JP2006273762A - Uricosuric agent - Google Patents
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- JP2006273762A JP2006273762A JP2005096614A JP2005096614A JP2006273762A JP 2006273762 A JP2006273762 A JP 2006273762A JP 2005096614 A JP2005096614 A JP 2005096614A JP 2005096614 A JP2005096614 A JP 2005096614A JP 2006273762 A JP2006273762 A JP 2006273762A
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Abstract
Description
本発明は、新規な尿酸排泄促進剤及びそれを含有する飲食品、医薬品又は化粧品に関する。 The present invention relates to a novel uric acid excretion promoter and a food, drink, pharmaceutical or cosmetic containing the same.
痛風は、プリン体の代謝異常による高尿酸血症を基礎とし、関節内又は関節周囲に尿酸塩の結晶が沈着して痛風結節、関節機能障害、関節の変形などが生じる疾患であり、腎障害、血管障害など、多くの合併症を引き起こす病気である。食餌によるプリン体過剰摂取、体内で尿酸合成促進、あるいは、尿中への尿酸排泄が阻害されると血中尿酸値は上昇する。そこで、消化管におけるプリン体吸収阻害、尿酸合成抑制、尿酸排泄促進することにより血中尿酸レベルを改善することができると考えられる。
近年の生活様式の急速な変化にともない、痛風の発症事例は増えている。このため、痛風あるいはそのリスクファクターである高尿酸血症の予防と治療に対する関心が高まっている。
高尿酸血症の是正には尿酸生成阻害剤つまりキサンチンオキシダーゼ阻害剤が有用である。エラグ酸及びエラグ酸誘導体が、キサンチンオキシダーゼ阻害剤として公知である（特許文献１）。また、尿酸排泄促進剤も、血中尿酸値低下剤、高尿酸血症の予防又は改善剤、痛風の予防剤として有用であると考えられる。医薬品ではベンズブロマロンが公知である。
Gout is a disease based on hyperuricemia caused by abnormal metabolism of purines, causing the formation of gouty nodules, joint dysfunction, joint deformation, etc. due to the deposition of uric acid crystals in or around the joint. It is a disease that causes many complications, such as vascular disorders. The blood uric acid level rises when excessive purine intake due to diet, promotion of uric acid synthesis in the body, or inhibition of uric acid excretion into the urine is inhibited. Therefore, it is considered that the blood uric acid level can be improved by inhibiting purine body absorption in the digestive tract, suppressing uric acid synthesis, and promoting uric acid excretion.
With the rapid changes in lifestyle in recent years, the incidence of gout has increased. For this reason, there is a growing interest in the prevention and treatment of gout or its risk factor hyperuricemia.
To correct hyperuricemia, a uric acid production inhibitor, that is, a xanthine oxidase inhibitor is useful. Ellagic acid and ellagic acid derivatives are known as xanthine oxidase inhibitors (Patent Document 1). Uric acid excretion promoters are also considered useful as blood uric acid level lowering agents, preventive or ameliorating agents for hyperuricemia, and preventive agents for gout. Benzbromarone is known as a medicine.
本発明の課題は、新規な尿酸排泄促進剤及びそれを含有する飲食品、医薬品又は化粧品を提供することにある。 The subject of this invention is providing the novel uric acid excretion promoter and the food-drinks, pharmaceutical, or cosmetics containing it.
本発明者らは、エラグ酸及びザクロ抽出物が尿酸排泄促進活性を有することを見出し、本発明を完成した。すなわち本発明は、以下に係るものである。
（１）エラグ酸を有効成分とする尿酸排泄促進剤。
（２）ザクロ抽出物を有効成分とする尿酸排泄促進剤。
（３）上記（１）又は（２）記載の尿酸排泄促進剤を含有する、飲食品、医薬品又は化粧品。
（４）エラグ酸又はザクロ抽出物を含有し、尿酸排泄促進のために用いられるものである旨の表示を付した飲食品。
The present inventors have found that ellagic acid and pomegranate extract have uric acid excretion promoting activity, and have completed the present invention. That is, the present invention relates to the following.
(1) A uric acid excretion promoter comprising ellagic acid as an active ingredient.
(2) Uric acid excretion promoter comprising pomegranate extract as an active ingredient.
(3) Food / beverage products, pharmaceuticals or cosmetics containing the uric acid excretion promoter according to (1) or (2) above.
(4) Food / beverage products containing ellagic acid or pomegranate extract and labeled as being used for promoting uric acid excretion.
本発明の有効成分であるエラグ酸及びザクロ抽出物は、尿酸排泄促進作用を有しており、尿酸排泄促進剤として、血中尿酸値低下、高尿酸血症の予防又は改善剤、痛風の予防のために有用である。 The ellagic acid and pomegranate extract, which are the active ingredients of the present invention, have a uric acid excretion promoting action, and as a uric acid excretion promoting agent, blood uric acid level lowering, hyperuricemia prevention or improvement agent, gout prevention Useful for.
１．エラグ酸を有効成分とする尿酸排泄促進剤
本発明における有効成分の１つは「エラグ酸（ellagic acid）」である。実施例に示す通り、エラグ酸は、尿酸の体外への排泄を促進する作用を有する。本発明のエラグ酸とは、エラグ酸又はその誘導体を意味する。エラグ酸誘導体とは、例えば、エラグ酸の基本骨格に糖・脂質・アミノ酸・タンニン等が結合した化合物、エラグ酸の金属塩、エラグ酸のメチル化物あるいはアセチル化物、エラグ酸の配糖体・エステルである。
エラグ酸誘導体の一例は、植物に多く含まれるエラジタンニンである。エラジタンニンを摂取すると生体内の加水分解反応によってエラグ酸を生成する。使用者の生体内における化学反応により、エラグ酸あるいはエラグ酸誘導体を生成可能な化合物（エラグ酸前駆体）も、本発明でいうエラグ酸に含まれる。
エラグ酸は、植物体や微生物体から、当業者に公知の任意の抽出法、発酵法、化学的もしくは酵素的合成法等により得られる。又、市販品を使用しても良い。植物体及び微生物体としては、エラグ酸を含有する限り特に制限はない。植物体とは、例えば、ザクロ、レッドラズベリー、ストロベリー、ウォールナッツ、ピーカン、クランベリーである。植物体は、尿酸排泄促進作用を有する部分であれば、どの部分、例えば、花、実、種子、果実若しくはそれらの果肉又は皮類、及び根、樹木、樹皮、葉などを使用してもよい。それらは乾燥したもの、生のものどちらでもよい。更に、果実のジュース類若しくはリンゴ酒、ブドウ酒などの果実酒、ビール類、又はそれらの製造の際、副産物として生成する粕類、又は植物体の加工物なども挙げられる。植物体や微生物体由来のエラグ酸は、当該原料からの粗精製物であってもよいし、カラムクロマトグラフ等を用いて精製した高純度標品であってもよい。
1. Uric acid excretion promoter containing ellagic acid as an active ingredient One of the active ingredients in the present invention is "ellagic acid". As shown in the Examples, ellagic acid has an action of promoting excretion of uric acid outside the body. The ellagic acid of the present invention means ellagic acid or a derivative thereof. Examples of ellagic acid derivatives include compounds in which sugar, lipid, amino acid, tannin, etc. are bound to the basic skeleton of ellagic acid, metal salts of ellagic acid, methylated or acetylated ellagic acid, and glycosides / esters of ellagic acid It is.
An example of an ellagic acid derivative is ellagitannin, which is abundant in plants. Ingestion of ellagitannin produces ellagic acid by in vivo hydrolysis reaction. A compound (ellagic acid precursor) capable of producing ellagic acid or an ellagic acid derivative by a chemical reaction in a user's living body is also included in the ellagic acid referred to in the present invention.
Ellagic acid can be obtained from a plant or microorganism by any extraction method, fermentation method, chemical or enzymatic synthesis method, etc. known to those skilled in the art. Moreover, you may use a commercial item. The plant body and the microorganism body are not particularly limited as long as they contain ellagic acid. Plants are, for example, pomegranate, red raspberry, strawberry, walnut, pecan, and cranberry. The plant body may be any part as long as it has a uric acid excretion promoting action, such as flowers, fruits, seeds, fruits or their flesh or skin, and roots, trees, bark, leaves, etc. . They can be either dry or raw. In addition, fruit juices such as fruit juices, apple liquor, grape liquor, beer, potatoes produced as a by-product in the production thereof, or processed plant products are also included. The ellagic acid derived from a plant or microorganism may be a crude product from the raw material or a high-purity sample purified using a column chromatograph or the like.
２．ザクロ抽出物を有効成分とする尿酸排泄促進剤
本発明における有効成分の１つはザクロ抽出物である。実施例に示す通り、ザクロ抽出物は、尿酸の体外への排泄を促進する作用を有する。
ザクロ（Punica granatum L.）とはザクロ科ザクロ属の高木性果樹であり、果実は球形で、成熟すると橙紅色から真紅色となる。果実内には多数の種子があり、外種皮の周りに形成される種衣が食用となる。外種皮は淡黄色、黄紅色、真紅色、赤紫色など品種によって異なる。また、ザクロは北アフリカ、ペルシャ地方を原産とし、地中海地方の国々、イラン、アフガニスタン、インド、アメリカ合衆国（カリフォルニア）、中国、日本、ロシアなど広く世界中で栽培されている。ザクロは最も古くから食用として、また、生薬「セキリュウ」として利用されてきている。例えば、ザクロの果皮は収斂，止瀉薬，根皮又は幹皮は有鉤條虫駆除薬にされる。
ザクロ果皮にはタンニンが含まれ、タンニンは加水分解によりエラグ酸を生じる。またザクロ果実は、エラグ酸やアントシアニジンを主とするポリフェノールを含む。
2. Uric acid excretion promoter containing pomegranate extract as an active ingredient One of the active ingredients in the present invention is a pomegranate extract. As shown in the Examples, the pomegranate extract has an action of promoting excretion of uric acid outside the body.
Pomegranate (Punica granatum L.) is a high tree fruit tree belonging to the genus Pomegranate belonging to the family Pomegranate. The fruit has a spherical shape and changes from orange to crimson when mature. There are many seeds in the fruit, and the garments formed around the outer seed coat are edible. The outer seed coat varies depending on the variety such as pale yellow, yellowish red, crimson, reddish purple. Pomegranate is native to North Africa and the Persian region, and is widely cultivated all over the world, including Mediterranean countries, Iran, Afghanistan, India, the United States (California), China, Japan and Russia. Pomegranate has long been used as an edible and herbal medicine “Sekiryu”. For example, the pomegranate peel is astringent, antipruritic, and the root bark or stem skin is used as an insecticide.
Pomegranate peel contains tannin, which produces ellagic acid by hydrolysis. The pomegranate fruit contains polyphenols mainly composed of ellagic acid and anthocyanidins.
本発明のザクロ抽出物は、任意のザクロ品種の果実全体又は果実の外種皮等の適当な部分から、当業者に公知の任意の抽出法により得ることができる。飲料製造等において利用されたザクロ果実を圧搾して果汁を採取した残渣、すなわち搾汁粕を抽出に供してもよい。尚、抽出の出発材料であるザクロ原料ザクロ果実等は、乾燥若しくはそれを粉砕したもの、又は、生のものどちらでもよい。
ザクロの抽出は、例えば、水又は有機溶媒を用いて実施可能である。有機溶媒とは例えば、メタノール、エタノール、イソプロパノール、ｎ−ブタノール等の水溶性アルコール類、アセトン、酢酸等である。水溶性有機溶媒は単独で用いてもよいが、任意の比で水と混合して用いてもよい。毒性が低い、沸点が比較的低いため抽出後の除去が容易、入手容易等の理由から、水溶性有機溶媒としてはエタノールが好ましい。抽出効率を高く、不純物の割合を少なくするためには、エタノール：水の混合比は１：１〜４：１（ｖ／ｖ）が好ましい。
The pomegranate extract of the present invention can be obtained by any extraction method known to those skilled in the art from an appropriate portion such as the whole fruit of an arbitrary pomegranate variety or the outer seed coat of the fruit. You may use for the extraction the residue which extract | collected the pomegranate fruit utilized in drink manufacture etc., and extract | collected fruit juice, ie, a juice lees. The pomegranate raw material pomegranate fruit or the like, which is the starting material for extraction, may be either dried or pulverized, or raw.
The extraction of pomegranate can be performed using, for example, water or an organic solvent. Examples of the organic solvent include water-soluble alcohols such as methanol, ethanol, isopropanol, and n-butanol, acetone, acetic acid, and the like. The water-soluble organic solvent may be used alone, but may be used by mixing with water at an arbitrary ratio. Ethanol is preferred as the water-soluble organic solvent because it has low toxicity and has a relatively low boiling point so that it can be easily removed after extraction and is easily available. In order to increase extraction efficiency and reduce the proportion of impurities, the ethanol: water mixing ratio is preferably 1: 1 to 4: 1 (v / v).
抽出する際のザクロ原料（無水物換算）に対する溶媒の量は特に限定しないが、通常１〜２０倍量（ｖ／ｗ）、好ましくは２〜６倍量である。また必要により少量の界面活性剤（例えばショ糖脂肪酸エステル等）や酸化防止剤（例えばアスコルビン酸等）などを加えてもよい。また必要により、不活性ガス雰囲気下で抽出を行ってもよい。
ザクロ原料の抽出に際しては、還流させながら抽出を行うことが好ましい。抽出時間は、溶媒量、溶媒の種類、温度等の抽出条件に左右されるが、通常１０分〜２４時間であり、好ましくは３０分〜２時間程度である。
Although the quantity of the solvent with respect to the pomegranate raw material (anhydride conversion) at the time of extraction is not specifically limited, Usually, 1-20 times amount (v / w), Preferably it is 2-6 times amount. If necessary, a small amount of a surfactant (such as sucrose fatty acid ester) or an antioxidant (such as ascorbic acid) may be added. If necessary, extraction may be performed in an inert gas atmosphere.
When extracting the pomegranate raw material, it is preferable to perform extraction while refluxing. The extraction time depends on extraction conditions such as the amount of solvent, the type of solvent, and temperature, but is usually 10 minutes to 24 hours, preferably about 30 minutes to 2 hours.
上記方法により得られる粗抽出物は、適宜、濃縮及び／又は乾燥して使用するか、更に、有機溶媒などで抽出した後に、アルカリ溶液を加えて攪拌・濾過などの造作を施して沈殿物を得、これを濃縮及び／又は乾燥したものを使用することが出来る。
粗抽出物を本発明の有効成分であるザクロ抽出物として使用することもできるが、更に、セファデックス、ポリアミド、シリカゲル、ＯＤＳ等を用いたカラムクロマトグラフ、セルロース膜等を用いた膜分離、酢酸エチル−水等を用いた液液分離、酵母等の微生物の添加による不純物の分解など精製・分離・脱色操作を行うことにより、より高純度に有効成分を含有するザクロ抽出物が得られる。なお、本発明のザクロ抽出物は、エラグ酸を含んでいるものが好ましい。
また、本発明のザクロ抽出物としては、市販品、例えば、ザクロ果実外皮又はザクロ果実全体を７０〜８０％エタノールで抽出し、抽出物を濃縮、乾燥したものが使用できる。該抽出物を更にエタノール蒸留して不純物を除去した後、アルカリ溶液を加え攪拌し、濾過して沈殿物を得、これを乾燥して得られた粉末も市販されており、本発明のザクロ抽出物として使用できる。
The crude extract obtained by the above method is used after being concentrated and / or dried as appropriate, or further extracted with an organic solvent, and then added with an alkali solution and subjected to agitation such as stirring and filtration to obtain a precipitate. Obtained and concentrated and / or dried can be used.
The crude extract can be used as a pomegranate extract as an active ingredient of the present invention, but further, column separation using Sephadex, polyamide, silica gel, ODS, etc., membrane separation using cellulose membrane, etc., acetic acid A pomegranate extract containing the active ingredient with higher purity can be obtained by performing purification / separation / decolorization operations such as liquid-liquid separation using ethyl-water or the like, and decomposition of impurities by addition of microorganisms such as yeast. The pomegranate extract of the present invention preferably contains ellagic acid.
Moreover, as a pomegranate extract of the present invention, a commercially available product, for example, a pomegranate fruit hull or a whole pomegranate fruit extracted with 70 to 80% ethanol, and the extract is concentrated and dried can be used. The extract is further distilled by ethanol to remove impurities, and then added with an alkaline solution, stirred, filtered to obtain a precipitate, and dried to obtain a powder, which is also commercially available. Can be used as a thing.
３．尿酸排泄促進剤を含有する飲食品、医薬品又は化粧品
本発明の尿酸排泄促進剤は、飲食品、医薬品又は化粧品に添加して使用できる。飲食品、医薬品又は化粧品の種類、形態、及びその他の含有成分等に特に制約はなく、当業者に公知の任意の各種方法で容易に調製することが出来る。
本発明の飲食品の形態としては、例えば、顆粒状、粒状、ペースト状、ゲル状、固形状、又は、液体状に任意に成形することが出来る。これらには、食品中に含有することが認められている当業者に公知の各種物質、例えば、結合剤、崩壊剤、増粘剤、分散剤、再吸収促進剤、矯味剤、緩衝剤、界面活性剤、溶解補助剤、保存剤、乳化剤、等張化剤、安定化剤やｐＨ調製剤などの賦形剤を適宜含有させることが出来る。
本発明の飲食品に含まれる有効成分の量は、それらの種類、目的、形態、利用方法などに応じて、適宜決めることが出来、例えば、０．０１％〜８０％程度とすることができる。特に、保健用飲食品，機能性食品、又は健康志向食品等として利用する場合には、本発明の有効成分を所定の効果が十分発揮されるような量で含有させることが好ましい。また、本発明の飲食品は、エラグ酸又はザクロ抽出物を含有し、尿酸排泄促進のために用いられるものである旨の表示を付した飲食品とすることができる。
3. Food / beverage products, pharmaceuticals or cosmetics containing uric acid excretion promoters The uric acid excretion promoters of the present invention can be added to foods / beverages, pharmaceuticals or cosmetics. There is no restriction | limiting in particular in the kind of food / beverage products, a pharmaceutical, or cosmetics, a form, and other containing components, It can prepare easily by arbitrary various methods well-known to those skilled in the art.
As a form of the food / beverage products of this invention, it can shape | mold arbitrarily, for example in granular form, a granular form, a paste form, a gel form, solid form, or a liquid form. These include various substances known to those skilled in the art that are known to be contained in foods, such as binders, disintegrants, thickeners, dispersants, reabsorption accelerators, corrigents, buffers, interfaces. Excipients such as activators, solubilizers, preservatives, emulsifiers, tonicity agents, stabilizers and pH adjusters can be included as appropriate.
The amount of the active ingredient contained in the food or drink of the present invention can be determined as appropriate according to the type, purpose, form, method of use, etc., and can be, for example, about 0.01% to 80%. . In particular, when used as a health food or drink, a functional food, a health-oriented food, or the like, it is preferable to contain the active ingredient of the present invention in such an amount that a predetermined effect is sufficiently exhibited. Moreover, the food / beverage products of this invention can be made into the food / beverage products which contained the ellagic acid or the pomegranate extract and attached | subjected the display to the effect of promoting uric acid excretion.
本発明の医薬品は、例えば錠剤、顆粒剤、散剤、カプセル剤などの固形剤、又は、注射剤などの液剤などいずれの形態にも公知の方法により適宜調製することができる。これらの医薬品には通常用いられる結合剤、崩壊剤、増粘剤、分散剤、再吸収促進剤、矯味剤、緩衝剤、界面活性剤、溶解補助剤、保存剤、乳化剤、等張化剤、安定化剤やｐＨ調製剤などの賦形剤を適宜使用してもよい。
本発明の医薬品は、経口的にあるいは非経口的に適宜に使用される。すなわち、経口、静脈、腹腔内の投与などによって所望の効果を表すものである。
本発明の医薬品における有効成分の投与量は、その種類、その剤型、また患者の年令、体重、適応症状などによって異なるが、例えば経口投与の場合は、成人一日１回又は数回投与され、一日当たり約１０ｍｇ〜５ｇ、好ましくは５０ｍｇ〜１ｇ程度投与するのがよい。
本発明の化粧品も、例えば、液体状、ペースト状、又は、ゲル状の任意の形態とすることができる。これらの中にも、化粧品中に含有することが認められている、当業者に公知の各種物質を適宜含有させることが出来る。
以下、実施例にて本発明を具体的に説明するが、本発明の技術的範囲はこれらの記載によって何等制限されるものではない。
The pharmaceutical agent of the present invention can be appropriately prepared by a known method in any form such as a solid agent such as a tablet, granule, powder or capsule, or a liquid agent such as an injection. For these pharmaceuticals, binders, disintegrating agents, thickeners, dispersants, reabsorption accelerators, taste-masking agents, buffers, surfactants, solubilizers, preservatives, emulsifiers, tonicity agents, Excipients such as stabilizers and pH adjusters may be used as appropriate.
The pharmaceutical of the present invention is appropriately used orally or parenterally. That is, a desired effect is expressed by oral, intravenous, intraperitoneal administration or the like.
The dose of the active ingredient in the pharmaceutical product of the present invention varies depending on the type, dosage form, age, weight, indication, etc. of the patient. For example, in the case of oral administration, it is administered once or several times a day for an adult. The daily dose is about 10 mg to 5 g, preferably about 50 mg to 1 g.
The cosmetic of the present invention can also be in any form, for example, liquid, paste, or gel. Among these, various substances known to those skilled in the art that are recognized to be contained in cosmetics can be appropriately contained.
EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples. However, the technical scope of the present invention is not limited to these descriptions.
以下の試験により、エラグ酸及びザクロ抽出物の尿酸排泄促進作用を確認した。 The following tests confirmed the uric acid excretion promoting action of ellagic acid and pomegranate extract.
１．エラグ酸
市販のエラグ酸（和光純薬社製）を用いた。
２．ザクロ抽出物
ザクロ果実外皮をエタノールで抽出し、エタノール蒸留して不純物を除去した後、アルカリ溶液を加え攪拌し、濾過して沈殿物を得た。該沈殿物を乾燥して得られた粉末を本発明のザクロ抽出物とした。該ザクロ抽出物は、エラグ酸を９０％含有する。
３．血清中尿酸値の測定法
血液を採血後３０〜６０分放置した後、１０，０００ｒｐｍで１０分間遠心し血清を、尿は濾紙ろ過後、３，０００ｒｐｍで１０分遠心し上清を得た。血清中尿酸値は、以下の条件でＨＰＬＣにて分析した。
ＨＰＬＣカラムはＷａｋｏｓｉｌ ＧＰ−Ｎ６（１５ｃｍ×４．６ｍｍ Ｉ．Ｄ．）を用い注入量は１０μＬとし、溶離液として０．２Ｍリン酸Ｎａ（ｐＨ６）−アセトニトリル（９８：２）を室温・流速０．４ｍｌ／ｍｉｎで通液し、化学検出（８００ｍＶ）で尿酸を検出した。
1. Ellagic acid Commercially available ellagic acid (manufactured by Wako Pure Chemical Industries, Ltd.) was used.
2. Pomegranate extract The pomegranate fruit hull was extracted with ethanol and distilled to remove impurities, and then an alkaline solution was added and stirred, followed by filtration to obtain a precipitate. The powder obtained by drying the precipitate was used as the pomegranate extract of the present invention. The pomegranate extract contains 90% ellagic acid.
3. Method for measuring serum uric acid level The blood was allowed to stand for 30 to 60 minutes after blood collection, and centrifuged at 10,000 rpm for 10 minutes, and the serum was filtered through filter paper, and the urine was centrifuged at 3,000 rpm for 10 minutes to obtain a supernatant. Serum uric acid levels were analyzed by HPLC under the following conditions.
The HPLC column was Wakosil GP-N6 (15 cm × 4.6 mm ID), the injection volume was 10 μL, and 0.2 M Na phosphate (pH 6) -acetonitrile (98: 2) was used as the eluent at room temperature / flow rate of 0. The solution was passed at a rate of 4 ml / min, and uric acid was detected by chemical detection (800 mV).
４．尿酸クリアランスの算出法
血清中の尿酸濃度、尿中の尿酸濃度、尿量の測定値を基に、以下の算出式を用いて尿酸クリアランス値を算出した。尿酸クリアランスとは、腎臓における血中尿酸の尿への排泄能を示し、尿酸クリアランス値が大きい程、尿酸の排泄作用が強い。
4). Calculation Method of Uric Acid Clearance Based on the measured values of serum uric acid concentration, urine uric acid concentration, and urine volume, uric acid clearance value was calculated using the following calculation formula. Uric acid clearance refers to the ability of blood uric acid to be excreted in the urine in the kidney. The larger the uric acid clearance value, the stronger the excretion of uric acid.
尿酸クリアランス（Ｃｌｕｒ）の算出式：
Ｃｌｕｒ（ｍｌ／ｋｇ／ｍｉｎ）＝Ｕｕｒ・Ｖ／Ｐｕｒ
Ｐｕｒ：血中の尿酸濃度
Ｕｕｒ：尿中の尿酸濃度
Ｖ ：体重あたりの１分間の尿量
Formula for calculating uric acid clearance (Cl ur ):
Cl ur (ml / kg / min) = U ur V / P ur
P ur : blood uric acid concentration
U ur : Uric acid concentration in urine
V: urine volume per minute per body weight
５．血中尿酸値低下活性試験
〔実験例１〕
動物試験法は次の通り行った。つまり、ラット（ＳＤ−ＩＧＳ、オリエンタル酵母社より購入） オス６週令（１群６匹）をＭＦ粉末飼料（オリエンタル酵母社製）にて１週間予備飼育したものを実験に用いた。高尿酸血症を誘発するために２．５％のオキソン酸カリウム（Ａｌｄｒｉｃｈ社製）および２％リボヌクレオ−ス（酵母由来，和光純薬社製）をＭＦ粉末に混餌した（誘発食）。対照群には誘発食を、エラグ酸投与群には、誘発食に純エラグ酸を１％あるいは２％混餌し、試験期間中自由摂取させた。試験開始前および混餌飼育後１，４，８日目に頚静脈より採血を行い、血清中尿酸値を定量した。また、８日目に代謝ゲージにて２４時間尿を採取し、尿量と尿中尿酸値を測定した。
結果：
図１で明らかなように、エラグ酸混餌８日目の血清中尿酸値は、対照群に比べて１％および２％混餌群で有意に低い値を示した。また、図２で明らかなように、１％エラグ酸投与群の尿酸クリアランスが対照群に比べて有意に上昇していた。エラグ酸が、尿酸の体外への排泄を促進することが示された。
5. Blood Urate Decrease Activity Test [Experimental Example 1]
The animal test method was performed as follows. That is, rats (SD-IGS, purchased from Oriental Yeast Co., Ltd.) Male 6-week-old (6 animals per group) preliminarily raised for 1 week in MF powder feed (Oriental Yeast Co., Ltd.) were used for the experiment. To induce hyperuricemia, 2.5% potassium oxonate (manufactured by Aldrich) and 2% ribonuclease (derived from yeast, manufactured by Wako Pure Chemical Industries) were mixed with MF powder (induced diet). In the control group, the induction diet was mixed, and in the ellagic acid administration group, the induction diet was mixed with pure ellagic acid at 1% or 2% and allowed to freely ingest during the test period. Blood was collected from the jugular vein before the start of the test and on
result:
As is clear from FIG. 1, the serum uric acid level on the 8th day of the ellagic acid diet was significantly lower in the 1% and 2% diet groups than in the control group. Further, as is apparent from FIG. 2, the uric acid clearance in the 1% ellagic acid administration group was significantly higher than that in the control group. Ellagic acid has been shown to promote excretion of uric acid outside the body.
〔実験例２〕
ラット（ＳＤ−ＩＧＳ）オス ７週令（１群６匹）をＭＦ粉末飼料にて１週間予備飼育したものを実験に用いた。高尿酸血症を誘発するために２．５％のオキソン酸カリウムおよび２％ リボヌクレオ−スをＭＦ粉末に混餌し、試験期間中自由摂取させた。対照群には３％アラビアゴム水溶液を、ザクロ抽出物投与群には、それぞれ２２５、４５０、９００ｍｇ／ｋｇのザクロ抽出物を３％アラビアゴム水溶液に懸濁させ、１日１回８日間連続強制経口投与した。試験開始前および混餌飼育後１、４、８日目に頚静脈より採血を行い、血清中尿酸値を定量した。また、８日目に代謝ゲージにて２４時間尿を採取し、尿量と尿中尿酸値を測定した。
結果：
図３で明らかなように、ザクロ抽出物投与８日目の血清中尿酸値は、対照群に比べてザクロ抽出物投与群で用量に依存して低い傾向にあり、９００ｍｇ／ｋｇ投与群で有意に低かった。また、図４で明らかなように尿酸クリアランスが、ザクロ抽出物投与群で用量に依存して上昇する傾向を示した。ザクロ抽出物が、尿酸の体外への排泄を促進することが示された。
[Experimental example 2]
Rats (SD-IGS) males 7 weeks old (6 mice per group) preliminarily bred with MF powder feed for 1 week were used in the experiment. To induce hyperuricemia, 2.5% potassium oxonate and 2% ribonucleose were mixed with MF powder and ad libitum during the study period. In the control group, 3% gum arabic aqueous solution was suspended in the pomegranate extract administration group, and 225, 450, 900 mg / kg pomegranate extract was suspended in 3% gum arabic aqueous solution, and forced once a day for 8 days. Orally administered. Blood was collected from the jugular vein before the start of the test and on the 1st, 4th, and 8th days after feeding the mixed food, and the serum uric acid level was quantified. On the 8th day, urine was collected for 24 hours with a metabolic gauge, and urine volume and uric acid level in urine were measured.
result:
As apparent from FIG. 3, the serum uric acid level on the 8th day after pomegranate extract administration tends to be lower depending on the dose in the pomegranate extract administration group than in the control group, and is significant in the 900 mg / kg administration group. It was low. Further, as apparent from FIG. 4, uric acid clearance showed a tendency to increase depending on the dose in the pomegranate extract administration group. Pomegranate extract has been shown to promote excretion of uric acid outside the body.
以下の方法により、エラグ酸又はザクロ抽出物を有効成分とし、尿酸排泄促進のために用いられる医薬品又は飲食品を製造することができる。
＜錠剤タイプ１＞
エラグ酸１００ｍｇ、乳糖８０ｍｇ、トウモロコシデンプン８ｍｇ、ステアリン酸マグネシウム２ｍｇ、以上を１錠分として常法により錠剤化した。この錠剤は、内服用の医薬品又は食品として使用できる。
＜錠剤タイプ２＞
エラグ酸の替わりにザクロ抽出物１２５ｍｇを使用する以外は、錠剤タイプ１と同様の組成として錠剤化した。この錠剤は、内服用の医薬品又は食品として使用できる。
＜飲料タイプ１＞
エラグ酸１ｇ、オレンジジュース（果汁１００％）９８５ｇをミキサーにて混合して均一な飲料とした。これは、内服用の医薬品又は飲料として使用できる。
＜飲料タイプ２＞
ザクロ抽出物１．２５ｇ、オレンジジュース（果汁１００％）９８５ｇをミキサーにて混合して均一な飲料とした。これは、内服用の医薬品又は飲料として使用できる。
By the following method, ellagic acid or a pomegranate extract can be used as an active ingredient to produce a pharmaceutical or a food or drink used for promoting uric acid excretion.
<
100 mg of ellagic acid, 80 mg of lactose, 8 mg of corn starch, 2 mg of magnesium stearate, and the above were tableted by a conventional method. This tablet can be used as a pharmaceutical or food for internal use.
<Tablet type 2>
Tableting was performed with the same composition as
<
1 g of ellagic acid and 985 g of orange juice (fruit juice 100%) were mixed with a mixer to obtain a uniform beverage. This can be used as an internal medicine or beverage.
<Beverage type 2>
A uniform beverage was prepared by mixing 1.25 g of pomegranate extract and 985 g of orange juice (fruit juice 100%) with a mixer. This can be used as an internal medicine or beverage.
Claims (4)
Food / beverage products that contain ellagic acid or pomegranate extract and that are labeled for use in promoting uric acid excretion.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2005096614A JP2006273762A (en) | 2005-03-30 | 2005-03-30 | Uricosuric agent |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2005096614A JP2006273762A (en) | 2005-03-30 | 2005-03-30 | Uricosuric agent |
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| JP2006273762A true JP2006273762A (en) | 2006-10-12 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013035810A (en) * | 2011-08-10 | 2013-02-21 | Bourbon Corp | Agent for inhibiting blood pressure elevation |
| JPWO2013141267A1 (en) * | 2012-03-21 | 2015-08-03 | 株式会社明治 | Polyphenol stabilizer, composition containing the stabilizer and processed product |
| JP2016108253A (en) * | 2014-12-03 | 2016-06-20 | 株式会社バイオリンク販売 | Skin-care cosmetic composition |
| JP2018131419A (en) * | 2017-02-17 | 2018-08-23 | 国立大学法人宇都宮大学 | Pharmaceutical and food compositions for reducing blood uric acid levels |
| WO2020031961A1 (en) | 2018-08-10 | 2020-02-13 | サントリーホールディングス株式会社 | Composition for promoting uric acid excretion, composition for inhibiting urat1 and composition for lowering blood uric acid level |
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2005
- 2005-03-30 JP JP2005096614A patent/JP2006273762A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013035810A (en) * | 2011-08-10 | 2013-02-21 | Bourbon Corp | Agent for inhibiting blood pressure elevation |
| JPWO2013141267A1 (en) * | 2012-03-21 | 2015-08-03 | 株式会社明治 | Polyphenol stabilizer, composition containing the stabilizer and processed product |
| JP2016108253A (en) * | 2014-12-03 | 2016-06-20 | 株式会社バイオリンク販売 | Skin-care cosmetic composition |
| JP2018131419A (en) * | 2017-02-17 | 2018-08-23 | 国立大学法人宇都宮大学 | Pharmaceutical and food compositions for reducing blood uric acid levels |
| WO2020031961A1 (en) | 2018-08-10 | 2020-02-13 | サントリーホールディングス株式会社 | Composition for promoting uric acid excretion, composition for inhibiting urat1 and composition for lowering blood uric acid level |
| KR20210042104A (en) | 2018-08-10 | 2021-04-16 | 산토리 홀딩스 가부시키가이샤 | Composition for promoting uric acid excretion, composition for inhibiting URAT1, and composition for lowering blood uric acid level |
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