JP4893124B2 - Liquid oral composition - Google Patents

Description

  The present invention has good usability and storage stability, exhibits a thickening effect due to calcium ions when applied to the oral cavity, and is further excellent in improving the retention in the oral cavity of a medicinal component. It is related with the composition for liquid oral cavity suitable for the interdental part applied by this, or the cervical part or gingival application applied by a finger.

  Conventionally, water-soluble polymers have been used for the purpose of toothpaste binders, liquid composition thickeners and viscosity modifiers, food stabilizers, etc. Examples thereof include sodium carboxymethyl cellulose (hereinafter abbreviated as CMC).

  Alginic acid is a hydrophilic polymer obtained by extracting and purifying brown algae such as Kajime, Alame, Kelp, Macrosystemis, Ascophyllum, Echronia Maxima, and Lessonia, and is chemically β- 1,4-bonded D-mannuronic acid [M] and α-1,4-bonded L-guluronic acid [G], wherein the polymerization degree of alginic acid and intramolecular D-mannuronic acid and L- The content ratio of guluronic acid (hereinafter abbreviated as M / G ratio) varies depending on the type and part of the raw material, the extraction method, and the like.

  CMC is a water-soluble polymer compound in which caustic soda is made to act on cellulose to produce alkali cellulose (alkalization), monochloroacetic acid reacts with this (etherification), and a carboxymethyl group is introduced into the hydroxyl group of cellulose. The degree of etherification in which the three hydroxyl groups per cellulose unit are substituted with carboxymethyl groups varies depending on the preparation method.

  As a technique for blending alginic acid or a salt thereof into a liquid oral composition such as a mouthwash or a liquid dentifrice, a composition that suppresses the formation of plaque by sodium alginate (Patent Document 1: JP-A-1-213222), By blending alginic acid having an M / G ratio of 0.2 to 1 or a salt thereof, the formation of dental plaque is suppressed, and further by blending alginic acid or a salt thereof having an average degree of polymerization of 800 to 1,500. In a composition having an excellent effect of inhibiting bacterial adhesion (Patent Document 2: JP-A-4-36228) or an oral composition containing triclosan, the mass ratio of mannuronic acid to guluronic acid (M / G ratio) A composition in which the retention in the oral cavity of triclosan is improved by blending a water-soluble polymer such as alginic acid having a salt of 1 or less and salts thereof (Patent Document 3: Japanese Patent Laid-Open No. Hei 4-) 39118), a composition in which oral retention of menthol is improved by blending sodium alginate into a mouthwash solution containing no abrasive (Patent Document 4: JP-A-8-333227), containing an abrasive Liquid composition comprising 50 to 55% by weight of sorbitol and an alginate as a suspending agent blended in the liquid composition (Patent Document 5: JP-T 9-510192), tara gum and sodium alginate A liquid oral composition (Patent Document 6: Japanese Patent Application Laid-Open No. 2004-217570) having a high cleaning feeling and improved palatability by suppressing stickiness after mouthwashing is known. Yes.

  Further, as a composition in which sodium alginate and CMC are used in combination, a composition in which sodium alginate and a specific CMC are blended to increase the oral residue of pyrithiones (Patent Document 7: JP-A-2001-322922), M A composition in which an alginate having a / G ratio of 0.2 to 1 and CMC is blended (Patent Document 2: JP-A-4-36228, described in Example 1) is known.

  However, liquid orally using alginic acid or a salt thereof having a medium viscosity to high viscosity (specifically, a viscosity at 20 ° C. of about 200 to 500 mPa · s), which has been conventionally used for oral products such as toothpaste, as a viscosity modifier. When the composition is used for a composition, the viscosity of the liquid oral composition is remarkably reduced during storage, and in particular, a composition that does not contain a pH adjuster and the pH is not maintained near neutral is stored during storage. Viscosity is significantly reduced, which is a major problem in the quality of the preparation.

  Furthermore, when a liquid composition containing sodium alginate and CMC does not contain an appropriate amount of phosphate or citrate, water-soluble polymer precipitates during storage, and an appropriate viscosity does not develop. A big problem occurs.

  Also known is an acidic oral composition (patent document 8: Japanese translations of PCT publication No. 2002-524401) in which a viscosity-adjusting polymer substance such as alginate is blended and the effective pH is adjusted to 4.5 or less. . However, when the pH of the liquid composition containing an alginate is lower than 6.0 as described above, the viscosity is remarkably lowered, which causes a serious problem in quality. Furthermore, a dentifrice composition (Patent Document 9: JP 2001-302476 A) containing ascorbic acid or an ascorbic acid derivative and alginic acid or a salt thereof and having a pH of 8.0 or more is known. However, in a liquid composition containing alginic acid or a salt thereof and having a pH of 8.0 or more, there are significant quality problems such as significant coloration or discoloration during storage or harmful effects on the oral mucosa. It becomes.

  On the other hand, alginic acid or a salt thereof is generally known to gel (thicken) by a cross-linking reaction with metal ions such as calcium, but this function is utilized to retain medicinal ingredients in the oral cavity. Is possible. The gelation ability and gel strength of alginic acid are greatly influenced by the content ratio and arrangement of D-mannuronic acid [M] and L-gluconic acid [G]. When the G ratio is high, the gel strength is high. (Non-Patent Document 1: FRAGRANCE JOURNAL 1994-4, 76-84). Regarding the influence of molecular weight, it is also known that when the M / G ratio, concentration, and G content are the same, the gelling ability and gel strength increase as the molecular weight increases. As a composition characterized by the gelation ability of alginic acid, a technique of blending an alginic acid derivative having an M / G ratio of 1.0 or less with phosphoric acid and a salt thereof is known. This is a technique in which thickening of a composition occurs when it comes into contact with a biological fluid such as saliva or saliva, and the retention of medicinal components at an application site is possible (Patent Document 10: JP 2002-332248 A). ). Further, a mouthwash composition in which sodium alginate and phosphate are blended in a mouthwash without an abrasive (Patent Document 4: JP-A-8-333227, described in Examples 20 and 21), water-soluble phosphoric acid A mouthwash composition that improves the dispersion stability of the abrasive and exhibits an excellent cleaning effect by blending one or more of a hydrogen compound, a hydrogen carbonate compound, and a hydrogen sulfate compound (Patent Document 11: Special Kaihei 10-167940) is known.

  However, it is possible to suppress a decrease in the viscosity of the liquid composition to some extent by blending a phosphate with a liquid composition containing alginic acid or a salt thereof and maintaining the formulation pH in the vicinity of neutrality. When a high-viscosity alginic acid or a salt thereof is used, a decrease in viscosity during storage cannot be completely suppressed, resulting in a serious quality problem.

  Furthermore, when a high concentration of phosphate is added to a liquid composition containing alginic acid or a salt thereof, gelation (thickening) of the composition does not occur when applied to the oral cavity. The retention of medicinal components cannot be sufficiently increased.

  For example, when a low viscosity alginic acid having a viscosity at 20 ° C. of about 5 to 100 mPa · s or a salt thereof is used alone, in order to give the composition an appropriate viscosity, the alginic acid is used. Or it is necessary to mix | blend the salt with high concentration. However, in a composition in which such alginic acid or a salt thereof is excessively present, gelation (thickening) upon application to the oral cavity is remarkably inhibited or does not develop. As a result, the retention of the medicinal component in the oral cavity cannot be improved satisfactorily.

  Further, a mouthwash composition in which sodium alginate, citric acid, and citrate are blended in a mouthwash solution containing no abrasive (Patent Document 4: JP-A-8-333227, Examples 6, 14-17, 21) Description), a composition comprising alginic acid or an salt thereof having an average M / G ratio of 0.2 to 1 and a water-soluble polyphosphoric acid (Patent Document 12: JP-A-5-39213), an average molecular weight of 1,000 Composition comprising ˜100,000 anionic polysaccharide such as sodium alginate and polyphosphate (Patent Document 13: JP-A-8-40859), water-soluble polyphosphate, orthophosphate and amphoteric surfactant A liquid toothpaste (see Patent Document 14: JP-A-9-12437, Example 5) in which alginic acid or a salt thereof is blended as a binder in a composition obtained by blending is known. In enoic acid or composition containing a high concentration of a salt or polyphosphate, gelling (thickening) is or are significantly inhibited, or may not express. As a result, the retention of the medicinal component in the oral cavity cannot be improved satisfactorily.

  Further, a composition containing an anionic polysaccharide such as sodium alginate having an average molecular weight of 1,000 to 100,000 and a divalent metal ion such as magnesium and zinc ions (Patent Document 15: JP-A-9-175968) However, a composition containing such a divalent metal ion has a characteristic in that it is partially gelled during storage or is prone to drought, or has an appearance stability. It becomes a big problem.

  As described above, alginic acid or a salt thereof is known to exhibit an effect of suppressing plaque formation, an effect of improving the retention in the oral cavity of medicinal components, and the like by blending it into the oral composition. There were problems with the usability and storage stability of the preparation, and it was difficult to say that the retention in the oral cavity of the medicinal component was sufficiently satisfactory.

JP-A-1-213222 JP-A-4-36228 JP-A-4-139118 JP-A-8-333227 JP-T 9-510192 JP 2004-217570 A JP 2001-322922 A Special Table 2002-524401 JP 2001-302476 A JP 2002-332248 A Japanese Patent Laid-Open No. 10-167940 Japanese Patent Laid-Open No. 5-39213 JP-A-8-40859 Japanese Patent Laid-Open No. 9-12437 JP-A-9-175968 FRAGRANCE JOURNAL 1994-4, 76-84

  The present invention has been made in view of the above circumstances, has good usability and storage stability, sufficiently exhibits a thickening effect due to calcium ions, and further sufficiently improves the retention in the oral cavity of medicinal components. An object of the present invention is to provide a liquid composition for oral cavity that can be demonstrated in the above.

As a result of studying the liquid oral composition containing an alginate in order to achieve the above object, the present inventor has a viscosity of a 1.0 mass% aqueous solution at 20 ° C. of 5 to 100 mPa · s. Low viscosity alginate and the following general formula (1)
_{M n H 3-n PO 4} (1)
(However, M represents Na or K, and n is 1, 2 or 3.)
It was found that a decrease in viscosity can be effectively suppressed even under high temperature storage by adding a phosphate represented by the formula (II) and adjusting the pH at 25 ° C. to a range of 6.0 to 8.5.

  Furthermore, in a composition in which a low-viscosity alginate alone is blended as such a viscosity modifier, when applied to the oral cavity, a thickening effect by a crosslinking reaction with a divalent metal ion such as calcium (hereinafter referred to as Ca ion). It is abbreviated as thickening effect.) Although it is sufficiently exerted, the viscosity of the preparation is too low, making it difficult to put the appropriate amount of preparation on a toothbrush, etc., or dripping down before the preparation is transported to the application site In addition, when a low-viscosity alginate is blended at a high concentration to give the desired viscosity, the above usability problem is improved. In the composition containing a salt at a high concentration, the thickening effect due to Ca ions is not sufficiently exhibited, and further, the improvement effect on the retention in the oral cavity of the medicinal component is not sufficiently exhibited.

Accordingly, the present inventor has solved the above-mentioned problems, and in a liquid oral composition containing a low-viscosity alginate, the usability and storage stability are good, and an excellent thickening effect by Ca ions is exhibited. Furthermore, in order to develop a composition that sufficiently exhibits the effect of improving the retention of medicinal components in the oral cavity, as a result of further intensive studies, (A) the viscosity of a 1.0 mass% aqueous solution at 20 ° C. is 5 An alginate having a content ratio (M / G ratio) of 0.5 to 2.0 (mass ratio) of D-mannuronic acid [M] and L-guluronic acid [G] in the molecule of ˜100 mPa · s, (B) Sodium carboxymethylcellulose having a degree of etherification of 0.8 to 1.6, (C) the following general formula (1)
_{M n H 3-n PO 4} (1)
(However, M represents Na or K, and n is 1, 2 or 3.)
And (D) water is added, and the pH at 25 ° C. is in the range of 6.0 to 8.5. 0.5 to 2.0% by mass, (B) 0.2 to 1.2% by mass of sodium carboxymethylcellulose, and (C) 0.05% of the phosphate represented by the above general formula (1). -0.5% by mass, (D) the water content is 45-90% by mass, and the mass ratio of the component (A) / (B) is in the range of 0.5-6.0. Therefore, when it is applied to the oral cavity, the usability and storage stability are good, and an excellent thickening effect due to Ca ions is expressed. Further, when a medicinal component is blended, the medicinal component is improved in the retention in the oral cavity. And found that a liquid oral composition capable of fully exhibiting It came to be.

Therefore, the present invention
(A) The viscosity of a 1.0 mass% aqueous solution at 20 ° C. is 5 to 100 mPa · s, and the content ratio of the D-mannuronic acid [M] and L-guluronic acid [G] in the molecule (M / G ratio) alginate and 0.5 to 2.0 wt% is but 0.5 to 2.0 in mass ratio,
(B) 0.2 to 1.2% by mass of sodium carboxymethyl cellulose having a degree of etherification of 0.8 to 1.6
And (A) component / (B) component as a mass ratio in the range of 0.5 to 6.0,
(C) The following general formula (1)
_{M n H 3-n PO 4} (1)
(However, M represents Na or K, and n is 1, 2 or 3.)
0.05 to 0.5% by mass of a phosphate represented by
(D) 45-90 mass% of moisture
Compounded, pH at 25 ° C. of the composition in the range of 6.0 to 8.5, to provide a liquid oral composition, wherein the viscosity at 25 ° C. is 600~3,400mPa · s.

In this case, the liquid oral composition of the present invention further comprises (F) a fluorine compound selected from sodium fluoride and sodium monofluorophosphate and / or (G-1) tranexamic acid, epsilon aminocaproic acid, glycyrrhizinate. And (G-2) a poorly water-soluble anti-inflammatory agent selected from glycyrrhetinic acid and dl-α-tocophenol acetate and / or (H ) Containing a disinfectant selected from isopropylmethylphenol, triclosan, hinokitiol, cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, chlorhexidine gluconate, chlorhexidine hydrochloride, and (I) a nonionic surfactant and / or (J ) It is preferable to contain ethanol.
In addition, the liquid oral composition of the present invention is preferably prepared as an interdental product applied by an interdental brush, or a cervical or gingival application product applied by a finger.

  The liquid oral composition of the present invention has excellent usability (dischargeability, retention), storage stability (appearance, pH, viscosity), and exhibits a thickening effect by Ca ions when applied to the oral cavity. In addition, when a medicinal component is blended, the medicinal component is highly effective in improving the retention in the oral cavity, and is sufficiently exerted. Especially, it is applied by an interdental product or finger applied by an interdental brush. It is useful as a product for cervical or gingival application.

Hereinafter, the present invention will be described in more detail. The liquid oral composition of the present invention is
(A) alginate,
(B) sodium carboxymethylcellulose,
(C) phosphate,
(D) It contains water as an essential component, and more preferably,
(E) xanthan gum,
(F) Fluorine compound selected from sodium fluoride and sodium monofluorophosphate (G) Anti-inflammatory agent (H) Bactericide (I) Nonionic surfactant (J) Ethanol.

  Here, specific examples of the alginate of the component (A) include alkali metal salts such as sodium salt and potassium salt of alginic acid, ammonium salts, and the like. The alginate is preferably water-soluble. In particular, it is a water-soluble alkali metal alginate, and commercially available sodium alginate and potassium alginate are preferably used, and sodium alginate is more preferably used.

  Examples of sodium alginate and potassium alginate are commercially available from Kibun Food Chemifa Co., Ltd., Kimika Co., Ltd., Fuji Chemical Industry Co., Ltd., Kelco, Sigma, PRONOVA biopolymer, and the like.

  The alginate of the component (A) in the liquid oral composition of the present invention has a usability of discharging an appropriate amount from a container or holding it on an interdental brush or a finger, storage stability of the preparation (appearance, pH, viscosity) and the effect of thickening by Ca ions, and further the effect of improving the retention of medicinal components in the oral cavity, the viscosity of a 1.0 mass% aqueous solution at 20 ° C. is a Brookfield viscometer (BM type viscometer). , Rotor No. 1, measured at 30 rpm, after 60 seconds of rotation), it is 5 to 100 mPa · s, preferably 8 to 50 mPa · s, more preferably 10 to 30 mPa · s. . When the viscosity exceeds 100 mPa · s, the effect of increasing the viscosity by Ca ions is excellent. However, since the decomposition at high temperature storage occurs remarkably, it causes a problem in appearance stability and viscosity stability. Moreover, the thing less than 5 mPa * s cannot fully exhibit the thickening effect by Ca ion, and also does not exhibit the sufficient improvement effect in the oral cavity retention property of a medicinal component.

  Furthermore, the alginate in the present invention has an M / G ratio from the viewpoint of the storage stability (appearance, pH, viscosity) of the preparation, the thickening effect by Ca ions, and the improvement in the oral retention of medicinal components. The thing of 0.5-2.0 is used. Preferably, the M / G ratio is 0.6 to 1.7, more preferably the M / G ratio is 0.7 to 1.5. When the M / G ratio exceeds 2.0, the storage stability (appearance, viscosity) and the thickening effect due to Ca ions are low, and further, the sufficient improvement effect in the oral retention of the medicinal component is not exhibited. When the M / G ratio is less than 0.5, the thickening effect due to Ca ions is high, but the liquid composition used in combination with sodium carboxymethylcellulose may cause partial gelation during storage, or on the appearance stability. May be a problem.

The M / G ratio of sodium alginate can be measured, for example, according to a known method (the method described in Carbohydrate Research, 32 (1974), 217-225).
Two types of uronic acids (M: mannuronic acid, G: guluronic acid) constituting alginic acid can be classified into three types of blocks based on their arrangement. They are a homopolymer (MM fraction) in which mannuronic acids are polymerized, a homopolymer (GG fraction) in which guluronic acids are polymerized, and a heteropolymer (MG fraction) in which mannuronic acid and guluronic acid are alternately polymerized. Since these blocks have different resistance to hydrolysis and solubility in pH, they were decomposed under the conditions that they were cleaved into, for example, the MM fraction, the GG fraction, and the MG fraction. Thereafter, each fraction is fractionated according to a conventional method, and then the sugar amount of each obtained fraction is measured by the phenol sulfuric acid method, and the M / G ratio can be calculated from the formula shown below.
M / G = (sugar amount of MM fraction + (sugar amount of MG fraction / 2)) / (sugar amount of GG fraction + (sugar amount of MG fraction / 2))

  As such alginate of the component (A), those having different viscosities and M / G ratios are available from Kibun Food Chemifa Co., Ltd., Kimika Co., Ltd. and the like. For example, the viscosity is 10 to 20 mPa · s, the M / G ratio is 0.7 to 0.9, the viscosity is 15 to 25 mPa · s, the M / G ratio is 0.7 to 0.9, and the viscosity is 40 to 50 mPa · s. The M / G ratio is 0.7 to 0.9, the viscosity is 70 to 100 mPa · s, the M / G ratio is 0.7 to 0.9, the viscosity is 10 to 30 mPa · s, and the M / G ratio is 1. Alginic acid having a viscosity of 20 to 50 mPa · s, an M / G ratio of 1.2 to 1.4, a viscosity of 50 to 80 mPa · s and an M / G ratio of 1.2 to 1.4 Sodium is available. Here, as what is generally marketed with the sodium alginate which satisfy | fills the viscosity and M / G ratio of this invention, the duck argin NSPLL, SL-20, FF-SL-10 made from Kibun Food Chemifa Corporation, ( There are Kimika Argin IL-2 and IL-6 manufactured by Kimika Co., Ltd.

  The blending amount of the alginate as the component (A) is 0.5 to 2 of the entire composition from the viewpoint of the appearance stability of the preparation and the thickening effect by Ca ions, and further the improvement effect in the oral retention of the medicinal component. 0.0 mass%, preferably 0.6-1.7 mass%, more preferably 0.7-1.4 mass%. When the blending amount is less than 0.5% by mass, the thickening effect by Ca ions of the liquid composition is not sufficiently exhibited, and further, the sufficient improvement effect in the oral retention of the medicinal component may not be exhibited. . In addition, when the blending amount exceeds 2.0% by mass, not only the above effects can be obtained satisfactorily, but also a problem in appearance stability such as precipitation of a water-soluble polymer occurs in a combined composition with sodium carboxymethylcellulose. Occurs.

  The component (B) carboxymethylcellulose sodium (hereinafter abbreviated as CMC) in the liquid oral composition of the present invention is the storage stability (appearance) of the liquid composition, the thickening effect by Ca ions, and the medicinal component. From the viewpoint of an improvement effect on the retention in the oral cavity, those having a degree of etherification of 0.8 to 1.6, preferably 0.9 to 1.5, more preferably 1.0 to 1.4 are used. . When the degree of etherification exceeds 1.6, the effect of increasing the viscosity by Ca ions is low, and further, the effect of improving the retention in the oral cavity of the medicinal component is not exhibited. When the degree of etherification is less than 0.8, appearance stability and viscosity stability during storage are low, which is a problem in quality.

  The CMC used in the present invention is 500 to 5 when measured with a Brookfield viscometer (BL viscometer, 25 ° C., rotor No. 3 or No. 4, rotor speed 60 rpm, after 60 seconds of rotation). It is preferable to use one having a viscosity of 000 mPa · s. If the viscosity is less than 500 mPa · s, it is difficult to give the composition a sufficient viscosity, and there is a problem in terms of usability in that an appropriate amount is discharged from the container or held on the interdental brush or finger. May occur. Moreover, when it exceeds 5,000 mPa · s, there may be a problem in terms of usability of discharging an appropriate amount from the container or usability such as stickiness in the oral cavity.

  Such CMCs having different etherification degrees and viscosities are commercially available from Daicel Chemical Industries, Ltd., Nippon Paper Chemicals Co., Ltd., etc. For example, CMC Daicel <1290> manufactured by Daicel Chemical Industries, Ltd. (Degree of etherification: 0.8 to 1.0, Viscosity: 1,000 to 2,000 mPa · s), CMC Daicel <1380> (Degree of etherification: 1.0 to 1.5, Viscosity: 1,000 to 2,000 mPa · s), CMC Daicel <1390> (degree of etherification: 1.0 to 1.5, viscosity: 2,500 to 4,500 mPa · s), CMC Daicel <2200> (degree of etherification: 0. 8 to 1.0, viscosity: 1,500 to 2,500 mPa · s), CMC Daicel <2450> (degree of etherification: 1.1 to 1.3, viscosity: 2,500 to 5,000 mPa · s) , Nippon Paper Industries Sunrose F300HC (degree of etherification: 0.85 to 0.95, viscosity: 2,500 to 3,500 mPa · s) manufactured by Cal Co., Ltd., Sunrose H-300H (degree of etherification: 0.8 to 1) 0.0, viscosity: 2,500 to 3,500 mPa · s).

  In the present invention, the blending amount of CMC as the component (B) is such that the appropriate amount is discharged from the container or held on the interdental brush or finger, the appearance stability of the preparation, and the increase by Ca ions. From the viewpoint of the effect of improving the viscosity effect and further the retention in the oral cavity of the medicinal component, it is 0.2 to 1.2% by mass of the whole composition, preferably 0.4 to 1.0% by mass, more preferably 0.5 to 0.8 mass%. When the blending amount is less than 0.2% by mass, since the viscosity of the preparation in which the low-viscosity alginate of the component (A) is used in the range of 0.5 to 2.0% by mass is extremely low, usability (discharge) When there is a problem in terms of properties and retention, and the thickening effect due to Ca ions is fully exerted, but because the viscosity is extremely low, it is immediately washed away in the oral environment where saliva is present There is. When the amount exceeds 1.2% by mass, a problem occurs in terms of usability of discharging an appropriate amount from the container, and the thickening effect due to Ca ions of the composition may be significantly impaired. In some cases, sufficient improvement in oral retention may not be exhibited. Moreover, when the compounding quantity of CMC exceeds 1.2 mass% with the liquid composition used together with an alginate, the problem on quality, such as precipitation of water-soluble polymer, may generate | occur | produce.

  Furthermore, the blending amount of (A) alginate and (B) CMC is the usability (dischargeability, retention), feeling of use, the appearance stability of the preparation, the thickening effect by Ca ions, and the oral cavity of the medicinal component. From the viewpoint of the effect of improving the retention, the mass ratio of component (A) / component (B) is 0.5 to 6.0, preferably 0.7 to 4.0, more preferably 0.9 to 2.5. It becomes the range which becomes. When the ratio (A) / (B) is less than 0.5, the feeling of use is poor, the thickening effect due to Ca ions is not sufficiently exhibited, and further, the sufficient improvement effect in the oral retention of the medicinal component is not exhibited. . If it exceeds 6.0, a serious problem in appearance stability such as precipitation of a water-soluble polymer occurs, the effect of thickening due to Ca ions is not sufficiently exhibited, and further, the oral cavity of the medicinal component There may be a case where a sufficient improvement effect in the internal retention is not exhibited. Moreover, in the formulation which used together the low-viscosity alginate in the range of 0.5-2.0 mass%, a malfunction may arise in terms of usability (discharge property, retainability).

The component (C) in the liquid oral composition of the present invention is represented by the following general formula (1).
_{M n H 3-n PO 4} (1)
(However, M represents Na or K, and n is 1, 2 or 3.)
It is a phosphate represented by.

  Specific examples of the phosphate of formula (1) include sodium monohydrogen phosphate, potassium monohydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, and the like. You may mix | blend individually or in combination of 2 or more types. Of these, sodium monohydrogen phosphate, sodium dihydrogen phosphate, and trisodium phosphate are particularly preferably used.

  In the present invention, the blending amount of the phosphate of formula (1) is the storage stability (appearance, pH, viscosity) of the preparation, the thickening effect by Ca ions, and the improvement effect on the oral retention of the medicinal component. From 0.05 to 0.5 mass% of the whole composition, preferably from 0.07 to 0.4 mass%, more preferably from 0.09 to 0.2 mass%. If the blending amount is less than 0.05% by mass, the pH stability is low, and as a result, the viscosity of the composition is remarkably lowered or the viscosity is not expressed in the preparation using a combination of alginate and CMC. There may be a problem in quality due to problems in terms of (dischargeability, retention), or water-soluble polymers insolubilized and deposited during storage. If it exceeds 0.5% by mass, the composition will be significantly discolored under high temperature storage, causing problems in appearance stability, and the thickening effect by Ca ions of the composition will be significantly impaired. Furthermore, there may be a case where a sufficient improvement effect is not exhibited in the oral cavity retention of the medicinal component.

  The (D) moisture content in the liquid oral composition of the present invention is 45% of the total composition from the viewpoint of the appearance stability of the preparation, the thickening effect by Ca ions, and the improvement effect of the medicinal component in the oral cavity retention. It is -90 mass%, Preferably it is 50-80 mass%, More preferably, it is 55-75 mass%. If the water content is less than 45% by mass, quality problems such as precipitation of water-soluble polymers occur during storage, the thickening effect due to Ca ions of the composition may not be sufficiently exhibited, A sufficient improvement effect may not be exhibited in the retention of the medicinal component in the oral cavity. If it exceeds 90% by mass, there may be a problem in appearance stability or a problem in quality.

  The pH after 3 minutes at 25 ° C. of the liquid oral composition of the present invention is in the range of 6.0 to 8.5 from the viewpoint of the storage stability (appearance, pH, viscosity) of the preparation, preferably 6. It is in the range of 3 to 8.0, more preferably 6.6 to 7.7. When the pH is less than 6.0, the viscosity stability of the composition is remarkably lowered, which causes a serious problem in quality. Further, when the pH is less than 5.5, the possibility that the teeth are decalcified is not preferable. If it exceeds 8.5, discoloration of the composition becomes remarkable, resulting in problems in appearance stability. In addition, a composition containing a fragrance component is not preferable because it may cause quality problems such as significant deterioration of flavor and may cause damage to the oral mucosa.

  Here, as a means for adjusting the pH to the range of 6.0 to 8.5, the phosphate of the above formula (1) is used alone or in combination of two or more thereof, and is blended within the above blending amount range. In addition to the method of adjusting and the phosphate of the above formula (1), other pH adjusting agents such as phosphoric acid, hydrochloric acid, sodium hydroxide, sodium carbonate, sodium hydrogen carbonate and the like are also used. In particular, a combined system of sodium monohydrogen phosphate and sodium dihydrogen phosphate, a combined system of sodium monohydrogen phosphate or trisodium phosphate and hydrochloric acid, a combined system of sodium dihydrogen phosphate and sodium hydroxide or sodium bicarbonate In particular, a combined system of sodium monohydrogen phosphate and sodium dihydrogen phosphate, sodium dihydrogen phosphate and sodium hydrogen carbonate is more preferable.

In the composition for liquid oral cavity of the present invention, particularly when the amount of CMC is 0.2 to 0.8% by mass, it is preferable to further add (E) xanthan gum. (Retention property) and storage stability (appearance, viscosity) of the preparation can be further improved. Xanthan gum is a polysaccharide obtained by fermenting hydrocarbons with Xanthomonas campestris, and is mainly composed of sodium, potassium and calcium salts of D-glucose, D-mannose and D-glucuronic acid. It is marketed by the company under the trade names such as Echo Gum, Monato Gum, Keldent, Celtolol. Among these, monate gum DA, keldent, echo gum T, and celtrol T are preferably used, and monate gum DA and keldent are more preferably used.
The xanthan gum used in the present invention was measured for viscosity (Brookfield viscometer, 25 ° C., rotor No. 3, rotation speed 60 rpm, after 30 seconds of rotation) by the method defined in the section of Pharmaceutical Additive Standard 2003 “Xanthan Gum”. What is sometimes 600 to 2,000 mPa · s is suitable. If it is less than 600 mPa · s, it may be difficult to give the composition a sufficient viscosity, and there is a problem in terms of usability in that an appropriate amount is discharged from the container or held on the interdental brush or finger. May occur. Moreover, when it exceeds 2,000 mPa · s, there may be a problem in terms of usability of discharging an appropriate amount from the container or usability such as stickiness in the oral cavity.

When blending the xanthan gum of component (E), the blending amount is such that the appropriate amount is discharged from the container or held on the interdental brush or finger, the appearance stability of the formulation and the increase by Ca ions. From the viewpoint of the viscosity effect and the effect of improving the retention of the medicinal component in the oral cavity, 0.1 to 0.4% by mass, particularly 0.1 to 0.3% by mass of the whole composition is preferable.
Furthermore, when xanthan gum is blended, the total blending amount of CMC of component (B) and xanthan gum of component (E) is increased by use (retention), storage stability (appearance, viscosity) and Ca ion. It is preferable to mix in the range of 0.3 to 1.2% by mass of the whole composition from the viewpoint of the sticking effect and the effect of improving the retention of the medicinal component in the oral cavity, particularly 0.5 to 1.0%. It is more preferable to become mass%.

  The composition of the present invention can further contain (F) a fluorine compound, (G) an anti-inflammatory agent, and (H) a fungicide. In this invention, the mixing | blending of these medicinal components can exhibit the oral retention property which was excellent in the medicinal component. That is, the liquid oral composition of the present invention thickens by reaction with the oral saliva component, and the medicinal component stays in the oral cavity, so that the action of the medicinal component is continuously exhibited at the application site. Is possible.

  Furthermore, since the liquid oral composition of the present invention can improve the effectiveness due to the retention of the medicinal component, the amount of the medicinal component in the composition corresponding to the improvement in effectiveness is reduced. It becomes possible to do. As a result, not only can the cost of the contents be reduced, but also the amount of ingredients to be blended in order to stabilize the medicinal ingredients can be reduced, and the effect of improving the flavor (bitter taste etc.) derived from the raw material is exhibited. You can also

  Examples of (F) fluorine compounds include sodium fluoride and sodium monofluorophosphate, and sodium monofluorophosphate is particularly preferably used. It is important to set the compounding amount of the fluorine compound within the range of the appropriate compounding amount from the viewpoint of effectiveness and the thickening effect by Ca ions, and further the effect of improving the retention of medicinal components in the oral cavity. It is preferable to set it as 0.01-0.2 mass% with respect to the whole thing.

  When sodium fluoride is blended, the blending amount is preferably 0.01 to 0.2% by weight, more preferably 0.02 to 0.1% by weight, and 0.03 to 0.08, based on the entire composition. More preferred is mass%. If it is less than 0.01% by mass, it is not satisfactory in terms of effectiveness, and if it exceeds 0.2% by mass, the thickening effect due to Ca ions of the composition may not be sufficiently exhibited. In some cases, sufficient improvement in oral retention may not be exhibited.

  In the case of blending sodium monofluorophosphate, the blending amount is preferably 0.04 to 0.8% by weight, more preferably 0.07 to 0.4% by weight, based on the total composition, 0.25 mass% is still more preferable. If it is less than 0.04% by mass, it is not satisfactory in terms of effectiveness, and if it exceeds 0.8% by mass, the thickening effect due to Ca ions of the composition may not be sufficiently exhibited. In some cases, sufficient improvement in oral retention may not be exhibited.

  In the liquid composition of the present invention, the viscosity stability can be further improved by blending (F) a fluorine compound.

  (G) As an anti-inflammatory agent, any of water-soluble or poorly water-soluble anti-inflammatory agents can be blended. (G-1) As a water-soluble anti-inflammatory agent, tranexamic acid, epsilon aminocaproic acid, dipotassium glycyrrhizinate, etc. (G-2) Examples of the poorly water-soluble anti-inflammatory agent include glycyrrhetinic acid, dl-α-tocophenol acetate (vitamin E), and the like. As the anti-inflammatory agent, it is particularly preferable to use tranexamic acid, epsilon aminocaproic acid, dipotassium glycyrrhizinate, and glycyrrhetinic acid, and it is more preferable to use dipotassium glycyrrhizinate and glycyrrhetinic acid.

  (G) When mix | blending an anti-inflammatory agent, the compounding quantity has 0.005-1.0 mass% of the whole composition good, 0.01-0.5 mass% is more preferable, 0.02-0 More preferably, 2% by mass.

  Examples of (H) fungicides include isopropylmethylphenol, triclosan, hinokitiol, cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, chlorhexidine gluconate, chlorhexidine hydrochloride, and the like. Among them, isopropylmethylphenol, triclosan, cetylpyridinium chloride, Benzethonium chloride and benzalkonium chloride are preferably used, and isopropylmethylphenol, triclosan, and cetylpyridinium chloride are particularly preferably used.

  (H) When mix | blending a disinfectant, the compounding quantity has 0.005-0.5 mass% of the whole composition good, 0.01-0.3 mass% is more preferable, 0.02-0. 1% by mass is more preferable.

  In the composition of the present invention, (F) a fluorine compound selected from sodium fluoride and sodium monofluorophosphate, (G-1) a water-soluble anti-inflammatory agent selected from tranexamic acid, epsilon aminocaproic acid and glycyrrhizinate In the composition containing either component or both components, the effect of the present invention is exhibited even if a nonionic surfactant and / or ethanol is not blended.

  On the other hand, (G-2) glycyrrhetinic acid, dl-α-tocophenol acetate (vitamin E), a poorly water-soluble anti-inflammatory agent, (H) isopropylmethylphenol, triclosan, hinokitiol, cetylpyridinium chloride, benzethonium chloride, When blending either or both components of a bactericide selected from benzalkonium, chlorhexidine gluconate, and chlorhexidine hydrochloride, (I) nonionic surfactant and / or (J) ethanol may be blended desirable. Solubilizing poorly water-soluble anti-inflammatory agents such as glycyrrhetinic acid, and solubilizing water-insoluble fungicides such as isopropylmethylphenol and triclosan in the formulation, preventing adsorption to container materials such as container stoppers, or cetylpyridinium chloride And the like can be prevented from becoming cloudy in a preparation containing alginate and xanthan gum.

  As the nonionic surfactant (I), various conventionally known surfactants can be used. For example, polyoxyethylene fatty acid ester such as polyoxyethylene hydrogenated castor oil, sucrose fatty acid ester such as sucrose fatty acid ester, maltose fatty acid ester, sugar alcohol fatty acid ester such as maltitol fatty acid ester, lactol fatty acid ester, alkylol amide, Polyoxyethylene sorbitan monostearate and other polyoxyethylene sorbitan fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyoxyethylene glycol fatty acid esters, polyethylene glycol fatty acid esters, polyoxy Fatty acid diethanolamine such as ethylene polyoxypropylene glycol, lauric acid mono- or diethanolamide , Polyoxyethylene alkyl ethers, polyoxyethylene alkyl phenyl ether, and the like.

  As nonionic surfactants, in particular, poorly water-soluble anti-inflammatory agents, bactericides, and perfume ingredients are solubilized, resulting in the retention effect of medicinal ingredients and storage stability (appearance stability) The average addition mole number of ethylene oxide is 30 to 300 and the average addition mole number of propylene oxide is 30 to 70. It is preferable to use polyoxyethylene hydrogenated castor oil having an alkyl group of 40 to 120, polyoxyethylene alkyl ether having an alkyl group with a carbon chain length of 16 to 18 and an average added mole number of ethylene oxide of 10 to 50, especially ethylene oxide. The average number of moles added was 200 and the average number of moles added of propylene oxide was 7 Polyoxyethylene polyoxypropylene glycol, polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 60 to 100, an alkyl group having a carbon chain length of 16 to 18 and an average addition mole number of ethylene oxide of 20 to 20 More preferably, 50 polyoxyethylene alkyl ethers are used. Polyoxyethylene polyoxypropylene glycol is commercially available from BASF, etc., and polyoxyethylene hydrogenated castor oil is commercially available from Nikko Chemicals Co., Ltd., Nippon Emulsion Co., Ltd. and the like. Polyoxyethylene alkyl ether is commercially available from Nippon Emulsion Co., Ltd., Lion Chemical Co., Ltd.

In addition, when mix | blending a nonionic surfactant, the compounding quantity is 0.1-5.0 mass% of the whole composition normally, especially 0.2 to such an extent that the effect of a liquid oral composition is not impaired. It is preferable that it is -4.0 mass%. For example, when polyoxyethylene polyoxypropylene glycol having an average addition mole number of ethylene oxide of 200 and an average addition mole number of propylene oxide of 70 is used, it is preferably blended in an amount of 0.2 to 2.0 mass%. When polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 60 is used, it is preferably blended in an amount of 0.1 to 1.5% by mass. When polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 100 is used, it is preferable to blend 0.3 to 4.0% by mass. When a polyoxyethylene alkyl ether having an alkyl group having a carbon chain length of 16 to 18 and an average added mole number of ethylene oxide of 20 to 50 is used, it is preferably blended in an amount of 0.2 to 2.0% by mass.
When the blending amount of the nonionic surfactant is less than 0.1% by mass, it may be difficult to maintain the appearance stability, and when it exceeds 5.0% by mass, the action of the bactericide and / or the anti-inflammatory agent is caused. It may be hindered, taste bad, and the feeling of use may be significantly impaired.

  (J) As for the compounding quantity of ethanol of a component, 0-15 mass% of the whole composition is preferable normally, More preferably, it is 2-12 mass%, Most preferably, it is 3-8 mass%. If it exceeds 15% by mass, water-soluble polymers such as alginate and CMC may become insoluble or problems in appearance and property stability may occur. Moreover, irritation | stimulation is strong and a usability | use_condition may be impaired remarkably. Note that the blending amount of ethanol includes a small amount of ethanol in the blended fragrance.

  The liquid oral composition of the present invention can be applied to a liquid product such as a normal toothpaste, a liquid product such as an interdental brush or dental floss, and a sheet such as a finger or a non-woven fabric. Application agent applied to cervical and gingiva, etc., type of application product to be administered directly to interproximal part, periodontal pocket, etc. in a container equipped with a fine-pointed nozzle, diluted with water before use Can be applied to products such as concentrated mouthwashes and gargles, etc., but it is especially a liquid product for interdental areas applied by an interdental brush, a product for cervical or gingival application applied by fingers It is effective as

  When preparing the composition of the present invention into the above-mentioned various dosage forms, various components that are usually used in oral compositions can be blended. Since the blending amounts are different, it is necessary to select the components and blending amounts in the same manner as in the past and to the extent that the effects of the present invention are not hindered.

  For example, in the case of liquid dentifrice, abrasives, wetting agents, viscosity modifiers, surfactants, sweeteners, preservatives, fragrances, colorants, pH adjusters, active ingredients, cleaning aids, etc. are mixed with water. And can be produced according to a conventional method.

  As abrasives, silica-based abrasives such as precipitated silica, silica gel, aluminosilicate, zirconosilicate, dicalcium phosphate (dihydrate or anhydride), primary calcium phosphate, tricalcium phosphate, calcium pyrophosphate, calcium carbonate , Aluminum hydroxide, alumina, magnesium carbonate, tribasic magnesium phosphate, insoluble sodium metaphosphate, insoluble potassium metaphosphate, titanium oxide, zeolite, anhydrous silicic acid, hydrous silicic acid, titanium silicate, zirconium silicate, synthetic resin system An abrasive | polishing agent etc. are mentioned, It is preferable to use a silica type abrasive | polishing agent especially. The compounding quantity is 0-30 mass% normally with respect to the whole composition.

  Examples of the wetting agent include propylene glycol, glycerin, sorbitol, xylitol, maltitol, lactol, erythritol, palatinose, trehalose, polyhydric alcohols such as polyethylene glycol having an average molecular weight of 190 to 9,300, 1,3-butylene glycol, sugar Alcohol etc. are mentioned. Among these, it is preferable to use propylene glycol, sorbit, or glycerin. The total amount of the wetting agent is usually 5 to 40% by mass, preferably 8 to 35% by mass, and more preferably 10 to 30% by mass of the entire composition. If the amount is less than 5% by mass, the feeling in use in the oral cavity is deteriorated. If the amount exceeds 40% by mass, the thickening effect by Ca ions of the composition may be significantly impaired. In some cases, the improvement effect on the property is not sufficiently exhibited.

In the present invention, in addition to the above (I) nonionic surfactant, other surfactants are blended so as not to impair the effects of the present invention of the liquid oral composition in order to solubilize the poorly water-soluble fragrance component. You can also Specifically, alkyl sulfates, N-acyl sarcosine acids, sodium dodecylbenzenesulfonates, hydrogenated coconut fatty acid sodium monoglyceride monosulfate, sodium lauryl sulfoacetate, N-acyl glutamates such as sodium N-palmitoyl glutamate, N- Anionic surfactants such as sodium methyl-N-acyl taurate, sodium N-methyl-N-acylalanine, sodium α-olefin sulfonate, cationic surfactants such as alkyl ammonium and alkyl benzyl ammonium salts, betaine acetate, Examples include amphoteric surfactants such as imidazolinium betaine. The blending amount is usually preferably 0 to 3% by mass, particularly preferably 0 to 2% by mass, based on the entire composition. If it exceeds 3% by mass, the oral mucosa may be irritated.
In this case, it is preferable that the total compounding amount with said (I) nonionic surfactant is 0.1-5.0 mass% of the whole composition.

  Examples of sweeteners include saccharin sodium, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidyl hydrochalcone, perlartin, glycyrrhizin, thaumatin, asparatylphenylalanine methyl ester, and the like.

  As perfumes, spearmint oil, peppermint oil, anise oil, eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil, lime Natural fragrances such as oil, lavender oil, rosemary oil, laurel oil, camomil oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, cinnamon bark oil, menthol, menton, carvone , Ethyl butyrate, vanillin, ethyl maltol, anethole, methyl salicylate, synamic aldehyde, thymol, cineol, eugenol, ethyl vanillin, maltol, limonene, citronellol, linalool, linalyl acetate, menthyl acetate, Single item fragrances such as nene, octylaldehyde, citral, pulegone, calbe acetate, anisaldehyde, ginger oleoresin, creosole, dl-camphor, further ethyl acetate, allyl cyclohexane propionate, methyl anthranilate, ethyl methyl phenyl It is possible to use known fragrances used in oral compositions such as singular fragrances such as glycidate, undecalactone, hexanal, ethyl alcohol, propyl alcohol, butanol, isoamyl alcohol and / or various blended fragrances including natural fragrances. It is possible and it is not limited to the fragrance | flavor of an Example. Moreover, although a compounding quantity is not specifically limited, It is preferable to mix | blend 0.01-1 mass% of one fragrance | flavor raw material in a composition like many known examples.

  In the case of a liquid composition for interdental area applied by an interdental brush, or for a cervical part or gingiva applied by a finger, it satisfies the actual feeling of use such as a refreshing feeling and a refreshing feeling at the application site. In particular, it is preferable to blend a fragrance component selected from mint oil, spearmint oil, peppermint oil, clove oil, menthol, menthone, anethole, eugenol, thymol, cineol, and dl-camphor as a fragrance. The blending amount of these fragrance components is usually preferably from 0.1 to 0.8% by mass, more preferably from 0.2 to 0.7% by mass, and particularly preferably from 0.3 to 0.6% by mass of the entire composition. preferable. If it is less than 0.1% by mass, the refreshing feeling and refreshing feeling at the application site are insufficient, so that it is not satisfactory in terms of actual use, and if it exceeds 0.8% by mass, the irritation at the application site is not achieved. The feeling is strong and the feeling of use may be worsened.

  As colorants, Red No. 2, Red No. 3, Red No. 225, Red No. 226, Yellow No. 4, Yellow No. 5, Yellow No. 205, Blue No. 1, Blue No. 2, Blue No. 201, Blue No. 204, Green No. 3 etc. Legal dye, caramel dye, safflower dye, gardenia dye, cochineal dye, anato dye, mica titanium, titanium oxide and the like.

  As the preservative, benzoic acid and its salt, salicylic acid and its ester or salt, parabens, phenol and the like can be used as necessary in addition to the above (H) fungicide.

  Examples of active ingredients include ascorbic acid and salts thereof, allantoin and derivatives thereof, glycyrrhizic acid, tocopherols other than dl-α-tocophenol acetate, pyridoxine hydrochloride (vitamin B6), sodium azulenesulfonate, diclofenac sodium, indomethacin, acemetacin , Sulindac, ibuprofen, flurbuprofen, pranoprofen, ketoprofen, phenacetin, acetaminophen, mefenamic acid, tetrahydrozoline hydrochloride, aminoethylsulfonic acid (taurine), hydrocortisone acetate, diphenhydramine salicylate, miconazole, ethyl aminobenzoate, Plants such as Abou, Oren, Ogon, Hamamelis, Clove, Chamomile, Latania, Myrrh, Touki, Rosemary, Safflower Extracts, dextranase, mutanase, lysozyme chloride, amylase, protease, lytic enzyme, superoxide dismutase and other enzymes, augmentin, amoxicillin, tetracycline, doxycycline, minocycline hydrochloride, metronidazole, neomycin, kanamycin, clindamycin and other antibiotics , Sodium chloride, potassium nitrate, carbonate, bicarbonate, sesquicarbonate, etc., α-bisabolol, methoxyethylene maleic anhydride copolymer, epidihydrocholesterin, dihydrocholesterol, epidihydrocholesterin, trichlorocarbanilide , Alanine, glycine, proline, L-arginine, sodium L-aspartate, trimethylglycine, alkyldiaminoethylglycine hydrochloride, decalinium chloride It may be formulated lauroyl sarcosine sodium and the like alone or in combination. The amount of the active ingredient added can be an effective amount as long as the effects of the present invention are not hindered.

  In the liquid oral composition of the present invention, the composition containing a water-soluble divalent metal salt such as calcium or magnesium may gel during storage or may cause significant discoloration. From the viewpoint of stability of properties, water-soluble divalent metal salts such as calcium and magnesium are not blended or contained in an extremely small amount (specifically, contained in an amount of about 0 to 0.1% by weight based on the entire composition) Amount). Polyphosphates and pyrophosphates are preferably not blended because the thickening effect due to Ca ions is significantly impaired.

Furthermore, the viscosity at 25 ° C. of the liquid oral cavity composition of the present invention is such that the appropriate amount is discharged from the container or held on the interdental brush or finger, and the thickening effect by Ca ions, In the case of measuring using a Brookfield viscometer (BL type viscometer, rotor No.1 to No.3, rotation speed 12 rpm, 2 minutes after rotation) from the viewpoint of improving the retention of medicinal components in the oral cavity , 600 Ri 3,400 mPa · s der, more preferably 800~3,000mPa · s. The viscosity is less than 400 mPa · s of the composition, usability (ejection property, retention) trouble arising in terms of. Exceeds 8,000 mPa · s, or cause troubles in terms of usability (dischargeability), thickening effect is not such be sufficiently exhibited by Ca ions of the composition. Furthermore, sufficient improvement is not such to exhibit the retention of the medicinal ingredient. Also, poor dispersibility of the formulation when applied to the oral cavity, that a poor feeling.

  Moreover, there is no restriction | limiting in particular as a container which accommodates the liquid oral cavity composition of this invention, Usually, the container currently applied to the oral cavity composition can be filled and used. Specifically as such a container, a polyethylene layer, an ethylene methacrylic acid copolymer layer, a polyethylene terephthalate layer, an aluminum layer, a glass vapor deposition layer, a polyvinyl alcohol layer, an ethylene vinyl alcohol copolymer layer, an acrylonitrile copolymer layer, Laminate containers made of paper, recycled plastic layers, etc., or polyethylene containers, polyethylene terephthalate containers, polypropylene containers, etc. can be used. Tube containers, dispensers containers with mechanical or differential pressure, film packaging containers such as pillow packaging, etc. Various containers usually used as the composition can be used.

Below, usability, storage stability, thickening effect due to Ca ions, and medicinal components using composition examples (Examples) and non-applicable composition examples (comparative examples) corresponding to the liquid oral composition of the present invention The effect of improving the retention will be shown, and the characteristics and excellent effects of the present invention will be specifically described. However, the present invention is not limited to these examples.
In addition, the viscosity and M / G ratio of sodium alginate were measured by the following method.

(I) Measurement of viscosity of sodium alginate The viscosity of sodium alginate was measured according to a known method using a Brookfield viscometer. The sample preparation method is as follows.
Into a 300 mL beaker, 198 mL of purified water was poured, and 2.00 g of sodium alginate raw material was added little by little while stirring vigorously with a magnetic stirrer. After stirring for 30 minutes (If not dissolved in 30 minutes, continue stirring until dissolved. If there is a large mamako, crush it with a bamboo spatula etc.) Was removed from the stirrer, and an appropriate amount of the solution was transferred to a tall beaker for viscosity measurement (φ4.2 cm). While measuring the liquid temperature with a rod-shaped thermometer, the liquid temperature was adjusted to about 20 ° C. by attaching it to ice water or hot water. At this time, it was adjusted while stirring well so that the liquid temperature would not become uneven. When the liquid temperature reached about 20 ° C., it was allowed to stand for 20 to 40 minutes in a constant temperature water bath set at about 20 ° C. After 20 to 40 minutes, the solution in the beaker was lightly stirred to confirm that the liquid temperature was 20 ° C., and the viscosity was measured using a BM viscometer (manufactured by Toki Sangyo Co., Ltd.). Viscosity (mPa · s) was calculated by setting the number of revolutions to 30 rpm and the reading value after 60 seconds as a measured value. The rotor used was changed according to the viscosity range shown below.
(Rotation speed: 30rpm)
Rotor No. 1: Viscosity range from 2 to 160 mPa · s. 2: Range exceeding 160 to 1,000 mPa · s

(II) Measurement of M / G ratio of sodium alginate The M / G ratio of sodium alginate was measured according to a known method (the method described in Carbohydrate Research, 32 (1974), 217-225).
That is, the two types of uronic acids (M: mannuronic acid, G: guluronic acid) that make up alginic acid can be classified into three types of blocks based on how they are arranged. They are a homopolymer (MM fraction) in which mannuronic acids are polymerized, a homopolymer (GG fraction) in which guluronic acids are polymerized, and a heteropolymer (MG fraction) in which mannuronic acid and guluronic acid are alternately polymerized. Since these blocks have different resistance to hydrolysis and solubility in pH, they are decomposed into MM fraction, GG fraction, and MG fraction using the properties, and then each fraction is subjected to a conventional method. Fractionation (see experimental flow chart shown in FIG. 1). Next, the amount of sugar in each of the obtained fractions was measured by the phenol sulfuric acid method, and the M / G ratio was calculated from the formula shown below.
M / G = (sugar amount of MM fraction + (sugar amount of MG fraction / 2)) / (sugar amount of GG fraction + (sugar amount of MG fraction / 2))

Moreover, the test liquid composition was prepared by the following method.
Preparation of test liquid composition:
It was prepared with a vacuum emulsification kettle according to the following method.
First, ion-exchanged water is added, pH adjusters (phosphates, etc.), water-soluble medicinal ingredients (sodium monofluorophosphate, cetylpyridinium chloride, dipotassium glycyrrhizinate, etc.), pigments, preservatives (sodium benzoate), etc. Were dissolved by mixing and stirring. Next, a wetting agent such as sorbite liquid and glycerin was blended, and then mixed and stirred. Next, alginate and / or CMC were blended in propylene glycol taken in another container, dispersed by stirring, and then gradually added to the aqueous solution, and sufficiently mixed and stirred to dissolve. Furthermore, poorly water-soluble components such as nonionic surfactants, alcohols, poorly water-soluble medicinal components (isopropylmethylphenol, glycyrrhetinic acid, etc.), and fragrances were blended with reference to the physical properties of the raw materials. All the ingredients were blended, and after mixing and stirring sufficiently, the preparation after dissolution was defined as a product immediately after production.

[Examples 1-6, Comparative Examples 1-16]
Test liquid compositions having the compositions shown in Tables 1 to 3 were prepared according to the method described above, and the usability (dischargeability, retention), pH, viscosity and Ca ion thickening effect of the product immediately after production were determined according to the method described below. evaluated. Furthermore, after filling the preparation into a transparent container (250 mL) made of PET, each stored product was stored in a thermostatic bath at -5 ° C. and 50 ° C. for 1 month and left at room temperature for 1 day according to the method shown below. Storage stability (appearance, pH, viscosity) was evaluated. The results are shown in Tables 1-3.

  In addition, as the alginate, sodium alginate having different viscosity and M / G ratio manufactured by Kibun Food Chemifa Co., Ltd. or Kimika Co., Ltd. was used. In addition, CMCs having different degrees of etherification (both viscosities are 1,600 mPa · s) manufactured by Daicel Chemical Industries, Ltd. were used. As the phosphate, sodium monohydrogen phosphate and sodium dihydrogen phosphate were both manufactured by Taihei Chemical Industry Co., Ltd.

(1) Usability (dischargeability, holdability) evaluation of liquid composition for interdental brush (a) Dischargeability (criteria)
○: An appropriate amount of the preparation can be put out on the interdental brush by applying an appropriate force.
X: An excessive amount of the preparation appears on the interdental brush only by applying an appropriate force, or an appropriate amount of the preparation cannot be output on the interdental brush only by applying an appropriate force.
(B) Retention (Criteria)
○: An appropriate amount of the preparation is put on the interdental brush, and the preparation does not sag from the interdental brush until the interdental portion is brushed.
×: Appropriate amount of the preparation was put out on the interdental brush, and the preparation dropped from the interdental brush before the interdental portion was brushed.

(2) pH
About the sample moved to the glass container, the value after 3 minutes at 25 ° C. was measured with a pH meter (manufactured by Toa Denpa Kogyo Co., Ltd., HM-30V) and a pH electrode (manufactured by Toa Denpa Kogyo Co., Ltd., GST-5421C). It was measured.
(Criteria)
○: When the pH of the product immediately after production and the product stored at 50 ° C. are in the range of 5.5 to 8.5, and the change in pH due to storage is in the range of 0 to 0.5.
Δ: When the pH of the product immediately after production and the product stored at 50 ° C. are in the range of 5.5 to 8.5, and the pH change due to storage is in the range of more than 0.5 to 1.0.
X: When the pH of either the product immediately after production or the product stored at 50 ° C. is outside the range of 5.5 to 8.5, or when the pH change due to storage exceeds 1.0.

(3) Viscosity The sample was transferred to a glass screw tube (100 mL, Marum No. 8), sealed with a cap, and then left in a 25 ° C. water bath for 30 minutes. A BL type viscometer (manufactured by Toki Sangyo Co., Ltd.) was used, the rotation speed was 12 rpm, and the viscosity (mPa · s) was calculated from the reading value after 2 minutes. The rotor used was changed according to the viscosity range shown below.
(Rotation speed: 12rpm)
Rotor No. 1: Range of viscosity from 5 to 400 mPa · s. 2: Range in which the viscosity exceeds 400 and reaches 2,000 mPa · s. 3: Range of viscosity exceeding 2,000 to 10,000 mPa · s (judgment criteria)
A: When the rate of change in the viscosity of the product stored at 50 ° C. with respect to the viscosity of the product immediately after production is in the range of 0 to 10%.
○: When the rate of change in the viscosity of the product stored at 50 ° C. with respect to the viscosity of the product immediately after production exceeds 10% to 20%.
Δ: When the rate of change in viscosity of the product stored at 50 ° C. with respect to the viscosity of the product immediately after production is in the range of more than 20% to 30%.
X: When the change rate of the viscosity of the 50 degreeC storage goods with respect to the viscosity of the goods immediately after manufacture exceeds 30%.

(4) Appearance stability Regarding the preserved products, the appearance changes (precipitation of insoluble matter, gelation, two-phase separation, discoloration) of the preparation with respect to the products immediately after production were observed and evaluated according to the following criteria.
(Criteria)
○: Almost no change was observed in all of insoluble matter precipitation, gelation, two-phase separation and discoloration.
Δ: A slight change was observed in one or more terms of insoluble precipitation, gelation, two-phase separation and discoloration.
X: A remarkable change was observed in one or more of precipitation, gelation, two-phase separation and discoloration of insoluble matter.

(5) Thickening effect by Ca ions 80 g of the sample was transferred to a glass beaker (100 mL), and 20 g of a 25.5 mol / L calcium chloride aqueous solution was gradually added with stirring. The beaker after addition of the aqueous calcium chloride solution was left in a 25 ° C. water bath for 30 minutes, and then the viscosity (A1) was measured using a BL type viscometer. Separately, the viscosity (A2) when 20 g of ion-exchanged water was added instead of the calcium chloride aqueous solution was measured in the same manner, and the rate of increase in viscosity (times) was obtained from the following equation as an index of the thickening effect by Ca ions. .
Viscosity increase rate (times) = A1 / A2

The thickening effect by Ca ions was evaluated according to the following criteria. The viscosity of the sample after addition of the aqueous calcium chloride solution was 6 rpm, the viscosity after addition of ion-exchanged water was 12 rpm, and the rotor used was changed according to the viscosity range shown below.
(Rotation speed: 6rpm)
Rotor No. 1: Range of viscosity from 10 to 800 mPa · s. 2: Range in which the viscosity exceeds 800 and reaches 4,000 mPa · s. 3: Range in which the viscosity exceeds 4,000 to 16,000 mPa · s. 4: Viscosity ranges from over 16,000 to 100,000 mPa · s (rotation speed: 12 rpm)
Rotor No. 1: Range of viscosity from 5 to 400 mPa · s. 2: Range in which the viscosity exceeds 400 and reaches 2,000 mPa · s. 3: Range of viscosity exceeding 2,000 to 10,000 mPa · s (judgment criteria)
◎: Viscosity increase rate is 15 times or more ○: Viscosity increase rate is 7 times or more and less than 15 times △: Viscosity increase rate is 2 times or more and less than 7 times ×: Viscosity increase rate is less than 2 times

As is apparent from the results shown in Table 1, (A) an alginate having a viscosity of 5 to 100 mPa · s of a 1.0 mass% aqueous solution and an M / G ratio of 0.5 to 2.0 by mass ratio is obtained. 0.5 to 2.0% by mass, (B) 0.2 to 1.2% by mass of sodium carboxymethylcellulose having a degree of etherification of 0.8 to 1.6, (C) the following general formula (1)
_{M n H 3-n PO 4} (1)
(However, M represents Na or K, and n is 1, 2 or 3.)
0.05 to 0.5% by mass of the phosphate represented by formula (D), 45 to 90% by mass of water, and the mass ratio of (A) / (B) is 0.5 to 6%. The liquid oral composition (Examples 1 to 6) having a pH in the range of 0.0 and a pH at 25 ° C. in the range of 6.0 to 8.5 is excellent in usability (dischargeability, retention) and storage stability. Excellent effects were exhibited in any of the properties (appearance change, pH, viscosity) and the thickening effect by Ca ions. On the other hand, as is apparent from the results shown in Tables 2 and 3, in Comparative Examples 1 to 16 that do not satisfy any of the essential requirements of the present invention, usability (dischargeability, retention), storage stability (appearance) Change, pH, viscosity) and a thickening effect due to Ca ions were not satisfactory.

[Examples 7 to 16]
A test liquid oral composition for interdental brush or cervical application having the composition shown in Table 4 was prepared in the same manner as described above, and the usability (dischargeability, retention) in the same manner as in the above examples, Storage stability (appearance, pH, viscosity) and thickening effect by Ca ions were evaluated. Moreover, according to the method shown below, the improvement effect in the retention of the medicinal component of each composition was evaluated.
In addition, the usability of the liquid composition for application to the cervix is that the liquid composition (formulation) has a capacity of 20 mL and a bottle container having a discharge port with a diameter of 1 mm (container material: polyethylene terephthalate, inner plug material: polyethylene) The dispensing property when dispensing an appropriate amount of the formulation from the container onto the finger and the retention property until the formulation was applied to the cervical region after the formulation was dispensed were evaluated according to the following criteria. The results are shown in Table 5.

The representative raw materials were from the following manufacturers. Moreover, the fragrance | flavor used either of the types AF shown in Table 6.
・ Sodium alginate; manufactured by Kibun Food Chemifa Co., Ltd. or manufactured by Kimika Co., Ltd. (those with different viscosities and M / G ratios)
・ CMC; manufactured by Daicel Chemical Industries, Ltd. (with different degrees of etherification) (both viscosities are 1,600 mPa · s)
・ Sodium monohydrogen phosphate and sodium dihydrogen phosphate; manufactured by Taihei Chemical Industry Co., Ltd. ・ Polyoxyethylene hydrogenated castor oil (EO average addition mole number 60); Nikko Chemicals Co., Ltd.
Made (Product name: HCO-60)
・ Polyoxyethylene hydrogenated castor oil (EO average added mole number 100); Japan Emulsion (
(Product name: EMALEX HC-100)
・ Polyoxyethylene cetyl ether (EO average addition mole number 20); Japanese emulsion (
(Product name: EMALEX 120)
Polyoxyethylene polyoxypropylene glycol (EO average addition mole number 200, PO average addition mole number 70); manufactured by BASF (trade name: Lutrol F-127)
・ Ethanol: Nippon Alcohol Sales Co., Ltd. ・ Sodium monofluorophosphate; Rhodia Nikka Co., Ltd. ・ Sodium fluoride; Stella Chemifa Co., Ltd. ・ Cetylpyridinium chloride; Wako Pure Chemical Industries, Ltd. Methylphenol; Osaka Kasei Co., Ltd., glycyrrhetinic acid; Maruzen Pharmaceutical Co., Ltd., dipotassium glycyrrhizinate; Maruzen Pharmaceutical Co., Ltd.

(1) Usability (ejection and retention) evaluation of liquid composition for application to tooth neck (a) Ejection (determination criteria)
○: An appropriate amount of the preparation can be put out on the finger by applying an appropriate force.
X: Excessive formulation appears on the finger simply by applying moderate force. Or, it is not possible to produce an appropriate amount of the drug product simply by applying an appropriate force.
(B) Retention (Criteria)
○: An appropriate amount of the preparation is dispensed on the finger and the preparation does not sag from the finger until it is applied to the tooth neck.
X: An appropriate amount of the preparation is put out on the finger, and the preparation hangs down from the finger before it is applied to the tooth neck.

(2) Improving effect on retention of medicinal components (fluorine compound) 1 mL of artificial saliva having the composition shown below is added on a collagen-coated 6-well microplate (product number: IWAKI, Collagen Type I-Coated MICROPLATE 6 Well With Lid) After standing for a while, the upper layer solution was collected by a micropipette and discarded. Next, 0.5 g of an evaluation sample was collected on a collagen-coated plate and spread so as to be as uniform as possible. Next, 5 mL of ion exchange water (25 ° C.) was added onto the sample, and after standing for a while, the upper layer solution was recovered with a micropipette and discarded. Next, 1 mL of artificial saliva (37 ° C.) was added onto the sample, and after standing for 30 seconds, the upper layer solution was collected with a micropipette and discarded. This artificial saliva operation was performed once, and this cleaning operation was repeated 5 times, and the fluorine compound remaining in each plate was collected with an extraction solvent (ion-exchanged water). That is, 5 mL of ion exchange water was added and dispersed by pipetting, and then the entire amount of this solution was recovered. This extraction and recovery operation is repeated once more, each recovered solution is made up to 20 mL with ion-exchanged water, and the supernatant obtained by centrifugation (3,000 rpm, 10 minutes) is used as a medicinal component (fluorine compound). ) Was used as a sample solution for quantitative determination (S1). Moreover, the control sample at the time of performing the same operation with ion-exchange water (37 degreeC) instead of artificial saliva (37 degreeC) in the said operation was made into the sample solution (S2).

About each obtained sample solution (S1, S2), the fluorine ion concentration was measured in accordance with the method shown below.
15 mL of each sample solution was accurately weighed into a test tube with a stopper, and 5 mL of 1 mol / L sulfuric acid was accurately added and mixed, stoppered and heated for about 5 minutes. After cooling, 3 mL of this solution was accurately weighed, capped and heated for about 5 minutes. After cooling, 9 mL of acetate buffer solution (pH 5.3) was accurately added and mixed, and transferred to a plastic container to obtain a sample solution.
The same operation was performed using a fluorine standard solution for fluorine measurement (100 ppm) (manufactured by Thermo Orion) to prepare 2.5 ppm, 0.25 ppm, 0.05 ppm, and 0.0125 ppm fluorine standard solutions.
The sample solution and the fluorine standard solution were tested by the ion electrode method. A calibration curve was prepared by plotting the concentration of the fluorine standard solution on the logarithmic axis and the measured potential reading (mV) on the equiaxed axis. Next, the fluorine (F) concentration of the sample solution was calculated using a calibration curve prepared from the measured potential reading (mV) of the sample solution.

(3) Improving effect on retention of medicinal components (anti-inflammatory agent, bactericidal agent) Extracting medicinal components (anti-inflammatory agent, bactericidal agent) remaining in each plate after repeating washing operation 5 times according to the above method After recovering with a solvent (80% ethanol), the volume is made up to 20 mL, and each sample solution (S1, S2) obtained by centrifugation (3,000 rpm, 10 minutes) is filtered through a membrane filter and then shown below. According to the method, HPLC analysis was performed, and the concentration of the medicinal component in the sample was calculated from the relational expression between the peak area value and the concentration of a standard solution prepared separately. In addition, when quantitatively analyzing cetylpyridinium chloride, a mixture of 1 mL of the obtained sample solution and 1 mL of mobile phase was used as a sample.

In addition, it analyzed about three samples obtained by preparing on the same conditions. The average value of the obtained three data was calculated, and the retention improvement rate (%) of the medicinal component (fluorine compound, anti-inflammatory agent, bactericidal agent) was obtained from the following formula. Here, the improvement effect in the retention of medicinal components (fluorine compounds, anti-inflammatory agents, bactericides) was evaluated according to the following criteria.
Retention property improvement rate (%) = (medical component concentration of S1 / medical component concentration of S2) × 100
(Criteria)
◎: Retention property improvement rate is 250% or more ○: Retention property improvement rate is 175% or more and less than 250% △: Retention property improvement rate is 100% or more and less than 175% ×: Retention property improvement rate is less than 100%

  Here, the method for preparing artificial saliva is as follows. Add 950 mL of ion-exchanged water to a 1 L beaker, add calcium chloride, calcium chloride (dihydrate), potassium dihydrogen phosphate, magnesium chloride (hexahydrate) to the following concentrations and mix. Dissolved. Next, after adjusting pH to 7.0 with a 1 mol / L potassium hydroxide solution, ion exchange water was added to make the total volume 1L.

Artificial saliva composition:
Calcium chloride 50.0 mmol / L
Calcium chloride (dihydrate) 2.0 mmol / L
Potassium dihydrogen phosphate 1.0 mmol / L
Magnesium chloride (hexahydrate) 0.1 mmol / L
Potassium hydroxide appropriate amount (pH 7.0)
Ion exchange water remaining
Total 1L

(HPLC equipment)
Pump: JASCO Corporation (model number: PU-980)
Sample introduction part: manufactured by Kyowa Precision Co., Ltd. (model number: KSP-100X)
Detector: JASCO Corporation (model number: UV-970)
Recording device: manufactured by Stem Instruments Co., Ltd. (model number: Chromatocoder 21J
)
Column thermostat: manufactured by Senshu Scientific Co., Ltd. (model number: SSC-2100)

(1) HPLC analysis method for cetylpyridinium chloride Detector: Ultraviolet absorptiometer (measurement wavelength: 265 nm)
Column: Inertsil ODS-2 column (inner diameter 4 mm, length 150 mm)
(Manufactured by GL Sciences Inc.)
Column temperature: constant temperature around 30 ° C. Mobile phase: 750 mL of acetonitrile and phosphate buffer (sodium dihydrogen phosphate dihydrate;
7.8 g, phosphoric acid (3.4 mL) mixed with 250 mL, and further dissolved by adding 1.2 g of sodium lauryl sulfate and then filtered.
Flow rate: 1.0 mL / min
Sampling volume: 50 μL

(2) HPLC analysis method for isopropylmethylphenol Detector: Ultraviolet absorptiometer (measurement wavelength: 285 nm)
Column: YMC-Pack ODS-A A-303
(Inner diameter 4.6 mm, length 250 mm) (manufactured by YMC Co., Ltd.)
Column temperature: A constant temperature of around 45 ° C. Mobile phase: A mixture of 600 mL of acetonitrile, 400 mL of water and 10 mL of acetic acid, and filtered.
Flow rate: 0.8mL / min
Sampling volume: 50 μL

(3) HPLC analysis method of glycyrrhetinic acid Detector: UV absorption photometer (measurement wavelength: 250 nm)
Column: YMC-Pack ODS-A A-303
(Inner diameter 4.6 mm, length 250 mm) (manufactured by YMC Co., Ltd.)
Column temperature: Constant temperature around 45 ° C. Mobile phase: A mixture of 600 mL of acetonitrile, 400 mL of water and 10 mL of acetic acid, filtered, and flow rate: 1.1 mL / min
Sampling volume: 50 μL

(4) HPLC analysis method for dipotassium glycyrrhizinate Detector: UV absorption photometer (measurement wavelength: 250 nm)
Column: Partisil-10 ODS-3 column (inner diameter 4.6 mm, length 250 mm) (manufactured by GL Sciences Inc.)
Column temperature: Constant temperature around 40 ° C. Mobile phase: Phosphoric acid-triethanolamine buffer solution prepared by adding 1,000 mL of water to 5 g of triethanolamine to dissolve, and adding phosphoric acid to pH 3.0. 6
70 mL and 330 mL of acetonitrile mixed and filtered through flow rate: 1.0 mL / min
Sampling volume: 50 μL

From the results shown in Table 5, 0.5 to 2.0 mass of (A) an alginate having a 1.0% aqueous solution viscosity of 5 to 100 mPa · s and an M / G ratio of 0.5 to 2.0 was obtained. %, (B) 0.2 to 1.2% by mass of sodium carboxymethylcellulose having a degree of etherification of 0.8 to 1.6, (C) the following general formula (1)
_{M n H 3-n PO 4} (1)
(However, M represents Na or K, and n is 1, 2 or 3.)
0.05 to 0.5% by mass of the phosphate represented by formula (D), 45 to 90% by mass of water, and the mass ratio of (A) / (B) is 0.5 to 6%. A liquid composition (Examples 7 to 16) for application to the cervix or interdental region having a pH in the range of 0.0 and a pH in the range of 6.0 to 8.5 at 25 ° C. (Examples 7 to 16) Exhibits excellent effects in all aspects of dischargeability, retention), storage stability (appearance change, pH, viscosity) and thickening effect by Ca ions, and medicinal components (fluorine compounds, anti-inflammatory agents, bactericides) It has been found that the effect of improving the retention of the agent is sufficiently exhibited.

  Examples 17 to 22 are shown below. In addition, the thing from which the viscosity and M / G ratio made from Kibun Food Chemifa Co., Ltd. or Kimika Co., Ltd. differ was used for sodium alginate. CMC, phosphate, ethanol, nonionic surfactant, fluorine compound, anti-inflammatory agent and fungicide were used as described above except for the following. The fragrance | flavor used what was shown in Table 6. In any of these examples, it is excellent in usability (dischargeability, retention), storage stability (appearance change, pH, viscosity) and thickening effect by Ca ions, and further medicinal components (fluorine compounds, anti-inflammatory agents) Thus, a liquid oral composition that sufficiently exhibits the effect of improving the retention of the disinfectant was obtained.

Tranexamic acid; Epsilon aminocaproic acid from Daiichi Pharmaceutical Co., Ltd .; Benzalkonium chloride from Daiichi Chemicals; Triclosan from Nippon Oil &Fats; Hinokitiol from Wako Pure Chemical Industries; Wako Pure Chemical Industries ( Benzethonium chloride manufactured by Wako Pure Chemical Industries, Ltd. Chlorhexidine gluconate (20%); Wako Pure Chemical Industries, Ltd. dl-α-tocophenol acetate; Roche Vitamin Japan Co., Ltd.

[Example 17] Dentifrice (A) Sodium alginate (viscosity: 15 mPa · s, M / G ratio: 1.3)
0.8% by mass
(B) CMC (degree of etherification: 0.9, viscosity; 1,600 mPa · s) 0.6
(C) Sodium monohydrogen phosphate 0.25
(C) Sodium dihydrogen phosphate 0.05
(H) Cetylpyridinium chloride 0.05
(H) Isopropylmethylphenol 0.03
(G) Glycyrrhetinic acid 0.03
(J) Ethanol 5.0
(I) Polyoxyethylene hydrogenated castor oil (EO average added mole number 100) 3.5
Propylene glycol 3.0
Glycerin (85%) 12.0
Sorbit liquid (70%) 15.0
Fragrance C 0.55
Blue No. 1 0.001
Yellow No. 4 0.0001
Caramel color 0.002
Purified water balance
Total 100% by mass
(D) Moisture content 66% by mass
(A) Mass ratio of alginate / (B) CMC 1.3
pH 7.2

  Similar results were obtained even when sodium alginate having a viscosity of 15 mPa · s and an M / G ratio of 0.8, or a viscosity of 50 mPa · s and an M / G ratio of 0.8 was used. Similar results were obtained even when CMC having a degree of etherification of 1.4 and a viscosity of 1,600 mPa · s was used. Further, similar results were obtained even when the fragrances A, B, D, E, and F were used in place of the fragrance C.

[Example 18] Liquid dentifrice (A) Sodium alginate (viscosity: 30 mPa · s, M / G ratio: 0.8)
1.0% by mass
(B) CMC (degree of etherification; 1.4, viscosity; 1,600 mPa · s) 0.5
(C) Sodium monohydrogen phosphate 0.1
(C) Sodium dihydrogen phosphate 0.1
(E) Xanthan gum 0.15
(F) Sodium fluoride 0.05
(G) Epsilon aminocaproic acid 0.03
(H) Triclosan 0.05
(H) Chlorhexidine gluconate (20%) 0.10
(J) Ethanol 8.0
(I) Polyoxyethylene hydrogenated castor oil (EO average addition mole number 60) 1.0
Propylene glycol 2.0
Polyethylene glycol 600 3.0
Glycerin (85%) 15.0
Fragrance D 0.6
Yellow No. 4 0.001
Purified water balance
Total 100% by mass
(D) Moisture content 71% by mass
(A) Mass ratio of alginate / (B) CMC 2.0
pH 6.9

  Similar results were obtained even when sodium alginate having a viscosity of 15 mPa · s and an M / G ratio of 0.8, or a viscosity of 50 mPa · s and an M / G ratio of 1.3 was used. Similar results were obtained even when CMC having a degree of etherification of 0.9 and a viscosity of 1,600 mPa · s was used. Furthermore, the same result was obtained even when the fragrances A, B, C, E, and F were used in place of the fragrance D.

[Example 19] Tooth neck and gum application agent (A) Sodium alginate (viscosity: 50 mPa · s, M / G ratio: 0.8)
0.8% by mass
(B) CMC (etherification degree: 0.9, viscosity; 1,600 mPa · s) 0.5
(C) Sodium monohydrogen phosphate 0.2
(C) Sodium dihydrogen phosphate 0.04
(G) Tranexamic acid 0.05
(H) Benzethonium chloride 0.03
(H) Hinokitiol 0.05
(J) Ethanol 2.0
(I) Polyoxyethylene cetyl ether (EO average addition mole number 20) 0.5
Propylene glycol 3.0
Glycerin (85%) 15.0
Sorbit liquid (70%) 10.0
Allantoin 0.03
Potassium nitrate 0.02
Fragrance D 0.4
Purified water balance
Total 100% by mass
(D) Water content 73 mass%
(A) Mass ratio of alginate / (B) CMC 1.6
pH 7.2

The viscosity as sodium alginate M / G ratio 15 mPa · s was obtained similar results with the existing 1.3. Similar results were obtained even when CMC having a degree of etherification of 1.4 and a viscosity of 1,600 mPa · s was used. Furthermore, the same result was obtained even when the fragrances A, B, C, E, and F were used in place of the fragrance D.

[Example 20] Liquid dentifrice (A) Sodium alginate (viscosity: 10 mPa · s, M / G ratio: 1.3)
1.0% by mass
(B) CMC (degree of etherification; 1.4, viscosity; 1,600 mPa · s) 0.4
(C) Sodium dihydrogen phosphate 0.2
(E) Xanthan gum 0.3
(F) Sodium monofluorophosphate 0.20
(G) Dipotassium glycyrrhizinate 0.05
(G) Acetic acid dl-α-tocophenol 0.03
(H) Triclosan 0.03
(H) Benzalkonium chloride 0.05
(J) Ethanol 4.0
(I) Polyoxyethylene (200) Polyoxypropylene glycol (70)
1.0
Propylene glycol 2.0
Glycerin (85%) 20.0
Sorbit liquid (70%) 10.0
Sodium bicarbonate 0.1
Fragrance E 0.5
Blue No. 1 0.001
Purified water balance
Total 100% by mass
(D) Moisture content 66% by mass
(A) Alginate / (B) CMC mass ratio 2.5
pH 7.5

  Similar results were obtained even when sodium alginate having a viscosity of 30 mPa · s and an M / G ratio of 0.8, or a viscosity of 50 mPa · s and an M / G ratio of 0.8 was used. Similar results were obtained even when CMC having a degree of etherification of 0.9 and a viscosity of 1,600 mPa · s was used. Furthermore, the same result was obtained even when the fragrances A, B, C, D, and F were used in place of the fragrance E.

[Example 21] Liquid dentifrice (A) Sodium alginate (viscosity: 80 mPa · s, M / G ratio: 0.8)
1.2% by mass
(B) CMC (etherification degree: 0.9, viscosity; 1,600 mPa · s) 0.7
(C) Sodium monohydrogen phosphate 0.2
(C) Sodium dihydrogen phosphate 0.1
(G) Tranexamic acid 0.05
(G) Glycyrrhetinic acid 0.03
(H) Chlorhexidine hydrochloride 0.02
(J) Ethanol 2.0
(I) Polyoxyethylene hydrogenated castor oil (EO average added mole number 60) 0.5
(I) Polyoxyethylene hydrogenated castor oil (EO average added mole number 100) 2.0
Silicic anhydride 5.0
Propylene glycol 3.0
Glycerin (85%) 12.0
Sorbit liquid (70%) 15.0
Xylitol 5.0
Fragrance F 0.5
Stannous fluoride 0.05
Yellow No. 4 0.001
Caramel color 0.003
Purified water balance
Total 100% by mass
(D) Water content 59% by mass
(A) Mass ratio of alginate / (B) CMC 1.7
pH 7.0

  Similar results were obtained when sodium alginate having a viscosity of 30 mPa · s and an M / G ratio of 0.8, or a viscosity of 50 mPa · s and an M / G ratio of 1.3 was used. . Similar results were obtained even when CMC having a degree of etherification of 1.4 and a viscosity of 1,600 mPa · s was used. Further, similar results were obtained even when the fragrances A, B, C, D and E were used in place of the fragrance F.

[Example 22] Liquid dentifrice (A) Sodium alginate (viscosity: 15 mPa · s, M / G ratio: 1.3)
0.9% by mass
(B) CMC (degree of etherification; 1.4, viscosity; 1,600 mPa · s) 0.5
(C) Sodium monohydrogen phosphate 0.23
(C) Sodium dihydrogen phosphate 0.04
(E) Xanthan gum 0.15
(F) Sodium monofluorophosphate 0.25
(H) Isopropylmethylphenol 0.03
(H) Cetylpyridinium chloride 0.05
(G) Glycyrrhetinic acid 0.03
(J) Ethanol 6.0
(I) Polyoxyethylene hydrogenated castor oil (EO average added mole number 100) 3.0
Propylene glycol 3.0
Glycerin (85%) 10.0
Sorbit liquid (70%) 15.0
Fragrance A 0.6
Blue No. 1 0.001
Purified water balance <100% total
(D) Moisture content 66% by mass
(A) Mass ratio of alginate / (B) CMC 1.8
pH 7.1

  Similar results are obtained even when sodium alginate having a viscosity of 15 mPa · s and an M / G ratio of 0.8, or a viscosity of 30 mPa · s and an M / G ratio of 0.8 or 1.3 is used. was gotten. Similar results were obtained even when CMC having a degree of etherification of 0.9 and a viscosity of 1,600 mPa · s was used. Furthermore, the same result was obtained even when the fragrances B, C, D, E, and F were used in place of the fragrance A.

It is an experiment flowchart which fractionates sodium alginate into MM fraction, GG fraction, and MG fraction.

Claims (7)

(A) The viscosity of a 1.0 mass% aqueous solution at 20 ° C. is 5 to 100 mPa · s, and the content ratio of the D-mannuronic acid [M] and L-guluronic acid [G] in the molecule (M / G ratio) alginate and 0.5 to 2.0 wt% is but 0.5 to 2.0 in mass ratio,
(B) 0.2 to 1.2% by mass of sodium carboxymethyl cellulose having a degree of etherification of 0.8 to 1.6
And (A) component / (B) component as a mass ratio in the range of 0.5 to 6.0,
(C) The following general formula (1)
_{M n H 3-n PO 4} (1)
(However, M represents Na or K, and n is 1, 2 or 3.)
0.05 to 0.5% by mass of a phosphate represented by
(D) 45-90 mass% of moisture
Compounded, in a pH range of 6.0-8.5 at 25 ° C. of the composition, a liquid oral composition, wherein the viscosity at 25 ° C. is 600~3,400mPa · s. The liquid oral composition according to claim 1, wherein the viscosity of the 1.0 mass% aqueous solution of the component (A) at 20 ° C is 5 to 50 mPa · s. The liquid oral composition according to claim 1 or 2, wherein the blending amount of the abrasive is 0% by mass. The liquid oral composition according to any one of claims 1 to 3, further comprising (E) xanthan gum. And (F) a fluorine compound selected from sodium fluoride and sodium monofluorophosphate and / or (G-1) a water-soluble anti-inflammatory agent selected from tranexamic acid, epsilon aminocaproic acid and glycyrrhizinate. The liquid composition for oral cavity according to any one of claims 1 to 4 . Further, (G-2) a poorly water-soluble anti-inflammatory agent selected from (G-2) glycyrrhetinic acid and dl-α-tocophenol acetate and / or (H) isopropylmethylphenol, triclosan, hinokitiol, cetylpyridinium chloride, benzethonium chloride, benzalco chloride chloride, chlorhexidine gluconate, it contains fungicides selected from chlorhexidine hydrochloride, and (I) any one of claims 1 to 5, characterized in that it contains a nonionic surfactant and / or (J) ethanol 1 The liquid oral composition according to Item. The liquid oral composition according to any one of claims 1 to 6 , wherein the composition is an interdental product applied by an interdental brush, or a cervical or gingival application product applied by a finger. .

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