JP2014144942A - Preventive or improver for overactive bladder - Google Patents
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Abstract
Description
本発明は、過活動膀胱の予防又は改善剤に関する。 The present invention relates to an agent for preventing or improving overactive bladder.
過活動膀胱(overactive bladder: OAB)は泌尿器系の疾患で、頻尿、尿意切迫感、切迫性尿失禁といった症状を伴う。これらの症状は、日常生活に大きな支障を与え生活の質を低下させる。その程度は、糖尿病と同程度とも言われている。有病率は加齢に伴い上昇し、超高齢化社会の日本では40歳以上の罹患者は約810万人にものぼると推定されている。
近年、過活動膀胱の原因として、膀胱の求心性神経活動の亢進が指摘されている。求心性神経活動の亢進は、蓄尿に伴う膀胱の伸展刺激を受けて膀胱上皮細胞から放出されるアデノシン三リン酸(adenosine triphosphate:以下ATPと略記する)やアセチルコリン(acetylcholine)等の神経伝達物質により起こると考えられている。ヒトは加齢に伴い膀胱上皮細胞から放出されるATP量が増加すること、及び過活動膀胱患者では膀胱伸展時のATP放出量が増大することが報告されている(非特許文献1参照)。また、ラットの膀胱にATPを投与すると、排尿筋過活動が誘発され、排尿間隔が短縮することも報告されている(非特許文献2参照)。
Overactive bladder (OAB) is a urinary disease with symptoms such as frequent urination, urgency and urge incontinence. These symptoms can greatly interfere with daily life and reduce the quality of life. It is said that the degree is the same as diabetes. The prevalence increases with aging, and it is estimated that approximately 8.1 million affected people in Japan, a super-aging society, are over 40 years old.
In recent years, increased afferent nerve activity of the bladder has been pointed out as a cause of overactive bladder. Enhancement of afferent nerve activity is caused by neurotransmitters such as adenosine triphosphate (ATP) and acetylcholine, which are released from bladder epithelial cells in response to bladder extension stimulation accompanying urine storage. It is thought to happen. It has been reported that the amount of ATP released from bladder epithelial cells increases with aging in humans, and that the amount of ATP released during bladder extension increases in overactive bladder patients (see Non-Patent Document 1). It has also been reported that when ATP is administered to the rat bladder, detrusor overactivity is induced and the urination interval is shortened (see Non-Patent Document 2).
現在、過活動膀胱の薬物治療には、抗コリン薬が用いられている。抗コリン薬は、膀胱の排尿筋の収縮を促進するアセチルコリンの作用を阻害する。しかし、抗コリン薬は、患者によっては明確な症状改善効果が見られない、副作用として口渇や便秘等の症状を呈する等、問題点も多く、より効果的な予防・改善方法が望まれている。 Currently, anticholinergic drugs are used for drug treatment of overactive bladder. Anticholinergic drugs inhibit the action of acetylcholine, which promotes contraction of the bladder detrusor muscle. However, anticholinergic drugs do not have a clear symptom-improving effect depending on patients, and there are many problems such as symptoms such as dry mouth and constipation as side effects, and more effective prevention and improvement methods are desired. Yes.
抗コリン薬は、放出されたアセチルコリンが膀胱平滑筋の受容体へ結合するのを阻害するが、これはいわゆる対症療法であり、効果の点から十分な治療法とは言い難い。また、抗コリン薬には、上述のような副作用もある。これに対し、過活動膀胱の原因である膀胱上皮細胞からの過度のATP放出を抑制することができれば、過活動膀胱の原因療法となり得る。 Anticholinergic drugs inhibit the release of released acetylcholine from binding to the receptors of bladder smooth muscle, but this is a so-called symptomatic treatment, and it is difficult to say that it is a sufficient treatment from the viewpoint of effectiveness. Anticholinergic drugs also have side effects as described above. On the other hand, if excessive ATP release from bladder epithelial cells, which is the cause of overactive bladder, can be suppressed, it can be a causative therapy for overactive bladder.
本発明は、膀胱上皮細胞からの異常なATP放出を抑制しうる、過活動膀胱の予防又は改善剤を提供することを課題とする。また、本発明は、過活動膀胱の症状、すなわち頻尿、尿意切迫感又は切迫性尿失禁の予防又は改善剤を提供することを課題とする。さらに、本発明は、膀胱上皮細胞からのATP放出を抑制する、ATP放出抑制剤を提供することを課題とする。 An object of the present invention is to provide an agent for preventing or improving overactive bladder, which can suppress abnormal ATP release from bladder epithelial cells. Another object of the present invention is to provide a preventive or ameliorating agent for symptoms of overactive bladder, that is, frequent urination, urgency, or urge urinary incontinence. Furthermore, an object of the present invention is to provide an ATP release inhibitor that suppresses ATP release from bladder epithelial cells.
本発明者らは上記課題に鑑み、過活動膀胱の原因となる膀胱上皮細胞からのATP放出を抑制しうる物質について鋭意検討を行った。その結果、特定の化合物にATP放出を抑制する作用があり、過活動膀胱の予防又は改善に有用であることを見出した。本発明はこれらの知見に基づいて完成するに至ったものである。 In view of the above problems, the present inventors have conducted intensive studies on substances that can suppress ATP release from bladder epithelial cells that cause overactive bladder. As a result, the present inventors have found that a specific compound has an action of suppressing ATP release and is useful for prevention or improvement of overactive bladder. The present invention has been completed based on these findings.
本発明は、下記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物を有効成分とする、過活動膀胱の予防又は改善剤に関する。 The present invention relates to an agent for preventing or improving overactive bladder, comprising as an active ingredient at least one compound selected from the group consisting of compounds represented by the following formulas (1) to (4).
また、本発明は、前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物を有効成分とする、ATP放出抑制剤に関する。
さらに、本発明は、前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物を有効成分とする、頻尿の予防又は改善剤に関する。
The present invention also relates to an ATP release inhibitor comprising as an active ingredient at least one compound selected from the group consisting of compounds represented by the formulas (1) to (4).
Furthermore, the present invention relates to a preventive or ameliorating agent for pollakiuria comprising as an active ingredient at least one compound selected from the group consisting of the compounds represented by the formulas (1) to (4).
本発明の過活動膀胱の予防又は改善剤は、膀胱上皮細胞からのATP放出を抑制し、過活動膀胱とそれに伴う症状である頻尿、尿意切迫感、切迫性尿失禁を予防又は改善することができる。また、本発明のATP放出抑制剤は、膀胱上皮細胞からのATPの放出を抑制することができる。 The agent for preventing or improving overactive bladder of the present invention suppresses ATP release from bladder epithelial cells, and prevents or improves overactive bladder and accompanying symptoms such as frequent urination, urgency, and urge urinary incontinence. Can do. Moreover, the ATP release inhibitor of the present invention can suppress the release of ATP from bladder epithelial cells.
本発明の過活動膀胱の予防又は改善剤、頻尿の予防又は改善剤(以下、これらをまとめて「本発明の予防・改善剤」ともいう)、及びATP放出抑制剤は、前記式(1)〜(4)のいずれかで表される化合物からなる群より選ばれる少なくとも1種の化合物を有効成分とする。 The agent for preventing or improving overactive bladder of the present invention, the agent for preventing or improving frequent urination (hereinafter collectively referred to as “the agent for preventing or improving the present invention”), and the ATP release inhibitor are those represented by the formula (1). ) To (4), at least one compound selected from the group consisting of compounds represented by any one of the compounds represented by any of (4) is used as an active ingredient.
式(1)で表される化合物は、リナロールである。式(1)で表される化合物には、光学異性体が存在する(Chirality,2010 Jan,22(1),110-9参照)。本発明において、式(1)で表される化合物にはこれらの異性体が包含され、各異性体を単独又は混合して用いることができる。 The compound represented by Formula (1) is linalool. The compound represented by the formula (1) has an optical isomer (see Chirality, 2010 Jan, 22 (1), 110-9). In the present invention, the compound represented by the formula (1) includes these isomers, and each isomer can be used alone or in combination.
式(2)で表される化合物は、リナロールオキシドである。式(2)で表される化合物には、光学異性体が存在する(Chirality,2010 Jan,22(1),110-9参照)。また、式(2)で表される化合物には、下記に示す構造異性体が存在する。本発明において、式(2)で表される化合物にはこれらの異性体が包含され、各異性体を単独又は混合して用いることができる。 The compound represented by the formula (2) is linalool oxide. The compound represented by the formula (2) has an optical isomer (see Chirality, 2010 Jan, 22 (1), 110-9). Moreover, the structural isomer shown below exists in the compound represented by Formula (2). In the present invention, the compound represented by the formula (2) includes these isomers, and each isomer can be used alone or in combination.
式(3)で表される化合物は、ミルセンである。 The compound represented by the formula (3) is myrcene.
式(4)で表される化合物は、ボルネオールである。式(4)で表される化合物には、光学異性体が存在する(Biochem. Pharmacol.,2005 Apr 1,69(7),1101-11参照)。本発明において、式(4)で表される化合物にはこれらの異性体が包含され、各異性体を単独又は混合して用いることができる。 The compound represented by the formula (4) is borneol. The compound represented by formula (4) has an optical isomer (see Biochem. Pharmacol., 2005 Apr 1, 69 (7), 1101-11). In the present invention, the compound represented by the formula (4) includes these isomers, and each isomer can be used alone or in combination.
前記式(1)〜(4)で表される化合物の製造方法に特に制限はなく、通常の有機化学的合成により得ることもできるし、天然物由来の材料から抽出や精製等したものであってもよい。また、試薬として市販されているものを式(1)〜(4)で表される化合物として用いることもできる。
式(1)で表される化合物は、例えば、香料化学総覧II(廣川書店、1980年、P541)に記載の方法を参考に、メチルヘプテノンにアセチレンを、ナトリウムアミド(NaNH2)存在下で縮合させてデヒドロリナロールとし、これをエーテル溶液中、金属ナトリウムで還元することにより得られる。
式(2)で表される化合物は、例えば、香料化学総覧II(廣川書店、1980年、P695)に記載の方法を参考に、リナロールを過モノフタル酸などの有機過酸化物で酸化し、生成物を加熱することにより得られる。この方法では、まず式(2)で現されるリナロールモノエポキサイドが生成し、異性化により上記4つのフラノイド型又はピラノイド型の異性体が単離される。
There is no restriction | limiting in particular in the manufacturing method of the compound represented by said Formula (1)-(4), It can obtain by a normal organic chemical synthesis, It was extracted, refine | purified, etc. from the material derived from a natural product. May be. Moreover, what is marketed as a reagent can also be used as a compound represented by Formula (1)-(4).
The compound represented by the formula (1) is obtained by, for example, condensing acetylene with methylheptenone in the presence of sodium amide (NaNH 2 ) with reference to the method described in Perfume Chemical Directory II (Yodogawa Shoten, 1980, P541). Dehydrolinalool, which is obtained by reduction with sodium metal in an ether solution.
The compound represented by the formula (2) is produced by oxidizing linalool with an organic peroxide such as permonophthalic acid with reference to the method described in, for example, Perfume Chemical Directory II (Yodogawa Shoten, 1980, P695). It is obtained by heating the product. In this method, first, linalool monoepoxide represented by the formula (2) is produced, and the four furanoid or pyranoid isomers are isolated by isomerization.
式(3)で表される化合物は、例えば、香料化学総覧II(廣川書店、1980年、P395)に記載の方法を参考に、リナロールを銅触媒上、130〜140℃で通過させて脱水することにより得られる。
式(4)で表される化合物は、例えば、香料化学総覧II(廣川書店、1980年、P605)に記載の方法を参考に、ショウノウを金属ナトリウムとアルコールで還元することにより得られる。
The compound represented by the formula (3) is dehydrated by passing linalool over a copper catalyst at 130 to 140 ° C. with reference to the method described in, for example, Perfume Chemical Directory II (Yodogawa Shoten, 1980, P395). Can be obtained.
The compound represented by the formula (4) can be obtained, for example, by reducing camphor with sodium metal and alcohol with reference to the method described in Perfume Chemical Directory II (Yodogawa Shoten, 1980, P605).
本発明の予防・改善剤及びATP放出抑制剤には、前記式(1)〜(4)の化合物のいずれかを単独で用いてもよく、2種以上混合して用いてもよい。 In the preventive / ameliorating agent and ATP release inhibitor of the present invention, any one of the compounds of the above formulas (1) to (4) may be used alone, or two or more of them may be used in combination.
前述のように、過活動膀胱患者では膀胱伸展時のATP放出量が増大していること、ラットの膀胱にATPを投与すると、排尿筋過活動が誘発され排尿間隔が短縮すること、が報告されている。さらに、ATP受容体(P2X3)のアンタゴニストをラット静脈内へ投与すると、排尿間隔が延長されるとの報告もなされている(J. Chin. Med. Assoc.,2007年,第70巻,p.439-444)。これらの報告から、過活動膀胱患者に見られる膀胱伸展時のATP放出量の増大を抑制することで、過活動膀胱及びその症状である頻尿、尿意切迫感、切迫性尿失禁を予防・改善し得ると考えられる。
後記実施例でも示すように、前記式(1)〜(4)の化合物は、膀胱の伸展刺激による膀胱上皮細胞からのATP放出を抑制する作用を有する。そのため、これらの化合物は、膀胱上皮細胞からのATPの放出を抑制し、過活動膀胱及びその症状である頻尿、尿意切迫感、切迫性尿失禁を予防・改善するために使用することができる。
上記使用は、治療的使用(即ち医療行為)であっても非治療的使用(非医療的な行為)であってもよい。また、上記使用の対象は、ヒト、非ヒト動物、又はそれらに由来する検体であり得る。なお、前記「非治療的」とは、医療行為、すなわち治療による人体への処理行為を含まない概念である。
As described above, it has been reported that in patients with overactive bladder, the amount of ATP released during bladder extension is increased, and when ATP is administered to the rat bladder, detrusor overactivity is induced and the urination interval is shortened. ing. Furthermore, it has been reported that when an ATP receptor (P2X3) antagonist is administered intravenously into rats, the micturition interval is prolonged (J. Chin. Med. Assoc., 2007, Vol. 70, p. 50). 439-444). From these reports, it is possible to prevent and improve overactive bladder and its symptoms such as frequent urination, urinary urgency, and urge urinary incontinence by suppressing the increase in ATP release during bladder extension in patients with overactive bladder. It is considered possible.
As will be shown in Examples described later, the compounds of the formulas (1) to (4) have an action of suppressing ATP release from bladder epithelial cells due to bladder extension stimulation. Therefore, these compounds can be used to suppress ATP release from bladder epithelial cells, and to prevent and improve overactive bladder and its symptoms such as frequent urination, urgency, and urge urinary incontinence. .
The use may be a therapeutic use (ie medical practice) or a non-therapeutic use (non-medical practice). Moreover, the subject of the use can be a human, a non-human animal, or a specimen derived therefrom. The “non-therapeutic” is a concept that does not include a medical action, that is, a treatment action on the human body by treatment.
前記式(1)〜(4)のいずれかで表される化合物を有効成分とする過活動膀胱又は頻尿の予防・改善剤、及びATP放出抑制剤は、上記使用の具体的態様の1つであり、治療的用途(医療用途)、非治療用途(非医療用途)のいずれにも適用することができる。具体的には、医薬品、医薬部外品等としての使用することができる他、各種の飲食品、飼料、ペットフード等に有効成分としてこれらの剤を配合することもできる。
本発明の予防・改善剤及びATP放出抑制剤は、液状、固形状、乳液状、ペースト状、ゲル状、パウダー状(粉末状)、顆粒状、ペレット状、スティック状等、ヒトや動物に適用されうる各種剤型をとることができる。
また、本発明の予防・改善剤及びATP放出抑制剤は、有効成分である前記式(1)〜(4)のいずれかで表される化合物のみからなるものであってもよいし、効果に影響を与えない範囲で他の成分を含有するものであってもよい。
The preventive / ameliorating agent for overactive bladder or pollakiuria and the ATP release inhibitor containing the compound represented by any one of the formulas (1) to (4) as an active ingredient are one of the specific embodiments of the above use. It can be applied to both therapeutic uses (medical uses) and non-therapeutic uses (non-medical uses). Specifically, these agents can be used as active ingredients in various foods, feeds, pet foods and the like in addition to being usable as pharmaceuticals, quasi drugs and the like.
The preventive / ameliorating agent and ATP release inhibitor of the present invention are applied to humans and animals in liquid, solid, emulsion, paste, gel, powder (powder), granule, pellet, stick, etc. Various dosage forms can be taken.
In addition, the preventive / ameliorating agent and ATP release inhibitor of the present invention may be composed only of the compound represented by any one of the above formulas (1) to (4), which is an active ingredient, and is effective. Other components may be contained within a range that does not affect.
本発明の予防・改善剤及びATP放出抑制剤を医薬品、医薬部外品に適用する場合、前記式(1)〜(4)の化合物を有効量含有させ、必要により添加剤を配合して各種剤形に調製することができる。例えば、錠剤、被覆錠剤、カプセル剤、顆粒剤、散剤、シロップ剤、腸溶剤、トローチ剤、ドリンク剤等の経口医薬として、又は、注射剤、坐剤、経皮吸収剤、外用剤等といった非経口医薬として調製することができる。これらの形態のうち、好ましい形態は経口医薬である。
種々の剤型に調製するには、添加剤を用いて常法に従って製造すればよい。添加剤は、通常用いられているものを使用することができる。添加剤の例としては、薬学的に許容される賦形剤(ソルビトール、グルコース、乳糖、デキストリン、澱粉等の糖類、炭酸カルシウム等の無機物、結晶セルロース、蒸留水、ゴマ油、とうもろこし油、オリーブ油、菜種油等)、液体担体(蒸留水、生理食塩水、ブドウ糖水溶液、エタノール等のアルコール、プロピレングリコール、ポリエチレングリコール等)、油性担体(各種の動植物油、白色ワセリン、パラフィン、ロウ類等)、安定化剤、湿潤剤、乳化剤、結合剤、等張化剤、崩壊剤、滑沢剤、増量剤、界面活性剤、分散剤、懸濁剤、希釈剤、浸透圧調整剤、pH調整剤、防腐剤、抗酸化剤、着色剤、紫外線吸収剤、保湿剤、増粘剤、光沢剤、緩衝剤、保存剤、嬌味剤、香料、被膜剤、矯臭剤、細菌抑制剤等が挙げられる。
When the preventive / ameliorating agent and ATP release inhibitor of the present invention are applied to pharmaceuticals and quasi-drugs, an effective amount of the compounds of the above formulas (1) to (4) is contained, and if necessary, various additives are added. It can be prepared into a dosage form. For example, as an oral medicine such as tablets, coated tablets, capsules, granules, powders, syrups, enteric solvents, troches, drinks, etc., or non-injectables such as injections, suppositories, transdermal absorption agents, external preparations, etc. It can be prepared as an oral medicine. Of these forms, the preferred form is oral medicine.
What is necessary is just to manufacture in accordance with a conventional method using an additive, in preparing in various dosage forms. As the additive, a commonly used additive can be used. Examples of additives include pharmaceutically acceptable excipients (sugars such as sorbitol, glucose, lactose, dextrin, starch, inorganic substances such as calcium carbonate, crystalline cellulose, distilled water, sesame oil, corn oil, olive oil, rapeseed oil. Etc.), liquid carrier (distilled water, physiological saline, aqueous glucose solution, alcohol such as ethanol, propylene glycol, polyethylene glycol, etc.), oily carrier (various animal and vegetable oils, white petrolatum, paraffin, waxes, etc.), stabilizer , Wetting agents, emulsifiers, binders, tonicity agents, disintegrating agents, lubricants, extenders, surfactants, dispersants, suspension agents, diluents, osmotic pressure adjusting agents, pH adjusting agents, preservatives, Antioxidants, colorants, ultraviolet absorbers, humectants, thickeners, brighteners, buffers, preservatives, flavoring agents, fragrances, coating agents, flavoring agents, bacteria inhibitors, and the like.
本発明の予防・改善剤、ATP放出抑制剤を飲食品、飼料、ペットフード等に適用する場合、食用又は飲料用に適した形態、例えば、顆粒状、粒状、錠剤、カプセル、ペーストなどに成形して提供することができる。さらに、前記飲食品は、一般飲食品の他、過活動膀胱、頻尿、尿意切迫感、又は切迫性尿失禁の予防又は改善をコンセプトとし、必要に応じてその旨を表示した美容食品、病者用食品、栄養機能食品又は特定保健用食品等の機能性飲食品の形態とすることができる。
飲食品の例としては、パン、麺類等に代表される小麦粉加工食品、お粥、炊き込みご飯等の米加工食品、ビスケット、ケーキ、ゼリー、チョコレート、せんべい、アイスクリーム等の菓子類、豆腐、その加工食品等の大豆加工食品、清涼飲料、果汁飲料、乳飲料、炭酸飲料等の飲料類、ヨーグルト、チーズ、バター、牛乳等の乳製品、醤油、ソース、味噌、マヨネーズ、ドレッシング等の調味料、ハム、ベーコン、ソーセージ等の蓄肉、蓄肉加工食品、はんぺん、ちくわ、魚の缶詰等の水産加工食品、調理油ならびにフライ用油等が挙げられる。また、錠剤(タブレット)、カプセル等の錠剤食、濃厚流動食、自然流動食、半消化態栄養食、成分栄養食、ドリンク栄養食等の経口経腸栄養食品、機能性食品等の形態としてもよい。
飼料としては、ウサギ、ラット、マウス等に用いる小動物用飼料、犬、猫、小鳥、リス等に用いるペットフード等が挙げられる。
When the preventive / improving agent and ATP release inhibitor of the present invention are applied to foods, drinks, feeds, pet foods, etc., it is formed into a form suitable for food or beverage, such as granules, granules, tablets, capsules, pastes, etc. Can be provided. In addition to general food and drink, the food and drink has a concept of preventing or improving overactive bladder, frequent urination, urgency, or urge urinary incontinence. It can be set as the form of functional food / beverage products, such as food for a person, functional food for nutrition, or food for specified health.
Examples of foods and beverages include processed foods such as bread and noodles, processed rice foods such as rice cakes and cooked rice, biscuits, cakes, jellies, chocolate, rice crackers, ice cream and other confectionery, tofu, Processed soy processed foods, soft drinks, fruit juice drinks, milk drinks, carbonated drinks and other dairy products, yogurt, cheese, butter, milk and other dairy products, soy sauce, sauces, miso, mayonnaise, dressings and other seasonings, Examples include meat storage such as ham, bacon and sausage, processed meat stored food, processed fish food such as hampen, chikuwa, and canned fish, cooking oil, and frying oil. In addition, tablets, tablets, and other tablet foods, concentrated liquid foods, natural liquid foods, semi-digested nutritional foods, ingredient nutritional foods, drink nutritional foods, etc. Good.
Examples of the feed include small animal feed used for rabbits, rats, mice and the like, pet food used for dogs, cats, small birds, squirrels, and the like.
これらの飲食品は、本発明の予防・改善剤又はATP放出抑制剤を含有し、これに食品原料、例えば、甘味剤、着色剤、抗酸化剤、ビタミン類、香料、ミネラル等の添加剤、タンパク質、脂質、糖質、炭水化物、食物繊維等を適宜組み合わせて、常法に従って調製することができる。 These foods and drinks contain the preventive / improving agent or ATP release inhibitor of the present invention, and food ingredients such as sweeteners, colorants, antioxidants, vitamins, fragrances, minerals and the like, Proteins, lipids, carbohydrates, carbohydrates, dietary fiber and the like can be appropriately combined and prepared according to a conventional method.
本発明の予防・改善剤及びATP放出抑制剤における前記有効成分の配合量は、その使用形態により異なるが、医薬品、例えば、錠剤、被覆錠剤、顆粒剤、散剤、カプセル剤等の経口用固形製剤、内服液剤、シロップ剤等の経口用液体製剤の場合は、固形分濃度として0.001質量%以上が好ましく、0.003質量%以上がより好ましく、0.01質量%以上がさらに好ましく、90質量%以下が好ましく、50質量%がより好ましい。あるいは、0.001〜90質量%が好ましく、0.003〜90質量がより好ましく、0.01〜90質量がさらに好ましく、0.01〜50質量%がよりさらに好ましい。飲食品やペットフード等に配合する場合は、固形分濃度として0.001質量%以上が好ましく、0.003質量%以上がより好ましく、0.01質量%以上がさらに好ましく、50質量%以下が好ましく、10質量%以下がより好ましい。あるいは、0.001〜50質量%が好ましく、0.003〜50質量がより好ましく、0.01〜50質量がさらに好ましく、0.01〜10質量%がよりさらに好ましい。 The compounding amount of the active ingredient in the preventive / ameliorating agent and ATP release inhibitor of the present invention varies depending on the form of use, but oral preparations such as pharmaceuticals such as tablets, coated tablets, granules, powders, capsules, etc. In the case of oral liquid preparations such as oral liquids and syrups, the solid content concentration is preferably 0.001% by mass or more, more preferably 0.003% by mass or more, further preferably 0.01% by mass or more, 90 The mass% or less is preferable, and 50 mass% is more preferable. Or 0.001-90 mass% is preferable, 0.003-90 mass is more preferable, 0.01-90 mass is more preferable, 0.01-50 mass% is still more preferable. When blended in food and drink, pet food, etc., the solid content concentration is preferably 0.001% by mass or more, more preferably 0.003% by mass or more, further preferably 0.01% by mass or more, and 50% by mass or less. Preferably, 10 mass% or less is more preferable. Or 0.001-50 mass% is preferable, 0.003-50 mass is more preferable, 0.01-50 mass is more preferable, 0.01-10 mass% is still more preferable.
本発明の予防・改善剤及びATP放出抑制剤の投与又は摂取量は、個体の状態、体重、性別、年齢又はその他の要因に従って適宜選択、決定できる。例えば、成人(60kg)の1日の投与又は摂取量としては、前記有効成分の乾燥物換算として、0.001mg以上が好ましく、1mg以上がより好ましく、100mg以上がさらに好ましく、80000mg以下が好ましく、40000mg以下がより好ましく、15000mg以下がさらに好ましい。あるいは、0.001〜80000mgが好ましく、1〜40000mgがより好ましく、100〜15000mgがさらに好ましい。また、本発明の予防・改善剤及びATP放出抑制剤は、1日1回〜数回に分け、又は任意の期間及び間隔で摂取・投与され得る。 Administration or intake of the preventive / ameliorating agent and ATP release inhibitor of the present invention can be appropriately selected and determined according to the individual's condition, weight, sex, age or other factors. For example, the daily administration or intake of an adult (60 kg) is preferably 0.001 mg or more, more preferably 1 mg or more, still more preferably 100 mg or more, and preferably 80,000 mg or less, in terms of dry matter of the active ingredient. 40000 mg or less is more preferable, and 15000 mg or less is more preferable. Or 0.001-80000 mg is preferable, 1-40000 mg is more preferable, and 100-15000 mg is further more preferable. Moreover, the preventive / ameliorating agent and ATP release inhibitor of the present invention can be taken or administered once a day to several times a day, or at an arbitrary period and interval.
上記医薬品、医薬部外品又は食品の摂取又は投与対象として特に限定されないが、過活動膀胱、及びその主な症状である頻尿、尿意切迫感、切迫性尿失禁等の予防、改善、治療を目的とするヒトやヒト以外の哺乳動物が好ましい。なお、摂取又は投与対象には、過活動膀胱の症状が認められるヒトやヒト以外の哺乳動物、及びそのおそれがあるヒトやヒト以外の哺乳動物、その疾患・症状の予防を期待するヒトやヒト以外の哺乳動物も含まれる。 Although it is not particularly limited as a subject of ingestion or administration of the above pharmaceuticals, quasi drugs or foods, prevention, improvement, treatment of overactive bladder and its main symptoms such as frequent urination, urgency, urge incontinence The target human or non-human mammal is preferred. In addition, the subject of ingestion or administration includes humans and non-human mammals with overactive bladder symptoms, humans and non-human mammals who may be at risk, and humans and humans who are expected to prevent the disease / symptoms. Other mammals are also included.
上述した実施形態に関し、本発明はさらに以下の予防又は改善剤、ATP放出抑制剤、製造方法、方法及び使用を開示する。 The present invention further discloses the following preventive or ameliorating agent, ATP release inhibitor, production method, method and use regarding the above-described embodiment.
<1>前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物を有効成分とする、過活動膀胱の予防又は改善剤。 <1> A prophylactic or ameliorating agent for overactive bladder, comprising as an active ingredient at least one compound selected from the group consisting of compounds represented by formulas (1) to (4).
<2>前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物を有効成分とする、頻尿の予防又は改善剤。
<3>前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物を有効成分とする、尿意切迫感の予防又は改善剤。
<4>前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物を有効成分とする、切迫性尿失禁の予防又は改善剤。
<2> A preventive or ameliorating agent for pollakiuria comprising, as an active ingredient, at least one compound selected from the group consisting of compounds represented by formulas (1) to (4).
<3> A preventive or ameliorating agent for urgency, comprising at least one compound selected from the group consisting of the compounds represented by formulas (1) to (4) as an active ingredient.
<4> A preventive or ameliorating agent for urge urinary incontinence comprising, as an active ingredient, at least one compound selected from the group consisting of compounds represented by formulas (1) to (4).
<5>過活動膀胱、頻尿、尿意切迫感、又は切迫性尿失禁の予防又は改善がATP放出抑制によるものである、<1>〜<4>のいずれか1項記載の予防又は改善剤。
<6>前記有効成分の含有量が固形分換算で0.001質量%以上であり、0.003質量%以上が好ましく、0.01質量%以上がより好ましく、90質量%以下であり、50質量%以下が好ましく、10質量%以下がより好ましい、<1>〜<5>のいずれか1項記載の予防又は改善剤。
<5> The preventive or ameliorating agent according to any one of <1> to <4>, wherein prevention or improvement of overactive bladder, frequent urination, urgency, or urge urinary incontinence is due to suppression of ATP release. .
<6> The content of the active ingredient is 0.001% by mass or more in terms of solid content, preferably 0.003% by mass or more, more preferably 0.01% by mass or more, and 90% by mass or less, 50 The preventive or ameliorating agent according to any one of <1> to <5>, preferably not more than mass%, more preferably not more than 10 mass%.
<7>前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物を有効成分とする、ATP放出抑制剤。 <7> An ATP release inhibitor comprising as an active ingredient at least one compound selected from the group consisting of compounds represented by formulas (1) to (4).
<8>前記有効成分の含有量が固形分換算で0.001質量%以上であり、0.003質量%以上が好ましく、0.01質量%以上がより好ましく、90質量%以下であり、50質量%以下が好ましく、10質量%以下がより好ましい、<7>項記載のATP放出抑制剤。 <8> The content of the active ingredient is 0.001% by mass or more in terms of solid content, preferably 0.003% by mass or more, more preferably 0.01% by mass or more, and 90% by mass or less. The ATP release inhibitor according to <7>, preferably not more than mass% and more preferably not more than 10 mass%.
<9> 前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物を、過活動膀胱、頻尿、尿意切迫感、又は切迫性尿失禁の予防又は改善剤として使用する方法。
<10> 過活動膀胱、頻尿、尿意切迫感、又は切迫性尿失禁の予防又は改善剤としての、前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物の使用。
<11> 過活動膀胱、頻尿、尿意切迫感、又は切迫性尿失禁の予防又は改善のための、前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物の非医薬的(非治療的)な使用。
<12> 過活動膀胱、頻尿、尿意切迫感、又は切迫性尿失禁の予防又は改善剤の製造のための、前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物の使用。
<13> 過活動膀胱、頻尿、尿意切迫感、又は切迫性尿失禁の予防又は改善のために用いる、前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物。
<14> 前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物を投与することを含む、過活動膀胱、頻尿、尿意切迫感、又は切迫性尿失禁の予防又は改善方法。
<9> Prevention or improvement of at least one compound selected from the group consisting of the compounds represented by formulas (1) to (4) for overactive bladder, frequent urination, urgency, or urge urinary incontinence Method to use as an agent.
<10> At least one selected from the group consisting of compounds represented by the above formulas (1) to (4) as a preventive or ameliorating agent for overactive bladder, frequent urination, urgency, or urge urinary incontinence Use of the compound.
<11> At least one selected from the group consisting of compounds represented by the above formulas (1) to (4) for preventing or improving overactive bladder, frequent urination, urgency, or urge urinary incontinence Non-pharmaceutical (non-therapeutic) use of a compound of
<12> Selected from the group consisting of compounds represented by the formulas (1) to (4) for the production of an agent for preventing or improving overactive bladder, frequent urination, urgency, or urge urinary incontinence Use of at least one compound.
<13> At least one selected from the group consisting of the compounds represented by the formulas (1) to (4) used for the prevention or improvement of overactive bladder, frequent urination, urgency, or urge urinary incontinence Species compound.
<14> Overactive bladder, frequent urination, urgency, or urge urine, comprising administering at least one compound selected from the group consisting of compounds represented by formulas (1) to (4). How to prevent or improve incontinence.
<15>ATPの放出を抑制することで過活動膀胱、頻尿、尿意切迫感、又は切迫性尿失禁を予防又は改善する、<9>〜<14>項のいずれか記載の化合物、使用又は方法。
<16>前記予防又は改善剤中の、前記有効成分の含有量が固形分換算で0.001質量%以上であり、0.003質量%以上が好ましく、0.01質量%以上がより好ましく、90質量%以下であり、50質量%以下が好ましく、10質量%以下がより好ましい、<9>〜<15>項のいずれか記載の化合物、使用又は方法。
<17>前記化合物を食品又は飲料の形態で適用する、<9>〜<16>項のいずれか記載の化合物、使用又は方法。
<15> The compound according to any one of <9> to <14>, which prevents or ameliorates overactive bladder, frequent urination, urgency, or urge urinary incontinence by suppressing the release of ATP, use or Method.
<16> The content of the active ingredient in the preventive or improving agent is 0.001% by mass or more in terms of solid content, preferably 0.003% by mass or more, more preferably 0.01% by mass or more, The compound, use or method according to any one of <9> to <15>, which is 90% by mass or less, preferably 50% by mass or less, and more preferably 10% by mass or less.
<17> The compound, use or method according to any one of <9> to <16>, wherein the compound is applied in the form of food or beverage.
<18> 前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物を、ATP放出抑制剤として使用する方法。
<19> ATP放出抑制剤としての、前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物の使用。
<20> ATP放出の抑制のための、前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物の非医薬的(非治療的)な使用。
<21> ATP放出抑制剤の製造のための、前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物の使用。
<22> ATP放出抑制のために用いる、前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物。
<23> 前記式(1)〜(4)で表される化合物からなる群より選ばれる少なくとも1種の化合物を投与することを含む、ATP放出の抑制方法。
<18> A method of using at least one compound selected from the group consisting of compounds represented by formulas (1) to (4) as an ATP release inhibitor.
<19> Use of at least one compound selected from the group consisting of compounds represented by formulas (1) to (4) as an ATP release inhibitor.
<20> Non-pharmaceutical (non-therapeutic) use of at least one compound selected from the group consisting of compounds represented by the formulas (1) to (4) for suppressing ATP release.
<21> Use of at least one compound selected from the group consisting of compounds represented by formulas (1) to (4) for the production of an ATP release inhibitor.
<22> At least one compound selected from the group consisting of compounds represented by the formulas (1) to (4) used for suppressing ATP release.
<23> A method for suppressing ATP release, comprising administering at least one compound selected from the group consisting of compounds represented by formulas (1) to (4).
<24>前記ATP放出抑制剤中の、前記有効成分の含有量が固形分換算で0.001質量%以上であり、0.003質量%以上が好ましく、0.01質量%以上がより好ましく、90質量%以下であり、50質量%以下が好ましく、10質量%以下がより好ましい、<18>〜<23>項のいずれか記載の化合物、使用又は方法。
<25>前記化合物を食品又は飲料の形態で適用する、<18>〜<24>項のいずれか記載の化合物、使用又は方法。
<24> The content of the active ingredient in the ATP release inhibitor is 0.001% by mass or more, preferably 0.003% by mass or more, more preferably 0.01% by mass or more, in terms of solid content. The compound, use or method according to any one of <18> to <23>, which is 90% by mass or less, preferably 50% by mass or less, and more preferably 10% by mass or less.
<25> The compound, use or method according to any one of <18> to <24>, wherein the compound is applied in the form of food or beverage.
以下、本発明を実施例に基づきさらに詳細に説明するが、本発明はこれに限定されるものではない。 EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example, this invention is not limited to this.
調製例1 式(1)で表される化合物
リナロール(和光純薬工業より入手、純度98%(DL体))を99.5%エタノールに濃度3%(w/v)になるように溶解し、用いた。
Preparation Example 1 Compound represented by formula (1) Linalool (obtained from Wako Pure Chemical Industries, Ltd., purity 98% (DL form)) was dissolved in 99.5% ethanol to a concentration of 3% (w / v). ,Using.
調製例2 式(2)で表される化合物
リナロールオキシド(東京化成工業より入手、純度98%)を99.5%エタノールに濃度3%(w/v)になるように溶解し、用いた。
Preparation Example 2 A compound represented by the formula (2) was used by dissolving linalool oxide (obtained from Tokyo Chemical Industry, purity 98%) in 99.5% ethanol to a concentration of 3% (w / v).
調製例3 式(3)で表される化合物
ミルセン(SIGMA-ALDRICHより入手、純度95%)を99.5%エタノールに濃度3%(w/v)になるように溶解し、用いた。
Preparation Example 3 Compound represented by formula (3) Myrcene (obtained from SIGMA-ALDRICH, purity 95%) was dissolved in 99.5% ethanol to a concentration of 3% (w / v) and used.
調製例4 式(4)で表される化合物
ボルネオール(SIGMA-ALDRICHより入手、純度97%)を99.5%エタノールに濃度3%(w/v)になるように溶解し、用いた。
Preparation Example 4 A compound represented by the formula (4) Borneol (obtained from SIGMA-ALDRICH, purity 97%) was dissolved in 99.5% ethanol to a concentration of 3% (w / v) and used.
実施例1 ATP放出抑制試験
[膀胱上皮細胞]
ヒト膀胱上皮癌細胞であるHT−1376(ATCC社より入手)を使用した。細胞情報を表1に示す。
Example 1 ATP release inhibition test [bladder epithelial cells]
HT-1376 (obtained from ATCC), which is a human bladder epithelial cancer cell, was used. Cell information is shown in Table 1.
[培地]
Earle’s(Invitrogen社製)に、10%FCS(ウシ胎仔血清)、ピルビン酸ナトリウム(0.055g/500mL)、L−グルタミン(0.146g/500mL)を添加したものを使用した。
[Culture medium]
What added 10% FCS (fetal calf serum), sodium pyruvate (0.055 g / 500 mL), and L-glutamine (0.146 g / 500 mL) to Earle's (made by Invitrogen) was used.
1.低浸透圧刺激によるATP放出
96wellプレートに、4.0×104cells/wellとなるようにHT−1376を播種し、上記培地で37℃、5%CO2条件下で、24時間培養した。培地を吸引除去して、等浸透圧液(組成を表2に示す)で細胞を2回洗浄した。調製例1〜4で調製した各化合物を下記表3に示す濃度となるよう添加した等浸透圧液を、75μL/well加えて、37℃、5%CO2環境下で60分インキュベートした。その後、調製例1〜4で調製した各化合物を下記表3に示す濃度となるよう添加した低浸透圧液(組成を表2に示す)を75μL/well添加し、37℃、5%CO2環境下で60分インキュベートした。低浸透圧刺激により培地中に放出されたATP量を測定するため、細胞培養液50μLをサンプルとして回収した。
また、等浸透圧液及び低浸透圧液に式(1)〜(4)の化合物を添加しない以外は上記と同様にして細胞培養を行い、回収した培養液をコントロールサンプルとした。
1. ATP release by low osmotic pressure stimulation HT-1376 was seeded on a 96-well plate at 4.0 × 10 4 cells / well, and cultured in the above medium under conditions of 37 ° C. and 5% CO 2 for 24 hours. The medium was removed by suction, and the cells were washed twice with an isotonic solution (composition is shown in Table 2). 75 μL / well of an isosmotic solution to which the respective compounds prepared in Preparation Examples 1 to 4 were added so as to have the concentrations shown in Table 3 below was added and incubated at 37 ° C. in a 5% CO 2 environment for 60 minutes. Thereafter, 75 μL / well of a low osmotic pressure solution (the composition is shown in Table 2) to which each compound prepared in Preparation Examples 1 to 4 was added to a concentration shown in Table 3 below, was added at 37 ° C., 5% CO 2. Incubated for 60 minutes under environment. In order to measure the amount of ATP released into the medium by hypoosmotic stimulation, 50 μL of cell culture solution was collected as a sample.
In addition, cell culture was performed in the same manner as above except that the compounds of formulas (1) to (4) were not added to the isotonic solution and the low osmotic solution, and the collected culture solution was used as a control sample.
2.ATP放出量の測定
回収したサンプル溶液中のATP濃度を、ATP Bioluminescent Assay Kit(SIGMA社製)を用いてルシフェリン・ルシフェラーゼ法により測定した。サンプル溶液と、ATP Bioluminescent Assay Kit中のTP Assay Mix solutionとを等量で混合し、撹拌後にホタルルシフェラーゼ活性を1秒間測定してATP量を測定した。同様に、コントロールサンプル中のATP量を測定した。
ルシフェリン・ルシフェラーゼ法によるATP濃度の測定では、サンプル溶液中に含まれている式(1)〜(4)のいずれかの化合物にクエンチング効果がある場合、ATP濃度が低く計算されてしまう。そこで、下記式(A)により、測定したサンプル中のATP量をATP添加回収率で補正した値を、ATP放出率とした。なお、ATP添加回収率とは、既知ATP量を含有する溶媒に式(1)〜(4)の化合物を添加した場合の、該溶媒中における既知ATP量の測定可能割合をいい、式(A)におけるATP添加回収率は、溶媒対照(化合物添加なし)のATP量に対する相対値とした。結果を表3に示す。
式(A)
ATP放出率=式(1)〜(4)のいずれかの化合物を添加したサンプル中のATP量/{(ATP添加回収率)×(コントロールサンプル中のATP量)}
2. Measurement of ATP release amount The ATP concentration in the collected sample solution was measured by luciferin-luciferase method using ATP Bioluminescent Assay Kit (manufactured by SIGMA). The sample solution and the TP Assay Mix solution in the ATP Bioluminescent Assay Kit were mixed in equal amounts, and after stirring, the firefly luciferase activity was measured for 1 second to determine the amount of ATP. Similarly, the amount of ATP in the control sample was measured.
In the measurement of ATP concentration by the luciferin-luciferase method, if any of the compounds of formulas (1) to (4) contained in the sample solution has a quenching effect, the ATP concentration is calculated to be low. Therefore, a value obtained by correcting the amount of ATP in the measured sample by the following formula (A) with the ATP addition recovery rate was defined as the ATP release rate. The ATP addition recovery rate means the measurable proportion of the known ATP amount in the solvent when the compounds of formulas (1) to (4) are added to the solvent containing the known ATP amount. The ATP addition recovery rate in () was a relative value to the ATP amount of the solvent control (no compound addition). The results are shown in Table 3.
Formula (A)
ATP release rate = ATP amount in the sample to which any compound of formulas (1) to (4) was added / {(ATP addition recovery rate) × (ATP amount in the control sample)}
参考例1
式(1)〜(4)の化合物にかえて、下記構造式で表されるリモネンを用いた以外は、実施例1と同様にしてATP放出抑制試験を行った。
Reference example 1
An ATP release inhibition test was conducted in the same manner as in Example 1 except that limonene represented by the following structural formula was used instead of the compounds of formulas (1) to (4).
なお、リモネンは、リモネン(和光純薬工業より入手、純度95%以上)を99.5%エタノールに濃度3%(w/v)になるように溶解し、用いた。
結果を表3に示す。
Limonene (Limonene (obtained from Wako Pure Chemical Industries, purity 95% or more)) was dissolved in 99.5% ethanol to a concentration of 3% (w / v) and used.
The results are shown in Table 3.
表3に示すように、前記式(1)〜(4)のいずれかの化合物を添加したサンプルのATP放出率は、コントロールと比較して有意な差が見られた。すなわち、等浸透圧から低浸透圧へと浸透圧を変化させて膀胱上皮細胞を伸展させると、前記式(1)〜(4)の化合物を添加しないコントロールサンプルではATPの放出が亢進するのに対し、前記式(1)〜(4)のいずれかの化合物を添加したサンプルでは、このATP放出が抑制された。また、参考用化合物リモネンを添加したサンプルでは、濃度0.003%でも、コントロールと比較してATP放出率に有意な差は見られなかった。
これらの結果から、前記式(1)〜(4)の化合物は、膀胱上皮細胞の伸展時に亢進するATP放出を抑制する作用を有することが確認された。
As shown in Table 3, a significant difference was observed in the ATP release rate of the sample to which any of the compounds of formulas (1) to (4) was added as compared with the control. That is, when the bladder epithelial cells are expanded by changing the osmotic pressure from isotonic pressure to low osmotic pressure, ATP release is enhanced in the control sample to which the compounds of the formulas (1) to (4) are not added. On the other hand, this ATP release was suppressed in the sample to which any of the compounds of formulas (1) to (4) was added. In the sample to which the reference compound limonene was added, no significant difference was observed in the ATP release rate compared to the control even at a concentration of 0.003%.
From these results, it was confirmed that the compounds of the above formulas (1) to (4) have an action of suppressing ATP release that is enhanced during the extension of bladder epithelial cells.
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JP2019214618A (en) * | 2019-09-12 | 2019-12-19 | 花王株式会社 | Uroplakin expression promoter |
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000095681A (en) * | 1998-09-18 | 2000-04-04 | Hidonisuto Biochemical Technol Co Ltd | Topical application pharmaceutical composition for healing wound |
WO2009037861A1 (en) * | 2007-09-20 | 2009-03-26 | Kao Corporation | Β-glucuronidase inhibitor |
JP2009139371A (en) * | 2007-11-15 | 2009-06-25 | Anbas:Kk | Evaluation method of blood circulation accelerating activity, blood circulation accelerating substance screening method and blood circulation accelerating agent |
JP2012077033A (en) * | 2010-10-01 | 2012-04-19 | Kinki Univ | Helicobacter pylori motility inhibitor |
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WO2009037861A1 (en) * | 2007-09-20 | 2009-03-26 | Kao Corporation | Β-glucuronidase inhibitor |
JP2009139371A (en) * | 2007-11-15 | 2009-06-25 | Anbas:Kk | Evaluation method of blood circulation accelerating activity, blood circulation accelerating substance screening method and blood circulation accelerating agent |
JP2012077033A (en) * | 2010-10-01 | 2012-04-19 | Kinki Univ | Helicobacter pylori motility inhibitor |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110913839A (en) * | 2017-05-22 | 2020-03-24 | Gbs全球生物制药公司 | Myrcene and cannabinoid containing compositions targeted to TRPV1 |
JP2020520966A (en) * | 2017-05-22 | 2020-07-16 | ジービーエス グローバル バイオファーマ,インコーポレイテッド | Myrcene- and cannabinoid-containing compositions targeting TRPV1 |
US11944593B2 (en) | 2017-05-22 | 2024-04-02 | Gbs Global Biopharma, Inc. | Myrcene-containing complex mixtures targeting TRPV1 |
JP2019214618A (en) * | 2019-09-12 | 2019-12-19 | 花王株式会社 | Uroplakin expression promoter |
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