JP2003511097A - Nutritional supplement - Google Patents
Nutritional supplementInfo
- Publication number
- JP2003511097A JP2003511097A JP2001530969A JP2001530969A JP2003511097A JP 2003511097 A JP2003511097 A JP 2003511097A JP 2001530969 A JP2001530969 A JP 2001530969A JP 2001530969 A JP2001530969 A JP 2001530969A JP 2003511097 A JP2003511097 A JP 2003511097A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- folic acid
- ester
- salt
- enhancing
- 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.)
- Withdrawn
Links
- 235000015872 dietary supplement Nutrition 0.000 title claims abstract description 9
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims abstract description 75
- 235000019152 folic acid Nutrition 0.000 claims abstract description 53
- 239000011724 folic acid Substances 0.000 claims abstract description 49
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims abstract description 26
- 229960000304 folic acid Drugs 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000000203 mixture Substances 0.000 claims abstract description 19
- 150000002148 esters Chemical class 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 230000006851 antioxidant defense Effects 0.000 claims abstract description 11
- 230000002708 enhancing effect Effects 0.000 claims abstract description 10
- 235000013305 food Nutrition 0.000 claims abstract description 10
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- 230000037406 food intake Effects 0.000 claims abstract description 6
- 230000007246 mechanism Effects 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 230000000694 effects Effects 0.000 claims description 23
- 239000000126 substance Substances 0.000 claims description 11
- 239000000654 additive Substances 0.000 claims description 4
- 239000012752 auxiliary agent Substances 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 2
- 235000012180 bread and bread product Nutrition 0.000 claims description 2
- 230000037396 body weight Effects 0.000 claims 1
- 229940014144 folate Drugs 0.000 description 23
- 108010008184 Aryldialkylphosphatase Proteins 0.000 description 19
- 102000006996 Aryldialkylphosphatase Human genes 0.000 description 19
- 210000002966 serum Anatomy 0.000 description 16
- 210000003743 erythrocyte Anatomy 0.000 description 8
- 108010010234 HDL Lipoproteins Proteins 0.000 description 7
- 102000015779 HDL Lipoproteins Human genes 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 230000003078 antioxidant effect Effects 0.000 description 5
- 208000029078 coronary artery disease Diseases 0.000 description 5
- 150000002224 folic acids Chemical class 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 235000013339 cereals Nutrition 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 208000037998 chronic venous disease Diseases 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 2
- MPJKWIXIYCLVCU-UHFFFAOYSA-N Folinic acid Natural products NC1=NC2=C(N(C=O)C(CNc3ccc(cc3)C(=O)NC(CCC(=O)O)CC(=O)O)CN2)C(=O)N1 MPJKWIXIYCLVCU-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- -1 alkali metal salts Chemical class 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 235000008429 bread Nutrition 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 235000008191 folinic acid Nutrition 0.000 description 2
- 239000011672 folinic acid Substances 0.000 description 2
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 229960001691 leucovorin Drugs 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- WYMSBXTXOHUIGT-UHFFFAOYSA-N paraoxon Chemical compound CCOP(=O)(OCC)OC1=CC=C([N+]([O-])=O)C=C1 WYMSBXTXOHUIGT-UHFFFAOYSA-N 0.000 description 2
- 229960004623 paraoxon Drugs 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 102220240796 rs553605556 Human genes 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 230000000778 atheroprotective effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000013622 meat product Nutrition 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000021067 refined food Nutrition 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
(57)【要約】 ヒトなどの主体の抗酸化防御機構を増強するための経口摂取用組成物、例えば食品、飼料または食品補助剤、の製造方法に関する。この方法においては、葉酸、それの塩またはエステルあるいはこれらの均等物質を有効成分として組成物に添加する。 (57) [Summary] The present invention relates to a method for producing a composition for oral ingestion, for example, a food, feed or food supplement, for enhancing the antioxidant defense mechanism of a human or the like. In this method, folic acid, a salt or ester thereof or an equivalent thereof is added to the composition as an active ingredient.
Description
【０００１】
本発明は、葉酸（folic acid）、それの塩またはエステル〔両者を集合的に“
ホレート（folate）”という〕、あるいはこれらと同等の生化学活性を有する均
等物質（例えばホリニン酸（folinic acid））を栄養補助剤または栄養強化剤と
して、食品や飼料などの内服用または経口摂取用組成物に用いる新規な方法に関
する。The present invention relates to folic acid, its salts or esters [collectively both
"Folate"] or an equivalent substance having biochemical activity equivalent to these (for example, folinic acid) as a nutritional supplement or fortifier for oral or oral intake of food or feed. It relates to a novel method for use in a composition.
【０００２】
血清中のホレート（葉酸の塩またはエステル）の低濃度は、心血管性疾患（ca
rdiovascular diseases, ＣＶＤ）の新しい危険因子として確立されているが、
ホレートがどのような機構によってＣＶＤの危険性を低下させるのかは不明であ
る。ホレートは、メチオニンを生じるホモシステイン（ｔＨｃｙ）の再メチル化
反応において重要な基質であり、葉酸は血漿ｔＨｃｙ濃度を低下させることで、
ＣＶＤの危険性を減少させると考えられる（文献１）。Low concentrations of folate (a salt or ester of folic acid) in serum cause cardiovascular disease (ca).
It has been established as a new risk factor for rdiovascular diseases (CVD),
It is unclear by what mechanism folates reduce the risk of CVD. Folate is an important substrate in the remethylation reaction of homocysteine (tHcy) that produces methionine, and folic acid reduces plasma tHcy concentration,
It is thought to reduce the risk of CVD (Reference 1).
【０００３】
ヒトの血清パラオキソナーゼ（paraoxonase, ＰＯＮ）は、高密度リポ蛋白（
ＨＤＬ）中の抗酸化酵素であり、血中の脂溶性ラジカルを除去し、冠状動脈疾患
を予防する（文献２〜４）。ＨＤＬコレステロールレベルの高い人は、冠状動脈
心臓疾患（ＣＨＤ）を発症する危険性が低いことを示す疫学的証拠がある。ＨＤ
Ｌが抗酸化作用を示すことは証明されており、この抗酸化作用はＨＤＬによるＣ
ＨＤの防御に寄与していると考えられる。パラオキソナーゼ／アリルエステラー
ゼは、ＨＤＬの抗酸化作用において重要な部分を占めていると考えられる（文献
５）。また、心筋梗塞（ＭＩ）患者のＰＯＮ活性は低下しているという報告もあ
る（文献２〜３）。Human serum paraoxonase (PON) is a high-density lipoprotein (
It is an antioxidant enzyme in HDL), removes fat-soluble radicals in blood, and prevents coronary artery disease (References 2 to 4). There is epidemiological evidence that people with high HDL cholesterol levels have a lower risk of developing coronary heart disease (CHD). HD
It has been proved that L has an antioxidant effect, and this antioxidant effect is due to C by HDL.
It is considered to contribute to the protection of HD. Paraoxonase / allyl esterase is considered to play an important part in the antioxidant action of HDL (Reference 5). There are also reports that PON activity in patients with myocardial infarction (MI) is reduced (References 2 to 3).
【０００４】
本発明は、血中ホレート濃度またはホレートの経口摂取量と、血清ＰＯＮ活性
の増加との間に正の相関があるという知見にもとづくものである。血清ＰＯＮ活
性の増加は、主体（subject）（例えば人）の内因性の抗酸化能および防御能を
増強し、その結果、様々な疾患、例えばＣＨＤ、癌、ＩＩ型糖尿病および白内障
、の危険性を減少させる。また、血清ＰＯＮ活性は加齢の過程にも関与している
。The present invention is based on the finding that there is a positive correlation between blood folate concentration or oral intake of folate and an increase in serum PON activity. Increasing serum PON activity enhances the subject's (eg, human's) intrinsic antioxidant and protective capacities, resulting in the risk of various diseases such as CHD, cancer, type II diabetes and cataracts. To reduce. Serum PON activity is also involved in the aging process.
【０００５】
最も広義において、本発明は、葉酸あるいはそれの塩またはエステルを補助剤
として用いて、生体の内因性の抗酸化防御能を増強する方法に関する。本発明に
おいては、前記したように「ホレート（folate）」とは、 葉酸の塩またはエス
テルを意味する。ホレートとして許容できる葉酸塩には、ナトリウム塩等のアル
カリ金属塩およびメチルグルカミン塩が含まれる。葉酸のエステルは、当業者に
は良く知られている公知の方法で調製することができる。In its broadest sense, the present invention relates to a method of enhancing the endogenous antioxidant defense ability of a living body by using folic acid or a salt or ester thereof as an auxiliary agent. In the present invention, as described above, the “folate” means a salt or ester of folic acid. Folates acceptable as folates include alkali metal salts such as sodium salts and methylglucamine salts. Folic acid esters can be prepared by known methods well known to those skilled in the art.
【０００６】
従って、本発明の主たる目的は、抗酸化防御能の増強効果を有する経口摂取用
組成物の製造方法であって、葉酸、それの塩またはエステルあるいはこれらの均
等物質を活性成分または有効成分として使用することを特徴とする方法を提供す
ることである。Therefore, a main object of the present invention is to provide a method for producing a composition for oral ingestion having an effect of enhancing antioxidant defense ability, which comprises using folic acid, a salt or ester thereof, or an equivalent substance thereof as an active ingredient or an effective ingredient. It is to provide a method characterized by being used as an ingredient.
【０００７】
本発明の第２の態様の目的は、抗酸化防御能の増強効果を有する経口摂取用組
成物を製造するために、葉酸、それの塩またはエステルあるいはこれらの均等物
質を補助剤または添加物として用いる方法を提供することである。The object of the second aspect of the present invention is to prepare folic acid, a salt or ester thereof, or an equivalent substance thereof as an adjuvant or to prepare a composition for oral ingestion having an effect of enhancing antioxidant defense ability. It is to provide a method for use as an additive.
【０００８】
本発明の第３の態様の目的は、主体の抗酸化防御能を増強するための方法であ
って、抗酸化防御能の増強に有効な量の葉酸、それの塩またはエステルあるいは
これらの均等物質を主体に（例えば経口的または非経口的に）投与することを特
徴とする方法を提供することである。An object of the third aspect of the present invention is a method for enhancing the antioxidant defense ability of a subject, which comprises an effective amount of folic acid, a salt or ester thereof, or an effective amount for enhancing the antioxidant defense ability. It is intended to provide a method comprising administering a substance equivalent to the above as a main ingredient (for example, orally or parenterally).
【０００９】
葉酸あるいはこれの塩またはエステルの均等物質とは、葉酸と同じ生化学活性
を有する物質を意味し、具体的にはホリニン酸やそれの塩またはエステルが挙げ
られる。The equivalent substance of folic acid or its salt or ester means a substance having the same biochemical activity as folic acid, and specific examples thereof include folinic acid and its salts or esters.
【００１０】
本発明において「主体（subject）」とは、哺乳類（ヒトなど）あるいは動物
、とりわけ家畜または牧畜を意味する。In the present invention, the term “subject” means mammals (such as humans) or animals, especially livestock or livestock.
【００１１】
本発明において「有効な量」とは、有効成分を主体に投与した際に、主体の血
清パラオキソナーゼ活性を高め、それに伴って抗酸化防御能を増強するのに充分
な有効成分の量を意味する。以下の記載においては、葉酸とホレートを互いに置
換えることができる。In the present invention, an “effective amount” is an active ingredient sufficient to enhance the serum paraoxonase activity of the subject when the active ingredient is administered to the subject, and to enhance the antioxidant defense ability accordingly. Means the amount of. In the following description, folic acid and folate can be substituted for each other.
【００１２】
本発明の組成物は、経口摂取可能な（典型的には経口投与用の）組成物、製剤
または製品である限り特に限定はなく、食品、飼料、食品補助剤、医薬製剤また
はこれらの原料などである。The composition of the present invention is not particularly limited as long as it is a composition, preparation or product that can be orally ingested (typically for oral administration), and it may be a food, feed, food supplement, pharmaceutical preparation, or these. Are raw materials of.
【００１３】
葉酸、それの塩またはエステル、あるいはこれらと同等の生化学活性を有する
均等物質を栄養補助剤または栄養強化剤として添加する組成物は、原則としてい
かなる食品や飼料であってもよい。本発明の態様の具体例によると、葉酸または
それの均等物質である誘導体を穀物に添加して栄養を補助した穀物を得、それを
穀物を主原料とする食品または飼料に使用するか、あるいは、パン製品、シリア
ル、スナックフード、飲料等の食品や飼料に葉酸またはそれの誘導体を補助剤と
して添加することが考えられる。また、葉酸またはそれの誘導体は、添加物を安
定に含有し、主体に分配することが可能ないかなる種類の食品や飼料、例えばソ
ーセージのような肉製品やその他の加工食品、に加えることもできる。さらに、
本発明の栄養補助剤を牛乳、チーズ、バターおよびヨーグルトなどの乳製品や、
果汁飲料およびジュースなどの飲料に加えてその栄養価を強化することもできる
。The composition to which folic acid, a salt or ester thereof, or an equivalent substance having a biochemical activity equivalent to these is added as a nutritional supplement or fortifier may be any food or feed in principle. According to an embodiment of the invention, folic acid or its equivalent derivative is added to the grain to obtain a nutritionally supplemented grain, which is used in foods or feeds based on the grain, or It is possible to add folic acid or its derivative as an auxiliary agent to foods and feeds such as bread products, cereals, snack foods and beverages. Folic acid or a derivative thereof can also be added to any kind of food or feed that stably contains additives and can be distributed to the main body, such as meat products such as sausage and other processed foods. . further,
Milk supplements of the present invention milk, cheese, dairy products such as butter and yogurt,
In addition to beverages such as fruit juices and juices, their nutritional value can be enhanced.
【００１４】
栄養補助剤は、経口投与のための錠剤、カプセル、ロゼンジ（舐剤）、顆粒、
シロップ、溶液または分散液として提供することが可能であり、葉酸又はホレー
トを担体または充填剤、例えばラクトース、シリカ、グルコース、スターチ、グ
リセロール、希釈剤および溶剤、と共に含有させることが好ましい。このような
剤形は、公知の添加剤、例えば、流動促進剤、安定化剤、着色剤、保存料、味質
改良剤などを含んでいても良く、コロイド状の無水シリカを含むメチルセルロー
スまたは微結晶セルロースのような、薬剤の吸収を遅らせるための基質を含んで
いてもよい。上記のような剤形の補助剤の調製方法は、当業者には公知の技術で
ある。Dietary supplements include tablets, capsules, lozenges, granules for oral administration,
It can be provided as a syrup, solution or dispersion, preferably containing folic acid or folates, together with carriers or fillers such as lactose, silica, glucose, starch, glycerol, diluents and solvents. Such dosage forms may contain known additives such as glidants, stabilizers, colorants, preservatives, taste improvers and the like, such as methylcellulose containing colloidal anhydrous silica or finely divided. It may also include a matrix such as microcrystalline cellulose to delay absorption of the drug. The method for preparing an auxiliary agent in the above dosage form is a technique known to those skilled in the art.
【００１５】
経口摂取用組成物に含まれる葉酸またはそれの均等物質の含有量は、栄養を補
助または強化する製品の種類のみならず、摂取頻度および摂取濃度によって大き
く変化する。当業者はこれらの値を公知技術に基いて容易に決定し、そこから適
切な栄養補助剤の１日当りの摂取量を求め、主体に与えることができる。典型的
な摂取量は、例えば、普通の大きさの主体、即ち体重約８０ｋｇのヒトの場合、
１日に１５〜１２００μｇのホレート、あるいは１日に体重１ｋｇあたり約０．
２〜１５μｇのホレートである。この量のホレートを、例えばパン、具体的には
適切な１食分である１００ｇのパン、に添加することができる。The content of folic acid or its equivalent substance contained in the composition for oral ingestion largely varies depending on not only the type of product that supplements or enhances nutrition, but also the intake frequency and intake concentration. Those skilled in the art can easily determine these values based on known techniques, determine the daily intake of an appropriate nutritional supplement from the values, and provide them to the subject. A typical intake is, for example, for a person of normal size, ie a human weighing about 80 kg,
15 to 1200 μg of folate per day, or about 0.
2 to 15 μg of folate. This amount of folate can be added to, for example, bread, specifically 100 g of bread, which is a suitable serving.
【００１６】実施例
血清ＰＯＮ酵素活性はパラオキソンの加水分解に基づいて分析し、赤血球ホレ
ート濃度はＲＩＡで測定した。初めに、赤血球ホレートと血清ＰＯＮ活性の関係
を、人口に基いて抽出した５３歳〜７１歳の男性１５５人について調査した。こ
の調査は、１９９８年から１９９９年にかけてクオピオ虚血性心疾患危険因子調
査（Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD)）の一環とし
て行われたものである。血清ＰＯＮ活性と赤血球ホレート濃度との相関係数は０
．２５（Ｐ＝０．００２）であった。血清ＰＯＮ活性の未修正の平均値（９５％
信頼区間（ＣＩ））は、全標本の５分の一に相当する赤血球ホレート濃度が最も
低い集団（６３．２、４７．５〜７９．０ｎｍｏｌ／ｍＬ／ｍｉｎ）の方が、全
標本の５分の一に相当する赤血球ホレート濃度が最も高い集団の値（８５．７、
６３．２〜１０８．２ｎｍｏｌ／ｍＬ／ｍｉｎ ）よりも２６．３％も低かった
。 EXAMPLE Serum PON enzyme activity was analyzed based on the hydrolysis of paraoxon and red blood cell folate concentrations were measured by RIA. First, the relationship between erythrocyte folate and serum PON activity was investigated in 155 males aged 53 to 71 years, which were extracted based on population. This survey was conducted as part of the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) from 1998 to 1999. The correlation coefficient between serum PON activity and red blood cell folate concentration is 0.
． It was 25 (P = 0.002). Uncorrected mean serum PON activity (95%
The confidence interval (CI) is 5 for all samples in the population (63.2, 47.5-79.0 nmol / mL / min) with the lowest red blood cell folate concentration corresponding to one fifth of all samples. The value of the population with the highest erythrocyte folate concentration (85.7,
26.3% lower than 63.2-108.2 nmol / mL / min).
【００１７】
上記の調査結果を実験的に証明するために、プラシーボを用いた二重盲式試験
によって、ホレートの経口投与がＰＯＮ活性に与える影響について検討した。こ
の試験では、１９歳〜３６歳の健常なボランティア男性３９人に無作為に０．９
ｍｇのホレートまたはプラシーボを８週にわたって投与した。試験期間中の赤血
球ホレート濃度の変化とＰＯＮ活性との相関係数は０．３６（Ｐ＝０．０２５）
であった。平均血清ＰＯＮ活性は、葉酸摂取群において４．０％（２．４３ｎｍ
ｏｌ／ｍＬ／ｍｉｎ）増加し、プラシーボ摂取群においては３．６％（−２．８
７ｎｍｏｌ／ｍＬ／ｍｉｎ）減少した（２群間の差に関しては、Ｐ＝０．０１５
）。赤血球ホレート濃度の変化と血漿中の全ホモシステイン（ｔＨｃｙ）濃度の
変化との相関係数は、−０．６２（Ｐ＜０．００１）であり、血漿ホモシステイ
ン（ｔＨｃｙ）濃度の変化と血清ＰＯＮ酵素活性との相関係数は、−０．２５（
Ｐ＝０．１３４）であった。直線型回帰モデルによれば、血清ＰＯＮ活性の変化
の最も強力な予測変数は、赤血球ホレート濃度の変化（標準化係数は０．４１、
Ｐ＝０．０１０）および年齢（０．２７、Ｐ＝０．０９１）であった（モデルに
対する補正Ｒ二乗値は０．１５１、Ｐ＝０．０２０）。In order to experimentally prove the above-mentioned investigation results, the effect of oral administration of folate on PON activity was examined by a double blind test using a placebo. In this study, 39 healthy male volunteers aged 19 to 36 were randomly assigned 0.9
mg folate or placebo was administered over 8 weeks. Correlation coefficient between PON activity and change in red blood cell folate concentration during the test period is 0.36 (P = 0.025)
Met. The average serum PON activity was 4.0% (2.43 nm) in the folic acid intake group.
ol / mL / min), and 3.6% (−2.8%) in the placebo ingestion group.
7 nmol / mL / min) (P = 0.015 for the difference between the two groups)
). The correlation coefficient between the change in red blood cell folate concentration and the change in plasma total homocysteine (tHcy) concentration is -0.62 (P <0.001), and the change in plasma homocysteine (tHcy) concentration and serum The correlation coefficient with the PON enzyme activity is -0.25 (
P = 0.134). According to the linear regression model, the strongest predictor of change in serum PON activity was change in red blood cell folate concentration (standardization coefficient 0.41,
P = 0.010) and age (0.27, P = 0.091) (corrected R-squared value for the model was 0.151, P = 0.020).
【００１８】
従って、試験結果によって、ホレートの投与と血中ホレート濃度がヒトの血清
ＰＯＮ活性に影響をおよぼすことが示された。Therefore, the test results showed that the administration of folate and the blood folate concentration had an influence on the serum PON activity in humans.
【００１９】
参考文献
1. Verhoef P, Stampfer MJ, Rimm EB. Folate and coronary heart disease.
Curr. Opin. Lipid. 9, 17-22 (1998).
2. McElveen J, et al. Distribution of paraoxon hydralytic activity in
the serum of patients after myocardial infarction. Clin. Chem. 32, 671-
3 (1986).
3. Ayub A, et al. Serum paraoxonase after myocardial infraction. Arte rioscler
. Thromb. Vasc. Biol. 19, 331-5 (1999).
4. Salonen JT, et al. Polymorphism in high density lipoprotein paraoxo
nase gene and risk of acute myocardial infraction in men: prospective ne
sted case-control study. Brit. Med. J. 319, 487-488 (1999).
5. Stein O, Stein Y. Atheroprotective mechanisms of HDL. Atherosclero sis
144, 285-301 (1999). References 1. Verhoef P, Stampfer MJ, Rimm EB. Folate and coronary heart disease.
Curr . Opin . Lipid . 9, 17-22 (1998). 2. McElveen J, et al. Distribution of paraoxon hydralytic activity in
the serum of patients after myocardial infarction. Clin . Chem . 32, 671-
3 (1986). 3. Ayub A , et al. Serum paraoxonase after myocardial infraction. Arte rioscler. Thromb. Vasc. Biol. 19, 331-5 (1999). 4. Salonen JT, et al. Polymorphism in high density lipoprotein paraoxo
nase gene and risk of acute myocardial infraction in men: prospective ne
sted case-control study. Brit. Med. J. 319, 487-488 (1999). 5. Stein O, Stein Y. Atheroprotective mechanisms of HDL. Atherosclero sis 144, 285-301 (1999).
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ａ６１Ｐ 9/00 Ａ６１Ｐ 9/00 (81)指定国 ＥＰ(ＡＴ，ＢＥ，ＣＨ，ＣＹ， ＤＥ，ＤＫ，ＥＳ，ＦＩ，ＦＲ，ＧＢ，ＧＲ，ＩＥ，Ｉ Ｔ，ＬＵ，ＭＣ，ＮＬ，ＰＴ，ＳＥ)，ＯＡ(ＢＦ，ＢＪ ，ＣＦ，ＣＧ，ＣＩ，ＣＭ，ＧＡ，ＧＮ，ＧＷ，ＭＬ， ＭＲ，ＮＥ，ＳＮ，ＴＤ，ＴＧ)，ＡＰ(ＧＨ，ＧＭ，Ｋ Ｅ，ＬＳ，ＭＷ，ＭＺ，ＳＤ，ＳＬ，ＳＺ，ＴＺ，ＵＧ ，ＺＷ)，ＥＡ(ＡＭ，ＡＺ，ＢＹ，ＫＧ，ＫＺ，ＭＤ， ＲＵ，ＴＪ，ＴＭ)，ＡＥ，ＡＧ，ＡＬ，ＡＭ，ＡＴ， ＡＵ，ＡＺ，ＢＡ，ＢＢ，ＢＧ，ＢＲ，ＢＹ，ＢＺ，Ｃ Ａ，ＣＨ，ＣＮ，ＣＲ，ＣＵ，ＣＺ，ＤＥ，ＤＫ，ＤＭ ，ＤＺ，ＥＥ，ＥＳ，ＦＩ，ＧＢ，ＧＤ，ＧＥ，ＧＨ， ＧＭ，ＨＲ，ＨＵ，ＩＤ，ＩＬ，ＩＮ，ＩＳ，ＪＰ，Ｋ Ｅ，ＫＧ，ＫＰ，ＫＲ，ＫＺ，ＬＣ，ＬＫ，ＬＲ，ＬＳ ，ＬＴ，ＬＵ，ＬＶ，ＭＡ，ＭＤ，ＭＧ，ＭＫ，ＭＮ， ＭＷ，ＭＸ，ＭＺ，ＮＯ，ＮＺ，ＰＬ，ＰＴ，ＲＯ，Ｒ Ｕ，ＳＤ，ＳＥ，ＳＧ，ＳＩ，ＳＫ，ＳＬ，ＴＪ，ＴＭ ，ＴＲ，ＴＴ，ＴＺ，ＵＡ，ＵＧ，ＵＳ，ＵＺ，ＶＮ， ＹＵ，ＺＡ，ＺＷ Ｆターム(参考） 2B150 AA01 DE09 4B018 MB01 MD07 ME06 4B032 DK05 DL20 4C086 AA02 CB09 MA01 MA04 MA52 ZA36 ─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. 7 Identification code FI theme code (reference) A61P 9/00 A61P 9/00 (81) Designated country EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, MZ, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD) , RU, TJ, TM), AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN, CR, CU, C , DE, DK, DM, DZ, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI , SK, SL, TJ, TM, TR, TT, TZ, UA, UG, US, UZ, VN, YU, ZA, ZW F terms (reference) 2B150 AA01 DE09 4B018 MB01 MD07 ME06 4B032 DK05 DL20 4C086 AA02 CB09 MA01 MA04 MA52 ZA36
Claims (8)
法であって、葉酸、それの塩またはエステルあるいはこれらの均等物質を該組成
物の有効成分として使用することを特徴とする、組成物の製造方法。1. A method for producing an orally ingested composition having an antioxidant defense enhancing effect, which comprises using folic acid, a salt or ester thereof, or an equivalent thereof as an active ingredient of the composition. A method for producing a composition, which is characterized.
らの原料であることを特徴とする、請求項１に記載の方法。2. The method according to claim 1, wherein the composition is a food, a feed, a food supplement, a pharmaceutical preparation or a raw material thereof.
たはエステルの量が、該組成物を摂取する主体が１日にその体重１ｋｇあたり０
．２〜１５μｇの葉酸あるいはそれの塩またはエステルを経口摂取できる量であ
ることを特徴とする、請求項１または２に記載の方法。3. The amount of folic acid or a salt or ester thereof used as an active ingredient of the composition is 0 per 1 kg of body weight of the subject who ingests the composition per day.
． The method according to claim 1 or 2, wherein the amount is 2 to 15 µg of folic acid or a salt or ester thereof, which can be taken orally.
はそれの塩またはエステルを摂取できる量の有効成分を含有する組成物、例えば
パン製品、であることを特徴とする、請求項１または２に記載の方法。4. The composition is characterized in that the main component is a composition, for example, a bread product, containing 15 to 1200 μg of folic acid or a salt or ester thereof in an amount such that the active ingredient can be taken daily. The method according to claim 1 or 2.
るために、葉酸、それの塩またはエステルあるいはこれらの均等物質を補助剤ま
たは添加物として用いる方法。5. A method of using folic acid, a salt or ester thereof, or an equivalent substance thereof as an auxiliary agent or an additive in order to produce a composition for oral ingestion having an effect of enhancing antioxidant defense ability.
らの原料であることを特徴とする、請求項５に記載の方法。6. The method according to claim 5, wherein the composition is a food, a feed, a food supplement, a pharmaceutical preparation or a raw material thereof.
化防御機構の増強に有効な量の葉酸、それの塩またはエステルあるいはこれらの
均等物質を主体に投与することを特徴とする方法。7. A method for enhancing the antioxidant defense mechanism of a subject, comprising administering to the subject a folic acid, a salt or ester thereof, or an equivalent substance thereof in an amount effective for enhancing the antioxidant defense mechanism. A method characterized by.
塩またはエステルあるいはこれらの均等物質を投与することを特徴とする、請求
項７に記載の方法。8. The method according to claim 7, wherein the subject is administered with 0.2 to 15 μg / kg of folic acid, a salt or ester thereof, or an equivalent substance thereof per day.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI992239A FI19992239A (en) | 1999-10-18 | 1999-10-18 | nutritional Supplement |
| FI19992239 | 1999-10-18 | ||
| PCT/FI2000/000899 WO2001028365A1 (en) | 1999-10-18 | 2000-10-17 | Dietary supplement |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2003511097A true JP2003511097A (en) | 2003-03-25 |
Family
ID=8555463
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001530969A Withdrawn JP2003511097A (en) | 1999-10-18 | 2000-10-17 | Nutritional supplement |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1221868A1 (en) |
| JP (1) | JP2003511097A (en) |
| AU (1) | AU7927200A (en) |
| FI (1) | FI19992239A (en) |
| WO (1) | WO2001028365A1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6420342B1 (en) | 2000-05-08 | 2002-07-16 | N.V. Nutricia | Nutritional preparation comprising ribose and medical use thereof |
| US6740746B2 (en) | 2001-03-20 | 2004-05-25 | Oy Jurilab Ltd. | DNA molecule encoding a variant paraoxonase and uses thereof |
| DE10301354A1 (en) | 2003-01-16 | 2004-07-29 | Esa Patentverwertungsagentur Sachsen-Anhalt Gmbh | To produce raw sausages, with an accelerated ripening, folic acid and/or folates are added with the herbs/spices for an even distribution to provide micrococcus and/or lactobacillus |
| ES2302571B2 (en) * | 2005-03-18 | 2009-03-16 | Universidad Complutense De Madrid | PROCEDURE FOR OBTAINING COOKED ENRICHED ENERGIES WITH FOLIC ACID. |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA936723B (en) * | 1992-09-14 | 1995-08-14 | Vesta Med Pty Ltd | Pharmaceutical preparations for lowering homocysteine levels |
| US5932624A (en) * | 1995-10-17 | 1999-08-03 | Herbert; Victor D. | Vitamin supplement composition |
| DE29808384U1 (en) * | 1998-05-08 | 1998-08-06 | Eckes Granini Gmbh Co Kg | drink |
| US6121249A (en) * | 1998-07-01 | 2000-09-19 | Donald L. Weissman | Treatment and prevention of cardiovascular diseases with help of aspirin, antioxidants, niacin, and certain B vitamins |
-
1999
- 1999-10-18 FI FI992239A patent/FI19992239A/en unknown
-
2000
- 2000-10-17 AU AU79272/00A patent/AU7927200A/en not_active Abandoned
- 2000-10-17 EP EP00969600A patent/EP1221868A1/en not_active Withdrawn
- 2000-10-17 WO PCT/FI2000/000899 patent/WO2001028365A1/en not_active Application Discontinuation
- 2000-10-17 JP JP2001530969A patent/JP2003511097A/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO2001028365A1 (en) | 2001-04-26 |
| EP1221868A1 (en) | 2002-07-17 |
| FI19992239A (en) | 2001-04-19 |
| AU7927200A (en) | 2001-04-30 |
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