Preparation method of oxytetracycline injection
By adding specific components to the oleracin injection and adopting improved preparation methods, the problems of oleracin injection are easily discolored, precipitated and reduced titer during storage, and the long-term stability and high titer maintenance of the injection are achieved.
Patent Information
- Application Number
- CN202411788165.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-06
- Publication Date
- 2025-03-11
AI Technical Summary
Otachomycin injection is prone to discoloration, precipitation and reduced titer during storage, especially when heated or stored for a long time under acidic or alkaline conditions.
By preparing an injection solution containing components such as oleracin base, homemade modified potassium sodium salicylate mixture, chlorphenamine maleate, recrystallized high-purity taurine, bupivacaine hydrochloride, modified soy lecithin and N,N-dimethylacetamide, specific formulas and preparation methods are used to improve stability.
This method significantly extends the storage time of oleracin injection, prevents discoloration and precipitation, improves stability, and maintains high titer for a long time.
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Figure CN119587556A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of medicine, and particularly relates to a method for preparing oxytetracycline injection. Background Art
[0002] Oxytetracycline ( O xytetracyc li ne ) is a broad-spectrum antibiotic synthesized by Streptomyces chelidonus through fermentation. Its structural formula is as shown in the attached Figure 3 As shown, it belongs to the tetracycline class. Oxytetracycline is the most widely used antibiotic in livestock and poultry and is a basic medicine for livestock and poultry health care. It is mainly used to treat respiratory tract, urinary tract and gastrointestinal tract infections caused by various bacteria, chlamydia, mycoplasma, etc. in animals. It can also be used for three-shot health care of young livestock.
[0003] Oxytetracycline is slightly soluble in water, soluble in methanol, ethanol, and propanedione; it is relatively stable in the air, but its color tends to darken when exposed to light. However, its preparations tend to darken in color, precipitate, and decrease in potency when exposed to heat or left for a long time, whether in acidic or alkaline conditions. This is because its aqueous solution decomposes through cross-isomerization, dehydration, hydrolysis, and oxidation reactions. Under acidic conditions, the hydroxyl group on C6 and the hydrogen on C5 undergo a trans-elimination reaction to form an orange-yellow dehydrate, while under alkaline conditions, an isomer with a lactone structure is formed, which becomes dark or black. Summary of the invention
[0004] The purpose of the present invention is to provide an oxytetracycline injection. Another purpose of the present invention is to provide an improved formula and preparation method of the above-mentioned veterinary oxytetracycline injection. Compared with other high-content veterinary oxytetracycline injections on the market, the improved formula and preparation method of the veterinary oxytetracycline injection have the characteristics of long storage time, not easy to change color, no precipitation and high stability.
[0005] In order to solve the above technical problems, the present invention provides an oxytetracycline injection, characterized in that each 100 ml of the injection includes the following components: oxytetracycline base 10-20 g, homemade modified potassium sodium salicylate mixture 1-2 g, chlorpheniramine maleate 2-3 g, recrystallized high-purity taurine 0.2-0.4 g, bupivacaine hydrochloride 4-5 g, modified soybean lecithin 25-30 g, N, -dimethylacetamide 20-30 g, ethanolamine 1.5-2.0 g, and the balance is water for injection.
[0006] Preferably, the preparation method of the homemade modified sodium potassium salicylate mixture is: adding salicylic acid to water with a volume 5 times its mass under stirring, adding a 5 mol / L sodium hydroxide aqueous solution with a molar amount of 0.6 times the salicylic acid dropwise, stirring for 20 minutes, adding a 5 mol / L potassium hydroxide aqueous solution with a molar amount of 0.4 times the salicylic acid dropwise, stirring for 30 minutes, concentrating under reduced pressure at 60°C until solid precipitates, adding ethanol with a volume 5 times the mass of salicylic acid, and continuing to concentrate under reduced pressure until the weight of the residue is 3 times the weight of salicylic acid, adding ethanol with a volume 5 times the mass of salicylic acid, and continuing to concentrate under reduced pressure until the weight of the residue is 2 times the weight of salicylic acid, cooling to 10 degrees Celsius, filtering, and drying under vacuum at 50°C to constant weight.
[0007] Preferably, the method for preparing recrystallized high-purity taurine is as follows: adding excess taurine to a 60°C aqueous solution, stirring for 30 minutes and filtering while hot, heating the filtrate to 60°C for redissolution, adding activated carbon 0.04 times the weight of the dissolved taurine, and continuing to heat and stir at 60°C for 30 minutes, filtering while hot, adding acetone in an equal volume of water to the filtrate under stirring, cooling to 5°C, stirring for 3 hours, recrystallizing, filtering, and drying in vacuo at 60°C to constant weight.
[0008] Preferably, the preparation method of the modified soybean lecithin is as follows: under argon protection, soybean lecithin is added to ethanol with a volume 5 times its volume, and osmium tetroxide with a molar amount of 2 times the molar amount of soybean lecithin and pyridine with a molar amount of 4 times the molar amount of soybean lecithin are added under stirring, heated to 45°C for reaction for 4 hours, cooled to 10°C, and a 5 mol / L aqueous solution containing sodium bisulfite with a molar amount of 1.5 times the molar amount of soybean lecithin is added dropwise, stirred at room temperature for 2 hours, filtered, evaporated under reduced pressure to obtain an oily substance, and subjected to column chromatography on a silica gel column with a weight 5 times that of the oily substance, the eluent being cyclohexane / ethyl acetate = 5 / 1, and the pure product is collected and evaporated under reduced pressure at 45°C to obtain the obtained product.
[0009] Preferably, the oxytetracycline base is pharmaceutical grade oxytetracycline base pure powder;
[0010] The chlorpheniramine maleate is pharmaceutical grade chlorpheniramine maleate pure powder;
[0011] The bupivacaine hydrochloride is a pharmaceutical grade bupivacaine hydrochloride pure powder;
[0012] The N,N-dimethylacetamide is pharmaceutical grade N,N-dimethylacetamide;
[0013] The ethanolamine is pharmaceutical grade ethanolamine.
[0014] A method for preparing oxytetracycline injection comprises the following steps:
[0015] S1. Under the protection of light-shielding argon, add oxytetracycline base and chlorpheniramine maleate into a reaction bottle, add N,N-dimethylacetamide and ethanolamine, ventilate, stir, heat and dissolve to obtain solution 1;
[0016] S2, adding modified soybean lecithin to solution 1 while stirring, and stirring to make it evenly dispersed to obtain solution 2;
[0017] S3, under argon protection, add a mixture of recrystallized high-purity taurine, bupivacaine hydrochloride and homemade modified potassium sodium salicylate to a reaction bottle, add water to ventilate, heat and stir to dissolve, and obtain solution 3;
[0018] S4. Add 2 drops of solution 3 into solution 3 under vigorous stirring, mix well, filter, fill with nitrogen and sterilize.
[0019] Preferably, the filtering method is a three-stage filtration, which includes a 1-micron titanium rod, a 0.45-micron filter element, and a 0.22-micron filter element.
[0020] Preferably, the sterilization method is flowing steam sterilization at 100°C for 15-30 minutes.
[0021] The beneficial effects of the present invention are:
[0022] 1. The homemade modified potassium sodium salicylate mixture provided by the present invention has the antipyretic, analgesic and antiseptic effects of sodium salicylate, the antiviral effect of potassium salicylate, and the anti-inflammatory effect of salicylic acid.
[0023] 2. The modified soybean lecithin provided by the present invention has a higher hydrophilicity than before the modification due to the addition of hydroxyl groups, and the suspension formed after mixing with water is more stable.
[0024] 3. The present invention adds taurine, which can relax the muscle contraction caused by the initial injection pain, and also has the effects of anti-oxidation, promoting immunity and promoting the absorption of lecithin-encapsulated drugs.
[0025] 4. The present invention adds bupivacaine hydrochloride, which has a local anesthetic effect, can reduce the discomfort caused by pain after injection, and reduce the infection caused by animal licking. BRIEF DESCRIPTION OF THE DRAWINGS
[0026] Figure 1 Schematic diagram of the corresponding chemical reaction of modified soybean lecithin.
[0027] Figure 2 Schematic diagram of the chemical reaction of homemade modified potassium sodium salicylate mixture.
[0028] Figure 3 The chemical structure of oxytetracycline. DETAILED DESCRIPTION
[0029] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the drawings of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. 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.
[0030] Embodiment 1:
[0031] Preparation of homemade modified potassium sodium salicylate mixture:
[0032] Salicylic acid is added to water in a volume 5 times its mass under stirring, and a 5 mol / L sodium hydroxide aqueous solution with a molar amount of 0.6 times the salicylic acid is added dropwise. After stirring for 20 minutes, a 5 mol / L potassium hydroxide aqueous solution with a molar amount of 0.4 times the salicylic acid is added dropwise. After stirring for 30 minutes, the mixture is concentrated under reduced pressure at 60°C until solid precipitates. Ethanol with a volume 5 times the mass of the salicylic acid is added and the mixture is concentrated under reduced pressure until the weight of the residue is 3 times the weight of the salicylic acid. Ethanol with a volume 5 times the mass of the salicylic acid is added and the mixture is concentrated under reduced pressure until the weight of the residue is 2 times the weight of the salicylic acid. The mixture is cooled to 10 degrees Celsius, filtered, and dried under vacuum at 50°C to constant weight.
[0033] Preparation of high purity taurine by recrystallization:
[0034] Add excess taurine to a 60°C aqueous solution, stir for 30 minutes and filter while hot. Heat the filtrate to 60°C for redissolution, add activated carbon 0.04 times the weight of dissolved taurine, continue heating and stirring at 60°C for 30 minutes, filter while hot, add acetone in an equal volume of water to the filtrate with stirring, cool to 5°C, stir and recrystallize for 3 hours, filter, and dry in a vacuum at 60°C to constant weight.
[0035] Preparation of modified soybean lecithin:
[0036] Under argon protection, soybean lecithin is added to ethanol with a volume 5 times its volume, and osmium tetroxide with a molar amount of 2 times the molar amount of soybean lecithin and pyridine with a molar amount of 4 times the molar amount of soybean lecithin are added under stirring, heated to 45°C for 4h, cooled to 10°C, and a 5 mol / L aqueous solution containing sodium bisulfite with a molar amount of 1.5 times the molar amount of soybean lecithin is added dropwise, stirred at room temperature for 2h, filtered, evaporated to dryness under reduced pressure to obtain an oily substance, and subjected to column chromatography on a silica gel column with a weight 5 times that of the oily substance, the eluent being cyclohexane / ethyl acetate = 5 / 1, and the pure product is collected and evaporated to dryness at 45°C under reduced pressure to obtain the obtained product.
[0037] The preparation process of the oxytetracycline injection is as follows:
[0038] (1) Under the protection of light-shielding argon, 50 g of oxytetracycline base and 10 g of chlorpheniramine maleate were added to a reaction bottle, and 100 g of N,N-dimethylacetamide and 7.5 g of ethanolamine were added. After ventilation, the mixture was stirred and heated to dissolve to obtain a solution 1;
[0039] (2) 125 g of modified soybean lecithin was added to solution 1 while stirring, and the mixture was stirred to be evenly dispersed to obtain solution 2;
[0040] (3) Under argon protection, 1 g of recrystallized high-purity taurine, 20 g of bupivacaine hydrochloride and 5 g of homemade modified potassium sodium salicylate were added to a reaction bottle, and 280 g of water for injection was added, and then heated and stirred to dissolve after ventilation to obtain Solution 3;
[0041] (4) Add 2 drops of solution 3 into solution 3 under vigorous stirring, mix well, filter, and fill with nitrogen to sterilize.
[0042] Embodiment 2:
[0043] Preparation of homemade modified potassium sodium salicylate mixture:
[0044] Salicylic acid is added to water in a volume 5 times its mass under stirring, and a 5 mol / L sodium hydroxide aqueous solution with a molar amount of 0.6 times the salicylic acid is added dropwise. After stirring for 20 minutes, a 5 mol / L potassium hydroxide aqueous solution with a molar amount of 0.4 times the salicylic acid is added dropwise. After stirring for 30 minutes, the mixture is concentrated under reduced pressure at 60°C until solid precipitates. Ethanol with a volume 5 times the mass of the salicylic acid is added and the mixture is concentrated under reduced pressure until the weight of the residue is 3 times the weight of the salicylic acid. Ethanol with a volume 5 times the mass of the salicylic acid is added and the mixture is concentrated under reduced pressure until the weight of the residue is 2 times the weight of the salicylic acid. The mixture is cooled to 10 degrees Celsius, filtered, and dried under vacuum at 50°C to constant weight.
[0045] Preparation of high purity taurine by recrystallization:
[0046] Add excess taurine to a 60°C aqueous solution, stir for 30 minutes and filter while hot. Heat the filtrate to 60°C for redissolution, add activated carbon 0.04 times the weight of dissolved taurine, continue heating and stirring at 60°C for 30 minutes, filter while hot, add acetone in an equal volume of water to the filtrate with stirring, cool to 5°C, stir and recrystallize for 3 hours, filter, and dry in a vacuum at 60°C to constant weight.
[0047] Preparation of modified soybean lecithin:
[0048] Under argon protection, soybean lecithin is added to ethanol with a volume 5 times its volume, and osmium tetroxide with a molar amount of 2 times the molar amount of soybean lecithin and pyridine with a molar amount of 4 times the molar amount of soybean lecithin are added under stirring, heated to 45°C for 4h, cooled to 10°C, and a 5 mol / L aqueous solution containing sodium bisulfite with a molar amount of 1.5 times the molar amount of soybean lecithin is added dropwise, stirred at room temperature for 2h, filtered, evaporated to dryness under reduced pressure to obtain an oily substance, and subjected to column chromatography on a silica gel column with a weight 5 times that of the oily substance, the eluent being cyclohexane / ethyl acetate = 5 / 1, and the pure product is collected and evaporated to dryness at 45°C under reduced pressure to obtain the obtained product.
[0049] The preparation process of the oxytetracycline injection is as follows:
[0050] (1) Under the protection of light-shielding argon, 75 g of oxytetracycline base and 12.5 g of chlorpheniramine maleate were added to a reaction bottle, and 125 g of N,N-dimethylacetamide and 9 g of ethanolamine were added. After ventilation, stirring and heating were performed to dissolve to obtain Solution 1;
[0051] (2) 135 g of modified soybean lecithin was added to solution 1 while stirring, and the mixture was stirred to be evenly dispersed to obtain solution 2;
[0052] (3) Under argon protection, 1.5 g of recrystallized high-purity taurine, 22.5 g of bupivacaine hydrochloride and 7.5 g of homemade modified potassium sodium salicylate were added to a reaction bottle, and 240 g of water for injection was added, and then heated and stirred to dissolve after ventilation to obtain Solution 3;
[0053] (4) Add 2 drops of solution 3 into solution 3 under vigorous stirring, mix well, filter, and fill with nitrogen to sterilize.
[0054] Embodiment 3:
[0055] Preparation of homemade modified potassium sodium salicylate mixture:
[0056] Salicylic acid is added to water in a volume 5 times its mass under stirring, and a 5 mol / L sodium hydroxide aqueous solution with a molar amount of 0.6 times the salicylic acid is added dropwise. After stirring for 20 minutes, a 5 mol / L potassium hydroxide aqueous solution with a molar amount of 0.4 times the salicylic acid is added dropwise. After stirring for 30 minutes, the mixture is concentrated under reduced pressure at 60°C until solid precipitates. Ethanol with a volume 5 times the mass of the salicylic acid is added and the mixture is concentrated under reduced pressure until the weight of the residue is 3 times the weight of the salicylic acid. Ethanol with a volume 5 times the mass of the salicylic acid is added and the mixture is concentrated under reduced pressure until the weight of the residue is 2 times the weight of the salicylic acid. The mixture is cooled to 10 degrees Celsius, filtered, and dried under vacuum at 50°C to constant weight.
[0057] Preparation of high purity taurine by recrystallization:
[0058] Add excess taurine to a 60°C aqueous solution, stir for 30 minutes and filter while hot. Heat the filtrate to 60°C for redissolution, add activated carbon 0.04 times the weight of dissolved taurine, continue heating and stirring at 60°C for 30 minutes, filter while hot, add acetone in an equal volume of water to the filtrate with stirring, cool to 5°C, stir and recrystallize for 3 hours, filter, and dry in a vacuum at 60°C to constant weight.
[0059] Preparation of modified soybean lecithin:
[0060] Under argon protection, soybean lecithin is added to ethanol with a volume 5 times its volume, and osmium tetroxide with a molar amount of 2 times the molar amount of soybean lecithin and pyridine with a molar amount of 4 times the molar amount of soybean lecithin are added under stirring, heated to 45°C for 4h, cooled to 10°C, and a 5 mol / L aqueous solution containing sodium bisulfite with a molar amount of 1.5 times the molar amount of soybean lecithin is added dropwise, stirred at room temperature for 2h, filtered, evaporated to dryness under reduced pressure to obtain an oily substance, and subjected to column chromatography on a silica gel column with a weight 5 times that of the oily substance, the eluent being cyclohexane / ethyl acetate = 5 / 1, and the pure product is collected and evaporated to dryness at 45°C under reduced pressure to obtain the obtained product.
[0061] The preparation process of the oxytetracycline injection is as follows:
[0062] (1) Under the protection of light-shielding argon, 100 g of oxytetracycline base and 15 g of chlorpheniramine maleate were added to a reaction bottle, and 150 g of N,N-dimethylacetamide and 10 g of ethanolamine were added. After ventilation, the mixture was stirred and heated to dissolve to obtain a solution 1;
[0063] (2) 150 g of modified soybean lecithin was added to solution 1 while stirring, and the mixture was stirred to be evenly dispersed to obtain solution 2;
[0064] (3) Under argon protection, 2 g of recrystallized high-purity taurine, 25 g of bupivacaine hydrochloride and 10 g of homemade modified potassium sodium salicylate were added to a reaction bottle, and 200 g of water for injection was added, and the mixture was heated and stirred to dissolve after ventilation to obtain Solution 3;
[0065] (4) Add 2 drops of solution 3 into solution 3 under vigorous stirring, mix well, filter, and fill with nitrogen to sterilize.
[0066] Comparative Example 1:
[0067] Same as Example 1, except that the modified soybean lecithin is replaced by soybean lecithin.
[0068] Comparative Example 2:
[0069] Same as Example 1, except that bupivacaine hydrochloride was not added.
[0070] Drug stability experiment at room temperature: The oxytetracycline injection obtained in Example 1-3 and Comparative Example 1-2 was sealed and packaged in brown ampoules, placed at a temperature of 25±5°C and a relative humidity of 60% for 36 months, and its color was observed and the oxytetracycline content was detected.
[0071] Drug suspension stability experiment: The oxytetracycline injection obtained in Examples 1-3 and Comparative Examples 1-2 was sealed and packaged in brown ampoules, placed at a temperature of 25±5°C and a relative humidity of 60% for 36 months, and observed for any oil-water separation or stratification.
[0072] Drug high temperature stability experiment: The oxytetracycline injection obtained in Example 1-3 and Comparative Example 1-2 was sealed and packaged in brown ampoules, placed at a temperature of 40±5°C and a relative humidity of 60% for 6 months, and its color was observed and the oxytetracycline content was detected.
[0073] Drug light stability experiment: The oxytetracycline injection obtained in Example 1-3 and Comparative Example 1-2 was sealed and packaged in brown ampoules, and placed at a temperature of 25° C. and a light intensity of 5000 Lx for 15 days.
[0074] Animal reaction experiment after medication: The oxytetracycline injection obtained in Example 1-3 and Comparative Example 1-2 was injected into sick dogs, with 5 dogs in each group, and the licking of the injected dogs at the injection site was observed.
[0075] The test results are shown in the following table:
[0076]
[0077]
[0078] Test results: It can be seen from the results of Examples 1-3 and Comparative Examples 1-2 that the prepared modified soybean lecithin can make the suspension more stable, and the oxytetracycline encapsulated by the modified soybean lecithin can be preserved for a longer period of time; adding bupivacaine hydrochloride can reduce local discomfort after injection.
[0079] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.
Claims
1. A oxytetracycline injection, characterized in that: Each 100 ml injection contains the following components: Oxytetracycline base 10-20g, homemade modified potassium sodium salicylate mixture 1-2g, chlorpheniramine maleate 2-3g, recrystallized high-purity taurine 0.2-0.4g, bupivacaine hydrochloride 4-5g, modified soybean lecithin 25-30g, N,N-dimethylacetamide 20-30g, ethanolamine 1.5-2.0g, and the balance is water for injection.
2. The oxytetracycline injection according to claim 1, characterized in that: The preparation method of the homemade modified sodium potassium salicylate mixture is as follows: adding salicylic acid to water with a volume of 5 times the mass of salicylic acid under stirring, dripping a 5 mol / L sodium hydroxide aqueous solution with a molar amount of 0.6 times the mass of salicylic acid, dripping a 5 mol / L potassium hydroxide aqueous solution with a molar amount of 0.4 times the mass of salicylic acid, stirring for 20 minutes, concentrating under reduced pressure at 60° C. until solid precipitates, adding ethanol with a volume of 5 times the mass of salicylic acid, and continuing to concentrate under reduced pressure until the weight of the residue is 3 times the weight of salicylic acid, adding ethanol with a volume of 5 times the mass of salicylic acid, and continuing to concentrate under reduced pressure until the weight of the residue is 2 times the weight of salicylic acid, cooling to 10 degrees Celsius, filtering, and vacuum drying at 50° C. to obtain the mixture.
3. The oxytetracycline injection according to claim 1, characterized in that: The method for preparing recrystallized high-purity taurine is as follows: adding excess taurine to a 60° C. aqueous solution, stirring for 30 minutes and filtering while hot, heating the filtrate to 60° C. for redissolution, adding activated carbon 0.04 times the weight of the dissolved taurine, and continuing to heat and stir at 60° C. for 30 minutes, filtering while hot, adding acetone in an equal volume to the volume of water to the filtrate under stirring, cooling to 5° C., stirring for 3 hours, recrystallizing, filtering, and vacuum drying at 60° C. to obtain the taurine.
4. The oxytetracycline injection according to claim 1, characterized in that: The preparation method of the modified soybean lecithin is as follows: under argon protection, soybean lecithin is added to ethanol with a volume 5 times the volume of the soybean lecithin, osmium tetroxide with a molar amount 2 times the molar amount of soybean lecithin and pyridine with a molar amount 4 times the molar amount of soybean lecithin are added under stirring, heating to 45°C for reaction for 4 hours, cooling to 10°C, adding dropwise a 5 mol / L aqueous solution containing sodium bisulfite with a molar amount 1.5 times the molar amount of soybean lecithin, stirring at room temperature for 2 hours, filtering, evaporating under reduced pressure to obtain an oily substance, passing the oily substance through a silica gel column with a weight 5 times the weight of the oily substance for column chromatography, the eluent being cyclohexane / ethyl acetate = 5 / 1, collecting a pure product and evaporating under reduced pressure at 45°C to obtain the product.
5. The oxytetracycline injection according to claim 1, characterized in that: The oxytetracycline base is a pharmaceutical grade oxytetracycline base pure powder; The chlorpheniramine maleate is a pharmaceutical grade chlorpheniramine maleate pure powder; The bupivacaine hydrochloride is a pharmaceutical grade bupivacaine hydrochloride pure powder; The N,N-dimethylacetamide is pharmaceutical grade N,N-dimethylacetamide; The ethanolamine is pharmaceutical grade ethanolamine.
6. A method for preparing oxytetracycline injection according to any one of claims 1 to 5, characterized in that: The following steps are involved: S1. Under the protection of light-shielding argon, add oxytetracycline base and chlorpheniramine maleate into a reaction bottle, add N,N-dimethylacetamide and ethanolamine, ventilate, stir, heat and dissolve to obtain solution 1; S2, adding modified soybean lecithin to solution 1 while stirring, stirring to make it evenly dispersed to obtain solution 2; S3, under argon protection, add a mixture of recrystallized high-purity taurine, bupivacaine hydrochloride and homemade modified potassium sodium salicylate to a reaction bottle, add water to ventilate, heat and stir to dissolve, and obtain solution 3; S4. Add 2 drops of solution 3 into solution 3 under vigorous stirring, mix well, filter, fill with nitrogen and sterilize.
7. The method for preparing oxytetracycline injection according to claim 6, characterized in that: The filtering method is a three-stage filtration, which includes a 1-micron titanium rod, a 0.45-micron filter element, and a 0.22-micron filter element.
8. The method for preparing oxytetracycline injection according to claim 6, characterized in that: The sterilization method is 100° C. flowing steam sterilization for 15-30 minutes.
Citation Information
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