mouthwash

Abstract

To provide a mouthwash mixed with povidone iodine (PVPI), containing PVPI in a higher concentration than a conventional product (7%), and to provide a method for producing the same.SOLUTION: A method for producing a povidone-iodine-containing mouthwash containing povidone iodine in an amount of 10% by mass or more based on the total amount (100% by mass) of the mouthwash, the method comprising the steps of: 2.14 4.28, A method for producing a gargle, comprising the steps of: dispersing PVPI in PG to obtain a dispersion; and mixing the dispersion with a mixed solution a1 in which at least one selected from the group consisting of ethanol, glycerin, D-sorbitol solution (70%), saccharin sodium, and 1-menthol is dissolved in water, or a mixed solution a1 in which potassium iodine is further dissolved in the mixed solution a2.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a mouthwash (gargle) containing a high concentration of povidone-iodine and a method for producing the same. [Background technology]

[0002] Povidone-iodine (PVPI) has a strong bactericidal effect derived from free iodine and is used in a wide range of applications, including as a mouthwash, disinfection during surgical procedures, and disinfection of wounds on the skin and mucous membranes. Known efficacy of PVPI-containing mouthwashes includes preventing infections of pharyngitis, tonsillitis, stomatitis, and oral wounds, including tooth extraction wounds, as well as sterilizing, disinfecting, and cleansing the oral cavity and throat, and eliminating bad breath. Commercially available PVPI-containing mouthwashes generally contain 70 mg of PVPI per mL (7% PVPI, 7 mg of available iodine), and are diluted 15 to 30 times (2 to 4 mL of the original solution is diluted with approximately 60 mL of water) and used as gargles several times a day (Non-Patent Document 1). [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Povidone-iodine gargle solution "Isodine (registered trademark) Gargle Solution 7%" package insert, 2023, pp. 1-2 Summary of the Invention [Problem to be solved by the invention]

[0004] Mouthwashes containing PVPI are commercially available in volumes as small as 30 mL and as large as 500 mL. However, while small volumes are convenient for portability, they tend to run out quickly, while larger volumes can be difficult to find space for in bathrooms and are not very portable. Therefore, it is possible to increase the concentration of PVPI in mouthwash, thereby reducing the volume (container size) and improving portability. However, mouthwashes with high concentrations of PVPI tend to produce lumps during production, making it difficult to achieve a uniform composition.

[0005] The present invention provides a povidone-iodine (PVPI)-containing mouthwash containing PVPI at a higher concentration than conventional products (7%), and a method for producing the same. [Means for solving the problem]

[0006] That is, the present invention covers the following [1] to [4]. [1] A method for producing a povidone-iodine-containing mouthwash, which contains 10% by mass or more of povidone-iodine relative to the total amount (100% by mass) of the mouthwash, a step of dispersing povidone-iodine (PVPI) in propylene glycol (PG) so that the mass ratio of PVPI to PG is 1:2.14 to 4.28 to obtain a dispersion; mixing the dispersion with a mixed solvent a1 obtained by dissolving at least one selected from the group consisting of ethanol, glycerin, D-sorbitol solution (70%), saccharin sodium, and l-menthol in water, or a mixed solvent a2 obtained by further dissolving potassium iodide in the mixed solvent a1; How to make mouthwash. [2] A povidone-iodine-containing mouthwash containing the following ingredients (total amount 100g). Povidone iodine 10-20g Propylene glycol 20-80g Sodium saccharin 0.05~5g l-menthol 0~5g D-sorbitol liquid (70%) 0-60g Glycerin 0-60g Ethanol 0-60g Potassium iodide 0-5g 1~60g water [3] A povidone-iodine-containing mouthwash described in [2], which contains the following ingredients (total amount 100g): Povidone iodine 14g 30g propylene glycol Sodium saccharin 0.16g 5-30g glycerin Ethanol 0-50g Potassium iodide 0-5g 1~50g water [4] A povidone-iodine-containing mouthwash described in [2], which contains the following ingredients (total amount 100g): Povidone iodine 14g 30g propylene glycol Sodium saccharin 0.16g l-menthol 0.24g 1-30g glycerin 10-50g of ethanol Potassium iodide 0-5g 1~36g water [Effects of the Invention]

[0007] According to the present invention, it is possible to provide a mouthwash containing povidone-iodine (PVPI) at a concentration approximately twice as high as that of conventional products (7%). Furthermore, according to the present invention, a mouthwash containing a high concentration of PVPI can be produced with a uniform composition free of lumps and the like. Furthermore, since the mouthwash of the present invention contains a high concentration of PVPI, the amount of ethanol used as a solvent and other additives can be reduced. In addition, the product volume (container size) can be made smaller than conventional products, ensuring a sufficient amount of medicine even in a volume suitable for portability. Furthermore, when placed in a bathroom or other area, the space required for storage can be reduced, making it unobtrusive even when kept on hand, and it is not only highly usable but also expected to encourage the development of gargling habits, which in turn is expected to help prevent infectious diseases. DETAILED DESCRIPTION OF THE INVENTION

[0008] Povidone-iodine (PVPI)-containing mouthwashes are generally manufactured by adding PVPI to water or ethanol, followed by the addition and dissolution of other ingredients such as flavorings and pH adjusters. However, adding PVPI to water or ethanol to achieve a high concentration can result in clumping, and PVPI has low solubility in solvents and solubilizers commonly used in pharmaceutical formulations, such as triacetin, D-sorbitol solution, glycerin, and macrogol 400 (polyethylene glycol), making mouthwashes containing high concentrations of PVPI is not easy. To solve this problem, the inventors of the present invention have dispersed PVPI in propylene glycol. After dissolving, it was discovered that by mixing this with glycerin, ethanol, purified water, etc., a mouthwash containing a high concentration of PVPI could be obtained with a uniform composition without lumps.

[0009] [Gargle medicine and its manufacturing method] The mouthwash of the present invention contains approximately twice the amount of povidone-iodine (PVPI) as conventional products (7%), i.e., a high concentration of povidone-iodine of 10% by mass or more, for example, more than 10% by mass to 20% by mass, particularly 14% by mass to 20% by mass, relative to the total amount of the mouthwash (100% by mass) (hereinafter, povidone-iodine will also be referred to as "PVPI").

[0010] The mouthwash containing povidone-iodine at a high concentration as described above is produced by the following steps: dispersing povidone-iodine (PVPI) in propylene glycol (PG) at a PVPI:PG ratio of 1:2.14 to 4.28 (mass ratio) to obtain a dispersion; and mixing the dispersion with a mixed solvent a1 in which at least one selected from the group consisting of ethanol, glycerin, D-sorbitol solution (70%), saccharin sodium, and l-menthol is dissolved in water; or a mixed solvent a2 in which potassium iodide is further dissolved in the mixed solvent a1. In the present invention, povidone-iodine is first dispersed in propylene glycol, and this dispersion is then combined with a solvent containing glycerin or the like, thereby making it possible to obtain a mouthwash in which povidone-iodine is uniformly dispersed and dissolved without forming lumps.

[0011] An example of a method for producing the mouthwash according to the present invention will be given below, but the method is not particularly limited to this and the mouthwash can be produced. First, povidone-iodine (PVPI) is dispersed in propylene glycol (PG) to obtain a dispersion. This dispersion is mixed with mixed solvent a, which is prepared by dissolving at least one selected from the group consisting of ethanol, glycerin, D-sorbitol solution (70%), saccharin sodium, and l-menthol in water, or optionally mixed with mixed solvent b, which is prepared by dissolving potassium iodide in water, and optionally other additives such as a pH adjuster, to obtain a mouthwash (undiluted solution). Note that in this specification, "mixed solvent a" and "mixed solvent b" are classified for convenience purposes to distinguish whether or not the mixed solvent contains potassium iodide. When at least one selected from the group consisting of ethanol, glycerin, D-sorbitol solution (70%), saccharin sodium, and l-menthol, and potassium iodide are dissolved in water and added in the form of a mixed solvent, a portion of them may be added separately in portions during the mixing of the dispersion and the mixed solvent, and when added in portions, they may be added as is or in a form dissolved in water. Furthermore, other additives can be added as appropriate during the mixing of the dispersion and the mixed solvent, and other additives may also be added as needed in a form dissolved in water or an aqueous solvent, and purified water may also be added at the end to adjust the volume, if necessary.

[0012] <Povidone-iodine> The mouthwash of the present invention contains povidone-iodine (poly[1-(2-oxopyrrolidin-1-yl)ethylene]iodine) as an active ingredient. The mouthwash of the present invention is characterized by containing povidone-iodine at a high concentration of 10% by mass or more, for example, more than 10% by mass to 20% by mass, particularly 14% by mass to 20% by mass, relative to the total amount (100% by mass) of the mouthwash.

[0013] <Propylene glycol> The PVPI-containing mouthwash of the present invention contains propylene glycol, which can function as a solubilizer and dissolution aid for povidone-iodine. In the present invention, as described below, povidone-iodine (PVPI) and propylene glycol (PG) are dispersed in PG so that the mass ratio of PVPI:PG is 1:2.14 to 4.28, and this is combined with a solvent such as glycerin, which will be described below, thereby making it possible to suppress the occurrence of lumps and the like in the resulting formulation. If the mass ratio of PVPI:PG is less than 1:2.14, it is difficult to disperse povidone-iodine, and if the mass ratio exceeds 1:4.28, lumps will form.

[0014] <Saccharin sodium> The PVPI-containing mouthwash of the present invention can contain sodium saccharin. Sodium saccharin is known as a non-carbohydrate synthetic sweetener and can serve as both a sweetener and a flavoring agent in the mouthwash of the present invention. In the preparation of the mouthwash of the present invention, sodium saccharin is usually used in the form of sodium saccharin hydrate when it is dissolved in water to form a mixed solvent or when it is added in portions. The amount of saccharin sodium to be added is not particularly limited, but can be, for example, in the range of 0.05% by mass to 5% by mass relative to the total amount of the mouthwash (100% by mass). This amount can also be applied to the form of saccharin sodium hydrate.

[0015] <l-menthol> The PVPI-containing mouthwash of the present invention may also contain 1-menthol. 1-Menthol has the effect of providing a cooling sensation in the mouth and eliminating bad breath, and also generally serves as a flavoring agent that corrects the flavor of oral medications, making them easier to take. The amount of l-menthol to be added is not particularly limited, but can be, for example, in the range of 0% by mass to 5% by mass relative to the total amount (100% by mass) of the mouthwash.

[0016] <Water-based solvent> The PVPI-containing mouthwash of the present invention can contain, as aqueous solvents, glycerin, ethanol, D-sorbitol solution (70%), and water (purified water). The blending amounts of these aqueous solvents are not particularly limited, but for example, the blending amounts can be in the range of 0% to 60% by mass of glycerin, 0% to 60% by mass of ethanol, 0% to 60% by mass of D-sorbitol solution (70%), and 1% to 60% by mass of water (purified water) relative to the total amount of the mouthwash (100% by mass).

[0017] <Potassium iodide> Iodine (available iodine) hydrolyzes in water and its content decreases, but adding potassium iodide can suppress hydrolysis and prevent the decrease in iodine content. The amount of potassium iodide added is not particularly limited, but can be, for example, in the range of 0% by mass to 5% by mass relative to the total amount of the mouthwash (100% by mass).

[0018] <Other additives> The mouthwash according to the present invention may contain other additives as optional components other than those described above, in addition to the effect (medicinal efficacy) of the mouthwash, as long as the effect of the present invention is not impaired. Representative examples of other additives are listed below, but the present invention is not limited to these examples and various additives commonly used in mouthwashes can be blended in. The types of additives used are not limited to those listed below.

[0019] As the anti-inflammatory agent, for example, azulene sulfonic acid and / or its salt, dipotassium glycyrrhizinate, etc. can be used. As the disinfectant, for example, cetylpyridinium and / or its salts, benzalkonium chloride, benzethonium chloride, etc. can be used. Flavoring agents, such as acesulfame potassium, methyl salicylate, camphor, lemon Oil, fennel oil, eucalyptus oil, cinnamon oil, clove oil, vanillin, flavorings, etc. can be used. As the stabilizer, for example, ascorbic acid, polyvinyl alcohol, macrogol, etc. can be used. Examples of alcohols include monoalcohols such as propyl alcohol, and polyhydric alcohols such as polyethylene glycol and sugar alcohols (mannitol, etc.). As the sugar alcohol, for example, xylitol can be used. As the chelating agent, for example, sodium edetate, calcium disodium edetate, and hydrates thereof can be used. As the surfactant, for example, sodium lauryl sulfate, sucrose fatty acid ester, etc. can be used. Examples of isotonic agents that can be used include inorganic salts such as sodium chloride and magnesium chloride, and polyhydric alcohols such as propylene glycol and D-mannitol. Preservatives that can be used include, for example, parabens, thymol, sorbic acid, and the like. Examples of solubilizing agents that can be used include polyhydric alcohol fatty acid esters, triacetin, sucrose, benzyl alcohol, and polyvinylpyrrolidone. Examples of solubilizing agents that can be used include polyoxyethylene hydrogenated castor oil, polysorbate 60 (polyoxyethylene sorbitan monostearate), polysorbate 80 (polyoxyethylene sorbitan monooleate), and lauromacrogol (polyoxyethylene lauryl ether). Examples of thickening agents that can be used include celluloses such as hydroxyethyl cellulose, hydroxypropyl cellulose, and hypromellose (hydroxypropylmethyl cellulose), carboxyvinyl polymers, carmellose sodium, and gelatin. Examples of pH adjusters include citric acid, lactic acid, phosphoric acid, carbonic acid, salts thereof, and hydrates of these salts. Examples of the salts and hydrates of these salts include sodium citrate hydrate, citric acid hydrate, sodium lactate, sodium hydrogen phosphate, sodium hydrogen phosphate hydrate, and sodium hydrogen carbonate.

[0020] The mouthwash of the present invention contains 10-20% by mass of povidone-iodine relative to its total weight (100% by mass), and also contains povidone-iodine (PVPI) and propylene glycol (PG) in a PVPI:PG ratio of 1:2.14-4.28 (by mass). The amounts of the other ingredients are not particularly limited as long as they are within a range that can achieve the desired effects, and can be, for example, as follows (total weight 100% by mass): The above concentrations are those of the undiluted mouthwash solution, which is usually diluted about 1-250 times before use, but can also be used directly (without dilution) depending on the concentration of the preparation. <Gargle prescription (total amount 100g)> Povidone iodine 10-20g 20-80g propylene glycol Sodium saccharin 0.05~5g l-Menthol 0~5g D-sorbitol solution (70%) 0-60g Glycerin 0-60g Ethanol 0-60g Potassium iodide 0-5g ·Water 1~60g

[0021] More specific examples of the formulation of the mouthwash of the present invention are as follows. [Formulation 1] (total amount 100g) Povidone iodine 14g 30g propylene glycol Sodium saccharin 0.16g 5-30g glycerin Ethanol 0-50g Potassium iodide 0-5g ·Water 1~50g [Formulation 2] (total amount 100g) Povidone iodine 14g Sodium saccharin 0.16g l-Menthol 0.24g 30g propylene glycol 1-30g glycerin Ethanol 10-50g Potassium iodide 0-5g ·Water 1~36g

[0022] The above [Formulation 1] can be, for example, formulation [1-1]. [Prescription 1-1] (total amount 100g) Povidone iodine 14g 30g propylene glycol Sodium saccharin 0.16g 5-20g glycerin Ethanol 10-50g Potassium iodide 0-5g ·Water 5~30g Furthermore, the above [Formulation 2] can be, for example, formulation [2-1]. [Prescription 2-1] (total amount 100g) Povidone iodine 14g Sodium saccharin 0.16g l-Menthol 0.24g 30g propylene glycol 3-20g glycerin 15-50g of ethanol Potassium iodide 0-5g ·Water 5~25g

[0023] The mouthwash of the present invention can be stored in a container made of a conventional resin such as polyethylene (PE), polypropylene (PP), or polyethylene terephthalate (PET), or in a glass container. The shape of the container is not particularly limited. [Example]

[0024] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to these examples.

[0025] [Reference Example 1: Solubility of povidone-iodine (1)] An excess amount of povidone-iodine was added to 5 g of the solvent sample shown in Table 1 below, and ultrasonically treated for 30 minutes. After treatment, the supernatant was obtained by centrifugation, and this was titrated with 0.02 mol / L sodium thiosulfate solution to calculate the amount of available iodine (mg) contained in the supernatant. Based on the amount of available iodine (mg) obtained, the povidone-iodine (PVPI) concentration (%) in each sample was calculated. The results obtained are also shown in Table 1. For reference, for each solvent sample, The maximum dosages of pharmaceutical additives in previous use cases are also shown in Table 1 (showing previous use cases in dental topical and oral preparations, which are classified as mouthwashes).

[0026] [Table 1]

[0027] As shown in Table 1, the concentrations (solubility) of povidone-iodine in water, ethanol, and propylene glycol were high at 30% or more, confirming that povidone-iodine has high solubility.

[0028] [Reference Example 2: Solubility of povidone-iodine (2)] Povidone-iodine (PVPI: 1.4 g) was added to the solvent samples (1 to 6 g) shown in Table 2 below and ultrasonically treated for 30 minutes. After treatment, the appearance of each sample was visually observed and evaluated according to the following criteria. The results are shown in Table 2. <Solubility, Appearance, Evaluation Criteria> A: The entire sample had a brownish-red appearance (PVPI was uniformly dispersed). B: The sample appeared transparent to light brown (PVPI was uniformly dispersed). C: The sample had a brownish appearance, but lumps were observed. D...PVPI distribution not possible

[0029] [Table 2]

[0030] As shown in Table 2, povidone-iodine was uniformly dispersed in triacetin and PEG400, but the sample appearance was transparent to light brown, confirming the low solubility of povidone-iodine.In addition, purified water and ethanol showed a brownish-red appearance, but the formation of lumps was confirmed. On the other hand, with propylene glycol (6g-3g), no clumping was observed, and the tablets had a brownish appearance, confirming high solubility and dispersibility of povidone-iodine.With less than 3g of propylene glycol (2g-1g), clumping was observed, or the liquid volume was too small to disperse povidone-iodine. From the above results, it was confirmed that propylene glycol is particularly preferable as a dissolving agent for povidone-iodine, and that by combining propylene glycol in a mass ratio of at least 2.14 to povidone-iodine, it can be dissolved and dispersed uniformly without the formation of lumps.

[0031] [Production Example 1: Preparation of PVPI-Containing Mouthwash (1): Examination of Blend Amount] Povidone-iodine (PVPI)-containing mouthwashes were prepared according to the following formulation example 1 or formulation example 2. <Formulation example 1> 14 g of povidone-iodine was dispersed in 30 g of propylene glycol (1 part povidone-iodine to 2.14 parts propylene glycol (mass ratio)) to prepare Dispersion 1. 0.16 g of saccharin sodium hydrate was mixed with 0 to 60 g of glycerin, 0 to 60 g of ethanol, and 1 to 60 g of purified water (the amounts of these three components were varied within the ranges of 0 to 60 g or 1 to 60 g), to prepare a mixed solvent. This was then combined with Dispersion 1 to make a total of 100 g, and ultrasonicated for 30 minutes to prepare a mouthwash. <Prescription Example 2> 14 g of povidone-iodine was dispersed in 30 g of propylene glycol to prepare Dispersion Liquid 2. 0.24 g of l-menthol and 0.16 g of sodium saccharin hydrate were combined with 0 to 60 g of glycerin, 0 to 60 g of ethanol, and 1 to 60 g of purified water (the amounts of these three components were varied within the range of 0 to 50 g or 1 to 60 g), to prepare a mixed solvent. This was then combined with Dispersion Liquid 2 to make a total volume of 100 g, and ultrasonicated for 30 minutes to prepare a mouthwash.

[0032] [Table 3]

[0033] The appearance of the mouthwash was visually observed during preparation and after being left to stand for approximately one hour after preparation to check for the presence or absence of clumping, crystal precipitation, or sedimentation. The range of blending amounts of glycerin, ethanol, and purified water was determined in which no clumping, crystal precipitation, or sedimentation was observed. <Prescription Example 1: Results> When 14 g of povidone-iodine, 30 g of propylene glycol, and 0.16 g of sodium saccharin hydrate were combined with 5 to 30 g of glycerin, 0 to 50 g of ethanol, and 1 to 50 g of purified water to make a total of 100 g, no lumps were formed during production, and no crystal precipitation was observed in the resulting mouthwash, confirming that it was a mouthwash with a uniform appearance. <Prescription Example 2: Results> When 14 g of povidone-iodine, 30 g of propylene glycol, 0.16 g of sodium saccharin hydrate, and 0.24 g of l-menthol were combined with 5 to 30 g of glycerin, 20 to 50 g of ethanol, and 1 to 36 g of purified water to make a total of 100 g, no lumps were formed during production, and no crystal precipitation or the like was observed in the resulting mouthwash, confirming that it was a mouthwash with a uniform appearance.

[0034] [Production Examples 2 to 4: Preparation of PVPI-Containing Mouthwash (2)] 14 g of povidone-iodine (PVPI) was dispersed in 30 g of propylene glycol (PG) to obtain a dispersion liquid. According to the blending amounts shown in Table 4, ethanol, glycerin, saccharin sodium hydrate, and l-menthol were dissolved in water to obtain a mixed solvent. The dispersion liquid and the mixed solvent were mixed to prepare PVPI-containing mouthwashes of Production Examples 2 to 4. After preparation, each mouthwash was left to stand for about 1 hour, and then the appearance was visually observed. The results are shown in Table 4.

[0035] [Table 4]

[0036] As shown in Table 4, povidone-iodine and l-menthol precipitated in Production Example 2, and l-menthol precipitated in Production Example 3, but Production Example 4 produced a mouthwash with a uniform composition in which no components precipitated.

[0037] As described above, according to the present invention, it is possible to provide a mouthwash containing povidone-iodine (PVPI) that contains PVPI at a higher concentration than conventional products (7%).

Claims

1. A method for producing a povidone-iodine-containing mouthwash, which contains 10% by mass or more of povidone-iodine relative to the total amount (100% by mass) of the mouthwash, a step of dispersing povidone-iodine (PVPI) in propylene glycol (PG) so that the mass ratio of PVPI to PG is 1:2.14 to 4.28 to obtain a dispersion; the method includes a step of mixing the dispersion with a mixed solvent a1 obtained by dissolving at least one selected from the group consisting of ethanol, glycerin, D-sorbitol solution (70%), saccharin sodium, and l-menthol in water, or a mixed solvent a2 obtained by further dissolving potassium iodide in the mixed solvent a1, How to make mouthwash.

2. A povidone-iodine-containing mouthwash containing the following ingredients (total amount 100g): Povidone iodine 10-20g 20-80g propylene glycol Sodium saccharin 0.05-5g l-menthol 0-5g D-sorbitol liquid (70%) 0-60g Glycerin 0-60g Ethanol 0-60g Potassium iodide 0-5g 1-60g water

3. 3. The povidone-iodine-containing mouthwash of claim 2, containing the following ingredients (total amount 100 g): Povidone iodine 14g 30g propylene glycol Sodium saccharin 0.16g 5-30g glycerin Ethanol 0-50g Potassium iodide 0-5g 1-50g water

4. 3. The povidone-iodine-containing mouthwash of claim 2, containing the following ingredients (total amount 100 g): Povidone iodine 14g 30g propylene glycol Sodium saccharin 0.16g l-menthol 0.24g 1-30g glycerin 10-50g ethanol Potassium iodide 0-5g 1-36g water

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