Oral composition containing metaphosphate

Abstract

[Problem] To provide an oral composition that contains high concentrations of fluorine and hinokitiol while achieving stabilization of hinokitiol. [Solution] An oral composition containing a fluorine compound, hinokitiol, and a metaphosphate, wherein the fluorine content is 1000 ppm or more.

Description

Oral composition containing a metaphosphate salt

[0001] The present disclosure relates to an oral composition that contains hinokitiol and a high concentration of fluorine, while allowing the hinokitiol to exist stably.

[0002] Conventionally, bactericides have been blended into oral compositions such as dentifrices and mouthwashes to reduce the number of pathogenic bacteria causing dental caries or periodontal disease. Various bactericides to be blended in oral compositions are known, and hinokitiol is widely used in oral compositions due to its low toxicity and broad antibacterial spectrum (Patent Document 1).

[0003] In addition, for the prevention of dental caries, the use of dentifrices containing fluorine compounds is recommended as a daily self-care practice. Fluorine compounds impart resistance to acid produced by cariogenic bacteria to teeth, repair initial caries through remineralization, and restore the original healthy tooth structure, and thus are widely used in oral compositions. Furthermore, fluorine compounds also have an effect of suppressing the proliferation of cariogenic bacteria (Patent Document 2).

[0004] Japanese Patent Application Laid-Open No. 2017-007991 Japanese Patent Application Laid-Open No. 2021-107362

[0005] The present inventor studied the storage stability of hinokitiol in the formulation of an oral composition containing a fluorine compound and hinokitiol. The present inventor found that when fluorine is contained in the oral composition at a general concentration, hinokitiol is stably stored in the oral composition, but when fluorine is contained at a high concentration, the inventor faced the problem that hinokitiol becomes unstable in the oral composition. The destabilization of hinokitiol reduces the bactericidal effect of the oral composition, and thus is an important problem that must be solved.

[0006] Accordingly, an object of the present disclosure is to provide an oral composition that contains a high concentration of fluorine and hinokitiol, while achieving stabilization of hinokitiol.

[0007] In order to achieve the above object, there is provided an oral composition comprising a fluorine compound, hinokitiol, and a metaphosphate salt, wherein the fluorine content is 1000 ppm or more.

[0008] According to this disclosure, it is possible to provide an oral composition that contains a high concentration of fluorine and hinokitiol while achieving hinokitiol stabilization. The oral composition can exhibit a bactericidal effect due to hinokitiol and a caries-preventive effect due to the high concentration of fluorine, and the problem of hinokitiol destabilization caused by the high concentration of fluorine (particularly under high temperature conditions) is solved by the metaphosphate.

[0009] 1. Oral Composition of the Disclosure The Disclosure provides an oral composition comprising a fluorine compound, hinokitiol, and a metaphosphate, wherein the fluorine content is 1000 ppm or more (the oral composition of the Disclosure).

[0010] (Fluorine compounds) The oral compositions of this disclosure contain fluorine compounds.

[0011] In the oral compositions of this disclosure, the fluorine compound is a known component that imparts resistance to acids produced by cariogenic bacteria to teeth, has the effect of remineralizing early caries, and also has the effect of suppressing the growth of cariogenic bacteria. The fluorine compound used in the oral compositions of this disclosure is not particularly limited as long as it is applicable in the oral cavity, but examples include alkali metal fluorides, fluorophosphates, fluorophosphates, stannous fluoride, and silver diamine fluoride. The fluorine compound may be used alone or in combination of two or more. From the viewpoint of obtaining the above effects on caries significantly, the fluorine compound is preferably at least one selected from the group consisting of alkali metal fluorides, fluorophosphates, and fluorophosphates, and more preferably fluorophosphates.

[0012] The alkali metal fluoride is not particularly limited as long as it is applicable in the oral cavity, but examples include sodium fluoride and potassium fluoride. The alkali metal fluoride may be used alone or in combination of two or more types. Among the alkali metal fluorides exemplified above, sodium fluoride is preferred from the viewpoint of obtaining the above-mentioned effect on dental caries significantly.

[0013] The fluorophosphate is not particularly limited as long as it can be applied in the oral cavity, but examples include monofluorophosphate and difluorophosphate. The fluorophosphate may be used alone or in combination of two or more types. Among the fluorophosphates exemplified above, monofluorophosphate is preferred from the viewpoint of obtaining the above-mentioned effects on dental caries.

[0014] The fluorophosphate is not particularly limited as long as it is applicable in the oral cavity, but examples include alkali metal salts of fluorophosphate, specifically sodium salts and potassium salts of fluorophosphate. The fluorophosphate may be used alone or in combination of two or more types. Among the fluorophosphates exemplified above, sodium salts are preferred, and sodium monofluorophosphate is more preferred, from the viewpoint of obtaining the above-mentioned effects on dental caries.

[0015] In the oral composition of this disclosure, the fluorine content in the oral composition is 1000 ppm or more in order to impart the above-mentioned effect against dental caries. Although the oral composition of this disclosure contains a high concentration of fluorine of 1000 ppm or more, the destabilization of hinokitiol caused by the high concentration of fluorine (particularly the destabilization of hinokitiol under high temperature conditions) is suppressed because a metaphosphate salt, as described later, is included.

[0016] In the oral composition of this disclosure, the lower limit of the fluorine content in the oral composition is 1000 ppm or more, preferably 1100 ppm or more, more preferably 1200 ppm or more, even more preferably 1300 ppm or more, and even more preferably 1400 ppm or more, from the viewpoint of imparting the above-mentioned effects against dental caries. Since the oral composition of this disclosure contains a metaphosphate salt described later, even if the oral composition of this disclosure contains 1000 ppm or more of fluorine, the destabilization of hinokitiol can be suppressed. Furthermore, in the oral composition of this disclosure, there is no particular upper limit to the fluorine content in the oral composition, but for example, it is 1500 ppm or less.

[0017] In one embodiment of the oral composition of the present disclosure, when the fluorine compound is sodium monofluorophosphate, the content of sodium monofluorophosphate is, for example, 0.76 to 1.14% by weight, preferably 0.83 to 1.14% by weight, more preferably 0.91 to 1.14% by weight, even more preferably 0.99 to 1.13% by weight, and most preferably 1.06 to 1.14% by weight, from the viewpoint of imparting the above-mentioned effect against dental caries to the oral composition.

[0018] (Hinokitiol) The oral compositions of this disclosure contain hinokitiol.

[0019] In the oral compositions of this disclosure, hinokitiol is a known component incorporated into oral compositions as a disinfectant, etc. Hinokitiol may be derived from natural products or may be chemically synthesized. Furthermore, the hinokitiol used in this disclosure may be a refined product or a crude product. When using a refined product, for example, a hinokitiol-containing essential oil obtained from a tree may be used.

[0020] In the oral composition of this disclosure, the hinokitiol content is appropriately set according to the formulation form and use of the oral composition, but is, for example, 0.1 to 1 part by weight per 1 part by weight of fluorine. Furthermore, from the viewpoint of exhibiting excellent bactericidal activity and stabilizing the hinokitiol contained in the oral composition under high-temperature conditions, the hinokitiol content is, for example, 0.27 to 0.4 parts by weight, preferably 0.27 to 0.36 parts by weight, more preferably 0.27 to 0.33 parts by weight, even more preferably 0.27 to 0.31 parts by weight, and most preferably 0.27 to 0.29 parts by weight per 1 part by weight of fluorine.

[0021] In one embodiment of the oral composition of the present disclosure, when the fluorine compound is sodium monofluorophosphate, the hinokitiol content is, for example, 0.01 to 0.5 parts by weight per 1 part by weight of sodium monofluorophosphate. Furthermore, from the viewpoint of exhibiting excellent bactericidal activity and stabilizing the hinokitiol contained in the oral composition under high-temperature conditions, the hinokitiol content is, for example, 0.035 to 0.053 parts by weight, preferably 0.035 to 0.048 parts by weight, more preferably 0.035 to 0.044 parts by weight, even more preferably 0.035 to 0.041 parts by weight, and most preferably 0.035 to 0.038 parts by weight per 1 part by weight of sodium monofluorophosphate.

[0022] In the oral compositions of this disclosure, the hinokitiol content is appropriately set according to the formulation form and use of the oral composition, but is, for example, 0.005 to 1% by weight. Furthermore, from the viewpoint of exhibiting excellent bactericidal activity and stabilizing the hinokitiol contained in the oral composition under high-temperature conditions, the hinokitiol content is, for example, 0.01 to 0.5% by weight, preferably 0.02 to 0.3% by weight, more preferably 0.03 to 0.2% by weight, and even more preferably 0.04 to 0.1% by weight.

[0023] (Metaphosphate) The oral compositions of this disclosure contain metaphosphate.

[0024] In the oral composition of this disclosure, metaphosphates are incorporated into the oral composition to suppress the destabilization of hinokitiol contained in the oral composition under high-temperature conditions caused by high concentrations of fluorine. Therefore, it is inferred that metaphosphates have the function of inhibiting the reaction between fluorine compounds and hinokitiol.

[0025] In the oral compositions of this disclosure, examples of metaphosphates include alkali metal salts. Examples of alkali metal salts of metaphosphate include sodium metaphosphate and potassium metaphosphate, with sodium metaphosphate being preferred. The metaphosphate may be a solvate (e.g., a hydrate) or a solvate, and both are included. The metaphosphate may be used alone or in combination of two or more.

[0026] In the oral compositions of this disclosure, when two or more metaphosphates are included simultaneously, the mixing ratio is not particularly limited as long as it suppresses the destabilization of hinokitiol. For example, when two metaphosphates are included simultaneously, the mixing ratio (molar ratio) of the metaphosphates can be, for example, 1:10 to 10:1.

[0027] In the oral composition of this disclosure, the content of the metaphosphate needs to be appropriately adjusted according to the fluorine content in the oral composition. For example, when the metaphosphate is sodium metaphosphate, the content is, for example, 1.0 to 10 parts by weight per part by weight of fluorine. Furthermore, from the viewpoint of stabilizing the hinokitiol contained in the oral composition under high-temperature conditions, the content of sodium metaphosphate is, for example, 4.00 to 6.00 parts by weight, preferably 4.00 to 5.45 parts by weight, more preferably 4.00 to 5.00 parts by weight, even more preferably 4.00 to 4.62 parts by weight, and most preferably 4.00 to 4.29 parts by weight per part by weight of fluorine.

[0028] In one embodiment of the oral composition of the present disclosure, when the fluorine compound is sodium monofluorophosphate and the metaphosphate is sodium metaphosphate, the amount is, for example, 0.1 to 1.0 parts by weight per 1 part by weight of sodium monofluorophosphate. Furthermore, from the viewpoint of stabilizing hinokitiol contained in the oral composition under high-temperature conditions, the amount of sodium metaphosphate is, for example, 0.528 to 0.792 parts by weight, preferably 0.528 to 0.720 parts by weight, more preferably 0.528 to 0.660 parts by weight, even more preferably 0.528 to 0.609 parts by weight, and most preferably 0.528 to 0.565 parts by weight per 1 part by weight of sodium monofluorophosphate.

[0029] In the oral composition of this disclosure, the content of metaphosphate needs to be appropriately adjusted according to the content of fluorine compounds and hinokitiol in the oral composition, but is, for example, 0.1 to 10% by weight. Furthermore, from the viewpoint of stabilizing the hinokitiol contained in the oral composition under high-temperature conditions, the content of metaphosphate is, for example, 0.1 to 4% by weight, preferably 0.1 to 2% by weight, and more preferably 0.1 to 1% by weight.

[0030] (Dosage Form, Form of Use) In the oral compositions of this disclosure, the dosage form or form of use is not particularly limited as long as it can be applied to the oral cavity, but examples include liquid or semi-solid forms (e.g., gel, paste, etc.).

[0031] The dosage form or form of use of the oral composition of this disclosure is not particularly limited as long as it can be applied to the oral cavity and remain there for a certain period of time. Examples include oral hygiene agents such as liquid toothpaste, tooth paste, mouthwash (mouthwash is sometimes referred to as mouth rinse, mouthwash, dental rinse, etc.), oral fresheners (such as mouth spray), and oral ointment. Preferably, liquid toothpaste, tooth paste, and mouthwash are included.

[0032] The storage conditions for the oral composition of this disclosure are not particularly limited as long as the metaphosphate stabilizes the hinokitiol contained in the oral composition under high-temperature conditions, but for example, the storage temperature can be 0 to 70°C, preferably 0 to 60°C.

[0033] In addition to the components described above, the oral compositions of this disclosure may contain, depending on the form of the oral composition, components commonly used in the art, to the extent that they do not impair the effects of the pharmaceutical compositions of this disclosure, the bactericidal effect of hinokitiol, the caries prevention effect of fluorine compounds, and the stabilization effect of metaphosphates on hinokitiol under high-temperature conditions. Examples of components commonly used in the art include anti-inflammatory agents, antibacterial agents, hemostatic agents, hypersensitivity inhibitors, stabilizers, wetting agents, solubilizers, thickeners, abrasives, whitening agents, astringents, flavoring agents, detergents, pH adjusters, foaming agents, colorants, preservatives, bases, and cleaning agents.

[0034] Examples of anti-inflammatory agents include dipotassium glycyrrhizinate and β-glycyrrhetinic acid.

[0035] Examples of antibacterial agents include cetylpyridinium chloride.

[0036] Examples of hemostatic agents include ε-aminocaproic acid.

[0037] Examples of agents that suppress hypersensitivity include aluminum lactate.

[0038] Examples of stabilizers include DL-alanine, disodium edetate, titanium dioxide, and citric acid.

[0039] Examples of humectants include concentrated glycerin, PG, and sorbitol solution.

[0040] Examples of solubilizing agents include ethanol and polyoxyethylene hydrogenated castor oil.

[0041] Examples of thickening agents include carrageenan, anhydrous silicic acid, and sodium carboxymethylcellulose.

[0042] Examples of abrasives include hydrated silica and calcium pyrophosphate.

[0043] Examples of whitening agents include titanium dioxide.

[0044] Examples of astringents include Angelica root extract (1) and Peony root extract.

[0045] Examples of flavoring agents include sodium chloride, sodium saccharin and the like.

[0046] Examples of detergents include soapberry extract and the like.

[0047] Examples of pH adjusters include sodium hydroxide and the like.

[0048] Examples of foaming agents include sodium N-lauroyl-L-glutamate, sodium lauryl sulfate, alkyl glycosides and the like.

[0049] Examples of coloring agents include Yellow No. 203, Blue No. 1 and the like.

[0050] Examples of preservatives include ethyl parahydroxybenzoate, propyl parahydroxybenzoate, parabens and the like.

[0051] Examples of bases include purified water, sorbitol solution and the like.

[0052] Examples of cleaning agents include propyldimethyl octadecyl ammonium chloride-bonded silicic anhydride (Bionium) and the like.

[0053] 2. Method for producing the oral composition of the present disclosure (or method for stabilizing hinokitiol of the present disclosure) The present disclosure provides a method for producing an oral composition, comprising a step of mixing a fluorine compound, hinokitiol, and a metaphosphate, wherein the fluorine content in the oral composition is 1000 ppm or more, (the method for producing an oral composition of the present disclosure). The present disclosure also provides a method for stabilizing hinokitiol in an oral composition, comprising mixing a fluorine compound, hinokitiol, and a metaphosphate, wherein the fluorine content in the oral composition is 1000 ppm or more, (the method for stabilizing hinokitiol of the present disclosure).

[0054] In the method for producing the oral composition of the present disclosure (or the method for stabilizing hinokitiol of the present disclosure), the fluorine compound, hinokitiol, and metaphosphate may be the same as those described in the oral composition of the present disclosure.

[0055] A method for producing the oral composition of the present disclosure (or a method for stabilizing hinokitiol of the present disclosure) comprises the step of mixing a fluorine compound, hinokitiol, and a metaphosphate. The fluorine compound, hinokitiol, and metaphosphate may be mixed simultaneously, or (i) the fluorine compound and hinokitiol, (ii) the fluorine compound and metaphosphate, or (iii) hinokitiol and metaphosphate may be mixed beforehand and the remaining components mixed afterward.

[0056] Next, examples of the present disclosure will be described. However, the present disclosure is not limited to the following examples. Commercial reagents were used according to their respective protocols unless otherwise specified.

[0057] Example 1. Hinokitiol Stability Evaluation Test Samples of the compositions shown in Tables 1 and 2 were prepared. Specifically, each component shown in Tables 1 and 2 was mixed to prepare each liquid or paste-type toothpaste. 40 g of the liquid from Table 1, or approximately 40 g of the paste-type toothpaste from Table 2, was taken and filled into 40 g capacity tubes (tubes with laminated aluminum layers and light-shielding interiors), and stored at 4°C for two weeks. Another portion was stored at 60°C for two weeks. The remaining amount of hinokitiol in each liquid or paste-type toothpaste was measured by high-performance liquid chromatography under the following conditions.

[0058]

[0059]

[0060] <Test Conditions> Equipment used: High-performance liquid chromatograph LC-20AD (Shimadzu Corporation) Detector: Ultraviolet absorbance spectrophotometer - measurement wavelength 350 nm Column: ODS column, length 15 cm Column temperature: 40°C Mobile phase: EDTA + phosphate buffer / acetonitrile mixture Flow rate: 1.0 mL / min

[0061] Test Example 1 The stability of hinokitiol after storage of Reference Example 1, Comparative Examples 1 and 2, and Example 1, prepared above, was tested under the above conditions. When stored for two weeks at 60°C, the amount of hinokitiol remaining in Reference Example 1, which contained a low concentration of fluorine, was 90% or more compared to the amount of hinokitiol remaining after two weeks of storage at 4°C, indicating no stability issues. However, in Comparative Example 1, which contained a high concentration of fluorine, the amount of hinokitiol remaining fell to less than 90%, indicating instability. This instability could not be resolved even in Comparative Example 2, which added citric acid in addition to the high concentration of fluorine. On the other hand, in Example 1, which added sodium metaphosphate in addition to the high concentration of fluorine, the amount of hinokitiol remaining recovered to 90% or more compared to the amount of hinokitiol remaining after two weeks of storage at 4°C, indicating stable performance. The results are shown in Table 3.

[0062]

[0063] Test Example 2 The stability of hinokitiol after storage of Reference Example 2, Comparative Examples 3 and 4, and Example 2, prepared above, was tested under the above conditions. After storage for two weeks at 4°C and then for two weeks at 60°C, Reference Example 2, which contained a low concentration of fluorine, had a residual amount of hinokitiol of 90% or more (92.1%) (based on storage for two weeks at 4°C), indicating no stability issues. However, Comparative Example 3, which contained a high concentration of fluorine, had a residual amount of hinokitiol of less than 90% (88.7%) (based on storage for two weeks at 4°C), indicating instability. This instability could not be resolved even with Comparative Example 4, which contained citric acid in addition to a high concentration of fluorine (89.9%). On the other hand, in Example 2, which contained sodium metaphosphate in addition to a high concentration of fluorine, the residual amount of hinokitiol recovered to 90% or more (92.3%) (based on storage for two weeks at 4°C), maintaining stability. The results are shown in Table 4.

[0064]

[0065] Furthermore, in oral compositions with the compositions shown in Table 2, when sodium monofluorophosphate was replaced with sodium fluoride, stannous fluoride, and silver diamine fluoride to achieve equal fluorine content, the stability of hinokitiol was tested in the same manner as described above, and the same trend as when sodium monofluorophosphate was used was observed.

[0066] 2. Toothpastes with the compositions shown in Tables 5-1, 5-2, and 6 were prepared. The stability of hinokitiol in these oral compositions was tested using the same method as in "1. Hinokitiol Stability Evaluation Test," and a similar trend was observed.

[0067]

[0068]

[0069]

[0070] While the present disclosure has been described above with reference to embodiments, the present disclosure is not limited to the embodiments described above. Various modifications to the structure and details of the present disclosure may be made that will be understood by those skilled in the art within the scope of the present disclosure.

[0071] The patents, patent applications, and documents cited herein are incorporated herein by reference in the same manner as their contents are specifically described herein.

[0072] <Notes> Some or all of the above embodiments and examples may be described as follows, but are not limited to the following. <Oral Compositions of the Disclosure> (Note 1) An oral composition comprising a fluorine compound, hinokitiol, and a metaphosphate, wherein the fluorine content is 1000 ppm or more. (Note 2) The oral composition according to Note 1, wherein the fluorine compound is at least one selected from the group consisting of alkali metal fluorides, fluorophosphate, and salts of fluorophosphate. (Note 3) The oral composition according to Note 1 or 2, wherein the fluorine compound is at least one selected from the group consisting of sodium fluoride, stannous fluoride, silver diamine fluoride, monofluorophosphate, and sodium monofluorophosphate. (Note 4) The oral composition according to any one of Notes 1 to 3, wherein the fluorine compound is sodium monofluorophosphate. (Note 5) The oral composition according to any one of Notes 1 to 4, wherein the fluorine content is 1500 ppm or less. (Note 6) The oral composition according to any one of Notes 1 to 5, wherein the metaphosphate is sodium metaphosphate. (Note 7) The oral composition according to any one of Notes 1 to 6, which is a liquid toothpaste, a tooth paste, or a mouthwash. <Method for producing the oral composition of the present disclosure> (Note 8) The method for producing an oral composition, comprising the step of mixing a fluorine compound, hinokitiol, and a metaphosphate, wherein the fluorine content in the oral composition is 1000 ppm or more. <Method for stabilizing hinokitiol according to the present disclosure> (Note 9) The method for stabilizing hinokitiol in an oral composition, comprising the step of mixing a fluorine compound, hinokitiol, and a metaphosphate, wherein the fluorine content in the oral composition is 1000 ppm or more.

[0073] According to this disclosure, it is possible to provide an oral composition that contains a high concentration of fluorine and hinokitiol while achieving hinokitiol stabilization. The oral composition can exhibit a bactericidal effect due to hinokitiol and a caries prevention effect due to a higher concentration of fluorine than conventional compositions, and the problem of hinokitiol instability is solved by the metaphosphate.

Claims

1. An oral composition comprising a fluorine compound, hinokitiol, and a metaphosphate, wherein the fluorine content is 1000 ppm or more.

2. The oral composition according to claim 1, wherein the fluorine compound is at least one selected from the group consisting of alkali metal fluorides, fluorophosphates, and salts of fluorophosphates.

3. The oral composition according to claim 1 or 2, wherein the fluorine compound is at least one selected from the group consisting of sodium fluoride, stannous fluoride, silver diamine fluoride, monofluorophosphate, and sodium monofluorophosphate.

4. The oral composition according to any one of claims 1 to 3, wherein the fluorine compound is sodium monofluorophosphate.

5. The oral composition according to any one of claims 1 to 4, wherein the fluorine content is 1500 ppm or less.

6. The oral composition according to any one of claims 1 to 5, wherein the metaphosphate is sodium metaphosphate.

7. An oral composition according to any one of claims 1 to 6, which is a liquid toothpaste, a paste toothpaste, or a mouthwash.

8. A method for producing an oral composition, comprising the step of mixing a fluorine compound, hinokitiol, and a metaphosphate, wherein the fluorine content in the oral composition is 1000 ppm or more.

9. A method for stabilizing hinokitiol in an oral composition, comprising the step of mixing a fluorine compound, hinokitiol, and a metaphosphate, wherein the fluorine content in the oral composition is 1000 ppm or more.

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