JP5853459B2 - 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 studies in order to solve the above-mentioned problems, the present inventors have found that the oral solution containing loxoprofen or a pharmacologically acceptable salt thereof is combined with the oral solution containing gum arabic, thereby discomforting the internal solution containing loxoprofen. The inventors found that the taste 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 containing gum arabic powder,
(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 use liquid agent of any one of (1)-(2) whose pH is 2.5-7.0,
(4) A method for suppressing the unpleasant taste of loxoprofen or a pharmacologically acceptable salt thereof, which comprises blending gum arabic powder with an oral solution containing loxoprofen or a pharmacologically acceptable salt thereof,
It is.

  ADVANTAGE OF THE INVENTION By this invention, the unpleasant taste of the internal use liquid agent containing a loxoprofen or its pharmacologically acceptable salt 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.

  Gum arabic powder is a water-soluble polysaccharide whose main component is arabinogalactan, and refers to gum gum extract obtained by cutting into trunks and branches of other trees from Africa such as Acacia sengal or Acacia. Although more than 700 kinds of these trees are known, gum arabic that can be used in the present invention may be derived from any tree. Arabinogalactan is composed of arabinose, rhamnose, glucuronic acid, galactose and protein, and has a low viscosity due to its spherical structure.

  In the internal use liquid preparation of the present invention, the mixing ratio of loxoprofen or a pharmacologically acceptable salt thereof and gum arabic powder is usually 0.01 to 500 parts by mass with respect to 1 part by mass of loxoprofen or a pharmacologically acceptable salt thereof, preferably Is 0.03 to 133 parts by mass, more preferably 0.06 to 16.7 parts by mass, and most preferably 0.5 to 5 parts by mass.

  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 1-6 and Comparative Examples 1-4, loxoprofen sodium, potassium chloride, tartaric acid, and gum arabic powder are dissolved in purified water, pH is adjusted using hydrochloric acid and sodium hydroxide, and purified water is added. The total amount was 30 mL, filled into a glass bottle, and capped to obtain an internal solution. In Example 7 and Comparative Example 5, loxoprofen sodium, potassium chloride, tartaric acid, and gum arabic powder were dissolved in purified water, pH was adjusted using hydrochloric acid and sodium hydroxide, and purified water was added to make a total volume of 10 mL. Then, a glass bottle was filled and a cap was applied to obtain an internal solution. In Example 8, loxoprofen sodium, potassium chloride, tartaric acid, gum arabic powder, and sugar were dissolved in purified water, pH was adjusted using hydrochloric acid and sodium hydroxide, and purified water was added to make a total volume of 30 mL. The solution was filled with a cap and an internal solution was obtained. Comparative Examples 6 to 9 were prepared in the same manner as in Examples 1 and 2, using PVP, soybean polysaccharide, sodium alginate, and sodium chondroitin sulfate in place of gum arabic powder. Comparative Example 10 was prepared in the same manner as in Examples 1 to 3 except that sugar was added instead of gum arabic powder.

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 standards Examples 1 to 3 and Comparative Examples 6 to 10 were evaluated relative to Comparative Example 1 in which no gum arabic powder was blended, Example 4 was Comparative Example 2, and Example 5 was Comparative Example 3. Example 6 was compared with Comparative Example 4, Example 7 was compared with Comparative Example 5, and Example 8 was compared with Comparative Example 10.
In Examples 1 to 3 and Comparative Examples 6 to 10, “very weak and unpleasant taste” is −3 points, “weak and unpleasant taste” is −2 points, “slightly unpleasant taste” -1 points for "feels uncomfortable", 0 points for "feeling uncomfortable taste equally", 1 point for "feeling slightly unpleasant taste", 2 points for "feeling strongly unpleasant taste", "very strong unpleasant taste" The result was obtained as an average value. In Examples 4 to 7, 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 unpleasant taste", 0 points for "Equally unpleasant taste", 1 point for "Slightly unpleasant taste", 2 points for "Strongly feel unpleasant taste", "Very strong “I feel an unpleasant taste” was given 3 points, and the results were obtained as average values. Tables 3 and 4 show the evaluation points.

As is apparent from Tables 3 to 4, the unpleasant taste of loxoprofen sodium was suppressed when the gum arabic powder was blended. 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) gum arabic powder. 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. Manufacture of an oral liquid preparation in which unpleasant taste of loxoprofen or a pharmacologically acceptable salt thereof is suppressed , characterized by blending gum arabic powder with an internal liquid liquid containing loxoprofen or a pharmacologically acceptable salt thereof Way .