CN105012320A - Preparation technology for compound solution of florfenicol and doxycycline - Google Patents
Preparation technology for compound solution of florfenicol and doxycycline Download PDFInfo
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- CN105012320A CN105012320A CN201510427181.0A CN201510427181A CN105012320A CN 105012320 A CN105012320 A CN 105012320A CN 201510427181 A CN201510427181 A CN 201510427181A CN 105012320 A CN105012320 A CN 105012320A
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- florfenicol
- doxycycline
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Abstract
The invention relates to the technical field of veterinary medicines, in particular to a preparation technology for compound solution of florfenicol and doxycycline. The preparation technology has the advantages that since the solution is prepared from doxycycline hydrochloride, stress reaction of livestock and poultry is reduced during dosing, contact area of medicine and the absorption part is enlarged, release of the medicine in an acid environment of the stomach is reduced by means of complexation of magnesium ions and the doxycycline hydrochloride, stimulus of the doxycycline hydrochloride to gastric mucosa is avoided effectively, the medicine is transferred to the absorption part of the small intestine directly, and clinical medicinal value of the doxycycline is increased; the florfenicol is added into a doxycycline hydrochloride solution, and the problem of solubility of the florfenicol is solved by the aid of different proportions of corresponding solvents and employing of solubilizing agents.
Description
Technical field
The present invention relates to veterinary drug technical field, particularly the preparation technology of a kind of florfenicol and compound doxycycline solution.
Background technology
Fowl bacterial disease is the common frdquently encountered disease in current scale livestock farming and raiser's breeding process, has become the principal element of harm poultry industry development.Treatment bacterial disease, florfenicol and doxycycline conbined usage can expand antimicrobial spectrum and heighten the effect of a treatment, and have become the classical formula of Clinical practice.
But " People's Republic of China's veterinary drug allusion quotation " Bio-Tab that version was included in 2010 is for poultry at present, administration is inconvenient, adds the irritability of animal, and easily causes injury to alimentary tract and gastric ulcer.Doxycycline is shown in that light heat is easily oxidized, therefore the stability of doxycycline solution becomes critical technological point prepared by this dosage form.
Summary of the invention
In order to solve the problem of prior art, the invention provides the preparation technology of a kind of florfenicol and compound doxycycline solution, doxycycline hydrochloride is made solution by it, reduce the stress of poultry in administration process, expand the contact area of medicine and absorption site, magnesium ion and doxycycline hydrochloride complexation is utilized to discharge at stomach sour environment to reduce medicine, effectively avoid doxycycline hydrochloride to the stimulation of gastric mucosa, by direct delivery of drugs to intestinal absorption site, thus improve the clinical medical value of doxycycline.
Florfenicol joins in doxycycline solution by the present invention simultaneously, utilizes the different ratio of coordinative solvent and the use of solubilizing agent, solves the deliquescent problem of florfenicol.For veterinary clinic use provides a kind of with low cost, easy to use, the compound recipe solution of determined curative effect.
The technical solution adopted in the present invention is as follows:
A preparation technology for florfenicol and compound doxycycline solution, comprises the following steps:
A, the ratio of doxycycline and chelating agent 1:2 ~ 8:1 in mass ratio slowly to be joined in organic solvent;
B, solution steps A obtained are heated to 40 ~ 80 DEG C, and continuous uniform stirs 20 ~ 100 minutes
Slowly add florfenicol in C, the solution that obtains in step B, described florfenicol and doxycycline weight ratio are 1:2 ~ 2:1, are stirred to dissolving, as organic facies;
D, antioxidant, water soluble polymer, solubilizing agent to be added to the water by its weight ratio 0.01% ~ 5% in final mean annual increment solution agent, be stirred to dissolving, as inorganic phase, described antioxidant, water soluble polymer, solubilizing agent part by weight is each other 1:10 ~ 20:10 ~ 80;
E, above-mentioned inorganic phase slowly to be joined in organic facies, stir 20 ~ 60 minutes.
Organic solvent in steps A is the mixture of one or more in dimethyl formamide, dimethyl acetylamide, propylene glycol, ethanol, alpha-pyrrolidone, N-Methyl pyrrolidone, glycerol, ethyl acetate.
Antioxidant in step D is the mixture of one or more in Butylated hydroxyanisole, dibenzylatiooluene, propyl gallate, tertiarybutylhydroquinone, sodium pyrosulfite, sodium sulfite, sodium sulfite, sodium thiosulfate.
Chelating agent in steps A is the mixture of one or more in citric acid, EDTA and Quadrafos.
Water soluble polymer in step D is the mixture of one or more in gelatin, polyvinyl alcohol, Polyethylene Glycol, polyvidone.
Solubilizing agent in step D is the mixture of one or more in polysorbate 20, polysorbate 40, polyoxyethylene sorbitan monoleate, polyvidone, polyoxyethylene castor oil.
The beneficial effect that technical scheme provided by the invention is brought is:
Doxycycline hydrochloride is made solution by the present invention, not only reduce the stress of poultry in administration process, the contact area of medicine and absorption site can also be expanded, in the preparation of this solution, utilize magnesium ion and doxycycline hydrochloride complexation to discharge at stomach sour environment to reduce medicine, can effectively avoid doxycycline hydrochloride to the stimulation of gastric mucosa like this, by direct delivery of drugs to intestinal absorption site, thus the clinical medical value of doxycycline can be improved again.
Add antioxidant in formula of the present invention, ensure that the stability of doxycycline in solution, solve it and see the oxidizable decomposition of light, the technical barrier of solution instability.
The present invention adds solubilizing agent, solves the technical barrier that florfenicol chance elutriation goes out.
Florfenicol and doxycycline are made compound recipe solution by the present invention, expand antimicrobial spectrum, enhance clinical efficacy, reduce production cost, facilitate clinical administration, reduce poultry irritability, avoid a kind of antibiotic of Reusability simultaneously and make pathogenic microorganism produce the defect of drug resistance.
Detailed description of the invention
For making the object, technical solutions and advantages of the present invention clearly, be described in further detail below in conjunction with embodiment.
Embodiment 1
Get doxycycline 10g, citric acid 1.3g, add dimethyl acetylamide 35g, 45 DEG C of heating, stir 40min.
Slowly add 10g florfenicol while stirring, be stirred to dissolving, glycerol adding 35g, as organic facies.
Get sodium pyrosulfite 0.2g, EDTA 0.1g, PEG400 2g, polyoxyethylene sorbitan monoleate 4g adds in 15g purified water successively, be stirred to dissolving, as inorganic phase.
Above-mentioned inorganic phase is slowly joined in organic facies, stirs 20min, the florfenicol-compound doxycycline solution prescription of obtained the present embodiment.
Apply the broiler group of this preparation to a routine ehec infection disease to treat, its effective percentage reaches 85%.
Embodiment 2
Get doxycycline 5g, citric acid 10g, add dimethyl formamide 25g, 50 DEG C of heating, stir 45min.
Slowly add 10g florfenicol while stirring, be stirred to dissolving, add propylene glycol 50g, as organic facies.
Get sodium sulfite 0.2g, citric acid 0.1g, PEG400 2g, polyoxyethylene sorbitan monoleate 2g add in 10g purified water successively, be stirred to dissolving, as inorganic phase.
Above-mentioned inorganic phase is slowly joined in organic facies, stirs 20min, the florfenicol-compound doxycycline solution prescription of obtained the present embodiment.
Apply the broiler group of this preparation to a routine ehec infection disease to treat, its cure rate reaches 90%.
Embodiment 3
Get doxycycline 10g, citric acid 5g, add alpha-pyrrolidone 30g, 55 DEG C of heating, stir 50min.
Slowly add 5g florfenicol while stirring, be stirred to dissolving, glycerol adding 40g, as organic facies.
Get sodium sulfite 0.1g, EDTA 0.1g, gelatin 2g, polysorbate 40 4g adds in 15g purified water successively, be stirred to dissolving, as inorganic phase.
Above-mentioned inorganic phase is slowly joined in organic facies, stirs 30min, the florfenicol-compound doxycycline solution prescription of obtained the present embodiment.
Apply the broiler group of this preparation to a routine ehec infection disease to treat, its cure rate reaches 88%.
Embodiment 4
Get doxycycline 5g, citric acid 10g, add N-Methyl pyrrolidone 35g, 60 DEG C of heating, stir 55min.
Slowly add 5g florfenicol while stirring, be stirred to dissolving, add ethanol 40g, as organic facies.
Get sodium thiosulfate 0.1g, citric acid 0.1g, gelatin 2g, polysorbate 40 4g add in 15g purified water successively, be stirred to dissolving, as inorganic phase.
Above-mentioned inorganic phase is slowly joined in organic facies, stirs 20min, obtained florfenicol compound doxycycline solution prescription of the present invention.
Apply the broiler group of this preparation to a routine ehec infection disease to treat, its cure rate reaches 95%.
The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (6)
1. a preparation technology for florfenicol and compound doxycycline solution, comprises the following steps:
A, the ratio of doxycycline and chelating agent 1:2 ~ 8:1 in mass ratio slowly to be joined in organic solvent;
B, solution steps A obtained are heated to 40 ~ 80 DEG C, and continuous uniform stirs 20 ~ 100 minutes
Slowly add florfenicol in C, the solution that obtains in step B, described florfenicol and doxycycline weight ratio are 1:2 ~ 2:1, are stirred to dissolving, as organic facies;
D, antioxidant, water soluble polymer, solubilizing agent to be added to the water by its weight ratio 0.01% ~ 5% in final mean annual increment solution agent, be stirred to dissolving, as inorganic phase, described antioxidant, water soluble polymer, solubilizing agent part by weight is each other 1:10 ~ 20:10 ~ 80;
E, above-mentioned inorganic phase slowly to be joined in organic facies, stir 20 ~ 60 minutes.
2. the preparation technology of a kind of florfenicol according to claim 1 and compound doxycycline solution, it is characterized in that, the organic solvent in described steps A is the mixture of one or more in dimethyl formamide, dimethyl acetylamide, propylene glycol, ethanol, alpha-pyrrolidone, N-Methyl pyrrolidone, glycerol, ethyl acetate.
3. the preparation technology of a kind of florfenicol according to claim 1 and compound doxycycline solution, it is characterized in that, the antioxidant in described step D is the mixture of one or more in Butylated hydroxyanisole, dibenzylatiooluene, propyl gallate, tertiarybutylhydroquinone, sodium pyrosulfite, sodium sulfite, sodium sulfite, sodium thiosulfate.
4. the preparation technology of a kind of florfenicol according to claim 1 and compound doxycycline solution, is characterized in that, the chelating agent in described steps A is the mixture of one or more in citric acid, EDTA and Quadrafos.
5. the preparation technology of a kind of florfenicol according to claim 1 and compound doxycycline solution, it is characterized in that, the water soluble polymer in described step D is the mixture of one or more in gelatin, polyvinyl alcohol, Polyethylene Glycol, polyvidone.
6. the preparation technology of a kind of florfenicol according to claim 1 and compound doxycycline solution, it is characterized in that, the solubilizing agent in described step D is the mixture of one or more in polysorbate 20, polysorbate 40, polyoxyethylene sorbitan monoleate, polyvidone, polyoxyethylene castor oil.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510427181.0A CN105012320A (en) | 2015-07-20 | 2015-07-20 | Preparation technology for compound solution of florfenicol and doxycycline |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510427181.0A CN105012320A (en) | 2015-07-20 | 2015-07-20 | Preparation technology for compound solution of florfenicol and doxycycline |
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| CN105012320A true CN105012320A (en) | 2015-11-04 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201510427181.0A Pending CN105012320A (en) | 2015-07-20 | 2015-07-20 | Preparation technology for compound solution of florfenicol and doxycycline |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106511355A (en) * | 2016-11-08 | 2017-03-22 | 河南中盛动物药业有限公司 | Florfenicol gel implant for veterinary use and preparation method of florfenicol gel implant |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101502487A (en) * | 2008-12-24 | 2009-08-12 | 天津瑞普生物技术股份有限公司 | Suspension composition containing doxycycline and florfenicol for injection and technique for preparing the same |
| CN102008490A (en) * | 2010-12-07 | 2011-04-13 | 江西新天地药业有限公司 | Compound florfenicol injection for animal |
| CN102973578A (en) * | 2011-09-06 | 2013-03-20 | 菏泽普恩药业有限公司 | Compound preparation used for controlling avian mycoplasma and Escherichia coli mixed infection, and preparation method thereof |
-
2015
- 2015-07-20 CN CN201510427181.0A patent/CN105012320A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101502487A (en) * | 2008-12-24 | 2009-08-12 | 天津瑞普生物技术股份有限公司 | Suspension composition containing doxycycline and florfenicol for injection and technique for preparing the same |
| CN102008490A (en) * | 2010-12-07 | 2011-04-13 | 江西新天地药业有限公司 | Compound florfenicol injection for animal |
| CN102973578A (en) * | 2011-09-06 | 2013-03-20 | 菏泽普恩药业有限公司 | Compound preparation used for controlling avian mycoplasma and Escherichia coli mixed infection, and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 陈卫卫等: "《药剂学》", 31 January 2014, 西安：西安交通大学出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106511355A (en) * | 2016-11-08 | 2017-03-22 | 河南中盛动物药业有限公司 | Florfenicol gel implant for veterinary use and preparation method of florfenicol gel implant |
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