KR20050055812A - The medicine composition of masking unpleasant taste - Google Patents

Abstract

The present invention relates to a method for masking the taste of an oral liquid preparation having an unpleasant taste, and more particularly, to a liquid preparation containing ibuprofen, dexibuprofen, acetaminophen or leprotropizin having an unpleasant taste. Rodextrin solution, water-soluble amino acid or derivatives thereof are used alone or in mixture of one or more to mask the unpleasant taste of the main drug to improve the dose.

Description

The medicine composition of masking unpleasant taste}

Liquid formulations that are usually taken orally include unpleasant tastes, such as chemical and metallic tastes, including bitter taste, which adversely affects the dose and affects the expression of the drug. Therefore, the improvement of taste for oral compositions using the active ingredient showing an unpleasant taste, including the main bitter taste of the main drug has been constantly progressing. Methods have been attempted to mask substances that cause the unpleasant taste of various oral compositions using compounds or mixtures of compounds such as spices or sugars or sweeteners. Gelatin (Japanese Patent 04-346, 937) / gelatinized starch (Japanese Patent 04-235, 136); Acidic amino acids (US Pat. Nos. 4,517,379 and Japanese Patents 05-015, 389 and 05-004, 921); Chitosan (Japanese Patent 04-009, 335); Cyclodextrin (US Pat. No. 5,024,997); Liposomes (US Pat. No. 5,009,819); Lecithin or lecithin material (Japanese Patent No. 62-265, 234); Surfactants (US Pat. No. 5,439,671); Salts (US Pat. No. 5,262,179) and the like have been used to mask the unpleasant taste of oral compositions. Likewise, coating or microencapsulation (European Patent 551,820); Functional group changes (US Pat. No. 5,350,839); And taste masking in the form of structural matrices have been used. Oral compositions using this technique include silicate clays (US Pat. Nos. 3,140,978 and 4,581,232) in an effort to further provide compositions with improved taste; Acrylic acid copolymers (US Pat. No. 5,286,489); Gum (US Pat. No. 5,288,500); Cellulose (US Pat. No. 5,192,563); And reagents such as waxes. In addition, other methods for suppressing or reducing bitterness have been disclosed. For example, Kurtz and Fuller have disclosed a method for improving certain compounds to mask the taste by blocking the unpleasant taste when added to a composition containing an unpleasant taste (US Pat. No. 5,232,735 and PCT Patent WO 93/10677). ). Roy et al. Disclosed N- (sulfomethyl) -N'-arylurea as a sweetness and bitterness inhibitor (US Pat. Nos. 4,994,490 and 5,266,717). Guadagni et al. Have found that addition of flavones and neodiosmine may cause a decrease in bitterness and off-after-taste (US Pat. No. 4,154, 862), and Riemer is a bitter compound of certain cinnamic acid derivatives. It has been found to have the ability to inhibit the bitter taste and aftertaste of artificial sweeteners (US Pat. No. 5,336,513). Magnolato applied a method of removing bitterness from fruit and vegetable extracts by selective adsorption using inexpensive natural wood materials (US Pat. No. 4,282,264), and Miller used steam to remove bitterness from soybean (US Pat. No. 4,248,141). number).

An ideal solution for reducing bitter taste would be the development of a general bitter inhibitor that does not affect the overall flavor of the oral composition. Katsuragi and Kurihara are described in Nature, vol. 365, pp. 213-214, 1993, published bitter inhibitors made with phosphatidic acid and β-lactoglobulin that inhibit the taste response and sensation to bitter substances without affecting the response to other taste stimuli. Unfortunately, these compounds have shown only limited success in suppressing the bitter taste of many different bitter compounds.

In general, the following items must be considered to prepare liquid formulations.

(1) Content uniformity of the active ingredient: Since the conventional liquid formulation is to take the corresponding amount according to each age or body weight, only a certain amount of the active ingredient can be administered only if the active ingredient is evenly distributed in the base. In addition, in the case of suspension syrups such as ibuprofen and acetaminophen, when the active ingredient precipitates over time or forms a crystal upon recrystallization at the top of the syrup, there is a lack of content uniformity, resulting in an unstable drug expression after administration. There is a need to ensure the stability of the formulation.

(2) Prevention of the growth of microorganisms: It contains water and sugars, and liquid preparations are stored at room temperature for 1 ~ 36 months even after opening, and there is a possibility of microbial contamination and propagation. In order to exhibit the optimum activity of the liquid solution of pH 3-7 is required.

(3) Medication compliance: Since the liquid formulation will taste on the tongue, in the case of preparations with an unpleasant taste, such as bitterness of the active ingredient, the medication compliance of the patient is poor. Therefore, in order to mask such a taste, a taste adjusting material such as a sweetener should be used.

Herein, in order to increase the compliance of patients in the preparation of liquid formulations with stability, safety, and efficacy, an oral pharmaceutical liquid composition for shielding unpleasant tastes such as bitterness, spicy taste, and burning sensation is prepared.

The present invention relates to a method for suppressing an unpleasant taste by adding a cyclodextrin solution and a water-soluble amino acid or a derivative thereof alone or in mixture of one or more thereof to an oral composition containing an active ingredient exhibiting pharmacological activity. The present invention is also suitable for the treatment of acute bronchitis containing ibuprofen, dexibuprofen with a bitter and metallic taste, a fever containing acetaminophen, a composition for the treatment of pain, and a leprotropyzin with bitterness and burning sensation. Relates to a pharmaceutical composition of taste.

 Therefore, the present inventors conducted intensive research to find ingredients that can improve the taste of ibuprofen and acetaminophen, targeting various additives that are used as pharmaceutical additives, and ensure safety in human use as food and pharmaceutical additives. Studies have been conducted with single or mixtures of cyclodextrins and water-soluble amino acids or derivatives thereof known to have been known.

Cyclodextrins, ie, cyclodextrins α, β or γ or their complexes, have been introduced into the field of formulation of synthetic drugs under other names such as Shardinger dextrins, Cycloamyloses and Cyclologcans. It has been applied to dissolution aids such as prostaglandins, steroids and barbitals, chemical stabilizers such as aspirin, epinephrine and vitamins, and taste and odor improving agents such as prostaglandins and alkyl parabens. Generally used cyclodextrin solution is a complex of cyclodextrin α, β, and γ types, produced by the action of an enzyme called cyclodextrin transglycosidase in a medium containing starch, and has an LD50 value of 10 g / It is reported to be a high value of more than kg, and because only a small amount is absorbed in the gastrointestinal tract, it is a material with little safety and safety.

The water-soluble polymer material is at least one selected from sodium carboxymethylcellulose, tragacanth gum, xanthan gum, agar and alginic acid.

The inventors have combined cyclodextrin liquids, water-soluble polymers, water-soluble amino acids or derivatives thereof alone or in one or more mixtures, especially sodium glutamate, in specific ratios to provide ibuprofen, dexibuprofen or acetaminophen syrup over a long period of time. The present invention was completed to confirm that it can mask the unpleasant taste that has been a problem in formulating, and can effectively prevent the formation of precipitation.

 Accordingly, the present invention relates to ibuprofen, dexibuprofen, acetaminophen, levodropropidol syrup which is improved in taste, characterized in that it contains cyclodextrin solution and sodium el-glutamate, and which is prevented from precipitating in circulation.

More specifically, an object of the present invention is to prevent the formation of precipitates by adding 0.1 to 5% w / v% of cyclodextrin solution, 0.1 to 0.5% of sodium glutamate, and 0.05 to 5 w / v% of a water-soluble polymer material, thereby making the formulation unpleasant. It is to provide a syrup that is masked bitter taste. When the cyclodextrin solution is added in an amount of less than 0.1w / v% and less than 0.05w / w%, the desired effect is not sufficiently exhibited in the present invention, since the cyclodextrin solution is a viscous liquid as a homologue of cyclic oligosaccharides. If the cyclodextrin solution exceeds 5w / v%, the liquid may be around the bottle cap during preparation, causing the cap to be difficult to pick up, and crystals may precipitate and become cloudy during cooling. On the other hand, in order to prevent precipitation, a good result can be obtained by adding a water-soluble polymer material in the range of 0.1 w / v% to 5w / v%. If the amount exceeds 5w / v%, the viscosity is high and the flowability is not good, which makes it difficult to take the product. Preferably, the cyclodextrin solution contains 1 to 4 w / v% and 0.1 to 1 w / v% of a water-soluble polymer.

According to the present invention, the cyclodextrin liquid, sodium glutamate and water-soluble polymers are combined in the above ratios to provide an advantage that the masking effect of the unpleasant taste is significantly superior compared to the case of using each component alone.

Example

The following examples describe and explain embodiments in more detail within the scope of the present invention. The following examples are appended for illustrative purposes only, and many variations are possible without departing from the spirit and scope of the invention, but should not be construed as limiting the invention.

ingredient Example 1 (w / v%) Example 2 (w / v%) Example 3 (w / v%) Example 4 (w / v%) Example 5 (w / v%) Example 6 (w / v%) Ibuprofen 2 ~ 4 2-4 - - - - Acetaminophen - - 3.2 3.2 - - Dexpropene - - - - 1 ~ 2 - Draw Propine - - - - - 0.6 Agar 0.3 - 0.2 - - - Xanthan Gum - 0.2 - 0.2 0.2 - High fructose 26 25 32 15 25 24 Sorbitol Liquid 24 25 26 20 25 10 White sugar 40 40 42 40 40 15 Cyclodextrin 3 3 3 3 3 3 El Sodium Glutamate 0.2 0.2 0.2 0.2 0.2 0.1 Cremophor RH 40 0.1 0.2 0.1 - 0.2 - kaoline One - One - - - Citric acid 0.25 0.25 0.019 0.019 0.25 0.2 Sodium citrate 0.19 0.19 - - 0.19 0.02 Pigment 0.0015 0.0015 0.013 0.013 0.0015 - Flavor 0.1 0.1 0.1 0.1 0.1 0.2 Preservative 0.1 0.1 0.1 0.1 0.1 0.1 Purified water q.s. q.s. q.s. q.s. q.s. qs

Purified water, high fructose, sorbitol liquid, white sugar, cyclodextrin liquid, sodium el-glutamate and preservatives are prepared according to the composition described in the above examples and mixed with augmented agar or xanthan gum and then pigments, flavoring agents and pigments are added. Thereafter, ibuprofen, dexibuprofen, acetaminophen or a drop of propropigin and kaolin are dispersed in the preparation. Thus prepared formulations were visually and taste tested for changes in precipitation and taste after 3 days, 7 days, 14 days, and 1 month while preserving in a life tester at 40 ° C. In all of the examples, no precipitation occurred and the unpleasant taste peculiar to the main ingredient was also masked in taste.

According to the pharmaceutical composition according to the present invention as described above, it improves the taste of the liquid formulation containing the active substance having a pharmacological activity with an unpleasant taste.

 In addition, the oral pharmaceutical composition according to the present invention increases the compliance with the medication by reducing the objection to taking the patient.

 In addition, the pharmaceutical composition according to the present invention increases the efficiency of the use of the drug and allows an appropriate drug evaluation.

Claims (6)

A method for making an oral composition containing an unpleasant flavor drug taste good, the present invention relates to a pharmaceutical composition containing a cyclodextrin solution and a water-soluble amino acid or a derivative thereof alone or in mixture of one or more thereof.      2. A pharmaceutical composition according to claim 1, characterized by sodium glutamate in water soluble amino acids or derivatives thereof alone or in a mixture of one or more. The oral composition of claim 1, wherein the oral composition is selected from the group consisting of pharmaceutical compositions, and an unpleasant taste can be felt from the group consisting of bitterness, spicy taste, burning sensation, and mixtures thereof, to which cyclodextrin liquid and sodium glutamate are added. Pharmaceutical composition, characterized in that to mask the taste The liquid preparation according to claim 1, which contains 0.1 to 5.0 w / v% of cyclodextrin liquid and 0.1 to 0.5 w / v% of sodium glutamate. 2. A liquid formulation according to claim 1, wherein cyclodextrin liquid and sodium elglutamate are added to the formulation containing ibubrofen, dexbrofen, acetaminophen, or levobropropizin. The liquid pharmaceutical composition for oral use according to claim 5, wherein the liquidity of the composition has a pH of 3 to 7.