JPH054921A - Vitamin b-containing oral solution agent - Google Patents

Abstract

PURPOSE:To provide a vitamin B-containing oral solution agent having an improved flavor and not leaving a bitter taste in oral cavities ever after administered. CONSTITUTION:A vitamin B-containing oral solution agent comprising (A) a vitamin B, preferably at least one kind, especially three kinds, selected from thiamine hydrochloride, sodium riboflavin phosphate and pyridoxine hydrochloride, and (B) a saccharide, preferably one or two kinds, especially two kinds, selected from sucrose and maltitol, is compounded with (C) an amino acid, preferably at least one kind selected from sodium aspartate, sodium L-glutamate and glycine, especially sodium L-aspartate, and (D) an apple flavor to provide the objective vitamin B-containing oral solution agent which has a largely improved flavor and which can readily be administered. The ingredients A, B, C and D are used usually in amounts of 0.003-0.33wt.%, 525wt.%, 0.01-0.5wt.% and 0.01-0.5wt.%; preferably 0.003-0.33wt.%, 15-20wt.%, 0.02-0.25wt.% and 0.05-0.wt.%, respectively, based on the total weight of the solution agent.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a vitamin B-containing oral liquid preparation having an improved taste.

[0002]

2. Description of the Related Art It is well known that vitamin B has a bitter taste and is difficult to take. In order to improve this, conventional sucrose (white sugar),
Contains sugars such as honey.

However, even an oral liquid preparation containing the above-mentioned saccharides does not have a good flavor, and bitterness remains in the oral cavity after ingestion, which causes discomfort.

[0004]

An object of the present invention is to provide a vitamin B-containing oral liquid preparation having an improved flavor.

[0005]

[Means for Solving the Problems] The present inventors
As a result of various studies on the improvement of the flavor of the contained oral liquid, it was found that adding amino acid and apple flavor to the liquid consisting of vitamin B and sugar improves the flavor and bitterness does not remain in the oral cavity after the administration. Completed the invention.

Vitamin B as used in the present invention means thiamine,
A pharmaceutically acceptable salt of thiamine (eg, thiamine hydrochloride, thiamine nitrate, etc.), a thiamine derivative (eg,
Thiamine disulfide, thiamine propyl disulfide, etc.), riboflavin, riboflavin derivatives (eg, riboflavin butyrate, riboflavin sodium phosphate, etc.),
One or a mixture of two or more selected from pyridoxine, a pharmaceutically acceptable salt of pyridoxine (eg, pyridoxine hydrochloride, etc.) and a pyridoxine derivative (eg, pyridoxal phosphate, pyridoxamine phosphate, etc.).

The sugar as used in the present invention refers to sugars belonging to 6-carbon sugars (eg glucose, fructose etc.), 2 sugars (eg sucrose, maltose etc.), 5 carbon sugar alcohols (eg xylitol etc.), 6 One or a mixture of two or more selected from carbonic sugar alcohols (eg sorbitol, mannitol etc.), 2 sugar alcohols (eg maltitol etc.) and natural sweeteners containing them (eg honey etc.). .

The amino acid referred to in the present invention is one or more selected from L-aspartic acid, L-glutamic acid, glycine, and pharmaceutically acceptable salts thereof (for example, sodium salt, hydrochloride). Is a mixture of.
Although L-aspartic acid and L-glutamic acid have optical isomers, the present invention also includes these optical isomers and racemates and pharmaceutically acceptable salts thereof.

Of these vitamin B, sugar and amino acid, one or more selected from thiamine hydrochloride, sodium riboflavin phosphate and pyridoxine hydrochloride as vitamin B, and one selected from sucrose and maltitol as sugar. It is particularly preferable to use one kind or two kinds or more as an amino acid, one kind or two or more kinds selected from sodium L-aspartate, sodium L-glutamate and glycine.

In the present invention, the apple flavor is an ester of an aliphatic carboxylic acid contained in apple (for example, isoamyl acetate, ethyl butyrate, isoamyl isovalerate, n-propyl isovalerate), and aliphatic alcohol ( For example,
n-hexyl alcohol), an aliphatic aldehyde (eg, hexyl aldehyde), and one or a mixture of two or more compounds contained in other flavors of apple, which are recovered from apple by a method used in the food industry. The flavors and the flavors containing them as main components are also included.

Commercially available products of these apple flavors are available, for example, Apple Essence RA-7570 and Apple Essence A- from Takasago International Corporation.
70381, Apple Essence A-70382 and Apple Flavor A-90291.

The vitamin B-containing oral liquid preparation of the present invention is produced by adding vitamin B, sugar and amino acid to water and usually dissolving at 70 to 90 ° C., cooling the solution, and then adding an apple flavor and filtering the solution. .

The amount of vitamin B used is usually 0.003 to 0.33% by weight based on the total weight of the oral liquid preparation of the present invention.

The amount of sugar used is usually 5 to 25% by weight, preferably 15 to 20% by weight, based on the total weight of the oral liquid preparation of the present invention.

The amount of the amino acid used is usually 0.01 to 0.5% by weight, preferably 0.1% by weight based on the total weight of the oral liquid preparation of the present invention.
It is from 02 to 0.25% by weight.

The amount of apple-based fragrance used is usually 0.01 to 0.5% by weight, preferably 0.05 to 0.2% by weight, based on the total weight of the oral liquid preparation of the present invention.

The vitamin B-containing oral liquid preparation of the present invention, if necessary, is an organic or inorganic substance usually added to foods and / or pharmaceuticals such as ethanol, acidulants (eg citric acid, malic acid, fumaric acid, tartaric acid, hydrochloric acid, etc.). Acid), preservatives (for example, benzoic acid, sodium benzoate, ethyl paraoxybenzoate, butyl paraoxybenzoate, and the like, which are usually added to foods and / or pharmaceuticals) and Chinese herbs extract (for example, Yokuinin extract, carrot extract). ) Can also be added.

[0018]

EFFECTS OF THE INVENTION The vitamin B-containing oral liquid preparation of the present invention has significantly improved flavor and is easy to take as compared with the conventional vitamin B-containing oral liquid preparation.

The effects of the vitamin B-containing oral liquid preparation of the present invention will be described below with reference to test examples.

Test Example 1 1. Specimen / liquid agent of Examples 1-5 / liquid agent of Comparative Examples 1-4 Test method Liquid formulation of Example and corresponding liquid formulation of Comparative Example (Example 1)
And the solution of Example 2 corresponds to the solution of Comparative Example 1, the solution of Example 3 corresponds to the solution of Comparative Example 2, the solution of Example 4 corresponds to the solution of Comparative Example 3, and The liquid agent of Example 5 corresponds to the liquid agent of Comparative Example 4. ) And a code,
After the panelist did not know what the sample was, 20 panelists (10 boys and 10 girls) randomly selected to take it were subjected to a sensory test by a two-point comparison method. Bengtss is used to test the significance of test results.
On table was used (for the two-point comparison method and its significant difference test, refer to Sensory test method-enlarged version-Junpei Ikeda and Kunisuke Ichikawa, published by Food Science Society of 1967, pp. 3-7).

That is, before oral administration, the mouth was rinsed twice with 50 ml of water, and 5 minutes after that, 30 ml of the sample was swallowed by 2 mouths (about 15 ml and then about 15 ml). Then, as in the above, the oral cavity was rinsed and a sample to be compared was taken. Within 1 minute, the panelists vote which of the two samples to be compared is superior in each evaluation item of scent, sweetness, sourness, bitterness and umami, and which sample is superior in the comprehensive evaluation. Then, the number of people who answered that each item was excellent was tabulated and a significant difference test was conducted.

3. Test Results The results of comparing the liquid preparation of Example 1 and the liquid preparation of Comparative Example 1 are shown in Table 1, the results of the liquid preparation of Example 2 and the liquid preparation of Comparative Example 1 are shown in Table 2, and the liquid preparation of Example 3 are shown. The results of comparison with the liquid preparation of Comparative Example 2 are shown in Table 3, the results of comparison of the liquid preparation of Example 4 and the liquid preparation of Comparative Example 3 are shown in Table 4, and the liquid preparation of Example 5 and the liquid preparation of Comparative Example 4 are shown. The results of the comparison are shown in Table 5.

Each number in Tables 1 to 5 indicates the number of persons who answered that the liquid medicine of the example and the liquid medicine of the comparative example corresponding thereto for each evaluation item were excellent. In addition, the ** mark attached to the numbers in these tables is a significant difference level of 1%, and the * mark is a significant difference level of 5%, which means that the liquid preparations of Examples are superior to the liquid preparations of Comparative Examples.

[0024]

[Table 1]

[0025]

[Table 2]

[0026]

[Table 3]

[0027]

[Table 4]

[0028]

[Table 5] As shown in Tables 1 to 5, it was confirmed that the liquid preparation of the present invention was significantly superior to the liquid preparations of Comparative Examples in all the evaluation items.

[0029]

EXAMPLES The present invention will be described in more detail below with reference to examples and comparative examples.

Example 1 Formulation Sodium riboflavin phosphate 19 mg Pyridoxine hydrochloride 50 mg Sucrose (sucrose) 1500 mg Maltitol 3000 mg L-sodium aspartate 60 mg Sodium benzoate 21 mg Ethyl paraoxybenzoate 2.5 mg Butyl paraoxybenzoate 1.5 mg L-malic acid 90 mg Yokuinin flow extract 2 ml Apple flavor (Apple Essence RA-7570, manufactured by Takasago International Corporation) 30 mg ──────────────────────── ── Total amount of purified water 30ml Manufacturing method Weigh 100 times the amount of each component of the above prescription, about 230
Each component from riboflavin sodium phosphate to Yokuinin flow extract was added to 0 ml, heated and dissolved at about 80 ° C., cooled to room temperature, and then apple flavor was added. Purified water was added to make 3000 ml, and after filtering this, 30 ml
Each was filled in a bottle, and an oral liquid preparation of the present invention containing 19 mg of riboflavin sodium phosphate and 50 mg of pyridoxine hydrochloride in one bottle was obtained.

Example 2 Formulation Sodium riboflavin phosphate 19 mg Pyridoxine hydrochloride 50 mg Sucrose (sucrose) 1500 mg Maltitol 3000 mg L-sodium glutamate 7.5 mg Sodium benzoate 21 mg Ethyl paraoxybenzoate 2.5 mg Butyl paraoxybenzoate 1. 5 mg L-malic acid 90 mg Yokuinin flow extract 2 ml Apple flavor (Apple Essence A-70381, manufactured by Takasago International Corporation) 30 mg ─────────────────────── ── Total amount of purified water 30ml Manufacturing method Weigh 100 times the amount of each component of the above prescription, about 230
Each component from riboflavin sodium phosphate to Yokuinin flow extract was added to 0 ml, heated and dissolved at about 80 ° C., cooled to room temperature, and then apple flavor was added. Purified water was added to make 3000 ml, and after filtering this, 30 ml
Each was filled in a bottle, and an oral liquid preparation of the present invention containing 19 mg of riboflavin sodium phosphate and 50 mg of pyridoxine hydrochloride in one bottle was obtained.

Example 3 Formulation Thiamine hydrochloride 12.5 mg Riboflavin sodium phosphate 19 mg Pyridoxine hydrochloride 25 mg Sucrose (sucrose) 1500 mg Maltitol 3000 mg Glycine 60 mg Sodium benzoate 21 mg Ethyl paraoxybenzoate 2.5 mg Butyl paraoxybenzoate 1 .5 mg L-malic acid 90 mg Apple flavor (Apple Essence A-70382, manufactured by Takasago International Corporation) 30 mg ───────────────────────── water was weighed 100 times the total amount of 30ml manufacturing method above formulation components added, purified water about 230
Each component from thiamine hydrochloride to L-malic acid was added to 0 ml, heated and dissolved at about 80 ° C., cooled to room temperature, and then apple flavor was added. 3000m with purified water
After filtering this, the bottle was filled with 30 ml each, and 1
Thiamine hydrochloride 12.5 mg, riboflavin sodium phosphate 19 mg and pyridoxine hydrochloride 25 m in a bottle
An oral liquid preparation of the present invention containing g was obtained.

Example 4 Formulation Sodium riboflavin phosphate 19 mg Pyridoxine hydrochloride 50 mg Sucrose (sucrose) 1500 mg Maltitol 3000 mg L-sodium aspartate 60 mg Sodium benzoate 21 mg Ethyl paraoxybenzoate 2.3 mg Butyl paraoxybenzoate 1.5 mg DL-malic acid 105 mg Yokuinin flow extract 2 ml Apple-based fragrance (Apple essence RA-7570, manufactured by Takasago International Corporation) 30 mg ───────────────────────── ── Total amount of purified water 30ml Manufacturing method Weigh 100 times the amount of each component of the above prescription, about 230
Each component from riboflavin sodium phosphate to Yokuinin flow extract was added to 0 ml, heated and dissolved at about 80 ° C., cooled to room temperature, and then apple flavor was added. Purified water was added to make 3000 ml, and after filtering this, 30 ml
Each was filled in a bottle, and an oral liquid preparation of the present invention containing 19 mg of riboflavin sodium phosphate and 50 mg of pyridoxine hydrochloride in one bottle was obtained.

Example 5 Formulation Thiamine hydrochloride 12.5 mg Riboflavin sodium phosphate 19 mg Pyridoxine hydrochloride 50 mg Sucrose (sucrose) 1500 mg Maltitol 3000 mg L-sodium aspartate 60 mg L-sodium glutamate 5 mg Sodium benzoate 21 mg Paraoxybenzoic acid Ethyl 2.3 mg Butyl paraoxybenzoate 1.5 mg DL-malic acid 105 mg Yokuinin flow extract 2 ml Apple flavor (Apple flavor A-90291, manufactured by Takasago International Corporation) 30 mg ────────────── ────────────── Add purified water to a total volume of 30 ml Manufacturing method Weigh 100 times the amount of each component of the above formulation, and prepare about 230
Each component from thiamine hydrochloride to Yokuinin flow extract was added to 0 ml, heated and dissolved at about 80 ° C., cooled to room temperature, and then apple flavor was added. Add purified water to 300
After making it 0 ml and filtering this, 30 ml each was filled in a bottle to obtain an oral liquid preparation of the present invention containing 12.5 mg of thiamine hydrochloride, 19 mg of riboflavin sodium phosphate and 50 mg of pyridoxine hydrochloride in one bottle.

Comparative Example 1 Manufacturing method 100 times the amount of each component of the above prescription is weighed and purified water about 230
Each component from riboflavin sodium phosphate to Yokuinin flow extract was added to 0 ml, heated to about 80 ° C. to dissolve, and cooled to room temperature. Purified water was added to make 3000 ml, and after filtering this, 30 ml each was filled in a bottle to obtain an oral liquid preparation of a comparative example containing 19 mg of riboflavin sodium phosphate and 50 mg of pyridoxine hydrochloride in one bottle.

Comparative Example 2 Manufacturing method 100 times the amount of each component of the above prescription is weighed and purified water about 230
Each component from thiamine hydrochloride to L-malic acid was added to 0 ml, heated to about 80 ° C. to dissolve, and cooled to room temperature. Purified water was added to make 3000 ml, and after filtering this,
Fill bottles with 30 ml each, and thiamin hydrochloride 1 in each bottle.
An oral liquid preparation of a comparative example containing 2.5 mg, riboflavin sodium phosphate 19 mg and pyridoxine hydrochloride 25 mg was obtained.

Comparative Example 3 Formulation Sodium riboflavin phosphate 19 mg Pyridoxine hydrochloride 50 mg Sucrose (sucrose) 1500 mg Maltitol 3000 mg Sodium benzoate 21 mg Ethyl paraoxybenzoate 2.3 mg Butyl paraoxybenzoate 1.5 mg DL-malic acid 105 mg Yoquininine Flow extract 2 ml ───────────────────────── Total amount by adding purified water 30 ml Manufacturing method Weigh 100 times the amount of each component of the above formulation and add purified water. About 230
Each component from riboflavin sodium phosphate to Yokuinin flow extract was added to 0 ml, heated to about 80 ° C. to dissolve, and cooled to room temperature. Purified water was added to make 3000 ml, and after filtering this, 30 ml each was filled in a bottle to obtain an oral liquid preparation of a comparative example containing 19 mg of riboflavin sodium phosphate and 50 mg of pyridoxine hydrochloride in one bottle.

Comparative Example 4 Formulation Thiamine hydrochloride 12.5 mg Riboflavin sodium phosphate 19 mg Pyridoxine hydrochloride 50 mg Sucrose (sucrose) 1500 mg Maltitol 3000 mg Sodium benzoate 21 mg Ethyl paraoxybenzoate 2.3 mg Butyl paraoxybenzoate 1.5 mg DL-malic acid 105mg Yokuinin flow extract 2ml ────────────────────────── Total amount of purified water 30ml Manufacturing method 100 times the above formulation Weigh the amount of purified water to about 230
Each component from thiamine hydrochloride to Yokuinin flow extract was added to 0 ml, heated to about 80 ° C. to dissolve, and cooled to room temperature. Purified water was added to make 3000 ml, and after filtering this, 30 ml each was filled in a bottle, and thiamine hydrochloride 12.5 mg and riboflavin sodium phosphate 19 m were placed in one bottle.
g of pyridoxine hydrochloride and 50 mg of pyridoxine hydrochloride were obtained.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Office reference number FI technical display location A61K 47/16 L 7329-4C 47/26 L 7329-4C // (A61K 31/51 31: 525 7252-4C 31:44) 7252-4C

Claims (3)

[Claims] 1. An oral liquid preparation containing vitamin B, which comprises vitamin B, sugar, an amino acid and an apple flavor. 2. One or more kinds selected from thiamine hydrochloride, sodium riboflavin phosphate and pyridoxine hydrochloride as vitamin B, and one or two kinds selected from sucrose and maltitol as sugar.
The oral liquid preparation according to claim 1, wherein one or two or more kinds selected from sodium L-aspartate, sodium L-glutamate and glycine are mixed as amino acids. 3. The oral liquid preparation according to claim 1, wherein thiamine hydrochloride, sodium riboflavin phosphate and pyridoxine hydrochloride are added as vitamin B, sucrose and maltitol are added as sugars, and sodium L-aspartate is added as an amino acid.