JP5853461B2 - Oral solution - Google Patents

Description

  The present invention relates to an internal liquid preparation containing loxoprofen or a pharmacologically acceptable salt thereof.

Loxoprofen is a compound having an excellent antipyretic analgesic effect, and tablets or fine granules have already been marketed. Moreover, although provision of a loxoprofen containing liquid agent is desired from the ease of taking, there exists a problem that it has an unpleasant taste.
So far, a syrup preparation containing loxoprofen, a sweetener and cyclodextrin has been reported in Patent Literature (Patent Literature 1). Moreover, although the syrup agent which reduced the gastric mucosal disorder resulting from a loxoprofen is known, there is no description regarding ingestibility (patent document 2, 3).

JP 61-268621 JP2005-139165 JP2006-52210

  It is an object of the present invention to provide a loxoprofen-containing internal liquid that suppresses unpleasant taste and a method for suppressing the unpleasant taste of an internal liquid that contains loxoprofen.

  As a result of intensive investigations to solve the above problems, the present inventors have found that the oral liquid containing loxoprofen or a pharmacologically acceptable salt thereof has an unpleasant taste of the liquid liquid containing loxoprofen by blending guar gum. The inventors have found that it can be suppressed, and have completed the present invention.

That is, the present invention
(1) a) loxoprofen or a pharmacologically acceptable salt thereof, and b) an oral solution characterized by containing guar gum,
(2) The internal use liquid preparation according to (1), wherein loxoprofen or a pharmacologically acceptable salt thereof is a sodium salt of loxoprofen,
(3) The internal liquid preparation according to any one of (1) to (2), wherein the pH is 2.5 to 7.0,
(4) A method for suppressing the unpleasant taste of loxoprofen or a pharmacologically acceptable salt thereof, characterized in that guar gum is added to an oral solution containing loxoprofen or a pharmacologically acceptable salt thereof,
It is.

  According to the present invention, the unpleasant taste of loxoprofen or a pharmacologically acceptable salt thereof can be suppressed.

  Loxoprofen is 2- [4- (2-oxocyclopentan-1-ylmethyl) phenyl] propionic acid, and its pharmacologically acceptable salts are alkali salts such as sodium, potassium and lithium salts. Metal salts; alkaline earth metal salts such as calcium salts and magnesium salts, metal salts such as aluminum salts, iron salts, zinc salts, copper salts, nickel salts and cobalt salts; inorganic salts such as ammonium salts; t-octyl Amine salt, dibenzylamine salt, morpholine salt, glucosamine salt, phenylglycine alkyl ester salt, ethylenediamine salt, N-methylglucamine salt, guanidine salt, diethylamine salt, triethylamine salt, dicyclohexylamine salt, N, N′-dibenzyl Ethylenediamine salt, chloroprocaine salt, procaine salt, diethanola Examples thereof include amine salts such as organic salts such as amine salts, N-benzyl-phenethylamine salts, piperazine salts, tetramethylammonium salts, and tris (hydroxymethyl) aminomethane salts. A sodium salt is preferable.

  The blending amount of loxoprofen or a pharmacologically acceptable salt thereof in the present invention can be appropriately selected and used according to the purpose. For example, it is preferable to blend 10 to 180 mg (converted into free form / anhydride) per day.

Guar gum is a water-soluble natural polysaccharide obtained from the endosperm of guar beans, and is a polysaccharide having one galactose side chain on two mannose molecules linked in a straight chain.
In the internal use liquid preparation of the present invention, the mixing ratio of loxoprofen or a pharmacologically acceptable salt thereof and guar gum is usually 0.01 to 500 parts by mass, preferably 0.03 with respect to 1 part by mass of loxoprofen or a pharmacologically acceptable salt thereof. It is -133 mass part, More preferably, it is 0.06-16.7 mass part, Most preferably, it is 0.4-1.3 mass part.

    The pH of the internal solution according to the present invention is 2.5 to 7.0, preferably 3.0 to 7.0. This is because the acidic range below pH 2.5 is not preferable in terms of the solubility of loxoprofen or a pharmacologically acceptable salt thereof, and the basic range above pH 7.0 is not preferable in terms of flavor. Moreover, the said range is preferable also from the antiseptic effect of an internal use liquid agent being acquired by making pH into an acidic region. Therefore, in order to keep the pH of the oral solution of the present invention in the above range, in the present invention, if necessary, inorganic acids such as hydrochloric acid and phosphoric acid, organic acids such as citric acid and malic acid, sodium hydroxide, etc. An inorganic base or an organic base such as sodium citrate or sodium malate may be blended.

  As other components, the internal liquid preparation of the present invention may appropriately contain vitamins, minerals, amino acids or salts thereof, herbal medicines, herbal extracts, caffeine, royal jelly and the like as long as the effects of the present invention are not impaired. it can.

  Furthermore, if necessary, additives such as antioxidants, colorants, fragrances, flavoring agents, surfactants, solubilizers, preservatives, sweeteners, acidulants are appropriately added within a range not impairing the effects of the present invention. Can be blended.

  The internal liquid preparation of the present invention can be prepared by a conventional method, and the method is not particularly limited. Usually, after each component is taken and dissolved with an appropriate amount of purified water, the pH is adjusted, the remaining purified water is added to adjust the volume, and filtration and sterilization are performed as necessary.

  The internal liquid preparation of the present invention can be applied to pharmaceuticals such as syrups and drinks, quasi drugs and the like.

Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples, and Test Examples.
Table 1 shows examples and Table 2 shows comparative examples. In Examples 1 to 6 and Comparative Examples 1 to 4, loxoprofen sodium, potassium chloride, tartaric acid, and guar gum were dissolved in purified water, pH was adjusted using hydrochloric acid and sodium hydroxide, and purified water was added to the total amount. Was filled in a glass bottle and capped to obtain an internal solution. In Example 7 and Comparative Example 5, loxoprofen sodium, potassium chloride, tartaric acid, and guar gum were dissolved in purified water, the pH was adjusted with hydrochloric acid and sodium hydroxide, and purified water was added to make a total volume of 10 mL. A glass bottle was filled and a cap was applied to obtain an internal solution. In Example 8, loxoprofen sodium, potassium chloride, tartaric acid, guar gum, and sugar are dissolved in purified water, pH is adjusted using hydrochloric acid and sodium hydroxide, and purified water is added to make a total volume of 30 mL, which is filled into a glass bottle. A cap was applied to obtain an internal solution. Comparative Examples 6 to 9 were prepared using PVP, soy polysaccharide, sodium alginate, and chondroitin sulfate polymer in place of guar gum, and Comparative Example 10 was prepared in the same manner as in Examples 1 and 2 using sugar instead of guar gum. .

試験方法
25〜40歳までの4人をパネルとして、試験液約20ｍＬを服用し、調製直後のロキソ
プロフェンの不快味について評価した。なお、一つのサンプルを評価した後は、温湯
で口中をすすぎ、十分経過してから次の試験液の評価を行った。
評価基準
実施例１〜３、比較例６〜１０の評価はグアーガムを配合していない比較例１との相対評価を行い、実施例４は比較例２、実施例５は比較例３、実施例６は比較例４、実施例７は比較例５、実施例８は比較例１０との相対評価を行った。
実施例１〜３、比較例６〜１０の評価は、比較例1に比べて「非常に弱く不快味を感じる」を−３点、「弱く不快味を感じる」を−２点、「やや弱く不快味を感じる」を−１点、「同等に不快味を感じる」を０点、「やや強く不快味を感じる」を１点、「強く不快味を感じる」を２点、「非常に強く不快味を感じる」を３点とし、結果を平均値で求めた。実施例４〜８はそれぞれの比較例の評価点を０点とし、比較例に比べ「非常に弱く不快味を感じる」を−３点、「弱く不快味を感じる」を−２点、「やや弱く不快味を感じる」を−１点、「同等に不快味を感じる」を０点、「やや強く不快味を感じる」を１点、「強く不快味を感じる」を２点、「非常に強く不快味を感じる」を３点とし、結果を平均値で求めた、表３および表４に評価点として示した。

Test method
Four persons from 25 to 40 years old took a panel and took about 20 mL of the test solution to evaluate the unpleasant taste of loxoprofen immediately after preparation. After evaluating one sample, the mouth was rinsed with warm water, and the next test solution was evaluated after sufficient time had passed.
Evaluation criteria Examples 1 to 3 and Comparative Examples 6 to 10 were evaluated relative to Comparative Example 1 in which no guar gum was blended, Example 4 was Comparative Example 2, Example 5 was Comparative Example 3, and Example. Relative evaluation with Comparative Example 4 was performed with Comparative Example 4, Comparative Example 5 with Example 7, and Comparative Example 10 with Example 8.
The evaluation of Examples 1 to 3 and Comparative Examples 6 to 10 is -3 points for "Very weak and unpleasant taste", -2 for "Weak and unpleasant taste", and "Slightly weak" -1 points for "I feel unpleasant taste", 0 points for "Equally unpleasant taste", 1 point for "Slightly unpleasant taste", 2 points for "I feel strong unpleasant taste", "Very strong unpleasantness" “Taste is felt” was given 3 points, and the results were obtained as average values. In Examples 4 to 8, the evaluation score of each comparative example was set to 0, compared to the comparative example, “very weak and unpleasant taste” was −3 points, “weak and unpleasant taste” was −2 points, “slightly -1 points for "Weak and uncomfortable taste", 0 points for "Equally unpleasant taste", 1 point for "Slightly unpleasant taste", 2 points for "Strongly feel unpleasant taste", "Very strong “I feel unpleasant taste” was given 3 points, and the results were obtained as average values.

As apparent from Tables 3 and 4, when guar gum was added, the unpleasant taste of loxoprofen sodium was suppressed. On the other hand, in Comparative Examples 6 to 9 containing other polymers, the effect of improving the unpleasant taste was not obtained. Further, as apparent from Comparative Example 10, the effect of masking unpleasant taste was not obtained even when sugar was added.

  INDUSTRIAL APPLICABILITY The present invention can be used for the production of an internal liquid preparation containing loxoprofen or a pharmacologically acceptable salt thereof having good dosing properties.

Claims (4)

An internal solution containing a) loxoprofen or a pharmacologically acceptable salt thereof and b) guar gum. The internal use liquid agent of Claim 1 whose loxoprofen or its pharmacologically acceptable salt is the sodium salt of loxoprofen. pH is 2.5-7.0, The internal use liquid agent of any one of Claims 1-2. A method for producing an internal liquid solution in which the unpleasant taste of loxoprofen or a pharmacologically acceptable salt thereof is suppressed , which comprises blending guar gum with an internal liquid solution containing loxoprofen or a pharmacologically acceptable salt thereof.