CN100370252C - Method for controlling quality of injection liquid or powder of - Google Patents
Method for controlling quality of injection liquid or powder of Download PDFInfo
- Publication number
- CN100370252C CN100370252C CNB2005100900434A CN200510090043A CN100370252C CN 100370252 C CN100370252 C CN 100370252C CN B2005100900434 A CNB2005100900434 A CN B2005100900434A CN 200510090043 A CN200510090043 A CN 200510090043A CN 100370252 C CN100370252 C CN 100370252C
- Authority
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- China
- Prior art keywords
- injection
- solution
- powder
- qingkailing
- add
- 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.)
- Expired - Fee Related
Links
- 238000002347 injection Methods 0.000 title claims abstract description 106
- 239000007924 injection Substances 0.000 title claims abstract description 106
- 239000000843 powder Substances 0.000 title claims abstract description 95
- 239000007788 liquid Substances 0.000 title claims abstract description 69
- 238000000034 method Methods 0.000 title claims abstract description 40
- 239000000243 solution Substances 0.000 claims abstract description 110
- 239000008923 Qingkailing Substances 0.000 claims abstract description 57
- IPQKDIRUZHOIOM-UHFFFAOYSA-N Oroxin A Natural products OC1C(O)C(O)C(CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IPQKDIRUZHOIOM-UHFFFAOYSA-N 0.000 claims abstract description 30
- IKIIZLYTISPENI-ZFORQUDYSA-N baicalin Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IKIIZLYTISPENI-ZFORQUDYSA-N 0.000 claims abstract description 30
- 229960003321 baicalin Drugs 0.000 claims abstract description 30
- AQHDANHUMGXSJZ-UHFFFAOYSA-N baicalin Natural products OC1C(O)C(C(O)CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 AQHDANHUMGXSJZ-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000003908 quality control method Methods 0.000 claims abstract description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 104
- 239000000706 filtrate Substances 0.000 claims description 62
- 238000012360 testing method Methods 0.000 claims description 42
- 239000013558 reference substance Substances 0.000 claims description 33
- 239000000047 product Substances 0.000 claims description 31
- 238000001914 filtration Methods 0.000 claims description 18
- 238000001514 detection method Methods 0.000 claims description 13
- 238000010812 external standard method Methods 0.000 claims description 13
- 239000012982 microporous membrane Substances 0.000 claims description 13
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 6
- 239000012085 test solution Substances 0.000 claims description 5
- 238000004811 liquid chromatography Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 50
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 abstract description 29
- 239000004380 Cholic acid Substances 0.000 abstract description 29
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 abstract description 29
- 229960002471 cholic acid Drugs 0.000 abstract description 29
- 235000019416 cholic acid Nutrition 0.000 abstract description 29
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 abstract description 29
- DGABKXLVXPYZII-SIBKNCMHSA-N hyodeoxycholic acid Chemical compound C([C@H]1[C@@H](O)C2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 DGABKXLVXPYZII-SIBKNCMHSA-N 0.000 abstract description 27
- CWVRJTMFETXNAD-FWCWNIRPSA-N 3-O-Caffeoylquinic acid Natural products O[C@H]1[C@@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-FWCWNIRPSA-N 0.000 abstract description 22
- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 abstract description 22
- CWVRJTMFETXNAD-KLZCAUPSSA-N Neochlorogenin-saeure Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-KLZCAUPSSA-N 0.000 abstract description 22
- CWVRJTMFETXNAD-JUHZACGLSA-N chlorogenic acid Chemical compound O[C@@H]1[C@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-JUHZACGLSA-N 0.000 abstract description 22
- 229940074393 chlorogenic acid Drugs 0.000 abstract description 22
- FFQSDFBBSXGVKF-KHSQJDLVSA-N chlorogenic acid Natural products O[C@@H]1C[C@](O)(C[C@@H](CC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O FFQSDFBBSXGVKF-KHSQJDLVSA-N 0.000 abstract description 22
- 235000001368 chlorogenic acid Nutrition 0.000 abstract description 22
- BMRSEYFENKXDIS-KLZCAUPSSA-N cis-3-O-p-coumaroylquinic acid Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)cc2)[C@@H]1O)C(=O)O BMRSEYFENKXDIS-KLZCAUPSSA-N 0.000 abstract description 22
- 238000000108 ultra-filtration Methods 0.000 abstract description 14
- 241000205585 Aquilegia canadensis Species 0.000 abstract description 10
- 239000010231 banlangen Substances 0.000 abstract description 10
- 238000005516 engineering process Methods 0.000 abstract description 6
- 230000008901 benefit Effects 0.000 abstract description 3
- DGABKXLVXPYZII-UHFFFAOYSA-N Hyodeoxycholic acid Natural products C1C(O)C2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 DGABKXLVXPYZII-UHFFFAOYSA-N 0.000 abstract description 2
- IBFYXTRXDNAPMM-BVTMAQQCSA-N Geniposide Chemical compound O([C@@H]1OC=C([C@@H]2[C@H]1C(=CC2)CO)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O IBFYXTRXDNAPMM-BVTMAQQCSA-N 0.000 abstract 1
- IBFYXTRXDNAPMM-FZEIBHLUSA-N Geniposide Natural products COC(=O)C1=CO[C@@H](O[C@H]2O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]2O)[C@H]2[C@@H]1CC=C2CO IBFYXTRXDNAPMM-FZEIBHLUSA-N 0.000 abstract 1
- VGLLGNISLBPZNL-RBUKDIBWSA-N arborescoside Natural products O=C(OC)C=1[C@@H]2C([C@H](O[C@H]3[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O3)OC=1)=C(CO)CC2 VGLLGNISLBPZNL-RBUKDIBWSA-N 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 142
- 235000019441 ethanol Nutrition 0.000 description 91
- 229940090044 injection Drugs 0.000 description 60
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- 238000005303 weighing Methods 0.000 description 45
- 239000000284 extract Substances 0.000 description 36
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 35
- 238000005057 refrigeration Methods 0.000 description 28
- 238000012546 transfer Methods 0.000 description 27
- XJMPAUZQVRGFRE-SCHFUKFYSA-N Gardenoside Natural products O=C(OC)C=1[C@H]2[C@H]([C@H](O[C@H]3[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O3)OC=1)[C@@](O)(CO)C=C2 XJMPAUZQVRGFRE-SCHFUKFYSA-N 0.000 description 25
- XJMPAUZQVRGFRE-AYDWLWLASA-N methyl (1s,4as,7s,7as)-7-hydroxy-7-(hydroxymethyl)-1-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4a,7a-dihydro-1h-cyclopenta[c]pyran-4-carboxylate Chemical compound O([C@@H]1OC=C([C@@H]2[C@H]1[C@](C=C2)(O)CO)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O XJMPAUZQVRGFRE-AYDWLWLASA-N 0.000 description 25
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 24
- 238000013019 agitation Methods 0.000 description 24
- 238000003756 stirring Methods 0.000 description 23
- 230000006837 decompression Effects 0.000 description 22
- 238000004064 recycling Methods 0.000 description 22
- 238000005406 washing Methods 0.000 description 21
- 235000008504 concentrate Nutrition 0.000 description 19
- 239000012141 concentrate Substances 0.000 description 19
- 238000010438 heat treatment Methods 0.000 description 19
- 239000008155 medical solution Substances 0.000 description 19
- 244000111489 Gardenia augusta Species 0.000 description 17
- 235000018958 Gardenia augusta Nutrition 0.000 description 17
- 238000000967 suction filtration Methods 0.000 description 17
- 241000217407 Margaritifera Species 0.000 description 16
- 239000008215 water for injection Substances 0.000 description 16
- 239000003708 ampul Substances 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 15
- 239000003814 drug Substances 0.000 description 15
- 230000007062 hydrolysis Effects 0.000 description 15
- 238000006460 hydrolysis reaction Methods 0.000 description 15
- 239000000796 flavoring agent Substances 0.000 description 14
- 235000019634 flavors Nutrition 0.000 description 14
- 241000157835 Gardenia Species 0.000 description 13
- 229910021529 ammonia Inorganic materials 0.000 description 12
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- 238000002386 leaching Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 241000334160 Isatis Species 0.000 description 10
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 10
- 239000008363 phosphate buffer Substances 0.000 description 10
- 239000002994 raw material Substances 0.000 description 10
- 235000014347 soups Nutrition 0.000 description 10
- FXNFHKRTJBSTCS-UHFFFAOYSA-N Baicalein Natural products C=1C(=O)C=2C(O)=C(O)C(O)=CC=2OC=1C1=CC=CC=C1 FXNFHKRTJBSTCS-UHFFFAOYSA-N 0.000 description 9
- UDFLTIRFTXWNJO-UHFFFAOYSA-N baicalein Chemical compound O1C2=CC(=O)C(O)=C(O)C2=C(O)C=C1C1=CC=CC=C1 UDFLTIRFTXWNJO-UHFFFAOYSA-N 0.000 description 9
- 229940015301 baicalein Drugs 0.000 description 9
- 238000000605 extraction Methods 0.000 description 9
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
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- 238000002156 mixing Methods 0.000 description 8
- 241000628997 Flos Species 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- -1 filter Substances 0.000 description 6
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 6
- 239000003182 parenteral nutrition solution Substances 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- 239000013049 sediment Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- WBWWGRHZICKQGZ-HZAMXZRMSA-N taurocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 WBWWGRHZICKQGZ-HZAMXZRMSA-N 0.000 description 6
- 238000005199 ultracentrifugation Methods 0.000 description 6
- 102000011759 adducin Human genes 0.000 description 5
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- 229910001422 barium ion Inorganic materials 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- DKPMWHFRUGMUKF-UHFFFAOYSA-N (3alpha,5alpha,6alpha,7alpha)-3,6,7-Trihydroxycholan-24-oic acid Natural products OC1C(O)C2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 DKPMWHFRUGMUKF-UHFFFAOYSA-N 0.000 description 3
- JOYGXTIHTHBSOA-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-thiophen-2-ylprop-2-en-1-one Chemical compound C1=CC(Cl)=CC=C1C(=O)C=CC1=CC=CS1 JOYGXTIHTHBSOA-UHFFFAOYSA-N 0.000 description 3
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 3
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- 229910052925 anhydrite Inorganic materials 0.000 description 3
- XDFCIPNJCBUZJN-UHFFFAOYSA-N barium(2+) Chemical compound [Ba+2] XDFCIPNJCBUZJN-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000000920 calcium hydroxide Substances 0.000 description 3
- 235000011116 calcium hydroxide Nutrition 0.000 description 3
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 3
- 238000005352 clarification Methods 0.000 description 3
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- 238000001035 drying Methods 0.000 description 3
- 125000005909 ethyl alcohol group Chemical group 0.000 description 3
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- 238000009472 formulation Methods 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- 235000014666 liquid concentrate Nutrition 0.000 description 3
- 229910000474 mercury oxide Inorganic materials 0.000 description 3
- LGZXYFMMLRYXLK-UHFFFAOYSA-N mercury(2+);sulfide Chemical compound [S-2].[Hg+2] LGZXYFMMLRYXLK-UHFFFAOYSA-N 0.000 description 3
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
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- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 3
- 235000011149 sulphuric acid Nutrition 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 2
- 229910001863 barium hydroxide Inorganic materials 0.000 description 2
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- 208000030961 allergic reaction Diseases 0.000 description 1
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- 239000007864 aqueous solution Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
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- 229940093181 glucose injection Drugs 0.000 description 1
- 230000002650 habitual effect Effects 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000009112 niuhuang Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
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- 239000001648 tannin Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention discloses a method for preparing the liquid injection or the powder injection for injection of Qingkailing. The method is further improved on the basis of the original preparation process of the liquid injection or the powder injection for injection of Qingkailing. An ultracentrifugal technology is used in the process of preparing the extracting solution of Fructus Gardeniae, Radix Isatidis and honeysuckle, and after the mergence of the extracting solution, the liquid injection or the powder injection for injection of Qingkailing is prepared by using an ultrafiltration technology. The liquid injection or the powder injection for injection of Qingkailing, which is prepared by the method of the present invention, has the advantages of better product stability and longer effective periods. The present invention also discloses a quality control method for baicalin, Cholic acid, Hyodeoxycholic acid, geniposide and chlorogenic acid in the liquid injection or the powder injection for injection of Qingkailing, and also discloses an identification method for the liquid injection or the powder injection for injection of Qingkailing.
Description
This case be No. 03109422.8 the application divide an application the original application applying date: on April 10th, 2003, original application invention and created name: the preparation method of qingkailing injections or injection powder injection and method of quality control thereof.
Technical field
The present invention relates to the preparation method of a kind of qingkailing injections or injection powder injection and the method for quality control of Qingkailing powder injection, specifically, be the improvement preparation method of a kind of qingkailing injections or injection powder injection and the method for quality control and the discrimination method of qingkailing injections or injection powder injection.
Background technology
QINGKAILING ZHUSHEJI is according to traditional Chinese medical theory the Wu of the Qing Dynasty to be brought up in logical " the warm disease bar is debated " " Angong Niuhuang Wan " row side of tearing open analysisization year to come.Being widely used in patients such as high heat, apoplexy clinically, is that numerous medical personnel generally acknowledge and habitual first-aid medicine.The research of relevant Qingkailing preparation aspect just began as far back as the seventies, had formulations such as " qingkailing injections ", " QINGKAILING KOUFUYE ", " QINGKAILING electuary " to come out and be applied to clinical in succession.Yet because injection inconvenience transportation, stability of Oral is poor, and the easy moisture absorption of electuary hardens, its clinical practice of disadvantages affect such as poor stability.In view of above-mentioned many reasons, people have developed freeze drying powder injection on the basis of injection, and Freeze Drying Technique can make medicine keep original physicochemical property and physiologically active, and loss of effective components is few.In addition, the distinctive loose and porous structure of lyophilized formulations can make medicine be easy to again rehydration and recovers active, and the lyophilized formulations water cut is low, easily steady in a long-term the preservation.Thereby both overcome the weak point of oral liquid, electuary, and overcome the shortcoming of injection inconvenience transportation again, and also kept former injection directly to enter body, rapid-action advantage has better curative effect for warm heat disease, acute disease and hyperpyrexia disease disease.Nineteen ninety-five application such as Huang Cheng's steel has also obtained the patent of freeze-dried Qingkailing powder for injection, and this patent is to add excipients sweet mellow wine on the basis of qingkailing injections, aseptic filtration, and freeze drying is made.Preparation technology's patented claim of the Qingkailing powder injection of Changcheng Pharmaceutical Factory, Zhangjiakou application was disclosed on October 1st, 1997, this technology is to be primary raw material with cholic acid 16.25g, hyodesoxycholic acid 18.75g, baicalin 25g, Concha Margaritifera powder 250g, Cornu Bubali powder 125g, cape jasmine 125g Radix Isatidis 1000g, honeysuckle 100g, earlier the preparation Flos Lonicerae extractive solution; Isatis root extract; Gardenia extract; With cholic acid and hyodeoxycholic acid dissolving; Preparation cornu bubali hydrolyzate; Preparation Concha Margaritifera powder hydrolyzate adds the Cornu Bubali powder hydrolyzate with the Concha Margaritifera powder hydrolyzate and prepares cornu bubali and Concha Margaritifera powder mixed liquor; Dissolve baicalin with water for injection; Mix isatis root extract and gardenia extract; Add cholic acid solution again; Add 95% ethanol to containing alcohol amount 70%, refrigerate 24 hours, filter, be concentrated into original volume 1/6-1/7, add Flos Lonicerae extractive solution again, with above-mentioned mixed liquor, cornu bubali and mother-of-pearl mixed liquor and the merging of baicalin aqueous solution obtain total admixing medical solutions, add anhydrous sodium sulfite solution, benefit adds to the full amount of water for injection, and regulates pH to 6.5-7.0, add activated charcoal, water-bath was boiled 1 hour, put the temperature back and filtered, and filtrate refrigeration is placed and spent the night, suction filtration, filtrate water-bath heated and boiled again half an hour, refrigeration is spent the night again, through the miillpore filter suction filtration, obtain the salmon pink soup, freeze drying is made or spray drying is made.Make the Qingkailing powder injection that makes in this way, the term of validity prolongs than liquid drugs injection, is easy to storing, and every index meets the pharmacopeia requirement.
However, we as can be seen the preparation method of above-mentioned Qingkailing powder injection be very loaded down with trivial details, be unfavorable for very much industrialized production, and the quality of Qingkailing powder injection is still waiting further raising.Secondly, the quality control to cholic acid, hyodesoxycholic acid, gardenoside and chlorogenic acid of qingkailing injections or powder ampoule agent for injection is not disclosed in the prior art.
Summary of the invention
For this reason, the present invention proposes the preparation method of a kind of qingkailing injections or powder ampoule agent for injection, this method is more suitable for suitability for industrialized production, and has improved the quality of qingkailing injections or powder ampoule agent for injection greatly.
Simultaneously, the present invention also provides the method for quality control of baicalin, cholic acid, hyodesoxycholic acid, gardenoside and chlorogenic acid in qingkailing injections or the injection powder injection.
The present invention also provides the discrimination method of qingkailing injections or powder ampoule agent for injection.
The inventive method has mainly been used ultracentrifugal technology in the leaching process of cape jasmine, Radix Isatidis and honeysuckle, the impurity in effective like this extract of removing these three kinds of Chinese crude drugs is for later simplification step is got ready.Be specifically
(1) preparation of gardenia extract:
Get cape jasmine, use the poach alcohol deposition method, the filtrate high speed centrifugation makes gardenia extract, and is standby.
(2) preparation of isatis root extract:
Get the Radix Isatidis medicine materical crude slice, use the poach alcohol deposition method, the filtrate high speed centrifugation makes isatis root extract, and is standby.
(3) preparation of Flos Lonicerae extractive solution:
Extracting honeysuckle is used the poach alcohol deposition method, and the filtrate high speed centrifugation makes Flos Lonicerae extractive solution, and is standby.
Centrifugal speed is in the 10000-20000 rev/min of scope in above-mentioned high speed centrifugation, and preferred centrifugal speed is 16000 rev/mins.
In addition, method of the present invention and in preparation cornu bubali and Concha Margaritifera powder potpourri liquid step, added ultrafiltration step.Because cornu bubali contains compositions such as more protein and foreign preteins matter, can stimulate body to produce corresponding antibody, cause allergic reaction, clinical also have a more report.Compositions such as that the application of hyperfiltration technique has been removed effectively is protein-based, tannin have effectively been removed sensibiligen.
Specifically, the preparation of Cornu Bubali powder and Concha Margaritifera powder mixed hydrolysis liquid:
Get the Concha Margaritifera powder hydrolyzate, stir adding Cornu Bubali powder hydrolyzate down, regulate pH value to 4 with barium hydroxide solution, leave standstill, the leaching supernatant checks that barium ion is negative, and regulates pH value to 6～7 with sodium hydroxide solution, filter, filtrate is concentrated into 20 ℃, and to survey relative densities be 1.05 clear cream, puts cold, add ethanol, make to contain the alcohol amount and reach 70%, refrigeration, filter, decompression recycling ethanol is put cold to there not being the alcohol flavor, add ethanol, make to contain alcohol amount and reach 80%, refrigeration filters, decompression recycling ethanol, filter, with the concentrate ultrafiltration, the ultrafiltration liquid cooling is put, filter, promptly get cornu bubali and Concha Margaritifera powder mixed hydrolysis liquid.
Get the Concha Margaritifera powder hydrolyzate, stir adding Cornu Bubali powder hydrolyzate down, regulate pH value to 4 with barium hydroxide solution, leave standstill, the leaching supernatant is checked barium ion with 10% sulfuric acid solution, should be negative, regulate pH value to 6～7 with 10% sodium hydroxide solution, filter, filtrate is concentrated into the clear cream that relative density is 1.05 (20 ℃), puts cold, stir and add 95% ethanol down, make to contain alcohol amount and reach 70%, refrigerate 24 hours, filtration, decompression recycling ethanol is to there not being the alcohol flavor, put coldly, stir and to add ethanol down, make to contain the alcohol amount and reach 80%, refrigerate 24 hours, filter, decompression recycling ethanol filters, with the concentrate ultrafiltration, the ultrafiltration liquid cooling was put 24 hours, filtered, and promptly got cornu bubali and Concha Margaritifera powder mixed hydrolysis liquid.
Just because of adopted above-mentioned steps, make the total mixed liquor of preparation become easy, just, get hyodesoxycholic acid powder, baicalin powder, cholic acid powder respectively in addition the 10% sodium hydroxide solution water for injection of regulating pH value to 8 make dissolving in right amount, mixing; Add in the above-mentioned herbal extract, stir evenly, regulate pH value to 7, get mixed liquor, add to the full amount of water for injection, regulate pH value to 7; With the mixed liquor ultrafiltration, the filtrate freeze drying, promptly.
In the method for the invention, the aseptic filter membrane of 0.2-0.8 μ m, the aseptic filter membrane of preferred 0.22 μ m have been selected in ultrafiltration for use.
The method of quality control of baicalin wraps in the baicalin standard items and adds dissolve with methanol in qingkailing injections of the present invention or the powder ampoule agent for injection, filters, and gets the baicalin reference substance solution, and is standby.High performance liquid chromatograph, with acetonitrile (or methyl alcohol)--(20～45: 80～55) be moving phase, baicalin should be 90.0～110.0% of labelled amount to 0.3～0.6% phosphoric acid (or glacial acetic acid) in mensuration qingkailing injections or the powder ampoule agent for injection.
The method of quality control of cholic acid and hyodesoxycholic acid in qingkailing injections of the present invention or the powder ampoule agent for injection is included in and adds acetonitrile-phosphate buffer system dissolves in the cholic acid standard items, filter, reference substance solution, standby; Use high performance liquid chromatograph, chromatographic column is C18 or C4 or C8 post, and moving phase is with 40～85: 60～15: the methyl alcohol of 0.1～0.5 ratio or acetonitrile-water-glacial acetic acid or phosphatase assay contain cholic acid, hyodesoxycholic acid should be 90.0%～110.0% of labelled amount.
The method of quality control of gardenoside in qingkailing injections of the present invention or the powder ampoule agent for injection is included in and adds methanol-water dissolving in the gardenoside standard items, filter, reference substance solution, standby; Use high performance liquid chromatograph, with 15～40: the methyl alcohol of 85～60 ratios or acetonitrile-water are moving phase, and the product of measuring qingkailing injections or powder ampoule agent for injection contains gardenoside and must not be less than 1.52%.
The method of quality control of chlorogenic acid in qingkailing injections of the present invention or the powder ampoule agent for injection is included in the chlorogenic acid standard items and adds dissolve with methanol, filter, reference substance solution, standby; Use high performance liquid chromatograph, with 8～20: the acetonitrile of 92～80 ratios or methyl alcohol--0.2～0.6% phosphoric acid is moving phase, and the product of measuring qingkailing injections or powder ampoule agent for injection contains chlorogenic acid and must not be less than 0.5%.
The quality standard that qingkailing injections that the inventive method is prepared or powder ampoule agent for injection use the said determination method to measure is that baicalin (C21H18O11) should be 90.0～110.0% of labelled amount; Nitrogenous (N) should be 90.0～120.0% of labelled amount; Contain cholic acid, hyodesoxycholic acid should be 90.0%～110.0% of labelled amount; Contain gardenoside and must not be less than 1.52%, contain chlorogenic acid and must not be less than 0.5%.
The discrimination method of qingkailing injections of the present invention or powder ampoule agent for injection comprises that sample thief adds the alditol solution of 1-10ml new system, with 1-10ml sulfuric acid solution mixing, and the water-bath heating, solution is gray purple; Sample thief adds dissolve with methanol simultaneously, filters, and filtrate concentrates, and gets test liquid; Get the cape jasmine medicinal material, add dissolve with methanol, filter, the residue that filtrate concentrates adds methyl alcohol, gets cape jasmine medicinal material solution; Get the gardenoside standard items and add dissolve with methanol, get the reference substance solution test solution; According to thin-layered chromatography, draw three kinds of solution, put in the pre-plate-making of GF254, with ethyl acetate-absolute ethyl alcohol-glacial acetic acid expansion of 8-12: 1-3: 0.5-1.5, spray is pressed from both sides blue aldehyde-concentrated sulfuric acid solution with perfume (or spice), in the test sample chromatogram with reference substance chromatogram relevant position on show the same color spot arranged.
Use prepared qingkailing injections of the inventive method or injection powder injection, good stability, the term of validity is long, and transportation is stored convenient, and every technical indicator meets Pharmacopoeia of the People's Republic of China requirement.The using method of qingkailing injections of the present invention or injection powder injection is intramuscular injection: one 2～4ml.Patient with severe symptoms's intravenous injection 20～40ml uses with 10% glucose injection 200ml or physiological saline 100ml dilution back.
Embodiment
Embodiment 1:
Cholic acid 32.5g hyodesoxycholic acid 37.5g baicalin 50g Concha Margaritifera powder 500g
Cornu Bubali powder 250g cape jasmine 250g Radix Isatidis 2000g Honegsukle flower P.E 50g
The detailed process step of preparation powder-injection is poly-as follows:
1, the extraction of medicine and hydrolysis process:
1. the preparation of gardenia extract: take by weighing cape jasmine by recipe quantity, add 6 times of water gagings and boiled 1 hour, filter, filter residue adds 4 times of water gagings again, boil and carry half an hour, filter, filtrate merges, and heating is concentrated into the suitable volume of raw material weight, put and under agitation add dense ethanol after cold, make and contain alcohol amount and reach 60%, refrigeration 2～3 little days, suction filtration, get clear filtrate, precipitation merges washing lotion and filtrate, decompression recycling ethanol with 60% cold ethanol washing, 10000 rev/mins of ultracentrifugations, refrigerate after 24 hours, filter to such an extent that clarify gardenia extract, refrigeration is placed for dosing and is used;
2. the preparation of isatis root extract: take by weighing the Radix Isatidis medicine materical crude slice by recipe quantity, add 6～7 times of water gagings, boiled 1 hour, filter, filter residue adds 4～5 times of water gagings again, boils half an hour, and the leaching extract discards the dregs of a decoction; When merging filtrate, heating make soup be concentrated into the suitable volume of raw material weight, put coldly, under agitation add dense ethanol, reach 60%, refrigerate 2～3 days, filter to containing the alcohol amount, decompression filtrate recycling ethanol, concentrate refrigeration was placed 24 hours, and filtration must be clarified concentrate;
Get concentrate dropping ammonia under agitation, fully stir, make the pH value transfer to 8.5～9.0, refrigeration was placed 24 hours, it is diffusing not allow ammonia wave, and with paper pulp cake suction filtration, filtrate is heated in water-bath, removes ammonia to ammonia flavor and disappear under constantly stirring, to pH to 5.5～6.0 o'clock, refrigeration is placed, and uses for dosing;
3. the extraction of Honegsukle flower P.E: take by weighing honeysuckle and put to boil and carry in the pot, add 15 times of water, little boil to boil carry 1 hour, filter, the dregs of a decoction add 10 times of water gagings, boil and carry half an hour, filter, and discard the dregs of a decoction; Merge filtrate twice, heating is concentrated into 1/8 of original volume～1/9 o'clock, and taking out with 20% milk of lime adjusting pH is 12, the leaching sediment;
Taking precipitate under agitation adds 2～3 times of amounts of sediment, 95% ethanol in container, transfer pH=3～4 with 50% sulfuric acid, after fully stirring, filter, filtrate neutralizes with 40% NaOH, transfers pH=6.5～7, filter, filtrate recycling ethanol, 10000 rev/mins of ultracentrifugations are concentrated into the thick paste shape again, put 80 ℃ of oven dry in the drying box, get brown extract; Put in the exsiccator preserve standby;
4. take by weighing Cornu Bubali powder by recipe quantity, put in the beaker, add 8 times of amount 4N NaOH Ba (OH) 2 hot solution, be heated to and boil, constantly stir, be hydrolyzed 6～8 hours, treat that Cornu Bubali powder all is hydrolyzed into till the no brown particle; When putting temperature to 40～50 ℃, incline and get supernatant, filter, filter residue is collected all solution with small amount of thermal washing 1～2 time, places standby;
5. press recipe quantity, take by weighing Concha Margaritifera powder, put in the flask, add 6～8 times of amount 4N sulfuric acid solutions, be heated to and boil, hydrolysis 6～8 hours, treat that Nacre transfers yellow mercury oxide (CaSO4 ↓) to by grey, stop heating, put temperature to 40～50 ℃, filter, filter residue merges with small amount of thermal water washing 3 times, washing lotion and filtrate, puts cold back adularescent acicular crystal and separates out, refilter and remove, get light yellow transparent solution;
Barium sulphate impurity such as (BaSO4) is removed in neutralization: water intaking horn powder hydrolyzate, under agitation join in the mother-of-pearl hydrolyzate, and after all the cornu bubali hydrolyzate adds,, add an amount of Ba (OH) 2 solids again as the mixed liquor peracid, the stirring and dissolving adjust pH is 4; Placement is sunk precipitation, ultrafiltration 10000 molecular weight, and leaching mixes hydrolyzate, wherein uses 10%H2SO4 fluid inspection Ba2+, should be negative, and transfers Ph=6～7 with 10%NaOH liquid again, and suction filtration gets faint yellow clarified solution;
Mixed hydrolysis liquid concentrates with pure and handles: the mixed hydrolysis liquid of clarification is put in the evaporating dish, and heating evaporation concentrates, and during to 2～3 times of amounts of suitable raw material total amount, puts cold; Under agitation add dense ethanol, make to contain alcohol amount and reach 60%, refrigerate 24 hours, filter, decompression recycling ethanol does not only have the alcohol flavor near; Emitting refrigeration uses for dosing;
2, the preparation of parenteral solution:
(1) mixing of extraction soup: water intaking ox horn and mother-of-pearl mixed extract under agitation add isatis root extract; Add gardenia extract again; Mix, regulate pH6～7, suction filtration gets clear and bright orange-red solution A;
(2) dissolving of cholaic acid and hyocholic acid: it is an amount of to take 95% saturated ethanol of solid NaOH, stirs to be sprinkled into the cholaic acid fine powder down gradually, transfers pH8.5～9.0, makes its whole dissolvings; Merge two sodium taurocholate solution, join in the A liquid;
(3) alcohol of admixing medical solutions is handled: admixing medical solutions such as water intaking ox horn, and add 95% ethanol and make and contain the alcohol amount and reach 70%, regulate pH6.5～7.0, refrigerate 24 hours, filter, decompression filtrate recycling ethanol is distinguished the flavor of to there not being alcohol;
(4) baicalein and Honegsukle flower P.E are handled and dissolving:
Get an amount of water for injection, transfer about pH to 8, under agitation be sprinkled into the baicalein fine powder with 10%NaOH, make whole dissolvings after, transfer about pH to 7;
The extracting honeysuckle extract adds a small amount of water for injection, transfers with 95% ethanol to contain the alcohol amount and reach 80%, refrigerate 24 hours, suction filtration, precipitation merges washing lotion and filtrate with the washing of 80% ethanol, decompression recycling ethanol is not to there being the alcohol flavor, continuation concentrated golden yellow thick paste;
With the refining Flos Lonicerae extractive solution of solution dissolving that contains baicalein, incorporate in the admixing medical solutions, get total admixing medical solutions;
(5) processing of total admixing medical solutions: measure admixing medical solutions, add water for injection, regulate pH6.5～7.0 to 2000ml, add 0.2% activated charcoal, water-bath was boiled 1 hour, put the temperature back and filtered, and filtrate refrigeration is placed and spent the night, filter, filtrate is heated half an hour with boiling water bath, and refrigeration is spent the night again, with 0.2 μ m filter membrane ultrafiltration, get clear and bright Chinese red soup, the pH value should be 6.5～7.0; Be distributed into 2000 bottles, every bottle of 1ml, suitable crude drug 1.6g, freeze drying is promptly.
Embodiment 2:
Cholic acid 32.5g hyodesoxycholic acid 37.5g baicalin 50g Concha Margaritifera powder 500g
Cornu Bubali powder 250g cape jasmine 250g Radix Isatidis 2000g Honegsukle flower P.E 50g
The detailed process step of preparation parenteral solution is poly-as follows:
1, the extraction of medicine and hydrolysis process:
1. the preparation of gardenia extract: take by weighing cape jasmine by recipe quantity, add 6 times of water gagings and boiled 1 hour, filter, filter residue adds 4 times of water gagings again, boil and carry half an hour, filter, filtrate merges, and heating is concentrated into the suitable volume of raw material weight, put and under agitation add dense ethanol after cold, make and contain alcohol amount and reach 60%, refrigeration 2～3 little days, suction filtration, get clear filtrate, precipitation merges washing lotion and filtrate, decompression recycling ethanol with 60% cold ethanol washing, 12000 rev/mins of ultracentrifugations, refrigerate after 24 hours, filter to such an extent that clarify gardenia extract, refrigeration is placed for dosing and is used;
2. the preparation of isatis root extract: take by weighing the Radix Isatidis medicine materical crude slice by recipe quantity, add 6～7 times of water gagings, boiled 1 hour, filter, filter residue adds 4～5 times of water gagings again, boils half an hour, and the leaching extract discards the dregs of a decoction; When merging filtrate, heating make soup be concentrated into the suitable volume of raw material weight, put coldly, under agitation add dense ethanol, reach 60%, refrigerate 2～3 days, filter to containing the alcohol amount, decompression filtrate recycling ethanol, concentrate refrigeration was placed 24 hours, and filtration must be clarified concentrate;
Get concentrate dropping ammonia under agitation, fully stir, make the pH value transfer to 8.5～9.0, refrigeration was placed 24 hours, it is diffusing not allow ammonia wave, and with paper pulp cake suction filtration, filtrate is heated in water-bath, removes ammonia to ammonia flavor and disappear under constantly stirring, to pH to 5.5～6.0 o'clock, refrigeration is placed, and uses for dosing;
3. the extraction of Honegsukle flower P.E: take by weighing honeysuckle and put to boil and carry in the pot, add 15 times of water, little boil to boil carry 1 hour, filter, the dregs of a decoction add 10 times of water gagings, boil and carry half an hour, filter, and discard the dregs of a decoction; Merge filtrate twice, heating is concentrated into 1/8 of original volume～1/9 o'clock, and taking out with 20% milk of lime adjusting pH is 12, the leaching sediment;
Taking precipitate under agitation adds 2～3 times of amounts of sediment, 95% ethanol in container, transfer pH=3～4 with 50% sulfuric acid, after fully stirring, filter, filtrate neutralizes with 40% NaOH, transfers pH=6.5～7, filter, filtrate recycling ethanol, 12000 rev/mins of ultracentrifugations are concentrated into the thick paste shape again, put 80 ℃ of oven dry in the drying box, get brown extract; Put in the exsiccator preserve standby;
4. take by weighing Cornu Bubali powder by recipe quantity, put in the beaker, add 8 times of amount 4N NaOH Ba (OH) 2 hot solution, be heated to and boil, constantly stir, be hydrolyzed 6～8 hours, treat that Cornu Bubali powder all is hydrolyzed into till the no brown particle; When putting temperature to 40～50 ℃, incline and get supernatant, filter, filter residue is collected all solution with small amount of thermal washing 1～2 time, places standby;
5. press recipe quantity, take by weighing Concha Margaritifera powder, put in the flask, add 6～8 times of amount 4N sulfuric acid solutions, be heated to and boil, hydrolysis 6～8 hours, treat that Nacre transfers yellow mercury oxide (CaSO4 ↓) to by grey, stop heating, put temperature to 40～50 ℃, filter, filter residue merges with small amount of thermal water washing 3 times, washing lotion and filtrate, puts cold back adularescent acicular crystal and separates out, refilter and remove, get light yellow transparent solution;
Barium sulphate impurity such as (BaSO4) is removed in neutralization: water intaking horn powder hydrolyzate, under agitation join in the mother-of-pearl hydrolyzate, and after all the cornu bubali hydrolyzate adds,, add an amount of Ba (OH) 2 solids again as the mixed liquor peracid, the stirring and dissolving adjust pH is 4; Placement is sunk precipitation, ultrafiltration 10000 molecular weight, and leaching mixes hydrolyzate, wherein uses 10%H2SO4 fluid inspection Ba2+, should be negative, and transfers Ph=6～7 with 10%NaOH liquid again, and suction filtration gets faint yellow clarified solution;
Mixed hydrolysis liquid concentrates with pure and handles: the mixed hydrolysis liquid of clarification is put in the evaporating dish, and heating evaporation concentrates, and during to 2～3 times of amounts of suitable raw material total amount, puts cold; Under agitation add dense ethanol, make to contain alcohol amount and reach 60%, refrigerate 24 hours, filter, decompression recycling ethanol does not only have the alcohol flavor near; Emitting refrigeration uses for dosing;
2, the preparation of parenteral solution:
(1) mixing of extraction soup: water intaking ox horn and mother-of-pearl mixed extract under agitation add isatis root extract; Add gardenia extract again; Mix, regulate pH6～7, suction filtration gets clear and bright orange-red solution A;
(2) dissolving of cholaic acid and hyocholic acid: it is an amount of to take 95% saturated ethanol of solid NaOH, stirs to be sprinkled into the cholaic acid fine powder down gradually, transfers pH8.5～9.0, makes its whole dissolvings; Merge two sodium taurocholate solution, join in the A liquid;
(3) alcohol of admixing medical solutions is handled: admixing medical solutions such as water intaking ox horn, and add 95% ethanol and make and contain the alcohol amount and reach 70%, regulate pH6.5～7.0, refrigerate 24 hours, filter, decompression filtrate recycling ethanol is distinguished the flavor of to there not being alcohol;
(4) baicalein and Honegsukle flower P.E are handled and dissolving:
Get an amount of water for injection, transfer about pH to 8, under agitation be sprinkled into the baicalein fine powder with 10%NaOH, make whole dissolvings after, transfer about pH to 7;
The extracting honeysuckle extract adds a small amount of water for injection, transfers with 95% ethanol to contain the alcohol amount and reach 80%, refrigerate 24 hours, suction filtration, precipitation merges washing lotion and filtrate with the washing of 80% ethanol, decompression recycling ethanol is not to there being the alcohol flavor, continuation concentrated golden yellow thick paste;
With the refining Flos Lonicerae extractive solution of solution dissolving that contains baicalein, incorporate in the admixing medical solutions, get total admixing medical solutions;
(5) processing of total admixing medical solutions: measure admixing medical solutions, add water for injection, regulate pH6.5～7.0 to 2000ml, add 0.2% activated charcoal, water-bath was boiled 1 hour, put the temperature back and filtered, and filtrate refrigeration is placed and spent the night, filter, filtrate is heated half an hour with boiling water bath, and refrigeration is spent the night again, with 0.5 μ m filter membrane ultrafiltration, get clear and bright Chinese red soup, the pH value should be 6.5～7.0; Be distributed into 2000 bottles, every bottle of 1ml, quite crude drug 1.6g is promptly.
Embodiment 3:
Cholic acid 32.5g hyodesoxycholic acid 37.5g baicalin 50g Concha Margaritifera powder 500g
Cornu Bubali powder 250g cape jasmine 250g Radix Isatidis 2000g Honegsukle flower P.E 50g
The detailed process step of preparation freeze drying powder injection is poly-as follows:
1, the extraction of medicine and hydrolysis process:
1. the preparation of gardenia extract: take by weighing cape jasmine by recipe quantity, add 6 times of water gagings and boiled 1 hour, filter, filter residue adds 4 times of water gagings again, boil and carry half an hour, filter, filtrate merges, and heating is concentrated into the suitable volume of raw material weight, put and under agitation add dense ethanol after cold, make and contain alcohol amount and reach 60%, refrigeration 2～3 little days, suction filtration, get clear filtrate, precipitation merges washing lotion and filtrate, decompression recycling ethanol with 60% cold ethanol washing, 16000 rev/mins of ultracentrifugations, refrigerate after 24 hours, filter to such an extent that clarify gardenia extract, refrigeration is placed for dosing and is used;
2. the preparation of isatis root extract: take by weighing the Radix Isatidis medicine materical crude slice by recipe quantity, add 6～7 times of water gagings, boiled 1 hour, filter, filter residue adds 4～5 times of water gagings again, boils half an hour, and the leaching extract discards the dregs of a decoction; When merging filtrate, heating make soup be concentrated into the suitable volume of raw material weight, put coldly, under agitation add dense ethanol, reach 60%, refrigerate 2～3 days, filter to containing the alcohol amount, decompression filtrate recycling ethanol, concentrate refrigeration was placed 24 hours, and filtration must be clarified concentrate;
Get concentrate dropping ammonia under agitation, fully stir, make the pH value transfer to 8.5～9.0, refrigeration was placed 24 hours, it is diffusing not allow ammonia wave, and with paper pulp cake suction filtration, filtrate is heated in water-bath, removes ammonia to ammonia flavor and disappear under constantly stirring, to pH to 5.5～6.0 o'clock, refrigeration is placed, and uses for dosing;
3. the extraction of Honegsukle flower P.E: take by weighing honeysuckle and put to boil and carry in the pot, add 15 times of water, little boil to boil carry 1 hour, filter, the dregs of a decoction add 10 times of water gagings, boil and carry half an hour, filter, and discard the dregs of a decoction; Merge filtrate twice, heating is concentrated into 1/8 of original volume～1/9 o'clock, and taking out with 20% milk of lime adjusting pH is 12, the leaching sediment;
Taking precipitate under agitation adds 2～3 times of amounts of sediment, 95% ethanol in container, transfer pH=3～4 with 50% sulfuric acid, after fully stirring, filter, filtrate neutralizes with 40% NaOH, transfers pH=6.5～7, filter, filtrate recycling ethanol, 16000 rev/mins of ultracentrifugations are concentrated into the thick paste shape again, put 80 ℃ of oven dry in the drying box, get brown extract; Put in the exsiccator preserve standby;
4. take by weighing Cornu Bubali powder by recipe quantity, put in the beaker, add 8 times of amount 4N NaOH Ba (OH) 2 hot solution, be heated to and boil, constantly stir, be hydrolyzed 6～8 hours, treat that Cornu Bubali powder all is hydrolyzed into till the no brown particle; When putting temperature to 40～50 ℃, incline and get supernatant, filter, filter residue is collected all solution with small amount of thermal washing 1～2 time, places standby;
5. press recipe quantity, take by weighing Concha Margaritifera powder, put in the flask, add 6～8 times of amount 4N sulfuric acid solutions, be heated to and boil, hydrolysis 6～8 hours, treat that Nacre transfers yellow mercury oxide (CaSO4 ↓) to by grey, stop heating, put temperature to 40～50 ℃, filter, filter residue merges with small amount of thermal water washing 3 times, washing lotion and filtrate, puts cold back adularescent acicular crystal and separates out, refilter and remove, get light yellow transparent solution;
Barium sulphate impurity such as (BaSO4) is removed in neutralization: water intaking horn powder hydrolyzate, under agitation join in the mother-of-pearl hydrolyzate, and after all the cornu bubali hydrolyzate adds,, add an amount of Ba (OH) 2 solids again as the mixed liquor peracid, the stirring and dissolving adjust pH is 4; Placement is sunk precipitation, ultrafiltration 10000 molecular weight, and leaching mixes hydrolyzate, wherein uses 10%H2SO4 fluid inspection Ba2+, should be negative, and transfers Ph=6～7 with 10%NaOH liquid again, and suction filtration gets faint yellow clarified solution;
Mixed hydrolysis liquid concentrates with pure and handles: the mixed hydrolysis liquid of clarification is put in the evaporating dish, and heating evaporation concentrates, and during to 2～3 times of amounts of suitable raw material total amount, puts cold; Under agitation add dense ethanol, make to contain alcohol amount and reach 60%, refrigerate 24 hours, filter, decompression recycling ethanol does not only have the alcohol flavor near; Emitting refrigeration uses for dosing;
2, the preparation of parenteral solution:
(1) mixing of extraction soup: water intaking ox horn and extra large pearl oyster mixed extract under agitation add isatis root extract; Add gardenia extract again; Mix, regulate pH6～7, suction filtration gets clear and bright orange-red solution A;
(2) dissolving of cholaic acid and hyocholic acid: it is an amount of to take 95% saturated ethanol of solid NaOH, stirs to be sprinkled into the cholaic acid fine powder down gradually, transfers pH8.5～9.0, makes its whole dissolvings; Merge two sodium taurocholate solution, join in the A liquid;
(3) alcohol of admixing medical solutions is handled: admixing medical solutions such as water intaking ox horn, and add 95% ethanol and make and contain the alcohol amount and reach 70%, regulate pH6.5～7.0, refrigerate 24 hours, filter, decompression filtrate recycling ethanol is distinguished the flavor of to there not being alcohol;
(4) baicalein and Honegsukle flower P.E are handled and dissolving:
Get an amount of water for injection, transfer about pH to 8, under agitation be sprinkled into the baicalein fine powder with 10%NaOH, make whole dissolvings after, transfer about pH to 7;
The extracting honeysuckle extract adds a small amount of water for injection, transfers with 95% ethanol to contain the alcohol amount and reach 80%, refrigerate 24 hours, suction filtration, precipitation merges washing lotion and filtrate with the washing of 80% ethanol, decompression recycling ethanol is not to there being the alcohol flavor, continuation concentrated golden yellow thick paste;
With the refining Flos Lonicerae extractive solution of solution dissolving that contains baicalein, incorporate in the admixing medical solutions, get total admixing medical solutions;
(5) processing of total admixing medical solutions: measure admixing medical solutions, add water for injection, regulate pH6.5～7.0 to 2000ml, add 0.2% activated charcoal, water-bath was boiled 1 hour, put the temperature back and filtered, and filtrate refrigeration is placed and spent the night, filter, filtrate is heated half an hour with boiling water bath, and refrigeration is spent the night again, with 0.8 μ m filter membrane ultrafiltration, get clear and bright Chinese red soup, the pH value should be 6.5～7.0; Be distributed into 2000 bottles, every bottle of 1ml, suitable crude drug 1.6g, freeze drying is promptly.
Embodiment 4: the method for quality control of qingkailing injections or powder ampoule agent for injection
Differentiate:
A. get 1 bottle of this product and add 5ml water for injection dissolving, (heating is 10 minutes in 70 ℃ of water-baths for 1 → 10ml) 1ml, sulfuric acid solution (get sulfuric acid 50ml, add water 65ml and mix) 10ml, mixing, and solution shows gray purple to get the furfural solution that 0.5ml adds new preparation.
B. get this product and add the 5ml dissolve with methanol for 1 bottle, filter, filtrate decompression is concentrated into 1ml, as need testing solution; Take by weighing cape jasmine medicinal material 0.5g, add methyl alcohol 10ml lixiviate and spend the night, filter, the residue after filtrate concentrates adds that methyl alcohol is molten to get cape jasmine medicinal material solution to 2ml; Taking by weighing gardenoside standard items 2mg again, to add methyl alcohol molten to 1ml product solution in contrast.Test according to thin-layered chromatography (an appendix VI of Chinese Pharmacopoeia B), draw each 5 μ l of above-mentioned three kinds of solution, put respectively on same silica GF254 prefabricated board, launch with ethyl acetate-absolute ethyl alcohols of 10: 2: 1-glacial acetic acid, dry, spray is with the blue aldehyde-concentrated sulfuric acid solution of 1% fragrant folder, 105 ℃ of bakings 5 minutes, in the test sample chromatogram with the corresponding position of reference substance chromatogram on show the same color spot arranged.
Assay:
A. baicalin:
Get Qingkailing powder injection sample 3mg, the accurate title, decide, and puts in the 5ml volumetric flask, and it is molten to scale to add methyl alcohol, and the aperture is 0.45 μ m filtering with microporous membrane, gets subsequent filtrate as test solution; Other gets the baicalin standard items, and accurate the title decides, and adds dissolve with methanol and makes the solution that every 1ml contains 50 μ g, in contrast product solution.Measure according to high performance liquid chromatography (" an appendix VI of Chinese pharmacopoeia nineteen ninety-five version D), accurate respectively baicalin reference substance solution and each 10 μ l of need testing solution of drawing, inject high performance liquid chromatograph, moving phase was with 28: 72 acetonitrile-0.025M phosphoric acid, the detection wavelength is 276nm, measure the peak area integrated value, calculate promptly with external standard method.This product contains baicalin (C21H18O11) and should be 90.0～110.0% of labelled amount.
B. cholic acid, hyodesoxycholic acid:
The reference substance solution preparation: precision takes by weighing cholic acid standard items 2mg, puts in the 2ml volumetric flask, and it is molten to scale to add 35: 65 acetonitrile-0.025M phosphate buffer pH3.0; Precision takes by weighing hyodesoxycholic acid standard items 2mg, puts in the 2ml volumetric flask, and it is molten to scale to add 35: 65 acetonitrile-0.025M phosphate buffer pH 3.0.The test liquid preparation: precision takes by weighing Qingkailing powder injection sample 20mg and puts in the 2ml volumetric flask, and it is molten to scale to add 35: 65 acetonitrile-0.025M phosphate buffer pH3.0, and filtering with microporous membrane gets test liquid." an appendix VI of Chinese pharmacopoeia D measures according to high performance liquid chromatography, accurate respectively each the 10 μ l of cholic acid, hyodesoxycholic acid reference substance solution and test liquid that draw, inject high performance liquid chromatograph, chromatographic column C18ODS post, moving phase is with 35: 65 acetonitrile-0.025M phosphate pH3.0, flow velocity 1.0ml/min, and the detection wavelength is 205nm, measure cholic acid, hyodesoxycholic acid peak area integrated value, calculate with external standard method.This product contains cholic acid, hyodesoxycholic acid should be 90.0%～110.0% of labelled amount.
C. gardenoside:
The reference substance solution preparation, precision takes by weighing gardenoside standard items 1mg, puts in the 2ml volumetric flask, and it is molten to scale to add 30: 70 methanol-waters; The test liquid preparation: precision takes by weighing Qingkailing powder injection sample 5mg and puts in the 2ml volumetric flask, and it is molten to scale to add 30: 70 methanol-waters, and filtering with microporous membrane gets test liquid." an appendix VI of Chinese pharmacopoeia D measures according to high performance liquid chromatography, accurate respectively gardenoside reference substance solution and each 10 μ l of test liquid of drawing, inject high performance liquid chromatograph, chromatographic column C18ODS post, moving phase is with 30: 70 methanol-waters, flow velocity 1.0ml/min, and the detection wavelength is 237nm, measure gardenoside peak area integrated value, calculate with external standard method; This product contains gardenoside must not be less than 1.52%.
D. chlorogenic acid:
The reference substance solution preparation, precision takes by weighing chlorogenic acid 1mg and puts in the 10ml volumetric flask, and it is molten to scale to add methyl alcohol; The test liquid preparation: precision takes by weighing sample 20mg, puts in the 2ml volumetric flask, and it is molten to scale to add methyl alcohol, and filtering with microporous membrane gets test liquid." an appendix VI of Chinese pharmacopoeia D measures according to high performance liquid chromatography, accurate respectively chlorogenic acid reference substance solution and each 10 μ l of test liquid of drawing, inject high performance liquid chromatograph, chromatographic column C18ODS post, moving phase is with 10: 90 acetonitrile-0.025M phosphate, flow velocity 1.0ml/min, and the detection wavelength is 326nm, measure chlorogenic acid peak area integrated value, calculate with external standard method.This product contains chlorogenic acid must not be less than 0.5%.
E. nitrogen content:
Precision takes by weighing this product 2mg, the photograph n2 method (" an appendix IX of Chinese pharmacopoeia nineteen ninety-five version L second method) measure, that is, this product nitrogenous (N) should be 90.0～120.0% of labelled amount.
Embodiment 5: the discrimination method of parenteral solution of the present invention or injection powder injection
Differentiate:
A. get 1 bottle of Qingkailing powder injection and add dissolving of 5ml water for injection or qingkailing injections 5ml, get furfural solution (1 → 10ml) 1ml, sulfuric acid solution (get sulfuric acid 50ml, add water 65ml and mix) 10ml, mixing that 0.5ml adds new preparation, heating is 10 minutes in 70 ℃ of water-baths, and solution shows gray purple.
B. get Qingkailing powder injection and add the 5ml dissolve with methanol for 1 bottle, filter, filtrate decompression is concentrated into 1ml, as need testing solution; Take by weighing cape jasmine medicinal material 0.5g, add methyl alcohol 10ml lixiviate and spend the night, filter, the residue after filtrate concentrates adds that methyl alcohol is molten to get cape jasmine medicinal material solution to 2ml; Taking by weighing gardenoside 2mg again, to add methyl alcohol molten to 1ml product solution in contrast.Test according to thin-layered chromatography (an appendix VI of Chinese Pharmacopoeia B), draw each 5 μ l of above-mentioned three kinds of solution, put respectively on same silica GF254 prefabricated board, launch with ethyl acetate-absolute ethyl alcohols of 10: 2: 1-glacial acetic acid, dry, spray is with the blue aldehyde-concentrated sulfuric acid solution of 1% fragrant folder, 105 ℃ of bakings 5 minutes, in the test sample chromatogram with the corresponding position of reference substance chromatogram on show the same color spot arranged.
Assay:
A. baicalin:
Get about Qingkailing powder injection 3mg, the accurate title, decide, and puts in the 5ml volumetric flask, and it is molten to scale to add methyl alcohol, and the aperture is 0.45 μ m filtering with microporous membrane, gets subsequent filtrate as test solution; Other gets the baicalin reference substance, and accurate the title decides, and adds dissolve with methanol and makes the solution that every 1ml contains 50 μ g, in contrast product solution.Measure according to high performance liquid chromatography (" an appendix VI of Chinese pharmacopoeia nineteen ninety-five version D), accurate respectively baicalin reference substance solution and each 10 μ l of need testing solution of drawing, inject high performance liquid chromatograph, moving phase was with 30: 70 acetonitrile-0.025M phosphoric acid, the detection wavelength is 276nm, measure the peak area integrated value, calculate promptly with external standard method.This product contains baicalin (C21H18O11) and should be 90.0～110.0% of labelled amount.
B. cholic acid, hyodesoxycholic acid:
The reference substance solution preparation, precision takes by weighing cholic acid 2mg, puts in the 2ml volumetric flask, and it is molten to scale to add 35: 65 acetonitrile-0.025M phosphate buffer pH3.0; Precision takes by weighing hyodesoxycholic acid 2mg, puts in the 2ml volumetric flask, and it is molten to scale to add 35: 65 acetonitrile-0.025M phosphate buffer pH3.0.The test liquid preparation: precision takes by weighing this product 20mg and puts in the 2ml volumetric flask, and it is molten to scale to add 35: 65 acetonitrile-0.025M phosphate buffer pH3.0, and filtering with microporous membrane gets test liquid." an appendix VI of Chinese pharmacopoeia D measures according to high performance liquid chromatography, accurate respectively each the 10 μ l of cholic acid, hyodesoxycholic acid reference substance solution and test liquid that draw, inject high performance liquid chromatograph, chromatographic column C18ODS post, moving phase is with 38: 62 acetonitrile-0.025M phosphate pH3.0, flow velocity 1.0ml/min, and the detection wavelength is 205nm, measure cholic acid, hyodesoxycholic acid peak area integrated value, calculate with external standard method.This product contains cholic acid, hyodesoxycholic acid should be 90.0%～110.0% of labelled amount.
C. gardenoside:
The reference substance solution preparation, precision takes by weighing gardenoside standard items 1mg, puts in the 2ml volumetric flask, and it is molten to scale to add 30: 70 methanol-waters.The test liquid preparation: precision takes by weighing Qingkailing powder injection 5mg and puts in the 2ml volumetric flask, and it is molten to scale to add 30: 70 methanol-waters, and filtering with microporous membrane gets test liquid." an appendix VI of Chinese pharmacopoeia D measures according to high performance liquid chromatography, accurate respectively gardenoside reference substance solution and each 10 μ l of test liquid of drawing, inject high performance liquid chromatograph, chromatographic column C18ODS post, moving phase is with 35: 65 methanol-waters, flow velocity 1.0ml/min, and the detection wavelength is 237nm, measure gardenoside peak area integrated value, calculate with external standard method.This product contains gardenoside must not be less than 1.52%.
D. chlorogenic acid:
The reference substance solution preparation, precision takes by weighing chlorogenic acid standard items 1mg and puts in the 10ml volumetric flask, and it is molten to scale to add methyl alcohol.The test liquid preparation: precision takes by weighing Qingkailing powder injection sample 20mg, puts in the 2ml volumetric flask, and it is molten to scale to add methyl alcohol, and filtering with microporous membrane gets test liquid." an appendix VI of Chinese pharmacopoeia D measures according to high performance liquid chromatography, accurate respectively chlorogenic acid reference substance solution and each 10 μ l of test liquid of drawing, inject high performance liquid chromatograph, chromatographic column C18ODS post, moving phase is with 15: 85 acetonitrile-0.025M phosphate, flow velocity 1.0ml/min, and the detection wavelength is 326nm, measure chlorogenic acid peak area integrated value, calculate with external standard method.This product contains chlorogenic acid must not be less than 0.5%.
E. nitrogen content:
Precision takes by weighing Qingkailing powder injection sample 2mg, the photograph n2 method (" an appendix IX of Chinese pharmacopoeia nineteen ninety-five version L second method) measure, that is, this product nitrogenous (N) should be 90.0～120.0% of labelled amount.
Embodiment 6: the method for quality control of parenteral solution of the present invention or powder ampoule agent for injection
Differentiate: a. gets 1 bottle of Qingkailing powder injection and adds the dissolving of 5ml water for injection or get qingkailing injections 5ml, (1 → 10ml) 1ml, sulfuric acid solution (are got sulfuric acid 50ml to get the furfural solution that 0.5ml adds new preparation, adding water 65ml mixes) 10ml, mixing, heating is 10 minutes in 70 ℃ of water-baths, and solution shows gray purple.
B. get this product and add the 5ml dissolve with methanol for 1 bottle, filter, filtrate decompression is concentrated into 1ml, as need testing solution, takes by weighing cape jasmine medicinal material 0.5g, adds methyl alcohol 10ml lixiviate and spends the night, and filters, and the residue after filtrate concentrates adds that methyl alcohol is molten to get cape jasmine medicinal material solution to 2ml; Taking by weighing gardenoside standard items 2mg again, to add methyl alcohol molten to 1ml product solution in contrast.Test according to thin-layered chromatography (an appendix VI of Chinese Pharmacopoeia B), draw each 5 μ l of above-mentioned three kinds of solution, put respectively on same silica GF254 prefabricated board, launch with ethyl acetate-absolute ethyl alcohols of 10: 2: 1-glacial acetic acid, dry, spray is with the blue aldehyde-concentrated sulfuric acid solution of 1% fragrant folder, 105 ℃ of bakings 5 minutes, in the test sample chromatogram with the corresponding position of reference substance chromatogram on show the same color spot arranged.
Assay:
A. baicalin:
Get Qingkailing powder injection sample 3mg, the accurate title, decide, and puts in the 5ml volumetric flask, and it is molten to scale to add methyl alcohol, and the aperture is 0.45 μ m filtering with microporous membrane, gets subsequent filtrate as test solution; Other gets the baicalin reference substance, and accurate the title decides, and adds dissolve with methanol and makes the solution that every 1ml contains 50 μ g, in contrast product solution.Measure according to high performance liquid chromatography (" an appendix VI of Chinese pharmacopoeia nineteen ninety-five version D), accurate respectively baicalin reference substance solution and each 10 μ l of need testing solution of drawing, inject high performance liquid chromatograph, moving phase was with 40: 60 acetonitrile-0.025M phosphoric acid, the detection wavelength is 276nm, measure the peak area integrated value, calculate promptly with external standard method.This product contains baicalin (C21H18O11) and should be 90.0～110.0% of labelled amount.
B. cholic acid, hyodesoxycholic acid:
The reference substance solution preparation, precision takes by weighing cholic acid standard items 2mg, puts in the 2ml volumetric flask, and it is molten to scale to add 35: 65 acetonitrile-0.025M phosphate buffer pH3.0; Precision takes by weighing hyodesoxycholic acid standard items 2mg, puts in the 2ml volumetric flask, and it is molten to scale to add 35: 65 acetonitrile-0.025M phosphate buffer pH3.0.The test liquid preparation: precision takes by weighing this product 20mg and puts in the 2ml volumetric flask, and it is molten to scale to add 35: 65 acetonitrile-0.025M phosphate buffer pH3.0, and filtering with microporous membrane gets test liquid." an appendix VI of Chinese pharmacopoeia D measures according to high performance liquid chromatography, accurate respectively each the 10 μ l of cholic acid, hyodesoxycholic acid reference substance solution and test liquid that draw, inject high performance liquid chromatograph, chromatographic column C18ODS post, moving phase is with 30: 70 acetonitrile-0.025M phosphate pH3.0, flow velocity 1.0ml/min, and the detection wavelength is 205nm, measure cholic acid, hyodesoxycholic acid peak area integrated value, calculate with external standard method.This product contains cholic acid, hyodesoxycholic acid should be 90.0%～110.0% of labelled amount.
C. gardenoside:
The reference substance solution preparation, precision takes by weighing gardenoside standard items 1mg, puts in the 2ml volumetric flask, and it is molten to scale to add 30: 70 methanol-waters.The test liquid preparation: precision takes by weighing Qingkailing powder injection sample 5mg and puts in the 2ml volumetric flask, and it is molten to scale to add 30: 70 methanol-waters, and filtering with microporous membrane gets test liquid." an appendix VI of Chinese pharmacopoeia D measures according to high performance liquid chromatography, accurate respectively gardenoside reference substance solution and each 10 μ l of test liquid of drawing, inject high performance liquid chromatograph, chromatographic column C18ODS post, moving phase is with 20: 80 methanol-waters, flow velocity 1.0ml/min, and the detection wavelength is 237nm, measure gardenoside peak area integrated value, calculate with external standard method.This product contains gardenoside must not be less than 1.52%.
D. chlorogenic acid:
The reference substance solution preparation, precision takes by weighing chlorogenic acid standard items 1mg and puts in the 10ml volumetric flask, and it is molten to scale to add methyl alcohol.The test liquid preparation: precision takes by weighing sample 20mg, puts in the 2ml volumetric flask, and it is molten to scale to add methyl alcohol, and filtering with microporous membrane gets test liquid." an appendix VI of Chinese pharmacopoeia D measures according to high performance liquid chromatography, accurate respectively chlorogenic acid reference substance solution and each 10 μ l of test liquid of drawing, inject high performance liquid chromatograph, chromatographic column C18ODS post, moving phase is with 18: 82 acetonitrile-0.025M phosphate, flow velocity 1.0ml/min, and the detection wavelength is 326nm, measure chlorogenic acid peak area integrated value, calculate with external standard method.This product contains chlorogenic acid must not be less than 0.5%.
E. nitrogen content:
Precision takes by weighing Qingkailing powder injection sample 2mg, the photograph n2 method (" an appendix IX of Chinese pharmacopoeia nineteen ninety-five version L second method) measure, that is, this product nitrogenous (N) should be 90.0～120.0% of labelled amount.
Claims (1)
1. the method for quality control of baicalin in the QINGKAILING ZHUSHEYONG FENZHENJI, it comprises the steps: 1) get Qingkailing powder injection sample 3mg, accurate claim fixed, put in the 5ml volumetric flask, it is molten to scale to add methyl alcohol, and the aperture is 0.45 μ m filtering with microporous membrane, gets filtrate as test solution; 2) get the baicalin standard items in addition, the accurate title, decide, and adds dissolve with methanol and make the solution that every 1ml contains 50 μ g, in contrast product solution; 3) according to high effective liquid chromatography for measuring, accurate respectively baicalin reference substance solution and each 10 μ l of need testing solution of drawing, inject high performance liquid chromatograph, the acetonitrile of moving phase 28-40: 60-72-0.025M phosphoric acid, the detection wavelength is 276nm, measure the peak area integrated value, calculate promptly with external standard method, it is 90.0～110.0% of labelled amount that this product contains baicalin.
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| CN101231270B (en) * | 2007-01-23 | 2013-01-02 | 北京中医药大学 | Method for determining index composition content of Qingkailing injection intermediate body and finished product |
| CN104090056A (en) * | 2014-06-27 | 2014-10-08 | 上海雷允上药业有限公司 | Method for determining content of hyodeoxycholic acid in Beiling capsules through HPLC (High Performance Liquid Chromatography)-ELSD (Evaporative Light Scattering Detector) method |
| CN114042105A (en) * | 2021-12-27 | 2022-02-15 | 广州白云山明兴制药有限公司 | Preparation process of traditional Chinese medicine compound oral liquid |
| CN115990201B (en) * | 2022-11-08 | 2024-03-26 | 神威药业集团有限公司 | Preparation method of qingkailing preparation |
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| CN1145795A (en) * | 1995-09-16 | 1997-03-26 | 黄成钢 | Freeze-dried Qingkailing powder for injection |
| CN1160548A (en) * | 1996-03-29 | 1997-10-01 | 张家口市长城制药厂 | Process for producing Qingkailing powder injection |
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| CN1145795A (en) * | 1995-09-16 | 1997-03-26 | 黄成钢 | Freeze-dried Qingkailing powder for injection |
| CN1160548A (en) * | 1996-03-29 | 1997-10-01 | 张家口市长城制药厂 | Process for producing Qingkailing powder injection |
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