JP2020178581A - Fat active metabolism improving composition - Google Patents
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- 108010024636 Glutathione Proteins 0.000 claims abstract description 26
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Abstract
Description
本発明は、グルタチオン及びカルニチンを有効成分として含むに脂質代謝改善剤及び改善方法に関する。 The present invention relates to a lipid metabolism improving agent and an improving method containing glutathione and carnitine as active ingredients.
近年、世界的に肥満化傾向が顕著になってきており、体脂肪の蓄積という肥満だけでなく、高脂血症、高血圧、糖尿病など生活習慣病の増加が問題となっている。 In recent years, the tendency toward obesity has become remarkable worldwide, and not only obesity such as accumulation of body fat but also increase in lifestyle-related diseases such as hyperlipidemia, hypertension and diabetes has become a problem.
体脂肪の減少には、運動、特に有酸素運動が体脂肪の減少に有効とされているが、移動手段の発達、生活環境の改善などで歩行などの軽度な運動が減少し、有酸素運動により、体脂肪を減少させることが難しくなっている。 Exercise, especially aerobic exercise, is said to be effective in reducing body fat, but mild exercise such as walking decreases due to the development of transportation means and improvement of living environment, and aerobic exercise This makes it difficult to reduce body fat.
L−カルニチンは、細胞内のミトコンドリア内膜に存在するアミノ酸の一つで、脂肪酸をミトコンドリア内に取り込み脂肪酸をエネルギーとして使用する際に使用され、脂質代謝に関与していることが知られているため、体脂肪減少効果があるとされているが、その効果は充分ではないと記載されている(特許文献1)。そこで、カルニチンと他の成分との組み合わせが検討されている。例えば、特許文献2では、大豆レシチンなどの主成分として含まれるホスファチジルコリンを、脱アシル化することにより得られるグリセロホスホコリンと組み合わせ、特許文献3では、ハス胚芽の抽出物との組み合わせを開示している。 L-carnitine is one of the amino acids present in the inner mitochondrial membrane of cells, and is used when fatty acids are taken into mitochondria and used as energy, and is known to be involved in lipid metabolism. Therefore, it is said that it has a body fat reducing effect, but it is described that the effect is not sufficient (Patent Document 1). Therefore, a combination of carnitine and other components is being studied. For example, Patent Document 2 discloses a combination of phosphatidylcholine contained as a main component of soybean lecithin and the like with glycerophosphocholine obtained by deacylation, and Patent Document 3 discloses a combination with an extract of sacred germ. There is.
そこで、本発明では、体脂肪減少や肥満防止などの効果を有する組成物を得ることを課題として、鋭意検討を行った。その結果、カルニチン及びグルタチオンを配合した組成物は、脂肪細胞への分化を抑制することを見出し本発明を完成させた。 Therefore, in the present invention, an earnest study has been carried out with the object of obtaining a composition having effects such as reduction of body fat and prevention of obesity. As a result, it was found that the composition containing carnitine and glutathione suppresses the differentiation into adipocytes, and completed the present invention.
本発明は、カルニチン及びグルタチオンを含有することを特徴とする脂肪細胞への分化抑制し、脂質蓄積抑制する組成物、または脂質代謝を活性化する組成物である。
(1)カルニチン及びグルタチオンを含有する脂質蓄積抑制用組成物
(2)カルニチン及びグルタチオンを含有する脂質代謝活性用組成物
(3)前記(1)または(2)の組成物を含む食品
(4)前記(1)または(2)の組成物を含む医薬品
The present invention is a composition that suppresses differentiation into adipocytes and suppresses lipid accumulation, or a composition that activates lipid metabolism, which is characterized by containing carnitine and glutathione.
(1) A composition for suppressing lipid accumulation containing carnitine and glutathione (2) A composition for activating lipid metabolism containing carnitine and glutathione (3) A food containing the composition of (1) or (2) above (4) A pharmaceutical product containing the composition of (1) or (2).
本発明は、脂肪細胞への分化を抑制するため、体内脂肪の蓄積を抑制する効果などを有する食品等に利用することができる。グルタチオンは、酵母等に含まれているため、酵母や酵母エキス含有のグルタチオンとカルニチンとを組み合わせると酵母や酵母エキスが持つ栄養成分も同時に摂取でき、代謝改善機能を有する調味料などの食品として使用することもできる。 Since the present invention suppresses differentiation into adipocytes, it can be used for foods and the like having an effect of suppressing the accumulation of fat in the body. Since glutathion is contained in yeast, etc., when glutathion containing yeast or yeast extract is combined with carnitine, the nutritional components of yeast or yeast extract can be taken at the same time, and it is used as a food such as seasoning having a metabolism improving function. You can also do it.
カルニチンは、L−カルニチン、D−カルニチン、及びDL−カルニチンなどがある。これらのカルニチンは、塩または誘導体の形態のものを用いることもできる。また、カルニチンの塩も利用することができる。カルニチンの塩は、例えばカルニチンナトリウム塩、カルニチンカリウム塩、カルニチン酒石酸塩およびカルニチンフマル酸塩等がある(以下カルニチン類)。本発明はこれらのカルニチン類を単独または複数組み合わせて利用することができる。特にL−カルニチンは、体内にリジン及びメチオニンから合成される。さらに、牛肉、豚肉等の畜肉に含まれており、安全性の高い物質であるため、特に好ましく利用することができる。 Carnitine includes L-carnitine, D-carnitine, DL-carnitine and the like. These carnitines can also be used in the form of salts or derivatives. Carnitine salts can also be used. Examples of the carnitine salt include carnitine sodium salt, carnitine potassium salt, carnitine tartrate and carnitine fumarate (hereinafter referred to as carnitines). In the present invention, these carnitines can be used alone or in combination of two or more. In particular, L-carnitine is synthesized in the body from lysine and methionine. Further, since it is contained in livestock meat such as beef and pork and is a highly safe substance, it can be particularly preferably used.
本発明でいうグルタチオンは、還元型グルタチオン、酸化型グルタチオンあるいはこれらの混合物をいう。還元型グルタチオンとはγ − L − G l u − L − C y s − G l y の構造を有するトリペプチドを表し、酸化型グルタチオンとは還元型グルタチオン2 分子がS S 結合により結合したものである。グルタチオンの形態は、グルタチオンを有効成分として含有するものであれば何でもよい。 Glutathione as used in the present invention refers to reduced glutathione, oxidized glutathione, or a mixture thereof. Reduced glutathione represents a tripeptide having a structure of γ-L-G l u-L-Cy s-G l y, and oxidized glutathione is a substance in which two reduced glutathione molecules are bound by an SS bond. is there. The form of glutathione may be any form as long as it contains glutathione as an active ingredient.
グルタチオンは、例えば酵母や酵母エキス中に含むものを利用しても良い。グルタチオンを多く酵母としては、「ハイチオンコーボMG」(興人ライフサイエンス社製)、グルタチオンを含有する酵母エキスとしては「ハイチオンエキスYH」(興人ライフサイエンス社製)などがある。 As glutathione, for example, those contained in yeast or yeast extract may be used. Examples of yeasts containing a large amount of glutathione include "Haition Cobo MG" (manufactured by Kojin Life Science Co., Ltd.), and yeast extracts containing glutathione include "Haitiion Extract YH" (manufactured by Kojin Life Science Co., Ltd.).
本願では、前段のグルタチオン及びカルニチン類を有効成分として含むものを投与する。投与の方法は、特に限定されず、経口投与、静脈内、腹膜内もしくは皮下投与等の非経口投与をあげることができる。具体的には、錠剤、散剤、顆粒剤、丸剤、懸濁剤、乳剤、浸剤・煎剤、カプセル剤、シロップ剤、液剤、エリキシル剤、エキス剤、チンキ剤、流エキス剤等の経口剤、又は注射剤、点滴剤、クリーム剤、坐剤等の非経口剤のいずれでもよい。 In the present application, those containing glutathione and carnitines in the previous stage as active ingredients are administered. The method of administration is not particularly limited, and parenteral administration such as oral administration, intravenous administration, intraperitoneal administration, or subcutaneous administration can be mentioned. Specifically, oral preparations such as tablets, powders, granules, pills, suspensions, emulsions, soaking agents / decoctions, capsules, syrups, liquids, elixirs, extracts, tinctures, and intravenous extracts. Alternatively, it may be any parenteral preparation such as an injection, a drip, a cream, and a suppository.
本発明の投与量は、前述の機能が発現する量でれば特に限定されない。ヒトに投与する場合の投与量および投与回数は、投与形態、被投与者の年齢、体重等により異なるが、成人一日当り、グルタチオンを通常は5 0 m g 〜30g 、好ましくは100 mg〜1 0g、特に好ましくは200 mg〜3g、カルニチンは5mg〜5g 、好ましくは50mg〜2g、より好ましくは100mg〜1000mg、となるように一日一回乃至数回投与する。 The dose of the present invention is not particularly limited as long as it exhibits the above-mentioned functions. The dose and frequency of administration to humans vary depending on the dosage form, age, body weight, etc. of the recipient, but glutathione is usually 50 mg to 30 g, preferably 100 mg to 10 g per day for adults. , Especially preferably 200 mg to 3 g, carnitine 5 mg to 5 g, preferably 50 mg to 2 g, more preferably 100 mg to 1000 mg once or several times a day.
投与間隔は、特に限定されない。継続的に投与することが好ましい。通常は1 日間〜 1 年間、好ましくは1 週間〜3 ヶ月間である。なお、本発明の製剤は、ヒトだけでなく、ヒト以外の動物( 以下、非ヒト動物と略す)に対しても使用することができる。
The dosing interval is not particularly limited. It is preferable to administer continuously. It is usually 1 day to 1 year, preferably 1 week to 3 months. The preparation of the present invention can be used not only for humans but also for animals other than humans (hereinafter, abbreviated as non-human animals).
以下に実施例により本発明をさらに詳しく説明するが、本発明はこれらの実施例により限定されるものではない。 The present invention will be described in more detail below with reference to Examples, but the present invention is not limited to these Examples.
3T3-L1細胞を3x10^4 cells/ 2 mLになるように6 well plateに播種する。培養2日目、5日目に培地交換を行い、培養7日目に分化誘導培地に交換した。分化誘導培地で培養3日目にインスリン含有培地に変更し、2日毎に培地交換を行いながら12日間培養を続けた。なお、本発明品は分化誘導培地に交換するときから培養終了まで添加した。添加量は、グルタチオンのみ1000μg/ml、カルニチン 250、500μg/ml、グルタチオン1000μg/ml及びカルニチン250μg/ml、グルタチオン1000μg/ml及びカルニチン500μg/mlとした。培養12日目の細胞をオイルレッド染色にて脂肪滴の染色を行い、写真撮影後にイソプロパノールにて色素を抽出し吸光度490nmにて測定を行い、数値化した。結果は、図1に示す。また参考に細胞染色写真を図2に示す。 Seed 3T3-L1 cells on a 6-well plate to 3x10 ^ 4 cells / 2 mL. The medium was exchanged on the 2nd and 5th days of the culture, and the medium was exchanged for a differentiation-inducing medium on the 7th day of the culture. The culture medium was changed to an insulin-containing medium on the 3rd day of culturing with a differentiation-inducing medium, and the culturing was continued for 12 days while exchanging the medium every 2 days. The product of the present invention was added from the time of replacement with the differentiation-inducing medium to the end of culturing. The amount of glutathione added was 1000 μg / ml for glutathione only, 250 μg / ml for carnitine, 1000 μg / ml for glutathione and 250 μg / ml for carnitine, 1000 μg / ml for glutathione, and 500 μg / ml for carnitine. The cells on the 12th day of culture were stained with oil red staining for lipid droplets, and after photography, the dye was extracted with isopropanol and measured at an absorbance of 490 nm to quantify. The results are shown in FIG. A cell-stained photograph is shown in FIG. 2 for reference.
・ 分化誘導培地:
播種培地 100 mL
インスリン(終濃度 10 μg/mL) 1 mL
デキサメタゾン(終濃度 2.5 μM) 0.5 mL
イソブチルメチルキサンチン(終濃度 0.5mM) 0.1 mL
・ Differentiation induction medium:
Seed medium 100 mL
Insulin (final concentration 10 μg / mL) 1 mL
Dexamethasone (final concentration 2.5 μM) 0.5 mL
Isobutylmethylxanthine (final concentration 0.5 mM) 0.1 mL
・ インスリン含有培地
播種培地 100 mL
インスリン(終濃度 10 μg/mL) 1 mL
・ Insulin-containing medium 100 mL of seeding medium
Insulin (final concentration 10 μg / mL) 1 mL
・ オイルレッド染色(標準プロトコールに従って実施)
準備試薬:
1 Oil Red Oストック溶液:90 mg Oil Red Oを30 mLイソプロパノールに溶かすが、完全には解けない(遮光)
2 60%イソプロ:イソプロ:蒸留水(DW)=3:2 (90 mL:60 mL)
6 well plate染色:
1 染色液作成:ストック溶液:DW=3:2 (30mL:20mL)で混合し、0.45 μmフィルターでろ過し、沈殿除去
2 PBSで洗浄1回後、1mL 4%パラホルムアルデヒドを加えて、1hr 室温静置
3 DWで3回洗浄
4 染色液2 mL/Well、シェーカーでゆっくり振とうしながら、20 min 室温でインキュベート
5 DWで洗浄、5 min x3回
6 60%イソプロパノールで洗浄、5 min x3回
7 画像撮影
8 100%イソプロを1 mL加えて、5 minインキュベート
9 200 μL/Well移し、492 nm (490 nm)で測定(Blank=イソプロパノール200 μL)
・ Oil red dyeing (implemented according to standard protocol)
Preparation reagent:
1 Oil Red O stock solution: 90 mg Oil Red O is dissolved in 30 mL isopropanol, but it is not completely dissolved (shading).
2 60% Isopro: Isopro: Distilled water (DW) = 3: 2 (90 mL: 60 mL)
6 well plate staining:
1 Staining solution preparation: Stock solution: Mix with DW = 3: 2 (30 mL: 20 mL), filter with 0.45 μm filter, remove precipitate, wash once with 2 PBS, add 1 mL 4% paraformaldehyde, and room temperature for 1 hr. Stand still 3 Wash 3 times with DW 4 Stain solution 2 mL / Well, incubate at room temperature for 20 min while shaking slowly with shaker 5 Wash with DW, 5 min x 3 times 6 Wash with 60% isopropanol, 5 min x 3 times 7 Imaging 8 Add 1 mL of 100% isopro, incubate for 5 min, transfer 9 200 μL / Well, and measure at 492 nm (490 nm) (Blank = isopropanol 200 μL).
図1の結果より、L−カルニチン及びグルタチオンを添加した群では、同濃度の単独添加よりも相乗的に脂肪細胞への分化を抑制している。 From the results shown in FIG. 1, the group to which L-carnitine and glutathione were added synergistically suppressed the differentiation into adipocytes as compared with the addition of the same concentration alone.
カルニチン及びグルタチオンの脂肪細胞への分化抑制用組成物となる本発明品は、カルニチンの脂質代謝効果を活性化することが期待されるため、脂質代謝の促進剤、体脂肪蓄積防止剤などとして利用でき、生活習慣病の予防等に適用できる。 The product of the present invention, which is a composition for suppressing the differentiation of carnitine and glutathione into adipocytes, is expected to activate the lipid metabolism effect of carnitine, and is therefore used as a lipid metabolism promoter, a body fat accumulation inhibitor, etc. It can be applied to the prevention of lifestyle diseases.
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JP2002542191A (en) * | 1999-04-16 | 2002-12-10 | シグマ−タウ・ヘルスサイエンス・ソシエタ・ペル・アチオニ | Carnitine and glutathione-containing compositions useful for increasing glutathione absorption and enhancing its effect |
JP2007519678A (en) * | 2004-01-28 | 2007-07-19 | ネステク ソシエテ アノニム | Nutritional composition for improving skin condition and preventing skin diseases |
JP2008143811A (en) * | 2006-12-07 | 2008-06-26 | Nisshin Pharma Inc | Lipid metabolism promoting composition |
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