CN101416956B - Ambroxol hydrochloride injection - Google Patents
Ambroxol hydrochloride injection Download PDFInfo
- Publication number
- CN101416956B CN101416956B CN2007100599696A CN200710059969A CN101416956B CN 101416956 B CN101416956 B CN 101416956B CN 2007100599696 A CN2007100599696 A CN 2007100599696A CN 200710059969 A CN200710059969 A CN 200710059969A CN 101416956 B CN101416956 B CN 101416956B
- Authority
- CN
- China
- Prior art keywords
- injection
- add
- ambroxol hydrochloride
- water
- sodium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 229960000985 ambroxol hydrochloride Drugs 0.000 title claims abstract description 79
- QNVKOSLOVOTXKF-UHFFFAOYSA-N 4-[(2-amino-3,5-dibromophenyl)methylamino]cyclohexan-1-ol;hydron;chloride Chemical compound Cl.NC1=C(Br)C=C(Br)C=C1CNC1CCC(O)CC1 QNVKOSLOVOTXKF-UHFFFAOYSA-N 0.000 title claims abstract description 78
- 239000007924 injection Substances 0.000 title claims abstract description 57
- 238000002347 injection Methods 0.000 title claims abstract description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 64
- 239000003381 stabilizer Substances 0.000 claims abstract description 25
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 13
- 239000004480 active ingredient Substances 0.000 claims abstract description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 72
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 60
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 44
- 239000008215 water for injection Substances 0.000 claims description 41
- 239000011780 sodium chloride Substances 0.000 claims description 30
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 23
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 14
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 14
- 229960000502 poloxamer Drugs 0.000 claims description 14
- 229920001983 poloxamer Polymers 0.000 claims description 14
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 14
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 12
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 12
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 12
- 229960005174 ambroxol Drugs 0.000 claims description 9
- JBDGDEWWOUBZPM-XYPYZODXSA-N ambroxol Chemical compound NC1=C(Br)C=C(Br)C=C1CN[C@@H]1CC[C@@H](O)CC1 JBDGDEWWOUBZPM-XYPYZODXSA-N 0.000 claims description 9
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 8
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 8
- 235000019800 disodium phosphate Nutrition 0.000 claims description 8
- 239000011736 potassium bicarbonate Substances 0.000 claims description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- 239000003814 drug Substances 0.000 abstract description 18
- 238000002360 preparation method Methods 0.000 abstract description 15
- 229940079593 drug Drugs 0.000 abstract description 10
- 230000003204 osmotic effect Effects 0.000 abstract description 9
- 239000000843 powder Substances 0.000 abstract description 9
- 239000000945 filler Substances 0.000 abstract description 7
- 239000000203 mixture Substances 0.000 abstract description 4
- 230000001105 regulatory effect Effects 0.000 abstract description 3
- 238000003860 storage Methods 0.000 abstract description 3
- 239000000969 carrier Substances 0.000 abstract 3
- 239000003978 infusion fluid Substances 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 57
- 229940090044 injection Drugs 0.000 description 44
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 28
- 229910052799 carbon Inorganic materials 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000000126 substance Substances 0.000 description 27
- 239000011859 microparticle Substances 0.000 description 21
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 14
- 238000012546 transfer Methods 0.000 description 13
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 12
- 229930195725 Mannitol Natural products 0.000 description 12
- 239000000594 mannitol Substances 0.000 description 12
- 235000010355 mannitol Nutrition 0.000 description 12
- 230000001954 sterilising effect Effects 0.000 description 12
- 238000004659 sterilization and disinfection Methods 0.000 description 12
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 9
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 9
- 229920002125 Sokalan® Polymers 0.000 description 9
- 229960001631 carbomer Drugs 0.000 description 9
- 238000005261 decarburization Methods 0.000 description 8
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 229920002307 Dextran Polymers 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000001802 infusion Methods 0.000 description 6
- 239000012982 microporous membrane Substances 0.000 description 6
- 238000012856 packing Methods 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000007710 freezing Methods 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000013618 particulate matter Substances 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 206010036790 Productive cough Diseases 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- 206010062717 Increased upper airway secretion Diseases 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 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 3
- 206010006451 bronchitis Diseases 0.000 description 3
- 229930182830 galactose Natural products 0.000 description 3
- 239000003580 lung surfactant Substances 0.000 description 3
- 210000003097 mucus Anatomy 0.000 description 3
- 208000026435 phlegm Diseases 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229940093181 glucose injection Drugs 0.000 description 2
- 230000000420 mucociliary effect Effects 0.000 description 2
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 2
- 239000008354 sodium chloride injection Substances 0.000 description 2
- 208000024794 sputum Diseases 0.000 description 2
- 210000003802 sputum Anatomy 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000005696 Diammonium phosphate Substances 0.000 description 1
- 206010062530 Increased bronchial secretion Diseases 0.000 description 1
- -1 PH regulator Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000002588 alveolar type II cell Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000004799 bromophenyl group Chemical group 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 208000034209 congenital alveolar dysplasia Diseases 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 229910000388 diammonium phosphate Inorganic materials 0.000 description 1
- 235000019838 diammonium phosphate Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 208000017574 dry cough Diseases 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
Condition | Project | Embodiment 1 | Embodiment 4 | Embodiment 7 | Embodiment 10 | Embodiment 13 |
Room temperature 0 month | Related substance | 0.18 | 0.12 | 0.15 | 0.17 | 0.14 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Particulate matter | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 3.98 | 4.02 | 4.08 | 4.10 | 4.02 | |
Room temperature 3 months | Related substance | 0.20 | 0.14 | 0.13 | 0.15 | 0.16 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.05 | 4.07 | 4.03 | 4.08 | 4.06 | |
Room temperature 6 months | Related substance | 0.23 | 0.15 | 0.16 | 0.14 | 0.15 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.15 | 4.10 | 4.05 | 4.05 | 4.07 | |
Room temperature 9 months | Related substance | 0.29 | 0.20 | 0.18 | 0.19 | 0.16 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.20 | 4.12 | 4.09 | 4.07 | 4.06 | |
Room temperature 12 months | Related substance | 0.32 | 0.21 | 0.20 | 0.18 | 0.19 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.28 | 4.10 | 4.07 | 4.10 | 4.08 | |
Room temperature 18 months | Related substance | 0.35 | 0.22 | 0.21 | 0.23 | 0.20 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.50 | 4.15 | 4.10 | 4.13 | 4.15 | |
Room temperature 24 months | Related substance | 0.35 | 0.22 | 0.21 | 0.23 | 0.20 |
Visible foreign matters | Foreign body is arranged | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.85 | 4.18 | 4.16 | 4.15 | 4.18 | |
Room temperature 36 months | Related substance | 0.42 | 0.24 | 0.25 | 0.27 | 0.22 |
Visible foreign matters | Foreign body is arranged | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 5.02 | 4.18 | 4.16 | 4.15 | 4.18 |
Condition | Project | Embodiment 2 | Embodiment 5 | Embodiment 8 | Embodiment 11 | Embodiment 14 |
Room temperature 0 month | Related substance | 0.16 | 0.14 | 0.13 | 0.12 | 0.13 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Particulate matter | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.03 | 4.06 | 4.07 | 4.11 | 4.06 | |
Room temperature 3 months | Related substance | 0.23 | 0.15 | 0.14 | 0.15 | 0.16 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.02 | 4.04 | 4.02 | 4.07 | 4.05 | |
Room temperature 6 months | Related substance | 0.23 | 0.15 | 0.16 | 0.14 | 0.15 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.21 | 4.05 | 4.04 | 4.06 | 4.08 | |
Room temperature 9 months | Related substance | 0.30 | 0.16 | 0.17 | 0.18 | 0.19 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.22 | 4.06 | 4.08 | 4.04 | 4.09 | |
Room temperature 12 months | Related substance | 0.31 | 0.17 | 0.21 | 0.19 | 0.18 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.30 | 4.12 | 4.10 | 4.12 | 4.09 | |
Room temperature 18 months | Related substance | 0.34 | 0.19 | 0.20 | 0.21 | 0.25 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.57 | 4.13 | 4.12 | 4.14 | 4.17 | |
Room temperature 24 months | Related substance | 0.38 | 0.21 | 0.20 | 0.21 | 0.23 |
Visible foreign matters | Foreign body is arranged | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.89 | 4.11 | 4.17 | 4.17 | 4.20 | |
Room temperature 36 months | Related substance | 0.41 | 0.20 | 0.21 | 0.28 | 0.23 |
Visible foreign matters | Foreign body is arranged | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 5.10 | 4.10 | 4.14 | 4.12 | 4.19 |
Condition | Project | Embodiment 3 | Embodiment 6 | Embodiment 9 | Embodiment 12 | Embodiment 15 |
Room temperature 0 month | Related substance | 0.14 | 0.11 | 0.14 | 0.18 | 0.16 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Particulate matter | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.05 | 4.01 | 4.05 | 4.17 | 4.12 | |
Room temperature 3 months | Related substance | 0.24 | 0.18 | 0.16 | 0.17 | 0.14 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification |
PH value | 4.08 | 4.04 | 4.08 | 4.07 | 4.06 | |
Room temperature 6 months | Related substance | 0.28 | 0.16 | 0.18 | 0.16 | 0.15 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.15 | 4.10 | 4.05 | 4.05 | 4.07 | |
Room temperature 9 months | Related substance | 0.29 | 0.20 | 0.18 | 0.19 | 0.16 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.28 | 4.11 | 4.10 | 4.09 | 4.08 | |
Room temperature 12 months | Related substance | 0.35 | 0.20 | 0.24 | 0.23 | 0.21 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.28 | 4.10 | 4.07 | 4.10 | 4.08 | |
Room temperature 18 months | Related substance | 0.35 | 0.22 | 0.21 | 0.23 | 0.20 |
Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.61 | 4.12 | 4.10 | 4.15 | 4.11 | |
Room temperature 24 months | Related substance | 0.39 | 0.21 | 0.26 | 0.28 | 0.23 |
Visible foreign matters | Foreign body is arranged | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 4.91 | 4.14 | 4.18 | 4.16 | 4.14 | |
Room temperature 36 months | Related substance | 0.45 | 0.23 | 0.27 | 0.26 | 0.25 |
Visible foreign matters | Foreign body is arranged | Up to specification | Up to specification | Up to specification | Up to specification | |
Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
PH value | 5.32 | 4.17 | 4.18 | 4.17 | 4.15 |
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2007100599696A CN101416956B (en) | 2007-10-22 | 2007-10-22 | Ambroxol hydrochloride injection |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2007100599696A CN101416956B (en) | 2007-10-22 | 2007-10-22 | Ambroxol hydrochloride injection |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101416956A CN101416956A (en) | 2009-04-29 |
CN101416956B true CN101416956B (en) | 2011-03-16 |
Family
ID=40628082
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2007100599696A Active CN101416956B (en) | 2007-10-22 | 2007-10-22 | Ambroxol hydrochloride injection |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101416956B (en) |
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101627967B (en) * | 2009-08-03 | 2011-12-28 | 上海华源药业(宁夏)沙赛制药有限公司 | Ambroxol hydrochloride liquid preparation and preparation method thereof |
CN101836952B (en) * | 2010-06-09 | 2012-03-14 | 云南龙海天然植物药业有限公司 | Ambroxol injection and preparation method thereof |
CN101836953B (en) * | 2010-06-12 | 2011-08-17 | 山东罗欣药业股份有限公司 | Ambroxol hydrochloride composition injection |
CN102552119B (en) * | 2010-12-28 | 2013-08-07 | 四川科伦药物研究有限公司 | Ambroxol hydrochloride glucose injection and preparation method thereof |
CN102153482B (en) * | 2011-02-28 | 2013-04-03 | 天津市铭泰医药科技有限公司 | Method for refining injection-level ambroxol hydrochloride, product and injection thereof |
CN102225049B (en) * | 2011-06-17 | 2012-11-21 | 成都百裕科技制药有限公司 | Preparation method of ambroxol hydrochloride injection with stable pH value |
CN103006548B (en) * | 2011-09-28 | 2015-10-07 | 四川科伦药物研究有限公司 | Ambroxol hydrochloride glucose injection and preparation method thereof |
CN102429879B (en) * | 2011-11-29 | 2013-05-29 | 海南灵康制药有限公司 | Ambroxol hydrochloride liposome injection |
CN102872462B (en) * | 2012-10-26 | 2013-04-17 | 山东罗欣药业股份有限公司 | Ambroxol hydrochloride composition and preparation thereof |
CN102988281A (en) * | 2012-12-11 | 2013-03-27 | 辽宁科泰生物基因制药股份有限公司 | Injection of ambroxol hydrochloride and preparation method thereof |
CN103393593B (en) * | 2013-08-02 | 2014-09-10 | 海南灵康制药有限公司 | Pharmaceutical composition containing ambroxol hydrochloride and fructose |
CN103505423B (en) * | 2013-09-10 | 2016-01-20 | 马鞍山丰原制药有限公司 | Bisolvon lyophilized injectable powder and preparation method thereof |
CN104771358A (en) * | 2014-01-14 | 2015-07-15 | 江苏柯菲平医药股份有限公司 | Acebrophylline injection and preparation method thereof |
CN104840417A (en) * | 2015-04-30 | 2015-08-19 | 济南康和医药科技有限公司 | Ambroxol hydrochloride injection and preparation method thereof |
CN105326790B (en) * | 2015-12-08 | 2018-06-05 | 青岛正大海尔制药有限公司 | The preparation method of ambroxol albuterol solution agent |
CN105326805B (en) * | 2015-12-08 | 2018-06-12 | 青岛正大海尔制药有限公司 | The preparation method of ambroxol salbutamol dripping pill |
CN105326815B (en) * | 2015-12-08 | 2018-06-01 | 青岛正大海尔制药有限公司 | The preparation method of ambroxol salbutamol controlled release capsule |
CN105326789B (en) * | 2015-12-08 | 2018-06-05 | 青岛正大海尔制药有限公司 | Ambroxol albuterol solution agent |
CN105326796B (en) * | 2015-12-08 | 2018-06-05 | 青岛正大海尔制药有限公司 | Ambroxol salbutamol powder |
CN105434412A (en) * | 2015-12-08 | 2016-03-30 | 青岛正大海尔制药有限公司 | Ambroxol and salbutamol controlled release capsule |
CN105456221B (en) * | 2015-12-08 | 2018-06-05 | 青岛正大海尔制药有限公司 | The preparation method of ambroxol salbutamol enteric coated particles |
CN105326804B (en) * | 2015-12-08 | 2018-06-05 | 青岛正大海尔制药有限公司 | Ambroxol salbutamol dripping pill |
CN105456201B (en) * | 2015-12-08 | 2018-06-01 | 青岛正大海尔制药有限公司 | The preparation method of ambroxol salbutamol pellet |
CN106074373A (en) * | 2016-08-18 | 2016-11-09 | 黑龙江中桂制药有限公司 | A kind of preparation method of Ambroxol Hydrochloride Glucose Injection |
CN106667902B (en) * | 2016-12-31 | 2020-06-02 | 辰欣药业股份有限公司 | Stable ambroxol hydrochloride injection and preparation method thereof |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1954808A (en) * | 2005-10-27 | 2007-05-02 | 常州市第四制药厂有限公司 | High dose Ambroxol hydrochloride freeze-dried preparation and preparation method |
-
2007
- 2007-10-22 CN CN2007100599696A patent/CN101416956B/en active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1954808A (en) * | 2005-10-27 | 2007-05-02 | 常州市第四制药厂有限公司 | High dose Ambroxol hydrochloride freeze-dried preparation and preparation method |
Also Published As
Publication number | Publication date |
---|---|
CN101416956A (en) | 2009-04-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101416956B (en) | Ambroxol hydrochloride injection | |
CN100372534C (en) | Torasemide freeze-drying preparation and prepn. method | |
CN103893258A (en) | Oral solid preparation containing desmodium styracifolium general flavone and application thereof | |
CN101935099A (en) | Composition for purifying water quality and preparation method thereof | |
CN102860980A (en) | Method for preparing rocuronium bromide injection | |
CN101088492B (en) | Stable supersaturated gemcitabine hydrochloride solution and its preparation process | |
CN102872462B (en) | Ambroxol hydrochloride composition and preparation thereof | |
CN108261398A (en) | A kind of injection pharmaceutical preparation containing Levosimendan and preparation method thereof | |
CN100389767C (en) | Injectable stable pharmaceutical composition containing active ingredient silibinin and its salt | |
CN102349893A (en) | Edaravone pharmaceutical composition | |
CN101554370B (en) | Syringin for injection, preparation method and application thereof | |
CN101822822A (en) | Drug composition of pramlintide and preparation method thereof | |
CN104645334B (en) | N acetylcysteine activated carbon composites and its preparation method and application | |
CN104887689A (en) | Medicine composition containing ambroxol hydrochloride and fructose | |
CN103006550A (en) | Citicoline sodium injection and preparation method thereof | |
CN102871961B (en) | Injection containing tirofiban | |
CN101491495A (en) | Salvianolic acid B magnesium injection, preparation method and use thereof | |
CN103536551A (en) | Fluorouracil composition freeze-dried powder for injection | |
CN102138925B (en) | Tigecycline composition and preparation method thereof | |
CN101129329A (en) | Injection containing huperzine for sulci venosi and method of preparing the same | |
CN103393685B (en) | Pharmaceutical composition containing oxaliplatin and fluorouracil | |
CN101697973B (en) | Cefathiamidine preparation for injection and preparation method thereof | |
CN1537530A (en) | Unit dosage type compound cantharis acid powder-injection, and its prepn. method | |
CN1813744A (en) | Method for preparing levogatifloxacin formulation for intravenous injection and formulation using same | |
CN1843504B (en) | Albumin nanosphere medicine composition and its preparation method and application method |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
ASS | Succession or assignment of patent right |
Owner name: TIANJIN PRECEDE MEDICAL TRADE CO., LTD. Free format text: FORMER OWNER: KANGHONG MEDICINE TECH DEVELOPMENT CO., LTD., TIANJIN Effective date: 20110727 |
|
C41 | Transfer of patent application or patent right or utility model | ||
COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 300193 NANKAI, TIANJIN TO: 300574 BINHAI NEW DISTRICT, TIANJIN |
|
TR01 | Transfer of patent right |
Effective date of registration: 20110727 Address after: 300574 building 3, No. 66 Dongting Road, Tianjin Development Zone, 406 Patentee after: Tianjin Purisen Medicine Trade Co.,Ltd. Address before: 300193 Tianjin City, Nankai District Anshan West Road No. 308 Patentee before: Tianjin Kanghong Pharmaceutical Science and Technology Development Co.,Ltd. |
|
C56 | Change in the name or address of the patentee |
Owner name: TIANJIN KANGZHE PHARMACEUTICAL TECHNOLOGY DEVELOPM Free format text: FORMER NAME: TIANJIN PRECEDE MEDICAL TRADE CO., LTD. |
|
CP01 | Change in the name or title of a patent holder |
Address after: 300574 building 3, No. 66 Dongting Road, Tianjin Development Zone, 406 Patentee after: Tianjin wisdom pharmaceutical science and Technology Development Co.,Ltd. Address before: 300574 building 3, No. 66 Dongting Road, Tianjin Development Zone, 406 Patentee before: Tianjin Purisen Medicine Trade Co.,Ltd. |
|
EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20090429 Assignee: TIANJIN INSTITUTE OF PHARMACEUTICAL RESEARCH PHARMACEUTICAL RESPONSIBLE CO.,LTD. Assignor: Tianjin wisdom pharmaceutical science and Technology Development Co.,Ltd. Contract record no.: 2012990000894 Denomination of invention: Ambroxol hydrochloride injection Granted publication date: 20110316 License type: Exclusive License Record date: 20121218 |
|
LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
CP03 | Change of name, title or address | ||
CP03 | Change of name, title or address |
Address after: Room 215-218, Floor 2, Building D, Comprehensive Service Area, Nangang Industrial Zone, 300000 Binhai New Area Development Zone, Tianjin Patentee after: Tianjin Kangzheweisheng Pharmaceutical Technology Development Co.,Ltd. Address before: 300574 406, Building 3, No. 66, Dongting Road, Tianjin Development Zone Patentee before: Tianjin wisdom pharmaceutical science and Technology Development Co.,Ltd. |