JP2021155419A - Composition for lipase activity inhibition - Google Patents

Composition for lipase activity inhibition Download PDF

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JP2021155419A
JP2021155419A JP2021053944A JP2021053944A JP2021155419A JP 2021155419 A JP2021155419 A JP 2021155419A JP 2021053944 A JP2021053944 A JP 2021053944A JP 2021053944 A JP2021053944 A JP 2021053944A JP 2021155419 A JP2021155419 A JP 2021155419A
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ecklonia
kurome
extract
hours
water
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JP7036395B2 (en
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寿梓 八木
Hisashi Yagi
寿梓 八木
慎太郎 正壽
Shintaro Masatoshi
慎太郎 正壽
佑夏 伊藤
Yuka Ito
佑夏 伊藤
明日香 三輪
Asuka Miwa
明日香 三輪
紀子 網城
Noriko Amishiro
紀子 網城
隆 大城
Takashi Oshiro
隆 大城
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Rohto Pharmaceutical Co Ltd
Tottori University NUC
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Tottori University NUC
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Abstract

To reveal the health benefits of Ecklonia kurome and to provide compositions that can be used in foods and the like.SOLUTION: Provided is a composition for lipase activity inhibition, lipid absorption inhibition, stool slippage improvement, or intestinal regulation, which contains an effective amount of the water extract of Ecklonia kurome (scientific name: Ecklonia kurome). Provided is a method for producing the water extract or processed product of Ecklonia kurome, comprising the following step: (1) extracting Ecklonia kurome with hot water at 50 to 80°C for 1 to 5 hours.SELECTED DRAWING: Figure 1

Description

カジメ属クロメ(学名:Ecklonia kurome)は、レッソニア科カジメ属の褐藻の1種であり、日本近海では本州太平洋岸の中南部から九州、瀬戸内海、日本海岸にかけて分布しており、海外では、韓国の済州島等にて分布することが確認されている。成体での大きさは、通常20〜50cmである。 Ecklonia cava (scientific name: Ecklonia cava) is a type of brown alga of the genus Ecklonia cava in the family Ecklonia cava. It has been confirmed that it is distributed on Ecklonia cava, etc. The adult size is usually 20-50 cm.

形態が類似する種としては、カジメやアラメが知られているが、カジメは葉部にシワが入らない点、アラメは茎上部で二叉に分かれる点で、クロメと区別される。 Ecklonia cava and Ecklonia cava are known as species with similar morphology, but Ecklonia cava is distinguished from Ecklonia cava in that it does not wrinkle in the leaves and arame is bifurcated at the upper part of the stem.

クロメは、主に冬季に収穫される藻体が食用されており、大分県の佐賀関などの一地域においては特産品として、刻んだ生クロメのほか、調味料(醤油、ソース等)や加工食品に利用されている。クロメは、アミノ酸やミネラル分が豊富であり、健康効果も期待される。 Ecklonia kurome is mainly eaten by algae harvested in winter, and in some areas such as Saganoseki in Oita prefecture, as a special product, in addition to chopped raw kurome, seasonings (soy sauce, sauce, etc.) and processing It is used in food. Chrome is rich in amino acids and minerals and is expected to have health benefits.

しかしながら、日本全体でみると、他の海産物の収穫に付随して得られたクロメは廃棄されており、活用が充分なされている食材とは言い難い。このような状況に対して、クロメの食用としての価値の高さから養殖技術の開発が進められている(非特許文献1、2)。 However, looking at Japan as a whole, the chrome obtained from the harvest of other marine products is discarded, and it cannot be said that it is a fully utilized foodstuff. In response to this situation, the development of aquaculture technology is being promoted due to the high value of Ecklonia kurome as an edible product (Non-Patent Documents 1 and 2).

西垣友和ら著、「若狭湾西部海域における褐藻クロメの分布特性および季節的消長」京都府農林水産技術センター海洋センター研究報告、第37号、2015、P.1−6Tomokazu Nishigaki et al., "Distribution characteristics and seasonal fate of brown algae kurome in the western waters of Wakasa Bay," Kyoto Prefectural Agriculture, Forestry and Fisheries Technology Center Marine Center Research Report, No. 37, 2015, P.M. 1-6 西垣友和ら著、「京都府蒲入地先における養殖クロメの生長と形態」京都府立海洋センター研究報告、第28号、2006、P.16−20Tomokazu Nishigaki et al., "Growth and Morphology of Cultured Ecklonia kurome in Kamanyu, Kyoto Prefecture," Kyoto Prefectural Marine Center Research Report, No. 28, 2006, P.M. 16-20 上野浩晶ら著、「新たに登場する抗肥満薬の動向と展望」日本内科学会雑誌、第103巻、第3号、2014、P.753−759Hiroaki Ueno et al., "Trends and Prospects of New Anti-Obesity Drugs", Journal of the Japanese Society of Internal Medicine, Vol. 103, No. 3, 2014, P.M. 753-759

上述の通り、クロメは廃棄されることが多い海藻であり、食品等において未だ充分な活用はなされておらず、クロメの健康効果についても、詳細な検討や研究報告が殆ど無い。 As mentioned above, Ecklonia kurome is a seaweed that is often discarded, and has not yet been fully utilized in foods, etc., and there are few detailed studies or research reports on the health effects of Ecklonia kurome.

そこで、本発明は、クロメの健康効果を明らかにし、食品等において利用可能な組成物を提供することを目的とする。 Therefore, an object of the present invention is to clarify the health effect of Ecklonia kurome and to provide a composition that can be used in foods and the like.

上記課題を解決するために、本発明者等が鋭意検討した結果、クロメの水抽出物には、顕著なリパーゼ活性阻害を有することを見出し、本発明を完成するに至った。 As a result of diligent studies by the present inventors in order to solve the above problems, it was found that the water extract of Ecklonia kurome has a remarkable inhibition of lipase activity, and the present invention has been completed.

すなわち、本発明は、下記に掲げる組成物を提供する。
[1]
カジメ属クロメ(学名:Ecklonia kurome)の水抽出物を有効量含有する、リパーゼ活性阻害用組成物。
That is, the present invention provides the compositions listed below.
[1]
A composition for inhibiting lipase activity, which contains an effective amount of a water extract of Ecklonia kurome (scientific name: Ecklonia kurome).

[2]
カジメ属クロメ(学名:Ecklonia kurome)の水抽出物を有効量含有する、脂質吸収抑制用、便の滑り向上用、又は整腸用組成物。
[2]
A composition for suppressing lipid absorption, improving stool slippage, or intestinal regulation, which contains an effective amount of a water extract of Ecklonia kurome (scientific name: Ecklonia kurome).

[3]
前記カジメ属クロメが、クロメの乾燥物である、[1]又は[2]に記載の組成物。
[3]
The composition according to [1] or [2], wherein the Ecklonia cava genus Ecklonia cava is a dried product of Ecklonia cava.

[4]
前記カジメ属クロメの抽出部位が、葉体、及び/又は、茎である、[1]〜[3]のいずれか1に記載の組成物。
[4]
The composition according to any one of [1] to [3], wherein the extraction site of Ecklonia cava is a frond and / or a stem.

[5]
前記カジメ属クロメの生育期間が、1年〜6年である、[1]〜[4]のいずれか1に記載の組成物。
[5]
The composition according to any one of [1] to [4], wherein the Ecklonia cava has a growth period of 1 to 6 years.

[6]
前記抽出物を得るための抽出温度が、50〜80℃である、[1]〜[5]のいずれか1に記載の組成物。
[6]
The composition according to any one of [1] to [5], wherein the extraction temperature for obtaining the extract is 50 to 80 ° C.

[7]
前記抽出物を得るための抽出時間が、1〜5時間である、[1]〜[6]のいずれか1に記載の組成物。
[7]
The composition according to any one of [1] to [6], wherein the extraction time for obtaining the extract is 1 to 5 hours.

[8]
医薬品、医薬部外品、化粧品、又は、飲食品である、[1]〜[7]のいずれか1に記載の組成物。
[8]
The composition according to any one of [1] to [7], which is a drug, a quasi drug, a cosmetic product, or a food or drink.

[9]
1日摂取量が、乾燥固形分換算にて、500mg以上である、[1]〜[8]のいずれか1に記載の組成物。
[9]
The composition according to any one of [1] to [8], wherein the daily intake is 500 mg or more in terms of dry solid content.

また、本発明は、下記に掲げる製造方法を提供する。
[10]
以下の工程:
(1)カジメ属クロメを、50〜80℃の熱水により、1〜5時間抽出する工程を含む、カジメ属クロメの水抽出物又は加工品の製造方法。
The present invention also provides the following manufacturing methods.
[10]
The following steps:
(1) A method for producing an aqueous extract or processed product of Ecklonia cava, which comprises a step of extracting Ecklonia cava with hot water at 50 to 80 ° C. for 1 to 5 hours.

[11]
脂質吸収抑制作用が高められてなるカジメ属クロメの水抽出物又は加工品である、[10]に記載の方法。
[11]
The method according to [10], which is a water extract or processed product of Ecklonia cava, which has an enhanced lipid absorption inhibitory effect.

また、本発明は、下記に掲げるカジメ属クロメの加工品を提供する。 The present invention also provides the following processed products of the genus Ecklonia cava.

[12]
カジメ属クロメ(学名:Ecklonia kurome)の水抽出物を有効量含有し、
該抽出物を得るための抽出温度が、50〜80℃であり、
該抽出物を得るための抽出時間が、1〜5時間である、
カジメ属クロメの加工品。
[12]
Contains an effective amount of a water extract of Ecklonia kurome (scientific name: Ecklonia kurome),
The extraction temperature for obtaining the extract is 50 to 80 ° C.
The extraction time to obtain the extract is 1-5 hours.
Processed product of Ecklonia cava.

本発明によれば、食品等において利用可能なクロメの水抽出物による、リパーゼ活性阻害用、脂質吸収抑制用、便の滑り向上用、又は整腸用の組成物を提供することが可能となる。 According to the present invention, it is possible to provide a composition for inhibiting lipase activity, suppressing lipid absorption, improving stool slippage, or intestinal regulation by using a water extract of Ecklonia kurome that can be used in foods and the like. ..

図1は、試験例2における、各温度・抽出時間から得られたクロメの水抽出物(被験試料)のリパーゼ活性阻害試験の結果を示すグラフである。FIG. 1 is a graph showing the results of a lipase activity inhibition test of a water extract (test sample) of Ecklonia kurome obtained from each temperature and extraction time in Test Example 2.

[リパーゼ活性阻害用組成物]
本発明において、リパーゼ活性阻害用組成物は、カジメ属クロメ(学名:Ecklonia kurome)の水抽出物を有効量含有する。
[Composition for Inhibiting Lipase Activity]
In the present invention, the composition for inhibiting lipase activity contains an effective amount of a water extract of Ecklonia kurome (scientific name: Ecklonia kurome).

クロメは、レッソニア科カジメ属の褐藻の1種である。本発明において、適用可能なクロメの部位は、本発明の効果を奏する限りにおいて限定はされないが、例えば、葉体、茎(中芯)、及び、芽株からなる群より選択される少なくとも1種が挙げられ、葉体、及び/又は、茎が好ましい。 Ecklonia kurome is a species of brown alga of the genus Ecklonia cava in the family Ecklonia cava. In the present invention, the applicable chrome site is not limited as long as the effect of the present invention is exhibited, but at least one selected from the group consisting of, for example, fronds, stems (core), and buds. The fronds and / or stems are preferred.

クロメは、日本近海では本州太平洋岸の中南部から九州、瀬戸内海、日本海岸に広く分布しており、海外では、韓国の済州島等にて分布することが確認されている。一般に海藻は、海流の強さ、水温、海底の高さ等により、海藻の生育や栄養成分の量が異なってくる。クロメの産地は、本発明の効果を奏する限りにおいて限定はされないが、例えば、鳥取県産、大分県産、熊本県産、愛媛県産、愛知県産等が挙げられ、鳥取県産、大分県産、又は、熊本県産が好ましく、鳥取県産、又は、大分県産がより好ましく、鳥取県産が特に好ましい。ここで、各都道府県産というのは、県が管理する海域(港湾区域、漁港区域、一般海域)又は海岸(海岸保全区域、一般公共海岸区域)のいずれかで収穫できるものを言う。限定はされないが、本願発明の効果を顕著に奏する観点から、クロメの採取時期は、鳥取県産クロメの場合、例えば、2月〜8月が好ましく、4月〜6月がより好ましい。 Kurome is widely distributed in the waters near Japan from the central and southern part of the Pacific coast of Honshu to Kyushu, the Seto Inland Sea, and the coast of Japan, and overseas, it has been confirmed that it is distributed on Jeju Island in South Korea. In general, the growth of seaweed and the amount of nutritional components of seaweed differ depending on the strength of ocean currents, water temperature, height of the seabed, and the like. The production area of Kurome is not limited as long as the effect of the present invention is exhibited, but examples thereof include Tottori prefecture, Oita prefecture, Kumamoto prefecture, Ehime prefecture, Aichi prefecture, etc., Tottori prefecture, Oita prefecture, etc. It is preferably produced in Kumamoto prefecture or Kumamoto prefecture, more preferably produced in Tottori prefecture or Oita prefecture, and particularly preferably produced in Tottori prefecture. Here, the products produced in each prefecture are those that can be harvested in either the sea area (port area, fishing port area, general sea area) or the coast (coastal conservation area, general public coast area) managed by the prefecture. Although not limited, the time for collecting Ecklonia kurome is preferably February to August, and more preferably April to June, for example, in the case of Ecklonia kurome produced in Tottori Prefecture, from the viewpoint of remarkably exerting the effect of the present invention.

クロメは多年草であるが、その生育期間は、本発明の効果を奏する限りにおいて限定されない。クロメの生育期間は、例えば、1年〜6年が好ましく、1年〜5年がより好ましく、1年〜4年が更に好ましく、1年〜3年が特に好ましく、1年〜2年が最も好ましい。クロメの生育期間が1年目のものは、形態が笹の葉状であり、2年目以降は、茎の上部に羽状にのびた葉状部を有する点から、生育期間が1年目〜2年目等のクロメを判別することが可能である。 Although Kurome is a perennial plant, its growing period is not limited as long as the effects of the present invention are exhibited. The growing period of Ecklonia kurome is, for example, preferably 1 to 6 years, more preferably 1 to 5 years, further preferably 1 to 4 years, particularly preferably 1 to 3 years, and most preferably 1 to 2 years. preferable. Ecklonia kurome grows in the first year, and the morphology is bamboo leaf-like. It is possible to discriminate the chrome of the eyes and the like.

クロメの水抽出物は、本発明の効果を奏する限り、常法により水を用いて抽出することで調製され、抽出液であってもよく、その乾燥物であってもよい。 The water extract of Ecklonia kurome is prepared by extracting with water by a conventional method as long as the effect of the present invention is exhibited, and may be an extract or a dried product thereof.

限定はされないが、例えば、クロメを生の状態、乾燥物、又は、粉砕物を、水に浸漬させ、至適な温度条件、及び、時間条件により浸漬抽出することで、クロメの水抽出物を調製することが可能である。限定はされないが、後述の実施例(試験例6)では、クロメの乾燥物を用いることで、より高い本願発明の効果を奏することが確認されている。クロメの乾燥物を得る方法は、特に限定されず、公知の方法が利用でき、例えば、天日干しを行うことや、公知の乾燥機によりクロメの乾燥物を得ること等が挙げられる。天日干しを行う場合は、天候や季節、時間帯等によって条件は異なり、適宜調整され得るが、少なくとも6時間以上、12時間以上、24時間(1日)以上等、天日干しを行うことが挙げられる。乾燥機を用いる場合は、その乾燥条件は特に限定されないが、凍結乾燥、加熱乾燥等が挙げられる。加熱乾燥を行う場合の加熱温度は、例えば、30〜50℃が好ましく、35〜40℃がより好ましい。加熱乾燥を行う場合の加熱時間は、例えば、1〜24時間が好ましく、1〜10時間がより好ましく、1〜5時間が更に好ましい。 Although not limited, for example, a water extract of chrome is obtained by immersing the chrome in a raw state, a dried product, or a pulverized product in water and immersing and extracting the chrome under optimum temperature conditions and time conditions. It is possible to prepare. Although not limited, in Examples (Test Example 6) described later, it has been confirmed that the use of a dried product of Ecklonia kurome exerts a higher effect of the present invention. The method for obtaining the dried product of Ecklonia kurome is not particularly limited, and a known method can be used. Examples thereof include sun-drying and obtaining a dried product of Ecklonia kurome by a known dryer. When sun-drying, the conditions vary depending on the weather, season, time of day, etc. and can be adjusted as appropriate, but it is recommended to sun-dry at least 6 hours or more, 12 hours or more, 24 hours (1 day) or more, etc. Be done. When a dryer is used, the drying conditions are not particularly limited, and examples thereof include freeze-drying and heat-drying. The heating temperature for heat drying is, for example, preferably 30 to 50 ° C, more preferably 35 to 40 ° C. The heating time for heat drying is, for example, preferably 1 to 24 hours, more preferably 1 to 10 hours, and even more preferably 1 to 5 hours.

別の実施形態においては、例えば、クロメを圧搾し、搾汁を得て、圧搾により分離された圧搾粕を水に浸漬させ、至適な温度条件、及び、時間条件により浸漬抽出し、搾汁と抽出物を得たうえで、それぞれを混合してクロメの水抽出物として用いてもよい。 In another embodiment, for example, chrome is squeezed to obtain squeezed juice, the squeezed lees separated by squeezing is immersed in water, and the juice is extracted by immersion under optimum temperature and time conditions. And, after obtaining the extract, each may be mixed and used as a water extract of Kurome.

上記浸漬抽出における温度条件は、本発明の効果を奏する限りにおいて限定はされないが、例えば、常温であってもよく、加熱してもよい。加熱により浸漬抽出を行う場合、抽出温度は、例えば、30〜120℃が好ましく、40〜110℃がより好ましく、50〜90℃が更に好ましく、50〜80℃が更により好ましく、60〜80℃が更により好ましく、60〜75℃が更により好ましく、65〜75℃が更により好ましく、65〜70℃(例えば約70℃)が最も好ましい。 The temperature conditions in the immersion extraction are not limited as long as the effects of the present invention are exhibited, but may be, for example, room temperature or heating. When performing immersion extraction by heating, the extraction temperature is, for example, preferably 30 to 120 ° C, more preferably 40 to 110 ° C, further preferably 50 to 90 ° C, even more preferably 50 to 80 ° C, and 60 to 80 ° C. Is even more preferable, 60 to 75 ° C. is even more preferable, 65 to 75 ° C. is even more preferable, and 65 to 70 ° C. (for example, about 70 ° C.) is most preferable.

上記浸漬抽出における時間条件は、本発明の効果を奏する限りにおいて限定はされないが、抽出時間は、例えば、10分〜24時間が好ましく、30分〜10時間がより好ましく、1時間〜5時間(例えば1時間〜3時間)が更に好ましく、2時間〜4時間(例えば2.5時間〜3.5時間、3時間)が特に好ましい。 The time conditions in the immersion extraction are not limited as long as the effects of the present invention are exhibited, but the extraction time is preferably, for example, 10 minutes to 24 hours, more preferably 30 minutes to 10 hours, and 1 hour to 5 hours (1 hour to 5 hours). For example, 1 hour to 3 hours is more preferable, and 2 hours to 4 hours (for example, 2.5 hours to 3.5 hours, 3 hours) is particularly preferable.

[用途]
本発明のリパーゼ活性阻害用組成物は、生体内で脂質分解酵素(リパーゼ)の活性を阻害する効果を少なくとも有する。リパーゼ活性阻害効果は、後述の実施例に記載の方法により評価することが可能である。
[Use]
The composition for inhibiting lipase activity of the present invention has at least the effect of inhibiting the activity of a lipolytic enzyme (lipase) in vivo. The lipase activity inhibitory effect can be evaluated by the method described in Examples described later.

本発明のリパーゼ活性阻害用組成物は、生体内で脂質分解酵素(リパーゼ)の活性を阻害する効果を発揮することにより、脂質吸収抑制用、内臓脂肪蓄積抑制用、肥満改善用等に用いられる他、整腸用、腸内細菌業改善用、腸内環境改善用等にも好適に用いることができる。 The composition for inhibiting lipase activity of the present invention is used for suppressing lipid absorption, suppressing visceral fat accumulation, improving obesity, etc. by exerting the effect of inhibiting the activity of lipolytic enzyme (lipase) in vivo. In addition, it can be suitably used for intestinal regulation, improvement of intestinal bacterial industry, improvement of intestinal environment, and the like.

また、本発明は、脂質分解が抑制され、体外への脂質排出を促進できることから、便における脂質量を増加させ、排便を促す効果や排便時の便の滑りを向上させるためにも好適に用いることができる。このことは、リパーゼ活性阻害の作用機序を持つ医薬製剤がトリグリセリドの吸収抑制により抗肥満薬として用いられており、排便回数の増加、油性便の増加を伴うといった報告からも明らかである(非特許文献3)。 In addition, since the present invention suppresses lipid decomposition and promotes the excretion of lipids from the body, it is suitably used for increasing the amount of lipids in stool, promoting the effect of promoting defecation, and improving the slippage of stool during defecation. be able to. This is clear from the reports that pharmaceutical preparations with a mechanism of action that inhibits lipase activity are used as anti-obesity drugs by suppressing the absorption of triglycerides, and are accompanied by an increase in the number of defecations and an increase in oily stools (non-). Patent Document 3).

また、本発明は、脂質分解が抑制され、体外への脂質排出を促進できることから、脂性肌の改善にも好適に用いることができる。 In addition, the present invention can be suitably used for improving oily skin because lipid decomposition is suppressed and lipid excretion to the outside of the body can be promoted.

本発明の組成物は、限定はされないが、医薬品、医薬部外品、化粧品、飲食品、飼料、又は、ペットフードとして調製、加工することが可能である。 The composition of the present invention can be prepared and processed as a pharmaceutical product, a quasi drug, a cosmetic product, a food or drink, a feed, or a pet food, without limitation.

例えば、飲食品として調製する場合、脂質吸収抑制、内臓脂肪蓄積抑制、肥満改善、整腸、腸内細菌業改善、腸内環境改善、便の滑り向上等を機能性として表示した飲食品、すなわち、健康食品、機能性表示食品、病者用食品及び特定保健用食品等として用いることができる。 For example, when prepared as a food or drink, a food or drink that displays as functionality such as suppression of lipid absorption, suppression of visceral fat accumulation, improvement of obesity, intestinal regulation, improvement of intestinal bacterial industry, improvement of intestinal environment, improvement of stool slippage, that is, , Health foods, foods with functional claims, foods for the sick, foods for specified health use, etc.

健康食品、機能性表示食品、病者用食品及び特定保健用食品は、具体的には、固形製剤(錠剤、顆粒剤、細粒剤、散剤、カプセル剤、チュアブル錠など)や液剤(シロップ剤、懸濁剤)、流動食等の各種製剤形態として使用することができる。製剤形態の食品は、公知の医薬製剤と同様に製造することができ、有効成分と、食品として許容できる担体、例えば適当な賦形剤等とを混合した後、慣用の手段を用いて製造することができる。 Specifically, health foods, foods with functional claims, foods for the sick, and foods for specified health use are solid preparations (tablets, granules, fine granules, powders, capsules, chewable tablets, etc.) and liquids (syrups). , Sustainable agent), liquid food and the like. The food product in the form of a preparation can be produced in the same manner as a known pharmaceutical preparation, and is produced by mixing the active ingredient with a carrier acceptable as a food product, for example, a suitable excipient, and the like, and then using conventional means. be able to.

例えば、錠剤であれば、粉末状の活性成分と製薬上許容される担体成分(賦形剤など)とを混合して圧縮成形することにより調製でき、キャンディー(飴)などの製菓錠剤は型に注入する方法で調製してもよい。錠剤は、糖衣コーティングやフィルムコーティングを施してもよい。さらに、錠剤は単層錠であってもよく、二層錠などの積層錠であってもよい。 For example, tablets can be prepared by mixing powdered active ingredients and pharmaceutically acceptable carrier ingredients (excipients, etc.) and compression molding, and confectionery tablets such as candies can be molded into molds. It may be prepared by the method of injection. The tablets may be sugar-coated or film-coated. Further, the tablet may be a single-layer tablet or a laminated tablet such as a two-layer tablet.

顆粒剤などの粉粒剤は、種々の造粒法(押出造粒法、粉砕造粒法、乾式圧密造粒法、流動層造粒法、転動造粒法、高速攪拌造粒法など)により調製してもよく、錠剤は、上記造粒法、打錠法(湿式打錠法、直接打錠法)などを適当に組み合わせて調製できる。 Granules such as granules are available in various granulation methods (extrusion granulation method, pulverized granulation method, dry compaction granulation method, fluidized layer granulation method, rolling granulation method, high-speed stirring granulation method, etc.). The tablets can be prepared by appropriately combining the above-mentioned granulation method, tableting method (wet tableting method, direct tableting method) and the like.

カプセル剤は、慣用の方法により、カプセル(軟質又は硬質カプセル)内に粉粒剤(粉剤、顆粒剤など)又は液剤等を充填することにより調製できる。 Capsules can be prepared by filling capsules (soft or hard capsules) with powders (powder, granules, etc.), liquids, or the like by a conventional method.

液剤は、各成分を担体成分である水性媒体(精製水、エタノール含有精製水など)に溶解又は分散させ、必要により濾過又は滅菌処理し、所定の容器に充填し、滅菌処理することにより調製できる。 The liquid preparation can be prepared by dissolving or dispersing each component in an aqueous medium (purified water, ethanol-containing purified water, etc.) as a carrier component, filtering or sterilizing if necessary, filling in a predetermined container, and sterilizing. ..

軟カプセル剤は表面が滑らかで飲み込みやすく、使用者に好まれる。一般的な軟カプセル剤の製造方法として、平板式、ロータリー方式、シームレス方式が例示される。 Soft capsules have a smooth surface and are easy to swallow, and are preferred by users. Examples of a general method for producing a soft capsule include a flat plate method, a rotary method, and a seamless method.

ロータリー方式(打ち抜き法)の製造は、シート状カプセル皮膜が、流動する充填内容物を挟み込み、回転する円筒型の金型の穴に沿ってカプセル形状に形成する。一方で、シームレス方式(滴下法)の製造は、同心円の多重ノズルからカプセル皮膜組成物と内容物が同時に吐出され、継ぎ目の無いカプセル形状に形成される。 In the production of the rotary method (punching method), a sheet-shaped capsule film sandwiches a flowing filling content and forms a capsule shape along a hole of a rotating cylindrical die. On the other hand, in the seamless method (dropping method), the capsule film composition and the contents are simultaneously discharged from the concentric multiple nozzles to form a seamless capsule shape.

軟カプセル剤の皮膜の基剤は、特に限定はされないが、デンプン、プルラン、セルロース、ポリビニルアルコール、ゼラチン、コハク化ゼラチン等を用いることができ、デンプン、ゼラチン、コハク化ゼラチンが好ましく、ゼラチン、コハク化ゼラチンが更に好ましい。これらは単独で又は二種以上組み合わせて使用してもよい。 The base of the film of the soft capsule is not particularly limited, but starch, pullulan, cellulose, polyvinyl alcohol, gelatin, saccharified gelatin and the like can be used, and starch, gelatin and saccharified gelatin are preferable, and gelatin and succinic are preferable. Gelatinized gelatin is more preferred. These may be used alone or in combination of two or more.

本発明の固形製剤の好ましい剤形は、カプセル剤又は錠剤であり、軟質カプセル(軟カプセル剤、ソフトカプセル)であることがより好ましい。 The preferred dosage form of the solid preparation of the present invention is a capsule or a tablet, and more preferably a soft capsule (soft capsule, soft capsule).

また、スープ類、ジュース類、果汁飲料、牛乳、乳飲料、乳清飲料、乳酸菌飲料、茶飲料、アルコール飲料、コーヒー飲料、炭酸飲料、清涼飲料水、水飲料、ココア飲料、ゼリー状飲料、スポーツ飲料、ダイエット飲料等の液状飲料、プリン、ヨーグルトなどの半固形食品、麺類、菓子類、スプレッド類等として、本発明の組成物を製造することができる。 In addition, soups, juices, fruit juice drinks, milk, milk drinks, milk drinks, lactic acid bacteria drinks, tea drinks, alcoholic drinks, coffee drinks, carbonated drinks, soft drinks, water drinks, cocoa drinks, jelly-like drinks, sports The composition of the present invention can be produced as a beverage, a liquid beverage such as a diet beverage, a semi-solid food such as pudding and yogurt, noodles, confectionery, spreads and the like.

スープ類としては、例えば、味噌汁、クロメ汁、クロメ茶漬け等が挙げられる。限定はされないが、クロメの藻体(藻体の乾燥品であってもよい)を水に浸し、1〜5時間、50〜80℃の条件にて加熱処理することで、クロメ内の有用成分を抽出し、この抽出液を含んだスープ類の具材を製造することが可能となる。また、クロメの藻体の乾燥品、又はその粉砕物を出汁として用い、お吸い物を始め、種々の和食等に利用することも可能である。クロメの藻体の乾燥品、又はその粉砕物を、醤油等へ添加し調味料として利用することも可能である。上記の条件の範囲内にて加熱処理を行うことにより、リパーゼ活性阻害効果に有効な成分を溶出させ、当該成分を効率的に摂取することが期待される。 Examples of soups include miso soup, kurome soup, and kurome chazuke. Although not limited, a useful component in Ecklonia kurome is obtained by immersing the algae of Ecklonia kurome (which may be a dried product of the algae) in water and heat-treating it under the conditions of 50 to 80 ° C. for 1 to 5 hours. It becomes possible to produce ingredients for soups containing this extract. It is also possible to use a dried product of Ecklonia kurome algae or a crushed product thereof as a soup stock, and use it for various Japanese foods such as soup stock. It is also possible to add a dried product of Ecklonia kurome algae or a crushed product thereof to salty sauce or the like and use it as a seasoning. By performing the heat treatment within the range of the above conditions, it is expected that a component effective for the lipase activity inhibitory effect is eluted and the component is efficiently ingested.

また、煮物類として、本発明の組成物を製造することができる。煮物類とは、クロメを原料(材料)の一つとして、水、出汁等と共に煮て、しお、酒、砂糖、みりん等の調味料で味付けを行った料理をいう。煮物類としては、例えば、クロメ佃煮、クロメ煮込み、クロメ含め煮、クロメ煮しめ、クロメ煮付け、煮浸し等が挙げられる。これらの煮物類の中でも、長時間の加熱処理を行うことの観点から、クロメの佃煮、煮込み、含め煮、又は、煮しめが好ましく、クロメの佃煮、又は、煮しめがより好ましい。 In addition, the composition of the present invention can be produced as boiled foods. Boiled foods are dishes that use chrome as one of the raw materials (ingredients), boiled with water, soup stock, etc., and seasoned with seasonings such as shio, sake, sugar, and mirin. Examples of the simmered foods include kurome tsukudani, kurome simmered, simmered with kurome, simmered kurome, simmered kurome, and stewed. Among these simmered foods, from the viewpoint of performing heat treatment for a long time, tsukudani, simmered, simmered or boiled kurome is preferable, and tsukudani or simmered kurome is more preferable.

限定はされないが、クロメの藻体(藻体の乾燥品であってもよい)を水に浸し、出汁や調味料と共に、1〜5時間、50〜80℃などの前述の条件にて加熱処理することで、クロメ内の有用成分を抽出し、この抽出液を含んだ煮物類を製造することが可能となる。上記の条件の範囲内にて加熱処理を行うことにより、リパーゼ活性阻害効果に有効な成分を溶出させ、当該成分を効率的に摂取することが期待される。なお、煮しめや煮込み等において、水気(汁気)が無くなるまで煮詰めることがあるが、上記の条件の範囲内にて加熱処理を行うことで、一旦、リパーゼ活性阻害効果に有効な成分を溶出させ、煮詰める段階や、煮詰め後の温度を下げる段階にて、上記有効成分がクロメや他の具材に染み込むことで、当該成分の効率的な摂取に繋がる。 Although not limited, the algae of Ecklonia kurome (which may be a dried algae) is soaked in water and heat-treated with soup stock and seasonings for 1 to 5 hours under the above-mentioned conditions such as 50 to 80 ° C. By doing so, it becomes possible to extract useful components in kurome and produce simmered foods containing this extract. By performing the heat treatment within the range of the above conditions, it is expected that a component effective for the lipase activity inhibitory effect is eluted and the component is efficiently ingested. In addition, in boiling or boiling, it may be boiled until the water (juice) disappears, but by performing the heat treatment within the above conditions, the components effective for the lipase activity inhibitory effect are once eluted. , At the stage of boiling or lowering the temperature after boiling, the above active ingredient soaks into chrome and other ingredients, leading to efficient intake of the ingredient.

上記のスープ類や煮物類は、惣菜用や中食用の加工品として販売することも可能である。従来のクロメを用いた加工品では、調理時間短縮や生産効率の観点から、強火(90〜100℃等)、短時間(10分以内等)の条件にて調理がされてきた。本発明においては、従来の調理条件では用いられない弱火、長時間の条件にて調理する程、顕著にリパーゼ活性阻害効果、健康機能を高めたカジメ属クロメの加工品を調理することが可能となる。 The above soups and simmered foods can also be sold as processed products for prepared foods and prepared meals. Conventional processed products using chrome have been cooked under high heat (90 to 100 ° C., etc.) and short time (within 10 minutes, etc.) from the viewpoint of shortening cooking time and production efficiency. In the present invention, it is possible to cook a processed product of Ecklonia cava, which has significantly enhanced lipase activity inhibitory effect and health function, as it is cooked under low heat and long-term conditions, which are not used under conventional cooking conditions. Become.

本発明の組成物を飲食品として調製する場合は、種々の食品添加物を配合してもよい。食品添加物としては、例えば、酸化防止剤、色素、香料、調味料、甘味料、酸味料、pH調整剤、品質安定剤、保存剤等が挙げられる。 When the composition of the present invention is prepared as a food or drink, various food additives may be blended. Examples of food additives include antioxidants, pigments, flavors, seasonings, sweeteners, acidulants, pH adjusters, quality stabilizers, preservatives and the like.

本発明の組成物を健康食品、機能性表示食品、病者用食品及び特定保健用食品として調製する場合は、他の脂肪吸収抑制成分を配合してもよい。例えば、難消化性デキストリン、イソマルトデキストリン、EPA、DHA、没食子酸、ターミナリアベリリカ由来没食子酸、セイタカミロバラン果実由来没食子酸、グロビン由来バリン-バリン-チロシン-プロリン、アフリカマンゴノキ由来エラグ酸、イヌリン、ギムネマ酸等が挙げられるがこれに限定されない。 When the composition of the present invention is prepared as a health food, a food with functional claims, a food for the sick, and a food for specified health use, other fat absorption inhibitory components may be blended. For example, indigestible dextrin, isomaltodextrin, EPA, DHA, gallic acid, terminaria berylica-derived gallic acid, seitakamilovalan fruit-derived gallic acid, globin-derived valine-valine-tyrosine-proline, African mangonoki-derived ellagic acid, Examples include, but are not limited to, inulin, gymnemic acid, and the like.

本発明の組成物を医薬品、医薬部外品として調製する場合は、有効成分となり得る、クロメの水抽出物と、好ましくは薬学的に許容される担体を含む製剤として調製することができる。薬学的に許容される担体とは、一般的に、前記有効成分とは反応しない、不活性の、無毒の、固体若しくは液体の、増量剤、希釈剤又はカプセル化材料等をいい、例えば、水、エタノール、ポリオール類、適切なそれらの混合物、植物性油等の溶媒又は分散媒体等が挙げられる。 When the composition of the present invention is prepared as a pharmaceutical product or a quasi-drug, it can be prepared as a preparation containing an aqueous extract of Ecklonia kurome, which can be an active ingredient, and preferably a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier generally refers to an inert, non-toxic, solid or liquid bulking agent, diluent, encapsulating material, etc. that does not react with the active ingredient, such as water. , Ethanol, polyols, suitable mixtures thereof, solvents such as vegetable oils or dispersion media and the like.

医薬品、医薬部外品は、経口により、非経口により、例えば、口腔内に、消化管内に、又は鼻腔内に投与される。経口投与製剤としては、固形製剤(錠剤、顆粒剤、細粒剤、散剤、カプセル剤、チュアブル錠など)や、液剤(シロップ剤、懸濁剤、吸入剤)等が挙げられる。非経口投与製剤としては、点滴剤、点鼻剤及び注射剤等が挙げられる。 Pharmaceuticals and quasi-drugs are administered orally, parenterally, for example, in the oral cavity, in the digestive tract, or in the nasal cavity. Examples of the orally administered preparation include solid preparations (tablets, granules, fine granules, powders, capsules, chewable tablets, etc.) and liquid preparations (syrups, suspensions, inhalants) and the like. Examples of the parenteral administration preparation include infusions, nasal drops, injections and the like.

医薬品、医薬部外品は、さらに医薬分野において慣用されている添加剤を含んでいてもよい。そのような添加剤には、例えば、賦形剤、結合剤、崩壊剤、滑沢剤、抗酸化剤、着色剤、矯味剤等があり、必要に応じて適宜使用できる。長時間作用できるように徐放化するため、既知の遅延剤等でコーティングすることもできる。医薬品、医薬部外品は、さらに必要に応じてその他の添加剤や薬剤、例えば制酸剤、胃粘膜保護剤を加えてもよい。 Pharmaceuticals and quasi-drugs may further contain additives commonly used in the pharmaceutical field. Such additives include, for example, excipients, binders, disintegrants, lubricants, antioxidants, colorants, flavoring agents and the like, which can be used as appropriate as needed. Since it is sustained-release so that it can act for a long time, it can be coated with a known retarder or the like. For pharmaceutical products and quasi-drugs, other additives and drugs such as antacids and gastric mucosa protective agents may be added as needed.

医薬品、医薬部外品は、口腔用組成物、内服組成物などの形態で適用することができる。また医薬品、医薬部外品を治療的に使用してもよいし、非治療的に使用してもよい。 Pharmaceuticals and quasi-drugs can be applied in the form of oral compositions, oral compositions and the like. In addition, pharmaceuticals and quasi-drugs may be used therapeutically or non-therapeutically.

また、医薬品、医薬部外品、化粧品等の形態で用いる場合、皮膚における微生物が産生するリパーゼ等により皮脂類から脂肪酸が生成し、生じた脂肪酸が好中球を活性化し、活性化された好中球が活性酸素を放出して、肌荒れの一因となり得る。クロメの水抽出物を外用剤等の剤形で配合することにより、ニキビ等の肌荒れに対して効果的なリパーゼ活性阻害用組成物を提供し得る。 In addition, when used in the form of pharmaceuticals, quasi-drugs, cosmetics, etc., fatty acids are produced from sebum by lipases produced by microorganisms in the skin, and the generated fatty acids activate neutrophils and are activated. Neutrophils release active oxygen, which can contribute to rough skin. By blending the water extract of Ecklonia kurome in the form of an external preparation or the like, it is possible to provide a composition for inhibiting lipase activity that is effective against rough skin such as acne.

クロメの水抽出物の成人1日あたりの経口による摂取量又は投与量は、個体の状態、体重、性別、年齢、素材の活性、摂取又は投与経路、摂取又は投与スケジュール、製剤形態又はその他の要因により適宜決定することができる。クロメの水抽出物の成人1日あたりの経口による摂取量又は投与量は、例えば、乾燥固形分換算にて、500mg/日以上が好ましく、800mg/日以上がより好ましく、1000mg/日以上が更に好ましく、1500mg/日以上が特に好ましく、2000mg/日以上が最も好ましい。 The daily oral intake or dose of Ecklonia kurome's water extract for adults is the individual's condition, body weight, gender, age, material activity, intake or route of administration, intake or administration schedule, formulation form or other factors. Can be appropriately determined. The oral intake or dose of the water extract of Ecklonia kurome per adult per day is, for example, preferably 500 mg / day or more, more preferably 800 mg / day or more, and further 1000 mg / day or more in terms of dry solid content. Preferably, 1500 mg / day or more is particularly preferable, and 2000 mg / day or more is most preferable.

クロメの水抽出物の成人1日あたりの経口による摂取量又は投与量は、例えば、45g/日以下が好ましく、40g/日以下がより好ましく、35g/日以下が更に好ましく、30g/日以下が特に好ましく、25g/日以下が最も好ましい。 The oral intake or dose of the water extract of Ecklonia kurome per adult per day is, for example, preferably 45 g / day or less, more preferably 40 g / day or less, further preferably 35 g / day or less, and 30 g / day or less. It is particularly preferable, and 25 g / day or less is most preferable.

クロメの水抽出物の成人1日あたりの経口による摂取量又は投与量は、例えば、500mg〜45g/日が好ましく、800mg〜40g/日がより好ましく、1000mg〜35g/日が更に好ましく、1500mg〜30g/日が特に好ましく、2000mg〜25g/日が最も好ましい。 The oral intake or dose of the water extract of Ecklonia kurome per adult per day is, for example, preferably 500 mg to 45 g / day, more preferably 800 mg to 40 g / day, further preferably 1000 mg to 35 g / day, and 1500 mg to 1500 mg. 30 g / day is particularly preferable, and 2000 mg to 25 g / day is most preferable.

クロメの水抽出物の含有量は、上記の摂取量又は投与量となる量とすることができる。なお、成人1日あたりの経口による摂取量又は投与量は、剤形に合わせて、例えばカプセル剤であれば、1〜6カプセル、1〜4カプセル、1〜3カプセル、又は1〜2カプセルに分けて服用してもよい。 The content of the water extract of Ecklonia kurome can be an amount that is the above-mentioned intake amount or dose. The oral intake or dose per day for adults should be adjusted to 1 to 6 capsules, 1 to 4 capsules, 1 to 3 capsules, or 1 to 2 capsules, for example, in the case of capsules, according to the dosage form. You may take it separately.

本発明の組成物は、1日1回〜数回に分け、通常、1日1〜6回、1日1〜3回、1日1〜2回又は任意の期間及び間隔で摂取若しくは投与され得る。 The composition of the present invention is divided into 1 to several times a day, and is usually ingested or administered 1 to 6 times a day, 1 to 3 times a day, 1 to 2 times a day, or at arbitrary periods and intervals. obtain.

[カジメ属クロメの水抽出物又は加工品の製造方法]
本発明において、カジメ属クロメの水抽出物又は加工品の製造方法は、(1)カジメ属クロメを、50〜80℃の熱水により、1〜5時間抽出する工程を含む。
[Manufacturing method of water extract or processed product of Ecklonia cava]
In the present invention, the method for producing an aqueous extract or processed product of Ecklonia cava includes (1) a step of extracting Ecklonia cava with hot water at 50 to 80 ° C. for 1 to 5 hours.

上記工程としては、リパーゼ活性阻害用組成物に記載の温度条件、時間条件等の記載に準じて、適宜設定することが可能である。 The above steps can be appropriately set according to the description of the temperature conditions, time conditions, etc. described in the composition for inhibiting lipase activity.

次に、実施例により本発明を具体的に説明するが、本発明は以下の実施例に限定されるものではない。また、実施例において示すエキスの量は、特に明示がない限り、乾燥固形分換算量である。 Next, the present invention will be specifically described with reference to Examples, but the present invention is not limited to the following Examples. Further, the amount of the extract shown in the examples is a dry solid content equivalent amount unless otherwise specified.

[試験例1:クロメの水抽出物の抽出条件の検討]
カジメ属クロメ(学名:Ecklonia kurome)の藻体(鳥取県産、収穫時期:4月、部位:葉体及び茎、生育年数:2〜5年)から5gずつの小片を作成し、様々な温度と、1時間又は3時間の抽出時間とを組み合わせて被験試料としての水抽出物を調製し、抽出物量及び粘性を指標とした抽出条件を検討した。抽出物量に関する結果を表1に示す。
[Test Example 1: Examination of extraction conditions for water extract of Ecklonia kurome]
Small pieces of 5 g each are prepared from the algae of Ecklonia kurome (scientific name: Ecklonia kurome) (produced in Tottori prefecture, harvest time: April, site: leaf body and stem, growing years: 2 to 5 years), and various temperatures. And an extraction time of 1 hour or 3 hours were combined to prepare an aqueous extract as a test sample, and the extraction conditions using the amount and viscosity of the extract as an index were examined. Table 1 shows the results regarding the amount of extract.

Figure 2021155419
Figure 2021155419

表1に示す通り、クロメの水抽出物において、温度依存的、抽出時間依存的な結果が得られ、高温になるにつれて抽出物の量は増加し、また、各抽出温度でも抽出時間が長い方が得られる抽出物の量は多くなることが確認された。 As shown in Table 1, in the water extract of Kurome, temperature-dependent and extraction time-dependent results were obtained, the amount of the extract increased as the temperature increased, and the extraction time was longer at each extraction temperature. It was confirmed that the amount of extract obtained was large.

また、粘性に関する結果を表2に示す。粘性の評価は、30mLの各被験試料をフィルターろ過(メッシュサイズ:3μm、ADVANTEC社製)した場合に、ろ過完了まで15分以上時間が必要であり、目詰まりするたびにフィルターを交換して3枚以上使用したものを「粘性あり:×」と評価した。 The results regarding viscosity are shown in Table 2. For the evaluation of viscosity, when 30 mL of each test sample was filtered by a filter (mesh size: 3 μm, manufactured by ADVANTEC), it took 15 minutes or more to complete the filtration, and the filter was replaced every time the sample was clogged. Those using more than one sheet were evaluated as "viscous: x".

Figure 2021155419
Figure 2021155419

表2に示す通り、50℃(1時間処理、及び、3時間処理)、60℃(1時間処理、及び、3時間処理)、70℃(1時間処理)のクロメの水抽出物には粘性があり、フィルター濾過による操作には時間を要した。他方、70℃、3時間の条件より高温側条件でのクロメの水抽出物では、フィルター濾過時の明らかな粘性が認められず、比較的簡便に調製することができた。抽出物の調製や原料としての利便性の観点から、70℃(3時間処理)より高温側の条件が望ましいことが確認された。 As shown in Table 2, the water extract of Ecklonia kurome at 50 ° C. (1 hour treatment and 3 hour treatment), 60 ° C. (1 hour treatment and 3 hour treatment), and 70 ° C. (1 hour treatment) is viscous. Therefore, it took time to operate by filtering. On the other hand, in the water extract of Ecklonia kurome under the condition of 70 ° C. for 3 hours, which was higher than the condition of 3 hours, no obvious viscosity was observed at the time of filter filtration, and the preparation was relatively easy. From the viewpoint of preparation of the extract and convenience as a raw material, it was confirmed that the condition on the higher temperature side than 70 ° C. (3 hour treatment) is desirable.

[試験例2:抽出条件によるリパーゼ活性阻害効果の検討]
各抽出温度・抽出時間から得られたクロメの水抽出物(被験試料)を用いて、リパーゼ活性阻害試験を行った。リパーゼ活性阻害試験には、4−メチルウンベリフェロンのオレイン酸エステル(4−MUO)を基質として用いた。0.05mlの4−MUO溶液(10−4mM)に、0.1mlの被験試料を加え混合した後に、3U/mLの膵リパーゼ溶液0.05mlを添加し、20分間、37度で反応させた後に、0.1mlの塩酸を加え、反応を停止させた。反応溶液とクエン酸溶液を混合させた溶液における、反応によって生じた4−メチルウンベリフェロンの蛍光(励起波長320nm、蛍光波長450nm)を蛍光マイクロプレートリーダーにて測定した。活性値は被験試料無添加の値を100%として各被験試料の活性値(IC50)を算出した。活性値が低いほどリパーゼ阻害作用が強いことを示している。結果を図1に示す。図1中、破線は1時間の抽出時間での結果を示し、実線は3時間の抽出時間での結果を示している。
[Test Example 2: Examination of lipase activity inhibitory effect by extraction conditions]
A lipase activity inhibition test was conducted using an aqueous extract of Ecklonia kurome (test sample) obtained from each extraction temperature and extraction time. In the lipase activity inhibition test, oleic acid ester (4-MUO) of 4-methylumbelliferone was used as a substrate. To 0.05 ml of 4-MUO solution ( 10-4 mM), 0.1 ml of the test sample was added and mixed, then 0.05 ml of 3 U / mL pancreatic lipase solution was added, and the mixture was reacted at 37 ° C. for 20 minutes. After that, 0.1 ml of hydrochloric acid was added to stop the reaction. The fluorescence of 4-methylumbelliferone (excitation wavelength 320 nm, fluorescence wavelength 450 nm) generated by the reaction in a mixed solution of the reaction solution and the citrate solution was measured with a fluorescence microplate reader. As the activity value, the activity value (IC50) of each test sample was calculated with the value without addition of the test sample as 100%. The lower the activity value, the stronger the lipase inhibitory effect. The results are shown in FIG. In FIG. 1, the broken line shows the result at the extraction time of 1 hour, and the solid line shows the result at the extraction time of 3 hours.

図1に示す通り、70℃、3時間で調製したクロメの水抽出物が最も顕著なリパーゼ活性阻害を示した。また興味深いことに、70℃から低温側、高温側に温度条件をシフトさせるにつれて、リパーゼ活性阻害の程度が弱くなることがわかった。 As shown in FIG. 1, the water extract of Ecklonia kurome prepared at 70 ° C. for 3 hours showed the most remarkable inhibition of lipase activity. Interestingly, it was found that the degree of lipase activity inhibition decreased as the temperature conditions were shifted from 70 ° C. to the low temperature side and the high temperature side.

低温側の粘性溶液と高温側の溶液では溶液中に存在する成分は異なることが予想されるが、結果として似た結果が得られた。このことから、70℃における抽出条件は各クロメ成分の割合がバランスよく抽出されていることが示唆された。調製方法の簡便さとリパーゼ活性阻害評価の結果から、70℃、3時間抽出が最適であると判断した。また、50℃〜80℃、1〜3時間抽出においても、他の抽出温度と比較して高い阻害効果が見られたことから、クロメの水抽出物の大量調製を行う際の抽出条件は、この範囲内で管理することが適切であることが確認された。 It is expected that the components present in the solution are different between the viscous solution on the low temperature side and the solution on the high temperature side, but similar results were obtained as a result. From this, it was suggested that the ratio of each chrome component was extracted in a well-balanced manner under the extraction conditions at 70 ° C. From the simplicity of the preparation method and the results of the evaluation of lipase activity inhibition, it was judged that extraction at 70 ° C. for 3 hours was optimal. In addition, even in the extraction at 50 ° C. to 80 ° C. for 1 to 3 hours, a high inhibitory effect was observed as compared with other extraction temperatures. It was confirmed that it is appropriate to manage within this range.

[試験例3:オルリスタットとのリパーゼ活性阻害効果の比較による、クロメの水抽出物の1日投与量の検討]
オルリスタットと、クロメの水抽出物とを用い、試験例2と同様の方法によりリパーゼ活性阻害試験を行った。オルリスタットは、オルリスタットは、リパーゼ阻害により脂質吸収抑制作用を有することが知られている成分である。
[Test Example 3: Examination of daily dose of water extract of Ecklonia kurome by comparison of lipase activity inhibitory effect with orlistat]
A lipase activity inhibition test was carried out by the same method as in Test Example 2 using orlistat and a water extract of Ecklonia kurome. Orlistat is a component known to have a lipid absorption inhibitory effect by inhibiting lipase.

クロメの水抽出物としては、70℃、3時間で調製したクロメの水抽出物を用いた。リパーゼ活性阻害試験(IC50)の両成分における比較結果を表3に示す。 As the water extract of Ecklonia kurome, the water extract of Ecklonia kurome prepared at 70 ° C. for 3 hours was used. Table 3 shows the comparison results of both components of the lipase activity inhibition test (IC50).

Figure 2021155419
Figure 2021155419

表3に示す通り、IC50値を比較すると、オルリスタットがクロメの水抽出物の268.3倍であった。 As shown in Table 3, when the IC50 values were compared, the orlistat was 268.3 times that of the water extract of Ecklonia kurome.

オルリスタットとの有効量については、「J.Zhiら、Retrospective population-based analysis of the dose-response (fecal fat excretion) relationship of orlistat in normal and obese volunteers Clin Pharmacol Ther. 1994 Jul;56(1):82-5.」のTable IIにおいて、ED50の95%信頼区間が、30.2〜166.0(mg/day)であることが示されている。 For the effective amount with orlistat, see "J. Zhi et al., Retrospective population-based analysis of the dose-response (fecal fat excretion) relationship of orlistat in normal and obese volunteers Clin Pharmacol Ther. 1994 Jul; 56 (1): 82 In Table II of "-5.", it is shown that the 95% confidence interval of ED50 is 30.2 to 166.0 (mg / day).

上記論文に記載のオルリスタットの有効量と、表3の結果とに基づき、クロメの水抽出物の有効量(ED50)を換算すると、表4に記載の通り、8g/day〜45g/dayであることが確認された。この数値範囲は、医薬品であるオルリスタットと同程度の効果を期待する場合であるので、食品として用いる場合には、1日摂取量は、500mg以上であれば適切な健康効果が期待される。 Based on the effective amount of orlistat described in the above paper and the results in Table 3, the effective amount (ED50) of the water extract of Ecklonia kurome is converted to 8 g / day to 45 g / day as shown in Table 4. It was confirmed that. Since this numerical range is expected to have the same effect as orlistat, which is a pharmaceutical product, when used as a food, an appropriate health effect is expected if the daily intake is 500 mg or more.

Figure 2021155419
Figure 2021155419

[試験例4 採取時期によるリパーゼ活性の検討]
鳥取県の海岸域で2020年の4月末に採取したクロメの藻体を水で軽く洗い、37℃の条件で乾燥機(メーカー:ETTAS(アズワン) 型番:OFW−450B)にて1日乾燥した。乾燥後、0.5g秤量し、フードプロセッサーで細かく粉砕した。粉砕後のクロメに35mL蒸留水を加え、恒温槽で70℃、3時間静置して抽出を行った。抽出後、ガラスフィルターを用いて水流アスピレーターで吸引ろ過を行い、抽出液から海藻残渣を除去した。その後、抽出液は3μm、0.45μmフィルターを用い、吸引ろ過した。フィルターろ過した抽出液を液体窒素で凍らせた後、3日間凍結乾燥した。その後、試験例2と同様の方法で、各被験試料の活性値(IC50)を算出した。
[Test Example 4 Examination of lipase activity depending on the collection time]
The algae of Ecklonia kurome collected at the end of April 2020 in the coastal area of Tottori Prefecture were lightly washed with water and dried in a dryer (manufacturer: ETTAS (As One) model number: OFW-450B) for one day at 37 ° C. .. After drying, 0.5 g was weighed and finely ground with a food processor. 35 mL of distilled water was added to the pulverized chrome, and the mixture was allowed to stand at 70 ° C. for 3 hours in a constant temperature bath for extraction. After extraction, suction filtration was performed with a water flow aspirator using a glass filter to remove seaweed residue from the extract. Then, the extract was suction-filtered using a 3 μm and 0.45 μm filter. The filtered extract was frozen in liquid nitrogen and then lyophilized for 3 days. Then, the activity value (IC50) of each test sample was calculated by the same method as in Test Example 2.

Figure 2021155419
Figure 2021155419

表5に示す通り、4月末に採取されたクロメを原料に用いた場合、顕著なリパーゼ活性阻害効果が示された。なお、結果は示していないが、3月までに採取されたクロメを原料に用いた場合もリパーゼ活性阻害効果が確認されたが、4月末に採取されたクロメを原料に用いた場合は、より高い効果であることが認められた。 As shown in Table 5, when the chrome collected at the end of April was used as a raw material, a remarkable lipase activity inhibitory effect was shown. Although the results are not shown, the lipase activity inhibitory effect was confirmed even when the chrome collected by March was used as the raw material, but when the chrome collected at the end of April was used as the raw material, it was more effective. It was found to be highly effective.

[試験例5 生育期間によるリパーゼ活性の検討]
鳥取県の海岸域で採取したクロメのうち、生育期間が1年〜2年程度であるものの藻体を、水で軽く洗い、その後水気を切り、フードプロセッサーで細かく粉砕した。粉砕後のクロメ5gに35mL蒸留水を加え、恒温槽で70℃、3時間静置して抽出を行った。抽出後、ガラスフィルターを用いて水流アスピレーターで吸引ろ過を行い、抽出液から海藻残渣を除去した。その後、抽出液は3μm、0.45μmフィルターを用い、吸引ろ過した。ろ過後の抽出液を液体窒素で凍らせた後、3日間凍結乾燥した。その後、試験例2と同様の方法で、各被験試料の活性値(IC50)を算出した。
[Test Example 5 Examination of lipase activity according to growth period]
Of the Ecklonia kurome collected in the coastal area of Tottori Prefecture, the algae, which have a growing period of about 1 to 2 years, were lightly washed with water, drained, and finely crushed with a food processor. 35 mL of distilled water was added to 5 g of the pulverized chrome, and the mixture was allowed to stand at 70 ° C. for 3 hours in a constant temperature bath for extraction. After extraction, suction filtration was performed with a water flow aspirator using a glass filter to remove seaweed residue from the extract. Then, the extract was suction-filtered using a 3 μm and 0.45 μm filter. The extracted extract after filtration was frozen in liquid nitrogen and then freeze-dried for 3 days. Then, the activity value (IC50) of each test sample was calculated by the same method as in Test Example 2.

Figure 2021155419
Figure 2021155419

表6に示す通り、生育期間が1年〜2年程度であるクロメを原料に用いた場合、より高いリパーゼ活性阻害効果が示された。 As shown in Table 6, when chrome having a growth period of about 1 to 2 years was used as a raw material, a higher lipase activity inhibitory effect was shown.

[試験例6 採取後の乾燥によるリパーゼ活性の検討]
鳥取県の海岸域で採取したクロメを、水で軽く洗い、その後、屋外にて天日干しを行い、1日乾燥させた。乾燥後、クロメの乾燥物を0.5g秤量し、フードプロセッサーで細かく粉砕した。粉砕後のクロメに蒸留水を35mL加え、恒温槽で70℃、3時間静置して抽出を行った。水抽出後、ガラスフィルターを用いて水流アスピレーターで吸引ろ過を行い、抽出液から海藻残渣を除去した。その後、抽出液は3μm、0.45μmフィルターを用い、吸引ろ過を行った。ろ過後の抽出液を液体窒素で凍らせた後、3日間凍結乾燥した。その後、試験例2と同様の方法で、各被験試料の活性値(IC50)を算出した。
[Test Example 6 Examination of lipase activity by drying after collection]
The kurome collected in the coastal area of Tottori prefecture was lightly washed with water, then dried outdoors in the sun and dried for one day. After drying, 0.5 g of dried Ecklonia kurome was weighed and finely ground with a food processor. 35 mL of distilled water was added to the pulverized chrome, and the mixture was allowed to stand at 70 ° C. for 3 hours in a constant temperature bath for extraction. After water extraction, suction filtration was performed with a water flow aspirator using a glass filter to remove seaweed residue from the extract. Then, the extract was suction-filtered using a 3 μm and 0.45 μm filter. The extracted extract after filtration was frozen in liquid nitrogen and then freeze-dried for 3 days. Then, the activity value (IC50) of each test sample was calculated by the same method as in Test Example 2.

Figure 2021155419
Figure 2021155419

表7に示す通り、抽出工程を行う前にクロメを乾燥させ、クロメの乾燥物を原料に用いた場合、より高いリパーゼ活性阻害効果が示された。 As shown in Table 7, when the kurome was dried before the extraction step and the dried kurome was used as a raw material, a higher lipase activity inhibitory effect was shown.

[試験例7 エタノール抽出物とのリパーゼ活性の比較検討]
水抽出物の調製としては、鳥取県の海岸域で採取したクロメの藻体を水で軽く洗い、37℃の条件で乾燥機乾燥機(メーカー:ETTAS(アズワン) 型番:OFW−450B)にて1日乾燥した。乾燥後、クロメの乾燥物を0.5g秤量し、フードプロセッサーで粉砕した。粉砕後のクロメに蒸留水を35mL加え、恒温槽で70℃、3時間静置して抽出を行った。抽出後、ガラスフィルターを用いて水流アスピレーターで吸引ろ過を行い、抽出液から海藻残渣を除去した。その後、3μm、0.45μmフィルターの順に抽出液をろ過した。フィルターろ過した抽出液を液体窒素で凍らせた後、3日間凍結乾燥することによって凍結乾燥粉末を調製した。その後、試験例2と同様の方法で、被験試料の活性値(IC50)を算出した。
[Test Example 7 Comparison of lipase activity with ethanol extract]
To prepare the water extract, lightly wash the algae of Kurome collected in the coastal area of Tottori prefecture with water, and use a dryer (manufacturer: ETTAS (As One) model number: OFW-450B) at 37 ° C. It was dried for one day. After drying, 0.5 g of dried Ecklonia kurome was weighed and pulverized with a food processor. 35 mL of distilled water was added to the pulverized chrome, and the mixture was allowed to stand at 70 ° C. for 3 hours in a constant temperature bath for extraction. After extraction, suction filtration was performed with a water flow aspirator using a glass filter to remove seaweed residue from the extract. Then, the extract was filtered in the order of 3 μm and 0.45 μm filters. A lyophilized powder was prepared by freezing the filtered extract with liquid nitrogen and then lyophilizing for 3 days. Then, the activity value (IC50) of the test sample was calculated by the same method as in Test Example 2.

エタノール抽出物の調製としては、鳥取県の海岸域で採取したクロメの藻体を水で軽く洗って水分をとり、約5g秤量した。その後、−30℃にて凍結し、凍結乾燥機(メーカー:EYELA 型番:FDU−2110、他の凍結乾燥処理でも同様)を用いて3日間乾燥した。乾燥後、クロメの乾燥物を0.5g秤量し、フードプロセッサーで粉砕した。粉砕後のクロメにエタノールを35mL加え、恒温槽で70℃、3時間静置して抽出を行った。なお、エタノール抽出後に凍結乾燥処理によって得られる被験試料は水抽出の条件より少ないため、(0.5g/35mL)×4セット調製した。抽出後、ガラスフィルターを用いて水流アスピレーターで吸引ろ過を行い、抽出液から海藻残渣を取り除いた。このとき、4セット分を全て合わせて抽出液全量は120mLとなった。その後、抽出液はロータリーエバポレーターを用いて濃縮・有機溶媒除去を行った。6倍濃縮されたところで(120mL→20mL)、計50−60mLの蒸留水を数回に分けて加え、エタノール臭が認められなくなるまで濃縮・有機溶媒除去を行った。最後に抽出液を、液体窒素で凍らせた後、3日間凍結乾燥し、37.8mgの凍結乾燥粉末を得た。その後、試験例2と同様の方法で、被験試料の活性値(IC50)を算出した。
なお、エタノールによる抽出収率が水よりもかなり低いため、水又はエタノールによる抽出前の乾燥させたクロメの重量を基準としてIC50を算出した。
To prepare the ethanol extract, the algae of Ecklonia kurome collected in the coastal area of Tottori Prefecture were lightly washed with water to remove water, and about 5 g was weighed. Then, it was frozen at −30 ° C. and dried for 3 days using a freeze-dryer (manufacturer: EYELA model number: FDU-2110, the same applies to other freeze-drying treatments). After drying, 0.5 g of dried Ecklonia kurome was weighed and pulverized with a food processor. 35 mL of ethanol was added to the crushed chrome, and the mixture was allowed to stand at 70 ° C. for 3 hours in a constant temperature bath for extraction. Since the number of test samples obtained by freeze-drying after ethanol extraction was less than the conditions for water extraction, (0.5 g / 35 mL) x 4 sets were prepared. After extraction, suction filtration was performed with a water flow aspirator using a glass filter to remove seaweed residue from the extract. At this time, the total volume of the extract was 120 mL in total for all four sets. Then, the extract was concentrated and the organic solvent was removed using a rotary evaporator. When it was concentrated 6 times (120 mL → 20 mL), a total of 50-60 mL of distilled water was added in several portions, and concentration and removal of the organic solvent were carried out until no ethanol odor was observed. Finally, the extract was frozen in liquid nitrogen and then lyophilized for 3 days to obtain 37.8 mg lyophilized powder. Then, the activity value (IC50) of the test sample was calculated by the same method as in Test Example 2.
Since the extraction yield with ethanol is considerably lower than that with water, the IC50 was calculated based on the weight of dried kurome before extraction with water or ethanol.

Figure 2021155419
Figure 2021155419

表8に示す通り、クロメを原料とする場合、抽出収率及びリパーゼ活性阻害効果の観点から、水抽出物が好ましいことが認められた。 As shown in Table 8, when chrome was used as a raw material, it was confirmed that the water extract was preferable from the viewpoint of the extraction yield and the lipase activity inhibitory effect.

Claims (12)

カジメ属クロメ(学名:Ecklonia kurome)の水抽出物を有効量含有する、リパーゼ活性阻害用組成物。 A composition for inhibiting lipase activity, which contains an effective amount of a water extract of Ecklonia kurome (scientific name: Ecklonia kurome). カジメ属クロメ(学名:Ecklonia kurome)の水抽出物を有効量含有する、脂質吸収抑制用、便の滑り向上用、又は整腸用組成物。 A composition for suppressing lipid absorption, improving stool slippage, or intestinal regulation, which contains an effective amount of a water extract of Ecklonia kurome (scientific name: Ecklonia kurome). 前記カジメ属クロメが、クロメの乾燥物である、請求項1又は2に記載の組成物。 The composition according to claim 1 or 2, wherein the Ecklonia cava genus Ecklonia cava is a dried product of Ecklonia cava. 前記カジメ属クロメの抽出部位が、葉体、及び/又は、茎である、請求項1〜3のいずれか1項に記載の組成物。 The composition according to any one of claims 1 to 3, wherein the extraction site of Ecklonia cava is a frond and / or a stem. 前記カジメ属クロメの生育期間が、1年〜6年である、請求項1〜4のいずれか1項に記載の組成物。 The composition according to any one of claims 1 to 4, wherein the growing period of Ecklonia cava is 1 to 6 years. 前記抽出物を得るための抽出温度が、50〜80℃である、請求項1〜5のいずれか1項に記載の組成物。 The composition according to any one of claims 1 to 5, wherein the extraction temperature for obtaining the extract is 50 to 80 ° C. 前記抽出物を得るための抽出時間が、1〜5時間である、請求項1〜6のいずれか1項に記載の組成物。 The composition according to any one of claims 1 to 6, wherein the extraction time for obtaining the extract is 1 to 5 hours. 医薬品、医薬部外品、化粧品、又は、飲食品である、請求項1〜7のいずれか1項に記載の組成物。 The composition according to any one of claims 1 to 7, which is a pharmaceutical product, a quasi drug, a cosmetic product, or a food or drink. 1日摂取量が、乾燥固形分換算にて、500mg以上である、請求項1〜8のいずれか1項に記載の組成物。 The composition according to any one of claims 1 to 8, wherein the daily intake is 500 mg or more in terms of dry solid content. 以下の工程:
(1)カジメ属クロメを、50〜80℃の熱水により、1〜5時間抽出する工程を含む、カジメ属クロメの水抽出物又は加工品の製造方法。
The following steps:
(1) A method for producing an aqueous extract or processed product of Ecklonia cava, which comprises a step of extracting Ecklonia cava with hot water at 50 to 80 ° C. for 1 to 5 hours.
脂質吸収抑制作用が高められてなるカジメ属クロメの水抽出物又は加工品である、請求項10に記載の方法。 The method according to claim 10, which is a water extract or processed product of Ecklonia cava, which has an enhanced lipid absorption inhibitory effect. カジメ属クロメ(学名:Ecklonia kurome)の水抽出物を有効量含有し、
該抽出物における加熱温度が、50〜80℃であり、
該抽出物における抽出時間が、1〜5時間である、
カジメ属クロメの加工品。
Contains an effective amount of a water extract of Ecklonia kurome (scientific name: Ecklonia kurome),
The heating temperature in the extract is 50-80 ° C.
The extraction time in the extract is 1-5 hours.
Processed product of Ecklonia cava.
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