JPH09291097A - Production of magnesium casein phosphopeptide preparation and food product, feed and medicine containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a magnesium casein phosphopeptide preparation which has high Mg content and is useful in food products, feeds and medicines by treating casein phosphopeptide as a hydrolyzate of casein with a cationic ion- exchange resin to remove metallic ions followed by reaction with a Mg salt in an aqueous medium. SOLUTION: Casein phosphopeptide prepared by hydrolysis of casein is brought into contact with a cationic ion-exchange resin to separate metallic ions from the casein phosphopeptide. Then, the metallic ion-free casein phosphopeptide is allowed to react with a magnesium salt, for example, magnesium oxide and/or magnesium carbonate and the like to introduce magnesium ions into the casein phosphopeptide whereby the objective magnesium-casein phosphopeptide preparation which has the weight ratio of 1-4N/P and 0.1-3Mg/P and is useful in food products, feeds or medicines.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a magnesium-casein phosphopeptide preparation having improved utilization of magnesium, and foods, feeds and pharmaceuticals containing the magnesium-casein phosphopeptide preparation.

The present invention also provides calcium-magnesium-improved utilization of calcium and magnesium.
The present invention relates to a method for producing a casein phosphopeptide preparation, and foods, feeds and medicines containing the calcium-magnesium-casein phosphopeptide preparation. Furthermore, the present invention relates to a mixed preparation of a calcium-casein phosphopeptide preparation with improved availability of calcium and the above magnesium-casein phosphopeptide preparation, as well as foods, feeds and medicaments containing said mixed preparation.

[0003]

2. Description of the Related Art Magnesium plays an important role in metabolism of a living body, and it is known that deficiency of magnesium induces neurological diseases, arrhythmias, heart diseases and the like. Further, relative insufficiency of magnesium with respect to calcium intake is regarded as important as a cause of various diseases. According to the 5th revised Japanese nutritional requirements, the target intake of magnesium for adults is 300 mg per day. However, it is reported that
It is 250 mg, which is not a sufficient level.

Magnesium salts designated as food additives include magnesium chloride and magnesium carbonate. However, for example, magnesium chloride is a compound having a strong deliquescent property and a strong bitter taste, and therefore it is difficult to use it as an oral magnesium supplement as it is. In addition, it has been reported that magnesium in diet shows various absorbability depending on the influence of its origin and coexisting dietary components. Even when viewed as magnesium salt alone,
Its absorbency varies. Therefore, nutritional improvement cannot always be achieved simply by increasing the intake of magnesium.

On the other hand, in the modern aging society, catastrophic osteoporosis is a syndrome that presents with clinical features such as bone mineral loss accompanying aging after the growth period and the resulting fractures in the bones and back pain. It is getting attention. Therefore, calcium can be supplied together with magnesium,
In addition, it is desired to develop a preparation having excellent absorbability or availability in vivo.

[0006]

The object of the present invention is to provide a magnesium preparation excellent in absorbability or availability of magnesium in vivo, a method for producing the same, and foods, feeds and pharmaceuticals containing the preparation. Especially. Another object of the present invention is to provide a preparation excellent in absorbability or availability of calcium and magnesium in a living body, a method for producing the preparation, and a food, a feed and a medicine containing the preparation.

[0007]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that metal ions such as calcium bound during the production of casein phosphopeptide (hereinafter referred to as CPP) are It was found that it is possible to obtain a magnesium-CPP preparation having excellent solubility and stability when it is reacted with magnesium after being removed from CPP. Furthermore, the magnesium-C
The present invention has been completed based on the finding that magnesium in a PP preparation has high absorbability or availability in vivo and effectively acts on bone mineral formation.

In the present invention, CPP obtained by decomposing casein and a cation exchange resin are brought into contact with each other to obtain the C
Magnesium-CPP, which includes a step of separating a metal ion from PP and a step of reacting the demetallized ion CPP obtained by the step and a magnesium salt in an aqueous medium to introduce the magnesium ion into the demetallized ion CPP.
A method of making a preparation is provided.

The present invention also provides a magnesium-CPP preparation obtained by the above production method. Furthermore,
The present invention provides a food product comprising the above magnesium-CPP preparation. Furthermore, the present invention provides the above magnesium-CP.
A feed containing a P preparation is provided. Furthermore, the present invention provides a medicament containing the above magnesium-CPP preparation as an active ingredient.

Further, the present invention comprises a step of separating a metal ion from the CPP by bringing the CPP obtained by decomposing casein into contact with a cation exchange resin, and a demetallized ion CPP obtained by the step. Calcium-magnesium-including a step of reacting a calcium salt and a magnesium salt in an aqueous medium to introduce calcium ions and magnesium ions into the demetallized ion CPP.
A method of making a CPP preparation is provided.

The present invention further provides a calcium-magnesium-CPP preparation obtained by the above-mentioned production method. Furthermore, the present invention provides a food product comprising the above calcium-magnesium-CPP preparation. Furthermore, the present invention provides a feed containing the above calcium-magnesium-CPP preparation. Furthermore, the present invention provides the above-mentioned calcium-
Provided is a medicine containing a magnesium-CPP preparation as an active ingredient.

Furthermore, the present invention comprises a step of contacting a CPP obtained by decomposing casein with a cation exchange resin to separate metal ions from the CPP, and a demetallized ion CPP and calcium obtained by the step. A calcium-CPP preparation obtained by a production method comprising reacting a salt in an aqueous medium to introduce a calcium ion into a demetallized ion CPP;
Provided is a mixed preparation mixed with a PP preparation.

The present invention further provides a food product containing the above-mentioned mixed preparation. Further, the present invention provides a feed containing the above mixed preparation. Furthermore, the present invention provides a medicament containing the above mixed preparation as an active ingredient. Hereinafter, the present invention will be described in detail.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION As casein as a raw material, either whole casein or fractionated casein can be used.
Here, whole casein means acid casein, sodium casein, calcium casein, and rennet casein prepared from whole milk or skim milk. In addition, the fractionated casein is
Α _{s1 -casein} separated from the above-mentioned total casein, α _s2 −
It refers to casein, κ-casein, λ-casein, β-casein and γ-casein, and these can be used alone or in combination of two or more. As a method for preparing fractionated casein, for example, a method of separating α-casein and β-casein from total casein by a urea fractionation method (J. Dairy
Sci., 35, 272 (1952)), a method for obtaining κ-casein from total casein by adding calcium salt (J. Food Sci., 43, 3).
97 (1978)), a method of hydrolyzing .kappa.-casein obtained from whole casein to obtain .beta.-casein (Japanese Patent Laid-Open No. 6-501455) and the like are known.

In the case of producing a magnesium-CPP preparation, the raw materials are all casein, α _s1 -casein, α
_It is preferable to use at least one fractionated casein selected from the group consisting of _s2 -casein and β-casein.
In the case of producing a calcium-magnesium-CPP preparation or a calcium-CPP preparation, as a raw material, whole casein, or a group consisting of α _s1 -casein, α _s2 -casein, β-casein and κ-casein. It is preferable to use at least one fractionated casein selected from

CP by decomposing raw material casein
The production of P can be performed by a conventionally known method.
For example, the following method may be mentioned, but the method is not limited to this. First, the casein solution is hydrolyzed with trypsin at pH 8.0 and 37 ° C. for 20 hours. Then the pH of the obtained reaction mixture is adjusted to 4.6 and the precipitate is removed by centrifugation. A calcium chloride solution is added to the obtained supernatant so that the calcium ion content is 20 mM, and then an equal amount of ethanol is added. CPP is obtained by collecting the formed precipitate by centrifugation and drying.

Further, magnesium-CPP preparation, calcium-magnesium-CPP preparation, calcium-C
In any production of PP preparations, the CPP obtained as described above is contacted with a cation exchange resin to separate and remove metal ions such as calcium, magnesium and iron from the CPP. Including steps. CP
The method of contacting P with the cation exchange resin is to remove the cation exchange resin after mixing the aqueous solution of CPP and the cation exchange resin in the container (in this case, the pH is usually 2.0 to 7.0). Another method is to pass an aqueous solution of CPP through a column packed with a cation exchange resin.

As the cation exchange resin, Amberlite IR-120B of divinylbenzene sulfonic acid type, DIAION SKIB (manufactured by Mitsubishi Chemical Co.) which is a styrene type strong acid cation exchange resin and the like can be used.

The magnesium-CPP preparation comprises CPP from which metal ions have been separated and removed by contact with the above-mentioned cation exchange resin (hereinafter referred to as demetallized CPP),
It can be obtained by reacting with a magnesium salt to introduce magnesium ions into the demetallized ion CPP. The reaction between the demetallized ion CPP and the magnesium salt is carried out, for example, by suspending the demetallized ion CPP in an aqueous medium such as ion-exchanged water and adding and mixing the magnesium salt. The order of adding the demetallizing ion CPP and the magnesium salt to the aqueous medium is not particularly limited. The concentration of demetallized CPP in the aqueous medium is preferably 1 to 30% by weight, more preferably 2 to 15% by weight. The amount of magnesium salt added is such that the amount of magnesium is preferably 0.5 to 7.0 g, more preferably 2.0 to 4.0 g per 100 g of demetallized ion CPP. This reaction is
It is preferable to carry out until the pH of the reaction mixture reaches 6.0 to 8.0. If the pH at the end of the reaction is too low, demetalization CPP
The reactivity is low due to its low solubility. Therefore, depending on the type and amount of magnesium salt to be added, if necessary,
It is preferable to adjust the pH of the reaction mixture to 6.0 or higher using sodium hydroxide, potassium hydroxide, hydrochloric acid or the like. Examples of the magnesium salt include magnesium salts that are usually used as food additives such as magnesium chloride, magnesium oxide, and magnesium carbonate, but it is said that the separation of the magnesium-CPP preparation after the reaction becomes easy. For reasons of preference, magnesium oxide and magnesium carbonate are preferred. After introducing magnesium ions in this way, for example, the insoluble matter in the reaction mixture is removed, and then freeze-dried to obtain a magnesium-CPP preparation.

Magnesium-obtained as described above
The magnesium content of CPP preparations is usually 10
As high as 100 to 700 mg per gram. Moreover, the preparation has high stability and excellent solubility. And, such a preparation has high availability of magnesium and effectively acts on bone mineral formation. In particular, the N / Mg ratio of such a preparation is 1 by weight.
When the Mg / P ratio is 0.1 to 3 on a weight basis, magnesium is highly utilized and effectively acts on bone mineral formation.

The calcium-magnesium-CPP preparation is produced by reacting the above demetallized ion CPP with a calcium salt and a magnesium salt to introduce calcium ion and magnesium ion into the demetallized ion CPP. The reaction of the demetallized ion CPP with the calcium salt and the magnesium salt is carried out, for example, by suspending the demetallized ion CPP in an aqueous medium such as ion-exchanged water and adding and mixing these salts. The order of adding the demetallizing ion CPP, the calcium salt and the magnesium salt to the aqueous medium is not particularly limited. The concentration of demetallized CPP in the aqueous medium is preferably 1 to 30% by weight, more preferably 2 to 15% by weight. The total amount of calcium salt and magnesium salt added is the demetalization CPP 100
The total amount of calcium and magnesium per g is preferably 0.1 to 20 g, more preferably 1.0 to 15 g. Further, by changing the ratio of the calcium salt and the magnesium salt, the amounts of calcium ion and magnesium ion introduced into CPP can be easily adjusted. This reaction is preferably carried out until the pH of the reaction mixture reaches 6.0 to 8.0. If the pH at the end of the reaction is too low, the solubility of the demetallized ion CPP is low and the reactivity decreases. Therefore, depending on the type and amount of the calcium salt and magnesium salt to be added, if necessary, sodium hydroxide, potassium hydroxide, hydrochloric acid or the like is used to adjust the pH of the reaction solution to 6.
It is preferably adjusted to 0 or more. Further, as the calcium salt, for example, calcium hydroxide, calcium carbonate,
Examples of the calcium salt that is usually used as a food additive such as calcium chloride, the reaction is preferably performed
Considering that the pH is 6.0 or more, it is preferable to use calcium hydroxide and calcium carbonate. Also,
Examples of the magnesium salt include the same salts as those exemplified in the production of the magnesium-CPP preparation. After introducing the calcium ion and the magnesium ion in this way, for example, the insoluble matter in the reaction mixture is removed and then freeze-dried to obtain a calcium-magnesium-CPP preparation.

The calcium content of the calcium-magnesium-CPP preparation obtained as described above is usually
300-1000 mg per 10 g of the preparation and the magnesium content is usually 100-700 mg per 10 g of the preparation. Moreover, the preparation has high stability and excellent solubility. And, such a preparation has high availability of calcium, magnesium and phosphorus, and effectively acts on bone mineral formation. In particular, the N / Ca ratio of such preparations is from 1 to 10 by weight.
The N / Mg ratio is 1 to 10 on a weight basis, the Ca / P ratio is 1 to 10 on a weight basis, and the Mg / P ratio is 0.1 on a weight basis.
When it is -10, the availability of calcium, magnesium and phosphorus is high, and it effectively acts on bone mineral formation.

The calcium-CPP preparation is demetalized by reacting CPP from which metal ions have been separated and removed by contact with the above cation exchange resin (hereinafter referred to as demetallized ion CPP) with a calcium salt. It is produced by introducing calcium ions into the ionic CPP. The reaction between the demetallization CPP and the calcium salt is carried out by suspending the demetalization CPP in an aqueous medium such as ion-exchanged water,
It is performed by adding and mixing a calcium salt. The order of adding the demetallizing ion CPP and the calcium salt to the aqueous medium is not particularly limited. Demetallized CPP in aqueous medium
The concentration is preferably 1 to 30% by weight, more preferably 2 to 15% by weight. The amount of calcium salt added is such that the amount of calcium is preferably 0.5 to 20.0 g, and more preferably 1.0 to 15.0 g per 100 g of demetallized CPP. Further, the pH of the reaction solution is preferably 4.0 or higher, more preferably 4.0 to 8.0. If the pH is too low, the solubility of the demetallized CPP is low and the reactivity decreases. Therefore, depending on the type and amount of calcium salt to be added, the pH of the reaction solution may be adjusted to 4.0 by using sodium hydroxide, potassium hydroxide, hydrochloric acid, etc.
It is preferable to adjust as described above. As the calcium salt, for example, calcium hydroxide, calcium carbonate, calcium salts which are usually used as a food additive such as calcium chloride can be mentioned.
Considering that it is performed at 4.0 or higher, it is preferable to use calcium hydroxide and calcium carbonate. After introducing the calcium ions in this manner, for example, the insoluble matter in the reaction mixture is removed and then freeze-dried to obtain a calcium-CPP preparation.

Calcium-C obtained as described above
The calcium content of PP preparations is usually as high as 500-1100 mg per 10 g of the preparation. Moreover, the preparation has high stability and excellent solubility. And, such a preparation has high availability of calcium and phosphorus, and effectively acts on bone mineral formation. In particular, the N / Ca ratio of such a preparation is 1 by weight.
When the Ca / P ratio is 1 to 3 on a weight basis,
The high availability of calcium and phosphorus effectively acts on bone mineral formation.

A magnesium-CPP preparation of the invention,
The mixed preparation obtained by mixing with the above-mentioned calcium-CPP preparation has high in vivo absorbability or availability of calcium, magnesium and phosphorus, and effectively acts on bone mineral formation.

By adding the magnesium-CPP preparation of the present invention to a food product, a magnesium supplement food product can be produced. Foods containing the magnesium-CPP preparation include milk, dairy products, soft drinks, confectionery,
Examples thereof include bread, noodles, paste products, processed foods, processed meat products, seasonings and the like. The magnesium-CPP preparation is usually added to foods by dissolution addition, powder mixing, kneading, coating and the like. Magnesium-C
The PP preparation can be added to a food product in an amount such that the amount of magnesium added to 100 g of the food product is usually 10 to 7000 mg, preferably 10 to 1000 mg.

Further, a magnesium supplemented feed can be produced by incorporating the magnesium-CPP preparation of the present invention into the feed. As the feed containing the magnesium-CPP preparation, a mixed feed of livestock, poultry, fish, pets or the like, or a raw material for the mixed feed (corn, wheat,
Barley, rice bran, soybean meal, fish meal, etc.). The magnesium-CPP preparation is usually added to the feed by dissolving, adding powder, kneading, coating and the like. Magnesium-CPP preparation is 100 g of feed
The magnesium can be added to the feed in an amount such that it is usually 10 to 7000 mg, preferably 10 to 1000 mg.

Furthermore, the magnesium-CPP preparation of the present invention is excellent in absorbability or availability of magnesium in the body, and therefore, for the prevention and / or treatment of heart diseases, or for the treatment of osteoporosis and other metabolic bone diseases. It is also useful as a medicine for patients to suppress bone mineral loss and promote bone mineral formation. In that case, the above magnesium-CPP preparation is formulated and administered orally. Examples of dosage forms include solutions, suspensions, capsules, powders, granules, fine granules, tablets and the like. When formulating, a solvent,
Additives such as dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants and lubricants can be used. The dosage of the preparation is usually in the range of 50 to 400 mg / kg (body weight) (Mg is 1 to 8 mg / kg) per day for an adult.
(Weight)) is appropriate.

Calcium-magnesium-CP of the present invention
Calcium and magnesium supplemented foods can be produced by incorporating the P preparation into foods. Examples of foods containing the calcium-magnesium CPP preparation include milk, dairy products, soft drinks, confectionery, bread, noodles, paste products, processed foods, processed meat products, seasonings and the like. Blending of the calcium-magnesium-CPP preparation into food is usually carried out by dissolution addition, powder blending, kneading, coating and the like. The calcium-magnesium-CPP preparation can be added to the food in an amount such that the total amount of calcium and magnesium per 100 g of the food is usually 10 to 10,000 mg, preferably 10 to 1000 mg.

By adding the calcium-magnesium-CPP preparation of the present invention to a feed, a calcium- and magnesium-supplemented feed can be produced.
Examples of the feed containing the calcium-magnesium-CPP preparation include mixed feeds for livestock, poultry, fish, pets, etc., or raw materials for mixed feeds (corn, wheat, barley, rice bran, soybean meal, fish meal, etc.). it can. The formulation of the calcium-magnesium-CPP preparation in the feed is
Usually, it is carried out by dissolution addition, powder blending, kneading, coating and the like. The calcium-magnesium-CPP preparation can be added to the feed in an amount such that the total amount of calcium and magnesium per 100 g of the feed is usually 10 to 10,000 mg, preferably 10 to 1000 mg.

Furthermore, since the calcium-magnesium-CPP preparation of the present invention is excellent in the absorbability or availability of calcium, magnesium and phosphorus in vivo, it is used for the prevention and / or treatment of heart diseases, or for osteoporosis, It is also useful as a drug for suppressing bone mineral loss and promoting bone mineral formation for patients with calcium malabsorption and other metabolic bone diseases. In that case, the above calcium-magnesium-CPP preparation is formulated and orally administered.
Examples of dosage forms are solutions, suspensions, capsules, powders,
Granules, fine particles, tablets and the like can be mentioned. Further, in the case of formulation, additives such as a solvent, a dispersant, an emulsifier, a buffer, a stabilizer, an excipient, a binder, a disintegrant and a lubricant can be used. The dose of the preparation is usually 50 to 400 mg / kg (body weight) (Ca is 3 to 30 mg / kg (body weight), Mg is 1 to 8 mg / kg (body weight)) per day for an adult. ) Is suitable.

A mixed preparation of a calcium-CPP preparation and a magnesium-CPP preparation is also excellent in absorbability or availability of calcium, magnesium and phosphorus in a living body. Supplementary foods can be produced.
Foods to which this mixed preparation is added include the same foods as those for the above calcium-magnesium-CPP preparation. The amount of this mixed preparation to be added to foods is also the same as in the case of the calcium-magnesium-CPP preparation.

Calcium-magnesium-CP of the present invention
The P preparation and the mixed preparation of the calcium-CPP preparation and the magnesium-CPP preparation are used as food, as feed, or for the prevention and / or treatment of heart diseases, or for osteoporosis, calcium malabsorption, and the like. It is also useful as a drug for suppressing bone mineral loss and promoting bone mineral formation for patients with metabolic bone disease. As the feed containing the prepared mixture, the above calcium-magnesium-C is used.
The same thing as the case of PP preparation is mentioned. Further, the amount of this mixed preparation compounded in the feed is the same as in the case of the calcium-magnesium-CPP preparation. Furthermore,
Even when this prepared mixture is used as a medicine, the above calcium-
As for the magnesium-CPP preparation.

[0034]

【Example】

Example 1 Preparation of Magnesium- CPP Preparation 9.0 Preparation of CPP Lactic acid casein (New Zealand Dairy Board) 9.0 kg
After being dispersed in 171.0 kg of water at 55 ° C, calcium hydroxide was gradually added to adjust the pH to 7.0. Next, trypsin (Novo
(Made by company) After adding 1.8 g, use calcium hydroxide
Hydrolysis was carried out at 50 ° C. for 4 hours while maintaining the pH at 7.8. Then, the obtained reaction mixture was cooled to 30 ° C.,
A 50% lactic acid solution was added to adjust the pH to 4.6. The generated precipitate was removed with a separator (α, manufactured by Laval). 50.0 kg of the obtained supernatant was mixed with 10 L of an anion exchanger (crosslinked chitosan beads, Fuji Spinning Co., Chitopearl) and the mixture was mixed at 10 ° C.
For 20 minutes. After collecting the anion exchanger by filtration and washing the anion exchanger, an aqueous solution of calcium hydroxide was added and the mixture was kept at pH 8.0 for 45 minutes to elute the adsorbed CPP. The eluate was concentrated under reduced pressure, desalted by electrodialysis, and then spray dried to obtain CP.
450 g of P powder was obtained.

Preparation of Demetallized Ion CPP 5.0 L of an aqueous solution prepared by dissolving the above CPP powder in water at a concentration of 5.0% (w / w) was added to an activated cation exchange resin (styrene strong acid cation exchange resin, diaion). , Mitsubishi Chemical Co., Ltd.) 1.2 kg was added and mixed. Then the pH of the solution is 2.0
Then, the cation exchange resin was removed by filtration, and the filtrate was freeze-dried. Thus, the demetallized ion CPP was obtained.

Preparation of Magnesium-CPP Preparation Ion-exchanged water from which carbon dioxide was sufficiently removed by boiling 2.8
13.8 g of magnesium oxide was suspended in L, and 100 g of the above demetallizing ion CPP was added. At this point the reaction mixture
The pH was 8.5. The reaction solution was kept at room temperature with stirring. The reaction was terminated when the magnesium oxide and the demetallized ion CPP were dissolved and the pH of the reaction mixture reached 6.8. The insoluble material in the reaction mixture was separated by centrifugation and removed, and the supernatant was freeze-dried. In this way, 98 g of magnesium-CPP preparation was obtained. The composition of this preparation is shown in Table 1.

[0037]

[Table 1]

Example 2 Preparation of Calcium-Magnesium-CPP Preparation 50 g of demetallized CPP prepared as in Example 1.
Was suspended in 1.4 L of ion-exchanged water and kept at room temperature with stirring to give 6.9 g of magnesium oxide and calcium hydroxide.
5.75 g was added and mixed. Magnesium oxide, calcium hydroxide and demetalized CPP are dissolved,
The reaction was completed when the pH reached 6.8. The insoluble material in the reaction mixture was separated by centrifugation and removed, and the supernatant was freeze-dried. In this way 49 g of the calcium-magnesium-CPP preparation was obtained. The composition of this preparation is shown in Table 2.

[0039]

[Table 2]

Example 3 Preparation of Calcium-CPP and Magnesium-CPP
Preparation of a mixed preparation with a demetallized ion CPP50.0 prepared in the same manner as in Example 1.
g was suspended in 1.4 L of ion-exchanged water, and 5.75 g of calcium hydroxide was mixed while being kept at room temperature with stirring (pH 6.
8). Then, the insoluble matter in the reaction mixture was separated by centrifugation and removed. In this way, calcium-CPP
A preparation (solution) was obtained. The magnesium-CPP preparation (solution) obtained in Example 1 before lyophilization was mixed with the above-mentioned calcium-CPP preparation (solution) at a weight ratio of 5: 1, and this was lyophilized to prepare a mixture. I got a thing. Its composition is shown in Table 3.

[0041]

[Table 3]

(Example 4) SD male rats (8 / group)
Was used to investigate the magnesium availability of the magnesium-CPP preparation prepared in Example 1. Low magnesium diet (magnesium level 17mg / 100g AIN93G (Jou
rnalof Nutrition, 123 (1993), 1939-1951), and fed for 5 weeks (magnesium-deficient diet group).

On the other hand, the magnesium-CP obtained in Example 1
A powdered feed for rats containing 2.4% by weight of the P preparation was prepared, and this was fed to the magnesium-deficient diet group rats and bred for 1 week (MgCPP diet group). The magnesium level of this MgCPP diet was 80 mg / 100 g, 78% by weight of which was supplied by the magnesium-CPP preparation. Components other than minerals were prepared according to AIN-93G. Also,
A control diet containing magnesium oxide as a magnesium source was also prepared, and this was fed to rats deficient in Mg and fed for 1 week (control diet group).

FIG. 1 is a graph showing the concentration of magnesium ions in plasma (mean value ± standard error) of each group. FIG.
There is a significant difference between a, b, and c (P <0.05).
FIG. 2 is a graph showing the amount of magnesium (average value ± standard error) per thigh bone dry weight in each group. FIG.
There is a significant difference between a, b, and c (P <0.05).

In the magnesium-CPP diet group, recovery of magnesium ion in plasma was observed, which was significantly higher than that in the control diet group (FIG. 1). The amount of magnesium in the femur of the magnesium-CPP diet group was significantly higher than that of the control diet group (Fig. 2). From these, it was shown that the bioavailability of the magnesium-CPP preparation was good.

(Example 5) Acute toxicity test: Six male and female SD rats aged 7 weeks were used to acutely administer a single 30% distilled water suspension of the magnesium-CPP preparation prepared in Example 1 once. A toxicity test was conducted. The suspension was forcibly administered at a dose of 20 g / kg (body weight) and observed for 14 days, but all showed normal growth and no deaths occurred. Moreover, no abnormal findings were observed.

Example 6 Acute Toxicity Test Using 6 7-week-old male and female SD rats, oral administration of a 30% distilled water suspension of the calcium-magnesium-CPP preparation prepared in Example 2 once Acute toxicity test was carried out. The suspension was forcibly administered at a dose of 20 g / kg (body weight) and observed for 14 days, but all showed normal growth and no deaths occurred. Moreover, no abnormal findings were observed.

Example 7 Acute Toxicity Test Using 6 7-week-old male and female SD rats, the calcium-CPP preparation and magnesium-CPP prepared in Example 3 were used.
Oral administration of 30% distilled water suspension of mixed preparation 1
A single acute toxicity test was conducted. 20 g of this suspension
/ Kg (body weight) was forcibly administered and observed for 14 days,
All showed normal growth and no deaths. Moreover, no abnormal findings were observed.

(Example 8) Formulation Example Production of tablets 800 parts by weight of the magnesium-CPP preparation prepared in Example 1 and 170 parts by weight of lactose were mixed, and then 100 ml of 50% ethanol was added and kneaded. . The obtained kneaded product was granulated using an extrusion granulator and dried at 70 ° C. for 2 hours with a hot air dryer. Next, 30 parts by weight of sucrose fatty acid ester (DK Ester F20W, manufactured by Daiichi Kogyo Seiyaku Co., Ltd.) was mixed with the obtained dry granules, and a tablet having a diameter of 5 mm and 100 mg per tablet was prepared with a tableting machine. The obtained 10 tablets had a magnesium content of 21 mg and a phosphorus content of 26 mg.

(Example 9) Formulation example Production of tablets Calcium-magnesium-CPP prepared in Example 2
After mixing 800 parts by weight of the preparation with 170 parts by weight of lactose,
100 ml of 50% ethanol was added and kneaded. The obtained kneaded product was granulated using an extrusion granulator and dried at 70 ° C. for 2 hours with a hot air dryer. Next, 30 parts by weight of sucrose fatty acid ester (DK Ester F20W, manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd.) was mixed with the obtained dry granules, and tablets having a diameter of 5 mm and 100 mg per tablet were prepared with a tableting machine. The 10 tablets thus obtained had a calcium content of 7 mg, a magnesium content of 19 mg, and a phosphorus content of 26 mg.

(Example 10) Formulation Example Production of tablets After mixing 800 parts by weight of the mixed preparation of the calcium-CPP preparation and the magnesium-CPP preparation prepared in Example 3 and 170 parts by weight of lactose, 100 ml of 50% ethanol was added and kneaded. The obtained kneaded product was granulated using an extrusion granulator and dried at 70 ° C. for 2 hours with a hot air dryer. Next, 30 parts by weight of sucrose fatty acid ester (DK Ester F20W, manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd.) was mixed with the obtained dry granules, and tablets having a diameter of 5 mm and 100 mg per tablet were prepared with a tableting machine. The calcium content in 10 tablets obtained was 9 mg,
The magnesium content was 17 mg and the phosphorus content was 26 mg.

(Example 11) Production of foods 10.6 kg of skim milk powder, 2.3 kg of unsalted butter, 200 g of the magnesium-CPP preparation prepared in Example 1 and 87.1 kg of water were mixed, dissolved and homogenized at 130 ° C. And heat sterilized for 2 seconds.
Then, it cooled below 5 degreeC. 1 kg of product in this way
A magnesium fortified milk drink containing 52 mg of magnesium per unit was obtained.

(Example 12) Production of foods 10.6 kg of skim milk powder, 2.3 kg of unsalted butter, 200 g of the calcium-magnesium-CPP preparation prepared in Example 2, water
87.1 kg were mixed, dissolved and homogenized, and then heat sterilized at 130 ° C. for 2 seconds. Then, it cooled below 5 degreeC. In this way, a calcium and magnesium fortified milk drink containing 18 mg of calcium and 48 mg of magnesium per kg of product was obtained.

(Example 13) Production of foods 10.6 kg of skim milk powder, 2.3 kg of unsalted butter, 200 g of a mixed preparation of the calcium-CPP preparation and the magnesium-CPP preparation prepared in Example 3, and 87.1 kg of water. After mixing, dissolving and homogenizing, the mixture was sterilized by heating at 130 ° C for 2 seconds. Then 5 ° C
Cooled below. In this way, a calcium and magnesium fortified milk drink containing 22 mg of calcium and 42 mg of magnesium per kg of product was obtained.

Example 14 Production of feed and sorghum 38.6% by weight, milo 27.9% by weight, barley
13% by weight, soybean meal (45%) 9.4% by weight, bran 1
% By weight, 2% by weight alfalfa meal, 5% molasses
%, Salt 0.5%, calcium carbonate 1.1%, tricalcium phosphate 1.3%, mineral mixture 0.1%.
The magnesium-CPP preparation prepared in Example 1 was mixed with a mixed feed for beef cattle fattening containing 0.1% by weight of a vitamin mixture and 0.1% by weight of a vitamin mixture to obtain a magnesium-enriched diet. .

(Example 15) Production of feed, 38.6% by weight of sorghum, 27.9% by weight of milo, and barley
13% by weight, soybean meal (45%) 9.4% by weight, bran 1
% By weight, 2% by weight alfalfa meal, 5% molasses
%, Salt 0.5%, calcium carbonate 1.1%, tricalcium phosphate 1.3%, mineral mixture 0.1%.
% Of calcium and 0.1% by weight of vitamin mixture, and 0.2 to 0.5% by weight of the calcium-magnesium-CPP preparation prepared in Example 2 in a mixed feed for beef fattening fortified with calcium and magnesium. I got the feed.

(Example 16) Production of feed and sorghum 38.6% by weight, mylo 27.9% by weight, barley
13% by weight, soybean meal (45%) 9.4% by weight, bran 1
% By weight, 2% by weight alfalfa meal, 5% molasses
%, Salt 0.5%, calcium carbonate 1.1%, tricalcium phosphate 1.3%, mineral mixture 0.1%.
% Of calcium and 0.1% by weight of vitamin mixture in a mixed feed for beef cattle fattening in a proportion of 0.2 to 0.5% by weight, prepared by mixing the calcium-CPP preparation and the magnesium-CPP preparation prepared in Example 3 with each other. The ingredients were blended to obtain a calcium and magnesium fortified feed.

[0058]

EFFECTS OF THE INVENTION According to the production method of the present invention, a magnesium-CPP preparation having a high magnesium content and a high magnesium utilization, which effectively acts on bone mineral formation, can be obtained. Therefore, this preparation is useful as a magnesium supplement food, feed, medicine and the like.

Further, according to the production method of the present invention, the calcium and magnesium contents are high, and
A calcium-magnesium-CPP preparation having a high utilization of magnesium and phosphorus and exhibiting a bone mineral formation promoting action, and a mixed preparation are obtained. These preparations are useful as calcium and magnesium supplements, feeds, medicines and the like.

[Brief description of drawings]

FIG. 1 is a graph showing the magnesium ion concentration (mean value ± standard error) in plasma of each group in Example 4.

FIG. 2 is a diagram showing the amount of magnesium (average value ± standard error) per dry weight of femur in each group in Example 4.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display area A61K 38/16 ABN A61K 37/14 ABN ABQ ABQ

Claims (25)

[Claims] 1. A step of separating a metal ion from the casein phosphopeptide by bringing a casein phosphopeptide obtained by decomposing casein into contact with a cation exchange resin, and a demetallated casein phosphopeptide obtained by the step. And a magnesium salt are reacted in an aqueous medium to introduce a magnesium ion into the demetallized ion casein phosphopeptide.
Process for the preparation of casein phosphopeptide preparations. 2. The casein is whole casein.
A method for producing the magnesium-casein phosphopeptide preparation according to 1. 3. The magnesium-casein phosphopeptide preparation according to claim 1, wherein the casein is at least one fractional casein selected from the group consisting of α _s1 -casein, α _s2 -casein and β-casein. Production method. 4. The method for producing a magnesium-casein phosphopeptide preparation according to claim 1, wherein the magnesium salt is magnesium oxide and / or magnesium carbonate. 5. The reaction of a demetallized casein phosphopeptide with a magnesium salt is carried out at a pH of the reaction mixture of 6.0 to 8.0.
The method for producing the magnesium-casein phosphopeptide preparation according to any one of claims 1 to 4, which is carried out until. 6. The magnesium-casein phosphopeptide preparation has an N / Mg ratio of 1 to 4 on a weight basis, and Mg / P
The method for producing a magnesium-casein phosphopeptide preparation according to any one of claims 1 to 5, wherein the ratio is 0.1 to 3 on a weight basis. 7. A magnesium-casein phosphopeptide preparation obtainable by the method according to any one of claims 1-6. 8. A food product comprising a magnesium-casein phosphopeptide preparation obtainable by the method according to any one of claims 1-6. 9. A feed comprising a magnesium-casein phosphopeptide preparation obtainable by the method according to any one of claims 1-6. 10. A medicament containing the magnesium-casein phosphopeptide preparation obtained by the method according to any one of claims 1 to 6 as an active ingredient. 11. A step of contacting a casein phosphopeptide obtained by decomposing casein with a cation exchange resin to separate a metal ion from the casein phosphopeptide, and a demetallized ion casein phospho obtained by the step. A method for producing a calcium-magnesium-casein phosphopeptide preparation, which comprises the step of reacting a peptide with a calcium salt and a magnesium salt in an aqueous medium to introduce calcium ions and magnesium ions into the demetallized ion casein phosphopeptide. 12. The method for producing a calcium-magnesium-casein phosphopeptide preparation according to claim 11, wherein the casein is whole casein. 13. The calcium-magnesium- according to claim 11, wherein the casein is at least one fractional casein selected from the group consisting of α _s1 -casein, α _s2 -casein, β-casein and κ-casein. Process for the preparation of casein phosphopeptide preparations. 14. The calcium-magnesium-casein according to any one of claims 11 to 13, wherein the magnesium salt is magnesium oxide and / or magnesium carbonate, and the calcium salt is calcium hydroxide and / or calcium carbonate. Method for producing a phosphopeptide preparation. 15. The reaction of demetallized casein phosphopeptide with calcium and magnesium salts is carried out until the pH of the reaction mixture reaches 6.0 to 8.0.
The manufacturing method according to any one of 1. 16. A calcium-magnesium-casein phosphopeptide preparation having an N / Ca ratio of 1 to 1 on a weight basis.
0, the N / Mg ratio is 1 to 10 on a weight basis, the Ca / P ratio is 1 to 10 on a weight basis, and the Mg / P ratio is 0.1 to 10 on a weight basis. The manufacturing method described in. 17. Calcium-magnesium-obtained by the method according to any one of claims 11 to 16.
Casein phosphopeptide preparation. 18. A food product comprising a calcium-magnesium-casein phosphopeptide preparation obtainable by the method according to any one of claims 11-16. 19. A feed comprising a calcium-magnesium-casein phosphopeptide preparation obtainable by the method according to any one of claims 11-16. 20. A medicine containing the preparation of calcium-magnesium-casein phosphopeptide obtained by the method according to any one of claims 11 to 16 as an active ingredient. 21. A step of contacting a casein phosphopeptide obtained by decomposing casein with a cation exchange resin to separate a metal ion from the casein phosphopeptide, and a demetallated casein phosphopeptide obtained by the step. 7. A calcium-casein phosphopeptide preparation obtained by a production method comprising the step of reacting a calcium salt with a calcium salt in an aqueous medium to introduce calcium ions into a demetallized ion casein phosphopeptide, and any one of claims 1 to 6. A mixed preparation prepared by mixing with the magnesium-casein phosphopeptide preparation obtained by the production method according to 1 above. 22. The mixed preparation has an N / Ca ratio of 1 to 10 by weight, an N / Mg ratio of 1 to 10 by weight, a Ca / P ratio of 1 to 10 by weight, and a Mg / P ratio. Is 0.1 to 10 on a weight basis,
18. A mixed preparation according to claim 17. 23. A food product comprising the mixed preparation according to claim 21 or 22. 24. A feed containing the mixed preparation according to claim 21 or 22. 25. A medicament containing the mixed preparation according to claim 21 or 22 as an active ingredient.