- NKCP is extracted from Bacillus subtilis natto and it is free of the undesirable odor and viscous texture of natto.
- NKCP's purpose is three-fold. To function as (1) an anticoagulant (2) thrombolytic and (3) decreases blood viscosity.
- The majority of the vitamin K2 has been eliminated, therefore it is less antagonistic to other drugs such as warfarin.
- NKCP has been adjusted to contain a fixed amount of functional protein, Bacillopeptidase.
- The principal functional enzyme (protease) is stable at pH 6.0-10.0 and at temperatures 60℃ or below.
- The safety of NKCP has been confirmed in many animal and human studies.
- The production process for this purified filtrate of Bacillus subtilis natto culture is registered under Patent No. 3532503 in Japan.
【Dose Recommendation】
Based on animal and human studies, 125 to 500mg is the daily recommended dose of NKCP.
【Safety Studies】
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Single-dose toxicity (rats)
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LD50＞5,000mg/kg
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Repeated-dose toxicity (rats), 90 days
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NOAEL
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Males: > 1,325mg/kg body weight/day
Females: > 1,541mg/kg body weight/day
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Mutagenicity
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Negative (± metabolic activation)
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Antigenicity (guinea pigs)
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Negative for active systemic anaphylactic reaction (ASA) and passive cutaneous anaphylactic reaction (PCA)
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Effect on bleeding time (rats)
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In rats orally given NKCP, a 0.5mm incision was made in the tail tip after 1 hour to measure bleeding time. NKCP at 300mg/kg did not prolong the bleeding time.
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Interaction with warfarin (rats)
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NKCP at 250mg/kg was administered into the duodenum by the in situ loop method in rats, in which bleeding time was delayed by treatment with warfarin, and blood collected after 6 hours was measured for coagulation time. The warfarin treatment significantly prolonged the coagulation time in comparison with the control group, but no added delay of coagulation was observed in the warfarin+NKCP treatment group compared with warfarin treatment group.
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Long-term administration in humans
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Twenty-three healthy adults were given NKCP at 250mg/day for 12 weeks, and no clinically significant adverse events were observed. There were no statistically significant changes in hematological or biochemistry tests.
Five healthy adults were given NKCP at 750mg/day for 6 consecutive weeks to study and observe changes in laboratory test values (hematological tests, biochemistry tests, and blood coagulation/fibrinolysis parameters) and adverse events. As a result, ELT shortened, t-PA decreased, and thromboplastinogen activity test (TAT) increased but all values were within normal range. In addition, no adverse events were observed, suggesting NKCP safety.
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High dose administration in humans
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Eight healthy adults were given NKCP at 1,250mg/day for 7 consecutive days. Observation of clinical signs and laboratory tests were utilized to evaluate NKCP safety. There were no clinically significant adverse events. There were no abnormal changes in hematological or biochemistry tests.
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