JP5928331B2 - Dimemorphan-containing oral solution - Google Patents

Description

  The present invention relates to an internal liquid or beverage containing dimemorphan.

  Dimemorphan is an antitussive agent having a morphinan skeleton and has a strong antitussive effect. It is a non-narcotic drug with no central dependence, and is used for upper respiratory tract inflammation, acute bronchitis, and pneumonia. It is also used as a cough syrup for over-the-counter medicines.

  Beverages such as internal preparations are easier to swallow than solid preparations, and have the advantage of being easy to take for people with low swallowing functions such as children and the elderly and people with symptoms such as cough. However, the taste of dimemorphan is bitter, and when it is used as a beverage, the ingestibility is poor from the aspect of flavor. Therefore, it is necessary to reduce the bitterness by using a sweetener such as sugar alcohol and to design it to be easy to drink.

  In the past, methods for improving taste have been developed in order to contain drugs that exhibit bitterness and the like. For example, by using stevia, a composition for colds with improved bitterness such as dihydrocodeine phosphate and carbinoxamine maleate can be produced (see Patent Document 1), and by using erythritol, an oral solution with reduced bitterness of noscapine and bromhexine can be produced. (See Patent Document 2).

  In addition, some antitussive solid preparations that are disintegrated or dissolved in the oral cavity take drugs that have not only bitterness but also throat irritation when taken, but contain mannitol, etc. And the example which reduced the irritability to a throat has been reported (refer patent document 3).

  However, with respect to oral liquid preparations including antitussive agents, although the bitterness has been improved by a known method, the problem of reducing irritation to the throat has not yet been solved. Therefore, an antitussive-containing internal solution or beverage that reduces both bitterness and throat irritation has been demanded.

JP-A-9-52849 Japanese Patent No. 38004337 JP 2004-269513 A

  The inventors of the present invention have confirmed that even when a high concentration of sugar alcohol is added to an internal liquid or beverage containing dimemorphan and / or a salt thereof, bitterness is not reduced and irritation to the throat is not reduced. An object of the present invention is to reduce bitterness and throat irritation peculiar to dimemorphan and / or a salt thereof in an oral solution or beverage.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that dimemorphan and / or its salt-containing oral solution or beverage can be combined with sugar alcohol and / or trehalose and sucralose together to produce dimethylolphan specific. As a result, it was found that the bitterness of the throat can be improved, and further, irritation to the throat can be reduced.

That is, the present invention relates to (1) a) dimemorphan and / or a salt thereof, b) a sugar alcohol and / or trehalose, c) an internal liquid or beverage containing sucralose,
(2) The internal liquid or beverage according to (1) above, wherein b) component is 180 parts by mass or more and c) component is 0.1 parts by mass or more with respect to 1 part by mass of a) component a)
(3) The internal liquid or beverage according to (1) or (2), wherein the sugar alcohol is at least one selected from the group consisting of xylitol, sorbitol, erythritol and maltitol,
It is.

  According to the present invention, it was possible to reduce the bitterness and throat irritation of an internal use liquid preparation or beverage containing dimemorphan and / or a salt thereof.

  Examples of the “dimemorphan salt” of the present invention include salts acceptable as an oral solution or beverage, such as hydrochloride, sulfate, nitrate, phosphate, maleate, and fumarate. Merolphan phosphate.

  As the “sugar alcohol” in the present invention, erythritol, xylitol, maltitol, inositol, sorbitol, mannitol, maltitol and the like can be used, and xylitol and sorbitol are preferable.

  In order to sufficiently exhibit the effects of the present invention, the amount of sugar alcohol and / or trehalose in the present invention (the total amount in the case of 2 or more types) is usually 180 parts by weight or more, preferably 1 part by weight of dimemorphan. Is 184 parts by mass or more, more preferably 230 parts by mass or more, and most preferably 260 parts by mass or more. The blending amount of sucralose at this time is preferably 0.1 parts by mass or more with respect to 1 part by mass of dimemorphan and / or a salt thereof (in the case of blending two or more).

  The “internal liquid preparation” in the present invention is not particularly limited as long as it is a liquid that can be taken internally. Examples thereof include pharmaceuticals such as internal liquids and drinks, and quasi drugs. Examples of the “beverage” include various beverages in the food area such as a nutritional functional food and a food for specified insurance.

  Vitamins, minerals, amino acids, herbal medicines, herbal medicine extracts, caffeine, and the like can be appropriately added to the internal liquid or beverage of the present invention as long as the effects of the present invention are not impaired. In addition, additives such as antioxidants, coloring agents, flavoring agents, flavoring agents, surfactants, solubilizers, preservatives, sugar alcohols, sweeteners other than trehalose, and high-intensity sweeteners other than sucralose as necessary Can be appropriately blended within a range not impairing the effects of the present invention. These additives and the like may be blended singly or in combination of two or more.

  The method for preparing the internal liquid or beverage of the present invention is not particularly limited. Usually, dimemorphan and / or its salt, sugar alcohol and / or trehalose, sucralose, and other ingredients as necessary are dissolved in an appropriate amount of purified water, and then purified water is further added to adjust the volume. Accordingly, by performing filtration and sterilization treatment, it can be provided as a dimemorphan-containing internal solution or beverage.

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

Test Example (1) Preparation of Each Oral Solution or Beverage Each internal solution or beverage of Reference Example 1-3, Example 1-7 and Comparative Example 1-3 shown below was prepared.

Reference example 1
Dimemorphan phosphate 60 mg and xylitol 16000 mg were dissolved in purified water to a total volume of 40 mL.

Reference example 2
Anhydrous caffeine 3.3 mg and xylitol 16000 mg were dissolved in purified water to make a total volume of 40 mL.

Reference example 3
Dimemorphan phosphate 60 mg and xylitol 18000 mg were dissolved in purified water to a total volume of 40 mL.

Example 1
Dimemorphan phosphate 60 mg, xylitol 16000 mg and sucralose 6.6 mg were dissolved in purified water to make a total volume of 40 mL.

Example 2
Dimemorphan phosphate 60 mg, sorbitol 14000 mg and sucralose 6.6 mg were dissolved in purified water to make a total volume of 40 mL.

Example 3
Dimemorphan phosphate 60 mg, xylitol 16000 mg, stevia 7.4 mg and sucralose 4.4 mg were dissolved in purified water to a total volume of 40 mL.

Example 4
Dimemorphan phosphate 60 mg, erythritol 8000 mg and sucralose 4.4 mg were dissolved in purified water to make a total volume of 40 mL.

Example 5
Dimemorphan phosphate 60 mg, maltitol 16000 mg and sucralose 4.4 mg were dissolved in purified water to make a total volume of 40 mL.

Example 6
Dimemorphan phosphate 60 mg, trehalose 16000 mg and sucralose 4.4 mg were dissolved in purified water to make a total volume of 40 mL.

Example 7
Dimemorphan phosphate 60 mg, xylitol 4200 mg, sorbitol 10080 mg, trehalose 1500 mg and sucralose 10.6 mg, stevia 17.7 mg were dissolved in purified water to make a total volume of 40 mL.

Comparative Example 1
Dimemorphan phosphate 60 mg and sucralose 33.3 mg were dissolved in purified water to make a total volume of 40 mL.

Comparative Example 2
Dimemorphan phosphate 60 mg and stevia 110.8 mg were dissolved in purified water to a total volume of 40 mL.

Comparative Example 3
Dimemorphan phosphate 60 mg, xylitol 16000 mg and stevia 22 mg were dissolved in purified water to a total volume of 40 mL.

(2) Test Method Each prepared liquid preparation or beverage was evaluated for bitterness and irritation by four panels based on the evaluation criteria shown in Table 1, and the results are shown in Table 2.

Here, sweetness (%)
Sucrose (sugar) concentration in 100 mL [w / v%]
The sweetness level of 1% corresponds to the sweetness level of a 1% sucrose aqueous solution.
(3) Results

  As shown in Table 2, from the results of Reference Examples 1 and 2, the bitterness could be reduced by adding sugar alcohol to the beverage containing caffeine described as a drug having a bitter taste in the Japanese Pharmacopoeia. On the other hand, it was found that the bitterness could not be reduced even when sugar alcohol was added to the oral solution containing dimemorphan. Moreover, it turned out that the drink containing a dimemorphan has the irritation | stimulation to a throat stronger than the drink containing a caffeine.

  From the results of Reference Example 3, bitterness and irritation to throat are reduced compared to Reference Example 1 even when sugar alcohol is further added to the internal liquid or beverage containing dimemorphan and the sweetness is adjusted to 45%. I found out that it was not.

  From the results of Example 1, it was found that the bitterness and throat irritation were reduced by simultaneously blending sucralose into the internal liquid solution blended with dimemorphan and sugar alcohol. From the results of Comparative Example 1, when sucralose is added to dimemorphan and sucralose is added to adjust the sweetness to the same level as in Example 1, although irritation to the throat is reduced, bitterness may not be reduced. all right. Similarly, from the result of Comparative Example 2, it was found that bitterness was not reduced even when stevia was added to dimemorphan to adjust the sweetness to the same level as in Example 1.

  In addition, from the results of Examples 2, 4, and 5, when bitumen and irritation of dimethylolphan is reduced when sorbitol, erythritol, and maltitol are added as a sugar alcohol in place of the xylitol compounded in Example 1. I understood.

  In addition, from the results of Example 6, it was found that even if trehalose was added instead of the sugar alcohol compounded in Examples 1, 2, 4, and 5, the bitter taste and throat irritation of dimethylmorphane were reduced.

  From the results of Example 3, even if stevia is further added to the internal liquid preparation containing dimemorphan, sugar alcohol and sucralose, bitterness and irritation to the throat are similar to those in Example 1 and can be added. all right.

  From the results of Comparative Example 3, it was found that when stevia was added instead of sucralose added in Example 1, bitterness and throat irritation were not reduced.

  According to the present invention, it has become possible to reduce the bitterness and irritation of the throat of a beverage containing dimethylmorphane, so that it is possible to provide a highly commercialized beverage containing dimethylmorphane in the fields of pharmaceuticals, quasi drugs and foods. it can.

Claims (2)

An internal liquid preparation or beverage containing a) dimemorphan and / or a salt thereof, b) at least one sugar alcohol and / or trehalose selected from the group consisting of xylitol, sorbitol, erythritol, and maltitol, and c) sucralose. The component a) is 0.15% by weight or more with respect to the total amount of the internal solution or beverage, the component b) is 8,000 / 60 parts by mass or more, and the component c) is 1 part by mass of the component a). 4.4 / 60 parts by weight or more of an internal liquid or beverage. An internal liquid preparation or beverage containing a) dimemorphan and / or a salt thereof, b) at least one sugar alcohol and / or trehalose selected from the group consisting of xylitol, sorbitol, erythritol, and maltitol, and c) sucralose. In addition, the a) component is 0.15% by weight or more based on the total amount of the oral solution or beverage, a) the component b) is 180 parts by mass or more, and c) the component is 1 part by mass of the component. 0.1 parts by mass or more der Ru in the clothing solutions or drink.