Oral components

Abstract

The object of this disclosure is to provide an oral composition containing pyridoxines and fluorine compounds, in which the pyridoxines are stabilized. [Solution] An oral composition containing (A) pyridoxines, (B) fluorine compounds, and (C) hinokitiol has stabilized pyridoxines.

Description

Technical Field

[0001] The present disclosure relates to an oral composition in which pyridoxines are stabilized.

Background Art

[0002] Pyridoxines are components known to have a cell-activating effect and are formulated in various oral compositions for the purpose of inactivating the gums, enhancing tissue repair ability, and preventing gingivitis (Patent Documents 1 and 2).

[0003] Fluorine compounds are formulated in various oral compositions for the purpose of supplying fluoride ions to the tooth surface, imparting resistance to acids produced by cariogenic bacteria to the teeth, and remineralizing initial caries (Patent Documents 3 and 4).

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Summary of the Invention

Problems to be Solved by the Invention

[0005] Since pyridoxines are unstable to light, there is a problem in their stable formulation in oral compositions. Furthermore, as a result of the inventors' investigation, when a fluorine compound is formulated in an oral composition, a problem arises in that pyridoxines become even more unstable.

[0006] Therefore, the object of this disclosure is to provide an oral composition containing pyridoxines and fluorine compounds, in which the pyridoxines are stabilized. [Means for solving the problem]

[0007] The inventors of the present invention conducted diligent research to solve the aforementioned problems and found that pyridoxines are stabilized by incorporating hinokitiol into an oral composition containing pyridoxines and fluorine compounds. This disclosure was completed by further research based on this finding.

[0008] In other words, this disclosure provides oral compositions in the following embodiments. Item 1. An oral composition containing (A) pyridoxines, (B) fluorine compounds, and (C) hinokitiol. Item 2. The oral composition according to Item 1, wherein the content of component (C) per 1 part by weight of component (A) is 0.1 parts by weight or more. Item 3. The oral composition according to item 1 or 2, wherein the ratio of component (B) to component (A) is 1 part by weight or more, in terms of the amount of fluorine atoms constituting component (B) per 1 part by weight of component (A). Item 4. The oral composition according to any one of items 1 to 3, wherein the component (B) is selected from the group consisting of alkali metal fluorides, fluorophosphates, and salts of fluorophosphates. Item 5. An oral composition according to any one of items 1 to 4, wherein the content of component (C) is 0.005 to 0.2% by weight. Item 6. An oral composition according to any one of items 1 to 5, wherein the content of component (B) is 1000 to 3000 ppm in terms of the amount of fluorine atoms constituting component (B). Item 7. An oral composition according to any one of items 1 to 6, which is a toothpaste. [Effects of the Invention]

[0009] According to this disclosure, an oral composition is provided which contains pyridoxines and fluorine compounds, in which the pyridoxines are stabilized. [Modes for carrying out the invention]

[0010] The oral composition of this disclosure is characterized by containing (A) pyridoxines (hereinafter also referred to as "component (A)"), (B) fluorine compounds (hereinafter also referred to as "component (B)"), and (C) hinokitiol (hereinafter also referred to as "component (C)"). The oral composition of this disclosure will be described in detail below. In this disclosure, the numerical range "X~Y" refers to a range of X or more and Y or less.

[0011] (A) Pyridoxines The oral compositions of this disclosure contain pyridoxines as component (A). Pyridoxines become even more unstable than their inherent instability when incorporated into oral compositions together with fluorine compounds, but the oral compositions of this disclosure contain pyridoxines together with fluorine compounds, while the pyridoxines are stabilized.

[0012] In this disclosure, pyridoxines are pyridoxine, pyridoxal, pyridoxamine, and salts thereof.

[0013] When pyridoxines are in the form of salts, there are no particular restrictions on the type of salt, as long as it is pharmaceutically acceptable. Examples include inorganic salts, and more specifically, hydrochloride salts, sulfate salts, nitrates, hydrobromide salts, phosphate salts, etc.

[0014] These pyridoxines may be used individually or in combination of two or more.

[0015] Among these pyridoxines, pyridoxine or its salts are preferred, more preferably pyridoxine salts, and even more preferably pyridoxine hydrochloride salts.

[0016] In the oral composition of the present disclosure, the content of the component (A) is not particularly limited and may be appropriately set according to the degree to which the effects of pyridoxines are required, etc. For example, it may be 0.005 to 2% by weight, 0.005 to 1% by weight, 0.005 to 0.5% by weight, or 0.005 to 0.1% by weight, preferably 0.01 to 0.08% by weight, more preferably 0.015 to 0.05% by weight, 0.015 to 0.04% by weight, or 0.015 to 0.3% by weight.

[0017] (B) Fluorine compounds The oral composition of the present disclosure contains a fluorine compound as the component (B). When the fluorine compound is blended with pyridoxines in the oral composition, the action of fluoride ions further destabilizes pyridoxines compared to their original instability. However, the oral composition of the present disclosure contains the fluorine compound together with pyridoxines, but the pyridoxines are stabilized.

[0018] In the present disclosure, the fluorine compound is a known component that has the action of imparting resistance to acids produced by cariogenic bacteria to teeth and remineralizing incipient caries by supplying fluoride ions to the tooth surface. The fluorine compound used in the present disclosure is not particularly limited as long as it is applicable in the oral cavity. For example, it includes fluorides of alkali metals, fluorophosphoric acid, salts of fluorophosphoric acid, stannous fluoride, and silver diamine fluoride, etc.

[0019] The fluorides of alkali metals are not particularly limited as long as they are applicable in the oral cavity. For example, they include sodium fluoride and potassium fluoride, etc. These fluorides of alkali metals may be used alone or in combination of two or more.

[0020] The fluorophosphoric acid is not particularly limited as long as it is applicable in the oral cavity. For example, it includes monofluorophosphoric acid and difluorophosphoric acid, etc. These fluorophosphoric acids may be used alone or in combination of two or more.

[0021] The salts of fluorophosphoric acid are not particularly limited as long as they are applicable in the oral cavity. For example, alkali metal salts of the fluorophosphoric acid, specifically, sodium salts and potassium salts of the fluorophosphoric acid, etc. may be mentioned. These salts of fluorophosphoric acid may be used alone or in combination of two or more.

[0022] The oral composition of the present disclosure may use, as the component (B), one selected from alkali metal fluoride, fluorophosphoric acid, salts of fluorophosphoric acid, stannous fluoride, and silver diamine fluoride, or may use a combination of two or more.

[0023] Among these component (B), preferably, it is selected from the group consisting of alkali metal fluoride, fluorophosphoric acid, and salts of fluorophosphoric acid, more preferably fluorophosphoric acid and salts of fluorophosphoric acid, still more preferably monofluorophosphoric acid and salts of monofluorophosphoric acid, even more preferably salts of monofluorophosphoric acid, particularly preferably sodium monofluorophosphate.

[0024] The content of component (B) in the oral composition of this disclosure is not particularly limited, but the amount of fluorine atoms constituting component (B) per 1 part by weight of component (A) is, for example, 1 part by weight or more. From the viewpoint of obtaining an even better stabilization effect of component (A), the amount of fluorine atoms constituting component (B) per 1 part by weight of component (A) is preferably 1 to 30 parts by weight, more preferably 1 to 20 parts by weight, even more preferably 1 to 15 parts by weight, even more preferably 1 to 10 parts by weight, and particularly preferably 1 to 8 parts by weight. Furthermore, since the oral composition of this disclosure has an excellent stabilization effect of component (A), an effective stabilization effect of component (A) can be obtained even when the ratio of component (B) to component (A) is relatively high. From this viewpoint, preferred examples of the amount of fluorine atoms constituting component (B) per 1 part by weight of component (A) include 3.5 to 30 parts by weight, 4.5 to 30 parts by weight, 5.5 to 30 parts by weight, 6.5 to 30 parts by weight, or 7 to 30 parts by weight.

[0025] Furthermore, the specific content of component (B) in the oral composition of this disclosure is determined by the content of component (A) and the amount of fluorine atoms constituting component (B) per 1 part by weight of component (A). However, from the viewpoint of obtaining an even better stabilizing effect of component (A), the amount of fluorine atoms constituting component (B) is preferably 1000 to 3000 ppm. In addition, since the oral composition of this disclosure has an excellent stabilizing effect of component (A), the stabilizing effect of component (A) can be effectively obtained even when the amount of component (B) is relatively large. From this viewpoint, preferred examples of the specific content of component (B) include the amount of fluorine atoms constituting component (B) being 1200 to 3000 ppm, 1300 to 3000 ppm, 1400 to 3000 ppm, 1400 to 1700 ppm, or 1400 to 1500 ppm.

[0026] (C) Hinokitiol The oral composition of this disclosure contains hinokitiol as component (C). Hinokitiol stabilizes pyridoxines when incorporated into an oral composition containing pyridoxines together with a fluorine compound.

[0027] The content of component (C) in the oral composition of this disclosure is not particularly limited and may be set appropriately depending on the desired degree of stabilization effect of component (A). For example, the content per 1 part by weight of component (A) is 0.1 parts by weight or more. From the viewpoint of obtaining an even better stabilization effect of component (A), preferred content of component (C) per 1 part by weight of component (A) is 0.2 parts by weight or more, or 0.4 parts by weight or more, more preferably 0.8 parts by weight or more, 0.9 parts by weight or more, or 1.4 parts by weight or more, and even more preferably 1.6 parts by weight or more, or 1.8 parts by weight or more. The upper limit of the content of component (C) per 1 part by weight of component (A) is not particularly limited, but for example, it is 10 parts by weight or less, specifically 0.1 to 10 parts by weight, 0.1 to 8 parts by weight, 0.1 to 6 parts by weight, 0.1 to 4 parts by weight, 0.1 to 2.5 parts by weight, 0.1 to 2 parts by weight, or 0.1 to 1.5 parts by weight.

[0028] The specific content of component (C) in the oral composition of this disclosure is determined by the content of component (A) and the ratio of the content of component (A) and component (C), but examples include 0.005 to 0.2% by weight, and from the viewpoint of obtaining an even better stabilizing effect of component (A), preferably 0.01 to 0.2% by weight, more preferably 0.018 to 0.2% by weight, 0.018 to 0.1% by weight, or 0.018 to 0.05% by weight.

[0029] Other ingredients In addition to the components described above, the oral composition of the present invention may contain, or may not contain, one or more components commonly used in the art, as long as they do not impair the effects of the present invention. Examples of such optional components include water, preservatives, bactericides, antibacterial agents, antioxidants, anti-inflammatory agents, abrasives, thickeners, glucosyltransferase (GTase) inhibitors, plaque inhibitors, hypersensitivity inhibitors, tartar preventives, local anesthetics, blood circulation promoters, humectants, sweeteners, dyes / pigments, deodorants, surfactants, monohydric lower alcohols, buffers, pH adjusters, and the like.

[0030] Examples of agents that suppress hypersensitivity include aluminum lactate and potassium nitrate.

[0031] Examples of wetting agents include polyhydric alcohols (dihydric alcohols such as 1,3-butylene glycol, ethylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, polyethylene glycol, etc.; glycerin, etc.), sugar alcohols (sorbitol, mannitol, xylitol, erythritol, etc.), and phosphocholine group-containing polymers.

[0032] Examples of monohydric lower alcohols include monohydric alcohols with 2 to 5 carbon atoms, specifically ethanol, propanol, isopropanol, and butanol.

[0033] Examples of surfactants include anionic surfactants, nonionic surfactants, and amphoteric surfactants. Examples of nonionic surfactants include polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ethers, glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, sucrose fatty acid esters, polyalkylene glycol fatty acid esters, polyoxyethylene sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters. Examples of amphoteric surfactants include acetate betaine-type surfactants such as alkyl betaine, alkyldimethylaminoacetic acid betaine, and fatty acid amidopropyl betaine; betaine-type surfactants such as alkylimidazolinium betaine; and imidazoline-type surfactants such as N-fatty acid acyl-N-carboxymethyl-N-hydroxyethylethylenediamine salt. The HLB of nonionic surfactants is not particularly limited, but for example, it can be 11.0 to 16.0, preferably 12.0 to 15.5, and more preferably 13.0 to 15.0.

[0034] The HLB (Hydrophile-Lypophile Balance) value is a value that indicates the affinity of a nonionic surfactant for water and oil. In this disclosure, the HLB value of the nonionic surfactant is a value obtained by a measurement method that conforms to the actual measurement of HLB values ​​by emulsification method described on pages 854-855 of "Handbook - Cosmetics and Pharmaceutical Raw Materials - Revised Edition," Nikko Chemicals Co., Ltd., revised edition published February 1, 1977. Specifically, the nonionic surfactant to be measured for HLB value is combined with polyoxyethylene sorbitan monostearate (NIKKOL TS-10, HLB 14.9) as a standard substance, and the total amount of these two emulsifiers is kept constant, while only the ratio is changed to emulsify liquid paraffin (HLB 10.1), which is the substance to be emulsified. After standing for 24 hours, the optimal ratio of surfactant at which stability is determined from the amount of creaming, turbidity, and water separation of the lower layer, and the HLB value x of the surfactant is calculated using the following formula (1). y=(x×Amount used (mass%)+z×Amount used (mass%)) / 100...Formula (1) In equation (1) above, x represents the HLB value of the nonionic surfactant (the substance being measured), y represents the HLB value of the liquid paraffin, and z represents the HLB value of polyoxyethylene sorbitan monostearate (the standard substance). The HLB value of the liquid paraffin can be determined in a similar manner by combining sorbitan monostearate (NIKKOL SS-10, HLB 4.7) and polyoxyethylene sorbitan monostearate (NIKKOL TS-10, HLB 14.9).

[0035] A preferred example of an oral composition of the present disclosure includes, as other components, water; a surfactant (preferably a nonionic surfactant, more preferably polyoxyethylene hydrogenated castor oil); aluminum lactate; a polyhydric alcohol (preferably glycerin); and one or more monohydric lower alcohols (preferably ethanol).

[0036] The oral compositions of the present disclosure typically contain water. The water content in the oral compositions of the present disclosure is not particularly limited, but examples include 20 to 90% by weight, preferably 25 to 80% by weight, 30 to 70% by weight, or 30 to 60% by weight.

[0037] If the oral composition of this disclosure contains aluminum lactate, the content of the component may be, for example, 0.1 to 5% by weight, preferably 0.3 to 3% by weight, and more preferably 0.4 to 1% by weight. If the oral composition of this disclosure contains polyhydric alcohol, the content of the component may be, for example, 1 to 75% by weight, preferably 10 to 55% by weight, and more preferably 20 to 40% by weight. In the oral composition of this disclosure, the content of the surfactant may be, for example, 0.1 to 10% by weight, 0.5 to 7% by weight, and more preferably 0.8 to 5.5% by weight, of which the content of the nonionic surfactant may be, for example, 0.1 to 10% by weight, 0.3 to 5% by weight, more preferably 0.5 to 4% by weight, and more preferably 0.8 to 3.5% by weight or 0.8 to 3.2% by weight. If the oral composition of this disclosure contains a monohydric lower alcohol, the content of the component may be, for example, 0.1 to 15% by weight, preferably 1 to 13% by weight, and more preferably 5 to 11% by weight.

[0038] In preferred examples of oral compositions of this disclosure, other components do not include phosphocholine group-containing polymers.

[0039] pH The pH of the oral composition of this disclosure can be selected without particular limitation from the pH ranges generally applied to oral compositions, but examples include 4 to 7, preferably 4 to 6, more preferably 4 to 5, and even more preferably 4.3 to 4.7. In this disclosure, the pH of the oral composition is a value measured under a temperature condition of 25°C. To adjust the pH to the range described above, buffering agents, pH adjusting agents, etc., may be used.

[0040] Formulation form / dosage type The dosage form of the oral composition of this disclosure is not particularly limited, as long as it is applicable in the oral cavity, but examples include liquid or semi-solid forms (gel or paste).

[0041] The formulation of the oral composition disclosed herein 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 toothpaste (liquid toothpaste, paste toothpaste, etc.), mouthwash (sometimes called mouth rinse, mouthwash, dental rinse, etc.), oral freshener (mouth spray, etc.), and oral ointment. Among these, toothpaste is preferred.

[0042] Manufacturing method The oral compositions of this disclosure can be manufactured according to known formulation methods corresponding to their formulation form. [Examples]

[0043] The present disclosure will be explained in more detail below with reference to examples, but the present disclosure is not limited to these examples.

[0044] Test example Oral compositions (toothpastes) were prepared by mixing the ingredients shown in Table 1 in the indicated amounts. The HLB of POE hydrogenated castor oil (60EO) was 14.0. The prepared oral compositions were filled into colorless, transparent containers, sealed, and irradiated with a white fluorescent lamp at 25°C for one week using an LT-120A (Nagano Science Co., Ltd.). The pyridoxine hydrochloride content was quantified by the method described below, and the pyridoxine hydrochloride reduction rate (%) was derived based on formula (I). The results are shown in Table 1.

[0045] [Quantitative method] Equipment used: High-performance liquid chromatograph LCMS-2020 (Shimadzu Corporation) Detector: UV absorbance spectrophotometer - Measurement wavelength: 292 nm Column L-column2 ODS, 15cm in length Column temperature: 40°C Mobile phase: 1-Sodium octanesulfonate solution / acetonitrile mixture Flow rate. The retention time for pyridoxine hydrochloride was set to approximately 7.4 minutes.

[0046]

number

[0047] [Table 1]

[0048] As shown in Table 1, the oral composition containing component (A) showed poor stability of component (A) (Comparative Example 1), and the stability of component (A) further deteriorated when component (B) was added (Comparative Example 2). In contrast, when component (C) was further added to the oral composition containing components (A) and (B), the stability of component (A) improved significantly (Examples 1-5). In particular, when the amount of component (C) was increased to the amounts shown in Examples 2-5, the stability of component (A) improved even more significantly.

[0049] Prescription examples Oral compositions (toothpastes) were prepared according to the formulations shown in Tables 2 and 3. All oral compositions exhibited excellent stability of pyridoxine hydrochloride.

[0050] [Table 2]

[0051] [Table 3]

Claims

1. An oral composition containing (A) pyridoxines, (B) fluorine compounds, and (C) hinokitiol.

2. The oral composition according to claim 1, wherein the content of component (C) per 1 part by weight of component (A) is 0.1 parts by weight or more.

3. The oral composition according to claim 1 or 2, wherein the ratio of component (B) to component (A) is 1 part by weight or more, in terms of the amount of fluorine atoms constituting component (B) per 1 part by weight of component (A).

4. The oral composition according to claim 1 or 2, wherein the component (B) is selected from the group consisting of alkali metal fluorides, fluorophosphates, and salts of fluorophosphates.

5. The oral composition according to claim 1 or 2, wherein the content of component (C) is 0.005 to 0.2% by weight.

6. The oral composition according to claim 1 or 2, wherein the content of component (B) is 1,000 to 3,000 ppm in terms of the amount of fluorine atoms constituting component (B).

7. An oral composition according to claim 1 or 2, which is a toothpaste.

Images