CN107007554A - Ampicillin Sodium For Injection sulbactam production technology - Google Patents
Ampicillin Sodium For Injection sulbactam production technology Download PDFInfo
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- CN107007554A CN107007554A CN201710402963.8A CN201710402963A CN107007554A CN 107007554 A CN107007554 A CN 107007554A CN 201710402963 A CN201710402963 A CN 201710402963A CN 107007554 A CN107007554 A CN 107007554A
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- Prior art keywords
- sulbactam
- sodium
- ampicillin
- purity
- ampicillin sodium
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
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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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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of Ampicillin Sodium For Injection sulbactam production technology, comprise the following steps：The ampicillin sodium of high-purity and the sulbactam of high-purity are prepared respectively；57 parts of ampicillin sodium, 1 part of the sulbactam of step (1) preparation are weighed, is well mixed under nitrogen protection using in Mixers with Multi-direction Movement, ampicillin sodium and sulbactam sodium then is mixed into powder is distributed into bottle.The Ampicillin Sodium For Injection sulbactam stability that is prepared by the technique is good, purity is high, be not easy allergy.
Description
Technical field
The present invention relates to medicine preparation field, and in particular to a kind of Ampicillin Sodium For Injection sulbactam production technology.
Background technology
Ampicillin sodium and sulbactam sodium is a kind of injecting drug use medically.Alias has that Sultamicillin, excellent power are new, relax ammonia
Newly, unasyn, ampicillin sodium-sulbactam sodium, ampicillin-Sulbactam.Its antibacterial action mechanism is identical with benzyl penicillin, be by with bacterium master
Want PBP to combine, disturb the synthesis of bacteria cell wall and play antibacterial action.Its action character is wide spectrum, intolerant to green grass or young crops
Mycin enzyme.Suitable for the respiratory tract infection caused by treatment sensitive bacteria, including beta-lactamase-producing strain, liver and gall infection, secrete
Urinary system infection, skin soft-tissue infection.Treat aerobic bacteria and anaerobic bacteria mixed infection, particularly abdominal cavity infection and pelvic infection
Deng.
But ampicillin sodium and sulbactam sodium is unstable in production and storage process, impurity is readily incorporated, for example, is produced
During have in residual solvent, storage process and occur degraded and produce other polymers etc., clinically medication can draw these impurity
The adverse reactions such as allergy are played, and drug safety is produced and had a strong impact on, are unfavorable for clinically safe medication.
The content of the invention
In order to solve the above-mentioned technical problem, the present invention discloses a kind of Ampicillin Sodium For Injection sulbactam production technology,
The Ampicillin Sodium For Injection sulbactam stability that is prepared by the technique is good, purity is high, be not easy allergy.
The present invention is achieved through the following technical solutions：
Ampicillin Sodium For Injection sulbactam production technology, comprises the following steps：
(1) ampicillin sodium of high-purity and the sulbactam of high-purity are prepared respectively；
(2) 5-7 parts of ampicillin sodium, 1 part of the sulbactam of step (1) preparation are weighed, under nitrogen protection using multidirectional
It is well mixed in movement mixer, ampicillin sodium and sulbactam sodium then is mixed into powder is distributed into bottle.
The present invention is mixed using the ampicillin sodium and sulbactam by refined purification, and is protected during mixing in nitrogen
Shield is lower to be carried out, it is to avoid the ampicillin sodium of high-purity and sulbactam oxidation by air reaction, it is ensured that its stability and purity, is kept away
Exempt from user's allergy, improve the security of Ampicillin Sodium For Injection sulbactam.
Wherein, in step (1), the concrete technology for preparing the ampicillin sodium of high-purity is：Ampicillin is added to
In pure water, triethylamine is then added in pure water, ampicillin amine salt solution is obtained, carbonic acid then is added dropwise in ampicillin amine salt
Sodium, and be stirred continuously 40-50min, is added dropwise sodium carbonate after completion of the reaction, successively suction filtration, wash and be dried to obtain high purity ammonia
Benzyl XiLin sodium crystal.
In step (1), the concrete technology for preparing high-purity sulbactam is：
1) sulbactam crude product is prepared using sulbactam and anhydrous sodium acetate；
2) sulbactam crude product is dissolved in purified water, adds hydrochloric acid regulation PH, stirring separates out insoluble matter, and filtration washing is obtained
To solid, obtained solid is dissolved with ethyl acetate, adsorbed with polymeric adsorbent, then machine-washed by the use of ethyl acetate as elution
De- purifying, collects eluent, and it is 5-6 that eluent is adjusted into PH with 0.15mol/L sodium bicarbonate solution, separates out solid, centrifugation
After wash, the vacuum dried sulbactam for obtaining high-purity.
Wherein, step 2) in, sulbactam crude product is dissolved in purified water, adds hydrochloric acid regulation PH to 2.5-3.0.Vacuum is done
Dry temperature is 50-65 DEG C.The weight of the ethyl acetate is 15 times of sulbactam crude product.
The present invention compared with prior art, has the following advantages and advantages：
Ampicillin Sodium For Injection sulbactam production technology of the present invention, using the ampicillin sodium by refined purification and
Sulbactam is mixed, and is carried out under nitrogen protection during mixing, it is to avoid the ampicillin sodium and sulbactam quilt of high-purity
Air oxidation reaction, it is ensured that its stability and purity, it is to avoid user's allergy, improves Ampicillin Sodium For Injection sulbactam
Security.
Embodiment
For the object, technical solutions and advantages of the present invention are more clearly understood, with reference to embodiment, to present invention work
Further to describe in detail, exemplary embodiment and its explanation of the invention is only used for explaining the present invention, is not intended as to this
The restriction of invention.
Embodiment 1
Ampicillin Sodium For Injection sulbactam production technology of the present invention, comprises the following steps：
(1) first, ampicillin is added in pure water, triethylamine is then added in pure water, obtain ampicillin amine
Salting liquid, is then added dropwise sodium carbonate in ampicillin amine salt, and is stirred continuously 40min, and sodium carbonate is added dropwise after completion of the reaction, according to
Secondary suction filtration, wash and be dried to obtain high-purity ampicillin sodium crystal, secondly, prepared using sulbactam and anhydrous sodium acetate
Sulbactam crude product, finally, sulbactam crude product is dissolved in purified water, adds hydrochloric acid regulation PH to 3.0, stirring separates out insoluble
Thing, filtration washing obtains solid, and the obtained solid ethyl acetate of 15 times of weight is dissolved, adsorbed with polymeric adsorbent, then
It is purified by flash by the use of ethyl acetate as washing and dehydrating integrated machine, collects eluent, eluent is adjusted with 0.15mol/L sodium bicarbonate solution
It is 6 to save PH, separates out solid, is washed after centrifugation, and the sulbactam of high-purity is obtained through being dried in vacuo at 65 DEG C.
(2) 5 parts of ampicillin sodium, 1 part of the sulbactam of step (1) preparation are weighed, multidirectional fortune is utilized under nitrogen protection
It is well mixed in dynamic mixer, ampicillin sodium and sulbactam sodium then is mixed into powder is distributed into bottle.
Embodiment 2
Ampicillin Sodium For Injection sulbactam production technology of the present invention, comprises the following steps：
(1) first, ampicillin is added in pure water, triethylamine is then added in pure water, obtain ampicillin amine
Salting liquid, is then added dropwise sodium carbonate in ampicillin amine salt, and is stirred continuously 50min, and sodium carbonate is added dropwise after completion of the reaction, according to
Secondary suction filtration, wash and be dried to obtain high-purity ampicillin sodium crystal, secondly, prepared using sulbactam and anhydrous sodium acetate
Sulbactam crude product, finally, sulbactam crude product is dissolved in purified water, adds hydrochloric acid regulation PH to 2.5, stirring separates out insoluble
Thing, filtration washing obtains solid, and the obtained solid ethyl acetate of 15 times of weight is dissolved, adsorbed with polymeric adsorbent, then
It is purified by flash by the use of ethyl acetate as washing and dehydrating integrated machine, collects eluent, eluent is adjusted with 0.15mol/L sodium bicarbonate solution
It is 5 to save PH, separates out solid, is washed after centrifugation, and the sulbactam of high-purity is obtained through being dried in vacuo at 50 DEG C.
(2) 7 parts of ampicillin sodium, 1 part of the sulbactam of step (1) preparation are weighed, multidirectional fortune is utilized under nitrogen protection
It is well mixed in dynamic mixer, ampicillin sodium and sulbactam sodium then is mixed into powder is distributed into bottle.
Embodiment 3
Ampicillin Sodium For Injection sulbactam production technology of the present invention, comprises the following steps：
(1) first, ampicillin is added in pure water, triethylamine is then added in pure water, obtain ampicillin amine
Salting liquid, is then added dropwise sodium carbonate in ampicillin amine salt, and is stirred continuously 45min, and sodium carbonate is added dropwise after completion of the reaction, according to
Secondary suction filtration, wash and be dried to obtain high-purity ampicillin sodium crystal, secondly, prepared using sulbactam and anhydrous sodium acetate
Sulbactam crude product, finally, sulbactam crude product is dissolved in purified water, adds hydrochloric acid regulation PH to 3.0, stirring separates out insoluble
Thing, filtration washing obtains solid, and the obtained solid ethyl acetate of 15 times of weight is dissolved, adsorbed with polymeric adsorbent, then
It is purified by flash by the use of ethyl acetate as washing and dehydrating integrated machine, collects eluent, eluent is adjusted with 0.15mol/L sodium bicarbonate solution
It is 6 to save PH, separates out solid, is washed after centrifugation, and the sulbactam of high-purity is obtained through being dried in vacuo at 60 DEG C.
(2) 6 parts of ampicillin sodium, 1 part of the sulbactam of step (1) preparation are weighed, multidirectional fortune is utilized under nitrogen protection
It is well mixed in dynamic mixer, ampicillin sodium and sulbactam sodium then is mixed into powder is distributed into bottle.
Above-described embodiment, has been carried out further to the purpose of the present invention, technical scheme and beneficial effect
Describe in detail, should be understood that the embodiment that the foregoing is only the present invention, be not intended to limit the present invention
Protection domain, within the spirit and principles of the invention, any modification, equivalent substitution and improvements done etc. all should be included
Within protection scope of the present invention.
Claims (6)
1. Ampicillin Sodium For Injection sulbactam production technology, it is characterised in that comprise the following steps：
(1) ampicillin sodium of high-purity and the sulbactam of high-purity are prepared respectively；
(2) 5-7 parts of ampicillin sodium, 1 part of the sulbactam of step (1) preparation are weighed, Multidirectional motion is utilized under nitrogen protection
It is well mixed in mixer, ampicillin sodium and sulbactam sodium then is mixed into powder is distributed into bottle.
2. Ampicillin Sodium For Injection sulbactam production technology according to claim 1, it is characterised in that step (1)
In, the concrete technology for preparing the ampicillin sodium of high-purity is：Ampicillin is added in pure water, then added in pure water
Enter triethylamine, obtain ampicillin amine salt solution, sodium carbonate then is added dropwise in ampicillin amine salt, and be stirred continuously 40-
50min, be added dropwise sodium carbonate after completion of the reaction, successively suction filtration, wash and be dried to obtain high-purity ampicillin sodium crystal.
3. Ampicillin Sodium For Injection sulbactam production technology according to claim 1, it is characterised in that step (1)
In, the concrete technology for preparing high-purity sulbactam is：
1) sulbactam crude product is prepared using sulbactam and anhydrous sodium acetate；
2) sulbactam crude product is dissolved in purified water, adds hydrochloric acid regulation PH, stirring separates out insoluble matter, and filtration washing is consolidated
Body, obtained solid is dissolved with ethyl acetate, adsorbed with polymeric adsorbent, is then eluted by the use of ethyl acetate as washing and dehydrating integrated machine pure
Change, collect eluent, it is 5-6 that eluent is adjusted into PH with 0.15mol/L sodium bicarbonate solution, separates out solid, is washed after centrifugation
Wash, the vacuum dried sulbactam for obtaining high-purity.
4. Ampicillin Sodium For Injection sulbactam production technology according to claim 3, it is characterised in that step 2)
In, sulbactam crude product is dissolved in purified water, adds hydrochloric acid regulation PH to 2.5-3.0.
5. Ampicillin Sodium For Injection sulbactam production technology according to claim 3, it is characterised in that step 2)
In, vacuum drying temperature is 50-65 DEG C.
6. Ampicillin Sodium For Injection sulbactam production technology according to claim 3, it is characterised in that step 2)
In, the weight of the ethyl acetate is 15 times of sulbactam crude product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710402963.8A CN107007554A (en) | 2017-06-01 | 2017-06-01 | Ampicillin Sodium For Injection sulbactam production technology |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710402963.8A CN107007554A (en) | 2017-06-01 | 2017-06-01 | Ampicillin Sodium For Injection sulbactam production technology |
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| CN107007554A true CN107007554A (en) | 2017-08-04 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201710402963.8A Pending CN107007554A (en) | 2017-06-01 | 2017-06-01 | Ampicillin Sodium For Injection sulbactam production technology |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114796131A (en) * | 2022-05-09 | 2022-07-29 | 四川制药制剂有限公司 | Preparation method of ampicillin sodium for injection |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103301131A (en) * | 2013-06-17 | 2013-09-18 | 四川制药制剂有限公司 | Preparation method of piperacillin sodium sulbactam sodium for injection |
| CN104644629A (en) * | 2015-01-27 | 2015-05-27 | 华北制药股份有限公司 | Ampicillin sodium sulbactam sodium preparation for injection and preparation method thereof |
| CN104922678A (en) * | 2015-05-28 | 2015-09-23 | 浙江长典医药有限公司 | Child-type medicinal composition with ampicillin sulbactam sodium and low-sodium carrier |
| CN105520942A (en) * | 2016-01-04 | 2016-04-27 | 四川制药制剂有限公司 | Ampicillin sodium and sulbactam sodium pharmaceutical composition |
-
2017
- 2017-06-01 CN CN201710402963.8A patent/CN107007554A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103301131A (en) * | 2013-06-17 | 2013-09-18 | 四川制药制剂有限公司 | Preparation method of piperacillin sodium sulbactam sodium for injection |
| CN104644629A (en) * | 2015-01-27 | 2015-05-27 | 华北制药股份有限公司 | Ampicillin sodium sulbactam sodium preparation for injection and preparation method thereof |
| CN104922678A (en) * | 2015-05-28 | 2015-09-23 | 浙江长典医药有限公司 | Child-type medicinal composition with ampicillin sulbactam sodium and low-sodium carrier |
| CN105520942A (en) * | 2016-01-04 | 2016-04-27 | 四川制药制剂有限公司 | Ampicillin sodium and sulbactam sodium pharmaceutical composition |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114796131A (en) * | 2022-05-09 | 2022-07-29 | 四川制药制剂有限公司 | Preparation method of ampicillin sodium for injection |
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Application publication date: 20170804 |
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