Packaged hydrous composition

Abstract

Provided is a new means of reducing the microbial contamination of an aqueous composition.　Specifically provided is a packaged aqueous composition obtained by accommodating an aqueous composition that contains a zirconium cyclosilicate in a package.

Description

[Technical Field]

[0001] The present invention relates to a packaged water-containing composition and the like. [Background technology]

[0002] Compositions containing at least water as a solvent (water-containing compositions) are widely used as pharmaceuticals, quasi-drugs, etc. because of their advantages such as being less irritating to living organisms and being able to incorporate various ingredients. However, since it contains water, it is susceptible to contamination by microorganisms. For this reason, a preservative (bactericide) is often added to the water-containing composition to impart a preservative effect. Examples of the preservative include parabens and quaternary ammonium surfactants such as benzalkonium chloride.

[0003] However, it has been pointed out that these preservatives have problems such as cytotoxicity (for example, Non-Patent Document 1), and there is a need to provide new means for reducing microbial contamination of aqueous compositions.

[0004] Meanwhile, sodium zirconium cyclosilicate hydrate, a type of zirconium cyclosilicate, is known as a compound whose effectiveness in treating hyperkalemia has actually been confirmed (Patent Documents 1 and 2), and suspension sachets of sodium zirconium cyclosilicate hydrate (powder formulations) are sold in the United States, Japan, etc. as LOKELMA or LOKELMA (both registered trademarks), a drug indicated for hyperkalemia (Non-Patent Documents 2 and 3). When taking this drug, patients are instructed to empty the entire sachet into a container and suspend the drug in an appropriate amount of water before taking it, but they are also instructed to discard the suspended drug without storing it (Non-Patent Document 4), and it is only distributed and stored in powder form. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Special Publication No. 2014-506556 [Patent Document 2] Special Publication No. 2016-535749 [Non-patent literature]

[0006] [Non-Patent Document 1] New Ophthalmology 8(10):1599~1603, 1991 [Non-patent document 2] LOKELMA® Package Insert, 2018 [Non-patent document 3] "Lokelma Suspension Powder Sachets 5g / Lokelma Suspension Powder Sachets 10g" package insert, March 2020 [Non-patent document 4] "Medicine Guide: Lokelma Suspension Powder Packet 5g," May 2020 Summary of the Invention [Problem to be solved by the invention]

[0007] However, there have been no reports to date on the preservative effect of adding zirconium cyclosilicate to a water-containing composition. An object of the present invention is to provide a new means for reducing microbial contamination of a water-containing composition. [Means for solving the problem]

[0008] The present inventors have conducted extensive research to solve the above-mentioned problems and have found that zirconium cyclosilicates, such as sodium zirconium cyclosilicate hydrate, which are known to be useful in the treatment of hyperkalemia, unexpectedly have excellent antiseptic effects when incorporated into aqueous compositions. They have also found that by incorporating zirconium cyclosilicate into an aqueous composition and then storing the composition in a package (container), microbial contamination of the aqueous composition can be reduced over a long period of time, leading to the completion of the present invention.

[0009] That is, the present invention provides a packaged hydrous composition, in which a hydrous composition containing zirconium cyclosilicate is contained in a package. [Effects of the Invention]

[0010] According to the present invention, a water-containing composition having reduced microbial contamination and good storage stability can be provided. DETAILED DESCRIPTION OF THE INVENTION

[0011] <<Invention of an embodiment relating to a packaged water-containing composition>> As used herein, "zirconium cyclosilicate" refers to a component containing at least zirconium cyclosilicate and one or more cations, and may be a solvate such as a hydrate. Examples of cations include cations of Group 1 elements such as potassium ions, sodium ions, rubidium ions, and cesium ions; cations of Group 2 elements such as calcium ions and magnesium ions; and hydrogen ions, among which one or more can be selected. From the viewpoint of reducing microbial contamination, a cation selected from the group consisting of sodium ions and hydrogen ions is preferred.

[0012] As the zirconium cyclosilicate, from the viewpoint of reducing microbial contamination, one or more selected from the group consisting of sodium zirconium cyclosilicate and solvates thereof are preferred, and sodium zirconium cyclosilicate hydrate (Japanese Adopted Name (JAN); US Adopted Name (USAN) is Sodium zirconium cyclosilicate) is particularly preferred.

[0013] Zirconium cyclosilicate is a component that is poorly soluble in water, and its form is not particularly limited, but examples thereof include powder. The particle size of zirconium cyclosilicate is not particularly limited, but from the viewpoint of improving suspension (dispersion stability) in the water-containing composition and imparting an antiseptic effect throughout the water-containing composition, it is preferably 1 to 200 μm, more preferably 3 to 150 μm, even more preferably 5 to 100 μm, and particularly preferably 10 to 50 μm. The particle size refers to a median size, and can be measured, for example, by a particle size distribution analyzer (specifically, for example, particle size distribution analyzer LS 13 320 (Beckman Coulter)).

[0014] Zirconium cyclosilicate is a known compound and may be produced by a known method, or a commercially available product may be used, such as sodium zirconium cyclosilicate hydrate (trade name: LOKELMA (registered trademark) (AstraZeneca)).

[0015] The content of zirconium cyclosilicate is not particularly limited, but from the viewpoint of reducing microbial contamination, it is preferably 1% by mass or more, more preferably 2% by mass or more, even more preferably 3% by mass or more, and particularly preferably 4% by mass or more, based on the total mass of the hydrous composition, and from the viewpoint of swallowing comfort, etc., it is preferably 65% ​​by mass or less, more preferably 60% by mass or less, even more preferably 55% by mass or less, even more preferably 50% by mass or less, even more preferably 45% by mass or less, even more preferably 40% by mass or less, even more preferably 37% by mass or less, and particularly preferably 35% by mass or less, based on the total mass of the hydrous composition. Specific ranges are preferably 1 to 60% by mass, more preferably 2 to 50% by mass, even more preferably 3 to 40% by mass, and particularly preferably 4 to 35% by mass, based on the total mass of the hydrous composition.

[0016] From the viewpoint of reducing microbial contamination, the mass ratio of (A) water to (B) zirconium cyclosilicate [(A) / (B)] in the aqueous composition is preferably 0.01 or more, more preferably 0.1 or more, even more preferably 0.3 or more, even more preferably 0.5 or more, even more preferably 0.7 or more, even more preferably 1 or more, even more preferably 1.5 or more, and particularly preferably 2 or more, and from the viewpoint of the feeling of administration, etc., it is preferably 50 or less, more preferably 45 or less, even more preferably 30 or less, even more preferably 25 or less, even more preferably 20 or less, even more preferably 10 or less, even more preferably 9 or less, even more preferably 8 or less, even more preferably 7 or less, and particularly preferably 6 or less. Specific ranges are preferably 0.1 or more and 45 or less, more preferably 0.5 or more and 30 or less, more preferably 1 or more and 25 or less, even more preferably 1.5 or more and 20 or less, and particularly preferably 2 or more and 10 or less.

[0017] As used herein, the term "aqueous composition" refers to a composition containing at least water. The term "aqueous composition in a package" refers to a composition that includes a aqueous composition and a package, and the aqueous composition is contained in the package, and is preferably a pharmaceutical preparation. The form of the hydrous composition is not particularly limited, and examples thereof include liquid (such as a suspension) and semi-solid (such as a gel (jelly), ointment, etc.). The properties of the hydrous composition are preferably a viscous liquid or semi-solid, from the viewpoint of improving the suspension (dispersion stability) in the hydrous composition and imparting a preservative effect throughout the hydrous composition. More specifically, a hydrous composition or semi-solid hydrous composition having a shear viscosity of 1 Pa s or more (more preferably 3 to 50 Pa s, particularly preferably 5 to 20 Pa s) when measured at 25°C using a cone-plate rotational viscometer is preferred. A specific example of the cone-and-plate rotational viscometer is the Modular Rheometer MCR301 (Anton Paar).

[0018] Examples of water in the aqueous composition include purified water, water for injection, and sterilized purified water. The water content is not particularly limited, but from the viewpoint of reducing microbial contamination, it is preferably 10% by mass or more, more preferably 25% by mass or more, even more preferably 40% by mass or more, even more preferably 55% by mass or more, even more preferably 60% by mass or more, and particularly preferably 70% by mass or more, based on the total mass of the aqueous composition. It is also preferably 99% by mass or less, more preferably 95% by mass or less, even more preferably 90% by mass or less, even more preferably 85% by mass or less, and particularly preferably 80% by mass or less, based on the total mass of the aqueous composition. A more specific range of 60 to 95% by mass, and particularly preferably 70 to 90% by mass, based on the total mass of the aqueous composition, is preferred.

[0019] The pH value of the aqueous composition measured at 25°C is not particularly limited and is usually 2 to 13, but from the viewpoint of reducing microbial contamination, it is preferably 2.5 to 12, more preferably 3 to 11, and particularly preferably 3 to 10.

[0020] The aqueous composition may also contain one or more active pharmaceutical ingredients other than zirconium cyclosilicate, such as calcium polystyrene sulfonate and sodium polystyrene sulfonate.

[0021] The hydrous composition can be made into various dosage forms according to known methods, for example, as described in the General Provisions for Preparations of the Seventeenth Edition of the Japanese Pharmacopoeia, etc. The dosage form is not particularly limited, and examples thereof include dosage forms described in the Seventeenth Edition of the Japanese Pharmacopoeia, specifically, preparations for oral administration such as oral liquids, elixirs, suspensions, emulsions, lemonades, syrups, and oral jellies; preparations for oral administration such as oral liquids and oral semisolids; and the like. The dosage form of the hydrous composition is preferably a dosage form selected from a suspension and an oral jelly, from the viewpoint of improving the suspendability (dispersion stability) in the hydrous composition and imparting an antiseptic effect throughout the hydrous composition.

[0022] In addition to zirconium cyclosilicate and water, the aqueous composition may contain one or more formulation additives commonly used in the fields of pharmaceuticals, foods, etc., depending on the dosage form, etc. Examples of such formulation additives include suspending agents, polymer gel bases, pH adjusters, sweeteners, flavorings, preservatives, etc. In particular, from the viewpoint of improving the suspension (dispersion stability) in the aqueous composition and imparting a preservative effect throughout the aqueous composition, it is preferable to add at least one formulation additive selected from suspending agents and polymer gel bases to the aqueous composition. Moreover, the water-containing composition preferably does not contain acetic acid.

[0023] Examples of suspending agents include cellulose derivatives such as carmellose sodium, hydroxypropylmethylcellulose (hypromellose), hydroxypropyl cellulose, methylcellulose, and croscarmellose sodium; and natural polymers such as gum arabic, sodium alginate, pregelatinized starch, curdlan, carrageenan, agar, xanthan gum, guar gum, glucomannan, psyllium seed gum, gellan gum, tamarind seed gum, tara gum, starch, locust bean gum, and pectin, and these can be used alone or in combination of two or more. Examples of polymer gel bases include pectin, carrageenan, sodium polyacrylate, agar, gelatin, etc., and these can be used alone or in combination of two or more.

[0024] Examples of pH adjusters include ascorbic acid, magnesium L-aspartate, benzoic acid, sodium benzoate, sodium chloride, dilute hydrochloric acid, calcium citrate, citric acid hydrate, sodium citrate hydrate, sodium dihydrogen citrate, disodium citrate, calcium gluconate hydrate, tartaric acid, sodium tartrate, sorbic acid, sodium bicarbonate, lactic acid, calcium lactate hydrate, anhydrous citric acid, anhydrous sodium citrate, anhydrous sodium monohydrogen phosphate, malic acid, calcium hydrogen phosphate hydrate, sodium hydrogen phosphate hydrate, calcium dihydrogen phosphate hydrate, sodium dihydrogen phosphate, and the like, and these may be used alone or in combination of two or more. Examples of sweeteners include aspartame, liquid sugar, fructose, high fructose liquid sugar, reduced maltose starch syrup, acesulfame potassium, high glucose starch syrup, saccharin, saccharin sodium hydrate, sucralose, refined white sugar, refined honey, sorbitol, sorbitol liquid, simple syrup, white sugar, honey, powdered reduced maltose starch syrup, maltitol, maltitol liquid, starch syrup, isomalt, lactose hydrate, mannitol, and the like, and these can be used alone or in combination of two or more. Examples of flavorings include orange flavor, kiwi fruit flavor, grapefruit flavor, strawberry flavor, cherry flavor, fruit flavor, muscat flavor, raspberry flavor, apple flavor, lemon flavor, caramel flavor, green tea flavor, cocoa flavor, coffee flavor, sugar flavor, honey flavor, vanilla flavor, peppermint flavor, vermouth flavor, mint flavor, maple flavor, and yogurt flavor, and these can be used alone or in combination of two or more. Examples of preservatives include sorbic acid, potassium sorbate, benzoic acid, sodium benzoate, methyl parahydroxybenzoate, butyl parahydroxybenzoate, propyl parahydroxybenzoate, benzalkonium chloride, and benzododecinium bromide, which can be used alone or in combination of two or more.

[0025] Next, the package (container) of the packaged hydrous composition of the present invention will be described. The packaged hydrous composition of the present invention is prevented from invading from the outside by the hydrous composition being contained in a package, and this, combined with the preservative effect of including zirconium cyclosilicate in the hydrous composition, reduces microbial contamination of the hydrous composition. Here, the "package" is not particularly limited in shape, material (raw material), etc., as long as it can accommodate the aqueous composition, and may be appropriately selected depending on the dosage form, etc. Furthermore, the "package" refers to a product used during transportation or storage, and is a concept excluding reactors. The package is preferably a "sealed container" (a container that can prevent solid foreign matter from entering and prevent loss of the contained medicinal product under normal handling, transportation, or storage conditions), an "airtight container" (a container that can prevent solid or liquid foreign matter from entering and prevent loss, efflorescence, deliquescence, or evaporation of the contained medicinal product under normal handling, transportation, or storage conditions), or a "sealed container" (a container that cannot allow gas to enter under normal handling, transportation, or storage conditions), as defined in the General Rules of the Japanese Pharmacopoeia, 17th Edition. From the viewpoint of further preventing the invasion of microorganisms from the outside, the "airtight container" or "sealed container" is preferred.

[0026] The form of the package is not particularly limited and may be appropriately selected depending on the dosage form, intended use, etc. of the hydrous composition. The package may be a regular container or an irregular container (flexible packaging container), and specific examples include bottle packaging, SP (Strip Package) packaging, pillow packaging, stick packaging, and tube packaging. The material (raw material) of the package is not particularly limited, and any material used for packaging water-containing compositions in the fields of medicines, food, etc. can be used as appropriate. Examples of materials for the bottle body used in bottle packaging include glass, plastics (polyester, polyethylene (low density (LDPE), high density (HDPE), etc.), polypropylene, polystyrene, polycarbonate, etc.), and metals (aluminum, etc.). Examples of materials for the stopper and lid include plastics (polyester, polyethylene, polypropylene, polystyrene, polycarbonate, etc.), and metals (aluminum, etc.).

[0027] Examples of packaging materials used for SP packaging, pillow packaging, stick packaging, tube packaging, and the like include biaxially oriented polypropylene (OPP), biaxially oriented polyester (PET), glucose-modified PET (PET-G), biaxially oriented nylon (ONy, PA), cellophane, paper, low-density polyethylene (LDPE), linear low-density polyethylene (L-LDPE), ethylene-vinyl acetate copolymer (EVA), unoriented polypropylene (CPP, IPP), ionomer resin (IO), ethylene-methacrylic acid copolymer (EMAA), polyacrylonitrile (PAN), biaxially oriented polyvinylidene chloride (PVDC), ethylene-vinyl alcohol copolymer resin (EVOH), polyvinyl chloride (PVC), cyclic polyolefin (COC), unoriented nylon (CNy), polycarbonate (PC), polystyrene (PS), and rigid polyvinyl chloride (VSC), as well as metal foils such as aluminum foil (AL). Multilayer structures may also be used in which two or more of these materials are appropriately combined. Examples of such multilayer structures include a laminate of PVC and PVDC (PVC / PVDC; hereinafter, this will be abbreviated as such), PVC / PVDC / PE / PVC, PVC / PVDC / PE / PVDC / PVC, CPP / COC / CPP, PVC / AL, CPP / AL, CPP / CPP / CPP, PET / AL / PE, etc. Methods for forming such multilayer structures include known lamination methods such as extrusion lamination, dry lamination, coextrusion lamination, thermal lamination, wet lamination, non-solvent lamination, and heat lamination.

[0028] In the present invention, the "packaged hydrous composition" refers to a composition that is distributed and transported or stored as such. By incorporating zirconium cyclosilicate into the hydrous composition to impart a preservative effect and by placing the hydrous composition in a package to reduce the intrusion of microorganisms from the outside, it is possible to reduce microbial contamination over a long period of time, and therefore the hydrous composition can be stably distributed in its original state for a long period of time. Furthermore, as described below, the packaged hydrous composition of the present invention contains zirconium cyclosilicate, which is useful for treating hyperkalemia, and can be used, for example, as a pharmaceutical product with the efficacy and effect of treating hyperkalemia. Therefore, the packaged hydrous composition of the present invention may contain instructions for use as a pharmaceutical product (a package insert or instruction manual, specifically including, for example, explanatory matters regarding dosage and administration, efficacy and effects, etc.). In this case, the instructions may be displayed on the surface of the package itself, or may be displayed on a separate piece of paper or the like that is separate from the package and combined with the packaged hydrous composition (for example, the packaged hydrous composition and the paper containing the instructions may be contained in the same container), or the packaged hydrous composition may be further contained in a container and the instructions may be displayed on the surface of the container.

[0029] The packaged hydrous composition of the present invention can be produced by a known method, for example, as described in the Seventeenth Edition of the Japanese Pharmacopoeia, etc. For example, when the hydrous composition is a suspension, it can be produced by adding water and, if necessary, a suspending agent or other additives to zirconium cyclosilicate, suspending the mixture by an appropriate method using a homomixer, homogenizer, colloid mill, or the like, making the whole homogenous, and then packaging it in a stick, etc. Furthermore, when the hydrous composition is an oral jelly, it can be produced by adding water, a polymer gel base, and other additives as necessary to zirconium cyclosilicate, mixing them, pouring them into a fixed-shape container (such as a portion cup), allowing them to gel, and molding them into a specific shape.

[0030] The packaged hydrous composition of the present invention contains zirconium cyclosilicate, which is useful for treating hyperkalemia. Therefore, it can be used as a pharmaceutical containing zirconium cyclosilicate as an active ingredient and with the efficacy and effect of treating hyperkalemia. In this case, the dosage regimen can be, for example, as follows: for an adult, an initial dose of the hydrous composition is administered three times daily for several days (e.g., 2 or 3 days) so that the hydrous composition is administered in an amount equivalent to a single dose of approximately 10 g of zirconium cyclosilicate; thereafter, the hydrous composition is orally administered once daily in an amount equivalent to a single dose of 5 g of zirconium cyclosilicate. The dosage may be increased or decreased depending on the serum potassium level and the patient's condition, but the maximum dosage is preferably set to a maximum dose of 15 g of zirconium cyclosilicate per day. Furthermore, in patients undergoing hemodialysis, it is preferable to orally administer the hydrous composition once daily in an amount equivalent to a single dose of 5 g of zirconium cyclosilicate. The dose may be increased or decreased as appropriate depending on the pre-dialysis serum potassium level after the maximum dialysis interval and the patient's condition, but the maximum dose is preferably set to an amount that results in a single daily administration of 15 g of zirconium cyclosilicate.

[0031] The packaged hydrous composition of the present invention is one in which microbial contamination of the hydrous composition is reduced and has good storage stability. Microorganisms are broadly classified into bacteria and fungi. Examples of bacteria include gram-positive bacteria such as Staphylococcus aureus, and gram-negative bacteria such as Pseudomonas aeruginosa and Escherichia coli. Examples of fungi include Candida albicans. Among these, the hydrous composition of the present invention is particularly effective in reducing fungal contamination.

[0032] <<Invention of an aspect relating to a method for imparting antiseptic effect>> Furthermore, in addition to the above-mentioned packaged hydrous composition, the present invention can also provide the following method for imparting a preservative effect. A method for imparting a preservative effect to a hydrous composition, comprising step A of incorporating zirconium cyclosilicate into the hydrous composition, and step B of containing the hydrous composition in a package. Step B may be carried out after step A, or step A may be carried out after step B, as long as the hydrous composition containing zirconium cyclosilicate is contained in a package. In the method for imparting a preservative effect of the present invention, the preservative effect is judged to be effective if the preservative power of the subject being evaluated is superior to that of a composition not containing zirconium cyclosilicate, and the degree of the effect is not important.

[0033] The meaning of each term in the method for imparting a preservative effect, the amount of each component to be blended, etc. are the same as those explained in the above <<Invention of an embodiment relating to a packaged hydrous composition>>.

[0034] The present specification discloses the following embodiments, for example, but is not limited to these.

[0035] [1-1] A packaged hydrous composition, in which a hydrous composition containing zirconium cyclosilicate is contained in a package. [1-2] The packaged hydrous composition according to [1-1], wherein the zirconium cyclosilicate is preferably one or more selected from the group consisting of sodium zirconium cyclosilicate and solvates thereof, and more preferably sodium zirconium cyclosilicate hydrate. [1-3] The packaged hydrous composition according to [1-1] or [1-2], wherein the content of the zirconium cyclosilicate is preferably 1% by mass or more, more preferably 2% by mass or more, even more preferably 3% by mass or more, and particularly preferably 4% by mass or more, relative to the total mass of the hydrous composition, and is preferably 65% ​​by mass or less, more preferably 60% by mass or less, even more preferably 55% by mass or less, even more preferably 50% by mass or less, even more preferably 45% by mass or less, even more preferably 40% by mass or less, even more preferably 37% by mass or less, and particularly preferably 35% by mass or less, relative to the total mass of the hydrous composition. [1-4] The content of water relative to the total mass of the aqueous composition: The packaged hydrous composition according to any one of [1-1] to [1-3] is preferably 10% by mass or more, more preferably 25% by mass or more, even more preferably 40% by mass or more, even more preferably 55% by mass or more, even more preferably 60% by mass or more, and particularly preferably 70% by mass or more, and is preferably 99% by mass or less, more preferably 95% by mass or less, even more preferably 90% by mass or less, even more preferably 85% by mass or less, and particularly preferably 80% by mass or less, based on the total mass of the hydrous composition.

[0036] [1-5] The packaged hydrous composition according to any one of [1-1] to [1-4], wherein the package is preferably a sealed container, an airtight container or a sealed container, more preferably an airtight container or a sealed container. [1-6] The packaged hydrous composition according to any one of [1-1] to [1-5], wherein the dosage form of the hydrous composition is preferably selected from a suspension and an oral jelly. [1-7] The packaged hydrous composition according to any one of [1-1] to [1-6], which is a pharmaceutical preparation. [1-8] The packaged hydrous composition according to any one of [1-1] to [1-7], which is a pharmaceutical product having the efficacy and effect of treating hyperkalemia. [1-9] The packaged hydrous composition according to any one of [1-1] to [1-8], which includes instructions for use as a medicine.

[0037] [2-1] A method for imparting a preservative effect to a water-containing composition, comprising: step A of incorporating zirconium cyclosilicate into the water-containing composition; and step B of packaging the water-containing composition in a package. [2-2] The method according to [2-1], wherein the zirconium cyclosilicate is preferably at least one selected from the group consisting of sodium zirconium cyclosilicate and solvates thereof, and more preferably sodium zirconium cyclosilicate hydrate. [2-3] The method according to [2-1] or [2-2], wherein the content of the zirconium cyclosilicate is, relative to the total mass of the hydrous composition, preferably 1% by mass or more, more preferably 2% by mass or more, even more preferably 3% by mass or more, particularly preferably 4% by mass or more, and is preferably 65% ​​by mass or less, more preferably 60% by mass or less, even more preferably 55% by mass or less, even more preferably 50% by mass or less, even more preferably 45% by mass or less, even more preferably 40% by mass or less, even more preferably 37% by mass or less, particularly preferably 35% by mass or less.

[0038] [2-4] The method according to any one of [2-1] to [2-3], wherein the package is preferably a sealed container, an airtight container or a sealed container, more preferably an airtight container or a sealed container. [2-5] The method according to any one of [2-1] to [2-4], wherein the dosage form of the hydrous composition is preferably selected from a suspension and an oral jelly. [2-6] The method according to any one of [2-1] to [2-5], wherein the pharmaceutical preparation is a pharmaceutical preparation. [Example]

[0039] The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to these examples in any way.

[0040] [Test Example 1] Confirmation of the antiseptic effect of sodium zirconium cyclosilicate hydrate In order to confirm whether or not zirconium cyclosilicate sodium hydrate has an antiseptic effect against microorganisms (bacteria and fungi), the following test was carried out using Staphylococcus aureus as the bacterium and Candida albicans as the fungus.

[0041] <Confirmation of antiseptic effect against Staphylococcus aureus> Staphylococcus aureus subsp. aureus NBRC 13276 strain was inoculated onto soybean casein digest agar medium (Nissui Pharmaceutical Co., Ltd.) and cultured at 30-35°C for 18-24 hours. After culture, the cells were suspended in saline and diluted with saline to a concentration of 100-10,000 CFU / mL to obtain a test bacterial solution.

[0042] 15 g of sodium zirconium cyclosilicate hydrate (LOKELMA (registered trademark), lot number W0200018A: AstraZeneca) was suspended in 35 mL of sterilized purified water to obtain a sample suspension.

[0043] 5 mL of the sample suspension was mixed with 0.05 mL of the test bacteria solution to prepare a test sample (a control sample was prepared by mixing 5 mL of sterilized purified water with 0.05 mL of the test bacteria solution). The obtained test sample and control sample were each placed in a 14 mL polystyrene round tube and stored at 20 to 25°C for 1 hour under light-shielded conditions.

[0044] The viable bacterial counts of the test samples and control samples were measured immediately after sample preparation and after 1 hour of storage using the pour plate method as follows. Specifically, 1 mL of each sample immediately after preparation and after 1 hour of storage was dispensed into a Petri dish, mixed with soybean casein digest agar medium that had been warmed to approximately 45°C, and cultured at 30-35°C for 3 days. After the incubation, the number of colonies formed was counted. The same incubation was performed twice, and the average number of colonies counted from the two Petri dishes was taken as the "viable cell count."

[0045] From the obtained viable cell count, the survival rate (%) after 1 hour of storage was calculated using the following formula.

[0046] Viability (%) = (number of viable bacteria in each sample after 1 hour storage / number of viable bacteria in each sample immediately after preparation) × 100

[0047] <Confirmation of antiseptic effect against Candida> Candida albicans NBRC 1594 strain was inoculated onto Sabouraud-dextrose agar medium (Nissui Pharmaceutical Co., Ltd.) and cultured for 44 to 52 hours at 20 to 25°C. After culture, the cells were suspended in saline and diluted with saline to a concentration of 100 to 10,000 CFU / mL to obtain a test bacterial solution. The obtained test bacterial solution was used in the same manner as in the test for Staphylococcus aureus described above (except that in the pour plate agar method, Sabouraud glucose agar medium was used instead of soybean casein digest agar medium, and the incubation conditions were 20-25°C for 3 days), and the survival rate (%) was calculated in the same manner. The results are shown in Table 1.

[0048] [Table 1]

[0049] The results shown in Table 1 reveal that the survival rates of both Staphylococcus aureus and Candida decreased after just one hour of storage in purified water containing suspended sodium zirconium cyclosilicate. From the above test results, it became clear that by incorporating zirconium cyclosilicate into a water-containing composition and storing it in a package, it is possible to impart a preservative effect against bacteria and fungi, and to reduce microbial contamination of the water-containing composition.

[0050] [Manufacturing Examples 1 to 9] A hydrous composition (oral jelly) containing the ingredients and amounts shown in Table 2 is prepared by a conventional method. The prepared hydrous composition is placed in a polypropylene portion cup container (heat-sealed with a polyethylene-laminated aluminum foil film) in an amount of 100 g per container, thereby producing the packaged hydrous compositions of Production Examples 1 to 9.

[0051] [Table 2]

[0052] [Manufacturing Examples 10-18] A water-containing composition (suspension) containing the ingredients and amounts shown in Table 3 is prepared by a conventional method. The prepared water-containing composition is placed in a polyethylene-laminated aluminum foil stick packaging container in an amount of 100 mL per package, thereby producing the packaged water-containing compositions of Production Examples 10 to 18.

[0053] [Table 3] [Industrial Applicability]

[0054] According to the present invention, a packaged water-containing composition with reduced microbial contamination can be provided, which can be used in, for example, the pharmaceutical industry.

Claims

1. The packaged hydrous composition comprises a hydrous composition containing zirconium cyclosilicate, the hydrous composition being contained in a package, and the content of the zirconium cyclosilicate being 10 to 60 mass % relative to the total mass of the hydrous composition.

2. 2. The packaged hydrous composition according to claim 1, which is a pharmaceutical product having the efficacy and effect of treating hyperkalemia.

3. 3. The packaged hydrous composition according to claim 1, further comprising instructions for use as a medicine.

4. The packaged hydrous composition according to any one of claims 1 to 3, wherein the zirconium cyclosilicate is at least one selected from the group consisting of sodium zirconium cyclosilicate and solvates thereof.

5. The packaged hydrous composition according to any one of claims 1 to 3, wherein the zirconium cyclosilicate is sodium zirconium cyclosilicate hydrate.

6. The packaged hydrous composition according to any one of claims 1 to 5, wherein the package is an airtight container or a sealed container.

7. 7. The packaged hydrous composition according to claim 1, wherein the hydrous composition is in a dosage form selected from the group consisting of a suspension and an oral jelly.

8. A method for imparting a preservative effect to a water-containing composition, comprising the steps of incorporating zirconium cyclosilicate into the water-containing composition, and placing the water-containing composition in a package.

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