JP2022040231A - Xanthine oxydase activity inhibitory composition - Google Patents
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Abstract
Description
本発明は、キサンチンオキシダーゼ活性阻害用組成物に関する。 The present invention relates to a composition for inhibiting xanthine oxidase activity.
高尿酸血症は血中の尿酸値が正常範囲よりも高い状態をいい、今日、我が国では、血清尿酸濃度が７ｍｇ／ｄＬを超える場合を高尿酸血症と定義されている。また、高尿酸血症が原因となる代表的な疾患として痛風、更には腎機能障害や尿路結石等の疾患が知られている。 Hyperuricemia is a condition in which the uric acid level in the blood is higher than the normal range. Today, in Japan, the case where the serum uric acid concentration exceeds 7 mg / dL is defined as hyperuricemia. In addition, gout, renal dysfunction, urinary calculus, and other diseases are known as typical diseases caused by hyperuricemia.
従来、日本では、高尿酸血症やこれに起因する痛風等の患者数はそれほど多くなかったが、近年の生活様式の変化、特に高カロリー、高タンパク、高脂質といった食生活の変化やストレスの増加等に伴い、高尿酸血症や痛風等の尿酸値の上昇が原因となる疾患の患者数は増加傾向にある。このことから、尿酸値の上昇が原因となる疾患を予防、改善することは非常に重要である。 In the past, the number of patients with hyperuricemia and gout caused by it was not so large in Japan, but recent changes in lifestyle, especially changes in diet such as high calories, high protein, and high fat, and stress. With the increase, the number of patients with diseases caused by an increase in uric acid level such as hyperuricemia and gout is increasing. Therefore, it is very important to prevent and improve diseases caused by an increase in uric acid level.
尿酸は、プリン体からヒポキサンチン、キサンチンを経由して生成され、ヒポキサンチンからキサンチンの生成、キサンチンから尿酸の生成にはいずれもキサンチンオキシダーゼが関与する。従って、キサンチンオキシダーゼの活性を阻害することにより、生体内での尿酸の生成を抑制することができる。キサンチンオキシダーゼの活性阻害を利用した高尿酸血症治療薬としてはアロプリノールが知られている（非特許文献１）。 Uric acid is produced from purines via hypoxanthine and xanthine, and xanthine oxidase is involved in the production of xanthine from hypoxanthine and the production of uric acid from xanthine. Therefore, by inhibiting the activity of xanthine oxidase, the production of uric acid in the living body can be suppressed. Allopurinol is known as a therapeutic agent for hyperuricemia utilizing the inhibition of the activity of xanthine oxidase (Non-Patent Document 1).
本発明は、キサンチンオキシダーゼの活性を阻害できる新たな組成物を提供することを目的とする。 An object of the present invention is to provide a novel composition capable of inhibiting the activity of xanthine oxidase.
本発明者らが前記課題に鑑み鋭意研究を重ねたところ、次の植物、すなわちヌルデ、ボタン、アオバノキ、キンマを用いることによって、キサンチンオキシダーゼの活性を阻害できることを見いだした。本発明は該知見に基づき更に検討を重ねた結果完成されたものであり、次に掲げるものである。
項１．ヌルデ、ボタン、アオバノキ及びキンマからなる群より選択される少なくとも１種の植物の加工物を含有する、キサンチンオキシダーゼ活性阻害用組成物。
項２．尿酸生成抑制用である、項１に記載の組成物。
項３．高尿酸血症、痛風、腎機能障害及び尿路結石からなる群より選択される少なくとも１種の予防または改善用である、項１または２に記載の組成物。
項４．食品組成物、医薬組成物または飼料組成物である、項１～３のいずれかに記載の組成物。
As a result of diligent research in view of the above problems, the present inventors have found that the activity of xanthine oxidase can be inhibited by using the following plants, that is, Rhus chinensis, Button, Aoba noki, and Betel. The present invention has been completed as a result of further studies based on the findings, and is as follows.
Item 1. A composition for inhibiting xanthine oxidase activity, which comprises a processed product of at least one plant selected from the group consisting of Rhus chinensis, Button, Aoba noki and Betel.
Item 2. Item 2. The composition according to Item 1, which is used for suppressing uric acid production.
Item 3. Item 2. The composition according to Item 1 or 2, which is for prevention or amelioration of at least one selected from the group consisting of hyperuricemia, gout, renal dysfunction and urinary calculus.
Item 4. Item 6. The composition according to any one of Items 1 to 3, which is a food composition, a pharmaceutical composition or a feed composition.
本発明によれば、キサンチンオキシダーゼの活性を阻害できる。このため、本発明によれば、尿酸の生成を抑制することができる。このことから、本発明の組成物は、尿酸の生
成に起因する疾患、特に尿酸値の上昇に基づく各種症状の予防または改善を目的として使用することができる。
According to the present invention, the activity of xanthine oxidase can be inhibited. Therefore, according to the present invention, the production of uric acid can be suppressed. From this, the composition of the present invention can be used for the purpose of preventing or ameliorating diseases caused by the production of uric acid, particularly various symptoms based on an increase in uric acid level.
本発明は、ヌルデ、ボタン、アオバノキ及びキンマからなる群より選択される少なくとも１種の植物の加工物を含有する、キサンチンオキシダーゼ活性阻害用組成物を提供する。 The present invention provides a composition for inhibiting xanthine oxidase activity, which comprises a processed product of at least one plant selected from the group consisting of Rhus chinensis, Button, Aoba noki and Betel.
本発明の組成物に有効成分として含まれる前記植物の加工物の原料として、ヌルデ、ボタン、アオバノキ、キンマが挙げられる。 Examples of the raw material of the processed plant product contained as an active ingredient in the composition of the present invention include rhus chinensis, button, aoba noki, and betel.
ヌルデ（Rhus javanica L.）は、ウルシ科のヌルデ属に属する植物である。ボタン（Paeonia suffruticosa Andrews）は、ボタン科のボタン属に属する植物である。アオバノキ（Symplocos cochinchinensis (Lour.) S.Moore）は、ハイノキ科のハイノキ属に属する
植物である。キンマ（Piper betle L.）は、コショウ科のコショウ属に属する植物である。これらは１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。
Rhus javanica L. is a plant belonging to the genus Sumac of the family Rhus chinensis. Buttons (Paeonia suffruticosa Andrews) are plants belonging to the genus Peony of the Peony family. Aoba no Ki (Symplocos cochinchinensis (Lour.) S. Moore) is a plant belonging to the genus Symplocos of the Symplocaceae family. Betel (Piper betle L.) is a plant belonging to the genus Pepper in the Piperaceae family. These may be used alone or in combination of two or more.
該植物であれば使用部位は特に限定されないが、葉、茎、果実、嚢状虫瘻、花、芽、枝、樹皮、根茎、種子、種皮等が例示され、各植物に応じて適宜選択すればよい。より好ましくは葉、茎、果実、嚢状虫瘻等が例示され、更に好ましくはヌルデの嚢状虫瘻（五倍子ともよばれる）、ボタンの葉、アオバノキの葉、キンマの葉が例示される。使用部位として、１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 If it is the plant, the site of use is not particularly limited, but leaves, stems, fruits, cyst fistulas, flowers, buds, branches, bark, rhizomes, seeds, seed coats, etc. are exemplified, and it is appropriately selected according to each plant. Just do it. More preferably, leaves, stems, fruits, saccular fistulas and the like are exemplified, and more preferably, Rhus chinensis saccular fistula (also called quintuplet), button leaves, aoba tree leaves, betel leaves and the like are exemplified. As the site of use, one type may be used alone, or two or more types may be used in combination.
本発明において植物の加工物とは、前記原料となる植物の粉砕物、乾燥物、抽出物等が挙げられる。 In the present invention, the processed plant product includes a crushed product, a dried product, an extract, etc. of the plant as a raw material.
粉砕物は、ジェットミル等の本分野で公知の粉砕器により前記植物を粉砕したものであれば特に限定されない。 The crushed product is not particularly limited as long as the plant is crushed by a crusher known in the art such as a jet mill.
乾燥物は、前記植物を乾燥させたものであれば特に限定されず、天日乾燥、遠赤外線照射、乾燥機（熱風乾燥、冷風乾燥、真空凍結乾燥等）等の従来公知の乾燥方法に従って得ることができる。本発明において乾燥物の形態は問わず、植物体そのものの乾燥物、乾燥物の粉砕物等のいずれでもよい。乾燥粉砕物は、前記粉砕物と同様の方法に従って乾燥物を粉砕することにより得ることができる。また、本発明においては乾燥物として、原料となる植物を発酵処理や酵素処理した後乾燥して得られたものを使用することもできる。 The dried product is not particularly limited as long as it is a dried plant, and can be obtained according to a conventionally known drying method such as sun drying, far infrared irradiation, and a dryer (hot air drying, cold air drying, vacuum freezing drying, etc.). be able to. In the present invention, the form of the dried product is not limited, and any of the dried product of the plant itself, the crushed product of the dried product, and the like may be used. The dried pulverized product can be obtained by pulverizing the dried product according to the same method as the pulverized product. Further, in the present invention, as a dried product, a product obtained by fermenting or enzymatically treating a plant as a raw material and then drying it can also be used.
抽出物の製造方法（抽出方法）及び抽出条件等は特に限定されず、従来公知の方法に従えばよい。例えば、前記植物をそのまま、必要に応じて裁断、粉砕または乾燥等したのち、搾取または溶媒抽出によって抽出物を得ることができる。溶媒抽出の方法としては、本分野において公知の方法を採用すればよく、例えば水（温水、熱水を含む）抽出、アルコール抽出、超臨界抽出等の従来公知の抽出方法を利用することができる。 The method for producing the extract (extraction method), the extraction conditions, and the like are not particularly limited, and conventionally known methods may be followed. For example, the plant can be cut, crushed, dried or the like as it is, if necessary, and then exploited or solvent-extracted to obtain an extract. As the solvent extraction method, a method known in the art may be adopted, and conventionally known extraction methods such as water (including hot water and hot water) extraction, alcohol extraction, supercritical extraction and the like can be used. ..
溶媒抽出を行う場合、溶媒としては例えば水；メタノール、エタノール、イソプロパノール等の低級アルコールや、プロピレングリコール、１，３－ブチレングリコール等の多価アルコール等のアルコール類（無水、含水の別を問わない）；アセトン等のケトン類、ジエチルエーテル、ジオキサン、アセトニトリル、酢酸エチルエステル等のエステル類、キシレン、ベンゼン、クロロホルム等が挙げられる。溶媒として好ましくは水、低級アルコール、１，３－ブチレングリコール等であり、より好ましくは水、メタノール、エタノール、１，３－ブチレングリコールであり、更に好ましくはメタノール、含水エタノールである。これらの溶媒は１種単独で使用してもよく、２種以上を組み合わせて使用しても
よい。
When solvent extraction is performed, the solvent may be, for example, water; lower alcohols such as methanol, ethanol and isopropanol, and alcohols such as polyhydric alcohols such as propylene glycol and 1,3-butylene glycol (whether anhydrous or water-containing). ); Ketones such as acetone, esters such as diethyl ether, dioxane, acetonitrile and ethyl acetate, xylene, benzene, chloroform and the like. The solvent is preferably water, a lower alcohol, 1,3-butylene glycol or the like, more preferably water, methanol, ethanol or 1,3-butylene glycol, and further preferably methanol or hydrous ethanol. These solvents may be used alone or in combination of two or more.
本発明において、このように溶媒抽出を経て得た抽出物を特に溶媒抽出物と称することができる。更に、本発明を制限するものではないが、前述のように例えば溶媒として水を用いた場合は水抽出物、低級アルコール類を用いた場合は低級アルコール抽出物、エタノールを用いた場合はエタノール抽出物等と称することができる。 In the present invention, the extract thus obtained through solvent extraction can be particularly referred to as a solvent extract. Further, although not limiting the present invention, as described above, for example, a water extract when water is used as a solvent, a lower alcohol extract when lower alcohols are used, and an ethanol extract when ethanol is used. It can be called a thing or the like.
得られた抽出物は、そのままの状態で使用してもよく、乾燥させて粉末状や顆粒状等の固形の状態で使用してもよい。また、必要に応じて、得られた抽出物に精製、濃縮処理、高活性画分の分離処理等を施してもよい。本発明を制限するものではないが、精製処理としては、濾過、イオン交換樹脂や活性炭カラム等を用いた吸着、脱色といった処理が挙げられる。また、濃縮処理としては、エバポレーター等の常法を利用できる。また、高活性画分の分離処理としては、ゲル濾過、吸着処理、シリカゲルカラムクロマトグラフィー、ＨＰＬＣ（High performance liquid chromatography）等の公知の分離処理を利用できる。 The obtained extract may be used as it is, or may be dried and used in a solid state such as powder or granules. Further, if necessary, the obtained extract may be subjected to purification, concentration treatment, separation treatment of highly active fractions and the like. Although not limiting the present invention, examples of the purification treatment include treatments such as filtration, adsorption using an ion exchange resin, an activated carbon column, and decolorization. Further, as the concentration treatment, a conventional method such as an evaporator can be used. Further, as the separation treatment of the highly active fraction, known separation treatments such as gel filtration, adsorption treatment, silica gel column chromatography, and HPLC (High performance liquid chromatography) can be used.
また、例えば、前述のようにして得られた抽出物（更にはその乾燥物、精製処理物、濃縮処理物、高活性画分）を、凍結乾燥処理に供して粉末化する方法、必要に応じてデキストリン、コーンスターチ、アラビアゴム等の賦形剤を添加して、スプレードライ処理により粉末化する方法等の従来公知の方法に従って粉末化し、本発明で用いる抽出物としてもよい。また、該抽出物を、必要に応じて水、エタノール等に溶解して用いてもよい。 Further, for example, a method for pulverizing the extract obtained as described above (further, its dried product, purified product, concentrated product, highly active fraction) by freeze-drying treatment, if necessary. The extract may be used in the present invention by adding excipients such as dextrin, cornstarch, and gum arabic and pulverizing according to a conventionally known method such as a method of pulverizing by spray-drying. Further, the extract may be used by dissolving it in water, ethanol or the like, if necessary.
前記植物の抽出物として好ましくは、原料となる植物（使用部位）を乾燥、破砕及び／または裁断し、好適な溶媒を使用して抽出、濾過して得られる抽出物、また、このようにして得られる抽出物を更に乾燥させることにより得られる抽出物が例示される。本発明を制限するものではなく、各植物または使用部位に応じて当業者が適宜抽出すればよいが、抽出物は、原料となる植物を１００ｇあたり、より好ましくは該植物の乾燥物、破砕物及び／または裁断物を１００ｇあたり、抽出溶媒１～５０リットルに浸漬させて、任意の温度（例えば１５～９０℃）で、必要に応じて攪拌しながら、任意の時間（例えば１０分～２４時間）抽出を行い、次いで濾過することにより得ることができる。本発明において植物の加工物として好ましくは植物抽出物（その乾燥物等を含む）である。 The extract of the plant is preferably an extract obtained by drying, crushing and / or cutting a plant (site of use) as a raw material, extracting and filtering using a suitable solvent, and in this way. An example is an extract obtained by further drying the obtained extract. The present invention is not limited, and a person skilled in the art may appropriately extract the extract according to each plant or site of use, but the extract is 100 g of a plant as a raw material, more preferably a dried product or a crushed product of the plant. And / or the cut product is immersed in 1 to 50 liters of the extraction solvent per 100 g, and is stirred at an arbitrary temperature (for example, 15 to 90 ° C.) as necessary for an arbitrary time (for example, 10 minutes to 24 hours). ) It can be obtained by performing extraction and then filtering. In the present invention, the processed plant is preferably a plant extract (including a dried product thereof).
本発明において使用する植物の加工物は市販品でもよく、市販品に対して更に乾燥等の処理を適宜施したものでもよい。 The processed plant product used in the present invention may be a commercially available product, or may be a commercially available product that has been further subjected to a treatment such as drying.
このようにして得た植物の加工物は、１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。 The processed plant product thus obtained may be used alone or in combination of two or more.
本発明の組成物中の前記植物の加工物の含有量は、本発明の効果が得られる限り制限されない。組成物中、前記植物の加工物が、乾燥物換算で、０質量％より多く含まれていることが例示され、好ましくは前記植物の加工物が、乾燥物換算で、５～９９．９質量％が例示され、より好ましくは１０～７５質量％、更に好ましくは２５～５０質量％が例示される。２種以上の加工物を用いる場合、その総量が該値を充足する。加工物の乾燥物は、加工物を凍結乾燥処理することにより得られる。凍結乾燥処理は、一般的なエバポレーターを用いた減圧濃縮及び真空状態での凍結乾燥により行う。より詳細な処理手順は後述する実施例に従う。 The content of the processed plant product in the composition of the present invention is not limited as long as the effect of the present invention is obtained. It is exemplified that the processed product of the plant is contained in the composition in an amount of more than 0% by mass in terms of dry matter, and preferably the processed product of the plant is 5 to 99.9 mass in terms of dry matter. %, More preferably 10 to 75% by mass, still more preferably 25 to 50% by mass. When two or more kinds of processed products are used, the total amount satisfies the value. The dried product of the processed product is obtained by freeze-drying the processed product. The freeze-drying treatment is carried out by concentration under reduced pressure using a general evaporator and freeze-drying in a vacuum state. A more detailed processing procedure follows the examples described later.
また、本発明の組成物において、前記植物の加工物の投与（摂取）量は、本発明の効果が奏される限り特に限定されず、対象者（対象動物）の体格、年齢、症状、適用形態、使用目的、尿酸値の程度、期待される効果の程度等に応じて適宜設定すればよい。本発明を
制限するものではないが、１日投与（摂取）量として、体重６０ｋｇの成人を基準として、前記植物の加工物は総量で（乾燥質量換算として）、好ましくは１０～２０００ｍｇ、より好ましくは１００～１０００ｍｇ、更に好ましくは４００～６００ｍｇが例示される。本発明の組成物は、１日あたり単回投与（摂取）であってもよく複数回投与（摂取）であってもよい。
Further, in the composition of the present invention, the administration (ingestion) amount of the processed plant product is not particularly limited as long as the effect of the present invention is exhibited, and the physique, age, symptoms and application of the subject (target animal). It may be appropriately set according to the form, purpose of use, degree of uric acid level, degree of expected effect, and the like. Although not limiting the present invention, the daily dose (intake) of the processed plant is preferably 10 to 2000 mg, more preferably 10 to 2000 mg, based on an adult having a body weight of 60 kg (in terms of dry mass). Is 100 to 1000 mg, more preferably 400 to 600 mg. The composition of the present invention may be a single dose (ingestion) or a plurality of doses (ingestion) per day.
本発明の組成物は、経口、非経口の別を問わない。本発明の組成物の形態も制限されず、目的に応じて適宜設定すればよい。本発明の組成物の形態として、液剤、乳剤、懸濁剤、シロップ剤、エキス剤、酒精剤、エリキシル剤等の液状形態、散剤、顆粒剤、細粒剤、錠剤、丸剤、カプセル剤（ハードカプセル、ソフトカプセルを含む）、トローチ、チュアブル、ゲル状、クリーム状、ペースト状、ムース状、シート状、液状形態の凍結乾燥物等の半固形または固形形態、この他、エアゾール剤、貼付剤、ハップ剤、経皮吸収型製剤等の各種形態が例示される。 The composition of the present invention may be oral or parenteral. The form of the composition of the present invention is not limited, and may be appropriately set according to the intended purpose. The forms of the composition of the present invention include liquid forms such as liquids, emulsions, suspensions, syrups, extracts, liquor, erixyls, powders, granules, fine granules, tablets, rounds, capsules ( Semi-solid or solid forms such as hard capsules (including hard capsules and soft capsules), troches, chewables, gels, creams, pastes, mousses, sheets, and liquid freeze-dried products, as well as aerosols, patches, and haps. Various forms such as an agent and a transdermal absorption type preparation are exemplified.
また、例えば本発明の組成物が固形形態である場合、これは水等と混合して使用してもよく、また、本発明の組成物は徐放性の剤形であってもよい。また、例えば錠剤は、必要に応じて、従来公知の剤皮を施した錠剤、例えば糖衣錠、ゼラチン被包錠、腸溶被錠、フィルムコーティング錠、あるいは二重錠、多層錠とすることができる。 Further, for example, when the composition of the present invention is in a solid form, it may be mixed with water or the like and used, and the composition of the present invention may be in a sustained release dosage form. Further, for example, the tablet may be a conventionally known coated tablet, for example, a sugar-coated tablet, a gelatin-encapsulated tablet, an enteric-coated tablet, a film-coated tablet, a double tablet, or a multi-layer tablet, if necessary. ..
また、本発明の組成物の使用態様も制限されず、目的に応じて適宜設定すればよい。本発明の組成物の使用態様として、食品組成物（飲料を含む、保健機能食品（特定保健用食品、栄養機能食品、機能性表示食品、サプリメント等を含む）、病者用食品を含む）、医薬組成物、飼料組成物、また、食品組成物、医薬組成物、飼料等への添加剤等として使用することができる。 Further, the mode of use of the composition of the present invention is not limited, and may be appropriately set according to the intended purpose. As a mode of use of the composition of the present invention, food compositions (including beverages, health functional foods (including specified health foods, nutritional functional foods, foods with functional claims, supplements, etc.), foods for the sick, etc.), It can be used as a pharmaceutical composition, a feed composition, an additive to a food composition, a pharmaceutical composition, a feed, or the like.
本発明の組成物は、前述の各種形態、使用態様等における従来公知の通常の手順に従い製造すればよく、必要に応じて、薬学的に許容される成分、香粧品科学的に許容される成分、可食性の成分といった任意の成分と混合等して製造すればよい。該任意の成分として、溶剤（水、メタノール、エタノール、イソプロパノール等の低級アルコール、プロピレングリコール、１，３－ブチレングリコール等の多価アルコール等のアルコール類（無水、含水の別を問わない）等）、賦形剤、崩壊剤、希釈剤、滑沢剤、香料、着色料、甘味料、矯味剤、懸濁剤、湿潤剤、乳化剤、可溶化剤、分散剤、緩衝剤、結合剤、浸透促進剤、安定剤、増量剤、防腐剤、増粘剤、ｐＨ調整剤、界面活性剤、コーティング剤、吸収促進剤、吸着剤、充填剤、酸化防止剤、抗炎症剤、清涼剤、皮膜形成剤、ゲル化剤、アミノ酸、ビタミン、酵素、各種栄養成分等が例示される。これらは１種単独で使用してもよく、２種以上を組み合わせて使用してもよく、その含有量も適宜決定すればよい。 The composition of the present invention may be produced according to conventionally known conventional procedures in the above-mentioned various forms, usage modes, etc., and if necessary, pharmaceutically acceptable ingredients and cosmetic scientifically acceptable ingredients. , It may be manufactured by mixing with an arbitrary component such as an edible component. As the optional component, a solvent (water, lower alcohol such as methanol, ethanol, isopropanol, alcohols such as propylene glycol, polyhydric alcohol such as 1,3-butylene glycol (whether anhydrous or water-containing), etc.) and the like). , Excipients, disintegrants, diluents, lubricants, fragrances, colorants, sweeteners, flavoring agents, suspending agents, wetting agents, emulsifiers, solubilizers, dispersants, buffers, binders, penetration promoting Agents, stabilizers, bulking agents, preservatives, thickeners, pH regulators, surfactants, coatings, absorption promoters, adsorbents, fillers, antioxidants, anti-inflammatory agents, refreshing agents, film-forming agents , Gelling agents, amino acids, vitamins, enzymes, various nutritional components and the like are exemplified. These may be used alone or in combination of two or more, and the content thereof may be appropriately determined.
本発明において、組成物の対象者（対象動物）も制限されないが、ヒト、ヒト以外の哺乳動物、鳥類、爬虫類等が例示される。ヒト以外の哺乳動物としては、キサンチンオキシダーゼが尿酸の生成促進を図っている動物が挙げられ、マウス、ラット、モルモット、ウサギ、イヌ、ネコ、サル、ブタ、牛、馬等の動物、好ましくはマウス、ラット、モルモット、ウサギ、イヌ、サル等の動物が例示される。 In the present invention, the subject (target animal) of the composition is not limited, but humans, non-human mammals, birds, reptiles and the like are exemplified. Examples of mammals other than humans include animals in which xanthin oxidase promotes the production of uric acid, and animals such as mice, rats, guinea pigs, rabbits, dogs, cats, monkeys, pigs, cows, and horses, preferably mice. , Rats, guinea pigs, rabbits, dogs, monkeys and the like.
本発明の組成物によれば、前記植物の加工物を有効成分としてキサンチンオキシダーゼの活性を阻害することができる。このことから、本発明は、前記植物の加工物を用いることを特徴とするキサンチンオキシダーゼ活性阻害用組成物の製造方法を提供するといえる。また、本発明は、前記植物の加工物を調製する工程を含有する、キサンチンオキシダーゼ活性阻害用組成物の製造方法を提供するといえる。また、本発明は、前記植物の加工物を用いることを特徴とする、キサンチンオキシダーゼ活性阻害方法を提供するといえる。 According to the composition of the present invention, the activity of xanthine oxidase can be inhibited by using the processed product of the plant as an active ingredient. From this, it can be said that the present invention provides a method for producing a composition for inhibiting xanthine oxidase activity, which is characterized by using the processed product of the plant. Further, it can be said that the present invention provides a method for producing a composition for inhibiting xanthine oxidase activity, which comprises a step of preparing a processed product of the plant. Further, it can be said that the present invention provides a method for inhibiting xanthine oxidase activity, which is characterized by using the processed product of the plant.
このように本発明の組成物によれば、キサンチンオキシダーゼの活性を阻害できる。このことから、本発明によれば生体内での尿酸の生成を抑制することができ、キサンチンオキシダーゼの活性や尿酸生成に起因する疾患、特に尿酸値の上昇に基づく各種症状の予防または改善を目的として本発明の組成物を使用することができる。 Thus, according to the composition of the present invention, the activity of xanthine oxidase can be inhibited. Therefore, according to the present invention, it is possible to suppress the production of uric acid in the living body, and it is an object to prevent or improve the activity of xanthine oxidase and diseases caused by the production of uric acid, particularly various symptoms based on an increase in uric acid level. The composition of the present invention can be used as.
このため、本発明の組成物は、本発明を制限するものではないが、高尿酸血症、痛風、腎機能障害、尿路結石等の予防または改善に有用である。また、本発明の組成物は、生体内での尿酸の上昇が気になる対象者、尿酸値が気になる対象者、尿酸値の上昇を穏やかにしたい対象者、プリン体が気になる対象者、尿酸値が高めの対象者、高尿酸血症、痛風、腎機能障害、尿路結石等の尿酸値の上昇に起因する疾患が気になる対象者等に好ましく適用することができる。 Therefore, the composition of the present invention does not limit the present invention, but is useful for preventing or ameliorating hyperuricemia, gout, renal dysfunction, urinary calculus and the like. In addition, the composition of the present invention is a subject who is concerned about an increase in uric acid in a living body, a subject who is concerned about an increase in uric acid level, a subject who wants to moderate the increase in uric acid level, and a subject who is concerned about purines. It can be preferably applied to subjects with high uric acid levels, subjects who are concerned about diseases caused by elevated uric acid levels such as hyperuricemia, gout, renal dysfunction, and urinary stones.
また、本発明の組成物は、尿酸生成抑制薬、高尿酸血症治療薬、痛風治療薬、腎機能障害治療薬、尿路結石治療薬等としても使用できる The composition of the present invention can also be used as a uric acid production inhibitor, a hyperuricemia therapeutic agent, a gout therapeutic agent, a renal dysfunction therapeutic agent, a urinary calculus therapeutic agent and the like.
以下、実施例を示して本発明をより詳細に説明するが、本発明はこれらに限定されない。 Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
１．植物の加工物の調製
植物の加工物の原料として、ヌルデ（Rhus javanica L.）、ボタン（Paeonia suffruticosa Andrews）、アオバノキ（Symplocos cochinchinensis (Lour.) S.Moore）、キンマ
（Piper betle L.）を使用し、次の抽出物を準備した。
1. 1. Preparation of processed plant products Rhus javanica L., peony (Paeonia suffruticosa Andrews), Aoba noki (Symplocos cochinchinensis (Lour.) S. Moore), and betel (Piper betle L.) are used as raw materials for processed plant products. Used and prepared the following extracts.
ヌルデ
ヌルデの嚢状虫瘻の抽出物（日本新薬社製特注ヌルデエキス末、粉末乾燥物）を用いた。本抽出物は、ヌルデの嚢状虫瘻の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。
An extract of Nurudenurude 's saccular gall fistula (custom-made Nurude extract powder manufactured by Nippon Shinyaku Co., Ltd., dried powder) was used. This extract was obtained by crushing a dried product of Rhus chinensis fistula, adding methanol for extraction, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components had been removed. Is.
ボタン
ボタンの葉の抽出物（日本新薬社製特注ボタンエキス末、粉末乾燥物）を用いた。本抽出物は、ボタンの葉の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。
Button button leaf extract (custom button extract powder manufactured by Nippon Shinyaku Co., Ltd., powder dried product) was used. The present extract was obtained by crushing a dried product of button leaves, adding methanol for extraction, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components had been removed.
アオバノキ
アオバノキの葉の抽出物（日本新薬社製特注アオバノキエキス末、粉末乾燥物）を用いた。本抽出物は、アオバノキの葉の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。
Aoba noki Aoba noki leaf extract (custom-made Aoba noki extract powder manufactured by Nippon Shinyaku Co., Ltd., powder dried product) was used. This extract was obtained by crushing a dried product of Aoba noki leaves, adding methanol to extract the extract, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components had been removed.
キンマ
キンマの葉の抽出物（日本新薬社製特注キンマエキス末、粉末乾燥物）を用いた。本抽出物は、キンマの葉の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。
Kinma Kinma leaf extract (custom Kinma extract powder manufactured by Nippon Shinyaku Co., Ltd., powder dried product) was used. This extract was obtained by crushing a dried betel leaf, adding methanol to extract the extract, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components had been removed.
２．キサンチンオキシダーゼ阻害活性の測定
前記１．の各抽出物を水と混合し、得られた混合液（抽出物40μg/mL）とキサンチンオキシダーゼ（0.04U/mL）（商品名キサンチンオキシダーゼ、オリエンタル酵母社製）とを50μLずつ混合し、25℃で15分間インキュベートした。その後、キサンチン（0.4mM）（商
品名キサンチン、和光純薬工業社製）を100μL添加し、25℃で15分間インキュベートし、マイクロプレートリーダー（Infinite M200 Pro、テカン社製）を用いて紫外吸収測定（295nm）を行った。なお、前記抽出物に代えて同量の水を用いた以外は同様にしてインキュベートしたものを対照とした。（n=3）
2. 2. Measurement of xanthine oxidase inhibitory activity 1. Each extract of the above is mixed with water, and 50 μL of the obtained mixture (extract 40 μg / mL) and xanthine oxidase (0.04 U / mL) (trade name: xanthine oxidase, manufactured by Oriental Yeast Co., Ltd.) are mixed, and 25 Incubated at ° C for 15 minutes. Then, add 100 μL of xanthine (0.4 mM) (trade name: Xanthine, manufactured by Wako Pure Chemical Industries, Ltd.), incubate at 25 ° C for 15 minutes, and measure ultraviolet absorption using a microplate reader (Infinite M200 Pro, manufactured by Tecan). (295 nm) was performed. In addition, those incubated in the same manner except that the same amount of water was used instead of the extract was used as a control. (N = 3)
キサンチンオキシダーゼ阻害率は次のようにして算出した。
キサンチンオキシダーゼ阻害率（％）＝（１-A/B）×100
A＝抽出物の添加試験区の吸光度
B＝水（対照、抽出物の非添加）の添加試験区の吸光度
The xanthine oxidase inhibition rate was calculated as follows.
Xanthine oxidase inhibition rate (%) = (1-A / B) x 100
A = Absorbance of the test group to which the extract is added
B = Absorbance of water (control, no extract added) addition test group
３．結果
結果を表１に示す。
3. 3. Results The results are shown in Table 1.
表１から明らかなように、いずれの植物の抽出物においてもキサンチンオキシダーゼ活性を阻害できた。 As is clear from Table 1, the xanthine oxidase activity could be inhibited in any of the plant extracts.
これにより、ヌルデ、ボタン、アオバノキ、キンマの各加工物によれば、キサンチンオキシダーゼの活性を阻害できることが分かった。このことから、該加工物は、キサンチンオキシダーゼ活性により促進される尿酸生成の抑制、キサンチンオキシダーゼの活性や尿酸生成に起因する疾患の予防または改善に利用できることが確認された。 From this, it was found that the activity of xanthine oxidase can be inhibited according to the processed products of Rhus chinensis, Button, Aoba noki, and Betel. From this, it was confirmed that the processed product can be used for suppression of uric acid production promoted by xanthine oxidase activity, prevention or improvement of xanthine oxidase activity and diseases caused by uric acid production.
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