JP2574176B2 - Yellow solid color - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a yellow solid colored material obtained by using a C-type riboflavin butyrate ester as a pigment and coloring an object to be colored in the field of food or medicine. .

2. Description of the Related Art Problems to be solved by the conventional technology and the invention In the fields of food and medicine, there are many solid products. These are usually colored to improve the image as a product or to identify the medicine.

Generally, when coloring food or medicine in yellow,
Food dye No. 4 of food tar color, food yellow No. 4 aluminum lake (Fifth edition food additive), yellow bengalara (Extra-European component standard; 1986 version), and riboflavin (Tokoku 46)
26989, JP-B-61-3224) and riboflavin butyrate.

Examples of natural pigments include powdered sun yellow No. 3 (carotenoid type; San-ei Chemical) and powdered sun yellow No. 2 (flavonoid type; San-ei chemical; Japanese Patent Publication No. 50-148562).

Of these, riboflavin is used as a yellow colorant and a nutritional enhancer for foods such as dairy products and processed wheat products, but tends to be faint to light under alkaline conditions and easily discolored.

In addition, when riboflavin is used for coloring solid preparations such as granules and tablets, there is a disadvantage that the riboflavin itself feels bitterness when taken, and the color itself becomes yellow-orange rather than lemon-yellow.

Further, riboflavin butyrate has no bitterness but is fat-soluble, and is therefore only used exclusively for oily foods such as margarine, cheese and cream.

In addition, even with this ester, it was difficult to produce a bright, yellowish yellowish orange lemon.

Means for Solving the Problems The present inventors have used riboflavin butyrate, which is said to be the most safe, as a dye, and
As a result of intensive studies on the application to coloring of pharmaceuticals, etc., among the riboflavin butyrate esters of type A, B, and C, in particular, type C is extremely effective for coloring foods and pharmaceuticals, and is obtained. The colorants obtained were found to have no color unevenness and to exhibit a lemon-based bright bright yellow, and as a result of further studies, the present invention was completed.

That is, the present invention relates to (i) a yellow solid color product obtained by coloring a substance containing a drug component with a C-type riboflavin butyrate, and (ii) a C-type riboflavin butyrate which is a capsule or tablet. A coloring method characterized by coloring a yellow solid colored substance colored with an ester and (iii) a powdered or granular drug component or a substance to be colored such as a capsule or a tablet with C-type riboflavin butyrate.

The C-type riboflavin butyrate used in the present invention is described in Pharmaceutical Journal, 108 (1), 39-43 (1988).

The literature reports three types of riboflavin butyrate esters of type A, type B, and type C, which are orange-red, khaki, and yellow solids, respectively, and are known to have different crystal systems.

Among them, the C-type riboflavin butyrate is formed by pouring a methanol solution of the A-type riboflavin butyrate into water with vigorous stirring.

In the present invention, a commercially available ethanol solution of Form A riboflavin butyrate is dispersed in water,
C-type riboflavin butyrate was obtained.

When this C-type riboflavin butyrate was applied to coloring of foods, pharmaceuticals, etc., it was found that it was unexpectedly bright and bright lemon-based yellow which had never existed before.

The riboflavin butyrate used in the present invention means riboflavin tetrabutyrate, which is a natural colorant, and is described in the Standards for Extraterrestrial Components (1986 edition) and the Official Standards for Food Additives (5th Edition). ing.

In the present invention, this ester is first dissolved in ethanol to form a solution, which is then dispersed in water to form a suspension, which is used as a coloring liquid and further as a granulating liquid.

Alternatively, the suspension may be filtered and vacuum-dried to form a powder.

In addition, various forms can be selected according to the properties of the material to be applied.

When used as a suspension, the suspension is usually obtained by adding an ethanol solution of the ester to water and dispersing the mixture under stirring. Conversely, a method in which water is added to an ethanol solution of the ester with stirring and dispersed may be used.

 The dispersion temperature is usually performed at room temperature.

The concentration of the ester in the ethanol solution is adjusted to be approximately 1 to 70% by weight.

The suspension is almost 100 parts by weight of ethanol solution per 100 parts by weight of water.
Not more than 40 parts by weight, preferably not more than 40 parts by weight is used.

Then, using the suspension thus prepared,
Coloring can be applied to the object to be colored.

For coloring, most commonly, a method of adding a suspension to a material to be colored and mixing uniformly, or a method of uniformly spraying the suspension on the material to be colored can be employed.

When the yellow solid color product of the present invention is produced using a suspension of riboflavin butyrate ester of type C, the amount of the suspension of riboflavin butyrate ester of type C is about 0.001% of the material to be colored.
-10% by weight, preferably 0.001-5% by weight.

If the amount is less than 0.001% by weight, the coloring may be insufficient, and fading may easily occur.

On the other hand, if the content exceeds 10% by weight, the amount of the suspension, particularly water, becomes large, which may hinder granulation or increase the working time, which may be undesirable.

The amount of the C-type riboflavin butyrate suspension used is:
It depends on the concentration of the ethanol solution at the time of preparing the suspension, the amount of water used when dispersing this ethanol in water, the granulation method, the properties of the material to be colored, and the like. I just need.

When the object to be colored is in the form of a powder, the powder can be colored while being granulated.

Granulation includes a wet stirring granulator (eg, a pony mixer; manufactured by Inoue Seisakusho Co., Ltd.), a vertical granulator, manufactured by Fuji Sangyo Co., Ltd.) and a fluidized bed granulator (eg, Glatt; manufactured by West German Glatt Co., Ltd.). Flow coater; Freund Sangyo Co., Ltd., Aeromatic; Fuji Sangyo Co., Ltd.)
Etc. can be used.

In this case, the suspension of the present invention may be appropriately added to a conventionally used binder (for example, starch paste, hydroxypropylcellulose, hydroxypropylmethylcellulose,
Methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, gelatin, pullulan, sucrose) and the like.

In addition, these binder solutions may be added to the material to be colored together with the suspension.

Powder or granular material (10 μm to 1 mm
Are often used.

When the powder is colored while being granulated, a granule colored yellow is obtained.

This product can be appropriately sized to obtain granules having various particle sizes.

For example, when the material to be colored is melted and in a liquid state during the manufacturing process, such as a shell of a capsule, a suspension can be added to the liquid to manufacture the material.

When the powdered C-type riboflavin butyrate is used, for example, it can be directly added to a binding solution at the time of granulation or mixed with a material to be colored.

In addition, those which become liquid during the manufacturing process can be directly added to the liquid to be manufactured.

The amount of the powdered C-type riboflavin butyrate used may be appropriately determined depending on the target product to be produced, but may be up to about 50% by weight based on the obtained target product, including the case where riboflavin butyrate itself is used as the main drug. it can.

The coloring object in the present invention means a raw material or a primary processed product (granules, uncoated tablets, etc.) used in the field of food or pharmaceuticals.

Also, C-type riboflavin butyrate can be applied to the shell portion of a hard capsule or a soft capsule.

In particular, a powdery drug component serving as a raw material for producing a solid preparation can be preferably used.

Examples of such coloring materials include ascorbic acid, sodium ascorbate, calcium ascorbate, vitamin A, vitamin D, thiamine nitrate, pyridoxine hydrochloride, nicotinamide, calcium pantothenate,
Pharmaceutical ingredients such as biotin, vitamin B ₁₂ , acetaminophen, dextromethorphan hydrobromide, aspirin, methylephedrine, aluminum hydroxide, magnesium oxide, such as sucrose, sorbitol, mannitol, dextrose, saccharin Sweeteners such as lemon lime, flavors such as fruit essence, excipients such as lactose, starch, microcrystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, PVP, calcium carboxymethylcellulose, such as magnesium stearate, stearic acid , Talc, powdered solids such as lubricants such as light anhydrous silicic acid, and granulated and molded products thereof.

According to the above-described method, a colored object in which the object to be colored is colored yellow is obtained. The yellow solid color product of the present invention can be used as it is as a solid preparation such as a food or pharmaceutical, for example, a powder or granule.

In particular, in the case of a yellow granulation, a yellow tablet can be obtained by directly or mixing with another drug and compressing with a conventional tablet machine.

In addition, a colored tablet can also be produced by adding a C-type boflavin butyrate to a sugar-coated solution or a film solution during production of a sugar-coated tablet or a film tablet.

Effect of the Invention The yellow solid color product of the present invention has a feature of exhibiting a bright bright lemon-based yellow color without unevenness.

In addition, bitterness is not felt when it is contained in the mouth, and no coloring phenomenon in the mouth is observed.

In the method of the present invention, since an aqueous solvent, for example, an ethanol / water solvent having an ethanol concentration of usually 20 to 30% is used, it can be handled as a non-dangerous substance.

In particular, it has an excellent feature that it does not require the use of an explosion-proof granulator or dryer.

In addition, tablets and the like processed using the yellow solid coloring material of the present invention together with other drug components not only have no color unevenness but also have a feature that a bright lemon color is maintained as it is.

When this tablet is, for example, a vitamin-based drug preparation, the yellow colored substance of the present invention can be incorporated not only as a coloring agent but also as a base drug.

Hereinafter, the present invention will be described more specifically with reference to examples.

The formula of Hunter used to show light stability in the examples is as follows ("Weathering Light and Color", by Suga Choichi, Suga Test Press, 1977).

ΔE: color difference ΔL: lightness difference Δa, Δb: hue difference and saturation difference The amount of change from the initial when the sample was irradiated with a xenon fade meter for 10 hours was calculated using a color computer SM.
The color difference (ΔE) was calculated using a -1 type (Suga Test Instruments Co., Ltd.).

In Examples, riboflavin butyrate which is a raw material of C-type riboflavin butyrate is expressed as RTB.

Example 1 Granules and Tablets Colored in Yellow According to the formulations (a) to (c) described in Table 1, 500 g of powdered sugar containing 30% by weight of ascorbic acid powder was colored while being granulated, and turned yellow. Obtained colored granules (16 mesh passing
95%).

The granulator used was a fluidized bed granulator (FD-3S; non-explosion-proof type; manufactured by Fuji Sangyo Co., Ltd.), and the granulation conditions were as shown in Table 2.

Further, magnesium stearate (0.7% by weight) was added as a lubricant to the yellow-colored granules and mixed.
This was tableted using a tablet machine (Collect 19K, manufactured by Kikusui Seisakusho Co., Ltd.) to produce three types of flat corner tablets (a) to (c) (weight: 50).
0mgl tablet, diameter 10mm) was manufactured.

Table 3 shows the appearance and light stability (dye ΔE) of the obtained tablets (a) to (c).

According to the production method of the present invention, it is possible to obtain a yellow-colored granule and a lemon-based bright yellow-colored tablet without using an explosion-proof granulator.

And since this tablet has a color difference value of 5 or less, it has no practical problem in light fastness.

Example 2 Granules and Granules Colored in Yellow 1 kg of a powder consisting of acetaminophenone (40% by weight), lactose (30% by weight) and denbun (30% by weight) was mixed with a vertical granulator (FM-VG-10; The suspension was charged into an RTB suspension (0.1 g of RTB in 10 ml of alcohol), and the resulting solution was dispersed in 150 ml of water.
(Equivalent to weight%) was added, and the mixture was colored while being granulated to obtain a granule colored yellow.

After drying this with a vacuum dryer (Kusunoki Seisakusho Co., Ltd.), a power mill (P-3; Showa Chemical Machinery Co., Ltd.)
The mixture was sieved to obtain 90% granules that passed through a 16 mesh.

For comparison, 1 kg of the above powder and 0.1 g of RTB powder simply added and mixed were also granulated using 150 ml of water,
Similarly, granules were obtained.

 Table 4 shows the appearance and light stability of the obtained granules.

Example 3 Granules and tablets colored yellow Ascorbic acid, sodium ascorbate, powder containing sorbitol as a main component (15% by weight of ascorbic acid,
10 kg of sodium ascorbate (15% by weight, sorbitol 60% by weight) was charged into a fluidized bed granulator / dryer (Glat WSQ-15; manufactured by Okawara Seisakusho Co., Ltd.), and this was suspended in RTB suspension (RTB).
Dissolve 20 g in 150 ml of ethanol and add this solution to 600 ml of water
The powder was colored while granulating the powder by spraying.

Subsequently, 100 g of starch was dispersed in 1,900 ml of water,
The granules were further granulated while spraying the size liquid heated to 0 ° C.

The granules colored yellow were dried and sized, and then tableted in the same manner as in Example 1 to produce tablets.

For comparison, tablets were produced using granules obtained by granulating using a dispersion obtained by simply dispersing 20 g of RTB in 600 g of starch paste solution (starch: water = 1: 19). Table 5 shows the appearance and light stability of both tablets.

Example 4 Granules colored yellow Yellow 1 kg of crystalline granulose is coated on a coating pan (12 inches;
Kikusui Seisakusho Co., Ltd.), RTB 0.1g and ethanol 1
The resulting mixture was sprayed with a suspension of 500 ml of water and sprayed with 1 kg of an equal mixture (spray agent) of ascorbic acid and powdered sugar.

Coating was performed until the diameter of the particles became about 5 mm, and then vacuum drying (manufactured by Kusunoki Seisaku Co., Ltd.) was performed to obtain granules.

For comparison, granules were produced by spraying with water using a mixture of 0.1 g of RTB and 1 kg of a spray.

The appearance and light stability of both the obtained granules were as shown in Table 6.

Example 5 Yellow-colored tablets (sugar-coated tablets) Tablets (diameter obtained by compression of powder containing lactose and starch as main components (lactose 70% by weight, starch 30% by weight))
9.5mmφ, weight 250mg, 5,000 tablets) coated pan (12
Inch; manufactured by Kikusui Seisakusho Co., Ltd.).

At this time, the sugar coating liquid was granulose, talc, pullulan,
A sugar-coated tablet 1 made of water to which a suspension of RTB (0.1 g of RTB dissolved in 10 ml of ethanol and dispersed in 50 ml of water) was added was used.

Finishing was carried out with a syrup solution to give a tablet with a finished weight of 450 mg.

For comparison, a sugar-coated tablet was obtained by sugar-coating using a solution obtained by simply mixing 0.1 g of RTB powder with a sugar-coated solution, and finishing with a syrup solution.

The appearance and light stability of the obtained both sugar-coated tablets were as shown in Table 7.

Example 6 Film tablets colored yellow Yellow lactose and starch tablets (9.5 m diameter) described in Example 5
The film was coated with a film liquid containing C-type riboflavin butyrate by using Axela Coater 24 (manufactured by Monesty Co.) using mφ, weight 250 mg, 40,000 tablets.

Examples of the used film liquid include hydroxypropyl methylcellulose [TC-5 (R); Shin-Etsu Chemical Co., Ltd.
3L of a film solution consisting of titanium oxide, polyethylene glycol 6000 and water, and a suspension of RTB (0.15 g of RTB dissolved in 1 ml of ethanol and dispersed in 10 ml of water). Was.

 A film tablet with a finishing weight of 260 mg was obtained.

For comparison, a film tablet was produced by simply adding 0.15 g of RTB to 3 l of the film solution.

The appearance and stability of both furilm tablets obtained were as shown in Table 8.

Example 7 Film tablets colored yellow In place of the suspension of RTB, 0.3 g of RTB was dissolved in 3 ml of ethanol, and this was dispersed in 30 ml of water, filtered, and dried under vacuum (Kusuki Kikai Co., Ltd.) Tablet coating was performed in the same manner as in Example 6 except that the yellow powder of C-type riboflavin butyrate described above was used.

The manufactured film tablets had a finishing weight of 260 mg.

As a comparison, a film tablet was produced using a product obtained by simply adding 0.3 g of RTB to 3 l of the film solution.

The appearance and stability of the obtained film tablets were as shown in Table 9.

Example 8 Sugar-coated tablets colored in yellow In place of the suspension of RTB, sugar-coated tablets were prepared in the same manner as in Example 5, except that 1 g of the same RTB yellow powder as in Example 7 (containing 1 g of RTB) was used. Dragee was obtained.

As a comparison, a sugar-coated tablet was produced by using one obtained by simply adding 1 g of RTB to the sugar-coated liquid 1.

The appearance and stability of the obtained both sugar-coated tablets were as shown in Table 10.

Example 9 Yellow hard capsules 30 parts of water was added to 30 parts of gelatin and dissolved by heating.

On the other hand, 1 part of titanium oxide and 1 part of the yellow powder of RTB described in Example 7 (containing substantially 1 part of RTB) were dispersed in 10 parts of water using a homomixer (manufactured by Tokushu Kika Co., Ltd.). ,
Add to the aqueous gelatin solution and color.

A capsule pin is put into this solution, molded and dried,
Hard capsules.

The resulting capsule was colored bright lemon yellow.

Test Example X-ray diffraction of C-type riboflavin butyrate C-type riboflavin butyrate used in the present invention and
RTB to X-ray diffractometer RDA-C type (manufactured by Rigaku Denki; 40k
V, 40 mA) are shown in FIGS. 1 and 2.

This C-type riboflavin butyrate is described in “Pharmaceutical Magazine, 10
8 (1), 39-43 (1988) ".

The RTB used for obtaining the C-type riboflavin butyrate was the same as the A-type riboflavin butyrate described in “Pharmaceutical Magazine, 108 (1), 39-43 (1988)”.

[Brief description of the drawings]

FIG. 1 is a powder X-ray diffraction diagram of type C riboflavin butyrate. FIG. 2 is a powder X-ray diffraction diagram of RTB.

Claims (14)

(57) [Claims] 1. A yellow solid colored product obtained by coloring a substance to be colored containing a drug component with C-type riboflavin butyrate. 2. The yellow solid colored substance according to claim 1, wherein the substance to be colored, which is a powdery or granular drug component, is colored with C-type riboflavin butyrate. 3. The yellow solid colored product according to claim 1, wherein the drug component is a component containing ascorbic acid. 4. The yellow solid colored product according to claim 1, wherein the drug component is a component containing ascorbic acid and sodium ascorbate. 5. A yellow solid colored substance obtained by coloring a substance to be colored, which is a capsule or a tablet, with C-type riboflavin butyrate. 6. A coloring method comprising coloring a powdered or granular drug component or a substance to be colored, such as a capsule or a tablet, with C-type riboflavin butyrate. 7. A coloring method comprising coloring a powdery or granular drug component, or a substance to be colored such as a capsule or a tablet, with a suspension of a riboflavin butyrate ester ethanol solution dispersed in water. 8. The coloring method according to claim 7, wherein the amount of riboflavin butyrate used is about 0.001 to 10% by weight of the material to be colored. 9. A coloring method comprising coloring a powdery or granular drug component or a substance to be colored, such as a capsule or tablet, with a powdery C-type riboflavin butyrate. 10. A powdery or granular drug component or a substance to be colored, such as a capsule or tablet, is colored with a powdery C-type riboflavin butyrate obtained by vacuum-drying the suspension according to claim 7. A coloring method characterized in that: 11. The coloring method according to claim 6, wherein the substance to be colored is a powdery or granular drug component. 12. The coloring method according to claim 6, wherein the substance to be colored is a tablet. 13. The coloring method according to claim 6, wherein the coloring is performed while granulating the powdery or granular drug component. 14. A yellow-colored tablet obtained by tableting the yellow solid color product according to claim 2.