JP2005225874A - Iron supplement and utilization of the same - Google Patents
Iron supplement and utilization of the same Download PDFInfo
- Publication number
- JP2005225874A JP2005225874A JP2005006829A JP2005006829A JP2005225874A JP 2005225874 A JP2005225874 A JP 2005225874A JP 2005006829 A JP2005006829 A JP 2005006829A JP 2005006829 A JP2005006829 A JP 2005006829A JP 2005225874 A JP2005225874 A JP 2005225874A
- Authority
- JP
- Japan
- Prior art keywords
- iron
- siderophore
- food composition
- trivalent
- ferriclysin
- 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.)
- Granted
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- 239000011975 tartaric acid Substances 0.000 description 1
- JHYAVWJELFKHLM-UHFFFAOYSA-H tetrasodium;2-hydroxypropane-1,2,3-tricarboxylate;iron(2+) Chemical compound [Na+].[Na+].[Na+].[Na+].[Fe+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O JHYAVWJELFKHLM-UHFFFAOYSA-H 0.000 description 1
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- LLMKLMMXMOTPRU-YOAXHERRSA-N vibriobactin Chemical compound O=C([C@@H]1N=C(O[C@H]1C)C=1C(=C(O)C=CC=1)O)NCCCN(C(=O)[C@@H]1[C@H](OC(=N1)C=1C(=C(O)C=CC=1)O)C)CCCNC(=O)C1=CC=CC(O)=C1O LLMKLMMXMOTPRU-YOAXHERRSA-N 0.000 description 1
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- 229940100445 wheat starch Drugs 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
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- Coloring Foods And Improving Nutritive Qualities (AREA)
- Non-Alcoholic Beverages (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
本発明は、シデロフォアを利用した鉄補給剤、鉄欠乏性貧血の予防又は治療剤、食品添加剤、及び食品組成物に関する。 The present invention relates to an iron supplement using siderophore, an agent for preventing or treating iron deficiency anemia, a food additive, and a food composition.
近年、日本人の食生活及び健康に対する意識は高くなり、食品に安全性及び機能性が求められるようになってきた。通常の食事で不足する成分を補うため栄養補助食品などを摂取する人の割合もますます増えてきている。一方、国民栄養調査によると、鉄の平均摂取量は性別や年代に関係なく、所要量を下回る状態が続いている。また、鉄は吸収率が低く、摂取した量のほとんどが排泄されてしまうことが知られている。このことから、鉄は積極的に摂取する必要がある栄養素のひとつである。
鉄が不足した状態が長く続くと鉄欠乏性貧血になるばかりでなく、運動及び学習能力が低下したり、免疫力が低下したりするなど、人体に様々な悪影響を及ぼす。鉄欠乏性貧血を改善するには、一般に、ヒトが吸収し易いヘム鉄を多く含む畜肉又は魚類を摂取することが有効といわれている。しかし、畜肉又は魚類を多量に摂取するには食習慣を大きく変える必要があり、またこれらを過剰に摂取すると栄養のバランスが悪くなる。一方、野菜などの植物に含まれる鉄は非ヘム鉄であり、非ヘム鉄の吸収率はヘム鉄の吸収率の1/2から1/5程度である。さらに非ヘム鉄は食物繊維や緑茶に含まれるカテキン等によって吸収が阻害され易い。従って、植物から充分量の鉄を摂ることは現実的でない。
In recent years, Japanese people's consciousness about eating habits and health has increased, and foods have been required to have safety and functionality. An increasing proportion of people take dietary supplements to make up for the deficiencies in a normal diet. On the other hand, according to the National Nutrition Survey, the average iron intake remains below the required level regardless of gender and age. Moreover, it is known that iron has a low absorption rate and most of the ingested amount is excreted. For this reason, iron is one of the nutrients that need to be actively consumed.
If iron deficiency continues for a long time, not only iron deficiency anemia will occur, but also the ability to exercise and learn and immunity will decline, causing various adverse effects on the human body. In order to improve iron deficiency anemia, it is generally said that it is effective to ingest livestock meat or fish containing a lot of heme iron that is easily absorbed by humans. However, ingesting large amounts of livestock meat or fish requires a significant change in eating habits, and excessive intake of these results in poor nutritional balance. On the other hand, iron contained in plants such as vegetables is non-heme iron, and the absorption rate of non-heme iron is about 1/2 to 1/5 of the absorption rate of heme iron. Furthermore, absorption of non-heme iron is likely to be inhibited by dietary fiber or catechin contained in green tea. Therefore, taking a sufficient amount of iron from plants is not practical.
従来、鉄の補給により貧血を予防又は治療するために、ピロリン酸鉄、クエン酸鉄、硫酸鉄等の各種鉄剤が用いられている。しかし、これらの鉄剤に含まれる鉄は一般に生体内で利用率が低いため、貧血の予防又は治療効果を得るためには、多量を摂取する必要がある。しかし、これらの鉄塩は多量の摂取により胃腸粘膜障害又は嘔吐などを引き起こす恐れがあるため、短期間に多量を摂取することは難しい。従って、貧血予防又は治療効果を得るためには、これらの鉄塩を長期間に亘り摂取する必要がある。
従来使用されているその他の鉄補給剤としては、乳汁に含まれるラクトフェリンが挙げられる。ラクトフェリンは鉄結合能を持つ糖タンパクであることが知られている。特許文献1は、鉄−ラクトフェリン複合体の増血効果及びその製造方法を開示している。しかし、鉄−ラクトフェリン複合体は、溶解性が悪く、また鉄の所要量に対し多量のラクトフェリンを摂取する必要があることから、鉄剤としては実用化するには多くの課題が残されている。
また非特許文献1は、EDTA−FeNaを有効成分とする鉄強化剤の吸収の検討結果を開示している。しかし、EDTAは生体内の多くの微量金属に対し強いキレート化作用を有するため、生体内の必要金属をキレート化により不活性化する可能性があることから、EDTA−FeNaを有効成分とする鉄強化剤の長期継続摂取は健康面で懸念される。
一方、清酒の醸造においては、カビの一種である麹菌(アスペルギルス・オリゼ;Aspergillus oryzae)を蒸米上に生育させて「麹」を作製し、清酒醸造の副原料として利用している。この麹造りにおいて、麹菌が大量のフェリクローム類、主にデフェリフェリクリシンを生産し、このフェリクローム類が酒造用水由来の鉄イオンをキレート化することにより清酒が着色することが古くから知られている。このように、麹菌は多量のフェリクローム類を生産することが知られているが、清酒醸造においてはフェリクローム類は清酒の品質劣化の原因であることから、その有効利用は全く考えられていない。
Other iron supplements conventionally used include lactoferrin contained in milk. Lactoferrin is known to be a glycoprotein with iron binding ability. Patent Document 1 discloses a blood-enhancing effect of an iron-lactoferrin complex and a production method thereof. However, since the iron-lactoferrin complex has poor solubility and needs to consume a large amount of lactoferrin with respect to the required amount of iron, many problems remain to be put into practical use as an iron agent.
Non-Patent Document 1 discloses the results of studies on absorption of iron reinforcing agents containing EDTA-FeNa as an active ingredient. However, since EDTA has a strong chelating action on many trace metals in the living body, it may inactivate necessary metals in the living body by chelation, so iron containing EDTA-FeNa as an active ingredient Long-term continuous use of fortifiers is a health concern.
On the other hand, in sake brewing, Aspergillus oryzae, which is a kind of mold, is grown on steamed rice to produce “mochi” and used as an auxiliary material for sake brewing. In this koji making, it has long been known that koji molds produce large amounts of ferrichromes, mainly deferriferricricin, and this ferrichromes chelate iron ions from brewing water to color sake. ing. As described above, koji molds are known to produce a large amount of ferrichromes. However, in sake brewing, ferrichromes are a cause of quality degradation of sake, and their effective use is not considered at all. .
本発明は、生体内への鉄の吸収率が高い鉄補給剤、鉄欠乏性貧血の予防又は治療剤、食品添加剤、及び食品組成物を提供することを課題とする。 An object of the present invention is to provide an iron supplement with a high absorption rate of iron into a living body, a prophylactic or therapeutic agent for iron deficiency anemia, a food additive, and a food composition.
上記課題を解決するために本発明者は研究を重ね、以下の知見を得た。
(1) 鉄欠乏による貧血は、肝臓の貯蔵鉄が欠乏する第1段階、血清中の鉄が欠乏する第2段階、及び、ヘモグロビン合成能が低下して貧血症状が現れる第3段階を経て進行する。また鉄欠乏性貧血はこの逆の段階を経て快復する。
In order to solve the above-mentioned problems, the present inventor repeated research and obtained the following knowledge.
(1) Anemia due to iron deficiency progresses through the first stage in which liver stored iron is deficient, the second stage in which iron in the serum is deficient, and the third stage in which the ability to synthesize hemoglobin decreases and anemia appears. To do. Iron deficiency anemia recovers through the reverse phase.
シデロフォアの3価鉄キレート錯体は、鉄欠乏性貧血ラットに摂取させた場合、生体内に効率的に吸収されて血清中の鉄濃度及び血中ヘモグロビン濃度を増加させ、さらに肝臓の貯蔵鉄も増加させる。従って、シデロフォアの3価鉄キレート錯体は、鉄欠乏による各種症状、特に鉄欠乏性貧血の予防、改善又は治療剤として有用である。
(2) シデロフォアの3価鉄キレート錯体は、ラットに摂取させた場合、体重増加量、摂食量、肝機能及び腎機能に悪影響を与えないため、安全な鉄補給剤である。
(3) シデロフォアの3価鉄キレート錯体は、水に対する溶解性が高く、鉄化合物が沈殿することがある酸性条件下でも高い水溶性を示すため、液状食品への添加剤として使用し易い。
(4) シデロフォアの3価鉄キレート錯体は、広いpH範囲の下での加熱加圧に対して極めて安定であり、変性しない。従って、医薬組成物又は食品組成物の成分として使用する場合に、これらの組成物を加熱加圧滅菌できる。
(5) シデロフォアの3価鉄キレート錯体を0.05〜10mg/ml含む液体状食品組成物は、無理のない摂取スケジュールで鉄欠乏性貧血を効果的に予防又は改善できるとともに、副作用が生じない。
(6) シデロフォアの3価鉄キレート錯体を0.1〜5mg/g含む固体状食品組成物は、無理のない摂取スケジュールで鉄欠乏性貧血を効果的に予防又は改善できるとともに、副作用が生じない。
The trivalent iron chelate complex of siderophore is efficiently absorbed into the body when ingested by iron-deficient anemia rats, increasing serum iron concentration and blood hemoglobin concentration, and also increasing liver stored iron Let Therefore, the trivalent iron chelate complex of siderophore is useful as an agent for preventing, improving or treating various symptoms caused by iron deficiency, particularly iron deficiency anemia.
(2) The trivalent iron chelate complex of siderophore is a safe iron supplement because it does not adversely affect body weight gain, food intake, liver function and kidney function when ingested by rats.
(3) The trivalent iron chelate complex of siderophore is highly soluble in water and exhibits high water solubility even under acidic conditions where iron compounds may precipitate, and is therefore easy to use as an additive to liquid foods.
(4) The trivalent iron chelate complex of siderophore is extremely stable to heating and pressurization under a wide pH range and does not denature. Therefore, when used as a component of a pharmaceutical composition or a food composition, these compositions can be heat sterilized.
(5) A liquid food composition containing 0.05 to 10 mg / ml of a trivalent iron chelate complex of siderophore can effectively prevent or improve iron deficiency anemia with a reasonable intake schedule and does not cause side effects .
(6) A solid food composition containing 0.1 to 5 mg / g of a siderophore trivalent iron chelate complex can effectively prevent or ameliorate iron deficiency anemia with a reasonable intake schedule and does not cause side effects. .
本発明は上記知見に基づき完成されたものであり、以下の鉄補給剤などを提供する。 The present invention has been completed based on the above findings, and provides the following iron supplements and the like.
項1. シデロフォアと3価鉄イオンとを含む鉄補給剤。 Item 1. An iron supplement containing siderophore and trivalent iron ions.
項2. シデロフォアと3価鉄イオンとがキレート錯体の形態で含まれている項1に記載の鉄補給剤。 Item 2. Item 6. The iron supplement according to Item 1, wherein the siderophore and the trivalent iron ion are contained in the form of a chelate complex.
項3. シデロフォアがヒドロキサム酸を含むものである項1又は2に記載の鉄補給剤。 Item 3. Item 3. The iron supplement according to Item 1 or 2, wherein the siderophore contains hydroxamic acid.
項4. 上記キレート錯体がフェリクローム類である項3に記載の鉄補給剤。 Item 4. Item 4. The iron supplement according to Item 3, wherein the chelate complex is ferrichrome.
項5. フェリクローム類がフェリクリシンである項4に記載の鉄補給剤。 Item 5. Item 5. The iron supplement according to Item 4, wherein the ferrichrome is ferriclysin.
項6. シデロフォアと3価鉄イオンとを含む鉄欠乏性貧血の予防又は治療剤。 Item 6. A prophylactic or therapeutic agent for iron deficiency anemia comprising siderophore and trivalent iron ions.
項7. シデロフォアと3価鉄イオンとがキレート錯体の形態で含まれている項6に記載の鉄欠乏性貧血の予防又は治療剤。 Item 7. Item 7. The preventive or therapeutic agent for iron deficiency anemia according to Item 6, wherein the siderophore and trivalent iron ion are contained in the form of a chelate complex.
項8. シデロフォアがヒドロキサム酸を含むものである項6又は7に記載の鉄欠乏性貧血の予防又は治療剤。 Item 8. Item 8. The preventive or therapeutic agent for iron deficiency anemia according to Item 6 or 7, wherein the siderophore contains hydroxamic acid.
項9. 上記キレート錯体がフェリクローム類である項8に記載の鉄欠乏性貧血の予防又は治療剤。 Item 9. Item 9. The preventive or therapeutic agent for iron deficiency anemia according to Item 8, wherein the chelate complex is ferrichrome.
項10. フェリクローム類がフェリクリシンである項9に記載の鉄欠乏性貧血の予防又は治療剤。 Item 10. Item 10. The preventive or therapeutic agent for iron deficiency anemia according to Item 9, wherein the ferrichrome is ferriclysin.
項11. シデロフォアと3価鉄イオンとを含む鉄補給用食品添加剤。 Item 11. A food additive for iron supplementation containing siderophore and trivalent iron ions.
項12. シデロフォアと3価鉄イオンとを含む鉄欠乏性貧血の予防又は改善用食品添加剤。 Item 12. A food additive for preventing or improving iron deficiency anemia, comprising siderophore and trivalent iron ions.
項13. シデロフォアと3価鉄イオンとを含む食品組成物。 Item 13. A food composition comprising siderophore and trivalent iron ions.
項14. シデロフォアと3価鉄イオンとがキレート錯体の形態で含まれている項13に記載の食品組成物。 Item 14. Item 14. The food composition according to Item 13, wherein the siderophore and the trivalent iron ion are contained in the form of a chelate complex.
項15. 固形状の食品組成物中に、シデロフォアと3価鉄イオンとがキレート錯体に換算して0.1〜5mg/g含まれている項13又は14に記載の食品組成物。 Item 15. Item 15. The food composition according to Item 13 or 14, wherein the solid food composition contains 0.1 to 5 mg / g of siderophore and trivalent iron ions in terms of a chelate complex.
項16. 液体状の食品組成物中に、シデロフォアと3価鉄イオンとがキレート錯体に換算して0.05〜10mg/ml含まれている項13又は14に記載の食品組成物。 Item 16. Item 15. The food composition according to item 13 or 14, wherein the liquid food composition contains siderophore and trivalent iron ions in an amount of 0.05 to 10 mg / ml in terms of a chelate complex.
項17. 食品が、酒類、茶類、コーヒー類、スポーツドリンク類、清涼飲料水、乳飲料、及びスープからなる群より選ばれる飲料である項16に記載の食品組成物。 Item 17. Item 17. The food composition according to Item 16, wherein the food is a beverage selected from the group consisting of alcoholic beverages, teas, coffees, sports drinks, soft drinks, milk beverages, and soups.
項18. 鉄補給用の項13〜17のいずれかに記載の食品組成物。 Item 18. Item 18. The food composition according to any one of Items 13 to 17 for iron supplementation.
項19. 鉄欠乏性貧血の予防又は改善用の項13〜17のいずれかに記載の食品組成物。 Item 19. Item 18. The food composition according to any one of Items 13 to 17 for prevention or improvement of iron deficiency anemia.
項20. シデロフォアと3価鉄イオンとを含む、以下の(i)〜(vi)のいずれかの食品組成物。
(i) 鉄を補給する作用を有することを特徴とし、鉄を補給するために用いられる旨の表示を付した食品組成物
(ii) 鉄を補助する作用を有することを特徴とし、鉄を補助するために用いられる旨の表示を付した食品組成物
(iii) 鉄を強化する作用を有することを特徴とし、鉄を強化するために用いられる旨の表示を付した食品組成物
(iv) 鉄を付加する作用を有することを特徴とし、鉄を付加するために用いられる旨の表示を付した食品組成物
(v) 体内の鉄含量を正常に保つ作用を有することを特徴とし、体内の鉄含量を正常に保つために用いられる旨の表示を付した食品組成物
(vi) 体内の鉄不足を解消又は軽減する作用を有することを特徴とし、体内の鉄不足を解消又は軽減するために用いられる旨の表示を付した食品組成物
Item 20. The food composition according to any one of the following (i) to (vi), comprising a siderophore and trivalent iron ions.
(i) A food composition characterized by having an action of replenishing iron and labeled as being used to replenish iron
(ii) A food composition characterized by having an effect of assisting iron and labeled to indicate that it is used to supplement iron
(iii) A food composition characterized by having an effect of strengthening iron and labeled to indicate that it is used to strengthen iron
(iv) A food composition characterized by having an action of adding iron and having a label indicating that it is used for adding iron
(v) A food composition characterized by having a function of maintaining the normal iron content in the body and labeled as being used to maintain the normal iron content in the body
(vi) A food composition characterized by having an action of eliminating or reducing iron deficiency in the body and labeled to indicate that it is used to eliminate or reduce iron deficiency in the body
従来2価鉄イオンの方が生体内への吸収率が高いといわれているが、本発明者により、シデロフォアの3価鉄キレート錯体は、生体内に効率的に吸収されて、血清中の鉄濃度、血中ヘモグロビン濃度、及び肝臓中の貯蔵鉄濃度を増加させることが始めて見出された。 Conventionally, divalent iron ions are said to have a higher absorption rate in the living body. However, the present inventors have effectively absorbed the trivalent iron chelate complex of siderophore into the living body, resulting in iron in serum. It was first found to increase the concentration, blood hemoglobin concentration, and stored iron concentration in the liver.
従って、シデロフォアと3価鉄イオンとを含む組成物は、鉄補給剤、又は鉄欠乏性貧血の予防若しくは治療剤のような医薬製剤として好適に使用できる。また、シデロフォアと3価鉄イオンとを含む食品組成物は、鉄を補給し、鉄欠乏性貧血を予防又は改善することができる。また、シデロフォアと3価鉄イオンとを含む組成物は、食品に添加することにより、食品に、鉄補給作用や鉄欠乏性貧血の予防又は改善作用を与えることができる。 Therefore, a composition containing a siderophore and trivalent iron ions can be suitably used as a pharmaceutical preparation such as an iron supplement or a prophylactic or therapeutic agent for iron deficiency anemia. Moreover, the food composition containing a siderophore and a trivalent iron ion can replenish iron and can prevent or improve iron deficiency anemia. Moreover, the composition containing a siderophore and a trivalent iron ion can give the food an effect of supplementing iron or preventing or improving iron deficiency anemia.
この鉄キレート錯体は、清酒や酒粕のような麹を用いた食品に元来含まれていることから、その安全性は歴史的に証明されている。また後述するように、肝機能・腎機能、体重増加量、摂食量などを低下させず、生体に悪影響を及ぼさないことが判明した。従って、鉄欠乏による各種症状の改善又は治療のためのみならず、予防のために継続的に使用するのに適している。同様に、健常人が摂取する機能性食品又は特定保健用食品などとしても好適である。 Since this iron chelate complex is originally contained in foods using sake such as sake and sake lees, its safety has been proven historically. Further, as will be described later, it has been found that liver function / kidney function, weight gain, food intake, etc. are not decreased and the living body is not adversely affected. Therefore, it is suitable not only for improvement or treatment of various symptoms due to iron deficiency but also for continuous use for prevention. Similarly, it is also suitable as a functional food or a food for specified health use taken by healthy persons.
また、シデロフォアの3価鉄キレート錯体は、麹を用いた食品に元来含まれていることからも分かるように、強い味や臭いを有さないため、医薬品や食品の成分、特に食品添加物として使用し易い。
また、水に溶解し易いため、シロップ剤のような剤型に成型し易く、また液状食品の添加物として使用し易い。また低pHの溶液にも溶解し易いため、ドレッシングのような酸性液状食品にも添加できる。特に、鉄化合物のいくつかはpH=4以下の溶液中で沈殿を生じることがあるが、シデロフォアはこのような酸性溶液中でも高い水溶性を示すことが特長の一つである。
In addition, as can be seen from the fact that siderophore trivalent iron chelate complexes are originally contained in foods using koji, they do not have a strong taste or odor, so they are components of pharmaceuticals and foods, especially food additives. Easy to use as.
Moreover, since it is easy to melt | dissolve in water, it is easy to shape | mold into a dosage form like a syrup agent, and it is easy to use it as an additive of liquid food. Moreover, since it is easy to melt | dissolve also in the solution of low pH, it can add also to acidic liquid foods, such as dressing. In particular, some iron compounds may cause precipitation in a solution having a pH of 4 or less, but one of the features is that the siderophore exhibits high water solubility even in such an acidic solution.
また、高温高圧処理に対して耐性を示し、高温高圧滅菌によっても変性しない又は変性し難いため、医薬品又は食品の成分として使用する場合に、加熱加圧滅菌できる。特に加圧処理に耐性を示すことから、殺菌条件の厳しいレトルト食品への添加剤としても利用できる。さらに、広いpH範囲で熱及び圧力に耐性を示すことから、医薬又は食品に添加する場合に、医薬又は食品の製造工程を制限せず、多様な製造工程が可能になる。 Moreover, since it shows resistance to high-temperature and high-pressure treatment and is not denatured or hardly denatured even by high-temperature and high-pressure sterilization, it can be heat and autoclaved when used as a pharmaceutical or food ingredient. In particular, since it exhibits resistance to pressure treatment, it can also be used as an additive to retort foods with severe sterilization conditions. Furthermore, since it exhibits resistance to heat and pressure in a wide pH range, when it is added to a medicine or food, the production process of the medicine or food is not limited, and various production processes are possible.
さらに、一般に配位子と金属イオンとが別個に存在するより錯体を形成する方が低エネルギー状態、即ち化学的に安定な状態になる。このことから、シデロフォアには鉄イオンが示す過酸化物生成反応の促進作用が見られない。(Metal.Lons Biol.Syst.,Vol35,p37)このように、生体に有害な過酸化物生成を促進しない点でも、シデロフォアは食品や医薬品として利用価値が高い。 Further, in general, a complex is formed in a lower energy state, that is, a chemically stable state, than a ligand and a metal ion are present separately. For this reason, the siderophore does not have the effect of promoting the peroxide formation reaction exhibited by iron ions. (Metal. Lons Biol. Syst., Vol 35, p37) Thus, siderophores are also highly useful as foods and pharmaceuticals in that they do not promote the generation of peroxides that are harmful to living organisms.
さらに、シデロフォアと3価鉄イオンとのキレート錯体は、一般に鉄を不溶化させる食品成分として知られているフィチン酸やタンニン酸のような物質の存在下でも不溶化され難いことから、シデロフォア及び3価鉄イオンはどのような食品に含まれる場合にも、鉄補給効果や鉄欠乏性貧血の予防又は治療効果が効率的に得られる。 Furthermore, siderophores and trivalent iron ions are difficult to be insolubilized even in the presence of substances such as phytic acid and tannic acid, which are generally known as food ingredients that insolubilize iron. Even when ions are contained in any food, an iron supplementation effect and a prevention or treatment effect of iron deficiency anemia can be efficiently obtained.
以下、本発明を詳細に説明する。
(I)鉄補給剤・鉄欠乏性貧血の予防又は治療剤
本発明の鉄補給剤及び鉄欠乏性貧血の予防又は治療剤は、シデロフォアと3価鉄イオンとを含み、特にこれを有効成分として含む。シデロフォアと3価鉄イオンとは別々に含まれていてもよく、又は、キレート錯体として含まれていてもよい。
シデロフォア
「シデロフォア」には、3価鉄イオンをキレート化できる化合物が含まれる。
Hereinafter, the present invention will be described in detail.
(I) Iron supplement / Preventive or therapeutic agent for iron deficiency anemia The iron supplement and the iron deficiency anemia preventive or therapeutic agent of the present invention contain siderophore and trivalent iron ions, and in particular, this is used as an active ingredient. Including. The siderophore and the trivalent iron ion may be included separately or may be included as a chelate complex.
The siderophore “siderophore” includes compounds capable of chelating trivalent iron ions.
シデロフォアの由来は特に限定されず、どのような生物に由来するものであってもよい。多くの微生物は、外界の鉄濃度が低いときに必須成分である鉄を効率的に取り込むためにシデロフォアを生産する。微生物は容易に増殖させることができるため、微生物を用いることによりシデロフォアを容易に大量生産することができる。この点で微生物に由来するシデロフォアが好ましい。さらに、シデロフォア合成酵素群をコードする遺伝子の組換えによりシデロフォアを多量に生産する宿主を容易に作製できる点でも、微生物に由来するシデロフォアが好ましい。 The origin of the siderophore is not particularly limited and may be derived from any organism. Many microorganisms produce siderophores to efficiently take up iron, an essential component, when the external iron concentration is low. Since microorganisms can be easily propagated, siderophores can be easily mass-produced by using microorganisms. In this respect, siderophores derived from microorganisms are preferred. Furthermore, a siderophore derived from a microorganism is also preferable because a host that produces a large amount of siderophore can be easily produced by recombination of genes encoding siderophore synthase groups.
微生物由来のシデロフォアの種類は特に限定されない。例えば、シデロフォアと3価鉄イオンとのキレート錯体として、エンテロバクチン、ビブリオバクチン、アグロバクチン、アングイバクチンのようなカテコール類;コプロゲン、フェリクローム類、フェリオキサミン、N,N',N''―トリアセチルフザリニンCのようなヒドロキサメート類;及びリゾフェリンのようなポリカルボキシレート類などが挙げられる。 The type of siderophore derived from microorganisms is not particularly limited. For example, as a chelate complex of siderophore and trivalent iron ions, catechols such as enterobactin, vibriobactin, agrobactin and anguibactin; coprogen, ferrichromes, ferrioxamine, N, N ′, N ″ — And hydroxamates such as triacetyl fusarinin C; and polycarboxylates such as lysoferrin.
特に、鉄キレート力の点で、ヒドロキサメート類(ヒドロキサム酸を含むシデロフォア)が好ましい。その中でも安定性の点で、環状であるフェリクローム類がより好ましい。 In particular, hydroxamates (siderophores containing hydroxamic acid) are preferable in terms of iron chelating power. Among them, cyclic ferrichromes are more preferable from the viewpoint of stability.
フェリクローム類は、3個のヒドロキサム酸を含む環状ペプチド化合物の総称であり、下記一般式(1)で表される化合物を含む。 Ferrichromes are a general term for cyclic peptide compounds containing three hydroxamic acids, and include compounds represented by the following general formula (1).
一般式(1)の化合物の中では、フェリクローム、ジグリシルフェリクローム、フェリクリシン、フェリクロームC、フェリクロシン、アスペルクロームD1、アスペルクロームB1、フェリブリン、フェリロジン、フェリクロームA、デス(ジセリルグリシル)フェリロジン(フェリロジンにおいて=Ser−Ser−Gly−を除いた化合物)が好ましく、フェリクリシンが最も好ましい。
Among the compounds of the general formula (1), ferrichrome, diglycyl ferrichrome, ferriclicin, ferrichrome C, ferricrosin, asperchrome D1, asperchrome B1, ferribrin, ferrilozin, ferrichrome A, des (dicerylglycyl) ferrirosin ( In ferrirosin, = compound except Ser-Ser-Gly-) is preferred, and ferriclysin is most preferred.
これらの化合物の一般式(1)における官能基であるR1〜R5を以下の表1にまとめて示す。 R 1 to R 5 which are functional groups in the general formula (1) of these compounds are summarized in Table 1 below.
本発明において、シデロフォアは、天然型シデロフォアの他、第二鉄のキレート化作用を有する天然型シデロフォアの誘導体も使用できる。天然型シデロフォアの誘導体としては、アセチル化、ニトロ化したものや、アミノ酸の一部が置換されたもの等が挙げられる。 In the present invention, as a siderophore, a natural siderophore or a derivative of a natural siderophore having a chelating action of ferric iron can be used. Examples of natural siderophore derivatives include acetylated and nitrated derivatives, and amino acid partially substituted amino acids.
シデロフォアは、生物から回収することにより製造できる。生物を鉄制限下で生育させると、鉄を含まないデフェリ体(シデロフォア)が生成される。このデフェリ体に鉄を加えることにより通常3価鉄イオンをキレート化した錯体となる。生物から回収されたシデロフォアは粗標品のままであってもよく、精製されたものであってもよい。 Siderophores can be produced by recovery from living organisms. When an organism is grown under iron restriction, a deferri body (siderophore) containing no iron is produced. By adding iron to this deferiated body, a complex obtained by chelating trivalent iron ions is usually obtained. The siderophore recovered from the organism may remain as a crude sample or may be purified.
シデロフォアの精製は、公知の精製方法、例えばイオン交換、疎水、ゲルろ過、アフィニティのような各種クロマトグラフィー等により行えばよい。例えば、糸状菌からシデロフォアを回収する場合は、液体培養して上清中に生産されたものを回収してもよく、固体培養して固体培養物から水又は緩衝液を用いて抽出した抽出液から回収してもよい。いずれにしても本発明の鉄補給剤及び鉄欠乏性貧血の予防又は治療剤には、例えば生物由来の夾雑物が含まれる場合がある。 The siderophore may be purified by a known purification method such as ion exchange, hydrophobicity, gel filtration, various chromatography such as affinity. For example, when recovering siderophores from filamentous fungi, the liquid culture may be used to recover the product produced in the supernatant, or the solid solution is extracted from the solid culture using water or buffer. May be recovered from. In any case, the iron supplement and the prophylactic or therapeutic agent for iron deficiency anemia of the present invention may contain biological impurities, for example.
またシデロフォアは、市販品を購入することもできる。また、これらのシデロフォアの混合物であってもよい。
フェリクリシン
フェリクリシンを構成する配位子であるデフェリフェリクリシンは、麹造り(固体培養)においてアスペルギルス・オリゼが多量に生産することが知られているフェリクローム類の1種である。アスペルギルス・オリゼが生産するフェリクローム類の殆どがデフェリフェリクリシンである。デフェリフェリクリシンは3価鉄イオンをキレート化してフェリクリシンになる。
Siderophores can also be purchased commercially. Moreover, the mixture of these siderophores may be sufficient.
Deferlifericin, which is a ligand constituting ferriclysin, is one of the ferrichromes known to be produced in large quantities by Aspergillus oryzae in koji making (solid culture). Most of the ferrichromes produced by Aspergillus oryzae are deferlifericins. Deferifericin is chelated to trivalent iron ions to become ferriclysin.
デフェリフェリクリシンは、例えば以下の方法でアスペルギルス・オリゼから回収することができる。即ち、アスペルギルス・オリゼを培養する培地として、例えばポテトデキストロース培地(ニッスイ社)または最少培地(2%グルコース(又はスターチ)、0.3%NaNO3、0.2%KCl、0.1%K2HPO4、0.05%MgSO4、pH6.0)等を使用できる。培地は、固体培地でも液体培地でもよいが、デフェリフェリクリシンを回収し易い点で、液体培地を使用することが好ましい。また、米麹のような固体培地も、そこからデフェリフェリクリシンを回収、精製することなく、そのまま食品組成物に使用できる点で好ましい。 Deferifericin can be recovered from Aspergillus oryzae, for example, by the following method. That is, as a medium for culturing Aspergillus oryzae, for example, potato dextrose medium (Nissui) or minimal medium (2% glucose (or starch), 0.3% NaNO 3 , 0.2% KCl, 0.1% K 2 HPO 4 , 0.05% MgSO 4 , pH 6.0) and the like can be used. The medium may be a solid medium or a liquid medium, but it is preferable to use a liquid medium in terms of easy recovery of deferlifericin. Further, a solid medium such as rice bran is also preferable in that it can be used as it is in a food composition without recovering and purifying deferifericin from there.
培養温度は、アスペルギルス・オリゼの生育可能温度範囲であればよく、例えば25〜42℃程度が挙げられる。培養時間は、その他の条件によって異なるが、通常2〜7日間程度とすればよい。 The culture temperature should just be the temperature range which can grow Aspergillus oryzae, for example, about 25-42 degreeC is mentioned. Although the culture time varies depending on other conditions, it may normally be about 2 to 7 days.
培養終了後、菌体をろ過後、培養液からフェリクリシンを回収する。さらに、この培養上清を、公知のタンパク質精製方法、例えばイオン交換、疎水、ゲルろ過、アフィニティなどの各種クロマトグラフィーに供することにより精製デフェリフェリクリシンが得られる。
3価鉄イオン
シデロフォア(デフェリ体)と3価鉄イオンとが混合されることにより、通常、速やかにキレート錯体が生成する。本発明の鉄補給剤又は鉄欠乏性貧血の予防若しくは治療剤が投与されると、3価鉄イオンは、シデロフォアとのキレート錯体の形態で、血中ヘモグロビン濃度、血清中鉄濃度、及び肝臓中鉄濃度を効果的に向上させる。
After completion of the culture, the bacterial cells are filtered, and ferriclysin is recovered from the culture solution. Further, the purified supernatant is subjected to a known protein purification method, for example, various chromatography such as ion exchange, hydrophobicity, gel filtration, affinity, etc., to obtain purified deferlifericin.
When a trivalent iron ion siderophore (deferri form) and a trivalent iron ion are mixed, a chelate complex is usually rapidly formed. When the iron supplement of the present invention or an agent for preventing or treating iron deficiency anemia is administered, trivalent iron ions are in the form of a chelate complex with siderophore, blood hemoglobin concentration, serum iron concentration, and liver Effectively improve iron concentration.
鉄補給剤及び鉄欠乏性貧血の予防又は治療剤中に含まれるシデロフォアと3価鉄イオンとの比率は、モル比で、通常1〜5:1程度が好ましく、1〜2:1程度がより好ましい。シデロフォアと3価鉄イオンとは同モル程度含まれることが通常最も好ましい。
製造方法
本発明の鉄補給剤及び鉄欠乏性貧血の予防又は治療剤は、シデロフォアと3価鉄イオンとを混合すること、又は、組み合わせることにより製造できる。
製剤
本発明の鉄補給剤及び鉄欠乏性貧血の予防又は治療剤において、シデロフォア及び3価鉄イオン、好ましくはこれらのキレート錯体は、薬学的に許容される各種担体(賦形剤、結合剤、崩壊剤、潤沢剤、付湿剤等が含まれる)と配合して、適当な製剤とされる。また、この製剤には慣用の添加剤が含まれていてよい。
The ratio of siderophore and trivalent iron ions contained in the iron supplement and the preventive or therapeutic agent for iron deficiency anemia is preferably about 1 to 5: 1 and more preferably about 1 to 2: 1 in terms of molar ratio. preferable. It is usually most preferable that the siderophore and the trivalent iron ion are contained in the same mole.
Production Method The iron supplement and the iron-deficiency anemia prevention or treatment agent of the present invention can be produced by mixing or combining siderophores and trivalent iron ions.
Formulations In the iron supplement of the present invention and the prophylactic or therapeutic agent for iron deficiency anemia, siderophores and trivalent iron ions, preferably these chelate complexes, are pharmaceutically acceptable various carriers (excipients, binders, (Including disintegrants, lubricants, moisturizers, etc.). The formulation may also contain conventional additives.
製剤形態は、特に限定されず、例えば錠剤、丸剤、カプセル剤、散剤、顆粒剤、シロップ剤等の経口投与剤;注射剤、点滴剤、外用剤、座剤等の非経口投与剤などの各種製剤形態を挙げることができる。経口投与剤の方が、非経口投与剤に比べて患者への負担が小さいために、使用し易い。この点、シデロフォア及び3価鉄イオンは、これらを組み合わせて経口投与する場合に、効果的に血清中鉄濃度、血中鉄濃度、及び肝臓中貯蔵鉄濃度などを増加させることができるため、経口投与剤の形態で好適に使用できる。 The form of the preparation is not particularly limited. For example, oral administration agents such as tablets, pills, capsules, powders, granules, syrups, etc .; parenteral administration agents such as injections, drops, external preparations, suppositories, etc. Various preparation forms can be mentioned. Orally administered agents are easier to use because they place less burden on patients than parenterally administered agents. In this regard, siderophore and trivalent iron ions can effectively increase serum iron concentration, blood iron concentration, liver stored iron concentration, and the like when these are orally administered in combination. It can be suitably used in the form of an administration agent.
賦形剤としては、公知のものを広く使用でき、例えば、乳糖、ショ糖、ブドウ糖等の各種の糖類、バレイショデンプン、コムギデンプン、トウモロコシデンプン等の各種デンプン類、結晶セルロース等の各種セルロース類、無水リン酸水素カルシウム、炭酸カルシウム等の各種無機塩類等が挙げられる。 As the excipient, known ones can be widely used, for example, various sugars such as lactose, sucrose and glucose, various starches such as potato starch, wheat starch and corn starch, various celluloses such as crystalline cellulose, Examples include various inorganic salts such as anhydrous calcium hydrogen phosphate and calcium carbonate.
結合剤としては、公知のものを広く使用でき、例えば、結晶セルロース、プルラン、アラビアゴム、アルギン酸ナトリウム、ポリビニルピロリドン、マクロゴール等が挙げられる。 As the binder, known ones can be widely used, and examples thereof include crystalline cellulose, pullulan, gum arabic, sodium alginate, polyvinyl pyrrolidone, macrogol and the like.
崩壊剤としては、公知のものを広く使用でき、例えば、カルボキシメチルセルロース、カルボキシメチルセルロースカルシウム、ヒドロキシプロピルセルロース、ヒドロキシプロピルスターチ、デンプン、アルギン酸ナトリウム等が挙げられる。 As the disintegrant, known ones can be widely used, and examples thereof include carboxymethyl cellulose, carboxymethyl cellulose calcium, hydroxypropyl cellulose, hydroxypropyl starch, starch, sodium alginate and the like.
潤沢剤としては、ステアリン酸マグネシウム、タルク、硬化油などが挙げられる。 Examples of the lubricant include magnesium stearate, talc, and hardened oil.
付湿剤としては、公知のものを広く使用でき、例えば、ココナッツ油、オリーブ油、ゴマ油、落花生油、大豆リン脂質、グリセリン、ソルビトールなどが挙げられる。 Known humectants can be widely used, and examples thereof include coconut oil, olive oil, sesame oil, peanut oil, soybean phospholipid, glycerin, and sorbitol.
製剤中のシデロフォア及び3価鉄イオンの含有量は、シデロフォアの種類、投与経路、投与対象又は患者の年齢、体重、症状等によって異なり一概に規定できないが、3価鉄キレート錯体の形態での1日投与量が通常20〜170mg程度、より好ましくは40〜80mg程度になる量とすればよい。1日1回投与する場合は、1製剤中にこの量が含まれていればよく、1日3回投与する場合は、1製剤中にこの3分の1量が含まれていればよい。 The content of siderophore and trivalent iron ions in the preparation varies depending on the type of siderophore, administration route, administration subject or patient's age, body weight, symptoms, etc., but cannot be specified unconditionally, but in the form of trivalent iron chelate complex 1 The daily dose is usually about 20 to 170 mg, more preferably about 40 to 80 mg. When it is administered once a day, it is sufficient that this amount is contained in one preparation, and when it is administered three times a day, this one-third amount may be contained in one preparation.
また、錠剤、丸剤、カプセル剤、散剤、顆粒剤のような固形製剤の場合は、製剤中にシデロフォアと3価鉄とがキレート錯体に換算して5〜30重量%程度含まれていればよい。また、シロップ剤のような液体製剤の場合は、シデロフォアと3価鉄とがキレート錯体に換算して0.2〜1重量%程度含まれていればよい。また、注射剤、点滴剤の場合は、シデロフォアと3価鉄とがキレート錯体に換算して0.4〜2重量%程度含まれていればよい。外用剤の場合は、シデロフォアと3価鉄とがキレート錯体に換算して1〜10重量%程度含まれていればよい。座剤の場合は、シデロフォアと3価鉄とがキレート錯体に換算して2〜20重量%程度含まれていればよい。上記の含有量の範囲であれば、鉄補給効果、又は鉄欠乏性貧血の予防又は治療効果が十分に得られるとともに、副作用が現れることがない。 Moreover, in the case of solid preparations such as tablets, pills, capsules, powders, and granules, siderophores and trivalent iron are contained in the preparation in an amount of about 5 to 30% by weight in terms of a chelate complex. Good. Further, in the case of a liquid preparation such as a syrup, siderophore and trivalent iron may be contained in an amount of about 0.2 to 1% by weight in terms of a chelate complex. In the case of injections and drops, siderophore and trivalent iron may be contained in an amount of about 0.4 to 2% by weight in terms of a chelate complex. In the case of an external preparation, siderophore and trivalent iron may be contained in an amount of about 1 to 10% by weight in terms of a chelate complex. In the case of a suppository, siderophore and trivalent iron may be contained in an amount of about 2 to 20% by weight in terms of a chelate complex. If it is the range of said content, while an iron supplementation effect or the prevention or treatment effect of iron deficiency anemia will fully be acquired, a side effect will not appear.
シデロフォアは高温(例えば120℃程度)高圧(例えば200kPa程度)処理によっても変性しない又は変性し難いことから、医薬組成物の成分として用いる場合に、加熱加圧滅菌できるという利点を有する。またシデロフォアは、従来麹を用いた食品に含まれていることから、その安全性が歴史的に確認されており、医薬組成物の成分として使用する場合に副作用が生じない又は適性用量では副作用が生じない。
(II)食品添加剤
本発明の食品添加剤は、シデロフォアと3価鉄イオンとを含む添加剤である。これらはキレート錯体の形態で含まれていてもよい。この添加剤は、食品に、鉄補給作用、又は鉄欠乏性貧血の予防若しくは改善作用を与えるための添加剤として好適に使用できる。
Siderophores have the advantage of being heat and autoclavable when used as a component of a pharmaceutical composition because they are not denatured or hardly denatured by high temperature (eg, about 120 ° C.) and high pressure (eg, about 200 kPa) treatment. Since siderophore has been included in foods that have been used in traditional cocoons, its safety has been confirmed historically, and when used as a component of a pharmaceutical composition, side effects do not occur or at appropriate doses, side effects are not present. Does not occur.
(II) Food additive The food additive of the present invention is an additive containing siderophore and trivalent iron ions. These may be included in the form of a chelate complex. This additive can be suitably used as an additive for giving food an iron supplementing action or an iron deficiency anemia preventing or improving action.
食品添加剤には、シデロフォア及び3価鉄イオンの他に、糖類、デンプン類、セルロース、ステアリン酸マグネシウム、植物油などの担体や、添加剤が含まれていてもよい。食品添加剤中に担体や添加剤が含まれる場合のシデロフォア及び3価鉄イオンの含有量は、キレート錯体に換算して、固形製剤の場合は0.4〜4重量%程度とすることができ、液体製剤の場合は0.04〜0.4重量%程度とすることができる。シデロフォアと3価鉄イオンとの好ましい比率は、医薬製剤について説明した通りである。 In addition to siderophore and trivalent iron ions, the food additive may contain carriers such as sugars, starches, cellulose, magnesium stearate, vegetable oil, and additives. The content of siderophore and trivalent iron ions in the case where a food additive is included in the food additive can be about 0.4 to 4% by weight in the case of a solid preparation in terms of a chelate complex. In the case of a liquid preparation, it can be about 0.04 to 0.4% by weight. The preferred ratio of siderophore to trivalent iron ions is as described for the pharmaceutical preparation.
食品添加剤の剤形は、特に限定されないが、例えば、粉状、顆粒状、液体状のような剤形とすることができる。
(III)食品組成物
本発明の食品組成物は、シデロフォアと3価鉄イオンとを、好ましくはキレート錯体として含む組成物である。
The dosage form of the food additive is not particularly limited. For example, it may be a powder form, a granule form, or a liquid form.
(III) Food Composition The food composition of the present invention is a composition containing siderophore and trivalent iron ions, preferably as a chelate complex.
この食品組成物は、鉄補給(言い換えれば、鉄補助、鉄強化、鉄付加、体内鉄含量を正常に保つこと、体内の鉄不足の解消又は軽減)作用や、鉄欠乏性貧血の予防又は改善作用を有することから、これらの目的で用いられる旨の表示を付した食品組成物とすることができる。この食品組成物は、機能性食品、又は特定保健用食品などとして好適に使用できる。この場合、上記錯体は有効成分として含まれている。 This food composition has the effect of supplementing iron (in other words, iron supplementation, iron strengthening, iron addition, maintaining normal iron content, eliminating or reducing iron deficiency in the body) and preventing or improving iron deficiency anemia. Since it has an effect | action, it can be set as the foodstuff composition which attached | subjected the indication to be used for these objectives. This food composition can be suitably used as a functional food or a food for specified health use. In this case, the complex is contained as an active ingredient.
シデロフォアの3価鉄錯体は従来清酒に含まれている成分であり、食品の風味を損ねるような味や匂いを有さない。従って、食品の種類は特に限定されない。例えば、飴、ガム、ケーキ、パイ、クッキー、クラッカー、ゼリー、チョコレート、プディング、アイスクリーム、ポテトチップス、羊羹、煎餅、饅頭、中華饅頭のような菓子;酒類、茶類、コーヒー類、スポーツドリンク類、清涼飲料水、スープ、乳飲料のような飲料;ヨーグルト、バター、チーズのような乳製品;ハム、ソーセージ、蒲鉾、竹輪のような練り物;ソース、ドレッシング、マヨネーズ、醤油、味噌、酢、味醂、トマト加工品(ケチャップ、トマトペースト、トマトピューレ)、カレールウ、酒粕、顆粒だしのような調味料;ふりかけ、漬物、佃煮、塩昆布のような常備惣菜類;惣菜;麺、米飯、粥のような主食類などが挙げられる。 A trivalent iron complex of siderophore is a component conventionally contained in sake, and does not have a taste or smell that impairs the flavor of food. Therefore, the type of food is not particularly limited. For example, sweets such as candy, gum, cake, pie, cookies, crackers, jelly, chocolate, pudding, ice cream, potato chips, sheep candy, rice crackers, buns, Chinese buns; liquors, teas, coffees, sports drinks Beverages such as soft drinks, soups and milk drinks; dairy products such as yogurt, butter and cheese; kneaded products such as ham, sausage, strawberries and bamboo rings; , Processed tomato products (ketchup, tomato paste, tomato puree), seasoning such as carreau, sake lees, granule soup; regular prepared vegetables such as sprinkles, pickles, boiled boiled fish, salt kelp; side dish; noodles, rice Major staple foods.
シデロフォアは、高い水溶性を有しているため、飲料や、ソース、ドレッシング、醤油、酢、味醂のような液状調味料のような液状食品が好ましく、酒類、茶類、コーヒー類、スポーツドリンク類、清涼飲料水、乳飲料、及びスープのような飲料がより好ましい。最も好ましいのは、酒類、茶類、コーヒー類、スポーツドリンク類、及び清涼飲料水である。また、鉄化合物の水溶性が低くなることがある低pH条件下でも高い水溶性を示すため、マヨネーズやドレッシングのような液状酸性食品の添加剤としても好適に使用できるという利点がある。また前述したように高温高圧処理に耐えるため、本発明の鉄補給剤を添加した食品の加熱加圧滅菌を行えるとともに、レトルト処理のような特殊な製造工程を経ることもできる。さらにシデロフォアは、従来麹を用いた食品に含まれていることから、その安全性が歴史的に確認されている点でも、食品添加物として好適である。 Since siderophores have high water solubility, liquid foods such as beverages and liquid seasonings such as sauces, dressings, soy sauce, vinegar and miso are preferred. Alcoholic beverages, teas, coffees, sports drinks Beverages such as soft drinks, milk drinks, and soups are more preferred. Most preferred are liquors, teas, coffees, sports drinks, and soft drinks. Further, since the water solubility of the iron compound is low, it exhibits high water solubility even under low pH conditions, so that it can be suitably used as an additive for liquid acidic foods such as mayonnaise and dressings. In addition, as described above, in order to withstand high-temperature and high-pressure treatment, foods to which the iron supplement of the present invention is added can be subjected to heat and pressure sterilization, and a special manufacturing process such as retort treatment can be performed. Furthermore, since siderophore is conventionally contained in foods using koji, it is also suitable as a food additive in that its safety has been confirmed historically.
食品組成物中のシデロフォア及び3価鉄イオンの含有量は、シデロフォアの種類、投与対象又は患者の年齢、体重、症状等によって異なり一概に規定できないが、キレート錯体の形態での1日摂取量が、20〜170mg程度、特に40〜80mg程度になる量とすればよい。 The content of siderophore and trivalent iron ions in the food composition differs depending on the type of siderophore, the subject of administration or the age, weight, symptoms, etc. of the patient, but cannot be specified unconditionally, but the daily intake in the form of a chelate complex The amount may be about 20 to 170 mg, particularly about 40 to 80 mg.
また、食品中のシデロフォア及び3価鉄イオンの濃度は、食品の種類などによって異なるが、固体状食品の場合は、キレート錯体に換算して0.1〜5mg/g程度が好ましく、0.2〜3mg/g程度がより好ましく、0.25〜1.5mg/g程度がさらにより好ましい。液状食品の場合は、キレート錯体に換算して0.05〜10mg/ml程度が好ましく、0.1〜5mg/ml程度がより好ましく、0.2〜1mg/ml程度がさらに好ましい。食品の形態によって異なるが、一般的な固形状食品の1回の摂取量は10〜50g程度であり、液体形状の食品の1回摂取量は50ml〜500ml程度であることから、上記の摂取量で1日に必要な鉄イオンを補給することができる。上記範囲であれば、十分な鉄補給効果、又は鉄欠乏性貧血の予防若しくは改善効果が得られるとともに、鉄過剰症になる恐れがない。 The concentration of siderophore and trivalent iron ions in the food varies depending on the type of food, but in the case of solid food, it is preferably about 0.1 to 5 mg / g in terms of chelate complex, About 3 mg / g is more preferable, and about 0.25-1.5 mg / g is even more preferable. In the case of liquid food, it is preferably about 0.05 to 10 mg / ml, more preferably about 0.1 to 5 mg / ml, and further preferably about 0.2 to 1 mg / ml in terms of chelate complex. Although it varies depending on the form of the food, the intake amount of a general solid food is about 10 to 50 g, and the intake amount of a liquid food is about 50 to 500 ml. The necessary iron ions can be replenished in a day. If it is the said range, while sufficient iron supplementation effect or the prevention or improvement effect of iron deficiency anemia will be acquired, there is no possibility of becoming iron overload.
液体状食品の中でも、酒類、特に日本酒にシデロフォア及び3価鉄イオンが上記比率で含まれることにより、鉄欠乏性貧血に有効であり、かつ副作用を生じず、さらに飲むときに不快感を抱かせることがない。 Among liquid foods, alcoholic beverages, especially Japanese sake, contain siderophore and trivalent iron ions in the above ratios, so that they are effective for iron deficiency anemia, have no side effects, and make you feel uncomfortable when you drink. There is nothing.
本発明の食品組成物には、食品組成物の調製に当たり慣用されている各種添加剤を添加配合することができる。添加剤としては、例えば、安定化剤、pH調整剤、糖類、甘味料、香料、各種ビタミン類、ミネラル類、抗酸化剤、賦形剤、可溶化剤、結合剤、滑沢剤、懸濁剤、湿潤剤、皮膜形成物質、矯味剤、矯臭剤、着色料、保存剤等を例示することができる。 In the food composition of the present invention, various additives conventionally used in the preparation of food compositions can be added and blended. Examples of additives include stabilizers, pH adjusters, sugars, sweeteners, fragrances, various vitamins, minerals, antioxidants, excipients, solubilizers, binders, lubricants, and suspensions. Examples include agents, wetting agents, film-forming substances, flavoring agents, flavoring agents, colorants, preservatives and the like.
また、本発明の食品組成物は、鉄補給のため、又は、鉄欠乏性貧血の予防若しくは改善のための栄養補助食品、即ちサプリメントとしても好適に使用できる。この場合の食品組成物中には、シデロフォア及び3価鉄イオンの他に、サプリメントの担体として公知の成分が含まれていればよい。このような担体として、例えば糖類、デンプン類、セルロース、ステアリン酸マグネシウム、植物油が挙げられる。 The food composition of the present invention can also be suitably used as a dietary supplement, ie, a supplement, for iron supplementation or for prevention or improvement of iron deficiency anemia. In this case, the food composition only needs to contain components known as a supplement carrier in addition to siderophore and trivalent iron ions. Examples of such carriers include sugars, starches, cellulose, magnesium stearate, and vegetable oils.
サプリメント中のシデロフォア及び3価鉄イオンの含有量は、キレート錯体に換算して、30mg〜300mg程度であることが好ましく、60mg〜200mg程度であることがより好ましい。上記範囲であれば、十分に鉄補給効果や鉄欠乏性貧血の予防若しくは改善効果が得られるとともに、多すぎて副作用が現れることがない。 The content of the siderophore and trivalent iron ions in the supplement is preferably about 30 mg to 300 mg, more preferably about 60 mg to 200 mg in terms of chelate complex. If it is the said range, while being able to acquire the iron replenishment effect and the prevention or improvement effect of iron deficiency anemia sufficiently, there are too many side effects.
サプリメントの形状は特に限定されないが、例えば、錠剤状、粉状、顆粒状などの形状が挙げられる。
(IV)鉄補給方法・鉄欠乏性貧血の予防、改善又は治療方法
シデロフォアの3価鉄キレート錯体は、生体内への鉄の吸収率が高いため、シデロフォアと3価鉄イオンとをヒトに投与することにより、鉄を補給し、鉄の欠乏による、貧血、運動・学習能力低下、免疫力低下等を効果的に予防、改善又は治療することができる。特に、鉄欠乏性貧血を効果的に予防、改善又は治療できる。
Although the shape of a supplement is not specifically limited, For example, shapes, such as a tablet form, powder form, and granular form, are mentioned.
(IV) Iron supplementation method / Prevention, improvement or treatment method of iron deficiency anemia Since the trivalent iron chelate complex of siderophore has high absorption rate of iron into the living body, siderophore and trivalent iron ion are administered to humans. By doing so, it is possible to effectively prevent, improve, or treat anemia, reduced motor / learning ability, reduced immunity, etc. due to iron deficiency. In particular, iron deficiency anemia can be effectively prevented, ameliorated, or treated.
鉄補給剤及び鉄補給用組成物の投与対象は、鉄欠乏による症状が現れているヒト又は健常人のいずれであってもよい。また、鉄が欠乏し易い成長期の子供や成人女性も好適な投与対象である。 The administration target of the iron supplement and the iron supplement composition may be either a human or a healthy person who has symptoms due to iron deficiency. In addition, growing children and adult women who are easily deficient in iron are also suitable administration subjects.
投与量は、シデロフォアの種類、投与対象の症状、年齢、体重などによって異なるが、キレート錯体の形態での1日投与量が20〜170mg程度、特に40〜80mg程度となる量を1日1回又は数回に分けて投与すればよい。 The dose varies depending on the type of siderophore, the symptom of the administration subject, age, weight, etc., but the daily dose in the form of a chelate complex is about 20 to 170 mg, particularly about 40 to 80 mg once a day. Or it may be administered in several divided doses.
投与経路は、経口又は非経口のいずれであってもよいが、経口投与する場合にも効果的に血清中鉄濃度を向上させることができることから、簡便な経口投与が好ましい。
実施例
以下、本発明を実施例及び試験例を示してより詳細に説明するが、本発明はこれらの実施例に限定されない。
フェリクリシンの調製
米麹を水で抽出した抽出液(デフェリフェリクリシン含有)に、デフェリフェリクリシンと等モルの塩化第二鉄を加えてフェリクリシン溶液を作製した後、限外濾過膜を用いて分子量5000以上のタンパク質などの高分子を除去し、ろ液をカラムクロマトにより濃縮した。フェリクリシンは430nmに極大吸収を示す性質が知られている(Agr.Biol.Chem.,Vol.31,No.12,p1482)ため、上記の手法で調製された溶液をHPLC分析し、430nmの吸収を示す物質の大半がフェリクリシンであることを確認した。
The administration route may be either oral or parenteral, but simple oral administration is preferable because the serum iron concentration can be effectively improved even in oral administration.
EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples and test examples, but the present invention is not limited to these examples.
Preparation of ferriclysin <br/> After adding ferricricin solution and equimolar ferric chloride to the extract of rice bran extracted with water (containing deferriferricricin), Polymers such as proteins having a molecular weight of 5000 or more were removed using an outer filtration membrane, and the filtrate was concentrated by column chromatography. Since ferriclysin is known to have a maximum absorption at 430 nm (Agr. Biol. Chem., Vol. 31, No. 12, p1482), the solution prepared by the above method was analyzed by HPLC. It was confirmed that most of the substance showing absorption was ferriclysin.
ラットに与えた飼料の鉄濃度はフェリクリシン、水溶性ヘム鉄、クエン酸第二鉄すべてHPLCでなく原子吸光により35ppmに調製した。フェリクリシンのHPLC分析は、430nmに吸収を示す物質がほとんどフェリクリシンであったことを示す定性分析である。 The iron concentration of the diet given to the rats was adjusted to 35 ppm by atomic absorption, not by HPLC, of ferriclysin, water-soluble heme iron and ferric citrate. The HPLC analysis of ferriclysin is a qualitative analysis showing that the substance that absorbs at 430 nm was mostly ferriclysin.
4週齢のSD系雄ラット15匹に、鉄欠乏飼料を35日間自由摂取させて、血液中の平均ヘモグロビン値が6.5g/dlまで低下した鉄欠乏性貧血ラットを作製した。また、対照群の4週齢のSD系雄ラット5匹には鉄含有飼料1を与えた。対照群に与えた鉄含有飼料1の鉄源は通常ラットの飼育飼料に使用されているクエン酸第二鉄であり、その鉄含量はラットの生育に最適とされている35ppmである。 Fifteen 4-week-old male SD rats were allowed to freely take an iron-deficient diet for 35 days to produce iron-deficient anemia rats in which the average hemoglobin value in the blood decreased to 6.5 g / dl. In addition, five 4-week-old SD male rats in the control group were fed with iron-containing feed 1. The iron source of the iron-containing feed 1 given to the control group is ferric citrate, which is usually used for breeding feed of rats, and its iron content is 35 ppm, which is optimal for the growth of rats.
鉄欠乏性貧血にした後に、それぞれ鉄含有飼料1(クエン酸第二鉄)、鉄含有飼料2(ヘム鉄)及び鉄含有飼料3(フェリクリシン)を投与した各群のラットについて、飼料の投与前と投与3週間後に採血をそれぞれ行い、常法により血液中のヘモグロビン濃度を測定した。また、当初から鉄含有飼料1(クエン酸第二鉄)を投与した対照群ラットについては、鉄含有飼料1を投与した。結果を以下の表7に示す。表7中の値は、各群5匹のヘモグロビン濃度の平均値±標準偏差値を示す。
血清中鉄濃度の測定
また、鉄含有飼料投与後に各群ラットから全採血した血液より血清を調整し、常法に従い血清鉄濃度を測定した。結果を以下の表8に示す。表8中の値は、各群5匹の血清鉄濃度の平均値±標準偏差値である。
Measurement of serum iron concentration Serum was prepared from blood collected from each group of rats after administration of an iron-containing feed, and the serum iron concentration was measured according to a conventional method. The results are shown in Table 8 below. The values in Table 8 are the mean value ± standard deviation value of the serum iron concentration of 5 animals in each group.
肝臓中鉄濃度の測定
鉄欠乏性貧血にした後に、それぞれ鉄含有飼料1(クエン酸第二鉄)、鉄含有飼料2(ヘム鉄)及び鉄含有飼料3(フェリクリシン)を投与した群のラット、及び、当初から鉄含有飼料1(クエン酸第二鉄)を摂食させた対照群ラットについて、鉄含有飼料の3週間の摂食終了後時に肝臓を脱血潅流して摘出し、重量を測定した後、凍結乾燥を行った。また、乾燥肝臓を灰化し原子吸光に供して鉄濃度を測定した。さらに、肝臓の水分含量を計算し、乾燥肝臓における鉄濃度と肝臓の水分含量とから生体内の肝臓に貯蔵されている鉄濃度を求めた。結果を以下の表9に示す。表9中の値は、各群5匹のラットについての肝臓鉄濃度の平均値±標準偏差である。
Measurement of iron concentration in liver After iron deficiency anemia, iron-containing feed 1 (ferric citrate), iron-containing feed 2 (heme iron) and iron-containing feed 3 (ferriclysin) were administered, respectively. And the control group rats fed with iron-containing feed 1 (ferric citrate) from the beginning, the liver was deperfused and removed at the end of 3 weeks of feeding the iron-containing feed. Then, after measuring the weight, it was freeze-dried. In addition, the dried liver was ashed and subjected to atomic absorption to measure the iron concentration. Furthermore, the water content of the liver was calculated, and the iron concentration stored in the liver in vivo was determined from the iron concentration in the dry liver and the water content of the liver. The results are shown in Table 9 below. The values in Table 9 are the mean value of liver iron concentration ± standard deviation for 5 rats in each group.
肝臓機能・腎臓機能に与える影響の検討
鉄欠乏性貧血にした後に、それぞれ鉄含有飼料1(クエン酸第二鉄)、鉄含有飼料2(ヘム鉄)及び鉄含有飼料3(フェリクリシン)を投与した各群のラット、及び、当初から鉄含有飼料1(クエン酸第二鉄)を摂食させた対照群ラットについて、常法に従い血清中のタンパク質濃度、ALT(アラニンアミノトランスフェラーゼ)濃度、AST(アスパラギン酸アミノトランスフェラーゼ)濃度、クレアチニン濃度を測定した。結果を以下の表10に示す。表10中の値は、各群5匹のラットについての平均値±標準偏差である。aを付した数値とbを付した数値との間には有意差があることを示す。
Examination of effects on liver and kidney functions <br/> After iron deficiency anemia, iron-containing feed 1 (ferric citrate), iron-containing feed 2 (heme iron) and iron-containing feed 3 (ferri) In each group of rats administered with chrysin) and a control group rat fed with iron-containing feed 1 (ferric citrate) from the beginning, serum protein concentration, ALT (alanine aminotransferase) according to a conventional method Concentration, AST (aspartate aminotransferase) concentration, and creatinine concentration were measured. The results are shown in Table 10 below. The values in Table 10 are mean ± standard deviation for 5 rats in each group. It shows that there is a significant difference between the numerical value with a and the numerical value with b.
体重増加量・摂食量に及ぼす影響の検討
鉄欠乏性貧血にした後に、それぞれ鉄含有飼料1(クエン酸第二鉄)、鉄含有飼料2(ヘム鉄)及び鉄含有飼料3(フェリクリシン)を投与した各群のラット、及び、当初から鉄含有飼料1(クエン酸第二鉄)を摂食させた対照群ラットについて、1匹あたりの体重増加量および摂餌量を以下の表11に示す。体重増加量は各群5匹の平均値±標準偏差である。
Examination of effects on body weight gain and food intake After iron deficiency anemia, iron-containing feed 1 (ferric citrate), iron-containing feed 2 (heme iron) and iron-containing feed 3 (ferriclysin) Table 11 below shows the weight gain and food intake per animal for each group of rats administered, and for the control group rats fed with iron-containing feed 1 (ferric citrate) from the beginning. . The weight gain is the average value ± standard deviation of 5 animals in each group.
フェリクリシンの水への溶解性の検討
フェリクリシンの溶解性を他の鉄化合物と比較した。鉄化合物としては実施例1で用いた水溶性へム鉄、クエン酸第二鉄及びフェリクリシンを用いた。これらの鉄化合物の各0.1gをそれぞれpH=2およびpH=7の緩衝液1mlに溶解し37℃で90分間保温した。pH=2の緩衝液としてはグリシン-塩酸緩衝液を使用し、pH=7の緩衝液としてはリン酸緩衝液を使用した。各緩衝液中の緩衝剤の濃度は0.1モル/Lとした。各緩衝液を保温後、遠心分離し、沈殿の有無を目視で確認した。また、上清の鉄濃度を原子吸光法により測定した。結果を以下の表12に示す。
Examination of solubility of ferriclysin in water The solubility of ferriclysin was compared with other iron compounds. As the iron compound, the water-soluble heme iron, ferric citrate and ferriclysin used in Example 1 were used. 0.1 g of each of these iron compounds was dissolved in 1 ml of pH = 2 and pH = 7 buffer solutions and incubated at 37 ° C. for 90 minutes. A glycine-hydrochloric acid buffer solution was used as the pH = 2 buffer solution, and a phosphate buffer solution was used as the pH = 7 buffer solution. The concentration of the buffer in each buffer was 0.1 mol / L. Each buffer solution was kept warm and then centrifuged, and the presence or absence of precipitation was visually confirmed. Moreover, the iron concentration of the supernatant was measured by an atomic absorption method. The results are shown in Table 12 below.
フェリクリシンの熱安定性・pH安定性の検討
フェリクリシンは430nmに吸収極大を示すことが知られている。この特徴を利用してフェリクリシンのpHおよび熱安定性を試験した。
上述したようにして米麹抽出液から調製したフェリクリシンを2.5mg/mlとなるように超純水に溶解した。さらに以下の各緩衝液を用いてフェリクリシン濃度が0.25mg/mlとなるように希釈した。pH=2及び3の各緩衝液としてはグリシン-塩酸緩衝液を使用し、pH=4及び5の各緩衝液は酢酸緩衝液を使用し、pH=6及び7の緩衝液としてはリン酸緩衝液を使用し、pH=8の緩衝液としてはトリス-塩酸緩衝液を使用し、pH=9及び10の緩衝液としてはグリシン-水酸化ナトリウム緩衝液を使用した。各緩衝液中の緩衝剤の濃度は0.1モル/Lとした。
各フェリクリシン溶液をネジ付き試験管に入れて試験管を密閉した後、温度120℃、圧力200kPaの条件で 20分間 加圧加熱殺菌した。加熱加圧殺菌の前後で、各溶液の430nmにおける吸光度を測定した。結果を以下の表13に示す。
Examination of heat stability and pH stability of ferricricin It is known that ferricricin exhibits an absorption maximum at 430 nm. This feature was used to test the pH and thermal stability of ferriclysin.
Ferriclicin prepared from the rice bran extract as described above was dissolved in ultrapure water so as to be 2.5 mg / ml. Furthermore, it diluted so that a ferriccrisin density | concentration might be set to 0.25 mg / ml using the following each buffer solution. Glycine-hydrochloric acid buffer is used as each buffer solution at pH = 2 and 3, acetate buffer is used as each buffer solution at pH = 4 and 5, and phosphate buffer is used as a buffer solution at pH = 6 and 7. The tris-hydrochloric acid buffer was used as the pH = 8 buffer, and the glycine-sodium hydroxide buffer was used as the pH = 9 and 10 buffer. The concentration of the buffer in each buffer was 0.1 mol / L.
Each ferriclicin solution was put into a test tube with a screw and the test tube was sealed, and then sterilized by heating under pressure at a temperature of 120 ° C. and a pressure of 200 kPa for 20 minutes. The absorbance at 430 nm of each solution was measured before and after heat and pressure sterilization. The results are shown in Table 13 below.
フェリクリシンの食品成分との反応性の検討
鉄化合物は食品中のさまざまな成分と結合して不溶化される性質を持ち、これが鉄の吸収率を低下させる原因のひとつといわれている。代表的な鉄吸収阻害成分として知られているタンニン酸、及びフィチン酸とフェリクリシンとの反応性を試験し、これらの鉄吸収阻害成分と他の鉄化合物との反応性と比較した。
上述の方法で調製したフェリクリシン、クエン酸第2鉄およびクエン酸第1鉄ナトリウムをそれぞれ鉄として10mg/mlとなるように超純水に溶解した。一方、タンニン酸、及びフィチン酸の0.6%水溶液を作成した。この水溶液のpHを塩酸あるいは水酸化ナトリウムで2.0、4.0、6.0、及び8.0に調整したものをそれぞれ調製した。
上記鉄化合物溶液とタンニン酸水溶液あるいはフィチン酸水溶液とを1:9の体積比で混合し37℃で3時間保温することにより、鉄化合物とこれらの鉄吸収阻害成分とを反応させた。この液を15000rpmで5分間、遠心分離し、その上清を分画分子量10000の膜を用いて限外ろ過した。ろ過液の鉄濃度を原子吸光法で測定した。反応液中の最初の鉄濃度(1mg/ml)に対する、反応後の鉄濃度の割合を%で表示したものを以下の表14に示す。
Examination of the reactivity of ferriclicin with food ingredients <br/> Iron compounds bind to various ingredients in food and become insolubilized, which is said to be one of the causes of decreasing iron absorption . The reactivity of tannic acid, which is known as a typical iron absorption inhibitory component, and phytic acid and ferriclysin was tested and compared with the reactivity of these iron absorption inhibitory components with other iron compounds.
Ferriclysin, ferric citrate and sodium ferrous citrate prepared by the above method were each dissolved in ultrapure water so that the amount of iron was 10 mg / ml. Meanwhile, a 0.6% aqueous solution of tannic acid and phytic acid was prepared. The aqueous solutions were adjusted to pH 2.0, 4.0, 6.0, and 8.0 with hydrochloric acid or sodium hydroxide, respectively.
The iron compound solution and the tannic acid aqueous solution or phytic acid aqueous solution were mixed at a volume ratio of 1: 9 and kept at 37 ° C. for 3 hours to react the iron compound with these iron absorption inhibiting components. This solution was centrifuged at 15000 rpm for 5 minutes, and the supernatant was ultrafiltered using a membrane having a fractional molecular weight of 10,000. The iron concentration of the filtrate was measured by atomic absorption method. Table 14 below shows the ratio of the iron concentration after reaction to the initial iron concentration (1 mg / ml) in the reaction solution expressed in%.
酒類(液体状食品)への配合量の検討
清酒100mlに、フェリクリシンを、それぞれ1mg、5mg、10mg、20mg、50mg、100mg、200mg、500mg、1000mg添加して鉄強化清酒を調製した。得られた鉄強化清酒中のフェリクリシン濃度は、0.01mg/ml、0.05mg/ml、0.1mg/ml、0.2mg/ml、0.5mg/ml、1mg/ml、2mg/ml、5mg/ml、10mg/mlである。
Examination of Compounding Amount in Liquors (Liquid Food) Iron-enriched sake was prepared by adding 1 mg, 5 mg, 10 mg, 20 mg, 50 mg, 100 mg, 200 mg, 500 mg, and 1000 mg of ferriclysin to 100 ml of sake. Ferriclicin concentration in the obtained iron-enriched sake was 0.01 mg / ml, 0.05 mg / ml, 0.1 mg / ml, 0.2 mg / ml, 0.5 mg / ml, 1 mg / ml, 2 mg / ml 5 mg / ml and 10 mg / ml.
各鉄補強清酒について、25人のパネラーにより官能試験を行った。結果を以下の表15に示す。表15中、+++は20人以上のパネラーが美味しいと感じたことを示し、++は7〜19人のパネラーが美味しいと感じたことを示し、+は1〜6人のパネラーが美味しいと感じたことを示し、−は美味しいと感じたパネラーがいなかったことを示す。 Each iron-reinforced sake was subjected to a sensory test by 25 panelists. The results are shown in Table 15 below. In Table 15, ++ indicates that 20 or more panelists felt delicious, ++ indicates that 7 to 19 panelists felt delicious, and + felt that 1 to 6 panelists were delicious. -Indicates that no panelists felt delicious.
菓子(固形状食品)への配合量の検討
クッキー100gに、フェリクリシンを、それぞれ5mg、10mg、20mg、50mg、150mg、300mg、500mg、1000mg、2000mg添加して鉄強化クッキーを調製した。得られた鉄強化クッキー中のフェリクリシン濃度は、0.05mg/g、0.1mg/g、0.2mg/g、0.5mg/g、1.5mg/g、3.0mg/g、5.0mg/g、10mg/g、20mg/gである。
Examination of blending amount into confectionery (solid food) Iron-enriched cookies were prepared by adding 5 mg, 10 mg, 20 mg, 50 mg, 150 mg, 300 mg, 500 mg, 1000 mg and 2000 mg of ferriclysin to 100 g of cookies. The ferriclysin concentration in the obtained iron-enriched cookies was 0.05 mg / g, 0.1 mg / g, 0.2 mg / g, 0.5 mg / g, 1.5 mg / g, 3.0 mg / g, 5 0.0 mg / g, 10 mg / g, 20 mg / g.
各鉄補強クッキーについて、25人のパネラーにより官能試験を行った。結果を以下の表16に示す。表16中、+++は20人以上のパネラーが美味しいと感じたことを示し、++は7〜19人のパネラーが美味しいと感じたことを示し、+は1〜6人のパネラーが美味しいと感じたことを示し、−は美味しいと感じたパネラーがいなかったことを示す。 Each iron reinforced cookie was subjected to a sensory test by 25 panelists. The results are shown in Table 16 below. In Table 16, ++ indicates that 20 or more panelists felt delicious, ++ indicates that 7 to 19 panelists felt delicious, and + felt that 1 to 6 panelists were delicious. -Indicates that no panelists felt delicious.
処方例
以下に、本発明の食品組成物の処方例を示す。
<処方例1 クッキー>
小麦粉(薄力粉)100g、ベーキングパウダー2.5g、食塩1.5g、フェリクリシン200mgを混合し、これにバター40gとミルク50gを加え、これをオーブンで180℃、10分間焼き上げ、鉄強化クッキーを得た。得られたクッキーには、フェリクリシンが1.5mg/g含まれていた。
<処方例2 ゼリー>
ゼラチン5g、ショ糖20g、水50gから膨潤ゼラチンを作る。プレーンヨーグルト140gにフェリクリシン160mgを加え、上記膨潤ゼラチンを加えて冷やす。これを固めて鉄強化ゼリーを得た。得られたゼリーには、フェリクリシンが0.75mg/g含まれていた。
<処方例3 飴>
上白糖500g、水飴440gを少量の水に溶解し、さらにフェリクリシン4gを添加して減圧下130℃で煮詰めた。その後、クエン酸3.5g、酒石酸1.5g、脱脂卵黄蛋白分解物1gを添加した。これを冷却して鉄強化飴を得た。得られた飴には、フェリクリシンが5mg/g含まれていた。
<処方例4 アイスクリーム>
牛乳1200g、生クリーム310g、上白糖300g、脱脂粉乳60g、脱脂卵黄蛋白分解物1g、増粘安定剤6g、フェリクリシン800mgに水を加えて全量2000mlにして溶解した。これを80℃まで加熱した後、ホモミキサーで予備乳化し、引き続きホモゲナイズした。冷却し熟成させた後バニラエッセンス2gを加えフリージングを行った。その後−40℃まで急冷して鉄強化アイスクリームを得た。得られたアイスクリームには、フェリクリシンが0.4mg/g含まれていた。
<処方例5 羊羹>
糸寒天7.5gを溶かし、これに小豆漉し餡660g、グラニュー糖300g、水550ml、フェリクリシン2gを混ぜて溶かして煮詰め、冷やして鉄強化羊羹を得た。得られた羊羹には、フェリクリシンが2mg/g含まれていた。
<処方例6 ヨーグルト>
20%脱脂乳を120℃で、3秒間殺菌した後、ストレプトコッカス・サーモフィルス及びラクトバチルス・カゼイの種菌を培養してヨーグルトベース400gを得た。さらに、砂糖70g、ペクチン3g、フェリクリシン800mgを水に溶解させ、水を加え全量を600gとした。この溶液を120℃で、3秒間殺菌してシロップを得た。上記のヨーグルトベースとシロップを混合し、香料を1g添加した後、均質化して、鉄強化ヨーグルトを得た。得られたヨーグルトには、フェリクリシンが0.8mg/g含まれていた。
<処方例7 牛乳>
牛乳100mlにフェリクリシン40mgを入れてよく撹拌し、鉄強化牛乳を得た。得られた牛乳には、フェリクリシンが0.4mg/ml含まれていた。
<処方例8 チョコレート>
カカオマス25g、カカオバター15g、全脂粉乳15g、粉砂糖30g、粉ミルク15gとフェリクリシン250mgを混和し、45℃で暖めた後に冷却し、鉄強化チョコレートを得た。得られたチョコレートには、フェリクリシンが2.5mg/g含まれていた。
<処方例9 マヨネーズ>
卵黄20gに食塩2.5g、蔗糖1.5g、マスタード1.5g、胡椒0.1g、レモン汁5g、フェリクリシン3.2gを加え、これに酢10gとサラダ油160gとを加えてよく攪拌して鉄強化マヨネーズを得た。得られたマヨネーズには、フェリクリシンが16mg/g含まれていた。
<処方例10 ケチャップ>
トマト1kgを皮をむいてミキサーにかけ、加熱して煮詰めた後、すりおろしたタマネギ10g、ニンニク3gを加え、さらに砂糖10g、塩2g、フェリクリシン4.8gを加える。弱火にして香辛料(シナモンスティック、クローブ、胡椒、唐辛子)1g、酢を30g加え、一度加熱した後、冷まして鉄強化ケチャップを得た。得られたケチャップには、フェリクリシンが16mg/g含まれていた。
<処方例11 カレールウ>
小麦粉(薄力粉)125g、バター100g、カレー粉20gとフェリクリシン1.0gに、少量の水を加えて混和し、固めて鉄強化カレールウを得た。得られたカレールウには、フェリクリシンが4mg/g含まれていた。
<処方例12 蒲鉾>
魚のすり身100g、粉末マッシュポテト10g、小麦粉5g、卵白50g、塩2g、砂糖0.2g、みりん10g、フェリクリシン1.3gを加え、これらを混ぜてペースト状にし、蒸し器で蒸して鉄強化蒲鉾を得た。得られた蒲鉾には、フェリクリシンが7mg/g含まれていた。
<処方例13 佃煮>
戻した昆布25g、かつおだし150ml、砂糖15g、醤油15g、酢10g、フェリクリシン400mgを混合し、沸騰させてから中火で煮詰めて鉄強化佃煮を得た。得られた佃煮には、フェリクリシンが5mg/g含まれていた。
<処方例14 ふりかけ>
いりごま15g、味付けごま20g、味付け削り節10g、味付けかつお塩顆粒10g、味付けのり顆粒10g、フェリクリシン1.6gをよく混合して、鉄強化ふりかけを得た。得られたふりかけには、フェリクリシンが25mg/g含まれていた。
<処方例15 米飯>
白米150g、水220gとフェリクリシン160mgを混合し、炊飯器で炊き上げ、鉄強化米飯を得た。得られた米飯には、フェリクリシンが0.5mg/g含まれていた。
<処方例16 うどん麺>
水400g、塩50gを混合して塩を溶かし、これに小麦粉(中力粉)1000g、フェリクリシン1.6gを混ぜ、よくこねた。固まったらこれをよく伸ばし、5mm幅に切った。これを10分茹でて、その後冷やして鉄強化うどん麺を得た。得られたうどん麺にはフェリクリシンが3mg/g含まれていた。
<処方例17 清酒>
清酒100mlにフェリクリシン20mgを加え、よく撹拌して鉄強化清酒を得た。得られた清酒には、フェリクリシンが0.2mg/ml含まれていた。
<処方例18 焼酎>
焼酎100mlにフェリクリシン40mgを加え、よく撹拌して鉄強化焼酎を得た。得られた焼酎には、フェリクリシンが0.4mg/ml含まれていた。
<処方例19 ワイン>
ワイン100mlにフェリクリシン20mgを加え、よく撹拌して鉄強化ワインを得た。得られたワインには、フェリクリシンが0.2mg/ml含まれていた。
<処方例20 ビール>
ビール100mlにフェリクリシン12mgを加え、撹拌して鉄強化ビールを得た。得られたビールには、フェリクリシンが0.12mg/ml含まれていた。
<処方例21 ウィスキー>
ウィスキー100mlにフェリクリシン100mgを加え、よく撹拌して鉄強化ウィスキーを得た。得られたウィスキーには、フェリクリシンが1mg/ml含まれていた。
<処方例22 ブランデー>
ブランデー100mlにフェリクリシン100mgを加え、よく撹拌して鉄強化ブランデーを得た。得られたブランデーには、フェリクリシンが1mg/ml含まれていた。
<処方例23 スピリッツ>
スピリッツ100mlにフェリクリシン100mgを加え、よく撹拌して鉄強化スピリッツを得た。得られたスピリッツには、フェリクリシンが1mg/ml含まれていた。
<処方例24 リキュール>
リキュ−ル100mlにフェリクリシン100mgを加え、よく撹拌して鉄強化リキュールを得た。得られたリキュールには、フェリクリシンが1mg/ml含まれていた。
<処方例25 みりん>
みりん100mlにフェリクリシン400mgを加え、よく撹拌して鉄強化みりんを得た。得られたみりんには、フェリクリシンが4mg/ml含まれていた。
<処方例26 茶>
お茶100mlにフェリクリシン40mgを加え、よく撹拌して鉄強化茶を得た。得られた茶には、フェリクリシンが0.4mg/ml含まれていた。
<処方例27 コーヒー>
コーヒー100mlにフェリクリシン40mgを加え、よく撹拌して鉄強化コーヒーを得た。得られたコーヒーには、フェリクリシンが0.4mg/ml含まれていた。
<処方例28 スポーツドリンク>
水100ml、果糖5g、ショ糖2g、クエン酸0.3g、ナトリウム20mg、カルシウム2mg、カリウム20mg、アルギニン20mg、イソロイシン10mg、バリン10mg、ロイシン10mg、ビタミンC100mg、β−カロチン1mgにフェリクリシン15mgを加え、よく撹拌して鉄強化スポーツドリンクを得た。得られたスポーツドリンクには、フェリクリシンが0.15mg/ml含まれていた。
<処方例29 清涼飲料水>
バレンシアオレンジ果汁30ml、レモン果汁3ml、果糖1.5g、クエン酸0.5g、ビタミンC0.1gにフェリクリシン15mgを加え、これに水を加えて100mlとし、よく撹拌した後に炭酸ガスを封入し、鉄強化清涼飲料水を得た。得られた清涼飲料水には、フェリクリシンが0.15mg/ml含まれていた。
<処方例30 スープ>
ポタージュスープ100mlにフェリクリシン40mgを加え、よく撹拌して鉄強化スープを得た。得られたスープには、フェリクリシンが0.4mg/ml含まれていた。
Formulation Examples Formulation examples of the food composition of the present invention are shown below.
<Prescription Example 1 Cookie>
Mix 100g of wheat flour (weak flour), 2.5g baking powder, 1.5g salt, 200mg ferriccricin, add 40g butter and 50g milk, and bake this in an oven at 180 ° C for 10 minutes to obtain an iron fortified cookie. It was. The obtained cookie contained 1.5 mg / g of ferriclysin.
<Prescription Example 2 Jelly>
Swelled gelatin is made from 5 g of gelatin, 20 g of sucrose, and 50 g of water. Add 160 mg of ferriclysin to 140 g of plain yogurt, add the above swollen gelatin and cool. This was hardened to obtain an iron-reinforced jelly. The obtained jelly contained 0.75 mg / g of ferriclysin.
<Prescription Example 3>
500 g of upper white sugar and 440 g of starch syrup were dissolved in a small amount of water, and 4 g of ferriclysin was further added and boiled at 130 ° C. under reduced pressure. Thereafter, 3.5 g of citric acid, 1.5 g of tartaric acid, and 1 g of defatted egg yolk protein degradation product were added. This was cooled to obtain an iron reinforced iron. The obtained sputum contained 5 mg / g of ferriclysin.
<Prescription Example 4 Ice Cream>
A total amount of 2000 ml was dissolved by adding water to 1200 g of milk, 310 g of fresh cream, 300 g of super white sugar, 60 g of skim milk powder, 1 g of defatted egg yolk proteolysate, 6 g of thickening stabilizer and 800 mg of ferriclysin. This was heated to 80 ° C., pre-emulsified with a homomixer, and then homogenized. After cooling and aging, 2 g of vanilla essence was added and freezing was performed. Thereafter, it was rapidly cooled to −40 ° C. to obtain an iron-reinforced ice cream. The obtained ice cream contained 0.4 mg / g of felicricin.
<Prescription Example 5 Yokan>
7.5 g of thread agar was dissolved, 660 g of red bean paste, 300 g of granulated sugar, 550 ml of water and 2 g of ferriclysin were mixed and dissolved, boiled and cooled to obtain an iron-enriched sheep. The resulting sheep had 2 mg / g of ferriclysin.
<Prescription Example 6 Yogurt>
After sterilizing 20% skim milk at 120 ° C. for 3 seconds, 400 g of yogurt base was obtained by culturing Streptococcus thermophilus and Lactobacillus casei inoculum. Furthermore, 70 g of sugar, 3 g of pectin, and 800 mg of ferriclysin were dissolved in water, and water was added to make the total amount 600 g. This solution was sterilized at 120 ° C. for 3 seconds to obtain a syrup. The above yogurt base and syrup were mixed, 1 g of flavor was added, and then homogenized to obtain iron-fortified yogurt. The resulting yogurt contained 0.8 mg / g of ferriclysin.
<Prescription Example 7 Milk>
40 mg of ferriclysin was added to 100 ml of milk and stirred well to obtain iron-enriched milk. The obtained milk contained 0.4 mg / ml of ferriclysin.
<Prescription Example 8 Chocolate>
25 g of cacao mass, 15 g of cacao butter, 15 g of whole fat powdered milk, 30 g of powdered sugar, 15 g of powdered milk and 250 mg of ferriclysin were mixed, heated at 45 ° C. and then cooled to obtain iron-reinforced chocolate. The obtained chocolate contained 2.5 mg / g of ferriclysin.
<Prescription Example 9 Mayonnaise>
Add 2.5 g of salt, 1.5 g of sucrose, 1.5 g of mustard, 0.1 g of pepper, 5 g of lemon juice, 3.2 g of ferriccricin to 20 g of egg yolk, add 10 g of vinegar and 160 g of salad oil and stir well. Obtained iron-reinforced mayonnaise. The obtained mayonnaise contained 16 mg / g of felicricin.
<Prescription Example 10 Ketchup>
Peel 1 kg of tomatoes into a mixer, heat and boil, then add 10 g of grated onion and 3 g of garlic, then add 10 g of sugar, 2 g of salt and 4.8 g of ferriclysin. Slowly heat, add 1 g of spices (cinnamon sticks, cloves, pepper, pepper) and 30 g of vinegar, heat once, cool and obtain iron-reinforced ketchup. The obtained ketchup contained 16 mg / g of felicricin.
<Prescription Example 11 Carreau>
A small amount of water was added to and mixed with 125 g of wheat flour (weak flour), 100 g of butter, 20 g of curry powder and 1.0 g of ferricricin, and solidified to obtain iron-reinforced curry roux. The resulting curry roux contained 4 mg / g of ferriclysin.
<Prescription Example 12>
Add fish surimi 100g, powdered mashed potato 10g, wheat flour 5g, egg white 50g, salt 2g, sugar 0.2g, mirin 10g, ferriclysin 1.3g, mix these into a paste, steam in a steamer to obtain an iron-enriched rice cake It was. The obtained koji contained 7 mg / g of ferriclysin.
<Prescription example 13
25 g of returned kelp, 150 ml of bonito dashi, 15 g of sugar, 15 g of soy sauce, 10 g of vinegar and 400 mg of ferriclysin were mixed and boiled, then boiled on medium heat to obtain an iron-enriched boiled simmered boiled fish. The obtained boiled koji contained 5 mg / g of felicricin.
<Prescription Example 14 Sprinkle>
15 g of sesame seeds, 20 g of seasoned sesame seeds, 10 g of seasoned shavings, 10 g of seasoned bonito salt granules, 10 g of seasoned glue grains, and 1.6 g of ferriclysin were mixed well to obtain an iron-reinforced sprinkle. The obtained sprinkle contained 25 mg / g of ferriclysin.
<Prescription Example 15 Rice>
150 g of white rice, 220 g of water, and 160 mg of felicricin were mixed and cooked in a rice cooker to obtain iron-reinforced rice. The obtained cooked rice contained 0.5 mg / g of felicricin.
<Prescription Example 16 Udon noodles>
400 g of water and 50 g of salt were mixed to dissolve the salt, and 1000 g of flour (medium flour) and 1.6 g of ferriclysin were mixed and kneaded well. When solidified, this was stretched well and cut into 5 mm widths. This was boiled for 10 minutes and then cooled to obtain iron-enhanced udon noodles. The obtained udon noodles contained 3 mg / g of felicricin.
<Prescription Example 17 Sake>
To 100 ml of sake, 20 mg of ferriclysin was added and stirred well to obtain iron-enriched sake. The obtained sake contained 0.2 mg / ml of ferriclysin.
<Prescription Example 18 Shochu>
To 100 ml of shochu, 40 mg of ferriclysin was added and stirred well to obtain iron-enriched shochu. The obtained shochu contained 0.4 mg / ml of ferriclysin.
<Prescription Example 19 Wine>
20 mg of ferriclysin was added to 100 ml of wine and stirred well to obtain an iron-enriched wine. The obtained wine contained 0.2 mg / ml of ferriclysin.
<Prescription Example 20 Beer>
12 mg of ferriclysin was added to 100 ml of beer and stirred to obtain an iron-reinforced beer. The obtained beer contained 0.12 mg / ml of ferriclysin.
<Prescription Example 21 Whiskey>
100 mg of ferriccricin was added to 100 ml of whiskey and stirred well to obtain an iron-reinforced whiskey. The obtained whiskey contained 1 mg / ml of ferriclysin.
<Prescription Example 22 Brandy>
100 mg of brandy was added with 100 mg of ferriclysin and stirred well to obtain an iron-strengthened brandy. The resulting brandy contained 1 mg / ml of ferriclysin.
<Prescription Example 23 Spirits>
100 mg of ferriclysin was added to 100 ml of spirits and stirred well to obtain iron-enriched spirits. The resulting spirit contained 1 mg / ml of ferriclysin.
<Prescription Example 24 Liqueur>
To 100 ml of liqueur, 100 mg of ferriclysin was added and stirred well to obtain an iron-enhanced liqueur. The obtained liqueur contained 1 mg / ml of ferriclysin.
<Prescription Example 25 Mirin>
To 100 ml of mirin, 400 mg of ferriclysin was added and stirred well to obtain iron-enriched mirin. The obtained mirin contained 4 mg / ml of ferriclysin.
<Prescription Example 26 Tea>
40 mg of ferriclysin was added to 100 ml of tea and stirred well to obtain iron-enhanced tea. The obtained tea contained 0.4 mg / ml of ferriclysin.
<Prescription Example 27 Coffee>
40 mg of ferriclysin was added to 100 ml of coffee, and stirred well to obtain iron-reinforced coffee. The obtained coffee contained 0.4 mg / ml of ferriclysin.
<Prescription Example 28 Sports Drink>
100 ml of water, 5 g of fructose, 2 g of sucrose, 0.3 g of citric acid, 20 mg of sodium, 2 mg of calcium, 20 mg of potassium, 20 mg of arginine, 10 mg of isoleucine, 10 mg of valine, 10 mg of leucine, 100 mg of vitamin C, 1 mg of β-carotene and 15 mg of ferriclysin Stir well and get an iron-enhanced sports drink. The obtained sports drink contained 0.15 mg / ml of ferriclysin.
<Prescription Example 29 Soft Drinks>
15 ml of Valencia orange juice, 3 ml of lemon juice, 1.5 g of fructose, 0.5 g of citric acid, 0.1 g of vitamin C, 15 mg of ferriclysin are added to this to make 100 ml, and after stirring well, carbon dioxide gas is enclosed. An iron-reinforced soft drink was obtained. The resulting soft drink contained 0.15 mg / ml of felicricin.
<Prescription Example 30 Soup>
40 mg of ferriclysin was added to 100 ml of potage soup and stirred well to obtain an iron-enriched soup. The resulting soup contained 0.4 mg / ml of ferriclysin.
本発明の鉄補給剤は、鉄欠乏性貧血を始めとする鉄欠乏による症状の予防、改善又は治療のために好適に使用できる。また、本発明の食品添加剤は、鉄補給のため、又は鉄欠乏性貧血の予防又は改善のための機能性食品、又は特定保健用食品への添加剤として好適に使用できる。
The iron supplement of the present invention can be suitably used for the prevention, amelioration or treatment of symptoms due to iron deficiency including iron deficiency anemia. Moreover, the food additive of the present invention can be suitably used as an additive to functional foods for iron supplementation or prevention or improvement of iron deficiency anemia, or foods for specified health use.
Claims (20)
(i) 鉄を補給する作用を有することを特徴とし、鉄を補給するために用いられる旨の表示を付した食品組成物
(ii) 鉄を補助する作用を有することを特徴とし、鉄を補助するために用いられる旨の表示を付した食品組成物
(iii) 鉄を強化する作用を有することを特徴とし、鉄を強化するために用いられる旨の表示を付した食品組成物
(iv) 鉄を付加する作用を有することを特徴とし、鉄を付加するために用いられる旨の表示を付した食品組成物
(v) 体内の鉄含量を正常に保つ作用を有することを特徴とし、体内の鉄含量を正常に保つために用いられる旨の表示を付した食品組成物
(vi) 体内の鉄不足を解消又は軽減する作用を有することを特徴とし、体内の鉄不足を解消又は軽減するために用いられる旨の表示を付した食品組成物
The food composition according to any one of the following (i) to (vi), comprising a siderophore and trivalent iron ions.
(i) A food composition characterized by having an action of replenishing iron and labeled as being used to replenish iron
(ii) A food composition characterized by having an effect of assisting iron and labeled to indicate that it is used to supplement iron
(iii) A food composition characterized by having an effect of strengthening iron and labeled to indicate that it is used to strengthen iron
(iv) A food composition characterized by having an action of adding iron and having a label indicating that it is used for adding iron
(v) A food composition characterized by having a function of maintaining the normal iron content in the body and labeled as being used to maintain the normal iron content in the body
(vi) A food composition characterized by having an action of eliminating or reducing iron deficiency in the body and labeled to indicate that it is used to eliminate or reduce iron deficiency in the body
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Cited By (9)
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JP2007091711A (en) * | 2005-09-02 | 2007-04-12 | Gekkeikan Sake Co Ltd | Preventing or improving agent of fatigue |
JP2008054579A (en) * | 2006-08-31 | 2008-03-13 | Gekkeikan Sake Co Ltd | Method for producing biological product whose production is suppressed by iron |
JP2008201677A (en) * | 2007-02-16 | 2008-09-04 | Gekkeikan Sake Co Ltd | Anti-inflammatory agent and antioxidant |
JP2008303168A (en) * | 2007-06-07 | 2008-12-18 | Japan Health Science Foundation | Osteoclast-controlling agent and method for screening the same |
JP2012162566A (en) * | 2012-05-18 | 2012-08-30 | Gekkeikan Sake Co Ltd | Anti-inflammatory agent and antioxidant |
KR20140027196A (en) * | 2011-03-29 | 2014-03-06 | 비포르 (인터내셔날) 아게 | Fe(iii) complexes for the treatment and prophylaxis of iron deficiency symptoms and iron deficiency anaemias |
JP2018507260A (en) * | 2015-03-04 | 2018-03-15 | ケリク バイオファーマシューティカルス, インコーポレーテッド | Use of ferric citrate in the treatment of iron deficiency anemia |
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Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3342795A (en) * | 1962-03-02 | 1967-09-19 | Ciba Geigy Corp | Ferrichrysin, desferrichrysin, and derivatives thereof |
-
2005
- 2005-01-13 JP JP2005006829A patent/JP4931352B2/en not_active Expired - Fee Related
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3342795A (en) * | 1962-03-02 | 1967-09-19 | Ciba Geigy Corp | Ferrichrysin, desferrichrysin, and derivatives thereof |
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JP2007091711A (en) * | 2005-09-02 | 2007-04-12 | Gekkeikan Sake Co Ltd | Preventing or improving agent of fatigue |
JP2008054579A (en) * | 2006-08-31 | 2008-03-13 | Gekkeikan Sake Co Ltd | Method for producing biological product whose production is suppressed by iron |
JP2008201677A (en) * | 2007-02-16 | 2008-09-04 | Gekkeikan Sake Co Ltd | Anti-inflammatory agent and antioxidant |
JP2008303168A (en) * | 2007-06-07 | 2008-12-18 | Japan Health Science Foundation | Osteoclast-controlling agent and method for screening the same |
JP2014509624A (en) * | 2011-03-29 | 2014-04-21 | ヴィフォール (インターナショナル) アクチェンゲゼルシャフト | Iron (III) complex compounds for the treatment and prevention of iron deficiency symptoms and iron deficiency anemia |
KR20140027196A (en) * | 2011-03-29 | 2014-03-06 | 비포르 (인터내셔날) 아게 | Fe(iii) complexes for the treatment and prophylaxis of iron deficiency symptoms and iron deficiency anaemias |
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JP2012162566A (en) * | 2012-05-18 | 2012-08-30 | Gekkeikan Sake Co Ltd | Anti-inflammatory agent and antioxidant |
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