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1. 发明授权

US06258844B1 Cyclopentane (ene) oic acid, 2-alkenyl derivatives as therapeutic agents 失效
标题翻译：环戊烷（烯）酸，2-烯基衍生物作为治疗剂
公开(公告)号：US06258844B1
公开(公告)日：2001-07-10
申请号：US09194457
申请日：1998-11-24
申请人： Michael E. Garst , Michael B. Roof , Ming F. Chan , David F. Woodward , Robert M. Burk , Todd S. Gac , Steven W. Andrews
发明人： Michael E. Garst , Michael B. Roof , Ming F. Chan , David F. Woodward , Robert M. Burk , Todd S. Gac , Steven W. Andrews
IPC分类号： A67K31215
CPC分类号： A61K31/5575 , C07C405/00 , Y10S514/913
摘要： The invention relates to the use of omega chain modified prostaglandins as ocular hypotensive. The derivatives used in accordance with the invention are encompassed by the following structure formula I: wherein the hatched segments represent &agr; bonds; the wavy segment represents an &agr; or &bgr; bond; dashed lines represent a double bond or a single bond; X is selected from the group consisting of —OR and N(R2); Y is=O or represents 2 hydrogen radicals, provided that Y represents 2 hydrogen radicals when X is OH; R is hydrogen or a lower alkyl radical having up to six carbon atoms; R1 is=O or hydroxy; m is 0, 2, 4 or 6, provided that m is not 4 when the wavy segment represents a &bgr; bond; n is 0, 2, 4 or 6; x and y are 0 or 1, provided that x is 1 when y is 0 and y is 1 when x is 0; or 9, 11 and/or 15 ester derivatives of said compound of formula I, e.g. a C1 to C6 alkyl ester derivative; or a pharmaceutically acceptable salt thereof. In a further aspect, the present invention relates to an ophthalmic solution comprising a therapeutically effective amount of a compound of formula (I), wherein the symbols have the above meanings, in admixture with a non-toxic, ophthalmically acceptable liquid vehicle, packaged in a container suitable for metered application.
摘要翻译：本发明涉及使用ω-链修饰的前列腺素作为眼压降低。根据本发明使用的衍生物包括下列结构式I：其中阴影线段代表α键; 波浪段表示α或β键; 虚线表示双键或单键; X选自-OR和N（R2）; Y为= O或表示2个氢原子，条件是当X为OH时，Y表示2个氢原子; R是氢或具有至多6个碳原子的低级烷基; R1为= O或羟基; m为0,2,4或6，条件是当波浪段代表β键时m不为4; n为0,2,4或6; x和y为0或1，条件是当y为0时x为1，当x为0时y为1; 或所述式I化合物的9,11和/或15酯衍生物，例如。 C1-C6烷基酯衍生物; 或其药学上可接受的盐。在另一方面，本发明涉及一种眼用溶液，其包含治疗有效量的式（I）化合物，其中符号具有上述含义，与无毒的眼科可接受的液体载体混合，包装在适用于计量应用的容器。

2. 发明申请

US20130324606A1 Ester Derivatives of Bimatoprost Compositions and Methods 审中-公开
标题翻译：比马前列素组合物和方法的酯衍生物
公开(公告)号：US20130324606A1
公开(公告)日：2013-12-05
申请号：US13985263
申请日：2012-02-13
申请人： David F. Woodward , Jenny W. Wang , Neil J. Poloso , Todd S. Gac , Robert M. Burk , Michael E. Garst
发明人： David F. Woodward , Jenny W. Wang , Neil J. Poloso , Todd S. Gac , Robert M. Burk , Michael E. Garst
IPC分类号： C07C405/00
CPC分类号： C07C235/34 , A61K8/42 , A61Q7/00 , C07C405/00 , C07C405/0041 , C07C2601/08
摘要： Provided herein, inter alia, are prodrugs of bimatoprost, methods of using the same and compositions including the same.
摘要翻译：本文提供的是比马前列素的前药，其使用方法和包含其的组合物。

3. 发明申请

US20090227672A1 NON-ACIDIC CYCLOPENTANE HEPTANOIC ACID, 2-CYCLOALKYL OR ARYLALKYL DERIVATIVES AS THERAPEUTIC AGENTS 有权
标题翻译：非酸性环戊二烯酸，作为治疗剂的2-环烯基或亚苄基衍生物
公开(公告)号：US20090227672A1
公开(公告)日：2009-09-10
申请号：US12339494
申请日：2008-12-19
申请人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
发明人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
IPC分类号： A61K31/215 , A61K31/192 , A61P27/06
CPC分类号： A61K31/559 , A61K31/381 , A61K31/557 , A61K31/5575 , A61K31/5585 , C07C35/21 , C07C215/42 , C07C235/34 , C07C247/10 , C07C255/36 , C07C405/00 , C07C2601/08 , Y10S514/913
摘要： The present invention provides cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compounds, which may be substituted in the 1-position with amino, amido, ether or ester groups, e.g., a 1-OH cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compound. The cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma. Moreover, the cyclopentane heptanoic, 2-(cycloalkyl or arylalkyl) compounds of this invention are smooth muscle relaxants with broad application in systemic hypertensive and pulmonary diseases; smooth muscle relaxants with application in gastrointestinal disease, reproduction, fertility, incontinence, shock, etc.
摘要翻译：本发明提供环戊烷庚酸，2-环烷基或芳基烷基化合物，其可以在1-位被氨基，酰氨基，醚或酯基取代，例如1-OH环戊烷庚酸，2-（环烷基或芳烷基）化合物。本发明的环戊烷庚酸2-（环烷基或芳基烷基）化合物是有效的眼部低血压剂，特别适用于治疗青光眼。此外，本发明的环戊烷庚酸，2-（环烷基或芳基烷基）化合物是广泛应用于全身高血压和肺部疾病的平滑肌松弛剂; 平滑肌松弛剂适用于胃肠道疾病，繁殖，生育，失禁，休克等。

4. 发明授权

US06403649B1 Non-acidic cyclopentane heptanoic acid,2-cycloalkyl or arylalkyl derivatives as therapeutic agents 失效
标题翻译：非酸性环戊烷庚酸，2-环烷基或芳烷基衍生物作为治疗剂
公开(公告)号：US06403649B1
公开(公告)日：2002-06-11
申请号：US09519834
申请日：2000-03-06
申请人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
发明人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
IPC分类号： A61K31135
CPC分类号： A61K31/559 , A61K31/381 , A61K31/557 , A61K31/5575 , A61K31/5585 , C07C35/21 , C07C215/42 , C07C235/34 , C07C247/10 , C07C255/36 , C07C405/00 , C07C2601/08 , Y10S514/913
摘要： The present invention provides cydopentane heptanoic acid, 2-cycloalkyl or arylalkyl compounds, which may be substituted in the 1-position with amino, amido, ether or ester groups, e.g., a 1-OH cydopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compound. The cydopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma. Moreover, the cydopentane heptanoic, 2-(cycloalkyl or arylalkyl) compounds of this invention are smooth muscle relaxants with broad application in systemic hypertensive and pulmonary diseases; smooth muscle relaxants with application in gastrointestinal disease, reproduction, fertility, incontinence, shock, etc.
摘要翻译：本发明提供环戊烷庚酸，2-环烷基或芳基烷基化合物，其可以在1-位被氨基，酰氨基，醚或酯基取代，例如1-OH环戊烷庚酸，2-（环烷基或芳烷基）化合物。本发明的环戊烷庚酸2-（环烷基或芳基烷基）化合物是有效的眼部低血压剂，特别适用于治疗青光眼。此外，本发明的环戊烷庚酸，2-（环烷基或芳基烷基）化合物是广泛应用于全身高血压和肺部疾病的平滑肌松弛剂; 平滑肌松弛剂适用于胃肠道疾病，繁殖，生育，失禁，休克等。

5. 发明授权

US5688819A Cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents 失效
标题翻译：非酸性环戊烷庚酸，2-环烷基或芳烷基衍生物作为治疗剂
公开(公告)号：US5688819A
公开(公告)日：1997-11-18
申请号：US605567
申请日：1996-02-22
申请人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
发明人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
IPC分类号： A61K31/557 , A61K31/5575 , C07C35/21 , C07C215/42 , C07C235/34 , C07C247/10 , C07C255/36 , C07C405/00 , A61K31/135 , A61K31/34 , A61K31/38 , A61K31/44
CPC分类号： A61K31/559 , A61K31/557 , A61K31/5575 , C07C215/42 , C07C235/34 , C07C247/10 , C07C255/36 , C07C35/21 , C07C405/00 , C07C2101/08
摘要： The present invention provides cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compounds, which may be substituted in the 1-position with amino, amido, ether or ester groups, e.g., a 1-OH cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compound. The cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma. Moreover, the cyclopentane heptanoic, 2-(cycloalkyl or arylalkyl) compounds of this invention are smooth muscle relaxants with broad application in systemic hypertensive and pulmonary diseases; smooth muscle relaxants with application in gastrointestinal disease, reproduction, fertility, incontinence, shock, etc.
摘要翻译：本发明提供环戊烷庚酸，2-环烷基或芳基烷基化合物，其可以在1位被氨基，酰胺基，醚或酯基取代，例如1-OH环戊烷庚酸，2-（环烷基或芳烷基）化合物。本发明的环戊烷庚酸2-（环烷基或芳基烷基）化合物是有效的眼部低血压剂，特别适用于治疗青光眼。此外，本发明的环戊烷庚酸，2-（环烷基或芳基烷基）化合物是广泛应用于全身高血压和肺部疾病的平滑肌松弛剂; 平滑肌松弛剂适用于胃肠道疾病，繁殖，生育，失禁，休克等。

6. 发明授权

US5352708A Non-acidic cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents 失效
标题翻译：非酸性环戊烷庚酸，2-环烷基或芳烷基衍生物作为治疗剂
公开(公告)号：US5352708A
公开(公告)日：1994-10-04
申请号：US948056
申请日：1992-09-21
申请人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
发明人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
IPC分类号： A61K31/045 , A61K31/075 , A61K31/13 , A61K31/16 , A61K31/275 , A61K31/381 , A61K31/557 , A61K31/5575 , A61K31/5585 , A61K31/655 , A61P1/00 , A61P1/16 , A61P9/00 , A61P11/00 , A61P13/02 , A61P15/00 , A61P27/02 , A61P27/06 , A61P27/14 , A61P37/08 , A61P43/00 , C07C35/21 , C07C35/50 , C07C69/732 , C07C69/734 , C07C205/17 , C07C215/42 , C07C235/34 , C07C247/10 , C07C255/36 , C07C405/00
CPC分类号： A61K31/559 , A61K31/381 , A61K31/557 , A61K31/5575 , A61K31/5585 , C07C215/42 , C07C235/34 , C07C247/10 , C07C255/36 , C07C35/21 , C07C405/00 , C07C2101/08
摘要： The present invention provides cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives, substituted in the 1-position with halo, methyl, hydroxyl, nitro, amino, amido, azido, oxime, cyano, thiol, either or thioether groups, e.g., a 1-OH cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) derivatives. The cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) derivatives of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma. Moreover, the cyclopentane heptanoic, 2-(cycloalkyl or arylalkyl) derivatives of this invention are smooth muscle relaxants with broad application in systemic hypertensive and pulmonary diseases; smooth muscle relaxants with application in gastrointestinal disease, reproduction, fertility, incontinence, shock, etc.
摘要翻译：本发明提供在1-位被卤素，甲基，羟基，硝基，氨基，酰氨基，叠氮基，肟，氰基，硫醇，或硫醚基取代的环戊烷庚酸，2-环烷基或芳基烷基衍生物，例如 1-OH环戊烷庚酸，2-（环烷基或芳基烷基）衍生物。本发明的环戊烷庚酸，2-（环烷基或芳基烷基）衍生物是有效的眼睛低血压剂，特别适用于治疗青光眼。此外，本发明的环戊烷庚酸，2-（环烷基或芳基烷基）衍生物是广泛应用于全身高血压和肺部疾病的平滑肌松弛剂; 平滑肌松弛剂适用于胃肠道疾病，繁殖，生育，失禁，休克等。

7. 发明授权

US5607978A Non-acidic cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents 失效
标题翻译：非酸性环戊烷庚酸，2-环烷基或芳烷基衍生物作为治疗剂
公开(公告)号：US5607978A
公开(公告)日：1997-03-04
申请号：US371339
申请日：1995-01-11
申请人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
发明人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
IPC分类号： A61K31/045 , A61K31/075 , A61K31/13 , A61K31/16 , A61K31/275 , A61K31/381 , A61K31/557 , A61K31/5575 , A61K31/5585 , A61K31/655 , A61P1/00 , A61P1/16 , A61P9/00 , A61P11/00 , A61P13/02 , A61P15/00 , A61P27/02 , A61P27/06 , A61P27/14 , A61P37/08 , A61P43/00 , C07C35/21 , C07C35/50 , C07C69/732 , C07C69/734 , C07C205/17 , C07C215/42 , C07C235/34 , C07C247/10 , C07C255/36 , C07C405/00 , A61K31/135 , A61K31/34 , A61K31/38 , A61K31/44
CPC分类号： A61K31/559 , A61K31/381 , A61K31/557 , A61K31/5575 , A61K31/5585 , C07C215/42 , C07C235/34 , C07C247/10 , C07C255/36 , C07C35/21 , C07C405/00 , C07C2101/08
摘要： The present invention provides cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives, substituted in the 1-position with halo, methyl, hydroxyl, nitro, amino, amido, azido, oxime, cyano, thiol, either or thioether groups, e.g., a 1-OH cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) derivatives. The cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) derivatives of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma. Moreover, the cyclopentane heptanoic, 2-(cycloalkyl or arylalkyl) derivatives of this invention are smooth muscle relaxants with broad application in systemic hypertensive and pulmonary diseases; smooth muscle relaxants with application in gastrointestinal disease, reproduction, fertility, incontinence, shock, etc.
摘要翻译：本发明提供在1-位被卤素，甲基，羟基，硝基，氨基，酰氨基，叠氮基，肟，氰基，硫醇，或硫醚基取代的环戊烷庚酸，2-环烷基或芳基烷基衍生物，例如 1-OH环戊烷庚酸，2-（环烷基或芳基烷基）衍生物。本发明的环戊烷庚酸，2-（环烷基或芳基烷基）衍生物是有效的眼睛低血压剂，特别适用于治疗青光眼。此外，本发明的环戊烷庚酸，2-（环烷基或芳基烷基）衍生物是广泛应用于全身高血压和肺部疾病的平滑肌松弛剂; 平滑肌松弛剂适用于胃肠道疾病，繁殖，生育，失禁，休克等。

8. 发明申请

US20110294893A1 NON-ACIDIC CYCLOPENTANE HEPTANOIC ACID, 2-CYCLOALKYL OR ARYLALKYL DERIVATIVES AS THERAPEUTIC AGENTS 审中-公开
标题翻译：非酸性环戊二烯酸，作为治疗剂的2-环烯基或亚苄基衍生物
公开(公告)号：US20110294893A1
公开(公告)日：2011-12-01
申请号：US13205220
申请日：2011-08-08
申请人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
发明人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
IPC分类号： A61K31/165 , A61P27/06 , A61P27/02
CPC分类号： A61K31/559 , A61K31/381 , A61K31/557 , A61K31/5575 , A61K31/5585 , C07C35/21 , C07C215/42 , C07C235/34 , C07C247/10 , C07C255/36 , C07C405/00 , C07C2601/08 , Y10S514/913
摘要： The present invention provides cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compounds, which may be substituted in the 1-position with amino, amido, ether or ester groups, e.g., a 1-OH cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compound. The cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma. Moreover, the cyclopentane heptanoic, 2-(cycloalkyl or arylalkyl) compounds of this invention are smooth muscle relaxants with broad application in systemic hypertensive and pulmonary diseases; smooth muscle relaxants with application in gastrointestinal disease, reproduction, fertility, incontinence, shock, etc.
摘要翻译：本发明提供环戊烷庚酸，2-环烷基或芳基烷基化合物，其可以在1-位被氨基，酰氨基，醚或酯基取代，例如1-OH环戊烷庚酸，2-（环烷基或芳烷基）化合物。本发明的环戊烷庚酸2-（环烷基或芳基烷基）化合物是有效的眼部低血压剂，特别适用于治疗青光眼。此外，本发明的环戊烷庚酸，2-（环烷基或芳基烷基）化合物是广泛应用于全身高血压和肺部疾病的平滑肌松弛剂; 平滑肌松弛剂适用于胃肠道疾病，繁殖，生育，失禁，休克等。

9. 发明授权

US08017655B2 Non-acidic cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents 有权
标题翻译：非酸性环戊烷庚酸，2-环烷基或芳烷基衍生物作为治疗剂
公开(公告)号：US08017655B2
公开(公告)日：2011-09-13
申请号：US12339494
申请日：2008-12-19
申请人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
发明人： David F. Woodward , Steven W. Andrews , Robert M. Burk , Michael E. Garst
IPC分类号： A61K31/215 , A61K31/205 , A61K31/19 , A61K31/165
CPC分类号： A61K31/559 , A61K31/381 , A61K31/557 , A61K31/5575 , A61K31/5585 , C07C35/21 , C07C215/42 , C07C235/34 , C07C247/10 , C07C255/36 , C07C405/00 , C07C2601/08 , Y10S514/913
摘要： The present invention provides cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compounds, which may be substituted in the 1-position with amino, amido, ether or ester groups, e.g., a 1-OH cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compound. The cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma. Moreover, the cyclopentane heptanoic, 2-(cycloalkyl or arylalkyl) compounds of this invention are smooth muscle relaxants with broad application in systemic hypertensive and pulmonary diseases; smooth muscle relaxants with application in gastrointestinal disease, reproduction, fertility, incontinence, shock, etc.
摘要翻译：本发明提供环戊烷庚酸，2-环烷基或芳基烷基化合物，其可以在1-位被氨基，酰氨基，醚或酯基取代，例如1-OH环戊烷庚酸，2-（环烷基或芳烷基）化合物。本发明的环戊烷庚酸2-（环烷基或芳基烷基）化合物是有效的眼部低血压剂，特别适用于治疗青光眼。此外，本发明的环戊烷庚酸，2-（环烷基或芳基烷基）化合物是广泛应用于全身高血压和肺部疾病的平滑肌松弛剂; 平滑肌松弛剂适用于胃肠道疾病，繁殖，生育，失禁，休克等。

10. 发明授权

US5476872A 1,11-diesters of prostaglandin-F.sub.2.alpha. having a polar ester group at C-1 失效
标题翻译：在C-1具有极性酯基的前列腺素-F1α的1,11-二酯
公开(公告)号：US5476872A
公开(公告)日：1995-12-19
申请号：US138274
申请日：1993-10-18
申请人： Michael E. Garst , Elizabeth T. Syage , Michael B. Roof , David F. Woodward , Ming Fai Chan
发明人： Michael E. Garst , Elizabeth T. Syage , Michael B. Roof , David F. Woodward , Ming Fai Chan
IPC分类号： A61K31/557 , A61K31/5575 , A61P27/02 , C07C405/00
CPC分类号： A61K31/557 , C07C405/00
摘要： Compounds of the formula ##STR1## where the hatched lines indicate alpha (.alpha.) configuration, a solid triangle is used to indicate beta (.beta.) configuration, lines on both sides of a double bond indicate cis (Z) configuration, and lines on opposite sides of the double bond indicate trans (E) configuration; R.sub.1 is alkyl of 1-10 carbons, C.sub.1 -C.sub.10 alkylphenyl, phenyl-C.sub.1 -C.sub.10 alkyl, or alkenyl of 2 to 10 carbons and having 1 to 3 double bonds; R.sub.2 is Z--OR.sub.3, Z--OCOR.sub.3, Z--OCONHR.sub.3, Z--OCOOR.sub.3, Z--NR.sub.4 R.sub.5, Z--NR.sub.4 COR.sub.3, Z--NR.sub.4 SO.sub.2 R.sub.3, Z--COOR.sub.3, Z--CONR.sub.4 R.sub.5, Z--CHO; Z is (CH.sub.2).sub.n where n is 1-6, or Z is an alkenyl group having 2 to 6 carbons and 1 or 2 double bonds, R.sub.3 is H, alkyl of 1-6 carbons, alkenyl of 2 to 6 carbons or phenyl, R.sub.4 and R.sub.5 independently are H or alkyl of 1 to 6 carbons, have ocular hypotensive activity.
摘要翻译：阴影线表示α（α）构型，实心三角形用于表示β（β）构型的公式“IMAGE”的化合物，双键两侧的线表示顺式（Z）构型，而相反的线双键表示反式（E）配置; R 1是1-10个碳的烷基，C 1 -C 10烷基苯基，苯基-C 1 -C 10烷基或2至10个碳的烯基并具有1至3个双键; R2是Z-OR3，Z-OCOR3，Z-OCONHR3，Z-OCOOR3，Z-NR4R5，Z-NR4COR3，Z-NR4SO2R3，Z-COOR3，Z-CONR4R5，Z-CHO; Z是（CH 2）n，其中n是1-6，或Z是具有2至6个碳的烯基和1或2个双键，R3是H，1-6个碳原子的烷基，2至6个碳原子的链烯基或苯基，R4和R5独立地是H或1至6个碳的烷基，具有眼睛低血压活性。

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