JP2009209058A - Calcium preparation for promoting osteogenesis - Google Patents

Abstract

A calcium preparation for promoting bone formation that can sufficiently promote bone formation is provided.
A calcium preparation for promoting bone formation, comprising calcium carbonate having an average particle size of 0.05 to 0.1 μm.
[Selection] Figure 1

Description

  The present invention relates to a calcium preparation for promoting bone formation.

  Osteoporosis is a bone aging disease in which bone density decreases and bones become brittle. Osteoporosis is a particularly problematic issue in today's aging society because it increases the risk of femoral neck fractures and spinal compression fractures in daily life, and causes so-called bedridden elderly people. In order to prevent such osteoporosis, it is considered to be effective to promote bone formation by sufficiently ingesting foods and supplements containing calcium.

  However, since the absorption rate into the living body with respect to the intake amount of calcium is limited, the effect of promoting bone formation cannot be sufficiently obtained simply by taking calcium. Thus, several methods have been proposed for improving calcium absorption and promoting bone formation by processing the ingested calcium into fine particles.

  For example, crushed and washed oyster shells, scallop shells, abalone shells or corals are kept at a temperature below the collapse temperature of the organic skeleton structure of each of these shells or corals and dried uniformly. A method of producing an active absorption type calcium powder characterized by milling with a cylindrical centrifugal fluidized crusher showing a formula operation (refer to Patent Document 1), and fine powder of cuttlefish bone or shell to a particle size classification average value of 70 μm or less Calcium powder (see Patent Document 2), which is made into a main material, calcium powder comprising particles having a particle size of 20 to 650 nm and (major axis / minor axis) of 1.5 or less (see Patent Document 3) ), Etc. have been proposed.

  However, these methods are not always satisfactory, and there is a demand for a calcium preparation for promoting bone formation that can further promote bone formation.

JP-A-5-155775 JP-A-8-59486 JP 2007-332062 A

  An object of the present invention is to provide a calcium preparation for promoting bone formation that can sufficiently promote bone formation.

  As a result of intensive studies to solve the above-mentioned problems, the present inventor can solve the above-mentioned problems by refining the calcium carbonate powder and setting the average particle diameter within the range of 0.05 to 0.1 μm. The present invention was completed based on the findings.

  That is, this invention consists of the calcium formulation for bone formation promotion characterized by containing calcium carbonate with an average particle diameter of 0.05-0.1 micrometer.

  The calcium preparation for promoting bone formation of the present invention is particularly useful for promoting an increase in the amount of bone tissue calcium.

  The production method of the calcium preparation for promoting bone formation of the present invention is not particularly limited, and a method known per se can be used. Below, the manufacturing method of the preferable calcium formulation for osteogenesis is illustrated. For example, glycerin diacetyl tartaric acid fatty acid ester is added to water and stirred and dissolved at about 45 to 75 ° C. Calcium carbonate powder is added to the obtained solution to prepare a slurry containing calcium carbonate powder, and the slurry is pulverized by a wet pulverizer as an object to be pulverized. An excipient such as dextrin is added and dispersed in a pulverized slurry containing calcium carbonate refined by pulverization, and the resulting dispersion is dried to obtain a calcium preparation for promoting bone formation.

  The calcium carbonate powder used as a raw material for the calcium preparation for promoting bone formation of the present invention is not particularly limited as long as it can be used as a food. For example, it is a calcium carbonate powder derived from scallop shells, and has an average particle size. Of 1.0 to 100 μm is preferably used. As such calcium carbonate powder, for example, Livical H-1 (manufactured by Riken Vitamin Co., Ltd.) is commercially produced and sold, and can be used in the present invention.

  The contents of calcium carbonate powder, glycerin diacetyl tartaric acid fatty acid ester and water in 100% by mass of the slurry containing calcium carbonate powder are not particularly limited. For example, calcium carbonate powder is usually about 10 to 30% by mass, glycerin diacetyl tartaric acid. It is preferable to adjust so that fatty acid ester may be about 0.1-1.0 mass% normally, and the remainder may be water. Further, for the purpose of adjusting the viscosity of the slurry or adjusting the pH, an appropriate amount of anhydrous citric acid, trisodium citrate or the like may be added to the slurry.

  The wet pulverizer is for finely pulverizing the slurry to be pulverized using glass beads, zirconia beads, etc. filled in the pulverization chamber as a dispersion medium. For example, DYNO-MILL MULTI LAB (manufactured by Willy et Bacofen), MINICER (Manufactured by Ashizawa Finetech), sand mill (manufactured by Shinto Kogyo Co., Ltd.), bead mill (manufactured by Finetech) or the like, and these can be used in a one-pass system or a circulation system. As a dispersion medium used in the wet pulverizer, beads made of zirconia, alumina, titania, silicon nitride, steel, glass, or the like can be used. Among these, zirconia beads are preferable from the viewpoint of durability and wear resistance.

  The apparatus for dispersing the excipient is not particularly limited, and for example, a normal stirring / mixing tank equipped with a stirrer, a heating jacket, a baffle plate, and the like can be used. As the stirrer to be equipped, for example, a high-speed rotary dispersing / emulsifying machine such as TK homomixer (manufactured by Primix) or Claremix (manufactured by Mtechnics) is preferably used. As the operating conditions of the dispersing / emulsifying machine, for example, in a small laboratory machine, a rotation speed of about 2000 to 20000 rpm and a stirring time of about 5 to 60 minutes can be exemplified.

  Examples of the method for drying the dispersion include spray drying, drum drying, belt drying, vacuum drying, and vacuum freeze drying, and spray drying is preferable. There is no restriction | limiting in particular as a spray-drying apparatus, Well-known apparatuses, such as a spray-type spray-drying apparatus or a rotary disk-type spray-drying apparatus, can be used. In addition, as operating conditions for spray drying, for example, the dispersion is supplied to a pressure nozzle type spray drying apparatus, hot air inlet temperature is about 120 to 200 ° C, preferably about 140 to 190 ° C, exhaust temperature is about 70 to 140 ° C, Preferably, the calcium preparation for promoting bone formation can be obtained by spray drying under conditions of about 85 to 100 ° C. and collecting the dried product with a cyclone.

  The average particle diameter of calcium carbonate contained in the calcium preparation for promoting bone formation of the present invention is preferably about 0.05 to 0.1 μm, more preferably about 0.06 to 0.09 μm. When the average particle diameter exceeds 0.1 μm, the effect of promoting bone formation cannot be obtained sufficiently, which is not preferable. On the other hand, when the average particle size is 0.05 μm or less, the calcium carbonate particles are aggregated and the dispersed state cannot be maintained, which is not preferable.

  An example of a preferred embodiment of the calcium preparation for promoting bone formation according to the present invention is that calcium carbonate is about 4-70% by mass, preferably about 10-50% by mass, excipient (eg, dextrin) in 100% by mass of the formulation. Etc.) about 20 to 95% by mass, preferably about 40 to 80% by mass, and glycerin diacetyltartaric acid fatty acid ester about 0.01 to 5.0% by mass, preferably about 0.1 to 1.0% by mass. It is a powder.

  Since the calcium preparation for promoting bone formation of the present invention has an action of promoting bone formation as shown in the following test examples, it can be expected to have a high effect on the treatment or prevention of osteoporosis. Further, the calcium preparation for promoting bone formation of the present invention is highly safe and can be used by adding to foods and beverages without any limitation.

  When the calcium preparation for promoting bone formation of the present invention is used by adding it to foods and beverages, there is no particular limitation on these forms, for example, beverages such as juice, coffee and the like to which conventional food additives are added in addition to the preparations, Liquid foods such as soup, milky or pasty foods such as milk and curry, semi-solid foods such as jelly and gummy, solid foods such as gum, tofu and supplements, or powdered foods, margarine, mayonnaise, dressing, etc. Examples include oils and fats-containing foods.

  Further, the calcium preparation for promoting bone formation of the present invention itself can be taken orally as an oral composition. Examples of oral compositions include tablets, granules, fine granules, pills, powders, capsules (including hard capsules and soft capsules), troches, chewables, and liquids (drinks). Can be mentioned.

  When ingesting the osteogenesis promoting preparation of the present invention or a food or drink to which the preparation is added, the daily dose of adult calcium carbonate (body weight 60 kg) as an active ingredient is not particularly limited. The range is 0.01 to 100 g, preferably about 0.05 to 10 g. This dose may be taken in one dose or divided into several doses.

  Hereinafter, the present invention will be described more specifically based on examples and test examples, but the present invention is not limited to these examples.

[Example]
In a 5000 ml stainless steel container, 1516 ml of water and 4 g of glycerin diacetyltartaric acid fatty acid ester (trade name: Poem W-70; manufactured by Riken Vitamin Co., Ltd.) are placed and stirred in a warm water bath at 70 ° C. (Three One Motor FBL-600: HEIDON, The mixture was stirred and dissolved at 500 rpm for about 5 minutes using a 5-cm diameter 4-blade type stirring blade 1 stage. 400 g of calcium carbonate powder (trade name: Libical H-1; manufactured by Riken Vitamin Co., Ltd.) and 40 g of trisodium citrate are added to the obtained solution, and the mixture is stirred at 500 rpm for about 5 minutes using the stirrer in a 70 ° C. hot water bath. -Dispersed to obtain a dispersion. To the obtained dispersion, 10 g of anhydrous citric acid was added little by little, and the mixture was stirred and dispersed with a stirrer at 500 rpm for about 5 minutes in a warm water bath at 70 ° C. Furthermore, microcrystalline cellulose (trade name: Theola SC as a dispersion aid) -900; manufactured by Asahi Kasei Chemicals Corporation) was added and stirred and dispersed in a warm water bath at 70 ° C. for about 5 minutes at 500 rpm using the stirrer to prepare 2000 g of a slurry containing calcium carbonate. It was pH 7.24 as a result of measuring the liquid property of the obtained slurry using the pH meter.

  The slurry is supplied to a wet pulverizer (device name: DYNO-MILL MULTI LAB; manufactured by Willy et Bacofen; zirconia media having a particle size of 0.65 mm), a peripheral speed of 14.0 m / sec, a flow rate of 360 cc / Under the condition of min, the first pulverization process was performed by the one-pass method, and 900 g of pulverized slurry was obtained.

  The pulverized slurry obtained by the first pulverization treatment is supplied to a wet pulverizer (device name: MINICER; manufactured by Ashizawa Finetech; using zirconia media having a particle diameter of 0.30 mm), and the peripheral speed is 12.0 m / sec. The second pulverization treatment was performed by a circulation method (10 circulation cycles) under the condition of a flow rate of 200 cc / min to obtain 600 g of a pulverized slurry.

  148.7 g of dextrin (trade name: Paindex # 2; manufactured by Matsutani Chemical Co., Ltd.) is added as an excipient to 600 g of the pulverized slurry obtained by the second pulverization treatment, and a TK homomixer (TK HOMOMIXER MARK) is added. After stirring and dispersing at 10000 rpm for 10 minutes using II; manufactured by Primix Co., Ltd., dried and powdered with a spray dryer (model: L-8i type; manufactured by Okawara Chemical Co., Ltd.) at an inlet temperature of 180 ° C. and an exhaust temperature of 90 ° C. To obtain 176 g of a calcium preparation for promoting bone formation (practical product).

[Comparative example]
A slurry containing calcium carbonate powder was prepared in the same manner as in the above example, and the slurry was dried and powdered in the same manner as in the example without pulverizing to obtain 290 g of a calcium preparation for promoting bone formation (comparative product).

[Particle size analysis of calcium preparation for promoting bone formation]
The particle size analysis of the bone formation promoting calcium preparations (practical product and comparative product) obtained in the above examples and comparative examples was performed by laser diffraction method using HOLIBA LA-950 (product name; manufactured by Horiba, Ltd.). . The resulting particle size distribution graphs of the practical product and the comparative product are shown in FIGS. 1 and 2, respectively. In addition, since the scale of the vertical axis indicating the mass frequency (%) of the particles is different between the graphs of FIG. 1 and FIG. 2, the area of the entire peak of the particle size distribution is apparently different between the product of the implementation and the comparison product. There is no difference between the two methods of particle size analysis.

  Subsequently, based on the obtained particle size distribution, average particle sizes of the implementation product and the comparative product were obtained. Specifically, the mass frequency of the particle size distribution was integrated from the smaller particle size, and the particle size (particle size) at which the integrated value was 50% was taken as the average particle size. The results are shown in Table 1.

[Test example of bone formation promoting effect]
Below, the test example of the bone formation promotion effect by the calcium formulation for bone formation promotion of this invention is demonstrated.

<Test method>
The bone formation promoting calcium preparations (practical product and comparative product) obtained in the above examples and comparative examples were each suspended in purified distilled water to prepare suspensions having a calcium carbonate content of 6 mg / ml. 15 test rats (5 weeks old; male) growing up were randomly assigned to Group A (n = 5), Group B (n = 5) and Group C (n = 5). The administration group, group B were the comparative product administration group, and group C was the control group. Suspensions corresponding to the product in the A group, suspensions corresponding to the comparative product in the B group, purified distilled water as the control in the C group, and once a day for each test rat (dose : 1 ml of the above suspension per 100 g of test rat body weight) and orally administered for 14 days. Twenty-four hours after the final administration, the bone tissue calcium amount (mg / g) was measured for each group.

<Method for measuring bone tissue calcium>
The femur was removed from the rat and its muscle tissue was removed to obtain a bone tissue. The bone tissue was transferred to a 0.25M sucrose solution at about 10 ° C., bone marrow was removed from the bone tissue in the solution, and the bone tissue was further separated into those at the diaphysis and metaphysis. The obtained bone tissue of the diaphyseal part and metaphyseal end part was dried on a petri dish in a dryer at 80 ° C. for 8 hours, and the weight of the dried bone tissue was measured. The dried bone tissue was placed in a test tube, concentrated nitric acid was added thereto, and the mixture was thermally decomposed at 120 ° C. for about 16 hours. The resulting solution was used as a calcium measurement sample. The calcium weight in this calcium measurement sample was measured using a calcium measurement kit (product name: Calcium Test Wako; manufactured by Wako Pure Chemical Industries, Ltd.), the measured calcium weight (mg), and the weight of the dried bone tissue. Based on (g) and the following mathematical formula, the bone tissue calcium amount (mg / g) was calculated.

<result>
Aggregate bone tissue and metaphyseal bone tissue calcium levels (mg / g) in the administration product group and the control product administration group, and calculate the average value and standard error of the bone tissue calcium content of 5 test rats in each group. did. The results are shown in Table 2.
As a result of performing a paired t-test based on the aggregated data of each group, a significant difference was observed in the following four groups.
Implementation product administration group (diaphysis) vs. comparison product administration group (diaphysis): Risk rate 1%
Implementation product administration group (diaphysis) vs comparative product administration group (diaphysis): Risk rate 1%
Implementation product administration group (diaphysis) vs. control group (diaphysis): Risk rate 1%
Executed product administration group (diaphysis) vs control group (diaphysis): Risk rate 1%
This result shows that the calcium preparation for promoting bone formation of the present invention is particularly useful for promoting an increase in the amount of bone tissue calcium.

Graph showing the particle size distribution of calcium preparations for promoting bone formation (practical product) Graph showing the particle size distribution of calcium preparation for bone formation promotion (comparative product)

Claims (1)

  A calcium preparation for promoting bone formation, comprising calcium carbonate having an average particle size of 0.05 to 0.1 μm.

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