JPH0723304B2 - Pharmaceutical component-immobilized composition - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Purpose of the Invention (Field of Industrial Application) The present invention relates to a composition for immobilizing drug components.

The “drug component” described in the present specification refers to a drug component selected from a drug and a nutrition enhancer.

(Prior Art) Conventionally, a drug component has been used in various forms such as liquid, powder, fine granules, granules or tablets. However, liquid ones are inconvenient to transport and handle, powdery ones have poor handling properties such as fluidity and metering property, and a lot of labor and cost are required in the packaging process. Therefore, drug components are often formed into granules or tablets.

Further, for example, powdery or granular materials such as L-lysine, streptomycin, fructose, thiamine hydrochloride, difedtramine hydrochloride, etc., will absorb moisture when left in humid air and become sticky or solid. It is difficult to use, and there are drawbacks such that decomposition and coloring are promoted by moisture absorption and the like. Depending on the type of drug component, when bitterness such as quinine or theophylline is strong, sucrose or lactose may be added for the purpose of increasing the amount or imparting sweetness, but addition of sucrose or lactose causes caries. It is not desirable for health because it has high properties and high calorie content, and in the case of sucrose, problems such as hygroscopicity and coloring due to acid, alkali or heat occur.

(Problems to be Solved by the Invention) The present invention has a non-hygroscopic property and non-deterioration property even when left in the air, and is in a crystal-like state that is easy to package, handle and use, and is also suitable for administration. An object of the present invention is to provide a drug component-immobilized composition in which various drug components are immobilized in a state without any trouble.

(B) Structure of the Invention (Means for Solving the Problems) The present inventor has conducted various kinds of studies to solve the above problems, and as a result, the present inventors have determined that the drug component is in the crystals of meso-erythritol and / or It was possible to achieve the purpose by including it in the crystal and fixing it.

That is, the drug component-immobilized composition of the present invention contains the drug component between the crystals of meso-erythritol and / or between crystals.

Meso-erythritol according to the present invention has the structural formula Is a tetravalent sugar alcohol represented by a molecular weight of 122,
It is a white crystal with a melting point of 119 ° C. Its appearance is similar to that of granulated sugar, sucrose, soluble in water, non-digestible (low calorie), and non-cariogenic. Meso-erythritol (hereinafter simply referred to as “erythritol”) is contained in natural algae, mushrooms, etc., and is also contained in small amounts in sake, wine, soy sauce and the like. According to the panel test results, the sweetness intensity and sweetness quality are slightly weaker than sucrose,
Slightly stronger than glucose, equivalent to about 75-80% sweetness intensity of sucrose, the mouthfeel is similar to that of sucrose, but the aftertaste is less sweet than sucrose. In addition, erythritol is chemically stable as it does not turn brown due to acid or alkali.

Erythritol is a fermentation method using glucose as a substrate, n-
It can be produced by a fermentation method using paraffin as a substrate, a method of reducing tartaric acid, a method of oxidizing cellulose or starch with periodate and then hydrogenating and hydrolyzing the same.

The immobilization composition of the present invention is one in which a drug component is contained in the crystals of erythritol and / or between the crystals to immobilize, and a typical method for producing the immobilization composition is a drug. It is a method of precipitating erythritol crystals from a supersaturated aqueous solution of erythritol to which components have been added.

That is, when a crystal of erythritol is grown and precipitated from a supersaturated aqueous solution of erythritol to which a drug component is added, the additive component is contained in the generated crystals and / or between crystals, and the immobilization composition of the present invention is obtained. Easily obtained. In this case, as long as the erythritol aqueous solution is in a supersaturated state, the precipitation of crystals can be continued. Therefore, it is desirable to precipitate the erythritol saturated solution having a relatively high concentration containing the drug component while cooling.

For precipitation of the erythritol crystals, either the static crystallization method or the fluidized crystallization method can be used. However, the static crystallization method gives crystals having a higher content of the drug component.
In this case, the size of the erythritol crystals precipitated and the amount of the drug component contained in the crystals and / or between the crystals are
Since it varies depending on the degree of supersaturation of the erythritol aqueous solution, the cooling rate, the stirring conditions, etc., the size of the crystals and the content of the drug component can be adjusted to some extent by controlling these conditions. Further, the content of the drug component can be adjusted by controlling the addition ratio of the drug component to the erythritol aqueous solution.

The crystal tank in the fluidized crystal method may be either an open type or a vacuum type. When crystallizing by adding a drug component having a large amount of volatile components, the standing method is preferred. Since a supersaturated aqueous solution of erythritol can precipitate crystals in a wide range of liquid temperature of 20 to 70 ° C, when immobilizing a drug component containing a component that is volatile easily, erythritol at a relatively low temperature is immobilized. It is desirable to add a drug component to the aqueous solution so as to cause crystal precipitation.

Erythritol crystals that have been precipitated from a saturated aqueous solution at a relatively low temperature for a long time using a static method are large and flat, and have a so-called "rock-sugar" -like appearance. If necessary, the crushed product is crushed to make the particle size uniform, so that a beautiful immobilization composition of crystals that closely resembles sucrose crystals can be obtained.

Described below are representative examples of producing the immobilizing composition of the present invention using the static crystallization method, the drug component is usually added to an erythritol aqueous solution having a concentration of 30% by weight or more, preferably 50% by weight or more. . For example, in the case of producing an immobilizing composition of the present invention in which vitamin B ₂ is immobilized, vitamin B ₂ powder is added to an aqueous erythritol solution having a temperature of 70 ° C. and a concentration of 50% by weight and 0.02 to 4% by weight, preferably Is 0.1-2
% Of the erythritol is added and dissolved, and the mixture is allowed to stand at room temperature and cooled to precipitate erythritol crystals. In this case, a small amount of microcrystals of erythritol may be added as a seed crystal to start crystallization, but it is possible to easily start crystallization without adding the crystal (however, in the case of the fluidized crystallization method, Crystallization is easy.)

The saturated concentrations of the erythritol aqueous solution at various temperatures are as shown in the table below.Therefore, in the case of precipitating crystals while cooling by the above-mentioned cooling, the amount of erythritol contained in the starting erythritol aqueous solution is used for the final cooling. The amount of erythritol excluding the amount of erythritol corresponding to the saturated concentration at temperature begins to precipitate as crystals.

Saturation concentration of erythritol aqueous solution Temperature Saturation concentration 80 ° C 73.2% by weight 60 ° C 61.8 〃 40 ° C 46.8 〃 20 ° C 33.2 〃 If the supersaturation of the erythritol aqueous solution that causes crystal precipitation is too high, microcrystals will form during crystal growth It is easy to obtain a product with uneven crystal grain size. In such a case, the cooling rate of the erythritol aqueous solution is controlled to prevent the degree of supersaturation from becoming excessive.

Then, a static crystallization method in which 1% by weight of powdered vitamin B ₂ was added and dissolved in an aqueous solution of erythritol at a temperature of 70 ° C and a concentration of 50% by weight and left at room temperature and then cooled to 5 ° C in a refrigerator In the case of crystal precipitation in (1), a composition having vitamin B ₂ having a crystal grain size of about 1 to 5 mm immobilized in about 6 hours was obtained. The solids yield in this case (ie Was 37%.

Further, the immobilizing composition obtained by the above-mentioned method, which contains a particularly hygroscopic drug component such as L-lysine, streptomycin, glyceryl salicylate, and vitamin B ₁ , further comprises a seed crystal of the immobilizing composition. Used as
When crystals are grown in the supersaturated erythritol aqueous solution (without addition of the drug component) using the above-mentioned stationary method, an outer layer consisting of only erythritol crystals is formed on the outer periphery of the immobilization composition containing the drug component. Thus, the immobilizing composition having such a bilayer structure has extremely low hygroscopicity even if the drug component itself has high hygroscopicity.

Another method for obtaining an immobilizing composition having a remarkably low water content and low hygroscopicity when left in the air is that the immobilizing composition obtained as described above is vacuum dried. Is a method in which erythritol or erythritol to which a relatively small amount of sugar or sugar alcohol is added is immersed in a heating melt, and the immobilizing composition is coated with the melt. The coating of the immobilization composition obtained by this method has an outer layer formed of erythritol or a mixture of erythritol and sugar or sugar alcohol on the outer periphery of erythritol crystals (that is, the immobilization composition) containing a drug component. Since it has a two-layer structure, its hygroscopicity is significantly reduced.

(Examples) Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1 100 g of an aqueous erythritol solution having a concentration of 55% by weight had a liquid temperature of 70
When cooled to ℃, add vitamin B ₂ powder in various proportions of 0.5 to 4 g as shown in the table below, mix well and leave to stand at room temperature for 4 hours to allow crystals to grow. After further growing the crystal in the refrigerator at 5 ° C. for 2 hours, the produced crystal and the mother liquor were separated. The sugar solution adhering to the surface of the separated crystal was washed with an alcohol aqueous solution having a concentration of 70% by weight at 5 ° C., and then vacuum dried at 70 ° C. for 3 hours. The vitamin B ₂ content of each of the obtained crystals was as shown in the table below.

The obtained vitamin B ₂ -containing erythritol crystals having a particle size of 32 mesh sieve to 80 mesh sieve are powder B ₂
Compared with the above, the meterability and fluidity were remarkably good.

Example 2 An immobilizing composition was obtained in the same manner as in Example 1 except that 10 g of glycerin was used instead of vitamin B ₂ .

The produced crystal amount was 35 g, and the glycerin content in the produced crystal was 0.4% by weight.

Example 3 100 g of an erythritol aqueous solution having a concentration of 60% by weight has a liquid temperature of 75
When cooled to 0 ° C, 5 g of L-lysine hydrochloride powder was added,
After mixing well, the crystals were grown for 5 hours while allowing to cool at room temperature, and the crystals were further grown for 4 hours in a refrigerator at 5 ° C., and then the produced crystals were separated from the mother liquor. The sugar solution attached to the surface of the separated crystal was washed with an aqueous alcohol solution having a concentration of 70% by weight at 5 ° C., and then vacuum dried at 70 ° C. for 3 hours.

The content of L-lysine hydrochloride in the obtained crystals was 0.20% by weight.
Met. Next, this crystal was immersed in an erythritol melt at 120 ° C. to coat the crystal surface with erythritol. When the obtained surface-coated crystals and L-lysine hydrochloride powder were allowed to stand in air at 30 ° C. and RH 79% for 2 weeks, the moisture absorption amount was 0.20% by weight for erythritol-coated crystals, -Lysine hydrochloride powder was 18.20% by weight. Further, the L-lysine hydrochloride powder had a peculiar weak odor, whereas the erythritol-coated crystals were completely odorless.

(C) Effect of the Invention The immobilizing composition of the present invention has excellent handleability, has little change with time such as moisture absorption even in the air, and has a beautiful crystalline appearance.

Claims (1)

[Claims] 1. A drug component-immobilized composition in which a drug component is contained between crystals of meso-erythritol and / or between crystals.