DE102006009782A1 - Remineralizing products - Google Patents

Abstract

The present application relates to remineralizing products according to the teaching of DE 102005060182.0, which contain at least one calcium salt in the form of particles that are rod-shaped and / or platelet-shaped, preferably predominantly platelet-shaped.

Description

The present application is an additional application to the earlier German patent application DE 10 2005 060 182.0 from 14.12.2005.

The The main application concerns products which, because of special Ingredients remineralizing and / or neomineralizing act and in a variety of forms can. In some of the possible In addition, the products have a high cleaning performance, without the tooth surface too scratch or too abrasive to act and prevent beyond the discomfort of bad breath and reduce bad breath.

• a) ≥ 0,005 bis < 10 Gew.-% mindestens eines Calciumsalzes;
• b) ≥ 0,005 bis < 10 Gew.-% mindestens einer salivationsfördernden Substanz.

In a first embodiment, the main application relates to remineralizing products for oral use, containing - based on their weight -

• a) ≥ 0.005 to <10% by weight of at least one calcium salt;
• b) ≥ 0.005 to <10 wt .-% of at least one salivationsfördernden substance.

This additional application concerns remineralising products according to the teaching of DE 10 2005 060 182.0 containing calcium salts of particular morphology.

The subject of this application is remineralising products for oral use according to the teaching of DE 10 2005 060 182.0 , characterized in that they contain at least one calcium salt in the form of particles which are rod-shaped and / or platelet-shaped, preferably predominantly platelet-shaped.

Surprisingly has succeeded in including calcium salts or composite materials these provide a predominantly platelike structure of the hard water-soluble Have calcium salt and thus the bone substance especially good at imitating. Predominantly platelet-shaped in the context of the present invention that at least 50%, preferably at least 70%, more preferably at least 80% of the particles in the form of platelets available. Particularly preferably, the particles have a substantially platelet-like Shape up.

advantageously, are the invention to be used Calcium salts or composite materials comprising these, with the predominantly flaky Calcium particles of the structure of the bone substance in vivo, which also Made of plates, especially similar. This has the special Advantage that they are due to the similarity of the form with the biological apatites (for example bone or dentin apatite) a particularly good ability have to re - and neomineralization, so that the process of Biomineralization can take place even faster and better.

One Another advantage of the invention is that the poorly water-soluble Calcium salts or composite materials, including these, with a predominantly platelike Structure of the calcium salts have improved biocompatibility.

The Determination of the particle diameter of the crystallites can by the Professional common methods be determined, in particular by the evaluation of the X-ray diffraction observed broadening of the reflexes. Preferably takes place the evaluation by Fit method for example, the Rietveld method.

According to one particular embodiment the products of the invention poorly water-soluble Calcium salts and / or the composite materials comprising these, in the form of platelet-shaped particles with a width in the range of 5 to 150 nm and a length in the range from 10 to 150 nm as well as a height (Thickness) from 2 to 50 nm.

According to one particularly preferred embodiment is the average length the particle preferably 30 to 100 nm. Preferably, the width is this particle in the range between 10 to 100 nm.

The Determination of the particle diameter of the particles can be carried out by a person skilled in the art common Methods are determined, in particular by the evaluation of Imaging methods, in particular transmission electron microscopy.

Under Height (thickness) Here is the smallest diameter of the particles in relation to the three to understand mutually perpendicular spatial directions, under Length her largest diameter. The width of the particles is therefore the other perpendicular to the length Diameter equal to or smaller than the length dimension of the particle, but bigger or at least equal to its height dimension is.

The platelet-shaped particles lie as more or less irregularly shaped particles, partially as rather round, partly rather angular particles also with rounded ones Edges in front. This is especially noticeable in the pictures, which are recorded by means of transmission electron microscopy can.

The platelet-shaped particles often also overlap several times in such samples. Overlapping particles are typically imaged at the points of overlap with greater blackening than non-overlapping particles. The specified lengths, free and heights are preferably determined (measured) on non-overlapping particles of the sample.

The height of platelet-shaped particles can from such recordings preferred by the determination of the dimensions the one with its largest surface vertical to the image plane standing particles are obtained. The vertical particles standing to the image plane are characterized by a particularly high contrast (high density) and appear more like a rod. These platelet-shaped particles which are perpendicular to the image plane can be referred to as indeed be identified standing perpendicular to the image plane, when at a tilting of the image plane a broadening of the dimension (at least in a spatial direction) and show a decrease in the density of the image.

to Determination of height it is particularly suitable for the particle to multiply the image plane of the sample in different positions to tilt and the dimensions of the particles in the setting to determine by the highest contrast / highest darkness and the smallest extent of the particles is characterized. The shortest extent then corresponds to the height the particle.

According to one particular embodiment is in the Particles of the invention difficult water-soluble Calcium salts and / or composite materials, including these, the relationship of length to width between 1 and 4, preferably from 1 to 3, particularly preferred between 1 and 2, for example, 1.2 (length 60 nm, width 50 nm) or 1.5 (length 80, width 40 nm).

The flaky Shape of the particles is formed by the ratio of length to width. Is the ratio between Length and Width significantly larger than 4, are more rod-shaped particles in front.

Of the Advantage of the platelet-shaped particles with a relationship of preferably 1 to 2 is that these particles are natural Bone material very similar Length too Have a width ratio and therefore a particularly good and biologically compatible or neomineralization of the dental material (dentin and enamel).

According to a further particular embodiment, the particles have an area of 0.1 × 10 ^-15 m ² to 90 × 10 ^-15 m ² , preferably an area of 0.5 × 10 ^-15 m ² to 50 × 10 ^-15 m ² , particularly preferably 1.0 × 10 ^-15 m ² to 30 × 10 ^-15 m ² , very particularly preferably 1.5 × 10 ^-15 m ² to 15 × 10 ^-15 m ^2, for example 2 × 10 ^-15 m ² ,

When area the particle becomes the surface the plane, spanned by the length and the vertical Width, according to the usual determined by geometric calculation methods.

Surprisingly succeeded with the present invention, the calcium salts of the invention or composite materials, including these, in the form of crystalline to produce inorganic nanoparticles, which is a particular effective neomineralization of dental material (dentin and enamel) and bone tissue.

According to one another preferred embodiment contains the remineralising product - by weight - 0,01 to 5 wt .-%, preferably 0.02 to 2.5 wt .-%, more preferably 0.03 to 1 wt .-%, more preferably 0.04 to 0.75 wt .-% and in particular 0.05 to 0.5 wt .-% calcium salt (s) in the form of individual crystallites or in the form of platelet-shaped particles, comprising a plurality of said crystallites, wherein a single Crystallite has a thickness in the range of 2 to 50 nm and a length in the range from 10 to 150 nm, preferably a thickness of 2 to 15 nm and a length of 10 to 50 nm; more preferably a thickness of 3 to 7 nm and a length of 15 to 25 nm.

alternative to the above embodiment or in addition can do this the products of the invention the nanoparticulate calcium salts also in the form of composite materials.

• a. in Wasser schwerlösliche Calciumsalze, wobei die Calciumsalze in Form von einzelnen Kristalliten oder in Form von Partikeln, umfassend eine Mehrzahl besagter Kristallite, mit einem mittleren Teilchendurchmesser im Bereich von unter 1000 nm, bevorzugt unter 300 nm vorliegen, und
• b. eine Polymerkomponente,

wobei die Partikel im Kompositmaterial stäbchen- und/oder plättchenförmig, bevorzugt vorwiegend plättchenförmig sind.According to a particular embodiment, the remineralizing product contains a composite material comprising

• a. sparingly soluble calcium salts in water, wherein the calcium salts in the form of individual crystallites or in the form of particles comprising a plurality of said crystallites, having an average particle diameter in the range of less than 1000 nm, preferably less than 300 nm, and
• b. a polymer component,

wherein the particles in the composite material are rod-shaped and / or platelet-shaped, preferably predominantly platelet-shaped.

According to one particularly preferred embodiment is the polymer component of, in the remineralizing product contained composite material selected from a protein component, Polyelectrolytes and polysaccharides.

A preferred embodiment of the invention is that as the polymer component Polyelectrolytes are used.

When Polyelectrolytes come within the meaning of the invention polyacids and Polybases into consideration, wherein the polyelectrolytes biopolymers or may also be synthetic polymers. So included the

• – Alginsäuren
• – Pektinen
• – Carrageenan
• – Polygalakturonsäuren
• – Amino- und Aminosäurederivaten von Alginsäuren, Pektinen, Carrageenan und Polygalakturonsäuren
• – Polyaminosäuren, wie z. B. Polyasparaginsäuren
• – Polyaspartamiden
• – Nucleinsäuren, wie z. B. DNA und RNA
• – Ligninsulfonaten
• – Carboxymethylcellulosen
• – Amino- und/oder Carboxylgruppen-haltigen Cyclodextrin-, Cellulose- oder Dextran-Derivaten
• – Polyacrylsäuren
• – Polymethacrylsäuren
• – Polymaleinaten
• – Polyvinylsulfonsäuren
• – Polyvinylphosphonsäuren
• – Polyethyleniminen
• – Polyvinylaminen

sowie Derivaten der vorstehend genannten Stoffe, insbesondere Amino- und/oder Carboxyl-Derivaten. Bevorzugt werden im Rahmen der vorliegenden Erfindung Polyelektrolyte eingesetzt, die zur Salzbildung mit zweiwertigen Kationen geeignete Gruppen tragen. Insbesondere eignen sich Carboxylat-Gruppen tragende Polymere.compositions according to the invention, for example one or more polyelectrolytes selected from

• - Alginic acids
• - pectins
• - carrageenan
• - Polygalacturonic acids
• Amino and amino acid derivatives of alginic acids, pectins, carrageenan and polygalacturonic acids
• - Polyamino acids, such as. B. polyaspartic acids
• - polyaspartamides
• - Nucleic acids, such as. B. DNA and RNA
• - lignosulfonates
• - carboxymethylcelluloses
• - Amino- and / or carboxyl-containing cyclodextrin, cellulose or dextran derivatives
• - polyacrylic acids
• - polymethacrylic acids
• - polymaleinates
• - Polyvinylsulfonic acids
• - Polyvinylphosphonic
• - Polyethyleneimines
• - Polyvinylamines

and derivatives of the abovementioned substances, in particular amino and / or carboxyl derivatives. In the context of the present invention, preference is given to using polyelectrolytes which carry suitable groups for salt formation with divalent cations. In particular, polymers bearing carboxylate groups are suitable.

in the Particularly preferred polyelectrolytes according to the invention are polyaspartic acids, alginic acids, pectins, deoxyribonucleic acids, ribonucleic acids, polyacrylic and polymethacrylic acids.

All particularly preferred are polyaspartic acids having a molecular weight in the range between about 500 and 10,000 daltons, in particular 1000 up to 5000 daltons.

A Another preferred embodiment of the Invention is that as the polymer component polysaccharides selected are. In particular, these polysaccharides are selected from glucuronic acid and / or Iduronsäurehaltigen Polysaccharides. These are to be understood as meaning polysaccharides among others, glucuronic acid, preferred D-glucuronic acid, and / or Iduronic acid, in particular L-iduronic, are constructed. An ingredient of the carbohydrate scaffold becomes of glucuronic acid or iduronic acid educated. Glucuronic acid isomeric iduronic acid has the other configuration at the C5 carbon atom of the ring. Preference is given to glucuronic acid and / or iduronic Polysaccharides to understand such polysaccharides, the glucuronic acid and / or iduronic in a molar ratio from 1:10 to 10: 1, especially from 1: 5 to 5: 1, more preferably 1: 3 to 2: 1, based on the sum of the other Monosaccharidbausteine of the polysaccharide. Advantageously, by the anionic carboxyl groups of glucuronic acid and / or iduronic acid Polysaccharides a particularly good interaction with the calcium salt be achieved, which leads to a particularly stable and at the same time lead particularly well biomineralizing composite material. For example suitable polysaccharides are the glucuronic acid and / or iduronic acid-containing Glycosaminoglycans (also called mucopolysaccharides), microbial produced xanthan gum or welan or gum arabic which is made from Acacia is obtained.

One Advantage of the invention used Composite materials is the particular stability in aqueous systems even without Addition of dispersing aids such as polyhydric alcohols (such as Glycerol or polyethylene glycols).

• a) 0,1 bis 80 Gew.-%, vorzugsweise 10 bis 60 Gew.-% und insbesondere 30 bis 50 Gew.-% Proteinkomponenten ausgewählt aus Proteinen, Proteinhydrolysaten und Proteinhydrolysat-Derivaten;
• b) 0,01 bis 80 Gew.-%, vorzugsweise 10 bis 75 Gew.-% und insbesondere 30 bis 65 Gew.-% des bzw. der Calciumsalzes) in Form von einzelnen Kristalliten oder in Form von stäbchenförmigen Partikeln, umfassend eine Mehrzahl besagter Kristallite, wobei ein einzelner Kristallit eine Dicke im Bereich von 2 bis 50 nm und eine Länge im Bereich von 10 bis 150 nm aufweist,

enthalten.Furthermore, products according to the invention are preferred which contain the calcium salt (s) in the form of individual crystallites or in the form of platelet-shaped particles comprising a plurality of said crystallites, wherein a single crystallite has a thickness in the range from 2 to 50 nm and a length in Range of 10 to 150 nm, in the form of composite materials containing, based on the weight of the composite material,

• a) 0.1 to 80 wt .-%, preferably 10 to 60 wt .-% and in particular 30 to 50 wt .-% protein components selected from proteins, protein hydrolysates and protein hydrolyzate derivatives;
• b) 0.01 to 80 wt .-%, preferably 10 to 75 wt .-% and in particular 30 to 65 wt .-% of the or the calcium salt) in the form of individual crystallites or in the form of rod-shaped particles, comprising a plurality said crystallites, wherein a single crystallite has a thickness in the range of 2 to 50 nm and a length in the range of 10 to 150 nm,

contain.

According to a very particularly preferred embodiment, the protein component of, in The composite material containing the remineralizing product selected from collagen, gelatin, casein and their hydrolysates, preferably gelatin, more preferably gelatin of type A, B or AB, in particular gelatin of the type acid bone (AB).

Especially suitable for the preparation of a calcium salt or composite material according to the invention, which predominantly platelet-shaped particles contains will the precipitation the calcium salt or the composite material at a pH between 5 and 9, preferably between 6 and 8, more preferably performed around 7.

Preferential for the formation of the inventively preferred Composite material thereby a solution a calcium salt with the polymer component and presented a Phosphate solution slowly added, the pH between 5 and 9, preferably between 6 and 8, more preferably around 7 lies. Particularly preferred way is the pH at the addition of the phosphate solution by adding appropriate Amounts of aqueous base kept constant.

object The main application is also the use of mixtures of calcium salts and salivationsfördernden Substances in agents that are introduced into the oral cavity as well the use of mixtures of calcium salts and salivation-promoting Substances for remineralization and / or Neominersalisierung of Teeth.

object This additional application is also the use of mixtures Calcium salts, in the form of particles, the rod and / or platelet-shaped, preferably are predominantly platelet-shaped, and salivating Substances in agents that are introduced into the oral cavity as well the use of mixtures of calcium salts, in the form of particles, the chopsticks and / or platelet-shaped, preferably are predominantly platelet-shaped, and salivating Substances for remineralization and / or Neominersalisierung of Teeth.

Claims (9)

Remineralizing products for oral use according to the teaching of DE 10 2005 060 182.0 , characterized in that it contains at least one calcium salt in the form of particles which are rod-shaped and / or platelet-shaped, preferably predominantly platelet-shaped. Remineralizing products according to claim 1, characterized characterized in that the platelet-shaped particles a length from 10 to 150 nm and a width of 5 to 150 nm, preferably a length of 30 to 100 nm and a width of 10 to 100 nm. Remineralizing products according to one of claims 1 or 2, characterized in that the particles have a ratio of Length too Width of 1 to 4, preferably from 1 to 3, more preferably between 1 to 2 have. Remineralizing product according to one of the preceding claims, characterized in that the particles have an area of 0.1 × 10 ^-15 m ² to 90 × 10 ^-15 m ² , preferably an area of 0.5 × 10 ^-15 m ² to 50 10 ^-15 m ² , particularly preferably 1.0 × 10 ^-15 m ² to 30 × 10 ^-15 m ² , very particularly preferably 1.5 × 10 ^-15 m ² to 15 × 10 ^-15 m ² . Remineralizing product according to one of the preceding Claims, characterized in that it - based on its weight - 0.01 to 5 wt .-%, preferably 0.02 to 2.5 wt .-%, more preferably 0.03 to 1 wt .-%, more preferably 0.04 to 0.75 wt .-% and in particular 0.05 to 0.5% by weight of calcium salts) in the form of individual crystallites or in the form of platelet-shaped particles a plurality of said crystallites, wherein a single crystallite a thickness in the range of 2 to 50 nm and a length in the range of 10 to 150 nm, preferably a thickness of 2 to 15 nm and a length of 10 to 50 nm; more preferably a thickness of 3 to 7 nm and a length of 15 to 25 nm. Remineralizing product according to one of the preceding Claims, characterized in that it contains a composite material comprising c. sparingly soluble in water Calcium salts, wherein the calcium salts in the form of individual crystallites or in the form of particles comprising a plurality of said crystallites, with an average particle diameter in the range of less than 1000 nm, preferably below 300 nm, and d. a polymer component, in which the particles in the composite rod-shaped and / or platelet-shaped, preferably predominantly platelet-shaped. Remineralizing product according to claim 6, characterized in that the polymer component of the composite material contained is selected from a protein component, polyelectrolytes and polysaccharides. Remineralizing product according to claim 7, characterized in that said protein component is selected from collagen, gelatin, casein and their hydrolysates, preferably gelatin, more preferably gelatin type A, B or AB, in particular gelatin type acid bone. Use according to the teaching of DE 10 2005 061 182.0 , characterized in that the calcium salts, in the form of particles, the rod and / or platelet-shaped, preferably present predominantly platelet-shaped.