CN109431981B - Enrofloxacin injection and preparation method thereof - Google Patents
Enrofloxacin injection and preparation method thereof Download PDFInfo
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- CN109431981B CN109431981B CN201811414845.XA CN201811414845A CN109431981B CN 109431981 B CN109431981 B CN 109431981B CN 201811414845 A CN201811414845 A CN 201811414845A CN 109431981 B CN109431981 B CN 109431981B
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- injection
- enrofloxacin
- meglumine
- water
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Abstract
The application discloses a preparation method of enrofloxacin injection, which comprises the following steps: the method comprises the following steps: (1) heating injection water accounting for 40 percent of the total amount to 80 ℃, and adding meglumine and hydroxymethyl cellulose according to the prescription amount until the meglumine and the hydroxymethyl cellulose are dissolved; (2) dissolving the antioxidant and the chelating agent in the prescription amount by using 20 percent of the total amount of the water for injection, and adding the mixture into the solution in the step (1) under the stirring state; (3) adding enrofloxacin and propylene glycol into the solution in the step (2), mixing, and performing ultrasonic treatment for 5-10 min; adding 8-13 wt% acetic acid to adjust the pH value of the mixed solution to 5.4-6.8 during the ultrasonic treatment; (4) coarse-filtering with 0.45 μm microporous filter membrane; (5) adding water for injection to full volume, and fine filtering with 0.22 μm microporous membrane; (6) and subpackaging the filtered solution. The preparation method effectively solves the technical problems of the existing enrofloxacin injection.
Description
Technical Field
The application relates to the technical field of medicines, in particular to enrofloxacin injection and a preparation method thereof.
Background
Enrofloxacin can be used as animal medicine, has long half-life period in animal body, good tissue distribution, belongs to broad-spectrum bacteriostat, has bacteriostasis effect on gram-positive bacteria, gram-negative bacteria and mildews, and is used for controlling vibriosis and colibacillosis diseases of cultured fishes.
The existing enrofloxacin injection and the preparation method thereof have some defects. Firstly, the solubility of enrofloxacin in water is low; secondly, the phase solubility is improved mainly by adding sodium hydroxide and the like at present, but the injection has higher alkalinity after the sodium hydroxide is added, and the biological environment in the animal body is weak acidic, so the animal is stimulated greatly; thirdly, the traditional enrofloxacin injection has poor stability and is easy to generate crystallization; fourthly, the enrofloxacin injection has quick effect but low persistence, so that the existing whole dosage is large, other toxic and side effects are easy to generate, and the injection with lasting effect and low dosage is urgently needed.
Disclosure of Invention
The invention provides an enrofloxacin injection and a preparation method thereof, and the preparation method effectively solves the problems of the existing enrofloxacin injection. The technical scheme of the invention is as follows:
the enrofloxacin injection comprises the following components:
10-28 wt% enrofloxacin;
5-32 wt% propylene glycol;
8-13 wt% acetic acid;
0.5-17 wt% meglumine;
5-9.6 wt% of hydroxymethyl cellulose;
the rest is water for injection.
Optionally, the injection system has a pH of 5.4-6.8.
Optionally, the injection comprises:
20 wt% enrofloxacin;
30 wt% propylene glycol;
12 wt% acetic acid;
5 wt% meglumine;
4 wt% of hydroxymethyl cellulose;
the rest is water for injection.
Optionally, the enrofloxacin injection also comprises an antioxidant and/or a complexing agent. The antioxidant is sodium bisulfite; the complexing agent is EDTA-2 Na. The content of sodium bisulfite is 0.1-0.3 wt%; the content of EDTA-2Na is 0.01-0.05 wt%.
Optionally, the sodium bisulfite content is 0.2 wt%; the content of EDTA-2Na is 0.03 wt%. The preparation method of the enrofloxacin injection comprises the following steps:
(1) heating injection water accounting for 40 percent of the total amount to 80 ℃, and adding meglumine and hydroxymethyl cellulose according to the prescription amount until the meglumine and the hydroxymethyl cellulose are dissolved;
(2) dissolving the antioxidant and the chelating agent in the prescription amount by using 20 percent of the total amount of the water for injection, and adding the mixture into the solution in the step (1) under the stirring state;
(3) adding enrofloxacin and propylene glycol into the solution in the step (2), mixing, and performing ultrasonic treatment for 5-10 min; adding 8-13 wt% acetic acid to adjust the pH value of the mixed solution to 5.4-6.8 during the ultrasonic treatment;
(4) coarse-filtering with 0.45 μm microporous filter membrane;
(5) adding water for injection to full volume, and fine filtering with 0.22 μm microporous membrane;
(6) and subpackaging the filtered solution.
The invention has the following technical effects:
(1) in a weakly acidic enrofloxacin injection system, the solubility of enrofloxacin can be remarkably improved by adopting propylene glycol; (2) the stability of the enrofloxacin injection system can be improved by adding the hydroxymethyl cellulose into the enrofloxacin injection, and the stability of the enrofloxacin injection system is improved and the enrofloxacin injection has obvious slow release performance after the propylene glycol-carboxymethyl cellulose system is adopted and subjected to ultrasonic dispersion. (3) The invention utilizes the dissolution assisting effect of the meglumine to salify the meglumine and the enrofloxacin, thereby not only promoting the dissolution of the enrofloxacin, but also reducing the usage amount of acetic acid. (4) The injection of embodiment 2 of the invention has high stability and excellent slow release effect.
Detailed Description
Example 1
The enrofloxacin injection comprises the following components:
20 wt% enrofloxacin;
30 wt% propylene glycol;
12 wt% acetic acid;
5 wt% meglumine;
4 wt% of hydroxymethyl cellulose;
the rest is water for injection.
The preparation method comprises the following steps:
(1) heating injection water accounting for 40 percent of the total amount to 80 ℃, and adding meglumine and hydroxymethyl cellulose according to the prescription amount until the meglumine and the hydroxymethyl cellulose are dissolved;
(2) adding enrofloxacin and propylene glycol into the solution obtained in the step (1), mixing, and performing ultrasonic treatment for 8 min; adding 10 wt% acetic acid to adjust the pH value of the mixed solution to 5.8 in the ultrasonic treatment process;
(3) coarse-filtering with 0.45 μm microporous filter membrane;
(4) adding water for injection to full volume, and fine filtering with 0.22 μm microporous membrane;
(5) and subpackaging the filtered solution.
Example 2
The enrofloxacin injection comprises the following components:
20 wt% enrofloxacin;
30 wt% propylene glycol;
12 wt% acetic acid;
5 wt% meglumine;
4 wt% of hydroxymethyl cellulose;
the content of sodium bisulfite is 0.2 wt%;
the content of EDTA-2Na is 0.03 wt%;
the rest is water for injection.
The preparation method comprises the following steps:
(1) heating injection water accounting for 40 percent of the total amount to 80 ℃, and adding meglumine and hydroxymethyl cellulose according to the prescription amount until the meglumine and the hydroxymethyl cellulose are dissolved;
(2) dissolving the antioxidant and the chelating agent in the prescription amount by using 20 percent of the total amount of the water for injection, and adding the mixture into the solution in the step (1) under the stirring state;
(3) adding enrofloxacin and propylene glycol into the solution in the step (2), mixing, and performing ultrasonic treatment for 8 min; adding 10 wt% acetic acid to adjust the pH value of the mixed solution to 5.8 in the ultrasonic treatment process;
(4) coarse-filtering with 0.45 μm microporous filter membrane;
(5) adding water for injection to full volume, and fine filtering with 0.22 μm microporous membrane;
(6) and subpackaging the filtered solution.
Example 3
The enrofloxacin injection comprises the following components:
10 wt% enrofloxacin;
30 wt% propylene glycol;
12 wt% acetic acid;
12 wt% meglumine;
5 wt% of hydroxymethyl cellulose;
the rest is water for injection. The preparation method is the same as that of example 1.
Example 4
The enrofloxacin injection comprises the following components:
28 wt% enrofloxacin;
7% by weight of propylene glycol;
8 wt% acetic acid;
0.5 wt% meglumine;
9 wt% of hydroxymethyl cellulose;
the content of sodium bisulfite is 0.2 wt%;
the content of EDTA-2Na is 0.03 wt%;
the rest is water for injection. The preparation method is the same as that of example 2.
Comparative example 1
The composition and preparation process were substantially the same as those of example 1 except that glycerin was used instead of propylene glycol.
Comparative example 2
The composition and preparation method were substantially the same as in example 1, except that hydroxymethylcellulose was not added.
The basic characteristics of the enrofloxacin injection are determined by adopting visual observation, pH value determination, centrifugal acceleration test and stability constant, wherein the centrifugal rotating speed is 5000 r/min/time is 10 min. Stability (Ke value). The enrofloxacin injection solutions of examples 1 to 4 and comparative examples 1 to 2 were injected in an amount of 10mg/kg in test animals (sheep) and tested for half-life.
The experimental results for each example are as follows:
it can be seen from the results of the above examples that the stability of examples 1-4 is less, and the stability is correspondingly greatly improved over that of the comparative example. The stability of the propylene glycol-hydroxymethyl cellulose system is obviously improved after ultrasonic dispersion, and the propylene glycol or hydroxymethyl cellulose which is singly adopted has poor stability. Example 2 also has a small increase in half-life relative to example 1, which shows that the addition of the antioxidant and the complexing agent further improves the slow release performance of the system in addition to the antioxidant and complexing effects of the antioxidant and the complexing agent, and achieves an unexpected technical effect.
The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and various modifications and changes will occur to those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (2)
1. The preparation method of the enrofloxacin injection is characterized by comprising the following components:
20 wt% enrofloxacin;
30 wt% propylene glycol;
12 wt% acetic acid;
5 wt% meglumine;
4 wt% of hydroxymethyl cellulose;
the rest is water for injection;
the preparation method comprises the following preparation steps:
(1) heating injection water accounting for 40 percent of the total amount to 80 ℃, and adding meglumine and hydroxymethyl cellulose according to the prescription amount until the meglumine and the hydroxymethyl cellulose are dissolved;
(2) adding enrofloxacin and propylene glycol into the solution obtained in the step (1), mixing, and performing ultrasonic treatment for 8 min; adding 10 wt% acetic acid to adjust the pH value of the mixed solution to 5.8 in the ultrasonic treatment process;
(3) coarse-filtering with 0.45 μm microporous filter membrane;
(4) adding water for injection to full volume, and fine filtering with 0.22 μm microporous membrane;
(5) and subpackaging the filtered solution.
2. The preparation method of the enrofloxacin injection is characterized by comprising the following components:
20 wt% enrofloxacin;
30 wt% propylene glycol;
12 wt% acetic acid;
5 wt% meglumine;
4 wt% of hydroxymethyl cellulose;
0.2 wt% sodium bisulfite;
0.03wt％EDTA-2Na；
the rest is water for injection;
the preparation method comprises the following preparation steps:
(1) heating injection water accounting for 40 percent of the total amount to 80 ℃, and adding meglumine and hydroxymethyl cellulose according to the prescription amount until the meglumine and the hydroxymethyl cellulose are dissolved;
(2) dissolving the antioxidant and the chelating agent in the prescribed amount by using 20 percent of the total amount of water for injection, and adding the mixture into the solution in the step (1) under the stirring state;
(3) adding enrofloxacin and propylene glycol into the solution in the step (2), mixing, and performing ultrasonic treatment for 8 min; adding 10 wt% acetic acid to adjust the pH value of the mixed solution to 5.8 in the ultrasonic treatment process;
(4) coarse-filtering with 0.45 μm microporous filter membrane;
(5) adding water for injection to full volume, and fine filtering with 0.22 μm microporous membrane;
(6) and subpackaging the filtered solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811414845.XA CN109431981B (en) | 2018-11-26 | 2018-11-26 | Enrofloxacin injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811414845.XA CN109431981B (en) | 2018-11-26 | 2018-11-26 | Enrofloxacin injection and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109431981A CN109431981A (en) | 2019-03-08 |
| CN109431981B true CN109431981B (en) | 2020-02-14 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811414845.XA Active CN109431981B (en) | 2018-11-26 | 2018-11-26 | Enrofloxacin injection and preparation method thereof |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001045727A2 (en) * | 1999-12-20 | 2001-06-28 | New Pharma Research Sweden Ab | Stabilized veterinary compositions comprising more than one antiviral agent |
| CN102415991A (en) * | 2011-11-24 | 2012-04-18 | 陈鹏举 | Enrofloxacin long-acting injection and preparation method thereof |
| CN103830168A (en) * | 2012-11-26 | 2014-06-04 | 青岛宝依特生物制药有限公司 | Preparation method of enrofloxacin long-acting injection |
| CN104288152A (en) * | 2014-09-15 | 2015-01-21 | 江西核工业瑞丰生物药业有限公司 | Compound berberine sulfate injection for veterinary use and preparation method thereof |
-
2018
- 2018-11-26 CN CN201811414845.XA patent/CN109431981B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001045727A2 (en) * | 1999-12-20 | 2001-06-28 | New Pharma Research Sweden Ab | Stabilized veterinary compositions comprising more than one antiviral agent |
| CN102415991A (en) * | 2011-11-24 | 2012-04-18 | 陈鹏举 | Enrofloxacin long-acting injection and preparation method thereof |
| CN103830168A (en) * | 2012-11-26 | 2014-06-04 | 青岛宝依特生物制药有限公司 | Preparation method of enrofloxacin long-acting injection |
| CN104288152A (en) * | 2014-09-15 | 2015-01-21 | 江西核工业瑞丰生物药业有限公司 | Compound berberine sulfate injection for veterinary use and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| Pharmacokinetics of enrofloxacin and ciprofloxacin in Atlantic horseshoe crabs (Limulus polyphemus) after single injection;Kirby A.等;《JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS》;20180430;第41卷(第2期);第349-353页 * |
| 正交设计优选复方恩诺沙星混悬型注射剂处方的研究;符华林等;《黑龙江畜牧兽医》;20071231(第10期);第92-94页 * |
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| CN109431981A (en) | 2019-03-08 |
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