Oxytetracycline injection and preparation method thereof

Abstract

The invention discloses an oxytetracycline injection and a preparation method thereof, and the oxytetracycline injection is prepared from the following components in parts by weight: 18 to 22 parts of oxytetracycline, 35 to 50 parts of polyethylene glycol 400, 0.4 to 0.6 part of sodium formaldehyde sulfoxylate, 1.6 to 1.8 parts of magnesium oxide, 40 to 60 parts of acetamide, 0.5 to 1.5 parts of sodium formaldehyde sulfoxylate, 20 to 30 parts of oxytetracycline hydrochloride and 1.8 to 2.5 parts of magnesium oxide. The oxytetracycline is prepared by adding an oxytetracycline raw material into a methanol aqueous solution, dropwise adding hydrochloric acid to dissolve, adding modified activated carbon to remove impurities, filtering, dropwise adding ammonia water into the obtained filtrate, crystallizing, filtering and drying, and the oxytetracycline injection prepared by the preparation method disclosed by the invention is relatively high in product purity and relatively low in visible foreign matter content, and the amount of integrally used pyrrolidone is relatively small; the irritation is relatively low.

Description

TECHNICAL FIELD

[0001] The present application relates to oxytetracycline injection technical field, more specifically, it relates to a kind of oxytetracycline injection and preparation method thereof. BACKGROUND

[0002] Oxytetracycline injection is a kind of antibiotic drugs, its main component is oxytetracycline, belongs to tetracycline antibiotics.The main mechanism of action is by combining with bacterial ribosome 30S subunit, prevent aminoacyl-tRNA from entering A site, so as to inhibit the synthesis of bacterial protein, play antibacterial action.But the existing technology is to produce oxytetracycline by fermentation method, in the post-process of oxytetracycline produced by fermentation method, often through optimizing process conditions to improve product quality;But due to the fermentation process will produce a large amount of protein, metal ions and other organic byproducts and impurities, resulting in poor overall product purity, impurity content, poor stability of oxytetracycline injection prepared in later period and other problems. SUMMARY

[0003] (I) technical problem solved In view of the problems existing in the prior art, the present application provides a kind of oxytetracycline injection and preparation method thereof, to solve the technical problems mentioned in the background art.

[0004] (II) technical scheme To achieve the above object, the present application provides the following technical scheme: a kind of oxytetracycline injection, by weight parts, the formula of the oxytetracycline injection prepared includes: oxytetracycline 18-22 parts, polyethylene glycol 400 35-50 parts, formaldehyde sodium bisulfite 0.4-0.6 parts, magnesium oxide 1.6-1.8 parts, acetamide 40%-60 parts, white block 0.5-1.5 parts, oxytetracycline hydrochloride 20-30 parts and magnesium oxide 1.8-2.5 parts.

[0005] The present application is further provided that the oxytetracycline is to oxytetracycline raw material into methanol aqueous solution, after adding hydrochloric acid, adding modified activated carbon to remove impurities, filter, the obtained filtrate is added dropwise ammonia and crystallization, filter, dry, and obtain.

[0006] The present application is further provided that the purity of oxytetracycline hydrochloride is more than 95%.

[0007] The present application is further provided that the particle size of magnesium oxide is 10-15 microns.

[0008] The present application is further provided that the white block is a high-efficiency composite adsorbent.

[0009] The present application also includes a kind of oxytetracycline injection preparation method, characterized by: including the following steps: Step one: select acetamide 40%, 45%, 50%, 55%, 60% dosage for parallel experiment; Step two: terramycin injection is prepared by mixing N-methyl pyrrolidone and deionized water, then adding formaldehyde and sodium formaldehyde sulfoxylate, magnesium oxide, dispersing and heating, then adding terramycin raw material, and then heating for complexation reaction, adding monoethanolamine for the first time to adjust the pH value, using PS-20 membrane for ultrafiltration, adding monoethanolamine for the second time to adjust the pH value, and constant volume; Step three: add terramycin raw material, and then heat for complexation reaction, add monoethanolamine for the first time to adjust the pH value, use PS-20 membrane for ultrafiltration, add monoethanolamine for the second time to adjust the pH value, constant volume, filtration, and the terramycin injection is obtained. Step four: finally, the liquid medicine is sterilely filled.

[0010] The application further provides that the preparation process of the modified activated carbon is as follows: the activated carbon is treated with hydrogen peroxide to obtain oxidized activated carbon; zinc sulfate is dissolved in deionized water, and the oxidized activated carbon is added and ultrasonically treated, and then potassium ferrocyanide is added and continuously stirred, and then filtered, dried and calcined to obtain the modified activated carbon.

[0011] The application further provides that in the preparation process of the modified activated carbon, the weight ratio of the oxidized activated carbon, zinc sulfate and potassium ferrocyanide is 10:1.3-1.5:1.5-1.8.

[0012] The application further provides that the step two ring includes accelerated experimental treatment, and the method of the accelerated experiment is to accelerate the reaction system under high temperature and high humidity conditions.

[0013] The application further provides that the filtration mode is microporous membrane filtration.

[0014] (Three) beneficial effects Compared with the prior art, the application provides a terramycin injection and a preparation method thereof, which has the following beneficial effects: The application optimizes the components of the liquid medicine and precisely controls the preparation process, so that the terramycin injection releases stable and efficient drugs, has less irritation and better drug efficacy. At the same time, the preparation process of the terramycin injection provided by the application is simple, easy to operate, and can ensure the sterility and stability of the liquid medicine. In addition, the terramycin injection formula and preparation process provided by the application also have the advantages of low cost, short preparation period and strong adaptability, and therefore have a wide application prospect. In addition, the terramycin injection product prepared by the application has high purity, low visible foreign matter content, and low irritation due to small amount of pyrrolidone used. Specific implementation

[0015] It should be noted that the embodiments in the present application and the features in the embodiments can be combined with each other without conflict. The present application will be described in detail below in combination with the embodiments.

[0016] It should be noted that all the technical and scientific terms used in the present application have the same meaning as that generally understood by the ordinary skilled in the art to which the present application belongs, unless otherwise specified.

[0017] Embodiment 1: A terramycin injection, the formula for preparing the terramycin injection includes, by weight fraction, terramycin 18-22 parts, polyethylene glycol 400 35-50 parts, formaldehyde sodium bisulfite 0.4-0.6 parts, magnesium oxide 1.6-1.8 parts, acetamide 40%-60% parts, sodium sulfite 0.5-1.5 parts, terramycin hydrochloride 20-30 parts, and magnesium oxide 1.8-2.5 parts.

[0018] In a further embodiment, the terramycin is obtained by adding terramycin raw material to an aqueous methanol solution, adding hydrochloric acid dropwise to dissolve, adding modified activated carbon to remove impurities, filtering, adding ammonia water dropwise to the obtained filtrate and performing crystallization, filtering, and drying to obtain; the purity of the terramycin hydrochloride is more than 95%; the particle size of the magnesium oxide is 10-15 microns; and the sodium sulfite is a high-efficiency composite adsorbent.

[0019] Embodiment 2: Based on embodiment 1, the present application further includes a terramycin injection preparation method, characterized by comprising the following steps: Step one: preparing raw materials: terramycin 18 parts, polyethylene glycol 400 35 parts, formaldehyde sodium bisulfite 0.4 parts, magnesium oxide 1.6 parts, acetamide 40% parts, sodium sulfite 0.5 parts, terramycin hydrochloride 20 parts, and magnesium oxide 1.8 parts, and selecting acetamide 40%, 45%, 50%, 55%, and 60% dosage for parallel experiments; Step two: the terramycin injection is obtained by mixing N-methyl pyrrolidone and deionized water, then adding formaldehyde sodium bisulfite and magnesium oxide in sequence, dispersing and heating, then adding terramycin raw material, heating again for complexation reaction, adding monoethanolamine for the first time to adjust pH value, using PS-20 membrane for ultrafiltration of the obtained solution, adding monoethanolamine for the second time to adjust pH value, and constant volume; Step three: adding terramycin raw material, heating again for complexation reaction, adding monoethanolamine for the first time to adjust pH value, using PS-20 membrane for ultrafiltration of the obtained solution, adding monoethanolamine for the second time to adjust pH value, constant volume, and filtering to obtain the terramycin injection; Step four: finally, the drug solution is aseptically filled; the preparation process of the modified activated carbon is as follows: after the activated carbon is treated with hydrogen peroxide, the oxidized activated carbon is obtained; zinc sulfate is taken and dissolved in deionized water, the oxidized activated carbon is added, ultrasonic treatment is performed, then potassium ferrocyanide is added, continuous stirring is performed, filtration is performed, drying is performed, calcination is performed, and the modified activated carbon is prepared; in the preparation process of the modified activated carbon, the weight ratio among the oxidized activated carbon, zinc sulfate and potassium ferrocyanide is 10:1.3-1.5:1.5-1.8; the step two cycle includes accelerated experiment treatment, and the method of the accelerated experiment is to accelerate the reaction system under high temperature and high humidity conditions; and the filtration mode is micro-porous filter membrane filtration.

[0020] Example 3: On the basis of example 1, the application further includes a terramycin injection preparation method, characterized by comprising the following steps: Step one: preparing raw materials: terramycin 22 parts, polyethylene glycol 400 50 parts, formaldehyde sodium bisulfite 0.6 parts, magnesium oxide 1.8 parts, acetamide 60 parts, sodium chloride 1.5 parts, terramycin hydrochloride 30 parts and magnesium oxide 2.5 parts, and selecting acetamide 40%, 45%, 50%, 55%, 60% for parallel experiment; Step two: the terramycin injection is prepared by mixing N-methyl pyrrolidone and deionized water, then adding formaldehyde sodium bisulfite and magnesium oxide in sequence, dispersing and heating, then adding terramycin raw material, heating again for complexation reaction, adding monoethanolamine for the first time to adjust pH value, using PS-20 membrane for ultrafiltration of the obtained solution, adding monoethanolamine for the second time to adjust pH value of the obtained filtrate, and constant volume; Step three: adding terramycin raw material, heating again for complexation reaction, adding monoethanolamine for the first time to adjust pH value, using PS-20 membrane for ultrafiltration of the obtained solution, adding monoethanolamine for the second time to adjust pH value of the obtained filtrate, constant volume, filtration, and thus the terramycin injection is obtained; Step four: finally, the drug solution is aseptically filled; the preparation process of the modified activated carbon is as follows: after the activated carbon is treated with hydrogen peroxide, the oxidized activated carbon is obtained; zinc sulfate is taken and dissolved in deionized water, the oxidized activated carbon is added, ultrasonic treatment is performed, then potassium ferrocyanide is added, continuous stirring is performed, filtration is performed, drying is performed, calcination is performed, and the modified activated carbon is prepared; in the preparation process of the modified activated carbon, the weight ratio among the oxidized activated carbon, zinc sulfate and potassium ferrocyanide is 10:1.3-1.5:1.5-1.8; the step two cycle includes accelerated experiment treatment, and the method of the accelerated experiment is to accelerate the reaction system under high temperature and high humidity conditions; and the filtration mode is micro-porous filter membrane filtration.

[0021] While embodiments of the application have been shown and described, it is to be understood that the embodiments described are merely exemplary of the principles and application of the present application. Numerous modifications and adaptions can be effected without departing from the spirit and scope of the present application, which is not limited to the exact construction and arrangement described. It is intended, therefore, to cover all modifications and adaptions that fall within the scope of the claims and their equivalents.

Claims

1. An oxytetracycline injection solution, characterized in that, The formulation for the oxytetracycline injection, by weight, comprises: 18-22 parts oxytetracycline, 35-50 parts polyethylene glycol 400, 0.4-0.6 parts sodium formaldehyde sulfoxylate, 1.6-1.8 parts magnesium oxide, 40%-60 parts acetamide, 0.5-1.5 parts sodium formaldehyde sulfoxylate, 20-30 parts oxytetracycline hydrochloride, and 1.8-2.5 parts magnesium oxide.

2. The oxytetracycline injection solution according to claim 1, characterized in that: The oxytetracycline is prepared by adding oxytetracycline raw material to a methanol aqueous solution, dissolving it with hydrochloric acid, adding modified activated carbon to remove impurities, filtering, adding ammonia water to the filtrate and crystallizing, filtering, and drying.

3. The oxytetracycline injection solution according to claim 2, characterized in that: The purity of the oxytetracycline hydrochloride is above 95%.

4. The oxytetracycline injection solution according to claim 3, characterized in that: The magnesium oxide has a particle size of 10-15 micrometers.

5. The oxytetracycline injection solution according to claim 4, characterized in that: The sodium formaldehyde sulfoxylate is a highly efficient composite adsorbent.

6. The present invention also includes a method for preparing oxytetracycline injection, characterized in that: Includes the following steps: Step 1: Prepare raw materials and conduct parallel experiments using acetamide at concentrations of 40%, 45%, 50%, 55%, and 60%. Step 2: Oxytetracycline injection is prepared by mixing N-methylpyrrolidone and deionized water, then adding sodium formaldehyde sulfoxylate and magnesium oxide in sequence, dispersing and heating, then adding oxytetracycline raw material, heating again to carry out complexation reaction, adding monoethanolamine to adjust the pH value for the first time, and ultrafiltration of the resulting solution using a PS-20 membrane, adding monoethanolamine to the filtrate for the second time to adjust the pH value, and then making up to volume. Step 3: Add oxytetracycline raw material, then heat to carry out complexation reaction. Add monoethanolamine for the first time to adjust the pH value. Use a PS-20 membrane to ultrafilter the resulting solution. Add monoethanolamine for the second time to adjust the pH value of the filtrate, make up to volume, and filter to obtain the oxytetracycline injection solution. Step 4: Finally, the medicine solution is aseptically filled.

7. The method for preparing oxytetracycline injection according to claim 6, characterized in that: The preparation process of the modified activated carbon is as follows: activated carbon is treated with hydrogen peroxide to obtain oxidized activated carbon; zinc sulfate is dissolved in deionized water, the oxidized activated carbon is added, ultrasonic treatment is performed, potassium ferrocyanide is added, and the mixture is continuously stirred, filtered, dried, and calcined to obtain the modified activated carbon.

8. The method for preparing oxytetracycline injection according to claim 6, characterized in that: In the preparation of modified activated carbon, the weight ratio of oxidized activated carbon to zinc sulfate and potassium ferrocyanide is 10:1.3-1.5:1.5-1.

8.

9. The method for preparing oxytetracycline injection according to claim 6, characterized in that: The second step includes accelerated experimental treatment, which involves using high temperature and high humidity conditions to accelerate the reaction system.

10. The method for preparing oxytetracycline injection according to claim 6, characterized in that: The filtration method is microporous membrane filtration.