Oral composition

Abstract

To provide an oral composition containing mequitazine, while achieving a reduction in the strong bitter aftertaste peculiar to mequitazine.SOLUTION: An oral composition containing mequitazine is blended with erythritol and / or xylitol, thereby achieving a reduction in the strong bitter aftertaste peculiar to mequitazine.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an oral composition that contains mequitazine while reducing the strong aftertaste that is characteristic of mequitazine. [Background technology]

[0002] Mequitazine is a phenothiazine antihistamine used to treat allergies, rhinitis, etc. Mequitazine is available in tablet form, syrup and granule form, and is also suitable for use in children.

[0003] Mequitazine has a bitter taste, and it is desirable to improve the taste in order to improve the ease of administration. For example, Patent Document 1 discloses that the ease of administration can be improved by forming a film-like preparation in which a water-swellable gel-forming layer containing acesulfame potassium or sucralose is laminated on both sides of a drug-containing layer containing mequitazine. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2009-007310 A Summary of the Invention [Problem to be solved by the invention]

[0005] The film-form preparation of Patent Document 1 solves the taste problem by devising a dosage form, and therefore the bitterness of mequitazine cannot be sufficiently masked in a general dosage form (i.e., a mixture of the compounding components of a pharmaceutical composition). In particular, with a general dosage form, a strong bitterness remains as an aftertaste after taking the drug, so there is still a lot of room for improvement in the taste of mequitazine preparations.

[0006] Therefore, an object of the present invention is to provide an oral composition that contains mequitazine while reducing the strong bitter aftertaste that is characteristic of mequitazine. [Means for solving the problem]

[0007] As a result of intensive research, the present inventors have found that by mixing erythritol or xylitol with an oral composition containing mequitazine, the strong bitter aftertaste peculiar to mequitazine is reduced, unlike the case of mixing other flavoring agents. Furthermore, by further mixing phenylephrine with an oral composition containing mequitazine, the bitterness becomes even stronger, and other flavoring agents cannot sufficiently mask not only the bitter aftertaste but also the bitter initial taste. However, by mixing erythritol or xylitol, the strong bitter aftertaste and initial taste peculiar to mequitazine can be effectively masked. The present invention has been completed based on these findings and through further research.

[0008] That is, the present disclosure provides the inventions of the following aspects. Item 1. An oral composition containing (A) mequitazine and (B) erythritol and / or xylitol. Item 2. The oral composition according to Item 1, further comprising (C) phenylephrine and / or a salt thereof. Item 3. The oral composition according to Item 1 or 2, wherein the content of the component (A) is 0.05 to 0.25% by weight. Item 4. The oral composition according to any one of Items 1 to 3, wherein the content of the component (B) is 200 parts by weight or more per part by weight of the component (A). Item 5. The oral composition according to any one of Items 2 to 4, wherein the content of the component (C) is 3 to 15 parts by weight or more per part by weight of the component (A). Item 6. The oral composition according to any one of Items 1 to 5, which is in the form of a powder, fine granules, granules, troches, drops, chewable tablets, dry syrup, lozenges, drinks, suspensions, or syrups. Effect of the Invention

[0009] According to the present invention, there is provided an oral composition which contains mequitazine while reducing the strong bitter aftertaste characteristic of mequitazine. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The oral composition of the present disclosure contains (A) mequitazine (hereinafter also referred to as "component (A)") and (B) erythritol and / or xylitol (hereinafter also referred to as "component (B)"). The oral composition of the present disclosure may further contain (C) phenylephrine and / or a salt thereof (hereinafter also referred to as "component (C)").

[0011] (A) Mequitazine The oral composition of the present disclosure contains mequitazine as component (A). Mequitazine is a known drug as an antihistamine. The mequitazine used in the present disclosure may be mequitazine that complies with the Japanese Pharmacopoeia, and may be produced by a known method or may be commercially available.

[0012] The content of the (A) component in the oral composition of the present disclosure is not particularly limited, and may be, for example, 0.05 to 0.25% by weight. From the viewpoint of reducing the strong bitter aftertaste peculiar to mequitazine, the content is preferably 0.05 to 0.22% by weight, more preferably 0.05 to 0.18% by weight, and even more preferably 0.05 to 0.15% by weight. Since the oral composition of the present disclosure is highly effective in reducing the strong bitter aftertaste peculiar to mequitazine, even if the content of the (A) component is relatively high, the bitter aftertaste can be effectively reduced. From this viewpoint, the preferred content of the (A) component in the oral composition of the present disclosure is 0.06 to 0.25% by weight, more preferably 0.09 to 0.25% by weight, and even more preferably 0.11 to 0.25% by weight.

[0013] (B) Erythritol and / or xylitol The oral composition of the present disclosure contains erythritol and / or xylitol as component (B). Component (B) can reduce the strong bitter aftertaste that is specific to component (A). In addition, when the oral composition of the present disclosure further contains component (C), component (B) can also reduce the even stronger bitterness caused by the combination of components (A) and (C).

[0014] In the oral composition of the present disclosure, either erythritol or xylitol may be used as component (B), or a combination of these may be used. From the viewpoint of further enhancing the effect of reducing bitterness, erythritol is preferably used as component (B).

[0015] In the oral composition of the present disclosure, the content of the component (B) is not particularly limited and may be appropriately set depending on the desired level of bitterness reduction effect.

[0016] For example, the content of the (B) component is, for example, 200 parts by weight or more per part by weight of the (A) component, and from the viewpoint of further enhancing the bitterness reducing effect, preferably 250 parts by weight or more, 300 parts by weight or more, or 320 parts by weight or more, more preferably 350 parts by weight or more, 360 parts by weight or more, 370 parts by weight or more, 380 parts by weight or more, 400 parts by weight or more, or 440 parts by weight or more, and even more preferably 470 parts by weight or more, 500 parts by weight or more, 510 parts by weight or more, 520 parts by weight or more, or 530 parts by weight or more. The content of the (B) component is not particularly limited in its upper limit, and the content per part by weight of the (A) component is, for example, 800 parts by weight or less, 700 parts by weight or less, 650 parts by weight or less, 620 parts by weight or less, 580 parts by weight or less, 560 parts by weight or less, 550 parts by weight or less, or 540 parts by weight or less.

[0017] The specific content of the (B) component in the oral composition of the present disclosure is, for example, 26% by weight or more, and from the viewpoint of further enhancing the effect of reducing bitterness, preferably 33% by weight or more, 39% by weight or more, or 42% by weight or more, more preferably 46% by weight or more, 47% by weight or more, 48% by weight or more, 49% by weight or more, 52% by weight or more, or 57% by weight or more, and even more preferably 61% by weight or more, 65% by weight or more, 66% by weight or more, 68% by weight or more, or 69% by weight or more. The specific content of the (B) component is not particularly limited in its upper limit, but may be 90% by weight or less, 85% by weight or less, 81% by weight or less, 75% by weight or less, 73% by weight or less, 72% by weight or less, or 71% by weight or less.

[0018] (C) Phenylephrine and / or its salts The oral composition of the present disclosure contains phenylephrine and / or a salt thereof as component (C). When components (A) and (C) are co-formulated in an oral composition, the bitterness is further enhanced, but the oral composition of the present disclosure effectively reduces the bitterness even when component (C) is co-formulated.

[0019] Phenylephrine and its salts are known drugs as adrenergic agonists. The phenylephrine and / or its salts used in the present disclosure may be mequitazine according to the Japanese Pharmacopoeia, and may be produced by a known method or may be commercially available.

[0020] The salt of phenylephrine is not particularly limited as long as it is pharma- ceutically acceptable, and examples thereof include salts of inorganic acids such as hydrochloride, hydrobromide, and phosphate, and salts of organic acids such as acetate, oxalate, malonate, succinate, fumarate, maleate, lactate, malate, citrate, tartrate, phenolphthalein salt, and carbonate, and the like, with hydrochloride being particularly preferred.

[0021] The content of the (C) component in the oral composition of the present disclosure is not particularly limited, but may be, for example, 0.2 to 2% by weight. From the viewpoint of reducing the bitterness of the oral composition, it is preferably 0.2 to 1.8% by weight, more preferably 0.2 to 1.5% by weight, and even more preferably 0.2 to 1.1% by weight. Since the oral composition of the present disclosure has a high effect of reducing bitterness, even if the amount of the (C) component is relatively high, it can effectively reduce the bitter aftertaste. From this viewpoint, the suitable content of the (C) component in the oral composition of the present disclosure is 0.4 to 2% by weight, more preferably 0.5 to 2% by weight, and even more preferably 0.9 to 2% by weight.

[0022] In the oral composition of the present disclosure, the content of the (C) component per part by weight of the (A) component is not particularly limited, and may be, for example, 3 to 15 parts by weight. From the viewpoint of reducing the bitterness of the oral composition, the content is preferably 3 to 10 parts by weight, and more preferably 3 to 8 parts by weight. Since the oral composition of the present disclosure has a high effect of reducing bitterness, even if the co-blending ratio of the (C) component is relatively high, the bitter aftertaste can be effectively reduced. From this viewpoint, the suitable content of the (C) component per part by weight of the (A) component is 5 to 15 parts by weight, more preferably 6 to 15 parts by weight, even more preferably 7 to 15 parts by weight, and even more preferably 7.5 to 15 parts by weight.

[0023] Other Ingredients The oral composition of the present disclosure may or may not contain additives and / or bases according to the formulation form in addition to the above-mentioned (A) and (B) components, and the (C) component that is optionally blended. The additives and bases that may or may not be contained are not particularly limited as long as they are pharma- ceutically acceptable, and include excipients, binders, disintegrants, lubricants, isotonicity agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, glossing agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV protection agents, preservatives, flavorings, fragrances, powders, thickeners, dyes, chelating agents, etc. These additives may be used alone or in combination of two or more. The contents of these additives and bases are appropriately set depending on the types of additives and bases used, the formulation form of the oral composition of the present invention, and the like.

[0024] As a specific component of the additive and base, particularly preferred is starch. When starch is blended, the amount of starch in the oral composition of the present disclosure is, for example, 15 to 65% by weight, preferably 20 to 55% by weight, further preferably 24 to 45% by weight, and more preferably 26 to 35% by weight.

[0025] Furthermore, the oral composition of the present disclosure may or may not further contain other nutritional components and / or pharmacological components as necessary. The nutritional components and / or pharmacological components, which may or may not be contained, are not particularly limited as long as they are pharmacologic acceptable, and examples thereof include antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, antiemetic agents, antitussive agents, expectorants, anti-inflammatory enzyme agents, antipyretic analgesic agents (e.g., aspirin, aluminum aspirin, acetaminophen, ethenzamide, sasapirin, salicylamide, sodium salicylate, lactylphenetidine, ibuprofen, etc.). , ketoprofen, etc.), sympathomimetic components other than component (C) (e.g. pseudoephedrine, phenylpropanolamine, ephedrine, etilefrine, methoxamine, midodrine, methoxyphenamine, salts thereof, etc.), antihistamines other than component (A), caffeines, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal powders and / or herbal extracts, vitamins (vitamin A, vitamin B, vitamin C, etc.). These nutritional components and pharmacological components may be used alone or in combination of two or more. The content of these components is appropriately set depending on the type of component to be used, etc.

[0026] Formulation The formulation form of the oral composition of the present disclosure is not particularly limited as long as it can be administered orally, and examples thereof include solid formulations such as powders, granules, troches, drops, chewables, dry syrups, lozenges, tablets, pills, capsules, etc.; semi-solid formulations such as jellies; and liquid formulations such as drinks, suspensions, syrups, etc. When the oral composition of the present disclosure is in a solid or semi-solid dosage form, the (A) component and the (B) component, as well as the (C) component that is blended as necessary, are mixed with each other, and do not form a structure in which each component is blended in a different layer or phase (for example, a multi-layer structure or a coated particle structure).

[0027] Since the oral composition of the present disclosure has an excellent bitterness reducing effect, preferred examples of the above-mentioned formulations, which allow the oral composition to easily come into direct contact with the tongue, include powders, fine granules, granules, troches, drops, chewable tablets, dry syrups, electuaries, drinks, suspensions, and syrups, and more preferred examples include powders, fine granules, and granules.

[0028] Manufacturing method The oral composition of the present invention may be prepared by formulating the above-mentioned components in accordance with a conventional formulation technique used in the pharmaceutical field.

[0029] dose The dose of the oral composition of the present disclosure is not particularly limited, but the daily dose may be, for example, 0.5 to 5 mg / day, preferably 1 to 4 mg / day, more preferably 2 to 4 mg / day of the component (A) and / or, for example, 2 to 50 mg / day, preferably 5 to 40 mg / day, more preferably 5 to 30 mg / day of the component (C), and these doses may be taken, for example, 2 to 3 times a day, preferably 3 times a day. Thus, the dose taken at one time may be 1 / 3 to 1 / 2 times, preferably 1 / 3 times, of the above dose. EXAMPLES

[0030] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0031] Test Example (1) Preparation of oral compositions The components were uniformly mixed in the proportions shown in Tables 1 and 2 to prepare granules of an oral composition.

[0032] (2) Evaluation of bitterness suppression effect Five expert panelists evaluated the level of bitterness (i.e., bitterness felt on the tongue 5 seconds after ingestion) and bitterness aftertaste (i.e., bitterness felt on the tongue 90 seconds after ingestion) for 1 g of each of the prepared oral composition granules. The evaluation criteria were a visual analog scale (VAS) in which the bitterness of the oral composition of Comparative Example 7 was scored as 1 and no bitterness was scored as 10. The scores obtained for each oral composition were averaged and rounded to the nearest whole number to obtain the evaluation value. A rating of 5 or more was considered to be a pass. The results are shown in Tables 1 and 2.

[0033] [Table 1]

[0034] [Table 2]

[0035] As shown in Tables 1 and 2, when the oral composition containing the component (A) was mixed with the component (B) (Examples 1 to 7), the strong bitter aftertaste specific to mequitazine was reduced, unlike when other flavoring agents were mixed (Comparative Examples 2 to 6, 8, and 9). In addition, when the oral composition containing the component (A) was mixed with the component (B) (Examples 1 to 7), not only the bitter aftertaste but also the initial bitter taste was reduced excellently. Among the components (B), the bitterness reduction effect was particularly high when erythritol was used.

[0036] Furthermore, when the oral composition containing the component (A) (Comparative Example 1) was further mixed with the component (C), the bitterness became even stronger (Comparative Example 7), and the enhanced bitterness was so remarkable that even the addition of sucralose or acesulfame K, which had a high initial taste improvement effect when the component (C) was not included among other flavoring agents (Comparative Examples 5 and 6), could not sufficiently mask even the initial bitter taste. Even in the oral composition in which the components (A) and (C) having such a significant bitterness were co-formulated, when the component (B) was added (Examples 6 and 7), it was confirmed that the oral composition had an excellent bitterness reduction effect in both the initial taste and the aftertaste, which was comparable to the oral composition in which the component (C) was not co-formulated (Examples 3 and 5).

[0037] Prescription Examples Granules of oral compositions were prepared by uniformly mixing the components in the ratios shown in Table 3. As a result of testing the oral compositions of each formulation example at a single dose (1 g), it was confirmed that, as in Examples 6 and 7, the compositions had excellent bitterness reduction effects in both initial and aftertastes compared to the case where component (B) was not included.

[0038] [Table 3]

Claims

1. An oral composition comprising (A) mequitazine and (B) erythritol and / or xylitol.

2. The oral composition according to claim 1 , further comprising (C) phenylephrine and / or a salt thereof.

3. The oral composition according to claim 1, wherein the content of the component (A) is 0.05 to 0.25% by weight.

4. The oral composition according to claim 1 , wherein the content of the component (B) is 200 parts by weight or more per part by weight of the component (A).

5. The oral composition according to claim 2, wherein the content of the component (C) is 3 to 15 parts by weight per part by weight of the component (A).

6. 2. The oral composition according to claim 1, which is in the form of a powder, fine granules, granules, troches, drops, chewable tablets, dry syrup, electuary, drink, suspension or syrup.

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