CN112807418A - Cetrorelix preparation and preparation method thereof - Google Patents
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Abstract
The invention discloses a cetrorelix preparation and a preparation method thereof, relating to the technical field of biological medicine, wherein the preparation method comprises the following steps of freezing a mixed solution containing mannitol and cetrorelix acetate in a first stage to a third stage, wherein the conditions of the first stage are as follows: cooling to-20 to-40 ℃, and then preserving heat for 0.1 to 2 hours; the conditions in the second stage are: heating to-20 to-5 ℃, and keeping the temperature for 0.1 to 2 hours; the conditions for the third stage were: cooling to-20-40 ℃, and then preserving heat for 0.1-2 h. The method reduces the temperature to be near the glass transition temperature of the solution, keeps for a period of time, and reduces the temperature again to completely freeze the solution after the temperature is raised to a certain temperature, so that the stability of the cetrorelix preparation product can be ensured to the maximum extent. Meanwhile, after the freezing treatment, higher drying temperature can be selected for drying in the drying stage, so that the product quality is not influenced, the drying time is shortened, and the production cost is reduced.
Description
Technical Field
The invention relates to the technical field of biological medicines, and particularly relates to a cetrorelix preparation and a preparation method thereof.
Background
Cetrorelix is a gonadotropin releasing hormone (LHRH) antagonist developed by the company ASTA MEDICA Germany, can control the stimulation effect of ovaries, prevent premature follicle from being discharged early and help conception. The method is mainly used for preventing advanced ovulation of a patient subjected to controlled ovarian stimulation, and then carrying out egg collection and assisted reproductive technology treatment.
The prior patent CN94101378.2 discloses a preparation method of a cetrorelix lyophilized pharmaceutical composition, which discloses a preparation method that acetic acid is adopted to dissolve cetrorelix, water for injection is added for dilution, then mannitol is added to obtain mannitol and cetrorelix solution, the solution is filtered, subpackaged and freeze-dried. The preparation method mainly solves the problems of difficult filtration and content loss, and then practices prove that the prepared trorelix freeze-dried pharmaceutical composition has the technical problem of poor stability.
The storage condition of the existing cetrorelix acetate for injection sold in China is 25 ℃, and the effective period is two years. Since cetrorelix acetate for injection in the market has poor stability in long-term storage and accelerated tests and related substances are greatly increased, the American FDA requires that the storage temperature is 2-8 ℃.
How to improve the stability of cetrorelix acetate so that the cetrorelix acetate can be stored for a long time at room temperature is one of the technical problems to be solved urgently today.
In view of this, the invention is particularly proposed.
Disclosure of Invention
The invention aims to provide a cetrorelix preparation and a preparation method thereof.
The invention is realized by the following steps:
in a first aspect, the embodiments of the present invention provide a method for preparing a cetrorelix preparation, which includes freezing a mixed solution containing mannitol and cetrorelix acetate, and then drying the mixed solution, wherein the freezing includes a first stage, a second stage and a third stage;
the conditions of the first stage are as follows: cooling to-20 to-40 ℃, and then preserving heat for 0.1 to 2 hours;
the conditions of the second stage are: heating to-20 to-5 ℃, and keeping the temperature for 0.1 to 2 hours;
the conditions of the third stage are: cooling to-20-40 ℃, and then preserving heat for 0.1-2 h.
In a second aspect, embodiments of the present invention provide a cetrorelix formulation prepared by the method of preparing the cetrorelix formulation described in any of the preceding embodiments.
The invention has the following beneficial effects:
the embodiment of the invention provides a cetrorelix preparation and a preparation method thereof, wherein the preparation method comprises the steps of freezing and drying a mixed solution containing mannitol and cetrorelix acetate, wherein the freezing step comprises a first stage, a second stage and a third stage;
the conditions of the first stage are as follows: cooling to-20 to-40 ℃, and then preserving heat for 0.1 to 2 hours;
the conditions of the second stage are: heating to-20 to-5 ℃, and keeping the temperature for 0.1 to 2 hours;
the conditions of the third stage are: cooling to-20-40 ℃, and then preserving heat for 0.1-2 h.
According to the invention, researches show that the temperature is reduced to be near the glass transition temperature (-30 ℃) of the mixed solution, the mixed solution is kept for a period of time, the mixed solution is cooled again after being heated to a certain temperature until the mixed solution is completely frozen, so that the stability of the cetrorelix preparation product is ensured to the maximum extent, and meanwhile, higher drying temperature can be selected for drying in the drying stage, so that the product quality is not influenced, the drying time is shortened, and the production cost is reduced.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The features and properties of the present invention are described in further detail below with reference to examples.
The embodiment of the invention provides a preparation method of a cetrorelix preparation, which comprises the steps of freezing and drying a mixed solution containing mannitol and cetrorelix acetate, wherein the freezing step comprises a first stage, a second stage and a third stage;
the conditions of the first stage are as follows: cooling to-20 to-40 ℃, and then preserving heat for 0.1 to 2 hours;
the conditions of the second stage are: heating to-20 to-5 ℃, and keeping the temperature for 0.1 to 2 hours;
the conditions of the third stage are: cooling to-20-40 ℃, and then preserving heat for 0.1-2 h.
Herein, "cetrorelix" is a compound that has the ability to control ovarian stimulation, prevent premature follicular discharge, and aid conception.
The inventor finds that in the freezing process of the mixed solution containing mannitol and cetrorelix acetate, the temperature is reduced to be near the glass transition temperature (-30 ℃) of the solution for a period of time, then the temperature is raised to a certain temperature and then reduced to be completely frozen, and the stability of the cetrorelix preparation product can be further ensured. Meanwhile, the solution can be dried at a higher drying temperature (such as 25 ℃) in the drying stage, so that the product quality is not influenced, the drying time is shortened, and the production cost is reduced.
In some embodiments, the first stage may be cooled to any of-20 ℃, -22 ℃, -24 ℃, -26 ℃, -28 ℃, -30 ℃, -32 ℃, -34 ℃, -36 ℃, -38 ℃, and-40 ℃.
In some embodiments, the incubation time for the first stage may be selected from: 0.1h, 0.2h, 0.4h, 0.6h, 0.8h, 1.0h, 1.2h, 1.4h, 1.6h, 1.8h and 2.0 h.
In some embodiments, the cooling rate of the first stage may be selected from: 0.1 ℃/min, 0.2 ℃/min, 0.4 ℃/min, 0.6 ℃/min, 0.8 ℃/min, 1.0 ℃/min, 1.2 ℃/min, 1.4 ℃/min, 1.6 ℃/min, 1.8 ℃/min, 2.0 ℃/min, 2.2 ℃/min, 2.4 ℃/min, and 2.5 ℃/min.
Preferably, the conditions of the first stage are: cooling to-25 to-35 ℃ at a cooling rate of 0.1 to 2.5 ℃/min, and then preserving heat for 0.5 to 1 hour. Under the optimal conditions, the prepared product has better stability.
More preferably, the temperature reduction rate of the first stage is 0.5-1.5 ℃/min.
In some embodiments, the second stage may be warmed to any of-20 ℃, -18 ℃, -16 ℃, -14 ℃, -12 ℃, -10 ℃, -8 ℃, -6 ℃ and-5 ℃.
In some embodiments, the incubation time for the second stage may be selected from: 0.1h, 0.2h, 0.4h, 0.6h, 0.8h, 1.0h, 1.2h, 1.4h, 1.6h, 1.8h and 2.0 h.
In some embodiments, the ramp rate of the second stage may be selected from: 0.1 ℃/min, 0.2 ℃/min, 0.4 ℃/min, 0.6 ℃/min, 0.8 ℃/min, 1.0 ℃/min, 1.2 ℃/min, 1.4 ℃/min, 1.6 ℃/min, 1.8 ℃/min, 2.0 ℃/min, 2.2 ℃/min, 2.4 ℃/min, and 2.5 ℃/min.
Preferably, the conditions of the second stage are: heating to-20 to-5 ℃ at a heating rate of 0.1 to 5 ℃/min, and keeping the temperature for 0.1 to 2 hours.
More preferably, the temperature rise rate of the second stage is 0.5-1.5 ℃/min.
In some embodiments, the third stage may cool to any of-20 ℃, -22 ℃, -24 ℃, -26 ℃, -28 ℃, -30 ℃, -32 ℃, -34 ℃, -36 ℃, -38 ℃, and-40 ℃.
In some embodiments, the incubation time for the third stage may be selected from: 0.1h, 0.2h, 0.4h, 0.6h, 0.8h, 1.0h, 1.2h, 1.4h, 1.6h, 1.8h and 2.0 h.
In some embodiments, the cooling rate for the third stage may be selected from: 0.1 ℃/min, 0.2 ℃/min, 0.4 ℃/min, 0.6 ℃/min, 0.8 ℃/min, 1.0 ℃/min, 1.2 ℃/min, 1.4 ℃/min, 1.6 ℃/min, 1.8 ℃/min, 2.0 ℃/min, 2.2 ℃/min, 2.4 ℃/min, and 2.5 ℃/min.
Preferably, the conditions of the third stage are: cooling to-20 to-40 ℃ at a cooling rate of 0.1 to 5 ℃/min, and then preserving heat for 0.1 to 2 hours.
More preferably, the temperature rise rate in the second stage is 0.1 to 1 ℃/min.
In some embodiments, the preparation method further comprises filtering the mixed solution containing mannitol and cetrorelix acetate before freeze-drying.
The preparation method of the mixed solution containing mannitol and cetrorelix acetate is not particularly limited, and the mixed solution can be obtained by the existing preparation method. Such as the dissolution of cetrorelix with glacial acetic acid or acetic acid.
Preferably, the filter used for filtering is a 0.1-1.0 μm filter. In some embodiments, the filter may have a size selected from any one of 0.1 μm, 0.2 μm, 0.4 μm, 0.6 μm, 0.8 μm, and 1 μm.
Preferably, the drying temperature is 5-25 ℃. In the prior art, after the freezing process, the frozen product is usually dried at a drying temperature of 5-20 ℃. The preparation product prepared by the method provided by the embodiment of the invention has high stability, can be dried at the drying temperature of 25 ℃, and effectively shortens the preparation time of the product and improves the production efficiency on the premise of not influencing the product quality.
In addition, the invention also provides a cetrorelix preparation prepared by the preparation method of the cetrorelix preparation according to any one of the embodiments.
The cetrorelix preparation provided by the invention has good stability and easy storage, can be stored in a room-temperature environment for a long time on the basis of keeping curative effect, and can remarkably improve the safety of clinical use of the cetrorelix preparation.
Example 1
The invention provides a preparation method of a cetrorelix preparation, which comprises the following steps:
(1) preparing a mixed solution containing mannitol and cetrorelix acetate:
TABLE 1 raw material ratio
Obtaining raw materials according to the components and the mixture ratio shown in the table 1;
adding cetrorelix acetate into 30% acetic acid solution (100mL) for complete dissolution, adding 600mL of water for injection, and mixing uniformly; then adding mannitol for dissolving and uniformly mixing; water for injection was added to a total volume of 1000mL to obtain a mixed solution containing mannitol and cetrorelix acetate. The solution was filtered through a 0.2 μm filter.
(2) Freezing:
subpackaging the mannitol and cetrorelix acetate solution obtained in the step (1) (subpackaging by 1.0 mL/branch) into containers, and carrying out the following steps:
the first stage is as follows: the temperature reduction rate is 0.5 ℃/min, the temperature of the plate layer is reduced to-30 ℃, and the heat preservation time is 1 hour;
and a second stage: heating the temperature of the plate layer to-10 ℃ at a heating rate of 1 ℃/min, and keeping the temperature for 1 hour;
and a third stage: the temperature of the plate layer is reduced to-40 ℃ at the temperature reduction rate of 0.5 ℃/min, and the heat preservation time is 1 hour.
(3) And (5) heating and drying.
Drying at elevated temperature, removing most of water in the primary drying stage (desorption drying), and drying at 25 deg.C to the end point in the secondary drying stage to obtain lyophilized pharmaceutical composition.
Example 2
The invention provides a preparation method of a cetrorelix preparation, which comprises the following steps:
(1) preparing a mannitol and cetrorelix acetate solution:
obtaining raw materials according to the components and the mixture ratio shown in the table 1;
adding cetrorelix acetate into 30% acetic acid solution (100mL) for complete dissolution, and then adding 600mL of water for injection for mixing uniformly; then adding mannitol for dissolving and uniformly mixing; water for injection was added to a total volume of 1000mL to obtain a mixed solution containing mannitol and cetrorelix acetate. The solution was filtered through a 0.2 μm filter.
(2) Freezing:
subpackaging the obtained mannitol and cetrorelix acetate solution (subpackaging by 1.0 mL/branch) into containers, and carrying out the following steps:
the first stage is as follows: the temperature reduction rate is 0.5 ℃/min, the temperature of the plate layer is reduced to-40 ℃, and the heat preservation time is 1 hour;
and a second stage: heating the temperature of the plate layer to-10 ℃ at a heating rate of 1 ℃/min, and keeping the temperature for 1 hour;
and a third stage: the temperature of the plate layer is reduced to-40 ℃ at the temperature reduction rate of 0.5 ℃/min, and the heat preservation time is 1 hour.
(3) And (5) heating and drying.
Drying at elevated temperature, removing most of water in the primary drying stage (desorption drying), and drying at 20 deg.C to the end point in the secondary drying stage to obtain lyophilized pharmaceutical composition.
Example 3
The invention provides a preparation method of a cetrorelix preparation, which comprises the following steps:
(1) preparing a mannitol and cetrorelix acetate solution:
obtaining raw materials according to the components and the mixture ratio shown in the table 1;
adding cetrorelix acetate into 30% acetic acid solution (100mL) for complete dissolution, adding 600mL of water for injection, and mixing uniformly; then adding mannitol for dissolving and uniformly mixing; water for injection was added to a total volume of 1000mL to obtain a mixed solution containing mannitol and cetrorelix acetate. The solution was filtered through a 0.2 μm filter.
(2) Freezing:
subpackaging the obtained mannitol and cetrorelix acetate solution (subpackaging by 1.0 mL/branch) into containers, and carrying out the following steps:
the first stage is as follows: the temperature reduction rate is 1 ℃/min, the temperature of the plate layer is reduced to-30 ℃, and the heat preservation time is 1 hour;
and a second stage: heating the temperature of the plate layer to-10 ℃ at a heating rate of 1 ℃/min, and keeping the temperature for 1 hour;
and a third stage: the temperature of the plate layer is reduced to-40 ℃ at the temperature reduction rate of 1 ℃/min, and the heat preservation time is 1 hour.
(3) And (5) heating and drying.
Drying at elevated temperature, removing most of water in the primary drying stage (desorption drying), and drying at 20 deg.C to the end point in the secondary drying stage to obtain lyophilized pharmaceutical composition.
Example 4
The invention provides a preparation method of a cetrorelix preparation, which comprises the following steps:
(1) preparing a mannitol and cetrorelix acetate solution:
obtaining raw materials according to the components and the mixture ratio shown in the table 1;
adding cetrorelix acetate into 30% acetic acid solution (100mL) for complete dissolution, adding 600mL of water for injection, and mixing uniformly; then adding mannitol for dissolving and uniformly mixing; water for injection was added to a total volume of 1000mL to obtain a mixed solution containing mannitol and cetrorelix acetate. The solution was filtered through a 0.2 μm filter.
(2) Freezing:
subpackaging the obtained mannitol and cetrorelix acetate solution (subpackaging by 1.0 mL/branch) into containers, and carrying out the following steps:
the first stage is as follows: the temperature reduction rate is 2 ℃/min, the temperature of the plate layer is reduced to-30 ℃, and the heat preservation time is 2 hours;
and a second stage: heating the temperature of the plate layer to-10 ℃ at a heating rate of 1 ℃/min, and keeping the temperature for 1 hour;
and a third stage: the temperature of the plate layer is reduced to-40 ℃ at the temperature reduction rate of 2 ℃/min, and the heat preservation time is 1 hour.
(3) And (5) heating and drying.
Drying at elevated temperature, removing most of water in the primary drying stage (desorption drying), and drying at 20 deg.C to the end point in the secondary drying stage to obtain lyophilized pharmaceutical composition.
Comparative example 1
This comparative example provides a method of preparing a cetrorelix formulation comprising the steps of:
(1) preparing a mannitol and cetrorelix acetate solution:
obtaining raw materials according to the components and the mixture ratio shown in the table 1;
adding cetrorelix acetate into 30% acetic acid solution (100mL) for complete dissolution, adding 600mL of water for injection, and mixing uniformly; then adding mannitol for dissolving and uniformly mixing; water for injection was added to a total volume of 1000mL to obtain a mixed solution containing mannitol and cetrorelix acetate. The solution was filtered through a 0.2 μm filter.
(2) Freezing:
subpackaging the obtained mannitol and cetrorelix acetate solution (subpackaging at 1.0 mL/branch) into containers, cooling the plate layer to-40 ℃ at a cooling rate of 0.5 ℃/min, and keeping the temperature for 1 hour.
(3) And (5) heating and drying.
Drying at elevated temperature, removing most of water in the primary drying stage (desorption drying), and drying at 20 deg.C to the end point in the secondary drying stage to obtain lyophilized pharmaceutical composition.
Comparative example 2
This comparative example provides a method of preparing a cetrorelix formulation comprising the steps of:
(1) preparing a mannitol and cetrorelix acetate solution:
obtaining raw materials according to the components and the mixture ratio shown in the table 1;
adding cetrorelix acetate into 30% acetic acid solution (100mL) for complete dissolution, adding 600mL of water for injection, and mixing uniformly; then adding mannitol for dissolving and uniformly mixing; water for injection was added to a total volume of 1000mL to obtain a mixed solution containing mannitol and cetrorelix acetate. The solution was filtered through a 0.2 μm filter.
(2) Freezing:
subpackaging the obtained mannitol and cetrorelix acetate solution (subpackaging at 1.0 mL/branch) into containers, cooling the temperature of the plate layer to-40 ℃ at a cooling rate of 2 ℃/min, and keeping the temperature for 1 hour.
(3) And (5) heating and drying.
Drying at elevated temperature, removing most of water in the primary drying stage (desorption drying), and drying at 20 deg.C to the end point in the secondary drying stage to obtain lyophilized pharmaceutical composition.
Test example 1
The stability of the cetrorelix preparation provided by the invention is verified.
The preparation methods provided in examples 1-4 and comparative examples 1-2 were used to prepare cetrorelix preparation products, and commercial products (MERCK) were obtained
) As a control, the stability test was performed in an accelerated test at 40 ℃ and the test results are shown in Table 2.
TABLE 2 stability test results
In the embodiment 1, in the prefreezing process, the temperature of the slab layer is firstly reduced to-30 ℃ at the cooling rate of 0.5 ℃/min, the temperature is maintained for 1 hour, then the temperature of the slab layer is increased to-10 ℃ at the heating rate of 1 ℃/min, the temperature is maintained for 1 hour, finally, the temperature of the slab layer is reduced to-40 ℃ at the cooling rate of 0.5 ℃/min, and the temperature is maintained for 1 hour, so that the sample is completely frozen. The temperature rise annealing process is adopted, the purpose is that the temperature of the composition in the penicillin bottle is raised from a crystalline state to a position between a eutectic point and a eutectic point, and then the temperature is lowered, so that the composition is subjected to a recrystallization process, crystals are uniformly distributed, the water sublimation in the freeze-drying process is accelerated, the freeze-drying preparation time is reduced, and the stability of a freeze-dried substance is improved.
Because the temperature range of the eutectic point and the eutectic point of the composition is-3 ℃ to-16 ℃, the temperature is set to be raised to-10 ℃ to ensure that the samples in the same batch are in the same state in order to ensure that the samples in the bottle are in a crystallization state and a semi-crystallization state due to the performance of a freeze dryer (slight temperature difference exists among samples in different spatial positions in a case), heat conduction between a plate layer and a penicillin bottle and the like.
From the results, it is found that the single impurity content of the conventional commercial product increases to 2.34% and the total impurity content increases to 3.9% after 6 months. Comparative example 2 is a cetrorelix preparation prepared by a process of reducing the temperature of a plate layer to-40 ℃ at a cooling rate of 2 ℃/min and keeping the temperature for 1 hour, and related substances of the cetrorelix preparation are accelerated to increase the single impurity to 0.87% and the total impurity to 2.5% after 6 months. Compared with the prior art, the comparative example 1 is that the related substances of the cetrorelix preparation prepared by the process of reducing the temperature of the plate layer to-40 ℃ at the temperature reducing rate of 0.5 ℃/min and keeping the temperature for 1 hour are accelerated to be increased to 0.51 percent after 6 months, and the total impurities are increased to 1.9 percent.
The stability of examples 1, 2, 3 and 4 is better than that of the commercial products and comparative examples 1-2. Wherein, the embodiment 1 is superior to other embodiments, the related substances have the minimum change, the stability is good, and the product is obviously superior to the products on the market.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A method for preparing a cetrorelix formulation, comprising: freezing and drying a mixed solution containing mannitol and cetrorelix acetate, wherein the freezing comprises a first stage, a second stage and a third stage;
the conditions of the first stage are as follows: cooling to-20 to-40 ℃, and then preserving heat for 0.1 to 2 hours;
the conditions of the second stage are: heating to-20 to-5 ℃, and keeping the temperature for 0.1 to 2 hours;
the conditions of the third stage are: cooling to-20-40 ℃, and then preserving heat for 0.1-2 h.
2. The method of preparing a cetrorelix formulation according to claim 1, wherein the conditions of the first stage are: cooling to-25 to-35 ℃ at a cooling rate of 0.1 to 2.5 ℃/min, and then preserving heat for 0.5 to 1 hour.
3. The method for preparing a cetrorelix formulation according to claim 2, wherein the temperature reduction rate of the first stage is 0.5 to 1.5 ℃/min.
4. The method of preparing a cetrorelix formulation according to claim 1, wherein the conditions of the second stage are: heating to-20 to-5 ℃ at a heating rate of 0.1 to 5 ℃/min, and keeping the temperature for 0.1 to 2 hours.
5. The method for preparing a cetrorelix preparation according to claim 4, wherein the temperature rise rate in the second stage is 0.5-1.5 ℃/min.
6. The process for preparing a cetrorelix formulation according to claim 1, wherein the conditions of the third stage are: cooling to-20 to-40 ℃ at a cooling rate of 0.1 to 5 ℃/min, and then preserving heat for 0.1 to 2 hours.
7. The method for preparing a cetrorelix preparation according to claim 6, wherein the temperature rise rate in the second stage is 0.1-1 ℃/min.
8. The method for preparing a cetrorelix preparation according to claim 7, further comprising filtering a mixed solution containing mannitol and cetrorelix acetate before freeze-drying;
preferably, the filter used for filtering is a 0.1-1.0 μm filter.
9. The method for preparing a cetrorelix formulation according to any one of claims 1 to 8, wherein the drying temperature is 10 to 25 ℃.
10. A cetrorelix preparation produced by the method for producing a cetrorelix preparation according to any one of claims 1 to 9.
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| CN202110113629.7A Pending CN112807418A (en) | 2021-01-27 | 2021-01-27 | Cetrorelix preparation and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113616775A (en) * | 2021-09-02 | 2021-11-09 | 南京锐志生物医药有限公司 | Cetrorelix acetate injection and preparation method thereof |
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| CN102423484A (en) * | 2011-11-23 | 2012-04-25 | 深圳翰宇药业股份有限公司 | Stable cetrorelix medicinal composition and preparation method thereof |
| WO2020254952A1 (en) * | 2019-06-17 | 2020-12-24 | Intas Pharmaceuticals Ltd. | A stable formulation of cetrorelix |
| CN114712315A (en) * | 2021-01-04 | 2022-07-08 | 齐鲁制药有限公司 | Preparation method of cetrorelix acetate freeze-dried preparation |
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| CN102423484A (en) * | 2011-11-23 | 2012-04-25 | 深圳翰宇药业股份有限公司 | Stable cetrorelix medicinal composition and preparation method thereof |
| WO2020254952A1 (en) * | 2019-06-17 | 2020-12-24 | Intas Pharmaceuticals Ltd. | A stable formulation of cetrorelix |
| CN114712315A (en) * | 2021-01-04 | 2022-07-08 | 齐鲁制药有限公司 | Preparation method of cetrorelix acetate freeze-dried preparation |
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| SHIRIN HOOSHFAR ET AL.: "Development and Validation of a Reversed-phase HPLC Method for Assay of the Decapeptide Cetrorelix Acetate in Bulk and Pharmaceutical Dosage Forms", IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113616775A (en) * | 2021-09-02 | 2021-11-09 | 南京锐志生物医药有限公司 | Cetrorelix acetate injection and preparation method thereof |
| CN113616775B (en) * | 2021-09-02 | 2024-01-30 | 南京锐志生物医药有限公司 | Cetrorelix acetate injection and preparation method thereof |
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