KR20080079644A - Liquid medicine for internal use - Google Patents

Abstract

A liquid medicine for internal use characterized by containing glucuronolactone and dichloroacetic acid/diisopropylamine. The liquid medicine for internal use has a pH of preferably 1.5 to 3.0. The proportion of the glucuronolactone to the dichloroacetic acid/diisopropylamine is preferably from 3:1 to 340:1.

Description

Liquid preparation for oral medicine {LIQUID MEDICINE FOR INTERNAL USE}

The present invention relates to an oral solution containing glucuronolactone and dichloroacetic acid diisopropylamine, and more particularly to a composition having an effect of improving liver function and a fatigue recovery effect.

This application claims priority based on Japanese Patent Application No. 2005-376804 for which it applied on December 28, 2005, and uses the content here.

Background Art Conventionally, glucuronolactone has been used for treatment of improvement of liver function, urticaria, eczema, addiction, pregnancy morning sickness, pregnancy addiction, and the like. Moreover, it is a useful drug which is known as an effect as a preventive agent of alcoholic fatty liver resulting from large intake of alcohol or fat.

In such an oral solution containing glucuronolactone, it is required to further improve the liver function improving action, and as a measure therefor, an increase in glucuronolactone and a combination with other active ingredients. This is considered.

It is known that glucuronolactone is stable on the acidic side, and about the ingredient which can coexist stably with glucuronolactone to further improve the liver function improving action, Patent Document 1 describes a herb called licorice and wolfberry. It is described.

Patent Document 1: Japanese Patent Application Laid-Open No. 10-298093

However, increasing the glucuronolactone is difficult because the astringent taste of the glucuronolactone raw material itself is strong.

On the other hand, when the herbal medicine as described in the said patent document 1 is mix | blended as another active ingredient, the flavor of a liquid agent will be impaired.

This invention is made | formed in view of the said situation, and in the internal preparation liquid containing glucuronolactone WHEREIN: While ensuring the stability of glucurono lactone, it went to a specific compounding ratio, without impairing the flavor of a liquid formulation. It aims at further improving a function improvement effect and a fatigue recovery effect.

(Means to solve the task)

MEANS TO SOLVE THE PROBLEM The present inventors earnestly research in order to find the component which does not impair the flavor of a liquid agent, and can coexist stably with glucuronolactone which is stable on an acidic side, and can further improve liver function improvement effect. It was. As a result, it was found that by adding dichloroacetic acid diisopropylamine, while ensuring the stability of glucuronolactone, without improving the flavor of the liquid agent, it is possible to improve the function of the liver and the effect of fatigue recovery. Invented.

In other words, the present invention provides a glucononolactone and dichloroacetic acid diisopropylamine containing an internal liquid solution.

It is preferable that the formulation pH of the said internal use liquid preparation is 1.5-3.0.

Moreover, it is preferable that the compounding ratio (mass ratio) of glucuronolactone and dichloroacetic acid diisopropylamine is 3: 1 to 340: 1 (glucuronolactone / dichloroacetic acid diisopropylamine = 3 to 340).

In the present invention, the formulation pH means the pH of an oral liquid preparation that is stored as a final product and is provided for ingestion.

(Effects of the Invention)

According to the present invention, the stability of glucuronolactone can be ensured, and the internal preparation liquid which further improved liver function improvement effect and fatigue recovery effect can be obtained, without impairing the flavor of liquid solution.

The internal liquid solution of this invention contains (A) glucuronolactone and (B) dichloro acetic acid diisopropylamine.

<(A) glucuronolactone>

In the present specification, the term "glucuronolactone" is used as a generic term for glucuronolactone and glucuronic acid or salts thereof.

(A) Glucuronolactone is a component which improves the action of the liver, specifically, it has the effect of increasing the blood flow of the liver and improving the detoxification ability, and there are almost no side effects. It can also be applied to droughts, eczema and pregnancy addiction.

(A) The properties of glucuronolactone are white or pale yellow white crystals or crystalline powder.

(A) A glucuronolactone may be a commercial item, or a compound synthesize | combined suitably. The method for synthesizing (A) glucuronolactone is not particularly limited and can be appropriately selected according to the purpose.

There is no restriction | limiting in particular in content of (A) glucuronolactone in the internal preparation liquid of this invention, It can select suitably according to the objective. As a mass% unit, 0.01-10.0 mass% is preferable, for example, and 0.1-5.0 mass% is more preferable. As mg / ml unit, 10 mg / 100 ml-2,000 mg / 20 ml are preferable, for example, 100 mg / 100 ml-1,000 mg / 20 ml are more preferable.

If it is more than the lower limit of the said content, the favorable effect by glucuronolactone can be acquired. By using below the upper limit of the said content, unpleasant taste peculiar to glucuronolactone is suppressed from being remarkable, and the flavor of a liquid agent is not impaired.

<(B) dichloroacetic acid diisopropylamine>

(B) Dichloroacetic acid diisopropylamine is a component which improves the action of the liver, and specifically promotes the neoplasia of the liver cells.

The property of (B) dichloroacetic acid diisopropylamine is a white crystalline powder.

(B) Dichloroacetic acid diisopropylamine may be a commercial item, and may be a compound synthesize | combined suitably. There is no restriction | limiting in particular in the method of synthesize | combining (B) dichloroacetic acid diisopropylamine, According to the objective, it can select suitably.

There is no restriction | limiting in particular in content of (B) dichloroacetic acid diisopropylamine in the internal use liquid agent of this invention, It can select suitably according to the objective. As mass% unit, 0.003-0.5 mass% is preferable, for example, 0.003-0.15 mass% is more preferable. As mg / ml unit, 3 mg / 100 ml-100 mg / 20 ml is preferable, for example, 3 mg / 100 ml-30 mg / 20 ml are more preferable.

If it is more than the lower limit of the said content, the favorable effect by dichloroacetic acid diisopropylamine can be acquired. By carrying out below the upper limit of the said content, the burden to a liver can be reduced and the neogenesis of the liver cell can be promoted more efficiently.

In the internal-use liquid preparation of the present invention, the blending ratio of (A) glucuronolactone and (B) dichloroacetic acid diisopropylamine is not particularly limited, and depending on the purpose within the preferable ranges of the respective contents described above. It can use combining them suitably.

<Preferred blending ratio of glucuronolactone and dichloroacetic acid diisopropylamine>

As a preferable compounding ratio (glucuronolactone (A): dichloroacetic acid diisopropylamine (B)) in the internal liquid solution of said (A) glucuronolactone and (B) dichloroacetic acid diisopropylamine, it is mass. It is preferable that it is 3: 1 to 340: 1 in a unit of%, and it is more preferable that it is 30: 1 to 340: 1. In this range, the fatigue recovery effect is particularly excellent.

<pH preparations>

As for the formulation pH (25 degreeC) of the internal use liquid preparation of this invention, 1.5-3.0 are preferable, and a pH preparation agent is added as needed.

The more preferable range of the said formulation pH is 2.0-3.0, and especially preferable range is 2.2-2.8.

If formulation pH is more than the lower limit of the said range, sourness is not too strong and the flavor of a liquid agent is not impaired. By making formulation pH below the upper limit of the said range, the favorable stability of (A) glucuronolactone can be obtained. In addition, at formulation pH in the above range, the stability of (B) dichloroacetic acid diisopropylamine is good.

There is no restriction | limiting in particular as a pH adjuster, According to the objective, it can select suitably, For example, hydrochloric acid, dilute hydrochloric acid, citric acid, sodium citrate, glycine, gurucono- delta-lactone, succinic acid, acetic acid, tartaric acid, D-tartrate, Examples of pH regulators such as sodium hydroxide, potassium hydroxide, magnesium hydroxide, lactic acid, calcium lactate, glacial acetic acid, fumaric acid-sodium, maleic acid, citric anhydride, DL-apple acid, aspartic acid, glutamic acid, adipic acid, gluconic acid, fumaric acid and sodium bicarbonate Can be. Said pH adjuster can be used individually by 1 type or in combination of 2 or more type.

<Other ingredients>

The internal liquid solution of this invention can contain arbitrary components in the range which does not impair the effect of this invention other than the component mentioned above.

Specific examples of the optional ingredients include vitamins, sweeteners, preservatives (preservatives), stabilizers, preservatives, solubilizers, solvents, dissolution aids, suspending agents, antioxidants, flavoring agents, flavoring agents, fresheners, colorants, buffers, herbal medicines, caffeine And royal jelly. In addition, the addition amount of these arbitrary components can be mix | blended normally in the range which does not prevent the effect of this invention.

There is no restriction | limiting in particular as said vitamins, According to the objective, it can select suitably, For example, vitamin B1, such as vitamin B, such as vitamin A and nitrate nitrate, vitamin B2, such as riboflavin sodium phosphate, vitamin B6, such as nicotinic acid amide, pyridoxine hydrochloride, Vitamin C, such as vitamin B12, vitamin D, vitamin E, vitamin C, such as ascorbic acid, and calcium pantothenate, are mentioned. Said vitamins can be used individually by 1 type or in combination of 2 or more types.

There is no restriction | limiting in particular as said sweetener, According to the objective, it can select suitably, For example, cane sugar, liquid sugar, fructose, fructose glucose liquid, glucose fructose liquid sugar, brown sugar, high fructose liquid sugar, glucose, lactose, White sugar, refined white sugar, refined white sugar, granulated sugar, honey, refined honey, sugar syrup, erythritol, xylitol, D-sorbitol, D-sorbitol liquid, maltitol, maltitol liquid Sugar alcohols such as, maltose, D-mannitol, aspartame, acesulfame potassium, persimmon extract, licorice extract, saccharin, saccharin sodium, sucralose, stevia extract, neo-teme, taumatin, glycine, glycerin, glycyrrhizin Sweeteners such as dipotassium, disodium glycyrrhinate, trisodium glycyrrhinate, monoammonium glycyrinate and licorice. Said sweetener can be used individually by 1 type or in combination of 2 or more type.

There is no restriction | limiting in particular as said preservative (preservative), According to the objective, it can select suitably, For example, benzoic acid, sodium benzoate, ethanol, sodium edetic acid, dry sodium sulfite, agar, dl-camper, citric acid, Sodium citrate, glycerin, salicylic acid, sodium salicylate, phenyl salicylate, D-sorbitol, sorbic acid, potassium sorbate, sodium dihydroacetic acid, white sugar, honey, paraoxybenzoic acid isopropyl, paraoxybenzoic acid isopropyl, para Preservatives, such as ethyl oxybenzoate, butyl paraoxybenzoate, propyl paraoxybenzoic acid, methyl paraoxybenzoate, propylene glycol, 1-menthol, and eucalyptus oil, are mentioned. Said preservative can be used individually by 1 type or in combination of 2 or more type.

There is no restriction | limiting in particular as said stabilizer, According to the objective, it can select suitably, For example, adipic acid, ascorbic acid, L-ascorbic acid stearic acid ester, L-ascorbic acid sodium, L-aspartic acid, L- Sodium aspartic acid, aminoethylsulfonic acid, DL-alanine, sodium hydrogen sulfite, sodium sulfite, L-arginine, sodium alginate, propylene glycol alginate, albumin, benzoic acid, ethanol, sodium edetate, sodium edetate, calcium chloride, sodium chloride, Magnesium chloride, cacao fat, fructose, carboxyvinyl polymer, calcium carmellose, sodium carmelose, dry sodium carbonate, xanthan gum, xylitol, glycine, glycerin, glycerin fatty acid ester, sodium glycyrrhinate, glucono-δ-lactone, Calcium gluconate, crystalline cellulose, sodium acetate, sodium salicylate, phenyl salicylate, β-cyclodex Lean, dibutylhydroxytoluene, tartaric acid, sucrose fatty acid ester, calcium hydroxide, sodium hydroxide, magnesium hydroxide, refined gelatin, refined soy lecithin, refined white sugar, sesquiorenate sorbitan, cetanol, gelatin, sorbitan fatty acid ester, D-sorbitol, D-sorbitol solution, soybean oil non-compound, dextran, natural vitamin E, tocopherol, d-δ-tocopherol nicotinic acid amide, lactose, concentrated glycerin, white sugar, microcrystalline cellulose, hydroxypropylcellulose, glacial acetic acid, sodium pyrosulfite , Butylhydroxyanisole, glucose, fumaric acid, fumaric acid-sodium, propylene glycol, bentonite, boric acid, molybdenum propyl, povidone, polyacrylic acid partial neutralization, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol, polysorb Beet, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl alcohol dibutyl ether horn Water, macrogol, maltose, maleic acid, malonic acid, D-mannitol, citric acid anhydride, sodium citrate anhydrous, sodium pyrophosphate anhydrous, maleic anhydride, sodium metaphosphate, methylcellulose, l-menthol, aluminum monostearate, glycerin monostearate And stabilizers such as sodium lauryl sulfate, egg white albumin and DL-peracid. Said stabilizer can be used individually by 1 type or in combination of 2 or more type.

There is no restriction | limiting in particular in the method of preparing the internal preparation liquid of this invention, A well-known method can be used suitably. For example, it can be manufactured in accordance with the provisions of the General Regulations of the Japan Pharmacy Law, "Liquid formulation", filtered and sterilized.

The oral solution of the present invention is ingested orally as a liquid oral preparation. There is no restriction | limiting in particular in particular, According to the objective, it can select suitably, but when it is an adult, the intake amount of (A) glucuronolactone per dose is 30-10000 mg (0.03-10 g), and (B) dichloro It is preferable to ingest once a day in the intake amount of diisopropylamine acetate per 3 to 500 mg (0.003-0.5 g).

The internal liquid solution of the present invention is a component that improves the action of the liver, and in addition to (A) glucuronolactone having high stability in the acidic region, a component that improves the action of the liver, and high stability under acidic conditions. Since it contains diisopropylamine acetate, the stability of an active ingredient is high, and the outstanding liver function improvement effect and fatigue recovery effect can be acquired. Moreover, the flavor does not deteriorate remarkably by addition of (B) dichloroacetic acid diisopropylamine, and even if it adds (B) dichloroacetic acid diisopropylamine in the above-mentioned preferable addition amount range, a flavor is not impaired.

Especially in the range of formulation pH1.5-3.0, the good stability of the active ingredient and the effect of improving the liver function are obtained, and the compounding ratio of glucuronolactone and dichloroacetic acid diisopropylamine is 3: 1 to 340: 1. A higher effect can be obtained.

(Example)

Although an Example demonstrates this invention further in detail below, this invention is not limited to these Examples.

(Examples 1 to 10 and Comparative Examples 1 and 2)

<Preparation of internal preparation liquid>

100 ml of internal preparation liquid was prepared by the routine method so that it might become the composition and preparation pH shown in the following table.

About the obtained oral solution, the stability and liver function improvement effect (as a fatigue recovery effect, 7-step sensory evaluation) and the fatigue recovery effect (flicker value) were evaluated with the following method. The evaluation results are shown in the table below.

<Evaluation of stability>

A brown glass bottle was filled with an internal liquid solution, stored at 60 ° C. for 3 weeks, and the content of glucuronolactone before and after storage was measured, respectively. The ratio (mass basis) of content after storage with respect to the value (initial value) of content before storage (right after preparation) was calculated | required, and stability was evaluated based on the following evaluation criteria. In addition, it is judged that the effect of this invention was confirmed by evaluation of "(circle)" or more.

[Evaluation standard]

(Double-circle): Very stable (resistance rate is 95% or more and 100% or less with respect to an initial value).

(Circle): Stable (per initial value, residual rate is 90% or more and less than 95%).

X: Unstable (residual ratio is less than 90% with respect to initial value).

<Evaluation of liver function improving action (as fatigue recovery effect)>

First, the liver function improving effect (fatigue recovery effect) was evaluated by the following method.

A brown glass bottle was filled with a liquid for internal use, and 10 panelists were drinking this, and the degree of fatigue recovery of the next day was sensory evaluation based on the following evaluation criteria, and the average value of 10 people was calculated | required. Moreover, it is judged that the effect of this invention was confirmed on the average value 5.0 points or more.

[Evaluation standard]

7: The effect of fatigue recovery was very felt.

6: felt the effect of fatigue recovery quite.

5: I felt the effect of fatigue recovery slightly.

4: I can't say either.

3: I did not feel the effect of fatigue recovery.

2: little effect of fatigue recovery.

1: The effect of fatigue recovery was not felt at all.

<Evaluation of the fatigue recovery effect (flicker value)>

The liver function improvement effect (fatigue recovery effect) was evaluated by the following method using the scintillation measuring apparatus (The Daikei Instruments Industry Co., Ltd. make, brand name: Digital Flicker T.K.K.502).

(1) Measure initial flicker value (average of 5 repetitions).

(2) Drinking a brown glass bottle filled with an oral solution.

(3) Measure flicker value 5 hours after drinking (average of 5 repetitions).

(5 hours from drinking to measuring.)

(4) Calculate the rate of change for the initial value.

It is determined that the effect of the present invention is confirmed when the rate of change of the flicker value is 85% or more. The flicker value indicates the boundary at which flashing light is recognized as continuous light instead of intermittent light in terms of the frequency of light (Hz). The larger this value, the smaller the visual fatigue can be considered. Typical normal value was 35 Hz and initial value in this measurement was about 35 Hz.

TABLE 1

TABLE 2

TABLE 3

TABLE 4

As shown in the said Tables 1-4, the Examples 1-17 which concerns on this invention were all favorable in stability, and the liver function improvement effect was also favorable. In addition, the liquid solution of either embodiment was satisfactory without a problem in flavor and could be drunk without resistance.

In particular, in Comparative Example 2 containing glucuronolactone and not containing dichloroacetic acid diisopropylamine, the evaluation of liver function improving action was 4.8. In Example 7, in which the content and the pH value were the same, and 30 mg / 100 ml of dichloroacetic acid diisopropylamine was added, the evaluation of the hepatic function improving effect was improved to 6.2, and the stability was superior to that of Comparative Example 2. .

Moreover, in Comparative Examples 1 and 3 containing no glucuronolactone and containing dichloroacetic acid diisopropylamine, evaluations of liver function improving action were low at 4.2 and 4.6. In Comparative Examples 1 and 3, since glucuronolactone was not blended, stability was not evaluated.

(Examples 18 to 22)

<Preparation of internal preparation liquid>

As a prescription example of an oral solution, 100 ml of an oral solution was prepared by a routine method so as to have a composition and formulation pH shown in Table 4 below.

In addition, all of Examples 18 to 22 according to the present invention had good stability, and also had a hepatic function improving effect and a fatigue recovery effect.

TABLE 5

The internal use liquid preparation of this invention can be used in the field | areas, such as a medical industry, For example, it can be used suitably as a medicine, an quasi drug, a drink, etc.

Claims (3)

An internal liquid solution containing glucuronolactone and dichloroacetic acid diisopropylamine. The method of claim 1, Formulation solution pH is 1.5-3.0, The oral solution characterized by the above-mentioned. The method according to claim 1 or 2, The compounding solution for glucuronolactone and dichloroacetic acid diisopropylamine is 3: 1 to 340: 1.