JP2003171314A - Oral administration solution composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a readily drinkable oral administration solution composition having an improved flavor by suppressing a strong bitter taste, a peculiar bitter taste, or the like. <P>SOLUTION: This oral administration solution composition comprises 0.5-35 mg/ml of at least any of an organic acid and an alkali metal salt of the organic acid, a physiologically active ingredient having the bitterness, a sweetener and a fruity perfume, and has pH at 3.5-6.0. A mode, and the like, in which the sweetener is at least one kind selected from sucrose, fructose, glucose, lactose, a reducing maltose syrup, a powder reducing maltose syrup, a glucose fructose liquid sugar, a fructose glucose liquid sugar, honey, sorbitol, maltitol, mannitol, xylitol, erythritol, aspartame, saccharin and saccharin sodium are preferred as the sweetener. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an internal liquid preparation composition in which the bitterness of a physiologically active ingredient is reduced and the flavor is improved.

[0002]

2. Description of the Related Art Many oral liquid preparations have been developed and put into practical use because they are easy to take. However, many effective physiologically active substances have an intense bitterness or a peculiar bitterness, and in many cases, a strong bitterness is exhibited even if they are mixed in a small amount in a liquid preparation. In such a case, there is a problem in that it causes pain during administration, and the advantage of the oral liquid preparation, such as ease of administration, is impaired. In addition, there is a problem that it is difficult for children to take.

[0003] In order to solve such a problem, a device for masking bitterness has been conventionally devised, and generally, a sweetener, a sour agent, a flavoring agent, a flavoring agent and the like are blended to mask the bitterness and the peculiar odor. The method has been adopted. However, depending on the bitterness component, a satisfactory flavor cannot be produced,
If the degree of bitterness is extremely strong or the quality of bitterness is specific and it is difficult to take it, there is a limit to improving the ease of taking just by mixing the conventionally proposed sweetener and sour agent. there were. In particular, when the liquid medicine for internal use is a drug, there is a problem that the amount of the compound is limited from the viewpoint of safety and the flavoring agent causes a decrease in stability of the medicinal component. Further, there is a problem that the stability of the flavoring agent itself is impaired and the masking effect is diminished, and further measures have been demanded.

[0004]

SUMMARY OF THE INVENTION It is an object of the present invention to solve the various problems in the prior art and achieve the following objects. That is, an object of the present invention is to provide an internal-use liquid agent composition in which the flavor is improved by suppressing strong bitterness or specific bitterness and the like and which can be easily taken.

[0005]

Means for solving the above-mentioned problems are as follows. That is, <1> 0.5 to 35 mg / ml of at least one of an organic acid and an alkali metal salt of an organic acid, a physiologically active ingredient having a bitterness, a sweetener, and a fruit-based flavor, and a pH of It is the internal-use liquid agent composition characterized by being 3.5-6.0. <2> Sweeteners are sucrose, fructose, glucose, lactose, reduced maltose syrup, powdered reduced maltose syrup, glucose-fructose syrup, fructose glucose syrup, honey, sorbitol, maltitol, mannitol, xylitol, erythritol, <1 which is at least one selected from aspartame, saccharin, and saccharin sodium
The oral solution composition described in

<3> Organic acids include citric acid, malic acid,
<1> or <2>, which is at least one selected from lactic acid, tartaric acid, and benzoic acid, wherein the alkali metal salt of an organic acid is at least one selected from the alkali metal salts of each organic acid. The oral solution composition described in 1. <4> Fruit flavors are orange, strawberry,
Raspberry, peach, grape, passion fruit,
Mandarin, melon, apple, pineapple, and
<1>, which is at least one kind selected from cherry
To <3>.

<5> Fruit-based flavoring ingredients include limonene, linalool, citral, decanal, ethyl butyrate, γ-undecalactone, terpineol, allyl hexanoate, butyl acetate, butyl butyrate, isoamyl acetate, maltol, The oral liquid composition according to any one of <1> to <4>, which is at least one selected from ethyl lactate, γ-decalactone, and cis-3-hexanol. <6> The above <1> to <5> containing a polyhydric alcohol
The oral liquid composition according to any one of 1.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below.
The oral solution composition of the present invention contains at least one of an organic acid and an alkali metal salt of an organic acid, a physiologically active ingredient, a sweetener, and a fruit-based flavor, and optionally contains other ingredients. .

[Physiologically active ingredient] The physiologically active ingredient is a physiologically active ingredient having a bitter taste, and has a bitterness such as a cold remedy, an antipyretic agent, an analgesic, an antiphlogistic, an antitussive, an expectorant, an antihistamine or a hemostatic. Ingredients; crude drugs; B vitamins; and food additives; and the like. They are,
They may be used alone or in combination of two or more.

Specific examples of the physiologically active ingredient include:
Acetaminophen, aspirin, phenacetin, mefenamic acid, antipyrine, phenylbutazone, sulpiline, diclofenac sodium, ibuprofen, ketoprofen, naproxen, epirizole, tiaramid hydrochloride, indomethacin, pentazocine, acetylcholine chloride, alimemazine tartrate hydrochloride, cyproheptadine, diphenhydramine hydrochloride, diphenhydramine hydrochloride. , Chlorpheniramine maleate, codeine phosphate, dihydrocodeine phosphate, dextromethorphan hydrobromide, pentoxyberine citrate, theophylline, aminophylline, ephedrine hydrochloride, epinephrine hydrochloride, salbutamol sulfate, trimethoquinol hydrochloride, procaterol hydrochloride, Methylephedrine hydrochloride, phenylpropanolamine hydrochloride, guaife Singh, tranexamic acid, anhydride caffeine, and caffeine and the like. These may be used alone or in combination of two or more.

Further, the herbal medicines include aloe, fennel, turmeric, oyster, sago, ages, ougi,
Dwarf, Onji, Guarana, Beetle, Giou, Touki,
Eucommia, carrot, amarogentin, swordfish, slug, sardine, zedoary, cascara sagrada, cuckoo, cascari tree, sorghum grass, crow conger, cypress, pearl oyster, kyounin, kihada, wolfberry, cucumber, cabbage, ginkgo, ginkgo, ginkgo, gentian , Kojin, kobushi, koboku, kohoku, goshitsu, goshuyu, goshi, colombo, konzulango, psycho, sanshishi, saffron, sandscone, dio, shikon, perilla, peony, shajin (genus ginseng), shazen (plantain), jascent, ginger, ginger. , Ginger, seihi, bakushokon, senkyu, senkoutsu, centaurium grass, senburi, senbou, senso, senna, sojutsu, sokuhaku, soyo, rhubarb, ginseng bamboo shoots, chimo Chiretta grass, citrus unshiu peel,
Spruce, tounin, turmeric, bittern, carrot, juniper, juniper, belladonnacon, henoposite oil,
Yakuchi, yutan, mugwort, mugwort, bitter tincture,
Jisyu, hop, homika, bowie, maoh, mokutsu, mokko, ryutan, gentian, luzonka, forsythia, carrot, senega, kyokyou, ginkgo,
Further, royal jelly and the like can be mentioned, and all the herbal medicines described in the pharmaceutical manufacturing guidelines can be mentioned. These may be used alone or in combination of two or more.

As the vitamin B group, vitamin B
1 group (eg thiamine, thiamine nitrate, thiamine hydrochloride,
Vitamin B1 derivative), vitamin B2 group (eg riboflavin, sodium riboflavin phosphate, riboflavin butyrate riboflavin, etc.), vitamin B6 group (eg pyridoxine, pyridoxal, pyridoxamine and phosphoric acid or hydrochloride thereof), vitamin B12 group (eg cobalamin,
Cyanocobalamin, methylcobalamin, etc.) and the like. These may be used alone or in combination of two or more. When these ingredients having bitterness are used as active ingredients, it is preferable to add them in an effective amount range that produces a medicinal effect according to their respective purposes. Also,
Food additives include vitamin B ₁₂ , folic acid, calcium pantothenate, potassium chloride, starch husk powder, niacinamide, biotin, seaweed powder, nicotinic acid amide, and
Cyanocobalamin and the like can be mentioned. These may be used alone or in combination of two or more.

[Sweetener] Examples of the sweetener include:
Sucrose, fructose, glucose, lactose, reduced maltose syrup, powdered reduced maltose syrup, glucose fructose syrup, fructose glucose syrup, honey, sorbitol, maltitol, mannitol, xylitol, erythritol, aspartame, saccharin, and saccharin sodium. It is preferable to contain at least one selected from the group consisting of sucrose, fructose, powdered reduced maltose starch syrup, xylitol, and more than one selected from erythritol. Therefore, it is particularly preferable that sucrose is contained, and the content of reducing sugar is 0.05.
It is most preferable that the content of sucrose is less than 100% because the flavor is particularly improved.

[Organic Acids, Alkali Metal Salts of Organic Acids] The organic acids include citric acid, malic acid, lactic acid, tartaric acid,
And benzoic acid and the like. These may be used alone or in combination of two or more. Examples of the alkali metal salt of the organic acid include all the alkali metal salts of the organic acids specifically mentioned as the organic acid.
These may be used alone or in combination of two or more.

The content of at least one of the organic acid and the alkali metal salt of the organic acid in the oral solution composition must be 0.5 to 35 mg / ml, and 2 to 20 mg / ml. Is more preferred, and 5 to 1
More preferably 5 mg / ml. The content is 0.5 m
If it is less than g / ml, the buffering capacity will be weakened and the flavor will be poor, while if it exceeds 35 mg / ml, it will make you thirsty.
The usability deteriorates. When the organic acid and the organic acid salt are used in combination, the compounding ratio (molar ratio: organic acid / organic acid salt) is 1/10 to 10 in that the taste in the internal liquid preparation composition is particularly good. / 1 is preferable, and 1/5 to 5/1 is more preferable.

[Fruit-based fragrance] Examples of the fruit-based fragrance include orange flavor, strawberry,
Examples include raspberries, cranberries, peaches, grapes, passion fruits, grapefruits, pineapples, limes, lemons, mandarins, melons, apples, cherries, plums, and various fruit flavors such as apricots. These may be used alone or in combination of two or more. Among these, orange, strawberry, peach, raspberry, pineapple, cherry, and passion fruit are particularly preferable in that the improvement of flavor is suitable.

Examples of the component of the fruit-based flavoring agent include limonene, linalool, citral, decanal,
Ethyl butyrate, γ-undecalactone, terpineol, allyl hexanoate, butyl acetate, butyl butyrate, isoamyl acetate, maltol, ethyl lactate, γ-decalactone, and cis-3
-Hexanol and the like have a high bitterness masking effect, and are preferably cited. These may be used alone or in combination of two or more.

[Other Ingredients] As the above-mentioned other ingredients, in addition to pH adjusters, polyhydric alcohols, etc., other active ingredients generally used in oral liquid preparations, flavoring agents, preservatives, preservatives, and flavoring agents. , Fragrance, cooling agent, surfactant, solubilizer, emulsifier, solvent, buffer, suspension agent, thickener, colorant,
Stabilizers, solubilizing agents and the like can be mentioned. These may be used alone or in combination of two or more.

The pH adjusting agent can be appropriately used for the purpose of adjusting the pH of the oral solution composition of the present invention to 3.5 to 6.0. As the pH adjuster,
For example, inorganic modifiers such as sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, hydrochloric acid, sulfuric acid, and phosphoric acid, and organic substances such as citric acid, tartaric acid, malic acid, lactic acid, acetic acid, and salts thereof. Examples thereof include acid-based pH adjusters.

It is preferable that the polyhydric alcohol is contained so that the flavor of the fruit flavor is improved. Examples of the polyhydric alcohol include polyhydric alcohols other than the monosaccharides and disaccharides described in the above "sweetener", for example, water-soluble cellulose such as glycerin, propylene glycol, polyethylene glycol, polyvinyl alcohol and hydroxypropyl cellulose. Is mentioned. Among these, glycerin is most preferable because it has particularly good stability and flavor. The content of the polyhydric alcohol in the oral solution composition is preferably 0.1 to 30% by mass, more preferably 0.5 to 20%.

Examples of other active ingredients which are generally added to the oral liquid preparations include, for example, tipepidine hibenzate, bromhexine hydrochloride, lysozyme chloride, vitamin preparations (vitamin A group, vitamin D group, vitamin E group, nicotinic acid amide, etc.). ), Other active ingredients (sodium chondroitin sulfate, taurine, etc.) and the like.

Examples of the corrigent include fruit juice and the like. Examples of the preservatives and preservatives include sodium sorbate, benzoic acids (benzoic acid, sodium benzoate, etc.), parabens (ethyl paraoxybenzoate, butyl paraoxybenzoate, propyl paraoxybenzoate, etc.) and the like. Can be mentioned.

Examples of the surfactants, solubilizers, emulsifiers, and solvents include nonionic surfactants such as sucrose fatty acid esters, polyoxyethylene hydrogenated castor oils, polysorbates and pluronics, and ethanol. , Distilled water for injection, purified water and the like. Examples of the suspending agent and viscous agent include gum arabic, crystalline cellulose, bee gum, xanthan gum, gelatin, metrose and edible salts thereof, carmellose and edible salts thereof, and the like. Examples of the colorant include caramel, β-carotene, and various food colors (food yellow 1
No., edible red No. 2, etc.) and the like. Examples of the stabilizer include an edible salt of edetic acid, sodium chloride, and an edible salt of pyrosulfite.

These other ingredients (other active ingredients which are generally mixed in oral solutions, flavoring agents, preservatives, preservatives, flavoring agents, aromatic agents, cooling agents, surfactants, solubilizing agents, emulsifiers) , Solvent, pH adjusting agent, buffering agent, suspending agent, thickening agent, coloring agent, stabilizing agent, solubilizing agent, etc.) in the oral solution composition is not particularly limited, It is preferably contained in an amount suitable for the oral liquid preparation.

<Liquidity (pH) of Oral Solution Composition> The pH of the orally administered liquid composition of the present invention is 3.5 to
6.0 is preferable, 3.8 to 6.0 is more preferable,
More preferably, it is 4.0 to 5.5. By setting the pH of the above-mentioned oral liquid composition within the above numerical range, the bitterness can be effectively masked, and a good sweetness without habit can be obtained.

<Preparation Method of Oral Solution Composition> The preparation method of the oral solution composition of the present invention is not particularly limited, and all commonly used preparation methods are preferably exemplified. Usually, each component and a part of a solvent such as purified water are mixed and dissolved, and the remaining solvent is added to adjust the liquid amount. For example, the optimum pH of the formulation
Or to remove or solubilize insoluble matter,
The pH may be adjusted using an acid or an alkali, if necessary. Incidentally, when it contains a component which is hardly soluble in water or insoluble in water, it is suitable to use the above-mentioned surfactant, solubilizer, emulsifier,
Solubilization, emulsification, suspension and the like can be achieved by selecting a suspending agent and adding a generally used appropriate amount. If necessary, a solvent such as purified water may be heated at the time of dissolution according to a general method for preparing an oral solution. During the preparation, flavors may be added at the final stage of preparation so as not to impair the flavor. Each component is administered at a known dose depending on the active ingredient.

<Aspects of Use of Oral Solution Composition> There are no particular restrictions on the manner of use of the aforementioned oral fluid composition of the present invention, and known modes of use, such as drinks, syrups, extracts, elixirs, It can be used as a liquid medicine for internal use such as a limonade agent, a soft capsule, and a capsule capable of holding an aqueous content.

[0028]

EXAMPLES The present invention will be described in more detail with reference to examples and comparative examples, but the present invention is not limited to the following examples.

(Examples 1 to 21 and Comparative Examples 1 to 4) By the conventional method, the oral solution compositions having the compositions shown in Tables 1 to 5 were prepared, and a sensory test was carried out by 10 panelists.
Regarding bitterness and ease of drinking, according to the following evaluation criteria, 1 to
It was evaluated by a 5-point score evaluation of 5 points. The results are shown in Tables 1-5. Each composition in Tables 1 to 5 is represented by a numerical value in "mg" unit unless otherwise specified.

-Bitterness and ease of drinking- 5 points: Very easy to drink without bitterness 4 points: Almost no bitterness and easy to drink 3 points: Slightly bitter, difficult to drink 2 points: bitter, difficult to drink 1 point: very bitter, very difficult to drink

[0031]

[Table 1]

[0032]

[Table 2]

[0033]

[Table 3]

[0034]

[Table 4]

[0035]

[Table 5]

It should be noted that in Table 5, 1 of the Rhododendron extract
mL corresponds to 1000 mg in terms of the original drug, and 1 mL of Senega flow extract corresponds to 1000 mg in terms of the original drug.

Next, the "orange flavor" used in Examples 1 to 21 was mixed with strawberry, raspberry, cranberry, peach, grape, passion fruit, grapefruit, pineapple, lime, lemon, mandarin, melon, apple, cherry and plum. In addition to substituting the flavors of apricot, apricot, and limonene,
An oral solution composition was prepared in the same manner as in Examples 1 to 21,
When evaluated in the same manner as in Examples 1 to 21, good results were obtained in all cases.

[0038]

INDUSTRIAL APPLICABILITY According to the present invention, by suppressing strong bitterness, specific bitterness and the like, it is possible to provide an oral liquid composition which is improved in flavor and can be easily taken.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 47/14 A61K 47/14 47/16 47/16 47/22 47/22 47/26 47/26 ( 72) Inventor Yoshio Ogasawara 1-3-7, Honjo, Sumida-ku, Tokyo F-term in Lion Co., Ltd. (reference) 4C076 AA11 BB01 CC04 CC29 DD22 DD30 DD34 DD37 DD38 DD40 DD41 DD43 DD45 DD59 DD60 DD61 DD67 EE41 EE56 EE57 EE58 FF11 FF52

Claims (6)

[Claims] 1. An organic acid and / or an alkali metal salt of an organic acid is contained in an amount of 0.5 to 35 mg / ml, a physiologically active ingredient having a bitter taste, a sweetener, and a fruit-based flavor, and the pH is An oral solution composition, which is 3.5 to 6.0. 2. The sweetener is sucrose, fructose, glucose, lactose, reduced maltose syrup, powdered reduced maltose syrup, glucose fructose syrup, fructose glucose syrup, honey, sorbitol, maltitol, mannitol, xylitol, The oral solution composition according to claim 1, which is at least one selected from erythritol, aspartame, saccharin, and saccharin sodium. 3. The organic acid is citric acid, malic acid, lactic acid,
The oral liquid preparation according to claim 1 or 2, which is at least one selected from tartaric acid and benzoic acid, and the alkali metal salt of an organic acid is at least one selected from alkali metal salts of each of the organic acids. Composition. 4. The fruit-based flavoring agent is orange, strawberry, raspberry, peach, grape, passion fruit, mandarin, melon, apple, pineapple,
And at least one selected from cherries, The oral liquid composition according to any one of claims 1 to 3. 5. The fruit-based flavor component is limonene, linalool, citral, decanal, ethyl butyrate, γ-undecalactone, terpineol, allyl hexanoate, butyl acetate, butyl butyrate,
The oral solution composition according to any one of claims 1 to 4, which is at least one selected from isoamyl acetate, maltol, ethyl lactate, γ-decalactone, and cis-3-hexanol. 6. A polyhydric alcohol is contained in any one of claims 1 to 5.
The oral solution composition according to any one of 1.