JP5964686B2 - Ascorbic acid granules - Google Patents

Description

  The present invention relates to ascorbic acid granules.

L-ascorbic acid is a substance that acts as vitamin C nutritionally. Furthermore, it is widely used as an antioxidant for foods. L- ascorbic acid (vitamin C) has a strong reducing ability in a water-soluble, superoxide (O ₂ ^-), hydroxy radicals (· OH), active oxygen such as hydrogen peroxide (H ₂ O ₂₎ to erase. The elimination of hydrogen peroxide in L-ascorbic acid is performed by the glutathione-ascorbic acid circuit. As represented by this circuit, even when L-ascorbic acid is oxidized to dehydroascorbic acid, it is reduced and regenerated to ascorbic acid by various enzymes to function catalytically. Therefore, it is effective for suppressing accumulation of oxidative stress in the living body. In recent years, it has been widely taken as a supplement for the purpose of maintaining health.

  L-ascorbic acid is a substance that exhibits strong acidity, and also exhibits strong reducibility, so that it reacts with these substances in a system in which water, oxygen, and metal coexist, and loses its activity as vitamin C. Promotes browning reaction by redox reaction. For this reason, when L-ascorbic acid coexists with other substances, it reacts with the substance and quickly loses its activity as vitamin C. For this reason, a method has been proposed in which L-ascorbic acid is used as a core substance and the surface thereof is coated with a hydrophobic substance. For example, Patent Document 1 (Japanese Patent Laid-Open No. 10-203965) discloses a technique in which L-ascorbic acid is used as a core substance and the surface thereof is coated with oils or waxes. Patent Document 2 (Japanese Patent Application Laid-Open No. 5-221859) discloses coated vitamin C granules in which vitamin C is used as a core substance and is coated in three layers, an oily fat layer, an edible film layer, and an oily fat layer. Since these prior art L-ascorbic acids are coated with water-insoluble oils, waxes and films, the granules can be mixed with or mixed with other ingredients such as granules such as metal salts, vitamins and proteins. Since it is difficult to react with these components even after tableting, the L-ascorbic acid can be kept stable, and the metal salt, vitamins, and proteins do not come into contact with the L-ascorbic acid, so that the brown color changes. It is said that such problems will not occur.

However, when a granule is prepared by coating L-ascorbic acid with the above technique, there is a problem that the concentration of L-ascorbic acid in the granule is relatively lowered. In order to prevent this, if the thickness of the coating layer is relatively thin, L-ascorbic acid inevitably flows out easily, or flows out through the coating layer, and tablets that are compressed into composite granules or composite granules. Causes problems such as a decrease in the activity of L-ascorbic acid, browning of the tablet, and coloring.
As a substance that has solved the problem of instability of L-ascorbic acid, there is a derivative of L-ascorbic acid. In particular, ascorbic acid stearate and ascorbyl palmitate, which are fatty acid esters of L-ascorbic acid, have been developed and are widely used as antioxidants for foods. The fatty acid ester of ascorbic acid is insoluble in water, and is slowly hydrolyzed in the presence of moisture to release L-ascorbic acid. Widely used as an agent. However, fatty acid esters of ascorbic acid have a large bulk specific gravity (bulk) and are not suitable for granulation. Moreover, since it is fat-soluble, it lacks immediate effect as vitamin C.

  As a result of intensive research on the preparation technique of granules coated with ascorbic acid as a core substance without reducing the relative concentration of L-ascorbic acid, the present inventors have found that when forming a coating layer, L-ascorbine It has been found that by using an acid fatty acid ester as a coating agent, a stable coated granule can be provided without reducing the relative concentration of L-ascorbic acid.

Japanese Patent Laid-Open No. 10-203965 Japanese Patent Laid-Open No. 5-221859

  An object of the present invention is to provide a stable L-ascorbic acid granule having L-ascorbic acid as a core substance and coated with a fatty acid ester of L-ascorbic acid. Another object of the present invention is to provide a composite granule containing granules coated with a fatty acid ester of L-ascorbic acid.

The present invention is as follows.
(1) L- ascorbate as a core material, oral granules coated with fatty acid esters of L- ascorbic acid.
(2) L- fatty acid esters of ascorbic acid, oral granules according to a L- ascorbyl palmitate or L- ascorbic acid stearate (1).
(3) the weight ratio of fatty acid esters of L- ascorbate and ascorbic acid granules is 1: 0.5 to 0.5: oral granules according to 1 which is (1) and (2).
(4) (1) to oral composite granules formulated with oral granules according to any one of (3).

According to the present invention, stable granules having a high L-ascorbic acid content can be obtained. Even if this granule coexists with the metal salt, peptide, etc. which brown with a conventional reaction with L-ascorbic acid, it is maintained stably.
Moreover, it becomes possible to mix | blend a metal salt, a peptide, etc. in the composite granule using this granule. Such granules can be combined with multiple components such as supplements containing vitamins, minerals, various extracts and the like.
In addition, the present invention stabilizes vitamin C, suppresses loss of activity during storage, and enables long-term storage.

The test image which confirmed the reactivity of the granule prepared by this invention and collagen peptide. It is the figure which measured L-ascorbic acid eluted from the granule of this invention and the L-ascorbic acid granule of a prior art with time.

In the present invention, “vitamin C” having the same meaning as the term “L-ascorbic acid” may be used in the following description.
The granule of the present invention is a granule in which L-ascorbic acid is used as a core substance and this is coated with a fatty acid ester of L-ascorbic acid. This granule can be used alone as an L-ascorbic acid (vitamin C) granule, or other nutritional component, a granule of a metal salt or an extract, or a drug that easily reacts with L-ascorbic acid such as coenzyme Q10. It can be mixed with granules and molded into tablets. Or what was mixed can be used as a granule.
In the conventional stabilization technique, since L-ascorbic acid was coated with oils, waxes, films, etc. for the purpose of stabilizing L-ascorbic acid, the relative concentration of L-ascorbic acid in the granules decreased. However, according to the present invention, this does not occur. In addition, stability can be maintained. The present invention prepares granules by coating L-ascorbic acid crystals as a core substance with a fatty acid ester of L-ascorbic acid. The fatty acid ester of L-ascorbic acid is preferably palmitic acid ester or stearic acid ester, particularly preferably palmitic acid ester.

  The L-ascorbic acid used in the present invention is preferably a crystallized high purity. As the food, those described in the official food additive “L-ascorbic acid” or equivalents thereof are used. Standard products that are usually listed in the Japanese Pharmacopoeia are used. In addition, as the fatty acid ester of L-ascorbic acid, in the case of palmitic acid ester or stearic acid ester, it is preferable to use a fatty acid ester that satisfies the standard defined in the Food Additives Official Document.

The crystal of L-ascorbic acid is used as a core substance as it is or granulated as necessary.
When the crystal of L-ascorbic acid is used as a core material as it is, the surface of the L-ascorbic acid crystal is coated with a fatty acid ester of L-ascorbic acid by a kneading granulation method.
As a granulator for kneading and granulating, it is preferable to use a granulator using an apparatus equipped with a kneading blade and a crushing blade. Examples of such a granulator include a triaxial kneading granulator provided by Shinagawa Kogyo Co., Ltd.
In coating, the weight ratio of L-ascorbine crystals and L-ascorbic acid fatty acid ester is preferably 1: 0.5 to 0.5: 1. By doing in this way, the relative amount of L-ascorbic acid per granule will be about 80-61 mass%. This is because the content of L-ascorbic acid in the granules is only 60 to 33% by mass when other coating agents are used in the same amount. Thus, since this invention can set a relative concentration high, when ingesting the same amount of L-ascorbic acid, the size of a tablet and the amount of packaging of a granule can be decreased. Also, when other components are included, the content can be increased with the same capacity.

  After granulating L-ascorbic acid, the production method of the original granule of ascorbic acid when coated with a fatty acid ester of L-ascorbic acid is not particularly limited, and a wide variety of methods known in the art can be used. Specifically, examples thereof include an extrusion granulation method, a rolling granulation method, a stirring granulation method, a fluidized bed granulation method, a rolling fluidization granulation method, and a kneading granulation method. Among these, the kneading granulation method is preferable.

As a granulator for kneading and granulating, it is preferable to use a granulator using an apparatus equipped with a kneading blade and a crushing blade. Examples of such a granulator include a triaxial kneading granulator provided by Shinagawa Kogyo Co., Ltd.
The bulk density (bulk specific gravity) of the L-ascorbic acid raw granules when granulated is not particularly limited, but is preferably 0.35 to 0.75 g / mL, more preferably 0.40 to 0.65 g / mL, 0.5 to 0.63 g / mL is particularly preferable. When the bulk density is less than 0.35 g / mL, the bulk becomes high, and when the obtained final granule is used as it is as a granule, there is a possibility that the amount of sachet per packet increases. On the other hand, when the bulk density exceeds 0.75 g / mL, the bulk is reduced, and a heavy granule is obtained, and the amount of packaging is also reduced.

  The 50% particle size of the L-ascorbic acid original granule is not particularly limited, but is preferably 400 to 700 μm, more preferably 450 to 650 μm, and particularly preferably 500 to 600 μm. If the 50% particle size is larger than 700 μm, it becomes difficult to drink when it is made into a granule, and if it is smaller than 400 μm, it tends to cause aggregation and agglomeration of the original granules, which may hinder coating.

  Next, the obtained L-ascorbic acid original granule is dried. The drying treatment is preferably performed until the moisture content of the original granule becomes 2% or less. The drying method is not particularly limited, and any method can be adopted as long as it is a drying method used for ordinary granule drying, but a vacuum drying method and a blow drying method are preferable. The vacuum drying method and the blast drying method may be carried out independently or in combination. However, it is particularly preferable to use a vacuum drying method because the moisture of the granules can be removed as much as possible.

    Next, the surface of the dried raw granule is coated with a fatty acid ester of L-ascorbic acid. In coating, the weight ratio of L-ascorbic acid primary granule to L-ascorbic acid fatty acid ester is set to 1: 0.5 to 0.5: 1. By doing in this way, the relative amount of L-ascorbic acid per granule will be about 80-61 mass%. This is because the relative concentration can be set high compared to 60 to 33% by mass when other coatings are used in the same amount. Therefore, when the same amount of L-ascorbic acid is ingested, the tablet size and granules The amount of the medicine package can be reduced to half or less. Moreover, when other components are included, the content can be increased.

  The L-ascorbic acid granule of the present invention does not change even when stored over time, the appearance hardly changes, and reacts even when coexisting with a protein, peptide, vitamin, or metal salt that reacts with L-ascorbic acid. Without L-ascorbic acid decreasing or browning. Odor is not generated. Further, even when dispersed in water, L-ascorbic acid in the granules does not easily elute into water.

EXAMPLES Next, although an Example and a test demonstrate this invention further in detail, this invention is not limited at all by these examples.
Examples and Comparative Examples Preparation of granules In the combination of ratios shown in Table 1, L-ascorbic acid palmitate (manufactured by DSM) is coated with crystalline L-ascorbic acid (food additive standard; manufactured by BASF Japan) as a core substance, Prepared. The coating was performed using a high-speed stirring granulation method or a triaxial kneading granulation method. The operation of both methods was as follows.

High speed stirring granulation method
150 g of L-ascorbic acid and L-ascorbic acid palmitate were combined in the combinations shown in Table 1 and granulated at high speed with 99% anhydrous ethanol dropwise with a high speed mixer (LFS-GS-2J, Fukae Pautech). The obtained granule was dried for 12 hours or more on a condition of 50 ° C. in a blowing constant temperature dryer. After drying, the granules were sized to obtain granules.

Triaxial kneading granulation method L-ascorbic acid and L-ascorbic acid palmitate are combined in the combination of Table 1 and 150 g is premixed in a triple master (TMGV-5, Shinagawa Kogyo), then 99% absolute ethanol 120g was added and granulation was implemented. After the completion of granulation, primary drying was performed for 10 minutes under a jacket temperature of 50 ° C. and a vacuum condition, and the obtained granules were dried for 12 hours or more under a condition of 50 ° C. in a blowing constant temperature dryer. After drying, the granules were sized to obtain granules.

2. Evaluation (1) Formulation appropriateness By observing the appropriateness of the formulation by both methods, it is evaluated by the state of granules and the amount of residual adhesion to the device, and is evaluated in three stages as ◎ excellent formulation suitability, possible formulation ○, difficult formulation × The results are shown in Tables 2 and 3. The obtained granule was observed with a scanning electron microscope, and the coating state of L-ascorbyl palmitate on the granule surface was observed. There was no substantial difference between the above methods.

(2) Stability test L-ascorbic acid and L-ascorbic acid palmitate are blended in the ratios shown in Table 1, and the granules subjected to coating operation by a high-speed stirring granulation method react with L-ascorbic acid to turn brown. Collagen hydrolyzed peptide powder (manufactured by Zerais Co., Ltd.) is weighed so as to have the same amount of ascorbic acid in the granules shown in Table 1, sealed in a polyethylene bag, 40 ° C., and humidity 75 The sample was allowed to stand for 7 days under the condition of% and observed. The results are shown in Table 4. Moreover, the image which image | photographed the reaction condition on the 7th day of the collagen peptide of the granule prepared using L-ascorbic acid and L-ascorbic acid palmitate in the ratio of 1: 1 and the granule of only ascorbic acid is shown in FIG.
The granules of the present invention did not change at all when mixed with collagen hydrolyzed peptides.

(3) L-ascorbic acid elution test from granules Using L-ascorbic acid and L-ascorbyl palmitate blended at a ratio of 1: 1, and using the granules coated by the triaxial kneading granulation method, The dissolution test of L-ascorbic acid was conducted.
The dissolution test was based on the dissolution test method (paddle method) described in the 16th revised Japanese Pharmacopoeia.
900 ml of metaphosphoric acid solution was used as a test solution, and each granule was accurately weighed and carried out at a rotation speed of 100 rpm and a test solution temperature of 37 ° C. The test solution was filtered with Fine Filter (F-72; Toyama Sangyo Co., Ltd.) every 10 minutes, and the elution amount was measured from the absorbance at 243 nm to determine the elution rate.
As a control, the measurement was performed using commercially available L-ascorbic acid granules (manufactured by NOF Corporation) coated with a conventional coating technique.

Dissolution test conditions
Test solution: 0.05% aqueous metaphosphoric acid (37 ° C)
Measurement wavelength 243nm
Paddle method Rotation speed: 100rpm
An ascorbic acid equivalent of 18 mg was weighed and used for the dissolution test.

The measurement results are shown in FIG.
In the L-ascorbic acid C granule of the present invention, it is confirmed that L-ascorbic acid elutes quickly, and about 100% moves to the eluate side after about 15 minutes from the start of elution. In the oil-coated granules, the elution was about 76% 3 hours after the start of elution and about 90% after 12 hours.

From the above test results, it was found that the ascorbic acid of the present invention is stable in an environment such as the air, and when ingested, it is quickly eluted in the stomach and digestive tract and absorbed quickly.

Claims (4)

The L- ascorbic acid as a core material, oral granules coated with fatty acid esters of L- ascorbic acid. Fatty acid esters of L- ascorbic acid, oral granules according to claim 1, wherein the L- ascorbyl palmitate or L- ascorbic acid stearate. The weight ratio of fatty acid esters of L- ascorbic acid and ascorbic acid in the granules is 1: 0.5 to 0.5: oral granules according to claim 1 or 2 is 1. Oral composite granules formulated with oral granules according to any of claims 1-3.