DE19952410B4 - Sunscreen preparations comprising solid lipid nanoparticles - Google Patents

Abstract

feast Lipid nanoparticles comprising at least one UV filter substance, producible by melting a lipid phase, introducing the molten lipid phase in a watery solution at least one surfactant and subsequent high-pressure homogenization.

Description

The The invention relates to sunscreen preparations containing solid lipid nanoparticles comprising at least one UV filter, according to claims 1 with 7th

The damaging Effect of the ultraviolet part of solar radiation on the skin has been known for a long time. To protect the skin from both UVA radiation as well as UVB radiation Numerous chemical and physical filter substances are developed which weaken the effect of the sun's rays.

By Chemical sunscreen filter is the UV radiation striking the skin converted into heat energy. Chemical sunscreen filters can have both lipophilic and hydrophilic properties, and according to these characteristics one distinguishes between oil-soluble ones and water-soluble Filter. For forming a sunscreen preparation, UV filter substances are usually used in cosmetic carriers incorporated and in the form of lotions, creams, ointments and the like formulated. Such formulations are usually based on emulsions. Emulsions are in a broader sense disperse, more or less viscous preparations, consisting of two or more mutually insoluble liquids, of which one is watery. If two immiscible liquids are present and act These are simple emulsion systems, you can basically two Basic types of emulsions differ: oil-in-water emulsions (O / W emulsions) and Water-in-oil emulsions (W / O emulsions). Dependent on from their hydrophilicity filter substances in different Fashion incorporated into the cosmetic vehicle. Water-soluble filters be in the water phase of an emulsion system and oily or oil-soluble filter incorporated into the lipid phase of an emulsion system. Problematic In this incorporation is often poor solubility the filter substances in the water or oil phase of the emulsion system. This is especially true for the very common used solid organic UV filter substances. Because of your poor solubility in the usual way used carrier media can These UV filter substances used only in relatively small amounts become. But now the achievable SPF of a sunscreen preparation depends on the amount of UV filters it contains, it is desirable preferably high concentrations of these solid organic sunscreen filters to realize in sunscreen preparations.

It Various efforts have been made to solubility to increase solid organic sunscreen filter. Such is the case in the PCT application WO 97/25020 described that the Solubility of the Filters Uvinul T150 (available from BASF Aktiengesellschaft) by addition of branched and / or unbranched carboxylic acids with chain lengths from 10 to 24 carbon atoms, which is at least 10% protonated Form, increased can be.

In WO 95/22959 describes sunscreen preparations which insoluble Sunscreen filter in solid micronized form included. The micronization The Filterub punching requires complex milling. By These micronized filters can be obtained only with the addition of emulsifiers in W / O - or O / W emulsion incorporate.

For some time, new carrier materials have been known for drugs based on so-called solid lipid nanoparticles (SLN ^® ), which are described, for example, in German Offenlegungsschrift DE 44 40 337 to be discribed. Solid lipid nanoparticles are particles with a mean particle size in the nanometer range, ie about 80 nm to about 1000 nm. They consist of a solid lipid which is stabilized in aqueous dispersion with a surfactant or polymer. The preparation of the solid lipid nanoparticles is carried out either by high-pressure homogenization of lipids in the molten state (hot homogenization) or in the solid state (cold homogenization). In the hot homogenization, the active ingredient is dissolved in the molten lipid, the molten lipid solution in a hot surfactant solution having a temperature which is about 5 ° C higher than the melting point of the lipid and prepared with a stirrer, a crude emulsion, which then at ca 500 bar high pressure homogenizing. After cooling the resulting nanoemulsion solid lipid nanoparticles form. In cold homogenization, the lipid active ingredient melt is cooled, the solidified lipid is ground into microparticles, which are then suspended in cold surfactant solution. The microparticle suspension obtained is then homogenized in the solid state, the shear and gravitational forces being sufficiently high to comminute the microparticles in the solid state to form fine lipid nanoparticles. As the product, an aqueous dispersion of solid lipid nanoparticles is obtained directly.

task It is the object of the present invention to provide novel sunscreen preparations indicate, with good skin compatibility, an increased sun protection factor have or one opposite previously known sunscreen preparations increased content of UV filter substances to have.

These The object is achieved by means of the independent claim Sunscreen preparation solved.

The dependent claims define advantageous embodiments the invention.

In the investigations on which the present invention is based was surprising found that the for the Range of drugs already described carriers based on solid lipid nanoparticles also as a carrier for UV filter substances and thus used for the preparation of sunscreen preparations can be characterized by a particularly high content of UV filter substances and therefore a high sun protection factor.

According to one embodiment The present invention provides oil-soluble filters which are solid at room temperature according to the known technology for the preparation of solid lipid nanoparticles dissolved in a molten lipid phase and after introduction of the Melt in an aqueous solution of a Tensides high pressure homogenized. Upon cooling, it solidifies in nanodroplets Lipid phase, whereby the filter is in solid solution.

alternative and particularly preferably but also the filter substance itself as the lipid phase used to make solid lipid nanoparticles be used. According to this embodiment In the present invention, the UV filter substance is melted, in an aqueous, at least one surfactant comprising phase dispersed and high pressure homogenized. After cooling, the solid UV filter is in nanoparticle form either crystalline or using suitable crystallization inhibitors, such as. Gelatin PVP or other polymers, in amorphous form in front.

The according to these produced by both alternative methods of the present invention Nanoparticles containing UV filter substances can be converted into customary cosmetic carrier systems, such as O / W creams or emulsions, W / O creams or Lotions or Hydrodispersionsgele be incorporated. The educated Nanodispersion can be particularly advantageous but also directly as a low-viscosity aqueous preparation be applied as a spray on the skin. The inventively produced Sunscreen preparations show in comparison to conventional Sunscreens at the same concentrations of UV filter substances an increased by at least a factor of 2 to 4 light protection factor. Further Advantages of the sunscreen preparations according to the invention, presumably based on the fact that the filter substances in a fat matrix are an increased water resistance, a lower skin penetration, resulting in improved tolerability the preparations according to the invention results, as well as an increased photostability the UV filter substances.

The preparation of the sunscreen preparations according to the invention is in itself unproblematic and takes place according to the already known regulations for the preparation of nanosuspensions of solid lipid nanoparticles; Reference is made by way of example to the method disclosed in DE OS 44 40 337. As stated above, the lipid phase used for producing the UV filter-containing nanoparticles according to the invention can either consist of the filter substance itself or else be formed by customary lipids, such as, for example, cetyl palmitate, beeswax or tristearin. The surfactants used to form the solid lipid nanoparticles according to the invention are preferably substances which show good skin tolerance. Particularly preferred is the use of cholesterol, lecithin or methylglucosides such as those from the Tego- ^Care® series. In addition to the UV filters contained in the lipinanoparticles, the preparations according to the invention may comprise further UV filter substances, in particular also physical filter substances.

The nanoparticle dispersions according to the invention preferably comprise from 0.1 to 50% by weight of nanoparticles. The salary of nanoparticles according to the invention on UV filter substance is between 0.1 and 100 wt .-%. The salary the nanodispersion in the sunscreen preparations according to the invention is between 0.1 and 100 wt .-%.

The The following examples illustrate the invention.

example 1

A UV filter substance-containing nanoparticle suspension of the following composition is produced: ingredient Content [% by weight] Uvinul T150 30 cholesterol 2 Tego Care ^® 4 glycerol 3 ethanol 5 water ad. 100

Uvinul T150 UV filter (2,4,6-trianilino-p- (carbo-2'-ethyl-hexyl-1'-oxy) 1,3,5-triazine) was melted and placed in an aqueous solution of cholesterol and Tego Care ^® introduced, which had a temperature of about 5 ° C above the melting temperature of the UV filter. The resulting emulsion is dispersed in a high pressure homogenizer to nanoparticles and the resulting nanoemulsion is then cooled. Then glycerol and ethanol are added. The nanoparticle dispersion thus obtained can be applied directly to the skin as a spray.

Example 2

It nanoparticle dispersions were prepared according to Example 1, at which instead of UV filter Uvinul T150 the UV filter UVA Sorb HEB or Eusolex 6300 and / or Parsol 1789 were used.

Example 3

A nanoparticle dispersion of the following composition is prepared: ingredient Content [% by weight] Uvinul T150 5 tristearin 30 Tego Care ^® 5 lecithin 0.5 glycerol 3 water ad. 100

First, a melt of tristearin and Uvinul T150 was formed, which was introduced into a solution of Tego Care ^® and lecithin, which had a temperature of about 5 ° C above the temperature of the melt. As previously described in Example 1, a nanodispersion is formed by high-pressure homogenization. After cooling the resulting dispersion, glycerol is added. The dispersion thus obtained can be applied directly to the skin in the form of a spray.

Example 4

Corresponding Example 3 nanoparticle dispersions were prepared in which instead of the Uvinul T150 the UV filters UVA Sorb HEB or Eusolex 6300 or Parsol 1789 were used.

Example 5

An oil-in-water emulsion of the following composition is prepared: ingredients Content [% by weight] UV nanoparticle dispersion according to Example 1-4 25 Tego ^Care® 450 2 Softisan 100 0.5 cetyl alcohol 1.5 Myritol 331 5 α-tocopherol acetate 1 Carbopol 981 0.2 glycerol 3 caustic soda 0.05 ethanol 7 water ad. 100

Example 6

A water-in-oil lotion of the following composition is produced: ingredients Content [% by weight] UV nanoparticle dispersion according to Example 1-4 25 Dehymuls PGPH 3 Monomuls 90-018 1 Myritol 318 6 isopropyl 10 Vitamin E acetate, liquid 0.5 beeswax 1 magnesium stearate 0.5 Neo Heliopan AV 10 Sodium EDTA disodium 0.1 glycerin 3.0 dexpanthenol 1.0 magnesium sulfate 0.5 ethanol 8th water ad. 100

Example 7

A hydrodispersion gel of the following composition is prepared: ingredients Content [% by weight] UV nanoparticle dispersion according to Example 1-4 25 Pemulen TR1 0.5 Sodium EDTA disodium 0.1 glycerol 3.0 dexpanthenol 1.0 Neo Heliopan AV 5 Neo Heliopan 1000 5 DL-α-tocopherol 0.5 sodium hydroxide 0.19 alcohol 9 water ad. 100

Claims (7)

Solid lipid nanoparticle comprising at least a UV filter substance, producible by melting a lipid phase, Introducing the molten lipid phase into an aqueous solution at least a surfactant and subsequent High pressure homogenization. Photoprotective composition comprising an aqueous dispersion of solid lipid nanoparticles containing at least one UV filter substance, preparable by melting a lipid phase, introducing the molten zens lipid phase in an aqueous solution of at least one surfactant and subsequent high-pressure homogenization. Sunscreen preparation according to claim 2, characterized that she 0.1 to 50% by weight of solid lipid nanoparticles. Light protection preparation according to claim 2 or 3, characterized in that the selected at least one UV filter substance selected from the group consisting of octyl triazone (Uvinul ^® T150), dioctylbutylamidotriazone (UVA Sorb HEB ^®), 3- (4-methylbenzylidene) (Eusolex ^® 6300 ) and butylmethoxydibenzoylmethane (Parsol ^® 1789). Sunscreen preparation according to one of claims 2 to 4, characterized in that except the at least one contained in the solid lipid nanoparticles UV filter substance at least one more, not in the solid lipid nanoparticles contained UV filter substance. Sunscreen preparation according to claim 5, characterized in that that the not included in the lipid nanoparticles UV filter substance physical sunscreen is. Sunscreen preparation according to claim 6, characterized that the Exclusively lipid phase at least one UV filter substance is formed.