JP5398100B2 - Oral liquid composition containing iron compound - Google Patents

Description

The present invention relates to an internal solution composition in which a water-soluble polymer is blended with an internal solution containing iron ions. More specifically, by adding one or more selected from polyethylene glycol, polyvinyl alcohol, and polyvinylpyrrolidone to an internal solution containing divalent iron ions, the unpleasant taste (convergence) of iron ions can be suppressed. The present invention also relates to an internal use liquid composition with improved dosing properties.

Iron is a component required for hemoglobin of red blood cells, and if it is insufficient, it tends to get tired or present symptoms such as anemia. Changes in dietary habits have led to a decrease in iron intake. Therefore, in recent years, many pharmaceuticals and foods containing iron have been marketed.

  However, liquids for internal use containing an iron compound are difficult to drink due to an unpleasant taste derived from iron ions. This taste is the same as the taste when using an astringent that binds to proteins such as tannin and alum (astringent taste).

  So far, various techniques for improving the unpleasant taste of drugs and foods containing iron compounds have been disclosed (Patent Document 1, Patent Document 2, Patent Document 3).

JP 2002-80375 A JP 2003-73284 A International Publication No. 03/000246 Pamphlet

An object of the present invention is to provide an internal solution composition that reduces the astringent taste derived from iron ions, is easy to drink, and does not leave an unpleasant aftertaste.

  In order to solve the above-mentioned problems, the present inventors have conducted intensive studies. As a result, when at least one selected from polyethylene glycol, polyvinyl alcohol, and polyvinylpyrrolidone is added to iron ions, protein aggregation (convergence) by iron ions is achieved. And the astringency is improved, and the present invention has been completed.

  That is, the present invention is an internal liquid composition containing one or more selected from polyethylene glycol, polyvinyl alcohol and polyvinylpyrrolidone in an internal liquid containing iron ions.

  The iron ion in the present invention refers to a divalent iron ion, which is generated when a divalent iron compound is dissolved in an aqueous solution or a trivalent iron compound dissolved in an aqueous solution. It is an iron ion generated when trivalent iron ions are reduced. As the iron compound to be blended, a divalent iron compound is used, and examples thereof include ferrous fumarate, ferrous sulfate, and sodium ferrous citrate. These may be blended singly or in combination of two or more. Further, when a trivalent iron compound is added, the trivalent iron ion may be reduced to a divalent iron ion by a reducing substance (for example, a reducing organic acid such as reducing sugar or ascorbic acid). Divalent iron ions have the property of improving the absorbability from the digestive tract.

The blending amount of the divalent iron ion in the present invention can be appropriately selected and used according to the purpose.
In terms of nutrient intake, converted to iron ions in iron compounds, 0.5 per day
-60 mg is preferable, for example, 0.0005 to 0.06 W / V% when converted to 100 mL. In particular, when the iron ion blending amount is 0.002 w / v% or more, the astringency is increased and the ingestibility is very poor. Therefore, in the oral solution composition of the present invention, the effect is more obtained when the iron ion concentration is 0.002 w / v% or more.

  The polyethylene glycol in the present invention is a polyether having a structure that is considered to be generated by dehydration polycondensation of ethylene glycol, synthesized by anionic polymerization of ethylene oxide and cationic polymerization by proton initiation, and both ends are hydroxyl groups. . The polyethylene glycol used in the present invention usually has an average molecular weight of 150 to 35000, preferably 300 to 8000, and more preferably 300 to 3000.

  The blending ratio of the polyethylene glycol and the iron compound is 0.1 to 20000 parts by mass, preferably 1 to 2000 parts by mass, and more preferably 5 to 1000 parts by mass with respect to 1 part by mass of the iron ion. . As the polyethylene glycol of the present invention, commercially available products can be used.

  The polyvinyl alcohol in the present invention is polyvinyl alcohol and / or a copolymer composed of polyvinyl alcohol and polyvinyl acetate. Polyvinyl acetate obtained from a vinyl acetate monomer synthesized from acetic acid, oxygen and ethylene as a raw material is acidified. Or obtained by hydrolysis with alkali. The polymerization degree of the polyvinyl alcohol used in the present invention is usually 200 to 4000, preferably 500 to 3000, and more preferably 1000 to 2500. The saponification degree of the polyvinyl alcohol used in the present invention is usually 70% or more, preferably 80% or more, and more preferably 85% or more.

  The compounding ratio of such polyvinyl alcohol and the iron compound is 1 to 20000 parts by mass, preferably 5 to 4000 parts by mass, and more preferably 10 to 1000 parts by mass with respect to 1 part by mass of the iron ions. The polyvinyl alcohol of this invention can use what is marketed normally.

  The polyvinylpyrrolidone in the present invention is a polymer of N-vinyl-2-pyrrolidone, which can be obtained by adding a small amount of ammonia to a vinylpyrrolidone aqueous solution and polymerizing with a hydrogen peroxide catalyst. In addition to the hydrogen peroxide catalyst, sodium sulfite, peroxide, azo catalyst, and the like can be used to form the polymer. The K value of the polyvinylpyrrolidone used for this invention is 15-100 normally, Preferably it is 15-80, More preferably, it is 15-50. The K value here refers to the intrinsic viscosity and is the K value of the fixture.

  Such a blending ratio of polyvinylpyrrolidone and iron compound is 1 to 20000 parts by mass, preferably 5 to 4000 parts by mass, and more preferably 10 to 2000 parts by mass with respect to 1 part by mass of the iron ions. As the polyvinylpyrrolidone of the present invention, commercially available products can be used.

  The pH of the liquid composition of the present invention is 2.5 to 7.0, preferably 3.0 to 5.5. A liquid having a pH of less than 2.5 is difficult to drink due to its strong acidity, and if it exceeds pH 7.0, iron hydroxide precipitates, which is not preferable. The pH of the liquid is, for example, an organic acid such as citric acid, malic acid, fumaric acid, tartaric acid, lactic acid or succinic acid, a salt of these organic acids, an inorganic acid such as phosphoric acid or hydrochloric acid, or an inorganic base such as sodium hydroxide. Can be adjusted.

  Vitamins, minerals, other amino acids, herbal medicines, herbal extracts, caffeine, royal jelly, and the like can be appropriately added to the internal liquid composition of the present invention as long as the effects of the present invention are not impaired. Moreover, additives such as antioxidants, colorants, flavors, flavoring agents, surfactants, solubilizers, preservatives, sweeteners, and the like can be appropriately blended as necessary so long as the effects of the present invention are not impaired.

  The method for preparing the internal liquid composition of the present invention is not particularly limited. Usually, after dissolving each component with an appropriate amount of purified water, the pH is adjusted, the remaining purified water is added to adjust the volume, and if necessary, filtration and sterilization are performed to obtain the desired internal liquid composition. .

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide an oral liquid composition containing iron ions that reduces the astringent taste derived from iron ions, is easy to drink, and does not leave an unpleasant aftertaste. This oral solution composition can be applied to, for example, various preparations including pharmaceuticals and quasi-drugs such as syrups and drinks, and various beverages such as health drinks.

Hereinafter, the present invention will be described in more detail with reference to examples and test examples. An example is an example which shows an embodiment of the invention concretely, and a test example is an example of a test which evaluated an example.

Example 1
Ferrous fumarate 0.15g
Polyethylene glycol 5.00g
(Average molecular weight: 400)
Citric acid 0.10g
Sodium hydroxide Appropriate amount After the above components were dissolved in purified water, the pH was adjusted to 4.8, and purified water was added to make the total amount 100 mL, which was filled into a glass bottle and capped.
Similarly, in Examples 2 to 3 and Comparative Example, an internal solution containing each component was obtained.

(Example 2)
Ferrous fumarate 0.15g
Polyvinyl alcohol 5.00g
(Degree of saponification: 88% Degree of polymerization: 2400)
Citric acid 0.10g
Sodium hydroxide appropriate amount (Example 3)
Ferrous fumarate 0.15g
Polyvinylpyrrolidone 5.00g
(K value: 25)
Citric acid 0.10g
Sodium hydroxide appropriate amount (comparative example)
Ferrous fumarate 0.15g
Citric acid 0.10g
Sodium hydroxide appropriate amount (Example 4)
Ferrous fumarate 0.06g
Polyethylene glycol 1.00g
(Average molecular weight: 400)
0.01 g of thiamine nitrate
Riboflavin sodium phosphate 0.01 g
0.01 g of pyridoxine hydrochloride
Ascorbic acid 1.00g
Aminoethylsulfonic acid 2.00g
Xylitol 4.00g
Trehalose 5.00g
Erythritol 5.00g
Citric acid 0.80 g
Sodium citrate appropriate amount Sodium benzoate 0.06g
0.10g mixed fruit flavor
After dissolving the above components in purified water, the pH was adjusted to 3.0, and purified water was added to make up a total volume of 100 mL. This solution was filtered with a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled into a glass bottle and capped to obtain an internal solution.

(Example 5)
Ferrous fumarate 0.06g
Polyvinyl alcohol 0.50g
(Degree of saponification: 88% Degree of polymerization: 2400)
Calcium gluconate 2.00g
Magnesium aspartate 1.00 g
0.01 g of thiamine nitrate
Riboflavin 0.01g
0.10 g of pyridoxine hydrochloride
Ascorbic acid 1.00g
Aminoethylsulfonic acid 1.00g
Sorbitol 4.00g
Trehalose 5.00g
Xylitol 4.00g
Stevia extract 0.03g
Acesulfame potassium 0.03g
Malic acid 0.10g
Citric acid 0.40g
Sodium citrate appropriate amount Benzoic acid 0.06g
Butyl paraoxybenzoate 0.006g
Propyl paraoxybenzoate 0.006 g
Apple flavor 0.10g
After dissolving the above components in purified water, the pH was adjusted to 4.0, and purified water was added to make up a total volume of 100 mL. This solution was filtered with a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled into a glass bottle and capped to obtain an internal solution.

(Example 6)
Ferrous fumarate 0.06g
Polyvinylpyrrolidone 0.50g
(K value: 25)
Riboflavin sodium phosphate 0.01 g
0.01 g of pyridoxine hydrochloride
Ascorbic acid 1.00g
Cyanocobalamin 120μg
Panthenol 0.01g
Anhydrous caffeine 0.05g
Nicotinamide 0.05g
Aminoethylsulfonic acid 1.00g
Sucrose 2.00g
Sorbitol 2.50g
Trehalose 3.00 g
Indigestible dextrin 2.00g
Stevia extract 0.015g
Acesulfame potassium 0.015 g
Citric acid 0.40g
Malic acid 0.50g
Sodium malate appropriate amount potassium bicarbonate 0.50g
Benzoic acid 0.06g
Butyl paraoxybenzoate 0.006 g
Propyl paraoxybenzoate 0.006 g
0.10g mixed fruit flavor
After dissolving the above components in purified water, the pH was adjusted to 4.5, and purified water was added to make up a total volume of 100 mL. This solution was filtered with a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled into a glass bottle and capped to obtain an internal solution.

(Example 7)
Ferrous fumarate 0.06g
Polyglycerol fatty acid ester 0.20 g
Polyoxyethylene hydrogenated castor oil 0.10g
Polyvinylpyrrolidone 0.20g
(K value: 90)
Calcium gluconate 0.80 g
Magnesium aspartate 0.40 g
Tocopherol acetate 0.03g
0.01 g of thiamine nitrate
Riboflavin sodium phosphate 0.01 g
0.01 g of pyridoxine hydrochloride
Tricaprylin 0.05g
Nicotinamide 0.10g
Anhydrous caffeine 0.10g
Aminoethylsulfonic acid 2.00g
Yokuinin style extract 2.00mL
Glucose 5.00g
Indigestible dextrin 4.00 g
Erythritol 5.00g
Xylitol 2.00g
Stevia extract 0.02g
Acesulfame potassium 0.03g
Citric acid 0.80 g
Sodium citrate appropriate amount Sodium benzoate 0.06g
Butyl paraoxybenzoate 0.006g
Propyl paraoxybenzoate 0.006 g
Glycerin 0.20g
0.10g mixed fruit flavor
After dissolving the above components in purified water, the pH was adjusted to 3.5, and purified water was added to make up a total volume of 100 mL. This solution was filtered with a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled into a glass bottle and capped to obtain an internal solution.

(Example 8)
Ferrous fumarate 0.06g
Polyvinyl alcohol 0.30g
(Degree of saponification: 85% Degree of polymerization: 2000)
Calcium gluconate 2.00g
Calcium lactate 1.00g
Sodium aspartate 0.10g
Magnesium aspartate 1.00 g
0.01 g of thiamine nitrate
Riboflavin sodium phosphate 0.02g
0.03 g of pyridoxine hydrochloride
Nicotinamide 0.05g
Anhydrous caffeine 0.10g
Aminoethylsulfonic acid 2.00g
Yokuinin style extract 2.00mL
Royal jelly 0.60g
Glucose 5.00g
Sorbitol 5.00g
Xylitol 5.00g
Stevia extract 0.02g
Acesulfame potassium 0.03g
Citric acid 0.80 g
Sodium citrate 0.10g
Phosphoric acid 0.30 g
Hydrochloric acid appropriate amount Sodium benzoate 0.06g
Butyl paraoxybenzoate 0.006 g
Propyl paraoxybenzoate 0.006 g
0.10g mixed fruit flavor
After dissolving the above components in purified water, the pH was adjusted to 3.5, and purified water was added to make up a total volume of 100 mL. This solution was filtered with a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled into a glass bottle and capped to obtain an internal solution.

(Test example)
Hagerman et al. Reported that protein (bovine serum albumin: BSA) in solution was aggregated by tannin, and the amount of precipitation was proportional to the amount of tannin ( J. Agric . Food . Chem ., 1978, Vol. 26 , 809) . -812). The present inventors have found that when a BSA solution is added to an iron ion solution, the solution is suspended, and the amount of light transmission decreases, and the decrease in the amount of transmission correlates with the concentration of iron ions. And using the property of this iron ion, the present inventors evaluated the astringent taste of the oral solution containing this iron ion using a BSA solution.

(Test method)
1) Preparation of BSA solution 3 g of BSA (Sigma Chemical Co .; fraction V, fatty acid free) is dissolved in an appropriate amount of purified water, 100 mg of citric acid is added, and the pH is adjusted to 4.8 with NaOH solution (1 mol / L). Adjusted to 100 mL with purified water.
2) Preparation of diluted solution 100 mg of citric acid was dissolved in an appropriate amount of water, the pH was adjusted to 4.8 with NaOH solution (1 mol / L), and the solution was made up to 100 mL with purified water.
3) Preparation of iron ion solution To 0.030 g, 0.090 g and 0.150 g of ferrous fumarate, 0.10 g of citric acid was added. Each was dissolved in an appropriate amount of purified water, adjusted to pH 4.8 with NaOH solution (1 mol / L), and made up to 100 mL with purified water.
4) Evaluation of protein-iron ion interaction (convergence) 6 mL of BSA solution was added to 2 mL of each iron ion solution, and the total volume was adjusted to 10 mL with a diluting solution. This was shaken at 40 ° C. for 30 minutes. Using a quartz cell (L = 1 cm), the absorbance at 500 nm, which is a wavelength that is not absorbed by each transparent solution, was measured with a spectrophotometer (manufactured by Hitachi, Ltd .: U-3300).

The results are shown in FIG.
This figure shows that iron ion concentration and absorbance are correlated.
When the absorbance when an iron ion solution containing a certain substance was mixed with a BSA solution decreased compared to the case where no addition was made, the addition of that substance reduced aggregation (convergence) due to protein-iron ion interaction. That is, the astringent taste is reduced. In fact, according to sensory tests, it has been confirmed that absorbance and strength of astringency are correlated.
5) Protein aggregation properties of Examples and Comparative Examples The protein aggregation properties of Examples and Comparative Examples were evaluated by the methods described in 1) to 4) above. The results are shown in Table 1.

Since the light absorbency of an Example is smaller than a corresponding comparative example, it became clear that the protein aggregation property of an Example, ie, an astringent taste, is smaller than a comparative example.

It is useful as an internal liquid composition that suppresses the unpleasant taste (convergence) of iron ions and improves the ingestibility.

It shows the correlation between protein aggregation and iron ion concentration.

Claims (1)

An oral liquid containing divalent iron ions, wherein one or more selected from polyethylene glycol, polyvinyl alcohol and polyvinylpyrrolidone are blended, and the internal liquid having a pH of 2.5 to 7.0 Composition.

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