Oral components

Abstract

The object of this disclosure is to provide an oral composition in which pyridoxines are stabilized. [Solution] An oral composition containing (A) pyridoxines, (B) nonionic surfactants, and (C) glycyrrhetinic acids, wherein the content of component (C) is 2 parts by weight or more per 1 part by weight of component (A), wherein the pyridoxines are stabilized.

Description

Technical Field

[0006] ,

[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).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] Since pyridoxines are unstable to light, there is a problem in the stable formulation in oral compositions. Therefore, an object of the present disclosure is to provide an oral composition in which pyridoxines are stabilized.

Means for Solving the Problems

[0005] The inventor of the present invention conducted intensive studies to solve the above problems and found that when glycyrrhetinic acids are formulated in an oral composition containing pyridoxines and a nonionic surfactant at a ratio of 2 parts by weight or more per 1 part by weight of pyridoxines, the pyridoxines are stabilized. The present disclosure was completed by further studies based on this finding.

[0006] That is, the present disclosure provides an oral composition in the following aspects. Item 1. An oral composition comprising (A) pyridoxines, (B) nonionic surfactants, and (C) glycyrrhetinic acids, wherein the content of component (C) is 2 parts by weight or more per 1 part by weight of component (A). Item 2. The oral composition according to Item 1, wherein the content of component (B) per 1 part by weight of component (C) is 1 to 200 parts by weight. Item 3. The oral composition according to item 1 or 2, wherein the content of component (C) is 0.01 to 0.5% by weight. Item 4. An oral composition according to any one of items 1 to 3, wherein the content of component (B) is 0.5 to 5% by weight. Item 5. An oral composition according to any one of items 1 to 4, which is a toothpaste. [Effects of the Invention]

[0007] According to this disclosure, oral compositions containing stabilized pyridoxines are provided. [Modes for carrying out the invention]

[0008] The oral composition of this disclosure is characterized by containing (A) pyridoxines (hereinafter also referred to as "component (A)"), (B) nonionic surfactants (hereinafter also referred to as "component (B)"), and (C) glycyrrhetinic acids (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.

[0009] (A) Pyridoxines The oral compositions of this disclosure contain pyridoxines as component (A). In the oral compositions of this disclosure, the pyridoxines are stabilized by being co-compounded with glycyrrhetinic acid.

[0010] In this disclosure, pyridoxines are pyridoxine, pyridoxal, pyridoxamine, and salts thereof.

[0011] 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.

[0012] These pyridoxines may be used individually or in combination of two or more.

[0013] Among these pyridoxines, pyridoxine or its salts are preferred, more preferably pyridoxine salts, and even more preferably pyridoxine hydrochloride salts.

[0014] In the oral compositions of this disclosure, the content of component (A) is not particularly limited and may be set appropriately depending on the desired degree of pyridoxine-like effects, but examples include 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 0.03% by weight.

[0015] (B) Nonionic surfactants The oral composition of this disclosure contains a nonionic surfactant as component (B). In the oral composition of this disclosure, the nonionic surfactant is thought to assist in the stabilization of pyridoxines by glycyrrhetinic acid.

[0016] The type of nonionic surfactant is not particularly limited, but examples include polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene alkyl ether, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, sorbitan fatty acid ester, polyoxyethylene alkyl ether, polyethylene glycol fatty acid ester, and the like. Among these, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, and polyoxyethylene polyoxypropylene alkyl ether are preferred, and polyoxyethylene hydrogenated castor oil is preferred.

[0017] The HLB of the nonionic surfactant is not particularly limited, but examples include 11.0 to 16.0, and from the viewpoint of obtaining an even better stabilizing effect of component (A), it is preferably 12.0 to 15.5, and more preferably 13.0 to 15.0.

[0018] 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 × usage amount (mass%) + z × usage amount (mass%)) / 100 ··· Equation (1) In the above Equation (1), x represents the HLB value of the nonionic surfactant (measurement target), y represents the HLB value of liquid paraffin, and z represents the HLB value of polyoxyethylene sorbitan monostearate (standard substance). Note that the HLB value of the liquid paraffin can be obtained by the same method using a combination of sorbitan monostearate (NIKKOL SS-10, HLB 4.7) and polyoxyethylene sorbitan monostearate (NIKKOL TS-10, HLB 14.9).

[0019] Specific examples of nonionic surfactants with an HLB value of 11.0 to 16.0 include POE hydrogenated castor oils such as POE hydrogenated castor oil 30, POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, and POE hydrogenated castor oil 60; POE sorbitan fatty acid esters such as POE(20) sorbitan tristearate, POE(20) sorbitan trioleate, POE(20) sorbitan monooleate, and POE(20) sorbitan monoisostearate; POEPOE alkyl ethers such as POE(20)POP(8) cetyl ether, POE(30)POP(6) decyltetradecyl ether, and POE(20)POP(6) decyltetradecyl ether; POE alkyl ethers such as POE(9) lauryl ether, POE(10) cetyl 3 ether, and POE(10) oleyl ether; polyglycerol fatty acid esters such as hexaglyceryl monolaurate and decaglyceryl monomyristate; POE glycerol fatty acid esters such as POE(15) glyceryl monooleate; and POE sorbitol fatty acid esters such as POE(60) sorbitol tetrastearate, POE(40) sorbitol tetraoleate, and POE(60) sorbitol tetraoleate. Here, "POE" is an abbreviation for polyoxyethylene, "POP" is an abbreviation for polyoxypropylene, and the numerical value in parentheses shown after POE or POP is the average number of added moles.

[0020] In the oral composition of the present disclosure, as the component (B), one kind may be selected from the above nonionic surfactants and used alone, or two or more kinds may be used in combination.

[0021] Among the component (B), from the viewpoint of obtaining a more excellent stabilizing effect of the component (A), preferably, POE hydrogenated castor oil, more preferably, POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, and even more preferably, POE hydrogenated castor oil 60 can be mentioned.

[0022] In the oral composition of the present disclosure, the content of the component (B) is not particularly limited and may be appropriately set according to the degree required for the stabilizing effect of the component (A). For example, 0.1 to 10% by weight can be mentioned. From the viewpoint of obtaining a more excellent stabilizing effect of the component (A), preferably 0.3 to 10% by weight, more preferably 0.5 to 10% by weight, even more preferably 0.8 to 10% by weight, 1.8 to 10% by weight, or 2.8 to 10% by weight can be mentioned. Further, since the component (C) formulated in a specific ratio in the oral composition of the present disclosure contributes to the stabilizing effect of the component (A), even if the amount of the nonionic surfactant is small, the stabilizing effect of the component (A) can be effectively obtained. From such a viewpoint, preferable examples of the content of the component (B) in the oral composition of the present disclosure include 0.1 to 7% by weight, more preferably 0.1 to 5% by weight, even more preferably 0.1 to 3.2% by weight, 0.1 to 2.2% by weight, or 0.1 to 1.2% by weight.

[0023] In the oral composition of this disclosure, there are no particular limitations on the content of component (B) per 1 part by weight of component (C). However, from the viewpoint of obtaining an even better stabilizing effect of component (A), the content of component (B) per 1 part by weight of component (C) can be 1 to 200 parts by weight, preferably 3 to 200 parts by weight, more preferably 5 to 200 parts by weight, 9 to 200 parts by weight, 18 to 200 parts by weight, 28 to 200 parts by weight, 38 to 200 parts by weight, 48 to 200 parts by weight, or 58 to 200 parts by weight. Furthermore, in the oral composition of this disclosure, since component (C), which is blended in a specific ratio, contributes to the stabilizing effect of component (A), an effective stabilizing effect of component (A) can be obtained even if the ratio of nonionic surfactant to component (C) is low. From this viewpoint, preferred examples of the content of component (B) per 1 part by weight of component (C) in the oral composition of the present disclosure include 1 to 100 parts by weight, 1 to 75 parts by weight, 1 to 65 parts by weight, 1 to 55 parts by weight, 1 to 45 parts by weight, 1 to 35 parts by weight, or 1 to 25 parts by weight.

[0024] (C) Glycyrrhetinic acid derivatives The oral composition of this disclosure contains glycyrrhetinic acid as component (C). Glycyrrhetinic acid stabilizes pyridoxines when added in a specific ratio to pyridoxines in an oral composition containing pyridoxines and a nonionic surfactant.

[0025] In this disclosure, glycyrrhetinic acids are selected from the group consisting of glycyrrhetinic acid, its derivatives, and salts thereof.

[0026] Examples of glycyrrhetinic acid include α-glycyrrhetinic acid and β-glycyrrhetinic acid. These glycyrrhetins may be used individually or in combination of two or more types.

[0027] While there are no particular restrictions on the derivatives of glycyrrhetinic acid, provided they are pharmaceutically acceptable, specific examples include pyridoxine glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glycyrrhetinate, and monoglucuronide glycyrrhetinate. These derivatives of glycyrrhetinic acid may be used individually or in combination of two or more.

[0028] The salts of glycyrrhetinic acid and / or its derivatives are not particularly limited as long as they are pharmaceutically acceptable, but specific examples include alkali metal salts such as sodium salts and potassium salts; and ammonium salts. These salts may be used individually or in combination of two or more.

[0029] The oral compositions of this disclosure may use one selected from glycyrrhetinic acid, a salt of glycyrrhetinic acid, a derivative of glycyrrhetinic acid, and a salt of a derivative of glycyrrhetinic acid as component (C), or two or more may be used in combination.

[0030] Among these (C) components, glycyrrhetinic acid is preferred, and β-glycyrrhizic acid is more preferred.

[0031] In the oral composition of this disclosure, component (C) is included in an amount of 2 parts by weight or more per 1 part by weight of component (A). From the viewpoint of obtaining an even better stabilizing effect of component (A), preferred amounts of component (C) per 1 part by weight of component (A) include 2.2 parts by weight or more, 2.4 parts by weight or more, 4 parts by weight or more, 6 parts by weight or more, and more preferably 8 parts by weight or more. The upper limit of the amount of component (C) per 1 part by weight of component (A) is not particularly limited, but for example, it may be 60 parts by weight or less, specifically 2 to 60 parts by weight, 2 to 40 parts by weight, 2 to 20 parts by weight, 2 to 15 parts by weight, 2 to 12 parts by weight, 2 to 8 parts by weight, 2 to 6 parts by weight, 2 to 4 parts by weight, or 2 to 3 parts by weight.

[0032] In the oral composition of this disclosure, the specific content of component (C) is determined by the content of component (A) and the ratio of the content of component (A) and component (C), but examples include 0.03% by weight or more, preferably 0.04% by weight or more, 0.06% by weight or more, 0.08% by weight or more, more preferably 0.15% by weight or more, or 0.18% by weight or more. In the oral composition of this disclosure, the specific content of component (C) is not particularly limited in terms of its upper limit, but examples include 0.3% by weight or less, specifically 0.03 to 0.3% by weight, 0.03 to 0.2% by weight, 0.03 to 0.15% by weight, 0.03 to 0.1% by weight, or 0.03 to 0.08% by weight.

[0033] Other ingredients In addition to the components described above, the oral compositions of this disclosure 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, desensitizers, tartar preventives, tooth strengthening / remineralizing agents, local anesthetics, blood circulation promoters, humectants, sweeteners, dyes / pigments, deodorants, surfactants (other than component (B)), monohydric lower alcohols, buffers, pH adjusters, and the like.

[0034] Examples of antioxidants include rutin, rutin glycosides, tocopherol, and esters of tocopherol with organic acids (e.g., tocopherol acetate, tocopherol nicotinate, etc.).

[0035] Examples of agents that suppress hypersensitivity include aluminum lactate and potassium nitrate.

[0036] Examples of tooth strengthening / remineralizing agents include fluorine compounds, more specifically alkali metal fluorides (sodium fluoride, potassium fluoride, etc.), fluorophosphates (monofluorophosphate, difluorophosphate, etc.), and salts of fluorophosphates (alkali metal salts of the aforementioned fluorophosphates, more specifically sodium salts, potassium salts, etc. of the aforementioned fluorophosphates).

[0037] 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.

[0038] Examples of monohydric lower alcohols include monohydric alcohols with 2 to 5 carbon atoms, specifically ethanol, propanol, isopropanol, and butanol.

[0039] A preferred example of an oral composition of the present disclosure includes, as other components, water; alkali metal fluoride, fluorophosphate, and / or salt of fluorophosphate (preferably a salt of fluorophosphate, more preferably an alkali metal salt of fluorophosphate, even more preferably an alkali metal salt of monomonofluorophosphate, and even more preferably sodium monofluorophosphate); aluminum lactate; polyhydric alcohol (preferably glycerin); and monohydric lower alcohol (preferably ethanol).

[0040] 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, more preferably 30 to 70% by weight, or 30 to 60% by weight.

[0041] If the oral composition of this disclosure contains alkali metal fluorides, fluorophosphates, and / or salts of fluorophosphates, the total content of these components may be, for example, 0.001 to 5% by weight, preferably 0.01 to 3% by weight, more preferably 0.1 to 2% by weight, and even more preferably 0.5 to 1.5% by weight. If the oral composition of this disclosure contains aluminum lactate, the content of this component may be, for example, 0.1 to 5% by weight, preferably 0.3 to 3% by weight, and even more preferably 0.4 to 1% by weight. If the oral composition of this disclosure contains polyhydric alcohols, the content of this component may be, for example, 1 to 75% by weight, preferably 10 to 55% by weight, and even more preferably 20 to 40% by weight. In the oral composition of this disclosure, the total amount of surfactants (other than component (B)) and component (B) may be, for example, 0.1 to 10% by weight, 0.5 to 7% by weight, and even more preferably 0.8 to 5.5% 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.

[0042] In preferred examples of oral compositions of the present disclosure, other components include one or more of the following: rutin, rutin glycosides, tocopherol, esters of tocopherol with organic acids (e.g., tocopherol acetate, tocopherol nicotinate, etc.), and sugar alcohols.

[0043] 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.

[0044] 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).

[0045] 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.

[0046] Manufacturing method The oral compositions of this disclosure can be manufactured according to known formulation methods corresponding to their formulation form. [Examples]

[0047] The present disclosure will be explained in more detail below with reference to examples, but the present disclosure is not limited to these examples.

[0048] Test example Oral compositions (toothpastes) were prepared by mixing the ingredients shown in Tables 1 and 2 in the indicated proportions. 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 Tables 1 and 2.

[0049] [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.

[0050]

number

[0051] [Table 1]

[0052] [Table 2]

[0053] As shown in Table 1, oral compositions containing component (A) and component (C) but not component (B) exhibited poor stability of component (A). The stability of component (A) deteriorated significantly as the ratio of component (C) to component (A) increased (Comparative Examples 1-3). When the content of component (C) per 1 part by weight of component (A) was 2 parts by weight or more (hereinafter also referred to as the "predetermined ratio"), the stability of component (A) deteriorated particularly badly (Comparative Example 3). Furthermore, when component (B) was added to an oral composition containing component (A) and component (C) in a ratio below the predetermined ratio, a tendency toward stabilization of component (A) was observed. However, even when the amount of component (B) was increased, the level of stabilization was not satisfactory (Comparative Examples 4-6).

[0054] On the other hand, as shown in Table 2, when component (B) was added to an oral composition containing component (A) and component (C) in a predetermined ratio, the stability of component (A) was significantly improved (Examples 1-5). For example, as shown in Example 1, which is compared with Comparative Example 5, and Example 2, which is compared with Comparative Example 6, the stability of component (A) was improved simply by adding component (C) in a predetermined ratio. Also, for example, as shown in Comparative Example 5, which is compared with Comparative Example 2, when 1% by weight of component (B) was added to an oral composition containing 0.02% by weight of component (A) and component (C) in a ratio below the predetermined ratio, the reduction rate of component (A) was improved by 5.5%, whereas, as shown in Example 1, which is compared with Comparative Example 3, when 1% by weight of component (B) was added to an oral composition containing 0.02% by weight of component (A) and component (C) in a predetermined ratio, the reduction rate of component (A) was improved by as much as 9.8%. Thus, it was found that the remarkable improvement in the stability of component (A) observed in Examples 1 to 5 is a unique effect resulting from selecting a predetermined ratio for the amount of component (C) included.

[0055] Prescription examples Oral compositions (toothpastes) were prepared according to the formulations shown in Table 3. All oral compositions exhibited excellent stability of pyridoxine hydrochloride.

[0056] [Table 3]

Claims

1. An oral composition comprising (A) pyridoxines, (B) nonionic surfactants, and (C) glycyrrhetinic acids, wherein the content of component (C) is 2 parts by weight or more per 1 part by weight of component (A).

2. The oral composition according to claim 1, wherein the content of component (B) per 1 part by weight of component (C) is 1 to 200 parts by weight.

3. The oral composition according to claim 1 or 2, wherein the content of component (C) is 0.01 to 0.5% by weight.

4. The oral composition according to claim 1 or 2, wherein the content of component (B) is 0.5 to 5% by weight.

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

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