Drug category Human brain natriuretic peptide is B-type natriuretic peptide, an endogenous peptide secreted by the human body. It is a supplementary peptide produced in large quantities by the human body after stress induced heart failure. compensation mechanism. This product is a sterile freeze-dried preparation produced by E. coli through recombinant DNA technology. It has the same amino acid sequence as the endogenous brain natriuretic peptide produced by ventricular muscle. Mechanism of action Human brain natriuretic peptide binds to a specific natriuretic peptide receptor (which is coupled to guanylyl cyclase), causing an increase in the concentration of intracellular cyclic guanosine monophosphate (cGMP). and relaxation of smooth muscle cells. As a second messenger, cGMP can dilate arteries and veins, rapidly reduce systemic arterial pressure, right atrial pressure, and pulmonary capillary wedge pressure, thereby reducing the preload and postload of the heart and rapidly reducing dyspnea and systemic symptoms in patients with heart failure. Brain natriuretic peptide is a natural antagonist of the renin-angiotensin-aldosterone system (RAAS), which antagonizes endothelin, norepinephrine, and aldosterone in cardiomyocytes, cardiac fibroblasts, and vascular smooth muscle cells. It can increase the glomerular filtration rate, enhance sodium excretion, reduce the secretion of renin and aldosterone, and resist the sodium and water retention and blood pressure-raising effects of vasopressin and sympathetic nerves. Brain natriuretic peptide participates in the regulation of blood pressure, blood volume, and water-salt balance, increases vascular permeability, reduces systemic vascular resistance and plasma volume, thereby reducing cardiac preload and afterload, and increasing cardiac output. This product has no positive inotropic effect and does not increase myocardial oxygen consumption. The entire clinical pharmacology trial was conducted in 12 cardiovascular clinical research bases across the country. A total of 209 subjects were randomly enrolled and received drug treatment (105 cases in the product group and 104 cases in the control group), including the catheter group 103 cases (51 cases in this product group and 52 cases in the control group), and 106 cases in the non-catheter group (54 cases in this product group and 52 cases in the control group). In terms of efficacy analysis, hemodynamic index evaluation, pulmonary capillary wedge pressure (PCWP) comparison before and after treatment, and (ITT) population analysis, both the product group and the control group showed a downward trend after treatment. At the end of 24 hours of medication, the pulmonary capillary wedge pressure (PCWP) of this product group dropped by an average of 9.13mmHg, while that of the control group dropped by an average of 4.56mmHg at the end of 24 hours of medication. Comparing the change values ??between the two groups, There is a significant difference (P=0.0368). In the analysis of the population in compliance with the protocol (PP population), there was a significant difference in the change values ??between the two groups (P=0.0368). The adjusted average value of pulmonary artery pressure (PAP) detection value in this product group was significantly different from that in the control group at 30 minutes, 1 hour, 2 hours and 24 hours after medication (P0.05). The mean changes in CI detection values ??in the recombinant human brain natriuretic peptide group increased by 0.05L/min/m2 at 1 hour and 24 hours after treatment, and by 0.11L/min/m2 and 0.10 L/min/m2 in the control group, respectively. There was no significant difference in the statistical comparison of the mean change values ??of CI detection between the test group and the control group at 1 hour and 24 hours after drug administration. The mean changes in RAP detection values ??in the drug group decreased by 2.55mmHg and 4.83mmHg respectively at 1 hour and 24 hours after administration, while in the control group, they increased by 2.57mmHg at 1 hour and decreased by 1.19mmHg at 24 hours. However, there was no significant difference in the statistical comparison of the RAP-adjusted mean values ??between the 1 hour of medication and 24 hours of medication between the Benzoate group and the control group. Hemodynamic results showed that during the 24-hour medication period, the improvement in hemodynamic function was significantly better than that of nitroglycerin. Comparison of the improvement rate of dyspnea and systemic clinical conditions at the end of 24 hours of medication between the two groups, analysis of ITT population and PP population, the improvement rate of dyspnea and systemic clinical conditions in the product group was significantly higher than that of the control group (P Non-clinical toxicology study Monkey acute toxicity test: This test observes the acute toxicity of this product to monkeys after intravenous infusion at a dose of 0.720 mg/kg-3.645 mg/kg. No other acute toxic reactions were observed for 14 days. Monkey long-term toxicity test: Observe the long-term toxicity of continuous intravenous infusion of this product to rhesus monkeys for 30 days. Method: 24 healthy male and female rhesus monkeys were randomly divided into 4 groups according to body weight: blank control group, low-dose group, medium-dose group, and high-dose group. There were 6 animals in each group, half male and half male. The dosages in the low, medium and high dose groups were 0.03, 0.09 and 0.3 mg/kg respectively.

Inject the drug into 50 ml of the solvent provided by the development unit for intravenous infusion every morning before feeding for 30 consecutive days. The blank control group is intravenously infused with an equal amount of the solvent provided by the development unit. One day after the last dose, half of the animals were sacrificed for pathological anatomy, and the other half were observed for 15 days after drug withdrawal. Observe symptoms and various test indicators. The test results show that the main effects of this product on the cardiovascular and urinary systems of monkeys are blood pressure lowering and diuresis. The target organs of this product's pharmacological toxic effects on monkeys are: liver and kidney, and its effects are reversible. During clinical use, close attention should be paid to the effects of this product on blood pressure, liver and kidney functions. Carcinogenicity and genotoxicity test: At present, no specific research has been conducted at home or abroad on the carcinogenicity and genotoxicity of recombinant human brain natriuretic peptide.