JP2006169180A - Copper-containing composition for oral administration - Google Patents

Abstract

The present invention relates to providing a copper-containing composition for oral administration that reduces the astringent taste derived from copper ions, is easy to drink, and does not leave an unpleasant aftertaste.
SOLUTION: One or more copper compounds selected from the group consisting of copper gluconate, copper sulfate, copper citrate, copper chloride, copper nitrate and copper phosphate, and 4 to 20 glycerols are polymerized. It is an ester obtained by condensing polyglycerin and a fatty acid having 8 to 20 carbon atoms, and it is an internal liquid agent containing a polyglycerin fatty acid ester having an HLB of 12 or more and a pH of 2.5 to 7.0. Orally administered composition.
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Description

  The present invention relates to an orally administered composition that reduces the unpleasant taste of a copper compound and improves the feeling of taking.

  The copper-containing composition for oral administration was difficult to drink due to an unpleasant taste derived from copper ions. This taste is the same as the taste when using an astringent that binds to proteins such as tannin and alum. Until now, in order to improve the unpleasant taste of the chemical | medical agent and foodstuff containing a copper compound, the technique which mix | blends an oleoresin and an accent fragrance | flavor is disclosed (patent document 1). However, these are not sufficient in improving the unpleasant taste derived from copper ions.

Japanese Patent Laid-Open No. 01-153622

  An object of the present invention is to provide a copper-containing composition for oral administration that reduces the astringent taste derived from copper 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 extensive studies. As a result, when polyglycerol fatty acid ester is blended with a copper compound, protein aggregation (convergence) due to copper ions is reduced and astringency is improved. As a result, the present invention has been completed.

  That is, the present invention is an orally administered composition comprising a copper compound and a polyglycerin fatty acid ester.

  According to the present invention, it is possible to provide a copper-containing oral administration composition that reduces the astringent taste derived from copper ions, is easy to drink, and does not leave an unpleasant aftertaste.

  The copper compound in the present invention is a salt containing copper and may be either an organic ion or an inorganic ion if the anion is non-toxic. Examples of the organic ion include organic compounds such as gluconic acid, citric acid, and tartaric acid. Examples of acid ions and inorganic ions include sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid, carbonic acid and the like. Examples of the copper compound to be blended include copper gluconate, copper sulfate, copper citrate, copper chloride, copper nitrate, and copper phosphate. These may be blended singly or in combination of two or more.

  The compounding quantity of a copper compound changes with the intended purpose of the copper containing oral administration composition which mix | blends this. From the aspect of nutrition intake, 0.1 to 10 mg per day is preferable in terms of copper ion, and when ingested as a 100 ml oral solution per day, the copper ion concentration is 0.0001 to 0.01 W. / V%.

  The polyglycerol fatty acid ester in the present invention is an ester obtained by condensing polyglycerol obtained by polymerization of 4 to 20 glycerol and a fatty acid having 8 to 20 carbon atoms, and has an HLB of 12 or more. Specifically, decaglycerin monomyristic acid ester, hexaglycerin monomyristic acid ester, decaglycerin monolauric acid ester, hexaglycerin monolauric acid ester, decaglycerin monostearic acid ester, hexaglycerin monostearic acid ester, decaglycerin monocaprylic acid Examples include esters, decaglycerin monooleic acid esters, hexaglycerin monooleic acid esters, decaglycerin monolinolenic acid esters, among which decaglycerin monomyristic acid ester, decaglycerin monostearic acid ester, and decaglycerin monolauric acid ester are preferable. .

  In the copper-containing oral administration composition of the present invention, the polyglycerin fatty acid ester content is 0.1 parts by mass or more, preferably 0, based on 1 part by mass of the copper ion when the copper compound is converted to copper ion. 0.3 to 10000 parts by mass, more preferably 2 to 2000 parts by mass.

  When the copper-containing composition for oral administration of the present invention is used as an internal solution, the pH is adjusted to 2.5 to 7.0, preferably 3.0 to 5.5 in consideration of antiseptic properties and flavor. The pH of the internal solution is, for example, organic acids such as citric acid, malic acid, fumaric acid, tartaric acid, lactic acid, succinic acid, salts of these organic acids, inorganic acids such as phosphoric acid and hydrochloric acid, inorganic acids such as sodium hydroxide, etc. It can be adjusted by adding a base.

  In the copper-containing composition for oral administration of the present invention, vitamins, minerals, amino acids, herbal medicines, herbal extracts, caffeine, royal jelly and the like can be appropriately blended within a range not impairing the effects of the present invention. In addition, additives such as surfactants, antioxidants, colorants, fragrances, flavoring agents, solubilizers, preservatives, and sweeteners can be appropriately blended as necessary so long as the effects of the present invention are not impaired.

  Polyglycerin fatty acid esters have low solubility during storage at low temperatures, and are liable to cause precipitation and floating matters. Therefore, when a crude drug, a crude drug extract, etc. are mix | blended, it is unpreferable to mix | blend polyglycerol fatty acid ester in an internal use liquid agent independently. Therefore, it is possible to mix polyoxyethylene nonionic surfactants and oil components in oral liquids formulated with polyglycerin fatty acid esters to prevent and stabilize the active ingredients such as herbal medicines and herbal extracts. preferable.

  Examples of the oil component include vitamin E, derivatives of vitamin E (for example, esters such as acetic acid and succinic acid), vitamin A, vitamin D, vitamin K, γ-oryzanol, soybean oil, medium chain fatty acid triglyceride, γ-linolenic acid, etc. And triglycerin fatty acid esters. These may be used alone or in combination of two or more. If the blending amount of the oil component is 0.7 parts by mass or less with respect to 1 part by mass of the polyglycerol fatty acid ester, the effect can be obtained. If the oil component is added excessively, the solution will be emulsified and a stable internal solution cannot be obtained.

  The method for preparing the copper-containing oral administration composition of the present invention is not particularly limited. When using it as an internal solution, the purpose is usually to dissolve each component with an appropriate amount of purified water, adjust the pH, adjust the volume by adding the remaining purified water, and filter and sterilize as necessary. A copper-containing composition for oral administration can be obtained.

  Hereinafter, the present invention will be described in more detail with reference to examples and test examples.

Example 1
Copper gluconate 0.004g
Zinc gluconate 0.02g
Polyglycerin fatty acid ester 0.12g
Polyoxyethylene hydrogenated castor oil 0.10g
Tocopherol acetate 0.10g
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
Glycerin 0.10g
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 2
Copper gluconate 0.007g
Zinc gluconate 0.05g
Polyglycerol fatty acid ester 0.10g
Propylene glycol alginate 0.05g
Tocopherol acetate 0.05g
Calcium gluconate 0.80 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
0.12 g of glycerin
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 3
0.03 g of copper gluconate
Zinc gluconate 0.08g
Polyglycerol fatty acid ester 0.20 g
Sucrose fatty acid ester 0.10g
Riboflavin 0.01g
0.01 g of pyridoxine hydrochloride
Ascorbic acid 1.00g
Cyanocobalamin 120μg
Panthenol 0.01g
Nicotinamide 0.05g
Aminoethylsulfonic acid 1.00g
Sorbitol 5.00g
Trehalose 2.00g
Maltitol 2.00g
Citric acid 0.40g
Sodium malate appropriate amount Benzoic acid 0.06g
Butyl paraoxybenzoate 0.006g
Propyl paraoxybenzoate 0.006 g
Tricaprylin 0.05g
Glycerin 0.20g
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 4
Copper gluconate 0.007g
Zinc gluconate 0.05g
Polyglycerol fatty acid ester 0.10g
Polyoxyethylene hydrogenated castor oil 0.07g
Tocopherol acetate 0.02g
Tricaprylin 0.02g
Calcium gluconate 0.80 g
0.01 g of thiamine nitrate
Riboflavin sodium phosphate 0.01 g
0.01 g of pyridoxine hydrochloride
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
Sucralose 0.05g
Citric acid 0.80 g
Sodium citrate appropriate amount Sodium benzoate 0.06g
Butyl paraoxybenzoate 0.006g
Propyl paraoxybenzoate 0.006 g
0.12 g of glycerin
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 5
0.03 g of copper gluconate
Zinc gluconate 0.08g
Polyglycerol fatty acid ester 0.20 g
Polyoxyethylene hydrogenated castor oil 0.10g
Tricaprylin 0.05g
Calcium gluconate 0.40g
Calcium lactate 0.50g
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 0.006g
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.

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 a copper ion solution, the solution is suspended, the amount of light transmitted decreases, and the decrease in the amount of transmission correlates with the concentration of copper ions.

Test method (1) Preparation of BSA solution: 6 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 with NaOH solution (1 mol / L). Adjusted to 4.8 and made up to 100 mL with purified water.

  (2) Preparation of diluting solution: 100 mg of citric acid was dissolved in an appropriate amount of water, pH was adjusted to 4.8 with NaOH solution (1 mol / L), and purified water was adjusted to 100 mL.

  (3) Preparation of copper ion solution: 0.10 g of citric acid was added to 0.02 g, 0.11 g and 0.18 g of copper gluconate. 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-copper ion interaction (convergence) 6 mL of BSA solution was added to 2 mL of each copper ion solution, and the total volume was adjusted to 10 mL with a diluted 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). This result (FIG. 1) shows that the copper ion concentration and the absorbance are correlated.

  Next, it was confirmed that the results of sensory evaluation of the astringent taste of various concentrations of the copper ion solution correlated with the absorbance when the BSA solution was added to the copper ion solution. The sensory evaluation was performed as B when the astringent taste was strongly unacceptable, A4 to A1 according to the strength of the astringent taste, and A when the astringent taste was not felt at all.

  The results are shown in FIG. When the absorbance was about 0.3 or less, it was felt that the astringent taste was sufficiently suppressed. From this, if the absorbance when a copper ion solution added with a certain substance is mixed with a BSA solution is reduced as compared with the case where no addition is made, the addition of that substance causes aggregation due to protein-copper ion interaction ( This means that the (convergence) has decreased, that is, the astringency has decreased.

(5) Protein aggregation properties of specimens Protein aggregation properties of the formulations shown in Table 1 were evaluated by the methods described in (1) to (4) above. The results are also shown in Table 1.

  From Table 1, it can be seen that the absorbance of Sample 1 and Sample 2 blended with polyglycerol fatty acid ester is smaller than the corresponding Sample 3. From this result, it became clear that the protein aggregation derived from copper ions, that is, the astringent taste can be reduced by blending the polyglycerol fatty acid ester.

The correlation between protein aggregation and copper ion concentration is shown. The correlation between the suspension (protein aggregation) generated when a BSA solution is added to a copper ion solution and the result of sensory evaluation of the copper ion solution is shown.

The copper-containing composition for oral administration of the present invention can be applied, for example, to various preparations including pharmaceuticals such as syrups and drinks and quasi-drugs and various beverages such as nutritional functional foods.

Claims (5)

  An oral administration composition comprising a copper compound and a polyglycerol fatty acid ester.   The composition for oral administration according to claim 1, wherein the copper compound is one or more copper compounds selected from the group consisting of copper gluconate, copper sulfate, copper citrate, copper chloride, copper nitrate and copper phosphate. object.   The oral administration according to claim 1 or 2, wherein the polyglycerol fatty acid ester is an ester obtained by condensing polyglycerol obtained by polymerization of 4 to 20 glycerol and a fatty acid having 8 to 20 carbon atoms, and has an HLB of 12 or more. Composition.   The composition for oral administration according to any one of claims 1 to 3, wherein the composition is an internal solution having a pH of 2.5 to 7.0. A method for reducing an unpleasant taste of a copper compound-containing oral administration composition, which comprises blending a polyglycerol fatty acid ester.

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