CN102526741A - Composition of arginine and series of cephalosporin acids - Google Patents
Composition of arginine and series of cephalosporin acids Download PDFInfo
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- CN102526741A CN102526741A CN2010105805244A CN201010580524A CN102526741A CN 102526741 A CN102526741 A CN 102526741A CN 2010105805244 A CN2010105805244 A CN 2010105805244A CN 201010580524 A CN201010580524 A CN 201010580524A CN 102526741 A CN102526741 A CN 102526741A
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- 239000002253 acid Substances 0.000 title claims abstract description 80
- 239000004475 Arginine Substances 0.000 title claims abstract description 63
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 title claims abstract description 63
- 239000000203 mixture Substances 0.000 title claims abstract description 61
- 229930186147 Cephalosporin Natural products 0.000 title abstract description 8
- 229940124587 cephalosporin Drugs 0.000 title abstract description 8
- -1 cephalosporin acids Chemical class 0.000 title abstract description 8
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 title abstract description 4
- 229960000603 cefalotin Drugs 0.000 claims description 10
- 229960003866 cefaloridine Drugs 0.000 claims description 9
- CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 claims description 9
- JSDXOWVAHXDYCU-VXSYNFHWSA-N cefminox Chemical compound S([C@@H]1[C@@](C(N1C=1C(O)=O)=O)(NC(=O)CSC[C@@H](N)C(O)=O)OC)CC=1CSC1=NN=NN1C JSDXOWVAHXDYCU-VXSYNFHWSA-N 0.000 claims description 8
- XDZKBRJLTGRPSS-BGZQYGJUSA-N cefodizime Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(C)=C(CC(O)=O)S1 XDZKBRJLTGRPSS-BGZQYGJUSA-N 0.000 claims description 8
- GPRBEKHLDVQUJE-VINNURBNSA-N cefotaxime Chemical compound N([C@@H]1C(N2C(=C(COC(C)=O)CS[C@@H]21)C(O)=O)=O)C(=O)/C(=N/OC)C1=CSC(N)=N1 GPRBEKHLDVQUJE-VINNURBNSA-N 0.000 claims description 8
- 229960000433 latamoxef Drugs 0.000 claims description 8
- UQLLWWBDSUHNEB-CZUORRHYSA-N Cefaprin Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CSC1=CC=NC=C1 UQLLWWBDSUHNEB-CZUORRHYSA-N 0.000 claims description 6
- 229960004350 cefapirin Drugs 0.000 claims description 6
- 229960004366 ceftezole Drugs 0.000 claims description 6
- DZMVCVMFETWNIU-LDYMZIIASA-N ceftezole Chemical compound O=C([C@@H](NC(=O)CN1N=NN=C1)[C@H]1SC2)N1C(C(=O)O)=C2CSC1=NN=CS1 DZMVCVMFETWNIU-LDYMZIIASA-N 0.000 claims description 6
- JWCSIUVGFCSJCK-CAVRMKNVSA-N Disodium Moxalactam Chemical compound N([C@]1(OC)C(N2C(=C(CSC=3N(N=NN=3)C)CO[C@@H]21)C(O)=O)=O)C(=O)C(C(O)=O)C1=CC=C(O)C=C1 JWCSIUVGFCSJCK-CAVRMKNVSA-N 0.000 claims description 5
- VTLCNEGVSVJLDN-MLGOLLRUSA-N cefazedone Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3C=C(Cl)C(=O)C(Cl)=C3)[C@H]2SC1 VTLCNEGVSVJLDN-MLGOLLRUSA-N 0.000 claims description 5
- 229960002025 cefminox Drugs 0.000 claims description 5
- 229960001958 cefodizime Drugs 0.000 claims description 5
- GCFBRXLSHGKWDP-XCGNWRKASA-N cefoperazone Chemical compound O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC(O)=CC=1)C(=O)N[C@@H]1C(=O)N2C(C(O)=O)=C(CSC=3N(N=NN=3)C)CS[C@@H]21 GCFBRXLSHGKWDP-XCGNWRKASA-N 0.000 claims description 5
- 229960001991 ceftizoxime Drugs 0.000 claims description 5
- NNULBSISHYWZJU-LLKWHZGFSA-N ceftizoxime Chemical compound N([C@@H]1C(N2C(=CCS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 NNULBSISHYWZJU-LLKWHZGFSA-N 0.000 claims description 5
- 229960004755 ceftriaxone Drugs 0.000 claims description 5
- VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 claims description 5
- UHRBTBZOWWGKMK-DOMZBBRYSA-N flomoxef Chemical compound O([C@@H]1[C@@](C(N1C=1C(O)=O)=O)(NC(=O)CSC(F)F)OC)CC=1CSC1=NN=NN1CCO UHRBTBZOWWGKMK-DOMZBBRYSA-N 0.000 claims description 5
- 229960002878 flomoxef Drugs 0.000 claims description 5
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 229960005312 cefazedone Drugs 0.000 claims description 2
- 229960004682 cefoperazone Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- XIURVHNZVLADCM-IUODEOHRSA-N cefalotin Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CC1=CC=CS1 XIURVHNZVLADCM-IUODEOHRSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 45
- 159000000000 sodium salts Chemical class 0.000 abstract description 9
- 239000007924 injection Substances 0.000 abstract description 5
- 238000002347 injection Methods 0.000 abstract description 5
- 239000000843 powder Substances 0.000 abstract description 4
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 3
- 238000012856 packing Methods 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 230000003115 biocidal effect Effects 0.000 description 16
- 239000003242 anti bacterial agent Substances 0.000 description 14
- 229940088710 antibiotic agent Drugs 0.000 description 14
- 238000007599 discharging Methods 0.000 description 14
- 239000011521 glass Substances 0.000 description 14
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 13
- 229910052782 aluminium Inorganic materials 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical compound [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CC1=CC=CS1 VUFGUVLLDPOSBC-XRZFDKQNSA-M 0.000 description 9
- 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 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- AZZMGZXNTDTSME-JUZDKLSSSA-M cefotaxime sodium Chemical compound [Na+].N([C@@H]1C(N2C(=C(COC(C)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 AZZMGZXNTDTSME-JUZDKLSSSA-M 0.000 description 4
- NCFTXMQPRQZFMZ-WERGMSTESA-M Cefoperazone sodium Chemical compound [Na+].O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC(O)=CC=1)C(=O)N[C@@H]1C(=O)N2C(C([O-])=O)=C(CSC=3N(N=NN=3)C)CS[C@@H]21 NCFTXMQPRQZFMZ-WERGMSTESA-M 0.000 description 3
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229960002417 cefoperazone sodium Drugs 0.000 description 3
- 229960002727 cefotaxime sodium Drugs 0.000 description 3
- 229960000636 ceftizoxime sodium Drugs 0.000 description 3
- ADLFUPFRVXCDMO-LIGXYSTNSA-M ceftizoxime sodium Chemical compound [Na+].N([C@@H]1C(N2C(=CCS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 ADLFUPFRVXCDMO-LIGXYSTNSA-M 0.000 description 3
- 229960000479 ceftriaxone sodium Drugs 0.000 description 3
- 150000001780 cephalosporins Chemical class 0.000 description 3
- FDRNWTJTHBSPMW-GNXCPKRQSA-L disodium;(6r,7r)-7-[[(2e)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[(2-methyl-6-oxido-5-oxo-1,2,4-triazin-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound [Na+].[Na+].S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)/C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C([O-])=NN1C FDRNWTJTHBSPMW-GNXCPKRQSA-L 0.000 description 3
- GRIXGZQULWMCLU-HUTAOCTPSA-L disodium;(6r,7r)-7-[[2-carboxylato-2-(4-hydroxyphenyl)acetyl]amino]-7-methoxy-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound [Na+].[Na+].N([C@]1(OC)C(N2C(=C(CSC=3N(N=NN=3)C)CO[C@@H]21)C([O-])=O)=O)C(=O)C(C([O-])=O)C1=CC=C(O)C=C1 GRIXGZQULWMCLU-HUTAOCTPSA-L 0.000 description 3
- 229910001415 sodium ion Inorganic materials 0.000 description 3
- PPPZBOLFWGINKN-YLCXCWDSSA-M sodium;(6r,7r)-7-[[2-(difluoromethylsulfanyl)acetyl]amino]-3-[[1-(2-hydroxyethyl)tetrazol-5-yl]sulfanylmethyl]-7-methoxy-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound [Na+].O([C@@H]1[C@@](C(N1C=1C([O-])=O)=O)(NC(=O)CSC(F)F)OC)CC=1CSC1=NN=NN1CCO PPPZBOLFWGINKN-YLCXCWDSSA-M 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- VGEOUKPOQQEQSX-OALZAMAHSA-M cephapirin sodium Chemical compound [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CSC1=CC=NC=C1 VGEOUKPOQQEQSX-OALZAMAHSA-M 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- KPHCAENKLGZHCB-VQZRABBESA-M sodium;(6r,7r)-7-[[2-(3,5-dichloro-4-oxopyridin-1-yl)acetyl]amino]-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound [Na+].S1C(C)=NN=C1SCC1=C(C([O-])=O)N2C(=O)[C@@H](NC(=O)CN3C=C(Cl)C(=O)C(Cl)=C3)[C@H]2SC1 KPHCAENKLGZHCB-VQZRABBESA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- MMRINLZOZVAPDZ-LSGRDSQZSA-N (6r,7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[(1-methylpyrrolidin-1-ium-1-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;chloride Chemical compound Cl.S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1C[N+]1(C)CCCC1 MMRINLZOZVAPDZ-LSGRDSQZSA-N 0.000 description 1
- MCSJGXLZPITMIH-UHFFFAOYSA-N 2-aminobutane-1,1,1-triol Chemical class CCC(N)C(O)(O)O MCSJGXLZPITMIH-UHFFFAOYSA-N 0.000 description 1
- QYQDKDWGWDOFFU-IUODEOHRSA-N Cefotiam Chemical compound CN(C)CCN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CC=3N=C(N)SC=3)[C@H]2SC1 QYQDKDWGWDOFFU-IUODEOHRSA-N 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 230000004308 accommodation Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960002100 cefepime Drugs 0.000 description 1
- 229960003791 cefmenoxime Drugs 0.000 description 1
- HJJDBAOLQAWBMH-YCRCPZNHSA-N cefmenoxime Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NN=NN1C HJJDBAOLQAWBMH-YCRCPZNHSA-N 0.000 description 1
- 229960004261 cefotaxime Drugs 0.000 description 1
- 229960001242 cefotiam Drugs 0.000 description 1
- DKOQGJHPHLTOJR-WHRDSVKCSA-N cefpirome Chemical compound N([C@@H]1C(N2C(=C(C[N+]=3C=4CCCC=4C=CC=3)CS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 DKOQGJHPHLTOJR-WHRDSVKCSA-N 0.000 description 1
- 229960000466 cefpirome Drugs 0.000 description 1
- 229960000484 ceftazidime Drugs 0.000 description 1
- 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 description 1
- UCKZMPLVLCKKMO-LHLIQPBNSA-N cephamycin Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](C)[C@]21OC UCKZMPLVLCKKMO-LHLIQPBNSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229940081561 rocephin Drugs 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- KTAVBOYXMBQFGR-MAODNAKNSA-J tetrasodium;(6r,7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyimino-1-oxidoethylidene]amino]-3-[(2-methyl-5,6-dioxo-1h-1,2,4-triazin-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate;heptahydrate Chemical compound O.O.O.O.O.O.O.[Na+].[Na+].[Na+].[Na+].S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C([O-])=NN1C.S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C([O-])=NN1C KTAVBOYXMBQFGR-MAODNAKNSA-J 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a composition of arginine and a series of cephalosporin acids. Due to the adoption of the composition, the characteristic of high antibacterial activity of cephalosporin acids is kept, and the problems of poor solubility and weak acidity of cephalosporin acids are solved; and the composition is suitable for being directly packaged into a powder injection for injecting. According to prediction, the composition has higher stability than a corresponding sodium salt preparation, and has a certain clinical practical meaning.
Description
Technical field
The present invention relates to the compositions that the acid of arginine and a series of cephalo is formed, belong to field of medicine preparing technology.
Background technology
Cephalo-type antibiotics is one type of use antibiotics very widely; Cephalo acid is its active component; General water solublity is bad; Its sodium salt is as preparation so be widely used; The sodium salt that comprises cephalosporins such as cephalothin sodium, cefaloridine sodium, cefobutazine sodium, Refosporin (E.Merck)., cefapirin sodium, cefotaxime sodium, ceftriaxone sodium, cefoperazone sodium, Cefminox sodium, Cefodizime Sodium, ceftizoxime sodium, Latamoxef Sodium, 6315-S, it all is hydrolyzed into cephalo acid in vivo and works.
Cephalothin sodium, English common name: CEFALOTIN SODIUM is semisynthetic first generation cephalo-type antibiotics.
Cefaloridine sodium, English common name: CEFALORIDINE SODIUM is semisynthetic first generation cephalo-type antibiotics.
Cefobutazine sodium, English common name: CEFTEZOLE SODIUM is semisynthetic first generation cephalo-type antibiotics.
Refosporin (E.Merck)., English common name: CEFXOTIN SODIUM is semisynthetic first generation cephalo-type antibiotics.
Cefapirin sodium, English common name: CEPHAPIRIIN SODIUM is semisynthetic first generation cephalo-type antibiotics
Cefotaxime sodium has another name called cefotaxime, English common name: CEFOTAXIME SODIUM is semi-synthetic third generation cephalo-type antibiotics.
Ceftriaxone sodium has another name called rocephin, English common name: CEFTRIAXONE SODIUM is semisynthetic third generation cephalo-type rhzomorph.
Cefoperazone sodium, English common name: CEFOPERAZONE SODIUM is semisynthetic third generation cephalo-type antibiotics.
Cefminox sodium, English common name: CEFMINOX SODIUM, be the cephamycin derivant, antibacterial activity is close with third generation antibacterial cephalosporin element, also is classified as third generation cephalosporin.
Cefodizime Sodium, English common name: CEFODIZIME SODIUM is semisynthetic third generation cephalo-type antibiotics.
Ceftizoxime sodium, English common name: CEFTIZOXIME SODIUM is semisynthetic third generation cephalo-type antibiotics.
Latamoxef Sodium, English common name: LATAMOXEF SODIUM is semisynthetic oxacephems antibiotic.
6315-S, English common name: FLOMOXEF SODIUM is semisynthetic oxygen cephalosporins.
Cephalo-type antibiotics is because of the characteristics of its circulus; Relatively stable in sour environment, unstable in the alkaline environment, degrade easily; Because of its sodium salt is alkalescence and in salification process, also is in the alkaline environment, so the sodium salt that the cephalo acid ratio is formed by cephalo acid is more stable.
The acid of part cephalo or its salt, like ceftazidime, cefepime, cefpirome, cefotiam, cefmenoxime etc., water soluble, but it is acid, generally adds to use after sodium carbonate or arginine are regulated PH.
But the active ingredient cephalo of most of cephalo-type antibiotics is sour, and water solublity is bad.But because it is cephalo acid, acid group is arranged, be faintly acid, be dissolved in the water jointly after can making up with weakly alkaline arginine.
Wherein arginine plays hydrotropy and acid-alkali accommodation effect, can obtain neutral solution than faster with above-mentioned undissolved cephalo acid dissolving, and of light color, clarification, can directly be used for injection.
The active ingredient cephalo acid of 13 kinds of cephalo sodium salts such as aforementioned cephalothin sodium also can be used other cosolvent, like the sterile sodium carbonate that has commonly used.
But when using sodium carbonate, produce carbon dioxide during dissolving, use inconvenient; And dissolving the time causes the solution colour jaundice easily.This maybe be relevant with the existence of sodium carbonate exothermic dissolution and sodium ion.
And sodium carbonate belongs to inorganic salt, after the acid of the bigger and cephalo of proportion mixes, sinks to the bottom layering easily in case of shaking, and causes compositions inhomogeneous, and uniformity of dosage units is defective, and there is not this problem in arginine.
Patent CN200710026319.1 and CN200710026320.4 have introduced the organic amine salt and the amino butanetriol salt of serial cephalo, to replace the sodium salt of above-mentioned cephalo.Organic amine salt has wherein related to arginine salt.But it is through the new chemical compound of one-tenth salt formation, is essentially different with compositions of the present invention:
The present invention is the compositions that arginine and the acid of a series of cephalo are formed; Be that cephalo acid and arginine simple physical are mixed; What CN200710026319.1 and CN200710026320.4 introduced is cephalo and organic amine generation chemical reaction, has formed a kind of new organic amine salt of a series of cephalos.
Goal of the invention
The object of the present invention is to provide the compositions of arginine and the acid of a series of one group of cephalo, both kept the good antibiotic active characteristics of cephalo acid, solved again that cephalo acid is poorly soluble, the problem of slant acidity.Said composition is suitable for direct packaging and becomes powder ampoule agent for injection, adds the injection water or be dissolved in the infusion solutions to use.
Injection cephalo-type injectable powder by instance of the present invention (but being not limited to) makes can be distributed into single preparation easily, and it has good stable property, and it is than corresponding sodium salt preparation, and quality is more stable, and certain clinical practice meaning is arranged.
The present composition has solved the problem of active ingredient cephalo acid insoluble in water, adds arginine and makees cosolvent, can directly be dissolved in the aqueous solution and use; The sodium salt preparation of above-mentioned cephalo is widely used now, but all has the problem of less stable, estimates that the present invention can obviously improve the stability of product.
Above-mentioned composition also no longer contains sodium ion simultaneously, can cannot not be fit to suitablely absorb the special population use of sodium ion, and expectation can enlarge the scope of application of above-mentioned cephalo-type antibiotics.
Above-mentioned composition is two kinds of organic mixing, and proportion is more approaching, easy mix homogeneously, and can not make it layering evenly because of the external force effect; Cephalo acid simultaneously is because crystal formation is not so good, so after flowability poorly, adds arginine, can improve significantly, improve the flowability of mixture, thereby have the industrial value of good reality.
Summary of the invention
The present invention provides a kind of suitability for mass industrialized production, product quality height and more stable arginine and the sour compositions of a series of cephalo.
It is characterized in that: 1, the cephalo acid in the compositions comprises the acid of cephalothin acid, cefaloridine, ceftezole is sour, cefazedone is sour, cefapirin is sour, cefotaxime acid, ceftriaxone acid, cefoperazone is sour, cefminox is sour, Cefodizime is sour, ceftizoxime is sour, latamoxef is sour, flomoxef is sour.
2, compositions is the compositions that arginine and above-mentioned wherein a kind of cephalo acid combine, the compositions of forming like cefotaxime acid and arginine;
3, cephalo acid and arginic ratio in the compositions, its optimal proportion is that cephalo acid was formed with arginine in 1: 1 in molar ratio, it shows as different cephalo acid and arginine wt than different, but its optimal proportion is mol ratio 1: 1 after the process conversion.
4, the ratio of compositions can suitably be floated near 1: 1 optimal proportion of mol ratio, floats up or down in 10%, is suitably and the acceptable ratio.The appropriate molar ratios of compositions is: 09～1.1: 1.
The practical implementation step is following: in gnotobasis, take by weighing suitable aseptic arginine of granularity, proportion and cephalo acid sterile bulk drug according to the prescription ratio, pour in the mixer.Mix the powder operation according to aseptic mixed powder standard operating procedure, behind the mix homogeneously, discharging divides packing, is transferred to sterile preparation packing workshop then, is distributed into single by specification with antibiotic glass bottle and packs.
The specific embodiment
Further set forth the present invention through embodiment below, but do not limit the present invention.
The preparation of embodiment 1 cefotaxime acid arginine composition:
Get aseptic cefotaxime acid 45.5kg and aseptic arginine 17.4kg under the gnotobasis, put in the mixer behind the mix homogeneously discharging, Aluminum Drum packing.Be transferred to sterile preparation packing workshop then, be filled in the antibiotic glass bottle, get the preparation finished product by the specification branch.
| ? | Dissolubility | Mobile |
| Cefotaxime acid | Water insoluble | Fluffy, mobile poor, be not suitable for packing |
| The cefotaxime acid arginine | Dissolving | Tightr, better mobile, but packing |
The preparation of embodiment 2 ceftriaxones acid arginine composition:
Get aseptic ceftriaxone acid 63.9kg and aseptic arginine 17.4kg under the gnotobasis, put in the mixer behind the mix homogeneously, discharging, Aluminum Drum is packed.Be transferred to sterile preparation packing workshop then, be filled in the antibiotic glass bottle, get the preparation finished product by the specification branch.
| ? | Dissolubility | Mobile |
| Ceftriaxone acid | Water insoluble | Fluffy, mobile poor, be not suitable for packing |
| Ceftriaxone acid arginine | Dissolving | Tightr, better mobile, but packing |
The preparation of embodiment 3 cefoperazones acid arginine composition:
Get aseptic cefoperazone acid 64.5kg and aseptic arginine 17.4kg under the gnotobasis, put in the mixer behind the mix homogeneously, discharging, Aluminum Drum is packed.Be transferred to sterile preparation packing workshop then, be filled in the antibiotic glass bottle, get the preparation finished product by the specification branch.
| ? | Dissolubility | Mobile |
| Cefoperazone acid | Water insoluble | Fluffy, mobile poor, be not suitable for packing |
| Cefoperazone acid arginine | Dissolving | Tightr, better mobile, but packing |
The preparation of embodiment 4 cefminoxs acid arginine composition:
Get aseptic cefminox acid 64.5kg and aseptic arginine 17.4kg under the gnotobasis, put in the mixer behind the mix homogeneously, discharging, Aluminum Drum is packed.Be transferred to sterile preparation packing workshop then, be filled in the antibiotic glass bottle, get the preparation finished product by the specification branch.
| ? | Dissolubility | Mobile |
| Cefminox acid | Water insoluble | Fluffy, mobile poor, be not suitable for packing |
| Cefminox acid arginine | Dissolving | Tightr, better mobile, but packing |
The preparation of embodiment 5 Cefodizimes acid arginine composition:
Get aseptic Cefodizime acid 60.6kg and aseptic arginine 17.4kg under the gnotobasis, put in the mixer behind the mix homogeneously, discharging, Aluminum Drum is packed.Be transferred to sterile preparation packing workshop then, be filled in the antibiotic glass bottle, get the preparation finished product by the specification branch.
| ? | Dissolubility | Mobile |
| Cefodizime acid | Water insoluble | Fluffy, mobile poor, be not suitable for packing |
| Cefodizime acid arginine | Dissolving | Tightr, better mobile, but packing |
The preparation of embodiment 6 ceftizoximes acid arginine composition:
Get aseptic ceftizoxime acid 38.3kg and aseptic arginine 17.4kg under the gnotobasis, put in the mixer behind the mix homogeneously, discharging, Aluminum Drum is packed.Be transferred to sterile preparation packing workshop then, be filled in the antibiotic glass bottle, get the preparation finished product by the specification branch.
| ? | Dissolubility | Mobile |
| Ceftizoxime acid | Water insoluble | Fluffy, mobile poor, be not suitable for packing |
| Ceftizoxime acid arginine | Dissolving | Tightr, better mobile, but packing |
The sour arginine composition preparation of embodiment 7 latamoxefs:
Get aseptic latamoxef acid 54.4kg and aseptic arginine 17.4kg under the gnotobasis, put in the mixer behind the mix homogeneously, discharging, Aluminum Drum is packed.Be transferred to sterile preparation packing workshop then, be filled in the antibiotic glass bottle, get the preparation finished product by the specification branch.
| ? | Dissolubility | Mobile |
| Latamoxef acid | Water insoluble | Fluffy, mobile poor, be not suitable for packing |
| Latamoxef acid arginine | Dissolving | Tightr, better mobile, but packing |
The preparation of embodiment 8 flomoxefs acid arginine composition:
Get aseptic flomoxef acid 49.6kg and aseptic arginine 17.4kg under the gnotobasis, put in the mixer behind the mix homogeneously, discharging, Aluminum Drum is packed.Be transferred to sterile preparation packing workshop then, be filled in the antibiotic glass bottle, get the preparation finished product by the specification branch.
| ? | Dissolubility | Mobile |
| Flomoxef acid | Water insoluble | Fluffy, mobile poor, be not suitable for packing |
| Flomoxef acid arginine | Dissolving | Tightr, better mobile, but packing |
The preparation of embodiment 9 cephalothin acid arginine compositions:
Get aseptic cephalothin acid 41.8kg and aseptic arginine 17.4kg under the gnotobasis, put in the mixer behind the mix homogeneously discharging, Aluminum Drum packing.Be transferred to sterile preparation packing workshop then, be filled in the antibiotic glass bottle, get the preparation finished product by the specification branch.
| ? | Dissolubility | Mobile |
| Cephalothin acid | Water insoluble | Fluffy, mobile poor, be not suitable for packing |
| The cephalothin acid arginine | Dissolving | Tightr, better mobile, but packing |
The preparation of embodiment 10 cefaloridine acid arginine composition:
Get aseptic cefaloridine acid 43.8kg and aseptic arginine 17.4kg under the gnotobasis, put in the mixer behind the mix homogeneously, discharging, Aluminum Drum is packed.Be transferred to sterile preparation packing workshop then, be filled in the antibiotic glass bottle, get the preparation finished product by the specification branch.
| ? | Dissolubility | Mobile |
| Cefaloridine acid | Water insoluble | Fluffy, mobile poor, be not suitable for packing |
| Cefaloridine acid arginine | Dissolving | Tightr, better mobile, but packing |
The preparation of embodiment 11 ceftezoles acid arginine composition:
Get aseptic ceftezole acid 46.3kg and aseptic arginine 17.4kg under the gnotobasis, put in the mixer behind the mix homogeneously, discharging, Aluminum Drum is packed.Be transferred to sterile preparation packing workshop then, be filled in the antibiotic glass bottle, get the preparation finished product by the specification branch.
| ? | Dissolubility | Mobile |
| Ceftezole acid | Water insoluble | Fluffy, mobile poor, be not suitable for packing |
| Ceftezole acid arginine | Dissolving | Tightr, better mobile, but packing |
The preparation of embodiment 12 cefazedones acid arginine composition:
Get aseptic cefazedone acid 51.1kg and aseptic arginine 17.4kg under the gnotobasis, put in the mixer behind the mix homogeneously, discharging, Aluminum Drum is packed.Be transferred to sterile preparation packing workshop then, be filled in the antibiotic glass bottle, get the preparation finished product by the specification branch.
| ? | Dissolubility | Mobile |
| Cefazedone acid | Water insoluble | Fluffy, mobile poor, be not suitable for packing |
| Cefazedone acid arginine | Dissolving | Tightr, better mobile, but packing |
The preparation of embodiment 13 cefapirin acid arginine composition:
Get aseptic cefapirin acid 44.5kg and aseptic arginine 17.4kg under the gnotobasis, put in the mixer behind the mix homogeneously, discharging, Aluminum Drum is packed.Be transferred to sterile preparation packing workshop then, be filled in the antibiotic glass bottle, get the preparation finished product by the specification branch.
| ? | Dissolubility | Mobile |
| Cefapirin acid | Water insoluble | Fluffy, mobile poor, be not suitable for packing |
| Cefapirin acid arginine | Dissolving | Tightr, better mobile, but packing |
Claims (1)
1. the present invention provides a kind of suitability for mass industrialized production, product quality height and more stable arginine and the sour compositions of a series of cephalo.It is characterized in that:
1, the cephalo acid in the compositions comprises the acid of cephalothin acid, cefaloridine, ceftezole is sour, cefazedone is sour, cefapirin is sour, cefotaxime acid, ceftriaxone acid, cefoperazone is sour, cefminox is sour, Cefodizime is sour, ceftizoxime is sour, latamoxef is sour, flomoxef is sour.
2, compositions is the compositions that arginine and above-mentioned wherein a kind of cephalo acid combine, the compositions of forming like cefotaxime acid and arginine;
3, cephalo acid and arginic ratio in the compositions, its optimal proportion is that cephalo acid was formed with arginine in 1: 1 in molar ratio, it shows as different cephalo acid and arginine wt than different, but its optimal proportion is mol ratio 1: 1 after the process conversion.
4, the ratio of compositions can suitably be floated near 1: 1 optimal proportion of mol ratio, floats up or down in 10%, is suitably and the acceptable ratio.The appropriate molar ratios of compositions is: 09～1.1: 1.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101653443A (en) * | 2009-08-18 | 2010-02-24 | 长沙京天生物医药科技有限公司 | Composition of amino-cephalosporanic acid and arginine |
| CN101669956A (en) * | 2009-07-31 | 2010-03-17 | 长沙京天生物医药科技有限公司 | Composition of cefoxitin acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101036657A (en) * | 2006-03-15 | 2007-09-19 | 广州白云山天心制药股份有限公司 | Stable cefoperazone medicine prparation |
| CN101548977A (en) * | 2009-05-06 | 2009-10-07 | 苏州致君万庆药业有限公司 | Composition of cefmetazole acid |
| CN101669956A (en) * | 2009-07-31 | 2010-03-17 | 长沙京天生物医药科技有限公司 | Composition of cefoxitin acid |
| CN101647800A (en) * | 2009-08-10 | 2010-02-17 | 北京联木医药技术发展有限公司 | Combination of cefuroxime sodium |
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