JPH0324012A - Production promoter for interleukin-2 - Google Patents
Production promoter for interleukin-2Info
- Publication number
- JPH0324012A JPH0324012A JP1157327A JP15732789A JPH0324012A JP H0324012 A JPH0324012 A JP H0324012A JP 1157327 A JP1157327 A JP 1157327A JP 15732789 A JP15732789 A JP 15732789A JP H0324012 A JPH0324012 A JP H0324012A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- active ingredient
- phenylethyl
- thiazole
- dihydroimidazo
- 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
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 102000000588 Interleukin-2 Human genes 0.000 title description 7
- 108010002350 Interleukin-2 Proteins 0.000 title description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 4
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 4
- RJPFPRVTDMWNTH-UHFFFAOYSA-N 3,6,6-trimethyl-n-(2-phenylethyl)-5h-imidazo[2,1-b][1,3]thiazole-2-carboxamide Chemical class S1C2=NC(C)(C)CN2C(C)=C1C(=O)NCCC1=CC=CC=C1 RJPFPRVTDMWNTH-UHFFFAOYSA-N 0.000 claims abstract 3
- 102000015696 Interleukins Human genes 0.000 claims 1
- 108010063738 Interleukins Proteins 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 abstract description 6
- 206010028980 Neoplasm Diseases 0.000 abstract description 5
- 201000011510 cancer Diseases 0.000 abstract description 5
- 230000004073 interleukin-2 production Effects 0.000 abstract description 5
- 208000023275 Autoimmune disease Diseases 0.000 abstract description 4
- 208000035143 Bacterial infection Diseases 0.000 abstract description 4
- 208000029462 Immunodeficiency disease Diseases 0.000 abstract description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 abstract description 4
- 208000022362 bacterial infectious disease Diseases 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 230000003449 preventive effect Effects 0.000 abstract description 4
- 230000003612 virological effect Effects 0.000 abstract description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 abstract description 2
- 150000007522 mineralic acids Chemical class 0.000 abstract description 2
- 150000007524 organic acids Chemical class 0.000 abstract description 2
- 235000006408 oxalic acid Nutrition 0.000 abstract description 2
- 230000001737 promoting effect Effects 0.000 abstract description 2
- 235000019260 propionic acid Nutrition 0.000 abstract description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 abstract description 2
- 206010061598 Immunodeficiency Diseases 0.000 abstract 1
- 230000007813 immunodeficiency Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- QWEWLLNSJDTOKH-UHFFFAOYSA-N 1,3-thiazole-2-carboxamide Chemical compound NC(=O)C1=NC=CS1 QWEWLLNSJDTOKH-UHFFFAOYSA-N 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 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
- 206010030124 Oedema peripheral Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 102000055277 human IL2 Human genes 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Landscapes
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、インターロイキン−２産生促進剤に関する。[Detailed description of the invention] [Industrial application field] The present invention relates to an interleukin-2 production promoter.
ヒトインターロイキンー２ （以下、ｒ ＩＬ−２Ｊと
略記する〉は、癌、細菌感染、ウイルス性疾患、免疫不
全症、自己免疫疾患などの治療、予防剤として有用であ
ることが知られている。またＩＬ−２ ’）セブターの
発現を誘導する物質が存在することも知られている（特
開昭６０−１８５７２１号公報）。しかしながら、ＩＬ
−２の産生を促進する物質はあまり知られていない。Human interleukin-2 (hereinafter abbreviated as rIL-2J) is known to be useful as a therapeutic and preventive agent for cancer, bacterial infections, viral diseases, immunodeficiency diseases, autoimmune diseases, etc. It is also known that there is a substance that induces the expression of IL-2') septa (Japanese Unexamined Patent Publication No. 185721/1982). However, I.L.
Substances that promote the production of -2 are not well known.
Ｎ−（２−フエニルエチル）−３．６．６−トリメチル
−５，６−ジヒドロイミダゾ〔２．１ｂ〕チアゾール−
２−カルポキサミドは、ｉｎ ｖｉｔｒｏではマウス陣
細胞での抗ＳＲ［］Ｃ （ｓｈｅｅｐｒｅｄ ｂｌｏｏ
ｄ ｃｅｌｌ，羊赤血球）応答およびＣｏｎＡ（−］ン
カナバリンＡ）誘発増殖反応の冗進作用を示し； ｉｎ
ｖｉｖｏではＳＲＢＣに対して高反応系のマウスにお
いてプラーク形戒細胞（ＰＦＣ）応答を抑制し、ＳＲＢ
Ｃに対して低反応系のマウスにおいてＰＦＣ応答を冗進
させる作用を示し、マウスにおけるＳＲＢＣ誘発遅延型
過敏症（Ｄｅｌａｙｅｄ Ｔｙｐｅ Ｈｙｐｅｒｓａｎ
ｓｉｔｉｖｉｔｙ，ロＴＨ）反応を抑制し、メチル化ヒ
ト血清アルブミン誘発ＤＴｌ＋反応において、低反応系
のマウスの反応を冗進させるが、高反応系のマウスの反
応を抑制する作用を示し、ラットカラゲニン誘発足浮腫
を抑制しないが、関節リウマチのモデルであるアジュバ
ントおよびコラーゲン誘発関節炎の発症を予防する作用
を有することが知られている［ＦｏｕｒｔｈＩｎｔｅｒ
ｎａｔｉｏｎａｌ Ｃｏｎｆｅｒｅｎｃｅ ｏｎ
Ｉｍｍｕｎｏｐｈａｒｍａ−ｃｏｌｏｇｙ， Ｍａｙ
１５−１９． １９８８， Ｏｓａｋａ， Ｊａｐａｎ
， ９ ４頁及び９６頁〕。N-(2-phenylethyl)-3.6.6-trimethyl-5,6-dihydroimidazo[2.1b]thiazole-
2-Carpoxamide has been shown to be effective against anti-SR[]C (sheepred blood) in mouse cells in vitro.
d cell, sheep red blood cell) response and ConA(-]canavalin A)-induced proliferation response; in
In vivo, the plaque-forming cell (PFC) response was suppressed in mice highly responsive to SRBC, and SRB
It exhibits the effect of redundant PFC responses in mice that are hyporesponsive to C.
In the methylated human serum albumin-induced DTl+ response, it exaggerates the response of low-response mice, but suppresses the response of high-response mice, and has the effect of suppressing the response of rat carrageenan-induced DTl+ responses. Although it does not suppress foot edema, it is known to act as an adjuvant in a model of rheumatoid arthritis and to prevent the onset of collagen-induced arthritis [Fourth Inter
national conference on
Immunopharma-cology, May
15-19. 1988, Osaka, Japan
, pp. 94 and 96].
体内におけるＩＬ−２の産生能を高めることにより、癌
、細菌感染、ウィルス性疾患、免疫不全症、自己免疫疾
患などの治療、予防を行なうことは医療上重要なことで
ある。It is medically important to treat and prevent cancer, bacterial infections, viral diseases, immunodeficiency diseases, autoimmune diseases, etc. by increasing the ability to produce IL-2 in the body.
かかる実状において、本発明者らは、前記従来技術に着
目して研究を続けた結果、Ｎ−（２−フェニルエチル）
−３．６．６−トリメチル−５．６−ジヒドロイミダゾ
（２．１−ｂ〕チアゾール−２−カルポキサミドがＩＬ
−２産生促進活性を有することを見い出し、本発明を完
戒したものである。Under such circumstances, the present inventors continued their research focusing on the above-mentioned prior art, and as a result, N-(2-phenylethyl)
-3.6.6-trimethyl-5.6-dihydroimidazo(2.1-b)thiazole-2-carpoxamide is IL
-2 production-promoting activity, and the present invention has been completed.
即チ、本発明は、Ｎ−（２−フエニルエチル）−３．６
．６−トリメチル−５，６−ジヒドロイミダゾ［２，１
−ｂ〕チアゾール−２−カル゛ボキサミドまたはその非
毒性塩を有効成分として含有することを特徴とするＩシ
−２産生促進剤を提供するものである。That is, the present invention provides N-(2-phenylethyl)-3.6
．． 6-trimethyl-5,6-dihydroimidazo[2,1
-b] The present invention provides an I-2 production promoter characterized by containing thiazole-2-carboxamide or a non-toxic salt thereof as an active ingredient.
上記の有効成分は公知の化合物であって、米国特許第４
７３６０３８号明細書に記載の方法により製造できる。The above-mentioned active ingredients are known compounds, and are disclosed in U.S. Pat.
It can be produced by the method described in No. 736038.
前記の非毒性塩としては、薬学的に許容される塩、例え
ば塩酸、硫酸、炭酸、臭化水素酸、リン酸などの無機酸
との塩：酢酸、ブロピオン酸、シュウ酸、酒石酸、リン
ゴ酸、クエン酸、マレイン酸、種々のスルホン酸、アス
パラギン酸、グルタミン酸などの有機酸との塩が挙げら
れる。Said non-toxic salts include pharmaceutically acceptable salts, such as salts with inorganic acids such as hydrochloric acid, sulfuric acid, carbonic acid, hydrobromic acid, phosphoric acid: acetic acid, propionic acid, oxalic acid, tartaric acid, malic acid. , citric acid, maleic acid, various sulfonic acids, aspartic acid, glutamic acid, and other organic acids.
本発明の有効成分は、賦形剤、結合剤、崩壊剤、溶解剤
などの添加剤と共に公知の製剤技術に従って種々の剤型
、例えば錠剤、カプセル剤、散剤、顧粒剤、シロップ剤
、ドライシロップ剤、注射剤などの剤型とすることがで
きる。The active ingredient of the present invention can be prepared in various dosage forms according to known formulation techniques, such as tablets, capsules, powders, granules, syrups, and dry syrups, together with additives such as excipients, binders, disintegrants, and solubilizers. It can be made into a dosage form such as a drug or an injection.
本有効戒分は、通常経口または非経口投与される。本有
効戒分の投与量は、戊人１人当りｌ〜３０■７日の範囲
であり、患者の症状に応じて適宜増減すればよい。This active ingredient is usually administered orally or parenterally. The dosage of this effective precept is in the range of 1 to 30 to 7 days per person, and may be increased or decreased as appropriate depending on the patient's symptoms.
本有効戒分の急性毒性（ＬＤ，。）は、ラットの場合、
雄で６９２■／ｋｇ（経口投与）、雌で５４９ｍｇ／ｋ
ｇ（経口投与）であり、犬（雌）の場合は９ ０ ０ｍ
ｇ／ｋｇ （経口投与）で死亡例がなく、ｉ３５０■／
ｋｇ（経口投与）で半数例が死亡する。The acute toxicity (LD,.) of this effective precept is for rats:
692■/kg (oral administration) for males, 549mg/kg for females
g (oral administration) and 900 m for dogs (female).
g/kg (oral administration), there were no deaths, and i350■/
kg (oral administration), half of the cases will die.
次に、本発明を実施例により説明するが、本発明はこれ
に限定されるものではない。Next, the present invention will be explained by examples, but the present invention is not limited thereto.
実施例１
カプセル剤；
アゾールー２−カルポキサミド
ステアリン酸マグネシウム １．２８コー
ンスターチ １１３． ８ｇの組
成からなる粉末を各々１２０ｍｇづつｌカプセルに充填
してカプセル剤を得た。Example 1 Capsule; Azole-2-carpoxamide magnesium stearate 1.28 Corn starch 113. Capsules were obtained by filling 120 mg each of 8 g of the powder into 1 capsule.
実施例２
リンパ球混合反応におけるＩＬ−２産生に対する作用
１）試験方法
Ｂ＾ＬＢ／ ｃマウス陣細胞（５ｘｌＯ’）を応答細胞
として、Ｘ線照射（３０００ｒａｄ）ＬたＣ５７ロＬ／
６マウス牌細胞（５Ｘ１０’）を刺激細胞として、Ｎ一
（２−フェニルエチル）−３．６．６−｝リメチル−５
．６−ジヒＰロイミダゾ（２，１−ｂ〕チアゾール−２
−カルボキサミド（被験薬〉と共にＬ−グルタミン（２
ｍＭ）、ペニシリンＧ（１ ０ ０ Ｕ／ｍｇ） 、ス
トレプトマイシン（１００μｓ／ｄ）を加えた１０％牛
胎児血清含有ＲＰＭＩ１６４０培地０．２一中にて２日
間培養し、培養上浦中のＩＬ−２活性を次の方法で測定
した。Example 2 Effect on IL-2 production in lymphocyte mixed reaction 1) Test method B^LB/c mouse cells (5xlO') were used as responding cells and exposed to X-ray irradiation (3000 rad).
6 mouse tile cells (5 x 10') as stimulator cells, N-(2-phenylethyl)-3.6.6-}limethyl-5
．． 6-DihyP loimidazo(2,1-b]thiazole-2
- Carboxamide (test drug) and L-glutamine (2
IL-2 in cultured Kamiura was cultured for 2 days in RPMI 1640 medium 0.2 mm containing 10% fetal bovine serum supplemented with penicillin G (100 U/mg) and streptomycin (100 μs/d). Activity was measured by the following method.
２）ＩＬ−２活性測定法
得られた培養上清の２倍希釈系列を作威し、ＩＬ−２依
存性株ＣＴＬＬ （Ｊ， Ｂｘｐ．Ｍｅｄ，， １４９
， ２７３ 〜２７８ （１９７９）） （ ４ ｘ
１ ０ ’）に加えて２４時間培養した。培養終了６
時間前に０．２５μＣｉ ［ ６ −’Ｈ〕チミジンを
添加し、ＣＴＬＬ−２に取り込まれる放射活性を測定し
た。2) IL-2 activity measurement method A 2-fold dilution series of the obtained culture supernatant was prepared, and the IL-2-dependent strain CTLL (J, Bxp. Med, 149
, 273-278 (1979)) (4 x
10') and cultured for 24 hours. Cultivation completed 6
Before that time, 0.25 μCi [ 6 -'H]thymidine was added, and the radioactivity incorporated into CTLL-2 was measured.
３）測定結果
リンパ球混合反応２日目の培養上浦中のＩＬ−２活性（
各３例の平均値士標準誤差）を測定した結果は、
次の通りである。3) Measurement results IL-2 activity in cultured Kamiura on the second day of lymphocyte mixed reaction (
The results of measuring the average value (standard error) for each of the three cases are as follows.
上記の結果から、Ｎ− （２−フエニルエチル〉−３．
６．６−｝リメチル−５．６−ジヒドロイミダゾ〔２、
１−ｂ〕チアゾール−２−カルポキサミドは１０１〜１
０−’ＭにてＩＬ−２産生量を有意に増加させた。From the above results, N-(2-phenylethyl>-3.
6.6-}limethyl-5,6-dihydroimidazo[2,
1-b] Thiazole-2-carpoxamide is 101-1
IL-2 production was significantly increased at 0-'M.
本有効成分は優れたＩＬ−２産生促進活性を有し、これ
を含有する本発明！し−２産生促進剤は癌、細菌感染、
ウィルス性疾患、免疫不全症、自己免疫疾患などの治療
、予防剤として有用である。This active ingredient has excellent IL-2 production promoting activity, and the present invention contains this active ingredient! Shi-2 production promoters are effective against cancer, bacterial infection,
It is useful as a therapeutic or preventive agent for viral diseases, immunodeficiency diseases, autoimmune diseases, etc.
以 上that's all
Claims (1)
チル−５、６−ジヒドロイミダゾ〔２、１−ｂ〕チアゾ
ール−２−カルボキサミドまたはその非毒性塩を有効成
分として含有することを特徴とするインターロイキン−
２産生促進剤。[Claims] 1,N-(2-phenylethyl)-3,6,6-trimethyl-5,6-dihydroimidazo[2,1-b]thiazole-2-carboxamide or a non-toxic salt thereof Interleukin characterized by being contained as a component
2 production promoter.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1157327A JPH0324012A (en) | 1989-06-20 | 1989-06-20 | Production promoter for interleukin-2 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1157327A JPH0324012A (en) | 1989-06-20 | 1989-06-20 | Production promoter for interleukin-2 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0324012A true JPH0324012A (en) | 1991-02-01 |
Family
ID=15647274
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1157327A Pending JPH0324012A (en) | 1989-06-20 | 1989-06-20 | Production promoter for interleukin-2 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0324012A (en) |
-
1989
- 1989-06-20 JP JP1157327A patent/JPH0324012A/en active Pending
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