JP2002114674A - Suspending agent for medicine containing branched-chain amino acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a readily administrable suspension preparation for a medicine by lowering the bitterness of a suspension preparation containing branched- chain amino acids having a strong bitterness as an active ingredient. SOLUTION: This suspending agent is characterized in that the suspending agent comprises three kinds of branched-chain amino acids composed of isoleucine, leucine and valine as active ingredients and at least one kind of an organic acid (citric acid, malic acid, tartaric acid, ascorbic acid, or the like), as an acidulant.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a suspension preparation which is easy to take and contains three kinds of branched-chain amino acids consisting of isoleucine, leucine and valine as active ingredients. In particular, the present invention relates to a suspension formulation containing, as an active ingredient, three types of branched chain amino acids consisting of strongly bitter isoleucine, leucine and valine, which alleviates the bitterness and makes it easy to take.

[0002]

2. Description of the Related Art Pharmaceutical preparations containing three types of branched-chain amino acids consisting of isoleucine, leucine and valine are effective therapeutic agents for cirrhosis, but currently commercially available preparations are mainly granules. In the case of a granular preparation containing the above three types of branched-chain amino acids, the single dose is about 5 g, which is significantly larger than that of a general preparation, and is difficult to take due to its strong bitterness. In general, the bitterness of pharmaceuticals can be masked by adding a sweetener such as sucrose, and when the bitterness is persistent, the masking effect is obtained by using a highly residual sweetener such as saccharin or glycyrrhizic acid in combination. Can be given.

[0003] On the other hand, a drug which is difficult to take due to a large dose at one time is also used as a suspending agent which does not require water at the time of taking and which can pass through the throat. However, in the case of a commercially available suspension preparation, the concentration of the main drug in the suspension is 10% or less, and ordinary suspension preparations such as a therapeutic drug for liver cirrhosis whose main drug is a branched-chain amino acid consisting of isoleucine, leucine and valine are used. In many cases, it is necessary to prepare a suspension formulation having a much higher concentration than a usual suspension formulation in order to take the required amount in a single dose.

[0004] In the case of a drug for treating cirrhosis whose main drug is isoleucine, leucine and valine, if the concentration is about 10% or more, which is close to the upper limit of the concentration of a normal suspension, the storage of the suspension may be shortened. The main drug precipitates in
Since the sediment eventually causes caking and becomes in a state of poor redispersibility, measures must be taken to prevent such caking and maintain redispersibility.
For the above reasons, it is difficult to prepare a preparation containing three types of branched-chain amino acids consisting of isoleucine, leucine and valine, which is strongly bitter and has a significantly large dose per dose, as a suspension preparation. A suspension formulation containing the three branched-chain amino acids as the main drug has not been developed.

[0005]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an isoleucine having reduced the bitterness of a branched-chain amino acid in a suspension preparation in which a single dose of a highly bitter branched-chain amino acid drug is appropriately administered as a pharmaceutical. , Leucine and valine.

[0006]

The present invention, which can achieve the above object, includes the following inventions. (1) A pharmaceutical suspension containing three types of branched-chain amino acids consisting of isoleucine, leucine and valine as an active ingredient, and at least one organic acid as a sour agent.

(2) contains, as an active ingredient, three kinds of branched-chain amino acids consisting of isoleucine, leucine and valine;
A pharmaceutical suspension preferably comprising at least one selected from citric acid, malic acid, tartaric acid, and ascorbic acid as an acidulant.

(3) a sweetener and / or menthol selected from the group consisting of saccharin sodium, glycyrrhizic acid, aspartame, mannitol and trehalose;
The pharmaceutical suspension according to the above (1) or (2), further comprising a flavoring agent comprising at least one of ethanol.

(4) The pH of the pharmaceutical suspension is from 2.5 to 6.0.
The pharmaceutical suspension according to any one of the above items (1) to (3), wherein

(5) The pharmaceutical suspension according to any one of items (1) to (4), wherein the particle size D50 of the isoleucine and leucine is 3 to 350 μm, particularly 50 to 350 μm. Agent.

(6) Isoleucine and leucine having a particle size D50 of 100 μm or less, particularly 3 to 50 μm, are provided with a coating selected from an enteric coating, a water-insoluble coating and a gastric coating. The pharmaceutical suspension according to (1).

(7) The coating substrate of the enteric coating, the water-insoluble coating or the gastric coating is at least one selected from methacrylic acid copolymers, aminoalkyl methacrylate copolymers and ethylcellulose. (6)
The pharmaceutical suspension according to Item.

(8) The pharmaceutical suspension has a single dose of 5
The pharmaceutical suspension according to any one of items (1) to (7), wherein the amount is from 50 to 50 ml.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION A suspension preparation for treating cirrhosis of the present invention means a suspension and a syrup described in the Japanese Pharmacopoeia, and the concentration thereof is also specified in the Japanese Pharmacopoeia. Range.

The active ingredients in the suspension preparation of the present invention are three kinds of branched-chain amino acids consisting of isoleucine, leucine and valine. Isoleucine is not particularly limited as long as it satisfies the standards of the Japanese Pharmacopoeia, but is usually produced by fermentation to a particle size of about 1 mm or less, and has a D50 of 3 to 350 μm. Especially 5
What is adjusted to 0 to 350 μm is used,
It is not limited to those of such origin. Similarly, leucine is not particularly limited as long as it satisfies the standards of the Japanese Pharmacopoeia, but is usually produced by fermentation or extraction, and is crushed to have a particle size of about 1 mm or less, D50 is 3 to 350 μm, especially 50 to 3
Those prepared to 50 μm are used, but are not limited to those of such origin. Similarly, valine is not particularly limited as long as it satisfies the specifications of the Japanese Pharmacopoeia, but usually crushed particles of about 1 mm or less particle size produced by fermentation or synthesis, It is used, but is not limited to those of such origin.

The mixing ratio of isoleucine / leucine / valine is generally in the range of leucine (1.9 to 2.2) and valine (1.1 to 1.3) when isoleucine is 1. However, the mixing ratio is not limited to the above, and the mixing amounts can be appropriately increased or decreased. As described above, the particle size of isoleucine, leucine and valine is D50 of 3 to 3.
The thickness is preferably 350 μm, particularly preferably 50 to 350 μm, but any particle having a particle size up to about 500 μm can be used.

The sour agent used in the suspension preparation of the present invention includes citric anhydride, citric acid, malic acid, tartaric acid, D-tartaric acid, ascorbic acid, succinic acid, maleic acid, malonic acid, L-glutamate hydrochloride, Organic acids such as acetic acid and lactic acid. Particularly preferred are citric anhydride, citric acid, malic acid, tartaric acid, D-tartaric acid, and ascorbic acid. In general, a sour agent of an inorganic acid such as hydrochloric acid, which is often used, has an insufficient effect of correcting a unique bitterness or a specific odor such as isoleucine. The amount of the sour agent to be added is not particularly limited as long as the effect of imparting a unique bitterness such as isoleucine or a specific odor is exerted, and is usually 0.05% based on the total amount of the suspension preparation.
(W / V) to 5% (W / V) and 0.25% (W / V) to 25% (W / V) for three types of branched chain amino acids.

In the suspension of the present invention, at least one suspending agent selected from the group consisting of cellulose derivatives, polyvinyl alcohol, gelatin, agar and tragacanth powder is used. Examples of the cellulose derivative include hydroxypropylmethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, carmellose, carmellose sodium, carmellose calcium, crystalline cellulose, crystalline cellulose and carmellose sodium.

The range of the amount of the suspending agent used is 0.1 to 5.0% (W / V), preferably 0.3 to 3.0% (W / V) based on the total volume of the suspension preparation. ), And 0.5 to 25.0% (W / V), preferably 1.5 to 1
5.0% (W / V). In addition, carboxylvinyl polymers used as suspending agents in ordinary pharmaceutical suspensions, partially or completely saponified polyvinyl alcohol, synthetic polymers such as polyvinylpyrrolidones, sodium alginate, propylene glycol alginate Natural polymers such as can also be used. In addition, surfactants such as polysorbate 80, polyoxyethylene hydrogenated castor oil 60, polyoxyl stearate 40, and inorganic substances such as magnesium metasilicate aluminate and light anhydrous silicic acid can be used.

In the suspension of the present invention, preservatives used in ordinary suspensions can be used in consideration of safety, compatibility with a branched-chain amino acid as a main drug, and the like.
Examples of preservatives that can be used include sorbic acid and its salts, benzoic acid and its salts, paraoxybenzoic acid and its esters, and the like.

Various flavoring agents such as sweeteners, fragrances and coloring agents can also be used. In the case of a suspension preparation, it is desirable to avoid using branched-chain amino acids consisting of isoleucine, leucine, and valine, since the use of commonly used sweeteners such as sucrose and fructose causes coloring due to the Maillard reaction during storage. . Erythritol, xylitol and the like also caused problems such as coloring. In addition, a commonly used acidulant of an inorganic acid such as hydrochloric acid, etc., did not have a sufficient effect of correcting the unique bitterness / specific odor possessed by branched-chain amino acids.

The suspension preparation of the present invention is prepared by using isoleucine, leucine and valine particles having the above-mentioned particle size in the above-mentioned mixing ratio, and mixing with water together with the above-mentioned suspending agent. There is no particular limitation on the mixing means for preparing the suspension preparation, and any mixing mechanism and model can be used as long as a uniform suspension can be obtained. High-pressure emulsifiers such as various homogenizers and microfluidizers, colloid mills and the like are preferably used, but universal mixers such as kneaders, pot mills, mortars and the like can also be used.

The particle size of the branched-chain amino acid particles used in the suspension preparation can be measured as follows. Laser diffraction / scattering type particle size distribution analyzer (LA- manufactured by Horiba, Ltd.)
Using 920), about 200 ml of 2-propanol is put into the circulating layer, circulated for 2 minutes while performing stirring and ultrasonic irradiation, and then blanking (no ultrasonic irradiation during measurement) is performed. Subsequently, the transmittance of the measured amino acid sample was 85 ± 5.
%. Circulation is performed for 2 minutes with stirring and ultrasonic irradiation, and measurement is performed 1 minute after the ultrasonic irradiation is stopped. The average particle diameter is a volume-based median diameter.

According to the present invention, in producing a pharmaceutical suspension preparation containing isoleucine, leucine, and valine, a sour agent and, if necessary, a flavoring agent and a sweetening agent are added, whereby the inherent bitterness of a branched-chain amino acid is obtained. -It is possible to supply a suspension formulation that reduces and masks the peculiar odor, makes it easier for patients to take, and greatly contributes to the improvement of compliance.

[0025]

EXAMPLE 1 To about 350 ml of purified water was added 3.50 g of hydroxypropylmethylcellulose and 0.25 g of crystalline cellulose carmellose sodium, and a disperser (IKA-L) was added.
abortechnik URTRA- TURRAX2
Dispersed in 5). 2.50 g of tartaric acid as a sour agent, 0.30 g of aspartame as a sweetener are added to this dispersion, and dimethylpolysiloxane 1.00 as a defoamer is added.
g, as a preservative, methyl paraoxybenzoate 0.03
g, propyl paraoxybenzoate (0.03 g) and polyethylene glycol 400 (2.50 g) as a thickener were added and dissolved with the above disperser. The liquid has a particle size of D5.
0 is 10 μm isoleucine 23.80 g, leucine 4
7.60 g and 28.60 g of valine were added, suspended with the above disperser, and purified water was added.
A small amount of yogurt essence and grapefruit essence were added to this solution in a volume of ml, and the solution was uniformly suspended with a microfluidizer (M-110Y manufactured by Tsukishima Kikai Co., Ltd.) to prepare a pharmaceutical suspension having a pH of 3.7.

Example 2 To about 450 ml of purified water, 4.90 g of hydroxypropyl methylcellulose and 0.35 g of crystalline cellulose carmellose sodium were added and dispersed by the disperser. 3.50 g of tartaric acid as a sour agent, 0.28 g of saccharin sodium as a sweetener, 35.00 g of trehalose, 1.40 g of dimethylpolysiloxane as an antifoaming agent, 0.04 g of methyl parahydroxybenzoate as a preservative, and paraoxybenzoic acid 0.04 g of propyl was added and dissolved with the disperser. The particle size D
5010 μm isoleucine 33.32 g leucine 6
6.64 g and 40.04 g of valine were added, suspended with the disperser, and purified water was added.
The volume was 0 ml. A small amount of yogurt essence and grapefruit essence was added to this solution, and the mixture was uniformly suspended with the microfluidizer to prepare a pharmaceutical suspension having a pH of 3.7.

Example 3 4.50 g of polyvinyl alcohol in about 350 ml of purified water
Was added and dispersed with the disperser. To this dispersion, 1.50 g of citric anhydride as a sour agent, 0.20 g of saccharin sodium as a sweetener, 25.25 g of mannitol.
Dimethylpolysiloxane 1.00 as antifoaming agent
g, as a preservative, methyl paraoxybenzoate 0.03
g, propyl paraoxybenzoate 0.03 g, and polyethylene glycol 400 2.50 g as a thickener.
And dissolved with the above disperser. 47.60 g of leucine having a particle size D50 of 10 μm and valine 2 were added to this solution.
8.60 g was added, and a small amount of yogurt essence and grapefruit essence was further added, and suspended with the microfluidizer. 28.55 g of isoleucine coated with an enteric coating was added to this solution, and the mixture was uniformly suspended with the above-mentioned disperser. Further, purified water was added to make a total volume of 500 ml. A suspension was prepared.

The enteric coating of isoleucine is a coating solution of isoleucine 200.0 g / methacrylic acid copolymer LD having a particle size D50 of 15 μm (Eudragit L30D-55 / polyethylene glycol 6000).
/ Purified water = 250.0 g / 7.5 g / 328.5 g) using a fluidized bed granulation coating apparatus [Freund Sangyo Co., Ltd. F
LO-1 type] according to a conventional method [coating amount: 20% (W / V)].

Example 4 To about 350 ml of purified water were added 3.50 g of hydroxypropylmethylcellulose and 0.25 g of crystalline cellulose carmellose sodium, and the mixture was dispersed with the disperser. 2.50 g of tartaric acid as a sour agent, 0.30 g of aspartame as a sweetener, 1.00 g of dimethylpolysiloxane as a defoaming agent, 0.03 g of methyl parahydroxybenzoate as a preservative, and 0.5 g of propyl paraoxybenzoate as a preservative. 03 g was added, 2.50 g of polyethylene glycol 400 was added as a thickener, and the mixture was dissolved with the disperser. To this solution, 28.60 g of valine was added, and trace amounts of yogurt essence and grapefruit essence were further added, and the mixture was uniformly suspended with the microfluidizer. 28.55 g of isoleucine and 52.36 g of leucine with this solution coated with an enteric coating.
Was added, and the mixture was uniformly suspended with a disperser. Further, purified water was further added to make a total volume of 500 ml, and once again dispersed well with a disperser to prepare a pharmaceutical suspension having a pH of 3.7.

The enteric coating of isoleucine was carried out in the same manner as in Example 1. The enteric coating of leucine was prepared by coating 200 g of leucine having a particle size D50 of 15 μm with a methacrylic acid copolymer LD coating solution (Eudragit L30D-55 / polyethylene glycol 600).
0 / purified water = 250 g / 7.5 g / 382.5 g) using a fluidized bed granulation / coating apparatus (Freund Sangyo FLO-1)
(Coating amount: 10% (W / V)).

Example 5 To about 350 ml of purified water, 3.50 g of hydroxypropylcellulose was added and dispersed with a disperser. 2.50 g of tartaric acid as a sour agent, 0.20 g of saccharin sodium as a sweetener,
00g was added and dissolved with a disperser. 47.60 g of leucine and 28.60 g of valine were added to this solution, suspended with a disperser, and 26.66 g of isoleucine with a water-insoluble coating was further added thereto, and uniformly suspended with a disperser. A small amount of yogurt essence and grapefruit essence was added to this solution, and purified water was added to make a total volume of 500 ml. This was once again dispersed well with a disperser to prepare a pH 3.7 pharmaceutical suspension.

The water-insoluble coating of isoleucine was prepared by coating 200 g of isoleucine having a particle size D50 of 15 μm with a coating solution of ethyl cellulose (ethyl cellulose / triethyl citrate / ethanol / purified water = 100 g / 30.
0 g / 1309.9 g / 561.0 g) was coated by the fluidized bed granulation coating apparatus according to a conventional method [coating amount: 5% (W / V)].

Example 6 10.00 g of gelatin was added to about 380 ml of purified water.
The mixture was heated to 0 ° C and dissolved with stirring. Put this solution at 25 ° C
After cooling, 5.00 g of tartaric acid, 1.00 g of sodium saccharin, 100.00 g of mannitol, 0.05 g of methyl parahydroxybenzoate, and 0.05 g of propyl paraoxybenzoate were added and stirred to dissolve. To this solution were added 95.20 g of isoleucine (particle size D50: 94 μm), 190.40 g of leucine (particle size D50: 94 μm), and 114.40 g of valine, and the mixture was stirred and suspended using a spatula.
Purified water was added to adjust the total volume to 1250 ml. Further, trace amounts of yogurt essence and grapefruit essence were added and mixed to prepare a pharmaceutical suspension having a pH of 3.4.

Example 7 10.00 g of gelatin was added to about 380 ml of purified water.
The mixture was heated to 0 ° C and dissolved with stirring. Put this solution at 25 ° C
After cooling, 5.00 g of tartaric acid, 1.00 g of sodium saccharin, 100.00 g of mannitol, 0.05 g of methyl parahydroxybenzoate, and 0.05 g of propyl paraoxybenzoate were added and stirred to dissolve. 95.20 g of isoleucine (particle size D50: 285 μm), 190.40 g of leucine (particle size D50: 313 μm), and 114.40 g of valine were added to this solution, and the mixture was stirred and suspended using a spatula. Purified water was added to adjust the total volume to 1250 ml. Further, trace amounts of yogurt essence and grapefruit essence were added and mixed to prepare a pharmaceutical suspension having a pH of 3.4.

Example 8 8.00 g of gelatin was added to about 240 ml of purified water,
The mixture was heated to ℃ and dissolved with stirring. After cooling this solution to 25 ° C., 4.00 g of tartaric acid and sodium saccharin 1.
60 g, L-menthol 0.08 g, methyl paraoxybenzoate 0.04 g, propyl paraoxybenzoate 0.
04 g was added and stirred to dissolve. 76.16 g of isoleucine (particle size D50: 285 μm), 152.32 g of leucine (particle size D50: 313 μm), and valine 9 were added to this solution.
1.52 g was added and the mixture was stirred and suspended using a spatula. Purified water was added to make the total volume 800 ml. Further, trace amounts of yogurt essence and grapefruit essence were added and mixed to prepare a pharmaceutical suspension having a pH of 3.6.

Example 9 1.20 g of agar was added to about 100 ml of purified water, and the mixture was heated to boiling and dissolved while stirring. After cooling this solution to 25 ° C,
Tartaric acid 1.20 g, saccharin sodium 0.24 g,
40.00 g of trehalose was added and stirred to dissolve. Isoleucine (particle size D50: 285 μm) 2
3.80 g, leucine (particle size D50: 313 μm) 4
7.60 g and 28.60 g of valine were added, and the mixture was stirred and suspended using a spatula. Purified water was added to make the total volume 250 ml. Further, trace amounts of yogurt essence and grapefruit essence were added and mixed to prepare a pharmaceutical suspension having a pH of 3.5.

Example 10 1.00 g of gelatin was added to about 35 ml of purified water.
The mixture was heated and dissolved with stirring. After cooling this solution to 25 ° C., 0.20 g of acetic acid and 0.10 g of sodium saccharin were added.
g, mannitol 10.00 g, methyl paraoxybenzoate 0.005 g, propyl paraoxybenzoate 0.0
05 g was added and stirred to dissolve. 9.52 g of isoleucine (particle size D50: 285 μm), 19.04 g of leucine (particle size D50: 313 μm) and valine 1 were added to this solution.
1.44 g was added, and the mixture was stirred and suspended using a spatula. Purified water was added to make the total volume 125 ml. Further, trace amounts of yogurt essence and grapefruit essence were added and mixed to prepare a pharmaceutical suspension having a pH of 4.0.

Example 11 10.00 g of gelatin was added to about 380 ml of purified water,
The mixture was heated to 0 ° C and dissolved with stirring. Put this solution at 25 ° C
After cooling, glutamate hydrochloride 0.70 g, saccharin sodium 1.00 g, mannitol 100.00 g,
0.05 g of methyl paraoxybenzoate and 0.05 g of propyl paraoxybenzoate were added and stirred to dissolve. Isoleucine (particle size D50: 285 μm) was added to this solution.
20 g, leucine (particle size D50: 313 μm)
40 g and 114.40 g of valine were added, and the mixture was stirred and suspended using a spatula. Purified water was added to adjust the total volume to 1250 ml. Further, trace amounts of yogurt essence and grapefruit essence were added and mixed to prepare a pharmaceutical suspension having a pH of 3.3.

Comparative Example 1 To about 450 ml of purified water, 4.90 g of hydroxypropyl methylcellulose and 0.35 g of crystalline cellulose carmellose sodium were added and dispersed with a disperser. To this dispersion, 0.28 g of saccharin sodium as a sweetener, 35.00 g of trehalose, 1.40 g of dimethylpolysiloxane as an antifoaming agent, 0.04 g of methyl parahydroxybenzoate and 0.04 g of propyl paraoxybenzoate as preservatives were added. Melted with parser. Isoleucine 3 having a particle size D50 of 10 μm
3.32 g, leucine 66.64 g, valine 40.04
g was added and suspended with a disperser, and purified water was further added to make a total volume of 700 ml. To this solution, trace amounts of grapefruit essence and yogurt essence are added, and the mixture is uniformly suspended with a microfluidizer.
A pharmaceutical suspension of H5.8 was prepared.

Comparative Example 2 To about 450 ml of purified water, 4.90 g of hydroxypropyl methylcellulose and 0.35 g of crystalline cellulose carmellose sodium were added and dispersed with a disperser. To this dispersion were added 0.56 g of saccharin sodium as a sweetener, 35.0 g of trehalose, 1.40 g of dimethylpolysiloxane as an antifoaming agent, 0.04 g of methyl parahydroxybenzoate and 0.04 g of propyl paraoxybenzoate as preservatives. Melted with parser.
This solution contains 33.3 isoleucine having a particle size D50 of 10 μm.
2 g, leucine 66.64 g, and valine 40.04 g were added, suspended with a disperser, and purified water was further added to make a total volume of 700 ml. Add a small amount of grapefruit essence and yogurt essence to this solution,
Suspension evenly with microfluidizer, pH
A pharmaceutical suspension of 5.8 was prepared.

Comparative Example 3 10.00 g of gelatin was added to about 380 ml of purified water.
The mixture was heated to 0 ° C and dissolved with stirring. Put this solution at 25 ° C
After cooling, saccharin sodium 1.00 g, mannitol 100.00 g, methyl parahydroxybenzoate 0.0
5 g and propyl paraoxybenzoate 0.05 g were added,
Stir and dissolve. Add isoleucine (particle size D5)
0: 285 μm) 95.20 g, leucine (particle size D5
0: 313 μm) 190.40 g, valine 114.40
g was added and stirred with a spatula to suspend. Purified water was added to adjust the total volume to 1250 ml. Further, trace amounts of yogurt essence and grapefruit essence were added and mixed to prepare a pharmaceutical suspension having a pH of 5.8.

Comparative Example 4 10.00 g of gelatin was added to about 380 ml of purified water.
The mixture was heated to 0 ° C and dissolved with stirring. Put this solution at 25 ° C
After cooling, sodium saccharin (2.00 g), mannitol (100.00 g), methyl parahydroxybenzoate (0.09 g) were added.
5 g and propyl paraoxybenzoate 0.05 g were added,
Stir and dissolve. Add isoleucine (particle size D5)
0: 285 μm) 95.20 g, leucine (particle size D5
0: 313 μm) 190.40 g, valine 114.40
g was added, and the mixture was stirred and suspended using a spatula. Purified water was added to adjust the total volume to 1250 ml. Further, trace amounts of yogurt essence and grapefruit essence were added and mixed to prepare a pharmaceutical suspension having a pH of 5.8.

Experimental Example 1 The pharmaceutical suspensions obtained in Examples 1 to 11 and the pharmaceutical suspensions obtained in Comparative Examples 1 to 4 were administered to 5 adult male panelists while maintaining the blindness. The sensory evaluation was performed. Ease of taking, bitterness of branched-chain amino acids after taking,
The degree of aftertaste of the branched-chain amino acids was evaluated. The criteria are as follows. ◎: good or not at all worried ○: not very worried △: slightly worried or slightly bitter ×: hard to drink or bitter

[0044]

[Table 1]

[0045]

As can be seen from Table 1, the present invention makes it possible to prepare a medicinal suspension which is easy to take.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 47/12 A61K 47/12 47/18 47/18 47/22 47/22 47/26 47/26 A61P 1/16 A61P 1/16 (72) Inventor Akira Yabuki 1-1 Suzukicho, Kawasaki-ku, Kawasaki-shi, Kanagawa Prefecture Ajinomoto Co., Inc. Pharmaceutical Research Laboratories F term (reference) 4C076 AA22 AA42 BB01 CC16 DD38T DD41T DD43T DD49T DD61T DD69T EE11 EE12 EE32 FF22 FF25 FF52 4C206 AA01 AA02 FA44 MA02 MA03 MA05 MA10 MA43 NA09 ZA75

Claims (8)

[Claims] 1. A pharmaceutical suspension comprising three kinds of branched-chain amino acids consisting of isoleucine, leucine and valine as an active ingredient and at least one organic acid as a sour agent. 2. It contains three kinds of branched-chain amino acids consisting of isoleucine, leucine and valine as an active ingredient and at least one selected from citric acid, malic acid, tartaric acid and ascorbic acid as an acidulant. A pharmaceutical suspension characterized by the following: 3. The composition according to claim 1, further comprising a sweetener selected from the group consisting of saccharin sodium, glycyrrhizic acid, aspartame, mannitol and trehalose and / or a flavoring agent comprising at least one of menthol and ethanol. Item 3. The pharmaceutical suspension according to Item 1 or 2. 4. The pharmaceutical suspension according to claim 1, wherein the pH of the pharmaceutical suspension is 2.5 to 6.0. 5. The particle size D of the isoleucine and leucine
2. A structure according to claim 1, wherein 50 is 3 to 350 .mu.m.
The pharmaceutical suspension according to any one of claims 4 to 4. 6. The isoleucine or leucine having a particle size D50 of 100 μm or less is provided with a coating selected from an enteric coating, a water-insoluble coating, and a gastric coating.
The pharmaceutical suspension according to the above. 7. The coating substrate of the enteric coating, the water-insoluble coating or the gastric coating is at least one selected from methacrylic acid copolymers, aminoalkyl methacrylate copolymers and ethyl celluloses. The pharmaceutical suspension according to claim 6, wherein 8. The pharmaceutical suspension has a single dose of 5 to 5.
The pharmaceutical suspension according to any one of claims 1 to 7, which is 50 ml.