may be selected from the group consisting of anionic, nonionic, cationic and amphoteric surfactants. Particularly preferred nonionic surfactants are those with a fatty alcohol of 10 to 20 carbon atoms or hydrophobic acid condensed with 2 to 100 moles of ethylene oxide or propylene oxide per mole of hydrophobe; alkyl phenols of 2 to 10 carbon atoms condensed with 2 to 20 moles of alkylene oxide; esters of mono- and di-fatty acid of ethylene glycol monoglyceride of fatty acid; mono- and di-fatty acids of 8 to 20 carbon atoms of sorbitan; block copolymers (ethylene oxide / propylene oxide); and polyoxyethylene sorbitan, as well as combinations thereof. Alkyl polyglycosides and saccharide fatty amides (eg, methyl gluconamides) also are suitable nonionic surfactants. Preferred anionic surfactants include alkyl ether sulfate soap and sulfonates, alkyl sulfates and sulfonates. alkylbenzenesulfonates, alkyl and dialkyl sulfosuccinates, acytonate salts of 8 to 20 carbon atoms, acyl glutamates, alkyl ether phosphates of 8 to 20 carbon atoms, and combinations thereof. Various types of additional active ingredients may be present in the cosmetic compositions of the present invention. The active ingredients are defined as beneficial agents for the foot other than emollients and other than ingredients that merely improve the physical characteristics of the composition. category, general examples include additional ingredients against bait and sunscreens. Sunscreens include those materials commonly used to block ultraviolet light. Illustrative examples are the derivatives of PABA, cinnamate and salicylate. For example avobenzophenone (Parsol 1789®), octyl methoxycinnamate and 2-hydroxy-4-methoxy-benzophenone (also known as oxybenzone) may be used.Octyl methoxycinnamate and 2-hydroxy-4-methoxybenzophenone are commercially available under the trademarks of Parsol MCX and Benzophenone-3 respectively The exact amount of sunscreens used in the compositions may vary depending on the degree of protection desired from the sun's UV radiation.Preferably, the cosmetic composition is protected against the development of potentially dangerous microorganisms Thus, preservatives are desirable Suitable preservatives include p-hydroxybenzoic acid alkyl esters derived from hydantoin, propionate salts, and a variety of quaternary ammonium compounds The particularly preferred preservatives of this invention are methylparaben propylparaben, phenoxyethanol, and benzyl alcohol, the conservatives usually they will be employed in amounts ranging from about 0.1% to 2% by weight of the composition. The composition according to the invention is primarily intended for a product for topical application to human skin especially as an agent for improving the appearance of aged or photo-aged foot. In use, an amount of the composition, for example from 1 to 100 ml, is applied to the exposed areas of the skin, from a suitable container or applicator and, if necessary, it is then spread over and / or rubbed on. the skin using your hand or fingers c a suitable device.

Form v Product Packaging: The cosmetic skin composition of the invention can be in any form, for example, a toner, gel, lotion, a fluid cream, or a cream can be formulated as a toner. The composition can be packed in a suitable container or container to promote its viscosity and intended use by the consumer. For example, a fluid lotion or cream may be packaged in a bottle or rolling ball applicator or ur aerosol device driven by a propellant, or a container equipped with a pump suitable for finger operation. When the composition is a cream, it can simply be stored in a non-deformable bottle or container that can be compressed, such as a tube or a jar with a lid. The invention therefore also provides a closed container or container containing a cosmetically acceptable composition as defined herein. The composition may also be included in capsules such as those described in U.S. Patent No. 5,063,057 incorporated herein by reference. The following specific examples further illustrate the invention, but the invention is not limited thereto.

List of Suppliers Active ingredient Supplier Dextrana Sigma, Dextran Products Corp.

Grain Maltodextrin, Processinf Corp. Arabinogalactan Larex, Inc. DuPont Glycol Acid Lactic Acid Purac America, Inc. Sigma Hydrocortisone Sigma Succinic Acid (Water Soluble) EXAMPLE 1 This example measured the itching caused by formulations containing glycolic acid. Procedure for the in vivo itching test: This was a double blind randomized study, where each subject tested a test formulation and a control formulation or two test formulations at the nasolabial versus lateral commissures. During the qualification phase, each subject was evaluated with an 8% glycolic acid test against a vehicle control (0% glycolic). Subjects with balanced right / left sensitivity to glycolic acid were rated. A maximum of 20 qualified subjects (minimum of 15) was used in each subsequent trial. A comparison was made in pairs each day of testing, with a minimum of 3 days between the test of itching through the study. The subjects were conducted with a regimen of washing with the Ivory soap immediately before the product test to improve the itching response. Any of the subjects who experienced any itching / burning at the test sites immediately prior to application of the product were not given any products. Then, the study staff applied a test formulation and control or test formulation simultaneously to the appropriate left / right test site, and moderately but thoroughly was rubbed into it. The subjects compared the itching potential of the two formulations over a 7.5 minute period using a self-determination questionnaire. Prognosis of itching / burning: The degree of itching / burning perceived on the left and right internal cheek and fold of the nose was evaluated using the following scale at the times indicated in the Tables below: 0 - no itching / burning; 1 - very light itching / burning 2 - . 2 - light burning / itching; 3 - moderate itching / burning; 4-moderately high-burning / burning; 5 - itching / burning high; 6 - extreme burning / burning. Determination of Statistical Importance: At each evaluation time point after the baseline, the t test was performed in pairs, parametric (two extremes), to compare the degree of change of attribute from the baseline between each treatment comprising a comparison test in pairs, with the subject acting as a block in these analyzes. (Ref. Statica Methods, Snedecor and Cochran, Iowa State University Press, 7th Edition, 1980, pp. 84-86). The test can be implemented using the MEANS procedure of the SAS software with the options T and PRC specified. Forced selection of itching / burning: at each evaluation point (0, 2.5, 5.0 and 7.5 min), the response to the determination of forced selection, "which side of the face has more itching" ?, was analyzed as follows: the number of subjects who selected treatment A was compared with the number of subjects subjects who selected treatment B using a t test in parametric pairs (two extremes). The statistical significance was determined in p <; _ 0.1. The results of several pairwise comparisons using this termination method are shown in Tables 1B, 2B, 3B and 4B (see below). An oil-in-water emulsion cream (Base Formula A) was prepared.

* Unless otherwise noted, the active levels were approximately 100%. The itching / burning of Base Formula A with or without 8% glycolic acid was tested using the in vivo itch test. The data that was obtained is summarized in Tables 1A and 1B: Table 1A Prognosis to itching / burn p < 0.05 Table 1B Forced selection for itching / burn:? Q? E side is worse ' Results 7.5 minutes after the application * p < 0.05 The propensity for itching / burning of glycolic at a level of 8% and 4% was compared. The results that were obtained are summarized in Table 1C.

Table 1C Prognosis to Itching / Burn * p < 0.05 It can be seen from results 1A-1C that 8% glycolic acid at a pH of 3.8 is significantly more itchy than either the base formulation or 4% glycolic acid. Although, the itching can be reduced by increasing the pH or reducing the level of active, such changes in the composition significantly affect the supply to the dermis and consequently, the effectiveness of the active.

EXAMPLE 2 This example measured the effect of 10 KD dextran on itching by glycolic acid at a pH of 3.8 in the base formula A. The in vivo itch test and the base A formula are described in Example 1.

The base A formula was prepared without the glycolic acid, base and dextran. The dextran was solubilized in a separate baseline containing glycolic acid + base (ammonium hydroxide) and small water level of the formulation (not more than 5% necessary), thus, the original base A formula was originally made with 5% less water. The glycolic acid / dextran solution was then added to the base formula A during the cooling step (usually at a temperature of about 45 ° C). The results that were obtained are summarized in Tables 2A, 2B and 2C.

Table 2A Prognosis to Itching / Burn p < 0.1 Table 2B Forced selection for itching / burn: What is worse? Results 2.5 minutes after the application Base A Formula + Base Formula A 8% glycolic + 5% + 8% Glycolic dextran 10KD (pH3.8) (pH 3.8) Numbers of subjects indicating more discomfort 5 14 * ( itching / burn) p < 0.1 Table 2C Prognosis to Itching / Burn It can be seen from the results of Tables 2A and 2E that dextran significantly reduced the itch / burn propensity of the base A formula containing 8% glycolic acid. In Table 2C, the difference in the picacious response of the two formulations was not statistically significant leading to the conclusion that dextran reduced the itch of the 8% glycolic acid formulation to that of the 4% acid formulation. glycolic EXAMPLE 3 This example tested the effect of 10 KD dextran on picazor by succinic acid at a pH of 3.8 in the base formula A. This test procedure and the base formula A are described in Example 1. The test formulations were prepared as it was described in Example 2, except that succinic acid was used instead of glycolic acid. The results obtained were summarized in Tables 3A and 3B.

Table 3A Prognosis to Itching / Burn p < 0.1 Table 3B i ón / uemadura: Which side is worse? * p < 0.05 It can be seen from the results in Tables 3A and 3E that the dextran significantly reduced the itch / burn propensity of the base A formula containing 8% succinic acid 25 minutes after application.

EXAMPLE 4 This example tested the effect of dextran on itching glycolic acid in a lotion. The test is described in Example 1. An oil-in-water lotion was prepared (base B formula, having the following formula * Unless otherwise noted, asset levels are approximately 100%.

The emulsion concentrate was made using all the ingredients, except glycolic / base / dextran and without all the water. In a separate precipitate, glycol + base + + dextran + about 5% of the total water were combined and mixed until the dextran is completely solubilized. This mixture was then added to the emulsion. Then, the pH was adjusted to the correct pH using a base, and then the remainder of the water was added to a sufficient amount of 100%. The results that were obtained are summarized in Tables 4A and 4B.

Table 4A Prognosis to Itching / Burn Table 4B Forced selection for itching / burn: Which side is worse? Results 2.5 minutes after the application It can be seen from the results in Tables 4A and 4E that dextran reduced the itch / burn propensity of the base B formula containing 8% glycolic acid.

EXAMPLE 5 Additional dextran molecules were tested for SL ability to reduce itching. The test procedure and formula A are described in Example 1. The base C formula was as follows: The results that were obtained are summarized in Tables 5A, 5B and 5C.

Table 5A Prognosis to Itching / Burn p < 0.1 Table 5B Prognosis to Itching / Burn: Dextrana 10K and Dextrana 464K Table 5C Projection to the Itching / Burn Dextrana 10 KD and Dextrana It can be seen from the results in Tables 5A, 5B and 5C that the dextrans of variable molecular weights reduce the itching equally well.

COMPARATIVE EXAMPLE 6 This example tested several compounds for their ability to reduce itching. The test procedure and the base formula are described in Example 1. The results that were obtained are summarized in Tables 6A and 6B.

Table 6A Hydrocortisone Table 6B Arabinogalactan The results in Tables 6A and 6B show that neither hydrocortisone nor arabinogalactan reduces itching. Actually, the addition of 5% arabinolactane (Table 6B; slightly improves the itching of the anti-aging cream.

EXAMPLE 7 This example tested the effect of dextran on the delivery of several active molecules to the skin layers. Procedure: the supply of active substances to the dermis was measured through the in vitro percutaneous absorption test (PCA). The tests were performed using pig skin with dermatome and Bronaugh flow cells. The dorsal skin of female pig at an age of 3-4 weeks, rinsed with water, was only obtained from Buckshire Farms. The skins were stored at -70 ° C until used. They were frozen at room temperature, shaved moderately with an electric Norelco shaver, sliced to a thickness of 510 μm using Padgett Dermatome, drilled in 18 mm discs with a perforated cork, and mounted in Bronaugh diffusion cells at 37 ° C, pH 7.5, balanced pH regulator of Hank's flowing saltse at 5 ml / minute. After 30 minutes of equilibrium, transepidermal water loss was determined using a ServoMed EP1 evaporimeter. The skin discs that allowed water losses of > 5 g / m2 per hour were replaced. The skin discs were dosed with 2 μL of product containing the unlabeled active with an insignificant weight of the radio-labeled active with 3 H or 14 C at about 30 microcuris / grams of product. The dose was delivered through a displaced volume pipette and spread on the exposed skin surface to a diameter of & mm either with a latex finger stretched on a cotton tip applicator. The contact times were 6 hours, with the receiver fluid being sampled at intervals of 1 or 2 hours in clinker bottles. At the end point, the skin surface was rinsed in triplicate with aliquots of approximately 1 ml of water, the skin discs were removed from the apparatus, and 1/3 of tissue paper was stained (Kim Wipe). To the upper surface, an adhesive tape was placed 9 times with Scotch transparent tape to obtain the stratum corneum, and the epidermis was separated from the dermis with a scalpel. The analysis through liquid scintillation spectrometry included all the samples necessary to represent complete equilibrium and recovery of the radio-labeled material including the product retained in the applicator during delivery, the rinse water and the excess were removed from the tissue, of the stratum corneum with the adhesive strip, epidermis, dermis (counted after the NCS digestion), receptor fluid, empty Bronaugh cells, filter papers and rinsing pipettes. The rinse dose was determined. The theoretical applied dose was determined by subtracting the material retained on the applicator from the average measured radioactivity of a minimum of 6 heavy aliquots of 2 μl of the radiolabelled test product. The data will be reported as percentages of doses in tissue fractions. A p-value of <; _ 0.1 was considered statistically important. The effect of dextran on the supply was tested for the base A formula with either glycolic acid or succinic acid. The results obtained are summarized in Tables 7A and 7B.

TABLE 7A TABLE 7B It can be seen from the results in Tables 7A and 7E > that dextran did not adversely affect the supply of either glycolic acid or succinic acid to different layers of skin tissue. In fact, the presence of dextran led to a directional increase in the glycolic acid supply (Table 7A). In this way, the results of Examples 1-5 demonstrate that dextran reduced the application caused by weak acids. Other known anti-irritants, such as hydrocortisone, as well as other polysaccharides, arabinolactan, did not reduce the itching caused by weak carboxylic acids ( Comparative Example 6). Unlike the numerous aspects of the prior art, the addition of dextran did not adversely affect the supply of active towards the layers of the skin (Example 7). Examples 8-10 investigate an additional benefit of combining dextran with an active acid: the ability of dextran to improve the effectiveness against aging of acid assets.

EXAMPLE 8 This example investigated the effect of dextran on the ability of hydroxy acids to synthesize collagens in skin fibroblasts. Collagen is a predominant protein in the skin. This ee is synthesized through fibroblasts in the dermis. Collagen synthesis is reduced with aging or photodamage. Collagen I is first made as a precursor molecule called procollagen I. The high production of pro-collagen I is a marker of a high level of collagen in response to an application of test compound. Method: Neonatal human dermal fibroblasts were purchased from Clonetics Corp., San Diego, CA. All materials for cell culture were purchased from Life Technologies, NY. Cells were seeded (between passages 5-10) at a density of approximately 10,000 / cavity in the 48 internal cavities of a 96-well plate in DMEM (Eagle Modified Medium Dulbecco), a high glucose content, supplemented with 2 rniV of L-glutamine, 10% fetal bovine serum, and antibiotic and antifungal solutions. Then, cells were grown to confluence for 2 days. At the confluence, the medium was removed and the cells were washed with serum free DMEM, and each well was dosed with 200 μl of a solution of a serum free DMEM test compound. Each dosage was replicated in total € cavities. Test compounds were used at concentrations indicated in Table 8 below. The control did not contain ur test compound. After 24 hours, the solutions were removed and the cells re-dosed with 100 μl of the same solutions. After 24 hours, all solutions were removed, aprotinin was added at a concentration of 0.5% and the solutions stored until analysis at 4 ° C. For the analysis of pro-collagen I in the solutions, they were diluted in DMEM (approximately 20 μl of sample in 200 μl of DMEM). The BioRad slot stainer (BioRad Labs, CA) was fixed as indicated in the manufacturer's instructions. In brief, a nitroceful membrane and 3 sheets of filter paper were moistened in pH regulated saline with TRIS (TBS, pH 7.3) and assembled in the apparatus with the filter paper on the bottom and the membrane on top. 100 ml of TBS was added per well and filtered under vacuum. 100 μl of the cavity sample solution was loaded and filtered by gravity. The pro-collagen from the test solution was attached to a membrane at this point of procedure. The membrane was removed from the apparatus and a blocking solution (5% milk powder in D-PBS) was placed for 1 hour at room temperature or overnight at 4 ° C on a rotary shaker. The membrane was then incubated for 1.5 hours at room temperature or overnight at 4 ° C with 1.5 ml of mouse anti-human anti-human pro-collagen Ab (Chemicor MAB1912) in TBS with 0.1% BSA (ratio of antibody to pH / BSA buffer was 1: 100) in a sealed bag under agitation. The membrane was then removed; was washed 3 times for 5 minutes in TBS / 0.1% Tween. The membrane was then incubated for 1 hour at room temperature or overnight at 4 ° C in 2 ml of Ab conjugated with biotinylated anti-mouse peroxidase (Vector Labs) in TBS with 0.1% BSA (the ratio of antibody to pH / BSA buffer was 1: 1000) in a sealed bag with stirring. The membrane was washed 3 times for 5 minutes in TBS / 0.1% Tween. 3 ml of PBS were incubated with 30 μl of each of solutions A (avidin) and B (biotinylated horseradish peroxidase) of Vectastain Elite Kit (Vector Labs) for 30 minutes. The membrane was placed in the resulting solution for 30 minutes in a sealed bag with shaking. The membrane was then washed and removed 2 times for 5 minutes in TBS / 0.1% Tween. The membrane was then stained using the following solution: 12.5 me of 3-amino-9-ethylcarbazole (Sigma), 3.125 ml of N, N-dimethylformamide (Sigma), 21.5 ml of 0.2 M acetate pH buffer, pH 5.2 and 12.5 μl of H2O2. The membrane was stained until ur red / brown developed and the reaction was stopped with 2 washes of 10 minutes in running water. A stain transparency was prepared using a color copier. The color copy was scanned using a laser densitometer (Ultroscan XL from Pharmacia KLB). The percent increase was calculated as an optical density ratio of cells treated with a test compound on the x 100 control. The results obtained are summarized in Table 8.

Table 8 * p < 0.05 The results in Table 8 show that the combination of dextran and glycolic acid provides a significant increase in procollagen I, while the combination of arabinogalactan and glycolic acid did not.

EXAMPLE 9 This example investigated dextran's ability to induce potential differentiation of lactic acid keratinocyte. Keratinocytes, the main cell type in the epidermis, undergo a program of differentiation leading to the formation of corneocytes, which form the stratum corneum and provide a protective barrier against the loss of water and entry of dangerous substances and pathogens. A prominent feature of keratinocyte differentiation is the formation of a highly insoluble, entangled cover (CE) immediately below the membrane of the keratinocyte plasma. EC production of keratinocyte is catalyzed by transglutaminase-K enzyme (Tgase K), which interlaces certain precursor proteins in the cell. It has been reported that letinoic acid, an agent that is highly effective in improving the appearance of photo-aged foot (Weiss et al. JAMA, 259: 527, 1988), increases transglutaminase-K (also referred to as Tgase I) in The skin Therefore, the agents that increase the activity of TgaseA have the potential to provide benefits to the skin. Method: Normal human keratinocytes were plated in 96-well plates at 4000 cells / well and a growth medium of "goat" (KGM) obtained from Clonetics Corp. was grown. The cells were treated with test compounds at various concentrations. for 48 hours with an intermittent change of medium after 24 hours.All replication cavities were used for each test.At the end of the incubation period, two parameters were measured in the cells-I DNA and the transglutaminase protein. The DNA was measured using a matoco described by Rago and other Anal. Biochem 191: 31-34, 1990. The medium was aspirated from the plates, the cells were washed 3 times with regulated salt in their phosphate picon (PBS). cells were frozen and thawed 2 times for 5-10 minutes each time 100 μl of the Hoechst dye solution (hased Calbiochem) (1 μg / ml in PBS) was added to each cavity, the plate was covered with a sheet and allowed to settle at room temperature for 10 minutes. Then readings were taken in a Millipore Fluorescence Microplate Reader (ex / em 360/450 nm). The amount of DNA per cavity (a) was calculated using standards. II. The dye was removed and the cells were again rinsed 3 times with PBS to prepare the transglutaminase assay (Tgase). 200 μl of powdered Sir Carnation 5% fat milk in PBS (blocking solution) was added to each well and left for 1 hour at room temperature. This solution was then aspirated, and 100 μl of the human monoclonal antibody toTgase 1 (Bíomedical Technologies) diluted to 1/2000 in 1% milk in PBS was added to each well. The plates were incubated for 2 hours at 37 ° C. The solutions were then removed and the wells were washed 4 times with 1% milk / 0.05% Tween in PBS. Anti-mouse Fab 'conjugated with horseradish peroxidase was diluted at 1: 4000 in 1% milk / 0.05% Tween / PBS, and 100 μ of this solution was added to each well and incubated for 2 hours at 37 ° C. The solutions were then aspirated, then washed 3 times with 1% milk / 0.05% Tween in PBS. A substrate solution was prepared by dissolving 2 mg of O-phenylepodiamine (Sigma) in 5 ml of citrate pH buffer and 1.65 μl of H20 was added at 30%, 100 μl of this substrate solution was added to each well and were incubated in the dark for 5 minutes The reaction was stopped by adding 50 μl of 4 N H2SO4 The absorbance was measured at 490 nm (b) The keratinocyte differentiation was expressed as absorbance of transglutaminase (b) / μg AD? (a) The results obtained in the two separate experiments are summarized in Tables 9A and 9B.

Table 9A * p < 0.05 Table 9B * p < 0.05 The results in Tables 9A and 9B show that a combination of lactic acid and dextran (either 10 KD or 464 KD) significantly increased keratinocyte differentiation while the combination with arabinogalactan did not.

EXAMPLE 10 This example investigated the effect of dextran on the anti-aging efficacy of glycolic acid skin.

Procedure: The study was a 12-week bilateral comparison use test of two formulations. It was required that they come to the laboratory subjects for a pre-classification visit to determine if they had a moderate grade of photo-damaged skin on both forearms. Qualified subjects were required to make 6 additional visits over a period of 12 weeks. A visual evaluation was conducted at the baseline (week 0), week 4, 8 and 12 The product allocation was randomized and balanced for left / right use through the combination of subjects. Subjects were asked to use the appropriate product in the left / right arms at home and to apply approximately 1 g 2 times a day for 12 weeks. A minimum of 15 subjects qualified by comparison in pairs completed the study. Chemical (visual) determinations were conducted for photo-damaged skin (crepe / wrinkled or curly) using the following 10-point scale: 0 = none 1 -3 = mild 4-6 = moderate 7-9 = severe following pairwise comparisons. Comparison I in pairs: formulation of base A against formulation of base B + 85 of glycolic acid. Comparison II: base formulation A + 8% glycol against base formulation A + 8% glycolic + 5% dextran 10 KD. The Wilcoxon rank-range test, Pratt-Lehmann version, was used to statistically determine the average change in the base-line attributable to the treatment with the subject acting as a block in this analysis. In addition, to compare the degree of change of the baseline between doe treatments within a cell, the Wilcoxon non-paramétpca assigned range test was also used, Pratl-Lehmann version The results that were obtained are summarized in Tables 10A and 10B.

Table 10A Average improvement in photo-damaged skin (8% glycolic against base) *: 8% glycolic significantly provided a better? significantly higher on base (p <0.05) Table 10B Average improvement in photo-damaged skin (8% glycolic against 8% glycolic + 5% dextran 10 KD) ': 8% glycolic + 5% dextran provided a significantly greater improvement over 8% glycolic (p = 0.059) EXAMPLE 11 This example measured the effect of maltodextrin (Maltrin®) 180 glycolic acid itching at a pH of 3.8 in the base formula A, the in vivo itch test and the base A formula are described in Example 1.

Table 11 A Prognosis of itching / burning p < 0.1 Table 11 B Forced selection for itching / burning What side is worse? Results immediately, 2.5, 5.0 and 7.5 minutes after the application P < 0.1 Table 11C Prognosis of itching / burn p < 0.1 It can be seen from the results in Tables 11A and 11B that maltodextrin significantly reduced the itch / burn propensity of the base A formula containing 8% glycolic acid. The results in Table 11C show that the formulation containing maltodextrin was less itchy than the base A formulation.

EXAMPLE 12 Example 12 illustrates topical compositions according to the present invention. The compositions can be processed in a conventional manner. They are suitable for cosmetic use. In particular, the compositions are suitable for application on aged foot and / or damaged by UV rays to improve the appearance and feel thereof, as well as for the application to healthy skin to prevent or delay the deterioration thereof. A typical oil-in-water emulsion within the scope of the invention is as follows: Chemical name% / F 'that Dextran 10 KD 4 Glycolic acid 7 Propylene glycol 1 Glycerin 1 Hydroxyethyl cellulose 0. 5 Magnesium-aluminum silicate 0. 5 Imidazolidinyl urea 0. 5 Tetrasodium EDT 0. 05 Petrolatum 2 Isopropyl palmitate 5 Dimethicone 0 5 Cholesterol 0. 5 Cetyl alcohol 0. 5 Isostearic acid 3 Peg-40 stearate 1 Peg-100 stearate 1 Sorbitan stearate 1 Ammonium hydroxide P a pH 4 .0 Water DI cs. for 100% Another typical oil-in-water emulsion within the scope of the invention is as follows: Chemical name% / P 'that Maltodextrin 5 Glycolic acid 10 Polyethylene glycol 1 Hydroxyethyl cellulose 0. 5 Magnesium-aluminum silicate 0. 5 Imidazolidinyl urea 0. 2 Petrolate 2 Isopropyl palmitate 5 Dimethicone 0. 5 Cholesterol 0. 5 Stearic acid 3 Isostearic acid 1. .5 Glycerol stearate 1 5 Peg-40 stearate 1 Peg-100 stearate 1 Sorbitan stearate 1 Ammonium hydroxide P a pH 3 .8 DI water c. .s. for 100% A typical water-in-oil dispersion within the scope of the invention is as follows: Chemical Name% / Weight Neosinntane isostearyl 20 Capryl / capric glycerides from peg-8 6 Cetyl octanoate 17 Polyglyceryl-6-dioleate 15 Cyclomethicone 20 Glyceryl isostearate 0.5 Isostearic acid 0.5 Ceramide III 0.1 ppg-5-cetheth-20 3 Acid L -lactic / potassium lactate 6 Hydroxycaprilic acid 0.1 Water DI 1.3 Dextran 100 KD 10 The following oil-in-water emulsion within the scope d < the present invention was prepared: Chemical name% / F 'that Xanthan gum 0. 2 Disodium EDT 0. 1 PCA sodium 0. 5 Diazodinyl urea 0. 3 Titanium dioxide 1 Stearic acid 3 Cyclomethicone 0.3 Cetyl alcohol 0.5 Glyceryl stearate 0.5 Peg-100 stearate 0.5 Steareth-2 0.2 Lecithin 0.5 Tocopherol 0.2 Octyl methoxycinnamate 6 Dextran 10 K 6 Glycolic acid 3 Malic acid 2 Lactic acid 2 Triethanolamine for pH 3.8 Water DI is. for 100% It should be understood that the specific forms of invention illustrated here and described are intended to be representative only. Changes can be made, including, but not limited to, those suggested in this specification in the illustrated modes without departing from the obvious teachings of the description. Accordingly, reference should be made to the following appended claims to determine the full scope of the invention.

Claims (6)

1. - A cosmetic composition for the skin comprising (i) from 0.5 to 20% by weight of the composition of a dextran (ii) from 0.01 to 12% by weight of the composition of a weak carboxylic acid having a pKa value approximately 5% by weight. above 2; and (iii) a cosmetically acceptable vehicle.

2. A cosmetic composition for the skin comprising (i) from 0.5 to 20% by weight of the composition of a maltodextrin; (ii) from 2 to 20% by weight of the composition of a weak carboxylic acid having a pKa approximately above 2, and (Ii) a cosmetically acceptable vehicle.

3. The composition according to claim 1 or claim 2, wherein the composition is an oil-in-water emulsion.

4. The composition according to any of the preceding claims, wherein the pH of the composition is in the range of 3 to 6. 5.- A cosmetic method to treat aged skin, photo aged, dry, lined, or wrinkled , the method comprises applying to the skin the composition of any of claims 1-4. 6. A cosmetic method for reducing irritation or itching of the skin, the method comprises topically applying 0.5 to 20% by weight of the composition of a dextran or maltodextrin in a cosmetically acceptable vehicle.