JPH0827033A - Erythritol-containing solid agent - Google Patents

Abstract

PURPOSE:To obtain a solid agent such as a tablet or a capsule by uniformly blending an erythritol having properties such as sweetness, fine powder-forming property, low hygroscopic property and stability as an additive for medicine such as a vehicle or a damp proof material with a pharmacodynamic ingredient. CONSTITUTION:This solid agent contains a pharmacodynamic ingredient and erythritol in a homogeneous state and contains preferably 1-99wt.% of erythritol. Furthermore, erythritol is quadrivalent sugar alcohol and is used as a sweetener having ultra-low energy and has crystals or powder with 122 molecular weight and 119 deg.C melting point and soluble in water and has good-quality sweetness and hardly cause diarrhea compared with other sugar alcohol and has noncariogenic property and does not cause browning reaction with amino acids or protein-based medicines. Erythritol exists in fruits, lichens, mushrooms, etc. An example of a preparation using the solid gent is to mix theophylline of 1kg with erythritol of 2.5kg, crystalline cellulose of 0.5kg and calcium stearate of 0.02kg, grind the mixture and form into tablets so as to become 200mg per tablet.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention uses tablets, capsules, pills, granules, powders, troches, erythritol as pharmaceutical additives such as excipients, moisture-proofing agents, stabilizers, etc. The present invention relates to solid agents such as extracts.

[0002]

2. Description of the Related Art Oral pharmaceuticals generally reach the digestive organs after administration, are dissolved and then absorbed, and are distributed in the living body to exert their medicinal effects. For oral administration, solid agents such as tablets, capsules, powders, granules, and lozenges have been conceived, and a wide variety of pharmaceutical additives have been developed in order to prepare these solid agents and enhance their functionality. Has been done. BACKGROUND ART In the production of solid preparations such as tablets and granules, various kinds of additives have been conventionally used according to the purpose. These additives are used for the purpose of increasing the amount and shaping of drugs that are not suitable for formulation such as tablets and tablets with a low effective dose, and for preventing moisture and stabilizing highly hygroscopic drugs such as thiamine hydrochloride. It is widely used for the purpose of taste and flavoring of drugs having bitterness such as ibuprofen, cimetidine, theophylline, and quinine, and drugs having an odor such as cholestyramine.

Among these additives, saccharose, fructose, glucose, lactose, maltose, dextrin and other sugar additives have almost no safety problems unlike chemically synthesized products, and are handled as crystals or powders. Easy and cheap,
Used frequently. However, these saccharides have problems that they have hygroscopicity themselves, or cause coloration and change of components due to acid, alkali, and heat in the coexistence with amino acids and protein drugs. Furthermore, it has cariogenicity and high calories, which is not preferable from the viewpoint of health.

Glycerin, as an additive to replace sugars,
There are sugar alcohols such as sorbitol, xylitol, maltitol and mannitol. Since these sugar alcohols do not have a reducing group, they do not normally cause browning with amino acid or protein drugs and are not cariogenic. However, sugar alcohols such as sorbitol and maltitol are less prone to browning, but have a problem that they are more hygroscopic than sucrose and the like. When the hygroscopicity is high, there remains a problem in mechanical suitability for fine powder, and it also has an unfavorable problem that it also affects the storage stability of the preparation such as tablets. Moreover, since glycerin is liquid, it is not suitable for the production of solid agents. Furthermore, if these sugar alcohols are ingested too much, diarrhea is likely to occur, and their use must be restricted. Mannitol is the only sugar alcohol with low hygroscopicity, and it shows extremely low hygroscopicity. However, mannitol has the drawback of being too low in water solubility and expensive.

Conventionally, as an example of using erythritol as a drug, a coated solid drug obtained by forming a coating layer of a coating material containing meso-erythritol (erythritol) as a main component on the surface of a solid drug (Japanese Patent Laid-Open No. 1-268628). ) And a drug component between erythritol crystals and / or eutectic crystals.
-268627) is known. However, until now, no example has been known in which a drug and crystals or powder of erythritol are uniformly mixed and then made into a solid agent such as a tablet.

[0006]

DISCLOSURE OF THE INVENTION The present invention does not cause browning with an amino acid or protein drug, easily forms a fine powder with low hygroscopicity, is less likely to cause diarrhea, and has an appropriate water solubility. To find a pharmaceutical additive that possesses non-cariogenic and low-calorie properties.

[0007]

As a result of earnest research, the inventor of the present invention has found erythritol as a material having these properties and characteristics. Erythritol has properties such as film forming property, fine powder forming property, low hygroscopicity, and easy crystallinity, and has an appropriate solubility. Such a property has a sufficient function as a pharmaceutical additive such as an excipient, a moisture-proofing agent, a stabilizer, and a sugar-coating agent during the production of a solid agent, and is particularly easy to form a fine powder. , And its low hygroscopicity surpasses other sugars and sugar alcohols already used as pharmaceutical additives. That is, the present invention is a solid agent comprising a medicinal component and erythritol uniformly, and more specifically, the medicinal component and 1
It is a solid agent uniformly containing -99% by weight, preferably 5-95% by weight of erythritol. The solid preparation of the present invention is produced by a conventional method using erythritol instead of or as a part of the conventionally used sugar or sugar alcohol. At this time, erythritol alone may be used as a pharmaceutical additive, but in general, it is often used in combination with other excipients, moisture-proofing agents, and stabilizers.

Erythritol in the present invention is a tetravalent sugar alcohol, which is an ultra-low energy sweetener that has recently begun to appear on the food market, and has a molecular weight of 122 and a melting point of 1.
Crystals or powder at 19 ℃, soluble in water, having high-quality sweetness, less prone to diarrhea than other sugar alcohols such as sorbitol, non-cariogenic, amino acids,
It is a sugar-based material that does not cause browning reaction with protein-based drugs. Erythritol is found in the natural world in fruits such as pears, grapes, watermelons, and melons, as well as in lichens, mushrooms, and in fermented foods such as wine, sake, and soy sauce. Is a highly safe material that has been used as food.

Erythritol, when taken orally,
Most of them are absorbed from the small intestine and rapidly excreted in the urine without any metabolism, and only some of them are not absorbed reach the large intestine and undergo fermentation by enterobacteria to become short-chain fatty acids. , It is known that this is absorbed from the large intestine and becomes an energy source. Erythritol is a type of sugar alcohol similar to sorbitol, but unlike other sugar alcohols, it is well absorbed from the small intestine, so the amount reaching the large intestine is small and osmotic diarrhea is unlikely to occur. The likelihood of diarrhea is usually thought to be 1/3 to 1/4 that of sorbitol. On the other hand, other sugar alcohols such as sorbitol are hardly absorbed in the small intestine and reach the large intestine as they are, so that osmotic diarrhea is likely to occur, and the amount of fermentation in the large intestine is large. Is inevitably high. On the other hand, erythritol absorbed in the small intestine is not directly metabolized in the body and is excreted in the urine as it is, so it does not become energy at all, and only slightly fermented in the large intestine becomes energy. The value is extremely low, and is reported to be 0.3 kcal / g or less.
(Published by Food Chemistry Shimbun, separate volume, Food Chemical-4, Sweeteners, p.188-194) Erythritol is not only physically and chemically stable, but erythritol administered to the living body as described above is mostly used. It is excreted outside the body without being caused, and has no adverse effect on the living body at this time. Therefore, it is highly preferable as a pharmaceutical additive which is required not to affect the living body.

Since erythritol is a fine powder having extremely low hygroscopicity, it has excellent compatibility with the main ingredient, pharmaceutical powder, and is suitable for solid preparations such as tablets, powders, pills, granules, troches, and extracts. It is most suitable as an excipient, a moisture-proofing agent, and a stabilizer during production. In particular, it has good mechanical suitability for tableting in tablet production, and exhibits excellent effects as an excipient. As shown in Test Example 1, tablets produced using erythritol as an excipient have very low hygroscopicity and excellent stability.

[0011]

EXAMPLES The present invention will be described in more detail below with reference to examples, reference examples and test examples, but the present invention is not limited to these examples. Example 1 Theophylline (1 kg), erythritol (2.5 kg), crystalline cellulose (0.5 kg) and calcium stearate (0.02 kg) were added, and the mixture was pulverized for 5 minutes in a mixer, and then 1 tablet 200 m using a tableting machine.
Tablets were manufactured by tableting into g. Reference Example 1 (Production of Control Formulation) Example 1 using maltitol instead of erythritol
A tablet was produced in the same manner as in.

Example 2 1600 g of sodium valproate, 2000 g of erythritol and 160 g of gum arabic were thoroughly mixed, and then 650 g of an ethanol solution of 5% hydroxypropyl cellulose was added and kneaded. After drying this kneaded product with a hot air dryer at 60 ° C, 1000μ
Granules were manufactured by sizing through a m sieve. Example 3 The granules prepared in Example 2 were filled in gelatin capsules to prepare capsules.

Example 4 To 920 g of erythritol and 70 g of gum arabic, 10 g of sodium azulenesulfonate was added and mixed well with a mixer, and then compression molded using a tableting machine to produce a lozenge. This lozenge had a cool sensation and a refreshing sweetness, and an excellent ingestion feeling was obtained. Example 5 4950 g of erythritol was added to 50 g of dihydrocodeine phosphate and mixed well with a mixer, and then passed through a 500 μm sieve to prepare a powder.

Example 6 To 400 g of quinine hydrochloride, 600 g of erythritol and 50 g of hydroxypropyl cellulose were added and mixed well,
The pills were manufactured using the Narimaru. Example 7 200 g of the rotocon coarse powder is leached according to the percolation method using 35% ethanol as a leaching agent. The leachate was concentrated under reduced pressure, 200 g of erythritol was added, mixed well, and dried with warm air at 50 ° C to produce a dry extract.

Test Example 1 The tablets produced in Example 1 and Reference Example 1 were stored at room temperature under the condition of relative humidity of 85% for 7 days, and the weight change due to moisture absorption was measured. As a result, the weight change (moisture absorption rate) of the tablets containing erythritol was 0.15%, indicating extremely low hygroscopicity. On the other hand, the increase rate of tablets using maltitol, which is the control formulation, was 6.8%.

[0016]

EFFECTS OF THE INVENTION Due to the properties of erythritol, such as the refreshing sweetness, good fine powder-forming property, low hygroscopicity, and good stability, the solid preparation of the present invention hardly absorbs moisture and is very stable. And it is easy to take. Further, the erythritol according to the present invention is excellent in mechanical suitability for tableting, compression, etc., and therefore tablets and the like can be easily produced.

Claims (2)

[Claims] 1. A solid agent containing a medicinal component and erythritol uniformly. 2. The solid agent according to claim 1, wherein the solid agent contains 1-99% by weight of erythritol.