JP7058939B2 - Composition for inhibiting phosphodiesterase 5 activity - Google Patents
Composition for inhibiting phosphodiesterase 5 activity Download PDFInfo
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- JP7058939B2 JP7058939B2 JP2016256466A JP2016256466A JP7058939B2 JP 7058939 B2 JP7058939 B2 JP 7058939B2 JP 2016256466 A JP2016256466 A JP 2016256466A JP 2016256466 A JP2016256466 A JP 2016256466A JP 7058939 B2 JP7058939 B2 JP 7058939B2
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Description
本発明は、ホスホジエステラーゼ５活性阻害用組成物に関する。 The present invention relates to a composition for inhibiting phosphodiesterase 5 activity.
ホスホジエステラーゼ（phosphodiesterase、ＰＤＥ）は、サイクリックＧＭＰ（ｃＧＭＰ）やサイクリックＡＭＰ（ｃＡＭＰ）を加水分解する酵素であり、哺乳動物では複数のファミリーが存在する。 Phosphodiesterase (PDE) is an enzyme that hydrolyzes cyclic GMP (cGMP) and cyclic AMP (cAMP), and there are multiple families in mammals.
このうち、ホスホジエステラーゼ５（ＰＤＥ５）は、主にｃＧＭＰの分解に関与する。ｃＧＭＰは、細胞内セカンドメッセンジャーとして作用し、平滑筋を弛緩させ、血流を増加させる。このため、ＰＤＥ５の活性を抑制することにより、平滑筋が弛緩し、血流が増加する。 Of these, phosphodiesterase 5 (PDE5) is mainly involved in the degradation of cGMP. cGMP acts as an intracellular second messenger, relaxing smooth muscle and increasing blood flow. Therefore, by suppressing the activity of PDE5, smooth muscle is relaxed and blood flow is increased.
この作用を利用した薬剤として、今日、ＰＤＥ５阻害薬が知られており、代表的なものとしてシルデナフィルクエン酸塩を有効成分とする医薬品等が知られている。ＰＤＥ５阻害薬は、ＰＤＥ５の活性を阻害してｃＧＭＰの分解を抑制し、局所血流を増加させることにより、陰茎***能力の低下、膀胱や前立腺の機能低下、肺高血圧症といった症状の改善を目的として活用されている。 As a drug utilizing this action, a PDE5 inhibitor is known today, and a typical drug such as a drug containing sildenafil citrate as an active ingredient is known. PDE5 inhibitors aim to improve symptoms such as decreased penile erectile capacity, decreased bladder and prostate function, and pulmonary hypertension by inhibiting the activity of PDE5, suppressing the degradation of cGMP, and increasing local blood flow. It is used as.
また、例えばクロショウガが、ＰＤＥの活性を阻害できることが知られている（特許文献１）。 Further, it is known that, for example, black ginger can inhibit the activity of PDE (Patent Document 1).
本発明は、ＰＤＥ５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 PDE5.
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、キイチゴ属（Rubus）、ザクロ属（Punica）、シモツケソウ属（Filipendula）、ヤマモモ属（Myrica）、エウゲニア属（Eugenia）、サルスベリ属（Lagerstroemia）、モモタマナ属（Terminalia）、アカミノキ属（Haematoxylon）、ソバカズラ属（Fallopia）またはカギカズラ属（Uncaria）に属する植物によれば、ＰＤＥ５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．キイチゴ属（Rubus）、ザクロ属（Punica）、シモツケソウ属（Filipendula）、ヤマモモ属（Myrica）、エウゲニア属（Eugenia）、サルスベリ属（Lagerstroemia）、モモタマナ属（Terminalia）、アカミノキ属（Haematoxylon）、ソバカズラ属（Fallopia）及びカギカズラ属（Uncaria）からなる群より選択される少なくとも１つの植物の加工物を含有する、ホスホジエステラーゼ５活性阻害用組成物。
項２．キイチゴ属に属する植物が、ヒマラヤブラックベリー（Rubus armeniacus Focke）、セイヨウヤブイチゴ（Rubus fruticosus）及びアメリカイチゴ（Rubus strigosus）からなる群より選択される少なくとも１つである、項１に記載の組成物。
項３．ザクロ属に属する植物が、ザクロ（Punica granatum）である、項１に記載の組成物。
項４．シモツケソウ属に属する植物が、セイヨウナツユキソウ（Filipendula ulmaria）である、項１に記載の組成物。
項５．ヤマモモ属に属する植物が、シロコヤマモモ（Myrica cerifera）及びヤマモモ（Myrica rubura）からなる群より選択される少なくとも１つである、項１に記載の組成物。
項６．エウゲニア属に属する植物が、タチバナアデク（Eugenia uniflora）及びクローブ（Eugenia aromaticum）からなる群より選択される少なくとも１つである、項１に記載の組成物。
項７．サルスベリ属に属する植物が、バナバ（Lagerstroemia speciosa）である、項１に記載の組成物。
項８．モモタマナ属に属する植物が、モモタマナ（Terminalia catappa）及びセイタカミロバラン（Terminalia bellirica）からなる群より選択される少なくとも１つである、項１に記載の組成物。
項９．アカミノキ属に属する植物が、アカミノキ（Haematoxylon campechianum）である、項１に記載の組成物。
項１０．ソバカズラ属に属する植物が、イタドリ（Fallopia japonica）である、項１に記載の組成物。
項１１．カギカズラ属に属する植物が、キャッツクロー（Uncaria guianensis）である、項１に記載の組成物。
項１２．陰茎***機能、下部尿路機能障害、前立腺肥大及び肺高血圧症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１～１１のいずれかに記載の組成物。
項１３．食品組成物、医薬組成物または飼料組成物である、項１～１２のいずれかに記載の組成物。
In view of the above problems, the present inventors have conducted extensive research on the following plants, namely, the following plants: Haematoxylum (Rubus), Pomegranate (Punica), Fallopia (Filipendula), Bayberry (Myrica), and Eugenia (Eugenia). ), Lagerstroemia, Terminalia, Haematoxylon, Fallopia or Uncaria, found to be able to inhibit the activity of PDE5. The present invention has been completed as a result of further studies based on the findings, and is as follows.
Item 1. The genus Rubus, Punica, Filipendula, Bayberry, Eugenia, Lagerstroemia, Terminalia, Haematoxylon, Fallopia (Fallopia) and Uncaria (Uncaria), a composition for inhibiting the activity of phosphodiesterase 5, which comprises a processed product of at least one plant selected from the group.
Item 2. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Rubus is at least one selected from the group consisting of Himalayan blackberry (Rubus armeniacus Focke), Rubus fruticosus and Rubus strigosus. ..
Item 3. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Pomegranate is pomegranate (Punica granatum).
Item 4. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Filipendula is Filipendula ulmaria.
Item 5. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Bayberry is at least one selected from the group consisting of Southern wax myrtle (Myrica cerifera) and Bayberry (Myrica rubura).
Item 6. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Eugenia is at least one selected from the group consisting of Tachibana adec (Eugenia uniflora) and Clove (Eugenia aromaticum).
Item 7. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Crape myrtle is Banaba (Lagerstroemia speciosa).
Item 8. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Indian-almond is at least one selected from the group consisting of Momotamana (Terminalia catappa) and Seitakamirobaran (Terminalia bellirica).
Item 9. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Haematoxylum is Haematoxylon campechianum.
Item 10. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Fallopia is Japanese knotweed (Fallopia japonica).
Item 11. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Uncaria is Cat's claw (Uncaria guianensis).
Item 12. Item 6. The composition according to any one of Items 1 to 11, which is for prevention or amelioration of at least one selected from the group consisting of penile erectile function, lower urinary tract dysfunction, benign prostatic hyperplasia and pulmonary hypertension.
Item 13. Item 6. The composition according to any one of Items 1 to 12, which is a food composition, a pharmaceutical composition or a feed composition.
本発明によれば、ＰＤＥ５の活性を阻害できる。このため、本発明の組成物は、ｃＧＭＰの分解に伴う血流低下に起因する疾患、例えば陰茎***機能、下部尿路機能障害、前立腺肥大、肺高血圧症といった疾患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 PDE5 can be inhibited. Therefore, the composition of the present invention is used for the purpose of preventing or ameliorating diseases caused by a decrease in blood flow associated with the decomposition of cGMP, such as penile erectile function, lower urinary tract dysfunction, benign prostatic hyperplasia, and pulmonary hypertension. can do.
本発明は、キイチゴ属（Rubus）、ザクロ属（Punica）、シモツケソウ属（Filipendula）、ヤマモモ属（Myrica）、エウゲニア属（Eugenia）、サルスベリ属（Lagerstroemia）、モモタマナ属（Terminalia）、アカミノキ属（Haematoxylon）、ソバカズラ属（Fallopia）及びカギカズラ属（Uncaria）からなる群より選択される少なくとも１つの植物の加工物を含有する、ホスホジエステラーゼ５活性阻害用組成物を提供する。 The present invention relates to the genus Rubus, Punica, Filipendula, Bayberry, Eugenia, Lagerstroemia, Terminalia, Haematoxylon. ), A composition for inhibiting the activity of phosphodiesterase 5, which comprises a processed product of at least one plant selected from the group consisting of the genus Fallopia (Fallopia) and the genus Uncaria (Uncaria).
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、それぞれ、キイチゴ属、ザクロ属、シモツケソウ属、ヤマモモ属、エウゲニア属、サルスベリ属、モモタマナ属、アカミノキ属、ソバカズラ属、カギカズラ属のいずれかに属する植物が挙げられる。 As raw materials for the processed plant of the plant contained as an active ingredient in the composition of the present invention, the genus Kistrawberry, the genus Pomegranate, the genus Shimotsukesou, the genus Bayberry, the genus Eugenia, the genus Salsberg, the genus Tropical almond, the genus Haematoxylum, the genus Fallopia, and the genus Uncaria, respectively. Examples include plants belonging to any of the genera.
キイチゴ属はバラ科に属し、本発明を制限するものではないが、該属に属する植物としてヒマラヤブラックベリー（Rubus armeniacus Focke）、セイヨウヤブイチゴ（Rubus fruticosus）、アメリカイチゴ（Rubus strigosus）等が例示される。 The genus Rubus belongs to the Rosaceae family and does not limit the present invention, but examples of plants belonging to the genus include Himalayan blackberries (Rubus armeniacus Focke), Rubus fruticosus, and Rubus strigosus. Will be done.
ザクロ属はミソハギ科に属し、本発明を制限するものではないが、該属に属する植物としてザクロ（Punica granatum）等が例示される。 The genus Pomegranate belongs to the Lythraceae family and does not limit the present invention, but examples of plants belonging to the genus include pomegranate (Punica granatum) and the like.
シモツケソウ属はバラ科に属し、本発明を制限するものではないが、該属に属する植物としてセイヨウナツユキソウ（Filipendula ulmaria）等が例示される。 The genus Filipendula belongs to the family Rosaceae and does not limit the present invention, but examples of plants belonging to the genus include Meadowsweet (Filipendula ulmaria).
ヤマモモ属はヤマモモ科に属し、本発明を制限するものではないが、該属に属する植物としてシロコヤマモモ（Myrica cerifera）、ヤマモモ（Myrica rubura）等が例示される。 The genus Bayberry belongs to the family Myricaceae and does not limit the present invention, but examples of plants belonging to the genus include Southern wax myrtle (Myrica cerifera) and Myrica rubura.
エウゲニア属はフトモモ科に属し、本発明を制限するものではないが、該属に属する植物としてタチバナアデク（Eugenia uniflora）、クローブ（Eugenia aromaticum）等が例示される。 The genus Eugenia belongs to the family Myrtaceae and does not limit the present invention, but examples of plants belonging to the genus include Tachibana adec (Eugenia uniflora) and clove (Eugenia aromaticum).
サルスベリ属はミソハギ科に属し、本発明を制限するものではないが、該属に属する植物としてバナバ（Lagerstroemia speciosa）等が例示される。 The genus Crape myrtle belongs to the Lythraceae family and does not limit the present invention, but examples of plants belonging to the genus include banaba (Lagerstroemia speciosa).
モモタマナ属はシクンシ科に属し、本発明を制限するものではないが、該属に属する植物としてモモタマナ（Terminalia catappa）、セイタカミロバラン（Terminalia bellirica）等が例示される。 The genus Momotamana belongs to the family Combretaceae and does not limit the present invention, but examples of plants belonging to the genus include Momotamana (Terminalia catappa) and Seitakamirobaran (Terminalia bellirica).
アカミノキ属はマメ科に属し、本発明を制限するものではないが、該属に属する植物としてアカミノキ（Haematoxylon campechianum）等が例示される。 The genus Haematoxylum belongs to the family Leguminosae and does not limit the present invention, but examples of plants belonging to the genus include logwood (Haematoxylon campechianum).
ソバカズラ属はタデ科に属し、本発明を制限するものではないが、該属に属する植物としてイタドリ（Fallopia japonica）等が例示される。 The genus Fallopia belongs to the family Polygonaceae and does not limit the present invention, but examples of plants belonging to the genus include Japanese knotweed (Fallopia japonica).
カギカズラ属はアカネ科に属し、本発明を制限するものではないが、該属に属する植物としてキャッツクロー（Uncaria guianensis）等が例示される。 The genus Uncaria belongs to the family Rubiaceae and does not limit the present invention, but examples of plants belonging to the genus include cat's claw (Uncaria guianensis).
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。 These may be used alone or in combination of two or more.
これらの植物であれば使用部位は特に限定されないが、葉、茎、果実、花、芽、枝、幹、樹皮、根、花蕾、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。好ましくは葉、茎、果実、樹皮、根、幹、花蕾等が例示され、より好ましくは、キイチゴ属では葉、果実、ザクロ属では果実、シモツケソウ属では葉、茎、ヤマモモ属では樹皮、エウゲニア属では果実、花蕾、サルスベリ属では葉、モモタマナ属では果実、アカミノキ属では幹、ソバカズラ属では茎、葉、カギカズラ属では根、茎、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 these plants are used, the site of use is not particularly limited, but leaves, stems, fruits, flowers, buds, branches, trunks, bark, roots, flower buds, seeds, seed coats, etc. are exemplified and appropriately selected according to each plant. Just do it. Preferred are leaves, stems, fruits, bark, roots, trunks, flower buds and the like, more preferably leaves and fruits in the genus Haematoxylum, fruits in the genus Haematoxylum, leaves and stems in the genus Haematoxylum, bark and genia in the genus Yamamomo. Examples include fruits, flower buds, leaves in the genus Salsberg, fruits in the genus Momotamana, stems in the genus Haematoxylum, stems and leaves in the genus Soba, and roots, stems and leaves in the genus Kagikazura. 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。また、乾燥物中の水分量としては、１０重量％以下が好ましく、８重量％以下がより好ましい。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 freeze drying, etc.). be able to. The water content in the dried product is preferably 10% by weight or less, more preferably 8% by weight or less. 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、更に好ましくは水、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 water, 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、組成物中に前記植物の加工物が含まれていればよく、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重量％より多く含まれていることが例示され、好ましくは０重量％より多く１００重量％未満であることが例示され、より好ましくは０．００１～９９重量％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 product of the plant in the composition of the present invention may be limited as long as the processed product of the plant is contained in the composition, as long as the effect of the present invention can be obtained. In the composition, it is exemplified that the processed product of the plant is contained in an amount of more than 0% by weight in terms of a dry matter, preferably more than 0% by weight and less than 100% by weight, more preferably. Is exemplified by 0.001 to 99% by weight. 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、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（乾燥重量換算として）、好ましくは０．００１～８０００ｍｇ、より好ましくは０．０１～５０００ｍｇ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 body shape, age, symptom, and application of the subject (target animal). It may be appropriately set according to the form, purpose of use, degree of expected effect, and the like. Although not limiting the present invention, the daily dose (intake) of the processed plant is preferably 0.001 to 8000 mg in total (in terms of dry weight) based on an adult weighing 60 kg. More preferably, 0.01 to 5000 mg is exemplified. 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、エアゾール剤等、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, alcoholic beverages, and elixyl agents, powders, granules, fine granules, tablets, rounds, and capsules (capsules). Semi-solid or solid forms such as hard capsules, soft capsules), troches, chewables, gels, creams, pastes, mousses, sheets, and liquid freeze-dried products, as well as aerosols, patches, etc. Various forms such as a happing 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 (lower alcohol such as water, 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 adjusters, surfactants, coating agents, 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.
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が例示される。ヒト以外の哺乳動物としては、ホスホジエステラーゼ５がｃＧＭＰの分解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 and mammals other than humans are exemplified. Examples of mammals other than humans include animals in which phosphodiesterase 5 promotes the degradation of cGMP, 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ホスホジエステラーゼ５（ＰＤＥ５）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ＰＤＥ５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、ＰＤＥ５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、ＰＤＥ５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 phosphodiesterase 5 (PDE5) 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 PDE5 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 PDE5 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 PDE5 activity, which comprises using the processed product of the plant.
このように本発明の組成物によれば、ＰＤＥ５の活性を阻害できる。このことから、本発明によればｃＧＭＰの分解を抑制することができ、ＰＤＥ５の活性や局所血流低下に起因する疾患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 PDE5 can be inhibited. From this, according to the present invention, the decomposition of cGMP can be suppressed, and the composition of the present invention can be used for the purpose of preventing or ameliorating diseases caused by PDE5 activity or decreased local blood flow.
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、陰茎***機能、下部尿路機能障害、前立腺肥大、肺高血圧症等の予防または改善に有用である。例えば、ＰＤＥ５阻害作用により平滑筋が弛緩し、これにより陰茎海綿体への血流を増加させることで陰茎***機能の改善を図ることができ、泌尿器系への血流を増加させることで下部尿路障害の改善を図ることができ、前立腺や尿道の血流を増加させることで前立腺肥大の緩和を図ることができ、肺組織への血流を増加させることで肺動脈圧の低下を図ることができる。 Therefore, the composition of the present invention does not limit the present invention, but is useful for preventing or ameliorating penile erection function, lower urinary tract dysfunction, benign prostatic hyperplasia, pulmonary hypertension and the like. For example, PDE5 inhibitory action relaxes smooth muscle, which can improve penile erectile function by increasing blood flow to the corpus cavernosum, and lower urinary system by increasing blood flow to the urinary system. It is possible to improve tract disorders, alleviate prostate enlargement by increasing blood flow in the prostate and urethra, and reduce pulmonary arterial pressure by increasing blood flow to lung tissue. can.
このことから、本発明の組成物はまた、男性機能が気になる対象者、排尿機能が気になる対象者等に好ましく適用することができる。 From this, the composition of the present invention can also be preferably applied to a subject who is concerned about male function, a subject who is concerned about urination function, and the like.
また、本発明の組成物は、ＰＤＥ５活性阻害薬、陰茎***機能（不全）治療薬、下部尿路機能障害治療薬、前立腺肥大治療薬、肺高血圧症治療薬（特に肺動脈性肺高血圧症）等としても使用できる Further, the composition of the present invention includes a PDE5 activity inhibitor, a penis erectile function (deficiency) therapeutic agent, a lower urinary tract dysfunction therapeutic agent, a prostatic hypertrophy therapeutic agent, a pulmonary hypertension therapeutic agent (particularly pulmonary arterial hypertension) and the like. Can also be used as
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.
試験例１
１．植物の加工物
表１に示す植物を原料として、各植物の抽出物を準備した。具体的には、実施例１、５、９及び１０については次の手順に従い抽出物を調製し、その他の実施例については市販品を用いた。
Test Example 1
1. 1. Processed Plants Extracts of each plant were prepared using the plants shown in Table 1 as raw materials. Specifically, extracts were prepared according to the following procedure for Examples 1, 5, 9 and 10, and commercially available products were used for the other Examples.
実施例１：ヒマラヤブラックベリー
ヒマラヤブラックベリーの葉の乾燥物50ｇを破砕し、水を1000 ml添加して80℃、1時間で抽出処理を実施した。得られた抽出物をミラクロス（メルク・ミリポア社製）にて濾過し、不溶性成分を除去した濾液を凍結乾燥することで、ヒマラヤブラックベリー抽出物（抽出乾燥物7.9 g）を得た。
Example 1: Himalayan blackberry 50 g of a dried Himalayan blackberry leaf was crushed, 1000 ml of water was added, and an extraction treatment was carried out at 80 ° C. for 1 hour. The obtained extract was filtered through Miracross (manufactured by Merck Millipore), and the filtrate from which insoluble components had been removed was freeze-dried to obtain a Himalayan blackberry extract (7.9 g of dried extract).
実施例２：セイヨウヤブイチゴ
セイヨウヤブイチゴの葉の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、セイヨウヤブイチゴ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。
Example 2: Extract of leaves of Seiyo Yabu Strawberry (custom-made, powder dried product manufactured by Nippon Shinyaku Co., Ltd.) was used. This extract was obtained by crushing dried leaves of strawberry leaves, adding methanol for extraction, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components had been removed. be.
実施例３：アメリカイチゴ
アメリカイチゴの葉及び果実の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、アメリカイチゴの葉及び果実の乾燥物を破砕し、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。
Example 3: American Strawberry An extract of leaves and fruits of American strawberry (custom-made, powder dried product manufactured by Nippon Shinyaku Co., Ltd.) was used. This extract was obtained by crushing dried American strawberry leaves and fruits, adding methanol for extraction, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components had been removed. Is.
実施例４：ザクロ
ザクロの果皮の抽出物（商品名ザクロ果皮エキス末、香栄興業製、粉末乾燥物）を用いた。
Example 4: An extract of pomegranate peel (trade name: pomegranate peel extract powder, manufactured by Koei Kogyo Co., Ltd., dried powder) was used.
実施例５：セイヨウナツユキソウ
セイヨウナツユキソウの茎及び葉の乾燥物40ｇを破砕し、水を1000ml添加して80℃、1時間で抽出処理を実施した。得られた抽出物をミラクロス（メルク・ミリポア社製）にて濾過し、不溶性成分を除去した濾液を凍結乾燥することで、セイヨウナツユキソウ抽出物（抽出乾燥物9.9 g）を得た。
Example 5: Meadowsweet Meadowsweet 40 g of dried stems and leaves of Meadowsweet was crushed, 1000 ml of water was added, and extraction treatment was carried out at 80 ° C. for 1 hour. The obtained extract was filtered through Miracross (manufactured by Merck Millipore), and the filtrate from which insoluble components had been removed was freeze-dried to obtain an extract of Meadowsweet (9.9 g of dried extract).
実施例６：シロコヤマモモ
シロコヤマモモの樹皮の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、シロコヤマモモの樹皮の乾燥物を破砕し、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。
Example 6: Extract of the bark of Southern wax myrtle (custom-made, powder-dried product manufactured by Nippon Shinyaku Co., Ltd.) was used. This extract was obtained by crushing the dried bark of Southern wax myrtle, adding methanol to extract it, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components had been removed. ..
実施例７：ヤマモモ
ヤマモモの樹皮の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、ヤマモモの樹皮の乾燥物を破砕し、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。
Example 7: Extract of bayberry bark (custom-made, powder dried product manufactured by Nippon Shinyaku Co., Ltd.) was used. This extract was obtained by crushing the dried bark of bayberry, adding methanol to extract the extract, filtering the obtained extract, and freeze-drying the filtrate from which the insoluble components had been removed.
実施例８：タチバナアデク
タチバナアデクの果実の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、タチバナアデクの果実の乾燥物を破砕し、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。
Example 8: Tachibana Adecta A fruit extract of Tachibana Adek (custom-made, powder-dried product manufactured by Nippon Shinyaku Co., Ltd.) was used. This extract was obtained by crushing the dried fruit of Boxleaf Eugenia, adding methanol to extract it, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components had been removed. ..
実施例９：クローブ
クローブの花蕾の乾燥物50ｇを破砕し、水を1000ml添加して80℃、 1時間で抽出処理を実施した。得られた抽出物をミラクロス（メルク・ミリポア社製）にて濾過し、不溶性成分を除去した濾液を凍結乾燥することで、クローブ抽出物（抽出乾燥物10.1 g）を得た。
Example 9: 50 g of dried clove clove flower buds was crushed, 1000 ml of water was added, and extraction treatment was carried out at 80 ° C. for 1 hour. The obtained extract was filtered through Miracross (manufactured by Merck Millipore), and the filtrate from which insoluble components had been removed was freeze-dried to obtain a clove extract (extracted dried product 10.1 g).
実施例１０：バナバ
バナバ葉の乾燥物60ｇを破砕し、50質量％エタノール（水とエタノールとの質量比１：１）を900ml添加して25℃、12時間で抽出処理を実施した。得られた抽出物をミラクロス（メルク・ミリポア社製）にて濾過し、不溶性成分を除去した濾液からエタノールを留去した後、凍結乾燥することで、バナバ抽出物（抽出乾燥物8.9 g）を得た。
Example 10: 60 g of dried banaba banaba leaves was crushed, 900 ml of 50% by mass ethanol (mass ratio of water to ethanol 1: 1) was added, and extraction treatment was carried out at 25 ° C. for 12 hours. The obtained extract is filtered through Miracross (manufactured by Merck Millipore), ethanol is distilled off from the filtrate from which insoluble components have been removed, and then freeze-dried to obtain a banaba extract (extracted dried product 8.9 g). Obtained.
実施例１１：モモタマナ
モモタマナの果実の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、モモタマナの果実の乾燥物を破砕し、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。
Example 11: Indian -almond Extract of fruit of Indian-almond (custom-made, powder-dried product manufactured by Nippon Shinyaku Co., Ltd.) was used. This extract was obtained by crushing a dried fruit of Indian-almond, adding methanol to extract it, filtering the obtained extract, and freeze-drying a filtrate from which insoluble components had been removed.
実施例１２：セイタカミロバラン
セイタカミロバランの果実の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、セイタカミロバランの果実の乾燥物を破砕し、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。
Example 12: Seitakamirobaran An extract of the fruit of Seitakamirobaran (custom-made, powder-dried product manufactured by Nippon Shinyaku Co., Ltd.) was used. This extract was obtained by crushing the dried fruit of Seitakamirobaran, adding methanol to extract it, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components had been removed. be.
実施例１３：アカミノキ
アカミノキの幹の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、アカミノキの幹の乾燥物を破砕し、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。
Example 13: Akaminoki An extract of Akaminoki stem (custom-made, powder dried product manufactured by Nippon Shinyaku Co., Ltd.) was used. This extract was obtained by crushing a dried logwood stem, adding methanol for extraction, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components had been removed.
実施例１４：イタドリ
イタドリの茎及び葉の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、イタドリの茎及び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。
Example 14: Japanese knotweed Japanese knotweed stem and leaf extract (custom-made, powder dried product manufactured by Nippon Shinyaku Co., Ltd.) was used. This extract was obtained by crushing dried Japanese knotweed stems and leaves, adding methanol for extraction, filtering the obtained extract, and lyophilizing the filtrate from which insoluble components had been removed. be.
実施例１５：キャッツクロー
キャッツクローの根、茎及び葉の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、キャッツクローの根、茎及び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。
Example 15: Cat 's claw An extract of roots, stems and leaves of cat's claw (custom-made, powder-dried product manufactured by Nippon Shinyaku Co., Ltd.) was used. This extract is obtained by crushing dried roots, stems and leaves of cat's claw, adding methanol for extraction, filtering the obtained extract, and lyophilizing the filtrate from which insoluble components have been removed. It is a thing.
比較例：クロショウガ
クロショウガの根茎の抽出物（商品名黒ショウガエキス－Ｐ、オリザ油化製、粉末乾燥物）を用いた。クロショウガは、従来、ホスホジエステラーゼ(PDE)に対して阻害作用を有していると知られている植物である。
Comparative Example: Black Ginger Rhizome Extract (trade name: Black Ginger Extract-P, Oryza Oil Chemicals, powder dried product) was used. Black ginger is a plant conventionally known to have an inhibitory effect on phosphodiesterase (PDE).
２．ホスホジエステラーゼ(PDE)5阻害活性の測定
前記１．で準備した各抽出物の、PDE5に対する阻害活性を測定した（n=3）。本測定において、PDE5A Assay Kit (♯60350)（BPSバイオサイエンス社製）、96wellプレート、ピペットマン、PerkinElmer EnVision 2102 Multilabel Reader（パーキンエルマー社製）を用い、キットに付帯の手順書に従い、阻害活性を測定した。
2. 2. Measurement of phosphodiesterase (PDE) 5 inhibitory activity 1. The inhibitory activity against PDE5 of each extract prepared in 1 was measured (n = 3). In this measurement, the inhibitory activity was measured using the PDE5A Assay Kit (# 60350) (manufactured by BPS Bioscience), 96well plate, Pipetman, and PerkinElmer EnVision 2102 Multilabel Reader (manufactured by PerkinElmer) according to the procedure manual attached to the kit. bottom.
具体的には、希釈調製したFAM-Cyclic-3’, 5’-GMPを25μLずつ各ウェルに添加した。「Blank」に25μLずつPDEバッファーを添加した。次いで、前述のように準備した抽出物600mgとジメチルスルホキシド20 mLとを混合して抽出物含有溶液を得た後、抽出物含有溶液5μLと滅菌水495μLを混合してサンプル溶液（抽出物濃度300μg/mL）とした。サンプル溶液（「Test」のウェル）またはサンプル溶媒（「Blank」、「Substrate control」、「Positive control」のウェル）を、各ウェルに5μL添加した。次いで、「Blank」と「Substrate control」のウェルに20μLずつPDEアッセイバッファーを添加した。希釈調製したPDE5Aを「Test」、「Positive control」のウェルに20 μLずつ添加した（200 pg/反応ウェル）。 25℃で1時間反応させた。希釈調製したBinding agentを100μLずつ各ウェルに添加し、25℃で30分間強く振とうしながら反応させた。プレートリーダーで蛍光偏光を測定した（Excitation：475-495 nm、Emission：518-538 nm）。「Blank」値をそれぞれの測定値から減じ、蛍光偏光値を算出した。また、IC50測定にはサンプル溶液の濃度を段階的に減少させて阻害率が50%になるサンプル濃度を求めた。 Specifically, 25 μL of diluted FAM-Cyclic-3'and 5'-GMP were added to each well. 25 μL of PDE buffer was added to “Blank”. Next, 600 mg of the extract prepared as described above and 20 mL of dimethyl sulfoxide were mixed to obtain an extract-containing solution, and then 5 μL of the extract-containing solution and 495 μL of sterile water were mixed to obtain a sample solution (extract concentration 300 μg). / mL). 5 μL of sample solution (“Test” wells) or sample solvent (“Blank”, “Substrate control”, “Positive control” wells) was added to each well. Then, 20 μL of PDE assay buffer was added to each of the “Blank” and “Substrate control” wells. 20 μL of diluted PDE5A was added to each of the “Test” and “Positive control” wells (200 pg / reaction well). The reaction was carried out at 25 ° C. for 1 hour. 100 μL of the diluted Binder was added to each well, and the mixture was reacted at 25 ° C. for 30 minutes with vigorous shaking. Fluorescence polarization was measured with a plate reader (Excitation: 475-495 nm, Emission: 518-538 nm). The "Blank" value was subtracted from each measured value to calculate the fluorescence polarization value. In addition, for IC50 measurement, the concentration of the sample solution was gradually reduced to determine the sample concentration at which the inhibition rate was 50%.
３．結果
結果を表１に示す。表１にはIC50値を示す。
3. 3. Results The results are shown in Table 1. Table 1 shows the IC50 values.
表１から明らかなように、クロショウガでは、そのIC50値（μg/mL）は50を上回った。これに対して、実施例１～１５に示す植物の抽出物ではいずれも一層優れたPDE5活性阻害作用が認められ、これはクロショウガの阻害作用を大きく上回るものであった。 As is clear from Table 1, in black ginger, its IC50 value (μg / mL) exceeded 50. On the other hand, in all of the plant extracts shown in Examples 1 to 15, a more excellent PDE5 activity inhibitory action was observed, which greatly exceeded the inhibitory action of black ginger.
このことから、PDEに対して活性阻害作用を有していることが従来知られている植物であるクロショウガよりも、前記植物の加工物によれば、より効果的にPDE5の活性を阻害できることが確認された。 From this, the processed product of the plant can more effectively inhibit the activity of PDE5 than the black ginger, which is a plant conventionally known to have an activity inhibitory effect on PDE. Was confirmed.
試験例２
１．測定手順
前記試験例で準備した実施例１、４、５及び１０の抽出物、比較例の抽出物、ならびに対照として水を用いて、ラット組織中の環状グアノシン一リン酸（cGMP）量を測定した。
Test Example 2
1. 1. Measurement procedure Using the extracts of Examples 1, 4, 5 and 10 prepared in the above test example, the extracts of Comparative Examples, and water as a control, the amount of cyclic guanosine monophosphate (cGMP) in rat tissue was measured. bottom.
本測定には、SD系雄ラット（体重約250g/匹）、cGMP ELISA kit（ADI-900-014、エンゾライフサイエンス社製）、PerkinElmer EnVision 2102 Multilabel Reader（パーキンエルマー社製）を用いた。 For this measurement, SD male rats (body weight about 250 g / animal), cGMP ELISA kit (ADI-900-014, manufactured by Enzo Life Science), and PerkinElmer EnVision 2102 Multilabel Reader (manufactured by PerkinElmer) were used.
具体的には、前記抽出物2gと蒸留水8mLとを混合し、前記抽出物含有投与液（500mg/2mL/kg体重）を各投与の直前に調製した。得られた投与液を、試験開始0時間及び24時間後に、ゾンデでラットの胃内に投与した（n=8）。試験開始25時間後に麻酔下でラットの陰茎を摘出し、これを液体窒素を用いて凍結保存した。cGMP ELISA kitに記載されている方法に従って、陰茎組織中のcGMP量を測定した。なお、対照として、抽出物含有投与液に代えて蒸留水を用いる以外は、同様にして胃内に投与し、陰茎組織中のcGMP量を測定した。 Specifically, 2 g of the extract and 8 mL of distilled water were mixed, and the extract-containing administration solution (500 mg / 2 mL / kg body weight) was prepared immediately before each administration. The obtained dosage solution was administered into the stomach of rats by sonde 0 hours and 24 hours after the start of the test (n = 8). Twenty-five hours after the start of the test, the penis of the rat was excised under anesthesia and cryopreserved using liquid nitrogen. The amount of cGMP in the penile tissue was measured according to the method described in the cGMP ELISA kit. As a control, it was administered intragastrically in the same manner except that distilled water was used instead of the extract-containing administration solution, and the amount of cGMP in the penile tissue was measured.
２．結果
結果を表２に示す。
2. 2. Results The results are shown in Table 2.
表２から明らかなように、クロショウガ投与時のcGMP量は、蒸留水投与時のcGMP量を多少上回る程度であった。これに対して、実施例１、４、５及び１０の抽出物投与時のcGMP量は、クロショウガ投与時の２倍程度か２倍を大きく上回った。 As is clear from Table 2, the amount of cGMP at the time of administration of black ginger was slightly higher than the amount of cGMP at the time of administration of distilled water. On the other hand, the amount of cGMP at the time of administration of the extracts of Examples 1, 4, 5 and 10 was about twice or much higher than that at the time of administration of black ginger.
このように、実施例１、４、５及び１０の加工物において得られる値は、クロショウガにおいて得られる値を上回ったことから、実施例１、４、５及び１０の加工物によれば、ＰＤＥ５の活性や局所血流低下に起因する疾患をより効果的に予防または改善できることが確認された。 As described above, since the values obtained in the workpieces of Examples 1, 4, 5 and 10 exceeded the values obtained in the black ginger, according to the workpieces of Examples 1, 4, 5 and 10. It was confirmed that diseases caused by PDE5 activity and decreased local blood flow can be prevented or ameliorated more effectively.
また、前記試験例１の結果から明らかなように、PDE5の活性阻害作用の点で、実施例２、３、６～９及び１１～１５の加工物はクロショウガを大きく上回っており、このことから、実施例２、３、６～９及び１１～１５の加工物も、PDE5活性や局所血流低下に起因する疾患をより効果的に予防または改善できることが確認された。 Further, as is clear from the results of Test Example 1, the processed products of Examples 2, 3, 6 to 9 and 11 to 15 greatly exceed the black ginger in terms of the activity inhibitory action of PDE5. It was confirmed that the processed products of Examples 2, 3, 6 to 9 and 11 to 15 can also more effectively prevent or ameliorate diseases caused by PDE5 activity and decreased local blood flow.
Claims (3)
該溶媒が、水、メタノール、エタノール、イソプロパノール、プロピレングリコール及び１，３－ブチレングリコールからなる群より選択される少なくとも１種であり、
該植物が、ヒマラヤブラックベリー（Rubus armeniacus Focke）、セイヨウヤブイチゴ（Rubus fruticosus）及びアメリカイチゴ（Rubus strigosus）からなる群より選択される少なくとも１つである、
ホスホジエステラーゼ５活性阻害用組成物。 Contains solvent extracts of plants belonging to the genus Rubus
The solvent is at least one selected from the group consisting of water, methanol, ethanol, isopropanol, propylene glycol and 1,3-butylene glycol.
The plant is at least one selected from the group consisting of Himalayan blackberries (Rubus armeniacus Focke), Rubus fruticosus and Rubus strigosus.
A composition for inhibiting the activity of phosphodiesterase 5.
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| CN202110993090.9A CN113559159A (en) | 2016-12-28 | 2017-12-22 | Composition for inhibiting type 5 phosphodiesterase activity |
| PCT/JP2017/046245 WO2018123908A1 (en) | 2016-12-28 | 2017-12-22 | Composition for inhibiting phosphodiesterase-5 activity |
| CN201780081426.6A CN110167571A (en) | 2016-12-28 | 2017-12-22 | Composition is used in the inhibition of 5 type phosphodiesterase activities |
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| FR3122990A1 (en) | 2021-05-20 | 2022-11-25 | Patrinove | Extract of plant with crassulacean acid metabolism for use in the treatment of erectile dysfunction |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003183122A (en) | 2001-12-21 | 2003-07-03 | Ichimaru Pharcos Co Ltd | Agent for inhibiting activity of collagenase |
| KR20140101520A (en) | 2013-02-11 | 2014-08-20 | 주식회사한국전통의학연구소 | A pharmaceutical composition for improving generative of male and treating infertility |
| WO2014126269A1 (en) | 2013-02-12 | 2014-08-21 | 주식회사 한국전통의학연구소 | Pharmaceutical composition for improving male sexual function and for treating infertility |
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| KR100462173B1 (en) * | 2004-06-08 | 2004-12-16 | 안국약품 주식회사 | A composition for prevention and treatment of urinary incontinence |
| ITMI20050068A1 (en) * | 2005-01-21 | 2005-04-22 | Ignazio Abbruzzo | PASTA DENTIFRICIA COMPOSED MAINLY BY A COMMON PLANT RUBUS FRUTICOSUS WHICH PARTS OF IT CONTAIN AN ACTIVE PRINCIPLE THAT FIGHTS THE DENTAL CARIES GIVES THE HEALTH OF THE GUMS AND THE CLEANING OF THE TEETH |
| CN103520618B (en) * | 2013-10-21 | 2015-08-26 | 孟庆坤 | A kind of pharmaceutical composition for the treatment of erection disturbance and preparation method thereof and pharmaceutical applications |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003183122A (en) | 2001-12-21 | 2003-07-03 | Ichimaru Pharcos Co Ltd | Agent for inhibiting activity of collagenase |
| KR20140101520A (en) | 2013-02-11 | 2014-08-20 | 주식회사한국전통의학연구소 | A pharmaceutical composition for improving generative of male and treating infertility |
| WO2014126269A1 (en) | 2013-02-12 | 2014-08-21 | 주식회사 한국전통의학연구소 | Pharmaceutical composition for improving male sexual function and for treating infertility |
Non-Patent Citations (2)
| Title |
|---|
| Can J Plant Sci., 2015, Vol.95, p.557-570 |
| Phytother Res., 2011, Vol.25, p.1046-1053 |
Also Published As
| Publication number | Publication date |
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| JP2018108946A (en) | 2018-07-12 |
| WO2018123908A1 (en) | 2018-07-05 |
| CN110167571A (en) | 2019-08-23 |
| CN113559159A (en) | 2021-10-29 |
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