JP6106543B2 - Appetite enhancement and / or weight gain inhibitor comprising β-eudesmol as an active ingredient - Google Patents
Appetite enhancement and / or weight gain inhibitor comprising β-eudesmol as an active ingredient Download PDFInfo
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- JP6106543B2 JP6106543B2 JP2013136959A JP2013136959A JP6106543B2 JP 6106543 B2 JP6106543 B2 JP 6106543B2 JP 2013136959 A JP2013136959 A JP 2013136959A JP 2013136959 A JP2013136959 A JP 2013136959A JP 6106543 B2 JP6106543 B2 JP 6106543B2
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- Prior art keywords
- eudesmol
- appetite
- active ingredient
- test
- weight gain
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Description
本発明は、β−ユーデスモールを有効成分として含有する食欲増進剤及び／又は体重増加抑制剤に関する。 The present invention relates to an appetite enhancer and / or weight gain inhibitor containing β-eudesmol as an active ingredient.
旧来より、ビールや、日本酒或いはワイン等の醸造酒は、食欲を増進する機能を有することが知られている。健全な健康を維持する上で、食欲は最も重要な因子であり、食欲が低下すると、体に栄養成分や機能成分の供給が衰えて、健常人の健全な健康機能を維持できないばかりでなく、生理機能の低下から各種の疾病を引き起こす要因ともなり得る。食欲不振は、ストレス等の環境要因に起因する場合や、体の生理機能の異常に起因する場合等、各種の要因があるが、従来より、食欲不振に対する対応策の一つとして、食欲増進剤の提供が検討されている。 Traditionally, brewed liquor such as beer, sake or wine has been known to have a function to increase appetite. Appetite is the most important factor in maintaining healthy health.If appetite declines, the supply of nutrients and functional ingredients to the body declines, not only failing to maintain healthy health functions of healthy people, It can be a factor causing various diseases due to a decrease in physiological function. There are various factors such as anorexia due to environmental factors such as stress, and abnormalities in the physiological functions of the body. Is being considered.
例えば、食欲増進剤としてグレリンが知られている（Nature,2001.Jan.11;409(6817):194-8.）。グレリンは、食欲増進ホルモンであり、胃底を裏打ちする上皮細胞により産生されて、食欲を刺激するように機能し、そのレベルは、食事の前に増加して、その後減少することが知られている（特表２０１２−７２１４４号公報）。また、胃液分泌を促進し、食欲を増進する食欲増進剤として、Ｎ−メチルチラミン、Ｎ，Ｎ−ジメチルチラミン、或いは、酵母発酵産物のガストリン分泌促進活性を有する画分を有効成分とする食欲増進剤が開示されている（特開平１１−１５８０６４号公報）。Ｎ−メチルチラミンは、ビール等の発酵産物や、麦芽等に含まれ、Ｎ，Ｎ−ジメチルチラミンは、大麦胚芽に含まれていることが知られており、該物質は、胃の幽門前庭部から分泌され、胃酸分泌促進作用を持つ消化管ホルモンであるガストリン分泌促進作用を有し、食欲増進作用を有する。 For example, ghrelin is known as an appetite enhancer (Nature, 2001. Jan. 11; 409 (6817): 194-8.). Ghrelin is an appetite-enhancing hormone, produced by epithelial cells lining the fundus, functions to stimulate appetite, and its levels are known to increase before eating and then decrease (Special Table 2012-72144). Furthermore, as an appetite enhancer that promotes gastric secretion and enhances appetite, N-methyltyramine, N, N-dimethyltyramine, or an appetite enhancer containing a yeast fermentation product fraction that has a gastrin secretion promoting activity as an active ingredient An agent is disclosed (Japanese Patent Laid-Open No. 11-1558064). It is known that N-methyltyramine is contained in fermented products such as beer and malt, and N, N-dimethyltyramine is known to be contained in barley germ. It is secreted from the stomach and has a gastrin secretion promoting action, which is a gastrointestinal hormone having a gastric acid secretion promoting action, and has an appetite promoting action.
また、特開２０１１−１４０４７７号公報には、ホップ中から単離した、キサントフモール、イソキサントフモール、８−プレニルナリンゲニンが、視床下部における食欲の調節に関与することが知られているＣＢ１受容体結合活性を有し、食欲を増進する作用を示すことが見出されたことから、該物質を有効成分とする食欲増進剤が開示されている。更に、ＷＯ２００６／０５４６４１には、ニューロペプチド（ＮＰＢ）のアナログであるペプチド誘導体が、摂食障害等への関連が知られているＧ蛋白受容体７（ＧＰＲ７）の選択的なリガンドであり、食欲増進剤として作用することが開示されている。 JP 2011-140477 A discloses CB1 that xanthohumol, isoxanthohumol, and 8-prenylnaringenin isolated from hops are involved in the regulation of appetite in the hypothalamus. Since it has been found that it has a receptor binding activity and exhibits an action of promoting appetite, an appetite enhancer containing the substance as an active ingredient has been disclosed. Furthermore, WO 2006/054641 discloses that a peptide derivative that is an analog of neuropeptide (NPB) is a selective ligand of G protein receptor 7 (GPR7) that is known to be associated with eating disorders and the like. It is disclosed to act as an enhancer.
これらの食欲増進剤は、その投与により、摂食量の増加をもたらすとされ、摂食障害の治療や、健常人においても食欲不振の症状緩和などに有効であるとされている。一方で、これら従来の食欲増進剤による摂食量の増加は、体重増加をもたらすことが報告されている（ＷＯ０１／３２１８２）。このことは、従来の食欲増進剤の使用は医師の指導管理のもとでの適切な使用が必要であり、摂食量増加による過剰な体重増加を引き起こし肥満やそれに起因する生活習慣病を引き起こすリスクをも同時に有しているという課題の存在を示唆している。また、その摂取方法も静脈内投与が必要である場合があるなど、必ずしも簡便とはいえない場合も多い。 These appetite-enhancing agents are said to cause an increase in the amount of food intake when administered, and are said to be effective in treating eating disorders and alleviating symptoms of anorexia even in healthy individuals. On the other hand, it has been reported that an increase in food intake by these conventional appetite enhancers leads to an increase in body weight (WO01 / 32182). This means that the use of conventional appetite enhancers requires proper use under the supervision of a doctor, and causes excessive weight gain due to increased food intake, resulting in the risk of obesity and lifestyle-related diseases resulting from it. This suggests the existence of the problem of having In addition, the method of ingestion often requires intravenous administration, and is not always convenient.
一方、食品であるトウガラシやトウガラシに含まれるカプサイシン類は、食欲を増進させる効果があることが報告されており（「消化管におけるＴＲＰＶ１の発現と機能」、日薬理誌（Folia Pharmacol. Jpn.)128,78〜81(2006)）、また、その代謝亢進作用により肥満を抑制することが報告されている（Journal of Nutrition 116(7)1272-8(1986)）。しかしながら、トウガラシやカプサイシン類は、その摂取にあたって、「辛味」や「刺激性」を有するという香味上の問題がある。同じくトウガラシに含まるカプサイシン類の類縁体で辛味が弱いとされるカプシエイト類であっても、その強度は低下するものの辛味や刺激性を引き起こすこと自体に変わりはなく、その刺激性から咳反射感受性試験の誘発物質になりうることが明らかにされている（「非喫煙健常者におけるカプサイシンとカプシエイトによる咳反射と口腔の辛味刺激感受性」山崎，都、東北大学博士学位論文、2009.3.25.）。 On the other hand, capsaicins contained in pepper and capsicum, which are foods, have been reported to have an effect of promoting appetite ("expression and function of TRPV1 in the gastrointestinal tract"), Journal of Japanese Pharmacology (Folia Pharmacol. Jpn.) 128, 78-81 (2006)), and it has been reported that obesity is suppressed by its metabolic enhancing action (Journal of Nutrition 116 (7) 1272-8 (1986)). However, capsicum and capsaicin have a flavor problem that they have “pungency” and “irritant” when ingested. Similarly, capsaicins, which are similar to capsaicins in capsicum, have a weak pungent taste, but their strength decreases, but they do not change the pungent taste and irritation itself, and the cough reflex susceptibility from their irritation It has been shown that it can be a test inducer ("Cough reflex by capsaicin and capsiate and sensitivity to the pungent taste of the oral cavity in healthy non-smokers" Yamazaki, Miyako, Tohoku University Doctoral Dissertation, 2009.3.25.)
上記のように、従来より、各種の食欲増進剤が報告され、開示されているが、現在までに報告されている食欲増進剤では、摂食量の増加に伴い体重増加を引き起こすという問題があったり、更には、香味上の制約から、容易かつ香味にも優れた状態で摂取することがしにくいという問題があった。したがって、食欲増進剤の提供において、容易かつ簡便に香味上優れた状態で摂取でき、安全かつ効果的に食欲を増進しつつ、体重の過剰な増加をもたらさない食欲増進剤を提供することからは、なお課題を残しているのが現状である。 As described above, various appetite enhancers have been reported and disclosed so far. However, the appetite enhancers reported to date have had the problem of causing weight gain as the amount of food intake increases. Furthermore, there is a problem that it is difficult to take in an easy and excellent state due to the restriction on flavor. Therefore, in providing an appetite enhancer, from providing an appetite enhancer that can be easily and easily consumed in an excellent flavor, safely and effectively increases appetite, and does not cause excessive weight gain. However, there are still problems to be solved.
本発明の課題は、容易かつ簡便に香味上優れた状態で摂取でき、安全かつ効果的に食欲を増進しつつ、体重の過剰な増加をもたらさない食欲増進剤を提供することにある。また、本発明の課題は、食欲増進剤による食欲増進作用に対して、体重増加を抑制する、体重増加抑制剤を提供することにある。 An object of the present invention is to provide an appetite enhancer that can be easily and simply ingested in an excellent flavor state and that can safely and effectively increase appetite while not causing excessive increase in body weight. Moreover, the subject of this invention is providing the weight gain inhibitor which suppresses a weight gain with respect to the appetite increase action by an appetite enhancer.
本発明者らは、上記課題を解決すべく、天然素材であり、安全かつ効果的に食欲を増進し、しかも、香味上優れた状態で摂取できる食欲増進物質について鋭意探索するなかで、ホップや、ユーカリノキに含まれ、好ましいヒノキ様の香味を有する芳香成分であるβ−ユーデスモールが、食欲増進作用を有することを見出し、そして、該有効成分を経口摂取させるという簡便な手段によって食欲増進効果をもたらしつつも、長期間の摂取によっても体重の過剰な増加を生じさせないことを発見し、これらの知見に基づいて本発明を完成するに至った。本発明の食欲増進物質を用いた場合の体重増加抑制は、その一つの原因として、体脂肪の増加抑制によって、その体重増加の抑制を発揮することができる。 In order to solve the above-mentioned problems, the inventors of the present invention have eagerly searched for an appetite-enhancing substance that is a natural material, promotes appetite safely and effectively, and can be ingested in a superior state of flavor. , Which is contained in Eucalyptus, is a fragrance component having a preferable cypress-like flavor, β-eudesmol has been found to have an appetite enhancing action, and an effect of promoting appetite by a simple means of orally ingesting the active ingredient It has been found that an excessive increase in body weight is not caused even by long-term intake, and the present invention has been completed based on these findings. As a cause of the suppression of weight gain when the appetite promoting substance of the present invention is used, the suppression of weight gain can be exhibited by suppressing the increase in body fat.
すなわち、本発明は、β−ユーデスモールを有効成分として含有する食欲増進及び／又は体重増加抑制剤からなる。本発明の食欲増進及び／又は体重増加抑制剤において、β−ユーデスモールからなる有効成分の含有量は、０．１４〜１００ｐｐｂであることが好ましい。本発明において、有効成分であるβ−ユーデスモールは、食欲増進作用を有し、体脂肪増加抑制等を原因とする体重増加抑制作用を有する。本発明の食欲増進剤は、体重増加を抑制することが可能な、食欲増進剤として提供することができる。また、食欲増進作用に対する体重増加抑制作用を有することから、食欲増進に対する体重増加抑制剤として提供することもできる。本発明の食欲増進及び／又は体重増加抑制剤は、経口摂取の形態で摂取することができるが、該食欲増進及び／又は体重増加抑制剤を、飲料や食品に添加して摂取することもできる。 That is, this invention consists of an appetite increase and / or body weight gain inhibitor which contains (beta) -eudesmol as an active ingredient. In the appetite enhancement and / or weight gain inhibitor of the present invention, the content of the active ingredient comprising β-eudesmol is preferably 0.14 to 100 ppb. In the present invention, β-eudesmol, which is an active ingredient, has an appetite enhancing action, and has an action to suppress weight gain due to suppression of body fat increase and the like. The appetite enhancer of the present invention can be provided as an appetite enhancer capable of suppressing weight gain. Moreover, since it has a body weight gain inhibitory action for an appetite promoting action, it can also be provided as a weight gain inhibitor for appetite boosting. The appetite enhancement and / or weight gain inhibitor of the present invention can be taken in the form of oral intake, but the appetite enhancement and / or weight gain inhibitor can also be added to beverages and foods. .
すなわち具体的には本発明は、［１］β−ユーデスモールを有効成分として含有する食欲増進剤や、［２］食欲増進剤が、体脂肪増加抑制効果を伴うものであることを特徴とする前記［１］に記載の食欲増進剤や、［３］β−ユーデスモールからなる有効成分の含有量が、０．１４〜１００ｐｐｂであることを特徴とする前記［１］又は［２］に記載の食欲増進剤や、［４］食欲増進剤が、β−ユーデスモールを有効成分として含有し、該有効成分の飲料中の含有量が０．１４〜１００ｐｐｂであり、かつ、アルコール含有量が１％未満である食欲増進用非アルコールドリンク飲料であることを特徴とする前記［３］に記載の食欲増進剤や、［５］β−ユーデスモールを有効成分として含有する食欲増進用組成物や、［６］食欲増進用組成物が、体脂肪増加抑制効果を伴うものであることを特徴とする前記［５］に記載の食欲増進用組成物や、［７］β−ユーデスモールからなる有効成分の含有量が、０．１４〜１００ｐｐｂであることを特徴とする前記［５］又は［６］に記載の食欲増進用組成物や、［８］食欲増進用組成物が、β−ユーデスモールを有効成分として含有し、該有効成分の飲料中の含有量が０．１４〜１００ｐｐｂであり、かつ、アルコール含有量が１％未満である食欲増進用非アルコールドリンク飲料であることを特徴とする前記［７］に記載の食欲増進用組成物からなる。
Specifically, the present invention is characterized in that [1] an appetite enhancer containing β-eudesmol as an active ingredient and [2] an appetite enhancer has an effect of suppressing body fat increase. The above-mentioned [1] or [2], wherein the content of the appetite enhancer according to [1] and the active ingredient comprising [3] β-eudesmol is 0.14 to 100 ppb and appetizer described in [4] appetite agent, beta-the user Death mall containing as an active ingredient, a content in the beverage of the active ingredient 0.14～100Ppb, and containing alcohol A non-alcoholic drink for promoting appetite, the amount of which is less than 1%, and an appetite enhancer as described in [3] above and [5] β-eudesmol for enhancing appetite Compositions and [6] appetite enhancing compositions The composition for appetite enhancement as described in [5] above, which has a body fat increase inhibitory effect, and the content of an active ingredient consisting of [7] β-eudesmol is 0.14 to The composition for promoting appetite according to the above [5] or [6], which is 100 ppb, or the composition for promoting appetite according to [8], containing β-eudesmol as an active ingredient, Appetite enhancement as described in [7] above, wherein the content of the component in the beverage is 0.14 to 100 ppb and the alcohol content is less than 1%, and is a non-alcoholic drink for promoting appetite A composition .
本発明は、容易かつ簡便に香味上優れた状態で摂取でき、安全かつ効果的に食欲を増進しつつ、体重の過剰な増加をもたらさない食欲増進剤を提供する。また、本発明は、食欲増進剤による食欲増進作用に対して、体重増加を抑制することから、該食欲増進作用に対する体重増加抑制剤を提供する。更に、本発明の食欲増進剤は、食欲増進作用に対して、体脂肪増加を抑制することから、該食欲増進作用に対する体脂肪増加抑制剤を提供する。 The present invention provides an appetite enhancer that can be ingested easily and simply in an excellent state of flavor and that promotes appetite safely and effectively, while not causing an excessive increase in body weight. Moreover, since this invention suppresses a body weight increase with respect to the appetite increase effect | action by an appetite enhancer, the weight increase inhibitor with respect to this appetite increase effect | action is provided. Furthermore, since the appetite enhancer of the present invention suppresses the increase in body fat with respect to the appetite promoting action, the body fat increase inhibitor against the appetite enhancing action is provided.
本発明は、β−ユーデスモールを有効成分として含有する食欲増進及び／又は体重増加抑制剤からなる。本発明においては、食欲増進剤による食欲増進作用に対して、体重増加を抑制することが可能であることから、食欲増進に対して体重増加を抑制することができる食欲増進剤を提供することができる。本発明のβ−ユーデスモールを有効成分として含有する食欲増進及び／又は体重増加抑制剤は、その体重抑制の原因の一つとして、食欲増進作用に対して、体脂肪増加を抑制する作用を有することから、食欲増進作用に対する体脂肪増加抑制剤として提供することができる。本発明における体脂肪増加抑制効果は、皮下脂肪増加抑制作用や内臓脂肪増加抑制作用によって発揮されるが、好ましくは内臓脂肪増加抑制作用により発揮される。 The present invention comprises an appetite enhancement and / or weight gain inhibitor containing β-eudesmol as an active ingredient. In the present invention, since it is possible to suppress the increase in body weight with respect to the appetite promoting action by the appetite enhancer, it is possible to provide an appetite enhancer capable of suppressing the increase in body weight against the increase in appetite. it can. The appetite enhancing and / or weight gain inhibitor containing β-eudesmol of the present invention as an active ingredient has an effect of suppressing body fat increase with respect to the appetite increasing action as one of the causes of the weight suppression. Since it has, it can provide as a body fat increase inhibitor with respect to an appetite increase action. The body fat increase inhibitory effect in the present invention is exhibited by the subcutaneous fat increase inhibitory action and the visceral fat increase inhibitory action, but is preferably exhibited by the visceral fat increase inhibitory action.
本発明においては、食欲増進及び／又は体重増加抑制剤の有効成分として、β−ユーデスモールを用いる。該有効成分である、β−ユーデスモールは、市販のものを用いてもよく、これらを含有する天然物や合成香料から精製したものを用いてもよい。また、これらを含有する天然物、合成香料、該天然物又は合成香料からの抽出物を、β−ユーデスモールの含有物として用いてもよい。 In the present invention, β-eudesmol is used as an active ingredient of an appetite promoting and / or weight gain inhibitor. As the active ingredient, β-eudesmol, commercially available products may be used, or those purified from natural products or synthetic fragrances containing these may be used. Moreover, you may use the natural product containing these, a synthetic | combination fragrance | flavor, the extract from this natural product or a synthetic | combination fragrance | flavor as a content of (beta) -eudesmol.
抽出に用いられる天然物としては、例えば、桑科（Moraceae）多年生植物に属する植物であるホップ（Humulus luplus）、フトモモ科（Myrtaceae）の常緑高木であるユーカリノキ（Eucalyptus globulus）等が挙げられる。これらの植物は、その植物体をそのまま用いてもよく、該植物体を物理化学的処理又は生物学的処理をして得られる処理物として用いてもよい。これらの植物の植物体として、ホップについては、葉、又は毬花があげられるが、毬花が好ましく用いられる。毬花のルプリン部分を用いてもよい。ホップとしてはドイツ・ヘルスブルッカー種、ドイツ・スパルトセレクト種、チエコ・ザーツ種があげられるが、β−ユーデスモールを高含有することから、ドイツ・ヘルスブルッカー種が好ましく用いられる。ユーカリノキ（ユーカリ）については、葉、小枝、花または果実があげられるが、葉が好ましく用いられる。 Examples of natural products used for extraction include hop (Humulus luplus), a plant belonging to the perennial plant of Moraceae, Eucalyptus globulus, which is an evergreen tree of Myrtaceae. These plants may be used as they are, or may be used as treated products obtained by physicochemical treatment or biological treatment of the plants. Examples of plant bodies of these plants include leaves and spikelets for hops, and spikelets are preferably used. You may use the lupulin part of the flower. Examples of hops include German health brooker species, German sparto select species, and Chieco-Saerts species, and since they contain a high content of β-eudesmol, German health brooker species are preferably used. Eucalyptus tree (eucalyptus) includes leaves, twigs, flowers or fruits, but leaves are preferably used.
植物体の物理化学的処理としては、天日乾燥、通風乾燥、凍結乾燥等による乾燥処理、ブレンダー、ホモジナイザー、ボールミル等による粉砕処理などがあげられ、物理化学的処理物としては、乾燥処理物、粉砕処理物等が挙げられる。生物学的処理としては、細菌、酵母等による発酵処理などがあげられ、生物学的処理物としては発酵処理物等が挙げられる。植物体の処理物の例としては、例えば、ホップ毬花の圧縮物であるホップペレットが挙げられる。本発明の植物体の抽出物としては、該植物体から、溶媒抽出、超臨界流体抽出、水蒸気蒸留等、植物体から物質を抽出する方法によって取得できる抽出物が挙げられるが、溶媒抽出が好ましい。 Examples of the physicochemical treatment of the plant include drying treatment by sun drying, ventilation drying, freeze drying, etc., pulverization treatment by a blender, a homogenizer, a ball mill and the like. A pulverized processed material etc. are mentioned. Examples of biological treatment include fermentation treatment with bacteria, yeast and the like, and examples of biological treatment products include fermentation treatment products. As an example of the processed material of a plant body, the hop pellet which is a compression product of a hop camellia is mentioned, for example. Examples of the plant extract of the present invention include extracts that can be obtained from the plant by a method of extracting a substance from the plant, such as solvent extraction, supercritical fluid extraction, steam distillation, etc., but solvent extraction is preferred. .
溶媒抽出に用いる溶媒としては、本発明に用いられる植物体又はその処理物からβ−ユーデスモールを抽出できる溶媒であれば、例えば水、精製水、脱イオン水、蒸留水等の水性媒体、アルコール、酢酸アルキル、脂肪族ケトン、脂肪族エーテル、脂肪族炭化水素、脂環式炭化水素等の有機溶媒等いずれでもよいが、水性媒体またはアルコールが好ましく、エタノールがより好ましく用いられる。溶媒は単独で用いてもよいし、複数を組み合わせた混合溶媒として用いてもよい。 As a solvent used for solvent extraction, an aqueous medium such as water, purified water, deionized water, distilled water, or the like can be used as long as it can extract β-eudesmol from the plant used in the present invention or a processed product thereof. Organic solvents such as alcohols, alkyl acetates, aliphatic ketones, aliphatic ethers, aliphatic hydrocarbons, and alicyclic hydrocarbons may be used, but aqueous media or alcohols are preferable, and ethanol is more preferably used. A solvent may be used independently and may be used as a mixed solvent which combined two or more.
溶媒抽出は、撹拌機、超音波発生器、還流抽出器、ソックスレー抽出器等、通常の溶媒抽出で使用される機器が用いられる。溶媒抽出に用いられる溶媒量は、特に制限はないが、例えば植物体１重量部に対して溶媒を０．１〜１００００重量部、好ましくは１〜１０００重量部、さらに好ましくは５〜１００重量部を用いて行う。抽出温度は、溶媒の融点以上、沸点以下の温度であれば、特に制限はないが、水性媒体では０〜１００℃が好ましく、２０〜８０℃がより好ましく、有機溶媒では０〜３００℃が好ましく、２０〜８０℃がより好ましい。 For the solvent extraction, equipment used in usual solvent extraction, such as a stirrer, an ultrasonic generator, a reflux extractor, a Soxhlet extractor, or the like is used. The amount of solvent used for solvent extraction is not particularly limited, but for example, 0.1 to 10,000 parts by weight, preferably 1 to 1000 parts by weight, and more preferably 5 to 100 parts by weight of solvent with respect to 1 part by weight of the plant. To do. The extraction temperature is not particularly limited as long as it is a temperature not lower than the melting point of the solvent and not higher than the boiling point, but is preferably 0 to 100 ° C in an aqueous medium, more preferably 20 to 80 ° C, and preferably 0 to 300 ° C in an organic solvent. 20-80 degreeC is more preferable.
抽出時間は、特に制限はないが、１分間〜１年間が好ましく、３０分間〜１週間がより好ましい。溶媒抽出が終了した後、得られた抽出液を、沈降分離、ケーク濾過、清澄濾過、遠心濾過、遠心沈降、圧搾、分離、フィルタープレス等の固液分離方法を用いて、好ましくは濾過により、抽出液を取得し、これを抽出物としてもよい。また、該固液分離方法によって得られた抽出残渣を、抽出溶媒でさらに抽出し、これを抽出物としてもよい。植物体から溶媒抽出、超臨界流体分離等の抽出方法により取得した抽出物は、更に、固液分離方法、濃縮または乾燥方法、精製方法等を用いて処理してもよい。 The extraction time is not particularly limited, but is preferably 1 minute to 1 year, more preferably 30 minutes to 1 week. After the solvent extraction is completed, the obtained extract is subjected to sedimentation separation, cake filtration, clarification filtration, centrifugal filtration, centrifugal sedimentation, compression, separation, filter press and the like, preferably by filtration, An extract may be obtained and used as an extract. Further, the extraction residue obtained by the solid-liquid separation method may be further extracted with an extraction solvent, and this may be used as an extract. The extract obtained from the plant body by extraction methods such as solvent extraction and supercritical fluid separation may be further processed using a solid-liquid separation method, a concentration or drying method, a purification method, and the like.
本発明の食欲増進及び体重増加抑制剤は、経口摂取により摂取される。該経口摂取の製剤形態としては、経口薬剤として用いられている各種の製剤形態を用いることができる。本発明の製剤組成物は、活性成分として、有効な量のβ−ユーデスモール（０．１４〜１００ｐｐｂ）を薬理的に許容される担体と均一に混合して製造できる。これらの製剤組成物は、経口投与に対して適する単位服用形態にあることが望ましい。経口摂取形態にある組成物の調製においては、何らかの有用な薬理的に許容される担体が使用できる。 The appetite promoting and weight gain inhibitor of the present invention is taken by oral ingestion. As the preparation forms for oral intake, various preparation forms used as oral drugs can be used. The pharmaceutical composition of the present invention can be produced by uniformly mixing an effective amount of β-eudesmol (0.14 to 100 ppb) as an active ingredient with a pharmacologically acceptable carrier. These pharmaceutical compositions are preferably in unit dosage forms suitable for oral administration. Any useful pharmacologically acceptable carrier can be used in preparing the compositions in oral form.
例えば懸濁剤およびシロップ剤のような経口液体調製物は、水、シュークロース、ソルビトール、フラクトース等の糖類、ポリエチレングリコール、プロピレングリコール等のグリコール類、ゴマ油、オリーブ油、大豆油等の油類、ｐ−ヒドロキシ安息香酸エステル類等の防腐剤、ストロベリーフレーバー、ペパーミント等のフレーバー類等を使用して製造できる。粉剤、丸剤、カプセル剤および錠剤は、ラクトース、グルコース、シュークロース、マンニトール等の賦形剤、でん粉、アルギン酸ソーダ等の崩壊剤、ステアリン酸マグネシウム、タルク等の滑沢剤、ポリビニルアルコール、ヒドロキシプロピルセルロース、ゼラチン等の結合剤、脂肪酸エステル等の表面活性剤、グリセリン等の可塑剤等を用いて製造できる。錠剤およびカプセル剤は、投与が容易であるという理由で、最も有用な単位経口投与剤である。錠剤やカプセル剤を製造する際には固体の製薬担体が用いられる。
また、注射剤は、蒸留水、塩溶液、グルコース溶液または塩水とグルコース溶液の混合物等から成る担体を用いて調製することができる。この際、常法に従い適当な助剤を用いて、溶液、懸濁液または分散液として調製される。
For example, oral liquid preparations such as suspensions and syrups include sugars such as water, sucrose, sorbitol and fructose, glycols such as polyethylene glycol and propylene glycol, oils such as sesame oil, olive oil and soybean oil, p -It can be produced using preservatives such as hydroxybenzoic acid esters, and flavors such as strawberry flavor and peppermint. Powders, pills, capsules and tablets are excipients such as lactose, glucose, sucrose, mannitol, starch, disintegrants such as sodium alginate, lubricants such as magnesium stearate and talc, polyvinyl alcohol, hydroxypropyl It can be produced using a binder such as cellulose and gelatin, a surfactant such as fatty acid ester, and a plasticizer such as glycerin. Tablets and capsules are the most useful unit oral dosages because they are easy to administer. When producing tablets and capsules, solid pharmaceutical carriers are used.
An injection can be prepared using a carrier comprising distilled water, a salt solution, a glucose solution, a mixture of salt water and a glucose solution, or the like. At this time, it is prepared as a solution, suspension or dispersion using an appropriate auxiliary agent according to a conventional method.
本発明の食欲増進及び体重増加抑制剤は、β−ユーデスモールを飲料に含有させ摂取することができる。該飲料は、β−ユーデスモール又はその含有物を、製造時、又は製造後に、飲料中のこれらの含有量が合計で０．１４〜１００ｐｐｂとなるように添加、含有させることにより製造することができるが、該飲料の製造は、β−ユーデスモール又はその含有物を、製造時、又は製造後に、該飲料中に添加、含有させる点を除き、非アルコール飲料（アルコール含有量が１％未満である飲料）の通常の製造に用いられる原料、添加物及び製造方法を用いるこができる。本発明の飲料中のβ−ユーデスモールの含有量は、市販のＧＣ／ＭＳ装置を用いるなど、常法により定量することができる。 The appetite promoting and weight gain inhibitor of the present invention can be ingested by containing β-eudesmol in a beverage. The beverage is produced by adding and containing β-eudesmol or a content thereof at the time of production or after production so that the content of the beverage is 0.14 to 100 ppb in total. However, the production of the beverage is a non-alcoholic beverage (with an alcohol content of 1%), except that β-eudesmol or its content is added to or contained in the beverage during or after production. Raw materials, additives, and production methods used in the normal production of beverages). The content of β-eudesmol in the beverage of the present invention can be quantified by a conventional method such as using a commercially available GC / MS apparatus.
本発明の食欲増進及び体重増加抑制剤は、非アルコール飲料等に適用することができる。かかる場合の非アルコール飲料としては、例えば、ミネラルウォーター、ニア・ウォーター、スポーツドリンク、茶飲料、乳飲料、コーヒー飲料、果汁入り飲料、野菜汁入り飲料、果汁および野菜汁飲料、炭酸飲料などが挙げられるが、これらに限定はされない。ノンアルコールビール等、アルコール含有量が１％未満のビール飲料であってもよい。ミネラルウォーターは、発泡性及び非発泡性のミネラルウォーターのいずれもが包含される。 The appetite enhancement and weight gain inhibitor of the present invention can be applied to non-alcoholic beverages and the like. Examples of such non-alcoholic beverages include mineral water, near water, sports drinks, tea drinks, milk drinks, coffee drinks, fruit juice drinks, vegetable juice drinks, fruit juices and vegetable juice drinks, and carbonated drinks. However, it is not limited to these. It may be a beer beverage having an alcohol content of less than 1%, such as non-alcohol beer. Mineral water includes both foaming and non-foaming mineral water.
上記非アルコール飲料における茶飲料とは、ツバキ科の常緑樹である茶樹の葉（茶葉）、又は茶樹以外の植物の葉若しくは穀類等を煎じて飲むための飲料をいい、発酵茶、半発酵茶、及び不発酵茶のいずれもが包含される。茶飲料の具体例としては、日本茶（例えば、緑茶、麦茶）、紅茶、ハーブ茶（例えば、ジャスミン茶）、中国茶（例えば、中国緑茶、烏龍茶）、ほうじ茶等が挙げられる。乳飲料とは、生乳、牛乳等またはこれらを原料として製造した食品を主原料とした飲料をいい、牛乳等そのもの材料とするものの他に、例えば、栄養素強化乳、フレーバー添加乳、加糖分解乳等の加工乳を原料とするものも包含される。 The tea drink in the non-alcoholic drinks refers to drinks for decocting tea leaves (tea leaves) that are evergreen trees of the camellia family, or leaves or cereals of plants other than tea trees, such as fermented tea, semi-fermented tea, And non-fermented tea are both included. Specific examples of tea beverages include Japanese tea (for example, green tea, barley tea), black tea, herbal tea (for example, jasmine tea), Chinese tea (for example, Chinese green tea, oolong tea), hoji tea, and the like. Milk beverages refer to beverages made mainly from raw milk, milk, etc. or foods made from these raw materials. In addition to those made of milk and other ingredients, for example, nutrient-enriched milk, flavored milk, and sugar-decomposed milk Those made from processed milk are also included.
果汁入り飲料や果汁および野菜汁入り飲料に用いられる果物としては、例えば、リンゴ、ミカン、ブドウ、バナナ、ナシ、モモ、マンゴーなどが挙げられる。また、野菜汁入り飲料や果汁および野菜汁入り飲料に用いられる野菜としては、例えば、トマト、ニンジン、セロリ、カボチャ、セロリ、キュウリなどが挙げられる。 Examples of fruits used in fruit juice-containing beverages and fruit and vegetable juice-containing beverages include apples, mandarin oranges, grapes, bananas, pears, peaches, mangoes, and the like. Examples of vegetables used in vegetable juice-containing beverages, fruit juices, and vegetable juice-containing beverages include tomato, carrot, celery, pumpkin, celery, and cucumber.
本発明の食欲増進及び体重増加抑制剤を飲料等に適用するにあたり、β−ユーデスモール以外の食欲増進効果または体重増加抑制効果を有する素材を配合することができる。食欲増進効果または体重増加抑制効果を有する素材としては、例えば、ホップ抽出物、イソフムロン類、ヘスペリジン、カテキン、ケルセチン、コーヒー豆マンノオリゴ糖、ジアシルグリセロール、中鎖脂肪酸、ドコサヘキサエン酸、エイコサペンタエン酸、グロビン蛋白分解物、ベータコングリニシン、クロロゲン酸類、１３−オキソ−９，１１−オクタデカジエン酸、難消化デキストリン、レスベラトロール類、紅茶重合ポリフェノール類、烏龍茶重合ポリフェノール、ワイン抽出物、コーヒー豆抽出物、トマト抽出物などが挙げられるが、これらに限定はされない。 In applying the appetite enhancement and weight gain inhibitor of the present invention to beverages and the like, materials having an appetite enhancement effect or weight gain inhibition effect other than β-eudesmol can be blended. Examples of materials having an appetite enhancing effect or a weight gain suppressing effect include hop extract, isohumulones, hesperidin, catechin, quercetin, coffee bean manno-oligosaccharide, diacylglycerol, medium chain fatty acid, docosahexaenoic acid, eicosapentaenoic acid, globin protein Degradation product, beta-conglinicin, chlorogenic acids, 13-oxo-9,11-octadecadienoic acid, indigestible dextrin, resveratrol, black tea polymerized polyphenols, oolong tea polymerized polyphenol, wine extract, coffee bean extract , Tomato extract and the like, but are not limited thereto.
本発明は、食欲増進作用及び体重増加抑制作用を有する食欲増進剤及び体重増加抑制剤を提供する。本発明の有効成分であるユーデスモールを食欲増進剤として摂取する際には、ヒト、マウス、ラット、ウサギ、イヌ、ネコ等の動物等に対して経口または非経口的に安全に投与することができ、投与対象の年齢、性別、体重、又は投与方法などに応じて適宜決定することができる。例えば成人一人が、β−ユーデスモールを一日当たり１０００μｇ〜０．０２５μｇ、好ましくは５００μｇ〜０．０２５μｇ、より好ましくは５μｇ〜０．０２５μｇとなるように摂取することが好ましい。 The present invention provides an appetite enhancer and a weight gain inhibitor having an appetite enhancing action and a weight gain inhibiting action. When ingesting udesmol, the active ingredient of the present invention, as an appetite enhancer, it should be safely administered orally or parenterally to animals such as humans, mice, rats, rabbits, dogs, cats, etc. It can be appropriately determined according to the age, sex, body weight, or administration method of the administration subject. For example, it is preferable that one adult takes β-eudesmol at 1000 μg to 0.025 μg, preferably 500 μg to 0.025 μg, more preferably 5 μg to 0.025 μg per day.
β−ユーデスモールを一日当たり摂取する量を一回であるいは数回に分けて摂取することもでき、例えば一日当たり摂取する量を一回で摂取する場合には、１回当たりの単位包装形態の食品はβ−ユーデスモール１０００μｇ〜０．０２５μｇ含有する。 The amount of β-eudesmol taken per day can be taken once or divided into several times. For example, when the amount taken per day is taken once, the unit packaging form per time This food contains 1000 μg to 0.025 μg of β-eudesmol.
「１回当たりの単位包装形態」からなる食品とは、１回あたりに摂取する量が予め定められた形態の食品である。本明細書にて食品とは、経口摂取し得るもの（医薬品を除く）を広く包含する概念であり、所謂「食べ物」のみならず飲料、健康補助食品、保健機能食品、サプリメント等を含む。１回当たりの単位包装形態としては、例えば、飲料、キャンディー、チューイングガム、ゼリー、プリン、ヨーグルト等の場合にはパック、包装、ボトル等で一定量を規定する形態が挙げられ、顆粒・粉末・スラリー状の食品の場合には、包装などで一定量を規定できる、あるいは容器などに１回当たりの摂取量を表示してある形態が挙げられる。 The food consisting of “unit packaging form per time” is a food in a form in which the amount to be taken per time is predetermined. The term “food” as used herein is a concept that broadly encompasses those that can be taken orally (excluding pharmaceuticals) and includes not only “food” but also beverages, health supplements, health functional foods, supplements, and the like. Examples of the unit packaging form per time include, for example, in the case of beverages, candy, chewing gum, jelly, pudding, yogurt, etc., a form in which a certain amount is defined by a pack, packaging, bottle, etc., granule / powder / slurry In the case of food in the form of a food, a certain amount can be specified by packaging or the like, or the amount of intake per time is displayed on a container or the like.
本発明は、β−ユーデスモールを用いる食欲を増進する方法及び／又は体重増加を抑制する方法を提供する。また本発明は、β−ユーデスモールを摂取させることを特徴とする、食欲を増進する方法及び／又は体重増加を抑制する方法を提供する。特に、本発明の食欲を増進する方法及び／又は体重増加を抑制する方法は、その体重増加の抑制において、体脂肪の増加抑制作用等を有することから、食欲の増進における体脂肪の増加抑制方法を提供することができる。なお、本発明の食欲を増進する方法及び／又は体重増加を抑制する方法は、ヒトに対する医療行為として行われる食欲増進及び／又は体重増加抑制の方法は対象としていない。 The present invention provides a method for promoting appetite and / or a method for suppressing weight gain using β-eudesmol. The present invention also provides a method for increasing appetite and / or a method for suppressing weight gain, characterized by ingesting β-eudesmol. In particular, the method for increasing appetite and / or the method for suppressing weight gain according to the present invention has a body fat increase inhibitory action and the like in suppressing the body weight gain. Can be provided. In addition, the method for increasing appetite and / or the method for suppressing weight gain according to the present invention does not cover the method for increasing appetite and / or suppressing weight gain performed as a medical practice for humans.
本発明は、β−ユーデスモールを含有する飲食品を摂取させることを特徴とする、食欲を増進する方法及び／又は体重増加を抑制する方法を提供する。飲食品は、有効な量のβ−ユーデスモール（０．１４〜１００ｐｐｂ）を含有させることができる。特に、本発明のβ−ユーデスモールを含有する飲食品を摂取させることを特徴とする、食欲を増進する方法及び／又は体重増加を抑制する方法は、その体重増加の抑制において、体脂肪の増加抑制作用等を有することから、食欲の増進における体脂肪の増加抑制方法を提供することができる。 The present invention provides a method for enhancing appetite and / or a method for suppressing weight gain, characterized by ingesting a food or drink containing β-eudesmol. The food and drink can contain an effective amount of β-eudesmol (0.14 to 100 ppb). In particular, the method for enhancing appetite and / or the method for suppressing weight gain, characterized by ingesting a food or drink containing β-eudesmol of the present invention, Since it has an increase suppressing action and the like, it is possible to provide a method for suppressing increase in body fat in promoting appetite.
以下、実施例を挙げて本発明を更に具体的に説明するが、本発明はこれらの実施例に限定されるものではない。 EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated further more concretely, this invention is not limited to these Examples.
［１．β−ユーデスモール飲水混合投与時の味覚的忌避性検証（ラット）］ [1. Examination of taste repellency at the time of beta-eudesmol drinking administration (rat)]
「試験１」
１２時間毎の明暗周期（８時〜２０時まで点灯）下に２４℃の恒温動物室にて１週間以上順化飼育した体重約３００ｇのWistar系雄ラット（９週齢）を試験に用いた。試験前の体重をもとに３群に分け（ｎ＝５）、個別飼育を行った。試験実施前１６時間絶水させ、その後に一匹に対して２本の給水ボトルを与え、それぞれの重量を給水開始１５分後に測定し、飲水量を算出した。一匹のラットに与える２本の給水ボトルは以下の組み合わせとした。
０．５％カルボキシメチルセルロース（ＣＭＣ）：２本。
０．５％ＣＭＣ：１本及び５ｐｐｂβ−ユーデスモール（０．５％ＣＭＣ）１本。
０．５％ＣＭＣ：１本及び５０ｐｐｂβ−ユーデスモール（０．５％ＣＭＣ）１本。
"Test 1"
Wistar male rats (9 weeks old) having a body weight of about 300 g and housed in a constant temperature animal room at 24 ° C. under a light / dark cycle every 12 hours (lighted from 8 o'clock to 20 o'clock) for one week or more were used for the test. . Based on the body weight before the test, it was divided into 3 groups (n = 5) and reared individually. Water was drained for 16 hours before the test, and then two water bottles were given to one animal. The weight of each bottle was measured 15 minutes after the start of water supply, and the amount of water consumed was calculated. Two water bottles given to one rat were combined as follows.
0.5% carboxymethylcellulose (CMC): 2 bottles.
0.5% CMC: 1 and 5 ppbβ-eudesmol (0.5% CMC).
0.5% CMC: 1 and 50ppbβ-eudesmol (0.5% CMC).
一日以上の間隔をあけた後に群を入れ替え３回試験を繰り返すクロスオーバー試験を実施した。結果は、２本の給水ボトルの飲水量の合計を１００％としたときのβ−ユーデスモールを含むボトルの飲水量を百分率で示した。コントロールとしてはβ−ユーデスモールを全く含まない０．５％ＣＭＣのみのデータを示した。有意差検定は２本の給水ボトル間の飲水量で実施した。 After an interval of one day or more, the group was switched and a crossover test was repeated 3 times. As a result, the amount of drinking water of the bottle containing β-eudesmol when the total amount of drinking water of the two water supply bottles was taken as 100% was expressed as a percentage. As a control, only 0.5% CMC data containing no β-eudesmol was shown. The significant difference test was carried out based on the amount of water consumed between two water bottles.
（結果）
味覚的な忌避性がない場合にはグラフ中の値は５０％となるが、５ｐｐｂ、５０ｐｐｂともにほぼ５０％となり、対照となる０．５％ＣＭＣの飲水量との間に有意差は認められなかった（図１：二瓶選択試験によるβ−ユーデスモールの味覚的忌避性の検証結果）。有意差検定はStudent t-testにより行った。
(result)
When there is no taste repellency, the value in the graph is 50%, but both 5 ppb and 50 ppb are almost 50%, and there is a significant difference between the water consumption of 0.5% CMC as a control. (FIG. 1: Verification result of taste repellency of β-eudesmol by two-bottle selection test). Significant difference test was performed by Student t-test.
「試験２」
１２時間毎の明暗周期（８時〜２０時まで点灯）下に２４℃の恒温動物室にて１週間以上順化飼育した体重約３００ｇのWistar系雄ラット（９週齢）を試験に用いた。試験前３日間の体重等をもとにβ−ユーデスモール投与群（ｎ＝２０）とコントロール群（ｎ＝２０）に群分けを行った。ラットは個別飼育を行った。一方、β−ユーデスモールを、０．１４ｐｐｂ含む０．５％カルボキシメチルセルロース（ＣＭＣ）水溶液（以下、β−ユーデスモール０．１４ｐｐｂＣＭＣ水溶液という）を調製した。また、β−ユーデスモールを含まないＣＭＣ水溶液をコントロールとして作製した。
"Test 2"
Wistar male rats (9 weeks old) having a body weight of about 300 g and housed in a constant temperature animal room at 24 ° C. under a light / dark cycle every 12 hours (lighted from 8 o'clock to 20 o'clock) for one week or more were used for the test. . Based on the body weight and the like for 3 days before the test, the group was divided into a β-eudesmol administration group (n = 20) and a control group (n = 20). Rats were individually housed. Meanwhile, a 0.5% carboxymethylcellulose (CMC) aqueous solution (hereinafter referred to as β-eudesmol 0.14 ppb CMC aqueous solution) containing β-eudesmol 0.14 ppb was prepared. Moreover, the CMC aqueous solution which does not contain (beta) -eudesmol was produced as control.
（結果）
β−ユーデスモール群には、β−ユーデスモール０．１４ｐｐｂＣＭＣ水溶液を、コントロール群にはＣＭＣ水溶液を、それぞれ飲水ボトルを用いて２８日間連続で自由に摂取させた。その結果、試験開始２、１６、１８日目でβ−ユーデスモール群の方がコントロール群に対して体重あたりの飲水量が有意に増加する等、試験期間を通じてβ−ユーデスモール群でやや多い傾向であったが、試験期間全体を通じては有意差が認められなかった（ｐ＝０．１８）（図２：自由飲水によるβ−ユーデスモールの味覚的忌避性の検証結果）。試験期間を通じた総飲水量はβ−ユーデスモール群では９６６．８ｍｌ、コントロール群では９３９．８ｍｌであった。体重あたりの飲水量の有意差検定は、群間の各日の比較はStudent t-testにて、試験期間全体を通じてはANOVA with repeated measuresにて行った。
(result)
The β-eudesmol group was freely ingested with β-eudesmol 0.14 ppb CMC aqueous solution, and the control group was freely ingested with CMC aqueous solution for 28 consecutive days using drinking water bottles. As a result, the β-eudesmol group slightly increased in the β-eudesmol group throughout the test period, such as the β-eudesmol group significantly increased the amount of water per body weight compared to the control group on the second, 16th, and 18th days after the start of the test. Although there was a large tendency, no significant difference was observed throughout the test period (p = 0.18) (FIG. 2: verification result of taste repellency of β-eudesmol by free drinking). Total drinking water throughout the test period was 966.8 ml in the β-eudesmol group and 939.8 ml in the control group. The test of significant difference in the amount of water consumed per body weight was performed by Student t-test for comparison between groups, and ANOVA with repeated measures throughout the test period.
「試験１」及び「試験２」の結果から、β−ユーデスモールに味覚的な忌避性がないことが確認された。 From the results of “Test 1” and “Test 2”, it was confirmed that β-eudesmol had no taste repellency.
［２．β−ユーデスモール飲水混合投与時の摂食量と体重変化率（ラット）］ [2. Food intake and body weight change rate after administration of β-eudesmol drinking water (rat)]
「試験１」
１２時間毎の明暗周期（８時〜２０時まで点灯）下に２４℃の恒温動物室にて１週間以上順化飼育した体重約３００ｇのWistar系雄ラット（約９週齢）を試験に用いた。３日間の摂食量と体重をもとにβ−ユーデスモール投与群（ｎ＝２０）とコントロール群（ｎ＝２０）に群分けを行った。
"Test 1"
A Wistar male rat (approx. 9 weeks old) weighing approximately 300 g and housed in a constant temperature animal room at 24 ° C under a light / dark cycle every 12 hours (lighted from 8 to 20 o'clock) for one week or more is used for the test. It was. Based on the amount of food intake and body weight for 3 days, the group was divided into a β-eudesmol administration group (n = 20) and a control group (n = 20).
一方、β−ユーデスモールを、０．１４ｐｐｂ含む０．５％カルボキシメチルセルロース（ＣＭＣ）水溶液（以下、β−ユーデスモール０．１４ｐｐｂＣＭＣ水溶液という）を調製した。また、β−ユーデスモールを含まないＣＭＣ水溶液をコントロールとして作製した。β−ユーデスモール群にはβ−ユーデスモール０．１４ｐｐｂＣＭＣ水溶液を、コントロール群にはＣＭＣ水溶液を、それぞれ飲水ボトルを用いて２８日間連続で自由に摂取させた。その間、粉末給餌器を用いて給餌し、自由に摂食させた。その間の体重の変化率について試験開始前日の値を１００％として示す。一日あたりの摂食量は体重で補正した値を示す。 Meanwhile, a 0.5% carboxymethylcellulose (CMC) aqueous solution (hereinafter referred to as β-eudesmol 0.14 ppb CMC aqueous solution) containing β-eudesmol 0.14 ppb was prepared. Moreover, the CMC aqueous solution which does not contain (beta) -eudesmol was produced as control. A β-eudesmol 0.14 ppb CMC aqueous solution was freely given to the β-eudesmol group, and a CMC aqueous solution was freely taken for 28 consecutive days using a drinking bottle for the control group. Meanwhile, they were fed using a powder feeder and fed freely. The value on the day before the start of the test is shown as 100% for the rate of change in body weight during that time. The amount of food intake per day is a value corrected by body weight.
（結果）
β−ユーデスモール群はコントロール群に対して測定した全ての日において体重あたりの摂食量の平均値が高く、試験開始９、１５、１６、１８、２１、２８日目では有意差も認められた。また、試験期間を通じた有意差検定の結果でも、有意差も認められた（ｐ＜０．０１）（図３）。最終的な総摂食量の平均値はβ−ユーデスモール群では６７４．４ｇ、コントロール群では６６８．０ｇであった。
(result)
In the β-eudesmol group, the average value of the amount of food intake per body weight was high on all the days measured with respect to the control group, and a significant difference was observed on the 9th, 15th, 16th, 18th, 21st and 28th days of the test. It was. In addition, a significant difference was also found in the result of the significant difference test throughout the test period (p <0.01) (FIG. 3). The average value of the final total food intake was 674.4 g in the β-eudesmol group and 668.0 g in the control group.
上記のように、β−ユーデスモール群では摂食量が有意に多いにもかかわらず、試験期間を通じた体重増加率にはコントロール群との間に有意差はなく（ｐ＝０．４７）、最終的なβ−ユーデスモール群の体重増加率の平均値（１３４．５％）はむしろコントロール群の平均値（１３４．８％）よりも低く抑えられ、解剖時に測定した臓器重量（精巣周囲脂肪、腎周囲脂肪、肝臓）にも有意差は認められなかった（図３：自由飲水によるβ−ユーデスモールの摂食増加作用と体重の過剰な増加抑制作用の試験結果）。体重あたりの摂食量、及び体重増加率の有意差検定は、群間の各日の比較はStudent t-testにて、試験期間全体を通じてはanalysis of variance（ＡＮＯＶＡ）with repeated measures with repeated measuresにて行った。解剖時の臓器重量の有意差検定はStudent t-testにて行った。 As noted above, despite the significantly higher food intake in the β-eudesmol group, there was no significant difference between the control group and the weight gain rate throughout the study period (p = 0.47) The average weight gain rate (134.5%) of the final β-eudesmol group was kept lower than the average value (134.8%) of the control group, and the organ weight measured at the time of dissection (peripheral testis) Fat, perirenal fat, and liver) were also not significantly different (FIG. 3: test results of β-eudesmol's feeding-increasing effect and excessive body weight-inhibiting effect of free drinking). The significant difference test of the amount of food intake per body weight and the rate of weight gain is based on Student t-test for comparison of each day between groups, and analysis of variance (ANOVA) with repeated measures with repeated measures throughout the test period. went. A significant difference test of organ weight at the time of dissection was performed by Student t-test.
「試験２」
β−ユーデスモールの有効濃度を検証するため、以下の試験を行った。β−ユーデスモールを、０．１４ｐｐｂ含む０．５％カルボキシメチルセルロース（ＣＭＣ）水溶液（以下、β−ユーデスモール０．１４ｐｐｂＣＭＣ水溶液という）及びβ−ユーデスモールを、１．４ｐｐｂ含む０．５％カルボキシメチルセルロース（ＣＭＣ）水溶液（以下、β−ユーデスモール１．４ｐｐｂＣＭＣ水溶液という）を調製した。また、β−ユーデスモールを含まないＣＭＣ水溶液をコントロールとして作製した。
"Test 2"
In order to verify the effective concentration of β-eudesmol, the following test was conducted. 0.5% carboxymethyl cellulose (CMC) aqueous solution containing 0.14 ppb of β-eudesmol (hereinafter referred to as β-eudesmol 0.14 ppb CMC aqueous solution) and β-eudesmol 0.5 g containing 1.4 ppb % Carboxymethylcellulose (CMC) aqueous solution (hereinafter, referred to as β-eudesmol 1.4 ppb CMC aqueous solution) was prepared. Moreover, the CMC aqueous solution which does not contain (beta) -eudesmol was produced as control.
試験１と同様の方法でラットを用いた試験を実施した。体重と摂食量をもとにβ−ユーデスモール０．１４ｐｐｂ投与群（ｎ＝１２）、β−ユーデスモール１．４ｐｐｂ投与群（ｎ＝１２）、及びコントロール群（ｎ＝１２）に群分けを行った。β−ユーデスモール０．１４ｐｐｂ群にはβ−ユーデスモール０．１４ｐｐｂＣＭＣ水溶液を、β−ユーデスモール１．４ｐｐｂ群にはβ−ユーデスモール１．４ｐｐｂＣＭＣ水溶液を、コントロール群にはＣＭＣ水溶液をそれぞれ飲水ボトルを用いて３３日間連続で自由に摂取させた。 A test using rats was carried out in the same manner as in Test 1. Based on body weight and food intake, β-eudesmol 0.14 ppb administration group (n = 12), β-eudesmol 1.4 ppb administration group (n = 12), and control group (n = 12) Divided. β-eudesmol 0.14 ppb group for β-eudesmol 0.14 ppb CMC aqueous solution, β-eudesmol 1.4 ppb group for β-eudesmol 1.4 ppb CMC aqueous solution, and control group for CMC aqueous solution Were ingested freely for 33 consecutive days using water bottles.
（結果）
結果、試験期間中の総摂食量の平均値はβ−ユーデスモール０．１４ｐｐｂ群では８５０．２ｇ、β−ユーデスモール１．４ｐｐｂ群では８４６．２２ｇとなり、コントロール群の８３８．４３ｇを上回った。このとき試験開始からの体重増加率はβ−ユーデスモール０．１４ｐｐｂ群では１３６．８％、β−ユーデスモール１．４ｐｐｂ群では１３８．９ｇとなり、コントロール群の１４０．７％を下回った。したがって、少なくともβ−ユーデスモールを０．１４ｐｐｂから１．４ｐｐｂの濃度で摂取する場合、体重の過剰な増加を抑制しつつ、摂食量を増加させる効果があると認められた。
(result)
As a result, the average value of the total food intake during the test period was 850.2 g in the β-eudesmol 0.14 ppb group and 846.42 g in the β-eudesmol 1.4 ppb group, exceeding the control group of 838.43 g. It was. At this time, the rate of weight gain from the start of the test was 136.8% in the β-eudesmol 0.14 ppb group and 138.9 g in the β-eudesmol 1.4 ppb group, which was lower than 140.7% of the control group. . Therefore, when at least β-eudesmol was ingested at a concentration of 0.14 ppb to 1.4 ppb, it was recognized that there was an effect of increasing food intake while suppressing an excessive increase in body weight.
［３．β−ユーデスモール投与時のグレリン濃度（ラット）］ [3. Ghrelin concentration at the time of β-eudesmol administration (rat)]
「試験１」
実施例２の試験１の２８日間β−ユーデスモール飲水混合投与試験期間終了後、ラットを一晩（約１８時間）絶食させ、ウレタン麻酔し、頚静脈から２ｍｌ採血を行った。採取した血液から血漿を分離し、オクタノイルグレリン（活性型グレリン）、及びデスアシルグレリン（不活性型グレリン）の濃度をＥＬＩＳＡにて測定した（図４）。その結果、β−ユーデスモール群はコントロール群に対してオクタノイルグレリン（活性型グレリン）、及びデスアシルグレリン（不活性型グレリン）ともに平均値が上昇し、オクタノイルグレリン（活性型グレリン）では統計的な有意差が認められたことから、β−ユーデスモールによる摂食量増加作用には、血中の活性型グレリンの増加が寄与している可能性が考えられた（図４：、β−ユーデスモールの２８日間自由飲水投与後の血中グレリン濃度を測定した結果）。
"Test 1"
After the 28-day β-eudesmol drinking water mixed administration test period in Test 1 of Example 2, the rats were fasted overnight (about 18 hours), urethane anesthetized, and 2 ml blood was collected from the jugular vein. Plasma was separated from the collected blood, and the concentrations of octanoyl ghrelin (active ghrelin) and desacyl ghrelin (inactive ghrelin) were measured by ELISA (FIG. 4). As a result, the average value of the β-eudesmol group increased in both octanoyl ghrelin (active ghrelin) and desacyl ghrelin (inactive ghrelin) compared to the control group, and octanoyl ghrelin (active ghrelin) Since a statistically significant difference was observed, it was considered that the increase in active ghrelin in the blood may contribute to the effect of β-eudesmol on increasing food intake (FIG. 4: β -Results of measuring blood ghrelin concentration after 28 days of free drinking administration of udesmol).
β−ユーデスモールの摂取により、血中の活性化グレリンが上昇することを確認するため、以下の試験を行った。１２時間毎の明暗周期（８時〜２０時まで点灯）下に２４℃の恒温動物室にて１週間以上順化飼育した体重約３００ｇのWistar系雄ラット（９週齢）を実験に用いた。体重を元に群分けを行った。ラットを一晩（約１８時間）絶食させた後、ウレタン麻酔し、３７度にセットしたホットプレート上で保温した状態で、経口で胃内にカニューレを挿入した。 In order to confirm that ingestion of β-eudesmol increased activated ghrelin in the blood, the following test was performed. Wistar male rats (9 weeks old) weighing approximately 300 g and housed in a constant temperature animal room at 24 ° C. under a light-dark cycle every 12 hours (lighted from 8 o'clock to 20 o'clock) for one week or more were used in the experiment. . Grouping was performed based on body weight. Rats were fasted overnight (about 18 hours), then urethane anesthetized, and warmed on a hot plate set at 37 degrees and orally cannulated into the stomach.
カニューレを用いてβ−ユーデスモール５ｐｐｂ含有ＣＭＣ水溶液またはβ−ユーデスモール５０ｐｐｂ含有ＣＭＣ水溶液を１．０ｍｌ／３００ｇ体重を胃内投与した。その際、投与５分前、及び投与後１５，３０，６０分後に３００μｌづつ頚静脈から採血を行った。また、β−ユーデスモールを含まないＣＭＣ水溶液をコントロールとして用いる以外は同様の操作を行い、これをコントロール投与群とした。採取した血液から血漿を分離し、オクタノイルグレリン（活性型グレリン）、及びデスアシルグレリン（不活性型グレリン）の濃度を市販のＥＬＩＳＡにて測定した。測定結果は投与前の測定値を１００％とし、経時的な変化として示す（図５：β−ユーデスモールの単回投与後の血中グレリン濃度を測定した結果）。 Using a cannula, 1.0 ml / 300 g body weight of a CMC aqueous solution containing β-eudesmol 5 ppb or a CMC aqueous solution containing β-eudesmol 50 ppb was intragastrically administered. At that time, blood was collected from the jugular vein every 5 μl before administration and 15, 30, 60 minutes after administration. Further, the same operation was performed except that a CMC aqueous solution containing no β-eudesmol was used as a control, and this was used as a control administration group. Plasma was separated from the collected blood, and the concentrations of octanoyl ghrelin (active ghrelin) and desacyl ghrelin (inactive ghrelin) were measured by a commercially available ELISA. The measurement results are shown as changes over time with the measured value before administration as 100% (FIG. 5: results of measuring blood ghrelin concentration after single administration of β-eudesmol).
図５に示すとおり、β−ユーデスモール５ｐｐｂ含有ＣＭＣ、またはβ−ユーデスモール５０ｐｐｂ含有ＣＭＣ水溶液の投与により、血漿中のオクタノイルグレリンの濃度はコントロール群よりも常に高い値を推移した。また、一方、デスアシルグレリンについては一定の傾向は認められなかった。 As shown in FIG. 5, the concentration of octanoyl ghrelin in plasma was constantly higher than that in the control group by administration of β-eudesmol 5 ppb-containing CMC or β-eudesmol 50 ppb-containing CMC aqueous solution. On the other hand, no constant tendency was observed for desacyl ghrelin.
［４．β-ユーデスモール投与時の肩甲間褐色脂肪組織交感神経もしくは副睾丸白色脂肪組織交感神経遠心枝活動変化（ラット）］ [4. Change in activity of cranial interscapular brown adipose tissue sympathetic nerve or paratestinal white adipose tissue sympathetic nerve centrifuge branch during beta-eudesmol administration (rat)
β-ユーデスモールが摂食量を増加させつつも体重増加を抑制する理由を検証するため、体熱産生を制御する肩甲間褐色脂肪組織交感神経活動、及び脂肪分解を制御する副睾丸白色脂肪組織交感神経に与える影響を検討した。このとき白色脂肪組織の交感神経の興奮は脂肪分解を促進し抗肥満効果をもたらすこと、及び褐色脂肪組織の交感神経興奮は熱産生上昇をもたらし抗肥満効果をもたらすことが知られているため（自律神経による生体制御とその利用、永井克也、化学と生物 Vol. 51, No. 3 2013）、両神経活動がβ-ユーデスモールにより活性化されれば、摂食量の増加によっても体脂肪である白色脂肪組織（クロロゲン酸類の体脂肪低減効果、http://www.kao.co.jp/rd/eiyo/about-cga/cga03.html）での脂肪分解を促進し、体脂肪増加抑制効果をもたらすと考えられる。 To examine why β-eudesmol suppresses weight gain while increasing food intake, interscapular brown adipose tissue sympathetic nerve activity that controls body heat production, and accessory testicular white fat that controls lipolysis The effect on tissue sympathetic nerve was examined. At this time, it is known that sympathetic excitement of white adipose tissue promotes lipolysis and brings anti-obesity effect, and sympathetic excitement of brown adipose tissue raises heat production and produces anti-obesity effect ( Biological control by the autonomic nerve and its use, Katsuya Nagai, Chemistry and Biology Vol. 51, No. 3 2013), if both nerve activities are activated by β-eudesmol, even if the amount of food intake increases, Promotes lipolysis and suppresses body fat increase in a white adipose tissue (chlorogenic acids reduce body fat, http://www.kao.co.jp/rd/eiyo/about-cga/cga03.html) It is thought to bring about.
１２時間毎の明暗周期（８時〜２０時まで点灯）下に２４℃の恒温動物室にて１週間以上飼育した体重約３００ｇのWistar系雄ラット（約９週齢）を３時間絶食させた。絶食後、ウレタン麻酔し、胃内投与用のカニューレを挿入し、肩甲間褐色脂肪組織交感神経もしくは副睾丸白色脂肪組織交感神経の遠心枝を銀電極で吊り上げ、それら神経の電気活動を測定した（Shen J, et al. Neurosci. Lett. 383.188-193, 2005；Tanida M, et al., Neurosci. Lett. 389: 109-114, 2005）。 A Wistar male rat (about 9 weeks old) with a body weight of about 300 g kept in a constant temperature animal room at 24 ° C. under a light-dark cycle every 12 hours (lighted from 8 to 20) was fasted for 3 hours. . After fasting, urethane anesthesia was performed, a cannula for intragastric administration was inserted, and the cranial brown adipose tissue sympathetic nerve or the epididymal white adipose tissue sympathetic nerve was lifted with a silver electrode, and the electrical activity of these nerves was measured. (Shen J, et al. Neurosci. Lett. 383.188-193, 2005; Tanida M, et al., Neurosci. Lett. 389: 109-114, 2005).
一方、β−ユーデスモールを５ｐｐｂ含む０．５％カルボキシメチルセルロース（ＣＭＣ）水溶液（以下、β−ユーデスモールＣＭＣ水溶液という）を調製した。これらの神経の電気活動測定値が落ち着いた時期にそれぞれのβ−ユーデスモールＣＭＣ水溶液を１．０ｍｌ／３００ｇ体重となるように胃内投与し、その際生じるこれらの肩甲間褐色脂肪組織交感神経もしくは副睾丸白色脂肪組織交感神経遠心枝の電気活動の変化を９０分間ずつ電気生理学的に測定した。なお、手術開始から測定終了までチューブを気管に挿入して気道を確保し、保温装置にて体温（ラット直腸温）を３５．０±０．５℃に保つようにした。また、β−ユーデスモールを含まないＣＭＣ水溶液をコントロールとして用いる以外は同様の操作を行い、これをコントロール投与群とした。 On the other hand, a 0.5% carboxymethylcellulose (CMC) aqueous solution (hereinafter referred to as β-eudesmol CMC aqueous solution) containing 5 ppb of β-eudesmol was prepared. When the measured electrical activity of these nerves settled, each β-eudesmol CMC aqueous solution was intragastrically administered to a body weight of 1.0 ml / 300 g, and these interscapular brown adipose tissue sympathies occurred. Changes in electrical activity of nerve or paratesticular white adipose tissue sympathetic nerve branch were electrophysiologically measured every 90 minutes. The tube was inserted into the trachea from the start of surgery to the end of measurement to secure the airway, and the body temperature (rat rectal temperature) was maintained at 35.0 ± 0.5 ° C. with a heat retaining device. Further, the same operation was performed except that a CMC aqueous solution containing no β-eudesmol was used as a control, and this was used as a control administration group.
これらの神経活動のデータは５分間毎の５秒あたりの発火頻度（pulse／５ｓ）の平均値にて解析し刺激開始前５分間の平均値（０分値）を１００％とした百分率で表した。なお、データから平均値と標準誤差を計算すると共に、群としての統計学的有意差の検定はANOVA with repeated measuresにより行ない、胃内投与開始前（０分）の神経活動の絶対値間の統計学的有意差の検定はMann-Whitney U-testにより行なった。 The data of these neural activities are analyzed by the average value of the firing frequency per 5 seconds (pulse / 5s) every 5 minutes, and expressed as a percentage with the average value (0 minute value) for 5 minutes before the start of stimulation as 100%. did. The mean value and standard error are calculated from the data, and the statistical significance of the group is tested by ANOVA with repeated measures. Statistics between the absolute values of nerve activity before the start of intragastric administration (0 min) The test of the clinical significance was performed by Mann-Whitney U-test.
肩甲間褐色脂肪組織交感神経活動（brown adipose tissue sympathetic nerve activity、BAT-SNA）および、副睾丸白色脂肪組織交感神経活動（white adipose tissue sympathetic nerve activity、WAT-SNA）についての結果を図６に示す。図６に示すとおり、β−ユーデスモールＣＭＣ水溶液を胃内投与した群では、BAT-SNAがコントロール投与群に対して高いレベルで保持された。胃内投与開始５分後から９０分後までの間のBAT-SNA値をβ−ユーデスモールＣＭＣ水溶液を投与した群とコントロール投与群との２群で統計学的検討により比較するとβ−ユーデスモールＣＭＣ水溶液を投与した群のBAT-SNA値はコントロール投与群のBAT-SNA値よりも有意に高かった。胃内投与開始前（０分）の神経活動の絶対値間の統計学的有意差はなかった。 Fig. 6 shows the results of brown adipose tissue sympathetic nerve activity (BAT-SNA) and white adipose tissue sympathetic nerve activity (WAT-SNA). Show. As shown in FIG. 6, BAT-SNA was maintained at a higher level than the control administration group in the group in which the β-eudesmol CMC aqueous solution was administered intragastrically. When the BAT-SNA value between 5 minutes and 90 minutes after the start of intragastric administration was compared between the group administered with β-eudesmol CMC aqueous solution and the control administration group by statistical examination, β-you The BAT-SNA value of the group administered with the desmol CMC aqueous solution was significantly higher than the BAT-SNA value of the control administration group. There was no statistically significant difference between absolute values of neural activity before the start of intragastric administration (0 minutes).
また、図６に示すとおり、β−ユーデスモールＣＭＣ水溶液を投与した群では、WAT-SNAはコントロール投与群に対して投与後３０分以降から高いレベルを保持した。胃内投与開始５分後から９０分後までの間のBAT-SNA値をβ−ユーデスモールＣＭＣ水溶液を投与した群とコントロール投与群との２群で統計学的検討により比較するとβ−ユーデスモールＣＭＣ水溶液を投与した群のBAT-SNA値はコントロール投与群のBAT-SNA値よりも有意に高かった。胃内投与開始前（０分）の神経活動の絶対値間の統計学的有意差はなかったことから、試験に使用した動物の個体差による影響はないと考えられた。 Further, as shown in FIG. 6, in the group administered with the β-eudesmol CMC aqueous solution, WAT-SNA maintained a high level from 30 minutes after the administration on the control administration group. When the BAT-SNA value between 5 minutes and 90 minutes after the start of intragastric administration was compared between the group administered with β-eudesmol CMC aqueous solution and the control administration group by statistical examination, β-you The BAT-SNA value of the group administered with the desmol CMC aqueous solution was significantly higher than the BAT-SNA value of the control administration group. Since there was no statistically significant difference between the absolute values of nerve activity before the start of intragastric administration (0 minutes), it was considered that there was no effect due to individual differences in the animals used in the study.
［５．β-ユーデスモール投与時の体脂肪増加抑制作用］
β-ユーデスモールによる食欲増進作用及び体脂肪増加抑制作用をより直接検証するため、体脂肪増加抑制作用の検証に汎用されるマウス高脂肪食肥満モデル試験を実施した。
[5. Body fat increase inhibitory effect when β-eudesmol is administered]
In order to directly verify the appetite enhancing action and the body fat increase inhibitory action by β-eudesmol, a mouse high fat diet obesity model test widely used for the verification of the body fat increase inhibiting action was conducted.
「試験方法」
５週齢の雌性Ｃ５７ＢＬ／６Jマウス（日本チャールズリバー）をＡＩＮ９３Ｇ飼料（オリエンタル酵母）により７日間自由飲水、自由摂餌下で飼育後、試験を開始した。試験食には、脂質由来のエネルギー比が６０％の高脂肪食（Metabolism,45,1539-1546(1996)）を用い、β−ユーデスモールＣＭＣ水溶液を給水した。対照群には同様の高脂肪食を与え、β−ユーデスモールを含まないＣＭＣ水溶液を与えた。各群はｎ＝８とし、試験開始時の体重の平均値をもとに群わけを行い３９日間の飼育試験を行った。飼育期間中は一週間に２回の摂餌量の測定、体重測定を行った。飼育最終日に２０時間の絶食条件化でエーテル麻酔の後、頚椎脱臼による安楽死を行った。その後、解剖を行い、精巣周囲脂肪組織、腎周囲脂肪組織、腸間膜周囲脂肪組織をそれぞれ採取し、湿重量を測定した。
"Test method"
Five-week-old female C57BL / 6J mice (Nippon Charles River) were bred with AIN93G diet (Oriental yeast) for 7 days under free drinking and free feeding, and then the test was started. A high fat diet (Metabolism, 45, 1539-1546 (1996)) with a lipid-derived energy ratio of 60% was used as a test diet, and a β-eudesmol CMC aqueous solution was supplied. The control group was given a similar high fat diet and was given an aqueous CMC solution without β-eudesmol. Each group was set to n = 8, divided into groups based on the average body weight at the start of the test, and a 39-day feeding test was conducted. During the breeding period, food intake and body weight were measured twice a week. Euthanasia by cervical dislocation was performed after ether anesthesia under fasting conditions for 20 hours on the last day of breeding. Thereafter, dissection was performed, and peritesticular adipose tissue, perirenal adipose tissue, and perimesenteric adipose tissue were collected, and wet weight was measured.
（結果）
結果を、図７に示す。図中において、対照群はＨＦＤ、β−ユーデスモールＣＭＣ水溶液摂取群はβ-Ｅｕｄと示す。飼育期間中の総摂餌量はβ−ユーデスモールＣＭＣ水溶液の投与によって増加する一方で、体重の増加率はβ−ユーデスモールＣＭＣ水溶液摂餌によって抑制された。更に、解剖時脂肪組織重量は精巣周囲、腎周囲、腸間膜周囲のいずれにおいても、β−ユーデスモールＣＭＣ水溶液摂取群において対照群に対して増加が抑制された。
(result)
The results are shown in FIG. In the figure, the control group is shown as HFD, and the β-eudesmol CMC aqueous solution intake group is shown as β-Eud. While the total food intake during the breeding period was increased by administration of the β-eudesmol CMC aqueous solution, the rate of increase in body weight was suppressed by the β-eudesmol CMC aqueous solution feeding. Furthermore, the increase in adipose tissue weight at the time of dissection was suppressed compared with the control group in the β-eudesmol CMC aqueous solution ingestion group in any of the periphery of the testis, the periphery of the kidney, and the periphery of the mesentery.
以上で示された効果、すなわち体熱産生を制御するBAT-SNAを上昇させる効果、脂肪分解を制御するWAT-SNAを上昇させる効果は、β−ユーデスモールがこれらの神経活動の上昇を介して脂肪分解を促進し体熱産生を上昇させることにより、摂食量の増加による体脂肪増加や体重増加を抑制する効果を有することを示すものである。 The effects shown above, ie, the effect of increasing BAT-SNA that controls body heat production, and the effect of increasing WAT-SNA that controls lipolysis, are due to the increase of these neuronal activities by β-eudesmol. It shows that it has the effect of suppressing body fat increase and body weight increase due to increased food intake by promoting lipolysis and increasing body heat production.
以上の結果から、β−ユーデスモールには味覚的な忌避性がないことを確認し、その摂取は食欲増進をもたらすことにより摂食量を増加させ、かつ摂食量の上昇による体脂肪増加を抑制し、体重の過剰な増加を抑制する手段であることが示された。 From the above results, we confirmed that β-eudesmol has no taste repellency, and its intake increases appetite by increasing appetite and suppresses increase in body fat due to increased intake It has been shown to be a means of suppressing an excessive increase in body weight.
本発明は、容易かつ簡便に香味上優れた状態で摂取でき、安全かつ効果的に食欲を増進しつつ、体重の過剰な増加をもたらさない食欲増進剤を提供する。また、本発明は、食欲増進剤による食欲増進作用に対して、体重増加を抑制することから、該食欲増進作用に対する体重増加抑制剤を提供する。更に、本発明は、食欲増進剤による食欲増進作用に対して、体脂肪増加を抑制することから、該食欲増進作用に対する体脂肪増加抑制剤を提供する。 The present invention provides an appetite enhancer that can be ingested easily and simply in an excellent state of flavor and that promotes appetite safely and effectively, while not causing an excessive increase in body weight. Moreover, since this invention suppresses a body weight increase with respect to the appetite increase effect | action by an appetite enhancer, the weight increase inhibitor with respect to this appetite increase effect | action is provided. Furthermore, since this invention suppresses an increase in body fat with respect to the appetite increase action by an appetite enhancer, the body fat increase inhibitor with respect to this appetite increase action is provided.
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