 |
|
Chemists move closer toward developing safer, fully-synthetic form of heparin
August 18, 2008Chemists are reporting a major advance toward developing a safer, fully-synthetic version of heparin, the widely used blood thinner now produced from pig intestines. The U. S. Food and Drug Administration last spring linked contaminated batches of the animal-based product, imported from China, to more than 80 deaths and hundreds of allergic reactions among patients exposed to the drug for kidney dialysis and other conditions.
Described here today at the ACS's 236th National Meeting, the purer, non-animal version could improve the drug's safety and bolster regulatory control of its manufacture, the researchers say. Scientists expect demand for heparin, which prevents blood clots, to increase in the future due to rising rates of diabetes, heart disease, and other health complications linked to sedentary lifestyles. Global heparin sales total about $4 billion annually.
"With the problems associated with contaminated heparin produced from pig tissues in China, a non-animal source of this essential drug is gaining importance," says study co-author Robert J. Linhardt, Ph.D., a chemist with Rensselaer Polytechnic Institute in Troy, New York. "A safer version of the drug could result in less adverse effects and fewer deaths."
Heparin can be given by injection to prevent life-threatening blood clots during heart surgery and kidney dialysis. It also is used to clean intravenous lines used in those procedures. Because heparin is difficult to make in the lab from scratch, the drug's only source has been from pig intestines.
Linhardt points out that processing of pig intestines to extract the raw materials is often done in small, family-run workshops in China, which supplies about 70 percent of the world's heparin. Those mom-and-pop shops often fall outside the normal supervision and regulatory control standard in the pharmaceutical industry. The lack of oversight increases the risks of heparin contamination or adulteration with harmful chemicals, viruses, or other agents, he says.
"If heparin is prepared the right way, it should be consistent and safe, even from an animal source," says Linhardt, who was part of the team that identified the suspected chemical contaminant in the Chinese heparin. The contaminant, called oversulfated chondroitin sulfate, can cause life-threatening allergic reactions. Heparin supplies containing the contaminant have now been recalled.
Researchers have been trying for years to develop heparin production methods that don't require pig intestines. The first so-called total synthesis of heparin, developed in 2003 at the Massachusetts Institute of Technology (MIT), was not practical. It produced only minute batches of heparin - less than 0.000000035 ounces at a time - and could not be scaled up for commercial use, Linhardt says.
Working with Jian Liu, Ph.D., a medicinal chemist with the University of North Carolina-Chapel Hill, and Jonathan Dordick, Ph.D., a Rensselaer chemical engineer, Linhardt's team now has developed an alternative synthesis method that boosts heparin production a million times higher than the MIT technique. The scientists employed a patented biotechnology approach that uses powerful enzymes to string together the individual carbohydrate units that form the pure heparin polymer. "Our biotech version of heparin will be prepared in a controlled environment ensuring that it is pure and free of contaminants," Linhardt says.
So far, only small amounts of the new heparin have been produced in the laboratory using this technique, called "chemoenzymatic synthesis." But Linhardt reports that the new approach can be used to produce the drug on a larger scale suitable for industrial manufacture. Cost, dosing, and administration of the new drug should be the same as conventional, animal-based heparin, he notes.
Linhardt plans to begin testing the synthetic heparin on animals this summer. If these and other tests are successful, the new heparin could reach the consumer market in two to five years, he estimates. The National Institutes of Health provided primary funding for the project.
American Chemical Society
Heparin can be given by injection to prevent life-threatening blood clots during heart surgery and kidney dialysis. It also is used to clean intravenous lines used in those procedures. Because heparin is difficult to make in the lab from scratch, the drug's only source has been from pig intestines.
Linhardt points out that processing of pig intestines to extract the raw materials is often done in small, family-run workshops in China, which supplies about 70 percent of the world's heparin. Those mom-and-pop shops often fall outside the normal supervision and regulatory control standard in the pharmaceutical industry. The lack of oversight increases the risks of heparin contamination or adulteration with harmful chemicals, viruses, or other agents, he says.
"If heparin is prepared the right way, it should be consistent and safe, even from an animal source," says Linhardt, who was part of the team that identified the suspected chemical contaminant in the Chinese heparin. The contaminant, called oversulfated chondroitin sulfate, can cause life-threatening allergic reactions. Heparin supplies containing the contaminant have now been recalled.
Researchers have been trying for years to develop heparin production methods that don't require pig intestines. The first so-called total synthesis of heparin, developed in 2003 at the Massachusetts Institute of Technology (MIT), was not practical. It produced only minute batches of heparin - less than 0.000000035 ounces at a time - and could not be scaled up for commercial use, Linhardt says.
Working with Jian Liu, Ph.D., a medicinal chemist with the University of North Carolina-Chapel Hill, and Jonathan Dordick, Ph.D., a Rensselaer chemical engineer, Linhardt's team now has developed an alternative synthesis method that boosts heparin production a million times higher than the MIT technique. The scientists employed a patented biotechnology approach that uses powerful enzymes to string together the individual carbohydrate units that form the pure heparin polymer. "Our biotech version of heparin will be prepared in a controlled environment ensuring that it is pure and free of contaminants," Linhardt says.
So far, only small amounts of the new heparin have been produced in the laboratory using this technique, called "chemoenzymatic synthesis." But Linhardt reports that the new approach can be used to produce the drug on a larger scale suitable for industrial manufacture. Cost, dosing, and administration of the new drug should be the same as conventional, animal-based heparin, he notes.
Linhardt plans to begin testing the synthetic heparin on animals this summer. If these and other tests are successful, the new heparin could reach the consumer market in two to five years, he estimates. The National Institutes of Health provided primary funding for the project.
American Chemical Society
Heparin Current Events and Heparin News RSSScientists successfully reprogram blood cells
Researchers have transplanted genetically modified hematopoietic stem cells into mice so that their developing red blood cells produce a critical lysosomal enzyme -preventing or reducing organ and central nervous system damage from the often-fatal genetic disorder Hurler's syndrome.
Investigation of contaminated heparin syringes highlights medication safety issues
An outbreak of bloodstream infections appears to have been caused by the contamination of pre-filled heparin and saline syringes made by a single company.
Drug-eluting stents better than bare-metal stents for heart attack patients
Late-breaking data from the landmark HORIZONS-AMI clinical trial, presented at the 21st annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, demonstrated that after two years, in heart attack patients, the use of a drug-eluting stent (paclitaxel) was safer and more effective than a bare-metal stent; and that the administration of the anticoagulant medication bivalirudin enhanced safety and efficacy compared to the use of heparin + GPIIb/IIIa inhibitors.
Otamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes
Data from a phase II trial of an investigational intravenous drug designed to block the formation of blood clots shows potential to reduce the risk of death, a second heart attack, or other coronary complications compared with the current standard of care in patients presenting with acute coronary syndromes (heart attacks or unstable angina).
Patient safety advanced by revised heparin standards
Continuing to help ensure the identity, purity and quality of heparin, the U.S. Pharmacopeial (USP) Convention has revised written and physical standards for the widely used blood thinner.
'Artificial Golgi' may provide new insight into key cell structure
Scientists in New York and North Carolina are reporting assembly of the first functioning prototype of an artificial Golgi organelle.
Research highlights new approaches to prevent blood clots
Blood clotting, or coagulation, is an important process that prevents excessive bleeding when a blood vessel is injured.
Simple new method detects contaminants in life-saving drug
The blood-thinning drug heparin is highly effective when used to prevent and treat blood clots in veins, arteries and lungs, but earlier this year its reputation as a lifesaver was sullied when contaminated heparin products caused serious allergic reactions that led to a large number of deaths.
HORIZONS AMI will help set guidelines for drug and stent therapy
The HORIZONS AMI clinical trial measuring the safety and efficacy of the use of the medication bivalirudin compared to standard drug therapy - heparin and glycoprotein IIb/IIIa inhibitors -- in heart attack patients who receive angioplasty, found that after 1 year, use of bivalirudin resulted in significantly lower rates of all-cause death, death from cardiac causes, and major bleeding.
Safety of antithrombotic treatment in acute coronary syndromes
The management of acute coronary syndromes (with or without ST segment elevation) requires the use of anticoagulants, antiplatelet agents (aspirin, clopidogrel and/or glycoprotein (GP) IIb/IIIa inhibitors), beta-blockers, thrombolytics in some cases, and revascularization / reperfusion.
More Heparin Current Events and Heparin News Articles
 |
Heparin-Induced Thrombocytopenia, Fourth Edition (Fundamental and Clinical Cardiology) by Theodore E. Warkentin (Editor), Andreas Greinacher (Editor) Although first reported in 1973, immune heparin-induced thrombocytopenia (HIT) remains one of the most potentially devastating and frequent adverse drug reactions encountered by physicians. This Fourth Edition reinforces its standing as the leading guide to the accurate diagnosis and management of HIT by identifying key signs and symptoms of this disorder and providing clear intervention strategies, including detailed information on the use of alternative anticoagulants to manage these critical circumstances. Intended for those requiring an expert source of guidance for the quick detection and control of HIT, this reference: contains new chapters on novel pharmacotherapies, recent drug approvals, current dosing guidelines, and... |
 |
Monoject Prefill I.V. Syringes - 12mL Syringe, Filled with 5mL 100U/mL Heparin Flush - 180 Per Case - Model SWD590125 by TYCO/KENDALL Saline and heparin flush syringes.Terminally sterile.Drug stopper quality plunger tip.Color-coded.Low breakforce.Latex and perservative free. |
|
Fisherbrand Micro Blood Collecting Tubes; Heparin; 100/pack by Fisher Scientific Tubes, capillary blood collection; Fisherbrand; Micro blood collecting tubes; caraway; Heparin; Red tip; 100/pack | |
 |
B-d Vacutainer Plus Plastic Plasma Tubes 13 X 100 4.5ml Pst Tube W/ Polymer Gel And Lithium Heparin by Becton-dickinson B-D Vacutainer Plus Plastic Plasma Tubes 13 x 100 4.5mL PST Tube w/ Polymer Gel and Lithium Heparin : BD safety-engineered plastic blood collection tubes provide not only a clinically tested alternative to traditional glass tubes, but also offer you and your staff reduced risk of tube breakage and specimen spillage, thereby reducing risk of exposure to bloodborne pathogens, and are also in compliance with OSHA standards. Sterile. |
|
Heparin and Related Polysaccharides: Structure and Activities (Annals of the New York Academy of Sciences) by Frederick A. Ofosu (Author), Isidore Danishefsky (Author), Jack Hirsh (Editor) | |
 |
60 Minutes - The Wrong Medicine (March 16, 2008) Airdate: 03/16/08 As many as 100,000 people die each year from medical errors, and the newborn twins of actor Dennis Quaid and his wife Kimberly were nearly part of that statistic. When only days old, the babies were accidentally given the wrong dose of the blood thinner Heparin, and they nearly bled to death. Steve Kroft talks with the couple about their ordeal and about the issue of preventable medical mistakes. |
|
Hate Me | |
 |
Site Selection and Injection Techniques (Parenteral Medication Administration) (Volume Four) Also With: Concept Media (Primary Contributor) Discusses common intramuscular injection sites and essential assessment considerations. Concisely describes the techniques for administration of intra-muscular medications with emphasis on the displacement or Z-track method. Subcutaneous site selection is also discussed. Procedures, including specific techniques for insulin and heparin administration, are illustrated in detail. |
|
Hospira Injectables/Multidose Vials - Heparin, 100 units/mL in a 30 mL multidose vial - Qty of 50 by Medline These items will have a delay in shipment due to regulatory issues. | |
 |
Chemistry and Biology of Heparin and Heparan Sulfate by Hari G. Garg (Editor), Robert J. Linhardt (Editor), Charles A. Hales (Editor) The chemistry, biochemistry and pharmacology of heparin and heparan sulfate have been and continue to be a major scientific undertaking - heparin and its derivative remain important drugs in clinical practice. Chemistry and Biology of Heparin and Heparan Sulfate provides readers with an insight into the chemistry, biology and clinical applications of heparin and heparan sulfate and examines their function in various physiological and pathological conditions. Providing a wealth of useful information, no other tome covers the diversity of topics in the field. Students, doctors, chemists, biochemists, and research scientists will find this book an invaluable source for updating their current knowledge of developments in this area. *... |
| © 2009 BrightSurf.com |