Mende Biotech and Totarol

A novel process developed by Callaghan Innovation scientists is being used to extract the antimicrobial product “totarol” from totara logs. This product is now being sold by Mende Biotech Ltd to L’Oreal for use in cosmetics. A Masterton vet is using a spray and “putty” containing totarol for topical application to combat skin diseases and wounds in domestic animals. Totarol has potential uses against mastitis and metritis in cattle and offers the possibility of an alternative to antibiotics for both animal and human use.

New Zealand’s flora is significantly different from most other land masses. The absence of mammals (other than a few bats) has meant that plants have not had to protect themselves to the same extent from browsing or having their flowers and seeds raided by squirrels and rodents. There were moas, of course, and so some plant species developed a spiky two stage growth habit to avoid being pecked to death as a juvenile. However, plants didn’t need to become acidic and therefore unpalatable to mammals, and the more alkaline content of flowers, stems and leaves has led to the presence of compounds that have many potential uses in human and animal health. Methylglyoxal in manuka honey and oil is a prime example.

Doug Mende studied the potential for biomedical compounds from NZ native plants in the early 90s and became aware of “totarol”, a component of totara that gives its timber its long-lasting qualities and is the reason totara has been used for more than a century for fence posts, railings, foundation piles, wharf piles, railway sleepers, etc.

Totarol, which is a solid, was first identified in the 1950’s, and when Doug first started investigating it in the late 90s, it was being extracted from timber, using solvents. A scientist at the CRI Industrial Research Ltd (now called Callaghan Industrial Research Ltd or Callaghan Innovation) had been looking at totarol as a potential alternative to antibiotics but had not been able to interest pharmaceutical companies in it, but Doug saw the possibilities and took it on. In 1999 he formed a company and began to characterise the solvent extract, which had more active components than just totarol. Subsequently IRL suggested using supercritical CO2 as a method for extracting the solid.

Supercritical extraction uses high pressure CO2 to extract ingredients from raw materials for use in the health, food and cosmetic industries. It was established as an industrial process by Callaghan innovation scientists Dr’s Owen Catchpole and Steve Tallon. The advantages over solvent extraction are that it leaves no solvent in the product, the CO2 can be recycled, and it gives a higher yield of a purer product that can have organic certification.

“We did some preliminary testing and the advantages we found meant that it was a no-brainer to use it from that point on,” he says.

“At that time no one had ever done extraction from wood or extraction of a solid using supercritical CO2, so Callaghan Innovation went down a very complicated path looking at how to process totarol with high-pressure extraction without blowing things up. But they were successful and we patented it, and now it has been scaled up for use by Pharmalink Extracts Ltd in Nelson.”

The new method produced an extract with a different suite of active components and Doug had to set about re-characterising the new product.

“Just working out how to produce and analyse it accurately and consistently took years and once we achieved that, we started to look for possible customers. It took about five years to get the initial work done, and then we started working with L’Oreal,” he says.

“They evaluate between 500 and 1000 new compounds each year and they have a very strict process that takes about five years and a lot of money, and then only about five or so compounds get approved, so for us to get through that process was a huge success. L’Oreal is now our biggest customer, and because we have gone through all their toxicology tests and international registrations, etc, it has given us credibility and we’ve got to the point where we can take totarol to a different level. Millions of dollars for human health research using totarol are coming out of Germany, and there should be some very interesting results from that by the end of the year.”

However, over the past few years the main focus for Doug has been animal health, particularly mastitis and metritis in cattle. Mastitis is a $260 billion problem for New Zealand alone and the antibiotics now in widespread use are becoming increasingly ineffective and need to be replaced. Doug is convinced that a totarol formulation will do the job and cites data to show that his product is 1.6 million times stronger than penicillin when tested on mastitis bacteria.

“Taking this forward will take a large investment so we need a partner who could take totarol through the whole approval process and get it onto the market. We are currently very close to signing a six-year $2 million agreement with a major animal health company,” he says.

“The potential is huge for totarol products to work just as well or better than antibiotics and iodine and to eliminate the need for them in the dairy industry. It also has wide application for companion animals.”

The raw material for totarol production is old totara logs, posts, battens, piles etc that lie around the country. Doug collects them at his premises in Carterton and periodically sends quantities to a large industrial-scale chipper in Ohope where the timber is reduced to pieces of consistent size less than 2mm. The chipped material goes to Pharmalink Extracts Ltd in Nelson for extraction of totarol, which then comes back to Carterton for shipment around the world. Doug admits that the shipping costs are large and in the fullness of time he hopes to consolidate activities at his site.

Although the L’Oreal connection has proven the value of totarol, it has not been a huge money spinner, but Doug believes the development of human and animal health products will be rewarding down the track.

Within NZ he is working with Masterton vet Heidi Ward-McGrath to develop formulations for use on domestic animals. So far they have developed an antiseptic spray and a “pet putty” for use on wounds.

Heidi has been using these products for several years and has been integrating them more and more into her practice.

“They have become a mainstay in my clinic because they work so well. We use them for quite nasty, irritated sores and eczema on skin. Often these are caused by two bacteria working in synergy but the putty is very effective as a poultice – it dries out the wound, reduces inflammation and it has a mild local anaesthetic effect.” she says.

“It is alkaline and because a lot of bacteria don’t like that environment and it cures wounds quicker than anything else I have ever used. The putty works beautifully on humans too for athletes’ foot and people who have nasty ulcers on their feet. We’ve used it for dogs with chronic ear infections, even those that have come to me for ablation surgery; we have used it on cattle around their feet, as poultices on lots of large animals, chickens for peck wounds, a guinea pig that got mauled by a rabbit; lots of uses.”

“In cases where vets haven’t been able to get control of a skin or ear infection using antibiotics we apply the putty either daily or twice a week, and within two or three weeks they are a completely different dog. They might have suffered for years and would previously have gone regularly to the vet with ear infections, but now they never have to come again.”

One of the most potent applications for the spray is with pig dogs that may arrive with heavily contaminated wounds and multiple rips that may not have been treated for days. The totarol spray deals to the infection and after a day or the wounds can be sutured. Heidi says that so far they have treated about 35 dogs and not lost one. In some cases amputation has been prevented. “Pig hunters swear by it and they now take spray bottles with them to use in the field,” she says.

“I also use it on plates, pins and screws during orthopaedic surgery. For example, on animals with open wounds with bones sticking out and quite nasty infections right through the joint, when we have to put internal pins through all of that infection. We spray everything with totarol before it goes in and all of those animals have healed. One cat I worked on recently had a severely contaminated ankle fracture wound, and a fortnight later it was running round like nothing had happened.”

The challenge for vets, says Heidi, is to find alternatives for antibiotics because of increased resistance developing and because they effectively “napalm” the body’s whole microflora. Treating a skin problem with oral or injected antibiotics destroys the natural gut flora and increases the incidence of inflammatory bowel disease. The totarol products mean that ear and skin infections can be treated topically and so complications can be avoided.

At present the spray and putty products are sold only through Heidi’s Vetcare practice in Masterton but soon both will available nationwide through Pet World stores. Heidi says she is getting bolder in the ways she is using totarol and believes that it has huge potential for a range of animal health uses.

“It’s a paradigm shift for people to realise that they don’t have to use antibiotics to treat skin infections. We have farmers trialling it on sheep, for mastitis and metritis in cattle, footrot and for chickens, rabbits, etc. I have used it on my own skin with success,” she says.

“There are wide implications for antibiotic reduction and improvement in pet health, and the fact that it comes from a NZ tree makes quite a powerful international story. It’s a very cool idea for a product.”

Pet Putty is available through your local vet or pet store via their Petware rep.   You can also contact Vetcare Masterton on 06 377-7955 with an order and credit card payment.

Small 65 g pet putty is $24.95 plus courier
Large 130g pet putty is $32.90 plus courier
Regular courier is $10, add $5.50 for rural delivery.