NoBlood

July 22, 2003

Bloodless coup - chitosan bandage

Written by Cinda Becker

Oregon researchers turn to the sea to develop a revolutionary bandage that stanches heavy bleeding

Story originally published July 14, 2003

An Oregon hospital that was merely trying to give itself an edge in physician recruitment and patient referrals unexpectedly owns a stake in what is arguably the biggest advance in wound dressing since the Civil War.
On the morning of Sept. 11, 2001, Kenton Gregory, director of the Oregon Medical Laser Center, was meeting with military officials at Eglin Air Force Base in Florida. He was showing off the fruit of a $400,000 grant to help solve the battlefield's worst medical treatment problem: how to stop heavy bleeding. His solution was a 4-by-4-inch bandage derived from shrimp shells.

"Then we watched the planes crash into the (World Trade Center) and they said, `We are going to war, and we need to get this through in a year,' " says Gregory, who is an interventional cardiologist and also a chemical engineer.

Eighty percent of the soldiers severely wounded in battle die in the first 10 minutes, mainly from bleeding, a grim statistic that hasn't changed much since the Civil War, Gregory says. Despite amazing advances in medical science, the material to stop bleeding-tourniquets and cotton gauze-hadn't changed until recently.

Scientists everywhere had been working on the problem, but the Army, which had been funding Gregory's unrelated efforts to find a biocompatible material that could be used to make new tissue, told him what it needed more than that was a bandage to stop bleeding. So for two years before that Sept. 11 meeting, Gregory's team at the Oregon Medical Laser Center had been working on the problem. The center is part of the Providence Heart Institute at Providence St. Vincent Medical Center in Portland; Providence St. Vincent is owned by Seattle-based Providence Health System.

Gone fishing

Once they committed to the effort, the Oregon researchers took everything they could find off the shelf and tested it-materials such as various proteins, volcanic dust and collagen, Gregory says. Then a senior chemist from China remembered reading something first reported in the 1950s: that chitosan-derived from chitin, the main ingredient of shrimp shells-attracted red blood cells, causing them to clot. Just applying a shrimp shell to a wound wouldn't work, however. After considerable trial and error, the scientists determined that the shrimp shells have to be boiled in lye and reconstituted into a crystal to make it more positively charged to attract negatively charged cell membranes "like a magnet," Gregory explains.

Though many scientists throughout the world had been working on ways to turn chitosan into a durable bandage, Gregory credits the multidisciplinary approach of his laboratory for the success.

"Here I make everybody work together," he says. Sometimes that has unanticipated results. For example, when a polymer chemist working on the bandage unexpectedly saw blood during one of the early experiments, "I saw his eyebrows go up so far in his forehead I thought they would never come down," Gregory says.

Working for a Catholic-sponsored, not-for-profit hospital, Gregory says he figured he would need some help to meet the military's timeline. He went to the masters of wound care, Johnson & Johnson, and, "They said I was crazy." Then he decided to do it himself, founding a company called HemCon (for hemorrhage control). The Army gave HemCon $700,0000 to produce 5,000 bandages. By June 2002, Gregory had raised about $900,000 for the company, and HemCon was in business. Last October, they broke ground in Portland for a company building and hired a chief executive officer. By November, the Food and Drug Administration had approved HemCon's product for external use only. The first bandages were shipped to the Army and its special forces in March.

Reports from the field

The Army subsequently signed a $2 million contract with HemCon to produce 20,000 dressings. HemCon has vowed to make them affordable and will always sell them to the military for less than $100 each, Gregory says.

As of late June, the company had shipped about 5,000 bandages to the Army, presumably for use in Iraq and Afghanistan-"wherever they think they need it," Gregory says. He says reports are coming in now, and they seem to have worked well for medics. But incredibly the Army has only one confirmed account of its use, says Charles Dasey, public affairs officer for the U.S. Army Medical Research and Materiel Command in Fort Detrick, Md. U.S. Army medics successfully treated an Iraqi prisoner of war who was shot in the foot.

Up until now the developers have been focused on meeting the military's needs, but the bandage promises wide applications for hospitals, especially trauma centers, as well as first responders.

"There's good reason to think this product will become available in civilian medicine," Dasey says.

Gregory notes severe bleeding generates about 70 million emergency room visits nationally each year. The bandage also could have applications in orthopedic surgery, which now typically relies on cotton to passively absorb heavy bleeding, he says.

"Chitosan is a natural glue" and was a substance Stradivarius used to varnish his violins, Gregory says. An added bonus is that it also is a natural antibacterial. Although that's a plus in the ER, that quality also makes it difficult to purify the raw shrimp shells, which tend to bind to bacteria and consequently are often used to treat sewer water, Gregory says.

HemCon has a contract with a shrimp packing plant in Iceland to supply shells. It takes about five days to manufacture each bandage, and with the production expense, including the considerable "frequent flier miles" the shrimp shells tally, the company still is not covering its costs, Gregory says. But Gregory adds that he believes he can make the company profitable in a year after its market expands. HemCon plans to apply to the FDA for additional approval to use the bandage internally to treat severe bleeding and puncture wounds. The company also will try to get it approved for over-the-counter applications.

"It's good for the hospital because the government paid for the research and the hospital will get the royalties. And the real upside is that patient lives will be saved if you can stop the bleeding," Gregory says. "We started out to solve a problem for the soldiers and now when we did that, there's a big civilian need for this."

Gregory says one of the biggest medical companies in the world, which he declined to name, has an unrelated chitosan product and is in discussions with HemCon on an unspecified deal. Gregory says there are plans to take HemCon public, although probably not this year.

Research ROI

The chitosan bandage's fortunes are tied to Providence Health System; Gregory jointly owns the Oregon Medical Laser Center with the Providence Heart Institute. The research center was an added enticement the hospital offered knowing Gregory's interest in research when he was recruited to the heart institute in 1991, says Kristy Wayson, executive director of the Providence Heart Institute. Laser technology reflected his main interest at the time-hence the name-but over the past 13 years, research has evolved related to the interests of all the scientists who work there. The research center now employs 40 people.

"It's difficult to recruit clinically innovative physicians if we can't offer some research components," Wayson says.

The Heart Institute represents Providence St. Vincent's biggest clinical service, with doctors performing 1,500 open-heart surgeries and another 1,500 angioplasties yearly, says John Fletcher, chief administrative officer for the seven Providence hospitals in Oregon. In the most recent numbers available, gross annual revenue at 442-bed Providence St. Vincent was about $875 million. The hospital won't release its annual net income, but Fletcher says it is "a very successful hospital."

The Oregon Medical Laser Center operates on a $4 million annual budget, much of that subcontracted to other organizations. It's a break-even operation with the goal of bringing in enough revenue to offset expenses, Fletcher says. Revenue generally comes in the form of grants and endowments. Soon revenue may start coming from HemCon, although it's too early to make financial projections, he says. The licensing agreement is confidential, but Fletcher says Providence does own a small amount of equity in HemCon.

"Our goal for research is not to generate revenue on investment. It really is to cover our costs and build an endowment for future research," Fletcher says. The hospital's share of any profits from sales of the bandage will be plowed back into the laser center's endowment and ultimately to build on clinical services, he says.

"We're not a university," Fletcher says. "It helps with recruitment and patient referrals, and we are able to introduce new technologies quicker to patients. If we didn't have the research center, then we would just be like any other hospital. We wouldn't be on the cutting edge of the newest technologies."

Competing products

The chitosan bandage has some competition. Z-Medica, a small Newington, Conn., company founded in 2002, supplied its breakthrough QuikClot product to the U.S. ground troops in Afghanistan and Iraq, where it was confirmed to have saved numerous lives, the company says. Launched in May 2002, QuikClot is made of a granulated mineral substance, the exact content of which is proprietary, that is poured directly on a wound to stop high- volume bleeding almost instantaneously. QuikClot went to the Marines and the Navy.

The FDA has cleared QuikClot for general use and also in an over-the-counter consumer version to treat abrasions, cuts and scratches. The consumer version soon will be available in drugstores nationwide, and a veterinary version also is in the works, the company says. One "lifesaving quantity"-3.5 ounces for military use and first responders-retails for a little more than $20, according to Z-Medica.

A consumer version, which would be a fraction of an ounce, should be on the market at the end of the year and retail for about $10 for multiple applications. Besides the military, the company sells to security companies, first responders and other markets through authorized distributors around the world.

Z-Medica and HemCon beat the American Red Cross to the punch. The nation's largest charity has been working on a solution for severe hemorrhaging since World War II, Gregory says. The Army is conducting clinical trials of a wound sealant based on the blood protein fibrin, but the Red Cross can't discuss it because of an agreement with the FDA, says Lesly Hallman, a Red Cross spokeswoman.

War has been the mother of invention for a variety of products, notes Cathy Denning, senior director of safety, technology, quality assurance and regulatory affairs for Novation, an Irving, Texas-based group purchasing organization. Given Imaging's camera pill, for example, traces its roots to smart-bomb technology (Feb. 10, p. 50), and total parenteral nutrition-intravenous nutritional support-was developed out of necessity in wartime, she says.

Products move quickly from the battlefield to hospitals. Denning says Novation is working on a contract with a company called MedWave based in Danvers, Mass., for its noninvasive blood pressure monitoring system called Vasotrac. The product allows clinicians to track a seriously ill patient's blood pressure with just a bracelet. Vasotrac has been in use for about two years, but it was put to the test in the Iraq battlefields, she says. Novation is granting the contract under its new technology program. "There is no like product on the market," Denning says.

Similarly, Gregory soon can expect a call from Denning regarding the chitosan bandage.

"I am going to contact them," she says. "It's really handy, I think, to have on an ambulance."

__________________
Mr. Jan B. Wade
Blood Management Consultant
Enhance Outcomes - Control Cost
For Information Call - 360 296-1807
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