JPH05124963A - Theophylline-containing liquid agent - Google Patents

Abstract

PURPOSE:To provide an oral liquid agent composition comprising theophylline, etc., and sodium bicarbonate, etc., in a specific ratio, having a reduced bitter taste, capable of being readily orally used for infants, and useful for broncho dilators, etc. CONSTITUTION:The objective oral liquid agent composition contains theophylline or its salt and sodium bicarbonate and/or sodium carbonate in a molar ratio of 1/1 to 1/20, and further contains a glutamate salt in a theophylline/glutamate salt molar ratio of 1/0.05 to 1/2.5. The concentration of the theophylline is preferably 0.4-4.0wt.%, and the composition is preferably prepared in the shape of a solution or suspension.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a theophylline-containing preparation, and more particularly to an oral liquid composition in which the bitterness of the drug is reduced by solubilizing or suspending theophylline, which is a poorly soluble drug.

[0002]

Theophylline is a drug used as a bronchodilator for the treatment of bronchial asthma and heart failure. However, theophylline is poorly soluble, sucrose fatty acid ester is a conventionally known solubilizer, propylene glycol, polyvinylpyrrolidone, even with the use of concentrated glycerin, theophylline can not be sufficiently dissolved, It was very difficult to prepare as a solution. Also, since theophylline has a very strong bitterness,
There is a problem that even a dilute liquid drug is difficult to take for infants and children due to strong bitterness. As theophylline-solubilized preparations, theophylline sodium glycine elixir and the like are known, but since these contain alcohol, application to children is not preferable.

[0003]

DISCLOSURE OF THE INVENTION Therefore, the present invention contains the theophylline, which is a poorly soluble drug, at a high concentration and reduces the bitterness of theophylline without using alcohol. The purpose is to provide an oral liquid composition. The inventor
After making diligent efforts to solve the above problems, it was found that the theophylline-containing liquid preparation in the solution state or the suspension state obtained by blending theophylline with sodium hydrogen carbonate and / or sodium carbonate has a remarkably weak bitterness. The invention was completed. That is, the present invention provides an oral liquid composition containing theophylline or a salt thereof and sodium hydrogen carbonate and / or sodium carbonate, and the molar ratio of theophylline and the sodium salt is in the range of 1: 1 to 1:20. It is a thing. Furthermore, the inventor
The present invention has been completed by finding that the bitterness of theophylline in the obtained liquid preparation composition disappears almost completely by adding glutamate to the above liquid preparation composition. That is, according to the present invention, there is provided an oral liquid composition in which glutamate is further added to the above liquid composition, and the molar ratio of theophylline and glutamate is 1: 0.05 to 1: 1.
A liquid composition is provided in the range of 2.5.

The liquid composition of the present invention is an aqueous liquid composition in the form of a solution or suspension containing theophylline in water in a proportion of 0.4 to 4.0% by weight. Theophylline contained in the liquid composition of the present invention is a drug listed in the 12th revision of the Japanese Pharmacopoeia and can be easily obtained. The theophylline used in the present invention may be in a free form, a salt form, or a hydrate thereof. As the salt, for example, in addition to sodium salt, ethylenediamine salt, allylamine salt, allylglucamine salt and the like can be used, and aminophylline which is a hydrate of ethylenediamine salt can also be used. Of these, it is preferable to use free theophylline.

The composition of the present invention is a composition containing sodium hydrogen carbonate and / or sodium carbonate in a molar ratio of 1: 1 to 1:20 with respect to theophylline.
By adding the above sodium salt in this range,
The sparingly soluble theophylline is sufficiently solubilized into a solution state. Depending on the amount of theophylline added, theophylline is not completely dissolved and a part thereof exists in a suspended state, but an aqueous composition in such a suspended state is also included in the scope of the present invention. Furthermore, the bitterness of theophylline is significantly reduced by adding the sodium salt in the above-mentioned addition amount. If the amount of the sodium salt is less than the above range, theophylline which is the main ingredient is precipitated in the case of a solution, or the bitterness cannot be suppressed, and if the amount of the sodium salt exceeds the above range, the taste is deteriorated. It causes the inconvenience. Sodium hydrogen carbonate and sodium carbonate may be used alone, respectively, or may be used in combination. Of these, sodium hydrogen carbonate is preferably used alone.

The composition of the present invention may further contain glutamate. The composition of the present invention containing glutamate is preferred because the theophylline bitterness is almost completely eliminated. Examples of glutamate include sodium salt, potassium salt, and a mixture thereof. These glutamate salts have a molar ratio of theophylline to glutamate in the range of 1: 0.05 to 1: 2.5,
Preferably, it may be added in the range of 1: 0.0625 to 1: 2.5.

The pH of the composition of the present invention is not particularly limited, but in the case of a solution, it is generally adjusted to a pH of 7 to 9, preferably 7.8 to 8.7. The composition of the present invention, in addition to the above components, D-sorbitol, saccharin sodium, aspartame, sweeteners such as monoammonium glycyrrhizinate, methyl paraoxybenzoate, ethyl paraoxybenzoate, preservatives such as propyl paraoxybenzoate, Flavors such as orange essence, strawberry essence, lemon essence, vanilla essence, peppermint essence, and pH adjusting agents that are organic acids such as citric acid and ascorbic acid can be added as necessary. The amounts of these components to be blended may be within the range well known to those skilled in the art and may be the amounts used for the production of general solutions and suspensions. The composition of the present invention may contain a liquid component such as glycols, if necessary.

The liquid composition of the present invention is preferably prepared in a form suitable for oral administration. As such a form, for example, solution, suspension, solution syrup,
Examples include suspension syrups and the like. These formulations are manufactured by methods well known to those skilled in the art using formulation ingredients that are pharmaceutically acceptable to those skilled in the art. Examples of the formulation components include titanium oxide, magnesium metasilicate aluminate, tragacanth powder, and mixtures thereof, suspending agents such as hydroxypropyl cellulose, sodium carboxymethyl cellulose, and mixtures thereof. Examples of preparation as syrups and suspensions are given below, but the composition of the present invention is not limited to the following embodiments. Syrup Theophylline 0.4-2.0 g Sodium hydrogencarbonate 0.5-4.0 g Sweet saccharide 10-60 g Sodium glutamate 0.05-4.0 g Perfume Suitable amount Add purified water 100 ml Suspension Theophylline 0.4 〜4.0g Sodium hydrogencarbonate 0.5〜4.0g Sweet saccharide 10〜60g Sodium glutamate 0.05〜4.0g Suspending agent 0.3〜2.0g pH adjuster Appropriate amount Total volume 100ml

[0009]

INDUSTRIAL APPLICABILITY The composition of the present invention is remarkably reduced in the bitterness peculiar to theophylline, and since it does not contain alcohol, it is suitable for children and is clinically useful.

[0010]

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. Example 1 0.8 g of theophylline and 1.0 g of sodium hydrogen carbonate were added with purified water to about 70% of the total amount, and heated to dissolve. Then D-sorbitol 20g, saccharin sodium 0.0
4 g, sodium glutamate 0.05 g, hydroxymethyl cellulose 0.017 g and vanilla essence as a fragrance are added and dissolved, and purified water is added to bring the total amount to 100 ml.
And Example 2 A theophylline syrup preparation (pH 8.4) having the following formulation was produced according to Example 1.

Theophylline 0.8 g Sodium carbonate 1.0 g D-sorbitol 20.0 g Sodium saccharin 0.04 g Sodium glutamate 0.05 g Fragrance Suitable amount 100 ml Total amount 100 ml As a comparative example, the following samples were prepared. Comparative Example 1 (solution) Theophylline 0.8 g Purified water was added to a total amount of 100 ml Example 3 (solution) Theophylline 0.8 g Sodium hydrogencarbonate 1.0 g Purified water was added to a total amount of 100 ml Example 4 (solution) Agent) Theophylline 0.8 g Sodium hydrogencarbonate 1.0 g Sodium glutamate 0.05 g Total amount with purified water 100 ml Comparative Example 2 (suspension agent) Theophylline 1.0 g Titanium oxide 0.2 g Magnesium metasilicate aluminate 0.3 g Tragacanth powder 0.3 g Total amount by adding purified water 100 ml Example 5 (suspension agent) Theophylline 1.0 g Titanium oxide 0.2 g Magnesium aluminometasilicate 0.3 g Tragant powder 0.3 g Sodium hydrogencarbonate 0.75 g Purified water was added to a total amount of 100 ml Example 6 (suspension agent) Theophylline 1.0 g Titanium oxide 0.2 g Metaalumina silicate Nesium 0.3 g Tragacanth powder 0.3 g Sodium hydrogen carbonate 0.75 g Sodium glutamate 0.1 g Total amount of purified water 100 ml Example 7 (suspension agent) Theophylline 1.0 g Titanium oxide 0.2 g Metakei Acid Magnesium aluminate 0.3 g Tragacanth powder 0.3 g Sodium hydrogen carbonate 0.75 g Sodium glutamate 0.1 g D-sorbitol 20.0 g Sodium saccharin 0.1 g Citric acid 0.2 g Purified water is added to make the total amount. 100 ml Example 8 (solution) Theophylline 0.8 g Sodium carbonate 1.26 g Purified water was added to make the total amount 100 ml Example 9 (solution) Theophylline 0.8 g Sodium hydrogencarbonate 0.5 g Sodium carbonate 0.63 g Purification The bitterness was evaluated by 10 healthy adults in Examples and Comparative Examples in which water was added and the total amount was 100 ml or more. The results are shown in Table 1 below.

[0012]

[Table 1] Test Examples Unbearable Unbearable but not bitter Example 1 0 4 6 Example 2 0 6 4 Comparative Example 1 10 0 0 Example 3 0 10 0 Example 4 0 7 3 Comparative Example 2 2 8 0 Example 5 0 10 0 Example 6 0 6 4 Example 7 0 0 10 Example 8 0 10 0 Example 9 0 10 0 From the above results, the liquid composition of the present invention markedly attenuated the bitterness of theophylline. It is clear that

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Claims (4)

[Claims] 1. An oral liquid composition comprising theophylline or a salt thereof and sodium hydrogen carbonate and / or sodium carbonate, wherein the molar ratio of theophylline and the sodium salt is in the range of 1: 1 to 1:20. 2. Further comprising glutamate, the molar ratio of theophylline to glutamate is 1: 0.05 to 1: 1.
The oral liquid composition according to claim 1, which is in the range of 2.5. 3. The oral liquid composition according to claim 1, wherein the concentration of theophylline is 0.4 to 4.0% by weight. 4. A solution or suspension form.
Or the oral liquid composition according to 2.