Richard T Taylor and Rebecca G Brunner Department of Chemistry and Biochemistry Miami University Oxford OH 45056 USA Heparin Highly charged glycoaminoglycan MW 15000 Binds antithrombin used as anticoagulant ID: 1047134
Download Presentation The PPT/PDF document "Depolymerization of heparin benzyl ester..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
1. Depolymerization of heparin benzyl ester in a flow systemRichard T. Taylor* and Rebecca G. BrunnerDepartment of Chemistry and BiochemistryMiami University, Oxford, OH 45056 USA
2. HeparinHighly charged glycoaminoglycan, MW ~ 15000Binds antithrombin, used as anticoagulantGeneralized structure below:
3. EnoxaparinLow molecular weight heparinFormed by base treatment of heparin benzyl ester Can be delivered subcutaneouslyGeneralized structure below:
4. ObjectiveConvert current batch processed for depolymerization into continuous flowObtain an enoxaparin-like productDevelop conditions informed by current batch methods
5. Protocol Syrris FRX flow system with a 12.05 mL reactor coil (1/16” i.d. tubing) T mixer – combine flowing streams of base and heparin benzyl ester solutionsNeutralize, dilute with methanol, evaporate, dialyze and record HNMR spectrumCompare to enoxaparin USP spectrum
6. Reaction conditions as variedEntryHeparin Ester solutionNaOH solutionFlow ester(mL/min)Flow base(mL/min]T (°C)ReactionTime (min)12g/20mL2g/20mL0.250.257024.122g/20mL2g/20mL0.120.125050.232g/20mL2g/20mL0.120.126550.242g/20mL2g/20mL0.120.127550.252g/20mL2g/20mL0.120.126550.262g/20mL2g/20mL0.240.246525.172g/20mL2g/20mL0.120.145550.282g/20mL2g/20mL0.240.247525.194g/40mL4g/40mL0.240.246525.1104g/40mL4g/40mL0.240.245525.1110.65g/6.5mL0.65g/6.5mL0.480.485512.6121.0g/20mL1.0g/20mL0.240.245525.1131.5g/15mL1.5g/15mL0.480.485512.6
7. Entry 13 – most enoxaparin-like material
8. ConclusionsBase depolymerization of heparin benzyl ester can be converted into a flow processVariation of reaction conditions leads to an enoxaparin-like material in the HNMNR spectrumFurther work to fully convert the purification process into a flow system (desalting, etc.) is needed
9. AcknowledgementSmithfield BioscienceHeparin benzyl esterSupportMiami UniversityProvisional patent on this work has been filed