JPH049329A - Remedy for allergic disease - Google Patents
Remedy for allergic diseaseInfo
- Publication number
- JPH049329A JPH049329A JP11137090A JP11137090A JPH049329A JP H049329 A JPH049329 A JP H049329A JP 11137090 A JP11137090 A JP 11137090A JP 11137090 A JP11137090 A JP 11137090A JP H049329 A JPH049329 A JP H049329A
- Authority
- JP
- Japan
- Prior art keywords
- chinesin
- allergic diseases
- thromboxane
- allergic
- remedy
- 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.)
- Pending
Links
- 208000026935 allergic disease Diseases 0.000 title claims abstract description 25
- BQPUGGCSGFPVKS-UHFFFAOYSA-N Chinensin Natural products COc1ccc(cc1OC)c2c3OCOc3cc4cc5COC(=O)c5cc24 BQPUGGCSGFPVKS-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229930193793 chinesin Natural products 0.000 claims abstract description 22
- 239000000126 substance Substances 0.000 claims abstract description 16
- 206010020751 Hypersensitivity Diseases 0.000 claims abstract description 10
- 239000004480 active ingredient Substances 0.000 claims abstract description 9
- 230000007815 allergy Effects 0.000 claims abstract description 7
- 208000006673 asthma Diseases 0.000 claims abstract description 6
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims abstract description 6
- 206010002198 Anaphylactic reaction Diseases 0.000 claims abstract description 5
- 208000003455 anaphylaxis Diseases 0.000 claims abstract description 5
- 201000010099 disease Diseases 0.000 claims abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 5
- 230000036783 anaphylactic response Effects 0.000 claims abstract description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract 2
- 239000003814 drug Substances 0.000 claims description 25
- 229940124597 therapeutic agent Drugs 0.000 claims description 14
- 150000002617 leukotrienes Chemical class 0.000 abstract description 17
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 abstract description 13
- 230000003042 antagnostic effect Effects 0.000 abstract description 7
- 241000196324 Embryophyta Species 0.000 abstract description 3
- 240000005342 Hypericum chinense Species 0.000 abstract 1
- 239000004615 ingredient Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- QYPGFMLLGVPVHG-UHFFFAOYSA-N chinesin II Natural products CC(C)=CCC1(C)C(=O)C(C(=O)C(C)C)=C(O)C(CC2C(CCC2C(C)=C)(C)O)=C1O QYPGFMLLGVPVHG-UHFFFAOYSA-N 0.000 description 5
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical class CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
- SEHZNEFMBPPMQP-UHFFFAOYSA-N chinesin I Natural products CC(C)=CCC1(C)C(=O)C(C(=O)C(C)CC)=C(O)C(CC2C(CCC2C(C)=C)(C)O)=C1O SEHZNEFMBPPMQP-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 4
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 3
- 108010003541 Platelet Activating Factor Proteins 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000003630 histaminocyte Anatomy 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000016160 smooth muscle contraction Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 241000700199 Cavia porcellus Species 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 230000002517 constrictor effect Effects 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 210000003437 trachea Anatomy 0.000 description 2
- LMQBMWHHGVZWMR-UHFFFAOYSA-N 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-1-benzopyran-2-carboxylic acid Chemical compound C1=CC(C(C)=O)=C(O)C(CCC)=C1OCC(O)COC1=CC=C2C(=O)C=C(C(O)=O)OC2=C1CCC LMQBMWHHGVZWMR-UHFFFAOYSA-N 0.000 description 1
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 1
- 108010093579 Arachidonate 5-lipoxygenase Chemical class 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 102100026515 Cytochrome P450 2S1 Human genes 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000009438 IgE Receptors Human genes 0.000 description 1
- 108010073816 IgE Receptors Proteins 0.000 description 1
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 101100545004 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YSP2 gene Proteins 0.000 description 1
- 241000124033 Salix Species 0.000 description 1
- 208000032957 Seasonal conjunctivitis Diseases 0.000 description 1
- 108010069102 Thromboxane-A synthase Proteins 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 201000010435 allergic urticaria Diseases 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 150000002066 eicosanoids Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 1
- GWNVDXQDILPJIG-NXOLIXFESA-N leukotriene C4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-NXOLIXFESA-N 0.000 description 1
- OTZRAYGBFWZKMX-JUDRUQEKSA-N leukotriene E4 Chemical compound CCCCCC=CCC=C\C=C\C=C\[C@@H](SC[C@H](N)C(O)=O)[C@@H](O)CCCC(O)=O OTZRAYGBFWZKMX-JUDRUQEKSA-N 0.000 description 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
- 238000003808 methanol extraction Methods 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000003768 thromboxane synthase inhibitor Substances 0.000 description 1
- 150000003595 thromboxanes Chemical class 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、チャイネシン（ｃｈｉｎｓｔｉｎ）を有効成
分とするアレルギー性疾患治療剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a therapeutic agent for allergic diseases containing chinstin as an active ingredient.
［従来の技術］
アレルギー性疾患は、アレルギーにより発症する疾患を
さす。アレルギー反応は、関与する細胞や抗体の種類、
反応様式などに従ってＩ型からｖ型にまで分類される。[Prior Art] Allergic diseases refer to diseases caused by allergies. Allergic reactions depend on the types of cells and antibodies involved,
They are classified from type I to type V according to the reaction mode.
そのなかで最も発現頻度が高く、はとんどすべてのアレ
ルギー反応にかかわっているのがＩ型アレルギー反応で
ある。Among these, type I allergic reactions occur most frequently and are involved in almost all allergic reactions.
Ｉ型アレルギーにより起こる疾患には、気管支喘息、ア
レルギー性鼻炎、じん麻疹、アナフィラキシ−１季節性
結膜炎などがある。この型のアレルギーでは、生体が抗
原に感作されることによりＩｇＥ抗体が産生され、その
ＩｇＥ抗体が肥満細胞や好塩基球のＩｇＥレセプターに
結合し、これに再び侵入した抗原が働くことにより、ヒ
スタミン、ロイコトリエン、プロスタグランジン、トロ
ンボキサン、血小板活性化因子（Ｐ Ａ Ｆ）などのケ
ミカルメデイエータ−が放出され症状が発現する。Diseases caused by type I allergies include bronchial asthma, allergic rhinitis, urticaria, and anaphylaxis-1 seasonal conjunctivitis. In this type of allergy, IgE antibodies are produced when the body becomes sensitized to the antigen, and the IgE antibodies bind to IgE receptors on mast cells and basophils. Chemical mediators such as histamine, leukotrienes, prostaglandins, thromboxane, and platelet activating factor (PAF) are released and symptoms develop.
したがって、アレルギー性疾患治療剤としては、■肥満
細胞からのケミカルメデイエータ−の放出を抑制する薬
剤、■肥満細胞内でのケミカルメデイエータ−の生合成
を抑制する薬剤、■ケミカルメデイエーターが作用する
細胞のレセプター上でケミカルメデイエータ−と拮抗す
る薬剤、■ケミカルメデイエーターの作用に機能的に拮
抗する薬剤などが挙げられる。■の例として抗ヒスタミ
ン薬など、■の例としてリポキシゲナーゼ阻害薬、トロ
ンボキサンＡ２合成酵素阻害薬など、■の例としてロイ
コトリエン拮抗薬、ＰＡＦ拮抗薬、抗コリン薬など、並
びに■の例としてβ２刺激薬などが知られており、特に
■、■及び■の薬剤の多くが現在臨床試験の段階にある
（田坂賢二、化学と工業、第４２巻、第８号、第５５〜
５９頁、１９８９年９゜［発明が解決しようとする課題
］
ロイコトリエン又はトロンボキサンＡ２がヒトの気管支
喘息を含むアレルギー性疾患における重要なケミカルメ
デイエータ−であることは立証されているが、現在のと
ころこれらのメデイエータ−に対してともに有効に作用
する拮抗剤は見出されていない。アレルギーに関与する
ケミカルメデイエータ−は多数存在し、これらが複雑に
関与して１つの主症状をもつアレルギー病変として出現
するため、抗アレルギー薬としては多彩なケミカルメデ
イエータ−拮抗作用を併せもつものが理想と考えられる
。Therefore, as therapeutic agents for allergic diseases, there are: 1) drugs that suppress the release of chemical mediators from mast cells, 2) drugs that suppress the biosynthesis of chemical mediators within mast cells, and 2) drugs that act as chemical mediators. Examples include drugs that antagonize chemical mediators on cell receptors, and drugs that functionally antagonize the action of chemical mediators. Examples of ■ include antihistamines, examples of ■ include lipoxygenase inhibitors, thromboxane A2 synthase inhibitors, etc. examples of ■ include leukotriene antagonists, PAF antagonists, anticholinergic drugs, etc., and examples of ■ include β2 stimulation. Many of the drugs listed in ■, ■, and ■ are currently in the clinical trial stage (Kenji Tasaka, Chemistry and Industry, Vol. 42, No. 8, No. 55-
59, 1989 9゜[Problem to be Solved by the Invention] It has been established that leukotriene or thromboxane A2 is an important chemical mediator in human allergic diseases including bronchial asthma. However, an antagonist that effectively acts on both of these mediators has not been found. There are many chemical mediators that are involved in allergies, and these are involved in a complex manner and appear as allergic lesions with one main symptom. Therefore, anti-allergy drugs that have antagonistic effects on a variety of chemical mediators are recommended. is considered ideal.
本発明は、ロイコトリエン及びトロンボキサンＡ２拮抗
作用をともに有する植物成分チャイネシンを有効成分と
するアレルギー性疾患治療剤を提供することを目的とし
ている。An object of the present invention is to provide a therapeutic agent for allergic diseases whose active ingredient is chinesin, a plant component that has both leukotriene and thromboxane A2 antagonistic effects.
［課題を解決するための手段］
本発明者は、チャイネシン（ｃｈｉｎｅｌｉｃ）に、優
れたロイコトリエン（ＬＴｓ）拮抗作用及びトロンボキ
サンＡ２ （ＴＸＡ２ ）拮抗作用が存することを見出
し、本発明を完成させるに至った。[Means for Solving the Problems] The present inventor discovered that chinesin has excellent leukotriene (LTs) antagonistic activity and thromboxane A2 (TXA2) antagonistic activity, and was able to complete the present invention. Ta.
チャイネシンは、Ｍ、 ＮｘｇａｉとＭ、 Ｔａｄａ
ｆｃＨＥＩｓＴＲＹＬＥＴＴＥＲＳ、 ｐｐ、１３
３７−１３４０．１９８７）により、グラム陽性細菌に
対する抗菌化合物としてＨマｐｅｒｉｃｕｍｃｈｉｎｅ
ｎｓｅ Ｌ、 （Ｇｎｔｔｉｌｅｒｉｃ科；日本名：
ビュウヤナギ）の花から単離された公知の物質である。Chinesin is M, Nxgai and M, Tada
fcHEIsTRYLETTERS, pp, 13
37-1340.1987), Hpericumcine was used as an antibacterial compound against Gram-positive bacteria.
nse L, (family Gnttilericidae; Japanese name:
This is a known substance isolated from the flowers of the willow tree.
また、このチャイネシンは、抗ウイルス活性作用をもつ
ことが知られている（日本農芸化学会誌、６４（３）、
１９９０年、メ９６頁参照）。チャイネシンにはチ
ャイネシンＩとチャイネシン■があり、該植物体中では
これらの混合物として存在している。チャイネシンは下
記の構造式をもち、
１ ： Ｒ＝Ｃ２Ｈ。In addition, this chinesin is known to have antiviral activity (Journal of the Japanese Society of Agricultural Chemistry, 64(3),
1990, page 96). There are two types of chinesin, chinesin I and chinesin II, and they exist as a mixture in the plant. Chinesin has the following structural formula, 1: R=C2H.
ｎ ： Ｒ＝ＣＨ３
これまで、抗菌活性及び抗ウイルス活性以外の薬理活性
は全く知られていなかった。n: R=CH3 Until now, no pharmacological activities other than antibacterial and antiviral activities were known.
ロイコトリエン（ＬＴｓ）はエイコサノイドで、アラキ
ドン酸の ５−リポキシゲナーゼ代謝物であり、ＬＴＡ
４．ＬＴＢ４．ＬＴＣ，、ＬＴＤ。Leukotrienes (LTs) are eicosanoids, 5-lipoxygenase metabolites of arachidonic acid, and LTA
4. LTB4. LTC,, LTD.
及びＬ Ｔ Ｅ ４を含む。このうち、ＬＴＣ４゜Ｌ
Ｔ Ｄ ａ及びＬ Ｔ Ｅ ４には気管支平滑収縮作用
、細動脈収縮作用、血管透過性亢進作用があることが知
られている。and LTE4. Of these, LTC4゜L
It is known that T Da and L T E 4 have bronchial smoothing constriction effects, arteriolar constriction effects, and vascular permeability enhancement effects.
また、トロンボキサン（ＴＸ）Ａ２もアラキドン酸代謝
物の一つであり、アラキドン酸からシクロオキシゲナー
ゼによりプロスタグラシンＧ２／プロスタグランジンＨ
２が生成されトロンボキサンＡ合成酵素によりＴＸＡ２
に変換される。ＴＸＡ２は血小板凝集、動脈収縮、気管
支収縮という強力な生物活性を有する。In addition, thromboxane (TX) A2 is also one of the arachidonic acid metabolites, and prostaglasin G2/prostaglandin H is synthesized from arachidonic acid by cyclooxygenase.
2 is generated and converted into TXA2 by thromboxane A synthase.
is converted to TXA2 has potent biological activities such as platelet aggregation, arterial constriction, and bronchoconstriction.
このように、ＬＴｓ及びＴＸＡ２は気管支平滑筋収縮作
用等をもつため、例えば気管支喘息やアナフィラキシ−
の病因の一つに数えられている（室田誠逸編集、ロイコ
トリエンと病態（医学書院） ｆ１９８７））。In this way, LTs and TXA2 have a bronchial smooth muscle contraction effect, so they are effective in, for example, bronchial asthma and anaphylaxis.
(Edited by Seiichi Murota, Leukotrienes and Pathology (Igaku Shoin) f1987)).
本発明は、前記構造式を有するチャイネシンを有効成分
とするアレルギー性疾患治療剤を提供する。詳しくは、
ケミカルメデイエータ−としてロイコトリエン及び／又
はトロンボキサンＡ２がアレルギー関連細胞から放出さ
れて発症するＩ型アレルギー性疾患、例えば気管支喘息
、アナフィラキシ−などの治療剤として使用することが
できる。The present invention provides a therapeutic agent for allergic diseases containing chinesin having the above structural formula as an active ingredient. For more information,
As a chemical mediator, leukotriene and/or thromboxane A2 can be used as a therapeutic agent for type I allergic diseases caused by release from allergy-related cells, such as bronchial asthma and anaphylaxis.
本発明の治療剤の有効成分であるチャイネシンとしては
、Ｊｐｔｒｉｕ＋ｍ ｃｈｉｎｔｎｓｅ Ｌの花を
出発原料とし、例えばＭ、Ｎａｇａｉ とＭ、Ｔａｄａ
の方法（前記文献参照）に従って、メタノール抽出、酢
酸エチル／水による分配抽出、酢酸エチル層のシリカゲ
ルクロマトグラフィーで処理することにより得られるチ
ャイネシンＩとチャイネシン■の混合物が、又はこの混
合物をさらに高速液体クロマトグラフィーに掛けて分離
したチャイネシンエ又はチャイネシン■が使用される。The starting material for chinesin, which is an active ingredient of the therapeutic agent of the present invention, is the flower of Jptriu+m chintnse L, such as M, Nagai and M, Tada.
A mixture of chinesin I and chinesin II obtained by methanol extraction, partition extraction with ethyl acetate/water, and silica gel chromatography of the ethyl acetate layer according to the method of Chinesin A or Chinesin II separated by chromatography is used.
混合物として使用する場合、チャイネシンＩとチャイネ
シン■の混合比は特に限定されない。When used as a mixture, the mixing ratio of Chinesin I and Chinesin II is not particularly limited.
チャイネシンの急性毒性はＬＤｓｏ３〜１０■／ｋｇ（
マウス、静脈内投与）である。The acute toxicity of chinesin is LDso3~10■/kg (
mice, intravenous administration).
本発明の治療剤は、好ましくは経口投与又は吸入投与さ
れるが、緊急を要する場合には皮下、筋肉もしくは静脈
内投与することも可能である。しかし、投与方法には限
定されない。The therapeutic agent of the present invention is preferably administered orally or by inhalation, but in urgent cases it can also be administered subcutaneously, intramuscularly or intravenously. However, the method of administration is not limited.
本発明の治療剤は、アレルギー性疾患の治療を必要とす
る患者に対して、患者当たりチャイネシン１〜１０００
■の用量範囲で一般に数回に分けて１日当たりチャイネ
シン３〜３０００■の全日用量で投与することができる
。もちろん、その投与量は患者の体重、症状及び当業者
が認めるその他の因子によって変化させることができる
。The therapeutic agent of the present invention is administered to patients in need of treatment for allergic diseases at doses of 1 to 1000 chinesin per patient.
A total daily dose of 3 to 3000 ml of chinesin per day can generally be administered in several divided doses. Of course, the dosage can vary depending on the patient's weight, symptoms, and other factors recognized by those skilled in the art.
本発明の治療剤は、有効成分チャイネシンに加えて、医
薬上許容し得るベヒクル、担体、賦形剤、結合剤、防腐
剤、安定剤、香味剤などとともに一般的に認められた製
薬実施に要求される単位用量形態で混和される。これら
の組成物又は製剤中のチャイネシンの量は、指示された
範囲の適当な用量が得られるように決められる。また、
本発明の治療剤の形態としては、例えば錠剤、カプセル
剤、散剤、吸入液、注射液などが挙げられる。In addition to the active ingredient chinesin, the therapeutic agents of the present invention contain pharmaceutically acceptable vehicles, carriers, excipients, binders, preservatives, stabilizers, flavoring agents, etc. as required by generally accepted pharmaceutical practice. Admixed in unit dosage form. The amount of chinesin in these compositions or formulations is determined to provide a suitable dosage within the indicated range. Also,
Examples of the form of the therapeutic agent of the present invention include tablets, capsules, powders, inhalation solutions, and injection solutions.
以下の実施例により、本発明をさらに詳細に説明する。The following examples illustrate the invention in further detail.
（実施例）
ロイコトリエン拮抗作用
モルモットから摘出した気管の膜様部対側を切開した後
、走行に対し垂直に一分節ずつ切り離し、３個を連続し
てインドメタンン１０−６Ｍを含む３７℃のタイロード
液（ＮａＣ１：１３７ｍＭ、 ＫＣＩ：２．７ｍＭ、Ｃ
ａＣｌ２１．８Ｊ、Ｍｇｃ１２：１．ＩｍＭ、ＮａＨＰ
Ｏ，： ［１，４ｍＭ、 ＮａＨＣＯ３１２、ＯｍＭ、
グルＤ−ス：５．６ｍＭ）を満たしたマグヌス管に
０．５ｇの負荷を掛けて懸垂した。マグヌス管中には９
５％０□−５％ＣＯ２混合ガスを通気し、平滑筋の収縮
を等張トランスデユーサ−（ＴＤ−１１２８、日本光電
）を介してポリグラフ（ＩＤ−１１２３，日本光電）上
に記録した。被験薬はロイコトリエン（ＬＴ） Ｄ４
（Ｃａｙｍｘｎ Ｃｈｅｎ＋１ｃａｌ） ３Ｘ１Ｇ−
８Ｍ添加前に２０分間インキュベートした。結果を第１
表に示す。(Example) Leukotriene antagonism After incising the opposite side of the membranous part of the trachea isolated from a guinea pig, one segment was cut out perpendicular to the travel direction, and three pieces were successively heated at 37°C containing 10-6M indomethane. Tyrode's solution (NaC1: 137mM, KCI: 2.7mM, C
aCl21.8J, Mgc12:1. ImM, NaHP
O,: [1,4mM, NaHCO312, OmM,
A load of 0.5 g was applied to a Magnus tube filled with Glucose (5.6 mM) and suspended. 9 in the Magnus tube
A mixed gas of 5% 0□-5% CO2 was aerated, and smooth muscle contractions were recorded on a polygraph (ID-1123, Nihon Kohden) via an isotonic transducer (TD-1128, Nihon Kohden). The test drug is leukotriene (LT) D4
(Caymxn Chen+1cal) 3X1G-
Incubated for 20 minutes before adding 8M. Results first
Shown in the table.
トロンボキサンＡ２拮抗作用
モルモットから摘出した気管の膜様部対側を切開した後
、走行に対し垂直に一分節ずつ切り離し、３個を連続し
て３７℃のタイロード液を満たしたマグヌス管に（１，
５ｇの負荷を掛けて懸垂した。マグヌス管中には９５％
０２−５％ＣＯ２混合ガスを通気し、平滑筋の収縮を上
記と同様に記録した。被験薬は安定型トロンボキサンＡ
２Ｕ４６６１９（９，１１ジデオキシ−９ａ、１ｌａ−
メタノエポキシ−ＰＧＦ２．。Thromboxane A2 Antagonism After making an incision on the contralateral side of the membranous part of the trachea isolated from a guinea pig, cut out one segment at a time perpendicular to the travel direction, and place three pieces in succession into a Magnus tube filled with Tyrode's solution at 37°C ( 1,
The patient was suspended with a load of 5 g. 95% in the Magnus tube
A 02-5% CO2 gas mixture was vented and smooth muscle contractions were recorded as described above. The test drug is stable thromboxane A.
2U46619 (9,11 dideoxy-9a, 1la-
Methanoepoxy-PGF2. .
Ｃａｂｍａｎ Ｃｈｅｍｉｃａｌ） ３ｘ １０−８Ｍ
添加前に２０分間インキュベートした。対照薬物はトロ
ンボキサン類似体であるピナントロンボキサン（ＰＴ）
Ａ２（Ｃａｙｍｌｎ Ｃｈｅ口１ｃａｌ）を使用した。Cabman Chemical) 3x 10-8M
Incubated for 20 minutes before addition. The control drug is the thromboxane analog pinanthromboxane (PT).
A2 (Caymln Che mouth 1 cal) was used.
結果を同じく第１表に示す。The results are also shown in Table 1.
第 被験薬 （濃度） チャイネシン− （２，３Ｘ １Ｇ−’Ｍ＋ ＰＴＡ。No. Test drug (concentration) chinesin (2,3X 1G-'M+ P.T.A.
（３ｘ １０−８Ｍ） Ｆ Ｐ Ｌ ５５７１２−８） （ＩＸｌｆｌ−５Ｍ） ネ） 平均±Ｓε ％阻害 ＬＴＤ。(3x 10-8M) F P 55712-8) (IXlfl-5M) N) Average ±Sε % inhibition LTD.
Ｕ ４６６１９
９４．５±５
６５５±９
４±２
（文献値）
（Ｎ＝３）
零ネ）
木本本）
Ｍ、ＮＢｘｉ とＭ、 Ｔａｄａ、 ＣＨＥＭＩＳＴ
ＲＹ ＬＥＴＴＥＲ３゜ｐｐ、ｌ３３７−１３４０．
１９８７に記載の方法に従って単離した。チャイネシン
Ｉ／チャ
イネシンＩＩ ＝ ７０／ ３０ （Ｗ／Ｗ）Ｒ，Ｄ、
Ｋｒｅｌｌ ら、 Ｐ＋ｏｓｔａｇｌａｎｄｉｎｓ、
２２：３８？−４０９，１９８１からの文献値。U 46619 94.5±5 655±9 4±2 (Literature value) (N=3) Zerone) Kimotomoto) M, NBxi and M, Tada, CHEMIST
RY LETTER3゜pp, l337-1340.
It was isolated according to the method described in 1987. Chinesin I/Chinesin II = 70/30 (W/W) R, D,
Krell et al., P+ostaglandins,
22:38? -409, literature value from 1981.
ＦＰＬ５５７１２ ： ｓｏｄｉＩｌｍ ７−［３−（
４−ａｃｅｌｙｌ−３−ｈ７ｄｒｏＢ−２−ｐｒｏｐ７
１ｐｈｅｎｏｘ７）−２−ｈ！ｄｒｏｘ７ｐｒｏｐ７１
］−４−ｏｘｏ−８−ｐ＋ｏｐ７１−４８−ｃｈ＋ｏｍ
ｅｎｅ２−ｃａｒｂｏｘ７１ａｌｅ０
第１表から、チャイネシンはロイコトリエン又はトロン
ボキサンＡ２拮抗作用をともに有することが判明した。FPL55712: sodiIlm 7-[3-(
4-acelyl-3-h7droB-2-prop7
1phenox7)-2-h! drox7prop71
]-4-oxo-8-p+op71-48-ch+om
ene2-carbox71ale0 From Table 1, it was found that chinesin has both leukotriene and thromboxane A2 antagonistic effects.
（発明の効果）
本発明の治療剤の有効成分であるチャイネシンは、アレ
ルギー性疾患におけるケミカルメデイエータ−であるロ
イコトリエン又はトロンボキサンＡ２のレセプターに対
しこれらのメデイエータ−と強く拮抗することから、ア
レルギー性疾患の治療に有効に使用し得る。(Effects of the Invention) Chinesin, which is an active ingredient of the therapeutic agent of the present invention, strongly antagonizes the receptors of leukotriene or thromboxane A2, which are chemical mediators in allergic diseases, and therefore is effective against allergic diseases. It can be effectively used to treat diseases.
Claims (3)
チャイネシンを有効成分とするアレルギー性疾患治療剤
。(1) A therapeutic agent for allergic diseases containing chinesin as an active ingredient, which has the following structural formula: ▲Mathematical formula, chemical formula, table, etc.▼ (In the formula, R represents a methyl group or an ethyl group).
疾患であることを特徴とする請求項１に記載のアレルギ
ー性疾患治療剤。(2) The therapeutic agent for allergic disease according to claim 1, wherein the allergic disease is a disease caused by type I allergy.
シーである請求項２に記載のアレルギー性疾患治療剤。(3) The therapeutic agent for allergic disease according to claim 2, wherein the allergic disease is bronchial asthma or anaphylaxis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11137090A JPH049329A (en) | 1990-04-26 | 1990-04-26 | Remedy for allergic disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11137090A JPH049329A (en) | 1990-04-26 | 1990-04-26 | Remedy for allergic disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH049329A true JPH049329A (en) | 1992-01-14 |
Family
ID=14559474
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11137090A Pending JPH049329A (en) | 1990-04-26 | 1990-04-26 | Remedy for allergic disease |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH049329A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003053456A1 (en) * | 2001-12-21 | 2003-07-03 | Phenion Gmbh & Co. Kg | Use of hyperforin or st john's wort extracts against anaphylactic states of shock and for maintaining and improving bone health |
| CN103288615A (en) * | 2013-06-27 | 2013-09-11 | 中国科学院昆明植物研究所 | Monocyclic phloroglucinol compounds and pharmaceutical composition and application thereof |
-
1990
- 1990-04-26 JP JP11137090A patent/JPH049329A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003053456A1 (en) * | 2001-12-21 | 2003-07-03 | Phenion Gmbh & Co. Kg | Use of hyperforin or st john's wort extracts against anaphylactic states of shock and for maintaining and improving bone health |
| CN103288615A (en) * | 2013-06-27 | 2013-09-11 | 中国科学院昆明植物研究所 | Monocyclic phloroglucinol compounds and pharmaceutical composition and application thereof |
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