DE102013000586A1 - Active substance-containing nanoparticles useful e.g. for topical application on pharyngeal mucosa, comprise carrier or matrix material, dispersant, first active substance, and second active substance comprising acidic glycosaminoglycan - Google Patents

Abstract

Active substance-containing nanoparticles comprise at least one carrier- and/or matrix material, at least one dispersant, at least one topically applicable first active substance which is embedded and/or incorporated in the carrier- and/or matrix material, and at least one second active substance comprising acidic glycosaminoglycan or its derivatives or salts. Independent claims are also included for: (1) a dispersion comprising the above active substance-containing nanoparticles; (2) a dosage- and/or application form present in solid-, liquid-, paste- or aerosol-like form, comprising the active substance-containing nanoparticles; and (3) a dosage- and/or application form present in liquid-, paste- or aerosol-like form, comprising the dispersion. ACTIVITY : Antiinflammatory; Virucide. No biological data given. MECHANISM OF ACTION : None given.

Description

The present invention relates to the field of treatment of the oral or pharyngeal mucosa or the oral cavity and in particular the field of dental prophylaxis or therapy or the field of treatment of hoarseness and / or inflammatory diseases of the oropharynx, preferably colds or influenza infections.

In particular, the present invention relates to active ingredient-containing nanoparticles which are suitable for topical application on the oral or pharyngeal mucosa or in the oral cavity.

Furthermore, the present invention relates to the use of nanoparticles for prophylactic or curative treatment of the oral or pharyngeal mucosa or the oral cavity.

Another object of the present invention is a process for the preparation of active ingredient-containing nanoparticles, which are suitable for topical application to the oral or pharyngeal mucosa or in the oral cavity.

In addition, the present invention relates to a dispersion which contains active ingredient-containing nanoparticles and is suitable for topical application to the oral or pharyngeal mucosa or the oral cavity. In addition, the present invention also relates to the uses of such dispersions.

Finally, the invention relates to dosage forms or application forms which contain active ingredient-containing nanoparticles according to the present invention.

A curative or prophylactic treatment of the oral or pharyngeal mucosa or the oral cavity can be made or indicated for many reasons, especially in hoarseness and / or inflammatory diseases of the mouth and throat, preferably colds or influenza infections. Similarly, it may be provided to perform a curative or prophylactic treatment of the oral or pharyngeal mucosa in the context of a dental prophylaxis or therapy for improving oral hygiene in general.

In general, the curative or prophylactic treatment of the oral or pharyngeal mucosa or the oral cavity pasty or viscous dosage forms, such as creams or pastes, liquid application forms, such as mouthwashes or rinse solutions, and solid dosage forms, such as lozenges or capsules, but also aerosol-like Application forms, especially oral sprays used.

Treatments of the oral cavity in the context of general oral hygiene and / or dental prophylaxis usually pursue the aim of preventing the development of diseases on the teeth and the periodontium and in the case of existing diseases, to heal or mitigate. This is generally done by periodically and thoroughly removing food debris and plaque to prevent tooth decay and various periodontal diseases such as periodontal disease. In addition, one of the goals of oral hygiene is to create a fresh breath or a long-lasting sensation of freshness in the mouth and to prevent halitosis. Furthermore, it is desirable in the context of oral care to prevent the symptom of dry mouth, as it often occurs in smokers. Usually oral cavity treatments are carried out by daily brushing the teeth with toothbrush and toothpaste. In addition, complementary measures, such as mouthwashes, mouthwashes or mouth sprays, lozenges or the like may be used, especially if there is no possibility for brushing teeth after taking a meal. Oral hygiene products may include antimicrobials for the inhibition of plaque, such as chlorhexidine or triclosan, as well as flavoring agents intended to provide fresh breath.

In the relief of hoarseness and / or inflammatory diseases of the oropharynx, which are particularly associated with colds or flu-like infections, is especially the reassurance or cure of an irritated oral and pharyngeal mucosa, the alleviation of pain symptoms and a disinfectant Effect in the foreground. Usually, mouthwashes, mouthwashes, mouthwashes, mouthwashes, lozenges or creams are also used for this purpose, which contain antimicrobial, antiinflammatory, analgesic and wound healing promoting agents can. In addition, the compositions often contain flavors or aromas, which should leave the user a pleasant sensation of freshness in the mouth.

However, many of the products used in the prior art for the treatment of the oral or pharyngeal mucosa or the oral cavity, in particular in connection with the oral hygiene or the treatment of hoarseness and / or inflammatory diseases of the oropharynx are in relation to their Effect and application properties are not always optimal.

Frequently, the measures known in the prior art have the problem of a too short duration of action and effective intensity of the ingredients, so that even a short time after the treatment or use, the effect undesirably wears off. The reason is that the liability and / or the whereabouts, for example by adsorption, of the active ingredients used in the oral or pharyngeal mucosa - and thus the concentration at the site of action to ensure adequate efficacy - often insufficient, namely, a satisfactory duration of action is detrimental because the active ingredients used can not reach their full effectiveness at the site of action. Especially in the case of liquid administration or application forms, such as mouthwash solutions, the effect of short duration of action is even more pronounced since such dosage forms are spat out or swallowed down by the users or patients after a short reaction time. But even the effect of in solid dosage forms, especially lozenges, applied ingredients usually decreases quickly, since sometimes the dissolved components are swallowed too fast and thus no adequate adsorption of the active ingredients is guaranteed to the oral or pharyngeal mucosa.

In addition, with the measures known in the prior art for the treatment of the oral or pharyngeal mucosa or the oral cavity, there is often no long-lasting sensation of freshness, in particular for avoiding halitosis or bad breath, also for the abovementioned reasons.

Also, based on the aforementioned measures, the above-described symptom of dry mouth, as often occurs in smokers or in connection with hoarseness and influenza infections, can only insufficiently alleviate.

The present invention is therefore based on the object for the oral hygiene or for the treatment of diseases of the oropharynx, especially in the context of topical application to the oral and pharyngeal mucosa or in the oral cavity to provide suitable application forms or oral care products, which at least largely avoid the previously described disadvantages of the prior art or at least mitigate it.

In addition, the present invention has for its object to provide products for the topical treatment of the oral or pharyngeal mucosa or the oral cavity, which cause a long-lasting effect and an enhancement of freshness sensation in the oral cavity. In addition, the symptom of dry mouth should be effectively prevented or alleviated.

To achieve the object described above, the present invention proposes active ingredient-containing nanoparticles according to claim 1; Further advantageous embodiments are the subject of this dependent claims.

Another object of the present invention is also the use of nanoparticles according to the invention according to the relevant claims.

Yet another subject of the present invention is a process for the preparation of active ingredient-containing nanoparticles according to the independent claim hereof; Further advantageous embodiments are the subject of this dependent claims.

In addition, the present invention is a dispersion containing active ingredient-containing nanoparticles, according to the independent claim hereof; Further advantageous embodiments are the subject of this dependent claims.

Yet another object of the present invention are the uses of a dispersion according to the relevant claims.

Finally, the subject of the present invention is a dosage form or administration form which contains active ingredient-containing nanoparticles according to the relevant claims.

It goes without saying that the following special embodiments, embodiments or the like, which are described only in connection with an aspect of the invention, apply mutatis mutandis in relation to the other aspects of the invention without this expressly needs mention.

Furthermore, it must be noted in the context of the present invention that those skilled in the art should select each of the abovementioned relative or percentage, in particular weight-related quantities, that the sum of the respective ingredients, active ingredients, additives or auxiliaries or the like is always 100%. result. This is understood by the skilled person but by itself.

Incidentally, the person skilled in the art may deviate from the number, range or quantity specified below, depending on the application or the individual case, without departing from the scope of the present invention.

In addition, it is true that all the parameter information or the like mentioned below can in principle be determined or determined using standardized or explicitly stated determination methods or else determination methods familiar to the person skilled in the art.

• – wobei die Nanopartikel mindestens ein Träger- und/oder Matrixmaterial einerseits sowie mindestens ein Dispergiermittel andererseits aufweisen und
• – wobei die Nanopartikel
• (a) mindestens einen vorzugsweise in das Träger- und/oder Matrixmaterial eingelagerten und/oder inkorporierten, insbesondere topisch applizierbaren ersten Wirkstoff sowie
• (b) mindestens einen zweiten Wirkstoff in Form eines vorzugsweise sauren Glykosaminoglykans oder dessen physiologisch verträglichen Derivaten oder Salzen

enthalten.The present invention accordingly provides, according to a first aspect of the invention, active ingredient-containing nanoparticles which are suitable for topical application on the oral or pharyngeal mucosa or in the oral cavity,

• - wherein the nanoparticles have at least one carrier and / or matrix material on the one hand and at least one dispersant on the other hand, and
• - where the nanoparticles
• (A) at least one preferably incorporated in the carrier and / or matrix material and / or incorporated, in particular topically applied first active ingredient and
• (B) at least one second active ingredient in the form of a preferably acidic glycosaminoglycan or its physiologically acceptable derivatives or salts

contain.

The Applicant has surprisingly found that nanoparticles are obtained by the incorporation or incorporation of at least one active substance in a carrier or matrix material using a dispersant and at least one further active ingredient, based on an acid glycosaminoglycan previously described disadvantages of the prior art can be overcome or reduced. In particular, it has been shown in a completely surprising manner in this connection that the use of a preferably acidic glycosaminoglycan or its physiologically tolerated derivatives or salts also effects an enhancement of the action of the first active substance incorporated or incorporated into the carrier or matrix material Indication of the presence of a synergistic effect is to be evaluated.

The term "nanoparticles", as used in the context of the present invention, is to be understood as being very comprehensive and is not restricted exclusively to particles of the order of nanometers, but expressly also encompasses particles with a size in the μm range. The size specifications or the order of magnitude of the nanoparticles according to the invention preferably relate to an assumed spherical shape. If the nanoparticles deviate from a spherical structure or spherical shape, the size specifications or orders of magnitude may likewise relate to an assumed spherical shape which has an identical volume to the underlying particles and / or particles deviating from the spherical shape. This can be done in particular Rawle, A., "Basic Principles of Particle Size Analysis" Surface Coatings International, Part A, Issue 2003/02 , to get expelled.

The preferred acidic glycosaminoglycans used in the present invention are generally linear mucopolysaccharides formed from repeating saccharides. In general, the saccharide units consist of a uronic acid, in particular glucuronic acid, but also iduronic acid or uronic acid, which are 1,3-glycosidically linked to an amino sugar, such as N-acetylglucosamine. The saccharide units for forming the chain as such, in turn, are linked together 1,4-glycosidically. In particular, it may also be provided that the glycosaminoglycans are further esterified with sulfuric acid or acetic acid. The glycosaminoglycans in question are often in association with biological macromolecules and, for example, can be covalently bound to proteins in large numbers. In this way, they can the framework of many fiber-forming substances, such. As fibrillin, form in the body. A fiction-relevant advantage or a property of the glycosaminoglycans relevant to the invention lies in particular in their ability to absorb water in large quantities while forming a matrix. This is on the one hand with regard to the incorporation of the active ingredients and on the other hand on a moisturization in the skin or mucous membrane in topical application in the mouth or in the oral cavity of importance. Furthermore, the use of acidic glycosaminoglycans leads to a mechanical stabilization of the nanoparticles according to the invention.

In particular, the Applicant has surprisingly found in the context of the present invention, as mentioned above, that in particular the use of a preferably acidic glycosaminoglycan or its physiologically acceptable derivatives or salts, the effect of the first active substance incorporated or incorporated into the carrier or matrix material can significantly increase, so that it can be assumed that a synergistic effect between the preferably acid glycosaminoglycan and the active ingredients used in the invention.

The present invention has numerous other advantages and particularities which distinguish it from the prior art and which are described in detail below:
The active ingredient-containing nanoparticles according to the invention can, especially when applied topically to the oral or pharyngeal mucosa or in the oral cavity, a variety of different, suitable for the treatment of the oral cavity active ingredients, such as antibacterial agents, essential oils or the like, targeted and beyond also time-delayed or release controlled, whereby a very long-lasting effect is achieved. In this context, it has surprisingly been found that the release, in particular the rate of release, also controlled by the particle size of the nanoparticles, the amounts of carrier or matrix material and dispersants used and beyond the amount of preferably acidic glycosaminoglycan targeted and tailor made can be provided so that in total according to the invention active ingredient-containing nanoparticles are provided, which also have a conrolled-release effect with respect to the underlying active substances.

The efficiency of action is also improved as such, since the active substance-containing nanoparticles ensure optimal presence of the active ingredients at the site of action, this - without wishing to be limited to this theory - especially based on a so-called "patchy effect" associated with the application of the nanoparticles of the invention can be explained. Because of their special structure, which will be explained in more detail below, the nanoparticles can form a surface-covering film after their application in the oral cavity, which also reduces transepidermal water loss, which in turn leads to a reduced viscosity of the skin. The increased mobility of the lipids in the skin permits lateral diffusion of the active ingredients through the skin, in particular the oral and pharyngeal mucosa. In addition, the active substance-containing nanoparticles adhere very well to the negatively charged oral mucosa due to their slightly cationic charge, which further improves the transport of the active ingredients to the sites of action or the adsorption on the oral mucosa. In addition, the "patchy effect" causes, in particular, that the nanoparticles can wet a large surface area of up to 50 m ² / g of the oral cavity.

The use of the active ingredient-containing nanoparticles according to the invention thus overall leads to an improvement in the effectiveness and duration of action of the incorporated active substances or ingredients, which goes far beyond the efficiency of action or duration of action achieved with products of the prior art. In particular, the sensation of freshness in the oral cavity can be significantly prolonged by the use of the active ingredient-containing nanoparticles according to the invention.

In addition, the active ingredient-containing nanoparticles according to the invention have a high physical stability, even under the action of shear forces. As the studies conducted by the applicant have surprisingly shown, the mechanical stabilization of the nanoparticles is additionally enhanced by the additional use of at least one preferably acidic glycosaminoglycan or its physiologically compatible derivatives or salts, in particular hyaluronic acid. This could - without wishing to be limited to this theory - result from an additional matrix formation of the glycosaminoglycan, which leads to an amplification of the structures underlying the nanoparticles. Advantageously, at least substantially no escape of active ingredients from the particles occurs under the effect of high shear forces in the case of the nanoparticles according to the invention, as is however the case in conventional liposomes of the prior art. Shear forces cause at most the nanoparticles according to the invention a division of a single particle into two or more particles, wherein the structure of the particles as such, however, remains unchanged, ie the active ingredients are still incorporated or incorporated in the carrier or matrix material. Only the particle size is reduced by the division, which, however, does not adversely affect the effectiveness of the nanoparticles.

In addition, the topical application of the active ingredient-containing nanoparticles according to the invention can also effectively treat or prevent the symptom of dry mouth, which is associated in particular with the use of the at least one acidic glycosaminoglycan and the "patching effect" of the nanoparticles according to the invention.

In addition, the active ingredient-containing nanoparticles according to the present invention can be used extremely versatile. Among other things, the use in toothpaste for the targeted release of flavors and antibacterial agents, especially against the background of the prophylaxis of caries and dental plaque, be provided. In addition, mouthwashes both for dental use and for the relief of hoarseness or colds can be improved in terms of their effect by the incorporation of the active ingredients in the nanoparticles of the invention. Likewise, the use in special applications, such as smoker oral sprays against dry oral mucosa, possible. It can also be provided to use the active ingredient-containing nanoparticles according to the invention as a concentrate for oral sprays. Finally, it is also possible to introduce the nanoparticles according to the invention into solid administration forms, such as lozenges, in particular for the treatment of hoarseness or colds.

Furthermore, in connection with the advantages and special features described above, reference is made at this point to the exemplary embodiments and efficacy studies carried out by the Applicant, which demonstrate the aforementioned effects in an impressive manner and are described in detail below.

The active ingredient-containing nanoparticles according to the invention can be designed in a variety of ways. Preferred embodiments are described below for better understanding:
The nanoparticles according to the invention are distinguished in particular by their very specific physical or physical design, in particular with regard to the presence of a special membrane system according to a particularly preferred embodiment of the present invention.

For in this connection it is particularly preferred if the nanoparticles according to the invention have at least one membrane system. In this case, the membrane system may have at least one membrane or membrane structure.

As far as the membrane system, in particular the membrane or membrane structure of the nanoparticles according to the invention is concerned, this may generally be in contact with the carrier or matrix material of the nanoparticles. In this regard, the membrane system, particularly the membrane and / or membrane structure, can effectively form an interfacial layer with respect to the carrier or matrix material or attach to interfaces of the carrier or matrix material in the form of the underlying membrane, both in a sense as an internal structure in the carrier or matrix material as such ("inner compartmentalization") as well as in the form of an external structure on the outside or surface of the carrier or matrix material ("casing").

In this context, it is thus preferred according to the invention if the membrane system, in particular the membrane or membrane structure, at least partially, preferably at least substantially completely surrounds or envelops the carrier or matrix material.

In addition, with regard to the embodiment of the nanoparticles according to the invention, it is likewise preferred if the membrane system, in particular the membrane or membrane structure, at least partially passes through the carrier or matrix material or is at least partially incorporated into the carrier or matrix material.

Thus, as far as the physical configuration of the nanoparticles is concerned, it can be provided in particular that the nanoparticles, in particular the carrier and / or matrix material, are delimited or compartmentalized by the membrane system, in particular the membrane or membrane structure.

In other words, the membrane or the membrane structure surrounds or traverses the carrier and / or matrix material, which on the one hand results in the formation of an outer interface or shell and on the other hand, and independently thereof, into an inner compartmentalization of the nanoparticles, for example, in the form of a lamellar structure in the interior of the nanoparticles, in particular wherein the carrier and / or matrix material is interrupted by membranes of the dispersant.

The presence of a membrane system leads to an improved mechanical stabilization of the nanoparticles as such, in particular also under the action of shear forces, and furthermore to a further improved controlled release of the active compounds, which also leads to an improved efficacy or prolonged duration of action during application and / or application the nanoparticles in the mouth or in the oral cavity leads. The inventive design of the nanoparticles with the presence of a membrane or membrane structure causes a nationwide deposition and adsorption of active ingredient-containing nanoparticles to the oral mucosa, so that as a result, an excellent penetration of the active ingredients can be achieved at the sites of action.

According to the invention, the membrane system, in particular the membrane and / or membrane structure, at least partially, preferably at least substantially completely, be formed by the dispersant. In this connection, the membrane system, in particular the membrane and / or membrane structure, may be formed as a monomolecular layer or as a bimolecular layer, preferably as a monomolecular layer. In particular, the membrane system can be in the form of a liquid-crystalline system, in particular based on the dispersant. In addition, it can equally be provided that the membrane system is based on a liquid-crystalline mixing system of dispersant and carrier or matrix material in the region of the interface or layer.

In particular, the membrane structure can, as it were, be formed on the basis of interfaces between dispersant on the one hand and matrix material on the other hand or form these interfaces themselves.

In summary, the membrane system can thus form in particular in the manner of an interface within the carrier or matrix material, so that the matrix material is compartmentalized by the dispersant or the membranes. Equally, the membrane system can to some extent form on the surface of the nanoparticles, so that the nanoparticles are partially or completely enveloped by the membrane system based on the dispersant and thus delineate the surrounding medium, such as water or air, of the nanoparticles.

Due to the presence of the membrane system in the interior and / or on the surface of the nanoparticles both an excellent interaction, in particular adhesion or adhesion, of the nanoparticles on the slightly negatively charged oral mucosa and an improved loading of the nanoparticles with the active substances or incorporation of the active ingredients in ensures the nanoparticles.

In summary, the membranes or the membrane structure or the membrane system of the nanoparticles according to the invention thus arise in particular by the inventive combination of the dispersant on the one hand and the carrier or matrix material on the other hand.

Basically, in this context, all pharmaceutically acceptable or food approved carrier or matrix materials on the one hand and dispersants, in particular emulsifiers, on the other hand can be used.

• (i) kationischen Tensiden, insbesondere quartären Ammoniumverbindungen, vorzugsweise Alkyltrimethylammoniumsalzen, bevorzugt Cetrimoniumbromid (Cetyltrimethylammoniumbromid), Dialkyldimethylammoniumsalzen oder Benzalkoniumsalzen, insbesondere Cetylpyridiniumchlorid;
• (ii) anionischen Tensiden, insbesondere Alkylbenzolsulfonaten oder Fettalkoholsulfaten;
• (iii) nichtionischen Tensiden, insbesondere Polyalkylenglykolethern, vorzugsweise Ethern auf Basis von Polyethylenglykolen und Fettalkoholen, Alkylglucosiden, Alkylpolyglucosiden oder Nonylphenolethoxylaten;
• (iv) amphoteren Tensiden, insbesondere Betainen, vorzugsweise Cocamidopropylbetain, oder Sultainen; und
• (v) deren Mischungen und Kombinationen

ausgewählt sein.It has proved to be particularly advantageous in the context of the present invention if the dispersant is selected from surfactants or amphiphilic substances or surfactants. In particular, the dispersant can be selected from the group of

• (i) cationic surfactants, in particular quaternary ammonium compounds, preferably alkyltrimethylammonium salts, preferably cetrimonium bromide (cetyltrimethylammonium bromide), dialkyldimethylammonium salts or benzalkonium salts, in particular cetylpyridinium chloride;
• (ii) anionic surfactants, especially alkylbenzenesulfonates or fatty alcohol sulfates;
• (iii) nonionic surfactants, in particular polyalkylene glycol ethers, preferably ethers based on polyethylene glycols and fatty alcohols, alkyl glucosides, alkyl polyglucosides or nonylphenol ethoxylates;
• (iv) amphoteric surfactants, especially betaines, preferably cocamidopropylbetaine, or sultaines; and
• (v) their mixtures and combinations

be selected.

The choice of a suitable emulsifier is within the ordinary skill of the art, and the skilled artisan is always able to select the emulsifier or the dispersant against the background of his expertise so that the nanoparticles receive the desired properties.

In addition, it can be provided that the dispersant of surface-active substances, in particular natural and / or nature-identical surfactants and / or surfactants of natural origin, preferably from the group of physiological bile acids, in particular sodium cholate, sodium dehydrocholate, sodium deoxycholate or sodium taurocholate; Phospholipids, in particular lecithins; and their mixtures and combinations are selected.

As far as the amount of dispersant used is concerned, it can vary within wide limits. With regard to the properties of the nanoparticles according to the invention, it has proved to be advantageous if the nanoparticles contain the dispersant in an amount in the range from 0.1 to 20% by weight, in particular in the range from 0.5 to 15% by weight, preferably in the range from 1 to 10% by weight, preferably in the range from 2 to 8% by weight, based on the nanoparticles.

• (i) Glyceriden und/oder Glycerinestern, insbesondere Di- oder Triglyceriden und/oder Glycerindi- oder Glycerintriestern, vorzugsweise Di- oder Triglyceriden und/oder Glycerindi- oder Glycerintriestern geradkettiger gesättigter Fettsäuren mit 8 bis 30 Kohlenstoffatomen, bevorzugt Di- oder Triglyceriden und/oder Glycerindi- oder Glycerintriestern von Caprylsäure, Caprinsäure, Undecansäure, Laurinsäure, Palmitinsäure, Stearinsäure und/oder Arachinsäure;
• (ii) Fettalkoholen oder deren Estern mit Fettsäuren, insbesondere geradkettigen gesättigten Fettalkoholen mit 6 bis 30 Kohlenstoffatomen, vorzugsweise mit 8 bis 22 Kohlenstoffatomen, bevorzugt Laurylalkohol, Cetylalkohol, Stearylalkohol, Lignocerylalkohol oder Myristylalkohol;
• (iii) Fettsäuren oder deren Estern mit Fettalkoholen, vorzugsweise geradkettigen gesättigten Fettsäuren mit 8 bis 30 Kohlenstoffatomen, bevorzugt Caprylsäure, Caprinsäure, Undecansäure, Laurinsäure, Palmitinsäure, Stearinsäure oder Arachinsäure;
• (iv) Triterpenen, insbesondere Squalen oder Squalan;
• (v) natürlichen oder synthetischen Wachsen, insbesondere pflanzlichen Wachsen, tierischen Wachsen, mineralischen Wachsen oder petrochemischen Wachsen, vorzugsweise Bienenwachs, Wollwachs, Carnaubawachs, Candelillawachs, Cetylpalmitat, Wachsen auf Basis von Glycerintrifettsäureestern, Paraffinwachsen oder Reiswachs; und
• (vi) deren Mischungen und Kombinationen

ausgewählt ist.With regard to the carrier or matrix material, this is preferably selected from waxes, lipids or polymers. Particularly good results are achieved in the context of the present invention, when the carrier or matrix material from the group of

• (i) glycerides and / or glycerol esters, in particular di- or triglycerides and / or glycerol or glycerol triesters, preferably di- or triglycerides and / or glycerol or glycerol triesters of straight-chain saturated fatty acids having 8 to 30 carbon atoms, preferably di- or triglycerides and / or glycerol or glycerol triesters of caprylic acid, capric acid, undecanoic acid, lauric acid, palmitic acid, stearic acid and / or arachic acid;
• (Ii) fatty alcohols or their esters with fatty acids, in particular straight-chain saturated fatty alcohols having 6 to 30 carbon atoms, preferably having 8 to 22 carbon atoms, preferably lauryl alcohol, cetyl alcohol, stearyl alcohol, lignoceryl alcohol or myristyl alcohol;
• (iii) fatty acids or their esters with fatty alcohols, preferably straight-chain saturated fatty acids having 8 to 30 carbon atoms, preferably caprylic, capric, undecanoic, lauric, palmitic, stearic or arachidic acid;
• (iv) triterpenes, especially squalene or squalane;
• (v) natural or synthetic waxes, in particular vegetable waxes, animal waxes, mineral waxes or petrochemical waxes, preferably beeswax, wool wax, carnauba wax, candelilla wax, cetyl palmitate, waxes based on glycerol trifatty acid esters, paraffin waxes or rice wax; and
• (vi) their mixtures and combinations

is selected.

The amount of carrier or matrix material used can vary within wide ranges. According to the invention it can be provided that the nanoparticles, the carrier or matrix material in an amount ranging from 5 to 99 wt .-%, in particular in the range of 10 to 95 wt .-%, preferably in the range of 15 to 90 wt. -%, preferably in the range of 20 to 85 wt .-%, particularly preferably in the range of 25 to 80 wt .-%, based on the nanoparticles included.

With regard to the mechanical stability of the nanoparticles according to the invention and the controlled release of the incorporated or incorporated active substances from the nanoparticles and the formation of the membrane system, it has proved to be advantageous if the nanoparticles comprise the at least one carrier or matrix material and the at least one dispersant in a defined weight ratio relative to each other. Particularly good results are achieved within the scope of the present invention if the nanoparticles contain the at least one carrier and / or matrix material and the at least one dispersant in a weight-related quantitative ratio of carrier and / or matrix material to dispersant (carrier and / or matrix material: dispersant ) in the range from 1: 100 to 100: 1, in particular in the range from 1:20 to 20: 1, preferably in the range from 1:10 to 10: 1, preferably in the range from 1: 5 to 5: 1.

In addition, it is achieved by the aforementioned defined proportions of the ingredients used that larger amounts of the first active ingredient and optionally other active ingredients in the carrier or matrix material can be incorporated or incorporated without destabilizing the nanoparticles as such by too large amounts of active ingredient.

• (i) pflanzlichen Ölen, insbesondere ätherischen Ölen;
• (ii) antibakteriellen und/oder antimikrobiellen Wirkstoffen; und
• (iii) deren Mischungen und Kombinationen

ausgewählt.The selection of active ingredients which can be incorporated or incorporated into the nanoparticles is extremely diverse. In particular, in the context of the present invention, active substances which can be used in the field of oral hygiene or for the treatment of colds or hoarseness are incorporated into the nanoparticles or incorporated. Preferably, in this context, the first active ingredient from the group of

• (i) vegetable oils, especially essential oils;
• (ii) antibacterial and / or antimicrobial agents; and
• (iii) their mixtures and combinations

selected.

According to the invention, the vegetable oils, in particular the essential oils, are from the group of mint oil, in particular peppermint oil, eucalyptus oil, thyme oil, clove oil, citronella oil, chamomile oil, orange oil, rosemary oil, lemon oil, sage oil, wintergreen oil and mixtures thereof or combinations, preferably peppermint oil and wintergreen oil. selected. On the one hand, essential oils provide a sense of freshness in the mouth, but on the other hand, they also have numerous medically relevant effects, such as, for example, anti-inflammatory, antibacterial or expectoration-promoting effects.

As far as the antibacterial or antimicrobial agents are concerned, they are preferably selected from the group of pharmaceutically usable antiseptics, in particular triclosan, cetylpyridinium chloride, chlorhexamed, chlorhexidine, octenidine, cetrimonium bromide (cetyltrimethylammonium bromide) and mixtures or combinations thereof. Antimicrobial or antibacterial agents are usually used both for the treatment of colds and in the context of dental prophylaxis for the prevention of plaque and caries.

The amount of the at least one first active substance in the nanoparticles according to the invention can vary within wide ranges. In the context of the present invention, it is preferred if the nanoparticles contain the first active ingredient in an amount in the range from 0.1 to 80% by weight, in particular in the range from 0.5 to 75% by weight, preferably in the range from 1 to 70 wt .-%, preferably in the range of 5 to 65 wt .-%, based on the nanoparticles included.

In the context of the present invention, it has surprisingly been found that, owing to the combination of the carrier or matrix materials and dispersants used according to the invention, on the one hand with the use of at least one preferably acidic glycosaminoglycan, it is possible to introduce particularly large amounts of active ingredient or active ingredients into the nanoparticles according to the invention , wherein the nanoparticles still remain stable and no unwanted premature leakage of active ingredients occurs.

As regards the envisaged preferably acidic glycosaminoglycan in particular, it has proved to be advantageous if it is hyaluronic acid or its physiologically tolerated derivatives or salts, in particular the sodium salt of hyaluronic acid.

Chemically, hyaluronic acid is a macromolecular chain of disaccharides based on D-glucuronic acid and N-acetyl-D-glucosamine linked by a beta-1,3-glucosidic linkage. In turn, the disaccharides are linked together via a beta-1,4-glucosidic bond to a polymeric chain. In general, a hyaluronic acid polymer consists of 250 to 50,000 disaccharide units.

In the context of the present invention, it has been found that the ability of hyaluronic acid to be able to bind large amounts of water improves the film formation of the nanoparticles according to the invention on the mucous membrane in the mouth or in the oral cavity and thus to an increased uptake of the active ingredients at the sites of action As hyaluronic acid lowers the viscosity of the mucous membrane in the oral cavity and thus the mobility of the lipids in the mucosal cells. In addition, the hyaluronic acid causes a strong wetting of the mucous membrane, which allows effective relief of the symptom of dry mouth.

Moreover, it has completely surprisingly been found in the context of the present invention that the formation of the membrane structure is further improved by the use of hyaluronic acid. In the context of the present invention, it is assumed - without wishing to be limited to this theory - that the hyaluronic acid leads to a stabilization of the interfaces between dispersant on the one hand and carrier or matrix material on the other hand. Due to the stabilized interfaces, an even finer membrane structure is formed, which on the one hand increases the maximum absorbable amount of active ingredient and on the other hand further improves the mechanical stability of the nanoparticles while simultaneously optimizing the release behavior.

In connection with the at least one preferably acidic glycosaminoglycan or hyaluronic acid, it has also proved to be advantageous if the at least one preferably acidic glycosaminoglycan or its physiologically tolerated derivatives or salts, in particular hyaluronic acid or its physiologically tolerated derivatives or salts Molecular weight, in particular a number-average molecular weight, in the range from 10,000 to 3,000,000 Da, in particular in the range from 15,000 to 2,500,000 Da, preferably in the range from 20,000 to 2,000,000 Da, preferably in the range from 50,000 to 1,500,000 Da, having.

Surprisingly, the aforementioned effects can be achieved even with relatively small amounts of glycosaminoglycan or hyaluronic acid. Thus, it has surprisingly been found in the context of the present invention that it is sufficient if the nanoparticles contain the at least one preferably acidic glycosaminoglycan or its physiologically tolerated derivatives or salts, in particular hyaluronic acid or its physiologically tolerable salts, in an amount in the range of 0, 01 to 10 wt .-%, in particular in the range of 0.1 to 8 wt .-%, preferably in the range of 0.5 to 5 wt .-%, preferably in the range of 1 to 4 wt .-%, based on the nanoparticles, included.

The preferably acid glycosaminoglycan can be incorporated into the nanoparticles as well as outside or at the surface of the nanoparticles. In particular, in the context of the present invention, the second active ingredient in the form of the at least one preferably acidic glycosaminoglycan or its physiologically compatible derivatives or salts, in particular hyaluronic acid or its physiologically acceptable salts, can be incorporated into the nanoparticles and / or deposited and / or deposited on the nanoparticles be. Similarly, it can be provided that the second active ingredient in the form of at least one preferably acidic glycosaminoglycan or its physiologically acceptable derivatives or salts, in particular hyaluronic acid or its physiologically acceptable salts, on the upper and / or boundary surface of the nanoparticles on and / or superimposed is.

• (i) Aromen und/oder Geschmacksbildnern, insbesondere natürlichen oder naturidentischen Aromen oder Geschmacksbildnern;
• (ii) Vitaminen und/oder deren Vorstufen und/oder Präkursoren; und
• (iii) deren Mischungen und Kombinationen

ausgewählt sein.Moreover, it is preferred in the context of the present invention if the nanoparticles have at least one further auxiliary or ingredient. Such an auxiliary or ingredient may in particular from the group of

• (i) flavorings and / or flavoring agents, in particular natural or nature-identical flavorings or flavoring agents;
• (ii) vitamins and / or their precursors and / or precursors; and
• (iii) their mixtures and combinations

be selected.

The flavors or flavoring agents used may in particular be those substances which lead to a sense of freshness in the mouth or fresh breath, as is customarily desired in the context of oral hygiene or oral hygiene. Preferably, the flavors or flavors are from the group of phytochemicals, in particular from the group of phenolic compounds, in particular simple phenols, polyphenols, xanthones, phenylpropanoids, stilbenes and their glycosides; isoprenoid compounds, in particular terpenes, preferably menthol, cineol or menthone; alkaloids; and their mixtures or combinations; selected. In the context of the present invention, particular preference is given to selecting secondary plant substances which can be isolated from mint or peppermint, for example menthol, menthone of cineol. The aforementioned substances have antimicrobial and expektorationsfördernd, moreover, they produce a pleasant sensation of freshness in the mouth.

As regards the vitamins or their precursors or precursors, they are preferably selected from the group of fat-soluble vitamins or their precursors or precursors, in particular vitamin A, preferably in the form of retinol; Vitamin D; Vitamin E, preferably in the form of alpha tocopherol; Vitamin K; and mixtures or combinations thereof.

The amount of auxiliaries or ingredients used is equally variable. Auxiliaries or ingredients can also be introduced in large quantities into the nanoparticles on account of the inventive combination of the carrier or matrix material with the dispersant and the at least one preferably acidic glycosaminoglycan. According to the invention, it is preferred if the nanoparticles contain the auxiliary or ingredient in an amount in the range from 0.01 to 60% by weight, in particular in the range from 0.1 to 50% by weight, preferably in the range from 0, 5 to 40 wt .-%, preferably in the range of 1 to 30 wt .-%, based on the nanoparticles containing.

In connection with the above-described "plaster effect" or the area-wide formation of a film on the mucous membrane of the oral cavity, moreover, the average particle diameter of the nanoparticles has proven to be particularly relevant. An optimal surface coverage or film formation is achieved in the context of the present invention, when the nanoparticles under storage and / or use conditions an average particle diameter, in particular an average particle diameter D50, in the range of 8 to 12,000 nm, in particular in the range of 20 to 10,000 nm , preferably in the range from 50 to 8,000 nm, preferably in the range from 75 to 5,000 nm, particularly preferably in the range from 150 to 2,500 nm.

In the context of the present invention, storage or application conditions are understood in particular to mean a temperature of 25 ° C. and atmospheric pressure (101.325 kPa).

The methods for determining the particle size of the nanoparticles according to the invention are well known to those skilled in the art as such. In particular, the particle sizes can be determined by light microscopy, electron microscopy and comparable methods. For further information with regard to the particle size, reference is made in particular to the above statements in accordance with the text section on the term "nanoparticles" in order to avoid unnecessary repetitions.

As regards the geometric shape of the nanoparticles under storage or application conditions in particular, it is preferably at least substantially spherical or stretched or drop-shaped, in particular at least substantially spherical, or drop-shaped, preferably at least substantially spherical.

In addition, it may be advantageous with respect to the nanoparticles according to the invention, if these at least one additive, in particular selected from the group of processing aids, colorants, buffers, fragrances, fragrances, extenders, binders, wetting agents and / or preservatives , pH adjusters, pH buffering agents, thickening agents, flavorings, flavorings, sweeteners and sweeteners, acidulants, stabilizers and / or antiseptics and mixtures thereof.

The nanoparticles according to the invention may be present for administration or administration in various administration or application forms:
According to a first embodiment of the invention, provision may be made for the nanoparticles to be present in a solid and / or at least substantially liquid-free application and / or dosage form.

In this context, it is particularly preferred if the nanoparticles are incorporated in dragees, tablets, compactates or the like, or present as dragees, tablets, compactates or the like. In the context of the present invention, such dragees, tablets, compactates or the like can be obtained by pressing a multiplicity of nanoparticles.

In particular, it can also be provided according to the invention that the nanoparticles are present or incorporated in a carrier substance, preferably based on sugars, sugar substitutes or sweeteners. In particular, the embodiment of the application or dosage form in the sense of a lozenge is to be understood as being introduced into a carrier substance, the carrier substance being dissolved when it is sucked in the mouth by contact with saliva and the nanocapsules being released in this manner.

According to a further preferred embodiment of the present invention, it may be provided that the nanoparticles are introduced into a pharmaceutically usable capsule material, in particular a capsule shell, preferably based on gelatin. However, all other capsule materials which can be used in the field of medical encapsulation of active ingredients are also used. Their selection belongs to the usual actions of the expert and requires no further explanation at this point.

The above-listed application or administration forms are in no way to be understood as exhaustive or restrictive. The provision of application or dosage forms which contain the nanoparticles according to the invention is within the ordinary skill of the art and requires no further explanation.

Furthermore, according to a further embodiment of the present invention, provision may be made for the nanoparticles to be present in liquid administration or administration form, in particular for application or administration to the human or animal body.

In this context, it is particularly preferred according to the invention if the nanoparticles are present as a dispersion. Such a dispersion is preferably obtained by introducing the nanoparticles into at least one solvent and / or dispersion medium, in particular wherein the dispersion is aqueous, organic or aqueous-organic.

• (a) Bereitstellen einer ersten, insbesondere organischen Phase, wobei die erste Phase mindestens ein Träger- und/oder Matrixmaterial; mindestens ein Dispergiermittel; und (a) mindestens einen topisch applizierbaren ersten Wirkstoff aufweist;
• (b) Bereitstellen einer zweiten, insbesondere wässrigen Phase, wobei die zweite Phase mindestens ein Dispersionsmittel, insbesondere Wasser; (b) mindestens einen zweiten Wirkstoff in Form eines vorzugsweise sauren Glykosaminoglykans oder dessen physiologisch verträglichen Derivaten oder Salzen; gegebenenfalls eine mit dem Dispersionsmittel, insbesondere Wasser, mischbare Flüssigkeit, insbesondere mindestens ein Polyalkylenglykol, vorzugsweise Polyethylenglykol, und/oder mindestens einen mehrwertigen Alkohole, vorzugsweise Glycerin, aufweist;
• (c) Vermengen und/oder Vermischen, insbesondere mittels Rühren, der ersten, insbesondere organischen Phase mit der zweiten, insbesondere wässrigen Phase, unter Erwärmung auf eine Temperatur oberhalb des Schmelz- und/oder Erweichungspunktes des Träger- und/oder Matrixmaterials, insbesondere unter Ausbildung einer flüssig-kristallinen Phase insbesondere des Träger- und/oder Matrixmaterials;
• (d) Abkühlen der in Schritt (c) erhaltenen Mischung, insbesondere unter Rühren, unterhalb des Schmelz- und/oder Erweichungspunktes des Träger- und/oder Matrixmaterials zum Erhalt der in einer Dispersion befindlichen wirkstoffhaltigen Nanopartikel; und
• (e) gegebenenfalls Entfernen der flüssigen Komponenten und/oder Bestandteile, insbesondere Wasser, vorzugsweise mittels Trocknung, bevorzugt mittels Gefriertrocknung, zum Erhalt der getrockneten und/oder isolierten wirkstoffhaltigen Nanopartikel.

The active substance-containing nanoparticles, as described above, are obtainable in particular by a process comprising the following steps:

• (A) providing a first, in particular organic phase, wherein the first phase at least one carrier and / or matrix material; at least one dispersant; and (a) at least one topically applied first active ingredient;
• (b) providing a second, in particular aqueous phase, wherein the second phase comprises at least one dispersant, in particular water; (B) at least one second active ingredient in the form of a preferably acid glycosaminoglycan or its physiologically acceptable derivatives or salts; optionally a liquid which is miscible with the dispersing agent, in particular water, in particular at least one polyalkylene glycol, preferably polyethylene glycol, and / or at least one polyhydric alcohol, preferably glycerol;
• (C) mixing and / or mixing, in particular by means of stirring, the first, in particular organic phase with the second, especially aqueous phase, with heating to a temperature above the melting and / or softening point of the carrier and / or matrix material, in particular Forming a liquid-crystalline phase in particular of the carrier and / or matrix material;
• (d) cooling the mixture obtained in step (c), in particular with stirring, below the melting and / or softening point of the carrier and / or matrix material to obtain the active ingredient-containing nanoparticles present in a dispersion; and
• (E) optionally removing the liquid components and / or constituents, in particular water, preferably by means of drying, preferably by freeze-drying, to obtain the dried and / or isolated active ingredient-containing nanoparticles.

Moreover, it can be provided according to the invention that, in particular in step (d), the concentration of the nanoparticles in the dispersion is deliberately adjusted. This can be done according to the invention by adding additional solvents, preferably aqueous solvents, to the dispersion, in particular in step (d). According to a particularly preferred embodiment, water or water-miscible liquids, preferably polyalkylene glycols, preferably polyethylene glycol or polyhydric alcohols, in particular glycerol, are used as aqueous solvents.

The uses of the nanoparticles according to the invention are extremely varied, as stated below:
According to a second aspect of the invention, the nanoparticles described above can be used in particular for use in prophylactic or curative treatment, in particular topical treatment, of the oral or pharyngeal mucosa or the oral cavity.

In particular, the nanoparticles according to the invention for use in the prophylactic and / or curative treatment, in particular topical treatment of dry mouth, preferably in smokers, and / or hoarseness and / or inflammatory diseases of the mouth and throat, especially colds and / or influenza infections , and / or for use in general oral and / or dental care and / or general oral and / or dental hygiene.

Another object of the present invention is the use of nanoparticles, as described above, for prophylactic and / or curative treatment, in particular topical treatment, the oral and / or pharyngeal mucosa and / or in the oral cavity.

In addition, the nanoparticles according to the invention are for use in the prophylactic and / or curative treatment, in particular topical treatment, of dry mouth, preferably in smokers, and / or hoarseness and / or inflammatory diseases of the oropharynx, especially colds and / or influenza Infections, and / or in general oral and / or dental care and / or in general oral and / or dental hygiene suitable.

Likewise, the nanoparticles of the invention as described above are suitable for the manufacture of a medicament or therapeutic for prophylactic and / or curative treatment, in particular topical treatment, of the oral and / or pharyngeal mucosa and / or in the oral cavity.

Finally, the nanoparticles according to the present invention may also be used for the manufacture of a medicament or therapeutic for prophylactic and / or curative treatment, in particular topical treatment, of dry mouth, preferably in smokers, and / or hoarseness and / or inflammatory diseases of the oropharynx, in particular Colds and / or flu infections, and / or for the manufacture of a medicament or therapeutic agent for use in general oral and / or dental care and / or in general oral and / or dental hygiene.

• (a) Bereitstellen einer ersten, insbesondere organischen Phase, wobei die erste Phase mindestens ein Träger- und/oder Matrixmaterial; mindestens ein Dispergiermittel; und (a) mindestens einen topisch applizierbaren ersten Wirkstoff aufweist;
• (b) Bereitstellen einer zweiten, insbesondere wässrigen Phase, wobei die zweite Phase mindestens ein Dispersionsmittel, insbesondere Wasser; (b) mindestens einen zweiten Wirkstoff in Form eines vorzugsweise sauren Glykosaminoglykans oder dessen physiologisch verträglichen Derivaten oder Salzen; gegebenenfalls eine mit dem Dispersionsmittel, insbesondere Wasser, mischbare Flüssigkeit, insbesondere mindestens ein Polyalkylenglykol, vorzugsweise Polyethylenglykol, und/oder mindestens einen mehrwertigen Alkohole, vorzugsweise Glycerin, aufweist;
• (c) Vermengen und/oder Vermischen, insbesondere mittels Rühren, der ersten, insbesondere organischen Phase mit der zweiten, insbesondere wässrigen Phase, unter Erwärmung auf eine Temperatur oberhalb des Schmelz- und/oder Erweichungspunktes des Träger- und/oder Matrixmaterials, insbesondere unter Ausbildung einer flüssig-kristallinen Phase insbesondere des Träger- und/oder Matrixmaterials;
• (d) Abkühlen der in Schritt (c) erhaltenen Mischung, insbesondere unter Rühren, unterhalb des Schmelz- und/oder Erweichungspunktes des Träger- und/oder Matrixmaterials zum Erhalt der in einer Dispersion befindlichen wirkstoffhaltigen Nanopartikel.

Another object of the present invention is - according to a third aspect of the invention - a method for the preparation of active ingredient-containing nanoparticles, which are suitable for topical application to the oral mucosa or in the oral cavity, preferably as described above, wherein the method following steps include:

• (A) providing a first, in particular organic phase, wherein the first phase at least one carrier and / or matrix material; at least one dispersant; and (a) at least one topically applied first active ingredient;
• (b) providing a second, in particular aqueous phase, wherein the second phase comprises at least one dispersant, in particular water; (B) at least one second active ingredient in the form of a preferably acid glycosaminoglycan or its physiologically acceptable derivatives or salts; optionally a liquid which is miscible with the dispersing agent, in particular water, in particular at least one polyalkylene glycol, preferably polyethylene glycol, and / or at least one polyhydric alcohol, preferably glycerol;
• (C) mixing and / or mixing, in particular by means of stirring, the first, in particular organic phase with the second, especially aqueous phase, with heating to a temperature above the melting and / or softening point of the carrier and / or matrix material, in particular Forming a liquid-crystalline phase in particular of the carrier and / or matrix material;
• (d) cooling the mixture obtained in step (c), in particular with stirring, below the melting and / or softening point of the carrier and / or matrix material to obtain the active ingredient-containing nanoparticles present in a dispersion.

According to a particular embodiment of the process according to the invention, it may be provided that in step (d) optionally further dispersing agent, in particular water, and / or at least one water-miscible liquid, preferably at least one polyalkylene glycol, preferably polyethylene glycol, and / or at least one polyhydric alcohol , preferably glycerol, is used. In this way, the concentration of the nanoparticles in the dispersion can be controlled in a targeted manner.

Finally, it may also be provided that, in a further step (e), liquid components and / or constituents, in particular water, are preferably removed by drying, preferably by freeze drying, to obtain dried and / or isolated active ingredient-containing nanoparticles.

The implementation of the method according to the invention as such is in the usual practice of the skilled person and requires no further implementation at this point.

Another object of the present invention - according to a fourth aspect of the invention - is also a dispersion containing active ingredient-containing nanoparticles, in particular nanoparticles as described above, and which is suitable for topical application to the oral mucosa or in the oral level ; and wherein the nanoparticles comprise at least one carrier and / or matrix material on the one hand and at least one dispersant on the other hand and wherein the nanoparticles (a) contain at least one first active substance preferably incorporated and / or incorporated into the carrier and / or matrix material, in particular topically administrable; and wherein the dispersion and / or the Nanoparticles (b) contains or contain at least one second active ingredient in the form of a preferably acidic glycosaminoglycan or its physiologically acceptable derivatives or salts.

In the context of the present invention, the dispersion may be aqueous, organic or aqueous-organic. Preferably, the dispersion of the invention is formed aqueous-organic. Likewise, the dispersion can be formed as an emulsion or suspension, in particular as an emulsion, preferably as an oil-in-water emulsion.

The dispersion according to the invention usually contains at least one dispersant, preferably water. The amount of dispersant used can vary widely. Preferably, the dispersion has the at least one dispersant in an amount in the range of 10 to 90 wt .-%, in particular in the range of 15 to 85 wt .-%, preferably in the range of 20 to 80 wt .-%, preferably in the range of 25 to 75 wt .-%, based on the dispersion, on.

In addition, the dispersion of the invention may contain at least one further, preferably water-miscible liquid. According to the invention, the dispersion preferably contains such a liquid in an amount in the range from 1 to 80% by weight, in particular in the range from 5 to 75% by weight, preferably in the range from 10 to 70% by weight, preferably in the range from 15 to 65 wt .-%, based on the dispersion.

In this context, the further, preferably water-miscible, liquid may be selected from water-soluble or water-dispersible polyalkylene glycols, in particular polyethylene glycol, and / or polyhydric alcohols, in particular glycerol.

The amount of nanoparticles used in the dispersion can vary within wide limits and depends in particular on the particular field of application of the dispersion. The dispersion usually contains the nanoparticles in a volume-related amount in the range of 1 to 90% by volume, in particular in the range of 5 to 85% by volume, preferably 10 to 80% by volume, particularly preferably 15 to 75% by volume. %, based on the dispersion.

Similarly, it may be provided that the dispersion contains the nanoparticles in a mass-based amount in the range from 5 to 80% by weight, in particular in the range from 10 to 75% by weight, preferably in the range from 15 to 70% by weight, based on the dispersion contains.

As far as the amount of glycosaminoglycan contained in the dispersion is concerned, it is variable. According to a preferred embodiment, the dispersion (b) the second active ingredient in the form of at least one preferably acid glycosaminoglycan or its physiologically acceptable salts in an amount in the range of 0.01 to 5 wt .-%, in particular in the range of 0.05 to 4 wt .-%, preferably in the range of 0.1 to 3 wt .-%, based on the dispersion.

According to the invention, with regard to the dispersion according to the invention, the glycosaminoglycan, independently of one another, can be present both inside the nanoparticles as such and outside the nanoparticles, in particular externally attached to the nanoparticles. According to a first embodiment of the present invention, (b) the second active ingredient may be in the form of the at least one preferably acidic glycosaminoglycan or its physiologically acceptable derivatives or salts in the dispersion, in particular the dispersing agent, dispersed and / or dissolved. Equally, it may be provided that (b) the second active substance is incorporated in the nanoparticles in the form of the at least one preferably acidic glycosaminoglycan or its physiologically compatible derivatives or salts and / or is attached to and / or deposited on the nanoparticles. In addition, it can be provided according to the invention that (b) the second active ingredient in the form of the at least one preferably acidic glycosaminoglycan or its physiologically compatible derivatives or salts is attached to and / or deposited on the upper and / or boundary surface of the nanoparticles, as before cited.

In particular, in order to tailor the dispersion according to the invention with regard to its intended use, it may also be provided that the dispersion according to the invention contains at least one viscosity-increasing agent and / or one thickener. In particular, such a viscosity-increasing agent or thickening agent can be selected from the group of polysaccharides, in particular cellulose, cellulose derivatives or xanthans, polyalkyl acrylates, polyvinylpyrrolidones, polyalkylcyanoacrylates, acrylic polymers, polylactates, polylactides, bentonites, silicic acids, carbomers and mixtures thereof.

The amount of viscosity-increasing agent or thickening agent used is variable and depends on the desired viscosity. According to the invention, the dispersion contains the viscosity-increasing agent or the thickening agent preferably in an amount in the range of 0.01 to 20 wt .-%, in particular in the range 0.1 to 10 wt .-%, preferably in the range 0.5 to 5 wt .-%, preferably in the range of 1 to 3 wt .-%, based on the dispersion.

The dispersion of the invention may have different viscosities, in particular Brookfield viscosities. According to the invention, it is preferred if the dispersion under storage and / or use conditions, in particular at 25 ° C., has a Brookfield viscosity in the range from 500 to 100,000 mPas, in particular in the range from 1,000 to 90,000 mPas, preferably in the range from 2,000 to 80,000 mPas, preferably in the range of 2,500 to 70,000 mPas.

In addition, it has proven to be expedient to adjust the dispersion according to the invention to defined pH values. This should be done according to the invention, in particular in adaptation to the particular application. Thus, dispersions which are used for daily use as part of the basic prophylaxis of plaque or tooth decay, with regard to the pH of significantly only for the short-term and medically indicated or therapeutic use, for example, for the treatment of colds, a distinguish such dispersion. The setting of a suitable pH is within the ordinary skill of the art, so there is no need for further discussion in this regard.

In this context, it is preferred according to the invention if the dispersion contains at least one acid and / or base, in particular for forming a buffer system.

Similarly, it may be provided that the dispersion contains at least one buffer system. Such a buffer system may in particular be selected from the group of carbonate buffers, citrate buffers or phosphate buffers, in particular phosphate buffers. Basically, the use of all known pharmaceutically usable buffer systems is conceivable.

Furthermore, it can be provided in the context of the present invention that the dispersion comprises at least one additive, in particular selected from the group of processing aids, colorants, buffers, fragrances, fragrances, extenders, binders, wetting agents and / or preservatives , pH adjusters, pH buffering agents, thickening agents, flavorings, flavorings, sweeteners and sweeteners, acidulants, stabilizers and / or antiseptics and mixtures thereof.

The dispersion according to the invention can be present in various application or administration forms. The following options are preferred embodiments, but should not be considered in any way as exhaustive.

According to a first preferred embodiment of the invention, it may be provided that the dispersion is present as a liquid administration or administration form. In particular, the dispersion according to the invention in this context may be present as fluid, mouthwash, mouthwash, juice, gargle solution or the like.

According to another preferred embodiment of the invention, it may be provided that the dispersion is in the form of a pasty or semi-solid application or dosage form. In particular, the dispersion of the invention in this context may be formed as a cream, ointment, lotion or the like.

Finally, it can also be provided that the dispersion according to the invention is present as an aerosol-like application or dosage form. In this connection, it is particularly preferred if the dispersion is formed as a spray, spray composition or the like.

The dispersion according to the invention is particularly suitable for use in prophylactic and / or curative treatment, in particular topical treatment, the oral and / or pharyngeal mucosa and / or the oral cavity.

In particular, the dispersion of the present invention is for use in prophylactic and / or curative treatment, especially topical treatment, of dry mouth, preferably in smokers, and / or hoarseness and / or inflammatory diseases of the mouth and mouth Throat area, especially colds and / or flu infections, and / or for use in general oral and / or dental care and / or in general oral and / or dental hygiene suitable.

Finally, the present invention - according to a fifth aspect of the invention - the use of a dispersion, as described above, for prophylactic and / or curative treatment, in particular topical treatment, the oral and / or pharyngeal mucosa and / or in the oral cavity.

In particular, the present invention relates to the use of a dispersion according to the present invention for prophylactic and / or curative treatment, in particular topical treatment, of dry mouth, preferably in smokers, and / or hoarseness and / or inflammatory diseases of the oropharynx, especially colds and / or flu infections, and / or use in general oral and / or dental care and / or general oral and / or dental hygiene.

Another use of the dispersion as described above is in the preparation of a medicament or therapeutic for prophylactic and / or curative treatment, in particular topical treatment, the oral and / or pharyngeal mucosa and / or in the oral cavity.

Also, the dispersion of the invention for the manufacture of a medicament or therapeutic for prophylactic and / or curative treatment, especially topical treatment of dry mouth, preferably in smokers, and / or hoarseness and / or inflammatory diseases of the mouth and throat, especially colds and / or influenza infections, and / or for the manufacture of a medicament or therapeutic agent for use in general oral and / or dental care and / or in general oral and / or dental hygiene.

Finally, it is object of the present invention - in accordance with a sixth aspect of the invention n - a Pharmaceutical or application form, especially in solid, liquid, paste or aerosol-like form which contains the active substance-containing nanoparticle described above.

Likewise, the subject of the present invention is a dosage form, in particular in liquid, pasty or aerosol-like form, which contains the dispersion of the present invention described above.

It goes without saying that embodiments, embodiments, advantages and the like, which have been carried out for the purpose of avoiding unnecessary repetition only to an aspect of the invention, of course, also apply accordingly with respect to the other aspects of the invention.

Further embodiments, modifications and variations as well as advantages of the present invention will be readily apparent to and realizable by those skilled in the art upon reading the description without departing from the scope of the present invention.

The present invention will be further illustrated by the following embodiments, which by no means limit the present invention.

WORKING EXAMPLES

First of all, the nanoparticles according to the invention as such as well as dispersions or administration and administration forms which contain the nanoparticles according to the invention were prepared and characterized in terms of their properties and activity and compared with non-inventive administration and administration forms. In addition, non-inventive dispersions of active ingredient-containing liposomes were provided for comparison purposes. The embodiments according to the invention and the comparison nanoparticles and liposomes were introduced into mouthwash solutions in order to investigate the effect on the user or patient.

1. Preparation of inventive dispersions of nanoparticles

Dispersions of active ingredient-containing nanoparticles according to the invention were provided by means of the method according to the invention:
First, a first organic phase, which in addition to the at least one carrier or matrix material at least one dispersant and at least one in particular partially fat-soluble or amphiphilic Contained active ingredient provided. Further, a second aqueous phase containing water as a dispersant was provided. In addition, the second aqueous phase contained as acid glycosaminoglycan the sodium salt of hyaluronic acid and glycerin as another dispersant.

Subsequently, the first organic and the second aqueous phase were mixed together or mixed with stirring and simultaneous heating to a temperature above the melting or softening point of the carrier or matrix material. Thereafter, the mixture obtained was cooled with stirring to temperatures below the melting or softening point of the carrier or matrix material, so that the nanoparticles according to the invention could be formed in the dispersion to obtain a membrane structure.

The following Table 1 shows the formulations of the dispersions of nanoparticles A to C according to the invention. The stated weight-based quantities are based on the dispersion. Table 1: Formulations for dispersions of nanoparticles according to the invention Nanoparticles A Nanoparticles B Nanoparticles C ingredient Amount [wt%] Amount [wt%] Amount [wt%] squalane 25-50 25-50 25-50 water 10-25 10-25 10-25 Carrier / matrix material I 10-25 10-25 10-25 Carrier / matrix material II 5-10 5-10 5-10 dispersants 5-10 5-10 5-10 flavoring 1-5 1-5 1-5 PEG-100 stearate 1-5 1-5 1-5 glyceryl 1-5 1-5 1-5 CTAB 1-5 1-5 1-5 sodium hyaluronate 2-8 2-8 2-8 Sweeteners I 0.1-1 0.1-1 0.1-1 menthol 0.1-1 0.1-1 0.1-1 acidity regulator <0.1 <0.1 <0.1 Sweeteners II <0.1 <0.1 <0.1 Wintergreen oil 3.6 - 3.6 peppermint oil 1.8 - 1.8 chlorhexidine - 2.2 - retinol - - 2.0 tocopherol - - 2.0

As can be seen from Table 1 above, the dispersions A to C of the nanoparticles according to the invention differed with respect to the active ingredients contained. The nanoparticles of dispersion A contained a combination of wintergreen oil and peppermint oil and are preferably used in mouthwashes for dental prophylaxis as so-called mouthwash. The nanoparticles of dispersion B according to the invention contained, in addition to the flavor menthol as antimicrobial agent chlorhexidine and are used in particular in mouthwashes used for the treatment of inflammatory diseases in the mouth and / or throat. In addition to wintergreen and peppermint oils, the nanoparticles of dispersion C according to the invention additionally contained the vitamins retinol (vitamin A1) and tocopherol (vitamin E). Such nanoparticles are preferably used in special mouthwashes for the relief of dry mouth and hoarseness, as occurs in particular in smokers.

After preparation of the dispersions according to the invention in which the nanoparticles were present, these were characterized in terms of their properties. The relevant results are shown in Table 2 below: TABLE 2 Properties of the dispersions of nanoparticles according to the invention property Nanoparticles A Nanoparticles B Nanoparticles C Appearance [at 25 ° C] viscous dispersion viscous dispersion viscous dispersion odor characteristic characteristic characteristic colour White White White Viscosity at 25 ° C [mPas] <50,000 <20,000 <80,000 active substance Peppermint oil, wintergreen oil chlorhexidine Peppermint oil, wintergreen oil, retinol, tocopherol function Aroma (fresh breath) antiseptic Special application for smokers against dry oral mucosa Active substance content 5.0 ± 0.5 2.2 ± 0.1 9.4 ± 0.5 base wax Beeswax / cetyl palmitate Beeswax / cetyl palmitate Based wax / cetyl palmitate

2. Provision of comparative dispersions

In order to be able to compare the dispersions A to C according to the invention with respect to their properties with noninventive dispersions, the comparative dispersions A 'to C' which contained nano-particles not according to the invention were provided. The nanoparticles contained in the dispersions A 'to C' also contained in the case of A 'wintergreen oil and peppermint oil as active ingredients, in the case of B' chlorhexidine as the active ingredient and in the case of C 'wintergreen and peppermint oil and retinol and tocopherol as active ingredients. In contrast to the dispersions according to the invention, however, the comparative dispersions A 'to C' or comparative nanoparticles did not contain any hyaluronic acid. The relative to the inventive dispersions A to C missing weight-based fraction of hyaluronic acid was, based on the dispersion, each half replaced by water and half by squalane.

In addition, the comparative dispersions A "to C" were provided, which contained drug-containing liposomes for drug release, the liposomes also in the case of A '' wintergreen oil and peppermint oil as active ingredients, in the case of B '' chlorhexidine as active ingredient and in the case of C '' wintergreen and peppermint oil and retinol and tocopherol as active ingredients contained. Liposomes differ with regard to their internal structure from the nanoparticles according to the invention, since they have no membrane structure based on carrier or matrix material and dispersant in the sense of the present invention. They are significantly more unstable when taking up the same amounts of active substance than the nanoparticles according to the invention, which are at least substantially completely penetrated or interspersed by a membrane system. The comparative dispersions A "to C" also contained no hyaluronic acid.

3. Application and efficacy studies

In order to compare dispersions A to C according to the invention with comparative dispersions A 'to C' and A "to C", mouthwash solutions were used which each contained one of the dispersions. Mouthwashes based on the dispersions A, A 'and A "were used as mouthwashes in dental prophylaxis. Mouthwashes based on the dispersions B, B 'and B' 'were used for the treatment of inflammatory diseases in the mouth and throat. Mouthwashes based on the dispersions C, C 'and C' 'were used for the treatment of hoarseness and dry mouth, especially as it occurs in smokers.

In total, a group of 90 subjects aged 25 to 67, of whom 47 were male and 43 female, were consulted:
As part of dental prophylaxis, 30 healthy volunteers used mouthwashes or mouthwashes based on dispersions A, A 'and A''in the morning and evening in addition to brushing their teeth with a toothbrush. In each case 10 of these subjects received each one of the mouthwashes based on the dispersions A, A 'and A''over a period of 4 days three times a day.

In addition, another 30 of the 90 subjects suffered from inflammatory diseases of the mouth, especially as a result of influenza infections. In each case 10 of these subjects received in each case one of the mouthwashes based on the dispersions B, B 'or B' 'over a period of 4 days three times a day.

30 other subjects who suffered from hoarseness or dry oral mucosa, in particular as a result of smoking, received mouthwash solutions based on the dispersions C, C 'and C' three times a day. In each case 10 of these subjects received in each case one of the mouthwashes based on the dispersions C, C 'or C' 'over a period of 4 days three times a day.

At the end of the treatment period, all subjects were asked to rate the composition being tested for their effects. The results obtained in this regard are explained in detail below.

Dispersions A, A 'and A' '

The assessment of the mouthwashes based on the dispersions A, A 'and A' 'was carried out in particular with regard to the longest possible freshness in the mouth or fresh breath after application of the mouthwash solution. In addition, the subjects assessed the mouthwash solution tested in each case with regard to a pleasant mouthfeel, in particular a wetting of the mucous membranes.

With mouthwashes containing the dispersion A of the invention, an extremely long-lasting sensation of freshness in the mouth could be produced. Due to the controlled and time-delayed release of the active ingredients, the taste of menthol, peppermint oil and wintergreen oil was also well perceived later than 30 minutes after application of the mouthwash solution. In addition, all subjects commented positively on the mouthfeel of the mouthwashes containing the dispersion A of the present invention, since they caused a pleasant wetting of the oral mucosa and prevented it from drying out.

On the other hand, satisfactory results could not be achieved with mouthwashes containing Comparative Dispersions A 'and A' '. In both mouthwash solutions, the freshness effect or peppermint flavor was no longer noticeable after less than 10 minutes. In addition, no long-lasting wetting or moisturizing of the mucous membranes could be achieved with either of the two comparison rinsing solutions. Overall, however, better results were achieved with comparative dispersion A '(active substance-containing nanoparticles without hyaluronic acid) than with comparative dispersion A "(active substance-containing liposomes).

Dispersions B, B 'and B' '

Mouthwashes containing dispersions B, B 'and B "were evaluated by subjects for the alleviation of cold symptoms, particularly oral cavity inflammation. In addition, the subjects assessed the mouthwash solution tested in each case with regard to the mouthfeel, in particular moisturization of the mucous membranes, and the receipt of a fresh breath after application of the mouthwash solution.

Mouthwashes containing the dispersion B according to the invention, lead in all subjects to an extremely rapid decline in inflammatory symptoms. In addition, the inflamed mucous membranes were kept moist, which in addition to the use of an antimicrobial agent for a rapid decline in the inflammatory symptoms or the healing of the inflamed oral mucosa is beneficial. It was also possible with the mouthwash solution containing the dispersion B according to the invention to produce a long-lasting sensation of freshness in the mouth.

By comparison, no satisfactory results could be achieved with the comparative buffing solutions B 'or B ". It took much longer with both comparison rinsing solutions until a symptom subsidence could be observed. Moreover, neither mouthwash solutions based on the comparative dispersion B 'nor the comparative dispersion B''allowed an efficient Wetting of the oral mucosa. Overall, however, better results were achieved with comparative dispersion B '(active substance-containing nanoparticles without hyaluronic acid) than with comparative dispersion B "(active substance-containing liposomes).

Dispersions C, C 'and C' '

The assessment of the mouthwashes containing the dispersions C, C 'and C' ', was carried out in particular with a view to a long-lasting freshness in the mouth after application of the mouthwash and an efficient alleviation of hoarseness and dry mouth by the additional use of tocopherol and retinol ,

With mouthwashes containing the inventive dispersion C, excellent results could be achieved in this regard. As a result of the controlled release of the active ingredients from the nanoparticles over a long period of time, the freshness effect or the peppermint flavor was still pleasant to taste even after more than 30 minutes after application of the mouthwash solution. The additional use of retinol and tocopherol also effectively alleviated the symptoms of dry mouth and hoarseness, especially when compared to mouthwashes containing Dispersions A and B of the invention.

With mouthwashes containing Comparative dispersions C 'and C' ', the freshness effect or peppermint flavor was no longer noticeable after 10 minutes. In addition, the use of retinol and tocopherol without the additional use of hyaluronic acid (comparative dispersion C ') or from liposomes (comparative dispersion C' ') did not satisfactorily alleviate hoarseness or dry mouth. It is therefore to be assumed that the described "patching effect" for wetting the mucous membrane only unfolds its full effect when the nanoparticles according to the invention unfold in combination with acidic glycosaminoglycans. Overall, however, better results were achieved with comparative dispersion C '(active substance-containing nanoparticles without hyaluronic acid) than with comparative dispersion C "(active substance-containing liposomes).

Conclusion

Overall, it can be seen from the results described above that the nanoparticles according to the invention, as a release form of active compounds, ensure a particularly long-lasting effect on account of their special design on the basis of a special membrane structure. In addition, the above-described results show that the effective efficiency of the nanoparticles according to the invention can be enhanced by the additional use of hyaluronic acid. Without wishing to be limited to this theory, the excellent efficiency of action or the controlled release of the active ingredients from the nanoparticles according to the invention can be attributed to the special membrane structure based on the carrier and / or matrix material and the dispersant, which at least substantially completely completes the nanoparticles pervades.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited non-patent literature

• Rawle, A., "Basic Principles of Particle-size Analysis" Surface Coatings International, Part A, Issue 2003/02 [0029]

Claims (21)

Active substance-containing nanoparticles, preferably for topical application on the oral and / or pharyngeal mucosa and / or in the oral cavity, - wherein the nanoparticles have at least one carrier and / or matrix material on the one hand and at least one dispersant on the other hand, and - where the nanoparticles (A) at least one preferably incorporated in the carrier and / or matrix material and / or incorporated, in particular topically applied first active ingredient and (B) at least one second active ingredient in the form of a preferably acidic glycosaminoglycan or its physiologically acceptable derivatives or salts contain. Nanoparticles according to claim 1, wherein the nanoparticles comprise at least one membrane system, in particular wherein the membrane system has at least one membrane and / or membrane structure; in particular wherein the membrane system, in particular the membrane and / or membrane structure, is in contact with the carrier and / or matrix material; and or in particular, wherein the membrane system, in particular the membrane and / or membrane structure, the carrier and / or matrix material in particular at least partially, preferably at least substantially completely surrounds and / or enveloped; and or in particular wherein the membrane system, in particular the membrane and / or membrane structure, the carrier and / or matrix material in particular at least partially passes through and / or in particular at least partially embedded in the carrier and / or matrix material; and or in particular wherein the nanoparticles, in particular the carrier and / or matrix material, are delimited and / or compartmentalized by the membrane system, in particular the membrane and / or membrane structure; and or wherein the membrane system, in particular the membrane and / or membrane structure, at least partially, preferably at least substantially completely, is formed by the dispersant; and or wherein the membrane system, in particular the membrane and / or membrane structure, is formed as a monomolecular layer or as a bimolecular layer, preferably as a monomolecular layer. Nanoparticles according to claim 1 or 2, wherein the dispersant is selected from surface-active and / or amphiphilic substances and / or surfactants, in particular from the group of (i) cationic surfactants, in particular quaternary ammonium compounds, preferably alkyltrimethylammonium salts, preferably cetrimonium bromide (cetyltrimethylammonium bromide), dialkyldimethylammonium salts or Benzalkonium salts, especially cetylpyridinium chloride; (ii) anionic surfactants, especially alkylbenzenesulfonates or fatty alcohol sulfates; (iii) nonionic surfactants, in particular polyalkylene glycol ethers, preferably ethers based on polyethylene glycols and fatty alcohols, alkyl glucosides, alkyl polyglucosides or nonylphenol ethoxylates; (iv) amphoteric surfactants, especially betaines, preferably cocamidopropylbetaine, or sultaines; and (v) their mixtures and combinations; and / or wherein the dispersing agent is selected from surface-active substances, in particular natural and / or nature-identical surfactants and / or surfactants of natural origin, preferably from the group of physiological bile acids, in particular sodium cholate, sodium dehydrocholate, sodium deoxycholate or sodium taurocholate; Phospholipids, in particular lecithins; and their mixtures and combinations; and / or wherein the nanoparticles contain the dispersing agent in an amount in the range from 0.1 to 20% by weight, in particular in the range from 0.5 to 15% by weight, preferably in the range from 1 to 10% by weight, preferably in the range from 2 to 8% by weight, based on the nanoparticles; and / or wherein the carrier and / or matrix material is selected from waxes, lipids and / or polymers, in particular from the group of (i) glycerides and / or glycerol esters, in particular di- or triglycerides and / or glycerol or glycerol triesters, preferably Di- or triglycerides and / or glycerol or glycerol triesters of straight-chain saturated fatty acids having 8 to 30 carbon atoms, preferably di- or triglycerides and / or glycerol or glycerol triesters of caprylic acid, capric acid, undecanoic acid, lauric acid, palmitic acid, stearic acid and / or arachidic acid; (Ii) fatty alcohols or their esters with fatty acids, in particular straight-chain saturated fatty alcohols having 6 to 30 carbon atoms, preferably having 8 to 22 carbon atoms, preferably lauryl alcohol, cetyl alcohol, stearyl alcohol, lignoceryl alcohol or myristyl alcohol; (iii) fatty acids or their esters with fatty alcohols, preferably straight-chain saturated fatty acids having 8 to 30 carbon atoms, preferably caprylic, capric, undecanoic, lauric, palmitic, stearic or arachidic acid; (iv) triterpenes, especially squalene or squalane; (v) natural or synthetic waxes, in particular vegetable waxes, animal waxes, mineral waxes or petrochemical waxes, preferably beeswax, wool wax, carnauba wax, candelilla wax, cetyl palmitate, waxes based on glycerol trifatty acid esters, paraffin waxes or rice wax; and (vi) their mixtures and combinations; and / or wherein the nanoparticles contain the carrier and / or matrix material in an amount in the range from 5 to 99% by weight, in particular in the range from 10 to 95% by weight, preferably in the range from 15 to 90% by weight. , preferably in the range from 20 to 85% by weight, particularly preferably in the range from 25 to 80% by weight, based on the nanoparticles; and / or wherein the nanoparticles comprise the at least one carrier and / or matrix material and the at least one dispersant in a weight-related quantitative ratio of carrier and / or matrix material to dispersant (carrier and / or matrix material: dispersant) in the range from 1: 100 to 100: 1, in particular in the range of 1:20 to 20: 1, preferably in the range of 1:10 to 10: 1, preferably in the range of 1: 5 to 5: 1, have. Nanoparticles according to one of the preceding claims, wherein (a) the first active ingredient is selected from the group of (i) vegetable oils, in particular essential oils; (ii) antibacterial and / or antimicrobial agents; and (iii) their mixtures and combinations; in particular wherein (i) the vegetable oils, in particular the essential oils, are selected from the group of mint oil, in particular peppermint oil, eucalyptus oil, thyme oil, clove oil, citronella oil, chamomile oil, orange oil, rosemary oil, lemon oil, sage oil, wintergreen oil and mixtures thereof or combinations thereof, preferably peppermint oil and wintergreen oil; and / or in particular wherein (ii) the antibacterial and / or antimicrobial active substances are selected from the group of pharmaceutically usable antiseptics, in particular triclosan, cetylpyridinium chloride, chlorhexamed, chlorhexidine, octenidine, cetrimonium bromide (cetyltrimethylammonium bromide) and mixtures or combinations thereof; and / or wherein the nanoparticles (a) the first active ingredient in an amount in the range of 0.1 to 80 wt .-%, in particular in the range of 0.5 to 75 wt .-%, preferably in the range of 1 to 70 wt .-%, preferably in the range of 5 to 65 wt .-%, based on the nanoparticles contain; and / or wherein (b) the at least one preferably acidic glycosaminoglycan is hyaluronic acid or its physiologically tolerable derivatives or salts, in particular the sodium salt of hyaluronic acid; and / or wherein (b) the at least one preferably acid glycosaminoglycan and / or its physiologically tolerated derivatives or salts, in particular hyaluronic acid and / or physiologically acceptable derivatives or salts thereof, have a molecular weight, in particular a number average molecular weight, in the range from 10,000 to 3,000 .000 Da, in particular in the range of 15,000 to 2,500,000 Da, preferably in the range of 20,000 to 2,000,000 Da, preferably in the range of 50,000 to 1,500,000 Da; and / or wherein (b) the nanoparticles comprise the at least one preferably acid glycosaminoglycan or its physiologically tolerated derivatives or salts, in particular hyaluronic acid or its physiologically tolerated salts, in an amount in the range from 0.01 to 10% by weight, in particular Range from 0.1 to 8 wt .-%, preferably in the range of 0.5 to 5 wt .-%, preferably in the range of 1 to 4 wt .-%, based on the nanoparticles contain; and / or wherein (b) the second active ingredient in the form of the at least one preferably acidic glycosaminoglycan or its physiologically tolerable derivatives or salts, in particular the hyaluronic acid or its physiologically tolerable salts, incorporated into the nanoparticles and / or attached to the nanoparticles and / or is superimposed and / or wherein (b) the second active ingredient in the form of at least one preferably acidic glycosaminoglycan or its physiologically acceptable derivatives or salts, in particular the hyaluronic acid or its physiologically acceptable salts, on the upper and / or boundary surface of the nanoparticles and / or is stored; and / or wherein the nanoparticles (c) have at least one auxiliary and / or ingredient, in particular wherein (c) the auxiliary and / or ingredient is selected from the group of (i) flavorings and / or flavoring agents, in particular natural or nature-identical Flavors or flavoring agents; (ii) vitamins and / or their precursors and / or precursors; and (iii) their mixtures and combinations; in particular wherein (i) the flavors or flavoring agents are selected from phytochemicals, in particular from the group of phenolic compounds, in particular simple phenols, polyphenols, xanthones, phenylpropanoids, stilbenes and their glycosides; isoprenoid compounds, in particular terpenes, preferably menthol, cineol or menthone; alkaloids; and their mixtures or combinations; and / or in particular wherein (ii) the vitamins or their precursors or precursors are selected from the group of fat-soluble vitamins or their precursors or precursors, in particular vitamin A, preferably in the form of retinol; Vitamin D; Vitamin E, preferably in the form of alpha tocopherol; Vitamin K; and their mixtures or combinations; and / or in particular wherein the nanoparticles (c) the auxiliary and / or ingredient in an amount in the range of 0.01 to 60 wt .-%, in particular in the range of 0.1 to 50 wt .-%, preferably in the range from 0.5 to 40% by weight, preferably in the range from 1 to 30% by weight, based on the nanoparticles. Nanoparticles according to one of the preceding claims, wherein the nanoparticles under storage and / or use conditions has an average particle diameter, in particular an average particle diameter D50, in the range of 8 to 12,000 nm, in particular in the range of 20 to 10,000 nm, preferably in the range of 50 to 8,000 nm, preferably in the range of 75 to 5,000 nm, more preferably in the range of 150 to 2,500 nm have; and or wherein the nanoparticles are under storage and / or application conditions at least substantially spherical and / or stretched and / or teardrop-shaped, in particular at least substantially spherical and / or teardrop-shaped, preferably at least substantially spherical, are formed; and or wherein the nanoparticles comprise at least one additive, in particular selected from the group of processing aids, colorants, buffers, fragrances, fragrances, extenders, binders, wetting agents and / or preservatives, pH adjusters, pH buffer substances, thickeners, Flavorings, flavorings, sweeteners and sweeteners, acidulants, stabilizers and / or antiseptics and mixtures thereof. Nanoparticles according to one of the preceding claims, wherein the nanoparticles, in particular for application and / or administration to the human and / or animal body, are present in a solid and / or at least substantially liquid-free application and / or dosage form; in particular wherein the nanoparticles are incorporated in dragees, tablets, compactates or the like or are present as dragees, tablets, compactates or the like; and or in particular wherein the dragees, tablets, compacts or the like are obtainable by pressing a plurality of nanoparticles; and or in particular wherein the nanoparticles are incorporated and / or incorporated in a carrier substance, preferably based on sugars, sugar substitutes and / or sweeteners; and or in particular wherein the nanoparticles are introduced into a pharmaceutically usable capsule material, in particular a capsule shell, preferably based on gelatin. Nanoparticle according to one of the preceding claims, wherein the nanoparticles, in particular for application and / or administration to the human and / or animal body, are in liquid administration and / or dosage form, in particular wherein the nanoparticles are present as a dispersion, preferably by introduction into at least one Dissolving and / or dispersing agent, in particular wherein the dispersion is aqueous, organic or aqueous-organic. Active substance-containing nanoparticles, in particular according to one of the preceding claims, obtainable by a process comprising the following steps: (a) providing a first, in particular organic phase, wherein the first phase comprises at least one carrier and / or matrix material; at least one dispersant; and (a) at least one topically applied first active ingredient; (b) providing a second, in particular aqueous phase, wherein the second phase comprises at least one dispersant, in particular water; (B) at least one second active ingredient in the form of a preferably acid glycosaminoglycan or its physiologically acceptable derivatives or salts; optionally a liquid which is miscible with the dispersing agent, in particular water, in particular at least one polyalkylene glycol, preferably polyethylene glycol, and / or at least one polyhydric alcohol, preferably glycerol; (C) mixing and / or mixing, in particular by means of stirring, the first, in particular organic phase with the second, in particular aqueous phase, with heating to a temperature above the Melting and / or softening point of the carrier and / or matrix material, in particular with formation of a liquid-crystalline phase, in particular of the carrier and / or matrix material; (d) cooling the mixture obtained in step (c), in particular with stirring, below the melting and / or softening point of the carrier and / or matrix material to obtain the active ingredient-containing nanoparticles present in a dispersion; and (e) optionally removing the liquid components and / or constituents, in particular water, preferably by means of drying, preferably by freeze-drying, to obtain the dried and / or isolated active ingredient-containing nanoparticles. Nanoparticles according to one of the preceding claims for use in prophylactic and / or curative treatment, in particular topical treatment, the oral and / or pharyngeal mucosa and / or the oral cavity; and or for use in prophylactic and / or curative treatment, in particular topical treatment, of dry mouth, preferably in smokers, and / or hoarseness and / or inflammatory diseases of the oropharynx, especially colds and / or influenza infections, and / or Use in general oral and / or dental care and / or general oral and / or dental hygiene. Use of nanoparticles according to one of the preceding claims for prophylactic and / or curative treatment, in particular topical treatment, the oral and / or pharyngeal mucosa and / or the oral cavity; and or for prophylactic and / or curative treatment, in particular topical treatment, of dry mouth, preferably in smokers, and / or hoarseness and / or inflammatory diseases of the oropharynx, in particular colds and / or influenza infections, and / or in the general mouth - and / or dental care and / or in general oral and / or dental hygiene. Process for the preparation of active substance-containing nanoparticles, in particular for topical application on the oral and / or pharyngeal mucosa and / or in the oral cavity, preferably nanoparticles according to one of Claims 1 to 9, the process comprising the following steps: (A) providing a first, in particular organic phase, wherein the first phase at least one carrier and / or matrix material; at least one dispersant; and (a) at least one topically applied first active ingredient; (b) providing a second, in particular aqueous phase, wherein the second phase comprises at least one dispersant, in particular water; (B) at least one second active ingredient in the form of a preferably acid glycosaminoglycan or its physiologically acceptable derivatives or salts; optionally a liquid which is miscible with the dispersing agent, in particular water, in particular at least one polyalkylene glycol, preferably polyethylene glycol, and / or at least one polyhydric alcohol, preferably glycerol; (C) mixing and / or mixing, in particular by means of stirring, the first, in particular organic phase with the second, especially aqueous phase, with heating to a temperature above the melting and / or softening point of the carrier and / or matrix material, in particular Forming a liquid-crystalline phase in particular of the carrier and / or matrix material; (d) cooling the mixture obtained in step (c), in particular with stirring, below the melting and / or softening point of the carrier and / or matrix material to obtain the active ingredient-containing nanoparticles present in a dispersion. Method according to claim 11, wherein in step (d) optionally at least one further dispersing agent, in particular water, and / or at least one water-miscible liquid, preferably at least one polyalkylene glycol, preferably polyethylene glycol, and / or at least one polyhydric alcohol, preferably glycerol, is used; and or wherein in a further step (e) liquid components and / or constituents, in particular water, are preferably removed by means of drying, preferably by freeze drying, to obtain dried and / or isolated active substance-containing nanoparticles. Dispersion comprising active ingredient-containing nanoparticles, in particular nanoparticles according to one of Claims 1 to 9, preferably for topical application on the oral and / or pharyngeal mucosa and / or in the oral cavity; wherein the nanoparticles have at least one carrier and / or matrix material on the one hand and at least one dispersant on the other hand and wherein the nanoparticles (a) at least one preferably in the Contain carrier and / or matrix material embedded and / or incorporated, in particular topically applied first active ingredient; and wherein the dispersion and / or the nanoparticles (b) contain or contain at least one second active ingredient in the form of a preferably acidic glycosaminoglycan or its physiologically acceptable derivatives or salts. Dispersion according to claim 13, wherein the dispersion is aqueous, organic or aqueous-organic; and or wherein the dispersion is formed as an emulsion or suspension, in particular as an emulsion, preferably as an oil-in-water emulsion; and or wherein the dispersion contains at least one dispersing agent, preferably water, in particular in an amount in the range from 10 to 90% by weight, in particular in the range from 15 to 85% by weight, preferably in the range from 20 to 80% by weight , preferably in the range of 25 to 75 wt .-%, based on the dispersion; and or wherein the dispersion contains at least one further, preferably water-miscible liquid, in particular in an amount in the range of 1 to 80 wt .-%, in particular in the range of 5 to 75 wt .-%, preferably in the range of 10 to 70 wt. %, preferably in the range of 15 to 65 wt .-%, based on the dispersion, in particular wherein the further, preferably water-miscible liquid is selected from water-soluble or water-dispersible polyalkylene glycols, in particular polyethylene glycol, and / or polyhydric alcohols, in particular glycerol; and or wherein the dispersion contains the nanoparticles in a volume-related amount in the range of 1 to 90% by volume, in particular in the range of 5 to 85% by volume, preferably 10 to 80% by volume, particularly preferably 15 to 75% by volume , based on the dispersion contains; and or wherein the dispersion contains the nanoparticles in a mass-based amount in the range of 5 to 80 wt .-%, in particular in the range of 10 to 75 wt .-%, preferably in the range of 15 to 70 wt .-%, based on the dispersion ; and or wherein the dispersion (b) the second active ingredient in the form of at least one preferably acid glycosaminoglycan and / or its physiologically acceptable salts in an amount in the range of 0.01 to 5 wt .-%, in particular in the range of 0.05 to 4 wt .-%, preferably in the range of 0.1 to 3 wt .-%, based on the dispersion contains; and or wherein (b) the second active ingredient is dispersed and / or dissolved in the form of the at least one preferably acidic glycosaminoglycan or its physiologically acceptable derivatives or salts, in the dispersion, in particular the dispersing agent, and / or wherein (b) the second active ingredient is in the form of at least one preferably acidic glycosaminoglycan or its physiologically tolerable derivatives or salts are incorporated into the nanoparticles and / or attached to and / or deposited on the nanoparticles and / or wherein (b) the second active ingredient is in the form of the at least one preferably acidic glycosaminoglycan or its physiological compatible derivatives or salts, to the upper and / or interface of the nanoparticles and / or superimposed; and or wherein the dispersion contains at least one viscosity-increasing agent and / or a thickening agent, in particular wherein the viscosity-increasing agent and / or the thickener is selected from the group of polysaccharides, in particular cellulose, cellulose derivatives or xanthanes, polyalkyl acrylates, polyvinylpyrrolidones, Polyalkylcyanacrylaten, acrylic polymers, polylactates, polylactides , Bentonites, silicic acids, carbomers and mixtures thereof, in particular wherein the dispersion contains the viscosity-increasing agent and / or the thickener in an amount in the range from 0.01 to 20% by weight, in particular in the range from 0.1 to 10% by weight. , preferably in the range 0.5 to 5 wt .-%, preferably in the range of 1 to 3 wt .-%, based on the dispersion contains; and or wherein the dispersion under storage and / or use conditions, in particular at 25 ° C, a Brookfield viscosity in the range of 500 to 100,000 mPas, in particular in the range of 1,000 to 90,000 mPas, preferably in the range of 2,000 to 80,000 mPas, preferably in the range from 2,500 to 70,000 mPas; and or wherein the dispersion contains at least one acid and / or base, in particular for forming a buffer system; and or wherein the dispersion contains at least one buffer system, in particular wherein the buffer system is selected from the group of carbonate buffers, citrate buffers or phosphate buffers, in particular phosphate buffers; and or wherein the dispersion comprises at least one additive, in particular selected from the group of processing aids, colorants, buffers, fragrances, fragrances, extenders, binders, wetting agents and / or preservatives, pH adjusters, pH buffer substances, thickeners, Flavorings, flavorings, sweeteners and sweeteners, acidulants, stabilizers and / or antiseptics and mixtures thereof. A dispersion according to claim 13 or 14, wherein the dispersion is in the form of a liquid administration and / or dosage form; and / or wherein the dispersion is in the form of a fluid, mouthwash, mouthwash, juice, gargle solution or the like. Dispersion according to claim 13 or 14, wherein the dispersion is present as pasty and / or semi-solid application and / or dosage form; and or wherein the dispersion is in the form of a cream, ointment, lotion or the like. Dispersion according to claim 13 or 14, wherein the dispersion is present as an aerosol-like application and / or dosage form; and or wherein the dispersion is in the form of a spray, spray composition or the like. Dispersion according to one of claims 13 to 17 for use in prophylactic and / or curative treatment, in particular topical treatment, the oral and / or pharyngeal mucosa and / or the oral cavity; and or for use in prophylactic and / or curative treatment, in particular topical treatment, of dry mouth, preferably in smokers, and / or hoarseness and / or inflammatory diseases of the oropharynx, especially colds and / or influenza infections, and / or Use in general oral and / or dental care and / or general oral and / or dental hygiene. Use of a dispersion according to any of claims 13 to 17 for prophylactic and / or curative treatment, in particular topical treatment, the oral and / or pharyngeal mucosa and / or the oral cavity; and or for prophylactic and / or curative treatment, in particular topical treatment, of dry mouth, preferably in smokers, and / or hoarseness and / or inflammatory diseases of the oropharynx, especially colds and / or influenza, and / or use in the general Oral and / or dental care and / or in general oral and / or dental hygiene. Dosage and / or administration form, in particular in solid, liquid, pasty or aerosol-like form, containing active ingredient-containing nanoparticles according to one of claims 1 to 9. Dosage and / or administration form, in particular in liquid, pasty or aerosol form, containing a dispersion according to one of claims 13 to 17.