JP7106181B1 - Composition characterized by containing pine bark - Google Patents
Composition characterized by containing pine bark Download PDFInfo
- Publication number
- JP7106181B1 JP7106181B1 JP2022018236A JP2022018236A JP7106181B1 JP 7106181 B1 JP7106181 B1 JP 7106181B1 JP 2022018236 A JP2022018236 A JP 2022018236A JP 2022018236 A JP2022018236 A JP 2022018236A JP 7106181 B1 JP7106181 B1 JP 7106181B1
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- Prior art keywords
- fish
- pine bark
- elastin
- derived
- composition
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Abstract
【課題】血管の機能改善又は維持や、血管の機能、血液の性状、血流等の改善又は維持が可能な組成物を提供すること。【解決手段】松樹皮とドコサヘキサエン酸を含有する組成物、若しくは、松樹皮及び、γ－アミノ酪酸、並びにエイコサペンタエン酸、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有する組成物である。【選択図】図１An object of the present invention is to provide a composition capable of improving or maintaining vascular function, or improving or maintaining vascular function, blood properties, blood flow, and the like. A composition containing pine bark and docosahexaenoic acid, or a composition containing pine bark, γ-aminobutyric acid, and at least one selected from eicosapentaenoic acid, collagen, and elastin. [Selection drawing] Fig. 1
Description
特許法第３０条第２項適用 株式会社東洋新薬が消費者庁に刊行物を提出した日付：２０２１年３月１日，刊行物の情報を消費者庁が公開した日付：２０２１年４月２日，発行物名：株式会社東洋新薬による「フラバン」の機能性表示食品の届出書類，掲載アドレス：ｈｔｔｐｓ：／／ｗｗｗ．ｆｌｄ．ｃａａ．ｇｏ．ｊｐ／ｃａａｋｓ／ｃｓｓｃ０２／？ｒｅｃｏｒｄＳｅｑ＝４２１０６１５０５７０３０１Application of Article 30, Paragraph 2 of the Patent Act The date that Toyo Shinyaku Co., Ltd. submitted the publication to the Consumer Affairs Agency: March 1, 2021, the date that the Consumer Affairs Agency published the information in the publication: April 2, 2021 Japan, Publication name: Notification documents for food with functional claims for “Flavan” by Toyo Shinyaku Co., Ltd., Posting address: https://www. fld. caa. go. jp/caaks/cssc02/? recordSeq=42106150570301
特許法第３０条第２項適用 株式会社東洋新薬が消費者庁に刊行物を提出した日付：２０２１年６月２１日，刊行物の情報を消費者庁が公開した日付：２０２１年８月６日，発行物名：株式会社東洋新薬による「フラバン血管サポート」の機能性表示食品の届出書類，掲載アドレス：ｈｔｔｐｓ：／／ｗｗｗ．ｆｌｄ．ｃａａ．ｇｏ．ｊｐ／ｃａａｋｓ／ｃｓｓｃ０２／？ｒｅｃｏｒｄＳｅｑ＝４２１０８２００１８０２０１Application of Article 30, Paragraph 2 of the Patent Act Date of submission of publication by Toyo Shinyaku Co., Ltd. to the Consumer Affairs Agency: June 21, 2021 Date of publication information published by the Consumer Affairs Agency: August 6, 2021 Japan, Publication name: Notification documents for food with functional claims for “Flavan Vascular Support” by Toyo Shinyaku Co., Ltd., Posting address: https://www. fld. caa. go. jp/caaks/cssc02/? recordSeq=42108200180201
本発明は、松樹皮及び特定の他の素材を含有することを特徴とする組成物に関する。 The present invention relates to compositions characterized by containing pine bark and certain other materials.
食生活やライフスタイルの変化に伴って生活習慣病が増加している。このような生活習慣病として、近年は、高血圧症、狭心症、心筋梗塞、脳循環障害など、血管や血液に関連した疾患が増加傾向にある。
このような生活習慣病は慢性的な疾患であるため、その予防や治療には長期間を要する。従って、長期間にわたって安全かつ効果的に、血管の機能、血液の性状、血流等を改善する飲食品が求められている。例えば、血管柔軟性を向上し、血管内皮機能を改善する食品素材としては、ホップやクロロゲン酸が知られている（特許文献１、２参照）。
Lifestyle-related diseases are increasing with changes in eating habits and lifestyles. As such lifestyle-related diseases, diseases related to blood vessels and blood, such as hypertension, angina pectoris, myocardial infarction, and cerebral circulation disorders, have been increasing in recent years.
Since such lifestyle-related diseases are chronic diseases, their prevention and treatment require a long period of time. Therefore, there is a demand for foods and drinks that improve vascular function, blood properties, blood flow, etc. safely and effectively over a long period of time. For example, hops and chlorogenic acid are known as food materials that improve vascular flexibility and vascular endothelial function (see
本発明の課題は、血管の機能、血液の性状、血流等の改善又は維持が可能な組成物を提供することにある。 An object of the present invention is to provide a composition capable of improving or maintaining vascular function, blood properties, blood flow, and the like.
本発明者らは、松樹皮と及び特定の他の素材を組み合わせることにより、優れた血管柔軟性改善又は維持効果、優れた血管内皮機能改善又は維持効果、優れた血小板凝集抑制又は血小板凝集能維持効果又は優れた血流改善又は維持効果が得られることを見いだし、本発明を完成するに至った。 The present inventors have found that by combining pine bark and specific other materials, excellent vascular flexibility improvement or maintenance effect, excellent vascular endothelial function improvement or maintenance effect, excellent platelet aggregation inhibition or maintenance of platelet aggregation ability The present inventors have found that an effect or an excellent effect of improving or maintaining blood flow can be obtained, and have completed the present invention.
すなわち、本発明は、以下のとおりのものである。
［１］松樹皮を血管柔軟性改善又は維持の有効成分とする組成物であって、さらに、ドコサヘキサエン酸を含有することを特徴とする組成物。
［２］松樹皮を血管内皮機能改善又は維持の有効成分とする組成物であって、さらに、ドコサヘキサエン酸を含有することを特徴とする組成物。
［３］松樹皮を血小板凝集抑制又は血小板凝集能維持の有効成分とする組成物であって、さらに、ドコサヘキサエン酸を含有することを特徴とする組成物。
［４］松樹皮を血流改善又は維持の有効成分とする組成物であって、さらに、ドコサヘキサエン酸を含有することを特徴とする組成物。
［５］さらに、エイコサペンタエン酸を含有することを特徴とする［１］～［５］に記載の組成物。
［６］さらに、γ－アミノ酪酸を含有することを特徴とする［１］～［６］に記載の組成物。
［７］さらに、コラーゲン又はエラスチンを含有することを特徴とする［１］～［６］に記載の組成物。
［８］松樹皮及びドコサヘキサエン酸を含有することを特徴とする血管柔軟性改善又は維持用組成物。
［９］松樹皮及びドコサヘキサエン酸を含有することを特徴とする血管内皮機能改善又は維持用組成物。
［１０］松樹皮及びドコサヘキサエン酸を含有することを特徴とする血小板凝集抑制又は血小板凝集能維持用組成物。
［１１］松樹皮及びドコサヘキサエン酸を含有することを特徴とする血流改善又は維持用組成物。
［１２］さらに、エイコサペンタエン酸を含有することを特徴とする［８］～［１１］に記載の組成物。
［１３］さらに、γ－アミノ酪酸を含有することを特徴とする［８］～［１２］に記載の組成物。
［１４］さらに、コラーゲン又はエラスチンを含有することを特徴とする［８］～［１３］に記載の組成物。
［１５］松樹皮を血管柔軟性改善又は維持の有効成分とする組成物であって、さらに、γ－アミノ酪酸、並びにエイコサペンタエン酸、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有することを特徴とする組成物。
［１６］松樹皮を血管内皮機能改善又は維持の有効成分とする組成物であって、さらに、γ－アミノ酪酸、並びにエイコサペンタエン酸、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有することを特徴とする組成物。
［１７］松樹皮を血小板凝集抑制又は血小板凝集能維持の有効成分とする組成物であって、さらに、γ－アミノ酪酸、並びにエイコサペンタエン酸、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有することを特徴とする組成物。
［１８］松樹皮を血流改善又は維持の有効成分とする組成物であって、さらに、γ－アミノ酪酸、並びにエイコサペンタエン酸、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有することを特徴とする組成物。
［１９］松樹皮及び、γ－アミノ酪酸、並びにエイコサペンタエン酸、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有することを特徴とする血管柔軟性改善又は維持用組成物。
［２０］松樹皮及び、γ－アミノ酪酸、並びにエイコサペンタエン酸、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有することを特徴とする血管内皮機能改善又は維持用組成物。
［２１］松樹皮及び、γ－アミノ酪酸、並びにエイコサペンタエン酸、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有することを特徴とする血小板凝集抑制又は血小板凝集能維持用組成物。
［２２］松樹皮及び、γ－アミノ酪酸、並びにエイコサペンタエン酸、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有することを特徴とする血流改善又は維持用組成物。
That is, the present invention is as follows.
[1] A composition comprising pine bark as an active ingredient for improving or maintaining vascular flexibility, and further comprising docosahexaenoic acid.
[2] A composition comprising pine bark as an active ingredient for improving or maintaining vascular endothelial function, and further comprising docosahexaenoic acid.
[3] A composition comprising pine bark as an active ingredient for inhibiting platelet aggregation or maintaining platelet aggregation ability, and further comprising docosahexaenoic acid.
[4] A composition comprising pine bark as an active ingredient for improving or maintaining blood flow, and further comprising docosahexaenoic acid.
[5] The composition according to [1] to [5], further comprising eicosapentaenoic acid.
[6] The composition according to [1] to [6], further comprising γ-aminobutyric acid.
[7] The composition according to [1] to [6], further comprising collagen or elastin.
[8] A composition for improving or maintaining vascular flexibility, comprising pine bark and docosahexaenoic acid.
[9] A composition for improving or maintaining vascular endothelial function, comprising pine bark and docosahexaenoic acid.
[10] A composition for inhibiting platelet aggregation or maintaining platelet aggregation, comprising pine bark and docosahexaenoic acid.
[11] A composition for improving or maintaining blood flow, comprising pine bark and docosahexaenoic acid.
[12] The composition according to [8] to [11], further comprising eicosapentaenoic acid.
[13] The composition according to [8] to [12], further comprising γ-aminobutyric acid.
[14] The composition of [8] to [13], further comprising collagen or elastin.
[15] A composition containing pine bark as an active ingredient for improving or maintaining vascular flexibility, characterized by further containing γ-aminobutyric acid and at least one selected from eicosapentaenoic acid, collagen and elastin. composition.
[16] A composition containing pine bark as an active ingredient for improving or maintaining vascular endothelial function, characterized by further containing γ-aminobutyric acid and at least one selected from eicosapentaenoic acid, collagen and elastin. composition.
[17] A composition containing pine bark as an active ingredient for inhibiting platelet aggregation or maintaining platelet aggregation ability, and further containing γ-aminobutyric acid and at least one selected from eicosapentaenoic acid, collagen and elastin. A composition characterized by:
[18] A composition containing pine bark as an active ingredient for improving or maintaining blood flow, characterized by further containing γ-aminobutyric acid and at least one selected from eicosapentaenoic acid, collagen and elastin. composition.
[19] A composition for improving or maintaining vascular flexibility, comprising pine bark, γ-aminobutyric acid, and at least one selected from eicosapentaenoic acid, collagen, and elastin.
[20] A composition for improving or maintaining vascular endothelial function, comprising pine bark, γ-aminobutyric acid, and at least one selected from eicosapentaenoic acid, collagen and elastin.
[21] A composition for inhibiting platelet aggregation or maintaining platelet aggregation, comprising pine bark, γ-aminobutyric acid, and at least one selected from eicosapentaenoic acid, collagen, and elastin.
[22] A composition for improving or maintaining blood flow, comprising pine bark, γ-aminobutyric acid, and at least one selected from eicosapentaenoic acid, collagen, and elastin.
本発明の組成物は、血管柔軟性改善又は維持効果、血管内皮機能改善又は維持効果、血小板凝集抑制又は血小板凝集能維持効果及び血流改善又は維持効果の少なくとも１つの効果を奏する。 The composition of the present invention exhibits at least one effect of improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting platelet aggregation or maintaining platelet aggregation ability, and improving or maintaining blood flow.
本発明の組成物は、松樹皮とドコサヘキサエン酸、若しくは、松樹皮及び、γ－アミノ酪酸、並びにエイコサペンタエン酸、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有することを特徴とする。松樹皮とドコサヘキサエン酸を含有する場合、更に、エイコサペンタエン酸、γ－アミノ酪酸、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有してもよいが、エイコサペンタエン酸、γ－アミノ酪酸、コラーゲン及びエラスチンから選ばれる２種以上を含有することが好ましく、エイコサペンタエン酸、γ－アミノ酪酸、コラーゲン及びエラスチンから選ばれる３種以上を含有することがより好ましく、エイコサペンタエン酸、γ－アミノ酪酸、コラーゲン及びエラスチンの４種全てを含有することが特に好ましい。松樹皮及び、γ－アミノ酪酸、並びにエイコサペンタエン酸、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有する場合は、松樹皮及び、γ－アミノ酪酸とともに含有される、エイコサペンタエン酸、コラーゲン及びエラスチンから選ばれる素材は、２種以上を含有することがより好ましく、３種全てを含有することが特に好ましい。 The composition of the present invention is characterized by containing pine bark and docosahexaenoic acid, or pine bark and γ-aminobutyric acid, and at least one selected from eicosapentaenoic acid, collagen and elastin. When pine bark and docosahexaenoic acid are contained, at least one selected from eicosapentaenoic acid, γ-aminobutyric acid, collagen and elastin may be further contained, eicosapentaenoic acid, γ-aminobutyric acid, collagen and elastin It preferably contains two or more selected from eicosapentaenoic acid, γ-aminobutyric acid, more preferably three or more selected from collagen and elastin, eicosapentaenoic acid, γ-aminobutyric acid, collagen and It is particularly preferred to contain all four types of elastin. When pine bark and at least one selected from γ-aminobutyric acid and eicosapentaenoic acid, collagen and elastin are contained, eicosapentaenoic acid, collagen and elastin contained together with pine bark and γ-aminobutyric acid It is more preferable that the selected material contains two or more kinds, and it is particularly preferable that all three kinds are contained.
本発明の組成物は、血管柔軟性改善又は維持効果、血管内皮機能改善又は維持効果、血小板凝集抑制又は血小板凝集能維持効果及び血流改善又は維持効果の少なくとも１つの効果を奏し、松樹皮をこれらの効果を奏するための有効成分とする。本発明の組成物は、これらの効果を奏することから、血管柔軟性改善又は維持用組成物、血管内皮機能改善又は維持用組成物、血小板凝集抑制又は血小板凝集能維持用組成物、又は血流改善又は維持用組成物として用いることができる。 The composition of the present invention exhibits at least one effect of improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting platelet aggregation or maintaining platelet aggregation ability, and improving or maintaining blood flow. It is considered as an active ingredient for exhibiting these effects. Since the composition of the present invention exhibits these effects, it is a composition for improving or maintaining vascular flexibility, a composition for improving or maintaining vascular endothelial function, a composition for inhibiting platelet aggregation or maintaining platelet aggregation ability, or a composition for maintaining blood flow. It can be used as a remedial or maintenance composition.
ここで、本発明における改善又は維持とは、その性質や機能の低下抑制、維持及び向上を含む概念である。具体的には、血管柔軟性改善又は維持には、血管の柔軟性の低下抑制、維持及び向上を含む。血管内皮機能改善又は維持には、血管内皮機能の低下抑制、維持及び向上を含む。血流改善又は維持には、血流量の低下抑制、維持及び向上を含む。 Here, the improvement or maintenance in the present invention is a concept including suppression of deterioration, maintenance and improvement of properties and functions. Specifically, improvement or maintenance of vascular flexibility includes suppression of decrease in vascular flexibility, maintenance and improvement. Improving or maintaining vascular endothelial function includes suppression of deterioration, maintenance and improvement of vascular endothelial function. Improving or maintaining blood flow includes suppression of decrease, maintenance and improvement of blood flow.
以下、本発明の組成物に含まれる各成分について説明する。
［松樹皮］
本発明は、松樹皮を使用することを特徴とする。本発明で用いられる松樹皮の原料松としては、フランス海岸松（Ｐｉｎｕｓ ｐｉｎａｓｔｅｒ）、カラマツ、クロマツ、アカマツ、ヒメコマツ、ゴヨウマツ、チョウセンマツ、ハイマツ、リュウキュウマツ、ウツクシマツ、ダイオウマツ、シロマツ等を挙げられが、これらに限定されない。これらの中でも、より高い効果を得ることができる点から、フランス海岸松が好ましい。
Each component contained in the composition of the present invention is described below.
[Pine bark]
The present invention is characterized by using pine bark. Examples of the pine from which the pine bark is used in the present invention include French maritime pine (Pinus pinaster), larch, black pine, Japanese red pine, Japanese white pine, Japanese pine, Korean pine, creeping pine, Ryukyu pine, Japanese white pine, giant pine, white pine, and the like. , but not limited to. Among these, French maritime pine is preferable because higher effects can be obtained.
本発明においては、松樹皮を加工して用いることができ、松樹皮加工物としては、例えば、チップ状物、粉砕物、搾汁物、抽出物や、これらの乾燥粉末を挙げることができる。本発明において用いられる松樹皮は、製剤性を考慮すると、適用が容易であることから、粉砕物、搾汁物、抽出物又はこれらの乾燥粉末であることが好ましく、より高い効果を得ることができる点から、抽出物又はその乾燥粉末であることがより好ましい。松樹皮加工物は、当業者により通常知られている方法によって製造したものでもよいし、市場に流通しているものであってもよい。例えば、株式会社東洋新薬製の松樹皮抽出物を用いることができる。 In the present invention, pine bark can be processed and used, and examples of processed pine bark products include chips, pulverized products, squeezed products, extracts, and dried powders thereof. The pine bark used in the present invention is preferably pulverized, squeezed, extracted, or dried powder thereof because it is easy to apply in consideration of formulation properties, and higher effects can be obtained. From the point of view, it is more preferable to be an extract or a dry powder thereof. The processed pine bark may be produced by a method generally known by those skilled in the art, or may be commercially available. For example, a pine bark extract manufactured by Toyo Shinyaku Co., Ltd. can be used.
松樹皮抽出物を得る際に使用する抽出溶媒としては、例えば、水、有機溶媒、含水有機溶媒（含水エタノールといった含水アルコール）が挙げられる。有機溶媒としては、例えば、メタノール、エタノール、１－プロパノール、２－プロパノール、１－ブタノール、２－ブタノール、ブタン、アセトン、ヘキサン、シクロヘキサン、プロピレングリコール、含水エタノール、含水プロピレングリコール、エチルメチルケトン、グリセリン、酢酸メチル、酢酸エチル、ジエチルエーテル、ジクロロメタン、食用油脂、１，１，１，２－テトラフルオロエタン、及び１，１，２－トリクロロエテンが挙げられる。これらの水及び有機溶媒は単独で用いてもよいし、組み合わせて用いてもよい。抽出溶媒としては、水を用いることが好ましい。なお、抽出する際の溶媒の温度は、用いる溶媒の沸点以下であれば限定されない。 Examples of the extraction solvent used for obtaining the pine bark extract include water, organic solvents, and hydrous organic solvents (hydrous alcohol such as hydrous ethanol). Examples of organic solvents include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, butane, acetone, hexane, cyclohexane, propylene glycol, hydrous ethanol, hydrous propylene glycol, ethyl methyl ketone, glycerin. , methyl acetate, ethyl acetate, diethyl ether, dichloromethane, edible fats and oils, 1,1,1,2-tetrafluoroethane, and 1,1,2-trichloroethene. These water and organic solvents may be used alone or in combination. Water is preferably used as the extraction solvent. In addition, the temperature of the solvent at the time of extraction is not limited as long as it is equal to or lower than the boiling point of the solvent used.
松樹皮抽出物を得る方法については、特に限定はないが、例えば、加温抽出法、超臨界流体抽出法、液体二酸化炭素回分法、液体二酸化炭素還流法、超臨界二酸化炭素還流法等が挙げられる。また、複数の抽出方法を組み合わせてもよい。複数の抽出方法を組み合わせることにより、種々の組成の松樹皮抽出物を得ることが可能となる。 The method for obtaining the pine bark extract is not particularly limited, but examples include heating extraction method, supercritical fluid extraction method, liquid carbon dioxide batch method, liquid carbon dioxide reflux method, supercritical carbon dioxide reflux method, and the like. be done. Moreover, you may combine several extraction methods. By combining multiple extraction methods, it is possible to obtain pine bark extracts with various compositions.
超臨界流体抽出法とは、物質の気液の臨界点（臨界温度、臨界圧力）を超えた状態の流体である超臨界流体を用いて抽出を行う方法である。超臨界流体としては、二酸化炭素、エチレン、プロパン、亜酸化窒素（笑気ガス）等が用いられるが、二酸化炭素が好ましく用いられる。 The supercritical fluid extraction method is a method of performing extraction using a supercritical fluid, which is a fluid in a state exceeding the critical point (critical temperature, critical pressure) of gas and liquid of a substance. As the supercritical fluid, carbon dioxide, ethylene, propane, nitrous oxide (laughing gas), etc. are used, and carbon dioxide is preferably used.
超臨界流体抽出法では、目的成分を超臨界流体によって抽出する抽出工程と、目的成分と超臨界流体を分離する分離工程とを行う。分離工程では、圧力変化による抽出分離、温度変化による抽出分離、吸着剤、吸収剤を用いた抽出分離のいずれを行ってもよい。 In the supercritical fluid extraction method, an extraction step of extracting a target component with a supercritical fluid and a separation step of separating the target component and the supercritical fluid are performed. In the separation step, any of extraction and separation by pressure change, extraction and separation by temperature change, and extraction and separation using an adsorbent or an absorbent may be performed.
また、エントレーナー添加法による超臨界流体抽出を行ってもよい。この方法は、抽出流体に、例えば、エタノール、プロパノール、ｎ－ヘキサン、アセトン、トルエン、その他の脂肪族低級アルコール類、脂肪族炭化水素類、芳香族炭化水素類、ケトン類を２～２０Ｗ／Ｖ％程度添加し、この流体を用いて超臨界流体抽出を行うことによって、ＯＰＣ（Ｏｌｉｇｏｍｅｒｉｃ ｐｒｏａｎｔｈｏｃｙａｎｉｄｉｎ：オリゴメリック・プロアントシアニジン）、カテキン類等の目的とする抽出物の抽出溶媒に対する溶解度を飛躍的に上昇させる、あるいは分離の選択性を増強させる方法であり、効率的な松樹皮抽出物を得る方法である。 Alternatively, supercritical fluid extraction may be performed by an entrainer addition method. This method uses, for example, ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, and ketones in the extraction fluid at 2 to 20 W/V. % and performing supercritical fluid extraction using this fluid, the solubility of the target extract such as OPC (oligomeric proanthocyanidin) and catechins in the extraction solvent is dramatically increased. or enhance the selectivity of separation, and is a method for obtaining an efficient pine bark extract.
超臨界流体抽出法は、比較的低い温度で操作できるため、高温で変質・分解する物質にも適用できるという利点、抽出流体が残留しないという利点、溶媒の循環利用が可能であるため、脱溶媒工程等が省略でき、工程がシンプルになるという利点がある。 Supercritical fluid extraction can be operated at relatively low temperatures, so it has the advantage of being applicable to substances that degrade or decompose at high temperatures. There is an advantage that the process can be omitted and the process becomes simple.
上記の抽出により得られた松樹皮抽出物を、カラム法又はバッチ法により精製することが安全性の面から好ましい。カラム法としては、例えば、ダイヤイオンＨＰ－２０、Ｓｅｐｈａｄｅｘ－ＬＨ２０、キチン等の吸着性担体を用いた精製方法が挙げられる。 From the viewpoint of safety, it is preferable to purify the pine bark extract obtained by the above extraction by a column method or a batch method. The column method includes, for example, a purification method using an adsorptive carrier such as Diaion HP-20, Sephadex-LH20 and chitin.
本発明における松樹皮抽出物は、主な成分の一つとして、プロアントシアニジンを含有する。プロアントシアニジンは、フラバン－３－オール及び／又はフラバン－３，４－ジオールを構成単位とする重合度が２以上の縮重合体からなる化合物群である。 The pine bark extract in the present invention contains proanthocyanidins as one of the main components. Proanthocyanidins are a group of compounds consisting of condensation polymers having a degree of polymerization of 2 or more and having flavan-3-ol and/or flavan-3,4-diol as structural units.
本発明における松樹皮抽出物は、プロアントシアニジンとして重合度が２以上の縮重合体が含有されていることが好ましい。特に、重合度が低い縮重合体が多く含まれるプロアントシアニジンが好ましい。重合度の低い縮重合体としては、例えば、重合度が２～３０の縮重合体（２～３０量体）であり、より高い効果を得ることができる点から、重合度が２～１０の縮重合体（２～１０量体）が好ましく、重合度が２～４の縮重合体（２～４量体）が特に好ましい。重合度が２～４の縮重合体（２～４量体）の中でも、プロシアニジンＢ１及びプロシアニジンＢ３を含有することが好ましい。プロシアニジンＢ１は、（－）エピカテキンと（＋）カテキンとがＣ４－Ｃ８結合した二量体であり、プロシアニジンＢ３は、（＋）カテキンと（＋）カテキンとがＣ４－Ｃ８結合した二量体である。 The pine bark extract in the present invention preferably contains a polycondensation product having a degree of polymerization of 2 or more as proanthocyanidins. In particular, proanthocyanidins containing a large amount of polycondensates with a low degree of polymerization are preferred. The polycondensate with a low degree of polymerization is, for example, a polycondensate with a degree of polymerization of 2 to 30 (dimeric to 30-mer). Condensation polymers (2- to 10-mers) are preferred, and condensation polymers having a degree of polymerization of 2 to 4 (2- to 4-mers) are particularly preferred. Among polycondensates (dimers to tetramers) having a degree of polymerization of 2 to 4, it is preferable to contain procyanidin B1 and procyanidin B3. Procyanidin B1 is a C4-C8-linked dimer of (−) epicatechin and (+) catechin, and procyanidin B3 is a C4-C8-linked dimer of (+) catechin and (+) catechin is.
本発明の組成物におけるプロシアニジンは、例えば、ＨＰＬＣにて分析することができる。 Procyanidins in the composition of the present invention can be analyzed, for example, by HPLC.
［ドコサヘキサエン酸］
ドコサヘキサエン酸（以下、「ＤＨＡ」とも言う）とは、ｎ－３脂肪酸の多価不飽和脂肪酸の一つであり、６つの二重結合を含む２２個の炭素鎖をもつカルボン酸である。本発明におけるＤＨＡとしては、魚類や微生物などの天然物由来のもの、合成したもの等を用いることができ、特に限定されないが、安全性の点から、天然物由来のものが好ましく、天然物由来の中でも、魚類由来のものが好ましい。魚類由来のものとしては、例えば、魚油や肝油が挙げられる。
[docosahexaenoic acid]
Docosahexaenoic acid (hereinafter also referred to as “DHA”) is one of polyunsaturated n-3 fatty acids, and is a carboxylic acid having a 22-carbon chain containing 6 double bonds. As the DHA in the present invention, those derived from natural products such as fish and microorganisms, synthesized products, and the like can be used, and are not particularly limited. Among them, those derived from fish are preferable. Those derived from fish include, for example, fish oil and cod liver oil.
本発明の組成物におけるＤＨＡの量は、例えば、ガスクロマトグラフィーにて分析することが出来る。 The amount of DHA in the composition of the present invention can be analyzed, for example, by gas chromatography.
［エイコサペンタエン酸］
エイコサペンタエン酸（以下、「ＥＰＡ」とも言う）とは、ｎ－３脂肪酸の多価不飽和脂肪酸の一つであり、５つの二重結合を含む２０個の炭素鎖をもつカルボン酸である。本発明におけるＥＰＡとしては、魚類や微生物などの天然物由来のもの、合成したもの等を用いることができ、特に限定されないが、安全性の点から、天然物由来のものが好ましく、天然物由来の中でも、魚類由来のものが好ましい。魚類由来のものとしては、例えば、魚油や肝油が挙げられる。
[Eicosapentaenoic acid]
Eicosapentaenoic acid (hereinafter also referred to as “EPA”) is one of polyunsaturated n-3 fatty acids, and is a carboxylic acid having a 20-carbon chain containing five double bonds. As the EPA in the present invention, those derived from natural products such as fish and microorganisms, synthesized products, and the like can be used, and are not particularly limited. Among them, those derived from fish are preferable. Those derived from fish include, for example, fish oil and cod liver oil.
本発明の組成物におけるＥＰＡの量は、例えば、ガスクロマトグラフィーにて分析することが出来る。 The amount of EPA in the composition of the present invention can be analyzed, for example, by gas chromatography.
［γ－アミノ酪酸］
γ－アミノ酪酸（以下、「ＧＡＢＡ」とも言う）とは、動植物界に広く分布するアミノ酸の一種であり、哺乳類の脳や髄に存在する抑制系の神経伝達物質である。本発明におけるＧＡＢＡとしては、合成物や茶、大麦若葉、発芽玄米などの植物由来物、乳酸菌などの微生物による発酵由来物を用いることができ、安全性の点から、茶、大麦若葉、発芽玄米などの植物由来物および乳酸菌などの微生物による発酵由来物が好ましく、乳酸菌などの微生物による発酵由来物がより好ましい。
[γ-aminobutyric acid]
γ-Aminobutyric acid (hereinafter also referred to as “GABA”) is a kind of amino acid widely distributed in the animal and plant kingdoms, and is an inhibitory neurotransmitter present in the brain and marrow of mammals. As GABA in the present invention, synthetic products, plant-derived products such as tea, young barley leaves, and sprouted brown rice, and products derived from fermentation by microorganisms such as lactic acid bacteria can be used. Plant-derived substances such as lactic acid bacteria and fermentation-derived substances by microorganisms such as lactic acid bacteria are preferable, and fermentation-derived substances by microorganisms such as lactic acid bacteria are more preferable.
本発明の組成物におけるＧＡＢＡの量は、例えば、アミノ酸自動分析装置にて分析することが出来る。 The amount of GABA in the composition of the present invention can be analyzed using, for example, an automatic amino acid analyzer.
［コラーゲン］
コラーゲンとは。動物の皮膚、骨、軟骨等に多く含まれるタンパク質の一種である。本発明におけるコラーゲンとしては、コラーゲンタンパク質の他、コラーゲンタンパク質を加水分解して得られるコラーゲンペプチドや、コラーゲン分子をプロテアーゼで処理し、テロペプチド部分を取り除いたアテロコラーゲンが含まれる。本発明におけるコラーゲンは動物由来物や合成物を用いることができ、特に限定されないが、より高い効果を得ることができる点から、動物由来物が好ましく、動物由来物の中でも、魚類由来が好ましい。
[collagen]
What is collagen? It is a kind of protein abundantly contained in animal skin, bone, cartilage, and the like. Collagen in the present invention includes, in addition to collagen protein, collagen peptides obtained by hydrolyzing collagen proteins, and atelocollagen obtained by treating collagen molecules with protease to remove telopeptide portions. Collagen in the present invention can be animal-derived or synthesized, and is not particularly limited, but is preferably animal-derived, and among animal-derived collagen, fish-derived is preferable in terms of obtaining higher effects.
本発明におけるコラーゲンの平均分子量（重量平均分子量）としては、特に制限されるものではないが、１００～１０００００が好ましく、５００～５００００がより好ましく、より高い効果を得ることができる点から、１０００～１００００が特に好ましい。 The average molecular weight (weight average molecular weight) of collagen in the present invention is not particularly limited, but is preferably 100 to 100,000, more preferably 500 to 50,000. 10,000 is particularly preferred.
［エラスチン］
エラスチンとは、哺乳類、鳥類、魚類等、特に哺乳動物の大動脈、項靭帯、黄色靭帯、肺、皮膚、子宮、弾性軟骨等に、コラーゲンと共に存在し、弾性を有する主要蛋白質であり、別名として、弾性繊維とも称される。本発明におけるエラスチンとしては、水溶性エラスチンの他に加水分解エラスチン、α－エラスチン、κ－エラスチン及びエラスチンペプチド等も含まれる。
[Elastin]
Elastin is a major elastic protein that exists together with collagen in mammals, birds, fish, etc., particularly mammalian aorta, ligamentum flavum, lungs, skin, uterus, elastic cartilage, etc. Also called elastic fibers. Elastin in the present invention includes not only water-soluble elastin but also hydrolyzed elastin, α-elastin, κ-elastin and elastin peptides.
本発明におけるエラスチンは、動物性生体組織、例えばブタ、ウシ、ウマ、ヒツジ等の哺乳動物、カツオ、マグロ、ハマチ、サケ等の魚類の結合組織から、酸又はアルカリでエラスチンを加水分解し、又は酵素処理することによって抽出することができる。本発明におけるエラスチンは、天然物由来のもの、合成したもの等を用いることができ、特に限定されないが、より高い効果を得ることができる点から、魚類由来のものが好ましく、魚類の中でも、カツオ又はマグロ由来のものがより好ましく、カツオ由来が特に好ましい。 Elastin in the present invention is obtained by hydrolyzing elastin with an acid or alkali from the connective tissue of mammals such as pigs, cows, horses, and sheep, or fish such as bonito, tuna, yellowtail, and salmon, or It can be extracted by enzymatic treatment. Elastin in the present invention may be derived from natural products, synthesized or the like, and is not particularly limited. Alternatively, those derived from tuna are more preferred, and those derived from bonito are particularly preferred.
本発明の組成物は、例えば、医薬品（医薬部外品を含む）や、特定保健用食品、栄養機能食品、機能性表示食品等の所定機関より効能の表示が認められた機能性食品などのいわゆる健康食品等として用いることができる。 The composition of the present invention is, for example, pharmaceuticals (including quasi-drugs), food for specified health uses, food with nutrient function claims, functional food, etc. It can be used as a so-called health food or the like.
本発明の組成物は、血管柔軟性改善又は維持用組成物、血管内皮機能改善又は維持用組成物、血小板凝集抑制又は血小板凝集能維持用組成物及び血流改善又は維持血流改善又は維持又は維持用組成物の少なくとも１つとして用いることができ、かかる血管柔軟性改善又は維持用組成物、血管内皮機能改善又は維持用組成物、血小板凝集抑制又は血小板凝集能維持用組成物、血流改善又は維持組成物としては、松樹皮とドコサヘキサエン酸、若しくは、松樹皮及び、γ－アミノ酪酸、並びにエイコサペンタエン酸、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有し、それぞれ血管柔軟性改善又は維持、血管内皮機能改善又は維持、血小板凝集抑制又は血小板凝集能維持、血流改善又は維持の機能が発揮される点において、製品として他の製品と区別することができるものであれば特に制限されるものではなく、例えば、本発明に係る製品の本体、包装、説明書、宣伝物（広告媒体）のいずれかに、血管柔軟性改善又は維持、血管内皮機能改善又は維持、血小板凝集抑制又は血小板凝集能維持、血流改善又は維持の機能を表示したものが本発明の範囲に含まれる。 The composition of the present invention includes a composition for improving or maintaining vascular flexibility, a composition for improving or maintaining vascular endothelial function, a composition for inhibiting platelet aggregation or maintaining platelet aggregation ability, and improving or maintaining blood flow. It can be used as at least one maintenance composition, such as a composition for improving or maintaining vascular flexibility, a composition for improving or maintaining vascular endothelial function, a composition for inhibiting platelet aggregation or maintaining platelet aggregation ability, and improving blood flow. Alternatively, the maintenance composition contains pine bark and docosahexaenoic acid, or pine bark and γ-aminobutyric acid, and at least one selected from eicosapentaenoic acid, collagen, and elastin to improve or maintain blood vessel flexibility, respectively, Products that can be distinguished from other products in terms of improving or maintaining vascular endothelial function, inhibiting platelet aggregation or maintaining platelet aggregation ability, and improving or maintaining blood flow are particularly restricted. However, for example, the main body, packaging, instructions, or advertising material (advertising media) of the product according to the present invention may include improvement or maintenance of vascular flexibility, improvement or maintenance of vascular endothelial function, inhibition of platelet aggregation, or platelet aggregation ability Any indication of the function of maintenance, blood flow improvement or maintenance is included in the scope of the present invention.
なお、本発明の組成物は、松樹皮が有効成分として表示されているものであってもよいが、松樹皮が有効成分として表示されているものに限られない。例えば、有効成分が表示されていないものであってもよい。また、一般的な食品であっても、機能・用途を示唆して製造販売されるものは本発明の範囲に含まれる。例えば、摂取した人の個人的感想として機能・用途に言及する体験談をホームページ等に掲載して販売される食品が挙げられる。 The composition of the present invention may be one labeled as an active ingredient with pine bark, but is not limited to one labeled with pine bark as an active ingredient. For example, the active ingredient may not be displayed. In addition, even general foods that are manufactured and sold with suggested functions and uses are included in the scope of the present invention. For example, there is a food that is sold by posting on a website or the like a testimonial about its functions and uses as a personal impression of a person who has ingested it.
具体的に、いわゆる健康食品においては、血管柔軟性改善又は維持用組成物においては、例えば、「加齢とともに低下する血管の柔軟性の維持に役立つ」、「血管を締め付けた後の血管の拡張度を高める」、「血管を締め付けた後の血管の拡張度を維持する」、「血管柔軟性を高める」、「血管柔軟性を維持する」、「血管のしなやかさを高める」、「血管のしなやかさを維持する」、「血管機能を高める」、「血管機能を維持する」等を表示したものを例示することができる。血管内皮機能改善又は維持用組成物においては、例えば、「血管内皮機能を高める」、「血管内皮機能を維持する」、「加齢によって衰える動脈の血管内皮機能を高める」、「加齢によって衰える動脈の血管内皮機能を維持する」、「血管機能を高める」、「血管機能を維持する」等を表示したものを例示することができる。また、血小板凝集抑制又は血小板凝集能維持用組成物においては、例えば、「血小板の凝集を抑制する」、「血小板の凝集を防ぐ」、「血小板凝集能を維持する」、「血液のサラサラ度の維持に役立つ」、「血液の流動性（血小板凝集能）の維持に役立つ」「血液の流れやすさ（血小板凝集能）の維持に役立つ」等を表示したものを例示することができる。また、血流改善又は維持用組成物においては、「血液の流動性の維持に役立つ」、「血液の流れやすさの維持に役立つ」、「血流を改善する」、「血流を維持する」、「健やかな血流を保つ」、「健やかな末梢血流を保つ」「低下した末梢の血流量を上昇させて正常に戻す」「低下した血流を正常に整える」「低下した末梢血流を正常に整える」、「血のめぐりを良くする」、「冷えを改善する」、「むくみが気になる方に」、「肌の色が気になる方に」、「目のくまが気になる方に」、「男性機能のサポートに」、「男性の活力に」等を表示したものを例示することができる。 Specifically, in so-called health foods, in compositions for improving or maintaining blood vessel flexibility, there are "increase the degree of blood vessel expansion", "maintain the dilation of blood vessels after tightening", "enhance blood vessel flexibility", "maintain blood vessel flexibility", "enhance blood vessel flexibility", "blood vessel Examples include those displaying "maintain suppleness", "improve vascular function", "maintain vascular function", and the like. In the composition for improving or maintaining vascular endothelial function, for example, "enhance vascular endothelial function", "maintain vascular endothelial function", "enhance vascular endothelial function of arteries that decline with age", " Examples include those labeled with "maintain artery endothelial function", "enhance vascular function", "maintain vascular function", and the like. In addition, in the composition for suppressing platelet aggregation or maintaining platelet aggregation ability, for example, "inhibit platelet aggregation", "prevent platelet aggregation", "maintain platelet aggregation ability", "improve blood smoothness" Examples include those labeled as "useful for maintenance", "helpful for maintaining blood fluidity (platelet aggregation)", "helpful for maintaining ease of blood flow (platelet aggregation)", and the like. In addition, in the composition for improving or maintaining blood flow, "useful for maintaining blood fluidity", "useful for maintaining ease of blood flow", "improving blood flow", "maintaining blood flow", ”, “Maintain healthy blood flow”, “Maintain healthy peripheral blood flow”, “Increase decreased peripheral blood flow to normal”, “Regulate decreased blood flow”, “Reduced peripheral blood Regulates blood flow", "Improve blood circulation", "Improve coldness", "Those who are concerned about swelling", "Those who are concerned about skin color", "Dark circles" For those who are concerned,” “for male function support,” “for male vitality,” etc. can be exemplified.
本発明の組成物の形態は特に限定されず、任意の形態とすることができる。例えば、経口的な使用に適した形態、具体的には、粉末状、粒状、顆粒状、錠状、液状、ジェル状、ペースト状、ハードカプセルやソフトカプセルのようなカプセル状、カプレット状、タブレット状、ゲル状、ゼリー状、グミ状、ウエハース状、ビスケット状、クッキー状、ケーキ状、チュアブル状、シロップ状、スティック状などの各形態が挙げられる。また、使用する形態に合わせて、種々の賦形剤、結合剤、滑沢剤、安定剤、希釈剤、増量剤、増粘剤、ゲル化剤、乳化剤、着色料、香料、甘味料、添加剤などを配合することができる。 The form of the composition of the present invention is not particularly limited, and can be any form. For example, forms suitable for oral use, specifically powders, granules, granules, tablets, liquids, gels, pastes, capsules such as hard capsules and soft capsules, caplets, tablets, Examples include gel, jelly, gummy, wafer, biscuit, cookie, cake, chewable, syrup, and stick forms. In addition, various excipients, binders, lubricants, stabilizers, diluents, bulking agents, thickeners, gelling agents, emulsifiers, coloring agents, flavors, sweeteners, additives, etc. Agents and the like can be added.
本発明の組成物は、摂取が容易である点から、顆粒状、錠状、カプセル状、液状が好ましく、顆粒状、錠状、カプセル状がより好ましい。ここで、顆粒状とは粉末を造粒したものをいい、直接飲用してもよく、水などの液体に溶かして飲用してもよい。また、ジェル状とは水とゲル化剤を含有し、粘性又は弾性を有する状態のものをいう。 The composition of the present invention is preferably in the form of granules, tablets, capsules, or liquid, more preferably in the form of granules, tablets, or capsules, from the viewpoint of ease of ingestion. Here, granules refer to granulated powders, which may be drunk directly or dissolved in a liquid such as water. In addition, the term “gel-like” refers to a state in which water and a gelling agent are contained and the substance is viscous or elastic.
本発明の組成物における松樹皮の含有量としては、その効果の奏する範囲で適宜含有させればよい。例えば、本発明の組成物中に、乾物換算で、松樹皮を０．０００１～５０質量％含有させることができ、０．００１～４０質量％含有させることが好ましく、０．０１～３０質量％含有させることがより好ましい。 The content of pine bark in the composition of the present invention may be appropriately contained within a range in which the effect is exhibited. For example, the composition of the present invention can contain 0.0001 to 50% by mass, preferably 0.001 to 40% by mass, and 0.01 to 30% by mass of pine bark in terms of dry matter. It is more preferable to contain.
本発明の組成物におけるＤＨＡの含有量としては、その効果の奏する範囲で適宜含有させればよい。例えば、本発明の組成物中に、乾物換算で、ＤＨＡを０．０００１～５０質量％含有させることができ、０．０００５～４０質量％含有させることが好ましく、０．００１～３０質量％含有させることがより好ましい。 The content of DHA in the composition of the present invention may be appropriately contained within a range in which the effect is exhibited. For example, the composition of the present invention can contain 0.0001 to 50% by mass of DHA, preferably 0.0005 to 40% by mass, and more preferably 0.001 to 30% by mass, in terms of dry matter. It is more preferable to let
本発明の組成物におけるＥＰＡの含有量としては、その効果の奏する範囲で適宜含有させればよい。例えば、本発明の組成物中に、乾物換算で、ＥＰＡを０．０００１～５０質量％含有させることができ、０．０００５～４０質量％含有させることが好ましく、０．００１～３０質量％含有させることがより好ましい。 The content of EPA in the composition of the present invention may be appropriately contained within a range in which its effect is exhibited. For example, the composition of the present invention can contain 0.0001 to 50% by mass, preferably 0.0005 to 40% by mass, and more preferably 0.001 to 30% by mass of EPA in terms of dry matter. It is more preferable to let
本発明の組成物におけるＧＡＢＡの含有量としては、その効果の奏する範囲で適宜含有させればよい。例えば、本発明の組成物中に、乾物換算で、ＧＡＢＡを０．０００１～５０質量％含有させることができ、０．０００５～４０質量％含有させることが好ましく、０．００１～３０質量％含有させることがより好ましい。 The content of GABA in the composition of the present invention may be appropriately contained within a range in which the effect is exhibited. For example, the composition of the present invention can contain 0.0001 to 50% by mass of GABA in terms of dry matter, preferably 0.0005 to 40% by mass, and 0.001 to 30% by mass. It is more preferable to let
本発明の組成物におけるコラーゲンの含有量としては、その効果の奏する範囲で適宜含有させればよい。例えば、本発明の組成物中に、乾物換算で、コラーゲンを０．００００１～３０質量％含有させることができ、０．０００１～２０質量％含有させることが好ましく、０．００１～１０質量％含有させることがより好ましい。 The content of collagen in the composition of the present invention may be appropriately contained within a range in which its effect is exhibited. For example, the composition of the present invention can contain 0.00001 to 30% by mass, preferably 0.0001 to 20% by mass, and more preferably 0.001 to 10% by mass of collagen in terms of dry matter. It is more preferable to let
本発明の組成物におけるエラスチンの含有量としては、その効果の奏する範囲で適宜含有させればよい。例えば、本発明の組成物中に、乾物換算で、エラスチンを０．００００１～３０質量％含有させることができ、０．０００１～２０質量％含有させることが好ましく、０．００１～１０質量％含有させることがより好ましい。 The content of elastin in the composition of the present invention may be appropriately contained within a range in which the effect is exhibited. For example, the composition of the present invention can contain 0.00001 to 30% by mass, preferably 0.0001 to 20% by mass, and more preferably 0.001 to 10% by mass of elastin in terms of dry matter. It is more preferable to let
松樹皮とＤＨＡの配合質量比としては、例えば、１：０．００００１～５００であり、１：０．００００５～２００であることが好ましく、１：０．００１～１００であることがより好ましい。 The mass ratio of pine bark and DHA is, for example, 1:0.00001-500, preferably 1:0.00005-200, and more preferably 1:0.001-100.
松樹皮とＥＰＡの配合質量比としては、例えば、１：０．００００１～５００であり、１：０．００００５～２００であることが好ましく、１：０．００１～１００であることがより好ましい。 The mass ratio of pine bark to EPA is, for example, 1:0.00001 to 500, preferably 1:0.00005 to 200, and more preferably 1:0.001 to 100.
松樹皮とＧＡＢＡの配合質量比としては、例えば、１：０．００００１～５００であり、１：０．００００５～２００であることが好ましく、１：０．００１～１００であることがより好ましい。 The mass ratio of pine bark and GABA is, for example, 1:0.00001-500, preferably 1:0.00005-200, and more preferably 1:0.001-100.
松樹皮とコラーゲンの配合質量比としては、例えば、１：０．００００１～５００であり、１：０．００００５～２００であることが好ましく、１：０．００１～１００であることがより好ましい。 The mass ratio of pine bark to collagen is, for example, 1:0.00001 to 500, preferably 1:0.00005 to 200, and more preferably 1:0.001 to 100.
松樹皮とエラスチンの配合質量比としては、例えば、１：０．００００１～５００であり、１：０．００００５～２００であることが好ましく、１：０．００１～１００であることがより好ましい。 The mass ratio of pine bark to elastin is, for example, 1:0.00001-500, preferably 1:0.00005-200, and more preferably 1:0.001-100.
本発明の組成物における松樹皮、ＤＨＡ、ＥＰＡ、ＧＡＢＡ、コラーゲン及びエラスチンの合計含有量としては、その効果の奏する範囲で適宜含有させればよい。例えば、本発明の組成物中に、乾物換算で、０．０００１～１００質量％含有させることができ、０．００１～７０質量％含有させることが好ましく、０．０１～５０質量％含有させることがより好ましい。 The total content of pine bark, DHA, EPA, GABA, collagen and elastin in the composition of the present invention may be appropriately contained within the range in which the effect is exhibited. For example, the composition of the present invention can contain 0.0001 to 100% by mass, preferably 0.001 to 70% by mass, and preferably 0.01 to 50% by mass in terms of dry matter. is more preferred.
本発明における組成物の摂取量としては特に制限はないが、より高い効果を得ることができる点から、松樹皮の摂取量が、成人の１日当たり、１０ｍｇ以上となるように摂取することが好ましく、３０ｍｇ以上となるように摂取することがより好ましく、６０ｍｇ以上となるように摂取することがさらに好ましい。その上限は、例えば、３００ｍｇであり、好ましくは２５０ｍｇであり、より好ましくは２００ｍｇである。 The intake amount of the composition in the present invention is not particularly limited, but it is preferable that the intake amount of pine bark is 10 mg or more per day for adults in order to obtain a higher effect. , more preferably 30 mg or more, more preferably 60 mg or more. The upper limit is, for example, 300 mg, preferably 250 mg, more preferably 200 mg.
本発明の組成物は、松樹皮の１日の摂取量が上記摂取量となるように適宜設計すればよく、１回で上記摂取量を摂取する態様であってもよいし、複数回に分けて上記摂取量を摂取する態様であってもよい。すなわち、例えば、１つの容器に、又は２～４の複数の容器に分けて、１日分として収容することができる。
また、本発明の組成物の１日の摂取量は、例えば、本発明の組成物が固形剤（粉末状、粒状、顆粒状、錠状、カプセル状、チュアブル状など）である場合には、０．０５～５０ｇとなるように摂取することが好ましく、０．１～１０ｇとなるように摂取することがより好ましく、０．２～５ｇとなるように摂取することがさらに好ましい。また、例えば、本発明の組成物が液剤（液状、ジェル状、ペースト状など）である場合には、１０～１０００ｇとなるように摂取することが好ましく、３０～７５０ｇとなるように摂取することがより好ましく、５０～５００ｇとなるように摂取することがさらに好ましい。
The composition of the present invention may be appropriately designed so that the daily intake of pine bark is the above intake. It is also possible to adopt a mode in which the above intake amount is ingested. That is, for example, it can be contained in one container or divided into a plurality of containers of 2 to 4 for one day.
In addition, the daily intake of the composition of the present invention is, for example, when the composition of the present invention is a solid formulation (powder, granule, granule, tablet, capsule, chewable, etc.), It is preferable to ingest 0.05 to 50 g, more preferably 0.1 to 10 g, and even more preferably 0.2 to 5 g. Further, for example, when the composition of the present invention is a liquid (liquid, gel, paste, etc.), it is preferably taken in an amount of 10 to 1000 g, more preferably 30 to 750 g. is more preferable, and it is even more preferable to take 50 to 500 g.
本発明の組成物は、必要に応じて、松樹皮、ＤＨＡ、ＥＰＡ、ＧＡＢＡ、コラーゲン、エラスチン以外の他の成分を添加して、公知の方法によって製造することができる。 The composition of the present invention can be produced by a known method by adding ingredients other than pine bark, DHA, EPA, GABA, collagen and elastin, if necessary.
以下、本発明を実施例に基づいてさらに詳細に説明するが、本発明はこれに限定されるものではない。 EXAMPLES The present invention will be described in more detail below based on examples, but the present invention is not limited to these.
＜試験１ ＮＯ合成酵素遺伝子発現量の評価＞
一酸化窒素（ＮＯ）合成酵素遺伝子発現量について評価した。
血管内皮でＮＯ合成酵素（ｅＮＯＳ）により産生されたＮＯが拡散されて血管平滑筋に届くと、筋肉が弛緩されて血管が拡張する。ＮＯ合成酵素遺伝子発現量が増加すると、ＮＯ合成酵素量が増加し、ＮＯ産生量が増加するため、血管柔軟性改善又は維持、血管内皮機能改善又は維持及び血流改善又は維持が期待できる。
以上より、ＮＯ合成酵素遺伝子発現量を評価することで、血管柔軟性改善又は維持効果、血管内皮機能改善又は維持効果及び血流改善又は維持効果を評価することができる。
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Nitric oxide (NO) synthase gene expression level was evaluated.
When NO produced by NO synthase (eNOS) in the vascular endothelium diffuses and reaches vascular smooth muscle, the muscle relaxes and blood vessels dilate. When the NO synthase gene expression level increases, the NO synthase level increases and the NO production increases, so improvement or maintenance of vascular flexibility, improvement or maintenance of vascular endothelial function, and improvement or maintenance of blood flow can be expected.
As described above, by evaluating the NO synthase gene expression level, the effect of improving or maintaining vascular flexibility, the effect of improving or maintaining vascular endothelial function, and the effect of improving or maintaining blood flow can be evaluated.
［被験物質］
松樹皮としてプロシアニジンＢ１及びプロシアニジンＢ３を含有するフランス海岸松の松樹皮の熱水抽出物、コラーゲンとして魚由来のコラーゲンペプチド（平均分子量：約２０００）、エラスチンとしてカツオ由来のエラスチンを使用した。松樹皮、ＤＨＡ、ＥＰＡ、ＧＡＢＡ、コラーゲン、エラスチンはいずれも市販のものを使用した。
[Test substance]
A hot water extract of pine bark of French maritime pine containing procyanidin B1 and procyanidin B3 was used as pine bark, fish-derived collagen peptide (average molecular weight: about 2000) was used as collagen, and bonito-derived elastin was used as elastin. Pine bark, DHA, EPA, GABA, collagen, and elastin were all commercially available.
下記表１及び表２の割合となるように、ＤＭＳＯで溶解し、添加濃度でＤＭＳＯが０．５％になるようにＥｎｄｏｔｈｅｌｉａｌ Ｃｅｌｌ Ｇｒｏｗｔｈ Ｍｅｄｉｕｍ ２（ＥＧＭ－２）培地（Ｌｏｎｚａ製）で希釈することで、実施例１、２及び比較例１～３の被験物質を調製した。 Dissolve in DMSO to achieve the proportions shown in Tables 1 and 2 below, and dilute with Endothelial Cell Growth Medium 2 (EGM-2) medium (manufactured by Lonza) so that the added concentration of DMSO is 0.5%. The test substances of Examples 1 and 2 and Comparative Examples 1-3 were prepared.
ヒト臍帯静脈内皮細胞（ＨＵＶＥＣ：Ｌｏｎｚａ製）をＥＧＭ－２培地で培養した。コラーゲンコートされた９６ウェルプレートに前記の細胞を１×１０４ｃｅｌｌｓ／ｗｅｌｌとなるように１００μＬ／ｗｅｌｌで播種し、３７℃、５容量％ＣＯ２インキュベーター内で、２４時間前培養した。各ｗｅｌｌより培地を除去後、表１の被験物質含有培地を１００μＬ／ｗｅｌｌ添加し、２４時間培養した。
Human umbilical vein endothelial cells (HUVEC: manufactured by Lonza) were cultured in EGM-2 medium. The cells were seeded at 100 μL/well in a collagen-coated 96-well plate at 1×10 4 cells/well, and precultured at 37° C. in a 5 vol % CO 2 incubator for 24 hours. After removing the medium from each well, 100 μL/well of the test substance-containing medium shown in Table 1 was added and cultured for 24 hours.
［ＮＯ合成酵素遺伝子発現量の測定］
各ｗｅｌｌより培地を除去後、ＰＢＳで１回洗浄し、ＲＮｅａｓｙ Ｍｉｎｉ Ｋｉｔ（ＱＩＡＧＥＮ製）を用いてＲＮＡを回収した。得られたＲＮＡより、Ｏｎｅ Ｓｔｅｐ ＴＢＧｒｅｅｎ（登録商標） ＰｒｉｍｅＳｃｒｉｐｔ ＲＴ－ＰＣＲ ＫｉｔＩＩ（Ｔａｋａｒａ製）を用いてリアルタイムＰＣＲを実施した。ＮＯＳ３（ｅＮＯＳ）のプライマー（Ｔａｋａｒａ製）を用いて、ＮＯＳ３（ｅＮＯＳ）の遺伝子発現量を測定した。内在性コントロールとして、ＧＡＰＤＨのプライマー（ＱＩＡＧＥＮ製）を用いて、ＧＡＰＤＨの遺伝子発現量を測定した。
[Measurement of NO synthase gene expression level]
After removing the medium from each well, the cells were washed once with PBS, and RNA was recovered using RNeasy Mini Kit (manufactured by QIAGEN). Real-time PCR was performed on the obtained RNA using One Step TBGreen (registered trademark) PrimeScript RT-PCR Kit II (manufactured by Takara). The NOS3 (eNOS) gene expression level was measured using a NOS3 (eNOS) primer (manufactured by Takara). As an endogenous control, GAPDH gene expression levels were measured using GAPDH primers (manufactured by QIAGEN).
［ＮＯ合成酵素遺伝子発現量の評価］
表１の試験群において、松樹皮のみを投与した群（比較例１）の発現量を１とした場合の、ＮＯ合成酵素遺伝子発現量の相対値を算出した。結果を図１に示す。
[Evaluation of NO synthase gene expression level]
In the test groups shown in Table 1, the relative value of the NO synthase gene expression level was calculated when the expression level of the group to which only pine bark was administered (Comparative Example 1) was set to 1. The results are shown in FIG.
［ＮＯ合成酵素遺伝子発現量の評価］
表２の試験群において、松樹皮とＥＰＡを投与した群（比較例３）の発現量を１とした場合の、ＮＯ合成酵素遺伝子発現量の相対値を算出した。結果を図２に示す。
[Evaluation of NO synthase gene expression level]
In the test groups shown in Table 2, relative values of NO synthase gene expression levels were calculated when the expression level of the group to which pine bark and EPA were administered (Comparative Example 3) was set to 1. The results are shown in FIG.
図１に示すように、松樹皮とＤＨＡを投与した群（実施例１）は、松樹皮のみを投与した群（比較例１）及びＤＨＡのみを投与した群（比較例２）と比べて、ＮＯ合成酵素遺伝子発現量の増加が認められた。したがって、松樹皮とＤＨＡを組み合わせることにより、ＮＯ合成酵素遺伝子発現量の増加がみられることから、優れた血管柔軟性改善又は維持効果、優れた血管内皮機能改善又は維持効果、及び優れた血流改善又は維持効果を得ることができる。 As shown in FIG. 1, the group administered with pine bark and DHA (Example 1) was compared with the group administered with pine bark alone (Comparative Example 1) and the group administered with DHA alone (Comparative Example 2). An increase in the NO synthase gene expression level was observed. Therefore, by combining pine bark and DHA, an increase in the NO synthase gene expression level is observed, so that excellent vascular flexibility improvement or maintenance effect, excellent vascular endothelial function improvement or maintenance effect, and excellent blood flow An improvement or maintenance effect can be obtained.
また、図２に示すように、松樹皮とＤＨＡを含む投与した群（実施例２）より、松樹皮とＤＨＡとＥＰＡを投与した群（実施例３）が、松樹皮とＤＨＡとＥＰＡを投与した群（実施例３）より、松樹皮とＤＨＡとＥＰＡとＧＡＢＡを投与した群（実施例５）が、松樹皮とＤＨＡとＥＰＡとＧＡＢＡを投与した群（実施例５）より、松樹皮とＤＨＡとＥＰＡとコラーゲンとエラスチンを投与した群（実施例８）が、松樹皮とＤＨＡとＥＰＡとコラーゲンとエラスチンを投与した群（実施例８）より、松樹皮とＤＨＡとＥＰＡとＧＡＢＡとコラーゲンとエラスチンを投与した群（実施例９）が、ＮＯ合成酵素遺伝子発現量の増加により優れることが認められた。このことから、松樹皮とＤＨＡに、さらに、ＥＰＡ、ＧＡＢＡ、コラーゲン及びエラスチンから選ばれる少なくとも１種を組み合わせることにより、より優れた血管柔軟性改善又は維持効果、より優れた血管内皮機能改善又は維持効果、及びより優れた血流改善又は維持効果を得ることができ、ＥＰＡ、ＧＡＢＡ、コラーゲン及びエラスチンから選ばれる２種以上を組み合わせることにより、さらに優れた血管柔軟性改善又は維持効果、さらに優れた血管内皮機能改善又は維持効果、及びさらに優れた血流改善又は維持効果を得ることができ、ＥＰＡ、ＧＡＢＡ、コラーゲン及びエラスチンから選ばれる３種以上を組み合わせることにより、よりさらに優れた血管柔軟性改善又は維持効果、よりさらに優れた血管内皮機能改善又は維持効果、及びよりさらに優れた血流改善又は維持効果を得ることができ、ＥＰＡ、ＧＡＢＡ、コラーゲン及びエラスチンの４種を組み合わせることにより、極めて優れた血管柔軟性改善又は維持効果、極めて優れた血管内皮機能改善又は維持効果、及び極めて優れた血流改善又は維持効果を得ることができる。 Further, as shown in FIG. 2, the group administered with pine bark, DHA and EPA (Example 3) was administered with pine bark, DHA and EPA from the group administered with pine bark and DHA (Example 2). From the group (Example 3) administered with pine bark, DHA, EPA and GABA (Example 5), from the group administered with pine bark, DHA, EPA and GABA (Example 5), pine bark and The group to which DHA, EPA, collagen and elastin were administered (Example 8) was higher than the group to which pine bark, DHA, EPA, collagen and elastin were administered (Example 8). It was confirmed that the group to which elastin was administered (Example 9) was superior in increasing the NO synthase gene expression level. Therefore, by combining pine bark and DHA with at least one selected from EPA, GABA, collagen and elastin, it is possible to improve or maintain vascular flexibility and improve or maintain vascular endothelial function. EPA, GABA, collagen and elastin can be combined to obtain a more excellent blood flow improvement or maintenance effect, and a more excellent blood vessel flexibility improvement or maintenance effect, and a further excellent blood flow improvement or maintenance effect. A vascular endothelial function improving or maintaining effect and a further excellent blood flow improving or maintaining effect can be obtained, and a combination of 3 or more selected from EPA, GABA, collagen and elastin further improves blood vessel flexibility. or a maintenance effect, an even more excellent vascular endothelial function improvement or maintenance effect, and an even more excellent blood flow improvement or maintenance effect can be obtained. vascular flexibility improvement or maintenance effect, extremely excellent vascular endothelial function improvement or maintenance effect, and extremely excellent blood flow improvement or maintenance effect can be obtained.
また、松樹皮とＧＡＢＡとＥＰＡを投与した群（実施例４）は、松樹皮とＥＰＡを含む投与した群（比較例３）及び松樹皮とＧＡＢＡを投与した群（比較例４）より、ＮＯ合成酵素遺伝子発現量の増加に優れることが認められた。
松樹皮とＧＡＢＡとコラーゲンとエラスチンを投与した群（実施例６）及び松樹皮とＧＡＢＡとＥＰＡとコラーゲンとエラスチンを投与した群（実施例７）は、松樹皮とＥＰＡを含む投与した群（比較例３）、松樹皮とＧＡＢＡを投与した群（比較例４）、及び松樹皮とコラーゲンとエラスチンを投与した群（比較例５）より、ＮＯ合成酵素遺伝子発現量の増加に優れることが認められた。
さらに、松樹皮とＧＡＢＡとＥＰＡを投与した群（実施例４）より、松樹皮とＧＡＢＡとコラーゲンとエラスチンを投与した群（実施例６）が、松樹皮とＧＡＢＡとコラーゲンとエラスチンを投与した群（実施例６）より、松樹皮とＧＡＢＡとＥＰＡとコラーゲンとエラスチンを投与した群（実施例７）が、ＮＯ合成酵素遺伝子発現量の増加により優れることが認められた。
以上のことから、松樹皮及びＧＡＢＡ、並びにＥＰＡ、コラーゲン及びエラスチンから選ばれる少なくとも１種を組み合わせることにより、優れた血管柔軟性改善又は維持効果、優れた血管内皮機能改善又は維持効果、及び優れた血流改善又は維持効果を得ることができ、松樹皮及びＧＡＢＡ、並びにＥＰＡ、コラーゲン及びエラスチンから選ばれる２種以上を組み合わせることにより、より優れた血管柔軟性改善又は維持効果、より優れた血管内皮機能改善又は維持効果、及びより優れた血流改善又は維持効果を得ることができ、松樹皮及びＧＡＢＡ、並びにＥＰＡ、コラーゲン及びエラスチンの３種を組み合わせることによりさらに優れた血管柔軟性改善又は維持効果、よりさらに優れた血管内皮機能改善又は維持効果、及びよりさらに優れた血流改善又は維持効果を得ることができる。
In addition, the group administered with pine bark, GABA and EPA (Example 4) had a higher NO than the group administered with pine bark and EPA (Comparative Example 3) and the group administered with pine bark and GABA (Comparative Example 4) It was found to be excellent in increasing the synthase gene expression level.
The group administered with pine bark, GABA, collagen, and elastin (Example 6) and the group administered with pine bark, GABA, EPA, collagen, and elastin (Example 7) were compared with the group administered with pine bark and EPA (comparison Example 3), the group administered with pine bark and GABA (Comparative Example 4), and the group administered with pine bark, collagen and elastin (Comparative Example 5) were found to be superior in increasing the NO synthase gene expression level. rice field.
Furthermore, from the group administered with pine bark, GABA and EPA (Example 4), the group administered with pine bark, GABA, collagen and elastin (Example 6) was the group administered with pine bark, GABA, collagen and elastin. From (Example 6), it was confirmed that the group to which pine bark, GABA, EPA, collagen and elastin were administered (Example 7) was superior in increasing the NO synthase gene expression level.
From the above, by combining at least one selected from pine bark and GABA, and EPA, collagen and elastin, excellent vascular flexibility improvement or maintenance effect, excellent vascular endothelial function improvement or maintenance effect, and excellent Blood flow improvement or maintenance effect can be obtained, and by combining two or more selected from pine bark and GABA, and EPA, collagen and elastin, more excellent blood vessel flexibility improvement or maintenance effect and more excellent vascular endothelium A function improvement or maintenance effect and a more excellent blood flow improvement or maintenance effect can be obtained, and a combination of pine bark and GABA, and EPA, collagen and elastin provides an even more excellent blood vessel flexibility improvement or maintenance effect. , an even more excellent vascular endothelial function improving or maintaining effect and an even more excellent blood flow improving or maintaining effect can be obtained.
＜試験２ プロスタグランジンＩ２産生量の評価＞
プロスタグランジンＩ２（ＰＧＩ２）産生量について評価した。
血管内皮でプロスタグランジンＩ２が産生し、拡散されて血管平滑筋に届くと、筋肉が弛緩されて血管が拡張する。また、プロスタグランジンＩ２には、血小板の凝集を抑制する作用がある。プロスタグランジンＩ２産生量が増加することで、血管柔軟性改善又は維持、血管内皮機能改善又は維持、血小板凝集抑制又は血小板凝集能維持、及び血流改善又は維持が期待できる。
以上より、プロスタグランジンＩ２産生量を評価することで、血管柔軟性改善又は維持効果、血管内皮機能改善又は維持効果、血小板凝集抑制又は血小板凝集能維持効果、及び血流改善又は維持効果を評価することができる。プロスタグランジンＩ２は半減期が短いため、プロスタグランジンＩ２産生量の評価として、プロスタグランジンＩ２の代謝産物である６－ケトプロスタグランジンＦ１αを評価した。
<Test 2 Evaluation of prostaglandin I2 production>
Prostaglandin I 2 (PGI 2 ) production was evaluated.
When prostaglandin I2 is produced in the vascular endothelium and diffuses to reach the vascular smooth muscle, it relaxes the muscle and dilates the blood vessel. In addition, prostaglandin I2 has the effect of suppressing platelet aggregation. An increase in prostaglandin I2 production can be expected to improve or maintain vascular flexibility, improve or maintain vascular endothelial function, inhibit platelet aggregation or maintain platelet aggregation ability, and improve or maintain blood flow.
From the above, by evaluating the amount of prostaglandin I2 produced, vascular flexibility improvement or maintenance effect, vascular endothelial function improvement or maintenance effect, platelet aggregation inhibition or platelet aggregation ability maintenance effect, and blood flow improvement or maintenance effect can be evaluated. Since prostaglandin I2 has a short half-life, 6-ketoprostaglandin F1α , which is a metabolite of prostaglandin I2 , was evaluated as an evaluation of prostaglandin I2 production.
［被験物質］
被験物質は、試験１と同様の方法で、表３及び表４に示すものを調製した。
[Test substance]
The test substances shown in Tables 3 and 4 were prepared in the same manner as in
［細胞培養］
細胞培養は、試験１と同様の方法で行った。
[Cell culture]
Cell culture was performed in the same manner as in
［プロスタグランジンＩ２産生量の測定］
各ｗｅｌｌより培地を回収し、６－ｋｅｔｏ Ｐｒｏｓｔａｇｌａｎｄｉｎ Ｆ１α ＥＬＩＳＡキット（Ｃａｙｍａｎ製）を用いて培地中の６－ケトプロスタグランジンＦ１α量を測定し、プロスタグランジンＩ２産生量を評価した。
[Measurement of prostaglandin I2 production]
The medium was collected from each well, and the amount of 6-keto prostaglandin F1α in the medium was measured using a 6-keto Prostaglandin F1α ELISA kit (manufactured by Cayman) to evaluate prostaglandin I2 production.
［プロスタグランジンＩ２産生量の評価］
表３の試験群において、松樹皮抽出物のみを投与した群（比較例６）の産生量を１とした場合の、プロスタグランジンＩ２産生量の相対値を算出した。結果を図３に示す。
[Evaluation of prostaglandin I2 production]
Among the test groups shown in Table 3, relative values of prostaglandin I2 production were calculated when the production of the group (Comparative Example 6) to which only the pine bark extract was administered was set to 1. The results are shown in FIG.
表４の試験群において、松樹皮抽出物とＥＰＡを投与した群（比較例８）の産生量を１とした場合の、プロスタグランジンＩ２産生量の相対値を算出した。結果を図４に示す。 In the test groups shown in Table 4, relative values of prostaglandin I2 production were calculated when the production of the group (Comparative Example 8) to which the pine bark extract and EPA were administered was set to 1. The results are shown in FIG.
図３に示すように、松樹皮とＤＨＡを投与した群（実施例１０）は、松樹皮のみを投与した群（比較例６）及びＤＨＡのみを投与した群（比較例７）と比べて、プロスタグランジンＩ２産生量の増加が認められた。したがって、松樹皮とＤＨＡを組み合わせることにより、プロスタグランジンＩ２産生量の増加がみられることから、優れた血管柔軟性改善又は維持効果、優れた血管内皮機能改善又は維持効果、優れた血小板凝集抑制又は血小板凝集能維持効果、及び優れた血流改善又は維持効果を得ることができる。 As shown in FIG. 3, the group administered with pine bark and DHA (Example 10) was compared with the group administered with pine bark alone (Comparative Example 6) and the group administered with DHA alone (Comparative Example 7). An increase in prostaglandin I2 production was noted. Therefore, by combining pine bark and DHA, an increase in the amount of prostaglandin I2 production is observed, so that excellent vascular flexibility improvement or maintenance effect, excellent vascular endothelial function improvement or maintenance effect, and excellent platelet aggregation It is possible to obtain an effect of suppressing or maintaining platelet aggregation ability, and an excellent effect of improving or maintaining blood flow.
また、図４に示すように、松樹皮とＤＨＡを含む投与した群（実施例１１）より、松樹皮とＤＨＡとＥＰＡを投与した群（実施例１２）が、松樹皮とＤＨＡとＥＰＡを投与した群（実施例１２）より、松樹皮とＤＨＡとＥＰＡとＧＡＢＡを投与した群（実施例１４）が、松樹皮とＤＨＡとＥＰＡとＧＡＢＡを投与した群（実施例１４）より、松樹皮とＤＨＡとＥＰＡとコラーゲンとエラスチンを投与した群（実施例１７）が、松樹皮とＤＨＡとＥＰＡとコラーゲンとエラスチンを投与した群（実施例１７）より、松樹皮とＤＨＡとＥＰＡとＧＡＢＡとコラーゲンとエラスチンを投与した群（実施例１８）が、プロスタグランジンＩ２産生量の増加により優れることが認められた。このことから、松樹皮とＤＨＡに、さらに、ＥＰＡ、ＧＡＢＡ、コラーゲン及びエラスチンから選ばれる少なくとも１種を組み合わせることにより、より優れた血管柔軟性改善又は維持効果、より優れた血管内皮機能改善又は維持効果、より優れた血小板凝集抑制又は血小板凝集能維持効果、及びより優れた血流改善又は維持効果を得ることができ、ＥＰＡ、ＧＡＢＡ、コラーゲン及びエラスチンから選ばれる２種以上を組み合わせることにより、さらに優れた血管柔軟性改善又は維持効果、さらに優れた血管内皮機能改善又は維持効果、さらに優れた血小板凝集抑制又は血小板凝集能維持効果、及びさらに優れた血流改善又は維持効果を得ることができ、ＥＰＡ、ＧＡＢＡ、コラーゲン及びエラスチンから選ばれる３種以上を組み合わせることにより、よりさらに優れた血管柔軟性改善又は維持効果、よりさらに優れた血管内皮機能改善又は維持効果、よりさらに優れた血小板凝集抑制又は血小板凝集能維持効果、及びよりさらに優れた血流改善又は維持効果を得ることができ、ＥＰＡ、ＧＡＢＡ、コラーゲン及びエラスチンの４種を組み合わせることにより、極めて優れた血管柔軟性改善又は維持効果、極めて優れた血管内皮機能改善又は維持効果、極めて優れた血小板凝集抑制又は血小板凝集能維持効果、及び極めて優れた血流改善又は維持効果を得ることができる。 Further, as shown in FIG. 4, the group administered with pine bark, DHA and EPA (Example 12) was administered with pine bark, DHA and EPA from the group administered with pine bark and DHA (Example 11). From the group administered with pine bark, DHA, EPA and GABA (Example 14), the group administered with pine bark, DHA, EPA and GABA (Example 14) was treated with pine bark and The group administered with DHA, EPA, collagen, and elastin (Example 17) was superior to the group administered with pine bark, DHA, EPA, collagen, and elastin (Example 17), with pine bark, DHA, EPA, GABA, and collagen. The elastin-administered group (Example 18) was found to be superior in terms of increased prostaglandin I2 production. Therefore, by combining pine bark and DHA with at least one selected from EPA, GABA, collagen and elastin, it is possible to improve or maintain vascular flexibility and improve or maintain vascular endothelial function. effect, more excellent platelet aggregation inhibition or platelet aggregation ability maintenance effect, and more excellent blood flow improvement or maintenance effect can be obtained, and by combining two or more selected from EPA, GABA, collagen and elastin, further An excellent vascular flexibility improvement or maintenance effect, a further excellent vascular endothelial function improvement or maintenance effect, a further excellent platelet aggregation inhibition or platelet aggregation function maintenance effect, and a further excellent blood flow improvement or maintenance effect can be obtained, By combining three or more selected from EPA, GABA, collagen and elastin, even more excellent vascular flexibility improvement or maintenance effect, even more excellent vascular endothelial function improvement or maintenance effect, even more excellent platelet aggregation inhibition or It is possible to obtain platelet aggregation maintenance effect and even more excellent blood flow improvement or maintenance effect, and by combining EPA, GABA, collagen and elastin, extremely excellent blood vessel flexibility improvement or maintenance effect, extremely An excellent vascular endothelial function improving or maintaining effect, an extremely excellent platelet aggregation inhibiting or platelet aggregation function maintaining effect, and an extremely excellent blood flow improving or maintaining effect can be obtained.
また、松樹皮とＧＡＢＡとＥＰＡを投与した群（実施例１３）は、松樹皮とＥＰＡを含む投与した群（比較例８）及び松樹皮とＧＡＢＡを投与した群（比較例９）より、プロスタグランジンＩ２産生量の増加に優れることが認められた。
松樹皮とＧＡＢＡとコラーゲンとエラスチンを投与した群（実施例１５）及び松樹皮とＧＡＢＡとＥＰＡとコラーゲンとエラスチンを投与した群（実施例１６）は、松樹皮とＥＰＡを含む投与した群（比較例８）、松樹皮とＧＡＢＡを投与した群（比較例９）、及び松樹皮とコラーゲンとエラスチンを投与した群（比較例１０）より、プロスタグランジンＩ２産生量の増加に優れることが認められた。
さらに、松樹皮とＧＡＢＡとＥＰＡを投与した群（実施例１３）より、松樹皮とＧＡＢＡとコラーゲンとエラスチンを投与した群（実施例１５）が、松樹皮とＧＡＢＡとコラーゲンとエラスチンを投与した群（実施例１５）より、松樹皮とＧＡＢＡとＥＰＡとコラーゲンとエラスチンを投与した群（実施例１６）が、プロスタグランジンＩ２産生量の増加により優れることが認められた。
以上のことから、松樹皮及びＧＡＢＡ、並びにＥＰＡ、コラーゲン及びエラスチンから選ばれる少なくとも１種を組み合わせることにより、優れた血管柔軟性改善又は維持効果、優れた血管内皮機能改善又は維持効果、優れた血小板凝集抑制又は血小板凝集能維持効果、及び優れた血流改善又は維持効果を得ることができ、松樹皮及びＧＡＢＡ、並びにＥＰＡ、コラーゲン及びエラスチンから選ばれる２種以上を組み合わせることにより、より優れた血管柔軟性改善又は維持効果、より優れた血管内皮機能改善又は維持効果、より優れた血小板凝集抑制又は血小板凝集能維持効果、及びより優れた血流改善又は維持効果を得ることができ、松樹皮及びＧＡＢＡ、並びにＥＰＡ、コラーゲン及びエラスチンの３種を組み合わせることによりさらに優れた血管柔軟性改善又は維持効果、よりさらに優れた血管内皮機能改善又は維持効果、よりさらに優れた血小板凝集抑制又は血小板凝集能維持効果、及び、よりさらに優れた血流改善又は維持効果を得ることができる。
In addition, the group administered with pine bark, GABA, and EPA (Example 13) was more prostagenic than the group administered with pine bark and EPA (Comparative Example 8) and the group administered with pine bark and GABA (Comparative Example 9). It was found to be superior in increasing the amount of grandin I2 production.
The group administered with pine bark, GABA, collagen, and elastin (Example 15) and the group administered with pine bark, GABA, EPA, collagen, and elastin (Example 16) were compared with the group administered with pine bark and EPA (comparison Example 8), the group administered with pine bark and GABA (Comparative Example 9), and the group administered with pine bark, collagen and elastin (Comparative Example 10) were found to be superior in increasing prostaglandin I2 production. was taken.
Furthermore, from the group administered with pine bark, GABA and EPA (Example 13), the group administered with pine bark, GABA, collagen and elastin (Example 15) was the group administered with pine bark, GABA, collagen and elastin. From (Example 15), it was confirmed that the group to which pine bark, GABA, EPA, collagen and elastin were administered (Example 16) was superior due to the increase in prostaglandin I2 production.
From the above, by combining pine bark and GABA, and at least one selected from EPA, collagen and elastin, an excellent vascular flexibility improvement or maintenance effect, an excellent vascular endothelial function improvement or maintenance effect, and an excellent platelet Aggregation suppression or platelet aggregation maintenance effect, and excellent blood flow improvement or maintenance effect can be obtained, and by combining two or more selected from pine bark and GABA, EPA, collagen and elastin, more excellent blood vessels Flexibility improvement or maintenance effect, better vascular endothelial function improvement or maintenance effect, better platelet aggregation inhibition or platelet aggregation ability maintenance effect, and better blood flow improvement or maintenance effect can be obtained, and pine bark and A combination of GABA and EPA, collagen and elastin provides even better vascular flexibility improvement or maintenance effect, better vascular endothelial function improvement or maintenance effect, better platelet aggregation suppression or platelet aggregation ability maintenance. effect and even better blood flow improvement or maintenance effect can be obtained.
［製造例１－４］（顆粒剤の製造）
表５の配合の通り、松樹皮とＤＨＡ、若しくは、松樹皮及び、ＧＡＢＡ、並びにＥＰＡ、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有する顆粒剤を製造した。製造例１－４に記載の顆粒剤は、１日あたり３ｇを摂取すればよく、１００ｍｌの水などの溶媒に溶かして摂取してもよく、溶かさずにそのまま摂取してもよい。製造例１－４のいずれの顆粒剤も、血管柔軟性改善又は維持、血管内皮機能改善又は維持、血小板凝集抑制又は血小板凝集能維持、及び血流改善又は維持に有効であり、経口組成物として有用である。
[Production Example 1-4] (Production of granules)
Granules containing at least one selected from pine bark and DHA, or pine bark and GABA, EPA, collagen and elastin were produced according to the formulations shown in Table 5. The granules described in Production Examples 1-4 may be ingested at a dose of 3 g per day, and may be ingested after being dissolved in a solvent such as 100 ml of water, or may be ingested without being dissolved. Any of the granules of Production Examples 1-4 is effective for improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting platelet aggregation or maintaining platelet aggregation ability, and improving or maintaining blood flow, and is an oral composition. Useful.
［製造例５－８］（錠剤の製造）
表６の配合にて、松樹皮とＤＨＡ、若しくは、松樹皮及び、ＧＡＢＡ、並びにＥＰＡ、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有する錠剤を製造した。錠剤は、錠径８ｍｍφ、錠厚４．５ｍｍ、重量２５０ｍｇ、硬度５ｋｇｆ以上で製造した。製造例５－８に記載の錠剤は１日あたり２粒を摂取すればよく、１００ｍｌの水などと共に摂取することができる。製造例５－８のいずれの錠剤も、血管柔軟性改善又は維持、血管内皮機能改善又は維持、血小板凝集抑制又は血小板凝集能維持、及び血流改善又は維持に有効であり、経口組成物として有用である。
[Production Example 5-8] (Production of tablets)
Tablets containing at least one selected from pine bark and DHA, or pine bark and GABA, EPA, collagen and elastin were produced according to the formulation shown in Table 6. Tablets were manufactured to have a tablet diameter of 8 mmφ, a tablet thickness of 4.5 mm, a weight of 250 mg, and a hardness of 5 kgf or more. Two tablets described in Production Examples 5-8 should be taken per day, and can be taken with 100 ml of water or the like. All tablets of Production Examples 5-8 are effective for improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting platelet aggregation or maintaining platelet aggregation ability, and improving or maintaining blood flow, and are useful as oral compositions. is.
［製造例９－１２］（ソフトカプセルの製造）
表７の配合の内容物を、ゼラチンを含む被膜で被包することで、松樹皮とＤＨＡ、若しくは、松樹皮及び、ＧＡＢＡ、並びにＥＰＡ、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有するソフトカプセルを製造した。ソフトカプセルは１粒３００ｍｇで製造した。１日あたり２粒摂取すればよく、１００ｍｌの水などと共に摂取することができる。また、製造例９－１２のいずれのソフトカプセルも、血管柔軟性改善又は維持、血管内皮機能改善又は維持、血小板凝集抑制又は血小板凝集能維持、及び血流改善又は維持に有効であり、経口組成物として有用である。
[Production Example 9-12] (Production of soft capsules)
A soft capsule containing at least one selected from pine bark and DHA, or pine bark and GABA, EPA, collagen and elastin is formed by encapsulating the contents of the formulation of Table 7 with a film containing gelatin. manufactured. Soft capsules were manufactured with 300 mg per tablet. It suffices to take 2 tablets per day, which can be taken with 100 ml of water or the like. In addition, any of the soft capsules of Production Examples 9-12 is effective for improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting platelet aggregation or maintaining platelet aggregation ability, and improving or maintaining blood flow, and is an oral composition. is useful as
［製造例１３－１６］（ＰＥＴ飲料の製造）
表８の配合にて、松樹皮とＤＨＡ、若しくは、松樹皮及び、ＧＡＢＡ、並びにＥＰＡ、コラーゲン及びエラスチンから選ばれる少なくとも１種を含有するＰＥＴ飲料を製造した。ＰＥＴ飲料は１本５００ｍｌで製造した。１日あたり１本摂取すればよい。また、製造例１３－１６のいずれのＰＥＴ飲料も、血管柔軟性改善又は維持、血管内皮機能改善又は維持、血小板凝集抑制又は血小板凝集能維持、及び血流改善又は維持に有効であり、経口組成物として有用である。
[Production Example 13-16] (Production of PET beverage)
PET beverages containing at least one selected from pine bark and DHA, or pine bark and GABA, EPA, collagen and elastin were produced according to the formulations shown in Table 8. PET beverages were produced in 500 ml bottles. One should be taken per day. In addition, any of the PET beverages of Production Examples 13-16 are effective in improving or maintaining vascular flexibility, improving or maintaining vascular endothelial function, inhibiting platelet aggregation or maintaining platelet aggregation ability, and improving or maintaining blood flow. It is useful as a product.
本発明の組成物は、血管の機能、血液の性状、血流等の改善又は維持を可能とし、健康食品等として用いることができることから、産業上有用である。 INDUSTRIAL APPLICABILITY The composition of the present invention is industrially useful because it can improve or maintain blood vessel function, blood properties, blood flow, etc., and can be used as health foods and the like.
Claims (6)
（１）松樹皮抽出物と人参とγ－アミノ酪酸と魚類由来のコラーゲンペプチドと魚類由来のエラスチンとを含有する組成物
（２）松樹皮抽出物と黒胡椒抽出物とγ－アミノ酪酸と魚類由来のコラーゲンペプチドと魚類由来のエラスチンとを含む組成物 A composition comprising a hot water extract of pine bark of French maritime pine as an active ingredient for suppressing, maintaining or improving vascular flexibility, and further comprising γ-aminobutyric acid, fish-derived collagen peptide and fish-derived elastin. and is in the form of granules , tablets, or capsules . (except for the composition of
(1) Composition containing pine bark extract, carrot, γ-aminobutyric acid, fish-derived collagen peptide, and fish-derived elastin
(2) A composition containing a pine bark extract, a black pepper extract, γ-aminobutyric acid, a fish-derived collagen peptide, and a fish-derived elastin
（１）松樹皮抽出物と人参とγ－アミノ酪酸と魚類由来のコラーゲンペプチドと魚類由来のエラスチンとを含有する組成物
（２）松樹皮抽出物と黒胡椒抽出物とγ－アミノ酪酸と魚類由来のコラーゲンペプチドと魚類由来のエラスチンとを含む組成物 A composition comprising a hot water extract of French maritime pine bark as an active ingredient for inhibiting platelet aggregation, further comprising γ-aminobutyric acid, fish-derived collagen peptide and fish-derived elastin , in granular form An oral composition for inhibiting platelet aggregation for humans, which is in the form of , tablet, or capsule (excluding compositions (1) and (2) below) .
(1) Composition containing pine bark extract, carrot, γ-aminobutyric acid, fish-derived collagen peptide, and fish-derived elastin
(2) A composition containing a pine bark extract, a black pepper extract, γ-aminobutyric acid, a fish-derived collagen peptide, and a fish-derived elastin
（１）松樹皮抽出物と人参とγ－アミノ酪酸と魚類由来のコラーゲンペプチドと魚類由来のエラスチンとを含有する組成物
（２）松樹皮抽出物と黒胡椒抽出物とγ－アミノ酪酸と魚類由来のコラーゲンペプチドと魚類由来のエラスチンとを含む組成物 A composition comprising a hot water extract of pine bark of French maritime pine as an active ingredient for improving or maintaining blood flow, further comprising γ-aminobutyric acid, fish-derived collagen peptide and fish-derived elastin, and granules 1. An oral composition for improving or maintaining blood flow for humans, which is in the form of a tablet, tablet, or capsule (excluding the following compositions (1) and (2)) .
(1) Composition containing pine bark extract, carrot, γ-aminobutyric acid, fish-derived collagen peptide, and fish-derived elastin
(2) A composition containing a pine bark extract, a black pepper extract, γ-aminobutyric acid, a fish-derived collagen peptide, and a fish-derived elastin
（１）松樹皮抽出物と人参とγ－アミノ酪酸と魚類由来のコラーゲンペプチドと魚類由来のエラスチン
（２）松樹皮抽出物と黒胡椒抽出物とγ－アミノ酪酸と魚類由来のコラーゲンペプチドと魚類由来のエラスチン For human beings, characterized in that a hot water extract of pine bark of French maritime pine, γ-aminobutyric acid, fish-derived collagen peptide and fish-derived elastin are blended and made into granules, tablets, or capsules. A method for producing an oral composition for suppressing, maintaining, or improving vascular flexibility (excluding a method of blending a combination of the following components (1) and (2)) .
(1) Pine bark extract, carrot, γ-aminobutyric acid, fish-derived collagen peptide, and fish-derived elastin
(2) Pine bark extract, black pepper extract, γ-aminobutyric acid, fish-derived collagen peptide, and fish-derived elastin
（１）松樹皮抽出物と人参とγ－アミノ酪酸と魚類由来のコラーゲンペプチドと魚類由来のエラスチン
（２）松樹皮抽出物と黒胡椒抽出物とγ－アミノ酪酸と魚類由来のコラーゲンペプチドと魚類由来のエラスチン For human beings, characterized in that a hot water extract of pine bark of French maritime pine, γ-aminobutyric acid, fish-derived collagen peptide and fish-derived elastin are blended and made into granules, tablets, or capsules. A method for producing an oral composition for inhibiting platelet aggregation (excluding a method of blending a combination of components (1) and (2) below) .
(1) Pine bark extract, carrot, γ-aminobutyric acid, fish-derived collagen peptide, and fish-derived elastin
(2) Pine bark extract, black pepper extract, γ-aminobutyric acid, fish-derived collagen peptide, and fish-derived elastin
（１）松樹皮抽出物と人参とγ－アミノ酪酸と魚類由来のコラーゲンペプチドと魚類由来のエラスチン
（２）松樹皮抽出物と黒胡椒抽出物とγ－アミノ酪酸と魚類由来のコラーゲンペプチドと魚類由来のエラスチン
For human beings, characterized in that a hot water extract of pine bark of French maritime pine, γ-aminobutyric acid, fish-derived collagen peptide and fish-derived elastin are blended and made into granules, tablets, or capsules. A method for producing an oral composition for improving or maintaining blood flow (excluding a method of blending a combination of components (1) and (2) below) .
(1) Pine bark extract, carrot, γ-aminobutyric acid, fish-derived collagen peptide, and fish-derived elastin
(2) Pine bark extract, black pepper extract, γ-aminobutyric acid, fish-derived collagen peptide, and fish-derived elastin
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| JP2006022082A (en) | 2003-11-17 | 2006-01-26 | Toyo Shinyaku:Kk | Lipid metabolism improver |
| JP2006028074A (en) | 2004-07-15 | 2006-02-02 | Shield Lab:Kk | Blood platelet coagulation inhibitory composition |
| JP2007306872A (en) | 2006-05-19 | 2007-11-29 | Suntory Ltd | Proanthocyanidin-containing tea beverage |
| JP2009120565A (en) | 2007-11-16 | 2009-06-04 | Nitto Best Kk | Prostacyclin(pgi2) production enhancer |
| JP2011093872A (en) | 2009-11-03 | 2011-05-12 | Kyushu Institute Of Technology | Platelet aggregation inhibitor containing water-soluble elastin derived from fish as active ingredient |
| JP2011225495A (en) | 2010-04-22 | 2011-11-10 | Hayashikane Sangyo Kk | Vascular endothelial cell protecting agent, and pharmaceutical composition, food and feed containing the same |
| JP2012229173A (en) | 2011-04-26 | 2012-11-22 | Ogawa & Co Ltd | Vascular endothelial function ameliorating agent |
| JP2015042688A (en) | 2008-10-10 | 2015-03-05 | 林兼産業株式会社 | Blood vessel improving agent |
| JP2018030826A (en) | 2016-08-26 | 2018-03-01 | 三和酒類株式会社 | Agent having gaba as active ingredient for maintaining or increasing content of fibrous-structure protein in biological tissue |
| JP2020164495A (en) | 2019-03-29 | 2020-10-08 | 株式会社東洋新薬 | Composition for male vitality and composition |
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- 2022-02-08 JP JP2022018236A patent/JP7106181B1/en active Active
- 2022-07-05 JP JP2022108676A patent/JP2023051730A/en active Pending
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| JP2006022082A (en) | 2003-11-17 | 2006-01-26 | Toyo Shinyaku:Kk | Lipid metabolism improver |
| JP2006028074A (en) | 2004-07-15 | 2006-02-02 | Shield Lab:Kk | Blood platelet coagulation inhibitory composition |
| JP2007306872A (en) | 2006-05-19 | 2007-11-29 | Suntory Ltd | Proanthocyanidin-containing tea beverage |
| JP2009120565A (en) | 2007-11-16 | 2009-06-04 | Nitto Best Kk | Prostacyclin(pgi2) production enhancer |
| JP2015042688A (en) | 2008-10-10 | 2015-03-05 | 林兼産業株式会社 | Blood vessel improving agent |
| JP2011093872A (en) | 2009-11-03 | 2011-05-12 | Kyushu Institute Of Technology | Platelet aggregation inhibitor containing water-soluble elastin derived from fish as active ingredient |
| JP2011225495A (en) | 2010-04-22 | 2011-11-10 | Hayashikane Sangyo Kk | Vascular endothelial cell protecting agent, and pharmaceutical composition, food and feed containing the same |
| JP2012229173A (en) | 2011-04-26 | 2012-11-22 | Ogawa & Co Ltd | Vascular endothelial function ameliorating agent |
| JP2018030826A (en) | 2016-08-26 | 2018-03-01 | 三和酒類株式会社 | Agent having gaba as active ingredient for maintaining or increasing content of fibrous-structure protein in biological tissue |
| JP2020164495A (en) | 2019-03-29 | 2020-10-08 | 株式会社東洋新薬 | Composition for male vitality and composition |
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| JP2023051677A (en) | 2023-04-11 |
| JP2023051730A (en) | 2023-04-11 |
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