JP6281919B2 - Pharmaceutical composition, food / beverage composition or food / beverage additive for reducing palatability for high fat food - Google Patents
Pharmaceutical composition, food / beverage composition or food / beverage additive for reducing palatability for high fat food Download PDFInfo
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- 239000000203 mixture Substances 0.000 title claims description 15
- 235000013361 beverage Nutrition 0.000 title claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 8
- 235000019629 palatability Nutrition 0.000 title claims description 5
- 239000000654 additive Substances 0.000 title description 6
- 230000000996 additive effect Effects 0.000 title description 6
- 235000009200 high fat diet Nutrition 0.000 claims description 33
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 claims description 24
- 229950009215 phenylbutanoic acid Drugs 0.000 claims description 11
- 239000004480 active ingredient Substances 0.000 claims description 5
- 235000021329 brown rice Nutrition 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims 1
- FODTZLFLDFKIQH-FSVGXZBPSA-N gamma-Oryzanol (TN) Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)O[C@@H]2C([C@@H]3CC[C@H]4[C@]5(C)CC[C@@H]([C@@]5(C)CC[C@@]54C[C@@]53CC2)[C@H](C)CCC=C(C)C)(C)C)=C1 FODTZLFLDFKIQH-FSVGXZBPSA-N 0.000 description 11
- 235000021590 normal diet Nutrition 0.000 description 8
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- 239000004278 EU approved seasoning Substances 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000209094 Oryza Species 0.000 description 1
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- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical group COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 description 1
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- 230000035764 nutrition Effects 0.000 description 1
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- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
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- 239000000843 powder Substances 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000008165 rice bran oil Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
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- 235000021076 total caloric intake Nutrition 0.000 description 1
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 description 1
Images
Description
本発明は、高脂肪食への嗜好性を軽減させるための医薬組成物、飲食品組成物または飲食品添加剤に関するものである。 The present invention relates to a pharmaceutical composition, a food / beverage composition, or a food / beverage additive for reducing the preference for a high-fat food.
近年、世界中で肥満症が急増しており、その予防と克服が社会的、医療経済的に強く求められている。病態や発症機序の解明も進みつつあり、多くの治療薬が開発されてきたが、副作用や不十分な臨床効果などの問題を抱え、未だ広く普及するに至っていない。 In recent years, obesity has been rapidly increasing all over the world, and the prevention and overcoming thereof are strongly demanded socially and medically economically. Elucidation of the pathology and onset mechanism is also progressing, and many therapeutic drugs have been developed. However, they have problems such as side effects and insufficient clinical effects, and have not yet spread widely.
このような背景を踏まえ、安全性の高い天然食品由来で有効な抗肥満作用を発揮する物質の探索が求められている。本発明者らは、玄米摂取により、被検体の高脂肪食への嗜好性を軽減させることを明らかにしてきた（非特許文献１〜３）。しかしながら、玄米由来成分中の、被検体の高脂肪食への嗜好性を軽減させる分子実体は知られていなかった。 Based on such a background, search for a substance that exhibits an effective anti-obesity action derived from a highly safe natural food is required. The present inventors have clarified that brown rice intake reduces the subject's preference for a high fat diet (Non-Patent Documents 1 to 3). However, a molecular entity that reduces the preference of a subject to a high-fat diet in brown rice-derived components has not been known.
玄米由来成分の１つであるγ−オリザノールには、抗肥満効果や、抗糖尿病効果が知られている（特許文献１および２）。しかし、高脂肪食への嗜好性に対する影響については、今日まで何らの知見も得られていなかった。 An anti-obesity effect and an anti-diabetic effect are known for γ-oryzanol, which is one of the components derived from brown rice (Patent Documents 1 and 2). However, until now, no knowledge has been obtained about the influence on palatability for a high fat diet.
本発明は、高脂肪食への嗜好性を軽減させるための医薬組成物、飲食品組成物または飲食品添加剤を提供する。 The present invention provides a pharmaceutical composition, a food / beverage composition, or a food / beverage additive for reducing the preference for a high-fat food.
本発明者は、４−フェニル酪酸またはγ−オリザノールが、高脂肪食への嗜好性を軽減させることを、初めて見出し、本発明を完成させた。 The present inventor found for the first time that 4-phenylbutyric acid or γ-oryzanol reduces the preference for high-fat foods, and completed the present invention.
すなわち、本発明は以下のとおりである。
［１］ ４−フェニル酪酸またはγ−オリザノールを含む、高脂肪食への嗜好性を軽減させるための医薬組成物、飲食品組成物または飲食品添加剤、
に関する。
That is, the present invention is as follows.
[1] A pharmaceutical composition, a food / beverage composition or a food / beverage additive for reducing the preference for a high fat diet, comprising 4-phenylbutyric acid or γ-oryzanol,
About.
本発明の、４−フェニル酪酸またはγ−オリザノールを含む医薬組成物、飲食品組成物または飲食品添加剤により、高脂肪食への嗜好性を軽減させ、無意識のうちに低脂肪食をたべるようになり、肥満防止その他成人病防止にも大いに効果がある。 The pharmaceutical composition, the food / beverage product composition or the food / beverage product additive containing 4-phenylbutyric acid or γ-oryzanol according to the present invention reduces the preference for a high-fat food and allows the user to eat a low-fat food unconsciously. Therefore, it is very effective in preventing obesity and other adult diseases.
定義
本明細書において使用する「γ−オリザノール」という用語は、米ぬか油、米胚芽油等に特有の生理活性物質であり、フェルラ酸に数種類のトリペルテンアルコールがエステル結合した物質の混合物の総称を指す。
Definitions As used herein, the term “γ-oryzanol” is a physiologically active substance unique to rice bran oil, rice germ oil, etc., and is a general term for a mixture of substances in which several types of triperten alcohol are ester-bonded to ferulic acid. Point to.
本明細書において使用する「高脂肪食」という用語は、脂肪分の割合がカロリー比率で通常食よりも高い、任意の食餌を指す。本明細書において使用する通常食の脂肪分は、１０〜１５％の範囲である。従って、高脂肪食においては脂肪分の割合は１５％よりも多く、好ましくは３０〜７０％の範囲であり、肥満者の食生活の実態を考慮すると、４０〜５０％がより好ましい範囲である。 As used herein, the term “high fat diet” refers to any diet in which the percentage of fat is higher in calories than the normal diet. As used herein, the fat content of a normal diet ranges from 10 to 15%. Therefore, in a high fat diet, the proportion of fat is more than 15%, preferably in the range of 30 to 70%, and considering the actual diet of obese people, 40 to 50% is a more preferable range. .
本明細書において使用する「高脂肪食への嗜好性」という用語は、任意の複数の食餌を同時に与えた際に、一週間当たりの摂食量全体に対する、高脂肪食の摂食量の割合を示す。本明細書において、高脂肪食への嗜好性を、以下の式によって定義する：
高脂肪食への嗜好性（％）＝［（高脂肪食の摂食量（ｇ／ｗｅｅｋ））／（（通常食の摂食量（ｇ／ｗｅｅｋ））＋（高脂肪食の摂食量（ｇ／ｗｅｅｋ）））］×１００。
即ち、この値が５０より高ければ高脂肪食を通常食よりも多く摂取していることを示し、５０より低ければ通常食の摂取が多いということを定量的に示すことが出来る。
As used herein, the term “preference for a high-fat diet” refers to the ratio of high-fat diet intake to the total intake per week when any multiple diets are given simultaneously. . Herein, palatability for a high fat diet is defined by the following formula:
Preference for high fat diet (%) = [(high fat diet intake (g / weak)) / ((normal diet intake (g / weak)) + (high fat diet intake (g / week)))] × 100.
That is, if this value is higher than 50, it can be shown that a high fat diet is consumed more than a normal diet, and if it is less than 50, it can be quantitatively shown that a normal diet is consumed more.
本明細書において使用する「軽減させる」という用語は、任意の介入が、高脂肪食への嗜好性を、介入しない場合に比べて有意差をもって低下させることを指す。本明細書においては、Ｓｔｕｄｅｎｔのｔ検定により有意水準Ｐ＜０．０５で有意差がある場合に、該介入が、高脂肪食への嗜好性を軽減させるという。 As used herein, the term “reduce” refers to any intervention that significantly reduces the preference for a high fat diet compared to no intervention. In this specification, it is said that the intervention reduces the preference for a high fat diet when there is a significant difference at the significance level P <0.05 by Student's t test.
本発明に係る組成物は、食品として、特に高脂肪食への嗜好性の軽減の目的で健康食品、機能性食品、健康補助食品、特定保健用食品として使用することができる。これら食品は、例えばお茶、ジュースといった飲料水；ゼリー、あめ、チョコレート、チューインガムなどの形態であってもよい。また、本発明に係る食品は、栄養補助食品（サプリメント）として、液剤、粉剤、粒剤、カプセル剤、錠剤の形で製造されてもよい。 The composition according to the present invention can be used as a food, in particular, as a health food, a functional food, a health supplement, or a food for specified health use for the purpose of reducing the preference for a high fat diet. These foods may be in the form of drinking water such as tea and juice; jelly, candy, chocolate, chewing gum and the like. Moreover, the foodstuff which concerns on this invention may be manufactured in the form of a liquid agent, a powder agent, a granule, a capsule, and a tablet as a dietary supplement (supplement).
さらに本発明の飲食品組成物には、必要に応じて本発明の効果を損なわない範囲で、通常用いるところの各種成分を配合することができる。例えば賦形剤、結合剤、増粘剤、乳化剤、着色料、香料、食品添加物、調味料等の成分を配合することができる。 Furthermore, the various components used normally can be mix | blended with the food-drinks composition of this invention in the range which does not impair the effect of this invention as needed. For example, components such as excipients, binders, thickeners, emulsifiers, colorants, fragrances, food additives, and seasonings can be blended.
また、本発明に係る組成物は、医薬として、例えば、高脂肪食への嗜好性の治療または予防に使用することができる。これら医薬品は、例えば錠剤、コーティング錠、糖衣錠、硬もしくは軟ゼラチンカプセル剤、液剤、乳濁剤又は懸濁剤の形態で経口的に投与することができるが、例えば座剤の形態で直腸的に；例えば軟膏、クリーム剤、ゲル剤又は液剤の形態で局部的又は経皮的に；例えば注射用液剤として非経口的に投与することもできる。 Moreover, the composition which concerns on this invention can be used as a pharmaceutical for the treatment or prevention of the palatability to a high fat diet, for example. These medicaments can be administered orally, for example in the form of tablets, coated tablets, dragees, hard or soft gelatin capsules, solutions, emulsions or suspensions, eg rectally in the form of suppositories. It can also be administered locally or transdermally, for example in the form of an ointment, cream, gel or solution; for example parenterally as an injectable solution.
さらに本発明の医薬組成物には、必要に応じて本発明の効果を損なわない範囲で、通常用いるところの各種担体を配合することができる。例えば賦形剤、結合剤、崩壊剤、滑沢剤、流動化剤、着色剤、可塑剤等の担体を配合することができる。 Furthermore, in the pharmaceutical composition of the present invention, various carriers that are usually used can be blended as needed within a range not impairing the effects of the present invention. For example, carriers such as an excipient, a binder, a disintegrant, a lubricant, a fluidizing agent, a colorant, and a plasticizer can be blended.
医薬として、本発明に係る組成物の投与量は、特に制限されないが、投与経路、剤型、患者の年齢、体重および症状に応じて適宜選択することができる。例えば、経口投与の場合には、成人１日当り有効成分量として１ｍｇ〜１００ｇの投与が望ましい。また、投与期間は、年齢、症状に応じて任意に定めることができる。 The dosage of the composition according to the present invention is not particularly limited as a pharmaceutical, but can be appropriately selected according to the administration route, dosage form, patient age, weight and symptoms. For example, in the case of oral administration, it is desirable to administer 1 mg to 100 g as an active ingredient amount per day for an adult. The administration period can be arbitrarily determined according to age and symptoms.
以下、実施例によって、本発明の組成物を更に詳細に説明するが、本発明はその趣旨と適用範囲に逸脱しない限りこれらに限定されるものではない。 Hereinafter, the composition of the present invention will be described in more detail by way of examples. However, the present invention is not limited to these without departing from the spirit and scope of application.
［実施例１］
４−ＰＢＡによる高脂肪食嗜好性の軽減
材料および方法
動物は８週齢の雄性Ｃ５７ＢＬ／６Ｊマウス（日本チャールズ・リバー株式会社、神奈川）を使用した。１ケージあたり２匹のマウスを飼育し、１つの条件に対し３ケージ用いた。４−フェニル酪酸（４−ＰＢＡ）（和光純薬工業株式会社、大阪）を、等モル量の水酸化ナトリウムで溶解してｐＨ７．４に調整後、ＰＢＳで希釈し、ｇ体重あたり１２０μｇで１日１回８週間連日腹腔内投与した。高脂肪食への嗜好性は、通常食（脂肪分１０％、Ｄ１２４５０Ｂ、Research Diet、New Brunswick, NJ, USA）と高脂肪食（脂肪分４５％、Ｄ１２４５１、Research Diet、New Brunswick, NJ, USA）を同時に給餌することによりマウスが両者を自由に選択できる条件下で飼育し、１ケージあたりの通常食と高脂肪食それぞれの摂食量を１週間毎に測定して、週ごとに評価した。
結果
結果を図１に示す。投与後２週目、３週目、４週目において、対照群では高脂肪食への嗜好性がそれぞれ、９９．６％、９９．５％、９９．４％であったのに対し、４−ＰＢＡ投与群ではそれぞれ９８．９％、９８．４％、９８．３％であった。これは、４−ＰＢＡが、対照群に比べて２．６倍〜３．４倍、高脂肪食への嗜好性を明らかに軽減させることを意味する。
[Example 1]
Material and method for reducing high fat diet preference with 4-PBA As animals, 8-week-old male C57BL / 6J mice (Nippon Charles River Co., Ltd., Kanagawa) were used. Two mice were bred per cage, and 3 cages were used for one condition. 4-Phenylbutyric acid (4-PBA) (Wako Pure Chemical Industries, Ltd., Osaka) was dissolved in an equimolar amount of sodium hydroxide to adjust to pH 7.4, diluted with PBS, and 1 at 120 μg per g body weight. It was intraperitoneally administered once a day for 8 weeks every day. The preference for high-fat diets includes normal diet (10% fat, D12450B, Research Diet, New Brunswick, NJ, USA) and high-fat diet (45% fat, D12451, Research Diet, New Brunswick, NJ, USA). ) At the same time, the mice were reared under conditions where both could be freely selected, and the amount of each normal diet and high fat diet per cage was measured every week and evaluated weekly.
Results The results are shown in FIG. At 2 weeks, 3 weeks and 4 weeks after administration, the preference for high fat diet was 99.6%, 99.5% and 99.4% in the control group, respectively. -In the PBA administration group, they were 98.9%, 98.4%, and 98.3%, respectively. This means that 4-PBA clearly reduces the preference for high fat diets by 2.6 to 3.4 times compared to the control group.
［実施例２］
γ−オリザノールによる高脂肪食嗜好性の軽減
材料および方法
動物は８週齢の雄性Ｃ５７ＢＬ／６Ｊマウス（（日本チャールズ・リバー株式会社、神奈川）を使用した。１ケージあたり２匹のマウスを飼育し、１つの条件に対し３ケージ用いた。γ−オリザノール（和光純薬工業株式会社、大阪）を、０．５％メチルセルロース溶液（133-14255、和光純薬工業株式会社、大阪）に懸濁し、ゾンデを用いてｇ体重あたり８０μｇで１日１回８週間連日経口投与した。高脂肪食への嗜好性は、通常食（脂肪分１０％、Ｄ１２４５０Ｂ、Research Diet、New Brunswick, NJ, USA）と高脂肪食（脂肪分４５％、Ｄ１２４５１、Research Diet、New Brunswick, NJ, USA）を同時に給餌することによりマウスが両者を自由に選択できる条件下で飼育し、１ケージあたりの通常食と高脂肪食それぞれの摂食量を１週間毎に測定して、週ごとに評価した。
結果
結果を図２に示す。投与後５週目、６週目、７週目において、対照群では高脂肪食への嗜好性がそれぞれ、９８．５％、９８．５％、９８．３％であったのに対し、γ−オリザノール投与群ではそれぞれ９７．８％、９７．６％、９７．５％であった。これは、γ−オリザノールが、対照群に比べて１．４倍〜１．５倍、高脂肪食への嗜好性を明らかに軽減させることを意味する。
[Example 2]
Materials and methods for reducing high fat diet preference with γ-oryzanol The animals used were 8-week-old male C57BL / 6J mice (Nippon Charles River Co., Ltd., Kanagawa). Three cages were used for one condition: γ-oryzanol (Wako Pure Chemical Industries, Ltd., Osaka) was suspended in a 0.5% methylcellulose solution (133-14255, Wako Pure Chemical Industries, Ltd., Osaka), Using a sonde, it was orally administered once a day for 8 weeks once a day at 80 μg per g body weight.The preference for high-fat diet was as follows: normal diet (10% fat, D12450B, Research Diet, New Brunswick, NJ, USA) By feeding a high fat diet (fat content 45%, D12451, Research Diet, New Brunswick, NJ, USA) at the same time, the mice are reared under conditions that allow them to freely select both.肪食 each of the food intake was measured every week, it was evaluated on a weekly basis.
Results The results are shown in FIG. At 5 weeks, 6 weeks, and 7 weeks after administration, the preference for the high fat diet was 98.5%, 98.5%, and 98.3% in the control group, respectively. -In the oryzanol administration group, they were 97.8%, 97.6%, and 97.5%, respectively. This means that γ-oryzanol clearly reduces the preference for high fat diets by 1.4 to 1.5 times compared to the control group.
本発明の、４−フェニル酪酸またはγ−オリザノールを含む医薬組成物、飲食品組成物または飲食品添加剤は、上記で述べたように、高脂肪食への嗜好性を軽減させるのに有用である。総摂取カロリーに占める脂肪分の割合が急速に増加している現代日本人における実態からみて本発明は、学術的にも有用である。 The pharmaceutical composition, food / beverage product composition or food / beverage product additive containing 4-phenylbutyric acid or γ-oryzanol of the present invention is useful for reducing the preference for a high-fat food, as described above. is there. The present invention is also academically useful from the viewpoint of the actual situation in modern Japanese in which the proportion of fat in the total calorie intake is rapidly increasing.
Claims (4)
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