JP6350157B2 - Internal liquid - Google Patents

Description

  The present invention relates to an internal solution containing dimemorphan and can be applied to the field of pharmaceuticals.

  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 general drugs.

  The internal solution is easier to swallow than a solid preparation, and has the advantage that it is easy to take for people with low swallowing function such as children and the elderly and people with symptoms such as cough. However, dimemorphan has a very strong irritating bitter taste, and when taken as a liquid, the ingestion is reduced. Therefore, it is necessary to reduce bitterness and make it easier to drink by using sweeteners.

  Until now, methods for improving the taste of bitter drugs having a morphinan skeleton have been developed. For example, by using stevia, a composition for common cold with improved bitterness of dihydrocodeine phosphate can be produced (see Patent Document 1), sugar alcohol and / or trehalose, and sucralose are blended together to form dimemorphanline. An internal solution (see Patent Document 2) that improves the bitterness of acid salts has been reported.

  However, although the bitterness suppressing effect is recognized by these known methods, it is not sufficient for suppressing the stimulating bitter taste of dimemorphan.

JP-A-9-52849 WO2011 / 148794 gazette

  An object of the present invention is to provide a liquid preparation for internal use that suppresses the very strong bitterness of dimemorphan and is easy to take.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that the above-mentioned problems can be solved by adding a specific fragrance in an internal solution containing dimemorphan, and the present invention has been completed. It was.

  Furthermore, as a result of intensive studies on the aroma component to solve the above-mentioned problems, the present inventors have found that perilaldehyde or citronellyl acetate is a component that can suppress the bitter taste peculiar to dimemorphan.

That is, the present invention
a) Dimemorphan and / or a salt thereof, and b) selected from the group of kumquat flavor, yuzu flavor, orange flavor, grapefruit flavor, honey flavor, grape flavor, corn flavor, caramel flavor, perilla flavor, perilaaldehyde and citronellyl acetate. A liquid preparation for internal use, comprising at least one of a fragrance or a fragrance component.

  INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a liquid preparation for internal use which is greatly suppressed from the very pungent bitterness derived from dimethylmorphane and can be easily taken. ADVANTAGE OF THE INVENTION By this invention, the dimemorphan liquid mixture which has a strong antitussive action can be provided as a formulation which is easy to drink.

  In the present invention, the salt of dimemorphan includes salts acceptable as internal solutions such as hydrochloride, phosphate, sulfate, fumarate, maleate, and the most preferable is phosphate. . The content of dimemorphan and / or a salt thereof in the internal use liquid preparation of the present invention is 0.025 to 0.25 w / v%.

  In the present invention, the kumquat flavor means a kumquat-specific flavor, and may be any of natural, semi-synthetic and synthetic flavors, and is generally available as kumquat flavor or kumquat essence. it can. Also, kumquat juice, recovered flavor, kumquat oil, and kumquat extract may be used.

  In the present invention, the yuzu flavor means a yuzu-flavored flavor, and may be any natural, semi-synthetic or synthetic flavor, and is generally obtained as a yuzu flavor or yuzu essence. it can. Moreover, a yuzu fruit juice, collection | recovery flavor, a yuzu oil, and a yuzu extract may be sufficient.

  In the present invention, the orange flavor means a flavor unique to orange, and may be any flavor of natural products, semi-synthetic products, and synthetic products, and is generally obtained as orange flavor or orange essence. it can. Further, orange juice, recovered flavor, orange oil, and orange extract may be used.

  In the present invention, the grapefruit flavor means a grapefruit-specific flavor, and may be any of natural, semi-synthetic and synthetic flavors, and is generally obtained as a grapefruit flavor or a grapefruit essence. it can. Further, it may be grapefruit juice, recovered flavor, grapefruit oil, or grapefruit extract.

In the present invention, honey flavor means a honey-specific flavor, and may be any natural, semi-synthetic, or synthetic flavor, and is generally available as a honey flavor or honey essence. it can. Moreover, a honey extract may be sufficient.

In the present invention, the grape flavor means a flavor having a unique flavor of grape, and may be any flavor of natural products, semi-synthetic products, and synthetic products, and is generally obtained as a grape flavor or a grape essence. it can. Moreover, a grape juice, collection | recovery flavor, and a grape extract may be sufficient.

In the present invention, “kokuto flavor” means a flavor having a unique flavor of brown sugar, and may be any of natural, semi-synthetic, and synthetic flavors, and is generally obtained as a kokuto flavor or a kokutokosensu. can do.

In the present invention, the caramel flavor means a caramel-specific flavor, and may be a natural product, a semi-synthetic product, or a synthetic product, and is generally obtained as a caramel flavor or a caramel essence. it can.

In the present invention, the perilla flavor means a flavor unique to perilla, and may be any of natural, semi-synthetic and synthetic flavors, and is generally obtained as perilla flavor or perilla essence. it can. Further, it may be a recovered flavor or perilla extract.

Among the fragrances selected from the group of kumquat flavor, yuzu flavor, orange flavor, grapefruit flavor, honey flavor, grape flavor, corn flavor, caramel flavor, and perilla flavor of the present invention, preferred from the viewpoint of the effect of the present invention. A kumquat flavor, a yuzu flavor, a corn flavor, and a caramel flavor are most preferred, and a kumquat flavor and a yuzu flavor are most preferred.

  The content of kumquat flavor, yuzu flavor, orange flavor, grapefruit flavor, honey flavor, grape flavor, corn flavor, caramel flavor or perilla flavor in the internal preparation of the present invention is 0.05 to 0.2 w / v%. Is preferred.

  Perilaldehyde, which is an aromatic component of the present invention, is a main component of yuzu, but is a known component having a perilla scent. It can be obtained by synthesis, extraction, purification or the like by a known method. Commercial products may also be used. The content of perilaldehyde in the internal liquid preparation of the present invention is preferably 0.0001 part by mass or more with respect to 1 part by mass of the dimemorphan and / or salt thereof of the present invention.

  Citronellyl acetate which is an aroma component of the present invention is a main component of kumquat. It can be obtained by synthesis, extraction, purification or the like by a known method. Commercial products may also be used. The content of citronellyl acetate in the internal liquid preparation of the present invention is preferably 0.0001 part by mass or more with respect to 1 part by mass of the dimemorphan and / or salt thereof of the present invention.

  In order to keep the pH of the internal solution of the present invention in the range of 2.5 to 7.0, preferably in the range of 3.0 to 6.0, the pH adjuster is necessary. Can be blended. Examples of the pH regulator include organic acids such as citric acid, malic acid, tartaric acid, fumaric acid, lactic acid, succinic acid, ascorbic acid, and acetic acid, and salts thereof, inorganic acids such as hydrochloric acid and phosphoric acid, and salts thereof. Can be mentioned. These pH regulators can be used alone or in combination.

  In addition, the liquid preparation for internal use of the present invention includes components other than those described above, such as antitussives other than dimemorphan, expectorants, antipyretic analgesics, antihistamines, sweeteners, storage, in a qualitative and quantitative range that does not impair the effects of the present invention. Ingredients generally used for liquids for internal use such as agents, colorants, pH adjusters, solubilizers, antioxidants, fragrances and solvents can be blended.

  The liquid preparation for internal use according to the present invention can be prepared by a conventional method, and the method is not particularly limited. Usually, each component is mixed with purified water of a specified amount or less, the volume is adjusted to a specified amount, and filtration is performed as necessary. It can be obtained by sterilization.

  The internal solution of the present invention can be applied to pharmaceutical products such as an internal solution containing a syrup.

  EXAMPLES Next, although an Example demonstrates this invention in detail, this invention is not limited to these Examples.

  Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples, and Test Examples, but the present invention is not limited to these Examples.

(1) Production of liquid for internal use:
The internal use liquid agent shown in Table 1 and Table 2 was manufactured. The following components were dissolved in an appropriate amount of purified water, adjusted to pH 4.5 with citric acid and sodium citrate, and further purified water was added to make 100 mL. These were filled in glass bottles and capped to obtain internal liquids (Examples 1 to 7, Comparative Examples 1 to 6).

Test Example 1: Sensory evaluation The internal use liquids of Examples 1 to 7 and Comparative Examples 1 to 6 were evaluated by 3 specialist panels using the evaluation items and evaluation criteria shown in Table 3 below. It is shown in Table 2.

  As shown in Tables 1-2, kumquat flavor, yuzu flavor, orange flavor, grapefruit flavor, honey flavor, and the liquid preparations of Examples 1 to 7 added with other flavors were compared with Comparative Examples 1 to 6 with other flavors added. It was a result that the bitterness suppression effect was large in comparison. In particular, the kumquat flavor and the yuzu flavor had a high bitterness-inhibiting effect derived from dimemorphan.

(2) Production of internal solution:
Internal liquid preparations shown in Tables 4 and 5 were produced. The following components were dissolved in an appropriate amount of purified water, adjusted to pH 4.5 with citric acid and sodium citrate, and further purified water was added to make 100 mL. These were filled in a glass bottle and capped to obtain an internal solution (Examples 8 to 17, Comparative Example 7).

  Sensory evaluation: The flavors of the internal solutions of Examples 8 to 17 and Comparative Example 7 were evaluated in the same manner as in Test Example 1, and the results are shown in Tables 4 and 5.

  As shown in Table 4, perilaldehyde or citronellyl acetate suppressed the bitter taste derived from dimemorphan.

  As shown in Table 5, the liquid preparation to which a sweet flavor or caramel flavor was added suppressed the bitterness derived from dimethylmorphane.

  According to the present invention, it is possible to reduce the irritation bitterness of a liquid preparation for internal use containing dimemorphan, and therefore it is possible to provide a liquid product containing dimemorphan having a high commercial value.

Claims (1)

a) Dimemorphan and / or a salt thereof, and b) selected from the group of kumquat flavor, yuzu flavor, orange flavor, grapefruit flavor, honey flavor, grape flavor, corn flavor, caramel flavor, perilla flavor, perilaaldehyde and citronellyl acetate. A liquid for internal use, comprising at least one of a fragrance or a fragrance component.