CN106236705A - A kind of florfenicol solution agent that can be used for drinking water administration and preparation method thereof - Google Patents
A kind of florfenicol solution agent that can be used for drinking water administration and preparation method thereof Download PDFInfo
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- CN106236705A CN106236705A CN201610768292.2A CN201610768292A CN106236705A CN 106236705 A CN106236705 A CN 106236705A CN 201610768292 A CN201610768292 A CN 201610768292A CN 106236705 A CN106236705 A CN 106236705A
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- florfenicol
- solution agent
- magnesium chloride
- polyethylene glycol
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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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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- 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
- A61K47/02—Inorganic compounds
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- 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
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- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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- 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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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Abstract
The invention discloses a kind of florfenicol solution agent and preparation method thereof, described florfenicol solution agent is made up of florfenicol, N, N dimethylformamide, polyethylene glycol 200, glycerin methylal, magnesium chloride.This solvent preparation is: takes N, N dimethylformamide and is warming up to 70 DEG C, adds florfenicol, and stirring, to dissolving, adds glycerin methylal and magnesium chloride, stirs；Being eventually adding polyethylene glycol 200 and be settled to 100 milliliters, stirring is the most molten clearly.Using the florfenicol solution prepared of this method can be the most soluble in water, this florfenicol solution stability be high, dispersion of medicine, can arbitrary proportion miscible with water.After drinking water administration, reduce the stress of poultry in administration process, bacterial disease of fowl can be treated more fast and effectively.
Description
Technical field
The present invention relates to a kind of florfenicol formulations preparation field, particularly to a kind of florfenicol solution agent and preparation thereof
Method, belongs to veterinary drug technical field.
Background technology
Florfenicol (florfenicol), also known as Florfenicol, is that Schering Plough company of the U.S. was developed in 1988
A kind of Novel veterinarian special chloromycetin broad spectrum antibiotic of merit, belongs to one of 4 kinds of antibacterial that U.S. FDA certification passes through.Its
Chemical name be D (+)-Soviet Union-1-to methylsulfonyl phenyl-2-dichloro acetamino-3-fluorine propanol.It has has a broad antifungal spectrum, absorption
Well, the feature such as distribution in vivo is wide, safe and efficient, drug resistance incidence rate is low, the fowl bacterial disease caused by sensitive organism is controlled
Therapeutic effect is notable.
Florfenicol is the most conventional a kind of veterinary antibiotic, and has a broad antifungal spectrum, to Salmonella, escherichia coli, deformation
Bacillus, haemophilus, Actinobacillus pleuropneumoniae, mycoplasma hyopneumoniae, Streptococcus suis, pig pasteurellosis bacillus, bronchus deteriorated blood are won
Family name bacillus, staphylococcus aureus etc. are the most sensitive；Bacteriostasis is strong, and minimal inhibitory concentration (MIC) is low, and antibacterial effect is that chlorine is mould
Element, 15-20 times of thiamphenicol；This medicine is prone to absorb, the most widely distributed, and feedstuff is administered latter 60 minutes, organizes Chinese medicine
Substrate concentration can peaking, can rapid symptom management；Safety is high, nontoxic, noresidue, hidden without potential induced aplastic anemia
Suffer from, be suitable for the large-scale plant of scale and use.Additionally, moderate, prevent and treat the most safe wonderful bacterium of medicine of respiratory tract disease than other
Element (Tiamulin), tilmicosin, azithromycin etc. are all cheap, and drug cost is prone to accept for user.Owing to having these features,
Domestic florfenicol is used widely, and becomes current preventing and treating livestock and poultry respiratory and the drug of first choice of digestive tract bacterial infection disease
Thing.
At present, florfenicol is mainly used in bacterial disease of fowl, as bacillary respiratory system disease, colibacillosis,
Pasteurellosis bacillus and other intestinal infections etc..Especially evident in efficacy to respiratory system infection and intestinal infection, abroad it is additionally operable to treatment
Birds bacillus bipolaris septicus infects.Use by recommended amounts and have no side effect, animal and food will not be worked the mischief.Put into practice table
Bright florfenicol is the medicine that in poultry, antibacterial effect is best.
In recent years, the invasion and attack of various bacterial diseasees, cause bigger harm, some the most conventional chemical drugs to poultry husbandry
Oneself produces drug resistance to thing mostly, and clinical disease lacks effectively treatment.On poultry clinical treatment, due to poultry quantity
Many, dosage is big, drug administration by injection, inconvenient operation, and the stress causing poultry is big, so using drinking water administration, energy
Treat bacterial disease of fowl more fast and effectively.But the water solublity of florfenicol is excessively poor, even making solution
Agent, is used clinically for drinking water administration, because the characteristic that florfenicol is hydrophobic, also can separate out, block water fountain, and restrict its
Application in actual production.
Summary of the invention
It is an object of the invention to avoid the deficiency in florfenicol clinical practice, it is provided that the fluorobenzene for animals of a kind of solvable water
Buddhist nun examines solution.
The present invention utilizes the different ratio of solvent and the use of solubilizing agent, solves the deliquescent problem of florfenicol.
The present invention adds solubilizing agent, solves florfenicol and meets the technical barrier that elutriation goes out.
The formula of the present invention adds antioxidant, it is ensured that the stability of solution, solve its solution instability
Technical barrier.
It is an object of the invention to the defect existed for existing florfenicol, applicant of the present invention has carried out improvement and has ground
Study carefully, it is provided that a kind of florfenicol solution and production method thereof, it is possible to and water is with arbitrary proportion dissolving, increases its convenience, reduces
The stress of poultry in administration process, and then improve the bioavailability of medicine.
Described a kind of florfenicol solution agent that can be used for drinking water administration, by florfenicol, DMF, gathers
Ethylene glycol-200, glycerin methylal, magnesium chloride form.
Containing florfenicol 5～30g in described every 100ml florfenicol solution agent, DMF 10～25ml,
Glycerin methylal 5～20ml, magnesium chloride 5～7g, surplus is polyethylene glycol 200；
During preferably florfenicol solution agent prescription is: florfenicol 15g, DMF 20ml, glycerol first contracts
Aldehyde 14ml, magnesium chloride 6g, surplus is polyethylene glycol 200.
(1) taking recipe quantity DMF and be warming up to 70 DEG C, add florfenicol, stirring is extremely dissolved,
(2) above-mentioned solution adds recipe quantity glycerin methylal and magnesium chloride, stir；
(3) it is eventually adding Polyethylene Glycol-200 and is settled to recipe quantity, stir to clarify.
Products obtained therefrom is carried out fill, sterilizing, convenient storage and transport.
The invention has the beneficial effects as follows:
The invention provides a kind of florfenicol solution agent preparation method, solve the shortcoming that florfenicol water soluble is poor,
The product stability that produced is high, dispersion of medicine, can arbitrary proportion miscible with water, and technique is simple, it is easy to industry metaplasia
Produce.And florfenicol solution preparation uses drinking water administration, can treat bacterial disease of fowl more fast and effectively.
Below by detailed description of the invention, the present invention is described in further details, but is not the limit to the present invention
System, according to the foregoing of the present invention, according to ordinary technical knowledge and the customary means of this area, above-mentioned without departing from the present invention
Under basic fundamental thought premise, it is also possible to make the amendment of other various ways, replace or change.
Detailed description of the invention
For making the object, technical solutions and advantages of the present invention clearer, make further below in conjunction with embodiment
Describe in detail.
Embodiment 1
In every 1000ml solution, containing florfenicol 150g, DMF 200ml, Polyethylene Glycol-200 is about
450ml, glycerin methylal 140ml, magnesium chloride 60g
The preparation method of the florfenicol solution of the present embodiment, comprises the following steps:
(1) taking DMF 200ml and be warming up to 70 DEG C, add florfenicol 150g, stirring is extremely dissolved,
(2) add glycerin methylal 140ml and magnesium chloride 60g, stir；
(3) it is eventually adding Polyethylene Glycol-200 and is settled to 1000ml, stir to clarify.
Products obtained therefrom is carried out fill, sterilizing, convenient storage and transport.
Embodiment 2
In every 1000ml solution, containing florfenicol 150g, DMF 150ml, Polyethylene Glycol-200 is about
430ml, glycerin methylal 200ml, magnesium chloride 70g
The preparation method of the florfenicol solution of the present embodiment, comprises the following steps:
(2) take DMF 150ml and be warming up to 70 DEG C, add florfenicol 150g, stirring is extremely dissolved,
(2) add glycerin methylal 200ml and magnesium chloride 70g, stir；
(3) it is eventually adding Polyethylene Glycol-200 and is settled to 1000ml, stir to clarify.
Products obtained therefrom is carried out fill, sterilizing, convenient storage and transport.
Embodiment 3
In every 1000ml solution, containing florfenicol 300g, DMF 250ml, Polyethylene Glycol-200 is about
300ml, glycerin methylal 100ml, magnesium chloride 50g
The preparation method of the florfenicol solution of the present embodiment, comprises the following steps:
(3) take DMF 250ml and be warming up to 70 DEG C, add florfenicol 300g, stirring is extremely dissolved,
(2) add glycerin methylal 100ml and magnesium chloride 50g, stir；
(3) it is eventually adding Polyethylene Glycol-200 and is settled to 1000ml, stir to clarify.
Products obtained therefrom is carried out fill, sterilizing, convenient storage and transport.
Embodiment 4
In every 1000ml solution, containing florfenicol 50g, DMF 100ml, Polyethylene Glycol-200 is about
550ml, glycerin methylal 50ml, magnesium chloride 70g
The preparation method of the florfenicol solution of the present embodiment, comprises the following steps:
(4) taking DMF 100ml and be warming up to 70 DEG C, add florfenicol 80g, stirring is to dissolving；
(2) add glycerin methylal 200ml and magnesium chloride 70g, stir；
(3) it is eventually adding Polyethylene Glycol-200 and is settled to 1000ml, stir to clarify.
Products obtained therefrom is carried out fill, sterilizing, convenient storage and transport.
Embodiment 5
In every 1000ml solution, containing florfenicol 100g, DMF 200ml, Polyethylene Glycol-200 is about
450ml, glycerin methylal 200ml, magnesium chloride 50g
The preparation method of the florfenicol solution of the present embodiment, comprises the following steps:
(5) take DMF 200ml and be warming up to 70 DEG C, add florfenicol 100g, stirring is extremely dissolved,
(2) add glycerin methylal 200ml and magnesium chloride 50g, stir；
(3) it is eventually adding Polyethylene Glycol-200 and is settled to 1000ml, stir to clarify.
Products obtained therefrom is carried out fill, sterilizing, convenient storage and transport.
Embodiment 6 solubization is tested
Test example: distinguish the florfenicol solution agent prepared by Example 1～5, commercially available florfenicol solution (10%)
5ml, with deionized water dilute 5 times, 10 times, 50 times, 100 times, the embodiment 1 the most at ambient temperature prepared by the present invention～
5 respectively on centrifuge 4000rpm rotating speed be centrifuged 30min, observe diluent with or without macroscopic precipitate, result such as following table
1。
Table 1 florfenicol solution of the present invention dissolubility test
Drawn by upper table: florfenicol solution of the present invention 5 times, 10 times, 50 times, under 100 times of molten water conditions, solution is still
Clear, without separating out precipitation and muddiness.Solubization is substantially better than commercially available florfenicol solution.
Embodiment 7 clinical effectiveness is tested
Lu Tai farm, Tangshan chicken house carries out clinical trial, AA broiler, 1 age in days, raises 14 days before test；
2 week old health broiler 350, are randomly divided into 7 groups, often group 50.Specifically it is grouped as follows:
Low dosage is for reagent thing group: every 1kg drinking-water adds florfenicol solution agent (embodiment of the present invention 2) (50mg/L-with
Florfenicol meter)
Middle dosage is for reagent thing group: add florfenicol solution agent (embodiment of the present invention 2) (150mg/ in every 1kg drinking-water
L-is in terms of florfenicol)
High dose is for reagent thing group: add florfenicol solution agent (embodiment of the present invention 2) (250mg/ in every 1kg drinking-water
L-is in terms of florfenicol)
Control drug group: add florfenicol powder (10%) (250mg/kg-is in terms of florfenicol) in every 1kg feedstuff
Positive infection matched group: artificial challenge escherichia coli are not administered；
Normal healthy controls group: not ehec infection, is not administered, and organizes isolated rearing with other；
Safe dose group: with 5 times of administrations of recommended dose, observe the safety of florfenicol solution agent.The most every 1kg drinks water
Middle addition florfenicol solution agent (500g/L) organizes chicken isolated rearing with other.
High, normal, basic dosage is cultivated for reagent thing group, control drug group and positive infection matched group chicken lumbar injection escherichia coli
Liquid, the respectively sensitive Escherichia coli of inoculation.After counteracting toxic substances when chicken starts to occur disease symptom, give the most respectively for reagent
Thing and control drug, continuous use 5 days.Continuous Observation 10 days after clinical observation counteracting toxic substances, note observing and recording each group of chicken every day
Group's state, clinical change and death condition.
Criterion of cure
Prothymia, searches for food, drinks water normally, and feather light, feces is normal.Drug withdrawal is slaughtered immediately after 3 days and is cutd open inspection, after cuing open inspection
Without pericarditis, airsacculitis, liver Bao Yan, peritonitis and kidney disease.
Result of the test is shown in Table 2.
Table 2 florfenicol solution clinical effect trial
Test result indicate that, florfenicol solution under the same conditions, can efficiently control chicken colibacillosis, and it is controlled
More rate is apparently higher than using control drug group.
With the above-mentioned desirable embodiment according to the present invention for enlightenment, by above-mentioned description, relevant staff is complete
Entirely can carry out various change and amendment in the range of without departing from this invention technological thought.The technology of this invention
The content that property scope is not limited in description, it is necessary to determine its technical scope according to right.
Claims (4)
1. the florfenicol solution agent that can be used for drinking water administration, it is characterised in that described solution is by florfenicol, N, N-
Dimethylformamide, Polyethylene Glycol-200, glycerin methylal, magnesium chloride form.
A kind of florfenicol solution agent that can be used for drinking water administration, it is characterised in that described often
Containing florfenicol 5～30g in 100ml florfenicol solution agent, DMF 10～25ml, glycerin methylal 5～
20ml, magnesium chloride 5～7g, surplus is polyethylene glycol 200.
A kind of florfenicol solution agent that can be used for drinking water administration, it is characterised in that described often
The 15g Han florfenicol in 100ml florfenicol solution agent, DMF 20ml, glycerin methylal 14ml, magnesium chloride
6g, surplus is polyethylene glycol 200.
4. prepare if claim 1 is to a method for a kind of florfenicol solution agent that can be used for drinking water administration as described in power 3,
It is characterized in that, comprise the following steps:
(1) taking recipe quantity DMF and be warming up to 70 DEG C, add florfenicol, stirring is to dissolving；
(2) above-mentioned solution adds recipe quantity glycerin methylal and magnesium chloride, stir；
(3) it is eventually adding Polyethylene Glycol-200 and is settled to recipe quantity, stir to clarify.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610768292.2A CN106236705A (en) | 2016-08-30 | 2016-08-30 | A kind of florfenicol solution agent that can be used for drinking water administration and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106596791A (en) * | 2016-12-28 | 2017-04-26 | 重庆金邦动物药业有限公司 | Quality standard of synergistic Florfenicol powder dry suspension |
| CN110478314A (en) * | 2019-09-27 | 2019-11-22 | 上海明磊邦森生物科技(登封)有限公司 | Florfenicol solution and its preparation method and application that can be miscible with water with arbitrary proportion |
| CN111494312A (en) * | 2020-05-20 | 2020-08-07 | 山东省健牧生物药业有限公司 | Oral liquid for preventing and treating chicken colibacillosis and preparation method thereof |
| CN116036020A (en) * | 2022-08-31 | 2023-05-02 | 瑞普（天津）生物药业有限公司 | Florfenicol powder with high bioavailability and preparation method thereof |
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| WO2004014341A1 (en) * | 2002-08-13 | 2004-02-19 | Dae Han New Pharm Co., Ltd. | Oral injectable pharmaceutical composition comprising florfenicol as an active ingredient |
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| CN104127430A (en) * | 2014-06-30 | 2014-11-05 | 邳州正康生物技术有限公司 | Veterinary florfenicol injection, and preparation method and application thereof |
| CN104208062A (en) * | 2013-06-03 | 2014-12-17 | 中国农业科学院兰州畜牧与兽药研究所 | High-concentration compound florfenicol injection, and preparation method and application thereof |
| CN105796488A (en) * | 2016-03-23 | 2016-07-27 | 张先碧 | Florfenicol solution preparation and preparation method thereof |
| CN105878179A (en) * | 2014-12-15 | 2016-08-24 | 沈阳伟嘉牧业技术有限公司 | Preparation method and application of florfenicol solution |
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| WO2004014341A1 (en) * | 2002-08-13 | 2004-02-19 | Dae Han New Pharm Co., Ltd. | Oral injectable pharmaceutical composition comprising florfenicol as an active ingredient |
| 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 |
| CN104208062A (en) * | 2013-06-03 | 2014-12-17 | 中国农业科学院兰州畜牧与兽药研究所 | High-concentration compound florfenicol injection, and preparation method and application thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106596791A (en) * | 2016-12-28 | 2017-04-26 | 重庆金邦动物药业有限公司 | Quality standard of synergistic Florfenicol powder dry suspension |
| CN110478314A (en) * | 2019-09-27 | 2019-11-22 | 上海明磊邦森生物科技(登封)有限公司 | Florfenicol solution and its preparation method and application that can be miscible with water with arbitrary proportion |
| CN110478314B (en) * | 2019-09-27 | 2022-01-11 | 上海明磊邦森生物科技(登封)有限公司 | Florfenicol solution capable of being mutually dissolved with water in any proportion and preparation method and application thereof |
| CN111494312A (en) * | 2020-05-20 | 2020-08-07 | 山东省健牧生物药业有限公司 | Oral liquid for preventing and treating chicken colibacillosis and preparation method thereof |
| CN116036020A (en) * | 2022-08-31 | 2023-05-02 | 瑞普（天津）生物药业有限公司 | Florfenicol powder with high bioavailability and preparation method thereof |
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Application publication date: 20161221 |