EP1901619A1 - Suspensions aqueuses de substances actives difficilement solubles dans l'eau ou insolubles dans l'eau et poudres seches produites a partir des dites suspensions - Google Patents

Suspensions aqueuses de substances actives difficilement solubles dans l'eau ou insolubles dans l'eau et poudres seches produites a partir des dites suspensions

Info

Publication number
EP1901619A1
EP1901619A1 EP06763992A EP06763992A EP1901619A1 EP 1901619 A1 EP1901619 A1 EP 1901619A1 EP 06763992 A EP06763992 A EP 06763992A EP 06763992 A EP06763992 A EP 06763992A EP 1901619 A1 EP1901619 A1 EP 1901619A1
Authority
EP
European Patent Office
Prior art keywords
water
soluble
insoluble active
aqueous suspensions
whey protein
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Withdrawn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
EP06763992A
Other languages
German (de)
English (en)
Inventor
Jesper Feldthusen Jensen
Christian KÖPSEL
Heike Schuchmann
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.)
BASF SE
Original Assignee
BASF SE
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
Application filed by BASF SE filed Critical BASF SE
Publication of EP1901619A1 publication Critical patent/EP1901619A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K50/00Feeding-stuffs specially adapted for particular animals
    • A23K50/80Feeding-stuffs specially adapted for particular animals for aquatic animals, e.g. fish, crustaceans or molluscs
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/142Amino acids; Derivatives thereof
    • A23K20/147Polymeric derivatives, e.g. peptides or proteins
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/158Fatty acids; Fats; Products containing oils or fats
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/179Colouring agents, e.g. pigmenting or dyeing agents
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K40/00Shaping or working-up of animal feeding-stuffs
    • A23K40/10Shaping or working-up of animal feeding-stuffs by agglomeration; by granulation, e.g. making powders
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, 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
    • A23L29/00Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/10Foods or foodstuffs containing additives; Preparation or treatment thereof containing emulsifiers
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, 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
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, 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
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15Vitamins
    • A23L33/155Vitamins A or D
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, 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
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17Amino acids, peptides or proteins
    • A23L33/18Peptides; Protein hydrolysates
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, 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
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17Amino acids, peptides or proteins
    • A23L33/19Dairy proteins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60Sugars; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/981Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
    • A61K8/986Milk; Derivatives thereof, e.g. butter
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q1/00Make-up preparations; Body powders; Preparations for removing make-up
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B82NANOTECHNOLOGY
    • B82YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00Function of food ingredients
    • A23V2200/20Ingredients acting on or related to the structure
    • A23V2200/25Nanoparticles, nanostructures
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41Particular ingredients further characterized by their size
    • A61K2800/413Nanosized, i.e. having sizes below 100 nm

Definitions

  • the present invention relates to aqueous suspensions containing
  • sucrose fatty acid ester having an HLB value in the range of 10 to 18.
  • the preparation of finely divided, powdered carotenoid preparations is carried out by, for example, ⁇ -carotene in a volatile, water-miscible organic solvent at temperatures between 50 0 C and 200 0 C, optionally under elevated pressure, within a time of less than 10 seconds. From the resulting molecularly dispersed solution, the ⁇ -carotene is precipitated by immediate rapid mixing with an aqueous solution of a protective colloid at temperatures between 0 0 C and 50 0 C.
  • WO 98/26008 relates to the use of a mixture of low molecular weight and high molecular weight protective colloids for the preparation of redispersible xanthophyll-containing dry powders.
  • stable means that the formulations have a duration and temperature range which is adequate for the respective application. oxidation and photostable and sedimentation and Aufrahmstabil are.
  • the object according to the invention was achieved by aqueous suspensions containing
  • sucrose fatty acid ester having an HLB value in the range of 10 to 18.
  • aqueous suspensions in which the dispersed phase contains at least one sparingly water-soluble or water-insoluble active substance as nanoparticulate particles.
  • the dry powders or emulsions prepared from the above aqueous suspensions preferably double emulsions, in particular O / W / O emulsions.
  • the term "sparingly water-soluble organic active ingredients” refers to those compounds whose water solubility is ⁇ 5% by weight, preferably ⁇ 1% by weight, more preferably ⁇ 0.1% by weight, very particularly preferably ⁇ 0.01% by weight .-% is.
  • Fat soluble vitamins e.g. K vitamins, vitamin A and derivatives such as vitamin A acetate, vitamin A propionate or vitamin A palmitate, vitamin D2 and vitamin D3, and vitamin E and derivatives.
  • vitamin E is natural or synthetic ⁇ -, ⁇ -, ⁇ - or ⁇ -tocopherol, preferably natural or synthetic ⁇ -tocopherol and tocotrienol.
  • Vitamin E derivatives are e.g. Tocopheryl Ci-C2o carboxylic acid esters such as tocopheryl acetate or tocopheryl palmitate.
  • Polyunsaturated fatty acids e.g. Linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid.
  • Food colors such as curcumin, carmine or chlorophyll.
  • Carotenoids both carotenes, e.g. ⁇ -carotene and lycopene as well as xanthophylls, e.g. Lutein, astaxanthin, zeaxanthin, capsanthin, capsorubin, cryptoxanthin, citranaxanthin, canthaxanthin, bixin, ⁇ -apo-4-carotenal, ⁇ -apo-8-carotenal and ⁇ -apo-8-carotenoic acid ethyl ester.
  • xanthophylls e.g. Lutein, astaxanthin, zeaxanthin, capsanthin, capsorubin, cryptoxanthin, citranaxanthin, canthaxanthin, bixin, ⁇ -apo-4-carotenal, ⁇ -apo-8-carotenal and ⁇ -apo-8-carotenoic acid ethyl ester.
  • Water-insoluble or sparingly water-soluble organic UV filter substances such as, for example, compounds from the group of the triazines, anilides, benzophenones, triazoles, cinnamamides and the sulfonated benzimidazoles.
  • Preferred active ingredients are carotenes, especially .beta.-carotene, lycopene and xanthophylls, in particular, lutein, astaxanthin and canthaxanthin as well as vitamin A and vitamin E and from the series of UV filter substances the substance class of the triazines, in particular Uvinul T150.
  • a particularly preferred embodiment of the aqueous suspensions according to the invention is characterized in that they are aqueous suspensions which contain at least one sparingly water-soluble or water-insoluble active ingredient selected from the group of carotenoids consisting of ⁇ -carotene, lycopene, lutein, astaxanthin and canthaxanthin , very particularly preferably lycopene or astaxanthin as nanoparticulate particles.
  • whey proteins in combination with sucrose laurate are preferred, whereas whey protein hydrolysates in combination with sucrose laurate are preferably used for aqueous suspensions of xanthophylls.
  • the solids content in the aqueous suspensions according to the invention is in the range from 0.1 to 70% by weight, preferably 0.5 to 50% by weight, particularly preferably in the range from 10 to 40% by weight.
  • the average particle size of the active ingredient particles in the aqueous suspension is in the range from 0.01 to 100 ⁇ m, preferably in the range from 0.01 to 10 ⁇ m, particularly preferably in the range from 0.01 to 2 ⁇ m preferably in the range of 0.02 to 1 micron.
  • the aqueous suspension according to the invention contains a whey protein (bi) and / or a whey protein hydrolyzate (b2).
  • the whey protein used is preferably a spray-dried whey protein isolate having a protein content of at least 80%, more preferably having a protein content of at least 95%.
  • whey protein hydrolyzate (b2) preference is given to using purified, enzymatically degraded whey proteins having a degree of hydrolysis of from 3 to 20, particularly preferably having a degree of hydrolysis of from 4 to 16 (determined by the OPA method).
  • Sucrose fatty acid esters c) having an HLB in the range of 10 to 18 include sucrose stearate, sucrose palmitate, sucrose myristate, sucrose laurate and sucrose oleate.
  • the proportion of monoester - for example, sucrose monostearate is greater than 55%, preferably in the range of 70 to 85%.
  • the preferred sucrose fatty acid ester is sucrose laurate with a sucrose monolaurate content of 75 to 85% and an HLB value of 16.
  • the amounts of the various components of the suspensions according to the invention are chosen so that the preparations are 0.1 to 90 wt .-%, preferably 1 to 50 wt .-%, particularly preferably 3 to 30 wt .-%, most preferably 5 to 25 %
  • By weight of at least one sparingly water-soluble or water-insoluble active ingredient 0.1 to 50% by weight, preferably 0.1 to 20% by weight, particularly preferably 1 to 10% by weight of a whey protein and / or a Whey protein hydrolyzate and 0.1 to 20 wt .-%, preferably 0.1 to 10 wt .-%, particularly preferably 1 to 5 wt .-% of a sucrose fatty acid ester having an HLB value in the range of 10 to 18 included ,
  • the percentages by weight in each case relate to the dry mass of the suspension.
  • Preferred aqueous suspensions in the sense of the present invention comprise a) from 0.1 to 90% by weight, preferably from 1 to 50% by weight, particularly preferably from 3 to 30% by weight, very particularly preferably from 5 to 25% by weight at least one xanthophyll, b) 0.1 to 50% by weight, preferably 0.1 to 20% by weight, particularly preferably 1 to 10% by weight of a whey protein and c) 0.1 to 20% by weight , preferably 0.1 to 10 wt .-%, particularly preferably 1 to 5 wt .-% of a sucrose laurate having an HLB value of 16, wherein all percentages are based on the dry matter of the aqueous suspensions.
  • aqueous suspensions are characterized in that they contain a) from 0.1 to 90% by weight, preferably from 1 to 50% by weight, particularly preferably from 3 to 30% by weight, very particularly preferably from 5 to 25% by weight. % of at least one carotene, b) 0.1 to 50 wt .-%, preferably 0.1 to 20 wt .-%, particularly preferably 1 to 10 wt .-% of a whey protein hydrolyzate and c) 0.1 to 20 wt .-%, preferably 0.1 to
  • the suspensions according to the invention may additionally comprise one or more protective colloids as component d).
  • suitable additional colloids are advantageously water-soluble or water-swellable protective colloids such as, for example, bovine, porcine or fish gelatin, in particular acidic or basic degraded gelatin with bloom numbers in the range of 0 to 250, most preferably gelatin A 100, A 200, B 100 and B 200 and low molecular weight, enzymatically degraded gelatin types with the Bloom number 0 and molecular weights of 15000 to 25000 D such as Collagel A and Gelitasol P ( Stoess, Eberbach) and mixtures of these types of gelatin and starch, dextrin, pectin, gum arabic, lignin sulfonates, chitosan, polystyrene sulfonate, alginates, casein, caseinate such as sodium caseinate, methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, modified starch such as sodium octenylsuccinate starch (Capsul, National Starch Co.), plant
  • Preferred protective colloids are modified starch, casein and / or sodium caseinate, soy protein and gelatin, particularly preferred are casein and / or sodium caseinate
  • the amount of additionally used protective colloid is from 0.1 to 50 wt .-%, preferably 1 to 30 wt .-%, particularly preferably 2 to 20 wt .-%, most preferably from 3 to 10 wt .-%, based on the dry matter of the formulation.
  • the suspensions may also contain low molecular weight stabilizers such as antioxidants and / or preservatives to protect the active ingredients.
  • Suitable antioxidants or preservatives are, for example, ⁇ -tocopherol, ascorbic acid, tert-butyl-hydroxytoluene, tert-butylhydroxyanisole, lecithin, ethoxyquin, methylparaben, propylparaben, sorbic acid or sodium benzoate.
  • the antioxidants or preservatives may be used in amounts of 0.01 to 50 wt .-%, preferably 0.1 to 30 wt .-%, particularly preferably 0.5 to 20 wt .-%, most preferably 1 to 10 wt. -%, based on the dry weight of the formulation used.
  • the suspensions may also contain plasticizers for increasing the mechanical stability of a dry powder which may be produced therefrom.
  • plasticizers are, for example, sugars and sugar alcohols such as sucrose, maltose, glucose, lactose, trehalose, invert sugar, sorbitol, mannitol, XyNt, glucose syrup, maltodextrin or glycerol. Maltodextrin and / or glucose syrup are preferably used as plasticizers.
  • the plasticizers may be present in amounts of from 0.1 to 70% by weight, preferably from 10 to 60% by weight, particularly preferably from 20 to 50% by weight, based on the dry weight of the formulation.
  • the suspensions may contain additional low molecular weight surface-active compounds (emulsifiers) in a concentration of from 0.01 to 70% by weight, preferably from 0.1 to 50% by weight, more preferably from 0.5 to 20 Wt .-%, based on the dry matter of the formulation.
  • emulsifiers emulsifiers
  • amphiphilic compounds or mixtures of such compounds emulsifiers
  • suitable surface-active substances are esters of long-chain fatty acids with ascorbic acid, mono- and diglycerides of fatty acids and their oxyethylation products, esters of monofatty acid glycerides with acetic acid, citric acid, lactic acid or diacetyltartaric acid, polyglycerol fatty acid esters such as the monostearate of triglycerol, sorbitan fatty acid esters, propylene glycol fatty acid esters and lecithin. Ascorbyl palmitate is preferably used.
  • the invention also provides a process for preparing aqueous suspensions of at least one sparingly water-soluble or water-insoluble active ingredient by suspending one or more sparingly water-soluble or water-insoluble active ingredients a) in an aqueous molecular-disperse or colloidal-disperse solution containing bi) a whey protein and / or b 2 ) Whey protein hydrolyzate; and c) a sucrose fatty acid ester having an HLB value in the range of 10 to 18.
  • the water-miscible solvents used in step ai) are, above all, water-miscible, thermally stable, volatile solvents which contain only carbon, hydrogen and oxygen, such as alcohols, ethers, esters, ketones and acetals. It is expedient to use those solvents which are at least 10% water-miscible are, have a boiling point below 200 0 C and / or have less than 10 carbons. Particular preference is given to using methanol, ethanol, n-propanol, isopropanol, 1-methoxy-1,2-butanediol, 1-n-propoxy-1,2-propanediol, tetrahydrofuran or acetone.
  • a water-immiscible organic solvent in the context of the present invention for an organic solvent having a water solubility at atmospheric pressure of less than 10%.
  • solvents come u.a. halogenated aliphatic hydrocarbons, e.g. Methylene chloride, chloroform and carbon tetrachloride, carboxylic esters such as dimethyl carbonate,
  • Preferred water-immiscible organic solvents are the following compounds selected from the group consisting of dimethyl carbonate, propylene carbonate, ethyl formate, ethyl acetate, isopropyl acetate and methyl tert. butyl ether.
  • a particularly preferred solvent for the dispersing / suspending step is used at least one water-miscible organic solvent or a mixture of water and at least one water-miscible organic solvent, most preferably isopropanol or acetone.
  • step a) the molecular disperse solution of at least one sparingly water-soluble or water-insoluble active ingredient at temperatures greater than 30 0 C, preferably between 50 0 C and 240 0 C, in particular 100 0 C to 200 0 C, more preferably 140 0 C to 180 0 C, optionally under pressure, produces and immediately afterwards in step b) with the aqueous solution of the protective colloid, wherein a mixing temperature of 35 ° C to 120 0 C is established.
  • the solvent component is converted into the aqueous phase and the hydrophobic phase of the active substance (s) is formed as a nanodisperse phase.
  • the invention also provides a process for producing a dry powder containing at least one sparingly water-soluble or water-insoluble one Active substance as nanoparticulate particles, characterized in that the above-described aqueous suspensions are freed from water and dried.
  • the transfer into a dry powder can u.a. by spray drying, spray cooling, freeze drying or drying in a fluidized bed, if appropriate also in the presence of a coating material.
  • Suitable coating agents are u.a. Corn starch or silica.
  • a preferred embodiment of the o.g. Process is characterized in that the prepared suspension of at least one sparingly water-soluble or water-insoluble active ingredient is ground before being converted into a dry powder.
  • the grinding can be carried out in a manner known per se, e.g. done with a ball mill. Depending on the type of mill used, the particles are ground until the particles have a mean particle size D [4,3] of 0.1 to. Calculated by Fraunhofer diffraction
  • microns 100 microns, preferably 0.2 to 50 microns, more preferably 0.2 to 20 microns, most preferably 0.2 to 5 .mu.m, in particular 0.2 to 0.8 microns.
  • D [4,3] denotes the volume-weighted mean diameter (see Malvern Mastersizer S manual, Malvern Instruments Ltd., UK).
  • aqueous molecular disperse or colloidally disperse solution containing bi) a whey protein and / or b2) a whey protein hydrolyzate and c) a sucrose fatty acid ester having an HLB value in the range from 10 to 18 and
  • the suspension additionally contains casein and / or caseinate in process step b) as component d).
  • the invention also provides powdered preparations of at least one sparingly water-soluble or water-insoluble active ingredient obtainable by one of the abovementioned processes.
  • the invention likewise provides a process for the preparation of an oil-miscible preparation in the form of a double dispersion containing at least one sparingly water-soluble or water-insoluble active ingredient, which comprises emulsifying the aqueous suspensions described above in oil.
  • an emulsifier is used to form a water-in-oil emulsion in which the water phase contains protective colloid-stabilized nanoparticles of at least one sparingly water-soluble or water-insoluble organic UV filter substance.
  • the W / O emulsifiers known per se with an HLB value of less than 10, in particular from 2 to 6 are suitable (compare HP Fiedler, Lexikon der Hilfsstoffe für Pharmazie, Kosmetik und aboundende Zonen, 1996 , Pages 753 ff).
  • Typical representatives of this emulsifier class are partial fatty acid esters of polyhydric alcohols, e.g.
  • the dispersant may be of synthetic, mineral, vegetable or animal origin. Typical representatives are u.a. Sesame oil, sunflower oil, corn oil, cottonseed oil, soybean oil or peanut oil, esters of medium-chain vegetable fatty acids and paraffin oil, glyceryl stearate, isopropyl myristate, diisopropyl adipate, cetylstearyl 2-ethylhexanoate, hydrogenated polyisobutene, vaseline, caprylic / capric triglycerides, microcrystalline wax, lanolin and stearic acid.
  • the amount of the dispersing agent is generally 30 to 95, preferably 50 to 80 wt .-%, based on the total mass of the final emulsion.
  • the emulsification can be carried out continuously or batchwise.
  • the physical stability of the double dispersion system is achieved by a very good fine distribution of the water phase in the oil phase, for example by intensive treatment with a rotor / stator disperser at Temperatures of 20 to 80 0 C, preferably 40 to 70 0 C or with a high-pressure homogenizer such as an APV Gaulin or with a high-pressure homogenizer such as the Microfluidizer in the pressure range of 700 to 1000 bar.
  • the mean diameters of the aqueous-disperse phase which can be achieved thereby are less than 500 ⁇ m, preferably less than 100 ⁇ m, more preferably less than 10 ⁇ m, in particular less than 1 ⁇ m.
  • the invention also provides liquid, oil-miscible preparations of at least one sparingly water-soluble or water-insoluble active ingredient, obtainable by the above-mentioned process, characterized in that it comprises, as double dispersion systems, an aqueous-disperse phase having a particle diameter smaller
  • the invention also relates to the use of the o.g. aqueous suspensions as an additive to foods, food supplements, animal feeds, pharmaceutical and cosmetic preparations.
  • the invention also relates to the use of the o.g. powdered preparations as an additive to foods, food supplements, animal feeds, pharmaceutical and cosmetic preparations.
  • the invention also relates to the use of the o.g. liquid, oil-miscible preparations as an additive to foods, food supplements, animal feeds, pharmaceutical and cosmetic preparations.
  • a heatable receiver were at a temperature of 30 0 C 24.00 g of crystalline astaxanthin and ⁇ -tocopherol 9.60 g in 175 g water mixture nol suspended / an azeotropic isopropanol precipitation.
  • the active ingredient suspension was then heated to 90 0 C and at a flow rate of 2.1 kg / h with further isopropanol / water azeotrope temperature of 223 ° C and a flow rate of 2.73 kg / h batched, wherein astaxanthin dissolved at a mixing temperature of 165 ° C at a pressure of 55 bar.
  • This drug solution became immediate then, comprising (based on 5% dry matter) with an aqueous phase from a solution of 10.00 g BiPRO ®, 10.00 g sucrose laurate (5% based on dry matter), 138.24 g Glucidex ® 47 (Fa. Roquette Freres ) and 3.16 g of preservative (mixture) in 5905 g of distilled water in which the pH was adjusted to pH 9.5 with 1 M NaOH at a flow rate of 61.05 kg / h.
  • the particles of active substance formed in the mixture had a particle size of 94 nm in the isopropanol / water mixture, with an E1 / 1 value 1 'of 126.
  • the active ingredient suspension was concentrated on the thin-film evaporator to a concentration of about 23.3% by weight of dry content and spray-dried.
  • the dry powder had an astaxanthin content of 11.6% by weight.
  • the water-redispersed dry powder had a particle size of 281 nm and had an E 1/1 value of 68.
  • the E1 / 1 value defines in this context the specific extinction of a 1.0% aqueous dispersion of a 10% by weight dry powder in a 1 cm cuvette at the absorption maximum.
  • This active substance solution was immediately mixed with an aqueous phase consisting of a solution of 30.0 g BiPRO ® (10% based on dry mass), 15.0 g of L-1695 (5% based on dry matter), 192.36 g Glucidex ® 47 and 4.74 g of preservative (mixture) in 8858.42 g of distilled water in which the pH was adjusted to pH 9.5 with 1 M NaOH at a flow rate of 61, 0.05 kg / h.
  • the particles of active substance formed in the mixture had a particle size of 94 nm in the isopropanol / water mixture, with an E1 / 1 value of 126. Subsequently, the active substance suspension was concentrated on the thin-film evaporator to a concentration of about 22% solids content and spray-dried.
  • the dry powder had an astaxanthin content of 11.0% by weight.
  • the water-redispersed dry powder had a particle size of 242 nm and had an E 1/1 value of 87.
  • Astaxanthin production of a dry powder using an emulsifier combination of whey protein, sucrose laurate, and an additional protective colloid sodium caseinate, Emulac ® NA, Fa. Meggle
  • a heatable receiver were at a temperature of 30 0 C 36.00 g of crystalline astaxanthin and ⁇ -tocopherol 14.40 g in 262.64 g of an azeotropic isopropanol / water mixture suspended.
  • the active ingredient suspension was then heated to 90 0 C and at a flow rate of 2.10 kg / h with further isopropanol / water azeotrope temperature of 223 ° C and a flow rate of 2.73 kg / h mixed, the astaxanthin dissolved at a mixing temperature of 165 ° C at a pressure of 55 bar.
  • This active substance solution was immediately followed with an aqueous phase consisting of a solution of 15.00 g BiPRO ® (5% based on dry weight), 15.00 g of L-1695 (5% based on dry weight), 15.00 g of Na caseinate (5% based on dry matter), 192.36 g Gluci- dex ® 47, and 4.74 g preservatives (mixture) in 8858.42 g of distilled water in which the pH with 1M NaOH to pH 9 , 5 was mixed at a flow rate of 61, 05 kg / h.
  • the particles of active substance formed in the mixture had a particle size of 99 nm in the isopropanol / water mixture, with an E1 / 1 value of 133.
  • the active substance suspension was concentrated on the thin-film evaporator to a concentration of about 37% solids content and spray-dried.
  • the dry powder had an astaxanthin content of 11.5% by weight.
  • the water-redispersed dry powder had a particle size of 196 nm and had an E 1/1 value of 112.
  • Emulac ® NA 43.48 g (with 8% water)
  • the particles of active substance formed during milling had a particle size and E1 / 1 value of water in the water after different grinding times:
  • the dry powder (after spray-drying) had an astaxanthin content of 14.38% by weight.
  • the water-redispersed dry powder had a particle size of 207 nm and had an E 1/1 value of 111.
  • This drug solution was immediately followed by an aqueous phase consisting of a solution of 67.68 g of partially degraded soya protein (20.2% by dry matter), 187.18 g of lactose, and 16.20 g of preservative. medium (mixture) in 10818.69 g of distilled water in which the pH was adjusted to pH 9.5 with 1 M NaOH at a flow rate of 60.00 kg / h.
  • the particles of active substance formed in the mixture had a particle size of 150 nm in the isopropanol / water mixture, with an E1 / 1 value of 126.
  • the active ingredient suspension was concentrated on the thin-film evaporator to a concentration of about 25% dry content and spray-dried.
  • the dry powder had an astaxanthin content of 13.4% by weight.
  • the water-dispersed dry powder had a particle size of 220 nm and had an E 1/1 value of 111.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Nutrition Science (AREA)
  • Animal Husbandry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Birds (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Nanotechnology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Insects & Arthropods (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medical Informatics (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Biophysics (AREA)
  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)
  • Fodder In General (AREA)
  • Dairy Products (AREA)
  • Emulsifying, Dispersing, Foam-Producing Or Wetting Agents (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • General Preparation And Processing Of Foods (AREA)

Abstract

La présente invention concerne des suspensions aqueuses, contenant a) au moins une substance active difficilement soluble dans l'eau ou insoluble dans l'eau, b1) une protéine de petit-lait et/ou b2) un hydrolysat de protéine de petit-lait et c) un ester d'acide gras de saccharose présentant une valeur HLB (balance hydrophile-lipophile) comprise entre 10 et 18. Cette invention concerne également un procédé de production desdites suspensions ainsi que des poudres dérivées de ces dernières. Ces poudres et ces suspensions peuvent être utilisées comme additifs dans des produits alimentaires, des compléments alimentaires, des produits de fourrage pour animaux ainsi que des préparations cosmétiques et pharmaceutiques.
EP06763992A 2005-07-04 2006-06-30 Suspensions aqueuses de substances actives difficilement solubles dans l'eau ou insolubles dans l'eau et poudres seches produites a partir des dites suspensions Withdrawn EP1901619A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102005031468A DE102005031468A1 (de) 2005-07-04 2005-07-04 Wässrige Suspensionen schwer wasserlöslicher oder wasserunlöslicher Wirkstoffe und daraus hergestellte Trockenpulver
PCT/EP2006/063739 WO2007003598A1 (fr) 2005-07-04 2006-06-30 Suspensions aqueuses de substances actives difficilement solubles dans l'eau ou insolubles dans l'eau et poudres seches produites a partir desdites suspensions

Publications (1)

Publication Number Publication Date
EP1901619A1 true EP1901619A1 (fr) 2008-03-26

Family

ID=37054572

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06763992A Withdrawn EP1901619A1 (fr) 2005-07-04 2006-06-30 Suspensions aqueuses de substances actives difficilement solubles dans l'eau ou insolubles dans l'eau et poudres seches produites a partir des dites suspensions

Country Status (9)

Country Link
US (1) US20080220071A1 (fr)
EP (1) EP1901619A1 (fr)
JP (1) JP2008544973A (fr)
CN (1) CN101217885A (fr)
DE (1) DE102005031468A1 (fr)
MX (1) MX2008000010A (fr)
NO (1) NO20076665L (fr)
TW (1) TW200738326A (fr)
WO (1) WO2007003598A1 (fr)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070190130A1 (en) * 2006-02-16 2007-08-16 Mark William A Protein hydrolysate excipients
ATE501644T1 (de) * 2007-01-16 2011-04-15 Basf Se Flüssige formulierungen enthaltend carotinoide
JP5150176B2 (ja) * 2007-09-07 2013-02-20 富士フイルム株式会社 粉末組成物
WO2009048120A1 (fr) * 2007-10-11 2009-04-16 Nisshin Pharma Inc. Composition hydrosoluble renfermant de l'astaxanthine
EP2216015A4 (fr) * 2007-11-02 2012-12-19 So Pharmaceutical Corp Produit complexe de substance médiocrement soluble-agent tensio-actif, et son procédé de fabrication
JP2011507518A (ja) 2007-12-20 2011-03-10 アボット・ラボラトリーズ 安定な栄養粉末
JP5485879B2 (ja) * 2008-05-15 2014-05-07 株式会社ココカラファインネクスト 異なる物性の薬物の一剤形化
WO2010077137A1 (fr) * 2008-12-29 2010-07-08 Stichting Top Institute Food And Nutrition Particules de protéine et leur utilisation dans des aliments
US9775819B2 (en) * 2009-09-16 2017-10-03 R.P. Scherer Technologies, Llc Oral solid dosage form containing nanoparticles and process of formulating the same using fish gelatin
JP5600513B2 (ja) * 2010-07-29 2014-10-01 理研ビタミン株式会社 クロセチン製剤の製造方法
EP2716164B1 (fr) * 2011-05-26 2018-07-04 Kaneka Corporation Additif et procédé pour la fabrication d'une composition de produit alimentaire émulsifié huile-dans-eau
CN102488186B (zh) * 2011-12-06 2013-08-21 江南大学 一种无需高压均质的可食性纳米级β-胡萝卜素乳状液及其制备方法
RU2712165C2 (ru) * 2014-08-01 2020-01-24 Фирмениш Са Твердая дисперсия амидных пищевых ароматизаторов
DK3256002T3 (da) * 2015-02-09 2020-12-14 Frieslandcampina Nederland Bv Fremgangsmåde til fremstilling af en vandig dispersion af et svært dispergerbart planteprotein
US20180055788A1 (en) * 2015-03-19 2018-03-01 Basf Se Astaxanthin compositions (iv)
JP6604755B2 (ja) * 2015-06-30 2019-11-13 富士フイルム株式会社 液体食品組成物
JP6836440B2 (ja) * 2017-03-27 2021-03-03 第一工業製薬株式会社 粉末乳化剤組成物、粉末乳化剤組成物の製造方法、粉末乳化剤組成物を含む食品
CN111163859B (zh) * 2017-11-02 2022-10-28 三荣源有限公司 水溶性或水分散性微粒的制造方法、用途或使用方法
CN111714466A (zh) * 2019-03-18 2020-09-29 浙江医药股份有限公司新昌制药厂 一种高生物利用度高稳定性的类胡萝卜素制剂的制备方法

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3110598A (en) * 1959-09-08 1963-11-12 Hoffmann La Roche Process of making a carotenoid preparation
DE3119383A1 (de) * 1981-05-15 1982-12-02 Basf Ag, 6700 Ludwigshafen Verfahren zur herstellung von feinverteilten, pulverfoermigen carotinodpraeparaten
US4762995A (en) * 1984-06-22 1988-08-09 Georgia Tech Research Corporation Monodisperse aerosol generator
AU651626B2 (en) * 1990-10-24 1994-07-28 Nestec S.A. Medical foods having soluble fiber
US5634563A (en) * 1995-11-28 1997-06-03 Peng; Jung-Ching CD storage rack
DE19651681A1 (de) * 1996-12-12 1998-06-18 Basf Ag Stabile, wäßrige Dispersionen und stabile, wasserdispergierbare Trockenpulver von Xanthopyllen, deren Herstellung und Verwendung
JP3662445B2 (ja) * 1999-06-30 2005-06-22 花王株式会社 油中水型乳化油脂組成物
CA2380451C (fr) * 2000-05-30 2010-03-30 Societe Des Produits Nestle S.A. Composition primaire contenant un compose bioactif lipophile
US7097868B2 (en) * 2001-08-23 2006-08-29 Bio-Dar Ltd. Stable coated microcapsules
US20030175364A1 (en) * 2002-03-01 2003-09-18 Jerry Newman Process for binding carotenoids to proteins and the products thereof
EP1541042B1 (fr) * 2002-07-29 2006-05-17 Otsuka Pharmaceutical Co., Ltd. Composition de boisson sous forme gelifiee

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2007003598A1 *

Also Published As

Publication number Publication date
NO20076665L (no) 2008-02-27
MX2008000010A (es) 2008-04-04
DE102005031468A1 (de) 2007-01-18
CN101217885A (zh) 2008-07-09
WO2007003598A1 (fr) 2007-01-11
TW200738326A (en) 2007-10-16
US20080220071A1 (en) 2008-09-11
JP2008544973A (ja) 2008-12-11

Similar Documents

Publication Publication Date Title
EP1901619A1 (fr) Suspensions aqueuses de substances actives difficilement solubles dans l'eau ou insolubles dans l'eau et poudres seches produites a partir des dites suspensions
EP1794238B1 (fr) Procede de production de poudres seches d'un ou de plusieurs carotenoides
EP1898721B1 (fr) Procédé de production d'une suspension aqueuse et d'une préparation pulvérulente d'un ou de plusieurs caroténoïdes
EP2224823B2 (fr) Préparation pulvérulente de caroténoïde pour la coloration de boissons
EP0845503B1 (fr) Compositions de caroténoides liquides miscibles à l'huile
EP1575378B1 (fr) Formulations pulverulentes a base de phytosterols
EP2111125B1 (fr) Formulations liquides comprenant des carotenoides
WO2005075385A2 (fr) Procede de production de poudres seches d'un ou de plusieurs carotenoides
EP1228705A2 (fr) Procédé de préparation de poudres sèches d' un caroténoide ou plusieurs caroténoides
WO2008087139A1 (fr) Formulations huileuses
DE102005031467A1 (de) Emulgatorsystem, Emulsion und deren Verwendung
EP2403362B1 (fr) Compositions pulvérulentes de dérivés d'astaxanthine ii
EP2403360B1 (fr) Formulation de dérivés d'astaxanthine et leur utilisation iii
EP1761246A1 (fr) Dispersions aqueuses de principes actifs peu solubles dans l'eau et poudres seches produites a partir de ces dispersions
WO2006058671A1 (fr) Dispersions aqueuses d'un melange d'agents actifs difficilement solubles dans l'eau ou insolubles dans l'eau et d'une matiere proteique d'organisme unicellulaire

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: 20080204

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 NL PL PT RO SE SI SK TR

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: 20081231