JP2516794C - - Google Patents
Info
- Publication number
- JP2516794C JP2516794C JP2516794C JP 2516794 C JP2516794 C JP 2516794C JP 2516794 C JP2516794 C JP 2516794C
- Authority
- JP
- Japan
- Prior art keywords
- group
- dihydroxyvitamin
- calcium
- vitamin
- averaged
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- OYPRJOBELJOOCE-UHFFFAOYSA-N calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 39
- 239000011575 calcium Substances 0.000 claims description 39
- 229910052791 calcium Inorganic materials 0.000 claims description 39
- 229940046008 Vitamin D Drugs 0.000 claims description 28
- 229930003316 Vitamin D Natural products 0.000 claims description 28
- 235000019166 vitamin D Nutrition 0.000 claims description 28
- 239000011710 vitamin D Substances 0.000 claims description 28
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 28
- 235000013350 formula milk Nutrition 0.000 claims description 24
- 239000002207 metabolite Substances 0.000 claims description 23
- OAICVXFJPJFONN-UHFFFAOYSA-N phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 19
- 239000011574 phosphorus Substances 0.000 claims description 19
- 229910052698 phosphorus Inorganic materials 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 12
- 229960005069 Calcium Drugs 0.000 description 38
- 235000001465 calcium Nutrition 0.000 description 38
- 210000004080 Milk Anatomy 0.000 description 17
- 235000013336 milk Nutrition 0.000 description 17
- 239000008267 milk Substances 0.000 description 17
- 239000000843 powder Substances 0.000 description 14
- JWUBBDSIWDLEOM-DTOXIADCSA-N Calcifediol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)CCC1=C JWUBBDSIWDLEOM-DTOXIADCSA-N 0.000 description 12
- 235000021318 Calcifediol Nutrition 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 11
- 238000010521 absorption reaction Methods 0.000 description 10
- 210000002381 Plasma Anatomy 0.000 description 9
- 230000001488 breeding Effects 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 235000020256 human milk Nutrition 0.000 description 7
- 210000004251 Milk, Human Anatomy 0.000 description 6
- 241000700157 Rattus norvegicus Species 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- WWGCQHXFACVYPT-JKVVTCAUSA-N 25,26-dihydroxyvitamin D Chemical compound C([C@@H]1CC[C@@H]([C@]1(CC1)C)[C@@H](CCCC(C)(O)CO)C)\C1=C/C=C1/C[C@@H](O)CCC1=C WWGCQHXFACVYPT-JKVVTCAUSA-N 0.000 description 4
- 235000020940 control diet Nutrition 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- FCKJYANJHNLEEP-OIMXRAFZSA-N 24,25-Dihydroxyvitamin D Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCC(O)C(C)(C)O)C)=C\C=C1\C[C@H](O)CCC1=C FCKJYANJHNLEEP-OIMXRAFZSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- 230000035764 nutrition Effects 0.000 description 3
- 230000001737 promoting Effects 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 229930003231 vitamins Natural products 0.000 description 3
- 210000000481 Breast Anatomy 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H Tricalcium phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 229940029983 VITAMINS Drugs 0.000 description 2
- 229940021016 Vitamin IV solution additives Drugs 0.000 description 2
- 239000005862 Whey Substances 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 230000000474 nursing Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 229940078499 tricalcium phosphate Drugs 0.000 description 2
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 2
- 235000019731 tricalcium phosphate Nutrition 0.000 description 2
- GMRQFYUYWCNGIN-ZVUFCXRFSA-N 1,25-dihydroxy vitamin D3 Chemical compound C1([C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=CC=C1C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-ZVUFCXRFSA-N 0.000 description 1
- ZRIUUUJAJJNDSS-UHFFFAOYSA-N Ammonium phosphates Chemical compound [NH4+].[NH4+].[NH4+].[O-]P([O-])([O-])=O ZRIUUUJAJJNDSS-UHFFFAOYSA-N 0.000 description 1
- 210000000988 Bone and Bones Anatomy 0.000 description 1
- 229960003563 Calcium Carbonate Drugs 0.000 description 1
- 229960004256 Calcium Citrate Drugs 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H Calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L Calcium hydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L Calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000005696 Diammonium phosphate Substances 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L Dipotassium phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 230000036740 Metabolism Effects 0.000 description 1
- 230000035633 Metabolized Effects 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M Monopotassium phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 240000004668 Valerianella locusta Species 0.000 description 1
- 235000003560 Valerianella locusta Nutrition 0.000 description 1
- 229940088594 Vitamin Drugs 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 230000014461 bone development Effects 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L cacl2 Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229960002713 calcium chloride Drugs 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 229940095643 calcium hydroxide Drugs 0.000 description 1
- 235000011116 calcium hydroxide Nutrition 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 229910000388 diammonium phosphate Inorganic materials 0.000 description 1
- 235000019838 diammonium phosphate Nutrition 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000035786 metabolism Effects 0.000 description 1
- 235000006109 methionine Nutrition 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 239000005445 natural product Substances 0.000 description 1
- 229930014626 natural products Natural products 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 235000008476 powdered milk Nutrition 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Description
【発明の詳細な説明】
【産業上の利用分野】
本発明は、乳児の骨の正常発育、細胞増殖、免疫機能の制御等にかかわるビタ
ミンＤ代謝産物を配合した育児用調製乳に関するものである。
【従来の技術】
育児用調製乳は、育児用粉乳及び育児用液体人工乳に大別され、育児用粉乳と
しては、乳児用調製粉乳、未熟児用粉乳、フォローアップミルク、医療用特殊粉
乳及びその他乳児の人工哺育に用いる粉乳類を包含する。また、育児用液体人工
乳としては、乳児の人工哺育を目的として調製した液状の人工乳である。
ビタミンＤは、生体内で２５−ハイドロキシビタミンＤ、１・２５−ジハイド
ロキシビタミンＤ、２３・２５−ジハイドロキシビタミンＤ、２４・２５−ジハ
イドロキシビタミンＤ及び２５・２６−ジハイドロキシビタミンＤ等に代謝され
る。
これらのうち２５−ハイドロキシビタミンＤ、１・２５−ジハイドロキシビタ
ミンＤは、活性型ビタミンＤと呼ばれ、カルシウムやリンのホメオスタシス維持
に重要な役割を果している。とくに１・２５−ハイドロキシビタミンＤは細胞増
殖、細胞分化、免疫応答制御、脂肪酸、プロスタグランジン、ポリアミン代謝に
も重要な作用を持つことが知られている。
発育途上の乳児にとって、骨発達、他の生理機能の発育は重要な意義を持って
いる。そのため活性型ビタミンＤのこれらの機能は乳児にとって極めて重要なも
のと考えられる。とくに未熟児、新生児においては、佝僂病等の発症率が高いた
めその意義は更に大きい。
一方、同じビタミンＤ代謝産物でありながら、２３・２５−ジハイドロキシビ
タミンＤ、２４・２５−ジハイドロキシビタミンＤ、２５・２６−ジハイドロキ
シビタミンＤについては、これ迄ほとんど研究が進んでおらず、それらが生体内
でどのような作用を持っているのか、未だ不明のままである。
【発明が解決しようとする課題】
本発明者らが母乳中のビタミンＤ代謝産物を測定したところ、２５ハイドロキ
シビタミンＤ、１・２５−ジハイドロキシビタミンＤ、２３・２５−ジハイドロ
キシビタミンＤ、２４・２５−ジハイドロキシビタミンＤ、及び２５・２６−ジ
ハイドロキシビタミンＤが、比較的多く存在していることを知った。とくに、こ
れまで研究されていない２３・２５−ジハイドロキシビタミンＤ、２４・２５−
ジハイドロキシビタミンＤ、２５・２６−ジハイドロキシビタミンＤの量が多い
ことは乳児にとって何らかの意養を持つのではないかと考え、鋭意研究した。
本発明者らは人乳と市販乳児用調製粉乳中のビタミンＤ代謝産物含量を測定比
較した結果、人乳中にはビタミンＤ代謝産物が、それぞれ、
２５ハイドロキシビタミンＤ 50〜5000ng/ml
１・２５−ジハイドロキシビタミンＤ 0.5〜500ng/ml
２３・２５−ジハイドロキシビタミンＤ 1〜500ng/ml
２４・２５−ジハイドロキシビタミンＤ 5〜500ng/ml
２５・２６−ジハイドロキシビタミンＤ 1〜500ng/ml
存在していたが、市販乳児用調製粉乳中はいずれのビタミンＤ代謝産物も検出限
界以下であることが判った。これは市販乳児用調製粉乳の油脂が大部分、植物油
脂に置換されていることなどによると考えられた。
母乳栄養児が人工栄養児に比べてカルシウム吸収がよいのは、このように市販
乳児用調製粉乳にビタミンＤ代謝産物が欠損しているためではないかと考え、市
販乳児用調製粉乳にビタミンＤ代謝産物を配合したところ、ビタミンＤ代謝産物
配合がカルシウムの吸収を促進することを認め、本発明を完成した。
【課題を解決するための手段】
本発明の育児用調製乳は、組成物中にリン及びカルシウムを含有する育児用調
製乳に対して、ビタミンＤ代謝産物として、２３・２５−ジハイドロキシビタミ
ンＤ、２４・２５−ジハイドロキシビタミンＤ及び２５・２６−ジハイドロキシ
ビタミンＤの中から選択された一種以上を配合して成る。
また、本発明の育児用調製乳は、前記育児用調製乳に、さらに、２５ハイドロ
キシビタミンＤ及び／又は１・２５−ジハイドロキシビタミンＤを配合して成る
。
とくに、２３・２５−ジハイドロキシビタミンＤ、２４・２５−ジハイドロキ
シビタミンＤ、２５・２６−ジハイドロキシビタミンＤの働きは重要で、これら
を含む場合は含まない場合よりも効果が大きく、これらのビタミンＤを配合する
ことによって、人工栄養でも母乳栄養なみのカルシウムの吸収効果を持たせるこ
とが可能となった。さらに、これらはそれぞれ単独でもカルシウム吸収を促進す
ることが明らかとなった。
また、これらのビタミンＤ代謝産物がカルシウム吸収効果を発揮するためには
一定量のカルシウム、リンの存在が必須であることも明らかとなった。
リンとしては、ホエー等の乳原料由来のもの、リン酸二アンモニウム、リン酸
三アンモニウム、リン酸一カリウム、リン酸二カリウム、リン酸三カリウム、リ
ン酸三カルシウム等が使用できる。
カルシウムとしては、炭酸カルシウム、塩化カルシウム、水酸化カルシウム、
クエン酸カルシウム、リン酸三カルシウム、乳酸カルシウム等が使用できる。
この場合のビタミンＤ代謝産物、カルシウム、リンの効果的配合量は調製乳固
形分100gあたり、
２５ハイドロキシビタミンＤ 55ng以上
１・２５−ジハイドロキシビタミンＤ 0.5ng以上
２３・２５−ジハイドロキシビタミンＤ 0.5ng以上
２４・２５−ジハイドロキシビタミンＤ 5ng以上
２５・２６−ジハイドロキシビタミンＤ 0.5ng以上
カルシウム 33mg以上
リン 26mg以上
であり、さらに好ましくは
２５ハイドロキシビタミンＤ 277〜42000ng
１・２５−ジハイドロキシビタミンＤ 2.7〜4200ng
２３・２５−ジハイドロキシビタミンＤ 2.7〜4200ng
２４・２５−ジハイドロキシビタミンＤ 27〜4200ng
２５・２６−ジハイドロキシビタミンＤ 2.7〜1200ng
カルシウム 65〜1300mg
リン 50〜1000mg
である。
なお、本発明にかかわるビタミンＤ代謝産物は、化学合成、細胞培養、魚油等
からの天然物抽出その他、いずれの方法により得たものでも構わない。
【実施例】
以下、実施例に基づき本発明を具体的に説明する。
実施例１
日令１５日前後のウィスター系雄ラットにつき各群７匹を７群（Ａ、Ｂ、Ｃ、
Ｄ、Ｅ、Ｆ、Ｇ）に分ける。
Ａ群を市販調製乳、
Ｂ群を市販調製乳にビタミンＤ代謝産物をそれぞれの粉乳100gあたり、3800ng
の２５ハイドロキシビタミンＤ及び46ngの１・２５−ジハイドロキシビタミンＤ
を添加した試作調製粉乳、
Ｃ群をＢ群の試作調製粉乳にさらにビタミンＤ代謝産物粉乳100gあたり380ng
の２３・２５−ジハイドロキシビタミンＤを添加した試作調製粉乳、
Ｄ群をＢ群の試作調製粉乳にさらにビタミン代謝産物粉乳100gあたり380ngの
２４・２５−ジハイドロキシビタミンＤを添加した試作調製粉乳、
Ｅ群をＢ群の試作調製粉乳にさらにビタミンＤ代謝産物粉乳100gあたり380ng
の２５・２６−ジハイドロキシビタミンＤを添加した試作調製粉乳、
Ｆ群をＢ群の試作調製粉乳にさらにビタミンＤ代謝産物粉乳100gあたり380ng
の２３・２５−ジハイドロキシビタミンＤ、380ngの２４・２５−ジハイドロキ
シビタミンＤ及び380ngの２５・２６−ジハイドロキシビタミンＤを添加した試
作調製粉乳にて、それぞれ13%調乳で哺乳し、Ｇ群を人の母乳にて哺乳した。６
週令まで哺乳後、血漿中のカルシウム濃度を測定した。
その結果、
Ａ群で平均 8.8mg/dl、
Ｂ群で平均 10.4mg/dl、
Ｃ群で平均 11.1mg/dl、
Ｄ群で平均 11.0mg/dl、
Ｅ群で平均 10.9mg/dl、
Ｆ群で平均 10.9mg/dl、
Ｇ群で平均 10.8mg/dlとなり、
Ｂ、Ｃ、Ｄ、Ｅ、Ｆ群とも母乳栄養なみのカルシウム吸収性を示した。しかも２
３・２５−ジハイドロキシビタミンＤを含むＣ群、および２４・２５−ジハイド
ロキシビタミンＤを含むＤ群、および２５・２６−ジハイドロキシビタミンＤを
含むＥ群の方が、含まないＢ群よりもさらに効果が大きく、母乳栄養のＧ群と同
等の吸収効果を示した。
実施例２
日令１５日前後のウィスター系ラットを各群１０匹の４群（Ａ、Ｂ、Ｃ、Ｄ）
に分け、試験飼料にて飼育した。
試験飼料は飼料100gあたり、
カゼイン 12g
ホエーコンセントレイト粉 13g
コーンサラダ油 5g
α−でんぷん 62g
ミネラル 4g
ビタミン 1g
セルロース 3g
にて調製した。これにミネラル、ビタミン、メチオニンを配合した。この配合比
はAIN-76（米国国立栄養研究所、白ネズミあるいはマウス用標準精製飼料1977）
に従った。（尚、このマウス用標準精製飼料のカルシウム含量は、520mg/100gで
、
リンの含量は、400mg/100gである。）これを対照飼料とした。
Ａ群を対照飼料にて飼育し、
Ｂ群を対照飼料に、380ngの２３・２５−ジハイドロキシビタミンＤを添加した
飼料で、
Ｃ群を対照飼料に、380ngの２４・２５−ジハイドロキシビタミンＤを添加した
飼料で、
Ｄ群を対照飼料に、380ngの２５・２６−ジハイドロキシビタミンＤを添加した
飼料で、それぞれ飼育した。
６週令まで飼育後、血漿中のカルシウム濃度を測定した。
その結果、
Ａ群で平均 8.3mg/dl、
Ｂ群で平均 10.7mg/dl、
Ｃ群で平均 10.1mg/dl、
Ｄ群で平均 10.2mg/dlとなり、
２３・２５−ジハイドロキシビタミンＤ、および２４・２５−ジハイドロキシ
ビタミンＤ、および２５・２６−ジハイドロキシビタミンＤが他のビタミンＤ代
謝産物のない単独条件下においてもカルシウムの吸収を促進することが明らかと
なった。比較例１
日令１５日前後のウィスター系雄ラット３５匹を各群７匹の５群（Ａ、Ｂ、Ｃ
、Ｄ、Ｅ）に分け、試験飼料は実施例２と同じ配合のものを用い、さらに、3800
ngの２５ハイドロキシビタミンＤを添加し、これを試験飼料とした。
ベースとして、各群用に表１に示すカルシウム、リン配合量を加え飼科を作成
した。
【表１】
これらの飼料にて６週令まで飼育後、血漿中のカルシウム濃度を測定した。
その結果、
Ａ群で平均 8.0mg/dl、
Ｂ群で平均 8.4mg/dl、
Ｃ群で平均 8.9mg/dl、
Ｄ群で平均 8.8mg/dlとなり、
Ｅ群で平均 9.1mg/dlとなった。比較例２
日令１５日前後のウィスター系雄ラット３５匹を各群７匹の５群（Ａ、Ｂ、Ｃ
、Ｄ、Ｅ）に分け、試験飼料は実施例２と同じ配合のものを用い、さらに、46ng
の１・２５−ジハイドロキシビタミンＤを添加し、この試験飼料を対照飼料とし
た。
ベースとして、比較例１と同様に、各群用に前記表１に示すカルシウム、リン
配合量を加えた飼料を作成した。
これらの飼料にて６週令まで飼育後、血漿中のカルシウム濃度を測定した。
その結果、
Ａ群で平均 8.1mg/dl、
Ｂ群で平均 8.4mg/dl、
Ｃ群で平均 9.0mg/dl、
Ｄ群で平均 9.3mg/dlとなり、
Ｅ群で平均 9.2mg/dlとなった。比較例３
日令１５日前後のウィスター系雄ラット３５匹を各群７匹の５群（Ａ、Ｂ、Ｃ
、Ｄ、Ｅ）に分け、試験飼料は実施例２と同じ配合のものを用い、さらに、3800
ngの２５ハイドロキシビタミンＤと46ngの１・２５−ジハイドロキシビタミンＤ
を添加し、この試験飼料を対照飼料とした。
ベースとして、比較例１と同様に、各群用に前記表１に示すカルシウム、リン
配合量を加えて飼料を作成した。
これらの飼料にて６週令まで飼育後、血漿中のカルシウム濃度を測定した。
その結果、
Ａ群で平均 8.0mg/dl、
Ｂ群で平均 8.5mg/dl、
Ｃ群で平均 9.1mg/dl、
Ｄ群で平均 9.6mg/dlとなり、
Ｅ群で平均 10.1mg/dlとなった。
実施例３
日令１５日前後のウィスター系雄ラット３５匹を各群７匹の５群（Ａ、Ｂ、Ｃ
、Ｄ、Ｅ）に分け、試験飼料は実施例２と同じ配合のものを用い、さらに、3800
ngの２５ハイドロキシビタミンＤ、46ngの１・２５−ジハイドロキシビタミンＤ
及び380ngの２３・２５−ジハイドロキシビタミンＤを添加し、この試験飼料を
対照飼料とした。
ベースとして、比較例１と同様に、各群用に前記表１に示すカルシウム、リン
配合量を加えた飼料を作成した。
これらの飼料にて６週令まで飼育後、血漿中のカルシウム濃度を測定した。
その結果、
Ａ群で平均 8.2mg/dl
Ｂ群で平均 9.4mg/dl、
Ｃ群で平均 10.6mg/dl、
Ｄ群で平均 10.8mg/dlとなり、
Ｅ群で平均 11.2mg/dlとなった。
実施例４
日令１５日前後のウィスター系雄ラット３５匹を各群７匹の５群（Ａ、Ｂ、Ｃ
、Ｄ、Ｅ）に分け、試験飼料は実施例２と同じ配合のものを用い、さらに、3800
ngの２５ハイドロキシビタミンＤ、46ngの１・２５−ジハイドロキシビタミンＤ
及び380ngの２４・２５−ジハイドロキシビタミンＤを添加し、この試験飼料を
対照飼料とした。
ベースとして、比較例１と同様に、各群用に前記表１に示すカルシウム、リン
配合量を加えた飼料を作成した。
これらの飼料にて６週令まで飼育後、血漿中のカルシウム濃度を測定した。
その結果、
Ａ群で平均 8.1mg/dl、
Ｂ群で平均 9.1mg/dl、
Ｃ群で平均 10.0mg/dl、
Ｄ群で平均 10.5mg/dlとなり、
Ｅ群で平均 10.7mg/dlとなった。
実施例５
日令１５日前後のウィスター系雄ラット３５匹を各群７匹の５群（Ａ、Ｂ、Ｃ
、Ｄ、Ｅ）に分け、試験飼料は実施例２と同じ配合のものを用い、さらに、3800
ngの２５ハイドロキシビタミンＤ、46ngの１・２５−ジハイドロキシビタミンＤ
及び380ngの２５・２６−ジハイドロキシビタミンＤを添加し、この試験飼料を
対照飼料とした。
ベースとして、比較例１と同様に、各群用に前記表１に示すカルシウム、リン
配合量を加えた飼料を作成した。
これらの飼料にて６週令まで飼育後、血漿中のカルシウム濃度を測定した。
その結果、
Ａ群で平均 8.2mg/dl、
Ｂ群で平均 8.9mg/dl、
Ｃ群で平均 10.2mg/dl、
Ｄ群で平均 10.4mg/dlとなり、
Ｅ群で平均 10.9mg/dlとなった。
実施例３〜５より、これらビタミンＤ代謝産物がカルシウム吸収促進効果を発
揮するには一定量のカルシウム、リンが必要であることが明らかになった。
比較例４
日令１５日前後のウィスター系雄ラット３５匹を各群７匹の５群（Ａ、Ｂ、Ｃ
、Ｄ、Ｅ）に分け、試験飼料は実施例２と同じ配合のものを用いた。この比較例
においてはビタミンＤ代謝産物を添加せずにベースとして、比較例１と同様に、
各群用に前記表１に示すカルシウム、リン配合量を加えた飼料を作成した。
これらの飼科にて６週令まで飼育後、血漿中のカルシウム濃度を測定した。
その結果、
Ａ群で平均 7.9mg/dl、
Ｂ群で平均 7.9mg/dl、
Ｃ群で平均 8.1mg/dl、
Ｄ群で平均 8.0mg/dlとなり、
Ｅ群で平均 8.2mg/dlとなった。
【発明の効果】
本発明によれば、ビタミンＤ代謝産物配合がカルシウムの吸収を促進すると共
に、このビタミンＤ代謝産物がカルシウム吸収促進効果を発揮するには一定量の
カルシウム、リンが必要であることを見出し、カルシウム及びリンを含有する育
児用調製乳にビタミンＤ代謝産物を配合したので、調製乳が一層母乳に匹敵する
カルシウム吸収促進効果を発揮することが可能となった。Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an infant formula containing a vitamin D metabolite related to normal growth, cell proliferation, control of immune function, etc. of infant bone. . 2. Description of the Related Art Infant formulas are broadly classified into infant formulas and liquid formulas for infants. As infant formulas, formulas for infants, formulas for premature infants, follow-up formulas, special formulas for medical use and Others include powdered milk used for artificial nursing of infants. In addition, the liquid artificial milk for child care 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. Metabolized. Among them, 25-hydroxyvitamin D and 1 · 25-dihydroxyvitamin D are called active vitamin D and play an important role in maintaining calcium and phosphorus homeostasis. In particular, 1.25-hydroxyvitamin D is known to have an important effect on cell proliferation, cell differentiation, immune response control, fatty acid, prostaglandin, and polyamine metabolism. For developing babies, bone development and the development of other physiological functions are important. Therefore, these functions of active vitamin D are considered to be extremely important for infants. Particularly in premature babies and newborn babies, their significance is even greater because the incidence of useful diseases is high. On the other hand, although it is the same vitamin D metabolite, research on 23.25-dihydroxyvitamin D, 24.25-dihydroxyvitamin D, and 25.26-dihydroxyvitamin D has hardly progressed until now. What effects they have in vivo remains unknown. The present inventors measured vitamin D metabolites in breast milk, and found that 25 hydroxyvitamin D, 1 · 25-dihydroxyvitamin D, 23 · 25-dihydroxyvitamin D, 24 -I learned that 25-dihydroxyvitamin D and 25.26-dihydroxyvitamin D are present in relatively large amounts. In particular, 23.25-dihydroxyvitamin D, 24.25-
We thought that high amounts of dihydroxyvitamin D and 25,26-dihydroxyvitamin D might have some kind of nutrition for infants, and studied diligently. The present inventors measured and compared the content of vitamin D metabolites in human milk and commercial infant formula, and found that vitamin D metabolites in human milk contained 25-hydroxyvitamin D 50-5000 ng / ml 1. 25-dihydroxyvitamin D 0.5-500 ng / ml 23.25-dihydroxyvitamin D 1-500 ng / ml 24.25-dihydroxyvitamin D 5-500 ng / ml 25.26-dihydroxyvitamin D 1-500 ng / ml Although present, it was found that all vitamin D metabolites were below the detection limit in commercial infant formula. This was thought to be due to the fact that most of the fats and oils of the commercial infant formula were replaced with vegetable fats and oils. We believe that the reason why breast-fed infants absorb calcium better than artificial-fed infants may be due to the lack of vitamin D metabolites in commercial infant formulas. When the product was blended, it was recognized that the vitamin D metabolite blend promoted calcium absorption, and the present invention was completed. Means for Solving the Problems The infant formula of the present invention can be used as a vitamin D metabolite as a 23.25-dihydroxybitaminate with respect to a child formula containing phosphorus and calcium in the composition.
D, 24 • 25-dihydroxyvitamin D and 25 • 26-dihydroxy
It comprises one or more selected from vitamin D. In addition, the infant formula of the present invention further comprises 25
It comprises a mixture of xyvitamin D and / or 1.25-dihydroxyvitamin D. In particular, the function of 23.25-dihydroxyvitamin D, 24.25-dihydroxyvitamin D, and 25.26-dihydroxyvitamin D is important, and when they are contained, the effect is greater than when they are not contained. By adding vitamin D, it has become possible to provide an effect of absorbing calcium, which is comparable to that of breast milk even in artificial nutrition. Further, it was found that each of them alone promotes calcium absorption. It has also been found that the presence of certain amounts of calcium and phosphorus is essential for these vitamin D metabolites to exert their calcium absorption effect. As the phosphorus, those derived from milk 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 and the like can be used. In this case, the effective amount of the vitamin D metabolite, calcium and phosphorus is 25 ng or more of vitamin D 55 ng or more, and 1.25 or 25-dihydroxyvitamin D 0.5 ng or more. ng to 24,25-dihydroxyvitamin D 5 ng to 25,26-dihydroxyvitamin D 0.5 ng to calcium 33 mg to phosphorus 26 mg or more, more preferably 25 hydroxyvitamin D 277 to 42000 ng 1,25-dihydroxyvitamin D 2.7-4200 ng 23.25-dihydroxyvitamin D 2.7-4200 ng 24.25-dihydroxyvitamin D 27-4200 ng 25.26-dihydroxyvitamin D 2.7-1200 ng Calcium 65-1300 mg Phosphorus 50-1000 mg. The vitamin D metabolite according to the present invention may be obtained by any method such as chemical synthesis, cell culture, natural product extraction from fish oil and the like. Hereinafter, the present invention will be specifically described based on examples. Example 1 Seven groups of 7 males (A, B, C,
D, E, F, G). Group A: Commercially prepared milk; Group B: Commercially prepared milk with vitamin D metabolites 3800 ng per 100 g of milk powder
Of 25 hydroxyvitamin D and 46 ng of 1.25-dihydroxyvitamin D
380 ng / 100 g of vitamin D metabolite powder in addition to the prototype milk powder of Group B
A trial-prepared milk powder to which 23 · 25-dihydroxyvitamin D was added; a D-group was a trial-prepared milk powder obtained by further adding 380 ng of 24 · 25-dihydroxyvitamin D per 100 g of vitamin metabolite milk powder to the B-group experimental milk powder; Group E is added to the experimental milk powder of Group B, and 380 ng / 100 g of vitamin D metabolite milk powder
A trial milk powder to which 25 / 26-dihydroxyvitamin D was added, the group F was added to the milk powder of the trial group B, and 380 ng per 100 g of vitamin D metabolite milk powder
Of 23.25-dihydroxyvitamin D, 380 ng of 24,25-dihydroxyvitamin D and 380 ng of 25,26-dihydroxyvitamin D were added to each of the prepared milk powders, and each of them was breast-feeded at 13% formula. Groups were fed with human breast milk. 6
After feeding until the age of the week, the calcium concentration in the 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, and 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. All of the B, C, D, E, and F groups exhibited calcium absorption comparable to that of breast milk. Moreover, 2
Group C containing 3,25-dihydroxyvitamin D, Group D containing 24,25-dihydroxyvitamin D, and Group E containing 25,26-dihydroxyvitamin D are better than Group B without it. The effect was even greater and showed an absorption effect equivalent to that of group G for breastfeeding. Example 2 Wistar rats around 15 days old were divided into 4 groups (A, B, C, D) of 10 rats each.
And bred on a test feed. The test feed was prepared with 12 g of casein, 13 g of whey concentrate powder, 5 g of corn salad oil, 62 g of α-starch, 4 g of minerals, 1 g of vitamins, and 3 g of cellulose per 100 g of feed. Minerals, vitamins and methionine were added to this. This compounding ratio is AIN-76 (US National Institute of Nutrition, standard purified feed for white rats or mice 1977)
Followed. (The calcium content of the standard purified feed for mice was 520 mg / 100 g, and the phosphorus content was 400 mg / 100 g.) This was used as a control feed. Group A was bred on a control diet, Group B was a control diet and 380 ng of 23 • 25-dihydroxyvitamin D was added, and Group C was a control diet and 380 ng of 24 • 25-dihydroxyvitamin D was added. Group D was fed as a control diet and a diet supplemented with 380 ng of 25.26-dihydroxyvitamin D. After breeding until the age of 6 weeks, the calcium concentration in the plasma was measured. As a result, group A had an average of 8.3 mg / dl, group B had an average of 10.7 mg / dl, group C had an average of 10.1 mg / dl, group D had an average of 10.2 mg / dl, 23.25-dihydroxyvitamin D, and It has been shown that 24.25-dihydroxyvitamin D and 25.26-dihydroxyvitamin D promote calcium absorption even under sole conditions without other vitamin D metabolites. Comparative Example 1 35 male Wistar rats, 15 days old or around 15 days each, were divided into 5 groups of 7 rats (A, B, C).
, D, and E), and the test feed used had the same composition as that of Example 2, and 3800
ng of 25 hydroxyvitamin D was added and used as a test feed. As a base, the amounts of calcium and phosphorus shown in Table 1 were added for each group to create a family. [Table 1] After breeding on these feeds until the age of 6 weeks, the calcium concentration in the plasma was measured. As a result, group A averaged 8.0 mg / dl, group B averaged 8.4 mg / dl, group C averaged 8.9 mg / dl, group D averaged 8.8 mg / dl, and group E averaged 9.1 mg / dl. Was. COMPARATIVE EXAMPLE 2 Five groups of 35 Wistar male rats (7 days each, 15 days old, around 15 days old) (A, B, C)
, D, E), and the test feed used had the same composition as in Example 2 and was further supplemented with 46 ng.
1.25-dihydroxyvitamin D was added, and this test feed was used as a control feed. As a base, as in Comparative Example 1 , a feed was prepared for each group to which the amounts of calcium and phosphorus shown in Table 1 were added. After breeding on these feeds until the age of 6 weeks, the calcium concentration in the plasma was measured. As a result, group A averaged 8.1 mg / dl, group B averaged 8.4 mg / dl, group C averaged 9.0 mg / dl, group D averaged 9.3 mg / dl, and group E averaged 9.2 mg / dl. Was. COMPARATIVE EXAMPLE 3 35 male Wistar rats, 15 days old or about 15 days old, were divided into 5 groups of 7 rats each (A, B, C).
, D, and E), and the test feed used had the same composition as that of Example 2, and 3800
ng of 25-hydroxyvitamin D and 46 ng of 1.25-dihydroxyvitamin D
Was added, and this test feed was used as a control feed. As a base, as in Comparative Example 1 , a feed was prepared for each group by adding the amounts of calcium and phosphorus shown in Table 1 above. After breeding on these feeds until the age of 6 weeks, the calcium concentration in the plasma was measured. As a result, the average was 8.0 mg / dl for group A, 8.5 mg / dl for group B, 9.1 mg / dl for group C, 9.6 mg / dl for group D, and 10.1 mg / dl for group E. Was. Example 3 35 Wistar male rats around 15 days old were grouped into 7 groups, each consisting of 5 groups (A, B, C).
, D, and E), and the test feed used had the same composition as that of Example 2, and 3800
ng of 25-hydroxyvitamin D, 46 ng of 1.25-dihydroxyvitamin D
And 380 ng of 23 · 25-dihydroxyvitamin D, and the test feed was used as a control feed. As a base, as in Comparative Example 1 , a feed was prepared for each group to which the amounts of calcium and phosphorus shown in Table 1 were added. After breeding on these feeds until the age of 6 weeks, the calcium concentration in the plasma was measured. As a result, the average was 8.2 mg / dl in group A, 9.4 mg / dl in group B, 10.6 mg / dl in group C, 10.8 mg / dl in group D, and 11.2 mg / dl in group E. . Example 4 35 groups of male Wistar rats, 15 days old and 15 days old, were grouped into 5 groups of 7 (A, B, C).
, D, and E), and the test feed used had the same composition as that of Example 2, and 3800
ng of 25-hydroxyvitamin D, 46 ng of 1.25-dihydroxyvitamin D
And 380 ng of 24 · 25-dihydroxyvitamin D, and this test feed was used as a control feed. As a base, as in Comparative Example 1 , a feed was prepared for each group to which the amounts of calcium and phosphorus shown in Table 1 were added. After breeding on these feeds until the age of 6 weeks, the calcium concentration in the plasma was measured. As a result, the average was 8.1 mg / dl in group A, 9.1 mg / dl in group B, 10.0 mg / dl in group C, 10.5 mg / dl in group D, and 10.7 mg / dl in group E. Was. Example 5 35 male Wistar rats, 15 days old or around 15 days, were divided into 5 groups (A, B, C) of 7 rats each.
, D, and E), and the test feed used had the same composition as that of Example 2, and 3800
ng of 25-hydroxyvitamin D, 46 ng of 1.25-dihydroxyvitamin D
And 380 ng of 25.26-dihydroxyvitamin D, and the test feed was used as a control feed. As a base, as in Comparative Example 1 , a feed was prepared for each group to which the amounts of calcium and phosphorus shown in Table 1 were added. After breeding on these feeds until the age of 6 weeks, the calcium concentration in the plasma was measured. As a result, group A averaged 8.2 mg / dl, group B averaged 8.9 mg / dl, group C averaged 10.2 mg / dl, group D averaged 10.4 mg / dl, and group E averaged 10.9 mg / dl Was. Examples 3 to 5 show that these vitamin D metabolites require a certain amount of calcium and phosphorus in order to exert a calcium absorption promoting effect. COMPARATIVE EXAMPLE 4 35 male Wistar rats, 15 days old and 15 days old, were grouped into 7 groups, each comprising 5 groups (A, B, C).
, D and E), and the test feed used had the same composition as in Example 2. In this comparative example, as in Comparative Example 1 ,
For each group, a feed to which the calcium and phosphorus contents shown in Table 1 were added was prepared. After breeding in these captives up to the age of 6 weeks, the calcium concentration in plasma was measured. As a result, the average was 7.9 mg / dl in group A, 7.9 mg / dl in group B, 8.1 mg / dl in group C, 8.0 mg / dl in group D, and 8.2 mg / dl in group E. Was. According to the present invention, the vitamin D metabolite combination promotes the absorption of calcium, and a certain amount of calcium and phosphorus is required for the vitamin D metabolite to exhibit the calcium absorption promoting effect. It was found that vitamin D metabolite was added to infant formula containing calcium and phosphorus, so that the formula could exhibit a calcium absorption promoting effect more comparable to that of mother's milk.
Claims (1)
て、ビタミンＤ代謝産物として、２３・２５−ジハイドロキシビタミンＤ、２４
・２５−ジハイドロキシビタミンＤ及び２５・２６−ジハイドロキシビタミンＤ
の中から選択された一種以上を配合して成る育児用調製乳。 【請求項２】 請求項１記載の育児用調製乳に、さらに、２５ハイドロキシビ
タミンＤ及び／又は１・２５−ジハイドロキシビタミンＤを配合して成る育児用
調製乳。Claims: 1. A formula containing 23.25-dihydroxyvitamin D, 24 as a vitamin D metabolite for a baby formula containing calcium and phosphorus in the composition.
.25-dihydroxyvitamin D and 25.26-dihydroxyvitamin D
A formula for childcare comprising one or more selected from the group consisting of: 2. The infant formula according to claim 1, further comprising:
An infant formula prepared by mixing Tamine D and / or 1.25-dihydroxyvitamin D.
Family
ID=
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