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公开(公告)号：US06579860B1
公开(公告)日：2003-06-17
申请号：US09623014
申请日：2000-09-27
申请人： Junzo Koike , Yuriko Funaba , Masahiko Tanahashi , Seiji Okazaki , Masatoshi Ito
发明人： Junzo Koike , Yuriko Funaba , Masahiko Tanahashi , Seiji Okazaki , Masatoshi Ito
IPC分类号： A61K31663
CPC分类号： A61K31/663 , A61K31/675
摘要： An interleukin-6 production inhibitor is provided containing a methanebisphosphonic acid derivative as an active component, which has inhibitory effects on interleukin-6 production and is useful in prevention and treatment of diseases due to abnormal production of the interleukin-6. This pharmaceutical is anticipated to have effects in prevention and treatment of diseases related to the interleukin-6, for example, thrombocytosis, inflammatory diseases, abnormal immune response diseases, osteoporosis, rheumatoid arthritis, hypercalcemia, multiple myeloma, cachexia, and nephritis.
摘要翻译： 提供了含有作为活性成分的甲烷二膦酸衍生物的白细胞介素-6产生抑制剂，其对白细胞介素-6产生具有抑制作用，并且可用于预防和治疗由于白细胞介素-6异常产生引起的疾病。 预期该药物可预防和治疗与白细胞介素-6相关的疾病，例如血小板增多症，炎性疾病，异常免疫应答疾病，骨质疏松症，类风湿性关节炎，高钙血症，多发性骨髓瘤，恶病质和肾炎。
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公开(公告)号：US06555529B1
公开(公告)日：2003-04-29
申请号：US09380090
申请日：1999-08-25
申请人： Yuriko Funaba , Junzo Koike , Masahiko Tanahashi , Seiji Okazaki , Masatoshi Ito
发明人： Yuriko Funaba , Junzo Koike , Masahiko Tanahashi , Seiji Okazaki , Masatoshi Ito
IPC分类号： A61K3166
CPC分类号： A61K31/66 , A61K31/663 , A61K31/675
摘要： The present invention has the objective of offering drug for treating abnormalities in bone marrow which corrects the biological balance in the bone marrow, in particular which has the effect of suppressing inflammatory cell infiltration and suppressing cell growth-differentiation factor increase. The present invention relates to drug for treating abnormalities in bone marrow which has, as an effective component, a methanebisphosphonic acid derivative, ester thereof, medicinally acceptable salt thereof, or a hydrate of these. The methanebisphosphonic acid derivatives of the present invention show an outstanding bone marrow abnormality therapeutic effect, so efficacy can be expected in the prevention and treatment of rheumatoid arthritis, multiple myeloma, osteomyelitis and other bone marrow abnormalities. Furthermore, application can also be expected in the prevention and treatment of hypoplastic anaemia, myelocytic leukaemia and other such haematopoietic disorders.
摘要翻译： 本发明的目的是提供一种用于治疗骨髓中异常的药物，其用于校正骨髓中的生物平衡，特别是其具有抑制炎性细胞浸润和抑制细胞生长分化因子增加的作用。本发明涉及 作为有效成分的甲烷二膦酸衍生物，其酯，药学上可接受的盐或其水合物的骨髓中异常的药物。本发明的甲烷二膦酸衍生物显示出优异的骨髓异常治疗效果 因此预防和治疗类风湿性关节炎，多发性骨髓瘤，骨髓炎等骨髓异常的疗效。 此外，还可以预期在预防和治疗发育不全的贫血，骨髓性白血病和其他这种造血障碍中的应用。
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公开(公告)号：US06692758B1
公开(公告)日：2004-02-17
申请号：US09806151
申请日：2001-03-28
申请人： Masatoshi Ito , Yuriko Kawai , Seiji Okazaki , Masahiko Tanahashi , Kang Jung Kim , Miho Iwase
发明人： Masatoshi Ito , Yuriko Kawai , Seiji Okazaki , Masahiko Tanahashi , Kang Jung Kim , Miho Iwase
IPC分类号： A61K31663
CPC分类号： A61K31/663 , A61L27/54 , A61L2300/216 , A61L2300/432 , C07F9/3839
摘要： The present invention relates to an implant attachment stabilizer having, as an effective component, a methanebisphosphonic acid derivative represented by general formula (I) [where, in the formula, X, Y, m, n, , A, B, R1, R2, R3 and R4 are as defined in the Specification], or hydrate thereof. The methanebisphosphonic acid derivatives represented by general formula (I) or the hydrates thereof, to which the present invention relates, have an interstitial tissue proliferation inhibiting action and an osteolytic factor production inhibiting action and, in particular, since they inhibit osteolysis through the inhibition of the interstitial tissue proliferation which accompanies implant attachment and the inhibition of osteolysis factor production at the implant periphery, they are effective in the prevention of implant loosening and detachment, and it is possible to extend the implant attachment period in the case of implants such as artificial joints, and implants in the oro-dental field.
摘要翻译： 本发明涉及具有通式（I）表示的甲烷二膦酸衍生物作为有效成分的植入物附着稳定剂[式中，X，Y，m，n，
，A，B，R 1，R 2，R 本发明涉及的通式（I）表示的甲烷二膦酸衍生物或其水合物具有间质组织增殖抑制作用 并且特别是由于它们通过抑制伴随植入物附着的间质组织增殖和抑制植入物周围的骨质疏松因子产生而抑制骨质溶解，因此它们有效地防止植入物松动和 脱离，它是可能的 e以在诸如人造关节的植入物和牙科领域中的植入物的情况下延长植入物固定周期。 -
4.发明授权
公开(公告)号：US5618804A
公开(公告)日：1997-04-08
申请号：US178320
申请日：1994-01-14
CPC分类号： C07F9/3865 , C07F9/386 , C07F9/4025
摘要： A methane diphosphonic acid derivative represented by the general formula (I): ##STR1## wherein, X and Y are defined in the specification; m represents an integer of 0 to 3; n represents an integer of 0 to 4; and each X of the (X).sub.m and each Y of the (Y).sub.n may be either identical or different; . . . represents a double bond or single bond; A is --(CH.sub.2)a--(D)b--(CH.sub.2)c-- (wherein D is sulfur, oxygen, NH, alkyl-substituted N, or CH.sub.2, a and c are integers of 0 to 10 and b is 0 or 1), or --(CH.dbd.CH)d.dbd.CH= (wherein d is an integer of 0 to 2, and B does not exist when A represents --CH.dbd.CH)d--CH.dbd.), B refers to a hydrogen atom, alkyl group, amino group, monoalkylamino group, dialkylamino group, acylamino group, hydroxyl group, alkoxy group, trialkylsiloxy group or acyloxy group, and each of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is hydrogen atom, straight or branched alkyl group having 1 to 7 carbon atoms, or pharmacologically allowed cation, and these may be identical or different, as described. The compounds of the present invention have excellent IL-1 inhibitory action, antioxidative action and bone resorption inhibitory action, and are useful as an antiinflammatory drug, antirheumatic drug, or autoimmune disease drug.
摘要翻译： PCT No.PCT / JP93 / 00014 Sec。 371日期1994年1月14日 102（e）日期1994年1月14日PCT提交1993年1月8日PCT公布。 第WO94 / 01442号公报 日本1994年1月20日由通式（I）表示的甲烷二膦酸衍生物：其中X和Y在说明书中定义; m表示0〜3的整数， n表示0〜4的整数， （X）m的每个X和（Y）n的每个Y可以相同或不同; + E，uns。 。 + EE表示双键或单键; A是 - （CH 2）a - （D）b - （CH 2）c - （其中D是硫，氧，NH，烷基取代的N或CH 2，a和c是0至10的整数，b是0或 1）或 - （CH = CH）d = CH =（其中d为0〜2的整数，当A表示-CH = CH时，B不存在）d-CH =），B表示氢原子 烷基，氨基，一烷基氨基，二烷基氨基，酰氨基，羟基，烷氧基，三烷基甲硅烷氧基或酰氧基，R 1，R 2，R 3和R 4各自为氢原子，具有1〜 7个碳原子或药理学上允许的阳离子，并且它们可以相同或不同，如所述。 本发明的化合物具有优异的IL-1抑制作用，抗氧化作用和骨吸收抑制作用，可用作抗炎药，抗风湿药物或自身免疫疾病药物。
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公开(公告)号：US5683992A
公开(公告)日：1997-11-04
申请号：US617937
申请日：1996-03-15
CPC分类号： C07F9/386 , C07F9/3865 , C07F9/4025 , C07F9/404 , C07F9/405
摘要： The present invention relates to a methanediphosphonate derivative, its manufacturing process, and pharmaceutical applications, that is represented with the following formula: ##STR1## wherein, D is either sulfur, oxygen, NH, alkyl-substituted N, CH.sub.2, or SCH.sub.2, X represents an alkyl group, alkyl group having a hetero atom as a substitution group, an aryl group or an acyl group, m represents an integer of 1 to 5, and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently represent hydrogen, alkyl groups having 1 to carbon atoms or pharmaceutically allowable cations. .function.The compounds of the present invention have excellent IL-1 inhibitory action, antioxidation action and bone resorption inhibitory action, and are useful as antiinflammatory agents, antirheumatic agents, bone metabolic disease drugs, autoimmune disease drugs, or osteoporosis drugs.
摘要翻译： 本发明涉及由下式表示的甲基二膦酸酯衍生物，其制备方法和药物应用：
或 取代的N，CH 2或SCH 2，X表示烷基，具有 杂原子作为取代基，芳基或酰基，m表示1〜5的整数，R 1，R 2，R 3和R 4分别表示氢，具有1〜碳原子的烷基或药学上可允许的阳离子。 f本发明的化合物具有优异的IL-1抑制作用，抗氧化作用和骨吸收抑制作用，可用作抗炎剂，抗风湿剂，骨代谢疾病药物，自身免疫性疾病药物或骨质疏松症药物。 -
6.发明授权Methanediphosphonate derivative, its manufacturing process and its pharmaceutical applications 失效甲烷二膦酸衍生物，其制造工艺及其制药应用
公开(公告)号：US5527940A
公开(公告)日：1996-06-18
申请号：US340819
申请日：1994-11-17
CPC分类号： C07F9/386 , C07F9/3865 , C07F9/4025 , C07F9/404 , C07F9/405
摘要： The present invention relates to a methanediphosphonate derivative, its manufacturing process and pharmaceutical applications, that is represented with the following formula: ##STR1## (wherein, B is either hydrogen, an alkyl group, hydroxyl group, alkoxy group or amino group, D is either sulfur, oxygen, NH, alkyl-substituted N, CH.sub.2 or SCH.sub.2, X represents an alkyl group, alkyl group having a hetero atom as a substitution group, an aryl group or an acyl group, m represents an integer of 1 to 5, and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently represent hydrogen, alkyl groups having 1 to 7 carbon atoms or pharmaceutically allowable cations). The compound of the present invention has excellent IL-1 inhibitory action, antioxidation action and bone resorption inhibitory action, and is useful as an antiinflammatory agent, antirheumatic, bone metabolic disease drug, autoimmune disease drug, osteoporosis drug and so forth.
摘要翻译： 本发明涉及由下式表示的甲基二膦酸酯衍生物，其制备方法和药物应用：其中，B为氢，烷基，羟基，烷氧基或氨基 ，D是硫，氧，NH，烷基取代的N，CH 2或SCH 2，X表示烷基，具有杂原子作为取代基的烷基，芳基或酰基，m表示1的整数 至5，R 1，R 2，R 3和R 4独立地表示氢，具有1至7个碳原子的烷基或药学上允许的阳离子）。 本发明化合物具有优异的IL-1抑制作用，抗氧化作用和骨吸收抑制作用，可用作抗炎剂，抗风湿剂，骨代谢疾病药物，自身免疫疾病药物，骨质疏松症药物等。
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