WO2011147280A1

WO2011147280A1 - Injection of enrofloxacin and producing method thereof

Info

Publication number: WO2011147280A1
Application number: PCT/CN2011/074426
Authority: WO
Inventors: 董惠峰
Original assignee: 鼎正动物药业（天津）有限公司
Priority date: 2010-05-22
Filing date: 2011-05-20
Publication date: 2011-12-01
Also published as: AU2011257785A1; CN101810569A; CN101810569B; AU2011101749A4; KR20130080422A

Abstract

An injection of enrofloxacin and the producing method thereof are disclosed. The injection comprises from 10 to 20 parts of enrofloxacin, from 0.1 to 0.5 part of antioxidant and from 0.1 to 0.5 part of chelating agent and has a neutral pH value. The antioxidant is sodium bisulfite or sodium thiosulfate. The chelating agent is EDTA. The injection is stable and not irritative. Its producing method comprises the steps of: (1) adding enrofloxacin to the aqueous solution of sodium hydroxide; (2) continuing adding the aqueous solution of sodium hydroxide to obtain a pH value of 9-13; (3) adding acidifying agent to obtain a neutral pH value; (4) adding the antioxidant; (5) adding the chelating agent; (6) adding water to obtain the final product. The acidifying agent in step (3) is one or two or three selected from the group of lactic acid, sodium butyrate and arginine.

Description

Enrofloxacin injection and its preparation brigade

Technical field

The invention relates to an antibacterial medicine for preventing and controlling aquatic diseases of livestock and poultry, in particular to an enrofloxacin injection and a preparation method thereof. Background technique

Enrofloxacin (English name: Enrofloxacin), its chemical formula is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-ethyl-1-piperazinyl)- 3-quinolinecarboxylic acid (English name: 1, 4-dihydro-l-cyclopropyl-7- (4-ethyl-l-piperazinyl) -6~f luoro-4-oxo-3-quinol i

) is a representative of a new generation of quinolone antibacterial drugs. It is a special new drug for the prevention and control of aquatic diseases in livestock and poultry. It not only retains the characteristics of broad-spectrum, high-efficiency, low toxicity, good absorption and convenient administration of quinolones, but also various Various infections caused by bacteria have significant effects, especially for various mycoplasma. The killing power of various mycoplasma is significantly higher than other drugs of quinolones and various drugs such as tylosin and tyrosin which have been used for many years. However, since enrofloxacin has a very strong bitter taste, when used as an oral dosage form, the tolerance of the animal is very low, so it is usually administered in the form of an injection in clinical use. Enrofloxacin is very soluble in water and dissolves in alkaline solvents, so the commonly used injection is an alkaline aqueous solution of enrofloxacin, the alkaline aqueous solution is an aqueous solution of sodium hydroxide, but enrofloxacin is in an alkaline aqueous solution. The solubility in the solution was 10%, and the excess portion precipitated in a crystalline form. Moreover, when the sodium hydroxide aqueous solution containing enrofloxacin is injected into the animal body through a syringe, the biological environment in the animal body is weakly acidic, and when the alkaline aqueous solution is injected, the animal is stimulated more, the animal Will show a significant discomfort. . Summary of the invention

The object of the present invention is to overcome the deficiencies of the prior art, and to provide an enrofloxacin injection having a neutral pH and no stimulation to an animal, wherein the content of enrofloxacin in the injection is 10 to 20%. It greatly increases the therapeutic effect of single administration, and the prepared enrofloxacin injection has stable traits and long-term storage without crystallization, which is a kind of injection with good therapeutic effect and no stimuli.

5份。 The espresso agent is 0. 1~0. 5 parts. The chelating agent is 0. 1~0. 5 parts. The enrofloxacin accounts for 10 to 20% of the total weight of the solution. The antioxidant is sodium thiosulfate or sodium hydrogen sulfite. The chelating agent is EDTA. The invention also provides a preparation method of enrofloxacin injection, the method comprising the following steps:

(1) adding enrofloxacin to an aqueous solution of sodium hydroxide;

(2) continue to add sodium hydroxide solution to adjust the pH to 9~13;

(3) adding an acidifying agent to adjust the pH to neutral;

(4) adding an antioxidant;

(5) adding a chelating agent;

(6) Enrofloxacin injection was prepared after constant volume with water.

After the step (6) is completed, the sterilizing treatment is performed by using a 45.

4摩尔/l。 The concentration of the aqueous solution of the aqueous solution of the aqueous solution of the aqueous solution of the aqueous solution of the aqueous solution of the aqueous solution of the aqueous solution of the aqueous solution of the aqueous solution of the aqueous solution of The acidifying agent in the step (3) is one or two or three kinds of lactic acid, sodium butyrate or arginine. The antioxidant in step (4) is sodium thiosulfate or sodium hydrogen sulfite. The chelating agent in step (5) is EDTA. The water in the step (6) is purified water.

The advantages and positive effects of the present invention are as follows: the enrofloxacin injection prepared by the present invention is added with one or two or three kinds of lactic acid, sodium butyrate or arginine, and finally the pH of the injection is made. Neutral, which is not irritating when the animal is injected, and increases the amount of enrofloxacin in the injection to 20%, greatly increasing the therapeutic effect of a single administration, and simultaneously preparing the enrofloxacin injection. It has stable liquid properties and long-term storage without crystal precipitation. It is a kind of injection with good therapeutic effect and no stimulation. detailed description

The following examples are intended to be illustrative of the invention, and are not intended to limit the scope of the invention.

5份。 The present invention, the singularity of the singularity of the singularity of the singularity of the singularity of the singularity of the singularity. 5份。 The chelating agent 0. 1~0. 5 parts. Enrofloxacin accounts for 10 to 20% of the total weight of the solution. The antioxidant is sodium thiosulfate or sodium hydrogen sulfite. The chelating agent is EDTA (Ethyl ene Diamine Tetraacet i c Ac i d).

Example 1

A method for preparing enrofloxacin injection comprises the following steps:

(1) 20 g of enrofloxacin was added to a 60 ml aqueous sodium hydroxide solution having a concentration of 0.4 mol/l, and stirred until all enrofloxacin was dissolved;

(2) continue to add a concentration of 0. 4mol / l of sodium hydroxide solution to adjust the pH to 12;

(3) Add 20ml of acidifier lactic acid. In the process of adding acidifier, first, enrofloxacin will precipitate crystals. The addition of an acidifying agent, when the pH is neutral, all enrofloxacin is dissolved;

(4) The neutral solution was added with 0.5 g of sodium thiosulfate antioxidant;

(5) continue to add 0. 5g of EDTA chelating agent;

(6) Step (5) After completion, the volume is adjusted to 100 ml with purified water, and the solution after constant volume is filtered through a microporous membrane of 0. 45 um;

(7) Filtering the sterilized injection solution to prepare the finished product.

The enrofloxacin injection was tested to be neutral, and the enzyfloxacin content of the active ingredient in the solution injection was 20% of the total weight of the injection solution.

Example 2

A method for preparing enrofloxacin injection comprises the following steps:

(1) 15 g of enrofloxacin was added to a 70 ml aqueous solution of sodium hydroxide at a concentration of 0.3 mol/l, stirred, and enrofloxacin was partially dissolved, and another portion of enrofloxacin was present as a precipitate;

(2) Continue to add a sodium hydroxide aqueous solution having a concentration of 0.3 mol/l to adjust the pH to 11, and then the enrofloxacin is completely dissolved.

(3) Adding 0.15 g of acidifier sodium butyrate and 10 ml of lactic acid. During the addition of the acidifying agent, the enrofloxacin crystals will continue to precipitate in the solution. With the addition of the acidifying agent, the pH is neutral. When enrofloxacin is completely dissolved;

(4) adding 0.4 g of sodium hydrogen sulfite antioxidant in a neutral solution;

(5) continue to add 0. 4g of EDTA chelating agent;

The enrofloxacin injection was tested to be neutral, and the enolfloxacin content of the active ingredient in the solution was

15%.

Example 3

A method for preparing enrofloxacin injection comprises the following steps:

(1) 10 g of enrofloxacin was added to a 60 ml aqueous solution of sodium hydroxide at a concentration of 0.2 mol/l, stirred, and enrofloxacin was partially dissolved, and another portion of enrofloxacin was present as a precipitate;

(2) Continue to add a concentration of 0.5 mol of sodium hydroxide to adjust the pH to 13, until enrofloxacin is completely dissolved.

(3) Add 15ml of acidifying agent lactic acid. During the addition of acidifying agent, enrofloxacin crystals will continue to precipitate in the solution. With the addition of acidifying agent, enrofloxacin is completely dissolved when the pH is neutral. ;

(1) lg sodium thiosulfate antioxidant; (5) continued to add 0. lg of EDTA chelating agent;

10%.

Example 4

A method for preparing enrofloxacin injection comprises the following steps:

(1) 18 g of enrofloxacin was added to a 60 ml aqueous solution of sodium hydroxide having a concentration of 0.4 mol/l, and stirred until all of enrofloxacin was dissolved;

(3) Adding 16ml of acidifying agent lactic acid, in the process of adding acidifier, first, enrofloxacin will precipitate crystals. With the addition of acidifying agent, when the pH value is neutral, all the enrofloxacin is dissolved;

(5) continue to add 0. 3g of EDTA chelating agent;

The enrofloxacin injection was tested to be neutral, and the enzyfloxacin content of the active ingredient in the solution was 18%.

Liquid no precipitation solution No liquid No precipitation liquid No precipitation liquid No precipitation solution No crystal precipitation precipitate Crystal crystal crystallization precipitated crucible Example 4 Light yellow soluble light yellow light yellow light yellow soluble light yellow soluble light yellow liquid without precipitation Solution without liquid, no precipitate, no precipitate, no precipitation solution, no sputum, precipitate, precipitate, sputum, Table 1: Stability test of enrofloxacin injection

As can be seen from Table 1, the enrofloxacin injection prepared by the present invention has stable composition and no precipitation during long-term storage.

Table 2: Adverse effects of enrofloxacin injection on animals

As can be seen from Table 2, the enrofloxacin injection prepared by the present invention is not irritating to the animal, and the animal has no uncomfortable reaction after the administration.

Table 3: Test results of therapeutic effect of chicken artificially infected Escherichia coli As can be seen from Table 3, the enrofloxacin injection prepared by the present invention has good curative effect and high cure rate.

Claims

Claim

The chelating agent is a chelating agent. The chelating agent is 0. 1~0. 5 parts, a chelating agent. 0. 1~0. 5份。

The enrofloxacin injection according to claim 1, wherein the enrofloxacin accounts for 10 to 20% of the total weight of the injection solution.

3. An enrofloxacin injection according to claim 1, wherein the antioxidant is sodium thiosulfate or sodium hydrogen sulfite.

4. An enrofloxacin injection according to claim 1, wherein the chelating agent is EDTA.

5. A method for preparing enrofloxacin injection, comprising: the following steps:

(1) adding enrofloxacin to an aqueous solution of sodium hydroxide;

(2) continue to add sodium hydroxide solution to adjust the pH to 9~13;

(3) adding an acidifying agent to adjust the pH to neutral;

(4) adding an antioxidant;

(5) adding a chelating agent;

(6) Enrofloxacin injection was prepared after constant volume with water.

The method for preparing enrofloxacin injection according to claim 5, wherein: after the step (6) is completed, a 0.44 μm microfiltration membrane filtration sterilization treatment is performed.

2 〜 0. 4mol/l _{0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0}

8. A method of preparing enrofloxacin injection according to claim 5, wherein: said step

The acidifying agent in (3) is one or two or three kinds of lactic acid, sodium butyrate or arginine.

9. A method of preparing enrofloxacin injection according to claim 5, wherein: said step

The antioxidant in (4) is sodium thiosulfate or sodium hydrogen sulfite.

The method for preparing enrofloxacin injection according to claim 5, wherein the chelating agent in the step (5) is EDTA.