JP2021029208A - Alcohol metabolism promoting composition - Google Patents
Alcohol metabolism promoting composition Download PDFInfo
- Publication number
- JP2021029208A JP2021029208A JP2019155895A JP2019155895A JP2021029208A JP 2021029208 A JP2021029208 A JP 2021029208A JP 2019155895 A JP2019155895 A JP 2019155895A JP 2019155895 A JP2019155895 A JP 2019155895A JP 2021029208 A JP2021029208 A JP 2021029208A
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- Prior art keywords
- lactoferrin
- alcohol
- ethanol
- alcohol metabolism
- liver
- 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.)
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Images
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Abstract
Description
本発明は、ラクトフェリン及び/又はラクトフェリン加水分解物を含有する、アルコール代謝促進のために用いられる組成物に関する。 The present invention relates to compositions used for promoting alcohol metabolism, which contain lactoferrin and / or lactoferrin hydrolyzate.
アルコール飲料は、古くから人々に親しまれているが、その過剰な摂取は望ましくない症状を引き起こすことがある。摂取したエタノール(アルコール)は、肝臓の酵素であるアルコールデヒドロゲナーゼ(ADH)によりアセトアルデヒドに代謝された後、アセトアルデヒドデヒドロゲナーゼ(ALDH)により酢酸に代謝され、無毒化される。過剰な飲酒では、エタノールやアセトアルデヒドの代謝が追い付かず、悪酔いや二日酔いを引き起こし、翌日以降にも頭痛やめまい、吐き気、脱水症状等が続くことがある。また、長期にわたって過剰な飲酒が続くと、肝臓にダメージが蓄積し、肝機能障害や高尿酸血症・痛風等の発症に至ることもある。アスパラギン酸アミノトランスフェラーゼ(AST)やアラニンアミノトランスフェラーゼ(ALT)等の肝機能を評価する酵素値は、健康診断における生化学検査でもなじみがある指標であるため、肝機能評価値の改善には一般に関心が高い。これらの症状や肝機能評価値の悪化はいずれも、摂取したエタノールとその中間代謝物であるアセトアルデヒドの毒性に起因することがあるため、アルコールの代謝を促し、速やかに無毒化すことが有効な解消手段となる。
これまでに、アルコール代謝を促進するための種々の有効成分が提案されている(特許文献1〜4等)。
Alcoholic beverages have long been familiar to people, but excessive intake can cause unwanted symptoms. The ingested ethanol (alcohol) is metabolized to acetaldehyde by the liver enzyme alcohol dehydrogenase (ADH) and then metabolized to acetic acid by acetaldehyde dehydrogenase (ALDH) to detoxify it. Excessive drinking may not keep up with the metabolism of ethanol and acetaldehyde, causing hangover and hangover, and headache, dizziness, nausea, dehydration, etc. may continue the next day or later. In addition, if excessive drinking continues for a long period of time, damage to the liver may accumulate, leading to the onset of liver dysfunction, hyperuricemia, gout, and the like. Enzyme values that evaluate liver function, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), are familiar indicators in biochemical tests in health examinations, so there is general interest in improving liver function evaluation values. Is high. Both of these symptoms and deterioration of liver function evaluation values may be due to the toxicity of ingested ethanol and its intermediate metabolite acetaldehyde. Therefore, it is effective to promote the metabolism of alcohol and quickly detoxify it. It becomes a means.
So far, various active ingredients for promoting alcohol metabolism have been proposed (
ところで、近年、乳タンパク質の一つであるラクトフェリン(以下、「LF」とも記す)及びその加水分解物には種々の機能が見出されており、機能性飲食品や医薬品へ適用されている(特許文献5等)。
LF及びその加水分解物に見出された機能としては、アルコールに起因しない肝機能障害の改善効果、具体的にはインターロイキン(IL)−11産生誘導による薬剤誘導性の肝障害改善効果や、非アルコール性脂肪肝炎(NASH)改善効果も報告されている(特許文献6〜7、非特許文献1)。
しかしながら、LF及びその加水分解物が、アルコール代謝を促進し得ることは知られていなかったし、アルコール代謝の低下又は異常に起因する疾患又は症状に対する有効性も知られていなかった。
By the way, in recent years, lactoferrin (hereinafter, also referred to as "LF"), which is one of the milk proteins, and its hydrolyzate have been found to have various functions, and are applied to functional foods and drinks and pharmaceuticals (hereinafter, also referred to as "LF"). Patent Document 5 etc.).
The functions found in LF and its hydrolysates include the effect of improving liver dysfunction not caused by alcohol, specifically, the effect of inducing interleukin (IL) -11 production to improve drug-induced liver damage. Non-alcoholic steatohepatitis (NASH) improving effect has also been reported (Patent Documents 6 to 7, Non-Patent Document 1).
However, it was not known that LF and its hydrolyzate could promote alcohol metabolism, nor was it known to be effective against diseases or symptoms caused by decreased or abnormal alcohol metabolism.
本発明は、アルコール代謝を促進する技術を提供することを課題とする。 An object of the present invention is to provide a technique for promoting alcohol metabolism.
本発明者らは、上記の課題を解決すべく鋭意研究を行った結果、ラクトフェリン及び/又はラクトフェリン加水分解物を摂取又は投与することにより、摂取したアルコールの代謝が促進することを見出し、本発明を完成するに至った。 As a result of diligent research to solve the above problems, the present inventors have found that ingestion or administration of lactoferrin and / or lactoferrin hydrolyzate promotes the metabolism of the ingested alcohol. Has been completed.
すなわち、本発明は、ラクトフェリン及び/又はラクトフェリン加水分解物を有効成分として含有する、アルコール代謝促進用組成物である。
好ましい態様では、本発明の組成物は肝機能を評価する酵素値の改善のために用いられる。かかる態様において、前記酵素はAST又はALTであることが好ましい。
別の好ましい態様では、本発明の組成物は、アルコール代謝の低下又は異常に起因する疾患又は症状の予防に用いられる。かかる態様において、前記疾患又は症状は、アルコール性肝障害、アルコール性鉄欠乏、アルコール性精巣障害、高尿酸血症、二日酔い、高コレステロール血症から選択される何れかであることが好ましい。
本発明の組成物は、飲食品であることが好ましい。
本発明の組成物は、医薬品であることが好ましい。
That is, the present invention is a composition for promoting alcohol metabolism containing lactoferrin and / or a lactoferrin hydrolyzate as an active ingredient.
In a preferred embodiment, the compositions of the invention are used to improve enzyme levels that assess liver function. In such an embodiment, the enzyme is preferably AST or ALT.
In another preferred embodiment, the compositions of the present invention are used for the prevention of diseases or symptoms resulting from decreased or abnormal alcohol metabolism. In such an embodiment, the disease or symptom is preferably selected from alcoholic liver disorder, alcoholic iron deficiency, alcoholic testis disorder, hyperuricemia, hangover, and hypercholesterolemia.
The composition of the present invention is preferably a food or drink.
The composition of the present invention is preferably a pharmaceutical product.
本発明によれば、アルコールの代謝を促進させることができる組成物が提供される。かかる組成物は、添加物等の態様で、飲食品や医薬品に含有させることができる。 According to the present invention, there is provided a composition capable of promoting the metabolism of alcohol. Such a composition can be contained in foods and drinks and pharmaceuticals in the form of additives and the like.
次に、本発明を詳細に説明する。ただし、本発明は以下の実施形態に限定されず、本発明の範囲内で自由に変更することができるものである。 Next, the present invention will be described in detail. However, the present invention is not limited to the following embodiments, and can be freely changed within the scope of the present invention.
本発明の組成物は、ラクトフェリン及び/又はラクトフェリン加水分解物を有効成分として含有する。 The composition of the present invention contains lactoferrin and / or a lactoferrin hydrolyzate as an active ingredient.
ラクトフェリンは、哺乳動物、例えば、ヒツジ、ヤギ、ブタ、マウス、水牛、ラクダ、ヤク、ウマ、ロバ、ラマ、ウシ又はヒトの乳、涙、唾液、血液等に含まれる鉄結合性の糖タンパク質である。
本発明におけるラクトフェリンは、いずれの哺乳動物に由来するものであってもよく、特に限定されないが、含有量や入手容易性の点から、例えば、ウシ、ヒト等の乳由来のラクトフェリンが好ましい。前記乳としては、初乳、移行乳、常乳、末期乳のいずれでもよい。
また、本発明におけるラクトフェリンは、前記乳の処理物である脱脂乳、ホエイ等から常法(例えば、イオンクロマトグラフィー等)によって分離されたラクトフェリン、遺伝子操作によって微生物、動物細胞、トランスジェニック動物等から産生された組換えラクトフェリン、合成ラクトフェリン、又はそれらの混合物でもよい。また、ラクトフェリンは、非グリコシル化又はグリコシル化されたものでもよい。このようなラクトフェリンとして、工業的規模で製造されている市販のラクトフェリン(例えば、森永乳業社製等)を使用することができる。
Lactoferrin is an iron-binding glycoprotein contained in mammals such as sheep, goats, pigs, mice, buffaloes, camels, yaks, horses, donkeys, llamas, cows or human milk, tears, saliva, blood, etc. is there.
The lactoferrin in the present invention may be derived from any mammal, and is not particularly limited, but from the viewpoint of content and availability, for example, lactoferrin derived from milk of cows, humans and the like is preferable. The milk may be initial milk, transition milk, normal milk, or terminal milk.
Further, the lactoferrin in the present invention is derived from lactoferrin separated from defatted milk, whey, etc., which are processed products of the milk, by a conventional method (for example, ion chromatography, etc.), from microorganisms, animal cells, transgenic animals, etc. by genetic engineering. It may be recombinant lactoferrin produced, synthetic lactoferrin, or a mixture thereof. In addition, lactoferrin may be non-glycosylated or glycosylated. As such lactoferrin, commercially available lactoferrin manufactured on an industrial scale (for example, manufactured by Morinaga Milk Industry Co., Ltd.) can be used.
本発明におけるラクトフェリン中の金属含有量は特に限定されず、ラクトフェリンを塩酸やクエン酸等により脱鉄したアポ型ラクトフェリン;該アポ型ラクトフェリンを、鉄、銅、亜鉛、マンガン等の金属でキレートさせて得られる飽和度100%以上の状態の金属飽和型ラクトフェリン;及び100%未満の各種飽和度で金属が結合している状態の金属部分飽和型ラクトフェリンからなる群から選ばれる、いずれか1種又は2種以上の混合物を用いることができる。 The metal content in lactoferrin in the present invention is not particularly limited, and apo-type lactoferrin obtained by deironing lactoferrin with hydrochloric acid, citric acid or the like; the apo-type lactoferrin is chelated with a metal such as iron, copper, zinc or manganese. Any one or 2 selected from the group consisting of the obtained metal-saturated lactoferrin having a saturation of 100% or more; and the metal partially saturated lactoferrin having a metal bonded at various saturations of less than 100%. Mixtures of seeds and above can be used.
ここで、本技術に用いられるラクトフェリンの調製(乳等の原料からのラクトフェリンの分離、精製)方法の一例を以下に示すが、これに限定されるものではない。
ウシ由来の乳原料を陽イオン交換カラムに通液し、この通過液を回収し、適宜この通過液を繰り返しカラムに通液する。このカラムに脱イオン水を通液し、食塩水を通液し、この陽イオン交換カラムに吸着した塩基性タンパク質の溶出液を得る。この溶出液からタンパク質を回収し、適宜洗浄し、脱イオン水にて溶解し、この溶解液を限外ろ過膜にてろ過する。さらに、脱塩処理、凍結乾燥することで、粉末状のラクトフェリンが得られる。
Here, an example of a method for preparing lactoferrin (separation and purification of lactoferrin from a raw material such as milk) used in the present technology is shown below, but the present invention is not limited thereto.
A bovine-derived dairy raw material is passed through a cation exchange column, the passing liquid is collected, and this passing liquid is repeatedly passed through the column as appropriate. Deionized water is passed through this column, and saline is passed through this column to obtain an eluate of the basic protein adsorbed on this cation exchange column. Protein is recovered from this eluate, washed appropriately, dissolved in deionized water, and the solution is filtered through an ultrafiltration membrane. Further, by desalting and freeze-drying, powdered lactoferrin can be obtained.
より詳細には、まず、イオン交換体をカラムに充填し、塩酸を通液し、水洗してイオン交換体を平衡化する。続いて、4℃に冷却したpH6.9の脱脂乳をカラムに通液し、透過液を回収し、再度同様にカラムに通液する。次いで、脱イオン水をカラムに通液し、食塩水を通液し、イオン交換体に吸着した塩基性タンパク質の溶出液を得る。この溶出液から回収したタンパク質を洗浄し、脱イオン水を添加して溶解し、得られた溶液を限外ろ過膜モジュールを用いて脱塩し、凍結乾燥して、粉末状ウシラクトフェリンを得る。このようにして、純度が95質量%以上のウシラクトフェリンが得られる。 More specifically, first, the column is filled with an ion exchanger, hydrochloric acid is passed through the column, and the column is washed with water to equilibrate the ion exchanger. Subsequently, skim milk having a pH of 6.9 cooled to 4 ° C. is passed through the column, the permeated liquid is collected, and the liquid is passed through the column again in the same manner. Then, deionized water is passed through the column, and saline solution is passed through the column to obtain an eluate of the basic protein adsorbed on the ion exchanger. The protein recovered from this eluate is washed, dissolved by adding deionized water, and the obtained solution is desalted using an ultrafiltration membrane module and freeze-dried to obtain powdered bovine lactoferrin. In this way, bovine lactoferrin having a purity of 95% by mass or more can be obtained.
ラクトフェリンにおいては、種、属、個体等の違いによって、1又は複数の位置での1
又は複数の塩基の置換、欠失、挿入、付加、又は逆位等の遺伝子変異が当然存在し、このような変異を有する遺伝子がコードするタンパク質のアミノ酸においても変異が生じている場合がある。本発明における本技術に用いることができるラクトフェリンには、本発明の効果を損なわない限りにおいて、このような変異を含むものも含有される。
また、本発明におけるラクトフェリンには、本発明の効果を損なわない限りにおいて、熱処理、酸処理、又はアルカリ処理を行ったラクトフェリン処理物も含まれてもよい。
In lactoferrin, 1 at one or more positions depending on the species, genus, individual, etc.
Alternatively, gene mutations such as substitutions, deletions, insertions, additions, or inversions of a plurality of bases naturally exist, and mutations may also occur in the amino acids of proteins encoded by genes having such mutations. The lactoferrin that can be used in the present technology in the present invention includes those containing such mutations as long as the effects of the present invention are not impaired.
In addition, the lactoferrin in the present invention may also include a lactoferrin-treated product that has been heat-treated, acid-treated, or alkaline-treated, as long as the effects of the present invention are not impaired.
本発明におけるラクトフェリン加水分解物は、前述のラクトフェリンを加水分解処理したものをいう。
加水分解処理としては、例えば特開2012−235768号公報に記載された方法が挙げられる。
具体的には、ラクトフェリン溶液を酵素反応処理を行う前に、塩酸、クエン酸、酢酸等の酸によりpHを2〜4、好ましくは2.5〜3.5、特に好ましくはpH3に調整する。
pHを調整したラクトフェリン溶液に、タンパク質分解酵素を所望の量で添加した後、酵素反応の温度を35〜55℃、好ましくは40〜50℃、より好ましくは42〜48℃に保持して、6時間〜24時間、好ましくは12〜18時間、攪拌しながらラクトフェリンを加水分解させる。
次いで、例えば反応溶液を80℃に昇温して10分間維持し、酵素を加熱失活させる。さらに、好ましくは、水酸化ナトリウム溶液等のアルカリ溶液を添加して、pHを5〜7、例えば6に調整する。
なお、pH調整後の反応溶液(ラクトフェリン加水分解物)は、溶液のままでもよいが、凍結乾燥等を行って粉末化することが好ましい。また、ラクトフェリン分解物は、クロマトグラフィー、又は限外濾過等により、分画したものを用いることもできる。
The lactoferrin hydrolyzate in the present invention refers to the above-mentioned lactoferrin hydrolyzed.
Examples of the hydrolysis treatment include the methods described in JP2012-235768A.
Specifically, the pH of the lactoferrin solution is adjusted to 2 to 4, preferably 2.5 to 3.5, particularly preferably pH 3 with an acid such as hydrochloric acid, citric acid, or acetic acid before the enzymatic reaction treatment.
After adding the proteolytic enzyme in a desired amount to the pH-adjusted lactoferrin solution, the temperature of the enzyme reaction was maintained at 35 to 55 ° C., preferably 40 to 50 ° C., more preferably 42 to 48 ° C., 6 The lactoferrin is hydrolyzed with stirring for hours to 24 hours, preferably 12 to 18 hours.
Then, for example, the reaction solution is heated to 80 ° C. and maintained for 10 minutes to inactivate the enzyme by heating. Further, preferably, an alkaline solution such as a sodium hydroxide solution is added to adjust the pH to 5 to 7, for example 6.
The pH-adjusted reaction solution (lactoferrin hydrolyzate) may remain as a solution, but it is preferably lyophilized and pulverized. Further, as the lactoferrin decomposition product, one fractionated by chromatography, ultrafiltration or the like can also be used.
本態様の組成物において、ラクトフェリン及び/又はラクトフェリン加水分解物の組成物全体に対する含有量は、好ましくは0.001質量%以上100質量%未満、より好ましくは0.005〜75質量%、さらに好ましくは0.01〜50質量%である。 In the composition of this embodiment, the content of lactoferrin and / or lactoferrin hydrolyzate with respect to the whole composition is preferably 0.001% by mass or more and less than 100% by mass, more preferably 0.005 to 75% by mass, still more preferably. Is 0.01 to 50% by mass.
本発明の組成物は、アルコールの代謝を促進させることができる。
ここで、「代謝促進」とは、体内に摂取されたエタノール及びその中間代謝産物であるアセトアルデヒドの量を代謝によって低減させる程度が無処置の場合に比して大きいこと、及び血中エタノール、アセトアルデヒド濃度が上昇するのを無処置の場合に比して抑制・防止することを含む。
なお、本明細書においてアルコールはエタノールと同義とする。
The composition of the present invention can promote the metabolism of alcohol.
Here, "promoting metabolism" means that the amount of ethanol ingested in the body and acetaldehyde, which is an intermediate metabolite thereof, is reduced by metabolism more than in the case of no treatment, and blood ethanol and acetaldehyde. It includes suppressing / preventing the increase in concentration as compared with the case of no treatment.
In this specification, alcohol is synonymous with ethanol.
アルコールの代謝が促進されると、血中エタノール、アセトアルデヒド濃度が低下するため、血中エタノール、アセトアルデヒド濃度の上昇に起因する疾患又は症状、すなわちアルコール代謝の低下又は異常に起因する疾患又は症状を予防することができる。かかる疾患又は症状としては、例えば、アルコール性肝障害、アルコール性鉄欠乏、アルコール性精巣障害、高尿酸血症、二日酔い、高コレステロール血症などが挙げられる。
アルコール性肝障害としては、さらに具体的には例えば、アルコール性脂肪肝、アルコール性肝線維症、及びアルコール性肝硬変のような慢性肝炎、及び、アルコール性肝炎のような急性肝炎が挙げられる。
ここで、疾患又は症状の「予防」とは、適用対象における疾患又は症状の発生を防止すること、該発生を遅延させること、該発生の危険性を低下させることを含む。また、すでに適用対象が罹患(発症)している場合であっても、疾患又は症状のさらなる進行を抑制することも、「予防」に包含されてもよい。
When alcohol metabolism is promoted, blood ethanol and acetaldehyde concentrations decrease, thus preventing diseases or symptoms caused by increased blood ethanol and acetaldehyde concentrations, that is, diseases or symptoms caused by decreased or abnormal alcohol metabolism. can do. Such diseases or symptoms include, for example, alcoholic liver disorder, alcoholic iron deficiency, alcoholic testis disorder, hyperuricemia, hangover, hypercholesterolemia and the like.
More specifically, alcoholic liver disease includes chronic hepatitis such as alcoholic fatty liver, alcoholic liver fibrosis, and alcoholic cirrhosis, and acute hepatitis such as alcoholic hepatitis.
Here, "prevention" of a disease or symptom includes preventing the occurrence of the disease or symptom in the application target, delaying the occurrence, and reducing the risk of the occurrence. Further, even when the target of application is already affected (onset), suppressing the further progression of the disease or symptom may be included in "prevention".
アルコールの代謝が促進したことや、アルコール代謝の低下又は異常に起因する疾患又
は症状の予防効果は、例えば、アルコール代謝酵素の活性又は発現量の測定、血中又は呼気中のエタノール、アセトアルデヒド濃度の測定、一般状態の観察、血中の肝機能を評価する酵素(例えば、アスパラギン酸アミノトランスフェラーゼ(AST)、アラニンアミノトランスフェラーゼ(ALT))値の測定、ヘマトクリット(HCT)値の測定、等の結果に基づいて確認することができる。
特に、ASTやALT等の肝機能を評価する酵素の測定値については、わかりやすい指標となり得る。
The promotion of alcohol metabolism and the preventive effect of diseases or symptoms caused by decreased or abnormal alcohol metabolism are, for example, measurement of activity or expression level of alcohol-metabolizing enzyme, concentration of ethanol and acetaldehyde in blood or exhaled breath. For the results of measurement, observation of general condition, measurement of enzymes that evaluate liver function in blood (for example, aspartate aminotransferase (AST), alanine aminotransferase (ALT)), measurement of hematocrit (HCT) value, etc. It can be confirmed based on.
In particular, the measured values of enzymes that evaluate liver function such as AST and ALT can be an easy-to-understand index.
これまでに、ラクトフェリン及び/又はラクトフェリン加水分解物が、アルコールに起因しない肝障害に対して改善効果を示すことは知られていた(特許文献6、非特許文献1)。
しかしながら、アルコールに起因する肝障害等の疾患や症状では、その発症の機序が異なると推察される。また、アルコールに起因しない肝障害に対しては、ラクトフェリンの方がその加水分解物よりも高い効果が得られることが示されているのに対し、後述の実施例に示されるようにアルコールに起因する疾患や症状に対しては、ラクトフェリン以上にその加水分解物の方が高い効果が得られることから、両効果は別の機序により得られる、区別されるものであると理解される。
実際に、後述の実施例に示されるとおり、ラクトフェリン及びラクトフェリン加水分解物はそれぞれ、アルコール代謝酵素の発現を増強させるため、本明細書で示される組成物の作用効果と用途は、従来ラクトフェリン及び/又はラクトフェリン加水分解物に認められていた作用効果と用途と明確に区別されるものである。
So far, it has been known that lactoferrin and / or lactoferrin hydrolyzate has an improving effect on liver damage not caused by alcohol (Patent Document 6, Non-Patent Document 1).
However, it is presumed that the mechanism of onset is different for diseases and symptoms such as liver damage caused by alcohol. In addition, it has been shown that lactoferrin is more effective than its hydrolyzate for liver damage not caused by alcohol, whereas it is caused by alcohol as shown in Examples described later. Since the hydrolyzate is more effective than lactoferrin for the disease or symptom, it is understood that both effects are obtained by different mechanisms and are distinguished.
In fact, as shown in Examples below, lactoferrin and lactoferrin hydrolyzate enhance the expression of alcohol-metabolizing enzymes, respectively. Alternatively, it is clearly distinguished from the effects and uses recognized in the lactoferrin hydrolyzate.
本発明の組成物は、それ自体を飲食品や医薬品等の形態としてもよいし、添加物として飲食品や医薬品等に含有させる形態としてもよい。
本発明の組成物の摂取(投与)経路は、経口又は非経口のいずれでもよいが、通常は経口である。また、非経口摂取(投与)としては、直腸投与等が挙げられる。
The composition of the present invention may itself be in the form of foods and drinks, pharmaceuticals and the like, or may be contained in foods and drinks and pharmaceuticals as an additive.
The route of ingestion (administration) of the composition of the present invention may be oral or parenteral, but is usually oral. In addition, as parenteral ingestion (administration), rectal administration and the like can be mentioned.
本発明の組成物を経口摂取(投与)するときの含有量としては、前述した組成物全体における含有量としてもよいし、適宜希釈等してもよい。例えば、経口摂取(投与)時のラクトフェリン及び/又はラクトフェリン加水分解物の組成物全体に対する含有量は、好ましくは0.001〜100質量%、より好ましくは0.005〜75質量%、さらに好ましくは0.01〜50質量%である。
これらは、通常、経口組成物として流通するときの含有量の範囲であってよい。
The content of the composition of the present invention when orally ingested (administered) may be the content in the entire composition described above, or may be appropriately diluted. For example, the content of lactoferrin and / or lactoferrin hydrolyzate with respect to the whole composition at the time of oral ingestion (administration) is preferably 0.001 to 100% by mass, more preferably 0.005 to 75% by mass, still more preferably. It is 0.01 to 50% by mass.
These may usually be in the range of content when distributed as an oral composition.
本発明の別の態様は、アルコール代謝促進用組成物の製造における、ラクトフェリン及び/又はラクトフェリン加水分解物の使用である。
本発明の別の態様は、アルコール代謝促進における、ラクトフェリン及び/又はラクトフェリン加水分解物の使用である。
本発明の別の態様は、アルコール代謝を促進させるために用いられる、ラクトフェリン及び/又はラクトフェリン加水分解物である。
本発明の別の態様は、ラクトフェリン及び/又はラクトフェリン加水分解物を動物に投与することを含む、アルコール代謝を促進させる方法である。ここで、動物は、特に限定されないが、通常はヒトである。
Another aspect of the present invention is the use of lactoferrin and / or lactoferrin hydrolyzate in the production of alcohol metabolism promoting compositions.
Another aspect of the invention is the use of lactoferrin and / or lactoferrin hydrolyzate in promoting alcohol metabolism.
Another aspect of the invention is lactoferrin and / or a lactoferrin hydrolyzate used to promote alcohol metabolism.
Another aspect of the invention is a method of promoting alcohol metabolism, which comprises administering lactoferrin and / or a lactoferrin hydrolyzate to an animal. Here, the animal is not particularly limited, but is usually a human.
本発明の組成物の摂取(投与)時期は、特に限定されず、投与対象の状態に応じて適宜選択することが可能である。 The ingestion (administration) timing of the composition of the present invention is not particularly limited, and can be appropriately selected according to the condition of the administration target.
本発明の組成物の摂取(投与)量は、摂取(投与)対象の年齢、性別、状態、その他の条件等により適宜選択される。
本発明の組成物の摂取(投与)量は、ラクトフェリン及び/又はラクトフェリン加水分
解物の摂取量として、例えば、成人において、好ましくは10〜10000mg/日、より好ましくは50〜3000mg/日、さらに好ましくは100〜600mg/日の範囲となる量を目安とするのがよい。
なお、摂取(投与)の量や期間にかかわらず、薬剤は1日1回又は複数回に分けて投与することができる。
The ingestion (administration) amount of the composition of the present invention is appropriately selected depending on the age, sex, condition, other conditions, etc. of the ingestion (administration) subject.
The intake (administration) amount of the composition of the present invention is preferably 10 to 10000 mg / day, more preferably 50 to 3000 mg / day, more preferably 50 to 3000 mg / day, for example, in an adult, as the intake of lactoferrin and / or lactoferrin hydrolyzate. It is recommended to use an amount in the range of 100 to 600 mg / day as a guide.
The drug can be administered once a day or in multiple divided doses regardless of the amount and duration of ingestion (administration).
本発明の組成物は、飲食品の態様とすることが好ましい。
飲食品としては、本発明の効果を損なわないものであれば形態や性状は特に制限されず、通常飲食品に用いられる原料を用いて通常の方法によって製造することができる。
なお、飲食品に添加する添加物の態様も本発明の組成物に含まれる。
飲食品は、通常は経口摂取されるものであるが、これに限られず、例えば経鼻摂取されるもの、胃瘻や腸瘻により摂取されるものでもよい。
The composition of the present invention is preferably in the form of food and drink.
The form and properties of the food and drink are not particularly limited as long as the effects of the present invention are not impaired, and the food and drink can be produced by a usual method using the raw materials usually used for food and drink.
The aspect of the additive added to the food or drink is also included in the composition of the present invention.
The food and drink are usually taken orally, but are not limited to this, and may be, for example, nasally ingested, or ingested by a gastrostomy or an intestinal fistula.
飲食品としては、液状、ペースト状、ゲル状固体、粉末等の形態を問わず、例えば、錠菓;流動食(経管摂取用栄養食);パン、マカロニ、スパゲッティ、めん類、ケーキミックス、から揚げ粉、パン粉等の小麦粉製品;即席めん、カップめん、レトルト・調理食品、調理缶詰め、電子レンジ食品、即席スープ・シチュー、即席みそ汁・吸い物、スープ缶詰め、フリーズ・ドライ食品、その他の即席食品等の即席食品類;農産缶詰め、果実缶詰め、ジャム・マーマレード類、漬物、煮豆類、農産乾物類、シリアル(穀物加工品)等の農産加工品;水産缶詰め、魚肉ハム・ソーセージ、水産練り製品、水産珍味類、つくだ煮類等の水産加工品;畜産缶詰め・ペースト類、畜肉ハム・ソーセージ等の畜産加工品;加工乳、乳飲料、ヨーグルト類、乳酸菌飲料類、チーズ、アイスクリーム類、クリーム、その他の乳製品等の乳・乳製品;バター、マーガリン類、植物油等の油脂類;しょうゆ、みそ、ソース類、トマト加工調味料、みりん類、食酢類等の基礎調味料;調理ミックス、カレーの素類、たれ類、ドレッシング類、めんつゆ類、スパイス類、その他の複合調味料等の複合調味料・食品類;素材冷凍食品、半調理冷凍食品、調理済冷凍食品等の冷凍食品;キャラメル、キャンディー、チューインガム、チョコレート、クッキー、ビスケット、ケーキ、パイ、スナック、クラッカー、和菓子、米菓子、豆菓子、デザート菓子、ゼリー、その他の菓子などの菓子類;炭酸飲料、天然果汁、果汁飲料、果汁入り清涼飲料、果肉飲料、果粒入り果実飲料、野菜系飲料、豆乳、豆乳飲料、コーヒー飲料、お茶飲料、粉末飲料、濃縮飲料、スポーツ飲料、栄養飲料、アルコール飲料、その他の嗜好飲料等の嗜好飲料類、ベビーフード、ふりかけ、お茶漬けのり等のその他の市販食品等;サプリメント、調製乳(粉乳、液状乳等を含む)等の栄養組成物;経腸栄養食;機能性食品(特定保健用食品、栄養機能食品)等が挙げられる。 Foods and drinks may be in the form of liquid, paste, gel solid, powder, etc., for example, from tablet confectionery; liquid food (nutrient food for tube intake); bread, macaroni, spaghetti, noodles, cake mix, etc. Wheat flour products such as fried flour and bread flour; instant noodles, cup noodles, retort / cooked foods, canned foods, microwave foods, instant soups / stews, instant miso soup / suckers, canned soups, freeze / dry foods, and other instant foods. Instant foods; canned agricultural products, canned fruits, jams and marmalades, pickles, boiled beans, dried agricultural products, processed agricultural products such as cereals (processed grain products); canned fishery products, fish hams and sausages, fish paste products, fishery delicacies , Processed marine products such as simmered Tsukuda; Canned livestock / pastes, Processed livestock products such as livestock ham / sausage; Processed milk, dairy drinks, yogurts, lactic acid bacteria drinks, cheese, ice creams, creams, and other dairy products Milk and dairy products such as butter, margarines, vegetable oils and other fats and oils; soy sauce, miso, sauces, tomato processing seasonings, mirins, vinegars and other basic seasonings; cooking mixes, curry ingredients, sauces, etc. Frozen foods such as ingredients, dressings, noodles, spices, and other complex seasonings; frozen foods such as frozen foods, semi-cooked frozen foods, and cooked frozen foods; caramel, candy, chewing gum, chocolate , Cookies, biscuits, cakes, pies, snacks, crackers, Japanese confectionery, rice confectionery, bean confectionery, dessert confectionery, jelly, and other confectionery; carbonated beverages, natural fruit juice, fruit juice beverages, refreshing beverages with fruit juice, fruit meat beverages. , Fruit drinks with fruits, vegetable drinks, soy milk, soy milk drinks, coffee drinks, tea drinks, powder drinks, concentrated drinks, sports drinks, nutritional drinks, alcoholic drinks, other favorite drinks, baby food, Other commercial foods such as sprinkles and Ochazuke paste; nutritional compositions such as supplements and prepared milk (including powdered milk, liquid milk, etc.); enteric nutritional foods; functional foods (foods for specified health use, nutritionally functional foods), etc. Can be mentioned.
また、飲食品の一態様として飼料とすることもできる。飼料としては、ペットフード、家畜飼料、養魚飼料等が挙げられる。
飼料の形態としては特に制限されず、例えば、トウモロコシ、小麦、大麦、ライ麦、マイロ等の穀類;大豆油粕、ナタネ油粕、ヤシ油粕、アマニ油粕等の植物性油粕類;フスマ、麦糠、米糠、脱脂米糠等の糠類;コーングルテンミール、コーンジャムミール等の製造粕類;魚粉、脱脂粉乳、ホエイ、イエローグリース、タロー等の動物性飼料類;トルラ酵母、ビール酵母等の酵母類;第三リン酸カルシウム、炭酸カルシウム等の鉱物質飼料;油脂類;単体アミノ酸;糖類等を含有するものであってよい。
It can also be used as feed as one aspect of food and drink. Examples of the feed include pet food, livestock feed, fish feed and the like.
The form of the feed is not particularly limited, and for example, cereals such as corn, wheat, barley, rye, and mylo; vegetable oil lees such as soybean oil lees, rapeseed oil lees, palm oil lees, and flaxseed oil lees; bran, wheat bran, rice bran, etc. Bran such as defatted rice bran; Manufactured cereals such as corn gluten meal and corn jam meal; Animal feeds such as fish flour, defatted milk powder, whey, yellow grease and tallow; Yeasts such as tolla yeast and beer yeast; It may contain mineral feeds such as calcium phosphate and calcium carbonate; fats and oils; simple amino acids; sugars and the like.
本発明の組成物が飲食品(飼料を含む)の態様である場合、アルコール代謝促進という用途やそれに関連する用途が表示された飲食品として提供・販売されることが可能である。 When the composition of the present invention is in the form of food and drink (including feed), it can be provided and sold as food and drink in which the use for promoting alcohol metabolism and the related use are indicated.
かかる「表示」行為には、需要者に対して前記用途を知らしめるための全ての行為が含まれ、前記用途を想起・類推させうるような表現であれば、表示の目的、表示の内容、表
示する対象物・媒体等の如何に拘わらず、全て本発明の「表示」行為に該当する。
また、「表示」は、需要者が上記用途を直接的に認識できるような表現により行われることが好ましい。具体的には、飲食品に係る商品又は商品の包装に前記用途を記載したものを譲渡し、引き渡し、譲渡若しくは引き渡しのために展示し、輸入する行為、商品に関する広告、価格表若しくは取引書類に上記用途を記載して展示し、若しくは頒布し、又はこれらを内容とする情報に上記用途を記載して電磁気的(インターネット等)方法により提供する行為等が挙げられる。
Such "display" act includes all acts for informing the consumer of the use, and if it is an expression that can recall or analogize the use, the purpose of the display, the content of the display, etc. Regardless of the object or medium to be displayed, all of them fall under the "display" act of the present invention.
Further, it is preferable that the "display" is performed by an expression that allows the consumer to directly recognize the above-mentioned use. Specifically, the act of transferring a product related to food and drink or the packaging of the product with the above-mentioned use, displaying it for delivery, transfer or delivery, and importing it, advertising on the product, price list or transaction documents Examples include the act of describing the above-mentioned use and displaying or distributing it, or describing the above-mentioned use in the information containing these and providing it by an electromagnetic (Internet, etc.) method.
一方、表示内容としては、行政等によって認可された表示(例えば、行政が定める各種制度に基づいて認可を受け、そのような認可に基づいた態様で行う表示等)であることが好ましい。また、そのような表示内容を、包装、容器、カタログ、パンフレット、POP等の販売現場における宣伝材、その他の書類等へ付することが好ましい。 On the other hand, as the display content, it is preferable that the display is approved by the government or the like (for example, a display obtained based on various systems established by the government and performed in a manner based on such approval). In addition, it is preferable to attach such display contents to packaging, containers, catalogs, pamphlets, promotional materials such as POPs at sales sites, and other documents.
また、「表示」には、健康食品、機能性食品、経腸栄養食品、特別用途食品、保健機能食品、特定保健用食品、栄養機能食品、機能性表示食品、医薬用部外品等としての表示も挙げられる。この中でも特に、消費者庁によって認可される表示、例えば、特定保健用食品、栄養機能食品、若しくは機能性表示食品に係る制度、又はこれらに類似する制度にて認可される表示等が挙げられる。具体的には、特定保健用食品としての表示、条件付き特定保健用食品としての表示、身体の構造や機能に影響を与える旨の表示、疾病リスク減少表示、科学的根拠に基づいた機能性の表示等を挙げることができ、より具体的には、健康増進法に規定する特別用途表示の許可等に関する内閣府令(平成二十一年八月三十一年内閣府令第五十七号)に定められた特定保健用食品としての表示(特に保健の用途の表示)及びこれに類する表示が典型的な例である。
かかる表示としては、肝機能を評価する指標である酵素値(AST、ALT等)について、アルコール摂取に伴う酵素値の低下の改善に役立つ旨を示すことができ、例えば、「アルコール摂取に伴う肝機能の数値低下を改善したい方へ」、「アルコールの摂取から肝臓を守るために」、「二日酔い予防用」、「お酒の飲みすぎによる諸症状を防ぎたいときに」等と表示することが挙げられる。
In addition, "labeling" includes health foods, functional foods, enteric nutritional foods, special purpose foods, health functional foods, specified health foods, nutritional functional foods, functional foods, non-medicinal products, etc. The display is also mentioned. Among these, in particular, labeling approved by the Consumer Affairs Agency, for example, a system related to foods for specified health use, foods with nutritional function, or foods with functional claims, or labeling approved by a system similar to these, and the like can be mentioned. Specifically, labeling as a food for specified health use, labeling as a conditional food for specified health use, labeling to the effect that it affects the structure and function of the body, labeling for reducing the risk of illness, and functionality based on scientific grounds. Indications, etc. can be mentioned, and more specifically, Cabinet Office Ordinance on permission for special use indications stipulated in the Health Promotion Act (Cabinet Office Ordinance No. 57, August 31, 2001) Labeling as a food for specified health use (particularly labeling for health use) and similar labeling specified in the above are typical examples.
As such a display, it can be shown that the enzyme value (AST, ALT, etc.), which is an index for evaluating the liver function, is useful for improving the decrease in the enzyme level due to alcohol intake. "For those who want to improve the decrease in function values", "To protect the liver from alcohol intake", "For hangover prevention", "When you want to prevent various symptoms caused by drinking too much alcohol", etc. can be displayed. Can be mentioned.
本発明の組成物が、医薬品の形態である場合、その投与経路は、経口又は非経口のいずれでもよいが経口が好ましい。また、非経口摂取(投与)としては、直腸投与等が挙げられる。
医薬品の形態としては、投与方法に応じて、適宜所望の剤形に製剤化することができる。例えば、経口投与の場合、散剤、顆粒剤、錠剤、カプセル剤等の固形製剤;溶液剤、シロップ剤、懸濁剤、乳剤等の液剤等に製剤化することができる。また、非経口投与の場合、座剤、軟膏剤、注射剤等に製剤化することができる。
製剤化に際しては、通常製剤化に用いられている賦形剤、pH調整剤、着色剤、矯味剤等の成分を用いることができる。また、他の薬効成分や、公知の又は将来的に見出されるアルコール代謝促進成分などを併用することも可能である。
加えて、製剤化は剤形に応じて適宜公知の方法により実施できる。製剤化に際しては、適宜、製剤担体を配合して製剤化してもよい。
When the composition of the present invention is in the form of a pharmaceutical product, the route of administration thereof may be oral or parenteral, but oral is preferable. In addition, as parenteral ingestion (administration), rectal administration and the like can be mentioned.
As the form of the drug, it can be appropriately formulated into a desired dosage form according to the administration method. For example, in the case of oral administration, it can be formulated into solid preparations such as powders, granules, tablets and capsules; liquid preparations such as solutions, syrups, suspensions and emulsions. In the case of parenteral administration, it can be formulated into a suppository, an ointment, an injection or the like.
At the time of formulation, components such as excipients, pH adjusters, colorants, and flavoring agents that are usually used for formulation can be used. It is also possible to use other medicinal ingredients, known or future alcohol metabolism promoting ingredients, and the like in combination.
In addition, formulation can be carried out by a known method as appropriate depending on the dosage form. At the time of formulation, a formulation carrier may be blended and formulated as appropriate.
賦形剤としては、例えば、乳糖、白糖、ブドウ糖、マンニット、ソルビット等の糖誘導体;トウモロコシデンプン、馬鈴薯デンプン、α−デンプン、デキストリン、カルボキシメチルデンプン等のデンプン誘導体;結晶セルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、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等のセルロース誘導体;アラビアゴム;デキストラン;プルラン;軽質無水珪酸、合成珪酸アルミニウム、メタ珪酸アルミン酸マグネシウム等の珪酸塩誘導体;リン酸カルシウム等のリン酸塩誘導体;炭酸カルシウム等の炭酸塩誘導体;硫酸カルシウム等の硫酸塩誘導体等が挙げられる。 Examples of excipients include sugar derivatives such as lactose, sucrose, glucose, mannit, and sorbit; starch derivatives such as corn starch, horse bell starch, α-starch, dextrin, and carboxymethyl starch; crystalline cellulose, hydroxypropyl cellulose, and the like. Cellulous derivatives such as hydroxypropylmethyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose calcium; gum arabic; dextran; purulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, magnesium aluminometasilicate; phosphate derivatives such as calcium phosphate; carbonic acid Carbonate derivatives such as calcium; sulfate derivatives such as calcium sulfate can be mentioned.
結合剤としては、例えば、上記賦形剤の他、ゼラチン;ポリビニルピロリドン;マクロゴール等が挙げられる。 Examples of the binder include gelatin; polyvinylpyrrolidone; macrogol and the like in addition to the above-mentioned excipients.
崩壊剤としては、例えば、上記賦形剤の他、クロスカルメロースナトリウム、カルボキシメチルスターチナトリウム、架橋ポリビニルピロリドン等の化学修飾されたデンプン又はセルロース誘導体等が挙げられる。 Examples of the disintegrant include, in addition to the above-mentioned excipients, chemically modified starch or cellulose derivatives such as croscarmellose sodium, carboxymethyl starch sodium, and crosslinked polyvinylpyrrolidone.
滑沢剤としては、例えば、タルク;ステアリン酸;ステアリン酸カルシウム、ステアリン酸マグネシウム等のステアリン酸金属塩;コロイドシリカ;ピーガム、ゲイロウ等のワックス類;硼酸;グリコール;フマル酸、アジピン酸等のカルボン酸類;安息香酸ナトリウム等のカルボン酸ナトリウム塩;硫酸ナトリウム等の硫酸塩類;ロイシン;ラウリル硫酸ナトリウム、ラウリル硫酸マグネシウム等のラウリル硫酸塩;無水珪酸、珪酸水和物等の珪酸類;デンプン誘導体等が挙げられる。 Examples of the lubricant include talc; stearic acid; metal stearate salts such as calcium stearate and magnesium sulfate; colloidal silica; waxes such as pea gum and gay wax; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid. Sodium carboxylic acid salts such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic acid anhydride and silicate hydrate; starch derivatives and the like. Be done.
安定剤としては、例えば、メチルパラベン、プロピルパラベン等のパラオキシ安息香酸エステル類;クロロブタノール、ベンジルアルコール、フェニルエチルアルコール等のアルコール類;塩化ベンザルコニウム;無水酢酸;ソルビン酸等が挙げられる。 Examples of the stabilizer include paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalconium chloride; acetic anhydride; and sorbic acid.
矯味矯臭剤としては、例えば、甘味料、酸味料、香料等が挙げられる。
なお、経口投与用の液剤の場合に使用する担体としては、水等の溶剤等が挙げられる。
Examples of the flavoring agent include sweeteners, acidulants, and flavors.
Examples of the carrier used in the case of a liquid preparation for oral administration include a solvent such as water.
本発明の医薬品を摂取するタイミングは、例えば食前、食後、食間、就寝前など特に限定されない。 The timing of ingesting the drug of the present invention is not particularly limited, for example, before meals, after meals, between meals, and before bedtime.
以下に実施例を用いて本発明をさらに具体的に説明するが、本発明はこれら実施例に限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples.
<実施例1>ラットのアルコール性肝障害モデルに対するラクトフェリン及びその加水分解物の影響の検討
(1)試料
ラクトフェリン試料(LF)は、森永乳業株式会社製MLF−EXを用いた。ラクトフェリン加水分解物試料(LF分解物)は、森永乳業株式会社製F1000を用いた。
比較試料として、カルボキシメチルセルロース(CMC)(関東化学株式会社製,ロット番号:603H1629)を用いた。
<Example 1> Examination of the effect of lactoferrin and its hydrolyzate on a rat alcoholic liver injury model (1) Sample As the lactoferrin sample (LF), MLF-EX manufactured by Morinaga Milk Industry Co., Ltd. was used. As the lactoferrin hydrolyzate sample (LF hydrolyzate), F1000 manufactured by Morinaga Milk Industry Co., Ltd. was used.
Carboxymethyl cellulose (CMC) (manufactured by Kanto Chemical Co., Inc., lot number: 603H1629) was used as a comparative sample.
(2)被検動物
ラット(Slc:Wistar (SPF),4週齢,雄、日本エスエルシー株式会社)を、入荷から7日間通常の条件で飼育した後、8匹ずつ4群(コントロール群、エタノール群、LF群、LF分解物群)に分けた。
(2) Test animals Rats (Slc: Wistar (SPF), 4 weeks old, male, Nippon SLC Co., Ltd.) were bred under normal conditions for 7 days after arrival, and then 8 animals each in 4 groups (control group, It was divided into an ethanol group, an LF group, and an LF decomposition product group).
(3)飼料
コントロール群には、通常飼料を自由摂取させ、またCMC0.5w/v%液を10mL/kg・日、経口投与した。
エタノール群には、エタノール含有飼料を自由摂取させ、またCMC0.5w/v%液を10mL/kg・日、経口投与した。
LF群には、エタノール含有飼料を自由摂取させ、またCMC0.5w/v%液にLFを終濃度3w/v%添加したものを、10mL/kg・日、経口投与した。
LF分解物群には、エタノール含有飼料を自由摂取させ、またCMC0.5w/v%液
にLF加水分解物を終濃度3w/v%添加したものを、10mL/kg・日、経口投与した。
エタノール含有飼料は、通常飼料に、試験開始1〜2日目は3w/v%、3〜4日目は4w/v%、5日目以降は5w/v%の終濃度でエタノールを添加したものである。
なお、水道水は自由摂取とした。
(3) The feed control group was allowed to freely ingest normal feed, and CMC 0.5 w / v% solution was orally administered at 10 mL / kg / day.
The ethanol group was allowed to freely ingest an ethanol-containing feed, and a CMC 0.5 w / v% solution was orally administered at 10 mL / kg / day.
The LF group was allowed to freely ingest an ethanol-containing feed, and a CMC 0.5 w / v% solution to which LF was added at a final concentration of 3 w / v% was orally administered at 10 mL / kg / day.
The LF hydrolyzate group was allowed to freely ingest an ethanol-containing feed, and a CMC 0.5 w / v% solution to which the LF hydrolyzate was added at a final concentration of 3 w / v% was orally administered at 10 mL / kg / day.
For the ethanol-containing feed, ethanol was added to the normal feed at a final concentration of 3 w / v% on the 1st and 2nd days after the start of the test, 4 w / v% on the 3rd to 4th days, and 5 w / v% on the 5th and subsequent days. It is a thing.
Tap water was taken freely.
(4)飼育及び検査等
各群に前述の飼料を摂取させ(摂取開始日を1日目とする)、42日間通常条件で飼育した。
毎日一般状態を観察し、週に一回体重を測定した。
14、28、及び42日目に、イソフルラン麻酔下で皮膚を切開し、頸静脈から0.2mLの採血を行い、定法に従い遠心分離して血清を分取した。得られた血清を用いて、血清中AST、ALT、TGおよびT−CHOを自動分析装置(日立自動分析装置3100)を用いて測定した.
43日目に体重を測定した後に解剖を行った。イソフルラン麻酔下で腹部大静脈より採血を行い、定法に従い遠心分離して血清を分取した。また、肝臓、精巣を摘出した。肝臓の鉄含有量を常法により測定した。また、肝臓におけるアルコール代謝酵素(adh1及びaldh2)の発現を、常法により測定した。
(4) Breeding and inspection, etc. Each group was allowed to ingest the above-mentioned feed (the intake start date is the first day), and the animals were bred under normal conditions for 42 days.
The general condition was observed daily and the body weight was measured once a week.
On days 14, 28, and 42, the skin was incised under isoflurane anesthesia, 0.2 mL of blood was collected from the jugular vein, and the serum was separated by centrifugation according to a conventional method. Using the obtained serum, AST, ALT, TG and T-CHO in serum were measured using an automatic analyzer (Hitachi automatic analyzer 3100).
On the 43rd day, the body weight was measured and then dissection was performed. Blood was collected from the abdominal vena cava under isoflurane anesthesia, and the serum was collected by centrifugation according to a conventional method. In addition, the liver and testis were removed. The iron content of the liver was measured by a conventional method. In addition, the expression of alcohol-metabolizing enzymes (adh1 and aldh2) in the liver was measured by a conventional method.
(5)統計処理
得られた数値は各群で平均値及び標準誤差を算出した。有意差検定はエタノール群を基準として群間比較した。統計手法はBartllet検定により等分散性の検定を行い、等分散の場合にはDunnettの多重比較検定を、不等分散の場合はSteelの多重比較検定を行った。有意水準は,Bartllet検定は危険率5%とした。Dunnettの多重比較検定及びSteelの多重比較検定では危険率5%及び1%とした。
(5) Statistical processing For the obtained numerical values, the average value and standard error were calculated for each group. The significance test was compared between groups based on the ethanol group. As a statistical method, the homoscedasticity test was performed by the Bartllet test, Dunnett's multiple comparison test was performed in the case of homoscedasticity, and Steel's multiple comparison test was performed in the case of unequal dispersion. The significance level was 5% for the Bartllet test. In Dunnett's multiple comparison test and Steel's multiple comparison test, the risk rates were 5% and 1%.
(6)結果
(i)生化学
14及び28日目の、血清AST値を図1及び表1に、血清ALT値を図2及び表1に、血清TG値を図3及び表1に、血清T−CHO値を図4及び表1に、解剖時の血清尿酸値を図5にそれぞれ示す。
LF群及びLF分解物群において、血清AST値、血清ALT値、血清TG値、血清T−CHO値がエタノール群と比較して低く、特にLF分解物群では血清ALT値、血清T−CHOが有意に低下した。
また、LF群及びLF分解物群において、血清尿酸値がエタノール群と比較して低く、特にLF分解物群では有意に低下した。
(6) Results (i) Biochemistry On days 14 and 28, serum AST values are shown in FIGS. 1 and 1, serum ALT values are shown in FIGS. 2 and 1, and serum TG values are shown in FIGS. 3 and 1. The T-CHO values are shown in FIGS. 4 and 1, and the serum uric acid levels at the time of dissection are shown in FIG. 5, respectively.
In the LF group and the LF degradation product group, the serum AST value, the serum ALT value, the serum TG value, and the serum T-CHO value are lower than those in the ethanol group. It decreased significantly.
Moreover, in the LF group and the LF decomposition product group, the serum uric acid level was lower than that in the ethanol group, and in particular, it was significantly decreased in the LF decomposition product group.
(ii)精巣重量
結果を図6に示す。
エタノール群においては、精巣重量が有意に減少するところ、LF群及びLF分解物群においては減少幅が小さかった。
(Ii) Testis weight The results are shown in FIG.
In the ethanol group, the testis weight was significantly reduced, but in the LF group and the LF degradation product group, the decrease was small.
(iv)肝臓鉄含量
結果を図7に示す。
エタノール群においては、肝臓の鉄含量が低値を示すところ、LF群及びLF分解物群においては減少幅が小さかった。
(Iv) Liver iron content The results are shown in FIG.
In the ethanol group, the iron content in the liver was low, but in the LF group and the LF decomposition product group, the decrease was small.
(v)病理組織学的検査
エタノール群においては、小葉中心性脂肪化及び小葉周辺性脂肪化が認められるところ、LF群及びLF分解物群においてはいずれの脂肪化を抑制する傾向が認められた。
(V) Histopathological examination In the ethanol group, central leaflet fattening and perilobular fattening were observed, but in the LF group and the LF degradation product group, both fattening tended to be suppressed. ..
(vi)アルコール代謝酵素の肝臓での発現
結果を図8及び9に示す。
LF群及びLF分解物群において、adh1及びaldh2がエタノール群と比較して有意に高く発現したことが認められた。
(Vi) The results of expression of alcohol-metabolizing enzyme in the liver are shown in FIGS. 8 and 9.
It was found that adh1 and aldh2 were significantly higher expressed in the LF group and the LF degradation product group than in the ethanol group.
<実施例2>ヒトのエタノール摂取後の呼気に含まれるエタノール、アセトアルデヒド濃度に対するラクトフェリンの影響の検討
(1)方法
健常成人に、蒸留水またはラクトフェリン600mgを蒸留水に溶解させた水溶液を50mL摂取させた。その30分後、10%エタノール水溶液を0.1g/Kg体重となるよう1分以内に摂取させ、更に40mLの蒸留水を口の中をすすぐように摂取させた。エタノール摂取60分後、90分後、及び120分後の呼気をセンサーガスクロマトグラフィーSEGA−P3−A(NISSHAエフアイエス株式会社)で分析し、呼気に含まれるエタノール濃度、及びアセトアルデヒド濃度をそれぞれ測定した。
<Example 2> Examination of the effect of lactoferrin on the concentrations of ethanol and acetaldehyde contained in exhaled breath after ingestion of human ethanol (1) Method A healthy adult is allowed to ingest 50 mL of distilled water or an aqueous solution of 600 mg of lactoferrin dissolved in distilled water. It was. Thirty minutes later, a 10% aqueous ethanol solution was ingested within 1 minute to a body weight of 0.1 g / Kg, and 40 mL of distilled water was ingested to rinse the mouth.
(2)結果
結果を図10及び11に示す。
LF水摂取群において、水摂取群と比較して、呼気に含まれるエタノール濃度、及びアセトアルデヒド濃度がともに低い値を示した。
(2) Results The results are shown in FIGS. 10 and 11.
In the LF water intake group, both the ethanol concentration and the acetaldehyde concentration contained in the exhaled breath were lower than those in the water intake group.
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JP2001247474A (en) * | 2000-03-07 | 2001-09-11 | Snow Brand Milk Prod Co Ltd | Medicine for preventing and/or treating liver disease |
WO2003057245A1 (en) * | 2001-12-28 | 2003-07-17 | Nrl Pharma, Inc. | Compositions for improving lipid metabolism |
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WO2003057245A1 (en) * | 2001-12-28 | 2003-07-17 | Nrl Pharma, Inc. | Compositions for improving lipid metabolism |
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