JP3377997B2 - Substance P antagonist - Google Patents
Substance P antagonistInfo
- Publication number
- JP3377997B2 JP3377997B2 JP2002102406A JP2002102406A JP3377997B2 JP 3377997 B2 JP3377997 B2 JP 3377997B2 JP 2002102406 A JP2002102406 A JP 2002102406A JP 2002102406 A JP2002102406 A JP 2002102406A JP 3377997 B2 JP3377997 B2 JP 3377997B2
- Authority
- JP
- Japan
- Prior art keywords
- extract
- substance
- fraction
- antagonist
- antagonism
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- Medicines Containing Plant Substances (AREA)
Description
【発明の詳細な説明】
【０００１】
【産業上の利用分野】本発明は、サブスタンスＰ拮抗剤
に関する。
【０００２】
【従来の技術】紅景天は、チベット等の高山地帯に生育
する多年生草本植物、べんけいそう科のＲｈｏｄｉｏｌ
ａ ｒｏｓｅａ Ｌ属植物の根および根茎で、中国では
民間薬として、抗疲労、抗無酸素症、抗毒、貧血改善の
目的で使用されている。また中国では、スポーツ選手の
酸欠、疲労回復の目的で、紅景天エキスを含有した健康
飲料が市販されている。しかしながら、紅景天およびそ
の抽出エキスがサブスタンスＰ拮抗作用による喘息、ア
レルギー、炎症、疼痛等の改善に有効であることは知ら
れていない。
【０００３】サブスタンスＰは、痛みあるいは炎症性情
報の神経伝達物質と考えられている。サブスタンスＰ拮
抗とは、サブスタンスＰがその受容体と結合することを
拮抗阻害することをいうが、未だこの機序で効く治療薬
は、市場には存在していない。
【０００４】
【発明が解決しようとする課題】本発明の目的は、サブ
スタンスＰ拮抗作用による喘息、アレルギー、炎症、疼
痛等の改善に有効である薬剤を提供することにある。
【０００５】
【課題を解決するための手段】本発明者は、上記課題を
解決するために鋭意検討を行った結果、サブスタンスＰ
拮抗作用による喘息、アレルギー、炎症、疼痛等の改善
に有効であることを見い出し、本発明を完成するに至っ
た。
【０００６】本発明は、紅景天またはその抽出エキスを
有効成分として含有することを特徴とするサブスタンス
Ｐ拮抗剤に関する。
【０００７】以下、本発明について詳しく説明する。本
発明の紅景天とは、べんけいそう科のＲｈｏｄｉｏｌａ
ｒｏｓｅａ Ｌ属植物の根および根茎を乾燥させたも
のをいう。また、紅景天抽出エキスとは、紅景天を、メ
タノールやエタノールなどのアルコール類や水等の抽出
溶媒によって抽出されたエキスである。
【０００８】抽出方法、抽出条件は、任意に選択、設定
することができる。次に、得られた抽出エキスを植物成
分の精製、単離に用いられる慣用手段、たとえば各種溶
媒間の分配クロマトグラフィー等によって分画する。分
配クロマトグラフィー処理に用いられる各種溶媒として
は、水、またはアルコール類（メタノール、エタノー
ル、ブタノール等）、エステル類（酢酸エチル、酢酸ブ
チル等）、エーテル類（エチルエーテル、ジオキサン
等）、炭化水素（ベンゼン、トルエン、ヘキサン等）、
ハロゲン化炭化水素（クロロホルム、塩化エチレン等）
またはこれらの混合溶媒を用いればよい。
【０００９】
【実施例】以下に、紅景天抽出エキスの抽出例、抽出エ
キス分画例、薬理試験例を示すが、本発明はこれに限定
されるものではない。
【００１０】（紅景天エキスの抽出例）紅景天２２０ｇ
を室温にて、メタノール１５００ｍｌで２回抽出を行っ
た後、メタノールを留去し乾燥させ、メタノール抽出物
９ｇを得た。（収率４．１％）
【００１１】（抽出エキス分画例）メタノール抽出物の
乾燥品５ｇを２５０ｍｌの蒸留水に溶かし、先ず２５０
ｍｌのジエチルエーテルで４回抽出し、これをエーテル
画分とする。次に残った水層に対して、２５０ｍｌの酢
酸エチルで４回抽出し、これを酢酸エチル画分とする。
更に同様に残った水層に対して、２５０ｍｌの水飽和ｎ
−ブタノールで４回抽出し、これをブタノール画分と
し、残った画分を水画分とする。各画分の溶媒を留去
後、凍結乾燥させて固形物を得た。それぞれの画分の固
形物の収率は、紅景天のメタノール抽出物乾燥品５ｇに
対して、エーテル画分２１重量％、酢酸エチル画分１１
重量％、ブタノール画分３１重量％、水画分３７重量％
であった。更に水画分については、限外濾過（分画分子
量１０００）を行い、高分子量側と低分子量側に分画
し、凍結乾燥させて固形物を得た。その結果、水画分の
固形物に対して、高分子量側の固形物の収率５４％、低
分子量側の固形物４６重量％が得られた。
【００１２】（サブスタンスＰ拮抗試験）マグヌス浴槽
をアトロピン、ジフェンヒドラミン、インドメタシンを
各１μｇ／ｍｌ含む３７℃の生理食塩水で満たし、その
中にモルモットの回腸をつるす。紅景天のエキスのメタ
ノール抽出品固形物および各抽出画分固形物を下記の濃
度に溶解させた状態でサブスタンスＰ（１０ｎｇ／ｍ
ｌ）が回腸に及ぼす収縮高を測定し、阻害剤のない場合
と比較することで収縮阻害率を求める。なお、アトロピ
ン、ジフェンヒドラミン、インドメタシンは、より特異
性を上げるために加えている。対照品としてサブスタン
スＰ拮抗物質であるスパンタイド１μｇ／ｍｌについ
て、同様の操作を行った。その結果を表１に示す。
【００１３】
【表１】
【００１４】以上の結果から、特に紅景天の水画分固形
物および水画分の高分子量側画分固形物、紅景天メタノ
ールエキス抽出固形物にスパンタイドほど作用は強くな
いが、サブスタンスＰ拮抗作用があることが認められ
た。
【００１５】サブスタンスＰ拮抗作用による喘息抑制効
果は、Ｆｕｊｉｉ．Ｔ等のＢｒ．Ｊ．Ｐｈａｒｍａｒｏ
ｌ．ｖｏｌ．１０７第７８５〜７８９頁（１９９２）に
記載されたとおり、モルモットを用いた喘息モデル実験
により、気道浮腫の抑制効果により確認した。
【００１６】炎症抑制効果については、Ｌｅｍｂｅｃ
ｋ，Ｆ．等のＢｒ．Ｊ．Ｐｈａｒｍａｃｏｌ．ｖｏｌ．
１０５，第５２７〜５３０頁（１９９２）に記載された
とおり、神経電気刺激およびマスタードオイル塗布によ
っておこるラット後足の炎症が制御されることにより確
認した。
【００１７】疼痛改善効果については、Ｇａｒｒｅｔ，
Ｃ．等のＰｒｏｃ．Ｎａｔｌ．Ａｃａｄ．Ｓｃｉ．Ｕ．
Ｓ．Ａ．ｖｏｌ．８８，第１０２０８〜１０２１２頁
（１９９１）に記載されたとおり、マウスを用いたホル
マリン疼痛試験、フェニルベンゾキノンライジング試験
によりその鎮痛活性を確認した。
【００１８】
【効果】本発明によって、紅景天およびその抽出エキス
が、サブスタンスＰ拮抗作用を有することが明らかとな
り、紅景天およびその抽出エキスはサブスタンスＰ拮抗
作用による喘息、アレルギー、炎症、疼痛等の改善に有
効である。Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a substance P antagonist. [0002] Hongjingtian is a perennial herbaceous plant that grows in alpine areas such as Tibet, and Rhodiol, a member of the family Benicaceae.
a The root and rhizome of a rosea L genus plant. It is used as a folk medicine in China for the purpose of anti-fatigue, anti-anoxia, anti-poisoning, and improving anemia. In China, health drinks containing Hongjing Tian extract are marketed for the purpose of relieving athletes of lack of oxygen and fatigue. However, it is not known that Kungjing Tian and its extract are effective in improving asthma, allergy, inflammation, pain, etc. by substance P antagonism. [0003] Substance P is considered to be a neurotransmitter of pain or inflammatory information. Substance P antagonism refers to antagonistic inhibition of substance P binding to its receptor, but there is no therapeutic agent that works by this mechanism yet on the market. [0004] An object of the present invention is to provide a drug which is effective for ameliorating asthma, allergy, inflammation, pain, etc. by substance P antagonism. The present inventor has conducted intensive studies to solve the above-mentioned problems, and as a result, has found that the substance P
The present inventors have found that it is effective for amelioration of asthma, allergy, inflammation, pain and the like by antagonism, and have completed the present invention. [0006] The present invention relates to a substance P antagonist, which comprises as an active ingredient red vine or an extract thereof. Hereinafter, the present invention will be described in detail. The Red Kageten of the present invention is Rhodiola of the family
It refers to a dried root and rhizome of a rosea L genus plant. In addition, the red-kageten extract is an extract obtained by extracting red-kageten with an extraction solvent such as alcohols such as methanol and ethanol and water. The extraction method and extraction conditions can be arbitrarily selected and set. Next, the obtained extract is fractionated by conventional means used for purification and isolation of plant components, for example, partition chromatography between various solvents. Various solvents used for partition chromatography include water or alcohols (eg, methanol, ethanol, butanol), esters (eg, ethyl acetate, butyl acetate), ethers (eg, ethyl ether, dioxane), hydrocarbons (eg, Benzene, toluene, hexane, etc.),
Halogenated hydrocarbons (chloroform, ethylene chloride, etc.)
Alternatively, a mixed solvent thereof may be used. [0009] Examples of the extraction of the extract of Hongjingtian extract, examples of fractionation of the extract, and examples of pharmacological tests are shown below, but the present invention is not limited thereto. (Extraction example of Hongjing heaven extract) Hongjing heaven 220g
Was extracted twice with 1500 ml of methanol at room temperature, and then methanol was distilled off and dried to obtain 9 g of a methanol extract. (Yield 4.1%) (Example of Extractive Extract Fractionation) 5 g of a dried methanol extract was dissolved in 250 ml of distilled water.
Extract 4 times with ml of diethyl ether and use this as the ether fraction. Next, the remaining aqueous layer was extracted four times with 250 ml of ethyl acetate, and this was used as an ethyl acetate fraction.
Further, a water saturated n
-Extract 4 times with butanol, use this as the butanol fraction, and use the remaining fraction as the water fraction. After evaporating the solvent of each fraction, it was freeze-dried to obtain a solid. The yield of solids in each fraction was 21% by weight of the ether fraction and 11% of the ethyl acetate fraction with respect to 5 g of the dried product of the methanol extract of Hongjingtian.
Wt%, butanol fraction 31 wt%, water fraction 37 wt%
Met. Further, the water fraction was subjected to ultrafiltration (fraction molecular weight: 1,000), fractionated into a high molecular weight side and a low molecular weight side, and freeze-dried to obtain a solid. As a result, the yield of the solid matter on the high molecular weight side was 54% and the solid matter on the low molecular weight side was 46% by weight based on the solid matter in the water fraction. (Substance P Antagonism Test) A Magnus bath was filled with a physiological saline solution containing 1 μg / ml of atropine, diphenhydramine and indomethacin at 37 ° C., and the guinea pig ileum was suspended therein. The substance P (10 ng / m 2) was dissolved in the solid content of the methanol extract of the extract of Kungjing heaven and the solids of each extracted fraction at the following concentrations.
The shrinkage inhibition rate is determined by measuring the height of the contraction of l) on the ileum and comparing with the case without the inhibitor. In addition, atropine, diphenhydramine, and indomethacin were added to further increase the specificity. The same operation was performed for 1 μg / ml of a substance P antagonist spuntide as a control. Table 1 shows the results. [Table 1] [0014] From the above results, it is not particularly strong on the solid matter of the water fraction of Hongjingtian, the high-molecular-weight fraction of the water fraction, and the solid matter of the red extract of Mingjingtian methanol extract. Antagonism was observed. The asthma suppression effect by substance P antagonism is described in Fujii. Br. J. Pharmaro
l. vol. 107, pages 785 to 789 (1992), confirmed by an airway edema inhibitory effect by an asthma model experiment using guinea pigs. Regarding the effect of suppressing inflammation, Lembec
k, F. Br. J. Pharmacol. vol.
105, pp. 527-530 (1992), which was confirmed by controlling inflammation of the rat hind paw caused by electrical nerve stimulation and application of mustard oil. Regarding the effect of improving pain, see Garret,
C. Proc. Natl. Acad. Sci. U.
S. A. vol. 88, pp. 10208-10212 (1991), the analgesic activity was confirmed by a formalin pain test and a phenylbenzoquinone rising test using mice. EFFECT OF THE INVENTION According to the present invention, it is clear that Hongjingtian and its extract have a substance P antagonistic effect, and that Hongjiantian and its extract have asthma, allergy, inflammation and pain due to substance P antagonism. It is effective for improvement of etc.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ Ａ６１Ｐ 43/00 １１１ Ａ６１Ｐ 43/00 １１１ (56)参考文献 Ａｋｓｅｎｏｖａ，Ｒ．Ａ．ｅｔ ａ ｌ，Ｓｔｉｍｕｌａｔｉｎｇ ａｎｄ ａｄａｏｔｏｇｅｎｉｃ ｅｆｆｗｃｔ ｓ ｏｆ ａ ｒｅｆｉｎｅｄ ｐｒｅ ｐａｒａｔｉｏｎ ｏｆ Ｒｈｏｄｉｏ ｌａ ｒｏｓｅａ；ｒｈｏｄｏｓｏｓｉ ｎ，Ｓｔｉｍｕｌｙｔｏｒｕ Ｔｓｅｎ ｔ．Ｎｅｒｖ．Ｓｉｓｔ．，ロシア，Ｓ ａｒａｔｉｋｏｖ，Ａ．Ｓ．．，1966 年，ｐ．77−79，（Ｃｈｅｍ．Ａｂ ｓ．，ＡＮ．70：2344参照) (58)調査した分野(Int.Cl.7，ＤＢ名) A61K 35/78 ＢＩＯＳＩＳ（ＤＩＡＬＯＧ) ＣＡ（ＳＴＮ)──────────────────────────────────────────────────続 き Continued on the front page (51) Int. Cl. 7 Identification code FI A61P 43/00 111 A61P 43/00 111 (56) References Aksenova, R.A. A. et al, Stimulating and adatomogenic efwcts of a refined preparation of Rhodio la rosea; rhodososin, StimulitoluTsent. Nerv. Sist. Saratikov, A., Russia. S. . , 1966, p. 77-79, (See Chem. Abs., AN. 70: 2344) (58) Fields investigated (Int. Cl. 7 , DB name) A61K 35/78 BIOSIS (DIALOG) CA (STN)
Claims (1)
として含有することを特徴とするサブスタンスＰ拮抗
剤。(57) [Claims 1] A substance P antagonist comprising, as an active ingredient, Red Keiten or an extract thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002102406A JP3377997B2 (en) | 2002-04-04 | 2002-04-04 | Substance P antagonist |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002102406A JP3377997B2 (en) | 2002-04-04 | 2002-04-04 | Substance P antagonist |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP34841193A Division JP3320879B2 (en) | 1993-12-27 | 1993-12-27 | Anti-gastrin agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002308794A JP2002308794A (en) | 2002-10-23 |
| JP3377997B2 true JP3377997B2 (en) | 2003-02-17 |
Family
ID=19193703
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002102406A Expired - Lifetime JP3377997B2 (en) | 2002-04-04 | 2002-04-04 | Substance P antagonist |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3377997B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2021020880A (en) * | 2019-07-30 | 2021-02-18 | 株式会社東洋新薬 | Tie2 ACTIVATOR, AND AGENT FOR PREVENTING OR IMPROVING SWELLING |
-
2002
- 2002-04-04 JP JP2002102406A patent/JP3377997B2/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| Ａｋｓｅｎｏｖａ，Ｒ．Ａ．ｅｔ ａｌ，Ｓｔｉｍｕｌａｔｉｎｇ ａｎｄ ａｄａｏｔｏｇｅｎｉｃ ｅｆｆｗｃｔｓ ｏｆ ａ ｒｅｆｉｎｅｄ ｐｒｅｐａｒａｔｉｏｎ ｏｆ Ｒｈｏｄｉｏｌａ ｒｏｓｅａ；ｒｈｏｄｏｓｏｓｉｎ，Ｓｔｉｍｕｌｙｔｏｒｕ Ｔｓｅｎｔ．Ｎｅｒｖ．Ｓｉｓｔ．，ロシア，Ｓａｒａｔｉｋｏｖ，Ａ．Ｓ．．，１９６６年，ｐ．７７−７９，（Ｃｈｅｍ．Ａｂｓ．，ＡＮ．７０：２３４４参照） |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002308794A (en) | 2002-10-23 |
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