HISTORY OF LYPRINOL^®

Pharmalink is the beneficiary and owner of more than 27 years of experience and research on perna canaliculus, the New Zealand green lipped mussel, culminating in the development of Lyprinol®. This pioneering work was led by the MacLab group who are both investment and business partners of the Company.

The development of Lyprinol® can be traced back to 1973 when the MacLab group first acquired an interest in certain mussel farming operations and set out to develop New Zealand green lipped mussel extract as a natural treatment for arthritis.

In 1975 the MacLab group formed a joint venture to market a freeze dried mussel powder extract. The partners established a new company in Australia to run the venture and registered the new product’s name "Seatone" worldwide.

The first markets for Seatone were in Australia and New Zealand. The UK market opened soon afterwards. The product generated enormous publicity with excellent sales occurring in the United Kingdom where arthritis is a major problem. The medical profession, however, took a negative view of the product. There was an attempt by some members of the profession to discredit Seatone, as was done previously in respect of other natural health products.

Several clinical studies were started with a view to proving the anecdotal evidence that the mussel extract was beneficial as a natural anti-arthritis remedy. Two small studies, each with statistically unacceptably small numbers, found the extract to be of no value. These studies became tools for opponents of the product in their endeavors to discredit it. Then in 1978, Drs. Sheila and Robert Gibson, a husband and wife medical team working in the public health system in Glasgow, Scotland, undertook a major study. Their results, published in The Practitioner in 1980, clearly indicated that the mussel extract was of substantial value as a front line treatment for certain forms of arthritis. A flurry again followed the publication of these results. The MacLab group came under attack from some sections of the medical community who seemed determined to have the product banned.

In 1982 the MacLab group, in partnership with a United Kingdom group, purchased a mussel powder factory in New Zealand and immediately established a research project at the Natural Products Chemistry Division of the Royal Melbourne Institute of Technology University, in Australia. ("RMIT").

The group’s initial aim was to develop hard scientific evidence showing that a naturally occurring anti-inflammatory compound existed in the mussel, without relying on clinical studies of the unstabilized mussel powder whose results had proven to be unreliable. This work was funded for a two year period and then reviewed.

In 1983 the Maclab group's Jim Broadbent, on a visit to Japan, met Japan’s foremost authority on natural products chemistry, Professor Takuo Kosuge, who at that time was Professor of Pharmacology at the Shizuoka University in Shizuoka City, Japan. Professor Kosuge knew of the New Zealand mussel extract from a friend. He was so intrigued by the research project that he offered the collaboration of his research group to the RMIT scientists in the further study of the mussel. The RMIT scientists were confident that they were on track to finding the active lipids in the mussel. They set about establishing a method of isolating the active fractions by using the leading technology in the field, high performance liquid chromatography ("HPLC"). Notwithstanding their best efforts, they found these fractions still almost impossible to isolate even though work progressed over several years.

The RMIT scientists discussed their problems with Professor Kosuge who ran his own series of tests but who also failed to isolate the active fractions. Professor Kosuge concluded that because the basic mussel powder was extremely unstable meaning it oxidized rapidly, until this problem could be overcome, the future of its research and the development of the therapeutic value of the product in general would remain in doubt. Unless stabilization could be achieved, the project would come to an end. Unstabilized mussel powder could not guarantee a proven benefit because its oxidization eliminated most of its potent activity over time. Therefore, clinical research could never be undertaken on unstabilized mussel powder because one could never rely on the mussel powder’s consistent level of activity.

Professor Kosuge set about establishing a screen to check the activity of different batches of mussel powder. He found an enormous variation in activity. He also discovered that this activity quickly deteriorated when a combination of heat and moisture was present. He experimented with all the recognized anti-oxidants as stabilizers but without success. Finally he turned to research work that he had conducted some twenty years earlier. This research had identified the ancient technique used by traditional Japanese fishermen to store fish in a special solution, which preserved the fish for years.

Professor Kosuge tested a variation of this solution on the mussel flesh and the result was quite spectacular : The oxidization was arrested ! The MacLab group patented this process and, along with making other major changes to the production process, finally produced a vastly superior stabilized mussel extract product.

Stabilizing the mussel powder was a major breakthrough. This meant that its anti-inflammatory activity could be maintained without the risk of oxidization. Having finally achieved a stabilized mussel powder with standardized and consistent activity, scientists were able to conduct realistic clinical research giving measurable and repeatable results. This difference between the potency of stabilized and unstabilized mussel powder was borne out by Dr. Michael Whitehouse’s comparative study of the anti-arthritis inflammation activity of both stabilized and unstabilized mussel powders in 1997. The study showed dramatic results of 90% and 14%, respectively, for the two mussel powders’ inflammation reduction activity.

The RMIT scientific group began to successfully extract selected lipids from the mussels which they believed held the beneficial activity. They did this no longer encountering the problem of oxidization of the mussel powder.

The MacLab group believed that the New Zealand manufacturing base needed to be upgraded urgently to introduce this new process. However, unable to reach agreement with its partners, the MacLab group sold their manufacturing interests and the "Seatone" trademark for all countries except Australia, Japan and some South East Asian markets to their United Kingdom partners in 1986.

The MacLab group’s principal aim then became research into the isolation of the potent active principle from the mussel extract. The MacLab group’s plan was to establish a new, more effective product under a different brand name, while still continuing to sell the stabilized mussel powder in Australia and Japan under the "Seatone" name. The MacLab group’s former partners in the United Kingdom continued to sell unstabilized mussel powder under the "Seatone" brand name in European markets. This has led to some confusion about which product was the "active" (stabilized) Seatone and which Seatone product unstabilized was not. For this reason, Dr. Michael Whitehouse and others in their past research have been critical of (unstabilized) mussel powder.

In 1992 the MacLab group enlisted the help of Dr. Henry Betts, Principal Scientist at the Rheumatology Research Laboratory, The Queen Elizabeth Hospital, in Adelaide, the teaching hospital attached to the Department of Medicine at Adelaide University in South Australia. Dr. Betts had previously established an in vitro method of testing anti-inflammatory compounds. He agreed to test the fractions that the RMIT scientists had extracted. To the delight of the scientists involved, Dr. Betts advised them that two of these fractions were the most active compounds he had ever examined in his testing system. Unfortunately, they were not pure and he was unable to identify them. His work continued for 18 months. As the RMIT scientists purified each fraction further, Dr Betts tested each one.

Dr. Betts suggested that an in vivo test be carried out. He introduced the MacLab group to Dr. Michael Whitehouse, an internationally acclaimed expert in the testing of compounds for anti-inflammatory activity in laboratory animals. Dr. Whitehouse agreed to become involved and commenced laboratory animal studies in 1994. His in vivo laboratory animal results confirmed the activity that Dr. Betts had shown in his in vitro testing. Having identified the area in which the activity existed, the next question was how these lipids could be extracted commercially without damaging the active compounds. It took a further two years of intensive testing to develop the protocols for the super critical fluid extraction (SFE) process which has now been patented by the Company. This process utilizes liquefied carbon dioxide and does not use any chemical solvents.

International Patents

As a result of this work international patents have been applied covering the following:

Stabilization
The stabilization of the active Lipids in the mussel prior to oxidation.

Active Fractions
The isolation of groups of active fractions within the mussel powder.

Extraction process
This extraction process allows the lipid to be extracted without chemical residues.

Usage
For Lyprinol® to be used as an anti-inflammatory product for the applications of Arthritis, Asthma and other pending applications.

Over the years of research on the New Zealand green lipped mussel there have been many stages of achievement but none compare with the greatest breakthrough... The discovery of the pure anti inflammatory fraction we call Lyprinol®.