JPH08165249A - Composition having bone strengthening action - Google Patents

Abstract

PURPOSE: To provide a composition effective for bone strengthening of an osteoporosis patient of mainly aged people or a school child in a growth period. CONSTITUTION: This composition having bone strengthening action contains a basic protein fraction derived from milk and calcium derived from milk. This composition may be ingested in a shape of an oral administrating formulation or foods and drinks. Preferably, at least 50mg/100g of a basic protein fraction derived from milk and at least 250mg/100g of calcium derived from milk are contained in the case of foods, and at least 77mg/100g and 380mg/100g are contained respectively in the case of drinks. Absorbability of calcium is significantly increased with the composition having bone strengthening action and the bone strengthening action is reinforced. In the case of foods and drinks, the composition may be ingested in usual eating habit and effective for bone strengthening of an osteoporosis patient or a school child in a growing period.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a composition containing a milk-derived basic protein and milk-derived calcium and having a bone-reinforcing action. The composition having a bone-reinforcing action in the present invention is used in the form of an orally-administered preparation or a food or beverage (hereinafter, may be collectively referred to as a food or drink), and is used for bone-reinforcing in osteoporosis patients and growing school children, which are common in the elderly. Is effective for.

[0002]

2. Description of the Related Art In recent years, the number of patients with various bone diseases such as osteoporosis, bone fracture and low back pain has been increasing in the elderly. It is said that this is due to insufficient intake of calcium, decreased calcium absorption ability, imbalance of postmenopausal hormones, and the like. Thus, in order to prevent various bone diseases such as osteoporosis and bone fracture, which are common in the elderly, it is effective to increase the bone mass as much as possible to increase the peak bone mass. And increasing the maximum bone mass is nothing but strengthening the bone. As described above, in the current trend of increasing the number of patients with various bone diseases, for the purpose of bone strengthening, calcium carbonate, calcium phosphate, calcium salts such as calcium lactate and whey calcium, beef bone powder,
Natural calcium agents such as egg shells have been added to foods either alone or with materials thought to promote calcium absorption such as caseinphosphopeptides.

However, when these calcium is ingested as food together with other ingredients, its absorption rate is 50%.
It is said that more than half is not absorbed and is discharged outside the body. In addition, since calcium absorbed in the body has different affinity to bone depending on its form and the types of other nutrients taken at the same time, it may not show the effects of improving bone metabolism and bone strengthening. In addition, vitamin D ₃ and calcitonin preparations are known as drugs for treating osteoporosis and bone strengthening. However, when these drugs are used, side effects such as tinnitus, headache, and loss of appetite may be associated. Further, at present, the substances used as these medicines cannot be added to foods and drinks in terms of safety and economy. Therefore, due to the nature of the disease called osteoporosis, it is desired to develop an orally-administered preparation or a food or drink that can be taken orally for a long period of time and directly acts on bone, and its preventive or therapeutic effect can be expected. .

It is necessary to ingest a sufficient amount of calcium for bone strengthening. In general, foods rich in calcium include milk and dairy products, small fish, shellfish, etc. Among them, it has become known in recent years that milk-derived calcium can be effectively utilized by the living body [VK K
ansal and S. Chandhary, Milchwissenschaft, 37, 261
(1982)]. In order to ingest calcium, it is sufficient to ingest a large amount of milk and dairy products, but in view of nutritional balance and calorie intake, there is a problem that dairy products cannot be indiscriminately ingested.

[0005]

DISCLOSURE OF THE INVENTION The inventors of the present invention have been searching for fractions having a bone-reinforcing action contained in food materials, and that the basic protein fraction contained in milk has a bone-reinforcing action. Revealed. It was found that this basic protein can be easily obtained by contacting milk or a raw material derived from milk with a cation exchanger, and that bone can be strengthened by orally ingesting the obtained basic protein, First applied as a bone strengthening agent (Japanese Patent Application No. 6-261609)
No.) And when further studying the effective utilization method of this basic protein fraction in the actual diet,
It was found that when this is ingested at the same time as milk-derived calcium, the absorption rate of milk calcium is improved and the bone strengthening effect is significantly enhanced, and the present invention has been completed.

[0006]

DISCLOSURE OF THE INVENTION The present invention is a composition containing a milk-derived basic protein and milk-derived calcium and having a bone-reinforcing action. The composition having a bone-reinforcing effect of the present invention is used in the form of an orally-administered preparation or a food or drink. The composition of the present invention contains 50 mg / 100 g or more of milk-derived basic protein fraction and 250 mg / 100 g or more of milk-derived calcium in terms of solids. Even in the form of food, 50% of the basic protein fraction derived from milk is calculated on a solid basis.
mg / 100g or more and milk-derived calcium 250 mg / 100
Contains more than g. Further, the composition of the present invention, in the form of a beverage, the milk-derived basic protein fraction is 77 mg / 100 g or more in terms of solid, and the milk-derived calcium is 380 mg /
Consists of more than 100g. Further, the amino acid composition of the milk-derived basic protein fraction constituting the composition of the present invention contains 15% by weight or more of a basic amino acid. Further, the milk-derived basic protein fraction constituting the composition of the present invention,
It contains insulin-like growth factor-1. The milk-derived basic protein fraction constituting the composition of the present invention contains insulin-like growth factor-1 in an amount of 200 μg / 100 g or more in terms of solid. The milk-derived basic protein fraction constituting the composition of the present invention is a fraction obtained by contacting milk or a milk-derived raw material with a cation exchange resin and then eluting with a solution having a salt concentration of 0.1 to 1.0 M. is there.

Hereinafter, the present invention will be described in detail. The basic protein derived from milk used in the present invention is milk,
It is obtained from mammalian milk such as human milk, goat milk, and sheep milk. It acts directly on bones, and by ingesting it simultaneously with milk-derived calcium, its bone strengthening effect can be greatly enhanced. It is possible. The composition having a bone-reinforcing effect of the present invention can be used in the form of an orally-administered preparation or in the form of a food or drink as long as it contains a milk-derived basic protein and milk-derived calcium at the same time. Examples of the form of the oral administration preparation include tablets, capsules, granules, powders, pills, drinks, syrups and the like. The food and drink may be in any form, and examples thereof include process cheese, fermented milk, and processed foods. Examples of drinks include drinkable milk, drink yogurt, coffee drinks, fruit juices, etc., and there is no limitation as long as they are foods and drinks obtained by a production method in which the activity of the final product is not lost. In foods and drinks in which milk is the main raw material, milk-derived calcium is inherently contained therein, and in this case, without adding new milk-derived calcium, this milk-derived calcium is used as an active ingredient. It is also possible and may be further strengthened.

As a method for preparing a milk-derived basic protein, a method using alginic acid gel (JP-A-61-246)
198), a method using a sulfated ester compound (JP-A-63-255300), a method using inorganic porous particles (JP-A-1-86839), and a method using a cation exchanger (Patent Document 1). (Kaihei 5-202098), a method for producing a bovine insulin-like growth factor-1 containing substance (Japanese Patent Application No. 6-85333)
, Etc., the milk-derived basic protein used in the present invention is obtained by the method for producing a bovine insulin-like growth factor-1 containing substance described in Japanese Patent Application No. 6-85333. Alternatively, it is preferable to use a fraction obtained by contacting milk or a raw material derived from milk with a cation exchange resin and then eluting a fraction adsorbed on the resin with a salt solution.

When the above-mentioned milk or milk-derived raw material is brought into contact with a cation exchange resin and then the fraction adsorbed on the resin is eluted with a salt solution, skim milk or whey having a pH of 4 to 8 is obtained. After contacting a milk material such as cation exchange resin (preferably one having a sulfonic acid group as an exchange group), the resin has a salt concentration of 0.1 M or more and 1.0 M or less, such as sodium chloride, sodium carbonate or citric acid. Elute with an aqueous solution such as sodium and collect the eluted fraction. When the pH of the dairy raw material is 4 or less, the basic protein content in the fraction obtained by adsorbing proteins other than the basic protein to the cation exchanger decreases, while when the pH is 8 or more, the basic protein content is basic. Protein recovery is reduced. The salt concentration required for elution of the basic protein from the cation exchanger is 1.0 M or less, but if the salt concentration of the eluate is less than 0.1 M, elution will be insufficient, which is not preferable. The obtained fraction is then subjected to an ion exchange method,
It can be desalted and concentrated by a means such as a reverse osmosis method, an ultrafiltration method, an electrodialysis method, etc., and if necessary, dried and powdered. The basic protein fraction thus obtained contains about 40% or more by weight of solids of lactoferrin and lactoperoxidase. Insulin-like growth factor-1 (hereinafter referred to as IGF-1), which has an action of activating osteoblasts and strengthening bone, [Shiro Saito et al., Japan Clinic, 48, 2779 (1990)] is 200 to 500 per 100 g of solid.
Contains μg. And in the amino acid composition of this fraction
It contains 15% by weight or more of basic amino acids.

The milk-derived calcium in the composition of the present invention is
For example, a method for producing a milk-derived calcium agent by adding acid to milk casein to adjust the pH to 5.5 or less, selectively separating casein-binding calcium and colloidal calcium from the casein, and recovering the same (JP-A-6- 125740), calcium obtained according to Japanese Patent No.
Milk-derived calcium such as (manufactured by DMV) or Chugai CA-18 (manufactured by Chugai Pharmaceutical) can be used.

When an oral administration preparation is produced using the milk-derived basic protein and milk-derived calcium thus obtained, the milk-derived basic protein and the milk-derived calcium as active ingredients are used. Are ingredients commonly used in the field of formulation, for example, excipients such as fillers, diluents, solvents and fillers; solubilizers, solubilizers, emulsifiers, suspending agents, dispersants, binding agents. Auxiliary agents such as agents, lubricants, coating agents and sustained-release agents; or additives such as antioxidants, preservatives, brighteners, sweeteners, coloring agents, flavoring agents, etc. According to the above, it can be molded into an appropriate form or can be made into a liquid agent. The orally-administered preparation may contain, in addition to the milk-derived basic protein and the milk-derived calcium, one or more other medicinal components.

Further, when blended into food, as is clear from the results of animal experiments described later, when 100 mg of solid protein and 50 mg or more of basic protein and 250 mg or more of calcium derived from milk are simultaneously blended and ingested Bone strengthening effect is recognized in the. In beverages, the same effect is observed when 77 mg or more of basic protein and 380 mg or more of calcium derived from milk are mixed per 100 g of solid. In the food and drink containing the milk-derived basic protein and the milk-derived calcium as described above, IGF-1 is 0.5
Included over μg. When blending milk-derived basic proteins based on ordinary dairy products, for example, milk or fermented milk contains 900 mg or more milk-derived calcium per 100 g of solid content, and processed cheese contains approximately 620m
Since it contains about g of calcium derived from milk, bone-strengthening action can be expected even if only a predetermined amount of milk-derived basic protein is added to them. On the other hand, in foods containing no milk components or foods containing a certain amount of milk components or less, milk-derived basic proteins must be added together with milk-derived calcium. The addition method of these is not particularly limited, and a usual method is used. Also often
Bioactive proteins are often inactivated by heating and lose their potency, but regarding the basic protein fraction,
Heating to the normal sterilization temperature does not lose its efficacy. When milk-derived basic protein is added to drinking milk, first, milk-derived basic protein is added to a concentration of 10 mg or more per 100 ml of raw milk, homogenized, sterilized, and cooled, and then filled in a container.

In fermented milk, a raw material milk, for example skim milk or skim milk powder, dissolved in water and dissolved is heated and sterilized, and then cooled, and a predetermined amount of milk-derived basic protein is added thereto to obtain Streptococcus. Lactis subspecies thermophilus (S. lactis .sp. Thermophilus ),
Lactobacillus helveticus ,
Lactobacillus cremoris ( L. cremoris ), Lactobacillus acidophilus ( L. acidophilus ) or Bifidobacterial species ( Bifidobacteriu)
Inoculate with one or more lactic acid bacteria such as m species) to ferment. When the lactic acid acidity is 0.8 to 1.5% or the pH is 4.0 to 4.5, the temperature is cooled to 10 ° C or lower.

As a method for adding a milk-derived basic protein to the fermented milk, as described above, the basic protein is added to the starter culture and then inoculated into a milk medium to ferment, or the milk after heat sterilization. There is a method in which lactic acid bacteria are inoculated into the medium to ferment it, and then a predetermined amount of milk-derived basic protein is added. However, the method of fermenting after adding the basic protein to the starter culture is preferable because the basic protein is uniformly dispersed in the obtained fermented milk. This is, for example, in stirring type yogurt, even if it is not possible to uniformly disperse in the fermented milk even if basic protein is added after fermentation, or in the standing type yogurt, the medium containing the starter culture in the individual food container. Since it is filled and fermented, there is a problem that the basic protein derived from milk cannot be added substantially.

When the milk-derived basic protein is used in fermented milk, the amount of the milk-derived basic protein added to the starter culture is calculated by calculating backward from the concentration of the milk-derived basic protein in the final product. Ask. For example, if the concentration of milk-derived basic protein in the final product is 50 mg per 100 g of solid and 5% of starter culture is added, the amount of milk-derived basic protein added to the starter is 100 g of solid. It becomes 100 mg. In the case of producing yogurt, according to a conventional method, raw milk having a milk fat content standardized to about 3.5% is used as a culture medium, which is sterilized, and then the starter culture prepared as described above is inoculated and fermented. When sour cream is produced, a cream containing about 45% milk fat is used as a medium, and when producing quark, skim milk is used as a medium. The sterilization conditions of the medium are not particularly limited, and commonly used conditions such as 90 ° C. for 10 minutes or 97 ° C. for 15 seconds can be adopted. To inoculate the starter culture, cool the medium to the culture temperature (about 25 to 45 ℃, depending on the product), and then add about 1 to 10% of the milk yield. Filling after inoculation,
Steps such as fermentation, flavoring, cooling and the like can be carried out according to conventional methods.

In order to mix the basic protein derived from milk into the processed cheese, it may be added together with an auxiliary material such as a molten salt when emulsifying the raw material cheese, or may be added in advance to the added water or the molten salt. It is possible to employ a method in which the raw material cheese is mixed well and then emulsified. The emulsification temperature may be the same emulsification temperature as in the method for producing an ordinary processed cheese, and the water content and pH are not particularly limited.

Next, the present invention will be described in detail by showing Examples and Test Examples. The examples described below are examples showing the present invention more specifically, and the present invention is not limited thereto.

[0018]

[Example 1] Preparation of basic protein Column packed with 400 g of cation exchange resin sulfonated chitopearl (manufactured by Fuji Spinning Co., Ltd.) (diameter 5 cm x height 30 c
m) was thoroughly washed with deionized water, and then 40 liters of unsterilized skim milk (pH 6.7) was passed through this column at a flow rate of 25 ml / min. After passing, wash the column thoroughly with deionized water and
The basic protein fraction adsorbed on the resin was eluted with 0.02M carbonate buffer (pH 7.0) containing 98M sodium chloride. Then, after desalting this eluate with a reverse osmosis membrane and concentrating it,
Lyophilization gave 21 g of powdery basic protein fraction.

Component Composition of Basic Protein Fraction The component composition of the basic protein fraction obtained above was analyzed by a conventional method. Table 1 shows the results.

[0020]

[Table 1]

Protein Composition in Basic Protein Fraction The basic protein fraction obtained above was analyzed for protein composition according to a conventional method. The lactoferrin and lactoperoxidase contents were measured by a usual enzyme immunoassay method, and the IGF-1 content was measured by a radioimmunoassay method. The results are shown in Table 2.

[0022]

[Table 2]

Amino Acid Composition in Basic Protein Fraction The amino acid composition of the basic protein fraction obtained above was analyzed by a conventional method. Table 3 shows the results.

[0024]

[Table 3]

[0025]

Example 2 The milk-derived basic protein obtained in Example 1 was used to produce drinking milk. Per 100cc of raw milk,
2, 10, 20, 40, and 100 mg of basic protein derived from milk were added, homogenized at 120 kg / cm ² , and sterilized at 120 ° C for 4 seconds. Then, cooling and filling were performed according to a conventional method. Even if the obtained drinking milk contained basic protein derived from milk, the flavor was completely the same as that of ordinary drinking milk. Calcium content in drinking milk is 130m
It was g / 100 ml (about 1030 mg / 100 g in terms of solid), and the IGF-1 content was measured by radioimmunoassay, and as shown in Table 4.

[0026]

[Table 4]

[0027]

Example 3 Yogurt was produced using the basic protein obtained in Example 1. Skim milk powder has a solid content of 12%
Dissolve in water so that the amount of basic protein derived from milk is 2, 10, 20, 40, and 100 mg per 100 g of yogurt, and sterilize by heating at 90 ° C for 20 minutes. , Cooled to 25 ℃, L. acidophilus and S. th
ermophilus was inoculated. Lactic acid degree is 1.0%, pH is 4.3
When it became, it was cooled to 5 ° C. 5% of the starter culture thus obtained was inoculated into sterilized raw milk having a fat content of 3.5%. After inoculating the starter, fermentation, flavoring and cooling were carried out in the usual manner. Also, the obtained yogurt, even if it contains a basic protein fraction,
It had no effect on flavor, physical properties and texture. The calcium content in yogurt was 130 mg / 100 g (about 1030 mg / 100 g in terms of solid), and the IGF-1 content was measured by radioimmunoassay, and as shown in Table 5.

[0028]

[Table 5]

[0029]

Example 4 Using the basic protein fraction obtained in Example 1, processed cheese was produced. As raw material cheese, gouda cheese and cheddar cheese were mixed at a ratio of 1: 1 and 2% of sodium citrate as a molten salt was added to the raw material cheese, 10% of water and 100 g of processed cheese.
The basic protein fraction derived from milk was blended so that the amount per unit was 10, 20, 50, 100, and 150 mg, and the mixture was emulsified according to a conventional method at an emulsification temperature of 85 ° C. After emulsification, the cheese was filled in a carton and cooled at 5 ° C for 2 days and nights. The calcium content of the obtained processed cheese was 620 mg / 100 g, and the IGF-1 content was as shown in Table 6 as a result of measurement by the radioimmunoassay method. Moreover, even if the obtained processed cheese contained the basic protein fraction, it did not affect flavor, physical properties, and texture at all.

[0030]

[Table 6] ─────────────────────────
──────────

[0031]

Example 5 As the milk-derived basic protein powder and milk-derived calcium obtained in Example 1, lactobal
(DMV) powder was filled in a soft capsule made of gelatin so that 50 mg of milk-derived basic protein and 250 mg of milk-derived calcium were added per capsule to give an orally-administered preparation having bone-reinforcing action. It was

Next, test examples in which the effects of the present invention have been confirmed by animal experiments will be shown.

[Test Example 1] As the milk-derived basic protein and milk-derived calcium obtained in Example 1, lactobal (DMV
The amount of basic protein derived from milk necessary for expressing the bone-reinforcing effect was examined by an animal experiment. Four-week-old SD female rats were used as experimental animals. After preliminarily breeding for 1 week, an oophorectomy operation was performed, and then the animals were fed with a calcium deficient diet for 5 weeks and used for animal experiments. still,
The rats that had their ovaries removed and were kept on a calcium-deficient diet for 5 weeks were clearly in an osteoporotic state. The rats in which this osteoporotic state was induced were bred by the diet shown in Table 7 (6 rats per group) (the same applies to the following experimental examples).

[0033]

[Table 7]

After 4 weeks, both femurs of the rats in each test group were excised and the bone strength was measured by a bone breaking force measuring device. The result is shown in FIG. According to this, when the same amount of calcium derived from milk was added, in the group (D group, E group) in which 50 mg or more of basic protein derived from milk was added to 100 g of feed, the thigh was compared to the control group (Group A). Bone fracture stress is statistical (Tukey
-Kramer method) showed a significantly high value.

[0035]

Test Example 2 Using the milk-derived basic protein obtained in Example 1 and milk-derived calcium as lactobal (manufactured by DMV), animals were fed in the same manner as in Test Example 1 using the feeds shown in Table 8. An experiment was conducted to examine the amount of milk-derived calcium required to exert the bone strengthening effect. In addition, calcium carbonate was added as a calcium source to the control groups (Groups A to D).

[0036]

[Table 8]

The bone strength was measured by the same method as in Experimental Example 1. The result is shown in FIG. When a certain amount of milk-derived basic protein was added to the feed, the femurs in the group (G group, H group) containing 250 mg / 100 g or more of milk-derived calcium were compared to the control group (C group, D group). Breaking stress is statistical
(Tukey-Kramer method) showed a significantly high value.

[0038]

[Test Example 3] Regarding the drinking milk containing the basic protein obtained in Example 2, the amount of the basic protein derived from milk and the bone thereof were added in the same manner as in Test Example 1 using the feed shown in Table 9. The relationship of strengthening action was examined. 250 ml of drinking milk containing the basic protein derived from milk obtained in Example 2
Was freeze-dried in advance, and 31 g of this powder was blended. This drinking milk powder contained 10.3 mg / g of calcium. In the control group (group A), calcium carbonate was used as the calcium source, and casein, whey protein, milk fat, and lactose were added according to the composition of the milk powder for drinking. The amount of milk-derived basic protein indicates the amount of milk-derived basic protein in the mixed feed, and the amount of milk-derived basic protein in 100 ml of drinking milk mixed with this in the feed. When converted to
, B group 2 mg, C group 10 mg, D group 20 mg, E group 40 mg,
F group will be 100 mg. The values in parentheses in the table are derived from drinking milk powder.

[0039]

[Table 9]

The bone strength measurement test was carried out in the same manner as in Test Example 1. The result is shown in FIG. According to this, compared with the control group (Group A), the femoral fracture stress was statistically compared in the group (C to F group) in which powdered basic protein derived from milk was contained in an amount of 10 mg or more per 100 ml of drinking milk. Target (Tukey-K
The remar method) showed a significantly high value. Further, the femoral fracture stress showed a higher value as the amount of the basic protein fraction added increased.

[0041]

TEST EXAMPLE 4 In the same manner as in Test Example 1, the feeds shown in Table 10 were used to examine the relationship between the amount of milk-derived calcium added and its bone-reinforcing action. In the feed, casein, whey protein, milk fat, and lactose were mixed according to the powder obtained by freeze-drying 500 cc of drinking milk. Control group (A
Group), calcium carbonate as a calcium source, B to F
In the group, milk-derived calcium (lactobar) was added in addition to calcium carbonate. The basic protein derived from milk is 100 mg / 100 g, which is 20 mg when converted to the amount of basic protein derived from milk in 100 cc of drinking milk from the composition of the milk powder for drinking mixed with the feed.

[0042]

[Table 10]

The bone strength was measured in the same manner as in Test Example 1. FIG. 4 shows the results. According to this, the femoral rupture stress was higher than that of the control group (group A) to which the same amount of milk-derived basic protein was added, when milk-derived calcium was added to 100 m of drinking milk.
Statistical (Tukey-Kremar method) values were significantly higher in the groups (E and F groups) containing more than 50 mg / l (250 mg / 100 g of feed). Further, the femoral fracture stress showed a higher value as the amount of milk-derived calcium added increased.

[0044]

[Test Example 5] With respect to the yogurt containing the milk-derived basic protein obtained in Example 3, the feed amount shown in Table 11 was used in the same manner as in Test Example 1, and the added amount of the milk-derived basic protein was added. And the relation between the bone strengthening effect was investigated.
Incidentally, 250 g of yogurt containing the basic protein derived from milk obtained in Example 3 was preliminarily freeze-dried to each feed except for the group A and mixed as powder 31 g. This yogurt powder contained 10.3 mg / g of calcium. In the control group (Group A), calcium carbonate was used as the calcium source, and casein, whey protein, milk fat, and lactose were added according to the composition of the yogurt powder. The amount of milk-derived basic protein indicates the amount of milk-derived basic protein in the mixed feed, and the amount of milk-derived basic protein in 100 g of yogurt mixed with this in the feed. When converted to
, B group 2 mg, C group 10 mg, D group 20 mg, E group 40 m
The g and F groups will be 100 mg. Numerical values in parentheses in the table are derived from yogurt powder.

[0045]

[Table 11]

The bone strength was measured by the same method as in Test Example 1. The result is shown in FIG. According to this, compared with the control group (Group A), the femoral fracture stress was statistically higher in the group (C to F group) in which yogurt containing 10 mg or more of milk-derived basic protein per 100 g was pulverized and mixed (Group C to F). (Tukey-Kremar method)
Showed a significantly high value. The femoral fracture stress is
The value increased as the amount of basic protein fraction added increased.

[0047]

Test Example 6 With respect to the processed cheese containing the milk-derived basic protein obtained in Example 4, the feed shown in Table 12 was used in the same manner as in Test Example 1, and the milk-derived basic protein was added. The relationship between the amount and its bone strengthening effect was investigated. The amount of milk-derived basic protein indicates the amount of milk-derived basic protein in the mixed feed,
Converting this to the amount of milk-derived basic protein in 100 g of cheese mixed in the feed, A group was 0 mg and B group was 10 m.
g, C group 20 mg, D group 50 mg, E group 100 mg, F group 150
It becomes mg.

[0048]

[Table 12]

The bone strength was measured in the same manner as in Test Example 1. The result is shown in FIG. According to this, compared with the control group (group A), the femoral fracture stress was statistically higher in the group (D, E, F groups) in which the cheese containing 50 mg or more of the basic protein derived from milk was added to the feed (group D, E, F). Showed a significantly high value.
Further, the femoral fracture stress showed a higher value as the amount of the basic protein fraction added increased.

[0050]

[Comparative Example 1] The processed cheese containing the basic protein concentrate obtained in Example 4 was fed with the feeds shown in Table 13 in the same manner as in Test Example 1 and the bone strengthening effect of calcium was determined by animal experiments. It was compared with the case where calcium carbonate or beef bone powder was used as. The values in parentheses in the table are derived from cheese.

[0051]

[Table 13]

The bone strength was measured by the same method as in Test Example 1. FIG. 7 shows the result. According to this, even if it contains the same amount of milk-derived basic protein fraction and the same amount of calcium, calcium in cheese than calcium carbonate (group A) and beef bone meal (group B) added as calcium sources. The rupture stress of the femur of those to which was added as a calcium source (Group C) showed a statistically significantly high value.

[0053]

[Comparative Example 2] A feed containing a yogurt powder not containing a milk-derived basic protein fraction (Group A), and a feed containing a milk-derived basic protein fraction-free yogurt powder enriched with milk-derived calcium ( (Group B), a feed containing a yogurt powder containing a milk-derived basic protein fraction (Group C) were prepared respectively, and animal experiments were carried out with these to enhance the milk-derived calcium alone and the milk. A comparative experiment was carried out using the feeds shown in Table 14 for the bone strengthening effect when the calcium-derived and basic protein fractions derived from milk were fortified. The values in parentheses in the table are derived from yogurt powder.

[0054]

[Table 14]

The bone strength was measured by the same method as in Test Example 1. FIG. 8 shows the result. Group A (control group)
No statistically significant difference was observed between groups B and B (calcium-enhanced group), but a comparison between groups A and C (milk-derived basic protein added group) showed that the rats in group C were The results show that the femoral fracture stress is statistically significant.
From this, the bone strengthening effect is most effective when the milk-derived calcium and the milk-derived basic protein fraction are mixed at the same time, and it is not possible to expect a sufficient bone strengthening effect by strengthening the milk-derived calcium alone. Was confirmed.

[0056]

The composition of the present invention containing a milk-derived basic protein and milk-derived calcium significantly improves the absorption rate of calcium and enhances the bone strengthening effect. Further, the composition having a bone-reinforcing effect of the present invention can be ingested in the form of an orally-administered preparation or food and drink, and has no side effects at all because it is made of milk as a raw material, particularly in the case of food and drink, Since it can be taken in daily dietary habits, it is effective in the prevention or treatment of various bone and joint diseases, particularly osteoporosis. It is also effective for bone strengthening when taken by growing school children.

[Brief description of drawings]

FIG. 1 is a graph showing the measurement results of bone strength when varying the blending amount of milk-derived basic protein in Test Example 1.

FIG. 2 is a graph showing the measurement results of bone strength when varying the blending amount of calcium carbonate or milk-derived calcium in Test Example 2.

FIG. 3 is a graph showing the bone strength measurement results when dry powder of drinking milk containing a milk-derived basic protein was added to the feed in Test Example 3.

FIG. 4 is a graph showing the bone strengths in Test Example 4 in which a fixed amount of basic protein derived from milk was blended, calcium carbonate and calcium derived from milk were blended simultaneously, and the respective amounts were changed. It is a graph which shows a measurement result.

FIG. 5 is a graph showing the measurement results of bone strength when the yogurt containing basic protein was mixed in the feed in Test Example 5.

FIG. 6 is a graph showing the measurement results of bone strength when the processed cheese to which the basic protein concentrate was added was mixed into the feed in Test Example 6.

FIG. 7 is a graph showing the results of measurement and comparison of bone strength when calcium carbonate, beef bone meal, and process cheese were added to the feed as the calcium source in Comparative Example 1.

FIG. 8 shows, as a calcium source in Comparative Example 2,
It is a graph which shows the measurement comparison result of the bone strength when yogurt powder and milk-derived calcium are added thereto and when milk-derived calcium is further added to the diet with a basic protein fraction derived from milk.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI Technical indication location A23C 19/00 A23L 1/30 A A61K 38/23 C07K 1/18 8318-4H 14/47 14 / 65 8318-4H // A61K 35/20 7431-4C (A61K 38/16 ABJ 35:20) (A61K 37/14 ABJ 35:20)

Claims (10)

[Claims] 1. A composition comprising a milk-derived basic protein fraction and milk-derived calcium, and having a bone-reinforcing action. 2. The composition according to claim 1, which is in the form of a preparation for oral administration. 3. The composition according to claim 1, which is in the form of a food product. 4. The composition according to claim 1, which is in the form of a beverage. 5. A milk-derived basic protein fraction of 50 mg / 100 g or more and a milk-derived calcium of 250 mg / 100 g or more are contained on a solid basis.
The composition according to any one of 1. 6. The composition according to claim 4, which contains 77 mg / 100 g or more of a milk-derived basic protein fraction and 380 mg / 100 g or more of milk-derived calcium in terms of solids. 7. The composition according to claim 1, wherein the basic protein fraction derived from milk contains 15% by weight or more of basic amino acids in the amino acid composition. 8. The composition according to claim 1, wherein the milk-derived basic protein fraction contains insulin-like growth factor-1. 9. The composition according to claim 8, wherein the milk-derived basic protein fraction contains 200 μg / 100 g or more of insulin-like growth factor-1 in terms of solid. 10. A milk-derived basic protein fraction is a fraction obtained by contacting milk or a milk-derived raw material with a cation exchange resin and then eluting with a solution having a salt concentration of 0.1 to 1.0 M. The composition according to any one of claims 1 to 9.