The Changes of Fibrinolytic Activity of Nattokinase in Artificial Gastrointestinal Environment and Human Digestive Juice

Abstract:

Article Preview

Purpose: To search for the change of fibrinolytic activity of different forms of nattokinase when they were treated in human digestive juice, artifical gastric and intestinal juice differently, and to lay the foundation of a proper pharmaceutical dosage form of nattokinase. To provide direct evidences that Nattokinase products can be administered orally and to screen a suitable dosage form for oral administration of nattokinase.Methods: The non-crushed sample was prepared through the solid fermentation of soybean meal at 37°C for 36 h, and evaporation at 70°C for 8 h, The fine and ultra-fine powder were gotten from the non-crushed sample by the micronizer and ultra micronizer. Nattokinase extract was the supernatant liquid of 0.9% saline of non-crush samples. The nattokinase’s fibrinolytic activity of non-crushed sample, fine powder, ultra-fine powder and extract treated in artifical and human digestive were measured by the Fibrin plate method. Results: Three kind of solid form samples still remain about 80% fibrinolytic activity in artificial gastric juice for 4 h, and the fibrinolytic activity of nattokinase extract is 48.7% at the end of treatment. Treated in artificial gastric juice for 4 hours, then handled in artificial intestinal fluid for 4 h, the final fibrinolytic activity of fine and ultra fine powder is 47.0% and 51.0%. The fibrinolytic activity of extract is 79.8% at the end of treatment in human digestive juice for 4 h. At the beginning of treatment in human digestive juice the enzyme activity of fine and ultra fine powder is 130.8U/mL and 132.1U/mL, however, after treatment for 4 h the enzyme activity is 158.7U/mL and159.6U/mL, which is near to the total enzyme activity of sample. Conclusion: Nattokinase products can be administered orally, and solid preparations of nattokinase are more suitable for oral route. The optimum dosage form for oral administration of nattokinase is enteric-coated capsules containing ultra fine powder.

Info:

Periodical:

Advanced Materials Research (Volumes 581-582)

Edited by:

Jimmy (C.M.) Kao, Wen-Pei Sung and Ran Chen

Pages:

1145-1150

Citation:

Y. L. Zhao et al., "The Changes of Fibrinolytic Activity of Nattokinase in Artificial Gastrointestinal Environment and Human Digestive Juice", Advanced Materials Research, Vols. 581-582, pp. 1145-1150, 2012

Online since:

October 2012

Export:

Price:

$38.00

[1] Prafulla M. Mahajan, Sagar V. Gokhale, and Smita S. Lele. Production of Nattokinase Using Bacillus natto NRRL 3666: Media Optimization, Scale Up, and Kinetic Modeling, J, Food Sci. Biotechnol. 19(2010)1593-1603.

DOI: https://doi.org/10.1007/s10068-010-0226-4

[2] Sumi H, Hamado H, Tsushima H, Mihara H, Murica H. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese natto: a typical and popular soybean food in the Japanese diet, J, Experientia. 43 (1987)1110–1111.

DOI: https://doi.org/10.1007/bf01956052

[3] Fujita M, Hong K, Ito Y, Misawa S, Takeuchi N, Kariya K, Nishimuro S. Transport of nattokinase across the rat intestinal tract, J, Biol. Pharm. Bull. 18(1995): 1194–1196.

DOI: https://doi.org/10.1248/bpb.18.1194

[4] Fujita M, Hong K, Ito Y, Fujii R, Kariya K, Nishimuro S. Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat, J, Biol. Pharm. Bull. 18(1995) 1387–1391.

DOI: https://doi.org/10.1248/bpb.18.1387

[5] Chang CT, Fan MH, Kuo FC, Sung SY. Potent fibrinolytic enzyme from a mutant of Bacillus subtilis IMR-NK1, J, Agr. Food Chem. 48 (2000)3210-3216.

DOI: https://doi.org/10.1021/jf000020k

[6] Urano T, Ihara H, Umemura K. The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis cleaves and inactivates plasminogen activator inhibitor type-I, J, Biol. Chem. 276 (2001)24690- 24696.

DOI: https://doi.org/10.1074/jbc.m101751200

[7] Sumi H, Hamada H, Nakanishi K, Hiratani H. Enchancement of the fibrinolytic activity in plasma by oral administration of nattokinase. J, Acta Haematol. 84(1990)139–143.

DOI: https://doi.org/10.1159/000205051

[8] Natto experical research institute, Natto experiment, Tokyo, (1990).

[9] Onesmus K. Ashipala, Qian He. Optimization of fibrinolytic enzyme production by Bacillus subtilis DC-2 in aqueous two-phase system (poly-ethylene glycol 4000 and sodium sulfate), J, Bioresource Technology. 99 (2008)4112–4119.

DOI: https://doi.org/10.1016/j.biortech.2007.09.029

[10] M. Fujita, K. Nomura, K. Hong, et al. Purification and Characterization of a Strong Fibrinolytic Enzyme (Nattokinase) in the Vegetable Cheese Natto, a Popular Soybean Fermented Food in Japan, J, Biochemical and Biophysical Research Communications. 197(1993).

DOI: https://doi.org/10.1006/bbrc.1993.2624

[11] Astrup T S, Mullertz S. The fibrin plates methods for estimating fibrinolytic activity, J, Arch Biotech Biophys. 40 (1995) 346-351.

[12] Sumi H. Antibacterial Activity of Bacillus natto-Growth inhibition againse Escherichia coli 0157, J, Bioindustry. 14 (1997) 47.