WO2000015329A1

WO2000015329A1 - Method for producing nanoparticles

Info

Publication number: WO2000015329A1
Application number: PCT/EP1999/006527
Authority: WO
Inventors: Christian Kropf; Hans Dolhaine; Thomas Förster; Karlheinz Schaber; Michael Türk; Stephan Cihlar; Peter Christophliemk
Original assignee: Henkel Kommanditgesellschaft Auf Aktien
Priority date: 1998-09-15
Filing date: 1999-09-04
Publication date: 2000-03-23
Also published as: AU5745599A

Abstract

The invention relates to a method for producing nanoparticles with diameters of between 10 and 300 nm, comprising the following steps: (a) dissolving organic active agents in a solvent in supercritical or near-critical conditions; (b) expanding the fluid mixture into a gas or a liquid using a nozzle; and (c) evaporating the solvent at the same time. The method is characterised in that emulsifiers and/or protective colloids are also used.

Description

Process for the production of nanoparticles

Field of the Invention

The invention is in the field of nanoparticles and relates to particles with a diameter in the range from 10 to 300 nm, which are obtained by dissolving organic active substances under supercritical or near-critical conditions and then spraying in the presence of emulsifiers and / or protective colloids.

State of the art

The production of nanoparticles is currently one of the most expanding research topics in the field of cosmetic active ingredients. Representing the large number of publications on the subject of finely divided organic active substances, the so-called “nanoorganics”, reference is made to the Australian patent AU-B 10708/88 (BASF), from which a process for the production of nanoparticles is known in which organic substances are known , in this case carotenoids, together with suitable emulsifiers, dissolve in water-miscible solvents and edible oils and stir into an aqueous protective colloid solution The nanoparticles are then isolated by distillation and spray drying, but this process is technically very complex.

From the article by S.Chihlar, M.Türk and K.Schaber in Proceedings World Congress on Particle Technology 3, Brighton, 1998, the process for the production of nanoparticles by rapid relaxation of supercritical solutions (Rapid Expansion of Supercritical Solutions RESS) is known. In this process, for example, cholesterol is dissolved in supercritical carbon dioxide and the solution is released into a vacuum chamber. However, the nanoparticles obtained in this way bake together again in the shortest possible time and are then no longer usable for cosmetic applications.

Accordingly, the object of the method according to the invention was to provide an improved method for producing organic nanoparticles (“nanoorganics”) which avoids the disadvantages of the prior art and thereby in particular with as little effort as possible, delivers nanoparticles of the desired grain size range that do not agglomerate during storage. In addition, the process should ensure that there is no process-related decomposition of the starting materials.

Description of the invention

The invention relates to a method for producing nanoparticles with diameters in the range from 10 to 300, preferably 50 to 150 nm, in which

(a) dissolves organic active substances in a solvent under supercritical or near-critical conditions,

(b) the fluid mixture is expanded into a gas or liquid via a nozzle, and

(c) the solvent evaporates at the same time,

which is characterized in that emulsifiers and / or protective colloids are also used.

Surprisingly, it was found that the use of emulsifiers or protective colloids, either in the preparation or the spraying of the supercritical or near critical solutions, leads to nanoparticles which do not cake. The process even allows the production of enzymes in nanoform without causing any signs of decomposition.

Organic active ingredients

The following compounds are suitable as organic active substances which can be converted into nanoparticles in the sense of the process according to the invention:

Sterols (or synonym stenols) are animal or vegetable steroids to be understood which only carry a hydroxyl group at C-3, but no other functional groups. As a rule, the sterols have 27 to 30 carbon atoms and a double bond in 5/6, optionally 7/8, 8/9 or other positions. In addition to these unsaturated species, sterols also include the saturated compounds obtainable by curing, which are referred to as stanoia and are included in the present invention. An example of a suitable animal sterol is cholesterol. Typical examples of suitable phytosterols, which are preferred for technical reasons, are, for example, ergosterols, Campesterols, stigmasterols, brassica sterols and preferably sitosterols or sitostanols and in particular ß-sitosterols or ß-sitostanoia. In addition to the phytosterols mentioned, their esters are preferably used. The acid component of the ester can be traced back to carboxylic acids of the formula (I)

R ¹ CO-OH (I)

in which R ¹ CO is an aliphatic, linear or branched acyl radical having 2 to 22 carbon atoms and 0 and / or 1, 2 or 3 double bonds. Typical examples are acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, caprylic acid, 2-ethyl hexanoic acid, capric acid, lauric acid, isotridecanoic acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, elaidic acid, petroselinic acid, linoleic acid, conjugated linoleic acid (CLA) , Linolenic acid, elaeostearic acid, arachic acid, gadoleic acid, behenic acid and erucic acid and their technical mixtures, which are obtained, for example, in the pressure splitting of natural fats and oils, in the reduction of aldehydes from Roelen's oxosynthesis or as a monomer fraction in the dimerization of unsaturated fatty acids. Technical fatty acids with 12 to 18 carbon atoms, such as coconut, palm, palm kernel or tallow fatty acids, are preferred. The use of esters of β-sitosterol or β-sitostanol with fatty acids having 12 to 18 carbon atoms is particularly preferred. These esters can be prepared either by direct esterification of the phytostenols with the fatty acids or by transesterification with fatty acid lower alkyl esters or triglycerides in the presence of suitable catalysts, such as sodium ethylate or especially also enzymes [cf. EP-A2 0195311 (Yoshikawa)].

Typical examples of antioxidants are amino acids (e.g. glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (e.g. urocanic acid) and their derivatives, peptides such as D, L-carnosine, D-camosine, L-camosine and their derivatives (e.g. anserine ), Carotenoids, carotenes (e.g. α-carotene, ß-carotene, lycopene) and their derivatives, chlorogenic acid and their derivatives, lipoic acid and their derivatives (e.g. dihydroiiponic acid), aurothioglucose, propylthiouracil and other thiols (e.g. thioredoxin, glutathione, cysteine, cystine , Cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ-linoleyl,

Cholesteryl and glyceryl esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulfoximine compounds (for example Buthioninsulfoximine, homocysteine sulfoximine, Butioninsulfone, penta-, hexa-, Heptathioninsuifoximin) in very low tolerable doses (e.g. pmol to μmol / kg), further (metal) chelators (e.g. α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (e.g. citric acid, Lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and their derivatives, unsaturated fatty acids and their derivatives (e.g. γ-linolenic acid, linoleic acid, oleic acid), folic acid and its derivatives, ubiquinone and ubiquinol and their derivatives, Vitamin C and derivatives (e.g. ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (e.g. vitamin E acetate), vitamin A and derivatives (vitamin A palmitate) as well as coniferyl benzoate of benzoin, rutinic acid and its derivatives, α- Glycosylrutin, Ferulasäure, Furfurylidenglucitol, Camosin, Butylhydroxytoluol, Butylhydroxyanisol, Nordihydroguajakarzarzäure, Nordihydroguajaretsäure, Rosmarinsäure, Trihydroxybutyrophenon, uric acid and its derivatives, Mannose and its derivatives, eg Selenium-methionine), stilbenes and their derivatives (eg stilbene oxide, trans-stilbene oxide) and those which are suitable according to the invention eten derivatives (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these active ingredients.

Flavones, such as Flavon (primrose), chrysin (poplar), galangin (glagantroot), apigenin (snapdragon, chamomile, dahlia), luteolin (foxglove, dahlia), camphor oil (buckthorn, delphinium, sloe), quercutin (oak, gold lacquer, pansy), quercetin (Oak, gold lacquer, pansies), morin (mulberry), robinetin (acacia), gossynetin (cotton, hibiscus), myricetin (currant, hamameiis), fisetin (fisetholz), rutin (citrus fruits, pansies, linden flowers, tea, St. John's wort, acacia ), Hesperidin (orange peel), naringin (grapefruit), daidzein (soy), genistein (soy, red clover), prumetin (plum tree), biochanin (chickpea, clover), santal (sandalwood, redwood), prateness (clover), bioflavonoids Gingko, yew and cypress.

Synthetic or natural waxes can also be used, e.g. Paraffin waxes, hydrogenated castor oil, cetyl plasticity, ethylene oxide waxes, pearlescent waxes, camauba wax, beeswax, sunflower wax and apple wax.

Also suitable as starting materials are fatty acids and fatty alcohols having 12 to 22 carbon atoms which are solid at room temperature, such as, for example, lauric acid, isotridecanoic acid, myristic acid, palmitic acid, stearic acid and behenic acid and their technical mixtures, or cetyl alcohol, palmoleyl alcohol, stearyl alcohol and behenyl alcohol and their technical mixtures . Mixtures of the fatty alcohols mentioned with alkylpolyglucosides are also suitable, mixtures of cetearyl alcohol with cetearylglucosides in a mixing ratio of 10:90 to 90:10 being particularly preferred. Metal soaps, such as the calcium, magnesium, aluminum and / or zinc salts of carboxylic acids having 10 to 18 carbon atoms, in particular undecylenic acid, stearic acid, hydroxystearic acid or ricmolic acid, are also suitable as starting materials for the process according to the invention

Suitable dyes are, for example, direct dyes from the group of nitrophylenediamines, nitroaminophenols, anthrachmones or indophenols, such as, for example, those with the international names or trade names HC Yellow 2, HC Yellow 4, Basic Yellow 57, Disperse Orange 3, HC Red 3, HC Red BN, Basic Red 76, HC Blue 2, Disperse Blue 3, Basic Blue 99, HC Violet 1, Disperse Violet 1, Disperse Violet 4, Disperse Black 9, Basic Brown 16, Basic Brown 17, Picramic Acid and Rodol 9 R known compounds and 4-amino-2-nitro-phenylamine-2'-carboxylic acid 6-nitro-1, 2,3,4-tetrahydro-chlorooxaline, (N-2,3-dihydroxypropyl-2-nitro-4-trifluoromethyl) aminobenzene and 4-N-ethyl-1, 4-bιs (2'-hydroxyethylamιno) -2-nιtrobenzol- hydrochloπd Furthermore, naturally occurring dyes such as henna red henna neutral henna black, chamomile blood, sandalwood, black tea, rotten bark, Sage blue wood, madder root, catechu, sedre and alka nnawurzei as well as indigo, cochineal, shikonin, Alizaπn, juglon and hematoxilin can be used as an alternative. Oxidation dyes consisting of developer and coupler components can be used. The developer components are, for example, aromatic aromatic nurse with another free or substituted one that is in the para or ortho position Hydroxy or amino group, diaminopyπdindeπvate heterocyclic hydrazones, 4-aminopyrazolone deπvate and 2,4,5,6-tetraaminopyπmidine and its derivatives used. Special representatives include p-toluenediamine p-aminophenol N, N-Bιs- (2-hydroxy-ethyl ) -p-Phenylenedιamιn, 2- (2,5-Dιamιno- phenoxy) ethanol 1-phenyl-3-carboxyamιdo-4-amino-pyrazolone-5 and 4-amino-3-methylphenol, 2- (2-hydroxyethyl ) -1 4-aminobenzene and 2.4 5 6-tetraaminopyπmιdιn Usually m-phenylenediamine pvate, naphthols, resorcinol and resorcinole pvate, pyrazolone, m-aminophenole as well as pyπdine deπvate are used as coupler components. As Ku Plpler substances are particularly suitable 1-naphthol pyrogallol, 1, 5-, 2,7- and 1, 7-dihydroxynaphthalene, 5-amino-2-methylphenol, m-aminophenoi resorcinol, resorcinol monomethyl ether, m-phenylenediamine, 1-phenyl-3- methyl-pyrazolon-5 2,4-dichloro-3-aminophenol, 1, 3-bis (2,4-diminophenoxy) propane, 2-chlororesorcinol, 2-chloro-6-methyl-3-aminophenol, 2-methyl resorcinol , 2,5-Dimethylresorcιn, 2,6-Dihydroxypyπdm and 2,6-Dιamιnopyπdιn Furthermore, natural color pigments from plants, such as chlorophylls carotenes and anthocyanins, can also be used

UV light barrier factors suitable for the production of nanopigments are, for example 3-benzylidene camphor or 3-benzylidene norcampher and its derivatives, for example 3- (4-methylbenzylidene) camphor as described in EP-B1 0693471;

4-aminobenzoic acid derivatives, preferably 2-ethylhexyl 4- (dimethylamino) benzoate, 2-octyl 4- (dimethylamino) benzoate and amyl 4- (dimethylamino) benzoate;

Esters of cinnamic acid, preferably 4-methoxycinnamic acid 2-ethylhexyl ester, 4-methoxycinnamic acid propyl ester, 4-methoxycinnamic acid isoamyl ester 2-cyano-3,3-phenylcinnamic acid 2-ethylhexyl ester (octocrylene);

• esters of salicylic acid, preferably 2-ethylhexyl salicylate, 4-isopropylbenzyl salicylic acid, homomenthyl salicylic acid;

• derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-meth-oxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone;

• Esters of benzalmalonic acid, preferably di-2-ethylhexyl 4-methoxybenzmalonate;

Triazine derivatives, e.g. 2,4,6-trianilino- (p-carbo-2'-ethyl-1'-hexyloxy) -1, 3,5-triazine and octyl triazone, as described in EP-A1 0818450;

Propane-1,3-dione, e.g. 1- (4-tert-butylphenyl) -3- (4'methoxyphenyl) propane-1,3-dione;

• Ketotricyclo (5.2.1.0) decaπ derivatives, as described in EP-B1 0694521.

• 2-phenylbenzzimidazole-5-sulfonic acid and its alkali, alkaline earth, ammonium, alkylammonium, alkanolammonium and glucammonium salts;

Sulfonic acid derivatives of benzophenones, preferably 2-hydroxy-4-methoxybenzophenone-5-sulphonic acid and their salts;

Sulfonic acid derivatives of 3-benzyiide camphor, e.g. 4- (2-oxo-3-bornylidene-methyl) beπzolsulfonic acid and 2-methyl-5- (2-oxo-3-bornylidene) sulfonic acid and their salts.

Benzoylmethane derivatives, such as, for example, 1- (4'-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione, 4-tert-butyl-4'-methoxydibenzoylmethane (Parsol 1789), or 1-phenyl-3- (4'-isopropylphenyl) propane-1,3-dione.

Further suitable UV light protection filters can be found in the overview by P.Finkel in SÖFW-Journal 122, 543 (1996).

Suitable starting materials are also fragrances. Natural fragrances are extracts of flowers (lily, lavender, roses, jasmine, neroli, ylang-ylang), stems and leaves (geranium, patchouli, petitgrain), fruits (anise, coriander, caraway, juniper), fruit peel (bergamot, lemon, Oranges), Roots (Macis, Angelica, Celery, Cardamom, Costus, Iris, Calmus), Woods (Pine, San del, Guaiac, Cedar, Rosewood), Herbs and Grasses (Tarragon, Lemongrass, Sage, Thyme ), Needles and twigs (spruce, fir, pine, mountain pine), resins and balsams (galbanum, elemi, benzoin, myrrh, olibanum, opoponax). Animal raw materials, such as civet and castoreum, are also suitable. Typical Synthetic fragrance compounds are products of the ester, ether, aldehyde, ketone, alcohol and hydrocarbon type. Fragrance compounds of the ester type are, for example, benzyl acetate, phenoxyethyl isobutyrate, p-tert-butylcyclohexyl acetate, linalyl acetate, dimethylbenzylcarbinyl acetate, phenylethyl acetate, linalyl benzoate, benzyl formate, ethyl methylphenyl glycinate, allyl cyclohexyl benzylatepylatepylatepylatepylatepylatepylatepylate, stylatepylatepylate. The ethers include, for example, benzylethyl ether, the aldehydes include, for example, the linear alkanals having 8 to 18 carbon atoms, citral, citronellal, citronellyloxyacetaldehyde, cyclamenaldehyde, hydroxycitronellal, lilial and bourgeonal, and the ketones include, for example, the jonones, α-isomethylionone and methyl cedryl ketone , the alcohols anethole, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol and teφineol, the hydrocarbons mainly include the terpenes and balsams. Ambroxan, heliotropin, vanillin, ethylvanillin, coumarin, camphor, menthol, indole and maltol as well as the extracts of rice, rice husks, myrrh, olibanum, mistletoe and salvia sclarea are also suitable.

Enzymes can also be used in the process, e.g. Choline oxidase (from bacteria), peroxidase (from soybeans), laccases and tyrosinases (from fungi); Suitable enzyme inhibitors are e.g. Phenylboronic acid and its derivatives, Gly-Pro-Phe-Pro-Leu pentapeptides and peptides containing this sequence, bacitracin, aminoethylbenzenesulfonyl fluoride, all of which are effective as serine protease inhibitors for regulating skin flaking. Koji acid, arbutin, epicatechin gallate, bacelaine, dihydromyrecitin, ascorbic acid and 1000-1500 D proteins from silk protein hydroylsates can be used as tyrosinase inhibitors (skin whiteners). For example, cholesterol and phytosterol sulfate can be used as elastase inhibitors for skin rejuvenation

Furthermore, all other cosmetic ingredients that are solid at room temperature, such as e.g.

Chitin and chitin derivatives, e.g. Chitosan,

Phospholipids (lecithins),

Salicylic acid amide

Caffeine

Allantoin

Boswellic acid,

Ferulic acid,

Glycyrrhizin,

Oryzanol

Inulin can be converted into nanoparticles by the process according to the invention.

Solve under supercritical or near critical conditions

If liquids or gases are heated under pressure, they finally get into the supercritical or fluid state above their respective critical conditions, in which they are present as liquids which are distinguished by a particularly low density, low viscosity and a very high diffusion coefficient. Typical examples of liquids or gases which are considered as supercritical solvents in the context of the invention are carbon dioxide, ethylene, propane, ammonia, methanol, nitrous oxide, nitrous oxide, sulfur hexafluoride, difluoromethane, trifluoromethane, water, toluene and a number of nitrogen heterocycles; Mixtures of the gases mentioned can also be used. Information on the behavior of supercritical liquids and gases can be found, for example, in Angew.Chem. 92: 585-598 (1980) and ibid. 93: 907-911 (1981). The conditions under which a substance changes to the supercritical state are of course substance-specific. For the preferred solvent carbon dioxide, however, a temperature range of 0 to 200 and preferably 40 to 100 ° C. and a pressure range of 10 to 300, preferably 20 to 200 bar are recommended; in principle, these areas can also be transferred to other substances. Usually the sterols and sterol esters are placed in a suitable pressure vessel, the reactor is closed and the solvent, preferably carbon dioxide, is injected until the desired pressure is reached. The temperature is then increased until the mixture changes to the supercritical state. In a preferred embodiment of the invention, the organic active ingredients are dissolved together with emulsifiers and / or protective colloids, which may be present in substance as aqueous or alcoholic solutions or in mixtures with cosmetic oils.

Spray

After the organic active ingredients, if appropriate in the presence of the emulsifiers and / or protective colloids, have been dissolved under supercritical or near-critical conditions, the solutions are sprayed through a nozzle, which results in the production of particles with a particularly fine particle size, namely so-called nanoparticles . The process, which is also referred to as "jet spraying" or "rapid expansion of supercritical solutions (RESS)", can be carried out in a manner known per se, ie the reactor is discharged with a suitable fine nozzle and the spraying is carried out continuously by you open the exit and the The reactor is carefully relaxed. The same conditions apply for the spray temperature as for the dissolving process. If the active ingredients have not been dissolved in the presence of suitable protective colloids or emulsifiers, the teaching of the invention is to relax the substances not in air or water, but in aqueous and / or alcoholic solutions of emulsifiers and / or protective colloids in order to prevent undesirable caking of the To prevent particles. It is also possible to relax the fluid mixtures directly into the protective colloid, for example in polyethylene glycol, so that the use of water or alcohol is unnecessary. Finally, it is also possible to dissolve the emulsifiers and / or protective colloids in cosmetic oils and to relax the active ingredients in these mixtures.

Emulsifiers

Examples of suitable emulsifiers are nonionic surfactants from at least one of the following groups:

(1) Addition products of 2 to 30 moles of ethylene oxide and / or 0 to 5 moles of propylene oxide with linear fatty alcohols with 8 to 22 C atoms, with fatty acids with 12 to 22 C atoms and with alkylphenols with 8 to 15 C atoms in the Alkyl group;

(2) Ci2 / i8 fatty acid monoesters and diesters of adducts of 1 to 30 moles of ethylene oxide with glycerol;

(3) glycerol monoesters and diesters and sorbitan monoesters and diesters of saturated and unsaturated fatty acids having 6 to 22 carbon atoms and their ethylene oxide addition products;

(4) alkyl mono- and oligoglycosides with 8 to 22 carbon atoms in the alkyl radical and their ethoxylated analogs;

(5) adducts of 15 to 60 moles of ethylene oxide with castor oil and / or hardened castor oil;

(6) polyol and especially polyglycerol esters such as e.g. Polyglycerol polyricinoleate, polyglycerol poly-12-hydroxystearate or polyglycerol dimerate. Mixtures of compounds from several of these classes of substances are also suitable;

(7) adducts of 2 to 15 moles of ethylene oxide with castor oil and / or hardened castor oil;

(8) partial esters based on linear, branched, unsaturated or saturated C6 / 22 fatty acids, ricinoleic acid as well as 12-hydroxystearic acid and glycerin, polyglycerin, pentaerythritol, dipentaerythritol, sugar alcohols (e.g. sorbitol), alkyl glucoside (e.g. methyl glucoside), butyl glucoside Polyglucosides (eg cellulose); (9) mono-, di- and trialkyl phosphates and mono-, di- and / or tri-PEG-alkyl phosphates and their salts;

(10) wool wax alcohols;

(11) polysiloxane-polyalkyl-polyether copolymers or corresponding derivatives;

(12) mixed esters of pentaerythritol, fatty acids, citric acid and fatty alcohol according to DE-PS 1165574 and / or mixed esters of fatty acids with 6 to 22 carbon atoms, methyl glucose and polyols, preferably glycerol or polyglycerol and

(13) Polyalkylene glycols.

The adducts of ethylene oxide and / or of propylene oxide with fatty alcohols, fatty acids, alkylphenols, glycerol mono- and diesters as well as sorbitan mono- and diesters of fatty acids or with castor oil are known, commercially available products. These are homogeneous mixtures, the medium of which Degree of alkoxylation corresponds to the ratio of the amounts of substance of ethylene oxide and / or propylene oxide and substrate with which the addition reaction is carried out. Ci2 / i8 fatty acid monoesters and diesters of adducts of ethylene oxide with glycerol are known from DE-PS 2024051 as refatting agents for cosmetic preparations.

Cβ-alkyl mono- and oligoglycosides, their preparation and their use are known from the prior art. They are produced in particular by reacting glucose or oligosaccharides with primary alcohols with 8 to 18 carbon atoms. Regarding the glycoside residue, both monoglycosides in which a cyclic sugar residue is glycosidically bonded to the fatty alcohol and oligomeric glycosides with a degree of oligomerization of up to about 8 are suitable. The degree of oligomerization is a statistical mean value which is based on a homolog distribution customary for such technical products.

Zwitterionic surfactants can also be used as emulsifiers. Zwitterionic surfactants are surface-active compounds that contain at least one quaternary ammonium group and at least one carboxylate and one sulfonate group in the molecule. Particularly suitable zwitterionic surfactants are the so-called betaines such as the N-alkyl-N, N-dimethyl-ammonium glycinate, for example the coconut alkydimethylammonium glycinate, N-acyl-aminopropyl-N, N-dimethylammonium glycinate, for example the coconut acyl aminopropyldimethylammonium 2-cyanate -Alkyl-3-carboxylmethyl-3-hydroxyethylimidazolines each having 8 to 18 carbon atoms in the alkyl or acyl group and the cocoacylaminoethylhydroxyethylcarboxymethylglycinate. The fatty acid amide derivative known under the CTFA name of Cocamidopropyl Betaine is particularly preferred. Suitable emulsifiers are ampholytic surfactants. Ampholytic surfactants are understood to mean those surface-active compounds which, apart from a Cβπs alkyl or acyl group, at least in the molecule contain a free amino group and at least one -COOH or -S0 ₃ H group and are capable of forming internal salts. Examples of suitable ampholytic surfactants are N-alkylglycines, N-alkylpropionic acids, N-alkylaminobutyric acids, N-alkyliminodipropionic acids, N-hydroxyethyl-N-alkylamidopropylglycines, N-alkyltaurines, N-alkylsarcosines, 2-alkylaminopropionic acids and alkylaminoacetic acids each with about 8 bisacid acids 18 carbon atoms in the alkyl group. Particularly preferred ampholytic surfactants are N-cocoalkylaminopropionate, cocoacylaminoethylaminopropionate and Ci2 / i8-acylsarcosine. In addition to the ampholytic emulsifiers, quaternary emulsifiers are also suitable, those of the esterquat type, preferably methylquaternized difatty acid triethanolamine ester salts, being particularly preferred.

Protective colloids

In many cases, the terms protective colloid and emulsifier can be used interchangeably. In a strictly scientific sense, protective colloids are, however, lyophilic colloids such as, for example, gelatin, casein, gum arabic, lysalbic acid, starch and polymers, such as polyvinyl alcohols, polyvinyl pyrrolidones, polyalkylene glycols and polyacrylates. Usually, both the emulsifiers and the “real” protective colloids, either in substance or in the form of aqueous, occasionally also aqueous-alcoholic solutions in amounts of 0.1 to 20, preferably 5 to 15,% by weight, based on the organic active substances. used.

Cosmetic oils

Cosmetic oils include, for example, Guerbet alcohols based on fatty alcohols with 6 to 18, preferably 8 to 10 carbon atoms, esters of linear Cε-C∑∑ fatty acids with linear C6-C22 fatty alcohols, esters of branched C6-Ci3 carboxylic acids with linear C6 -C22- fatty alcohols, esters of linear C6-C ₂ fatty acids with branched alcohols, in particular 2-ethylhexanol, esters of hydroxycarboxylic acids with linear or branched Cβ-C∑∑ fatty alcohols, in particular dioctyl malates, esters of linear and / or branched Fatty acids with polyhydric alcohols (such as propylene glycol, dimer diol or trimer triol) and / or Guerbet alcohols, triglycerides based on Cβ-Cio fatty acids, liquid mono- / di- / triglyceride mixtures based on C6-Ci8-fatty acids, esters of C6- C22 fatty alcohols and / or Guerbet alcohols with aromatic carboxylic acids, in particular benzoic acid, esters of C2-C12 dicarboxylic acids with linear or branched alcohols with 1 to 22 cabbages Substance atoms or polyols with 2 to 10 carbon atoms and 2 to 6 hydroxyl groups, vegetable oils, branched primary alcohols, substituted cyclohexanes, linear and branched C6-C22 fatty alcohol carbonates, Guerbet carbonates, esters of benzoic acid with linear and / or branched C6-C22- Alcohols (e.g. Finsolv® TN), linear or branched, symmetrical or asymmetrical dialkyl ethers with 6 to 22 carbon atoms per alkyl group, ring opening products of epoxidized fatty acid esters with polyols, silicone oils and / or aliphatic or naphthenic hydrocarbons.

Examples

Examples 1 to 14. The gaseous solvent was removed from a reservoir at a constant pressure of 60 bar and purified over a column with an activated carbon and a molecular sieve packing. After the liquefaction, the solvent was compressed to the desired supercritical pressure p using a diaphragm pump at a constant flow rate of 3.5 l / h. The solvent was then brought to the required temperature T1 in a preheater and passed into an extraction column (steel, 400 ml) which was loaded with the organic active ingredient. The resulting supercritical, i.e. The fluid mixture was sprayed through a laser-drawn nozzle (length 830 μm, diameter 45 μm) at a temperature T2 into a plexiglass expansion chamber which contained a 4% by weight aqueous solution of the emulsifier or protective colloid. The fluid medium evaporated and the dispersed nanoparticles enclosed in the protective colloid remained. The process conditions and the mean particle size range (determined photometrically by the 3-WEM method) are given in Table 1 below.

Table 1

Nanoparticles

*) 58.1% by weight of β-sitosterol, 29.8% by weight of campesterol, 4.5% by weight of stigmasterol; 3.8 wt% tocopherol; 0.4% by weight cholesterol; 0.3 wt% squalane; ad 100 unsaponifiable.

Claims

claims

1. Process for the production of nanoparticles with diameters in the range from 10 to 300 nm, in which

(a) dissolving organic active substances in a solvent under supercritical or near-critical conditions,

(b) the fluid mixture is expanded into a gas or liquid via a nozzle, and

(c) the solvent evaporates at the same time,

characterized in that emulsifiers and / or protective colloids are also used.

2. The method according to claim 1, characterized in that active substances are used which are selected from the group formed by sterotes, antioxidants, flavones, waxes, fatty acids, fatty alcohols, metal soaps, dyes, UV light protection factors, fragrances, enzymes and Enzyme inhibitors and cosmetic ingredients solid at room temperature and their mixtures is formed.

3. Process according to claims 1 or 2, characterized in that supercritical carbon dioxide is used as the solvent.

4. The method according to at least one of claims 1 to 3, characterized in that the active ingredients are dissolved at temperatures in the range from 40 to 100 ° C and pressures in the range from 20 to 200 bar.

5. The method according to at least one of claims 1 to 4, characterized in that the active ingredients are dissolved in the presence of emulsifiers and / or protective colloids and their solutions in water, alcohols or cosmetic oils.

6. The method according to at least one of claims 1 to 5, characterized in that one relaxes the fluid mixtures in aqueous and / or alcoholic solutions of emulsifiers and / or protective colloids or mixtures thereof with cosmetic oils.

7. Process according to claims 5 or 6, characterized in that emulsifiers are used which are selected from the group formed by addition products of 2 to 30 mol of ethylene oxide and / or 0 to 5 mol of propylene oxide with linear fatty alcohols with 8 up to 22 C atoms, on fatty acids with 12 to 22 C atoms and on alkylphenols with 8 to 15 C atoms in the alkyl group; Ci∑yiβ fatty acid monoesters and diesters of adducts of 1 to 30 moles of ethylene oxide with glycerol; Glycerol monoesters and diesters and sorbitan monoesters and diesters of saturated and unsaturated fatty acids having 6 to 22 carbon atoms and their ethylene oxide addition products; Alkyl mono- and oligoglycosides with 8 to 22 carbon atoms in the alkyl radical and their ethoxylated analogs; Addition products of 15 to 60 mol of ethylene oxide with castor oil and / or hardened castor oil; Polyolester; Addition products of 2 to 15 mol of ethylene oxide with castor oil and / or hardened castor oil; Partial esters based on linear, branched, unsaturated or saturated Cε / 22 fatty acids, ricinoleic acid and 12-hydroxystearic acid and glycerol, polyglycerol, pentaerythritol, dipentaerythritol, sugar alcohols, alkyl glucosides and polyglucosides; Mono-, di- and trialkyl phosphates and mono-, di- and / or tri-PEG-alkyl phosphates and their salts; Wool wax alcohols; Polysiloxane-polyalkyi-polyether copolymers; Mixed esters of pentaerythritol, fatty acids, citric acid and fatty alcohol and / or mixed esters of fatty acids with 6 to 22 carbon atoms, methyl glucose and polyols; and polyalkylene glycols.

Process according to claims 5 or 6, characterized in that protective colloids are used which are selected from the group consisting of gelatin, casein, gum arabic, lysalbic acid, starch polyvinyl alcohols, polyvinyl pyrrolidones, polyethylene glycols and polyacrylates.

Process according to at least one of Claims 5 to 8, characterized in that the emulsifiers and / or protective colloids are used in amounts of 0.1 to 20% by weight, based on the active ingredients.