Microsoft Word 夏建华.doc

Transcription

1 5 7 Vol. 5 No Journal of Food Safety and Quality Jul., 2014 * 夏建华 (, ) 摘要 :,, :,,, 70, 关键词 : ; ; ; Application of proteases as natural health products XIA Jian-Hua * (Beijing Wisapple Biotech Co., Ltd, Beijing China) ABSTRACT: Proteases are inseparable from our daily life. Their roles cover many aspects of cell cycles, metabolic regulations and body defenses. Actions of proteases consist of breaking down food proteins, assisting to decompose dying cells, neutralizing invading living agents or proteins and producing functional peptides which promote healings, to ensure a balanced cycling of metabolism and life. In the western countries, the history of using hydrolytic enzymes and protease included, as digestive aids could be traced back to at least 70 years ago. In contrast, the main stream of natural proteolytic enzymes which can be mass-produced in China has not yet been listed as ingredient for natural health products or dietary supplements. This paper briefly presents the characteristics, main functions, safety of application and the world market situation of several types of proteases. Application of proteases as natural health products seems to be promising in China. KEY WORDS: food enzyme; protease; dietary supplement; natural health product 1 引言,,, [1] 1930, 30, 1993, , 150, [2], [2-3],,, [2-3], * 通讯作者 :,,, jhxia@wisapple.com *Corresponding author: XIA Jian-Hua, PhD, Beijing Wisapple Biotech Co., Ltd. No.6 Yard, Jinxing West Road, Huangcun, Daxing District, Beijing, , China. jhxia@wisapple.com

2 7 : 1991 [2-4], 1948 [5-6] 50,,,,, [2] : 2015,, 20%,, :,, [11-12], [13] 1-A: Fig.1-A: Blood clot was induced in a rabbit ear 2 蛋白酶的作用机制及功能 2.1 作用机制,,,,, [7],, [3] (Arg) (Lys) Arg Lys, [8] : ;,,,, [2,4,9], (plasminogen), - (plasmin), 1 Innerfield 1952 : 24 [10] 1-B: 24, Fig. 1-B: 24 hours after a trypsin infusion, the clot was dissolved Fig. 1 1 [10] Histologic sections of experimentally produced rabbit ear vein thrombus dissolved by trypsin [10] 2.2 不同来源蛋白酶的理化特性, 1, 3 蛋白酶的保健应用 3.1 应用历史,,,, [2],

3 Table 1 表 1 蛋白酶的理化特性 Physical & chemical characteristics of proteases EC number, Da ph: 7.8~8.5,, ph: 8.0~9.0, ph: 6.0~7.0 : 55~65,, (-SH) ph: 6.0~8.0 : 55 (-SH) ph: 5.7 : 65, ph: 7.0~9.0 : 50, ph: 10.0 : 42,,, [14-17] 1965, [2] , 95% 2008 :,, [2] 19,, 100 (ETA) [18], (digestive aid) 70, 90 (dietary supplement) 20 [18], [19], [12, 20-23], 3.2 不同来源的蛋白酶作用的特点 (1) [7-8],,,,,,, 60 Mucos,, (cystic fibrosis) [19] (2) [24] 1957, [25], [12, 16, 20-22, 26],

4 7 : 1993 (3) [27],, GB ( ) [28] [29-30], [9] (4), [31], NK-CP 1987, [32], [13-15], [23, 33-35],,, [36-37], (5) 19 60,,,, [38-39] 3.3 多种类酶或有机活性成分的整合使用 : [40-42],,,,,,, Wobenzyme, Vitalzym, Puritan s Pride,,, Wobenzyme 1957,,, 1960 Wobenzym N,, Wobenzym N : 300 mg; 72 mg; 3 mg; 180 mg; 135 mg; 150 mg 1999, Wobenzym Life Enhancement SmartZyme : 70 mg, 12 mg, 32 mg, 100 mg, 600 mg,,,,, 4 市场趋势 1994, 3500, 4700, , 100, , 2.5 [18] BCC Research [43] : , 39, , (CAGR) : 2011, 12, , 13, , 15, [22] 40% [29],, [37], Mucos, Specialty Enzyme,, 2,

5 Table 2 表 2 国内天然蛋白酶原料主要生产厂家 Main manufacturers of natural protease ingredients in China // / / / / // / / / 5 安全性,, (autolysis), [2],, ( ), ( ), 40, [18] FDA 21CFR 184 (GRAS) [44] GRAS GRAS GMP [45, 46], [47], [46], ETA, , 46, 14,, 90%, [18] 6 结束语,,,,,,,,,,,, 致谢 : 感谢刘静 杨滢 刘天岩 康进在本文准备工作中的帮助 参考文献 [1]. [M]. :, 2011: Wu WT. Pharmacology of enzymes [M]. Beijing: China Medical Science Press, 2011: [2],. [J]., 2008, 04:

6 7 : Hu XZ, Wang J. Advances in protease production and application [J]. Ind Microbiol, 2008, 04: [3] Sumantha A, Larroche C, Pandey A. Microbiology and industrial biotechnology of food-grade proteases: a perspective [J]. Food Technol Biotechnol, 2006, 44(2): [4] Kaur R, Sekhon BS. Enzymes as drugs: an overview [J]. J Pharm Educ Res, 2012 Dec, 3(2): [5] Howell E. The status of food enzymes in digestion and metabolism. The national enzyme company 1946 [EB/OL]. org/wp-content/uploads/2012/04/orally-administered-enzyme-food-supp lement-safety-overview1.pdf. [6] Jones J. Medical Economics Inc, Physician s Desk Reference, 1948 [EB/OL]. Orally-Administered-Enzyme-Food-Supplement-Safety-Overview1.pdf. [7] Wikipedia. Serine protease [EB/OL]. protease. [8] Wikipedia. Trypsin [EB/OL]. [9] Gomes FS, Spinola CV, Ribeiro HA, et al. Wound-healing activity of a proteolytic fraction from Carica candamarcensis on experimentally induced burn [J]. Burns. 2010, 36(2): [10] Innerfield I, Schwarz A, Angrist A. Intravenous trypsin: its anticoagulant, fibrinolytic and thrombolytic effects [J]. J Clin Invest, 31: [11] Metzig C, Grabowska E, Eckert K, et al. Bromelain proteases reduce human platelet aggregation in vitro, adhesion to bovine endothelial cells and thrombus formation in rat vessels in vivo [J]. In Vivo, 1999, 13(1): [12] Maurer HR. Bromelain: biochemistry, pharmacology and medical use [J]. Cell Mol Life Sci, 2001, 58(9): [13] Sumi H, Hamada H, Nakanishi K, et al. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase [J]. Acta Haematol. 1990, 84(3): [14] Fujita M, Hong K, Ito Y, et al. Transport of nattokinase across the rat intestinal tract [J]. Biol Pharm Bull, 1995, 18(9): [15] Yang NC, Chou CW, Chen CY, et al. Combined nattokinase with red yeast rice but not nattokinase alone has potent effects on blood lipids in human subjects with hyperlipidemia [J]. Asia Pac J Clin Nutr, 2009, 18(3): [16] Castell JV, Friedrich G, Kuhn CS, et al. Intestinal absorption of un-degraded proteins in men: presence of bromelain in plasma after oral intake [J]. Am J Physiol, 1997, 273(1 Pt 1):G [17] Hsia CH, Shen MC, Lin JS, Wen YK, et al. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects [J]. Nutr Res, 2009, 29(3): [18] Enzyme Technical Association. Orally administered enzyme food supplement safety overview [EB/OL]. Safety-Overview1.pdf. [19] Roxas M. The role of enzyme supplementation in digestive disorders [J]. Altern Med Rev, 2008, 13(4): [20] Kelly GS. Bromelain: a literature review and discussion of its therapeutic applications [J]. Altern Med Rev, 1996, 1(4): [21] Walker AF, Bundy R, Hicks SM, et al. Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults [J]. Phytomedicine, 2002, 9(8): [22] Klein G, Kullich W, Schnitker J, et al. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs [J]. Clin Exp Rheumatol, 2006, 24(1): [23] Suzuki Y, Kondo K, Ichise H, et al. Dietary supplementation with fermented soybeans suppresses intimal thickening. [J]. Nutrition, 2003, 19(3): [24] Wikipedia. Bromelain [EB/OL]. [25] Neubauer RA. A plant protease for potentiation of and possible replacement of antibiotics [J]. Exp Med Surg. 1961, 19: [26] Hale LP, Chichlowski M, Trinh CT, et al. Dietary supplementation with fresh pineapple juice decreases inflammation and colonic neoplasia in IL-10-deficient mice with colitis [J]. Inflamm Bowel Dis, 2010, 16 (12): [27] Wikipedia. Papain [EB/OL]. [28], GB [S]. National food safety standard, GB Standard for uses of food additives [S]. [29] Abhijit R. Protease enzyme-potential industrial scope [J]. Eng Res, 2012, 2(1):1 5. [30],,. [J]., 2010, 141(11): Zhao DB, Chen X, Zhang L. Advances in extraction and application of papain [J]. Meat Res, 2010, 141(11): [31] Wikipedia. Nattokinase [EB/OL]. [32] Sumi H, Hamada H, Tsushima H, et al. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet [J]. Experientia, 1987, 43(10): [33] Kim JY, Gum SN, Paik JK, et al. Effects of nattokinase on blood pressure: a randomized, controlled trial [J]. Hypertens Res, 2008, 31(8): [34] Fujita M, Ohnishi K, Takaoka S, et al. Antihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive rats [J]. Biol Pharm Bull, 2011, 34(11): [35] Murakami K, Yamanaka N, Ohnishi K, et al. Inhibition of angiotensin I converting enzyme by subtilisin NAT (nattokinase) in natto, a Japanese traditional fermented food [J]. Food Funct, 2012, 3(6): [36],. [J]., 2010, 221(8): Liu L, Peng XC. Characteristics of Douchi fibrinolysin and Nattokinase: a comparison [J]. Chin Brewing, 2010, 221(8): [37],. [J]., 2011, 36(4): Lu L, Suo HY. Advances in Douchi fibrionlysin research [J]. China Condiment, 2011, 36(4): [38] Kaplan JB. Biofilm dispersal: mechanisms, clinical implications, and potential therapeutic uses [J]. J Dent Res, 2010, 89(3): [39] Artini M, Papa R, Scoarughi GL, et al. Comparison of the action of different proteases on virulence properties related to the staphylococcal surface [J]. J Appl Microbiol, 2013, 114(1): [40] Wittenborg A, Bock PR, Hanisch J, et al. Comparative epidemiological study in patients with rheumatic diseases illustrated in an example of a treatment with non-steroidal anti- inflammatory drugs versus an oral en-

7 zyme combination preparation [J]. Arzneimittel-Forsch, 2000, 50(8): [41] Akhtar NM, Naseer R, Farooqi AZ, et al. Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee-a double-blind prospective randomized study [J]. Clin Rheumatol, 2004, 23(5): [42] Roep BO, Van den Engel NK, Van Halteren AG, et al. Modulation of autoimmunity to beta-cell antigens by proteases [J]. Diabetologia, 2002, 45(5): [43] BCC Research. Global Markets for Enzymes in Industrial Applications [EB/OL]. enzymes-industrial-applications-markets-bio030g.html. [44] U.S. Food and Drug Administration, CFR Title 21 database [EB/OL]. Part 184. [45] Health Canada, Food & Nutrition, Food safety, List of Permitted Food Enzymes (Food Additives) [EB/OL]. addit/list/5-enzymes-eng.php. [46] Health Canada, Drugs & Health Products, Natural Health Products Ingredients Database [EB/OL]. search-recherchereq.do?lang=eng. [47] Association of Manufacturers and Formulators of Enzyme Products. List of Commercial Enzymes [EB/OL]. g/files/g412356/f/201404/amfep-enzymes-list-april-2014_0.pdf. 作者简介 ( 责任编辑 : 杨翠娜 ) 夏建华, 博士, 研究方向为生物技术应用, 酶和小分子物的工业规模制备纯化 jhxia@wisapple.com 食品掺假研究 专题征稿,, tougao@chinafoodj.com 食品安全质量检测学报 编辑部