JP2934695B2 - Solid preparation - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a solid preparation, and more particularly to a solid preparation containing an amino acid, an amino acid salt, an amino acid derivative and a peptide alone or in a mixture in the fields of food, medicine, feed and the like.

[0002]

2. Description of the Related Art Amino acids, amino acid salts, amino acid derivatives (hereinafter, may be simply referred to as amino acids) and peptides are used for medical nutrition for fortification, oral and tube administration for patients with renal or hepatic failure. Amino acid preparations for different disease states and nutritional compositions for infants and diet food materials, health foods,
Widely used as functional foods. Furthermore, amino acids and peptides are also used in veterinary drugs for administration to animals after being mixed with cosmetics and feeds.

However, are amino acids and peptides such as branched-chain amino acids such as leucine, isoleucine and valine, basic amino acids such as lysine and arginine, sulfur-containing amino acids such as methionine, tryptophan, histidine and phenylalanine highly bitter? Or it has a bad taste that is difficult to take. Therefore, solid preparations containing the above-mentioned various amino acids and peptides are often subjected to pharmaceutical processing to reduce or mask bitterness and bad taste. Conventionally, the bitterness and bad taste of amino acids have been achieved by adding sugars and sugar alcohols. However, when saccharides and amino acids coexist, the Maillard reaction causes deterioration in quality such as color change over time and decrease in content. Therefore,
An amino acid-containing composition which is easy to take and has good storage stability, in which α-L-aspartyl-L-phenylalanine methyl ester is added in place of saccharides has been disclosed (Japanese Patent Application Laid-Open No. Sho 6).
0-199365).

[0004] However, when it is necessary to take a large amount for a long period of time, or when taking it in a form added to food, it is necessary to completely mask the bitterness and bad taste of amino acids and peptides. Coated preparations in which the surface of a peptide is coated with various coating materials are known. However, conventional coating preparations have a problem that they are colored over time or have a poor taste even when coated with a coating material, resulting in a poor feeling of taking.

[0005] As a preparation for solving such a problem, amino acids and peptides are tableted or granulated, and then the surface is coated with a coating material having low reactivity with amino acids and peptides, and then sugar or sugar is further added. Multi-layer coated preparations coated with sugar alcohol sweeteners are conceivable. However, in order to manufacture the multi-layer coated preparation, two types of coating steps having different manufacturing conditions are required, and the manufacturing time becomes longer, and automation is difficult due to different coating conditions. Furthermore, in the case of granules, a small amount of agglomerates of mutually adhered granules are formed during the step of coating the protective layer. The lumps are easily separated by the mechanical stress applied in the step of coating the protective layer or a subsequent step, and are incorporated into most of the coated granules coated without agglomeration. However, the coated granules that have once become agglomerates have a problem in that the protective layer is partially peeled off, and when the surface is coated with sugar and sugar alcohol, only the part where the protective layer has been peeled is colored in spots. . In the step of coating the protective layer, it is possible to manufacture under a coating condition that does not generate aggregates. However, such coating conditions cause problems such as an extremely long time required for the coating process and an increase in loss of the coating material, and cannot be adopted from the viewpoint of manufacturing cost.

On the other hand, it is difficult for children and the elderly to take large amounts of solid preparations such as powders, granules and tablets. In such a case, a dry syrup that can be taken in a liquid form at the time of use is mentioned as one of the preferable dosage forms. Generally, dry syrups contain sucrose, sorbitol and mannitol as sweetening excipients in addition to the active ingredient. However, when a simple substance or a mixture of amino acids and peptides is used as an active ingredient, a color change and a decrease in content over time occur as in the case of the aforementioned granules and tablets, and long-term stability cannot be maintained.

[0007]

SUMMARY OF THE INVENTION An object of the present invention is to provide a solid preparation containing, as an active ingredient, a simple substance or a mixture of amino acids and peptides in the fields of food, medicine, feed, etc., with excellent productivity and long-term stability. An object of the present invention is to provide a solid preparation that maintains the properties.

[0008]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies in view of the above-mentioned circumstances, and as a result, have found that the above-mentioned problems can be solved by using trehalose as an additive for a solid preparation, thereby completing the present invention. Was completed.

That is, the present invention provides excellent productivity and long-term stability containing at least one active ingredient selected from amino acids, amino acid salts, amino acid derivatives and peptides and trehalose as an additive. It is intended to provide a solid preparation to be kept. An embodiment of the present invention includes providing a solid preparation that forms a coating layer containing trehalose and a sweetener on at least one active ingredient selected from amino acids, amino acid salts, amino acid derivatives, and peptides.

The trehalose used in the present invention includes α, α
-Trehalose, α, β-trehalose or β, β-trehalose, but naturally occurring α, α-trehalose is preferred. Further, as the amino acids, for example, leucine, isoleucine, branched-chain amino acids such as valine, lysine, basic amino acids such as arginine,
Cystine, sulfur-containing amino acids such as methionine, phenylalanine, aromatic amino acids such as tyrosine, tryptophan,
Examples include various amino acid derivatives such as heterocyclic amino acids such as histidine and sulfur-containing amino acid derivatives such as taurine. Examples of peptides include peptides such as di- and tripeptides, living hormones and derivatives thereof, and partial degradation products of animal and plant proteins.

[0011] Trehalose is known to have a slight sweetness. Then, as a result of examining the flavoring effect of trehalose in detail, it was found that, unlike sucrose, mannitol, and sorbitol, the sweetness was too small to obtain the flavoring effect. Then, as a result of examining the taste-correcting effect by using trehalose in combination with a known sweetener, it was found that the combined use of trehalose and sweetener exhibited a sucrose-like natural sweetness. Therefore, by using trehalose as a coating material together with a sweetener instead of sucrose or sugar alcohol, the surface of amino acids and peptides can be directly coated without coating with a protective layer to obtain a flavoring effect. The sweetener may be any as long as it does not cause a change in blending such as a Maillard reaction, and saccharin sodium salt, α-L
-Aspartyl-L-phenylalanine methyl ester, erythritol and the like.

In addition, trehalose may be used as a coating material instead of hydroxypropylcellulose, methylcellulose and the like conventionally used as a protective layer for the amino acids and peptides. Further, by using trehalose and a sweetener as a sweetening excipient instead of sucrose and sugar alcohol, a large amount of amino acids and peptides can be easily taken, and a dry syrup having little deterioration in quality over time can be obtained.

The solid preparation of the present invention can contain various vitamins, calcium compounds, trace elements such as zinc, copper, iron, manganese and magnesium, and antibiotics, in addition to amino acids and peptides. .

The solid preparation of the present invention is generally used as tablets, granules and dry syrups for oral administration of foods, pharmaceuticals and the like. For example, nutrient enhancers containing essential and non-essential amino acids as active ingredients, pharmaceuticals and foods for liver diseases containing branched-chain amino acids and the like as active ingredients, liver function enhancement using alanine, glutamine, ornithine, arginine and the like as active ingredients And pharmaceuticals and foods for the purpose of promoting aldehyde metabolism. These preparations can be manufactured according to a known method.

[0015]

[Action] Trehalose is a pharmaceutically stable disaccharide, and does not cause Maillard reaction even when it coexists with amino acids. Therefore, by using this as an additive,
It is possible to provide a solid preparation which has a long-term stability and is excellent in feeling of taking, while simplifying the production process of a solid preparation containing amino acids and peptides as active ingredients and improving productivity.

[0016]

【Example】

Example 1 A binder was added to a mixed powder of branched-chain amino acids (leucine: isoleucine: valine weight ratio 1: 1: 1), and the mixture was extruded and granulated (screen diameter: 0.7 mm inner diameter, EXDC-
Granules were prepared using a No. 60 model manufactured by Fuji Paudal Company. A fluid granulation coating device (FL-10)
A coating layer corresponding to 10% of the weight of the granules was formed with a coating material containing α, α-trehalose as a main component shown in Table 1 with a mold (manufactured by Freund Corporation) to obtain an amino acid-containing granule.

[0017]

[Table 1]

Example 2 21 g of an amino acid mixed powder having the amino acid composition shown in Table 2
, 200 g of α, α-trehalose, 1 g of α-L-aspartyl-L-phenylalanine methyl ester, 50 g of erythritol, and 0.5 g of polyvinylpyrrolidone were each mixed in a fluidized granulation coating apparatus (FL-10, manufactured by Freund Corporation). Thereafter, a wet liquid (purified water: ethanol volume ratio of 1: 1) was sprayed and granulated.
The granulated product was dried to obtain an amino acid-containing dry syrup having an average particle size of about 500 μm.

[0019]

[Table 2]

Example 3 250 g of L-arginine, 1 g of talc and 1 g of hydrated silicon dioxide were mixed, and a plain tablet having an outer diameter of 8.5 mm and a weight of about 252 mg was tableted with a tableting machine (Correct 12 HUK, manufactured by Kikusui Seisakusho). . This uncoated tablet is used as an inner core, and a medium sugar coating layer containing 50 mg of α, α-trehalose, 10 mg of talc, 5 mg of precipitated calcium carbonate, 1.5 mg of gum arabic and 0.5 mg of gelatin per 252 mg of inner core, and sucrose as a main component A sugar-coating layer was formed by a pan coating method to obtain a sugar-coated tablet containing 250 mg of L-arginine per tablet.

Next, an amino acid-containing preparation for testing was prepared. Comparative preparation 1 Amino acid-containing granules were prepared in the same manner as in Example 1 except that sucrose (the same amount) was used instead of α, α-trehalose in Example 1 and α-L-aspartyl-L-phenylalanine methyl ester was removed. Was obtained, and the resultant was designated as Comparative Preparation 1.

Comparative Preparation 2 The procedure of Example 2 was repeated, except that sucrose (the same amount) was used in place of α, α-trehalose and α-L-aspartyl-L-phenylalanine methyl ester was used. An amino acid-containing dry syrup was obtained, which was designated as Comparative Preparation 2.

Test Example 1 The amino acid-containing granules of Example 1, the dry syrup of Example 2, Comparative Formulations 1 and 2 were each stored in a sealed glass bottle at 60 ° C., and the yellowing degree over time ( Δb) was measured with a color difference meter (# 80 manufactured by Nippon Denshoku Industries Co., Ltd.), and the results are shown in FIG. For both types of comparative preparations,
A remarkable increase in the degree of yellowing (Δb) due to heating abuse was observed, but the degree of yellowing of the granules and dry syrup preparations of the present invention was slight, and no color change was observed. From these results, it was found that the amino acid-containing solid preparation according to the present invention has excellent pharmaceutical stability.

[0024]

According to the present invention, there is provided a solid preparation comprising a simple substance or a mixture of amino acids and peptides as an active ingredient, which has excellent productivity, maintains long-term stability, and is excellent in feeling of taking. be able to.

[Brief description of the drawings]

FIG. 1 is a diagram showing a change in coloring over time.

──────────────────────────────────────────────────続 き Continued on the front page (58) Fields surveyed (Int.Cl. ⁶ , DB name) A61K 31/195 A61K 9/16 A61K 9/20 A61K 9/50 A61K 47/26 CA (STN) MEDLINE (STN )

Claims (1)

(57) [Claims] 1. A mixed powder of amino acids is contained as an active ingredient.
Bare granules with a coating material based on trehalose
Amino acid-containing granules characterized by being coated by coating
Agent.