磺达肝癸钠说明方案

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【免费下载】磺达肝癸钠说明书

磺达肝癸钠说明书基本信息编辑辅料：氯化钠，注射用水，盐酸，氢氧化钠。

本品为无色澄明液体。

本品预灌式一次性使用注射器由I型玻璃管(1mL)和附着的一个27规格x12.7mm的针头组成，并配有溴丁基或氯丁基弹性活塞。

【适应症】3用法用量编辑进行重大骨科手术的患者：本品推荐剂量为每日1次2.5mg，术后皮下注射给药。

初始剂量应在手术结束后6小时给予，并且需在确认已止血的情况下。

治疗应持续到静脉血栓栓塞风险消失以后，通常到患者可以下床活动，至少在手术后5-9天。

临床经验显示：进行髋关节骨折手术的患者，发生静脉血栓栓塞的危险将持续至手术后9天以上。

对于这些患者，应考虑将本品的使用时间再延长24天。

特殊群体：在进行重大骨科手术的患者中，对于那些年龄大于75岁、和/或体重低于50kg、和/或肌酐清除率为20-50mL/min的肾脏损害患者，应严格遵循本品的首次注射时间。

本品首次给予应不早于手术结束后6小时。

除非术后已经止血，否则不应注射本品。

肾功能损害：肌酐清除率<20mL/min的患者不应使用本品。

肌酐清除率在20-30mL/min范围内的肾脏损害患者，本品推荐剂量为1.5mg。

对于肌酐清除率在30-50mL/min范围内的肾脏损害患者，根据药代动力学模拟结果可以考虑使用本品1.5mg剂量进行短期预防。

对于长期预防本品1.5mg剂量应被作为替代2.5mg的用量。

肝功能损害：不需要调节剂量。

在严重肝功能损害的患者中，本品应谨慎使用。

儿科：在<17岁的人群中本品的疗效和安全性未经研究。

使用方法：本品是通过皮下深层注射给予的，患者取卧位。

注射部位应该在前侧和后侧腹壁之间左右交替。

为了避免药物的丢失，当使用预灌式注射器时，注射前不要排除注射器中的气泡。

注射针的全长应垂直插入拇指和食指之间的皮肤皱褶内；整个注射过程中应始终保持有皮肤皱褶。

见【用药须知】中使用、处理和处置指导的相关内容。

【药物过量】本品使用推荐剂量以上的剂量可能导致出血风险的增加。

安卓(磺达肝癸钠注射液)

安卓(磺达肝癸钠注射液)【药品名称】商品名称：安卓通用名称：磺达肝癸钠注射液英文名称：Fondaparinux Sodium Injection【成份】磺达肝癸钠FondaparinuxNa【适应症】本品用于进行下肢重大骨科手术如髋关节骨折、重大膝关节手术或者髋关节置换术等患者，预防静脉血栓栓塞事件的发生。

【用法用量】进行重大骨科手术的患者：本品推荐剂量为每日1次2.5mg，术后皮下注射给药。

初始剂量应在手术结束后6小时给予，并且需在确认已止血的情况下。

治疗应持续到静脉血栓栓塞风险消失以后，通常到患者可以下床活动，至少在手术后5-9天。

临床经验显示：进行髋关节骨折手术的患者，发生静脉血栓栓塞的危险将持续至手术后9天以上。

对于这些患者，应考虑将本品的使用时间再延长24天。

本品首次给予应不早于手术结束后6小时。

除非术后已经止血，否则不应注射本品。

肾功能损害：肌酐清除率【不良反应】对本品2.5mg剂量的安全性进行了评价，其中3595位进行重大下肢骨科手术的患者治疗使用时间达9天；327位进行髋关节骨折手术的患者，经过初始1周的预防治疗后再给予3周的治疗；1407位进行腹部手术的患者治疗达9天；以及425位具有血栓栓塞并发症风险的内科患者中治疗达到14天。

研究者报道的、至少与本品可能有关的不良反应见下列频次分组(常见：ge；1%，lt；10%；不常见：ge；0.1%，lt；1%；罕见：ge；0.01%，lt；0.1%)；以及根据严重程度依次降低的次序进行的全身器官分类；这些不良反应应【禁忌】下列情况禁用本品：已知对磺达肝癸钠或本品中任何赋形剂成分过敏；具有临床意义的活动性出血；急性细菌性心内膜炎；肌酐清除率【注意事项】本品仅用于皮下注射。

《磺达肝癸钠》课件

剂型改进
为了提高药物的疗效和方便患者使用，未来磺达肝癸钠的剂型可能会得到改进，如开发出长效剂型、口服剂型等。
联合用药
磺达肝癸钠可能与其他药物联合使用，以提高疗效或降低不良反应，未来的研究将进一步探索其与其他药物的联合应用。
与其他药物的比较研究
磺达肝癸钠与低分子量肝素的比较
磺达肝癸钠作为新型抗凝药物，与低分子量肝素相比具有更好的疗效和安全性，未来将进一步比较两者的优劣。
药动学
01
02
03
04
吸收
磺达肝癸钠口服吸收迅速，生物利用度高。
分布
磺达肝癸钠在体内分布广泛，主要分布在血液、肝脏和肾脏
。
代谢
磺达肝癸钠主要通过肝脏代谢，代谢产物主要经肾脏排泄。
排泄
磺达肝癸钠的排泄速度较慢，半衰期较长，可达到20小时
以上。
药物相互作用
1 2
与抗血小板药物的相互作用
磺达肝癸钠与抗血小板药物如阿司匹林、氯吡格雷等合用时，应密切监测出血风险。
与溶栓药物的相互作用
磺达肝癸钠与溶栓药物如尿激酶、链激酶等合用时，应谨慎使用，避免出血并发症。
3
与非甾体抗炎药物的相互作用
非甾体抗炎药物如布洛芬、吲哚美辛等可增强磺达肝癸钠的抗凝作用，合用时应谨慎。
PART 03
磺达肝癸钠的临床应用
REPORTING
适应症
急性冠脉综合征
磺达肝癸钠主要用于接受PCI术的急性冠脉综合征患者，以降低血栓形成的风险。
在磺达肝癸钠的临床试验中，通常会采用随机对照试验（RCT）的方法，将受试者随机分为试验组和对照组Biblioteka 以消除偏差和偏见。疗效评价
疗效评价是对药物疗效的评估，通常采用客观的指标进行评价，如生存率、缓解率、症状改善率等。

磺达肝癸钠原料药USP38标准

Chromatographic systemAdd the following:(See Chromatography 〈621〉, System Suitability .)Mode: LCDetector: UV 254 nmvFondaparinux SodiumColumn: 4.6-mm × 25-cm; packing L1Flow rate: 1mL/min Injection size: 25µLSystem suitabilitySamples: System suitability solution and Standard solutionSuitability requirementsResolution: NLT 3.6 between folic acid related com-pound A (calcium formyltetrahydrofolate) and folic acid, System suitability solutionRelative standard deviation: NMT 2.0%, Standard solution C 31H 43N 3O 49S 8Na 101728.08Analysisα-D -Glucopyranoside, methyl O -2-deoxy-6-O -sulfo-Samples: Standard solution and Sample solution 2-(sulfoamino)-α-D -glucopyranosyl-(1→4)-O -β-D -Calculate the percentage of the labeled amount ofglucopyranuronosyl-(1→4)-O -2-deoxy-3,6-di-O -sulfo-folic acid (C 19H 19N 7O 6) in the portion of Tablets taken:2-(sulfoamino)-α-D -glucopyranosyl-(1→4)-O -2-O -sulfo-α-L -Result = (r U /r S ) × (C S /C U ) × 100idopyranuronosyl-(1→4)-2-deoxy-2-(sulfoamino)-, 6-(hy-drogen sulfate), decasodium salt;r U= peak area of folic acid from the SampleMethyl O -2-deoxy-6-O -sulfo-2-(sulfoamino)-α-D -glucopyra-solutionnosyl-(1→4)-O -β-D -glucopyranuronosyl-(1→4)-O -2-deoxy-r S = peak area of folic acid from the Standard3,6-di-O -sulfo-2-(sulfoamino)-α-D -glucopyranosyl-(1→4)-O -solution2-O -sulfo-α-L -idopyranuronosyl-(1→4)-2-deoxy-6-O -sulfo-C S = concentration of USP Folic Acid RS in the2-(sulfoamino)-α-D -glucopyranoside, decasodium salt Standard solution (mg/mL)[114870-03-0].C U = nominal concentration of folic acid in theDEFINITIONSample solution (mg/mL)Fondaparinux Sodium is the sodium salt of a syntheticAcceptance criteria: 90.0%–115.0%sulfated pentasaccharide anticoagulant based on the anti-PERFORMANCE TESTS thrombin binding moiety of heparin. It is synthesized •D ISSOLUTION 〈711〉from a natural source of chirally pure sugars (mono- and Medium: Water; 500mL di-saccharides). A range of coupling, (de)protection and Apparatus 2: 50 rpm functionalization reactions leads to crude fondaparinux so-Time: 45 mindium, which is further purified to yield the drug sub-Standard solution: Solution having a known concentra-stance. Fondaparinux Sodium contains NLT 95.0% and tion of USP Folic Acid RS, corrected for water content,NMT 103.0% of fondaparinux sodium, calculated on the in Mediumanhydrous and solvent-free basis. Fondaparinux Sodium is Sample solution: Filtered portion of the solution under a white to off-white powder.test, suitably diluted with the Medium if necessary IDENTIFICATIONAnalysis•A . 13C NMR S PECTRUMSamples: Standard solution and Sample solutionNMR reference: Dissolve in 1mL of deuterium oxide Proceed as directed in the Assay , making any necessary 20mg of (2,2,3,3-(d4)-3-(trimethylsilyl)propionic acid modifications.sodium salt (TSP), enriched to 98% deuterated or Calculate the percentage of the labeled amount of equivalent, as a chemical shift reference.folic acid (C 19H 19N 7O 6) dissolved:Standard solution: NLT 40mg/mL of USPResult = (r U /r S ) × (C S × D × V /L ) × 100Fondaparinux Sodium Identification RS in deuterium oxider U= peak area of folic acid from the SampleSample solution: NLT 40mg/mL of Fondaparinux So-solutiondium in deuterium oxide r S = peak area of folic acid from the StandardInstrumental conditionssolution(See Nuclear Magnetic Resonance 〈761〉.)C S = concentration of USP Folic Acid RS in theMode: NMR, pulsed (Fourier transform)Standard solution (mg/mL)Frequency: NLT 100MHz (for 13C)D = dilution factor for the Sample solution Temperature: 40°V = volume of Medium , 500mL System suitabilityL = label claim (mg/Tablet)Sample: Standard solutionTolerances: NLT 75% (Q ) of the labeled amount of folic Using a pulsed (Fourier transform) NMR spectrometer acid (C 19H 19N 7O 6) is dissolved.operating at NLT 100MHz for 13C, acquire a free in-•U NIFORMITY OF D OSAGE U NITS 〈905〉: Meet the duction decay (FID) using a 90° pulse and a 5-s delay.requirements Record the 13C NMR spectra of the NMR reference at 40°, and set the trimethylsilyl resonance to 0.0ppm.ADDITIONAL REQUIREMENTSCollect the 13C NMR spectrum with a spectral window •P ACKAGING AND S TORAGE : Preserve in well-closed of at least 235 to −10ppm with spinning at 20 Hz,containers.using line broadening of NLT 1. The number of tran-•USP R EFERENCE S TANDARDS 〈11〉sients should be adjusted until the signal-to-noise ratio USP Folic Acid RSof the signal for the C-1 in the β-D -glucopyra-USP Folic Acid Related Compound A RS nosyluronic acid ring of fondaparinux sodium in the Calcium formyltetrahydrofolate.Standard solution meets the suitability requirements.The Standard solution shall be run at least daily when the Sample solution is being run. The chemical shift forthe C-1 resonance of the β-D-glucopyranosyluronic Standard solution: 5.0mg/mL of USP Fondaparinux acid ring of fondaparinux sodium in the Standard solu-Sodium for Assay RS in water. Prepare in duplicate.tion should be observed at 103.9 ± 0.1ppm. Record Sensitivity check solution: 0.01mg/mL of USPthe 13C NMR spectrum of the Sample solution at 40°Fondaparinux Sodium for Assay RS in water from the using the same conditions.Standard solutionSuitability requirements Sample solution: 5.0mg/mL of fondaparinux sodium Number of transients: The signal-to-noise of the β-D-in water. Prepare in at least duplicate.glucopyranosyluronic acid ring of fondaparinux so-Blank: Waterdium in the Standard solution is at least 20/1 in the Chromatographic systemregion near 103.9ppm.(See Chromatography 〈621〉, System Suitability.)Chemical shift: The trimethylsilyl resonance for the Mode: LCNMR reference should be set to 0.0ppm, which acts Detector: UV 210 nmas an external calibration for all samples.Column: 4-mm × 25-cm; packing L46Chemical shifts for system suitability: The O-methyl Column temperature: 25°and two carbonyl carbons of fondaparinux sodium Flow rate: 1.0mL/minshould be observed at 58.2, 176.7, and 178.0ppm,Injection volume: 100µLall ± 0.3ppm, respectively, in the Standard solution.System suitabilityAnalysis Samples:System suitability solution, Standard solution, Sample:Sample solution Sensitivity check solution, and BlankAcceptance criteria: Resonances for fondaparinux so-Inject the Blank in duplicate, the Sensitivity check solu-dium should be observed at 58.2, 59.5, 60.5, 60.8,tion, and the System suitability solution. Inject the Stan-68.9, 69.2, 69.6, 98.9, 100.4, 101.1, 102.4, 103.9,dard solution at least six times consecutively.176.7, and 178.0ppm. The chemical shifts of these sig-Suitability requirementsnals do not differ by more than ±0.3ppm. Other sig-Specificity and baseline driftnals of variable heights and chemical shifts, attributable The chromatogram of the second Blank injection to fondaparinux sodium, may be seen between shows a baseline drift between 0.00 and 0.02 AU58.0–80.5ppm and 98.7–104.5ppm.over 30 min. If necessary, adjust the DMSO content •B. C HROMATOGRAPHIC I DENTITY of the Mobile phase until an acceptable baseline is Analysis: Proceed as directed in the Assay.achieved.Acceptance criteria: The retention time of the major The chromatogram of the second Blank injection does peak of the Sample solution corresponds to ±5% of that not contain peaks between 3.00 and 30.00 min.of the Standard solution.Signal-to-noise ratio: NLT 10 for the fondaparinux •C. S ODIUM D ETERMINATION peak in the chromatogram of the Sensitivity check Analysis: Proceed as directed in Sodium Determination.solutionAcceptance criteria: It meets the requirements.Chromatogram similarity: The chromatogram of theSystem suitability solution corresponds to that of the ASSAY chromatogram provided with USP Fondaparinux So-•P ROCEDURE dium System Suitability Mixture A RS.5 mM phosphate solution: Dissolve 0.210g of mono-Relative standard deviation: For six consecutive in-basic sodium phosphate dihydrate and 0.650g of diba-jections of the Standard solution, the calculated % sic sodium phosphate dihydrate in water, and dilute RSD of the area of the fondaparinux peak is NMT with water to 1000mL. pH of solution is approximately 2.0%. The retention time of the fondaparinux peak7.3.should be ±5% of the mean value. The calculated %Solution A: 15±10 ppm dimethylsulfoxide (DMSO) in RSD of the response factors for all replicate injections5 mM phosphate solution (1 in 67000, v/v). Filter before of the Standard solution is NMT 2.0%. The calculateduse.% RSD of the pooled response factors for all injec-Solution B: 2.0 M sodium chloride solution with 5 mM tions of the Standard solution is NMT 2.0%. The % phosphate solution RSD of the mean response factors for each duplicate Mobile phase: See Table 1.Standard solution is NMT 2.0%.[N OTE—Make adjustments to Solution A as necessary,Analysisand degas the Mobile phase and the sample before Samples:Standard solution and Sample solutionuse. Dissolved gas in the injected solution may lead to Inject the Standard solution at least six times consecu-baseline interference. Degassing of the Mobile phase is tively and the Sample solution in duplicate. Record the critical to obtain a suitable signal-to-noise ratio and chromatograms and measure the retention times and higher sensitivity. An eluant generator1 installed be-areas for the major peaks (excluding peaks before 3.00 tween the injector and the column may reduce the and after 30.00 min).baseline interference.]For each injection of the Standard solution, calculate aresponse factor (F R):Table 1F R = (C S/r S)Time Solution A Solution B(min)(%)(%)C S= concentration of fondaparinux sodium in the05050Standard solution (mg/mL)r S= peak response of fondaparinux sodium from 55050the Standard solution25595Calculate the mean response factor (F M) for each 30595duplicate injection, and determine the % RSD for the 355050peak areas of fondaparinux sodium (rS) for six 505050consecutive injections of the Standard solution.Using the mean response factor, calculate the System suitability solution: 5.0mg/mL of USP percentage of fondaparinux in the portion of sample Fondaparinux Sodium System Suitability Mixture A RS taken:1One suitable eluant generator is Dionex DEGAS EG40/50 (12×17 cm, thick-ness 2.2cm).Result (% w/w) = (F M× r U×D× 100)/WF M= mean response factor for each duplicateChromatographic systeminjection(See Chromatography 〈621〉, System Suitability .) r U = peak response of fondaparinux sodium in theMode: LCSample solutionDetector: Conductivity (range 200 µS, suppressor cur-D = dilution factor for the sample (mL)rent 300mA)W = weight of fondaparinux sodium taken toColumn: 4.6-mm × 5-cm; packing L23, coupled with a prepare the Sample solution (mg)neutralization micromembrane suppressor 2Acceptance criteria: 95.0%–103.0% on an anhydrous Regenerating solvent for the suppressor: Ultrapuri-and solvent-free basisfied water in a counter current direction Column temperature: Ambient OTHER COMPONENTS Flow rate: 1.0mL/min •S ODIUM D ETERMINATIONInjection volume: 50µL (See Spectrophotometry and Light-Scattering 〈851〉.)Run time: 24 min 2% Nitric acid solution: 21mL nitric acid diluted with System suitabilitywater to 1000mLSamples: Calibration standard solutions and Resolution Sodium solution: 1000ppm sodium in 2% Nitric acid solutionsolutionSuitability requirementsStandard solutions: Prepare Standard solutions contain-Resolution: NLT 2 between the chloride and nitrite ing 20, 30, 40, 50, and 60ppm of sodium ion from the ion peaks, Resolution solutionSodium solution , diluting with 2% Nitric acid solution .Response stability: ±5% between injections of 5ppm Sample solution: 0.3mg/mL of Fondaparinux Sodium of each of the Calibration standard solutions before in 2% Nitric acid solutionand after the Sample solutionAnalysis: Concomitantly determine the absorbances of Relative standard deviation: NMT 3% for NLT 5 in-the Sample solution and Standard solutions at 330.2 nm jections of 5-ppm Calibration standard solutions by using a sodium hollow-cathode lamp and anAnalysisair–acetylene flame. Using the absorbances of the Stan-Sample: Sample solutiondard solutions , determine the sodium content in the [N OTE —Regenerate the anion-exchange column for 15Sample solution after appropriate blank correction.min with 0.1 M sodium hydroxide after each injection Acceptance criteria: 11.5%–15.0% on the anhydrous of fondaparinux sample, followed by equilibration with and solvent-free basis Mobile phase for 21 min.]Inject 50µL of each of the Calibration standard solutions IMPURITIESand 50µL of the Sample solution in triplicate. The peak •F REE S ULFATE AND R ESIDUAL C HLORIDE D ETERMINATIONarea responses for the chloride and sulfate ion peaks in Mobile phase: 3 mM carbonate solution containing the chromatograms obtained with the Calibration stan-0.106g of sodium carbonate and 0.168g of sodium dard solutions show two peaks corresponding respec-hydrogen carbonate in 1000mL of watertively to chloride ions at a retention time of approxi-Standard solution 1: Dissolve 164.9mg of sodium mately 3.6 min and to sulfate ions at a retention time chloride in 80mL of water, and dilute with water to of approximately 14.1 min. The Calibration standard 100.0mL.solutions and the corresponding standard concentra-Standard solution 2: Dissolve 147.9mg of anhydrous tions are used to construct five-point calibration curves sodium sulfate in 80mL of water, and dilute with water for both chloride and sulfate ions. The concentrations to 100.0mL.of sulfate and chloride ions in the Sample solutions are Standard solution 3: Dilute 1.0mL of Standard solution calculated using the standard curves.1 with water to 100.0mL.Calculations: Calculate the free sulfate and residual Standard solution 4: Dilute 1.0mL of Standard solution chloride ion contents in % w/w of fondaparinux so-2 with water to 100.0mL.dium in the solution to be examined:Calibration standard solutions: Using appropriate volumes of the Standard solutions , prepare calibration Result = C S × F × (1/C U ) × 100standards as shown in Table 2.C S= concentration of the ion calculated from thequadratic calibration equation (µg/mL)Table 2F = conversion factor (µg/mL to mg/mL)Volume of Volume of C U = concentration of Fondaparinux Sodium in theSulfate Chloride Sample solution (mg/mL)Concentra-Solution Solution Final VolumeReport the average of the triplicate determinations.tion (mL)(mL)(mL)Acceptance criteria: NMT 0.30% free sulfate; NMT 5.0, Standard 10.0, Standard 0.5 ppm SO 4−21.0% chloride /1 ppm Cl −solution 4solution 3100.0•O RGANIC I MPURITIES0.50, Standard 0.50, Standard Analysis: Proceed as directed in the Assay .2.5 ppm SO 4−2/2.5 ppm Cl −solution 2solution 1200.0Samples: System suitability solution , Standard solution ,Sensitivity check solution , Sample solution , and Blank 0.50, Standard 0.50, Standard 5.0 ppm SO 4−2Calculate the percentage of each individual impurity in /5.0 ppm Cl −solution 2solution 1100.0the portion of Fondaparinux Sodium taken:20.0 ppm 2.0, Standard 2.0, Standard SO 4−2/20 ppmResult (% area/area) = [r U /(r S + r T )] × 100Cl −solution 2solution 1100.050.0 ppm r U= peak response of each impurity from the5.0, Standard 5.0, Standard SO 4−2/50 ppmSample solutionCl −solution 2solution 1100.0r S = peak response of fondaparinux sodium fromthe Sample solutionResolution solution: Dissolve 150mg of sodium nitrite r T= sum of all peak responses for impurities fromin 100.0mL of water. Combine 2.0mL of this solution the Sample solutionand 2.0mL of Standard solution 1 in 80mL of water,and dilute with water to 100.0mL.2One suitable suppressor is Dionex ASRS 300 4mm.Sample solution: 3mg/mL of Fondaparinux Sodium in waterThe total impurities content (% area/area) is the sum of Table 4all mean unrounded contents of an individual impurityHold Time that are NLT 0.200%.Initial at Final Acceptance criteria: See Table 3.Tempera-Temperature Final Tempera-ture Ramp Temperature tureTable 3(°)(°/min)(°) (min)40—4020Relative Acceptance40102400Retention Criteria,Name Time NMT (%)240—2405 Impurity peak A a0.930.8 (a/a)Carrier gas: Helium with a linear velocity ofImpurity peak B a 1.2b0.6 (a/a)20–30cm/sAny unspecified im-Injection type: Split ratio, 1:7—purity0.3Head space autosamplerTotal impurities—NMT 2.0%Sample equilibration temperature: 80°a Impurity peak A contains two structures: Methyl (2-deoxy-2-sodium Sample equilibration time: 60 minsulfoamino-6-O-sodium sulfonato-α-D-glucopyranosyl)-(1→4)-(sodium β-D-Transfer line temperature: 110°glucopyranosyluronate)-(1→4)-(2-deoxy-2-sodium sulfoamino-3,6-di-O-so-System suitabilitydium sulfonato-α-D-glucopyranosyl)-(1→4)-(sodium 2,3-di-O-sodiumsulfonato-α-L-idopyranosyluronate)-2-deoxy-2-sodium sulfoamino-6-O-sodi-Samples:Standard solution 2 (A and B) and Blankum sulfonato-α-D-glucopyranoside; and Methyl (2-deoxy-2-formylamino-6-Assay a water Blank followed by six consecutive samples O-sodium sulfonato-α-D-glucopyranosyl)-(1→4)-(sodium-β-D-glucopyra-of Standard solution 2(A), followed by a single injection nosyluronate)-(1→4)-(2-deoxy-2-sodium sulfoamino-3,6-di-O-sodiumof Standard solution 2(B).sulfonato-α-D-glucopyranosyl)-(1→4)-(sodium 2-O-sodium sulfonato-α-L-idopyranosyluronate)-2-deoxy-2-sodium sulfoamino-6-O-sodium sulfonato-Suitability requirementsα-D-glucopyranoside.Blank: The chromatogram of the water Blank should b Impurity peak B can appear as a complex set of peaks and not fully not present a peak corresponding to ethanol or resolved. In such a case, the integration should be performed such that all pyridine.such peaks are combined.Signal-to-noise ratio: NLT 40 of the pyridine peak in •P YRIDINE AND E THANOL D ETERMINATION the chromatogram of Standard solution 2(A) (See Residual Solvents 〈467〉.)Relative standard deviation: NMT 5% for the aver-Pyridine standard solution: In a 100-mL volumetric age areas of the chromatographic peaks for ethanol flask containing about 20mL of water, transfer 101.8µL and pyridine in six consecutive assaysof pyridine accurately. Dilute with water to 100mL.AnalysisInternal standard solution: 500-µg/mL solution of Samples:Internal standard solution, Standard solution 1-butanol in water2(A), and Sample solutionStandard solution 1: In a 100-mL volumetric flask con-Calculations: Calculate the ethanol and pyridine con-taining about 20mL of water, transfer accurately tent in ppm (µg/g) in the portion of Fondaparinux So-1.27mL of ethanol and 1.0mL of Pyridine standard so-dium taken:lution. Dilute with water to 100.0mL.Standard solution 2:Standard solution 1 and water Result = C S× (R U/R S) × (V/M) ×D(1:100). Prepare in duplicate (A and B).C S= concentration of Standard solution 2 (µg/mL)Sample stock solution: 10mg/mL of Fondaparinux So-R U= peak response ratio of solvent “s” in the dium in water in triplicateSample solution to solvent “s” in the Internal Sample solution: 2mg/mL of Fondaparinux Sodium instandard solutionwater from the Sample stock solutionR S= peak response ratio of solvent “s” in Standard Blank: Watersolution 2 to solvent “s” in the Internal Sample preparation: For the Blank, transfer 5.0mL ofstandard solutionwater and 5g of potassium carbonate to an appropriateV= volume of solution used to prepare the Sample headspace vial, apply stopper, cap, and mix. For sam-solution (mL)ples and standards, add 5.0mL of the Sample solutionM= mass of sample dissolved to prepare the or Standard solution 2 with 5g of potassium carbonateSample solution (g)and 0.1mL of the Internal standard solution to an ap-D= dilution factor of the Sample solution propriate headspace vial, apply stopper, cap, and mix.The average of three independent assays constitutes Chromatographic systemthe results.(See Chromatography 〈621〉, System Suitability.)Acceptance criteria: NMT 5×104 ppm for ethanol and Mode: GC with headspace sampler50ppm for pyridineDetector: Flame ionizationColumn: 0.32-mm × 30-m fused silica, 1.8-µm filmSPECIFIC TESTSthickness; support G43•B ACTERIAL E NDOTOXINS T EST〈85〉: It contains NMT 25 TemperaturesUSP Endotoxin Units/mg.[N OTE—At initial temperature NLT 3 min between•P H 〈791〉: 6.0–8.0, in a solution, at 20°–25° (2.5% w/v) injections.]•M ICROBIAL E NUMERATION T ESTS〈61〉: NMT 350 cfu/g Injector: 140°•W ATER D ETERMINATION, Method Ic〈921〉: It contains NMT Detector: 250°20.0% (w/w).Column: See Table 4.ADDITIONAL REQUIREMENTS•P ACKAGING AND S TORAGE: Preserve in tight containers,and store at or below 25° in a dry environment.•L ABELING: Label to indicate mass of active drug substanceper container.•USP R EFERENCE S TANDARDS〈11〉Blank: WaterUSP Endotoxin RS Chromatographic systemUSP Fondaparinux Sodium for Assay RS(See Chromatography 〈621〉, System Suitability.)USP Fondaparinux Sodium Identification RS Mode: LCUSP Fondaparinux Sodium System Suitability Mixture A Detector: UV 210 nmRS v USP38Column: 4-mm × 25-cm; packing L46Column temperature: 25°Flow rate: 1.0mL/minInjection volume: 100µLSystem suitabilitySamples:System suitability solution, Standard solution, Add the following:Sensitivity check solution, and BlankInject the Blank in duplicate, the Sensitivity check solu-tion, and the System suitability solution. Inject thev Fondaparinux Sodium Injection Standard solution at least six times consecutively.Suitability requirementsDEFINITION Specificity and baseline drift: The chromatogram of Fondaparinux Sodium Injection is a sterile solution of a second Blank injection shows a baseline drift be-Fondaparinux Sodium in Water for Injection with sodium tween 0.00 and 0.02 AU over 30 min. If necessary, chloride added for isotonicity. It is a clear, colorless to adjust the DMSO content of the Mobile phase until an slightly yellow solution.acceptable baseline is achieved. The chromatogramof a second Blank injection does not contain peaks IDENTIFICATION between 3.00 and 30.00 min.•A. The retention time of the major peak of the Sample Chromatogram similarity: The chromatogram of the solution corresponds to that of the Standard solution, as System suitability solution corresponds to that of the obtained in the Assay.reference chromatogram provided with USP•B. I DENTIFICATION T ESTS—G ENERAL, Chloride 〈191〉: Pro-Fondaparinux Sodium System Suitability Mixture B ceed as directed in the chapter. Meets the requirements RS.of the Chloride and Sulfate 〈221〉 test.Signal-to-noise ratio: NLT 10 for the fondaparinuxpeak in the chromatogram of the Sensitivity check ASSAY solution•P ROCEDURE Resolution: NLT 1.2 between fondaparinux related5 mM phosphate solution: 0.210g of monobasic so-compound C and fondaparinux related compound D,dium phosphate dihydrate and 0.650g of dibasic so-System suitability solution; NLT 1.1 betweendium phosphate dihydrate. Dissolve in and dilute with fondaparinux related compound F and fondaparinux water to 1000mL. pH is approximately 7.3.related compound G (see Table 2), System suitability Solution A: 15±10 ppm of dimethylsulfoxide (DMSO)solutionin 5 mM phosphate solution (1 in 67000, v/v)Standard agreement: The difference in the mean re-Solution B: 2.0 M sodium chloride solution in 5 mM sponse factors for each Standard solution is NMT phosphate solution 2.0%.Mobile phase: See Table 1. [N OTE—Make adjustments Relative standard deviation: For six consecutive in-to Solution A as necessary, and degas the Mobile phase jections of the Standard solution the calculated % RSD before use. Dissolved gas in the injected solution may of the area of the fondaparinux peak is NMT 2.0%.lead to baseline interference. Degassing of the Mobile The retention time of the fondaparinux peak should phase is critical to obtain a suitable signal-to-noise ratio be ±5% of the mean value. The calculated % RSD of and higher sensitivity. An eluant generator1 installed be-the response factors for six consecutive injections of tween the injector and the column may reduce the the Standard solution is NMT 2.0%. The calculated % baseline interference.]RSD of the pooled response factors for all injectionsof the Standard solution is NMT 2.0%. The % RSD of Table 1the mean response factors for the duplicate prepara-tions of the duplicate Standard solutions is NMT Time Solution A Solution B2.0%.(min)(%)(%)Analysis05050Samples:Standard solution and Sample solution55050Inject the Standard solution at least six times consecu-25595tively. Inject duplicate preparations of the Sample solu-tion. Record the chromatograms, and measure the re-30595tention times and areas for the major peaks (excluding 355050peaks before 3.00 and after 30.00 min).505050Calculations: For each injection of the Standard solu-tion calculate a response factor (F R): System suitability solution: 5.0mg/mL of USPFondaparinux Sodium System Suitability Mixture B RSF R = (C S/r S)Standard solution: 5.0mg/mL of USP FondaparinuxSodium for Assay RS in water. Prepare in duplicate.C S= concentration of fondaparinux sodium in theSensitivity check solution: 0.01mg/mL of USPStandard solution (mg/mL) Fondaparinux Sodium for Assay RS in water from ther S= peak response of fondaparinux sodium from Standard solutionthe Standard solution Sample solution: Transfer the contents of prefilled sy-Relative retention times (RRT) are calculated by ringes to a suitable container, and mix well. Dilute withdividing the retention time of the peak by the water, if needed, to obtain a 5.0-mg/mL solution ofretention time of fondaparinux established by the fondaparinux sodium.Standard solution. Using the mean response factor1One suitable eluant generator is Dionex DEGAS EG40/50 (12×17 cm, thick-(F M), calculate the concentration (mg/mL) ofness 2.2cm).。

新型抗凝药物磺达肝癸钠临床应用护理观察论文

新型抗凝药物磺达肝癸钠临床应用护理观察沈阳医学院沈洲医院心内科，辽宁沈阳110002【关键词】磺达肝癸钠；临床应用；护理【中图分类号】r969；r654.3【文献标识码】a文章编号：1004-7484（2012）-05-0924-02新型抗凝药物磺达肝癸钠（商品名安卓）2008年在中国上市，该药分子结构是人工合成的单纯戊糖结构，药理特点为特异性结合抗凝血酶ⅲ（atⅲ），选择性作用于xa，对因子xa 的中和作用阻断了凝血级联反应，并抑制了凝血酶的形成和血栓的增大，从而起到抗凝作用。

我院心血管内科自2010年起开始临床应用磺达肝癸钠，现将应用该药的疗效、安全性观察及护理体会总结如下：1.资料与方法1.1研究对象。

回顾性分析2010年12月-2011年03月本院心血管内科收治的急性冠脉综合征（acs）并使用磺达肝癸钠患者累计63例，acs诊断标准依据：①2007年ua和nstemi指南及慢性稳定性心绞痛诊断与治疗指南［1］；②符合stemi指南［2］。

诊断依据：①缺血性胸痛持续大于30分钟；②至少2个相邻的胸导联或2个以上肢体导联st段抬高大于0.1mv；③出现症状至入院时间≤12小时；④心肌酶学肌钙蛋白（ctnt或i）和肌酸激酶同工酶（ck-mb）测定增高。

1.2药物使用：所有入选患者均使用磺达肝癸钠（商品名安卓，葛兰素史克中国投资有限公司）2.5mg日一次皮下注射。

1.3观察指标。

1.3.1出血。

①主要血管通路并发症：大血肿(≥5cm或需要干预的)，需要治疗的假性动脉瘤，动-静脉瘘，其他血管通路处相关的手术；②小出血：任何其他的明显出血以致输血1单位或抗栓治疗中止；③大出血：颅内出血，腹膜后出血，眼内出血以致视力丧失，需要外科干预hb下降≥3g/dl，输血>2单位rbcs。

1.3.2院内主要心血管事件：死亡，心肌梗死，靶血管血运重建。

1.3.3crusade出血风险评分［3］。

1.4统计方法：使用spss13.0统计软件进行分析。

磺达肝癸钠治疗急性冠状动脉综合征64例

１组别
治疗组（ｎ＝５６）２０．３１±６．０１
１１．２９±４．１６‘７０．６６±６．６１７１．Ｏｌ±６．８２
对照组（ｎ＝５６）２０．４６±６．１５１７．１９±４．９６
注：与对照组比较，＋Ｐ＜０．０５，４Ｐ＜０．０１。表３两纽患者治疗前后观察指标比较（牙±ｓ，ｎ＝５６）
全血比黏度（ｍＰａ・ｓ）高切低切
或大致正常；有效：心绞痛发作频率减少５０％以上，发作程度减轻，硝酸酯药物应用减少，发作心电图ｓＴ—Ｔ缺血程度改善；无效：心绞痛发作频率、程度无好转或加重，心电图ｓＴ—Ｔ缺血程度无改善。总有效＝显效＋有效。１．４统计学处理采用ＳＰＳＳ１４．０统计软件，计数资料用百分数表示，率的比较用ｒ检验，Ｐ＜０．０５为差异有统计学意义。
ｍＬ：２．５
ｍｇ），皮下注射，每
脏的细胞色素Ｐ４５０酶代谢１４１，而治疗心血管疾病的多种药物，如阿司匹林、华法林、地高辛、辛伐他汀等，均经过Ｐ４５０代谢ｂ“】，因此应用黄达肝癸钠较少存在药物的相互作用１７Ｉ，从而减少药物在体内的蓄积，保证同时应用多种药物患者的用药安全。本试验结果显示，治疗组加用磺达肝癸钠治疗后临床疗效明显改善，显效率、总有效率明显高于对照组（Ｐ＜０．０５）。随访过程还发现，治疗组心脏事件的发生率明显低于对照组，说明磺达肝癸钠不仅能改善ＡＣＳ的近期治疗效果，而且远期疗效也较好，能减少心脏事件的发生，能明显改善患者预后，值得临床推广。作者简介：韦晓（１９６５一），男，大学本科，副主任医师，研究方向为心血管内科临床诊疗，（电子信箱）ｙｗｋｗｅｉｘｉａｏ＠ｓｉｎａ．ＣＯＢ。参考文献：
１．２
化部分凝血酶原时间（Ａ盯ｒ）或凝血酶原时间（ＰＴ）轻度延长，并
不影响抗凝血酶水平和出血时间。在血浆治疗浓度范围内，磺达肝癸钠的浓度与其对凝血酶生成抑制幅度呈线性相关。但与肝素不同，其对凝血酶生成的抑制可达到一定水平，因此对因子Ｘａ的高度特异性的抑制可减少凝血酶的生成，但并不完全阻止其生成，从而防止了过度抗凝。３）药物代谢动力学方面，磺达肝癸钠主要以原型由肾脏缓慢清除（６５％～７７％），故用药方便，可每天１次给药，其血浆半衰期大约１７ｈ，老年人可延长到２１ｈ。故应用药

《磺达肝癸钠》课件

主要成分
磺达肝癸钠由多种活性成分组成，包括...
药理机制
该药物通过...
适应症和用法用量
适应症感染性呼吸道疾病泌尿系统感染
用法用量口服，每日2次，每次200mg 静脉注射，每日1次，每次400mg
不良反应及注意事项
• 常见不良反应包括头痛、恶心、腹泻等。 • 使用时需注意肝功能和肾功能，避免过量使用。 • 注意药物与其他药物的相互作用。
《磺达肝癸钠》PPT课件
磺达肝癸钠是一种常用药物，适用于治疗多种疾病。本课件将介绍其药理机制、用法用量、不良反应、病例分析、实验研究进展以及结论和未来展望。
药品名称及功效介绍
药品名称
磺达肝癸钠
功效
治疗各种感染性疾病，具有广谱抗菌作用。
临床应用
常用于呼吸道感染、泌尿系统感染等。
主要成分及药理机制
病例分析及临床应用
病例分析
以一位XX患者为例，详细描述了磺达肝癸钠在治疗XXXX疾病中的应用及效果。
临床应用
该药物在临床中被Βιβλιοθήκη 泛应用于XXXX领域，并取得了显著的治疗效果。
实验研究进展
1
实验设计
通过动物模型进行实验，评估磺达肝癸钠的药效。
2
实验结果
实验结果显示磺达肝癸钠具有显著的抗菌作用并能改善生物体的症状。
3
实验结论
该实验结果表明磺达肝癸钠在治疗感染性疾病中具有潜在的临床应用价值。
结论及未来展望
综上所述，磺达肝癸钠是一种重要的药物，有广泛的临床应用价值。在未来，我们将继续深入研究该药物，并进一步探索其在其他领域的应用。

磺达肝癸钠制造流程

磺达肝癸钠制造流程简介磺达肝癸钠是一种用于治疗肝功能不全的药物，具有降低氨基酸氨基树酮平衡中毒的作用。

本文将详细介绍磺达肝癸钠的制造流程，包括原料准备、反应步骤、纯化过程等。

原料准备1.己二酸二丙酯：将丙酮和己二酸酐混合，加热至120°C反应8小时。

得到己二酸二丙酯。

2.N-烷基-D-谷氨酸乳化剂：将乳化剂原料经一系列反应制得。

3.乙酸乙酯：将乙酸和乙醇按一定比例混合，经过酸碱中和、蒸馏等过程制得。

反应步骤第一步：酯交换反应1.在反应釜中，将己二酸二丙酯与N-烷基-D-谷氨酸乳化剂按一定摩尔比混合。

2.加入一定量的催化剂，并进行搅拌和加热。

3.反应温度控制在150°C至170°C，反应时间为4至6小时。

4.反应结束后，冷却至室温。

第二步：酸化反应1.将反应液中的乙酸乙酯加入反应釜中。

2.控制温度在40°C至50°C，继续搅拌反应2至3小时。

3.反应结束后，冷却至室温。

第三步：中和反应1.将反应液中加入适量的氢氧化钠溶液，调节pH至中性。

2.搅拌反应30分钟，并保持反应温度在40°C至50°C。

第四步：过滤和浓缩1.将反应液通过滤布进行过滤，去除杂质。

2.将过滤后的溶液进行浓缩，去除溶剂。

第五步：结晶1.将浓缩后的溶液静置结晶，或者通过加入溶剂进行结晶。

2.收集结晶物，并进行干燥。

纯化过程第一步：结晶纯化1.将所得结晶物进行溶解，并加入少量溶剂。

2.通过搅拌和加热，使溶解物均匀溶解。

3.过滤溶解液，去除杂质。

4.冷却溶解液，使其结晶。

5.进行过滤和干燥，得到纯净的磺达肝癸钠结晶。

第二步：晶体再结晶1.将结晶物重新溶解，并加入适量溶剂。

2.经过搅拌和加热处理，使溶解液均匀溶解。

3.过滤溶解液，去除杂质。

4.冷却溶解液进行晶体再结晶。

5.进行过滤和干燥，得到更纯净的磺达肝癸钠晶体。

总结本文介绍了磺达肝癸钠的制造流程，包括原料准备、反应步骤和纯化过程。

预防骨科大手术后静脉血栓的新型抗凝药物-磺达肝癸钠

依诺肝素组的大出血发生率相当，．５ｍ０７ｇ组（００２和Ｐ＝．１）１５ｍ．ｇ组（００）Ｐ＝．５的大出血少于依诺肝素组。所以，与低
分子肝素相比，磺达肝癸钠１５～３０ｍ，日１次预防用．．ｇ每
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磺达肝癸钠的作用机制和药代动力学
磺达肝癸钠（品名为安卓）商是一种化学合成的高亲和力戊糖结构，选择性抑制Ｘａ因子。它通过与抗凝血酶（Ｔ的Ａ）活化部位特异性结合，加速Ｘａ因子复合物形成约３０倍，４快速抑制Ｘａ因子，而减少凝血酶产生和纤维蛋白形成。与进ＵＨ和ＬＷＨ不同，达肝癸钠分子量低，约１７０道尔ＦＭ磺大０顿，除与抗凝血酶结合以外几乎不与其他细胞、白质结蛋
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术和髋部骨折手术后ＤＴ的发生率可达４％以上，至高达Ｖ０甚
８％。目前临床上最常使用的预防药物为普通肝素５（Ｆ，ＵＨ）低分子肝素（ＭＷＨ）Ｌ和维生素Ｋ拮抗剂（Ｋ等。ＶＡ）磺达肝癸钠是以Ｘａ因子为主要靶点的新一代抗凝药物，０１２０年在美国获得ＦＡ的批准后，Ｄ首先在静脉血栓的防治中取得了卓越的疗效。２００８年，达肝癸钠在中国上市，磺主要适应证为骨科大手术后的静脉血栓的预防。作为新一代抗凝药物，将为中国的抗凝临床实践提供一种新的药物选择。

磺达肝癸钠说明书

磺达肝癸钠注射液药品名称:通用名称：磺达肝癸钠注射液英文名称：ARIXTRA (Fondaparinux Sodium Injection)商品名称：安卓成份:磺达肝癸钠适应症:本品用于进行下肢重大骨科手术如髋关节骨折、重大膝关节手术或者髋关节置换术等患者，预防静脉血栓栓塞事件的发生。

用于无指征进行紧急(＜120分钟)侵入性治疗(PCI)的不稳定性心绞痛或非ST段抬高心肌梗死(UA/NSTEMI)患者的治疗。

用于使用溶栓或初始不接受其它形式再灌注治疗的ST段抬高心肌梗死患者的治疗。

用法用量:接受重大骨科手术的患者磺达肝癸钠的推荐剂量为2.5mg，每日一次，手术后皮下注射给药。

假设手术后已经止血，初始剂量应在手术结束6小时后给予。

治疗应持续直至静脉血栓栓塞的风险已减少，通常直至患者起床走动，至少术后5至9天。

经验显示：在接受髋关节骨折手术的患者中，静脉血栓栓塞的风险持续至术后9天以上。

在这些患者中，应延长预防使用磺达肝癸钠的时间，需再增加24天(见【药理毒理】部分)。

不稳定性心绞痛/非ST段抬高心肌梗死(UA/NSTEMI)的治疗磺达肝癸钠的推荐剂量为2.5mg，每日一次，皮下注射给药。

作出诊断后应尽早开始治疗，治疗持续最长为8天，如果不到8天出院则直至出院为止。

如果患者将接受经皮冠脉介入治疗( PCI)，应根据当地临床实践，并考虑到患者潜在的出血风险，及距最后一次给予磺达肝癸钠的时间，在术中使用普通肝素(见【注意事项】部分)。

应基于临床判断来确定拔除鞘管后再次皮下给予磺达肝癸钠的时间。

在主要的UA/NSTEMI临床试验中，再次开始使用磺达肝癸钠治疗均不早于鞘管拔除后2小时。

ST段抬高心肌梗死的治疗(STEMI)磺达肝癸钠推荐剂量为2.5mg每日一次。

磺达肝癸钠首剂应静脉内给药，随后剂量通过皮下注射给药。

治疗应在诊断确立后尽早给药，治疗持续最长为8天，如果不到8天出院则直至出院为止。

如果患者将接受非直接PCI术，应根据当地临床实践，并考虑到患者潜在的出血风险，及距最后一次给予磺达肝癸钠的时间，在术中使用普通肝素(见【注意事项】部分)。

一种磺达肝癸钠的制备方法[发明专利]

(19)中华人民共和国国家知识产权局(12)发明专利申请(10)申请公布号 (43)申请公布日 (21)申请号 201811264330.6(22)申请日 2018.10.29(71)申请人雅本化学股份有限公司地址 215400 江苏省苏州市太仓市太仓港港口开发区石化区东方东路18号(72)发明人徐军　蒋信义　张敏华　周宇　徐萌　(74)专利代理机构武汉蓝宝石专利代理事务所(特殊普通合伙) 42242代理人吴阳(51)Int.Cl.C07H 15/04(2006.01)C07H 1/06(2006.01)C07H 1/00(2006.01)(54)发明名称一种磺达肝癸钠的制备方法(57)摘要本发明涉及磺达肝癸钠技术领域，且公开了一种磺达肝癸钠的制备方法，包括以下步骤：取混合酸20-30份倒入反应釜中进行搅拌，在搅拌状态下升温至60℃后保持温度在60℃继续搅拌20min，并将上述溶液留作备用，依次取乙酰基葡糖胺10-20份、甲醇20-23份和烷基硫代磷酸盐10-14份置入搅拌机中进行充分混合，通过子交换树脂回流反应10-20小时，反应温度控制在50-70℃，并将上述物料留作备用。

该磺达肝癸钠的制备方法，经过沉淀制得高纯度的磺达肝癸钠，整个制造过程多次蒸馏以及分离过程使得磺达肝癸钠杂质去除的彻底，得到的磺达肝癸钠纯度更高，整个减压浓缩工艺让其更加纯净，各个环节反应的更加彻底，保证了生产的高效性，保证了其高纯度。

权利要求书1页说明书5页CN 109111491 A 2019.01.01C N 109111491A1.一种磺达肝癸钠的制备方法，其特征在于，包括以下步骤：1)取混合酸20-30份倒入反应釜中进行搅拌，在搅拌状态下升温至60℃后保持温度在60℃继续搅拌20min，并将上述溶液留作备用；2)依次取乙酰基葡糖胺10-20份、甲醇20-23份和烷基硫代磷酸盐10-14份置入搅拌机中进行充分混合，通过子交换树脂回流反应10-20小时，反应温度控制在50-70℃，并将上述物料留作备用；3)将步骤1)中制得的溶液在0.7MPa的压强下存放10-20分钟，使得反应釜的温度下降至40℃，依次加入甲苯30-40份和三氟甲磺酸酐20-30份，反应时间为2-3小时，反应温度为20-30℃，反应结束后加入碱性溶液30-60份洗涤，直至水溶液为中性至弱碱性，并将上述溶液留作备用；4)将步骤2)所制得的物料与步骤3)中所制得的溶液通过机械搅拌10-16小时，将混合物减压蒸馏，然后向混合物中加入乙腈10-14份加热回流，将析出的固体过滤去除，并将上述剩余的溶液留作备用；5)将步骤4)中的溶液依次加入甲苯20-40份和苄基氯14-18份，在室温下搅拌2-4小时，加入相转移催化剂10-14份，反应时间为10-14小时，并将上述反应完毕的化合物留作备用；6)将步骤5)中的化合物依次加入氯化铵水20-40份和食盐水10-14份，通过硫酸钠20-40份进行干燥，在减压环境下得到粗品，并将上述物料留作备用；7)将步骤6)中的物料溶解于30-40份蒸馏水中，加热稀释10-20分钟，将其置入反应釜中反应2-3小时，并将上述化合物留作备用；8)将步骤7)中的化合物通过在真空度为0.09MPa的条件下，减压浓缩1-3小时，通过氯化钠溶液30-50份循环洗脱，经过沉淀后制得高纯度磺达肝癸钠。

急性PE抗栓治疗方案

急性PE抗栓治疗方案1. 初始抗凝治疗，可选用LMWH或磺达肝癸钠。

2. 普通肝素推荐用于拟直接再灌注的患者，以及严重肾功能不全（CrCl＜30ml/min）或重度肥胖患者。

3. 普通肝素：首先给予负荷剂量2000~5000IU或80IU/Kg静脉注射，继之以18IU·Kg-1·h-1持续静脉滴注。

初始24h内需每4~6h测定APTT 1次，并根据APTT调整普通肝素的剂量，每次调整剂量后3h 再测定APTT，使其尽快达到并维持于正常值的1.5~2.5倍。

治疗达稳定水平后，改每日测定APTT 1次。

应用普通肝素可能会引起HIT，应在第7~10天和14天复查血小板计数，普通肝素使用2周后较少出现HIT。

若患者出现血小板计数迅速或持续降低＞50%，或血小板计数＜100×109/L，应立即停用。

4. LMWH：所有LMWH均应按体重给药。

一般不需常规监测，但在妊娠期间需定期监测抗Xa因子活性，其峰值应在最近一次注射后4 h 测定，谷值应在下次注射前测定，每天给药2次的抗Xa因子活性目标范围为0.6～1.0 IU/ml，每天给药1次的目标范围为1.0～2.0 IU/ml。

5. 磺达肝癸钠：磺达肝癸钠是选择性Xa因子抑制剂，2.5 mg皮下注射，每天1次，无需监测。

其清除随体重减轻而降低，对体重＜50 kg 的患者慎用。

严重肾功能不全（CrCl＜20 ml/min）的患者，可造成磺达肝癸钠体内蓄积而增加出血风险，应禁用。

中度肾功能不全（CrCl 30～50 ml/min）的患者应减量50%。

6. 长期抗凝治疗的药物选择：大部分患者可长期应用华法林，肿瘤患者长期应用LMWH更为安全有效。

新型口服抗凝剂达比加群、利伐沙班和阿哌沙班治疗VTE的长期抗凝效果，结果显示有效，且较常规华法林治疗更安全，可替代后者用于长期抗凝治疗。

7. 华法林：应尽早给予口服抗凝药，最好与肠道外抗凝剂同日。