MXPA99002838A - Metoxicinamiloxisalicilato and cosmetic compositions containing metoxycinamilosalicil - Google Patents

Abstract

Methoxycinnamyloxysalicylate (ferulyl salicylate) and a method of its preparation are described. Cosmetic skin conditioning compositions containing ferulyl salicylate are also disclosed. The compositions of the invention provide control of sebum secretion from sebocytes, improved oil control and improved skin feel, avoid shine and tack, and at the same time provide anti-aging benefits, resulting in an appearance Reduced wrinkles and aging skin, improved skin color, photo-aging skin treatment, an improvement in skin radiance, clarity and finish, and a healthy and youthful overall appearance of the skin

Description

I ^ ETOXICINAMILOXISALICILATO AND COSMETIC COMPOSITIONS CONTAINING ME OXICI AMYLOXISALICILATE FIELD OF INVENTION The invention relates to a novel compound, methoxycinnamyloxy alkylate, a method for its preparation and its use in cosmetic compositions.

ANTK (KL) ENTHUS OF THE INVENTION The compound of the present invention is a non-esterified salicylic acid compound in the ring, wherein the salicylic acid is attached via an ester linkage to ferulic acid. Ferulic acid is also known as methoxycinnamic acid. Several patents describe esters of salicylic acids. See, for example, US Pat. No. 2,116,347 (Grether et r.l.) And EP 0 ß "7 ^ 1 ^ fFow" Uclaf gel. "The esters described for most of the steres are alkyl esters of salicylic acid. Roussel Uclaf also mentions isopropylbenzyl salicylate, Neither Grether et al., Nor Roussel Uclaf describe the ester of the present invention.The esters of salicyloxycarboxylic acid of Grether differ in addition to the compound of the invention in at least that the compounds of Grether contain an ester group in place of a carboxy terminal group of the compounds of the invention Therefore, the Grether compounds contain two ester linkages, while the compounds of the invention contain only one ester linkage The compounds of the invention they can not be obtained by solely hydrolyzing the ester obtained by the Grether process, since the first ester bond would be hydrolyzed first to produce salicylic acid and acid. gone ferulico.Cosmetic products which improve the appearance of the skin every voice become more popular with consumers. Consumers often seek to alleviate or delay the signs of aging or photo-aging skin, such as fine lines and wrinkles, dry skin and drooping. Consumers often seek other benefits in addition to anti-aging. An undesirable skin condition, although frequent is an "oily skin" condition which results from an excessive amount of sebum on the skin. Sebum is the skin oil which is produced by the sebocytes (cells of the sebaceous glands in the skin) and then secreted to the surface of the skin. Oily skin is associated with a bright, undesirable appearance and an unpleasant feeling to the touch. Oily skin affects groups of different ages. The formation of free raiicales in the skin does not seem to be related to sebum secretion. Low concentrations of free radicals are formed in the skin as part of the natural metabolic pathways. The concentration of free radicals increases in response to UV radiation and other environmental oxidants, for example pollution and cigarette smoke. The increased concentration of free radicals leads to lipid peroxidation in skin cells and cell damage, which in turn results in premature aging of the skin with an accompanying loss of firmness and elasticity, wrinkles, discoloration, age spots and dryness . Antioxidants, such as vitamin E (alpha-tocopherol), decrease the concentration of free radicals in the skin. Cosmetic assets which provide more than one benefit are highly desirable, from the perspective of manufacturers as well as consumers. Especially valuable are compounds which are capable of providing more than two cosmetic benefits. PCT application WO93 / 10755 reports salicylic acid as an effective anti-wrinkle agent. Leveque et al., (US Pat. No. 5,262,407) report the use of certain acetylated salicylic acid derivatives in the ring as a treatment against skin aging. Salicylic acid rented in the ring has been reported in Japanese Patent 4036238 (Takasago Perfumery KK) for the treatment of acne vulgaris. E. Graf "Anti-oxidant Potential of Ferulic Acid," Free Radical Biology and Medicine, vol. 13, pp. 435-48, 1992 describes that ferulic acid can photoproterate the skin when using cosmetic lotions. Nothing in the prior art described above mentions the methoxycinnamyloxy alkylate included in the present invention. It has been found, as part of the present invention, that ferulic acid or salicylic acid, when used individually, does not significantly reduce sebum secretion, while the ferulyl salicylate used in the present invention obtains a significant reduction in the sebum secretion. In addition, the use of ferulyl salicylate is advantageous compared to the use of a physical mixture of salicylic acid and ferulic acid: ferulyl salicylate is easier to formulate with, since ferulic acid and salicylic acid individually carry a greater amount of incompatibilities compared to a single molecule of ferulyl sa cilate.

BRIEF DESCRIPTION OF THE INVENTION The present invention includes a compound of the formula I: and a process for making the novel compound. The present invention includes a skin conditioning composition comprising: (a) from 0.0001 to 20% by weight of methoxycinnamiloxal icylate of formula I: and (b) a cosmetically acceptable vehicle. The present invention also includes a method for controlling or preventing an oily skin condition, especially in the facial area, by applying to the skin a composition comprising methoxycinnamyloxy alkylate in a cosmetically acceptable vehicle. The invention also includes a cosmetic method for reducing, preventing, or controlling sebum secretion from sebocytes by applying the composition of the invention to the skin. The invention also includes a cosmetic method for stimulating the synthesis of collagen and glycosaminoglycan by fibroblasts in the skin, by applying the composition of the invention to the skin. The invention also includes a cosmetic method for protecting the skin from free radical activity (i.e., releasing oxidative stress in the skin) by applying the composition of the invention to the skin. The invention also includes a cosmetic method for treating or delaying a chronoenvej skin < = day, photo-aged, dry, wrinkled or with ripples, =? 1 protect the skin from harmful light UVA and UVB (sunscreen) which increases the firmness and flexibility of the stratum corneal, and generally increases the quality of the skin applying the composition of the invention to the skin. The methods and compositions of the invention provide control of sebum secretion from sebocytes, improved oil control and improved skin feel, avoid shine and tack, and at the same time provide antioxidant and anti-aging benefits which result in a reduced appearance of freckles and aged skin, an improved color of the skin, the treatment of photo-aged skin, an improvement in the radiance of the skin and clarity and finish, and a healthy and youthful overall appearance of the skin.

DETAILED DESCRIPTION OF THE INVENTION Except in the operating and comparative examples, or where otherwise explicitly stated, all quantities in the description indicate material quantities, proportions or reaction conditions physical properties of materials and / or use that is understood as modified by the word "approximately". All amounts are by weight, unless otherwise specified. The terms "methoxycin oxysilocylate" and "ferulyl salicylate" are used interchangeably herein. The term "skin" as used herein includes the skin of the face, neck, chest, back, arms, hands and scalp. The compound according to the present invention has the general formula I: The process of the invention for making the compound of formula I includes at least two steps: (a) preparing a hilide of salicylic acid by reacting salicylic acid with thionyl halide or oxalyl halide; and (b) reacting the salicylic acid halide with ferulic acid, to obtain the compound of the invention of formula I. In the first step, salicylic acid is mixed with thionyl halide (or oxalyl), more preferably chloride, ( molar in the general range from 1: 1 to 2: 1) in an anhydrous, typically non-polar solvent, in the presence of pyridine catalyst at a temperature of 20 to 45 ° C for 0.5-2 hours. At the end of this reaction, salicylic acid chloride is obtained. Optionally, the solvent is distilled at least partially. Subsequently ferulic acid is dissolved in a dry solvent (for example dry acetone, toluene, THF) and pyridine is added to this solution < 1 equivalent per 1 equivalent of salicylic acid halide). The salicylic acid chloride is added dropwise, with agitation, to this solution. The molar ratio of salicylic acid chloride to ferulic acid is typically in the range from 1: 1 to 1: 2. Typically, the reaction is carried out at 40-45 ° C for several hours, before heating to reflux for 3 hours, and completion is monitored by CCD. Subsequently, the solvent is removed and the product is isolated by extraction and purified by column chromatography and recrystallization. The product is a white powder. The methoxycinnamyloxy salicylate is incorporated in the compositions of the invention in an amount from 0.0001 to 20%, preferably in order to maximize the benefits at a minimum cost, in an amount from 0.01 to 12%, and more preferably from 0.1 up to 8% COSMETICALLY ACCEPTABLE VEHICLE _ The composition according to the invention also comprises a cosmetically acceptable vehicle to act as a diluent, dispersant or carrier for methoxycinnamyloxy salicylate in the composition, so that its distribution is facilitated when the composition is applied to the skin. Vehicles other than, or in addition to water, may include emollients, solvents, wetting agents, liquid or solid thickeners and powders. An especially preferred non-aqueous carrier is a polydimethylsiloxane and / or a polydimethylphenylsiloxane. The silicones of this invention can be those with viscosities ranging anywhere from about 10 to 10,000,000 mm2 / s (centistokes) at 25 ° C. Mixtures of low and high viscosity silicones are especially desirable. These silicones are available from General Electric Company under the trademarks Vicasil, SE and SF and from the Dow Corning Company under the series 200 and 550. The amounts of silicone which can be used in the compositions of this invention vary anywhere from % up to 95%, preferably from 25% to 90% by weight of the composition. The cosmetically acceptable vehicle will usually constitute from 5% to 99.9%, preferably from 25% to 80% by weight of the composition, and, in the absence of other cosmetic adjuvants, it can form the remainder of the composition. Preferably, the vehicle is at least 80% by weight of water, by weight of the vehicle. Preferably, the amount of water is at least 50% by weight of the composition of the invention, more preferably from 60 to 80% by weight, by the weight of the composition. Preferred compositions are oil-in-water emulsions containing at least 60%, and preferably at least 80%, water.

COSMETIC MATERIALS AND ADJUVANTS BENEFICIAL FOR THE SKIN. OPTIONAL Although methoxycinnamyloxy alkylate has a functionality as a sunscreen (because it is a salicylate derivative), the compositions of the invention preferably include additional sunscreens to further decrease the exposure of the skin to harmful UV rays. Sunscreens include those materials commonly used to block ultraviolet light. Illustrative compounds are PABA derivatives, cinnamate and salicylate derivatives (other than ferulyl salicylate). For example, octyl methoxycinnamate and 2-hydroxy-4-methoxybenzophenone, also known as oxybenzone, may be used). Octyl methoxycinnamate and 2-hydroxy-4-methoxybenzophenone are commercially available under the trademarks, Parsol MCX and Benzophenone-3, respectively. The exact amount of sunscreen used in the emulsions can vary based on the desired degree of protection of the sun's UV radiation. An oil or oily material may be present, together with an emollient to provide either a water-in-oil emulsion or an oil-in-water emulsion, depending primarily on the average hydrophilic / lipophilic balance (HLB) of the emollient used. The concentrations of such emollients can vary from about 0.5% to about 50%, preferably between about 5% and 30% by weight of the total composition. Emollients can be classified under such general chemical categories as esters, fatty acids and alcohols, polyols and hydrocarbons. The esters can be mono- or di-esters. Acceptable examples of diesters-fatty acids include dibutyl adipate, diethyl sebacate, diisopropyl dimerate and dioctyl succinate. Acceptable branched chain fatty esters include 2-ethylhexyl myristate, isopropyl stearate and isostearyl palmitate. Acceptable tribasic acid esters include triisopropyl trilinoleate and trilauryl citrate. Acceptable straight chain fatty esters include lauryl palmitate, myristyl lactate, oleyl eurcate and stearyl oleate. Preferred esters include cococaprylate / caprate (a mixture of coco-caprylate and coco-caprate), propylene glycol myristyl ether acetate, diisopropyl adipate and cetyl octanoate. Suitable fatty alcohols and acids include those compounds having from 10 to 20 carbon atoms. Especially preferred are compounds such as cetyl, myristyl, palmitic and stearyl alcohols and acids. Among the polyols which can serve as emollients are the polyhydroxyl alkyl chain and branched chain compounds. Polymeric polyols such as propylene glycol and polyethylene glycol may also be useful. Butylene and propylene glycol are also especially preferred as penetration enhancers. Exemplary hydrocarbons which can serve as emollients are those having hydrocarbon chains anywhere from 12 to 30 carbon atoms. Specific examples include mineral oil, petroleum jelly, squalene and isoparaffins. Another category of functional ingredients within the cosmetic compositions of the present invention are thickeners. A thickener will usually be present in amounts anywhere from 0.1 to 20% by weight, preferably from about 0.5% to 10% by weight of the composition. Exemplary thickeners are crosslinked polyacrylate materials available under the trademark Carbopol from B.F. Goodrich Company. Gums such as xanthan, carrageenan, gelatin, carayá, pectin and locust bean gum can be used. Under certain circumstances, the thickening function can be carried out by a material that also functions as a silicone or emollient. For example, silicone forms exceeding 10 centistokes and esters such as glycerol stearate have double functionality. Powders can be incorporated in the cosmetic composition of the invention. These powders include canvas, talc, kaolin, starch, smectite clays, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, octenyl aluminum starch succinate and mixtures thereof. Other minor adjuvant components can also be incorporated into the cosmetic compositions. These ingredients may include coloring agents, opacifiers and perfumes. The amounts of these minor adjuvant components can vary anywhere from 0.001% to 20% by weight of the composition.

USE, FORM AND PACKAGING OF THE PRODUCT In use, a small amount of the composition, for example from 1 to 100 ml, is applied to exposed areas of the skin, from a suitable container or applicator and, if necessary, then it is spreaded over and / or rubbed on. the skin using your hand or fingers or a suitable device. The cosmetic skin composition of the invention can be formulated as a lotion, cream or gel. The composition can be packaged in a suitable container to adapt its viscosity and its proposed use by the consumer. For example, a lotion or cream can be packaged in a bottle or a rotating ball applicator, or a propellant-driven aerosol device or a container with a pump suitable for operation by the fingers. -When the composition is a cream, it can simply be stored in a non-deformable bottle or a container that can be pressed, for example as a tube or bottle with lid. The composition can also be included in capsules such as those described in U.S. Patent 5,063,507 (anhydrous silicone-based composition within a gelatin capsule), incorporated herein by reference. Accordingly, the invention also provides a closed container containing a cosmetically acceptable composition, as defined herein. The following specific examples further illustrate the invention, but the invention is not limited thereto.

EXAMPLE 1 Methods and Materials Magnetic resonance spectra of the proton were recorded in a Bruker AC model 200 spectrophotometer. Chemical shifts are reported in parts per million from tetramethylsilane as an internal standard. The spin multiplicities are indicated as follows: s (singlet), d (doublet), t (triplet), c (quartet), m (multiplet) and a (broad). The deuterated NMR solvents contain 99.0-99.8 deuterium in the indicated position, and were purchased from Cambridge Isotopic Laboratories. Gas chromatography (GC) was performed using a Hewlett-Packard 5890 Series II gas chromatograph, with an HP 7673 injector controlled by the Hewlett-Packard ChemStation software. A Hewlett-Packard HP-1 25 M x 0.22 mm column with a 0.33 μm coating of cross-linked methylsilicone was used. The parameters were as follows: Injection temperature = 290 ° C, determination temperature = 290 ° C, initial temperature dl = 50 ° C, initial time = 5 minutes, speed = 25 ° C / 'min, final oven temperature = 290 ° C. The samples were analyzed as ethers / trimethylsilyl esters. Gas chromatography / mass spectrometry was performed on a Hewlett-Packard 5890 Series II gas chromatograph together with a Finnigan MAT ITD 800 ion trap detector. The 25 M x 0.32 mm HP-5 column has a coating of 0.52 μm of 5% crosslinked phenylmethylsilicone. The differential scanning calorimetry experiments were carried out on a Dupont DSC equipment with a cell base 2910 and a thermal analyzer 2100. The samples of approximately 1 mg were accurately weighed on aluminum trays which were then hermetically sealed. After equilibration at 30 ° C, the samples were heated at a rate of 5 ° C / minute.

All solvents were reactive grades and were used as received. Reagents were purchased from Aldrich or Sigma Chemical companies and used as received.

Stage 1 : In a clean, dry 250 ml round bottom flask, 5.0 g (36 mmol) of salicylic acid, 100 ml of anhydrous toluene and 4-5 drops of pyridine catalyst were charged. The flask was equipped with a stir bar, an addition funnel and a nitrogen sparger. 4.7 g (40 mmoles) of thionyl chloride in 20-25 ml of anhydrous toluene were charged into the addition funnel. The thionyl chloride solution was added to the reaction flask dropwise under ambient conditions. When the addition was complete, the reaction was stirred at 40-45 ° C for several hours before any excess thionyl chloride and part of the toluene was removed under vacuum.Thirst.

Stage 2 : In a clean, dry, 500 ml round bottom flask, 7.0 g (36 mmol) of ferulic acid, 200 ml of anhydrous toluene and 3.4 g (40 mmol) of pyridine were charged. With stirring, an addition funnel and a nitrogen sparger, the salisyl chloride solution was added into the addition funnel.The salicyloyl chloride solution was added to the reaction flask dropwise under ambient conditions. the reaction was stirred at 40-45 ° C for several hours before heating to reflux for 3 hours before the heat was removed and the reaction was continued stirring under ambient conditions overnight The reaction mixture was filtered under vacuum to Remove the brown precipitate formed during the reaction The toluene filtrate is concentrated under vacuum to provide 5.2 g of a yellow solid which is 52% of methoxycinnamyloxy salicylate, by gas chromatography and by Gas chromatography / mass spectrometry. 2.4 g of the product was purified by silica gel column chromatography to provide 600 mg of pure methoxycinnamyloxy alkylate (also known as ferulyl salicylate) as a white fine powder. l NMR (200 MHz, CdCl 3): d 8.0 (d, 1H); 7.6 (m, 2H), 7.0 (m, 2H), 6.5 (d, 1H), 3.9 (s, 3H) CG (retention time) 15.9 minutes DSC: access temperature (° C): 192 m / z (GC / MS): 531 [M + H] .'JxTM.c Example 2 This example measures the production of procollagen I by fibroblasts in response to treatment with ferulyl salicylate ("FS"). Collagen is a predominant protein in the skin. Its synthesis decreases with aging or photodamage. The degradation or restriction of collagen increases the tensile strength of the skin, which causes wrinkles and laxity. Many studies involving human subjects have shown that type I collagen decreases with increasing severity of photodamage (see Kligman, A., JAMA, (1969), 210, pp. 2377-2380; Lavker, R., J. Inv. Derm., (1979), 73, 79-66, Smith J. et al., J. Inv. Derm., (1962), 39, pp. 347-350, and Shuster, S. et al., Br. J. Dermatol., (1975), 93, pp. 639-643); and a certain correlation has been reported in the histology of wrinkles and the reduction in collagen concentrations in skin expoto the sun. See Chen., S .; Kiss, I., J. Inv. Derm., (1992), 98, pp. 248-254. Voorhees and colleagues have supported these findings by demonstrating the restoration of photodamaged human skin with type I collagen by topical treatment with tretinoin. See Christopher, E., et al., The New Eng. Jou. of Medicine (1993), 329, pp. 535. Procollagen I is a precursor of collagen. The increaproduction of procollagen I in response to the application of a test compound is an indicator of an increaconcentration of collagen.

Procollagen I staining protocol for slot transfer (Slot Blot) Neonatal human dermal fibroblasts are acquired from Clonetics Corp., San Diego CA. All cell culture materials were purchafrom Life Technologies, NY and uin passages 5-10. Cells were seeded at a density of approximately 10,000 / well in 48 inner wells of a 96-well plate in medium containing DMEM (Dulbecco's modified Eagle's medium) high glucose supplemented with 2 mM L-glutamine, 10% serum Fetal bovine and antibiotic and antifungal solutions. The 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 dowith 200 μl of a solution of a test compound in serum free DMEM. Each dosage was doubled in a total of six wells. The test compounds were uat concentrations indicated in Table 1 below. The control did not contain a test compound. After 24 hours, the solution of the test compound or the control solution was removed and the cells were re-dowith 100 μl of a solution of a test compound in serum-free DMEM. The test compounds were uat concentrations indicated in Table 1 below. After 24 hours, the solution of the test compound or the control solution was stirred and stored over the weekend at 4 ° C with protease inhibitor (Sigma aprotinin) in an aprotinin to medium ratio of 1: 200. Subsequently, the solution of the test compound in DMEM was diluted (approximately 20 μl of sample in 200 μl of DMEM). The nitrocellulose membrane and 3 sheets of filter paper were moistened in buffered saline with Tris (TBS, pH 7.3). A slot transfer apparatus (BioRad Labs, CA) was fitted with 3 sheets of filter paper at the bottom, a membrane at the top and tightened tightly. 100 ml of TBS was added per well. Vacuum was used to suck TBS through the membrane. The solution of the test compound or control was vortexed, then 100 μl was charged per well and filtered by gravity. The procollagen from the test solution was bound to the membrane at this point in the procedure. The membrane was removed from the apparatus, the excess was trimmed and a mark was made in the lower right corner for orientation. The membrane was placed in blocking solution (5% milk powder in Dulbecco's phosphate buffered saline) overnight at 4 ° C, with shaking. Subsequently the membrane was incubated for 1.5 h at room temperature with 1. 5 ml of rat antibody against the terminal amino part of human procollagen (Chemicon MAB1912) in TBS with 0.1% BSA (ratio of antibody to buffer / BSA of 1: 100) in a sealed bag, with shaking. Subsequently, the membrane was removed; Washed 3 times for 5 minutes in TBS / 0.1% Tween. The membrane was then incubated for 1 hour at room temperature in 2 ml of anti-rat antibody, conjugated with peroxidase, biotinylated (Vector Labs) in TBS with 0.1% BSA (ratio of antibody to buffer / BSA of 1: 1000) in a sealed bag, with agitation. The membrane was washed 3 times for 5 minutes in TBS / 0.1% Tween, 3 ml of PBS were incubated with 30 μl each of solutions A and B of the Vectastain equipment for 30 minutes. The membrane was placed in the resulting solution for 30 minutes in a sealed bag, with shaking. Subsequently the membrane was removed and washed twice for 5 minutes with TBS / 0.1% Tween. The membrane was then stained using the following solution. : 12. 5 mg of 3-amino-9-ethylcarbazole (Sigma) 3,125 ml (approximately) of DMF (N, -dimethylformamide, from Sigma) 21.5 ml of 0.2M NaOAc buffer, pH 5.2 12.5 μl of H202.

The membrane was stained until color developed and the reaction was stopped with 2 washes for 10 minutes of running water. The spot was scanned on a BioRad GS700 image analysis densitometer. The times of increase were calculated as a proportion of the densitometer readings for cells treated with a test compound, over the control. The results that were obtained are summarized in table 1.

TABLE 1 It can be seen from the data in Table 1 that the addition of ferulyl salicylate at various concentrations to fibroblast cultures results in increased production of procollagen I, as indicated by the higher densitometer readings compared to the control. - - Example 3 This example measures the production of glycosaminoglycans by fibroblasts in response to treatment with various test compounds. Glycosaminoglycans (GAGs) are a family of polysaccharides which (with the exception of hyaluronic acid (HA)) can bind to a protein core, forming a proteoglycan. The main GAGs of the dermis are HA and dermatan sulfate, with small amounts of chondroitin-4-sulfate and chondroitin-6-sulfate present. Elaborated as much by the keratinocitos as by the dermal fibroblasts, the GAG are essential components of the extracellular matrix, although they constitute only 0.2% of the dry weight of the skin. GAGs are hydrated in the skin (HA can retain up to lOOOx its mass in water) and maintain the integrity of the basement membrane, regulate cell interactions and nutrient transport, and are involved in the formation of collagen and possibly elastic fiber . It has been shown that the proportion of GAGs (especially HA) in the dermis decreases with age. See Perlish et al, "THe Role of Glycosaminoglycans in Aging of the Skin." It has been shown that retinoic acid, the anti-aging active that represents the reference point, has been shown to increase the GAG content of the spiny and granular layers of the epidermis and the papillary dermis of aged skin in vivo. See Kligman et al., "Effects of topical tretinoin on non-sun-exposed protected skin of the elderly" - J. Am Acad Dermatol 1993: 29: 25-33.

Protocol for measuring GAGs Neonatal human dermal fibroblasts were purchased from Clonetics Corp., San Diego CA and used in the 5-10 passages. All materials for cell culture were purchased from Life Technologies, NY. Cells were seeded at a density of approximately 50,000 / well in a 12-well plate in a medium containing DMEM (Dulbecca-modified Eagle's medium), high glucose supplemented with 2 mM L-glutamine, 10% fetal bovine serum and antibiotic and antifungal solutions. The cells were then grown to confluence for 2 days. At the confluence, each well was moistened in serum-free DMEM and the cells were dosed with the test compounds (in triplicate) in 750 μl of serum-free DMEM. The test compounds were used at a concentration indicated in Table 2 below. The controls did not contain any test compounds. After 24 hours, this medium was aspirated and the treatment step was repeated. After a second 24-hour period, this medium, which contains the soluble GAGs, was collected and frozen until analysis. A Zeta Probe membrane positively charged in sterile water was moistened and placed in a Dot-Blot apparatus (both from Bio-Rad Labs, Hercules, CA). It was applied to each well 100 μl of water and extracted through it, using vacuum. After reheating, 100 μl of test sample or standard samples (hyaluronic acid or bovine trachea chondroitin sulfate Sigma, St. Louis, MO) were applied to the membrane and allowed to filter by gravity (approximately 1.5-2 hours). The GAGs are now attached to the membrane. The membrane was blocked with 3% w / v fatty acid-free bovine serum albumin (Sigma) in water for 1 hour. A coloring solution of 0.5 p / v Alcian dye is made Blue (ICN Biochemicals, Cleveland, OH) in 3% acetic acid, pH approximately 2.3. The membrane is washed twice in distilled water and then stained in the dye solution on a rotary shaker for 15 minutes. The dye is removed by pouring and the membrane is stained twice for 15 minutes each time in 3% acetic acid. The membrane is moistened in water and left to dry overnight. The Bio-Rad GS 700 image analysis densitometer is used to quantify the color intensity at each point. The increase in multiples over the control was calculated as a proportion of the densitometer readings for cells treated with a test compound on the control. Table 2 summarizes the results that were obtained.

TABLE 2 It can be seen from the data in Table 2 that the addition of ferulyl salicylate at various concentrations to fibroblast cultures results in an increased production of GAGs, as indicated by higher readings on the densitometer compared to the control.

Example 4 This example reports an in vitro analysis of sebum suppression by various test compounds.

Sebocyte Lipogenesis Assay in vitro Human sebaceous glands were isolated from the nose of a male person (age 60) and cultured using submerged tissue culture techniques (Bajor et al.

J. Invest. Dermatol. 102: 1594, P. 564). These sebocytes accumulate droplets of intracellular lipids characteristic of mature human sebum. The ferulic and salicylic acids of Sigma were obtained. Sebocytes harvested and submitted to passage were added to each well of a 48-well tissue culture plate and incubated at 37 ° C in the presence of 7.5% C02 for 7 days. On the day of experimentation, the growth medium was removed and the sebocytes were washed three times with Dulbecco's modified Eagle's medium (DMEM, free of glucose, free of phenol red). The fresh DMEM in an amount of 0.5 ml was added to each well and 5 μl of a test agent, at final concentrations ranging from 1 micromolar to 1 millimolar. Wells were used in triplicate for each sample. The controls consisted of DMEM, ethanol (used to solubilize methoxycin oxysalicylate) and tridecylsalicylate, a positive control which decreased sebum production and which was used as a control to verify the integrity of the sebocyte assay. All cultures were incubated at 37 ° C / 7._5% C0¿ for 30 minutes. A radioactive label is prepared by adding 100 μl of acetic acid labeled with 1.1C (Amersham, sodium salt, specific activity of 56 mCi / mmol) to 10 ml of 25 mM sodium acetate buffer. Then 50 μl containing the sebocytes and the test agents were added to each well. The cultures were returned to the incubator for 4 hours. Subsequently, the sebocytes were moistened three times with buffered saline solution with fresh phosphate (PBS) to remove the active, unbound and radioactive label. The radioactive label remains in cultured sebocytes and is counted using a Beckman scintillation counter. The results are expressed as% reduction reduction compared to the control (ethanol). The higher the number, the better the result. Table 3 below summarizes the results that were obtained.

TABLE 3 EXPERIMENT 4 Ferulic acid 1 micromolar 2.7 6.8 0.545 10 micromolar 4.1 6.2 0.33 100 micromolar 8.6 8.6 0.009 It can be seen from the results in Table 3 that a concentration of 1 micromolar and higher ferulyl salicylate consistently suppresses the secretion of sebum by the sebocytes. Ferulic acid is only scarcely statistically effective at the highest concentration of 100 micromolar. Salicylic acid is not effective.

EXAMPLE 5 This example reports a chemical assay of antioxidant activity of ferulyl salicylate. The chemical assay measures the antioxidant activity of ferulyl salicylate tested at a concentration of 1M solution. 2, 2'-azino-di- [3-ethylbenzothialoesulfonate] (6.1 μmol / 1) and methyoglobin (610 μmol / 1) are solubilized in phosphate-buffered saline (5 mmol / 1, pH 7.4). Subsequently, 20 μl of ferulyl salicylate was added and the absorbance was measured at 734 nm before and after the addition of the substrate, hydrogen peroxide (250 μmol / 1). The initial absorbance removes the absorbance contained in the substrate. This avoids discrepancies in the absorbance due to the test compound itself. The absorbance changes were examined with time, and therefore the multiple points in time. The results were expressed as% oxidation in relation to a control containing all the test components, but etanal instead of the test reagent (100% oxidation). A high number means that there is no oxidation prevention, or that it is a poor oxidant. The antioxidant activity of Trolox (registered trademark of Hof fman-LaRoche), a water-soluble form of vitamin E, was measured to establish the validity of the test. Trolox from Aldrich (2.5 mmol / l) was purchased. Oxidation was calculated by% of Trolox in relation to water (100% oxidation). The lower the oxidation values in%, the better the antioxidant. Table 4 summarizes the results that were obtained.

TABLE 4 It is evident from the results in Table 4 that ferulyl salicylate has excellent antioxidant activity, at both concentrations tested. The chemical assay outlined above measures the antioxidant activity obtained via direct extinction of free radicals, and not through the anti-inflammatory pathway. The trial establishes that ferulyl salicylate acts as an antioxidant via direct extinction of free radicals.

EXAMPLE 6 Example 6 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 to wrinkled, rough, scaly, aged and / or damaged skin by UV and / or oily skin to improve the appearance and feel d < = the same, as well as for application to healthy skin in order to avoid or delay the deterioration thereof.

OIL EMULSION IN WATER OIL EMULSION IN WATER EMULSION WATER IN OIL HIDROGEL SERUM ANHYDRO HYDRO-ALCOHOLIC GEL It can be understood that the specific forms of the invention illustrated and described herein are intended to be representative only. Changes may be made, including but not limited to those suggested in this specification, in the illustrated modalities without inartar of the clear teachings of the description. Accordingly, reference should be made to the following appended claims to determine the full scope of the invention.

Claims (8)

1. A compound of formula I
2. 2. A process for making a compound according to claim 1, characterized in that the process comprises the steps of: (a) preparing a salicylic acid halide by reacting salicylic acid with thionyl halide or oxalyl halide; and (b) reacting the salicylic acid halide with ferulic acid to obtain the compound of the invention of formula I.
3. 3. A skin conditioning composition, characterized in that it comprises: (a) from 0.0001 to 20% by weight of methoxycinnamyloxy alkylate of formula I and (b) a cosmetically acceptable vehicle
4. 4. A method for controlling an oily skin, the method is characterized in that it comprises applying to the skin the composition according to the claim.
5. 5. A method for reducing or controlling the sebum secretion of sebocytes in the skin, the method is characterized in that it comprises applying to the skin the composition according to claim 3.
6. 6. A method for stimulating the synthesis of collagen and glycosamylaminoglycan by fibroblasts in the skin, the method is characterized in that it comprises applying to the skin the composition according to claim 3.
7. 7. A method for treating aged, photo-aged, dry, wrinkled or creased skin, the method is characterized in that it comprises applying to the skin the composition according to claim 3.
8. 8. A method for protecting the skin from harmful UVA and UVB light, the method is characterized in that it comprises applying to the skin the composition according to claim 3.