Active ingredient combinations of 4-hydroxyacetophenone and one or more cinnamic acid derivatives

Abstract

Sunscreen-effective active ingredient combinations made up of (a) one or more cinnamic acid derivatives of formula (1a) and (1b) in which the groups X, Y and R can be chosen independently from the group hydrogen, and branched or unbranched C1-C 18 Alkyl, and (b) 4-Hydroxyacetophenone.

Description

AREA OF INVENTION

[0001] The present invention relates to combinations of active ingredients consisting of 4-hydroxyacetophenone and one or more cinnamic acid derivatives, as well as cosmetic or dermatological preparations containing these combinations of active ingredients. TECHNOLOGICAL BACKGROUND

[0002] The present invention relates to cosmetic or dermatological preparations containing active ingredients for the care and protection of the skin, in particular sensitive skin, and especially skin aged or aging due to intrinsic and / or extrinsic factors, as well as the use of such active ingredients and combinations of such active ingredients in the field of cosmetic and dermatological skin care.

[0003] Cosmetic skincare primarily means strengthening or restoring the skin's natural function as a barrier against environmental influences (e.g., dirt, chemicals, microorganisms) and against the loss of the body's own substances (e.g., water, natural fats, electrolytes).

[0004] If this function is disrupted, it can lead to increased absorption of toxic or allergenic substances or to infestation by microorganisms, resulting in toxic or allergic skin reactions.

[0005] In older skin, for example, regenerative renewal slows down, with the stratum corneum's ability to retain water particularly declining. As a result, it becomes inflexible, dry, and cracked ("physiologically" dry skin). This leads to barrier damage. The skin becomes susceptible to negative environmental influences such as the invasion of microorganisms, toxins, and allergens. Consequently, toxic or allergic skin reactions can even occur.

[0006] Pathologically dry and sensitive skin is characterized by a priori barrier damage. Epidermal intercellular lipids are produced incorrectly or in insufficient quantity or composition. The consequence is increased permeability of the stratum corneum and inadequate protection of the skin against the loss of hygroscopic substances and water.

[0007] The barrier function of the skin can be quantified by determining transepidermal water loss (TEWL). This refers to the evaporation of water from the body's interior, excluding water loss through perspiration. Determining the TEWL value has proven to be exceptionally informative and can be used to diagnose cracked or chapped skin, to assess the compatibility of chemically diverse surfactants, and for other purposes.

[0008] The water content in the outermost layer of skin is of utmost importance for its beauty and health. It can be positively influenced to a limited extent by introducing moisturizing agents.

[0009] Anionic surfactants, which are generally components of cleansing products, can cause a prolonged increase in the pH value of the stratum corneum, severely hindering regenerative processes that restore and renew the skin's barrier function. In this case, a new, often very unfavorable equilibrium is established in the stratum corneum between regeneration and the loss of essential substances through regular extraction, significantly impairing the skin's appearance and the physiological function of the stratum corneum.

[0010] Even a simple bath without added surfactants initially causes the stratum corneum of the skin to swell, the degree of which depends, for example, on the duration of the bath and its temperature. At the same time, water-soluble substances, such as water-soluble dirt particles, as well as the skin's own substances responsible for the stratum corneum's water-binding capacity, are washed away. Skin's own surface-active substances also dissolve and wash away a certain amount of skin lipids. This leads to a significant subsequent drying of the skin after the initial swelling, a process that can be further intensified by the addition of cleansing agents.

[0011] In healthy skin, these processes are generally insignificant, as the skin's protective mechanisms can easily compensate for such minor disturbances in the upper layers. However, even in the case of non-pathological deviations from the norm, such as those caused by environmental wear and tear or irritation, sun damage, aging skin, etc., the skin's surface protective mechanism is disrupted. In some cases, it may no longer be able to fulfill its function on its own and must be regenerated through external measures.

[0012] Furthermore, it is known that the lipid composition and quantity of the stratum corneum in pathologically altered, dry skin and in dry, but not diseased, skin of younger and older people deviates from the normal state found in healthy, normally hydrated skin of the same age group. The changes in the lipid pattern of the very dry, non-eczematous skin of patients with atopic eczema represent an extreme case of the deviations found in the dry skin of healthy individuals.

[0013] The effect of ointments and creams on the barrier function and hydration of the stratum corneum generally does not involve restoring or strengthening the physicochemical properties of the intercellular lipid lamellae. A significant contributing factor is simply the covering of the treated skin areas and the resulting water retention in the underlying stratum corneum. Co-applied hygroscopic substances bind the water, leading to a measurable increase in the water content of the stratum corneum. However, this purely physical barrier can be removed relatively easily. After discontinuing the product, the skin very quickly returns to its pre-treatment condition. Furthermore, the skincare effect can diminish with regular treatment, so that eventually the status quo is reached again, even during the course of treatment.With certain products, the skin's condition may temporarily worsen after discontinuation. Therefore, a lasting effect is generally not achieved, or only to a limited extent.

[0014] To support the natural regeneration of damaged skin and strengthen its physiological function, topical preparations increasingly contain intercellular lipid mixtures intended to help the skin rebuild its natural barrier. However, these lipids, especially ceramides, are very expensive raw materials. Furthermore, their effectiveness is often much less than hoped for.

[0015] Skin care within the meaning of the present invention primarily means that the natural function of the skin as a barrier against environmental influences (e.g. dirt, chemicals, microorganisms) and against the loss of endogenous substances (e.g. water, lipids, electrolytes) is strengthened or restored.

[0016] Products for the care, treatment, and cleansing of dry and stressed skin are generally well-known. However, their contribution to the regeneration of a physiologically intact, hydrated, and smooth stratum corneum is limited in scope and duration.

[0017] The effect of ointments and creams on the barrier function and hydration of the stratum corneum is essentially based on the covering (occlusion) of the treated skin areas. The ointment or cream, in effect, represents a (second) artificial barrier intended to prevent water loss from the skin. Consequently, this physical barrier can be easily removed—for example, with cleansing agents—thus restoring the original, impaired condition. Furthermore, the skin care effect can diminish with regular treatment. After discontinuing product use, the skin very quickly returns to its pre-treatment state. With certain products, the skin's condition may even temporarily worsen. Therefore, a lasting effect from the product is generally not achieved, or only to a limited extent.

[0018] The effect of some pharmaceutical preparations on the skin's barrier function even involves selective barrier damage, which is intended to allow active ingredients to penetrate the skin and enter the body. A disturbed appearance of the skin is sometimes accepted as a side effect.

[0019] The effect of nourishing cleansing products essentially lies in their efficient re-oiling with sebum-lipid-like substances. Simultaneously reducing the surfactant content of such preparations further limits damage to the stratum corneum barrier.

[0020] Antioxidants, preferably those used in skin-care cosmetic or dermatological preparations. In particular, the invention also relates to cosmetic and dermatological preparations containing such antioxidants. In a preferred embodiment, the present invention relates to cosmetic and dermatological preparations for the prophylaxis and treatment of skin aging, in particular skin aging caused by oxidative processes.

[0021] Antioxidants are substances that prevent oxidation processes, specifically the autoxidation of unsaturated compounds in fats. Examples of antioxidants used in cosmetics and pharmaceuticals include alpha-tocopherol, sesamol, bile acid derivatives, butylhydroxyanisole, and butylhydroxytoluene.

[0022] Antioxidants are primarily used as protective substances against the spoilage of the preparations containing them. However, it is also known that undesirable oxidation processes can occur in human and animal skin. Such processes play a significant role in skin aging.

[0023] The article “Skin Diseases Associated with Oxidative Injury” in “Oxidative Stress in Dermatology”, p. 323 et seq. (Marcel Decker Inc., New York, Basel, Hong Kong, editors: Jürgen Fuchs, Frankfurt, and Lester Packer, Berkeley / California) lists oxidative damage to the skin and its underlying causes.

[0024] UV radiation, for example, can lead to photo-oxidative reactions, whereby the photochemical reaction products then interfere with skin metabolism.

[0025] These photochemical reaction products are predominantly radical compounds, such as hydroxy radicals, hydroperoxy radicals, and superoxide ions. Undefined radical photoproducts that form within the skin itself can also exhibit uncontrolled subsequent reactions due to their high reactivity. Singlet oxygen, a non-radical excited state of the oxygen molecule, can also occur upon UV irradiation, as can short-lived epoxides and many others. Singlet oxygen, for example, is characterized by increased reactivity compared to the normally present triplet oxygen (radical ground state). However, excited, reactive (radical) triplet states of the oxygen molecule also exist.

[0026] To prevent such reactions, additional antioxidants and / or free radical scavengers can be incorporated into cosmetic or dermatological formulations.

[0027] In addition to UV radiation, other environmental pollutants such as ozone, cigarette smoke, oxidizing chemicals, metal ions (iron, nickel, copper, etc.), sulfur and nitrogen oxides also induce oxidative stress in the skin, thus promoting premature skin aging.

[0028] Exposure to heat can also lead to a significant increase in the lipid peroxide level of the affected skin, and even normal metabolic processes can induce oxidative stress.

[0029] Document US 2006 / 0110415 A1 discloses topical compositions containing esters of hydroxy acids, which serve as penetration or delivery agents for active pharmaceutical ingredients.

[0030] Document DE 10 2004 038 485 A1 concerns the use of certain new α-benzoyl cinnamic acid nitriles as UV filters (UV absorbers) in cosmetic and dermatological formulations such as sunscreens, day creams and hair care products.

[0031] Document JP H07 206645 A discloses a hair growth product whose active ingredients are acetophenone derivatives.

[0032] Document KR 10 20130134976 A refers to skin lightening compositions containing white rice extract and 4-hydroxyacetophenone. TASK OF INVENTION

[0033] The aim of the present invention was therefore to find ways to avoid the disadvantages of the prior art. In particular, the effect of the skin care products should be physiological, fast and lasting.

[0034] The specific objective of the present invention was to overcome the disadvantages of the prior art. In particular, an objective of the present invention was to provide active ingredients and products that act as antioxidants in vivo and / or counteract skin aging caused by oxidative stress. DESCRIPTION OF THE INVENTION

[0035] The present invention relates to light-protective active ingredient combinations consisting of (a) one or more cinnamic acid derivatives of formula (1a) and (1b) in which the groups X, Y and R can be chosen independently from the group hydrogen, and branched or unbranched C1-C 18 Alkyl, and (b) 4-Hydroxyacetophenone.

[0036] A well-known and highly effective antioxidant is 4-hydroxyacetophenone, which is marketed by companies such as Symrise under the trade name "Symsave". (R) H" is sold. It has the CAS number 99-93-4 and is characterized by the following chemical structure:

[0037] A disadvantage of this substance is that its solubility in cosmetic solvents such as oils or lipids is only moderate, which limits its use in cosmetic or dermatological preparations, which are mostly oil-based.

[0038] The object of the present invention was therefore to remedy this deficiency and to show ways in which the concentration of 4-hydroxyacetophenone used in dissolved form can be increased.

[0039] It was surprising and not foreseeable for the person skilled in the art that combinations of active ingredients consisting of one or more cinnamic acid derivatives and 4-hydroxyacetophenone, as well as cosmetic or dermatological preparations containing these combinations of active ingredients, would overcome the disadvantages of the prior art. Active ingredient combinations

[0040] The preferred cinnamic acid derivative is octyl methoxycinnamate (the 2-ethylhexyl p-methoxycinnamate or the 4-methoxycinnamic acid 2'ethylhexyl ester), which is marketed by DSM under the name Parsol, among others. (R) MCX is available and is characterized by the following structure:

[0041] The solubility tests were carried out at two different temperatures: at room temperature (approx. 20 °C) and at 35 °C.

[0042] The white, crystalline 4-hydroxyacetophenone was added slowly (over several hours) to the respective solvent in small portions while stirring until no further material could be dissolved. At this point, the solubility limit was reached. The amount of dissolved 4-hydroxyacetophenone was determined using an analytical balance. Undissolved material was clearly visible as a milky precipitate or individual crystals.

[0043] The experiments at 35 °C were conducted in a water bath. The temperature was kept constant by a temperature probe connected to the heating stirrer.

[0044] All experiments were carried out in screw-topped 15 ml glasses to prevent evaporation of the solvent.

[0045] Solubility was measured approximately 12-24 hours after the last addition of the substance, allowing the system to equilibrate. solvent Solubility of 4-hydroxyacetophenone at RT (approx. 20 °C) Solubility of 4-hydroxyacetophenone at 35 °C C12-15 Alkylbenzoate 2% (solved) - 2.25% (unsolved) 2.5-3.0 % Dicaprylyl ether 0.5% - 1.0% (unsolved) 1.0% (solved) - 1.5% (unsolved) 2-Ethylhexyl salicylate < 1 % 1 % Ethylhexyl methoxycinnamate at least 6% at least 7%

[0046] 4-Methoxycinnamic acid 2'-ethylhexyl ester dissolves 4-hydroxyacetophenone surprisingly much better than the well-known cosmetic oils dicaprylyl ether and alkyl benzoates.

[0047] Advantageously, weight ratios of the total amount of one or more cinnamic acid derivatives to the amount of 4-hydroxyacetophenone are selected from the range of 100 to 1 to 1 to 20, preferably from 50 to 1 to 1 to 10, and particularly preferably from 20 to 1 to 1 to 5.

[0048] Preferred concentrations of 4-hydroxyacetophenone used in cosmetic or dermatological preparations are selected from the range of 0.001% to 3%, preferably from 0.01% to 2%, and particularly preferably from 0.1% to 1%, in each case based on the total weight of the preparations.

[0049] The active ingredient combinations used according to the invention can be easily incorporated into common cosmetic or dermatological formulations, advantageously into pump sprays, aerosol sprays, creams, ointments, tinctures, lotions, nail care products (e.g. nail polishes, nail polish removers, nail balms) and the like.

[0050] It may also be advantageous to buffer the compositions according to the invention. A pH range of 3.5–8.0 is advantageous. It is particularly beneficial to select a pH value in the range of 4.5–7.5.

[0051] The cosmetic and / or dermatological formulations according to the invention can be composed in the usual way and used for the treatment of the skin and / or hair in the sense of a dermatological treatment or a treatment in the sense of skincare cosmetics. They can also be used in makeup products in decorative cosmetics. Cosmetic and / or dermatological formulations

[0052] For application, the cosmetic and / or dermatological formulations according to the invention are applied to the skin and / or hair in sufficient quantity in the manner customary for cosmetics and dermatological products.

[0053] Cosmetic and dermatological preparations in the form of sunscreens are advantageous. Ideally, these should also contain at least one UVA filter and / or at least one UVB filter and / or at least one inorganic pigment.

[0054] Cosmetic preparations according to the invention for protecting the skin from UV rays can be in various forms, such as those commonly used for this type of preparation. For example, they can be a solution, a water-in-oil (W / O) or oil-in-water (O / W) emulsion, a multiple emulsion (e.g., water-in-oil-in-water (W / O / W)), a gel, a hydrodispersion, a solid stick, or an aerosol.

[0055] The cosmetic preparations according to the invention may contain cosmetic excipients such as are commonly used in such preparations, e.g. preservatives, bactericides, antioxidants, perfumes, antifoaming agents, dyes, pigments with a coloring effect, thickeners, surfactants, emulsifiers, plasticizers, moisturizing and / or humectant substances, fats, oils, waxes or other usual components of a cosmetic formulation such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.

[0056] Emulsions are advantageous according to the invention and contain, for example, the aforementioned fats, oils, waxes and other fatty substances, as well as water and an emulsifier such as is commonly used for this type of formulation.

[0057] Gels according to the invention typically contain alcohols with a low carbon number, e.g. ethanol, isopropanol, 1,2-propanediol, glycerin and water or one of the aforementioned oils in the presence of a thickening agent, which in the case of oily-alcoholic gels is preferably silicon dioxide or an aluminum silicate, and in the case of aqueous-alcoholic or alcoholic gels is preferably a polyacrylate.

[0058] Solid sticks according to the invention contain, for example, natural or synthetic waxes, fatty alcohols, or fatty acid esters. Lip balm sticks and deodorizing sticks ("deo-sticks") are preferred.

[0059] Suitable propellants for cosmetic or dermatological preparations according to the invention, which can be sprayed from aerosol containers, are the usual known volatile, liquefied propellants, e.g. hydrocarbons (propane, butane, isobutane), which can be used alone or in mixtures. Compressed air is also advantageously usable.

[0060] Advantageously, the preparations according to the invention can also contain substances that absorb UV radiation in the UVB range, wherein the total amount of the filter substances is, for example, 0.1 wt. % to 30 wt. %, preferably 0.5 to 10 wt. %, in particular 1 to 6 wt. %, based on the total weight of the preparation, in order to provide cosmetic preparations that protect the skin from the entire range of ultraviolet radiation.

[0061] Cosmetic preparations for hair care include, for example, shampooing agents, preparations used when rinsing the hair before or after shampooing, before or after perming, before or after coloring or bleaching the hair, preparations for blow-drying or setting the hair, preparations for coloring or bleaching, styling and treatment lotions, hairspray, or perming agents.

[0062] The cosmetic preparations contain active ingredients and excipients such as are commonly used for this type of preparation for hair care and hair treatment.

[0063] Auxiliary substances include preservatives, surfactants, antifoaming agents, emulsifiers, thickeners, fats, oils, waxes, organic solvents, bactericides, perfumes, dyes or pigments whose purpose is to color the hair or the preparation itself, electrolytes, and preparations to prevent the hair from becoming greasy.

[0064] Cosmetic preparations that constitute a shampooing agent or a washing, showering or bathing preparation preferably contain at least one anionic, nonionic or amphoteric surfactant or mixtures thereof, at least one dialkyl-substituted carboxylic acid in the aqueous medium and auxiliary agents such as are commonly used for this purpose. EXAMPLES

[0065] The following examples are intended to illustrate the embodiments of the present inventions. All values ​​are given in wt.% unless otherwise stated. Example recipe 1 % by weight Cetylstearyl alcohol 3 Caprylic acid / capric acid triglycerides 3 Dicaprylyl carbonate 3 Dicaprylyl ether 2 Ethylhexyl methoxycinnamate 8 Butyl methoxydibenzoylmethane 1 Sodium stearoylglutamate 0,3 4-Hydroxyacetophenone 0,6 Acrylate / C10-30 Alkyl Acrylate Crosspolymer 0,4 Xanthan gum 0,2 Glycyrrhetic acid 0,1 Glycerin 5 Phenoxyethanol 0,6 Sodium hydroxide solution (pH adjusted to 6) qs Water 100% ad 100 Example recipe 2 % by weight Glyceryl stearate citrate 2 Glyceryl stearate 1 Stearyl alcohol 2 C12-15 Alkylbenzoate 4 Ethylhexyl methoxycinnamate 5 Ethylhexyl salicylate 3 Dimethicon 1 Phenylen-1,4-bis-(2-benzimidazyl)-3,3'-5,5'-tetrasulfonsaeure Dinatriumsalz (z. B.Neo Heliopan AP (R) ) 1 Carrageen 0,2 Carbomer 0,2 Methylparaben 0,2 4-Hydroxyacetophenone 0,3 Glycerin 5 Carnosine 0,1 Tapioca starch 1 EDTA 0,2 perfume 0,3 Sodium hydroxide solution (pH adjusted to 7) qs Water ad 100 Example recipe 3 % by weight Polyglyceryl-10 stearate 1 Glyceryl stearate 1 Cetyl alcohol 2 Ethylhexyl methoxycinnamate 6 2,4-Bis-{[4-(2-ethyl-hexyloxy)-2-hydroxy]-phenyl}-6-(4-methoxyphenyl)-1,3,5-triazin (Tinosorb (R) S) 2 Neutral fat 1 Jojoba oil 0,5 Octyldodecanol 4 Phenoxyethanol 0,6 polyacrylic acid 0,2 4-Hydroxyacetophenone 0,4 Hydroxypropylmethylcellulose 0,1 Glycerin 9 EDTA 0,1 Arctium lappa fruit extract (active ingredient: Arctiin) 0,3 Perfume 0,3 Vitamin A palmitate 0,05 Butylene glycol 3 Sodium hydroxide solution (pH adjusted to 5) qs Water ad 100 Example recipe 4 % by weight Polyglyceryl-3 methyl glucose distearate 2 Sorbitan stearate 2 Cetyl alcohol 2 C 12-15 Alkylbenzoat 2 Dicaprylyl ether 3 Caprylic acid / capric acid triglycerides 3 Butyl methoxydibenzoylmethane 2 Ethylhexyl methoxycinnamate 5 Dioctylbutamidotriazon (Uvasorb (R) HEB) 1 Dimethicon 2 4-Hydroxyacetophenone 0,2 Carrageen 0,1 Phenylbenzimidazole sulfonic acid 1 Acrylate / C10-30 Alkyl Acrylate Crosspolymer 0,3 Ubiquinone 0,02 Glycerin 6 EDTA 0,2 Magnesium ascorbyl phosphate 0,1 Ethylhexylglycerin 0,5 Sodium hydroxide solution (pH adjusted to 7) qs Water ad 100

Claims

[1] Light-protective active ingredient combinations made up of (a) one or more cinnamic acid derivatives of formula (1a) and (1b) in which the groups X, Y and R can be chosen independently from the group hydrogen, and branched or unbranched C1-C 18 Alkyl, and (b) 4-Hydroxyacetophenone. [2] Active ingredient combinations according to claim 1, characterized by , that 2-ethylhexyl p-methoxycinnamate and / or 4-methoxycinnamic acid 2'-ethylhexyl ester are used as cinnamic acid derivatives. [3] Combinations of active ingredients according to claim 1 or 2, wherein weight ratios of the total amount of one or more cinnamic acid derivatives to the amount of 4-hydroxyacetophenone are selected from the range of 100 to 1 to 1 to 20. [4] Active ingredient combinations according to claim 3, in which weight ratios of the total amount of one or more cinnamic acid derivatives to the amount of 4-hydroxyacetophenone are selected from the range of 50 to 1 to 1 to 10. [5] Active ingredient combinations according to claim 3, wherein weight ratios of the total amount of one or more cinnamic acid derivatives to the amount of 4-hydroxyacetophenone are selected from the range of 20 to 1 to 1 to 5. [6] Cosmetic or dermatological preparations containing combinations of active ingredients according to any of the preceding claims. [7] Preparations according to claim 4, in which 4-hydroxyacetophenone is present in weight concentrations selected from the range of 0.001% to 3%, in each case based on the total weight of the preparations. [8] Preparations according to claim 7, in which 4-hydroxyacetophenone is present in weight concentrations from the range of 0.01% to 2% based on the total weight of the preparations. [9] Preparations according to claim 7, in which 4-hydroxyacetophenone is present in weight concentrations from the range of 0.1% to 1% based on the total weight of the preparations.