JP2005289839A - Life prolonging agent and use thereof - Google Patents
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本発明は特定なキトサンを有効成分とする寿命延長性剤およびその用途に関する。 The present invention relates to a life extension agent containing a specific chitosan as an active ingredient and use thereof.
わが国は、世界でも有数の長寿国である。一方、ＷＨＯによると発展途上国に住む３０％の人が貧困と飢餓に苦しんでおり、それに起因する栄養欠乏により毎年１１００万人以上の５歳未満の子供が死亡しているといわれている。健康への国民の関心が高まり、健康増進法の施行に伴い、２１世紀における国民健康づくり施策が地方でも積極的に行われるようになってきた。しかし、日本は長寿国にはなったものの運動量が減り、いわゆる生活習慣病は増加の傾向をたどっている。国民の食への関心が高まり、食品の持つ機能成分の研究も盛んに進められるようになってきた。
食や生活習慣の改善で健康を維持できれば今日問題となっている医療費の抑制にもつながるため、今後ますます食品の持つ機能性に関する研究が進行していくものと考えられる。近年、サプリメントとしてキトサンの使用が増加しつつある。
Japan is one of the longest-lived countries in the world. On the other hand, according to WHO, 30% of people living in developing countries suffer from poverty and hunger, and more than 11 million children under the age of 5 die each year due to nutritional deficiencies. As the public's interest in health increases, the health promotion measures in the 21st century have been actively carried out in the local areas as the Health Promotion Act has been enforced. However, although Japan has become a longevity country, the amount of exercise has decreased, and so-called lifestyle-related diseases have been increasing. The public's interest in food has increased, and research into the functional ingredients of food has been actively promoted.
If health can be maintained by improving food and lifestyle habits, it will lead to curtailment of medical expenses, which is a problem today, so it is thought that research on the functionality of food will continue to progress. In recent years, the use of chitosan as a supplement has been increasing.
キチンは、カニ、エビなどの甲殻類、トンボ、セミなど昆虫の外郭成分、あるいはキノコや細胞の細胞壁などに含まれており、地球上ではセルロースに次いで多量に生産されているが、そのほとんどは廃棄されている。資源の枯渇化が叫ばれる中、地球上に残された最後の未利用生物資源（バイオマス）として近年、キチンおよびその誘導体であるキトサンの利用研究が大きく進展してきている。キチンは、Ｎ−アセチルグルコサミンと呼ばれる基が多数結合した多糖類で、生体の支持や防護の役目を持っているために物理・化学的にも強固で、水、酸、アルカリに不溶である。キチンは、生体内ではタンパク質や炭酸カルシウムなどとともに存在しているが、希酸や希アルカリでこれらを除き、さらに強アルカリでアセチル基を取り除いたのがキトサンである。 Chitin is contained in crustaceans such as crabs and shrimp, shells of insects such as dragonflies and cicada, or cell walls of mushrooms and cells, and is produced in large quantities on earth after cellulose. It has been discarded. In recent years, research on the use of chitin and its derivative chitosan has made great progress as the last unused bioresource (biomass) left on the earth, while the depletion of resources has been called out. Chitin is a polysaccharide in which a number of groups called N-acetylglucosamine are bonded, and is physically and chemically strong because it has a role of supporting and protecting the living body, and is insoluble in water, acid and alkali. Chitin exists in vivo with proteins and calcium carbonate, but chitosan is obtained by removing these with dilute acid or dilute alkali and further removing acetyl group with strong alkali.
キトサンは、遊離アミノ基を含む数少ない塩基性の多糖で、構造はセルロースによく似ている。セルロースを植物性の食物繊維とすると、キトサンは動物性の食物繊維で、食品添加物や栄養補助食品として広汎に利用されている。キトサンのマウス、ラットにおける半致死量（ＬＤ50）は、１．５ｇ／ｋｇ以上で、この値はショ糖よりも大きい。これまでの報告では、変異原性、急性毒性、亜急性毒性、慢性毒性、発熱性、溶血性の各試験を行なった結果では、いずれも異常は認められていない。 Chitosan is one of the few basic polysaccharides containing a free amino group, and its structure is very similar to cellulose. When cellulose is used as vegetable dietary fiber, chitosan is an animal dietary fiber and is widely used as a food additive or dietary supplement. The half-lethal dose (LD 50 ) in mice and rats of chitosan is 1.5 g / kg or more, which is larger than that of sucrose. In previous reports, no abnormalities were found in the results of mutagenicity, acute toxicity, subacute toxicity, chronic toxicity, pyrogenicity, and hemolytic properties.
キチン・キトサンは、（１）生体適合性に優れていること、（２）防菌、防黴効果があること、（３）保湿性に優れていること、（４）キレート作用があること、などから医学、理学、農学、工学、薬学など広い範囲で応用研究が行われており、人工皮膚、化粧品、カラム充填剤など商品化されているものも多い。
本発明者らは、キトサンのキレート作用に着目し、放射性物質の吸着や排泄促進剤としての応用研究を行ってきた。これまでの研究により、キトサンが放射性ストロンチウム、放射性亜鉛、放射性鉄に対して排泄促進効果があること、インビトロにおいては放射性コバルト、放射性ルテニウムなどを効率よく吸着し、吸着剤として有用であることを実験的に示し、これらの結果は国内外の学会や学会誌に発表した。また、近年、キトサンを添加した飼料で約１ヶ月飼育したマウスにＸ線を照射すると、マウスが放射線抵抗性を示すことを明らかにした。
Chitin / chitosan has (1) excellent biocompatibility, (2) antibacterial and antifungal effects, (3) excellent moisture retention, (4) chelate action, Applied research is being carried out in a wide range of fields such as medicine, science, agriculture, engineering, pharmacy, etc., and many products such as artificial skin, cosmetics, and column fillers have been commercialized.
The present inventors have paid attention to the chelating action of chitosan and have conducted applied research as a radioactive substance adsorption or excretion promoter. Based on previous research, chitosan has been shown to be effective in promoting excretion of radioactive strontium, radioactive zinc and radioactive iron, and in vitro it can effectively adsorb radioactive cobalt, radioactive ruthenium, etc. and is useful as an adsorbent. These results are presented in national and international academic societies and journals. In recent years, it has been clarified that, when X-rays are irradiated to a mouse raised for about 1 month on a diet supplemented with chitosan, the mouse exhibits radiation resistance.
放射線による障害は、放射線の電離作用に起因する。放射線は、微量でもＤＮＡを傷つけるが、生体にはこれを修復する機能が備わっている。しかし、大量の放射線による被ばくなど、何らかの原因で傷ついたＤＮＡが修復できなくなったときに、細胞死や突然変異を起こしいろいろな障害が出てきて重篤な場合には死を招く。一般に、放射線抵抗性は、抗酸化作用による活性酸素の抑制および免疫機能の活性化によって生ずるものと考えられている。生体成分の約７０％は水から構成されるが、水に放射線が当たるとフリーラジカルが発生する。放射線の生体に対する作用の多くは生体中の水の放射線分解によって生成する活性酸素やフリーラジカルによるものである。水の放射線照射により、スーパーオキシドアニオンラジカル（Ｏ2 -）とヒドロキシラジカル（・ＯＨ）という二つのフリーラジカルが生成するが、生体には活性酸素やフリーラジカルを消去し、生体膜の過酸化を防ぐ強力な化学的防御機構が存在する。このフリーラジカルを消去することが生命維持に不可欠であり、ある種の線虫類ではフリーラジカルを消去することの結果として寿命延長につながるものと推測されている（非特許文献１）。キトサンはヒドロキシラジカルのラジカルスカベンジャーであり、これが放射線抵抗性に関与しているものと考えられるが、今後の詳細な研究が必要である。 Radiation damage is due to the ionizing action of radiation. Radiation damages DNA even in trace amounts, but the living body has a function to repair it. However, when DNA damaged for some reason, such as exposure to a large amount of radiation, can no longer be repaired, cell death or mutation occurs, leading to death in various serious cases. In general, radiation resistance is considered to be caused by suppression of active oxygen by an antioxidant action and activation of immune function. About 70% of the biological components are composed of water, but free radicals are generated when radiation hits the water. Many of the effects of radiation on living bodies are due to active oxygen and free radicals generated by radiolysis of water in the living body. By irradiation of the water, superoxide anion radicals (O 2 -), but the two free radicals of hydroxy radicals (· OH) is generated, the biological erase active oxygen and free radicals, peroxidation of biological membranes There is a strong chemical defense mechanism to prevent. It is presumed that eliminating these free radicals is indispensable for life support, and that in some nematodes, the lifetime is extended as a result of eliminating the free radicals (Non-patent Document 1). Chitosan is a radical scavenger of hydroxy radicals, which are thought to be involved in radiation resistance, but further research is needed in the future.
このように、キトサンの持つ多機能性は数多く知られるようになってきたが、キトサンを長期摂取した場合の生体影響については十分に研究されていない。キトサンに毒性がないことはすでに多くの研究者によって明らかにされているが、長期摂取した場合の生体側の反応についてはほとんど知られていない。放射性物質が体内に摂取されたときに起きる内部被ばくが長期間にわたる場合は排泄促進剤の投与も長期にわたる可能性があるため、安全性はもちろんのこと、生体側の反応を理解しておくことが必要である。われわれはこの研究（マウスによる実験）を行う中でキトサンの寿命延長効果を見出し、本発明に至った。キトサンを長期摂取させることによる毒性試験データは散見するが、終生飼育を行って死亡率を観察した例はこれまでにない。
本発明の目的は、寿命延長効果のある物質を提供することである。
As described above, many multifunctional properties of chitosan have been known, but the biological effects of long-term ingestion of chitosan have not been sufficiently studied. Although many researchers have already shown that chitosan is not toxic, little is known about the reactions on the living body when ingested for a long time. If the internal exposure that occurs when a radioactive substance is ingested into the body for a long period of time, the administration of an excretion enhancer may also be prolonged, so it is important to understand the reaction on the living body as well as safety is required. In conducting this study (experiment with mice), we found a life extension effect of chitosan and reached the present invention. Toxicity test data from long-term ingestion of chitosan are scattered, but there has never been a case where mortality was observed through lifelong breeding.
An object of the present invention is to provide a substance having a life extension effect.
本発明によれば、脱アセチル化度が７０〜１００モル％、重量平均分子量が、５，０００〜１，０００，０００であるキトサンを有効成分とすることを特徴とする寿命延長性剤が提供される。 According to the present invention, there is provided a life prolonging agent characterized in that chitosan having a deacetylation degree of 70 to 100 mol% and a weight average molecular weight of 5,000 to 1,000,000 is an active ingredient. Is done.
キチン・キトサンは、高尿酸値血症予防や血糖値上昇抑制効果が期待できるため特定健康食品としての利用研究が盛んに行われているが、これらの機能に寿命延長効果が加わることでキチン・キトサンの利用に拍車をかけることが予想されるとともに、健康で長生きするための補助食品として利用されることが期待され、高齢化社会を迎えたわが国での高額医療費の抑制につながるものと考えられる。更に、医薬品用添加剤、通常の食品添加剤として、また、動物用飼料の添加剤としても利用が期待される。 Chitin / chitosan has been actively studied for its use as a specific health food because it can be expected to prevent hyperuricemia and suppress blood glucose level rise. It is expected to spur the use of chitosan, and it is expected to be used as a supplement for healthy and long-lived life. It is done. Further, it is expected to be used as a pharmaceutical additive, a normal food additive, and an animal feed additive.
以下に発明を実施するための最良の形態を挙げて本発明を詳細に説明する。
本発明の寿命延長性剤として使用するキトサンは、脱アセチル化度が７０〜１００モル％、好ましくは８０〜９０モル％で、重量平均分子量（ＧＰＣ、プルラン換算）が５，０００〜１，０００，０００、好ましくは１０，０００〜１００，０００の範囲のものである。
BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below with reference to the best mode for carrying out the invention.
The chitosan used as the life extension agent of the present invention has a deacetylation degree of 70 to 100 mol%, preferably 80 to 90 mol%, and a weight average molecular weight (GPC, pullulan conversion) of 5,000 to 1,000. , Preferably 10,000 to 100,000.
本発明の寿命延長性剤は、それ自体を服用することもできるが、食品、動物用飼料および医薬品に添加して使用される。即ち、「剤」は「添加剤」を意味する。
本発明の寿命延長性剤を食品用添加剤として使用する場合、食品は特に限定されず、一般の食品および健康食品が対象である。一般食品としては、例えば、飲料、味噌、めん類、蒲鉾などの練り製品、菓子類、ソーセイジ類などが挙げられる。健康食品としては、例えば、各種ビタミン類との混合物（錠剤）、各種ミネラルとの混合物（錠剤）などのサプリメント類、粉末状スポーツドリンク（水に溶解して（キトサンは分散させて）使用）などが挙げられる。上記キトサンの添加量は、特に制限されないが、通常、食品の質量に対して０．１〜３０質量％程度である。また、キトサンの粉末度は、通常、４０〜２００メッシュパス程度である。上記キトサンの摂取量は、人の体重によって異なり、特に制限されないが、キトサンは食物繊維であることから多く摂取しても実害はない。コストを考慮すれば、例えば、０．５〜５０ｇ／日程度である。寿命延長効果は、寿命延長性剤が配合された食品を毎日、あるいは断続的であっても、長期にわたって、例えば、年単位で摂取することが好ましい。
The life prolonging agent of the present invention can be taken by itself, but is added to foods, animal feeds and pharmaceuticals. That is, “agent” means “additive”.
When the life extending agent of the present invention is used as a food additive, the food is not particularly limited, and includes general foods and health foods. Examples of the general food include kneaded products such as beverages, miso, noodles, and koji, confectionery, and sausages. Examples of health foods include supplements such as mixtures with various vitamins (tablets), mixtures with various minerals (tablets), powdered sports drinks (dissolved in water (chitosan dispersed)), etc. Is mentioned. The amount of chitosan added is not particularly limited, but is usually about 0.1 to 30% by mass with respect to the mass of the food. Moreover, the fineness of chitosan is usually about 40 to 200 mesh pass. The intake of chitosan varies depending on the weight of the person and is not particularly limited. However, since chitosan is a dietary fiber, there is no harm even if it is consumed in large quantities. Considering the cost, for example, it is about 0.5 to 50 g / day. As for the life extension effect, it is preferable to take a food containing a life extension agent daily or intermittently over a long period, for example, in units of years.
本発明の寿命延長性剤を動物用飼料の添加剤として使用する場合、動物用飼料自体は、限定されず、動物用であればいずれでもよい。対象の動物も特に制限されず、例えば、牛、馬などの大型動物、犬、猫などのペット類、鰻などの養殖魚類などが挙げられる。上記キトサンの家畜用飼料に対する配合量は、特に制限されないが、通常、０．０１〜１０質量％程度である。少な過ぎると延命効果が得られ難く、多過ぎると配合量に見合った寿命延長効果は得られず、不経済である。上記キトサンは、通常、４０〜２００メッシュパス程度の粉末として動物用飼料に配合される。上記キトサンの摂取量は、動物の体重によって異なり、特に制限されないが、キトサンは食物繊維であることから多く摂取しても実害はない。コストを考慮すれば、例えば、０．５〜５００ｇ／日程度である。寿命延長効果は、寿命延長性剤が配合された飼料を毎日、あるいは断続的であっても、長期にわたって、例えば、年単位で摂取することが必要である。 When the life extending agent of the present invention is used as an additive for animal feed, the animal feed itself is not limited and any animal feed may be used. The target animal is not particularly limited, and examples thereof include large animals such as cattle and horses, pets such as dogs and cats, and cultured fish such as salmon. Although the compounding quantity with respect to the feed for livestock of the said chitosan is not restrict | limited, Usually, it is about 0.01-10 mass%. If the amount is too small, it is difficult to obtain a life extension effect. If the amount is too large, a life extension effect corresponding to the blending amount cannot be obtained, which is uneconomical. The chitosan is usually blended in animal feed as a powder of about 40 to 200 mesh pass. The intake of chitosan varies depending on the body weight of the animal and is not particularly limited. However, since chitosan is a dietary fiber, there is no harm even if it is consumed in large quantities. Considering the cost, for example, it is about 0.5 to 500 g / day. The life extension effect requires that a feed containing a life extension agent is ingested daily or intermittently over a long period of time, for example, yearly.
本発明の寿命延長性剤を医薬品用の添加剤として使用する場合、粉末、錠剤、あるいは顆粒の形態の医薬品に混合して用いることができる。上記の形態を有する医薬品であれば医薬品の種類は特に制限されない。添加量も特に制限されず、通常、医薬品の質量に対して０．０１〜１０質量％程度である。また、キトサンの粉末度は、通常、４０〜２００メッシュパス程度である。 When the life extending agent of the present invention is used as an additive for pharmaceuticals, it can be used by mixing with pharmaceuticals in the form of powder, tablets, or granules. If it is a pharmaceutical which has said form, the kind of pharmaceutical will not be restrict | limited in particular. The addition amount is not particularly limited, and is usually about 0.01 to 10% by mass with respect to the mass of the pharmaceutical product. Moreover, the fineness of chitosan is usually about 40 to 200 mesh pass.
以下に実施例および比較例を挙げて本発明を更に具体的に説明する。 Hereinafter, the present invention will be described more specifically with reference to examples and comparative examples.
実施例１、比較例１
実験には６週齢のフィッシャー３４４（Ｆ−３４４／ＤｕＣｒｊ）雌ラット（日本チャールスリバー株式会社より購入）１００匹を使用した。ラットは５０匹ずつ２群に分け、一群にはオリエンタル酵母株式会社製のマウス・ラット用育成用固形飼料（オリエンタル−ＭＦ）を、一群には上記飼料に対して５質量％のキトサン（脱アセチル化度８５モル％；重量平均分子量約５０，０００）粉末を添加した固形飼料を作成して与え、終生飼育を行った。
Example 1 and Comparative Example 1
In the experiment, 100 6-week-old Fischer 344 (F-344 / DuCrj) female rats (purchased from Japan Charles River Co., Ltd.) were used. Rats were divided into two groups of 50 rats, one group was a solid feed for breeding mice and rats (Oriental-MF) manufactured by Oriental Yeast Co., Ltd. A solid feed to which powder was added (powdering degree 85 mol%; weight average molecular weight about 50,000) was prepared and given for lifelong breeding.
ラットは、室温（２５℃）、湿度約７０％にコントロールされた動物飼育室で飼育し、両群とも餌と水は自由に摂取させた。飼育期間中、随時体重を測定するとともに、死亡後の病理標本をランダムに作製した。ラットの平均寿命は２〜３年といわれているが、系統や飼育施設などの環境により若干異なる。今回の実験において飼育後からの平均生存日数を比べると対照群で８６７日、キトサン摂取群では９０４日とキトサン摂取群で３７日の寿命延長が認められた。終生飼育したときの生存曲線と体重変化を、それぞれ図１および図２に示す。飼育後からの平均生存日数はコントロール食（通常食）で８６７±１６．８日、キトサン食で９０４±２２．８日であった。Ｌｏｇ−Ｒａｎｋ検定を行うと０．３％の危険率で有意に寿命延長が認められた。 Rats were raised in an animal room controlled at room temperature (25 ° C.) and humidity of about 70%, and food and water were freely consumed in both groups. During the breeding period, body weight was measured at any time and pathological specimens after death were randomly prepared. The average life span of rats is said to be 2 to 3 years, but varies slightly depending on the environment such as strain and breeding facilities. In this experiment, the life expectancy after breeding was compared, 867 days in the control group, 904 days in the chitosan-ingested group and 37 days in the chitosan-ingested group. The survival curves and changes in body weight when reared for life are shown in FIGS. 1 and 2, respectively. Average survival days after breeding were 867 ± 16.8 days for the control diet (normal diet) and 904 ± 22.8 days for the chitosan diet. When the Log-Rank test was performed, the life expectancy was significantly increased at a risk rate of 0.3%.
一概に動物のライフスパンを人に当てはめることができないが、キトサンを摂取することで平均寿命を約４％延長させたことになる。この理由は明らかではないが、キトサンがヒドロキシラジカルのラジカルスカベンジャーであることや、キトサンの持つ免疫賦活能が関与しているものと考えられる。従って、動物用飼料に添加し、日常的に摂取することで寿命延長効果が期待できる。人に対しても、サプリメントなどとして日常的に摂取することにより、寿命延長効果が期待できる。 In general, the life span of animals cannot be applied to humans, but taking the chitosan extended the average life span by about 4%. The reason for this is not clear, but it is thought that chitosan is a radical scavenger of hydroxy radicals and that the immunostimulatory ability of chitosan is involved. Therefore, a life extension effect can be expected by adding it to animal feed and ingesting it daily. Life expectancy can be expected for humans by taking it daily as a supplement.
病理所見においては、加齢によるものと思われる病理変化は認められたが、両群の間で差は認められなかった。また、体重変化に差は認められなかった。これらの結果は、キトサンを終生摂取しても身体に大きな影響を及ぼさないことを示唆しており、食品中に添加しても安全なことを示しているといえる。 The pathological findings showed pathological changes that seemed to be due to aging, but there was no difference between the two groups. There was no difference in weight change. These results suggest that even if chitosan is consumed throughout life, it does not have a significant effect on the body, and it can be said that it is safe to add to foods.
前記キトサンの寿命延長効果は、人間を含めた動物に対しても期待できるものである。キチン・キトサンは、高尿酸値血症予防や血糖値上昇抑制効果が期待できるため特定健康食品としての利用研究が盛んに行われているが、これらの機能に寿命延長効果が加わることでキチン・キトサンの利用に拍車をかけることが予想されるとともに、健康で長生きするための補助食品、医薬品用添加剤として利用されることが期待され、高齢化社会を迎えたわが国での高額医療費の抑制につながるものと考えられる。また、動物に対しては、飼料用添加剤としての利用が期待される。 The effect of extending the life of chitosan can be expected for animals including humans. Chitin / chitosan has been actively studied for its use as a specific health food because it can be expected to prevent hyperuricemia and suppress blood glucose level rise. It is expected to spur the use of chitosan, and it is expected to be used as a supplement and a pharmaceutical additive for a healthy and long-lived life. It is thought that it leads to. For animals, it is expected to be used as a feed additive.
Claims (4)
A pharmaceutical product to which the life prolonging agent according to claim 1 is added.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP2537422A1 (en) | 2011-06-24 | 2012-12-26 | National University Corporation Kagawa University | Lifespan extending agent |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08112077A (en) * | 1994-10-14 | 1996-05-07 | Daiwa Kasei Kogyo Kk | Mealth food composition consisting of chitosan and gingo leaf extract |
| JPH119196A (en) * | 1997-06-24 | 1999-01-19 | Meiji Seika Kaisha Ltd | Prevention of loss in livestock with chitosan |
| JP2002104975A (en) * | 2000-09-29 | 2002-04-10 | Kazuo Sakai | Anorectic agent |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08112077A (en) * | 1994-10-14 | 1996-05-07 | Daiwa Kasei Kogyo Kk | Mealth food composition consisting of chitosan and gingo leaf extract |
| JPH119196A (en) * | 1997-06-24 | 1999-01-19 | Meiji Seika Kaisha Ltd | Prevention of loss in livestock with chitosan |
| JP2002104975A (en) * | 2000-09-29 | 2002-04-10 | Kazuo Sakai | Anorectic agent |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP2537422A1 (en) | 2011-06-24 | 2012-12-26 | National University Corporation Kagawa University | Lifespan extending agent |
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