Lornoxicam freeze-dried product for injection and preparation method of lornoxicam freeze-dried product
By adding polyvinylpyrrolidone and trehalose as protective agents to lonoxicam injection and optimizing the lyophilized process, the problem of high impurity content in lyophilizedamide products for a long time is solved, and the stability and production efficiency of the product are improved.
Patent Information
- Application Number
- CN202510668939.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-23
- Publication Date
- 2025-08-12
AI Technical Summary
The existing lyophilized lyophilized products for injection have high impurities during long-term storage, the lyophilized process is complex and costly, which affects product quality and stability.
Polyvinylpyrrolidone and trehalose are added as protective agents to lonoxicam injection. Combined with specific lyophilized process parameters, the stability of the drug structure is maintained through hydrogen bonding and complexation, preventing drug aggregation, forming a uniform and delicate lyophilized product structure, and reducing impurity content.
It improves the stability and resolubility of lyophilized lyophilized products, reduces impurity content, shortens production time, reduces costs, and is suitable for industrial production.
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Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of pharmaceutical preparations, in particular to a lyophilized product of lornoxicam for injection and a preparation method thereof. Background Art
[0002] Lomoxican for injection is a non-opioid analgesic and a nonsteroidal anti-inflammatory drug (NSAIDS) in the oxicam class. Chemically classified as an enolic acid derivative, its primary mechanism of action is to inhibit cyclooxygenase (COX) activity, thereby inhibiting prostaglandin synthesis, thereby achieving anti-inflammatory and analgesic effects. Lomoxican for injection exhibits strong anti-inflammatory and analgesic effects, a short half-life, and good tolerability. It is widely used clinically to treat mild to moderate postoperative pain, as well as various acute and chronic pain conditions.
[0003] The production of lornoxicam for injection is usually carried out by aseptic lyophilization technology on the market. However, in order to reduce the moisture content in the finished product, the existing lornoxicam for injection lyophilization method generally needs to go through multiple cooling, heating and heat preservation processes, with many temperature gradients, large changes in vacuum degree, complicated processes, long freeze-drying process processing time, and high production cost. In addition, the complicated heating and cooling processes and the extension of the processing time may cause the increase of impurity content in the lornoxicam for injection lyophilized product. Therefore, there is an urgent need to develop a lornoxicam for injection lyophilized product with stable product quality and less impurity content during storage. Summary of the Invention
[0004] Aiming at the problem that the existing lyophilized lornoxicam for injection has a high impurity content after long-term storage, the present invention provides a lyophilized lornoxicam for injection and a preparation method thereof. A specific protective agent is added to the lornoxicam injection, which can better maintain the structure and activity of lornoxicam during the lyophilization process and improve its stability. Combined with the parameter setting of the lyophilization process, the impurity content in the lyophilized lornoxicam for injection after long-term storage is further reduced.
[0005] In order to solve the above technical problems, the technical solution provided by the present invention is: In a first aspect, the present invention provides a lyophilized product of lornoxicam for injection, comprising the following raw materials: lornoxicam, mannitol, tromethamine, disodium edetate and a protective agent; The protective agent includes polyvinyl pyrrolidone and trehalose.
[0006] Compared with the prior art, the present invention provides a lyophilized product of lornoxicam for injection (hereinafter referred to as lyophilized product). Lornoxicam is a poorly soluble drug. Polyvinylpyrrolidone (PVP) can form hydrogen bonds or complexes with lornoxicam molecules through the hydrophilic groups in its molecules, thereby increasing the solubility of lornoxicam in water and enabling the drug to be better dispersed evenly in the solution state before lyophilization. In the process of preparing the lyophilized product of lornoxicam for injection, PVP can prevent the aggregation and precipitation of lornoxicam particles, allowing the drug particles to be evenly suspended in the solution, which is beneficial to maintaining the uniformity of the drug during the lyophilization process, inhibiting the aggregation and crystallization of drug molecules, maintaining the amorphous state of the drug, improving the appearance of the lyophilized product, and making the lyophilized product more uniform. In the freeze-drying process, trehalose can form a relatively loose and uniform structure by forming hydrogen bonds with lornoxicam molecules, thereby replacing water molecules and binding to polar groups on the surface of drug molecules, thereby preventing the structural changes of drug molecules caused by the loss of water molecules, maintaining the natural conformation of the drug, and ensuring its activity and stability; trehalose helps to form a uniform and delicate freeze-dried product structure, making the surface of the freeze-dried product smooth, the texture loose, and the appearance good; trehalose can increase the glass transition temperature of the freeze-dried product, making the product less likely to undergo glass transition during storage and in a stable glass state, thereby reducing the movement of drug molecules and the occurrence of degradation reactions, and extending the shelf life of the product.
[0007] In addition, during the storage of freeze-dried products, PVP and trehalose can form a protective film around the lornoxicam drug molecules, reducing the contact of the drug with external environmental factors (such as oxygen, moisture, light, etc.), reducing the possibility of drug degradation reactions such as oxidation and hydrolysis, and at the same time reducing the mutual collision and aggregation between drug molecules, avoiding the reduction of drug effectiveness and stability due to aggregation, so that the drug can maintain a good dispersion state after freeze-drying; during re-dissolution, this structure is conducive to the rapid penetration of water into the freeze-dried product, accelerating the dissolution of the drug, improving the re-dissolution speed and solubility of the freeze-dried product, so that the drug can quickly reach the concentration required for clinical use and produce good therapeutic effects.
[0008] Preferably, the mass ratio of polyvinyl pyrrolidone to trehalose is (3-6):1.
[0009] The present invention has found through a large number of experiments that when the mass ratio of polyvinyl pyrrolidone to trehalose is within the above range, the synergistic effect of the protective agent can be further exerted, and the quality stability of the freeze-dried product can be further ensured.
[0010] Preferably, the lyophilized product of lornoxicam for injection comprises the following raw materials in parts by mass: 7 to 9 parts of lornoxicam, 90 to 110 parts of mannitol, 11 to 13 parts of tromethamine, 0.15 to 0.25 parts of disodium edetate, 3 to 5 parts of a protective agent, and 1900 to 2000 parts of water.
[0011] By limiting the amount of each raw material (especially the amount of the protective agent), the present invention can better exert the synergistic effect of polyvinyl pyrrolidone and trehalose in the protective agent, thereby further improving the quality and stability of the freeze-dried product.
[0012] In a second aspect, the present invention provides a method for preparing the lyophilized product of lornoxicam for injection, comprising the following steps: S1, pre-freezing the lornoxicam solution at -25°C to -20°C, and then freezing the resulting suspension material at -55°C to -50°C to obtain a frozen solid; S2. Under a vacuum degree of 10 Pa to 20 Pa, the frozen solid is subjected to sublimation drying at -10°C to -5°C, and then subjected to desorption drying at 25°C to 30°C to obtain a lyophilized product of lornoxicam for injection.
[0013] The preparation method of the lyophilized product of lornoxicam for injection provided by the present invention comprises the following steps: pre-freezing is performed at a specific temperature so that the lornoxicam liquid is in a "supercooling" stage, the lornoxicam liquid is gradually frozen to form lyophilized crystals, tiny crystals are combined with each other to form irregular large-particle crystals, sublimation channels are formed between the large-particle crystals, and a relatively large and uniform crystal form is formed. The crystal has a specific structure, the sublimation drying channel of water in the subsequent sublimation drying process is increased, the temperature can be tolerated better, and the sublimation rate is accelerated in the subsequent sublimation drying process.
[0014] In the process of preparing the lyophilized product of lornoxicam for injection, PVP, sodium alginate and mannitol work synergistically to prevent the aggregation and crystallization of lornoxicam particles, so that the drug particles can be evenly suspended in the drug solution, which is beneficial to maintaining the uniformity of the drug during the freeze-drying process and preventing the structural changes of the drug molecules due to the loss of water molecules; at the same time, through the synergistic effect of sodium alginate and mannitol, a uniform, delicate, loose and uniform lyophilized product structure is formed with a loose texture, thereby improving the activity and stability of the lyophilized product.
[0015] Preferably, in S1, the method for preparing the lornoxicam solution comprises the following steps: Add 75% to 85% of the prescription amount of water for injection, disodium edetate, tromethamine, lornoxicam, mannitol and a protective agent to the preparation tank in sequence, mix evenly, add water for injection to the total amount of preparation, filter, and obtain the lornoxicam liquid.
[0016] The present invention provides a preparation method of lornoxicam liquid. By controlling the order of adding various raw materials and the distribution ratio of water for injection, the solubility of the injection liquid is further improved, precipitation is avoided, the long-term stability of the freeze-dried product after subsequent freeze-drying is facilitated, the increase of impurity content in the freeze-dried product is controlled, and thus the quality and efficacy of the freeze-dried product are effectively improved.
[0017] Further preferably, in S1, the filtration uses a two-stage polyethersulfone filter element.
[0018] For example, in S1, the pore size of the first-stage polyethersulfone filter element in the two-stage polyethersulfone filter element is 0.45µm, and the pore size of the second-stage polyethersulfone filter element is 0.22µm.
[0019] The present invention adopts a two-stage polyethersulfone filter element with a specific pore size for sequential filtration, which can not only ensure that the bacteria and endotoxin content of the product are qualified, but also ensure that the particles and visible foreign matter of the product are qualified. In addition, no activated carbon is used in the production process, which reduces the pollution to the production clean area, alleviates the environmental pressure, and also reduces the impurities and insoluble particles that may be introduced by the activated carbon, which is conducive to further improving the effectiveness, safety and stability of product quality.
[0020] For example, in S1, the lornoxicam solution can be poured into a medium borosilicate glass controlled injection bottle, and the dosage can be 8.6 mg of lornoxicam per bottle, and then the subsequent pre-freezing step is performed.
[0021] Preferably, in S1, the pH of the lornoxicam solution is 8.5-9.
[0022] Preferably, in S1, the temperature is lowered to -25°C to -20°C by programmed cooling, with a cooling rate of 0.5°C / min to 1°C / min.
[0023] Preferably, in S1, the pre-freezing time is 30 min to 50 min.
[0024] Preferably, in S1, the temperature is lowered to -55°C to -50°C by programmed cooling, with a cooling rate of 0.5°C / min to 1°C / min.
[0025] Preferably, in S1, the freezing time is 30 min to 60 min.
[0026] The present invention limits the conditions of pre-freezing and freezing, thereby ensuring that a suspension material with uniform solute and specific structure is formed in the pre-freezing stage, and then the suspension material is gradually frozen solid, which is beneficial to the subsequent sublimation drying and analytical drying.
[0027] Preferably, in S2, the temperature is raised to -10°C to -5°C by programmed heating, with a heating rate of 1°C / min to 2°C / min.
[0028] Preferably, in S2, the sublimation drying time is 2h~3h.
[0029] Preferably, in S2, the temperature is raised to 25°C to 30°C by programmed heating, with a heating rate of 1°C / min to 2°C / min.
[0030] Preferably, in S2, the time for the analytical drying is 1 h to 2 h.
[0031] The present invention controls the conditions of sublimation drying and can ensure that free water in the material is removed by only adopting a one-stage design, thereby greatly shortening the time of the existing sublimation drying stage, improving production efficiency, and saving production costs; the present invention can further ensure that bound water in the material is effectively removed by controlling the conditions of analytical drying.
[0032] Compared with the prior art, the present invention has the following beneficial effects: (1) The present invention uses polyvinyl pyrrolidone and trehalose in a specific ratio as protective agents, which have the effects of improving the biocompatibility and solubility of drugs, solubilizing and suspending, maintaining the stability of drug structure, inhibiting drug aggregation, increasing the glass transition temperature, improving the appearance and texture of freeze-dried products, and enhancing the resolubility of freeze-dried products; (2) The preparation method of the lyophilized product of lornoxicam for injection provided by the present invention improves the storage stability of the lyophilized product, and the increase of the impurity content in the stability and acceleration tests is not obvious. It also shortens the production time, improves the production efficiency, reduces the production cost, facilitates the realization of industrial production, and has broad application prospects. DETAILED DESCRIPTION
[0033] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.
[0034] In the present invention, materials not otherwise specified are all commercially available products.
[0035] Example 1 This embodiment provides a lyophilized product of lornoxicam for injection, with the following dosage: lornoxicam 8g, mannitol 100g, tromethamine 12g, edetate disodium 0.2g, a protective agent 4g, and water for injection (based on a total mass of 2kg). The protective agent is composed of polyvinyl pyrrolidone and trehalose in a mass ratio of 5:1.
[0036] The preparation method of the above-mentioned lornoxicam lyophilized product for injection comprises the following steps: Sa, weigh each prescription component according to the designed ratio, add 80% of the prescription amount of water for injection, edetate disodium, tromethamine, lornoxicam, mannitol and protective agent into the preparation tank in sequence, add water for injection to the total amount of preparation, stir evenly in sequence, and then filter with a secondary polyethersulfone filter element to obtain lornoxicam solution.
[0037] Sb. Pour the lornoxicam solution into a medium borosilicate glass controlled injection bottle with a dosage of 8.6 mg of lornoxicam per vial, and semi-stopper the vial; cool the injection bottle containing the lornoxicam solution to -22°C at a rate of 0.8°C / min for pre-freezing, and keep warm for 40 minutes. Then, cool the resulting suspension material to -52°C at a rate of 0.7°C / min for freezing, and keep warm for 45 minutes to obtain a frozen solid.
[0038] Sc. Under a vacuum degree of 15 Pa, the frozen solid was heated to -8 ° C at a rate of 1.5 ° C / min for sublimation drying. After keeping warm for 2.5 hours, the temperature was raised to 28 ° C at a rate of 1.5 ° C / min for desorption drying. After keeping warm for 1.5 hours, nitrogen was filled into the injection bottle and the stopper was pressed to obtain the lyophilized product of lornoxicam for injection.
[0039] Example 2 This embodiment provides a lyophilized product of lornoxicam for injection, with the following dosage: 7.2 g of lornoxicam, 90 g of mannitol, 11 g of tromethamine, 0.15 g of edetate disodium, 3.2 g of a protective agent, and water for injection (based on a total mass of 2 kg). The protective agent is composed of polyvinyl pyrrolidone and trehalose in a mass ratio of 3:1.
[0040] The preparation method of the above-mentioned lornoxicam lyophilized product for injection comprises the following steps: Sa, weigh each prescription component according to the designed ratio, add 75% of the prescription amount of water for injection, edetate disodium, tromethamine, lornoxicam, mannitol and protective agent into the preparation tank in sequence, add water for injection to the total amount of preparation, stir evenly in sequence, and then filter with a secondary polyethersulfone filter element to obtain lornoxicam solution.
[0041] Sb. Pour the lornoxicam solution into a medium borosilicate glass controlled injection bottle with a dosage of 8.4 mg of lornoxicam per bottle, and semi-stopper it; cool the injection bottle containing the lornoxicam solution to -20°C at a rate of 1°C / min for pre-freezing, keep it warm for 50 minutes, and then cool the resulting suspension material to -50°C at a rate of 0.5°C / min for freezing. After keeping it warm for 30 minutes, a frozen solid is obtained.
[0042] Sc. Under a vacuum degree of 10 Pa, the frozen solid was heated to -5°C at a rate of 1°C / min for sublimation drying. After keeping warm for 2 hours, the temperature was raised to 25°C at a rate of 2°C / min for desorption drying. After keeping warm for 2 hours, nitrogen was filled into the injection bottle and the stopper was pressed to obtain the lyophilized product of lornoxicam for injection.
[0043] Example 3 This embodiment provides a lyophilized product of lornoxicam for injection, with the following dosage: lornoxicam 8.8g, mannitol 110g, tromethamine 13g, edetate disodium 0.25g, a protective agent 4.8g, and water for injection (based on a total mass of 2kg). The protective agent is composed of polyvinylpyrrolidone and trehalose in a mass ratio of 6:1.
[0044] The preparation method of the above-mentioned lornoxicam lyophilized product for injection comprises the following steps: Sa, weigh each prescription component according to the designed ratio, add 85% of the prescription amount of water for injection, edetate disodium, tromethamine, lornoxicam, mannitol and protective agent into the preparation tank in sequence, add water for injection to the total amount of preparation, stir evenly in sequence, and then filter with a secondary polyethersulfone filter element to obtain lornoxicam solution.
[0045] Sb. Pour the lornoxicam solution into a medium borosilicate glass controlled injection bottle with a dosage of 8.8 mg of lornoxicam per bottle, and semi-stopper it; cool the injection bottle containing the lornoxicam solution to -25°C at a rate of 0.5°C / min for pre-freezing, keep it warm for 30 minutes, and then cool the resulting suspension material to -55°C at a rate of 1°C / min for freezing. After keeping it warm for 60 minutes, a frozen solid is obtained.
[0046] Sc. Under a vacuum degree of 20 Pa, the frozen solid was heated to -10 ° C at a rate of 2 ° C / min for sublimation drying. After keeping warm for 3 hours, the temperature was raised to 30 ° C at a rate of 1 ° C / min for desorption drying. After keeping warm for 1 hour, nitrogen was filled into the injection bottle and the stopper was pressed to obtain the lyophilized product of lornoxicam for injection.
[0047] Example 4 This embodiment provides a lyophilized product of lornoxicam for injection, which is similar to that of Example 1, except that the protective agent is composed of polyvinyl pyrrolidone and trehalose in a mass ratio of 1:1. The remaining components and contents are the same as those of Example 1 and are not described again.
[0048] The preparation method of the above-mentioned lyophilized product of lornoxicam for injection is the same as that in Example 1 and will not be repeated here.
[0049] Example 5 This embodiment provides a lyophilized product of lornoxicam for injection, which is similar to that of Example 1, except that the protective agent is composed of polyvinyl pyrrolidone and trehalose in a mass ratio of 10:1. The remaining components and contents are the same as those of Example 1 and are not described again.
[0050] The preparation method of the above-mentioned lyophilized product of lornoxicam for injection is the same as that in Example 1 and will not be repeated here.
[0051] Example 6 This embodiment provides a lyophilized product of lornoxicam for injection, which is similar to Example 1, except that the mass of the protective agent is 10 g and the mass of the water for injection is reduced accordingly. The remaining components and contents are the same as those in Example 1 and will not be repeated here.
[0052] The preparation method of the above-mentioned lyophilized product of lornoxicam for injection is the same as that in Example 1 and will not be repeated here.
[0053] Comparative Example 1 This comparative example provides a lyophilized product of lornoxicam for injection, which is similar to Example 1, except that polyvinyl pyrrolidone is replaced with trehalose of equal mass. The remaining components and contents are the same as those in Example 1 and are not described again.
[0054] The preparation method of the above-mentioned lyophilized product of lornoxicam for injection is the same as that in Example 1 and will not be repeated here.
[0055] Comparative Example 2 This comparative example provides a lyophilized product of lornoxicam for injection, which is similar to Example 1, except that trehalose is replaced with polyvinylpyrrolidone of equal mass. The remaining components and contents are the same as those in Example 1 and are not described again.
[0056] The preparation method of the above-mentioned lyophilized product of lornoxicam for injection is the same as that in Example 1 and will not be repeated here.
[0057] Comparative Example 3 This comparative example provides a lyophilized product of lornoxicam for injection, which is similar to Example 1, except that polyvinyl pyrrolidone is replaced with polyethylene glycol (PEG) of equal mass. The remaining components and contents are the same as those in Example 1 and are not described again.
[0058] The preparation method of the above-mentioned lyophilized product of lornoxicam for injection is the same as that in Example 1 and will not be repeated here.
[0059] Comparative Example 4 This comparative example provides a lyophilized product of lornoxicam for injection, which is similar to Example 1, except that trehalose is replaced with mannitol of equal mass. The remaining components and contents are the same as those in Example 1 and are not described again.
[0060] The preparation method of the above-mentioned lyophilized product of lornoxicam for injection is the same as that in Example 1 and will not be repeated here.
[0061] Comparative Example 5 This comparative example provides a lyophilized product of lornoxicam for injection, which is similar to Example 1, except that the protective agent is replaced with water for injection of equal quality. The remaining components and contents are the same as those in Example 1 and are not described again.
[0062] The preparation method of the above-mentioned lyophilized product of lornoxicam for injection is similar to that of Example 1, except that the addition of the protective agent is omitted and will not be described in detail.
[0063] Comparative Example 6 This comparative example provides a method for preparing a lyophilized product of lornoxicam for injection, which is similar to Example 1, except that the pre-freezing and freezing temperatures are interchanged in Sb. Specifically, the method comprises the following steps: Sa is the same as Sa in Example 1 and will not be described in detail.
[0064] Sb. Pour the lornoxicam solution into a medium borosilicate glass controlled injection bottle with a dosage of 8.6 mg of lornoxicam per vial, and semi-stopper the vial; cool the injection bottle containing the lornoxicam solution to -52°C at a rate of 0.8°C / min for pre-freezing, and after keeping warm for 40 minutes, heat the resulting suspension material to -22°C at a rate of 0.7°C / min for freezing, and after keeping warm for 45 minutes, obtain a frozen solid.
[0065] Sc. is the same as Sc in Example 1 and will not be described in detail.
[0066] The prescription of the injection is exactly the same as that of Example 1 and will not be repeated here.
[0067] Comparative Example 7 This comparative example provides a preparation method of a lyophilized product of lornoxicam for injection, which is similar to Example 1, except that the product is frozen at -52°C for 85 minutes in Sb, omitting pre-freezing. Specifically, the following steps are included: Sa is the same as Sa in Example 1 and will not be described in detail.
[0068] Sb. Pour the lornoxicam solution into a medium borosilicate glass controlled injection bottle with a dosage of 8.6 mg of lornoxicam per bottle, and half-stopper it; cool the injection bottle containing the lornoxicam solution to -52°C at a rate of 0.8°C / min and freeze it. After keeping warm for 85 minutes, a frozen solid is obtained.
[0069] Sc. is the same as Sc in Example 1 and will not be described in detail.
[0070] The prescription of the injection is exactly the same as that of Example 1 and will not be repeated here.
[0071] Comparative Example 8 This comparative example provides a preparation method of lyophilized lornoxicam for injection, which is similar to Example 1, except that the sublimation drying temperature in Sc is 2°C. The method specifically comprises the following steps: Sa~Sb are the same as Sa~Sb in Example 1 and will not be described in detail.
[0072] Sc. Under a vacuum degree of 15 Pa, the frozen solid was heated to 2°C at a rate of 1.5°C / min for sublimation drying. After keeping warm for 2.5 hours, the temperature was raised to 28°C at a rate of 1.5°C / min for desorption drying. After keeping warm for 1.5 hours, nitrogen was filled into the injection bottle and the stopper was pressed to obtain the lyophilized product of lornoxicam for injection.
[0073] The prescription of the injection is exactly the same as that of Example 1 and will not be repeated here.
[0074] Verification test The lyophilized products of lornoxicam for injection provided in Examples 1 to 6 and Comparative Examples 1 to 8 were subjected to accelerated tests at 40 ° C ± 2 ° C and RH = 75% ± 5% to test the lornoxicam content, reconstitution time and impurities of the lyophilized products (according to the requirements of the 2020 edition of the Chinese Pharmacopoeia). The results are shown in Table 1.
[0075] Table 1 Accelerated test results of lornoxicam lyophilized product for injection
[0076] The single impurities in Table 1 include impurities I to VIII and unknown impurities. The information of the single impurities is as follows: Impurity I is 2-aminopyridine, with a molecular formula of C5H6N2; Impurity II is N-(2-pyridyl)acetamidic acid, with a molecular formula of C7H6N2O3; Impurity IV is 5-chloro-3-sulfinic acid-2-thiophenecarboxylic acid, with a molecular formula of C5H3ClO4S2; Impurity VI is tenoxicam, with a molecular formula of C 13 H 11 N3O4S2; Impurity VII is 5-chloro-3-sulfinyl N-[tris(hydroxy-methyl)methyl]thiophene-2-carboxamide, with the molecular formula C9H 12 ClNO6S2.
[0077] It can be seen from the above test data that, compared with Comparative Examples 1 to 8, the lyophilized products of lornoxicam for injection prepared in Examples 1 to 6 of the present invention have lower impurity content and higher stability. The increase in impurity content during the accelerated 6-month and accelerated 12-month tests is significantly lower than that in Comparative Examples 1 to 8. This proves that the lyophilized products of lornoxicam for injection prepared in the examples of the present invention are of better quality, have better stability and safety, and are therefore more conducive to improving the safety of clinical application.
[0078] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.
Claims
1. A lyophilized product of lornoxicam for injection, characterized in that: The invention comprises the following raw materials: lornoxicam, mannitol, tromethamine, edetate disodium and protective agent; The protective agent includes polyvinyl pyrrolidone and trehalose.
2. The lyophilized product of lornoxicam for injection according to claim 1, wherein The mass ratio of the polyvinyl pyrrolidone to trehalose is (3-6):
1.
3. The lyophilized product of lornoxicam for injection according to claim 1, wherein The lyophilized product of lornoxicam for injection comprises the following raw materials in parts by mass: 7 to 9 parts of lornoxicam, 90 to 110 parts of mannitol, 11 to 13 parts of tromethamine, 0.15 to 0.25 parts of disodium edetate, 3 to 5 parts of a protective agent, and 1900 to 2000 parts of water.
4. The method for preparing the lyophilized product of lornoxicam for injection according to any one of claims 1 to 3, characterized in that: The steps include: S1, pre-freezing the lornoxicam solution at -25°C to -20°C, and then freezing the resulting suspension material at -55°C to -50°C to obtain a frozen solid; S2. Under a vacuum degree of 10 Pa to 20 Pa, the frozen solid is subjected to sublimation drying at -10°C to -5°C, and then subjected to desorption drying at 25°C to 30°C to obtain a lyophilized product of lornoxicam for injection.
5. The method for preparing the lyophilized product of lornoxicam for injection according to claim 4, wherein In S1, the preparation method of the lornoxicam liquid comprises the following steps: Add 75% to 85% of the prescription amount of water for injection, disodium edetate, tromethamine, lornoxicam, mannitol and a protective agent to the preparation tank in sequence, mix evenly, add water for injection to the total amount of preparation, filter, and obtain the lornoxicam liquid.
6. The method for preparing the lyophilized product of lornoxicam for injection according to claim 4 or 5, wherein: In S1, the pH of the lornoxicam solution is 8.5-9.
7. The method for preparing the lyophilized product of lornoxicam for injection according to claim 4, wherein: In S1, the temperature was programmed to drop to -25°C~-20°C, with a cooling rate of 0.5°C / min~1°C / min; In S1, the pre-freezing time is 30 min to 50 min.
8. The method for preparing the lyophilized product of lornoxicam for injection according to claim 4, wherein: In S1, the temperature was programmed to drop to -55°C~-50°C, with a cooling rate of 0.5°C / min~1°C / min; In S1, the freezing time is 30 min to 60 min.
9. The method for preparing the lyophilized product of lornoxicam for injection according to claim 4, wherein: In S2, the temperature was raised to -10°C~-5°C by programmed heating, with a heating rate of 1°C / min~2°C / min; In S2, the sublimation drying time is 2h~3h.
10. The method for preparing the lyophilized product of lornoxicam for injection according to claim 4, wherein: In S2, the temperature was raised to 25°C~30°C by programmed heating at a rate of 1°C / min~2°C / min; In S2, the time of the analytical drying is 1 h to 2 h.