JPH11139970A - Oral solution - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an oral solution reduced in or freed of a bitter taste and an irritant feeling of diclofenac or its salt to a throat. SOLUTION: This oral solution is obtained by carrying out a heating treatment of diclofenac or its salt in the presence of a flavoring agent. The flavoring agent is one or more selected from glycine, glycyrrhetinic acid and salts thereof. The heating treatment is carried out at 50-80 deg.C temperature.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an oral solution of diclofenac in which bitterness and irritation to the throat during administration are reduced or eliminated.

[0002]

2. Description of the Related Art Diclofenac is a drug having excellent analgesic, anti-inflammatory and antipyretic effects, and many tablets and capsules are on the market. However, tablets and capsules have the drawback of being difficult to take for elderly and serious patients,
There has been a demand for an oral solution that is easy to take.

However, diclofenac or a salt thereof has a bitter taste when taken and a strong irritating feeling to the throat,
It was difficult to obtain a good oral liquid preparation.

On the other hand, a method has been disclosed for reducing the bitterness and irritation of diclofenac (Japanese Patent Laid-Open No. 2-17).
No. 8224), even with this method, a satisfactory feeling of ingestion has not been obtained.

[0005]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide an oral liquid preparation in which the bitterness of diclofenac or a salt thereof and the irritating feeling to the throat are reduced or eliminated.

[0006]

Means for Solving the Problems In view of this situation, the present inventors have conducted intensive studies and found that diclofenac or a salt thereof can be heated to a bitter taste in the presence of a flavoring agent,
The present inventors have found that an oral liquid preparation with reduced or eliminated irritation to the throat can be obtained, and completed the present invention.

That is, the present invention provides an oral liquid preparation obtained by heating diclofenac or a salt thereof in the presence of a flavoring agent.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The salt of diclofenac used in the present invention includes: alkali metal salts such as sodium and potassium; alkaline earth metal salts such as calcium and magnesium; ammonium salts; Alkyl metal salts; monoethanolamine, diethanolamine,
Primary, secondary or tertiary such as diisopropanolamine, triethanolamine, triisopropanolamine, etc.
And alkanolamine salts. this house,
Sodium salts are particularly preferred.

[0009] Diclofenac or a salt thereof is used as an oral solution 1
It is preferable to use 0.01 to 1000 mg per mL.

[0010] The flavoring agent used in the present invention includes glycine, glycyrrhizic acid or a salt thereof. Of these, glycyrrhizic acid may be itself or a crude drug containing it. Examples of the salt of glycyrrhizic acid include alkali metal salts such as sodium and potassium, and ammonium salts. The addition amount of glycine, glycyrrhizic acid or a salt thereof is 0.01 per 1 mL of the oral solution.
~ 200mg is preferred, especially 1 ~ 50mg
The degree is preferred.

The oral solution of the present invention may contain, in addition to the above-mentioned components, a thickener, a suspending agent, a buffer, a stabilizer, a preservative, a surfactant, a flavoring agent, etc. which are usually used in an oral solution. May be used.

The oral solution of the present invention has a pH of 1.5 to 1.5.
It is preferable to set it within the range of 5.5, and especially 3.0 to 3.0
It is preferable to be within the range of 5.0.

The oral liquid preparation of the present invention is prepared, for example, by dissolving a preservative, purified sucrose and the like in water, adding a flavoring agent and, if necessary, a thickener and a suspending agent to the solution, and uniformly dispersing or dissolving. Diclofenac or a salt thereof is added, if necessary, a surfactant is added, and this is uniformly dispersed or dissolved.If necessary, the pH is adjusted to the above range with sodium hydroxide or the like, and the mixture can be produced by heating. it can.

The heating treatment is preferably carried out at a temperature of 40 ° C. or higher, particularly preferably in the range of 50 to 80 ° C. The heating time is preferably about 10 to 60 minutes, particularly preferably about 20 to 30 minutes.

[0015]

EFFECT OF THE INVENTION The oral liquid preparation of the present invention has a reduced or eliminated bitter taste of diclofenac and a feeling of irritation to the throat, and has a good feeling of taking.

[0016]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Comparative Example 1 A preservative and purified sucrose were dissolved, and a thickener and a suspending agent were added to the solution to uniformly disperse it. Add diclofenac Na
And a surfactant were added and dispersed uniformly. Thereafter, sodium hydroxide was added to adjust the pH to 6.0, and a fragrance was added. The solution was dispersed more uniformly, and the total amount was
The solution was made up to 00 mL to give an oral solution.

[0018]

(Prescription in 100 mL) Diclofenac Na 750 mg Surfactant (sucrose fatty acid ester) 25 mg Thickener (carboxyvinyl polymer) 400 mg Suspending agent (crystalline cellulose / carmellose sodium) 1 g Purified sucrose 40 g Hydrochloric acid Appropriate amount Water Sodium oxide appropriate amount Preservatives appropriate amount Fragrance trace amount Total amount in purified water 100mL

Comparative Example 2 Sorbic acid and sorbitol solution were dissolved, and hydroxyethyl cellulose and crystalline cellulose / carmellose sodium were added to the solution and uniformly dispersed. Thereafter, ascorbic acid, citric acid and saccharin sodium were added and dispersed uniformly. Diclofenac was added to the solution, and the mixture was further uniformly dispersed, and the amount of the solution was corrected to obtain an oral liquid preparation.

[0020]

(Prescription in 100 mL) Diclofenac 750 mg Hydroxyethyl cellulose 500 mg Crystalline cellulose / carmellose sodium 1.2 g Sorbitol solution 25 g Sorbic acid 50 mg Ascorbic acid 100 mg Saccharin sodium 60 mg Citric acid 200 mg Purified water 100 mL

Example 1 A preservative and purified sucrose were dissolved, and a thickener, a suspending agent, and a flavoring agent (glycine) were added to the solution and uniformly dispersed. To this, diclofenac Na and a surfactant were added and uniformly dispersed. Thereafter, sodium hydroxide was added to adjust the pH to 4.5, and a fragrance was added. The solution was further uniformly dispersed, and the total amount was adjusted to 100 mL with purified water. After this, 70 ° C
For 20 minutes to give an oral solution.

[0022]

(Prescription in 100 mL) Diclofenac Na 750 mg Glycine 50 mg Surfactant (sucrose fatty acid ester) 25 mg Thickener (carboxyvinyl polymer) 400 mg Suspending agent (crystalline cellulose / carmellose sodium) 1 g Purified sucrose 40 g Hydrochloric acid Appropriate amount Sodium hydroxide Appropriate amount Preservatives Appropriate amount Fragrance trace amount Total amount in purified water 100mL

Example 2 A syrup containing the following ingredients was obtained in the same manner as in Example 1.

[0024]

(Prescription in 100 mL) Diclofenac Na 750 mg Glycine 100 mg Surfactant (sucrose fatty acid ester) 25 mg Thickener (carboxyvinyl polymer) 400 mg Suspending agent (crystalline cellulose / carmellose sodium) 1 g Purified sucrose 40 g Hydrochloric acid Appropriate amount Sodium hydroxide Appropriate amount Preservatives Appropriate amount Fragrance trace amount Total amount in purified water 100mL

Example 3 A syrup containing the following ingredients was obtained in the same manner as in Example 1.

[0026]

(Prescription in 100 mL) Diclofenac Na 750 mg Glycyrrhizic acid 50 mg Surfactant (sucrose fatty acid ester) 25 mg Thickener (carboxyvinyl polymer) 400 mg Suspending agent (crystalline cellulose / carmellose sodium) 1 g Purified sucrose 40 g Hydrochloric acid appropriate amount Sodium hydroxide appropriate amount Preservatives appropriate amount Fragrance trace amount Total amount in purified water 100mL

Example 4 A syrup containing the following ingredients was obtained in the same manner as in Example 1.

[0028]

(Prescription in 100 mL) Diclofenac Na 750 mg Glycyrrhizic acid 100 mg Surfactant (sucrose fatty acid ester) 25 mg Thickener (carboxyvinyl polymer) 400 mg Suspending agent (crystalline cellulose / carmellose sodium) 1 g Purified sucrose 40 g Hydrochloric acid appropriate amount Sodium hydroxide appropriate amount Preservatives appropriate amount Fragrance trace amount Total amount in purified water 100mL

Example 5 A syrup containing the following ingredients was obtained in the same manner as in Example 1.

[0030]

Table 7 (Prescription in 100 mL) Diclofenac Na 750 mg Glycine 50 mg Glycyrrhizic acid 50 mg Surfactant (sucrose fatty acid ester) 25 mg Thickener (carboxyvinyl polymer) 400 mg Suspending agent (crystalline cellulose / carmellose sodium) 1 g Purification Sucrose 40g Hydrochloric acid appropriate amount Sodium hydroxide appropriate amount Preservatives appropriate amount Fragrance trace amount

Example 6 A syrup containing the following ingredients was obtained in the same manner as in Example 1.

[0032]

(Prescription in 100 mL) Diclofenac Na 750 mg Glycine 100 mg Glycyrrhizic acid 100 mg Surfactant (sucrose fatty acid ester) 25 mg Thickener (carboxyvinyl polymer) 400 mg Suspending agent (crystalline cellulose / carmellose sodium) 1 g Purification Sucrose 40g Hydrochloric acid appropriate amount Sodium hydroxide appropriate amount Preservatives appropriate amount Fragrance trace amount

Test Example 1 A sensory test was conducted on the above-mentioned specimens by 10 healthy adult volunteers. The sensory evaluation was performed according to the following criteria for bitterness and irritation to the throat.
The results are shown in Tables 9 and 10.

Sensory evaluation of bitterness 1: bitter 2: slightly bitter 3: hardly bitter 4: not bitter at all

Sensory evaluation of feeling of irritation 1: Feel 2: Feel slightly 3: Feel almost no 4: Feel no

[0036]

[Table 9]

[0037]

[Table 10]

As shown in Tables 9 and 10, the addition of glycine or glycyrrhizic acid improved the feeling of taking the oral solution of diclofenac.

Examination of Temperature Conditions The present oral liquid preparation is intended to improve the feeling of ingestion by adding a flavoring agent and heating. Then, the temperature conditions were studied in the following examples.

Example 7 A preservative and purified sucrose were dissolved, and a thickener, a suspending agent, glycine, and glycyrrhizic acid were added to the solution and uniformly dispersed. To this, diclofenac Na and a surfactant were added and uniformly dispersed. Thereafter, sodium hydroxide was added to adjust the pH to 4.5, and a fragrance was added. The solution was further uniformly dispersed, and the total amount was made up to 100 mL with purified water to prepare an oral liquid preparation.

[0041]

(Prescription in 100 mL) Diclofenac Na 750 mg Glycine 100 mg Glycyrrhizic acid 100 mg Surfactant (sucrose fatty acid ester) 25 mg Thickener (carboxyvinyl polymer) 400 mg Suspending agent (crystalline cellulose / carmellose sodium) 1 g Purification Sucrose 40g Hydrochloric acid appropriate amount Sodium hydroxide appropriate amount Preservatives appropriate amount Fragrance trace amount

Example 8 A preservative and purified sucrose were dissolved, and a thickener, a suspending agent, glycine and glycyrrhizic acid were added to the solution and uniformly dispersed. To this, diclofenac Na and a surfactant were added and uniformly dispersed. Thereafter, sodium hydroxide was added to adjust the pH to 4.5, and a fragrance was added. The solution was further uniformly dispersed, and the total amount was adjusted to 100 mL with purified water. After this,
The solution was heated at 40 ° C. for 20 minutes to give an oral liquid preparation.

[0043]

(Prescription in 100 mL) Diclofenac Na 750 mg Glycine 100 mg Glycyrrhizic acid 100 mg Surfactant (sucrose fatty acid ester) 25 mg Thickener (carboxyvinyl polymer) 400 mg Suspending agent (crystalline cellulose / carmellose sodium) 1 g Purification Sucrose 40g Hydrochloric acid appropriate amount Sodium hydroxide appropriate amount Preservatives appropriate amount Fragrance trace amount

Example 9 A syrup containing the same prescription components was obtained in the same manner as in Example 8, except that the corrected heating temperature was changed to 50 ° C.

Example 10 A syrup containing the same prescription components was obtained in the same manner as in Example 8, except that the corrected heating temperature was set to 60 ° C.

Example 11 A syrup containing the same ingredients was obtained in the same manner as in Example 8, except that the corrected heating temperature was 70 ° C.

Example 12 A syrup containing the same formulation was obtained in the same manner as in Example 8, except that the corrected heating temperature was set to 80 ° C.

Test Example 2 The samples shown above were compared by the same test method as in Test Example 1. The results are shown in Tables 13 and 14.

[0049]

[Table 13]

[0050]

[Table 14]

As shown in Tables 13 and 14, by setting the heating treatment temperature to 40 ° C. or higher, particularly to 50 ° C. or higher, the feeling of taking the oral liquid solution of diclofenac was improved.

Claims (3)

[Claims] An oral liquid preparation obtained by heating diclofenac or a salt thereof in the presence of a flavoring agent. 2. The flavoring agent is one or more selected from glycine, glycyrrhizic acid and salts thereof.
The oral solution according to the above. 3. The oral liquid preparation according to claim 1, wherein the heating treatment is performed at a temperature of 50 to 80 ° C.