CN114225001B - 一种改良的大柴胡汤汤剂的制备方法 - Google Patents
一种改良的大柴胡汤汤剂的制备方法 Download PDFInfo
- Publication number
- CN114225001B CN114225001B CN202111682645.4A CN202111682645A CN114225001B CN 114225001 B CN114225001 B CN 114225001B CN 202111682645 A CN202111682645 A CN 202111682645A CN 114225001 B CN114225001 B CN 114225001B
- Authority
- CN
- China
- Prior art keywords
- decoction
- bupleurum
- baicalin
- critic
- markers
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 241000202726 Bupleurum Species 0.000 title claims abstract description 70
- 238000002360 preparation method Methods 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 57
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 claims abstract description 38
- 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 27
- 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 27
- 229960003321 baicalin Drugs 0.000 claims abstract description 27
- 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 27
- 238000012216 screening Methods 0.000 claims abstract description 21
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 claims abstract description 19
- 239000001606 7-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5-hydroxy-2-(4-hydroxyphenyl)chroman-4-one Substances 0.000 claims abstract description 19
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 claims abstract description 19
- YKRGDOXKVOZESV-WRJNSLSBSA-N Paeoniflorin Chemical compound C([C@]12[C@H]3O[C@]4(O)C[C@](O3)([C@]1(C[C@@H]42)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)C)OC(=O)C1=CC=CC=C1 YKRGDOXKVOZESV-WRJNSLSBSA-N 0.000 claims abstract description 19
- HIMJIPRMECETLJ-UHFFFAOYSA-N Wogonin Natural products COc1cc(O)c(O)c2C(=O)C=C(Oc12)c3ccccc3 HIMJIPRMECETLJ-UHFFFAOYSA-N 0.000 claims abstract description 19
- QUQPHWDTPGMPEX-UTWYECKDSA-N aurantiamarin Natural products COc1ccc(cc1O)[C@H]1CC(=O)c2c(O)cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)cc2O1 QUQPHWDTPGMPEX-UTWYECKDSA-N 0.000 claims abstract description 19
- APSNPMVGBGZYAJ-GLOOOPAXSA-N clematine Natural products COc1cc(ccc1O)[C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 APSNPMVGBGZYAJ-GLOOOPAXSA-N 0.000 claims abstract description 19
- 229940025878 hesperidin Drugs 0.000 claims abstract description 19
- VUYDGVRIQRPHFX-UHFFFAOYSA-N hesperidin Natural products COc1cc(ccc1O)C2CC(=O)c3c(O)cc(OC4OC(COC5OC(O)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 VUYDGVRIQRPHFX-UHFFFAOYSA-N 0.000 claims abstract description 19
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 claims abstract description 19
- DFPMSGMNTNDNHN-ZPHOTFPESA-N naringin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](OC=2C=C3O[C@@H](CC(=O)C3=C(O)C=2)C=2C=CC(O)=CC=2)O[C@H](CO)[C@@H](O)[C@@H]1O DFPMSGMNTNDNHN-ZPHOTFPESA-N 0.000 claims abstract description 19
- 229940052490 naringin Drugs 0.000 claims abstract description 19
- 229930019673 naringin Natural products 0.000 claims abstract description 19
- ARGKVCXINMKCAZ-UZRWAPQLSA-N neohesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@H]3[C@@H]([C@H](O)[C@@H](O)[C@H](C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UZRWAPQLSA-N 0.000 claims abstract description 19
- YKRGDOXKVOZESV-UHFFFAOYSA-N paeoniflorin Natural products O1C(C)(C2(CC34)OC5C(C(O)C(O)C(CO)O5)O)CC3(O)OC1C24COC(=O)C1=CC=CC=C1 YKRGDOXKVOZESV-UHFFFAOYSA-N 0.000 claims abstract description 19
- XLTFNNCXVBYBSX-UHFFFAOYSA-N wogonin Chemical compound COC1=C(O)C=C(O)C(C(C=2)=O)=C1OC=2C1=CC=CC=C1 XLTFNNCXVBYBSX-UHFFFAOYSA-N 0.000 claims abstract description 19
- WRYJYFCCMSVEPQ-ORAXXRKOSA-N Saikosaponin b2 Chemical compound O([C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@]([C@H]3[C@]([C@@H]4[C@@]([C@@]5(C[C@@H](O)[C@@]6(CO)CCC(C)(C)CC6=C5C=C4)C)(C)CC3)(C)CC2)(C)CO)O[C@@H]([C@@H]1O)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O WRYJYFCCMSVEPQ-ORAXXRKOSA-N 0.000 claims abstract description 15
- 239000013543 active substance Substances 0.000 claims abstract description 7
- 238000013461 design Methods 0.000 claims abstract description 7
- 230000000694 effects Effects 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- 238000001514 detection method Methods 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 239000000284 extract Substances 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 9
- 241000721047 Danaus plexippus Species 0.000 claims description 7
- 244000236658 Paeonia lactiflora Species 0.000 claims description 7
- 235000008598 Paeonia lactiflora Nutrition 0.000 claims description 7
- 238000002791 soaking Methods 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 241001522129 Pinellia Species 0.000 claims description 6
- 235000006886 Zingiber officinale Nutrition 0.000 claims description 6
- 238000010828 elution Methods 0.000 claims description 6
- 238000011156 evaluation Methods 0.000 claims description 6
- 235000008397 ginger Nutrition 0.000 claims description 6
- 239000011159 matrix material Substances 0.000 claims description 6
- 244000183685 Citrus aurantium Species 0.000 claims description 5
- 235000007716 Citrus aurantium Nutrition 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 239000003550 marker Substances 0.000 claims description 5
- 239000000047 product Substances 0.000 claims description 5
- 206010012735 Diarrhoea Diseases 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 238000009825 accumulation Methods 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 238000004458 analytical method Methods 0.000 claims description 4
- 239000002131 composite material Substances 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 239000010135 fructus aurantii immaturus Substances 0.000 claims description 4
- 230000003993 interaction Effects 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 239000012088 reference solution Substances 0.000 claims description 4
- 239000012488 sample solution Substances 0.000 claims description 4
- 239000000741 silica gel Substances 0.000 claims description 4
- 229910002027 silica gel Inorganic materials 0.000 claims description 4
- 239000011550 stock solution Substances 0.000 claims description 4
- 241000862992 Chondromyces Species 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 241000411851 herbal medicine Species 0.000 claims description 3
- 238000005259 measurement Methods 0.000 claims description 3
- 239000002674 ointment Substances 0.000 claims description 3
- BMWPBKOFJSHJAW-UHFFFAOYSA-N Saponin B Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(OC6OC(CO)C(O)C(OC7OC(CO)C(O)C(O)C7O)C6=O)C(C)(C)C5CCC34C)C2C1)C(=O)O BMWPBKOFJSHJAW-UHFFFAOYSA-N 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 230000000857 drug effect Effects 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000012528 membrane Substances 0.000 claims description 2
- 238000012545 processing Methods 0.000 claims description 2
- 239000013558 reference substance Substances 0.000 claims description 2
- 239000000523 sample Substances 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- 239000012085 test solution Substances 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 241000050051 Chelone glabra Species 0.000 claims 1
- 241000736199 Paeonia Species 0.000 claims 1
- 235000006484 Paeonia officinalis Nutrition 0.000 claims 1
- 206010037660 Pyrexia Diseases 0.000 claims 1
- 244000299790 Rheum rhabarbarum Species 0.000 claims 1
- 235000009411 Rheum rhabarbarum Nutrition 0.000 claims 1
- 244000273928 Zingiber officinale Species 0.000 claims 1
- 235000006545 Ziziphus mauritiana Nutrition 0.000 claims 1
- 244000126002 Ziziphus vulgaris Species 0.000 claims 1
- 235000008529 Ziziphus vulgaris Nutrition 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 6
- 238000000556 factor analysis Methods 0.000 abstract description 5
- 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 abstract description 2
- 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 abstract description 2
- 229940015301 baicalein Drugs 0.000 abstract description 2
- 230000007721 medicinal effect Effects 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 description 10
- 238000010926 purge Methods 0.000 description 10
- 240000004980 Rheum officinale Species 0.000 description 7
- 235000008081 Rheum officinale Nutrition 0.000 description 7
- 210000002784 stomach Anatomy 0.000 description 6
- 241000234314 Zingiber Species 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 4
- 206010047700 Vomiting Diseases 0.000 description 4
- 241001247821 Ziziphus Species 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 210000000232 gallbladder Anatomy 0.000 description 4
- 210000001835 viscera Anatomy 0.000 description 4
- 230000008673 vomiting Effects 0.000 description 4
- 240000004534 Scutellaria baicalensis Species 0.000 description 3
- 235000017089 Scutellaria baicalensis Nutrition 0.000 description 3
- 239000000919 ceramic Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000002023 wood Substances 0.000 description 3
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 208000019790 abdominal distention Diseases 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 244000010000 Hovenia dulcis Species 0.000 description 1
- 235000008584 Hovenia dulcis Nutrition 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 208000027697 autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/233—Bupleurum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/539—Scutellaria (skullcap)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/708—Rheum (rhubarb)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
- A61K36/725—Ziziphus, e.g. jujube
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
- A61K36/8888—Pinellia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9068—Zingiber, e.g. garden ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Medical Informatics (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Analytical Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Pathology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Neurosurgery (AREA)
- Gastroenterology & Hepatology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明在大柴胡汤汤剂制备方法的筛选过程中,首次引入Q‑markers概念,并根据Q‑markers筛选结果,将与大柴胡汤药效相关的主要活性物质柴胡皂苷B2、黄芩苷、黄芩素、汉黄芩苷、柚皮苷、新橙皮苷、橙皮苷和芍药苷作为筛选大柴胡汤汤剂制备方法的主要功效标志物,通过单因素分析和正交设计筛选出了一种改良的大柴胡汤汤剂的制备方法,通过该方法制备的大柴胡汤汤剂和解少阳、内泻热结功效显著提高。
Description
技术领域
本发明属于中药现代化领域,具体涉及一种改良的大柴胡汤汤剂的制备方法。
背景技术
大柴胡汤方出自张仲景的《伤寒杂病论》,由柴胡、黄芩、芍药、半夏、生姜、枳实、大枣、大黄组成,具有和解少阳,内泻热结之功。在中医的理论里,少阳包括胆与三焦,若少阳受邪,枢机不利,肝胆气机郁滞,必然影响三焦气化功能,若肝失疏泄,横逆犯胃,因而出现胸胁苦满,或胁下痞硬,或腹中痛等症,若伤及脾胃,气机壅塞,土壅木郁,燥热与糟粕互结,积于胃肠,阻滞腑气通降,可引起腹胀满而大便秘结等证候。由于少阳三焦为通行元气和运行水谷之要道,若邪热壅滞胆腑,上不得越,下不得泄,胆热木郁,克脾犯胃,胃失和降,可出现呕吐、泛酸、腹胀痛、纳差等病证。
方中柴胡专入少阳、疏邪透表为君药,黄芩擅清少阳之郁热,与柴胡同用,能和解少阳,是为少阳病未解、往来寒热、胸胁苦满而设;少用大黄泻热通腑,枳实行气破结,二者相配,可内泻热结,是为“热结在里”之心下痞满硬痛、大便不解、呕不止、郁郁微烦而设;芍药缓急止痛,配大黄可治腹中实痛,伍枳实能调和气血,协柴胡、黄芩清肝胆之热,以防木乘中土;半夏和胃降逆,生姜重用则止呕之功更著,以治呕逆不止;大枣和中益气,合芍药酸甘化阴,既可防热邪入里伤阴之虞,又能缓和枳实、大黄泻下伤阴之弊。总之,本方配伍体现了和解及攻下两法的结合运用,但以和解少阳为主、泻下之力较缓。
大柴胡汤在临床应用广泛,疗效稳定清晰,但其具体的功效物质基础尚不明确,并且目前大柴胡汤的制备方法、检测方法均不够完善,没有标准的制备工艺流程,大柴胡汤质量标准也不完善,导致临床上使用的大柴胡汤的质量参差不齐,使得大柴胡汤的临床功效大打折扣。
因此,寻找一种能够使得大柴胡汤中主要药效成分的含量增加的改良的大柴胡汤汤剂的制备方法,是目前急需解决的问题。
发明内容
为了解决上述技术问题,本发明在改良的大柴胡汤汤剂制备方法的筛选过程中首次引入Q-markers概念,筛选出了一种改良的大柴胡汤汤剂的制备方法,通过该方法制备的改良的大柴胡汤汤剂具有显著提高的和解少阳内泻热结功效。
具体地,通过以下几个方面的技术方案实现了本发明:
在第一个方面中,本发明提供了一种改良的大柴胡汤汤剂的制备方法,所述制备方法包括以下步骤:
取适量制备大柴胡汤所需的各种中药材,加水8-12倍,武火煎煮至沸腾,后文火煎煮20-50min,得适量煎煮液,过滤去渣滓,重复煎煮2-4次,合并滤液后,再文火煎煮20-50min,浓缩煎液,得到改良的大柴胡汤汤剂,所述中药材为柴胡、黄芩、芍药、半夏、枳实、生姜、大枣和大黄。
作为可选的方式,在上述制备方法中,所述改良的大柴胡汤汤剂的出膏率为15%-30%。
优选地,所述出膏率为25%-30%。
作为可选的方式,在上述制备方法中,所述方法制备得到的改良的大柴胡汤汤剂中主要活性物质柴胡皂苷B2、黄芩苷、黄芩素、汉黄芩苷、柚皮苷、新橙皮苷、橙皮苷和芍药苷的含量显著增加,且所述方法制备得到的改良的大柴胡汤汤剂和解少阳内泻热结的功效显著增强。
作为可选的方式,在上述制备方法中,制备大柴胡汤所需的各种中药材以重量计分别为:柴胡22.08g、黄芩8.28g、芍药8.28g、半夏12.00g、枳实11.66g、生姜13.80g、大枣11.04g和大黄5.52g。
作为可选的方式,在上述制备方法中,所述制备方法优选包括以下步骤:
取适量制备大柴胡汤所需的各种中药材,加水10倍,武火煎煮至沸腾,后文火煎煮40min,得适量煎煮液,过滤去渣滓,重复煎煮3次,合并滤液后,再文火煎煮25min,浓缩煎液,得到改良的大柴胡汤汤剂。
在第二个方面中,本发明提供了上述第一个方面所述的改良的大柴胡汤汤剂制备方法的筛选方法,其特征在于:所述筛选方法包括以下步骤:
(1)通过大柴胡汤功效Q-markers精准分析发现与特定功效对应的一种或多种活性成分;
(2)以步骤(1)中的与特定功效对应的活性成分作为药效标志物(Q-markers),利用高效液相色谱法(HPLC)测量采用候选煎煮条件制备得到的大柴胡汤汤剂中所述一种或多种Q-markers的含量;和
(3)选择所述大柴胡汤汤剂中所述一种或多种Q-markers的含量较高和出膏率较高的煎煮条件,将其作为改良的大柴胡汤汤剂的制备方法。
作为可选的方式,在上述筛选方法中,所述Q-markers为柴胡皂苷B2、黄芩苷、黄芩素、汉黄芩苷、柚皮苷、新橙皮苷、橙皮苷和芍药苷。
作为可选的方式,在上述筛选方法中,所述HPLC包括以下步骤:
(1)将大柴胡汤制成供试品溶液:
将待测大柴胡汤煎液定容于250mL容量瓶中,精密量取1mL,置10mL的容量瓶内,加入一定量有机溶剂,摇匀,超声提取10min,静置,放冷,用有机溶剂定容至刻度线,摇匀,过0.22μm微孔滤膜,取续滤液,即得供试品溶液;
(2)制备对照品溶液:
精密称取芍药苷对照品11.30mg、柚皮苷对照品11.26mg、橙皮苷11.30mg、新橙皮苷10.90mg、黄芩苷11.55mg、汉黄芩苷5.30mg、柴胡皂苷B2 5.36mg、黄芩素4.80mg置于10mL容量瓶内,加有机溶剂使溶解并定容摇匀,作为储备液,精密移取上述储备液各1mL,置10mL容量瓶中,有机溶剂定容,摇匀,即得混合对照品溶液;
以及,(3)对所述供试品溶液和所述对照品溶液进行HPLC检测,以测定大柴胡汤Q-markers的含量:
其中,HPLC检测的色谱条件如下所示:采用ODS-C18硅胶色谱柱,以A相乙腈和B相0.05%磷酸水溶液作为流动相,紫外检测器,检测波长为230nm-280nm,流速1.0mL·min-1,柱温:25-35℃,进样体积10μL。
优选地,在步骤(1)和步骤(2)中的有机溶剂为甲醇。
优选地,在步骤(3)中采用的洗脱方式为梯度洗脱,洗脱条件为:0-5min,3%-3%A;5-10min,3%-10%A;10-15min,10%-12%A;15-25min,12%-16%A;25-30min,16%-16%A;30-50min,16%-20%A;50-55min,20%-20%A;55-75min,20%-25%A;75-85min,25%-46%A;85-90min,46%-85%A;90-100min,85%-85%A。
优选地,在步骤(3)中,使用ODS-C18硅胶色谱柱,规格为4.6×250mm,5μm,检测波长如下所示:芍药苷230nm,柴胡皂苷B2 254nm,柚皮苷、橙皮苷、新橙皮苷、黄芩苷、黄芩素和汉黄芩苷280nm,柱温为30℃。
作为可选的方式,在上述筛选方法中,所述候选煎煮条件是通过单因素分析和正交设计获得的,所述煎煮条件为浸泡时间、加水量、煎煮次数和/或煎煮时间。
在第三个方面中,本发明提供了上述第一个方面所述的制备方法制备得到的改良的大柴胡汤汤剂,所述改良的大柴胡汤汤剂中主要活性物质柴胡皂苷B2、黄芩苷、黄芩素、汉黄芩苷、柚皮苷、新橙皮苷、橙皮苷和芍药苷的含量显著增加,且所述方法制备得到的改良的大柴胡汤汤剂和解少阳、内泻热结的功效显著增强。
本发明相对于现有技术,具有以下有益效果:
本发明在改良的大柴胡汤汤剂制备方法的筛选过程中,首次引入Q-markers概念,并根据Q-markers筛选结果,将与大柴胡汤药效相关的主要活性物质柴胡皂苷B2、黄芩苷、黄芩素、汉黄芩苷、柚皮苷、新橙皮苷、橙皮苷和芍药苷作为筛选改良的大柴胡汤汤剂的制备方法的主要功效标志物,通过单因素分析和正交设计筛选出了一种改良的大柴胡汤汤剂的制备方法,通过该方法制备的改良的大柴胡汤汤剂具有显著提高的和解少阳、内泻热结功效。
附图说明
附图用来提供对本发明的进一步理解,并且构成说明书的一部分,与本发明的实施例一起用于解释本发明,并不构成对本发明的限制。在附图中:
图1:大柴胡汤功效Q-makers精准分析的流程图。
具体实施方式
下面参照具体的实施例对本发明做进一步说明。应当理解,此处所描述的具体实施例仅用于解释本发明,并不用于限定本发明的范围。
实施例中未注明具体技术或条件者,按照本领域内的文献所描述的技术或条件,或者按照产品说明书进行。所用试剂或仪器未注明生产厂商者,均为可通过正规渠道购买得到的常规产品。
下面实施例中的实验方法,如无特殊说明,均为常规方法。下述实施例中所用的试验材料,如无特殊说明,均为市售产品。
实施例:
1.与大柴胡汤和解少阳内泻热结功效对应的Q-markers的筛选
采用如图1中所示的流程对与大柴胡汤和解少阳内泻热结功效对应的Q-markers进行筛选,结果如下表1所示。
表1:与大柴胡汤和解少阳内泻热结功效对应的Q-markers
注:加粗的药效为关键药效;加粗的成分为Q-markers。
如表1中所示,根据Q-markers筛选结果,将与大柴胡汤药效相关的主要活性物质柴胡皂苷B2、黄芩苷、黄芩素、汉黄芩苷、柚皮苷、新橙皮苷、橙皮苷和芍药苷作为筛选改良的大柴胡汤汤剂的制备方法的主要功效标志物。
因此,通过对上述功效标志物进行含量测定筛选出的改良的大柴胡汤汤剂制备方法制备出的大柴胡汤汤剂应当具有显著提高的和解少阳内泻热结功效。
2.改良的大柴胡汤汤剂制备方法的单因素分析
在以下研究中,制备大柴胡汤所需的各种中药材以重量计分别为:柴胡22.08g、黄芩8.28g、芍药8.28g、半夏12.00g、枳实11.66g、生姜13.80g、大枣11.04g和大黄5.52g。
2.1浸泡时间的考察
加5倍量的水,分别浸泡0min、15min、30min、45min、60min,武火煮沸,后改为文火煎煮25min,后去渣滓继续文火浓缩,使每份所得药液体积为120mL,定容于250mL容量瓶中,每份平行两次。汤剂中8种指标性成分测定,结果如表2。
取煎煮液50mL,置已干燥至恒重的陶瓷蒸发皿中,于100℃水浴锅上蒸干,再置105℃烘箱中干燥3h后取出,放入干燥器中冷却0.5h,迅速称定质量,计算浸膏得率,结果如表2。
综合考虑,得浸泡时间为30min时,效果较优。
表2:不同浸泡时间煎液中功效标志物含量测定结果(mg·mL-1)
2.2加水量
分别加5倍、7倍、9倍、11倍量的水,无浸泡,武火煮沸,后改为文火,煎煮,使煎液体积为250mL后去渣滓再煎,使每份所得药液均浓缩到120mL,定容于250mL容量瓶中,每份平行两次。汤剂中8种指标性成分测定,结果如表3。
取煎煮液50mL,置已干燥至恒重的陶瓷蒸发皿中,于100℃水浴锅上蒸干,再置105℃烘箱中干燥3h后取出,放入干燥器中冷却0.5h,迅速称定质量,计算浸膏得率,结果如表3。
综合考虑,加水量为9倍时,效果较优。
表3:不同加水量煎液中功效标志物含量测定结果(mg·mL-1)
2.3煎煮时间
分别加5倍倍量的水,无浸泡,武火煮沸,后改为文火,煎煮15min、25min、35min,后去渣滓再煎,使每份所得药液均浓缩到120mL,定容于250mL容量瓶中,每份平行两次。汤剂中8种指标性成分测定,结果如表4。
取煎煮液50mL,置已干燥至恒重的陶瓷蒸发皿中,于100℃水浴锅上蒸干,再置105℃烘箱中干燥3h后取出,放入干燥器中冷却0.5h,迅速称定质量,计算浸膏得率,结果如表4。
综合考虑,煎煮时间为35min时,效果较优。
表4:不同煎煮时间煎液中功效标志物含量测定结果(mg·mL-1))
综上,得到单因素为浸泡30min、加9倍量水、煎煮35min时得到的煎液较优,在此基础上对正交因素水平数进行设计。
3.改良的大柴胡汤汤剂制备方法的正交设计
3.1各因素及水平数
表5:各因素及水平数
3.2综合评价法
其评价方法采用APH-CRITIC混合加权方法,得到评价指标(Q-markers的含量及出膏率)的权重系数为二者权重系数的乘积占乘积之和的比例,从而对其进行综合评价。将AHP法和CRITIC法分别得到的权重系数进行混合加权,既反映了中药复方君臣佐使的配伍规律,又客观反映了各组分间的相互作用。
大柴胡汤中的柴胡为君药,其对应指标成分柴胡皂苷B2作为第一层次;枳实、黄芩为臣药,含有柚皮苷、橙皮苷、新橙皮苷、黄芩苷、汉黄芩苷、黄芩素,作为第二层次;白芍为佐药,含有芍药苷为第三层次;浸膏得率为第四层次,获得各项指标的AHP的权重系数,其矩阵图如表6。一致性比例因子CR=0.0022771<0.10,表明此判断矩阵具有满意的一致性,权重系数有效。计算柴胡皂苷B2、柚皮苷、橙皮苷、新橙皮苷、黄芩苷、汉黄芩苷、黄芩素、芍药苷、浸膏得率9项指标的权重系数分别为0.2123、0.1146、0.1146、0.1146、0.1146、0.1146、0.1146、0.0611、0.0387。
表6:指标成对比较的判断优先矩阵
CRITIC法是一种客观权重赋权法,可以客观的计算出各指标的权重系数,可以消除主观确定权重系数的人为因素。首先对数据进行无量纲化处理,即指标性成分无量纲化数据=(实测值-最低值)/(最高值-最低值)×100。用SPSS 22.0统计软件处理无量纲化数据,得相关系数矩阵,计算相关数据:各指标对比强度(si)、冲突性(δi)、综合权重(ci)与权重(ωi),结果见表7。
表7:CRITIC法相关计算数据
AHP-CRITIC混合加权法确定权重系数:大柴胡汤由多味药组成,将AHP法和CRITIC法分别得到的权重系数进行混合加权,既反映了中药复方君臣佐使的配伍规律,又客观反映了各组分间的相互作用,AHP-CRITIC混合加权法较单用AHP法和CRITIC法确定权重系数更加科学合理。即ω综合=ωAHPωCRITIC/∑ωAHPωCRITIC,ωAHP表示AHP法计算的权重系数,ωCRITIC表示CRITIC法计算的权重系数,通过计算得胡皂苷B2、柚皮苷、橙皮苷、新橙皮苷、黄芩苷、汉黄芩苷、黄芩素、芍药苷、浸膏得率9项指标的权重系数分别为0.2469、0.0791、0.0772、0.0887、0.0781、0.0741、0.1312、0.1937、0.0311。
3.3正交实验结果
综合评分=∑(成分含量/成分最大含量)×综合权重系数,结果见表8。方差分析见表9。
表9:大柴胡汤煎煮工艺方差分析结果
直观分析,各因素对提取工艺的影响顺序为B>A>C,方差结果得煎煮次数不同其有显著性差异。因此确定最优得煎煮工艺为A3B3C2,即加水量为10倍,煎煮3次,每次40min
综上所述,本发明在改良的大柴胡汤汤剂制备方法的筛选过程中,首次引入Q-markers概念,并根据Q-markers筛选结果,将与大柴胡汤药效相关的主要活性物质柴胡皂苷B2、黄芩苷、黄芩素、汉黄芩苷、柚皮苷、新橙皮苷、橙皮苷和芍药苷作为筛选改良的大柴胡汤汤剂制备方法的主要功效标志物,通过单因素分析和正交设计筛选出了一种改良的大柴胡汤汤剂的制备方法,通过该方法制备的改良的大柴胡汤汤剂具有显著提高的和解少阳内泻热结功效。
显然,本领域的技术人员可以对本发明进行各种改动和变型而不脱离本发明的精神和范围。这样,倘若本发明的这些修改和变型属于本发明权利要求及其等同技术的范围之内,则本发明也意图包含这些改动和变型在内。
Claims (2)
1.一种改良的大柴胡汤汤剂制备方法的筛选方法,其特征在于:所述筛选方法包括以下步骤:
(1)通过大柴胡汤功效Q-markers精准分析发现与特定功效对应的一种或多种活性成分;
(2)以步骤(1)中的与特定功效对应的活性成分作为药效标志物Q-markers,利用高效液相色谱法测量采用候选煎煮条件制备得到的大柴胡汤汤剂中所述Q-markers的含量;和
(3)选择所述大柴胡汤汤剂中所述Q-markers的含量较高和出膏率较高的煎煮条件,将其作为改良的大柴胡汤汤剂的制备方法,
所述Q-markers为柴胡皂苷B2、黄芩苷、黄芩素、汉黄芩苷、柚皮苷、新橙皮苷、橙皮苷和芍药苷,所述特定功效为大柴胡汤和解少阳、内泻热结的功效,
所述候选煎煮条件是通过APH-CRITIC混合加权方法和正交设计获得的,所述煎煮条件为浸泡时间、加水量、煎煮次数和煎煮时间,具体为:
采用APH-CRITIC混合加权方法,得到评价指标(Q-markers的含量及出膏率)的权重系数为二者权重系数的乘积占乘积之和的比例,从而对其进行综合评价;将AHP法和CRITIC法分别得到的权重系数进行混合加权,既反映了中药复方君臣佐使的配伍规律,又客观反映了各组分间的相互作用;
大柴胡汤中的柴胡为君药,其对应指标成分柴胡皂苷B2作为第一层次;枳实、黄芩为臣药,含有柚皮苷、橙皮苷、新橙皮苷、黄芩苷、汉黄芩苷、黄芩素,作为第二层次;白芍为佐药,含有芍药苷为第三层次;浸膏得率为第四层次,获得各项指标的AHP的权重系数,一致性比例因子CR=0.0022771<0.10,表明此判断矩阵具有满意的一致性,权重系数有效;计算柴胡皂苷B2、柚皮苷、橙皮苷、新橙皮苷、黄芩苷、汉黄芩苷、黄芩素、芍药苷、浸膏得率9项指标的权重系数分别为0.2123、0.1146、0.1146、0.1146、0.1146、0.1146、0.1146、0.0611、0.0387;
CRITIC法是一种客观权重赋权法,可以客观的计算出各指标的权重系数,可以消除主观确定权重系数的人为因素;首先对数据进行无量纲化处理,即指标性成分无量纲化数据=(实测值-最低值)/(最高值-最低值)×100;用SPSS 22.0统计软件处理无量纲化数据,得相关系数矩阵,计算相关数据:各指标对比强度si、冲突性δi、综合权重ci与权重ωi;
AHP-CRITIC混合加权法确定权重系数:大柴胡汤由多味药组成,将AHP法和CRITIC法分别得到的权重系数进行混合加权,既反映了中药复方君臣佐使的配伍规律,又客观反映了各组分间的相互作用,AHP-CRITIC混合加权法较单用AHP法和CRITIC法确定权重系数更加科学合理;即ω综合=ωAHPωCRITIC/∑ωAHPωCRITIC,ωAHP表示AHP法计算的权重系数,ωCRITIC表示CRITIC法计算的权重系数,通过计算得胡皂苷B2、柚皮苷、橙皮苷、新橙皮苷、黄芩苷、汉黄芩苷、黄芩素、芍药苷、浸膏得率9项指标的权重系数分别为0.2469、0.0791、0.0772、0.0887、0.0781、0.0741、0.1312、0.1937、0.0311;
在正交设计中,综合评分=∑(成分含量/成分最大含量)×综合权重系数;
制备所述大柴胡汤所需的各种中药材为柴胡、黄芩、芍药、半夏、枳实、生姜、大枣和大黄,
所述HPLC包括以下步骤:
(1)将大柴胡汤制成供试品溶液:
将待测大柴胡汤煎液定容于250mL容量瓶中,精密量取1mL,置10mL的容量瓶内,加入一定量有机溶剂,摇匀,超声提取10min,静置,放冷,用有机溶剂定容至刻度线,摇匀,过0.22μm微孔滤膜,取续滤液,即得供试品溶液;
(2)制备对照品溶液:
精密称取芍药苷对照品11.30mg、柚皮苷对照品11.26mg、橙皮苷11.30mg、新橙皮苷10.90mg、黄芩苷11.55mg、汉黄芩苷5.30mg、柴胡皂苷B25.36 mg、黄芩素4.80mg置于10mL容量瓶内,加有机溶剂使溶解并定容摇匀,作为储备液,精密移取上述储备液各1mL,置10mL容量瓶中,有机溶剂定容,摇匀,即得混合对照品溶液;
以及,(3)对所述供试品溶液和所述对照品溶液进行HPLC检测,以测定大柴胡汤Q-markers的含量:
其中,HPLC检测的色谱条件如下所示:采用ODS-C18硅胶色谱柱,以A相乙腈和B相0.05%磷酸水溶液作为流动相,紫外检测器,检测波长为230nm-280nm,流速1.0mL·min-1,柱温:25-35℃,进样体积10μL,
在所述HPLC的步骤(1)和步骤(2)中的有机溶剂为甲醇,
在所述HPLC的步骤(3)中采用的洗脱方式为梯度洗脱,洗脱条件为:0-5min,3%-3%A;5-10min,3%-10%A;10-15min,10%-12%A;15-25min,12%-16%A;25-30min,16%-16%A;30-50min,16%-20%A;50-55min,20%-20%A;55-75min,20%-25%A;75-85min,25%-46%A;85-90min,46%-85%A;90-100min,85%-85%A,
在所述HPLC的步骤(3)中,使用ODS-C18硅胶色谱柱,规格为4.6×250mm,5μm,检测波长如下所示:芍药苷230nm,柴胡皂苷B2254 nm,柚皮苷、橙皮苷、新橙皮苷、黄芩苷、黄芩素和汉黄芩苷280nm,柱温为30℃。
2.一种由权利要求1所述筛选方法获得的大柴胡汤汤剂的制备方法,其特征在于,所述制备方法包括以下步骤:
取适量制备大柴胡汤所需的各种中药材,加水10倍,武火煎煮至沸腾,后文火煎煮40min,得适量煎煮液,过滤去渣滓,重复煎煮3次,合并滤液后,再文火煎煮25min,浓缩煎液,得到改良的大柴胡汤汤剂,
制备大柴胡汤所需的各种中药材以重量计分别为:柴胡22.08g、黄芩8.28g、芍药8.28g、半夏12.00g、枳实11.66g、生姜13.80g、大枣11.04g和大黄5.52g,所述改良的大柴胡汤汤剂的出膏率为25-30%,所述方法制备得到的改良的大柴胡汤汤剂中主要活性物质柴胡皂苷B2、黄芩苷、黄芩素、汉黄芩苷、柚皮苷、新橙皮苷、橙皮苷和芍药苷的含量显著增加,且所述方法制备得到的改良的大柴胡汤汤剂和解少阳、内泻热结的功效显著增强。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111682645.4A CN114225001B (zh) | 2021-12-31 | 2021-12-31 | 一种改良的大柴胡汤汤剂的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111682645.4A CN114225001B (zh) | 2021-12-31 | 2021-12-31 | 一种改良的大柴胡汤汤剂的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114225001A CN114225001A (zh) | 2022-03-25 |
CN114225001B true CN114225001B (zh) | 2024-04-19 |
Family
ID=80745582
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111682645.4A Active CN114225001B (zh) | 2021-12-31 | 2021-12-31 | 一种改良的大柴胡汤汤剂的制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114225001B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114324667B (zh) * | 2021-12-31 | 2024-04-19 | 北京橘井健康科技集团有限公司 | 一种大柴胡汤hplc特征图谱构建方法及含量测定方法 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06166629A (ja) * | 1992-08-06 | 1994-06-14 | Tsumura & Co | アトピー性皮膚炎改善剤 |
CN1706417A (zh) * | 2004-06-05 | 2005-12-14 | 余世春 | 小柴胡汤口服液的制备方法及其质量控制技术 |
JP2012087055A (ja) * | 2010-10-15 | 2012-05-10 | Sakamoto Kanpo Seiyaku:Kk | 生薬含有製剤 |
CN102847089A (zh) * | 2011-06-30 | 2013-01-02 | 苏州知微堂生物科技有限公司 | 一种大柴胡汤整合型新剂型制备技术及其生产方法 |
CN107629108A (zh) * | 2017-09-22 | 2018-01-26 | 山西中医药大学 | 一种柴胡药材中柴胡皂苷a、c、d的提取方法 |
CN108635552A (zh) * | 2018-05-18 | 2018-10-12 | 广州志道经方科技有限公司 | 一种大柴胡汤固体制剂的制备工艺 |
-
2021
- 2021-12-31 CN CN202111682645.4A patent/CN114225001B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06166629A (ja) * | 1992-08-06 | 1994-06-14 | Tsumura & Co | アトピー性皮膚炎改善剤 |
CN1706417A (zh) * | 2004-06-05 | 2005-12-14 | 余世春 | 小柴胡汤口服液的制备方法及其质量控制技术 |
JP2012087055A (ja) * | 2010-10-15 | 2012-05-10 | Sakamoto Kanpo Seiyaku:Kk | 生薬含有製剤 |
CN102847089A (zh) * | 2011-06-30 | 2013-01-02 | 苏州知微堂生物科技有限公司 | 一种大柴胡汤整合型新剂型制备技术及其生产方法 |
CN107629108A (zh) * | 2017-09-22 | 2018-01-26 | 山西中医药大学 | 一种柴胡药材中柴胡皂苷a、c、d的提取方法 |
CN108635552A (zh) * | 2018-05-18 | 2018-10-12 | 广州志道经方科技有限公司 | 一种大柴胡汤固体制剂的制备工艺 |
Non-Patent Citations (5)
Title |
---|
Development and Validation of an HPLC Method for Simultaneous Determination of Nine Active Components in ‘Da-Chai-Hu-Tang’;LingliZheng;《Chinese Medicine》;20110331;第2卷;第20-28页 * |
High-performance liquid chromatographic method for simultaneous quantification of eight major biologically active ingredients in ‘Da-Chai-Hu-Tang’ Preparation;Chia Ying Li;《BIOMEDICAL CHROMATOGRAPHY》;20050930;第20卷(第4期);第305-308页 * |
吕志杰.大柴胡汤.《张仲景方剂学》.中国医药科技出版社,2018,(第3版),第194页. * |
徐晓玉.中药药理学.中国中医药出版社,2010,(第1版),136-138. * |
樊代明.整合医学:理论与实践.世界图书出版社西安有限公司,2019,(第1版),524. * |
Also Published As
Publication number | Publication date |
---|---|
CN114225001A (zh) | 2022-03-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Xiong et al. | Chinese herbal medicine for coronavirus disease 2019: A systematic review and meta-analysis | |
CN106501434B (zh) | 一种双和汤标准汤的hplc指纹图谱测定方法 | |
WO2022036781A1 (zh) | 化湿败毒组合物的质量控制方法 | |
CN105687994B (zh) | 一种治疗慢性肾功能衰竭的中药组合物及其制备方法 | |
CN111735889B (zh) | 化湿败毒组合物的质量检测方法 | |
CN111735896B (zh) | 化湿败毒组合物特征图谱的构建方法 | |
TWI275397B (en) | Herbal composition, use thereof in protection of endothelial cell and in anti-inflammation, and preparation method thereof | |
CN114225001B (zh) | 一种改良的大柴胡汤汤剂的制备方法 | |
CN101254284B (zh) | 一种治疗风湿病的药物组合物及制备方法和检测方法 | |
CN113156001A (zh) | 一种包含当归的中药复方的指纹图谱构建方法及其应用 | |
Fang et al. | Shengyu Decoction treating vascular cognitive impairment by promoting AKT/HIF-1α/VEGF related cerebrovascular generation and ameliorating MAPK/NF-κB mediated neuroinflammation | |
CN114324667B (zh) | 一种大柴胡汤hplc特征图谱构建方法及含量测定方法 | |
CN105267559A (zh) | 一种治疗糖尿病周围神经病变的药物及其制作方法 | |
CN111429978A (zh) | 一种快速发现中药复方有效组分的方法和应用 | |
CN102861159B (zh) | 一种治疗痛经的药物组合物及其制备方法和用途 | |
WO2022036780A1 (zh) | 化湿败毒组合物的检测方法 | |
CN102049012B (zh) | 一种治疗儿童性早熟的中药组合物及其制备和检测方法 | |
CN106038679B (zh) | 一种对颈椎病和失眠均具有治疗作用药物及其制备方法 | |
CN101254260A (zh) | 一种治疗前列腺增生、尿闭的药物组合物及制备方法 | |
CN100376284C (zh) | 一种主治子宫肌瘤的中成药和制备、质量控制方法 | |
AU783302B2 (en) | Composition of traditional chinese medicines for preventing and treating cerebrovascular disease | |
CN102028828A (zh) | 一种治疗前列腺增生、尿闭的药物组合物及检测方法 | |
CN103007001B (zh) | 一种治疗睡眠障碍的中药制剂及其制备方法 | |
CN115389660B (zh) | 一种治疗膝骨性关节炎的中药复方组合物及其质量检测方法 | |
EP1358887A1 (en) | Composition of traditional chinese medicines for preventing and treating cerebrovascular disease |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |