CN1927854A - Preparation method of potassium sodium dehydroandroan drographolide succinate, potassium sodium dehydroandroan drographolide succinate preparation and preparation method thereof - Google Patents
Preparation method of potassium sodium dehydroandroan drographolide succinate, potassium sodium dehydroandroan drographolide succinate preparation and preparation method thereof Download PDFInfo
- Publication number
- CN1927854A CN1927854A CN 200510098407 CN200510098407A CN1927854A CN 1927854 A CN1927854 A CN 1927854A CN 200510098407 CN200510098407 CN 200510098407 CN 200510098407 A CN200510098407 A CN 200510098407A CN 1927854 A CN1927854 A CN 1927854A
- Authority
- CN
- China
- Prior art keywords
- preparation
- potassium sodium
- dehydroandroan drographolide
- drographolide succinate
- sodium dehydroandroan
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 58
- KYEPHZAHIRDQSR-SXASYTFBSA-L potassium;sodium;4-[[(1r,2r,4ar,5r,8as)-2-(3-carboxylatopropanoyloxy)-1,4a-dimethyl-6-methylidene-5-[(e)-2-(5-oxo-2h-furan-4-yl)ethenyl]-3,4,5,7,8,8a-hexahydro-2h-naphthalen-1-yl]methoxy]-4-oxobutanoate Chemical compound [Na+].[K+].C(/[C@@H]1C(=C)CC[C@H]2[C@@]1(C)CC[C@H]([C@]2(COC(=O)CCC([O-])=O)C)OC(=O)CCC([O-])=O)=C\C1=CCOC1=O KYEPHZAHIRDQSR-SXASYTFBSA-L 0.000 title claims description 51
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 54
- 238000006243 chemical reaction Methods 0.000 claims abstract description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 32
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 27
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims abstract description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000010438 heat treatment Methods 0.000 claims abstract description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 10
- 238000005886 esterification reaction Methods 0.000 claims abstract description 8
- 238000010992 reflux Methods 0.000 claims abstract description 7
- 235000015320 potassium carbonate Nutrition 0.000 claims abstract description 6
- 239000011736 potassium bicarbonate Substances 0.000 claims abstract description 5
- 235000015497 potassium bicarbonate Nutrition 0.000 claims abstract description 5
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims abstract description 5
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims abstract description 5
- 235000011118 potassium hydroxide Nutrition 0.000 claims abstract description 5
- BOJKULTULYSRAS-OTESTREVSA-N Andrographolide Chemical compound C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CCC1=C)(CO)C)\C=C1/[C@H](O)COC1=O BOJKULTULYSRAS-OTESTREVSA-N 0.000 claims abstract description 4
- ASLUCFFROXVMFL-UHFFFAOYSA-N andrographolide Natural products CC1(CO)C(O)CCC2(C)C(CC=C3/C(O)OCC3=O)C(=C)CCC12 ASLUCFFROXVMFL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims abstract description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 44
- 239000007924 injection Substances 0.000 claims description 30
- 238000002347 injection Methods 0.000 claims description 30
- 239000001384 succinic acid Substances 0.000 claims description 22
- 239000000843 powder Substances 0.000 claims description 18
- 238000005406 washing Methods 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical compound O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 claims description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- 238000002425 crystallisation Methods 0.000 claims description 8
- 230000008025 crystallization Effects 0.000 claims description 8
- 239000008215 water for injection Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 230000032050 esterification Effects 0.000 claims description 6
- 239000012535 impurity Substances 0.000 claims description 6
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 5
- 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 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 239000003463 adsorbent Substances 0.000 claims description 3
- 230000001476 alcoholic effect Effects 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 abstract description 9
- 230000003647 oxidation Effects 0.000 abstract description 9
- 238000007254 oxidation reaction Methods 0.000 abstract description 9
- YIIRVUDGRKEWBV-FZOOCBFYSA-N (3e)-3-[2-[(1r,4as,5r,6r,8as)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1h-naphthalen-1-yl]ethylidene]furan-2-one Chemical compound C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CCC1=C)(CO)C)\C=C1/C=COC1=O YIIRVUDGRKEWBV-FZOOCBFYSA-N 0.000 abstract 3
- XMJAJFVLHDIEHF-UHFFFAOYSA-N 14-deoxy-11, 12-didehydroandrographolide Natural products OCC1(C)C(O)CCC2(C)C1CCC(=C)C2C=CC1=CCOC1=O XMJAJFVLHDIEHF-UHFFFAOYSA-N 0.000 abstract 3
- XMJAJFVLHDIEHF-YSDSKTICSA-N dehydroandrographolide Natural products C([C@@H]1C(=C)CC[C@H]2[C@@]1(C)CC[C@@H](O)[C@]2(CO)C)=CC1=CCOC1=O XMJAJFVLHDIEHF-YSDSKTICSA-N 0.000 abstract 3
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 abstract 1
- 230000015556 catabolic process Effects 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- 229940014800 succinic anhydride Drugs 0.000 abstract 1
- 229940090044 injection Drugs 0.000 description 27
- 238000003756 stirring Methods 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- 238000001914 filtration Methods 0.000 description 14
- 239000003610 charcoal Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 229910052700 potassium Inorganic materials 0.000 description 9
- 239000011591 potassium Substances 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000000967 suction filtration Methods 0.000 description 8
- 238000009835 boiling Methods 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 238000001291 vacuum drying Methods 0.000 description 7
- YTHKMAIVPFVDNU-GPTWTFMPSA-N 4-[[(1r,2r,4ar,5r,8as)-2-(3-carboxypropanoyloxy)-1,4a-dimethyl-6-methylidene-5-[(e)-2-(5-oxo-2h-furan-4-yl)ethenyl]-3,4,5,7,8,8a-hexahydro-2h-naphthalen-1-yl]methoxy]-4-oxobutanoic acid Chemical compound C(/[C@@H]1C(=C)CC[C@H]2[C@@]1(C)CC[C@H]([C@]2(COC(=O)CCC(O)=O)C)OC(=O)CCC(O)=O)=C\C1=CCOC1=O YTHKMAIVPFVDNU-GPTWTFMPSA-N 0.000 description 6
- 229940105082 medicinal charcoal Drugs 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 229960004756 ethanol Drugs 0.000 description 5
- 238000004108 freeze drying Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000002594 sorbent Substances 0.000 description 5
- 238000010792 warming Methods 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 229960000935 dehydrated alcohol Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000006356 dehydrogenation reaction Methods 0.000 description 3
- -1 ester monopotassium salt Chemical class 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000007086 side reaction Methods 0.000 description 3
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 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
- 241000700605 Viruses Species 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229940093181 glucose injection Drugs 0.000 description 2
- 239000003978 infusion fluid Substances 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000005057 refrigeration Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000008354 sodium chloride injection Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010061695 Biliary tract infection Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108010064696 N,O-diacetylmuramidase Proteins 0.000 description 1
- 206010034038 Parotitis Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 210000004404 adrenal cortex Anatomy 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 208000003167 cholangitis Diseases 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000001723 curing Methods 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 238000005262 decarbonization Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000002596 lactones Chemical group 0.000 description 1
- 208000030208 low-grade fever Diseases 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 210000004493 neutrocyte Anatomy 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 206010044008 tonsillitis Diseases 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Medicinal Charcoal concentration (w/v) % | Potassium sodium dehydroandroan drographolide succinate content (%) | Clarity |
0 | 100% | Do not meet standard code |
0.01 | 99.8 | Do not meet standard code |
0.02 | 99.2 | Qualified |
0.03 | 98.9 | Qualified |
0.04 | 98.6 | Qualified |
0.05 | 97.1 | Qualified |
Time | Condition | Proterties | Clarity | Content (%) | Other |
0 | Faint yellow block | Qualified | 100.1 | Qualified | |
5 days | High temperature | Faint yellow block | Qualified | 99.8 | Qualified |
High light | Faint yellow block | Qualified | 99.4 | Qualified | |
10 days | High temperature | Faint yellow block | Qualified | 99.5 | Qualified |
High light | Faint yellow block | Qualified | 98.9 | Qualified |
The compatibility situation | The injection inflammation is bluffed rather | After adding 0.9% sodium chloride injection | After adding 5% glucose injection |
Proterties | Faint yellow block | Colourless clear liquid | Colourless clear liquid |
Drug content (%) before the compatibility | 100.1 | ||
Injection liquid pH value before the compatibility | 7.3 | 6.1 | 4.7 |
10 hours injection liquid ph values behind the compatibility | / | 6.3 | 5.0 |
10 hours clarity of injection behind the compatibility | Up to specification | Up to specification | Up to specification |
10 hours drug contents (%) behind the compatibility | / | 99.5 | 99.2 |
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2005100984073A CN100465171C (en) | 2005-09-06 | 2005-09-06 | Preparation method of potassium sodium dehydroandroan drographolide succinate, potassium sodium dehydroandroan drographolide succinate preparation and preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2005100984073A CN100465171C (en) | 2005-09-06 | 2005-09-06 | Preparation method of potassium sodium dehydroandroan drographolide succinate, potassium sodium dehydroandroan drographolide succinate preparation and preparation method thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1927854A true CN1927854A (en) | 2007-03-14 |
CN100465171C CN100465171C (en) | 2009-03-04 |
Family
ID=37858007
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB2005100984073A Active CN100465171C (en) | 2005-09-06 | 2005-09-06 | Preparation method of potassium sodium dehydroandroan drographolide succinate, potassium sodium dehydroandroan drographolide succinate preparation and preparation method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN100465171C (en) |
Cited By (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101270101B (en) * | 2008-05-08 | 2011-01-26 | 海南斯达制药有限公司 | Method for preparing potassium sodium dehydroandroan drographolide succinate for injection and its freeze-dried injection |
CN102030731A (en) * | 2010-12-28 | 2011-04-27 | 哈药集团三精制药股份有限公司 | Technique for preparing high-purity potassium sodium dehydroandroan drographolide succinate at low temperature by solvent crystallization |
CN102367243A (en) * | 2011-08-26 | 2012-03-07 | 贺金凤 | Stable potassium sodium dehydroandroan drographolide succinate compound and pharmaceutical composition thereof |
CN102382082A (en) * | 2011-09-07 | 2012-03-21 | 周晓东 | Novel potassium sodium dehydroandroan drographolide succinate compound and drug combination thereof |
CN101260098B (en) * | 2008-04-18 | 2012-05-02 | 长春迈灵生物工程有限公司 | Technique for preparing potassium sodium dehydroandroandrographolide succinate |
CN101260097B (en) * | 2008-04-18 | 2012-05-02 | 长春迈灵生物工程有限公司 | Technique for preparing potassium sodium dehydroandroandrographolide succinic by using potassium dehydroandrographolide succinate |
CN102552183A (en) * | 2012-02-02 | 2012-07-11 | 武汉长联来福制药股份有限公司 | Preparation method of potassium sodium dehydroaadroandrographolide succinate freeze-dried powder injection |
CN102584752A (en) * | 2011-12-27 | 2012-07-18 | 开封制药(集团)有限公司 | Preparation method of andrographolide bulk pharmaceutical |
CN102617527A (en) * | 2012-03-01 | 2012-08-01 | 湖北荷普药业股份有限公司 | Method for preparing potassium dehydroandrographolide succinate or potassium sodium dehydroandroan drographolide succinate |
CN102863408A (en) * | 2011-07-06 | 2013-01-09 | 重庆莱美药业股份有限公司 | Preparation method of andrographolide |
CN103113331A (en) * | 2013-02-28 | 2013-05-22 | 成都倍特药业有限公司 | Andrographolide synthetic method |
CN103113330A (en) * | 2013-02-28 | 2013-05-22 | 成都倍特药业有限公司 | Andrographolide salifying process |
CN104161729A (en) * | 2014-05-22 | 2014-11-26 | 杭州长典医药科技有限公司 | Special ultrafine potassium sodium dehydroandroandrographolide succinate powder preparation and preparation method thereof |
CN104208047A (en) * | 2014-09-19 | 2014-12-17 | 陈长潭 | Dry potassium sodium dehydroandrographolide succinate powder inhalation and preparation method thereof |
CN104744412A (en) * | 2015-04-07 | 2015-07-01 | 重庆药友制药有限责任公司 | Dehydroandrographolide succinate compound |
CN108503611A (en) * | 2018-05-31 | 2018-09-07 | 黑龙江珍宝岛药业股份有限公司鸡西分公司 | A kind of preparation method of andrographolide |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103735522B (en) * | 2013-12-30 | 2017-03-29 | 海南葫芦娃药业集团股份有限公司 | A kind of Yanhuning freeze dried powder for injection and preparation method thereof |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1169803C (en) * | 2000-12-07 | 2004-10-06 | 南阳市鹿城生化研究所 | Production process of high-purity chuanhuning |
CN1481813A (en) * | 2002-09-12 | 2004-03-17 | 贵州三力制药有限责任公司 | Injection fluid of f reeze-dry powder for allaying fever |
-
2005
- 2005-09-06 CN CNB2005100984073A patent/CN100465171C/en active Active
Cited By (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101260098B (en) * | 2008-04-18 | 2012-05-02 | 长春迈灵生物工程有限公司 | Technique for preparing potassium sodium dehydroandroandrographolide succinate |
CN101260097B (en) * | 2008-04-18 | 2012-05-02 | 长春迈灵生物工程有限公司 | Technique for preparing potassium sodium dehydroandroandrographolide succinic by using potassium dehydroandrographolide succinate |
CN101270101B (en) * | 2008-05-08 | 2011-01-26 | 海南斯达制药有限公司 | Method for preparing potassium sodium dehydroandroan drographolide succinate for injection and its freeze-dried injection |
CN102030731A (en) * | 2010-12-28 | 2011-04-27 | 哈药集团三精制药股份有限公司 | Technique for preparing high-purity potassium sodium dehydroandroan drographolide succinate at low temperature by solvent crystallization |
CN102030731B (en) * | 2010-12-28 | 2012-07-11 | 哈药集团三精制药股份有限公司 | Technique for preparing high-purity potassium sodium dehydroandroan drographolide succinate at low temperature by solvent crystallization |
CN102863408A (en) * | 2011-07-06 | 2013-01-09 | 重庆莱美药业股份有限公司 | Preparation method of andrographolide |
CN102863408B (en) * | 2011-07-06 | 2015-04-22 | 重庆莱美药业股份有限公司 | Preparation method of andrographolide |
CN102367243A (en) * | 2011-08-26 | 2012-03-07 | 贺金凤 | Stable potassium sodium dehydroandroan drographolide succinate compound and pharmaceutical composition thereof |
CN102367243B (en) * | 2011-08-26 | 2013-03-27 | 贺金凤 | Stable potassium sodium dehydroandroan drographolide succinate compound and pharmaceutical composition thereof |
CN102382082A (en) * | 2011-09-07 | 2012-03-21 | 周晓东 | Novel potassium sodium dehydroandroan drographolide succinate compound and drug combination thereof |
CN102382082B (en) * | 2011-09-07 | 2012-07-18 | 周晓东 | Novel potassium sodium dehydroandroan drographolide succinate compound and drug combination thereof |
CN102584752B (en) * | 2011-12-27 | 2014-05-14 | 开封制药(集团)有限公司 | Preparation method of andrographolide bulk pharmaceutical |
CN102584752A (en) * | 2011-12-27 | 2012-07-18 | 开封制药(集团)有限公司 | Preparation method of andrographolide bulk pharmaceutical |
CN102552183A (en) * | 2012-02-02 | 2012-07-11 | 武汉长联来福制药股份有限公司 | Preparation method of potassium sodium dehydroaadroandrographolide succinate freeze-dried powder injection |
CN102617527A (en) * | 2012-03-01 | 2012-08-01 | 湖北荷普药业股份有限公司 | Method for preparing potassium dehydroandrographolide succinate or potassium sodium dehydroandroan drographolide succinate |
CN103113331A (en) * | 2013-02-28 | 2013-05-22 | 成都倍特药业有限公司 | Andrographolide synthetic method |
CN103113330A (en) * | 2013-02-28 | 2013-05-22 | 成都倍特药业有限公司 | Andrographolide salifying process |
CN103113330B (en) * | 2013-02-28 | 2016-01-20 | 成都倍特药业有限公司 | Potassium Sodium Dehydroandroan drographolide Succinate salifying process |
CN104161729A (en) * | 2014-05-22 | 2014-11-26 | 杭州长典医药科技有限公司 | Special ultrafine potassium sodium dehydroandroandrographolide succinate powder preparation and preparation method thereof |
CN104208047A (en) * | 2014-09-19 | 2014-12-17 | 陈长潭 | Dry potassium sodium dehydroandrographolide succinate powder inhalation and preparation method thereof |
CN104744412A (en) * | 2015-04-07 | 2015-07-01 | 重庆药友制药有限责任公司 | Dehydroandrographolide succinate compound |
CN108503611A (en) * | 2018-05-31 | 2018-09-07 | 黑龙江珍宝岛药业股份有限公司鸡西分公司 | A kind of preparation method of andrographolide |
CN108503611B (en) * | 2018-05-31 | 2022-06-24 | 黑龙江珍宝岛药业股份有限公司鸡西分公司 | Preparation method of potassium sodium dehydroandroan drographolide succinate |
Also Published As
Publication number | Publication date |
---|---|
CN100465171C (en) | 2009-03-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN100465171C (en) | Preparation method of potassium sodium dehydroandroan drographolide succinate, potassium sodium dehydroandroan drographolide succinate preparation and preparation method thereof | |
CN101439022B (en) | Method for preparing clindamycin phosphate powder injection raw medicine | |
CN112870979B (en) | Separation and purification method of beta-nicotinamide mononucleotide | |
CN102382082B (en) | Novel potassium sodium dehydroandroan drographolide succinate compound and drug combination thereof | |
CN102367243B (en) | Stable potassium sodium dehydroandroan drographolide succinate compound and pharmaceutical composition thereof | |
CN101703484B (en) | Preparation method of hexadecadrol sodium phosphate freeze-dried powder injection | |
CN102643255B (en) | Andrographolide compound | |
CN103232449A (en) | Aztreonam compound, as well as preparation method and pharmaceutical composition thereof | |
CN106432276A (en) | Cefazolin sodium compound prepared according to novel intelligent crystallization technology and preparation of cefazolin sodium compound | |
CN102276533B (en) | New ozagrel sodium compound and medicinal composition thereof | |
CN103265561B (en) | Azlocillin sodium compound, its preparation method and pharmaceutical composition thereof | |
CN102358721B (en) | More stable aceglutamide compound and medicinal composition thereof | |
CN102367229B (en) | Ethylenediamine diaceturate compound and pharmaceutical composition thereof | |
RU2389498C1 (en) | Enterosorbent | |
CN109096129A (en) | A kind of preparation method of L-carnitine-L-tartrate | |
CN103232395A (en) | Sodium ozagrel compound, preparation method and drug composition thereof | |
CN113105326A (en) | Preparation method and application of aspirin lysine | |
CN1879613A (en) | Medicine containing galangin and preparation method thereof | |
CN103467492B (en) | Aspoxicillin compound, pharmaceutical composition, preparation and preparation method thereof | |
CN1234853C (en) | Production method of corn superoxide dismutase multienzyme | |
CN104844506A (en) | Medicinal pitavastatin calcium compound for treating hyperlipidemia | |
CN103131741A (en) | Biological modification method of active plant polyphenol substance molecules | |
CN114315897B (en) | Novel crystals of tedizolid phosphate and preparation method thereof | |
CN103980327B (en) | A kind of high-purity trehalose preparation method that can be used for pharmaceutical injection agent | |
CN110028077B (en) | Modified attapulgite, preparation method thereof and application thereof in pharmaceutical carrier |
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 | ||
EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Biochemical Pharmaceutical Factory of Zhuhai S.E.Z. Assignor: Huang Jinxiu Contract fulfillment period: 2009.12.18 to 2011.12.18 contract change Contract record no.: 2010990000047 Denomination of invention: Preparation method of potassium sodium dehydroandroan drographolide succinate, potassium sodium dehydroandroan drographolide succinate preparation and preparation method thereof Granted publication date: 20090304 License type: General permission Record date: 2010.1.27 |
|
LIC | Patent licence contract for exploitation submitted for record |
Free format text: COMMON LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2009.12.18 TO 2011.12.18; CHANGE OF CONTRACT Name of requester: THE BIOCHEMICAL PHARMACEUTICAL FACTORY OF ZHUHAI S Effective date: 20100127 |
|
EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Zhuhai Kinhoo Pharmaceutical Co.,Ltd. Assignor: Huang Jinxiu Contract record no.: 2010440001031 Denomination of invention: Preparation method of potassium sodium dehydroandroan drographolide succinate, potassium sodium dehydroandroan drographolide succinate preparation and preparation method thereof Granted publication date: 20090304 License type: Exclusive License Open date: 20070314 Record date: 20100727 |
|
EC01 | Cancellation of recordation of patent licensing contract |
Assignee: Zhuhai Kinhoo Pharmaceutical Co.,Ltd. Assignor: Huang Jinxiu Contract record no.: 2010440001031 Date of cancellation: 20120531 |
|
EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Biochemical Pharmaceutical Factory of Zhuhai S.E.Z. Assignor: Huang Jinxiu Contract record no.: 2012440000367 Denomination of invention: Preparation method of potassium sodium dehydroandroan drographolide succinate, potassium sodium dehydroandroan drographolide succinate preparation and preparation method thereof Granted publication date: 20090304 License type: Common License Open date: 20070314 Record date: 20120706 |
|
EC01 | Cancellation of recordation of patent licensing contract |
Assignee: Biochemical Pharmaceutical Factory of Zhuhai S.E.Z. Assignor: Huang Jinxiu Contract record no.: 2012440000367 Date of cancellation: 20141010 |
|
LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
EC01 | Cancellation of recordation of patent licensing contract |
Assignee: Biochemical Pharmaceutical Factory of Zhuhai S.E.Z. Assignor: Huang Jinxiu Contract record no.: 2010990000047 Date of cancellation: 20141117 |
|
EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20070314 Assignee: Biochemical Pharmaceutical Factory of Zhuhai S.E.Z. Assignor: Huang Jinxiu Contract record no.: 2014440000466 Denomination of invention: Preparation method of potassium sodium dehydroandroan drographolide succinate, potassium sodium dehydroandroan drographolide succinate preparation and preparation method thereof Granted publication date: 20090304 License type: Exclusive License Record date: 20141125 |
|
LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
EM01 | Change of recordation of patent licensing contract |
Change date: 20151204 Contract record no.: 2014440000466 Assignee after: Zhuhai homologous Pharmaceutical Co., Ltd. Assignee before: Biochemical Pharmaceutical Factory of Zhuhai S.E.Z. |
|
LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20180110 Address after: 519015 Guangdong city of Zhuhai province Jida West No. 209 Peace Industrial Center Building 2 floor Patentee after: Zhuhai morning Ann Pharmaceutical Co., Ltd. Address before: 519020 Guangdong city of Zhuhai province Gongbei road 30 four floor Patentee before: Huang Jinxiu |
|
TR01 | Transfer of patent right | ||
EM01 | Change of recordation of patent licensing contract | ||
EM01 | Change of recordation of patent licensing contract |
Change date: 20180308 Contract record no.: 2014440000466 Assignor after: Zhuhai morning Ann Pharmaceutical Co., Ltd. Assignor before: Huang Jinxiu |