CN101810623A - Ceftazidime medicinal composition for injection and preparation method thereof - Google Patents
Ceftazidime medicinal composition for injection and preparation method thereof Download PDFInfo
- Publication number
- CN101810623A CN101810623A CN200910223919A CN200910223919A CN101810623A CN 101810623 A CN101810623 A CN 101810623A CN 200910223919 A CN200910223919 A CN 200910223919A CN 200910223919 A CN200910223919 A CN 200910223919A CN 101810623 A CN101810623 A CN 101810623A
- Authority
- CN
- China
- Prior art keywords
- ceftazidime
- medicinal composition
- injection
- preparation
- arginine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- NMVPEQXCMGEDNH-TZVUEUGBSA-N ceftazidime pentahydrate Chemical compound 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 205
- 229960000484 ceftazidime Drugs 0.000 title claims abstract description 202
- 239000000203 mixture Substances 0.000 title claims abstract description 74
- 238000002347 injection Methods 0.000 title claims abstract description 60
- 239000007924 injection Substances 0.000 title claims abstract description 60
- 238000002360 preparation method Methods 0.000 title claims abstract description 53
- 239000004475 Arginine Substances 0.000 claims abstract description 50
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 50
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 26
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 26
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 34
- 238000000746 purification Methods 0.000 claims description 30
- KGWHMDCQVDMTNZ-UHFFFAOYSA-N 2-(butylcarbamoylamino)acetic acid Chemical compound CCCCNC(=O)NCC(O)=O KGWHMDCQVDMTNZ-UHFFFAOYSA-N 0.000 claims description 27
- 229960003547 ceftazidime pentahydrate Drugs 0.000 claims description 27
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 25
- 235000006708 antioxidants Nutrition 0.000 claims description 25
- 239000007864 aqueous solution Substances 0.000 claims description 25
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 22
- 230000001954 sterilising effect Effects 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 18
- 235000010265 sodium sulphite Nutrition 0.000 claims description 17
- 239000013078 crystal Substances 0.000 claims description 16
- 239000000706 filtrate Substances 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 12
- 238000012856 packing Methods 0.000 claims description 12
- 238000001556 precipitation Methods 0.000 claims description 12
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 11
- 229930003268 Vitamin C Natural products 0.000 claims description 11
- 239000003513 alkali Substances 0.000 claims description 11
- 238000004140 cleaning Methods 0.000 claims description 11
- 239000011521 glass Substances 0.000 claims description 11
- 238000007689 inspection Methods 0.000 claims description 11
- 238000002372 labelling Methods 0.000 claims description 11
- 238000004659 sterilization and disinfection Methods 0.000 claims description 11
- 235000019154 vitamin C Nutrition 0.000 claims description 11
- 239000011718 vitamin C Substances 0.000 claims description 11
- 238000005303 weighing Methods 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 10
- PWKSKIMOESPYIA-UHFFFAOYSA-N 2-acetamido-3-sulfanylpropanoic acid Chemical compound CC(=O)NC(CS)C(O)=O PWKSKIMOESPYIA-UHFFFAOYSA-N 0.000 claims description 7
- 238000010298 pulverizing process Methods 0.000 claims description 7
- 238000002425 crystallisation Methods 0.000 claims description 6
- 230000008025 crystallization Effects 0.000 claims description 6
- 238000000247 postprecipitation Methods 0.000 claims description 3
- 230000001105 regulatory effect Effects 0.000 claims description 3
- 229920000642 polymer Polymers 0.000 abstract description 41
- 239000002932 luster Substances 0.000 abstract description 16
- 239000003814 drug Substances 0.000 abstract description 14
- 229940079593 drug Drugs 0.000 abstract description 7
- 230000008901 benefit Effects 0.000 abstract description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 12
- 239000005457 ice water Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 11
- 238000003756 stirring Methods 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 8
- 239000006184 cosolvent Substances 0.000 description 8
- 238000004811 liquid chromatography Methods 0.000 description 8
- 238000012360 testing method Methods 0.000 description 7
- 235000013878 L-cysteine Nutrition 0.000 description 6
- 239000004201 L-cysteine Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 230000028016 temperature homeostasis Effects 0.000 description 6
- 238000001291 vacuum drying Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 206010002198 Anaphylactic reaction Diseases 0.000 description 4
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 4
- 230000036783 anaphylactic response Effects 0.000 description 4
- 208000003455 anaphylaxis Diseases 0.000 description 4
- 229960003121 arginine Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 238000006116 polymerization reaction Methods 0.000 description 4
- 229910001415 sodium ion Inorganic materials 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000013558 reference substance Substances 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 239000013638 trimer Substances 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- 206010001526 Air embolism Diseases 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000003825 pressing Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- 206010056519 Abdominal infection Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000031729 Bacteremia Diseases 0.000 description 1
- 206010061695 Biliary tract infection Diseases 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 241000194033 Enterococcus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 206010017964 Gastrointestinal infection Diseases 0.000 description 1
- 241000521257 Hydrops Species 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 241000588650 Neisseria meningitidis Species 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000607764 Shigella dysenteriae Species 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 238000006701 autoxidation reaction Methods 0.000 description 1
- 229920005601 base polymer Polymers 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 208000003167 cholangitis Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 208000019836 digestive system infectious disease Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 210000003725 endotheliocyte Anatomy 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- -1 heart disease Chemical compound 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 206010034674 peritonitis Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 229940007046 shigella dysenteriae Drugs 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 230000029547 smooth muscle hypertrophy Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229910021655 trace metal ion Inorganic materials 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a ceftazidime medicinal composition for injection and a preparation method thereof. The ceftazidime medicinal composition for injection comprises the following components in part by weight: 1 part of ceftazidime, 0.05 to 0.5 part of arginine and 0.0001 to 0.001 part of antioxidant. The ceftazidime medicinal composition for injection provided by the invention has the advantages of good dissolubility, good quality, stable color and luster and low polymer content, and the polymer content cannot be increased due to the increment of storage time, so that the medication safety is improved.
Description
Technical field
The invention belongs to formulation art, be specifically related to a kind of ceftazidime medicinal composition for injection and preparation method thereof.
Background technology
Ceftazidime is a third generation cephalosporin class antibiotic, and antibiotic vigor is stronger, and antimicrobial spectrum is wider, Grain-positive or negative bacterium is all had pretend usefulness.The beta-lactamase that gram positive bacteria, negative bacterium are produced has the stability of height, and this product has strong antibacterial activity to bacillus pyocyaneus, escherichia coli, klebsiella bacillus, Bacillus proteus, enterococcus, salmonella, shigella dysenteriae, Diplococcus gonorrhoeae, Neisseria meningitidis, golden Portugal bacterium, Hemolytic streptococcus, streptococcus pneumoniae and aerobacteria etc.Ceftazidime is applicable to respiratory tract infection, urinary tract infection, skin and soft tissue infection, gastrointestinal, biliary tract and abdominal infection, bone and the infection of joint due to the sensitive organism, dialysis and the infection mitigation treatment of concurrent infection, various operations, and septicemia, bacteremia, peritonitis, meningitis, immune downtrod patient's infection and infectious burn.
Ceftazidime for inj is very extensive in clinical practice because of good efficacy, but ceftazidime this as acidic materials, molecular formula is C
22H
22N
6O
7S
25H
2O, its structural formula is as follows:
Ceftazidime pentahydrate is to use utmost point cephalosporin widely clinically, pH value (3.0-4.0), and the hydrophobicity that tool is certain, be insoluble in acid solution, dissolubility height under the nearly neutrallty condition of pH, and the pH value that is commonly used for normal saline, 5% Glucose Liquid of dissolving, diluent clinically is respectively all slant acidity of (4.5-7.0), (3.2-5.5), adds sodium carbonate as cosolvent in the ceftazidime preparation so all adopt in the past, regulates pH value and is beneficial to the ceftazidime dissolving.
Find that through long-term clinical use sodium carbonate has following shortcoming as cosolvent:
(1) patients such as heart disease, hypertension, nephropathy, hepatic ascites need to limit the absorption of sodium ion, are not suitable for using the preparation that contains sodium ion, can increase patient's drug risk as using with sodium carbonate as the ceftazidime of cosolvent.(2) sodium carbonate is the weak acid strong alkali compound, is dissolved in the acid solution sodium carbonate and can emits carbon dioxide.And ceftazidime, normal saline, the equal slant acidity of 5% Glucose Liquid, so can produce CO as the ceftazidime of cosolvent when the dilution with sodium carbonate
2Gas may pollute medicinal liquid if bleeding is improper, as CO in the infusion process
2Stripping produces bubble and other is entered in the blood samples of patients may form gas embolism, as obstruction appear at the heart, the main blood vessel of brain can cause very big danger to the patient.(3) ceftazidime is unsettled in sodium bicarbonate solution.And being dissolved in acid solution, sodium carbonate can decomposite CO
2So sodium carbonate is stablized influential as cosolvent to ceftazidime.
Be the shortcoming of avoiding sodium carbonate to bring, replace sodium carbonate as the ceftazidime cosolvent, and use in multinational listing such as the U.S., Britain, Germany, Japan, Italy with the organic compound arginine.Existing domestic by first development and production of right overhead Pharmaceutical---ceftazidime (containing arginine) as cosolvent and stabilizing agent.
Arginine is the water-soluble alkali acidic amino acid that human body contains, molecular formula C
6H
14N
4O
2, its isoelectric level pH is 11.15, and its aqueous solution is strong basicity, and is soluble in water, and an amount of arginine scalable ceftazidime pH value of solution increases the ceftazidime dissolubility to neutral.
Arginine has been compared following advantage as cosolvent with sodium carbonate:
(1) arginine stable in properties does not produce CO when dissolving in water
2, or not ceftazidime dissolubility and stability can be do not improved, and the contaminated hydrops of medicinal liquid can be reduced with the ceftazidime effect, and can gas embolism, the medicine safety in utilization increased.
(2) arginine does not contain sodium ion, and the patient that needs restriction sodium ion such as heart disease, hypertension, nephropathy, hepatic ascites are taken in uses safer.
(3) arginine forms arginine/nitric oxide system in the human body effect.Nitric oxide has the vasodilation of adjusting, suppresses the vascular smooth muscle hypertrophy and suppresses the platelet adhesion aggregation capability as a kind of cell messenger molecule.Additional arginine can recover endotheliocyte vasodilation function, reduces hematoblastic gathering, reduces the leukocyte adhesion blood vessel wall, reduces the arteriosclerosis process, and blood circulation is had the improvement effect.
But because ceftazidime is met light, thermally labile, easily produce catabolite, particularly suffer under the situation of high temperature (＞50 ℃), degraded and polyreaction often take place, generate ceftazidime dimer, trimer and polymer or the like polymer, thereby cause active constituents of medicine content to reduce, color and luster is strengthened, and polymeric impurities content raises.In addition, the ceftazidime antibiotic because the resting period is long, also usually makes the medicine active component content reduce, and darkens, and polymer content raises.And polymer content easily makes human body produce anaphylaxis when high.These phenomenons have become the 'bottleneck' restrictions problem of this outstanding kind development.
At present, study the deliquescent problem of ceftazidime on the market mostly, and the solution not good to the problem of ceftazidime color and luster, degraded, polymerization and stability, and, more need the ceftazidime preparation that matter is measured, color and luster is stable clinically except needing the good ceftazidime preparation of dissolubility.
Summary of the invention
Purpose of the present invention just is to overcome above-mentioned defective, provides a kind of not only dissolubility good, and the ceftazidime medicinal composition for injection that quality is good, color and luster is stable.
For achieving the above object, the present invention adopts following technical scheme:
A kind of ceftazidime medicinal composition for injection, wherein, described ceftazidime medicinal composition for injection is composed of the following components:
A kind of ceftazidime medicinal composition for injection is characterized in that: described ceftazidime medicinal composition for injection is made up of following component:
Ceftazidime 1 weight portion
Arginine 0.05-0.5 weight portion
Antioxidant 0.0001-0.001 weight portion.
According to aforesaid ceftazidime medicinal composition for injection, wherein: described ceftazidime medicinal composition for injection is made up of following component:
1 part of ceftazidime
0.1 part of arginine
Antioxidant 0.0001-0.005 weight portion.
According to aforesaid ceftazidime medicinal composition for injection, wherein: described antioxidant is a kind of or its mixture in L-cysteine, sodium sulfite or the vitamin C.
The preparation method of the ceftazidime medicinal composition for injection that another object of the present invention is to provide above-mentioned, not only dissolubility is good to adopt the ceftazidime medicinal composition for injection of this method preparation, and quality is good, color and luster stable.
For achieving the above object, the present invention adopts following technical scheme:
A kind of preparation method of ceftazidime medicinal composition for injection of the present invention, this method method comprises the steps:
1) supplementary material is removed outer package after, dedusting cleaning, the wiping sterilization, it is standby to enter sterilizing room;
2), with ceftazidime, arginine and antioxidant pulverize separately, sieve, standby at clean area;
3) take by weighing step 2 at clean area) resulting ceftazidime, arginine and antioxidant, in the ratio mixing of prescription, survey content and be sub-packed in the glass tube vial after qualified, tamponade, to roll lid, lamp inspection, be up to the standards, labeling, packing are promptly.
Sieving according to the preparation method of aforesaid ceftazidime medicinal composition for injection, wherein, step 2) is to cross 60-100 mesh sieve, preferred 80 mesh sieves.
According to the preparation method of aforesaid ceftazidime medicinal composition for injection, wherein, step 2) temperature of clean area is controlled at 18-26 ℃ described in, and relative humidity is controlled at 45%-65%.
According to the preparation method of aforesaid ceftazidime medicinal composition for injection, wherein, described purification process is carried out purification process or/and after obtaining ceftazidime medicinal composition for injection it is carried out purification process to ceftazidime before being included in and pulverizing.
According to the preparation method of aforesaid ceftazidime medicinal composition for injection, wherein, before pulverizing, ceftazidime is carried out purification process and be: ceftazidime is added in the entry, randomly add acid and make its dissolving, obtain the ceftazidime aqueous solution; PH with alkali or acid adjusting ceftazidime aqueous solution is 1.5-2.5 then, has precipitation to separate out; Remove by filter precipitation, it is 3.5-4.8 that resulting filtrate continues to regulate pH with alkali, and the control temperature is at 0-40 ℃, and the ceftazidime pentahydrate crystal structure is separated out.
According to the preparation method of aforesaid ceftazidime medicinal composition for injection, wherein, removing by filter post precipitation, it is 4.0-4.6 that resulting filtrate is regulated pH with alkali.
Preparation method according to aforesaid ceftazidime medicinal composition for injection, wherein, obtain it being carried out purification process behind the ceftazidime medicinal composition for injection be: ceftazidime added obtain the ceftazidime aqueous solution in the entry, then under 8-12 ℃ temperature, the pH that regulates the ceftazidime aqueous solution with acid is 4.2-4.6, separate out crystal, and in crystallization process, pass through the adding of control acid, make pH remain on 4.2-4.6.
Below be detailed description of the present invention:
On the one hand, the invention provides a kind of stable ceftazidime medicinal composition for injection, this pharmaceutical composition not only dissolubility is good, and quality is good, color and luster stable.
Ceftazidime medicinal composition for injection provided by the present invention is made up of following component:
Ceftazidime 1 weight portion
Arginine 0.05-0.5 weight portion
Antioxidant 0.0001-0.001 weight portion.
Analyzing ceftazidime color and luster of the present invention variation, degraded, polymerization and unsettled main cause may be that the ceftazidime structure is easily oxidized, and the oxygen in the atmosphere is the major reason that causes oxidation of drug, and the general source of the oxygen in the preparation is water and air.Temperature raises, and generally accelerates oxidation reaction speed; Light also can excite oxidation reaction as a kind of radiant energy, quickens the decomposition of medicine, and reaction has remarkable catalytic action to trace metal ion to autoxidation; Humidity and moisture also quicken the oxidation and the decomposition of medicine.But the variation of ceftazidime color and luster, degraded, polymerization and unsettled exact mechanism are also unclear at present.The inventor is surprised to find that adding antioxidant can solve the variation of ceftazidime color and luster, degraded, polymerization and problem of unstable.
The present invention finds that by the screening of prescription consumption when the ceftazidime medicinal composition for injection that is provided was following proportioning, effects such as its stability were better:
1 part of ceftazidime
0.1 part of arginine
Antioxidant 0.0001-0.005 weight portion.
But it not is that any antioxidant can both address this problem that the inventor finds.Suitable antioxidant of the present invention comprises a kind of in L-cysteine, sodium sulfite or the vitamin C or their mixture, preferred L-cysteine or vitamin C or their mixture.Described mixing is meant any two or more the mixture in L-cysteine, sodium sulfite or the vitamin C.
The inventor finds obviously to have improved by the antioxidant described in adding the present invention the stability of ceftazidime, and particularly under the condition of illumination and high humidity, color and luster is stable, and improvement is also arranged under the hot conditions.And not adding the sample of antioxidant, color and luster changes highly significant under its similarity condition.
On the other hand, the invention provides the preparation method of above-mentioned ceftazidime medicinal composition for injection, this method simple possible, not only dissolubility is good to adopt the ceftazidime for inj medicine of this method preparation, and quality is good, color and luster stable.
Preparation method provided by the present invention comprises the steps:
1) supplementary material is removed outer package after, dedusting cleaning, the wiping sterilization, it is standby to enter sterilizing room;
2), with ceftazidime, arginine and antioxidant pulverize separately, sieve, standby at clean area;
3) take by weighing step 2 at clean area) resulting ceftazidime, arginine and antioxidant, in the ratio mixing of prescription, survey content and be sub-packed in the glass tube vial after qualified, tamponade, to roll lid, lamp inspection, be up to the standards, labeling, packing are promptly.
Sieving in the preparation method of the present invention, step 2) is to cross 60-100 mesh sieve, preferred 80 mesh sieves.
In the preparation method of the present invention, step 2) temperature of clean area is controlled at 18-26 ℃ described in, and relative humidity is controlled at 45%-65%.
In the preparation method of the present invention, also comprise purification process in the described preparation method.
Described purification process is carried out purification process or/and after obtaining ceftazidime medicinal composition for injection it is carried out purification process to ceftazidime before being included in and pulverizing.
In some cases, because controlling of production process is improper, resulting ceftazidime pentahydrate, the content of ceftazidime dimer, trimer and polymer or the like polymer is high especially.And polymer content easily makes human body produce anaphylaxis when high.If directly being used for packing, these crude drug ceftazidimes make ceftazidime pharmaceutical preparation, will certainly cause a hidden trouble to health, therefore be necessary further to carry out purification for the ceftazidime crude drug, obtain ceftazidime pentahydrate crystal high-quality, that purity is high, to eliminate the potential danger that polymer causes health.
The present invention finds to carry out purification process earlier before ceftazidime is pulverized, and can obtain ceftazidime pentahydrate high-quality, that purity is high, thereby eliminates the potential danger that polymer causes health.
In addition, because the ceftazidime preparation is in depositing process, particularly suffer under the situation of (＞50 ℃), degraded and polyreaction often take place, generate ceftazidime dimer, trimer and polymer or the like polymer, thereby cause active constituents of medicine content to reduce, color and luster is strengthened, and polymeric impurities content raises.And polymer content easily makes human body produce anaphylaxis when high, so high ceftazidime pharmaceutical preparation also is necessary further to carry out purification for this base polymer impurity content, obtains ceftazidime pharmaceutical preparation high-quality, that purity is high.
In the preparation method of the present invention, described purification process is carried out purification process or/and after obtaining ceftazidime medicinal composition for injection it is carried out purification process to ceftazidime before being included in and pulverizing, and can address the above problem like this.
In the preparation method of the present invention, before pulverizing, ceftazidime is carried out purification process and be: ceftazidime is added in the entry, randomly add acid and make its dissolving, obtain the ceftazidime aqueous solution; PH with alkali or acid adjusting ceftazidime aqueous solution is 1.5-2.5 then, has precipitation to separate out; Remove by filter precipitation, it is 3.5-4.8 that resulting filtrate continues to regulate pH with alkali, and the control temperature is at 0-40 ℃, and the ceftazidime pentahydrate crystal structure is separated out.
Ceftazidime pentahydrate impure, that polymer content is high can adopt method of the present invention, makes with extra care, and obtains pure ceftazidime pentahydrate.Thereby preparation high-quality, the ceftazidime pharmaceutical preparation that purity is high.
In the preparation method of the present invention, removing by filter post precipitation, it is 4.0-4.6 that resulting filtrate is regulated pH with alkali.
In the preparation method of the present invention, obtain it being carried out purification process behind the ceftazidime medicinal composition for injection be: ceftazidime added obtain the ceftazidime aqueous solution in the entry, then under 8-12 ℃ temperature, the pH that regulates the ceftazidime aqueous solution with acid is 4.2-4.6, separate out crystal, and in crystallization process, pass through the sour adding of control, make pH remain on 4.2-4.6.
Utilize said method can obtain the ceftazidime pharmaceutical preparation that dissolubility is good, color and luster stable, quality is good, purity is high.
The present invention has following advantage:
(1) ceftazidime medicinal composition for injection of the present invention has increased antioxidant on the basis of conventional formulation, has obviously improved the stability of ceftazidime, and particularly under the condition of illumination and high humidity, color and luster is stable, and improvement is also arranged under the hot conditions;
(2) adding of antioxidant has also solved in its preparation because the problem of the content of polymer in the ceftazidime medicinal composition for injection of the present invention, and ceftazidime medicinal composition for injection polymer content of the present invention is low, thereby has reduced drug anaphylaxis;
(3) in the method for the present invention the raw material ceftazidime is carried out purification process or/and after obtaining ceftazidime medicinal composition for injection it is carried out purification process, not only solved owing to the high problem of the improper polymer content that causes in the production technology, also solved the ceftazidime preparation and deposited the problem that its polymer content of process increases.
The specific embodiment
In the present invention, according to " Chinese pharmacopoeia (2000 editions, the 171st page to 172 pages, Chemical Industry Press) Gui Ding assay method, adopt the content of high effective liquid chromatography for measuring ceftazidime, according to the content of column chromatography mensuration ceftazidime polymer, following indication content is all according to " the described dry product of pressing of Chinese pharmacopoeia (2000 editions) calculates.
Below be the specific embodiment of the present invention, described embodiment is in order to further describe the present invention, rather than restriction the present invention.
Embodiment 1
Prescription:
Ceftazidime 1000g
Arginine 50g
L-cysteine 0.1g
??????????????????????????????????
Make 1000
Preparation method:
1) supplementary material is removed outer package after, dedusting cleaning, the wiping sterilization, it is standby to enter sterilizing room;
2), with ceftazidime, arginine and L-cysteine pulverize separately, sieve, standby at clean area;
3) take by weighing step 2 at clean area) resulting ceftazidime, arginine and L-cysteine, in the ratio mixing of prescription, survey content and be sub-packed in the glass tube vial after qualified, tamponade, to roll lid, lamp inspection, be up to the standards, labeling, packing are promptly.
Embodiment 2
Prescription:
Ceftazidime 1000g
Arginine 500g
Vitamin C 1g
??????????????????????????????????
Make 1000
Preparation method:
1) supplementary material is removed outer package after, dedusting cleaning, the wiping sterilization, it is standby to enter sterilizing room;
2), with ceftazidime, arginine and vitamin C pulverize separately, sieve, standby at clean area;
3) take by weighing step 2 at clean area) resulting ceftazidime, arginine and vitamin C, in the ratio mixing of prescription, survey content and be sub-packed in the glass tube vial after qualified, tamponade, to roll lid, lamp inspection, be up to the standards, labeling, packing are promptly.
Embodiment 3
Prescription:
Ceftazidime 1000g
Arginine 100g
Sodium sulfite 0.1g
??????????????????????????????????
Make 1000
Preparation method:
1) supplementary material is removed outer package after, dedusting cleaning, the wiping sterilization, it is standby to enter sterilizing room;
2), with ceftazidime, arginine and sodium sulfite pulverize separately, sieve, standby at clean area;
3) take by weighing step 2 at clean area) resulting ceftazidime, arginine and sodium sulfite, in the ratio mixing of prescription, survey content and be sub-packed in the glass tube vial after qualified, tamponade, to roll lid, lamp inspection, be up to the standards, labeling, packing are promptly.
Embodiment 4
Prescription:
Ceftazidime 1000g
Arginine 100g
Sodium sulfite 0.5g
??????????????????????????????????
Make 1000
Preparation method:
1) purification of ceftazidime pentahydrate
Ceftazidime pentahydrate is 90.1wt.% by the content of high effective liquid chromatography for measuring ceftazidime, is 8.6wt.% by the content of measuring polymer according to column chromatography.
Ceftazidime pentahydrate 20.0g is suspended in the 100ml water, is cooled to 2 ℃ with ice-water bath, it is molten clear to material to drip the 37wt.% concentrated hydrochloric acid while stirring, obtains the ceftazidime aqueous solution.Under stirring condition, in the ceftazidime aqueous solution, drip the NaOH solution of 2N, transfer pH to 2.5, separate out the precipitation of off-white color, the elimination precipitation obtains filtrate.Then, resulting filtrate reuse ice-water bath is warming up to 8 ℃, stirs the NaOH solution that drips 2N down, and making pH is 4.0, and the ceftazidime pentahydrate crystal is separated out, and the reuse ice-water bath stirred growing the grain 7 hours with thermoregulation to 2 ℃.Sucking filtration then earlier with 30ml water, use the 50ml washing with acetone then, is drained, and vacuum drying must ceftazidime pentahydrate 16.0g.The content of ceftazidime is 98.6wt.%, and the content of polymer is 0.07wt.%.2) preparation of ceftazidime medicinal composition for injection
A) arginine and sodium sulfite are removed outer package after, the dedusting cleaning, the wiping sterilization, it is standby to enter sterilizing room;
B) at clean area, will pulverize 80 mesh sieves through the ceftazidime of above-mentioned purification process, arginine and sodium sulfite pulverize separately, mistake 60 mesh sieves, standby; Wherein the temperature of clean area is controlled at 18 ℃, and relative humidity is controlled at 45%;
C) take by weighing step 2 at clean area) resulting ceftazidime, arginine and sodium sulfite, in the ratio mixing of above-mentioned prescription, survey content and be sub-packed in 1000 bottles of glass tube vials after qualified, tamponade, to roll lid, lamp inspection, be up to the standards, labeling, packing are promptly.
Embodiment 5
Prescription:
Ceftazidime 1000g
Arginine 100g
L-cysteine 0.8g
?????????????????????????????????
Make 1000
Preparation method:
1) purification of ceftazidime pentahydrate
Ceftazidime pentahydrate is 90.2wt.% by the content of high effective liquid chromatography for measuring ceftazidime, is 8.7wt.% by the content of measuring polymer according to column chromatography.
Ceftazidime pentahydrate 20.0g is suspended in the 100ml water, is cooled to 2 ℃ with ice-water bath, it is molten clear to material to drip the 37wt.% concentrated hydrochloric acid while stirring, obtains the ceftazidime aqueous solution.Under stirring condition, in the ceftazidime aqueous solution, drip the NaOH solution of 2N, transfer pH to 1.5, separate out the precipitation of off-white color, the elimination precipitation obtains filtrate.Then, resulting filtrate reuse ice-water bath is warming up to 8 ℃, stirs the NaOH solution that drips 2N down, and making pH is 4.8, and the ceftazidime pentahydrate crystal is separated out, and the reuse ice-water bath stirred growing the grain 8 hours with thermoregulation to 5 ℃.Sucking filtration then earlier with 30ml water, use the 50ml washing with acetone then, is drained, and vacuum drying must ceftazidime pentahydrate 16.0g.The content of ceftazidime is 98.7wt.%, and the content of polymer is 0.08wt.%.2) preparation of ceftazidime medicinal composition for injection
A) arginine and sodium sulfite are removed outer package after, the dedusting cleaning, the wiping sterilization, it is standby to enter sterilizing room;
B) at clean area, will pulverize 80 mesh sieves through the ceftazidime of above-mentioned purification process, arginine and L-cysteine pulverize separately, mistake 60 mesh sieves, standby; Wherein the temperature of clean area is controlled at 26 ℃, and relative humidity is controlled at 65%;
C) take by weighing step 2 at clean area) resulting ceftazidime, arginine and L-cysteine, in the ratio mixing of above-mentioned prescription, survey content and be sub-packed in 1000 bottles of glass tube vials after qualified, tamponade, to roll lid, lamp inspection, be up to the standards, labeling, packing are promptly.
Embodiment 6
Prescription:
Ceftazidime 1000g
Arginine 100g
Sodium sulfite 0.6g
???????????????????????????????
Make 1000
Preparation method:
1) supplementary material is removed outer package after, dedusting cleaning, the wiping sterilization, it is standby to enter sterilizing room;
2),, standby with ceftazidime, arginine and sodium sulfite pulverize separately, mistake 80 mesh sieves at clean area;
3) take by weighing step 2 at clean area) resulting ceftazidime, arginine and sodium sulfite, the ratio mixing in prescription obtains ceftazidime medicinal composition; Content by the high effective liquid chromatography for measuring ceftazidime is 97.1wt.%, is 0.25wt.% by the content of measuring polymer according to column chromatography.
4) ceftazidime medicinal composition is added obtain the ceftazidime aqueous solution in the entry, then under 8-12 ℃ temperature, the pH that regulates the ceftazidime aqueous solution with hydrochloric acid is 4.6, separate out crystal, and the adding by control acid in crystallization process, make pH remain on 4.6, the ceftazidime pentahydrate crystal is separated out gradually, and the reuse ice-water bath ℃ left standstill growing the grain 5 hours with thermoregulation to 5, then sucking filtration, elder generation's water, use washing with acetone then, drain, vacuum drying is sub-packed in 1000 bottles of glass tube vials after survey content is qualified, tamponade, roll lid, lamp inspection, be up to the standards labeling, packing promptly gets ceftazidime medicinal composition for injection.The content of ceftazidime is 99.2wt.%, and the content of polymer is 0.08wt.%.
Embodiment 7
Prescription:
Ceftazidime 1000g
Arginine 500g
Vitamin C 1g
????????????????????????????
Make 1000
Preparation method:
1) supplementary material is removed outer package after, dedusting cleaning, the wiping sterilization, it is standby to enter sterilizing room;
2), with ceftazidime, arginine and vitamin C pulverize separately, sieve, standby at clean area;
3) take by weighing step 2 at clean area) resulting ceftazidime, arginine and vitamin C, the ratio mixing in prescription obtains ceftazidime medicinal composition.Content by the high effective liquid chromatography for measuring ceftazidime is 97.1wt.%, is 0.26wt.% by the content of measuring polymer according to column chromatography.
4) ceftazidime medicinal composition is added obtain the ceftazidime aqueous solution in the entry, then under 8 ℃ temperature, the pH that regulates the ceftazidime aqueous solution with hydrochloric acid is 4.2, separate out crystal, and the adding by control acid in crystallization process, make pH remain on 4.2, the ceftazidime pentahydrate crystal is separated out gradually, and the reuse ice-water bath ℃ left standstill growing the grain 5 hours with thermoregulation to 5, then sucking filtration, elder generation's water, use washing with acetone then, drain, vacuum drying is sub-packed in 1000 bottles of glass tube vials after survey content is qualified, tamponade, roll lid, lamp inspection, be up to the standards labeling, packing promptly gets ceftazidime medicinal composition for injection.The content of ceftazidime is 99.3wt.%, and the content of polymer is 0.07wt.%.
Embodiment 8
Prescription:
Ceftazidime 1000g
Arginine 100g
Sodium sulfite 0.6g
?????????????????????????????
Make 1000
Preparation method:
1) purification of ceftazidime pentahydrate
Ceftazidime pentahydrate is 90.2wt.% by the content of high effective liquid chromatography for measuring ceftazidime, is 8.7wt.% by the content of measuring polymer according to column chromatography.
Ceftazidime pentahydrate 20.0g is suspended in the 100ml water, is cooled to 2 ℃ with ice-water bath, it is molten clear to material to drip the 37wt.% concentrated hydrochloric acid while stirring, obtains the ceftazidime aqueous solution.Under stirring condition, in the ceftazidime aqueous solution, drip the NaOH solution of 2N, transfer pH to 1.5, separate out the precipitation of off-white color, the elimination precipitation obtains filtrate.Then, resulting filtrate reuse ice-water bath is warming up to 8 ℃, stirs the NaOH solution that drips 2N down, and making pH is 4.8, and the ceftazidime pentahydrate crystal is separated out, and the reuse ice-water bath stirred growing the grain 8 hours with thermoregulation to 5 ℃.Sucking filtration then earlier with 30ml water, use the 50ml washing with acetone then, is drained, and vacuum drying must ceftazidime pentahydrate 16.0g.The content of ceftazidime is 98.7wt.%, and the content of polymer is 0.08wt.%.2) preparation of ceftazidime medicinal composition for injection
A) arginine and sodium sulfite are removed outer package after, the dedusting cleaning, the wiping sterilization, it is standby to enter sterilizing room;
B) at clean area, will pulverize 80 mesh sieves through the ceftazidime of above-mentioned purification process, arginine and L-cysteine pulverize separately, mistake 60 mesh sieves, standby; Wherein the temperature of clean area is controlled at 26 ℃, and relative humidity is controlled at 65%;
C) take by weighing step 2 at clean area) resulting ceftazidime, arginine and L-cysteine, the ratio mixing in above-mentioned prescription obtains ceftazidime medicinal composition.Content by the high effective liquid chromatography for measuring ceftazidime is 97.1wt.%, is 0.26wt.% by the content of measuring polymer according to column chromatography.
4) ceftazidime medicinal composition is added obtain the ceftazidime aqueous solution in the entry, then under 8 ℃ temperature, the pH that regulates the ceftazidime aqueous solution with hydrochloric acid is 4.2, separate out crystal, and the adding by control acid in crystallization process, make pH remain on 4.2, the ceftazidime pentahydrate crystal is separated out gradually, and the reuse ice-water bath ℃ left standstill growing the grain 5 hours with thermoregulation to 5, then sucking filtration, elder generation's water, use washing with acetone then, drain, vacuum drying is sub-packed in 1000 bottles of glass tube vials after survey content is qualified, tamponade, roll lid, lamp inspection, be up to the standards labeling, packing promptly gets ceftazidime medicinal composition for injection.The content of ceftazidime is 99.9wt.%, and the content of polymer is 0.01wt.%.
Test example 1
This test example is to investigate the influence of antioxidant to the content of the content of ceftazidime in the ceftazidime medicinal composition for injection and polymer.
Method: according to " Chinese pharmacopoeia (2000 editions, the 171st page to 172 pages, Chemical Industry Press) Gui Ding assay method, adopt the content of high effective liquid chromatography for measuring ceftazidime, according to the content of column chromatography mensuration ceftazidime polymer, following indication content is all according to " the described dry product of pressing of Chinese pharmacopoeia (2000 editions) calculates.The results are shown in Table 1:
Table 1
| The content of ceftazidime | The content of polymer | |
| Reference substance | ??97.6 | ??0.26 |
| Embodiment 1 | ??99.8 | ??0.03 |
| Embodiment 2 | ??99.7 | ??0.02 |
| The content of ceftazidime | The content of polymer | |
| Embodiment 3 | ??99.5 | ??0.04 |
In the above table, reference substance is that the commercially available ceftazidime that does not contain antioxidant contains arginine formulations, embodiment 1, embodiment 2 and embodiment 3 are respectively the product of the embodiment of the invention 1, embodiment 2 and embodiment 3, as can be seen from the above table, ceftazidime content and the polymer content that contains the ceftazidime for inj preparation of antioxidant of the present invention obviously is better than reference substance.As seen, the adding of antioxidant is that certain influence is arranged to ceftazidime content and polymer content, especially can obviously reduce the content of polymer, thereby improves drug safety.
Test example 2
This test example is the stability test of ceftazidime medicinal composition for injection of the present invention.
Test method: (lot number: 081216,081217 and 081218) sample to be placed temperature be (40 ± 2) ℃, humidity for carrying out 6 months accelerated test under the condition of (75 ± 5) % to prepare three batch samples according to the method for embodiment 6.The 0th, 1, sampling at 2,3,6 the end of month, with reference to " the Chinese pharmacopoeia regulation, the content of sample survey, pyridine, polymer, pH, solution colour, clarity of solution are investigated ceftazidime medicinal composition for injection steadiness of the present invention, the results are shown in Table 1:
Table 1, accelerated test result
As can be seen from the above table, stablizing of ceftazidime medicinal composition for injection of the present invention is good, and significant the variation all taken place for its content, pyridine, polymer, pH, solution colour, clarity of solution.
Product to other embodiment of the present invention has also carried out identical test, and the result of its acquisition is similar.
Claims (10)
1. a ceftazidime medicinal composition for injection is characterized in that, described ceftazidime medicinal composition for injection is made up of following component:
Ceftazidime 1 weight portion
Arginine 0.05-0.5 weight portion
Antioxidant 0.0001-0.001 weight portion.
2. ceftazidime medicinal composition for injection according to claim 1 is characterized in that, described ceftazidime medicinal composition for injection is made up of following component:
1 part of ceftazidime
0.1 part of arginine
Antioxidant 0.0001-0.005 weight portion.
3. ceftazidime medicinal composition for injection according to claim 1 and 2 is characterized in that, described antioxidant is a kind of or its mixture in L-cysteine, sodium sulfite or the vitamin C.
4. the preparation method of any described ceftazidime medicinal composition for injection of claim 1-3 is characterized in that, described preparation method comprises the steps:
1) supplementary material is removed outer package after, dedusting cleaning, the wiping sterilization, it is standby to enter sterilizing room;
2), with ceftazidime, arginine and antioxidant pulverize separately, sieve, standby at clean area;
3) take by weighing step 2 at clean area) resulting ceftazidime, arginine and antioxidant, in the ratio mixing of prescription, survey content and be sub-packed in the glass tube vial after qualified, tamponade, to roll lid, lamp inspection, be up to the standards, labeling, packing are promptly.
5. the preparation method of ceftazidime medicinal composition for injection according to claim 4 is characterized in that step 2) described in sieve and be to cross 60-100 sieve, preferred 80 mesh sieves.
6. the preparation method of 4 described ceftazidime medicinal composition for injection as requested is characterized in that step 2) described in the temperature of clean area be controlled at 18-26 ℃, relative humidity is controlled at 45%-65%.
7. the preparation method of ceftazidime medicinal composition for injection according to claim 5, it is characterized in that described purification process is carried out purification process or/and after obtaining ceftazidime medicinal composition for injection it is carried out purification process to ceftazidime before being included in and pulverizing.
8. the preparation method of ceftazidime medicinal composition for injection according to claim 7, it is characterized in that, before pulverizing ceftazidime being carried out purification process is: ceftazidime is added in the entry, randomly add acid and make its dissolving, obtain the ceftazidime aqueous solution; PH with alkali or acid adjusting ceftazidime aqueous solution is 1.5-2.5 then, has precipitation to separate out; Remove by filter precipitation, it is 3.5-4.8 that resulting filtrate continues to regulate pH with alkali, and the control temperature is at 0-40 ℃, and the ceftazidime pentahydrate crystal structure is separated out.
9. the preparation method of ceftazidime medicinal composition for injection according to claim 8 is characterized in that, is removing by filter post precipitation, and it is 4.0-4.6 that resulting filtrate is regulated pH with alkali.
10. the preparation method of ceftazidime medicinal composition for injection according to claim 7, it is characterized in that, obtain it being carried out purification process behind the ceftazidime medicinal composition for injection be: ceftazidime added obtain the ceftazidime aqueous solution in the entry, then under 8-12 ℃ temperature, the pH that regulates the ceftazidime aqueous solution with acid is 4.2-4.6, separate out crystal, and in crystallization process, pass through the adding of control acid, make pH remain on 4.2-4.6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102239196A CN101810623B (en) | 2009-11-19 | 2009-11-19 | Ceftazidime medicinal composition for injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102239196A CN101810623B (en) | 2009-11-19 | 2009-11-19 | Ceftazidime medicinal composition for injection and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101810623A true CN101810623A (en) | 2010-08-25 |
| CN101810623B CN101810623B (en) | 2011-06-08 |
Family
ID=42618084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009102239196A Expired - Fee Related CN101810623B (en) | 2009-11-19 | 2009-11-19 | Ceftazidime medicinal composition for injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101810623B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103027894A (en) * | 2012-11-05 | 2013-04-10 | 海南卫康制药(潜山)有限公司 | Ceftazidime composition for injection and preparation method for ceftazidime composition |
| CN104860964A (en) * | 2015-04-27 | 2015-08-26 | 四川制药制剂有限公司 | Product zero load avoiding injection ceftazidime preparation method |
| CN104876949A (en) * | 2015-05-28 | 2015-09-02 | 浙江长典医药有限公司 | Ceftazidime compound entity and preparation thereof for children |
| CN105560194A (en) * | 2014-10-17 | 2016-05-11 | 广州艾奇西医药科技有限公司 | High-purity ceftazidime powder injection and preparation method thereof |
| CN106317080A (en) * | 2016-08-17 | 2017-01-11 | 陕西顿斯制药有限公司 | Ceftazidime compound prepared by adopting coupling crystallization technology and preparation thereof |
| CN110396104A (en) * | 2018-07-26 | 2019-11-01 | 赛法洛抗生素有限公司 | The new indication of Tai Siting cefotaxime pharmaceutical preparation treatment gynecological infection |
| CN110893173A (en) * | 2019-09-25 | 2020-03-20 | 上海欣峰制药有限公司 | Ceftazidime powder injection for injection and preparation method thereof |
| CN113101274A (en) * | 2021-03-31 | 2021-07-13 | 海南海灵化学制药有限公司 | Ceftazidime powder injection and preparation process thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
2009
- 2009-11-19 CN CN2009102239196A patent/CN101810623B/en not_active Expired - Fee Related
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103027894A (en) * | 2012-11-05 | 2013-04-10 | 海南卫康制药(潜山)有限公司 | Ceftazidime composition for injection and preparation method for ceftazidime composition |
| CN105560194A (en) * | 2014-10-17 | 2016-05-11 | 广州艾奇西医药科技有限公司 | High-purity ceftazidime powder injection and preparation method thereof |
| CN105560194B (en) * | 2014-10-17 | 2018-09-04 | 林立东 | Cefotaxime powder-injection of high-purity and preparation method thereof |
| CN104860964A (en) * | 2015-04-27 | 2015-08-26 | 四川制药制剂有限公司 | Product zero load avoiding injection ceftazidime preparation method |
| CN104876949A (en) * | 2015-05-28 | 2015-09-02 | 浙江长典医药有限公司 | Ceftazidime compound entity and preparation thereof for children |
| CN106317080A (en) * | 2016-08-17 | 2017-01-11 | 陕西顿斯制药有限公司 | Ceftazidime compound prepared by adopting coupling crystallization technology and preparation thereof |
| CN110396104A (en) * | 2018-07-26 | 2019-11-01 | 赛法洛抗生素有限公司 | The new indication of Tai Siting cefotaxime pharmaceutical preparation treatment gynecological infection |
| CN110893173A (en) * | 2019-09-25 | 2020-03-20 | 上海欣峰制药有限公司 | Ceftazidime powder injection for injection and preparation method thereof |
| CN113101274A (en) * | 2021-03-31 | 2021-07-13 | 海南海灵化学制药有限公司 | Ceftazidime powder injection and preparation process thereof |
| CN113101274B (en) * | 2021-03-31 | 2022-09-06 | 海南海灵化学制药有限公司 | Ceftazidime powder injection for injection and preparation process thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101810623B (en) | 2011-06-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101810623B (en) | Ceftazidime medicinal composition for injection and preparation method thereof | |
| CN102451154A (en) | Netilmicin sulfate injection and preparation method thereof | |
| CN103989630B (en) | Moxifloxacin hydrochloride injection and preparation method thereof | |
| CN102626409B (en) | A kind of pharmaceutical composition containing 18 seed amino acids | |
| CN105924456B (en) | A kind of Cefminox sodium compound and its preparation for reducing adverse reaction | |
| JP2006291028A (en) | Low-molecular heparin or salt thereof, and manufacturing method thereof | |
| CN105085612B (en) | N-(the 2)-Ala-Gln compound adopting particle crystal habit optimisation technique to prepare and preparation | |
| CN105147599B (en) | Netilmicin sulfate injection and preparation method | |
| CN105213301B (en) | Netilmicin sulfate injection and its quality control method | |
| CN106236707A (en) | A kind of preparation method of carboxylic maltose ferrum | |
| US4698361A (en) | Tris-chydroxymethyl) aminomethane salt of 4-chloro-N-furfuryl-5-sulfamoyl anthranilic acid and diuretic compositions containing the same | |
| CN110393719A (en) | The new indication of cefoperazone sodium sulbactam sodium pharmaceutical preparation treatment infectious endocarditis | |
| CN102824304B (en) | Cefepime hydrochloride composition for injection and its preparation method | |
| CN110393720A (en) | Qu Suofen Ceftriaxone Sodium pharmaceutical preparation treats the new indication of immunity function immunocompromised patients infection | |
| CN104098491A (en) | Acetylcysteine compound and acetylcysteine solution being used for inhalation and containing same | |
| CN1751048A (en) | Method for preparing polymorphism of irinotecan hydrochloride | |
| EP4221723A1 (en) | Methods of preparing iron complexes | |
| CN103142617A (en) | Cefuroxime lysine medicinal composition | |
| CN110893173A (en) | Ceftazidime powder injection for injection and preparation method thereof | |
| CN115811988A (en) | Blood purification molecule concentrate and preparation method and application thereof | |
| CN107854486A (en) | The medical composition and its use of the various trace elements of injection | |
| CN103450086A (en) | Ozagrel compound, preparation method and pharmaceutical composition of ozagrel compound | |
| CN102824310A (en) | Cefotiam-hydrochloride-containing medicine preparation and preparation method thereof | |
| CN113876723A (en) | Preparation process of cefotaxime sodium for injection | |
| CN103463094B (en) | Medicine composition of cefpiramide sodium and infant compound amino acid injection (19AA-I) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: CHENG XIANFENG Free format text: FORMER OWNER: LUO CHENG Effective date: 20120511 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 364000 LONGYAN, FUJIAN PROVINCE TO: 230601 HEFEI, ANHUI PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20120511 Address after: 230601, Anhui Hefei economic and Technological Development Zone, Fairview Avenue and Qinglong Lake Road junction southwest corner Patentee after: Cheng Xianfeng Address before: Room 601, building A, Shengshi Road, Renmin Road, Fujian, Longyan, 364000 Patentee before: Luo Cheng |
|
| ASS | Succession or assignment of patent right |
Owner name: LUO CHENG Free format text: FORMER OWNER: CHENG XIANFENG Effective date: 20130329 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 230601 HEFEI, ANHUI PROVINCE TO: 350001 LONGYAN, FUJIAN PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20130329 Address after: Room 601, building A, Shengshi Road, Renmin Road, Fujian, Longyan, 350001 Patentee after: Luo Cheng Address before: 230601, Anhui Hefei economic and Technological Development Zone, Fairview Avenue and Qinglong Lake Road junction southwest corner Patentee before: Cheng Xianfeng |
|
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20100825 Assignee: HEFEI E-FAN BIOMEDICINE CO.,LTD. Assignor: Luo Cheng Contract record no.: 2013990000237 Denomination of invention: Ceftazidime medicinal composition for injection and preparation method thereof Granted publication date: 20110608 License type: Exclusive License Record date: 20130514 |
|
| LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
| ASS | Succession or assignment of patent right |
Owner name: HEFEI YIFAN BIOLOGICAL MEDICINE CO., LTD. Free format text: FORMER OWNER: LUO CHENG Effective date: 20130716 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 350001 LONGYAN, FUJIAN PROVINCE TO: 230601 HEFEI, ANHUI PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20130716 Address after: 230601, Jinxiu Road, Hefei economic and Technological Development Zone, Anhui Province Patentee after: HEFEI E-FAN BIOMEDICINE CO.,LTD. Address before: Room 601, building A, Shengshi Road, Renmin Road, Fujian, Longyan, 350001 Patentee before: Luo Cheng |
|
| EC01 | Cancellation of recordation of patent licensing contract |
Assignee: HEFEI E-FAN BIOMEDICINE CO.,LTD. Assignor: Luo Cheng Contract record no.: 2013990000237 Date of cancellation: 20130710 |
|
| LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Ceftazidime medicinal composition for injection and preparation method thereof Effective date of registration: 20161206 Granted publication date: 20110608 Pledgee: The Bank of Hangzhou Limited by Share Ltd. Hefei Baohe branch Pledgor: HEFEI E-FAN BIOMEDICINE CO.,LTD. Registration number: 2016990001069 |
|
| PLDC | Enforcement, change and cancellation of contracts on pledge of patent right or utility model | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20171106 Granted publication date: 20110608 Pledgee: The Bank of Hangzhou Limited by Share Ltd. Hefei Baohe branch Pledgor: HEFEI E-FAN BIOMEDICINE CO.,LTD. Registration number: 2016990001069 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Ceftazidime medicinal composition for injection and preparation method thereof Effective date of registration: 20180929 Granted publication date: 20110608 Pledgee: Shanghai Pudong Development Bank Limited by Share Ltd. Hefei branch Pledgor: HEFEI E-FAN BIOMEDICINE CO.,LTD. Registration number: 2018340000527 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230525 Granted publication date: 20110608 Pledgee: Shanghai Pudong Development Bank Limited by Share Ltd. Hefei branch Pledgor: HEFEI E-FAN BIOMEDICINE CO.,LTD. Registration number: 2018340000527 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110608 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |