JP2017171638A - Bone strength improver - Google Patents
Bone strength improver Download PDFInfo
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- JP2017171638A JP2017171638A JP2016062532A JP2016062532A JP2017171638A JP 2017171638 A JP2017171638 A JP 2017171638A JP 2016062532 A JP2016062532 A JP 2016062532A JP 2016062532 A JP2016062532 A JP 2016062532A JP 2017171638 A JP2017171638 A JP 2017171638A
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Abstract
Description
本発明は、骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、終末糖化産物生成阻害剤、ペントシジン生成阻害剤、及びカルボキシメチルリジン生成阻害剤に関する。 The present invention relates to a bone strength improving agent, a bone quality improving agent, a skin aging prevention or improving agent, a Maillard reaction inhibitor, a terminal glycation product production inhibitor, a pentosidine production inhibitor, and a carboxymethyllysine production inhibitor.
生体中のタンパク質は、グルコースなどの還元糖と非酵素的に反応すると、糖化産物として褐色色素が生成する。この反応はメイラード反応と称されている。
メイラード反応の初期反応では、タンパク質中のアミノ基と還元糖のアルデヒドがシッフ塩基を形成した後、アマドリ転位によりアマドリ化合物が生成される。その後の後期反応では、アマドリ化合物の脱水反応、加水分解反応、開裂反応、縮合反応など、二次的な長時間の複合的な反応を経て、終末糖化産物（advanced glycation end-products、以下「AGEs」ともいう）が生成される。
When proteins in a living body react non-enzymatically with a reducing sugar such as glucose, a brown pigment is produced as a saccharification product. This reaction is called the Maillard reaction.
In the initial reaction of the Maillard reaction, an amino group in a protein and an aldehyde of a reducing sugar form a Schiff base, and then an Amadori compound is generated by Amadori rearrangement. In the later reaction, the advanced glycation end-products (hereinafter referred to as “AGEs”) are subjected to secondary long-term complex reactions such as dehydration, hydrolysis, cleavage, and condensation of Amadori compounds. Is also generated).
これまでの研究により、メイラード反応による生体内のタンパク質の糖化は様々な症状や疾患に関与し、老化現象へとつながることが明らかとなっている。
例えば、メイラード反応により生成したAGEsの体内への蓄積は、糖尿病合併症、動脈硬化、骨粗鬆症、後縦靭帯骨化症、筋委縮、関節リウマチ、加齢黄斑変性、非アルコール性脂肪肝炎、インスリン抵抗性、歯周病、アルツハイマー病、神経変性疾患、皮膚疾患などのさまざまな疾患の発症の原因の１つとなり得る。
また、皮膚の真皮を構成するコラーゲンがメイラード反応により糖化されると、皮膚の弾力や張りを保っているコラーゲンが分解される。これにより皮膚は弾力を失い、張りの低下やシワやたるみの形成に関与する。
さらに、骨組織を構成するコラーゲンがメイラード反応により糖化されると、骨のしなやかさが失われる。骨のしなやかさが失われると、骨密度が正常であっても骨強度が低下する。したがって、生体内のコラーゲンに対するメイラード反応は、骨強度を示す指標の１つである骨のしなやかさ（骨質）の劣化にも影響する。
Previous studies have shown that glycation of proteins in the body by Maillard reaction is involved in various symptoms and diseases, leading to aging.
For example, accumulation of AGEs generated by Maillard reaction in the body is diabetic complications, arteriosclerosis, osteoporosis, posterior longitudinal ligament ossification, muscle atrophy, rheumatoid arthritis, age-related macular degeneration, nonalcoholic steatohepatitis, insulin resistance It can be one of the causes of various diseases such as sex, periodontal disease, Alzheimer's disease, neurodegenerative disease, and skin disease.
Further, when the collagen constituting the dermis of the skin is saccharified by the Maillard reaction, the collagen maintaining the elasticity and tension of the skin is decomposed. As a result, the skin loses its elasticity and is involved in the reduction of tension and the formation of wrinkles and sagging.
Furthermore, when the collagen constituting the bone tissue is saccharified by the Maillard reaction, the flexibility of the bone is lost. If the suppleness of the bone is lost, the bone strength decreases even if the bone density is normal. Therefore, the Maillard reaction with respect to collagen in the living body also affects the deterioration of bone flexibility (bone quality), which is one of the indexes indicating bone strength.
したがって、生体内でのメイラード反応の抑制は、老化現象へとつながる症状や疾患の予防又は改善につながる。そのため、メイラード反応抑制剤の探索、開発も盛んに行われている。例えば、ドクダミ（Houttuynia cordata）などの植物の抽出物が、メイラード反応阻害作用を有することが知られている（非特許文献１参照）。
しかしながら、カカオ（Theobroma cacao）抽出物とメイラード反応との関係については知られていなかった。
Therefore, suppression of the Maillard reaction in vivo leads to the prevention or improvement of symptoms and diseases that lead to the aging phenomenon. Therefore, search and development of Maillard reaction inhibitors are also actively performed. For example, it is known that an extract from a plant such as Houttuynia cordata has a Maillard reaction inhibitory action (see Non-Patent Document 1).
However, the relationship between cacao ( Theobroma cacao ) extract and Maillard reaction was not known.
本発明は、タンパク質のメイラード反応を抑制し、ペントシジン、カルボキシメチルリジン（以下、単に「CML」ともいう）などのAGEsの生成を抑制する作用を有する、メイラード反応抑制剤の提供を課題とする。
また本発明は、AGEs生成阻害作用を有する、AGEs生成阻害剤の提供を課題とする。
また本発明は、ペントシジン生成阻害作用を有する、ペントシジン生成阻害剤の提供を課題とする。
また本発明は、CML生成阻害作用を有する、CML生成阻害剤の提供を課題とする。
さらに本発明は、前記メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、及びCML生成阻害剤の効能を生かした、その投与の手段としての骨強度改善剤、骨質改善剤、並びに皮膚老化予防若しくは改善剤の提供を課題とする。
An object of the present invention is to provide a Maillard reaction inhibitor having an action of suppressing Maillard reaction of protein and suppressing generation of AGEs such as pentosidine and carboxymethyllysine (hereinafter also simply referred to as “CML”).
Another object of the present invention is to provide an AGEs production inhibitor having an AGEs production inhibitory action.
Another object of the present invention is to provide a pentosidine production inhibitor having a pentosidine production inhibitory action.
Another object of the present invention is to provide a CML production inhibitor having a CML production inhibitory action.
Furthermore, the present invention provides a bone strength improving agent, bone quality improving agent, and skin aging as a means of administration utilizing the effects of the Maillard reaction inhibitor, AGEs generation inhibitor, pentosidine generation inhibitor, and CML generation inhibitor. The issue is to provide preventive or ameliorating agents.
本発明者らは上記課題に鑑み、タンパク質のメイラード反応を抑制する作用を有する新たな素材について鋭意検討を行った。その結果、カカオ抽出物が、タンパク質（コラーゲン）のメイラード反応を抑制し、ペントシジン、CMLなどのAGEsの生成を阻害する作用を有することを見い出した。
本発明はこの知見に基づいて完成されたものである。
In view of the above-mentioned problems, the present inventors diligently studied a new material having an action of suppressing a protein Maillard reaction. As a result, it was found that the cacao extract has the action of suppressing the Maillard reaction of protein (collagen) and inhibiting the generation of AGEs such as pentosidine and CML.
The present invention has been completed based on this finding.
本発明は、カカオ抽出物を有効成分とする、骨強度改善剤に関する。
また本発明は、カカオ抽出物を有効成分とする、骨質改善剤に関する。
また本発明は、カカオ抽出物を有効成分とする、皮膚老化予防又は改善剤に関する。
また本発明は、カカオ抽出物を有効成分とする、メイラード反応抑制剤に関する。
また本発明は、カカオ抽出物を有効成分とする、AGEs生成阻害に関する。
また本発明は、カカオ抽出物を有効成分とする、ペントシジン生成阻害剤に関する。
さらに本発明は、カカオ抽出物を有効成分とする、CML生成阻害剤に関する。
The present invention relates to a bone strength improving agent comprising a cacao extract as an active ingredient.
The present invention also relates to a bone quality improving agent comprising a cacao extract as an active ingredient.
Moreover, this invention relates to the skin aging prevention or improvement agent which uses a cacao extract as an active ingredient.
The present invention also relates to a Maillard reaction inhibitor containing a cacao extract as an active ingredient.
Moreover, this invention relates to AGE production | generation inhibition which uses cacao extract as an active ingredient.
The present invention also relates to a pentosidine production inhibitor containing a cacao extract as an active ingredient.
Furthermore, this invention relates to the CML production | generation inhibitor which uses a cocoa extract as an active ingredient.
本発明のメイラード反応抑制剤は、タンパク質のメイラード反応を抑制し、ペントシジン、CMLなどのAGEsの生成を阻害する作用を有する。
また本発明のメイラード反応抑制剤で有効成分とするカカオ抽出物は、長期間摂取しても安全性が高く、骨強度改善効果、骨質改善効果、皮膚老化予防又は改善剤等を発揮し得る医薬品、医薬部外品、化粧料及び食品として、あるいはこれらへ配合するための素材又は製剤として有用である。
The Maillard reaction inhibitor of this invention has the effect | action which suppresses the Maillard reaction of protein and inhibits the production | generation of AGEs, such as pentosidine and CML.
In addition, the cacao extract as an active ingredient in the Maillard reaction inhibitor of the present invention is highly safe even if ingested for a long time, and can exhibit a bone strength improving effect, a bone quality improving effect, a skin aging preventing or improving agent, etc. They are useful as quasi-drugs, cosmetics and foods, or as materials or preparations for blending them.
本明細書において「予防」とは、個体における疾患若しくは症状の発症の防止若しくは遅延、又は個体の疾患若しくは症状の発症の危険性を低下させることをいう。
また、本明細書において「改善」とは、疾患、症状若しくは状態の好転若しくは緩和、疾患、症状若しくは状態の悪化の防止若しくは遅延、又は疾患、症状若しくは状態の進行の逆転、防止若しくは遅延をいう。
さらに本明細書において「非治療的」とは、医療行為、すなわち治療による人体への処置行為を含まないことを意味する。
As used herein, “prevention” refers to preventing or delaying the onset of a disease or symptom in an individual, or reducing the risk of developing an individual's disease or symptom.
In the present specification, “improvement” means improvement or alleviation of a disease, symptom or condition, prevention or delay of deterioration of the disease, symptom or condition, or reversal, prevention or delay of progression of the disease, symptom or condition. .
Further, in the present specification, “non-therapeutic” means that it does not include medical treatment, that is, treatment treatment to the human body by treatment.
「メイラード反応」とは、タンパク質と還元糖とが非酵素的に反応して、一般にAGEsと称される糖化産物を生成する反応をいう。メイラード反応は一般に、シッフ塩基の形成を経てタンパク質からアマドリ化合物が生成される初期反応と、アマドリ化合物からAGEsが生成される後期反応とに分けられる。本明細書における「メイラード反応」はこれらのうち、後期反応（以下、「後期のメイラード反応」ともいう）を好ましく指す。
また本明細書において「メイラード反応」は、コラーゲンに対するメイラード反応を好ましく指す。生体内に存在するコラーゲンとしては、皮膚の真皮を構成するコラーゲンや、骨組織を構成するコラーゲンが挙げられる。
“Maillard reaction” refers to a reaction in which a protein and a reducing sugar react non-enzymatically to produce a glycation product generally called AGEs. The Maillard reaction is generally divided into an initial reaction in which an Amadori compound is generated from a protein through the formation of a Schiff base and a late reaction in which AGEs are generated from an Amadori compound. Among these, the “Maillard reaction” in this specification preferably refers to a late reaction (hereinafter also referred to as “late Maillard reaction”).
Further, in the present specification, “Maillard reaction” preferably refers to Maillard reaction on collagen. Examples of collagen present in the living body include collagen constituting the dermis of skin and collagen constituting bone tissue.
メイラード反応によって生成する「AGEs」は、単一の物質を指すものではなく、各種糖化産物の総称である。タンパク質、特に骨コラーゲン、から生成するAGEsとしては、ペントシジン、CML、ピラリン、クロスリン、ピロピリジン、などが挙げられる。 “AGEs” produced by the Maillard reaction do not refer to a single substance, but are a general term for various saccharification products. Examples of AGEs generated from proteins, particularly bone collagen, include pentosidine, CML, pyralin, croslin, and pyropyridine.
適度な弾力を備え、骨質を正常に保つには、骨コラーゲン分子を正しく整然と架橋させる必要がある。骨コラーゲン分子が正しく整然と架橋されない場合、コラーゲン分子が無秩序につなぎとめられてしまうので、骨はしなやかさが欠け、固くて脆く、弾力性が低下する。
また、骨の強度（骨強度）を決定する要因としては、骨密度の他に、骨質も挙げられる。十分な骨密度を有していたとしても、骨コラーゲン分子が正しく架橋されず弾力性が低下し、骨質が劣化している場合には、骨強度は低下する。
In order to maintain an appropriate elasticity and keep the bone quality normal, it is necessary to cross-link bone collagen molecules correctly and orderly. If the bone collagen molecules are not properly and orderly crosslinked, the collagen molecules will be segregated together, so that the bone lacks flexibility, is hard and brittle, and loses elasticity.
In addition to bone density, factors that determine bone strength (bone strength) include bone quality. Even if the bone density is sufficient, if the bone collagen molecules are not properly cross-linked and the elasticity is lowered and the bone quality is deteriorated, the bone strength is lowered.
ここで、骨コラーゲンに対するメイラード反応が、骨質及び骨強度に関与することについて、具体例を挙げて詳細に説明する。
骨粗鬆症は、骨強度が低下して骨折リスクが高まる疾患で、現在、日本の骨粗鬆症の患者は1260万人と推測されている。骨粗鬆症に伴う骨折は、いわゆる「寝たきり」を生み出す原因となることや、死亡のリスクを高めることが明らかにされている。骨強度には骨密度と骨質が関与すると2000年にNIH consensus statementで定義され、骨密度だけでなく骨質ケアの重要性が指摘されている。
骨質は、骨代謝状態、骨の微細構造や骨を構成するコラーゲンの架橋状態によって決定され、特にコラーゲンの架橋構造が、骨の強度に重要な役割を担い、骨質を規定する因子であると考えられている。コラーゲン架橋には大きく分けて、生理的架橋（善玉架橋）と非生理的架橋（悪玉架橋）がある（前田和洋、骨粗鬆症治療7：3、2008）。生理的架橋は、生体内の酵素（lysyl oxidase）により形成される架橋であるのに対し、非生理的架橋は、終末糖化産物（Advanced glycation end products：AGEs）が非酵素的な反応により形成されることで生じる。この非生理的架橋は骨の構造的な脆弱化をもたらし、さらにこれが増加し、生理的架橋が減少することで骨質が劣化し、骨強度が低下する（前田和洋、骨粗鬆症治療7：4、2008）。
加齢や酸化ストレスの増大、糖化の亢進により、AGEsが骨コラーゲンに蓄積しコラーゲンを変性させることが、骨粗鬆症骨折に繋がることが明らかになっている（Saito M.，Osteoporos Int.，2006，vol．17，p．986-995,）。このようなことから、AGEsの生成を抑制することでコラーゲンの非生理的架橋形成を防ぎ、骨折リスクを高める骨質低下を予防できさらには骨強度の低下を予防できると考えた。
Here, a specific example will be used to explain in detail that the Maillard reaction to bone collagen is involved in bone quality and bone strength.
Osteoporosis is a disease in which bone strength decreases and fracture risk increases, and it is estimated that there are currently 12.6 million osteoporosis patients in Japan. Fractures associated with osteoporosis have been shown to cause so-called “bedridden” and increase the risk of death. Bone strength was defined by the NIH consensus statement in 2000 that bone density and bone quality are involved, and the importance of bone quality care as well as bone density is pointed out.
Bone quality is determined by bone metabolic status, bone microstructure, and the cross-linked state of collagen that constitutes bone. Collagen cross-linked structure plays an important role in bone strength and is considered to be a factor that defines bone quality. It has been. Collagen cross-linking can be broadly divided into physiological cross-linking (good cross-linking) and non-physiological cross-linking (bad cross-linking) (Maeda Kazuhiro, Osteoporosis Treatment 7: 3, 2008). Physiological cross-links are cross-links formed by lysyl oxidase in vivo, whereas non-physiological cross-links are formed by advanced glycation end products (AGEs) by non-enzymatic reactions. Caused by This non-physiological cross-linking leads to structural weakening of the bone, which further increases and decreases the cross-linkage, which degrades bone quality and decreases bone strength (Maeda Kazuhiro, Osteoporosis Treatment 7: 4, 2008) ).
It has been clarified that AGEs accumulate in bone collagen and denature collagen due to aging, increased oxidative stress and increased glycation, leading to osteoporotic fractures (Saito M., Osteoporos Int., 2006, vol. 17, p. 986-995,). Therefore, it was considered that by suppressing the generation of AGEs, the formation of non-physiological crosslinks of collagen can be prevented, and bone deterioration that can increase the risk of fracture can be prevented, and further, the decrease in bone strength can be prevented.
本発明において「皮膚老化」とは、加齢に伴う生理的な皮膚老化や、紫外線照射などの外部刺激による皮膚老化を指す。具体的には、「皮膚老化」とは、皮膚の張りや弾力性が低下し、シワやたるみが生じることを意味する。
前述したように、皮膚のコラーゲンがメイラード反応により糖化されると、コラーゲンが分解され、皮膚の老化が引き起こされる。
In the present invention, “skin aging” refers to physiological skin aging associated with aging and skin aging caused by external stimuli such as ultraviolet irradiation. Specifically, “skin aging” means that skin tension and elasticity are reduced, and wrinkles and sagging occur.
As described above, when the collagen in the skin is saccharified by the Maillard reaction, the collagen is decomposed to cause aging of the skin.
本発明の骨強度改善剤、骨質改善剤、皮膚老化予防又は改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、及びCML生成阻害剤はそれぞれ、カカオ抽出物を有効成分とする。
なお、本発明で用いるカカオは、アオギリ（Sterculiaceae）科カカオ（Theobroma）属の常緑高木である。
The bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, and CML production inhibitor of the present invention each have a cacao extract as an active ingredient. .
The cacao used in the present invention is an evergreen tree belonging to the genus Theobroma in the Sterculiaceae family.
本発明で有効成分として用いるカカオ抽出物の製造には、カカオの任意の部分が使用可能である。例えば、根、塊根、根茎、幹、枝、茎、葉（葉身、葉柄等）、樹皮、樹液、樹脂、花（花弁、子房等）、果実（成熟果実、未熟果実等）、果皮、種子等を用いることができる。また、これらの部位を複数組み合わせて用いてもよい。
なかでも、本発明に用いるカカオ抽出物は、カカオの種子の抽出物であることが好ましい。
なお、本発明で用いるカカオは天然成分由来であり、一般食用に用いられているため安全性も高い。よってカカオ抽出物は安全性が高い。
Any part of cocoa can be used for producing the cocoa extract used as an active ingredient in the present invention. For example, root, tuberous root, rhizome, stem, branch, stem, leaf (leaf blade, petiole etc.), bark, sap, resin, flower (petal, ovary etc.), fruit (mature fruit, immature fruit etc.), peel, Seeds and the like can be used. A combination of these parts may also be used.
Especially, it is preferable that the cocoa extract used for this invention is an extract of a cocoa seed.
In addition, the cacao used in the present invention is derived from natural ingredients, and since it is used for general food, it has high safety. Therefore, cocoa extract is highly safe.
本発明に用いるカカオ抽出物は、植物の抽出に用いられる通常の抽出方法により得ることができる。抽出方法は適宜設定することができ、上記植物を常温又は加温下にて抽出するか又はソックスレー抽出器等の抽出器具を用いて抽出することにより得ることが好ましい。
抽出物の調製には、カカオをそのまま又は乾燥粉砕して用いることができる。また、植物の水蒸気蒸留物又は圧搾物を用いることもでき、これらは精油等より精製したものを用いることもでき、また市販品を利用することもできる。カカオ、又はその水蒸気蒸留物若しくは圧搾物は、いずれかを単独で、又は２種以上を組み合わせて使用してもよい。
The cocoa extract used in the present invention can be obtained by a usual extraction method used for plant extraction. The extraction method can be appropriately set, and is preferably obtained by extracting the plant at room temperature or under heating or using an extraction tool such as a Soxhlet extractor.
For the preparation of the extract, cocoa can be used as it is or after dry pulverization. Moreover, the water vapor | steam distillate or press thing of a plant can also be used, These can also use what refine | purified from essential oil etc., and can also use a commercial item. You may use cacao, its steam distillate, or a pressing thing individually or in combination of 2 or more types.
カカオの抽出物の調製に用いる抽出溶媒は、植物成分の抽出に通常用いられるものより適宜選択することができる。例えば水；メタノール、エタノール、プロパノール、ブタノール等のアルコール類；エチレングリコール、プロピレングリコール、1,2-ブチレングリコール、1,3-ブチレングリコール、1,4-ブチレングリコール、2,3-ブチレングリコール等の多価アルコール類；アセトン、メチルエチルケトン等のケトン類；酢酸メチル、酢酸エチル等のエステル類；テトラヒドロフラン、ジエチルエーテル等の鎖状又は環状エーテル類；ポリエチレングリコール等のポリエーテル類；ジクロロメタン、ジクロロエタン、クロロホルム、四塩化炭素等のハロゲン化炭化水素類；ヘキサン、シクロヘキサン、石油エーテル等の炭化水素類；ベンゼン、トルエン等の芳香族炭化水素類；ピリジン類；超臨界二酸化炭素；油脂、ワックス、その他オイル等が挙げられる。これらは単独で用いてもよいし、２種以上を組み合わせて用いてもよい。なかでも、水、アルコール類、又はこれらの混合溶媒が好ましく、アルコール水溶液がより好ましく、エタノール水溶液がさらに好ましい。また、抽出に際して酸やアルカリなどを添加し、抽出溶媒のｐＨを調整してもよい。 The extraction solvent used for the preparation of the cocoa extract can be appropriately selected from those usually used for the extraction of plant components. For example, water; alcohols such as methanol, ethanol, propanol, butanol; ethylene glycol, propylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, 2,3-butylene glycol, etc. Polyhydric alcohols; Ketones such as acetone and methyl ethyl ketone; Esters such as methyl acetate and ethyl acetate; Linear or cyclic ethers such as tetrahydrofuran and diethyl ether; Polyethers such as polyethylene glycol; Dichloromethane, dichloroethane, chloroform, Halogenated hydrocarbons such as carbon tetrachloride; Hydrocarbons such as hexane, cyclohexane and petroleum ether; Aromatic hydrocarbons such as benzene and toluene; Pyridines; Supercritical carbon dioxide; Oils, waxes and other oils Can be mentioned. These may be used alone or in combination of two or more. Especially, water, alcohol, or these mixed solvents are preferable, alcohol aqueous solution is more preferable, and ethanol aqueous solution is further more preferable. Further, acid or alkali may be added during extraction to adjust the pH of the extraction solvent.
抽出条件も通常の条件を適用でき、例えば植物を０℃以上（好ましくは２０℃以上）１００℃以下（好ましくは８０℃以下、より好ましくは４０℃以下）で１分以上（好ましくは１時間以上、より好ましくは１日以上、さらに好ましくは７日以上）５０日以下（好ましくは３０日以下）浸漬又は加熱還流すればよい。抽出効率を上げる為、併せて攪拌を行ったり、溶媒中でホモジナイズ処理を行ってもよい。用いる抽出溶媒の量は、植物重量（乾燥物換算）に対して１倍量以上（好ましくは５倍量以上、より好ましくは８倍以上）１００倍量以下（好ましくは５０倍量以下、より好ましくは４０倍量以下）である。 Normal conditions can be applied as extraction conditions. For example, plants can be used at 0 ° C or higher (preferably 20 ° C or higher) and 100 ° C or lower (preferably 80 ° C or lower, more preferably 40 ° C or lower) for 1 minute or longer (preferably 1 hour or longer). More preferably, it may be immersed for 1 day or more, more preferably 7 days or more) and 50 days or less (preferably 30 days or less) or refluxing with heating. In order to increase the extraction efficiency, stirring may be performed together or homogenization treatment may be performed in a solvent. The amount of the extraction solvent to be used is 1-fold or more (preferably 5-fold or more, more preferably 8-fold or more) 100-fold or less (preferably 50-fold or less, more preferably) relative to the plant weight (in terms of dry matter). Is 40 times or less).
本発明において、抽出物をそのまま用いてもよいし、さらに適当な分離手段、例えばゲル濾過、クロマトグラフィー、精密蒸留等により活性の高い画分を分画して用いることもできる。また、得られた抽出物を希釈、濃縮又は凍結乾燥した後、粉末又はペースト状に調製して用いることもできる。また、前記方法により得られた抽出物を、前記抽出溶媒とは異なる溶媒で転溶して用いることもできる。
本発明において抽出物とは、前記のような抽出方法で得られた各種溶剤抽出液、その希釈液、その濃縮液、その精製画分、その乾燥末又はその転溶液を含むものである。
In the present invention, the extract may be used as it is, or a fraction having high activity can be fractionated and used by an appropriate separation means such as gel filtration, chromatography, precision distillation and the like. Moreover, after the obtained extract is diluted, concentrated or freeze-dried, it can be prepared into a powder or paste and used. In addition, the extract obtained by the above method can be used by being dissolved in a solvent different from the extraction solvent.
In the present invention, the extract includes various solvent extracts obtained by the extraction method as described above, diluted solutions thereof, concentrated solutions thereof, purified fractions thereof, dried powders thereof or transferred solutions thereof.
後述の実施例で実証するように、カカオ抽出物は、タンパク質（特にコラーゲン）のメイラード反応を抑制し、AGEsの生成を阻害する作用を有する。前述のとおり、生体内でのメイラード反応は、老化現象に関わっている。特に、コラーゲンに対するメイラード反応は、皮膚の老化や骨質の劣化に関与していることが知られている。よってカカオ抽出物は、メイラード反応を抑制することが有用と考えられる各種症状の予防、改善又は治療に有効であると考えられる。
例えば、コラーゲン由来のAGEsの生成阻害作用を有するカカオ抽出物は、骨強度改善、及び骨質改善、皮膚老化予防若しくは改善剤等に広く有効であると考えられる。よって、カカオ抽出物のAGEsの生成阻害作用を生かし、カカオ抽出物を、骨強度改善剤、骨質改善剤、又は皮膚老化予防若しくは改善剤の有効成分とすることができる。
As demonstrated in the examples described later, the cocoa extract has an action of suppressing the Maillard reaction of proteins (particularly collagen) and inhibiting the generation of AGEs. As described above, the Maillard reaction in vivo is related to the aging phenomenon. In particular, the Maillard reaction to collagen is known to be involved in skin aging and bone quality deterioration. Therefore, the cacao extract is considered to be effective for the prevention, amelioration, or treatment of various symptoms that are thought to be useful to suppress the Maillard reaction.
For example, a cacao extract having an inhibitory action on the production of collagen-derived AGEs is considered to be widely effective for improving bone strength, improving bone quality, preventing or improving skin aging, and the like. Therefore, taking advantage of the AGE generation inhibitory action of the cocoa extract, the cocoa extract can be used as an active ingredient of a bone strength improving agent, a bone quality improving agent, or a skin aging prevention or improving agent.
前述の有効成分は、骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤として使用することができる。また、前述の有効成分を骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤の製造のために使用することができる。 The aforementioned active ingredient can be used as a bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, or CML production inhibitor. In addition, the above-mentioned active ingredients are used for the production of bone strength improvers, bone quality improvers, skin aging preventive or ameliorants, Maillard reaction inhibitors, AGEs production inhibitors, pentosidine production inhibitors, or CML production inhibitors. be able to.
本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、及びCML生成阻害剤の形態は適宜選択することができる。例えば、前記有効成分単体を本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤として用いてもよい。あるいは、前記有効成分と、薬学的に許容される担体とを含む、本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤を医薬組成物として使用してもよい。あるいは、本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤を化粧料組成物又は食品組成物に含有させてもよい。 The forms of the bone strength improving agent, bone quality improving agent, skin aging preventing or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, and CML production inhibitor of the present invention can be appropriately selected. For example, the active ingredient alone may be used as the bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs generation inhibitor, pentosidine generation inhibitor, or CML generation inhibitor of the present invention. Good. Alternatively, the bone strength improving agent, bone substance improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor of the present invention comprising the active ingredient and a pharmaceutically acceptable carrier. An agent or a CML production inhibitor may be used as a pharmaceutical composition. Alternatively, the bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, or CML production inhibitor of the present invention is a cosmetic composition or food composition. You may make it contain.
医薬組成物を調製する場合は、通常、前記有効成分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。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、植物性油などの溶媒又は分散媒体などが挙げられる。 When preparing a pharmaceutical composition, it is usually prepared as a preparation containing the 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 or encapsulating material that does not react with the active ingredient, such as water. , Ethanol, polyols, suitable mixtures thereof, solvents or dispersion media such as vegetable oils, and the like.
医薬組成物は、経口により、非経口により、例えば、口腔内に、皮膚に、粘膜に、又は鼻腔内に投与される。経口投与製剤としては、錠剤、顆粒剤、細粒剤、散剤、カプセル剤、チュアブル剤、ペレット剤、シロップ剤、液剤、懸濁剤及び吸入剤などが挙げられる。非経口投与製剤としては、坐剤、保持型浣腸剤、点鼻剤、口腔洗浄剤、並びに軟膏、クリーム剤、ローション、ゲル剤、制御放出パッチ剤及び貼付剤などの皮膚外用剤などが挙げられる。 The pharmaceutical composition is administered orally, parenterally, for example, intraorally, dermally, mucosally, or intranasally. Examples of the preparation for oral administration include tablets, granules, fine granules, powders, capsules, chewables, pellets, syrups, solutions, suspensions and inhalants. Examples of parenteral preparations include suppositories, retention enemas, nasal drops, mouth washes, and external preparations for skin such as ointments, creams, lotions, gels, controlled-release patches and patches. .
医薬組成物はさらに医薬分野において慣用の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、矯味剤などがあり、必要に応じて使用できる。長時間作用できるように徐放化するためには、既知の遅延剤等でコーティングすることもできる。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。 The pharmaceutical composition may further contain additives conventionally used in the pharmaceutical field. Such additives include, for example, excipients, binders, disintegrants, lubricants, antioxidants, colorants, flavoring agents, and the like, and can be used as necessary. In order to achieve sustained release so that it can act for a long time, it can also be coated with a known retarder or the like. If necessary, other additives and drugs such as antacids and gastric mucosa protective agents may be added.
化粧料組成物を調製する場合、その形態は適宜選択することができ、溶液、乳液、粉末、水−油二層系、水−油−粉末三層系、ゲル、タブレット等の固形、エアゾール、ミスト、カプセル及びシート等任意の形態とすることができる。また、化粧料組成物の製品形態も任意であり、例えば、洗顔料、メーク落とし、化粧水、美容液、パック、乳液、クリーム及びサンスクリーン等のスキンケア化粧料、ファンデーション、化粧下地、口紅、アイシャドー、アイライナー、マスカラ、アイブロー、頬紅及びネイルエナメル等のメイクアップ化粧料、ヘアシャンプー、ヘアリンス、整髪料、染毛料及び育毛剤等の毛髪化粧料、石鹸、ボディソープ、デオドラント化粧料及び浴用剤等のボディ洗浄料、歯磨剤及び洗口剤等の口腔化粧料、香水等の芳香化粧料等が挙げられる。また、この化粧料は、日本の医薬品、医療機器等の品質、有効性及び安全性の確保等に関する法律上、化粧品及び医薬部外品のどちらに属しても良い。 When preparing a cosmetic composition, the form thereof can be selected as appropriate, such as solution, emulsion, powder, water-oil two-layer system, water-oil-powder three-layer system, gel, tablet and other solids, aerosol, It can be in any form such as mist, capsule, and sheet. In addition, the product form of the cosmetic composition is also arbitrary. For example, skin care cosmetics such as face wash, makeup remover, lotion, cosmetic liquid, pack, milky lotion, cream and sunscreen, foundation, makeup base, lipstick, eye Makeup cosmetics such as shadow, eyeliner, mascara, eyebrow, blusher and nail enamel, hair cosmetics such as hair shampoo, hair rinse, hair styling, hair dye and hair restorer, soap, body soap, deodorant cosmetic and bath preparation And other body cleansing agents, oral cosmetics such as dentifrices and mouthwashes, and aromatic cosmetics such as perfumes. In addition, this cosmetic may belong to either cosmetics or quasi-drugs in accordance with laws relating to ensuring the quality, effectiveness and safety of Japanese pharmaceuticals and medical devices.
化粧料組成物は、化粧品、医薬部外品及び医薬品等に慣用される他の成分、例えば、粉末成分、液体油脂、固体油脂、ロウ、炭化水素、高級脂肪酸、高級アルコール、エステル、シリコーン、アニオン界面活性剤、カチオン界面活性剤、両性界面活性剤、非イオン界面活性剤、保湿剤、水溶性高分子、増粘剤、皮膜剤、紫外線吸収剤、金属イオン封鎖剤、低級アルコール、多価アルコール、糖、アミノ酸、有機アミン、高分子エマルジョン、ｐＨ調整剤、皮膚栄養剤、ビタミン、酸化防止剤、酸化防止助剤、香料、水等を必要に応じて配合し、常法により製造することができる。
その他の化粧料組成物に配合可能な成分としては、例えば、防腐剤、消炎剤、美白剤、各種抽出物、賦活剤、血行促進剤、抗脂漏剤、抗炎症剤、及び殺菌剤等が挙げられる。
The cosmetic composition includes other components commonly used in cosmetics, quasi drugs and pharmaceuticals, such as powder components, liquid fats and oils, solid fats and oils, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, silicones, anions. Surfactant, cationic surfactant, amphoteric surfactant, nonionic surfactant, humectant, water-soluble polymer, thickener, film agent, UV absorber, sequestering agent, lower alcohol, polyhydric alcohol , Sugar, amino acids, organic amines, polymer emulsions, pH adjusters, skin nutrients, vitamins, antioxidants, antioxidant auxiliaries, fragrances, water, etc. may be blended as necessary and manufactured by conventional methods. it can.
Examples of components that can be blended in other cosmetic compositions include preservatives, anti-inflammatory agents, whitening agents, various extracts, activators, blood circulation promoters, antiseborrheic agents, anti-inflammatory agents, and bactericides. Can be mentioned.
前記医薬組成物及び化粧料組成物は、口腔用組成物、外用組成物、内服組成物などの形態で適用することができる。
また前記医薬組成物及び化粧料組成物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。
The pharmaceutical composition and the cosmetic composition can be applied in the form of an oral composition, an external composition, an internal use composition, and the like.
The pharmaceutical composition and cosmetic composition may be used therapeutically or non-therapeutically.
本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤は、食料、飲料、飼料、ペットフードに添加又はこれらと混合して使用することができる。あるいは、コラーゲンに対するメイラード反応の抑制により治療、予防又は改善しうる疾患又は状態の治療、予防又は改善等をコンセプトとしてその旨を表示した飲食品、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などに添加又は配合して使用することができる。前記の、健康食品、機能性表示食品、病者用食品、特定保健用食品は、具体的には、細粒剤、錠剤、顆粒剤、散剤、カプセル剤、シロップ剤、液剤、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、医薬製剤と同様に製造することができ、前記有効成分と、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。さらに、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、ダイエット飲料などの液状食品組成物、プリン、ヨーグルトなどの半固形食品組成物、麺類、菓子類、スプレッド類等に、本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤を添加又はこれらと混合して、食品組成物を製造することができる。 The bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, or CML production inhibitor of the present invention is used in foods, beverages, feeds, and pet foods. It can be added or mixed with these. Or a food or drink with the concept of treatment, prevention or improvement of a disease or condition that can be treated, prevented or ameliorated by suppressing the Maillard reaction to collagen, that is, health food, functionally labeled food, for the sick It can be used by adding or blending into foods and foods for specified health use. The above-mentioned health foods, functional indication foods, foods for sick people, foods for specified health use, specifically, fine granules, tablets, granules, powders, capsules, syrups, liquids, liquid foods, etc. It can be used as various preparation forms. A food in the form of a preparation can be produced in the same manner as a pharmaceutical preparation, and the active ingredient is mixed with a food-acceptable carrier, such as an appropriate excipient, and then produced using conventional means. Can do. Furthermore, soups, juices, fruit juice drinks, milk, milk drinks, whey drinks, lactic acid bacteria drinks, tea drinks, alcoholic drinks, coffee drinks, carbonated drinks, soft drinks, water drinks, cocoa drinks, jelly drinks, sports Bone strength improving agent, bone quality improving agent, skin aging preventing or improving agent of the present invention for liquid food compositions such as beverages and diet beverages, semi-solid food compositions such as pudding and yogurt, noodles, confectionery, spreads, etc. A food composition can be produced by adding or mixing a Maillard reaction inhibitor, an AGEs production inhibitor, a pentosidine production inhibitor, or a CML production inhibitor.
食品組成物には、種々の食品添加物、例えば、酸化防止剤、有機酸類、有機酸塩類、無機酸類、無機酸塩類、無機塩類、乳化剤、糖類、ビタミン類、色素、香料、調味料、甘味料、酸味料、果汁エキス類、野菜エキス類、花蜜エキス類、pH調整剤、品質安定剤、保存剤等、通常の食品又は飲料の原料として使用されている添加剤を単独あるいは併用して配合してもよい。 The food composition includes various food additives such as antioxidants, organic acids, organic acid salts, inorganic acids, inorganic acid salts, inorganic salts, emulsifiers, sugars, vitamins, dyes, flavors, seasonings, sweetness. Additives used as raw materials for ordinary foods or beverages, alone or in combination, such as foods, acidulants, fruit juices, vegetable extracts, nectar extracts, pH adjusters, quality stabilizers, preservatives, etc. May be.
本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤における前記有効成分の含有量は適宜決定できる。例えば、本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤の総量中、前記有効成分の含有量は乾燥物換算で0.1質量%以上が好ましく、1質量%以上がより好ましく、5質量％以上がさらに好ましい。また、その上限値は50質量%以下が好ましく、40質量%以下がより好ましく、20質量%以下がさらに好ましい。さらに、前記有効成分の含有量の数値範囲は、0.1〜50質量%が好ましく、1〜40質量%がより好ましく、5〜20質量%がさらに好ましい。 The content of the active ingredient in the bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, or CML production inhibitor of the present invention can be determined as appropriate. . For example, the active ingredient is contained in the total amount of the bone strength improving agent, bone quality improving agent, skin aging preventing or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, or CML production inhibitor of the present invention. The amount is preferably 0.1% by mass or more, more preferably 1% by mass or more, and further preferably 5% by mass or more in terms of dry matter. The upper limit is preferably 50% by mass or less, more preferably 40% by mass or less, and further preferably 20% by mass or less. Furthermore, the numerical range of the content of the active ingredient is preferably 0.1 to 50% by mass, more preferably 1 to 40% by mass, and further preferably 5 to 20% by mass.
本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤の投与又は摂取対象は、好ましくは温血脊椎動物であり、より好ましくは哺乳動物である。本明細書において哺乳動物は、例えば、ヒト、並びにサル、マウス、ラット、ウサギ、イヌ、ネコ、ウシ、ウマ、ブタなどの非ヒト哺乳動物が挙げられる。本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤は、ヒトへの投与に好適である。 The subject of administration or ingestion of the bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, or CML production inhibitor of the present invention is preferably warm blood It is a vertebrate, more preferably a mammal. As used herein, mammals include, for example, humans and non-human mammals such as monkeys, mice, rats, rabbits, dogs, cats, cows, horses, and pigs. The bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, or CML production inhibitor of the present invention is suitable for administration to humans.
本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、及びCML生成阻害剤は、骨強度改善効果、骨質改善効果、皮膚老化予防若しくは改善効果、メイラード反応抑制効果、AGEs生成阻害効果、ペントシジン生成阻害効果、又はCML生成阻害効果を所望する対象者に好ましく適用することができる。
また、本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、及びCML生成阻害剤は、コラーゲンに対するメイラード反応が亢進又は惹起されている条件下、又はコラーゲン由来のAGEsの生成が促進されている条件下で好ましく適用することができる。さらに、本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、及びCML生成阻害剤は、経口投与するのが好ましい。
Bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, and CML production inhibitor of the present invention are bone strength improvement effect, bone quality improvement effect, It can be preferably applied to a subject who wants skin aging prevention or improvement effect, Maillard reaction suppression effect, AGEs production inhibitory effect, pentosidine production inhibitory effect, or CML production inhibitory effect.
Further, the bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, and CML production inhibitor of the present invention have enhanced Maillard reaction to collagen or It can be preferably applied under conditions that are induced or under conditions where the generation of collagen-derived AGEs is promoted. Furthermore, the bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, and CML production inhibitor of the present invention are preferably administered orally.
本発明の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤をヒト又は非ヒト動物に投与又は摂取させることで、メイラード反応を抑制し、ペントシジン、CMLなどのAGEsの生成を抑制することができる。そして、コラーゲン由来のAGEsの生成を抑制することで、骨質が改善され、骨強度も改善される。また、コラーゲン由来のAGEsの生成を抑制することで、皮膚状態も改善され、皮膚の老化を予防又は改善できる。
本発明の剤を用いた、骨強度改善方法、骨質改善方法、皮膚老化予防若しくは改善方法、メイラード反応抑制方法、AGEs生成阻害方法、ペントシジン生成阻害方法、又はCML生成阻害方法において、投与又は摂取することで適用する前記有効成分量は、個体の状態、体重、性別、年齢、素材の活性、投与又は摂取経路、投与又は摂取スケジュール、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。例えば、前記有効成分の投与又は摂取量は、乾燥物換算で、100mg/kg体重/日以上が好ましく、500mg/kg体重/日以上がより好ましい。また、その上限値は、10,000mg/kg体重/日以下が好ましく、5,000mg/kg体重/日以下がより好ましい。さらに、前記有効成分の投与又は摂取量の数値範囲は、100〜10,000mg/kg体重/日が好ましく、500〜5,000mg/kg体重/日がより好ましい。
なお前記有効成分は、１日１回〜数回に分け、又は任意の期間及び間隔で摂取・投与され得る。また、前記有効成分の投与又は摂取は、全身への投与又は摂取でもよいし、局所への投与又は摂取でもよい。
Bone strength improving agent, bone quality improving agent, skin aging preventing or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, or CML production inhibitor of the present invention is administered or ingested to a human or non-human animal Thus, the Maillard reaction can be suppressed, and the generation of AGEs such as pentosidine and CML can be suppressed. And by suppressing the production of collagen-derived AGEs, bone quality is improved and bone strength is also improved. Moreover, by suppressing the production of collagen-derived AGEs, the skin condition is also improved, and skin aging can be prevented or improved.
Administration or ingestion in the bone strength improvement method, bone quality improvement method, skin aging prevention or improvement method, Maillard reaction suppression method, AGEs production inhibition method, pentosidine production inhibition method, or CML production inhibition method using the agent of the present invention The amount of the active ingredient to be applied can be appropriately determined according to the individual's condition, weight, sex, age, material activity, administration or intake route, administration or intake schedule, formulation form or other factors. For example, the administration or intake of the active ingredient is preferably 100 mg / kg body weight / day or more, more preferably 500 mg / kg body weight / day or more in terms of dry matter. The upper limit is preferably 10,000 mg / kg body weight / day or less, more preferably 5,000 mg / kg body weight / day or less. Further, the numerical range of administration or intake of the active ingredient is preferably 100 to 10,000 mg / kg body weight / day, and more preferably 500 to 5,000 mg / kg body weight / day.
The active ingredient can be taken or administered once a day to several times a day, or at an arbitrary period and interval. Moreover, administration or ingestion of the active ingredient may be systemic administration or ingestion, or local administration or ingestion.
上述した実施形態に関し、本発明はさらに下記の骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、CML生成阻害剤、並びに抽出物又はその使用方法とそれらを含む剤についてさらに詳細に説明する。 With respect to the above-described embodiments, the present invention further includes the following bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, CML production inhibitor, and extraction. The product or its use and the agent containing them will be described in more detail.
＜１＞カカオ抽出物を有効成分とする、骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤。 <1> Bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, or CML production inhibitor, comprising cacao extract as an active ingredient.
＜２＞前記抽出物が、カカオの種子の抽出物である、前記＜１＞項に記載の剤。
＜３＞前記抽出物が、水、アルコール類、又はこれらの混合溶媒、好ましくはアルコール水溶液、より好ましくはエタノール水溶液、でカカオを抽出して得られた抽出物である、前記＜１＞又は＜２＞項に記載の剤。
＜４＞前記抽出物が、コラーゲンに対するメイラード反応、好ましくは後期のメイラード反応、を抑制する、前記＜１＞〜＜３＞のいずれか１項に記載の剤。
＜５＞前記剤の総量中、前記有効成分の含有量が、乾燥物換算で、0.1質量％以上、好ましくは1質量％以上、より好ましくは5質量％以上、であり、50質量％以下、好ましくは40質量％以下、より好ましくは20質量%以下、である、前記＜１＞〜＜４＞のいずれか１項に記載の剤。
<2> The agent according to <1>, wherein the extract is an extract of cacao seeds.
<3> The <1> or <1>, wherein the extract is an extract obtained by extracting cacao with water, alcohols, or a mixed solvent thereof, preferably an alcohol aqueous solution, more preferably an ethanol aqueous solution. Item 2>.
<4> The agent according to any one of <1> to <3>, wherein the extract suppresses a Maillard reaction to collagen, preferably a late Maillard reaction.
<5> In the total amount of the agent, the content of the active ingredient is 0.1% by mass or more, preferably 1% by mass or more, more preferably 5% by mass or more in terms of dry matter, and 50% by mass or less. The agent according to any one of <1> to <4>, preferably 40% by mass or less, more preferably 20% by mass or less.
＜６＞骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤としての、カカオ抽出物の使用。
＜７＞骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤の製造のための、カカオ抽出物の使用。
＜８＞カカオ抽出物を、骨強度改善剤、骨質改善剤、皮膚老化予防若しくは改善剤、メイラード反応抑制剤、AGEs生成阻害剤、ペントシジン生成阻害剤、又はCML生成阻害剤として使用する方法。
＜９＞カカオ抽出物を適用する、骨強度改善方法、骨質改善方法、皮膚老化予防若しくは改善剤、メイラード反応抑制方法、AGEs生成阻害方法、ペントシジン生成阻害方法、又はCML生成阻害方法。
<6> Use of cacao extract as an agent for improving bone strength, an agent for improving bone quality, an agent for preventing or improving skin aging, a Maillard reaction inhibitor, an AGEs production inhibitor, a pentosidine production inhibitor, or a CML production inhibitor.
<7> Use of cacao extract for production of bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, or CML production inhibitor .
<8> A method of using a cacao extract as a bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, or CML production inhibitor.
<9> A bone strength improving method, a bone quality improving method, a skin aging preventive or improving agent, a Maillard reaction suppressing method, an AGEs production inhibiting method, a pentosidine production inhibiting method, or a CML production inhibiting method, to which a cacao extract is applied.
＜１０＞前記抽出物が、カカオの種子の抽出物である、前記＜６＞〜＜９＞のいずれか１項に記載の使用又は方法。
＜１１＞前記抽出物が、水、アルコール類、又はこれらの混合溶媒、好ましくはアルコール水溶液、より好ましくはエタノール水溶液、でカカオを抽出して得られた抽出物である、前記＜６＞〜＜１０＞のいずれか１項に記載の使用又は方法。
＜１２＞前記抽出物が、コラーゲンに対するメイラード反応、好ましくは後期のメイラード反応、を抑制する、前記＜６＞〜＜１１＞のいずれか１項に記載の使用又は方法。
＜１３＞前記抽出物を、骨強度改善効果、骨質改善効果、皮膚老化予防若しくは改善剤、メイラード反応抑制効果、AGEs生成阻害効果、ペントシジン生成阻害効果、又はCML生成阻害効果を所望する対象者に適用する、前記＜６＞〜＜１２＞のいずれか１項に記載の方法。
＜１４＞コラーゲンに対するメイラード反応が亢進又は惹起されている条件下、又はコラーゲン由来のAGEsの生成が促進されている条件下で前記抽出物を適用する、前記＜６＞〜＜１３＞のいずれか１項に記載の使用又は方法。
＜１５＞前記剤の総量中、前記抽出物の含有量が、乾燥物換算で、0.1質量％以上、好ましくは1質量％以上、より好ましくは5質量％以上、であり、50質量％以下、好ましくは40質量％以下、より好ましくは20質量%以下、である、前記＜６＞〜＜２８＞のいずれか１項に記載の使用又は方法。
＜１６＞前記抽出物の投与又は摂取量が、乾燥物換算で、100mg/kg体重/日以上、好ましくは500mg/kg体重/日以上、であり、10,000mg/kg体重/日以下、好ましくは5,000mg/kg体重/日以下、である、前記＜６＞〜＜１５＞のいずれか１項に記載の使用又は方法。
<10> The use or method according to any one of <6> to <9>, wherein the extract is an extract of cacao seeds.
<11> The <6> to <6>, wherein the extract is an extract obtained by extracting cacao with water, alcohols, or a mixed solvent thereof, preferably an alcohol aqueous solution, more preferably an ethanol aqueous solution. 10. The use or method according to any one of 10>.
<12> The use or method according to any one of <6> to <11>, wherein the extract suppresses a Maillard reaction to collagen, preferably a late Maillard reaction.
<13> For the subject who desires the bone strength improving effect, bone quality improving effect, skin aging preventive or improving agent, Maillard reaction inhibitory effect, AGEs production inhibitory effect, pentosidine production inhibitory effect, or CML production inhibitory effect. The method according to any one of <6> to <12>, which is applied.
<14> Any one of the above <6> to <13>, wherein the extract is applied under conditions where the Maillard reaction to collagen is enhanced or induced, or under conditions where the production of collagen-derived AGEs is promoted Use or method according to paragraph 1.
<15> In the total amount of the agent, the content of the extract is 0.1% by mass or more, preferably 1% by mass or more, more preferably 5% by mass or more in terms of dry matter, and 50% by mass or less. The use or method according to any one of <6> to <28>, preferably 40% by mass or less, more preferably 20% by mass or less.
<16> The administration or intake of the extract is 100 mg / kg body weight / day or more, preferably 500 mg / kg body weight / day or more, preferably 10,000 mg / kg body weight / day or less, preferably in terms of dry matter. The use or method according to any one of <6> to <15>, which is 5,000 mg / kg body weight / day or less.
＜１７＞骨強度改善方法、骨質改善方法、皮膚老化予防若しくは改善方法、メイラード反応抑制方法、AGEs生成阻害方法、ペントシジン生成阻害方法、又はCML生成阻害方法のために用いる、カカオ抽出物。
＜１８＞骨強度改善薬、骨質改善薬、皮膚老化予防若しくは改善薬、メイラード反応抑制薬、AGEs生成阻害薬、ペントシジン生成阻害薬、又はCML生成阻害薬の製造のための、カカオ抽出物の使用。
＜１９＞骨強度改善、骨質改善、皮膚老化予防若しくは改善、メイラード反応抑制、AGEs生成阻害、ペントシジン生成阻害、又はCML生成阻害の非治療的な処置方法のために用いる、カカオ抽出物の使用。
<17> A cacao extract used for a bone strength improvement method, bone quality improvement method, skin aging prevention or improvement method, Maillard reaction suppression method, AGEs production inhibition method, pentosidine production inhibition method, or CML production inhibition method.
<18> Use of cacao extract for production of bone strength improving agent, bone quality improving agent, skin aging prevention or improving agent, Maillard reaction inhibitor, AGEs production inhibitor, pentosidine production inhibitor, or CML production inhibitor .
<19> Use of cacao extract used for non-therapeutic treatment methods for bone strength improvement, bone quality improvement, skin aging prevention or improvement, Maillard reaction inhibition, AGEs production inhibition, pentosidine production inhibition, or CML production inhibition.
＜２０＞前記抽出物が、カカオの種子の抽出物である、前記＜１７＞〜＜１９＞のいずれか１項に記載の抽出物又は使用。
＜２１＞前記抽出物が、水、アルコール類、又はこれらの混合溶媒、好ましくはアルコール水溶液、より好ましくはエタノール水溶液、でカカオを抽出して得られた抽出物である、前記＜１７＞〜＜２０＞のいずれか１項に記載の抽出物又は使用。
＜２２＞前記抽出物が、コラーゲンに対するメイラード反応、好ましくは後期のメイラード反応、を抑制する、前記＜１７＞〜＜２１＞のいずれか１項に記載の抽出物又は使用。
＜２３＞前記抽出物を、骨強度改善効果、骨質改善効果、皮膚老化予防若しくは改善効果、メイラード反応抑制効果、AGEs生成阻害効果、ペントシジン生成阻害効果、又はCML生成阻害効果を所望する対象者に適用する、前記＜１７＞〜＜２２＞のいずれか１項に記載の抽出物又は使用。
＜２４＞コラーゲンに対するメイラード反応が亢進又は惹起されている条件下、又はコラーゲン由来のAGEsの生成が促進されている条件下で前記抽出物を適用する、前記＜１７＞〜＜２３＞のいずれか１項に記載の抽出物又は使用。
＜２５＞前記抽出物を医薬組成物又は化粧料組成物の形態で適用する、前記＜１７＞〜＜２４＞のいずれか１項に記載の抽出物又は使用。
＜２６＞前記抽出物を食品組成物の形態で適用する、前記＜１７＞〜＜２４＞のいずれか１項に記載の抽出物又は使用。
＜２７＞前記組成物の総量に対する前記抽出物の含有量が、乾燥物換算で、0.1質量％以上、好ましくは1質量％以上、より好ましくは5質量％以上、であり、50質量％以下、好ましくは40質量％以下、より好ましくは20質量%以下、である、前記＜２５＞又は＜２６＞項に記載の抽出物又は使用。
＜２８＞前記抽出物の投与又は摂取量が、乾燥物換算で、100mg/kg体重/日以上、好ましくは500mg/kg体重/日以上、であり、10,000mg/kg体重/日以下、好ましくは5,000mg/kg体重/日以下、である、前記＜１７＞〜＜２７＞のいずれか１項に記載の抽出物又は使用。
<20> The extract or use according to any one of <17> to <19>, wherein the extract is an extract of cacao seeds.
<21> Said <17> to <17>, wherein the extract is an extract obtained by extracting cacao with water, alcohols, or a mixed solvent thereof, preferably an alcohol aqueous solution, more preferably an ethanol aqueous solution. 20. The extract or use according to any one of 20>.
<22> The extract or the use according to any one of <17> to <21>, wherein the extract suppresses a Maillard reaction to collagen, preferably a late Maillard reaction.
<23> To the subject who desires the bone strength improving effect, bone quality improving effect, skin aging prevention or improving effect, Maillard reaction suppressing effect, AGEs generation inhibitory effect, pentosidine generation inhibitory effect, or CML generation inhibitory effect. The extract or use according to any one of <17> to <22>, which is applied.
<24> Any one of the above <17> to <23>, wherein the extract is applied under conditions where the Maillard reaction to collagen is enhanced or induced, or under conditions where the production of collagen-derived AGEs is promoted 2. Extract or use according to item 1.
<25> The extract or use according to any one of <17> to <24>, wherein the extract is applied in the form of a pharmaceutical composition or a cosmetic composition.
<26> The extract or use according to any one of <17> to <24>, wherein the extract is applied in the form of a food composition.
<27> The content of the extract with respect to the total amount of the composition is 0.1% by mass or more, preferably 1% by mass or more, more preferably 5% by mass or more, and 50% by mass or less, in terms of dry matter. The extract or use according to <25> or <26>, preferably 40% by mass or less, more preferably 20% by mass or less.
<28> The administration or intake of the extract is 100 mg / kg body weight / day or more, preferably 500 mg / kg body weight / day or more, preferably 10,000 mg / kg body weight / day or less, preferably in terms of dry matter. The extract or use according to any one of <17> to <27>, which is 5,000 mg / kg body weight / day or less.
＜２９＞カカオ抽出物を適用する、非治療的な骨強度改善方法、非治療的な骨質改善方法、非治療的な皮膚老化予防若しくは改善方法、非治療的なメイラード反応抑制方法、非治療的なAGEs生成阻害方法、非治療的なペントシジン生成阻害方法、又は非治療的なCML生成阻害方法。
＜３０＞前記抽出物が、カカオの種子の抽出物である、前記＜２９＞項に記載の方法。
＜３１＞前記抽出物が、水、アルコール類、又はこれらの混合溶媒、好ましくはアルコール水溶液、より好ましくはエタノール水溶液、でカカオを抽出して得られた抽出物である、前記＜２９＞又は＜３０＞項に記載の方法。
＜３２＞前記抽出物が、コラーゲンに対するメイラード反応、好ましくは後期のメイラード反応、を抑制する、前記＜２９＞〜＜３１＞のいずれか１項に記載の方法。
＜３３＞前記抽出物を、骨強度改善効果、骨質改善効果、皮膚老化予防若しくは改善効果、メイラード反応抑制効果、AGEs生成阻害効果、ペントシジン生成阻害効果、又はCML生成阻害効果を所望する対象者に適用する、前記＜２９＞〜＜３２＞のいずれか１項に記載の方法。
＜３４＞コラーゲンに対するメイラード反応が亢進又は惹起されている条件下、又はコラーゲン由来のAGEsの生成が促進されている条件下で前記抽出物を適用する、前記＜２９＞〜＜３３＞のいずれか１項に記載の方法。
＜３５＞前記抽出物の投与又は摂取量が、乾燥物換算で、100mg/kg体重/日以上、好ましくは500mg/kg体重/日以上、であり、10,000mg/kg体重/日以下、好ましくは5,000mg/kg体重/日以下、である、前記＜２９＞〜＜３４＞のいずれか１項に記載の方法。
<29> Application of cacao extract, non-therapeutic bone strength improvement method, non-therapeutic bone quality improvement method, non-therapeutic skin aging prevention or improvement method, non-therapeutic Maillard reaction suppression method, non-therapeutic AGEs production inhibition method, non-therapeutic pentosidine production inhibition method, or non-therapeutic CML production inhibition method.
<30> The method according to <29>, wherein the extract is an extract of cacao seeds.
<31> The above <29> or <31>, wherein the extract is an extract obtained by extracting cacao with water, alcohols, or a mixed solvent thereof, preferably an alcohol aqueous solution, more preferably an ethanol aqueous solution. Item 30>.
<32> The method according to any one of <29> to <31>, wherein the extract suppresses a Maillard reaction to collagen, preferably a late Maillard reaction.
<33> For the subject who desires the bone strength improving effect, bone quality improving effect, skin aging prevention or improving effect, Maillard reaction suppressing effect, AGEs generation inhibitory effect, pentosidine generation inhibitory effect, or CML generation inhibitory effect. The method according to any one of <29> to <32>, which is applied.
<34> Any of the above <29> to <33>, wherein the extract is applied under a condition where the Maillard reaction to collagen is enhanced or induced, or under conditions where the production of collagen-derived AGEs is promoted 2. The method according to item 1.
<35> The administration or intake of the extract is 100 mg / kg body weight / day or more, preferably 500 mg / kg body weight / day or more in terms of dry matter, preferably 10,000 mg / kg body weight / day or less, preferably The method according to any one of <29> to <34>, which is 5,000 mg / kg body weight / day or less.
＜３６＞前記＜１＞〜＜５＞のいずれか１項に記載の剤を有効成分として含有する、骨強度改善用食品組成物、骨質改善用食品組成物、皮膚老化予防若しくは改善用食品組成物、メイラード反応抑制用食品組成物、AGEs生成阻害用食品組成物、ペントシジン生成阻害用食品組成物、又はCML生成阻害用食品組成物。
＜３７＞カカオ抽出物を有効成分として含有する、骨強度改善用食品組成物、骨質改善用食品組成物、皮膚老化予防若しくは改善用食品組成物、メイラード反応抑制用食品組成物、AGEs生成阻害用食品組成物、ペントシジン生成阻害用食品組成物、又はCML生成阻害用食品組成物。
＜３８＞カカオ抽出物を有効成分として含有する、メイラード反応抑制用化粧料組成物、AGEs生成阻害用化粧料組成物、ペントシジン生成阻害用化粧料組成物、CML生成阻害用化粧料組成物。
＜３９＞前記抽出物が、カカオの種子の抽出物である、前記＜３７＞又は＜３８＞項に記載の組成物。
＜４０＞前記抽出物が、水、アルコール類、又はこれらの混合溶媒、好ましくはアルコール水溶液、より好ましくはエタノール水溶液、でカカオを抽出して得られた抽出物である、前記＜３７＞〜＜３９＞のいずれか１項に記載の組成物。
＜４１＞前記抽出物が、コラーゲンに対するメイラード反応、好ましくは後期のメイラード反応、を抑制する、前記＜３７＞〜＜４０＞のいずれか１項に記載の組成物。
＜４２＞前記組成物の総量中、前記有効成分の含有量が、乾燥物換算で、0.1質量％以上、好ましくは1質量％以上、より好ましくは5質量％以上、であり、50質量％以下、好ましくは40質量％以下、より好ましくは20質量%以下、である、前記＜３７＞〜＜４１＞のいずれか１項に記載の組成物。
<36> A food composition for improving bone strength, a food composition for improving bone quality, a food composition for preventing or improving skin aging, comprising the agent according to any one of <1> to <5> as an active ingredient. Food composition for inhibiting Maillard reaction, food composition for inhibiting AGEs production, food composition for inhibiting pentosidine production, or food composition for inhibiting CML production.
<37> Food composition for improving bone strength, food composition for improving bone quality, food composition for preventing or improving skin aging, food composition for inhibiting Maillard reaction, for inhibiting AGEs formation, containing cacao extract as an active ingredient A food composition, a food composition for inhibiting pentosidine production, or a food composition for inhibiting CML production.
<38> A cosmetic composition for Maillard reaction suppression, a cosmetic composition for inhibiting AGEs production, a cosmetic composition for inhibiting pentosidine production, and a cosmetic composition for inhibiting CML production, comprising a cacao extract as an active ingredient.
<39> The composition according to <37> or <38>, wherein the extract is an extract of cacao seeds.
<40> The above <37> to <37, wherein the extract is an extract obtained by extracting cacao with water, alcohols, or a mixed solvent thereof, preferably an alcohol aqueous solution, more preferably an ethanol aqueous solution. 39> The composition according to any one of 39>.
<41> The composition according to any one of <37> to <40>, wherein the extract suppresses a Maillard reaction to collagen, preferably a late Maillard reaction.
<42> In the total amount of the composition, the content of the active ingredient is 0.1% by mass or more, preferably 1% by mass or more, more preferably 5% by mass or more in terms of dry matter, and 50% by mass or less. The composition according to any one of <37> to <41>, preferably 40% by mass or less, more preferably 20% by mass or less.
以下、本発明を実施例に基づき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 Hereinafter, although this invention is demonstrated further in detail based on an Example, this invention is not limited to this.
調製例１ カカオ抽出物の調製
カカオの種子を含水エタノールで抽出して得られた粉末（商品名：カカオエキス-P、オリザ油化社製）0.1gに50％(v/v)エタノール水溶液9.9mLを加え、4℃で一晩撹拌しながら抽出した。抽出後遠心分離を行い、上清を回収し、カカオ抽出物を得た。
Preparation Example 1 Preparation of cacao extract 50% (v / v) ethanol aqueous solution in 0.1 g of powder obtained by extracting cacao seeds with hydrous ethanol (trade name: cacao extract-P, manufactured by Oriza Oil Chemical Co., Ltd.) 9.9 mL was added and extracted at 4 ° C. with stirring overnight. Centrifugation was performed after extraction, and the supernatant was collected to obtain a cocoa extract.
実施例１ 蛍光性AGEs生成阻害試験
Hori M.，et al.，Anti-Aging Medicine，2012，vol．9(5)，p．125-134に記載の方法に準じて、コラーゲンを用いた抗糖化測定を行った。
0.25Mリン酸緩衝液（pH7.4）を用いて、0.6Mグルコース溶液と0.75mg/mLウシコラーゲン溶液（コラーゲンタイプＩウシ真皮由来、ニッピ社製）を調製した。
96穴ブラックプレートに前記コラーゲン溶液を45μLずつ分注し、前記グルコース溶液及び／又は前記リン酸緩衝液45μLを添加した。さらに、前記調製例１で調製したカカオ抽出物を終濃度が0.0025％(v/v)、0.005％(v/v)又は0.01％(v/v)となるように10μLを添加した。混合した後、60℃の湿潤インキュベーターで、10日間糖化反応を行った。また、コントロールとして、抽出物の代わりに前記リン酸緩衝液を添加したものを用いた。
Example 1 Fluorescence AGEs production inhibition test
Hori M., et al., Anti-Aging Medicine, 2012, vol. 9 (5), p. In accordance with the method described in 125-134, anti-glycation measurement using collagen was performed.
A 0.6 M glucose solution and a 0.75 mg / mL bovine collagen solution (derived from collagen type I bovine dermis, manufactured by Nippi) were prepared using 0.25 M phosphate buffer (pH 7.4).
45 μL of the collagen solution was dispensed into a 96-well black plate, and 45 μL of the glucose solution and / or the phosphate buffer was added. Furthermore, 10 μL of the cocoa extract prepared in Preparation Example 1 was added so that the final concentration was 0.0025% (v / v), 0.005% (v / v), or 0.01% (v / v). After mixing, the saccharification reaction was performed for 10 days in a wet incubator at 60 ° C. Moreover, what added the said phosphate buffer instead of the extract was used as control.
糖化反応により生成されるAGEs由来の蛍光強度を、蛍光測定プレートリーダーで測定した（励起波長370nm、蛍光波長440nm）。そして、前記調製例１で調製したカカオ抽出物による抗糖化率を下記式より測定した。その結果を表１に示す。
抗糖化率（％）＝（A-A0)/(B-B0)×100
A：コラーゲン、グルコース及びカカオ抽出物を含む反応系における蛍光強度
A0：コラーゲン及びカカオ抽出物を含む反応系における蛍光強度
B：コラーゲン、グルコース及び緩衝液を含む反応系における蛍光強度
B0：コラーゲン及び緩衝液を含む反応系における蛍光強度
The fluorescence intensity derived from AGEs produced by the saccharification reaction was measured with a fluorescence measuring plate reader (excitation wavelength 370 nm, fluorescence wavelength 440 nm). And the anti-glycation rate by the cocoa extract prepared in the said preparation example 1 was measured from the following formula. The results are shown in Table 1.
Anti-glycation rate (%) = (AA 0 ) / (BB 0 ) × 100
A: Fluorescence intensity in reaction system containing collagen, glucose and cocoa extract
A 0 : fluorescence intensity in a reaction system containing collagen and cacao extract
B: Fluorescence intensity in a reaction system containing collagen, glucose and buffer
B 0 : Fluorescence intensity in reaction system containing collagen and buffer
表１に示すように、カカオ抽出物の添加によりコラーゲンの糖化が抑制された。また、カカオ抽出物の濃度が高いほど、コラーゲンの糖化がいっそう抑制された。
以上のように、カカオ抽出物に、コラーゲン由来のAGEsの生成阻害作用が認められた。さらに、カカオ抽出物は、濃度依存的にAGEsの生成を阻害する。
As shown in Table 1, collagen saccharification was suppressed by the addition of the cocoa extract. Moreover, the saccharification of collagen was further suppressed as the concentration of the cocoa extract was higher.
As described above, the cacao extract was found to have an inhibitory effect on the production of collagen-derived AGEs. Furthermore, cocoa extract inhibits the production of AGEs in a concentration-dependent manner.
実施例２ ペントシジン生成阻害試験
実施例１で得られた糖化反応液中に含まれるペントシジン生成量を、FSKペントシジンELISAキット（伏見製薬所社製)で測定した。
糖化反応液12.5μLと酵素液（プロテアーゼ）25μLを混合し、55℃で90分間反応させた。反応後、直ちに100℃、15分間で処理し、酵素を失活させた。冷却後、補助液12.5μLを添加して反応液とした。
ペントシジンを固相化した96穴マイクロプレートに前記反応液を50μL添加し、一次抗体を50μLずつ分注した。37℃で60分間反応させた後、洗浄液で3回、プレートを洗浄した。その後、二次抗体を100μLずつ分注して室温にて60分間反応させた。洗浄操作を3回行った後、発色剤を100μLずつ分注して遮光し、10分間反応させた。反応停止液を100μL添加した後、450nmの吸光度を測定した。そして、糖化反応で生成したペントシジン量をペントシジン標準曲線より定量した。
その結果を表２に示す。
Example 2 Pentosidine Production Inhibition Test The amount of pentosidine produced in the saccharification reaction solution obtained in Example 1 was measured with an FSK pentosidine ELISA kit (Fushimi Pharmaceutical Co., Ltd.).
12.5 μL of the saccharification reaction solution and 25 μL of the enzyme solution (protease) were mixed and reacted at 55 ° C. for 90 minutes. Immediately after the reaction, the enzyme was inactivated by treatment at 100 ° C. for 15 minutes. After cooling, 12.5 μL of auxiliary liquid was added to prepare a reaction liquid.
50 μL of the reaction solution was added to a 96-well microplate on which pentosidine was immobilized, and 50 μL of the primary antibody was dispensed. After reacting at 37 ° C. for 60 minutes, the plate was washed three times with a washing solution. Thereafter, 100 μL of the secondary antibody was dispensed and reacted at room temperature for 60 minutes. The washing operation was performed three times, and then 100 μL of the color former was dispensed in the dark, and allowed to react for 10 minutes. After adding 100 μL of the reaction stop solution, the absorbance at 450 nm was measured. And the amount of pentosidine produced | generated by saccharification reaction was quantified from the pentosidine standard curve.
The results are shown in Table 2.
表２に示すように、カカオ抽出物の添加によりペントシジンの生成が阻害された。また、カカオ抽出物の濃度が高いほど、ペントシジンの生成がいっそう阻害された。
以上のように、カカオ抽出物に、コラーゲン由来のペントシジンの生成阻害作用が認められた。さらに、カカオ抽出物は、濃度依存的にペントシジンの生成を阻害する。
As shown in Table 2, the addition of cacao extract inhibited the production of pentosidine. Moreover, the higher the concentration of the cocoa extract, the more inhibited the production of pentosidine.
As described above, the cacao extract was found to have an inhibitory effect on the production of collagen-derived pentosidine. Furthermore, the cocoa extract inhibits the production of pentosidine in a concentration-dependent manner.
実施例３ CML生成阻害試験
実施例１で得られた糖化反応液中に含まれるCML生成量を、CML/Nε-(Carboxymethyl)lysine ELISAキット（サイクレックス社製）で測定した。
糖化反応液60μLと抗CMLモノクロナール抗体（一次抗体）溶液60μLを混合した。そして、CMLが固相化された96穴マイクロプレートに、混合液100μLを分注した。室温で60分間撹拌しながら反応させた後、洗浄液で4回、プレートを洗浄した。その後、二次抗体を100μLずつ分注して室温にて60分間撹拌しながら反応させた。洗浄操作を4回行った後、発色剤を100μLずつ分注して遮光し、室温で20分間撹拌しながら反応させた。反応停止液を100μL添加した後、450nmの吸光度を測定した。糖化反応で生成したCML量をCML標準曲線より定量した。
その結果を表３に示す。
Example 3 CML Production Inhibition Test The amount of CML produced contained in the saccharification reaction solution obtained in Example 1 was measured with a CML / N ε- (Carboxymethyl) lysine ELISA kit (manufactured by Cyclex).
60 μL of the saccharification reaction solution and 60 μL of the anti-CML monoclonal antibody (primary antibody) solution were mixed. And 100 microliters of liquid mixtures were dispensed to the 96-well microplate by which CML was solid-phased. After reacting with stirring for 60 minutes at room temperature, the plate was washed four times with a washing solution. Subsequently, 100 μL of the secondary antibody was dispensed and reacted at room temperature with stirring for 60 minutes. After four washing operations, 100 μL of the color former was dispensed in the dark, light-shielded, and reacted at room temperature with stirring for 20 minutes. After adding 100 μL of the reaction stop solution, the absorbance at 450 nm was measured. The amount of CML produced by the saccharification reaction was quantified from the CML standard curve.
The results are shown in Table 3.
表３に示すように、カカオ抽出物の添加によりCMLの生成が阻害された。 As shown in Table 3, the addition of the cocoa extract inhibited the production of CML.
以上のように、カカオ抽出物は、ペントシジン、CMLなどのAGEsの生成を阻害する作用を有する。よってカカオ抽出物は、骨強度、特に骨質の改善に有用である。また、皮膚老化の予防又は改善にも有効である。 As described above, the cacao extract has an action of inhibiting the generation of AGEs such as pentosidine and CML. Therefore, the cocoa extract is useful for improving bone strength, particularly bone quality. It is also effective in preventing or improving skin aging.
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| JP2022173364A (en) * | 2018-12-13 | 2022-11-18 | 株式会社ノエビア | Skin external preparation |
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