JP5089956B2 - Liquid medicine product for internal use - Google Patents

Description

  The present invention relates to a liquid preparation for internal use in which a paper container is filled with an aqueous liquid composition containing vitamins and / or derivatives thereof.

Conventionally, there is a paper container such as a paper pack as a container used to store a liquid. As this paper container, what shape | molded the lamination sheet by which the thermoadhesive resin layer was laminated | stacked on the base material layer made from paper is mainly used. One type of such a paper container has an aluminum layer such as an aluminum foil. Paper containers having an aluminum layer are excellent in light-shielding properties, airtightness, and the like, and are used for accommodating various liquids (see, for example, Patent Documents 1 and 2).
However, depending on the components contained in the contents of the paper container having an aluminum layer, when the contents are accommodated, corrosion occurs from the penetration of the contents into the aluminum layer, and as a result, delamination ( There is a problem that delamination occurs. In order to deal with such a problem, for example, Patent Documents 3 to 4 propose providing a specific resin layer inside the container rather than the aluminum layer.

On the other hand, various vitamins are generally added to an aqueous liquid composition for internal use, but some vitamins have unstable components when the pH is high. In order to improve the stability of such vitamins, an acid is added to the aqueous liquid composition to lower its pH (see, for example, Patent Documents 5 to 7).
Japanese Patent Laid-Open No. 9-234043 JP 2006-136318 A Japanese Patent Laid-Open No. 8-66987 JP-A-9-327888 JP-A-10-67659 JP-A-10-67660 JP 2005-104960 A

The low pH aqueous liquid composition as described above, particularly an aqueous liquid composition having a pH of 3.5 or less, is usually contained in a brown glass bottle, and is difficult to contain, for example, in a paper container having the above-described aluminum layer. It is.
This is because, when a liquid having a pH of 3.5 or less is contained in a paper container having an aluminum layer, the acid concentration becomes high, and delamination as described above occurs in each layer of the laminated sheet of the container, particularly in the aluminum layer part. This is because it will occur. Therefore, the pH of the liquid stored in such a paper container is normally set to a relatively high pH of 3.5 or more. Therefore, until now, it has been difficult to stably mix vitamins in an aqueous liquid composition housed in a paper container having an aluminum layer.
An object of the present invention is to provide a liquid preparation for internal use in which the occurrence of delamination in a paper container containing an aqueous liquid composition containing a vitamin is suppressed and the stability of the vitamin is improved.

As a result of intensive studies, the present inventors have found that the above problem can be solved by using a specific acid in the aqueous liquid composition, and have completed the present invention.
That is, the present invention relates to thiamine , thiamine nitrate, thiamine hydrochloride, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate ester salt, dicetiamine hydrochloride, fursultiamine hydrochloride, octothiamine, chicotiamine, bisbutiamine, bisbenchamine, fullsulamine. A vitamin and / or its at least one selected from the group consisting of thiamine, prosultiamine, benfotiamine, nicotinamide, ascorbic acid, ascorbate, ascorbate and L-ascorbic acid-2-glucoside A derivative (A);
Or glucuronic acid, or glucuronic acid, lactic acid, butyric acid, malic acid, aspartic acid, glutamic acid, adipic acid, gluconic acid, tartaric acid, succinic acid, at least one member selected from the group consisting of maleic acid and fumaric acid contains an organic acid (B) is a combination of, and the aqueous liquid composition is pH3.5 or less, at least a paper layer, an aluminum layer and the resin layer is Do Ri innermost from said laminated sheet formed by laminating in this order A liquid preparation for internal use, which is filled in a paper container which is a resin layer .

  ADVANTAGE OF THE INVENTION By this invention, generation | occurrence | production of the delamination in the paper container which accommodates the aqueous liquid composition containing a vitamin can be suppressed, and the liquid preparation for internal use which the stability of the said vitamin improved can be provided.

<Aqueous liquid composition>
The vitamin and / or its derivative (A) (hereinafter sometimes referred to as the component (A)) is not particularly limited and is appropriately selected from those commonly used for liquids for internal use depending on the purpose. can do.
Examples of the component (A) include vitamin A or a derivative thereof, vitamin B or a derivative thereof (vitamin B1 such as thiamine nitrate, vitamin B2 such as riboflavin sodium phosphate, vitamin B6 such as pyridoxine hydrochloride, vitamin B12, and nicotinamide. And vitamin B5 such as calcium pantothenate), vitamin C or a derivative thereof (ascorbic acid etc.), vitamin D or a derivative thereof, vitamin E or a derivative thereof (tocopherol, tocopherol acetate, etc.).
In the present invention, as the component (A), at least one selected from the group consisting of thiamine and derivatives thereof, nicotinamide, and ascorbic acid and derivatives thereof is particularly preferably used. These vitamins are highly stable vitamins under acidic conditions. Therefore, these vitamins show high stability in the aqueous liquid composition of the present invention having a pH of 3.5 or less.
Thiamine derivatives include thiamine nitrate, thiamine hydrochloride, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate ester salt, dicetiamine hydrochloride, fursultiamine hydrochloride, octothiamine, chicotiamine, bisbutiamine, bisbenchamine, fursultiamine, Examples include prosultiamine and benfotiamine.
Ascorbic acid derivatives include ascorbates such as sodium L-ascorbate and calcium L-ascorbate; ascorbic acid esters such as L-ascorbic acid stearate and L-ascorbic acid palmitate; L-ascorbic acid- Examples include 2-glucoside.

(A) A component may be used individually by 1 type and may use 2 or more types together.
In the aqueous liquid composition, the blending amount of the component (A) is not particularly limited, and may be appropriately determined in consideration of the effective amount or the like according to the type of vitamin or derivative thereof used.
For example, when thiamine or a derivative thereof or nicotinamide is used as the component (A), 1 to 1000 mg is preferable in 100 mL of the aqueous liquid composition, and 10 to 500 mg is more preferable. The effect by mix | blending the said vitamin is fully acquired as it is 1 mg / 100 mL or more, and component stability, the taste of an aqueous liquid composition, etc. are favorable in it being 1000 mg / 100 mL or less.
Moreover, when using ascorbic acid or its derivative as (A) component, 1-3000 mg is preferable in 100 mL of aqueous liquid compositions, and 100-1000 mg is more preferable. The effect by mix | blending the said vitamin is fully acquired as it is 1 mg / 100 mL or more, and component stability, the taste of an aqueous liquid composition, etc. are favorable in it being 1000 mg / 100 mL or less.
(A) A component may be used individually by 1 type and may use 2 or more types together.

The aqueous liquid composition comprises the component (A) and (B) glucuronic acid, lactic acid, butyric acid, malic acid, aspartic acid, glutamic acid, adipic acid, gluconic acid, tartaric acid, succinic acid, maleic acid and fumaric acid At least one organic acid (B) selected from the following (hereinafter also referred to as component (B)).
By containing the component (B) in the aqueous liquid composition, it is possible to improve the stability of the component (A) while suppressing the occurrence of delamination in the container containing the aqueous liquid composition. Moreover, the taste of an aqueous liquid composition is also improved by containing (B) component.
(B) A component may be used individually by 1 type and may use 2 or more types together.
The component (B) preferably contains at least glucuronic acid because it is excellent in the effects of the present invention.
At this time, as component (B), glucuronic acid may be used alone, or component (B) other than glucuronic acid may be used in combination. As the component (B) used in combination with glucuronic acid, butyric acid is preferable.

In the aqueous liquid composition, the blending amount of the component (B) is preferably 50 mg or more, more preferably 100 mg or more, more preferably 300 mg or more in 100 mL of the aqueous liquid composition in consideration of the effect of blending the component (B). Further preferred.
There is no restriction | limiting in particular as an upper limit of the compounding quantity of (B) component. Considering the taste and the like of the aqueous liquid composition, it is preferably 10,000 mg or less, more preferably 5000 mg or less, and further preferably 2000 mg or less in 100 mL of the aqueous liquid composition.

In the present invention, the aqueous liquid composition contains an organic acid other than the component (B) and / or an inorganic acid (C) (hereinafter sometimes referred to as the component (C)) for pH adjustment. Also good.
The organic acid in the component (C) is not particularly limited as long as it does not correspond to the component (B). For example, those that have been used as a pH adjuster so far can be used, such as citric acid and sodium citrate. Glycine, acetic acid, glacial acetic acid and the like.
Examples of the inorganic acid include hydrochloric acid and boric acid.
As the component (C), acetic acid and / or hydrochloric acid is preferable.

(C) A component may be used individually by 1 type and may use 2 or more types together.
In the aqueous liquid composition, the blending amount of the component (C) is not particularly limited. For example, the amount capable of setting the pH of the aqueous liquid composition to a desired value of 3.5 or less together with the component (B). If it is.
In the present invention, in particular, when acetic acid is used as the component (C), the amount of acetic acid is preferably 100 mg or less, more preferably 60 mg or less in 100 mL of the aqueous liquid composition. If the amount of acetic acid exceeds 100 mg / 100 mL, delamination may occur in the container containing the aqueous liquid composition.
Moreover, when using hydrochloric acid as (C) component, it is preferable that the compounding quantity of the said hydrochloric acid shall be 500 mg or less in 100 mL of aqueous liquid compositions, and it is more preferable to set it as 300 mg or less. If the amount of hydrochloric acid exceeds 500 mg / 100 mL, the flavor of the aqueous liquid composition may be deteriorated.

The aqueous liquid composition may contain optional components other than those described above as long as the effects of the present invention are not impaired. Examples of the optional component include various physiologically active ingredients, sweeteners, pH adjusters (excluding the components (B) and (C)), thickeners, solubilizers, preservatives (preservatives). , Stabilizers, fruit juices, fragrances, pigments and the like. The addition amount of these optional components can be blended in a normal amount as long as the effects of the present invention are not hindered.
Examples of the physiologically active ingredient include herbal medicines such as carrots, guarana, toki and peony or extracts thereof, royal jelly, caffeine, carnitine chloride, taurine, capsaicin and the like.

  The sweetener is not particularly limited and may be appropriately selected depending on the intended purpose. For example, sucrose, liquid sugar, fructose, fructose glucose liquid, glucose fructose liquid sugar, reduced maltose water candy, brown sugar, high fructose Liquid sugar, glucose, powdered reduced maltose water candy, water candy, high glucose water candy, lactose, sucrose, purified sucrose, purified sucrose spherical granules, honey, purified honey, simple syrup, erythritol, xylitol, D-sorbitol, D-sorbitol Solution, maltitol, maltitol solution, maltose, D-mannitol, aspartame, acesulfame potassium, amacha extract, licorice extract, saccharin, sodium saccharin, sucralose, stevia extract, neotame, thaumatin, glycine, glycerin, dipotassium glycyrrhizinate , Disodium glycyrrhizinate Sodium glycyrrhizinate tribasic, monoammonium glycyrrhizinate, licorice, and the like. Said sweetener can be used individually by 1 type or in combination of 2 or more types.

  The pH adjuster is not particularly limited as long as it is other than the component (B) and the component (C), and can be appropriately selected according to the purpose. For example, glucono-δ-lactone, sodium hydroxide, water Examples include potassium oxide, magnesium hydroxide, calcium gluconate, calcium lactate, monosodium fumarate, sodium hydrogen carbonate and the like.

  The thickener is not particularly limited and may be appropriately selected depending on the intended purpose. For example, natural water-soluble polymers such as carrageenan, gellan gum, pullulan, and gum arabic; polyvinyl alcohol, polyvinyl pyrrolidone, methyl cellulose, carboxymethyl cellulose, Examples include synthetic water-soluble polymers such as hydroxypropylcellulose. By containing a thickener, the stability of each component in the liquid is improved.

  Examples of the solubilizer include surfactants such as polyoxyethylene hydrogenated castor oil and sucrose fatty acid ester, lower alcohols such as polyhydric alcohol and ethanol, and the like.

  The preservative (preservative) is not particularly limited and may be appropriately selected depending on the intended purpose. For example, benzoic acid, sodium benzoate, ethanol, sodium edetate, dry sodium sulfite, agar, dl-camphor, Citric acid, sodium citrate, glycerin, salicylic acid, sodium salicylate, phenyl salicylate, dibutylhydroxytoluene, D-sorbitol, sorbic acid, potassium sorbate, sodium dehydroacetate, sucrose, honey, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, Examples include ethyl paraoxybenzoate, butyl paraoxybenzoate, propyl paraoxybenzoate, methyl paraoxybenzoate, propylene glycol, 1-menthol, and eucalyptus oil. Said preservative can be used individually by 1 type or in combination of 2 or more types.

  There is no restriction | limiting in particular as said stabilizer, According to the objective, it can select suitably, For example, adipic acid, L-aspartic acid, sodium L-aspartate, aminoethylsulfonic acid, DL-alanine, bisulfite Sodium, sodium sulfite, L-arginine, sodium alginate, propylene glycol alginate, albumin, benzoic acid, sodium benzoate, sulfur, inositol, ethanol, disodium calcium edetate, sodium edetate, erythorbic acid, sodium ersorbate, calcium chloride , Sodium chloride, magnesium chloride, cysteine hydrochloride, cacao butter, fructose, carboxyvinyl polymer, carmellose calcium, carmellose sodium, hydrous silicon dioxide, dry sodium sulfite, dry water Aluminum fluoride gel, dry aluminum hydroxide gel, dry sodium carbonate, xanthan gum, xylitol, calcium citrate, glycerin, glyceryl fatty acid ester, disodium glycyrrhizinate, light anhydrous silicic acid, crystalline cellulose, sodium acetate, sodium salicylate, phenyl salicylate, β-cyclodextrin, dibutylhydroxytoluene, sucrose fatty acid ester, calcium hydroxide, purified gelatin, purified soybean lecithin, purified sucrose, sorbitan sesquioleate, cetanol, gelatin, sorbitan fatty acid ester, D-sorbitol, D-sorbitol solution, Soybean oil unsaponifiable matter, dextran, lactose, concentrated glycerin, sucrose, ethyl paraoxybenzoate, butyl paraoxybenzoate, methyl paraoxybenzoate, microcrystals Cellulose, hydroxypropylcellulose, sodium pyrosulfite, butylhydroxyanisole, glucose, sodium fumarate, propylene glycol, bentonite, propyl gallate, partially neutralized polyacrylic acid, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxy Propylene glycol, polysorbate, polyvinyl pyrrolidone, polyvinyl alcohol, polyvinyl alcohol / dibutyl ether mixture, macrogol, maltose, D-mannitol, anhydrous sodium pyrophosphate, sodium metaphosphate, methylcellulose, l-menthol, aluminum monostearate, monostearic acid Examples include glycerin, medicinal charcoal, sodium lauryl sulfate, and egg white albumin. Said stabilizer can be used individually by 1 type or in combination of 2 or more types.

In the present invention, the pH of the aqueous liquid composition (pH at 25 ° C.) is 3.5 or less, preferably 3.2 or less, and more preferably 3.0 or less. By being under such an acidic region, the stability of the component (A) in the aqueous liquid composition is improved.
The lower limit of the pH of the aqueous liquid composition is not particularly limited, but is preferably 2.0 or more because the taste of the aqueous liquid composition is improved, preferably 2.3 or more, more preferably 2.5 or more. Further preferred.

  There is no restriction | limiting in particular in the preparation method of an aqueous liquid composition, A well-known method can be used suitably. For example, it can be manufactured according to the section of the Japanese Pharmacopoeia General Formulation “Liquid”, filtered and sterilized.

<Paper container>
The paper container used in the present invention comprises a laminated sheet having at least a paper layer, an aluminum layer, and a resin layer, and is laminated in the order of paper layer / aluminum layer / resin layer (innermost layer) in order from the outside of the container. Is. Since the paper container has at least an aluminum layer, it has excellent light shielding properties. This improves the stability of the vitamin in the aqueous liquid composition.
The paper container used in the present invention may further be provided with a resin coating layer on the outside of the paper layer depending on the purpose, and between the paper layer / aluminum layer and between the aluminum layer / resin layer. Arbitrary layers such as an adhesive layer, an adhesive resin layer, an anchor coating agent layer, and a heat resistant resin layer may be provided.

There is no restriction | limiting in particular as a material which comprises a paper layer, The paper base material generally used for the paper container may be sufficient. That is, considering that the paper base material is processed into a liquid container such as a beverage and used, the laminated sheet is provided with moldability, bending resistance, rigidity, etc. that can be used as a container. Is preferred.
Specific examples of preferred paper base materials include, for example, highly sized bleached or unbleached paper base materials having excellent resistance to water absorption, penetration, and bleeding, pure white roll paper, kraft paper, paperboard, and processing. For example, paper.
The basis weight of the paper substrate is preferably ^{80~600g / m 2, 100~450g / m} 2 is more preferable.

The resin layer is made of a resin that can be melted and fused by heat. Examples of the resin include polyethylene such as low density polyethylene, medium density polyethylene, high density polyethylene, and linear low density polyethylene, polypropylene, ethylene-vinyl acetate copolymer, ionomer resin, ethylene-acrylic acid copolymer, and ethylene. -Ethylene-polymer such as ethyl acrylate copolymer, ethylene-methacrylic acid copolymer, ethylene-propylene copolymer, methylpentene polymer, polybutene polymer, ethylene-acrylic acid copolymer or ethylene-methacrylic acid copolymer. Examples thereof include polyolefin resins such as acid-modified polyolefin resins obtained by modifying saturated carboxylic acid copolymers; polyvinyl acetate resins; poly (meth) acrylic resins; thermoplastic resins such as polyvinyl chloride resins. Among these, polyolefin resins are preferable, and polyethylene and / or polypropylene are more preferable.
The innermost layer of the paper container used in the present invention is a resin layer. As the innermost resin layer, a film composed of the above thermoplastic resin is preferable, a polyolefin resin film is preferable, and a polyethylene film and a polypropylene film are excellent in terms of workability (resistance to bending processing, etc.). More preferred.
Although the thickness per layer of the resin layer is not particularly limited, for example, in the case of the resin layer of the container innermost layer, 1 to 50 μm is preferable, and 5 to 300 μm is more preferable.

As the aluminum layer, for example, an aluminum foil, a resin film (for example, one made of a resin mentioned as a resin constituting the thermoplastic resin layer or a heat-resistant resin layer described later) by a normal method such as vacuum deposition, etc. An aluminum vapor-deposited film formed by vapor deposition may be mentioned.
In the laminated sheet, it is preferable that at least the aluminum layer is provided on the side closer to the container inside than the paper layer.
1-50 micrometers is preferable and, as for the thickness of an aluminum layer, 5-30 micrometers is more preferable.

In addition to the above, the laminated sheet may have any layer generally used for paper containers.
Examples of such an optional layer include a coating layer, an adhesive layer, an adhesive resin layer, an anchor coat agent layer, and a heat resistant resin layer.
For example, by providing one or more adhesive layers, adhesive resin layers, and anchor coat agent layers between the innermost resin layer and the aluminum layer inside the container of the laminated sheet, between the aluminum layer and the innermost resin. This is preferable because the adhesion is improved and delamination is less likely to occur. For example, when the innermost resin layer is a polyethylene film or a polypropylene film, it is more preferable to include at least a polyolefin adhesive layer such as polyethylene or polypropylene, or an adhesive resin layer.
Also, by providing a heat-resistant resin layer, when hot air or the like is blown onto the surface of the laminated sheet to melt the heat-adhesive resin layer to form a paper container, the heat resistance of the hot air is improved. It is possible to prevent the occurrence of defects (pinholes, etc.).

As the coating layer, polyethylene such as low density polyethylene, medium density polyethylene, high density polyethylene, linear low density polyethylene, polypropylene, ethylene-vinyl acetate copolymer, ionomer resin, ethylene-acrylic acid copolymer, ethylene-acrylic Ethylene-unsaturated carboxylic acid such as ethyl acid copolymer, ethylene-methacrylic acid copolymer, ethylene-propylene copolymer, methylpentene polymer, polybutene polymer, ethylene-acrylic acid copolymer or ethylene-methacrylic acid copolymer Examples thereof include polyolefin resins such as acid-modified polyolefin resins obtained by modifying acid copolymers; polyvinyl acetate resins; poly (meth) acrylic resins; thermoplastic resin films such as polyvinyl chloride resins.
The thickness of the coating layer is preferably 5 to 300 μm, more preferably 10 to 100 μm.

Adhesive layers and adhesive resin layers (hereinafter, these may be collectively referred to as adhesive layers) include polyolefin-based, polyurethane-based, polyacrylic-based, polyester-based, epoxy-based, polyvinyl acetate-based, etc. Can be used.
Examples of the anchor coating agent layer include urethane, polyethyleneimine, polybutadiene, and organic titanium.

Examples of the resin constituting the heat-resistant resin layer include 6 nylon, 66 nylon, 610 nylon, 612 nylon, 11 nylon, 12 nylon, polyamide by condensation of metaxylenediamine and dibasic acid, and other polyamide-based resins, Examples thereof include polycarbonate resins, polyester resins such as polyethylene terephthalate (PET), polybutylene terephthalate, ethylene-vinyl alcohol copolymers, and other heat resistant resins.
Such a heat-resistant resin layer may be, for example, a coating film formed on the surface of another layer using a composition containing the above resin, and uses a film or sheet made of the resin. May be.
5-100 micrometers is preferable and, as for the thickness of a heat resistant resin layer, 10-50 micrometers is more preferable.

As a specific example of the layer configuration of the laminated sheet, for example, in order from the outside of the container,
Coating layer / paper layer / adhesive layer / aluminum layer / adhesive layer / resin layer;
Coating layer / paper layer / adhesive layer / anchor coat agent layer / aluminum layer / anchor coat agent layer / adhesive layer / resin layer;
-Coating layer / paper layer / adhesive layer / aluminum layer / adhesive layer / heat-resistant resin layer / resin layer and the like. Such a paper container is preferable because it has high adhesion between layers and hardly causes delamination.

  Laminate sheets can be obtained by the usual laminating method, for example, the glue lamination method (wet lamination, dry lamination, hot melt lamination) in which each layer is laminated via an adhesive, or the extrusion lamination method in which molten resin is extruded and laminated. Etc. can be appropriately selected and used.

An ink layer by printing may be formed on the paper container made of the laminated sheet as described above. The position where the ink layer is formed may be a position that can be visually recognized from the outside. For example, the ink layer may be formed on the surface of the paper layer on the outside of the container, and the thermal adhesive resin layer and / or the outer side of the paper layer. When the heat resistant resin layer is provided, it may be formed on the surface thereof.
The method for forming the ink layer is not particularly limited, and for example, methods generally used for printing on paper containers such as flexographic printing, gravure printing, and offset printing can be used.

The shape of the paper container is not particularly limited, and may be the same shape as a commonly used paper container. FIG. 1 shows an example of the shape of a paper container used in the present invention.
The liquid medicine product for internal use in which the aqueous liquid composition is contained in a rectangular parallelepiped paper container such as the paper container 11 shown in FIG. 1 is not particularly limited. For example, a predetermined laminated sheet is bent and both ends thereof are thermally bonded. The heat-resistant resin layers are fused together to form a cylindrical shape, and the opening at the lower end is sealed by heat-sealing to obtain a paper container having an open top, and a predetermined aqueous liquid is contained in the paper container. It can be produced by filling the composition and sealing the opening at the upper end of the paper container by heat sealing.
Examples of the container used in the present invention are described in JP-A No. 2000-309334, JP-A No. 11-70993, JP-A No. 2006-256293, JP-A No. 8-66987, JP-A No. 2005-53495, JP-A No. 2002-200697, and the like. A container etc. can be used. Moreover, as what is marketed, "Tetra brick aseptic (TBA)" (brand name. Nippon Tetra Pak Co., Ltd. product) etc. can be used, for example.

EXAMPLES Next, although an Example is shown and this invention is demonstrated in detail, this invention is not limited to these Examples. In the following examples,% indicates mass%.
(Examples 1-5, Comparative Examples 1-4)
[Preparation of aqueous liquid composition]
A 100 mL aqueous liquid composition was prepared by a conventional method so as to have the composition and pH shown in Tables 1 and 2 below.
The obtained aqueous liquid composition was made into a paper pack 1 (trade name “TBA”, manufactured by Nippon Tetra Pak Co., Ltd., thickness: about 0.4 mm, length: about 30 mm, width: about 40 mm, height: about 85 mm. , And a liquid product for internal use was obtained.
The main configuration of the paper pack 1 is as follows.
<Main configuration> (Outside of container) Paper layer / Aluminum layer / Polyethylene layer (Inside of container: innermost layer)
The following evaluation was performed about the obtained liquid medicine for internal use.

[Evaluation of delamination]
Each liquid product for internal use was stored at 50 ° C. for 1 week, and after storage, the aluminum foil layer part of the container was visually observed, and delamination (delamination of aluminum layer) was evaluated based on the following evaluation criteria. . The results are also shown in Tables 1-2.
(Evaluation criteria: It was judged that the effect of the present invention could be confirmed by an evaluation of “No”.)
None: Generation of delamination in the aluminum foil layer was not confirmed.
Existence: Delamination was confirmed in the aluminum foil layer.

[Evaluation of vitamin stability]
Each liquid product for internal use is stored at 50 ° C. for 1 week, and after storage, the contents of thiamine nitrate, nicotinamide and ascorbic acid in the aqueous liquid composition are determined by high performance liquid chromatography, respectively. The stability of each was evaluated based on this. The results are also shown in Tables 1-2.
(Evaluation criteria: It was judged that the effect of the present invention could be confirmed with an evaluation of “◯” or more.)
<Stiamin nitrate stability>
A: Very stable (residual rate with respect to initial value is more than 85% and not more than 100%).
○: Stable (residual rate with respect to initial value is more than 75% and 85% or less).
X: Unstable (residual rate with respect to initial value is 75% or less).
<Nicotinamide stability>
A: Very stable (residual rate with respect to initial value is more than 90% and 100% or less).
○: Stable (residual rate with respect to initial value is more than 80% and 90% or less).
X: Unstable (residual rate with respect to initial value is 80% or less).
<Ascorbic acid stability>
A: Very stable (residual rate with respect to initial value is more than 80% and 100% or less).
○: Stable (residual rate with respect to initial value is more than 65% and not more than 80%).
X: Unstable (residual rate with respect to initial value is 65% or less).

As shown in the above results, in the liquid preparations for internal use of Examples 1 to 5, there was no occurrence of delamination of the aluminum layer, and the stability of vitamins was also good.
On the other hand, in Comparative Example 1 in which the pH of the aqueous liquid composition was 4.0 and Comparative Example 2 in which glucuronic acid was not added and the pH was 4.5, there was no delamination of the aluminum layer. The vitamin stability was poor. Further, in Comparative Examples 3 to 4 in which the pH was set to 3.5 using hydrochloric acid or acetic acid without adding glucuronic acid, delamination of the aluminum layer was observed.

(Examples 6 to 10, Comparative Examples 5 to 8)
The paper pack 1 used in Examples 1 to 5 and Comparative Examples 1 to 4 is the same as the paper pack 1 except that the material of the innermost layer is polypropylene (trade name “TBA”, Nippon Tetra Pak) Same as Examples 1 to 5 and Comparative Examples 1 to 4 except that the thickness is about 0.4 mm, the length is about 30 mm, the width is about 40 mm, and the height is about 85 mm. Thus, a liquid preparation for internal use was obtained and evaluated in the same manner as described above.
As a result, the same results as in Examples 1 to 5 and Comparative Examples 1 to 4 were obtained in Examples 6 to 10 and Comparative Examples 5 to 8, both in terms of delamination in the aluminum layer and vitamin stability.

(Examples 11 to 15)
A 100 mL aqueous liquid composition was prepared by a conventional method so as to have the composition and pH shown in Table 3 below.
The obtained aqueous liquid composition was accommodated in the same paper pack 1 as used in Examples 1 to 5 and Comparative Examples 1 to 4 to obtain liquid medicine products for internal use.
About the obtained liquid medicine for internal use, evaluation similar to Examples 1-5 and Comparative Examples 1-4 was performed. As a result, good results were obtained for both delamination generation and vitamin stability of the aluminum layer.

(Examples 16 to 20)
Except having changed the paper pack 1 to the paper pack 2, the liquid medicine product for internal use was obtained like Example 11-15, and evaluation similar to the above was performed.
As a result, good results were obtained in both the delamination generation and the vitamin stability of the aluminum layer as in Examples 11-15.

It is a schematic perspective view which shows an example of the paper container used in this invention.

Explanation of symbols

  11 ... Container

Claims (3)

Thiamine, thiamine nitrate, thiamine hydrochloride, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate ester, dicetiamine hydrochloride, fursultiamine hydrochloride, octothiamine, chicotiamine, bisbutiamine, bisbenchamine, fursultiamine, prosultiamine, Vitamins and / or derivatives thereof (A) that are at least one selected from the group consisting of benfotiamine, nicotinamide, ascorbic acid, ascorbate, ascorbic acid ester and L-ascorbic acid-2-glucoside ;
Or glucuronic acid, or glucuronic acid, lactic acid, butyric acid, malic acid, aspartic acid, glutamic acid, adipic acid, gluconic acid, tartaric acid, succinic acid, at least one member selected from the group consisting of maleic acid and fumaric acid contains an organic acid (B) is a combination of, and the aqueous liquid composition is pH3.5 or less, at least a paper layer, an aluminum layer and the resin layer is Do Ri innermost from said laminated sheet formed by laminating in this order A liquid preparation for internal use, which is filled in a paper container which is a resin layer .   The liquid preparation for internal use according to claim 1, wherein the compounding amount of the organic acid (B) in 100 mL of the aqueous liquid composition is 50 mg / min to 10000 mg / min. The liquid preparation for internal use according to claim 1 or 2 , further comprising an organic acid other than the organic acid (B) and / or an inorganic acid (C).

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