Freeze-dried B type natriuretic peptide preparation and preparation method thereof
A technology for natriuretic peptides and preparations, applied in the field of biopharmaceuticals, can solve the problems of inability to form crystal nuclei, difficult to guarantee product safety, and inability to guarantee the freeze-drying effect of B-type natriuretic peptides.
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[0073] Preparation method of freeze-dried B-type natriuretic peptide preparation
[0074] The invention provides a method for preparing a freeze-dried B-type natriuretic peptide preparation, the method comprising the steps of:
[0075] (a) providing an isotonic solution containing B-type natriuretic peptide;
[0076] (b) The temperature of the isotonic solution containing B-type natriuretic peptide is reduced to the pre-freezing temperature interval T 0 , and keep it for a period of time P0, thereby forming a pre-frozen frozen mixture, wherein, the T 0 -70°C to -40°C, preferably -50°C to -45°C, P0 is 0.5 to 48 hours;
[0077] (c) raising the temperature of the pre-frozen frozen mixture to the first sublimation temperature interval Ts 1 , and maintain for a period of time P1 for the first sublimation, where Ts 1 -45°C to -20°C, preferably -45°C to -40°C;
[0078] (d) heating the frozen mixture obtained in step (c) to the second sublimation temperature interval Ts 2 , and ...
Embodiment 1
[0142] Example 1 Preparation of lyophilized B-type natriuretic peptide preparation
[0143] (1) Preparation of solution
[0144] ① Add a certain amount of disodium hydrogen phosphate, sodium dihydrogen phosphate, and sodium chloride to the B-type natriuretic peptide in the original solution after separation and purification.
[0145] ②Use a 0.22um filter to filter and sterilize the stock solution of B-type natriuretic peptide.
[0146] ③Under a sterile environment, add a certain amount of mannitol (the final prepared solution contains 8mg / ml), add a small amount of water for injection to dissolve, and shake well.
[0147] (2) Dissolving filling
[0148] ① Add an appropriate amount of water for injection to dissolve, and constant volume, stir well, and then filter the sample with a 0.22um filter. Use a filling machine to subpackage into 1ml sample solution each.
[0149] (3) Freeze-dried preparation
[0150] ①Clean and sterilize the freeze-drying tray in the freeze-drying ...
Embodiment 2-24
[0152] Example 2-24 Preparation of lyophilized B-type natriuretic peptide preparation
[0153] The preparation of freeze-dried B-type natriuretic peptide preparation was carried out according to the method similar to that of Example 1, wherein different experimental conditions are shown in Table 1.
[0154] Table 1 Comparison of different experimental conditions in each embodiment of the present invention
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[0157] Table 2 Comparison table of physical and chemical properties of B-type natriuretic peptide preparations prepared in each example
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PUM
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