JPH10290682A - Calcium complex - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a calcium-phosphopeptide complex soluble in a neutral aqueous solution and excellent in absorbability and bioavailability, and to provide a method for producing the complex. SOLUTION: This complex is composed of phosphoprotein (phosphopeptide) and a casein-bindable calcium (colloidal calcium) obtained by adding an acid to casein-micelle to be <=pH5.4 and removing the casein. The complex is obtained by adding 0.5 to 10-fold wt. phosphoprotein (phosphopeptide) to a suspension of casein-bindable calcium (colloidal calcium) so as to adjust the resultant liquid to be >=pH5.5, then condensing it through a demineralizing process using membrane treatment or powdering it through a drying process. The complex is utilized as a calcium-enriching agent or as an additive to food and drink or feedstuff.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel calcium complex for enhancing calcium and a method for producing the same. Furthermore, the present invention relates to the use of such a complex as a calcium agent or the use as a calcium-enhancing drug, food or drink or feed. The calcium complex of the present invention has the characteristics of being excellent in the absorption and utilization of calcium in vivo, and has the characteristics of being water-soluble and having good solubility at neutral pH. As a highly available calcium agent, it can be added to various foods and drinks to enhance calcium.

[0002]

2. Description of the Related Art In recent years, with the aging of the population, osteoporosis,
The number of people suffering from various bone diseases such as fractures or back pain tends to increase. It is said that this is caused by insufficient intake of calcium, decreased ability to absorb calcium, or imbalance of hormones after menopause. It is said that in order to prevent such bone diseases associated with aging, it is necessary to consume as much as possible calcium with good absorbability in the living body in all stages of life from growth to senility. ing. However, it is said that it is extremely difficult to consume a sufficient amount of calcium in the average Japanese eating habits, and the intake of calcium in Japan is shown in the Ministry of Health and Welfare's National Nutrition Survey. In addition, it has been flat for the past 20 years and has not met the required amount.

[0003] Under such circumstances, various attempts have been made to increase the calcium intake as much as possible. For example, calcium salts such as calcium carbonate, calcium phosphate, calcium lactate, calcium gluconate, bovine bone, eggshell, etc. , A calcium agent containing natural calcium purified from coral, sea urchin shell or the like as an active ingredient, or calcium derived from milk, etc .; I have. The above-mentioned calcium carbonate, calcium phosphate, calcium lactate, calcium salts such as calcium gluconate and bovine bones, eggshell, coral, sea urchin shells, etc., natural calcium or milk-derived calcium, etc.
Although it is inferior in absorbability and utility in vivo, it has the advantage of being inexpensive and available in large quantities. In addition, it has been reported that calcium derived from milk is particularly excellent in absorption and utilization in vivo (Japanese Journal of Nutrition and Food Science, vol.43, pp.437-443, 1990; Applied Pharmacology, vol.
42, pp.245-253, 1991). In addition, casein-binding calcium and colloidal calcium, which are said to account for about 70% of milk-derived calcium, are superior to other milk-derived calcium in absorbability and utilization in vivo. (Nutr. Rep. Int., Vol. 21,
p.6738, 1980).

Further, the present inventors have proposed a milk-derived calcium agent containing casein-binding calcium and colloidal calcium as active ingredients (Japanese Patent Application Laid-Open No. 6-125740). They also reported that they are particularly excellent in in vivo use (Journal of Japan Society of Nutrition and Food Science, vol. 47, pp. 385-390, 1994).

However, further studies have shown that milk-derived calcium preparations containing casein-binding calcium and colloidal calcium as active ingredients include calcium salts such as calcium carbonate, calcium phosphate, calcium lactate, and calcium gluconate, and cattle. Compared to natural calcium etc. purified from bones, eggshells, corals, sea urchin shells, etc., it has the characteristic of being superior in absorbability and utilization in vivo, but water-insoluble calcium at neutral pH. Thus, it was found that absorption and utilization in the living body were inferior to calcium intake in the form of milk. That is, since the pH of the small intestine, which is the central site of calcium absorption in the living body, is in a neutral range, a milk-derived calcium agent containing casein-binding calcium and colloidal calcium as active ingredients forms a water-insoluble calcium salt. As a result, the absorption efficiency is lower than when calcium is taken in the form of milk.

A milk-derived calcium preparation containing casein-binding calcium and colloidal calcium as active ingredients is powdered by spray-drying or freeze-drying for the purpose of enhancing the storage stability. However, milk-derived calcium preparations containing powdered casein-binding calcium and colloidal calcium as active ingredients have poor solubility at neutral pH, and this calcium preparation is incorporated into various beverages and drinks. In this case, there is a problem that the calcium floats on the liquid surface, and precipitation occurs even when the calcium is dispersed by forced stirring or the like.

[0007]

DISCLOSURE OF THE INVENTION The present inventors have sought a calcium agent having high bioavailability which can be added to foods and drinks and the like. Disadvantages of calcium-derived calcium preparations containing calcium and colloidal calcium as active ingredients,
Intensive research has been conducted to solve the problems of water insolubility and poor powder solubility at neutral pH.

As a result, the casein-binding calcium and / or colloidal calcium is added to a solution containing casein-binding calcium and / or colloidal calcium under a certain pH condition and mixed with phosphoprotein and / or phosphopeptide. It has been found that calcium forms a complex with phosphoproteins and / or phosphopeptides. The calcium complex is water-soluble even in the neutral pH range, has good solubility even when powdered, and has high absorption and utilization in the living body. And found to be very excellent as a calcium agent to be incorporated into feeds and the like, and completed the present invention.

Accordingly, it is an object of the present invention to provide a novel calcium complex which is water-soluble at a neutral pH and has good solubility even as a powder, and a method for producing the same.
Further, the present invention provides a calcium agent containing the calcium complex having such properties as an active ingredient or a pharmaceutical, food, beverage or feed in which calcium is enhanced by blending a calcium complex having such properties. As an issue.

[0010]

SUMMARY OF THE INVENTION The present invention relates to a calcium complex in which casein-binding calcium and / or colloidal calcium forms a complex with phosphoprotein and / or phosphopeptide (hereinafter referred to as calcium complex). There is). This calcium complex can be obtained by, for example, adding a phosphoprotein and / or a phosphopeptide to a solution containing casein-binding calcium and / or colloidal calcium, mixing the mixture, and adjusting the pH to 5.5 or more. Therefore, the present invention relates to a solution containing casein-binding calcium and / or colloidal calcium, to which phosphoprotein and / or phosphopeptide is added and mixed, and the pH is adjusted to 5.5 or more to adjust the casein-binding calcium and / or colloidal calcium. The present invention relates to a method for producing a calcium complex, which forms a complex between calcium phosphate and phosphoprotein and / or phosphopeptide. Since the calcium complex produced by such a method is usually in a liquid state, it may be subjected to membrane treatment and desalting and concentration, or may be freeze-dried or spray-dried to be powdered. Further, the present invention relates to a calcium agent containing such a calcium complex as an active ingredient, and a calcium-enhanced drug, food, drink or feed containing such a calcium complex.

In mammals such as cow's milk, goat's milk, buffalo milk and sheep's milk, calcium is calcium phosphate-
It exists in the form of a casein complex or a calcium phosphate-citrate-casein complex or the like, or in the form of colloidal calcium phosphate existing between casein micelles. Therefore, in the present invention, calcium capable of binding to casein such as a calcium phosphate-casein complex or a calcium phosphate-citrate-casein complex is referred to as casein-binding calcium, and colloidal calcium phosphate is referred to as colloidal calcium.

The casein-binding calcium and colloidal calcium can be obtained by the following treatment. First, casein micelles are prepared from milk of mammals such as milk, goat milk, buffalo milk, and sheep milk. For example, when rennet casein is prepared as casein micelles, an appropriate amount of rennet is added to skim milk having a pH of 5.5 or more according to a conventional method to coagulate the milk, and then cut finely with a card knife. Next, warm the cut card and let it stand,
Eliminate whey. Then, water is added to the curd and the mixture is stirred for several minutes. After the curd is washed, the operation of leaving it still and excluding water is performed two to three times to obtain rennet casein. Further, for example, when preparing casein in which lactose and soluble minerals have been removed as casein micelles, according to a conventional method, whole milk or skim milk having a pH of 5.5 or more is subjected to an ultrafiltration membrane (fraction molecular weight of 50,000 Da or more), a microfiltration membrane, or the like. By treating with a membrane such as a reverse osmosis membrane or by performing electrodialysis, casein from which lactose and soluble minerals have been removed is obtained. The casein micelle thus prepared contains casein-binding calcium and colloidal calcium.

Next, the casein micelle thus prepared is adjusted to a pH of 5.4 or less by adding an acid thereto, and the casein is removed, thereby separating casein-binding calcium and colloidal calcium from the casein micelle and recovering the same. I do. That is, an inorganic acid such as hydrochloric acid and an organic acid such as acetic acid, lactic acid, and citric acid are added to the casein micelle to adjust the pH to 5.4 or less. At this time, using a homomixer, a colloid mill, or the like, sufficient agitation, kneading, milling, etc. are performed to prevent the formation of aggregates and to uniformly disperse the acid.

When an acid is added to the casein micelle, the pH becomes 5.4.
In the vicinity, colloidal calcium first dissociates. When the pH is gradually lowered to 5.1 or lower, calcium bound to casein is cleaved, and at pH around 4.8, calcium is completely dissociated from casein. Therefore, when it is desired to separately separate and recover casein-binding calcium and colloidal calcium, the casein-binding calcium and colloidal calcium are separated and recovered by utilizing the dissociation effect due to the above-described difference in pH. can do.

When the casein-binding calcium and the colloidal calcium are to be separated and recovered together, the pH is adjusted to 4.8 or less, and after vigorous dispersion treatment using a high-speed stirrer or the like, By allowing to stand, casein-binding calcium and colloidal calcium are separated from the casein micelles, and casein precipitates while remaining insoluble in water.Therefore, by collecting only the supernatant, casein-binding calcium and colloidal calcium are easily collected. Can be separated and recovered.

Furthermore, by treating with an ultrafiltration membrane, casein-binding calcium and colloidal calcium can be separated and recovered from casein micelles. That is, the acid is added to the casein micelle to adjust the pH to 5.4 or less, and the solution that has been homogenized by stirring is treated with an ultrafiltration membrane (molecular weight cut-off 50,000 Da or less), so that casein-binding calcium and colloidal Calcium can be separated and recovered on the permeate side. The casein-binding calcium and colloidal calcium obtained by the treatment with the ultrafiltration membrane contain anions such as chloride ions, so that the anions are removed by treatment such as electrodialysis to reduce the calcium content. Good to raise.

On the other hand, in the present invention, a protein containing an amino acid having a phosphate group is called a phosphoprotein, and a peptide containing an amino acid having a phosphate group is called a phosphopeptide. And, in the present invention, as a phosphoprotein, a protein containing an amino acid having a phosphate group prepared from casein in milk of mammals such as milk, goat milk, buffalo milk, and sheep milk can be used, Phosvitin, a protein derived from egg yolk, can also be used. Further, as the phosphopeptide, a peptide obtained by hydrolyzing the above phosphoprotein with a protease such as trypsin or the like can be used. In addition, proteins and peptides containing an amino acid having a phosphate group, such as phosphoserine, phosphothreonine, and phosphohistidine, or their degradation products can also be used.

Next, a method for preparing a phosphopeptide from casein in milk will be exemplified. That is, as described above, when preparing casein-binding calcium and colloidal calcium, the acid casein obtained as a precipitate is suspended in water, the pH is adjusted to 6.0 to 9.0, and then, based on the weight of casein. Add 0.001-2% trypsin, 15-60 ℃
And incubate for about 5 minutes to 100 hours. Thereafter, the pH is adjusted to about 4.6 by adding an inorganic acid such as hydrochloric acid or an organic acid such as acetic acid, lactic acid or citric acid, and the precipitate is separated by a decanter or the like, and the supernatant is collected. Then, about 2.0% of calcium chloride and about 5 times the amount of ethanol are added to the collected supernatant, mixed, centrifuged, and the precipitate is collected to obtain a high-purity phosphopeptide. . Also, a method for preparing phosphopeptides from casein micelles proposed by Ono et al. (Biosci. Biotech. Biochem., Vol.5).
8, pp. 1376-1380, 1994; Biosci. Biotech. Biochem.,
vol.59, pp.510-511, 1995). As phosphopeptides usable in the present invention, Meiji CPP (manufactured by Meiji Seika), CCP (manufactured by Taiyo Kagaku) and the like are commercially available.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION A calcium complex in which the casein-binding calcium and / or colloidal calcium of the present invention forms a complex with phosphoprotein and / or phosphopeptide is, for example, casein-binding calcium and / or phosphopeptide. A solution in which colloidal calcium is suspended is added with about 0.5 to 10 times the amount of phosphoprotein and / or phosphopeptide with respect to the calcium contained in the solution, mixed well, and then adjusted to pH 5.5 or more. Obtainable.

The calcium complex has a cross-linked structure of casein-binding calcium or colloidal calcium and phosphoprotein or phosphopeptide via a phosphate group of an amino acid having a phosphate group contained in the phosphoprotein or phosphopeptide. Are obtained by forming The casein-binding calcium and / or colloidal calcium and the phosphoprotein and / or the phosphopeptide form a complex in the calcium complex, and the molar ratio of calcium, inorganic phosphorus and organic phosphorus is 6 to 4. : 2 to 1: 1.

The calcium complex of the present invention can be used as a concentrate obtained by treating it with an evaporator or an ultrafiltration membrane, or can be obtained by spray-drying or freeze-drying, if necessary. It may be used as a powder. By treating with a membrane such as an ultrafiltration membrane or a microfiltration membrane, monovalent ions can be removed, free casein-binding calcium or colloidal calcium that does not form a calcium complex, or Since proteins and phosphopeptides can be removed, a calcium complex with higher purity can be obtained.

The calcium complex of the present invention can be used as it is as a calcium agent having good absorbability and availability in vivo. In addition, the calcium complex of the present invention can be used as a medicine suitable for oral administration of tablets, granules, liquids, etc., and also as a food or drink such as milk drink, cheese, juice, jelly, bread, noodles, soup, sausage, etc. It can be blended or further blended with a feed such as a feed additive, a blended feed, or a pet food.

Although the daily calcium requirement for Japanese adults is 600 mg, the current calcium intake is
It is about 550mg. Therefore, in order to compensate for the insufficient intake of calcium, in the case of an adult, the calcium complex of the present invention should be consumed at least 1 g (about 100 mg as calcium) per day, preferably at least 5 g (about 500 mg as calcium) per day. Is desirable.

Next, the present invention will be described in more detail with reference to Examples and Test Examples.

Reference Example 1 Raw milk was centrifuged to prepare skim milk, and rennet was added to the skim milk to prepare rennet casein. To 15 kg of this rennet casein, add 300 kg of water, and add 3.6% hydrochloric acid while suspending with a homomixer.
The pH was adjusted to 4.6. Then, after stirring was further continued for 30 minutes, the solidified casein was removed by filtration with a 30-mesh stainless steel filter, whereby the filtrate 85 containing casein-binding calcium and colloidal calcium was removed.
kg gained.

[0025]

Reference Example 2 In Reference Example 1, when obtaining a filtrate containing casein-binding calcium and colloidal calcium, the residue of acid casein obtained by filtration through a 30-mesh stainless steel filter was dissolved in water, A 20% acid casein solution (pH 7.0) was used. Next, to this acid casein solution, 0.5% of trypsin based on the weight of casein in the solution was added, and the mixture was reacted at pH 7.0 to 7.5 at 40 ° C for 4 hours. Immediately after the completion of the reaction, the pH was adjusted to 4.6, and the resulting precipitate was removed by centrifugation, and the supernatant was recovered. Then, 2.0% calcium chloride and 5 volumes of ethanol were added to the supernatant, stirred, mixed, and centrifuged to obtain 4 kg of a precipitate containing a phosphopeptide.

[0026]

Example 1 To 85 kg of the filtrate containing casein-binding calcium and colloidal calcium obtained in Reference Example 1, 2 kg of the precipitate containing the phosphopeptide obtained in Reference Example 2 was added, and the mixture was thoroughly stirred. Was adjusted to 6.7. The solution was concentrated under reduced pressure using a rotary evaporator to recover 20 kg of the concentrated solution, and the concentrated solution was filtered through a milk filter paper (Milpap) to remove insolubles. 1.4 kg of a calcium complex powder obtained by forming a complex of the basic calcium and colloidal calcium with the phosphopeptide was obtained. Table 1 shows the component composition (% by weight, hereinafter the same) of the obtained calcium composite powder. The contents in parentheses indicate the molar content.

[0027]

[Table 1] Calcium 11.6% (0.29 mol / 100g) Inorganic phosphorus 3.4% (0.11 mol / 100g) Organic phosphorus 2.2% (0.07 (Mol / 100g) Nitrogen 11.0% Sodium 4.0% ─────────────────────

[0028]

[Reference Example 3] 200 l of raw milk was centrifuged (5,000 xg, 10 minutes) to prepare skim milk, and the skim milk was treated with an ultrafiltration membrane (fraction molecular weight: 50,000 Da) to obtain lactose and milk. Casein from which soluble minerals were removed was prepared. A solution containing casein from which lactose and soluble minerals have been removed,
The pH was adjusted to 4.0 by adding 5.0% citric acid. Then, the solution was further centrifuged (5,000 × g, 10 minutes) with cooling to remove the coagulated casein, thereby obtaining a solution containing casein-binding calcium and colloidal calcium.

[0029]

Example 2 500 g of commercially available Meiji CPP III (manufactured by Meiji Seika) was added to the solution containing casein-binding calcium and colloidal calcium obtained in Reference Example 3, and the mixture was sufficiently stirred and adjusted to pH 7.0. . Then, this solution was concentrated under reduced pressure using a rotary evaporator, and further spray-dried to obtain 450 g of a calcium complex powder in which a complex of white casein-binding calcium and colloidal calcium and a phosphopeptide was formed. Table 2 shows the component composition of the obtained calcium composite powder. The figures in parentheses indicate the molar content.

[0030]

[Table 2] ───────────────────── Calcium 10.3% (0.26mol / 100g) Inorganic phosphorus 3.1% (0.10mol / 100g) Organic phosphorus 2.0% (0.06mol / 100g) (Mol / 100g) Nitrogen 10.8% Sodium 6.5% ─────────────────────

[0031]

Example 3 500 g of commercially available Meiji CPP III (manufactured by Meiji Seika) was added to the solution containing casein-binding calcium and colloidal calcium obtained in Reference Example 3, and the mixture was sufficiently stirred, and the pH was adjusted to 7.0. . Then, this solution is treated with an ultrafiltration membrane (fraction molecular weight: 10,000 Da) and desalted and concentrated.
Further, the resultant was spray-dried to obtain 430 g of white casein-binding calcium from which monovalent sodium ions had been removed and calcium complex powder in which a complex of colloidal calcium and phosphopeptide was formed. Table 3 shows the component composition of the obtained calcium composite powder. The figures in parentheses indicate the molar content.

[0032]

[Table 3] ───────────────────── Calcium 10.0% (0.25mol / 100g) Inorganic phosphorus 2.9% (0.10mol / 100g) Organic phosphorus 2.3% (0.08mol / 100g) (Mol / 100g) Nitrogen 12.4% Sodium 0.8% ─────────────────────

[0033]

Test Example 1 The solubility of each of the calcium composite powders obtained in Examples 1, 2 and 3 at neutral pH was examined. The same test was performed using casein-binding calcium and colloidal calcium obtained in Reference Example 1 as Control 1. Each sample was dissolved in deionized water so that the calcium concentration became 300 mg / 100 ml, and after sufficiently stirring, the mixture was centrifuged (2,000 rpm, 5 minutes) to measure the concentration of calcium contained in the supernatant. Then, the calcium solubilization rate was calculated by the following equation. Calcium solubilization rate (%) = concentration of calcium contained in supernatant (mg / 100 ml) / 300 (mg / 100 ml) × 100 The results are shown in Table 4.

[0034]

[Table 4] 濃度 Concentration of calcium contained in supernatant Calcium solubilization Rate ─────────────────────────────────── Example 1 300mg / 100ml 100% Example 2 300mg / 100ml 100% Example 3 300mg / 100ml 100% Control 1 2.4mg / 100ml 0.8% ──────────────────────────────── ───

According to this, the calcium in each of the calcium complexes obtained in Examples 1, 2 and 3 was completely solubilized, and the casein-binding calcium of Control 1 and the colloidal It can be seen that it has much better solubility than calcium in calcium.

[0036]

Test Example 2 Using the 10-week-old male SD rats as experimental animals, the in vivo absorption of each calcium complex obtained in Examples 1, 2 and 3 was examined. The same test was performed using casein-binding calcium and colloidal calcium obtained in Reference Example 1 as Control 1, and using milk as Control 2. The experimental group is 1
A group of 6 rats was orally administered to a rat fasted for 24 hours by a sonde with a suspension of each sample adjusted to have a calcium content of 10 mg / ml. At the time of sample administration, the contents of phosphorus and magnesium were adjusted to be the same, and the contents of protein and carbohydrate were also adjusted to be the same for purified casein, dialyzed whey protein, phosphopeptide and lactose. Four hours after the start of the administration of the sample, the stomach and intestine of the rat were excised, and each was ashed as it was. And
The amount of calcium digestion and absorption in the living body was calculated by the following equation.

(Amount of digestion and absorption of calcium in living body) = {(amount of calcium administered) − (amount of calcium remaining in stomach and intestine)} The results are shown in FIG. According to this, the calcium in each of the calcium complexes obtained in Example 1, Example 2 and Example 3 showed almost the same absorbency as the calcium in the milk of Control 2; It can be seen that the absorbency is remarkably improved as compared with the calcium in casein-binding calcium and colloidal calcium.

[0038]

Test Example 3 The use of each calcium complex obtained in Examples 1, 2 and 3 in vivo was examined using a 6-week-old male SD rat as an experimental animal. The same test was performed using casein-binding calcium and colloidal calcium obtained in Reference Example 1 as Control 1, and using milk as Control 2.

The experimental group consisted of 6 animals per group, and had a free intake of calcium-free feed and a calcium content of 20.
The suspension of each sample adjusted to mg / ml was
At 9 am every morning, 5 ml was orally administered by a sonde. At the time of sample administration, the contents of phosphorus and magnesium were adjusted to be the same, and the contents of proteins and carbohydrates were also adjusted.
Adjustments were made to be the same with purified casein, dialysed whey protein, phosphopeptides and lactose. Six weeks after the start of the administration of the sample, the bone density of the femur was measured using a bone density measuring device (DCS-600A manufactured by Aloka). Table 5 shows the results. In the table, the values in parentheses indicate the standard deviation. Also, ^a
Indicates that there is a significant difference (p <0.05) from control 1.

[0040]

[Table 5]

According to this, the group to which each of the calcium complexes obtained in Examples 1, 2 and 3 had a high bone density almost equivalent to the group to which the milk of Control 2 was administered. This indicates that the bone density is higher than that of the control 1 group to which casein-binding calcium and colloidal calcium were administered. Therefore, it can be said that the calcium complex of the present invention has excellent utility in vivo.

[0042]

Test Example 4 3.37 g of each calcium complex obtained in Examples 1, 2 and 3 was dissolved in 1 ml of pure water and HP
Analyzed by LC. Further, the calcium complex solution 1ml of organic phosphorus concentration of the calcium complex was adjusted to _{7mM, EDTA Na 2 · 2H 2} O 5mg and EDTA Na ₄
About · 4H ₂ O 8 mg added that dissociated calcium complex were also analyzed and subjected to HPLC in the same manner. H
The effluent was monitored at 235 nm using a TSK-GEL G 3000SW (7.5 mm × 60 cm) as a PLC column at a flow rate of 0.7 ml / min. The result is shown in FIG.

A to F in FIG. 2 show the following HPLC charts. A: HPLC chart of the calcium complex obtained in Example 1 B: HPLC chart of the calcium complex obtained in Example 1 dissociated by EDTA treatment C: Calcium complex obtained in Example 2 D: HPLC chart of the calcium complex obtained in Example 2 dissociated by EDTA treatment E: HPLC chart of the calcium complex obtained in Example 3 F: Obtained in Example 3 HPLC chart of calcium complex dissociated by EDTA treatment

According to this, the peaks of the respective calcium complexes obtained in Examples 1, 2 and 3 were obtained.
(I) is at a different position from the peak (II) of the monomeric phosphopeptide dissociated by EDTA treatment, and when the calcium complex is dissociated by EDTA treatment, the peak of the calcium complex ( I) disappears (Fig. B, D, F
), And a calcium complex in which casein-binding calcium and colloidal calcium and phosphopeptide formed a complex.

[0045]

Example 4 Using the calcium composite powder obtained in Example 3, tablets having calcium fortification in the formulation shown in Table 6 were produced. In addition, 5.0 g of calcium was contained in 100 g of the tablet.

[0046]

[Table 6] Calcium complex obtained in Example 3 50.0 (% by weight) Powder reduction Maltose starch syrup 47.0 Corn starch 1.0 Sucrose fatty acid ester 1.5 Flavor 0.5 ─────────────────────────────

[0047]

Example 5 The calcium composite powder obtained in Example 2 was added so that the amount added per 100 ml of raw milk was 1 g.
After homogenizing under a pressure of kg / cm ² , the mixture was sterilized at 120 ° C. for 4 seconds to produce calcium-enriched milk. In addition,
100 g of this milk contained 200 mg of calcium.

[0048]

Example 6 Using the calcium composite powder obtained in Example 1, a feed for breeding dogs (dog food) in which calcium was fortified by the composition shown in Table 7 was produced. In addition, 100 g of the dog breeding feed contained 2.1 g of calcium.

[0049]

[Table 7] ──────────────────────────── Soybean meal 10 (wt%) skim milk powder 14 soybean oil 4 corn oil 2 palm oil 2 Corn starch 30 Flour 15 Bran 8 Mixed vitamins 2 Mixed minerals 5 Cellulose 2 Calcium complex obtained in Example 1 6% ─────

[0050]

According to the present invention, the calcium complex in which casein-binding calcium and / or colloidal calcium and phosphoprotein and / or phosphopeptide form a complex is water-soluble at a neutral pH. In addition, the calcium complex has a feature of being excellent in solubility even when powdered. Furthermore, the calcium complex of the present invention also has a feature of being excellent in absorbability and utilization in vivo. Therefore, the calcium complex of the present invention can be added as a calcium agent to a medicine, food or drink, or feed to enhance calcium and prevent various bone diseases such as osteoporosis, fracture, rheumatism, arthritis, and back pain. And is useful for treatment.

[Brief description of the drawings]

FIG. 1 shows the results of an in vivo calcium absorption test in Test Example 2. The error bar indicates the 95% confidence interval, and the asterisk indicates a significant difference from control 1.
(p <0.05).

FIG. 2 shows the results of HPLC analysis of each calcium complex in Test Example 4 and those obtained by dissociating these calcium complexes by EDTA treatment.

Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 33/06 ABJ A61K 33/06 ABJ ADD ADD 38/17 AFC 37/16 AFC (72) Inventor Seiichiro Aoe 2-Shinsayama, Sayama, Saitama 8-9 Wako 2nd Shin-Sayama Mansion 406 (72) Inventor Ichiro Nakajima 4-7-29-304 Chiyoda, Sakado-shi, Saitama (72) Inventor Takayoshi Aoki 3-27-12, Hoshigamine, Kagoshima-shi, Kagoshima

Claims (6)

[Claims] 1. A calcium complex in which casein-binding calcium and / or colloidal calcium forms a complex with phosphoprotein and / or phosphopeptide. 2. A solution containing casein-binding calcium and / or colloidal calcium is added with and mixed with phosphoprotein and / or phosphopeptide, and the pH is adjusted to 5.5 or more to adjust the casein-binding calcium and / or colloidal calcium. 2. The method for producing a calcium complex according to claim 1, wherein a complex of calcium and phosphoprotein and / or phosphopeptide is formed. 3. The method according to claim 2, wherein after forming the complex, the mixture is treated with a membrane and desalted and concentrated. 4. The method according to claim 2, wherein the powder is formed by freeze-drying or spray-drying. 5. A calcium agent comprising the calcium complex according to claim 1 as an active ingredient. 6. A pharmaceutical, food or drink or feed in which calcium is fortified by blending the calcium complex according to claim 1.