JP5896806B2 - Oral composition - Google Patents

Description

  The present invention relates to an internal composition, particularly methylephedrine or a salt thereof, and an internal composition containing pseudoephedrine or a salt thereof.

In recent years, the necessity of improving the quality of life (QOL) has been emphasized. In the medical field, in connection with improvement of patient QOL, in addition to safety and effectiveness, medicines are required to be easy to take. Conventionally, it has been a matter of course for patients to take patience even if they are bitter or difficult to take. However, in the case of a medicine that imposes a burden on the patient when taking such medicine, the medication instruction is not observed, and as a result, an appropriate therapeutic effect may not be obtained. Therefore, if the medicinal effects are the same, it is desirable that a preparation that is easy to take is not only because the burden on the patient is reduced, but also that compliance (medication compliance) is improved and the planned therapeutic effect is achieved. It is natural from the point of view. For these reasons, provision of pharmaceutical preparations that are easy to take is desired.
There are many ingredients that have bitterness. For example, methylephedrine or a salt thereof and pseudoephedrine or a salt thereof also fall under this category.
Methylephedrine or a salt thereof (particularly methylephedrine hydrochloride) has a mechanism of action similar to that of ephedrine, that is, an alpha action and a beta action, and is known to have bronchodilator action and central antitussive action. It is a known compound.
Pseudoephedrine or a salt thereof (eg, pseudoephedrine hydrochloride) is a known compound that has a vasoconstrictive action due to sympathetic α action and is known to suppress redness and swelling of the nasal mucosa.
As a matter of course, a preparation containing both has a stronger bitterness than a preparation containing each of them alone.
As a method for facilitating taking such a bitter component, a method of adding a sweetener or a corrigent to the bitter component and formulating it is commonly used. This is a method based on the principle of cheating bitterness with sweetness, etc., if expressed in a simple manner. In addition, as another method, a method in which a component having bitterness is coated with a sugar coating and formulated, and a method in which it is encapsulated in a formulation are also commonly used. This is a method based on the principle that the ingredient having bitterness is prevented from coming into contact with the tongue that feels bitter.

16th revision Japanese Pharmacopoeia commentary, Yodogawa Shoten, C-4812

In the method of formulating by adding a sweetening agent or a corrigent to a component having bitterness, the bitterness may not necessarily be sufficiently suppressed because the bitterness is merely cheated by sweetness. In some cases, it may become an unpleasant taste.
In the case of a method of coating a component having bitterness with a sugar coating and a method of encapsulating and formulating in a capsule, a sugar coating step and an encapsulation step are required, respectively. When the amount of the internal composition to be taken is increased, there is a problem that the preparation becomes large or the number of the preparations to be taken increases, making it difficult to take.
Therefore, a bitter suppression method different from the conventional method is required as a method that replaces these methods or a method that supplements these methods.
An object of the present invention is to provide a preparation containing methylephedrine or a salt thereof, and pseudoephedrine or a salt thereof, wherein the bitumen caused by methylephedrine or a salt thereof and pseudoephedrine or a salt thereof is suppressed. And

The inventors surprisingly found that
By further adding mequitazine having bitterness to one or more selected from the group consisting of (A) methylephedrine and a salt thereof, and (B) one or more selected from the group consisting of pseudoephedrine and a salt thereof, Has been found to be reduced, and the present invention has been completed.

That is, this invention provides the aspect etc. of a postscript.
Item 1.
(A) One or more types selected from the group consisting of methylephedrine and its salts (B) One or more types selected from the group consisting of pseudoephedrine and its salts, and (C) an internal use composition containing mequitazine.
Item 2.
The internal use composition of said claim | item 1 which is a powder, a fine granule, a granule, an uncoated tablet, a dry syrup agent, a liquid agent, or a jelly agent.
Item 3.
(A) One or more types selected from the group consisting of methylephedrine and its salts, and (B) one or more types selected from the group consisting of pseudoephedrine and its salts, (C) containing mequitazine Characterized by
The method to suppress the bitterness of the said internal use composition.

  In the internal use composition of the present invention, there is bitterness caused by (A) one or more selected from the group consisting of methylephedrine and a salt thereof, and (B) one or more selected from the group consisting of pseudoephedrine and a salt thereof. It is suppressed.

[Internal composition]
The internal use composition of the present invention,
(A) 1 or more types selected from the group which consists of methylephedrine and its salt (B) 1 or more types selected from the group which consists of pseudoephedrine and its salt, and (C) mequitazine.

  As described above, one or more selected from the group consisting of methylephedrine and a salt thereof used in the present invention (sometimes referred to as component (A) in this specification) have an action similar to that of ephedrine. It is a known compound that has a mechanism, that is, α action and β action, and is known to have bronchodilator action and central antitussive action. Obtained in a commercial product or according to a known method Can be manufactured.

  The salt of methylephedrine is not particularly limited as long as it is a pharmaceutically acceptable salt. For example, hydrochloride, hydrobromide, nitrate, sulfate, phosphate, oxalate, maleate, fumarate An acid salt etc. can be mentioned, and hydrochloride is preferable among them.

  When the internal composition is a solid preparation, the content of the component (A) in the internal composition of the present invention is preferably 0.1 to 50 w / w%, more preferably 0.1 to 40 w / w%, and further Preferably when the internal composition is a liquid or semi-solid preparation, it is preferably 0.01 to 30 w / w%, more preferably 0.05 to 20 w / w%, still more preferably 0. It is in the range of 05-10 w / w%. “Content of component (A)” means the total content when component (A) is a combination of two or more substances.

  One or more selected from the group consisting of pseudoephedrine and a salt thereof used in the present invention (sometimes referred to as component (B) in the present specification) are diastereomers of ephedrine as described above. Yes, it is a known compound that has a vasoconstrictive action by sympathetic α action and is known to suppress redness and swelling of the nasal mucosa, and is obtained as a commercial product or manufactured according to a known method Can do.

  The salt of pseudoephedrine is not particularly limited as long as it is a pharmaceutically acceptable salt. For example, hydrochloride, hydrobromide, nitrate, sulfate, phosphate, oxalate, maleate, fumaric acid A salt etc. can be mentioned, and hydrochloride is especially preferable.

  When the internal composition is a solid preparation, the content of the component (B) in the internal composition of the present invention is preferably 0.1 to 50 w / w%, more preferably 1 to 40 w / w%, still more preferably. 1-30 w / w%, When the internal use composition is a liquid or semi-solid preparation, it is preferably 0.01-40 w / w%, more preferably 0.1-30 w / w%, still more preferably 0.1 It is in the range of 20 w / w%. “Content of component (B)” means the total content when component (B) is a combination of two or more substances.

  The content ratio of the component (B) to 1 part by weight of the component (A) in the internal use composition of the present invention is preferably 0.01 to 30 parts by weight, more preferably 0.1 to 20 parts by weight, and still more preferably 0. It is in the range of 1 to 10 parts by weight.

  Mequitazine used in the present invention (which may be described as component (C) in the present specification) binds to the H1 receptor and inhibits histamine from binding to the H1 receptor, thereby providing an antiallergic action. Is a known compound (antihistamine compound) that can be obtained as a commercially available product or can be produced according to a known method.

  Mequitazine is usually free.

  When the internal composition is a solid preparation, the content of the component (C) in the internal composition of the present invention is preferably 0.01 to 30 w / w%, more preferably 0.1 to 20 w / w%, and further Preferably, 0.1-10 w / w%, when the internal composition is a liquid or semi-solid, preferably 0.001-10 w / w%, more preferably 0.01-5 w / w%, still more preferably It is in the range of 0.01-1 w / w%.

  The content ratio of the component (C) to 1 part by weight of the component (A) in the internal use composition of the present invention is preferably 0.001 to 10 parts by weight, more preferably 0.01 to 5 parts by weight, and still more preferably 0. Within the range of 0.01 to 0.5 parts by weight.

  The content ratio of the component (C) to 1 part by weight of the component (B) in the internal use composition of the present invention is preferably 0.001 to 10 parts by weight, more preferably 0.01 to 5 parts by weight, and still more preferably 0. Within the range of 0.01 to 0.5 parts by weight.

  The internal use composition of the present invention may contain other physiologically active ingredients as long as the effects of the present invention are sufficiently exerted.

Such components include, for example, antihistamine components (e.g., isothipentyl hydrochloride, iproheptin hydrochloride, dipheterol hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, triprolyzine hydrochloride hydrate, tripelenamine hydrochloride, tondilamine hydrochloride, Promethazine hydrochloride, methodirazine hydrochloride, diphenhydramine salicylate, carbinoxamine diphenyldisulfonate, alimemazine tartrate, diphenhydramine tannate, diphenylpyraline theoclurate, carbinoxamine maleate, chlorpheniramine maleate, promethazine methylenedi Salicylate),
Parasympathetic nerve blocking components (for example, atropine, scopolamine, belladonna total alkaloids, belladonna extract, iodopropamide iodide, datsura extract, funnel extract, etc.),
Other sympathomimetic components other than methylephedrine and pseudoephedrine (eg phenylephrine, phenylpropanolamine, ephedrine, ethylephrine, methoxamine, middolin, methoxyphenamine, etc.),
Anti-inflammatory enzymes (eg lysozyme, serrapeptase, bromelain, pronase, etc.),
Herbal medicine and herbal medicine-derived components (e.g., shrimp, licorice, carrot, mao, keihi, kei-gai, saishin, shin-i, nantenjitsu, baboon, beak, zenko, kyoto, shazenshi, gooh, gadju, peony, sojutsu, gentian, fennel, Onji, Awaku, Auren, Chikutsujinjin, Chimpi, Clove, Senega, Shazenso, Shajin, Glycyrrhizic acid, etc.),
Xanthine derivatives (for example, caffeine, theophylline, aminophylline, theobromine, diprofeline, proxyphylline, pentoxifylline, etc.),
Antipyretic analgesic ingredients (eg, aspirin, aspirin aluminum, acetaminophen, etenzamide, sazapyrine, salicylamide, sodium salicylate, lactylphenetidine, ibuprofen, ketoprofen, thiaramide, aluminoprofen, loxoprofen, etc.)
Antitussive ingredients (eg, achloramide, cloperastine, pentoxyberine (Carbetapentane), tipepidine, dibutate, dextromethorphan, codeine, dihydrocodeine, noscapine, etc.),
Expectorants (eg, potassium guaiacol sulfonate, guaifenesin, etc.),
Vitamins (eg, vitamins A [eg, retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene, etc.), vitamins B [eg, thiamine, thiamine disulfide, dicetiamine, octothiamine, chicotiamine, bisibutiamine, bis Benchamine, prosultiamine, benfotiamine, fursultiamine, riboflavin, flavin adenine dinucleotide, pyridoxine, pyridoxal, hydroxocobalamin, cyanocobalamin, methylcobalamin, deoxyadenocobalamin, folate, tetrahydrofolate, dihydrofolate, nicotinic acid, nicotine Acid amide, nicotinyl alcohol, pantothenic acid, panthenol, biotin, choline, inositol, etc.], vitamin C [for example, ascorbic acid, ethanol Sorbic acid, or derivatives thereof], vitamin Ds [for example, ergocalciferol, cholecalciferol, hydroxycholecalciferol, dihydroxycholecalciferol, dihydrotaxelol, etc.], vitamin E [eg, tocopherol and its derivatives, Ubiquinone derivatives, etc.], other vitamins [eg, hesperidin, carnitine, ferulic acid, γ-oryzanol, orotic acid, rutin, eriocitrin, etc.], and mucosal protective components (eg, aminoacetic acid, dry aluminum hydroxide gel) , Aluminum-based mucosal protective agent such as dihydroxyaluminum / aminoacetate; magnesium metasilicate magnesium aluminate, aluminum silicate, hydrotalcite, magnesium alumina hydroxide, aluminum hydroxide gel, aluminum hydroxide Ni-sodium hydrogen carbonate coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / calcium carbonate / magnesium carbonate coprecipitation product, magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium silicate, Magnesium-based mucosal protective agents such as coprecipitation products of magnesium hydroxide and potassium aluminum sulfate)
Etc.

  Among these, one or more selected from diphenylpyrine, iodopropamide, chlorpheniramine, glycyrrhizic acid, belladonna total alkaloids, caffeine, and salts thereof are preferable.

The internal use composition of the present invention is not limited to the above-mentioned components and any other components that can be usually used in pharmaceuticals, depending on the use or formulation form, etc., as long as the effects or formulation stability of the present invention are not impaired. May be contained as appropriate. Such a component is not particularly limited, and examples thereof include a carrier component or an additive.
For example, carrier components or additives in solid preparations include excipients, disintegrants, binders, lubricants, antioxidants, coating agents, colorants, surfactants, plasticizers, sweeteners, flavoring agents, Examples include flavoring agents, disintegration aids, foaming agents, adsorbents, preservatives, wetting agents, and antistatic agents.
In addition, for example, as a carrier component or additive in a liquid agent, a solvent, a pH adjuster, a cooling agent, a suspending agent, an antifoaming agent, a thickening agent, a solubilizing agent, a surfactant, an antioxidant, a coloring agent Agent, sweetener, flavoring agent, antiseptic / antibacterial agent, chelating agent, solubilizer, solubilizer, stabilizer, fluidizer, emulsifier, thickener, buffer, isotonic agent, and dispersant Etc.
Here, since the bitterness is suppressed in the internal use composition of this invention, the usage-amount of the sweetener and the corrigent which aim at suppression of a bitterness can be reduced.

  Although the component which the internal use composition of this invention may contain below is specifically illustrated, it is not limited to these components.

  Excipients: sugar alcohol (eg, D-sorbitol, D-mannitol, xylitol), sugar (eg, glucose, sucrose, lactose, fructose), crystalline cellulose, carmellose sodium, croscarmellose sodium, calcium hydrogen phosphate, Wheat starch, rice starch, corn starch, potato starch, dextrin, β-cyclodextrin, light anhydrous silicic acid, titanium oxide, magnesium aluminate metasilicate, talc, kaolin, etc.

  Disintegrants: low-substituted hydroxypropylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, hydroxypropyl starch, partially pregelatinized starch and the like.

  Binder: Cellulose derivatives (eg, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose), polyvinylpyrrolidone, polyvinyl alcohol, acrylic polymer, gelatin, gum arabic, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate , Propylene glycol alginate and the like.

  Lubricants: stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax, beeswax, etc.

  Antioxidants: Dibutylhydroxytoluene (BHT), propyl gallate, butylhydroxyanisole (BHA), tocopherol, citric acid and the like.

  Coating agent: Hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate phthalate, polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer, methacrylic acid Copolymer, shellac, etc.

  Colorant: Food Red No. 2, Food Red No. 3, Food Red No. 102, Food Yellow No. 4, Food Yellow No. 5, Food Blue No. 1, Food Yellow No. 4, Metal Lake, Copper Chlorofin Sodium, Riboflavin, Turmeric Extract Carotene solution etc.

  Surfactant: Polyoxyethylene hydrogenated castor oil, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, polyoxyethylene polyoxypropylene, polysorbates, sodium lauryl sulfate, macrogol, sucrose fatty acid ester, and the like.

  Plasticizer: triethyl citrate, polyethylene glycol, triacetin, cetanol and the like.

  Sweetener: Natural or synthetic sweetener (eg, sucrose, mannitol, aspartame).

  Flavoring agents: aspartame, ascorbic acid, stevia, menthol, licorice crude extract, simple syrup, etc.

  Flavoring agents: menthol, camphor, borneol, cinnamaldehyde, etc.

  Solvent: water, ethanol, isopropanol, lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, behenyl alcohol, 2-hexyl decanol, isostearyl alcohol, 2-octyldodecanol and the like.

  pH adjuster: citric acid, malic acid, sodium hydrogen phosphate, dipotassium phosphate, etc.

  Cooling agents: l-menthol, mint water, etc.

  Suspending agents: kaolin, carmellose sodium, xanthan gum, methylcellulose, tragacanth, etc.

  Antifoaming agent: dimethylpolysiloxane, silicon antifoaming agent, etc.

  Thickener: xanthan gum, tragacanth, methylcellulose, dextrin, etc.

  Solubilizer: ethanol, sucrose fatty acid ester, macrogol, etc.

The internal use composition of the present invention is, for example, a pharmaceutical, a quasi-drug, a food, or a raw material thereof [for example, a pharmaceutical preparation, a quasi-drug preparation, a food for specified health use, a nutritional functional food, a food for the elderly, a special use Food, functional food, health supplement (supplement), food preparation (eg, confectionery tablet)].
The preparation form of the internal use composition of the present invention is not particularly limited as long as internal use is possible. Specific examples of such dosage forms include powders, powders, fine granules, granules, pills, capsules, tablets [plain tablets, sugar-coated tablets, intraoral quick disintegrating tablets, chewable tablets (chewable tablets) , Effervescent tablets, troches, film-coated tablets, etc.], dry syrups, liquids [including suspensions, emulsions, syrups, limonades, etc.], jelly agents, and confectionery agents [candy (candy), gummi , Including nougat agents and the like].

  When the internal use composition of this invention is a liquid agent or a jelly agent, 2-8 are preferable, as for the pH (25 degreeC) of an internal use composition, 2.5-7 are more preferable, and 3-6 are still more preferable.

  The internal use composition of this invention can be manufactured by employ | adopting the normal formulation method according to the formulation form. For example, the above-mentioned components can be granulated (eg, extrusion granulation, fluidized bed granulation, spray drying granulation, etc.), dried, and sieved to produce granules. Using this, capsules or tablets can be produced by a conventional method. Also, for example, after each component is dissolved in an appropriate amount of purified water, the pH is preferably adjusted to 2-8, more preferably 2.5-7, still more preferably 3-6, and then the remaining purification. It can be produced by adjusting the volume by adding water. Here, it is preferable to employ a method in which the component (A), the component (B), and the component (C) are sufficiently mixed.

The internal use composition of this invention can also be filtered and sterilized as needed, and can also be filled with a container. The container for filling may be any material using a material that can be used for a general container in the field, such as a plastic material, a glass material, and a metal material. It can be selected and used.
When the internal use composition of this invention is a liquid agent or a jelly agent, the packaging form may be a single-off type packaging form, and is a multi-dose packaging form that is continuously taken multiple times. There may be.

  The internal use composition of the present invention is used for the treatment of any disease for which (A) methylephedrine or a salt thereof, (B) pseudoephedrine or a salt thereof, (C) mequitazine, or a combination thereof is desired. For example, it can be used for applications such as bronchodilation, improvement of nasal congestion, suppression of nasal secretion. The internal use composition of this invention can be administered by the method similar to a normal internal use composition.

The dosage of the internal composition of the present invention is appropriately set depending on the form, administration method, administration purpose, and age, weight, and symptoms of the administration subject of the composition, and is not constant. Further, the internal composition of the present invention may be administered once or divided into several times within a desired dose range, and administered before meals, between meals, after meals, or at the same time as meals. May be. In addition, the term “administration” in the present specification is intended to include “taking”. The term “internal use” in this specification may be used interchangeably with “oral administration”.
The internal use composition of the present invention contains (A) one or more selected from the group consisting of methylephedrine and a salt thereof, and (B) one or more selected from the group consisting of pseudoephedrine and a salt thereof. The bitterness derived from these has the outstanding effect that it is suppressed. Therefore, the present invention also includes (A) one or more types selected from the group consisting of methylephedrine and a salt thereof, and (B) one or more types selected from the group consisting of pseudoephedrine and a salt thereof. The present invention also provides a method for suppressing bitterness.
Specifically, the method for suppressing the bitterness of the internal use composition includes: (A) one or more selected from the group consisting of methylephedrine and a salt thereof; and (B) pseudoephedrine and a salt thereof. If (C) mequitazine is contained together with 1 or more types selected from the group which consists of, there will be no limitation in particular.
In addition, the method for inhibiting bitterness of the present invention is a method of formulating by adding a sweetening agent or a corrigent to a component having bitterness, a method of formulating by coating the component having bitterness with sugar coating, or encapsulating in a capsule It can also be used in combination with other methods of inhibiting bitterness, such as a method of formulating.
In the method for suppressing bitterness of the internal use composition, the mixing of the component (A), the component (B) and the component (C) may be simultaneous or sequential, and the order thereof is not particularly limited. In addition, in these methods, the types of components (A), (B) and (C) to be used, their contents, and their proportions, the types of other components used, preparation methods, and uses The preparation form, administration subject, and the like are the same as those of the internal use composition of the present invention.

  EXAMPLES Hereinafter, although this invention is demonstrated based on an Example, this invention is not limited at all by these Examples.

Test example 1
The internal compositions of Comparative Example 1 and Example 1 shown in Table 1 were prepared, and bitterness was evaluated using these internal compositions in accordance with the visual analog scale (VAS). Specifically, each component shown in Table 1 was weighed and then mixed in a mortar to obtain a uniform internal composition. A predetermined amount of each internal composition was weighed to prepare a sample for sensory test. Each panelist included a sensory test sample in the mouth and compared the bitterness. Each sample was included in the mouth, and after bitterness was evaluated, the mouth was swallowed with distilled water, and all were discharged. The panelists felt on the subjective symptom survey sheet that each sample was included in the mouth and “bitter” felt immediately after that was 0 cm when “bitter” was not felt, 5 cm when it was felt, and 10 cm when it was felt strongly. The length (cm) was calculated as a bitter score, describing the degree of “bitter”. In addition, as a panelist, the bitter score of the comparative example 1 was selected 5 or more. In addition, the bitter scores of Comparative Examples 1 and 2 were compared, and the “X” mark was written on the higher bitter score. In this case, if there is no difference between the two, neither of them is marked with an “X” mark.
dl-Methylephedrine hydrochloride, mequitazine, and lactose conform to the 16th revised Japanese Pharmacopoeia standard, and pseudoephedrine hydrochloride conforms to the standard of pseudoephedrine hydrochloride of the Japanese Pharmacopoeia Standard 2002. Moreover, the unit of component content in Table 1 is mg.

Bitterness of an oral composition (Comparative Example 1) containing dl-methylephedrine hydrochloride and pseudoephedrine hydrochloride, and an internal composition (Example 1) containing mequitazine together with dl-methylephedrine hydrochloride and pseudoephedrine hydrochloride When comparing bitterness, all three panelists rated Comparative Example 1 as being more bitter.
Therefore, by including mequitazine in the oral composition containing dl-methylephedrine hydrochloride and pseudoephedrine hydrochloride, the bitterness of the oral composition containing dl-methylephedrine hydrochloride and pseudoephedrine hydrochloride is suppressed. It became clear.

Test example 2
The internal use compositions of Comparative Examples 2 to 4 and Example 2 shown in Tables 2 to 4 were prepared, and the bitterness of the internal use composition was evaluated in the same manner as in Test Example 1.
In addition, dl-methylephedrine hydrochloride, mequitazine and lactose comply with the 16th revised Japanese Pharmacopoeia standard, and pseudoephedrine hydrochloride conforms to the standard of pseudoephedrine hydrochloride of the Japanese Pharmacopoeia Standard 2002. . Moreover, the unit of component content in Tables 2-4 is mg.

The evaluation of all the panelists agreed, and the bitterness of the internal composition containing dl-methylephedrine hydrochloride (Comparative Example 2) and the internal composition containing mequitazine together with dl-methylephedrine hydrochloride (Comparative Example 3) There was no difference in bitterness, and bitterness was not reduced even when mequitazine was added to an oral composition containing dl-methylephedrine hydrochloride but not pseudoephedrine hydrochloride.
Moreover, the bitterness of the internal use composition (Comparative Example 2) containing dl-methylephedrine hydrochloride is compared with the bitterness of the internal use composition (Comparative Example 4) containing pseudoephedrine hydrochloride together with dl-methylephedrine hydrochloride. Then, the bitterness of the internal use composition was reinforced by making the internal use composition containing dl-methyl ephedrine hydrochloride contain the pseudoephedrine hydrochloride more strongly in the comparative example 4.
On the other hand, the bitterness of the internal use composition (Comparative Example 4) containing dl-methylephedrine hydrochloride and pseudoephedrine hydrochloride, and the internal use composition containing mequitazine together with dl-methylephedrine hydrochloride and pseudoephedrine hydrochloride ( When compared with the bitterness of Example 2), the bitterness of Comparative Example 4 was stronger, and the bitterness of the internal use composition was suppressed by containing mequitazine.
Similar to Test Example 1, the oral composition containing dl-methylephedrine hydrochloride and pseudoephedrine hydrochloride has mequitadine so that the oral composition contains dl-methylephedrine hydrochloride and pseudoephedrine hydrochloride. It was shown that bitterness was suppressed.

Test example 3
The internal compositions of Comparative Examples 5 to 6 and Examples 3 to 4 shown in Tables 5 to 6 were prepared, and the bitterness of the internal compositions was evaluated in the same manner as in Test Example 1.
In addition, dl-methylephedrine hydrochloride, mequitazine and lactose comply with the 16th revised Japanese Pharmacopoeia standard, and pseudoephedrine hydrochloride conforms to the standard of pseudoephedrine hydrochloride of the Japanese Pharmacopoeia Standard 2002. . Moreover, the unit of component content in Tables 5-6 is mg.

Bitterness of oral compositions containing dl-methylephedrine hydrochloride and pseudoephedrine hydrochloride (Comparative Examples 5 to 6), and oral compositions containing mequitazine together with dl-methylephedrine hydrochloride and pseudoephedrine hydrochloride (Example 3) When compared with the bitterness of ~ 4), the bitterness of Comparative Examples 5-6 was stronger, and the bitterness of the internal use composition was suppressed by containing mequitazine.
Therefore, even if the concentration of dl-methylephedrine hydrochloride is different, dl-methylephedrine hydrochloride and pseudoephedrine hydrochloride containing mequitazine can be added to the oral composition containing dl-methylephedrine hydrochloride and pseudoephedrine hydrochloride as in Test Examples 1 and 2. -It was shown that the bitterness which the internal-composition composition containing a methylephedrine hydrochloride and a pseudoephedrine hydrochloride has was suppressed.

Tablets (Examples 5 to 16) having the compositions shown in Tables 7 to 8 were prepared by a conventional method.
Unit: parts by weight

Unit: parts by weight

Powders (Examples 17 to 28) having the compositions shown in Tables 9 to 10 were prepared by a conventional method.
In addition, the powder of Examples 17-28 can also be dissolved and drunk in water.
Unit: parts by weight

Unit: parts by weight

  The liquid agent (Examples 29-40) which has a composition shown to Tables 11-12 was prepared by the conventional method.

Unit: parts by weight

Unit: parts by weight

Claims (3)

(A) One or more types selected from the group consisting of methylephedrine and its salts (B) One or more types selected from the group consisting of pseudoephedrine and its salts, and (C) an internal use composition containing mequitazine. The internal use composition of Claim 1 which is a powder, a fine granule, a granule, an uncoated tablet, a dry syrup agent, a liquid agent, or a jelly agent. (A) One or more types selected from the group consisting of methylephedrine and its salts, and (B) one or more types selected from the group consisting of pseudoephedrine and its salts, (C) containing mequitazine Characterized by
The method to suppress the bitterness of the said internal use composition.