KR101807905B1 - Liquid oral composition - Google Patents

Abstract

A liquid oral composition containing ascorbic acid phosphate esters is characterized in that the stability of ascorbic acid phosphate esters is improved and a retentive reduction in the retention rate and the generation of sediment are suppressed at the same time, (A) a liquid oral composition containing ascorbic acid phosphoric acid ester or a salt thereof and not containing an abrasive, and a method for stabilizing ascorbic acid phosphate ester or a salt thereof in a composition for oral use and liquid oral composition. (B) an organic acid or a salt thereof, and (C) an orthophosphate, and having a pH of 6.5 to 8.0 and a water content of 60 mass% or more. A liquid oral composition containing the above component (A) and containing no abrasive contains a component (B) and a component (C), and has a pH of 6.5 to 8.0 and a water content of 60 mass% A method for stabilizing ascorbic acid phosphate ester or a salt thereof in the liquid oral composition.

Description

[0001] LIQUID ORAL COMPOSITION [0002]

The present invention relates to a liquid oral composition containing ascorbic acid phosphoric acid ester or a salt thereof and not containing an abrasive. More specifically, the present invention relates to a liquid oral composition comprising ascorbic acid phosphate or a salt thereof, To a liquid oral composition capable of suppressing the occurrence of formulation sediment and having no discomfort and feeling, and a method for stabilizing ascorbic acid phosphate ester or a salt thereof in a liquid oral composition.

Ascorbic acid plays an important role in the expression of various enzyme activities in vivo and is known to have various physiological activities. Especially as a coenzyme of prolyl and lysylhydroxylase and essential for collagen synthesis. Therefore, it is useful for the prevention and treatment of periodontal disease and periodontitis accompanied by destruction of collagen, and various ascorbic acid derivatives have been conventionally developed, and in particular, ascorbic acid phosphate esters and salts thereof Attention is being paid.

However, when the ascorbic acid phosphate ester is incorporated into the oral composition, there is a problem that the residual ratio of the ascorbic acid phosphate ester is lowered over time. Particularly, in a composition for liquid oral cavity such as a mouthwash or liquid toothpaste, a decrease in the residual rate is remarkable because of a large amount of water in the composition, and the decrease in the residual rate is suppressed even after prolonged storage at a high temperature It was very difficult.

In addition, when ascorbic acid phosphate ester is stabilized on the alkali side, maintaining the pH of the composition in the alkaline range is effective for suppressing the decrease of the residual rate. On the other hand, if the pH of the liquid oral composition exceeds 8, There is a problem that when the mouth is put into the mouth, a feeling of discomfort such as sloughing or unusual taste is felt, or sediment becomes easy to occur, and there arises a problem in formulation.

Heretofore, a chelating agent having a carboxyl group and a chelating agent having a phosphoric acid group such as condensed phosphoric acid and phytic acid have been mixed in a patent document 1 (Japanese Patent Application Laid-Open No. 2000-256153) as a technique for stably mixing ascorbic acid phosphate esters , Ascorbic acid or a derivative thereof is prevented from lowering with time. However, a chelating agent having a phosphoric acid group such as condensed phosphoric acid or phytic acid is different from orthophosphate in that it sometimes causes sedimentation with time, and it is a problem to impair the uniform appearance of the liquid oral composition. Patent Document 2 (Japanese Unexamined Patent Publication (Kokai) No. 4-173727) discloses a composition for oral cavity containing an abrasive in ascorbic acid phosphoric acid ester and inhibiting coloration by adding citric acid, a phosphate, a carbonate, a bicarbonate, , The intensity of the coloration does not always coincide with the degree of reduction of the residual ratio of ascorbic acid phosphoric acid esters. Water-insoluble compounds such as abrasives are difficult to be incorporated into liquid oral compositions, and this technique has insufficient decomposition inhibiting effect over time.

(Japanese Patent Application Laid-Open No. 62-63597) discloses a method for inhibiting the formation of sediment in an aqueous solution containing an organic carboxylic acid (salt), an organic phosphoric acid (salt), an organic sulfate Patent Document 4 (Japanese Patent Application Laid-Open No. 2002-255981) discloses an L-ascorbic acid-2-phosphate ester magnesium salt having a reduced content of a calcium compound presumed to be a cause of sedimentation, and a method for producing the same Has been proposed. However, in these techniques, the effect of inhibiting the decomposition of ascorbic acid phosphate ester is low, and it is difficult to simultaneously solve the formation of sediment and decomposition.

Patent Document 1: Japanese Patent Application Laid-Open No. 2000-256153 Patent Document 2: Japanese Patent Application Laid-Open No. 4-173727 Patent Document 3: Japanese Patent Application Laid-Open No. 62-63597 Patent Document 4: JP-A-2002-255981

In view of this, there is a need for a new technique capable of stably maintaining ascorbic acid phosphate esters in a liquid oral composition, solving both of the decrease in the residual rate and occurrence of sedimentation, and providing a preparation with good feeling.

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above circumstances, and it is an object of the present invention to provide a liquid oral composition containing ascorbic acid phosphoric acid esters in which the stability of ascorbic acid phosphoric acid esters is improved and the residual ratio of ascorbic acid phosphoric acid esters It is another object of the present invention to provide a liquid oral composition and a method for stabilizing ascorbic acid phosphate ester or a salt thereof in a composition for liquid oral cavity which are both inhibited from deterioration and occurrence of sediment and have no discomfort and good feeling.

(A) a liquid oral composition containing ascorbic acid phosphate or a salt thereof and containing no abrasive, (B) an organic acid or a salt thereof and C) Orthophosphate is added, the pH at 25 ° C is set to 6.5 to 8.0, and the water content in the composition is set to 60 mass% or more, whereby the stability of ascorbic acid phosphate or its salt and the effect of suppressing sedimentation are satisfactorily maintained .

According to the present invention, there is provided a liquid oral composition containing ascorbic acid phosphoric acid ester or a salt thereof and containing no abrasive, wherein, even when stored at 60 占 폚 for one month in the vicinity of a pH of 8 or less, Ester or a salt thereof can be stabilized and thereby the occurrence of sediment is effectively suppressed while the stability of the ascorbic acid phosphoric acid ester or the salt thereof is excellent over time and the liquid oral solution having a good feeling without discomfort when put in the mouth The present invention has been accomplished on the basis of these findings.

That is, in the prior art, it is difficult to satisfactorily stabilize the ascorbic acid phosphate ester in the range of pH 8 or less in the liquid oral composition containing no abrasive, and the effect of inhibiting the sedimentation of the organic carboxylic acid salt such as citrate is not sufficient . A coloring inhibiting effect by combining citric acid salt and disodium phosphate or the like with ascorbic acid phosphoric acid ester, and a combination of citric acid salt and pyrophosphoric acid surface or tripolyphosphate with ascorbic acid phosphoric acid ester can prevent the residual rate from being lowered It is known. However, by using the organic acid or its salt (B) and (C) orthophosphoric acid in combination and adjusting the pH of the composition to 6.5 to 8.0 and the water content in the composition to 60 mass% or more, , It is possible to effectively stabilize ascorbic acid phosphoric acid ester or a salt thereof and to thereby suppress both the residual rate of ascorbic acid phosphate or its salt and the occurrence of sediment and to provide a good feeling of use, Which is a new discovery of the present inventors.

In addition, although the mechanism (mechanism) of the action is not clear in the present invention, (A) an ascorbic acid phosphoric acid ester or a salt thereof, (B) an organic acid or a salt thereof and (C) orthophosphoric acid, Can act synergistically so that the residual ratio of ascorbic acid phosphate or a salt thereof and the occurrence of sedimentation can be inhibited at the same time.

Accordingly, the present invention provides a liquid oral composition and a method for stabilizing ascorbic acid phosphate ester or a salt thereof in a liquid oral composition as described below.

[One]

(B) an organic acid or a salt thereof and (C) an orthophosphate, in a liquid oral composition containing (A) ascorbic acid phosphate ester or a salt thereof and not containing an abrasive, 6.5 to 8.0, and the water content of the composition is 60 mass% or more.

[2]

The liquid oral composition according to [1], wherein the mixing ratio of the component (B) to the component (C) is 0.1 to 5 as a mass ratio of (B) / (C).

[3]

The liquid oral composition according to (1) or (2), which contains 0.01 to 1% by weight of component (B) and 0.01 to 1% by weight of component (C).

[4]

The liquid oral composition according to [1], [2] or [3], wherein the component (B) is at least one selected from citric acid, malic acid, tartaric acid, succinic acid and salts thereof.

[5]

(B) an organic acid or a salt thereof and (C) an orthophosphate, in a liquid oral composition containing (A) ascorbic acid phosphate ester or a salt thereof and not containing an abrasive, 6.5 to 8.0, and the water content in the composition is 60 mass% or more. The method for stabilizing ascorbic acid phosphoric acid ester or its salt in the composition for liquid oral cavity.

[6]

Wherein the mixing ratio of the component (B) to the component (C) is from 0.1 to 5 as a mass ratio of (B) / (C)

A method of stabilizing a substrate.

According to the present invention, it is possible to stabilize ascorbic acid phosphate or its salt in a liquid oral composition containing ascorbic acid phosphate or a salt thereof and not containing an abrasive even in a region of pH 8 or less, It is possible to provide a composition for liquid oral cavity which is simultaneously inhibited from lowering the residual ratio of cornified phosphoric acid ester or its salt and causing sedimentation, and having no discomfort and feeling good.

Hereinafter, the present invention will be described in more detail.

The liquid oral composition of the present invention is a liquid oral composition containing no abrasive, which comprises (A) an ascorbic acid phosphate ester or a salt thereof, (B) an organic acid or a salt thereof, and (C) an ortho acid salt, Is 60 mass% or more, and the pH at 25 占 폚 is 6.5 to 8.0.

As the ascorbic acid phosphoric acid ester (A) or a salt thereof, it is preferable that one or more of the hydroxyl groups (hydroxyl groups) of the 2, 3, 5 and 6-positions of ascorbic acid are esters of phosphoric acid, polyphosphoric acid, For example, ascorbic acid-2-phosphate ester, ascorbic acid-3-phosphate ester, ascorbic acid-6-phosphate ester and ascorbic acid-2-polyphosphoric acid ester. Include alkali metal salts such as sodium salt, potassium salt, calcium salt and magnesium salt, and alkaline earth metal salts. Particularly, from the viewpoint of the stability of the composition, a phosphoric acid esterified derivative having a hydroxyl group at the second or third position of ascorbic acid is preferable, and a magnesium salt or a sodium salt of ascorbic acid-2-phosphate ester is more preferable.

The amount of the (A) ascorbic acid phosphate ester or its salt is preferably 0.1 to 5% (mass% or less, more preferably 0.2 to 2%) of the entire composition. If the blending amount is less than 0.1%, the preventive effect of periodontal disease may not be fully exerted. If the blend amount is more than 5%, the improvement of the periodontal disease prevention effect is not desired any more. In addition, The sense of discomfort of the user may be increased and the feeling of use may be deteriorated.

The organic acid or its salt as the component (B) is blended with the stabilizer of the component (A), and when used in combination with the component (C), the effect of suppressing the decomposition of the component (A) .

(B) is not particularly limited as long as it is an organic acid to be generally compounded in an oral composition, but di- or tricarboxylic acids such as tartaric acid, malic acid, succinic acid, glutamic acid, adipic acid, aspartic acid and citric acid are preferable. As the salts thereof, sodium salt, potassium salt and the like are preferable. Among them, tartaric acid, malic acid, succinic acid, citric acid or a salt thereof is particularly preferable from the viewpoint that there is no decomposition inhibiting effect of the component (A), sediment retention effect, and discomfort at the time of ingestion, more preferably citric acid or its sodium salt to be.

The organic acid or its salt may be used singly or in combination of two or more kinds. The amount of the organic acid or its salt is preferably 0.01 to 1%, particularly 0.03 to 0.5%, based on the whole composition. If the blending amount is less than 0.01%, the decomposition inhibiting effect and the sediment retention effect of the component (A) may deteriorate. If the blending amount exceeds 1%, the decomposition inhibiting effect of the component (A) There is a case that the feeling of discomfort when the mouth is put in is increased.

The orthophosphate of the component (C) is blended as the stabilizer of the component (A), and when used in combination with the component (B), the effect of suppressing the decomposition of the component (A) Effect.

Examples of the orthophosphate include hydrogen salts such as sodium chloride, potassium phosphate and ammonium phosphate, salts such as sodium chloride, sodium dihydrogenphosphate, sodium dihydrogenphosphate, potassium dihydrogenphosphate, and potassium dihydrogenphosphate . Among them, from the viewpoint of the decomposition inhibiting effect and the sedimentation inhibiting effect of the component (A), a hydrogen salt is preferable, and more preferably, disodium hydrogen phosphate is disodium hydrogen phosphate. Also, the object of the present invention can not be achieved by using a chelating agent having a phosphate group such as pyrophosphate or polyphosphate instead of orthophosphate.

The amount of the orthophosphate compounded is preferably 0.01 to 1%, particularly 0.03 to 0.5%, based on the whole composition. When the blending amount is less than 0.01%, the effect of inhibiting the decomposition of the component (A) may deteriorate. When the blending amount exceeds 1%, the decomposition inhibiting effect and the sediment retention effect of the component (A) There is a case that the feeling of discomfort when the mouth is put in is increased.

The mixing ratio of the component (B) to the component (C) is preferably from 0.1 to 5, particularly from 0.2 to 3 as the weight ratio of the component (B) / the component (C) . When the blend ratio is less than 0.1 or exceeds 5, the decomposition inhibiting effect and the sediment retention effect of the component (A) may not be sufficiently exhibited. Particularly, the mixing ratio is more effective in satisfying the sediment suppressing effect.

The ratio of the component (B) to the component (C) / (A) is preferably 0.05 to 5, more preferably 0.1 to 1 in terms of the mass ratio. Which is more preferable. When the ratio is less than 0.05 or exceeds 5, the decomposition inhibiting effect of the component (A) may not be sufficiently exhibited.

The composition of the present invention is generally mixed with purified water as a solvent. The water content is at least 60%, preferably at least 75%, and preferably less than 99.8% of the total composition. If the water content is less than 60%, the user may feel slippery or sticky in the oral cavity, and stimulation in the oral cavity due to other solvents such as alcohol may become large.

The pH of the composition is 6.5 to 8.0 (25 캜), more preferably 7.0 to 7.8. When the pH is less than 6.5, the decomposition inhibiting effect of the component (A) is deteriorated. When the pH is more than 8.0, the precipitate can not be satisfactorily suppressed, and there is a possibility that the feeling of discomfort,

Further, the pH of the composition may sometimes be 6.5 to 8.0, but it may be adjusted within the above range using a pH adjuster as needed. As the pH adjusting agent, a pH adjusting agent such as sodium hydroxide, hydrochloric acid, sodium carbonate, sodium hydrogencarbonate, boric acid or a salt thereof can be used. Of these, sodium hydroxide, potassium hydroxide and hydrochloric acid are preferably used. The amount of these pH adjusting agents may be adjusted so long as the pH can be adjusted within the above range.

The liquid oral composition of the present invention may further comprise a solvent, a wetting agent, and the like as needed. As the solvent, a polyhydric alcohol such as propylene glycol and a lower alcohol such as ethanol may be mixed. The blending amount of these solvents is usually 0 to 30%, particularly preferably 2 to 20%, of the whole composition.

In addition, the liquid oral composition of the present invention can obtain the effect of the present invention even when the composition contains substantially no ethanol (that is, the ethanol content in the composition is 0.01% or less, particularly 0 to 0.0001%).

Examples of the wetting agent include polyhydric alcohols such as sorbitol, glycerin, ethylene glycol, polyethylene glycol, xylitol and erythritol, and sugar alcohols. The blending amount is usually 0 to 20% of the whole composition.

The liquid oral composition of the present invention is a liquid oral composition which does not contain an abrasive, and can be suitably prepared and applied as a formulations such as a cleanser, a liquid toothpaste, a tooth gel, a cleanser, a thickening agent, . The cleaning agent may be either transparent or opaque, but it is preferably a uniform liquid containing no precipitate or suspended matter. In addition, in addition to the above-mentioned components, appropriate known components may be blended as required in response to the form of the composition. For example, a thickener, a surfactant, an antiseptic, a sweetener, a coloring agent, a perfume, an active ingredient and the like may be added in addition to the above-mentioned solvent and wetting agent.

Examples of the thickening agent include carboxymethylcellulose sodium, hydroxyethylcellulose and the like. The blending amount of the thickener is usually 0 to 5%, particularly 0.1 to 3%.

The surfactant may be a surfactant that is commonly used in oral compositions, and the blending amount of the surfactant is usually in the range of 0.1 to 10%.

Examples of the preservative include parabens and the like. As the sweetening agent, saccharin sodium and the like can be mentioned. As the coloring agent, a water-soluble coloring matter may be mentioned.

As the fragrance, it is possible to use a known fragrance used in oral hygiene products such as spearmint oil, natural spices such as peppermint oil, and separately prepared fragrance such as carnauba and anethole, and preparative fragrance including individual fragrance and / or natural fragrance And it is not limited to the fragrance described in the examples. Usually, the blending amount is in the range of 0.00001 to 1%.

In addition to the ascorbic acid phosphoric acid ester or its salt as the component (A), an effective amount may be mixed with an effective amount, for example, an anti-inflammatory agent, an enzyme, a fluoride, a bactericide or the like within the range not hindering the effect of the present invention.

Example

EXAMPLES Hereinafter, examples and comparative examples are shown and the present invention is specifically described, but the present invention is not limited to the following examples. In the following examples,% represents mass%, unless otherwise specified. The pH in the table was measured using a pH meter (No. Hm-30S) manufactured by Toa Gosei Kogyo Co., Ltd. immediately after the adjustment, and the pH value after 25 minutes was 3 minutes.

[Practical example, comparative example]

A liquid oral composition having the compositions shown in Tables 1 to 3 was prepared by the following method to obtain a uniform liquid oral composition. The obtained liquid oral composition was transparent. These liquid oral compositions were evaluated by the following methods. The results are shown in Tables 1 to 3.

(1) Method for producing liquid oral composition

To 850 g of purified water, ascorbic acid phosphoric acid esters and other components were mixed at room temperature and stirred for 1 hour until the ascorbic acid phosphoric acid ester was completely dissolved. If the pH does not fall within the range of 6.5 to 8.0, the pH is adjusted with sodium hydroxide, hydrochloric acid, etc., and the total amount of the composition is adjusted to 1,000 g. In addition, a 10% aqueous solution of sodium hydroxide and hydrochloric acid was added so that the pH was in the above range.

(2) Evaluation of decomposition inhibiting effect of component (A)

250 ml of a 250 ml bottle of the composition was filled in a 250 ml container and stored at 60 ° C and -5 ° C for 1 month. Then, 10 mmol / l phosphate buffer (1.5 mmol / l potassium dihydrogen phosphate, 23.5 mmol / (PU1580 autosampler manufactured by Shimadzu Corporation: SIL-10A manufactured by Shimadzu Corporation, UV detector: SPD-6A manufactured by Shimadzu Corporation), recording (diluted with distilled water, pH 8) Apparatus: C-R4A manufactured by Shimadzu Corporation) was used for quantitative determination by the absolute calibration curve method. In the mobile phase, a column of 25 mmol / l potassium dihydrogenphosphate + 5 mmol / l tetrabutylammonium sulfate / acetonitrile = 91/9 (volume ratio), a column having a diameter of about 4.6 mm and a length of about 150 mm, (For example, TSK-gel ODS-80Ts (manufactured by Tosoh Corporation)), a column temperature of about 50 ° C, a detection wavelength of 240 nm, and a flow rate of 0.8 ml / min Respectively. The concentration of ascorbic acid phosphate ester in the product preserved at 60 ° C was calculated and the residual rate when the content in the product stored at -5 ° C was taken as 100% was determined.

Criteria for Evaluation of the Decomposition of Ascorbic Acid Phosphate Ester

&Amp; cir &: The residual ratio of the composition is 90% or more

?: Residual ratio of the composition is 80% or more and less than 90%

?: Residual ratio of the composition is not less than 70% and less than 80%

X: Residual ratio of the composition is less than 70%

(3) Evaluation of sediment inhibition effect

250 ml of the composition was filled in 250 ml of PET bottle and stored at 60 占 폚 for 1 month. After the PET container was gently swapped, the sediment was transferred to a PET container (control product) filled with purified water And visually judged according to the following criteria.

Evaluation criteria of sedimentation inhibition effect

◎: There is no settling sediment

○: Thin sediment is slightly accepted but no problem

△: Precipitation deposits are clearly recognized

X: Residual sediment is recognized without transposing the PET container

(4) Evaluation of no incongruity when we put in mouth

10 subjects who were sensitive to oral mucosa showed that the composition was kept in a mouth of about 10 ml and the mouth feel felt in the oral cavity for about 20 seconds was compared with that of the control (in the same composition as in Example 1, sodium hydroxide To pH 9), and the sensory evaluation was carried out according to the following criteria.

Evaluation standard of no incongruity when we put in mouth

4: Significantly less discomfort

3: The feeling of discomfort was low and there was no problem

2: There was an equal discomfort

1: I felt a remarkable discomfort.

Criteria

◎: 3.5 points or more

○: 3.0 points or more and less than 3.5 points

△: 2.0 points or more and less than 3.0 points

×: less than 2.0 points

The details of the raw materials used are the same as in the following.

Phosphoric acid-L-ascorbylmagnesium: manufactured by Wako Pure Chemical Industries, Ltd. for biochemical

Sodium phosphate-L-ascorbic acid: manufactured by DSM Nutrition Japan Product name Stay C50

Citric acid monohydrate: manufactured by Fuso Kagaku Kogyo Co., Ltd., citric acid, and other raw materials grades (quasi-drugs)

Citric acid 3 sodium dihydrate: manufactured by Fuso Chemical Industry Co., Ltd., sodium citrate,

Sodium malate · 0.5 hydrate: manufactured by Kanto Chemical Co., Limited

Sodium succinate 2: Kanto Chemical Co., Ltd. limited express

L-tartaric acid: manufactured by Kanto Chemical Co., Limited

Sodium dihydrogenphosphate, Sodium hydrogenphosphate, Other grades

Boric acid: Kanto Chemical Co. Limited (comparative product)

Carbonic acid: Kantou Chemical Co. Limited (comparative product)

Sodium pyrophosphate: Manufactured by Taihei Chemical Industry Co., Ltd. and other grades (comparative products)

Polyphosphoric acid: manufactured by Taihei Chemical Industry Co., Ltd., sodium polyphosphate,

Glycerin: Made by Lion Catmilk

Propylene glycol: manufactured by Asahi Kasei

Sodium hydroxide: manufactured by Kanto Kagaku Co., Ltd., sodium hydroxide, diluted to 10%

Hydrochloric acid: diluted to 10% with Kanto Chemical Co., hydrochloric acid, and special grade, mixed

[Table 1-1]

[Table 1-2]

[Table 2-1]

[Table 2-2]

[Table 3]

Claims (6)

(A) at least one organic acid or salt thereof selected from citric acid, malic acid, tartaric acid, succinic acid and salts thereof, and (B) at least one organic acid selected from the group consisting of (C) an orthophosphate, and having a pH of 6.5 to 8.0 at 25 DEG C, and the water content in the composition is 60 mass% or more. The method according to claim 1,
Wherein the mixing ratio of the component (B) to the component (C) is from 0.1 to 5 as a mass ratio of (B) / (C). 3. The method according to claim 1 or 2,
0.01 to 1% by weight of component (B), and 0.01 to 1% by weight of component (C). 3. The method according to claim 1 or 2,
Wherein the pH at 25 DEG C is 6.5 to 7.9. (A) at least one organic acid or salt thereof selected from citric acid, malic acid, tartaric acid, succinic acid and salts thereof, and (B) at least one organic acid selected from the group consisting of (C) an orthophosphoric acid salt, and the pH at 25 ° C is from 6.5 to 8.0, and the water content in the composition is 60 mass% or more. Method of stabilizing salt. 6. The method of claim 5,
Wherein the mixing ratio of the component (B) to the component (C) is from 0.1 to 5 as a mass ratio of (B) / (C).