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1. 发明公开

EP0180921A3 Process for the preparation and purification of peptides 失效
标题翻译：肽的制备和纯化方法
公开(公告)号：EP0180921A3
公开(公告)日：1989-02-08
申请号：EP85113870.1
申请日：1985-10-31
申请人： USV PHARMACEUTICAL CORPORATION
发明人： Stevenson, David , Islam, Mohammad A.
IPC分类号： C07K1/04 , C07K1/14
CPC分类号： C07K1/02 , A61K38/00 , C07K1/067 , C07K14/585 , Y10S930/15 , Y10S930/16
摘要： Peptides, such as calcitonin, having two cysteine residues connected by a disulfide bond are prepared by a process which includes the step of cyclizing the cysteines at a pH of 8.5 to 9.0, and a concentration of 0.4 to 1.8 mg of peptide per ml of solution. These novel conditions produce rapid cyclization with an unforeseen improvement in yield.
摘要翻译：具有通过二硫键连接的两个半胱氨酸残基的肽例如降钙素通过包括以下步骤的方法制备，所述方法包括在8.5至9.0的pH下使半胱氨酸环化，并且每ml溶液的浓度为0.4至1.8mg肽。这些新颖的条件产生快速环化，产量不可预见的提高。

2. 发明公开

EP0185383A3 Bag clamping arrangement 失效
标题翻译：袋夹紧装置
公开(公告)号：EP0185383A3
公开(公告)日：1988-09-14
申请号：EP85116304
申请日：1985-12-20
申请人： USV PHARMACEUTICAL CORPORATION
发明人： Lavender, Ardis , Vrrany, George
IPC分类号： A61F05/44 , A61J01/00
CPC分类号： A61J1/16 , A61F5/44
摘要： A bag clamping arrangement, such as an arrangement for automatically controlling the filling volume and overflow of a liquid conducted into a flexible bag which is clamped in the arrangement. The bag clamping arrangement is essentially constituted of a rigid upwardly open receptacle of substantially rectangular or a relatively large upper compartment, and wherein a narrow compartment which in open communication with the upper compartment depends downwardly from the bottom of the upper compartment so as to extend longitudinally and generally centrally across the full width of the receptacle. The lower compartment includes opposite parallel sidewalls which are down so as to form a reducing compartment width therebetween. Towards the lower end of the compartment is a plate-like clamping arrangement essentially constituted of a flat plate member which may be manually engaged through an elongate slot and gripping portion proximate its upper horizontal edge. The plate member is provided along its lower edge on both sides thereof with sideways projecting resilient clamping components which, upon being inserted into the lower compartment of the receptacle, are biased towards the plate member and are dimensioned to clampingly engage between the sides of the clamping plate and the contiguous sidewalls of the lower compartment. A flexible bag is positioned on either one side, or two bags each respectively on the opposite sides of the clamping plate member prior to insertion of the latter into the receptacle, with the lower end portion of the bag or bags extending between the respective resilient clamping component and the facing surface of the clamping plate member such that, upon introduction of the clamping plate member downwardly into the lower compartment, the applicable resilient clamping component upon being biased towards the plate member, will clamp the lower bag portion against the facing surface of the clamping plate member, thereby ensuring the secure clamping of the bag.
摘要翻译：袋夹紧装置，例如用于自动控制填充体积的装置，以及被传导到柔性袋中的液体的溢出，该柔性袋被夹持在该装置中。袋夹紧装置基本上由基本为矩形或相对较大的上隔室的刚性向上开口的容器构成，并且其中与上隔室开放连通的狭窄隔室从上隔室的底部向下从顶部向下延伸，以便纵向延伸并且通常在容器的整个宽度上居中。下隔室包括向下的相对的平行侧壁，以便在它们之间形成减小隔间宽度。朝向隔室的下端是板状夹持装置，其基本上由平板构件构成，平板构件可以通过细长的槽和靠近其上部水平边缘的夹紧部分手动接合。板构件沿着其下边缘在其两侧设置有侧向突出的弹性夹紧部件，其在插入到容器的下隔室中时被朝向板构件偏置，并且被设计成夹紧地接合在夹紧件的侧面之间板和下隔室的连续侧壁。一个柔性袋在将其插入到容器中之前分别位于夹板构件的相对侧上的一侧或两个袋上，其中袋或袋的下端部分在相应的弹性夹紧夹紧板构件的面向表面和夹紧板构件的相对表面，使得当夹紧板构件向下进入下隔室时，适用的弹性夹紧构件被朝向板构件偏置时，将下袋部分夹紧在夹紧板构件，从而确保袋的牢固夹紧。

3. 发明公开

EP0127066A3 Composition for treating asthma 失效
标题翻译：用于治疗哮喘的组合物
公开(公告)号：EP0127066A3
公开(公告)日：1987-12-16
申请号：EP84105521
申请日：1984-05-15
申请人： USV PHARMACEUTICAL CORPORATION
发明人： Loev, Bernard , Brown, Richard E. , Huang, Fu-chih , Jones, Howard
IPC分类号： A61K31/42 , C07D263/58
CPC分类号： C07D263/58 , Y10S514/826
摘要： A new method of treating asthma is provided. The method is the administration of an effective dose of a Benzoxazole-2-carboxylic acid amide.
摘要翻译：提供了一种治疗哮喘的新方法。该方法是施用有效剂量的苯并恶唑-2-羧酸酰胺。

4. 发明授权

EP0051215B1 Methods and intermediates for the synthesis of 3-aryl-3-hydroxy-phthalimidines 有权
标题翻译：合成3-芳基-3-羟基 - 对羟基嘧啶的方法和中间体
公开(公告)号：EP0051215B1
公开(公告)日：1987-03-18
申请号：EP81108739.4
申请日：1981-10-22
申请人： USV PHARMACEUTICAL CORPORATION
发明人： Auerbach, Joseph , Golec, Frederick Anthony, Jr.
IPC分类号： C07D209/46 , C07D265/02
CPC分类号： C07D209/48 , C07D209/46 , C07D265/02 , Y10S514/869

5. 发明公开

EP0190722A2 Dihydro and tetrahydroquinoline derivatives 失效
标题翻译：二氢和四氢。
公开(公告)号：EP0190722A2
公开(公告)日：1986-08-13
申请号：EP86101426.4
申请日：1986-02-04
申请人： USV PHARMACEUTICAL CORPORATION
发明人： Neiss, Edward S. , Desai, Rohit M. , Youssefyeh, Raymond D.
IPC分类号： C07D215/14 , C07D215/20 , C07D215/22 , A61K31/47 , A61K31/085 , C07C33/34 , C07C43/23
CPC分类号： C07D215/233 , C07C17/093 , C07C33/34 , C07C43/23 , C07C309/00 , C07D215/14 , C07D215/20 , C07D215/60 , C07C22/04
摘要： This invention relates to novel lipoxygenase inhibitors possessing anti-inflammatory and anti-allergic activities. The present new compounds are di-and tetra-hydroquinoline or di- and tetra-hydronapthalene derivatives, more particularly, 1,2-, 1,4-, 5,6-, or 7,8-dihydro; 1,2,3,4,-tetrahydro-; 5,8-dihydro-; or 5,6,7,8-tetrahydroquinoline or napthalene derivatives of a compound of the formula:
and oxides, quaternary ammonium salts and acid salts thereof; wherein

A is CH or N;
Z is an alkylene chain containing up to 10 carbon atoms in the principal chain and a total of up to 12 carbon atoms and the said alkylene chain may be attached to the phenyl group through an oxygen atom;
R is the substituent OR 6 attached to one of the carbon atoms of Z in which R 6 is H, lower alkyl or phenyl;
X is -0(CHR 5 ) m -, alkylene of up to 2 carbon atoms in the principal chain and up to a total of 4 carbon atoms or -
-C (CHR 5 ) m -, wherein R 5 is H or CH 3 ; OH
R 1 , R 2 , R 3 , and R 4 , are each H or OH;
n' = 1 or 2; and
m = 1 or 2.

6. 发明公开

EP0189936A2 Hyposensitivity compounds 失效
标题翻译： Hyposensitiv-Verbindungen。
公开(公告)号：EP0189936A2
公开(公告)日：1986-08-06
申请号：EP86101291.2
申请日：1986-01-31
申请人： USV PHARMACEUTICAL CORPORATION
发明人： Chan, Wan-Kit , Lee, Thomas Daw-Yuan , Huang, Fu-Chih
IPC分类号： C07D209/12 , C07D209/18 , A61K31/40
CPC分类号： C07D209/12 , C07C43/23 , C07D209/18 , C07D209/22 , C07D209/26
摘要： A compound is disclosed possessing valuable pha- maceutical activity, particularly as lipoxygenase inhibitors possessing anti-inflammatory, anti-allergic properties. The compounds are of the formula:
and salts thereof; wherein

R' is independently hydrogen, alkyl, aryl, hydroxyalkyl, carboxy, carbalkoxy, carbamoyl, alkylenecarboxy, arylenecarboxy, alkylenecarbalkoxy, alkanoyl, formyl, nitrilo, amino, aminoalkylene, alkylamino, diloweralkylamino, carboxamide, halo, trihalomethyl, hydroxy, alkoxy, aralkoxy, aryloxy, nitro, sulfamoyl, mercapto, alkylthio or benzyloxy;
R 6 is alkyl, hydroxyalkyl, carboxy, aryl, carbalkoxy, carbamyl, carbalkoxy, alkanoyl, nitrilo, amino, alkylamino, diloweralkylamino, halo, trihalomethyl, aryloxy, nitro, sulfamoyl, mercapto or alkythio;
Ar is phenyl, naphthyl or a nitrogen, oxygen or sulfur containing heterocyclic or benzoheterocyclic ring;
X is alkylene containing up to 4 carbon atoms in the principal chain and up to a total of 8 carbon atoms;
R is hydrogen, alkyl or halo;
X' is oxygen, sulfur or -N(R 4 ):

Z is alkylene containing up to 10 carbon atoms in the principal chain and up to a total of 12 carbon atoms including from 0 to 2 double bonds with the proviso that when m is 0, Z may be attached to (CR=CR) n through an oxygen, sulfur or NR 4 or Z when taken together with the carbon atoms of (CR=CR) n to which it is attached may form a cycloalkylidene ring.

R is a substituent attached to one of the carbons of Z and is oxo, -OR 4 , -SR", -N(R 4 ) 2 , -COOR 4 , CHO, -CON(R 4 ) 2 , or COR 5 ;
R 3 is hydrogen, cycloalkyl, carboxy, -OR 4 , -N(R 4 ) 2 , trifluoromethyl, dialkylamino, carbalkoxy, arylaralkyl, or

R 4 is hydrogen, alkyl, benzoyl, alkanoyl, aryl or aralkyl;
m is 0 or 1;
R 6 is OR4, N(R 4 ) 2 , or H;
R' is H or R 5 ;
m' is 0 or 1;
m 2 is 0 or 1;
n is 1 or 2;
n 1 is 1, 2, or 3, except if Ar is phenyl; if Ar is phenyl, n is 1 or 3;
n 2 is 0, 1 or 2;
n 3 is 1 or 2; and
r is 0 or 1;

with the proviso that when m 2 , m 1 , r and n 2 is 0, n is 1, and R 3 is

then n is 2 and with the further proviso that when m; r, n, n 2 and n 3 are 1, m is 0 and R 2 is OR 4 , then Ar cannot be unsubstituted phenyl or hydroxyphenyl.
摘要翻译：公开了具有有价值的药物活性的化合物，特别是具有抗炎，抗过敏性质的脂氧合酶抑制剂。化合物具有下式：其中R 1独立地是氢，烷基，芳基，羟基烷基，羧基，烷氧基，氨基甲酰基，亚烷基羧基，亚芳基羧基，亚烷基烷氧基，烷酰基，甲酰基，次氮基，氨基，氨基亚烷基，烷基氨基，二低级烷基氨基，甲酰胺，卤素，三卤代甲基，羟基，烷氧基，芳烷氧基，芳氧基，硝基，氨磺酰基，巯基，烷硫基或苄氧基; R 6是烷基，羟烷基，羧基，芳基，烷基，羟基烷基，羧基，芳基，烷氧基，氨基甲酰基，烷氧基，烷酰基，次氮基，氨基，烷基氨基，二低级烷基氨基，卤素，三卤代甲基，芳氧基，硝基，氨磺酰基，巯基或炔基; Ar是苯基，萘基或氮，含硫杂环或苯并杂环; X是主链中含有最多4个碳原子并且总共8个碳原子的亚烷基; R是氢，烷基或卤素; X 1是氧，硫或 -N（R 4）; Z为亚烷基在主链中多达10个碳原子，直到总共12个碳原子，包括0至2个双键，条件是当m为0时，Z可以通过氧连接到（CR = CR）n上，硫或NR 4或Z与其所连接的（CR = CR）n的碳原子一起可以形成环烷叉环。R 2是与Z中的一个碳连接的取代基，并且是氧代， -OR 4，-SR 4，-N（R 4）2，-COOR 4，CHO，-CON（R 4）2或COR 5; R 3 >是氢，环烷基，羧基，-OR 4，-N（R 4）2，三氟甲基，二烷基氨基，烷氧羰基，芳基芳烷基或... -R-; R 4是氢，烷基，苯甲酰基，烷酰基，芳基或芳烷基; ... m为0或1; ... R 5为OR 4，N（R 4）2或H; ... R min为H或R 5; m 1为0或1; ... m 2为0或1; ... n为1或2; ... n 1为1,2或3，除非Ar为苯基; 如果Ar是苯基，n 1是1或3; ... n 2是0,1或2; ... n 3是1或2; 并且... r为0或1; ...条件是当m 2，m 1，r和n 2为0时，n为1，并且R 3为... ... -R min，......然后n 是2，进一步的条件是当m; r，n，n 2和n 3为1，m为0且R 2为OR 4，则Ar不能为未取代的苯基或羟基苯基。

7. 发明公开

EP0189142A2 Arylalkoxyphenyl-allylic alcohols as agents for the treatment of hypersensitive ailments 失效
标题翻译：芳基烷氧基苯基烯基醇孔塞米特尔Zur Behandlung einerÜberempfindlichkeitgegen Schmerzen。
公开(公告)号：EP0189142A2
公开(公告)日：1986-07-30
申请号：EP86100592.4
申请日：1986-01-17
申请人： USV PHARMACEUTICAL CORPORATION
发明人： Daw-Yuan Lee, Thomas
IPC分类号： C07C43/23 , C07C97/03 , C07C49/255 , C07C47/277 , C07C49/577 , A61K31/045 , A61K31/135 , A61K31/11 , A61K31/12
CPC分类号： C07C49/753 , C07C43/23 , C07C45/71 , C07C45/72 , C07C45/74 , C07C47/277 , C07C49/255 , C07C47/575
摘要： The present invention is concerned with the therapeutic composition comprising as an active ingredient a compound of the formula:
and salts thereof,

wherein a = 1, 2 or 3; each b = 1 or 2 and is the same value as the other;
Ar is phenyl or naphthyl containing one or two substituents selected from the group consisting of hydrogen, alkoxy, aryloxy, hydroxy, hydroxyalkyl, alkyl, aryl, halo, CF 3 , carboxy, carbalkoxy, carboxyalkoxy, carbalkoxyalkoxy, lower acyl, nitrilo, amino, nitro, mercapto or alkylthio;
Ar 1 is phenyl, naphthyl, or a nitrogen, oxygen or sulfur heterocyclic ring;
each R 1 is independently hydrogen, alkyl, carboxy, carbalkoxy, alkylenecarboxy, arylenecarboxy, alkylenecarbalkoxy, alkanoyl, formyl, nitrilo, amino, aminoalkylene, alkylamino, carboxamide, halo, trihalomethyl, hydroxy, alkoxy, aralkyloxy, aryloxy, nitro, sulfamyl, mercapto or alkylthio;
each R is H or alkyl;
Z is an alkylene chain containing up to 10 carbon atoms in the principal chain and up to a total of 12 carbon atoms and from 0 to 2 double bonds and Z when taken together with the carbon atom of (CR=CR) to which it is attached forms a cycloalkylidene ring;
each R 2 is a substituent attached to one of the carbon atoms of Z selected from the group consisting of OR 4 , SR 4 , NiH 4 ) 2 , CHO and COR 5 ;
each R 3 is H, cycloalkyl, aralkyl, aryl, lower dialkylamino, morpholino, piperazino, piperidino or CF 3 ;
each R 4 is H, alkyl, benzoyl, lower alkanoyl, aryl or aralkyl; R 5 is OR 6 or N(R 4 ) 2 ;
R 6 is H, alkyl, aryl, or aralkyl;
n = 1 or 2;
n' = 1 or 2;
n" = 1 or 2;
n"' = 1 or 2;
alkylene of up to 2 carbon atoms in the principal chain and up to a total of 4 carbon atoms, -C(R 7 ) = C(R 7 )-, -C≡C-,

m = 0 or 1;
m' = 0, 1, or 2; and
R 7 is H, CH 3 or phenyl;

wherein the group(s) designated [(R 1 ) n -Ar 1 -(X) b l a is (are) attached directly to Ar.
In addition, the present invention relates to the method of using these compounds as lipoxygenase inhibitors possessing anti-inflammatory and anti-allergic responses.
摘要翻译：本发明涉及治疗组合物，其包含作为活性成分的下式化合物及其盐，其中a = 1,2或3; 每个b = 1或2，并且与另一个相同; Ar是含有一个或两个选自氢，烷氧基，芳氧基，羟基，羟基烷基，芳基，卤素，CF 3，羧基，烷氧羰基，羧基烷氧基，碳烷氧基烷氧基，低级酰基，次氮基，氨基，硝基，巯基或烷硫基; Ar1是苯基，萘基或氮，氧或硫杂环; 每个R 1独立地是氢，烷基，羧基，烷氧基，亚烷基羧基，亚芳基羧基，亚烷基烷氧基，烷酰基，甲酰基，次氮基，氨基，氨基亚烷基，烷基氨基，甲酰胺，卤素，三卤甲基，羟基，烷氧基，芳烷氧基，芳氧基，硝基，氨基磺酰基，巯基或烷; 每个R是H或烷基; Z是主链上含有至多10个碳原子并且总共12个碳原子和0-2个双键的亚烷基链，Z与其中的（CR = CR）的碳原子一起连接形成环亚烷基环; 每个R 2是与选自OR 4，SR 4，N（R 4）2，CHO和COR 5的Z的一个碳原子连接的取代基; 每个R 3是H，环烷基，芳烷基，芳基，低级二烷基氨基，吗啉代，哌嗪基，哌啶子基或CF 3; 每个R 4是H，烷基，苯甲酰基，低级烷酰基，芳基或芳烷基; R5为OR6或N（R4）2; R6是H，烷基，芳基或芳烷基; n = 1或2; n min = 1或2; n sec = 1或2; n“'= 1或2; X = -O（CHR 7）m - ，CHCH 3 -NR 4（CHR 7）m - ，主链中最多2个碳原子的亚烷基和总共4个碳原子，-C（R 7）= C（ R 7） - ， - C≡C-，C m = 0或1; m min = 0,1或2; 且R 7为H，CH 3或苯基; 其中指定为[（R1）n1 -Ar1-（X）b] a的基团直接连接到Ar。此外，本发明涉及使用这些化合物作为具有抗炎和抗过敏反应的脂氧合酶抑制剂的方法。

8. 发明授权

EP0054936B1 Aroyl amino acids 有权
标题翻译： AROYL氨基酸
公开(公告)号：EP0054936B1
公开(公告)日：1986-06-04
申请号：EP81110594.9
申请日：1981-12-18
申请人： USV PHARMACEUTICAL CORPORATION
发明人： Suh, John Taiyoung , Menard, Paul Russell , Jones, Howard
IPC分类号： C07C153/09 , C07C149/41 , C07C103/84
CPC分类号： C07C327/00 , C07C323/00

9. 发明公开

EP0110405A3 Antiinflammatory/antiallergic compounds 有权转让
标题翻译：抗炎/抗真菌化合物
公开(公告)号：EP0110405A3
公开(公告)日：1986-05-28
申请号：EP83112031
申请日：1983-11-30
申请人： USV PHARMACEUTICAL CORPORATION
发明人： Musser, John H , Chakraborty, Utpal Ranjan
IPC分类号： C07C69/76 , C07D213/30 , C07D215/14 , C07C47/575 , C07C93/00 , C07C103/22 , C07C49/84 , C07D213/79 , C07C43/23 , C07C65/21 , C07C67/31 , C07D309/08 , C07C39/11 , C07C33/20 , C07C143/68
CPC分类号： C07D213/30 , C07C29/40 , C07C37/20 , C07C41/26 , C07C41/30 , C07C43/23 , C07C45/305 , C07C45/44 , C07C47/575 , C07C49/84 , C07C59/68 , C07C65/24 , C07C229/38 , C07C309/00 , C07D213/79 , C07D215/14 , C07C39/11 , C07C33/26
摘要： Compounds of the structure:
and pharmaceutically acceptable salts thereof, wherein R 1 and R 2 are independently hydrogen, alkyl, carboxy, alkanoyloxy, aroyloxy, carboxyalkyl, carbalkoxyalkyl, carbalkoxy, alkanoyl, formyl, nitrile, amino, aminoalkyl, alkylamino, carboxamide, halo, trihalomethyl, hydroxy, aryloxy, nitro, sulfamyl, thio, alkylthio, and R 1 and R 2 when taken together with the carbon atoms to which they are attached form a phenyl ring;
R 3 is O, OH, OR 4 , SH, SR 4 , NH, HNR 4 or N(R 4 ) 2 ; and M is an integerfrom 0 to 10; wherein Z 1 is O, S or NR 4 ; R 4 is H, alkyl, pyranyl or aryl; and R 5 is H, alkyl orfluoro.

10. 发明公开

EP0178381A2 Phenylacetamides as anti-allergy, anti-asthma and anti-inflammatory agents 失效
标题翻译：苯乙酰胺als抗过敏，抗哮喘和antiphlogistische Mittel。
公开(公告)号：EP0178381A2
公开(公告)日：1986-04-23
申请号：EP85106617.5
申请日：1985-05-29
申请人： USV PHARMACEUTICAL CORPORATION
发明人： Stevenson, David , Liu, Robert C. , Ho, Laurence L. , Jones, Howard , Coutts, Stephen
IPC分类号： C07C103/76 , C07C149/243 , C07D209/20 , A61K31/165 , A61K31/195 , A61K31/215 , A61K31/40
CPC分类号： C07D209/20
摘要： Compounds of the structure:
and pharmaceutically acceptable salts thereof, wherein

R 7 is H or halogen;
R, and R 2 are independently OH, lower alkyl, lower alkoxy, aryloxy, heteroaryloxy, heteroaryl lower alkoxy, aryl, heteroaryl, aryl lower alkyl, aryl lower alkoxy, halogenated aryl lower alkoxy, lower alkenyl, lower alkynyl, lower alkenoxy, lower alkynoxy, halogen, trifluoromethyl, cyclopropy-Imethoxy or cyclohexenoxy;
A is H, aryl, lower alkyl, aryl lower alkyl or heteroaryl; and
B is
or

is an amino acid, N-lower alkyl amino acid, N-aryl lower alkyl amino acid or N-heteroaryl amino acid, or lower alkyl esters or amides thereof;
n = 0-6;

M is H, lower alkyl, or CH 2 OR 5 ;
R 5 is H, lower alkyl, aryl, aryl lower alkyl or heteroaryl;
R 6 is lower alkyl, aryl, aryl lower alkyl or heteroaryl;
E is OH, lower alkyl, aryl or heteroaryl;
F is
and
G is OH, lower alkyl, lower alkoxy, aryloxy, heteroaryl, aryl lower alkyl, aryl lower alkoxy, halogenated aryl lower alko xy, lower alkenyl, lower alkynyl, lower alkenoxy, lower alkynoxy, halogen or trifluoromethyl.
摘要翻译：结构化合物及其药学上可接受的盐，其中：R 1和R 2独立地为H，OH，低级烷基，低级烷氧基，芳氧基，杂芳氧基，杂芳基低级烷氧基，芳基，杂芳基，芳基 - 低级烷基，烷氧基，卤代芳基 - 低级烷氧基，低级烯基，低级炔基，低级链烯氧基，低级炔氧基，卤素或三氟甲基; A是H，芳基，低级烷基，芳基 - 低级烷基或杂芳基; 并且B是N = 0-6，其中D是H，CONR 3 R 4，CO 2 H，CO 2 R 5，CH 2 OH或CH 2 OR 6，其中R 3，R 4，R 5和R 6独立地是H，低级烷基，芳基，芳基 - 低级烷基或杂芳基 ; E是H，OH，低级烷基，芳基或杂芳基; 且F为，其中G与R1和R2相同，可用于治疗过敏，哮喘和炎性病症。

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