CN116115561A

CN116115561A - Tranexamic acid injection and preparation method thereof

Info

Publication number: CN116115561A
Application number: CN202310262843.8A
Authority: CN
Inventors: 杜玮丽
Original assignee: Hunan Haosen Pharmaceutical Co ltd
Current assignee: Hunan Haosen Pharmaceutical Co ltd
Priority date: 2023-03-17
Filing date: 2023-03-17
Publication date: 2023-05-16

Abstract

The invention provides an tranexamic acid injection and a preparation method thereof, belonging to the technical field of pharmaceutical preparations, and comprising the following steps: s1, preparing a liquid medicine; s2, ampoule treatment; s3, filling, nitrogen filling, sealing, sterilizing and packaging. The method of the invention does not need to carry out activated carbon adsorption and metal ion chelating agent catalysis, simplifies the production process, reduces the production cost, and has the advantages of stable product quality, less impurities and the like, thereby having wide application prospect.

Description

Tranexamic acid injection and preparation method thereof

Technical Field

The invention relates to the technical field of pharmaceutical preparations, in particular to tranexamic acid injection and a preparation method thereof.

Background

Tranexamic acid, also called tranexamic acid, is an antiplasmin-dissolving amino acid, and is one of the commonly used anticoagulants in clinic. Normal blood circulation in humans is maintained primarily by the balance between coagulation and fibrinolytic systems. Tranexamic acid can competitively resist plasmin activating factor, so that plasminogen can not be converted into plasmin, and has the functions of stopping bleeding and diminishing inflammation. Clinically, it is mainly used for various hemorrhages caused by fibrinolysis hypersolubility. At present, researches show that the tranexamic acid has good curative effect and tolerance on treating menorrhagia, chloasma and the like, has wide clinical range, and can achieve good hemostatic effect on various blood symptoms without vascular irritation and anaphylaxis.

The invention patent with publication number of CN110237029A discloses that the catalysis of metal ions on tranexamic acid is effectively controlled by adding edetate disodium calcium (CaNa 2-EDTA) into the prescription, so that the generation of isomer impurities is reduced, and the quality of injection is improved. The invention patent with publication number of CN102973501B adopts activated carbon adsorption, removes pyrogen and metal ions through activated carbon adsorption, then uses acetone, ethanol and ethylenediamine tetraacetic acid aqueous solution to wash and dry the activated carbon for the needle so as to remove the metal and other impurities remained in the activated carbon for the needle, reduce the generation of impurity-z-isomer and ensure the quality of tranexamic acid injection. The invention patent with publication number CN110876718A adopts 10% dilute hydrochloric acid or 1% sodium hydroxide solution to adjust the pH value, thereby effectively simplifying the production process and ensuring the quality and clinical safety of the product.

None of the above methods can completely guarantee the quality of the injection, and has the disadvantages of complex process, high production cost and possible risk of introducing impurities.

Disclosure of Invention

The invention aims to provide an tranexamic acid injection and a preparation method thereof, and the tranexamic acid injection has the advantages of high purity and stable product quality.

The technical scheme of the invention is realized as follows:

the invention provides a preparation method of tranexamic acid injection, which comprises the following steps:

s1, configuration: measuring 70-80 ℃ water for injection with 60-62% of the prescription amount, slowly adding tranexamic acid while stirring to dissolve the tranexamic acid, continuously stirring and circulating, and adding water for injection to the full amount to obtain a liquid medicine; the liquid medicine is filtered back through a filter element, and the pH value is controlled to be 7.0-8.0; filtering the liquid medicine into a liquid storage tank, and preserving the heat of the liquid medicine in the whole process; filtering the liquid medicine in the liquid tank through a 0.22 mu m polyether sulfone filter membrane, and preserving heat in the whole process of filtering; inputting the liquid storage container for filling; s2, ampoule treatment: cleaning ampoule, putting into a sterilizing and drying oven at 120-124 deg.C, sterilizing by dry heat, and charging nitrogen;

s3, filling, nitrogen filling, sealing, sterilizing and packaging.

As a further improvement of the invention, the temperature of the liquid medicine after being filtered into the liquid storage tank is controlled to be 40-60 ℃.

As a further improvement of the invention, the stirring circulation time is 5-15 minutes after the tranexamic acid is dissolved.

As a further development of the invention, the filter element is a 0.45 μm and 0.22 μm polyethersulfone filter element.

As a further improvement of the invention, the temperature of the liquid medicine after being filtered into the liquid storage tank is 40-60 ℃.

As a further improvement of the invention, the ampoule nitrogen filling time is 0.5-2min.

As a further improvement of the invention, the nitrogen charging time in the step S3 is 0.5-2min.

The invention further protects the tranexamic acid injection prepared by the method.

The invention has the following beneficial effects:

according to the invention, the filter element is cleaned and sterilized to reduce the generation of impurities and ensure the uniform mixing of the liquid medicine by increasing the filtering cycle time; the invention prevents the breeding and pollution of microorganisms by preserving the temperature of 40-60 ℃ in the whole process of the liquid medicine, and ensures the qualification of bacterial endotoxin; the invention is realized by filling N ₂ Filling, preventing oxidation and reducing impurity generation; the invention does not need the adsorption of active carbon, simplifies the production process, reduces the production difficulty and the production cost, is beneficial to environmental protection, reduces the labor intensity and meets the quality requirements.

Description of the embodiments

The following description of the technical solutions in the embodiments of the present invention will be clear and complete, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

Examples

3000ml of water for injection was added to the preparation tank, stirring was turned on, and the temperature of the water for injection was controlled at 75 ℃. Slowly adding 250g of tranexamic acid raw material into a diluting tank while stirring to dissolve the tranexamic acid raw material, continuously stirring and circulating for 10 minutes, adding 2000ml of water for injection, and stirring for 15 minutes to make the tranexamic acid raw material uniform. The liquid medicine is filtered in a diluting tank through a 0.45 mu m and a 0.22 mu m PES (polyether sulfone) filter membrane. Filtering the liquid medicine into a liquid storage tank, and preserving the temperature of the liquid medicine at 50 ℃ in the whole process. The liquid medicine in the liquid tank is filtered by a 0.22 mu m PES (polyether sulfone) filter membrane, and the whole process of the liquid medicine is kept at 50 ℃. Inputting into a filling liquid storage container for filling. Filling, sealing and sterilizing: setting the sterilizing temperature at 121 ℃ and sterilizing for 15min. Filling nitrogen into ampoule for 30s before and after filling, sealing, sterilizing and packaging.

This comparative example differs from example 1 only in that a nylon membrane was used instead of a polyethersulfone filter.

This comparative example differs from example 1 only in that a polyvinylidene fluoride membrane was used instead of a polyethersulfone filter membrane.

This comparative example differs from example 1 only in that a mixed cellulose ester was used instead of the polyethersulfone filter.

This comparative example differs from example 1 only in that polypropylene was used instead of polyethersulfone filter membranes.

This comparative example differs from example 1 only in that polytetrafluoroethylene was used instead of polyethersulfone filter membranes.

This comparative example differs from example 1 only in that no nitrogen is added.

Example 2:

3000ml of water for injection was added to the preparation tank, stirring was turned on, and the temperature of the water for injection was controlled at 75 ℃. Slowly adding 250g of tranexamic acid raw material into a diluting tank while stirring to dissolve the tranexamic acid raw material, continuously stirring and circulating for 10 minutes, adding 2000ml of water for injection, and stirring for 15 minutes to make the tranexamic acid raw material uniform. The liquid medicine is filtered in a diluting tank through a 0.45 mu m and a 0.22 mu m PES (polyether sulfone) filter membrane. Filtering the liquid medicine into a liquid storage tank, and preserving the temperature of the liquid medicine at 50 ℃ in the whole process. The liquid medicine in the liquid tank is filtered by a 0.22 mu m PES (polyether sulfone) filter membrane, and the whole process of the liquid medicine is kept at 50 ℃. Inputting into a filling liquid storage container for filling. Filling, sealing and sterilizing: setting the sterilizing temperature at 121 ℃ and sterilizing for 15min. Filling nitrogen into ampoule for 1min before and after filling, sealing, sterilizing, and packaging.

Example 3:

3000ml of water for injection was added to the preparation tank, stirring was turned on, and the temperature of the water for injection was controlled at 75 ℃. Slowly adding 250g of tranexamic acid raw material into a diluting tank while stirring to dissolve the tranexamic acid raw material, continuously stirring and circulating for 10 minutes, adding 2000ml of water for injection, and stirring for 15 minutes to make the tranexamic acid raw material uniform. The liquid medicine is filtered in a diluting tank through a 0.45 mu m and a 0.22 mu m PES (polyether sulfone) filter membrane. Filtering the liquid medicine into a liquid storage tank, and preserving the temperature of the liquid medicine at 50 ℃ in the whole process. The liquid medicine in the liquid tank is filtered by a 0.22 mu m PES (polyether sulfone) filter membrane, and the whole process of the liquid medicine is kept at 50 ℃. Inputting into a filling liquid storage container for filling. Filling, sealing and sterilizing: setting the sterilizing temperature at 121 ℃ and sterilizing for 15min. Filling nitrogen into ampoule for 2min before and after filling, sealing, sterilizing, and packaging.

The sample was checked for visible foreign matter and the intermediate tranexamic acid content and pH were measured, and the results are shown in Table 1.

TABLE 1

The nylon membrane and the insoluble fine particles of the mixed cellulose ester used in comparative example 1 and comparative example 3 were not acceptable and the impurity content was high; whereas comparative examples 2, 4 and 5 have higher impurity contents and are costly than example 1. In comparative example 6, nitrogen is not filled, impurities are increased, pH is lowered, and nitrogen is filled to protect the catalyst, so that oxidation is prevented, and impurity generation is reduced.

The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.

Claims

1. The preparation method of the tranexamic acid injection is characterized by comprising the following steps:

s1, configuration: measuring 70-80 ℃ water for injection with 60-62% of the prescription amount, slowly adding tranexamic acid while stirring to dissolve the tranexamic acid, continuously stirring and circulating, and adding water for injection to the full amount to obtain a liquid medicine; the liquid medicine is filtered back through a filter element, and the pH value is controlled to be 7.0-8.0; filtering the liquid medicine into a liquid storage tank, and preserving the heat of the liquid medicine in the whole process; filtering the liquid medicine in the liquid tank through a 0.22 mu m polyether sulfone filter membrane, and preserving heat in the whole process of filtering; inputting the liquid storage container for filling;

s2, ampoule treatment: cleaning ampoule, putting into a sterilizing and drying oven at 120-124 deg.C, sterilizing by dry heat, and charging nitrogen;

s3, filling, nitrogen filling, sealing, sterilizing and packaging.

2. The method for preparing tranexamic acid injection according to claim 1, wherein the temperature of the liquid medicine after filtration into the liquid storage tank is controlled to be 40-60 ℃.

3. The method for preparing tranexamic acid injection according to claim 1, wherein the continuous stirring cycle time after the tranexamic acid is dissolved is 5-15 minutes.

4. The method for preparing tranexamic acid injection according to claim 1, wherein the filter element is a polyether sulfone filter element of 0.45 [ mu ] m and 0.22 [ mu ] m.

5. The method for preparing tranexamic acid injection according to claim 1, wherein the temperature of the liquid medicine after filtration into the liquid storage tank is 40-60 ℃.

6. The method for preparing tranexamic acid injection according to claim 1, wherein the ampoule nitrogen filling time is 0.5-2min.

7. The method for preparing tranexamic acid injection according to claim 1, wherein the nitrogen charging time in step S3 is 0.5-2min.

8. An tranexamic acid injection prepared by the preparation method according to any one of claims 1 to 7.