WO2015020191A1

WO2015020191A1 - Calcium agent

Info

Publication number: WO2015020191A1
Application number: PCT/JP2014/071005
Authority: WO
Inventors: 俊夫藤村; 和田　実
Original assignee: 日東薬品工業株式会社
Priority date: 2013-08-09
Filing date: 2014-08-08
Publication date: 2015-02-12
Also published as: JP6554034B2; JPWO2015020191A1

Abstract

Provided is a calcium agent that is easily ingested and has superior flavor, disintegration properties in the mouth, and the like. The calcium agent has superior flavor, disintegration properties in the mouth, and the like by means of adding a disintegration agent and/or an organic acid or the like to a calcium salt and a magnesium salt.

Description

Calcium preparation

The present invention relates to a chewable tablet which is a calcium agent and includes calcium salt and magnesium salt, a disintegrant and / or an organic acid, etc., and has excellent flavor and disintegration in the mouth.

Calcium is an essential mineral for living organisms, and various products such as pharmaceuticals containing calcium, health foods, and nutritional supplements are commercially available to supplement calcium (Patent Documents 1 and 2).
In conventional commercial products, for example, calcium supplementation for women in pregnancy and lactation, calcium reinforcement for relieving irritations due to osteoporosis and calcium deficiency, calcium supplementation for children in the growing period, etc. have been frequently taken.

On the other hand, in the face of an aging society, elderly people need more calcium intake to prevent osteoporosis and the like. In order to make it easier for elderly people to take calcium, the pharmaceutical and food industries have widely adopted the use of tablets and capsules. However, problems such as difficulty in swallowing and the tendency to increase the number of tablets to be taken as aged can occur, so it is possible to take even elderly people by making chewable tablets such as chewable tablets rather than capsules. Ingenuity has been made to make it easier. However, even with chewable tablets, calcium preparations have a powdery feeling due to calcium carbonate, which is an active ingredient, and are difficult to take for people with weak chewing ability. There is a problem with the disintegration within. In terms of storage management, the shape of the tablet is preferable, and it is desired to solve the above problems while maintaining the necessary hardness as a tablet.

Japanese Patent Laid-Open No. 08-059486 JP 2010-187595 A

An object of the present invention is to provide a calcium agent (chewable tablet) that is excellent in flavor and disintegration in the mouth and is easy to take.

As a result of intensive studies in view of the above-mentioned problems, the inventors of the present invention contain a calcium salt and a magnesium salt, and further include a calcium agent containing a specific type of disintegrant, a calcium agent containing an organic acid, or a disintegration. In the calcium agent which mix | blended the agent and the organic acid, it discovered that flavor, disintegration, etc. improved dramatically, and came to complete this invention.

That is, the present invention is as follows:
[1] A calcium agent comprising a calcium salt and a magnesium salt, and further comprising a disintegrant.
[2] A calcium agent containing a calcium salt and a magnesium salt, and further containing an organic acid.
[3] A calcium agent comprising a calcium salt and a magnesium salt, and further containing a disintegrant and an organic acid.
[4] Disintegrant is carboxymethyl starch sodium, carmellose, carmellose calcium, carmellose sodium, hydrous silicon dioxide, agar powder, croscarmellose sodium, crospovidone, light anhydrous silicic acid, crystalline cellulose, synthetic aluminum silicate, Alpha starch, partially pregelatinized starch, wheat starch, rice starch, corn starch, potato starch, dioctyl sodium sulfosuccinate, low substituted sodium carboxymethyl starch, low substituted hydroxypropyl cellulose, hydroxyethyl methyl cellulose, dextrin, tragacanth Powder, lactose hydrate, hydroxypropyl starch, D-mannitol, magnesium aluminate metasilicate, and purified agar for disintegration Calcium agent according to at least one member [1] or [3].
[5] The calcium agent according to [1] or [3], wherein the disintegrant is low-substituted hydroxypropylcellulose or crospovidone.
[6] The organic acid is at least one selected from the group consisting of citric acid, malic acid, tartaric acid, gluconic acid, succinic acid, malonic acid, maleic acid, fumaric acid and ascorbic acid [2] or [3 ] Calcium agent as described in.
[7] The calcium agent according to [2] or [3], wherein the organic acid is at least one selected from the group consisting of citric acid, malic acid, tartaric acid, gluconic acid, succinic acid, and fumaric acid.
[8] Calcium salt is calcium carbonate, calcium lactate, calcium silicate, calcium chloride, calcium hydroxide, calcium phosphate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate dihydrate, calcium dihydrogen phosphate monohydrate, glucone Calcium according to any one of [1] to [7], which is at least one selected from the group consisting of calcium oxide, calcium glycerophosphate, calcium citrate, calcium L-aspartate, dolomite, borei powder and purified bovine bone meal Agent.
[9] The calcium agent according to any one of [1] to [8], wherein the calcium salt is calcium carbonate.
[10] The magnesium salt is at least one selected from the group consisting of magnesium carbonate, magnesium oxide, magnesium chloride, magnesium sulfate, magnesium hydroxide, magnesium aluminate silicate and organic acid magnesium [1] to [9 ] The calcium agent in any one of.
[11] The calcium agent according to any one of [1] to [10], wherein the magnesium salt is magnesium carbonate.
[12] The calcium agent according to any one of [1] to [11], containing 10 to 90% by mass of a calcium salt based on the total amount of the calcium agent.
[13] The calcium agent according to any one of [1] to [12], containing 1 to 20% by mass of a magnesium salt based on the total amount of the calcium agent.
[14] The calcium agent according to any one of [1], [3] to [5], and [8] to [11], containing 0.1 to 30% by mass of a disintegrant based on the total amount of calcium agent.
[15] The calcium agent according to any one of [2], [3], and [6] to [11], containing an organic acid in an amount of 0.01 to 50% by mass based on the total amount of the calcium agent.
[16] The calcium agent according to any one of [1] and [3] to [11], containing 0.5 to 10% by mass of a disintegrant and 0.03 to 5% by mass of an organic acid based on the total amount of the calcium agent.
[17] The calcium agent according to any one of [1] to [16], wherein the calcium agent is a chewable tablet.
[18] The calcium agent according to any one of [1] to [17], which is used as a medicine or food.
[19] The calcium agent according to any one of [1] to [17], which is used as a pharmaceutical product.
[20] The calcium preparation according to [19], wherein the pharmaceutical is a combination with natural vitamin D3.
[21] Chewable tablets containing calcium salt and magnesium salt whose disintegration time is within 15 minutes.
[22] The chewable tablet according to [21], having a hardness of 2 to 20 kp.
[23] Chewable tablets comprising the following (A) and (B):
(A) granules containing calcium and magnesium salts;
(B) A tableting aid containing at least one selected from the group consisting of a disintegrant and an organic acid.

According to the present invention, by providing a calcium agent with better flavor and disintegration in the mouth, it becomes easy for even elderly people to take calcium agent, and to obtain improved compliance in continuous administration Can do. In addition, it becomes easy to take, and even a child can take continuous calcium supplements.

Details of the present invention will be described below. The present invention provides a calcium agent containing a calcium salt and a magnesium salt and a disintegrating agent, a calcium salt and a magnesium salt and an organic acid, or a calcium salt and a magnesium salt, and a disintegrating agent and an organic acid.

The calcium preparation of the present invention contains calcium and magnesium, and is supplemented with calcium in osteoporosis, the growth period, pregnancy / lactation period, etc., and a RANKL inhibitor that is a calcium / natural vitamin D3 / magnesium compound ( It has uses such as treatment and prevention of hypocalcemia associated with administration of denosumab (genetical recombination).

The calcium salt used in the present invention is calcium carbonate, calcium lactate, calcium silicate, calcium gluconate, calcium chloride, calcium hydroxide, calcium phosphate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate dihydrate, dihydrogen phosphate. Examples include, but are not limited to, calcium monohydrate, calcium glycerophosphate, calcium citrate, calcium L-aspartate, calcium alginate, water-soluble calcium salt, and the like. In addition, as another embodiment, a calcium complex containing a calcium salt such as calcium-EDTA, dolomite, borei powder, and purified beef bone meal can be used.
Of these, calcium carbonate, calcium lactate, calcium gluconate, calcium hydrogen phosphate dihydrate and the like are preferable.
More preferably, it is calcium carbonate. As calcium carbonate, various polymorphs such as calcite, aragonite, vaterite, and amorphous (amorphous) can also be used. More preferably, it is precipitated calcium carbonate.

The content of the calcium salt in the calcium agent of the present invention is 10 to 90% by mass, preferably 20 to 85% by mass, particularly preferably 30 to 80% by mass, based on the total amount of the calcium agent.

Examples of the magnesium salt used in the present invention include magnesium carbonate, magnesium oxide, magnesium chloride, magnesium sulfate, magnesium hydroxide, magnesium silicate aluminate, organic acid magnesium (magnesium lactate, magnesium gluconate, etc.), etc. It is not limited to.
Preferably, magnesium carbonate, magnesium oxide, magnesium hydroxide, etc. are mentioned, More preferably, magnesium carbonate is mentioned.
Magnesium is mainly stored in the vicinity of the bone surface as magnesium ions. When metabolism is insufficient, calcium ions are replaced and magnesium is replenished into the body. Magnesium is involved in calcium metabolism.

The content of the magnesium salt in the calcium agent of the present invention is 1 to 20% by mass, preferably 2 to 15% by mass, particularly preferably 3 to 10% by mass, based on the total amount of the calcium agent.

Disintegrants used in the present invention include croscarmellose sodium, carmellose calcium, carmellose, carmellose sodium, celluloses such as low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, low-substituted carboxymethyl starch sodium, Carboxymethyl starch, hydroxypropyl starch, pregelatinized starch, partially pregelatinized starch, wheat starch, rice starch, corn starch, potato starch, etc., hydrous silicon dioxide, agar powder, crospovidone, light anhydrous silicic acid, crystalline cellulose Synthetic aluminum silicate, dioctyl sodium sulfosuccinate, hydroxyethyl methyl cellulose, dextrin, tragacanth powder, lactose hydrate, D- N'nitoru, magnesium aluminometasilicate, although breakdown purified agar, and the like, without limitation. Preferred are low-substituted hydroxypropylcellulose (L-HPC), crospovidone, croscarmellose sodium and the like listed in the Japanese Pharmacopoeia. More preferred are L-HPC and crospovidone. These can use a commercial item suitably.

The content of the disintegrant in the calcium agent of the present invention is 0.1 to 30% by mass, preferably 0.2 to 20% by mass, particularly preferably 0.3 to 10% by mass, based on the total amount of the calcium agent.

Examples of the organic acid used in the present invention include, but are not limited to, monocarboxylic acids having 6 or less carbon atoms, dicarboxylic acids, trivalent or higher polyvalent carboxylic acids, hydroxycarboxylic acids, and carboxylic anhydrides. Examples of hydroxycarboxylic acids include citric acid, malic acid, DL-malic acid, tartaric acid, gluconic acid, succinic acid, malonic acid, glutaric acid, maleic acid, fumaric acid, glutaconic acid, ascorbic acid, and the like. It is not limited. Moreover, the mixture of 1 or more types of these may be sufficient. Preferably, malic acid, DL-malic acid, tartaric acid, gluconic acid, succinic acid, malonic acid, maleic acid, fumaric acid, citric acid, ascorbic acid and the like, more preferably malic acid, DL-malic acid, tartaric acid , Succinic acid, fumaric acid and citric acid, particularly preferably DL-malic acid and citric acid.

The content of the organic acid in the calcium agent of the present invention is 0.01 to 50% by mass, preferably 0.02 to 30% by mass, particularly preferably 0.03 to 20% by mass, based on the total amount of the calcium agent.

The dosage and frequency of administration of the calcium preparation of the present invention depends on the age, weight, health status, sex, degree of medical condition or combination of drugs being taken, or other factors if treatment is being performed. Can be determined. For example, about 10 to 150 mg / kg (body weight) per day, preferably about 20 to 100 mg / kg (body weight), more preferably 30 to 60 mg / kg (body weight) 1 to 4 times, more preferably Can be taken once or twice.
More specifically, per day, calcium as 1-20 mg / kg (body weight), preferably 5-15 mg / kg (body weight), and magnesium as 0.05-1 mg / kg (body weight), preferably 0.25-0.75 mg. / Kg (body weight) can be taken.

The calcium preparation of the present invention may contain other components described later, for example, nutrients such as minerals and vitamins, drugs and additives, but is not limited thereto.

Examples of minerals include, but are not limited to, zinc and selenium.

Examples of vitamins include, but are not limited to, vitamin B (B1, B2, B3, B5, B6, etc.), vitamin C, vitamin D (D2, D3, D4, D5, etc.), vitamin K, and the like. Vitamin D is preferable, and vitamin D3 (cholecalciferol) is more preferable. As vitamins, commercially available products can be used. For example, commercially available products (such as RIKEN DRY D3-B5N-GP) can be used for vitamin D3. It does not matter whether it is natural or synthetic. Natural vitamins are preferred.

Additives include, but are not limited to, excipients, binders, colorants, flavoring agents, lubricants, and the like. In addition, preservatives, color formers, fragrances, stabilizers, acidulants and the like that are generally used in foods can also be added. Examples thereof include ethyl vanillin, vanillin, glycerin fatty acid ester, medium chain fatty acid triglyceride and the like. These additives are used in amounts conventionally used in the technical field of pharmaceutical preparations. These additives may be used by mixing two or more kinds at an appropriate ratio.

Examples of excipients include, but are not limited to, maltitol, maltol, erythritol, D-mannitol, D-sorbitol, xylitol, purified sucrose, sucrose, fructose, glucose, powdered reduced maltose syrup, and lactose.

Examples of the binder include, but are not limited to, hydroxypropyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone, pullulan, macrogol, gum arabic, gum arabic powder, and gelatin.

Examples of the colorant include, but are not limited to, one or more components selected from edible pigments such as edible yellow No. 5, edible red No. 2, and edible blue No. 2, edible lake pigments, and iron sesquioxide. .

Any flavoring agent may be used as long as it is used as a sweetener, a refreshing agent, a fragrance or the like. For example, yogurt flavor, vanilla flavor, aspartame, amateur powder, saccharin, caramel, cinnamon powder, dipotassium glycyrrhizinate, stevia, mint oil, orange oil, lemon oil, pine oil, 1-menthol, fruit flavor, chocolate flavor, etc. For example, but not limited to. More preferably, a yogurt flavor is mentioned.

Lubricants include, but are not limited to, magnesium stearate, calcium stearate, talc, sodium lauryl sulfate, light anhydrous silicic acid, hydrous silicon dioxide, sucrose fatty acid ester and the like. More preferred are magnesium stearate and talc.

The calcium preparation of the present invention can be taken in combination with a drug. The drug can be appropriately determined according to the health condition, sex, degree of medical condition, etc. of the subject. Examples of the drug include, but are not limited to, vitamins, RANKL inhibitors (such as denosumab), and citric acid agents.

Examples of the dosage form of the calcium preparation of the present invention include tablets, chewable tablets and the like, and chewable tablets are preferred.

The calcium agent of the present invention is excellent in disintegration in the mouth, and can be disintegrated, for example, in 0.5 to 30 minutes, preferably in several minutes (eg, 1 to 2 minutes). The calcium agent chewable tablets of the invention can disintegrate within 15 minutes, preferably within 10 minutes, more preferably within 2 minutes.
The disintegration time can be measured according to the method for operating an immediate release preparation according to the 16th revised Japanese Pharmacopoeia disintegration test method.

The hardness when the calcium agent of the present invention is made into a chewable tablet is 2 to 20 kp, preferably 3 to 15 kp, more preferably 4 to 10 kp in terms of storage management. The hardness is measured by a commonly used tablet hardness measuring device, for example, a tablet hardness tester manufactured by Schleuniger. Such desired hardness can be obtained by compression pressure at the time of tableting and preparation of components. If the hardness is lower than this range, damage tends to occur during the manufacturing, packaging, distribution process, and the like, and if it is higher, it tends to be difficult to chew.

The tablet in the present invention can be obtained using a general granulation method. That is, after sufficiently mixing the above calcium salt, excipient, and other additives as necessary, granulation is performed using a lower alcohol such as ethanol or isopropanol, or water that may contain the lower alcohol. After drying, sizing as necessary, tableting is performed with a tableting machine to form tablets. Alternatively, the mixed powder can be compressed into tablets by a direct compression method. As an example, it will be described in the following examples, but is not limited to this method.

Examples of the apparatus used for granulation include, but are not limited to, a vertical granulator, a high shear mixer, a high speed mixer, a planetary mixer, and the like.

Another embodiment of the present invention includes a chewable tablet comprising the following (A) and (B):
(A) granules containing calcium and magnesium salts;
(B) A tableting aid containing a disintegrant or an organic acid or a mixture thereof.
Specific examples of the (A) calcium salt and magnesium salt are the same as described above, and the content in the chewable tablet is also the same as the above definition.
In the present specification, the “tableting aid” means a component mixed with the granules of (A) before the tableting step in the production of chewable tablets. The tableting aid (B) may contain one or more of the specific disintegrant and organic acid described above.
The tableting aid (B) contains additives conventionally used in the pharmaceutical field. As this additive, the above-mentioned further additive etc. are mentioned, for example. These additives are used in conventional amounts in the pharmaceutical field unless otherwise specified. The tableting aid (B) may contain two or more of these additives in an appropriate ratio.

The content of the disintegrant contained in the tableting aid (B) in the chewable tablet of the present invention is usually 0.1 to 30% by mass, preferably 0.2 to 20% by mass, more preferably 0.3 to 10% by mass.

The content of the organic acid contained in the tableting aid (B) in the chewable tablet of the present invention is usually 0.01 to 50% by mass, preferably 0.02 to 30% by mass, more preferably 0.03 to It is 20% by mass, particularly preferably 0.1 to 10% by mass, most preferably 0.3 to 5% by mass.

The weight of the chewable tablet of the present invention is not particularly limited, but is 200 to 2000 mg, preferably 300 to 1500 mg per tablet.

The following are mentioned as a suitable specific example of the chewable tablet in this invention.
Chewable tablets containing the following (a) and (b):
(A) calcium salt (preferably calcium carbonate, calcium lactate, calcium gluconate, calcium hydrogen phosphate dihydrate) and magnesium salt (preferably magnesium carbonate, magnesium oxide, magnesium hydroxide); excipient (preferably Sucrose, gelatin, sorbitol, mannitol) and binder (preferably polyvinylpyrrolidone); and optionally stabilizers (preferably glycerin fatty acid esters), emulsifiers (preferably medium chain fatty acid triglycerides, lauric acid) Granules consisting of sorbitan);
(B) a disintegrant (preferably low-substituted hydroxypropylcellulose (L-HPC), crospovidone, croscarmellose sodium, or a mixture thereof), an organic acid (preferably malic acid, DL-malic acid, tartaric acid, A tableting aid comprising fumaric acid, citric acid, ascorbic acid or a mixture thereof) and a lubricant (preferably magnesium stearate).

As a preferred specific example, the chewable tablet (A) can be produced according to the following production process.

(1) Granule (A) can be produced by, for example, mixing calcium salt and magnesium salt together with additives and granulating this mixture. More specifically, a solvent dispersion of a binder is added and granulated. The product is then dried and the resulting granulated product is crushed to obtain a sized powder.
(2) A tableting aid (B) is added to the granulated powder and mixed to obtain granules for tableting.
(3) The granules are tableted with a tableting machine to obtain uncoated tablets.

The calcium preparation of the present invention can be applied to pharmaceuticals (medical drugs or over-the-counter drugs), foods, and the like.

As mentioned above, the drug includes osteoporosis, developmental period, calcium supplementation in pregnancy, lactation, etc., and calcium / natural vitamin D3 / magnesium combination agent (RANKL inhibitor (denosumab (genetical recombination) etc.) However, it is not limited to these, but the use such as treatment and prevention of hypocalcemia associated with administration is included, but it is not limited thereto.

Examples of foods include, but are not limited to, health foods, nutritional supplements (supplements), foods for specified health use, and the like.

Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

Reference example Precipitated calcium carbonate 6,100g, magnesium carbonate 473.6g, sucrose powder 1,885.2g was mixed using a high-speed mixer (FS-GS-25 manufactured by Earth Technica) and then using a flow coater (Freund Sangyo FlO-5A). Granulate and dry while adding 184 g of polyvinylpyrrolidone dissolved in 1,042 g of purified water, and use a power mill (P-3S made by Showa Kagaku Kikai) and a circular vibratory sieve (TM-40-2S made by Deoksugakusho). And sized to obtain a sized powder. Add sized powder 864.28g, vitamin D3 (RIKEN) 32g, magnesium stearate 4.4g, yogurt flavor 1.15g, mix, and compress with rotary tableting machine (HT-AP15SS-II, manufactured by Hata Seiko) 1 tablet of 1,127 mg was produced. The tablet hardness averaged 7.37 kp.

When disintegrating agent is added 864.28 g of the sized powder prepared in Reference Example and 18.4 g of low-substituted hydroxypropylcellulose, 32 g of vitamin D3 (RIKEN), 4.4 g of magnesium stearate and 1.15 g of yogurt flavor as a disintegrating agent Then, it was compressed with a rotary tableting machine (HT-AP15SS-II type, manufactured by Hata Seiko Co., Ltd.) to produce 1 tablet of 1,150 mg. Tablet hardness was 7.81 kp on average, and sufficient hardness as a tablet (chewable tablet) was obtained.

When disintegrating agent is added 864.28 g of the sized powder prepared in Reference Example and 46 g of low-substituted hydroxypropylcellulose, 32 g of vitamin D3 (RIKEN), 4.4 g of magnesium stearate, and 1.15 g of yogurt flavor as a disintegrating agent are mixed. The tablet was compressed with a rotary tableting machine (HT-AP15SS-II type, manufactured by Hata Seiko Co., Ltd.) to produce 1185 mg tablet. Tablet hardness was 7.15 kp on average, and sufficient hardness as a tablet (chewable tablet) was obtained.

When disintegrating agent is added 864.28 g of the sized powder prepared in Reference Example and 46 g of crospovidone, 32 g of vitamin D3 (RIKEN), 4.4 g of magnesium stearate and 1.15 g of yogurt flavor as a disintegrating agent are added and mixed. The tablet was compressed with a tablet machine (HT-AP15SS-II, manufactured by Hata Seiko Co., Ltd.) to produce 1 tablet of 1,185 mg. Tablet hardness was 7.16 kp on average, and sufficient hardness as a tablet (chewable tablet) was obtained.

When organic acid is added 864.28 g of the sized powder prepared in Reference Example and DL-malic acid 18.4 g as organic acid, vitamin D3 (RIKEN) 32 g, magnesium stearate 4.4 g, yogurt flavor 1.15 g, and mixed, The tablet was compressed with a rotary tableting machine (HT-AP15SS-II, manufactured by Hata Seiko), and 1 tablet of 1,150 mg was produced. Tablet hardness was 8.36 kp on average, and sufficient hardness as a tablet (chewable tablet) was obtained.

When organic acid is added 864.28 g of the sized powder prepared in Reference Example and 46 g of DL-malic acid, 32 g of vitamin D3 (RIKEN), 4.4 g of magnesium stearate and 1.15 g of yogurt flavor as organic acids are added and mixed. The tablet was compressed with a type tableting machine (HT-AP15SS-II, manufactured by Hata Seiko Co., Ltd.) to produce 1185 mg tablet. Tablet hardness was 7.5 kp on average, and sufficient hardness as a tablet (chewable tablet) was obtained.

When organic acid is added 864.28 g of the sized powder prepared in the Reference Example and 18.4 g of tartaric acid, 32 g of vitamin D3 (RIKEN), 4.4 g of magnesium stearate, and 1.15 g of yogurt flavor as organic acids are added and mixed. The tablet was compressed with a tablet machine (HT-AP15SS-II, manufactured by Hata Seiko Co., Ltd.) to produce 1 tablet of 1,150 mg. Tablet hardness was 7.81 kp on average, and sufficient hardness as a tablet (chewable tablet) was obtained.

When organic acid is added 864.28g of the sized powder prepared in the Reference Example and 18.4g of succinic acid, 32g of vitamin D3 (RIKEN), 4.4g of magnesium stearate, and 1.15g of yogurt flavor as organic acids are added and mixed. Rotary type The tablet was compressed with a tableting machine (HT-AP15SS-II, manufactured by Hata Seiko Co., Ltd.) to produce 1 tablet of 1,150 mg. The tablet hardness averaged 7.09 kp, and sufficient hardness as a tablet (chewable tablet) was obtained.

When organic acid is added 864.28g of the sized powder prepared in Reference Example and 18.4g of fumaric acid, 32g of vitamin D3 (RIKEN), 4.4g of magnesium stearate and 1.15g of yogurt flavor as organic acids are added and mixed. Rotary type The tablet was compressed with a tableting machine (HT-AP15SS-II, manufactured by Hata Seiko Co., Ltd.) to produce 1 tablet of 1,150 mg. Tablet hardness was 7.15 kp on average, and sufficient hardness as a tablet (chewable tablet) was obtained.

In case of adding disintegrant and organic acid 864.28g sized powder prepared in Reference Example, 18.4g crospovidone as disintegrant, 18.4g malic acid as organic acid, 32g vitamin D3 (RIKEN), 4.4g magnesium stearate, yogurt Fragrance 1.15 g was added and mixed, and compressed with a rotary tableting machine (HT-AP15SS-II type, manufactured by Hata Seiko Co., Ltd.) to produce 1,173 mg tablets. Tablet hardness was 8.83 kp on average, and sufficient hardness as a tablet (chewable tablet) was obtained.

In case of adding disintegrant and organic acid 864.28g sized powder prepared in Reference Example, 18.4g crospovidone as disintegrant, 18.4g citric acid as organic acid, 32g vitamin D3 (RIKEN), 4.4g magnesium stearate, yogurt Fragrance 1.15 g was added and mixed, and compressed with a rotary tableting machine (HT-AP15SS-II type, manufactured by Hata Seiko Co., Ltd.) to produce 1,173 mg tablets. Tablet hardness was 8.4 kp on average, and sufficient hardness as a tablet (chewable tablet) was obtained.

Experimental example 1
The tablets produced in Reference Examples and Examples 1 to 10 were subjected to a disintegration test according to the 16th revised Japanese Pharmacopoeia General Test Method Disintegration Test Method operating method for immediate release preparations. Water was used as the test solution. Do not use auxiliary panels. The results are shown in Table 1.

Compared with the reference example, the disintegration time was significantly shortened in Examples 1 to 3 to which a disintegrant was added. Also in Examples 4 to 8 in which an organic acid was added, the disintegration time was significantly shortened compared to the reference example. In particular, in the example in which the disintegrant and the organic acid were added, the disintegration time was about 2 minutes, and the result was very short.

The present invention relates to a calcium agent containing calcium salt and magnesium salt as active ingredients, for disintegrating agents, organic acids, etc., for problems such as powderiness of calcium salt and improvement of dosage for the elderly with weak biting power, etc. It has been clarified that the addition of can improve the disintegration as well as the feeling of administration, resulting in a more soluble calcium preparation. By this invention, it becomes possible to improve the compliance of the subject who takes a calcium agent. The calcium agent of the present invention can be applied to various fields such as pharmaceuticals and foods, and the present invention is extremely useful industrially.

This application is based on Japanese Patent Application Nos. 2013-166857 and 2013-189790 filed in Japan, the contents of which are incorporated in full herein.

Claims

A calcium agent characterized by including a calcium salt and a magnesium salt and further containing a disintegrant.
A calcium agent characterized by containing a calcium salt and a magnesium salt and further containing an organic acid.
A calcium agent characterized by containing a calcium salt and a magnesium salt, and further containing a disintegrant and an organic acid.
Disintegrants are sodium carboxymethyl starch, carmellose, carmellose calcium, carmellose sodium, hydrous silicon dioxide, agar powder, croscarmellose sodium, crospovidone, light anhydrous silicic acid, crystalline cellulose, synthetic aluminum silicate, pregelatinized starch , Partially pregelatinized starch, wheat starch, rice starch, corn starch, potato starch, dioctyl sodium sulfosuccinate, low substituted sodium carboxymethyl starch, low substituted hydroxypropyl cellulose, hydroxyethyl methylcellulose, dextrin, tragacanth powder, lactose From the group consisting of hydrate, hydroxypropyl starch, D-mannitol, magnesium aluminate metasilicate and purified agar for disintegration Calcium agent according to claim 1 or 3 is at least one-option.
The calcium agent according to claim 1 or 3, wherein the disintegrant is low-substituted hydroxypropylcellulose or crospovidone.
The organic acid is at least one selected from the group consisting of citric acid, malic acid, tartaric acid, gluconic acid, succinic acid, malonic acid, maleic acid, fumaric acid and ascorbic acid. The calcium agent according to item.
The calcium agent according to any one of claims 2 to 5, wherein the organic acid is at least one selected from the group consisting of citric acid, malic acid, tartaric acid, succinic acid, and fumaric acid.
Calcium salt is calcium carbonate, calcium lactate, calcium silicate, calcium chloride, calcium hydroxide, calcium phosphate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate dihydrate, calcium dihydrogen phosphate monohydrate, calcium gluconate, The calcium preparation according to any one of claims 1 to 7, which is at least one selected from the group consisting of calcium glycerophosphate, calcium citrate, calcium L-aspartate, dolomite, borei powder, and purified bovine bone meal.
The calcium agent according to any one of claims 1 to 8, wherein the calcium salt is calcium carbonate.
The magnesium salt is at least one selected from the group consisting of magnesium carbonate, magnesium oxide, magnesium chloride, magnesium sulfate, magnesium hydroxide, magnesium aluminate silicate and organic acid magnesium. The calcium agent according to item.
The calcium agent according to any one of claims 1 to 10, wherein the magnesium salt is magnesium carbonate.
The calcium preparation according to any one of claims 1 to 11, comprising 10 to 90 mass% of calcium salt based on the total amount of calcium preparation.
The calcium agent according to any one of claims 1 to 12, comprising 1 to 20% by mass of a magnesium salt based on the total amount of the calcium agent.
The calcium agent according to any one of claims 1 and 3 to 13, wherein the disintegrant is contained in an amount of 0.1 to 30% by mass based on the total amount of the calcium agent.
The calcium agent according to any one of claims 2 to 14, comprising an organic acid in an amount of 0.01 to 50% by mass based on the total amount of the calcium agent.
The calcium agent according to any one of claims 1 and 3 to 13, comprising 0.5 to 10% by mass of a disintegrant and 0.03 to 5% by mass of an organic acid based on the total amount of the calcium agent.
The calcium preparation according to any one of claims 1 to 16, wherein the calcium preparation is a chewable tablet.
The calcium preparation according to any one of claims 1 to 17, which is used as a medicine or food.
The calcium preparation according to any one of claims 1 to 17, which is used as a pharmaceutical product.
The calcium preparation according to claim 19, wherein the pharmaceutical is a combination preparation with natural vitamin D3.