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41. 发明授权

US08623867B2 Cyclic amine BACE-1 inhibitors having a benzamide substituent 有权
标题翻译：具有苯甲酰胺取代基的环胺BACE-1抑制剂
公开(公告)号：US08623867B2
公开(公告)日：2014-01-07
申请号：US13610162
申请日：2012-09-11
申请人： Jared N. Cumming , Ulrich Iserloh , Andrew Stamford , Corey Strickland , Johannes H. Voight , Yusheng Wu , Ying Huang , Yan Xia , Samuel Chackalamannil , Tao Guo , Douglas W. Hobbs , Thuy X. H. Le , Jeffrey H. Lowrie , Kurt W. Saionz , Suresh D. Babu
发明人： Jared N. Cumming , Ulrich Iserloh , Andrew Stamford , Corey Strickland , Johannes H. Voight , Yusheng Wu , Ying Huang , Yan Xia , Samuel Chackalamannil , Tao Guo , Douglas W. Hobbs , Thuy X. H. Le , Jeffrey H. Lowrie , Kurt W. Saionz , Suresh D. Babu
IPC分类号： A61K31/445 , A61K31/4458 , A61K31/454 , A61K31/4545 , A61K31/5377 , C07D295/027 , C07D401/06 , C07D401/12 , C07D413/12
CPC分类号： C07D243/08 , C07D205/04 , C07D207/08 , C07D207/09 , C07D207/12 , C07D207/26 , C07D209/52 , C07D211/26 , C07D211/46 , C07D217/18 , C07D233/32 , C07D241/04 , C07D241/08 , C07D401/06 , C07D401/10 , C07D401/12 , C07D403/12 , C07D403/14 , C07D409/06 , C07D409/12 , C07D413/06
摘要： Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is R is —C(O)—N(R27)(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I.Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease.Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.
摘要翻译：公开了下式的化合物或其药学上可接受的盐或溶剂化物，其中R1是R是-C（O）-N（R27）（R28），或其余的变量如说明书中所定义。还公开了包含式I化合物的药物组合物。还公开了治疗认知或神经变性疾病如阿尔茨海默病的方法。还公开了治疗认知或神经变性疾病的药物组合物和方法，其包含式I化合物与除式I以外的β-分泌酶抑制剂，HMG-CoA还原酶抑制剂，γ-分泌酶抑制剂，甾族抗炎剂，N-甲基-D-天冬氨酸受体拮抗剂，胆碱酯酶抑制剂或抗淀粉样蛋白抗体。

42. 发明申请

US20070270439A1 THROMBIN RECEPTOR ANTAGONISTS 审中-公开
标题翻译：硫蛋白受体拮抗剂
公开(公告)号：US20070270439A1
公开(公告)日：2007-11-22
申请号：US11774358
申请日：2007-07-06
申请人： Samuel Chackalamannil , Martin Clasby , William Greenlee , Yuguang Wang , Yan Xia , Enrico Veltri , Mariappan Chelliah
发明人： Samuel Chackalamannil , Martin Clasby , William Greenlee , Yuguang Wang , Yan Xia , Enrico Veltri , Mariappan Chelliah
IPC分类号： A61K31/4427 , A61K31/506 , A61P29/00 , A61P35/00 , A61P9/00 , A61P9/02 , A61P9/06 , A61P9/10 , A61P9/12 , C07D221/00 , C07D239/26
CPC分类号： C07D405/06 , C07D405/14 , C07D417/14
摘要： Heterocyclic-substituted tricyclics of the formula or a pharmaceutically acceptable salt thereof, wherein: the dotted line represents an optional single bond; represents an optional double bond; n is 0-2; Q is cycloalkyl, optionally substituted by R13 and R14; R13 and R14 are independently selected from (C1-C6)alkyl, (C3-C8)cycloalkyl, —OH, (C1-C6)alkoxy, R27-aryl(C1-C6)alkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halogen and haloalkyl; or R13 and R14 together form a spirocyclic or a heterospirocyclic ring of 3-6 atoms; Het is a mono- or bi-cyclic optionally substituted heteroaryl group; and B is a bond, alkylene, or optionally substituted alkenylene or alkynylene, wherein the remaining substituents are as defined in the specification, are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds. Combination therapy with other cardiovascular agents is also claimed.
摘要翻译：具有下式的杂环取代的三环或其药学上可接受的盐，其中：虚线表示任选的单键; “img id =”custom-character-00001“he =”2.79mm“wi =”7.03mm“file =”US20070270439A1-20071122-P00002.TIF“img-content =”character“img-format =”tif“/> 表示可选的双键; n为0-2; Q是环烷基，任选被R 13和R 14取代; R 13和R 14独立地选自（C 1 -C 6 -C 6）烷基，（C

43. 发明申请

US20060079684A1 Thrombin receptor antagonists 有权
标题翻译：凝血酶受体拮抗剂
公开(公告)号：US20060079684A1
公开(公告)日：2006-04-13
申请号：US11243708
申请日：2005-10-05
申请人： Samuel Chackalamannil , Mariappan Chelliah , Yan Xia , Keith Eagen
发明人： Samuel Chackalamannil , Mariappan Chelliah , Yan Xia , Keith Eagen
IPC分类号： C07D413/02 , C07D405/02
CPC分类号： C07D405/06 , C07D405/14 , C07D409/14 , C07D413/14 , C07D491/10
摘要： Heterocyclic-substituted tricyclics of the formula or a pharmaceutically acceptable salt or solvate of said compound, isomer or racemic mixture wherein represents an optional double bond, the dotted line is optionally a bond or no bond, resulting in a double bond or a single bond, as permitted by the valency requirement and wherein A, B, G, M, X, J, n, Het, R3, R10, R11, R32 and R33 are herein defined and the remaining substituents are as defined in the specification, are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds. Combination therapy with other cardiovascular agents is also claimed.
摘要翻译：式中的杂环取代三环或所述化合物，异构体或外消旋混合物的药学上可接受的盐或溶剂化物，其中表示可选的双键，虚线是可选的键或无键，导致双重键或单键，如价格要求所允许的，并且其中A，B，G，M，X，J，n，Het，R 3，R 10，本文定义了R 11，R 32和R 33，并且其余的取代基如说明书中所定义，以及药物含有它们的组合物和通过施用所述化合物治疗与血栓形成，动脉粥样硬化，再狭窄，高血压，心绞痛，心律失常，心力衰竭和癌症相关的疾病的方法。还要求与其它心血管药物联合治疗。

44. 发明申请

US20130004518A1 CYCLIC AMINE BACE-1 INHIBITORS HAVING A BENZAMIDE SUBSTITUENT 有权
标题翻译：具有苯甲酸替代物的循环胺BACE-1抑制剂
公开(公告)号：US20130004518A1
公开(公告)日：2013-01-03
申请号：US13610162
申请日：2012-09-11
申请人： Jared N. Cumming , Ulrich Iserloh , Andrew Stamford , Corey Strickland , Johannes H. Voight , Yusheng Wu , Ying Huang , Yan Xia , Samuel Chackalamannil , Tao Guo , Douglas W. Hobbs , Thuy X.H. Le , Jeffrey F. Lowrie , Kurt W. Saionz , Suresh D. Babu
发明人： Jared N. Cumming , Ulrich Iserloh , Andrew Stamford , Corey Strickland , Johannes H. Voight , Yusheng Wu , Ying Huang , Yan Xia , Samuel Chackalamannil , Tao Guo , Douglas W. Hobbs , Thuy X.H. Le , Jeffrey F. Lowrie , Kurt W. Saionz , Suresh D. Babu
IPC分类号： C07D207/09 , C07F9/572 , A61K31/675 , C07D217/18 , A61K31/472 , C07F9/62 , C07D207/12 , A61K31/4025 , C07D401/14 , A61K31/4439 , C07D205/04 , A61K31/397 , C07D211/26 , A61K31/4458 , C07D211/46 , A61K31/445 , C07D413/12 , A61K31/5377 , C07D401/12 , A61K31/454 , C07D401/04 , A61K31/451 , A61K31/4545 , C07D241/08 , A61K31/495 , C07D403/12 , A61K31/496 , C07D241/24 , C07D413/06 , C07D243/08 , A61K31/551 , A61K39/395 , A61K31/5415 , A61K31/505 , A61P25/00 , A61P25/28 , A61P29/00 , A61K31/40
CPC分类号： C07D243/08 , C07D205/04 , C07D207/08 , C07D207/09 , C07D207/12 , C07D207/26 , C07D209/52 , C07D211/26 , C07D211/46 , C07D217/18 , C07D233/32 , C07D241/04 , C07D241/08 , C07D401/06 , C07D401/10 , C07D401/12 , C07D403/12 , C07D403/14 , C07D409/06 , C07D409/12 , C07D413/06
摘要： Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, whereinR1 is R is —C(O)—N(R27)(R28) or and the remaining variables are as defined in the specification.Also disclosed are pharmaceutical compositions comprising the compounds of formula I.Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease.Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.
摘要翻译：公开了下式的化合物或其药学上可接受的盐或溶剂化物，其中R1是R是-C（O）-N（R27）（R28），或其余的变量如说明书中所定义。还公开了包含式I化合物的药物组合物。还公开了治疗认知或神经变性疾病如阿尔茨海默病的方法。还公开了治疗认知或神经变性疾病的药物组合物和方法，其包含式I化合物与除式I以外的分泌抑制剂抑制剂，HMG-CoA还原酶抑制剂，γ-分泌酶抑制剂，非 - 甾族抗炎药，N-甲基-D-天冬氨酸受体拮抗剂，胆碱酯酶抑制剂或抗淀粉样蛋白抗体。

45. 发明授权

US08003803B2 Fused ring thrombin receptor antagonists 有权
标题翻译：融合环凝血酶受体拮抗剂
公开(公告)号：US08003803B2
公开(公告)日：2011-08-23
申请号：US11734057
申请日：2007-04-11
申请人： Yan Xia , Samuel Chackalamannil
发明人： Yan Xia , Samuel Chackalamannil
IPC分类号： C07D263/00 , C07D413/00
CPC分类号： C07D405/06 , C07D498/04
摘要： Fused-ring, heterocyclic-substituted tricyclics of the formula or a pharmaceutically acceptable salt or solvate of said compound, isomer or racemic mixture wherein represents an optional double bond, and wherein An, En, Mn, Gn, Jn, R3, n7, R8, R9, R10, R11, R32, R33, X, Y, B and Het are herein defined and the remaining substituents are as defined in the specification, are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds. Combination therapy with other cardiovascular agents is also claimed.
摘要翻译：具有下式的稠环，杂环取代的三环或所述化合物的药学上可接受的盐或溶剂合物，异构体或外消旋混合物，其中表示任选的双键，并且其中An，En，Mn，Gn，Jn，R 3，n 7，R 8 本文定义了R9，R10，R11，R32，R33，X，Y，B和Het，其余取代基如说明书中所定义，以及含有它们的药物组合物以及治疗与血栓形成，动脉粥样硬化，再狭窄，高血压，心绞痛，心律失常，心力衰竭和癌症。还要求与其它心血管药物联合治疗。

46. 发明授权

US07662816B2 Cyclic amine BACE-1 inhibitors having a benzamide substituent 有权
标题翻译：具有苯甲酰胺取代基的环胺BACE-1抑制剂
公开(公告)号：US07662816B2
公开(公告)日：2010-02-16
申请号：US10910987
申请日：2004-08-04
申请人： Jared N. Cumming , Ulrich Iserloh , Andrew Stamford , Corey Strickland , Johannes H. Voigt , Yusheng Wu , Ying Huang , Yan Xia , Samuel Chackalamannil , Tao Guo , Douglas W. Hobbs , Thuy X. H. Le , Jeffrey F. Lowrie , Kurt W. Saionz , Suresh D. Babu
发明人： Jared N. Cumming , Ulrich Iserloh , Andrew Stamford , Corey Strickland , Johannes H. Voigt , Yusheng Wu , Ying Huang , Yan Xia , Samuel Chackalamannil , Tao Guo , Douglas W. Hobbs , Thuy X. H. Le , Jeffrey F. Lowrie , Kurt W. Saionz , Suresh D. Babu
IPC分类号： A61K31/496 , C07D401/12 , C07D401/14 , C07D403/12 , C07D409/12 , C07D211/34 , C07D207/16 , C07D207/26 , C07D243/08 , C07D413/12
CPC分类号： C07D243/08 , C07D205/04 , C07D207/08 , C07D207/09 , C07D207/12 , C07D207/26 , C07D209/52 , C07D211/26 , C07D211/46 , C07D217/18 , C07D233/32 , C07D241/04 , C07D241/08 , C07D401/06 , C07D401/10 , C07D401/12 , C07D403/12 , C07D403/14 , C07D409/06 , C07D409/12 , C07D413/06
摘要： Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is R is —C(O)—N(R27)(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I.Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease.Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.
摘要翻译：公开了下式的化合物或其药学上可接受的盐或溶剂化物，其中R1是R是-C（O）-N（R27）（R28），或其余的变量如说明书中所定义。还公开了包含式I化合物的药物组合物。还公开了治疗认知或神经变性疾病如阿尔茨海默病的方法。还公开了治疗认知或神经变性疾病的药物组合物和方法，其包含式I化合物与除式I以外的β-分泌酶抑制剂，HMG-CoA还原酶抑制剂，γ-分泌酶抑制剂，甾族抗炎剂，N-甲基-D-天冬氨酸受体拮抗剂，胆碱酯酶抑制剂或抗淀粉样蛋白抗体。

47. 发明申请

US20070179187A1 THROMBIN RECEPTOR ANTAGONISTS 有权
标题翻译：硫蛋白受体拮抗剂
公开(公告)号：US20070179187A1
公开(公告)日：2007-08-02
申请号：US11733635
申请日：2007-04-10
申请人： Samuel Chackalamannil , Martin Clasby , William Greenlee , Yuguang Wang , Yan Xia , Enrico Veltri , Mariappan Chelliah
发明人： Samuel Chackalamannil , Martin Clasby , William Greenlee , Yuguang Wang , Yan Xia , Enrico Veltri , Mariappan Chelliah
IPC分类号： A61K31/4433 , C07D405/02
CPC分类号： C07D405/06 , C07D405/14 , C07D417/14
摘要： Heterocyclic-substituted tricyclics of the formula or a pharmaceutically acceptable salt thereof, wherein: the dotted line represents an optional single bond; represents an optional double bond, n is 0-2; Q is cycloalkyl, optionally substituted by R13 and R14; R13 and R14 are independently selected from (C1-C6)alkyl, (C3-C8)cycloalkyl, —OH, (C1-C6)alkoxy, R27-aryl(C1-C6)alkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halogen and haloalkyl; or R13 and R14 together form a spirocyclic or a heterospirocyclic ring of 3-6 atoms, Het is a mono- or bi-cyclic optionally substituted heteroaryl group; and B is a bond, alkylene, or optionally substituted alkenylene or alkynylene, wherein the remaining substituents are as defined in the specification, are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds. Combination therapy with other cardiovascular agents is also claimed.
摘要翻译：具有下式的杂环取代的三环或其药学上可接受的盐，其中：虚线表示任选的单键; “img id =”custom-character-00001“he =”3.13mm“wi =”7.37mm“file =”US20070179187A1-20070802-P00001.TIF“alt =”custom character“img-content =”character“img-format =“tif”/>表示可选的双键，n为0-2; Q是环烷基，任选被R 13和R 14取代; R 13和R 14独立地选自（C 1 -C 6 -C 6）烷基，（C

48. 发明授权

US08278334B2 Cyclic amine BACE-1 inhibitors having a benzamide substituent 有权
标题翻译：具有苯甲酰胺取代基的环胺BACE-1抑制剂
公开(公告)号：US08278334B2
公开(公告)日：2012-10-02
申请号：US12641952
申请日：2009-12-18
申请人： Jared N. Cumming , Ulrich Iserloh , Andrew Stamford , Corey Strickland , Johannes H. Voigt , Yusheng Wu , Ying Huang , Yan Xia , Samuel Chackalamannil , Tao Guo , Douglas W. Hobbs , Thuy X. H. Le , Jeffrey F. Lowrie , Kurt W. Saionz , Suresh D. Babu
发明人： Jared N. Cumming , Ulrich Iserloh , Andrew Stamford , Corey Strickland , Johannes H. Voigt , Yusheng Wu , Ying Huang , Yan Xia , Samuel Chackalamannil , Tao Guo , Douglas W. Hobbs , Thuy X. H. Le , Jeffrey F. Lowrie , Kurt W. Saionz , Suresh D. Babu
IPC分类号： A61K31/4439 , A61K31/40 , A61K31/4025 , C07D207/12 , C07D401/06 , C07D403/12
CPC分类号： C07D243/08 , C07D205/04 , C07D207/08 , C07D207/09 , C07D207/12 , C07D207/26 , C07D209/52 , C07D211/26 , C07D211/46 , C07D217/18 , C07D233/32 , C07D241/04 , C07D241/08 , C07D401/06 , C07D401/10 , C07D401/12 , C07D403/12 , C07D403/14 , C07D409/06 , C07D409/12 , C07D413/06
摘要： Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is R is —C(O)—N(R27)(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I.Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease.Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.
摘要翻译：公开了下式的化合物或其药学上可接受的盐或溶剂化物，其中R1是R是-C（O）-N（R27）（R28），或其余的变量如说明书中所定义。还公开了包含式I化合物的药物组合物。还公开了治疗认知或神经变性疾病如阿尔茨海默病的方法。还公开了治疗认知或神经变性疾病的药物组合物和方法，其包含式I化合物与除式I以外的分泌抑制剂抑制剂，HMG-CoA还原酶抑制剂，γ-分泌酶抑制剂，非 - 甾族抗炎药，N-甲基-D-天冬氨酸受体拮抗剂，胆碱酯酶抑制剂或抗淀粉样蛋白抗体。

49. 发明申请

US20120040975A1 BRIDGED BICYCLIC HETEROCYCLE DERIVATIVES AND METHODS OF USE THEREOF 审中-公开
标题翻译：桥联双环杂环衍生物及其使用方法
公开(公告)号：US20120040975A1
公开(公告)日：2012-02-16
申请号：US13260950
申请日：2010-04-01
申请人： Santhosh Francis Neelamkavil , Bernard R. Neustadt , Andrew Stamford , Yan Xia , Joel M. Harris , Craig D. Boyle , Samuel Chackalamannil , Dipshikha Biswas , Hong Liu , Jinsong Hao , Claire M. Lankin , Unmesh Shah
发明人： Santhosh Francis Neelamkavil , Bernard R. Neustadt , Andrew Stamford , Yan Xia , Joel M. Harris , Craig D. Boyle , Samuel Chackalamannil , Dipshikha Biswas , Hong Liu , Jinsong Hao , Claire M. Lankin , Unmesh Shah
IPC分类号： A61K31/537 , C07D401/12 , C07D491/08 , A61P3/00 , A61K31/506 , C07D487/08 , A61P3/10 , A61P3/04 , C07D451/06 , C07D498/08
CPC分类号： C07D498/08 , C07D401/12 , C07D451/02 , C07D471/08 , C07D487/08 , C07D491/08 , C07D491/113 , C07D495/08
摘要： The present invention relates to Bridged Bicyclic Heterocycle Derivatives, compositions comprising a Bridged Bicyclic Heterocycle Derivative, and methods of using the Bridged Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a GPCR in a patient.
摘要翻译：本发明涉及桥连双环杂环衍生物，包含桥连双环杂环衍生物的组合物和使用桥连双环杂环衍生物用于治疗或预防肥胖，糖尿病，代谢障碍，心血管疾病或与一名患者的GPCR。

50. 发明申请

US20070197628A1 Cannabinoid receptor modulators 失效
标题翻译：大麻素受体调节剂
公开(公告)号：US20070197628A1
公开(公告)日：2007-08-23
申请号：US11653558
申请日：2007-01-16
申请人： Samuel Chackalamannil , Mariappan Chelliah , Martin Clasby , Keith Eagen , Jack Scott , Yuguang Wang , Yan Xia , William Greenlee
发明人： Samuel Chackalamannil , Mariappan Chelliah , Martin Clasby , Keith Eagen , Jack Scott , Yuguang Wang , Yan Xia , William Greenlee
IPC分类号： A61K31/4035 , C07D209/46
CPC分类号： C07D209/46 , C07C233/31 , C07C233/58 , C07C233/59 , C07C233/60 , C07C233/90 , C07D209/44 , C07D209/52 , C07D211/58 , C07D307/83 , C07D401/12 , C07D403/06 , C07D403/12 , C07D405/04 , C07D405/06 , C07D405/12 , C07D409/12 , C07D413/10
摘要： A compound having the general structure of Formula (I): or a pharmaceutically acceptable salt, solvate, or ester thereof, is useful in treating diseases, disorders, or conditions such as obesity, metabolic disorders, addiction, diseases of the central nervous system, cardiovascular disorders, respiratory disorders, and gastrointestinal disorders.
摘要翻译：具有式（I）的通式结构的化合物或其药学上可接受的盐，溶剂化物或酯可用于治疗疾病，病症或病症如肥胖，代谢紊乱，成瘾，中枢神经系统疾病，心血管疾病，呼吸系统疾病和胃肠道疾病。

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