WO2008040303A1

WO2008040303A1 - Dermatological preparation containing hydrated phosphatidylcholine

Info

Publication number: WO2008040303A1
Application number: PCT/DE2007/001699
Authority: WO
Inventors: Eckart Voss; Rolf-Dieter Schilling
Original assignee: Maxim Markenprodukte Gmbh & Co. Kg
Priority date: 2006-09-26
Filing date: 2007-09-20
Publication date: 2008-04-10
Also published as: EP2088990A1

Abstract

Topical dermatological preparation, wherein the active compounds are present as saturated concentrate in the multilamellar layers of hydrated phosphatidylcholine. The invention can be used in cosmetics and medicine.

Description

DERMATOLOGICAL PREPARATIONS CONTAINED HYDROGENATED PHOSPHATIDYLCHOLINES

The invention relates to topical dermatological preparations for applications in cosmetics and medicine in which the active ingredients are present as a saturated concentrate in the multilamellar layers of hydrogenated phosphatidylcholines (PC), a process for their preparation and their use.

Cosmetic preparations are according to the European Cosmetics Regulation exclusively or predominantly intended to be applied externally to the body of man to z. B. cleaning, stabilizing, vitalizing and deodorizing u. a. to act on the skin, oral cavity, nails and hair.

Applications of dermatological preparations in medicine are aimed at the cure or improvement of diseased skin conditions.

The usual dermatological preparations for applications in cosmetics and medicine are usually a mixture of active ingredients and excipients, their mode of action as a single substance or as a mixture of substances, their absorption in the body, their rate of release, their place of release and the site of action often is uncertain. This may be tolerated in cosmetics with intact skin because of their high barrier and repair performance, but may cause the intended positive effect of the drug in its opposite with damaged skin.

Object of the present invention are new dermatological preparations in which the proportion of excipients in relation to the active ingredients is significantly reduced and undesirable effects are minimized. New topical dermatological preparations were found; containing

10 to 50% by weight of hydrogenated phosphatidylcholines and 0.5 to 50% by weight of an active ingredient, wherein the active ingredient in the multilamellar layers of the hydrogenated

Phosphatidylcholins is incorporated, and as additives water, solubilizers and cosmetic auxiliaries and supplements, wherein the sum of the ingredients 100 wt.% Results.

The preparations according to the invention may contain all additives known per se in cosmetics and medicine.

Preferred dermatological preparations may contain from 20 to 40% by weight of hydrogenated phosphatidylcholine,

0.5 to 40 wt.% Of an active ingredient, wherein the active ingredient in the multilamellar layers of the hydrogenated

Liposome is incorporated, and wherein the active substance has a predominantly lipophilic character, and as additives water, solubilizers and cosmetic auxiliaries and supplements, wherein the sum of the components 100 wt.% Results.

Hydrogenated phosphatidylcholines are present in a lamellar layered structure. In contrast to the known hydrogenated Phosphatidylcholine containing preparations according to the invention, the active ingredients are incorporated to the saturation limit in the layers of hydrogenated phosphatidylcholines. This limit varies depending on the active substance property and is the higher, the more lipophilic the active ingredients are.

Hydrogenated phosphatidylcholines are already known from DE 198 57 489 A1,

DE 198 57 490 A1, DE 198 57 491 A1 and DE 198 57 492 A1. There However, these are added to the end product quasi as auxiliaries or active ingredients and then homogenized the entire finished solution under high pressure. Naturally, all other constituents, as well as the active ingredients, are incorporated into the layers of the hydrogenated phosphatidylcholines 5 and are present in the preparation equilibrium. By this method, on the one hand, the active ingredients only z. T. on the other hand incorporated adjuvants such as preservatives and perfumes with, which is of course not desirable. For this reason, this method is unsuitable for the preparation of the preparations according to the invention.

I O

For example, DE 198 57 491 A1 discloses skin protection preparations for the prevention of skin damage by UV filters while at the same time strengthening the lipid barrier by means of so-called hydrogenated phosphatidylcholines. The proportion of hydrogenated phosphatidylcholines is 0.1 to 10 wt.%. and at 15 UV filters 0.5 to 30 wt.% And of the UV filters, portions are present inside and outside the PC layers.

In the case of the preparations according to the invention, on the other hand, active substances are applied virtually completely as active substances incorporated as hydrogenated phosphatidylcholines (HPC). Since these HPC are stored in the uppermost skin layers, where they remain due to their material properties and release the stored active ingredients by slow diffusion from the HPC matrix, one obtains in this way a kind of depot effect of the stored active substance on the skin. In addition, the stored active substances are largely protected from interaction with other active substances and with atmospheric oxygen, which leads to an improved effect. The preparations according to the invention therefore have fewer active ingredients and do not require penetration-enhancing vehicles. This in turn means that many auxiliaries required in the prior art, which have the task of emulsifying, stabilizing or mobilizing active ingredients, are not necessary in the preparations according to the invention, since the active ingredients are perfectly adequately protected in the abovementioned HPC fins, to the site of action in the skin (the lipid layers of the stratum Corneum), and there fixed as a sort of depot. So it will be only the loaded HPCs suspended in a suitable matrix z. As that of a hydrogel required. This makes it possible to produce low-fiber cosmetics and dermatics whose preparation components serve almost exclusively for the benefit of the target organ, the skin, but not the galenic

Stabilization of the preparation or the preparation constituents, as is often the case with known preparations. Thus, the preparations according to the invention are superior to the known ones in two ways: on the one hand, they have less active ingredient, on the other hand they require less auxiliaries. Both lead to more efficient and compatible preparations.

Hydrogenated phosphatidylcholines in the context of the present invention are generally phosphatidylcholines known per se. Their manufacturing process, for example, proceeds via fractionation of soy lecithin

Phosphatidylcholine and its subsequent hydrogenation to saturation. If these hydrogenated phosphatidylcholines prepared in this way are treated by special technical measures, in particular by high-pressure homogenization, then planar-structured multilamellar systems, hereinafter called dermomembrane systems (DMS), which, in contrast to the non-hydrogenated phosphatidylcholines, no longer have the capability of producing spherical liposomes (LP) to build. The dermal membrane systems (DMS) are structured in a planar lamellar structure. As a result, they still have the ability to fuse with the skin lipid layers, but without fluidizing them and thus locally damaging them. The DMS have no skin penetration potential in contrast to the non-hydrogenated liposomes. Therefore, after fusing, they remain in the natural skin lipid layer until they are shed along with the komeocytes due to natural dermal stimulation.

Hydrogenated phosphatidylcholines for the present invention may be represented by the general formula

CH-O-CO- (CH ₂ ) _n -CH ₃ 5 I

CH ₂ -O-PO ₂ -O-CH ₂ -CH ₂ -N (CHS) ₃

where n is one of the numbers 14 or 16, will be described.

I O

Preferred hydrogenated phosphatidylcholine for the preparation of the starting liposomes is soya lecithin which, after hydrogenation, comprises the hydrogenated phosphatidylcholines of o. G. Formula with n = 14 and / or 16 (palmitoyl and stearoyl) provides.

1 5

Active substances in the context of the present invention may be cosmetic and / or medicinal active substances. In principle, all hydrophilic or lipophilic active ingredients customary in cosmetics and dermatics can be used as active ingredients in the preparations according to the invention, but the loading limit for lipophilic active ingredients is substantially higher.

Cosmetic active substances in the context of the present invention preferably contain lipophilic active substances which are already effective at low concentrations, but also the UV filters required for higher concentrations in 5 light stabilizers.

Medicinal active ingredients in the context of the present invention are known active substances for the treatment of autoimmune diseases, infectious diseases of the skin, inflammatory diseases of other cause or unclear aetiology, erythematosquamous dermatoses, Papulo lichenoid dermatoses, skin tumors, intolerance reactions of the skin, physical and chemical damage to the skin, hereditary Skin diseases, disorders of the appendages and / or pigmentary disorders. The preparations according to the invention can very particularly advantageously be used, for example, for cosmetic or medical sunscreens. These are mostly emulsions or gels that are applied to the skin to protect it from the harmful effects of UV radiation.

The most important criteria for sun protection quality are the UV protection factor (SPF) for UV-B rays and the so-called UV-ABalance for UV-A protection, as defined in the latest Colipa standard (Colipa Activity Report 2005).

Inadequate protection against UV radiation results in addition to the inevitable biological skin aging (intrinsic aging) so-called photoaging, externally visible through additional wrinkling due to the damaging effect of UV light. Skin folds are generally regarded as a measure of skin aging. Apart from photoaging, dehydration is often responsible for insufficient function of the skin lipid membrane.

In order to reduce skin aging caused by light, modern facial care products are equipped with a UV filter combination designed to reduce the UV rays as much as possible. In particular, effective UV-A filters, rather than UV-B filters, are required for daily care, whereas in sunscreens it is reversed. For everyday sun protection without targeted exposure to the sun protection factors of preparations with SPF 4 in Central Europe are sufficient, while a _U. VA balance of 100% and more is needed. Epidermological studies have shown that with consistent use of such efficient amounts of UV filters, wrinkles as a sign of visible aging are greatly reduced. However, the choice of suitable UV-A filters is not great here, because many are limited because of their low solubility or their deactivation-leading interaction with other filters. The preparations according to the invention eliminate these limitations. So z. As the excellent broadband UV filter methylene-bis-benzotriazolyl tetramethylbutylphenol (Tinosorb® M) can be used as water-soluble H PC concentrate, while the prior art requires a surfactant suspension. The UV-A filter Butylmethoxydibenzoylmethane (Avobenzone®) reacts in the light together with the UV-B filter 4-methoxycinnamic acid 2-ethylhexylester with degradation of both substances. On the other hand, if one of them is included in HPC, this degradation will be eliminated and both filters can be used side by side in the same preparation without limitation.

In this way, both the effectiveness of the filter, as well as their adhesiveness and thus their duration of action on the skin is improved because the filter embedded in the application form according to the invention between the multilamellar layers, and thus to a certain extent as a depot and are released gradually.

UV filters in the context of the present invention may be all substances approved in the Colipa positive list UV-A and UV-B filters. It is possible that a mixture of UV-A and UV-B filters is present in the topically acting sunscreen agents according to the invention.

The following UV-A and UV-B filters may be mentioned as preferred: 1- (4'-isopropylphenyl) -3-phenylpropane-1,3-dione, 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl ) -propane-1,3-dione, 2,4-2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 4- (bis (2-hydroxypropyl) amino) benzoic acid ethyl ester, 2-ethylhexyl 4-dimethylaminobenzoate, 3- (4-methylbenzylidene) bornan-2-one, 3-benzyliden-bornan-2-one, 4-methoxycinnamic acid 2-ethylhexyl ester, 4-methoxycinnamic acid propyl ester, A-methoxycinnamic acid isoamyl ester, 2-cyano-3,3-diphenylacrylic acid 2-ethylhexyl ester, 3.3.5-trimethylcylohexyl salicylate, 4-isopropylbenzyl salicylate, octyl salicylate, 2-ethylhexyl salicylate, 2,4,6-trianilino-p- (carbo-2'-ethylhexyl-1'-oxi ) -1,3,5-triazine, methylene-bis-benzotriazolyl tetramethylbutylphenol, ethylhexyl-oxyphenol, methoxyphenyl triazine, 3-imidazol-4-yl-acrylic acid ethyl ester, zinc oxide, titanium dioxide.

Particularly preferred are UV and light filters from the group of dibenzoylmethane, benzophenone, cinnamic acid, triazine, the

Urocaninic acid compounds and from the group of the oxides of zinc and titanium, wherein the filters may be present individually or in a mixture.

Very particular preference in the context of the present invention, the UV filters are methylene-bis-benzotriazolyl tetramethylbutylphenol (Tinosorb® M) and ethylhexyl-oxyphenol methoxyphenyl triazine (Tinosorb® S).

Light stabilizers in the context of the present invention can

5 to 50 wt.% Of hydrogenated phosphatidylcholines and 5 to 50 wt.% Of one or more UV filters in combination, wherein the UV filter is incorporated into the layered structure of the hydrogenated PC, and as additives water, solubilizers and cosmetic auxiliary and

Active ingredients, and wherein the sum of the components 100 wt.% Results.

Preferred light stabilizers in the context of the present invention may comprise 10 to 40% by weight of hydrogenated phosphatidylcholines and 10 to 40% by weight of one or more UV filters in combination, wherein the UV filter is incorporated in the multilamellar layers of the hydrogenated PC, and wherein the UV filter has a predominantly lipophilic character and as additives water, solubilizers and cosmetic auxiliaries and active ingredients, and wherein the sum of the components 100 wt.% Results. The preparations according to the invention can very particularly advantageously be used, for example, for cosmetic or medical preparations against dry skin (moisturizers) and as anti-wrinkle agents,

Humectants and / or anti-wrinkle agents within the scope of the present invention

Invention can

5 to 50% by weight of hydrogenated phosphatidylcholines and 0.5 to 50% by weight of one or more moisturizing active ingredients in combination, wherein the moisturizing and / or anti-wrinkling active ingredient is incorporated in the layered structure of the hydrogenated phosphatidylcholine, and as additives water, solubilizers and cosmetic auxiliaries - and

Active ingredients, and wherein the sum of the components 100 wt.% Results.

The humectants and / or anti-wrinkle agents according to the invention can contain all additives known per se in cosmetics and dermatology.

Preferred humectants and / or anti-wrinkle agents in the context of the present invention can

From 10 to 40% by weight of hydrogenated phosphatidylcholines, from 0.5 to 40% by weight of one or more of the moisturizing and / or anti-wrinkling active ingredients, wherein the moisturizing and / or anti-wrinkling active ingredient is incorporated in the multilamellar layers of the hydrogenated phosphatidylcholine, and wherein the moisturizing and / or anti-wrinkling active substance has a predominantly lipophilic character and contains water, solubilizers and cosmetic auxiliaries and active substances as additives, and the sum of the constituents gives 100% by weight. The preparations according to the invention are surprisingly particularly advantageous against dry skin. Firstly, the hydrogenated phosphatidylcholines have a reinforcing effect on the skin lipid barrier and a favorable effect on skin that is too dry. On the other hand, highly potent skin moisturizers such. As hyaluronic acid and panthenol are incorporated according to the invention in the lamellae of the hydrogenated liposomes and thereby protracted their moisturizing and anti-wrinkle effect and targeted where it is needed, unfold.

Here, too, it can be shown that a preparation produced in this way has a significantly longer action in comparison with a corresponding preparation according to the prior art. Third, the preparations according to the invention are without emulsifiers. Emulsifiers, however, are known to wash natural skin fats out of the skin and are therefore not well suited for the treatment of dry skin.

Preference is given, for example, as humectants vitamin E, vitamin A, lipophilized hyaluronic acid such. As the DSH-CM ^® , panthenol, glycerol and urea and called anti-wrinkle agents ubiquinone or ursolic acid or palmitoyl-pentapeptide (Matrixyl ^® ).

Known additives for the preparations according to the invention may be, for example, oils and fats, salts, moisturizing substances, emulsifiers, preservatives and / or dermatological or cosmetic supplements.

For example, the following additives may be mentioned:

1. fats and oils, such as. B. medium-chain triglycerides (MCT): These are medium-chain triglycerides or triglyceride in the context of the skin protection preparations according to the invention to understand in which straight-chain fatty acids having chain lengths of C ₈ to C ₁₆ are esterified with glycerol. Particularly preferred are triglycerides with fatty acids Cs to C12. Products of this type are traded under different names (eg Myritol 312 and 318 or Miglyo! 810 and 812).

5 2. Salts: These are to be understood in the context of the skin protection preparations according to the invention salts of sodium, potassium, magnesium, calcium, zinc and choline. Preference is given to fluorides, chlorides, sulfates, phosphates, 2-amino-ethyl phosphates, Giycolate, lactates, citrates, succinates, malates, fumarates, Monomethylfumarate, Monoethylfumarate, tartrates or their

10 mixtures. The mixtures may, for. B. also be of natural origin

(Among other sea salt of different provenance, eg from the Dead Sea). Particularly preferred are chlorides, sulfates and fumarates of potassium, sodium and magnesium.

] 3. Humectants: In the context of the skin protection preparations according to the invention are physiologically acceptable polyols, urea or mixtures thereof to understand each other. Typical representatives are glycol, propylene glycol, butylene glycol, hexylene glycol, glycerol, inositol (inositol), sorbitol (sorbitol), mannitol, palatinit, maltodextrin, dextrin, cyclodextrin, 0 glucose, fructose, lactose, mannose, galactose and other saccharides.

Particularly preferred are glycerin, propylene glycol, pentylene glycol and urea.

4. Dermatological and cosmetic supplements of the 5 formulations of the invention are skin wrinkle reducing agents such. Short-chain peptides (argireline, antarcticins and lipophilized peptides (such as palmitolyl-pentapeptide (Matrixyl®)), skin-structurally-improving peptides (collagens such as atelocollagen, desamidocollagen, etc.), skin-protecting lipids and waxes such as Mono-, de-, tri-, and 0 polyglycerides of ricinoleic, 12-hydroxystearic and 11-hydroxypalmitic acid,

Castor oil, hydrogenated castor oil, octyl dodecyl ricinoleic acid, octyl 12-hydroxy stearate, beeswax, Japan wax, carnauba wax, cetyl palmitate, cocoa butter, jojoba oil, shea butter, squalene, Squalane, cholesterol, cholesteryl sulfate, phytosterols, lanolin, lanolin alcohols and their derivatives, ceramides, sphingolipids, sphinganine, sphingosine, sphingosine 1-phosphate, sphingomyelin, C ₁₂ -C ₁₅ alkyl benzoate, linoleic acid methyl and ethyl ester, linoleic acid mono-, di and triglycerides.

Other active ingredients may include vitamins and provitamins (especially A, B complex, C ₁ E, D and their usual derivatives such as vitamin A acid, vitamin A acetate, vitamin A palmitate, vitamin C palmitate, vitamin C phosphate, Vitamin E acetate, palmitate and linoleate, alfacalcidol, calcitriol, colecalciferol, ergocalciferol, folic acid, transcalcifediol, calciprotriol,

Calcifediol, Vitamin D _3, ß-carotene, panthenol, pantothenic acid, biotin), antipruritic Oberflächenanästhetika (eg. As lidocaine, benzocaine, polidocanol, isoprenaline, crotamiton, quinisocaine), antipruritic Hr antihistamines (z. B. meclozine, cetirizine, promethazine , Diphenhydramine, chlophenoxamine, doxylamine, pheniramine, prompheniramine,

Dexchlorpheniramine, bamipine, clemastine, dimetinden, mebhydroline, lorastadine, oxatomide, terfenadine, astemizole), antifungals (eg, econazole, bifonazole, isoconazole, oxiconazole, tioconazole, fenticonazole, clotrimazole, miconazole, ketoconazole, itraconazole, fluconazole, sertaconazole, terbinafine , Naftifine, omoconazole, tolnaftate, amorolfine, amphotericin B, nystatin,

Natamycin, griseofulvin, flucytosine, ciclopirox, tolciclate, undecylenic acid). Anti-inflammatory substances (eg glucocorticoids and their derivatives such as triamcinolone acetonide, bufexamac, chamomile extract, witch hazel extract, tannins, bisabolol, acetylsalicylic acid, allantoin), immunosuppressants (eg methotrexate, cyclosporin), retinoids (eg retinol,

Retinol palmitate, isotretinoin, acitretinoin, tazarotene), anti-infective agents (eg, clindamycin, tetracyclines), cytokines (eg, interleukins, interferons, tumor necrosis factors), antiseptics (eg, chlorhexidine, benzalkonium chloride, 8-hydroxyquinolines, ethacridine, hexetidine , Acriflavinium chloride, benzoxonium chloride, bibrocathol,

Dequalinium salts, ethanol, 2-propanol, 1-propanol, azelaic acid, resorcinol, Triclosan, farnesol, diglycerol monocaprate, colloidal silver, silver chloride, gentamycin, salicylic acid, ozonated olive oil, benzoyl peroxide), antivirals (eg, acyclovir, penciclovir, foscarnet sodium, idoxuridine, trifluridine, tromantadine, vidarabine), astringents (e.g. Tannin, oak bark extract, bismuth gallate),

Extracts with specific effects (eg aloe vera extract, green tea extract, algae extract, echinacea extract, arnica extract, cucumber extract, hops extract, carrot extract, bran extract, witch hazel extract, yeast extract, gingko biloba extract), vegetable oils with specific effects (eg eg rosemary oil, chamomile oil, sage oil, calendula oil, lavender oil, St. John's wort oil,

Lemon balm oil, seabuckthorn oil, tea tree oil, cedar wood oil, cypress oil), oils with a high content of esterified, highly unsaturated (essential) fatty acids (eg evening primrose oil, currant oil, borage oil, rosehip oil, soybean oil, fish oil) and barrier-stabilizing acids (eg linoleic acid, 12-hydroxystearic acid, stearic acid, isostearic acid,

Palmitic acid, 11-hydroxypalmitic acid, protein hydrolyzate condensates ("lipacides", e.g., palmitoyl wheat protein hydrolyzate, dipalmitoyl hydroxyproline, N-palmitoyl glutamic acid), hyaluronic acid) and specific effecting substances (e.g., 1,2-dithiacyclopentane-3-valeric acid, adapalene, ammoidin , Tioxolone, Minoxidil, Fluorouracil).

In addition, the active substances include substances capable of preventing heavy metal cations from penetrating the skin (eg EDTA, 1-hydroxyethane-i, 1-diphosphonic acid, trimethylammonioacetate, cm-glucan, chitosan, polyvinylalcohol, polyvinylpyrrolidone , Bentonites, kaolin, cyclodextrides, pectins and their derivatives, alginic acid and alginates,

Polysaccharides and their derivatives (eg microcrystalline cellulose, cellulose ethers, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carmellose, carboxymethylcellulose, tragacanth, tragacanthine), carrageenans, xanthan, locust bean gum, guar gum and its derivatives, arabic gum, polyacrylates and their copolymers). 5. To the. Supplements include mutatis mutandis, covering substances and pigments such. Magnesium oxide, magnesium carbonate, magnesium aluminum silicate, magnesium stearate, magnesium isostearate, talc, calcium carbonate, zinc oxide, zinc carbonate, zinc stearate, zinc laurate,

5 titanium dioxide, iron oxide, iron hexacyanoferrate, bismuth oxychloride,

Alumina, aluminosilicates, silica, aerosil, boron nitride, mica and minerals, pigments optionally associated with known compatible dyes or tanning agents, e.g. As dihydroxyacetone, may have, in the skin protection preparations according to the invention the

I O meaning, on the one hand to protect against external pollutants, on the other hand to cover localized skin damage or skin abnormalities, in order to protect the skin against corresponding, psychologically induced reactions (scratching, squeezing, etc.).

15 All active substances can be used alone or in a correspondingly meaningful way

Combination be included in the skin protection preparations of the invention. If an adjustment of the pH due to acidic active ingredients is necessary, this can be done by means of indifferent inorganic bases such. For example, sodium hydroxide, potassium hydroxide, or organic bases such. B. 0 triethylamine or triethanolamine done. Particularly preferred active ingredients are linoleic acid and linolenic acid and their esters, palmitic acid, stearic acid and their esters, natural unsaturated oils and fats such as shea butter, jojoba oil, avocado oil, evening primrose oil, currant seed oil, rosehip oil, fish oil, as well as squalane, cholesterol, vitamins of the A-, C- , E-5 and D series and their acetates, palmitates, stearates and linolates or phosphates. In addition, panthenol, biotin, allantoin, lidocaine, salicylic acid, as well as magnesium aluminum silicate, iron oxide, zinc oxide, titanium dioxide, aloe vera extract and mixtures thereof. In addition, proteins such as collagens, short-chain peptides such as Argireline, etc. 0

There has also been found a process for the preparation of topically acting dermatological preparations wherein the active ingredient is incorporated in the multilamellar layers of the hydrogenated phosphatidylcholine characterized in that in a first stage, a mixture of hydrogenated phosphatidylcholine, the active ingredient and optionally water and / or a solvent in the temperature range of about 90 to 11 O ⁰ C prepared and homogenized under high pressure and then in a second stage the other components be added.

In particular, if the active ingredients are not in liquid form, the active compounds are supplied in dissolved form of high-pressure homogenization by the novel process. A suitable solvent must be determined depending on the active ingredient, A suitable solvent should be as little lipophilic as possible, but have a high solubility for the active ingredient.

The homogenization under high pressure in the first stage of the process according to the invention can be carried out in a manner known per se. In general, a homogenization time of about 5 to about 15 minutes is sufficient.

The addition of the further components in the second stage of the process according to the invention can be carried out by customary mixing or stirring.

If such hydrogenated phosphatidylcholines are homogenized under high pressure with active ingredients, the latter are incorporated in the multilamellar layers of the hydrogenated liposome. In the process according to the invention this takes place up to the saturation limit of the active substances in the hydrogenated phosphatidylcholines in order to occupy all free binding sites in the intermediate layers. Subsequently, the hydrogenated phosphatidylcholine active substance concentrates thus prepared are mixed with suitable other components to produce the final product. This is how dermatics and

Cosmetics, which have many advantages over "normal" preparations made with the same active ingredients in the same concentration. In contrast to the skin protection preparations known from DE 198 57 491 A1, the preparation of the sunscreen agents according to the invention takes place in two stages. First, the separate incorporation of the active ingredients in the hydrogenated phosphatidylcholines in the premix to the saturation limit according to the method of high-pressure homogenization described above. This premix is then added to the end products in the required amount. This results in a much higher distribution ratio of active ingredient to hydrogenated phosphatidylcholine than in the conventional procedure which homogenizes the active ingredients in the final product concentration together with all the excipients. This higher distribution quotient has numerous beneficial consequences.

On the one hand, the active ingredient is stably incorporated into the DMS and is therefore no longer available for alternative forms of dispersion. Alternative forms of dispersion are z. As classical micelle formation or classical emulsion formation by means of the emulsifier effect of the hydrogenated phosphatidylcholine and / or the excipients, which are otherwise contained in the final formulation. By means of such alternative emulsions, at least a large part of the active ingredient is emulsified in the conventional process and thereby offered as in classical emulsions. As a result, however, the already indicated advantages of incorporation into the DMS, such as drug stabilization and depot formation, are achieved only to a small extent, namely only to the extent that the active ingredient was present in the high-pressure homogenization of the total formulation mixture in relation to the other formulation constituents. Since drugs are usually used but only in small concentrations based on the final formulation, the desired incorporation into the multilamellar DMS layers is low, and the lower, the lower the final concentration of the active ingredient in the formulation. If you were on the classic, z. B. in DE 198 57 491 A1 described preparation homogenize the known active ingredient Ubiquinone with a target concentration of 0.02 wt.% In the final product, and assuming a concentration of 20 wt.% DMS, it may be assumed that only 20% by weight of 0.02% by weight, ie 0.004% by weight, are present in the desired form embedded in DMS and the main amount is applied to the skin unprotected and free as in any other conventional emulsion. It can be concluded that the inherent advantage of the principle of incorporation of active substance into the DMS lamellae described above is only used to a small extent.

In addition, in the prior art described in DE 198 57 491 A1, other formulation constituents are incorporated into the DMS lamellae and thus the formulation is only available to the extent that they are released again after being applied to the skin , This is z. As undesirable in preservatives and / or perfumes.

In addition, this storage of other formulation components in the DMS slats reduces their capacity for the actual active substance, which of course is likewise undesirable. Since in the prior art process the MCTs are mostly the main lipophilic constituent it may be assumed that predominantly MCT and not as desired the active agent is located between the lamellae.

The present invention is also the use of topically acting dermatological preparations with

10 to 50 wt.% Of hydrogenated phosphatidylcholines and 0.5 to 50 wt.% Of an active ingredient, wherein the active ingredient in the multilamellar layers of the hydrogenated

Phosphatidylcholins is incorporated, and as additives water, solubilizers and cosmetic auxiliary and

Contains supplements, wherein the sum of the ingredients 100 wt.% Results in cosmetic and / or medical preparations.

The preparations according to the invention can preferably be used in light stabilizers. Particularly preferred in the context of the present invention is the use of the preparations according to the invention, the 5 to 50 wt.% Hydrogenated Phosphatidyicholine and 5 to 50 wt.% Of one or more UV filters in combination, wherein the UV filter in the layered structure of the hydrogenated Phosphatidylcholins is incorporated, and as additives water, solubilizers and cosmetic auxiliaries and active ingredients, and wherein the sum of the components 100 wt.% Results as a light stabilizer.

As particularly preferred UV filters, methylene-bis-benzotriazolyl tetramethylbutylphenol and / or ethylhexyl-oxyphenol methoxyphenyl triazine can be used.

The preparations according to the invention can preferably be used in skin moisturizers and / or anti-wrinkle agents.

Particularly preferred in the context of the present invention is the use of the preparations according to the invention in humectants and / or anti-wrinkle agents which

5 to 50% by weight of hydrogenated phosphatidyicholines and

0.5 to 50% by weight of one or more moisturizing active ingredients in combination, the moisturizing and / or anti-wrinkling active ingredient being incorporated in the layered structure of the hydrogenated phosphatidylcholine and containing water, solubilizers and cosmetic auxiliaries and active substances as additives; Sum of ingredients 100 wt.% Results.

The preparations according to the invention can preferably also be used in medical preparations. The preparations according to the invention can preferably be used in gels, creams and lotions.

Examples:

1. Preparation of a concentrate of hydrogenated phosphatidylcholine and

5 broadband UV filter methylene-bis-benzotriazolyl tetramethylbutylphenol

(Tinosorb® M)

There are 20 wt.% Phosphatidylcholine / 40 wt.% Water, 20 wt.% Ethanol with 20 wt.% Methylen-bis-benzotriazolyl tetramethylbutylphenol (pure substance) with stirring under pressure to 80 ⁰ C heated and 30 minutes under pressure at 300 bar homogenized in circulation until a homogeneous

Phase is formed, cooled, and the content of methylene-bis-benzotriazolyl tetramethylbutylphenol determined by UV measurement.

2. Preparation of a cosmetic light stabilizer-money dispersion from the \ 5 concentrate It. 1

The oil phase of 19 wt.% Caprylic / capric triglyceride, 2.5 wt.% Coconut oil, 2 wt.% Jojobaöϊ, 0.1 wt.% Xanthan gum and 0.2 wt.% Carbomer is melted, cooled to 30 ⁰ C. , For this purpose, the water phase of 45.6 wt.% Water, 2.5 wt.% Pentylene glycol, 0 2 wt.% Glycerol and 0.1 wt.% Of a 32 percent. Slowly add the NaOH solution with vigorous stirring and homogenize the mixture to a fluid gel. While stirring, 25% by weight of the concentrate from Example 1 are added and the mixture is homogenized to a white-gloss cream. After the addition of 1% by weight of perfume oil, the mixture is intensively homogenized again and cooled to 25 ^° C. with stirring.

Claims

5 1. Topically acting dermatological preparations containing 10 to 50 wt.% Hydrogenated phosphatidylcholines and 0.5 to 50 wt.% Of an active ingredient, wherein the active substance is incorporated in the multilamellar layers of hydrogenated phosphatidylcholine, and

I O as additives water, solubilizers and cosmetic auxiliaries and supplements, wherein the sum of the components 100 wt.% Results.

2. Topically acting dermatological preparations according to claim 1, 15 containing

From 20 to 40% by weight of hydrogenated phosphatidylcholines containing from 0.5 to 40% by weight of an active compound, the active substance being incorporated in the multilamellar layers of the hydrogenated phosphatidylcholine, and the active substance having a predominantly hydrophobic character, and as additives water, Solubilizers and cosmetic auxiliaries and supplements, the sum of the constituents being 100% by weight. 5

3. Topically acting dermatological preparations according to one of claims 1 to 2, characterized in that the active substance is largely incorporated in the multilamellar layers of the hydrogenated phosphatidylcholine.

4. Topically acting dermatological preparations according to any one of claims 1 to 3, characterized in that the incorporation of the active ingredients in the multilamellar layers of the hydrogenated phosphatidylcholines is carried to saturation with the active ingredient.

5. Topically acting dermatological preparations according to one of claims 1 to 4, characterized in that they contain as additives medium-chain fats and oils, salts, moisture substances and / or dermatological or cosmetic active ingredients.

6. A process for the preparation of topically acting dermatological preparations, wherein the active substance is incorporated in the multilamellar layers of the hydrogenated phosphatidylcholine, characterized in that in a first stage, a mixture of hydrogenated

Phosphatidylcholine, the active ingredient and optionally water and / or a solvent in the temperature range of about 90 to 110 ° C is prepared and homogenized under high pressure and then the other components are added in a second stage.

7. Use of topically acting dermatological preparations with 10 to 50 wt.% Hydrogenated phosphatidylcholines and

0.5 to 50% by weight of an active substance, wherein the active substance is incorporated in the multilamellar layers of the hydrogenated phosphatidylcholine, and as additives water, solubilizers and cosmetic adjuncts and supplements, wherein the sum of the components 100 wt.% Results in cosmetic and / or medical preparations.

8. Use according to claim 7 in sunscreens.

9. Use of a preparation according to claim 8, the 5 to 50 wt.% Hydrogenated phosphatidylcholines and

5 to 50 wt.% Of one or more UV filters in combination, wherein the UV filter is incorporated in the layer structure of the hydrogenated Phosphatidylchölins, and contains as additives water, solubilizers and cosmetic auxiliaries and agents, and wherein the sum of the ingredients 100 wt .%, as a light stabilizer.

10. Use according to one of claims 8 to 9, characterized in that are used as UV filter methylene-bis-benzotriazolyl tetramethylbutylphenol and / or ethylhexyl-oxyphenol methoxyphenyl triazine.

1 1. Use according to claim 7 in moisturizing and / or anti-wrinkle agents.

12. Use according to one of claims 7 or 11, the 5 to 50 wt.% Hydrogenated phosphatidylcholines and

0.5 to 50% by weight of one or more moisturizing active ingredients in combination, the moisturizing and / or anti-wrinkling active ingredient being incorporated in the layered structure of the hydrogenated phosphatidylcholine, and containing water, solubilizers and cosmetic aids and active substances as additives; Sum of ingredients 100% by weight results in humectants and / or anti-wrinkle agents.

13. Use according to claim 7 in medical preparations.

14. Use according to any one of claims 7 to 13 in gels, creams and lotions.