EP1448296A1

EP1448296A1 - Gel capsules containing active ingredients and use thereof

Info

Publication number: EP1448296A1
Application number: EP02779555A
Authority: EP
Inventors: Michael Dreja; Claudia Klink; Andreas Buhl
Original assignee: Henkel AG and Co KGaA
Current assignee: Henkel AG and Co KGaA
Priority date: 2001-11-27
Filing date: 2002-11-14
Publication date: 2004-08-25
Also published as: DE10157755A1; JP2005510344A; US20040247664A1; WO2003045545A1; AU2002342907A1

Abstract

A method for the production of gel capsules charged with an active ingredient and/or additive in the form of matrix or storage systems containing active and/or additive agents and the use thereof are disclosed, in particular for application in the domains of cosmetics and bodycare, pharmaceuticals, adhesive processing and washing and cleaning agents.

Description

Gel capsules containing active ingredient and their use

The present invention relates to a method for producing gel capsules loaded with active substances and / or active substances. Furthermore, the present invention relates to the capsule systems produced in this way and their use.

For many products, it is attractive today for aesthetic reasons to add ingredients or active ingredients separately in a delimited form, e.g. B. in the form of capsules, balls, drops or as a second phase. In addition to the aesthetic advantages, such spatial delimitations often also show stability and formulation advantages.

Active ingredients or active substances such as fragrances, fragrance mixtures, fragrance preparations, essential oils, perfume oils and care oils, dyes or pharmaceutically active ingredients that are used in cosmetic and / or pharmaceutical products or in detergents and cleaning agents often lose during storage or directly applying their activity. Some of these substances can also have insufficient stability for use or cause interfering interactions with other product components.

It is therefore of interest to control such substances in a controlled manner and to use them at the desired location with maximum effect.

For this reason, active and / or active substances, such as. B. fragrances, fragrance mixtures, fragrance preparations, care oils and antibacterial agents, added to the products in a spatially defined, protected form. Sensitive substances are often enclosed in capsules of various sizes, adsorbed on suitable carrier materials or chemically modified. The release can then be activated with the aid of a suitable mechanism, for example mechanically by shearing, or can take place diffusively directly from the matrix material. Systems are therefore sought that are suitable as encapsulation, transport or presentation vehicles - often synonymously also referred to as "delivery systems" or "carrier systems".

There are already numerous commercial delivery systems based on porous polymer particles or liposomes (e.g. Mikrosponges® from Advanced Polymer Systems or Nanotopes® from Ciba-Geigy, see B. Herzog, K. Sommer, W. Baschong, J. Röding "Nanotopes ™; A Surfactant Resistant Carrier System" in SÖFW-Journal, 124th year 10/98, pages 614 to 623).

The disadvantage of these conventional delivery systems known from the prior art is that they have only a low loading potential, the particle size of the polymer spheres is usually in the range from a few micrometers to a few 100 μm and encapsulation of the active substances is generally not possible can be done situ. The modification of the capsule surfaces is not possible or very expensive. Liposomes also have insufficient stability for many applications.

Another disadvantage of these conventional systems is that the release of active substances can often not be controlled at the site of the specific application.

Another disadvantage of the conventional systems is that they do not allow a switching mechanism to be built into such encapsulations, with the aid of which a targeted release of the ingredients can take place.

Furthermore, in the production of active and / or active ingredient-loaded capsules according to the prior art, disturbing or toxic, malodorous or aggressive constituents are often incorporated into the formulation. The encapsulations are often carried out under aggressive conditions which stress the active ingredients to be encapsulated (high temperatures, long reaction times, the occurrence of free radicals, etc.). It is therefore an object of the present invention to provide a capsule system in the form of a matrix or depot system which contains active ingredients with properties which are improved compared to the prior art and a corresponding production process.

Another object of the present invention is the development, in particular, of capsules with a temperature switch or of sustained-release capsules with a long-term effect for the release of active substances, such as. B. fragrances, fragrance mixtures, fragrance preparations, care oils, vitamins, hydrophobic agents, antibacterial substances or other ingredients, and a corresponding manufacturing process. In particular, the method according to the invention should make it possible to produce capsules with a defined size, which contain active ingredients and which differ from the prior art in terms of their advantageous properties. The capsule production should in particular without a polymerization process, i. H. without the use of free radicals, which can destroy active substances.

In addition, the method according to the invention is said to have the advantage of being applicable to almost any, in particular hydrophobic, active ingredient. The resulting capsules should be as stable as possible, but should be able to release the ingredient as completely as possible in a simple manner. It is particularly advantageous if the ingredient from the capsule is released over a long period of time under the action of temperature or without the action of temperature when the product containing the capsule is used. This should take place as far as possible without additional mechanical intervention by the user. In addition, the proportion of auxiliary material (e.g. substances to form the capsule structure) should be as low as possible.

The present invention thus relates to a process for producing gel capsules loaded with active and / or active substance (s) in the form of active and / or active substance-containing matrix and / or depot systems, which is characterized by the following process steps: (a) providing a mixture of an active and / or active substance-containing oil phase and at least one block copolymer;

(b) providing a water / surfactant mixture;

(c) dispersing the mixtures prepared under (a) and (b), if appropriate with heating to temperatures above the gelation temperature of the resulting dispersion;

(d) optionally preparing a preemulsion and / or macroemulsion from the dispersion prepared under (c) with heating above the gelation temperature of the preemulsion and / or macroemulsion;

(e) Preparation of a mini emulsion starting from the dispersion obtainable under (c) or alternatively starting from the preemulsion and / or macroemulsion optionally prepared under (d) while heating to temperatures above the gelation temperature of the resulting emulsion;

(f) cooling the miniemulsion produced under (e) below its gel formation temperature, so that gel capsules loaded with active and / or active substances form in the form of active and / or active substance-containing matrix and / or depot systems; and

(g) optionally subsequent separation of the active or active substance-containing matrix and / or depot systems obtained in this way.

In the process according to the invention, the mixture of the at least one block copolymer and the active or active substance-containing oil phase can be provided by adding the block copolymer, in particular with stirring, with heating of the active or active substance-containing oil phase or vice versa. The heating temperature should be above the gelation temperature of the resulting mixture.

In the process according to the invention, either the active or active substance itself can be the oil phase or the active or active substance can be dissolved in a carrier oil. In the latter case, the carrier oil phase can be selected in particular be from the group of paraffin oils, isoparaffin oils, silicone oils, glycerides, triglycerides, naphthalene-containing oils, hydrocarbon-containing solvents and mixtures thereof. The carrier oil phase is preferably inert to the active and / or active ingredient and to the block copolymer. Inert means in particular that the carrier oil does not react with the active and / or active ingredient or block copolymer.

The ratio of the active or active ingredient used and the carrier oil which may be used can vary within wide limits. A quantity-based or weight-based ratio of active and / or active ingredient to carrier oil of 1: 99 to 99: 1 is possible.

In the process according to the invention, the dispersion can be prepared in step (c) in that the mixture prepared in step (a) from at least one block copolymer and an active or active substance-containing oil phase in the water / surfactant mixture prepared in step (b) is entered or vice versa.

The emulsification of the dispersion obtained under (c), optionally carried out in step (d) in the process according to the invention, can be carried out by the action of shear forces.

The production of the mini emulsion carried out in step (e) in the process according to the invention can also be carried out by the action of shear forces. This involves, for example, ultrasound treatment, high-pressure homogenization or microfluidizer treatment.

In the process according to the invention, the formation of the mini-emulsion in step (e) can be carried out under a homogenization pressure of 50 bar to 30,000 bar, preferably 300 bar to 2,500 bar. The miniemulsion can be formed in particular over a period of 10 seconds to 2 hours, preferably 1 minute to 20 minutes, depending on the volume of the miniemulsion. The formation of the mini emulsion generally does not take place spontaneously, but rather through the energy input; this can be done by one time or repeated homogenization take place. The homogenization process has in particular a throughput that depends on the size of the homogenizer; the treatment time of each emulsion droplet is only in the millisecond range.

In the process according to the invention, the cooling in step (f) leads to solidification, i.e. H. Gelation or gel formation of the active or active substance-laden oil droplets of the mini emulsion to form gel and active substance-loaded gel capsules in the form of matrix and / or depot systems, the mean particle sizes of which correspond to the oil phase droplets of the mini emulsion.

The gel formation in step (f) takes place in the process according to the invention in particular on the basis of physical interactions, in particular on the basis of physical network formation of the block copolymer molecules in the oil phase.

The miniemulsion used in the process according to the invention can in particular be an essentially aqueous emulsion, stabilized by a surfactant, of the block copolymer (s) and the active or active substance-containing oil phase. The emulsion obtained according to the invention preferably has an average particle size of the emulsified oil phase droplets of approximately 10 nm to approximately 600 nm, preferably approximately 20 nm to approximately 500 nm.

Mini emulsions are dispersions of an aqueous phase, an oil phase and optionally one or more surface-active substances, in which unusually small droplet sizes are realized. In other words, mini emulsions can thus be understood as aqueous dispersions of stable oil droplets with drop sizes of about 10 to about 600 nm, which are obtained by intensive shearing of a system which contains oil, water, a surfactant and a hydrophobic. The hydrophobes which are required for the production of stable miniemulsion are in the present case the block copolymer and / or the active or active substance-containing oil phase, which generally have a low water solubility. The hydrophobic suppresses the mass exchange between the different oil droplets by osmotic forces (Ostwald ripening), but immediately after the formation of the mini-emulsion, the dispersion is only critically stabilized with regard to collisions of the particles, and the drops themselves can still grow in size through further collisions and melting. This effect can be suppressed or reduced by the gel formation of the oil droplets.

In contrast to microemulsions, which can generally be regarded as thermodynamically stable and optically transparent emulsions with droplet sizes of generally about 2 to at most about 50 nm, which are prepared by mixing water, oil, surfactant and optionally cosurfactant, miniemulsions can be considered as kinetically stable and optically opaque to cloudy emulsions with droplet sizes of generally about 10 to about 600 nm are understood, which by mixing water, oil, surfactant and optionally a (further) hydrophobic (e.g. also an oil) by relative entry high amounts of shear energy are produced, the droplet size in the mini-emulsion being determined in particular by the energy input and the type and amount of the individual components, in particular the surfactants. In contrast to conventional emulsions, the droplet size distributions in mini emulsions are almost monodisperse. In general, mini emulsions - unlike microemulsions - are critically stabilized, i.e. H. a surfactant content is generally required which is just sufficient to stabilize the systems, in particular a surfactant content of less than 5% by weight, while in the case of microemulsions the required surfactant content is significantly higher at about 5 to 15% by weight , Furthermore, the interfacial tension in miniemulsions is significantly higher than that of microemulsions.

For further details regarding mini emulsions, reference is made to the article by K. Landfester, F. Tiarks, H.-P. Hentze, M. Antonietti "Polyaddition in miniemulsions: A new route to polymer dispersions" in Macromol. Chem. Phys. 201, 1-5 (2000), the contents of which are hereby incorporated by reference. Reference is also made to the document ED Sudol, MS Es-Aasser, referenced therein, in: "Emulsion Polymerization and Emulsion Polymers", PA Lovell, MS El-Aasser, Eds., Chichester 1997, p. 699, the contents of which are also hereby incorporated by reference is included. In process step (e) of the process according to the invention, the miniemulsion used according to the invention is therefore initially provided or produced. The microemulsion is prepared in a manner known per se. Reference can be made to the references already cited, namely the article by Landfester et al., The publication by Sudol et al. as well as on the published documents WO 98/02466, DE 196 28 142 A1, DE 196 28 143 A1 and EP 818471 A1, the entire content of which is hereby incorporated by reference.

To produce the miniemulsion, an aqueous preemulsion or macroemulsion which contains the active ingredients and / or the active ingredients, the block copolymer, the surfactant (surface-active substance) and water can first be prepared in a known manner.

After the mixture has been homogenized and optionally converted into a preemulsion or macroemulsion, the macroemulsion formed in this way is then converted into a so-called miniemulsion, a very stable type of emulsion, in a conventional manner known to those skilled in the art, e.g. B. by treatment of the previously generated macroemulsion by ultrasound, by high pressure homogenization or by a microfluidizer. The fine distribution of the components is generally achieved by a high local energy input.

The average size of the droplets of the disperse phase of the miniemulsion used according to the invention can generally be determined according to the principle of quasi-elastic dynamic light scattering, the so-called z-average droplet diameter of the unimodal analysis of the autocorrelation function being obtained here. The particle size and particle size distribution of the emulsified droplets in the mini emulsion finally also determine the particle size and particle size distribution of the end products or gel capsules and essentially coincides therewith. The gel capsules obtained can also be characterized with the aid of dynamic light scattering in terms of their particle size and monodispersity. The separation of the gel capsules loaded with active substance or active substance in step (g) in the process according to the invention can be carried out by conventional methods. In particular, this involves freeze drying (lyophilization), evaporation of the dispersant, ultrafiltration, dialysis or spray drying under gentle conditions.

In the process according to the invention, all process steps (a) to (e) can be carried out at temperatures above the gel formation temperature of the respective mixtures, dispersions and / or emulsions. In general, these temperatures can range from 20 ° C to 200 ° C, preferably from 50 ° to 95 ° C.

According to the invention, gels are understood to mean, in particular, organogels in the form of dimensionally stable, easily deformable, liquid-disperse systems composed of block copolymer (s) and oil phase (s). In the present case, these gels form quasi “sponge-like” structures from the block copolymer (s) as a gel former (gelling agent) or gelling agent and the active and / or active ingredient-containing oil phase as a dispersing agent. These "sponge-like" structures consist of a physical network, ie they form a network formed due to physical interactions. Gels have a yield point and are particularly elastically and / or plastically deformable. Below a gel formation temperature T _ge ι - also called the gelation temperature - which is characteristic of the respective gel, the combination of gelling agent and dispersant forms a gel-like structure (T <T _ge ι), while at temperatures above the gel formation temperature T _ge ι (T> T _ge ι) liquefied. Gels can also be described with the aid of their elastic modulus G 'and their loss modulus (dissipative module) G ": A combination of gelling agent and dispersant then forms a gel-like structure if, for a given oscillation or measuring frequency, the elastic modulus is greater than or equal to the loss modulus is (G '> G "), which is the case below the gel formation temperature Tgei. Above the gel formation temperature T _ge, the gel structure breaks down and the loss modulus is greater than the elastic modulus (G '<G "). According to the invention, the term gel capsules does not mean conventional capsules with core / shell structures, but rather a composite of block copolymer (s) formed as a gelling agent and active or active substance-containing oil phase (s) as a dispersing agent due to physical interactions, which are below their gel formation temperature form a "sponge-like" structure in the form of discrete, shell-free gel particles.

According to a preferred embodiment of the present invention, the method according to the invention is carried out as follows. First of all, the active or active substance phase is represented by a mixture of the oil phase and the gel former: The active and / or active substance (e.g. a fragrance) is heated and, if necessary, mixed with an inert, miscible carrier oil; A particularly hydrophobic gel former, preferably a block copolymer, which forms solid organogels with the oil phase below the relevant gel formation temperature (T _ge ι), is stirred into this warm mixture. The resulting mixture is melted _ge at a temperature above the gelling temperature T ι the resultant mixture and emulsified into a water / surfactant mixture the same temperature under vigorous stirring. The water / surfactant mixture is provided separately. The crude emulsion formed from the oil phase and block copolymer on the one hand and from water and surfactant on the other is converted into a mini emulsion using a high-pressure homogenizer at a pressure of 500 to 2,000 bar. This mini emulsion is characterized by the fact that it is particularly stable against Ostwald ripening and has a largely uniform particle size distribution. The cooling of the miniemulsion to temperatures which are below the gel formation temperature (T _ge ι) of the miniemulsion, preferably room temperature, then leads to a solidification of the capsule or particle content: the miniemulsion is agitated to a temperature below the gel formation temperature T _ge ι, which is preferably below room temperature, allowed to cool. The gel former gels the oil in the oil phase droplets and forms rigid, gel-like, shell-free capsules or particles. These particles have a size in the range from 10 nm to 600 nm. The gel capsule or particle dispersion according to the invention can now be processed further, eg. B. on Cleaning cloths applied or worked into a detergent or shampoo.

The active ingredient used in the process according to the invention is an oil-soluble, preferably hydrophobic active ingredient. The active and / or active ingredient can preferably be selected from the group of fragrances, fragrance mixtures and fragrance preparations; oils such as essential oils, perfume oils, care oils and silicone oils; Antioxidants and biologically active substances; oil-soluble vitamins and vitamin complexes; Enzymes and enzymatic systems; cosmetically active substances; substances active in washing and cleaning; Proteins and lipids; Waxing and fats; Foam inhibitors; Graying inhibitors and color protection agents; Soil repellent active ingredients; Bleach activators and optical brighteners; amines; Dyes, color pigments and / or coloring substances; and mixtures of the aforementioned compounds.

The active ingredients used according to the invention can, in particular, be essentially water-insoluble or at least sparingly soluble in the aqueous phase. In such a case, the active ingredients according to the invention are preferably less than 10%, preferably less than 5%, in particular less than 1% soluble in the aqueous phase.

The content of active ingredient (s) in the miniemulsion produced in step (e) can vary within wide limits. In general, it is 0.01% by weight to 50% by weight, preferably 2% by weight to 30% by weight. The content of block copolymer in the miniemulsion produced in step (e) can likewise vary within wide limits; it is in particular 0.01% by weight to 50% by weight, preferably 2% by weight to 20% by weight. If a carrier oil for the active and / or active ingredient is present, its content can likewise vary within wide ranges, in particular this content is in the range from 1% by weight to 50% by weight, preferably 2% by weight to 30% by weight. The water content used in the miniemulsion according to step (e) can also vary within wide limits. In general, it is 50% by weight to 99% by weight, preferably 70% to 90% by weight. The content of surfactant (s) in the miniemulsion produced in step (e) can also vary within wide limits. It amounts to 0.01% by weight to 10% by weight, preferably 0.5% by weight to 5% by weight.

The block copolymer used in the process according to the invention can be a particularly hydrophobic copolymer which forms a gel, preferably organogel, with the active and / or active substance-containing oil phase below the corresponding gel formation temperature. The block copolymer used according to the invention is therefore in particular a copolymer with oil-gelling properties

The block copolymer used in the process according to the invention can be a polymer (AB -...) _n (n = number of repeating units) consisting of at least two blocks or components A, B, ..., in which at least one the blocks are hard blocks and at least one other of the blocks is soft blocks. That is, The blocks differ in relation to each other by their hardness, which is expressed in particular by their glass transition temperatures.

The glass transition temperatures of the hard and soft blocks of the block copolymer should differ by at least 50 ° C, in particular at least 60 ° C, preferably at least 70 ° C.

In particular, the hard block may have a glass transition temperature Tg (art)> 20 ° C, particularly Tg (har _t) 50 ° C, preferably T _g (hard) 90 ° C., and the soft block has a glass transition temperature T _g _(wei c) ≤ 20 ° C, in particular T _g ( _We ich) ≤ 0 ° C, preferably Tg _{we ich) ≤- 45 ° C.

At least one block, preferably the hard block, of the block copolymer used in the process according to the invention should not be or only poorly oil-soluble or at most moderately oil-soluble, while at least one other block of the block copolymer, preferably the soft block, should be oil-soluble. In particular, at least one block of the block copolymer, preferably the hard block, less oil-soluble than at least one other block of the block copolymer, preferably the soft block.

The hard block of the copolymer can preferably be selected from the group of polystyrenes, poly (meth) acrylates, polycarbonates, polyesters, polyanilines, poly-p-phenylenes, polysulfone ethers, polyacrylonitriles, polyamides, polyimides, polyethers, polyvinyl chlorides and mixtures thereof. The soft block of the block copolymer can preferably be selected from the group of rubbers, in particular optionally substituted polyalkylenes, preferably polybutadienes, and mixtures of rubbers or polyalkylenes, such as polybutadiene-ethylene, polybutadiene-propylene, polyethylene ethylenes; polyvinyl alcohols; Polyalkylene glycols, such as polyethylene glycols and polypropylene glycols; Polydimethoxysiloxanen; Polyurethanes.

In particular, the block copolymer can be selected from styrene / alkylene block copolymers, wherein the (poly) alkylene block can also be a mixed block, as described above (e.g. polystyrene / polyethylene-polybutylene block copolymer). Preferably, the block copolymer can be a styrene / butadiene block copolymer, styrene / ethylene-butylene block copolymer, styrene / propylene block copolymer, styrene / butylene-propylene block copolymer or styrene / rubber block copolymer. The glass transition temperature T _{g (h} ar _t) of the hard block of a present invention preferred block copolymer should, in particular at about 100 ° C (e.g., polystyrene block.) And the glass transition temperature T _{g (W} calibration) of the soft block of the present invention preferred block copolymer in particular at about - 55 ° C (e.g. rubber soft block such as polyethylene-butylene soft block).

It is also possible to use block copolymers with multi-arm blocks, so-called "stem block copolymers".

The surfactant (surface-active substance) used in the process according to the invention for formulating the miniemulsion can be an ionic or nonionic surfactant. If a cationic surfactant is used in the process according to the invention, this can be selected from the group of quaternary ammonium compounds such as dimethyldistearylammonium chloride (CTMA-CI); Ester quats, in particular quaternized fatty acid trialkanolamine ester salts; Salts of long-chain primary amines quaternary ammonium compounds such as hexadecyltrimethylammonium chloride; Cetrimonium chloride or lauryldimethylbenzylammonium chloride.

However, if an anionic surfactant is used, this can be selected from the group of soaps; alkylbenzenesulfonates; alkane; olefin; alkyl ether; Glycerinethersulfonaten; α-methyl ester sulfonates; sulfofatty; alkyl sulfates; fatty alcohol; Glycerol ether sulfates; Fettsäureethersulfaten; hydroxy mixed; Monoglyceride (ether) sulfates; Fatty acid amide (ether) sulfates; Mono- and dialkyl sulfosuccinates; Mono- and dialkyl sulfosuccinamates; sulfotriglycerides; amide soaps; Ether carboxylic acids and their salts; Fettsäureisothionaten; Fettsäuresarcosinaten; Fatty acid taurides; N-acylamino acids such as acyl lactylates, acyl tartrates, acyl glutamates and acyl aspartates; oligoglucoside sulfates; Protein fatty acid condensates, in particular vegetable products based on wheat; Alkyl (ether) phosphates.

When nonionic surfactants are used in the process according to the invention, this surfactant can be selected from the group of (i) non-polymeric nonionic surfactants such as alkoxylated, preferably ethoxylated fatty alcohols, alkylphenols, fatty amines and fatty acid amides; alkoxylated triglycerides, mixed ethers and mixed formals; optionally partially oxidized alk (en) yl oligoglycosides; Glucoronsäurederivaten; Fatty acid N-alkyl glucamides; Protein hydrolyzates, in particular alkyl-modified protein hydrolyzates; low molecular weight chitosan compounds; Zuckerestern; sorbitan; Amine oxides; and (ii) polymeric nonionic surfactants such as fatty alcohol polyglycol ethers; alkylphenol polyglycol; Fettsäurepolyglykolestem; Fatty acid amide polyglycol ethers; Fettaminpolyglykolethem; Polyolfettsäureestem; Polysorbates. In general, the gel capsules obtainable by the process according to the invention have an active substance and / or active substance (s) content of 95% by weight to 0.1% by weight. The content of the block copolymer (s) is preferably in the range from 5% by weight to 95% by weight. The content of carrier oil phase which may be present can be up to about 95% by weight. If a highly active ingredient is used in small concentrations, the rest is filled up with carrier oil. Reference can be made to the above explanations.

The present invention also relates to the gel capsules which can be produced by the process according to the invention and are loaded with active substances in the form of active substance-containing matrix or depot systems.

The gel capsules produced by the process according to the invention and loaded with active and / or active substance (s) in the form of active and / or active substance-containing matrix or depot systems preferably contain at least one active or active substance-containing oil phase in a gel matrix based on at least one block copolymer. The active and / or active substance itself can represent the oil phase or can be dissolved in a carrier oil. In the latter case, the carrier oil phase can be selected from the group of paraffin oils, isoparaffin oils, silicone oils, glycerides, triglycerides, naphthalene-containing oils, hydrocarbon-containing solvents and mixtures thereof.

The ratio between the active or active ingredient used in the gel capsule and the carrier oil optionally used can vary within wide limits. A quantity-based or weight-based ratio of active and / or active ingredient to carrier oil of 1: 99 to 99: 1 is possible.

The gel matrix can be formed in the gel capsules according to the invention due to physical interactions, in particular physical network formation, between the active or active substance-containing oil phase on the one hand and the at least one block copolymer on the other hand. The gel capsules according to the invention loaded with active substances generally have a particle size of approximately 10 nm to approximately 600 nm, in particular approximately 20 nm to approximately 500 nm.

The gel capsules of oil phase and block copolymer according to the invention form a particulate, "sponge-like" structure of oil phase and block copolymer. In this structure, the oil phase and the block copolymer can be present in a homogeneous distribution. However, the block copolymers are preferably in associated form and the oil phase is distributed therein or above.

The gel capsules according to the invention loaded with active substances contain a particularly oil-soluble, preferably hydrophobic active substance. This active ingredient can in particular be selected from the group of fragrances, fragrance mixtures, fragrance preparations; oils such as essential oils, perfume oils, care oils and silicone oils; Antioxidants and biologically active substances; oil-soluble vitamins and vitamin complexes; Enzymes and enzymatic systems; cosmetically active substances; substances active in washing and cleaning; Proteins and lipids; Waxing and fats; Foam inhibitors; Graying inhibitors and color protection agents; Soil repellent active ingredients; Bleach activators and optical brighteners; amines; Dyes, color pigments and / or coloring substances; and mixtures of the compounds listed above.

The active ingredient contained in the gel capsules according to the invention can be essentially water-insoluble or at least only sparingly soluble in the aqueous phase. In general, the active ingredient is then less than 10%, preferably less than 5%, in particular less than 1%, soluble in the aqueous phase.

The gel capsules according to the invention generally have an active substance and / or active substance (s) content of 95% by weight to 0.1% by weight. The block copolymer (s) content can be 5% by weight to 95% by weight. If a carrier oil phase is present, its content can be up to about 95% by weight. All of the above weight data are based on the gel capsules. If a highly active ingredient is used in small concentrations, the rest is filled up with carrier oil. Reference can be made to the above explanations.

With regard to the chemical nature of the block copolymer, reference can be made to the above statements.

The present invention also relates to the uses of the gel capsules according to the invention.

The possible uses of the active or active ingredient-containing gel capsules produced by the process according to the invention are very numerous and extensive.

Thus, the gel capsules that can be produced by the processes according to the invention can be used as delivery systems, in particular in the field of cosmetics and personal care (e.g. for deodorants, hair treatment agents, shampoos, shower and washing gels etc.), in the field of pharmacy, in the Adhesive processing and / or in the area of detergents and cleaning agents (e.g. in dishwashing detergents, fabric softeners, detergents for washing at different temperatures, etc.).

In particular, the active or active substance-containing gel capsules produced by the processes according to the invention can be used as delivery systems for the controlled release of active substances or active substances. The active substances are released by the selection and / or amount of the composition of the gel capsules. According to the invention, the term composition here means in particular the type and / or amount of the block copolymer or the type and / or amount of the active and / or active substance-containing oil phase.

The release of the active substances can be controlled in particular by controlling the glass transition temperatures of the polymer blocks of the block copolymer and thus via the gel softening temperature of the gel capsules. The gel capsules according to the invention can be used in particular as delivery systems in which the active ingredient is released over a longer period of time by prolonged or delayed release ("sustained-release effect"). The active ingredient is released in particular without the influence of external forces.

The present invention also relates to cosmetics, personal care products, pharmaceuticals, adhesives or detergents and cleaning agents which contain the gel capsule according to the invention in the form of an active or active ingredient-containing matrix or. Depot systems included.

In particular, the gel capsules obtainable by the process according to the invention, loaded with active and / or active substance (s), in or on objects, such as preferably cosmetic or scented towels (e.g. for use in laundry dryers), scent strips or cards made of cardboard, Cardboard or paper and the like can be used.

The present invention shows a number of advantages over the prior art.

In the method described according to the invention, the gel structure is formed on the basis of physical interactions. Therefore, no polymerization steps are necessary for the encapsulation, as is the case in the process known from the prior art. Polymerizations, which take place in particular with the formation of free radicals, often lead to the decomposition of the active and / or active ingredient. The invention thus provides an encapsulation method which is also suitable for sensitive active substances and / or active substances.

In addition, the method according to the invention has the advantage that it can be used for almost any particular hydrophobic active and / or active ingredient. The quantitative ratio of active and / or active ingredient (s) to any oil carrier phase used can be varied within a wide range. simultaneously an almost monodisperse capsule size distribution is achieved by the miniemulsion process.

The gel capsules provided by the process according to the invention are smaller and more uniform particles than those obtained by processes according to the prior art (dropletization, spray drying or polymerization processes).

The gel capsules obtainable by the process according to the invention have an extremely high encapsulation efficiency. In general, active ingredients and / or active ingredients can be encapsulated up to a content of 95%. The open-pore gel capsule system allows a uniform and slow fragrance release that can be controlled by suitable compositions of the gel capsules.

In contrast to active ingredients and / or active ingredients encapsulated in waxes or triglycerides, the gel capsules according to the invention contain significantly fewer residues. Since these gel capsules do not have any annoying, insoluble capsule shells, they can be easily processed into numerous interesting products. The numerous possible uses of the gel capsules according to the invention are also due to the wide variation in the hardness of the gel capsules.

Further refinements, modifications and variations as well as advantages of the present invention are readily recognizable and realizable for the person skilled in the art upon reading the description, without thereby leaving the scope of the present invention.

The present invention is illustrated by means of the following exemplary embodiments, which, however, in no way limit the invention. WORKING EXAMPLES

Example 1 :

1a) Orange terpene is heated to 88 ° C., mixed with 20% Kraton G-1651 (styrene / rubber block copolymer, from Kraton Polymers) and stirred at 88 ° C. to form a homogeneous mixture. The oil phase (15 g) thus obtained is dispersed into an aqueous phase of 150 g of water and 3 g of SDS (sodium dodecyl sulfate, Sigma) using an Ultra-Turrax stirrer at a temperature of 95 ° C. The resulting crude emulsion is converted into a mini emulsion using a high-pressure homogenizer (5 minutes at a pressure of 1000 bar). The mini emulsion is allowed to cool with stirring. Gelled orange oil gel particles are found which have a particle size in the range of 160 nm and a narrow particle size distribution.

The particle dispersion is applied to a cleaning cloth and develops a pleasant fragrance for a long time. After using the cleaning wipes on a solid substrate (glass pane), the smell is noticeably longer than when using unencapsulated, ungelled scents.

1 b) Under analog test conditions as in Example 1, a gel phase was prepared in a ratio of 20:80 using a mixture of orange terpene and Shellsol T (Idoparaffin, Shell).

The presence of the cleaning-active carrier oil also results in an improved cleaning effect of the wipes for greasy soiling. Example 2:

A 5:95 mixture of rose oil and an inert isoparaffin carrier oil (Isopar M, Exxon) is heated to 84 ° C., mixed with 27% Kraton G-1650 (styrene / rubber block copolymer, from Kraton Polymers) and stirred at 90 ° C to a homogeneous mixture. The oil phase (15 g) is dispersed into an aqueous phase of 150 g of water and 2.7 g of SDS (sodium dodecyl sulfate, Sigma) using an Ultra-Turrax stirrer at a temperature of 90 ° C. The resulting crude emulsion is converted into a mini emulsion using a high-pressure homogenizer (5 minutes at a pressure of 1000 bar). The mini emulsion is allowed to cool with stirring. Gelled rose oil carrier oil particles are found which have a particle size in the range of 180 nm and a narrow particle size distribution. The particle dispersion is stirred into a fabric softener and develops a pleasant fragrance for a long time after using the fabric softener on the laundry. The fragrance is noticeably longer after use than when using unencapsulated, ungelled fragrances.

Example 3:

A 5:95 mixture of vitamin A palmitate and an inert carrier oil (isopropyl palmitate) is heated to 82 ° C., mixed with 24% Versagel C HP (block copolymer, Penreco) and stirred at 80 ° C. to form a homogeneous mixture , The oil phase (15 g) is dispersed into an aqueous phase of 150 g of water and 3 g of DTAB (dodecyltrimethylamommium bromide, Aldrich) using an Ultra-Turrax stirrer at a temperature of 80 ° C. The resulting crude emulsion is converted into a mini emulsion using a high-pressure homogenizer (3 minutes at a pressure of 900 bar). The mini emulsion is allowed to cool with stirring. Gelled vitamin A in carrier oil particles are found which have a particle size in the range of 120 nm and a narrow particle size distribution.

The particle dispersion is stirred into a skin cream and contains the vitamin A palmitate in the product for a long time. The stability during storage is significantly higher than when using the unencapsulated, ungelled vitamin A palmitate.

Claims

claims:

1. A process for the production of gel capsules loaded with active and / or active substance (s) in the form of matrix and / or depot systems containing active and / or active substance, characterized by the following process steps:

(a) providing a mixture of an active and / or active substance-containing oil phase and at least one block copolymer;

(b) providing a water / surfactant mixture;

2. The method according to claim 1, characterized in that in step (a) the mixture of at least one block copolymer and an active and / or active substance-containing oil phase is provided in that the Block copolymer is added with heating of the active and / or active substance-containing oil phase, in particular with stirring, or vice versa, in particular wherein the heating temperature is above the gelation temperature of the resulting dispersion.

3. The method according to claim 1 or 2, characterized in that the active and / or active ingredient itself is the oil phase or is dissolved in a carrier oil, wherein the carrier oil phase can be selected in particular from the group of paraffin oils, isoparaffin oils, silicone oils, glycerides , Trigylcerides, naphthalene-containing oils, hydrocarbon-containing solvents and mixtures thereof.

4. The method according to any one of claims 1 to 3, characterized in that in step (c) the preparation of the dispersion takes place in that the mixture prepared in step (a) from at least one block copolymer and an active and / or active substance-containing oil phase in the water / surfactant mixture prepared according to step (b) is introduced or vice versa.

5. The method according to any one of claims 1 to 4, characterized in that the optionally carried out in step (d) emulsification of the dispersion obtained under (c) is carried out by the action of shear forces.

6. The method according to any one of claims 1 to 5, characterized in that the production of the miniemulsion carried out in step (e) takes place by the action of shear forces, in particular by ultrasound treatment, high-pressure homogenization and / or microfluidizer treatment.

7. The method according to any one of claims 1 to 6, characterized in that the formation of the miniemulsion in step (e) is carried out under a homogenizing pressure of 50 bar to 30,000 bar, in particular 300 bar to 2,500 bar.

8. The method according to any one of claims 1 to 7, characterized in that the cooling in step (f) to solidify the active and / or Active substance-laden oil droplets of the mini emulsion leads to gel capsules loaded with active substances and / or active substances, the mean particle sizes of which correspond to that of the oil phase droplets of the mini emulsion.

9. The method according to any one of claims 1 to 8, characterized in that the gel formation in step (f) takes place due to physical interactions, in particular physical network formation.

10. The method according to any one of claims 1 to 9, characterized in that the mini emulsion is an essentially aqueous emulsion stabilized by the surfactant of the block copolymers and the active and / or active ingredient-containing oil phase, in particular with an average particle size of the emulsified Oil phase droplets from about 10 nm to about 600 nm, in particular from about 20 nm to about 500 nm.

11. The method according to any one of claims 1 to 10, characterized in that the separation optionally carried out in step (g) is carried out by customary methods, in particular by freeze drying (lyophilization), evaporation of the dispersant, ultrafiltration, dialysis or spray drying under gentle conditions.

12. The method according to any one of claims 1 to 11, characterized in that all process steps (a) to (e) are carried out at temperatures above the gelation temperature of the respective mixtures, dispersions and / or emulsions.

13. The method according to any one of claims 1 to 12, characterized in that the active and / or active ingredient is a particularly oil-soluble, preferably hydrophobic active and / or active ingredient, which can in particular be selected from the group of fragrances, fragrance mixtures, fragrance preparations ; oils such as essential oils, perfume oils, care oils and silicone oils; Antioxidants and biologically active substances; oil-soluble vitamins and vitamin complexes; Enzymes and enzymatic systems; cosmetically active substances; substances active in washing and cleaning; Proteins and lipids; Waxing and fats; Foam inhibitors; Graying inhibitors and color protection agents; Soil-repellent active ingredients; Bleach activators and optical brighteners; amines; Dyes, color pigments and / or coloring substances; and mixtures of the aforementioned compounds.

14. The method according to any one of claims 1 to 13, characterized in that the active and / or active ingredient is substantially water-insoluble or at least only sparingly soluble in the aqueous phase, in particular wherein the active and / or active ingredient in the aqueous phase less than 10%, preferably less than 5%, in particular less than 1%, is soluble.

15. The method according to any one of claims 1 to 14, characterized in that in the miniemulsion prepared in step (e) the content of active and / or active ingredient (s) 0.01 wt .-% to 50 wt .-%, preferably 2% by weight to 30% by weight, and / or the content of block copolymer (s) is 0.01% by weight to 50% by weight, preferably 2% by weight to 20% by weight , and / or the content of any carrier oil (s) present is 1% by weight to 50% by weight, preferably 2% by weight to 30% by weight, and / or the water content is 50% by weight up to 99% by weight, preferably 70% by weight to 90% by weight, and / or the content of surfactant (s) is 0.01% by weight to 10% by weight, preferably 0.5% by weight .-% to 5 wt .-%, is, all weights are based on the mini emulsion.

16. The method according to any one of claims 1 to 15, characterized in that the block copolymer is an in particular hydrophobic, with the active and / or active substance-containing oil phase below the corresponding gel formation temperature, a gel, in particular organogel, forming organic copolymer.

17. The method according to any one of claims 1 to 16, characterized in that the block copolymer is a polymer consisting of at least two blocks or components, wherein at least one of the blocks is a hard block and at least one other of the blocks is a soft block.

18. The method according to any one of claims 1 to 17, characterized in that the glass transition temperatures of the hard and the soft block differ by at least 50 ° C, in particular at least 60 ° C, preferably at least 70 ° C.

19. The method according to any one of claims 1 to 18, characterized in that the hard block has a glass transition temperature T _g (hard)> 20 ° C, in particular _g (hard)> 50 ° C, preferably Tg ( _ha rt)> 90 ° C , and / or that the soft block has a glass transition temperature T _g ( _We ich) ≤20 ° C, in particular T _g ( _We i _C h) ≤ 0 ° C, preferably T _g ( _We ich) ≤- 45 ° C ,

20. The method according to any one of claims 1 to 19, characterized in that at least one block of the block copolymer, preferably the hard block, is not or only poorly oil-soluble and that at least one other block of the block copolymer, preferably the soft block, is oil-soluble.

21. The method according to any one of claims 1 to 20, characterized in that at least one block of the block copolymer, preferably the hard block, is less oil-soluble than at least one other block of the block copolymer, preferably the soft block.

22. The method according to any one of claims 1 to 21, characterized in that the hard block of the block copolymer is selected from the group of polystyrenes, poly (meth) acrylates, polycarbonates, polyesters, polyanilines, poly-p-phenylenes, polysulfone ethers, polyacrylonitriles, Polyamides, polyimides, polyethers, polyvinyl chlorides and their mixtures and / or that the soft block of the block copolymer is selected from the group of rubbers, in particular optionally substituted polyalkylenes, preferably polybutadienes, and mixtures of rubbers or polyalkylenes, such as polybutadiene-ethylene, polybutadiene-propylene , Polyethylene ethylene; polyvinyl alcohols; Polyalkylene glycols such as polyethylene glycols and polypropylene glycols; Polydimethoxysiloxanen; Polyurethanes.

23. The method according to any one of claims 1 to 22, characterized in that the block copolymer is a styrene / butadiene block copolymer, styrene / butylene block copolymer, styrene / propylene block copolymer, styrene / butylene-propylene block copolymer or styrene / rubber block copolymer ,

24. The method according to any one of claims 1 to 23, characterized in that the surfactant is an ionic or nonionic surfactant.

25. The method according to claim 24, characterized in that the surfactant is a cationic surfactant, which can in particular be selected from the group of quaternary ammonium compounds such as dimethyldistearylammonium chloride (CTMA-CI); Ester quats, in particular quaternized fatty acid trialkanolamine ester salts; Salts of long chain primary amines, quaternary ammonium compounds such as hexadecyltrimethylammonium chloride; Cetrimonium chloride or lauryldimethylbenzylammonium chloride.

26. The method according to claim 24, characterized in that the surfactant is an anionic surfactant, which can in particular be selected from the group of soaps; alkylbenzenesulfonates; alkane; olefin; alkyl ether; Glycerinethersulfonaten; α-methyl ester sulfonates; sulfofatty; alkyl sulfates; fatty alcohol; glycerol ether; Fettsäureethersulfaten; hydroxy mixed; Monoglyceride (ether) sulfates; Fatty acid amide (ether) sulfates; Mono- and dialkyl sulfosuccinates; Mono- and dialkyl sulfosuccinamates; sulfotriglycerides; amide soaps; Ether carboxylic acids and their salts; Fettsäureisothionaten; Fatty acid sarcosinates; fatty acid taurides; N-acylamino acids such as acyl lactylates, acyl tartrates, acyl glutamates and acyl aspartates; oligoglucoside sulfates; Protein fatty acid condensates, in particular vegetable products based on wheat; Alkyl (ether) phosphates.

27. The method according to claim 24, characterized in that the surfactant is a nonionic surfactant, which can be selected from the group of (i) non-polymeric nonionic surfactants such as alkoxylated, preferably ethoxylated fatty alcohols, alkylphenols, fatty amines and fatty acid amides; alkoxylated triglycerides, mixed ethers and mixed formals; optionally partially oxidized alk (en) yl oligoglycosides; Glucoronsäurederivaten; Fatty acid N-alkyl glucamides; Protein hydrolyzates, in particular alkyl-modified protein hydrolyzates; low molecular weight chitosan compounds; Zuckerestern; sorbitan; Amine oxides; and (ii) polymeric nonionic surfactants such as fatty alcohol polyglycol ethers; Alkylphenolpolyglykolethem; fatty acid polyglycol esters; Fettsäureamidpolyglykolethern; Fatty amine polyglycol ethers; polyol fatty acid esters; Polysorbates.

28. The method according to any one of claims 1 to 27, characterized in that in the gel capsules obtained in step (f) and optionally (g) the content of active and / or active ingredient (s) 95 wt .-% to 0.1 % By weight and / or the content of block copolymer (s) is 5% by weight to 95% by weight and / or the content of any carrier oil phase which may be present is up to approximately 95% by weight, all the weight data being based on the gel capsules are covered.

29. Gel capsules loaded with active and / or active substance (s) in the form of active and / or active substance-containing matrix and / or depot systems, obtainable by the process according to claims 1 to 28.

30. Gel capsules loaded with active and / or active substance (s) in the form of active and / or active substance-containing matrix and / or depot systems containing at least one active and / or active substance-containing oil phase in a gel matrix based on at least one block copolymer, in particular wherein the active and / or active ingredient itself is the oil phase or is dissolved in a carrier oil, in particular where the carrier oil phase can be selected from the group of paraffin oils, isoparaffin oils, silicone oils, glycerides, triglycerides, naphthalene-containing oils, hydrocarbon-containing solvents and mixtures thereof.

31. Gel capsules according to claim 30, characterized in that the formation of the gel matrix due to physical interactions, in particular physical network formation, between the active and / or active ingredient-containing Oil phase on the one hand and the at least one block copolymer on the other hand.

32. Gel capsules according to claim 30 or 31, characterized in that they have a particle size of approximately 10 nm to approximately 600 nm, in particular approximately 20 nm to approximately 500 nm.

33. Gel capsules according to one of claims 30 to 32, characterized in that they are in the form of particulate, in particular sponge-like structures of oil phase and block copolymer, in particular where oil phase and block copolymer are in homogeneous distribution or in particular where the block copolymers are in associated form

34. Gel capsules according to any one of claims 30 to 33, characterized in that the active and / or active ingredient is a particularly oil-soluble, preferably hydrophobic active and / or active ingredient, which can in particular be selected from the group of fragrances, fragrance mixtures, fragrance preparations ; Oils such as essential oils, perfume oils, care oils and silicone oils; Antioxidants and biologically active substances; oil-soluble vitamins and vitamin complexes; Enzymes and enzymatic systems; cosmetically active substances; substances active in washing and cleaning; Proteins and lipids; Waxing and fats; Foam inhibitors; Graying inhibitors and color protection agents; Soil-repellent active ingredients; Bleach activators and optical brighteners; amines; Dyes, color pigments and / or coloring substances; and mixtures of the compounds listed above.

35. Gel capsules according to any one of claims 30 to 34, characterized in that the active and / or active ingredient is substantially water-insoluble or at least only sparingly soluble in the aqueous phase, in particular wherein the active and / or active ingredient in the aqueous phase is less than 10%, preferably less than 5%, in particular less than 1%, is soluble.

36. Gel capsules according to one of claims 30 to 35, characterized in that the content of active and / or active ingredient (s) in the gel capsules is 95% by weight to 0.1% by weight and / or the content of Block copolymer (s) is 5% by weight to 95% by weight and / or the content of any carrier oil phase which may be present is up to about 95% by weight, all the weights given being based on the gel capsules.

37. Gel capsules according to any one of claims 30 to 36, characterized in that the block copolymer is an in particular hydrophobic, with the active and / or active substance-containing oil phase under the corresponding gel formation temperature, a gel, in particular organogel, forming organic copolymer.

38. Gel capsules according to one of claims 30 to 37, characterized in that the block copolymer is a polymer consisting of at least two blocks or components, at least one of which is a hard block and at least one other is a soft block, in particular where the glass transition temperatures of the hard and soft block by at least 50 ° C, in particular at least 60 ° C, preferably at least 70 ° C, different and / or particularly wherein the hard block has a glass transition temperature Tg (hard)> 20 ° C, particularly Tg (h _ar t) > 50 ° C, preferably Tg _(ha r _t)> 90 ° C, and / or the soft block has a glass transition temperature T _g _(We ic) ≤ 20 ° C, in particular T _g _(WE i) ≤ 0 ° C, preferably from T _g _(W calibration) ≤-45 ° C, comprising.

39. Gel capsules according to one of claims 30 to 38, characterized in that at least one of the blocks of the block copolymer, preferably the hard block, is not or only poorly oil-soluble and at least one other block of the block copolymer, preferably the soft block, is oil-soluble.

40. Gel capsules according to one of claims 30 to 39, characterized in that at least one block of the block copolymer, preferably the hard block, is less oil-soluble than at least one other block of the block copolymer, preferably the soft block.

41. Gel capsules according to one of claims 30 to 40, characterized in that the hard block of the block copolymer can be selected from the group of polystyrenes, poly (meth) acrylates, polycarbonates, polyesters, polyanilines, poly-p-phenylenes, polysulfone ethers, polyacrylonitriles , Polyamides, polyimides, polyethers, polyvinyl chlorides and their mixtures and / or that the soft block of the block copolymer can be selected from the group of rubbers, in particular optionally substituted polyalkylenes, preferably polybutadienes, and mixtures of rubbers or polyalkylenes, such as polybutadiene-ethylene, polybutadiene -Propylene, polyethylene ethylene; polyvinyl alcohols; Polyalkylene glycols, such as polyethylene glycols, polypropylene glycols; Polydimethoxysiloxanen; polyurethanes; in particular wherein the block copolymer is a styrene / butadiene block copolymer, styrene / ethylene-butylene block copolymer, styrene / propylene block copolymer, styrene / butylene-propylene block copolymer or styrene / rubber block copolymer.

42. Use of the gel capsules according to claims 29 to 41 as delivery systems, in particular in the field of cosmetics and personal care, in the field of pharmacy, in adhesive processing and / or in the area of detergents and cleaning agents.

43. Use of the gel capsules according to claims 29 to 41 for the controlled release of active and / or active substances.

44. Use according to claim 42 or 43, characterized in that the control of the release by selecting the type and / or amount of the composition of the gel capsules, in particular by selecting the type and / or amount of the block copolymer and / or by selecting the The type and / or amount of the active and / or active substance-containing oil phase takes place.

45. Use according to claims 42 to 44, characterized in that the control of the release of the active and / or active ingredients via the control of the glass transition temperature of the polymer blocks Block copolymer and / or via the gel softening temperature of the gel capsules.

46. Use of the gel capsules according to claims 29 to 41 as delivery systems, in particular with prolonged or delayed release of the active ingredient and / or active ingredient (sustained-release effect).

47. Compositions, in particular washing and cleaning agents, cosmetics, personal care products or adhesives, containing gel capsules according to claims 29 to 41.

48. Objects containing gel capsules according to claims 29 to 41, for example cosmetic or scented towels (eg for use in tumble dryers), scent strips or cards made of cardboard, cardboard or paper and the like.