JP2012051811A - Immunoenhancing agent - Google Patents
Immunoenhancing agent Download PDFInfo
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- JP2012051811A JP2012051811A JP2010193205A JP2010193205A JP2012051811A JP 2012051811 A JP2012051811 A JP 2012051811A JP 2010193205 A JP2010193205 A JP 2010193205A JP 2010193205 A JP2010193205 A JP 2010193205A JP 2012051811 A JP2012051811 A JP 2012051811A
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- shogaol
- gingerol
- ginger extract
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- ginger
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Abstract
Description
本発明は6−ショウガオールを有効成分として含有する免疫増強剤に関する。 The present invention relates to an immune enhancer containing 6-shogaol as an active ingredient.
6−ショウガオール及び6−ジンゲロールはショウガ根茎及びその抽出物中に含まれる成分である。特許文献1によればショウガ根茎中の6−ショウガオール等のショウガオール類の含有量は、6−ジンゲロール等のジンゲロール類の含有量よりも小さい。
6-shogaol and 6-gingerol are components contained in ginger rhizome and its extract. According to
これらの成分に着目した技術として例えば以下の先行技術がある。
特許文献1には、これらの成分を含有するショウガ抽出物が体温上昇作用を奏することが記載されている。
For example, there are the following prior arts as techniques focusing on these components.
特許文献2にはショウガオール類を含有する糖尿病及び/又は肥満の治療予防剤が記載されている。具体的な実施形態として6−ショウガオールを0.005wt%(5.0mg%)含有する清涼飲料が開示されている。
特許文献3には、ジンゲロールとショウガオールを10:1〜1:10の重量濃度比で、合計0.001重量%以上含有し、香気成分であるar−クルクメンの含有量が15mg/kg以下であり、糖質の濃度が40〜90重量%であるショウガ加工食品組成物が記載されている。特許文献3では、健康機能性の優れたショウガオールの含有量を増大させるために、ショウガ抽出物等を加熱することが開示されている。
ショウガ抽出物を含有する飲料等は体を温める作用を有すると消費者に認識されている。 Beverages and the like containing ginger extract are recognized by consumers as having an action of warming the body.
しかしながら、ショウガ抽出物を含有する飲料等が免疫増強作用を奏するか否かは従来検討されていない。免疫増強作用を奏する組成物は、免疫力を維持することにより風邪をひき難くする効果を有すると期待される。 However, it has not been studied in the past whether or not beverages containing ginger extract have an immune enhancing effect. A composition that exerts an immune enhancing action is expected to have an effect of making it difficult to catch a cold by maintaining immunity.
そこで本発明はショウガの成分を有効成分とする免疫増強剤を提供することを目的とする。 Therefore, an object of the present invention is to provide an immunopotentiator comprising ginger components as active ingredients.
本発明者らは6−ショウガオールを含有するショウガ抽出物が免疫増強作用を奏することを見出し、本発明を完成させるに至った。本発明は以下の発明を包含する。
(1)6−ショウガオールを有効成分として含有する免疫増強剤。
(2)6−ショウガオールを、これを含有するショウガ抽出物の形態で含有する請求項1記載の免疫増強剤。
The present inventors have found that a ginger extract containing 6-shogaol has an immunopotentiating action, and has completed the present invention. The present invention includes the following inventions.
(1) An immune enhancer containing 6-shogaol as an active ingredient.
(2) The immune enhancer according to
(3)6−ショウガオールを、6−ショウガオールと6−ジンゲロールとを含有するショウガ抽出物の形態で含有し、
該ショウガ抽出物における6−ショウガオールの含有量が6−ジンゲロールの含有量に対して1.6倍以上である、
(2)の免疫増強剤。
(4)1日あたり0.01〜0.06mg/kg体重の6−ショウガオールがヒトに対して経口摂取されるように用いられる、(1)〜(3)のいずれかの免疫増強剤。
(3) containing 6-shogaol in the form of a ginger extract containing 6-shogaol and 6-gingerol,
The content of 6-shogaol in the ginger extract is 1.6 times or more with respect to the content of 6-gingerol.
(2) The immunopotentiator.
(4) The immunopotentiator according to any one of (1) to (3), which is used so that 0.01-0.06 mg / kg body weight of 6-shogaol per day is orally ingested by humans.
本発明によれば、6−ショウガオールを有効成分とする免疫増強剤が提供される。 According to the present invention, an immunopotentiator comprising 6-shogaol as an active ingredient is provided.
本発明の免疫増強剤の有効成分として用いられる6−ショウガオールは、これを含有するショウガ抽出物の形態のものであってもよいし、合成されたものであってもよいし、ショウガ等の植物に由来するものであってもよい。 6-shogaol used as an active ingredient of the immune enhancer of the present invention may be in the form of a ginger extract containing the same, or may be synthesized, such as ginger It may be derived from a plant.
6−ショウガオールは、好ましくは、ショウガ抽出物の形態、より好ましくは、6−ショウガオールと6−ジンゲロールとを含有するショウガ抽出物の形態で用いられる。特に好ましくは、6−ショウガオールの含有量が6−ジンゲロールの含有量に対して1.6倍以上であるショウガ抽出物の形態で用いられる。 6-shogaol is preferably used in the form of a ginger extract, more preferably in the form of a ginger extract containing 6-shogaol and 6-gingerol. Particularly preferably, it is used in the form of a ginger extract in which the content of 6-shogaol is 1.6 times or more the content of 6-gingerol.
ショウガ(Zingiber officinale)はショウガ目ショウガ科に属する。本発明で用いられるショウガ抽出物はショウガの根茎の抽出物を指す。 Ginger (Zingiber officinale) belongs to the family Ginger. The ginger extract used in the present invention refers to an extract of ginger rhizome.
ショウガの根茎における6−ショウガオールの含有量は、6−ジンゲロールの含有量よりも少ない。このため、通常の方法で調製されるショウガ抽出物中では6−ショウガオールの含有量が6−ジンゲロールの含有量に対して大幅に少なく、通常は6−ショウガオールの含有量は、6−ジンゲロールの含有量に対して1/5にも満たない。本発明者らは、ショウガ抽出物または抽出前のショウガ原料を加熱処理することにより6−ジンゲロールが減少し、6−ショウガオールが増加して、上記比率を満足するショウガ抽出物を得ることができることを見出した。 The content of 6-shogaol in the ginger rhizome is less than the content of 6-gingerol. For this reason, in the ginger extract prepared by the usual method, the content of 6-shogaol is significantly smaller than the content of 6-gingerol, and the content of 6-shogaol is usually 6-gingerol. It is less than 1/5 with respect to the content of. The present inventors can obtain a ginger extract satisfying the above ratio by reducing 6-gingerol and increasing 6-shogaol by heat-treating the ginger extract or the ginger raw material before extraction. I found.
6−ショウガオールの含有量が6−ジンゲロールの含有量に対して1.6倍以上、好ましくは2倍以上に高められたショウガ抽出物は、辛味を高めることなく免疫増強を達成することができるため好ましい。上記比率を実現するためには、ショウガ抽出物等を100〜130℃の温度で24〜60時間加熱処理することが好ましい。なお特許文献3の段落0015に開示されている条件(100℃以上、0.5〜5時間)での加熱処理では、加熱時間が短いために6−ショウガオールの含有量は6−ジンゲロールの含有量を超えることはできず、上記比率を達成することはできない。特許文献3の段落0023の実施例1に開示されている条件(115℃以上、2時間)での加熱処理では、6−ショウガオールの含有量は6−ジンゲロールの含有量に対して約0.47となる(段落0024)。
The ginger extract in which the content of 6-shogaol is increased to 1.6 times or more, preferably 2 times or more than the content of 6-gingerol, can achieve immune enhancement without increasing the pungency. Therefore, it is preferable. In order to achieve the above ratio, it is preferable to heat treat the ginger extract or the like at a temperature of 100 to 130 ° C. for 24 to 60 hours. In the heat treatment under the conditions (100 ° C. or higher, 0.5 to 5 hours) disclosed in paragraph 0015 of
ショウガ抽出物の調製において加熱処理を行う時点は特に限定されず、ショウガ抽出物を加熱処理してもよいし、抽出前のショウガ原料(例えば、ショウガ根茎を潰して得られるショウガ粉砕物や、ショウガ根茎を圧搾して得られるショウガ絞り汁)を加熱処理してもよい。 The time at which the heat treatment is performed in the preparation of the ginger extract is not particularly limited. You may heat-process the ginger juice obtained by pressing a rhizome.
ショウガ抽出物の調製のための抽出媒体は6−ショウガオール及び6−ジンゲロールを溶出可能なものであれば特に限定されず、典型的にはアセトン、低級アルコール、ヘキサン、酢酸エチル等の有機溶媒、超臨界二酸化炭素等の超臨界流体、が挙げられる。抽出は通常の方法により行うことができる。ショウガ抽出物の範囲には、ショウガ抽出物を分画して得られる6−ショウガオール及び6−ジンゲロールを含有するフラクションも包含される。 The extraction medium for the preparation of ginger extract is not particularly limited as long as it can elute 6-shogaol and 6-gingerol, and typically an organic solvent such as acetone, lower alcohol, hexane, ethyl acetate, And supercritical fluids such as supercritical carbon dioxide. The extraction can be performed by a usual method. The range of ginger extract also includes a fraction containing 6-shogaol and 6-gingerol obtained by fractionating ginger extract.
本発明の免疫増強剤は少量の摂取で効果を奏することができる。好ましくは、本発明の免疫増強剤は1日あたり0.01〜0.1mg/kg体重の6−ショウガオールがヒトに対して経口摂取されるように用いられる。免疫増強剤の経口摂取は数日間以上(例えば5日間以上)継続することが好ましい。 The immune enhancer of the present invention can be effective with a small amount of ingestion. Preferably, the immunopotentiator of the present invention is used so that 0.01-0.1 mg / kg body weight of 6-shogaol per day is taken orally to humans. Oral intake of the immunopotentiator is preferably continued for several days or more (for example, 5 days or more).
本発明の免疫増強剤はヒト等の哺乳動物において免疫力を高める作用だけでなく、ストレスによる免疫力の低下を抑制する作用を奏する。すなわち本発明の免疫増強剤の範囲には、免疫低下抑制剤も包含される。 The immunopotentiator of the present invention exhibits not only an effect of increasing immunity in mammals such as humans, but also an effect of suppressing a decrease in immunity due to stress. That is, the scope of the immune enhancer of the present invention includes an immune lowering suppressant.
本発明の免疫増強剤は飲食品組成物または医薬品組成物(医薬部外品組成物を含む。以下同じ)等の任意の形態であってよい。 The immune enhancer of the present invention may be in any form such as a food / beverage product composition or a pharmaceutical composition (including a quasi-drug composition; the same applies hereinafter).
飲食品組成物の形態としては、飲料、固形食品、半固形食品等が挙げられる。飲料としては、具体的には、果汁飲料、清涼飲料、アルコール飲料等が挙げられる。固形食品としては、例えば、飴、トローチ等を含む錠剤(タブレット)や糖衣錠の形態、顆粒の形態、粉末飲料、粉末スープ等の粉末の形態、ビスケット等のブロック菓子類の形態、カプセル、ゼリー等の形態等、種々の形態が挙げられる。半固形食品としては、例えばジャムのようなペーストの形態、チューイングガムのようなガムの形態が挙げられる。これらの飲食品組成物には6−ショウガオール、又は6−ショウガオールを含有するショウガ抽出物のほかに、本発明の所望の効果が損なわれない範囲で、飲食品原料として通常用いられる種々の成分を配合することができる。これらの成分は単独で、または組み合わされて使用され得る。 Examples of the form of the food / beverage product composition include beverages, solid foods and semi-solid foods. Specific examples of the beverage include fruit juice beverages, soft drinks, and alcoholic beverages. Examples of solid food include tablets (tablets) and sugar-coated tablets including candy, troches, etc., granules, powdered beverages, powdered soups, powdered blocks, confectionery such as biscuits, capsules, jelly, etc. There are various forms such as Examples of the semi-solid food include a paste form such as jam and a gum form such as chewing gum. In addition to the ginger extract containing 6-shogaol or 6-shogaol, these food and drink compositions are variously used as raw materials for food and drink as long as the desired effects of the present invention are not impaired. Ingredients can be blended. These components can be used alone or in combination.
飲食品組成物としては特に飲料の形態が好ましい。本発明の免疫増強剤が飲料の形態の場合、該飲料中の6−ショウガオールの含有量は1.0mg%以上であることが好ましく、1.5mg%以上であることがより好ましい。該飲料では、6−ショウガオールは、6−ショウガオールと6−ジンゲロールとを含有する、6−ショウガオールの含有量が6−ジンゲロールの含有量に対して1.6倍以上であるショウガ抽出物の形態で含有されることが好ましく、該飲料では更に、6−ショウガオールの含有量と6−ジンゲロールの含有量との合計が5.0mg%以下であることが好ましい。なお「mg%」とは、飲料100gあたりの質量(単位=mg)を指す。 As the food / beverage product composition, a beverage form is particularly preferable. When the immune enhancing agent of the present invention is in the form of a beverage, the content of 6-shogaol in the beverage is preferably 1.0 mg% or more, and more preferably 1.5 mg% or more. In the beverage, 6-shogaol contains 6-shogaol and 6-gingerol, and the content of 6-shogaol is 1.6 times or more than the content of 6-gingerol. In the beverage, the total content of 6-shogaol and 6-gingerol is preferably 5.0 mg% or less. Note that “mg%” refers to the mass (unit: mg) per 100 g of beverage.
飲料を調製するための他の成分としては例えば水、果糖ブドウ糖液糖、環状オリゴ糖、酸味料、増粘剤、イノシトール、香料、ナイアシン、酸化防止剤、ビタミン類、甘味料等が挙げられる。酸味料としては、クエン酸、リンゴ酸、グルコン酸、酒石酸、或いはこれらの塩等が挙げられる。増粘剤としては、ジェランガム、キサンタンガム、ペクチン、グアーガム、発酵セルロース等の増粘多糖類が挙げられる。甘味料としては、ショ糖、果糖、ブドウ糖、液糖等の糖類、はちみつ、スクラロース、アセスルファムカリウム、ソーマチン、アスパルテーム等の高甘味度甘味料が挙げられる。酸化防止剤としては、ビタミンC、酵素処理ルチン等が挙げられる。ビタミン類としては、ビタミンB1、ビタミンB6、ビタミンE等が挙げられる。これらの成分は単独で、または組み合わされて使用され得る。 Examples of other components for preparing a beverage include water, fructose glucose liquid sugar, cyclic oligosaccharide, acidulant, thickener, inositol, flavor, niacin, antioxidant, vitamins, sweetener and the like. Examples of the acidulant include citric acid, malic acid, gluconic acid, tartaric acid, and salts thereof. Examples of the thickener include thickening polysaccharides such as gellan gum, xanthan gum, pectin, guar gum, and fermented cellulose. Examples of the sweetener include sugars such as sucrose, fructose, glucose, and liquid sugar, and high sweetness sweeteners such as honey, sucralose, acesulfame potassium, thaumatin, and aspartame. Examples of the antioxidant include vitamin C and enzyme-treated rutin. Examples of vitamins include vitamin B 1 , vitamin B 6 , vitamin E and the like. These components can be used alone or in combination.
医薬品組成物としては種々の投与形態用に製剤化されたものを使用することができる。医薬品組成物の製剤形態は特に制限はなく、液剤、錠剤、顆粒剤、細粒、散剤、チュアブル剤等の経口剤、注射剤等の非経口剤等の通常の製剤形態が挙げられ、経口剤であることが好ましい。上記製剤は6−ショウガオールや6−ショウガオールを含有するショウガ抽出物と、賦形剤等の製薬上許容される他の成分とを使用して常法により調製することができる。 As the pharmaceutical composition, those formulated for various dosage forms can be used. There are no particular limitations on the formulation form of the pharmaceutical composition, and normal formulation forms such as oral preparations such as liquids, tablets, granules, fine granules, powders, chewable preparations, and parenteral preparations such as injections are included. It is preferable that The above preparation can be prepared by a conventional method using 6-shogaol or a ginger extract containing 6-shogaol and other pharmaceutically acceptable components such as excipients.
(検体)
実施例の液剤:ショウガ根茎の乾燥物より超臨界抽出法で得られた抽出物を120℃で48時間加熱して製造したショウガ抽出物(6−ショウガオール濃度:10質量%、6−ジンゲロール濃度:4.2質量%)をウェルソルブで希釈したもの。
対照検体:生理食塩水
(Sample)
Solution of Example: Ginger extract produced by heating an extract obtained from a dried ginger rhizome by supercritical extraction method at 120 ° C. for 48 hours (6-shogaol concentration: 10% by mass, 6-gingerol concentration) : 4.2% by mass) diluted with wellsolve.
Control sample: saline
(試験動物)
検疫馴化終了後に、体重を基に完全無作為化法で1群7匹のマウスを3群に群分け、後記の体温低下の測定試験を実施した。また、同様に群分けした別の3群のマウスについて後記のNK活性の測定試験を実施した。
(Test animal)
After the quarantine habituation was completed, 7 mice per group were divided into 3 groups by a completely randomized method based on body weight, and the measurement test for body temperature reduction described below was performed. In addition, the NK activity measurement test described below was performed on another three groups of mice that were similarly grouped.
(試験方法)
試験動物を次の3群に群分けした。
対照群:25℃の室内で5日間寒冷ストレスを負荷しない状態で生理食塩水を10ml/kg体重の割合で一日のはじめに5日間連続経口投与した群
実施例寒冷ストレス群:5℃の低温室内で5日間(1日目4時間、2日目7時間、3日目と4日目24時間、5日目10時間)飼育し寒冷ストレスを負荷する(1日目、2日目の他の時間は25℃の室内で飼育する)と共に、負荷期間中実施例の液剤を10ml/kg体重(ショウガ抽出物15mg/kg体重、6−ショウガオール1.5mg/kg体重が含まれる※)の割合で一日のはじめに5日間連続経口投与した群。この群の試験スケジュールを図3に模式的に示す。
対照寒冷ストレス群:前記と同様に寒冷ストレスを負荷すると共に、負荷期間中生理食塩水を10ml/kg体重の割合で一日のはじめに5日間連続経口投与した群
※6−ショウガオールの投与量の決定方法
6−ショウガオールのヒトへの投与量を1日あたり0.03 mg/kg体重(50kgのヒトに対する一日投与量が1.5mg)と設定した。ヒトでの投与量の有効性を、マウスを用いた試験により評価するために通常用いられる換算係数が50である。そこで、本試験では、ヒトでの投与量(1日あたり0.03 mg/kg体重)の有効性を評価するために、マウスへの1日あたりの投与量を1.5mg/kg体重(=0.03 mg/kg体重×50)とした。
(Test method)
The test animals were divided into the following three groups.
Control group: a group in which physiological saline was orally administered at a rate of 10 ml / kg body weight for 5 days in a room at 25 ° C. for 5 days without being subjected to cold stress. Example Cold stress group: cold room at 5 ° C. 5 days (4 hours on the first day, 7 hours on the second day, 24 hours on the third and fourth days, 10 hours on the fifth day) The time is kept indoors at 25 ° C.), and during the loading period, the ratio of 10 ml / kg body weight (including ginger extract 15 mg / kg body weight, 6-shogaol 1.5 mg / kg body weight *) Group administered orally for 5 consecutive days at the beginning of the day. The test schedule for this group is shown schematically in FIG.
Control cold stress group: A group in which cold stress was applied as described above, and physiological saline was orally administered at a rate of 10 ml / kg body weight for 5 consecutive days at the beginning of the day during the loading period. Determination method The dose of 6-shogaol to humans was set to 0.03 mg / kg body weight per day (the daily dose for a 50 kg human was 1.5 mg). The conversion factor normally used for evaluating the effectiveness of human doses in tests using mice is 50. Therefore, in this study, in order to evaluate the effectiveness of the human dose (0.03 mg / kg body weight per day), the daily dose to mice was 1.5 mg / kg body weight (= 0.03 mg / kg body weight × 50).
(体温低下の測定)
5日目検体投与時及び投与してから10時間後まで一定時間ごとにマウスの体温を体温計を肛門から挿入して腸内体温を測定することで求め、各群についてマウスの体温の平均値を測定した。
結果を表1及び図2に示す。
(Measurement of decreased body temperature)
The body temperature of the mouse was determined by inserting a thermometer through the anus and measuring the intestinal body temperature at the time of administration of the sample on the fifth day and every 10 hours after administration. It was measured.
The results are shown in Table 1 and FIG.
(NK(ナチュラル・キラー)活性の測定)
5日目4時間後各群のマウスより採血すると共に脾臓を無菌的に摘出して重量を測定した。摘出した脾臓よりリンパ球懸濁液を調製した。脾臓リンパ球懸濁液と蛍光標識したYAC−1細胞を混合・インキュベートし、FACSにより細胞障害性(%)を測定した。
結果を表2及び図2に示す。
(Measurement of NK (natural killer) activity)
Blood was collected from each group of
The results are shown in Table 2 and FIG.
Claims (4)
該ショウガ抽出物における6−ショウガオールの含有量が6−ジンゲロールの含有量に対して1.6倍以上である、
請求項2記載の免疫増強剤。 6-shogaol in the form of a ginger extract containing 6-shogaol and 6-gingerol,
The content of 6-shogaol in the ginger extract is 1.6 times or more with respect to the content of 6-gingerol.
The immunopotentiator according to claim 2.
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