JP2005068129A - Edible composition having promoting activity against production and release of calcitonin gene-associated peptide - Google Patents

Edible composition having promoting activity against production and release of calcitonin gene-associated peptide Download PDF

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JP2005068129A
JP2005068129A JP2004113228A JP2004113228A JP2005068129A JP 2005068129 A JP2005068129 A JP 2005068129A JP 2004113228 A JP2004113228 A JP 2004113228A JP 2004113228 A JP2004113228 A JP 2004113228A JP 2005068129 A JP2005068129 A JP 2005068129A
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capsaicin
edible composition
calcitonin gene
related peptide
isoflavones
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JP4213617B2 (en
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Kenji Okajima
研二 岡嶋
Toshiya Toda
登志也 戸田
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Fujicco Co Ltd
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Fujicco Co Ltd
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Abstract

<P>PROBLEM TO BE SOLVED: To obtain an edible composition having effects of preventing and treating gastric mucosa failure, lifestyle-related diseases, obesity, malignant tumor and osteoporosis, reducing organ transplant rejection reactions, preventing and reducing organ failure accompnied with living body invasion reactions against invading factors such as infections and further having a hair restoration effect, also gentle to a human body and having no adverse effect. <P>SOLUTION: This edible composition having a promoting activity against production and release of a calcitonin-associated peptide contains isoflavone and capsaicin as essential components. The edible composition is used for preventing and treating the gastric mucosa failure, lifestyle-related diseases, obesity, malignant tumor and osteoporosis, reducing the organ transplant rejection reactions, preventing and reducing the organ failure accompanied with the living body invasion reactions against the invading factors such as the infections and further restoring the hair, and the like. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

本発明は、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有する可食性組成物に関する。詳しくは、本発明は、胃粘膜傷害,生活習慣病,肥満,悪性腫瘍等の発生予防と治療用、骨粗鬆症の予防と治療用、臓器移植拒絶反応軽減用、感染等の侵襲要因に対する生体侵襲反応に伴う臓器障害の予防と軽減用、ならびに、育毛用等の、可食性組成物に関するものである。   The present invention relates to an edible composition having a calcitonin gene-related peptide production and release promoting action. Specifically, the present invention relates to a bioinvasive response to invasive factors such as gastric mucosal injury, lifestyle-related diseases, obesity, malignant tumors, etc., prevention and treatment, osteoporosis prevention and treatment, organ transplant rejection reduction, infection, etc. The present invention relates to an edible composition for prevention and reduction of organ damage associated with hair and for hair growth.

現代社会においては、多かれ少なかれ生体の内部環境を撹乱させるような社会的、心理的および身体的なストレスを避けて生活することはできない。ストレスと疾病の関連の重要性は、社会的心理的ストレッサーが、その発症に深くかかわっている病態、すなわち消化性潰瘍、過敏性大腸症候群、気管支喘息、高血圧、虚血性心疾患および糖尿病などにおいて指摘されてきたが、これらのほかにも、社会的心理的ストレスにより免疫能が低下し、感染症や発癌などのリスクが増加することも知られている。また、薄毛、抜け毛に悩む男女が増加しているが、これも、遺伝的素因、老化などの要因以外に、ストレスの影響が大きいことが指摘されている。   In modern society, it is impossible to live avoiding social, psychological and physical stress that more or less disturbs the internal environment of the living body. The importance of the relationship between stress and illness has been pointed out by social and psychological stressors in conditions that are deeply involved in their development, such as peptic ulcer, irritable bowel syndrome, bronchial asthma, hypertension, ischemic heart disease and diabetes However, in addition to these, it is also known that immunity decreases due to social and psychological stress, and the risk of infections and cancers increases. In addition, the number of men and women suffering from thinning hair and hair loss is increasing, but it has been pointed out that this is also influenced by stress in addition to factors such as genetic predisposition and aging.

一方、感染や外傷などといった、身体への物理化学的ストレッサーに対する生体反応は、社会的心理的ストレッサーに対する生体反応と極めて類似しており、これらの生体反応の発現にTNF−αなどの炎症性サイトカインが重要であることが明らかになってきた。   On the other hand, biological reactions to physicochemical stressors to the body, such as infection and trauma, are very similar to those to social psychological stressors, and inflammatory cytokines such as TNF-α are expressed in the expression of these biological reactions. It has become clear that is important.

TNF−αは、基本的にはストレス反応における生体防御に最も重要な役割を果たす物質であり、単球、好中球および血管内皮細胞などを活性化し、炎症反応の拡大に大きく関与する。しかしながら、強力で継続的なストレスにより上記TNF−αの産生が過剰になると、血栓形成などの循環障害や実質細胞のアポトーシスを引き起こすことで臓器機能障害や形態変化などを惹起し、生体をいわゆる悪液質に陥れ、さまざまな疾病症状が現れるようになる。このような観点から、多くの病因をストレッサーと考えれば、それらに対する反応が、その疾病の病態であり、また、臨床症状であると考えることができる。   TNF-α is basically a substance that plays the most important role in living body defense in the stress reaction, activates monocytes, neutrophils, vascular endothelial cells and the like, and is greatly involved in the expansion of the inflammatory response. However, excessive production of TNF-α due to strong and continuous stress causes circulatory disturbances such as thrombus formation and apoptosis of parenchymal cells, thereby causing organ dysfunction and morphological changes, etc. It falls into liquid quality and various disease symptoms appear. From this point of view, if many etiologies are considered stressors, the response to them can be considered to be the pathology of the disease and clinical symptoms.

たとえば、消化性潰瘍の発症は、TNF−αによって惹起される胃粘膜の炎症が重要な原因となっている。また、TNF−αの産生亢進によって、糖尿病、高血圧、高脂血症および動脈硬化などの生活習慣病や、癌、骨粗鬆症の発症リスクが大きくなることが知られている。   For example, the development of peptic ulcer is caused by inflammation of the gastric mucosa caused by TNF-α. Further, it is known that increased production of TNF-α increases the risk of developing lifestyle-related diseases such as diabetes, hypertension, hyperlipidemia and arteriosclerosis, cancer, and osteoporosis.

TNF−αの産生の抑制には、神経ペプチドの一種であるカルシトニン遺伝子関連ペプチドが重要な役割を果たしている。カルシトニン遺伝子関連ペプチドは、ホルモンであるカルシトニンと構造が非常に類似した37個のアミノ酸からなるペプチドで、この遺伝子はカルシトニン遺伝子と同じ遺伝子上にあり、そのオルタナティブ・スプライシング(alternative splicing)により生成される。カルシトニン遺伝子関連ペプチドは、血管拡張作用、骨芽細胞の増殖、また破骨細胞の活性化抑制、食欲の抑制、さらにNFκBの活性化を抑制して、TNF−αの産生抑制や癌細胞のアポトーシスを促進する。また、カルシトニン遺伝子関連ペプチドが血管内皮細胞に作用することにより、NOや、PGI2 などのプロスタグランジンの産生が亢進するが、これらの物質は、血流増加作用に加えてTNF−α産生抑制作用を発揮する。さらに、カルシトニン遺伝子関連ペプチドは、循環器系にも重要な作用を及ぼすことが知られており、全身の血管拡張作用、陽性変時及び変力作用、NaClの体外排泄作用、冠血管拡張作用、及び腎血流増加作用などを有している。 A calcitonin gene-related peptide, which is a kind of neuropeptide, plays an important role in suppressing the production of TNF-α. The calcitonin gene-related peptide is a 37 amino acid peptide that is very similar in structure to the hormone calcitonin, which is on the same gene as the calcitonin gene and is generated by alternative splicing. . Calcitonin gene-related peptide suppresses TNF-α production and apoptosis of cancer cells by suppressing vasodilation, osteoblast proliferation, osteoclast activation inhibition, appetite inhibition, and NFκB activation. Promote. In addition, the production of prostaglandins such as NO and PGI 2 is enhanced by the action of calcitonin gene-related peptides on vascular endothelial cells, but these substances suppress TNF-α production in addition to blood flow increasing action. Demonstrate the effect. Furthermore, calcitonin gene-related peptides are known to have an important effect on the circulatory system, including systemic vasodilatory action, positive chronotropic and inotropic action, NaCl extracorporeal action, coronary vasodilatory action, And has an effect of increasing renal blood flow.

現在、TNF−αの過剰な産生に起因すると考えられる上記疾病の治療に種々の薬剤が用いられている。しかし、多くのものは対症療法的な薬剤であり、病態の主原因にかかわるものではなく、むしろ副作用が問題となる場合が多い。たとえば、消化性潰瘍治療では、H2 ブロッカーのように胃酸分泌を強力に抑制する薬剤が用いられることが多いが、長期に胃酸分泌を抑制すると、胃酸による胃粘膜防御機構が作動しなくなり、胃痛などの自覚症状の改善や胃酸による胃粘膜の表面的な自己消化は軽減されるものの、胃粘膜の炎症は軽減されず、むしろ増悪し、胃粘膜の萎縮やひいては胃癌の発生母地を形成することになる。 Currently, various drugs are used for the treatment of the above-mentioned diseases that are thought to be caused by excessive production of TNF-α. However, many of them are symptomatic drugs and do not relate to the main cause of the pathological condition, but rather side effects are often problematic. For example, in the treatment of peptic ulcer, drugs that strongly suppress gastric acid secretion, such as H 2 blocker, are often used. Although improvement of subjective symptoms such as gastric acid and superficial self-digestion of gastric mucosa by gastric acid are reduced, inflammation of gastric mucosa is not alleviated, but rather aggravates and forms the origin of gastric mucosal atrophy and eventually gastric cancer It will be.

また、ステロイドは、TNF−αの産生を阻害し抗炎症作用を持つが、同時に臓器保護機構を破綻させる。さらに、非ステロイド系抗炎症剤のひとつであるインドメタシンなどは、TNF−αによって誘導される大量のPGE2 の産生を抑制することにより、発熱や痛みや腫れの症状を緩和するが、同時に臓器保護に重要なプロスタグランジンの産生に必要なCOX−1を阻害する。 Steroids also inhibit TNF-α production and have anti-inflammatory effects, but at the same time disrupt organ protection mechanisms. In addition, indomethacin, a non-steroidal anti-inflammatory agent, alleviates the symptoms of fever, pain and swelling by suppressing the production of large amounts of PGE 2 induced by TNF-α, but at the same time protects organs. Inhibits COX-1, which is required for the production of prostaglandins that are important for

ところで、カルシトニン遺伝子関連ペプチドは、先に述べたように、上記悪害をもたらすTNF−αの過剰な産生を抑制するとともに、インスリン様成長因子を誘導する。インスリン様成長因子は、毛包の成長を促進し、毛周期における休止期から成長期への移行と成長期の延長に関して重要な働きをしていると考えられている。
岡嶋研二著「生体侵襲と疾患−重症敗血症から生活習慣病まで」現代医療社、2003年 Harada N、Okajima K 、Uchiba M 、Katsuragi T 、Contribution of capsaicin-sensitive sensory neurons to stress-induced increase in gastric tissue levels of prostaglandins in rats 、 Am J Physiol Gastrointest Liver Physiol、2003 Jul 31 [Epub ahead of print] Vignery A 、McCarthy TL 、The neuropeptide calcitonin gene-related peptide stimulates insulin-like growth factor 1 production by primary fetal rat osteoblasts、Bone、1996、Vol 18、No 4、331-335 Philpott MP 、Sanders DA、Kealey T、Effects of insulin and insulin-like growth factors on cultured human hair follicles: IGF-1 at physiologic concentrations is an important regulator of hair follicle growth in vitro 、J Invest Dermatol 、1994、Vol 102 、No 6、857-861
By the way, as described above, the calcitonin gene-related peptide suppresses excessive production of TNF-α causing the above-mentioned harmful effects and induces an insulin-like growth factor. Insulin-like growth factors are thought to promote hair follicle growth and play an important role in the transition from the resting phase to the growth phase in the hair cycle and the extension of the growth phase.
Kenji Okajima, “Bioinvasion and disease-from severe sepsis to lifestyle-related diseases”, Hyundai Medical Company, 2003 Harada N, Okajima K, Uchiba M, Katsuragi T, Contribution of capsaicin-sensitive sensory neurons to stress-induced increase in gastric tissue levels of prostaglandins in rats, Am J Physiol Gastrointest Liver Physiol, 2003 Jul 31 [Epub ahead of print] Vignery A, McCarthy TL, The neuropeptide calcitonin gene-related peptide stimulates insulin-like growth factor 1 production by primary fetal rat osteoblasts, Bone, 1996, Vol 18, No 4, 331-335 Philpott MP, Sanders DA, Kealey T, Effects of insulin and insulin-like growth factors on cultured human hair follicles: IGF-1 at physiologic concentrations is an important regulator of hair follicle growth in vitro, J Invest Dermatol, 1994, Vol 102, No 6, 857-861

しかしながら、上記のようにTNF−αの過剰な産生を抑制するために用いられてきた従来の薬剤では、副作用を伴うといった問題があることから、人体の健康上好ましいとはいえない。そのため、このような問題を生じず、TNF−α過剰産生の抑制等に重要な役割を果たすカルシトニン遺伝子関連ペプチドの、産生および放出を著明に促進し得る作用を有する可食性組成物が求められている。   However, the conventional drugs that have been used to suppress excessive production of TNF-α as described above are not preferable for human health because of the problem of side effects. Therefore, there is a need for an edible composition that does not cause such problems and has an action that can significantly promote the production and release of a calcitonin gene-related peptide that plays an important role in the suppression of overproduction of TNF-α. ing.

本発明は、このような事情に鑑みなされたもので、胃粘膜傷害,生活習慣病,肥満,悪性腫瘍および骨粗鬆症の予防及び治療効果、臓器移植拒絶反応を軽減する効果、感染等の侵襲要因に対する生体侵襲反応に伴う臓器障害の予防及び軽減効果、さらには育毛効果を有し、しかも人体にやさしく副作用のない自然の成分を用いた可食性組成物の提供をその目的とする。   The present invention has been made in view of such circumstances, and is intended to prevent and treat gastric mucosal injury, lifestyle-related diseases, obesity, malignant tumors and osteoporosis, to reduce organ transplant rejection, and to invasive factors such as infection. An object of the present invention is to provide an edible composition using natural ingredients that have an effect of preventing and reducing organ damage associated with a biologically invasive reaction, a hair-growth effect, and that are gentle to the human body and have no side effects.

本発明者らは、上記の目的を達成するため鋭意検討した結果、イソフラボンとカプサイシンを組み合わせることによってカルシトニン遺伝子関連ペプチドの産生および放出が著明に促進されることを見いだし、本発明を完成するにいたった。   As a result of intensive studies to achieve the above-mentioned object, the present inventors have found that the production and release of calcitonin gene-related peptide are significantly promoted by combining isoflavone and capsaicin, and the present invention has been completed. It was.

すなわち、本発明は、以下の(1)から(11)の、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有する可食性組成物を要旨とするものである。
(1)イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有する可食性組成物。
(2)イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有する、胃粘膜傷害予防及び治療用可食性組成物。
(3)イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有する、生活習慣病予防及び治療用可食性組成物。
(4)イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有する、肥満予防及び治療用可食性組成物。
(5)イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有する、悪性腫瘍発生予防,再発予防及び治療用可食性組成物。
(6)イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有する、骨粗鬆症予防及び治療用可食性組成物。
(7)イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有する、臓器移植拒絶反応軽減用可食性組成物。
(8)イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有する、感染,外傷,手術等の侵襲要因に対する生体侵襲反応に伴う臓器障害の予防及び軽減用可食性組成物。
(9)イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有する、育毛用可食性組成物。
(10)イソフラボンが、大豆由来のイソフラボンである(1)から(9)のいずれかに記載の可食性組成物。
(11)カプサイシンが、唐辛子由来のカプサイシンである(1)から(10)のいずれかに記載の可食性組成物。
That is, the gist of the present invention is the following edible composition having the following calcitonin gene-related peptide production and release promoting actions:
(1) An edible composition having isoflavones and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action.
(2) An edible composition for preventing and treating gastric mucosal injury, comprising isoflavones and capsaicin as essential components, and having a calcitonin gene-related peptide production and release promoting action.
(3) An edible composition for the prevention and treatment of lifestyle-related diseases, comprising isoflavones and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action.
(4) An edible composition for the prevention and treatment of obesity, comprising isoflavones and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action.
(5) An edible composition for malignant tumor prevention, recurrence prevention and treatment, comprising isoflavones and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action.
(6) An edible composition for prophylaxis and treatment of osteoporosis, comprising isoflavones and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action.
(7) An edible composition for reducing organ transplant rejection, comprising isoflavones and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action.
(8) An edible composition for preventing and alleviating organ damage associated with a biological invasive reaction to invasive factors such as infection, trauma, and surgery, having isoflavones and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action.
(9) An edible composition for hair growth comprising isoflavones and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action.
(10) The edible composition according to any one of (1) to (9), wherein the isoflavone is soybean-derived isoflavone.
(11) The edible composition according to any one of (1) to (10), wherein the capsaicin is capsaicin derived from chili.

本発明者らは、水浸拘束ストレス胃粘膜病変モデルにおいて唐辛子の辛味成分のバニロイド化合物のひとつであるカプサイシンによって刺激される知覚神経、すなわちカプサイシン感受性知覚神経が活性化される結果、その神経末端よりカルシトニン遺伝子関連ペプチドが放出され、TNF−αの産生が抑制されると同時に、血管内皮型NO合成酵素(eNOS)を活性化し、NOの産生亢進を介して、PGI2 やPGE2 などのプロスタグランジン及びインスリン様成長因子の生成が亢進することを、先に見いだしている。そして、この作用機構は、胃粘膜の傷害、糖尿病、高血圧、高脂血症および動脈硬化などの生活習慣病や肥満、悪性腫瘍、骨粗鬆症の予防及び治療、臓器移植後の拒絶反応の軽減や様々な侵襲要因に対する生体侵襲反応に伴う臓器障害の予防及び軽減、さらには、男性型脱毛における育毛に対し、有効である。 As a result of activation of sensory nerves stimulated by capsaicin, one of the pungent components of chili pepper, capsaicin, in the water immersion restraint stress gastric mucosal lesion model, The calcitonin gene-related peptide is released and the production of TNF-α is suppressed, and at the same time, vascular endothelial NO synthase (eNOS) is activated, and prostaglandins such as PGI 2 and PGE 2 are activated through enhanced NO production. We have previously found that production of gin and insulin-like growth factors is enhanced. This mechanism of action is used to prevent and treat lifestyle-related diseases such as gastric mucosal injury, diabetes, hypertension, hyperlipidemia, and arteriosclerosis, obesity, malignant tumors, osteoporosis, and reduction of rejection after organ transplantation. It is effective for prevention and reduction of organ damage associated with biological invasive reaction to various invasive factors, and for hair growth in male pattern hair loss.

本発明者らは、このような知見に基づいて、さらに検討を重ねた結果、主に大豆種子に含まれるダイゼイン、ゲニステイン、グリシテイン、ダイズイン、ゲニスチン、グリシチン、6 ”−O−マロニルダイズイン、6 ”−O−マロニルゲニスチン、6 ”−O−マロニルグリシチン、6 ”−O−アセチルダイズイン、6 ”−O−アセチルゲニスチン、6 ”−O−アセチルグリシチンや納豆にみられる6 ”−O−サクシニルダイズイン、6 ”−O−サクシニルゲニスチン及び6 ”−O−サクシニルグリシチンなどのイソフラボン類が神経成長因子(nerve growth factor ;NGF )の産生を増加させることによって、カプサイシン感受性知覚神経のカルシトニン遺伝子関連ペプチドの産生促進作用を著明に増強し、さらに、カプサイシンにより産生が増加したカルシトニン遺伝子関連ペプチドの放出を促進し、それらの結果、TNF−αの産生抑制、NOの産生亢進、プロスタグランジン生成、インスリン様成長因子の産生も促進されることを見いだし、本発明を完成したものである。   As a result of further studies based on such findings, the present inventors have mainly studied daidzein, genistein, glycitein, soybean in, genistin, glycitin, 6 ″ -O-malonyl soybean in, "-O-malonyl genistin, 6" -O-malonyl glycitin, 6 "-O-acetyl soybean in, 6" -O-acetyl genistin, 6 "-O-acetyl glycitin and 6" -O found in natto -Isoflavones such as succinyl soybean in, 6 "-O-succinyl genistin and 6" -O-succinyl glycitin increase the production of nerve growth factor (NGF), thereby increasing the calcitonin of capsaicin-sensitive sensory neurons The production-promoting action of gene-related peptides was significantly enhanced, and the production of capsaicin increased. The release of the tonin gene-related peptide was promoted, and as a result, it was found that TNF-α production suppression, NO production enhancement, prostaglandin production, and insulin-like growth factor production were also promoted, and the present invention was completed. Is.

本発明の、イソフラボンとカプサイシンを必須成分とする可食性組成物は、カルシトニン遺伝子関連ペプチドの産生および放出を促進することによって、胃粘膜傷害を予防及び治療する効果を有するだけでなく、糖尿病、高血圧、高脂血症および動脈硬化などの生活習慣病や肥満、悪性腫瘍の発生予防及び再発予防効果、骨粗鬆症の予防及び治療効果、臓器移植後の拒絶反応の軽減、感染,外傷,手術などの様々な侵襲要因による臓器障害予防または治療、さらには育毛に対して効果を有する。また、本発明のカルシトニン遺伝子関連ペプチド産生および放出促進作用を有する可食性組成物は、食品として長年使用されてきた唐辛子に含まれるカプサイシンと大豆に含まれるイソフラボンを有効成分とするものであり、安全性については問題がなく、その作用も穏やかで副作用の心配がないという利点がある。   The edible composition comprising isoflavones and capsaicin as essential components of the present invention not only has an effect of preventing and treating gastric mucosal injury by promoting production and release of calcitonin gene-related peptide, but also diabetes, hypertension. Life-style related diseases such as hyperlipidemia and arteriosclerosis, obesity, prevention of malignant tumor occurrence and recurrence prevention, prevention and treatment of osteoporosis, reduction of rejection after organ transplantation, infection, trauma, surgery, etc. It is effective for preventing or treating organ damage due to various invasive factors, and for hair growth. In addition, the edible composition having calcitonin gene-related peptide production and release promoting action of the present invention is composed of capsaicin contained in chili peppers that have been used for many years as a food and isoflavone contained in soybeans as active ingredients. There is no problem with sex, and there are advantages that its action is mild and there are no side effects.

つぎに、本発明の実施の形態について詳しく説明する。   Next, embodiments of the present invention will be described in detail.

本発明の可食性組成物は、先にも述べたように、イソフラボンとカプサイシンとの組み合わせに特徴を有するものであり、これら各成分を、必須成分として含有するものである。このような構成によって、カルシトニン遺伝子関連ペプチドの産生および放出が著明に促進されるようになる。ここで、必須成分とは、任意成分に対するものであって、構成上必ず含有される成分のことをいい、量的な制約は受けない。   As described above, the edible composition of the present invention is characterized by a combination of isoflavone and capsaicin, and contains these components as essential components. Such a configuration significantly promotes the production and release of calcitonin gene-related peptides. Here, the essential component refers to an optional component, which is a component that is necessarily contained in terms of configuration, and is not subject to quantitative restrictions.

本発明に用いるイソフラボンの由来は、特に限定されるものではなく、たとえば大豆種子、葛根およびそれらを用いた食品などがあげられる。なかでも大豆の胚軸にはイソフラボンが多量に含まれるため都合が良い。また、納豆などの食品を用いることも可能である。   The origin of the isoflavones used in the present invention is not particularly limited, and examples thereof include soybean seeds, kuzu roots and foods using them. Among them, the hypocotyl of soybean is convenient because it contains a large amount of isoflavone. It is also possible to use foods such as natto.

上記イソフラボンには、ダイゼイン、ゲニステイン、グリシテイン、ダイズイン、ゲニスチン、グリシチン、6 ”−O−マロニルダイズイン、6 ”−O−マロニルゲニスチン、6 ”−O−マロニルグリシチン、6 ”−O−アセチルダイズイン、6 ”−O−アセチルゲニスチン、6 ”−O−アセチルグリシチンや納豆にみられる6 ”−O−サクシニルダイズイン、6 ”−O−サクシニルゲニスチン、6 ”−O−サクシニルグリシチン及びプエラリンなどが含まれる。なお、上記の各種イソフラボンは、本発明において、単独であるいは二種以上併せて用いられる。   The isoflavones include daidzein, genistein, glycitein, soybean in, genistin, glycitin, 6 "-O-malonyl soybean in, 6" -O-malonyl genistin, 6 "-O-malonyl glycitin, 6" -O-acetyl soybean. 6 "-O-acetylgenistine, 6" -O-acetylglycistin, 6 "-O-succinyl soybean in, 6" -O-succinylgenistin, 6 "-O-succinylglycitin and puerarin In addition, the above-mentioned various isoflavones are used alone or in combination of two or more in the present invention.

濃度の高いイソフラボンを使用するため大豆や大豆食品、大豆胚軸、葛根などの抽出物やその精製物を用いることも可能である。イソフラボンを抽出する溶媒は、特に限定されるものではないが、水又はエタノールなどのアルコールを用いるのが好ましい。また、精製の方法は、合成吸着剤やイオン交換樹脂、限外ろ過などを使用することが可能であるが、特に限定されるものではない。抽出液又は精製液は、そのまま使用しても良いが、それらを濃縮した濃縮液、もしくは、抽出液又は精製液を乾燥したあと粉末化したものを使用しても良い。   Since isoflavones with high concentrations are used, it is also possible to use extracts such as soybeans, soybean foods, soybean hypocotyls, kudzu roots, and purified products thereof. The solvent for extracting isoflavones is not particularly limited, but it is preferable to use water or alcohol such as ethanol. The purification method can use a synthetic adsorbent, an ion exchange resin, ultrafiltration, or the like, but is not particularly limited. The extract or purified solution may be used as it is, but a concentrated solution obtained by concentrating them, or a powdered product after drying the extract or purified solution may be used.

本発明に用いるカプサイシンの由来は、特に限定されるものではないが、唐辛子を用いることが望ましい。   The origin of capsaicin used in the present invention is not particularly limited, but it is desirable to use chili.

唐辛子に含まれるカプサイシン類としてカプサイシン、ジヒドロカプサイシン、ノルジヒドロカプサイシン、ホモカプサイシン、ホモジヒドロカプサイシンが知られている。なお、上記の各種カプサイシン類は、本発明において、単独であるいは二種以上併せて用いられる。   As capsaicins contained in chili, capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homocapsaicin, and homodihydrocapsaicin are known. The various capsaicins described above are used alone or in combination of two or more in the present invention.

唐辛子は粉砕、粉末化したものをそのまま使用することができるが、濃度の高いカプサイシンを使用するため工業的に製造された唐辛子抽出物を使用することも可能である。唐辛子を含水エタノールで抽出したトウガラシエキストラクト、ヘキサンやエーテルなどの主として非極性から中間極性有機溶剤で抽出したトウガラシオレオレジン、さらにトウガラシオレオレジンをエタノールで再抽出し、不溶物をろ別したトウガラシアブソリュートなどをその特性に応じて使用することができる。   As for the chili pepper, a pulverized and powdered one can be used as it is. However, since capsaicin having a high concentration is used, an industrially produced chili extract can be used. Pepper extract extracted with water-containing ethanol, chili pepper oleoresin extracted mainly with non-polar to intermediate polar organic solvents such as hexane and ether, and red pepper oleoresin again extracted with ethanol, and insoluble matter was filtered out. Etc. can be used according to their characteristics.

本発明の可食性組成物は、上述のようにして得られたイソフラボンとカプサイシンとを必須成分とするものであり、これらを混合したものをそのまま直接使用してもよいが、一般には、これらを、適当な液状担体に溶解あるいは分散させたり、適当な粉末担体に混合させたものを使用する。そして、上記イソフラボンが有効成分となり得るための含有量は、通常、液剤では0.001〜0.5重量%(以下、「%」と略す)の範囲であると好適であり、粉剤の場合は0.01〜80%の範囲であると好適であり、粒剤の場合は0.01〜40%の範囲であると好適である。また、上記カプサイシンが有効成分となり得るための含有量は、通常、液剤では0.0001〜0.05%の範囲であると好適であり、粉剤の場合は0.0001〜5%の範囲であると好適であり、粒剤の場合は0.0001〜5%の範囲であると好適である。そして、本発明においては、上記イソフラボンとカプサイシンとの割合が重要であり、イソフラボン:カプサイシン=5000:1〜1:10の重量比で含有していると好ましく、より好ましくは、イソフラボン:カプサイシン=500:1〜1:1の重量比の範囲である。すなわち、このような割合で双方が含有していると、双方の相乗効果により、本発明において要求されるカルシトニン遺伝子関連ペプチド産生および放出促進作用が効果的に得られるようになるからである。   The edible composition of the present invention contains the isoflavone and capsaicin obtained as described above as essential components, and a mixture of these may be used directly as it is. Alternatively, a solution dissolved or dispersed in an appropriate liquid carrier or mixed in an appropriate powder carrier is used. The content of the isoflavone that can be an active ingredient is usually 0.001 to 0.5% by weight (hereinafter abbreviated as “%”) for a liquid, and in the case of a powder. It is preferable that it is in the range of 0.01 to 80%, and in the case of granules, it is preferable that it is in the range of 0.01 to 40%. In addition, the content of capsaicin that can be an active ingredient is usually preferably 0.0001 to 0.05% in the case of a liquid agent, and 0.0001 to 5% in the case of a powder. In the case of a granule, it is suitable in the range of 0.0001 to 5%. And in this invention, the ratio of the said isoflavone and capsaicin is important, It is preferable to contain by the weight ratio of isoflavone: capsaicin = 5000: 1 to 1:10, More preferably, isoflavone: capsaicin = 500 : The range of the weight ratio of 1-1: 1. That is, when both are contained in such a ratio, the synergistic effect of both enables the calcitonin gene-related peptide production and release promoting action required in the present invention to be effectively obtained.

本発明の可食性組成物は、人間のみでなく、ペットや家畜等の動物においても、人間に投与した際にみられる前述の作用効果と同様の作用効果が期待されるものである。そして、その投与量は、投与対象とする生物の違い、前述の各種作用効果のうちのいずれを得ることを目的とするのかといった違い、投与される者の性別、体重、年齢等の条件に応じて適宜設定される。例えば、成人に対しては、上記イソフラボンとカプサイシンとの混合物を1日あたり10〜400mgとなるよう、数回に分けて投与することができる。また、ペットや家畜等の動物においては、動物用飼料に上記混合物を0.001〜5%の範囲で含有させ、1 日当たり1〜400mg/kg体重の範囲となるよう投与するのが好ましい。   The edible composition of the present invention is expected not only for humans but also for animals such as pets and livestock, as well as the same effects as those described above when administered to humans. And the dose depends on conditions such as the difference in organisms to be administered, the difference between the above-mentioned various effects and the purpose of obtaining, the sex, weight, age, etc. of the administered person. Is set as appropriate. For example, for an adult, the above-mentioned mixture of isoflavone and capsaicin can be administered in several divided doses so as to be 10 to 400 mg per day. In animals such as pets and livestock, the above mixture is preferably contained in the animal feed in a range of 0.001 to 5% and administered in a range of 1 to 400 mg / kg body weight per day.

本発明のカルシトニン遺伝子関連ペプチド産生および放出促進作用を有する可食性組成物は、上述したようにイソフラボンとカプサイシンを有効成分として含むものであれば、その形状や飲食方法を特に問うものではない。具体的には、飲料や調理食品、デザート、菓子、乳製品、麺類、パン類などの一般的な食品のほか、好ましくは錠剤、粉剤、顆粒剤などの固形物や半固形剤をあげることができる。   The edible composition having the calcitonin gene-related peptide production and release-promoting action of the present invention is not particularly limited as long as it contains isoflavone and capsaicin as active ingredients as described above. Specifically, in addition to general foods such as beverages, cooked foods, desserts, confectionery, dairy products, noodles, breads, preferably solids and semi-solids such as tablets, powders, granules, etc. it can.

イソフラボンとカプサイシン以外の任意成分としては、たとえば、甘味料、塩味料、酸味料、うまみ料などの調味料、乳化剤、分散剤、抗酸化剤、防腐剤、増粘剤、結合剤、香料などがあげられる。また、錠剤や粉剤、顆粒剤などの場合は、賦形剤、結合剤、崩壊剤、皮膜剤、滑沢剤、増量剤、希釈剤、pH調整剤、乳化剤、分散剤、安定化剤、嬌味嬌臭剤、着色剤などが例示できる。   Optional ingredients other than isoflavones and capsaicin include, for example, seasonings such as sweeteners, salting agents, acidulants, umami, emulsifiers, dispersants, antioxidants, preservatives, thickeners, binders, and fragrances. can give. In the case of tablets, powders, granules, etc., excipients, binders, disintegrants, film agents, lubricants, extenders, diluents, pH adjusters, emulsifiers, dispersants, stabilizers, Examples include miso odorants and colorants.

以下に、実施例をあげて本発明を具体的に説明する。   Hereinafter, the present invention will be specifically described with reference to examples.

〔水浸拘束ストレス胃粘膜病変モデルにおけるイソフラボンとカプサイシンによるカルシトニン遺伝子関連ペプチドの産生および放出促進作用と胃粘膜傷害抑制作用の検定〕
5群に分けたウィスター系雄ラット(280〜320g、1群あたり8匹)を24時間絶食させた後、4群については水温22℃の水槽内に設置したストレスゲージに8時間拘束した(水浸拘束群)。拘束後、全群のラットを屠殺し、胃の摘出をおこなった。
[Test of calcitonin gene-related peptide production and release promotion and gastric mucosal injury inhibition by isoflavones and capsaicin in a water-immersion restraint stress gastric mucosa lesion model]
Wistar male rats (280 to 320 g, 8 per group) divided into 5 groups were fasted for 24 hours, and then 4 groups were restrained for 8 hours by a stress gauge installed in a water bath with a water temperature of 22 ° C. (water Immersion restraint group). After restraint, all groups of rats were sacrificed and the stomach was removed.

ここで、上記5群は、後記の表1に示すように、上記絶食前に投与した飼料等から、イソフラボン投与群、カプサイシン投与群、イソフラボン+カプサイシン投与群、非投与群(普通食のみ)のいずれかに属する。すなわち、イソフラボン投与群では、水浸拘束処理前28日よりイソフラボンの摂取量が90mg/kg体重/dayとなるよう大豆胚芽抽出物(フジフラボンP10、フジッコ社製)を添加した飼料で飼育を行った。また、カプサイシン投与群では、カプサイシンを、10%のTween20を含む10%エタノール水溶液に溶かし、水浸拘束の1時間前に経口投与した(カプサイシンとして1mg/kg体重の投与)。さらに、イソフラボン+カプサイシン投与群では、その両方を、上記と同様にして投与した。   Here, as shown in Table 1 below, the above five groups are classified into the isoflavone administration group, the capsaicin administration group, the isoflavone + capsaicin administration group, and the non-administration group (normal diet only) from the feed administered before the fasting. Belonging to one. That is, in the isoflavone administration group, breeding was carried out with a feed supplemented with soybean germ extract (Fujiflavone P10, manufactured by Fujicco Co., Ltd.) so that the intake of isoflavone was 90 mg / kg body weight / day from 28 days before the water immersion restraint treatment. . In the capsaicin administration group, capsaicin was dissolved in a 10% ethanol aqueous solution containing 10% Tween 20, and orally administered 1 hour before water immersion restraint (administration of 1 mg / kg body weight as capsaicin). Furthermore, in the isoflavone + capsaicin administration group, both were administered in the same manner as described above.

そして、上記5群、すなわち、正常群(normal;水浸拘束なし)と対照群(Control;水浸拘束)と3つのテスト群(水浸拘束+イソフラボン、水浸拘束+カプサイシン、水浸拘束+イソフラボン+カプサイシン)から摘出された胃をもとに、その胃部傷害指数、胃部カルシトニン遺伝子関連ペプチド濃度(CGRP)の測定を行った。これらの結果を、下記の表1に併せて示す。なお、各データは、それぞれの群での平均値を示すものである。   Then, the above five groups, that is, a normal group (normal; no water immersion restriction), a control group (Control; water immersion restriction), and three test groups (water immersion restriction + isoflavone, water immersion restriction + capsaicin, water immersion restriction + Based on the stomach excised from isoflavone + capsaicin), the gastric injury index and gastric calcitonin gene-related peptide concentration (CGRP) were measured. These results are also shown in Table 1 below. In addition, each data shows the average value in each group.

上記表1の結果より、イソフラボンとカプサイシンを同時に摂取することは、胃部のカルシトニン遺伝子関連ペプチドの産生を促進し、胃粘膜の傷害を予防及び治療しうることがわかる。   From the results of Table 1 above, it can be seen that simultaneous intake of isoflavone and capsaicin promotes the production of calcitonin gene-related peptide in the stomach and can prevent and treat gastric mucosal injury.

〔胃潰瘍患者への投与試験〕
内視鏡で胃潰瘍が認められている患者を対象とし、1グループ4人の計4グループにわけた。そして、そのうちのグループ1では、イソフラボンを含む錠剤(イソフラボン抽出物;フジッコ社製のフジフラボンP40を使用)の投与により1日40mgのイソフラボンを摂取させ、グループ2では、カプサイシンを含む錠剤の投与により1日1mgのカプサイシンを摂取させた。また、グループ3にはその両方を含む錠剤を投与し、グループ4には擬似錠剤を投与した。これを20日間にわたって行った。
[Administration study for gastric ulcer patients]
Targeting patients with gastric ulcers observed by endoscope, the group was divided into 4 groups, 4 people per group. In Group 1, 40 mg of isoflavone is ingested daily by administration of a tablet containing isoflavone (isoflavone extract; using Fujiflavone P40 manufactured by Fujikko Co.), and in Group 2, 1 is administered by administration of a tablet containing capsaicin. 1 mg of capsaicin was ingested daily. Group 3 was administered with a tablet containing both, and Group 4 was administered a pseudo tablet. This was done for 20 days.

そして、投与期間中の自覚症状の確認を行うとともに、投与終了後、胃の内視鏡検査を行った。この結果を、下記の表2に併せて示す。なお、各データは、それぞれのグループでの平均値を示すものである。   Then, while confirming subjective symptoms during the administration period, an endoscopic examination of the stomach was performed after the administration. The results are also shown in Table 2 below. Each data represents an average value in each group.

上記表2の結果より、イソフラボンとカプサイシンを同時に摂取することで胃潰瘍に対して著明な改善効果が認められた。   From the results of Table 2 above, a significant improvement effect on gastric ulcer was observed by taking isoflavone and capsaicin simultaneously.

〔卵巣摘出ラットにおけるイソフラボンとカプサイシンによるカルシトニン遺伝子関連ペプチドの産生促進作用と骨粗鬆症に対する効果の検定〕
5群に分けた80日齢のSD系雌ラット(1群あたり6匹。なお、上記5群のうちの4群は、卵巣摘出がなされた、摘出後10日目のラット)に、標準食〔カルシウム欠乏飼料(Ca:0.004%、P:0.3%)〕等を投与して、28日間飼育した。その後、1晩(18時間)絶食させ、全群のラットを屠殺し、そこから大腿骨を摘出した。
[Evaluation of the effect of isoflavones and capsaicin on the production of calcitonin gene-related peptide and its effect on osteoporosis in ovariectomized rats]
80 days old SD female rats divided into 5 groups (6 per group. Four groups out of the above 5 groups were rats on the 10th day after the extraction). [Calcium deficient diet (Ca: 0.004%, P: 0.3%)] and the like were administered, and the animals were reared for 28 days. Thereafter, the rats were fasted overnight (18 hours), the rats of all groups were sacrificed, and the femurs were removed therefrom.

ここで、上記5群は、後記の表3に示すように、上記絶食前に投与した飼料等から、イソフラボン投与群、カプサイシン投与群、イソフラボン+カプサイシン投与群、非投与群(標準食のみ)のいずれかに属する。すなわち、イソフラボン投与群では、標準食以外に、1%ヒドロキシプロピルセルロース水溶液に懸濁したダイズインを、飼育期間中、経口投与(ダイズインの摂取量が90mg/kg体重/dayとなるよう投与)した。カプサイシン投与群では、標準食以外に、カプサイシンを10%のTween20を含む10%エタノール水溶液に溶かしたものを、飼育期間中、経口投与(カプサイシンの摂取量が1mg/kg体重/dayとなるよう投与)した。さらに、イソフラボン+カプサイシン投与群では、その両方を投与した。   Here, as shown in Table 3 below, the above five groups are divided into the isoflavone administration group, the capsaicin administration group, the isoflavone + capsaicin administration group, and the non-administration group (standard diet only) from the feed administered before the fasting. Belonging to one. That is, in the isoflavone administration group, in addition to the standard diet, soybean in suspended in a 1% hydroxypropylcellulose aqueous solution was orally administered (administered so that the intake of soybean in would be 90 mg / kg body weight / day) during the breeding period. In the capsaicin administration group, in addition to the standard diet, capsaicin dissolved in 10% ethanol aqueous solution containing 10% Tween 20 was orally administered during the breeding period (administered so that the capsaicin intake was 1 mg / kg body weight / day). )did. Furthermore, both were administered in the isoflavone + capsaicin administration group.

そして、上記5群、すなわち、正常群(normal;卵巣摘出なし)と対照群(Control;卵巣摘出)と3つのテスト群(卵巣摘出+イソフラボン、卵巣摘出+カプサイシン、卵巣摘出+イソフラボン+カプサイシン)から摘出された大腿骨をもとに、その湿重量を測定するとともに、ピクノメーターによりその体積を測定し、骨密度を算出した。また、骨組織のカルシトニン遺伝子関連ペプチド濃度(CGRP)の測定も行った。これらの結果を、下記の表3に併せて示す。なお、各データは、それぞれの群での平均値を示すものである。   And from the above five groups, that is, normal group (normal; no ovariectomy), control group (Control; ovariectomy) and three test groups (ovariectomy + isoflavone, ovariectomy + capsaicin, ovariectomy + isoflavone + capsaicin) Based on the removed femur, its wet weight was measured, and its volume was measured with a pycnometer to calculate the bone density. In addition, calcitonin gene-related peptide concentration (CGRP) in bone tissue was also measured. These results are also shown in Table 3 below. In addition, each data shows the average value in each group.

上記表3の結果より、イソフラボンとカプサイシンを同時に摂取することは、カルシトニン遺伝子関連ペプチドの産生および放出を促進し、骨粗鬆症を予防及び治療しうることがわかる。   From the results in Table 3 above, it can be seen that simultaneous intake of isoflavone and capsaicin promotes the production and release of calcitonin gene-related peptide and can prevent and treat osteoporosis.

〔脳卒中易発症高血圧自然発症ラット(SHR−SP)におけるイソフラボンとカプサイシンによるカルシトニン遺伝子関連ペプチドの産生促進作用と高血圧に対する効果の検定〕
18週齢の雄性SHRSP/lzmラットを、1グループ6匹の計4グループにわけた。そして、そのうちのグループ1は、イソフラボンの摂取量が90mg/kg体重/dayとなるように大豆胚芽抽出物(フジフラボンP40)を添加した飼料で飼育した。グループ2は、カプサイシンの摂取量が1mg/kg体重/dayとなるよう調製した飼料で飼育した。グループ3は、イソフラボンとカプサイシンの両方の投与を行った。グループ4は、対照群とした。
[Production promotion of calcitonin gene-related peptide by isoflavones and capsaicin and its effect on hypertension in stroke-prone spontaneously hypertensive rats (SHR-SP)]
18-week-old male SHRSP / lzm rats were divided into 4 groups of 6 per group. And group 1 of them was reared with a feed supplemented with soybean germ extract (Fujiflavone P40) so that the intake of isoflavone was 90 mg / kg body weight / day. Group 2 was reared with a feed prepared so that the amount of capsaicin was 1 mg / kg body weight / day. Group 3 received both isoflavones and capsaicin. Group 4 served as a control group.

投与50日目の尾部血圧測定で、グループ1は260±5.2mmHg、グループ2は268±10.4mmHg、グループ3は246±4.4mmHg、グループ4は279±3.1mmHgであった(グループ3は、グループ4に対して有意差あり)。また、血中のカルシトニン遺伝子関連ペプチドの測定値もグループ4が最も高かった。これにより、イソフラボンとカプサイシンを同時に投与することは、カルシトニン遺伝子関連ペプチドの産生を促進するため、高血圧に対して効果があることがわかる。   On the 50th day after administration, the blood pressure was measured at 260 ± 5.2 mmHg in group 1, 268 ± 10.4 mmHg in group 2, 246 ± 4.4 mmHg in group 3, and 279 ± 3.1 mmHg in group 4 (group 3 is significantly different from group 4). Group 4 also had the highest measured value of calcitonin gene-related peptide in blood. Thus, it can be seen that simultaneous administration of isoflavone and capsaicin is effective for hypertension because it promotes the production of calcitonin gene-related peptide.

〔卵巣摘出ラットにおけるイソフラボンとカプサイシンによるカルシトニン遺伝子関連ペプチドの産生および放出促進作用と食欲抑制による肥満防止効果の検定〕
5群に分けた80日齢のSD系雌ラット(1群あたり7匹。なお、上記5群のうちの4群は、卵巣摘出がなされた、摘出後10日目のラット)を、28日間飼育した。そして、飼育期間中、飼料は自由に摂取させた。ただし、上記各群に与えた飼料は、後記の表4に示すように、標準食〔カルシウム欠乏飼料(Ca:0.004%、P:0.3%)〕、イソフラボン(標準食にイソフラボン0.25%を添加した飼料)、カプサイシン(標準食にカプサイシン0.005%を添加した飼料)、イソフラボン+カプサイシン(標準食にイソフラボン0.25%とカプサイシン0.005%とを添加した飼料)のいずれかである。
[Test of obesity prevention by suppression of appetite and production of calcitonin gene-related peptide by isoflavones and capsaicin in ovariectomized rats]
80-day-old SD female rats divided into 5 groups (7 rats per group. 4 groups out of the 5 groups were rats that had been ovariectomized and 10 days after excision) for 28 days. Raised. During the breeding period, feed was freely consumed. However, as shown in Table 4 below, the feed given to each of the above groups was a standard diet [calcium-deficient diet (Ca: 0.004%, P: 0.3%)], isoflavone (standard diet with isoflavone 0). Feed with 25% added), capsaicin (feed with 0.005% capsaicin added to the standard diet), isoflavone + capsaicin (feed with standard diet supplemented with 0.25% isoflavone and capsaicin 0.005%) Either.

そして、上記5群、すなわち、正常群(normal;卵巣摘出なし)と対照群(control;卵巣摘出)と3つのテスト群(卵巣摘出+イソフラボン0.25%添加飼料、卵巣摘出+カプサイシン0.005%添加飼料、卵巣摘出+イソフラボン0.25%+カプサイシン0.005%添加飼料)について、平均摂餌量と最終体重の測定を行った。これらの結果を、下記の表4に併せて示す。なお、各データは、それぞれの群での平均値を示すものである。   Then, the above five groups, that is, a normal group (normal; no ovariectomy), a control group (control; ovariectomy), and three test groups (ovariectomy + isoflavone 0.25% added feed, ovariectomy + capsaicin 0.005) % Supplemented feed, ovariectomized + isoflavone 0.25% + capsaicin 0.005% added feed), and the average food intake and final body weight were measured. These results are also shown in Table 4 below. In addition, each data shows the average value in each group.

上記表4の結果より、イソフラボンとカプサイシンを同時に摂取することは、カルシトニン遺伝子関連ペプチドの産生および放出を促進し、食欲を抑制し肥満を予防及び治療しうることがわかる。   From the results of Table 4 above, it can be seen that simultaneous intake of isoflavone and capsaicin can promote the production and release of calcitonin gene-related peptide, suppress appetite, and prevent and treat obesity.

〔大腸癌細胞高転移株を移植して作成した肝転移モデルにおけるイソフラボンとカプサイシンによるカルシトニン遺伝子関連ペプチドの産生促進作用と悪性腫瘍に対する効果の検定〕
4グループに分けた(1グループあたり5匹)所定のラットの脾臓すべてに、ヒト大腸癌細胞高転移株を移植し、肝転移モデルを作成した。癌細胞移植後10日目に肝の虚血再灌流を行い、その後に転移した癌細胞数を計測した。
[Production promotion effect of calcitonin gene-related peptide by isoflavone and capsaicin in liver metastasis model prepared by transplanting colon cancer cell high metastasis strain and test for malignant tumor effect]
Liver metastasis models were created by transplanting human colon cancer cell high-metastasis strains into all spleens of predetermined rats divided into 4 groups (5 per group). On day 10 after cancer cell transplantation, ischemia / reperfusion of the liver was performed, and the number of metastasized cancer cells was counted thereafter.

ところで、癌細胞移植前28日より、上記4グループのうちのグループ1は、イソフラボンの摂取量が90mg/kg体重/dayとなるように大豆胚芽抽出物(フジフラボンP40)を添加した飼料で飼育し、グループ2は、カプサイシンの摂取量が1mg/kg体重/dayとなるよう調製した飼料で飼育した。グループ3は、イソフラボンとカプサイシンの両方の投与を行い、グループ4は、対照群とした。   By the way, from the 28th day before the transplantation of cancer cells, group 1 out of the above 4 groups was bred with a diet supplemented with soybean germ extract (Fujiflavone P40) so that the intake of isoflavone was 90 mg / kg body weight / day. Group 2 was reared with a feed prepared so that the intake of capsaicin was 1 mg / kg body weight / day. Group 3 received both isoflavone and capsaicin, and group 4 served as a control group.

そして、上記のようにして計測した結果、グループ1、2はグループ4と比較して転移癌細胞数が少なかったものの、有意な差ではなかった。これに対して、グループ3は、有意に転移が抑制された。また、カルシトニン遺伝子関連ペプチドの量も他グループよりも高い値を示した。これにより、イソフラボンとカプサイシンを同時に投与することは、カルシトニン遺伝子関連ペプチドの産生を促進し、悪性腫瘍の転移に対して効果があることがわかる。   And as a result of measuring as mentioned above, although the group 1 and 2 had few metastatic cancer cell numbers compared with the group 4, it was not a significant difference. In contrast, in Group 3, metastasis was significantly suppressed. The amount of calcitonin gene-related peptide was also higher than that of other groups. Thus, it can be seen that simultaneous administration of isoflavone and capsaicin promotes the production of calcitonin gene-related peptide and is effective for metastasis of malignant tumors.

〔ラット肝移植モデルにおけるイソフラボンとカプサイシンによるカルシトニン遺伝子関連ペプチドの産生促進作用と高血圧に対する効果の検定〕
4グループに分けた(1グループあたり5匹)所定のラットすべてから摘出した肝を、臓器保存液に24時間保存した後、同系ラットに移植手術を行った。このようにして着生率をみると同時に、抹消血のリンパ球を分離し、FACSにて細胞表面の分子について解析を行った。
[Production promotion of calcitonin gene-related peptide by isoflavones and capsaicin and its effect on hypertension in a rat liver transplantation model]
Livers excised from all predetermined rats divided into 4 groups (5 per group) were stored in organ preservation solution for 24 hours, and then transplanted to syngeneic rats. Thus, at the same time as determining the survival rate, peripheral blood lymphocytes were separated, and the cell surface molecules were analyzed by FACS.

ところで、肝移植前28日より、上記4グループのうちのグループ1は、イソフラボン量が90mg/kg体重/dayとなるように大豆胚芽抽出物(フジフラボンP40)を添加した飼料で飼育し、グループ2は、カプサイシン摂取量が1mg/kg体重/dayとなるよう調製した飼料で飼育した。グループ3は、イソフラボンとカプサイシンの両方の投与を行い、グループ4は、対照群とした。   By the way, from the 28th day before liver transplantation, group 1 out of the above 4 groups was bred with a feed supplemented with soybean germ extract (Fujiflavone P40) so that the amount of isoflavone was 90 mg / kg body weight / day. Were fed with a feed prepared so that the capsaicin intake was 1 mg / kg body weight / day. Group 3 received both isoflavone and capsaicin, and group 4 served as a control group.

そして、上記のようにして実験を行った結果、グループ1、2はグループ4と比較して着生率が若干高かった。これに対して、グループ3は、明らかに着生率が向上し、移植免疫寛容状態になっていることがわかった。また、カルシトニン遺伝子関連ペプチドの量も他グループよりも明らかに高い値を示した。これにより、イソフラボンとカプサイシンを同時に投与することは、カルシトニン遺伝子関連ペプチドの産生を促進し、臓器移植の拒絶反応が軽減されたことがわかる。   And as a result of experimenting as described above, Group 1 and Group 2 had slightly higher growth rates than Group 4. On the other hand, it was found that group 3 was clearly improved in the survival rate and was in a state of tolerance for transplantation. The amount of calcitonin gene-related peptide was also clearly higher than other groups. This shows that simultaneous administration of isoflavone and capsaicin promoted the production of calcitonin gene-related peptide and reduced organ transplant rejection.

〔エンドトキシンによるショックモデルに対するイソフラボンとカプサイシンによるカルシトニン遺伝子関連ペプチドの産生促進作用と血圧低下に対する効果の検定〕
4グループに分けた(1グループあたり5匹)所定のラットすべてに、エンドトキシン5mg/kg体重を静脈注射し、ショックモデルを作成し、血圧の測定を行った。
[Test of production of calcitonin gene-related peptide by isoflavone and capsaicin and effect on blood pressure reduction for endotoxin shock model]
Endotoxin 5 mg / kg body weight was intravenously injected into all predetermined rats divided into 4 groups (5 per group), a shock model was created, and blood pressure was measured.

ところで、エンドトキシン投与前28日より、上記4グループのうちのグループ1は、イソフラボン量が90mg/kg体重/dayとなるように大豆胚芽抽出物(フジフラボンP40)を添加した飼料で飼育し、グループ2は、カプサイシン摂取量が1mg/kg体重/dayとなるよう調製した飼料で飼育した。グループ3は、イソフラボンとカプサイシンの両方の投与を行い、グループ4は、対照群とした。   By the way, from 28 days before endotoxin administration, group 1 out of the above 4 groups was bred with a feed supplemented with soybean germ extract (Fujiflavone P40) so that the amount of isoflavone was 90 mg / kg body weight / day. Were fed with a feed prepared so that the capsaicin intake was 1 mg / kg body weight / day. Group 3 received both isoflavone and capsaicin, and group 4 served as a control group.

そして、上記のようにして測定を行った結果、グループ1、2はグループ4と比較して血圧の低下がやや抑えられた。これに対して、グループ3は、著明な血圧低下抑制効果が認められた。また、カルシトニン遺伝子関連ペプチドの量も他グループよりも明らかに高い値を示した。これにより、イソフラボンとカプサイシンを同時に投与することは、カルシトニン遺伝子関連ペプチドの産生を促進し、感染に対する過剰な生体侵襲反応が抑えられたことがわかる。   And as a result of measuring as mentioned above, compared with the group 4, the fall of the blood pressure of the groups 1 and 2 was suppressed a little. On the other hand, Group 3 showed a remarkable blood pressure lowering suppressing effect. The amount of calcitonin gene-related peptide was also clearly higher than other groups. Thus, it can be seen that simultaneous administration of isoflavone and capsaicin promoted the production of calcitonin gene-related peptide and suppressed the excessive bioinvasive reaction to infection.

〔イソフラボンとカプサイシンによる毛包中のカルシトニン遺伝子関連ペプチドおよびインスリン様成長因子の産生促進作用と育毛効果の検定〕
3週齢で購入したC3H/He系マウスを、ランダムに1グループ10匹とし4グループに分け、1週間の馴化飼育後、グループ1はイソフラボンの摂取量が90mg/kg体重/dayとなるように大豆胚芽抽出物(フジフラボンP40)を添加した飼料で飼育し、グループ2は、カプサイシンの摂取量が2mg/kg体重/dayとなるよう調製した飼料で飼育した。グループ3は、イソフラボンとカプサイシンの両方の投与を行い、グループ4は、対照群とした。そして、6週齢で毛刈りを行い、その後の発毛の状況を観察した。すなわち、試験飼料の摂取開始後40日以内に毛の再生が完了したマウスの数の測定を行った。この結果を、下記の表5に示す。
[Improvement of calcitonin gene-related peptide and insulin-like growth factor in hair follicles by isoflavones and capsaicin and assay of hair-growth effect]
C3H / He mice purchased at 3 weeks of age were randomly divided into 4 groups of 10 mice per group, and after 1 week of acclimatization, group 1 had an isoflavone intake of 90 mg / kg body weight / day. The group 2 was reared with a feed supplemented with soybean germ extract (Fujiflavone P40), and the group 2 was reared with a feed prepared so that the capsaicin intake was 2 mg / kg body weight / day. Group 3 received both isoflavone and capsaicin, and group 4 served as a control group. Then, the hair was cut at 6 weeks of age, and the subsequent hair growth was observed. That is, the number of mice whose hair regeneration was completed within 40 days after the start of intake of the test feed was measured. The results are shown in Table 5 below.

上記表5の結果より、イソフラボンとカプサイシンを同時に摂取することにより、著明な育毛効果のあることが認められた。また、毛包中のカルシトニン遺伝子関連ペプチドおよびインスリン様成長因子の量を測定した結果、イソフラボンとカプサイシンを同時に与えたグループ3がグループ1、2、4と比較して有意に多いことがわかった。   From the results of Table 5 above, it was confirmed that there was a significant hair-growth effect by simultaneously taking isoflavones and capsaicin. In addition, as a result of measuring the amounts of calcitonin gene-related peptide and insulin-like growth factor in the hair follicle, it was found that group 3 to which isoflavone and capsaicin were simultaneously given was significantly more than groups 1, 2, and 4.

本発明の、イソフラボンとカプサイシンを必須成分とする可食性組成物は、社会的心理的、あるいは身体的ストレスによって亢進する、TNF−αなどの炎症性サイトカインの産生を抑える働きとインスリン様成長因子を誘導する働きを持つカルシトニン遺伝子関連ペプチドの産生を促進することにより、胃粘膜傷害、生活習慣病、肥満、悪性腫瘍の発生予防及び再発予防効果、骨粗鬆症を予防及び治療する効果を持ち、臓器移植後の拒絶反応の軽減、感染,手術,外傷後の侵襲反応による臓器障害の予防および治療効果、さらには頭髪等の育毛効果を有する。また、作用が穏やかで、副作用がなく、安全性が高い。このような本発明の可食性組成物は、現代の生活において問題となる疾病の予防や治療、あるいは身体的コンプレックスの克服を図る上で、大きく役に立つことが期待される。   The edible composition comprising isoflavones and capsaicin as essential components of the present invention has an action to suppress the production of inflammatory cytokines such as TNF-α, which is enhanced by social psychological or physical stress, and an insulin-like growth factor. By promoting the production of calcitonin gene-related peptide that induces gastric mucosa injury, lifestyle-related diseases, obesity, prevention of malignant tumor occurrence and recurrence prevention, osteoporosis prevention and treatment, after organ transplantation It has the effect of reducing the rejection reaction, prevention and treatment of organ damage due to invasive reaction after infection, surgery, and trauma, and also the effect of hair growth such as hair. In addition, it is mild in action, has no side effects and is highly safe. Such an edible composition of the present invention is expected to be of great use in preventing or treating diseases that are problematic in modern life, or overcoming physical complexities.

Claims (11)

イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有することを特徴とする可食性組成物。   An edible composition comprising isoflavones and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action. イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有することを特徴とする、胃粘膜傷害予防及び治療用可食性組成物。   An edible composition for preventing and treating gastric mucosal injury, comprising isoflavones and capsaicin as essential components and having calcitonin gene-related peptide production and release promoting action. イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有することを特徴とする、生活習慣病予防及び治療用可食性組成物。   An edible composition for the prevention and treatment of lifestyle-related diseases, characterized by comprising isoflavones and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action. イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有することを特徴とする、肥満予防及び治療用可食性組成物。   An edible composition for the prevention and treatment of obesity, comprising isoflavones and capsaicin as essential components and having calcitonin gene-related peptide production and release promoting action. イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有することを特徴とする、悪性腫瘍発生予防,再発予防及び治療用可食性組成物。   An edible composition for malignant tumor prevention, recurrence prevention and treatment, characterized by having isoflavones and capsaicin as essential components, and having calcitonin gene-related peptide production and release promoting action. イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有することを特徴とする、骨粗鬆症予防及び治療用可食性組成物。   An edible composition for the prevention and treatment of osteoporosis, comprising isoflavones and capsaicin as essential components, and having a calcitonin gene-related peptide production and release promoting action. イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有することを特徴とする、臓器移植拒絶反応軽減用可食性組成物。   An edible composition for reducing organ transplant rejection, characterized by comprising isoflavones and capsaicin as essential components and having calcitonin gene-related peptide production and release promoting action. イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有することを特徴とする、感染,外傷,手術等の侵襲要因に対する生体侵襲反応に伴う臓器障害の予防及び軽減用可食性組成物。   An edible composition for the prevention and reduction of organ damage associated with biologically invasive responses to invasive factors such as infection, trauma, and surgery, characterized by isoflavones and capsaicin as essential components, and has a calcitonin gene-related peptide production and release promoting action Stuff. イソフラボンとカプサイシンを必須成分とし、カルシトニン遺伝子関連ペプチド産生および放出促進作用を有することを特徴とする、育毛用可食性組成物。   An edible composition for hair growth, comprising isoflavones and capsaicin as essential components and having a calcitonin gene-related peptide production and release promoting action. イソフラボンが、大豆由来のイソフラボンである請求項1〜9のいずれか一項に記載の可食性組成物。   The edible composition according to any one of claims 1 to 9, wherein the isoflavone is soybean-derived isoflavone. カプサイシンが、唐辛子由来のカプサイシンである請求項1〜10のいずれか一項に記載の可食性組成物。   The edible composition according to any one of claims 1 to 10, wherein the capsaicin is chili-derived capsaicin.
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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005099686A1 (en) * 2004-04-07 2005-10-27 Fujicco Co., Ltd. Edible composition having effects of promoting the production and release of calcitonin gene-related peptide
JP2006151971A (en) * 2004-11-05 2006-06-15 Maruishi Pharmaceutical Co Ltd Insulin-like growth factor-1 secretion promoter
JP2007291014A (en) * 2006-04-25 2007-11-08 Kenji Okajima Edible composition having effect of promoting production and release of calcitonin gene-associated peptide
JP2007314438A (en) * 2006-05-24 2007-12-06 Daicho Kikaku:Kk Antiobestic medicine
JP2009112804A (en) * 2007-10-18 2009-05-28 Minato Ikagaku Kk Blue light stimulation device for promoting internal production of igf-1, and method thereof
JPWO2010074163A1 (en) * 2008-12-24 2012-06-21 ハウス食品株式会社 Composite and production method thereof
JP2013079215A (en) * 2011-10-04 2013-05-02 Nihon Univ Invasion inhibitor for oral cancer cell
JP2019011278A (en) * 2017-06-30 2019-01-24 研二 岡嶋 Edible composition for hair restoration
JP2019011370A (en) * 2018-10-24 2019-01-24 株式会社ダイセル Methods for producing equol-containing compositions
JP2021035350A (en) * 2019-08-21 2021-03-04 国安 王 Food product for stimulating bone strengthening, periosteal repair, fracture healing and hair blackening
JP2022132404A (en) * 2021-12-07 2022-09-08 株式会社ダイセル Method for producing equol-containing composition
JP2023105251A (en) * 2022-07-13 2023-07-28 株式会社ダイセル Methods for producing equol-containing compositions

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005099686A1 (en) * 2004-04-07 2005-10-27 Fujicco Co., Ltd. Edible composition having effects of promoting the production and release of calcitonin gene-related peptide
JP2006151971A (en) * 2004-11-05 2006-06-15 Maruishi Pharmaceutical Co Ltd Insulin-like growth factor-1 secretion promoter
JP2007291014A (en) * 2006-04-25 2007-11-08 Kenji Okajima Edible composition having effect of promoting production and release of calcitonin gene-associated peptide
JP2007314438A (en) * 2006-05-24 2007-12-06 Daicho Kikaku:Kk Antiobestic medicine
JP2009112804A (en) * 2007-10-18 2009-05-28 Minato Ikagaku Kk Blue light stimulation device for promoting internal production of igf-1, and method thereof
JPWO2010074163A1 (en) * 2008-12-24 2012-06-21 ハウス食品株式会社 Composite and production method thereof
JP2013079215A (en) * 2011-10-04 2013-05-02 Nihon Univ Invasion inhibitor for oral cancer cell
JP2019011278A (en) * 2017-06-30 2019-01-24 研二 岡嶋 Edible composition for hair restoration
JP2019011370A (en) * 2018-10-24 2019-01-24 株式会社ダイセル Methods for producing equol-containing compositions
JP2021035350A (en) * 2019-08-21 2021-03-04 国安 王 Food product for stimulating bone strengthening, periosteal repair, fracture healing and hair blackening
JP2022132404A (en) * 2021-12-07 2022-09-08 株式会社ダイセル Method for producing equol-containing composition
JP2023105251A (en) * 2022-07-13 2023-07-28 株式会社ダイセル Methods for producing equol-containing compositions

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