CN105713013A - Cefamandole nafate compound and cefamandole nafate for injection - Google Patents
Cefamandole nafate compound and cefamandole nafate for injection Download PDFInfo
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- CN105713013A CN105713013A CN201610238043.2A CN201610238043A CN105713013A CN 105713013 A CN105713013 A CN 105713013A CN 201610238043 A CN201610238043 A CN 201610238043A CN 105713013 A CN105713013 A CN 105713013A
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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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- 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
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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Abstract
The invention relates to a cefamandole nafate compound and cefamandole nafate for injection, and belongs to the technical field of medicines.The positions, with the diffraction angles 2theta of 4.86+/-0.2 degrees and 10.77+/-0.2 degrees in an X-ray powder diffraction pattern, of the cefamandole nafate compound have feature peaks; the cefamandole nafate compound has few impurities and high purity of 99.96%, and is small in granularity, large in specific surface area, high in mobility and high in stability; after the compound is put at temperature of 40+/-2 DEG C and relative humidity of 75+/-5% for 6 months under simulating marketing package conditions, all quality detection indexes have no obvious changes, it is shown that the prepared cefamandole nafate compound has higher quality stability, it is further shown that the treatment effect and safety of medicine preparations of the compound in clinical application are better guaranteed through the cefamandole nafate compound, and the cefamandole nafate compound is more suitable for being used as a raw material medicine.
Description
Technical field
The present invention relates to a kind of medicinal active ingredient and containing its preparation, particularly relate to a kind of Cefamandole nafate compounds and injection
Cefamandole nafate, belongs to pharmaceutical technology field.
Background technology
Cefamandole nafate chemical formula is 7-D-(2-methanoyl phenyl acetamide)-3 [(1-methyl isophthalic acid H-tetrazolium-5 base) thiopurine methyltransferase]-3
Cephem-4-carboxylic acid sodium salt, molecular formula is C19H17N6NaO6S2, and for second generation cephalosporin, the leather being applied to sensitivity is blue
Site infection and the abdomen such as respiratory tract, genito-urinary system, skin and soft tissue, bone and joint caused by negative bacterium, pharynx otorhinolaryngology
Film inflammation, septicemia etc..Biliary tract and intestinal infection there is good therapeutic effect.The existence form that exploitation solid drugs is new is applied to expand it,
It it is the focus of research and development at present.
Summary of the invention
In view of this, it is an object of the invention to find and provide a kind of Cefamandole nafate compounds；On the other hand one note is provided
Penetrate and use cefamandole nafate.
Of the present invention technical problem is that is realized by techniques below scheme.
Cefamandole nafate compounds, the angle of diffraction 2 θ of its X-ray powder diagram of described Cefamandole nafate compounds is 4.86,
10.77,11.44,14.75,15.15,15.48,17.09,18.25,19.37,21.43,21.74,22.95,24.55,24.86,
At 26.83 and 31.21 ± 0.2 °, there is characteristic peak；The differential scanning calorimeter collection of illustrative plates of described Cefamandole nafate compounds 80～
100 DEG C have endothermic peak, have fusing endothermic peak at 198～202 DEG C, and maximum heat absorption melt temperature is 198 DEG C；Described cephalo Meng
The thermogravimetric curve TGA collection of illustrative plates of polyester sodium compound shows, between room temperature to 220 DEG C, do not have weightlessness before substance decomposition.
A kind of method preparing above-mentioned Cefamandole nafate compounds, comprises the steps:
In methyl tertiary butyl ether(MTBE) and cefamandole nafate dissolving crude product is warmed to 40～50 DEG C, and the acetum with 30% adjusts pH
It is worth to 5.0～6.0, in 10 minutes, adds dimethyl sulfoxide, solution is kept 10 minutes at 40～50 DEG C, add methyl
Acrylic acid cooling crystallization, filters, and 60～70 DEG C are dried, obtain Cefamandole nafate compounds；Described cefamandole nafate crude product
The weight g/ volume ml ratio of consumption and methyl tertiary butyl ether(MTBE) consumption be 1: 5～10；The consumption of described dimethyl sulfoxide and methyl
The volume ratio of tertbutyl ether consumption is 0.02～0.04: 1；The consumption of described methacrylic acid and the body of methyl tertiary butyl ether(MTBE) consumption
Long-pending ratio is 0.4～0.6: 1；-5～-10 DEG C of crystallizes it are cooled to after methacrylic acid adding.
Cefamandole nafate for injection, specification is that 1.0g/ props up, 1.5g/ props up, 2.0g/ props up, and it is by the cephalo Meng described in claim 1
Being prepared from of polyester sodium compound.
A kind of method preparing above-mentioned cefamandole nafate for injection, it is characterised in that comprise the steps:
Aseptically, bottle washing procedure is through by cillin bottle purified water immersion → ultrasonic washing → purified water shower → ultrafiltration
After water shower → water for injection shower, automatically in tunnel oven, tunnel oven have the good casing of insulation, conveyer belt,
Add heat pipe and laminar flow cleaning system composition, bottle on the conveyor belt, preheated rear 320 DEG C of high temperature sterilizing, cooling in more than 5 minutes
To less than 40 DEG C, conveyer belt it is automatically fed into subpackage clean area, for subpackage；Plug is slightly washed through ultrasound wave circulation and purified water
→ purified water and ultrasound wave fine purifiation → water for injection fine purifiation → pure steam sterilization → evacuation heat-wind circulate drying → be cooled to 40 DEG C with
Down for subpackage button plug；Racking machine uses screw rod subpackage, and computer controls impulse ratio, quantitatively, by Cefamandole nafate compounds
Sterile raw material pours into bottle, uses analytical balance selective examination loading amount, bales catch plug；Buckle well the cillin bottle of plug, deliver to roll lid operation,
Aluminium lid is screened by Cover-rolling machine by oscillator, is buckled in subpackage one by one and gets well and be buckled with on the bottle of plug, and aluminium lid is rolled tightly by dog, delivers to
Lamp inspection desk, sends into packaging process after lamp inspection is qualified, and after packaging process labeling, through mounted box cartonning of examining goods, joint sealing is finished product.
Cefamandole nafate compounds of the present invention, impurity is few, and purity is high, up to 99.96%, and particle diameter is less,
Specific surface area is big, good fluidity, stability are high；Under simulation listing terms of packing, at temperature 40 DEG C ± 2 DEG C, relative humidity
Be place 6 months under the conditions of 75% ± 5% after, every quality detecting index, without notable change, illustrates the cephalo Meng prepared by the present invention
Polyester sodium compound has better quality stability, and illustrating further Cefamandole nafate compounds of the present invention more has
It is beneficial to the efficacy and saferry ensureing its pharmaceutical preparation in clinical practice, is more suitable for crude drug and uses.
Accompanying drawing explanation
The X-ray powder diagram collection of illustrative plates of Fig. 1 Cefamandole nafate compounds of the present invention.
The differential scanning calorimeter collection of illustrative plates of Fig. 2 Cefamandole nafate compounds of the present invention.
The thermogravimetric analysis collection of illustrative plates of Fig. 3 Cefamandole nafate compounds of the present invention.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is described in further details.
Embodiment 1 prepares Cefamandole nafate compounds of the present invention
In 2100ml methyl tertiary butyl ether(MTBE) and 300g cefamandole nafate dissolving crude product is warmed to 45 DEG C, and the acetic acid with 30% is molten
Liquid adjusts pH value to after 5.5, adds 63ml dimethyl sulfoxide, is kept 10 minutes at 45 DEG C by solution, add in 10 minutes
1050ml methacrylic acid is cooled to-8 DEG C of crystallizes, filters, and 65 DEG C are dried, obtain Cefamandole nafate compounds 293.4g, receive
Rate 97.8%, it is 99.96% that HPLC measures purity.
Data monitoring:
X-ray powder diagram collection of illustrative plates such as Fig. 1 of gained Cefamandole nafate compounds.
Differential scanning calorimeter collection of illustrative plates such as Fig. 2 of gained Cefamandole nafate compounds.
Thermogravimetric analysis collection of illustrative plates such as Fig. 3 of gained Cefamandole nafate compounds.
Embodiment 2 prepares Cefamandole nafate compounds of the present invention
In 1500ml methyl tertiary butyl ether(MTBE) and 300g cefamandole nafate dissolving crude product is warmed to 40 DEG C, and the acetic acid with 30% is molten
Liquid adjusts pH value to after 5.0, adds 30ml dimethyl sulfoxide, is kept 10 minutes at 40 DEG C by solution, add in 10 minutes
600ml methacrylic acid is cooled to-5 DEG C of crystallizes, filters, and 60 DEG C are dried, obtain Cefamandole nafate compounds 290.7g, yield
It is 99.36% that 96.9%, HPLC measure purity.
Embodiment 3 prepares Cefamandole nafate compounds of the present invention
In 3000ml methyl tertiary butyl ether(MTBE) and 300g cefamandole nafate dissolving crude product is warmed to 50 DEG C, and the acetic acid with 30% is molten
Liquid adjusts pH value to after 6.0, adds 120ml dimethyl sulfoxide, kept 10 minutes at 50 DEG C by solution, add in 10 minutes
Entering 1800ml methacrylic acid and be cooled to-10 DEG C of crystallizes, filter, 70 DEG C are dried, obtain Cefamandole nafate compounds 288.9g,
Yield 96.3%, it is 99.54% that HPLC measures purity.
Embodiment 4 prepares cefamandole nafate for injection of the present invention, specification: 0.5g
Prescription:
Preparation method:
Aseptically, bottle washing procedure is through by cillin bottle purified water immersion → ultrasonic washing → purified water shower → ultrafiltration
After water shower → water for injection shower, automatically in tunnel oven, tunnel oven have the good casing of insulation, conveyer belt,
Add heat pipe and laminar flow cleaning system composition, bottle on the conveyor belt, preheated rear 320 DEG C of high temperature sterilizing, cooling in more than 5 minutes
To less than 40 DEG C, conveyer belt it is automatically fed into subpackage clean area, for subpackage；Plug is slightly washed through ultrasound wave circulation and purified water
→ purified water and ultrasound wave fine purifiation → water for injection fine purifiation → pure steam sterilization → evacuation heat-wind circulate drying → be cooled to 40 DEG C with
Down for subpackage button plug；Racking machine uses screw rod subpackage, and computer controls impulse ratio, quantitatively, by the head of preparation in embodiment 1
Spore polyester in Meng sodium compound sterile raw material pours into bottle, uses analytical balance selective examination loading amount, bales catch plug；Buckle well the cillin bottle of plug,
Delivering to roll lid operation, aluminium lid is screened by Cover-rolling machine by oscillator, is buckled in subpackage one by one and gets well and be buckled with on the bottle of plug, and dog will
Aluminium lid rolls tightly, delivers to lamp inspection desk, sends into packaging process after lamp inspection is qualified, after packaging process labeling, through mounted box cartonning of examining goods,
Joint sealing is finished product.
Embodiment 5 prepares cefamandole nafate for injection of the present invention, specification: 1.0g
Prescription:
Preparation method:
Aseptically, bottle washing procedure is through by cillin bottle purified water immersion → ultrasonic washing → purified water shower → ultrafiltration
After water shower → water for injection shower, automatically in tunnel oven, tunnel oven have the good casing of insulation, conveyer belt,
Add heat pipe and laminar flow cleaning system composition, bottle on the conveyor belt, preheated rear 320 DEG C of high temperature sterilizing, cooling in more than 5 minutes
To less than 40 DEG C, conveyer belt it is automatically fed into subpackage clean area, for subpackage；Plug is slightly washed through ultrasound wave circulation and purified water
→ purified water and ultrasound wave fine purifiation → water for injection fine purifiation → pure steam sterilization → evacuation heat-wind circulate drying → be cooled to 40 DEG C with
Down for subpackage button plug；Racking machine uses screw rod subpackage, and computer controls impulse ratio, quantitatively, by the head of preparation in embodiment 2
Spore polyester in Meng sodium compound sterile raw material pours into bottle, uses analytical balance selective examination loading amount, bales catch plug；Buckle well the cillin bottle of plug,
Delivering to roll lid operation, aluminium lid is screened by Cover-rolling machine by oscillator, is buckled in subpackage one by one and gets well and be buckled with on the bottle of plug, and dog will
Aluminium lid rolls tightly, delivers to lamp inspection desk, sends into packaging process after lamp inspection is qualified, after packaging process labeling, through mounted box cartonning of examining goods,
Joint sealing is finished product.
Embodiment 6 prepares cefamandole nafate for injection of the present invention, specification: 2.0g
Prescription:
Preparation method:
Aseptically, bottle washing procedure is through by cillin bottle purified water immersion → ultrasonic washing → purified water shower → ultrafiltration
After water shower → water for injection shower, automatically in tunnel oven, tunnel oven have the good casing of insulation, conveyer belt,
Add heat pipe and laminar flow cleaning system composition, bottle on the conveyor belt, preheated rear 320 DEG C of high temperature sterilizing, cooling in more than 5 minutes
To less than 40 DEG C, conveyer belt it is automatically fed into subpackage clean area, for subpackage；Plug is slightly washed through ultrasound wave circulation and purified water
→ purified water and ultrasound wave fine purifiation → water for injection fine purifiation → pure steam sterilization → evacuation heat-wind circulate drying → be cooled to 40 DEG C with
Down for subpackage button plug；Racking machine uses screw rod subpackage, and computer controls impulse ratio, quantitatively, by the head of preparation in embodiment 3
Spore polyester in Meng sodium compound sterile raw material pours into bottle, uses analytical balance selective examination loading amount, bales catch plug；Buckle well the cillin bottle of plug,
Delivering to roll lid operation, aluminium lid is screened by Cover-rolling machine by oscillator, is buckled in subpackage one by one and gets well and be buckled with on the bottle of plug, and dog will
Aluminium lid rolls tightly, delivers to lamp inspection desk, sends into packaging process after lamp inspection is qualified, after packaging process labeling, through mounted box cartonning of examining goods,
Joint sealing is finished product.
Product prepared by the present invention, its mobility, dissolubility, stability relatively commercially available product is all significantly increased.
The study on the stability contrast test of comparative experimental example 1 Cefamandole nafate compounds of the present invention
The cefamandole according to (Chinese Pharmacopoeia two annex XIX C of version in 2010) relevant regulations prepared by the embodiment of the present invention
Ester sodium compound and comparative sample have carried out accelerated test.Take respectively each embodiment 1～3 and commercially available Mandokef sodium raw materials fit
Amount, simulation listing packaging, place 6 months under the conditions of temperature 40 DEG C ± 2 DEG C, relative humidity are 75% ± 5%, respectively at
0th, 1,2,3,6 the end of month are separately sampled, to sample property, clarity of solution, loss on drying, have related substance, content
Equistability inspection target is measured and record, and concrete data see table 1:
Table 1 embodiment 1～3 and the accelerated test result table of comparative sample
Above result of the test shows: under simulation listing terms of packing, embodiment 1～3 and comparative sample temperature 40 DEG C ±
2 DEG C, relative humidity be place 6 months under the conditions of 75% ± 5% after, every Testing index has no significant change, all at regulation model
In enclosing, illustrate that above-mentioned sample is respectively provided with good stability.But after embodiment 1～3 sample is placed 6 months relative to comparative sample
Have related substance and changes of contents amplitude less, illustrate in terms of stability, Cefamandole nafate compounds of the present invention is advantageously.
Additionally, from upper table data it can also be seen that, Cefamandole nafate compounds of the present invention have related substance (include single maximum contaminant and
Total impurities) less than comparative sample, content then higher than comparative sample, illustrates Cefamandole nafate compounds impurity content of the present invention
Less, purity is higher, more can ensure its pharmaceutical preparation efficacy and saferry in clinical practice.
The mobility of comparative experimental example 2 Cefamandole nafate compounds of the present invention compares
Angle of repose is the easiest method of inspection powder fluidity quality, and angle of repose is the least, illustrates that frictional force is the least, mobility
The best.This test uses injection method (fixed funnel method) to measure embodiment 1～3 and the angle of repose of commercially available Mandokef sodium raw materials.
Pour testing sample into funnel so that it is fall into disc centre lightly, equably, form a cone, when material is from powder body
Stopping charging when hypotenuse freely falls along disk border, measure angle of repose with protractor, measurement result is shown in Table 2.
Measurement result angle of repose of table 2 Cefamandole nafate compounds
Embodiment 1～3, namely Cefamandole nafate compounds of the present invention is can be seen that by the result of the test of upper table 2, its
The angle of repose of powder is less than 35 degree, shows good fluidity, can meet the need for liquidity in production process, be suitably applied production
Pharmaceutical preparation and storage transport；And the angle of repose of commercially available Mandokef sodium raw materials is more than 40 degree, mobility is poor, cannot meet
Production requirement, is not suitable for preparing pharmaceutical preparation；Therefore Cefamandole nafate compounds of the present invention and commercially available Mandokef
Sodium raw materials is compared, and its mobility of particle is more preferable, more can meet Production requirement.
Comparative experimental example 3 study on the stability
The embodiment of the present invention 4, embodiment 5 and the sample prepared by embodiment 6 and cefamandole nafate for injection commercially available product A, B
Being accelerated test, accelerated test condition is under conditions of temperature 40 ± 2 DEG C, relative humidity 75 ± 5%, places 3 months.Can
See that foreign body, content, detection method about thing and polymer are official method (Chinese Pharmacopoeia 2010 version two), result
It is shown in Table 2.
Table 2 accelerated test
From table 2: compared with commercially available product A, commercially available product B, the sample size prepared by embodiment of the present invention 4-6 is higher,
Relevant thing is lower, and does not contains polymeric impurities.Sample size after 3 months accelerated tests, prepared by embodiment 4-6
Reducing slower, content is all more than 99%, and relevant thing increases slower, about the total miscellaneous content of thing all below 2%, and not
Polymeric impurities, " visible foreign matters " item passed examination occur, there is not precipitation, illustrates that dissolubility is fine in solution；And commercially available product A
Also complying with quality standard, but content decline and relevant thing and polymer increase the most quickly, content is only 96.6%, and relevant thing is
3.44%, polymer is 0.04%, " visible foreign matters " item passed examination；And commercially available product B is when accelerating 2 months, matter occurs the most
Measuring underproof situation, content is less than 95%, and the relevant total miscellaneous content of thing is more than 3.5%, and " visible foreign matters " item checks defective, molten
There is precipitation in liquid, has crystallization, illustrates that dissolubility is bad.Result above shows, the sample prepared by embodiment of the present invention 4-6
The stability of product is more preferable, and dissolubility is more preferable.
The embodiment of the present invention 4, embodiment 5 and the sample prepared by embodiment 6 and cefamandole nafate for injection commercially available product A, B
It is dissolved in 0.9% sodium chloride injection respectively, is placed at lucifuge cool place, measure 72 hours interior stability datas.Visible foreign matters,
Content, detection method about thing and polymer are official method (Chinese Pharmacopoeia 2010 version two), the results are shown in Table 3.
Table 3 embodiment 4-6, comparative example 1 and the study on the stability of the configured solution of commercially available product A
From data above, embodiment 4, embodiment 5 and sample relatively commercially available product A prepared by embodiment 6 and commercially available product B
After being configured to transfusion, the stability placed at lucifuge cool place is greatly improved, after placing 72 hours, and embodiment 4, embodiment
5 and embodiment 6 prepared by the transfusion that is made into of sample still conform to the requirement of quality standard, and relevant thing is less than 2%, and content is high
In 98%, not containing polymeric impurities, solution is clarified；And the transfusion that commercially available product A is made into is placed into 48 at lucifuge cool place
The little requirement also being compliant with quality standard constantly, is placed into 72 little the most undesirable constantly, and content is 93.7%, and relevant thing is
3.60%, polymer is 0.04%, solutions turbid；And the transfusion that commercially available product B is made into is placed into 24 hours at lucifuge cool place
Time, the most slightly there is not meeting require that of quality standard, relevant thing is 3.51%, and content is 95.3%, and polymer is
0.06%, solution becomes turbid.
As can be seen here, the cefamandole nafate for injection that the present invention provides, relevant thing (the most miscellaneous) is lower, non-polymer, effectively
Component content is higher, and preparation stability is greatly improved, and after being made into injection, dissolubility is good simultaneously, can stablize 72 hours with
On, substantially prolongs standing time, solve the instability problem occurred when this drug solution is placed at lucifuge cool place,
There is obvious effect, provide preferably selection for clinical practice.
Above-described embodiment is only for illustrating technology design and the advantage of the present invention, and the present invention can also have other variation, as
As it is known to those skilled in the art that above-described embodiment functions only as the exemplary role in foregoing invention protection domain, to this area
For those of ordinary skill, also having a lot of conventional deformation and other embodiments in the protection domain that the present invention is limited, these become
Within the protection domain that shape and embodiment all will await the reply in the present invention.
Claims (4)
1. Cefamandole nafate compounds, it is characterised in that its X-ray powder diagram of described Cefamandole nafate compounds
The angle of diffraction 2 θ is 4.86,10.77,11.44,14.75,15.15,15.48,17.09,18.25,19.37,21.43,21.74,
At 22.95,24.55,24.86,26.83 and 31.21 ± 0.2 °, there is characteristic peak；The differential of described Cefamandole nafate compounds is swept
Retouch calorimeter collection of illustrative plates, at 80～100 DEG C, there is endothermic peak, at 198～202 DEG C, there is fusing endothermic peak, maximum heat absorption melt temperature
It it is 198 DEG C；The thermogravimetric curve TGA collection of illustrative plates of described Cefamandole nafate compounds shows, between room temperature to 220 DEG C, and material
Weightlessness is not had before decomposition.
2. the method preparing Cefamandole nafate compounds as claimed in claim 1, it is characterised in that include walking as follows
Rapid:
In methyl tertiary butyl ether(MTBE) and cefamandole nafate dissolving crude product is warmed to 40～50 DEG C, and the acetum with 30% adjusts pH
It is worth to 5.0～6.0, in 10 minutes, adds dimethyl sulfoxide, solution is kept 10 minutes at 40～50 DEG C, add methyl
Acrylic acid cooling crystallization, filters, and 60～70 DEG C are dried, obtain Cefamandole nafate compounds；Described cefamandole nafate crude product
The weight g/ volume ml ratio of consumption and methyl tertiary butyl ether(MTBE) consumption be 1: 5～10；The consumption of described dimethyl sulfoxide and methyl
The volume ratio of tertbutyl ether consumption is 0.02～0.04: 1；The consumption of described methacrylic acid and the body of methyl tertiary butyl ether(MTBE) consumption
Long-pending ratio is 0.4～0.6: 1；-5～-10 DEG C of crystallizes it are cooled to after methacrylic acid adding.
3. cefamandole nafate for injection, specification is that 1.0g/ props up, 1.5g/ props up, 2.0g/ props up, it is characterised in that it is wanted by right
Ask being prepared from of the Cefamandole nafate compounds described in 1.
4. the method for the cefamandole nafate for injection prepared described in claim 3, it is characterised in that comprise the steps:
Aseptically, bottle washing procedure is through by cillin bottle purified water immersion → ultrasonic washing → purified water shower → ultrafiltration
After water shower → water for injection shower, automatically in tunnel oven, tunnel oven have the good casing of insulation, conveyer belt,
Add heat pipe and laminar flow cleaning system composition, bottle on the conveyor belt, preheated rear 320 DEG C of high temperature sterilizing, cooling in more than 5 minutes
To less than 40 DEG C, conveyer belt it is automatically fed into subpackage clean area, for subpackage；Plug is slightly washed through ultrasound wave circulation and purified water
→ purified water and ultrasound wave fine purifiation → water for injection fine purifiation → pure steam sterilization → evacuation heat-wind circulate drying → be cooled to 40 DEG C with
Down for subpackage button plug；Racking machine uses screw rod subpackage, and computer controls impulse ratio, quantitatively, by Cefamandole nafate compounds
Sterile raw material pours into bottle, uses analytical balance selective examination loading amount, bales catch plug；Buckle well the cillin bottle of plug, deliver to roll lid operation,
Aluminium lid is screened by Cover-rolling machine by oscillator, is buckled in subpackage one by one and gets well and be buckled with on the bottle of plug, and aluminium lid is rolled tightly by dog, delivers to
Lamp inspection desk, sends into packaging process after lamp inspection is qualified, and after packaging process labeling, through mounted box cartonning of examining goods, joint sealing is finished product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610238043.2A CN105713013A (en) | 2016-04-17 | 2016-04-17 | Cefamandole nafate compound and cefamandole nafate for injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610238043.2A CN105713013A (en) | 2016-04-17 | 2016-04-17 | Cefamandole nafate compound and cefamandole nafate for injection |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104844625A (en) * | 2015-05-08 | 2015-08-19 | 天津大学 | Cefamandole nafate new crystal form and crystallization preparing method thereof |
| CN104844626A (en) * | 2015-05-08 | 2015-08-19 | 天津大学 | Cefamandole nafate new crystal form and crystallization preparing method thereof |
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| CN104844625A (en) * | 2015-05-08 | 2015-08-19 | 天津大学 | Cefamandole nafate new crystal form and crystallization preparing method thereof |
| CN104844626A (en) * | 2015-05-08 | 2015-08-19 | 天津大学 | Cefamandole nafate new crystal form and crystallization preparing method thereof |
Non-Patent Citations (1)
| Title |
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| 张颖: "头孢孟多酯钠制备工艺的改进", 《海峡药》 * |
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Application publication date: 20160629 |