JP2002080347A - Oral liquid medicine formulated with iron compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oral liquid medicine, formulated with an iron compound, constituted so that unpleasant rust taste derived from a divalent iron ion is suppressed, having good dosing property. SOLUTION: This oral liquid medicine is obtained by formulating a divalent iron ion with a nonionic surfactant in an amount enough to moderate rust taste derived from the iron ion.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to an oral solution containing an iron compound. More specifically, the present invention relates to an internal liquid formulation containing an iron compound, which suppresses the rust taste derived from divalent iron ions and has good ingestibility, and can be applied to the fields of medicine and food.

[0002]

2. Description of the Related Art Conventionally, it has been known that divalent iron ions have better absorbability than trivalent iron ions. However, divalent iron ions have an unpleasant rust, When an oral solution is prepared by mixing iron ions, there has been a problem that the ingestibility is significantly deteriorated.

As a technique for improving the rust taste derived from divalent iron ions, a method of forming an iron (II) -sugar (squarate, fructate) -carboxylate complex (Japanese Patent Application Laid-Open No. 2-72843) and the like are disclosed. However, it was not enough to mask the rust derived from divalent iron ions.

[0004]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an internal compound liquid containing an iron compound, which can suppress unpleasant rust due to divalent iron ions and has good ingestibility.

[0005]

Means for Solving the Problems In order to solve the above-mentioned problems, the present inventors have conducted intensive studies, and as a result, by adding a nonionic surfactant to divalent iron ions, the divalent iron ions are mixed. The present inventors have found that an oral liquid preparation having good ingestibility can be obtained while suppressing the unpleasant rust taste derived from it, and completed the present invention.
That is, the present invention is an internally-administered liquid formulation containing a bivalent iron ion and a nonionic surfactant in an amount sufficient to reduce rustiness derived from the iron ion.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The divalent iron ion in the present invention is an iron ion generated when a divalent iron compound is dissolved in an aqueous solution, or a divalent iron compound formed by dissolving a trivalent iron compound in an aqueous solution. This is the iron ion generated when trivalent iron ions are reduced. As the iron compound to be blended, a bivalent iron compound is preferable, and examples thereof include ferrous fumarate, ferrous sulfate, and sodium iron citrate. These may be used alone or in combination of two or more. When a trivalent iron compound is added,
A trivalent iron ion may be reduced to a divalent iron ion with a reducing substance (for example, a reducing sugar or a reducing organic acid such as ascorbic acid). Thereby, the absorbability from the digestive tract can be improved. The amount of the divalent iron ion in the present invention can be appropriately selected and used according to the purpose. In terms of nutritional intake, the amount is preferably 0.5 to 60 mg per day in terms of iron ions in the iron compound, for example, 0.0005 to 0.06 W / V% in terms of 100 mL.

The nonionic surfactant used in the present invention comprises:
For example, polyoxyethylene hydrogenated castor oil, polyglycerin fatty acid ester, polyoxyethylene polyoxypropylene glycol, sucrose fatty acid ester, glycerin fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin Fatty acid esters, polyethylene glycol fatty acid esters, polyoxyethylene castor oil and the like can be mentioned. Among these nonionic surfactants, polyoxyethylene hydrogenated castor oil, polyglycerin fatty acid ester and sucrose fatty acid ester are particularly preferable in view of the flavor of the surfactant.

The polyoxyethylene hydrogenated castor oil used in the present invention includes, for example, HCO- by Nikko Chemicals.
60, HCO-50, HCO-30 and the like.

The polyglycerin fatty acid ester used in the present invention includes decaglycerin monomyristate, hexaglycerin monomyristate, decaglycerin monolaurate, hexaglycerin monolaurate, decaglycerin monostearate, hexaglycerin Monostearic acid ester, decaglycerin monocaprylic acid ester, decaglycerin monooleic acid ester, hexaglycerin monooleic acid ester, decaglycerin monolinolenic acid ester, and the like are preferable. Esters and decaglycerin monolaurate are particularly preferred. Specifically, DECAGLYN 1-M, DECAGLYN 1-S, DECAGLYN 1-L manufactured by Nikko Chemicals Co., Ltd., Sunsoft Q-14S manufactured by Taiyo Chemical Co., Ltd., ML750 manufactured by Sakamoto Pharmaceutical Co., Ltd.
And the like.

The sucrose fatty acid ester used in the present invention includes sucrose stearate, sucrose palmitate, sucrose oleate, sucrose laurate, sucrose behenate, sucrose erucate. And the like. Among them, sucrose stearate, sucrose palmitate, and sucrose laurate are preferred. Specifically, Ryoto Sugar Ester S-167 manufactured by Mitsubishi Chemical Foods Corporation
0, P-1670, L-1695, Sunsoft S manufactured by Taiyo Chemical Co., Ltd.
E-16, SE-16P and the like.

In the liquid preparation of the present invention, the amount of the nonionic surfactant is sufficient to reduce the rustiness derived from iron ions, and is 0.1 parts by weight or more per 1 part by weight of iron ions. The desired effect is exhibited by blending. However,
Some nonionic surfactants have a peculiar odor and also have a problem of solubility.
% As an upper limit.

The oral liquid preparation of the present invention may further contain a reducing substance. The reducing substance is a reducing sugar such as fructose, glucose and sucrose, and a reducing organic acid such as ascorbic acid (including salts) and erythorbic acid (including salts). These may be used alone or in combination of two or more. The compounding amount of the reducing substance can be appropriately selected according to the purpose, and when trivalent iron is added, it may be at least an amount sufficient to be reduced to divalent iron.

[0013] In the present invention, furthermore, fruit flavors,
The effect of the present invention can be enhanced by blending at least one selected from mint flavors, Western liquor flavors, and milk flavors. Fruit flavors include blueberries, cherries, grapes, plums, etc. Among them, blueberries, cranberries, cassis,
It is preferable to use one or more of aroma, grape, and prune-like flavors. These fragrances are obtained by conventional methods such as extraction, and are used as such, or those obtained by isolating the components or mixing two or more of the isolated components. It is also possible to use. Mint flavors include Japanese peppermint, peppermint, spearmint and the like. These fragrances are obtained by conventional methods such as extraction, and are used as such, or those obtained by isolating the components or mixing two or more of the isolated components. It is also possible to use. Examples of the liquor-based flavor include brown liquor-based and liqueur-based flavors, and preferably include one or more flavors such as brandy, gin, whiskey, curacao, and fruit liqueur. These fragrances are obtained by conventional methods such as extraction, and are used as such, or those obtained by isolating the components or mixing two or more of the isolated components. It is also possible to use. The milk-based flavor includes milk-based, butter-based, and cheese-based flavors, and preferably includes one or more flavors such as milk, condensed milk, powdered milk, cream, butter, cheese, and fermented milk. These fragrances are obtained by conventional methods such as extraction, and are used as such, or those obtained by isolating the components or mixing two or more of the isolated components. It is also possible to use.

The amount of each fragrance is 0.001 of the whole liquid.
-0.5 W / V% is preferable. Further, the above-mentioned fruit-based flavors, mint-based flavors, Western liquor-based flavors, milk-based flavors and other flavors may be mixed and used. As other fragrances, natural juices and the like can also be blended.

[0015] The pH of the oral solution according to the present invention is 2.5.
To 7.0, and preferably 3.0 to 5.5. pH
In the acidic range of less than 2.5, the acidity is too strong to be desirable in terms of ingestibility, and in the basic range where the pH exceeds 7.0, iron ions precipitate as iron hydroxide and precipitate. Therefore, in order to maintain the pH of the liquid medicine for internal use of the present invention in the above-mentioned range, a pH adjuster is added as needed. Examples of the pH adjuster include organic acids such as citric acid, malic acid, fumaric acid, tartaric acid, lactic acid, and succinic acid and salts thereof, inorganic acids such as hydrochloric acid, and inorganic bases such as sodium hydroxide.

The oral liquid preparation of the present invention contains other components such as vitamins, other minerals, amino acids and salts thereof, crude drugs, crude drug extracts, caffeine, royal jelly and the like as far as the effects of the present invention are not impaired. Can be blended.

Further, if necessary, an antioxidant, a coloring agent,
Additives such as flavors, flavoring agents, surfactants, solubilizers, preservatives, and sweeteners can be appropriately blended within a range that does not impair the effects of the present invention.

The oral solution of the present invention can be prepared by a conventional method, and the method is not particularly limited.
Usually, the components are obtained by dissolving each component with an appropriate amount of purified water, adjusting the pH, adjusting the volume by adding the remaining purified water, and filtering and sterilizing as necessary. The oral liquid preparation of the present invention can be applied to various preparations such as pharmaceuticals such as syrups and drinks, quasi-drugs, and various drinks such as health drinks.

[0019]

Industrial Applicability According to the present invention, it has become possible to provide an internal liquid formulation containing an iron compound, which suppresses unpleasant rustiness derived from divalent iron ions and has good ingestibility.

[0020]

The present invention will be specifically described below with reference to examples and test examples.

Example 1 Ferrous fumarate 0.06 g Polyoxyethylene hydrogenated castor oil 1.00 g Sucrose 13.00 g Citric acid 0.60 g Sodium hydroxide Appropriate amount After dissolving the above components in purified water, the pH was adjusted to 3 The solution was adjusted to .5, and purified water was added to make the total volume 100 mL. The solution was filled in a glass bottle, capped, and an oral solution was obtained.

Example 2 Ferrous fumarate 0.06 g Polyglycerin fatty acid ester 0.50 g Sucrose 13.00 g Citric acid 0.60 g Sodium hydroxide Appropriate amount After dissolving the above components in purified water, the pH was adjusted to 3.5. And purified water was added to make a total volume of 100 mL. The solution was filled in a glass bottle and capped to obtain an oral solution.

Example 3 Ferrous fumarate 0.06 g Polyethylene hardened castor oil 0.10 g Polyglycerin fatty acid ester 0.10 g Sucrose 13.00 g Citric acid 0.60 g Sodium hydroxide Appropriate amount The above components were dissolved in purified water. Thereafter, the pH was adjusted to 3.5, purified water was added to make the total volume 100 mL, and the mixture was filled in a glass bottle and capped to obtain an oral solution.

Example 4 Ferrous fumarate 0.06 g Sucrose fatty acid ester 0.50 g Sucrose 10.00 g Citric acid 0.20 g Sodium hydroxide Appropriate amount After the above components were dissolved in purified water, the pH was adjusted to 4.5. And purified water was added to make a total volume of 100 mL. The solution was filled in a glass bottle and capped to obtain an oral solution.

Example 5 Ferrous fumarate 0.06 g Polyglycerin fatty acid ester 0.10 g Polyoxyethylene hydrogenated castor oil 0.10 g Sucrose 13.00 g Citric acid 0.60 g Sodium hydroxide Appropriate amount Blueberry flavor 0.07 g Peppermint Flavor 0.03 g After dissolving the above components in purified water, the pH was adjusted to 3.5, purified water was added to make the total volume 100 mL, and the mixture was filled in a glass bottle and capped to obtain an internal liquid solution.

Example 6 Ferrous fumarate 0.06 g Polyglycerin fatty acid ester 0.10 g Polyethylene hardened castor oil 0.10 g Sucrose 13.00 g Citric acid 0.60 g Sodium hydroxide Appropriate amount Aceroflavor 0.06 g Brandy flavor 0 0.03 g Butter flavor 0.01 g After dissolving the above components in purified water, the pH was adjusted to 3.5, purified water was added to make the total amount 100 mL, and the mixture was filled in a glass bottle and capped to obtain an oral solution.

Comparative Example 1 Ferrous fumarate 0.06 g Sucrose 13.00 g Citric acid 0.60 g Sodium hydroxide Appropriate amount After the above components were dissolved in purified water, the pH was adjusted to 3.5 and purified water was added. In addition, the total amount was adjusted to 100 mL, filled in a glass bottle, and capped to obtain an oral liquid preparation.

Test Example [Evaluation of flavor related to iron rust] Using the seven types of Examples 1 to 6 and Comparative Example 1 as test liquids, the flavor evaluation related to the iron rust of each oral solution was evaluated according to the following evaluation methods and evaluation criteria. Carried out.

<Test Method> Women 10 to 25 to 40 years old
Taking 10 mL of the test solution with a person as a panel, the iron rust was evaluated. After evaluating one sample, the mouth was rinsed with warm water, and after 30 minutes or more, the next test solution was evaluated.

<Evaluation Criteria> Iron rust does not taste 1 point Iron rust taste hardly 2 points Iron rust taste is moderate 3 points Iron rust taste 4 points Iron rust taste is somewhat strong 5 points The taste of iron rust is quite strong. 6 points <Results> The results were obtained as average values and are shown in Table 1. As is evident from Table 1, Examples 1 to 6 exhibited excellent ingestibility with suppressed unpleasant rust derived from divalent iron.

[0031]

[Table 1]

Example 7 Ferrous fumarate 0.06 g Polyoxyethylene hydrogenated castor oil 1.00 g Citric acid 0.60 g Sodium hydroxide Appropriate amount After the above components were dissolved in purified water, the pH was adjusted to 3.5. , Purified water was added to make the total amount 100 mL, and the mixture was filled in a glass bottle and capped to obtain an oral solution.

Example 8 Ferrous fumarate 0.06 g Sucrose fatty acid ester 0.50 g Citric acid 0.20 g Sodium hydroxide Appropriate amount After the above components were dissolved in purified water, the pH was adjusted to 4.5 and purified. Water was added to make the total volume 100 mL, and the mixture was filled in a glass bottle and capped to obtain an oral liquid preparation.

Example 9 Ferrous fumarate 0.06 g Polyoxyethylene hydrogenated castor oil 0.10 g Polyglycerin fatty acid ester 0.20 g Thiamine nitrate 0.01 g g Riboflavin sodium phosphate 0.01 g Pyridoxine hydrochloride 0.01 g Tocopherol acetate 0 .10 g Ascorbic acid 1.00 g Aminoethyl sulfonic acid 2.00 g Sucrose 10.00 g Trehalose 10.00 g Erythritol 3.00 g Citric acid 0.60 g Sodium citrate qs Sodium benzoate 0.06 g Glycerin 0.20 g Aceroflavor 05g Blueberry flavor 0.05g After the above components were dissolved in purified water, the pH was adjusted to 3.0, and purified water was added to bring the total volume to 100 mL. This solution was filtered through a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled in a glass bottle and capped to obtain an oral solution.

Example 10 Ferrous Fumarate 0.06 g Polyoxyethylene hydrogenated castor oil 0.10 g Polyglycerin fatty acid ester 0.30 g Calcium gluconate 2.00 g Magnesium aspartate 1.00 g Thiamine nitrate 0.01 g Riboflavin 0.1 g 01 g pyridoxine hydrochloride 0.10 g tocopherol acetate 0.10 g ascorbic acid 1.00 g aminoethylsulfonic acid 1.00 g sucrose 8.00 g trehalose 10.00 g xylitol 7.00 g stevia extract 0.03 g malic acid 0.10 g citric acid 0 .40g Sodium citrate qs 0.06g butyl parahydroxybenzoate 0.006g propyl paraoxybenzoate 0.006g glycerin 0.20g prune flavor 0.07g peppermint flavor 0.03g above After dissolving the minutes in purified water, the pH was adjusted to 4.0, and the total volume was adjusted to 100mL by adding purified water. This solution was filtered through a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled in a glass bottle and capped to obtain an oral solution.

Example 11 Ferrous fumarate 0.06 g Polyoxyethylene hydrogenated castor oil 0.10 g Polyglycerin fatty acid ester 0.20 g Sucrose fatty acid ester 0.10 g Riboflavin 0.01 g Pyridoxine hydrochloride 0.01 g Tocopherol acetate 0.1 20 g ascorbic acid 1.00 g cyanocobalamin 120 μg panthenol 0.01 g nicotinamide 0.05 g aminoethylsulfonic acid 1.00 g sucrose 10.00 g trehalose 6.00 g maltitol 5.00 g indigestible dextrin 5.00 g citric acid 0 .20 g Sodium malate qs 0.06 g butyl parahydroxybenzoate 0.006 g propyl paraoxybenzoate 0.006 g glycerin 0.20 g potassium sorbate 0.06 g grape flavor 0.07 g After the above components were dissolved in purified water, the pH was adjusted to 4.5, and purified water was added to make a total volume of 100 mL. This solution was filtered through a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled in a glass bottle and capped to obtain an oral solution.

Example 12 Ferrous Fumarate 0.06 g Polyoxyethylene hydrogenated castor oil 0.10 g Polyglycerin fatty acid ester 0.30 g Calcium gluconate 0.80 g Magnesium aspartate 0.40 g Thiamine nitrate 0.01 g Riboflavin phosphate Sodium 0.01 g Pyridoxine hydrochloride 0.01 g Tocopherol acetate 0.10 g Ascorbic acid 1.00 g Nicotinamide 0.10 g Caffeine anhydride 0.10 g Aminoethylsulfonic acid 2.00 g Yoquinin flow extract 2.00 m Sucrose 10.00 g Trehalose 10.00g Maltitol 5.00g Indigestible dextrin 5.00g Citric acid 0.60g Sodium citrate qs Sodium benzoate 0.06g Glycerin 0.20g Butyl parahydroxybenzoate 0.006g Paraoxo After dissolving the benzoate propyl 0.006g acerola flavor 0.05g blueberry flavor 0.05g The above ingredients in purified water, the pH was adjusted to 3.5, the total amount of purified water was added to a 100 mL. This solution was filtered through a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled in a glass bottle and capped to obtain an oral solution.

Example 13 Ferrous fumarate 0.06 g Polyglycerin fatty acid ester 0.40 g Calcium gluconate 2.00 g Magnesium aspartate 1.00 g Thiamine nitrate 0.011 g Riboflavin sodium phosphate 0.02 g Pyridoxine hydrochloride 0.03 g Tocopherol acetate 0.10 g Ascorbic acid 1.00 g Nicotinamide 0.05 g Caffeic anhydride 0.10 g Aminoethylsulfonic acid 2.00 g Yokuinin flow extract 2.00 m Royal jelly 0.60 g Sucrose 10.00 g Trehalose 10.00 g Dextrose 10 0.000 g Stevia extract 0.05 g Citric acid 0.60 g Sodium citrate qs Sodium benzoate 0.06 g Glycerin 0.20 g Butyl parahydroxybenzoate 0.006 g Propyl paraoxybenzoate 0.06 g After dissolving 6g of potassium sorbate 0.06g blackcurrant flavor 0.07g gin flavor 0.03g The above ingredients in purified water, the pH was adjusted to 3.5, the total amount of purified water was added to a 100 mL. This solution was filtered through a filter paper, and the filtrate was sterilized by heating at 80 ° C. for 25 minutes using a sterilizer, and then filled in a glass bottle and capped to obtain an oral solution.

In Examples 7 to 11, the unpleasant rust derived from divalent iron ions was suppressed, and the ingestion was good.

Claims (6)

[Claims] 1. An oral liquid preparation containing a divalent iron ion and a nonionic surfactant in an amount sufficient to reduce rustiness derived from the iron ion. 2. The oral liquid preparation according to claim 1, wherein the nonionic surfactant is one or more selected from the group consisting of polyoxyethylene hydrogenated castor oil, polyglycerin fatty acid ester, and sucrose fatty acid ester. 3. The oral liquid preparation according to claim 1, further comprising a reducing substance. 4. The oral liquid preparation according to claim 3, wherein the reducing substance is a reducing sugar or a reducing organic acid. 5. A fruit flavor, a mint flavor,
The oral liquid preparation according to claim 3, wherein at least one selected from a Western liquor flavor and a milk flavor is blended. 6. The method according to claim 1, wherein the pH is 2.5 to 7.0.
The oral liquid preparation according to any one of the above.