In the 1950s, under the leadership of then-President Yuji Ito, four researchers were sent to
research institutes in the West, where science and technology were more advanced, for several years.
Tomio Nishihara was sent to the laboratory of Professor Paul Mead Doty at Harvard University in the
United States for two and a half years in 1956, and Tadahiko Fujii was sent to the laboratory of Dr.
Klaus Kühn at the Max Planck Institute in Germany. At the time, the details of the protein collagen
were not yet known, and it was found that only a few percent of the collagen in animal tissue could
be dissolved, and this was called soluble collagen at the time. Nishihara returned to Japan after
conducting research on soluble collagen in the Doty laboratory.
Until the successful extraction of collagen by Dr. Tomio Nishihara in 1960, collagen was thought to
be an insoluble protein, and it was thought that there was no effective method of dissolving it
other than boiling it down as gelatin. However, when heat is applied, the triple-helix structure
that collagen maintains in the body is destroyed. Dr. Nishihara came up with the idea of using
protein-digesting enzymes such as trypsin, pancreatin and pepsin to solubilize the protein, and
succeeded in obtaining most of the collagen in a dissolved state while maintaining its original
structure. This new collagen solubilization method was patented in 1963, after a patent application
was submitted in 1960, and was also granted a US patent [References 1 and 2]. It was also published
in a paper entitled “Enzymatic Action on Collagen and the Structure of Insoluble Collagen Fibrils”
[Reference 3].
Dr. Nishihara moved to the United States again in 1966, and in order to develop basic research on
collagen into industry, he went to the Rogosin Laboratory at Cornell University, which was at the
forefront of research into artificial organs at the time, and joined Albert Rubin's laboratory, but
he passed away in December 1967.
Starting with the invention of this first collagen solubilization method, Japan Leather Co., current
Nippi Research Institute of Biomatrix, developed various collagen solubilization methods, and in
particular, the alkaline solubilization method invented by Dr. Tadahiko Fujii [references 4 and 5]
was applied to the production of Cosmetic Skin Care Cream (now: Skin Care Gel NM Balance) by our
sister company, Nippi Collagen Cosmetics, Ltd.
In addition, by making full use of collagen solubilization technology and collagen re-fibrillation
technology, we have been conducting research into the application of collagen for medical use, and
have developed products such as artificial skin, surgical sutures, and artificial dialysis
membranes. This technology has been passed on to our collagen casings and collagen products for
research use.
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