JPS63233917A - Immunosuppressive agent - Google Patents
Immunosuppressive agentInfo
- Publication number
- JPS63233917A JPS63233917A JP6779887A JP6779887A JPS63233917A JP S63233917 A JPS63233917 A JP S63233917A JP 6779887 A JP6779887 A JP 6779887A JP 6779887 A JP6779887 A JP 6779887A JP S63233917 A JPS63233917 A JP S63233917A
- Authority
- JP
- Japan
- Prior art keywords
- cells
- glycoside
- flavonoid compound
- active ingredient
- immunosuppressive agent
- 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.)
- Granted
Links
- 239000003018 immunosuppressive agent Substances 0.000 title claims abstract description 8
- 229940125721 immunosuppressive agent Drugs 0.000 title abstract description 4
- 229930182470 glycoside Natural products 0.000 claims abstract description 13
- 150000002338 glycosides Chemical class 0.000 claims abstract description 13
- -1 flavonoid compound Chemical class 0.000 claims abstract description 9
- 229930003935 flavonoid Natural products 0.000 claims abstract description 7
- 235000017173 flavonoids Nutrition 0.000 claims abstract description 7
- 239000004480 active ingredient Substances 0.000 claims abstract description 5
- 229960003444 immunosuppressant agent Drugs 0.000 claims description 4
- 230000001861 immunosuppressant effect Effects 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 17
- IKMDFBPHZNJCSN-UHFFFAOYSA-N Myricetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC(O)=C(O)C(O)=C1 IKMDFBPHZNJCSN-UHFFFAOYSA-N 0.000 abstract description 11
- PCOBUQBNVYZTBU-UHFFFAOYSA-N myricetin Natural products OC1=C(O)C(O)=CC(C=2OC3=CC(O)=C(O)C(O)=C3C(=O)C=2)=C1 PCOBUQBNVYZTBU-UHFFFAOYSA-N 0.000 abstract description 11
- 235000007743 myricetin Nutrition 0.000 abstract description 11
- 229940116852 myricetin Drugs 0.000 abstract description 11
- 210000001744 T-lymphocyte Anatomy 0.000 abstract description 5
- IYRMWMYZSQPJKC-UHFFFAOYSA-N kaempferol Chemical compound C1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 IYRMWMYZSQPJKC-UHFFFAOYSA-N 0.000 abstract description 4
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 abstract description 4
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 abstract description 3
- UBSCDKPKWHYZNX-UHFFFAOYSA-N Demethoxycapillarisin Natural products C1=CC(O)=CC=C1OC1=CC(=O)C2=C(O)C=C(O)C=C2O1 UBSCDKPKWHYZNX-UHFFFAOYSA-N 0.000 abstract description 2
- YXOLAZRVSSWPPT-UHFFFAOYSA-N Morin Chemical compound OC1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 YXOLAZRVSSWPPT-UHFFFAOYSA-N 0.000 abstract description 2
- 150000008195 galaktosides Chemical class 0.000 abstract description 2
- 229930182478 glucoside Natural products 0.000 abstract description 2
- 150000008131 glucosides Chemical class 0.000 abstract description 2
- 230000036039 immunity Effects 0.000 abstract description 2
- 230000016784 immunoglobulin production Effects 0.000 abstract description 2
- 230000005764 inhibitory process Effects 0.000 abstract description 2
- 235000008777 kaempferol Nutrition 0.000 abstract description 2
- 210000004698 lymphocyte Anatomy 0.000 abstract description 2
- 235000007708 morin Nutrition 0.000 abstract description 2
- XHEFDIBZLJXQHF-UHFFFAOYSA-N fisetin Chemical compound C=1C(O)=CC=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 XHEFDIBZLJXQHF-UHFFFAOYSA-N 0.000 abstract 2
- JVXZRQGOGOXCEC-UHFFFAOYSA-N scutellarein Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C(O)=C(O)C=C2O1 JVXZRQGOGOXCEC-UHFFFAOYSA-N 0.000 abstract 2
- SCZVLDHREVKTSH-UHFFFAOYSA-N 4',5,7-trihydroxy-3'-methoxyflavone Chemical compound C1=C(O)C(OC)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 SCZVLDHREVKTSH-UHFFFAOYSA-N 0.000 abstract 1
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 abstract 1
- UOSZQIQUCYTISS-UHFFFAOYSA-N chrysoeriol Natural products C1=C(O)C(C)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 UOSZQIQUCYTISS-UHFFFAOYSA-N 0.000 abstract 1
- 230000004069 differentiation Effects 0.000 abstract 1
- 235000011990 fisetin Nutrition 0.000 abstract 1
- 229930182479 fructoside Natural products 0.000 abstract 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 1
- 238000002054 transplantation Methods 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 30
- 238000004519 manufacturing process Methods 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 8
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 4
- 210000000822 natural killer cell Anatomy 0.000 description 4
- 230000001629 suppression Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 3
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 3
- DANYIYRPLHHOCZ-UHFFFAOYSA-N 5,7-dihydroxy-4'-methoxyflavone Chemical compound C1=CC(OC)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 DANYIYRPLHHOCZ-UHFFFAOYSA-N 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- 101000981253 Mus musculus GPI-linked NAD(P)(+)-arginine ADP-ribosyltransferase 1 Proteins 0.000 description 2
- 230000000961 alloantigen Effects 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- RTIXKCRFFJGDFG-UHFFFAOYSA-N chrysin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=CC=C1 RTIXKCRFFJGDFG-UHFFFAOYSA-N 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- WCNLFPKXBGWWDS-UHFFFAOYSA-N datiscetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=CC=C1O WCNLFPKXBGWWDS-UHFFFAOYSA-N 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- PXDJXZJSCPSGGI-UHFFFAOYSA-N palmityl palmitate Chemical compound CCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC PXDJXZJSCPSGGI-UHFFFAOYSA-N 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- NYCXYKOXLNBYID-UHFFFAOYSA-N 5,7-Dihydroxychromone Natural products O1C=CC(=O)C=2C1=CC(O)=CC=2O NYCXYKOXLNBYID-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 1
- QAGGICSUEVNSGH-UHFFFAOYSA-N Diosmetin Natural products C1=C(O)C(OC)=CC=C1C1=CC(=O)C2=CC=C(O)C=C2O1 QAGGICSUEVNSGH-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical class C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000646 Interleukin-3 Human genes 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 235000009962 acacetin Nutrition 0.000 description 1
- OVVGHDNPYGTYIT-ROUHPGRKSA-N alpha-L-Rhap-(1->6)-D-Glcp Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 OVVGHDNPYGTYIT-ROUHPGRKSA-N 0.000 description 1
- 230000003409 anti-rejection Effects 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
- 230000024245 cell differentiation Effects 0.000 description 1
- 235000015838 chrysin Nutrition 0.000 description 1
- 229940043370 chrysin Drugs 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 235000015428 diosmetin Nutrition 0.000 description 1
- MBNGWHIJMBWFHU-UHFFFAOYSA-N diosmetin Chemical compound C1=C(O)C(OC)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 MBNGWHIJMBWFHU-UHFFFAOYSA-N 0.000 description 1
- 229960001876 diosmetin Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229940076264 interleukin-3 Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 235000009498 luteolin Nutrition 0.000 description 1
- LRDGATPGVJTWLJ-UHFFFAOYSA-N luteolin Natural products OC1=CC(O)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 LRDGATPGVJTWLJ-UHFFFAOYSA-N 0.000 description 1
- IQPNAANSBPBGFQ-UHFFFAOYSA-N luteolin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(O)C(O)=C1 IQPNAANSBPBGFQ-UHFFFAOYSA-N 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 210000003810 lymphokine-activated killer cell Anatomy 0.000 description 1
- 201000006512 mast cell neoplasm Diseases 0.000 description 1
- 208000006971 mastocytoma Diseases 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Pyrane Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
産業上の利用分野
本発明は、一般式
（式中Ｒ１ないしＲ９は−Ｈ，−ＯＨ，−ＯＣＨ，’ｉ
示す）で表わされるフラボノイド化合物又はこれらの配
糖体を有効成分とする免疫抑制剤に関するものである。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention is directed to the general formula (wherein R1 to R9 are -H, -OH, -OCH, 'i
The present invention relates to an immunosuppressant containing a flavonoid compound represented by (shown) or a glycoside thereof as an active ingredient.
最近有効な免疫抑制剤として、サイクロスホリンＡが使
用されはじめ、従来のアゾチオプリンとプレドニゾロン
の併用法に比べ、移植臓器の生着率がさらに改善されて
いる。しかしながら１サイクロス？リンＡの使用に伴う
合併症は少なくない。Cyclosphorin A has recently begun to be used as an effective immunosuppressant, and the survival rate of transplanted organs has been further improved compared to the conventional combination of azothiopurine and prednisolone. However, 1 Cyclos? There are many complications associated with the use of phosphorus A.
特に、サイクロスポリンＡの使用による腎障害の多発が
新たな問題となっている〔たとえば臨床免疫、第１４巻
、第８３７頁（１９８２） 参照〕。今後腎移植など
をはじめとする臓器移植に対する期待はますます高まる
と考えられ、それゆえさらに副作用の少ない、有効な拒
絶反応抑制剤を開発する必要があった。In particular, frequent renal damage caused by the use of cyclosporin A has become a new problem [see, for example, Clinical Immunology, Vol. 14, p. 837 (1982)]. It is thought that expectations for organ transplants, including kidney transplants, will continue to rise in the future, and therefore there is a need to develop effective anti-rejection drugs with even fewer side effects.
問題点を解決する手段、作用及び効果
本発明者らは、フラダノイド化合物又はこれらの配糖体
が試験管内（ｉｎ ｖｉｔｒｏ ） の研究において
、抗体産生、リンパ球混合培養疋よるＴ細胞の増殖とキ
ラーで細胞の分化を抑制する効果を有し、移植免疫など
に適用可能な免疫抑制剤であることを見出し、本発明を
完成するに至った。Means for Solving the Problems, Actions, and Effects The present inventors have found that, in in vitro studies, fladanoid compounds or their glycosides have been shown to induce antibody production, proliferation of T cells by lymphocyte mixed culture, and killer killer cells. The present inventors have discovered that the present invention is an immunosuppressant that has the effect of suppressing cell differentiation and can be applied to transplant immunity, etc., and have completed the present invention.
本発明に用いるフラゲノイド化合物は構造式＝（式中Ｒ
１ないしＲ９は同一でも異なってもよくかつそれぞれ−
Ｈ，−０Ｈ４たは一０ＣＦＩ３ｔ−示す）を有するもの
である。これらの７うざノイド化合物としては、たとえ
ばミリセチン、 モリン、 ケンフェロール、 フイセ
チン、 ダチスセチン。The flagenoid compound used in the present invention has a structural formula = (where R
1 to R9 may be the same or different and each -
H, -0H4 or -0CFI3t-). These seven usanoid compounds include, for example, myricetin, morin, kaempferol, fuisetin, and datiscetin.
ロピネチン、 ヘルパセテン２ ケルセタｒチン。Ropinetine, herpaceten 2, querceta rtin.
ヒビスチン、 アラビノ、 プラトール、 クリシン、
アビゲニン、 アカセチン、 ルテオリン、 ジオス
メチン、 スフテラレイン、 タリンエリオールなどが
挙げられる。またこれらの配糖体を形成する糖成分はい
ずれのものでもよく、たとえば配糖体としてはグルコシ
ド・ ガラクトシド、 フルクシド、 ラムノシト、
ラムノグルコシド、 アラビノシト、 キシロシド、
ルチノシドなどが挙げられる。hibistine, arabino, platole, chrysin,
Examples include abigenin, acacetin, luteolin, diosmetin, sufterarein, and talineriol. Furthermore, the sugar component forming these glycosides may be any one; for example, the glycosides include glucoside/galactoside, frucside, rhamnocyto,
rhamnoglucoside, arabinocyto, xyloside,
Examples include rutinoside.
これらのフラゲノイド化合物及び七の配糖体は天然の植
物から９分離精製したものであっても、化学的に合成し
たものであっても、同等の免疫抑制活性を有している。These flagenoid compounds and seven glycosides have equivalent immunosuppressive activity whether they are isolated and purified from natural plants or chemically synthesized.
本発明の免疫抑制剤は特に移植免疫反応の抑制に有効で
あり、免疫担当細胞の機能抑制、すなわちエフェクター
細胞の生成を抑制する。宿主から移植片に対する拒絶反
応の抑制効果としては、たとえはアロ抗原に対する細胞
障害性Ｔ細胞の生成抑制、遅延型過敏症に関与するエフ
ェクター細胞の生成抑制、ナナユラルキラー細胞、リン
ホカイン活性化キラーイ１１］胞の生成抑制、インター
ロイキン−２、インターロイキン−３などのリンホカイ
ン生成及び放出の抑制、リン／ぐ球混合反応（ＭＬＲ）
の抑制などがある。また移植片から宿主への免疫反応の
抑制としては、列えは移植片対宿主免疫反応（ＧＶＨＲ
） の抑制かある。The immunosuppressive agent of the present invention is particularly effective in suppressing transplant immune reactions, and suppresses the function of immunocompetent cells, that is, suppresses the production of effector cells. The effect of suppressing the rejection reaction from the host to the graft includes, for example, suppressing the production of cytotoxic T cells against alloantigens, suppressing the production of effector cells involved in delayed-type hypersensitivity, nanatural killer cells, and lymphokine-activated killer cells. suppression of production, suppression of lymphokine production and release such as interleukin-2 and interleukin-3, mixed lymphocytic reaction (MLR)
This includes the suppression of In addition, as a means of suppressing the immune response from the graft to the host, the array is used to suppress the graft-versus-host immune response (GVHR).
) is suppressed.
実施例 以下実施例により本発明をさらに説明する。Example The present invention will be further explained below with reference to Examples.
実施例Ｉ
ＢＸＳＢ ／ＭｐＪ −ｖ ウス（６ケ月令、 離反
ＥＲ）ノ牌細胞とマイトマイシンＣ処理したＢＡＬＢ
／ Ｃマウスの牌細胞を混合し、種々の濃度のミリセチ
ンと共に５日間培養し、アロキラーＴｇｌ胞生成反応に
及ぼすミリセチンの効果を調べた。Example I BXSB/MpJ-v mouse (6 months old, detached ER) tile cells and BALB treated with mitomycin C
/C mouse tile cells were mixed and cultured for 5 days with various concentrations of myricetin to examine the effect of myricetin on the allochilar Tgl cell production reaction.
培養条件はＢＸＳ Ｂ牌細胞５×１０ とＢＡＬＢ ／
Ｃ牌細胞５×１ｏ を各穴て入れ、２−の５僑ウシ胎
仔血清、２ ｍＭのＬ−グルタミン、 ５ Ｘ ｔｏ−
５Ｍの２−メルヵグトエタノールを添加しりＲＰＭＩ
１６４０培養液にて３７°Ｃ，５％炭酸がバー９５係空
気下で培養した。ミ’）セチンは培養開始時点で添加し
、生成したＢＡＬＢ ／ Ｃアロ抗原（Ｉ（−２ｄ）ｔ
−認識するアロキラーＴ細胞の活性を以下の方法で測定
した。Ｈ−２ｄ抗原をもつＰ ８１５マストサイトーマ
細抱を Ｃｒ でラベルし、その１０ 個を５日間
培養した１３ＸＳＢ 細胞３ Ｘ １０”錦と混合し、
９６穴マイクログレートで３７℃、４時間培養した後、
アロキラーで細胞により破壊されたＰ８１５細胞から遊
離される５１Ｃｒ ｆｆｌ：に測定し、破壊活性を５１
ｃｒ量の相対値で表現した。この計算式はっぎのとおり
である。The culture conditions were BXS B tile cells 5 x 10 and BALB/
5 x 10 C tile cells were placed in each well and treated with 2-50% fetal bovine serum, 2mM L-glutamine, 5X to-
RPMI with 5M 2-mercagtoethanol added
The cells were cultured in 1640 culture medium at 37°C under air with 5% carbon dioxide and 95 bars. Mi') Cetin was added at the start of the culture, and the generated BALB/C alloantigen (I(-2d)t
-The activity of recognizing allokiller T cells was measured by the following method. P815 mastocytoma cells carrying H-2d antigen were labeled with Cr, 10 of them were mixed with 3 x 10'' 13XSB cells cultured for 5 days,
After culturing in a 96-well microplate at 37°C for 4 hours,
The destructive activity of 51Cr ffl: released from P815 cells destroyed by Allokiller was determined.
Expressed as a relative value of cr amount. This calculation formula is exactly as shown.
結果を表１に示す。これらの結果が示すとおり、ミリセ
チン濃度９．１ Ｘ ＩＱ”３ ないし９．Ｉ Ｘ
ｔｏ−２μ？／−ではや＼アロ牛歩−細胞生成を増強す
る効果が認められたが、９．１μ？／−では強カｌアロ
キラー細胞生成反応の抑制が認められた。The results are shown in Table 1. As these results show, myricetin concentration is 9.1 × IQ”3 to 9.I
to-2μ? /- So ＼ Aro Ushiho - The effect of enhancing cell production was recognized, but 9.1μ? /-, inhibition of strong potassium allokiller cell production reaction was observed.
表 １
実施例２
実施例１０ミリセチン【代えて、各種のフラゲノイド化
合物を用い、これらの添加濃度９．１μｆ／−における
アロキラーＴ細胞生成反応に及ぼすフラぎノイド化合物
の効果を調べた。Table 1 Example 2 Example 10 Myricetin [Instead, various flagenoid compounds were used to investigate the effects of the flagenoid compounds on the Alokiller T cell production reaction at a concentration of 9.1 μf/-.
この結果を表２に示す。The results are shown in Table 2.
実施例３
実ＭＭ例Ｉのミリセチンに代えて、各種のフラ♂ノイド
化合物の配糖体を用い、これらの添加濃度９．１μｔ／
−におけるアロキラーＴ細胞生成反応に及ぼすフラメノ
イド化合物の効果を調べた。Example 3 Instead of myricetin in Actual MM Example I, glycosides of various furanoid compounds were used, and the concentration of these added was 9.1 μt/
The effect of flamenoid compounds on the allokiller T cell production reaction in - was investigated.
この結果を表３に示す。The results are shown in Table 3.
表 ３
実施ｆｐＩＪ４
ＢＸＭＢ ／ＭｐＪ ？ ウス（６ケ月令、雌及び雄）
の牌細胞とマイトマイシンＣ処理したＢＡＬＢ ／ Ｃ
マウスの牌細胞２×１０ 個を９６穴マイクログレート
の各人に入れ、０．２−の５−ウシ胎仔血清、２−のＬ
−グルタミン、５ＸＩＯＭの２−メルカプトエタノール
を添加したＲＰＭＩ １６４０培養液にて３７６Ｃ，５
％炭酸がグー９５チ空気下で３日間培養後、各穴に０．
２ＡＣｉ（キューリー）のＨ−チミジンを加えて２時間
培養し、セルフ１−ベスターで細胞を回収し、 Ｈ−チ
ミジンの細胞内への取り込み量（壊変毎分、 ｄ、ｐ
、ｍ、と表示する）ｆｔ測定し、ＤＮＡ合成の程度を調
べた。Table 3 Implementation fpIJ4 BXMB /MpJ? Mouse (6 months old, female and male)
tile cells and mitomycin C-treated BALB/C
2 x 10 mouse tile cells were placed in each 96-well microplate and incubated with 0.2-5-fetal bovine serum, 2-L
- Glutamine, 376C,5 in RPMI 1640 medium supplemented with 5XIOM of 2-mercaptoethanol.
After incubation for 3 days under air, the carbon dioxide concentration was 95%.
2ACi (Curie) of H-thymidine was added and cultured for 2 hours, and the cells were collected using Self-1-Bester, and the amount of H-thymidine taken into the cells (disintegration per minute, d, p
, m, ) ft was measured to examine the extent of DNA synthesis.
この結果を表４に示す。ミリセチンの濃度が９、Ｉ Ｘ
１０”μｔ／−でＤＮＡ合成の抑制効果が認められは
じめ、９．１μｆ／−では顕著な抑制効果が認められた
。The results are shown in Table 4. The concentration of myricetin is 9, I
At 10"μt/-, an inhibitory effect on DNA synthesis began to be observed, and at 9.1μf/-, a significant inhibitory effect was observed.
実施例５
ＢＸＳＢ ／ ＭＰＪ マウス（４ケ月令、雌）の牌
細胞５×１０ 個と ｃｒ ラベルしたＹＡＣ−１リ
ンホーマ細胞（マウスＮＫ細胞の標的細胞）１０個を混
合し、撞々の濃度のＳ ＩＪ七チンと共に９６穴マイク
ロ！レートで３７°０．４時間培養後、ＮＫ細胞によ抄
破壊されたＹＡＣ−１細胞から遊離された５１ｃｒ ｉ
を測定することにより、ＮＫ細胞の標的細胞破壊反応活
性に及ぼすミ’）セチンの効果を調べた。ＮＫ活性の強
さを表現する計算式は実施例１の式を用いた。Example 5 5 x 10 tile cells of a BXSB/MPJ mouse (4 months old, female) and 10 cr-labeled YAC-1 lymphoma cells (target cells of mouse NK cells) were mixed and S 96 hole micro with IJ seven chin! After culturing at 37°C for 0.4 hours, 51cri released from YAC-1 cells that had been disrupted by NK cells.
The effect of mi')cetin on the target cell destruction reaction activity of NK cells was investigated by measuring. The formula used in Example 1 was used to express the strength of NK activity.
この結果を表５に示す。ミリセチンの濃度０．５μｔｌ
ｒｄＱ上でＮＫ活性の抑制効果が認められた。The results are shown in Table 5. Myricetin concentration 0.5μtl
A suppressive effect on NK activity was observed on rdQ.
表 ５
実施例６
実ｍ例６のミリセチンに代えて、各種のフラゲノイド化
合物及びぞの配糖体を用い、これらの添加濃度１．２５
μｆ／−におけるＮＫ細胞の標的細胞破壊反応に及ぼす
効果を調べた。この結果を表６に示す。Table 5 Example 6 In place of myricetin in Example 6, various flagenoid compounds and their glycosides were used, and their concentration was 1.25.
The effect of μf/- on the target cell destruction reaction of NK cells was investigated. The results are shown in Table 6.
表 ６
実施例７
実施例１と同じ条件で５日間のリン・９球混合培養を行
ない、生成する抗Ｈ−２ｄ（ＢＡＬＢ／Ｃ）”ＤＴＨ細
胞の活性を調べた。Ｔ０□□ 活性はフレッシュなりＡ
ＬＢ ／ Ｃ１１１９細胞１×１０ 個と培養細胞３ｘ
１ 個を混合し、３０μ乙 のイーグルＭＩＥＭ培
養液に懸濁し、ＢＡＬＢ ／ Ｃマウスの定確に注射し
、２４時間後の足踏の肥厚をノギスで測定した。遅延型
過敏症反応の程度を足踏の肥大で評価した。Table 6 Example 7 A mixed culture of Rin and 9 cells was carried out for 5 days under the same conditions as in Example 1, and the activity of the generated anti-H-2d (BALB/C)"DTH cells was investigated. Nari A
Culture cells 3x with 1 x 10 LB/C1119 cells
1 was mixed, suspended in 30μ of Eagle's MIEM culture solution, and precisely injected into BALB/C mice, and 24 hours later, the thickening of the foot was measured using a caliper. The degree of delayed hypersensitivity reaction was evaluated by hypertrophy of foot stepping.
ミリセチン濃度１０．０μｆ／−で著明なＴＤＴＨ生成
反応の抑制が認められた。Significant suppression of the TDTH production reaction was observed at a myricetin concentration of 10.0 μf/−.
Claims (1)
かつそれぞれ−Ｈ、−ＯＨまたは−ＯＣＨ＿３を示す）
で表わされるフラボノイド化合物又はこれらの配糖体を
有効成分とする免疫抑制剤。[Claims] General formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1 to R_9 may be the same or different and each represents -H, -OH or -OCH_3)
An immunosuppressant containing a flavonoid compound or a glycoside thereof as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62067798A JP2544734B2 (en) | 1987-03-24 | 1987-03-24 | Immunosuppressant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62067798A JP2544734B2 (en) | 1987-03-24 | 1987-03-24 | Immunosuppressant |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63233917A true JPS63233917A (en) | 1988-09-29 |
| JP2544734B2 JP2544734B2 (en) | 1996-10-16 |
Family
ID=13355329
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62067798A Expired - Fee Related JP2544734B2 (en) | 1987-03-24 | 1987-03-24 | Immunosuppressant |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2544734B2 (en) |
Cited By (11)
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|---|---|---|---|---|
| EP1429750A2 (en) * | 2001-09-06 | 2004-06-23 | Synorx, Inc. | Inhibition by 3-deoxyflavonoids of t-lymphocyte activation and therapies related thereto |
| US7323171B2 (en) | 1991-10-07 | 2008-01-29 | Astellas Us Llc | Methods of treating skin conditions using inhibitors of the CD2/LFA-3 interaction |
| JP2009024023A (en) * | 2008-09-11 | 2009-02-05 | Oriza Yuka Kk | Lipoxygenase inhibitor |
| US7662921B2 (en) | 2004-05-07 | 2010-02-16 | Astellas Us Llc | Methods of treating viral disorders |
| JP2010215580A (en) * | 2009-03-18 | 2010-09-30 | Taiyo Kagaku Co Ltd | Method for producing immunomodulator |
| CN101891729A (en) * | 2010-07-02 | 2010-11-24 | 广西医科大学 | Method for extracting high-purity rhamnazin from ford nervilia leaf |
| US7858095B2 (en) | 2001-07-24 | 2010-12-28 | Astellas Us Llc | Method for treating or preventing sclerotic disorders using CD-2 binding agents |
| CN102344475A (en) * | 2010-07-30 | 2012-02-08 | 昆明制药集团股份有限公司 | Scutellarin derivative and preparation method and application thereof |
| CN103374049A (en) * | 2012-04-18 | 2013-10-30 | 昆明制药集团股份有限公司 | Method for preparing 5,6,4'-trihydroxy flavone-7-0-D-glucuronic acid |
| CN103804335A (en) * | 2014-01-22 | 2014-05-21 | 贵州大学 | Nitrogen-containing derivative for myricetin as well as preparation method and purposes of nitrogen-containing derivative |
| JP2019508383A (en) * | 2016-01-15 | 2019-03-28 | ウニベルジテート ハンブルグＵｎｉｖｅｒｓｉｔａｅｔ Ｈａｍｂｕｒｇ | Flavonoid-type compound having O-rhamnosyl residue |
-
1987
- 1987-03-24 JP JP62067798A patent/JP2544734B2/en not_active Expired - Fee Related
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7323171B2 (en) | 1991-10-07 | 2008-01-29 | Astellas Us Llc | Methods of treating skin conditions using inhibitors of the CD2/LFA-3 interaction |
| US7858095B2 (en) | 2001-07-24 | 2010-12-28 | Astellas Us Llc | Method for treating or preventing sclerotic disorders using CD-2 binding agents |
| JP2005504796A (en) * | 2001-09-06 | 2005-02-17 | シノークス インコーポレイテッド | Inhibition of T-lymphocyte activation by 3-deoxyflavonoids and related therapies |
| EP1429750A4 (en) * | 2001-09-06 | 2005-08-03 | Synorx Inc | Inhibition by 3-deoxyflavonoids of t-lymphocyte activation and therapies related thereto |
| EP1429750A2 (en) * | 2001-09-06 | 2004-06-23 | Synorx, Inc. | Inhibition by 3-deoxyflavonoids of t-lymphocyte activation and therapies related thereto |
| US7662921B2 (en) | 2004-05-07 | 2010-02-16 | Astellas Us Llc | Methods of treating viral disorders |
| JP2009024023A (en) * | 2008-09-11 | 2009-02-05 | Oriza Yuka Kk | Lipoxygenase inhibitor |
| JP2010215580A (en) * | 2009-03-18 | 2010-09-30 | Taiyo Kagaku Co Ltd | Method for producing immunomodulator |
| CN101891729A (en) * | 2010-07-02 | 2010-11-24 | 广西医科大学 | Method for extracting high-purity rhamnazin from ford nervilia leaf |
| CN102344475A (en) * | 2010-07-30 | 2012-02-08 | 昆明制药集团股份有限公司 | Scutellarin derivative and preparation method and application thereof |
| CN103374049A (en) * | 2012-04-18 | 2013-10-30 | 昆明制药集团股份有限公司 | Method for preparing 5,6,4'-trihydroxy flavone-7-0-D-glucuronic acid |
| CN103374049B (en) * | 2012-04-18 | 2016-04-06 | 昆药集团股份有限公司 | One prepares 5,6, the method for 4 '-trihydroxyflavone-7-0-D-glucuronic acid |
| CN103804335A (en) * | 2014-01-22 | 2014-05-21 | 贵州大学 | Nitrogen-containing derivative for myricetin as well as preparation method and purposes of nitrogen-containing derivative |
| JP2019508383A (en) * | 2016-01-15 | 2019-03-28 | ウニベルジテート ハンブルグＵｎｉｖｅｒｓｉｔａｅｔ Ｈａｍｂｕｒｇ | Flavonoid-type compound having O-rhamnosyl residue |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2544734B2 (en) | 1996-10-16 |
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