CN109394688A - A kind of enrofloxacin injection and preparation method thereof - Google Patents
A kind of enrofloxacin injection and preparation method thereof Download PDFInfo
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- CN109394688A CN109394688A CN201811296759.3A CN201811296759A CN109394688A CN 109394688 A CN109394688 A CN 109394688A CN 201811296759 A CN201811296759 A CN 201811296759A CN 109394688 A CN109394688 A CN 109394688A
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- enrofloxacin
- injection
- cosolvent
- self
- antioxidant
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- 229960000740 enrofloxacin Drugs 0.000 title claims abstract description 143
- 238000002347 injection Methods 0.000 title claims abstract description 98
- 239000007924 injection Substances 0.000 title claims abstract description 98
- 238000002360 preparation method Methods 0.000 title abstract description 22
- 239000002904 solvent Substances 0.000 claims abstract description 19
- 239000006184 cosolvent Substances 0.000 claims abstract description 18
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 17
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 17
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- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 20
- 239000008215 water for injection Substances 0.000 claims description 20
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- 238000011049 filling Methods 0.000 claims description 6
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- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims description 5
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 claims description 5
- 229950004959 sorbitan oleate Drugs 0.000 claims description 5
- 229950011392 sorbitan stearate Drugs 0.000 claims description 5
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims description 4
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 4
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 claims description 4
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- 229940113124 polysorbate 60 Drugs 0.000 claims description 4
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- 229940068968 polysorbate 80 Drugs 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 229940087068 glyceryl caprylate Drugs 0.000 claims 1
- FATBGEAMYMYZAF-UHFFFAOYSA-N oleicacidamide-heptaglycolether Natural products CCCCCCCCC=CCCCCCCCC(N)=O FATBGEAMYMYZAF-UHFFFAOYSA-N 0.000 claims 1
- GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 claims 1
- 229960005486 vaccine Drugs 0.000 abstract description 15
- 239000002609 medium Substances 0.000 abstract description 9
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- 241000287828 Gallus gallus Species 0.000 description 17
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- 125000002811 oleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
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- 206010012735 Diarrhoea Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 206010028470 Mycoplasma infections Diseases 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
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- 241000288049 Perdix perdix Species 0.000 description 1
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- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- FIHJKUPKCHIPAT-AHIGJZGOSA-N artesunate Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@@H](OC(=O)CCC(O)=O)[C@@H]4C FIHJKUPKCHIPAT-AHIGJZGOSA-N 0.000 description 1
- 229960004991 artesunate Drugs 0.000 description 1
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- 230000009286 beneficial effect Effects 0.000 description 1
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- 230000006806 disease prevention Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 244000144992 flock Species 0.000 description 1
- 229960000469 flunixin meglumine Drugs 0.000 description 1
- MGCCHNLNRBULBU-WZTVWXICSA-N flunixin meglumine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.C1=CC=C(C(F)(F)F)C(C)=C1NC1=NC=CC=C1C(O)=O MGCCHNLNRBULBU-WZTVWXICSA-N 0.000 description 1
- 229940124307 fluoroquinolone Drugs 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 208000004396 mastitis Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000011076 safety test Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 1
- 229960001082 trimethoprim Drugs 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
Classifications
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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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- 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 or sparfloxacin
-
- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
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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
- A61K9/0019—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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dispersion Chemistry (AREA)
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Abstract
The invention discloses a kind of enrofloxacin injections, are prepared from the following components: Enrofloxacin, cosolvent, self-emulsifier, antioxidant and solvent；Wherein, the mass volume ratio of Enrofloxacin and cosolvent is 300:(60-105) g/ml；The mass ratio of Enrofloxacin and self-emulsifier is 300:(22.5-37.5)；The mass ratio of Enrofloxacin and antioxidant is 300:(2.4-4.5)；The mass volume ratio of Enrofloxacin and solvent is 300:(670-1170) g/ml.The invention also discloses the preparation methods of enrofloxacin injection.Enrofloxacin injection of the invention can be uniformly mixed with aqueous medium and be uniformly mixed with oil medium, which solves the problems, such as Enrofloxacin slightly solubility, make the content of Enrofloxacin up to 20% or more；The enrofloxacin injection is weakly acidic, and the absorption that stimulation can be reduced on the basis of ensureing that product is stablized, promotes drug enhances drug effect；The enrofloxacin injection can be used in mixed way with vaccine, solve clinical urgent need.
Description
Technical Field
The invention relates to a veterinary drug, in particular to enrofloxacin injection and a preparation method thereof.
Background
Enrofloxacin is a special fluoroquinolone medicine for animals, has the advantages of broad spectrum, high efficiency, high bioavailability, small toxic and side effects and the like, and is concerned by clinical veterinarians at home and abroad. The enrofloxacin has good effects on escherichia coli, salmonella, brucella, pasteurella, actinobacillus pleuropneumoniae, staphylococcus aureus, mycoplasma, chlamydia and the like. The enrofloxacin can be quickly and completely absorbed by intramuscular injection, has high bioavailability, is widely distributed in animal bodies, and can well enter tissues and body fluid. The enrofloxacin is mainly used for preventing and treating bacterial diseases and mycoplasma infection of livestock and poultry clinically, and has very wide application.
In the pig industry, enrofloxacin is mainly used for treating hysteritis after delivery of sows, mastitis-hysteritis-agalactia syndrome, and various digestive system and respiratory system diseases of piglets. Because most pigs are subjected to targeted individual injection administration when preventing and treating diseases, an efficient water-soluble enrofloxacin injection is the first choice. In the chicken raising industry, because the raising period is short and the diseases are complicated and changeable, the diseases are generally prevented and controlled by regularly inoculating vaccines according to a certain epidemic prevention program. In the stage of easy disease occurrence, breeders mostly select to use the enrofloxacin injection for preventing and treating drug delivery, but multiple injections not only increase the labor cost, but also easily cause stress to chicken flocks, so that the research of the enrofloxacin injection capable of being mixed with the vaccine is a good solution way. Most of chicken vaccines are made of oily media, and part of the chicken vaccines are made of aqueous media, so that research on enrofloxacin injection which can be mixed with the aqueous media and the oily media can more comprehensively meet the clinical requirements of livestock breeding.
The invention patent with the publication number of CN101361709B discloses a long-acting enrofloxacin injection and a preparation method thereof, the enrofloxacin injection is an aqueous injection which can not be mixed with an oily medium, wherein the enrofloxacin content is lower and is 5-13%, and the injection is an injection which uses sodium hydroxide and ethanolamine to adjust the pH value to be alkaline.
The invention patent of the publication No. CN101810569B discloses an enrofloxacin injection and a preparation method thereof, the enrofloxacin injection is an aqueous solution, can not be mixed with an oily medium for use, and has a neutral ph value, the solubility of enrofloxacin is reduced under the neutral condition, the product process is complicated, and the ph value needs to be repeatedly adjusted.
The invention patent of the publication No. CN102415991B discloses an enrofloxacin long-acting injection and a preparation method thereof, wherein the enrofloxacin long-acting injection is an aqueous solution added with a polymer slow-release material, can only be mixed with an aqueous medium, and cannot be uniformly mixed with an oily medium.
The invention patent of the publication number CN102697784B discloses a veterinary enrofloxacin injection and a preparation method thereof, the injection is a compound preparation consisting of enrofloxacin, artesunate, trimethoprim and flunixin meglumine, and the solvents used by the injection are propylene glycol, ethanol and water for injection, and the solvents can only be uniformly mixed with an aqueous medium and are difficult to be mixed with an oily medium, so that the aim of being used together with the oily vaccine can not be achieved.
The invention patent of the publication number CN105193709B discloses an enrofloxacin injection and a preparation method thereof, wherein the enrofloxacin injection is also a compound preparation of enrofloxacin and meglumine, is an alkaline aqueous solution, and cannot be uniformly mixed with an oily medium.
The invention patent of the publication No. CN105267142B discloses an enrofloxacin injection and a preparation method thereof, wherein the enrofloxacin injection is a low-concentration aqueous solution, the content of the enrofloxacin injection is low, the injection dosage for large animals such as pigs is large, and the irritation is large. In addition, the injection is also an aqueous solution, and cannot be used in combination with an oily vaccine for poultry.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide the high-concentration weakly acidic enrofloxacin injection which can be uniformly mixed with an aqueous medium and an oily medium. The enrofloxacin injection solves the problem of indissolvability of enrofloxacin, and ensures that the content of enrofloxacin reaches more than 20 percent; the enrofloxacin injection is faintly acid, can reduce stimulation, promote the absorption of the medicine and enhance the medicine effect on the basis of ensuring the stability of the product; the enrofloxacin injection can be mixed with vaccine for use, thus solving the urgent clinical needs.
The second purpose of the invention is to provide a preparation method of enrofloxacin injection, which is simple and has strong operability and easy realization of production and transformation; the enrofloxacin injection prepared by the preparation method has the content of more than 20 percent, is faintly acid, has the pH value of 4.5-6, has stable quality, and can be uniformly mixed with an oily medium and an aqueous medium.
One of the purposes of the invention is realized by adopting the following technical scheme:
the enrofloxacin injection is characterized by being prepared from the following components: enrofloxacin, cosolvent, self-emulsifying agent, antioxidant and solvent; wherein the mass volume ratio of the enrofloxacin to the cosolvent is 300 (60-105) g/ml; the mass ratio of the enrofloxacin to the self-emulsifying agent is 300 (22.5-37.5); the mass ratio of the enrofloxacin to the antioxidant is 300 (2.4-4.5); the mass volume ratio of the enrofloxacin to the solvent is 300 (670) -1170 g/ml.
Further, the mass volume ratio of the enrofloxacin to the cosolvent is 300 (60-105) g/ml; the mass ratio of the enrofloxacin to the self-emulsifying agent is 300: 30; the mass ratio of the enrofloxacin to the antioxidant is 300 (3-4.5); the mass volume ratio of the enrofloxacin to the solvent is 300 (670) -1125 g/ml.
Further, the cosolvent is one or more of acetic acid, hydrochloric acid, lactic acid and citric acid.
Further, the self-emulsifying agent is one or more than two of polysorbate 60, polysorbate 80, sorbitan stearate, sorbitan oleate, polyoxyethylene caprylic/capric glyceride and oleoyl polyoxyethylene glyceride.
Further, the antioxidant is sodium thiosulfate or sodium bisulfite.
Further, the solvent is one or more of propylene glycol, glycerol, ethanol, polyethylene glycol 400 and water for injection.
Further, the enrofloxacin injection is prepared from the following components: 300g of enrofloxacin, 60ml of lactic acid, 30g of caprylic/capric polyethylene glycol glyceride, 3g of sodium thiosulfate, 100ml of propylene glycol and 570ml of water for injection.
The second purpose of the invention is realized by adopting the following technical scheme:
the preparation method of the enrofloxacin injection is characterized by comprising the following steps: adding the antioxidant with the formula amount into the solvent with the formula amount, stirring for dissolving, then adding the enrofloxacin raw material with the formula amount, uniformly mixing, adding the cosolvent with the formula amount, continuously stirring to obtain a clear solution, then adding the self-emulsifying agent with the formula amount, and uniformly stirring; and finally, sequentially filtering, filling nitrogen, subpackaging and sterilizing to obtain the enrofloxacin injection.
Further, in the step of filling nitrogen and subpackaging, the residual oxygen content is controlled to be less than 2% of the volume of the enrofloxacin injection.
Further, in the sterilization step, the sterilization temperature is 100-110 ℃, and the sterilization time is 30-35 minutes.
The invention has the beneficial effects that:
1. according to the enrofloxacin injection provided by the invention, water is selected as a solute in the formula, and meanwhile, the cosolvent is added, so that under the condition of greatly increasing the solubility of enrofloxacin, the specific self-emulsifying agent is added, so that the injection forms a stable self-emulsifying system, and the self-emulsifying system can be uniformly mixed with an oily matrix and can also be uniformly mixed with an aqueous medium. The enrofloxacin injection solves the problem of indissolvability of enrofloxacin, and ensures that the content of enrofloxacin reaches more than 20 percent; the enrofloxacin injection is faintly acid, can reduce stimulation, promote the absorption of the medicine and enhance the medicine effect on the basis of ensuring the stability of the product; the enrofloxacin injection can be mixed with vaccine for use, thus solving the urgent clinical needs.
2. The enrofloxacin injection has high concentration, can reduce the injection dosage of large and medium animals such as pigs and the like, reduces stimulation and is convenient to operate; the enrofloxacin injection can be mixed with oily vaccines for poultry for use, so that the injection frequency of poultry such as chicken and the like in disease prevention and control is reduced, and the cost is saved; can be diluted with water in any proportion, and fully considers and meets the requirements of market users. The injection provided by the invention is a weakly acidic solution, and the injection has less irritation to animal organisms, and can promote the absorption of medicines and improve the drug effect. The injection provided by the invention has an obvious effect of preventing and treating pullorum disease, can greatly reduce morbidity and mortality caused by pullorum disease, and reduces economic loss.
Detailed Description
The present invention is further described below with reference to specific embodiments, and it should be noted that, without conflict, any combination between the embodiments or technical features described below may form a new embodiment.
The enrofloxacin injection is prepared from the following components: enrofloxacin, cosolvent, self-emulsifying agent, antioxidant and solvent; wherein,
the mass volume ratio of the enrofloxacin to the cosolvent is 300 (60-105) g/ml;
the mass ratio of the enrofloxacin to the self-emulsifying agent is 300 (22.5-37.5);
the mass ratio of the enrofloxacin to the antioxidant is 300 (2.4-4.5);
the mass volume ratio of the enrofloxacin to the solvent is 300 (670) -1170 g/ml.
As a further embodiment, the mass volume ratio of the enrofloxacin to the cosolvent is 300 (60-105) g/ml; the mass ratio of the enrofloxacin to the self-emulsifying agent is 300: 30; the mass ratio of the enrofloxacin to the antioxidant is 300 (3-4.5); the mass volume ratio of the enrofloxacin to the solvent is 300 (670) -1125 g/ml.
In a further embodiment, the cosolvent is one or more of acetic acid, hydrochloric acid, lactic acid, and citric acid.
In a further embodiment, the self-emulsifying agent is one or more of polysorbate 60, polysorbate 80, sorbitan stearate, sorbitan oleate, polyethylene glycol caprylate/caprate glyceride, and oleoyl polyoxyethylene glyceride.
As a further embodiment, the antioxidant is sodium thiosulfate or sodium bisulfite.
In a further embodiment, the solvent is one or more of propylene glycol, glycerol, ethanol, polyethylene glycol 400, and water for injection.
As a further embodiment, the enrofloxacin injection is prepared from the following components: 300g of enrofloxacin, 60ml of lactic acid, 30g of caprylic/capric polyethylene glycol glyceride, 3g of sodium thiosulfate, 100ml of propylene glycol and 570ml of water for injection.
A preparation method of enrofloxacin injection comprises the following steps: adding the antioxidant with the formula amount into the solvent with the formula amount, stirring for dissolving, then adding the enrofloxacin raw material with the formula amount, uniformly mixing, adding the cosolvent with the formula amount, continuously stirring to obtain a clear solution, then adding the self-emulsifying agent with the formula amount, and uniformly stirring; and finally, sequentially filtering, filling nitrogen, subpackaging and sterilizing to obtain the enrofloxacin injection.
In a further embodiment, in the nitrogen filling and subpackaging step, the residual oxygen content is controlled to be less than 2% of the volume of the enrofloxacin injection.
As a further embodiment, in the sterilization step, the sterilization temperature is 100-110 ℃, and the sterilization time is 30-35 minutes.
The following are specific examples of the present invention, and raw materials, equipments and the like used in the following examples can be obtained by purchasing them unless otherwise specified.
Example 1:
the enrofloxacin injection is prepared from the following components: 200g of enrofloxacin, 50ml of hydrochloric acid, 8015 g of polysorbate, 2g of sodium bisulfite, 115ml of propylene glycol, 85ml of glycerol and 580ml of water for injection.
A preparation method of enrofloxacin injection comprises the following steps:
mixing propylene glycol, glycerol and water for injection, adding sodium bisulfite, stirring for 5 min to dissolve, adding enrofloxacin as raw material, mixing, adding hydrochloric acid, stirring for 20 min to obtain clear solution, adding polysorbate 80, stirring for 20 min, filtering, introducing nitrogen gas, packaging, and sterilizing.
Example 2:
the enrofloxacin injection is prepared from the following components: 200g of enrofloxacin, 55ml of acetic acid, 6020 g of polysorbate, 200ml of propylene glycol, 2g of sodium thiosulfate and 570ml of water for injection.
A preparation method of enrofloxacin injection comprises the following steps:
mixing propylene glycol and water for injection, adding sodium thiosulfate, stirring for 5 min to dissolve, adding enrofloxacin as raw material, mixing, adding acetic acid, stirring for 30 min to obtain clear solution, adding polysorbate 60, stirring for 15 min, filtering, introducing nitrogen gas, packaging, and sterilizing.
Example 3:
the enrofloxacin injection is prepared from the following components: 250g of enrofloxacin, 65ml of lactic acid, 25g of sorbitan stearate, 2g of sodium bisulfite, 400250 ml of polyethylene glycol and 470ml of water for injection.
A preparation method of enrofloxacin injection comprises the following steps:
mixing polyethylene glycol 400 and water for injection, adding sodium bisulfite, stirring for 5 min to dissolve, adding enrofloxacin as raw material, mixing, adding lactic acid, stirring for 30 min to obtain clear solution, adding sorbitan stearate, stirring for 15 min, filtering, introducing nitrogen gas, packaging, and sterilizing.
Example 4:
the enrofloxacin injection is prepared from the following components: 200g of enrofloxacin, 70ml of citric acid, 20g of sorbitan oleate, 3g of sodium bisulfite, 150ml of propylene glycol and 600ml of water for injection.
A preparation method of enrofloxacin injection comprises the following steps:
uniformly mixing propylene glycol and water for injection, adding sodium bisulfite, stirring for 2 min to dissolve, adding enrofloxacin as a raw material, uniformly mixing, adding citric acid, continuously stirring for 25 min to obtain a clear solution, adding sorbitan oleate, stirring for 20 min, filtering, introducing nitrogen, packaging, and sterilizing to obtain the product.
Example 5:
the enrofloxacin injection is prepared from the following components: 300g of enrofloxacin, 60ml of lactic acid, 30g of caprylic/capric polyethylene glycol glyceride, 3g of sodium thiosulfate, 100ml of propylene glycol and 570ml of water for injection.
A preparation method of enrofloxacin injection comprises the following steps:
mixing propylene glycol and water for injection, adding sodium thiosulfate, stirring for 2 min to dissolve, adding enrofloxacin as raw material, mixing, adding lactic acid, stirring for 30 min to obtain clear solution, adding caprylic/capric polyethylene glycol glyceride, stirring for 20 min, filtering, introducing nitrogen gas, packaging, and sterilizing.
Example 6:
the enrofloxacin injection is prepared from the following components: 200g of enrofloxacin, 65ml of acetic acid, 25g of oleoyl polyoxyethylene glyceride, 2g of sodium bisulfite, 100ml of propylene glycol, 100ml of glycerol and 550ml of water for injection.
A preparation method of enrofloxacin injection comprises the following steps:
mixing propylene glycol, glycerol and water for injection, adding sodium bisulfite, stirring for 5 min to dissolve, adding enrofloxacin, mixing, adding acetic acid, stirring for 25 min to obtain clear solution, adding oleoyl polyoxyethylene glyceride, stirring for 30 min, filtering, introducing nitrogen gas, packaging, and sterilizing.
Test example 1 (compatibility test with oily vaccine)
The enrofloxacin injection samples prepared in the above examples 1-6 and the commercially available enrofloxacin injection products are respectively mixed with avian influenza vaccines (vaccines of oily media) produced by three different manufacturers at a ratio of 1:1, shaken, stood, and the layering conditions of the solutions are observed and recorded at different times, and the results show that the enrofloxacin injection prepared in the examples 1-6 can be uniformly mixed with the oily vaccines. The details are reported in table 1 below:
TABLE 1 Effect of mixing of different examples and commercial products with oily vaccines
Note: "+" indicates uniform mixing and no delamination, and "-" indicates no delamination due to non-uniform mixing.
Test example 2 (safety test for Chicken)
130 dwarf yellow chickens, Qingyuan partridge chickens, bamboo silkworms and local chickens which are raised to 15 days old under experimental conditions are randomly divided into 13 groups, wherein 1 group is a blank control group, 6 groups are single injection test groups of examples 1-6, and 6 groups are mixed injection test groups of examples 1-6 and avian influenza vaccines. The blank group was not treated at all; test groups were injected alone, samples of examples 1-6 with water for injection at a ratio of 1: after 20 dilution, each chicken is injected with 0.3ml of single dose; in the mixed injection test group, 0.3ml of the sample of examples 1 to 6 was injected into each chicken in a single dose after mixing with the avian influenza vaccine at a ratio of 1: 20. After injection, the chickens were fed for 20 days under normal conditions and observed whether adverse reactions occurred in each test group.
The results show that the chickens in each test group have no adverse reaction, the chickens grow normally, the mental state is good, the feed intake is not reduced, and the average weight increment condition is not obviously lower than that of a blank control group, so that the medicine prepared in each embodiment is safe and nontoxic, and can not bring any toxic reaction when being mixed with an oily vaccine for use.
Test example 3 (test for controlling pullorum disease)
350 chicks of 2 days old are bred for 1 week under experimental conditions, and then are randomly divided into 7 groups, wherein one group is a control group, and the other six groups are experimental groups. The control group is injected with avian influenza vaccine; the test group respectively injects the mixed liquid of the enrofloxacin injection prepared by each embodiment and the avian influenza vaccine; after injection, the chickens are continuously raised for 2 weeks, the white diarrhea occurrence of each group of chickens is observed, and the morbidity and mortality of the chickens are counted.
TABLE 2 prevention and treatment effects of enrofloxacin injection prepared in different examples on pullorum disease
| Group of | Number of onset (only) | Incidence (%) | Number of deaths (only) | Mortality (%) |
| Example 1 | 7 | 14％ | 3 | 6％ |
| Example 2 | 9 | 18％ | 2 | 4％ |
| Example 3 | 9 | 18％ | 2 | 4％ |
| Example 4 | 6 | 12％ | 1 | 2％ |
| Example 5 | 5 | 10％ | 0 | 0％ |
| Example 6 | 8 | 16％ | 2 | 4％ |
| Control group | 23 | 46％ | 8 | 16％ |
As can be seen from the above table 2, the enrofloxacin injection prepared in each example is mixed with the avian influenza vaccine for injection, has good effect of preventing and treating pullorum disease, can greatly reduce the morbidity and mortality of pullorum disease, and reduces economic loss.
The above embodiments are only preferred embodiments of the present invention, and the protection scope of the present invention is not limited thereby, and any insubstantial changes and substitutions made by those skilled in the art based on the present invention are within the protection scope of the present invention.
Claims (10)
1. The enrofloxacin injection is characterized by being prepared from the following components: enrofloxacin, cosolvent, self-emulsifying agent, antioxidant and solvent; wherein the mass volume ratio of the enrofloxacin to the cosolvent is 300 (60-105) g/ml; the mass ratio of the enrofloxacin to the self-emulsifying agent is 300 (22.5-37.5); the mass ratio of the enrofloxacin to the antioxidant is 300 (2.4-4.5); the mass volume ratio of the enrofloxacin to the solvent is 300 (670) -1170 g/ml.
2. The enrofloxacin injection of claim 1, wherein the mass volume ratio of the enrofloxacin to the cosolvent is 300 (60-105) g/ml; the mass ratio of the enrofloxacin to the self-emulsifying agent is 300: 30; the mass ratio of the enrofloxacin to the antioxidant is 300 (3-4.5); the mass volume ratio of the enrofloxacin to the solvent is 300 (670) -1125 g/ml.
3. The enrofloxacin injection of claim 1, wherein the cosolvent is one or more of acetic acid, hydrochloric acid, lactic acid, and citric acid.
4. The enrofloxacin injection of claim 1, wherein the self-emulsifying agent is one or more of polysorbate 60, polysorbate 80, sorbitan stearate, sorbitan oleate, polyethylene glycol glyceryl caprylate and polyethylene glycol glyceryl oleamide.
5. The enrofloxacin injection of claim 1, wherein the antioxidant is sodium thiosulfate or sodium bisulfite.
6. The enrofloxacin injection as defined in claim 1, wherein the solvent is one or more of propylene glycol, glycerin, ethanol, polyethylene glycol 400, and water for injection.
7. The enrofloxacin injection of claim 1, wherein the enrofloxacin injection is prepared from the following components: 300g of enrofloxacin, 60ml of lactic acid, 30g of caprylic/capric polyethylene glycol glyceride, 3g of sodium thiosulfate, 100ml of propylene glycol and 570ml of water for injection.
8. A method for preparing enrofloxacin injection according to any one of claims 1-7, which comprises the following steps:
adding the antioxidant with the formula amount into the solvent with the formula amount, stirring for dissolving, then adding the enrofloxacin raw material with the formula amount, uniformly mixing, adding the cosolvent with the formula amount, continuously stirring to obtain a clear solution, then adding the self-emulsifying agent with the formula amount, and uniformly stirring; and finally, sequentially filtering, filling nitrogen, subpackaging and sterilizing to obtain the enrofloxacin injection.
9. The method for preparing enrofloxacin injection as claimed in claim 8, wherein in the nitrogen filling and split charging step, the residual oxygen content is controlled to be less than 2% of the volume of the enrofloxacin injection.
10. The method for preparing enrofloxacin injection as defined in claim 8, wherein in the sterilization step, the sterilization temperature is 100-.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113797347A (en) * | 2021-10-21 | 2021-12-17 | 广东温氏大华农生物科技有限公司 | Water-oil two-phase cosolvent and preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102772359A (en) * | 2012-08-02 | 2012-11-14 | 挑战（天津）动物药业有限公司 | Enrofloxacin injection and preparation method thereof |
| CN104721196A (en) * | 2013-12-20 | 2015-06-24 | 青岛康地恩动物药业有限公司 | Preparation method and application of enrofloxacin and sulfadiazine silver-containing veterinary injection liquid |
| CN105456184A (en) * | 2015-12-11 | 2016-04-06 | 天津市中升挑战生物科技有限公司 | Tilmicosin injection as well as preparation method and application thereof |
| CN108079042A (en) * | 2018-01-23 | 2018-05-29 | 青岛绿曼生物工程有限公司 | A kind of propolis-containing parenteral solution and preparation method thereof |
-
2018
- 2018-11-01 CN CN201811296759.3A patent/CN109394688A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102772359A (en) * | 2012-08-02 | 2012-11-14 | 挑战（天津）动物药业有限公司 | Enrofloxacin injection and preparation method thereof |
| CN104721196A (en) * | 2013-12-20 | 2015-06-24 | 青岛康地恩动物药业有限公司 | Preparation method and application of enrofloxacin and sulfadiazine silver-containing veterinary injection liquid |
| CN105456184A (en) * | 2015-12-11 | 2016-04-06 | 天津市中升挑战生物科技有限公司 | Tilmicosin injection as well as preparation method and application thereof |
| CN108079042A (en) * | 2018-01-23 | 2018-05-29 | 青岛绿曼生物工程有限公司 | A kind of propolis-containing parenteral solution and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 崔耀明等: "20％恩诺沙星注射液的制备及稳定性研究", 《西北农林科技大学学报》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113797347A (en) * | 2021-10-21 | 2021-12-17 | 广东温氏大华农生物科技有限公司 | Water-oil two-phase cosolvent and preparation method and application thereof |
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