CN102274228B - Compound trimethoprim and sodium succinate florfenicol nanoemulsion preparation and preparation thereof - Google Patents
Compound trimethoprim and sodium succinate florfenicol nanoemulsion preparation and preparation thereof Download PDFInfo
- Publication number
- CN102274228B CN102274228B CN 201110179278 CN201110179278A CN102274228B CN 102274228 B CN102274228 B CN 102274228B CN 201110179278 CN201110179278 CN 201110179278 CN 201110179278 A CN201110179278 A CN 201110179278A CN 102274228 B CN102274228 B CN 102274228B
- Authority
- CN
- China
- Prior art keywords
- trimethoprim
- sodium succinate
- florfenicol
- preparation
- nano
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Abstract
The invention belongs to the technical field of antibacterial veterinary drugs, and in particular relates to a compound trimethoprim and sodium succinate florfenicol nanoemulsion preparation. The nanoemulsion preparation is in an oil-in-water type, has the grain size of between 1nm and 100nm and is prepared from trimethoprim, sodium succinate florfenicol, a surfactant, a cosurfactant, oil and distilled water. The compound trimethoprim and sodium succinate florfenicol nanoemulsion preparation has transparent appearance and can be used for treating various livestock and poultry infections caused by sensitive bacteria.
Description
Technical field
The invention belongs to anti-microbial type veterinary drug technical field, be specifically related to a kind of compound recipe trimethoprim and sodium succinate florfenicol nano-emulsion preparation and preparation method thereof.
Background technology
Antimicrobial drug has advantages such as rapid-action, that production cost is low on the treatment animal infectious disease, make it that application enormous function widely arranged on veterinary clinic.But the limitation of conventional dosage forms and chemical sproof increasing gradually rise and therapeutic effect decline its treatment cost.For this reason, in the clinical practice normal adopt to unite use two or more antibacterials, to reach the expansion antimicrobial spectrum, heighten the effect of a treatment, reduce dosage, reduce or avoid toxic and side effects, reduce or delay the purpose of the generation of Resistant strain.
Trimethoprim (TMP) belongs to synthetic broad spectrum antimicrobicide, is lipotropy weak base, and multiple gram positive bacteria and gram negative bacteria are all had antibacterial action.Single with being prone to produce drug resistance, its drug resistance mechanism possibly be that antibacterial changes metabolic pathway, for example produces more dihydrofolate synthetase, or directly utilizes exogenous folic acid.After antibacterial produces drug resistance, curative effect is reduced, and can cause the propagation of Resistant strain, bring difficulty to treatment.Sodium succinate florfenicol system is the derivant of florfenicol, forms according to the principle design of prodrug, and it all has effect to multiple gram positive bacteria and gram negative bacteria and mycoplasma etc., is broad-spectrum antibacterial medicine, and high concentration has bactericidal action.This medicine clinical drug-resistant phenomenon is serious, and common fastbacteria is gram positive bacteria and gram negative bacterias such as staphylococcus.After antibacterial produces drug resistance, curative effect is reduced, and can cause the propagation of Resistant strain, bring difficulty to treatment.Therefore, how through drug combination and the shortcoming that the exploitation novel form solves trimethoprim and exists more than the sodium succinate florfenicol, improve two medicine clinical application curative effects and become current urgent problem.
Summary of the invention
The object of the present invention is to provide a kind of compound recipe trimethoprim and sodium succinate florfenicol nano-emulsion preparation and preparation method thereof.
The present invention adopts following technical scheme:
A kind of compound recipe trimethoprim and sodium succinate florfenicol nano-emulsion preparation, this nano-emulsion preparation is an oil-in-water type, particle diameter is processed by following weight percentages between 1～100 nm:
Trimethoprim 0.01～1.75%
Sodium succinate florfenicol 0.04～6.99%
Surfactant 21.82～35.69%
Cosurfactant 7.94～11.90%
Oil 3.49～4.76%
Distilled water 47.59～63.54%
The total weight percent of above-mentioned raw materials is 100%.
Described surfactant is tween 80 or castor oil polyoxyethylene; Said cosurfactant is ethanol or 1, the 2-propylene glycol; Said oil is isopropyl myristate or ethyl acetate.
Described surfactant and cosurfactant mass ratio are 2-3:1; Said surfactant and cosurfactant quality sum are 9:1～7:3 with the mass ratio of oil.
A kind of method for preparing compound recipe trimethoprim and sodium succinate florfenicol nano-emulsion preparation specifically may further comprise the steps:
1) gets each raw material in proportion;
2) the trimethoprim crude drug is dissolved in the cosurfactant, adds surfactant and oil phase mixing;
3) the sodium succinate florfenicol is dissolved in the distilled water;
4) solution to the step 2 of dropping step 3) under the room temperature) in the solution of preparation, stir until the system that forms homogeneous transparent, i.e. compound recipe trimethoprim and sodium succinate florfenicol nano-emulsion preparation.
When compound recipe trimethoprim of the present invention and sodium succinate florfenicol nano-emulsion preparation used, every 100kg water added compound recipe trimethoprim of the present invention and sodium succinate florfenicol nano-emulsion preparation 100ml, freely drinks water, and three days is a course of treatment.
The theory of constitution and the scientific basis thereof of compound recipe trimethoprim of the present invention and sodium succinate florfenicol nano-emulsion preparation: because the trimethoprim crude drug is insoluble in water; The sodium succinate florfenicol is soluble in water; Therefore with the aqueous solution of sodium succinate Florfenicol raw material medicine as aqueous portion, with trimethoprim as the oil phase part.
Select for use tween 80 or castor oil polyoxyethylene as surfactant in the raw material of compound recipe trimethoprim of the present invention and sodium succinate florfenicol nano-emulsion preparation; Be because tween 80 and castor oil polyoxyethylene toxicity are less relatively, be not subject to the influence of electrolyte, inorganic salts and soda acid; Select ethanol or 1 for use, the 2-propylene glycol is during as cosurfactant, and the nano-emulsion preparation of formation is not only stable, and as the solvent of trimethoprim, has improved the content of trimethoprim in this compound nanometer emulsion; Isopropyl myristate or ethyl acetate are because the HLB value of isopropyl myristate, ethyl acetate and tween 80 is approaching as oil, are prone to form the stabilized nano breast.
When surfactant and cosurfactant mass ratio were 2-3:1, the nano-emulsion district that the mass ratio of surfactant and cosurfactant sum and oil forms when being 9:1～7:3 was maximum, and the most stable, drug loading is the highest.
Compound recipe trimethoprim of the present invention and sodium succinate florfenicol nano-emulsion preparation appearance transparent; Particle diameter is between 1～100 nm; Its viscosity can add the distilled water adjustment of arbitrary proportion as required; Make things convenient for clinical administration, the structure of two kinds of crude drug trimethoprims and sodium succinate florfenicol does not all change.
Compound recipe trimethoprim of the present invention and sodium succinate florfenicol nano-emulsion preparation can be used for treating poultry by the microbial all kinds of infection of sensitivity.Compared with prior art, compound recipe trimethoprim of the present invention and sodium succinate florfenicol nano-emulsion preparation have the following advantages:
1) safely, efficiently, drug resistance is low;
2) absorb rapidly, bioavailability is high; Targeting drug release, side effect is low; Particle diameter is little and even, the permeable membrane good absorbing;
3) viscosity is low, and pain is little during injection;
4) have good stability, but filtration sterilization is easy to preserve.
The specific embodiment
Embodiment 1
Castor oil polyoxyethylene 9.0g
1,2-propylene glycol 3.0g
Trimethoprim 0.003g
Sodium succinate florfenicol 0.012g
Isopropyl myristate 1.2g
Distilled water 12g
The concrete operations step is:
1) gets each raw material in proportion;
2) the trimethoprim crude drug is dissolved in 1, in the 2-propylene glycol, adds castor oil polyoxyethylene and isopropyl myristate mixing;
3) the sodium succinate florfenicol is dissolved in the distilled water;
4) solution to the step 2 of dropping step 3) under the room temperature) in the solution of preparation, stir until the system that forms homogeneous transparent, promptly particle diameter is the compound recipe trimethoprim and the sodium succinate florfenicol nano-emulsion preparation of 1～100 nm, appearance transparent.
Embodiment 2
Composition of raw materials is following:
Tween 80 3.0g
Ethanol 1.0g
Trimethoprim 0.03 g
Sodium succinate florfenicol 0.12 g
Ethyl acetate 0..44g
Distilled water 8.0g
The concrete operations step is:
1) gets each raw material in proportion;
2) the trimethoprim crude drug is dissolved in the ethanol, adds tween 80 and ethyl acetate mixing;
3) the sodium succinate florfenicol is dissolved in the distilled water;
4) solution to the step 2 of dropping step 3) under the room temperature) in the solution of preparation, stir until the system that forms homogeneous transparent, promptly particle diameter is the compound recipe trimethoprim and the sodium succinate florfenicol nano-emulsion preparation of 1～100 nm, appearance transparent.
Embodiment 3
Composition of raw materials is following:
Tween 80 6.0 g
1,2-propylene glycol 2.0g
Trimethoprim 0.4g
Sodium succinate florfenicol 1.6 g
Isopropyl myristate 0.88g
Distilled water 12 g
The concrete operations step is:
1) gets each raw material in proportion;
2) the trimethoprim crude drug is dissolved in 1, in the 2-propylene glycol, adds tween 80 and isopropyl myristate mixing;
3) the sodium succinate florfenicol is dissolved in the distilled water;
4) solution to the step 2 of dropping step 3) under the room temperature) in the solution of preparation, stir until the system that forms homogeneous transparent, promptly particle diameter is the compound recipe trimethoprim and the sodium succinate florfenicol nano-emulsion preparation of 1～100 nm, appearance transparent.
Embodiment 4
Composition of raw materials is following:
Tween 80 6.0 g
Ethanol 3.0g
Trimethoprim 0.5g
Sodium succinate florfenicol 2.0g
Ethyl acetate 1.0g
Distilled water 15.0 g
The concrete operations step is:
1) gets each raw material in proportion;
2) the trimethoprim crude drug is dissolved in the ethanol, adds tween 80 and ethyl acetate mixing;
3) the sodium succinate florfenicol is dissolved in the distilled water;
4) solution to the step 2 of dropping step 3) under the room temperature) in the solution of preparation, stir until the system that forms homogeneous transparent, promptly particle diameter is the compound recipe trimethoprim and the sodium succinate florfenicol nano-emulsion preparation of 1～100 nm, appearance transparent.
Adopt compound recipe trimethoprim and the sodium succinate florfenicol nano-emulsion preparation of embodiment 1 to carry out following test.
Test 1
Utilize speed that oil-soluble dyes tonyred and water-soluble dye methylene blue spread in compound recipe trimethoprim that embodiment 1 makes and sodium succinate florfenicol nano-emulsion preparation to judge the type of nano-emulsion; Find that methylene blue solution has diffusion in compound recipe trimethoprim that embodiment 1 makes and sodium succinate florfenicol nano-emulsion preparation; Tonyred solution is then not diffusion in compound recipe trimethoprim that embodiment 1 makes and sodium succinate florfenicol nano-emulsion preparation, shows that prepared compound nanometer emulsion is oil-in-water type (O/W).
Test 2Stability test
1) centrifugal acceleration test
Get the compound recipe trimethoprim and the sodium succinate florfenicol nano-emulsion preparation of embodiment 1 preparation, centrifugal with 20 000 r/min, to observe the nanoemulsions outward appearance behind 10 min and still keep clear, the profit lamination does not appear.
2) light stability test
The compound recipe trimethoprim of embodiment 1 preparation and sodium succinate florfenicol nano-emulsion preparation are packed in the vial in right amount, and room temperature placement under (4500 ± 500) the lx illumination condition of sealing back is respectively at 0 d, 5 d, the 10 d observation of taking a sample.The result shows that emulsion keeps the clear outward appearance, does not see phenomenons such as layering and breakdown of emulsion.
3) temperature stability test
The compound recipe trimethoprim and the sodium succinate florfenicol nano-emulsion preparation of embodiment 1 preparation are sub-packed in the vial, and placing respectively after the sealing keeps sample under 4 ℃, 25 ℃, 37 ℃, the 60 ℃ conditions investigates 3 months, whenever observes at a distance from 10 d sampling.The result shows that emulsion all keeps the clear outward appearance under these four kinds of temperature conditions, do not see phenomenons such as layering and breakdown of emulsion.
Test 3The associating drug sensitive test of compound recipe trimethoprim and sodium succinate florfenicol nano-emulsion
1) single medicinal chart sheet is put up a bridge and is tested
The trimethoprim drug sensitive test paper of preparation contains trimethoprim 5 μ g/ sheets, and sodium succinate florfenicol drug sensitive test paper contains trimethoprim 30 μ g/ sheets.Test strain is staphylococcus aureus ATCC
25923With escherichia coli ATCC
25922
With concentration is that the bacterium liquid of 1/2 Maxwell standard opacity tube is inoculated on the MHA culture medium, then each one of above-mentioned two kinds of drug sensitive test paper is attached to the MHA media surface respectively, and spacing 2～3 mm observe antibacterial circle diameter and the form between two scraps of paper after cultivating 18 h for 35 ℃.The result shows that two kinds of antibacterials are to staphylococcus aureus ATCC
25923With escherichia coli ATCC
25922Angle, inhibition zone boundary straight, expression trimethoprim and sodium succinate florfenicol are synergetic antibacterial effect.
2) meat soup dilution chessboard test
According to measured single medicine trimethoprim and sodium succinate florfenicol nano-emulsion to staphylococcus aureus ATCC
25923With escherichia coli ATCC
25922Minimum inhibitory concentration MIC value, adopt micro-meat soup dilution chessboard method to carry out the associating antibacterial tests of medicine.
Adopt the compound recipe trimethoprim and the sodium succinate florfenicol nano-emulsion preparation of embodiment 1 preparation; Become a series of concentration with the MHB doubling dilution respectively; Two kinds of antibacterials with variable concentrations design by chessboard method then; Combination in twos adds in the 96 hole flat boards, and every kind of antibacterials are got 50 μ L, again with 1.5 * 10
5The bacterium liquid 100 μ L of CFU/mL add in the hand-hole, hatch 24 h for 37 ℃.Separately MIC when MIC when writing down two prescriptions and solely using and two medicine drug combinations, and calculate the FIC index.Process of the test repeats 5 times, and getting mode is the MIC value, and the result sees table 1.
Table 1 is the MIC (mg/L) and the FIC index of trimethoprim and sodium succinate florfenicol list usefulness and coupling:
Table 1
Can know that by table 1 trimethoprim and sodium succinate florfenicol are to staphylococcus aureus ATCC
25923MIC during coupling is 1/16 and 1/4 times of single time spent, to escherichia coli ATCC
25922MIC during coupling all is 1/8 times for single time spent, and the two coupling is to staphylococcus aureus ATCC
25923With escherichia coli ATCC
25922The FIC index all be not more than 0.5.Results suggest; Compound recipe trimethoprim of the present invention and sodium succinate florfenicol nano-emulsion preparation can improve the antibacterial activity of trimethoprim and sodium succinate florfenicol, medicament curative effect enhancement, thus can reduce dosage; Reduce drug residue, delay or reduce bacterial resistance.
Claims (3)
1. compound recipe trimethoprim and sodium succinate florfenicol nano-emulsion preparation is characterized in that this nano-emulsion preparation is an oil-in-water type, and particle diameter is processed by following weight percentages between 1～100 nm:
Described surfactant is tween 80 or castor oil polyoxyethylene; Said cosurfactant is ethanol or 1, the 2-propylene glycol; Said oil is isopropyl myristate or ethyl acetate.
2. compound recipe trimethoprim as claimed in claim 1 and sodium succinate florfenicol nano-emulsion preparation is characterized in that: described surfactant and cosurfactant mass ratio are 2-3:1; Said surfactant and cosurfactant quality sum are 9:1～7:3 with the mass ratio of oil.
3. a method for preparing described compound recipe trimethoprim of claim 1 and sodium succinate florfenicol nano-emulsion preparation is characterized in that, specifically may further comprise the steps:
1) gets each raw material in proportion;
2) the trimethoprim crude drug is dissolved in the cosurfactant, adds surfactant and oil phase mixing;
3) the sodium succinate florfenicol is dissolved in the distilled water;
4) solution to the step 2 of dropping step 3) under the room temperature) in the solution of preparation, stir until the system that forms homogeneous transparent, i.e. compound recipe trimethoprim and sodium succinate florfenicol nano-emulsion preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110179278 CN102274228B (en) | 2011-06-29 | 2011-06-29 | Compound trimethoprim and sodium succinate florfenicol nanoemulsion preparation and preparation thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110179278 CN102274228B (en) | 2011-06-29 | 2011-06-29 | Compound trimethoprim and sodium succinate florfenicol nanoemulsion preparation and preparation thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102274228A CN102274228A (en) | 2011-12-14 |
| CN102274228B true CN102274228B (en) | 2012-09-05 |
Family
ID=45100175
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110179278 Expired - Fee Related CN102274228B (en) | 2011-06-29 | 2011-06-29 | Compound trimethoprim and sodium succinate florfenicol nanoemulsion preparation and preparation thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102274228B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103705528A (en) * | 2013-12-26 | 2014-04-09 | 南阳新先锋制药有限公司 | Compound colinflosaxin soluble powder for preventing and treating poultry colibacillosis |
| CN105012304B (en) * | 2015-07-08 | 2018-12-11 | 河南牧业经济学院 | A kind of compound florfenicol composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101653441A (en) * | 2009-09-24 | 2010-02-24 | 陈建波 | Veterinary compound florfenicol injection and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102028691A (en) * | 2010-12-08 | 2011-04-27 | 纽素乐必佳（天津）药业集团有限公司 | Composite florfenicol injection for livestock and preparation method thereof |
-
2011
- 2011-06-29 CN CN 201110179278 patent/CN102274228B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101653441A (en) * | 2009-09-24 | 2010-02-24 | 陈建波 | Veterinary compound florfenicol injection and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102274228A (en) | 2011-12-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101744763B (en) | Enrofloxacin nano emulsion and method for preparing same | |
| CN101422432B (en) | Preparation method of tilmicosin nano-emulsion antibacterial drug | |
| Dong et al. | Preparation and in vitro, in vivo evaluations of norfloxacin-loaded solid lipid nanopartices for oral delivery | |
| CN102440996A (en) | Compound albendazole suspension containing ivermectin nanoemulsion and preparation method thereof | |
| Omran et al. | Evaluation of antimicrobial activity of Triphala constituents and nanoformulation | |
| Zhu et al. | Evaluation of the antibacterial activity of tilmicosin-SLN against Streptococcus agalactiae: in vitro and in vivo studies | |
| CN102525919A (en) | Decoquinate nanoemulsion coccidium-resisting drug and preparation method thereof | |
| Chen et al. | Preparation and evaluation of tilmicosin-loaded hydrogenated castor oil nanoparticle suspensions of different particle sizes | |
| CN102274228B (en) | Compound trimethoprim and sodium succinate florfenicol nanoemulsion preparation and preparation thereof | |
| CN104352566A (en) | Oil-in-water compound chlortetracycline nanoemulsion | |
| CN102228432A (en) | Ofloxacin nanoemulsion antibacterial medicine and preparation method thereof | |
| Pal et al. | Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect | |
| CN102895245A (en) | Compound trimethoprim and doxycycline hydrochloride nanoemulsion preparation and preparation method thereof | |
| CN102657610A (en) | 3,5-dihydroxyl4-isopropyl diphenylethylene micro-emulsion and preparation method thereof | |
| CN102274179A (en) | Mequindox nanoemulsion antibacterial medicament and preparation method thereof | |
| CN102283842A (en) | Compound mequindox florfenicol nanoemulsion antibacterial drug and preparation method thereof | |
| CN104274826B (en) | A kind of oil-in-water type compound colistin nano-emulsion | |
| Lashkenari et al. | In vitro antiprotozoal activity of poly (rhodanine)-coated zinc oxide nanoparticles against Trichomonas gallinae | |
| CN104706636A (en) | Albendazole preparation and preparation method thereof | |
| CN102499935B (en) | Compound spiramycin nanoemulsion oral liquid and preparation method thereof | |
| CN106176605A (en) | A kind of method using non-polar support to prepare florfenicol submicron emulsion | |
| CN103417554B (en) | A kind of antitumor medicine composition and its application | |
| CN104367989A (en) | Oil-in-water type neomycin sulfate nosiheptide nanoemulsion antimicrobial medicine | |
| CN102327273B (en) | Compound clobetasol propionate nano-medicament and preparation method thereof | |
| CN102657609A (en) | Sulfadoxine composite nanoemulsion antibacterial medicine and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120905 Termination date: 20150629 |
|
| EXPY | Termination of patent right or utility model |