阅读说明：本技术 口腔护理组合物 (Oral care compositions ) 是由 李艳晓 岳红雷 于 2019-10-24 设计创作，主要内容包括：本发明公开了一种口腔护理组合物,包括：片状羟基磷灰石颗粒和口腔可接受的载体；所述片状羟基磷灰石厚度与平均粒径的比值小于0.4。本发明口腔护理组合物能显著减少封堵牙小管后的再次暴露,在牙齿上的再矿化性能有明显的提高,且该组合物中的游离氟离子的稳定性有了显著地提高。(The present invention discloses an oral care composition comprising: flaky hydroxyapatite particles and an orally acceptable carrier; the ratio of the thickness of the flaky hydroxyapatite to the average particle size is less than 0.4. The oral care composition of the invention can significantly reduce the re-exposure after the occlusion of the dental tubules, significantly improve the remineralization performance on the teeth, and significantly improve the stability of the free fluoride ions in the composition.)

1. An oral care composition characterized by comprising:

plate-like hydroxyapatite particles, and

an orally acceptable carrier;

the thickness of the flaky hydroxyapatite particles is less than 100 nanometers, and is preferably 38-42 nanometers; the ratio of the thickness to the average particle size is less than 0.4.

2. The oral care composition of claim 1, wherein: the flaky hydroxyapatite particles account for 0.01-50% of the oral care composition by mass; preferably 0.1 to 10%; more preferably 0.5 to 5%.

3. The oral care composition of claim 1, wherein: the oral care composition further comprises a polycarboxyl compound.

4. The oral care composition of claim 1, wherein: the polycarboxyl compound accounts for 0.01 to 10 percent of the mass of the oral care composition, preferably 0.1 to 5 percent of the mass of the oral care composition, and more preferably 0.5 to 3 percent of the mass of the oral care composition.

5. The oral care composition of claim 1, wherein: the polycarboxyl compound is one or more of a citrate compound, a polyaspartate, an iminodisuccinate, a 2-phosphonobutane-1, 2, 4-tricarboxylate and a polyacrylate.

6. The oral care composition of claim 5, wherein: the polycarboxyl compound is a citrate compound.

7. The oral care composition of claim 1, wherein: the oral care composition further comprises a fluoride ion source.

8. The oral care composition of claim 1, wherein: the fluoride ion source provides 100-2000ppm of fluorine element; more preferably, 500-1500ppm of elemental fluorine is provided; most preferably, 900-.

9. The oral care composition of claim 7, wherein: the fluoride ion source is one or more of sodium fluoride, potassium fluoride, calcium fluoride, magnesium fluoride, stannous fluoride, ammonium fluoride, sodium monofluorophosphate, potassium monofluorophosphate, fluorosilicate and olaflur.

10. The oral care composition of claim 1, wherein: the oral care composition comprises a toothpaste, gel, mouthwash or tooth powder.

Technical Field

The invention relates to the technical field of oral care, in particular to an oral care composition.

Background

Tooth sensitivity is a common disease in stomatology, and sensitive teeth can cause ache symptoms due to external stimulation such as temperature (cold and heat), chemical substances (acid and sweet), mechanical action (friction or hard biting), and the like. It is widely believed that the reason for tooth hypersensitivity is excessive exposure of dentinal tubules, excessive internal and external flow of dentinal tubule liquid in the dentinal tubules caused by external stimulation, and mechanical stimulation of pulp nerve endings sensitive to pressure to generate impulse and conduct pain sensation. In the prior art, potassium ions are generally adopted to reduce the sensitivity of nerve endings or a tubule plugging material is adopted to plug exposed tubules so as to achieve the aim of improving the allergic symptoms.

Hydroxyapatite (HAp) is the main inorganic component of teeth, has good bioactivity and biocompatibility, and can be used for occlusion of dental tubules. For example: chinese patent application CN1751678A discloses a toothpaste with tooth filling and anti-caries functions and a formula thereof, wherein active nano-scale biological ceramic material hydroxyapatite is added into the toothpaste. The hydroxyapatite is easy to be absorbed on the surface of the defect of the tooth in the process of brushing the teeth and is tightly combined with the tooth, thereby achieving the effects of repairing and reinforcing the tooth. Even so, the repaired tooth still has the risk of tooth tubules being exposed again in the subsequent brushing process, and the person in the art is called "re-demineralization" for short, and the remineralization performance of the tooth must be improved in order to reduce the tooth tubules being exposed again in the subsequent brushing process. For example, chinese patent application CN1751678A discloses that needle-shaped hydroxyapatite with a particle size of 50 nm or less has better remineralization hardness, demineralization coverage and adsorption to demineralized teeth.

For another example: chinese patent application CN105686960A discloses a tooth anti-sensitivity composition comprising hydroxyapatite, a polycarboxyl compound, soluble calcium and an orally acceptable carrier. The composition can enter the dentinal tubules to occlude the dentinal tubules. The hydroxyapatite disclosed in this document is a needle-like or rod-like hydroxyapatite.

In view of the above, no further research has been done on the remineralizing potential of oral care compositions in the prior art.

Disclosure of Invention

The technical problem to be solved by the invention is to provide an oral care composition. The oral care composition can significantly reduce re-exposure after occlusion of the dental tubules and significantly improve remineralization properties on teeth.

In order to solve the technical problems, the invention adopts the following technical scheme:

an oral care composition comprising:

plate-like hydroxyapatite particles, and

an orally acceptable carrier;

the thickness of the flaky hydroxyapatite particles is less than 100 nanometers, and the ratio of the thickness to the average particle size is less than 0.4. The average particle size is the average value of the particle sizes of the flaky hydroxyapatite particles.

Preferably, the thickness of the plate-shaped hydroxyapatite particles is 38-42 nanometers.

Preferably, the plate-shaped hydroxyapatite accounts for 0.01-50% of the oral care composition by mass.

As a further improvement of the technical solution, the oral care composition further comprises a polycarboxyl compound.

Preferably, the polycarboxyl compound is present in an amount of 0.01% to 10% by weight of the oral care composition.

Preferably, the polycarboxyl compound is one or more of a citrate compound, a polyaspartate, an iminodisuccinate, a 2-phosphonobutane-1, 2, 4-tricarboxylate and a polyacrylate.

Preferably, the polycarboxyl compound is a citrate compound.

As a further improvement of the technical solution, the oral care composition further comprises a fluoride ion source.

Preferably, the fluoride ion source provides 100-; more preferably, 900-;

preferably, the fluoride ion source is one or more of sodium fluoride, potassium fluoride, calcium fluoride, magnesium fluoride, stannous fluoride, ammonium fluoride, sodium monofluorophosphate, potassium monofluorophosphate, fluorosilicate, olaflur.

Preferably, the oral care composition comprises a toothpaste, gel, mouthwash or tooth powder.

Any range recited herein is intended to include the endpoints and any number between the endpoints and any subrange subsumed therein or defined therein.

The starting materials of the present invention are commercially available, unless otherwise specified, and the equipment used in the present invention may be any equipment conventionally used in the art or may be any equipment known in the art.

Compared with the prior art, the invention has the following beneficial effects:

the oral care composition of the invention can significantly reduce the re-exposure after occlusion of the dental tubules, significantly improve the remineralization performance on teeth, and significantly improve the stability of free fluorine in the composition.

Drawings

FIG. 1 is a Scanning Electron Microscope (SEM) image of the surface of a dentin sample after acid etching;

FIG. 2 is a scanning electron microscope photograph of a dentin sample after 7 days of brushing with a toothpaste using hydroxyapatite rod in comparative example 1;

FIG. 3 is a scanning electron microscope photograph of a dentin sample after 7 days of brushing with a toothpaste using plate-like hydroxyapatite of example 1;

FIG. 4 is an enlarged scanning electron microscope photograph of the cross-sectional dentin of FIG. 2;

FIG. 5 is an enlarged scanning electron microscope photograph of the cross-sectional dentin of FIG. 3;

FIG. 6 is a scanning electron microscope image of a dentin sample 7 days after empty brushing of the experimental bovine teeth of FIG. 2;

FIG. 7 is a scanning electron microscope image of a dentin sample 7 days after the empty brush of the experimental bovine teeth of FIG. 3;

FIG. 8 is a scanning electron microscope photograph of a dentin sample 3 days after brushing with the formulation of example 1;

FIG. 9 is a scanning electron microscope photomicrograph of a dentin sample 3 days after brushing with the comparative example 2 formulation;

FIG. 10 is a scanning electron microscope photograph of a dentin sample 3 days after brushing with the formulation of example 2;

FIG. 11 is a scanning electron microscope image of a conventional sheet-like hydroxyapatite;

FIG. 12 is a scanning electron microscope photograph of a needle-shaped hydroxyapatite of the prior art;

fig. 13 is a scanning electron microscope image of a conventional rod-shaped hydroxyapatite.

Detailed Description

In order to more clearly illustrate the invention, the invention is further described below in connection with preferred embodiments. It is to be understood by persons skilled in the art that the following detailed description is illustrative and not restrictive, and is not to be taken as limiting the scope of the invention.

All percentages and ratios used herein are by weight of the total composition, unless otherwise specified. Unless otherwise indicated, all percentages, ratios, and levels of ingredients referred to herein are based on the actual amount of the ingredient, and do not include solvents, fillers, or other materials found in commercially available products with which the ingredient may be combined.

The term "comprising" as used herein means that other steps and ingredients which do not affect the end result can be added.

The term "preferably" and its variants herein refer to embodiments of the invention that are capable of providing specific benefits under specific circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, the detailed description of one or more preferred embodiments does not indicate that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the invention.

The method is carried out according to conventional conditions or conditions recommended by manufacturers if specific conditions are not indicated in the examples of the invention; the reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.

As one aspect of the present invention, an oral care composition comprises:

plate-like hydroxyapatite particles, and

an orally acceptable carrier;

the thickness of the flaky hydroxyapatite particles is less than 100 nanometers, and the ratio of the thickness to the average particle size is less than 0.4. The average particle size is the average value of the particle sizes of the flaky hydroxyapatite particles.

In certain embodiments of the invention, the plate-like hydroxyapatite particles have a thickness of 38 to 42 nanometers.

It has been surprisingly found that by adding plate-like hydroxyapatite particles to an oral care composition and having a thickness to particle size in a particular ratio range, the resulting oral care composition has better remineralisation properties than other types of hydroxyapatite (rod or needle-like). That is, the oral care composition of the present invention significantly reduces re-exposure after occlusion of the tubules and significantly improves the stability of free fluorine in the formulation.

Dentin is an important component of teeth. Dentin tubules are distributed in the dentin in an arrangement mode and radiate from a enamel dentin interface at the dental pulp end. It is generally believed that when dentinal tubules are exposed at the opening of the dentinal surface, and exposed to cold, heat, acid, sweet, mechanical or chemical stimuli, the pulp nerve endings become excited, producing transient pain, i.e., dentinal hypersensitivity. Studies have shown that dentin sensitive individuals have a greater number of open dentinal tubules and a greater average diameter than dentin insensitive individuals. Thus, dentinal sensitivity may be alleviated or treated by occluding the dentinal tubules to reduce the permeability of the dentin.

An important component of dentin is hydroxyapatite, HAp for short. The hydroxyapatite has good biocompatibility and can be used for plugging dentinal tubules. The prior haps on the market have three morphologies, namely needle HAp, rod HAp and flake HAp. Wherein:

rod-shaped: rod-like hydroxyapatite generally refers to a solid nano material with a straight one-dimensional cylindrical longitudinal shape (or a polygonal cross section). Typically, the particles are 80-100nm in length and about 20nm in width (see FIG. 13).

Needle-shaped: the needle-shaped nano hydroxyapatite particles have a straight longitudinal shape, and the diameters of two ends or one end of the needle-shaped nano hydroxyapatite particles are thinner and sharper than those of the middle diameter of the particles (see figure 12).

Sheet-shaped: the flaky nano hydroxyapatite is a two-dimensional structure material, the thickness is generally below 100 nanometers, the diameter can reach tens of nanometers, hundreds of nanometers or even reach the micrometer level, and the ratio of the thickness to the diameter is less than 0.4 (see fig. 11).

Rod-shaped nanoparticles and acicular nanoparticles are not strictly distinguished, and the morphology of the nano-hydroxyapatite is between that of the acicular nanoparticles and that of the rod-shaped nanoparticles. However, there are significant differences between these two morphologies and the platelet shape.

It has been surprisingly found that the addition of plate-like hydroxyapatite particles to an oral care composition results in an oral care composition having better remineralisation properties than other types of hydroxyapatite (rod or needle-like). That is, the oral care composition of the present invention significantly reduces re-exposure after occlusion of the dental tubules and the fluorine in the composition is more stable.

In certain embodiments of the invention, the plate-like hydroxyapatite comprises between 0.01% and 50%, or between 0.01% and 40%, or between 0.01% and 30%, or between 0.01% and 20%, or between 0.01% and 10%, or between 0.01% and 5%, or between 0.1% and 50%, or between 0.1% and 40%, or between 0.1% and 30%, or between 0.1% and 20%, or between 0.1% and 10%, or between 0.1% and 5%, or between 1% and 50%, or between 1% and 40%, or between 1% and 30%, or between 1% and 20%, or between 1% and 10%, or between 1% and 5% by weight of the oral care composition.

In certain embodiments of the present invention, the oral care composition further comprises a polycarboxyl compound.

"polycarboxyl compound" means in the present application a compound having at least two carboxyl groups, or more preferably three or more carboxyl groups in the chemical structural formula. The polycarboxyl compound ionizes the polycarboxylates when dissolved in water.

In certain embodiments of the present invention, the polycarboxyl compound is present in an amount of 0.01% to 10%, or 0.01% to 8%, or 0.01% to 6%, or 0.01% to 4%, or 0.01% to 2%, or 0.1% to 10%, or 0.1% to 8%, or 0.1% to 6%, or 0.1% to 4%, or 0.1% to 2%, or 0.1% to 1%, or 1% to 10%, or 1% to 8%, or 1% to 6%, or 1% to 4%, or 1% to 2% by weight of the oral care composition.

In certain embodiments of the present invention, the polycarboxyl compound is a citrate compound, i.e., a compound that ionizes citrate when dissolved in water.

In certain preferred embodiments of the invention, the citrate compound is a citrate salt, such as potassium citrate or sodium citrate.

In certain embodiments of the invention, the polycarboxyl compound is a polyaspartate, such as sodium polyaspartate (e.g., molecular weight 3000-.

In certain embodiments of the invention, the polycarboxyl compound is a 2-phosphonobutane-1, 2, 4-tricarboxylate salt, such as tetrasodium 2-phosphonobutane-1, 2, 4-tricarboxylate (PBTCA Na)₄)；

In certain embodiments of the invention, the polycarboxyl compound is an iminodisuccinate salt, such as sodium iminodisuccinate, potassium iminodisuccinate.

In certain embodiments of the invention, the polycarboxyl compound is a polyacrylate, such as sodium polyacrylate (e.g., molecular weight 3000-.

In certain preferred embodiments of the present invention, the polycarboxyl compound has the structure:

in certain embodiments of the present invention, the oral care composition further comprises a fluoride ion source.

In some embodiments of the invention, the fluoride ion source provides 100-2000ppm elemental fluorine; more preferably, 500-1500ppm of elemental fluorine is provided, most preferably 900-1450 ppm.

In certain embodiments of the invention, the fluoride ion source comprises sodium fluoride, potassium fluoride, calcium fluoride, magnesium fluoride, stannous fluoride, ammonium fluoride, sodium monofluorophosphate, potassium monofluorophosphate, fluorosilicate, olaflur.

In certain embodiments of the present invention, the oral care composition comprises a toothpaste, gel, mouthwash, or tooth powder.

The "orally acceptable carrier" of the present invention refers to any vehicle suitable for formulating the oral care compositions disclosed herein; (ii) is not harmful to the mammal when the orally acceptable carrier is retained in the mouth in the amounts disclosed herein without swallowing for a period of time sufficient to allow effective contact with the tooth surface as required by the present invention; overall, an orally acceptable carrier is not harmful if not intentionally swallowed; suitable orally acceptable carriers include, for example, one or more of the following: water, thickeners, buffers, humectants, surfactants, abrasives, sweeteners, flavoring agents, visual aids (e.g., colors, dyes, or mixtures thereof), anti-caries agents, antibacterial agents, whitening agents, desensitizing agents, vitamins, preservatives, enzymes, mixtures thereof, and the like.

According to certain embodiments of the present application, the oral care composition further comprises an adjunct such as a humectant, a flavoring agent, and/or a thickening agent.

"humectants" are ingredients that prevent the oral care composition from becoming dehydrated and hardened. Exemplary humectants include, but are not limited to, glycerin, propylene glycol, sorbitol, and the like. The humectant is typically present in the oral care composition in an amount of 10 to 80% by mass.

A "thickener" is a substance that increases the viscosity of a solution or liquid/solid mixture, but does not substantially change its properties. The purpose of the thickener is to provide skeleton, flow and stability to the product. Exemplary thickening agents include, but are not limited to, one or more of hydroxyethylcellulose, carboxymethylcellulose and salts thereof (e.g., sodium carboxymethylcellulose), carrageenan (carrageenan), carboxyvinyl polymers, xanthan gum (xanthan g μm), carrageenan, gelatin, pullulan, sodium alginate, and the like. In certain embodiments, the thickening agent comprises one or more of xanthan gum, carrageenan, or sodium carboxymethyl cellulose. The proportion by weight of thickener in the oral care composition is typically from 0.2 to 2%.

According to certain preferred embodiments of the present application, the oral care composition may further comprise active ingredients such as antibacterial agents, anticaries agents, anti-sensitivity agents, and/or whitening agents.

By "antibacterial agent" is meant a chemical substance that is capable of maintaining the growth or reproduction of certain microorganisms in an oral care composition below a necessary level over a period of time. Exemplary antimicrobial agents include, but are not limited to: stannous chloride, tetrahydrocurcumin, cetylpyridinium chloride, triclosan, and the like.

"anticaries agent" means a substance having an inhibitory effect on caries, for example, a substance which enhances the anticaries ability of teeth by decreasing the solubility of enamel hydroxyapatite, or a substance which controls plaque, inhibiting bacterial growth. Exemplary anticaries agents include, but are not limited to, phosphorus-containing agents (calcium phosphate, magnesium glycerophosphate, calcium lactate phosphate, sodium caseinate, etc.), or arginine and its derivatives.

An "anti-sensitivity agent" refers to a substance that prevents or treats dentinal hypersensitivity by inhibiting nerve impulses or being capable of closing or decreasing the permeability of dentinal tubules. Exemplary anti-sensitivity agents include, but are not limited to: potassium ion sources such as dipotassium glycyrrhizinate, potassium fluoride, potassium nitrate, potassium chloride and the like.

The "whitening agent" refers to a substance having a whitening effect on teeth. Exemplary whitening agents include, but are not limited to: a peroxide bleaching agent.

Application of the oral care composition of the present invention to the teeth detection method:

1. artificial saliva preparation

20mM HEPES,16mM KCl,1mM CaCl₂.2H₂O,4mM KH₂PO₄,4.5mM NH₄Cl,0.2mMMgCl₂6H2O, pH 7.0 adjusted with 1mol/L KOH solution. (weighing 4.766g HEPES, 1.1928g KCl,0.14701gCaCl₂.2H₂O,0.54436g KH₂PO4,0.2407g NH₄Cl,0.04066g MgCl₂.6H2O)

2. Procedure of experiment

Preparing dentin sections of 6mm by 2mm, polishing with water-milled silicon carbide abrasive paper of 400# and 2500# until the mirror surface is smooth, ultrasonically cleaning for 15min, acid etching for 5min with 6% citric acid, ultrasonically cleaning for 15min, selecting dentin with completely opened dentinal tubules under a metallographic microscope, and ultrasonically treating for 3 times, wherein each time lasts for 15min for later use;

1) brushing teeth with an electric toothbrush for 2min, washing with deionized water, and adding into artificial saliva for 6h (5 mL artificial saliva per dentin sample); the toothpaste was used repeatedly to brush the teeth, and the artificial saliva (5 mL of artificial saliva per sample) was added after rinsing with deionized water for 18 h. The cycle was repeated for 7 days, and dentin was removed from the artificial saliva on the 8 th morning and brushed with an electric toothbrush for 2min (without toothpaste) to remove loose structure from the dentin surface, and after drying Scanning Electron Microscopy (SEM) images were tested.

2) Brushing teeth with an electric toothbrush for 2min, washing with deionized water, and adding into artificial saliva for 6h (5 mL artificial saliva per dentin sample); the toothpaste was used repeatedly to brush the teeth, and the artificial saliva (5 mL of artificial saliva per sample) was added after rinsing with deionized water for 18 h. The circulation is carried out for 7 days. Then, deionized water is used for replacing toothpaste to brush teeth for 7 days, the teeth are brushed for 2 times every day, and dentin samples in the gaps between teeth brushing are placed in the deionized water; then, the sample was taken out of deionized water, rinsed clean, dried and tested for SEM.

3) Brushing teeth with an electric toothbrush for 2min, washing with deionized water, and adding into artificial saliva for 6h (5 mL artificial saliva per dentin sample); the toothpaste was used repeatedly to brush the teeth, and the artificial saliva (5 mL of artificial saliva per sample) was added after rinsing with deionized water for 18 h. The cycle was continued for 3 days and the dentin was removed from the artificial saliva on the morning of day 4 and brushed with an electric toothbrush for 2min (without toothpaste) to remove loose structure from the dentin surface and tested for SEM after drying.