Compositions comprising at least one chondroitin sulfate and at least one hydrophilic particulate matter and uses thereof

Abstract

Compositions comprising chondroitin sulfate and hydrophilic particulates and uses thereof are provided. Wherein the composition comprises the following components: (a) at least one hydrophilic particulate matter; and (b) at least one chondroitin sulfate, the average sphericity (Cir) and the average particle size (D) of the component (a) satisfying the following relationship: Cir < = k * D + B, where k =-0.001727, B = 0.92, the average particle size (D) in [mu] m, the average particle size of the component (a) being greater than 5 [mu] m and less than 280 [mu] m. The composition disclosed by the invention can be used for effectively sealing dentinal tubules; furthermore, the dentinal tubules sealed by the composition disclosed by the invention can maintain a relatively good sealing rate even if the dentinal tubules are stimulated by acid and the like.

Description

Technical Field

[0001] The present application belongs to the field of oral care technology, and specifically relates to a composition comprising at least one chondroitin sulfate and at least one hydrophilic particle and a use thereof. Background Art

[0002] Tooth sensitivity is a pain point for a considerable number of consumers. The reason is that the loss of tooth enamel leads to the exposure of dentinal tubules, which allows irritating foods to directly stimulate the dental nerves through the dentinal tubules. In order to alleviate tooth sensitivity, the oral care industry has developed a variety of repair technologies based on the mechanism of closing dentinal tubules, such as desensitizing toothpaste containing potassium nitrate; mineral deposition toothpaste containing fluoride and calcium; particle deposition toothpaste containing hydroxyapatite, etc.

[0003] However, the durability of the existing technology for sealing dentinal tubules is poor, especially after stimulation by acidic food, the sealant will fall off from the dentinal tubule port, resulting in re-exposure of the dentinal tubules. Summary of the invention

[0004] In view of the technical problems existing in the prior art, the present application provides a composition comprising at least one chondroitin sulfate and at least one hydrophilic particle. The composition can effectively seal the dentinal tubules after acting on the teeth, and can maintain a good sealing rate even after encountering stimulation such as acid, thereby solving the problem that the sealant in the prior art is easy to fall off from the dentinal tubules.

[0005] Specifically, this application involves the following aspects:

[0006] 1. An oral care composition comprising the following components:

[0007] (a) at least one hydrophilic particulate material; and

[0008] (b) at least one chondroitin sulfate,

[0009] The average sphericity (Cir) and average particle size (D) of the component (a) satisfy the following relationship:

[0010] Cir≤k*D+B

[0011] Wherein, k=-0.001727, B=0.92, and the average particle size (D) is in μm.

[0012] 2. The composition according to item 1, wherein the average particle size of component (a) is greater than 5 μm and less than 280 μm.

[0013] 3. The composition according to item 1 or 2, wherein the component (a) comprises one or more of silicon dioxide and a poorly soluble calcium salt.

[0014] 4. The composition according to item 1 or 2, wherein the content of the component (a) is greater than the content of the component (b).

[0015] 5. The composition according to item 4, wherein the content of component (a) is 5%-35% by mass in the composition.

[0016] 6. The composition according to item 4, wherein the content of component (b) is 0.5%-15% by mass in the composition.

[0017] 7. The composition according to any one of items 1 to 6, further comprising one or more orally acceptable carriers.

[0018] 8. Use of the composition according to any one of items 1 to 6 for preparing a product for sealing dentinal tubules.

[0019] 9. Use of the composition according to any one of items 1 to 6 in the preparation of a product for preventing / alleviating tooth sensitivity.

[0020] 10. The use according to item 8 or 9, wherein the product is a dentifrice product.

[0021] Effects of the Invention

[0022] The composition of the present application can effectively seal the dentinal tubules;

[0023] Furthermore, the dentinal tubules sealed by the composition of the present application can maintain a good sealing rate even after encountering stimulation such as acid. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 A schematic diagram of brushing teeth using a toothbrush device;

[0025] Figure 2 A schematic diagram of etching using an etching device;

[0026] Figure 3 (a) is a scanning electron microscopic image of dentinal tubules in a control area of ​​teeth brushed with the toothpaste sample of Example 2; Figure 3 (b) is a scanning electron microscopic image of dentinal tubules in the brushing area of ​​the toothbrush brushed with the toothpaste sample of Example 2; Figure 3 (c) is a scanning electron microscopic image of dentinal tubules after acid etching in the brushing area of ​​the toothpaste sample of Example 2;

[0027] Figure 4 (a) is a scanning electron microscopic image of dentinal tubules in a control area of ​​teeth brushed with the toothpaste sample of Example 8; Figure 4 (b) is a scanning electron microscopic image of dentinal tubules in the brushing area of ​​the toothpaste sample of Example 8; Figure 4 (c) is a scanning electron microscopic image of dentinal tubules after acid etching in the brushing area of ​​the toothpaste sample of Example 8;

[0028] Figure 5 (a) is a scanning electron micrograph of dentinal tubules in a control area after brushing teeth using the toothpaste sample of Comparative Example 1; Figure 5 (b) is a scanning electron microscope image of the dentinal tubules in the brushing area of ​​the toothpaste sample of Comparative Example 1; Figure 5 (c) is a scanning electron micrograph of dentinal tubules after acid etching in the brushing area of ​​the toothpaste sample of the comparative example. DETAILED DESCRIPTION

[0029] The present application is further described below in conjunction with examples. It should be understood that the examples are only used to further describe and illustrate the present application and are not used to limit the present application.

[0030] Unless otherwise defined, the technical and scientific terms in this specification have the same meaning as those generally understood by those skilled in the art. Although similar or identical methods and materials as described herein may be used in experiments or practical applications, materials and methods are described herein below. In the event of a conflict, the present specification including the definitions therein shall prevail. In addition, materials, methods and examples are provided for illustration only and are not restrictive. The present application is further described below in conjunction with specific embodiments, but is not intended to limit the scope of the present application.

[0031] In view of the problems existing in the prior art, the present application provides an oral care composition, comprising the following components:

[0032] (a) at least one hydrophilic particulate material; and

[0033] (b) at least one chondroitin sulfate,

[0034] The average sphericity (Cir) and average particle size (D) of the component (a) satisfy the following relationship:

[0035] Cir≤k*D+B

[0036] Wherein, k=-0.001727, B=0.92, and the average particle size (D) is in μm.

[0037] In the present application, the average sphericity (Cir), average particle size (D) and hydrophilicity of the particles can be detected by methods known in the art.

[0038] In some embodiments, the average sphericity (Cir) of the particles can be obtained by photographing the particles with a scanning electron microscope (SEM), and then analyzing the photograph to obtain sphericity data. Specifically, the particles are photographed with a scanning electron microscope (SEM), and then the photographs are analyzed using Image J image processing software (or equivalent software), and a plurality of (e.g., 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200 or more) non-aggregated particle images are randomly selected, and their projected area (Area) on the observation surface and the perimeter (P) of the projected shape are calculated, and the sphericity Cir is calculated according to the following formula:

[0039] Cir=4π*[Area] / [P] 2

[0040] The Cir data of multiple particles are arithmetic averaged to obtain the average sphericity of the particles.

[0041] The average particle size can be measured by conventional measurement methods in the art, such as laser method, sieving method, sedimentation method, etc.

[0042] In some embodiments, the average particle size (D) of the particles can be photographed using a camera system, and then the photos are analyzed to obtain the particle size data. Specifically, Camzier X2 is used to photograph at least 50 (e.g., 50, 60, 70, 80, 90, 100, 200 or more) non-aggregated particles under controlled optical conditions using a high-resolution camera system to generate photos, and then the captured particle images are processed, analyzed and calculated using its built-in software to obtain the particle size of the particles. During the analysis, the particle size measured is statistically calculated to generate a particle size distribution diagram, and the median particle size D50 is taken as the average particle size of the particles.

[0043] In some embodiments, the hydrophilicity of the particles refers to the ability of the particles to attract water molecules. Hydrophilicity can be measured by measuring the sedimentation rate of the particles in water. When the sedimentation rate of the particles is greater than or equal to 50%, the particles are considered to be hydrophilic; otherwise, the particles are considered to be water-repellent. The sedimentation rate of the particles can be determined by dispersing a certain number of particles in water and calculating the percentage of particles that settle within a certain period of time. Specifically, 1g of the particles can be accurately weighed and transferred to a beaker containing 100g of deionized water. Use a magnetic stirrer to stir the suspension at a speed of 300rpm for 5 minutes. After the stirring is completed, let it stand for 1 minute, then use a metal screen with a mesh size of more than 150 to scoop out the particles floating on the water surface, dry them and weigh them, so that the sedimentation rate of the particles can be calculated.

[0044] In the present application, hydrophilic particles are substances that can attract water molecules but are insoluble or poorly soluble in water.

[0045] The average particle size of the component (a) is greater than 5 μm and less than 280 μm, for example, it can be 5.1 μm, 6 μm, 10 μm, 20 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, 100 μm, 110 μm, 120 μm, 130 μm, 140 μm, 150 μm, 160 μm, 170 μm, 180 μm, 190 μm, 200 μm, 210 μm, 220 μm, 230 μm, 240 μm, 250 μm, 260 μm, 270 μm, 279 μm, etc., and any values ​​between these values.

[0046] In some embodiments, the component (a) includes at least one or more of silicon dioxide and a sparingly soluble calcium salt.

[0047] More specifically, the poorly soluble calcium salt includes one or more of calcium hydrogen phosphate, calcium pyrophosphate, and calcium carbonate.

[0048] In some embodiments, the molecular weight of component (b) is 8-40kDa, for example, it can be 8kDa, 9kDa, 10kDa, 11kDa, 12kDa, 13kDa, 14kDa, 15kDa, 16kDa, 17kDa, 18kDa, 19kDa, 20kDa, 21kDa, 22kDa, 23kDa, 24kDa, 25kDa, 26kDa, 27kDa, 28kDa, 29kDa, 30kDa, 31kDa, 32kDa, 33kDa, 34kDa, 35kDa, 36kDa, 37kDa, 38kDa, 39kDa, 40kDa, and any value between these values.

[0049] In the present application, the molecular weight of the component (b) refers to the weight average molecular weight of chondroitin sulfate.

[0050] The weight average molecular weight is the statistical average molecular weight by mass, which is the molecular weight averaged over a unit weight and can be measured by conventional measurement methods in the art, such as high performance liquid chromatography (HPLC), gel permeation chromatography (GPC), light scattering, and the like.

[0051] In some embodiments, the content of component (a) is greater than the content of component (b).

[0052] In some embodiments, the content of component (a) is 5%-35% by mass percentage in the composition, for example, it can be 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, and any value therebetween.

[0053] In some embodiments, the content of component (b) is 0.5%-15% by mass in the composition, for example, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, and any value therebetween.

[0054] In some embodiments, the oral care composition comprises the following components:

[0055] (a) at least one hydrophilic particulate material; and

[0056] (b) at least one chondroitin sulfate,

[0057] The average sphericity (Cir) and average particle size (D) of the component (a) satisfy the following relationship:

[0058] Cir≤k*D+B

[0059] Wherein, k=-0.001727, B=0.92, and the average particle size (D) is in μm.

[0060] The average particle size of the component (a) is greater than 5 μm and less than 280 μm.

[0061] The component (a) includes at least one or more of silicon dioxide and a sparingly soluble calcium salt.

[0062] More specifically, the poorly soluble calcium salt includes one or more of calcium hydrogen phosphate, calcium pyrophosphate, and calcium carbonate.

[0063] The content of the component (a) is greater than that of the component (b), wherein the content of the component (a) is 5%-35%, and the content of the component (b) is 0.5%-15%.

[0064] Furthermore, the oral care composition may further include one or more orally acceptable carriers.

[0065] In some specific embodiments, the composition may further include fluoride ions, a pH adjuster, a thickener, an abrasive, a wetting agent, a foaming agent, and the like.

[0066] In the present application, there is no limitation on fluoride ions, pH regulators, thickeners, abrasives, wetting agents, and foaming agents, and those skilled in the art can make routine selections based on actual needs.

[0067] As the fluoride ion, as the anti-caries agent, for example, sodium fluoride, potassium fluoride, sodium monofluorophosphate, etc. can be mentioned.

[0068] Examples of pH adjusters include organic acids or bases derived from nature or obtained by microbial fermentation or chemical synthesis, such as tartaric acid, lactic acid, hydrochloric acid, calcium hydroxide, potassium hydroxide, sodium bicarbonate, and the like.

[0069] As the thickener, the particles are exemplified, for example, xanthan gum, gum arabic, carrageenan, carboxymethyl cellulose, hydroxypropyl cellulose, starch, modified starch and the like.

[0070] Examples of the abrasive include calcium silicate, aluminum silicate, aluminum oxide, aluminum hydroxide, alumina, zeolite, titanium oxide, and zirconium silicate.

[0071] Examples of the wetting agent include glycerin, polyethylene glycol, sorbitol, xylitol, ethylene glycol, 1,3-butylene glycol, and propylene glycol.

[0072] Examples of the foaming agent include sodium lauryl sulfate and lauroyl sarcosine.

[0073] Flavors, flavoring agents, sweeteners, coloring agents, etc. may also be added.

[0074] The oral care composition of the present application includes hydrophilic particles whose sphericity and particle size satisfy a specific relationship, and chondroitin sulfate. The oral care composition can effectively seal the dentinal tubules after acting on the teeth, and can maintain a good sealing rate even after encountering stimulation such as acid, thereby solving the problem of the prior art that the sealant is easy to fall off from the dentinal tubules.

[0075] The present application provides use of the above-mentioned composition in preparing a product for sealing dentinal tubules.

[0076] Dentin is a hard tissue that constitutes the main body of teeth. It is located in the inner layer of enamel and cementum, and is also the side wall of the pulp cavity and root canal. It is light yellow in color, contains about 30% organic matter and water, 70% inorganic matter, and has a lower hardness than enamel. If observed under a microscope, it can be seen that there are many regularly arranged thin tubes in the dentin, called dentinal tubules, which contain nerve fibers. When the dentin is exposed, it can sense external stimuli such as cold, heat, acid, and sweet, causing pain. Therefore, sealing the dentinal tubules can isolate external stimuli such as cold, heat, acid, and sweet, and prevent / relieve tooth sensitivity.

[0077] The present application provides use of the above-mentioned composition in preparing a product for preventing / alleviating tooth sensitivity.

[0078] Regarding the product for sealing the dentinal tubules, the present application does not impose any restriction on its type, as long as it has the function of sealing the dentinal tubules.

[0079] In some embodiments, the product is a tooth cleaning product, including toothpaste, tooth powder or tooth gel.

[0080] Example

[0081] The raw materials, reagents and equipment used in the examples of this application are shown in the following table.

[0082]

[0083]

[0084]

[0085] (1) Water repellency test of particles

[0086] 1 g of the particles were accurately weighed and transferred into a beaker containing 100 g of deionized water. The suspension was stirred at 300 rpm using a magnetic stirrer for 5 minutes.

[0087] After stirring, let it stand for 1 minute, then use a metal screen with a mesh size of 150 or more to scoop out the particles floating on the water surface, dry them, and weigh them. The percentage of settled particles (i.e., the particle sedimentation rate) can be calculated. When the percentage is greater than or equal to 50%, the particles are considered hydrophilic; otherwise, the particles are considered water-repellent.

[0088] (2) Particle sphericity and particle size test

[0089] The particles were photographed using a scanning electron microscope (SEM), and then the photos were analyzed to obtain the data on the sphericity of the particles. During the analysis, 50 non-aggregated particle images were randomly selected using Image J image processing software (or equivalent software), and their projected area (Area) and perimeter (P) of the projected shape on the observation surface were calculated, and the sphericity Cir was calculated according to the following formula:

[0090] Cir=4π*[Area] / [P] 2

[0091] The 50 data points were averaged to obtain the average sphericity of the particles.

[0092] Camzier X2 uses a high-resolution camera system to take at least 50 non-aggregated particles under controlled optical conditions to generate photos, and then uses its built-in software to process, analyze and calculate the captured particle images to obtain the particle size. During the analysis, the measured particle size is statistically measured to generate a particle size distribution diagram, and the median particle size D50 is taken as the average particle size of the particles.

[0093] (3) Preparation method of toothpaste samples

[0094] Premixing of grinding phase: put the granules into the powder bin according to the formula amount, stir and shake to form the grinding phase for later use;

[0095] Premixing of aqueous phase: Add chondroitin sulfate into pre-measured deionized water according to the formula amount, stir until completely dissolved, and form an aqueous phase for standby use;

[0096] Premixing of hydrophilic colloid: Add carrageenan and xanthan gum to the pre-measured glycerin in order according to the formula, stir and disperse evenly to form a hydrophilic colloid phase for later use;

[0097] Premixing of flavors: Add BIO-201 bioglycolipid to the pre-measured flavors according to the formula, stir and disperse to form a flavor phase for later use;

[0098] Paste making process: add sorbitol to the water phase according to the formula amount, stir and homogenize until mixed evenly; add the grinding phase, evacuate the vacuum, and stir until mixed evenly; add the hydrophilic colloid phase, evacuate the vacuum, and stir and homogenize until mixed evenly; add the flavor phase, evacuate the vacuum, and stir and homogenize until mixed evenly; after degassing, inspect and discharge the material after meeting the internal control standards.

[0099] (4) Pretreatment methods of cattle teeth

[0100] Take the prepared bovine tooth slices, place them in a pre-sterilized beaker, add deionized water to cover them, and soak for 10 minutes. Pour out the deionized water, and repeat the operation 3 times.

[0101] Prepare a 10% phosphoric acid solution as a tooth treatment solution;

[0102] The bovine teeth were immersed in the tooth treatment solution for 15 min, then taken out, rinsed with deionized water, and then immersed in deionized water for 10 min before being taken out;

[0103] The tooth samples were placed in an environment of 25°C and 5% RH for drying for 6 h;

[0104] A protective layer of light-curable resin was applied on the surface of half of the bovine tooth and cured using a light-curing machine to maintain the original morphology of the exposed tubules in this part as a comparison area.

[0105] (5) Toothbrushing test method

[0106] Take 80g of toothpaste sample, add 40g of oral simulation liquid m-SBF and 40g of ionized water, stir and disperse evenly to form toothpaste slurry, and set aside;

[0107] Place the toothbrush in deionized water and soak it for 30 minutes before use.

[0108] like Figure 1 As shown, the tooth sample in (4) is fixed on an acrylic plate, the acrylic plate is placed in a toothbrush machine, and the toothbrush is fixed on the toothbrush machine;

[0109] Inject toothpaste slurry into the brush cup of the toothbrush machine and adjust the height of the brush cup to ensure that the slurry can completely immerse the teeth and the toothbrush head;

[0110] Start the toothbrushing process and set the time to 3 minutes. After brushing, take out the teeth, rinse them with deionized water, and let them air dry naturally;

[0111] Remove the protective layer of light-cured resin from the tooth contrast area and set aside.

[0112] (6) Corrosion test method

[0113] like Figure 2 As shown, take the new tooth sample that has completed the photoprotective resin curing in step (4) and fix it on the acrylic plate, then place the acrylic plate on the iron stand platform, complete the brushing step in (5), and then fix the burette filled with cola on the iron stand, with the lower tube mouth of the burette facing the cow's teeth at a height of 1 cm; drip cola on the cow's teeth at a speed of 1 ml / s for 10 seconds.

[0114] Then, rinse with deionized water and air dry naturally to remove the protective layer of light-cured resin on the tooth comparison area for standby use.

[0115] (7) Calculation of tubule closure retention rate

[0116] The tooth samples were gold-sputtered using an ion sputtering apparatus, and then the number and distribution of dental tubules were observed using a scanning electron microscope.

[0117] Dentin tubule closure rate after brushing = abs (1-total area of ​​dentinal tubules in brushing area / total area of ​​dentinal tubules in control area) * 100%

[0118] Dentin tubule closure rate after acid etching = abs (1-total area of ​​dentinal tubules after acid etching in brushing area / total area of ​​dentinal tubules in control area) * 100%

[0119] Sealing retention rate = dentinal tubule sealing rate after acid etching / dentinal tubule sealing rate after toothbrushing * 100%

[0120] Here, abs represents absolute value.

[0121] Specifically, the particle information and toothpaste formula used in each embodiment and comparative example are shown in Table 1.

[0122] Table 1

[0123]

[0124]

[0125]

[0126] Wherein Cir is the average sphericity of the particles measured in step (2), D is the average particle size of the particles (micrometers), k=-0.001727, and B=0.92.

[0127] Scanning electron microscopy images of dentinal tubules before and after treatment with the toothpaste of Example 2 are as follows Figure 3 (a)-(c) show scanning electron microscopy images of dentinal tubules before and after treatment with the toothpaste of Example 8. Figure 4 As shown in (a)-(c), the scanning electron microscopy images of the dentinal tubules before and after treatment with the toothpaste of Comparative Example 1 are as follows Figure 5 As shown in (a)-(c), the dentinal tubule sealing rate and sealing retention rate measured in each embodiment and comparative example are shown in Table 2.

[0128] Table 2

[0129] NO. Dentin tubule closure rate after toothbrushing Closure retention rate Example 1 90％ 50％ Example 2 95％ 70％ Example 3 95％ 90％ Example 4 90％ 50％ Example 5 90％ 55％ Example 6 85％ 70％ Example 7 95％ 70％ Example 8 95％ 55％ Example 9 90％ 60％ Example 10 90％ 65％ Embodiment 11 85％ 60％ Example 12 95％ 70％ Embodiment 13 91％ 50％ Comparative Example 1 90％ 15％ Comparative Example 2 90％ 15％ Comparative Example 3 90％ 15％ Comparative Example 4 90％ 10％ Comparative Example 5 85％ 10％ Comparative Example 6 85％ 15％ Comparative Example 7 90％ 5％ Comparative Example 8 90％ 10％ Comparative Example 9 60％ 10％ Comparative Example 10 50％ 10％ Comparative Example 11 60％ 25％ Comparative Example 12 96％ 27％ Comparative Example 13 99％ 22％ Comparative Example 14 95％ 29％

[0130] The above results indicate that the embodiments of the present application can effectively seal the dentinal tubules, and after acid corrosion, a relatively high sealing rate of the dentinal tubules can still be obtained.

Claims

1. An oral care composition comprising the following components: (a) at least one hydrophilic particulate material; and (b) at least one chondroitin sulfate, The average sphericity (Cir) and average particle size (D) of the component (a) satisfy the following relationship: Cir≤k*D+B in, k=-0.001727, B=0.92, average particle size (D) in μm. 2 . The composition according to claim 1 , wherein the average particle size of the component (a) is greater than 5 μm and less than 280 μm.

3. The composition according to claim 1 or 2, wherein the component (a) comprises one or more of silicon dioxide and a sparingly soluble calcium salt.

4. The composition according to claim 1 or 2, wherein The content of the component (a) is greater than the content of the component (b).

5. The composition according to claim 4, wherein the content of component (a) is 5%-35% by mass percentage in the composition.

6. The composition according to claim 4, wherein the content of component (b) is 0.5%-15% by mass percentage in the composition.

7. The composition of any one of claims 1-6, further comprising one or more orally acceptable carriers.

8. Use of the composition according to any one of claims 1 to 6 in preparing a product for sealing dentinal tubules.

9. Use of the composition according to any one of claims 1 to 6 in preparing a product for preventing / alleviating tooth sensitivity.

10. The use according to claim 8 or 9, wherein the product is a tooth cleaning product.

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