JP2019142976A - Adjuvant - Google Patents
Adjuvant Download PDFInfo
- Publication number
- JP2019142976A JP2019142976A JP2019104532A JP2019104532A JP2019142976A JP 2019142976 A JP2019142976 A JP 2019142976A JP 2019104532 A JP2019104532 A JP 2019104532A JP 2019104532 A JP2019104532 A JP 2019104532A JP 2019142976 A JP2019142976 A JP 2019142976A
- Authority
- JP
- Japan
- Prior art keywords
- vitamin
- lactoferrin
- immunostimulant
- acid
- present
- 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
Links
- 239000002671 adjuvant Substances 0.000 title abstract 3
- 102000010445 Lactoferrin Human genes 0.000 claims abstract description 58
- 108010063045 Lactoferrin Proteins 0.000 claims abstract description 58
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- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
Description
本発明は、免疫賦活剤に係り、詳しくは、ラクトフェリン及び特定の他の成分を有効成分とする免疫賦活剤に関する。 The present invention relates to an immunostimulant, and more particularly, to an immunostimulant containing lactoferrin and specific other components as active ingredients.
近年、ガン、エイズ、アレルギー等の免疫に関連する疾患が増加傾向にある。これらの疾患は、加齢、ストレス、疲労、環境因子などにより、免疫機能が低下した場合に引き起こされやすくなると考えられている。したがって、日頃から免疫力を強化することが望まれている。 In recent years, diseases related to immunity such as cancer, AIDS, and allergies have been increasing. These diseases are considered to be easily caused when immune function is lowered due to aging, stress, fatigue, environmental factors and the like. Therefore, it is desired to strengthen immunity on a daily basis.
免疫力を強化させる免疫賦活剤としては、例えば、多糖の基本構造の糖残基が少なくともガラクトースとマンノースで構成されており、当該ガラクトースにフラノース型が存在する多糖体を含有する免疫賦活剤（特許文献１参照）や、レンチナンと、特定のピロリドン類及びスルホキシド類から選ばれる１種以上とを組み合わせてなる免疫賦活剤（特許文献２参照）等が提案されている。 As an immunostimulant that enhances immunity, for example, an immunostimulant containing a polysaccharide in which the sugar residue of the basic structure of a polysaccharide is composed of at least galactose and mannose, and the galactose has a furanose type (patent Document 1), an immunostimulant (see Patent Document 2) that combines lentinan and at least one selected from specific pyrrolidones and sulfoxides have been proposed.
また、ラクトフェリンを有効成分とする免疫賦活剤も提案されている（特許文献３参照）。この文献においては、ラクトフェリンが、マクロファージではなく好中球に対して作用することが開示されており、その作用としては、好中球の貧食機能を向上させることが記載されている。 In addition, an immunostimulant containing lactoferrin as an active ingredient has also been proposed (see Patent Document 3). In this document, it is disclosed that lactoferrin acts on neutrophils, not macrophages, and as its action, it is described that the phagocytic function of neutrophils is improved.
本発明の課題は、マクロファージ活性化能が飛躍的に向上した免疫賦活剤を提供することにある。 The subject of this invention is providing the immunostimulant which macrophage activation ability improved dramatically.
本発明者らは、ラクトフェリンの免疫賦活作用について鋭意調査・研究したところ、ラクトフェリンと特定の他の成分とを組み合わせることにより、マクロファージ活性化能を飛躍的に向上させることができることを見いだし、本発明を完成するに至った。すなわち、ラクトフェリンと、マクロファージ活性化能がほとんどないか、その能力が小さい特定の他の成分を組み合わせることにより、マクロファージ活性化能を相乗的に向上させることができることを見いだした。 The present inventors diligently investigated and studied the immunostimulatory action of lactoferrin, and found that the ability to activate macrophages can be drastically improved by combining lactoferrin and specific other components. It came to complete. That is, it has been found that the ability to activate macrophages can be synergistically improved by combining lactoferrin with specific other components that have little or no ability to activate macrophages.
すなわち、本発明は、ラクトフェリンと、下記（ａ）〜（ｅ）からなる群より選ばれる少なくとも１種の成分とを有効成分として含有することを特徴とする免疫賦活剤に関する。
（ａ）甘藷、長命草、ヨモギ、松、葛、及びターミナリアから選ばれる少なくとも１種の植物素材
（ｂ）アスパルテーム、麦芽糖、ショ糖脂肪酸エステル、フラクトオリゴ糖、トレハロース、還元パラチノース、還元麦芽糖、及びシェラックから選ばれる少なくとも１種の機能性添加剤
（ｃ）アラニン、アルギニン、アスパラギン、アスパラギン酸、システイン、グルタミン、グルタミン酸、グリシン、ヒスチジン、イソロイシン、ロイシン、リジン、メチオニン、フェニルアラニン、プロリン、セリン、トレオニン、トリプトファン、チロシン、及びバリンから選ばれる少なくとも１種のアミノ酸
（ｄ）没食子酸及びクロロゲン酸から選ばれる少なくとも１種のポリフェノール
（ｅ）ビタミンＢ１、ビタミンＢ２、ビタミンＢ６、ビタミンＢ１２、ビタミンＣ、ビタミンＤ３、ビタミンＥ、パントテン酸ナトリウム、ナイアシン、葉酸、ビオチン、カルシウム、マンガン、亜鉛、鉄、銅、モリブデン、マグネシウム、及びクロムから選ばれる少なくとも１種のビタミン・ミネラル類
That is, the present invention relates to an immunostimulator comprising lactoferrin and at least one component selected from the group consisting of the following (a) to (e) as active ingredients.
(A) at least one plant material selected from sweet potato, long-life grass, mugwort, pine, kuzu and terminaria (b) aspartame, maltose, sucrose fatty acid ester, fructooligosaccharides, trehalose, reduced palatinose, reduced maltose, and shellac At least one functional additive selected from (c) alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan (D) At least one polyphenol selected from gallic acid and chlorogenic acid (e) Vitamin B1, vitamin B2, vitamin B6, vitamin At least one vitamin / mineral selected from vitamin B12, vitamin C, vitamin D3, vitamin E, sodium pantothenate, niacin, folic acid, biotin, calcium, manganese, zinc, iron, copper, molybdenum, magnesium, and chromium
本発明の免疫賦活剤は、ラクトフェリンと（ａ）〜（ｅ）からなる群より選ばれる少なくとも１種の成分とからなる有効成分を添加して得たものであってもよい。 The immunostimulant of the present invention may be obtained by adding an active ingredient consisting of lactoferrin and at least one component selected from the group consisting of (a) to (e).
本発明の免疫賦活剤において、ラクトフェリン及び他の有効成分の配合質量比は、０．５：１〜７０：１の範囲であることが好ましい。
また、本発明の免疫賦活剤は、錠剤、カプセル剤、粉末剤、顆粒剤、又は液剤であることが好ましい。
In the immunostimulant of the present invention, the blending mass ratio of lactoferrin and other active ingredients is preferably in the range of 0.5: 1 to 70: 1.
The immunostimulant of the present invention is preferably a tablet, capsule, powder, granule, or liquid.
また、本発明は、上記本発明の免疫賦活剤を摂取させることを特徴とする免疫賦活方法（ただし、医療行為を除く）に関する。 The present invention also relates to an immunostimulation method (excluding medical practice) characterized by ingesting the immunostimulant of the present invention.
本発明の免疫賦活剤は、マクロファージ活性化能を飛躍的に向上させることができる。 The immunostimulant of the present invention can dramatically improve the macrophage activation ability.
本発明の免疫賦活剤は、ラクトフェリンと、下記（ａ）〜（ｅ）からなる群より選ばれる少なくとも１種の成分（以下、他成分ということがある）とを有効成分として含有することを特徴とする。すなわち、ラクトフェリンと共に用いられる下記（ａ）〜（ｅ）の成分は、１種（例えば（ａ）成分）であってもよいし、２種以上組み合わせてもよい。他成分を２種以上組み合せて用いる場合、ラクトフェリンと相乗効果の高い他成分同士を組み合わせることが好ましい。本発明の免疫賦活剤は、高いマクロファージ活性化能を有し、免疫を高めることができる。 The immunostimulant of the present invention contains lactoferrin and at least one component selected from the group consisting of the following (a) to (e) (hereinafter sometimes referred to as other components) as active components. And That is, the following components (a) to (e) used together with lactoferrin may be one type (for example, component (a)), or two or more types may be combined. When using 2 or more types of other components in combination, it is preferable to combine lactoferrin and other components having a high synergistic effect. The immunostimulant of the present invention has high macrophage activation ability and can enhance immunity.
［ラクトフェリン］
本発明の免疫賦活剤の有効成分となるラクトフェリンとしては、例えば、哺乳類の乳等の分泌液から分離されるラクトフェリンを挙げることができる。具体的には、ウシ、ヒト等の哺乳動物の乳や、これらの乳を加工して得られる脱脂乳、ホエイ（乳清）等から分離精製したものを例示することができる。ラクトフェリンは、医薬品、試薬等として市販されており、これらの市販品を用いることができる。
[Lactoferrin]
As a lactoferrin used as the active ingredient of the immunostimulant of this invention, the lactoferrin isolate | separated from secretions, such as mammalian milk, can be mentioned, for example. Specific examples include milk separated from milk from mammals such as cows and humans, skim milk obtained by processing these milks, whey (whey), and the like. Lactoferrin is commercially available as pharmaceuticals, reagents and the like, and these commercially available products can be used.
［他成分］ [Other ingredients]
（ａ）植物素材
本発明の免疫賦活剤においては、ラクトフェリンと共に、有効成分として、甘藷、長命草、ヨモギ、松、葛、及びターミナリアから選ばれる少なくとも１種の植物素材を用いることが好ましい。
(A) Plant Material In the immunostimulant of the present invention, it is preferable to use at least one plant material selected from sweet potato, long life grass, mugwort, pine, kuzu, and terminia as an active ingredient together with lactoferrin.
これらの植物素材は、葉、茎、根、花、実、幹、枝等、植物のいずれの部位であってもよく、植物素材そのもの（乾燥物を含む）の他、その粉砕物、搾汁、抽出物等の植物素材処理物を用いることができる。粉砕物としては、粉末、顆粒等が挙げられる。絞汁や抽出物は、液状であってもよいが、ペースト状や乾燥粉末として用いることもできる。抽出物は、適当な溶媒を用いて抽出することに得ることができ、溶媒としては、例えば、水（熱水）、エタノール、含水エタノールを用いることができる。これらの植物素材は、市販されているものを使用することができる。 These plant materials may be any part of the plant such as leaves, stems, roots, flowers, fruits, trunks, branches, etc. In addition to the plant materials themselves (including dried products), pulverized products, juices In addition, a processed plant material such as an extract can be used. Examples of the pulverized product include powder and granules. The juice or extract may be liquid, but can also be used as a paste or dry powder. The extract can be obtained by extraction using an appropriate solvent. As the solvent, for example, water (hot water), ethanol, or hydrous ethanol can be used. As these plant materials, commercially available products can be used.
甘藷とは、ヒルガオ科に属する植物をいい、一般にサツマイモと呼ばれる。甘藷の品種は、特に限定されるものではなく、例えば、すいおう、ジョイホワイト、コガネセンガン、シロユタカ、サツマスターチ、アヤムラサキ等を挙げることができる。本発明の植物素材として用いる部位としては、茎、葉が好ましく、特に若葉が好ましい。 Sweet potato is a plant belonging to the convolvulaceae family and is generally called sweet potato. The sweet potato varieties are not particularly limited, and examples include suiou, joy white, koganesengan, white yutaka, sweet potato, and ayamurasaki. As a site | part used as a plant raw material of this invention, a stem and a leaf are preferable and especially a young leaf is preferable.
長命草は、セリ科カワラボウフウ属に属するボタンボウフウとも呼ばれる多年草植物である。本発明の植物素材として用いる部位としては、葉、根が好ましい。 Long-life grass is a perennial plant that is also referred to as a button-bowl, which belongs to the genus Azalea. As a site | part used as a plant raw material of this invention, a leaf and a root are preferable.
ヨモギは、キク科の多年草である。本発明の植物素材として用いる部位としては、茎、葉が好ましい。 Mugwort is a perennial plant belonging to the family Asteraceae. As a site | part used as a plant raw material of this invention, a stem and a leaf are preferable.
松としては、例えば、フランス海岸松（Ｐｉｎｕｓ Ｍａｒｔｉｍａ）、カラマツ、クロマツ、アカマツ等を挙げることができ、これらの中でも、プロアントシアニジンが豊富に含まれるフランス海岸松（Ｐｉｎｕｓ Ｍａｒｔｉｍａ）が好ましい。本発明の植物素材として用いる部位としては樹皮が好ましく、この松樹皮から得られる抽出物が特に好ましい。この抽出物には、プロアントシアニジンの他、オリゴメリックプロアントシアニジンが高濃度で含まれており、例えば、抽出物の乾燥質量に対してオリゴメリックプロアントシアニジンを２０質量％以上含むものが好ましい。 Examples of the pine include French coastal pine (Pinus Martina), larch, black pine, Japanese red pine, etc. Among them, French coastal pine (Pinus Martina) rich in proanthocyanidins is preferable. The bark is preferred as the site used as the plant material of the present invention, and an extract obtained from this pine bark is particularly preferred. This extract contains a high concentration of oligomeric proanthocyanidins in addition to proanthocyanidins. For example, it is preferable that the extract contains 20% by mass or more of oligomeric proanthocyanidins with respect to the dry mass of the extract.
葛は、マメ科クズ属のつる性の多年草植物である。本発明の植物素材として用いる部位としては、花、根が好ましく、花が特に好ましい。葛花としては、蕾から全開した花までのいずれの過程で採取したものを用いてもよく、各過程で採取したものを混合して用いることもできる。葛の種類としては、特に制限はないが、プエラリア・トムソニイ（Pueraria thomsonii）、プエラリア・ロバータ（Pueraria lobata）、プエラリア・スンバーギアナ（Pueraria thunbergiana）等を例示することができる。 Kuzu is a perennial plant of the leguminous genus Kudzu. As a site | part used as a plant raw material of this invention, a flower and a root are preferable and a flower is especially preferable. As Kuzuhana, what was collected in any process from the bud to the fully-opened flower may be used, and what was collected in each process can also be mixed and used. The type of kuzu is not particularly limited, and examples thereof include Pueraria thomsonii, Pueraria lobata, Pueraria thunbergiana and the like.
ターミナリアとしては、例えば、Terminalia bellirica（belerica）、Terminalia catappa、Terminalia tomentosa、Terminalia citrina、Terminalia phellocarpa、Terminalia copelandii、Terminalia brassi、Terminalia ivorensis、Terminalia superba、Terminalia arjuna、Terminalia chebula等を挙げることができ、これらの中でも、Terminalia bellirica（belerica）、Terminalia chebulaが好ましい。本発明の植物素材として用いる部位としては、果実が好ましい。 Examples of terminaria include Terminalia bellirica (belerica), Terminalia catappa, Terminalia tomentosa, Terminalia citrina, Terminalia phellocarpa, Terminalia copelandii, Terminalia brassi, Terminalia ivorensis, Terminalia superba, Terminalia arjuna, Terminalia chebula, etc. Among these, Terminalia bellirica (belerica) and Terminalia chebula are preferable. As a part used as a plant material of the present invention, a fruit is preferable.
（ｂ）機能性添加剤
本発明の免疫賦活剤においては、ラクトフェリンと共に、有効成分として、アスパルテーム、麦芽糖、ショ糖脂肪酸エステル、フラクトオリゴ糖、トレハロース、還元パラチノース、還元麦芽糖、及びシェラックから選ばれる少なくとも１種の機能性添加剤を用いることが好ましい。アスパルテーム、ショ糖脂肪酸エステル、フラクトオリゴ糖、還元パラチノース、還元麦芽糖、及びシェラックは、単独ではマクロファージ活性化能がないにもかかわらず、ラクトフェリンと組み合わせることで、ラクトフェリン単独の場合に比して、マクロファージ活性化能を向上させることができる。なお、アスパルテーム、麦芽糖、フラクトオリゴ糖、トレハロース、還元パラチノース、還元麦芽糖等は、甘味料としても機能することから、本発明の免疫賦活剤に甘みを付与することができる。
(B) Functional additive In the immunostimulant of the present invention, at least one selected from aspartame, maltose, sucrose fatty acid ester, fructooligosaccharide, trehalose, reduced palatinose, reduced maltose, and shellac as an active ingredient together with lactoferrin. It is preferred to use seed functional additives. Aspartame, sucrose fatty acid ester, fructooligosaccharide, reduced palatinose, reduced maltose, and shellac are not capable of activating macrophages alone, but in combination with lactoferrin, compared to lactoferrin alone, macrophage activity The ability to improve can be improved. In addition, since aspartame, maltose, fructooligosaccharide, trehalose, reduced palatinose, reduced maltose and the like also function as a sweetener, it is possible to impart sweetness to the immunostimulant of the present invention.
（ｃ）アミノ酸
本発明の免疫賦活剤においては、ラクトフェリンと共に、有効成分として、アラニン、アルギニン、アスパラギン、アスパラギン酸、システイン、グルタミン、グルタミン酸、グリシン、ヒスチジン、イソロイシン、ロイシン、リジン、メチオニン、フェニルアラニン、プロリン、セリン、トレオニン、トリプトファン、チロシン、及びバリンから選ばれる少なくとも１種のアミノ酸（塩を含む）を用いることが好ましい。塩としては、例えば、ナトリウム塩、塩酸塩等を挙げることができる。
(C) Amino acid In the immunostimulant of the present invention, together with lactoferrin, as active ingredients, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, lysine, lysine, methionine, phenylalanine, proline , Serine, threonine, tryptophan, tyrosine, and at least one amino acid (including salt) selected from valine is preferably used. Examples of the salt include sodium salt and hydrochloride.
（ｄ）ポリフェノール
本発明の免疫賦活剤においては、ラクトフェリンと共に、有効成分として、没食子酸及びクロロゲン酸から選ばれる少なくとも１種のポリフェノールを用いることが好ましい。
(D) Polyphenol In the immunostimulant of the present invention, it is preferable to use at least one polyphenol selected from gallic acid and chlorogenic acid as an active ingredient together with lactoferrin.
（ｅ）ビタミン・ミネラル類
本発明の免疫賦活剤においては、ラクトフェリンと共に、有効成分として、ビタミンＢ１、ビタミンＢ２、ビタミンＢ６、ビタミンＢ１２、ビタミンＣ、ビタミンＤ３、ビタミンＥ、パントテン酸ナトリウム、ナイアシン、葉酸、ビオチン、カルシウム、マンガン、亜鉛、鉄、銅、モリブデン、マグネシウム、及びクロムから選ばれる少なくとも１種のビタミン・ミネラル類を用いることが好ましい。なお、本発明のミネラル類としてのカルシウム、マンガン、亜鉛、鉄、銅、モリブデン、マグネシウム、及びクロムは、これらの金属を含む化合物の形態を含む。
(E) Vitamins and minerals In the immunostimulant of the present invention, lactoferrin, as an active ingredient, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D3, vitamin E, sodium pantothenate, niacin, It is preferable to use at least one vitamin / mineral selected from folic acid, biotin, calcium, manganese, zinc, iron, copper, molybdenum, magnesium, and chromium. In addition, calcium, manganese, zinc, iron, copper, molybdenum, magnesium, and chromium as the minerals of the present invention include forms of compounds containing these metals.
本発明の免疫賦活剤は、ラクトフェリン及び所定の他成分を含有し、免疫賦活に用いられる点において、製品として他の製品と区別することができるものであれば特に制限されるものではなく、例えば、本発明に係る製品の本体、包装、説明書、宣伝物のいずれかに免疫賦活作用（マクロファージ活性化）の機能がある旨を表示したものが本発明の範囲に含まれる。例えば、医薬品（医薬部外品を含む）や、特定保健用食品、栄養機能食品、機能性表示食品等の所定機関より効能の表示が認められた機能性食品などのいわゆる健康食品や、飼料等を挙げることができる。いわゆる健康食品においては、「健康な生活習慣を目ざす」、「すこやかな毎日に」、「健康な体を維持したい人に」、「戦う力を補う」、「外敵に負けない」、「健康なカラダをサポート」等を表示したものを例示することができる。本発明の免疫賦活剤は、性別や年齢に関係なく摂取することができるが、本発明の免疫賦活剤の効果をより有効に享受することができることから、女性が摂取することが望ましく、閉経後の女性が摂取することがより望ましい。 The immunostimulant of the present invention is not particularly limited as long as it contains lactoferrin and other predetermined components and can be distinguished from other products as a product in terms of being used for immunostimulation. Any of the main body, packaging, instructions, and promotional material of the product according to the present invention indicating that it has an immunostimulating function (macrophage activation) is included in the scope of the present invention. For example, so-called health foods such as pharmaceuticals (including quasi-drugs), functional foods for which the indication of efficacy has been approved by specified organizations such as foods for specified health use, functional nutritional foods, functional foods, etc. Can be mentioned. In so-called health foods, "Aiming for healthy lifestyles", "For healthy life", "For those who want to maintain a healthy body", "Supplementing the power to fight", "Do not lose to external enemies", "Healthy For example, “support body” can be displayed. The immunostimulant of the present invention can be taken regardless of gender and age, but since it can enjoy the effect of the immunostimulant of the present invention more effectively, it is desirable for women to take it, and It is more desirable for women to take.
本発明の免疫賦活剤の形態としては、例えば、錠剤、カプセル剤、粉末剤、顆粒剤、液剤、粒状剤、棒状剤、板状剤、ブロック状剤、固形状剤、丸状剤、ペースト状剤、クリーム状剤、カプレット状剤、ゲル状剤、チュアブル状剤、スティック状剤等を挙げることができる。これらの中でも、錠剤、カプセル剤、粉末剤、顆粒剤、液剤の形態が特に好ましい。具体的には、サプリメントや、ペットボトル、缶、瓶等に充填された容器詰飲料や、水（湯）、牛乳、果汁、青汁等に溶解して飲むためのインスタント粉末飲料、インスタント顆粒飲料を例示することができる。これらは食事の際などに手軽に飲用しやすく、また嗜好性を高めることができるという点で好ましい。 Examples of the form of the immunostimulant of the present invention include tablets, capsules, powders, granules, liquids, granules, rods, plates, block agents, solid agents, round agents, and pastes. Agents, cream agents, caplet agents, gel agents, chewable agents, stick agents and the like. Among these, the forms of tablets, capsules, powders, granules, and liquids are particularly preferable. Specifically, supplements, container-packed beverages filled in PET bottles, cans, bottles, etc., instant powder beverages and instant granule beverages for dissolving and drinking in water (hot water), milk, fruit juice, green juice, etc. Can be illustrated. These are preferable in that they can be easily taken at the time of eating and the like, and can enhance palatability.
本発明の免疫賦活剤におけるラクトフェリン及び他成分（有効成分）の含有量としては、その効果の奏する範囲で適宜含有させればよい。 What is necessary is just to contain suitably in the range with the effect as content of the lactoferrin and other components (active ingredient) in the immunostimulant of this invention.
一般的には、本発明の免疫賦活剤が医薬品やサプリメント（錠剤，カプセル剤）の場合には、有効成分が乾燥質量換算で全体の０．０１〜１００質量％含まれていることが好ましく、０．１〜８５質量％含まれていることがより好ましく、０．５〜７０質量％含まれていることがさらに好ましい。 In general, when the immunostimulant of the present invention is a pharmaceutical or a supplement (tablet, capsule), it is preferable that the active ingredient is contained in an amount of 0.01 to 100% by mass in terms of dry mass, It is more preferable that 0.1-85 mass% is contained, and it is further more preferable that 0.5-70 mass% is contained.
本発明の免疫賦活剤が容器詰飲料（液剤）である場合には、有効成分が乾燥質量換算で全体の０．０１〜１０質量％含まれていることが好ましく、０．０３〜６質量％含まれていることがより好ましく、０．０５〜４質量％含まれていることがさらに好ましい。 When the immunostimulant of the present invention is a packaged beverage (liquid), the active ingredient is preferably contained in an amount of 0.01 to 10% by mass in terms of dry mass, and 0.03 to 6% by mass. More preferably, it is more preferably contained in an amount of 0.05 to 4% by mass.
また、本発明の免疫賦活剤がインスタント粉末飲料（粉末剤）、インスタント顆粒飲料（顆粒剤）である場合には、有効成分が乾燥質量換算で全体の１〜１００質量％含まれていることが好ましく、５〜９０質量％含まれていることがより好ましく、１０〜８０質量％含まれていることがさらに好ましい。 Moreover, when the immunostimulant of this invention is an instant powder drink (powder) and an instant granule drink (granule), the active ingredient may contain 1-100 mass% of the whole in dry mass conversion. Preferably, 5 to 90% by mass is contained, and 10 to 80% by mass is more preferred.
本発明の効果をより有効に発揮させるためには、有効成分が乾燥質量換算で本発明の免疫賦活剤全体（水分を除く）の８０質量％以上含まれていることが好ましく、９０質量％以上含まれていることがより好ましく、９５質量％以上含まれていることがさらに好ましく、１００質量％であることが特に好ましい。さらに、本発明の免疫賦活剤が成分（ａ）〜（ｅ）のいずれかを含有する場合、その含有される成分は、本発明における有効成分のみで構成されることが好ましい。すなわち、本発明の免疫賦活剤が例えば成分（ａ）（植物素材）を含む場合には、甘藷、長命草、ヨモギ、松、葛、ターミナリア以外の植物素材を含まないように構成することが好ましい。 In order to exhibit the effect of the present invention more effectively, the active ingredient is preferably contained in an amount of 80% by mass or more of the entire immunostimulant of the present invention (excluding moisture) in terms of dry mass, and 90% by mass or more. It is more preferably contained, more preferably 95% by mass or more, and particularly preferably 100% by mass. Furthermore, when the immunostimulant of this invention contains any of component (a)-(e), it is preferable that the component contained is comprised only with the active ingredient in this invention. That is, when the immunostimulant of the present invention contains, for example, the component (a) (plant material), it is preferable that it is configured not to contain plant materials other than sweet potato, long life grass, mugwort, pine, kuzu, and terminaria. .
本発明の免疫賦活剤の摂取量としては特に制限はないが、本発明の効果をより顕著に発揮させる観点から、１日当たりの有効成分の摂取量が、５０ｍｇ／日以上となるように摂取することが好ましく、１００ｍｇ／日以上となるように摂取することがより好ましく、３００ｍｇ／日以上となるように摂取することがさらに好ましい。その上限は特に制限されないが、例えば、８ｇ／日であり、好ましくは４ｇ／日である。本発明の免疫賦活剤は、1日の摂取量が前記摂取量となるように、１つの容器に、又は例えば２〜３の複数の容器に分けて、1日分として収容することができる。 Although there is no restriction | limiting in particular as an intake of the immunostimulant of this invention, It ingests so that the intake of the active ingredient per day may be 50 mg / day or more from a viewpoint of exhibiting the effect of this invention more notably. It is preferable to ingest it so that it may be 100 mg / day or more, and it is still more preferable to ingest it so that it may become 300 mg / day or more. The upper limit is not particularly limited, but is, for example, 8 g / day, preferably 4 g / day. The immunostimulant of the present invention can be stored in one container or divided into a plurality of containers, for example, as one day so that the daily intake becomes the above intake.
ラクトフェリン及び他成分の配合質量比としては、乾燥質量換算で、０．５：１〜７０：１の範囲であることが好ましく、０．７５：１〜６０：１の範囲であることがより好ましく、１：１〜６０：１の範囲であることがさらに好ましく、１：１〜５０：１の範囲であることが特に好ましい。ラクトフェリン及び他成分の配合比が、上記範囲であることにより、本発明の効果をより有効に発揮することができる。 The blending mass ratio of lactoferrin and other components is preferably in the range of 0.5: 1 to 70: 1, more preferably in the range of 0.75: 1 to 60: 1, in terms of dry mass. The range of 1: 1 to 60: 1 is more preferable, and the range of 1: 1 to 50: 1 is particularly preferable. When the blending ratio of lactoferrin and other components is within the above range, the effects of the present invention can be more effectively exhibited.
本発明の免疫賦活剤は、必要に応じて、経口用として許容される添加剤や、有効成分以外の成分を添加して、公知の製剤方法によって製造することができる。 The immunostimulant of this invention can be manufactured by a well-known formulation method, adding the additive accept | permitted for oral use, and components other than an active ingredient as needed.
また、本発明の免疫賦活剤としては、有効成分を含有する免疫賦活用食品の他、食品に対して有効成分を添加して得た免疫賦活用食品を挙げることができ、例えば、通常の食品（天然の食品を含む）に比して本発明の有効成分含有量を増加させた食品や、本発明の有効成分を通常含まない食品に対して有効成分を添加した食品を挙げることができる。有効成分の添加は、それぞれの成分を別々に添加してもよいし、同時に添加してもよく、また、有効成分以外の他の成分と共に添加してもよい。 In addition to the immunostimulatory food containing the active ingredient, the immunostimulatory agent of the present invention can include an immunostimulatory food obtained by adding an active ingredient to the food. For example, a normal food Examples include foods in which the content of the active ingredient of the present invention is increased compared to (including natural foods) and foods in which the active ingredient is added to foods that do not normally contain the active ingredient of the present invention. For the addition of the active ingredients, the respective ingredients may be added separately, may be added simultaneously, or may be added together with other ingredients other than the active ingredients.
本発明の免疫賦活用食品としては、例えば、炭酸飲料、栄養飲料、果実飲料、乳酸飲料、スムージー、青汁等の飲料；アイスクリーム、アイスシャーベット、かき氷等の冷菓；そば、うどん、はるさめ、中華麺、即席麺等の麺類；飴、キャンディー、ガム、チョコレート、錠菓、スナック菓子、ビスケット、ゼリー、ジャム、クリーム、焼き菓子、パン等の菓子類；かまぼこ、ハム、ソーセージ等の水産・畜産加工食品；加工乳、発酵乳、ヨーグルト等の乳製品；サラダ油、てんぷら油、マーガリン、マヨネーズ、ショートニング、ホイップクリーム、ドレッシング等の油脂及びその加工食品；ソース、醤油等の調味料；カレー、シチュー、親子丼、お粥、雑炊、中華丼、かつ丼、天丼、牛丼、ハヤシライス、オムライス、おでん、マーボドーフ、餃子、シューマイ、ハンバーグ、ミートボール、各種ソース、各種スープ等のレトルトパウチ食品などを挙げることができる。 Examples of the immunostimulating food of the present invention include carbonated beverages, nutritional beverages, fruit beverages, lactic acid beverages, smoothies, green juices, and other frozen desserts such as ice cream, ice sherbet, shaved ice, soba, udon, harusame, and Chinese. Noodles such as noodles and instant noodles; sweets such as candy, candy, gum, chocolate, tablet confectionery, snack confectionery, biscuits, jelly, jam, cream, baked confectionery and bread; fishery and livestock processed foods such as kamaboko, ham and sausage Dairy products such as processed milk, fermented milk and yogurt; fats and processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing; seasonings such as sauces, soy sauce; curry, stew, oyakodon , Porridge, miscellaneous cooking, Chinese bowl, bonito, tempura bowl, beef bowl, hayashi rice, omelet rice, oden, marvod Off, dumplings, Shumai, hamburger, meatballs, various sources, such as retort pouch foods such as various types of soup can be mentioned.
本発明の免疫賦活方法としては、上記説明した本発明の免疫賦活剤を摂取させることを特徴とするが、医療行為は含まれない。本発明の免疫賦活剤は、性別や年齢に関係なく摂取することができるが、本発明の免疫賦活剤の効果をより有効に享受することができることから、女性に摂取させることが望ましく、閉経後の女性に摂取させることがより望ましい。本発明の方法としては、例えば、レストラン等の飲食店において、本発明の免疫賦活用食品を提供することにより、免疫の強化を図る方法を挙げることができる。 The immunostimulation method of the present invention is characterized by ingesting the immunostimulant of the present invention described above, but does not include medical practice. The immunostimulant of the present invention can be taken regardless of gender and age, but since the effect of the immunostimulant of the present invention can be enjoyed more effectively, it is desirable for women to take it, and It is more desirable to have females ingested. Examples of the method of the present invention include a method for enhancing immunity by providing the immunostimulating food of the present invention in a restaurant or the like.
以下、本発明を実施例に基づき説明する。
［実施例１］
１．細胞の培養
（１）３７℃、５％ＣＯ２インキュベーター内で、７５ｃｍ２フラスコを用いて、ＲＡＷ２６４．７細胞を１０％ＦＢＳ−ＤＭＥＭ（以下、培地）により培養した。
（２）トリプシン処理により浮遊させた細胞を、７５ｃｍ２フラスコから９６ｗｅｌｌ ｐｌａｔｅの各ｗｅｌｌに、２．５×１０４ｃｅｌｌｓ／ｗｅｌｌの細胞密度で播種した。
（３）３７℃、５％ＣＯ２インキュベーター内で４８時間前培養した。
（４）各ｗｅｌｌより培地を除去後、所定濃度に調製した被験物質含有培地を１００μＬずつ添加し、ＣＯ２インキュベーター内で２４時間培養した。なお、ラクトフェリンと他成分との併用サンプルについては、それぞれ２倍濃度の被験物質含有培地を調製し、５０μＬずつ添加することで目的の濃度とした。また、ｃｏｎｔｒｏｌについては、被験物質をＤＭＳＯに溶解したものに対しては０．２５％ＤＭＳＯ含有培地を用いた。
Hereinafter, the present invention will be described based on examples.
[Example 1]
1. Cell Culture (1) RAW264.7 cells were cultured in 10% FBS-DMEM (hereinafter referred to as medium) using a 75 cm 2 flask in a 37 ° C., 5% CO 2 incubator.
(2) Cells suspended by trypsin treatment were seeded from a 75 cm 2 flask to each well of 96 well plate at a cell density of 2.5 × 10 4 cells / well.
(3) Pre-culture for 48 hours in a 37 ° C., 5% CO 2 incubator.
(4) After removing the medium from each well, 100 μL each of the test substance-containing medium prepared to a predetermined concentration was added and cultured in a CO 2 incubator for 24 hours. In addition, about the combined sample of lactoferrin and another component, the test substance containing culture medium of 2 times concentration was prepared, respectively, and it was set as the target density | concentration by adding 50 microliters. For control, a medium containing 0.25% DMSO was used for the test substance dissolved in DMSO.
具体的に、被験物質培地の調製は、以下のように行った。
ラクトフェリンについては、１０％ＦＢＳ−ＤＭＥＭに溶解し、所定濃度（μｇ／ｍＬ）に調整した。
Specifically, the test substance medium was prepared as follows.
Lactoferrin was dissolved in 10% FBS-DMEM and adjusted to a predetermined concentration (μg / mL).
ラクトフェリンと共に用いる他成分としては、表１〜表５に示す物質を用いた。他成分については、基本的に、被検物質を１０％ＦＢＳ−ＤＭＥＭに溶解し、所定濃度（μｇ／ｍＬ）に調整した。ラクトフェリンとの併用サンプルは２倍濃度の被験物質含有培地を等量混合し、所定濃度とした。 As other components used with lactoferrin, substances shown in Tables 1 to 5 were used. For the other components, the test substance was basically dissolved in 10% FBS-DMEM and adjusted to a predetermined concentration (μg / mL). In the combined sample with lactoferrin, a test substance-containing medium having a double concentration was mixed in an equal amount to obtain a predetermined concentration.
ただし、黒ショウガ及びココナッツ（植物素材）、ショ糖脂肪酸エステル、シェラック及びステアリン酸カルシウム（機能性添加剤）、ビタミンＡ、ビタミンＥ、ビタミンＤ３及びビタミンＫ（ビタミン類）については、被検物質をＤＭＳＯに溶解し、ＤＭＳＯ終濃度が０．２５％になるよう所定濃度（μｇ／ｍＬ）に調整した。ラクトフェリンとの併用サンプルは２倍濃度の被験物質含有培地を等量混合し、所定濃度とした（ＤＭＳＯ終濃度０．２５％）。 However, for black ginger and coconut (plant material), sucrose fatty acid ester, shellac and calcium stearate (functional additive), vitamin A, vitamin E, vitamin D3 and vitamin K (vitamins), the test substance is DMSO And the final concentration of DMSO was adjusted to a predetermined concentration (μg / mL). In the combined sample with lactoferrin, an equal amount of a test substance-containing medium having a double concentration was mixed to obtain a predetermined concentration (DMSO final concentration 0.25%).
２．ＮＯ測定
（１）２４時間培養後、培養上清５０μＬを回収した。培養上清５０μＬにグリース試薬（２％リン酸、１％スルファニルアミド、０．１％Ｎ−１−ナフチルエチレンジアミン二塩酸塩）５０μＬを添加し、５５０ｎｍの吸光度（Ａ）を測定した。
また、ブランクとして被験物質含有培地５０μＬとグリース試薬５０μＬを反応後、５５０ｎｍの吸光度（Ｂ）を測定し、Ａ−Ｂを試料の吸光度として用いた。
（２）１０％ＦＢＳ−ＤＭＥＭにて調製した亜硝酸ナトリウム溶液で検量線を作成し、ＮＯ濃度（μＭ）を算出した。
（３）算出したＮＯ濃度を元に「％ ｏｆ ｃｏｎｔｒｏｌ」を算出した。
「％ ｏｆ ｃｏｎｔｒｏｌ」
＝試料のＮＯ濃度（μＭ）／ｃｏｎｔｒｏｌのＮＯ濃度（μＭ）×１００
2. NO measurement (1) After 24 hours of culture, 50 μL of the culture supernatant was collected. 50 μL of grease reagent (2% phosphoric acid, 1% sulfanilamide, 0.1% N-1-naphthylethylenediamine dihydrochloride) was added to 50 μL of the culture supernatant, and the absorbance (A) at 550 nm was measured.
Further, after reacting 50 μL of the test substance-containing medium and 50 μL of the grease reagent as a blank, the absorbance (B) at 550 nm was measured, and AB was used as the absorbance of the sample.
(2) A calibration curve was prepared with a sodium nitrite solution prepared with 10% FBS-DMEM, and the NO concentration (μM) was calculated.
(3) “% of control” was calculated based on the calculated NO concentration.
“% Of control”
= NO concentration of sample (μM) / NO concentration of control (μM) × 100
その結果を表１〜表５、及び図１〜図１５に示す。図中の各グラフは、左から、「コントロール（添加なし）」、「ラクトフェリン（ＬＦ）の単独添加」、「他成分の単独添加」、「ラクトフェリン＋他成分添加」の結果を表す。また、グラフ下部の説明における数値は、サンプル濃度を示し、例えば、図１の左のグラフの「ＬＦ_1000」は、ラクトフェリン１０００（μｇ／ｍＬ）を示す。添加成分の濃度単位は、すべてのグラフにおいて、μｇ／ｍＬである。なお、グラフの縦軸はＮＯ濃度の「％ ｏｆ ｃｏｎｔｒｏｌ」を表す。 The results are shown in Tables 1 to 5 and FIGS. Each graph in the figure represents the results of “control (no addition)”, “single addition of lactoferrin (LF)”, “single addition of other components”, and “addition of lactoferrin + other components” from the left. Moreover, the numerical value in description of the graph lower part shows sample concentration, for example, "LF_1000" of the left graph of FIG. 1 shows the lactoferrin 1000 (microgram / mL). The concentration unit of the additive component is μg / mL in all graphs. The vertical axis of the graph represents “% of control” of the NO concentration.
甘藷については、生若葉の微粉砕末を用いた。
長命草については、生葉の微粉砕末を用いた。
ヨモギについては、生葉の微粉砕末を用いた。
葛については、花の熱水抽出物（乾燥粉末）を用いた。
松については、フランス海岸松の樹皮の熱水抽出物（乾燥粉末）を用いた。
ターミナリアについては、果実の熱水抽出物（乾燥粉末）を用いた。
米ぬかについては、市販品を用いた。
マキベリーについては、市販品の果実の乾燥粉末を用いた。
For sweet potato, finely ground powder of fresh young leaves was used.
For long-life grass, finely ground powder of fresh leaves was used.
For mugwort, finely ground powder was used.
For kuzu, a hot water extract of flowers (dry powder) was used.
As for pine, a hot water extract (dry powder) of bark of French coastal pine was used.
For terminaria, fruit hot water extract (dry powder) was used.
About the rice bran, the commercial item was used.
For maqui berry, a commercially available fruit dry powder was used.
表１〜表５、及び図１〜図１５に示すように、ラクトフェリンと、特定の他成分を組み合わせることにより、マクロファージ活性化能を相乗的に向上させることができる。 As shown in Tables 1 to 5 and FIGS. 1 to 15, the ability to activate macrophages can be synergistically improved by combining lactoferrin and specific other components.
［実施例２］（錠剤の製造）
配合成分 組成(mg)
ラクトフェリン １００
甘藷若葉 ６０
フラクトオリゴ糖 ５０
ショ糖脂肪酸エステル ２０
シェラック １０
アラニン １０
没食子酸 １０
ビタミンＢ１ １０
塩化カルシウム １５
上記組成物を打錠し、錠剤を製造した。
[Example 2] (Manufacture of tablets)
Ingredients Composition (mg)
Lactoferrin 100
Gansu Wakaba 60
Fructooligosaccharide 50
Sucrose fatty acid ester 20
Shellac 10
Alanine 10
Gallic acid 10
Vitamin B1 10
Calcium chloride 15
The above composition was tableted to produce tablets.
［実施例３］（カプセル剤の製造）
配合成分 組成(mg)
ラクトフェリン ２００
長命草 ５０
麦芽糖 １０
フラクトオリゴ糖 ２０
アスパラギン １０
没食子酸 ５
ビタミンＣ ５
塩化鉄 ３
上記組成物をソフトカプセルに封入し、カプセル剤を製造した。
[Example 3] (Manufacture of capsules)
Ingredients Composition (mg)
Lactoferrin 200
Long Life Grass 50
Maltose 10
Fructooligosaccharide 20
Asparagine 10
Gallic acid 5
Vitamin C 5
Iron chloride 3
The above composition was enclosed in a soft capsule to produce a capsule.
［実施例４］（インスタント粉末剤の製造）
配合成分 組成(mg)
ラクトフェリン １０００
甘藷若葉 ２５０
長命草 １５０
ヨモギ １５０
松樹皮抽出物（乾燥粉末） ２．５
葛の花抽出物（乾燥粉末） １．０
ターミナリア １５０
アスパルテーム ５０
アラニン ５
没食子酸 １０
ビタミンＢ１ １０
塩化カルシウム １５
上記組成物を混合し、粉末剤を製造した。
[Example 4] (Production of instant powder)
Ingredients Composition (mg)
Lactoferrin 1000
Gansu Wakaba 250
Long Life Grass 150
Artemisia 150
Pine bark extract (dry powder) 2.5
Kuzu Flower Extract (Dry Powder) 1.0
Terminaria 150
Aspartame 50
Alanine 5
Gallic acid 10
Vitamin B1 10
Calcium chloride 15
The said composition was mixed and the powder agent was manufactured.
［実施例５］（ＰＥＴボトル液剤の製造）
配合成分 組成(mg)
ラクトフェリン ２０００
甘藷若葉 ２５
長命草 ２５
ヨモギ ２５
松樹皮抽出物（乾燥粉末） ０．５
葛の花抽出物（乾燥粉末） ０．２５
ターミナリア ２５
アスパルテーム ５０
アスパラギン酸 ５
クロロゲン酸 １０
ビタミンＣ ５
葉酸 １０
グルコン酸亜鉛 ０．１
水 ３５０ｍｌ
上記組成物をペットボトルに充填して密封し、液剤を製造した。
[Example 5] (Production of PET bottle liquid)
Ingredients Composition (mg)
Lactoferrin 2000
Gansu Wakaba 25
Long Life Grass 25
Artemisia 25
Pine bark extract (dry powder) 0.5
Kuzu Flower Extract (Dry Powder) 0.25
Terminaria 25
Aspartame 50
Aspartic acid 5
Chlorogenic acid 10
Vitamin C 5
Folic acid 10
Zinc gluconate 0.1
350 ml of water
The composition was filled in a plastic bottle and sealed to produce a liquid.
本発明の免疫賦活剤は、免疫を強化する効果を有し、経口剤として用いることができることから、本発明の産業上の有用性は高い。 Since the immunostimulant of the present invention has an effect of enhancing immunity and can be used as an oral agent, the industrial utility of the present invention is high.
Claims (1)
（ａ）甘藷、長命草、ヨモギ、松、葛、及びターミナリアから選ばれる少なくとも１種の植物素材
（ｂ）アスパルテーム、麦芽糖、ショ糖脂肪酸エステル、フラクトオリゴ糖、トレハロース、還元パラチノース、還元麦芽糖、及びシェラックから選ばれる少なくとも１種の機能性添加剤
（ｃ）アラニン、アルギニン、アスパラギン、アスパラギン酸、システイン、グルタミン、グルタミン酸、グリシン、ヒスチジン、イソロイシン、ロイシン、リジン、メチオニン、フェニルアラニン、プロリン、セリン、トレオニン、トリプトファン、チロシン、及びバリンから選ばれる少なくとも１種のアミノ酸
（ｄ）没食子酸及びクロロゲン酸から選ばれる少なくとも１種のポリフェノール
（ｅ）ビタミンＢ１、ビタミンＢ２、ビタミンＢ６、ビタミンＢ１２、ビタミンＣ、ビタミンＤ３、ビタミンＥ、パントテン酸ナトリウム、ナイアシン、葉酸、ビオチン、カルシウム、マンガン、亜鉛、鉄、銅、モリブデン、マグネシウム、及びクロムから選ばれる少なくとも１種のビタミン・ミネラル類 A health food comprising lactoferrin and at least one component selected from the group consisting of the following (a) to (e):
(A) at least one plant material selected from sweet potato, long-life grass, mugwort, pine, kuzu and terminaria (b) aspartame, maltose, sucrose fatty acid ester, fructooligosaccharides, trehalose, reduced palatinose, reduced maltose, and shellac At least one functional additive selected from (c) alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan (D) At least one polyphenol selected from gallic acid and chlorogenic acid (e) Vitamin B1, vitamin B2, vitamin B6, vitamin At least one vitamin / mineral selected from vitamin B12, vitamin C, vitamin D3, vitamin E, sodium pantothenate, niacin, folic acid, biotin, calcium, manganese, zinc, iron, copper, molybdenum, magnesium, and chromium
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