CN106420760A - Ceftibuten pharmaceutical composition for treating surgical infection - Google Patents
Ceftibuten pharmaceutical composition for treating surgical infection Download PDFInfo
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- CN106420760A CN106420760A CN201610837273.0A CN201610837273A CN106420760A CN 106420760 A CN106420760 A CN 106420760A CN 201610837273 A CN201610837273 A CN 201610837273A CN 106420760 A CN106420760 A CN 106420760A
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- Prior art keywords
- ceftibuten
- pharmaceutical composition
- arginine
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- 229960004086 ceftibuten Drugs 0.000 title claims abstract description 100
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 22
- UNJFKXSSGBWRBZ-BJCIPQKHSA-N ceftibuten Chemical compound S1C(N)=NC(C(=C\CC(O)=O)\C(=O)N[C@@H]2C(N3C(=CCS[C@@H]32)C(O)=O)=O)=C1 UNJFKXSSGBWRBZ-BJCIPQKHSA-N 0.000 title claims abstract 11
- 208000015181 infectious disease Diseases 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 33
- 239000003814 drug Substances 0.000 claims abstract description 32
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 16
- 239000004475 Arginine Substances 0.000 claims abstract description 13
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims description 30
- 239000013078 crystal Substances 0.000 claims description 16
- 206010067268 Post procedural infection Diseases 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
- 229940079593 drug Drugs 0.000 abstract description 20
- 239000012535 impurity Substances 0.000 abstract description 17
- 238000000034 method Methods 0.000 abstract description 14
- 239000000203 mixture Substances 0.000 abstract description 13
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 206010067484 Adverse reaction Diseases 0.000 abstract description 4
- 230000006838 adverse reaction Effects 0.000 abstract description 4
- 238000004806 packaging method and process Methods 0.000 abstract description 3
- 238000011068 loading method Methods 0.000 abstract description 2
- 238000001228 spectrum Methods 0.000 abstract description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 abstract 1
- SSWTVBYDDFPFAF-DKOGRLLHSA-N ceftibuten dihydrate Chemical compound O.O.S1C(N)=NC(C(=C\CC(O)=O)\C(=O)N[C@@H]2C(N3C(=CCS[C@@H]32)C(O)=O)=O)=C1 SSWTVBYDDFPFAF-DKOGRLLHSA-N 0.000 description 90
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 238000012360 testing method Methods 0.000 description 16
- 229920000642 polymer Polymers 0.000 description 15
- 239000002775 capsule Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 150000001336 alkenes Chemical class 0.000 description 9
- 238000004090 dissolution Methods 0.000 description 9
- 239000004744 fabric Substances 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 239000012046 mixed solvent Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 7
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 208000003455 anaphylaxis Diseases 0.000 description 5
- BQFCCCIRTOLPEF-UHFFFAOYSA-N chembl1976978 Chemical compound CC1=CC=CC=C1N=NC1=C(O)C=CC2=CC=CC=C12 BQFCCCIRTOLPEF-UHFFFAOYSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 206010002198 Anaphylactic reaction Diseases 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 230000036783 anaphylactic response Effects 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 229930186147 Cephalosporin Natural products 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
- 229940124587 cephalosporin Drugs 0.000 description 3
- 150000001780 cephalosporins Chemical class 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 239000013558 reference substance Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- YKMDNKRCCODWMG-UHFFFAOYSA-M 2,5-dinitrobenzoate Chemical compound [O-]C(=O)C1=CC([N+]([O-])=O)=CC=C1[N+]([O-])=O YKMDNKRCCODWMG-UHFFFAOYSA-M 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 206010057190 Respiratory tract infections Diseases 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229960001247 ceftibuten dihydrate Drugs 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- -1 fluidizer Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000004088 simulation Methods 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- SCNWTQPZTZMXBG-UHFFFAOYSA-N 2-methyloct-2-enoic acid Chemical compound CCCCCC=C(C)C(O)=O SCNWTQPZTZMXBG-UHFFFAOYSA-N 0.000 description 1
- 235000019890 Amylum Nutrition 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 241001478240 Coccus Species 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 206010064147 Gastrointestinal inflammation Diseases 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical group OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000007596 consolidation process Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- CKQQMPJQZXIYMJ-UHFFFAOYSA-N dihydrate;dihydrochloride Chemical compound O.O.Cl.Cl CKQQMPJQZXIYMJ-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical group 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000015689 metaplastic ossification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910052756 noble gas Inorganic materials 0.000 description 1
- 150000002835 noble gases Chemical class 0.000 description 1
- 229940124588 oral cephalosporin Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000001374 post-anti-biotic effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 238000005829 trimerization reaction Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/12—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/22—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with radicals containing only hydrogen and carbon atoms, attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
Abstract
The invention belongs to the technical field of medicines, and discloses a ceftibuten pharmaceutical composition for treating surgical infection. The composition consists of ceftibuten and arginine; the structure of a ceftibuten crystalline compound is shown as formula (I) (as shown in Description); the crystalline compound is determined by virtue of a powder X-ray diffraction method; and an X-ray powder diffraction spectrum, which is represented by a diffraction angle ranging from 2[theta]-0.2 degrees to 2[theta]+0.2 degrees, is shown as Drawing 1. The pharmaceutical composition provided by the invention is high in purity, low in impurity content and good in clarity, and moreover, the pharmaceutical composition can guarantee a sub-packaging efficiency in production, reduce differences in a loading quantity, greatly reduce an occurrence rate of adverse reactions and enhance a stability.
Description
Technical field
The invention belongs to pharmaceutical technology field is and in particular to a kind of medicine ceftibuten treating Postoperative infection combines
Thing.
Background technology
Ceftibuten (Ceftibuten) is broad-spectrum cephalosporin to be administered orally by the third generation that Yan Yeyi company of Japan is developed, right
Most of gram negative bacilli and some positive coccus have stronger antibacterial action, to plasmid-mediated beta-lactamase height
Stable, and there is post antibiotic effect;There is has a broad antifungal spectrum, the features such as antibacterial activity is strong, bioavailability is high, for treatment by
The various infection that sensitive strain causes, including upper respiratory tract infection, lower respiratory infection, the urinary system that oozes infection, enteritis and gastrointestinal
Inflammation etc..
The chemical name of ceftibuten be (+)-(6R, 7R) -7 β-[(Z) -2- (2- amino -4- thiazole) -4- carboxyl -2-
(Z)-crotonamide] -8- oxygen -5- sulfur -1- nitrogen bicyclic [4.2.0] oct-2-ene -2- carboxylic acid two water thing, structural formula such as formula I institute
Show:
Formula().
Beta-Lactam antibiotic, such as penicillin medicine and Cephalosporins, due to the less stable of parent nucleus, hold
Easily reset, decompose and polyreaction, the polymer product being formed and anaphylactic shock have close relationship.In penicillin
Averagely in 21.44 μ g/g, anaphylaxiss incidence rate is 0.2% to polymeric impurities;Polymeric impurities are averagely in 51.24 μ g/g
When, anaphylaxiss incidence rate is 0.43%;During polymeric impurities average out to 76.7 μ g/g, allergy rate is 0.74%.Cephalosporin
Though anaphylaxiss are so serious not as good as penicillin, when polymer is high, human allergy equally can be caused to react.
Ceftibuten chance light, heat, water, oxidation etc. are unstable, are also easy to produce catabolite, particularly suffer from the situation of high temperature
Under, tending to occur degraded and polyreaction, generating ceftibuten dimer, trimer and polymer etc. polymer, thus leading
Active constituents of medicine content is caused to reduce, color and luster is strengthened, polymeric impurities content raises.In addition, expired ceftibuten antibiotic,
Because the resting period is long, so that active constituents of medicine content is reduced, darken, polymer content raises.Further, exist
In some cases, because controlling of production process is improper, obtained ceftibuten dihydrate, ceftibuten dimer, trimerization
Thing and polymer etc. polymer content is especially high.And polymer content high when, easily make human body produce anaphylaxiss.So for
The high ceftibuten dihydrate of this kind of polymeric impurities content or ceftibuten pharmaceutical preparation are it is necessary to carry out pure further
Change, ceftibuten dihydrochloride dihydrate crystal that obtain high-quality, that purity is high.
Additionally, the poorly water-soluble of ceftibuten, mobility are bad, there is hygroscopicity etc. to preparation preparation bring tired
Difficulty, the capsule of its preparation mostly has that dissolution is low, and stability is bad, the defect such as polymer content height.
US4812561 discloses a kind of crystal hydrate of oral cephalosporin and combinations thereof, its disclosed crystallization
Hydrate is dihydrate, trihydrate or its mixture, and the preparation method of this crystalline hydrate is:By material dissolution in sour water
In solution, the pH making solution is in about room temperature(Specifically at 0-70 DEG C)Rise(Specifically rise to pH1.5-5.0)To separate crystallization.Must
When wanting, stirring mixture makes crystallization complete.Isolate wet crystallization, under room temperature and about atmospheric pressure, be not less than in relative humidity
It is dried in 15% noble gases.The crystalline hydrate that the method is obtained has the stability of height, and accelerated test confirms,
After one month, it remains to keep 97.8% efficiency.Present invention also offers a kind of compositionss of energy stable for extended periods of time, find
Sealing by this hydrate loading snap fit capsule and with gelatin band can make its pole not easy to change and inactivate.The preparation of capsule of the present invention
Specific as follows:By the hydrate of pharmacologically effective dose and additive(As filler, lubricant)Mutually mix, be then charged into capsule,
The periphery of capsule lid and the whole junction of body coats aqueous gelatin solution, is dried and forms gelatin band.Snap fit capsule can be common
Commodity capsule, does not have the restriction of special size and color, can contain fuel and/or pigment.But, applicant is through substantial amounts of
Experimental study confirms, the impurity content of the crystalline hydrate of gained of the present invention, especially polymer content are still very high, its flowing
Property, dissolubility also need to be improved.Although prepared capsule purity and stability are preferably, its dissolution, polymeric impurities
Content is unsatisfactory.
Preparation method the method that CN105153198A discloses a kind of ceftibuten is a kind of new to prepare ceftibuten
Method, its high income, purity is high, easy and simple to handle, is the production technology of a green cleaning, is suitable for the industry of certain scale
Metaplasia is produced.HPLC purity 98.5%-99.2%, its diffraction numerical value is close with US4812561 after measured, gained crystalline hydrate miscellaneous
Matter content, especially polymer content are high, and its mobility, dissolubility are also poor.
CN104546862A discloses a kind of ceftibuten pharmaceutical composition and preparation method thereof, and wherein capsule is by cephalo
Cloth alkene, amylum pregelatinisatum, Microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, micropowder silica gel and Pulvis Talci are prepared through specific
Method is made.The capsule that applicant prepares to it has carried out dissolution, defects inspecting and stability test, finds its dissolution
Difference, impurity content is high, and stability is also very poor.
EP3031450A1 discloses a kind of ceftibuten capsule, it comprises binding agent, disintegrating agent, lubricant, fluidizer
Agent, prescription disclosed in embodiment is two water ceftibutens, magnesium stearate, Microcrystalline Cellulose, silica sol, hydroxyacetic acid form sediment
Powder sodium, by controlling the particle diameter of two water ceftibutens, solves the dissolution leading to preparation due to ceftibuten low aqueous solubility not
Good, a difficult problem for impact drug absorption, ceftibuten preparation newly developed is easy to and rapid dispersion in vivo, have high absorption and
Bioavailability.The capsule that applicant prepares to it has carried out defects inspecting and stability test, finds that its impurity content is high, surely
Qualitative also poor, dissolution needs to be improved further.
WO2013151518A1 discloses and a kind of comprises at least two different compositionss with high water solubility pH agent
Ceftibuten capsule preparations, described preparation comprises except at least one pharmaceutically acceptable excipient and tablet composition.Can
Disintegrating agent, fluidizer, lubricant and bonding can be comprised with excipient pharmaceutically acceptable used in the preparation of the present invention
Agent, the capsule dissolution that it is obtained is higher, but finds that its impurity, polymer content are higher through test, and less stable.
The present inventor, with existing ceftibuten crude product as raw material, through lot of experiments, has been obtained one kind and has been totally different from now
There is technology(As US4812561, CN105153198A, commercially available prod etc.)Novel crystal forms ceftibuten crystalline compounds, and
By test, surprisingly find that this crystalline compounds purity is high, polymer content is low, good stability, and is difficult moisture absorption, mobility
Good, substantially increase its dissolubility.Not only purity is high, impurity content is low for the pharmaceutical composition made using this crystalline compounds,
Clarity is good, and can guarantee that subpackage efficiency in production, content uniformity are little, and adverse reaction rate substantially reduces, stability
More preferably.
Content of the invention
It is an object of the invention to provide a kind of ceftibuten pharmaceutical composition, not only purity is high, miscellaneous for this pharmaceutical composition
Matter content is low, clarity is good, and can guarantee that subpackage efficiency in production, content uniformity are little, and adverse reaction rate drops significantly
Low, stability is more preferable.
For realizing the purpose of the present invention, the present invention adopts the following technical scheme that:
A kind of medicine ceftibuten compositionss treating Postoperative infection, the consisting of of described pharmaceutical composition:Cephalo cloth
Alkene 1 weight portion, arginine 0.01-0.03 weight portion;
As shown in formula I, this compound is measured the structural formula of described ceftibuten with powder X-ray diffraction algoscopy, with 2 θ
X-ray powder diffraction pattern that ± 0.2 ° of angle of diffraction represents as shown in figure 1,
Formula().
Preferably, the consisting of of described ceftibuten pharmaceutical composition:Ceftibuten 1 weight portion, arginine 0.02 weight
Amount part.
Described ceftibuten pharmaceutical composition is prepared from by following preparation method:
(1)Weigh ceftibuten crystal and arginine in proportion, be sufficiently mixed;
(2)Subpackage to sterilize after cillin bottle in and jump a queue.
Above-mentioned ceftibuten crystal is obtained by following methods:
Take ceftibuten crude drug, in the methanol of addition uniform temperature, the mixed solvent A of dimethylformamide, obtain solution;So
Apply stationary magnetic field in the horizontal direction of the liquid level of resulting solution afterwards, and to Deca in solution under conditions of this stationary magnetic field
Acetone, ethyl acetate, the mixed solvent B of ether;After being added dropwise to complete, stand 3-5 hour, filter, filter cake washing with alcohol, vacuum
2-4 hour is dried, obtains described ceftibuten crystalline compounds.
Above-mentioned ceftibuten crude drug can be the synthesis side using the ceftibuten disclosed in the method for prior art
Ceftibuten or commercially available ceftibuten crude drug that method prepares.
In above-mentioned preparation method, wherein, described uniform temperature is 15-25 DEG C.Described mixed solvent A volume(ml)For cephalo
6-8 times of cloth alkene crude drug weight (g), methanol and dimethylformamide volume ratio are 1:2.5.Described magnetic field intensity is 0.8T-
1.5T.Described mixed solvent B volume(ml)For 8-10 times of ceftibuten crude drug weight (g), acetone, ethyl acetate and ether
Volume ratio is 2:3:5.
Compared with prior art, the invention has the advantages that:
(1)Not only purity is high for ceftibuten crystalline compounds provided by the present invention, and polymer content is low, good stability, and
It is difficult moisture absorption, and mobility, dissolubility etc. are substantially better than prior art;
(2)The preparation method process is simple of ceftibuten provided by the present invention, high income, repeatability is strong, is suitable for industrialization
Produce;
(3)Not only purity is high for pharmaceutical composition containing this ceftibuten crystalline compounds provided by the present invention, impurity content
Low, clarity is good, and can guarantee that subpackage efficiency in production, content uniformity are little, and adverse reaction rate substantially reduces, stable
Property is more preferable.
Brief description
Fig. 1 is that the x-ray powder of the ceftibuten crystalline compounds containing in ceftibuten pharmaceutical composition of the present invention spreads out
Penetrate figure.
Fig. 2 is the heat analysis collection of illustrative plates of the ceftibuten crystalline compounds shown in Fig. 1.
Specific embodiment
With embodiment, technical scheme is described in detail below, it will help the technical side to the present invention
The advantage of case, effect have and further understand, embodiment does not limit protection scope of the present invention, protection scope of the present invention by
Claim is determining.
The preparation of embodiment 1 ceftibuten crystalline compounds
Take ceftibuten crude drug, the volume adding 15 DEG C is the methanol of 6 times of ceftibuten weight, the mixing of dimethylformamide
In solvent orange 2 A, methanol and dimethylformamide volume ratio are 1:2.5, obtain solution;Then in the level side of the liquid level of resulting solution
Upwards apply magnetic field intensity be 0.8T stationary magnetic field, and under conditions of this stationary magnetic field to Deca volume in solution be cephalo
8 times of acetone of cloth alkene weight, ethyl acetate, the mixed solvent of ether, the volume ratio of acetone, ethyl acetate and ether is 2:3:5;Drip
Plus after the completion of, stand 3-5 hour, filter, filter cake washing with alcohol, be vacuum dried 2-4 hour, obtain described ceftibuten brilliant
Body compound.
Measured with powder X-ray diffraction algoscopy(The same US4812561 of assay method), represented with the 2 θ ± 0.2 ° angles of diffraction
X-ray powder diffraction collection(Fig. 1)5.0 °, 7.2 °, 10.0 °, 12.1 °, 14.7 °, 18.2 °, 21.5 °, 22.3 °, 23.6 °,
25.0 °, 27.1 °, 28.4 °, 28.7 °, 30.5 °, show characteristic diffraction peak at 31.2 °.
Measuring moisture using Ka Shi aquametry is 8.08wt%, substantially identical with theoretical value.
Measured using thermogravimetric analysiss, result is as shown in Fig. 2 crystal water content is 8.07wt%, substantially identical with theoretical value.
The preparation of embodiment 2 ceftibuten crystalline compounds
Take ceftibuten crude drug, the volume adding 20 DEG C is the methanol of 7 times of ceftibuten weight, the mixing of dimethylformamide
In solvent orange 2 A, methanol and dimethylformamide volume ratio are 1:2.5, obtain solution;Then in the level side of the liquid level of resulting solution
Upwards apply magnetic field intensity be 1.2T stationary magnetic field, and under conditions of this stationary magnetic field to Deca volume in solution be cephalo
9 times of acetone of cloth alkene weight, ethyl acetate, the mixed solvent of ether, the volume ratio of acetone, ethyl acetate and ether is 2:3:5;Drip
Plus after the completion of, stand 3-5 hour, filter, filter cake washing with alcohol, be vacuum dried 2-4 hour, obtain described ceftibuten brilliant
Body compound.
Measured with powder X-ray diffraction algoscopy, same with the X-ray powder diffraction collection that the 2 θ ± 0.2 ° angles of diffraction represent
Embodiment 1.
The preparation of embodiment 3 ceftibuten crystalline compounds
Take ceftibuten crude drug, the volume adding 25 DEG C is the methanol of 8 times of ceftibuten weight, the mixing of dimethylformamide
In solvent orange 2 A, methanol and dimethylformamide volume ratio are 1:2.5, obtain solution;Then in the level side of the liquid level of resulting solution
Upwards apply magnetic field intensity be 1.5T stationary magnetic field, and under conditions of this stationary magnetic field to Deca volume in solution be cephalo
10 times of acetone of cloth alkene weight, ethyl acetate, the mixed solvent of ether, the volume ratio of acetone, ethyl acetate and ether is 2:3:5;
After being added dropwise to complete, stand 3-5 hour, filter, filter cake washing with alcohol, be vacuum dried 2-4 hour, obtain described ceftibuten
Crystalline compounds.
Measured with powder X-ray diffraction algoscopy, same with the X-ray powder diffraction collection that the 2 θ ± 0.2 ° angles of diffraction represent
Embodiment 1.
The preparation of embodiment 4 ceftibuten crystalline compounds
Take ceftibuten crude drug, the volume adding 15 DEG C is the methanol of 7 times of ceftibuten weight, the mixing of dimethylformamide
In solvent orange 2 A, methanol and dimethylformamide volume ratio are 1:2.5, obtain solution;Then in the level side of the liquid level of resulting solution
Upwards apply magnetic field intensity be, the stationary magnetic field of 1.2T, and under conditions of this stationary magnetic field to Deca volume in solution be head
Spore 10 times of acetone of cloth alkene weight, ethyl acetate, the mixed solvent of ether, the volume ratio of acetone, ethyl acetate and ether is 2:3:
5;After being added dropwise to complete, stand 3-5 hour, filter, filter cake washing with alcohol, be vacuum dried 2-4 hour, obtain described cephalo cloth
Alkene crystalline compounds.
Measured with powder X-ray diffraction algoscopy, same with the X-ray powder diffraction collection that the 2 θ ± 0.2 ° angles of diffraction represent
Embodiment 1.
The preparation of embodiment 5 ceftibuten crystalline compounds
Take ceftibuten crude drug, the volume adding 25 DEG C is the methanol of 6 times of ceftibuten weight, the mixing of dimethylformamide
In solvent orange 2 A, methanol and dimethylformamide volume ratio are 1:2.5, obtain solution;Then in the level side of the liquid level of resulting solution
Upwards apply magnetic field intensity be 0.8T stationary magnetic field, and under conditions of this stationary magnetic field to Deca volume in solution be cephalo
9 times of acetone of cloth alkene weight, ethyl acetate, the mixed solvent of ether, the volume ratio of acetone, ethyl acetate and ether is 2:3:5;Drip
Plus after the completion of, stand 3-5 hour, filter, filter cake washing with alcohol, be vacuum dried 2-4 hour, obtain described ceftibuten brilliant
Body compound.
Measured with powder X-ray diffraction algoscopy, same with the X-ray powder diffraction collection that the 2 θ ± 0.2 ° angles of diffraction represent
Embodiment 1.
Example of formulations 1:The preparation of ceftibuten pharmaceutical composition:
Consist of:Ceftibuten crystal 1 weight portion that the present invention provides, arginine 0.01 weight portion.
Preparation method is:
(1)Weigh ceftibuten crystal and arginine in proportion, be sufficiently mixed;
(2)Subpackage to sterilize after cillin bottle in and jump a queue.
Example of formulations 2:The preparation of ceftibuten pharmaceutical composition:
Consist of:Ceftibuten crystal 1 weight portion that the present invention provides, arginine 0.02 weight portion.
Preparation method is:
(1)Weigh ceftibuten crystal and arginine in proportion, be sufficiently mixed;
(2)Subpackage to sterilize after cillin bottle in and jump a queue.
Example of formulations 3:The preparation of ceftibuten pharmaceutical composition:
Consist of:Ceftibuten crystal 1 weight portion that the present invention provides, arginine 0.03 weight portion.
Preparation method is:
(1)Weigh ceftibuten crystal and arginine in proportion, be sufficiently mixed;
(2)Subpackage to sterilize after cillin bottle in and jump a queue.
Trial target 1:Ceftibuten crystalline compounds prepared by the embodiment of the present invention 1;
Trial target 2:Ceftibuten crystalline compounds prepared by the embodiment of the present invention 4;
Reference substance 1:Method according to CN105153198A embodiment 1 is obtained ceftibuten crystalline compounds;
Reference substance 2:Method according to US4812561 example 2 is obtained ceftibuten crystalline compounds.
Experimental example 1:Fluidity test
This experimental example evaluates the mobility of sample by the angle of repose of determination sample, and concrete grammar is as follows:Take sample particle, from
Flow in fixing little funnel in the surface plate of circle, until obtaining highest cone, measure cone height H and radius R,
Calculate α angle of repose by tan α=H/R, the results are shown in Table 1, angle of repose is bigger, mobility is poorer.
Table 1 fluidity test result
As known from Table 1, compared with ceftibuten of the prior art, what the present invention provided ceftibuten compound flow shows
Write and improve, be conducive to the preparation of preparation, dissolution, the raising of bioavailability.
Experimental example 2:Dissolubility test
Add appropriate distilled water in the low capacity bottle with constant temperature jacket, add ceftibuten at 25 DEG C to not re-dissolved
Till, start magnetic stirrer, continuously stirred under constant temperature, system is in the state of two-phase coexistent all the time in experimentation, 70
In the liquid phase of system after minute, the concentration of ceftibuten is the dissolubility at a temperature of this.It is sampled after 2 hours analyzing, take
The close meansigma methodss of adjacent two times result as measured value of experiment, before sampling, in order that solid-liquid is sufficiently separated, stop stirring after,
Not molten ceftibuten is deposited to the bottom of low capacity bottle, extracts a small amount of upper clear supernate with syringe, with 0.45 micron of filter
Filter, take sample from filtrate, measure the content of ceftibuten by HPLC(Concentration(mg/ml)).The results are shown in Table 2.
Under table 2 room temperature, ceftibuten crystal compound of the present invention and the water solublity of prior art crystal formation contrast
From table 2 it can be seen that the water solublity of the ceftibuten crystal compound of present invention offer is compared with prior art, have aobvious
Write and improve.
Experimental example 3:Wettability test
Each sample opening is put in clean culture dish, spreads out into≤thick the thin layer of 5mm, each two parts, be respectively put into constant humidity hermetic container
In, place 10 days under conditions of relative humidity 75% and 92.5% at 25 DEG C, sampled in the 5th day and the 10th day, to take
Xie Erfa measures the moisture of each sample, and result of the test was compared with 0 day, and experimental result is shown in Table 3.
Table 3 hygroscopicity test results
As can be seen from the above table, the ceftibuten crystalline compounds that the present invention provides are substantially non-hygroscopic under high humidity conditions, its
Stability under high humidity environment is substantially better than the ceftibuten using prior art.
Experimental example 4:Influence factor tests
By trial target and reference substance simulation listing packaging, in 60 DEG C of high temperature, illumination 4500Lx, high humidity(RH90%±5%)Under the conditions of
Place 10 days, detected by stability high spot reviews project, compare with 0 day sample, the results are shown in Table 4.
Table 4 compounds affect factorial experimentss result
The height of drug quality is directly connected to the health of millions upon millions of working people's bodies, is also related to the one-tenth of China's economic construction
Effect, the consolidation of national defence and nationality flourishing;It has been far from the thing of medical industry enterprise scope itself, but the whole people
Race, the major issue in the world.Those skilled in the art all clearly know, in the present age that pharmaceutical technology is flourishing, drug safety standard is not by
Disconnected lifting, the purity also more and more higher of prepared medicine, it is effectively reduced impurity content, even several percentage points of zero point,
The generation of untoward reaction can also be effectively reduced, therefore impurity content is most important to drug quality and people's drug safety.
Medicine needs to store and transport just can cure the sickness to save the patient from production to the process of circulation, therefore, medicine in storage and transportation
Quality is particularly important, and stability is the key determining drug quality quality, in medicine storage and transportation, stability
Bad, impurity change directly affects greatly people's drug safety.
As can be seen from the above table, the relevant thing of the ceftibuten crystalline compounds being obtained using the method that the present invention provides
Matter, polymer equal size are all very low, and stability is significantly better than the ceftibuten of prior art, effectively improve drug safety
Property and the stability of storage, reduce the generation of untoward reaction.
Above-mentioned experimental example 1-4 is also carried out to the ceftibuten crystalline compounds of other embodiments of the present invention, it obtains
Result is similar.
Experimental example 6:Compositionss influence factor tests
Formulation test product 1:Ceftibuten pharmaceutical composition prepared by invention formulation embodiment 1.
Formulation test product 2:Ceftibuten pharmaceutical composition prepared by invention formulation embodiment 2.
By formulation test product simulation listing packaging, in 60 DEG C of high temperature, illumination 4500Lx, high humidity(RH90%±5%)Under the conditions of
Place 10 days, detected by stability high spot reviews project, compare with 0 day sample, the results are shown in Table 5.
Table 5 preparation influence factor's result of the test
Found by result above, the pharmaceutical composition purity containing this ceftibuten crystalline compounds prepared by the present invention is high,
Impurity content is low, good stability.
Above-mentioned test is also carried out to the ceftibuten pharmaceutical composition of present invention other example of formulations, its knot obtaining
Really similar.
Claims (3)
1. a kind of medicine ceftibuten compositionss treating Postoperative infection are it is characterised in that described pharmaceutical composition
Consist of:Ceftibuten 1 weight portion, arginine 0.01-0.03 weight portion;
As shown in formula I, this compound is measured the structural formula of described ceftibuten with powder X-ray diffraction algoscopy, with 2 θ
X-ray powder diffraction pattern that ± 0.2 ° of angle of diffraction represents as shown in figure 1,
Formula().
2. the medicine ceftibuten compositionss for the treatment of Postoperative infection according to claim 1 are it is characterised in that described
The consisting of of pharmaceutical composition:Ceftibuten 1 weight portion, arginine 0.02 weight portion.
3. according to claim 1 and 2 treatment Postoperative infection medicine ceftibuten compositionss it is characterised in that
Described compositionss are prepared from by following preparation method:
(1)Weigh ceftibuten crystal and arginine in proportion, be sufficiently mixed;
(2)Subpackage to sterilize after cillin bottle in and jump a queue.
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WO2023278945A1 (en) * | 2021-07-01 | 2023-01-05 | Qpex Biopharma, Inc. | Crystalline forms of ceftibuten |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007129176A2 (en) * | 2006-04-28 | 2007-11-15 | Wockhardt Ltd | Improvements in therapy for treating resistant bacterial infections |
CN101129381A (en) * | 2006-08-25 | 2008-02-27 | 天津和美生物技术有限公司 | Antibiotic compound containing beta-lactam antibiotic and ion chelating agent |
CN103565759A (en) * | 2013-10-15 | 2014-02-12 | 海南卫康制药(潜山)有限公司 | Ceftibuten composition freeze-dried powder for injection |
-
2016
- 2016-09-21 CN CN201610837273.0A patent/CN106420760A/en not_active Withdrawn
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007129176A2 (en) * | 2006-04-28 | 2007-11-15 | Wockhardt Ltd | Improvements in therapy for treating resistant bacterial infections |
CN101129381A (en) * | 2006-08-25 | 2008-02-27 | 天津和美生物技术有限公司 | Antibiotic compound containing beta-lactam antibiotic and ion chelating agent |
CN103565759A (en) * | 2013-10-15 | 2014-02-12 | 海南卫康制药(潜山)有限公司 | Ceftibuten composition freeze-dried powder for injection |
Non-Patent Citations (1)
Title |
---|
MITSURU YOSHIOKA: "Synthetic studies related to oral β-lactam antibiotics", 《PURE & APPL. CHEM.》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023278945A1 (en) * | 2021-07-01 | 2023-01-05 | Qpex Biopharma, Inc. | Crystalline forms of ceftibuten |
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