Method for suppressing foaming of liquid composition

Abstract

To provide a method for suppressing foaming of a liquid composition comprising a quaternary ammonium salt or its hydrate and water-soluble azulene or its pharmaceutically acceptable salt or its hydrate.SOLUTION: There is provided a defoaming method of a liquid composition comprising (A) a quaternary ammonium salt or its hydrate and (B) water-soluble azulene or its pharmaceutically acceptable salt or its hydrate by the inclusion of (C) tannic acid or its salt. The tannic acid or its salt preferably is a cetylpyridinium salt and the water-soluble azulene or its pharmaceutically acceptable salt or its hydrate preferably is azulenesulfonic acid.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a method for suppressing foaming of a liquid composition by adding tannic acid or a salt thereof, and a liquid composition with suppressed foaming.

Background Art

[0002] Cetylpyridinium and its salts have been conventionally used in mouthwashes for sterilization in the oral cavity. Azulene sulfonic acid and its salts have been conventionally used in mouthwashes to suppress inflammation of the oral mucosa as an anti-inflammatory agent.

[0003] Cetylpyridinium, which is a kind of quaternary ammonium salt, is a kind of cationic surfactant and slightly foams when used for gargling, but there is no problem in its use. Also, azulene sulfonic acid foams less than cetylpyridinium, which is a kind of quaternary ammonium salt, and there is also no problem when used for gargling. However, when gargling with a liquid composition containing cetylpyridinium, which is a kind of quaternary ammonium salt, and azulene sulfonic acid, foaming (frothing) becomes extremely strong, and the foam may overflow from the mouth, which has been a major problem in use. Furthermore, excessive foaming during use has made users feel uneasy and has hindered the safe use of mouthwashes.

[0004] In response to such problems, the applicants of the present application have also conducted research and development, and when using a liquid composition containing a quaternary ammonium salt or its hydrate and azulene sulfonic acid, they have studied a method for reducing the generated foam, and have shown that by adding glycyrrhizic acid or a salt thereof to the liquid composition, foaming can be suppressed when using the liquid composition (Patent Document 1).

[0005] On the one hand, tannic acid is a type of tannin, a polyphenol widely present in the plant kingdom. It has an astringent effect and has conventionally been used in antidiarrheal drugs, antiperspirants, etc. However, until now, there have been no known cases of its use as a gargle or mouthwash for oral use, nor have there been any known cases of its use to prevent foaming in a liquid composition.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0007] When gargling with a liquid composition containing a quaternary ammonium salt such as cetylpyridinium or its hydrate and azulenesulfonic acid, foaming becomes extremely strong, and the foam may overflow from the mouth, presenting a major problem in use. Furthermore, excessive foaming during use made it difficult for the user to use.

[0008] The present invention aims to solve the problem of strong foaming when gargling with a liquid composition containing a quaternary ammonium salt such as cetylpyridinium or its hydrate and azulenesulfonic acid, and an object thereof is to suppress the foaming of a liquid composition containing (A) a quaternary ammonium salt or its hydrate and (B) water-soluble azulene or a pharmaceutically acceptable salt thereof or its hydrate.

Means for Solving the Problems

[0009] As a result of intensive studies on defoaming the foam generated in a liquid composition containing (A) a quaternary ammonium salt or its hydrate and (B) a water-soluble azulene or its pharmaceutically acceptable salt or its hydrate, it has been found that by adding (C) tannic acid or its salt to the liquid composition containing (A) a quaternary ammonium salt or its hydrate and (B) a water-soluble azulene or its pharmaceutically acceptable salt or its hydrate, the foam can be defoamed, and the present invention has been completed.

[0010] That is, the present invention provides the following. [1] A defoaming method by containing (C) tannic acid or its salt in a liquid composition containing (A) a quaternary ammonium salt or its hydrate and (B) a water-soluble azulene or its pharmaceutically acceptable salt or its hydrate; [2] The defoaming method of the liquid composition according to [1], wherein the content of tannic acid or its salt is 0.2 mg to 500 mg / 100 ml in the liquid composition; [3] The defoaming method of the liquid composition according to [1] or [2], wherein the tannic acid or its salt is tannic acid; [4] The defoaming method of the liquid composition according to any one of [1] to [3], wherein (A) the quaternary ammonium salt or its hydrate is a cetylpyridinium salt; [5] The defoaming method of the liquid composition according to any one of [1] to [4], wherein (B) the water-soluble azulene or its pharmaceutically acceptable salt or its hydrate is azulene sulfonic acid; [6] An antifoaming agent containing (C) tannic acid or its salt, which is used for a liquid composition containing (A) a quaternary ammonium salt or its hydrate and (B) a water-soluble azulene or its pharmaceutically acceptable salt or its hydrate; [7] The antifoaming agent according to [6], wherein the content of tannic acid or its salt is 0.2 mg to 500 mg / 100 ml in the liquid composition; [8] The antifoaming agent according to [6] or [7], wherein the tannic acid or its salt is tannic acid; [9] The method for defoaming a liquid composition according to any one of [6] to [8], wherein the quaternary ammonium salt or its hydrate is cetylpyridinium salt;

[10] The method for defoaming a liquid composition according to any one of [6] to [9], wherein the water-soluble azulene or its pharmaceutically acceptable salt or its hydrate is azulenesulfonic acid;

[11] A liquid composition having suppressed foaming, containing (A) a quaternary ammonium salt or its hydrate, (B) a water-soluble azulene or its pharmaceutically acceptable salt or its hydrate, and (C) tannic acid or its salt;

[12] The liquid composition according to

[11] , wherein the content of tannic acid or its salt is 0.2 mg to 500 mg / 100 ml in the liquid composition;

[13] The liquid composition according to

[11] or

[12] , wherein the content of (A) the quaternary ammonium salt or its hydrate is 3 to 7 mg / 100 ml in the liquid composition;

[14] The liquid composition according to any one of

[11] to

[13] , wherein the quaternary ammonium salt or its hydrate is cetylpyridinium salt;

[15] The liquid composition according to any one of

[11] to

[14] , wherein the water-soluble azulene or its pharmaceutically acceptable salt or its hydrate is azulenesulfonic acid;

[16] The liquid composition according to any one of

[11] to

[15] , wherein the content of (B) the water-soluble azulene or its pharmaceutically acceptable salt or its hydrate is 1 to 10 mg / 100 ml in the liquid composition;

[17] The liquid composition according to any one of

[11] to

[16] , wherein the liquid composition is a gargle, a mouthwash, an eye drop, a spray or an oral medicine. [Effect of the Invention]

[0011] According to the present invention, in a liquid composition containing (A) a quaternary ammonium salt or its hydrate and (B) a water-soluble azulene or its pharmaceutically acceptable salt or its hydrate, by containing (C) tannic acid or its salt, foaming in the liquid composition can be suppressed (defoamed).

Brief Description of the Drawings

[0012]

Figure 1

Modes for Carrying Out the Invention

[0013] Hereinafter, the content of the present invention will be described in detail. In the present invention, foaming refers to the foaming of a liquid composition, and means that "bubbles" in a state where gas is enclosed in a liquid form a "foam" state in which a large number gather on the liquid surface of the liquid composition and are closely present through a thin film. This foaming phenomenon is determined by two parameters: the ease of foaming (foaming power of bubbles) and the difficulty of disappearance of bubbles (stability of bubbles). On the other hand, "suppression of foaming" in the present invention is used synonymously with "defoaming" in this specification, but is caused by reducing either or both of the "foaming power of bubbles" or the "stability of bubbles" to destabilize the physical properties of the foam.

[0014] The present invention can suppress, that is, defoam, the foaming occurring in a liquid composition by applying (C) tannic acid or a salt thereof to a liquid composition containing (A) a quaternary ammonium salt or a hydrate thereof and (B) a water-soluble azulene or a pharmaceutically acceptable salt thereof or a hydrate thereof.

[0015] Each component contained in the liquid composition to which the method of the present invention can be applied and the content of each component only need to be included in the concentration range of each component described in this specification when actually used. The liquid composition to which the method of the present invention can be applied is · A mode in which each component contained is placed in a container in a state where it is adjusted to a desired concentration and taken out from the container and used as it is, · Each component contained is placed in a container in a state where its concentration is adjusted to a higher concentration than the desired concentration, and when in use, the user dilutes it appropriately with water to adjust each component contained to the desired concentration for use. · A mode in which the drug is separated, divided and supplied into a plurality of containers, and the drugs are mixed when in use. · A mode in which the drug is separated, divided and supplied into a plurality of containers, and after the drugs are mixed when in use, it is further diluted with water. For example, it is possible to take any commercial form or method for preparing a liquid composition. The content of each component described below in this specification is for when in use.

[0016] The quaternary ammonium salt or its hydrate used as component (A) exhibits a bactericidal action. For example, by gargling with an aqueous solution containing cetylpyridinium chloride hydrate, which is an example of a quaternary ammonium salt or its hydrate, the growth of bacteria in the oral mucosa can be suppressed, the inflammation of the throat can be alleviated, and the effects of preventing periodontal disease and halitosis are known.

[0017] As the quaternary ammonium salt of the present invention, cetylpyridinium salt, benzethonium chloride, benzalkonium chloride, etc. can be used. Among them, cetylpyridinium salt is preferable, and as the cetylpyridinium salt, cetylpyridinium chloride is more preferable. For example, 1-hexadecylpyridinium chloride, which is cetylpyridinium chloride hydrate, is preferable.

[0018] The content of the quaternary ammonium salt or its hydrate in the present invention is, for example, as cetylpyridinium chloride hydrate, 0.1 mg / 100 ml to 20 mg / 100 ml, preferably 1 to 10 mg / 100 ml, more preferably 3 to 7 mg / 100 ml, based on the total volume of the liquid composition.

[0019] The water-soluble azulene used as component (B), or a pharmaceutically acceptable salt thereof or a hydrate thereof, has an anti-inflammatory effect. For example, by gargling with an aqueous solution in which sodium azulenesulfonate, which is an example thereof, is diluted, it is known to have an effect of relieving tonsillitis, pharyngitis, stomatitis, and gingivitis.

[0020] As the water-soluble azulene used in the present invention, azulenesulfonic acid is preferable. As the salt of the water-soluble azulene, any salt that forms a salt with the water-soluble azulene can be used, but a sodium salt is preferable, and sodium azulenesulfonate is preferably used.

[0021] As the water-soluble azulene of the present invention, or a pharmaceutically acceptable salt thereof or a hydrate thereof, sodium 1,4-dimethyl-7-isopropylazulene-3-sulfonate and its hydrate, which are sodium azulenesulfonate, are preferable.

[0022] The content of the water-soluble azulene in the present invention, or a pharmaceutically acceptable salt thereof or a hydrate thereof, is, for example, as sodium azulenesulfonate hydrate, 0.01 mg / 100 ml to 50 mg / 100 ml, preferably 0.5 to 20 mg / 100 ml, more preferably 1 to 10 mg / 100 ml, based on the total volume of the liquid composition.

[0023] As the tannic acid or a salt thereof used as component (C), tannic acid, albumin tannate, berberine tannate, etc. can be used, but tannic acid is more preferable. Also, there are pharmaceutical-grade and food-grade tannic acid or its salts. In the present invention, since it is used as an oral liquid composition (for example, a gargle), either grade can be used.

[0024] In the present invention, the content of tannic acid or its salt is, for example, in the case of tannic acid, tannic acid is added in a dose of 0.2 mg / 100 ml to 500 mg / 100 ml, preferably 0.5 mg / 100 ml to 200 mg / 100 ml, more preferably 4 to 100 mg / 100 ml, based on the total volume of the liquid composition of component (A) and component (B).

[0025] In the present invention, the liquid composition contains a solvent capable of dissolving the above-mentioned component (A), component (B) and component (C). Since both component (A), component (B) and component (C) are readily soluble or soluble in water and ethanol, for example, lower alcohols such as ethanol, glycerin, isopropanol, etc. can be used as the solvent. Further, purified water can be used in combination with the lower alcohol. The solvent may contain additives such as 8-acetyl sucrose.

[0026] The liquid composition may contain any other components as long as the effects of the present invention are not impaired. Representative examples of the optional components are exemplified below: As the bactericide, for example, benzalkonium chloride, benzethonium chloride, etc. can be used; As the flavoring agent, for example, saccharin sodium hydrate, menthol, camphor, peppermint oil, lemon oil, perilla oil, eucalyptus oil, cinnamon oil, clove oil, vanillin, fragrance, etc. can be used; As the stabilizer, for example, tocopherol, macrogol, etc. can be used; As the sugar alcohols, for example, xylitol, sorbitol, glycerin, etc. can be used; As the chelating agent, for example, sodium edetate, calcium disodium edetate, and their hydrates, etc. can be used; As the surfactant, for example, sodium lauryl sulfate, polysorbate, polyoxyethylene hydrogenated castor oil, etc. can be used; As the isotonic agent, for example, inorganic salts such as sodium chloride, polyhydric alcohols such as propylene glycol, etc. can be used; As the preservative, for example, parabens, thymol, etc. can be used; Any component is not limited to these, and various additives other than the above can be appropriately used. Also, the purpose of adding these components is not limited to the above.

[0027] The method for preparing the liquid composition is not particularly limited, and known methods can be used. Also, regarding the mixing order of each component, it can be appropriately considered according to the solubility in the solvent.

[0028] The usage form of the liquid composition of the present invention is not particularly limited, and examples include gargles (mouthwashes), oral rinses, sprays, coating agents, eye drops, oral medications such as stomach medicines, etc. For example, when the present invention is used as a gargle, by diluting the present invention with water and holding it in the mouth to wash the throat and oral cavity, it can relieve inflammation of the throat mucosa and oral cavity, suppress the growth of bacteria, and expect effects such as prevention of infectious diseases and prevention of bad breath.

[0029] Examples are shown below to explain the present invention in more detail, but these do not limit the scope of the present invention and can be changed without departing from the gist of the present invention.

Examples

[0030] Example 1: Preparation of liquid compositions and their respective foaming properties This example was conducted for the purpose of preparing liquid compositions containing tannic acid at various concentrations and experimentally showing the foaming characteristics of each.

[0031] First, each liquid composition with the component composition shown in Table 1 was prepared. Each liquid composition was prepared by mixing each component (mg) in the table, adding purified water and dissolving, and making the total volume 100 ml.

[0032]

Table 1

[0033] 25 ml was taken out from each of the obtained liquid compositions and placed in a round-bottom glass container (Maru EM Co., Ltd.) with an outer diameter of 35 mm, an inner diameter of 20.3 mm, a height of 105 mm, and a capacity of 50 ml. With the container sealed, reciprocal stirring was carried out for 2 minutes at a speed of 210 reciprocations per minute with a distance of 40 mm in the long axis direction. Immediately after stirring, the height of the foam from the liquid surface was measured as an index of the foaming degree. The multiple comparison test of the obtained results was carried out by the Tukey-Kramer method.

[0034] The results are shown in Fig. 1. As shown in Fig. 1, in all the formulations shown in Formulation Examples 1 to 9, the height of the foam, which is an index of the foaming degree, was significantly lower than that in Comparative Example 1 (p < 0.01). The addition of tannic acid suppressed foaming, and the effect was maximized at 4 to 100 mg / 100 mL (Formulation Examples 4 to 7).

[0035] Example 2: Sensory evaluation of the foaming properties of liquid compositions This example was conducted for the purpose of the user's sensory evaluation of the degree of foaming of each liquid composition when actually gargling using the liquid compositions prepared in Example 1.

[0036] An appropriate amount of each of the liquid compositions shown in Comparative Example 1 and Formulation Examples 1 to 9 was taken into the mouth and actual gargling was performed, and the degree of foaming at that time was evaluated. Incidentally, tannic acid is an astringent component. For the ones with a concentration of 200 mg / 100 mL in Formulation Example 8 and 500 mg / 100 mL in Formulation Example 9, all the subjects were unable to actually perform gargling. On the other hand, no astringency that would cause problems during use was felt up to a concentration of 40 mg / 100 mL. Also, at a concentration of 100 mg / 100 mL in Formulation Example 7, a slight astringency was felt, but no strong astringency that would cause problems in gargling was felt.

[0037]

Table 2

[0038] As a tendency, regarding Formulation Examples 2 to 7, as a result of the evaluation, the foaming problem of the liquid composition has been improved to the extent that foaming is not a concern. In particular, regarding Formulation Examples 3 to 7, it was considered that the suppression of foaming was good. In an attempt to quantify this tendency, during the above sensory evaluation, -2 points were assigned to ×, -1 point to △, 0 point to ○, and 1 point to ◎ for the evaluation symbols of the subjects, and Table 2 above was converted into score values.

[0039] [Table 3]

[0040] As a result, it was confirmed that the converted score values increased for each formulation example compared to Comparative Example 1. In particular, regarding Formulation Examples 3 to 7, it was confirmed that the converted score values were also clearly high. Therefore, the above tendency could be numerically confirmed. [Industrial Applicability]

[0041] According to the present invention, even in a liquid composition containing (A) a quaternary ammonium salt or its hydrate and (B) a water-soluble azulene or its pharmaceutically acceptable salt or its hydrate, by applying (C) tannic acid or its salt, foaming in the liquid composition can be suppressed (defoamed).

Claims

1. In a liquid composition containing (A) a quaternary ammonium salt or its hydrate and (B) a water-soluble azulene or its pharmaceutically acceptable salt or its hydrate, a defoaming method by containing (C) tannic acid or its salt.

2. The defoaming method of the liquid composition according to Claim 1, wherein the content of tannic acid or its salt is 0.2 mg to 500 mg / 100 ml in the liquid composition.

3. The defoaming method of the liquid composition according to Claim 1 or 2, wherein tannic acid or its salt is tannic acid.

4. The defoaming method of the liquid composition according to any one of Claims 1 to 3, wherein (A) the quaternary ammonium salt or its hydrate is a cetylpyridinium salt.

5. The defoaming method of the liquid composition according to any one of Claims 1 to 4, wherein (B) the water-soluble azulene or its pharmaceutically acceptable salt or its hydrate is azulenesulfonic acid.

6. An antifoaming agent containing (C) tannic acid or its salt, which is used for a liquid composition containing (A) a quaternary ammonium salt or its hydrate and (B) a water-soluble azulene or its pharmaceutically acceptable salt or its hydrate.

7. The antifoaming agent according to Claim 6, wherein the content of tannic acid or its salt is 0.2 mg to 500 mg / 100 ml in the liquid composition.

8. The antifoaming agent according to Claim 6 or 7, wherein tannic acid or its salt is tannic acid.

9. The antifoaming agent according to any one of Claims 6 to 8, wherein (A) the quaternary ammonium salt or its hydrate is a cetylpyridinium salt.

10. The antifoaming agent according to any one of Claims 6 to 9, wherein (B) the water-soluble azulene or its pharmaceutically acceptable salt or its hydrate is azulenesulfonic acid.

11. A liquid composition with suppressed foaming, containing (A) a quaternary ammonium salt or its hydrate, (B) a water-soluble azulene or its pharmaceutically acceptable salt or its hydrate, and (C) tannic acid or its salt.

12. The liquid composition according to Claim 11, wherein the content of tannic acid or its salt is 0.2 mg to 500 mg / 100 ml in the liquid composition.

13. The liquid composition according to Claim 11 or 12, wherein the content of (A) the quaternary ammonium salt or its hydrate is 3 to 7 mg / 100 ml in the liquid composition.

14. The liquid composition according to any one of claims 11 to 13, wherein the quaternary ammonium salt or its hydrate is cetylpyridinium salt.

15. The liquid composition according to any one of claims 11 to 14, wherein the water-soluble azulene or its pharmaceutically acceptable salt or its hydrate is azulenesulfonic acid.

16. The liquid composition according to any one of claims 11 to 15, wherein the content of the water-soluble azulene or its pharmaceutically acceptable salt or its hydrate is 1 to 10 mg / 100 ml in the liquid composition.

17. The liquid composition according to any one of claims 11 to 16, wherein the liquid composition is a gargle, a mouthwash, an eye drop, a spray or an oral medicine.

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