JPH0256416A - Granule with suppressed bitterness - Google Patents

Abstract

PURPOSE:To obtain a granule, containing aspartame as a flavoring agent, capable of masking active ingredients having bitter taste with sweetness of the aspartame and having low toxicity without bitterness in administration, carcinogenicity, mutagenicity and unpleasant feeling of aftertaste. CONSTITUTION:A granule obtained by adding aspartame expressed by the formula (alpha-L-aspartyl-L-phenylalanine methyl ester) as a flavoring agent in an amount of 1-5% based on an active ingredient. The above-mentioned compound is a dipeptide in which aspartic acid is bound to phenylalanine and an artificial synthetic compound having carboxyl group of the phenylalanine converted into methyl ester. The aspartame having a rapid disintegration degree of the active ingredient within about 3min has great inhibitory effects on bitterness.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a granule preparation that suppresses the bitter taste that remains in the cavity when an antipyretic analgesic is taken, for example.

[Prior Art] It is widely known that cold medicines, antipyretics, analgesics, and the like are currently used in granular formulations.

Compared to powders, granules have the advantages of being non-scattering, fluid and convenient for dispensing, making bulky drugs easier to take, and being cheaper than tablets. Furthermore, granules disintegrate more quickly than tablets, and their dispersion reduces disintegration time, leading to the development of a variety of granules due to their major advantages of shortening the disintegration time and exerting their medicinal effects quickly.

In order to give desirable physical properties to the granule preparation, excipients such as potato starch, lactose, and mannitol, and disintegrants such as carboxymethyl cellulose calcium are added to the granule preparation, and it is particularly retained in the vaginal opening and has a short disintegration time. The taste of the active ingredient spreads directly into the vaginal opening. For example, sweeteners and flavorings are added to reduce the bitterness. Among sweeteners, white sugar is the most widely used, but other sugars such as mannitol and fructose are also used.

[Problems to be Solved by the Invention] However, with the above-mentioned saccharides such as white sugar, mannitol, and fructose, the bitter taste of the active ingredient in the granule preparation remains during the day, and discomfort remains for a long time after taking it. Other sweeteners such as xylit, glucose, and dipotassium glycyrrhizinate lack sweetness and produce a bitter taste immediately after taking. Also, with the artificial sweetener saccharin, the bitter taste of saccharin itself remains during the day.

This is thought to be because the above-mentioned white sugar, mannitol, fructose, xylit, glucose, dipotassium glycyrrhizinate, etc. have insufficient masking effect on bitterness.

Methods using cyclodextrin, which is a masking agent, cannot be prescribed due to restrictions on the amount added.

Therefore, an object of the present invention is to obtain a granule preparation that does not leave a bitter taste in the vaginal opening when taken, even if the active ingredient has a bitter taste.

[? Means for Solving Problem A] In the granules with suppressed bitterness according to the present invention, aspartame is added as a flavoring agent.

[Effect] In the present invention, the sweet taste of aspartame masks the bitter active ingredient, so that when using nIl, no bitterness is felt, or at least no aftertaste remains.

Aspartame (α-aspartyl-phenylalanine methylnisder) used in the present invention is a compound having the following structure.

Aspartame is an artificial sweetener discovered in 1965, and is a dipeptide consisting of aspartic acid and phenylalanine, which is an artificially synthesized compound in which the carboxyl nor of phenylalanine is converted into a methyl ester. Toxicity is extremely low, and neither carcinogenicity nor mutagenicity has been recognized. Alone, it is nearly 200 times sweeter than sugar, has a taste similar to sugar, and has a less unpleasant aftertaste.

[Example] Specific examples of the present invention and comparative examples corresponding to each example are shown below. In addition, if the sweetness level is 1 for white sugar, the same amount of aspartame for rice is 180, the same amount of sodium saccharin is 200, and the same amount of dipotassium glycyrrhizinate is 3.
Using 00 as a standard of conversion, a comparative example with almost corresponding sweetness level was created.

Example 1 77to1 Minophenone 7lyl Isobutyl 7 Cetyl Urea Sodium benzoate Caffeine Peony extract Potato starch Lactose D-Mannitol Carboxymethyl 7ylulose Calcium 25.0 parts 4.2 parts 1.7 parts 4.2 parts 1.4 parts 20.7 parts 20.0 parts 20.0 parts 2.0 parts 7 Subartame Example 2 7 Seto 7 Minophenone Chlorpheniramine maleate al-taa Methylephedrine Noscapine; Kenki caffeine Potato starch Lactose Roman nitol Carboxymethylcellulose calcium 7 Subartame Example 3 1 Heptadamine phenone Chlorpheniramine maleate Dextromethorphan/phenol hook phosphoric acid Potassium guaiacol sulfonate Anhydrous caffeine Potato starch Lactose D-Mannitol Carboxymethylcellulose calcium 7 Subaru Tame Comparative Example 1 0.8 parts 25.0 parts 0.2 parts 1.7 parts 1.3 parts 2.1 parts 22.2 parts 22.0 parts 22.0 parts 2.0 parts 1.5 parts 25. 0 0.14 +, 7 6.7 2.1 22.12 21.0 21.0 2.0 0.34 7ceto7minophenone 7lylisobrovir 7cetyl urea Sodium benzoate Caffeine Cinnamon Paeony extract Barine Starch Lactose D-Mannitol Carboxymethyl Cellulose Calcium Saccharin Sodium Comparative Example 2 7 Cetaminophenone Maleic acid Rolf y Niramine dl-+! Acid Methylephedrine Noscapine Anhydrous Caffeine Bare Soyodenbum Lactose D-Mannitol Carboxymethyl Cellulose Calcium Glycyrrhizin Acid Dipotassium Comparative Example 3 Ayato 7 Minophenone Maleic Acid O Lupheniramine Text a Metorphan Phenol Hooklin Salt 25
．． 0 parts 4.2 parts 1.7 parts 4.2 parts 1.4 parts 20.8 parts 20.0 parts 20.0 parts 2.0 parts 0.7 parts 25.0 parts 0.2 parts 1.7 parts 1.3 parts 2.1 parts 22.8 parts 22.0 parts 220 parts 20 parts 0.9 parts 25.0 parts 0.14 parts 1.7 parts Potassium guaiacol sulfonate
6.7 Part Potato Denbun
3.26 parts carboxymethyl heptylulose calcium 2.0 parts white I
Part J 61.2 Granule formulations having the compositions of Examples 1 to 3 and Comparative Examples 1 to 3 above were prepared, and bitterness suppression was conducted in a blinded manner using a panel of six random subjects. We conducted an effectiveness comparison test. The results are shown in Table 1.

(Hereinafter, blank spaces) From the table, it was confirmed that the granules according to the present invention suppressed bitterness better than other sweeteners, and also reduced unpleasant aftertaste.

Example 2 added about 1% aspartame to the active ingredient, and Example 3 added about 5% aspartame, but if the amount is less than 1%, the effect of suppressing the bitterness of active ingredients such as acetaminophenone is low. Furthermore, it is known that even if aspartame is added in an amount of 5% or more based on the active ingredient, the bitterness suppressing effect remains at 5%.

In addition, the degree of disintegration of pharmaceutical granules is determined to be within 30 minutes, but in the case of the granules according to the present invention, due to the relationship between the masking effect of aspartame and the bitterness of the active ingredient in the granules, It is expected that the faster the degree of disintegration within about 3 minutes, the higher the effect of suppressing the bitterness of aspartame. In other words, if the degree of disintegration of the active ingredient is as slow as 30 minutes, the bitterness will not remain during the day and there is no need to add a sweetener as a flavoring agent, and if the degree of disintegration is about 6 to 10 minutes, the masking effect of aspartame This is because the bitter taste of the active ingredient will spread in your mouth after it disappears.

As described above, in the present invention, the bitter active ingredient is masked by the sweetness of aspartame, and the bitterness is not felt when taking it, or at least it does not remain in the aftertaste. Therefore, it is also possible to take it without water.

In addition, since the amount of Albus steam added is small, it does not cause tooth decay as it causes tooth decay, and it is also low in calories and can be safely used by diabetic patients.

[Effects of the Invention] As explained above, the present invention has the effect that even if the active ingredient has a bitter taste, it is possible to obtain a granule preparation that does not leave a bitter taste in the vaginal opening when taken.

Agent: Patent Attorney Tadashi Sato

Claims (3)

[Claims] (1) Granules with suppressed bitterness characterized by the addition of aspartame as a flavoring agent. (2) The granules with reduced bitterness according to claim 1, wherein aspartame as the flavoring agent is contained in an amount of 1% to 5% based on the active ingredient. (3) The granule with reduced bitterness according to claim 1 or 2, wherein the active ingredient is an antipyretic and analgesic ingredient.