EP1139994A1

EP1139994A1 - Oral hygiene product containing spherical microparticles on the basis of linear water-insoluble polyglucans

Info

Publication number: EP1139994A1
Application number: EP99962187A
Authority: EP
Inventors: Holger Bengs; Silke Schuth; Jürgen Grande; Gitte Böhm
Original assignee: Celanese Ventures GmbH
Current assignee: Celanese Ventures GmbH
Priority date: 1998-12-28
Filing date: 1999-11-30
Publication date: 2001-10-10
Also published as: JP2002533374A; DE19860373A1; AU1860900A; DE19860373B4; WO2000038643A1

Abstract

The present invention relates to oral hygiene products containing spherical microparticles as the essential component. Said microparticles consist entirely or partially of at least one water-insoluble linear polyglucan.

Description

Oral care products containing spherical microparticles based on linear water-insoluble polygiucans

description

The present invention relates to an oral care product which contains spherical microparticles based on linear water-insoluble polygiucans as an essential component.

The use of polyglucans in oral care products, in particular toothpaste and chewing gums for dental hygiene, has long been known.

However, polygiucans are a very heterogeneous class of compounds, the individual

Representatives with a wide variety of properties. A well-known example of polyglucan that is widely used in nature is starch. Starch consists of two different polyglucans, amylose and amylopectin, the proportion of which varies

Origin of starch varies widely.

Amylose is a water-soluble linear 1,4-linked poly-α-glucan with a

Molecular weight of about 50,000 to 150,000, however, amylopectin is water-insoluble and has a highly branched structure with 1, 4 and 1, 6 linkages with a molecular weight of 300,000 to 2,000,000.

Another common polyglucan is Ceiiulose, which is insoluble in water and

Contrary to strength ß-1, 4 is linked.

Starch and its components are used in oral care products as

Gelling agent, filler, thickener or binder used. For example, EP-B-0 502 895 describes a thickener for toothpastes which, in addition to a linear polymeric non-starch compound such as cellulose and its derivatives, for example carboxymethyl or hydroxyethyl cellulose, contains a branched starch. Branched starch here means a starch which consists at least 70% of branched polyglucans and preferably has a molecular weight of 1,000,000 to 2,000,000. It is known to derivatize starch or its polyglucan components in order to achieve certain properties.

For example, US Pat. No. 5,009,882 relates to the use of a carboxylated starch in oral care products such as toothpastes or mouthwashes to prevent plaque formation. The starch molecule described here is composed of non-carboxylated glucan blocks and carboxylated glucan blocks with a degree of carboxylation of 1 to 3, the carboxylation taking place with the ring opening of the glucan unit.

EP-A-0 673 605 proposes a particulate matrix as a carrier for an aroma substance such as lemon oil, with which the storage stability of the aroma substance e.g. in toothpastes and chewing gums for oral hygiene. The matrix consists of a mixture of a hydrogenated starch hydrolyzate and maltodextrose, the hydrolyzed starch hydrolyzate being a polyol with a

Degree of polymerization is at most 4, of which one terminal glucan unit is opened hydrolytically.

Although a large number of different oral care products are already available, the development of new, improved products is of great importance since the most effective protection against caries and periodontosis is careful dental care with suitable products.

For example, tooth cleaning agents such as tooth pastes, tooth powder and chewing gum should be cleaned gently without being abrasive to protect the tooth enamel. This presupposes that these agents do not contain any components that can have an abrasive effect.

A wide variety of active ingredients are often added to mouth care products to improve their nourishing properties. So that these active ingredients can be fully effective, it is advantageous to incorporate them into a suitable matrix that ensures optimal release at the target site.

In general, such funds should also be used over a longer storage period

Maintain consistency and effectiveness. The use of spherical microparticles which consist wholly or partly of at least one water-insoluble linear polyglucan is essential for the oral care products according to the invention.

For the present invention, oral care means both agents that either serve only to clean the oral cavity and are therefore attributable to cosmetics, as well as agents that also have therapeutic purposes due to additional active ingredients with specific preventive and healing properties and are therefore to be regarded as medicinal products.

Examples of oral care products are mouthwashes, mouth powder, mouth pills, mouth sprays, denture, prosthetic and dental care products such as toothpastes, tooth gels, tooth cleaning powder and chewing gum to improve oral hygiene, but also plaque stain tablets to make dental plaque visible, e.g. B. as a control.

The microparticles used in oral care products according to the invention are particularly notable for their multifunctionality and can be used and adapted for a large number of very different applications, so that they can be used to obtain targeted oral care products for a wide variety of uses.

In general, the microparticles can replace the conventional polygiucans previously used in oral care products and take on their function as thickeners, binders, fillers or gelling agents.

They also have an excellent cleaning and polishing effect and are therefore particularly suitable as cleaning and polishing agents, e.g. B. for mechanical tooth, denture and prosthesis cleaning. In addition to their regular spherical shape, the microparticles used according to the invention have very good dispersibility. It has been shown that they can also be used without the addition of other aids

Dispersing aids can form a stable dispersion that remains stable even over a long period of time.

So you can z. B. form stable emulsions, aerosols or suspensions.

This property is of particular importance for the production of suitable formulations for oral care products, since it is often possible to dispense with the addition of dispersing auxiliaries or the amount of dispersing auxiliaries can be reduced, as a result of which the production can be simplified and cheaper.

Of particular importance for dental hygiene are toothpastes, in transparent form called gel, which optimize the plaque-removing effect of toothbrushes due to their content of cleaning and polishing bodies as well as surface-active substances and, if necessary, apply active ingredients such as fluorides to protect the tooth and tooth-holding apparatus.

Because of their uniform spherical shape with no or only slight surface roughness without large irregularities such as projections, corners or edges, the microparticles used according to the invention do not have an abrasive effect and can therefore be used advantageously in dental care products.

In addition, the microparticles are an excellent carrier material for active ingredients such as healing or nourishing substances, flavorings, etc.

For this purpose, the active ingredient can be added to the starting compounds used for the production of the microparticles, so that the microparticles are present from a mixture of starting compound and active ingredient.

The active ingredient can be encapsulated in the microparticles, the usual ones

Encapsulation techniques can be used. Suitable examples are emulsion processes or spray drying processes. The last term also includes spray processes in which the particles are sprayed with a solution of the active ingredient in a fluidized bed or in an analogous process. Furthermore, the active ingredient can be absorbed and / or adsorbed on the microparticle surface by z. B. the active ingredient and the microparticles suspended in a suitable medium, allowed to stand until equilibrium is reached and then the particles loaded with active ingredient are separated.

If necessary, the microparticles used according to the invention can be designed for the controlled release of active substance.

Controlled release of active substance is understood to mean that the active substance is not released immediately and all at once, but that the release takes place via a certain one

Period and / or after a certain period of time. The release rate can be chosen arbitrarily depending on the intended use. It can be constant over time, or it can be large initially, followed by slow release. Controlled release of active ingredient can e.g. B. advantageous for dentition and

Prosthesis cleaning agents that act on the denture or prosthesis for a longer period of time, for chewing gum to achieve a uniform effect and long-lasting taste, or for targeted local administration in the oral cavity, throat, teeth, etc., the can also be summarized under the terms "mucosal" or "buccal" applications, for example also in the form of so-called drug delivery systems.

It goes without saying that the rate of release and the rate of degradation of the microparticles strongly depend on the type of starting materials of the active ingredient used, the particle size and the production process.

Depending on requirements, the person skilled in the art can create a system which is tailor-made for his specific purpose by simply routine variations of these parameters.

A detailed description of the use of those used according to the invention

Microparticles as agents for the controlled release of active substances are the unpublished German application of the applicant with the official file number 198 16 070.4 “prolonged-release tablet, made from linear water-insoluble polysaccharides ", to which express reference is made here in this connection.

Because of their good dispersibility and suitability as a carrier material, mouth sprays can advantageously be applied to the microparticles used according to the invention

Aerosol base can be obtained.

Spherical microparticles are to be understood as microparticles which have approximately spherical shape. When a sphere is described by axes of the same length that start from a common origin and are directed into space

Define the radius of the sphere in all spatial directions, the spherical particles can deviate from the ideal length of the sphere by 1% to 40%. The deviation is preferably 25% or less, particularly preferably 15% or less.

The microparticles can have an average diameter Dn (number average) of 1 nm to 100 μm, preferably 100 nm to 15 μm, and particularly preferably 300 nm to 3 μm.

It goes without saying that the average diameter can vary depending on the type of oral care product.

Small microparticles with an average diameter of 15 μm or less are particularly suitable for use in oral care products.

The surface of the spherical particles can be compared macroscopically with a raspberry, the depth of irregularities on the particle surface, such as indentations or cuts, being a maximum of 20%, preferably 10%, of the mean diameter of the spherical microparticles.

The specific surface area of the microparticles is in general from 1 m ² / g to 100 m ² / g, preferably 1.5 m ² / g to 20 m ² / g and particularly preferably 3 m / g to 10 m ² / g. Furthermore, the particles used according to the invention preferably show one

Dispersity D = weight average of the diameter (d _w ) / number average of the

Diameter (d _n ) from 1.0 to 10.0, in particular from 1.5 to 5.0 and particularly preferably from 2.0 to 3.0.

The mean values used here are defined as follows:

d _n = sum n _j xd _j / sum n _j = number mean d _w = sum n _j xd _j ² / sum n _j xd _j = weight mean n _f = number of particles with diameter d _j , d _j = a certain diameter, i = continuous parameter.

In this context, the term weight means a weighted average, which means that the larger diameters are more important.

Microparticles whose surface has been modified can also be used for the present invention, for example by derivatization of functional groups such as the hydroxyl groups of the starting polyglucan compound.

Linear water-insoluble polygiucans for the purposes of the present invention are polysaccharides which are composed of glucans as monomeric building blocks in such a way that the individual building blocks are always linked to one another in the same way. Each basic unit or building block defined in this way has exactly two links, one each to a different monomer. The only exception are the two basic units that form the beginning and the end of the polysaccharide. These have only one link to another monomer and form the end groups of the linear polyglucan.

If the basic unit has three or more links, this is referred to as branching. The number of hydroxyl groups per 100 results Basic units that are not involved in the construction of the linear polymer backbone and form the branches, the so-called degree of branching.

According to the invention, the linear water-insoluble polygiucans have a degree of branching of at most 8%, i.e. they have a maximum of 8 branches per 100 basic units. The degree of branching is preferably less than 4% and in particular a maximum of 2.5%.

Particularly preferred are polygiucans whose degree of branching in the 6-position is less than 4%, preferably at most 2% and in particular at most 0.5%, and in the other positions, e.g. B. in 2- or 3-position, preferably at most 2

% and in particular 1%.

Polygiucans with a branching in the 6-position of less than 0.5% are also particularly preferred. Polygiucans which are not suitable are particularly suitable for the invention

Have branches, or the degree of branching is so minimal that it can no longer be detected using conventional methods

Examples of preferred water-insoluble linear polygiucans are linear poly-D-glucans, the type of linkage being immaterial as long as there is linearity in the sense of the invention. Examples are poly-alpha-D-glucans, in particular poly (1,4-alpha-D-glucan), and poly (1,3-beta-D-glucans)

For the present invention, the prefixes "alpha", "beta" or "D" refer solely to the linkages that form the polymer backbone and not to the

Ramifications.

For the present invention, the term “water-insoluble polyglucan” is understood to mean compounds which, according to the definition of the German Medicinal Products Book (DAB = German Medicinal Products Book, Scientific

Verlagsgesellschaft mbH, Stuttgart, Govi-Verlag, Frankfurt, edition, 1987) fall into the categories "poorly soluble", "poorly soluble", "very poorly soluble" or "practically insoluble" compounds according to classes 4 to 7. In the case of the polygiucans used according to the invention, this means that at least 98% of the amount used, in particular at least 99.5%, below

Normal conditions (T = 25 ° C +/- 20%, p = 101325 Pascal +/- 20%) is insoluble in water (according to classes 4 and 5).

For the present invention, sparingly soluble to practically insoluble are

Compounds, especially very poorly soluble to practically insoluble

Compounds, preferred.

"Very poorly soluble" according to class 6 can be achieved by the following

Test description can be illustrated:

One gram of the polyglucan to be examined is heated in 1 l of deionized water to 130 ° C. under a pressure of 1 bar. The resulting solution only remains stable for a short time over a few minutes. When cooling under normal conditions, the substance precipitates again. After cooling to room temperature and separation by centrifugation, taking into account the experimental losses, at least 66% of the amount used can be recovered.

The polygiucans used according to the invention can be of any origin as long as the conditions given above with regard to the terms "linear" and "water-insoluble" are met. They can be obtained naturally or by biotechnological means.

For example, they can be obtained from natural plant or animal sources by isolation and / or purification.

Sources can also be used which have been genetically manipulated in such a way that they contain a higher proportion of non-or comparatively slightly branched polyglucans compared to the unmanipulated source.

They can also have been produced from nonlinear polyglucans by enzymatic or chemical branching. Non-linear polygiucans which contain branches can be treated with an enzyme in such a way that the branches are split, so that linear polygiucans are present after their separation. These enzymes can be, for example, amylases, isoamylases, gluconohydrolases, cyclomaltodextrin glucanotransferases or pullulanases.

Biotechnical methods include biocatalytic, also biotransformatory, or fermentative processes.

Linear polygiucans produced by biocatalysis (also: biotransformation) in the

Within the scope of this invention, the linear polyglucan is obtained by catalytic reaction of monomeric building blocks such as oligomeric saccharides, e.g. of mono- and / or disaccharides, is produced by using a so-called biocatalyst, usually an enzyme, under suitable conditions. In this context one speaks of "in vitro biocatalysis".

Linerar polygiucans from fermentations are, in the parlance of the invention, linear polygiucans which are obtained by fermentative processes using organisms which occur in nature, such as fungi, algae, bacilli, bacteria or protists, or which do not occur in nature

Organisms, but modified with the help of genetic engineering methods of general definition, modified natural organisms, such as fungi, algae, bacilli, bacteria or protists, or can be obtained with the help of fermentative processes. In this context, one also speaks of “in vivo biocatalysis”.

Examples of such microorganisms are Piichia pastoris, Trichoderma Reseii, Straphylokkus Camosus, Escherichia Coli or Aspergillus Niger.

Advantageous methods for biotechnological extraction are e.g. B. in the WO

95/31553 or the unpublished German patent application by the applicant with official file number 198 27 978.5. According to WO 95/31553, amylosucrases are used for the production of linear water-insoluble polyglucans such as poly-1, 4-α-D-glucan by means of a biocatalytic process.

Other suitable enzymes are polysaccharide synthases, starch synthases, glycol transferases, 1, 4-α-D-glucan transferases, glycogen synthases or else

Phosphorylases.

Modified water-insoluble linear polygiucans can also be used, the polygiucans not participating in the linear linkage, for example, by esterification and / or etherification in one or more

Positions may have been chemically modified. In the case of the preferred 1,4 linked polygiucans, the modification can take place in the 2-, 3- and / or 6-position.

Modification in the sense of the invention means that the existing

Hydroxyl groups that are not involved in the linkage are chemically changed. This precludes ring opening of the glucan units as e.g. in the oxidative carboxylation or hydrolysis. Measures for such modifications are well known to the person skilled in the art. Linear polygiucans like Pulluiane, which are water-soluble per se, can

Modification can be made water-insoluble.

For the present invention, water-insoluble linear polygiucans are preferably used which have been produced in a biotechnical, in particular in a biocatalytic or a fermentative, process, with biocatalytically produced polyglucan being particularly preferred.

In contrast to polyglucans, which are isolated from natural sources, such as plants, the linear water-insoluble polygiucans obtained in this way have a particularly homogeneous profile of properties, e.g. B. in relation to the

Molecular weight distribution, they contain no or at most only in very small amounts of unwanted by-products that have to be separated in a complex manner or could trigger allergenic reactions, and can be reproduced exactly and easily.

Comparatively homogeneous products can also be obtained with chemical or enzymatic branching. However, remains in many

Cases, a residue of raw material that has not been or has not been adequately debranched and is difficult to separate.

Biotechnical and especially biocatalytic methods have the advantage that directly water-insoluble linear polygiucans can be obtained, such as. B. the preferred poly-1, 4-α-D-glucans, which contain no branches, or whose degree of branching is below the detection limit of conventional analytical methods.

The polygiucans can also be more resistant in the form of so-called alpha-amylase

Polygiucans are used as they are described using the example of poly-1, 4-α-D-glucan in the not previously published German patent application with official file number 198 30 618.0 of the applicant.

Alpha-amylase-resistant polygiucans can be prepared by preparing a suspension or dispersion of water-insoluble polyglucans and water, heating the suspension or dispersion to a temperature in the range from 50 to 100 ° C, and allowing the resulting paste-like mixture to cool to a temperature in the range from 50 ° C to the freezing point, preferably 35 to 15 ° C, 27 to 22 ° C, 16 to 0 ° C or 6 to 2 ° C, over a period of 1 to 72 h, preferably 1 to

36 h and in particular 15 to 30 h and retrogradation of the paste-like mixture at a temperature lower than the temperature of the heated paste-like mixture in a temperature range of 90 to 4 ° C. and optionally drying or dewatering of the product obtained.

The polyglucan can also be used as a thermoplastic polyglucan, which is obtainable by melting linear water-insoluble polyglucan and Adding at least 20% by weight, preferably at least 30% by weight, of one

Plasticizers such as sorbitol, glycerin, their condensation products and oligomers,

DMSO, succinic acid, citric acid monohydrate, malic acid, tartaric acid etc. at approx. 170 ° C. A description of suitable measures and properties of thermoplastic polyglucans using the example of the preferred linear water-insoluble poly (1,4-α-D-glucan) is given by the unpublished German

Patent application of the applicant with official file number 198 30 618.0, to which express reference is made for this. The molecular weights M _w (weight average, determined by means of

Gel permeation chromatography in comparison to a calibration using pullulin standard) of the linear polygiucans used according to the invention can vary within a wide range from 0.75 x 10 ² g / mol to 10 ⁷ g / mol. The molecular weight M _w is preferably in a range from 10 ³ g / mol to 10 ⁶ g / mol and particularly preferably from 10 ³ g / mol to 10 ⁵ g / mol. Another advantageous range is from 2 x 10 ³ to 8 x 10 ³ . Corresponding ranges apply to the preferred poly-1, 4-D-glucan.

The molecular weight distribution or polydispersity M _w / M _n can also vary widely depending on the manufacturing process of the polyglucan. Preferred

Values are from 1.01 to 50, especially from 1.01 to 15, with small polydispersity values being particularly preferred, e.g. from 1.01 to 2.5. The polydispersity increases with a bimodal distribution of the molecular weights.

A single polyglucan, in particular, can be used to produce the microparticles

Poly-1, 4-D-glucan and very particularly poly-1, 4-α-D-glucan or mixtures of two or more representatives can be used.

In a further embodiment, a water-insoluble branched polysaccharide, preferably a polyglucan, in particular a poly-1, 4-alpha-D-glucan, or a poly-1, 3-beta-D-glucan can be added. Mixtures of two or more branched polysaccharides can also be added. The branched polysaccharides can be of any origin. In this

Reference is made to the relevant explanations for the linear water-insoluble polygiucans. Preferred sources are starch and

Starch analogues such as glycogen. If necessary, the proportion of linear structures in the branched polysaccharides can be determined by suitable ones

Enrichment procedures are increased.

The same information applies to water insolubility as for linear water-insoluble polyglucan. The molecular weight may also be higher for the branched polysaccharides, e.g. B. values up to preferably 10 ⁹ g / mol and more.

Other polymers, in particular biocompatible or biodegradable polymers, can also be added. The amount of the other polymer (s) that are added without changing the spherical shape and / or other properties of the microparticles to be produced always depends on the polymer added.

To ensure the desired properties of the microparticles, the proportion of linear water-insoluble polyglucan should be at least 70% by weight, in particular 80

% By weight and preferably 90% by weight, based on the total content of linear water-insoluble polyglucan, including optionally branched polysaccharide and optionally further polymers.

According to a particularly preferred embodiment, the microparticles consist of 100% by weight of linear water-insoluble polyglucan, in particular linear water-insoluble poly-1, 4-α-D-glucan, which has preferably been obtained biocatalytically.

Examples of processes for producing the microparticles are the precipitation process or

Spray drying process. The spherical microparticles can be prepared by dissolving the water-insoluble linear polyglucan or a mixture of several of these and, if appropriate, further polymers in a solvent, for. B. DMSO,

Introducing the solution into a precipitant, e.g. B. water, preferably at a

Temperature from 20 ° C to 60 ° C, if necessary cooling the solution to a temperature of minus 10 ° C to plus 10 ° C and separating the particles formed.

The process of dissolving the polygucan used as the starting material can take place at room temperature or higher temperatures.

The concentration of linear water-insoluble polyglucan including branched polysaccharide and other polymers in the solvent can vary within wide limits as required. It is preferably in a range from 0.02 g / ml to 1.0 g / ml, in particular from 0.05 g / ml to 0.8 g / ml and particularly preferably from 0.3 g / l to 0.6 g / l.

Examples of precipitants are water, dichloromethane, a mixture of water and dichloromethane, mixtures of water and alcohols such as methanol, ethanol, isopropanol, water and a mixture of water and dichloromethane being particularly preferred.

The ratio of solvent to precipitant is preferably selected in a range from 1: 1000 to 1: 4 (part solvent / part precipitant), preferably 1: 100 to 1:10 and in particular 1:70 to 1.30.

In general, the order in which the solvent and the precipitant are brought together is irrelevant, e.g. whether the precipitant is added to the solvent or vice versa. However, it is important that rapid mixing is ensured.

The precipitation process can be carried out relatively slowly at low temperature overnight.

It can be influenced and controlled by varying the temperature and the precipitant. If cooling, ensure that the mixture of solvent and

Means of payment remains liquid and does not solidify.

By using suitable additives, the properties of the microparticles such as size, surface structure, porosity, etc., as well as the

Litigation influence.

Suitable additives are e.g. B. surfactants such as sodium dodecyl sulfate, N-methylgluconamide, polysorbates (e.g. Tween (registered trademark)), alkyl polyglycol ethers, ethylene oxide-propylene oxide block polymers (e.g. Pluronic (registered trademark)), alkyl polyglycol ether sulfates, generally alkyl sulfates and

Fatty acid glycol esters, and sugars such as e.g. B. fructose, sucrose, glucose, water-soluble Ceiiulose or hot water-soluble poly-alpha-D-glucan such as. B. native or chemically modified starches, poly-alpha-D-glucans obtained from these starches and starch-analogous compounds.

These additives are usually added to the precipitant. The amount used depends on the individual case and the desired particle properties, the determination of the respectively advantageous amount being familiar to the person skilled in the art.

By adding water-soluble cellulose derivatives to the precipitant, it is possible to obtain microparticles with a particularly smooth surface, the depth of the irregularities on the surface of the microparticles generally not exceeding 10% of the mean diameter.

Examples of water-soluble cellulose derivatives are cellulose esters and cellulose ethers, their mixed forms such as e.g. Hydroxypropylmethyl celluloses, hydroxyethyl celluloses, carboxymethyl celluloses, cellulose acetates, cellulose butyrates, cellulose propionates, cellulose acetobutyrates, cellulose acetopropionates, cellulose nitrates, ethyl celluloses, benzyl celluloses,

Methyl celluloses etc.

Mixtures of various water-soluble cellulose derivatives can also be used. Under the term "water-soluble cellulose derivatives" for the present

Invention understood compounds according to the definition of German

Drug Book (DAB = German Drug Book, Scientific

Verlagsgesellschaft mbH, Stuttgart, Govi-Verlag GmbH, Frankfurt, 9th edition, 1987) fall under the category very easily soluble to hardly soluble.

The concentration of the water-soluble cellulose derivative in the precipitant is no longer critical. The upper limit inevitably results from the resulting viscosity and thus the processability of the resulting solution.

Concentrations of 2 g (cellulose derivative) / l (precipitant) to 150 g / l, preferably from 5 g / l to 80 g / l and in particular 8 g / l to 20 g / l, have proven to be advantageous. The proportion of particularly small particles with an average diameter of 1 nm to 2 μm can be increased by adding hot water-soluble poly-alpha-D-glucan to the precipitant.

The same poly-alpha-D-glucan compounds can be used for this as they have also been mentioned in connection with the linear water-insoluble polyglucan, insofar as they fulfill the feature that is soluble in hot water.

Preferred examples are native or chemically modified starches, poly-alpha-D-glucans obtained from these starches and starch-analogous compounds.

Starch-analogous compounds are understood to mean compounds which consist of poly-alpha-D-glucans but are of non-vegetable origin. On

An example of this is glycogen or dextran.

The hot water-soluble poly-alpha-D-glucans can be used as a mixture of a linear and a branched portion, such as is present in starch. In this case, the proportion of linear poly-alpha-D-glucan should be more than 15% by weight, preferably 50 to 99.5% by weight, in particular 60 to 90% by weight and very particularly preferably 65 to 80% by weight, based on the total amount of poly-alpha-D-glucan in the precipitant. But they can also consist of branched structures, such as those in

Amylopectin or in glycogen.

In the context of the present invention, “hot water-soluble” means that the poly-alpha-D-glucans are essentially insoluble at room temperature, preferably the same scale as for the term “water-insoluble” in connection with linear polysaccharides.

The term “solution” or “solubility” is understood in particular to also mean suspensions or the formation of suspensions as described in the

Solution of starch occur.

For example, the hot water-soluble starches preferred according to the invention show virtually no solubility in water at room temperature, while the so-called cold water-soluble starches are more readily soluble under these conditions.

The hot water-soluble starches are characterized in particular by the fact that when heated under their own pressure, e.g. in an autoclave, to a temperature in the range of about 100 to about 160 ° C, where the respective

Temperature depends on the type of starch.

For example, potato starch can be cooked at around 100 ° C until completely dissolved, while corn starch requires a temperature of around 125 ° C.

For the process according to the invention, the hot water-soluble poly-alpha-D-glucans are preferably added to the precipitant in maximum concentration, i.e. a saturated solution is prepared. Further suitable ranges are from more than 0.001% by weight to 10% by weight, preferably from 0.01 to 2% by weight and in particular from 0.05% by weight to 0.5% by weight, based on the amount used Precipitant.

In the case of thermoplastic polyglucans, the additives can advantageously be used as plasticizers or in addition to the plasticizers thermoplastic mixture are mixed so that a dry

Powder mixture is present, which can then be processed into the microparticles, the microparticle formation process also being able to take place only in the final recipe, with the thermoplastic polygiucans mixed in.

A detailed description of the microparticles used here, their production and the water-insoluble linear polygiucans that can be used for them can be found in the older, unpublished German patent applications of the

Applicant with file number 197 37481.6, 198 03 415.6, 198 16 070.4, 198 30 618.0, 198 27 978.7, 198 39 216.8, 198 39 214.1 and 198 39 212.5 to which reference is made for the present description.

Furthermore, the microparticles used according to the invention are distinguished by high biocompatibility. For the biocompatibility of the microparticles used according to the invention, the nature-identical character of the water-insoluble linear polygiucans used for the preparation and of their degradation products is of particular importance.

Unless stated otherwise, the percentages by weight for the composition of the oral care products relate to the total weight of the

Mouth care product.

The oral care products according to the invention can, depending on the type and field of application, up to 90% by weight, in particular up to 70% by weight, preferably 2% by weight to 50% by weight, in particular 15% by weight to 45% by weight and particularly preferably 20% by weight to 25% by weight of microparticles, based on the total composition.

The composition of the oral care products according to the invention is explained in more detail below.

The frame structure of a toothpaste essentially contains 15-60% by weight of cleaning material, up to 40% by weight of humectant, which should prevent drying out, and up to approx. 2% by weight of binder, which determine the viscosity and creamy consistency of the strand. up to approx. 0.2% by weight of preservative to prevent the bacterial decomposition, in particular of binders and humectants, up to approx. 2.0% by weight of surfactants, and further additives, such as sweeteners (up to approx. 0.1% by weight) to improve taste, flavoring agents (up to approx. 1% by weight). -%) and special active ingredients.

Tooth powders differ from toothpastes primarily in that they do not contain any humectants, but their percentage of cleaning agents can be up to 90% by weight.

Examples of cleaning bodies which can be used in addition to the microparticles according to the invention are aluminum hydroxide, calcium carbonate, calcium hydrogenphosphate dihydrate, calcium hydrogenphosphate, silicic acid, sodium aluminum silicates with, for example, zeolite structure (Na-ι ₂ (AI0 ₂ ) ι ₂ (Si0) ι x 27 H ₂ 0), insoluble sodium metaphosphate (Na P0 ₃ ) _n and hydroxylapatite.

Examples of humectants are polyols such as glycerol, propylene glycol, sorbitol and xylitol.

According to a particularly preferred embodiment, the ratio of microparticles to the oral care product according to the invention is

Humectants - insofar as humectants are added - 4: 1 to 1: 4, preferably 3: 1 to 1: 3 and in particular 2: 1 to 1: 2.

In addition to the microparticles according to the invention, examples of binders are cellulose derivatives, carageen and silicas.

Examples of preservatives are 4-hydroxybenzoic acid ester or sodium benzoate.

Examples of sweeteners are saccharin, sodium and calcium cyclamate, sorbitol and other sweeteners that are not cariogenic.

Examples of flavoring agents are peppermint oil, spearmint oil, wintergreen oil, myrrh and fruit flavors, in particular for children's toothpastes. Special active ingredients can, for example, fluorine compounds for the

Tooth decay prevention, such as sodium fluorophosphate, alkali fluoride, zinc fluoride and

Quartz ammonium fluoride. Active ingredients can also be used to care for the inflamed

Gums can be added, such as azulene, allantonin and bisabolol, as well as plant extracts (chamomile, myrrh etc.)

Strontium salts, potassium nitrates and citrates can be added to reduce sensitivity.

As far as the toothpaste or the tooth powder is supposed to work against colored deposits and stains on the teeth, they can contain a particularly high abrasive content.

The toothpaste is whitened by the microparticles according to the invention itself or when required, for example if the microparticles are only added in small amounts, for example to act as a carrier for active ingredients

Addition of titanium dioxide causes.

According to a further embodiment, the oral care product according to the invention can be a mouthwash. In general, mouthwashes serve less for cleaning the teeth and the oral cavity, but rather for refreshment and

Masking bad breath. In the mouthwashes according to the invention, the microparticles therefore preferably serve as a carrier material for additives such as flavorings, sweeteners and special nourishing active ingredients.

Mouthwashes contain essentially 20: 1 to about 2: 1 of a water-ethyl

Alcohol solution and other additives such as flavors, sweeteners, humectants and surfactants, such as have been described above, for example. Examples of surfactants are sodium lauryl sulfate, sodium lauroyl sarcosinate, medicinal salts, palm kernel fatty acid tauride, sodium lauryl sulfoacetate, coconut fatty acid monoglyceride sulfonate and betaines.

The frame structure of a mouthwash usually contains from about 5% by weight to about 60% by weight of ethyl alcohol, to about 20% by weight of a humectant, to about 2.0% by weight of a dispersing aid, up to about 0.5% by weight of sweetener, up to about 0.3% by weight of flavoring agent and the rest water.

Because of the good dispersibility of the microparticles used according to the invention, the mouthwashes according to the invention are particularly well suited for use as a mouth spray in compressed gas packs. According to a further embodiment, the oral care products according to the invention can be lozenges and chewing gums for oral hygiene.

Pastilles are particularly used to impart a fresh bad breath. In this case, the microparticles can be used as tablet binders and also act as a carrier material for additives, such as flavors, etc.

Chewing gums for oral care are particularly useful for quick cleaning, as long as cleaning with a toothbrush is not possible, for example on the go, and at the same time to conceal bad breath. In this case, the microparticles can act in particular as a cleaning agent and as a carrier material for additives, such as flavorings and other additives, as are customary in such chewing gums. Chewing gums usually contain homo- and copolymers, such as polyethylene ether, polyvinyl isobutyl ether, polyisobutylene, polyvinyl acetates and others.

Another area of application for the oral care products according to the invention is denture and prosthesis care. Means for this are summarized below as "denture cleaners". Denture cleaners are usually effervescent tablets and powders for dissolving in water. They usually contain surfactants, complexing agents,

Per compounds, agents for adjusting the pH value, carbon dioxide releasers and other additives, such as enzymes, which promote cleaning by splitting proteins.

When used in denture cleaners, the microparticles can be used in particular as

Act carriers of active substances that gradually release them. This is of particular importance for long-term cleaning products in which the denture or the prosthesis must remain for several hours, for example overnight. It is understood that for the oral care products according to the invention also others

Components and formulations can be used as they are numerous in the

Literature are described. For example, the

Monograph "Cosmetics, Development, Production and Application of Cosmetics", edited by Wilfried Umbach, pages 181 to 223, (1988) Georg

Thieme Verlag Stuttgart, New York, and “Cosmetic products for tooth and

Oral Care "in Hager's Handbook of Pharmaceutical Practice, 5th edition, pages

191 to 197.

In these references, further examples of the above-mentioned components of oral care products and recipe examples are given, as can in principle also be used for the present invention.

The present invention is described below with reference to individual exemplary embodiments, these examples being intended to illustrate the invention and not to limit the present invention.

example 1

In vitro production of a linear water-insoluble poly-1, 4-α-D-glucan in a biocatalytic process with amylosucrase.

15 I of a 20% sucrose solution are placed in a sterilized (steam sterilization) 25 I vessel. 120 ml of the enzyme extract containing amylosucrase is added in one portion. The enzyme activity in this experiment is 20 units (1 unit = 1 μmol sucrose x min ^"1 x mg enzyme). The apparatus is equipped with a KPG stirrer that is also sterilized. The vessel is closed, stored at 39 ° C. and stirred. Already A white precipitate forms after a few hours. The reaction is ended after 54 hours. The precipitate is filtered off and washed twice with water to separate off low-molecular sugar. The residue remaining in the filter is placed in a drying cabinet at 38 ° C. Creation of a

Vacuum dried using a membrane pump (Vacuubrand GmbH & Co., CVC 2). The mass is 893 g (yield 59%). (Molecular weights: Mw = 9,000 g / mol; M _n = 4,400 g / mol; M _w / M _w = 2.05; GPC, solvent DMSO, calibration with pullulan standards).

Example 2 Production of Microparticles from Poly-1, 4-α-D-glucan

200 g of poly-1,4-α-D-glucan are rapidly dissolved in about 1 liter of dimethyl sulfoxide (DMSO, p.a. from Ridel-de-Haen) at 50 ° C. The solution is slowly added in 8 l of double-distilled water with stirring through a dropping funnel. The mixture is stored at 4 ° C. overnight. The fine suspension of the

Particles are separated by decantation. The sediment is slurried and centrifuged (RC5C ultracentrifuge: 5 minutes at 5,000 revolutions per minute). The solid residue is slurried three times with bidistilled water and centrifuged. The solids are collected and the still moist suspension of approx. 1000 ml freeze-dried (Christ Delta 1-24 KD). 176 g of white solid are isolated (yield 88%). The surface of the particles is spherical in shape. The majority of the particle diameters are in the range of 2-3 μm. The specific surface is 3.75 m ² / g (method: Sorptomatic 1990 (from Fisons Instruments)).

Example 3

500 mg of poly-1,4-α-D-glucan are dissolved in 2.5 ml of dimethyl sulfoxide (DMSO, p.a. from Riedel-de-Haen) at approx. 70 ° C. The DMSO solution is added dropwise in 100 ml of double-distilled water with stirring and the solution is kept at 5 ° C. overnight. The fine milky suspension is centrifuged for 15 minutes at 3500 revolutions per minute and the supernatant is decanted off. The sediment is slurried with double-distilled water and centrifuged again. The process is repeated two more times. The suspension is then freeze-dried. 311 mg of white poly-1,4-α-D-glucan particles are obtained.

This corresponds to a yield of 62% colorless microparticles.

Example 4

Production of toothpastes using the microparticles according to Example 2

Two toothpastes with the composition according to the following table were evaluated.

Both toothpastes showed excellent cleaning results, did not change their consistency even after a long period of opening and were subjectively evaluated by test persons with regard to their sensory properties, e.g.

Feeling when brushing your teeth, rated very positively.

Component content (% by weight)

Example a Example b

Carboxymethyl cellulose 1.5 1, 5

Glycerin 40.0 30.0

Titanium dioxide 2.0 2.0

Calcium carbonate 5.0 7.5

Sodium dodecyl sulfate 1.0, 1.0

(SDS)

Microparticles 20.0 17.5

Rest of water

Claims

claims

1. Oral care products which contain spherical microparticles as an essential component, which consist wholly or partly of at least one water-insoluble linear polyglucan.

2. Oral care product according to claim 1, characterized in that the spherical microparticles have an average diameter of 1 nm to 100 microns.

3. Oral care product according to claim 1 or 2, characterized in that the depth of irregularities on the particle surface is at most 20% of the average diameter of the spherical microparticles.

4. Oral care product according to one of the preceding claims, characterized in that the microparticles are contained in the oral care product in an amount of up to 90% by weight, based on the total weight of the oral care product.

5. mouth care product according to one of the preceding claims, characterized in that the at least one water-insoluble polyglucan poly-1, 4-α-D-glucan and / or poly-1, 3-ß-D-glucan, in particular poly-1, 4-α-D-glucan.

6. Oral care product according to one of the preceding claims, characterized in that the at least one water-insoluble linear polyglucan has been obtained by a biotechnological method.

7. Oral care product according to one of the preceding claims, characterized in that the at least one water-insoluble polyglucan has been produced biocatalytically.

8. Oral care product according to one of the preceding claims, characterized in that the proportion of water-insoluble linear polyglucan in the microparticles is at least 70%, based on the total polyglucan content, including optionally branched polysaccharide and other polymers.

9. Oral care product according to one of the preceding claims, characterized in that the microparticles consist 100% of at least one water-insoluble linear polyglucan.

10. Oral care product according to one of the preceding claims, characterized in that the oral care product is selected from mouthwashes,

Mouth powder, mouth pills, mouth sprays, dentures, prostheses and dentifrices and plaque stain tablets.

11. Oral care product according to claim 10, characterized in that the dental care product is selected from toothpastes, tooth gels,

Tooth cleaning powder chewing gum.

12. Use of microparticles, which consist wholly or partly of at least one water-insoluble linear polyglucan, in dentifrices.