KR20100073987A - Liquid preparation reducing unpleasant taste and bad smell - Google Patents

Abstract

PURPOSE: An internal medicine containing vitamin B1 of which unpleasant taste and smell are reduced is provided to ensure pharcological action and to use as soft drink and non-medical supplies. CONSTITUTION: An internal medicine contains vitamin B1 of which unpleasant taste and smell are reduced. The vitamin B1 includes thiamine, thiamine nitrate, thiamine sulfide nitrae(bithiamine nitrate), thiamine sulfide, thiamine di cetyl sulfate salt, dicethiamine hydrochloride, fursultiamine hydrochloride, and fursultiamine. The internal medicine contains water, ethanol, propylene glycol, or glycerin.

Description

LIQUID PREPARATION REDUCING UNPLEASANT TASTE AND BAD SMELL}

The present invention relates to an oral solution having reduced unpleasant taste and odor derived from vitamin B ₁ .

Drugs often exhibit unpleasant tastes such as bitterness, astringent taste, or astringent taste, and many of them cannot be taken as they are. In addition, there are many unpleasant odors inherent in the drug, and therefore, many people feel unpleasant at the time of taking it. Therefore, it is necessary to reduce unpleasant taste and smell in the oral cavity at the time of taking.

Vitamin B ₁ is a useful drug that is widely used as an oral solution for foods, health foods, specific nutritional foods, quasi-drugs, new quasi-drugs, and medicines. However, vitamin B ₁ is an active substance for quasi-drugs, quasi-drugs, and medicines, and when used as a high concentration oral solution, it becomes more unpleasant such as bitterness, astringent taste, and arine taste. Since an unpleasant smell also arises, there was a fault that it was difficult to take.

In order to reduce the unpleasant taste and smell of vitamin B ₁ and to make it easy to take, various methods have been tried conventionally, for example, the method of mix | blending the gluconate and the calcium salt of an organic acid (patent document 1), A method of blending a flute-based perfume, acesulfame potassium and a stevia extract (Patent Document 2), a method using electrolytic reduced water obtained by electrolyzing an electrolyte (Patent Document 3), and a method of reducing the bitter taste by adding a telephone liquid sugar ( Patent document 4) and the method (patent document 5) which contain at least 1 sort (s) of menthol and polyoxyethylene polyoxy propylene glycol are known.

However, having the masking method of the unpleasant taste and odor derived from vitamin B ₁ in so far masking the unpleasant taste of a low concentration of vitamin B ₁ which may be, reduced function of the unpleasant taste of high concentrations of vitamin B ₁ is satisfied It wasn't.

In addition, especially in an oral solution containing a high concentration of vitamin B ₁ , not only the unpleasant taste is strong, but also because the thiamine odor derived from vitamin B ₁ is strongly felt when the formulation is a liquid, there is a problem that the taking of the oral solution is extremely bad. there was.

[Patent Document 1] Japanese Patent Publication No. 2003-335679

[Patent Document 2] Japanese Patent Publication No. 2003-231647

[Patent Document 3] Japanese Patent Application Laid-Open No. 2002-338498

[Patent Document 4] Japanese Unexamined Patent Publication No. 2002-322062

[Patent Document 5] Japanese Patent Application Laid-Open No. 11-139992

Accordingly, an object of the present invention is to provide oral aekjeeul which contains a high concentration, and the unpleasant taste of vitamin B ₁ is a reduced odor originating from the vitamin B _1.

The present inventors have found that the result of various investigations to solve the above problems, can be by blending the carbon dioxide a certain amount of the oral solution, effectively reducing the unpleasant taste and odor attributable to the high concentration of vitamin B _1, the present invention Came to complete.

That is, the present invention provides an oral solution having an unpleasant taste and odor derived from vitamin B ₁ containing ₁ μg / mL or more of vitamin B ₁ and 1.0 to 4.0 kg / cm 3 of carbon dioxide at a gas internal pressure.

In addition, the present invention relates to an unpleasant taste and odor derived from vitamin B ₁ of the vitamin B ₁ oral solution which contains 1.0 to 4.0 kg / cm 3 of carbon dioxide in an internal oral solution containing ₁ μg / mL or more of vitamin B. It is to provide a reduction method.

According to the present invention, it is possible to reduce the unpleasant taste and odor derived from vitamin B ₁ in oral liquid preparation that contains a high concentration of vitamin B _1. Therefore, the oral solution of the present invention is useful as a soft drink, quasi-drugs, and especially medicines in order to have an excellent feeling of taking and pharmacological action of vitamin B ₁ .

In the present invention, as vitamin B ₁ , for example, thiamin, thiamin hydrochloride, thiamin nitrate, thiamin disulfide nitrate (bistiamine nitrate), thiamin disulfide, thiamin disetyl sulfate ester salt, disetiamine hydrochloride, fursulthiamine hydrochloride, green Description thiamine, loam thiamine, Shiko thiamine, biseuyi portion thiamine, bis Ben thiamine, Pro alcohol thiamine, benpo thiamine, Coca decarboxylase, dibenzoyl one or both of thiamine vitamin B ₁ and selected from the salts and derivatives of The above is mentioned.

In the present invention, the content of vitamin B ₁ is ₁ µg / mL or more with respect to the entire oral solution, but 10-800 µg / mL is preferable, 25-800 µg / mL is more preferable, and 45-200 µg / mL Is more preferable.

In the present invention, carbon dioxide may be used alone as carbon dioxide, or two or more types of gas such as oxygen, hydrogen, and nitrogen other than carbon dioxide may be mixed, but carbon dioxide is preferably used alone.

In the present invention, the carbon dioxide content is 1.0 to 4.0 kg / cm 3 as the gas internal pressure (amount of gas dissolved in the unit volume) with respect to the entire internal liquid, but 2.2 to 3.7 kg / cm 3 is preferable, and 2.5 to 3.5 kg / cm 3 Is more preferable, and 3.0-3.4 kg / cm <3> is further more preferable.

If the gas internal pressure is less than 1.0 kg / cm 3, it is not preferable in that an unpleasant taste or smell reduction effect derived from vitamin B ₁ cannot be sufficiently obtained.

Water, ethanol, propylene glycol, glycerin are mentioned as a solvent of the internal liquid solution of this invention. Among these, it is preferable to use water.

-오리자놀, 이노시톨,

-리포산, 비오틴, 엽산, 우르소데스옥시콜인산, 로얄제리, 아스파라긴산 나트륨, 글루크로노락톤, 첨가제 등을 소망에 따라 배합할 수 있다.In addition, the oral solution of the present invention includes vitamin B ₁ and carbon dioxide, as well as components that can be blended with common oral solutions, for example, vitamin B ₂ , niacin, pantothenic acid, vitamin B ₆ , vitamin B ₁₂ , vitamin C, and the like. Vitamins; taurine; amino acids such as carnitine chloride, cysteine; herbals, caffeine, minerals such as dichloroacetic diisopropylamine, iron, calcium; chondroitin, glucosamine,

-Oryzanol, inositol,

Lipoic acid, biotin, folic acid, ursodesoxycholic acid, royal jelly, sodium aspartic acid, glucronolactone, and additives can be blended as desired.

Examples of the vitamin B ₂ include one or two or more selected from vitamin B ₂ and salts thereof, such as riboflavin, riboflavin butyrate, sodium riboflavin phosphate and flavin adenine dinucleotide, and salts thereof. The content of vitamin B ₂ was a 20 ~ 240㎍ / mL is preferred.

As said niacin, 1 type, or 2 or more types chosen from niacin, such as nicotinic acid, nicotinic acid amide, inositol hexanicotinate, hepronicate, its salt, and derivatives thereof, is mentioned, for example. As for content of niacin, 120 micrograms / mL-6 mg / mL are preferable.

Examples of the pantothenic acid include one or two or more selected from pantothenic acid such as calcium pantothenate, sodium pantothenate, panthenol and panthetin, salts thereof and derivatives thereof. As for content of pantothenic acid, 50 microgram / mL-3 mg / mL are preferable.

Examples of the vitamin B ₆ include one or two or more selected from vitamin B ₆ and salts thereof and derivatives thereof such as pyridoxine, pyridoxal, pyridoxamine, pyridoxyl phosphate, pyridoxal phosphate, and pyridoxamine phosphate. Can be mentioned. The content of the vitamin B ₆ is 20㎍ / mL ~ 1mg / mL is preferred.

Examples of the vitamin B ₁₂ include one or two or more selected from vitamin B ₁₂ and salts thereof, such as cobalamin, cyanocobalamin, hydroxylcobalamin, hydroxycobalamin acetate, and mecobalamin and derivatives thereof. have. The content of vitamin B ₁₂ is the 0.01 ~ 6㎍ / mL is preferred.

As an additive, a mating agent, a sweetener, a stabilizer, a thickener, a dissolution aid, a pH adjuster, a coloring agent, a fragrance, etc. are mentioned, for example.

As said mating agent, for example, povidone, menthol, disodium glycyric acid, maleic acid, sodium maleate, tartaric acid, sodium tartarate, succinic acid, sodium succinate, acetic acid, glutamic acid, sodium glutamate, citric acid, sodium citrate, gluconolactone, sodium chloride Etc. can be mentioned.

As the sweetener, for example, sucrose, fructose, glucose, lactose, sorbitol, multitol, erythritol, xylitol, trehalose, sucralose, honey, saccharin, sodium saccharin, stevia extract, aspartame, acesulfame potassium, black candy, beef Martin, licorice, etc. are mentioned.

As said stabilizer, povidone, glycerin, erythorbic acid and its salt, edetic acid and its salt, metaphosphoric acid, etc. are mentioned, for example.

Examples of the thickener include sodium carmellose, agar, povidone, polyvinyl alcohol, xanthan gum, and the like.

Examples of the dissolution aid include polysorbate, macrogol, polyoxyethylene hardened castor oil, povidone, sodium hydroxide and the like.

Examples of the pH adjusting agent include citric acid, sodium citrate, lactic acid, sodium hydroxide, hydrochloric acid, maleic acid, sodium maleate, tartaric acid, sodium tartarate, succinic acid, sodium succinate, acetic acid, gluconic acid, and phosphoric acid.

As said coloring agent, a tar pigment, iron trioxide, a caramel, etc. are mentioned, for example.

Examples of the flavors include apple tea flavor, apricot flavor, rose tea flavor, black tea flavor, apple flavor, pineapple flavor and the like.

In that it ensures the stability of the pharmacological effects of vitamin B ₁ as the pH of the oral solution of the present invention, pH1 ~ 6 are preferable, and more preferably in the range of pH2.0 ~ 4.5. pH adjustment may be performed by a conventionally well-known method, for example by addition of an acid or a base.

The oral solution of the present invention can be produced according to the method for producing an oral solution of the conventional method.

The internal oral solution of the present invention can be taken in the same manner as a normal liquid.

EXAMPLE

Hereinafter, although an Example is given and this invention is demonstrated in more detail, the scope of the present invention is not limited to this.

Preparation Example 1 Preparation of oral solution and comparative solution containing vitamin B ₁

0.4 g, 1 g, 2 g, and 10 g of vitamin B ₁ (nitrate) were dissolved in 40 L of purified water and degassed.

Next, 8 L of each of the obtained solutions or deaerated purified water was taken into a pressure-resistant container, and carbon dioxide was adjusted to be 1.2 kg / cm 3, 2.2 kg / cm 3, and 3.2 kg / cm 3 with a gas internal pressure, respectively. . This liquid was filled in the washed brown glass bottle, and what was capped was made into the oral solution.

Test Example 1

Five normal subjects put about 5 mL of the oral solution of the preparation example or the comparative solution into the mouth, and spit out after about 15 seconds by spreading it on the tongue while being careful not to swallow. At this time, it evaluated in five stages which show the degree of unpleasant taste and unpleasant smell, such as astringent, irritation, bitterness, astringent taste, and astringency, at the time.

flavor

1: We feel very unpleasant taste

2: We feel unpleasant taste

3: We feel unpleasant taste a little

4: We feel like feeling unpleasant taste

5: I do not feel anything

smell

1: We feel very unpleasant smell

2: We feel unpleasant smell

3: We feel unpleasant smell a little

4: We feel like feeling unpleasant smell

5: I do not feel anything

Table 1 shows the evaluation of the taste of the oral solution containing vitamin B ₁ and Table 2 shows the evaluation of the smell.

TABLE 1

Vitamin B ₁ (㎍ / mL)     0     10    25     50    250
CO ₂ (kg / cm 3)

     0    5.0     2.4    1.8     1.4    1.2     1.2    5.0     4.6    2.8     2.2    2.0     2.2    5.0     4.8    4.0     4.2    4.0     3.2    5.0     4.8    4.6     4.6    4.2

 TABLE 2

Vitamin B ₁ (㎍ / mL)     0     10    25     50    250
CO ₂ (kg / cm 3)

     0    5.0     1.8    1.4     1.2    1.0     1.2    5.0     3.0    2.8     1.8    1.4     2.2    5.0     4.2    4.0     3.6    3.4     3.2    5.0     4.4    4.2     4.2    4.0

Preparation Example 2 Preparation of Internal Solution and Comparative Solution Containing Vitamin B ₁ and B ₂

0.4 g of vitamin B ₁ (nitrate) and 0.4 g of vitamin B ₂ (phosphate ester) were dissolved in 40 L of purified water and 0.8 g in total, 2 g in total, 1 g in total, 2 g in total, 2 g in total, and 10 g in total, respectively.

Next, 8 L of each of the obtained solutions or deaerated purified water was taken into a pressure resistant container, and carbon dioxide was adjusted to pressurize the gas to be 3.2 kg / cm 3. This liquid was filled in the washed brown glass bottle, and what was capped was made into the oral solution.

Test Example 2

In the same manner as in Test Example 1, five normal subjects evaluated the degree of unpleasant taste and the degree of unpleasant smell of the oral solution prepared in Production Example 2.

Table 3 shows the evaluation of the taste of the oral solution containing vitamins B ₁ and B ₂ , and Table 4 shows the evaluation of the smell.

[Table 3]

Vitamin B ₁ + Vitamin B ₂ (µg / mL)    0 + 0   10 + 10   25 + 25   50 + 50  250 + 250
CO ₂ (kg / cm 3)      0    5.0    2.0    1.4    1.2    1.0     3.2    5.0    4.8    4.6    4.4    4.2

[Table 4]

Vitamin B ₁ + Vitamin B ₂ (µg / mL)    0 + 0   10 + 10   25 + 25   50 + 50  250 + 250
CO ₂ (kg / cm 3)      0    5.0    1.8    1.6    1.4    1.2     3.2    5.0    4.6    4.6    4.4    4.4

Preparation Example 3 Preparation of Internal Solution and Comparative Solution Containing Vitamin B ₁ and B ₆

In total, 0.4 g of vitamin B ₁ (nitrate) and 0.4 g of vitamin B ₆ (hydrochloride) were dissolved in 40 L of purified water, respectively, in total of 0.8 g, 1 g in total, 2 g in total, 2 g in total, 4 g in total, and 10 g in total.

Next, either 8 L of each of the obtained solutions or deaerated purified water was taken into a pressure-resistant container, and carbon dioxide was adjusted to pressurize the gas to be 3.2 kg / cm 3. This liquid was filled in the washed brown glass bottle, and what was capped was made into the oral solution.

Test Example 3

In the same manner as in Test Example 1, five normal subjects evaluated the degree of unpleasant taste and the degree of unpleasant smell of the oral solution prepared in Production Example 3.

Table 5 shows evaluation of the taste of the oral solution containing vitamins B ₁ and B ₆ and Table 6 shows the evaluation of the smell.

TABLE 5

Vitamin B ₁ + Vitamin B ₆ (µg / mL)    0 + 0   10 + 10   25 + 25   50 + 50  250 + 250
CO ₂ (kg / cm 3)      0    5.0    2.4    1.8    1.4    1.0     3.2    5.0    4.8    4.8    4.6    4.6

TABLE 6

Vitamin B ₁ + Vitamin B ₆ (µg / mL)    0 + 0   10 + 10   25 + 25   50 + 50  250 + 250
CO ₂ (kg / cm 3)      0    5.0    2.2    1.8    1.6    1.2     3.2    5.0    4.6    4.6    4.4    4.2

Preparation Example 4 Preparation of Internal Solution and Comparative Solution Containing Vitamin B ₁ , B ₂ and B ₆

Dissolve 1.2 g of vitamin B ₁ (nitrate), vitamin B ₂ (phosphate ester), and vitamin B ₆ (hydrochloride) in total of 1.2 g, 1 g in total of 3 g, 2 g in total of 6 g, and 10 g in total of 30 g in 40 L of purified water, Degassing treatment was performed.

Next, either 8 L of each of the obtained solutions or deaerated purified water was taken into a pressure-resistant container, and carbon dioxide was adjusted to pressurize to a gas internal pressure of 3.2 kg / cm 3. This solution was filled in the washed brown glass bottle, and what was capped was used as an internal oral solution.

Table 7 shows the evaluation of the taste of the oral solution containing vitamins B ₁ , B ₂ and B ₆ , and Table 8 shows the evaluation of the smell.

TABLE 7

Vitamin B ₁ + B ₂ + B ₆ (µg / mL)    0 + 0 + 0   10 + 10 + 10  25 + 25 + 25   50 + 50 + 50  250 + 250 + 250
CO ₂ (kg / cm 3)     0    5.0    1.8    1.2    1.0    1.0    3.2    5.0    4.8    4.6    4.4    4.2

[Table 8]

Vitamin B ₁ + B ₂ + B ₆ (µg / mL)    0 + 0 + 0   10 + 10 + 10   25 + 25 + 25   50 + 50 + 50  250 + 250 + 250
CO ₂ (kg / cm 3)     0    5.0    2.0    1.4    1.2    1.0    3.2    5.0    4.8    4.8    4.2    4.0

Claims (2)

An oral solution containing unpleasant taste and odor derived from vitamin B ₁ containing ₁ μg / mL or more of vitamin B ₁ and 1.0 to 4.0 kg / cm 3 of carbon dioxide at a gas internal pressure. A method of reducing unpleasant taste and odor derived from vitamin B ₁ of a vitamin B ₁ oral solution which contains 1.0 to 4.0 kg / cm 3 of carbon dioxide in an internal oral solution containing ₁ μg / mL or more of vitamin B ₁ .