Toothpaste composition

Abstract

The object of the present invention is to provide a stabilization technique for azulene derivatives in a toothpaste composition containing silica. [Solution] By adding hydroxyethylcellulose to a toothpaste composition containing an azulene derivative and silica at a ratio of 35 parts by weight or more per 1 part by weight of the azulene derivative, the stability of the azulene derivative is improved.

Description

Technical Field

[0001] The present invention relates to a dentifrice composition containing an azulene derivative.

Background Art

[0002] Azulene derivatives such as guaiazulene and guaiazulene sulfonate are known to have anti-inflammatory and epithelial tissue repair effects, and are widely used in aqueous compositions such as oral compositions, ophthalmic compositions, and topical compositions. However, since azulene derivatives become unstable in an aqueous solution, when they are formulated in an aqueous oral composition, they have a drawback of decomposing and decreasing over time.

[0003] Various means for stabilizing azulene derivatives in an aqueous composition have been proposed. Examples of such means include a technique of using a combination of organic acids and amino acids as a pH buffer for an azulene derivative-containing liquid preparation (Patent Document 1), a technique of incorporating berberines into an aqueous liquid preparation containing azulenes, polyvinylpyrrolidone and / or chondroitins (Patent Document 2), a technique of incorporating a water-soluble coloring substance into a preparation containing water-soluble azulene (Patent Document 3), and a technique of incorporating one or more nonionic surfactants selected from the group consisting of alkyl glycosides, polyoxyethylene hydrogenated castor oil, and sorbitan esters and a betaine acetate type surfactant into one or more azulene compounds selected from the group consisting of guaiazulene and guaiazulene sulfonate (Patent Document 4).

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

[0005] However, previous technologies have not addressed the stabilization of azulene derivatives incorporated into toothpaste compositions. The inventors unexpectedly encountered a problem in which the stability of azulene derivatives significantly decreased due to the presence of silica in the toothpaste composition when azulene derivatives were incorporated into the toothpaste composition. Therefore, the above-mentioned technologies do not provide sufficient stabilization for azulene derivatives in toothpaste compositions containing silica.

[0006] Therefore, the object of this disclosure is to provide a stabilization technique for azulene derivatives in a toothpaste composition containing silica. [Means for solving the problem]

[0007] The inventors of the present invention conducted diligent research to solve the aforementioned problems and discovered that the stability of the azulene derivative is improved by incorporating hydroxyethylcellulose in a predetermined proportion into a toothpaste composition containing an azulene derivative and silica. The present invention was completed by further research based on this finding.

[0008] In other words, this disclosure provides inventions in the following embodiments. Item 1. A toothpaste composition comprising (A) an azulene derivative, (B) silica, (C) hydroxyethylcellulose, and (D) water, wherein the content of component (C) is 35 parts by weight or more per 1 part by weight of component (A). Item 2. The toothpaste composition according to Item 1, wherein the content of component (A) is 0.001 to 0.02% by weight. Item 3. The toothpaste composition according to item 1 or 2, wherein the content of component (B) is 2 to 45% by weight. Item 4. A toothpaste composition according to any one of items 1 to 3, wherein the pH is 7 or higher. Item 5. The toothpaste composition according to any one of claims 1 to 4, wherein the content of (D) is 10 to 35% by weight. [Effects of the Invention]

[0009] This disclosure provides a stabilization technique for azulene derivatives in a toothpaste composition containing silica. [Modes for carrying out the invention]

[0010] The toothpaste composition of this disclosure contains (A) an azulene derivative (hereinafter also referred to as "component (A)"), (B) silica (hereinafter also referred to as "component (B)"), (C) hydroxyethylcellulose (hereinafter also referred to as "component (C)"), and (D) water (hereinafter also referred to as "component (D)"), characterized in that the content of component (C) per 1 part by weight of component (A) is 35 parts by weight or more. The toothpaste composition of this disclosure will be described in detail below. In this specification, numerical ranges indicated by two numbers and "~" include those two numbers as the lower limit and upper limit. For example, the notation 2~15% by weight means 2% by weight or more and 15% by weight or less.

[0011] (A) Azulene derivatives The toothpaste composition of this disclosure contains an azulene derivative as component (A). Although the stability of azulene derivatives is significantly reduced when incorporated into aqueous toothpaste compositions containing silica, the azulene derivative is stabilized in the toothpaste composition of this disclosure.

[0012] The azulene derivatives used in this disclosure are compounds and salts thereof in which azulene is bonded to one or more substituents selected from the group consisting of acidic functional groups and alkyl groups. Examples of acidic functional groups include sulfo groups and carboxyl groups. Examples of alkyl groups include alkyl groups having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, and more preferably 1 to 3 or 1 to 2 carbon atoms.

[0013] Specific examples of azulene derivatives include azulene sulfonic acid (guaiazulene sulfonic acid), dimethylisopropylazulene (guaiazulene), 1,4-dimethyl-7-ethylazulene (chamazulene), and 1,4-dimethyl-7-ethylazulene-3-sulfonic acid (chamazulene sulfonic acid).

[0014] When azulene derivatives are in the form of salts, the type of salt is not particularly limited, as long as it is pharmaceutically or physiologically acceptable. Examples include alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts and magnesium salts; other metal salts such as aluminum salts; ammonium salts; carboxylate salts such as acetate, trifluoroacetate, butyrate, palmitate, stearate, fumarate, maleate, succinate, malonate, lactate, tartrate, and citrate; organic sulfonates such as methanesulfonate, toluenesulfonate, and tosylate; organic amine salts such as methylamine salt, triethylamine salt, triethanolamine salt, morpholine salt, piperazine salt, pyrrolidine salt, tripyridine salt, and picoline salt; and inorganic salts such as hydrochloride, sulfate, nitrate, hydrobromide, and phosphate.

[0015] These azulene derivatives may be used individually or in combination of two or more.

[0016] Among these azulene derivatives, preferred are compounds and salts thereof in which at least one or more acidic functional groups are bonded to the azulene skeleton; more preferably are compounds and salts thereof in which at least one or more sulfo groups are bonded to the azulene skeleton; even more preferably are azulene sulfonic acid and salts thereof; even more preferably are alkali metal salts of azulene sulfonate; and particularly preferably is sodium azulene sulfonate.

[0017] In the toothpaste composition of this disclosure, the content of component (A) is not particularly limited, but for example, it is 0.001 to 0.02% by weight, preferably 0.01 to 0.02% by weight.

[0018] (B) Silica The dentifrice composition of the present disclosure contains silica as component (B). When silica is incorporated into an aqueous dentifrice composition containing an azulene derivative, the stability of the azulene derivative is significantly reduced. However, in the dentifrice composition of the present disclosure, the azulene derivative is stabilized while containing silica.

[0019] The silica used in the present disclosure is silicon dioxide. Silica is a known component having a thickening effect and / or a removing effect in a dentifrice composition. Examples of silica include anhydrous silicic acid and hydrous silicon dioxide.

[0020] These silicas may be used alone or in combination of two or more. Among these silicas, anhydrous silicic acid is preferably mentioned.

[0021] In the dentifrice composition of the present disclosure, the content of component (B) is not particularly limited, and examples thereof include 2 to 45% by weight. From the viewpoint of enhancing the stabilizing effect of component (A), the content of component (B) is preferably 2 to 35% by weight, more preferably 2 to 30% by weight, still more preferably 2 to 25% by weight, and even more preferably 2 to 22% by weight. Further, since the dentifrice composition of the present disclosure is excellent in the stabilizing effect of component (A), even if the content of component (B) is relatively high, component (A) can be effectively stabilized. From this viewpoint, suitable contents of component (B) include 7 to 45% by weight, 10 to 45% by weight, 15 to 45% by weight, or 18 to 45% by weight.

[0022] In the toothpaste composition of this disclosure, the ratio of component (A) to component (B) is determined by the content of each component as described above. However, from the viewpoint of enhancing the stabilizing effect of component (A), the content of component (B) per 1 part by weight of component (A) is preferably 250 to 5000 parts by weight, more preferably 250 to 4000 parts by weight, even more preferably 250 to 3000 parts by weight, even more preferably 250 to 2500 parts by weight, 250 to 2000 parts by weight, 250 to 1500 parts by weight, or 250 to 1200 parts by weight. Furthermore, since the toothpaste composition of this disclosure has an excellent stabilizing effect on component (A), component (A) can be effectively stabilized even if the ratio of component (B) to component (A) is relatively high. From this perspective, suitable content of component (B) per 1 part by weight of component (A) includes 300 to 5000 parts by weight, 500 to 5000 parts by weight, 700 to 5000 parts by weight, or 900 to 5000 parts by weight.

[0023] (C) Hydroxyethylcellulose The toothpaste composition of this disclosure contains hydroxyethylcellulose as component (C). In aqueous toothpaste compositions containing an azulene derivative together with silica, the stability of the azulene derivative is significantly reduced. However, in the toothpaste composition of this disclosure, the azulene derivative is stabilized by the inclusion of hydroxyethylcellulose, even though it is an aqueous toothpaste composition containing an azulene derivative together with silica.

[0024] The viscosity of hydroxyethylcellulose is not particularly limited, but in a 1% by mass aqueous solution (25°C), for example, it is 500 mPa·s or more, preferably 800 to 10000 mPa·s, more preferably 1000 to 5000 mPa·s, even more preferably 1200 to 3000 mPa·s, and even more preferably 1400 to 2000 mPa·s or 1500 to 1800 mPa·s. The viscosity is the value measured using a Type B viscometer "TOKI SANGYO VISCOMETER TVB-10" (manufactured by Toki Sangyo Co., Ltd.) with rotor: M3 (rotation speed: 30 rpm).

[0025] In the toothpaste composition of this disclosure, the ratio of component (A) to component (C) is 35 parts by weight or more, in terms of the content of component (C) per 1 part by weight of component (A). From the viewpoint of enhancing the stabilizing effect of component (A), the content of component (C) per 1 part by weight of component (A) is preferably 38 parts by weight or more, more preferably 65 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 examples include 500 parts by weight or less, 400 parts by weight or less, 300 parts by weight or less, 200 parts by weight or less, 100 parts by weight or less, 70 parts by weight or less, or 50 parts by weight or less.

[0026] In the toothpaste composition of this disclosure, the specific content of component (C) is determined according to the content of component (A) and the ratio of component (A) and component (C) as described above, but from the viewpoint of enhancing the stabilizing effect of component (A), preferably it is 0.2% by weight or more, preferably 0.5% by weight or more, more preferably 0.7% by weight or more, 1% by weight or more, or 1.3% by weight or more. The specific content of component (C) is not particularly limited in terms of its upper limit, but examples include 10% by weight or less, 5% by weight or less, 3% by weight or less, 2% by weight or less, 1.5% by weight or less, or 1% by weight or less.

[0027] (D)Water The toothpaste composition of this disclosure contains water as component (D). Although water destabilizes azulene derivatives, the azulene derivatives are stabilized in the toothpaste composition of this disclosure.

[0028] In the toothpaste composition of this disclosure, the content of component (D) is not particularly limited, but for example, it is 10 to 35% by weight. From the viewpoint of enhancing the stabilizing effect of component (A), it is preferably 10 to 30% by weight, more preferably 10 to 27% by weight, 10 to 26% by weight, or 10 to 25% by weight. Furthermore, since the toothpaste composition of this disclosure has an excellent stabilizing effect of component (A), component (A) can be effectively stabilized even if the content of component (D) is relatively high. From this viewpoint, suitable content of component (D) is 15 to 35% by weight, 18 to 35% by weight, 21 to 35% by weight, or 23 to 35% by weight.

[0029] In the toothpaste composition of this disclosure, the ratio of component (A) to component (D) is determined by the content of each component as described above, but for example, it can be 800 to 4000 parts by weight. From the viewpoint of enhancing the stabilizing effect of component (A), the content of component (D) per 1 part by weight of component (A) is preferably 800 to 3500 parts by weight, more preferably 800 to 3000 parts by weight, even more preferably 800 to 2500 parts by weight, 800 to 2000 parts by weight, 800 to 1500 parts by weight, 800 to 1400 parts by weight, or 800 to 1300 parts by weight. Furthermore, since the toothpaste composition of this disclosure has an excellent stabilizing effect on component (A), component (A) can be effectively stabilized even if the ratio of component (D) to component (A) is relatively high. From this perspective, suitable content of component (D) per 1 part by weight of component (A) includes 900 to 4000 parts by weight, 1000 to 4000 parts by weight, 1100 to 4000 parts by weight, or 1200 to 4000 parts by weight.

[0030] Other ingredients In addition to the components described above, the toothpaste composition 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 this disclosure. Examples of such optional components include preservatives, bactericides, antibacterial agents, anti-inflammatory agents, abrasives (other than component (B) above), thickeners (other than component (B) and component (C) above), glucosyltransferase (GTase) inhibitors, plaque inhibitors, desensitizing agents, tartar preventives, tooth structure strengthening / remineralizing agents, local anesthetics, blood circulation promoters, humectants, sweeteners, dyes / pigments, deodorants, surfactants, monohydric lower alcohols, buffers, pH adjusters, and the like.

[0031] Examples of disinfectants include cationic antibacterial agents [bisguanides (chlorhexidines such as chlorhexidine gluconate, alexidine, etc.), quaternary ammonium salts (cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, depotassium chloride, domiphene bromide, etc.)], hinokitiol, etc.

[0032] 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).

[0033] 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.

[0034] Examples of pigments / colorants include titanium dioxide.

[0035] Examples of surfactants include anionic surfactants, nonionic surfactants, and amphoteric surfactants. Examples of anionic surfactants include salts of alkyl sulfate esters such as lauryl sulfate, myristyl sulfate, cetyl sulfate, and oleyl sulfate; salts of higher fatty acid amide sulfonic acids such as lauroyl methyl taurine, myristoyl methyl taurine, coconut oil fatty acid methyl taurine, and lauryl methyl taurine; salts of α-olefin sulfonic acids; salts of N-acyl amino acids such as N-myristoyl glutamic acid, cocoyl glutamic acid, N-lauroyl glutamic acid, N-stearoyl glutamic acid, and cocoyl glycine; salts of alkylbenzene sulfonic acids such as dodecylbenzenesulfonic acid; salts of polyoxyethylene alkyl ether sulfate esters such as polyoxyethylene lauryl ether sulfate; and salts of N-acyl sarcosinic acid such as lauroyl sarcosine. 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 salts.

[0036] Examples of monohydric lower alcohols include monohydric alcohols with 2 to 5 carbon atoms, specifically ethanol, propanol, isopropanol, and butanol.

[0037] A preferred example of a toothpaste composition of this disclosure may include, as other components, one or more of alkali metal fluorides, fluorophosphates, and / or salts of fluorophosphates (preferably salts of fluorophosphates, more preferably alkali metal salts of fluorophosphates, even more preferably alkali metal salts of monomonofluorophosphates, and even more preferably sodium monofluorophosphate); polyhydric alcohols (preferably glycerin); sugar alcohols (preferably sorbitol); titanium dioxide; surfactants [preferably anionic surfactants (preferably salts of alkyl sulfates, more preferably lauryl sulfates, and even more preferably sodium lauryl sulfate); nonionic surfactants (preferably polyoxyethylene hydrogenated castor oil)]; and monohydric lower alcohols (preferably ethanol).

[0038] If the toothpaste composition of this disclosure contains alkali metal fluorides, fluorophosphates, and / or salts of fluorophosphates, the 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 in total. If the toothpaste composition of this disclosure contains polyhydric alcohols, the content of such components may be, for example, 1 to 75% by weight, preferably 10 to 55% by weight, and even more preferably 20 to 40% by weight. If the toothpaste composition of this disclosure contains sugar alcohols, the content of such components may be, for example, 0.1 to 25% by weight, preferably 1 to 25% by weight, and more preferably 10 to 20% by weight. If the toothpaste composition of this disclosure contains titanium dioxide, the content of such components may be, for example, 0.1 to 3% by weight, preferably 0.5 to 2% by weight. If the toothpaste composition of this disclosure contains a surfactant, the content of the component may be, for example, 0.05 to 20% by weight, preferably 0.5 to 15% by weight, more preferably 2 to 6% by weight [if an anionic surfactant is included, the content of the component may be, for example, 0.001 to 5% by weight, preferably 0.01 to 3% by weight, more preferably 0.8 to 2% by weight; if a nonionic surfactant is included, the content of the component may be, for example, 0.01 to 15% by weight, preferably 0.1 to 10% by weight, more preferably 1 to 5% by weight]. If the toothpaste composition of this disclosure contains a monohydric lower alcohol, the content of the component may be, for example, 0.001 to 15% by weight, preferably 0.01 to 10% by weight, more preferably 0.1 to 5% by weight, and even more preferably 0.5 to 2% by weight.

[0039] In preferred examples of the toothpaste compositions of this disclosure, one or more of the above-mentioned components, such as cationic antibacterial agents, hinokitiol, phosphocholine group-containing polymers, and amphoteric surfactants, are not included as other components.

[0040] pH The pH of the toothpaste composition of this disclosure can be selected without particular limitation from the pH ranges generally applied to toothpaste compositions, but examples include 7 or higher, more specifically 7.00 to 8.50, preferably 7.00 to 8.30, more preferably 7.00 to 7.99, even more preferably 7.00 to 7.95, 7.30 to 7.95, 7.50 to 7.95, 7.60 to 7.95, or 7.70 to 7.95. In this disclosure, the pH of the toothpaste composition is a value measured at a temperature of 25°C. To adjust the pH to the ranges described above, buffering agents, pH adjusters, etc., can be used.

[0041] Dosage form / form The dosage form of the toothpaste composition of this disclosure is not particularly limited, as long as it can be applied in the oral cavity. For example, it may be liquid or semi-solid (gel-like, paste-like), but semi-solid is preferred.

[0042] The form of the toothpaste 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, but examples include liquid toothpaste and paste toothpaste, and paste toothpaste is preferred. [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 Paste-type toothpastes (toothpastes) with the compositions shown in Tables 1 and 2 were prepared. The viscosity of the 1% by mass aqueous solution (25°C) of hydroxyethylcellulose used was measured by the following method and was 1680 mPa·s in both cases. Viscosity measurement conditions Type B Viscometer: "TOKISANGYOVISCOMETERTVB-10" (manufactured by Toki Sangyo Co., Ltd.) Rotor: M3 Rotation speed: 30 rpm

[0045] Approximately 40g of the resulting toothpaste paste was filled into an aluminum laminate tube, sealed, and stored at 60°C for 3 weeks. The sodium azulene sulfonate content in the toothpaste paste before and after storage was measured by high-performance liquid chromatography, and the percentage of the content after storage, with the content before storage set to 100%, was determined as the residual rate. The residual rate was also scored based on the following classification. A higher score indicates a higher stabilizing effect of the azulene derivative. 98.0% or higher 10 96.5% or more and less than 98.0% 9 95.0% or more and less than 96.5% 8 93.5% or more and less than 95.0% 7 92.0% or more and less than 93.5% 6 90.5% or more and less than 92.0% 5 89.0% or more and less than 90.5% 4 87.5% or more and less than 89.0% 3 86.0% or more and less than 87.5% 2 Less than 86.0% 1

[0046] [Table 1]

[0047] [Table 2]

[0048] As shown in Table 1, compared to the residual rate of component (A) in the toothpaste composition containing components (A) and (D) (Comparative Example 1), the stability of component (A) deteriorated significantly when component (B) was further added to the toothpaste composition containing components (A) and (D) (Comparative Example 2). On the other hand, when component (C) was further added to the toothpaste composition containing components (A), (B), and (D) in a ratio of 35 parts by weight or more per 1 part by weight of component (A) (hereinafter also referred to as the "predetermined ratio") (Examples 1 to 4), the stability of component (A) improved significantly. However, when a component used as a thickener similar to component (C) was added instead of component (C) (Comparative Examples 3 and 4), the stability of component (A) could not be effectively improved.

[0049] Furthermore, as shown in Table 2, in toothpaste compositions containing components (A), (B), (C), and (D), when component (C) was not included in the predetermined ratio (Comparative Examples 5 and 6), the stability of component (A) could not be effectively improved. In contrast, in toothpaste compositions containing components (A), (B), (C), and (D), when component (C) was included in the predetermined ratio (Examples 5 to 8), the stability of component (A) was significantly improved. However, when a component used as a thickener similar to component (C) was added instead of component (C) (Comparative Examples 7 to 9), the stability of component (A) could not be effectively improved.

[0050] Prescription examples Toothpaste compositions (paste-type toothpastes) with the formulations shown in Table 3 were prepared. The pH was adjusted to 7.70 to 7.95. In all of the toothpaste compositions, which contained sodium azulene sulfonate and anhydrous silicic acid together with water, a predetermined ratio of hydroxyethyl cellulose relative to sodium azulene sulfonate was added, resulting in an excellent stabilization effect of sodium azulene sulfonate.

[0051] [Table 3]

Claims

1. A toothpaste composition comprising (A) an azulene derivative, (B) silica, (C) hydroxyethylcellulose, and (D) water, wherein the content of component (C) is 35 parts by weight or more per 1 part by weight of component (A).

2. The toothpaste composition according to claim 1, wherein the content of component (A) is 0.001 to 0.02% by weight.

3. The toothpaste composition according to claim 1 or 2, wherein the content of component (B) is 2 to 45% by weight.

4. The toothpaste composition according to claim 1 or 2, wherein the pH is 7 or higher.

5. The toothpaste composition according to claim 1 or 2, wherein the content of (D) is 10 to 35% by weight.

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