CN106478669B - A kind of refining methd of high-purity hydrochloric acid Ceftiofur - Google Patents
A kind of refining methd of high-purity hydrochloric acid Ceftiofur Download PDFInfo
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- CN106478669B CN106478669B CN201610768546.0A CN201610768546A CN106478669B CN 106478669 B CN106478669 B CN 106478669B CN 201610768546 A CN201610768546 A CN 201610768546A CN 106478669 B CN106478669 B CN 106478669B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic 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; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/36—Methylene radicals, substituted by sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic 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; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/12—Separation; Purification
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Abstract
The present invention provides a kind of method for refining Ceftiofur Hydrochloride: the Ceftiofur Hydrochloride refined will be needed to be dissolved in water, in the mixed solution of organic solvent or water and organic solvent, the chlorination hydrogen molecule in solution is sloughed by alkali or ion exchange resin, the free acid crystal of Ceftiofur is precipitated from solution.Then the free acid crystal of Ceftiofur is added in organic solvent, concentrated hydrochloric acid is then added dropwise into solution, adjust pH, reaction generates Ceftiofur Hydrochloride, then it by the organic solution of Ceftiofur Hydrochloride, is slowly added dropwise into purified water, dilution crystallization generates high-purity hydrochloric acid ceftiofur crystalline.Method of the invention: simple process, strong operability, production cost is low, can stablize and prepare regular, the even particle size distribution of brilliant habit, the Ceftiofur Hydrochloride crystal product of purity > 99.7%.
Description
Technical field
The invention belongs to bulk drug for livestock chemical syntheses to purify field, and in particular to high-purity (>=99.7%) hydrochloric acid cephalo
The method of thiophene furan recrystallizing and refining purification.
Background technique
Ceftiofur Hydrochloride, (6R, 7R) -7- [2- (thiazolamine -4- base) (methoxyl group imido grpup) acetamido] -3-
[(2- furyl carbonyl) sulfidomethyl] -8- oxo -5- thia -1- azabicyclo [4.2.0] oct-2-ene -2- formic acid.English name
Claim: Ceftiofur CAS NO:103980-44-5, molecular formula: C19H17N5O7S3.HCL (see Fig. 1).Molecular weight: 560.03.Outside
It sees as off-white color to pale yellow powder.It is insoluble in water, almost insoluble in ethanol, the slightly soluble in acetone and tetrahydrofuran, In
It is readily soluble in dimethyl sulfoxide and n,N-Dimethylformamide.
Ceftiofur is semi-synthetic third generation animal specific cephalosporin.Sodium salt and hydrochloride are usually made for injection
With.Its has a broad antifungal spectrum, antibacterial activity is strong, there is powerful antibacterial activity to gram positive bacteria, gram-negative bacteria and anaerobic bacteria,
In it is close or weaker compared with first generation cephalosporin to gram-positive bacteria, it is husky to gram-negative bacteria such as Escherichia coli, typhoid fever
Door rod bacterium, killing property and pasteurella haemolytica, streptococcus etc. have powerful antibacterial activity more.It is the U.S. in 80 years 20th century
In generation, succeeds in developing.The medicine 1988 in U.S.'s Initial Public Offering, due to its excellent antibacterial activity and characteristics of pharmacokinetics, successively by
The U.S., Canada, Japan and European some national official approvals are used for controlling for the respiratory disease of beef cattle, milk cow, horse, pig, sheep
It treats.
Ceftiofur Hydrochloride has certain hygroscopicity, in addition, the remaining impurity of some of which synthesis process also can shadow
Its stability is rung, with the increase of standing time, drug itself can constantly degrade, and color burn, impurity content constantly increases,
Influence the quality of production of subsequent ceftiofur formulation product.Wherein, -2 decarburization amide cephalo of 4- ketone group Ceftiofur and 2- acetyl
The content of thiophene furan is affected to the purity and drug effect of drug.In order to reduce Ceftiofur Hydrochloride solid impurity to subsequent production
Influence, need to develop that a kind of Ceftiofur Hydrochloride content is high, stability it is high prepare purification process.The prior art only provides salt
The synthetic method of sour Ceftiofur, there is no Ceftiofur Hydrochloride that method is further purified.With Ceftiofur Hydrochloride placement and
Unreasonable storage declines Ceftiofur Hydrochloride content, and impurity increases, and can not carry out the production and use of further preparation.
For the actual demand to high-purity hydrochloric acid Ceftiofur, the present invention is using Ceftiofur Hydrochloride as raw material, by anti-
It answers, dilution crystallization prepares the free acid crystal of Ceftiofur, removes partial impurities, and then reactive crystallization obtains hydrochloric acid cephalo again
Thiophene furan further reduced the impurity content in Ceftiofur Hydrochloride, and then prepare the Ceftiofur Hydrochloride of high-purity, the hair
Bright is particular in that, whole process is divided into two-step crystallization, and crystallization process was controlled in the dilution crystallization stage, and avoids
It is uncontrollable to directly adopt crystallization process caused by reactive crystallization, is not easy to reduce so as to cause impurity content.High-purity of the invention
Ceftiofur Hydrochloride refining methd, process stabilizing are easy to control, and repeatability is strong, can stablize the production for obtaining purity > 99.7%
Product, and habit is regular, and stability is high.
102993216 A of patent CN (publication date: on March 27th, 2013) is related to a kind of side of preparation of Ceftiofur Hydrochloride
Method, mainly bulk pharmaceutical chemicals synthesis process, cephalo furan acid and 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester, after reaction, crystallization is prepared into Ceftiofur Hydrochloride.It closes
After obtaining Ceftiofur, hydrochloric acid reaction is added and obtains Ceftiofur Hydrochloride, without reference to the knot again of Ceftiofur Hydrochloride finished product
Brilliant purification process.
101654458 B of patent CN (publication date: on 2 24th, 2010) will prepare cephalo thiophene using cephalo furan acid as raw material
Furan free acid condensation reaction and ceftiofur free acid hydrochloric acid reactant salt process " treating different things alike " carry out.The patent system is for mistake
Journey, the free acid mother liquor of the Ceftiofur of preparation is directly reacted with hydrochloric acid and generates Ceftiofur Hydrochloride, and centre does not have Ceftiofur
The crystal precipitation process of free acid is slightly insufficient in terms of reducing impurity content although simplifying process.
The above patent relates generally to synthesis process: after cephalo furan acid and 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester reaction, hydrochloric acid is added and prepares salt
Sour Ceftiofur, but it is specific to the recrystallization purification of Ceftiofur Hydrochloride finished product, there are also deficiencies, in order to solve hydrochloric acid cephalo
Thiophene furan finished product, long-term placement or underproof solid product itself, the present invention specially propose the recrystallization of Ceftiofur Hydrochloride
Purifying technique.
Summary of the invention
For the deficiency and production requirement of current Ceftiofur Hydrochloride, the present invention provides it is a kind of prepare high-purity (>
99.7%) method of Ceftiofur Hydrochloride.It is different from the refining methd of above-mentioned Ceftiofur Hydrochloride.
The intermediate of present invention process route-Ceftiofur free acid is as shown in Fig. 2.
The purpose of the present invention is realized as follows: the Ceftiofur Hydrochloride refined will be needed to be dissolved in water, organic solvent
Or in the mixed solution of water and organic solvent, the chlorination hydrogen molecule in solution is sloughed by alkali, then to Ceftiofur free acid
Purified water is added in solution, the free acid crystal of Ceftiofur is precipitated from solution, after filtration drying, by Ceftiofur free acid
Crystal, which is added in organic solvent, to be dissolved, and concentrated hydrochloric acid is then added dropwise into solution, adjusts pH, and reaction generates Ceftiofur Hydrochloride, most
It afterwards by the organic solution of Ceftiofur Hydrochloride, is slowly added dropwise into purified water, dilution crystallization generates high-purity hydrochloric acid Ceftiofur
Crystal.
The preparation method of high-purity hydrochloric acid Ceftiofur of the present invention is implemented with the following technical solutions:
1, a kind of refining methd of high-purity hydrochloric acid Ceftiofur, which is characterized in that its preparation step are as follows:
A: taking Ceftiofur Hydrochloride raw material, is added in reaction kettle, and under certain temperature, the mixing of organic solvent and water is added
After stirring and dissolving, active carbon decoloring is added in liquid, and filtering obtains Ceftiofur Hydrochloride solution；
B: Ceftiofur Hydrochloride solution filtered in step A is added in reaction kettle, under certain temperature, into reaction kettle
Alkali is added dropwise and adjusts pH value, removes hydrogen chloride, purified water is added dropwise, solid is precipitated in dilution crystallization, filters, and it is dry, obtain Ceftiofur
Free acid crystal；
C, it is added organic solvent into reaction kettle 1, is added the ceftiofur free acid crystal in step B, after stirring and dissolving,
Concentrated hydrochloric acid is added into solution and adjusts pH value to 0.5-1.5.Under certain temperature, 99.7% or more purity is added into reaction kettle 2
Ceftiofur Hydrochloride crystal as crystal seed and purified water, by the water of the Ceftiofur Hydrochloride solution in reaction kettle 1 to reaction kettle 2
In, dilution crystallization, centrifugal filtration, washing, dry high-purity hydrochloric acid ceftiofur crystalline.
The organic solvent that the step A is used is dimethyl sulfoxide, and ethyl alcohol, methanol, solvent ratio-water/has in mixed solution
Solvent (v:v)=1:1-5.It is preferred that 1:2.
In the step A, temperature range is 20-45 DEG C；
The ratio of solvent and Ceftiofur Hydrochloride is (v:m) 5-20:1, preferably 5:1 in the step A；
The additional amount of active carbon is the 0.5-3% of solution total amount in the step A；
In the step B, temperature range is 20-75 DEG C, and pH value terminal is 2.5-3.3；
In the step B, the type of alkali is ammonium hydroxide, sodium hydroxide, pyridine or triethylamine；
In the step B, the rate of addition of alkali is 0.2-5ml/min；
In the step B, the dripping quantity of purified water is 1-5 times of mother liquor volume, rate of addition 1-10ml/min；
In the step C, solvent is dimethyl sulfoxide or n,N dimethylformamide；
In the step C, ratio (v:m)=2-10:1 of solvent and Ceftiofur free acid；
In the step C, temperature range is 5-45 DEG C；
In the step C, the additional amount of crystal seed is the 0.5-3% of Ceftiofur Hydrochloride quality；
In the step C, it is 0.5-1.5 that pH, which adjusts terminal,；
In the step C, the ratio of water and Ceftiofur Hydrochloride overall solution volume is (v:v)=1-10:1, preferably 5:
1。
The invention has the benefit that
Simple using method and process of the invention exquisite, strong operability, production cost is low, can stablize prepare it is brilliant practise it is regular,
Even particle size distribution, the Ceftiofur Hydrochloride crystal product of purity > 99.7%.
Detailed description of the invention
Fig. 1, Ceftiofur Hydrochloride molecular structure
Fig. 2, Ceftiofur free acid molecular structure
The free acid crystal SEM picture of Fig. 3, Ceftiofur
Fig. 4, Ceftiofur Hydrochloride crystal SEM picture
Specific embodiment
Here is the embodiment of the present invention, can the detailed explanation present invention, but the invention is not limited to following realities
Apply example.
Embodiment 1
1. weighing 100g Ceftiofur Hydrochloride raw material, it is added in reaction kettle, purified water 250ml, ethyl alcohol is then added
After stirring and dissolving, 0.5g Powdered Activated Carbon is added, after twenty minutes, it is molten to obtain Ceftiofur Hydrochloride for filtering for stirring decoloration in 250ml
Liquid；Filtered Ceftiofur Hydrochloride solution is added in reaction kettle, adjusts temperature to 20 DEG C.Into reaction kettle with 5ml/min
Speed 2.5% ammonium hydroxide is added dropwise, adjust pH value to 2.8,2500ml purified water, dilution crystallization, analysis be then added into reaction kettle
Solid out filters, dry, obtains ceftiofur free acid crystal 84.5g.
2. 170ml dimethyl sulfoxide is added in reaction kettle 1, the dry free acid crystal 84.5g of Ceftiofur is added anti-
It answers in kettle, stirring and dissolving.Then concentrated hydrochloric acid is added dropwise into reaction kettle 1, adjusts pH value to 0.5, is stirred to react 30min.To reaction
1700mL purified water and 0.43g Ceftiofur Hydrochloride (purity 99.7%) crystal seed are added in kettle 2, adjusts the temperature to 35 DEG C, it will be anti-
The Ceftiofur Hydrochloride solution in kettle 1 is answered to be added dropwise in reaction kettle 2 in aqueous solution, dilution crystallization precipitates crystal, centrifugal filtration,
Dry high-purity hydrochloric acid ceftiofur crystalline 89.6g.It is detected through HPLC, the Ceftiofur in Ceftiofur Hydrochloride product is
99.71%, 4- ketone group Ceftiofur are that 0.08%, MW537de unknown material is -2 decarburization amide Ceftiofur of 0.05%, 2- acetyl
0.16%.
Embodiment 2
1. weighing 100g Ceftiofur Hydrochloride raw material, it is added in reaction kettle, purified water 340ml, methanol is then added
After stirring and dissolving, 1.5g Powdered Activated Carbon is added in 660ml, stirring decoloration after twenty minutes, by Ceftiofur Hydrochloride solution, filtering,
Obtain Ceftiofur Hydrochloride solution.Filtered Ceftiofur Hydrochloride solution is added in reaction kettle, adjusts temperature to 50 DEG C.
2.5% sodium hydroxide solution is added dropwise with the speed of 3ml/min into reaction kettle, pH value is adjusted to 2.5, then adds into reaction kettle
Entering 3000ml purified water, solid is precipitated in dilution crystallization, filters, and it is dry, obtain ceftiofur free acid crystal 82.2g.
2. 250mlN is added in reaction kettle 1, N-dimethylformamide, temperature adjustment is to 20 DEG C, by dry Ceftiofur free acid
Crystal 82.2g is added in reaction kettle 1, stirring and dissolving.Then concentrated hydrochloric acid is added dropwise into reaction kettle 1, adjusts pH value to 1, stirring is anti-
Answer 30min.1250mL purified water and 1.5g Ceftiofur Hydrochloride crystal seed are added in reaction kettle 2, adjusts the temperature to 35 DEG C, will react
Ceftiofur Hydrochloride solution in kettle 1 is added dropwise in reaction kettle 2 in aqueous solution, and dilution crystallization precipitates crystal, centrifugal filtration, is done
It is dry to obtain high-purity hydrochloric acid ceftiofur crystalline 87.6g.It is detected through HPLC, the Ceftiofur in Ceftiofur Hydrochloride product is
99.79%, 4- ketone group Ceftiofur are that 0.05%, MW537 unknown material is -2 decarburization amide Ceftiofur of 0.06%, 2- acetyl
0.10%.
Embodiment 3
1. weighing 100g Ceftiofur Hydrochloride raw material, it is added in reaction kettle, purified water 330ml, ethyl alcohol is then added
After stirring and dissolving, 3.0g Powdered Activated Carbon is added in 1670ml, stirring decoloration after twenty minutes, by Ceftiofur Hydrochloride solution, mistake
Filter obtains Ceftiofur Hydrochloride solution.Filtered Ceftiofur Hydrochloride solution is added in reaction kettle, adjustment temperature to 45
℃.Pyridine is added dropwise with the speed of 3ml/min into reaction kettle, pH value is adjusted to 3.3, it is pure that 6000ml is then added into reaction kettle
Change water, solid is precipitated in dilution crystallization, filters, and it is dry, obtain ceftiofur free acid crystal 81.9g.
2. 450ml dimethyl sulfoxide is added in reaction kettle 1,35 DEG C of temperature adjustment, by the dry free acid crystal of Ceftiofur
81.9g is added in reaction kettle 1, stirring and dissolving.Then concentrated hydrochloric acid is added dropwise into reaction kettle 1, adjusts pH value to 1.5, is stirred to react
30min.500mL purified water and 3g Ceftiofur Hydrochloride crystal seed are added in reaction kettle 2, adjusts the temperature to 35 DEG C, it will be in reaction kettle 1
Ceftiofur Hydrochloride solution be added dropwise in reaction kettle 2 in aqueous solution, dilution crystallization precipitates crystal, centrifugal filtration, highly dry
Purity Ceftiofur Hydrochloride crystal 83.2g.It is detected through HPLC, the Ceftiofur in Ceftiofur Hydrochloride product is 99.82%, 4-
Ketone group Ceftiofur is that 0.03%, MW537 unknown material is -2 decarburization amide Ceftiofur 0.08% of 0.07%, 2- acetyl, impurity
Total amount is 0.18%.
Embodiment 4
1. weighing 100g Ceftiofur Hydrochloride raw material, it is added in reaction kettle, purified water 100ml is then added, dimethyl is sub-
Sulfone 400ml after stirring and dissolving, adds 1.0g Powdered Activated Carbon, stirring decoloration after twenty minutes, by Ceftiofur Hydrochloride solution, filtering,
Obtain Ceftiofur Hydrochloride solution.Filtered Ceftiofur Hydrochloride solution is added in reaction kettle, adjusts temperature to 50 DEG C.
2.5% ammonium hydroxide is added dropwise with the speed of 1.5ml/min into reaction kettle, pH value is adjusted to 2.8, is then added into reaction kettle
Solid is precipitated in 1000ml purified water, dilution crystallization, filters, dry, obtains ceftiofur free acid crystal 85.8g.
2. 200ml dimethyl sulfoxide is added in reaction kettle 1, temperature adjustment is to 5 DEG C, by the dry free acid crystal of Ceftiofur
85.8g is added in reaction kettle 1, stirring and dissolving.Then concentrated hydrochloric acid is added dropwise into reaction solution, adjusts pH value to 0.5, is stirred to react
30min.1000mL purified water and 0.5g Ceftiofur Hydrochloride crystal seed are added in another reaction kettle, adjusts the temperature to 35 DEG C, it will be anti-
The Ceftiofur Hydrochloride solution in kettle 1 is answered to be added dropwise in reaction kettle 2 in aqueous solution, dilution crystallization precipitates crystal, centrifugal filtration,
Dry high-purity hydrochloric acid ceftiofur crystalline 92.5g.It is detected through HPLC, the Ceftiofur in Ceftiofur Hydrochloride product is
99.72%, 4- ketone group Ceftiofur are that 0.10%, MW537d unknown material is -2 decarburization amide Ceftiofur of 0.02%, 2- acetyl
0.16%, total impurities 0.28%.
Embodiment 5
1. weighing 100g Ceftiofur Hydrochloride raw material, it is added in reaction kettle, purified water 200ml, ethyl alcohol is then added
After stirring and dissolving, 2.0g Powdered Activated Carbon is added in 400ml, stirring decoloration after twenty minutes, by Ceftiofur Hydrochloride solution, filtering,
Obtain Ceftiofur Hydrochloride solution.Filtered Ceftiofur Hydrochloride solution is added in reaction kettle, adjusts temperature to 75 DEG C.
2.5% ammonium hydroxide is added dropwise with the speed of 2ml/min into reaction kettle, pH value is adjusted to 2.7,2000ml is then added into reaction kettle
Solid is precipitated in purified water, dilution crystallization, filters, dry, obtains ceftiofur free acid crystal 87.1g.
2. 200ml dimethyl sulfoxide is added in reaction kettle 1, temperature adjustment is to 5 DEG C, by the dry free acid crystal of Ceftiofur
87.1g is added in reaction kettle 1, stirring and dissolving.Then concentrated hydrochloric acid is added dropwise into reaction solution, adjusts pH value to 1.0, is stirred to react
30min.2000mL purified water and 2.5g Ceftiofur Hydrochloride crystal seed are added in reaction kettle 2,45 DEG C are adjusted the temperature to, by reaction kettle
Ceftiofur Hydrochloride solution in 1 is added dropwise in reaction kettle 2 in aqueous solution, and dilution crystallization precipitates crystal, centrifugal filtration, dry
Obtain high-purity hydrochloric acid ceftiofur crystalline 93.2g.It is detected through HPLC, the Ceftiofur in Ceftiofur Hydrochloride product is
99.75%, 4- ketone group Ceftiofur are that 0.09%, MW537 unknown material is -2 decarburization amide Ceftiofur of 0.05%, 2- acetyl
0.11%, total impurities 0.25%.
Claims (3)
1. a kind of refining methd of high-purity hydrochloric acid Ceftiofur, which is characterized in that its preparation step are as follows:
A: taking Ceftiofur Hydrochloride raw material, is added in reaction kettle, the mixed liquor of addition organic solvent and water, after stirring and dissolving, adds
Enter active carbon decoloring, filter, obtains Ceftiofur Hydrochloride solution；
B: Ceftiofur Hydrochloride solution filtered in step A is added in reaction kettle, and alkali is added dropwise into reaction kettle and adjusts pH value
For 2.5-3.3, purified water is then added dropwise, solid is precipitated in dilution crystallization, filters, and it is dry, obtain the free acid crystal of Ceftiofur；
C: being added organic solvent into reaction kettle 1, is added the free acid crystal of Ceftiofur in step B, after stirring and dissolving, Xiang Rong
Concentrated hydrochloric acid is added in liquid and adjusts pH value to 0.5-1.5, the hydrochloric acid cephalo of purified water and purity >=99.7% is added into reaction kettle 2
Reaction kettle 2, dilution crystallization is added in Ceftiofur Hydrochloride solution in reaction kettle 1 by thiophene furan crystal seed, and centrifugal filtration is washed, dry
Obtain high-purity hydrochloric acid ceftiofur crystalline；
It is detected through HPLC, Ceftiofur > 99.7% in the product of Ceftiofur Hydrochloride crystal；
Organic solvent described in step A is one of dimethyl sulfoxide, ethyl alcohol, methanol or combination；In the mixed liquor water with
The volume ratio of organic solvent is 1:1-5；The volume mass of the mixed liquor and Ceftiofur Hydrochloride ratio is 5-20:1；The activity
The additional amount of charcoal is the 0.5-3% of solution total amount；
Active carbon bleaching temperature is 20-45 DEG C in step A；
It is 20-75 DEG C that reaction kettle described in step B, which keeps temperature range,；The alkali is ammonium hydroxide, sodium hydroxide, pyridine or three second
Amine；The rate of addition of the alkali is 0.2-5ml/min；The dripping quantity of the purified water is 1-5 times of mother liquor volume, rate of addition
For 1-10ml/min；
Organic solvent described in step C is dimethyl sulfoxide or N, one of N-dimethylformamide；The solvent and cephalo
The volume mass ratio of ceftiofur free acid crystal is 2-10:1；It is described that organic solvent is added into reaction kettle 1, it is added in step B
The free acid crystal of Ceftiofur, after stirring and dissolving, adjustment solution temperature ranges are 5-45 DEG C；The Ceftiofur Hydrochloride crystal seed
Additional amount is the 0.5-3% of Ceftiofur Hydrochloride quality；The water and Ceftiofur Hydrochloride liquor capacity ratio are 1-10:1.
2. a kind of refining methd of high-purity hydrochloric acid Ceftiofur as described in claim 1, it is characterized in that being mixed described in step A
Closing the volume ratio of water and organic solvent in liquid is 1:2；Mixed liquor and Ceftiofur Hydrochloride volume mass ratio are 5:1.
3. a kind of refining methd of high-purity hydrochloric acid Ceftiofur as described in claim 1, it is characterized in that water described in step C
It is 5:1 with Ceftiofur Hydrochloride liquor capacity ratio.
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| CN102093391A (en) * | 2009-12-09 | 2011-06-15 | 上海华理生物医药有限公司 | New preparation method of ceftiofur sodium |
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