CN103110643A - Powder injection of drug composition of ceftazidime for injection - Google Patents
Powder injection of drug composition of ceftazidime for injection Download PDFInfo
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- CN103110643A CN103110643A CN2013100738389A CN201310073838A CN103110643A CN 103110643 A CN103110643 A CN 103110643A CN 2013100738389 A CN2013100738389 A CN 2013100738389A CN 201310073838 A CN201310073838 A CN 201310073838A CN 103110643 A CN103110643 A CN 103110643A
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- Prior art keywords
- ceftazidime
- metronidazole
- injection
- lipid microsphere
- pharmaceutical composition
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- 229960000484 ceftazidime Drugs 0.000 title claims abstract description 50
- NMVPEQXCMGEDNH-TZVUEUGBSA-N ceftazidime pentahydrate Chemical group O.O.O.O.O.S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC(C)(C)C(O)=O)C=2N=C(N)SC=2)CC=1C[N+]1=CC=CC=C1 NMVPEQXCMGEDNH-TZVUEUGBSA-N 0.000 title claims abstract description 50
- 239000000203 mixture Substances 0.000 title claims abstract description 41
- 238000002347 injection Methods 0.000 title claims abstract description 32
- 239000007924 injection Substances 0.000 title claims abstract description 32
- 239000000843 powder Substances 0.000 title claims abstract description 23
- 239000003814 drug Substances 0.000 title claims abstract description 17
- 229940079593 drug Drugs 0.000 title claims abstract description 16
- 229960000282 metronidazole Drugs 0.000 claims abstract description 56
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims abstract description 28
- -1 metronidazole lipid Chemical class 0.000 claims abstract description 28
- 239000004005 microsphere Substances 0.000 claims abstract description 28
- 238000002360 preparation method Methods 0.000 claims abstract description 17
- 239000004475 Arginine Substances 0.000 claims abstract description 10
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 10
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
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- 239000003795 chemical substances by application Substances 0.000 claims description 10
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 8
- 229910052782 aluminium Inorganic materials 0.000 claims description 8
- 238000012856 packing Methods 0.000 claims description 8
- 239000003708 ampul Substances 0.000 claims description 7
- 230000001954 sterilising effect Effects 0.000 claims description 7
- 238000004659 sterilization and disinfection Methods 0.000 claims description 6
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 4
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- 238000011068 loading method Methods 0.000 claims description 4
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- 238000005096 rolling process Methods 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 239000008215 water for injection Substances 0.000 claims description 4
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 2
- 239000005642 Oleic acid Substances 0.000 claims description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 230000006837 decompression Effects 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 claims description 2
- 210000004907 gland Anatomy 0.000 claims description 2
- 125000005456 glyceride group Chemical group 0.000 claims description 2
- 239000005457 ice water Substances 0.000 claims description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 2
- 238000003760 magnetic stirring Methods 0.000 claims description 2
- 238000005360 mashing Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 2
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- 241000894006 Bacteria Species 0.000 description 2
- 208000003322 Coinfection Diseases 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229960004261 cefotaxime Drugs 0.000 description 2
- GPRBEKHLDVQUJE-VINNURBNSA-N cefotaxime Chemical compound N([C@@H]1C(N2C(=C(COC(C)=O)CS[C@@H]21)C(O)=O)=O)C(=O)/C(=N/OC)C1=CSC(N)=N1 GPRBEKHLDVQUJE-VINNURBNSA-N 0.000 description 2
- 241000588986 Alcaligenes Species 0.000 description 1
- 102000004452 Arginase Human genes 0.000 description 1
- 108700024123 Arginases Proteins 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 241000588923 Citrobacter Species 0.000 description 1
- 241000193468 Clostridium perfringens Species 0.000 description 1
- 241001478240 Coccus Species 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 241000588697 Enterobacter cloacae Species 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 241000194033 Enterococcus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 241000588650 Neisseria meningitidis Species 0.000 description 1
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- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
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- 229940121375 antifungal agent Drugs 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
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- 230000001580 bacterial effect Effects 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
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- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides powder injection of a drug composition of ceftazidime for injection, relating to the fields of pharmaceutical preparations and preparation methods and mainly solving the problems that single preparations of ceftazidime and metronidazole in the prior art have great dosages, poor treatment effects after being combined and big side effects. The drug composition comprises main drugs such as ceftazidime and metronidazole lipid microspheres and an auxiliary material arginine, wherein the weight ratio of ceftazidime to metronidazole lipid microspheres is (100:3)-(100:10); the weight ratio of ceftazidime to arginine is 100:27; and the weight of the metronidazole lipid microspheres is based on metronidazole. The drug composition is prepared into powder injection. The pH value of water solution of the drug composition is 5.0-7.0. The powder injection of the drug composition provided by the invention not only has high curative effect but also can reduce the dosage of metronidazole by over 80%, thus greatly reducing or avoiding the toxic and side effects, especially gastrointestinal reactions including nausea, emesis, anorexia, abdominal cramp and neurotoxicity, of metronidazole and further reducing the occurrence rate of adverse reactions.
Description
Technical field:
The present invention relates to pharmaceutical preparation and preparation method field, relate in particular to a kind of ceftazidime medicinal composition for injection injectable powder and preparation method thereof.
Background technology:
Cefotaxime is third generation cephalosporin, and has a broad antifungal spectrum has powerful activity to gram-negative bacterias such as enterobacteriaceae lactobacteriaceae such as escherichia coli, proteus mirabilis, Klebsiella and Salmonellas.Proteus vulgaris and citrobacter genus also there is good action.Enterobacter cloacae, clostridium perfringen are compared drug resistance to this product.This product to pseudomonas aeruginosa and Bacillus alcaligenes without antibiotic activity.Cefotaxime all has powerful effect to hemophilus influenza, Diplococcus gonorrhoeae (comprise and produce the beta lactamase strain), Neisseria meningitidis and moraxelle catarrhalis etc.This product is relatively poor to the antibacterial activity of staphylococcus aureus, and strong to the activity of the gram positive coccus such as Hemolytic streptococcus, streptococcus pneumoniae, Enterococcus is to this product drug resistance.
1972, Tally found that first metronidazole has the effect of whole body anaerobe resistant, and was defined as the drug of first choice of anti anaerobic bacteria infection by World Health Organization (WHO) in 1978.In clinical extensive use, its purposes is widened day by day along with first nitre, and its advantage is: the scope of anaerobe resistant is wide, and sterilizing power is strong, and general avirulence has no drug resistance.It has tablet, injection, suppository, compound preparation, can be for oral, quiet notes and anus plug, also can be applied to intravenously administrable with other multiple antibacterials preparation, so, the requisite a kind of curative of clinical departments become.Recently studying its mechanism of action is, answers by its reduzate and bacterial cell DNA antisense, disturbs growth, the breeding of antibacterial, last kill bacteria.
Untoward reaction appears in nearly 15-30% case clinically, and is the most common with digestive tract reaction, comprises nauseating, vomiting, inappetence, abdominal colic, generally do not affect treatment; Neurological symptom has headache, dizzy, abnormal, the numb limbs and tense tendons of occasionally feeling, ataxia, polyneuritis etc., and heavy dose can cause tic.In the measles such as minority case generation, flushing, pruritus, cystitis, dysuria, mouth, metallic taste and leukopenia etc., all belong to reversibility, recovers voluntarily after drug withdrawal, and reviewing analysis shows that the main cause that untoward reaction occurs is the overdose medication.
infection in clinical operation usually is accompanied by the mixed infection that contains anaerobe and aerobe, rather than the infection of single anaerobe or aerobe, it is the clinical first-selected medication for the treatment of anaerobic infection because of metronidazole, ceftazidime commonly used and metronidazole drug combination contain the MOI of anaerobe for preventing post-operation infection and treatment clinically, but ceftazidime for inj and injection metronidazole are all as single product, during the difference medication, the consumption of metronidazole is very large, the toxic and side effects of metronidazole is very strong, the metronidazole of normal therapeutic dosage can produce digestive tract reaction, the most common comprise nauseating, vomiting, inappetence, abdominal colic and higher neurotoxicity.To this for clinical provide a kind of safe and effective, medicine that toxic and side effects is low is extremely urgent, Given this, proposes the present invention.
Summary of the invention:
Technical problem to be solved by this invention is to overcome the defective of prior art, provide a kind of curative effect high, safe, good stability, the ceftazidime medicinal composition that toxic and side effects is low, this pharmaceutical composition principal agent is: ceftazidime, the metronidazole lipid microsphere, adjuvant is arginine, and said composition can effectively be treated the MOI that contains anaerobe.
Technical problem to be solved by this invention realizes by the following technical solutions.
A kind of ceftazidime medicinal composition, it is characterized in that, the principal agent of this pharmaceutical composition is ceftazidime and metronidazole lipid microsphere, adjuvant is arginine, the weight ratio of ceftazidime and metronidazole lipid microsphere is 100:3-100:10, and ceftazidime and arginic weight ratio are 100:27, and wherein the weight of metronidazole lipid microsphere is in metronidazole, this pharmaceutical composition is prepared into powder ampoule agent for injection, and the pH value of the aqueous solution of this pharmaceutical composition is 5.0-7.0.
In this pharmaceutical composition, the preferred weight ratio of ceftazidime and metronidazole lipid microsphere is 100:5, and the weight of metronidazole lipid microsphere is in metronidazole, and the preferred pH value of the aqueous solution of this pharmaceutical composition is 5.8-6.5.
Another object of the present invention is to provide a kind of method that ceftazidime medicinal composition is prepared into powder ampoule agent for injection, it is characterized in that, the concrete steps of the method are:
(1) preparation metronidazole lipid microsphere, this goods mean diameter is less than 120nm, and pH value is between 5.8-6.5, and the absolute value of Zeta-potential is greater than 20mV.Envelop rate is more than 80%.
The crude drug component of preparation metronidazole lipid microsphere is:
The step of preparation metronidazole lipid microsphere is:
A) glycerol for injection and the poloxamer F-68 with recipe quantity is dissolved in water for injection, be placed in 80 ℃ of water bath with thermostatic control magnetic stirring apparatuss and be stirred to whole dissolvings, make mixture A, the injection water yield can be with abundant fused the getting final product of glycerol for injection and poloxamer F-68;
B) recipe quantity oleic acid is added in the oil phase that is consisted of by long-chain fat acid glyceride and medium chain length fatty acid triglyceride, forms and mix oil phase;
C) fabaceous lecithin and the metronidazole with recipe quantity adds in dehydrated alcohol 200ml, is stirred to fabaceous lecithin and metronidazole under 80 ℃ all after dissolving, and decompression volatilizes dehydrated alcohol, then adds the mixing oil phase, stirs and makes mixture B;
D) mixture A is added in mixture B, be placed in the 8000r/min of high-speed tissue mashing machine and stir 3 times, each 3min;
E) regulate pH value to 5.8-6.5, water for injection is settled to 1000ml, adds in high pressure homogenizer 70MPa homogenizing 8 times;
F) bottling, gland, 100 ℃ of sterilization 30min, the rapid cooling of ice-water bath and get final product, standby;
(2) ceftazidime, metronidazole lipid microsphere and arginine are dropped into respectively in proportion in the efficient asymmetric mixer of V-type, mix after 1.5 hours, listen by the aluminum that drain hole is put into after sterilization; Aluminum is listened rolled lid, labeling, packing;
(3) compound with step (2) adds in racking machine, adjusts loading amount according to batch production ordering, is distributed into cillin bottle, buckles butyl rubber plug, namely gets the ceftazidime medicinal composition injectable powder of injection through rolling lid, lamp inspection, packing.
The specification that described ceftazidime medicinal composition is prepared into powder ampoule agent for injection is 0.5g/ bottle, 1.5g/ bottle, 1.0g/ bottle and 2.0g/ bottle, by ceftazidime.
Pharmaceutical composition preparation technology of the present invention is simple, has guaranteed well the growth of related substance in the storage of the stability of active component and finished product.
The present invention is directed to treatment clinically and contain the MOI of anaerobe and propose, a kind of ceftazidime for inj composition powder injection is provided.The every consumption per day of ceftazidime list product preparation adult is the 4g left and right clinically, and the consumption that metronidazole list product preparation is grown up every day is the 2g left and right.in ceftazidime medicinal composition provided by the invention, ceftazidime, metronidazole lipid microsphere (take metronidazole) weight ratio (W/W) is 100:3-100:10, therefore the every consumption per day of ceftazidime is 4g, at twice during administration, the consumption of metronidazole every day is 120mg-400mg, each consumption is 60mg-200mg, be that 4000ml calculates by the normal adult total blood volume, after each administration, blood drug level is 15-50 μ g/ml, and the metronidazole effective blood drug concentration is 2-8 μ g/ml, the metronidazole lipid microsphere has slow releasing function, the effective blood drug concentration time can keep more than 12 hours in vivo.Pharmaceutical composition injectable powder provided by the invention not only has high curative effect thus, and can reduce metronidazole consumption (using more than 80% less), thereby greatly alleviate or avoided the toxic and side effects of metronidazole, digestive tract reaction particularly, comprise nauseating, vomiting, inappetence, abdominal colic and neurotoxicity, more reduced the incidence rate of untoward reaction.
The specific embodiment:
For technological means, creation characteristic that the present invention is realized, reach purpose and effect is easy to understand, below in conjunction with specific embodiment, further set forth the present invention.
For the concordance of guarantee test result, the embodiment of the present invention has been used raw material, adjuvant, cillin bottle and the plug of same batch, and has adopted consistent production technology to prepare the ceftazidime medicinal composition injectable powder of injection.
Embodiment one, ceftazidime for inj composition powder injection are in 1000
Prescription (specification: the 0.5g/ bottle):
Ceftazidime 500g
Metronidazole lipid microsphere (in metronidazole) 25g
Arginine 135g
Preparation technology:
Ceftazidime, metronidazole lipid microsphere and the arginine of recipe quantity are dropped into respectively in the efficient asymmetric mixer of V-type, mix after 1.5 hours, listen by the aluminum that drain hole is put into after sterilization; Aluminum is listened rolled lid, labeling, packing; Again mixed material is added in racking machine, adjust loading amount according to batch production ordering, be distributed into cillin bottle, buckle butyl rubber plug, namely get the ceftazidime medicinal composition injectable powder of injection through rolling lid, lamp inspection, packing.
Embodiment two, ceftazidime for inj composition powder injection are in 1000
Prescription (specification: the 1.0g/ bottle):
Ceftazidime 1000g
Metronidazole lipid microsphere (in metronidazole) 50g
Arginase 12 70g
Preparation technology:
Ceftazidime, metronidazole lipid microsphere and the arginine of recipe quantity are dropped into respectively in the efficient asymmetric mixer of V-type, mix after 1.5 hours, listen by the aluminum that drain hole is put into after sterilization; Aluminum is listened rolled lid, labeling, packing; Again mixed material is added in racking machine, adjust loading amount according to batch production ordering, be distributed into cillin bottle, buckle butyl rubber plug, namely get the ceftazidime medicinal composition injectable powder of injection through rolling lid, lamp inspection, packing.
Clinical data
In the patient who makes a definite diagnosis anaerobe and aerobe (to the aerobe of ceftazidime sensitivity) mixed infection, use A scheme (4 bottles/day of ceftazidime for inj composition powder injections (1.0g/ bottle)) and B scheme (ceftazidime 4g/ day+metronidazole 2g/ day) GP TH, each is organized and divides equally 2 venoclysises every day, and its curative effect and untoward reaction are as follows:
The Comprehensive Clinical curative effect
To curative effect judgement terminal point, total number of cases 98 examples of A scheme group, effective 90 examples, total effective rate is total number of cases 82 examples of 92%, B scheme group, effective 74 examples, total effective rate is 90%.
Adverse effect
Treat in 180 routine cases, the untoward reaction of varying degree appears in totally 30 examples, and the untoward reaction rate is 16.7%, wherein gastrointestinal reaction appears in the routine patient of A scheme group 8, the side effect incidence rate be 8%, B scheme group totally 21 examples the untoward reaction of varying degree appears, the side effect incidence rate is 25.6%.A scheme group adverse reaction rate and degree are all lower than B scheme group.
Above demonstration and described ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and description is only preference of the present invention; be not used for limiting the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.The claimed scope of the present invention is defined by appending claims and equivalent thereof.
Claims (4)
1. ceftazidime medicinal composition, it is characterized in that, the principal agent of this pharmaceutical composition is ceftazidime and metronidazole lipid microsphere, adjuvant is arginine, the weight ratio of ceftazidime and metronidazole lipid microsphere is 100:3-100:10, and ceftazidime and arginic weight ratio are 100:27, and wherein the weight of metronidazole lipid microsphere is in metronidazole, this pharmaceutical composition is prepared into powder ampoule agent for injection, and the pH value of the aqueous solution of this pharmaceutical composition is 5.0-7.0.
2. ceftazidime medicinal composition according to claim 1, it is characterized in that, in this pharmaceutical composition, the preferred weight ratio of ceftazidime and metronidazole lipid microsphere is 100:5, the weight of metronidazole lipid microsphere is in metronidazole, and the preferred pH value of the aqueous solution of this pharmaceutical composition is 5.8-6.5.
3. the described pharmaceutical composition of claim 1 or 2 is prepared into the method for powder ampoule agent for injection, it is characterized in that, the concrete steps of the method are:
(1) preparation metronidazole lipid microsphere
The crude drug component of preparation metronidazole lipid microsphere is:
The step of preparation metronidazole lipid microsphere is:
A) glycerol for injection and the poloxamer F-68 with recipe quantity is dissolved in water for injection, be placed in 80 ℃ of water bath with thermostatic control magnetic stirring apparatuss and be stirred to whole dissolvings, make mixture A, the injection water yield can be with abundant fused the getting final product of glycerol for injection and poloxamer F-68;
B) recipe quantity oleic acid is added in the oil phase that is consisted of by long-chain fat acid glyceride and medium chain length fatty acid triglyceride, forms and mix oil phase;
C) fabaceous lecithin and the metronidazole with recipe quantity adds in dehydrated alcohol 200ml, is stirred to fabaceous lecithin and metronidazole under 80 ℃ all after dissolving, and decompression volatilizes dehydrated alcohol, then adds the mixing oil phase, stirs and makes mixture B;
D) mixture A is added in mixture B, be placed in the 8000r/min of high-speed tissue mashing machine and stir 3 times, each 3min;
E) regulate pH value to 5.8-6.5, water for injection is settled to 1000ml, adds in high pressure homogenizer 70MPa homogenizing 8 times;
F) bottling, gland, 100 ℃ of sterilization 30min, the rapid cooling of ice-water bath and get final product, standby;
(2) ceftazidime, metronidazole lipid microsphere and arginine are dropped into respectively in proportion in the efficient asymmetric mixer of V-type, mix after 1.5 hours, listen by the aluminum that drain hole is put into after sterilization; Aluminum is listened rolled lid, labeling, packing;
(3) compound with step (2) adds in racking machine, adjusts loading amount according to batch production ordering, is distributed into cillin bottle, buckles butyl rubber plug, namely gets the ceftazidime medicinal composition injectable powder of injection through rolling lid, lamp inspection, packing.
4. ceftazidime medicinal composition according to claim 3 is prepared into the method for powder ampoule agent for injection, it is characterized in that: the specification that described ceftazidime medicinal composition is prepared into powder ampoule agent for injection is 0.5g/ bottle, 1.5g/ bottle, 1.0g/ bottle and 2.0g/ bottle, by ceftazidime.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5250236A (en) * | 1991-08-05 | 1993-10-05 | Gasco Maria R | Method for producing solid lipid microspheres having a narrow size distribution |
| CN102875576A (en) * | 2012-10-31 | 2013-01-16 | 苏州致君万庆药业有限公司 | Synthesis of antibiotic ceftazidime, ceftazidime for injection and preparation method of ceftazidime |
-
2013
- 2013-03-08 CN CN2013100738389A patent/CN103110643A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5250236A (en) * | 1991-08-05 | 1993-10-05 | Gasco Maria R | Method for producing solid lipid microspheres having a narrow size distribution |
| CN102875576A (en) * | 2012-10-31 | 2013-01-16 | 苏州致君万庆药业有限公司 | Synthesis of antibiotic ceftazidime, ceftazidime for injection and preparation method of ceftazidime |
Non-Patent Citations (4)
| Title |
|---|
| L.A.M. FERREIRA ET AL: "Vehicle influence on in vitro release of metronidazole:role of w/o/w multiple emulsion", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》, no. 109, 31 December 1994 (1994-12-31), pages 251 - 259 * |
| YUTAKA MIZUSHIMA: "Lipid microspheres (lipid emulsions) as a drug carrier - An overview", 《ADVANCED DRUG DELIVERY REVIEW》, no. 20, 31 December 1996 (1996-12-31), pages 113 - 115 * |
| 冯大林等: "脂质微球给药系统的研究进展", 《现代医药卫生》, vol. 28, no. 7, 15 April 2012 (2012-04-15), pages 1037 - 1039 * |
| 邹明智等: "泰得欣在小儿急性阑尾炎中的应用", 《海南医学》, vol. 16, no. 10, 31 December 2005 (2005-12-31), pages 29 - 30 * |
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