JP5345751B2 - Preventive or ameliorating agent for anemia for domestic animals - Google Patents
Preventive or ameliorating agent for anemia for domestic animals Download PDFInfo
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本発明はダイフラクトースアンハイドライドIII (以下、DFAIII ということもある)及び/又はダイフラクトースアンハイドライドIV(以下、DFAIVということもある)を有効成分として含有する家畜動物用貧血予防剤又は改善剤に関するものである。 The present invention relates to a preventive or ameliorating agent for livestock animals containing difructose anhydride III (hereinafter sometimes referred to as DFAIII) and / or difructose anhydride IV (hereinafter also referred to as DFAIV) as an active ingredient. Is.
新生子畜は貧血が発生しやすく、子畜の貧血はミネラル不足による機能障害の代表的な例の一つに挙げられている。出生直後の新生子畜は体温を一定に保持することが困難なため、造血機能を昂進する鉄の機能が重要となる。鉄はヘモグロビンの構成成分として造血機能の改善に重要な働きをする。新生子畜が体温の恒常性を維持できなくなると、有害微生物が子畜体内に侵入しやすくなり、下痢、肺炎等の発生により子畜の生存率が低下することが知られている。 Newborn pups are prone to anemia, and anemia of pups is listed as one of the typical examples of dysfunction caused by mineral deficiency. Since the newborn pups just after birth are difficult to maintain a constant body temperature, the function of iron that promotes the hematopoietic function is important. Iron plays an important role in improving the hematopoietic function as a component of hemoglobin. It is known that when newborn pups cannot maintain the homeostasis of body temperature, harmful microorganisms easily enter the pups and the survival rate of the pups decreases due to the occurrence of diarrhea, pneumonia and the like.
黒毛和種子牛の消耗性疾患多発農家における発病状況を調べた報告では、59日齢以内の健康と思われる子牛に貧血がみられ、特に30〜59日齢で血清中の鉄濃度が低下していた。病気はこの時期に多発していることから、これは貧血による抗病力の低下が要因と考えられている。 According to a report on the occurrence of debilitating diseases of Japanese black cattle cattle, anemia was observed in calves that seemed to be healthy within 59 days of age, and the serum iron concentration decreased especially at 30-59 days of age. Was. Since the disease occurs frequently at this time, this is considered to be caused by a decrease in anti-disease due to anemia.
近年、受精卵移植技術の実用化に伴い、双子生産は牛肉資源の拡大策として大きな期待が持たれている。しかし、双子牛は出生後の生存率が低く、その原因の一つとして、双子牛の貧血発生率が高いことが影響していると報告されている。双子牛が単子牛より、初産牛から生まれた子牛が経産牛から生まれた子牛より、また雄子牛が雌子牛よりも、出生直後に造血機能の低下が認められている。 In recent years, with the practical application of fertilized egg transplantation technology, twin production has great expectations as a measure for expanding beef resources. However, it is reported that twin cattle have a low survival rate after birth, and one of the causes is that twin cattle have a high incidence of anemia. Decreased hematopoietic function has been observed immediately after birth, with twin calves being more than single calves, calves born from first calves more than calves born from heifers, and calves more than female calves.
新生子豚では、子豚が初乳の吸飲を開始すると、吸収された初乳の成分が血液中に入り、循環血漿量が増加するため、血液が希釈されて貧血が生じることが知られている。哺育期子豚の発育速度は他の幼齢動物に比べてきわめて早く、循環血漿量の急激な増加に対応して血液中の赤血球数やヘモグロビン(血色素)量を正常な水準に維持するために、多量の鉄分が必要とされる。しかし、母豚は閉鎖的な舎飼い方式で飼育されており、本来、土や草などから摂取していた鉄をはじめとする微量要素が不足気味となり、乳汁中の鉄分が少なくなるため、哺乳子豚は貧血を発生しやすい状況にある。 In newborn piglets, it is known that when the piglet starts sucking colostrum, the components of the absorbed colostrum enter the blood and the circulating plasma volume increases, resulting in blood dilution and anemia. ing. The growth rate of suckling piglets is very fast compared to other young animals, so that the number of red blood cells and hemoglobin (hemoglobin) in the blood can be maintained at normal levels in response to the rapid increase in circulating plasma volume. A large amount of iron is required. However, mother pigs are kept in a closed house-keeping system, and trace elements such as iron that were originally ingested from soil and grass are scarce, and the amount of iron in milk is reduced. Piglets are prone to anemia.
このように、新生子牛や新生子豚の貧血はミネラル不足による機能障害の代表的なものの一つであり、貧血状態で生まれた子牛や子豚はその後の生存率や成長速度が低下し、更に、造血機能の低下は新生子畜の免疫機能にも悪影響を及ぼす。 In this way, anemia in newborn calves and newborn piglets is one of the typical dysfunctions due to mineral deficiencies, and calves and piglets born in anemia have a lower survival rate and subsequent growth rate. Furthermore, the decrease in hematopoietic function also adversely affects the immune function of newborn pups.
現在、新生子牛や新生子豚の造血機能の改善方法としては、鉄剤の投与が推奨されている。しかし、過剰に投与された鉄は消化管における有害微生物の増殖や過酸化促進作用による組織の損傷などの悪影響を及ぼすため、新生子畜における造血機能の改善とともに鉄の有害作用防止にも効果的な方法を開発することが求められている。 Currently, the administration of iron is recommended as a method for improving the hematopoietic function of newborn calves and newborn piglets. However, excessive administration of iron adversely affects the growth of harmful microorganisms in the gastrointestinal tract and tissue damage due to the promotion of peroxidation. To develop a new method.
例えば特許文献1には、新生子牛に対してラクトフェリンと鉄を投与することにより、新生子牛の造血機能の改善及び貧血の予防に早期の著効が得られる上、投与直後における血漿中鉄含量の急激な上昇を抑えて、毒性等の副作用を緩和することが記載されている。しかし、ラクトフェリン単独では造血機能の改善及び貧血の予防効果が発揮されず、ラクトフェリンと鉄剤を併用することが必要であるため、この手法では鉄剤の投与に起因する消化組織に対する副作用の恐れは解消されない。また、ラクトフェリンは水分、熱、酸、酵素などに弱く、そのままの状態で摂取した場合には胃の中で分解されてしまうため、広いpH域で長期間安定であり、耐熱性を有するような加工が必要とされている(例えば、特許文献2を参照)。 For example, Patent Document 1 discloses that by administering lactoferrin and iron to a newborn calf, early improvement can be obtained in improving the hematopoietic function and preventing anemia of the newborn calf, and plasma iron immediately after administration. It describes that side effects such as toxicity are alleviated by suppressing a rapid increase in content. However, lactoferrin alone does not improve the hematopoietic function and prevent anemia, and it is necessary to use lactoferrin and iron together, so this technique does not eliminate the risk of side effects on digestive tissues caused by iron administration . In addition, lactoferrin is vulnerable to moisture, heat, acid, enzymes, etc., and will be decomposed in the stomach if taken as it is, so it is stable over a wide pH range for a long time and has heat resistance. Processing is required (see, for example, Patent Document 2).
また、ペプチド鉄には子豚の貧血を改善する効果があるという報告があり(例えば、非特許文献1を参照)、国内外で飼料添加物として広く用いられている。ペプチド化されたミネラルは、小腸内のペプチド吸収部位からそのまま体内に吸収されると考えられており、無機ミネラルと比べ、吸収利用性の良さ、体外への排泄の少なさ、安定性の良さなどの特徴を有している。しかし、ミネラル栄養はバランスが重要であり、過剰は欠乏と同じように悪影響を及ぼすため、欠乏を解消するのに、必要量以上に添加することは望ましくないことも指摘されている。 Moreover, there is a report that peptide iron has an effect of improving anemia of piglets (see, for example, Non-Patent Document 1), and it is widely used as a feed additive at home and abroad. Peptidized minerals are thought to be absorbed directly into the body from the peptide absorption site in the small intestine. Compared to inorganic minerals, it has better absorbability, less excretion outside the body, better stability, etc. It has the characteristics. However, it has also been pointed out that it is not desirable to add more than necessary to eliminate deficiency, since the balance of mineral nutrition is important and excess is as bad as deficiency.
一方、フラクトース2分子が結合してなるオリゴ糖であるDFAIII 及びDFAIVについては、DFAIII 及び/又はDFAIVが、家畜動物のカルシウム欠乏症や浮腫の予防や治療に効果を有することが既に開示されている(例えば、特許文献3を参照)。しかしながら、鉄吸収を促進し、貧血の予防や改善に効果を有することは記載されていない。
本発明は、このような技術の現状に鑑み、より効率的に鉄吸収を促進し、造血機能を高め、貧血状態を改善することのできる、安全性の高い家畜動物用貧血予防剤又は改善剤、及びこれを含有する飼料を開発することを目的になされたものである。 In view of the present state of the art, the present invention is a highly safe anemia-preventing agent or ameliorating agent for livestock animals that can more efficiently promote iron absorption, enhance hematopoietic function, and improve anemia. And the purpose of developing a feed containing the same.
本発明は、上記課題を解決するためになされたものであって、本発明者らは、新生子牛や新生子豚といった新生子畜の鉄の吸収促進作用及び貧血改善作用を有する天然物由来の素材について、多方面から鋭意研究を進めた結果、イヌリンに由来するオリゴ糖であるDFAIII 、及びレバンに由来するオリゴ糖であるDFAIVが新生子畜の鉄の吸収促進及び貧血改善に著効を示すことを見出し、本発明を完成するに至った。 The present invention has been made in order to solve the above-mentioned problems, and the present inventors have derived from natural products having an effect of promoting iron absorption and improving anemia of newborn dairy animals such as newborn calves and newborn piglets. As a result of diligent research on these materials, DFAIII, an oligosaccharide derived from inulin, and DFAIV, an oligosaccharide derived from levan, have a significant effect on promoting iron absorption and improving anemia in newborns. As a result, the present invention has been completed.
すなわち、本発明は、DFAIII 及び/又はDFAIVを有効成分とする家畜動物用貧血予防剤又は改善剤に関するものであり、また、家畜動物用飼料に関するものである。 That is, the present invention relates to a preventive or ameliorating agent for livestock animals containing DFAIII and / or DFAIV as an active ingredient, and also relates to a feed for livestock animals.
本発明において有効成分として使用するDFAIII (difructose anhydride III )は、フラクトース2分子が1,2’及び2,3’で結合している2糖類(di−D−fructofranose−1,2’:2,3’dianhydride)である。また、有効成分として使用するDFAIV(difructose anhydride IV)は、フラクトース2分子が2,6’及び6,2’で結合している2糖類(di−D−fructofranose−2,6’:6,2’dianhydride)である。なお、有効成分としては、DFAIII 及び/又はDFAIVの精製品、粗精製品、製造工程において生成する中間生成物、同排液、これらの処理物(濃縮物、ペースト化物、乾燥物、希釈物、懸濁物、乳化物の少なくともひとつ)から選ばれる少なくともひとつが包含される。 DFAIII (difructose anhydride III) used as an active ingredient in the present invention is a disaccharide in which two molecules of fructose are linked by 1, 2 'and 2, 3' (di-D-fructofuranose-1, 2 ': 2, 3 'dianhydride). In addition, DFA IV (difructose anhydride IV) used as an active ingredient is a disaccharide (di-D-fructofranose-2, 6 ′: 6, 2) in which two molecules of fructose are bound at 2, 6 ′ and 6, 2 ′. 'dianhydride). In addition, as an active ingredient, DFAIII and / or DFAIV refined product, crude refined product, intermediate product produced in the production process, the same effluent, these processed products (concentrate, pasted product, dried product, diluted product, At least one selected from suspensions and emulsions is included.
本発明においては有効成分としてDFAIII 及び/又はDFAIVを使用するが、所望に応じて、クエン酸鉄、コハク酸クエン酸鉄ナトリウム、DL−トレオニン鉄、フマル酸第一鉄、硫酸鉄(乾燥)、ペプチド鉄といった飼料添加物として認められている鉄剤を併用することができる。その投与量は、他のミネラルとのバランスを考慮し、過剰にならない範囲で極力少ない量が望ましいが、格別の限定はない。 In the present invention, DFAIII and / or DFAIV is used as an active ingredient, and if desired, iron citrate, sodium iron succinate, DL-threonine iron, ferrous fumarate, iron sulfate (dried), An iron agent recognized as a feed additive such as peptide iron can be used in combination. In consideration of the balance with other minerals, the dose is preferably as small as possible within a range that does not become excessive, but there is no particular limitation.
本発明にしたがって、上記した有効成分を用いて家畜動物用貧血予防剤又は改善剤、及びこれを含有する飼料を調製するが、その際、DFAIII 及び、あるいはDFAIVの投与量は、1日あたり、動物の体重1kgにつき0.01〜2.0g、好ましくは0.05〜0.5gの範囲で投与するのがよい。 According to the present invention, an anemia-preventing or ameliorating agent for livestock animals and a feed containing the same are prepared using the above-mentioned active ingredients, and the dosage of DFAIII and / or DFAIV is as follows: The dose is 0.01 to 2.0 g, preferably 0.05 to 0.5 g per kg of the animal body weight.
また、その投与形態は、そのまま投与してもよく、あるいは、初乳、生乳、代用乳及び人工乳に添加して投与してもよい。 Moreover, the administration form may be administered as it is, or it may be added to colostrum, raw milk, milk substitute or artificial milk for administration.
本発明の貧血予防剤又は改善剤、及びこれを含有する飼料は、牛、豚のほか、水牛、羊、山羊、馬、犬、猫等といった各種の家畜に対して適用することができる。 The anemia preventive or ameliorating agent of the present invention and feed containing the same can be applied to various livestock such as buffalo, sheep, goats, horses, dogs, cats, etc. in addition to cattle and pigs.
本発明によれば、新生子牛や新生子豚といった新生子畜の貧血を改善し、死亡率を低減させるとともに、その後の発育を高め、畜産経営に多大な貢献をもたらすものである。 According to the present invention, it is possible to improve anemia of newborn kittens such as newborn calves and newborn piglets, to reduce the mortality rate, to enhance subsequent growth, and to make a great contribution to livestock management.
以下に本発明の実施例を示すが、本発明は以下の実施例に何ら限定されるものではない。 Examples of the present invention are shown below, but the present invention is not limited to the following examples.
ホルスタイン種の新生子牛18頭を、対照区、DFAIII 区、およびDFAIV区の3群に各6頭ずつ分けた。生後7日間初乳を給与した後、対照区には市販の代用乳15%溶液2Lを与え、DFAIII 区とDFAIV区には、前記代用乳にそれぞれDFAIII またはDFAIVの5%溶液100mlを混合して与えた。代用乳はそれぞれ1日あたり2回、生後4週齢まで給与し、市販の哺乳子牛用飼料および水は自由に摂取させた。生後4週齢時に子牛の頸静脈より採血し、血清鉄濃度および血液中のヘマトクリット値とヘモグロビン濃度を測定した。血清鉄はフェロジン比色法で測定し、血液中のヘマトクリット値とヘモグロビン濃度はQBCVオートリード(アイデックスラボラトリー株式会社)で測定した。結果を表1に示した。 Eighteen newborn Holstein calves were divided into three groups of 6 groups, a control group, a DFAIII group, and a DFAIV group. After feeding colostrum for 7 days after birth, the control group is given 2 L of a commercially available 15% milk substitute solution, and the DFA III and DFA IV groups are mixed with 100 ml of a 5% solution of DFA III or DFA IV, respectively. Gave. Milk replacers were fed twice a day, up to 4 weeks of age, and commercially available calf feed and water were freely consumed. At the age of 4 weeks of age, blood was collected from the jugular vein of calves, and the serum iron concentration, hematocrit value and hemoglobin concentration in the blood were measured. Serum iron was measured by a ferrozine colorimetric method, and hematocrit value and hemoglobin concentration in blood were measured by QBCV Autoread (IDEX Laboratory Co., Ltd.). The results are shown in Table 1.
DFAIII およびDFAIVを投与したホルスタイン種の子牛は、投与しなかった子牛と比較し、血清鉄濃度、ヘマトクリット値およびヘモグロビン濃度が高まり、造血機能が改善された。 Holstein calves to which DFAIII and DFAIV were administered had higher serum iron levels, hematocrit values and hemoglobin levels and improved hematopoietic function compared to calves that had not been administered.
新生子豚6腹54頭を、対照区、DFAIII 区、およびDFAIV区の3群に、各2腹18頭ずつ分けた。子豚は母豚と同居させ、市販の哺乳子豚用飼料および水は自由に摂取させた。DFAIII 区とDFAIV区では、それぞれDFAIII またはDFAIVの5%溶液20mlを1日1回、生後5日齢まで強制経口投与した。調査項目は生後24日齢までの生存率(%)とした。結果を図1に示した。 Sixty six newborn piglets were divided into three groups, a control group, a DFAIII group, and a DFAIV group. The piglets were allowed to live with the mother pigs, and commercially available feed and water for suckling piglets were freely consumed. In DFAIII and DFAIV groups, 20 ml of a 5% solution of DFAIII or DFAIV was orally administered by gavage once a day until 5 days of age. The survey item was survival rate (%) up to 24 days of age. The results are shown in FIG.
DFAIII およびDFAIVを投与した子豚は、投与しなかった子豚と比較し、生存率が高まった。 The piglets that received DFAIII and DFAIV had an increased survival rate compared to the piglets that did not.
以上の結果から、新生子牛や新生子豚にDFAIII 及び/又はDFAIVを投与することにより、造血機能が改善され、生存率が高まることが明らかとなった。 From the above results, it was revealed that administration of DFAIII and / or DFAIV to newborn calves and newborn piglets improved the hematopoietic function and increased the survival rate.
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