JPH10291933A - Calcium-supplying agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a calcium-supplying agent which foams without using a foaming agent and can efficiently allow bodies to absorb calcium by rapidly decaying in the stomach due to this foaming. Further, to obtain a calcium- supplying agent which is excellent in safety and has good texture due to preventing stimulation to mucosae in tongue, mouth and stomach and unpleasant feeling when it is ingested. SOLUTION: This agent is produced by mixing granules formed by granulating a mixture of 65.4 wt.%-89.4 wt.% of shell-burning calcium and 6.6 wt.%-22.5 wt.% of citric acid in an anhydrous alcohol with a mixed powder formed by compounding 2.0 wt.%-18.3 wt.% of shell-burning calcium produced by other processes different from the granulation process of the granules with 0.2 wt.%-3.5 wt/% of citric acid powder. Tablets are formed by pressing this mixture by tablet machines.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a calcium supplement for efficiently taking calcium.

[0002]

2. Description of the Related Art Conventionally, in an era when the Japanese diet is said to be satiety, it has become clear from the Ministry of Health and Welfare's National Nutrition Survey that power calcium is the only nutrient that is lacking. Calcium is usually taken from ordinary foods, dairy products, and drinking water that are consumed on a daily basis.However, changes in dietary habits reduce the intake of small fish, etc., and milk and cheese, etc. The dairy product intake is low, and the land of Japan is acidic soil due to its volcanic soil, and the calcium content of drinking water from growing plants and rivers is low. Will be insufficient.

[0003] In the current dietary life, there are many opportunities to consume processed foods and ready-to-eat foods. In these foods, phosphates are contained as food additives for the purpose of stabilizing quality, coloring, and preserving, and unconsciousness. Tend to consume too much phosphate in the meantime. When the excess phosphate absorbed in the body is excreted outside the body, it is excreted together with calcium in the blood in the form of calcium phosphate, so that the amount of calcium in the body decreases.

[0004] Calcium is a troublesome nutrient whose absorption rate in the body varies depending on age, sex exercise, intake of foods containing vitamin D, whether to be in the sun, intake of calcium absorption factors such as CCP, etc. It is. And, as evident from the results of the National Nutrition Survey conducted by the Ministry of Health and Welfare, the results indicate that calcium intake itself does not meet the nutritional requirements. Calcium intake has been declining year by year, and increasing calcium intake is urgently needed from the viewpoint of maintaining and improving the health of the people.

[0005] In particular, after menopause, the rate of calcium retention in the body decreases due to a decrease in female hormone secretion with age after menopause, and the symptoms such as stiffness, fracture easily, and brittle bone are likely to appear. These have been found to be due to insufficient calcium intake. At present, osteoporosis of the elderly, easily fractured children during development, fragile constitution, arteriosclerosis, calculus, nervousness such as stress and irritation, poor growth, etc., which are becoming social problems, lack of calcium intake. It is said to be one of the causes.

[0006] However, it is difficult for us Japanese to eat a sufficient amount of calcium to satisfy nutritional requirements in the daily diet, and in order to prevent various diseases caused by insufficient calcium intake, it is inevitable. It is necessary to supplement calcium in some way. Therefore, although there are calcium preparations in pharmaceuticals, most of them use calcium carbonate or organic acid calcium as a raw material. Because pharmaceuticals are intended for the prevention and treatment of disease, they are unsuitable for everyday use simply to compensate for the lack of intake of calcium as a nutrient. In addition, there is a problem in the daily use of pharmaceuticals in view of the nature and taste of the pharmaceuticals. In addition, even if it is a pharmaceutical product, it cannot be said that there is no significant difference in the absorbability in the body from general calcium supplement foods except for the case where it is directly administered to the blood as an injection, from the viewpoint of its components.

[0007] Further, as a calcium supply source as food, there are roughly three types of calcium phosphates such as animal bones and fish bones, calcium enhancers for food additives, and calcium carbonates such as shells.

[0008] Calcium phosphates such as animal bones and fish bones are used as raw materials for calcium supplements as bovine bone meal and fish bone powder. However, since they have a unique taste and smell, there is no problem in terms of palatability. Many. Also, since it contains phosphoric acid, calcium absorbed into the body is immediately excreted outside the body. As a result, calcium is difficult to store in the body, making it unsuitable as a calcium supplement source.

[0009] Calcium enhancers of food additives include calcium compounds of inorganic acids or organic acids.
These have a drawback that the proportion of calcium in the molecular weight is small, and in order to ingest a certain amount of calcium, it is necessary to ingest a large amount of the component, and it is difficult to ingest calcium at an efficiency of about . For example, calcium citrate (C ₁₂ H ₁₀
Ca ₃ O ₁₄ · 4H ₂ for O molecular weight 570.51), calcium Ca is not contained only 0.21g in 1g. Also,
Since these food additives are chemically synthesized products, there is a problem in terms of taste and side effects when taken in a single large amount. In addition, according to the Food Sanitation Law, when it is added to general foods except when it is added to special nutritional foods, it is usually used as 1% of food as calcium.
%. For this reason, it is inappropriate to use calcium supplement as a daily food

[0010] In the case of calcium carbonate such as shells, shells such as oyster shells such as boray and scallops are used as raw materials for calcium supplement foods. These shells are mainly composed of calcium carbonate, contain a small amount of calcium phosphate, other small amounts of hard proteins such as keratin and various minerals, and have a high calcium content.
g contains about 0.4 g of calcium. Therefore,
Suitable for use as a source of natural calcium supplements. Borei, an oyster shell, is widely known as a useful raw material for herbal medicine. In general, shells have little use at seafood processing sites and can only be discarded.However, using shells as a calcium source in this way is extremely difficult from the viewpoint of effective utilization of marine resources. It's worth it.

When shells are used as a raw material for calcium supplement food, "shell shell calcium" which is pulverized and powdered, and "shell calcined calcium powder which is pulverized and pulverized after baking the shell at a high temperature." There are two types of methods. Normally, shells such as oysters and scallops, which are natural calcium and mineral sources, have foreign substances such as proteins, algae, and shell pieces adhered around the shells, and do not remove these foreign substances in order to serve them for food. It causes coloring, off-flavors, decay and deterioration. For this reason, these foreign substances are removed by baking the shell at a high temperature. This is "shell calcined calcium".

[0012] As a result of the baking treatment of the shell, as shown in the following reaction formula, a part of the calcium carbonate CaCO ₃ , which is the main component of the shell, becomes calcium oxide CaO, and about 1 g of calcium is contained in 1 g of the baked shell. Contains 6 g and has a high calcium content, making it ideal for use as a raw material for calcium supplements. CaCO ₃ → CaO + CO ₂ ↑ This calcium oxide reacts with water to produce calcium hydroxide C
a (OH) ₂ . CaO + H ₂ O → Ca (OH) ₂

[0013]

However, calcium hydroxide produced by the above reaction exhibits strong alkalinity (about pH 11), is hardly soluble in water, and is partially gelled (jellified) in water. I do. In order for minerals such as calcium to be absorbed into the body, they need to be ionized. However, calcium agents (tablets or granules) containing calcined shell calcium as a main component are hardly soluble in water, so they have disintegration properties. It is bad and therefore hardly absorbed in the body. For this reason, even if ingested, it is excreted as it is in the feces as it is, or because it exhibits strong alkali, it stimulates the oral mucous membrane and tongue to feel a feeling of dryness, and stimulates the mucous membrane of the stomach to cause nausea There were drawbacks such as feeling uncomfortable.

[0014] The present invention is to solve the above-mentioned problems, and ingesting shell calcined calcium,
Conventional calcium is insoluble in water due to its insolubility or difficult to absorb due to high alkaline pH of shell calcined calcium. It is intended to promptly promote digestion and absorption, and to enhance calcium absorption in the body.

[0015]

SUMMARY OF THE INVENTION In order to solve the above-mentioned problems, the present invention provides a shell calcined calcium of 65.4 wt% or less.
89.4wt% and citric acid 6.6wt% ~ 22.5wt
% Granulated with anhydrous alcohol, and 2.0% to 18.3% by weight of shell calcined calcium powder and 0.1% of citric acid powder in a step separate from the step of granulating the granules.
It is formed by mixing a powder mixture formed by mixing 2 wt% to 3.5 wt% with a mixed powder and compressing the mixture with a tableting machine.

Further, the content of calcium carbonate and the mixing ratio of citric acid in the calcined shell calcium are 1.0: 0.3.
1.0 to 1.0.

The mixing ratio between the granules and the mixed powder is as follows:
1.0: 0.05 to 1.0: 0.15.

[0018]

The present invention is constructed as described above. This time, the present inventors have repeatedly studied to improve the shortcomings of calcined shell calcium as a raw material of this excellent calcium supplement, and as a result, it was formulated as a foaming agent. Successfully improved the disadvantages of the prior art, compared to other natural calcium such as precipitated calcium carbonate and organic acid calcium, and other natural calcium such as bone meal. Could be effectively used as a raw material.

Hitherto, it has been widely and generally known that it is easy to use a foaming agent obtained by combining a sodium bicarbonate and an acid when producing a foaming agent, and has been applied in various fields. This is because, as shown in the following reaction formula, NaHCO ₃ baking soda is easily dissolved in water, and easily reacts with an acid to release carbon dioxide CO ₂ . NaHCO ₃ + H ⁺ → Na ⁺ + H ₂ O + C
O ₂ ↑

However, when baking soda is used as a foaming agent, sodium carbonate Na ₂ CO ₃ remains to make food alkaline, or hypertension, which has recently been found to be caused mainly by excessive intake of sodium Na, With the occurrence of diseases such as cerebrovascular diseases becoming a social problem, it is conceivable that ingesting unnecessary sodium may damage health.

The tablet of the present invention can be easily foamed without using a foaming agent such as baking soda. This is because calcium carbonate CaCO in the shell calcined calcium
₃ reacts citric acid C ₆ H ₈ O ₇ to generate carbon dioxide gas CO ₂ , thereby causing foaming. Due to the foaming, calcium reacted with citric acid is ionized in an aqueous solution, thereby facilitating absorption into the body.

[0022] In addition, due to the generation of carbon dioxide gas inside the tablet due to foaming, a calcium tablet containing shell calcined calcium as a main component is broken from the inside of the tablet by a physical effect and rapidly disintegrated in water, Fine particles. By the micronization, the contact area with the stomach acid in the stomach dramatically increases, the acid-alkali reaction in the stomach is promoted, and the calcium in the calcium tablet containing shell calcined calcium as a main component has the following chemical formula As shown in the reaction formula (1), it is completely ionized and absorbed into the body. Further, by using citric acid, among the organic acids used in foods, the equivalent required for neutralization with alkali is small, the safety is excellent, and the texture is good.

[0023]

Embedded image

This is effective not only for calcium supplementation and absorption in general healthy people, but also when the body function such as a child is in the growth process, and calcium supplementation and hypogastric acidity such as a person with gastrointestinal disease and an elderly person. Excellent effect for absorption.

Further, in order to produce the above-mentioned calcined calcium carbonate foam, water is not used in the production process, and anhydrous alcohol is used. This is because, when water is used, the calcium carbonate in the calcined shell calcium reacts with citric acid during the manufacturing process to release carbon dioxide gas. This is because foaming is no longer performed.

The content ratio (weight ratio) of the calcium carbonate content and the citric acid content in the raw material shell calcined calcium is in the range of 1.0: 0.3 to 1.0: 1.0. It is good to mix with. If the citric acid is blended at a lower ratio than the above ratio, foaming that is insufficient to disintegrate the tablet will not be performed. If citric acid is added more than the mixing ratio of calcium carbonate, it reacts with moisture in the air, raw materials, or tablets during storage, and foaming occurs. As a result, the tablet disintegrates, the hardness decreases, and the tablet becomes brittle.

Further, in the granulation step as a pre-step of tableting, when mixing and granulating calcined shell calcium and citric acid, the mixture is not divided into a single granule, but is divided into granules and a mixed powder.
At the time of tableting, the mixing ratio (weight ratio) is set to 1.0: 0.
It is advisable to mix and tablet within the range of from 0.05 to 1.0: 0.15. If the mixing ratio of the mixed powder is smaller than the above ratio, the reaction between calcium carbonate and citric acid is reduced, and foaming of carbon dioxide gas sufficient for disintegration of the tablet does not occur. On the other hand, if the mixing ratio of the mixed powder is higher than the above ratio, the powder is unsuitable for tableting, and reacts with moisture in the air, raw materials or tablets during storage, and foaming occurs. As a result, the tablet disintegrates, the hardness decreases, and the tablet becomes brittle.

[0028]

The present invention will be described in detail below with reference to Examples and Comparative Examples with reference to experimental examples of tablet production. Manufacturing Experiments Tablets having 51 patterns were manufactured by changing the mixing ratio of calcined shell calcium and citric acid and the mixing ratio of granules and powder, and each tablet was subjected to a disintegration test and a tablet stability test. In addition, an experiment on calcium absorbability was performed using one of the examples and the conventional tablet. In addition, the component ratio of the shell calcined calcium used as the raw material of this experiment is as follows. Calcium content 62.0 wt% Water content 0.5 wt% Ash content 9.3 wt% And the essence of this shell calcined calcium is a mixture of calcium carbonate (CaCO ₃ molecular weight 100.09) and calcium oxide (CaO molecular weight 56.08). If so, the following relational expression is approximately established between the amount of calcium (a) and the amount of calcium carbonate (b) in 100 g of calcined shell calcium.

[0029]

(Equation 1)

From the above component ratio, the amount of calcium in 100 g of calcined shell calcium is as follows: a = 100 g × 0.62 = 62 g. Then, from Equation 1, the shell calcined calcium 10
The amount of calcium carbonate in 0 g is b = 224.70−3.14 × 62 =
30.02 g. Therefore, the amount of calcium carbonate in the calcined shell used in the present production experiment is about 30 wt% of the total weight of the calcined shell. The formula and production method when 51 kinds of shell fired calcium agents were manufactured using the shell fired calcium as a raw material are shown below.

1. Formulation Table 1 below shows the mixing ratio of the raw material formulation amounts of the shell calcined calcium and citric acid and the mixing ratio of the granules (A granules) and the powder (B powder). Each formulation contains 1.
Tablets were prepared by adding 0 wt% of sucrose fatty acid esters. The sucrose fatty acid ester and citric acid used are those that have passed the official standards of food additives.

[0032]

[Table 1]

In Table 1 above, the value in parentheses indicates the amount (wt%) of calcium carbonate contained in the calcined shell calcium. This is because the content ratio of calcium carbonate in the calcined shell calcium is about 30 wt% as described above. For example, the weight of calcium carbonate in the raw material formulation of No. 21 to No. 30 is about 24.9 wt%. %. And, the mixing ratio (weight ratio) of the raw material prescription amount is assuming that the weight of calcium carbonate in the shell calcined calcium is 1.
It shows the weight ratio of citric acid. Therefore, the mixing ratio of citric acid with respect to the mixing ratio of calcium carbonate is calculated as 15.0 wt% ÷ 24.9 wt% ≒ 0.6.

The mixing ratio of A granule and B powder is
It shows the weight ratio of B powder to the total weight of granules and B powder. For example, the mixing ratio of the A granules and the B powder of No. 28 is 9.80 wt% ÷ (88.20 wt% + 9.80 wt%).
wt%) = 0.1.

Further, al in the table indicates whether or not anhydrous alcohol is used. ○ indicates that anhydrous alcohol was used during tablet production. And, X indicates that water was used without using anhydrous alcohol during tablet production. In addition, the formulation of No. 52 and the production method described below are:
It is close to the formulation and manufacturing method of conventional commercial calcium supplements.

2. Manufacturing Method Each of the 51 formulas shown in Table 1 is used to manufacture 51 types of foamed shell-calcined calcium agents. This manufacturing method is shown in FIGS. 1 and 2. FIG. 1 shows a production method using anhydrous alcohol when producing A granules, and FIG.
This is a production method when water is used when producing granules.

Hereinafter, a method for producing a tablet will be described in detail with reference to FIGS. (1) Manufacturing method in the case of using anhydrous alcohol As shown in FIG. 1, first, A granules and B powder are manufactured in different steps. The amounts and proportions shown in FIG. 1 and in the following text describe the No. 28 prescription as an example. For each of the other prescriptions, an experiment was performed according to the prescription in Table 1. (a) Manufacturing method of A granule 74.7% by weight of calcined shell calcium and citric acid 13.
5 wt% in anhydrous alcohol, respectively,
Mix both. The amount of the anhydrous alcohol is appropriately adjusted while observing the dissolved state of calcined shell calcium and citric acid. And if you mix well, this mixture,
After forming into granules by an extrusion type granulator having an opening of 0.8 mmφ, the granules are stored in a shelf dryer and dried at a temperature of 60 ° C. for 4 hours to produce A granules. (b) Production method of B powder Shell fired calcium 8.3 wt% and citric acid 1.5 w
and t% are mixed well in powder form to produce B powder.

(C) Tablet Compression Method 88.2 wt% of A granules and B powder produced as described above.
And 8 wt%. At the time of this mixing, 2.0 wt% of sucrose fatty acid ester is added together and mixed. This is blended as a release agent to make it easier to remove the tablet from the mold when the tablet is subsequently compressed. The mixture of the A granules and the B powder is tableted by a rotary tableting machine and processed into tablets. By this processing, one tablet 30
Produce tablets of 0 mg small triangular shape and hardness of 4 kg.

Here, the tablet hardness shown above is a value measured using a Kiya hardness meter. This Kiya type hardness meter is used for a hardness test based on the Japanese Pharmacopoeia, and indicates hardness by pressure (kg) applied to a pressing surface (diameter: 5 mm) of a tablet when the tablet is crushed. In the following, all items described as hardness indicate values measured with a Kiya hardness meter.

(2) Production method when water is used without using anhydrous alcohol As shown in FIG. 2, first, A granules and B powder are produced in separate steps. The amounts and proportions shown in FIG. 2 and in the following text describe the No. 23 prescription as an example. For each of the other prescriptions, an experiment was performed according to the prescription in Table 1. (a) Manufacturing method of A granule 74.7% by weight of calcined shell calcium and citric acid 13.
5 wt% in appropriate water, and both are mixed. Then, the mixture is opened at a diameter of 0.8 mmφ
The mixture is formed into granules by an extrusion granulator, and then stored in a shelf-type dryer and dried at a temperature of 60 ° C. for 8 hours to produce A granules. In an experimental example using anhydrous alcohol, A
The drying time of the granules is 4 hours.
Since water is used for the production, it is difficult to dry as compared with the case where anhydrous alcohol is used, so that the drying time is extended. (b) Manufacturing method of B powder B powder is manufactured by thoroughly mixing 8.3 wt% of calcined shell calcium powder and 1.5 wt% of citric acid powder. (c) Tablet compression method 88.2 wt% of A granules and B powder produced as described above.
And 8 wt%. At the time of this mixing, 2.0% by weight of sucrose fatty acid ester is also mixed together as a release agent. Then, similarly to (1), each tablet is processed into small triangular tablets of 300 mg and hardness of 4 kg using a rotary tableting machine.

5 prepared according to the above-described formulation and manufacturing method
One pattern of tablets was subjected to the following disintegration test and tablet stability test to determine its suitability as a calcined shell calcium agent.

Disintegration test Test Method and Judgment Criteria The Japanese Pharmacopoeia General Test Method "Disintegration Test Method" was applied mutatis mutandis, and the suitability was determined from the results as follows. First, using the device specified in the disintegration test method, six samples were taken for each of tablets No. 1 to No. 52, and
One sample is placed in each glass tube. Using water as the test solution, put an auxiliary board, move up and down,
Observe for a minute. When observing, for all six samples,
No residue is found in the glass tube, or if it is found, it is a spongy substance or it is deemed to have disintegrated when the soft substance is slight.

2. Test Results The results of the disintegration test are as shown in Table 2 below. ○ in the table indicates that the tablet foamed and the disintegration was extremely good. Moreover, x in a table | surface shows that a tablet did not foam at all or hardly foamed, and the disintegration of the tablet was not observed.

[0044]

[Table 2]

From the above results, it was found that N produced using water
o.1-No.5, No.11-No.15, No.21-No.25, N
With the tablets of the formulations o.31 to No.35 and No.41 to No.45, foaming was not observed immediately after the tablets were placed in the test solution. Further, even after 30 minutes from the start of the disintegration test, no disintegration of the sample was observed. This is because water was used in the production process, so that citric acid and calcium carbonate in the calcined shell calcium had already reacted during the production process, and carbon dioxide gas had been generated. Therefore, it is presumed that carbon dioxide was not generated even if the tablet was put in water, and therefore, foaming did not occur.

Further, at the same time as citric acid and calcium carbonate react during the manufacturing process, calcium oxide and water react to form an insoluble calcium hydroxide gel. It is considered that the water as the liquid did not penetrate and the disintegration property was extremely poor. Therefore, it has been found that it is difficult to produce a product having good foaming and disintegration in the production method using water.

In addition, in the tablets using anhydrous alcohol other than those described above, most of the formulation examples foamed vigorously immediately after being added to the test solution, and showed extremely good disintegration properties. By the way, while it was judged to be suitable, No. 16 to No. 18 were slightly foamed immediately after putting the tablet in the test solution,
After 5 minutes, it foamed very well and collapsed. But,
Even tablets using anhydrous alcohol, No. 51 (compounding ratio 0.0) and No. 6 to No.
In the formulation example of 10 (mixing ratio 0.15), foaming was not observed and was unsuitable. This is presumably because the mixing ratio of citric acid was small with respect to the content of calcium carbonate in the calcined shell calcium, so that the reaction was reduced and foaming sufficient for collapse did not occur.

However, in the formulation of No. 52, the compounding ratio of calcium carbonate and citric acid was 0.6, and even if it was manufactured using anhydrous alcohol, foaming did not occur and was unsuitable. . This is presumably because the mixing ratio of the A granules and the B powder was 0.0 and the B powder was not blended, so that the reaction was reduced and sufficient foaming for disintegration did not occur. Further, the formulation of No. 26 was also unsuitable, and it was presumed that no foaming occurred because the mixing ratio of B powder was 0.025, which was small. However, even if the blending ratio of the B powder is 0.025, No. 16, No. 36, No. 46
Has been determined to be conformable with active foaming. This is considered to be due to some errors due to various conditions, such as differences in temperature and humidity during tablet production and testing, differences between manufacturers and experimenters, even with the same mixing ratio. .

Tablet stability test Test Method and Criteria Each of the tablets No. 1 to No. 52 takes about 300 samples, puts them in a glass bottle, seals it, and stores it at room temperature. Every 15 days from the storage date, 10 samples are taken out of the container, the hardness is measured with a Kiya type hardness meter, the average value is determined, and this is defined as the hardness of the sample. By 60 days, if the hardness is 50% or more of the initial hardness, it is determined to be suitable. This is because the hardness of the tablet is usually stable with time, but the hardness may decrease due to moisture absorption or a change in content components. Usually, when the hardness is 1 kg or less, the tablet is brittle enough to be easily crushed by a finger.

2. Results The results of the tablet stability test performed on the calcined shell preparations prepared according to the formulations No. 1 to No. 52 are as follows.
The results are shown in Table 3 below.

[0051]

[Table 3]

From the test results shown in the above table, No. 3
With respect to Nos. 0, No. 40, and Nos. 46 to 50, as the number of days passed, the hardness decreased, the tablet disintegrated, and was judged to be unsuitable. The hardness of the other tablets did not change much, and the stability was good and the tablet was judged to be suitable.

No. 4 determined to be unsuitable from the above results
In Formulation Examples 6 to No. 50, the mixing ratio of citric acid was 1.5 in the mixing ratio of calcium carbonate and citric acid. Since the amount of citric acid is large in this way, the presence of moisture in the air, raw materials, or tablets causes the reaction between calcium carbonate and citric acid in baked husk calcium to generate carbon dioxide gas. Therefore, it is considered that the disintegration started from inside the tablet. However, even if the compounding ratio of citric acid is 1.5, it is determined that the formulation of No. 41 to No. 45 is suitable. Since these tablets were produced using water, citric acid and calcium carbonate react during production and carbon dioxide gas is generated and released as described in the disintegration test. At the time of the sex test, it is presumed that the reaction between calcium carbonate and citric acid did not occur and the tablet did not disintegrate.

The mixing ratio of the A granules and the B powder was not suitable for the No. 30, No. 40, and No. 50 formulation examples in which the mixing ratio of the B powder was 2.0. This is because if the mixing ratio of the powder is too high, it is difficult to harden and is not suitable for tableting, and the presence of moisture in the air, raw materials, or tablets causes the calcium carbonate in the shell calcined calcium to react with citric acid. It is thought that carbon dioxide was generated and the disintegration started from inside the tablet.

Comprehensive Judgment The results of the above tablet disintegration test and stability test were integrated to make a comprehensive judgment of tablet compatibility. Formulations that were determined to be compatible in both the disintegration test and the stability test were determined to be compatible in this overall determination. A prescription determined to be unsuitable in either test is determined to be unsuitable by the comprehensive evaluation. Table 4 shows the results of this determination.

[0056]

[Table 4]

From the above determination results, the mixing ratio (weight ratio) of the content of calcium carbonate in the calcined shell calcium to the raw material formulation of citric acid was 1.0: 0.3 to 1.0: 1.
0 and the mixing ratio (weight ratio) of A granule and B powder is 1.
If a tablet is formed from 0: 0.05 to 1.0: 0.15,
Tablets do not disintegrate, can be stored for a long time, and can be used stably in terms of quality. On the other hand, when taken, it is rapidly disintegrated in the mouth and stomach, and a tablet having good absorption in the body can be obtained.

When the mixing ratio of citric acid in the mixing ratio of the raw material formulation is less than 0.3, foaming sufficient to disintegrate the tablet may not be performed. If the mixing ratio of citric acid is more than 1.0, calcium carbonate and citric acid react with each other due to the presence of moisture in the air, raw materials, and tablets during storage, and foaming occurs. As a result, the tablet may disintegrate, reduce the hardness, and become brittle, which is unsuitable for long-term use.

When the mixing ratio of the B powder to the mixing ratio of the A granule and the B powder is less than 0.05, the reaction between calcium carbonate and citric acid is reduced, and foaming sufficient for disintegration does not occur. It may be something. On the other hand, if the mixing ratio of the B powder is more than 0.15, it is hard to be solidified and is not suitable for tableting, and calcium carbonate and citric acid are added during storage due to moisture in the air, raw materials, and tablets. Reacts to cause foaming. As a result, the stability of the tablet may be reduced, making it unsuitable for long-term use.

However, according to Table 4, even when the mixing ratio of the B powder was 0.025 or 0.2, No. 16, No. 36
And No. 20 are formulations suitable for tablets. However, this is limited to the case where the mixing ratio of citric acid in the raw material formulation amount is 0.3 or 1.0. Also, even if the compounding ratio of citric acid is 0.3 to 1.0, No. 26, No. 30, No.
A formulation of 40 is unsuitable. As described above, even when the mixing ratio and the mixing ratio are the same, the difference is caused in the determination result.
As described above, it is considered that the difference is caused by various conditions at the time of tablet production or at the time of testing, or by a difference in a combination of a mixing ratio and a mixing ratio.

Therefore, the mixing ratio between the content of calcium carbonate and the raw material formulation of citric acid is 1.0: 0.3 to 1.0:
1.0 and the mixing ratio of A granules and B powder is 1.0: 0.0
When it is in the range of 5 to 1.0: 0.15, it is possible to reliably produce a high-quality calcium supplement which can be used for a long period of time and has excellent absorption power.

As described above, in the production experiment of 51 patterns,
No. 16 to No. 20, No. 27 to No. 29, No. 36 to No. 3
9 is a successful formulation example, which is an example of the present invention. Also,
No.1 to No.15, No.21 to No.26, No.30 to No.3
5, No. 40 to No. 52 are comparative examples with respect to the embodiment.

From the formulas in the examples, A granules and B
Calculate the minimum and maximum weight of calcined shell calcium and citric acid in the powder. First, the minimum / maximum mixing ratio of the raw material prescription amount and the minimum / maximum mixing ratio of the A granules and the B powder in the mixing ratio are picked up. The results are shown in the remarks of Table 4. No. 1 shown in these remarks
Table 5 below shows the respective blending ratios and mixing ratios of Nos. 6, No. 20, No. 36, and No. 39.

[0064]

[Table 5]

The mixing ratio of the raw material formulation in Table 5 above is the weight ratio of the calcined shell calcium, citric acid and the release agent to the total weight of wt%, and the mixing ratio of A granules and B granules is also It shows the weight ratio wt% to the total weight of the B powder and the release agent. Therefore, when the total of the calcined shell calcium and the citric acid was 100 wt% except for the release agent, it was converted into the weight of the calcined shell and citric acid in each of the A granules and the B powder. Table 6 shows the calculation results.

[0066]

[Table 6]

The method of calculating the numerical values shown in Table 6 is shown below. A, a ', b, b' in the calculation formula are calculated by substituting the mixing ratio and the mixing ratio corresponding to each prescription with reference to Table 5. (1) Weight wt% of calcined shell calcium in A granules (combination ratio of calcined shell a with respect to the whole raw material a ÷ 98.0) × (combination ratio of A granule a ′ ÷ 98.0) × 100 = axa (÷) 96.04 (wt%) (2) Weight wt% of citric acid in A granules (blending ratio of citric acid to the whole raw material b ÷ 98.0) × (blending ratio of A granules a '' 98.0 ) × 100 = b × a ′ ÷ 96.04 (wt%) (3) Weight wt% of calcined shell calcium in B granules (mixing ratio of calcined shell calcium to the entire raw material a ÷ 98.0) × (B granules 100% a × b ′ ÷ 96.04 (wt%) (4) Weight wt% of citric acid in B granules (mixing ratio of citric acid to the whole raw material b ÷ 98 .0) × (B granule blending ratio b ′ ÷ 98.0) × 100 = b × b ′ ÷ 96.04 (wt%)

The minimum and maximum weights of calcined shell calcium and citric acid in A granules and B powder are shown in the margins of Table 6. Therefore, calcined shell calcium 65.4 wt% -8
9.4 wt% and citric acid 6.6 wt% to 22.5 wt%
Is granulated with anhydrous alcohol to form granules, and in a step separate from the granulation step of the granules, shell calcined calcium powder 2.0 wt% to 18.3 wt% and citric acid powder 0.2 w
The calcium supplement of the present invention can be produced by mixing t% to 3.5 wt% to form a mixed powder, and mixing the mixed powder with the granules.

In addition to the above weight range, the mixing ratio of the calcium carbonate content to the raw material formulation of citric acid is 1.0: 0.3 to 1.0: 1.0, If the calcium supplement is manufactured in a mixing ratio of 1.0: 0.05 to 1.0: 0.15, it becomes possible to obtain a product which can be stored for a long period of time and has excellent absorbability.

Experiment on Absorbability of Calcium Using the tablet of one example of the experiment described above and the tablet of the conventional example, an experiment on the in vivo absorbability of the foamed baked shell calcium agent was performed. 1. 2. Samples (1) Test sample A calcined calcium carbonate shell of No. 28, which is one of the examples, is used. (2) Control sample A non-foamed shell-calcined calcium agent of No. 52, which is a conventional example, is used. As described above, when mixing and granulating calcined shell calcium and citric acid, a tablet is produced using only granules without mixing powder. This production method is similar to the formulation and production method of conventional commercial calcium supplements.

2. Preparation of sample solution The total calcium content (calcium carbonate + calcium oxide) of each of the test sample and the control sample was determined in advance. The total calcium content in one tablet (300 mg) is: 300 mg × 0.83 × 0.62 = 154.
4 mg. Next, each sample was pulverized, and a sample (about 200 mg of tablets) corresponding to 100 mg of the total calcium content in each sample was added to 100 ml of a 0.5% sodium carboxymethylcellulose solution. The solution was stirred so as to be turbid, and this solution was used as each sample solution.

3. Experimental method Wister rats weighing about 160 g were used and fasted for 18 hours, and only water was supplied. Physiological saline was loaded simultaneously with the oral administration of 2 ml (2 mg as calcium) of each sample solution so that the total applied volume was 2.5 v / wt% of body weight. Rats are placed one by one in the metabolism gauge,
The urine excreted by 5 hours was collected, and the amount of calcium in the urine was determined by a titration method using disodium ethylenediaminetetratetraacetate (indicator NN reagent). The number of experimental animals was 6 in each group, during which only water was supplied.

4. Results Table 7 below shows the results of determining the absorbability of the test sample and the control sample in the calcium in rats by the above-mentioned experimental method.

[0074]

[Table 7]

Calcium once absorbed in the body is rapidly excreted in urine due to ion balance as a body function of excreting excess electrolyte outside the body. On the other hand, calcium not absorbed into the body is excreted in feces. Therefore, by measuring the amount of calcium in urine, the amount of calcium absorbed in the body can be determined. Since 2 mg of calcium has been administered as a sample in advance, the dose ratio of the test sample is calculated as 1.56 mg ÷ 2 mg = 78.0%. The dose ratio of the control sample is calculated as 0.42 mg / 2 mg = 21.0%. As a result of this experiment, in the test sample, that is, in the rat absorption experiment of calcium agent No. 28 of one example of the present invention, a control sample, that is, a conventional calcium supplement
3.7 times that of No. 52 (78.0 %％ 21.0
%). These results also show that the calcium agent of the present invention is a high-quality calcium supplement having excellent absorption power.

Use Example Since the calcined foamed shell preparation of the present invention has a good calcium absorbability as described above, if it is produced by this production method, in addition to the calcined shell and citric acid, a sweetener and a pigment Even if fragrances, vitamins and the like are added, a foamed shell-calcined calcium supplement having good absorbability can be produced. For this reason, it becomes a calcium supplement food excellent in power calcium absorption and taste. The following is a prescription of the use example.

[0077]

In the above formulation, the raw materials other than calcined shell calcium and citric acid are soluble. Therefore, when the tablet is taken, it is rapidly dissolved and diffused in the mouth and stomach to prevent disintegration of the tablet. Absent. However, if the specific gravity of these raw materials is too large, the amount of the powder may be too large to be suitable for tableting. In addition, dissolution takes time, and the amount of carbon dioxide generated is small, so that there is a possibility that good disintegration of the tablet may not be performed. Further, since the tablet has a small absolute amount of calcium, it does not fulfill the purpose as a drug. It is preferable to appropriately determine the amount of each raw material in consideration of such a problem.

[0079]

According to the present invention having the above-described structure, foaming can be easily performed without using a blowing agent such as baking soda. Due to this foaming, carbon dioxide gas is generated inside the tablet, and due to the physical effect, the tablet is broken from the inside of the tablet and disintegrates quickly in water,
Since the particles are formed into fine particles, the contact area with the gastric acid in the stomach is dramatically increased, and the acid-alkali reaction in the stomach is promoted. Therefore, the calcium in the tablet is completely ionized and can be efficiently absorbed in the body. Further, by using citric acid, irritation and discomfort at the time of ingestion can be prevented, and a calcium supplement excellent in safety and good in texture can be produced.

[Brief description of the drawings]

FIG. 1 is a flowchart showing a manufacturing process of an embodiment for manufacturing a calcium supplement using anhydrous alcohol.

FIG. 2 is a flowchart showing a production process of a comparative example in which a calcium supplement is produced using water.

Claims (3)

[Claims] 1. A calcined shell calcium of 65.4% by weight to 8%.
9.4 wt% and citric acid 6.6 wt% to 22.5 wt%
And granules formed with anhydrous alcohol, and in a step separate from the granulation step of the granules, shell calcined calcium powder 2.0 wt% to 18.3 wt% and citric acid powder 0.2
A calcium supplement, which is formed by mixing a powder mixture formed by mixing the powder with an amount of 0.5% by weight to 3.5% by weight and compressing the mixture with a tableting machine. 2. The content of calcium carbonate and the mixing ratio of citric acid in the calcined shell calcium are 1.0: 0.3 to 0.3:
2. The calcium supplement according to claim 1, wherein the ratio is 1.0: 1.0. 3. The mixing ratio between the granules and the mixed powder is as follows:
2. The calcium supplement according to claim 1, wherein 0: 0.05 to 1.0: 0.15.