Oral components

Abstract

The object of this disclosure is to provide an oral composition in which glycyrrhetinic acid derivatives are solubilized. [Solution] An oral composition comprising (A) glycyrrhetinic acid, (B) ethanol, (C) nonionic surfactant, (D) pyridoxine, and (E) water, wherein the glycyrrhetinic acid is solubilized.

Description

Technical Field

[0006] , , , , ,

[0001] The present disclosure relates to an oral composition in which glycyrrhetinic acids are solubilized.

Background Art

[0002] Glycyrrhetinic acid, its derivatives, and their salts (glycyrrhetinic acids) are components known to have anti-inflammatory effects and are formulated in various oral compositions for the purpose of preventing or improving periodontitis or periodontal disease, etc. (Patent Documents 1, 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] Glycyrrhetinic acids are lipophilic and have low solubility in water. Therefore, solubilizing glycyrrhetinic acids in an oral composition is important in ensuring the homogeneity between batches and guaranteeing the consistent quality of the product in the preparation of the oral composition.

[0005] Therefore, an object of the present disclosure is to provide an oral composition in which glycyrrhetinic acids are solubilized.

Means for Solving the Problems

[0006] The inventors of the present invention conducted diligent studies to solve the aforementioned problems and discovered that glycyrrhetinic acid derivatives can be solubilized by adding pyridoxines to an oral composition containing glycyrrhetinic acid derivatives, ethanol, and a nonionic surfactant in water. This disclosure was completed by further studies based on this finding.

[0007] In other words, this disclosure provides oral compositions in the following embodiments. Item 1. An oral composition comprising (A) glycyrrhetinic acid, (B) ethanol, (C) nonionic surfactant, (D) pyridoxine, and (E) water. Item 2. The oral composition according to Item 1, wherein the content of component (B) per 1 part by weight of component (A) is 3 to 90 parts by weight. Item 3. The oral composition according to item 1 or 2, wherein the content of component (C) per 1 part by weight of component (A) is 1 to 200 parts by weight. Item 4. The oral composition according to any one of items 1 to 3, wherein the content of component (D) per single portion of component (A) is 0.05 parts by weight or more. Item 5. An oral composition according to any one of items 1 to 4, which is a toothpaste. [Effects of the Invention]

[0008] According to this disclosure, oral compositions in which glycyrrhetinic acid derivatives are solubilized are provided. [Modes for carrying out the invention]

[0009] The oral composition of this disclosure is characterized by comprising (A) glycyrrhetinic acid (hereinafter also referred to as "component (A)"), (B) ethanol (hereinafter also referred to as "component (B)"), (C) nonionic surfactant (hereinafter also referred to as "component (C)"), (D) pyridoxine (hereinafter also referred to as "component (D)"), and (E) water (hereinafter also referred to as "component (E)"). 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.

[0010] (A) Glycyrrhetinic acid derivatives The oral composition of this disclosure contains glycyrrhetinic acid as component (A). Although glycyrrhetinic acid has low solubility in water, in the oral composition of this disclosure, glycyrrhetinic acid is solubilized by the co-combination of pyridoxines with ethanol and a nonionic surfactant.

[0011] In this disclosure, glycyrrhetinic acids are selected from the group consisting of glycyrrhetinic acid, its derivatives, and salts thereof.

[0012] 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.

[0013] 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.

[0014] 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.

[0015] 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 (A), or two or more may be used in combination.

[0016] Among these components (A), glycyrrhetinic acid is preferred, and β-glycyrrhizic acid is more preferred.

[0017] The content of component (A) in the oral composition of this disclosure is not particularly limited and may be set appropriately according to the desired degree of anti-inflammatory effect, etc., but for example, the total amount of component (A) may be 0.01% by weight or more, 0.03% by weight or more, 0.045% by weight or more, 0.8% by weight or more, 1.4% by weight or more, or 1.8% by weight or more. Inherently, the insolubility problem of component (A) can become significant when the content is 0.045% by weight or more, but in the oral composition of this disclosure, component (A) can be effectively solubilized even at such a content. From this viewpoint, preferred examples of the content of component (A) in the oral composition of this disclosure include 0.045% by weight or more, 0.8% by weight or more, 1.4% by weight or more, or 1.8% by weight or more. Furthermore, the content of component (A) in the oral composition of this disclosure is not particularly limited in terms of its upper limit, but from the viewpoint of obtaining an even better solubilizing effect, for example, it may be 0.2% by weight or less, specifically 0.01 to 0.2% by weight, 0.01 to 0.15% by weight, or 0.01 to 0.06% by weight.

[0018] (B) Ethanol The oral composition of the present disclosure contains ethanol as component (B). In the oral composition of the present disclosure, ethanol solubilizes glycyrrhetinic acids by being co-formulated with a nonionic surfactant and pyridoxines.

[0019] The content of component (B) in the oral composition of the present disclosure is not particularly limited and may be appropriately set according to the degree of solubilization effect required. For example, it may be 0.1 to 1.5% by weight. From the viewpoint of obtaining a more excellent solubilization effect, it is preferably 0.3 to 1.5% by weight, more preferably 0.5 to 1.5% by weight, and still more preferably 0.6 to 1.5% by weight. Further, since the oral composition of the present disclosure has an excellent solubilization effect on component (A), an effective solubilization effect can be obtained even with a small amount of ethanol. From such a viewpoint, suitable examples of the content of component (B) in the oral composition of the present disclosure include 0.1 to 1% by weight, more preferably 0.1 to 0.8% by weight, and still more preferably 0.1 to 0.6% by weight.

[0020] In the oral composition of the present disclosure, the ratio of the component (A) to the component (B) is not particularly limited and is determined according to the respective contents of the aforementioned component (A) and component (B). However, from the viewpoint of obtaining a more excellent solubilization effect, examples of the content of the component (B) per 1 part by weight of the component (A) include, for example, 3 to 90 parts by weight, preferably 7 to 90 parts by weight, more preferably 10 to 90 parts by weight, and still more preferably 13 to 90 parts by weight. Further, since the oral composition of the present disclosure is excellent in the solubilization effect of the component (A), even when the ratio of ethanol to the component (A) is low, the solubilization effect can be effectively obtained. From such a viewpoint, preferred examples of the content of the component (B) per 1 part by weight of the component (A) in the oral composition of the present disclosure include 3 to 70 parts by weight, more preferably 3 to 40 parts by weight. Furthermore, originally, when the content of the component (B) per 1 part by weight of the component (A) in the oral composition is 20 parts by weight or less, the problem of insolubility increases, and when the content of the component (B) per 1 part by weight of the component (A) is 16 parts by weight or less, the problem of insolubility becomes prominent. However, in the oral composition of the present disclosure, the component (A) can be effectively solubilized even in such a content ratio case. From such a viewpoint, preferred examples of the content of the component (B) per 1 part by weight of the component (A) in the oral composition of the present disclosure include 3 to 20 parts by weight, more preferably 3 to 16 parts by weight.

[0021] (C) Nonionic surfactant The oral composition of the present disclosure contains a nonionic surfactant as the component (C). In the oral composition of the present disclosure, the nonionic surfactant solubilizes glycyrrhetinic acids when co-formulated with ethanol and pyridoxines.

[0022] 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.

[0023] 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 solubilizing effect, it is preferably 12.0 to 15.5, and more preferably 13.0 to 15.0.

[0024] 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).

[0025] Nonionic surfactants with an HLB value of 11.0 to 16.0 include, specifically, 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; POE(20)POP(8) cetyl ether, POE(30)POP(6) decyltetradecyl ether, and POE(20)POP(6) decyl Examples include POE alkyl ethers such as tetradecyl ether; POE alkyl ethers such as POE(9) lauryl ether, POE(10) cetyl 3 ether, and POE(10) oleyl ether; polyglycerin fatty acid esters such as hexaglyceryl monolaurate and decaglyceryl monomyristate; POE glycerin fatty acid esters such as POE(15) glyceryl monooleate; and POE sorbitic acid fatty acid esters such as POE(60) sorbitic acid tetrastearate, POE(40) sorbitic acid tetraoleate, and POE(60) sorbitic acid tetraoleate. Here, "POE" is an abbreviation for polyoxyethylene and "POP" is an abbreviation for polyoxypropylene, and the number in parentheses after POE or POP is the average number of moles added.

[0026] In the oral composition of this disclosure, component (C) may be selected from the above nonionic surfactants and used alone, or two or more may be used in combination.

[0027] (C) Among the components, from the viewpoint of obtaining an even better solubilizing effect, POE hydrogenated castor oil is preferred, 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.

[0028] In the oral composition of this disclosure, the content of component (C) is not particularly limited and can be set appropriately according to the desired degree of solubilization effect. For example, it can be 0.1 to 10% by weight, and from the viewpoint of obtaining an even better solubilization effect, it is preferably 0.3 to 10% by weight, more preferably 0.5 to 10% by weight, and even more preferably 0.6 to 10% by weight. Furthermore, because the oral composition of this disclosure has an excellent solubilization effect, an effective solubilization effect can be obtained even with a small amount of nonionic surfactant. From this viewpoint, a suitable example of the content of component (C) in the oral composition of this disclosure is 0.1 to 7% by weight, more preferably 0.1 to 5% by weight, and even more preferably 0.1 to 3% by weight. Furthermore, while the problem of insolubility increases when the content of component (C) in an oral composition containing components (A) and (B) is 2.5% by weight or less, and the problem of insolubility becomes significant when the content of component (C) is 2% by weight or less, the oral composition of this disclosure effectively provides a solubilizing effect even when component (C) is present in such a content. From this viewpoint, preferred examples of the content of component (C) in the oral composition of this disclosure include 2.5% by weight or less, specifically 0.1 to 2.5% by weight, preferably 0.1 to 2% by weight, 0.1 to 1% by weight, 0.1 to 0.8% by weight, or 0.1 to 0.6% by weight.

[0029] In the oral composition of this disclosure, the ratio of component (A) to component (C) is not particularly limited and is determined according to the respective contents of component (A) and component (C) as described above. However, from the viewpoint of obtaining an even better solubilizing effect, the content of component (C) per 1 part by weight of component (A) 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, 30 to 200 parts by weight, or 50 to 200 parts by weight. Furthermore, because the oral composition of this disclosure has an excellent solubilizing effect, an effective solubilizing effect can be obtained even if the ratio of nonionic surfactant to component (A) is low. From this viewpoint, a preferred example of the content of component (C) per 1 part by weight of component (A) in the oral composition of this disclosure is 1 to 150 parts by weight. Furthermore, while the problem of insolubility increases when the content of component (C) per 1 part by weight of component (A) in the oral composition is 120 parts by weight or less, the problem of insolubility becomes significant when the content of component (C) per 1 part by weight of component (A) is 100 parts by weight or less, and the problem of insolubility becomes significantly significant when the content of component (C) per 1 part by weight of component (A) is 15 parts by weight or less, the oral composition of this disclosure can effectively obtain a solubilizing effect even at such content ratios. From this viewpoint, preferred examples of the content of component (C) per 1 part by weight of component (A) in the oral composition of this disclosure include 1 to 120 parts by weight, preferably 1 to 100 parts by weight, 1 to 50 parts by weight, 1 to 30 parts by weight, 1 to 20 parts by weight, more preferably 1 to 15 parts by weight, and 1 to 12 parts by weight.

[0030] (D) Pyridoxines The oral compositions of this disclosure contain pyridoxines as component (D). In the oral compositions of this disclosure, the pyridoxines are co-compounded with ethanol and a nonionic surfactant to solubilize glycyrrhetinic acids.

[0031] In this disclosure, pyridoxines are pyridoxine, pyridoxal, pyridoxamine, and salts thereof.

[0032] 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.

[0033] These pyridoxines may be used individually or in combination of two or more.

[0034] Among these pyridoxines, from the viewpoint of obtaining an even better solubilizing effect, pyridoxine or its salts are preferred, more preferably pyridoxine salts, and even more preferably pyridoxine hydrochloride salts.

[0035] In the oral compositions of this disclosure, the content of component (D) is not particularly limited and may be set appropriately according to the desired degree of solubilization effect. For example, it may be 0.005% by weight or more, and from the viewpoint of obtaining an even better solubilization effect, it is preferably 0.01% by weight or more, more preferably 0.015% by weight or more, and even more preferably 0.018% by weight or more. In the oral compositions of this disclosure, the content of component (D) is not particularly limited in terms of its upper limit, but for example, it may be 2% by weight or less, specifically 0.005 to 2% by weight, 0.005 to 1% by weight, 0.005 to 0.5% by weight, 0.005 to 0.1% by weight, and 0.005 to 0.05% by weight.

[0036] In the oral composition of this disclosure, the ratio of component (A) to component (D) is not particularly limited and is determined according to the respective contents of component (A) and component (D) as described above. However, from the viewpoint of obtaining an even better solubilizing effect, the content of component (D) per 1 part by weight of component (A) is 0.05 parts by weight or more, preferably 0.1 parts by weight or more, 0.2 parts by weight or more, 0.3 parts by weight or more, or 0.35% by weight or more. In the oral composition of this disclosure, the ratio of component (A) to component (D) is not particularly limited in terms of its upper limit, but for example, the content of component (D) per 1 part by weight of component (A) is 5 parts by weight or less, specifically 0.05 to 5 parts by weight, 0.05 to 3 parts by weight, 0.05 to 2 parts by weight, 0.05 to 1 part by weight, or 0.05 to 0.5 parts by weight.

[0037] (E)Water The oral compositions of this disclosure contain water as component (E). The content of component (E) in the oral compositions of this disclosure is not particularly limited, but examples include 30 to 90% by weight, preferably 35 to 80% by weight, more preferably 38 to 70% by weight, 38 to 60% by weight, 38 to 50% by weight, or 38 to 45% by weight.

[0038] Other ingredients The oral compositions of this disclosure may or may not contain, in addition to the components described above, pharmaceutically acceptable bases and / or additives as needed. Examples of such bases and additives, whether present or absent, include polyhydric alcohols, other surfactants, thickeners, chelating agents, pH adjusters, buffers, preservatives, antioxidants, stabilizers, antibacterial agents, anti-inflammatory agents, abrasives, glucosyltransferase (GTase) inhibitors, plaque inhibitors, desensitizing agents, calculus preventive agents, tooth strengthening / remineralizing agents, wetting agents, deodorants, fragrances, sweeteners, cooling agents, and pigments. When these additives are included in the oral compositions of this disclosure, their content may be appropriately determined depending on the type of base and / or additive used.

[0039] Among these base materials and / or additives, the oral compositions of this disclosure preferably contain polyhydric alcohols. Examples of polyhydric alcohols include dihydric alcohols such as propylene glycol, 1,3-butylene glycol, ethylene glycol, isoprene glycol, diethylene glycol, and dipropylene glycol; and trihydric alcohols such as glycerin. When the oral compositions of this disclosure contain polyhydric alcohols, the polyhydric alcohols may be used alone or in combination of two or more. When the oral compositions of this disclosure contain polyhydric alcohols, the polyhydric alcohols are preferably trihydric alcohols, and more preferably glycerin. When the oral compositions of this disclosure contain polyhydric alcohols, there are no particular restrictions on the content of the polyhydric alcohols, but for example, 30 to 70% by weight, preferably 40 to 65% by weight, and even more preferably 50 to 60% by weight are examples. In addition, in the oral compositions of this disclosure, the total amount of surfactants (other than component (C)) and component (C) is, for example, 0.1 to 10% by weight, 0.5 to 7% by weight, and more preferably 0.8 to 5.5% by weight.

[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] Because the oral compositions of this disclosure have excellent solubilizing effects, they are useful in ensuring the homogeneity of composition between lots during the preparation of oral compositions, and thus in achieving consistent quality control. Therefore, the appearance of the oral compositions of this disclosure does not need to be translucent and may be opaque.

[0043] Manufacturing method The oral compositions of this disclosure can be manufactured according to known formulation methods corresponding to their formulation form. [Examples]

[0044] The present disclosure will be explained in more detail below with reference to examples, but the present disclosure is not limited to these examples.

[0045] Test example Oral compositions (toothpastes) were prepared by mixing the components shown in Tables 2 and 3 in the indicated amounts. The HLB of POE hydrogenated castor oil 60 is 14.0. The solubility of the prepared oral compositions was evaluated on a 5-point scale, with 5 points indicating a clear appearance and 1 point indicating significant suspension due to glycyrrhetinic acid precipitation. Table 1 shows representative examples of scores of 5 (Example 1), 3 (Comparative Example 1), and 1 (Comparative Example 7). The results are shown in Tables 2 and 3. Furthermore, the solubilization effect is indicated by the number of "+" signs, which is the value obtained by subtracting the score of the composition without component (D) from the score in the examples. A higher number of "+" signs indicates a better solubilization effect. The results are shown in Table 3.

[0046] [Table 1]

[0047] [Table 2]

[0048] [Table 3]

[0049] As shown in Table 2, in aqueous oral compositions, component (A) exhibited poor solubility even when combined with components (B) and (C) (Comparative Examples 1-6), and this problem was not resolved even when a relatively large amount of component (C) was included (Comparative Examples 2, 3). In particular, solubility deteriorated significantly when the ratio of component (B) and / or component (C) to component (A) was low (Comparative Examples 4-6). Furthermore, in aqueous oral compositions, component (A) exhibited significantly poor solubility even when component (B) or (C) was not included (Comparative Examples 7, 8). On the other hand, when component (A) was combined with component (D) along with components (B) and (C) in aqueous oral compositions (Examples 1-6), component (A) became remarkably soluble, to the point that the aqueous oral composition became clear. In particular, even when the ratio of component (B) and / or component (C) to component (A) was low (Examples 3-6), where the solubility of component (A) inherently deteriorated significantly, a remarkably significant solubilizing effect was observed, to the point that the aqueous oral composition became clear.

[0050] Prescription examples Oral compositions (toothpastes) were prepared according to the formulations shown in Tables 4 and 5. All of the oral compositions exhibited excellent solubility of glycyrrhetinic acid.

[0051] [Table 4]

[0052] [Table 5]

Claims

1. An oral composition comprising (A) glycyrrhetinic acid, (B) ethanol, (C) nonionic surfactant, (D) pyridoxine, and (E) water.

2. The oral composition according to claim 1, wherein the content of component (B) per 1 part by weight of component (A) is 3 to 90 parts by weight.

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

4. The oral composition according to claim 1 or 2, wherein the content of component (D) per single portion of component (A) is 0.05 parts by weight or more.

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

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