JP2008088116A - Aqueous liquid preparation composition for internal use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an aqueous liquid preparation composition prevented from dregs development under low-pH conditions of pH 3.5 or lower and excellent in appearance stability. <P>SOLUTION: The aqueous liquid preparation composition contains sparingly water-soluble galenical extract, a polyvinyl pyrrolidone and sugar alcohol(s) and is characterized by being 2.0-3.5 in pH value. In this composition, the sugar alcohol is preferably erythritol and/or xylitol, the polyvinyl pyrrolidone is preferably 30-95 in K-value, and the sparingly water-soluble galenical extract is preferably coix seed extract. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an aqueous oral solution composition containing a herbal extract.

Conventionally, in oral liquid preparations containing herbal medicines, there is a problem that so-called starch such as turbidity and precipitation derived from herbal medicines is likely to occur, and appearance stability is poor, and its prevention is a big problem from the viewpoint of commerciality and effectiveness of the preparation It has become.
Until now, various proposals have been made for the purpose of preventing the occurrence of starch in an internal solution containing a crude drug. Conventionally, polyvinylpyrrolidone is mainly used for this purpose (see, for example, Patent Documents 1 and 2). Patent Document 3 describes that polyvinyl pyrrolidone and polyoxyethylene hydrogenated castor oil are used in combination, and Patent Document 4 describes that polyvinyl pyrrolidone and a nonionic surfactant are used in combination. Yes.
Japanese Patent Laid-Open No. 10-45627 JP 2000-38345 A Japanese Patent Laid-Open No. 61-268627 JP 2003-246744 A

It is considered that it is desirable to set the pH of an oral solution containing a crude drug, particularly an aqueous oral solution containing a crude drug extract, from the viewpoint of flavor and antiseptic properties.
However, polyvinyl pyrrolidone cannot exert a satisfactory effect on the stabilization of an aqueous internal preparation containing a herbal extract under low pH conditions, particularly pH conditions of 3.5 or less.
Further, under low pH conditions, the nonionic surfactant is susceptible to hydrolysis, and there is a problem that precipitates derived from the surfactant are generated over time. Therefore, it is difficult to use a nonionic surfactant.
Therefore, until now, it has been difficult to prevent the occurrence of starch under low pH conditions of pH 3.5 or less in aqueous liquid preparations containing a crude drug extract. In particular, as a crude drug of a crude drug extract, a poorly water-soluble component ( In the case of blending a poorly water-soluble herbal extract using a crude drug containing a large amount of lipids and the like, the generation of starch was remarkable because it contained many poorly water-soluble components.
An object of the present invention is to provide an aqueous oral liquid composition that is prevented from generating starch under a low pH condition of pH 3.5 or less and is excellent in appearance stability.

As a result of intensive studies to solve the above-mentioned problems, the present inventors have combined polyvinylpyrrolidone and a sugar alcohol with respect to a poorly water-soluble crude drug extract within a pH range of 2.0 to 3.5. It discovered that generation | occurrence | production of the starch in the aqueous | water-based internal use liquid medicine composition containing a poorly water-soluble crude drug extract can be prevented effectively, and came to complete this invention.
That is, the present invention is an aqueous oral liquid composition comprising a poorly water-soluble crude drug extract, polyvinylpyrrolidone and sugar alcohol, and having a pH of 2.0 to 3.5.

  According to the present invention, it is possible to provide a water-based oral solution composition that is prevented from generating starch under a low pH condition of pH 3.5 or less and is excellent in appearance stability.

<Liquid water-soluble herbal extract>
In the present specification and claims, “poorly water-soluble crude drug extract” means fats, fatty oils, higher fatty acids having 12 or more carbon atoms and derivatives thereof, and proteins as crude drugs (raw drug substances) that are raw materials of the extracts Is an extract using a crude drug having a large amount of water-insoluble compounds (hereinafter referred to as “oil”) such as 3% by mass or more with respect to the dry mass of the drug substance and having low solubility in water It is.
Whether the crude drug extract to be used is a “poorly water-soluble crude drug extract” means that the light transmittance at a wavelength of 600 nm of an aqueous solution having a solid content concentration of 10% (hereinafter, “light transmittance of a 10% aqueous solution (600 nm)”) The lower the solubility of the herbal extract in water, the lower the light transmittance (600 nm) of the 10% aqueous solution.
In the present invention, the “poorly water-soluble crude drug extract” is preferably a crude drug extract having a light transmittance (600 nm) of 10% aqueous solution of 30% or less, more preferably 20% or less. An aqueous internal liquid composition containing a crude drug extract having a light transmittance (600 nm) of 30% or less in a 10% aqueous solution is usually prone to starch and poor in appearance stability, but the aqueous internal liquid composition of the present invention. Shows excellent appearance stability even when a crude drug extract having a light transmittance (600 nm) of a 10% aqueous solution of 30% or less is blended.
The lower limit of the light transmittance (600 nm) of the 10% aqueous solution is preferably 1.0% or more and more preferably 5.0% or more in view of the appearance stability of the aqueous oral liquid composition.
Specifically, the light transmittance (600 nm) of a 10% aqueous solution can be determined by the following procedure.
[Method of measuring light transmittance (600 nm) of 10% aqueous solution]
Add 9 mL of water to 1 g of herbal extract solids and shake at room temperature (25 ° C.) for 30 minutes. The light absorbance (600 nm) of the obtained liquid is measured with a spectrophotometer using the water absorbance as a blank (reference).

As the poorly water-soluble crude drug extract, a commercially available extract may be used, or an extract prepared by solvent extraction from the drug substance may be used.
As long as the extraction solvent of the extract can be taken orally, the extract can be used as it is as a sparingly water-soluble crude drug extract. Further, the extract may be used as a diluted solution diluted with an appropriate solvent. Alternatively, the extract may be a concentrated extract, a dry powder, or a paste obtained by evaporating the extraction solvent or freeze-drying.
Examples of the extraction solvent include water and / or an organic solvent such as ethanol.
In the present invention, the extraction solvent is most preferably water. That is, in the present invention, it is most preferable to use a water extract as the poorly water-soluble crude drug extract. When the extraction solvent is water, the extract can be blended as it is as a sparingly water-soluble herbal extract, and the resulting aqueous oral liquid composition has good flavor.
As a method for water extraction, a conventionally known method can be used, and in particular, a method in which extraction is performed with hot water and coarse filtration is preferably used.

Specific examples of the crude drug of the poorly water-soluble crude drug extract include crude drugs belonging to seeds or fruits.
Among the crude drugs belonging to seeds, those containing 3% by mass or more of oil include yokuinin, kyounin, ketsumeishi, sansonin, tonin, nikuzu and the like.
Among the active ingredients belonging to fruits, those containing 3% by mass or more of oil include fennel, ages, pheasants, pepper, trash, and shrimp.
Among these, at least one selected from the group consisting of Yokuinin, Kyonin and Fennel is preferable, and Yokuinin is particularly preferable.
Yokuinin is a traditional Chinese medicine name for pearl barley and normally threshed seeds are used. In the present invention, decoction without threshing can also be used.
Yokuinin extract is an ingredient that is expected to have a beautiful skin effect, and has long been used as a folk remedy against warts and rough skin. The water extract extracted from Yokuinin according to a conventional method contains many poorly water-soluble components, and the light transmittance (600 nm) of the 10% aqueous solution is often 20% or less.

There is no restriction | limiting in particular as a compounding quantity of a poorly water-soluble crude drug extract in the aqueous | water-based internal use liquid composition of this invention, According to the objective, it can select suitably. The blending amount is particularly preferably 100 to 10,000 mg / 100 mL, more preferably 200 to 5,000 mg / 100 mL in terms of bulk drug substance. When the amount is 100 mg / 100 mL or more, the amount of oil in the aqueous oral liquid composition is large, and the effects of the present invention are sufficiently exhibited. When the amount is less than 100 mg / 100 mL, the amount of oil is not large, so that even when polyvinyl pyrrolidone and / or sugar alcohol is not contained, a certain degree of appearance stability is ensured. Further, when the blending amount is 10,000 mg / 100 mL or less, turbidity and precipitation hardly occur, and the appearance stability is excellent. In particular, when it is 5,000 mg or less, the production suitability is excellent.
Here, the “concentration of crude drug” is a value obtained by converting the amount of the poorly water-soluble crude drug extract blended in the aqueous oral liquid composition into the amount of the drug substance used for the preparation of the poorly water-soluble crude drug extract. is there.

<Polyvinylpyrrolidone>
Polyvinylpyrrolidone is a linear polymer of 1-vinyl-2pyrrolidone and is also called povidone. The stabilization effect of the aqueous oral liquid composition with polyvinylpyrrolidone is presumed to be that the oil in the poorly water-soluble crude drug extract is stabilized while maintaining a finely dispersed state due to electrical repulsion and viscosity due to polyvinylpyrrolidone.
Polyvinyl pyrrolidone having a K value of 15 to 100 is generally known.
The K value is a value indicating the viscosity characteristic obtained by the measurement method described in the “Povidone” section of each article of the Pharmaceuticals, Part 14 of the “14th revised Japanese Pharmacopoeia”.
Commercially available polyvinylpyrrolidone has symbols such as K15, K29 / 32, K30, K60, K90, etc., depending on the K value. For example, polyvinylpyrrolidone K-90 (manufactured by BASF, K value 90), Polyvinylpyrrolidone K-30 (manufactured by BASF, K value 30), polyvinylpyrrolidone K-25 (manufactured by BASF, K value 25) and the like.
In addition, when the K value of commercially available polyvinyl pyrrolidone is measured by the above measuring method, the measured K value is usually 90 to 108% of the K value displayed on the commercially available product.

  The polyvinyl pyrrolidone used in the present invention is excellent in the stabilizing effect of the aqueous oral liquid composition, and therefore, the K value is preferably 30 to 95, more preferably 60 to 95, and 80 to 95. More preferably.

  In the aqueous oral liquid composition of the present invention, the amount of polyvinylpyrrolidone is preferably 1 mg / 100 mL to 5.0 g / 100 mL, more preferably 10 mg / 100 mL to 3.0 g / 100 mL, and 50 mg / 100 mL to 1.0 g. / 100 mL is more preferable. If it is 1 mg / 100 mL or more, the stabilizing effect is high, and if it is 5.0 g / 100 mL or less, the texture as an internal solution is excellent.

<Sugar alcohol>
In the present invention, the sugar alcohol, together with the polyvinyl pyrrolidone, suppresses the generation of starch under the conditions of pH 2.0 to 3.5, and contributes to the improvement of the appearance stability of the aqueous oral liquid composition.
Any sugar alcohol may be used as long as it can be taken internally, and for example, one or more selected from sorbitol, erythritol, xylitol, mannitol, maltitol, inositol and the like can be used. Among these, erythritol and / or xylitol are preferable because of the excellent effects of the present invention.

  In the aqueous oral solution composition of the present invention, the amount of sugar alcohol is preferably 0.01 to 10 parts by mass, and 0.1 to 5 parts by mass with respect to 1 part by mass of the raw drug equivalent of the poorly water-soluble crude drug extract. More preferably, 0.5-3 mass parts is further more preferable. If the amount is 0.01 parts by mass or more, the stabilizing effect is high, and the flavor of the resulting aqueous oral liquid composition is also improved. A flavor is favorable in it being 10 mass parts or less.

The aqueous oral solution composition of the present invention preferably further contains one or more selected from the group consisting of glucuronolactone, vitamins and derivatives thereof.
The aqueous oral solution composition of the present invention also has the stabilizing effect of glucuronolactone, vitamins and derivatives thereof by containing the polyvinyl pyrrolidone and the sugar alcohol. Therefore, in the aqueous oral liquid composition of the present invention, Glucuronolactone, vitamins and derivatives thereof can exist stably.

Glucuronolactone is a white to slightly yellowish white crystal or crystalline powder. Glucuronolactone is a component that has been used for the treatment of liver function improvement, urticaria, eczema, poisoning rash, pregnancy embarrassment, pregnancy toxemia, etc. It is a useful drug that is known to be effective as a preventive agent for alcoholic fatty liver. The glucuronolactone in the present invention is used in the meaning including glucuronolactone itself and glucuronic acid or a salt thereof.
Glucuronolactone may be a commercially available product or may be appropriately synthesized. The method for synthesizing the glucuronolactone is not particularly limited and may be appropriately selected depending on the intended purpose.
There is no restriction | limiting in particular as a compounding quantity of a glucuronolactone in the aqueous | water-based internal use liquid composition of this invention, According to the objective, it can select suitably. For example, for the purpose of improving liver function, the mg / mL unit is preferably, for example, 10 mg / 100 mL to 2,000 mg / 20 mL, and 100 mg / 100 mL to 1,000 mg / 20 mL with respect to the total volume of the aqueous oral solution composition. More preferred.
When the amount is not less than the lower limit of the above range, the above object can be sufficiently achieved, and when the amount is not more than the upper limit, the flavor of the aqueous oral liquid composition is good. Since glucuronolactone has a peculiar unpleasant taste (bitter taste), the smaller the blending amount, the better the flavor of the aqueous oral liquid composition.

There is no restriction | limiting in particular as a kind and compounding quantity of a vitamin or its derivative (these are collectively called vitamins hereafter), According to the objective, it can select suitably. As vitamins, water-soluble vitamins such as vitamin B and vitamin C and / or derivatives thereof are particularly preferable.
Examples of vitamin B or derivatives thereof include vitamin B1 such as thiamine and thiamine nitrate or derivatives thereof; vitamin B2 such as riboflavin and phosphate riboflavin or derivatives thereof; vitamin B6 such as pyridoxine and pyridoxine hydrochloride or derivatives thereof; cyanocobalamin and the like Vitamin B12 or a derivative thereof; nicotinamide; calcium pantothenate and the like.
Examples of vitamin C or derivatives thereof include ascorbic acid, L-ascorbic acid stearate, sodium L-ascorbate and the like.
Moreover, vitamin E, such as tocopherol and tocopherol acetate, or a derivative thereof can also be used.
Said vitamins can be used individually by 1 type or in combination of 2 or more types.

  In addition to the above-mentioned components, the aqueous oral solution composition of the present invention is a sweetener, preservative, stabilizer, pH adjuster, preservative, antioxidant, as long as the effects of the present invention are not impaired. , Flavoring agents / fragrances, cooling agents, coloring agents, buffering agents, herbal medicines, caffeine, royal jelly, and other optional components. 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.

  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 sugar Fructose liquid sugar, glucose, powdered reduced maltose water candy, water candy, high glucose water candy, lactose, sucrose, purified white sugar, purified white sugar spherical granules, honey, purified honey, simple syrup, aspartame, acesulfame potassium, amacha extract, licorice Licorice extract, saccharin, sodium saccharin, sucralose, stevia extract, neotame, thaumatin, glycine, glycerin, dipotassium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, monoammonium glycyrrhizinate and the like. Said sweetener 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, ethanol, disodium calcium edetate, sodium edetate, erythorbic acid, sodium ersorbate, calcium chloride, chloride Sodium, magnesium chloride, cysteine hydrochloride, cacao butter, fructose, carboxyvinyl polymer, carmellose calcium, carmellose sodium, hydrous silicon dioxide, dry sodium sulfite, dry aluminum hydroxide Gel, dry aluminum hydroxide gel, dry sodium carbonate, xanthan gum, citric acid, calcium citrate, sodium citrate, glycine, glycerin, glyceryl fatty acid ester, disodium glycyrrhizinate, glucono-δ-lactone, calcium gluconate, light anhydrous Silicic acid, crystalline cellulose, acetic acid, sodium acetate, sodium salicylate, phenyl salicylate, β-cyclodextrin, dibutylhydroxytoluene, tartaric acid, sucrose fatty acid ester, calcium hydroxide, sodium hydroxide, magnesium hydroxide, purified gelatin, purified soybean Lecithin, refined sucrose, sorbitan sesquioleate, cetanol, gelatin, sorbitan fatty acid ester, soybean oil unsaponifiable matter, dextran, lactic acid, lactose, concentrated glycerin, sucrose, Palau Ethyl benzoate, butyl paraoxybenzoate, methyl paraoxybenzoate, microcrystalline cellulose, hydroxypropylcellulose, glacial acetic acid, sodium pyrosulfite, butylhydroxyanisole, glucose, fumaric acid, monosodium fumarate, propylene glycol, bentonite, boro Acid, propyl gallate, partially neutralized polyacrylic acid, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, polysorbate, polyvinyl alcohol, polyvinyl alcohol / dibutyl ether mixture, macrogol, maltose, maleic acid, malon Acid, anhydrous citric acid, anhydrous sodium citrate, anhydrous sodium pyrophosphate, maleic anhydride, sodium metaphosphate, methylcellulose, l-menthol, monostearate Aluminum phosphate, glyceryl monostearate, medicinal carbon, sodium lauryl sulfate, ovalbumin, etc. DL- malic acid. Said stabilizer can be used individually by 1 type or in combination of 2 or more types.

  The pH adjuster is not particularly limited and may be appropriately selected depending on the intended purpose. For example, hydrochloric acid, dilute hydrochloric acid, citric acid, sodium citrate, glycine, succinic acid, acetic acid, tartaric acid, D-tartaric acid, water Sodium oxide, potassium hydroxide, magnesium hydroxide, lactic acid, calcium lactate, glacial acetic acid, monosodium fumarate, propionic acid, maleic acid, anhydrous citric acid, DL-malic acid, aspartic acid, glutamic acid, adipic acid, gluconic acid, Examples include fumaric acid, valeric acid, butyric acid, isobutyric acid, methylbutyric acid, sodium hydrogen carbonate, and the like. Among these, dilute hydrochloric acid, acetic acid, and butyric acid are preferable because the flavor of the aqueous oral solution composition is good. Said pH adjuster can be used individually by 1 type or in combination of 2 or more types.

The preservative is not particularly limited and may be appropriately selected depending on the intended purpose. For example, aminoethylsulfonic acid, benzoic acid, sodium benzoate, ethanol, sodium edetate, agar, dl-camphor, citric acid , Sodium citrate, salicylic acid, sodium salicylate, phenyl salicylate, dibutylhydroxytoluene, sorbic acid, potassium sorbate, dehydroacetic acid, sodium dehydroacetate, 2-naphthol, sucrose, honey, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, paraoxy Examples thereof include ethyl benzoate, butyl paraoxybenzoate, propyl paraoxybenzoate, methyl paraoxybenzoate, 1-menthol, and eucalyptus oil. Said antiseptic | preservative can be used individually by 1 type or in combination of 2 or more types.
As the fragrance, fragrances such as acerola, pineapple, apple, peach, strawberry, blueberry, grape, grapefruit, lemon, orange and ume are preferable.

Among the above, the aqueous oral liquid composition of the present invention preferably contains an organic acid. Thereby, the flavor of an aqueous | water-based internal use liquid preparation composition improves.
As the organic acid, carboxylic acids such as acetic acid, lactic acid, butyric acid, and tartaric acid are preferable, and butyric acid is particularly preferable.
In the aqueous oral liquid composition of the present invention, the blending amount of the organic acid is preferably 0.1 to 500 mg / 100 mL, and more preferably 0.5 to 50 mg / 100 mL. Within the above range, the effect of improving the flavor is excellent.

The nonionic surfactant is easily hydrolyzed under low pH conditions, and the hydrolyzate causes generation of starch in the aqueous oral solution composition.
Therefore, it is preferable that content of a nonionic surfactant is 0.02 mass% or less of the total volume of an aqueous | water-based internal liquid composition in the aqueous | water-based internal liquid composition of this invention. When the amount is 0.02% by mass or less, starch is hardly generated, and the appearance stability of the aqueous oral liquid composition is high. The flavor is also good.
In the aqueous oral liquid composition of the present invention, the less nonionic surfactant is preferred, and 0%, that is, most preferably not contained.

The aqueous oral solution composition of the present invention contains water as a solvent.
The aqueous oral solution composition of the present invention may further contain, as a solvent, a lower alcohol having 1 to 3 carbon atoms such as ethanol, as long as the effects of the present invention are not impaired.
However, if the lower alcohol is contained, the flavor of the aqueous oral solution composition may be impaired. Therefore, the blending amount of the lower alcohol in the aqueous oral solution composition is preferably less than 0.5% by mass of the total volume, 0 Less than 0.1% by mass is more preferable, and less than 0.06% by mass is more preferable. Considering the flavor, 0% is most preferable.

The aqueous oral liquid composition of the present invention has a pH in the range of 2.0 to 3.5. By being in this range, generation | occurrence | production of the starch derived from a poorly water-soluble crude drug extract is suppressed, and also it is excellent in flavor, antisepticity, etc. Moreover, when vitamins and glucuronolactone are contained, the stability of these components is also high.
The pH of the aqueous oral liquid composition of the present invention is preferably 2.0 to 3.0, more preferably 2.0 to 2.8.
The aqueous oral liquid composition of the present invention has a pH at 20 ° C.

EXAMPLES Next, although an Example is shown and this invention is demonstrated in detail, this invention is not limited to these Examples.
<Examples 1-8, Comparative Examples 1-3>
[Preparation of aqueous oral liquid composition]
Each component was mixed by a conventional method so as to have the composition and pH shown in Tables 1 and 2 to prepare a 100 mL aqueous oral liquid composition. The numerical value shown in the table is the blending amount (mg) in 100 mL of the aqueous oral liquid composition.
(* 1) to (* 6) in Tables 1 and 2 are as follows.
(* 1): Water extract of Yokuinin (manufactured by Nippon Powder Chemical Co., Ltd., light transmittance of 10% aqueous solution (600 nm): 10%).
(* 2): Yokuinin ethanol extract (manufactured by Nippon Powder Chemical Co., Ltd., ethanol content: 30%, light transmittance of 10% aqueous solution (600 nm): 90%).
(* 3): Polyvinylpyrrolidone K-90 (Kollidon 90F, manufactured by BASF Corporation. K value: 90).
(* 4): Polyvinylpyrrolidone K-30 (Kollidon 30, manufactured by BASF Corp., K value: 30).
(* 5): Polyvinylpyrrolidone K-25 (Kollidon 25, manufactured by BASF Corporation. K value: 25).
(* 6): Polyoxyethylene sorbitan fatty acid ester having an average addition mole number of ethylene oxide of 20 mol (trade name: polysorbate 80, manufactured by Nikko Chemicals Co., Ltd.).

[Appearance stability evaluation]
About the obtained aqueous | water-based internal use liquid preparation composition, the external appearance stability was evaluated in the following procedures.
Each aqueous internal liquid composition was prepared and stored for 1 week at 25 ° C., and each aqueous internal liquid composition after storage was observed and evaluated according to the following evaluation criteria. The results are also shown in Tables 1-2.
(Evaluation criteria)
○: No starch (precipitate) was generated in the composition, and no suspended matter was observed.
(Triangle | delta): Although the suspended | floating matter was seen in the composition, starch did not generate | occur | produce.
X: Starch was generated in the composition.

As shown in the above results, the aqueous oral liquid compositions of Examples 1 to 7 containing all of yokuinin extract, polyvinyl pyrrolidone and sugar alcohol did not generate starch in any of the examples and had good appearance stability. It was.
Among these, when Examples 3 to 5 having the same composition and pH except for the kind of polyvinylpyrrolidone used were compared, no starch was generated in Example 5 using polyvinylpyrrolidone having a K value in the range of 25. However, some floating matter was seen.
On the other hand, the aqueous internal use liquid composition of the comparative example 1 which did not mix | blend polyvinyl pyrrolidone, the comparative example 2 which did not mix | blend sugar alcohol, and the comparative example 3 which mix | blended nonionic surfactant instead of polyvinyl pyrrolidone is starch. The appearance stability was poor.

[Taste evaluation]
About the aqueous internal use liquid composition of Examples 1, 3-8 prepared above and Comparative Examples 2-3, sensory evaluation about the taste at the time of drinking was performed by 10 panelists immediately after preparation. From the results, the flavor was evaluated according to the following evaluation criteria.
(Evaluation criteria)
(Double-circle): 9-10 people evaluated that 10 people were preferable.
○: 7 to 8 out of 10 people were evaluated as preferable.
(Triangle | delta): 4-6 people evaluated that 10 people were preferable.
X: It was evaluated that 0 to 3 out of 10 people are preferable.

Further, as Reference Example 1, an aqueous internal liquid composition having the same composition as Example 1 was prepared except that the pH was 4.0, and the flavor evaluation was performed in the same manner as described above.
These results are shown in Table 3 together with the pH of each composition.

As shown to the said result, all the aqueous | water-based internal use liquid composition of Example 1,3-5,7-8 were good in flavor, and especially the flavor of Example 8 which mix | blended butyric acid was excellent. However, the aqueous oral liquid composition of Example 6 was bad in flavor. This is presumed to be due to the influence of ethanol.
The aqueous oral solution composition of Comparative Examples 2 to 3 and the aqueous oral solution composition of Reference Example 1 having a pH of 4.0 did not have a good taste.

[Glucuronolactone stability evaluation]
The aqueous internal liquid compositions of Examples 7 to 8 prepared above were stored for 2 months at 50 ° C. after preparation, and the amount of glucuronolactone in each aqueous internal liquid composition after storage was measured by liquid chromatography. Measured graphically. From the result, the residual ratio (%) was obtained by the following formula.
(Calculation formula) Residual rate (%) = (glucuronolactone amount after storage / glucuronolactone amount before storage) × 100

Further, as Reference Example 2, an aqueous internal liquid composition having the same composition as Example 7 was prepared except that the pH was 4.0, and glucuronolactone stability was evaluated in the same manner as described above.
These results are shown in Table 4 together with the pH of each composition.

As shown in the above results, in the aqueous oral liquid compositions of Examples 7 to 8, 90% or more of glucuronolactone remains even after storage at 50 ° C. for 2 months, and the stability of glucuronolactone is high. it was high.
On the other hand, the residual rate of the aqueous oral liquid composition of Reference Example 2 having a relatively high pH of 4.0 was 80%.

<Examples 9 to 16>
Each component was mixed by a conventional method so as to have the composition and pH shown in Table 5 to prepare a 100 mL aqueous oral liquid composition. The numerical value shown in the table is the blending amount (mg) in 100 mL of the aqueous oral liquid composition.
(* 1) and (* 3) in Table 5 are the same as (* 1) and (* 3) in Tables 1 and 2, respectively.
About the obtained aqueous | water-based internal use liquid preparation composition, the external appearance stability and flavor were evaluated similarly to the above. The results are also shown in Table 5.

As shown in the above results, although some floating matter was observed in Example 13, no occurrence of starch (precipitation) was observed in any of Examples 9-16.
Moreover, about the flavor, although the aqueous | water-based internal use liquid composition of Examples 10-16 was all favorable, the aqueous | water-based internal use liquid composition of Example 9 was a little inferior. This is presumed to be affected by the blending amount of polyvinylpyrrolidone.

  As is clear from the above results, the aqueous oral liquid composition of the present invention containing polyvinylpyrrolidone and sugar alcohol together with a poorly water-soluble crude drug extract has no appearance of starch and is excellent in appearance stability. Moreover, flavor is also improved by not containing alcohol and nonionic surfactant. Furthermore, in the aqueous oral solution composition of the present invention, the stability of glucuronolactone is also good.

Claims (7)

  An aqueous oral liquid composition comprising a poorly water-soluble herbal extract, polyvinylpyrrolidone and sugar alcohol, and having a pH of 2.0 to 3.5.   The aqueous oral liquid composition according to claim 1, wherein the sugar alcohol is erythritol and / or xylitol.   The aqueous oral liquid composition according to claim 1 or 2, wherein the polyvinylpyrrolidone has a K value of 30 to 95.   The aqueous oral liquid composition according to any one of claims 1 to 3, wherein the poorly water-soluble crude drug extract is a Yokuinin extract.   Furthermore, the aqueous | water-based internal liquid composition as described in any one of Claims 1-4 containing 1 or more types selected from the group which consists of glucuronolactone, a vitamin, and its derivative (s).   Furthermore, the aqueous | water-based internal solution composition as described in any one of Claims 1-5 containing an organic acid.   Content of nonionic surfactant is 0.02 mass% or less of a total volume, The aqueous | water-based internal use liquid composition as described in any one of Claims 1-6.