Aprotinin
(Synonyms: 抑肽酶) 目录号 : GC12900
抑肽酶是一种天然存在的丝氨酸蛋白酶抑制剂，可挽救生命并降低中风和因大量出血而重复手术的风险1, 2, 3。
Cas No.:9087-70-1
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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Potency：6115U/mg (dried product)
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment: [1] | |
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Cell lines |
HUVEC cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
1600 kIU/mL, 60 min |
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Applications |
Aprotinin dose-dependently inhibited the TNF-α–induced expression of ICAM-1 and VCAM-1, but not E-selectin. |
| Animal experiment : [2] | |
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Animal models |
3- to 4-mo-old male Albino Wistar rats |
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Dosage form |
The rats were anesthetized by 50 mg/kg of ketamine initially and treated with 12 mmHg pneumoperitoneum for 4h. Additional lower doses of ketamine were administered i.p. until the end of pneumoperitoneum to maintain anesthesia. A loading aprotinin dose of 28000 KIU/kg was given i.p. after the onset of pneumoperitoneum, followed by lower maintenance doses (7500 KIU/kg), which were administered per hour until the termination. Splanchnic reperfusion period lasted 60 or 180 min. |
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Applications |
Treatment of aprotinin caused reduction of several cytokines and markers (TNF-α, IL-6, endothelin 1, C reactive protein, PAB and carbonyl proteins) of oxidative stress in all tissues (liver, small intestine, and lung) studied. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Asimakopoulos G, Lidington E A, Mason J, et al. Effect of aprotinin on endothelial cell activation. The Journal of thoracic and cardiovascular surgery, 2001, 122(1): 123-128. [2] Baltatzis M, Pavlidis T E, Ouroumidis O, et al. Aprotinin reduces oxidative stress induced by pneumoperitoneum in rats. Journal of Surgical Research, 2014, 189(2): 238-248. |
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Aprotinin, a naturally occurring serine protease inhibitor, saves lives and decreases the risk of stroke and repeat surgery for massive bleeding1, 2, 3.
The use of aprotinin did not significantly increase the risk of renal failure or the need for postoperative renal replacement despite an increase in the proportion of patients who had a doubling of serum creatinine levels. The adjudication of death did not identify renal failure as contributing to or causing death associated with aprotinin use. A Meta analysis by Brown and colleagues showed a nonsignificant relative risk of renal failure with high-dose aprotinin4.
Although aprotinin is potentially more effective than other active agents in controlling hemostasis, we noted only a possible trend suggesting that it decreased massive bleeding. Only repeat surgeries and important blood losses through chest tubes, one of the main indications for surgery, were potentially improved by the use of aprotinin. Aprotinin did not appear to prevent massive bleeding or save the life of patients who had massive bleeding.
The adverse effects on mortality associated with aprotinin may also have been present among healthier patients, those under the age of 65 years, and those without coexisting illnesses at the time of surgery.
Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative mortality trend associated with aprotinin as compared with lysine analogues precludes its use in patients undergoing high-risk cardiac surgery5.
Reference:
1.Henry DA, Carless PA, Moxey AJ, et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2007;4:CD001886.
2.Levi M, Cromheecke ME, de Jonge E, et al. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet 1999;354:1940-7.
3.Sedrakyan A, Treasure T, Elefteriades JA. Effect of aprotinin on clinical outcomes in coronary artery bypass graft surgery: a systematic review and meta-analysis of randomized clinical trials. J Thorac Cardiovasc Surg 2004;128:442-8.
4.Brown JR, Birkmeyer NJ, O’Connor GT. Meta-analysis comparing the effectiveness and adverse outcomes of antifibrinolytic agents in cardiac surgery. Circulation 2007;115:2801-13.
5.Dean A. Fergusson, Paul C. Hébert et al, A Comparison of Aprotinin and Lysine Analogues in High-Risk Cardiac Surgery, N Engl J Med 2008; 358:2319-2331
抑肽酶是一种天然存在的丝氨酸蛋白酶抑制剂,可挽救生命并降低中风和因大量出血而重复手术的风险1, 2, 3。
尽管血清肌酐水平加倍的患者比例增加,但抑肽酶的使用并未显着增加肾功能衰竭或术后肾脏置换需求的风险。死亡裁定并未将肾功能衰竭确定为促成或导致与抑肽酶使用相关的死亡。 Brown 及其同事的一项荟萃分析显示,大剂量抑肽酶4 的肾衰竭相对风险不显着。
虽然抑肽酶在控制止血方面可能比其他活性药物更有效,但我们只注意到一个可能的趋势表明它可以减少大出血。只有重复手术和通过胸管大量失血（手术的主要适应症之一）才可能通过使用抑肽酶得到改善。抑肽酶似乎不能预防大出血或挽救大出血患者的生命。
抑肽酶对死亡率的不利影响也可能存在于更健康的患者、65 岁以下的患者以及手术时没有合并症的患者中。
尽管与赖氨酸类似物相比,抑肽酶可能会适度降低大出血的风险,但其强烈且一致的负死亡率趋势阻碍了其在接受高风险心脏手术的患者中的使用5.
| Cas No. | 9087-70-1 | SDF | |
| 别名 | 抑肽酶 | ||
| Canonical SMILES | CC(O)=O.CC.CC.CCccC.[R].[P].[2H].[L].[E].[P].[P].[Y].[3H].[G].[KH].[R].[R].[Y].F.[Y].[*].[L].F.[V].[Y].[G].[G].[R].[KH].[R].N.N.F.[KH].S.[*].[2H].[R].[G].[G].[*].[KH].[*].[3H].C.[*].F.[P].[*].I.I.N.[Q].[3H].[M] | ||
| 分子式 | C284H432N84O79S7 | 分子量 | 6511.44 |
| 溶解度 | ≥ 195mg/mL in Water | 储存条件 | Store at 2-8°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 | 0.1536 mL | 0.7679 mL | 1.5358 mL |
| 5 mM | 0.0307 mL | 0.1536 mL | 0.3072 mL |
| 10 mM | 0.0154 mL | 0.0768 mL | 0.1536 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。
Aprotinin
Ann Pharmacother 1996 Apr;30(4):372-80.8729892 10.1177/106002809603000410
Objective: To review the clinical pharmacology of Aprotinin in patients undergoing surgical procedures involving major blood loss, namely, coronary artery bypass graft (CABG). Data sources: A MEDLINE search was used to identify French- and English-language publications on Aprotinin using the indexing terms Aprotinin, cardiothoracic surgery, and hemorrhage. The MEDLINE search was supplemented by review of article bibliographies. Data also were obtained from the approved Canadian and US product labels. Study selections: All abstracts and uncontrolled and controlled clinical trials were reviewed. Data extraction: Study design, population, results, and safety information were retained. Efficacy conclusions were drawn from controlled trials. Data synthesis: Aprotinin, a serine protease inhibitor isolated from bovine lung tissue, decreases bleeding after cardiac surgery by mechanisms including antifibrinolytic activity and preservation of platelet function. Several trials have shown that Aprotinin reduced blood loss and transfusion requirements in patients undergoing CABG. Its use in other surgical procedures involving major blood loss has been reported. Aprotinin is well tolerated, with minor allergic reactions being the most frequently reported adverse effect. Although unsubstantiated, the possibility that Aprotinin could create a prothrombic state leading to early graft occlusion and formation of microthrombi in renal and coronary vasculatures is of concern. Conclusions: Aprotinin is an effective hemostatic agent in CABG. Clear definitions of indications, dosing, safety, and repeated use remain to be investigated thoroughly.
Aprotinin
Int Anesthesiol Clin 2004 Fall;42(4):81-91.15577702 10.1097/00004311-200404240-00009
Aprotinin in perspective
Ann Thorac Surg 1993 Apr;55(4):1033-41.7682054 10.1016/0003-4975(93)90149-c
Aprotinin is a nonspecific serine protease inhibitor extracted from bovine lung. It was first used during cardiopulmonary bypass to inhibit plasmin-induced complement activation. By chance significant reductions of blood loss and blood requirements were noted in treated patients. Subsequent investigation showed improved hemostasis to result from protection of platelet adhesive receptors (Gp Ib) at the onset of cardiopulmonary bypass. Without Aprotinin the contact system of plasma is massively activated on first passage through the cardiopulmonary bypass circuit. Activation of the intrinsic coagulation pathway causes thrombin formation, which impairs platelet adhesive function. Aprotinin blocks contact activation of the kallikrein system during cardiopulmonary bypass and in synergy with heparin prevents thrombin formation through inhibition of the intrinsic clotting cascade. It is likely that neither thrombin nor platelets become involved in the blood-foreign surface contact activation process in aprotinin-treated patients. The fact that the hemostatic process is affected from the very beginning of cardiopulmonary bypass is substantiated by the fact that low-dose Aprotinin therapy (2 x 10(6) KIU Aprotinin added to the pump prime) leads to the same preservative effect on Gp Ib receptors and blood loss as continuous high-dose infusion (6 x 10(6) KIU) throughout the whole surgical procedure. In the presence of heparin Aprotinin prolongs the activated clotting time and the in vitro activated partial thromboplastin time. This has important implications for heparin dosage. An inhibitory effect on the endothelial cell anticoagulant function may also have consequences during hypothermic low flow and circulatory arrest states.(ABSTRACT TRUNCATED AT 250 WORDS)
Aprotinin: 1 year on
Curr Opin Anaesthesiol 2009 Feb;22(1):121-7.19295302 10.1097/ACO.0b013e32831c833f
Purpose of review: The nonspecific protease inhibitor Aprotinin has been used successfully to reduce bleeding in cardiac surgery. Recent investigations have questioned its safety, and Aprotinin has finally been withdrawn from marketing after a large prospective study demonstrated a trend toward higher mortality. Recent findings: The initial studies of Karkouti and Mangano provoked a considerable number of large-scale investigations focusing on the safety issues of Aprotinin. These studies were of retrospective nature and used sophisticated statistical methods to overcome a possible selection bias. Recently, Aprotinin was predominantly used in patients with a higher risk of bleeding, which hampers a retrospective comparison with patients without the drug. This review summarizes the diverging results of these studies. Summary: It remains a matter of speculation whether the quality and results of published data justify the withdrawal of Aprotinin; however, one has to accept that this drug is no longer available. It is clear from the Aprotinin story that there are no effective instruments to control the safety and clinical efficacy of a drug after its regulatory approval. This highlights the urgent need for independent clinical safety studies after the formal registration of a drug.
Aprotinin in cardiac surgery
Expert Rev Cardiovasc Ther 2006 Mar;4(2):151-60.16509811 10.1586/14779072.4.2.151
Aprotinin is a naturally occurring serine protease inhibitor that is being used with increasing frequency in cardiac surgery and beyond to reduce blood loss and the need for perioperative blood transfusion. Through inhibition of serine proteases such as plasmin, Aprotinin significantly reduces fibrinolysis, thereby aiding hemostasis during surgical procedures. In addition, Aprotinin interacts with other factors in the coagulation and fibrinolytic cascade, creating a hemostatic balance, without increasing the risk of thrombosis. These proven benefits are supplemented by the anti-inflammatory properties of Aprotinin, which may help curb some of the deleterious effects of cardiopulmonary bypass. This article will review the discovery of Aprotinin, its mechanism of action, dosing and adverse effects, and highlight the major recent trials demonstrating its efficacy.