BC10131 New Drug Project
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New drug name: edible and medicinal mushroom polysaccharide natural hypolipidemic active ingredient
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Registration classification: Class 1.2 of traditional Chinese medicine
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Current research stage: preclinical
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Indications: Type II diabetes
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Intellectual property rights: US patents
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The characteristics of this achievement: multi-target, various administration methods are effective and safe polysaccharide with blood sugar regulation function
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Introduction to the results of the study
7.1 Study on the hypoglycemic effect of BC10131
BC10131 (50 mg/kg BW) can reduce fasting blood glucose and improve insulin resistance in T2DM rats; BC10131 can increase the expression of IR and IRS1, but does not activate the PI3K-Akt pathway. BC10131 ultimately lowers blood glucose by inhibiting the expression of protein tyrosine phosphatase 1B (PTP1B).
7.2 Pharmacodynamic study:
(1) The efficacy of BC10131 is slightly better than that of metformin.
(2) The effect of BC10131 on blood lipids: After 6 weeks of high-fat and high-sugar diet feeding, TC and TG of mice in DC group were significantly increased (P < 0.0001), showing lipid metabolism disorder. Four items of blood lipids (TC, TG, LDL-C) were improved in BC10131-treated mice (P < 0.0001; P < 0.01; P < 0.05).
(3) BC10131 can effectively improve insulin resistance: HOMA-IR (P < 0.01) increased in DC group. BC10131 could effectively improve insulin resistance (P < 0.05; P < 0.05; P < 0.0001).
7.3 Safety evaluation: various indicators of serum of mice injected with BC10131 for 14d and 90d
Kunming mice (half male and half male) were given BC10131 (2000 mg/kg/d) for 14 consecutive days. During the experimental observation period, BC10131 had no effect on the body weight of the mice. The animals in each group had normal diet and activity, and grew well without any symptoms. Poisoning performance, no death. After continuous intragastric administration of BC10131 (2000 mg/kg/d) for 14 days, there was no obvious toxic increase in the expression levels of its serum indexes.
Kunming mice (half male and half) were given BC10131 (500, 1000 mg/kg/d) for 90 consecutive days. During the observation period, BC10131 had no effect on the body weight of the mice. The animals in each group had normal diet and activity, and grew well. There were no signs of poisoning, and no death. After continuous gavage of BC10131 (500, 1000 mg/kg/d) for 90 days, except for urea UREA, which increased significantly (** P < 0.01), the expression levels of various indicators in serum showed no obvious toxicology. Sex increases.
Therefore, according to the toxicity test of repeated intragastric administration of mice for 14 days and 90 days, it can be seen that the LD50 of BC10131 is > 2000 mg/kg, which is much higher than the recommended dose (1 mg/kg) of the test population by 100 times. BC10131 is non-toxic.
7.4 Hypoglycemic mechanism
BC10131 may promote the excretion of bile acids in the body by promoting the conversion of conjugated bile acids to free bile acids in DM mice, and achieve the effect of improving glucose and lipid metabolism disorders (lowering blood sugar, blood lipids, and improving insulin resistance).
By determining the bacterial 16s rDNA V3-4 interval sequence of the intestinal contents of rats treated with BC10131, and conducting bioinformatics analysis, it was found that BC10131 can improve the composition of intestinal flora and regulate the metabolic function of the flora. At the same time, by measuring the expression of inflammatory factors and key factors in the Toll-like receptor 4/MyD88/NF-κB pathway in T2DM epididymal adipose tissue, it was found that BC10131 can inhibit the level of inflammation in target organs.
7.5 Nonclinical Pharmacokinetic Studies
Plasma concentration-time curve:
Tmax (time to peak) is about 6 h. It shows that the absorption of BC10131-FITC in rats is slow and the peak is delayed.
Panel A, Cumulative amounts of BC10131-FITC in urine at different time periods after intragastric administration of 50, 100, and 200 mg/kg:
Panel B, the cumulative amount of BC10131-FITC in feces at different time periods after oral administration of 50, 100, and 200 mg/kg doses:
Figure A, 48h after administration, the cumulative excretion of BC10131-FITC in the urine of each dose group accounted for 0.76%, 0.60%, and 0.63% of the dose, respectively;
Figure B, after 24 hours of administration, it was rapidly excreted in the feces (Figure B), reaching 72.91%, 78.46%, and 80.30%, respectively. The response value was almost undetectable within 24-48 hours, indicating that after the drug was absorbed, it was mainly within 24 hours. Excreted through feces.
Contact information
elisa@bestbiochem.com
