Pharmaceuticals from the forest industry

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Pharmaceuticals from the forest industry

• Bjarne Holmbom
• Åbo Akademi
• Process Chemistry Centre
• Turku/Åbo, Finland

Solander Symposium 29 March 2007
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Health-promoting compoundsfrom the forest
industry
Preventing diseases Ingredients for
health-promoting foods Functional foods
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Wood tar the most important product from
Finland from the 16th century to about 1850
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• "Jos ei sauna, terva ja viina auta, niin tauti on
  kuolemaksi."
• If sauna, tar and vodka do not cure your
  disease, then you will die

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Forest industries
Pulp Paper Wood prod.
Berries Mushrooms
Needles leaves Branches
Xylitol Sitosterol
Bark Knots

• Lignans
• Flavonoids
• Stilbenes

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Xylitol

• Natural sweetener with a cool taste
• Inhibits tooth decay (Univ. of Turku 1970s)
• Also inhibits ear infections in children
• One of the first functional foods
• Production in Kotka, Finland since 1975
• Xylitol chewing gum, Hellas Turku 1975
• Production world-wide ? 30000 50000 ton/a ?

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Sitosterol/Sitostanol

• Inhibit cholesterol from being absorbed into the
  blood stream
• Reduce "bad" cholesterol (LDL) typically by
  10-20
• Sitosterol extracted from tall oil soap or tall
  oil pitch
• Sitosterol production in Finland 1980 2005
• New sitosterol plant producing 4000-6000 t/a in
  Rauma announced (company Forchem)

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Sitostanol esters used in

• Margarine
• Pasta
• Cheese
• Yoghurts

• Sour milk
• Meat products
• Spreads
• Snack bars

Raisio Group 1995 -
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Benecol competitors

• Becel pro-activ / Take Control (Unilever)
• Reducol (Forbes Medi-Tech, Inc. )
• Diminicol (Teriaka Ltd, Paulig)
• And more

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The HMR lignan story

• Identified 1957 in spruce wood by Karl
  Freudenberg
• Studied by Rainer Ekman at ÅA in the 1970s and
  1980s
• Pure HMR prepared 1991 for prof. Risto Santti at
  Univ. of Turku
• Expected estrogenic effects not found
• But - - - HMR was found to inhibit growth of
  breast cancer cells
• Hormos Medical Ltd came in

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How produce HMR in large scale ?
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1998 A spruce tree was felled A knot was picked
out
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Knot
The knot contained 10 by wt. of lignans !!!
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Heartw. Sapw.
6 - 29
0.0
0.1
0.1 - 5
Lignans in Picea abies
HMR 70-85 of the lignans
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HMR from spruce knots

• Research at Univ. of Turku ÅA
• Inhibits the growth of breast cancer
• (in laboratory tests)
• Precursor to the active metabolite enterolactone
  (ENL)
• Strong antioxidant
• Hormos Medical Inc., Turku 1997 -
• US-FDA approval as dietary supplement in May
  2004
• Linnea S.A., Locarno, world-wide production and
  marketing license

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On the market In 2006
Recent research has shown that plant lignans
have a positive influence on the development of
breast, prostate and colon cancer which rely
specifically on oestrogens in order to progress.
Lignans also help to maintain good
cardiovascular health and to moderate other
oestrogen-dependent health problems such as
menopause symptoms and osteoporosis.
www.hmrlignan.com
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Paper mill in Northern Finland
Spruce chips
Farm in Southern Finland Separation of pure knots
Pure knot material
Linnea SA, Locarno Extraction and purification
HMR in capsules
Dietary supplement markets
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Knot research at ÅA
4-29 lignans
More spruce knots
Analysis 10 lignans !
Knots from other tree species
60 species 5-15 polyphenols
Patent ChipSep
Technical sep. of knots
Pilot plant
Farm plant
Prep. isolation purification
20 pure phenols in g-amounts
1998
Fundamental chemistry
New structures New reactions
HMR from spruce knots Techn. antiox. biocides
Applications
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In other tree species other lignans !
HMR
In many species also flavonoids and stilbenes
Matairesinol
Knots the richest source of polyphenols in nature
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More lignan products ?

• Functional foods
• Cosmetics (sun lotions)
• Technical antioxidants
• Natural biocides

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HMR already in food

• Recent study at Åbo Akademi
• Smeds, A., Eklund, P., Sjöholm, R., Willför, S.,
  Nishibe, S., Deyama, T. and Holmbom, B. (2007)
  Quantification of a broad spectrum of lignans in
  cereals, oilseeds and nuts. J. Agric. Food Chem.
  55 117-1346.
• HMR a major lignan in both wheat and rye bran
• 2.8 mg/100 g in wheat bran
• 1.0 mg/100 g in rye bran
• HMR concentration in spruce knots, typically
• 4-8 4000 8000 mg/100 g

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Stilbenes both in knots and bark
Resveratrol (Red wine Spruce bark)
Pinosylvin (Pine knots)
Piceatannol (Spruce bark)
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Spruce bark stilbenes and tannins
Spruce bark waste in Finland 700,000 t/a
Spruce bark
Residue
Sequential Extraction
Stilbenes 5-10
Tannins 10-20
Carbo- hydrates 10-20
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Pycnogenol

• Water extract of maritime pine bark
• Natures super antioxidant
• Procyanidins and bioflavonoids (polyphenols)
• Good for
• Cardiovascular health
• Skincare
• Diabetes health
• Inflammation
• Among others ---

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Galactoglucomannans (GGM)from TMP effluents
Wood-cont. papers
TMP
GGM conc.
Ultra- filtration
Surface modification Food ingredient Emulsifier
Effluent treatment
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O-acetyl-galactoglucomannans (GGM)
DP 100 - 300
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Lines to value-added natural healthy products
Xylitol Sitosterol / Sitostanol
Paper Board
Pulping
Papermaking
TMP effl. Glucomannans Dietary fibre
Lignans Flavonoids Stilbenes
Dietary supplements Health-prom. foods. Techn.
Antioxidants Natural biocides
Knots
Stilbenes Tannins
Bark
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Trees are different plants

• Live very long
• Contain high concentrations of protecting defense
  substances
• Created by natural evolution during millions of
  years
• Rich sources of a wide variety of bioactive
  substances

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Specialty Chemicals from Trees

• Complicated structures, not easily synthesized by
  chemists
• Synthesized elegantly by Nature
• Contain much of Natures Wisdom
• Truly green chemicals
• Small volumes, but healthy margins

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Major financial support

• Academy of Finland (Finnish Centre of Excellence
  Programme)
• Tekes (Finnish Funding Agency for Technology and
  Innovations)
• Keksintösäätiö (Foundation for Finnish
  Inventions)
• Hormos Medical
• UPM-Kymmene

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Team Work

• ÅA, Wood and Paper Chemistry
• Rainer Ekman (), Markku Reunanen, Christer
  Eckerman, Jarl Hemming, Andrey Pranovich, Lari
  Vähäsalo, Stefan Willför, Kenneth Sundberg, Suvi
  Pietarinen, Linda Nisula, Thomas Holmbom, Reija
  Harlamow
• ÅA, Organic Chemistry
• Rainer Sjöholm, Patrik Eklund, Annika Smeds
• University of Turku
• Risto Santti, Sari Mäkelä, Niina Saarinen, Markku
  Ahotupa
• Personnel at Hormos Medical and UPM-Kymmene