CN114272372A - Monoclonal antibody freeze-dried powder preparation and preparation process thereof - Google Patents
Monoclonal antibody freeze-dried powder preparation and preparation process thereof Download PDFInfo
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- CN114272372A CN114272372A CN202111626495.5A CN202111626495A CN114272372A CN 114272372 A CN114272372 A CN 114272372A CN 202111626495 A CN202111626495 A CN 202111626495A CN 114272372 A CN114272372 A CN 114272372A
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Abstract
The invention provides a monoclonal antibody freeze-dried powder preparation and a preparation process thereof, and relates to the technical field of protein and polypeptide medicines. The freeze-dried powder preparation based on the monoclonal antibody comprises the antibody, a protective agent, an excipient and a quick freezing agent. Through carrying out cubic circulation sublimation drying to freeze-dried sample, can guarantee that sublimation drying's vapor and moisture is taken away every time, can prevent that the sample from taking place the phenomenon of conditioning, also guarantee the moisture in the sample simultaneously and expect, can reduce the water content of freeze-dried powder, add quick-freezing agent in the freeze-dried powder preparation, carry out frozen in-process to freeze-dried sample, can accelerate the freezing speed of freeze-dried powder, reduce the freeze-drying time, improve frozen speed, reduce the preparation time of freeze-dried powder preparation simultaneously.
Description
Technical Field
The invention relates to the technical field of protein and polypeptide medicines, in particular to a monoclonal antibody freeze-dried powder preparation and a preparation process thereof.
Background
Monoclonal antibodies are highly homogeneous antibodies produced by a single B cell clone that are directed against only a particular epitope. Usually, hybridoma (hybridoma) antibody technology is used to prepare a specific antibody against an epitope, i.e., a monoclonal antibody, by fusing a sensitized B cell having the ability to secrete a specific antibody and a myeloma cell having the ability to reproduce indefinitely into a B cell hybridoma based on cell fusion technology, and culturing the individual hybridoma cells having such characteristics into a cell population.
The preparation time of the freeze-dried powder preparation in the existing preparation process of some monoclonal antibody freeze-dried powder preparations is longer, and meanwhile, the water content in some freeze-dried powder is more, so that the practicability of the freeze-dried powder preparation is reduced.
Disclosure of Invention
Technical problem to be solved
Aiming at the defects of the prior art, the invention provides a monoclonal antibody freeze-dried powder preparation and a preparation process thereof, and solves the problems of more water content and longer preparation time of the freeze-dried preparation.
(II) technical scheme
In order to achieve the purpose, the invention is realized by the following technical scheme: a freeze-dried powder of monoclonal antibody is prepared from antibody, protecting agent, excipient and quick-freezing agent.
Preferably, the protective agent is one of trehalose, dextran and dextrin.
Preferably, the excipient is one of maltose, liposome and protein.
Preferably, the quick-freezing agent is one of solid carbon dioxide and high-grade environment-friendly refrigerant.
Preferably, the dose of the protective agent is 10-35 mM.
Preferably, the dosage of the quick freezing agent is 10-30 mM.
Preferably, the dose of the antibody is 110-125 mg/ml.
Preferably, the excipient dose is 10-150 mg/ml.
Preferably, the preparation process of the monoclonal antibody lyophilized powder preparation according to the above description comprises the following steps:
s1: sample preparation: the sample formulation described above forms a lyophilized sample by adding a buffer;
s2, pre-freezing: placing the freeze-dried sample in a freeze dryer, pre-freezing for 0.4H at the set temperature of-2 ℃, and cooling to-50 ℃ for 1.5-2.0H;
s3, circulating sublimation and drying:
(1) carrying out first sublimation drying; pumping out gas in the freeze dryer to make the freeze dryer in a vacuum state, and then heating the temperature in the freeze dryer to-30 to-20 ℃ to maintain the temperature at 10-20H;
(2) and carrying out sublimation drying for the second time: raising the temperature in the freeze-drying machine to-20 to-10 ℃ and maintaining the temperature for 10-20H;
(3) and carrying out sublimation drying for the third time: the temperature in the freeze-dryer was raised to 0-10 deg.C and maintained at 10-20 deg.C.
(III) advantageous effects
The invention provides a monoclonal antibody freeze-dried powder preparation and a preparation process thereof. The method has the following beneficial effects:
1. according to the invention, when the freeze-dried sample is subjected to three times of circulating sublimation drying, the vapor and the moisture of each time of sublimation drying can be ensured to be pumped away, the sample can be prevented from being remoistened, the moisture in the sample can be ensured to be discharged, and the moisture content of the freeze-dried powder can be reduced.
2. According to the invention, the quick-freezing agent is added into the freeze-dried powder preparation, so that the freezing speed of the freeze-dried powder can be increased, the freezing time can be shortened, the freezing speed can be increased, and the preparation time of the freeze-dried powder preparation can be shortened.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The first embodiment is as follows:
the embodiment of the invention provides a monoclonal antibody freeze-dried powder preparation which comprises an antibody, a protective agent, an excipient and a quick freezing agent, wherein the dosage of the antibody is 110mg/ml, the protective agent is trehalose, the dosage of the protective agent is 10mM, the excipient is maltose, the dosage of the excipient is 10mg/ml, the quick freezing agent is solid carbon dioxide, and the dosage of the quick freezing agent is 10 mM.
The preparation process of the monoclonal antibody lyophilized powder preparation comprises the following steps:
s1: sample preparation: forming a lyophilized sample by adding a buffer solution according to the sample formula 1-8;
s2, pre-freezing: placing the freeze-dried sample in a freeze dryer, pre-freezing for 0.4H at the set temperature of-2 ℃, and cooling to-50 ℃ for maintaining for 2.0H;
s3, circulating sublimation and drying:
(1) carrying out first sublimation drying; pumping away the gas in the freeze dryer to make the freeze dryer in a vacuum state, and then raising the temperature in the freeze dryer to-30 ℃ to maintain the temperature for 10H;
(2) and carrying out sublimation drying for the second time: heating the temperature in the freeze-drying machine to-20 deg.C, and maintaining the temperature for 10-20H;
(3) and carrying out sublimation drying for the third time: the temperature in the freeze-dryer was raised to 0 ℃ and maintained at 10-20H.
Example two:
the embodiment of the invention provides a monoclonal antibody freeze-dried powder preparation which comprises an antibody, a protective agent, an excipient and a quick freezing agent, wherein the dosage of the antibody is 120mg/ml, the protective agent is glucan, the dosage of the protective agent is 25mM, the excipient is a liposome, the dosage of the excipient is 80mg/ml, the quick freezing agent is a high-grade environment-friendly refrigerant, and the dosage of the quick freezing agent is 20 mM.
The preparation process of the monoclonal antibody lyophilized powder preparation comprises the following steps:
s1: sample preparation: forming a lyophilized sample by adding a buffer solution according to the sample formula 1-8;
s2, pre-freezing: placing the freeze-dried sample in a freeze dryer, pre-freezing for 0.4H at the set temperature of-2 ℃, and cooling to-50 ℃ for 1.8H;
s3, circulating sublimation and drying:
(1) carrying out first sublimation drying; pumping away the gas in the freeze dryer to make the freeze dryer in a vacuum state, and then raising the temperature in the freeze dryer to-25 ℃ to maintain the temperature for 15H;
(2) and carrying out sublimation drying for the second time: raising the temperature in the freeze-dryer to-25 ℃ and maintaining the temperature for 15H;
(3) and carrying out sublimation drying for the third time: the temperature in the freeze-dryer was raised to 5 ℃ and maintained at 15H.
Example three:
the embodiment of the invention provides a monoclonal antibody freeze-dried powder preparation which comprises an antibody, a protective agent, an excipient and a quick freezing agent, wherein the dosage of the antibody is 125mg/ml, the protective agent is dextrin, the dosage of the protective agent is 30mM, the excipient is protein, the dosage of the excipient is 150mg/ml, the quick freezing agent is solid carbon dioxide, and the dosage of the quick freezing agent is 30 mM.
The preparation process of the monoclonal antibody lyophilized powder preparation comprises the following steps:
s1: sample preparation: forming a lyophilized sample by adding a buffer solution according to the sample formula 1-8;
s2, pre-freezing: placing the freeze-dried sample in a freeze dryer, pre-freezing for 0.4H at the set temperature of-2 ℃, and cooling to-50 ℃ for 1H;
s3, circulating sublimation and drying:
(1) carrying out first sublimation drying; pumping away the gas in the freeze dryer to make the freeze dryer in a vacuum state, and then raising the temperature in the freeze dryer to-20 ℃ to maintain the temperature for 20H;
(2) and carrying out sublimation drying for the second time: raising the temperature in the freeze-dryer to-10 ℃ and maintaining the temperature for 20H;
(3) and carrying out sublimation drying for the third time: the temperature in the freeze-dryer was raised to 10 ℃ and maintained at 20H.
The production is carried out by the prior art:
| moisture content (%) | Freezing time (H) | |
| Example 1 | 2.5 | 2 |
| Example 2 | 1.8 | 1.8 |
| Example 3 | 1 | 1 |
| Comparative example | 3 | 2.5 |
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (9)
1. A freeze-dried powder of monoclonal antibody is prepared from antibody, protecting agent, excipient and quick-freezing agent.
2. The lyophilized powder preparation of monoclonal antibody according to claim 1, wherein: the protective agent is one of trehalose, dextran and dextrin.
3. The lyophilized powder preparation of monoclonal antibody according to claim 1, wherein: the excipient is one of maltose, liposome and protein.
4. The lyophilized powder preparation of monoclonal antibody according to claim 1, wherein: the quick-freezing agent is one of solid carbon dioxide and high-grade environment-friendly refrigerant.
5. The lyophilized powder preparation of monoclonal antibody according to claim 1, wherein: the dosage of the protective agent is 10-35 mM.
6. The lyophilized powder preparation of monoclonal antibody according to claim 1, wherein: the dosage of the quick freezing agent is 10-30 mM.
7. The lyophilized powder preparation of monoclonal antibody according to claim 1, wherein: the dose of the antibody is 110-125 mg/ml.
8. The lyophilized powder preparation of monoclonal antibody according to claim 1, wherein: the dosage of the excipient is 10-150 mg/ml.
9. The preparation process of the monoclonal antibody freeze-dried powder preparation is characterized by comprising the following steps: the method comprises the following steps:
s1: sample preparation: the lyophilized powder preparation of monoclonal antibody according to claim 1 to 8, which is prepared by adding a buffer solution to form a lyophilized sample;
s2, pre-freezing: placing the freeze-dried sample in a freeze dryer, pre-freezing for 0.4H at the set temperature of-2 ℃, and cooling to-50 ℃ for 1.5-2.0H;
s3, circulating sublimation and drying:
(1) carrying out first sublimation drying; pumping out gas in the freeze dryer to make the freeze dryer in a vacuum state, and then heating the temperature in the freeze dryer to-30 to-20 ℃ to maintain the temperature at 10-20H;
(2) and carrying out sublimation drying for the second time: raising the temperature in the freeze-drying machine to-20 to-10 ℃ and maintaining the temperature for 10-20H;
(3) and carrying out sublimation drying for the third time: the temperature in the freeze-dryer was raised to 0-10 deg.C and maintained at 10-20H.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN117825688A (en) * | 2024-01-19 | 2024-04-05 | 武汉鹰达生物科技有限公司 | Animal IgG antibody freeze-dried powder preparation and preparation process thereof |
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