KR20030042547A - Levosulpiride liquid formulation composition and method of preparing the same - Google Patents

Abstract

PURPOSE: Provided are a levosulpiride liquid formulation composition which comprises levosulpiride as an active ingredient and at least one kind of pharmaceutically acceptable acids and a method of preparing the same. CONSTITUTION: A levosulpiride liquid formulation composition is characterized by comprising 0.001-30 wt.% of levosulpiride as an active ingredient based on the total weigh of the liquid formulation composition and 0.001-30 wt.% of at least one kind of pharmaceutically acceptable acids. It further comprises cyclodextrin for masking a bitter taste peculiar to levosulpiride.

Description

Levosulpiride liquid formulation composition and method of preparing the same

The present invention relates to a levosulfide liquid formulation and a method for producing the same.

Levosulfide is used as a gastrointestinal motility enhancer used for symptoms such as bloating, epigastric discomfort, heartburn, belching, nausea and vomiting due to functional dyspepsia.

Levosulfide formulations are poorly soluble in water, have a distinctive bitter taste, and have not been developed as a liquid because of other formulation difficulties, and are currently developed and marketed as tablets only. This tablet contains 25 mg of levosulfide per tablet, with a single dose of 25 mg per adult. However, there is a problem in that the bioavailability of levosulfide is low because the drug is easy to take, but is difficult to take in the gastrointestinal tract, and thus the expression of the drug is slow. The demand for this is increasing.

Examples of the agent used as an agent for improving gastrointestinal motility function include domperidone preparations, metoclopramide preparations, cisapride preparations, and levosulfide preparations, which are the subject of the present invention. Domperidone formulations are commercially available in tablets, solutions, syrups and suspensions, metoclopramide is available in tablets, and cisapride formulations are available in tablets, solutions, and suspensions. Among them, in the case of domperidone preparations, a solubilization method and a method of preparing a liquid formulation with a solubilized domperidone solution have already been disclosed in several patents and documents (Korean Food and Drug Administration Notification No. 1998-127, Publication No. 95-10149, application). No. 1995-146413 and Publication No. 98-8229). Although these patents and documents suggest conditions for the preparation of liquid and suspension formulations of domperidone formulations, the biggest drawback in common is that it is necessary to go through several stages of manufacturing during mass production. In order to produce, the manufacturing process requires excessive time.

Accordingly, the present invention provides a pharmaceutical composition and a method for preparing the same, wherein the drug expression of poorly soluble levosulfide in water is quick and easy to take, and the manufacturing process is simple, thereby reducing time and cost. The purpose.

The present invention relates to a levosulfide liquid formulation and a method for producing the same.

Specifically, the present invention relates to a levosulfide liquid formulation composition and a method for producing the same, comprising levosulfide as an active ingredient and at least one component of a pharmaceutically acceptable acid.

The first aspect of the present invention relates to a levosulfide liquid formulation composition comprising levosulfide as an active ingredient and at least one component of a pharmaceutically acceptable acid.

At this time, it is preferable that the levosulfide liquid formulation of the present invention contains 0.001 to 30% by weight of levosulfide based on the total weight of the composition.

When the revosulphilide content is less than 0.001% by weight, there is a problem in that the dose is increased when one adult is used, and when it exceeds 30% by weight, it is difficult to mask the bitter taste.

The following scheme depicts the reaction mechanism in the acidic solution of levosulfide.

Here, HX is a pharmaceutically acceptable acid and levosulfide forms an ammonium salt with acid to form a reaction mechanism that dissolves in water.

As the acid that can be used in the levosulfide liquid formulation of the present invention, one or more pharmaceutically acceptable acids can be used. Preferably, citric acid, tartaric acid, hydrochloric acid, glutamic acid, glacial acetic acid, benzoic acid, malic acid, sulfuric acid, tannic acid, One or more components selected from the group consisting of adipic acid and lactic acid can be used.

In this case, it is preferable that the levosulfide liquid formulation of the present invention contains an acid in an amount of 0.001 to 30% by weight based on the total weight of the composition.

When the acid content is less than 0.001% by weight, there is a problem that the solubility of the levosulfide is low when heating the preparation of the levosulfide liquid formulation, and when it exceeds 30% by weight, the acid has a strong side effect that damages the gastrointestinal tract when taken. Because it occurs.

In addition, the levosulfide liquid formulation of the present invention may further include cyclodextrins. Cyclodextrins can mask the bitterness peculiar to levosulfide by forming a clathrate compound in a solubilized levosulfide solution.

As for the molar ratio with respect to levosulfide, the usage-amount of cyclodextrins is 1: 0.1-10, More preferably, it is 1: 1-3, Especially preferably, it is 1: 2.

Cyclodextrins that can be used in the liquid composition of the present invention include pharmaceutically acceptable cyclodextrins such as beta-cyclodextrin, hydroxypropyl beta-cyclodextrin, gamma-cyclodextrin, and alpha-cyclodextrin, and derivatives thereof. Preference is given to using at least one component selected from the group consisting of.

The levosulfide liquid formulation of the present invention may further comprise conventional adjuvants such as pharmaceutically acceptable sweeteners, preservatives, solvents, dissolution aids, fragrances, viscosity regulators, pH regulators and the like. In addition, if necessary, it may further include a pharmaceutically acceptable colorant for color control of the levosulfide liquid formulation.

Sweeteners that can be used in the liquid formulation of the present invention include pharmaceutically acceptable natural sweeteners and synthetic sweeteners. Natural sweeteners include white sugar, compressed sugar, confectionary sugar, glucose, starch syrup, fructose, isomerized sugar, maltose, honey, lactose, xylose, fructooligosaccharide and the like; Sugar alcohols include sorbitol, di-sorbitol, maltitol, mannitol and the like; Glycosides, salts thereof, steviosides, and the like as glycosides; Examples of proteins include doomatine. As a synthetic sweetener, Aspartame; Saccharin derivatives including saccharin, saccharin calcium and sodium saccharin; Altam; Aksulfame-K; L-sugar; glycerin; Cyclodextrins and derivatives thereof such as beta-cyclodextrin, hydroxypropyl beta-cyclodextrin, gamma-cyclodextrin, alpha-cyclodextrin, and the like; Dextrose, lacturose, reducing palatinose, isomaltoligosaccharide, etc. are mentioned. The materials can be used as a single component or as a mixture of two or more.

Preservatives that can be used in the liquid formulation of the present invention include pharmaceutically acceptable preservatives, for example, benzoic acid, sodium benzoate, potassium benzoate, calcium benzoate, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, Isopropyl paraoxybenzoate, butyl paraoxybenzoate, isobutyl paraoxybenzoate, sorbic acid, potassium sorbate, sodium sorbate, dihydroacetic acid, sodium dihydroacetate, chlorobutanol, benzalkonium chloride, benzaltonium chloride, phenol ( p ) , Cresol, chlorocresol, benzyl alcohol and other non-toxic preservatives. The materials can be used as a single component or as a mixture of two or more.

As a solvent which can be used for the liquid composition of this invention, purified water (pharmacopoeia), physiological saline, ethanol, the mixture of ethanol and purified water, isopropyl alcohol, etc. are mentioned.

As a dissolution aid in the present invention, ethanol (pharmaceutical); Propylene glycol; Polyethylene glycols such as polyethylene glycol 200 to 8000; Polyoxyethylene monoalkyl ethers; Polyoxyethylene castor oil derivatives; Polyoxyethylene sorbitol fatty acid esters including polysorbate and twin esters; Monostearic acid sucrose; Lanolin esters; Lanolin ethers; Poloxamer (Pluronic); Sodium citrate; Dilute hydrochloric acid; Pharmaceutically acceptable dissolution aids, including dilute sulfuric acid and the like, can be used as a single component or as a mixture of two or more thereof.

As a fragrance that can be used in the liquid composition of the present invention, peppermint oil, methyl salicylate, nutmeg oil, orange flower oil, orange flower water, orange oil, sweet orange peel tink, complex orange spirit, peppermint, peppermint oil, peppermint alcohol, Fine needle oil, rose oil, farm oil, spearmint, spearmint oil, chimol, toluvalsamtink, vanillin, vanilla, vanilla tink, fennel oil, licorice, pure licorice extract, liquid glucose, benzaldehyde, anetol, caraway oil, Caraway, Cardamom Oil, Almond Oil, Cardamom Seeds, Cardamom Tink, Complex Cardamom, Cherry Juice, Cinnamon and Cinnamon Oil, Clover Oil, Cocoa, Coriander Oil, Eriodction Fluid Extract, Eriodction, Ethyl Acetate, Ethyl vanillin, eucalyptus, lavender oil, lemon oil, menthol, ginger and various fruit and other non-toxic fragrances can be used as a single ingredient or as a mixture of two or more. .

Viscosity modifiers that can be used in the liquid composition of the present invention, pharmaceutically acceptable raw material for viscosity adjustment, including xanthan gum, acacia gum, tragacanta powder, polyvinylpyrrolidone, ethyl cellulose, sodium carboxymethyl cellulose Can be used as a single component or as a mixture of two or more.

The pH adjusting agent that can be used in the liquid composition of the present invention may include sodium hydroxide, potassium hydroxide, prolamine, ammonia water, ammonium carbonate, etc. as the alkalizing agent, and non-toxic such as various phosphates including acetic acid and hydrochloric acid as acidifying agents. pH adjusters can be used.

At this time, the pH is preferably 7 or less acidic region, more preferably pH 0.1 ~ 6.0, even more preferably pH 1.0 ~ 5.0 range.

As a coloring agent which can be used for the liquid composition of this invention, it is a red color | collar No. 3, red 40, yellow 4, yellow 5, yellow 203, green 3, blue 1, blue 2, etc. as a tar color for internal use. Various pharmaceutically acceptable pigments and other non-toxic pigments may be used as a single component or as a mixture of two or more thereof.

The levosulfide liquid composition of the present invention can be formulated into liquid, syrup, gel, and disposable drink formulations that are easy to take and take effect quickly and are easy to store for a long time.

The second aspect of the present invention provides a method for preparing a levosulfide liquid composition by dissolving at least one pharmaceutically acceptable acid component in purified water and then dissolving levosulfide, and adding additional components as necessary. It is to provide a method for producing a levosulfide liquid, characterized in that.

Hereinafter, the contents of the present invention will be described in detail with reference to Examples, Formulation Examples and Experimental Examples, but the present invention is not limited thereto.

Example.

While varying the type of acid used in the levosulfide liquid formulation of the present invention, the levosulfide liquid formulations for the respective compositions of Table 1 were prepared.

Composition 1 Composition 2 Composition 3 Composition 4 Composition 5 Composition 6 Composition 7 Composition 8 Composition 9 Composition 10 Composition 11 Composition 12 Levosulfide (unit: g) 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 Betacyclodextrin (g) 1.7 1.7 1.7 - - - - - - - - - Hydroxypropyl beta-cyclodextrin (g) - - - 2.02 2.02 2.02 - - - - - - Gamma-cyclodextrin (g) - - - - - - 1.9 1.9 1.9 - - - Alpha-cyclodextrin (g) - - - - - - - - - 1.42 1.42 1.42 Stevioside (g) 1.0 - - 1.0 - - 1.0 - - 1.0 - - Aspartame (g) - 1.0 - - 1.0 - - 1.0 - - 1.0 - Saccharin Sodium (g) - - 1.0 - - 1.0 - - 1.0 - - 1.0 Sodium benzoate (g) 0.95 0.95 0.95 0.95 0.95 0.95 0.95 0.95 0.95 0.95 0.95 0.95 Di-sorbitol solution (g) 200 200 200 200 200 200 200 200 200 200 200 200 Strawberry Essence (ml) One One One One One One One One One One One One

Example 1-1.

About the composition 1 of the said Table 1, it carried out according to the following method and manufactured the liquid composition.

1.0 g of citric acid was added and dissolved in 300 ml of purified water, and 250 mg of levosulpyrid was completely dissolved by stirring. Then, about 1.7 g of beta-cyclodextrin was added to dissolve completely (1).

Separately, 200 g of di-sorbitol solution was added to 150 ml of purified water, mixed by stirring, and 1.0 g of stevioside was added to completely dissolve it (2).

Separately, 0.95 g of sodium benzoate was added to 200 ml of purified water, followed by stirring to dissolve it (3).

The solution of (1) was added to the solution of (1), followed by stirring and mixing. Then, the solution of (3) was added thereto, then 1 ml of strawberry essence was added. 1000 ml (by virtue) was filled and packaged, to prepare a levosulfide liquid composition.

Examples 1-2 to 1-12.

As the acids, 1.0 g of citric acid was used, and other compositions were prepared as described in Table 1 (compositions 2 to 12), and respective levosulfide liquid composition was prepared in the same manner as in Example 1-1.

Examples 2-1 to 2-12.

As the acids, 1.0 g of tartaric acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid composition was prepared in the same manner as in Example 1-1.

Examples 3-1 to 3-12.

1.0 g of hydrochloric acid was used as the acid, and the other compositions were prepared as described in Table 1 (composition 1 to 12), and the respective levosulfide liquid composition was prepared in the same manner as in Example 1-1.

Examples 4-1 to 4-12.

As the acids, 1.0 g of glutamic acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid composition was prepared in the same manner as in Example 1-1.

Examples 5-1 to 5-12.

1.0 g of glacial acetic acid was used as an acid, and other compositions were prepared as shown in Table 1 (composition 1-12), and each levosulfide liquid formulation composition was manufactured by the method similar to Example 1-1.

Examples 6-1 to 6-12.

As the acids, 1.0 g of benzoic acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid formulations were prepared in the same manner as in Example 1-1.

Examples 7-1 to 7-12.

As the acids, 1.0 g of malic acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid formulations were prepared in the same manner as in Example 1-1.

Examples 8-1 to 8-12.

As the acids, 1.0 g of sulfuric acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid composition was prepared in the same manner as in Example 1-1.

Examples 9-1 to 9-12.

As the acids, 1.0 g of tannic acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid composition was prepared in the same manner as in Example 1-1.

Examples 10-1 to 10-12.

As the acids, 1.0 g of adipic acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid formulations were prepared in the same manner as in Example 1-1.

Examples 11-1 to 11-12.

As the acids, 1.0 g of lactic acid was used, and other compositions were prepared as shown in Table 1 (compositions 1 to 12), and the respective levosulphilide liquid composition was prepared in the same manner as in Example 1-1.

Example 12-1.

About the composition 1 of the said Table 1, it carried out according to the following method and manufactured the liquid composition.

1.0 g of citric acid was dissolved in 300 ml purified water, and then 250 mg of levosulfide was completely dissolved by stirring. Then, about 1.7 g of beta-cyclodextrin was added to completely dissolve it (1).

Separately, 200 g of di-sorbitol solution was added to 150 ml of purified water, stirred and mixed, and 1.0 g of stevioside was added to dissolve completely (2).

Separately, 0.95 g of sodium benzoate was added to 200 ml of purified water, followed by stirring to dissolve it (3).

The solution of (1) was added to the solution of (1), stirred and mixed. Then, the solution of (3) was added thereto. Then, the pH was adjusted to 2.0-7.0 with 1 N sodium hydroxide solution. After filtration, 100 ml and 1000 ml (virtual) were packed and packed into glass bottles to prepare a levosulfide liquid composition.

Examples 12-2 to 12-12.

As the acids, 1.0 g of citric acid was used, and other compositions were prepared as described in Table 1 (compositions 2 to 12), and respective levosulfide liquid formulations were prepared in the same manner as in Example 12-1.

Examples 13-1 to 13-12.

As the acids, 1.0 g of tartaric acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid formulations were prepared in the same manner as in Example 12-1.

Examples 14-1 to 14-12.

As the acids, 1.0 g of hydrochloric acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid formulations were prepared in the same manner as in Example 12-1.

Examples 15-1 to 15-12.

As the acids, 1.0 g of glutamic acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid composition was prepared in the same manner as in Example 12-1.

Examples 16-1 to 16-12.

1.0 g of glacial acetic acid was used as an acid, and other compositions were prepared as shown in Table 1 (composition 1-12), and each levosulfide liquid formulation composition was manufactured by the method similar to Example 12-1.

Examples 17-1 to 17-12.

As the acids, 1.0 g of benzoic acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid formulations were prepared in the same manner as in Example 12-1.

Examples 18-1 to 18-12.

As the acids, 1.0 g of malic acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid formulations were prepared in the same manner as in Example 12-1.

Examples 19-1 to 19-12.

As the acids, 1.0 g of sulfuric acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid formulations were prepared in the same manner as in Example 12-1.

Examples 20-1 to 20-12.

As the acids, 1.0 g of tannic acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and respective levosulfide liquid composition was prepared in the same manner as in Example 12-1.

Examples 21-1 to 21-12.

As the acids, 1.0 g of adipic acid was used, and other compositions were prepared as described in Table 1 (compositions 1 to 12), and the respective levosulfide liquid composition was prepared in the same manner as in Example 12-1.

Examples 22-1 to 22-12.

As the acids, 1.0 g of lactic acid was used, and other compositions were prepared as shown in Table 1 (compositions 1 to 12), and the respective levosulfide liquid composition was prepared in the same manner as in Example 12-1.

Experimental Example 1. Solubility test of levosulfide

1) Solution used in the experiment: buffer solution to pH 1.2 ~ 13.0, purified water, 1% beta-cyclodextrin solution, 0.9% sodium chloride solution, 0.01 mol citric acid solution, 0.01 mol tartaric acid solution and 0.01 mol hydrochloric acid solution.

2) Preparation of calibration curve: Levosulfide was prepared to 50ppm, 100ppm, 200ppm and 1000ppm in each of the above solutions, followed by the content test method, and the results were plotted to prepare a calibration curve.

3) Solubility test

Preparation of Levosulfide Solution: A constant excess amount of levosulfide was added to each solvent, stirred for 15 hours, allowed to stand for 24 hours, filtered, diluted to an appropriate concentration, and tested according to the content test method for solubility.

Experimental Method: Stirring Speed: 150rpm, Stirring Temperature: 25 ℃

Three experiments were carried out for each solvent and the average value was recorded (Table 2).

In the solubility test of the buffer solution up to pH 1.2 ~ 13, as shown in Table 2, the experimental results confirmed that the practical solubility increases from alkaline to acidic. In particular, in the acidic region below pH 7.0, the solubility exceeded 700% compared to the alkaline, so that the solubility of levosulfide was excellent in the neutral region or less.

In addition, the solubility test in other acidic solutions also confirmed that the solubility of levosulfide was superior to the solubility in purified water.

Experimental Example 2 Stability Test with Time-dependent Change of Levosulfide Liquid Solution

Sample: 100 ml of the levosulfide solution prepared in Example 1-1 was used.

Test period: 2000. 1 ~ 2001. 2

Experiment method

Six months for each preservation method:

The content, pH, properties, identification test, and microbial test of levosulfide and sodium benzoate were performed per two months. Each experiment was performed three times for each sample number and the average value was recorded (Table 3).

The content test of levosulfide and sodium benzoate was carried out by high performance liquid chromatography.

As shown in Table 3, accelerated conditions (temperature: 40 ℃, humidity: 75%), long-term storage conditions (temperature: 25 ℃, humidity: 60%), harsh conditions (temperature: 60 ℃), and refrigerated conditions (temperature: 5 Results of the experiment at 3 ° C.) were performed three times per manufacturing number in the form of a property, pH, identification test, microbial test, preservative test, and content test, respectively. The results were almost the same as that of each test immediately after manufacture. In addition, in the direct sunlight and light shielding tests, which are tests for confirming the effect of light on a liquid when exposed to light, the results of the experiments immediately after the manufacture of the resin result in almost the same results, thus making the revosulpyridide liquid composition of the present invention very effective. It was found to be stable. In addition, as inferred from the results of 6 months of acceleration, it was confirmed that there is no problem even if the expiration date of the levosulfide solution developed by the researcher is 3 years.

Experimental Example 3 Confirmation of Decomposition Product Formation with Time-dependent Change of Levosulfide Liquid Solution

Sample: 100 ml of levosulfide liquid at the time of the final measurement was used according to the storage conditions carried out in Experimental Example 2.

Duration of laboratory: 2000. 1 ~ 2001.2

Type of experiment: Decomposition products were measured according to the content test method (Table 4).

Degradation product confirmation method: Three peaks (1.7 components, 2.6 components and 15.7 components) shown on the chromatogram were confirmed, and the presence or absence of the peaks appearing in addition to this was confirmed.

The experiment is a test to determine whether or not the revosulphilide, the main component of the levosulphilide solution injected under each storage condition, decomposes over time or generates other substances by decomposition or reaction of other injected materials. It was carried out simultaneously with the stability experiment of the sulfide liquid formulation.

As a result, it can be seen that no decomposition products were produced as shown in Table 4.

Formulation Example 1. Disposable Drink Formulations

The preparations from Examples 1 to 31 were filtered and then packed into 100 ml bottles and packed.

Formulation Example 2 Syrup Formulation

1.0 g of citric acid was added and dissolved in 300 ml of purified water, and 1250 mg of levosulfide was stirred to dissolve completely, and about 8.5 g of beta-cyclodextrin was added to dissolve completely (1).

Separately, 200 g of di-sorbitol solution was added to 150 ml of purified water, mixed by stirring, and 1.0 g of stevioside was added to completely dissolve it (2).

Separately, 0.95 g of sodium benzoate was added to 200 ml of purified water, followed by stirring to dissolve it (3).

To the solution of (1), the solution of (2) was added and stirred and mixed. Then, the solution of (3) was added. Then, 1 ml of strawberry essence was added, the volume was adjusted to 1000 ml with purified water, filtered and filled into a 20 ml bottle. It was prepared by packing.

Formulation Example 3 Gel Formulation

1.0 g of citric acid was added and dissolved in 300 ml of purified water, and 1250 mg of levosulfide was stirred to dissolve completely, and about 8.5 g of beta-cyclodextrin was added to dissolve completely (1).

Separately, 1 g of xanthan gum is completely dissolved in a homogenizer in 100 ml of purified water (2).

Separately, 200 g of di-sorbitol solution was added to 150 ml of purified water, stirred and mixed, and 1.0 g of stevioside was added to dissolve completely (3).

Separately, 0.95 g of sodium benzoate was added to 200 ml of purified water, followed by stirring to dissolve it (4).

The solution of (1) was added to the solution of (1) and stirred and mixed.The solution of (3) was added and stirred and mixed.The solution of (4) was added and mixed.Then, 1 ml of strawberry essence was added and the volume was purified with purified water. After 1000 ml, it was prepared by filtration and filling into a 20 ml pouch and packaging.

The preparation method of the present invention, solubilizing and masking the revosulpyridide that is poorly soluble in water and has a distinctive bitter taste, thereby making it easy to take a convenient and rapid medicinal effect as well as long-term storage liquids, syrups, gels and 1 It can be formulated as a disposable drink agent type and also develops a poorly soluble levosulfide as a liquid. By eliminating the heating process in all processes, it is possible to drastically reduce the time consumption due to the multi-step manufacturing process, and to make a simple and inexpensive manufacturing process. Can provide.

Claims (12)

A levosulfide liquid formulation composition comprising levosulfide and at least one component of a pharmaceutically acceptable acid. The levosulfide liquid composition according to claim 1, wherein the levosulfide is contained in an amount of 0.001 to 30% by weight based on the total weight of the liquid composition. 2. The levostulf of claim 1, wherein the pharmaceutically acceptable acids are at least one component selected from the group consisting of citric acid, tartaric acid, hydrochloric acid, glutamic acid, glacial acetic acid, benzoic acid, malic acid, sulfuric acid, tannic acid, adipic acid and lactic acid. Lead liquid formulation. 4. The levosulfide liquid formulation according to claim 3, wherein the pharmaceutically acceptable acid is contained in an amount of 0.001 to 30 wt% based on the total weight of the liquid composition. The levosulfide liquid formulation according to claim 1, wherein the levosulfide liquid formulation further comprises cyclodextrins. The levosulfide liquid composition according to claim 5, wherein the cyclodextrins are contained in a molar ratio of 1: 0.1 to 10 with respect to levosulfide. The method of claim 5, wherein the cyclodextrins are at least one component selected from the group consisting of beta-cyclodextrin, hydroxypropyl beta-cyclodextrin, gamma-cyclodextrin, alpha-cyclodextrin, and derivatives thereof. Levosulfide liquid formulation. The method of claim 1, wherein the levosulfide liquid formulation further comprises at least one component selected from the group consisting of pharmaceutically acceptable sweeteners, preservatives, solvents, dissolution aids, fragrances, viscosity regulators, pH regulators and colorants. A levosulfide liquid formulation composition, characterized in that. The levosulfide liquid composition according to claim 8, wherein the pH adjuster is added so that the pH of the levosulfide liquid composition is 7.0 or less. The levosulfide liquid composition according to claim 6, wherein the pH adjusting agent is at least one component selected from the group consisting of sodium hydroxide, potassium hydroxide, prolamine, ammonia water, ammonium carbonate, acetic acid, hydrochloric acid, and phosphates. The levosulfide liquid formulation according to claim 1, which has a formulation of liquid, disposable drink, syrup or gel type. A method for producing a levosulfide liquid composition according to claim 1, comprising the step of dissolving at least one pharmaceutically acceptable acid component in purified water and a step of dissolving levosulpyrid in the solution formed above.