CN109464391A - A kind of injection and preparation method thereof - Google Patents
A kind of injection and preparation method thereof Download PDFInfo
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- CN109464391A CN109464391A CN201910030281.8A CN201910030281A CN109464391A CN 109464391 A CN109464391 A CN 109464391A CN 201910030281 A CN201910030281 A CN 201910030281A CN 109464391 A CN109464391 A CN 109464391A
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- injection
- ceftiofur
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic 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
- A61K31/542—Heterocyclic 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
- A61K31/545—Compounds 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
- A61K31/546—Compounds 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
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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
- A61K47/12—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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- 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
Abstract
The present invention relates to a kind of injection and preparation method thereof, injection includes 2.5~10 parts of Ceftiofur zinc；0.1~5 part of suspending agent；0.1~5 part of thickener；0.1~0.5 part of antioxidant, 0.1~1 part of pH adjusting agent, 0.1~0.5 part of bacteriostatic agent, solvent polishing is to 100 parts.Injection of the present invention, property are stablized, are easily dispersed again, rapid long-acting combines, significant effect.The preparation method of injection, comprising the following steps: thickener, suspending agent, antioxidant, pH adjusting agent, bacteriostatic agent are added separately in injection water, stirred to dissolve；Then Ceftiofur zinc is added to solvent, be slowly heated, stirring to dissolution；When the solution of final step (2) preparation is added in the solution of step (1), stirring while adding, injection water constant volume sterilizes to obtain the final product.Injection of the present invention, property are stablized, are easily dispersed again, rapid long-acting combines, significant effect.
Description
Technical field
The invention belongs to animal drug field preparation technical field, it is related to a kind of injection and preparation method thereof.
Background technique
Ceftiofur (Ceftiofur) also known as Ceftlofur are the third generation cephalo antibiotics of animal specific.Cephalo thiophene
Furan has spectrum bactericidal effect, and antibacterial activity is strong, effective to gram-positive bacteria and negative bacterium (including producing lactamase bacterium).
Its sensitive bacteria mainly has pasteurella multocida, pasteurella haemolytica, Actinobacillus pleuropneumoniae, salmonella, large intestine bar
Bacterium, streptococcus, staphylococcus, haemophilus etc., are not likely to produce antibody-resistant bacterium and cross resistance, are mainly used for treating a variety of dynamic
Various infection, are widely used in animal husbandry caused by object sensitive bacteria.
Ceftiofur itself facile hydrolysis, temperature sensitive, stability is poor.When Ceftiofur oral administration, on the one hand
It since raw material smell is larger, easily disperses, keeps its palatability poor, influence feed intake；On the other hand, it because its drainage rate is fast, needs
Increase administration number of times, is unfavorable for reaching efficient therapeutic effect.Therefore.Drug administration by injection is mostly used on veterinary clinic at present.
Ceftiofur oil suspension injection is the primary formulation applied at present, and said preparation is by Ceftiofur or its hydrochloride
It is suspended in vegetable oil or other oil type liquids, represents the ceftiofur crystalline suspension injection that drug is the production of Shuo Teng company, the U.S.
Liquid.But such preparation, using vegetable oil or other oils as decentralized medium, formulation viscosity is big, poor biocompatibility, it is not only clinical
Injection is not easy, and easily causes the adverse reaction of pain and injection site.Therefore still it is badly in need of stable, low adverse reaction at present
Ceftiofur formulation while guaranteeing its clinical efficacy, increases the compliance of animal to reach therapeutic purposes.
Summary of the invention
Technical problem to be solved by the invention is to provide a kind of injections and preparation method thereof.Injection master of the invention
Material be Ceftiofur zinc or its Ceftiofur Hydrochloride zinc, it is highly stable in aqueous solution, will not occur hydrolytic dissociation reaction, and
PH is controlled in 5~7 ranges, the viscosity of injection and the irritation to muscle can be greatly reduced, cost also has significantly
It reduces.
To solve the above problems, the present invention adopts the following technical scheme:
A kind of injection, including following component, according to the mass fraction: 2.5~15 parts of Ceftiofur zinc, suspending agent 0.1~5
Part, 0.1~5 part of thickener, 0.1~0.5 part of antioxidant, 0.1~1 part of pH adjusting agent, 0.1~0.5 part of bacteriostatic agent, solvent are mended
Together to 100 parts.The preparation method of Ceftiofur zinc of the invention is
As the further improvement of above-described embodiment, the Ceftiofur zinc includes its hydrochloride.
As the further improvement of above-described embodiment, injection, 10 parts of Ceftiofur zinc；2 parts of suspending agent；Thickener 0.5
Part；0.2 part of antioxidant；PH adjusting agent, solvent polishing is to 100 parts.
As the further improvement of above-described embodiment, the suspending agent is sapn, soybean lecithin, lecithin, tween, wave Lip river
One or more of husky nurse.
As the further improvement of above-described embodiment, the thickener is sodium carboxymethylcellulose, polyvinylpyrrolidone
Or one or more of rilanit special.
As the further improvement of above-described embodiment, the antioxidant is formaldehyde condensation sodium hydrosulfide.
As the further improvement of above-described embodiment, the pH adjusting agent is sodium citrate.
As the further improvement of above-described embodiment, the pH of the injection is 5~7
As the further improvement of above-described embodiment, the bacteriostatic agent is methylparaben and propylben.
As the further improvement of above-described embodiment, the solvent be N-Methyl pyrrolidone, n,N dimethylformamide,
Dimethyl sulfoxide, N, the mixture of one or more of N dimethyl acetamide and water.
As the further improvement of above-described embodiment, 20 μm of partial size of the Ceftiofur zinc are below 95% or more,
There must not be 50 μm or more of particle.
Another object of the present invention is to provide a kind of preparation methods of injection, comprising the following steps:
(1) suspending agent, thickener, antioxidant, pH adjusting agent, bacteriostatic agent are added separately in injection water, stirring makes
It is dissolved；
(2) Ceftiofur zinc is added to organic solvent, be slowly heated, stirring to dissolution；
(3) when the solution of step (2) preparation is added in the solution of step (1), stirring while adding, injection water constant volume goes out
Bacterium to obtain the final product.(this step is to facilitate Ceftiofur zinc that (side edged analysis is slowly precipitated in the order described above in injection preparation
Out)；If reverse order plus early period will not be precipitated, can be precipitated rapidly after arrival is a certain amount of very much, and granularity is larger unqualified.
As the further improvement of above-described embodiment, it is slowly heated in step (2) whipping process, the rate of heat addition 3
DEG C/min, heating and temperature control is at 55~60 DEG C；The organic solvent is N-Methyl pyrrolidone, N, N-dimethylformamide, two
Methyl sulfoxide or N, one or more of N dimethyl acetamide.
As the further improvement of above-described embodiment, in step (3), product prepared by step (2) is added in (1)
When, stirring while adding, agitating paddle radius is not less than 10cm, and mixing speed is 90~120r/min.The purpose of this step is to give way
Rapid 2 solution rapid dispersion is into the solution of step 1, and then Ceftiofur zinc is slowly precipitated.
Ceftiofur zinc purity of the invention is needed 97% or more, and corresponding preparation method is also that present invention research is visited
What rope went out are as follows: raw material is dissolved in organic solvent, after stirring and dissolving, is slowly added to zinc acetate dihydrate, it is solid gradually to generate white
Body finishes, and temperature is maintained to continue stirring a period of time, and solid washing is after filtering to get the Zn complex；The raw material is salt
Sour Ceftiofur, Ceftiofur or ceftiofur sodium.Wherein the molar ratio of raw material and zinc acetate dihydrate is 1:1~10；Raw material exists
The concentration of organic solvent are as follows: 0.05-1mol/L.Maintain temperature at -10~10 DEG C.The time for continuing stirring is 1~8 hour.Have
Solvent is one of methanol, ethyl alcohol or THF.The number of washing be it is primary, use water volume when washing is organic with when reacting
It is 1:3 that the ratio between volume, which is added, in Solvents Solvent.
The preparation principle of Ceftiofur zinc of the invention is to adopt since the raw materials such as Ceftiofur Hydrochloride are easy degradation in water
It is easy to produce impurity with the mixed solvent reaction after addition water, finished product purity is relatively low, and can not purify, and is not suitable for doing drug
It uses, and the present invention is reacted using single solvent, improves product purity to 97% or more, meets the quality requirements of drug.
The specific reaction process of Ceftiofur zinc used in the embodiment of the present invention is, by 56.0g (0.1mol) hydrochloric acid cephalo
Thiophene furan is dissolved in 1500mL methanol, and dissolution is stirred at room temperature, and is cooled to 0 DEG C, is slowly added to 32.8g (0.15mol) zinc acetate dihydrate,
Gradually generate white solid, the molar ratio of Ceftiofur Hydrochloride and zinc acetate dihydrate is 1:1.5, is finished, and temperature is maintained to continue to stir
It mixes 3 hours, filters, 500mL washing is added once to get Ceftiofur zinc product 56.0g, yield 100%, purity in solid
98%.
Ceftiofur zinc and mixed in hydrochloric acid stirring can obtain Ceftiofur Hydrochloride zinc.
Beneficial effect
1, injection solvent of the invention is mainly water, and controls pH in 5~7 ranges, can greatly reduce injection
The viscosity of liquid and irritation to muscle, cost are also significantly reduced.
2. injection major ingredient of the invention is Ceftiofur zinc or its Ceftiofur Hydrochloride zinc, very steady in aqueous solution
It is fixed, hydrolytic dissociation reaction will not occur.
3. sodium citrate is added in injection and not only increases its stability, sodium citrate-thickener system by the present invention
So that the partial size for the main ingredient being finally precipitated at 20 μm hereinafter, do not need the operation ground again, simplify step, save consumption
Can, considerably reduce cost.
4. be metabolized as Ceftiofur and zinc ion after injection intramuscular injection of the present invention in vivo, slow-absorbing, effective blood medicine is dense
It spends up to 72h and is better than oil formulation.
Detailed description of the invention
Fig. 1 is the absorption characteristic figure of injection and Ceftiofur Hydrochloride injecta in the prior art of the invention；
Fig. 2 is the observation chart (10*40 times) of the invention under injection microscope.
Specific embodiment
The invention will be further elucidated with reference to specific embodiments.It should be understood that these embodiments are merely to illustrate this hair
It is bright rather than limit the scope of the invention.In addition, it should also be understood that, after reading the content taught by the present invention, art technology
Personnel can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited
Fixed range.
All number marks, such as pH, temperature, time, concentration, including range, are all approximations.It is to be understood that although
Term " about " is all added before always not describing all number marks explicitly.While it will also be understood that, although always not clear
Narration, reagent described herein is only example, and equivalent is known in the art.
Test reagent consumptive material used in following embodiment is unless otherwise specified conventional biochemical reagent；The experiment
Method is unless otherwise specified conventional method；Quantitative test in following embodiment is respectively provided with three repeated experiments, as a result
It is averaged.
Embodiment 1
A kind of injection is by Ceftiofur zinc；Suspending agent；Thickener；Antioxidant；PH adjusting agent；Bacteriostatic agent；Solvent
Polishing contains Ceftiofur zinc 10g, lecithin 1.2g, sodium carboxymethylcellulose to 100 parts in specially every 100mL solution
2.0g, formaldehyde condensation sodium hydrosulfide 0.2g, sodium citrate 0.4g, methylparaben 0.05g, propylben 0.05g, N- methyl
Pyrrolidones 30mL, injection water polishing to 100mL.
Injection the preparation method comprises the following steps:
(1) by lecithin, sodium carboxymethylcellulose, formaldehyde condensation sodium hydrosulfide, sodium citrate, methylparaben, Ni Bo
Golden propyl ester is separately added into injection water, is stirred to dissolve.
(2) Ceftiofur zinc is added to N-Methyl pyrrolidone, be slowly heated, the rate of heat addition is 3 DEG C/min, and stirring is extremely
Dissolution, 55 DEG C of heating temperature.
(3) when the solution of step (2) preparation is added in the solution of step (1), stirring while adding, agitating paddle radius is not small
In 10cm, mixing speed 120r/min, water for injection constant volume sterilizes to obtain the final product.Through Ceftiofur made from above-mentioned preparation method
In zinc injection, the partial size of Ceftiofur zinc is at 20 μm hereinafter, as shown in Figure 2.
Embodiment 2
A kind of injection is by Ceftiofur Hydrochloride zinc；Suspending agent；Thickener；Antioxidant；PH adjusting agent；Bacteriostatic agent；
Solvent polishing contains Ceftiofur Hydrochloride zinc 8.0g, Tween-80 2.0g, polyethylene to 100 parts in specially every 100mL solution
Pyrrolidones K30 2.5g, formaldehyde condensation sodium hydrosulfide 0.2g, sodium citrate 0.7g, methylparaben 0.03g, propylben
0.08g, dimethyl sulfoxide 25mL, injection water polishing to 100mL.
Injection the preparation method comprises the following steps:
(1) by Tween-80, PVP K30, formaldehyde condensation sodium hydrosulfide, sodium citrate, methylparaben,
Propylben is separately added into injection water, is stirred to dissolve.
(2) Ceftiofur zinc is added in dimethyl sulfoxide, is slowly heated, the rate of heat addition is 3 DEG C/min, is stirred to molten
Solution, 58 DEG C of heating temperature.
(3) when the solution of step (2) preparation is added in the solution of step (1), stirring while adding, agitating paddle radius is not small
In 10cm, mixing speed 115r/min, water for injection constant volume sterilizes to obtain the final product.Through Ceftiofur made from above-mentioned preparation method
In zinc injection, the partial size of Ceftiofur zinc is at 20 μm or less.
Embodiment 3
A kind of injection is by Ceftiofur zinc；Suspending agent；Thickener；Antioxidant；PH adjusting agent；Bacteriostatic agent；Solvent
Polishing to 100 parts, in specially every 100mL solution containing Ceftiofur zinc 5.0g, Tween-80 1.0g, soybean lecithin 0.5g,
Rilanit special 2.0g, formaldehyde condensation sodium hydrosulfide 0.2g, sodium citrate 0.3g, methylparaben 0.03g, propylben
0.08g, N, N-dimethylformamide 15mL, injection water polishing to 100mL.
Injection the preparation method comprises the following steps:
(1) by Tween-80, soybean lecithin, rilanit special, formaldehyde condensation sodium hydrosulfide, sodium citrate, Metagin
Ester, propylben are separately added into injection water, are stirred to dissolve.
(2) Ceftiofur zinc is added in n,N dimethylformamide, is slowly heated, the rate of heat addition is 3 DEG C/min, is stirred
It mixes to dissolution, heating temperature is at 60 DEG C.
(3) when the solution of step (2) preparation is added in the solution of step (1), stirring while adding, agitating paddle radius is not small
In 10cm, mixing speed is 90~120r/min, and water for injection constant volume sterilizes to obtain the final product.Through cephalo made from above-mentioned preparation method
In thiophene furan zinc injection, the partial size of Ceftiofur zinc is at 20 μm or less.
Embodiment 4
A kind of injection is by Ceftiofur zinc；Suspending agent；Thickener；Antioxidant；PH adjusting agent；Bacteriostatic agent；Solvent
Polishing contains Ceftiofur zinc 12.0g, poloxamer F188 1.0g, hydrogenated castor to 100 parts in specially every 100mL solution
Oily 2.0g, formaldehyde condensation sodium hydrosulfide 0.2g, sodium citrate 0.3g, methylparaben 0.03g, propylben 0.08g, N, N
Dimethyl acetamide 15mL, injection water polishing to 100mL.
Injection the preparation method comprises the following steps:
(1) by poloxamer F188, rilanit special, formaldehyde condensation sodium hydrosulfide, sodium citrate, methylparaben, Buddhist nun
It moors golden propyl ester to be separately added into injection water, stir to dissolve.
(2) Ceftiofur zinc is added to N, in N dimethyl acetamide, slow heating, the rate of heat addition is 3 DEG C/min, is stirred
It mixes to dissolution, heating temperature is at 57 DEG C.
(3) when the solution of step (2) preparation is added in the solution of step (1), stirring while adding, agitating paddle radius is not small
In 10cm, mixing speed is 90~120r/min, and water for injection constant volume sterilizes to obtain the final product.Through cephalo made from above-mentioned preparation method
In thiophene furan zinc injection, the partial size of Ceftiofur zinc is at 20 μm or less.
Embodiment 5
A kind of injection is by Ceftiofur zinc；Suspending agent；Thickener；Antioxidant；PH adjusting agent；Bacteriostatic agent；Solvent
Polishing contains Ceftiofur Hydrochloride zinc 12.0g, soybean lecithin 2.0g, hydrogenated castor to 100 parts in specially every 100mL solution
Oily 2.0g, formaldehyde condensation sodium hydrosulfide 0.2g, sodium citrate 0.3g, methylparaben 0.03g, propylben 0.08g, N, N
Dimethyl acetamide 15mL, injection water polishing to 100mL.
Injection the preparation method comprises the following steps:
(1) by soybean lecithin, rilanit special, formaldehyde condensation sodium hydrosulfide, sodium citrate, methylparaben, nipalgin
Propyl ester is separately added into injection water, is stirred to dissolve.
(2) Ceftiofur Hydrochloride zinc is added to N, in N dimethyl acetamide, slow heating, the rate of heat addition is 3 DEG C/
Min, stirring is to dissolving, and heating temperature is at 55 DEG C.
(3) when the solution of step (2) preparation is added in the solution of step (1), stirring while adding, agitating paddle radius is not small
In 10cm, mixing speed is 90~120r/min, and water for injection constant volume sterilizes to obtain the final product.Through cephalo made from above-mentioned preparation method
In thiophene furan zinc injection, the partial size of Ceftiofur zinc is at 20 μm or less.
Embodiment 6
A kind of injection is by Ceftiofur zinc；Suspending agent；Thickener；Antioxidant；PH adjusting agent；Bacteriostatic agent；Solvent
Polishing contains Ceftiofur zinc 15g, sapn 3.0g, soybean lecithin 2.0g, polyethylene to 100 parts in specially every 100mL solution
Pyrrolidones 5.0g, formaldehyde condensation sodium hydrosulfide 0.5g, sodium citrate 1g, methylparaben 0.15g, propylben 0.35g,
N, N dimethyl acetamide 15mL, dimethyl sulfoxide 20mL, injection water polishing to 100mL.
Injection the preparation method comprises the following steps:
(1) by soybean lecithin, sapn, polyvinylpyrrolidone, formaldehyde condensation sodium hydrosulfide, sodium citrate, Metagin
Ester, propylben are separately added into injection water, are stirred to dissolve.
(2) Ceftiofur zinc is added to N, in N dimethyl acetamide and dimethyl sulfoxide, slow heating, the rate of heat addition
For 3 DEG C/min, stirring is to dissolving, and heating temperature is at 60 DEG C.
(3) when the solution of step (2) preparation is added in the solution of step (1), stirring while adding, agitating paddle radius is not small
In 10cm, mixing speed 120r/min, water for injection constant volume sterilizes to obtain the final product.Through Ceftiofur made from above-mentioned preparation method
In zinc injection, the partial size of Ceftiofur zinc is at 20 μm or less.
Embodiment 7
A kind of injection is by Ceftiofur zinc；Suspending agent；Thickener；Antioxidant；PH adjusting agent；Bacteriostatic agent；Solvent
Polishing contains Ceftiofur Hydrochloride zinc 2.5g, lecithin 0.1g, carboxymethyl cellulose to 100 parts in specially every 100mL solution
Sodium 0.1g, formaldehyde condensation sodium hydrosulfide 0.1g, sodium citrate 0.1g, methylparaben 0.04g, propylben 0.06g, diformazan
Base sulfoxide 20mL, injection water polishing to 100mL.
Injection the preparation method comprises the following steps:
(1) by lecithin, polyvinylpyrrolidone, formaldehyde condensation sodium hydrosulfide, sodium citrate, methylparaben, Ni Bo
Golden propyl ester is separately added into injection water, is stirred to dissolve.
(2) Ceftiofur Hydrochloride zinc is added in dimethyl sulfoxide, is slowly heated, the rate of heat addition is 3 DEG C/min, stirring
To dissolution, heating temperature is at 60 DEG C.
(3) when the solution of step (2) preparation is added in the solution of step (1), stirring while adding, agitating paddle radius is not small
In 10cm, mixing speed 90r/min, water for injection constant volume sterilizes to obtain the final product.Through Ceftiofur zinc made from above-mentioned preparation method
In injection, the partial size of Ceftiofur zinc is at 20 μm or less.
Embodiment 8
A kind of injection is by Ceftiofur zinc；Suspending agent；Thickener；Antioxidant；PH adjusting agent；Bacteriostatic agent；Solvent
Polishing contains Ceftiofur Hydrochloride zinc 5g, lecithin 1g, sodium carboxymethylcellulose to 100 parts in specially every 100mL solution
0.5g, polyvinylpyrrolidone 1.6g, formaldehyde condensation sodium hydrosulfide 0.3g, sodium citrate 0.5g, methylparaben 0.1g, Ni Bo
Golden propyl ester 0.15g, dimethyl sulfoxide 30mL, injection water polishing to 100mL.
Injection the preparation method comprises the following steps:
(1) by lecithin, sodium carboxymethylcellulose, polyvinylpyrrolidone, formaldehyde condensation sodium hydrosulfide, sodium citrate,
Methylparaben, propylben are separately added into injection water, are stirred to dissolve.
(2) Ceftiofur Hydrochloride zinc is added in dimethyl sulfoxide, is slowly heated, the rate of heat addition is 3 DEG C/min, stirring
To dissolution, heating temperature is at 60 DEG C.
(3) when the solution of step (2) preparation is added in the solution of step (1), stirring while adding, agitating paddle radius is not small
In 10cm, mixing speed 90r/min, water for injection constant volume sterilizes to obtain the final product.Through Ceftiofur zinc made from above-mentioned preparation method
In injection, the partial size of Ceftiofur zinc is at 20 μm or less.
Function detection
1 stability test of test example
(1) hot test
It places 10 days, injection described in the embodiment of the present invention 1 prepared in the 5th day under the conditions of being placed in 60 DEG C
It was sampled with the 10th day, detects related index.The result shows that said preparation meets injection standard, there is no significant changes.
(2) high humidity test
By injection described in the embodiment of the present invention 1 prepared, it is placed in 25 DEG C, relative humidity (RH) (90 ± 5) %
Under the conditions of place 10 days, the 5th day and the 10th day sample detection.The result shows that moisture absorption weight gain is below 5%.
(3) strong illumination is tested
By injection described in the embodiment of the present invention 1 prepared, it is placed in lighting box and illumination equipped with fluorescent lamp
It is placed 10 days under the conditions of 4500 ± 500lx, the 5th day and the 10th day sample detection.The result shows that content, character are without obvious poor
It is different.
(4) accelerated test
By injection described in the embodiment of the present invention 3 prepared, it is placed in the condition of (40 ± 2) DEG C, RH (75 ± 5) %
Under, test within 6 months.The 0th during test, 1,2,3,6 the end of month sample detection contents, character no significant difference.
The injection local stimulation test of the present invention of test example 2
(1) material and method
(1) trial drug: the injection of embodiment 1
(2) experimental animal: rabbit
(3) test method: healthy rabbits 24, half male and half female is randomly divided into 2 groups, and every group 12, first group of injection is above-mentioned
Injection, the molten glucose injection such as second group of injection, once a day, and for three days on end, injection front and back iodine tincture disinfection, in note
The variation for shooting away 24 hours, observing injection site after a week, every group execution rabbit 6 every time, whether there is or not oedema, hyperemia, bad for observation
It waits indefinitely significant irritative response.
(2) result judgment criteria
Injection site and surrounding tissue are observed whether there is or not oedema, hyperemia, necrosis, tissue edema, hyperemia, degree of necrosis be divided into 0,
I, II, III degree, 0 degree to be unchanged, I degree is slight change, and II degree is significant change, and III degree is seriously to change.
(3) test result
Injection irritant test result see the table below
| Group | Observing time | It is congested | Oedema | Necrosis |
| Control group | 24 hours | 0 | 0 | 0 |
| Ceftiofur | 24 hours | 1 | 0 | 0 |
| Control group | 7 days | 0 | 0 | 0 |
| Ceftiofur | 7 days | 0 | 0 | 0 |
Experiments have shown that injection of the invention is substantially nonirritant, it is highly-safe.
3 pharmacokinetic trial of test example
On Tianjin pig farm, healthy growing and fattening pigs 12 are taken, are randomly divided into 2 groups, 1 group is prepared with the embodiment of the present invention 1
Injection, 2 groups are measured according to prevention dosage progress intramuscular injection in different time with the common Ceftiofur Hydrochloride injecta in market
Ceftiofur concentration (6 are averaged) in interior blood, Fig. 1 shows the absorption characteristic of different preparations, as seen from the figure,
In the case where same medicine, using injection made from production method of the present invention and the common Ceftiofur Hydrochloride injecta in market
It compares, area under the drug-time curve significantly improves, and drug uptake rate is high, slow releasing function significant effect.
Claims (10)
1. a kind of injection, it is characterised in that: including following component, according to the mass fraction: 2.5~15 parts of Ceftiofur zinc helps
0.1~5 part of suspension, 0.1~5 part of thickener, 0.1~0.5 part of antioxidant, 0.1~1 part of pH adjusting agent, bacteriostatic agent 0.1~
0.5 part, solvent polishing is to 100 parts.
2. injection according to claim 1, it is characterised in that: the Ceftiofur zinc includes its hydrochloride.
3. injection according to claim 1, it is characterised in that: including following component, according to the mass fraction: Ceftiofur
10 parts of zinc, 2 parts of suspending agent, 0.5 part of thickener, 0.2 part of antioxidant, 0.4 part of pH adjusting agent, 0.2 part of bacteriostatic agent, solvent polishing
To 100 parts.
4. injection according to claim 1, it is characterised in that: the suspending agent be sapn, soybean lecithin, lecithin,
One or more of tween or poloxamer；The thickener is sodium carboxymethylcellulose, polyvinylpyrrolidone or hydrogenation
One or more of castor oil.
5. injection according to claim 1, it is characterised in that: the antioxidant is formaldehyde condensation sodium hydrosulfide；Institute
Stating pH adjusting agent is sodium citrate；The bacteriostatic agent is methylparaben and propylben.
6. injection according to claim 1, it is characterised in that: the solvent is that the mixing that organic solvent and water form is molten
Agent；The organic solvent is N-Methyl pyrrolidone, N, N-dimethylformamide, dimethyl sulfoxide or N, in N dimethyl acetamide
One or more.
7. injection according to claim 1, it is characterised in that: in injection, the partial size of Ceftiofur zinc 20 μm with
Under.
8. the preparation method of -7 any injections according to claim 1, which comprises the following steps:
(1) thickener, suspending agent, antioxidant, pH adjusting agent, bacteriostatic agent are added separately in injection water, stirring keeps its molten
Solution；
(2) Ceftiofur zinc is added in organic solvent, is slowly heated, stirring to dissolution；
(3) solution prepared by step (2) is added in the solution of step (1) preparation, stirring while adding, injection water constant volume goes out
Bacterium to obtain the final product.
9. injection preparation according to claim 8, it is characterised in that: it is slowly heated in step (2) whipping process,
The rate of heat addition is 3 DEG C/min, and heating and temperature control is at 55~60 DEG C.
10. injection preparation according to claim 8, it is characterised in that: in step (3), by step (2) preparation
It is stirring while adding when solution is added in the solution of step (1), agitating paddle radius be not less than 10cm, mixing speed be 90~
120r/min。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910030281.8A CN109464391A (en) | 2019-01-14 | 2019-01-14 | A kind of injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910030281.8A CN109464391A (en) | 2019-01-14 | 2019-01-14 | A kind of injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109464391A true CN109464391A (en) | 2019-03-15 |
Family
ID=65678661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910030281.8A Pending CN109464391A (en) | 2019-01-14 | 2019-01-14 | A kind of injection and preparation method thereof |
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| Country | Link |
|---|---|
| CN (1) | CN109464391A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4877782A (en) * | 1988-02-16 | 1989-10-31 | The Upjohn Company | Zinc ceftiofur complexes |
| CN103191057A (en) * | 2012-01-05 | 2013-07-10 | 洛阳惠中兽药有限公司 | Aqueous suspension injection of ceftiofur, and preparation method thereof |
-
2019
- 2019-01-14 CN CN201910030281.8A patent/CN109464391A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4877782A (en) * | 1988-02-16 | 1989-10-31 | The Upjohn Company | Zinc ceftiofur complexes |
| CN103191057A (en) * | 2012-01-05 | 2013-07-10 | 洛阳惠中兽药有限公司 | Aqueous suspension injection of ceftiofur, and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 朱照静等: "《药剂学》", 31 August 2007 * |
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