Pharmaceuticals from the forest industry

Pharmaceuticals from the forest industry Bjarne Holmbom Åbo Akademi Process Chemistry Centre Turku/Åbo, Finland Solander Symposium 29 March 2007 Health-promoting compounds from the forest industry Preventing diseases Ingredients for health-promoting foods Functional foods Wood tar the most important product from Finland from the 16th century to about 1850 "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” Forest industries Pulp & Paper Wood prod. Berries Needles & leaves Mushrooms Branches Xylitol Sitosterol Bark Knots • Lignans • Flavonoids • Stilbenes 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 ? 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) Sitostanol esters used in • • • • Margarine Pasta Cheese Yoghurts • Sour milk • Meat products • Spreads • Snack bars Raisio Group 1995 - Benecol competitors • Becel pro-activ / Take Control (Unilever) • Reducol (Forbes Medi-Tech, Inc. ) • Diminicol (Teriaka Ltd, Paulig) • And more The HMR lignan story MeO O O • Identified 1957 in spruce wood by Karl HO HO Freudenberg • Studied by Rainer Ekman at ÅA in the 1970´s and 1980´s • 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 OMe OH How produce HMR in large scale ? 1998 A spruce tree was felled A knot was picked out Knot The knot contained 10% by wt. of lignans !!! Heartw. Sapw. 0.1 - 5 % 6 - 29% 0.1 % 0.0 % Picea abies Lignans in HMR 70-85% of the lignans HMR from spruce knots Research at Univ. of Turku & ÅA O MeO O HO HO • Inhibits the growth of breast cancer (in laboratory tests) • Precursor to the active metabolite enterolactone (ENL) OH OMe • 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 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 oestrogendependent health problems such as menopause symptoms and osteoporosis. www.hmrlignan.com 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 Knot research at ÅA 4-29% lignans Analysis 10% lignans ! More spruce knots Knots from other tree species Technical sep. of knots 60+ species 5-15% polyphenols Patent ”ChipSep” Pilot plant Farm plant 1998 Prep. isolation & purification 20+ pure phenols in g-amounts Fundamental chemistry Applications New structures New reactions HMR from spruce knots Techn. antiox. & biocides In other tree species other lignans ! O MeO O HO HO OH Me O O O MeO O HO HO OH OMe OMe OH O Me OH OH HMR Me O OH OH HO N o rtra ch e lo g e n in O MeO O HO Lariciresinol O Me OMe OH OH In many species also flavonoids and stilbenes S ecoisolariciresinol Matairesinol Knots: the richest source of polyphenols in nature More lignan products ? • • • • Functional foods Cosmetics (sun lotions) Technical antioxidants Natural biocides 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 Stilbenes both in knots and bark OH OH OH HO OH HO HO OH OH Piceatannol (Spruce bark) Resveratrol (Red wine & Spruce bark) Pinosylvin (Pine knots) Spruce bark: stilbenes and tannins Spruce bark waste in Finland ~ 700,000 t/a Spruce bark Residue Sequential Extraction Tannins 10-20% Carbohydrates 10-20% Stilbenes 5-10% Pycnogenol • • • • Water extract of maritime pine bark ”Nature´s super antioxidant” Procyanidins and bioflavonoids (polyphenols) Good for – – – – – Cardiovascular health Skincare Diabetes health Inflammation Among others --- Galactoglucomannans (GGM) from TMP effluents TMP Wood-cont. papers GGM conc. Ultrafiltration Effluent treatment Surface modification Food ingredient Emulsifier O-acetyl-galactoglucomannans (GGM) CH2OH OH CH2OH O O A OH O- c OH O O OH O OH OH O CH2 OH O O OH O Ac OH O O CH2OH O OH O CH2OH CH2OH OH DP ~ 100 - 300 Lines to value-added natural healthy products Xylitol Sitosterol / Sitostanol Pulping TMP effl. Papermaking Glucomannans Lignans Flavonoids Stilbenes Paper Board “Dietary fibre” Knots Bark Stilbenes Tannins Dietary supplements Health-prom. foods. Techn. Antioxidants Natural biocides 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 Specialty Chemicals from Trees • Complicated structures, not easily synthesized by chemists • Synthesized elegantly by Nature • Contain much of ”Nature´s Wisdom” • Truly ”green” chemicals • Small volumes, but ”healthy” margins 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 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 • University of Turku – Rainer Sjöholm, Patrik Eklund, Annika Smeds – Risto Santti, Sari Mäkelä, Niina Saarinen, Markku Ahotupa • Personnel at Hormos Medical and UPM-Kymmene