DE10329685A1 - Microcapsules for use in detergents, rinsing or cleansing compositions or in production of pharmaceuticals, cosmetics or food supplements contain neurotransmitters or their precursors - Google Patents

Abstract

Core/shell microcapsules of average diameter 0.0005-5 mm contain endorphines, enkaphalines and/or dynorphins or their precursors or substances which release such compounds. Independent claims are also included for production of such microcapsules of average diameter 0.0001-5 mm and with a shell and an actives-containing matrix by (1) using gel-formers, chitosans and the active compounds or their precursors or substances which release such compounds to form a matrix; optionally dispersing the matrix in an oil phase; and treating the dispersed matrix with aqueous solutions of anionic polymers and optionally separating off the oil phase; (2) proceeding as per method (1) but replacing the chitosan in the first step with anionic polymers and replacing the anionic polymers in the third step by aqueous chitosan solutions; (3) using gel-formers and the active compounds or their precursors or substances which release such compounds to form a matrix; treating the matrix with a cationic polymer solution; and adjusting the pH of the mixture to above the pK s value of the cationic polymer; (4) processing the active compounds or their precursors or substances which release such compounds with oil bodies in presence of emulsifiers to form O/W emulsions; treating the emulsions with aqueous solutions of anionic polymers; contacting the matrix obtained with aqueous cationic polymer solutions; and separating the microcapsules from the aqueous phase; (5) covering the active compounds or their precursors or substances which release such compounds with layers of differently charged polyelectrolytes (i.e. by layer-by-layer technology).

Description

Territory of invention

The Invention is in the field of detergents and cleaners as well as the cosmetics and concerns new microcapsules with a content on special messengers, processes for their production and their use in different areas.

Of the Average consumer has become accustomed to the things of the daily Life resistant to be able to meet growing demands. A detergent should then not alone remove the stains from the shirt, it should also improve the comfort. A shampoo should not only clean the hair, but give the hairstyle shine and strength and the curls a special jumping ability. Women's tights should not only have fine silk shine, but also take care of your legs. That's the way to go continue the list as you wish. In sum, it's about products An additional Values, the so-called "added to give value, So just the certain "plus" that the buyer with his purchase and for that he u.U. also willing to pay more. It's only natural that at the thought, which additional Properties are desired by the consumer, strengthened current trends back is seized. One of the megatrends of the first decade of the 3rd Millennium is described by the keyword "wellness." At a time when On the one hand, people are getting older and older and enjoy their retirement can, on the other hand but the competition - sometimes the struggle for existence - always harder Relaxation becomes increasingly important. Not everyone however, has time and opportunity to contribute to the salvation daily To be able to seek massage or Ayurveda, things remain of the daily Life, such as washing, cleaning and ironing, usually not with relaxation, but rather be associated with the exact opposite.

The Object of the present invention has now been this To remedy maladministration and to show a way, as well as usually unpopular activities like ironing or Cleaning something positive can be won. Another task has consisted of means of daily life, such as washing, Cleaning and cleaning preparations, but also textiles, cosmetics and to improve food additives in their composition so that the consumer in their application a sense of satisfaction and the Relaxation feels.

description the invention

object of the invention are microcapsules with a mean diameter from 0.0005 to 5 mm consisting of a core and a shell that is characterized in that they include endorphins, enkephalins and / or dynorphins, whose precursors or releasing substances contain them.

The Addition of endorphins or similar Messenger-loaded microcapsules released during use and are perceived and perceived by the human neuroreceptors, make it possible, both conventional household products as well as cosmetics and functional nutritional supplements a new quality add, which is directly linked to the "wellness feeling" desired by the customer Encapsulation allows the chemically very unstable messenger substances reliable against external influences too protect, especially the chitosan encapsulation offers the advantage that interactions with other components of the capsule are avoided and the envelope substance even in many applications contributes beneficial properties while using Help the layer-by-layer technology capsules with a defined Hardness can be produced are by incorporating anchor materials in the shell particularly easy to fibers be liable.

microcapsules

The term "microcapsule" or "nanocapsule" is understood by those skilled spherical aggregates having a diameter in the range of about 0.0001 to about 5 and preferably 0.005 to 0.5 mm, containing at least one solid or liquid core, of at least More specifically, they are finely dispersed liquid or solid phases encased in film-forming polymers, the production of which is reflected on the material to be coated after emulsification and coacervation or interfacial polymerization, or melted waxes in a matrix recorded ("microsponge"), which may be additionally enveloped as microparticles with film-forming polymers. According to a third method, particles are alternately coated with polyelectrolytes of different charge ("layer-by-layer" method) .The microscopically small capsules can be dried like powders, in addition to mononuclear microcapsules, multinuclear aggregates, also called microspheres, are known or contain more cores distributed in the continuous shell material, and one or more microcapsules may also be enclosed by an additional second, third, etc. shell be. The shell may be made of natural, semi-synthetic or synthetic materials. Natural shell materials are, for example, gum arabic, agar-agar, agarose, maltodextrins, alginic acid or its salts, for example sodium or calcium alginate, fats and fatty acids, cetyl alcohol, collagen, chitosan, lecithins, gelatin, albumin, shellac, polysaccharides, such as starch or Dextran, polypeptides, protein hydrolysates, sucrose and waxes. Semi-synthetic shell materials include chemically modified celluloses, in particular cellulose esters and ethers, for example cellulose acetate, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and carboxymethylcellulose, and also starch derivatives, in particular starch ethers and esters. Synthetic envelope materials are, for example, polymers such as polyacrylates, polyamides, polyvinyl alcohol or polyvinylpyrrolidone.

Examples for microcapsules of the prior art are the following commercial products (in parenthesis the shell material is indicated in each case): Hallcrest Microcapsules (gelatin, gum arabic), Coletica thalaspheres (marine collagen), Lipotec Millicapseln (alginic acid, agar-agar), Induchem Unispheres (lactose, microcrystalline cellulose, hydroxypropylmethylcellulose); Unicerin C30 (lactose, microcrystalline cellulose, hydroxypropyl methylcellulose), Kobo Glycospheres (modified starch, fatty acid esters, phospholipids), softspheres (modified Agar-agar) and cow's probiol nanospheres (phospholipids) as well as primaspheres and prima ponges (chitosan, alginates) and primasys (phospholipids).

• (a1) aus Gelbildnern, kationischen Polymeren und Wirkstoffen eine Matrix zubereitet,
• (a2) gegebenenfalls die Matrix in einer Ölphase dispergiert,
• (a3) die dispergierte Matrix mit wässrigen Lösungen anionischer Polymere behandelt und gegebenenfalls dabei die Ölphase entfernt. oder
• (b1) aus Gelbildnern, anionischen Polymeren und Wirkstoffen eine Matrix zubereitet,
• (b2) gegebenenfalls die Matrix in einer Ölphase dispergiert,
• (b3) die dispergierte Matrix mit wässrigen Kationpolymerlösungen behandelt und gegebe nenfalls dabei die Ölphase entfernt; oder
• (c1) aus Gelbildnern und Wirkstoffen eine Matrix zubereitet,
• (c2) die Matrix mit einer Kationpolymerlösung versetzt und
• (c3) die Mischung auf einen pH-Wert einstellt der oberhalb des pK_s-Wertes des Kationpo lymers liegt; oder
• (d1) wässrige Wirkstoffzubereitungen mit Ölkörpern in Gegenwart von Emulgatoren zu O/W-Emulsionen verarbeitet,
• (d2) die so erhaltenen Emulsionen mit wässrigen Lösungen anionischer Polymere behandelt,
• (d3) die so erhaltene Matrix mit wässrigen Kationpolymerlösungen in Kontakt bringt und
• (d4) die so erhaltenen Verkapselungsprodukte von der wässrigen Phase abtrennt; oder

den Wirkstoff abwechselnd mit Schichten aus unterschiedlich geladenen Polyelektrolyten einhüllt (layer-by-layer-Technologie).Chitosan microcapsules and processes for their preparation are the subject of prior patent applications by the Applicant [WO 01/01926, WO 01/01927, WO 01/01928, WO 01/01929]. Microcapsules with average diameters in the range of 0.0001 to 5, preferably 0.001 to 0.5 and in particular 0.005 to 0.1 mm, consisting of an enveloping membrane and a matrix containing the active ingredients can be obtained, for example, by

• (a1) preparing a matrix from gelling agents, cationic polymers and active substances,
• (a2) optionally dispersing the matrix in an oil phase,
• (a3) treating the dispersed matrix with aqueous solutions of anionic polymers and optionally removing the oil phase. or
• (b1) preparing a matrix from gelling agents, anionic polymers and active substances,
• (b2) optionally dispersing the matrix in an oil phase,
• (b3) treating the dispersed matrix with aqueous cationic polymer solutions and optionally removing the oil phase; or
• (c1) preparing a matrix from gelling agents and active substances,
• (c2) adding a cationic polymer solution to the matrix and
• (c3) adjusting the mixture to a pH above the pK _s value of the cation polymer; or
• (d1) processed aqueous preparations of active substances with oil bodies in the presence of emulsifiers to O / W emulsions,
• (d2) treating the emulsions thus obtained with aqueous solutions of anionic polymers,
• (d3) contacting the resulting matrix with aqueous cationic polymer solutions, and
• (d4) separating the resulting encapsulated products from the aqueous phase; or

the active ingredient is alternately coated with layers of differently charged polyelectrolytes (layer-by-layer technology).

• gelling agent

in the According to the invention, the gelling agents are preferably those substances taking into account the characteristic in aqueous Solution at Temperatures above 40 ° C To form gels. Typical examples are heteropolysaccharides and Proteins. As thermogelling heteropolysaccharides are preferably Agaroses in the form of the agar-agar to be extracted from red algae also together with up to 30% by weight of non-gel forming agaropectins may be present. Main component the agaroses are linear polysaccharides of D-galactose and 3,6-anhydro-L-galactose, the alternating β-1,3- and β-1,4-glycosidic connected are.

The Heteropolysaccharides preferably have a molecular weight in the range of 110,000 to 160,000 and are both color and tasteless. Alternatives include pectins, xanthans (also xanthan Gum) and their mixtures in question. There are still such types preferred, which form gels in 1 wt .-% aqueous solution, not below 80 ° C melt and re-solidify above 40 ° C. From the Group of thermogeling proteins are exemplified by the various Called gelatin types.

• cationic polymers

Suitable cationic polymers are, for example, cationic cellulose derivatives such as a quaternized hydroxyethylcellulose, sold under the name Polymer JR 400 from Amerchol he ^® is hältlich, cationic starch, copolymers of diallyl ammonium salts and acrylamides, quaternized vinylpyrrolidone / vinylimidazole polymers, for example Luviquat ^® (BASF), condensation products of polyglycols and amines, quaternized collagen polypeptides such as, for example, Lauryldimonium Hydroxypropyl Hydrolyzed Collagen (Lamequat® ^® L / Grunau), quaternized wheat polypeptides, polyethyleneimine, cationic silicone polymers, for example amodimethicones, copolymers of adipic acid and dimethylaminohydroxypropyl diethylenetriamine (Cartaretine ^® / Sandoz), copolymers of acrylic acid with dimethyldiallylammonium chloride (Merquat ^® 550 / Chemviron), polyaminopolyamides and crosslinked water-soluble polymers thereof, cationic chitin derivatives such as quaternized chitosan , optionally microcrystalline, condensation products of dihaloalkylene, such as dibromobutane with bis-dialkylamines, such as bis-dimethylamino-1,3-propane, cationic guar gum, such as Jaguar ^® CBS, Jaguar ^® C-17 , Jaguar ^® C-16 of Celanese, quaternized ammonium salt polymers, for example Mirapol ^® A-15, Mirapol ^® AD-1, Mirapol ^® AZ-1 from Miranol.

Preferably, chitosan is used as the encapsulating material. Chitosans are biopolymers and are counted among the group of hydrocolloids. Chemically, they are partially deacetylated chitins of different molecular weight containing the following - idealized - monomer unit:

in the Contrary to most hydrocolloids, which are biological pH values are negatively charged, put chitosans under these conditions cationic biopolymers. The positively charged chitosans can with oppositely charged surfaces interact and are therefore used in cosmetic hair and personal care products and pharmaceutical preparations used. For the production chitosans are taken from chitin, preferably peel residues from crustaceans made as cheap raw materials in large quantities to disposal stand. The chitin is thereby in a procedure, the first of Hackmann et al. has been described, usually first by Addition of bases deproteinated, demineralized by the addition of mineral acids and finally through Addition of strong bases deacetylated, the molecular weights over a broad spectrum can be distributed. Preferably, such types are used as the average Molecular weight of 10,000 to 500,000 or 800,000 to 1,200,000 Dalton and / or have a Brookfield viscosity (1 wt .-% strength in glycolic acid) below 5000 mPas, a degree of deacetylation in the range of Have 80 to 88% and an ash content of less than 0.3 wt .-%. Because of better water solubility The chitosans are usually in the form of their salts, preferably used as glycolates.

• oil phase

The matrix may optionally be dispersed in an oil phase prior to the formation of the membrane. As oils for this purpose, for example, Guerbet alcohols based on fatty alcohols having 6 to 18, preferably 8 to 10 carbon atoms, esters of linear C ₆ -C ₂₂ fatty acids with linear C ₆ -C ₂₂ fatty alcohols, esters of branched C ₆ -C ₁₃ carboxylic acids with linear C ₆ -C ₂₂ -fatty alcohols, such as myristyl myristate, myristyl palmitate, myristyl stearate, Myristylisostearat, myristyl, Myristylbehenat, Myristylerucat, cetyl myristate, cetyl palmitate, cetyl stearate, Cetylisostearat, cetyl oleate, cetyl behenate, Cetylerucat, Stearylmyristat, stearyl palmitate, stearyl stearate, Stearylisostearat , stearyl oleate, stearyl behenate, Stearylerucat, isostearyl, isostearyl palmitate, Isostearylstearat, isostearyl isostearate, Isostearyloleat, isostearyl behenate, Isostea ryloleat, Oleyhnyristat, oleyl palmitate, oleyl stearate, oleyl isostearate, oleyl oleate, Oleylbehenat, oleyl erucate, behenyl myristate, behenyl palmitate, behenyl, Behenylisostearat, behenyl oleate, behenyl behenate, Behenyler ucat, erucyl myristate, erucyl palmitate, erucyl stearate, erucyl isostearate, erucyl oleate, erucyl behenate and erucyl erucate. In addition, esters of linear C ₆ -C ₂₂ fatty acids with branched alcohols, in particular 2-ethylhexanol, esters of hydroxycarboxylic acids with linear or branched C ₆ -C ₂₂ fatty alcohols, in particular dioctyl malates, esters of linear and / or branched fatty acids with polyhydric alcohols (such as propylene glycol, dimerdiol or trimer triol) and / or Guerbet alcohols, triglycerides based on C ₆ -C ₁₀ fatty acids, liquid mono- / di- / triglyceride mixtures based on C ₆ -C ₁₈ fatty acids, esters of C ₆ -C ₂₂ -fatty alcohols and / or Guerbet alcohols with aromatic carboxylic acids, in particular benzoic acid, esters of C ₂ -C ₁₂ -dicarboxylic acids with linear or branched alcohols having 1 to 22 carbon atoms or polyols having 2 to 10 carbon atoms and 2 to 6 hydroxyl groups, vegetable oils, branched primary alcohols, substituted cyclohexanes, linear and branched C ₆ -C ₂₂ fatty alcohol carbonates, guerbet carbonates, esters of benzoic acid with li -linear and / or branched C ₆ -C ₂₂ alcohols (such as Finsolv ^® TN, linear or branched, symmetrical or asymmetrical dialkyl ethers having 6 to 22 carbon atoms per alkyl group, ring opening products of epoxidized Fettsäureestern with polyols, silicone oils and / or aliphatic or naphthenic hydrocarbons , such as squalane, squalene or dialkylcyclohexanes.

• anionic polymers

The anionic polymers have the task of forming membranes with the chitosans. Salts of alginic acid are preferably suitable for this purpose. Alginic acid is a mixture of carboxyl-containing polysaccharides with the following idealized monomer unit:

The average molecular weight of the alginic acids or alginates in the range of 150,000 to 250,000. Both are salts of alginic acid their complete as well as their partial neutralization products, in particular the alkali metal salts and below this preferably the sodium alginate ("Algin") and the ammonium and Alkaline earth metal salts. especially preferred are mixed alginates, e.g. Sodium / magnesium or sodium / calcium alginates. In an alternative embodiment the invention come for However, anionic chitosan derivatives, e.g. carboxylation and especially succinylation products in question. Alternatively come also poly (meth) acrylates with average molecular weights in the range of 5,000 to 50,000 daltons as well as the various carboxymethylcelluloses in question. Instead of anionic polymers can be used for the formation of the envelope membrane also anionic surfactants or low molecular weight inorganic salts, such as For example, pyrophosphates are used.

• emulsifiers

• • Anlagerungsprodukte von 2 bis 30 Mol Ethylenoxid und/oder 0 bis 5 Mol Propylenoxid an lineare Fettalkohole mit 8 bis 22 C-Atomen, an Fettsäuren mit 12 bis 22 C-Atomen, an Alkylphenole mit 8 bis 15 C-Atomen in der Alkylgruppe sowie Alkylamine mit 8 bis 22 Kohlenstoffatomen im Alkylrest;
• • Alkyl- und/oder Alkenyloligoglykoside mit 8 bis 22 Kohlenstoffatomen im Alk(en)ylrest und deren ethoxylierte Analoga;
• • Anlagerungsprodukte von 1 bis 15 Mol Ethylenoxid an Ricinusöl und/oder gehärtetes Ricinusöl;
• • Anlagerungsprodukte von 15 bis 60 Mol Ethylenoxid an Ricinusöl und/oder gehärtetes Ricinusöl;
• • Partialester von Glycerin und/oder Sorbitan mit ungesättigten, linearen oder gesättigten, verzweigten Fettsäuren mit 12 bis 22 Kohlenstoffatomen und/oder Hydroxycarbonsäuren mit 3 bis 18 Kohlenstoffatomen sowie deren Addukte mit 1 bis 30 Mol Ethylenoxid;
• • Partialester von Polyglycerin (durchschnittlicher Eigenkondensationsgrad 2 bis 8), Polyethylenglycol (Molekulargewicht 400 bis 5000), Trimethylolpropan, Pentae rythrit, Zuckeralkoholen (z.B. Sorbit), Alkylglucosiden (z.B. Methylglucosid, Butylglucosid, Laurylglucosid) sowie Polyglucosiden (z.B. Cellulose) mit gesättigten und/oder ungesättigten, linearen oder verzweigten Fettsäuren mit 12 bis 22 Kohlenstoffatomen und/oder Hydroxycarbonsäuren mit 3 bis 18 Kohlenstoffatomen sowie deren Addukte mit 1 bis 30 Mol Ethylenoxid;
• • Mischester aus Pentaerythrit, Fettsäuren, Citronensäure und Fettalkohol und/oder Mischester von Fettsäuren mit 6 bis 22 Kohlenstoffatomen, Methylglucose und Polyolen, vorzugsweise Glycerin oder Polyglycerin.
• • Mono-, Di- und Trialkylphosphate sowie Mono-, Di- und/oder Tri-PEG-alkylphosphate und deren Salze;
• • Wollwachsalkohole;
• • Polysiloxan-Polyalkyl-Polyether-Copolymere bzw. entsprechende Derivate;
• • Block-Copolymere z.B. Polyethylenglycol-30 Dipolyhydroxystearate;
• • Polymeremulgatoren, z.B. Pemulen-Typen (TR-1, TR-2) von Goodrich;
• • Polyalkylenglycole,
• • Glycerincarbonat,
• • aliphatische Fettsäuren mit 12 bis 22 Kohlenstoffatomen, wie beispielsweise Palmitinsäure, Stearinsäure oder Behensäure, sowie Dicarbonsäuren mit 12 bis 22 Kohlenstoffatomen, wie beispielsweise Azelainsäure oder Sebacinsäure, sowie
• • Betaine wie die N-Alkyl-N,N-dimethylammoniumglycinate, beispielsweise das Kokosalkyldimethylammoniumglycinat, N-Acylaminopropyl-N,N-dimethylammoniumglycinate, beispielsweise das Kokosacylaminopropyldimethyl-ammoniumglycinat, und 2-Alkyl-3-carboxylmethyl-3-hydroxyethylimidazoline mit jeweils 8 bis 18 C-Atomen in der Alkyl- oder Acylgruppe sowie das Kokosacylaminoethylhydroxyethylcarboxymethylglycinat.

Suitable emulsifiers are anionic, amphoteric, cationic or, preferably, nonionic surface-active compounds from at least one of the following groups:

• Addition products of 2 to 30 moles of ethylene oxide and / or 0 to 5 moles of propylene oxide to linear fatty alcohols having 8 to 22 carbon atoms, to fatty acids having 12 to 22 carbon atoms, to alkylphenols having 8 to 15 carbon atoms in the alkyl group and Alkylamines having 8 to 22 carbon atoms in the alkyl radical;
• • alkyl and / or alkenyl oligoglycosides having 8 to 22 carbon atoms in the alk (en) yl radical and their ethoxylated analogs;
• Adducts of 1 to 15 moles of ethylene oxide with castor oil and / or hydrogenated castor oil;
• Adducts of 15 to 60 moles of ethylene oxide with castor oil and / or hydrogenated castor oil;
• Partial esters of glycerol and / or sorbitan with unsaturated, linear or saturated, branched fatty acids having 12 to 22 carbon atoms and / or hydroxycarboxylic acids having 3 to 18 carbon atoms and their adducts with 1 to 30 moles of ethylene oxide;
• Partial esters of polyglycerol (average intrinsic condensation degree 2 to 8), polyethylene glycol (molecular weight 400 to 5000), trimethylolpropane, pentae rythritol, sugar alcohols (eg sorbitol), alkylglucosides (eg methylglucoside, butylglucoside, laurylglucoside) and polyglucosides (eg cellulose) with saturated and / or or unsaturated, linear or branched fatty acids having 12 to 22 carbon atoms and / or hydroxycarboxylic acids having 3 to 18 carbon atoms and their adducts with 1 to 30 moles of ethylene oxide;
• Mixed esters of pentaerythritol, fatty acids, citric acid and fatty alcohol and / or mixed esters of fatty acids having 6 to 22 carbon atoms, methyl glucose and polyols, preferably glycerol or polyglycerol.
• Mono-, di- and trialkyl phosphates and mono-, di- and / or tri-PEG-alkyl phosphates and their salts;
• • wool wax alcohols;
• Polysiloxane-polyalkyl-polyether copolymers or corresponding derivatives;
• Block copolymers, for example polyethylene glycol-30 dipolyhydroxystearates;
• Polymer emulsifiers, eg Pemulen types (TR-1, TR-2) from Goodrich;
• Polyalkylene glycols,
• • glycerin carbonate,
• Aliphatic fatty acids having 12 to 22 carbon atoms, such as palmitic acid, stearic acid or behenic acid, and dicarboxylic acids having 12 to 22 carbon atoms, such as azelaic acid or sebacic acid, and
• Betaines such as the N-alkyl-N, N-dimethylammonium glycinates, for example the cocoalkyldimethylammonium glycinate, N-acylaminopropyl-N, N-dimethylammonium glycinates, for example the cocoacylaminopropyldimethylammonium glycinate, and 2-alkyl-3-carboxylmethyl-3-hydroxyethylimidazolines each having 8 to 18 C atoms in the alkyl or acyl group and the Kokosacylaminoethylhydroxyethylcarboxymethylglycinat.

• Production process microcapsules

For the preparation of the microcapsules is usually prepared from 1 to 10, preferably 2 to 5 wt .-% aqueous solution of the gelling agent, preferably the agar agar ago and heated them under reflux. In the boiling heat, preferably at 80 to 100 ° C, a second aqueous solution is added ben, which contains the cationic polymer, preferably the chitosan in amounts of 0.1 to 2, preferably 0.25 to 0.5 wt .-% and the active ingredients in amounts of 0.001 to 1 and in particular 0.01 to 0.1 wt. - contains%; this mixture is called a matrix. The loading of the microcapsules with active ingredients can therefore also amount to 0.001 to 1% by weight, based on the capsule weight, which is completely sufficient in view of the high activity of the messenger substances. If desired, water-insoluble constituents, for example inorganic pigments, can also be added at this time to adjust the viscosity, these being added as a rule in the form of aqueous or aqueous / alcoholic dispersions. To emulsify or disperse the active ingredients, it may also be useful to add emulsifiers and / or solubilizers to the matrix. After the preparation of the matrix of gelling agent, cationic polymer and active ingredients, the matrix can optionally be very finely dispersed in an oil phase under high shear in order to produce the smallest possible particles in the subsequent encapsulation. It has proved to be particularly advantageous to heat the matrix to temperatures in the range of 40 to 60 ° C, while the oil phase is cooled to 10 to 20 ° C. In the last, now again obligatory step, the actual encapsulation takes place, ie the formation of the enveloping membrane by contacting the cationic polymer in the matrix with the anionic polymers. For this purpose, it is recommended that the optionally dispersed in the oil phase matrix at a temperature in the range of 40 to 100, preferably 50 to 60 ° C with an aqueous, about 1 to 50 and preferably 10 to 15 wt .-% aqueous solution of the anion polymer to treat and, if necessary, at the same time or subsequently to remove the oil phase. The resulting aqueous preparations generally have a microcapsule content in the range of 1 to 10 wt .-%. In some cases, it may be advantageous if the solution of the polymers contains other ingredients, such as emulsifiers or preservatives. After filtration, microcapsules are obtained, which on average have a diameter in the range of preferably about 0.01 to 1 mm. It is recommended to sift the capsules to ensure the most even size distribution possible. The microcapsules thus obtained may have any shape in the production-related framework, but they are preferably approximately spherical. Alternatively, one can also use the anionic polymers for the preparation of the matrix and perform the encapsulation with the cationic polymers, especially the chitosans.

alternative If the encapsulation can also be carried out using cationic polymers, taking advantage of their property, at pHs above the to coagulate pKs value.

In A second alternative method is used to prepare the microcapsules of the invention will be first an O / W emulsion is prepared, which in addition to the oil body, water and the active ingredients contains an effective amount of emulsifier. For the preparation of the matrix This preparation is mixed with vigorous stirring with a suitable Amount of an aqueous anionic polymer added. The membrane formation takes place by adding the chitosan solution. Of the entire process preferably occurs in the weakly acidic region pH = 3 to 4 instead. If necessary, the pH is adjusted by Addition of mineral acid. After membrane formation, the pH is raised to 5 to 6, for example by Add triethanolamine or another base. Here comes it causes an increase in the viscosity, by adding further thickening agents, e.g. polysaccharides especially xanthan gum, Guar guar, agar-agar, alginates and tyloses, carboxymethylcellulose and hydroxyethyl cellulose, higher molecular weight Polyethylene glycol mono- and diesters of fatty acids, polyacrylates, polyacrylamides and the like still supported can be. Finally For example, the microcapsules of the aqueous phase separated by decantation, filtration or centrifugation.

In a third alternative method, the formation of the microcapsules is carried out around a preferably solid, for example, crystalline core by coating it in layers with oppositely charged polyelectrolytes. In this connection, see the European patent EP 1064088 B1 (Max Planck Society).

Endorphins, enkephalins and dynorphins

Endorphins, enkephalins or dynorphines, their precursors and substances which release them ("endorphin pusher") are considered as active ingredients for the loading of the microcapsules. The term endorphin is understood to mean an endogenous and morphine-derived collective name for painkillers and endorphins The structure of the endorphins shows a close correspondence with the enkephalins and dynorphines occasionally counted to the same group, and there is also a close biogenetic relationship to the peptide hormones ACTH, lipotropin, which are physiologically active at quite different sites of action and melanotropin β-lipotropin, the precursor of the α-, β- and γ-endorphins, results from the prohormone proopiomelanocortin (POMC, MW 29,000) in addition to ACTH and α-melanotropin, whereas the enkephalins are derived from preproenkephalin, β-neo-endorphin and the dynorphins are formed from preprodynorphine w While the Enkephaline compares are easy to synthesize, the endorphins are recovered by cleavage of β-lipotropin between amino acids 60 and 61 (Arg and Tyr).

commercial applicability

The microcapsules according to the invention are characterized by the fact that they contain the messengers contained in them stable and release only at the predetermined location and time. They are therefore suitable for a variety of applications, for example in the field of washing, rinsing and cleaning agents, where they either by mechanical influence, such as manual rinsing or thermal stress, e.g. during the ironing be released. Typical agents containing the microcapsules are next to detergents and Ironing sprays also detergents and especially Softener, since the capsules dependent on of their diameter also attach to the fibers and so during the Break open and release the messenger substances. Conversely, the Fibers, yarns as well as the finished textiles also directly with equipped with the microcapsules become, for example by forced application after the Fuller procedure. In a further embodiment of the invention, the Microcapsules also for the production of cosmetic and pharmaceutical Preparations are used. Typical examples are hair shampoos or facial creams, in which the messenger substances by mechanical Exposure to be released. Since it concerns with the active ingredients endogenous Products, can the microcapsules - in dependence from the encapsulation material - too used for the production of food additives, such as sports nutrition, fitness drinks and the like. Here, the release then takes place through the absorption via the Stomach. The proportion of microcapsules in the end products can via a vary widely and is typically 0.1 to 10, preferably 1 to 10 and in particular 2 to 5 wt .-%.

example 1

In a 250 ml three-necked flask with stirrer and reflux condenser, 0.7 g of agar-agar were dissolved in 36.3 ml of boiling water and then treated with 25 g of a 2% strength by weight aqueous solution of sodium alginate. Thereafter, 15 g of polyethylene glycol (molecular weight 200) were added 0.5 g of Phenonip ^® (preservative mixture), 10 g glycerol, and 10 g of mineral oil, 0.16 g of tocopherol acetate and 0.1 g of β-lipotropin with intensive stirring. For encapsulating the matrix in an aqueous 1 wt .-% solution of chitosan glycolate (Hydagen HCMF ^®, Cognis) was added dropwise, the addition still contained 0.5 wt .-% calcium chloride. The resulting microcapsules had a mean diameter of 1 mm.

Example 2

In a 250 ml three-necked flask with stirrer and reflux condenser, 0.7 g of agar-agar were dissolved in 36.3 ml of boiling water and then treated with 25 g of a 2% strength by weight aqueous solution of sodium alginate. Thereafter, 15 g of polyethylene glycol (molecular weight 200), 0.5 g phenonip (preservative mixture), 10 g glycerol and 10 g mineral oil, 0.16 g tocopherol acetate and 0.25 g of a cleavage product of β-lipotropin between amino acids 60 and 61 under added to vigorous stirring. For encapsulating the matrix in an aqueous 1 wt .-% strength cationic polymer solution (Polyquart ^® 701 / N) was added dropwise, which additionally contained 0.5 wt .-% calcium chloride. The resulting microcapsules had a mean diameter of 1 mm.

Example 3

A mixture of 0.01 g of β-lipotropin in 5 ml of water was placed in a stirred flask and mixed with 0.5 g of corn starch. After vigorous stirring, the water was removed in vacuo and the solid residue with 5 g of a 0.1 wt .-% solution of chitosan glycolate (Hydagen CMF ^®, Cognis) were mixed. The preparation was stirred vigorously and 15 parts by weight of sodium hydroxide solution were added dropwise until neutral point. Subsequently, the product was freeze-dried. The microcapsules had a mean diameter of 75 microns.

Claims (10)

Microcapsules with a mean diameter of 0.0005 to 5 mm consisting of a core and a shell, characterized in that they contain endorphins, enkephalins and / or dynorphins, their precursors or releasing substances. A process for the preparation of microcapsules with mean diameters in the range of 0.0001 to 5 mm, consisting of an enveloping membrane and a matrix containing the active ingredients, comprising (a1) gelling agents, chitosans and active agents selected from the group being formed of endorphins, enkephalins and / or dynorphins whose precursors or releasing substances form a matrix, (a2) optionally dispersing the matrix in an oil phase, (a3) treating the dispersed matrix with aqueous solutions of anionic polymers and optionally while removing the oil phase; Process for the preparation of microcapsules with medium Diameters in the range of 0.0001 to 5 mm, consisting of a envelope membrane and a matrix containing the active ingredients in which (B1) selected from gelling agents, anionic polymers and active ingredients the group formed by endorphins, enkephalins and / or Dynorphins, their precursors or releasing substances, a Matrix prepared, (b2) optionally dispersing the matrix in an oil phase, (B3) the dispersed matrix with aqueous chitosan treated and optionally the oil phase removed; A process for the preparation of microcapsules with mean diameters in the range of 0.0001 to 5 mm, consisting of an enveloping membrane and a matrix containing the active ingredients, comprising (c1) gelling agents and active ingredients selected from the group consisting of endorphins, enkephalins and / or dynorphins, their precursors or releasing substances, a matrix prepared, (c2) enables the matrix with a cation polymer solution, and (c3) the mixture to a pH value adjusted is above the _pK a value of the cation polymer; Process for the preparation of microcapsules with medium Diameters in the range of 0.0001 to 5 mm, consisting of a envelope membrane and a matrix containing the active ingredients in which (D1) aqueous Preparations of active substances selected from the group formed is derived from endorphins, enkephalins and / or dynorphins, their precursors or releasing substances, with oil bodies in the presence of emulsifiers processed to O / W emulsions, (d2) the emulsions thus obtained with watery solutions treated with anionic polymers, (d3) the matrix thus obtained with watery Cation polymer solutions brings in contact and (d4) the encapsulation products thus obtained from the watery Phase separates; Process for the preparation of microcapsules with medium Diameters in the range of 0.0001 to 5 mm, consisting of a envelope membrane and a matrix containing the active ingredients, in which one active ingredients selected from the group formed by endorphins, enkephalins and / or dynorphins, their precursors or releasing substances, alternating with layers of differently charged polyelectrolytes envelops (Layer-by-layer technology). Use of microcapsules according to claim 1 for the preparation of washing, rinsing and cleaning agents. Use of microcapsules according to claim 1 for the equipment of Fibers, yarns and textiles. Use of microcapsules according to claim 1 for the preparation of cosmetic and / or pharmaceutical preparations. Use of microcapsules according to claim 1 for Production of food supplements.