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1. 发明授权

US5795897A Oxohexyl methylxanthine compounds 失效
标题翻译：氧代己基甲基黄嘌呤化合物
公开(公告)号：US5795897A
公开(公告)日：1998-08-18
申请号：US227295
申请日：1994-04-13
申请人： Gail Underiner
发明人： Gail Underiner
IPC分类号： A61K31/522 , A61K31/52
CPC分类号： A61K31/522 , Y10S514/885 , Y10S514/886
摘要： There is disclosed a pharmaceutical composition comprising 1-(5-oxohexyl)-3-methylxanthine in admixture with a pharmaceutically acceptable excipient, wherein the pharmaceutical composition is useful for treating an immune disorder. There is also disclosed a method to modulate the response of a target cell to a stimulus, which method comprises contacting said cell with an amount of 1-(5-oxohexyl)-3-methylxanthine or a pharmaceutical composition thereof, wherein said amount effects a diminution in elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA in said cells wherein said elevated levels are stimulated by an agent capable of elevating levels of said PA and said DAG, said diminution being equal to or greater than the diminution effected by treating said cells with pentoxifylline (PTX) at a concentration of 0.5 mmol, thereby modulating the response of said target cell.
摘要翻译：公开了包含与药学上可接受的赋形剂混合的1-（5-氧代己基）-3-甲基黄嘌呤的药物组合物，其中该药物组合物可用于治疗免疫疾病。还公开了一种调节靶细胞对刺激的反应的方法，该方法包括使所述细胞与一定量的1-（5-氧代己基）-3-甲基黄嘌呤或其药物组合物接触，其中所述量对在所述细胞中源自所述PA的不饱和，非花生四烯酸磷脂酸（PA）和二酰基甘油（DAG）的升高水平的降低，其中所述升高的水平由能够提高所述PA和所述DAG水平的药剂刺激，所述减少为等于或大于以0.5mmol浓度的己酮可可碱（PTX）处理所述细胞所产生的减少，从而调节所述靶细胞的反应。

2. 发明授权

US5777115A Acetal-and ketal-substituted pyrimidine compounds 失效
标题翻译：乙缩醛和缩酮取代的嘧啶化合物
公开(公告)号：US5777115A
公开(公告)日：1998-07-07
申请号：US193331
申请日：1994-02-07
申请人： Alistair Leigh , Gail Underiner
发明人： Alistair Leigh , Gail Underiner
IPC分类号： C07D473/20 , C07D239/26 , A61K31/505
CPC分类号： C07D473/20
摘要： Acetal-and ketal-substituted compounds and pharmaceutical compositions thereof have the following formula: CORE MOIETY--(R).sub.j, including resolved enantiomers and/or diastereomers, hydrates, salts, solvates and mixtures thereof. j is an integer from one to three, the core moiety is non-cyclic or cyclic a monocyclic moiety having at least one nitrogen atom within the ring and R may be selected from among hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted alkyl C.sub.(1-6), alkenyl C.sub.(2-6), cyclic or heterocyclic groups, and groups having a structure prescribed by formula I. At least one R has the formula I: --(CH.sub.2).sub.n --C--(R.sub.1).sub.3 I wherein n is an integer from three to twenty; R.sub.1 is selected from among hydrogen; halogen; hydroxide; substituted or unsubstituted C.sub.(1-6) alkyl, C.sub.(1-6) alkoxy, C.sub.2-6) alkenyl, cyclic or heterocyclic group; --OR.sub.2, R.sub.2 being hydrogen or a substituted or unsubstituted C.sub.(1-6) alkyl, C.sub.(2-6) alkenyl, cyclic or heterocyclic group; --(CH.sub.2).sub.p --C(R.sub.3).sub.3 (wherein p is zero or an integer from one to ten, R.sub.3 is hydrogen, halogen, hydroxide, substituted or unsubstituted C.sub.(1-6) alkyl, C.sub.(1-6) alkoxy, C.sub.(2-6) alkenyl, cyclic or heterocyclic group, or --OR.sub.2, R.sub.2 being defined above). The inventive compounds are useful in a large variety of therapeutic indications for treating or preventing disease mediated by intracellular signaling through specific intracellular signaling pathways.
摘要翻译：乙缩醛和缩酮取代的化合物及其药物组合物具有下式：CORE MOIETY-（R）j，包括拆分的对映体和/或非对映异构体，水合物，盐，溶剂合物及其混合物。 j是1至3的整数，核心部分是非环状或环状的在环内具有至少一个氮原子的单环部分，R可以选自氢，卤素，羟基，氨基，取代或未取代的烷基C （1-6），烯基C（2-6），环状或杂环基，以及具有式I规定结构的基团。至少一个R具有式I： - （CH 2）n C-（R 1）3 I其中 n是三至二十的整数; R1选自氢; 卤素; 氢氧化物; 取代或未取代的C（1-6）烷基，C（1-6）烷氧基，C 2-6）烯基，环状或杂环基; -OR2，R2是氢或取代或未取代的C（1-6）烷基，C（2-6）烯基，环状或杂环基; - （CH 2）p C（R 3）3（其中p为0或1至10的整数，R 3为氢，卤素，氢氧根，取代或未取代的C 1-6烷基，C（1-6）烷氧基，C （2-6）烯基，环状或杂环基，或-OR2，R2定义如上）。本发明化合物可用于治疗或预防通过特定细胞内信号传导途径的细胞内信号传导介导的疾病的各种治疗适应症。

3. 发明授权

US5866576A Epoxide-containing compounds 失效
标题翻译：含环氧化物的化合物
公开(公告)号：US5866576A
公开(公告)日：1999-02-02
申请号：US778563
申请日：1997-01-03
申请人： Gail Underiner , J. Peter Klein , John Michnick , Alistair Leigh , Anil Kumar
发明人： Gail Underiner , J. Peter Klein , John Michnick , Alistair Leigh , Anil Kumar
IPC分类号： C07D303/36 , C07D405/06 , C07D473/10 , A61K31/505 , C07D239/02
CPC分类号： C07D405/06 , C07D303/36 , C07D473/10
摘要： Disclosed are enantiomers, diastereomers, salts, solvates, hydrates and mixtures thereof, of formula I: ##STR1## The core moiety is a monocyclic ring structure having five to six ring atoms and two nitrogen atoms at the 1 and 3 positions, n is an integer from 4 to 16, R.sub.1 and R.sub.2 are hydrogen, halogen or C.sub.1-12 alkyl or alkenyl, and (CH.sub.2).sub.n may be optionally substituted by a hydroxyl, halogen, oxygen, a C.sub.1-4 alkyl group or a dimethylamino group. The compounds and pharmaceutical composition thereof are useful in methods for treating an individual having a disease or treatment-induced toxicity mediated through a second messenger.
摘要翻译：公开了式I的对映异构体，非对映异构体，盐，溶剂化物，水合物及其混合物：核心部分是在1和3位具有5至6个环原子和2个氮原子的单环环结构，n为 4至16的整数，R 1和R 2是氢，卤素或C 1-12烷基或链烯基，和（CH 2）n可任选被羟基，卤素，氧，C 1-4烷基或二甲基氨基取代。化合物及其药物组合物可用于治疗患有通过第二信使介导的疾病或治疗诱导的毒性的个体的方法。

4. 发明授权

US5521315A Olefin substituted long chain compounds 失效
标题翻译：烯烃取代的长链化合物
公开(公告)号：US5521315A
公开(公告)日：1996-05-28
申请号：US59697
申请日：1993-05-10
申请人： Gail Underiner , David Porubek , J. Peter Klein , Elisa Eiseman , Alistair Leigh , Anil Kumar , John Michnick
发明人： Gail Underiner , David Porubek , J. Peter Klein , Elisa Eiseman , Alistair Leigh , Anil Kumar , John Michnick
IPC分类号： C07D239/54 , A61K31/015 , A61K31/047 , A61K31/195 , A61K31/40 , A61K31/403 , A61K31/4035 , A61K31/505 , A61K31/52 , A61K31/522 , A61P1/00 , A61P1/02 , A61P1/16 , A61P3/00 , A61P3/08 , A61P3/10 , A61P11/00 , A61P13/02 , A61P15/00 , A61P19/10 , A61P25/28 , A61P29/00 , A61P37/00 , A61P43/00 , C07C13/08 , C07C13/16 , C07C15/40 , C07C49/20 , C07C49/647 , C07D209/48 , C07D473/06 , C07D211/88 , C07D239/80
CPC分类号： C07D473/06
摘要： There is disclosed an olefin-substituted compound having the formula:R--(core moiety),wherein R is a straignt chain hydrocarbon having at least one double bond and a carbon chain length of from about 6 to about 18 carbon atoms, wherein multiple double bonds are separated from each other by at least three carbon atoms, wherein the closest double bond to the core moiety is at least five carbon atoms from the core moiety, and wherein the hydrocarbon chain may be substituted by a hydroxyl, halo, keto or dimethylanimo group and/or interrupted by an oxygen atom and salts thereof and pharmaceutical compositions thereof.
摘要翻译：公开了具有下式的烯烃取代的化合物：R-（核心部分），其中R是具有至少一个双键且碳链长度为约6至约18个碳原子的直链烃，其中多个双键彼此分开至少三个碳原子，其中与核心部分最接近的双键是至少五个来自核心部分的碳原子，并且其中烃链可以被羟基，卤素，酮基或二甲基亚胺基取代组和/或被氧原子及其盐和其药物组合物中断。

5. 发明授权

US6020337A Electronegative-substituted long chain xanthine compounds 失效
标题翻译：电负性取代长链黄嘌呤化合物
公开(公告)号：US6020337A
公开(公告)日：2000-02-01
申请号：US950810
申请日：1997-09-16
申请人： Alistair J. Leigh , John Michnick , Anil M. Kumar , J. Peter Klein , Gail Underiner
发明人： Alistair J. Leigh , John Michnick , Anil M. Kumar , J. Peter Klein , Gail Underiner
IPC分类号： C07D209/48 , C07D239/54 , C07D239/96 , C07D473/10 , A61K31/52 , C07D473/00
CPC分类号： C07D209/48 , C07D239/54 , C07D239/96 , C07D473/10
摘要： Therapeutic compounds, including resolved enantiomers and/or diastereomers, hydrates, salts, solvates and mixtures thereof, having a formula: ##STR1## wherein R.sub.0 is selected from the group consisting of hydrogen, halo, hydroxyl, amino, substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(2-10) alkenyl, cyclic or heterocyclic groups, wherein the substituents of substituted C.sub.(1-10) alkyl, C.sub.(2-10) alkenyl are other than halo; n is an integer from one to sixteen; R.sub.1, R.sub.2, and R.sub.3 are independently selected from the group consisting of a halo; haloacetoxy; hydrogen; hydroxy; oxo; --N.dbd.C.dbd.S; --N.dbd.C.dbd.O; --0--C.tbd.N; --C.tbd.N; --N.dbd.N.dbd.N; and --C--(R.sub.5).sub.3, R.sub.5 being independently a halo or hydrogen, at least one R.sub.5 being halo, at least one of R.sub.1, R.sub.2, and R.sub.3 being halo, cyano, isocyano, isothiocyano, azide or haloacetoxy group; R.sub.4 is hydrogen, C.sub.(1-6) alkyl, C.sub.(1-6) alkenyl, cyclo C.sub.(4-6) alkyl, or phenyl; one or more hydrogen atoms of (CH.sub.2).sub.n --CH.sub.a --CH.sub.b --CH.sub.c may be replaced with: i) at least one of halogen atom, hydroxyl, oxo, substituted or unsubstituted C.sub.(1-10) alkyl, C.sub.(1-10) alkoxyalkyl, or C.sub.(2-10) alkenyl; or ii) one or more unsaturated bonds; and any two adjacent carbon atoms of (CH.sub.2).sub.n --CH.sub.a --CH.sub.b --CH.sub.c may be instead separated by at least one oxygen atom. These compounds are useful in treating or preventing diseases by inhibiting selective second messenger pathways.
摘要翻译：具有下式的治疗化合物，包括拆分的对映异构体和/或非对映异构体，水合物，盐，溶剂合物及其混合物，其中R 0选自氢，卤素，羟基，氨基，取代或未取代的C（1-10）烷基，C（2-10）烯基，环状或杂环基团，其中取代的C（1-10）烷基，C（2-10）烯基的取代基不是卤素; n是从1到16的整数; R 1，R 2和R 3独立地选自卤素; 卤代乙酰氧基; 氢; 羟基; 氧代 -N = C = S; -N = C = O; -0-C 3BOND N; -C 3BOND N; -N = N = N; 和 - （R 5）3，R 5独立地为卤素或氢，至少一个R 5为卤素，R 1，R 2和R 3中的至少一个为卤素，氰基，异氰基，异硫氰基，叠氮基或卤代乙酰氧基; R4是氢，C（1-6）烷基，C（1-6）烯基，环C（4-6）烷基或苯基; （CH 2）n -CH-CHB-CHc的一个或多个氢原子可以被：i）卤素原子，羟基，氧代，取代或未取代的C（1-10）烷基，C（1-10 ）烷氧基烷基或C（2-10）烯基; 或ii）一个或多个不饱和键; 并且（CH 2）n -CH CH-CH c CH 2的任何两个相邻的碳原子可以被至少一个氧原子隔开。这些化合物可用于通过抑制选择性第二信使途径来治疗或预防疾病。

6. 发明申请

US20090247754A1 METHOD OF PREPARING HUPERZINE A AND DERIVATIVES THEREOF 审中-公开
标题翻译：制备胡哌嗪A及其衍生物的方法
公开(公告)号：US20090247754A1
公开(公告)日：2009-10-01
申请号：US12411111
申请日：2009-03-25
申请人： Gail Underiner , Frank Gibson , Linli He , Harihara Subramanian Meera , Jesudoss Mercy Gnanadeepam , Ramanathan Saiganesh , Stephen R. Tudhope , Manouchehr Azadi-Ardakani
发明人： Gail Underiner , Frank Gibson , Linli He , Harihara Subramanian Meera , Jesudoss Mercy Gnanadeepam , Ramanathan Saiganesh , Stephen R. Tudhope , Manouchehr Azadi-Ardakani
IPC分类号： C07D221/22 , C07D215/00
CPC分类号： C07D221/22 , C07D215/22 , C07D215/48
摘要： The present invention is related to the synthesis of huperzine A. The synthesis includes a variety of process steps that increase productivity, reduce safety concerns, and allow for increasing production of compounds of desired optical isomer. The inventive methods may encompass a single improved reaction step that may be incorporated into a known reaction process for synthesizing huperzine A or a derivative thereof to improve the overall reaction. The inventive methods also encompass complete synthesis methods for preparing huperzine A or a derivative thereof.
摘要翻译：本发明涉及石杉碱甲的合成。合成包括提高生产率，减少安全性问题并允许增加所需旋光异构体化合物生产的各种方法步骤。本发明的方法可以包括单个改进的反应步骤，其可以并入用于合成石杉碱甲或其衍生物以改善总体反应的已知反应方法中。本发明的方法还包括制备石杉碱甲或其衍生物的完整合成方法。

7. 发明授权

US5473070A Substituted long chain alcohol xanthine compounds 失效
标题翻译：取代长链醇黄嘌呤化合物
公开(公告)号：US5473070A
公开(公告)日：1995-12-05
申请号：US976353
申请日：1992-11-16
申请人： Gail Underiner , David Porubek , J. Peter Klein , Paul Woodson
发明人： Gail Underiner , David Porubek , J. Peter Klein , Paul Woodson
IPC分类号： A61K31/519 , C07C233/91 , C07C317/18 , C07D209/48 , C07D211/76 , C07D211/88 , C07D215/22 , C07D239/54 , C07D239/88 , C07D239/96 , C07D295/088 , C07D473/06 , C07D473/08 , C07D473/10 , C07D475/02 , C07D473/04 , A61K31/52
CPC分类号： C07D209/48 , A61K31/519 , C07C233/91 , C07C317/18 , C07D211/76 , C07D211/88 , C07D215/22 , C07D239/54 , C07D239/88 , C07D239/96 , C07D295/088 , C07D473/06 , C07D473/08 , C07D473/10 , C07D475/02
摘要： There is disclosed compounds and pharmaceutical compositions comprising compounds of the formula: ##STR1## wherein each of one or two R is independently ##STR2## wherein n is an integer from 7 to 20, at least one of X or Y is --OH and if one of X or Y is --OH then the other X or Y is H, CH.sub.3, CH.sub.3 --CH.sub.2, CH.sub.3 --(CH.sub.2).sub.2 --, or (CH.sub.3).sub.2 --CH.sub.2 --, and W.sub.1, W.sub.2, and W.sub.3 is independently H, CH.sub.3, CH.sub.3 --CH.sub.2, CH.sub.3 --(CH.sub.2).sub.2 --, or (CH.sub.3).sub.2 --CH.sub.2 --, and wherein the alkyl groups may be substituted by a hydroxyl, halo or dimethylamino group and/or interrupted by an oxygen atom, H or alkyl (1-4C), including resolved enantiomers and/or diastereomers, salts and mixtures thereof. In particular, the compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with said cells. The modulatory effect depends on the nature of the target cell and the stimulus applied.
摘要翻译：公开了包含下式化合物的化合物和药物组合物：独立地为：其中n为7至20的整数，X或Y中的至少一个为-OH，如果X或Y中的一个为-OH，则其它X或Y是H，CH 3，CH 3 -CH 2，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - ，W 1，W 2和W 3独立地为H，CH 3，CH 3 -CH 2， CH 2）2 - 或（CH 3）2 -CH 2 - ，并且其中烷基可以被羟基，卤素或二甲基氨基取代和/或被氧原子H或烷基（1-4C）中断，包括拆分的对映异构体和/或非对映体，其盐和混合物。特别地，所述化合物在主刺激的几秒钟内与所述细胞的接触降低了源自所述PA的不饱和，非花生四烯酸磷脂酸（PA）和二酰基甘油（DAG）的升高水平。调节作用取决于靶细胞的性质和应用的刺激。

8. 发明授权

US5354756A Olefin-substituted long chain xanthine compounds 失效
标题翻译：烯烃取代的长链黄嘌呤化合物
公开(公告)号：US5354756A
公开(公告)日：1994-10-11
申请号：US3372
申请日：1993-01-12
申请人： Gail Underiner , David Porubek , J. Peter Klein
发明人： Gail Underiner , David Porubek , J. Peter Klein
IPC分类号： C07D473/06 , A61K31/52 , C07D473/02
CPC分类号： C07D473/06
摘要： There is disclosed compounds and pharmaceutical compositions having a xanthine core and one or two hydrocarbon side chains bonded to a ring nitrogen atom, wherein the hydrocarbon side chains are independently a straight chain hydrocarbon having at least one double bond in a carbon chain length of from about 4 to about 18 carbon atoms in length, wherein multiple double bonds are separated from each other by at least three carbon atoms, and wherein the hydrocarbon chain may be substituted by a hydroxyl, halo or dimethylamino group and/or interrupted by an oxygen atom. The compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with cells. The modulatory effect depends on the nature of the target cell and the stimulus applied.
摘要翻译：公开了具有与环氮原子键合的黄嘌呤核和一个或两个烃侧链的化合物和药物组合物，其中烃侧链独立地为具有至少一个双键的碳链长度为约 4至约18个碳原子，其中多个双键彼此分开至少三个碳原子，并且其中烃链可以被羟基，卤素或二甲基氨基取代和/或被氧原子中断。该化合物在主要刺激的几秒钟内和与细胞接触的情况下，降低了源自所述PA的不饱和，非花生四烯酸磷脂酸（PA）和二酰基甘油（DAG）的升高水平。调节作用取决于靶细胞的性质和应用的刺激。

9. 发明授权

US5340813A Substituted aminoalkyl xanthine compounds 失效
标题翻译：取代的氨基烷基黄嘌呤化合物
公开(公告)号：US5340813A
公开(公告)日：1994-08-23
申请号：US973804
申请日：1992-11-09
申请人： J. Peter Klein , Gail Underiner , Alistair Leigh
发明人： J. Peter Klein , Gail Underiner , Alistair Leigh
IPC分类号： C07D251/00 , A61K31/44 , A61K31/4402 , A61K31/505 , A61K31/517 , A61K31/52 , A61K31/522 , A61P1/00 , A61P1/16 , A61P3/00 , A61P7/00 , A61P9/00 , A61P13/02 , A61P15/00 , A61P17/00 , A61P31/00 , A61P37/00 , A61P43/00 , C07D213/64 , C07D239/54 , C07D239/62 , C07D239/72 , C07D471/02 , C07D473/04 , C07D473/06 , C07D473/08 , C07D473/10 , C07D473/30
CPC分类号： A61K31/522 , A61K31/52 , C07D473/04
摘要： Compounds of the formula ##STR1## wherein each of one or two R is independently ##STR2## wherein n is an integer from 4 to 18, each R.sub.1 ' and R.sub.2 ' is independently H, alkyl (1-4C) or alkenyl (1-4C); and R.sub.3 ' and R.sub.4 ' are independently H or CH.sub.3 ; and wherein the alkyl or alkenyl may be substituted by a hydroxyl, halo or dimethylamino group and/or interrupted by an oxygen atom, H or alkyl (1-4C), including resolved enantiomers and/or diastereomers and mixtures thereof. Preferably, n is from 6 to 10, R.sub.1 ' and R.sub.2 ' are independently H or methyl and R.sub.3 ' and R.sub.4 ' are H. In particular, the compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with said cells. The modulatory effect depends on the nature of the target cell and the stimulus applied.
摘要翻译：式1的化合物，其中一个或两个R各自独立地为其中n为4至18的整数，每个R 1'和R 2'独立地为H，烷基（1-4C）或链烯基（ 1-4C）; 且R 3'和R 4'独立地为H或CH 3; 并且其中所述烷基或链烯基可以被羟基，卤素或二甲基氨基取代和/或被氧原子H或烷基（1-4C）中断，包括拆分的对映异构体和/或非对映异构体及其混合物。优选地，n为6至10，R 1'和R 2'独立地为H或甲基，且R 3'和R 4'为H.特别地，该化合物降低不饱和，非花生四烯酸酯磷脂酸（PA）和二酰基甘油 DAG），其在主刺激的几秒钟内从所述PA衍生并与所述细胞接触。调节作用取决于靶细胞的性质和应用的刺激。

10. 发明授权

US6121270A Epoxide-containing compounds 失效
标题翻译：含环氧化物的化合物
公开(公告)号：US6121270A
公开(公告)日：2000-09-19
申请号：US98473
申请日：1998-06-17
申请人： Gail Underiner , J. Peter Klein , John Michnick , Alistair Leigh , Anil Kumar
发明人： Gail Underiner , J. Peter Klein , John Michnick , Alistair Leigh , Anil Kumar
IPC分类号： C07D303/36 , C07D405/06 , C07D473/10 , A61K31/52 , C07D473/04
CPC分类号： C07D405/06 , C07D303/36 , C07D473/10
摘要： Disclosed are enantiomers diastereomers, salts, solvates, hydrates and mixtures thereof, of formula I: ##STR1## The core moiety is non-cyclic or at least one five- to seven-membered ring, n is an integer from about 4 to about 16, R.sub.1 and R.sub.2 are hydrogen, halogen or C.sub.1-12 alkyl or alkenyl, and (CH.sub.2).sub.n may be substituted by a hydroxyl, halogen, oxygen, a (C.sub.1-4) alkyl group or a dimethylamino group. The compounds and pharmaceutical composition thereof are useful in methods for treating an individual having a disease or treatment-induced toxicity, mediated by second messenger activity.
摘要翻译：公开了式I的对映体非对映异构体，盐，溶剂合物，水合物及其混合物：核心部分是非环状或至少一个五至七元环，n是约4至约16的整数，R 1和 R2是氢，卤素或C1-12烷基或烯基，（CH2）n可以被羟基，卤素，氧，（C1-4）烷基或二甲氨基取代。所述化合物及其药物组合物可用于治疗由第二信使活性介导的具有疾病或治疗诱导的毒性的个体的方法。

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