CN102488709A - Florfenicol-zinc chelate injection and preparation method thereof - Google Patents
Florfenicol-zinc chelate injection and preparation method thereof Download PDFInfo
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- CN102488709A CN102488709A CN2011104495809A CN201110449580A CN102488709A CN 102488709 A CN102488709 A CN 102488709A CN 2011104495809 A CN2011104495809 A CN 2011104495809A CN 201110449580 A CN201110449580 A CN 201110449580A CN 102488709 A CN102488709 A CN 102488709A
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- florfenicol
- zinc
- injection
- chelates
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Abstract
The invention discloses a florfenicol-zinc chelate injection and a preparation method thereof. The injection comprises components of, by weight: 10-50 parts of florfenicol, 1-5 parts of zinc salt, 15-65 parts of an amide solvent, and 10-65 parts of an auxiliary solvent. The preparation method of the florfenicol-zinc chelate injection comprises steps that: the amide solvent with the above weight proportion and approximately 80-95% of the auxiliary solvent are mixed with the zinc salt; the mixture is heated to a temperature of 65-75 DEG C, and the temperature is maintained for 1.5-2.5h; florfenicol is dissolved in the mixed solution; rest of the auxiliary solvent is added to the mixed solution; the solution is filtered by using a sand-core filter stick; an obtained clarified solution is encapsulated, and is subject to Arnold steam sterilizing under a temperature of 115 DEG C. The injection provided by the invention is advantaged in good syringeability, good physical stability and good chemical stability. Compared to a florfenicol injection solution that does not contain zinc, the antibiotic function of the injection provided by the invention is higher. The dosage of florfenicol can be reduced, such that the generation of bacteria drug resistance can be reduced. The injection and the method satisfy the requirements of animal-use product and food safety.
Description
Technical field
The invention belongs to the veterinary and use medicine field, be specially a kind of florfenicol chelates of zinc injection that is used to treat poultry sensitivity bacterial infection and preparation method thereof.
Background technology
Florfenicol (Florfenico1) has another name called Florfenicol, fluorinated chloramphenicol, and chemical name is (R-(R*, R*))-2,2-two chloro-N-(1-(methyl fluoride)-2-hydroxyl-2-(4-(sulfonyloxy methyl) phenyl) ethyl) acetamide.Florfenicol is the animal specific broad spectrum antibiotic that U.S. Schering-Plough company developed at the end of the seventies in last century; Be characterized in has a broad antifungal spectrum, absorb in good, the body and distribute extensively; Fowl bacterial disease therapeuticing effect for due to the sensitive organism is remarkable; Particularly do not have potential induced aplastic anemia effect, do not have teratogenesis, carcinogenic and mutagenic action yet.Florfenicol more than 20 country's listings, because chloromycetin has the untoward reaction of serious induced aplastic anemia, has forbidden being used for food animal at present; Therefore; On animal diseases control, food animal especially, florfenicol has broad application prospects.Florfenicol is mainly used in the cattle respiratory disease that treatment pasteurella and haemophilus cause as the animal specific medicine; The cattle foot rot that Fusobacterium is caused has better curative effect; Also be used for pig, chicken infectious disease due to the sensitive organism, like pig contagious infection property pleuropneumonia etc.
Existing florfenicol dosage form has injection, pre-mixing agent, powder etc.Other reports that there is the florfenicol implant in the U.S., is used to treat cattle respiratory disease.The domestic finding dosage form of China has injection, powder etc., also has about the research of florfenicol liposome and the report of aqueous suspensoid injectio.About the patent of florfenicol preparation, except that powder, see with non-water-soluble matchmaker's injection and suspending agent more.Like number of patent application is that the Chinese invention patent application of CN200710300061.X discloses long acting florfenicol oleo-injection and preparation method thereof; Patent CN91108502.54 discloses pharmaceutical composition of florfenicol.Number of patent application is that the Chinese invention patent application of CN200810220327.4 discloses a kind of suspension emulsion of florfenicol; Number of patent application is that the Chinese invention patent application of CN200480021905.13 discloses the veterinary aqueous injectable suspensions that contains florfenicol.Not seeing at present has florfenicol and chelates of zinc to prepare the injection technical patent.
Zinc is the indispensable nutrient of body, and body includes the 2-3 gram, all contains zinc in the tens of kinds of enzymes relevant with organism metabolism, acts on very extensive.Obstacle appears in nucleic acid and protein synthesis during zinc deficiency, the synthetic and secretion minimizing of growth hormone, and hypoevolutism, of short and small stature, the sexual organ development is incomplete.It is normal that zinc can be kept cutaneomucosal tissue.The metallic zinc ion has sterilizing function.Antibacterial is electronegative, and zinc ion tool positive charge, therefore, the adsorbable antibacterial of zinc ion also penetrates bacteria cell wall, and it is synthetic to destroy bacterium protein, thereby plays antibacterial effect.Zinc ion can strengthen antibiotic antibacterial action, often antibiotic is processed zinc salt, like bacitracin zinc, Zn-PPA, zinc sulfadiazine etc.Antibacterial is ubiquitous, from the serious health that has threatened humans and animals of the infection of malignant bacteria.In recent years because the particularly antibiotic a large amount of uses of medicine, the continuous appearance of drug-resistance of bacteria problem and residue of veterinary drug problem.
The utility model content
The objective of the invention is deficiency, a kind of florfenicol chelates of zinc injection that can strengthen the florfenicol antibacterial action is provided to the above prior art existence.
Another object of the present invention provides a kind of method for preparing of florfenicol chelates of zinc injection.
For achieving the above object, technical scheme of the present invention is: florfenicol chelates of zinc injection comprises following compositions in weight portion:
Florfenicol 10-50,
Zinc salt 1-5,
Amide solvent 15-65,
Secondary solvent 10-65,
The preferred parts by weight of said florfenicol are 20-40.
The preferred parts by weight of said zinc salt are 2-3.
Said zinc salt can be zinc oxide, zinc sulfate, zinc chloride or zinc acetate etc., preferred zinc oxide.
Said amide solvent comprises N, N---dimethyl formamide and N, N---dimethyl acetylamide.Amide solvent is selected a kind of getting final product wherein for use.
Said secondary solvent is propylene glycol or glycerin, preferred propylene glycol.
The method for preparing of florfenicol chelates of zinc injection; It step that comprises is: the amide solvent of above-mentioned parts by weight, the secondary solvent of about 80-95% volume are mixed with zinc salt, be warmed up to 65-75 ℃ and kept 1.5-2.5 hour, then florfenicol is dissolved in the said mixed solution; Add remaining secondary solvent; Filter through the core filter stick, the embedding of gained settled solution is after 115 ℃ of flowing steam sterilizations can make florfenicol injection of the present invention.
Compared with prior art, the present invention has following advantage: the novel florfenicol injection that the present invention makes has good syringeability, physics and chemical stability; And, owing to contain zinc in this injection, stronger than not zinciferous florfenicol injection antibacterial action.Through adopting chessboard method; The florfenicol injection (containing zinc salt) that mensuration florfenicol injection (not containing zinc salt) and the present invention make shows the result of the test of escherichia coli 078 antibacterial activity in vitro: florfenicol injection (not containing zinc salt) is 0.64mg/L to escherichia coli 078 minimal inhibitory concentration (MIC), and part escherichia coli 078 are to its drug resistance.The florfenicol injection that the present invention makes (containing zinc salt) is to escherichia coli 078 minimal inhibitory concentration (MIC) 0.16mg/L.Florfenicol chelates of zinc injection of the present invention can reduce the consumption of florfenicol, reduces the generation of bacterial drug resistance, meets the requirement of animal specific and food safety.
The specific embodiment
The following example has been set forth the present invention in detail, under the prerequisite that does not depart from purpose disclosed by the invention and intention, can carry out various improvement.
Embodiment 1
Florfenicol chelates of zinc injection comprises following compositions in weight portion:
Florfenicol 10,
Zinc salt 1,
Amide solvent 15,
Secondary solvent 10.
Embodiment 2
Florfenicol chelates of zinc injection comprises following compositions in weight portion:
Florfenicol 50,
Zinc salt 5,
Amide solvent 65,
Secondary solvent 65.
Embodiment 3
Florfenicol chelates of zinc injection comprises following compositions in weight portion:
Florfenicol 20-40,
Zinc salt 2-3,
Amide solvent 15-65,
Secondary solvent 10-65,
Said zinc salt can be zinc oxide, zinc sulfate, zinc chloride or zinc acetate etc., preferred zinc oxide.
Said amide solvent comprises N, N---dimethyl formamide and N, N---dimethyl acetylamide.Amide solvent is selected a kind of getting final product wherein for use.
Said secondary solvent is propylene glycol or glycerin, preferred propylene glycol.
The method for preparing of florfenicol chelates of zinc injection, it step that comprises is: with the N of above-mentioned parts by weight, N---dimethyl formamide, 80-95% volume secondary solvent mix with zinc salt; Be warmed up to about 70 ℃ and kept 2 hours; Then florfenicol is dissolved in this solution, and, filters through the core filter stick with remaining secondary solvent adjustment volume; The embedding of gained settled solution is after 115 ℃ of flowing steam sterilizations can make florfenicol injection of the present invention.
Embodiment 4
Florfenicol chelates of zinc injection comprises following component:
Florfenicol 10,
Zinc oxide 2.5,
N, N---dimethyl formamide 25,
Propylene glycol adds to 100mL;
The method for preparing of said florfenicol chelates of zinc injection, the step that comprises is following: the N of above-mentioned parts by weight, N---dimethyl formamide, about 90% propylene glycol mix with zinc salt; Be warmed up to about 70 ℃ and kept 2 hours; Then florfenicol is dissolved in this solution, and, filters through the core filter stick with remaining propylene glycol adjustment volume; The embedding of gained settled solution is after 115 ℃ of flowing steam sterilizations can make florfenicol injection of the present invention.
Embodiment 5
Florfenicol chelates of zinc injection comprises following component:
Florfenicol 30g,
Zinc oxide 5g,
N, N---dimethyl formamide 39g,
Propylene glycol adds to 100mL.
The method for preparing of said florfenicol chelates of zinc injection, the step that comprises is following: with above-mentioned N, N---dimethyl formamide, about 90% propylene glycol mix with zinc salt; Be warmed up to about 70 ℃ and kept 2 hours; Then florfenicol is dissolved in this solution, and, filters through the core filter stick with remaining propylene glycol adjustment volume; The embedding of gained settled solution is after 115 ℃ of flowing steam sterilizations can make florfenicol injection of the present invention.
Embodiment 6
Florfenicol chelates of zinc injection comprises following component:
Florfenicol 30g,
Zinc acetate 7.5g,
N, N---dimethyl acetylamide 35g,
Propylene glycol adds to 100mL.
The method for preparing of said florfenicol chelates of zinc injection, the step that comprises is following: with above-mentioned N, N---dimethyl acetylamide, about 90% propylene glycol mix with zinc salt; Be warmed up to about 70 ℃ and kept 2 hours; Then florfenicol is dissolved in this solution, and, filters through the core filter stick with remaining propylene glycol adjustment volume; The embedding of gained settled solution is after 115 ℃ of flowing steam sterilizations can make florfenicol injection of the present invention.
In order to verify the drug effect of florfenicol chelates of zinc injection, we have carried out the clinical efficacy test of this medicine to porcine contagious pleuropneumonia.
In March, 2010-JIUYUE, in overseas Chinese farm pig farm, suburb, Sihui City, Guangdong Province, select 20-30 kilogram natural infection contagious pleuropneumonia Actinobacillus and sick pig through making a definite diagnosis.Kind: long white big cross-bred pig, without any Drug therapy.
Diagnostic criteria: the pig sudden onset, fervescence (41～42 ℃), heart rate increases, dyspnea, quickening or ventral breathing, cough, spirit is depressed, and appetite is useless exhausted.The sick pig of typical case is cutd open visceral pleura fiber disposition gangrenosum acne and hemorrhagic pneumonia, the fibroid pleuritis of inspection visible features property.Lung and pleural adhesion, lung is aubergine, and necrosis region, cheesy focus and cavity etc. are arranged.
1 trial drug
Florfenicol chelates of zinc injection, specification: 5ml: florfenicol 1.5g, prepare injection by following component:
Florfenicol 30g (weight/volume)
Zinc oxide 5g (weight/volume)
N, N---dimethyl formamide 39g (weight/volume)
Propylene glycol adds to 100ml (weight/volume)
Method for preparing does; Amide solvent, about 90% secondary solvent are mixed with zinc salt, be warmed up to 70 ℃ and kept 2 hours, then florfenicol is dissolved in this solution; And with remaining secondary solvent adjustment volume; Filter through the core filter stick, the embedding of gained settled solution is after 115 ℃ of flowing steam sterilizations can make florfenicol injection of the present invention.
2 contrast medicines
Florfenicol injection, prepare injection by following component:
Florfenicol 30g (weight/volume)
N, N---dimethyl formamide 39g (weight/volume)
Propylene glycol adds to 100ml (weight/volume)
Florfenicol injection is except that oxygen-free zinc, and all the other compositions are the same with florfenicol chelates of zinc injection with compound method.
3 tests are divided into groups
The trial drug group: florfenicol chelates of zinc injection, by per 1 kg body weight intramuscular injection 0.1ml, medication in per 48 hours once, logotype 2 times.The drug withdrawal continued was observed 3 days.
The medicine matched group: florfenicol injection, per 1 kg body weight intramuscular injection 0.1ml, medication in per 48 hours once, logotype 2 times.The drug withdrawal continued was observed 3 days.
Ill not administration matched group: do not give any Drug therapy, the clinical symptoms change of suffering from pig is carried out observed and recorded.
4 curative effect judging standards
Invalid: drug administration by injection is the commentaries on classics of not getting better of symptoms such as test pig spirit, body temperature, appetite, breathing after 3 days, even worsens and death occurs.
Inefficiency: the percentage calculation inefficiency that accounts for this group test number according to invalid number.
Effectively: test pig appetite increases drug administration by injection after 3 days, the mental status takes an evident turn for the better, has slight ventral breathing or cough.
Total effective rate: effective number is total effective number with curing a number sum, accounts for the percentage calculation total effective rate of this group test number according to total effective number.
Cure: drug administration by injection after 3 days the test pig mental status, appetite, breathing, body temperature each side all recover normally, do not have after the drug withdrawal and recur.
Cure rate: the percentage calculation cure rate that accounts for this group number according to a healing number.
5 result of the tests
Florfenicol chelates of zinc injection is to the clinical treatment comparative test result of porcine contagious pleuropneumonia
6 results
Adopt Radit method statistical analysis.
(1) pig of ill not administration matched group is through observing, and symptom has no significant change or increases the weight of even death in 5 days, promptly takes treatment to handle for reducing the loss.
(2) test group florfenicol chelates of zinc injection is 80.0% to the cure rate of porcine contagious pleuropneumonia, and total effective rate is: 96.67%.The cure rate of florfenicol injection matched group is 60.0%, and total effective rate is 76.67%.
(3) statistical results show: florfenicol chelates of zinc injection drug test group, florfenicol injection matched group, with ill not administration matched group relatively; Its cure rate, total effective rate difference is (P＜0.01) extremely significantly, explains that florfenicol chelates of zinc injection, florfenicol injection are all effective in cure to porcine contagious pleuropneumonia.
(4) florfenicol chelates of zinc injection drug test group and florfenicol injection matched group are relatively; Its cure rate, total effective rate difference is (P＜0.01) extremely significantly, and florfenicol chelates of zinc injection all is significantly higher than florfenicol injection at cure rate, effective percentage.
(5) result of the test shows, though florfenicol chelates of zinc injection, florfenicol injection are all effective in cure to porcine contagious pleuropneumonia, the general curative effect of florfenicol chelates of zinc injection drug test group significantly is superior to florfenicol injection.And the florfenicol chelates of zinc injection that the embodiment of the invention obtains all has similar effect.
The foregoing description is not to be limitation of the present invention; The those of ordinary skill in relevant technologies field; Under the situation that does not break away from the spirit and scope of the present invention; Can also make various variations and modification, so all technical schemes that are equal to also should belong to category of the present invention, scope of patent protection of the present invention should be limited each claim.
Claims (7)
1. florfenicol chelates of zinc injection is characterized in that, processes to comprise following compositions in weight portion:
Florfenicol 10-50,
Zinc salt 1-5,
Amide solvent 15-65,
Secondary solvent 10-65.
2. florfenicol chelates of zinc injection according to claim 1 is characterized in that the parts by weight of said florfenicol are 20-40.
3. florfenicol chelates of zinc injection according to claim 1 is characterized in that the parts by weight of said zinc salt are 2-3.
4. florfenicol chelates of zinc injection according to claim 3 is characterized in that said zinc salt is zinc oxide, zinc sulfate, zinc chloride or zinc acetate.
5. florfenicol chelates of zinc injection according to claim 1 is characterized in that said amide solvent comprises N, N---dimethyl formamide and N, N---dimethyl acetylamide.
6. florfenicol chelates of zinc injection according to claim 1 is characterized in that said secondary solvent is propylene glycol or glycerin.
7. according to the method for preparing of the arbitrary described florfenicol chelates of zinc injection of claim 1-6; It is characterized in that the step that comprises is: the amide solvent of above-mentioned parts by weight, the secondary solvent of 80-95% are mixed with zinc salt, be warmed up to 65-75 ℃ and kept 1.5-2.5 hour; Then florfenicol is dissolved in the said mixed solution; Add remaining secondary solvent, filter, sterilize after the embedding of gained settled solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110449580 CN102488709B (en) | 2011-12-28 | 2011-12-28 | Florfenicol-zinc chelate injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110449580 CN102488709B (en) | 2011-12-28 | 2011-12-28 | Florfenicol-zinc chelate injection and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
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| CN102488709A true CN102488709A (en) | 2012-06-13 |
| CN102488709B CN102488709B (en) | 2013-10-30 |
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| CN 201110449580 Expired - Fee Related CN102488709B (en) | 2011-12-28 | 2011-12-28 | Florfenicol-zinc chelate injection and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973498A (en) * | 2012-12-13 | 2013-03-20 | 江苏恒丰强生物技术有限公司 | Florfenicol injection and preparation method thereof |
| CN104188901A (en) * | 2014-08-12 | 2014-12-10 | 河南迪冉生物科技有限公司 | Florfenicol injection for livestock and preparation method thereof |
| CN112641954A (en) * | 2020-12-30 | 2021-04-13 | 广东三水正大康畜牧发展有限公司 | Water-soluble florfenicol clathrate compound, simple molecular coating method thereof and prepared solid preparation |
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| US6162446A (en) * | 1998-03-11 | 2000-12-19 | Arch Chemicals, Inc. | In-situ generation of zinc pyrithione in personal care compositions |
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| CN101422464A (en) * | 2007-10-31 | 2009-05-06 | 天津生机集团有限公司 | Compound fubennikao injection |
| CN102161693A (en) * | 2010-12-27 | 2011-08-24 | 江苏九阳生物制药有限公司 | Preparation method of zinc bacitracin |
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2011
- 2011-12-28 CN CN 201110449580 patent/CN102488709B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6162446A (en) * | 1998-03-11 | 2000-12-19 | Arch Chemicals, Inc. | In-situ generation of zinc pyrithione in personal care compositions |
| CN1519227A (en) * | 2003-01-22 | 2004-08-11 | 琼 吴 | Zine chelated amino acid as well as its preparation and application |
| CN101422464A (en) * | 2007-10-31 | 2009-05-06 | 天津生机集团有限公司 | Compound fubennikao injection |
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Non-Patent Citations (1)
| Title |
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| 周立华等: "《氯霉素锌霜的制备与质量控制》", 《中国现代药物应用》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973498A (en) * | 2012-12-13 | 2013-03-20 | 江苏恒丰强生物技术有限公司 | Florfenicol injection and preparation method thereof |
| CN104188901A (en) * | 2014-08-12 | 2014-12-10 | 河南迪冉生物科技有限公司 | Florfenicol injection for livestock and preparation method thereof |
| CN112641954A (en) * | 2020-12-30 | 2021-04-13 | 广东三水正大康畜牧发展有限公司 | Water-soluble florfenicol clathrate compound, simple molecular coating method thereof and prepared solid preparation |
| CN112641954B (en) * | 2020-12-30 | 2023-07-04 | 广东正大康生物科技股份有限公司 | Water-soluble florfenicol compound and simple molecular coating method thereof, and prepared solid preparation |
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| CN102488709B (en) | 2013-10-30 |
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