CN1371691A - Concentrated clear solution containing macrolides drug for intraveenous injection after being dilnted - Google Patents
Concentrated clear solution containing macrolides drug for intraveenous injection after being dilnted Download PDFInfo
- Publication number
- CN1371691A CN1371691A CN 01108245 CN01108245A CN1371691A CN 1371691 A CN1371691 A CN 1371691A CN 01108245 CN01108245 CN 01108245 CN 01108245 A CN01108245 A CN 01108245A CN 1371691 A CN1371691 A CN 1371691A
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- Prior art keywords
- injection
- dilution
- concentrated clear
- intravenous
- reactive compound
- Prior art date
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- Granted
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- 239000000243 solution Substances 0.000 title claims abstract description 32
- 239000003814 drug Substances 0.000 title claims abstract description 25
- 239000007924 injection Substances 0.000 title claims description 20
- 238000002347 injection Methods 0.000 title claims description 20
- 239000003120 macrolide antibiotic agent Substances 0.000 title abstract 3
- 229940079593 drug Drugs 0.000 title description 4
- 229940041033 macrolides Drugs 0.000 title 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 32
- 150000001875 compounds Chemical class 0.000 claims abstract description 23
- 239000006184 cosolvent Substances 0.000 claims abstract description 11
- 235000019441 ethanol Nutrition 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims abstract description 7
- 229960003276 erythromycin Drugs 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 150000002596 lactones Chemical class 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 15
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 15
- 239000012895 dilution Substances 0.000 claims description 13
- 238000010790 dilution Methods 0.000 claims description 13
- 238000001990 intravenous administration Methods 0.000 claims description 10
- 239000012046 mixed solvent Substances 0.000 claims description 9
- 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 6
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 5
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 5
- 239000001630 malic acid Substances 0.000 claims description 5
- 235000011090 malic acid Nutrition 0.000 claims description 5
- 239000008215 water for injection Substances 0.000 claims description 5
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 229960005261 aspartic acid Drugs 0.000 claims description 4
- 239000000174 gluconic acid Substances 0.000 claims description 4
- 235000012208 gluconic acid Nutrition 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 4
- PWKSKIMOESPYIA-UHFFFAOYSA-N 2-acetamido-3-sulfanylpropanoic acid Chemical compound CC(=O)NC(CS)C(O)=O PWKSKIMOESPYIA-UHFFFAOYSA-N 0.000 claims description 3
- 239000004475 Arginine Substances 0.000 claims description 3
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 3
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 3
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- 229960005070 ascorbic acid Drugs 0.000 claims description 3
- 235000013922 glutamic acid Nutrition 0.000 claims description 3
- 239000004220 glutamic acid Substances 0.000 claims description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 2
- 239000004472 Lysine Substances 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 239000003708 ampul Substances 0.000 claims description 2
- 235000009697 arginine Nutrition 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims description 2
- 235000018977 lysine Nutrition 0.000 claims description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 2
- 235000008729 phenylalanine Nutrition 0.000 claims description 2
- 239000004033 plastic Substances 0.000 claims description 2
- 229920003023 plastic Polymers 0.000 claims description 2
- 239000001384 succinic acid Substances 0.000 claims description 2
- 235000011044 succinic acid Nutrition 0.000 claims description 2
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 abstract description 32
- 229960004099 azithromycin Drugs 0.000 abstract description 24
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 8
- 239000000463 material Substances 0.000 abstract description 3
- 235000011187 glycerol Nutrition 0.000 abstract 1
- 238000010253 intravenous injection Methods 0.000 abstract 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 16
- 229940090044 injection Drugs 0.000 description 12
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 8
- 239000004201 L-cysteine Substances 0.000 description 8
- 235000013878 L-cysteine Nutrition 0.000 description 8
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- 201000004813 Bronchopneumonia Diseases 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- 241000589248 Legionella Species 0.000 description 2
- 208000007764 Legionnaires' Disease Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000204031 Mycoplasma Species 0.000 description 2
- 208000019802 Sexually transmitted disease Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229940101006 anhydrous sodium sulfite Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000003385 bacteriostatic effect Effects 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 206010006451 bronchitis Diseases 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 206010022000 influenza Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000013618 particulate matter Substances 0.000 description 2
- 238000006303 photolysis reaction Methods 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 206010001076 Acute sinusitis Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010003757 Atypical pneumonia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 201000001178 Bacterial Pneumonia Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000606124 Bacteroides fragilis Species 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010007882 Cellulitis Diseases 0.000 description 1
- 229940123150 Chelating agent Drugs 0.000 description 1
- 208000007190 Chlamydia Infections Diseases 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
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- 229930010555 Inosine Natural products 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 241000588655 Moraxella catarrhalis Species 0.000 description 1
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- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
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- 208000001435 Thromboembolism Diseases 0.000 description 1
- 208000006374 Uterine Cervicitis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
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- 235000003704 aspartic acid Nutrition 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
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- 239000008121 dextrose Substances 0.000 description 1
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- 208000003512 furunculosis Diseases 0.000 description 1
- 229940093181 glucose injection Drugs 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
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- 229960003786 inosine Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229940080526 mannitol injection Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- -1 sodium sulfite Chemical compound 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The concentrated clear solution containing active compound macrolide medicine, component solvent, cosolvent and medicinal prescription auxiliary material is characterized by that the above-mentioned concentrated clear solution can be diluted for intravenous injection, the described macrolide medicine is 9-deoxy-9 alpha-aza-9 alpha-methyl-9 alpha-erythromycin A, Every millilitre of the concentrated solution contains 0.02-0.2 g of the described active compound, the described component solvent is a mixture formed from glycerine and ethyl alcohol. After the solution made of azithromycin is injected into the human body, it can directly produce anti-bacterial action.
Description
The present invention relates to the concentrated clear and bright solution of injection for intravenous after a kind of dilution that contains Macrocyclolactone lactone kind medicine, the reactive compound that wherein contains is a Macrocyclolactone lactone kind medicine, its chemistry 9-deoxidation by name-9 α-azepine-9 Alpha-Methyl-9 α-Erythromycin A (being azithromycin, English name Azithromycin).
In the prior art, Chinese patent 95106702.8 should be mentioned that water soluble Azithromycin salt and aqueous solution thereof obtain injectable powder after making aqueous injection and lyophilization after the dilution.This patent adds azithromycin, organic acid in the entry, make aqueous solution, concentrating under reduced pressure then, dry in exsiccator again, obtain water soluble Azithromycin salt, again its dissolving and dilution are made the water soluble Azithromycin salt aqueous injection for clinical use or make the water soluble Azithromycin salt injectable powder, dissolves with water for injection before the clinical use.Its equipment requirements height, complex operation, manufacturing cycle is long, efficient is low, a large amount of wastes of manpower, material resources, financial resources and time.The Macrocyclolactone lactone kind medicine injectable powder lumps after Long-term Storage, does not dissolve or dissolve and thoroughly do not cause the medicinal liquid unclarity, and particulate matter can surpass the regulation of standards of pharmacopoeia.And particulate matter enters vein blood vessel is to cause certain drug-induced disease such as lung tissue granuloma, the immediate cause of blood capillary thromboembolism etc.Patent 95106702.8 relates to makes aqueous injection with water soluble Azithromycin salt, this aqueous solution is extremely unsettled, and the carbon-oxygen bond on its lactonic ring very easily ruptures, and causes catabolite to exceed standard far away, as everyone knows, catabolite is the immediate cause that causes many medicine serious adverse reactions.
The object of the present invention is to provide the concentrated clear and bright solution of injection for intravenous after a kind of dilution that contains Macrocyclolactone lactone kind medicine, it directly makes azithromycin the concentrated clear and bright solution that use for the clinical vein injection dilution back, needn't face with preceding with water for injection with after the powder pin dissolving, redilution is in venous transfusion.
Technical scheme of the present invention is: the concentrated clear and bright solution of injection for intravenous after a kind of dilution that contains Macrocyclolactone lactone kind medicine comprises reactive compound Macrocyclolactone lactone kind medicine, mixed solvent, cosolvent and medicinal formula adjuvant; It is characterized in that: described Macrocyclolactone lactone kind medicine is that 9-deoxidation-9 α-azepine-9 Alpha-Methyl-9 α-Erythromycin A (is an azithromycin, English name Azithromycin), every milliliter of concentrated solution contains 0.02-0.2 and restrains described reactive compound, described mixed solvent is the mixture of mainly being made up of glycerol and ethanol, and the consumption of described fused solvent should be enough to make described reactive compound dissolving and keep stable.
The present invention compared with prior art has following advantage:
Water soluble Azithromycin salt is the derivant of azithromycin, be two kinds of different chemical compounds, what can directly bring into play antibacterial action in human body is azithromycin, and water soluble Azithromycin salt enters must decompose behind the human body and discharges azithromycin competence exertion effect then.What patent 95106702.8 related to is the preparation of the aqueous injection and the injectable powder of water soluble Azithromycin salt and water soluble salt thereof, and what the present invention relates to is the clear and bright solution of azithromycin.The present invention compares with patent 95106702.8, and patent 95106702.8 is that azithromycin is made water soluble salt, again salt is made preparation, be expelled to human body after, salt decomposes and discharges azithromycin, thereby realizes antibacterial effect.And this patent is directly made azithromycin solution, directly bring into play antibacterial action after being expelled to human body, and do not need to experience the loaded down with trivial details step of patent 95106702.8, do not need to waste a large amount of human and material resources, financial resources and time, and can have more direct final effect.
Medicinal formula adjuvant described in the technical scheme mainly comprises: antioxidant, anti-photodissociation agent, chelating agent, pH regulator agent.Described antioxidant can be selected for use from sodium pyrosulfite, sodium sulfite, anhydrous sodium sulfate, anti-photodissociation agent can be selected for use from guanosine, inosine, L-cysteine, and chelating agent can be selected for use from disodiumedetate, calcio-disodium edetate.The pH regulator agent can be selected from cosolvent, and the pH value of concentrated solution remains on 6.5-7.5, remains on the normal pH value scope of human body (about pH value 7.4), and is little to the acid-base balance influence of human body, little to the zest of human body.
In the described mixed solvent, glycerol and alcoholic acid mixed proportion are that ethanol accounts for 60-90%, and glycerol accounts for 40%-10%.
Described cosolvent is one of ascorbic acid, malic acid, L-aspartic acid, arginine, glutamic acid, gluconic acid, lysine, phenylalanine, L-cysteine, succinic acid or its mixture, the amount of used cosolvent is relevant with the molar concentration of described reactive compound, with respect to 1 mole reactive compound, add cosolvent 0.5-2.0 mole.
The dosage form of described solution is divided in ampoule bottle or other low capacity vial or the plastic bottle for preparing, and its bodge is 1-10ml, preferably 2-5ml.
Also contain one of propylene glycol, isopropyl alcohol, benzyl alcohol, Polyethylene Glycol, ethyl acetate, dimethyl acetylamide, water for injection, oil for injection or their mixture in the described mixed solvent.
Enumerate the prescription example of the clear and bright solution of some reactive compounds that the present invention relates to below, cited prescription example is in order to further explanation the present invention, and is not subjected to the restriction of these examples.
(1) azithromycin 100.0g
Benzyl benzoate 192.0ml
Disodiumedetate 0.2g
L-cysteine 0.8g
Oil for injection is an amount of
Total amount 1000.0ml
(2) azithromycin 200.0g
Aspartic acid 21.2g
Disodiumedetate 0.2g
Glycerol 80.0ml
Propylene glycol 100.0ml
Water for injection is an amount of
Total amount 1000.0ml
(3) azithromycin 100.0g
Arginine 10.9g
Disodiumedetate 0.2g
L-cysteine 0.5g
Isopropyl alcohol 100.0ml
Ethanol is an amount of
Total amount 1000.0ml
(4) azithromycin 200.0g
Glutamic acid 15.0g
L-cysteine 0.6g
Polyethylene Glycol 50.0ml
Propylene glycol 80.0ml
Ethanol is an amount of
Total amount 1000.0ml
(5) azithromycin 100.0g
Malic acid 12.1g
Disodiumedetate 0.2g
L-cysteine 0.5g
Anhydrous sodium sulfite 0.1g
Glycerol 100.0ml
Ethanol is an amount of
Total amount 1000.0ml
(6) azithromycin 200.0g
Malic acid 24.2g
Polyethylene Glycol 50.0ml
Isopropyl alcohol 80.0ml
Benzyl alcohol 50.0ml
Oil for injection is an amount of
Total amount 1000.0ml
(7) azithromycin 100.0g
Malic acid 5.0g
L-aspartic acid 8.2g
L-cysteine 0.8g
Propylene glycol 400.0ml
Ethanol is an amount of
Total amount 1000.0ml
(8) azithromycin 200.0g
Ascorbic acid 25.0g
Isopropyl alcohol 50.0ml
Benzyl alcohol 50.0ml
L-cysteine 0.6g
Disodiumedetate 0.2g
Glycerol is an amount of
Total amount 1000.0ml
(9) azithromycin 100.0g
Gluconic acid 15.0g
Disodiumedetate 0.2g
L-cysteine 0.6g
Glycerol 200.0ml
Ethanol is an amount of
Total amount 1000.0ml
(10) azithromycin 200.0g
Gluconic acid 30.0g
Disodiumedetate 0.2g
L-cysteine 0.8g
Glycerol 100.0ml
Ethanol is an amount of
Total amount 1000.0ml
The preparation of clear and bright solution of the present invention can be adopted the cold filter method of thermosol: earlier solvent is mixed in proportion, be heated to 60-80 ℃, again reactive compound, cosolvent and suitable pharmaceutic adjuvant are added in the mixed solvent, be stirred to dissolving fully, add proper amount of active carbon, be incubated 1-2 hour, filter, filtrate is cooled to room temperature with ice bath, leaves standstill about 24 hours, filters clear and bright once more.This technology can be protected positive preparation storage-stable, is particularly conducive to prevent sedimentary generation.
The concentrated clear and bright solution of the reactive compound that the present invention relates to can be diluted in various venous transfusions such as sodium chloride injection, ringer's solution, glucose injection, Dextrose and Sodium Chloride Inj., formula mannitol injection liquid, adopt the method that instils or inject, be applied to the prevention and the treatment of human body or the multiple infection of animal body.
The concentrated clear and bright solution of the reactive compound that the present invention relates to has characteristics such as has a broad antifungal spectrum, good effect, untoward reaction are few.Except that having gram positive bacteria had very strong antibacterial activity identical, can also suppress the escherichia coli of some other aerobic and anaerobism G-bacterium, especially hemophilus influenza and Enterobacter etc. with erythromycin.For other G-bacillus, has antibacterial activity as bacillus canalis capsulatus, Moraxella catarrhalis, bordetella pertussis, aerogenesis folder film clostridium, bacteroides fragilis etc.In addition, Neisseria gonorrheae and meningococcus also there is antibacterial activity.Although the existing bacteriostatic activity of Macrocyclolactone lactone kind medicine multilist, but the concentrated clear and bright solution of this reactive compound is except bacteriostatic activity, to micrococcus scarlatinae, streptococcus pneumoniae, hemophilus influenza, bacillus canalis capsulatus, escherichia coli, legionella pneumophilia etc., when being higher than 2-8 times of MIC, drug level can show bactericidal effect.
The concentrated clear and bright solution of the reactive compound that the present invention relates to, have unique pharmacokinetics and pharmacodynamic profiles, the intravenously administrable bioavailability can reach 100%, be distributed in tissue after the drug absorption at first rapidly, be slowly released into blood by tissue again, and then carry out the redistribution of medicine again, thus make 10-100 that tissue concentration is higher than serum-concentration doubly, apparently higher than the minimum inhibitory concentration of multiple encountered pathogenic bacteria clinically, and its T1/2 can reach 2-4 days, so sustainable several days of this high concentration.Reactive compound can also be absorbed rapidly by phagocyte and be carried into infection site, makes the tissue concentration of infection site higher, is more conducive to kill bacteria.
The concentrated clear and bright solution of the reactive compound that the present invention relates to, can be used in respiratory system infection clinically, as acute pharyngitis, tonsillitis, acute otitis media, acute sinusitis, acute bronchitis, acute episode of chronic bronchitis, atypical pneumonia, bacterial pneumonia; Urogenital and other sexually transmitted disease (STD) are as urethritis, cervicitis etc.; Skin soft-tissue infection is as cellulitis, erysipelas, furunculosis and impetigo etc.
The same with human body, effective too to the bacterial infection of other animal, be exemplified below:
Pig: escherichia coli diarrhoea, infection with legionella disease.
Cattle: diarrhoea, bronchopneumonia, mycoplasma and genital infection.
Horse: bronchopneumonia, mycoplasma, chlamydia infection, genito-urinary system infect.
Certainly, just enumerated the example of some diseases above, the concentrated clear and bright solution of the reactive compound that the present invention relates to can prevent and (or) treatment disease also never only refer to these.
Claims (6)
1, the concentrated clear and bright solution of injection for intravenous after a kind of dilution that contains Macrocyclolactone lactone kind medicine comprises reactive compound Macrocyclolactone lactone kind medicine, mixed solvent, cosolvent and medicinal formula adjuvant; It is characterized in that: described Macrocyclolactone lactone kind medicine is 9-deoxidation-9 α-azepine-9 Alpha-Methyl-9 α-Erythromycin A, every milliliter of concentrated solution contains 0.02-0.2 and restrains described reactive compound, described mixed solvent is the mixture of mainly being made up of glycerol and ethanol, and the consumption of described fused solvent should be enough to make described reactive compound dissolving and keep stable.
2. the concentrated clear and bright solution of injection for intravenous after the dilution that contains Macrocyclolactone lactone kind medicine according to claim 1, it is characterized in that: in the described mixed solvent, glycerol and alcoholic acid mixed proportion are that ethanol accounts for 60-90%, and glycerol accounts for 40%-10%.
3. the concentrated clear and bright solution of injection for intravenous after the dilution that contains Macrocyclolactone lactone kind medicine according to claim 1, it is characterized in that: described cosolvent is one of ascorbic acid, malic acid, L-aspartic acid, arginine, glutamic acid, gluconic acid, lysine, phenylalanine, L-cysteine, succinic acid or its mixture, the amount of used cosolvent is relevant with the molar concentration of described reactive compound, with respect to 1 mole reactive compound, add cosolvent 0.5-2.0 mole.
4. the concentrated clear and bright solution of injection for intravenous after the dilution that contains Macrocyclolactone lactone kind medicine according to claim 1, it is characterized in that: the dosage form of described solution is divided in ampoule bottle or other low capacity vial or the plastic bottle for preparing, and its bodge is 1-10ml.
5. the concentrated clear and bright solution of injection for intravenous after the dilution that contains Macrocyclolactone lactone kind medicine according to claim 4 is characterized in that: 2-5ml preferably.
6. the concentrated clear and bright solution of injection for intravenous is characterized in that: also contain one of propylene glycol, isopropyl alcohol, benzyl alcohol, Polyethylene Glycol, ethyl acetate, dimethyl acetylamide, water for injection, oil for injection or their mixture in the described mixed solvent after the dilution that contains Macrocyclolactone lactone kind medicine according to claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01108245 CN1194697C (en) | 2001-02-23 | 2001-02-23 | Concentrated clear solution containing macrolides drug for intraveenous injection after being dilnted |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01108245 CN1194697C (en) | 2001-02-23 | 2001-02-23 | Concentrated clear solution containing macrolides drug for intraveenous injection after being dilnted |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1371691A true CN1371691A (en) | 2002-10-02 |
| CN1194697C CN1194697C (en) | 2005-03-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 01108245 Expired - Lifetime CN1194697C (en) | 2001-02-23 | 2001-02-23 | Concentrated clear solution containing macrolides drug for intraveenous injection after being dilnted |
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| Country | Link |
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| CN (1) | CN1194697C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102755287A (en) * | 2012-07-20 | 2012-10-31 | 天津药业集团新郑股份有限公司 | Azithromycin oral liquid and preparation method thereof |
| CN104688676A (en) * | 2013-12-10 | 2015-06-10 | 沈阳药科大学 | Andrographolide concentrated liquid and medical application thereof |
-
2001
- 2001-02-23 CN CN 01108245 patent/CN1194697C/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102755287A (en) * | 2012-07-20 | 2012-10-31 | 天津药业集团新郑股份有限公司 | Azithromycin oral liquid and preparation method thereof |
| CN104688676A (en) * | 2013-12-10 | 2015-06-10 | 沈阳药科大学 | Andrographolide concentrated liquid and medical application thereof |
| CN104688676B (en) * | 2013-12-10 | 2018-03-30 | 沈阳药科大学 | Andrographolide concentrated type liquid formula and its medical usage |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1194697C (en) | 2005-03-30 |
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