CN104352501A - Compound ceftiofur sodium injection - Google Patents

Compound ceftiofur sodium injection Download PDF

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Publication number
CN104352501A
CN104352501A CN201410627883.9A CN201410627883A CN104352501A CN 104352501 A CN104352501 A CN 104352501A CN 201410627883 A CN201410627883 A CN 201410627883A CN 104352501 A CN104352501 A CN 104352501A
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China
Prior art keywords
injection
ceftiofur sodium
parts
sodium
magnolol
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CN201410627883.9A
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Chinese (zh)
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CN104352501B (en
Inventor
李良洪
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CHONGQING TAITONG ANIMAL PHARMACEUTICAL Co Ltd
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CHONGQING TAITONG ANIMAL PHARMACEUTICAL Co Ltd
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Publication of CN104352501A publication Critical patent/CN104352501A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A61K31/546Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05Phenols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/08Solutions

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention provides a compound ceftiofur sodium injection with significant antibacterial action. The compound ceftiofur sodium injection comprises the following components in parts by weight: 1-4 parts of ceftiofur sodium, 1-2 parts of magnolol, 0.5-1 part of sodium sulfite, 0.5-1 part of glycine and 1-2 parts of Tween. The injection disclosed by the invention is high in stability and simple in preparation process, has a good inhibiting effect on swine escherichia coli, has an accurate curative effect on porcine colibacillosis, is capable of reducing the dosage of a prescribed preparation and shortening the treatment cycle, and has a wide market prospect.

Description

A kind of compound ceftiofur sodium injection
Technical field
The present invention relates to a kind of compound preparation of beta-lactam antibiotic, particularly relate to a kind of injection of ceftiofur sodium honokiol.
Background technology
Colibacillosis of pigs is the piglet one group of enteric infection disease caused by pathogenic Escherichia coli.Common are yellow scour of piglet, piglet pujos blancos and baby pig edema three kinds, there is enteritis, enterotoxemia for feature.Pig yellow scours is again early onset colibacillosis, is that the one of the newborn piglet caused by the escherichia coli of certain serotype is acute, lethal infectious diseases.Mainly piglet morbidity within life age in days of rear a few hours to 5, the most common with 1-3 age in days.Pig Hakuri is also known as Delayed onset colibacillosis.The piglet of main infection 10-30 age in days.Generation is had on a lot of pig farm of China.Bowel oedema disease is a kind of acute fatal disease that the toxin having hemolytic relative gene amount reproduction to produce causes.Mainly betide the piglet before and after wean.Suddenly, the course of disease is short in morbidity, and dead fast, mortality rate is high.
Escherichia coli endotoxin is the lipopolysaccharide contained in escherichia coli adventitia, is released when thalline disintegrate, and lipoid A composition wherein has endotoxic biological function, is a kind of virulence factor, acts on particularly evident in septicemia.Escherichia coli extracellular toxin divides two large classes, and the first kind is heat-labile toxin (LT) and heat-stable toxin (ST).LT has antigenicity, and molecular weight is large, and 60 degree were destroyed through 10 minutes, can activate the epithelial adenosine cyclase of intestinal blood capillary.Increase cyclic adenosine monophosphate (cAMP) to produce, make intestinal mucosa cells hypersecretion, diarrhoea and dehydration occur; And ST can activate the guanylcyclase of the graininess on ileal epithelium brushing hair, increase cGMP and produce, cause secretory diarrhea equally.
At present this disease is mainly contained to the immunity of vaccine, the modes such as antibiotic, chemicals, Chinese medicine carry out prevention and therapy.Wherein vaccine immunization, because of enteric microorganism antigen and antigenic determinant complexity, immunologic mechanism is difference slightly, and immune effect is imprecise.Along with antibacterials abuse clinically, cause the drug resistance of the antibacterials such as escherichia coli very general, as the curative effect of medication such as gentamycin, oxytetracycline, norfloxacin, norfloxacin conventional clinically reduces.Prevent with other, Therapeutic Method compares, Chinese herbal medicine has non-specific antimicrobial effect, and residual toxicity is lower, and animal generally not easily produces drug resistance to it.And Chinese medicine and Western medicine are carried out effective compatibility, the generation of Resistant strain can be slowed down.
Summary of the invention
The invention provides a kind of injection comprising ceftiofur sodium honokiol with synergetic antibacterial effect, there is good therapeutical effect to colibacillosis of pigs, greatly reduce the consumption of single preparations of ephedrine, good stability, not drug resistance, overcomes the deficiencies in the prior art part.
Technical scheme of the present invention is: a kind of compound ceftiofur sodium injection, it is characterized in that the parts by weight of each component in described compositions are: ceftiofur sodium 1-4 weight portion; Magnolol 1-2 weight portion; Sodium sulfite 0.5-1 weight portion; Glycine 0.5-1 weight portion; Tween 1-2 weight portion.The weight ratio of ceftiofur sodium honokiol is 1:1 or 2:1.Tween is selected from Tween 80 or polysorbas20.
Compared with the prior art, injection of injection ceftiofur sodium honokiol provided by the invention and preparation method thereof, has the following advantages:
1, the compound injection good stability of ceftiofur sodium honokiol provided by the invention.
2, antibacterial activity is high: in the present invention, ceftiofur sodium honokiol coordinates with specific ratio, can produce cooperative effect, when reducing dosage, farthest plays Antifungal activity.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is described in further detail.But this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following embodiment.
Embodiment 1
Ceftiofur sodium, glycine are added successively in 300ml water for injection; By tween, sodium sulfite is dissolved in 400ml water for injection, slowly adds magnolol to dissolving completely under stirring; Merge two parts of solution, mend and inject water to 1000ml, add active carbon and stir, filter, sterilizing, fill.
Embodiment 2
Ceftiofur sodium, glycine are added successively in 300ml water for injection; By tween, sodium sulfite is dissolved in 400ml water for injection, slowly adds magnolol to dissolving completely under stirring; Merge two parts of solution, mend and inject water to 1000ml, add active carbon and stir, filter, sterilizing, fill.
Embodiment 3
Ceftiofur sodium, glycine are added successively in 300ml water for injection; By tween, sodium sulfite is dissolved in 400ml water for injection, slowly adds magnolol to dissolving completely under stirring; Merge two parts of solution, mend and inject water to 1000ml, add active carbon and stir, filter, sterilizing, fill.
Embodiment 4
Pharmacological evaluation: different ratio ceftiofur sodium and magnolol in vitro activity
Materials and methods
1. test proportioning: following proportions by weight.
(1) ceftiofur sodium
(2) magnolol
(2) ceftiofur sodium+magnolol (1: 1)
(3) ceftiofur sodium+magnolol (2: 1)
(4) ceftiofur sodium+magnolol (4: 1)
(5) ceftiofur sodium+magnolol (8: 1)
2. test strain:
Minimum inhibitory concentration (MIC) measures
Adopt meat soup trace doubling dilution, magnolol and cefmetazole being diluted with sterilizing M-H meat soup is the medicinal liquid of a series of concentration.Getting 100 μ l respectively adds in micro-hole, adds certain density bacterial suspension afterwards, makes final every hole concentration be 1.5 × 10 5cFU/ml, antibacterial application liquid concentration is 37 DEG C of incubated overnight.Minimum antibiotic concentration without bacterial growth is minimum inhibitory concentration (MIC, mg/L).Result of the test is as following table:
As can be seen from the MIC data in upper table, the compound preparation that ceftiofur sodium honokiol is prepared according to a certain weight ratio is better than two kinds of folk prescription medicines far away to the inhibitory action of escherichia coli cvcc223, dosage reduces greatly, the compound preparation that both make can play antibacterial synergism, enhances antibacterial efficacy.
Clinical trial and observation of curative effect
Test grouping: be divided into 5 groups at random by making a definite diagnosis the natural occurrence piglet 250 suffering from HUANGBAI(sic) dysentery.I, II, III group is trial drug ceftiofur sodium+magnolol (2: 1) high, medium and low treatment group, presses 0.05ml/Kg body weight, 0.03ml/Kg body weight, 0.01ml/Kg body weight drug administration by injection respectively, every day 2 times, is used in conjunction 3.IV group is ceftiofur sodium injection matched group, 0.1ml/Kg body weight, and intramuscular injection, is used in conjunction 3 days at every day 2 times.V group is magnolol matched group, and by 0.1ml/Kg body weight, intramuscular injection, every day 2 times, is used in conjunction 3 days.Each test group isolated rearing, intensive care.
Observation of curative effect: Continuous Observation 15 days after medication, each group of pig perfect compound feed of feeding (not containing any antibacterials), duration of test is noted observing defecation number of times and feces state.
Result of the test is added up: add up each group of mortality rate, effective percentage, cure rate during off-test
Curative effect judging standard:
Recovery from illness: after treatment, the spirit of affected pig, appetite recover normal, and feces be strip or graininess, anus is dry, contraction,
Without red and swollen, without rebound phenomenon in seven days.
Effective: feces retrogradation after treatment, defecation frequency reduces, and anus redness does not disappear completely, and spiritual appetite makes moderate progress.
Invalid: after treatment, affected pig spirit, feces, appetite are not improved, even dead.
Trial drug treatment colibacillosis of piglet statistical effect table
Group Sample number Dead Invalid Effectively Recovery from illness Cure rate Effective percentage
I 50 0 0 50 48 96% 100%
II 50 0 0 50 48 96% 100%
III 50 0 0 50 47 94% 100%
IV 50 1 3 46 32 64% 92%
V 50 2 5 43 28 56% 86%
As seen from the above table, the compound injection of the high, normal, basic dosage of the present invention is with the obvious advantage relative to matched group on cure rate, even and if high dose, consumption is also lower than matched group.

Claims (4)

1. a compound ceftiofur sodium injection, is characterized in that the parts by weight of each component in described injection are: ceftiofur sodium 1-4 weight portion; Magnolol 1-2 weight portion; Sodium sulfite 0.5-1 weight portion; Glycine 0.5-1 weight portion; Tween 1-2 weight portion.
2. injection as claimed in claim 1, is characterized in that the weight ratio of described ceftiofur sodium honokiol is 1:1 or 2:1.
3. injection as claimed in claim 1 or 2, is characterized in that described tween is selected from Tween 80 or polysorbas20.
4. the purposes of the injection as described in claim arbitrary in claim 1-3 in the medicine of preparation treatment colibacillosis of pigs.
CN201410627883.9A 2014-11-10 2014-11-10 A kind of compound ceftiofur sodium injection Active CN104352501B (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107320466A (en) * 2017-08-16 2017-11-07 吉林大学 Medical application of the magnolol in the enzyme inhibitors of NDM 1 are prepared
CN107789357A (en) * 2016-08-31 2018-03-13 瑞普(天津)生物药业有限公司 A kind of animal compound Cefquinome sulfate breast injection and preparation method thereof
CN109908118A (en) * 2019-04-29 2019-06-21 西南大学 Magnolol and/or honokiol are improving the application in Gram-negative bacteria Antibiotic Sensitivity
WO2021068614A1 (en) * 2019-10-06 2021-04-15 吉林大学 Application of honokiol and magnolol in preparing mcr-1 enzyme inhibitor

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1813760A (en) * 2005-12-12 2006-08-09 浙江升华拜克生物股份有限公司 Ceftiofur-containing powder injection for beast
CN102106857A (en) * 2009-12-29 2011-06-29 齐鲁动物保健品有限公司 Compound ceftiofur sodium freeze-dried power injection used for injection
CN103536529A (en) * 2013-10-30 2014-01-29 游锡火 Ceftiofur-containing long-acting injection and preparation method

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1813760A (en) * 2005-12-12 2006-08-09 浙江升华拜克生物股份有限公司 Ceftiofur-containing powder injection for beast
CN102106857A (en) * 2009-12-29 2011-06-29 齐鲁动物保健品有限公司 Compound ceftiofur sodium freeze-dried power injection used for injection
CN103536529A (en) * 2013-10-30 2014-01-29 游锡火 Ceftiofur-containing long-acting injection and preparation method

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107789357A (en) * 2016-08-31 2018-03-13 瑞普(天津)生物药业有限公司 A kind of animal compound Cefquinome sulfate breast injection and preparation method thereof
CN107320466A (en) * 2017-08-16 2017-11-07 吉林大学 Medical application of the magnolol in the enzyme inhibitors of NDM 1 are prepared
CN109908118A (en) * 2019-04-29 2019-06-21 西南大学 Magnolol and/or honokiol are improving the application in Gram-negative bacteria Antibiotic Sensitivity
WO2021068614A1 (en) * 2019-10-06 2021-04-15 吉林大学 Application of honokiol and magnolol in preparing mcr-1 enzyme inhibitor

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