EP2034961A1

EP2034961A1 - Solubilisate formulations

Info

Publication number: EP2034961A1
Application number: EP07728370A
Authority: EP
Inventors: Gertrud Langhoff
Original assignee: Individual
Current assignee: Individual
Priority date: 2006-06-30
Filing date: 2007-04-20
Publication date: 2009-03-18
Also published as: WO2008000534A1

Abstract

The invention relates to liquid, watery, micellar emulsions containing one or several phospholipids, a micellar stabilizer consisting of carnitine, and/or a physiologically compatible carnitine derivative, and/or polyolene, as well as a scavenger, selected from the group consisting of ascorbic acid, and/or alkaline, and/or alkaline earth salts of ascorbic acid, and/or an ester of one or several organic acids with ascorbic acid, and/or physiologically compatible derivatives of ascorbic acids. The invention further relates to a method for producing solid compounds as well as cosmetic, or pharmaceutical, or dietetic formulations that contain an emulsion, or a powder produced therefrom, or such a compound, as an additive. The invention further relates to drinks, boiled sweets, and chewing gum containing the emulsion, or the powder produced therefrom.

Description

Solubilisatformulierunqen

The invention relates to liquid, aqueous micellar emulsions comprising one or more phospholipid (s), a micelle stabilizer consisting of carnitine and / or a physiologically tolerated carnitine derivative and / or polyols, and a radical scavenger selected from the group consisting of ascorbic acid and / or alkali metal and / or alkaline earth metal salts of ascorbic acid and / or esters of one or more organic acid (s) with ascorbic acid and / or physiologically acceptable derivatives of ascorbic acid. Furthermore, the invention relates to a process for the preparation of solid compositions and to cosmetic or pharmaceutical or dietetic formulations which contain an emulsion or a powder produced therefrom or use such a composition as an additive. Furthermore, the invention relates to drinks, lozenges and chewy masses containing the emulsion or a powder produced therefrom.

In particular, in the field of pharmaceutical technology, dietetics and cosmetic formulations there is a great need to formulate active ingredients or drug combinations and decomposition-sensitive components of the respective formulations long-term stable, but at the same time, especially in pharmaceutical and dietary formulations, the physiological compatibility of the overall formulation must be guaranteed , In many cases, the incorporation of suitable preservatives proves to be problematic, which is inadequate especially in the case of lipophilic components due to the difficult solubility ratios.

The state of the art is that the solubilization of fatty substances to transparent systems in the above-mentioned applications exclusively with ethoxylated surfactants or surfactant systems which have a high HLB value and / or alcohol can be accomplished. However, these solubilizers have significant disadvantages. For example, volatile alcohols, such as, for example, ethanol, propan-1-ol or isopropanol, are potent cell poisons. Alkoxylated surfactants, on the other hand, are physiologically incompatible and unsuitable in particular for pharmaceutical and dietetic formulations. In addition, the alkoxylated surfactants must be used in the prior art in a large amount, so that the production of concentrates is extremely difficult.

DE 102 55 195 A1 describes micellar water-soluble concentrates of fatty substances with the aid of combinations of phospholipids or lecithins and highly concentrated aqueous solutions of polyols or carbohydrates, the concentration of the polyol or carbohydrate solutions being between 30 and 99% by weight, the ratio of lecithin to lipid between 1: 1 and 1:10 and the concentration of the lecithin / lipid mixture in the polyol or carbohydrate solution is between 10% and 90% by weight. The formulations disclosed in DE 102 55 195 A1 have very high amounts of carbohydrates, in particular fructose. This results in carbohydrates, in particular fructose, considerable physiological disadvantages, in particular as regards the use in the field of pharmaceutical technology and dietary formulations. The formulations described do not provide the substances to be solubilized with adequate protection against attack by radicals and against enzymatic decomposition, as may occur especially in aqueous solutions. In particular, the long-term degradation of fatty acids in phosphatidylcholine by free-radical processes is taken into account in the formulation. In addition, the formulations disclosed in DE 102 55 195 Al lead the body to large amounts of sugar. Of particular concern is the use of fructose. Fructose is taken insulin-independently in the body and metabolized in the cells by phospholiprolytes once as fast as glucose. newer Studies have shown that after eating fructose, large amounts of fats are produced in the liver and passed on to the blood. The large blood lipid levels to be detected in the population are often causally linked to a high intake of fructose-containing foods. These mainly include granulated sugar (sucrose). It is therefore necessary to minimize the content of fructose in pharmaceutical or dietetic products. In addition, over-consumption of fructose is believed to increase cholesterol. Furthermore, high fructose intake causes calcium uptake in the body to be disturbed. Since fructose can be rapidly broken down into pyruvic acids in the body, there are also indirect problems with calcium absorption. The use of products with a high fructose content, for example in dietetics or pharmacy, may thus have adverse consequences for the consumer in the long term also with regard to the calcium balance. DE 102 55 195 Al expressly dispenses with a further use of preservatives.

WO 2006/042574 A2 discloses solubilizate formulations consisting of an aqueous solution of alkali metal and / or alkaline earth metal salts of ascorbic acid and an emulsifier having an HLB value of 9 to 18, in particular polysorbate for foods, cosmetics and the like.

EP-A2-0 206 240 discloses solid pharmaceutical compositions containing carnitine, lecithin and other common additives. The solid formulations are processed into chewable tablets.

US-B1,573,299 discloses topically applied gels and creams. However, the formulations are neither a micellar emulsion with an average micelle size of 3 to 250 nm, nor are the gels and creams disclosed transparent. US-5,922,331 discloses a skin cream composition comprising water, long-chain fatty acid esters of ascorbic acid, short-chain carboxylic acid esters of tocopherol and a glyceryl ester complex, as well as several other complexes of widely varying composition.

The formulations disclosed in the prior art also have the disadvantage that the absorption rate of the solubilized active ingredients is too low, the solubilization can not be carried out with sufficiently high concentrations of active ingredient or the physiological compatibility is not guaranteed.

The object of the present invention is to provide long-term stable emulsions which are suitable for effectively solubilizing hydrophilic as well as in particular lipophilic substances, at the same time enabling a high physiological compatibility as well as rapid absorption of the composition by the body.

In addition, it was an object of the present invention to provide readily handleable solid compositions and liquid emulsions, as well as an effective, energy-saving and gentle process for producing such solid compositions.

Surprisingly, it has now been found that a liquid, aqueous micellar emulsion containing a) one or more phospholipid (s), b) a micelle stabilizer consisting of carnitine and / or a physiologically acceptable carnitine derivative and / or polyol (s), and c ) a radical scavenger selected from the group consisting of ascorbic acid and / or alkali and / or alkaline earth metal salts of ascorbic acid and / or esters of one or more organic acid (s) with ascorbic acid and / or physiologically acceptable derivatives of Ascorbic acid, wherein the micelles have a mean diameter of 3 to 250 nm, solve the aforementioned problems.

As an essential constituent, the aqueous, micellar emulsions according to the invention comprise one or more phospholipid (s). Phospholipids are phosphoric diesters or monoesters which, owing to their fat-like solubility properties, are expected to be lipids due to the lipophilic and hydrophilic components and are involved in the organism as membrane lipids in the construction of layer structures of the membrane. Phospholipids are particularly abundant in the brain and myelin. A particular group of phospholipids derived from sphingosine are the so-called phosphosphingolipids. However, the compositions of the invention preferably contain phospholipids which are derivatives of glycerol and are also referred to as phosphoglycerides or phosphatides.

In lipid nomenclature, so-called stereospecific numbering (abbreviation: sn-, according to IUPAC / IUBMB rule Lip-1.13) has proved to be useful for asymmetric glycerol derivatives, in which the (free or substituted) hydroxy group is in position 2 of the glycerol part pointing to the left and the geminal hydrogen atom drawn to the right and thought to be projecting beyond the plane of the paper, whereupon the carbon atom 1 of the glycerol part is directed upwards, carbon atom 3, however, downwards.

Formula 1 :

³ ^ CH ₂ -OR ³

Phosphatidic acids are glycerol derivatives which in 1-sn- and 2-position with fatty acids (1-sn-position: mostly saturated, 2-position: usually mono- or polyunsaturated), on atom 3-sn, however, esterified with phosphoric acid (Formula 1: Rl, R2 = acyl, R3 = phosphoryl). The phosphatidic acids themselves probably have cytoskeletal, membrane transport, and secretion regulatory functions, are released by phospholipase D from phosphatides, and are found only in small amounts in the tissue; Their phosphate residue is mostly esterified with aminoalcohols such as choline (lecithin = 3-sn-phosphatidylcholine) or 2-aminoethanol (ethanolamine) or L-serine (cephalin = 3-sn-phosphatidylethanolamine or -L-serine), with myo Inositol to the phosphoinositides [l- (3-sn-phosphatidyl) -D-myo-inositol], which are common in tissues, with glycerol to the phosphatidylglycerols detected in the amniotic fluid, which are also found in the protein export from Gram-neg. Bacteria should play a role. Cardiolipins (1,3-bisphosphatidylglycerols) are phospholipids isolated from mitochondrial membranes of the heart muscle and composed of two glycerol-linked phosphatidic acids. Lysophospholipids are obtained when phospholipids cleave an acyl (fatty acid) residue by phospholipase A; Example: lysolecithins. Phosphatases and the like Phosphodiesterases such as phospholipases C and D, on the other hand, cleave phospholipids on the phosphate bonds. The phospholipids also include the plasmalogens, in which instead of a fatty acid in the 1-position, an aldehyde (in the form of an enol ether) is bound; the phosphatidylcholines corresponding O-1-sn-alkenyl verb. z. B. called Phosphatidalcholine. From the name plasmalogen, the collective name plasmenic acids derived phospholipids with an enol ether group in 1-, one (unsaturated) acyl group in 2- and one Phosphoric acid group in the 3-position; the corresponding 1-alkyl ether derivatives are called plasmic acids and desacylated derivatives, for example lysoplasmenylserine. Another phospholipid is the platelet-activating factor (PAF, see formula 1 with R 1 = octadecyl, R 2 = acetyl and R 3 = phosphorylcholine). In ciliate membranes, phosphonolipids have been discovered that may function to facilitate survival in the presence of self-secreted phospholipases.

Phosphatidyl-L-serines and phosphatidylinositols are formed by enzymatic reaction of L-serine or myo-inositol with 3-CDP-1,2-diacyl-sn-glycerols to release cytidine-5'-monophosphate. Phosphatidylethanolamines are formed by decarboxylation of phosphatidyl-L-serines, phosphatidylcholines in turn by stepwise methylation of ethanolamine derivatives. On the other hand, released choline and ethanolamine can be activated with the aid of cytidine-5'-triphosphate to the CDP derivatives and then react with 1,2-diacyl-sn-glycerols with cleavage of CMP to the corresponding phosphoglycerides.

The emulsions according to the invention particularly preferably contain lecithin as phospholipid. Lecithin is the group name for those glycerophospholipids which are formed from fatty acids, glycerol and phosphoric acid and choline by esterification. Today, the name phosphatidylcholine has largely prevailed.

Formula 2:

X

AIIg. Structure of lecithins; R1, R2: typically unbranched aliphatic radicals having 15 or 17 carbon atoms and up to 4 cis double bonds.

The naturally occurring lecithins, like the closely related cephalins, are derivatives of 1,2-diacyl-sn-glycerol-3-phosphoric acids (phosphatidic acids, X = H, R2-CO-O- in Fischer projection pointing to the left). So have α configuration. In the case of β-lecithin, the phosphoric acid residue esterified with choline is bound to the mediate hydroxyl group of a glyceride. The diversity of the fatty acid residues R 1 and R 2 results in a large number of different lecithins. Extractions of biological material always give mixtures. For example, a soybean lecithin fraction contains palmitic acid, stearic acid, palmitoleic acid, oleic acid, linoleic acid and linolenic acid. Normally, the saturated fatty acid is esterified with the primary, the unsaturated with the secondary hydroxy group of glycerol.

In a preferred embodiment of the present invention, the emulsions according to the invention comprise phospholipid which has been obtained from soybean and / or oilseed rape and / or egg.

More preferred is phospholipid derived from rapeseed, fish or milk. More preferably, the emulsions according to the invention contain hydrogenated and / or hydrolyzed and / or hydroxylated phospholipids.

Particular preference is given to emulsions according to the invention which contain lecithin, in particular soya and / or egg lecithin.

The phospholipid (s) are preferably present in the emulsions according to the invention in an amount of from 0.4 to 50% by weight, more preferably from 0.7 to 40% by weight, particularly preferably from 2 to 20% by weight. and in particular from 2.5 to 15 wt .-%, especially from 4 to 10 wt .-% and most preferably from 4 to 6 wt .-%, each based on the total emulsion before.

Another essential constituent of the composition according to the invention is a radical scavenger selected from the group consisting of ascorbic acid and / or alkali and / or alkaline earth salts of ascorbic acid and / or esters of one or more organic acids with ascorbic acid and / or physiologically tolerable Derivatives of ascorbic acid. The compositions according to the invention preferably contain alkali metal and / or alkaline earth metal salts of ascorbic acid. In this case, radical scavengers selected from the group consisting of sodium ascorbate or potassium ascorbate are particularly preferred. In a further preferred embodiment, the compositions according to the invention comprise esters, preferably monoesters, of organic acids with ascorbic acid. In a preferred embodiment, the radical scavenger is a C ₈ -C ₃₀ - fatty acid ester, preferably C ₈ -C ₃ o-Fettsäuremonoester, more preferably Ci ₂ -C ₂₂ -Fettsäuremonoester, the ascorbic acid, particularly preferably imitation thereof Ascorbylpa or ascorbyl stearate, or any mixtures thereof.

The construction of particularly stable aqueous micellar emulsions in the required nanoscale micelle range has been found to be optimal with the use of sodium or potassium ascorbate. The radical scavenger is in a particular embodiment in an amount of 4 to 50 wt .-%, more preferably from 5 to 45 wt .-% and in particular from 7 to 30 wt .-%, each based on the total emulsion before ,

As a further essential ingredient, the emulsion of the invention contains a micelle stabilizer consisting of carnitine and / or a physiologically acceptable carnitine derivative and / or polyol (s).

Carnitine (3-hydroxy-4- (trimethylammonio) butyric betaine) forms colorless hygroscopic crystals and is readily soluble in water. The L-form of carnitine is widely distributed in animal tissues and is a characteristic component of the striped musculature. In a preferred embodiment, the compositions of the invention contain L-carnitine and / or carnitine derivatives selected from L-carnitine tartrate or acetyl-L-carnitine.

Polyols in the context of the present invention include all organic molecules which have at least 2, preferably at least 3 hydroxyl groups. Furthermore, in the context of the present invention, the radical scavenger to be used according to the invention is selected from the group consisting of ascorbic acid and / or alkali and / or alkaline earth salts of ascorbic acid and / or esters of one or more organic acids with ascorbic acid and / or physiologically tolerated derivatives ascorbic acid, not a polyol. The compositions according to the invention preferably contain aliphatic polyols having alkyl chain lengths which comprise 3 to 10, particularly preferably 3 to 6, carbon atoms. In a preferred embodiment, the polyol is selected from the group of C ₃ -C ₆ -di-, -tri-, -tetra-, -penta- or -hexaols, preferably glycerol, pentite, more preferably xylitol or hexitol, in particular sorbitol, Mannitol, gulitol or inositol. The emulsions according to the invention preferably comprise one or more polyol (s) selected from the group consisting of glucose, chodroitin sulfate, glucosamine sulfate, glycerol, mannitol and sorbitol.

In a further preferred embodiment, the polyol is selected from the group of carbohydrates, preferably monosaccharides, disaccharides and / or oligosaccharides, in particular mannitol, maltodextrin, glucose, glucose and / or pectin and / or its physiologically acceptable derivatives.

Preferred emulsions according to the invention are essentially free from fructose, the fructose content is preferably below 5% by weight, more preferably below 2% by weight, in particular below 1% by weight, further preferably below 0.05 Wt .-%, each based on the total emulsion. Special emulsions according to the present invention are free of fructose.

The carnitine and / or a physiologically acceptable carnitine derivative is in a preferred embodiment in an amount of 1 to 60 wt .-%, preferably from 3 to 55 wt .-%, particularly preferably from 4 to 45 wt .-% and in particular from 5 to 25 wt .-%, each based on the total composition in the emulsions according to the invention before.

The polyol (s) are preferably present in an amount of from 3.5 to 60% by weight, preferably from 20 to 60% by weight and in particular from 25 to 45% by weight, based in each case on the entire emulsion, in front.

The liquid, aqueous micellar emulsions according to the present invention preferably have a pH of from 4.0 to 9.5, in particular from 6.0 to 8.0. The water content of the liquid aqueous emulsions in a preferred embodiment is from 0.1 to 81% by weight, preferably from 3 to 75% by weight and in particular from 8 to 30% by weight, in each case based on the total aqueous emulsion, in front.

The liquid aqueous emulsions of the invention form micelles which are particularly suitable for solubilizing lipophilic substances. The formation of micelles also makes it possible to produce concentrated liquid formulations which, for example, have a water content below 40% by weight. In a preferred embodiment, the liquid aqueous emulsions are present as a micellar concentrate. The micelles in the emulsions according to the invention preferably have an average diameter of from 10 to 120 nm, preferably from 20 to 100 nm, in particular from 50 to 80 nm. The liquid aqueous emulsions according to the present invention are preferably transparent.

The mean diameter of the micelles can be determined by methods familiar to those skilled in the art, for example a Coulter Counter N24.

Specially suitable emulsions according to the invention, which ensure particularly rapid absorption of solubilized active ingredients and, moreover, give particularly stable emulsions according to the invention and also transparent emulsions are emulsions containing 4 to 6% by weight of lecithin, 25 to 45% by weight of glucose, 7 to 30% by weight % Of sodium and / or potassium ascorbate, 0 to 20% by weight, preferably 5 to 15% by weight of carnitine, the percentages by weight being based on the total emulsion.

Furthermore, the emulsions according to the invention may have flavors and flavorings. This is particularly important for the use of the emulsions in the food industry, for example as a beverage, or in pharmaceutical formulations. The solubilization of caffeine and / or taurine with the emulsions according to the invention is excellent and provides emulsions which may contain these active ingredients, wherein the small micelle size of the emulsion remains stable and provides rapid drug availability.

The incorporation of taurine and / or caffeine-containing emulsions according to the invention is particularly suitable in beverages and in other foods.

The emulsions according to the invention are distinguished by particularly good physiological compatibility. In a preferred embodiment, the emulsions of the invention below 5 wt .-%, preferably below 2.5 wt .-%, more preferably below 1 wt .-% Ci-CrMonoalkohole on. In particular, however, they are substantially free of C 1 -C ₄ -monoalcohols, in particular substantially free of ethanol or C ₃ -monool and / or substantially free of artificial surfactants or emulsifiers, in particular substantially free of alkoxylated alcohols, acids or amines. In a specific embodiment, the emulsions are free of C 1 -C ₄ -monoalcohols and / or artificial surfactants or emulsifiers or alkoxylated alcohols, amines or acids.

The emulsions according to the invention are characterized in that they are capable of solubilizing in particular lipophilic substances. By incorporating lipophilic substances, these can not only be solubilized in an aqueous system, but can also be excellently stabilized and protected against enzymatic and oxidative attacks. In principle, lipophilic substances of any kind, in particular substances which are used in pharmaceutical technology, pharmacy, pharmacology, dietetics and cosmetics, can be incorporated into the emulsions according to the invention. In a preferred embodiment, the emulsions according to the invention therefore additionally comprise one or more lipophilic (n) solubilizable (s) substance (s) selected from the group of C ₀ -C ₃₀ - fatty acids, waxes or their esters, paraffins, C ₀ -C ₃₀ fatty alcohols, C ₀ -C ₃₀ - fatty aldehydes, triglycerides, Oils, isoprenoids, terpenes, citral, menthol camphor, bisabolol, cholesterol or its derivatives, vitamin D, testosterone, estrogen, progesterone, cortisol, aldosterone and their respective physiologically acceptable / acceptable derivatives, ethinylestradiol, sitosterols, vitamin A, vitamin K, vitamin E, tocopherols, tocotrienols, carotenoids, beta-carotene, lutein, zeaxanthin or their physiologically tolerated derivatives, coenzyme Q10 and polar lipids, ceramides, sphingilipids, glycolipids, amines, amino acids, peptides or their derivatives, silicone oils and lipophilic UV-A and UV -B filter.

The lipophilic solubilisable substances preferably have an HLB value of less than 10. The HLB value is determined by the method of Griffin (Griffin, W.C.: Classification of surface active agents by HLB, J. Soc., Cosmet., Chem., 1, 1949).

The emulsions according to the invention have proven particularly suitable for the solubilization and stabilization of vitamins and pharmaceutically active substances which can be administered in liquid form and further processed in solid form. The emulsion of the invention has the additional advantage that due to the particle size of the micelles, the vitamins or pharmaceutical active ingredients can be absorbed very well and quickly. As such, the emulsions according to the invention can already be in the galenic form or can be added to a galenic formulation in a further step.

The emulsions according to the invention preferably contain a pharmaceutical active substance.

In a preferred embodiment, the emulsions according to the invention additionally comprise at least one member selected from the group containing melatonin, 5-hydroxytryptophan, tryptophan, serotonin, tyrosine, dopamine or L-dopa.

In a further embodiment, the composition according to the invention additionally contains vitamins selected from the B series.

Preferred vitamins are thiamine (Bi), riboflavin (B ₂ ), nicotinamide, nicotinic acid (niacin - B ₃ ), pantothenic acid (B ₅ ), pyridoxal (B ₆ ), cobalamin (Bi ₂ ), folic acid, biotin (vitamin H) and / or their physiologically tolerated derivatives.

The emulsions of the invention preferably additionally contain one or more amino acids selected from the group consisting of glycine, alanine, leucine, isoleucine, valine, lysine, methionine, phenylalanine, threonine, arginine, cysteine, glutamate, serine, taurine, asparagine, glutamic acid, ornithine and proline ,

Furthermore, the emulsions may additionally contain glutathione or creatine as well as a combination of lipoic acid and para-aminobenzoic acid.

Further preferably, the emulsion according to the invention additionally contains minerals and / or trace elements. Suitable minerals and trace elements are potassium, calcium, e.g. as calcium gluconate, magnesium, sodium, selenium e.g. as sodium selenite, zinc e.g. as zinc gluconate, iron e.g. as iron gluconate, iodine, e.g. as potassium iodide, fluorine e.g. as sodium fluoride, chromium e.g. as chromium III chloride, copper e.g. as copper gluconate, manganese e.g. as manganese gluconate, molybdenum, boron e.g. as boraspartate, vanadium e.g. as vanadyl sulfate and / or other physiologically acceptable derivatives.

Furthermore, the solubilisable substance is preferably selected from the group of non-steroidal analgesics and / or antirheumatics. Particularly suitable for solubilization are the non-steroidal ones Analgesics and / or antirheumatics selected from the group comprising aceclofenac, acemetacin, acetylsalicylic acid and their physiologically tolerated derivatives such as DL-lysine monoacetylsalicylate), dexibuprofen, auranofin, nettle leaf dry extract, celecoxib, dexketoprofen trometamol, diclofenac and their physiologically acceptable derivatives such as diclofenac , Diclofenac Na, diclofenac potassium and diclofenac colestyramine, etanercept, etofenamate, etoricoxib, glucosamine sulfate, hyaluronic acid and their physiologically tolerated derivatives such. As sodium hyaluronate, ibuprofen and their physiologically acceptable derivatives such as ibuprofen-DL-lysinate, indomethacin, ketoprofen, leflunomide, lornoxicam, meloxicam, metamizole and their physiologically acceptable derivatives such as metamizole sodium, methotrexate and their physiologically acceptable derivatives such as methotrexate Di-sodium, nabumetone, naproxen and their physiologically acceptable derivatives such as naproxen sodium, nicoboxil, nonivamide, oxaceprol, oxaprozin, paracetamol, penicillamine, phenazone, phenylbutazone, piroxicam, proglumetacin, and their physiologically acceptable derivatives such as proglumetacin di maleate, propyphenazone Salicylic acid and its physiologically acceptable derivatives such as hydroxyethyl salicylate, sodium salicylate, sulfasalazine, devil's claw dry extract, tiaprofenic acid, valdecoxib, methylsulfonylmethane and / or willow bark extract proven.

Furthermore, the solubilisable substance is preferably selected from the group of steroidal analgesics and / or antirheumatics. For this purpose, the steroidal analgesics and / or antirheumatics selected from the group comprising morphine and their physiologically tolerated derivatives such as morphine hydrochloride, morphine sulfate, codeine and their physiologically tolerated derivatives such as eg codeine sulfate, codeine phosphate and / or dihydrcodeine have proved to be particularly suitable for the solubilization. In addition, (partial) synthetic analgesics are preferred. In particular, those with structural elements of morphine selected from the group hydromorphone and their physiologically acceptable derivatives such as hydromorphone hydrochloride, buprenorphine and their physiological compatible derivatives such as buprenorphine hydrochloride, fentanyl, flupirtine, levomethadone and their physiologically acceptable derivatives such as levomethadone hydrochloride, oxycodone, tramadol and their physiologically acceptable derivatives such as tramadol hydrochloride, tilidine and their physiologically acceptable derivatives such as tilidine hydrochloride and / or naloxone and their physiologically acceptable derivatives such as naloxone hydrochloride.

Further preferably, the solubilizable substance is selected from the group of antihistamines. For this purpose, the antihistamines selected from the group comprising chlorphenoxamine and their physiologically tolerated derivatives, such as, for example, are particularly suitable for solubilization. Chlorphenoxamine hydrochloride, Dimetinden and their physiologically acceptable derivatives such. Dimetindmaleate, triplenamine and their physiologically acceptable derivatives such as e.g. Triple amine hydrochloride and / or clemastine and their physiologically acceptable derivatives such as e.g. Clemastin hydrogen fumarate and citrizine, such as citrizine hydrochloride proved.

Furthermore, the solubilisable substance is preferably selected from the group of local anesthetics. For this purpose, the local anesthetics selected from the group comprising benzocaine and their physiologically tolerated derivatives, such as, for example, are particularly suitable for solubilization. Benzocaine hydrochloride, lidocaine and their physiologically acceptable derivatives such. such as lidocaine hydrochloride and / or procaine and their physiologically acceptable derivatives such as e.g. Procaine hydrochloride proved.

Further preferably, the solubilizable substance is selected from the group of alkaloids. For this purpose, the alkaloids selected from the group comprising nicotine and their physiologically tolerated derivatives, such as, for example, nicotine hydrochloride, scopolamine and their physiologically tolerated derivatives, such as, for example, have proven particularly suitable for solubilization Scopolamine. Ephedrine and their physiologically acceptable derivatives such as ephedrine hydrochloride and / or pseudoephedrine and their physiologically acceptable derivatives such as pseudoephedrine hydrochloride proved.

Further preferably, the solubilisable substance is selected from the group of anticoagulants. Anticoagulants selected from the group comprising heparin and their physiologically tolerated derivatives, such as, for example, heparin-Na, horse chestnut dry extract and / or flavonoids, such as, for example, are particularly suitable for solubilization. Rutin proved.

Furthermore, the solubilisable substance is preferably selected from the group of antimycotics. To this end, the antifungals selected from the group consisting of bifonazole, croconazole and their physiologically tolerated derivatives such as, for example, croconazole hydrochloride, clotrimazole, ciclopirox and their physiologically tolerated derivatives such as, for example, ciclopirox-olamine, econazole and their physiologically tolerated derivatives such as, for example, are particularly suitable for solubilization Econazole nitrate, fluconazole, isoconazole and their physiologically acceptable derivatives such as isoconazole nitrate, itraconazole, ketoconazole, miconazole and their physiologically acceptable derivatives such as Miconazole nitrate, oxiconazole and their physiologically acceptable derivatives such as Oxiconazolnitrat, sertaconazole and their physiologically acceptable derivatives such as Sertaconazolnitrat, Tioconazol and / or Tolnaftat proven.

Furthermore, the emulsions according to the invention may contain parasympathomimetics, for example neostigmine, pyridosigmine or parachol or sympathomimetics selected from the group consisting of adrenaline, norepinephrine, ephedrine, isoprenaline or solbutanol and also parasympatholytics selected from the group comprising atropine, scopalamine or butylscopalamin. In particular, the emulsions according to the invention with active ingredients selected from the group comprising diclofenac, acetylsalicylic acid, ibuprofen, testosterone, coenzyme Q 10, thiamine, riboflavin, niacin, pyridoxine, taurine and caffeine have markedly improved physiological uptake into the cells, in particular via the small intestinal mucosa, as well transdermal, shown.

The emulsions according to the invention may additionally contain purines, in particular selected from the group consisting of caffeine, theophylline and theobromine.

The solubilisable substance is furthermore preferably an alkaloid, preferably selected from the group consisting of nicotine, nicotine hydrochloride, scopolamine, scopolamine hydrochloride, atropine, atropine hydrochloride, ephedrine, ephedrine hydrochloride, pseudoephedrine, pseudoephedrine hydrochloride and in each case their physiologically tolerated derivatives.

The additional solubilisable substances are present in the emulsions according to the invention in an amount of from 0 to 50% by weight, preferably from 1 to 35% by weight, more preferably from 3 to 30% by weight and in particular from 5 to 25% by weight. %, in each case based on the total emulsion.

The preparation of the liquid aqueous emulsions according to the present invention takes place in a so-called one-pot process, in which the components of the composition according to the invention are stirred in water and mixed. Depending on the composition, the mixing can be treated with stirring tools familiar to the person skilled in the art or with high-shear devices which are familiar to the person skilled in the art. Preference is given to the use of Ultraturax devices or high-pressure homogenizers. For the preparation of transparent liquid formulations, the homogenization by means of a high pressure homogenizer has been found to be particularly suitable. In particular, for the processing of the emulsions of the invention to dried powders, the addition of inorganic or organic acids and / or salts thereof or else the addition of starch has been found to be particularly suitable. In a preferred embodiment, the compositions according to the invention therefore additionally comprise an inorganic or organic acid and / or salts thereof, preferably selected from the group comprising citric acid, gluconic acid, calcium, magnesium, sodium and / or potassium citrate, calcium, magnesium , Potassium or sodium gluconate, sodium or calcium bicarbonate or hydrogen phosphate.

A significant advantage of the emulsions according to the invention is that they are easy to process into solids. In contrast to conventional systems, finely divided powders can be produced with the emulsions according to the invention, so that it is not only possible to provide solubilisable substances, in particular lipophilic substances, in a stable and oxidation-resistant manner in a high concentration, but at the same time a suitable and good handling is provided. The solids produced from the emulsions according to the invention are present in particular as powder or granules or as pressed molded bodies. The powders have an average particle size of 0.1 to 5000 .mu.m, preferably from 100 to 800 .mu.m. The average particle size of the powders was measured with a Coulter counter.

Pressed shaped articles, such as tablets, for example, can contain the additional components known to the person skilled in the art, such as disintegrating agents.

In particular, when the emulsions according to the invention additionally contain temperature-sensitive active substances, the spray-drying process for recovering the solid has proven particularly suitable. Preferably, the invention Compositions therefore as a spray-dried solid, preferably as a spray-dried powder.

Another object of the present invention is a process for the preparation of a solid composition, wherein a liquid aqueous micellar emulsion according to the invention is spray-dried.

For spray drying, commercially available spray drying devices can be used. For this purpose, the liquid aqueous emulsions according to the present invention are fed to the spray-drying apparatus and sprayed in the apparatus. Spray drying is a continuous process for drying solutions, suspensions or pasty materials. By means of a nozzle (operated by liquid pressure or compressed air or inert gas) or rotating atomizing disks (400-50000 rpm), the material to be dried is introduced into a drying gas stream which dries it to a fine powder in fractions of a second. The drying can flow in the direction of the spray jet or against the spray jet (DC, countercurrent process), depending on the design or intended use. The spray is preferably located at the top of a spray tower, the resulting dry material is usually separated by a cyclone from the air flow and can be removed there. The aqueous emulsion according to the invention is preferably introduced into the spray-drying apparatus at the upper end of a spray-drying tower via spray nozzles. The spray drying is preferably carried out by passing gas from a lower portion of the spray drying tower through the drying tower. The spray drying is preferably carried out at a dry gas temperature of 5 to 200 ⁰ C, preferably at 30 to 120 ⁰ C. The spray drying process is a particularly gentle process by which the solid compositions according to the invention can be obtained economically but also stable and without damage. It has been found that powdery or granular products of the composition according to the invention, in particular spray-dried solids of the inventive Composition, can be prepared by a spray drying process, which is operated by the spouted technology. The basis of the spouted bed technology is the fluidization of particles by upward flowing dry gas (process gas). Unlike fluidized bed processes, the air does not enter the process chamber from below through a sieve bottom, but rather through longitudinal gaps in the lower area. In an advantageous embodiment of the method according to the invention, the cross section of the process chamber of the spray drying device is significantly widened upwards. As a result, the flow velocity in the process chamber drops sharply. Preferably, the drying gas is introduced laterally by longitudinal gaps in the process chamber. The gap width can be adjusted for example by roller-shaped arrangements. Depending on the size of the spray dryer and the dry gas pressure, the gap width can vary over a wide range. The gap width is preferably 0.2 to 200 mm, more preferably 0.3 to 100 mm, in particular 0.4 to 60 mm, for example 0.4 to 55 mm. In a further preferred embodiment of the method according to the invention are located above the Trockenzaseinströmspalts plates, which are preferably arranged regularly on both sides of the gap, so that the width of the Trockengaseinströmspaltes is further narrowed by the plates. The drying gas is not guided exclusively through the remaining gap, but can flow according to a preferred embodiment by recessed into the plates channels. The channels are advantageously holes in the plates, which are preferably embedded with a different angle with respect to the main flow direction through the gap in the plates. Preferably, the linear channels in the plates at an angle of 0 to 75 °, preferably 10 to 65 °, more preferably 20 to 55 ° and in particular 30 to 50 °, for example 45 °, wherein 0 ° is parallel to the main flow direction through the gap and 90 ° parallel to the longitudinal orientation of the plate. The dry gas channels in the plates can be arranged regularly or advantageously irregular. The obliquely embedded dry gas channels in the plates have the advantage that the Drying gas flowing against the plates can flow via the channels into the process chamber of the spray dryer. It has surprisingly been found that this arrangement of the spray dryer is a very gentle drying for the partially very temperature-sensitive products. It has been observed that the dry material cools more slowly and the spray-dried compositions produced according to the invention show a higher crystallinity and better flowability and thus a significantly improved applicability of the spray-dried compositions according to the invention. In a further preferred embodiment, the aforementioned plates are chamfered at their ends to the Trockengaseinströmspalt out, so that the cross-section is widened in the direction of the process chamber. This leads to an additional drop in the flow velocity in the process chamber and thus accelerates the advantageous properties of the method according to the invention. The plates are preferably made of metals or thermally-resilient plastics. Preferably, the plates are made of V4A steel. The material thickness and the number of channels in the plates depends on the designs of the spray dryer and the process chamber. The dry gas inflow gap remaining through the plates to be used according to the invention preferably has a gap width of 4 to 55 mm, more preferably of 6 to 40 mm, in particular of 10 to 35 mm.

In particular, for the process according to the invention for the preparation of the solid compositions, it has proven advantageous for the aqueous liquid emulsion according to the invention to be present together with a further aqueous formulation A containing an organic or inorganic acid or its salts, preferably a polycarboxylic acid salt, preferably citric acid salt , in particular calcium and / or magnesium citrate or a gluconic acid salt, in particular sodium, magnesium or calcium gluconate is supplied to the spray drying. In a preferred embodiment of the method according to the invention, the feed of the aqueous formulation A is carried out separately from the liquid emulsion according to the invention to be dried. For this purpose, the separate feed of the formulation A can be fed to the spray dryer via a second nozzle, which is arranged separately from the nozzle and injects the liquid emulsion according to the invention. The nozzles are advantageously arranged so that sufficient mixing of the liquid emulsion according to the invention with the aqueous formulation A takes place in the spray dryer. In a further embodiment, the injection of the aqueous formulation A and the liquid emulsion according to the invention can also take place via a single nozzle, wherein it has proved to be advantageous if the aqueous formulation A and the liquid emulsion according to the invention are first brought together via two separate feeds and then immediately is injected into the spray dryer.

The nozzles in the process area of the spray dryer can spray from top to bottom or from bottom to top. Preferably is sprayed by a central arrangement of the nozzles at the point of highest energy input.

The addition of the separate formulation A to the aqueous liquid emulsions of the invention during the spray-drying process has shown that particularly free-flowing, readily processable powders can be obtained.

Another object of the present invention is a solid, preferably a powder, which is obtainable from the process according to the invention.

It has surprisingly been found that the solids according to the invention upon addition of water again give the aqueous micellar emulsions according to the invention. It is believed that the gentle use of the spray-drying process, the extremely finely divided micellar structures maintains. The powders according to the invention rapidly dissolve in water and form the emulsions, without requiring a renewed expensive use of high-shear agitators.

The solids according to the invention, in particular powders or else the liquid emulsions according to the invention are particularly suitable for cosmetic or pharmaceutical or dietetic compositions. They can be used there as an additive in the overall formulation or already represent the entire cosmetic or pharmaceutical or dietetic composition.

Another object of the present invention is therefore a cosmetic or pharmaceutical or dietetic composition comprising a solid according to the invention or a liquid emulsion according to the invention.

In addition, another object of the present invention is the use of the solid according to the invention or the liquid emulsion according to the invention as an additive in cosmetic, pharmaceutical or dietetic formulations.

The emulsions of the present invention provide an excellent solubilization system for a variety of vitamins and particularly physiological substances used in foods.

Another object of the invention is a beverage containing the emulsion according to the invention or the solid according to the invention, in particular the powder.

In particular, caffeine and / or taurine-containing emulsions or powders according to the invention are suitable as a beverage or as an additive to beverages. The fast physiological availability leads to the Consumers of the drinks to quickly enter the desired effect.

Another object of the present invention are lozenges or chewy masses containing the emulsion according to the invention or the solid according to the invention.

Chewy masses, such as chewing gum or gelatinous, slowly dissolving in the mouth moldings can be soaked with the emulsions of the invention during the manufacturing process. The methods for introducing the emulsions into chewing masses are familiar to the person skilled in the art. Candies may also be obtained by incorporation of the emulsion or powder of the invention. Preference is given to candies which contain the liquid emulsion in the interior. H first 11 methods for this purpose are well known to those skilled in the field of food technology, for example, the methods for the production of chocolates can be adapted.

The inventive compositions or liquid formulations according to the invention are usually sold as single portions. Another object of the present invention is therefore a single portion containing a composition of the invention or a liquid formulation according to the invention. Preferably, the single portion is in the form of a capsule or ampoule. The individual portions according to the invention preferably contain the composition according to the invention in an amount of 0.1 to 100 g. When pulverulent compositions according to the invention are portioned into capsules, the amount of composition is preferably 0.1 to 0.75 g. If the aqueous liquid formulation according to the invention is portioned into ampoules, this is preferably present in an amount of from 5 to 100 g. EXAMPLES

Example 1 :

Micelle concentrate according to the invention:

Table 1: Liquid, micellar emulsion

Example 2 Micelle Concentrate According to the Invention

Table 2: Liquid micellar emulsion

Example 3 Micelle Concentrate According to the Invention

Table 3:

The micelle concentrates listed in Examples 1 to 3 are homogenized in a high-pressure homogenizer (Panda 2 K, NS 10012) at 25 ^° C. and 400 bar for 15 minutes. A transparent solubilizate could be obtained which had micelles with an average size (diameter) of 70 nm. Subsequently, the emulsions are fed to a spray drying process based on spouted bed technology. It was possible to obtain free-flowing, readily processable powders.

Example 4:

20 g of glucose and 34 g of sodium ascorbate are dissolved in 40 g of water. Subsequently, 5 g of lecithin (85% phosphatidylcholine) and 1 g of diclofenac sodium are added while homogenizing.

The homogenate is homogenized in a high-pressure homogenizer (Panda 2 K, NS 10012) at 25 ^° C. and 400 bar for 15 minutes. A transparent solubilizate could be obtained which had micelles with an average size (diameter) of 70 nm. The composition remains stable when stored for 6 months at 25 ⁰ C unchanged. Example 5:

20 g of glucose and 34 g of sodium ascorbate are dissolved in 40 g of water. Subsequently, 5 g of lecithin (85% phosphatidylcholine) and 1 g of dexamethasone are added while homogenizing.

The homogenate is homogenized in a high-pressure homogenizer (Panda 2 K, NS 10012) at 25 ^° C. and 400 bar for 15 minutes. A transparent solubilizate could be obtained which had micelles with an average size (diameter) of 70 nm. The composition remains stable when stored for 6 months at 25 ⁰ C unchanged.

Example 6:

20 g of glucose and 32 g of sodium ascorbate are dissolved in 40 g of water. Subsequently, 5 g of lecithin (85% phosphatidylcholine) and 3 g of ibuprofen-DL-lysinate are added while homogenizing.

Example 7:

20 g of glucose and 30 g of sodium ascorbate are dissolved in 40 g of water. Subsequently, 5 g of lecithin (85% phosphatidylcholine) and 5 g of acetylsalicylic acid are added while homogenizing.

The homogenate is homogenized in a high-pressure homogenizer (Panda 2 K, NS 10012) at 25 ^° C. and 400 bar for 15 minutes. A transparent solubilizate could be obtained which had micelles with an average size (diameter) of 70 nm. The composition remains stable when stored for 6 months at 25 ⁰ C unchanged. Example 8:

20 g of glucose and 25 g of sodium ascorbate are dissolved in 40 g of water. Subsequently, 5 g of lecithin (85% phosphatidylcholine), 6 g of carnitine and 4 g of nicotinamide are added while homogenizing.

The homogeneous isat is in the high-pressure homogenizer (Panda 2K, NS 10012) at 25 ⁰ C and homogenized 400 bar for 15 minutes. A transparent solubilizate could be obtained which had micelles with an average size (diameter) of 70 nm. The composition remains stable when stored for 6 months at 25 ⁰ C unchanged.

Example 9:

20 g of glucose and 26 g of sodium ascorbate are dissolved in 40 g of water. Subsequently, 5 g of lecithin (85% phosphatidylcholine) and 9 g of lysine mono- (acetylsalicylate) are added while homogenizing.

Example 10:

20 g of glucose and 26 g of sodium ascorbate are dissolved in 40 g of water. Subsequently, 5 g of lecithin (85% phosphatidylcholine) and 10 g of grapeseed oil are added while homogenizing.

The homogenate is homogenized in a high-pressure homogenizer (Panda 2 K, NS 10012) at 25 ^° C. and 400 bar for 15 minutes. It could be obtained a solubilizate, the micelles with an average size (Diameter) of 70 nm. The composition remains stable when stored for 6 months at 25 ⁰ C unchanged.

Example 11:

20 g of glucose and 26 g of sodium ascorbate are dissolved in 40 g of water. Subsequently, 5 g of lecithin (85% phosphatidylcholine) and 3 g of testosterone are added while homogenizing.

Example 12:

The following emulsion according to the invention was prepared:

Table 4: Micellar emulsion

¹ Cx phospholipid GmbH, Germany

* Esterification products of glycerol with a mixture of caprylic acid and

capric acid

The composition set out in Table 4 is homogenized by means of a high-pressure homogenizer. It creates a transparent micellar concentrate with a mean diameter of the micelles of 70 nm.

Example 13:

5 kg of the micellar concentrate obtained in Example 12 are diluted with 10 l of water. This solution is then processed with a 15% aqueous solution of potassium and sodium 2: 1 in a spray dryer. A colorless, water-soluble powder is obtained.

Example 14:

Table 5: Micellar emulsion

¹ Cx phospholipid GmbH, Germany

After the high-pressure homogenization described above, a micellar concentrate is obtained with an average diameter of the micelles of 70 nm. Example 15:

Table 6:

After Hodruckhomogenisierung a micellar concentrate is obtained with an average diameter of 80 nm.

Table 7: Inventive drink

Water and glucose and lecithin and sodium ascorbate are stirred first to form a micellar emulsion, then the other components are added and the entire mixture is high pressure homogenized. A transparent beverage having an average micelle diameter of 70 nm is obtained.

Claims

claims:

1. Liquid aqueous, micellar emulsion containing a) one or more phospholipid (s), b) a micelle stabilizer consisting of carnitine and / or a physiologically acceptable carnitine derivative and / or polyol (s), and c) a radical scavenger selected from the group consisting of ascorbic acid and / or alkali and / or alkaline earth salts of ascorbic acid and / or esters of one or more organic acid (s) with ascorbic acid and / or physiologically acceptable derivatives of ascorbic acid, characterized in that the micelles have an average diameter of 3 up to 250 nm.

2. Liquid aqueous, micellar emulsion according to claim 1, characterized in that the micelles have an average diameter of 10 to 120 nm, preferably from 20 to 100 nm, in particular from 50 to 80 nm.

3. Liquid aqueous micellar emulsion according to claim 1 or 2, characterized in that the emulsion is transparent.

4. Liquid aqueous micellar emulsion according to one of claims 1 to 3, containing one or more phospholipid (s) in an amount of 0.4 to 50 wt .-%, more preferably from 0.7 to 40 wt .-%, particularly preferably from 2 to 20% by weight and in particular from 2.5 to 15% by weight, especially from 4 to 10% by weight and very preferably from 4 to 6% by weight, in each case based on the total emulsion ,

5. Liquid aqueous micellar emulsion according to one of claims 1 to

4, containing lecithin, in particular soya lecithin or egg lecithin.

6. Liquid aqueous, micellar emulsion according to one of claims 1 to

5, containing polyol in an amount of 3.5 to 60 wt .-%, preferably from 20 to 60 wt .-% and in particular from 25 to 45 wt .-%, each based on the total emulsion.

7. Liquid aqueous micellar emulsion according to one of claims 1 to

6, characterized in that the polyol is selected from the group consisting of glucose, chodroitin sulfate, glucosamine sulfate, glycerol, mannitol, mannitol, maltodextrin, pectin and sorbitol.

8. Liquid aqueous micellar emulsion according to one of claims 1 to

7, characterized in that the radical scavenger is present in an amount of 4 to 50 wt .-%, particularly preferably from 5 to 45 wt .-% and in particular from 7 to 30 wt .-%, each based on the total emulsion.

9. Liquid aqueous micellar emulsion according to one of claims 1 to

8, characterized in that the radical scavenger selected from the group consisting of sodium or potassium ascorbate.

10. Liquid aqueous micellar emulsion according to any one of claims 1 to

9, characterized in that the emulsion has a pH of 4.0 to 9.5.

11. Liquid aqueous, micellar emulsion according to one of claims 1 to

10, containing

4 to 6% by weight of lecithin,

From 25 to 45% by weight of glucose,

From 7 to 30% by weight of sodium and / or potassium ascorbate, 0 to 20 wt .-%, preferably 5 to 15 wt .-% carnitine, wherein the weight percentages are based on the total emulsion.

12. Liquid aqueous micellar emulsion according to one of claims 1 to

11, additionally containing taurine and / or caffeine.

13. Liquid aqueous micellar emulsion according to any one of claims 1 to

12, characterized in that it is substantially free of fructose.

14. Liquid aqueous micellar emulsion according to one of claims 1 to

13, characterized in that it additionally comprises one or more lipophilic solubilizable (s) substance (s) selected from the group of the C ₀ - C ₃₀ - fatty acids, waxes or their esters, paraffins, C ₀ -C ₃₀ - fatty alcohols, Ci _O C _{3O fatty} aldehydes, triglycerides, oils, isoprenoids, terpenes, citral, menthol camphor, bisabolol, cholesterol or its derivatives, vitamin D, testosterone, estrogen, progesterone, cortisol, aldosterone and their respective physiologically acceptable / acceptable derivatives, ethinylestradiol, sitosterols , Vitamin A, vitamin K, vitamin E, tocopherols, tocotrienols, carotenoids, beta-carotene, lutein, zeaxanthin or their physiologically tolerated derivatives, coenzyme Q10 and polar lipids, ceramides, sphingilipids, glycolipids, amines, amino acids, peptides or their derivatives, Silicone oils as well as lipophilic UV-A and UV-B filters.

15. Liquid aqueous micellar emulsion according to one of claims 1 to

14, characterized in that additionally at least one member selected from the group containing melatonin, 5-hydroxytryptophan, tryptophan, serotonin, tyrosine, dopamine or L-dopa is included.

16. A liquid aqueous micellar emulsion according to any one of claims 1 to

15, characterized in that a vitamin selected from the B series is zusäztlich included.

17. Liquid aqueous, micellar emulsion according to one of claims 1 to

16, characterized in that additionally at least one member selected from the group containing non-steroidal analgesics, non-steroidal anti-inflammatory drugs, steroidal analgesics, steroidal anti-inflammatory drugs, antihistamines, local anesthetics, alkaloids, anticoagulants, parasympathomines, Parasympatholytika, sympathomimetics or antimycotics is included.

18. Liquid aqueous, micellar emulsion according to one of claims 1 to

17, characterized in that they additionally one or more amino acids selected from the group consisting of glycine, alanine, leucine, isoleucine, valine, lysine, methionine, phenylalanine, threonine, arginine, cysteine, glutamate, serine, taurine, asparagine, glutamic ornithine and proline.

19. Liquid aqueous micellar emulsion according to any one of claims 1 to

18, characterized in that it additionally contains glutathione or creatine.

20. Liquid aqueous micellar emulsion according to one of claims 1 to

19, characterized in that it additionally contains lipoic acid and para-aminobenzoic acid.

21. Liquid aqueous, micellar emulsion according to one of claims 1 to

20, characterized in that it additionally contains minerals or trace elements.

22. Liquid aqueous micellar emulsion according to one of claims 1 to 21, characterized in that it additionally contains purines, in particular selected from the group consisting of caffeine, theophylline and theobromine.

23. A process for the preparation of a solid composition, characterized in that a liquid aqueous micellar emulsion according to any one of claims 1 to 22 is spray-dried.

24. The method according to claim 23, characterized in that the liquid aqueous micellar emulsion together with another aqueous formulation A containing a polycarboxylic acid salt, preferably citric acid salt, in particular calcium, magnesium, potassium, and / or sodium or gluconic acid, in particular Na, Mg, K or Ca gluconate, which is spray-dried.

25. Powder obtainable by a process according to one of claims 23 or 24.

26. A cosmetic or pharmaceutical or dietetic composition containing an emulsion according to any one of claims 1 to 22 or a powder according to claim 25.

27. A beverage containing a liquid, aqueous, micellar emulsion according to any one of claims 1 to 22 or a powder according to claim 25.

28. A lollipop or gum containing the aqueous micellar emulsion according to any one of claims 1 to 22 or a powder according to claim 25.

29. Use of the aqueous, micellar emulsion according to any one of claims 1 to 22 or of the powder according to claim 25 as an additive in cosmetic, pharmaceutical or dietetic formulations.