CN107261108B - Long-acting amoxicillin and colistin sulfate injection and preparation method thereof - Google Patents
Long-acting amoxicillin and colistin sulfate injection and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a long-acting amoxicillin and colistin sulfate injection and a preparation method thereof, wherein the injection comprises the following components in parts by weight: 8-12 parts of amoxicillin, 0.2-0.9 part of colistin sulfate, 1-3 parts of suspending agent, 0.5-1.5 parts of wetting agent, 0.3-0.8 part of antioxidant, 0.2-0.5 part of zinc oxide, 0.8-1.5 parts of clavulanic acid, 1.2-2.5 parts of pH stabilizer and 80-150 parts of dispersion medium; the preparation method comprises adding suspending agent, wetting agent, antioxidant, zinc oxide, clavulanic acid and pH stabilizer into dispersion medium, adding amoxicillin and colistin sulfate, and grinding. Compared with the prior art, the invention not only can increase the drug effect while reducing the dosage of the components, but also can prolong the metabolism time of the drug effect, can achieve the same effect of multiple interval injections of the same variety of conventional dosage forms by one injection, reduces the drug administration times, reduces the drug administration cost and the labor cost, avoids the occurrence of stress reaction, improves the suspension adhesion effect of the effective bactericidal components, and has good dispersibility.
Description
Technical Field
The invention belongs to the technical field of animal medicines, and relates to a long-acting amoxicillin and colistin sulfate injection and a preparation method thereof.
Background
In the process of animal breeding, various antibiotics are often needed for the rapid treatment of diseased animals. The amoxicillin is a semi-synthetic broad-spectrum antibiotic, has strong antibacterial action on most gram-positive bacteria and gram-negative bacteria, and is combined with Penicillin Binding Protein (PBP) on a bacterial cell membrane to prevent synthesis of bacterial cell wall mucopeptide, so that the bacterial cell wall mucopeptide cannot be crosslinked to cause cell wall defect, and bacterial cells are ruptured and dead, thereby achieving the aim of healing.
Amoxicillin as a beta-lactam antibiotic has strong antibacterial activity, broad antibacterial spectrum and low drug resistance, but has short half-life period, needs frequent administration, and can generate larger stimulation to organisms by continuous intramuscular injection. In addition, the amoxicillin is unstable in chemical property, and the beta-lactam ring in the structure of the amoxicillin is easy to hydrolyze under the condition of strong acid or strong alkali, so that the clinical application of the amoxicillin is greatly limited. In practical application, amoxicillin and colistin sulfate are often compounded to prepare an amoxicillin colistin sulfate injection. Wherein the colistin sulfate is a polypeptide antibiotic, has strong antibacterial effect on gram-negative bacteria, and sensitive bacteria comprise Escherichia coli, salmonella, Shigella, Pasteurella and the like. The two medicines are combined to act synergistically or additively on main pathogenic bacteria such as actinobacillus pleuropneumoniae, escherichia coli and the like. However, the existing amoxicillin and colistin sulfate injection has the main disadvantages that the amoxicillin and colistin sulfate injection is not easy to store for a long time, has short action time, can achieve a continuous sterilization effect only by continuous injection for a plurality of days, not only increases the breeding cost of a farm, but also easily causes the stress reaction of animals.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a long-acting amoxicillin and colistin sulfate injection which is easy to store and has long drug effect time and a preparation method thereof.
The purpose of the invention can be realized by the following technical scheme:
the long-acting amoxicillin and colistin sulfate injection comprises the following components in parts by weight: 8-12 parts of amoxicillin, 0.2-0.9 part of colistin sulfate, 1-3 parts of suspending agent, 0.5-1.5 parts of wetting agent, 0.3-0.8 part of antioxidant, 0.2-0.5 part of zinc oxide, 0.8-1.5 parts of clavulanic acid, 1.2-2.5 parts of pH stabilizer and 80-150 parts of dispersion medium.
As a preferable technical scheme, the injection comprises the following components in parts by weight: 9-11 parts of amoxicillin, 0.5-0.7 part of colistin sulfate, 1.5-2.5 parts of suspending agent, 0.8-1.2 parts of wetting agent, 0.4-0.7 part of antioxidant, 0.3-0.4 part of zinc oxide, 1-1.2 parts of clavulanic acid, 1.7-2.2 parts of pH stabilizer and 120 parts of dispersion medium 100-.
As a further preferable technical scheme, the injection comprises the following components in parts by weight: 10 parts of amoxicillin, 0.6 part of colistin sulfate, 2 parts of suspending agent, 1 part of wetting agent, 0.5 part of antioxidant, 0.35 part of zinc oxide, 1.1 part of clavulanic acid, 2 parts of pH stabilizer and 110 parts of dispersion medium.
The suspending agent is a mixture of aluminum monostearate and cholesterol, and the mass ratio of the aluminum monostearate to the cholesterol in the suspending agent is 3-5: 1.
The wetting agent is hydrogenated castor oil.
The antioxidant is vitamin E or sodium formaldehyde sulfoxylate.
The preparation method of the pH stabilizer comprises the following steps: mixing potassium dihydrogen phosphate with a sodium hydroxide solution, and adding water to dilute the mixture, wherein the molar concentration of the sodium hydroxide solution is 0.05-0.15mol/L, and 0.6-0.7g of potassium dihydrogen phosphate and 12-18mL of the sodium hydroxide solution are added in each 100mL of water.
The dispersion medium comprises soybean oil, benzyl benzoate and diacetin, and the mass ratio of the soybean oil to the benzyl benzoate to the diacetin is 1:0.5-1: 0.5-1. Wherein the soybean oil is soybean oil for injection.
A preparation method of a long-acting amoxicillin and colistin sulfate injection comprises the following steps:
1) respectively adding a suspending agent, a wetting agent, an antioxidant, zinc oxide, clavulanic acid and a pH stabilizer into a dispersion medium, and uniformly stirring to obtain a dispersion liquid;
2) adding the dispersion into a colloid mill, and starting the colloid mill;
3) and respectively adding amoxicillin and colistin sulfate into a colloid mill to obtain a suspension, and grinding to obtain the long-acting amoxicillin and colistin sulfate injection.
The prepared injection is convenient to store and transport after filling, sealing and sterilizing.
In the step 1), the stirring temperature is 80-90 ℃. Dispersion is promoted by raising the temperature.
In the step 3), the fineness of the particles in the suspension is 5-15 μm. During grinding, the mode of alternating cyclic grinding and non-cyclic grinding can be adopted, the particle fineness is controlled to be 5-15 mu m, the fluidity of the suspension is improved, the problem of wall hanging of the suspension is avoided, and the needle penetration is greatly improved.
The injection can be used for treating animal diseases.
According to the invention, amoxicillin and colistin sulfate are used as effective sterilization components, and the antibacterial effects of the two components are mutually superposed, so that germs can be quickly killed, and the physical ability of animals can be recovered; the suspending agent can improve the suspending effect and the stability of an injection system, increase the viscosity of a dispersing medium, slow down the sedimentation speed of particles, and can be adsorbed on the surfaces of the particles to form a barrier for preventing the aggregation and agglomeration of the particles; the wetting agent can uniformly disperse all components, so that the dispersion degree of a dispersed phase is large, the stability is good, and the adverse effect of external factors is reduced; the antioxidant can further improve the stability of the injection and avoid oxidative denaturation; the dispersion medium is used as a solvent of the injection, and the benzyl benzoate in the dispersion medium not only can play a role of the solvent, but also has certain slow release performance, can increase the curative effect and effective action time of the injection, and prolongs the medicinal effect of the injection in animals.
The beta-lactamase produced by the bacteria can lead amoxicillin to be hydrolyzed and inactivated, thus causing the bacteria to generate drug resistance. The clavulanic acid is a broad-spectrum beta-lactamase inhibitor, has only weak antibacterial activity, but has strong inhibition effect on various beta-lactamase, can be firmly combined with most beta-lactamase to generate an irreversible combination, thereby preventing enzyme-intolerant amoxicillin from being damaged by enzyme, enhancing the antibacterial activity and expanding the antibacterial spectrum. By adding clavulanic acid into the injection, the dosage of amoxicillin can be greatly reduced, the antibacterial spectrum of amoxicillin is widened, the antibacterial activity is enhanced, and the injection has obvious synergistic effect on various bacteria producing beta-lactamase, such as staphylococcus aureus, escherichia coli, pneumonia bacillus, proteus mirabilis, ordinary proteus, flu bacillus, fragile bacillus and the like.
The colistin sulfate has certain toxicity, and the dosage of the colistin sulfate can be reduced while the sterilization effect is ensured by adding the zinc oxide into the injection.
Because the chemical property of amoxicillin is unstable, the beta-lactam ring in the structure is easy to hydrolyze under the condition of strong acid or strong alkali, and the colistin sulfate is sensitive to the change of pH, the pH stabilizer is added into the injection to control the pH value of the injection to be between 6 and 7, so that the storage time of the injection can be prolonged.
Compared with the prior art, the invention has the following characteristics:
1) through the mutual matching of the components in the injection, the drug effect can be increased while the dosage of the components is reduced, the drug effect metabolism time can be prolonged, the same effect of multiple interval injections of the same variety of conventional dosage forms can be achieved by one-time injection, the drug administration times are reduced, the drug administration cost and the labor cost are reduced, and the stress reaction is avoided;
2) when the injection is prepared, the suspending agent, the wetting agent, the antioxidant, the zinc oxide, the clavulanic acid and the pH stabilizer are added into the dispersion medium, and then the amoxicillin and the colistin sulfate are added, so that the bearing capacity of the effective sterilization component is increased, the suspension adhesion effect of the effective sterilization component is improved, and the dispersibility is good.
Detailed Description
The present invention will be described in detail with reference to specific examples. The present embodiment is implemented on the premise of the technical solution of the present invention, and a detailed implementation manner and a specific operation process are given, but the scope of the present invention is not limited to the following embodiments.
Example 1:
the long-acting amoxicillin and colistin sulfate injection comprises the following components in parts by weight: 8 parts of amoxicillin, 0.9 part of colistin sulfate, 1 part of suspending agent, 1.5 parts of wetting agent, 0.3 part of antioxidant, 0.5 part of zinc oxide, 0.8 part of clavulanic acid, 2.5 parts of pH stabilizer and 80 parts of dispersion medium.
Wherein the suspending agent is a mixture of aluminum monostearate and cholesterol, and the mass ratio of the aluminum monostearate to the cholesterol in the suspending agent is 4.5: 1; the wetting agent is hydrogenated castor oil; the antioxidant is vitamin E; the preparation method of the pH stabilizer comprises the following steps: mixing potassium dihydrogen phosphate with a sodium hydroxide solution, and adding water for dilution, wherein the molar concentration of the sodium hydroxide solution is 0.05mol/L, and 0.7g of potassium dihydrogen phosphate and 12mL of the sodium hydroxide solution are added in each 100mL of water; the dispersion medium comprises soybean oil, benzyl benzoate and diacetin, and the mass ratio of the soybean oil to the benzyl benzoate to the diacetin is 1:1: 0.5.
A preparation method of a long-acting amoxicillin and colistin sulfate injection comprises the following steps:
1) respectively adding a suspending agent, a wetting agent, an antioxidant, zinc oxide, clavulanic acid and a pH stabilizer into a dispersion medium, and uniformly stirring to obtain a dispersion liquid;
2) adding the dispersion into a colloid mill, and starting the colloid mill;
3) adding amoxicillin and colistin sulfate into a colloid mill respectively to obtain a suspension, and grinding the suspension until the particle fineness is 5-15 mu m to obtain the long-acting amoxicillin and colistin sulfate injection.
Example 2:
the long-acting amoxicillin and colistin sulfate injection comprises the following components in parts by weight: 12 parts of amoxicillin, 0.2 part of colistin sulfate, 3 parts of suspending agent, 0.5 part of wetting agent, 0.8 part of antioxidant, 0.2 part of zinc oxide, 1.5 parts of clavulanic acid, 1.2 parts of pH stabilizer and 150 parts of dispersion medium.
Wherein the suspending agent is a mixture of aluminum monostearate and cholesterol, and the mass ratio of the aluminum monostearate to the cholesterol in the suspending agent is 3.5: 1; the wetting agent is hydrogenated castor oil; the antioxidant is sodium formaldehyde sulfoxylate; the preparation method of the pH stabilizer comprises the following steps: mixing potassium dihydrogen phosphate with a sodium hydroxide solution, and adding water for dilution, wherein the molar concentration of the sodium hydroxide solution is 0.15mol/L, and 0.6g of potassium dihydrogen phosphate and 18mL of the sodium hydroxide solution are added in every 100mL of water; the dispersion medium comprises soybean oil, benzyl benzoate and diacetin, and the mass ratio of the soybean oil to the benzyl benzoate to the diacetin is 1:0.5: 1.
A preparation method of a long-acting amoxicillin and colistin sulfate injection comprises the following steps:
1) respectively adding a suspending agent, a wetting agent, an antioxidant, zinc oxide, clavulanic acid and a pH stabilizer into a dispersion medium, and uniformly stirring to obtain a dispersion liquid;
2) adding the dispersion into a colloid mill, and starting the colloid mill;
3) adding amoxicillin and colistin sulfate into a colloid mill respectively to obtain a suspension, and grinding the suspension until the particle fineness is 5-15 mu m to obtain the long-acting amoxicillin and colistin sulfate injection.
Example 3:
the long-acting amoxicillin and colistin sulfate injection comprises the following components in parts by weight: 9 parts of amoxicillin, 0.7 part of colistin sulfate, 1.5 parts of suspending agent, 1.2 parts of wetting agent, 0.4 part of antioxidant, 0.4 part of zinc oxide, 1 part of clavulanic acid, 2.2 parts of pH stabilizer and 100 parts of dispersion medium.
Wherein the suspending agent is a mixture of aluminum monostearate and cholesterol, and the mass ratio of the aluminum monostearate to the cholesterol in the suspending agent is 4: 1; the wetting agent is hydrogenated castor oil; the antioxidant is vitamin E; the preparation method of the pH stabilizer comprises the following steps: mixing potassium dihydrogen phosphate with a sodium hydroxide solution, and adding water for dilution, wherein the molar concentration of the sodium hydroxide solution is 0.1mol/L, and 0.65g of potassium dihydrogen phosphate and 15mL of the sodium hydroxide solution are added in each 100mL of water; the dispersion medium comprises soybean oil, benzyl benzoate and diacetin, and the mass ratio of the soybean oil to the benzyl benzoate to the diacetin is 1:0.7: 0.7.
A preparation method of a long-acting amoxicillin and colistin sulfate injection comprises the following steps:
1) respectively adding a suspending agent, a wetting agent, an antioxidant, zinc oxide, clavulanic acid and a pH stabilizer into a dispersion medium, and uniformly stirring to obtain a dispersion liquid;
2) adding the dispersion into a colloid mill, and starting the colloid mill;
3) adding amoxicillin and colistin sulfate into a colloid mill respectively to obtain a suspension, and grinding the suspension until the particle fineness is 5-15 mu m to obtain the long-acting amoxicillin and colistin sulfate injection.
Example 4:
the long-acting amoxicillin and colistin sulfate injection comprises the following components in parts by weight: 11 parts of amoxicillin, 0.5 part of colistin sulfate, 2.5 parts of a suspending agent, 0.8 part of a wetting agent, 0.7 part of an antioxidant, 0.3 part of zinc oxide, 1.2 parts of clavulanic acid, 1.7 parts of a pH stabilizer and 120 parts of a dispersion medium.
Wherein the suspending agent is a mixture of aluminum monostearate and cholesterol, and the mass ratio of the aluminum monostearate to the cholesterol in the suspending agent is 5: 1; the wetting agent is hydrogenated castor oil; the antioxidant is sodium formaldehyde sulfoxylate; the preparation method of the pH stabilizer comprises the following steps: mixing potassium dihydrogen phosphate with a sodium hydroxide solution, and adding water for dilution, wherein the molar concentration of the sodium hydroxide solution is 0.08mol/L, and 0.62g of potassium dihydrogen phosphate and 14mL of the sodium hydroxide solution are added in each 100mL of water; the dispersion medium comprises soybean oil, benzyl benzoate and diacetin, and the mass ratio of the soybean oil to the benzyl benzoate to the diacetin is 1:0.6: 0.8.
A preparation method of a long-acting amoxicillin and colistin sulfate injection comprises the following steps:
1) respectively adding a suspending agent, a wetting agent, an antioxidant, zinc oxide, clavulanic acid and a pH stabilizer into a dispersion medium, and uniformly stirring to obtain a dispersion liquid;
2) adding the dispersion into a colloid mill, and starting the colloid mill;
3) adding amoxicillin and colistin sulfate into a colloid mill respectively to obtain a suspension, and grinding the suspension until the particle fineness is 5-15 mu m to obtain the long-acting amoxicillin and colistin sulfate injection.
Example 5:
the long-acting amoxicillin and colistin sulfate injection comprises the following components in parts by weight: 10 parts of amoxicillin, 0.6 part of colistin sulfate, 2 parts of suspending agent, 1 part of wetting agent, 0.5 part of antioxidant, 0.35 part of zinc oxide, 1.1 part of clavulanic acid, 2 parts of pH stabilizer and 110 parts of dispersion medium.
Wherein the suspending agent is a mixture of aluminum monostearate and cholesterol, and the mass ratio of the aluminum monostearate to the cholesterol in the suspending agent is 3: 1; the wetting agent is hydrogenated castor oil; the antioxidant is vitamin E; the preparation method of the pH stabilizer comprises the following steps: mixing potassium dihydrogen phosphate with a sodium hydroxide solution, and adding water for dilution, wherein the molar concentration of the sodium hydroxide solution is 0.12mol/L, and 0.68g of potassium dihydrogen phosphate and 16mL of the sodium hydroxide solution are added in each 100mL of water; the dispersion medium comprises soybean oil, benzyl benzoate and diacetin, and the mass ratio of the soybean oil to the benzyl benzoate to the diacetin is 1:0.9: 0.6.
A preparation method of a long-acting amoxicillin and colistin sulfate injection comprises the following steps:
1) respectively adding a suspending agent, a wetting agent, an antioxidant, zinc oxide, clavulanic acid and a pH stabilizer into a dispersion medium, and uniformly stirring to obtain a dispersion liquid;
2) adding the dispersion into a colloid mill, and starting the colloid mill;
3) adding amoxicillin and colistin sulfate into a colloid mill respectively to obtain a suspension, and grinding the suspension until the particle fineness is 5-15 mu m to obtain the long-acting amoxicillin and colistin sulfate injection.
The results of the performance tests on the long acting amoxicillin and colistin sulfate injections prepared in examples 1-5 are shown in the following table:
wherein, the accelerated test is carried out under the conditions of 40 +/-2 ℃ of temperature and 65 +/-5% of relative humidity.
From the above results, it can be seen that example 5 is the best process, and through microscopic observation, both ends are cylindrical crystals, the average particle size of the suspension is 8.18 μm, the sedimentation ratio is 1.0, and after 6 months of accelerated test, the content has not changed significantly, and the property is stable.
The long-acting amoxicillin and colistin sulfate injection prepared in the example 5 is subjected to pharmacokinetic study, and the specific process is as follows:
the 12 yorkshire pigs were randomly divided into two groups, the first group was intramuscularly injected with the long-acting amoxicillin colistin sulfate injection prepared in example 5, and the second group was intramuscularly injected with the conventional amoxicillin colistin sulfate injection (amoxicillin 10 wt% + colistin sulfate 0.85 wt%), measured as 0.2mL per 1kg body weight. Then 10mL of blood is collected from the anterior vena cava at 0.25, 0.50, 0.75, 1.00, 2.00, 3.00, 5.00, 9.00, 12.00, 24.00, 36.00, 48.00, 60.00, 72.00, 96.00 and 108.00 hours, the blood concentration of the blood sample is analyzed by HPLC, and the relevant kinetic parameters are obtained by fitting processing by using MCPKP software, and are shown in the following table:
| first group | Second group | |
| Cmax | 12.52±1.32μg/mL | 18.47±1.94μg/mL |
| Tmax | 0.712h | 0.741h |
| t1/2β | 20.35±2.12h | 9.97±1.82h |
As can be seen from the above table, the long-acting amoxicillin and colistin sulfate injection prepared in example 5 can prolong the drug metabolism time.
The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make improvements and modifications within the scope of the present invention based on the disclosure of the present invention.
Claims (8)
1. The long-acting amoxicillin and colistin sulfate injection is characterized by comprising the following components in parts by weight: 8-12 parts of amoxicillin, 0.2-0.9 part of colistin sulfate, 1-3 parts of suspending agent, 0.5-1.5 parts of wetting agent, 0.3-0.8 part of antioxidant, 0.2-0.5 part of zinc oxide, 0.8-1.5 parts of clavulanic acid, 1.2-2.5 parts of pH stabilizer and 80-150 parts of dispersion medium;
the preparation method of the pH stabilizer comprises the following steps: mixing potassium dihydrogen phosphate with a sodium hydroxide solution, and adding water for dilution, wherein the molar concentration of the sodium hydroxide solution is 0.05-0.15mol/L, and 0.6-0.7g of potassium dihydrogen phosphate and 12-18mL of the sodium hydroxide solution are added in each 100mL of water;
the dispersion medium consists of soybean oil, benzyl benzoate and diacetin, and the mass ratio of the soybean oil to the benzyl benzoate to the diacetin is 1:0.5-1: 0.5-1;
the pH value of the injection is 6-7;
the preparation method of the injection specifically comprises the following steps:
1) respectively adding a suspending agent, a wetting agent, an antioxidant, zinc oxide, clavulanic acid and a pH stabilizer into a dispersion medium, and uniformly stirring to obtain a dispersion liquid;
2) adding the dispersion into a colloid mill, and starting the colloid mill;
3) and respectively adding amoxicillin and colistin sulfate into a colloid mill to obtain a suspension, and grinding to obtain the long-acting amoxicillin and colistin sulfate injection.
2. The long-acting amoxicillin and colistin sulfate injection as claimed in claim 1, which comprises the following components in parts by weight: 9-11 parts of amoxicillin, 0.5-0.7 part of colistin sulfate, 1.5-2.5 parts of suspending agent, 0.8-1.2 parts of wetting agent, 0.4-0.7 part of antioxidant, 0.3-0.4 part of zinc oxide, 1-1.2 parts of clavulanic acid, 1.7-2.2 parts of pH stabilizer and 120 parts of dispersion medium 100-.
3. The long-acting amoxicillin and colistin sulfate injection as claimed in claim 2, which comprises the following components in parts by weight: 10 parts of amoxicillin, 0.6 part of colistin sulfate, 2 parts of suspending agent, 1 part of wetting agent, 0.5 part of antioxidant, 0.35 part of zinc oxide, 1.1 part of clavulanic acid, 2 parts of pH stabilizer and 110 parts of dispersion medium.
4. The long-acting amoxicillin and colistin sulfate injection as claimed in claim 1, wherein the suspending agent is a mixture of aluminum monostearate and cholesterol, and the mass ratio of the aluminum monostearate to the cholesterol in the suspending agent is 3-5: 1.
5. The long-acting amoxicillin and colistin sulfate injection as claimed in claim 1, wherein the wetting agent is hydrogenated castor oil.
6. The long-acting amoxicillin and colistin sulfate injection as claimed in claim 1, wherein the antioxidant is vitamin E or sodium formaldehyde sulfoxylate.
7. A process for the preparation of a long acting amoxicillin and colistin sulfate injection as claimed in any one of claims 1 to 6, comprising the steps of:
1) respectively adding a suspending agent, a wetting agent, an antioxidant, zinc oxide, clavulanic acid and a pH stabilizer into a dispersion medium, and uniformly stirring to obtain a dispersion liquid;
2) adding the dispersion into a colloid mill, and starting the colloid mill;
3) and respectively adding amoxicillin and colistin sulfate into a colloid mill to obtain a suspension, and grinding to obtain the long-acting amoxicillin and colistin sulfate injection.
8. The preparation method of the long-acting amoxicillin and colistin sulfate injection as claimed in claim 7, wherein in the step 3), the fineness of the particles in the suspension is 5-15 μm.
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| CN108030912A (en) * | 2017-12-15 | 2018-05-15 | 合肥中龙神力动物药业有限公司 | A kind of Amoxicillin colistin sulphate suspension injection |
| CN110101837A (en) * | 2018-05-25 | 2019-08-09 | 四川伴农动保生物技术有限公司 | A kind of veterinary composition and its liquid preparation and preparation method |
| CN114533852A (en) * | 2022-02-25 | 2022-05-27 | 四川恒通动保生物科技有限公司 | Compound amoxicillin and colistin sulfate suspension injection and preparation method thereof |
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