EP2034961A1 - Formulations de solubilisât - Google Patents

Formulations de solubilisât

Info

Publication number
EP2034961A1
EP2034961A1 EP07728370A EP07728370A EP2034961A1 EP 2034961 A1 EP2034961 A1 EP 2034961A1 EP 07728370 A EP07728370 A EP 07728370A EP 07728370 A EP07728370 A EP 07728370A EP 2034961 A1 EP2034961 A1 EP 2034961A1
Authority
EP
European Patent Office
Prior art keywords
emulsion according
liquid aqueous
micellar emulsion
micellar
group
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP07728370A
Other languages
German (de)
English (en)
Inventor
Gertrud Langhoff
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from EP06116454A external-priority patent/EP1875896A1/fr
Application filed by Individual filed Critical Individual
Priority to EP07728370A priority Critical patent/EP2034961A1/fr
Publication of EP2034961A1 publication Critical patent/EP2034961A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches

Definitions

  • 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.
  • phospholipid s
  • a micelle stabilizer consisting of carnitine and / or a physiologically tolerated carnitine derivative and / or polyols
  • 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 ascor
  • 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.
  • 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.
  • the long-term degradation of fatty acids in phosphatidylcholine by free-radical processes is taken into account in the formulation.
  • the formulations disclosed in DE 102 55 195 Al lead the body to large amounts of sugar.
  • 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.
  • 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.
  • 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.
  • the compositions of the invention preferably contain phospholipids which are derivatives of glycerol and are also referred to as phosphoglycerides or phosphatides.
  • 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.
  • 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.
  • PAF platelet-activating factor
  • 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.
  • 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.
  • AIIg Structure of lecithins; R1, R2: typically unbranched aliphatic radicals having 15 or 17 carbon atoms and up to 4 cis double bonds.
  • ⁇ -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.
  • a soybean lecithin fraction contains palmitic acid, stearic acid, palmitoleic acid, oleic acid, linoleic acid and linolenic acid.
  • the saturated fatty acid is esterified with the primary, the unsaturated with the secondary hydroxy group of glycerol.
  • the emulsions according to the invention comprise phospholipid which has been obtained from soybean and / or oilseed rape and / or egg.
  • the emulsions according to the invention contain hydrogenated and / or hydrolyzed and / or hydroxylated phospholipids.
  • 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.
  • compositions according to the invention are 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.
  • radical scavengers selected from the group consisting of sodium ascorbate or potassium ascorbate are particularly preferred.
  • the compositions according to the invention comprise esters, preferably monoesters, of organic acids with ascorbic acid.
  • the radical scavenger is a C 8 -C 30 - fatty acid ester, preferably C 8 -C 3 o-Fettklaremonoester, more preferably Ci 2 -C 22 -Fettklaremonoester, 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 ,
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the emulsions of the invention below 5 wt .-%, preferably below 2.5 wt .-%, more preferably below 1 wt .-% Ci-CrMonoalkohole on.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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 ,
  • the emulsions may additionally contain glutathione or creatine as well as a combination of lipoic acid and para-aminobenzoic acid.
  • 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.
  • 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
  • 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,
  • the solubilisable substance is preferably selected from the group of steroidal analgesics and / or antirheumatics.
  • 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.
  • (partial) synthetic analgesics are preferred.
  • 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.
  • the solubilizable substance is selected from the group of antihistamines.
  • 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 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
  • Clemastin hydrogen fumarate and citrizine such as citrizine hydrochloride proved.
  • the solubilisable substance is preferably selected from the group of local anesthetics.
  • 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 as lidocaine hydrochloride and / or procaine and their physiologically acceptable derivatives such as e.g. Procaine hydrochloride proved.
  • the solubilizable substance is selected from the group of alkaloids.
  • Ephedrine and their physiologically acceptable derivatives such as ephedrine hydrochloride and / or pseudoephedrine and their physiologically acceptable derivatives such as pseudoephedrine hydrochloride proved.
  • 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.
  • the solubilisable substance is preferably selected from the group of antimycotics.
  • 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, Tiocona
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the homogenization by means of a high pressure homogenizer has been found to be particularly suitable.
  • 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.
  • 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.
  • the spray-drying process for recovering the solid has proven particularly suitable.
  • 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.
  • Spray drying is a continuous process for drying solutions, suspensions or pasty materials.
  • a nozzle operated by liquid pressure or compressed air or inert gas
  • rotating atomizing disks 400-50000 rpm
  • 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.
  • 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).
  • process gas dry gas
  • the air does not enter the process chamber from below through a sieve bottom, but rather through longitudinal gaps in the lower area.
  • 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.
  • 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.
  • the method according to the invention are located above thekowskizaseinströmspalts plates, which are preferably arranged regularly on both sides of the gap, so that the width of thetergaseinströmspaltes 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.
  • 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.
  • 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.
  • the aforementioned plates are chamfered at their ends to theregaseinströmspalt 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.
  • 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.
  • the aqueous liquid emulsion according to the invention 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.
  • the feed of the aqueous formulation A is carried out separately from the liquid emulsion according to the invention to be dried.
  • 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.
  • 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.
  • Another object of the present invention is a solid, preferably a powder, which is obtainable from the process according to the invention.
  • 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
  • a cosmetic or pharmaceutical or dietetic composition comprising a solid according to the invention or a liquid emulsion according to the invention.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the emulsions are fed to a spray drying process based on spouted bed technology. It was possible to obtain free-flowing, readily processable powders.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • micellar concentrate obtained in Example 12 5 kg 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.
  • micellar concentrate is obtained with an average diameter of the micelles of 70 nm.
  • micellar concentrate is obtained with an average diameter of 80 nm.
  • micellar emulsion 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.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nutrition Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Mycology (AREA)
  • Dispersion Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des émulsions micellaires aqueuses liquides comprenant un ou plusieurs phospholipide(s), un stabilisateur micellaire, composé de carnitine et/ou d'un dérivé de carnitine physiologiquement acceptable et/ou de polyols, ainsi qu'un capteur de radicaux, choisi dans le groupe comprenant l'acide ascorbique et/ou les sels alcalins et/ou alcalino-terreux de l'acide ascorbique et/ou l'ester d'un ou de plusieurs acide(s) organique(s) avec l'acide ascorbique et/ou des dérivés physiologiquement acceptables de l'acide ascorbique. La présente invention concerne également un procédé de fabrication de compositions solides et de formulations cosmétiques ou pharmaceutiques ou diététiques, qui contiennent une émulsion ou une poudre fabriquée à partir de celle-ci ou utilisent cette composition comme additif. La présente invention concerne en outre des boissons, bonbons à sucer et gommes de base, qui contiennent l'émulsion ou une poudre fabriquée à partir de celle-ci.
EP07728370A 2006-06-30 2007-04-20 Formulations de solubilisât Withdrawn EP2034961A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP07728370A EP2034961A1 (fr) 2006-06-30 2007-04-20 Formulations de solubilisât

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP06116454A EP1875896A1 (fr) 2006-06-30 2006-06-30 Formulation solubilisé
EP06024724 2006-11-29
PCT/EP2007/053913 WO2008000534A1 (fr) 2006-06-30 2007-04-20 Formulations de solubilisât
EP07728370A EP2034961A1 (fr) 2006-06-30 2007-04-20 Formulations de solubilisât

Publications (1)

Publication Number Publication Date
EP2034961A1 true EP2034961A1 (fr) 2009-03-18

Family

ID=38293249

Family Applications (1)

Application Number Title Priority Date Filing Date
EP07728370A Withdrawn EP2034961A1 (fr) 2006-06-30 2007-04-20 Formulations de solubilisât

Country Status (2)

Country Link
EP (1) EP2034961A1 (fr)
WO (1) WO2008000534A1 (fr)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8497258B2 (en) 2005-11-12 2013-07-30 The Regents Of The University Of California Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract
DE202008008059U1 (de) * 2008-06-18 2009-10-29 Langhoff, Gertrud Zusammensetzung zur Prophylaxe und Therapie der Arthrose
EP2179739A1 (fr) * 2008-10-23 2010-04-28 Matteo Tutino Compositions comportant des vitamines
DE102010033458B4 (de) 2010-08-05 2016-03-10 Helvista Ag Emulgierte Lektinzusammensetzungen und ihre Verwendung
DE102011105703A1 (de) 2011-06-22 2012-12-27 Wolfgang Langhoff Diätetikum zur Behandlung mitochondrialer Dysfunktionen
WO2016119143A1 (fr) * 2015-01-28 2016-08-04 晨光生物科技集团股份有限公司 Préparation de microcapsules de lutéine et méthode de préparation
WO2017120592A1 (fr) * 2016-01-08 2017-07-13 Western University Of Health Sciences Formulations d'undécanoate de testostérone proliposomales
CN114788791A (zh) 2017-06-23 2022-07-26 宝洁公司 用于改善皮肤外观的组合物和方法
WO2019233552A1 (fr) * 2018-06-05 2019-12-12 Pm-International Ag Système à deux phases
CN112437657A (zh) 2018-07-03 2021-03-02 宝洁公司 处理皮肤状况的方法
US10959933B1 (en) 2020-06-01 2021-03-30 The Procter & Gamble Company Low pH skin care composition and methods of using the same
EP4157206A1 (fr) 2020-06-01 2023-04-05 The Procter & Gamble Company Méthode d'amélioration de la pénétration d'un composé de vitamine b3 dans la peau
US11992483B2 (en) 2021-03-31 2024-05-28 Cali Biosciences Us, Llc Emulsions for local anesthetics
CN116869971B (zh) * 2023-08-02 2024-04-05 广东润和生物科技有限公司 一种辅酶q10缓释软胶囊以及制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1099584A (zh) * 1993-08-28 1995-03-08 北京赋仁德保健新技术开发公司 含天然大豆磷脂脂质体饮品及其制法
EP0659347A1 (fr) * 1993-12-20 1995-06-28 San-Ei Gen F.F.I., Inc. Compositions émulsifiées stables et aliments les contenant
DE29704822U1 (de) * 1997-03-17 1997-05-15 Lucas Meyer GmbH & Co, 20539 Hamburg Proliposomale Zusammensetzungen zur Herstellung von Getränken

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1190370B (it) * 1985-06-19 1988-02-16 Zambon Spa Composizione farmaceutica solida per uso orale
WO1988006441A1 (fr) * 1987-02-23 1988-09-07 Vestar, Inc. Deshydratation de preparations vesiculaires pour stockage a longterme
ES2152324T3 (es) * 1993-07-28 2001-02-01 Pharmaderm Lab Ltd Vesiculas lipidicas multilaminares bifasicas.
DE4432378A1 (de) * 1994-09-12 1996-03-14 Bayer Ag Injizierbare liposomale Arzneizubereitungen
DE10036797A1 (de) * 2000-07-28 2002-02-07 Beiersdorf Ag Verwendung von Kombinationen mit einem Gehalt an Carnitinen
DE10255195A1 (de) * 2002-11-27 2004-06-09 Lipoid Gmbh Micellare wasserlösliche Konzentrate

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1099584A (zh) * 1993-08-28 1995-03-08 北京赋仁德保健新技术开发公司 含天然大豆磷脂脂质体饮品及其制法
EP0659347A1 (fr) * 1993-12-20 1995-06-28 San-Ei Gen F.F.I., Inc. Compositions émulsifiées stables et aliments les contenant
DE29704822U1 (de) * 1997-03-17 1997-05-15 Lucas Meyer GmbH & Co, 20539 Hamburg Proliposomale Zusammensetzungen zur Herstellung von Getränken

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DATABASE GNPD [online] 1 February 2005 (2005-02-01), "Nan 1 Starter Infant Formula Powder with Iron", Database accession no. 341991 *
See also references of WO2008000534A1 *
VOIGT: "Pharmazeutische Technologie: für Studium und Beruf", 1 January 2006, DEUTSCHER APOTHEKER VERLAG, pages: 554 - 555 *

Also Published As

Publication number Publication date
WO2008000534A1 (fr) 2008-01-03

Similar Documents

Publication Publication Date Title
EP2034961A1 (fr) Formulations de solubilisât
DE60132081T2 (de) ZUBEREITUNG ZUR VORBEUGUNG UND BEHANDLUNG VON GEFÄßKRANKHEITEN
JP6211603B2 (ja) クルクミンを含有する改善された複合体および組成物
EP2986141B1 (fr) Encapsulation d'une huile contenant des acides gras insaturés
DE60219174T2 (de) Mikronährstoff-phosphate als nahrungsergänzungsmittel und mittel zur förderung der gesundheit
PL197342B1 (pl) Zastosowanie L-karnityny lub alkanoilo-L-karnityny oraz trihydroksystylbenu lub tetrahydroksystylbenu
JP2015518862A5 (fr)
WO2009093650A1 (fr) Emulsion grasse contenant des prostaglandines et procédé de production associé
US9056056B2 (en) Processing for dispersing amino acids
EP0242812B1 (fr) Utilisation du glycofurol pour liquéfier des préparations pharmaceutiques pour le remplissage de capsules de gélatine
WO2009153200A1 (fr) Préparation contenant de la glucosamine et/ou de la chondroïtine pour la prophylaxie et la thérapie de l'arthrose et pour le renforcement du système immunitaire
WO2012150890A1 (fr) Composition antibactérienne
EP1499204A2 (fr) Matrice dure et stable contenant des phospholipides et physiologiquement compatibles
EP3099289B1 (fr) Composition comprenant des triglycérides epa et dha pour administration parentérale
EP1875896A1 (fr) Formulation solubilisé
EP1745788A1 (fr) Acylglycerophospholipides pour le traitement du cancer et de la cachexie
DE102011105703A1 (de) Diätetikum zur Behandlung mitochondrialer Dysfunktionen
EP1659878B1 (fr) Formulation a base de phospholipides
DE102014007762A1 (de) Kohlehydrat-Konzentrat, Verfahren zu seiner Herstellung und wässriges Getränkekonzentrat
DE102009012465A1 (de) Pharmazeutische Zusammensetzung zur Prophylaxe und Behandlung der Arteriosklerose, sowie zur Schmerzbekämpfung und zur Entzündungshemmung
WO2021209541A1 (fr) Formulation de taxifoline comprenant de la thiamine
DE202013002498U1 (de) Futtermittelzusatz für Nutz- und Haustiere
KR20120062208A (ko) 홍삼 오일을 부형제 오일로 함유하는 연질캡슐제
EP3042648B1 (fr) Granules directs a agent actif retarde
JP5114397B2 (ja) ヒアルロン酸リン脂質複合体及びその調製法

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20090119

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC MT NL PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA HR MK RS

17Q First examination report despatched

Effective date: 20090409

DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20120828