Inogatran (H-314-27)
(Synonyms: 伊诺加群; H-314-27) 目录号 : GC32554
Inogatran (H-314-27) (H-314-27) 是一种合成凝血酶抑制剂，用于治疗和预防动脉和静脉血栓性疾病。
Cas No.:155415-08-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Inogatran is a synthetic thrombin inhibitor, developed for the possible treatment and prophylaxis of arterial and venous thrombotic diseases.
Inogatran (0.075, 0.25, 0.75 mg/kg, i.v.) results in dose-dependent increases in activated partial thromboplastin time (aPTT), thrombin time (TT), and prothrombin time (PT) in a canine electrolytic injury model of venous thrombosis[1]. Inogatran dose-dependently inhibits thrombus formation, which is measured as an increase in time to occlusion (TTO) and a decrease in thrombus weight. Inogatran also improves vena caval blood flow and reduces the overall incidence of thrombotic occlusion in a rat model[2].
[1]. Ignasiak DP, et al. Effects of Intravenous Enoxaparin and Intravenous Inogatran in an Electrolytic Injury Model of Venous Thrombosis in the Dog. J Thromb Thrombolysis. 1998 Nov;6(3):199-206. [2]. Chi L, et al. Antithrombotic effect of LB-30057 (CI-1028), a new synthetic thrombin inhibitor, in a rabbit model of thrombosis: comparison with inogatran. J Thromb Thrombolysis. 2001 Feb;11(1):19-31.
| Cas No. | 155415-08-0 | SDF | |
| 别名 | 伊诺加群; H-314-27 | ||
| Canonical SMILES | O=C(O)CN[C@H](CC1CCCCC1)C(N2[C@H](C(NCCCNC(N)=N)=O)CCCC2)=O | ||
| 分子式 | C21H38N6O4 | 分子量 | 438.56 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2802 mL | 11.4009 mL | 22.8019 mL |
| 5 mM | 0.456 mL | 2.2802 mL | 4.5604 mL |
| 10 mM | 0.228 mL | 1.1401 mL | 2.2802 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Antithrombotic activity of Inogatran, a new low-molecular-weight inhibitor of thrombin, in a closed-chest porcine model of coronary artery thrombosis
Cardiovasc Res 1996 Aug;32(2):320-7.PMID:8796119DOI:10.1016/0008-6363(96)00114-9.
Objective: To characterize the antithrombotic activity of Inogatran per se in a porcine model of copper-coil-induced coronary artery thrombosis and to compare its effect with that of heparin and ASA. Methods: Forty-eight pigs were assigned to one of the following groups: (1) saline; (2) heparin, (a) 75 and (b) 150 IU/kg/h; (3) acetylsalicylic acid (ASA), 12.5 mg/kg; (4) ASA 12.5 mg/kg + Inogatran, 0.06 mg/kg/h; (5) ASA 12.5 mg/kg + Inogatran, 0.30 mg/kg/h; (6) Inogatran, 0.30 mg/kg/h; (7) Inogatran, 0.60 mg/kg/h; (8) Inogatran, 1.5 mg/kg/h. Computerized vectorcardiography was applied to monitor coronary occlusion and reperfusion. Results: Cumulative time in which coronary arteries were patent, expressed as a percentage of the treatment time (i.e., 90 min) in heparin- and ASA-treated pigs, was 8 +/- 6 and 14 +/- 7%, respectively. This is not significantly different from placebo-treated pigs. Inogatran-treated pigs showed a dose-dependent antithrombotic effect, and the average patency rates were 34 +/- 39, 54 +/- 37 and 80 +/- 32%, in groups 6, 7 and 8, respectively. Combined treatment with Inogatran and ASA did not significantly improve the antithrombotic effect. A partial antithrombotic effect of Inogatran was maintained for, on average, at least 150 min after the end of treatment, as evidenced by patency rates of 31 +/- 43, 52 +/- 48 and 62% +/- 44, in groups 6, 7, and 8, respectively. Conclusion: Inogatran inhibits the formation of arterial thrombosis more effectively than heparin or ASA. Inhibition of clot-bound thrombin and thrombin-induced platelet activation may be the mechanisms behind this effect. Our findings also suggest that a thrombus formed in the presence of Inogatran is more susceptible to spontaneous endogenous fibrinolysis.
Activated partial thromboplastin time and clinical outcome after thrombin inhibition in unstable coronary artery disease
Eur Heart J 1999 Nov;20(22):1657-66.PMID:10543929DOI:10.1053/euhj.1999.1750.
Aims Direct thrombin inhibitors have failed to prove superiority over unfractionated heparin in several clinical trials of unstable coronary artery disease. We have investigated the relationship between activated partial thromboplastin time levels and adverse clinical events, i.e. death, myocardial (re-)infarction or refractory angina. Methods and Results One thousand two hundred and nine patients with unstable coronary artery disease were randomized to 72 h infusion with Inogatran, a low molecular mass direct thrombin inhibitor, or unfractionated heparin. During 30 days follow-up there was no significant difference between Inogatran and unfractionated heparin treatment as regards clinical outcome. 11.6% of the 464 Inogatran treated patients with activated partial thromboplastin time above the median at 6 h (44 s) had a clinical event in 7 days, and 6.6% of the 423 patients with activated partial thromboplastin time below the median (P=0.01). After 30 days the event rate was still 41% higher in the Inogatran patients with activated partial thromboplastin time above the median (P=0.06). Activated partial thromboplastin time in quartiles indicated a direct relationship between higher activated partial thromboplastin time and worse outcome. In contrast, during heparin infusion there was a trend for improved clinical outcome with activated partial thromboplastin time above the median, but this benefit was lost after cessation of treatment. Conclusions: Higher activated partial thromboplastin time levels during Inogatran treatment are related to increased risk of death, myocardial infarction or refractory angina. This might, at least in part, be explained by differences in anticoagulant mechanisms between direct thrombin inhibitors and heparin, and further emphasizes the poorly defined optimal activated partial thromboplastin time range during treatment with direct thrombin inhibitors in unstable coronary artery disease.
Thrombin inhibition with Inogatran for unstable angina pectoris: evidence for reactivated ischaemia after cessation of short-term treatment
Coron Artery Dis 1996 Sep;7(9):673-81.PMID:8950498DOI:10.1097/00019501-199609000-00009.
Background: The acute coronary syndromes of unstable angina and non-Q-wave infarction are initiated by coronary plaque rupture and subsequent thrombus formation. Thrombin is central to this response as it activates platelets and the coagulation system. In an open design study we assessed the tolerability and safety of the low molecular weight thrombin inhibitor, Inogatran, for unstable angina or non-Q-wave infarction. Methods: Thirty-seven patients, treated within 72 h of symptoms, were allocated consecutively to groups to receive a 4 h infusion with one of three doses of Inogatran. Thrombin generation and activity were measured with plasma markers at baseline, after the 4 h treatment period and 4 h later. Ischaemia was monitored using continuous vectorcardiography during the 4 h of treatment and during the subsequent 4 h after Inogatran infusion had been stopped, to detect any increase in ischaemic events after the period of treatment. In addition, 12 patients received Inogatran as an infusion for 72 h. Results: Inogatran was tolerated well. There were no adverse haemodynamic effects or allergic reactions. Minor bleeding events were detected in 37% of the patients. The biochemical and vectorcardiographic findings indicated suppression of thrombin generation after the 4 h treatment period compared with baseline. During the first 4 h after Inogatran treatment, thrombin activity and episodes of ischaemia were increased compared with during the treatment period. Conclusion: Inogatran was tolerated well and was safe, but its discontinuation was followed by a reactivation of thrombin activity and ischaemia. Whether this reactivation represented a rebound phenomenon, or merely resulted from the discontinuation of an effective therapy, cannot be established from the present study.
Inhibition of binding of an enzymatically stable thrombin inhibitor to lumenal proteases as an additional mechanism of intestinal absorption enhancement
Pharm Res 1999 Jan;16(1):74-9.PMID:9950282DOI:10.1023/a:1018870712463.
Purpose: The objective of the study was to investigate the mechanisms behind increased bioavailability of an enzymatically stable thrombin inhibitor, Inogatran, after coadministration with a trypsin inhibitor, aprotinin. Methods: Rat jejunum, ileum and colon segments were stripped and mounted in modified Ussing chambers, and the permeability to Inogatran was determined both in the presence and absence of aprotinin. Inogatran and aprotinin were also coadministered intraduodenally to conscious rats. Competitive binding of Inogatran to trypsin was studied using kinetic dialysis and was compared to aprotinin. The fraction of free (unbound) trypsin probe, in the absence of trypsin inhibitors was determined by performing experiments without pancreatine and without inhibitors, respectively. Results: A 3-fold increased permeability to Inogatran in the presence of aprotinin was seen in vitro, in some cases correlated with changed barrier properties of the intestinal segments. The in vitro results were well correlated with the in vivo results. There was a 5-fold increase in the bioavailability of Inogatran in the presence of aprotinin. The binding of a trypsin probe was inhibited by both the presence of Inogatran and aprotinin. Aprotinin showed a several fold higher displacement than Inogatran. The results indicate both an effect of aprotinin on the epithelial membrane and an inhibition of binding of the thrombin inhibitor to trypsin or other serine proteases in the gut. Conclusions: The coadministration of aprotinin with enzymatically stable peptides, like thrombin inhibitors, may improve their absorption after oral administration. This suggests a new additional mechanism for intestinal absorption enhancement of peptide drugs.
The effect of a low molecular mass thrombin inhibitor, Inogatran, and heparin on thrombin generation and fibrin turnover in patients with unstable coronary artery disease
Eur Heart J 1999 Apr;20(7):506-18.PMID:10365287DOI:10.1053/euhj.1998.1336.
Aim: This study evaluated a novel specific thrombin inhibitor, Inogatran, in comparison with unfractionated heparin, with regard to markers for coagulation activity in patients with unstable coronary artery disease. Methods and results: In the Thrombin Inhibition In Myocardial Ischaemia (TRIM) study patients were randomized to one of three different doses of Inogatran or to unfractionated heparin, given intravenously over 72 h. In a subpopulation of 320 patients, markers for coagulation activity were measured at baseline, during and after the study infusion. Prothrombin fragment 1 + 2, indicating thrombin generation, decreased in the low, medium and high dose Inogatran groups and in the heparin group during the first 6 h of treatment by 12%, 15%, 21% and 26%, respectively. From 6 h to 72 h after the start of infusion the levels changed by -7%, -6%, -4% and +34%, respectively. The increase in the heparin group continued after the infusion was stopped. Thrombin-antithrombin complex, also indicating thrombin generation, decreased by 0%, 2%, 18% and 22%, respectively, during the first 6 h of treatment. During the same period soluble fibrin, an intermediate in fibrin formation, increased both in the low and medium Inogatran group by 9%, while a decrease by 4% and 18%, respectively, was seen in the high dose Inogatran group and in the heparin group. Fibrin dissolution, as measured by fibrin D-dimer, decreased during the first 24 h of treatment by 20%, 18%, 18% and 20%, respectively. The first 24 h after discontinuation of infusion, fibrin D-dimer increased by 6%, 23%, 25% and 44%, respectively. After 72 h, at the end of infusion, patients treated with Inogatran, to a larger extent than those given heparin, had suffered from death, myocardial infarction or refractory angina pectoris. After 7 days this trend was less marked. Conclusion: The more pronounced decrease in thrombin generation and fibrin turnover during the first 6 h of infusion, and the later increase in thrombin generation and fibrin turnover, in the heparin group, as compared to the Inogatran groups, may be related to the lower clinical event rate during infusion with heparin compared with Inogatran and the recurrence of ischaemic events, early after cessation of heparin infusion.