JP2516794B2 - Baby formula containing vitamin D metabolites - Google Patents

Description

TECHNICAL FIELD The present invention relates to a infant formula containing a vitamin D metabolite involved in normal bone growth, cell proliferation, regulation of immune function, etc. of infants. .

(Prior Art) Baby formulas are roughly classified into baby formulas and liquid artificial formulas for baby.As formulas for infants, formulas for infants, formulas for premature infants, follow-up formulas, special formulas for medical treatment and Others include milk powder used for artificial feeding of infants. Further, the liquid artificial milk for childcare is a liquid artificial milk prepared for the purpose of artificial nursing of infants.

Vitamin D is converted into 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 23,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D and 25,26-dihydroxyvitamin D in vivo. Is metabolized.

25-Hydroxy Vitamin D, 1.25-
Dihydroxyvitamin D is called active vitamin D, and plays an important role in maintaining homeostasis of calcium and phosphorus. In particular, 1.25-hydroxyvitamin D is known to have an important action on cell proliferation, cell differentiation, immune response regulation, fatty acid, prostaglandin and polyamine metabolism.

For developing infants, bone development and development of other physiological functions have important significance. Therefore, these functions of active vitamin D are considered to be extremely important for infants. Especially in premature babies and newborn babies, the incidence is high, and the significance is even greater.

On the other hand, despite being the same vitamin D metabolite,
-Little research has been done so far on dihydroxyvitamin D, 24 / 25-dihydroxyvitamin D, and 25 / 26-dihydroxyvitamin D, and what action they have in vivo. , Still unknown.

(Problems to be Solved by the Invention) When the present inventors measured vitamin D metabolites in breast milk, the results were 25 hydroxyvitamin D, 1,25-dihydroxyvitamin D, 23,25-dihydroxyvitamin D, 24. 25-dihydroxyvitamin D, and 25-26-
I found that dihydroxyvitamin D is relatively abundant. Especially, it has not been studied so far23.
I thought that the large amount of 25-dihydroxyvitamin D, 24.25-dihydroxyvitamin D, and 25.26-dihydroxyvitamin D might have some significance for infants, and conducted an intensive study.

The present inventors have measured and compared the content of vitamin D metabolites in human milk and commercially available infant formula, and as a result, vitamin D metabolites in human milk are respectively 25 hydroxyvitamin D 50 to 5000 ng / ml 1. 25-dihydroxyvitamin D 0.5 to 500ng / ml 23.5-dihydroxyvitamin D 1 to 500ng / ml 24.25-dihydroxyvitamin D 5 to 500ng / ml 25.26-dihydroxyvitamin D 1 to 500ng / Although it was present in the commercial infant formula, all vitamin D metabolites were found to be below the detection limit. It is considered that this is because most of the fats and oils in the commercially available infant formula are replaced with vegetable fats and oils.

The reason why breast-fed infants have better calcium absorption than artificially-fed infants may be because vitamin D metabolites are deficient in the marketed infant formula. When the products were blended, it was found that the vitamin D metabolite blend promotes the absorption of calcium, and the present invention was completed.

(Means for Solving the Problem) The infant formula, the infant formula containing phosphorus and calcium in the composition of the present invention, is mixed with a vitamin D metabolite.

In addition, the infant formula according to the present invention contains 25 hydroxyvitamin D, 1,25-dihydroxyvitamin D, 23,25-dihydroxyvitamin D, as vitamin D metabolites.
At least one selected from 24.25-dihydroxyvitamin D and 25.26-dihydroxyvitamin D is blended.

Especially, 23 ・ 25-dihydroxyvitamin D, 24 ・ 25
-The functions of dihydroxyvitamin D and 25 · 26-dihydroxyvitamin D are important, and the effects are greater when they are included and when they are not included. It has become possible to have a calcium absorption effect. Furthermore, it was revealed that each of these alone promotes calcium absorption.

It was also clarified that the presence of a certain amount of calcium and phosphorus is essential for these vitamin D metabolites to exert a calcium absorption effect.

As the phosphorus, dairy raw materials such as whey, diammonium phosphate, triammonium phosphate, monopotassium phosphate, dipotassium phosphate, tripotassium phosphate, tricalcium phosphate and the like can be used.

As calcium, calcium carbonate, calcium chloride, calcium hydroxide, calcium citrate, tricalcium phosphate, calcium lactate or the like can be used.

In this case, effective amounts of vitamin D metabolites, calcium and phosphorus are 25 hydroxyvitamin D 55 ng or more 1.25-dihydroxyvitamin D 0.5 ng or more 23.25-dihydroxyvitamin D per 100 g of milk solids prepared. 0.5 ng or more 24 ・ 25-dihydroxyvitamin D 5 ng or more 25 ・ 26-dihydroxyvitamin D 0.5 ng or more Calcium 33 mg or more Phosphorus 26 mg or more, and more preferably 25 hydroxyvitamin D 277 to 42000 ng 1.25- Dihydroxyvitamin D 2.7 to 4200ng 23 ・ 25-dihydroxyvitamin D 2.7 to 4200ng 24 ・ 25-dihydroxyvitamin D 27 to 4200ng 25 ・ 26-dihydroxyvitamin D 2.7 to 1200ng Calcium 65 to 1300mg Phosphorus 50 to 1000mg .

The vitamin D metabolite according to the present invention may be obtained by any method such as chemical synthesis, cell culture, extraction of natural products from fish oil and the like.

(Example) Hereinafter, the present invention will be specifically described based on Examples.

Example 1 Male Wistar rats of about 15 days old are divided into 7 groups of 7 groups [A, B, C, D, E, F, G].

Group A is a commercially available formula, Group B is a commercially available formula, and 3800 ng of 25 hydroxyvitamin D and 46 ng of 25-dihydroxyvitamin D are added to 100 g of each milk powder. Group B is a trial-prepared powdered milk with 380 ng of 23.25-dihydroxyvitamin D added to 100 g of vitamin D metabolite powdered milk, and Group D is a trial-prepared powdered milk of Group B with 100 g of vitamin metabolite powdered milk 380 ng of 24.25-dihydroxyvitamin D was added per trial, group E was a trial production of group B, and 380 ng of 25.26-dihydroxyvitamin D per 100 g of vitamin D metabolite powder was added to trial production. Formulated milk powder, F group as trial preparation milk powder of group B, and further 380 ng of 23.25-dihydroxyvitamin D and 380 ng of 24.25-dihydro per 100 g of vitamin D metabolite powdered milk At shea Vitamin D and 25-26-di-hydroxy vitamin D prototype formula milk supplemented with the 380Ng, respectively feeding 13% milk formula was feeding the G group by human breast milk. After feeding up to 6 weeks, the calcium concentration in plasma was measured.

As a result, Group A averaged 8.8 mg / dl, Group B averaged 10.4 mg / dl, Group C averaged 11.1 mg / dl, Group D averaged 11.0 mg / dl, Group E averaged 10.9 mg / dl, Group F The average was 10.9 mg / dl in the G group, and the average was 10.8 mg / dl in the G group. Moreover, the C group containing 23.25-dihydroxyvitamin D, the D group containing 25.25-dihydroxyvitamin D, and the E group containing 25.26-dihydroxyvitamin D were better than the B group not containing them. The effect was even greater and showed an absorption effect equivalent to that of the G group of breast milk feeding.

Example 2 Wistar rats of about 15 days old were divided into 4 groups (A, B, C, D) each having 10 rats and fed with the test feed.

The test feed was prepared with 12 g of casein, 13 g of whey concentrate powder, 5 g of corn salad oil, 6 g of α-starch, 62 g of minerals, 4 g of minerals, 1 g of cellulose, and 3 g of cellulose per 100 g of feed. Minerals, vitamins and methionine were added to this. The blending ratio was in accordance with AIN-76 (National Institute of Nutrition, White Mouse or Mouse Standard Purified Feed 1977). (The calcium content of this standard purified feed for mice is 520 mg / 100 g, and the phosphorus content is 400 mg / 100 g.) This was used as a control feed.

Group A was fed with a control feed, group B was a control feed, and 380 ng of 23.25-dihydroxyvitamin D was added, group C was a control feed, and 380 ng of 24.25-dihydroxyvitamin D was added. Was added to the group D as a control diet and 380 ng of 25.26-dihydroxyvitamin D was added to the group D as a control diet.

After breeding until 6 weeks of age, the calcium concentration in plasma was measured.

As a result, the average of the group A was 8.3 mg / dl, the average of the group B was 10.7 mg / dl, the average of the group C was 10.1 mg / dl, the average of the group D was 10.2 mg / dl, and 23 ・ 25-dihydroxyvitamin D, and 24 ・ 25−
It was revealed that dihydroxyvitamin D and 25 · 26-dihydroxyvitamin D promote calcium absorption even under a single condition without other vitamin D metabolites.

Example 3 35 Wistar male rats around 15 days old were divided into 5 groups (A, B, C, D, E) of 7 groups each, and the test feed had the same composition as in Example 2. Furthermore, 3800 ng of 25 hydroxyvitamin D was further added, and this was used as a test feed.

As a base, the feeds were prepared by adding the amounts of calcium and phosphorus shown in Table 1 for each group. Table 1 Group ABCD E Calcium 32 65 130 260 520 Phosphorus 25 50 100 200 400 (mg amount per 100 g) These After breeding for 6 weeks, the calcium concentration in plasma was measured.

 As a result, the average in Group A was 8.0 mg / dl, the average in Group B was 8.4 mg / dl, the average in Group C was 8.9 mg / dl, the average in Group D was 8.8 mg / dl, and the average in Group E was 9.1 mg / dl. It was

Example 4 35 Wistar male rats around 15 days old were divided into 5 groups (A, B, C, D, E) of 7 groups each, and the test feed had the same composition as in Example 2. Used, in addition, 46ng of 1.25
-Dihydroxyvitamin D was added and this test feed served as a control feed.

As a base, as in Example 3, for each group the above Table 1
A feed containing the amounts of calcium and phosphorus shown in (1) was prepared.

After breeding for 6 weeks by using these feeds, the calcium concentration in plasma was measured.

 As a result, the average in Group A was 8.1 mg / dl, the average in Group B was 8.4 mg / dl, the average in Group C was 9.0 mg / dl, the average in Group D was 9.3 mg / dl, and the average in Group E was 9.2 mg / dl. It was

Example 5 Thirty-five Wistar male rats around 15 days old were divided into 5 groups (A, B, C, D, E) of 7 groups each, and the test feed had the same composition as in Example 2. In addition, 3800 ng of 25 hydroxyvitamin D and 46 ng of 1.25-dihydroxyvitamin D were added, and this test feed was used as a control feed.

As a base, as in Example 3, for each group the above Table 1
A feed containing the amounts of calcium and phosphorus shown in (1) was prepared.

After breeding for 6 weeks by using these feeds, the calcium concentration in plasma was measured.

 As a result, the average of A group was 8.0 mg / dl, the average of B group was 8.5 mg / dl, the average of C group was 9.1 mg / dl, the average of D group was 9.6 mg / dl, and the average of E group was 10.1 mg / dl. It was

Example 6 Thirty-five Wistar male rats around 15 days old were divided into 5 groups (A, B, C, D, E) of 7 groups each, and the test feed had the same composition as in Example 2. In addition, 3800 ng of 25 hydroxyvitamin D, 46 ng of 1.25-dihydroxyvitamin D and 380 ng of 23.25-dihydroxyvitamin D were added, and this test feed was used as a control feed.

As a base, as in Example 3, for each group the above Table 1
A feed containing the amounts of calcium and phosphorus shown in (1) was prepared.

After breeding for 6 weeks by using these feeds, the calcium concentration in plasma was measured.

 As a result, the average of A group was 8.2 mg / dl, the average of B group was 9.4 mg / dl, the average of C group was 10.6 mg / dl, the average of D group was 10.8 mg / dl, and the average of E group was 11.2 mg / dl. It was

Example 7 35 Wistar male rats around 15 days old were divided into 5 groups (A, B, C, D, E) of 7 groups each, and the test feed had the same composition as in Example 2. In addition, 3800 ng of 25 hydroxyvitamin D, 46 ng of 1.25-dihydroxyvitamin D and 380 ng of 24.25-dihydroxyvitamin D were added, and this test feed was used as a control feed.

As a base, as in Example 3, for each group the above Table 1
A feed containing the amounts of calcium and phosphorus shown in (1) was prepared.

After breeding for 6 weeks by using these feeds, the calcium concentration in plasma was measured.

 As a result, the average of A group was 8.1 mg / dl, the average of B group was 9.1 mg / dl, the average of C group was 10.0 mg / dl, the average of D group was 10.5 mg / dl, and the average of E group was 10.7 mg / dl. It was

Example 8 35 male Wistar rats around 15 days old were divided into 5 groups (A, B, C, D, E) of 7 groups each, and the test feed had the same composition as in Example 2. In addition, 3800 ng of 25 hydroxyvitamin D, 46 ng of 1.25-dihydroxyvitamin D and 380 ng of 25.26-dihydroxyvitamin D were added, and this test feed was used as a control feed.

As a base, as in Example 3, for each group the above Table 1
A feed containing the amounts of calcium and phosphorus shown in (1) was prepared.

After breeding for 6 weeks by using these feeds, the calcium concentration in plasma was measured.

 As a result, the average of A group was 8.2 mg / dl, the average of B group was 8.9 mg / dl, the average of C group was 10.2 mg / dl, the average of D group was 10.4 mg / dl, and the average of E group was 10.9 mg / dl. It was

From Examples 3 to 8, it became clear that certain amounts of calcium and phosphorus are required for these vitamin D metabolites to exert the effect of promoting calcium absorption.

Comparative Example 35 Wistar male rats around 15 days old were divided into 5 groups (A, B, C, D, E) of 7 groups each, and the test feed had the same composition as in Example 2. I was there. In this comparative example, as a base without addition of the vitamin D metabolite, a feed was prepared for each group to which the calcium and phosphorus blending amounts shown in Table 1 were added, as in Example 3.

After breeding for 6 weeks by using these feeds, the calcium concentration in plasma was measured.

 As a result, the average in Group A was 7.9 mg / dl, the average in Group B was 7.9 mg / dl, the average in Group C was 8.1 mg / dl, the average in Group D was 8.0 mg / dl, and the average in Group E was 8.2 mg / dl. It was

(Effects of the Invention) According to the present invention, the addition of vitamin D metabolites promotes the absorption of calcium, and a certain amount of calcium and phosphorus are required for the vitamin D metabolites to exert the effect of promoting calcium absorption. It was found that, because the vitamin D metabolite was added to the infant formula containing calcium and phosphorus, the formula was able to exert a calcium absorption promoting effect more comparable to that of breast milk.

Claims (2)

(57) [Claims] 1. A baby formula prepared by blending a vitamin D metabolite with a baby formula containing calcium and phosphorus in the composition. 2. As a vitamin D metabolite, 25 hydroxyvitamin D, 1,25-dihydroxyvitamin D, 23.
The infant formula according to claim 1, which comprises at least one selected from 25-dihydroxyvitamin D, 24.25-dihydroxyvitamin D and 25.26-dihydroxyvitamin D.