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41. 发明授权

US5955482A Use of 1,4-dihydropyridine-3,5-dicarboxylic acid esters as medicaments 失效
标题翻译：使用1,4-二氢吡啶-3,5-二羧酸酯作为药物
公开(公告)号：US5955482A
公开(公告)日：1999-09-21
申请号：US828464
申请日：1997-03-28
申请人： Klaus Urbahns , Otto Behner , Siegfried Goldmann , Hans-Georg Heine , Bodo Junge , Rudolf Schohe-Loop , Egbert Wehinger , Hartmund Wollweber , Henning Sommermeyer , Thomas Glaser , Reilinde Wittka , Jean-Marie-Viktor de Vry
发明人： Klaus Urbahns , Otto Behner , Siegfried Goldmann , Hans-Georg Heine , Bodo Junge , Rudolf Schohe-Loop , Egbert Wehinger , Hartmund Wollweber , Henning Sommermeyer , Thomas Glaser , Reilinde Wittka , Jean-Marie-Viktor de Vry
IPC分类号： A61K31/435 , A61K31/44 , A61K31/4427 , A61P9/10 , A61P25/00 , A61P43/00 , C07D211/90 , C07D401/04 , C07D211/86
CPC分类号： C07D211/90
摘要： The present invention relates to the use of 1,4-dihydropyridine-3,5-dicarboxylic acid esters, some of which are known, of the general formula (I) ##STR1## in which A and R.sup.1 -R.sup.3 have the meaning given in the description, as medicaments, in particular for treatment of the central nervous system, and new selected active compounds.
摘要翻译：本发明涉及其中一些已知的通式（I）的1,4-二氢吡啶-3,5-二羧酸酯的用途，其中A和R1-R3具有说明书中给出的含义，作为药物，特别是用于治疗中枢神经系统，以及新选择的活性化合物。

42. 发明授权

US5665741A 1,4-dihydropyridine-3,5-dicarboxylic acid esters in treatment of neuronal diseases 失效
标题翻译： 1,4-二氢吡啶-3,5-二羧酸酯治疗神经元疾病
公开(公告)号：US5665741A
公开(公告)日：1997-09-09
申请号：US516668
申请日：1995-08-18
申请人： Klaus Urbahns , Otto Behner , Siegfried Goldmann , Hans-Georg Heine , Bodo Junge , Rudolf Schohe-Loop , Egbert Wehinger , Hartmund Wollweber , Henning Sommermeyer , Thomas Glaser , Reilinde Wittka , Jean-Marie-Viktor de Vry
发明人： Klaus Urbahns , Otto Behner , Siegfried Goldmann , Hans-Georg Heine , Bodo Junge , Rudolf Schohe-Loop , Egbert Wehinger , Hartmund Wollweber , Henning Sommermeyer , Thomas Glaser , Reilinde Wittka , Jean-Marie-Viktor de Vry
IPC分类号： A61K31/435 , A61K31/44 , A61K31/4427 , A61P9/10 , A61P25/00 , A61P43/00 , C07D211/90 , C07D401/04
CPC分类号： C07D211/90
摘要： The present invention relates to the use of 1,4-dihydropyridine-3,5-dicarboxylic acid esters, some of which are known, of the general formula (I) ##STR1## in which A and R.sup.1 -R.sup.3 have the meaning given in the description, as medicaments, in particular for treatment of the central nervous system, and new selected active compounds.
摘要翻译：本发明涉及1,4-二氢吡啶-3,5-二羧酸酯的用途，其中一些是通式（I）的化合物，其中A和R 1 -R 3具有在描述中给出的，作为药物，特别是用于治疗中枢神经系统的药物，以及新的选择的活性化合物。

43. 发明授权

US07511041B2 Fused azole-pyrimidine derivatives 有权
标题翻译：熔融唑 - 嘧啶衍生物
公开(公告)号：US07511041B2
公开(公告)日：2009-03-31
申请号：US10527376
申请日：2003-09-18
申请人： Mitsuyuki Shimada , Toshiki Murata , Kinji Fuchikami , Hideki Tsujishita , Naoki Omori , Issei Kato , Mami Miura , Klaus Urbahns , Florian Gantner , Kevin Bacon
发明人： Mitsuyuki Shimada , Toshiki Murata , Kinji Fuchikami , Hideki Tsujishita , Naoki Omori , Issei Kato , Mami Miura , Klaus Urbahns , Florian Gantner , Kevin Bacon
IPC分类号： A01N43/58 , A01N43/60 , A61K31/50 , A61K31/495 , C07D237/26 , C07D237/36 , C07D241/36 , C07D239/00 , C07D471/00 , C07D471/04 , C07D401/04 , C07D401/22 , C07D487/00 , C07D487/04 , C07D491/00 , C07D495/00 , C07D497/00
CPC分类号： C07D471/14 , C07D487/04
摘要： The present invention relates to hovel fused azolepyrimidine derivatives, processes for preparing them and pharmaceutical preparations containing them. The fused azolepyrimidine derivatives of the present invention exhibit enhanced potency for phosphotidylinositol-3-kinase (PI3K) inhibition, especially for PI3K-γ inhibition and can be used for the prophylaxis and treatment of diseases associated with PI3K and particularly with PI3K-γ activity. More specifically, the azole derivatives of the present invention are useful for treatment and prophylaxis of diseases as follows: inflammatory and immunoregulatory disorders, such as asthma, atopic dermatitis, rhinitis, allergic diseases, chronic obstructive pulmonary disease (COPD), septic shock, joint diseases, autoixnmune pathologies such as rheumatoid arthritis, and Graves' disease, cancer, myocardial contractility disorders, heart failure, thromboembolism, ischemia, and atherosclerosis. The compounds of the present invention are also useful for pulmonary hypertension, renal failure, cardiac hypertrophy, as well as neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, diabetes and focal ischemia, since the diseases also relate to PI3K activity in a human or animal subject.
摘要翻译：本发明涉及霍夫唑唑吡啶衍生物，其制备方法和含有它们的药物制剂。本发明的稠合吡唑嘧啶衍生物对于磷脂酰肌醇-3-激酶（PI3K）抑制的效力显着增强，特别是对于PI3K-γ抑制，可用于预防和治疗与PI3K相关的疾病，特别是PI3K-γ活性。更具体地说，本发明的唑类衍生物可用于治疗和预防以下疾病：炎性和免疫调节性疾病，如哮喘，特应性皮炎，鼻炎，过敏性疾病，慢性阻塞性肺病（COPD），脓毒性休克，关节疾病，自身免疫性疾病如类风湿性关节炎，格雷夫斯病，癌症，心肌收缩性疾病，心力衰竭，血栓栓塞，缺血和动脉粥样硬化。本发明的化合物还可用于肺动脉高压，肾衰竭，心脏肥大，以及神经变性疾病如帕金森病，阿尔茨海默病，糖尿病和局灶性缺血，因为这些疾病还涉及人或动物中的PI3K活性学科。

44. 发明申请

US20090012102A1 Imidazo[1,2-C]Pyrimidinylacetic Acid Derivatives 有权
标题翻译：咪唑并[1,2-C]嘧啶基乙酸衍生物
公开(公告)号：US20090012102A1
公开(公告)日：2009-01-08
申请号：US10585429
申请日：2005-01-19
申请人： Tai-wei Ly , Takashi Yoshino , Yuki Takekawa , Takuya Shintani , Hiromi Sugimoto , Kevin Bacon , Klaus Urbahns
发明人： Tai-wei Ly , Takashi Yoshino , Yuki Takekawa , Takuya Shintani , Hiromi Sugimoto , Kevin Bacon , Klaus Urbahns
IPC分类号： A61K31/519 , C07D487/04 , A61P11/06 , A61P37/08 , A61P35/00
CPC分类号： C07D487/04
摘要： The present invention relates to an imidazo[1,2-c]pyrimidinylacetic acid derivative and salts thereof which is useful as an active ingredient of pharmaceutical preparations. The imidazo[1,2-c]pyrimidinylacetic acid derivative of the present invention has excellent CRTH2 (G-protein-coupled chemoattractant receptor, expressed on Th2 cells) antagonistic activity and can be used for the prophylaxis and treatment of diseases associated with CRTH2 activity, in particular for the treatment of allergic diseases, such as asthma, allergic rhinitis, atopic dermatitis, and allergic conjunctivitis; eosinophil-related diseases, such as Churg-Strauss syndrome and sinusitis; basophil-related diseases, such as basophilic leukemia, chronic urticaria and basophilic leukocytosis in human and other mammals; and inflammatory diseases characterized by T lymphocytes and profuse leukocyte infiltrates such as psoriasis, eczema, inflammatory bowel disease, ulcerative colitis, Crohn's disease, COPD (chronic obstructive pulmonary disorder) and arthritis.
摘要翻译：本发明涉及可用作药物制剂活性成分的咪唑并[1,2-c]嘧啶基乙酸衍生物及其盐。本发明的咪唑并[1,2-c]嘧啶基乙酸衍生物具有优异的CRTH2（G蛋白偶联化学引诱物受体，在Th2细胞上表达）拮抗活性，可用于预防和治疗与CRTH2活性相关的疾病特别是用于治疗过敏性疾病如哮喘，过敏性鼻炎，特应性皮炎和过敏性结膜炎; 嗜酸性粒细胞相关疾病，如中华综合征和鼻窦炎; 嗜碱性粒细胞相关疾病，如嗜碱性白血病，慢性荨麻疹和人类和其他哺乳动物的嗜碱性白细胞增多症; 以T淋巴细胞为特征的炎性疾病和白血球浸润如银屑病，湿疹，炎性肠病，溃疡性结肠炎，克罗恩病，COPD（慢性阻塞性肺病）和关节炎等。

45. 发明授权

US07423175B2 Hydroxy-tetrahydro-naphthalenylurea derivatives 失效
标题翻译：羟基 - 四氢 - 萘基脲衍生物
公开(公告)号：US07423175B2
公开(公告)日：2008-09-09
申请号：US10545556
申请日：2004-02-05
申请人： Takeshi Yura , Muneto Mogi , Hiroshi Fujishima , Klaus Urbahns , Tsutomu Masuda , Yasuhiro Tsukimi , Masaomi Tajimi , Noriyuki Yamamoto , Nagahiro Yoshida , Toshiya Moriwaki
发明人： Takeshi Yura , Muneto Mogi , Hiroshi Fujishima , Klaus Urbahns , Tsutomu Masuda , Yasuhiro Tsukimi , Masaomi Tajimi , Noriyuki Yamamoto , Nagahiro Yoshida , Toshiya Moriwaki
IPC分类号： C07C275/32 , A61K31/17
CPC分类号： C07D295/096 , C07C275/32 , C07C2602/10
摘要： This invention relates to hydroxy-tetrahydro-naphthalenylurea derivatives and salts thereof which are useful as active ingredients of pharmaceutical preparations. The hydroxy-tetrahydro-naphthalenylurea derivatives of the present invention have an excellent activity as VR1 antagonist and are useful for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urinary incontinence, urge urinary incontinence, overactive bladder, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, inflammatory disorders, asthma and COPD.
摘要翻译：本发明涉及可用作药物制剂活性成分的羟基 - 四氢 - 萘基脲衍生物及其盐。本发明的羟基 - 四氢 - 萘基脲衍生物作为VR1拮抗剂具有优异的活性，并且可用于预防和治疗与VR1活性有关的疾病，特别是用于治疗尿失禁，敦促性尿失禁，膀胱过度活动症，慢性疼痛，神经性疼痛，术后疼痛，类风湿关节炎疼痛，神经痛，神经病，痛觉，神经损伤，局部缺血，神经变性，中风，炎性疾病，哮喘和COPD。

46. 发明申请

US20080058377A1 Bicyclic Amide, Carbamate or Urea Derivatives as Vanilloid Receptor Modulators 审中-公开
标题翻译：双环酰胺，氨基甲酸酯或尿素衍生物作为香草酸受体调节剂
公开(公告)号：US20080058377A1
公开(公告)日：2008-03-06
申请号：US10578490
申请日：2004-10-26
申请人： Muneto Mogi , Hiroshi Fujishima , Masaomi Tajimi , Noriyuki Yamamoto , Klaus Urbahns , Fumihiko Hayashi , Yasuhiro Tsukimi , Jang Gupta , Hiroaki Yuasa
发明人： Muneto Mogi , Hiroshi Fujishima , Masaomi Tajimi , Noriyuki Yamamoto , Klaus Urbahns , Fumihiko Hayashi , Yasuhiro Tsukimi , Jang Gupta , Hiroaki Yuasa
IPC分类号： A61K31/445 , A61K31/16 , A61K31/17 , A61P29/00 , C07C275/28 , C07C233/00 , A61P13/00 , A61K31/195
CPC分类号： C07D295/155 , C07C235/38 , C07C275/32 , C07C2601/14 , C07C2602/08 , C07C2602/10
摘要： This invention relates to bicyclic amide, carbamate or urea derivatives and salts thereof which are useful as active ingredients of pharmaceutical preparations. The bicyclic amide, carbamate or urea derivative of the present invention has vanilloid receptor (VR1) antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urological diseases or disorders, such as detrusor overactivity (overactive bladder), urinary incontinence, neurogenic detrusor oeractivity (detrusor hyperflexia), idiopathic detrusor overactivity (detrusor instability), benign prostatic hyperplasia, and lower urinary tract symptoms; chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, and inflammatory disorders such as asthma and chronic obstructive pulmonary (or airways) disease (COPD).
摘要翻译：本发明涉及可用作药物制剂活性成分的双环酰胺，氨基甲酸酯或脲衍生物及其盐。本发明的双环酰胺，氨基甲酸酯或尿素衍生物具有香草素受体（VR1）拮抗活性，可用于预防和治疗与VR1活性有关的疾病，特别是用于治疗泌尿系统疾病或病症，例如逼尿肌过度活动症（膀胱过度活动症），尿失禁，神经源性逼尿肌过敏反应（逼尿肌hyperflexia），特发性逼尿肌过度活动（逼尿肌不稳定），良性前列腺增生和下尿路症状; 慢性疼痛，神经性疼痛，术后疼痛，类风湿性关节炎疼痛，神经痛，神经病，痛觉，神经损伤，局部缺血，神经变性，中风和炎性疾病如哮喘和慢性阻塞性肺（或气道）疾病（COPD）。

47. 发明申请

US20070155725A1 2-Phenoxy- and 2-phenylsulfomamide derivatives with ccr3 antagonistic activity for the treatment of asthma and other inflammatory or immunological disorders 有权
标题翻译：具有ccr3拮抗活性的2-苯氧基-2-苯磺酰胺衍生物，用于治疗哮喘和其他炎性或免疫性疾病
公开(公告)号：US20070155725A1
公开(公告)日：2007-07-05
申请号：US10550482
申请日：2004-03-11
申请人： Yingfu Li , Kevin Bacon , Hiromi Sugimoto , Keiko Fukushima , Kentaro Hashimoto , Makiko Marumo , Toshiya Moriwaki , Noriko Nunami , Naoki Tsuno , Klaus Urbahns , Nagahiro Yoshida
发明人： Yingfu Li , Kevin Bacon , Hiromi Sugimoto , Keiko Fukushima , Kentaro Hashimoto , Makiko Marumo , Toshiya Moriwaki , Noriko Nunami , Naoki Tsuno , Klaus Urbahns , Nagahiro Yoshida
IPC分类号： A61K31/551 , A61K31/495 , A61K31/4745 , A61K31/445 , A61K31/4025 , A61K31/18 , C07D211/54 , C07D403/02 , C07D453/02
CPC分类号： C07D487/04 , A61K31/439 , C07C311/29 , C07D207/12 , C07D207/14 , C07D207/16 , C07D207/40 , C07D207/404 , C07D207/48 , C07D211/54 , C07D223/12 , C07D241/04 , C07D243/08 , C07D257/04 , C07D295/13 , C07D295/22 , C07D295/26 , C07D303/06 , C07D303/36 , C07D401/04 , C07D401/06 , C07D401/14 , C07D403/06 , C07D403/12 , C07D453/02 , C07D487/02 , C07D487/08
摘要： The present invention relates to a benzenesulfonamide derivative of formula (I), which is useful as an active ingredient of pharmaceutical preparations. The benzenesulfonamide derivatives of the present invention have CCR3 (CC type chemokine receptor) antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with CCR3 activity, in particular for the treatment of asthma, atopic dermatitis, allergic rhinitis and other inflammatory/immunological disorders. In said formula, X represents O or S; R4 represents formulae (a), (b), (c), (d), (e), (f), (g), (h), (i) or (j), the other substituents are as defined in claim 1.
摘要翻译：本发明涉及式（I）的苯磺酰胺衍生物，其可用作药物制剂的活性成分。本发明的苯磺酰胺衍生物具有CCR3（CC型趋化因子受体）拮抗活性，可用于预防和治疗与CCR3活性有关的疾病，特别是用于治疗哮喘，特应性皮炎，过敏性鼻炎等炎症 /免疫学障碍。在所述式中，X表示O或S; R 4表示式（a），（b），（c），（d），（e），（f），（g），（h），（i）或（j），其它取代基如权利要求1中所定义。

48. 发明申请

US20060135505A1 Tetrahydro-naphthalene derivatives as vanilloid receptor antagonists 失效
公开(公告)号：US20060135505A1
公开(公告)日：2006-06-22
申请号：US10537217
申请日：2003-11-28
申请人： Masaomi Tajimi , Toshio Kokubo , Masahiro Shiroo , Yasuhiro Tsukimi , Takeshi Yura , Klaus Urbahns , Noriyuki Yamamoto , Muneto Mogi , Hiroshi Fujishima , Tsutomu Masuda , Nagahiro Yoshida , Toshiya Moriwaki
发明人： Masaomi Tajimi , Toshio Kokubo , Masahiro Shiroo , Yasuhiro Tsukimi , Takeshi Yura , Klaus Urbahns , Noriyuki Yamamoto , Muneto Mogi , Hiroshi Fujishima , Tsutomu Masuda , Nagahiro Yoshida , Toshiya Moriwaki
IPC分类号： A61K31/445 , A61K31/40 , A61K31/397 , A61K31/17
CPC分类号： C07C275/32 , C07C2602/10 , C07D207/27 , C07D211/22 , C07D211/46 , C07D211/62 , C07D295/135
摘要： This invention relates to tetrahydro-naphthalene derivatives of formula (I) in which the variable groups are as defined in the specification and claims, and tautomeric and stereoisomeric forms and salts thereof which are useful as active ingredients of pharmaceutical preparations. The tetrahydro-naphthalene derivatives of the present invention have an excellent activity as VR1 antagonists and are useful for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urinary incontinence, urge urinary incontinence, overactive bladder, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, inflammatory disorders, asthma and COPD. The compounds, pharmaceutical compositions containing them, and methods of treatment using them are disclosed and claimed.

49. 发明申请

US20060128732A1 Fused azole-pyrimidine derivatives 有权
公开(公告)号：US20060128732A1
公开(公告)日：2006-06-15
申请号：US10527376
申请日：2003-09-18
申请人： Mitsuyuki Shimada , Toshiki Murata , Kinji Fuchikami , Hideki Tsujishita , Naoki Omori , Issei Kato , Mami Miura , Klaus Urbahns , florian Gantner , Kevin Bacon
发明人： Mitsuyuki Shimada , Toshiki Murata , Kinji Fuchikami , Hideki Tsujishita , Naoki Omori , Issei Kato , Mami Miura , Klaus Urbahns , florian Gantner , Kevin Bacon
IPC分类号： A61K31/519 , C07D487/14
CPC分类号： C07D471/14 , C07D487/04
摘要： The present invention relates to hovel fused azolepyrimidine derivatives, processes for preparing them and pharmaceutical preparations containing them. The fused azolepyrimidine derivatives of the present invention exhibit enhanced potency for phosphotidylinositol-3-kinase (PI3K) inhibition, especially for PI3K-γ inhibition and can be used for the prophylaxis and treatment of diseases associated with PI3K and particularly with PI3K-γ activity. More specifically, the azole derivatives of the present invention are useful for treatment and prophylaxis of diseases as follows: inflammatory and immunoregulatory disorders, such as asthma, atopic dermatitis, rhinitis, allergic diseases, chronic obstructive pulmonary disease (COPD), septic shock, joint diseases, autoixnmune pathologies such as rheumatoid arthritis, and Graves' disease, cancer, myocardial contractility disorders, heart failure, thromboembolism, ischemia, and atherosclerosis. The compounds of the present invention are also useful for pulmonary hypertension, renal failure, cardiac hypertrophy, as well as neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, diabetes and focal ischemia, since the diseases also relate to PI3K activity in a human or animal subject.

50. 发明申请

US20050154230A1 Urea derivatives 审中-公开
标题翻译：尿素衍生物
公开(公告)号：US20050154230A1
公开(公告)日：2005-07-14
申请号：US10499785
申请日：2002-12-13
申请人： Takeshi Yura , Muneto Mogi , Yuka Ikegami , Tsutomu Masuda , Toshio Kokubo , Klaus Urbahns , Nagahiro Yoshida , Makiko Marumo , Masahiro Shiroo , Masaomi Tajimi , Keisuke Takeshita , Toshiya Moriwaki , Yasuhiro Tsukimi
发明人： Takeshi Yura , Muneto Mogi , Yuka Ikegami , Tsutomu Masuda , Toshio Kokubo , Klaus Urbahns , Nagahiro Yoshida , Makiko Marumo , Masahiro Shiroo , Masaomi Tajimi , Keisuke Takeshita , Toshiya Moriwaki , Yasuhiro Tsukimi
IPC分类号： C07D295/12 , A61K31/167 , A61K31/17 , A61K31/216 , A61K31/277 , A61K31/341 , A61K31/36 , A61K31/381 , A61K31/403 , A61K31/416 , A61K31/44 , A61K31/4406 , A61K31/4453 , A61K31/47 , A61K31/472 , A61K31/496 , A61P9/10 , A61P13/10 , A61P25/00 , A61P25/04 , A61P25/28 , A61P29/00 , A61P29/02 , A61P43/00 , C07C275/10 , C07C275/24 , C07C275/28 , C07C275/30 , C07C275/32 , C07C275/34 , C07C275/36 , C07C275/38 , C07C275/40 , C07C275/42 , C07C323/33 , C07C323/43 , C07D209/88 , C07D213/40 , C07D213/75 , C07D215/38 , C07D217/06 , C07D231/56 , C07D295/135 , C07D307/52 , C07D317/06 , C07D317/58 , C07D317/66 , C07D333/20 , C07D333/36
CPC分类号： C07D333/36 , C07C275/24 , C07C275/28 , C07C275/30 , C07C275/32 , C07C275/40 , C07C275/42 , C07C323/43 , C07C2602/10 , C07C2603/18 , C07D209/88 , C07D213/40 , C07D213/75 , C07D217/06 , C07D231/56 , C07D295/135 , C07D307/52 , C07D317/06 , C07D317/58 , C07D333/20
摘要： This invention relates to urea derivatives and salts thereof which is useful as an active ingredient of pharmaceutical preparations. The urea derivatives of the present invention has an excellent activity as VR1 antagonist and useful for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urge urinary incontinence, overactive bladder, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, incontinence and/or inflammatory disorders.
摘要翻译：本发明涉及尿素衍生物及其盐，其可用作药物制剂的活性成分。本发明的脲衍生物作为VR1拮抗剂具有优异的活性，可用于预防和治疗与VR1活性相关的疾病，特别是用于治疗急性尿失禁，膀胱过度活动症，慢性疼痛，神经性疼痛，术后疼痛，类风湿性关节炎疼痛，神经痛，神经病，酸痛，神经损伤，局部缺血，神经变性，中风，失禁和/或炎症性疾病。

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