Drying method for biological medicine pharmaceutical processing

Abstract

The invention provides a drying method for biological medicine pharmaceutical processing, and relates to the technical field of biological pharmacy. The drying method for biological medicine pharmaceutical processing comprises the following steps: step 1, mixing and dissolving: mixing a protein medicine with absolute ethyl alcohol, ethylene glycol, glycerol and glycine, so that the protein medicine is dissolved in the absolute ethyl alcohol; step 2, decompression separation: adjusting the vacuum degree of the solution environment by gradually reducing the air pressure, and further separating absolute ethyl alcohol, ethylene glycol and glycerol in sequence; step 3, filtering: adjusting the vacuum degree of the solution environment to atmospheric pressure, and filtering out the separated protein, so that the protein drug is separated from glycine; and 4, collecting the dried protein drug powder. After being treated by a drying method, the protein medicine powder keeps good biological activity, is uniformly dried and has no agglomeration phenomenon. Meanwhile, compared with an untreated medicine, the storage stability of the medicine is remarkably improved.

Description

Technical Field

[0001] The invention relates to the technical field of biopharmaceuticals, in particular to a drying method for biopharmaceutical processing. Background Art

[0002] Biopharmaceuticals refer to drugs that are manufactured from organisms, biological tissues, cells, body fluids, etc., using the research results of microbiology, biology, medicine, biochemistry, etc., and using the scientific principles and methods of microbiology, chemistry, biochemistry, biotechnology, pharmacy, etc. Biopharmaceuticals include vaccines, diagnostic reagents, monoclonal antibodies, recombinant proteins, and blood products.

[0003] Protein drugs in biopharmaceuticals often need to be dried during processing to maintain their stability and extend their shelf life. Traditional drying methods such as hot air drying or spray drying may cause denaturation or degradation of active ingredients, affecting product quality and efficacy. Summary of the invention

[0004] 1. Technical issues to be solved

[0005] In view of the deficiencies of the prior art, the present invention provides a drying method for biopharmaceutical pharmaceutical processing, which solves the problem that the drying method in the traditional biopharmaceutical process will affect the activity of protein drugs.

[0006] (II) Technical solution

[0007] To achieve the above objectives, the present invention is implemented through the following technical solutions: A drying method for biopharmaceutical pharmaceutical processing, comprising the following steps:

[0008] Step 1: Mixing and dissolving: mixing the protein drug with anhydrous ethanol, ethylene glycol, glycerol and glycine, so that the protein drug is dissolved in the anhydrous ethanol;

[0009] Step 2: separation by reducing pressure, by gradually reducing the air pressure and adjusting the vacuum degree of the solution environment, thereby separating anhydrous ethanol, ethylene glycol and glycerin in turn;

[0010] Step 3: Filtration: adjusting the vacuum degree of the solution environment to atmospheric pressure, and filtering out the precipitated protein to separate the protein drug from glycine;

[0011] Step 4: Collect the dried protein drug powder and conduct quality inspection and biological activity evaluation.

[0012] Preferably, the mass ratio of the protein drug to anhydrous ethanol, ethylene glycol, glycerol and glycine is 10:(80-100):(10-20):(1-5):(0-1).

[0013] Preferably, the separation gas pressure of the anhydrous ethanol is set to (4-5) kPa, and the separation time is 2-4 h.

[0014] Preferably, the separation pressure of the ethylene glycol is set to (1-2) kPa, and the separation time is 1-3 h.

[0015] Preferably, the separation pressure of the glycerol is set to (0.3-0.5) kPa, and the separation time is 1-2 h.

[0016] Preferably, the heating temperature for the reduced pressure separation is set to 20-40°C.

[0017] Preferably, a semipermeable membrane is used for filtration during the filtration process.

[0018] Preferably, the quality inspection and biological activity assessment items in step 4 include but are not limited to biochemical analysis, physicochemical analysis, biophysical analysis, protein quantitative analysis, Fab / Fc functional detection, cell function experiment and immune response assessment.

[0019] (III) Beneficial effects

[0020] The present invention provides a drying method for biopharmaceutical pharmaceutical processing. It has the following beneficial effects:

[0021] 1. After being treated by the drying method of the present invention, the biological activity of the protein drug powder is maintained well, and the powder is dried evenly without agglomeration. At the same time, compared with the untreated drug, its storage stability is significantly improved.

[0022] 2. This drying method can effectively dissolve the protein through the combination of anhydrous ethanol, ethylene glycol, glycerol and glycine, thereby facilitating the absorption of water in the protein and effectively improving the drying effect of the protein drug. DETAILED DESCRIPTION

[0023] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0024] Embodiment 1:

[0025] The embodiment of the present invention provides a drying method for biopharmaceutical pharmaceutical processing, comprising the steps of: first, mixing and dissolving, mixing a protein drug with anhydrous ethanol, ethylene glycol, glycerol and glycine, so that the protein drug is dissolved in the anhydrous ethanol, and the mass ratio of the protein drug to the anhydrous ethanol, ethylene glycol, glycerol and glycine is 10:80:10:1:0.2;

[0026] Step 2, separation under reduced pressure, by gradually reducing the air pressure, adjusting the vacuum degree of the solution environment, and then separating anhydrous ethanol, ethylene glycol and glycerol in turn, the separation air pressure of anhydrous ethanol is set to 4 kPa, the separation time is 4 h, the separation air pressure of ethylene glycol is set to 1 kPa, the separation time is 3 h, the separation air pressure of glycerol is set to 0.5) kPa, the separation time is 2 h, and the heating temperature of the reduced pressure separation is set to 39 ° C.

[0027] Step 3: Filtration: adjusting the vacuum degree of the solution environment to atmospheric pressure, and filtering the precipitated protein through a semipermeable membrane to separate the protein drug from glycine;

[0028] Step 4: Collect the dried protein drug powder and conduct quality inspection and bioactivity evaluation. The quality inspection and bioactivity evaluation items include but are not limited to biochemical analysis, physicochemical analysis, biophysical analysis, protein quantitative analysis, Fab / Fc functional detection, cell function experiment and immune response evaluation.

[0029] Embodiment 2:

[0030] The embodiment of the present invention provides a drying method for biopharmaceutical pharmaceutical processing, comprising the steps of: step 1, mixing and dissolving, mixing a protein drug with anhydrous ethanol, ethylene glycol, glycerol and glycine, so that the protein drug is dissolved in the anhydrous ethanol, and the mass ratio of the protein drug to the anhydrous ethanol, ethylene glycol, glycerol and glycine is 10:100:15:2:1;

[0031] Step 2, separation under reduced pressure, by gradually reducing the air pressure, adjusting the vacuum degree of the solution environment, and then separating anhydrous ethanol, ethylene glycol and glycerol in turn, the separation air pressure of anhydrous ethanol is set to 5kPa, the separation time is 4h, the separation air pressure of ethylene glycol is set to 3kPa, the separation time is 4h, the separation air pressure of glycerol is set to 0.3kPa, the separation time is 2h, and the heating temperature of the reduced pressure separation is set to 30°C.

[0032] Step 3: Filtration: adjusting the vacuum degree of the solution environment to atmospheric pressure, and filtering the precipitated protein through a semipermeable membrane to separate the protein drug from glycine;

[0033] Step 4: Collect the dried protein drug powder and conduct quality inspection and bioactivity evaluation. The quality inspection and bioactivity evaluation items include but are not limited to biochemical analysis, physicochemical analysis, biophysical analysis, protein quantitative analysis, Fab / Fc functional detection, cell function experiment and immune response evaluation.

[0034] Embodiment three:

[0035] The embodiment of the present invention provides a drying method for biopharmaceutical pharmaceutical processing, comprising the steps of: first, mixing and dissolving, mixing a protein drug with anhydrous ethanol, ethylene glycol, glycerol and glycine, so that the protein drug is dissolved in the anhydrous ethanol, and the mass ratio of the protein drug to the anhydrous ethanol, ethylene glycol, glycerol and glycine is 10:90:15:5:0.5;

[0036] Step 2, separation under reduced pressure, by gradually reducing the air pressure, adjusting the vacuum degree of the solution environment, and then separating anhydrous ethanol, ethylene glycol and glycerol in turn, the separation air pressure of anhydrous ethanol is set to 4.5 kPa, the separation time is 4 hours, the separation air pressure of ethylene glycol is set to 3 kPa, the separation time is 3 hours, the separation air pressure of glycerol is set to 0.5 kPa, the separation time is 2 hours, and the heating temperature of the reduced pressure separation is set to 25 ° C.

[0037] Step 3: Filtration: adjusting the vacuum degree of the solution environment to atmospheric pressure, and filtering the precipitated protein through a semipermeable membrane to separate the protein drug from glycine;

[0038] Step 4: Collect the dried protein drug powder and conduct quality inspection and bioactivity evaluation. The quality inspection and bioactivity evaluation items include but are not limited to biochemical analysis, physicochemical analysis, biophysical analysis, protein quantitative analysis, Fab / Fc functional detection, cell function experiment and immune response evaluation.

[0039] Embodiment 4:

[0040] The embodiment of the present invention provides a drying method for biopharmaceutical pharmaceutical processing, comprising the steps of: step 1, mixing and dissolving, mixing a protein drug with anhydrous ethanol, ethylene glycol, glycerol and glycine, so that the protein drug is dissolved in the anhydrous ethanol, and the mass ratio of the protein drug to the anhydrous ethanol, ethylene glycol, glycerol and glycine is 10:80:10:1:0.25;

[0041] Step 2, separation under reduced pressure, by gradually reducing the air pressure, adjusting the vacuum degree of the solution environment, and then separating anhydrous ethanol, ethylene glycol and glycerol in turn, the separation air pressure of anhydrous ethanol is set to 5kPa, the separation time is 2h, the separation air pressure of ethylene glycol is set to 2kPa, the separation time is 2h, the separation air pressure of glycerol is set to 0.4kPa, the separation time is 2h, and the heating temperature of the reduced pressure separation is set to 35°C.

[0042] Step 3: Filtration: adjusting the vacuum degree of the solution environment to atmospheric pressure, and filtering the precipitated protein through a semipermeable membrane to separate the protein drug from glycine;

[0043] Step 4: Collect the dried protein drug powder and conduct quality inspection and bioactivity evaluation. The quality inspection and bioactivity evaluation items include but are not limited to biochemical analysis, physicochemical analysis, biophysical analysis, protein quantitative analysis, Fab / Fc functional detection, cell function experiment and immune response evaluation.

[0044] Embodiment five:

[0045] The embodiment of the present invention provides a drying method for biopharmaceutical pharmaceutical processing, comprising the steps of: first, mixing and dissolving, mixing a protein drug with anhydrous ethanol, ethylene glycol, glycerol and glycine, so that the protein drug is dissolved in the anhydrous ethanol, and the mass ratio of the protein drug to the anhydrous ethanol, ethylene glycol, glycerol and glycine is 10:95:15:4:0.3;

[0046] Step 2, separation under reduced pressure, by gradually reducing the air pressure, adjusting the vacuum degree of the solution environment, and then separating anhydrous ethanol, ethylene glycol and glycerol in turn, the separation air pressure of anhydrous ethanol is set to 4 kPa, the separation time is 3 h, the separation air pressure of ethylene glycol is set to 1.5 kPa, the separation time is 1 h, the separation air pressure of glycerol is set to 0.3 kPa, the separation time is 1 h, and the heating temperature of the reduced pressure separation is set to 30 ° C.

[0047] Step 3: Filtration: adjusting the vacuum degree of the solution environment to atmospheric pressure, and filtering the precipitated protein through a semipermeable membrane to separate the protein drug from glycine;

[0048] Step 4: Collect the dried protein drug powder and conduct quality inspection and bioactivity evaluation. The quality inspection and bioactivity evaluation items include but are not limited to biochemical analysis, physicochemical analysis, biophysical analysis, protein quantitative analysis, Fab / Fc functional detection, cell function experiment and immune response evaluation.

[0049] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A drying method for biopharmaceutical pharmaceutical processing, characterized in that: The following steps are involved: Step 1: Mixing and dissolving: mixing the protein drug with anhydrous ethanol, ethylene glycol, glycerol and glycine, so that the protein drug is dissolved in the anhydrous ethanol; Step 2: separation by reducing pressure, by gradually reducing the gas pressure and adjusting the vacuum degree of the solution environment, thereby separating anhydrous ethanol, ethylene glycol and glycerin in turn; Step 3: Filtration: adjusting the vacuum degree of the solution environment to atmospheric pressure, and filtering out the precipitated protein to separate the protein drug from glycine; Step 4: Collect the dried protein drug powder and conduct quality inspection and biological activity evaluation.

2. A drying method for biopharmaceutical pharmaceutical processing according to claim 1, characterized in that: The mass ratio of the protein drug to anhydrous ethanol, ethylene glycol, glycerol and glycine is 10:(80-100):(10-20):(1-5):(0-1).

3. A drying method for biopharmaceutical pharmaceutical processing according to claim 1, characterized in that: The separation gas pressure of the anhydrous ethanol is set to (4-5) kPa, and the separation time is 2-4 hours.

4. A drying method for biopharmaceutical pharmaceutical processing according to claim 1, characterized in that: The separation gas pressure of the ethylene glycol is set to (1-2) kPa, and the separation time is 1-3 hours.

5. A drying method for biopharmaceutical pharmaceutical processing according to claim 1, characterized in that: The separation pressure of the glycerol is set to (0.3-0.5) kPa, and the separation time is 1-2h.

6. A drying method for biopharmaceutical pharmaceutical processing according to claim 1, characterized in that: The heating temperature of the reduced pressure separation is set to 20-40°C.

7. A drying method for biopharmaceutical pharmaceutical processing according to claim 1, characterized in that: A semipermeable membrane is used for filtration during the filtration process.

8. A drying method for biopharmaceutical pharmaceutical processing according to claim 1, characterized in that: The quality inspection and biological activity evaluation items in step 4 include, but are not limited to, biochemical analysis, physicochemical analysis, biophysical analysis, protein quantitative analysis, Fab / Fc functional testing, cell function experiments, and immune response evaluation.