CN104490990A - Method for preparing Fengshiding tablets - Google Patents
Method for preparing Fengshiding tablets Download PDFInfo
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- CN104490990A CN104490990A CN201410834244.XA CN201410834244A CN104490990A CN 104490990 A CN104490990 A CN 104490990A CN 201410834244 A CN201410834244 A CN 201410834244A CN 104490990 A CN104490990 A CN 104490990A
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- CN
- China
- Prior art keywords
- radix
- paeonol
- add
- water
- cynanchi paniculati
- Prior art date
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- 238000000034 method Methods 0.000 title abstract description 16
- UILPJVPSNHJFIK-UHFFFAOYSA-N Paeonol Chemical compound COC1=CC=C(C(C)=O)C(O)=C1 UILPJVPSNHJFIK-UHFFFAOYSA-N 0.000 claims abstract description 187
- YLTGFGDODHXMFB-UHFFFAOYSA-N isoacetovanillon Natural products COC1=CC=C(C(C)=O)C=C1O YLTGFGDODHXMFB-UHFFFAOYSA-N 0.000 claims abstract description 93
- MLIBGOFSXXWRIY-UHFFFAOYSA-N paeonol Natural products COC1=CC=C(O)C(C(C)=O)=C1 MLIBGOFSXXWRIY-UHFFFAOYSA-N 0.000 claims abstract description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 73
- 239000000843 powder Substances 0.000 claims abstract description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 40
- 239000000706 filtrate Substances 0.000 claims abstract description 33
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 30
- 238000002360 preparation method Methods 0.000 claims abstract description 28
- 238000002156 mixing Methods 0.000 claims abstract description 26
- 239000003814 drug Substances 0.000 claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 239000008187 granular material Substances 0.000 claims abstract description 18
- 239000000463 material Substances 0.000 claims abstract description 18
- 238000001035 drying Methods 0.000 claims abstract description 17
- 238000009495 sugar coating Methods 0.000 claims abstract description 16
- 239000011780 sodium chloride Substances 0.000 claims abstract description 15
- 229940079593 drug Drugs 0.000 claims abstract description 13
- 239000007788 liquid Substances 0.000 claims description 26
- 239000012467 final product Substances 0.000 claims description 21
- 238000002425 crystallisation Methods 0.000 claims description 18
- 230000008025 crystallization Effects 0.000 claims description 18
- 238000004821 distillation Methods 0.000 claims description 18
- 239000012567 medical material Substances 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 230000001476 alcoholic effect Effects 0.000 claims description 11
- 239000000084 colloidal system Substances 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 8
- 206010013786 Dry skin Diseases 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- YMGFTDKNIWPMGF-QHCPKHFHSA-N Salvianolic acid A Natural products OC(=O)[C@H](Cc1ccc(O)c(O)c1)OC(=O)C=Cc2ccc(O)c(O)c2C=Cc3ccc(O)c(O)c3 YMGFTDKNIWPMGF-QHCPKHFHSA-N 0.000 claims description 2
- YMGFTDKNIWPMGF-UCPJVGPRSA-N Salvianolic acid A Chemical compound C([C@H](C(=O)O)OC(=O)\C=C\C=1C(=C(O)C(O)=CC=1)\C=C\C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 YMGFTDKNIWPMGF-UCPJVGPRSA-N 0.000 claims description 2
- 229930183842 salvianolic acid Natural products 0.000 claims description 2
- 238000012216 screening Methods 0.000 abstract description 7
- 239000000047 product Substances 0.000 abstract description 5
- 238000000227 grinding Methods 0.000 abstract description 3
- 241001233914 Chelidonium majus Species 0.000 abstract 4
- 238000001914 filtration Methods 0.000 abstract 3
- 241000864411 Alangium platanifolium Species 0.000 abstract 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 abstract 1
- 244000303040 Glycyrrhiza glabra Species 0.000 abstract 1
- 238000001816 cooling Methods 0.000 abstract 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 abstract 1
- 235000011477 liquorice Nutrition 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 32
- 229930013930 alkaloid Natural products 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 238000000605 extraction Methods 0.000 description 11
- 150000003797 alkaloid derivatives Chemical class 0.000 description 9
- 239000013558 reference substance Substances 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 231100000614 poison Toxicity 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- REZQBEBOWJAQKS-UHFFFAOYSA-N triacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO REZQBEBOWJAQKS-UHFFFAOYSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- IOIGOIPHPUCFOB-IMTBSYHQSA-N (6r,7s)-7-methyl-6,7-dihydro-5h-cyclopenta[c]pyridin-6-ol Chemical compound C1=NC=C2[C@H](C)[C@H](O)CC2=C1 IOIGOIPHPUCFOB-IMTBSYHQSA-N 0.000 description 3
- IOIGOIPHPUCFOB-UHFFFAOYSA-N Gentialutine Natural products C1=NC=C2C(C)C(O)CC2=C1 IOIGOIPHPUCFOB-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 230000007096 poisonous effect Effects 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 239000001116 FEMA 4028 Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 2
- PDNLMONKODEGSE-UHFFFAOYSA-N beta-amyrin acetate Natural products CC(=O)OC1CCC2(C)C(CCC3(C)C4(C)CCC5(C)CCC(C)(C)CC5C4=CCC23C)C1(C)C PDNLMONKODEGSE-UHFFFAOYSA-N 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 2
- 239000002574 poison Substances 0.000 description 2
- 230000006340 racemization Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000003809 water extraction Methods 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 1
- 241000219112 Cucumis Species 0.000 description 1
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 description 1
- 241000202807 Glycyrrhiza Species 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000008765 Sciatica Diseases 0.000 description 1
- FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical compound N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- FSLPMRQHCOLESF-UHFFFAOYSA-N alpha-amyrenol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C)CCC(C)C(C)C5C4=CCC3C21C FSLPMRQHCOLESF-UHFFFAOYSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 229940076810 beta sitosterol Drugs 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- JFSHUTJDVKUMTJ-QHPUVITPSA-N beta-amyrin Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C JFSHUTJDVKUMTJ-QHPUVITPSA-N 0.000 description 1
- QQFMRPIKDLHLKB-UHFFFAOYSA-N beta-amyrin Natural products CC1C2C3=CCC4C5(C)CCC(O)C(C)(C)C5CCC4(C)C3(C)CCC2(C)CCC1(C)C QQFMRPIKDLHLKB-UHFFFAOYSA-N 0.000 description 1
- UMRPOGLIBDXFNK-ZYGITSNFSA-N beta-amyrin acetate Chemical compound C([C@H]1C2=CC[C@H]34)C(C)(C)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](OC(=O)C)C1(C)C UMRPOGLIBDXFNK-ZYGITSNFSA-N 0.000 description 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000003177 cardiotonic effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000002951 street drug Substances 0.000 description 1
- 231100000456 subacute toxicity Toxicity 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 239000002023 wood Substances 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)
-
- 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
- A61K36/232—Angelica
-
- 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)
- A61K36/27—Asclepiadaceae (Milkweed family), e.g. hoya
-
- 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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/484—Glycyrrhiza (licorice)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
- A61K9/2826—Sugars or sugar alcohols, e.g. sucrose; Derivatives thereof
-
- 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
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/15—Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding
-
- 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 or 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
-
- 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
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Inorganic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention belongs to the field of medicines and relates to a method for preparing Fengshiding tablets. The preparation method disclosed by the invention comprises the following steps: grinding radix angelicae and partial paniculate swallowwort root into fine powder, and screening for later use; adding water into the residual paniculate swallowwort root, infiltrating 1-3 hours, adding sodium chloride, distilling by using water vapor, cooling the distillate, crystallizing, filtering, and crystallizing, thereby obtaining paeonol for later use; adding water into alangium platanifolium for decocting, adding the decoction dregs of the paniculate swallowwort root, adding water with liquorice for decocting, filtering the decoction, taking the filtrate for later use, decocting the decoction dregs for 1-2 times, filtering, mixing the filtrate, concentrating to a proper amount, adding the radix angelicae and paniculate swallowwort root powder, uniformly mixing, drying, grinding into fine powder, adding a proper amount of auxiliary materials, preparing the granules, and drying; and adding a paeonol ethanol solution or a paeonol inclusion compound, uniformly mixing, tabletting into 100 tablets, and performing sugar coating, thereby obtaining the products.
Description
Technical field
The invention belongs to field of medicaments, relate to a kind of preparation method of rheumatism stator.
Technical background
Rheumatism stator belongs to street drug, this medicine by Radix Alangii, the Radix Angelicae Dahuricae, Radix Cynanchi Paniculati, Radix Glycyrrhizae four kinds of Chinese crude drugs through being processed into tablet.There is the dehumidifying of loose wind, removing obstruction in the collateral to relieve pain.Sick for the numbness caused by rheumatism resistance network, disease sees arthralgia; Rheumatic arthritis, rheumatoid arthritis, rib neuralgia, sciatica is shown in above-mentioned patient, and clinical efficacy is remarkable, is widely used.
Due in rheumatism stator, crude drug Radix Alangii must shape root (Radix Alangii) toxicity comparatively large, poisoning the lighter has giddy, unable, and severe one can be lethal because of respiration inhibition.First will consider to do artificial respiration in rescue, other symptomatic treatments also need in time.When doing muscle relaxant use, more should carry out having the hospital of rescue condition.These species are the poisonous plants that Chinese Plants spectrum data storehouse is included, and its toxicity is that root is poisonous, and fibrous root is the most malicious.Record in supplementary Amplifications of the Compendium of Materia Medica: " wood anistree (Radix Alangii) is hot in nature, power is violent, poisonous ... though sturdy people also should use less ".Venoterpine (venoterpine) and racemization poison multitude's alkali (dl-anbasine) is got from the root of Radix Alangii drying, stem, branch, wherein containing β-Amyrin caproate (β-amyrin acetate), triacontanol (triacontanol), cupreol (β-sitosterol).Send out from the wooden dry root of melon, stem, branch and to obtain Fructus seu radix camptothecae acuminatae (Fructus Camptothecae Acuminatae) subsidy alkali (venoterpine) and racemization poison multitude's alkali (dl-anabasine) 2 kinds of alkaloids.
The fibrous root of Radix Alangii and root bark are containing alkaloid, phenols, aminoacid, organic acid, resin.Fibrous root, mainly containing alkaloid and glucoside, contains cardiotonic glycoside again.Subacute toxicity: to intravenous rabbit injection Radix Alangii total alkaloids 1.9mg/kg, or with fibrous root decoct 10g/kg gastric infusion, connect to 15 days, after the medication of result gavage group most animals, B.S.P. retention rate raises, and has certain influence to liver function.The slight focal inflammation of animal kidney of intravenously administrable group, all has the degeneration of liver mild fatty in two treated animals, or mild inflammation, or has focal necrosis.That is, if contained alkaloidal too high levels in medicine, will Drug safety be reduced, increase toxic and side effects.
The method that Chinese Pharmacopoeia 2010 editions discloses rheumatism stator and prepares: the Radix Angelicae Dahuricae and Radix Cynanchi Paniculati 15g are ground into fine powder, sieve.Remaining Radix Cynanchi Paniculati adds water, and infiltrates 2 hours, vapor distillation 6 hours, and distillate cools, crystallize, and filter, crystallization (paeonol) is for subsequent use; Medicinal residues and Radix Alangii, Radix Glycyrrhizae decoct with water secondary, each 2 hours, and decocting liquid filters, filtrate merging is concentrated into appropriate, mixes with above-mentioned powder, dry, be ground into fine powder, add right amount of auxiliary materials, granule processed, dry, add paeonol (dissolving by ethanol in proper amount), mixing, is pressed into 1000, sugar coating, to obtain final product.
Chinese patent (CN102579514) discloses the concocting method of Radix Alangii: 1) get Radix Alangii medical material, select, and is cut into long section, and length is no more than 15cm; 2) Sucus Glycyrrhizae is prepared: according to 1000 parts of clean medical materials of Radix Alangii, the ratio of 200 portions of Radix Glycyrrhizaes, takes Radix Glycyrrhizae.The Radix Glycyrrhizae weighed up is decocted 2 times, adds 10 times of water gagings at every turn, first time decocts 2h, and second time decocts 1h, and filter after decocting, filtrate is for subsequent use; 3) according to 1000 parts of clean medical materials of Radix Alangii, the ratio of 500 portions of milk, adds milk in the above-mentioned Sucus Glycyrrhizae prepared, and adds the Radix Alangii medical material after above-mentioned cutting, adds water and supplies the volume of clean medical material 14 times amount, decocts 2h, filters.4) by the forced air drying at 45 DEG C ± 2 DEG C of Radix Alangii after boiling, to obtain final product.
Some Radix Alangiis are also had to take to extract with acid extraction and ethanol, the present invention adopts water extraction, by the time of extraction is different with order and decoction method is different, in Radix Alangii, alkaloid reduces significantly, obtain unexpected effect, paeonol takes clathrate to add, and stability improves preferably.
Just based on above reason, inventor has done improvement to existing preparation method.Rheumatism stator is made up of Radix Alangii, the Radix Angelicae Dahuricae, Radix Cynanchi Paniculati, Radix Glycyrrhizae four kinds of crude drug, wherein in Radix Alangii, contained alkaloidal content is the highest, therefore, when ensureing curative effect of medication, how reducing alkaloidal content in Radix Alangii is the direction that the present invention mainly studies.The present invention, by the improvement to preparation method, effectively improves Drug safety and stability, reduces the incidence rate of untoward reaction.
Summary of the invention
The object of the invention is to provide that a kind of safety is high, the rheumatism stator of few side effects, good stability.
The present invention, by improving extracting method, effectively reduces the content of total alkaloids in medicine.Meanwhile, by beta-cyclodextrin inclusion compound paeonol, the stability of rheumatism stator can be significantly improved.
Detailed, technical solution of the present invention is as follows:
Rheumatism stator of the present invention, is prepared by following methods:
Radix Alangii 1500g Radix Angelicae Dahuricae 50g Radix Cynanchi Paniculati 150g Radix Glycyrrhizae 20g
Preparation process is as follows:
(1) first get the 50g Radix Angelicae Dahuricae and 15g Radix Cynanchi Paniculati is ground into fine powder, sieve for subsequent use;
(2) get remaining 135g Radix Cynanchi Paniculati to add water, infiltrate 1-3 hour, add the sodium chloride of the amount 4-9% of medical material, with vapor distillation 3-9 hour, distillate cools, crystallize, and filter, crystallization, obtains paeonol, for subsequent use;
(3) after 1500g Radix Alangii being decocted with water 1-2 hour, add Radix Cynanchi Paniculati medicinal residues and decoct with water 1-3 hour together with 20g Radix Glycyrrhizae, decocting liquid filters, filtrate is for subsequent use, and medicinal residues decoct 1-2 time again, and the time is 1-3 hour, filter, filtrate merging is concentrated into appropriate, adds the Radix Angelicae Dahuricae and the mixing of Radix Cynanchi Paniculati powder, dry, be ground into fine powder, add right amount of auxiliary materials, granule processed, dry;
(4) add paeonol alcoholic solution or paeonol inclusion compound subsequently, mixing, is pressed into 1000, sugar coating, obtains final product.
Wherein, crystal described in step 2 is paeonol,
Wherein, step 3, Radix Alangii and Radix Glycyrrhizae are that successively order is extracted, after first Radix Alangii being decocted with water 1 hour, decoct with water 1-3 hour adding Radix Cynanchi Paniculati medicinal residues together with Radix Glycyrrhizae, decocting liquid filters, filtrate is for subsequent use, and medicinal residues decoct 1-3h again, and filtrate merging is concentrated into appropriate, add the powder of step (1), mixing, dry, be ground into fine powder, add right amount of auxiliary materials, granule processed, dry
Wherein, paeonol alcoholic solution described in step 4, refers to: paeonol 95% dissolve with ethanol, forms solution.Be preferably, paeonol: ethanol=1:3 (W/V).
The preparation process of paeonol inclusion compound: get beta-schardinger dextrin-100 parts and add appropriate water, is adding paeonol alcoholic solution 10 parts, stirring and dissolving, employing colloid mill grinds, and is cooled to-1 ~ 15 DEG C, filters, obtain solids, 30 ~ 40 DEG C of dryings, obtain paeonol inclusion compound.
Preferably, preparation method of the present invention, comprises the following steps:
Get the 50g Radix Angelicae Dahuricae and 15g Radix Cynanchi Paniculati is ground into fine powder, sieve for subsequent use; Get remaining 135g Radix Cynanchi Paniculati to add water, add the sodium chloride of the amount 4-9% of medical material, infiltrate 2 hours, vapor distillation 6 hours, distillate cools, crystallize, and filter, crystallization obtains paeonol, for subsequent use; After 1500g Radix Alangii is decocted with water 1 hour, add Radix Cynanchi Paniculati medicinal residues and decoct with water 2 hours together with 20g Radix Glycyrrhizae, decocting liquid filters, filtrate is for subsequent use, and medicinal residues decoct 2h again, filters, filtrate merging is concentrated into appropriate, adds the Radix Angelicae Dahuricae and the mixing of Radix Cynanchi Paniculati powder, dry, be ground into fine powder, add right amount of auxiliary materials, granule processed, drying, adds paeonol alcoholic solution or paeonol inclusion compound, mixing, be pressed into 1000, sugar coating, obtain final product.
Preferred further, preparation method of the present invention,
Get the 50g Radix Angelicae Dahuricae and 15g Radix Cynanchi Paniculati is ground into fine powder, sieve for subsequent use; Get remaining 135g Radix Cynanchi Paniculati to add water, add the sodium chloride of the amount 4-9% of medical material, infiltrate 2 hours, vapor distillation 6 hours, distillate cools, crystallize, and filter, crystallization obtains paeonol, obtains Aromatic water for subsequent use simultaneously;
After 1500g Radix Alangii is decocted with water 1 hour, add Radix Cynanchi Paniculati medicinal residues and decoct with water 2 hours together with 20g Radix Glycyrrhizae, decocting liquid filters, and filtrate is for subsequent use, medicinal residues decoct 2h again, filter, and filtrate merging is concentrated into appropriate, add the Radix Angelicae Dahuricae and the mixing of Radix Cynanchi Paniculati powder, dry, be ground into fine powder, add right amount of auxiliary materials, granule processed, dry, add paeonol inclusion compound, mixing, is pressed into 1000, sugar coating, to obtain final product
The preparation of paeonol inclusion compound: salvianolic acid is dissolved in the ethanol of 3 times amount (V/W), add 14.3 times (W/W) in the beta-schardinger dextrin-of paeonol, add 45 times (V/W) in the Aromatic water of beta-schardinger dextrin-, 4 hours are ground with colloid mill, be cooled to-1 DEG C, filter, obtain solids, cold drying obtains clathrate.
The present invention is also to the rheumatism stator that said method prepares, and carry out total alkaloid content detection, process is as follows:
Total alkaloids is limited the quantity: get this product 20, removing sugar-coat, accurately weighed, porphyrize, accurate absorption fine powder appropriate (about 10 weights), put in apparatus,Soxhlet's, add methanol-strong ammonia solution (95:5) mixed solution appropriate, heating and refluxing extraction is to closely colourless, volatilize methanol, residue 3% sulfuric acid solution 10ml dissolves, use 3% sulfuric acid solution 10ml again, gradation washing container, washing liquid is incorporated in acid solution, add chloroform jolting and extract 2 times, each 20ml, merge chloroform liquid, extract with 3% sulfuric acid solution 10ml jolting, discard chloroform liquid, the acid solution that merging front and back are twice, add strong ammonia solution and regulate pH value to 9 ~ 10, 4 times are extracted again with chloroform jolting, each 10ml, merge chloroform liquid, by being covered with the funnel of anhydrous sodium sulfate 1g, filter, filtrate is placed in the evaporating dish that 105 DEG C are dried to constant weight, evaporate to dryness in water-bath, residue is dried to constant weight at 105 DEG C, calculate, obtain.The every sheet of this product must not cross 1.2mg containing total alkaloids.
The present invention, in order to reduce the content of total alkaloids in medicine, reduces the toxic and side effects of medicine, carries out a large amount of screenings to preparation method:
Experiment 1, preparation method screening
1, solvent screening
The 50g Radix Angelicae Dahuricae and Radix Cynanchi Paniculati 15g are ground into fine powder, sieve.135g Radix Cynanchi Paniculati adds water, and infiltrates 2 hours, vapor distillation 6 hours, and distillate cools, crystallize, and filter, crystallization (paeonol) is for subsequent use; Medicinal residues and 1500g Radix Alangii, 20g Radix Glycyrrhizae solubilizer extract secondary, each 2 hours, and decocting liquid filters, and filtrate merging is concentrated into appropriate.
Table 1, employing different solvents extract the content of gained total alkaloids
| Different solvents | Obtain cream amount | Relative density | Total alkaloids/mg |
| 70% ethanol | 580 | 1.25 | 1350 |
| 2% aqueous hydrochloric acid solution | 612 | 1.25 | 1089 |
| Water | 560 | 1.25 | 980 |
Experimental result shows, and select ethonal extraction, in extract, total alkaloid content is the highest, comparatively speaking, best by water extraction effect, content below the control 1000mg of total alkaloids.Therefore, preferred water is as Extraction solvent of the present invention.
2, the extraction of various combination mode
Formula of the present invention is made up of 4 kinds of crude drug, one skilled in the art will appreciate that Chinese medicine adopts usually and singly puies forward or close the mode put forward and extract.Conjunction is carried in process, and select different crude drug together to extract, its effect often there are differences.In order to better control the content of total alkaloids, we screen the extraction of various combination mode:
The 50g Radix Angelicae Dahuricae and Radix Cynanchi Paniculati 15g are ground into fine powder, sieve.135g Radix Cynanchi Paniculati adds water, and infiltrates 2 hours, vapor distillation 6 hours, and distillate cools, crystallize, and filter, crystallization (paeonol) is for subsequent use; Extracting mode is in Table-2, and decocting liquid filters, and filtrate merging is concentrated into appropriate.
Table 2, different modes extract
| Various combination mode | Decocting time/h | Total alkaloids |
| Radix Cynanchi Paniculati and Radix Alangii | 2 | 1000 |
| Radix Alangii and Radix Glycyrrhizae | 2 | 930 |
Experimental result shows, and Radix Alangii and Radix Glycyrrhizae are closed and carry, and effectively can reduce the content of total alkaloids.
3, sodium chloride is investigated on the impact of extracting
Scheme 1,135g Radix Cynanchi Paniculati add water, and infiltrate 2 hours, vapor distillation 6 hours, and distillate cools, crystallize, and filter, crystallization (paeonol) is for subsequent use;
Scheme 2,135g Radix Cynanchi Paniculati add water, and add the sodium chloride of the amount 4-9% of medical material, infiltrate 2 hours, vapor distillation 6 hours, and distillate cools, crystallize, and filter, crystallization (paeonol) is for subsequent use;
Table 3, different modes extract
| Different schemes | Paeonol total amount |
| Scheme 1 | 1.5g |
| Scheme 2 | 2.1g |
Therefore the precipitation that sodium chloride contributes to paeonol is added.
4, extracting mode and sequentially screening
Find in experiment 2, Radix Alangii and Radix Glycyrrhizae close that to put forward effect better.Conjunction is carried and is divided into and first singly carries respectively, by single extract united extraction; Also be divided into and first singly carry a kind of medicine, close together and carry adding all the other medicines.The present invention also investigates further to this.
Scheme 1, Radix Alangii first decocts extraction 1 hour, then adds Radix Glycyrrhizae and Radix Cynanchi Paniculati medicinal residues and decoct extraction 2 hours;
Scheme 2: extract 3 hours after Radix Alangii, Radix Glycyrrhizae and the mixing of Radix Cynanchi Paniculati medicinal residues.
Table 4,
| Various combination mode | Decocting time/h | Decocting time/h | Total alkaloids |
| Radix Alangii | 1 | Add Radix Glycyrrhizae and Radix Cynanchi Paniculati medicinal residues extract 2 hours | 870 |
| Radix Alangii and Radix Glycyrrhizae and medicinal residues | 2 | 1 | 920 |
Experimental result shows, and adopt the extracting method of scheme 1, acquired effect is best, effectively can make a price reduction the content of total alkaloids.
Through above-mentioned preferably a series of, obtain the most preferred preparation method of the present invention:
Get the 50g Radix Angelicae Dahuricae and 15g Radix Cynanchi Paniculati is ground into fine powder, sieve for subsequent use; Get remaining 135g Radix Cynanchi Paniculati to add water, infiltrate 2 hours, add the sodium chloride of the amount 4-9% of medical material, vapor distillation 6 hours, distillate cools, crystallize, and filter, filtrate is that Aromatic water is for subsequent use, and crystallization, obtains paeonol, for subsequent use; After 1500g Radix Alangii is decocted with water 1 hour, add Radix Cynanchi Paniculati medicinal residues and decoct with water 2 hours together with 20g Radix Glycyrrhizae, decocting liquid filters, and filtrate is for subsequent use, medicinal residues decoct 1 time again, and the time is 2h, filter, filtrate merging is concentrated into appropriate, adds the Radix Angelicae Dahuricae and the mixing of Radix Cynanchi Paniculati powder, dry, be ground into fine powder, add right amount of auxiliary materials, granule processed, drying, adds paeonol alcoholic solution or paeonol inclusion compound, mixing, be pressed into 1000, sugar coating, obtain final product.
Experiment 2, inclusion technique screening
The present invention, in order to improve the stability of paeonol in rheumatism stator, carries out enclose with beta-schardinger dextrin-to it.
Current rheumatism stator granule adopts and adds paeonol (dissolving by ethanol in proper amount), tabletting, and sugar coating, to obtain final product.
Because paeonol easily volatilizees, qualitative identification and assay instability, usually directly have influence on clinical efficacy, therefore in order to ensure the stability of paeonol, the present invention adopts beta-cyclodextrin inclusion compound paeonol.
Its preferred process is as follows:
Get beta-schardinger dextrin-and be added to the water dissolving, adding paeonol alcoholic solution, stirring and dissolving, with colloid mill grinding, be cooled to-1 ~ 15 DEG C, filter, obtain solids 30 ~ 40 DEG C of dryings, obtain paeonol inclusion compound.
The screening of table 5, enclose process
| Clathrate 1 | Clathrate 2 | Clathrate 3 | Clathrate 4 | Clathrate 5 | Clathrate 6 |
| Beta-schardinger dextrin-(g) | 100 | 100 | 100 | 100 | 100 | 100 |
| Water (ml) | 3500 | 4000 | 4000 | 4500 | 4500 | 5000 |
| Paeonol (g) | 5 | 6 | 6 | 7 | 7 | 8 |
| Temperature (DEG C) | -1 | -1 | -1 | -1 | -1 | -1 |
| Ethanol (ml) | 15 | 18 | 18 | 21 | 21 | 24 |
| The time (h) of colloid mill mill | 2 | 2 | 4 | 2 | 4 | 4 |
| Envelop rate (%) | 66 | 65 | 66 | 62 | 68 | 56 |
According to the balance of material and reasonably apply, by comparing discovery, clathrate 5 is the most reasonable.
Investigate the stability of clathrate and non-clathrate
Paeonol method for measuring:
[assay] measures according to high performance liquid chromatography (annex VI D).
Chromatographic condition and system suitability take octadecylsilane chemically bonded silica as filler; With acetonitrile-water (38:26) for mobile phase; Determined wavelength is 274nm.Number of theoretical plate calculates should be not less than 4000 by paeonol peak.
The preparation of reference substance solution gets paeonol reference substance in right amount, accurately weighed, adds methanol and makes the solution of every 1ml containing 20 μ g, to obtain final product.
This product 10 is got in the preparation of need testing solution, removing sugar-coat, accurately weighed, porphyrize, accurate fine powder of drawing is about 0.15g, puts in 50ml measuring bottle, add the appropriate supersound process of methanol (power 250W, frequency 33kHz) 30 minutes, let cool, add methanol dilution to scale, shake up, filter, get subsequent filtrate, to obtain final product.
Algoscopy is accurate respectively draws reference substance solution and each 10 μ l of need testing solution, injection liquid chromatography, measures, to obtain final product.
The experimental group 1:50g Radix Angelicae Dahuricae and Radix Cynanchi Paniculati 15g are ground into fine powder, sieve.135g Radix Cynanchi Paniculati adds water, and infiltrates 2 hours, vapor distillation 6 hours, and distillate cools, crystallize, and filter, crystallization (paeonol) is for subsequent use; Radix Alangii 1500g decocts with water 1 hour, and medicinal residues and 20g Radix Glycyrrhizae decoct with water 2 hours, and decocting liquid filters, medicinal residues decoct once again, and filtrate merging is concentrated into appropriate, mixes with above-mentioned powder, drying, is ground into fine powder, adds right amount of auxiliary materials, granule processed, dry, add paeonol (dissolving by ethanol in proper amount), mixing, be pressed into 1000, sugar coating, obtain final product.
The experimental group 2:50g Radix Angelicae Dahuricae and Radix Cynanchi Paniculati 15g are ground into fine powder, sieve.135g Radix Cynanchi Paniculati adds water, and adds the sodium chloride of the amount 4-9% of medical material, infiltrates 2 hours, vapor distillation 6 hours, and distillate cools, crystallize, and filter, crystallization (paeonol) is for subsequent use; Radix Alangii 1500g decocts with water 1 hour, is adding Radix Cynanchi Paniculati medicinal residues and 20g Radix Glycyrrhizae decocts with water 2 hours, and decocting liquid filters, medicinal residues decoct once again, and filtrate merging is concentrated into appropriate, mixes with above-mentioned powder, drying, is ground into fine powder, adds right amount of auxiliary materials, granule processed, dry, add clathrate 5, mixing, be pressed into 1000, sugar coating, obtain final product.
The table 6 rheumatism stator paeonol accelerated stability of 6 months is investigated
Experimental result shows: after paeonol is made clathrate, its stability is increased dramatically, than the tabletting better effects if directly with paeonol.
Experiment 3, total alkaloid content are compared
Experimental group: select rheumatism stator prepared by the embodiment of the present invention 1.
Matched group: commercially available rheumatism stator.
Detection method: get this product 20, removing sugar-coat, accurately weighed, porphyrize, accurate absorption fine powder appropriate (about 10 weights), put in apparatus,Soxhlet's, add methanol-strong ammonia solution (95:5) mixed solution appropriate, heating and refluxing extraction is to closely colourless, volatilize methanol, residue 3% sulfuric acid solution 10ml dissolves, use 3% sulfuric acid solution 10ml again, gradation washing container, washing liquid is incorporated in acid solution, add chloroform jolting and extract 2 times, each 20ml, merge chloroform liquid, extract with 3% sulfuric acid solution 10ml jolting, discard chloroform liquid, the acid solution that merging front and back are twice, add strong ammonia solution and regulate pH value to 9 ~ 10, 4 times are extracted again with chloroform jolting, each 10ml, merge chloroform liquid, by being covered with the funnel of anhydrous sodium sulfate 1g, filter, filtrate is placed in the evaporating dish that 105 DEG C are dried to constant weight, evaporate to dryness in water-bath, residue is dried to constant weight at 105 DEG C, calculate, obtain.
Table 7, total alkaloid content compare
| Total alkaloid content in every sheet rheumatism stator | |
| Experimental group | 0.6mg |
| Matched group | 1.0mg |
Experimental result shows, and rheumatism stator of the present invention is relative to commercially available rheumatism stator, and its alkaloid is less, and drug safety is higher.
The present invention, by the adjustment to preparation method, effectively improves the safety and stability of medicine, reduces toxic and side effects.Preparation technology of the present invention is simple, and require low to operating environment, cost is low, is applicable to large-scale production.
Detailed description of the invention
By following examples, the present invention is further illustrated, but not as restriction.
Embodiment 1
The 50g Radix Angelicae Dahuricae and Radix Cynanchi Paniculati 15g are ground into fine powder, sieve for subsequent use; Get 135g Radix Cynanchi Paniculati to add water, add the sodium chloride of the amount 4-9% of medical material, infiltrate 2 hours, vapor distillation 6 hours, distillate cools, crystallize, and filter, crystallization obtains paeonol, obtains Aromatic water for subsequent use simultaneously;
Get paeonol to join (paeonol: proportion of ethanol is 1g:3ml) in ethanol and obtain paeonol alcoholic solution, add 14.3 times of beta-schardinger dextrin-s to paeonol (paeonol: beta-schardinger dextrin-ratio is 1g:14.3g) in the solution, add 45 times of Aromatic water to beta-schardinger dextrin-(Aromatic water: beta-schardinger dextrin-ratio is 45g:1g), 4 hours are ground with colloid mill, be cooled to-1 DEG C, filter, obtain solids, cold drying obtains paeonol inclusion compound;
Radix Alangii 1500g decocts with water 1 hour, and Radix Cynanchi Paniculati medicinal residues and 20g Radix Glycyrrhizae decoct with water 2 hours, and decocting liquid filters, medicinal residues decoct once again, decoct 2 hours, and filtrate merging is concentrated into appropriate, mix with above-mentioned powder, dry, be ground into fine powder, add right amount of auxiliary materials, granule processed, dry, add paeonol inclusion compound, mixing, is pressed into 1000, sugar coating, to obtain final product.
Embodiment 2
The 50g Radix Angelicae Dahuricae and 15g Radix Cynanchi Paniculati are ground into fine powder, sieve, 135g Radix Cynanchi Paniculati adds water, add the sodium chloride of the amount 4-9% of medical material, infiltrate 2 hours, vapor distillation 6 hours, distillate cools, crystallize, filter, obtain crystallization (paeonol), medicinal residues and 1500g Radix Alangii, 20g Radix Glycyrrhizae decocts with water secondary, each 2 hours, decocting liquid filters, filtrate merging is concentrated into appropriate, mix with above-mentioned powder, dry, be ground into fine powder, add right amount of auxiliary materials, granule processed, dry, add paeonol (dissolving by ethanol in proper amount), mixing, be pressed into 1000, sugar coating, obtain.
Embodiment 3
The 50g Radix Angelicae Dahuricae and Radix Cynanchi Paniculati 15g are ground into fine powder, sieve for subsequent use; Get 135g Radix Cynanchi Paniculati to add water, add the sodium chloride of the amount 4-9% of medical material, infiltrate 1 hour, vapor distillation 3 hours, distillate cools, crystallize, filters, obtains crystallization (paeonol), obtain Aromatic water for subsequent use simultaneously; Paeonol adds dissolving (paeonol: proportion of ethanol is 1g:3ml) in the ethanol of 3 times amount, adding 14.3 times of beta-schardinger dextrin-s to paeonol (paeonol: beta-schardinger dextrin-ratio is 1g:14.3g), add 45 times to the Aromatic water of beta-schardinger dextrin-, (Aromatic water: beta-schardinger dextrin-ratio is 45g:1g) grinds 4 hours with colloid mill, be cooled to-1 DEG C, filter, obtain solids, cold drying obtains clathrate.
Radix Alangii 1500g decocts with water 1 hour, and Radix Cynanchi Paniculati medicinal residues and 20g Radix Glycyrrhizae decoct with water 1 hour, and decocting liquid filters, medicinal residues decoct once again, decoct 2 hours, and filtrate merging is concentrated into appropriate, mix with above-mentioned powder, dry, be ground into fine powder, add right amount of auxiliary materials, granule processed, dry, add paeonol inclusion compound (being converted to paeonol 1.8g), mixing, is pressed into 1000, sugar coating, to obtain final product.
Embodiment 4
The 50g Radix Angelicae Dahuricae and Radix Cynanchi Paniculati 15g are ground into fine powder, sieve for subsequent use; Get 135g Radix Cynanchi Paniculati to add water, add the sodium chloride of the amount 4-9% of medical material, infiltrate 3 hours, vapor distillation 9 hours, distillate cools, crystallize, filters, obtains crystallization (paeonol), obtain Aromatic water for subsequent use simultaneously; Paeonol adds dissolving (paeonol: proportion of ethanol is 1g:3ml) in the ethanol of 3 times amount, adding 14.3 times of beta-schardinger dextrin-s to paeonol (paeonol: beta-schardinger dextrin-ratio is 1g:14.3g), add 45 times of Aromatic water to beta-schardinger dextrin-(Aromatic water: beta-schardinger dextrin-ratio is 45g:1g), 4 hours are ground with colloid mill, be cooled to-1 DEG C, filter, obtain solids, cold drying obtains clathrate.
Radix Alangii 1500g decocts with water 1 hour, and Radix Cynanchi Paniculati medicinal residues and 20g Radix Glycyrrhizae decoct with water 2 hours, and decocting liquid filters, medicinal residues decoct once again, decoct 2 hours, and filtrate merging is concentrated into appropriate, mix with above-mentioned powder, dry, be ground into fine powder, add right amount of auxiliary materials, granule processed, dry, add paeonol inclusion compound, mixing, is pressed into 1000, sugar coating, to obtain final product.
Embodiment 5
The assay of paeonol is as follows: chromatographic condition and system suitability take octadecylsilane chemically bonded silica as filler; With acetonitrile-water (38:26) for mobile phase; Determined wavelength is 274nm.Number of theoretical plate calculates should be not less than 4000 by paeonol peak.
The preparation of reference substance solution gets paeonol reference substance in right amount, accurately weighed, adds methanol and makes the solution of every 1ml containing 20 μ g, to obtain final product.
The crystal 15mg of step 2 of the present invention is got in the preparation of need testing solution, accurately weighed, adds methanol and makes the solution of every 1ml containing 20 μ g, to obtain final product.
Algoscopy is accurate respectively draws reference substance solution and each 10 μ l of need testing solution, injection liquid chromatography, measures, to obtain final product.
Crystal is in paeonol (C9H10O3), and content must not be less than 95%.
Claims (6)
1. a preparation method for rheumatism stator, be processed into by following crude drug:
Radix Alangii 1500g Radix Angelicae Dahuricae 50g Radix Cynanchi Paniculati 150g Radix Glycyrrhizae 20g
Preparation process is as follows:
(1) first get the 50g Radix Angelicae Dahuricae and 15g Radix Cynanchi Paniculati is ground into fine powder, sieve for subsequent use;
(2) get remaining 135g Radix Cynanchi Paniculati to add water, infiltrate 1-3 hour, with vapor distillation 3-9 hour, distillate cools, crystallize, and filter, crystallization, obtains paeonol, for subsequent use;
(3) medicinal residues of Radix Cynanchi Paniculati and 1500g Radix Alangii, 20g Radix Glycyrrhizae are decocted with water 1-3 time, each 1-3 hour, decocting liquid filters, and filtrate merging is concentrated into appropriate, mixes with above-mentioned powder, dry, is ground into fine powder, adds right amount of auxiliary materials, granule processed, dry;
(4) add paeonol alcoholic solution or paeonol inclusion compound subsequently, mixing, is pressed into 1000, sugar coating, obtains final product.
2. preparation method according to claim 1, is characterized in that, step 3, Radix Alangii and Radix Glycyrrhizae are that successively order is extracted, and after first Radix Alangii being decocted with water 1 hour, add Radix Cynanchi Paniculati medicinal residues and decoct with water 1-3 hour together with Radix Glycyrrhizae, decocting liquid filters, and filtrate is for subsequent use, and medicinal residues decoct 1-3h again, filtrate merging is concentrated into appropriate, adds the powder of step (1), mixing, drying, is ground into fine powder, adds right amount of auxiliary materials, granule processed, dry.
3. preparation method according to claim 1, is characterized in that, paeonol alcoholic solution described in step 4, refers to: paeonol 95% dissolve with ethanol, forms solution.Be preferably, paeonol: ethanol=1:3 (W/V).
4. preparation method according to claim 1, it is characterized in that, the preparation process of paeonol inclusion compound described in step 4: get beta-schardinger dextrin-100 parts and add appropriate water, is adding paeonol alcoholic solution 10 parts, stirring and dissolving, employing colloid mill grinds, be cooled to-1 ~ 15 DEG C, filter, obtain solids, 30 ~ 40 DEG C of dryings, obtain paeonol inclusion compound.
5. preparation method according to claim 1, is characterized in that, step is as follows:
Get the 50g Radix Angelicae Dahuricae and 15g Radix Cynanchi Paniculati is ground into fine powder, sieve for subsequent use; Get remaining 135g Radix Cynanchi Paniculati to add water, add the sodium chloride of the amount 4-9% of medical material, infiltrate 2 hours, vapor distillation 6 hours, distillate cools, crystallize, and filter, crystallization obtains paeonol, for subsequent use; After 1500g Radix Alangii is decocted with water 1 hour, add Radix Cynanchi Paniculati medicinal residues and decoct with water 2 hours together with 20g Radix Glycyrrhizae, decocting liquid filters, filtrate is for subsequent use, and medicinal residues decoct 2h again, filters, filtrate merging is concentrated into appropriate, adds the Radix Angelicae Dahuricae and the mixing of Radix Cynanchi Paniculati powder, dry, be ground into fine powder, add right amount of auxiliary materials, granule processed, drying, adds paeonol alcoholic solution or paeonol inclusion compound, mixing, be pressed into 1000, sugar coating, obtain final product.
6. preparation method according to claim 1, is characterized in that, step is as follows:
Get the 50g Radix Angelicae Dahuricae and 15g Radix Cynanchi Paniculati is ground into fine powder, sieve for subsequent use; Get remaining 135g Radix Cynanchi Paniculati to add water, add the sodium chloride of the amount 4-9% of medical material, infiltrate 2 hours, vapor distillation 6 hours, distillate cools, crystallize, and filter, crystallization obtains paeonol, obtains Aromatic water for subsequent use simultaneously;
After 1500g Radix Alangii is decocted with water 1 hour, add Radix Cynanchi Paniculati medicinal residues and decoct with water 2 hours together with 20g Radix Glycyrrhizae, decocting liquid filters, and filtrate is for subsequent use, medicinal residues decoct 2h again, filter, and filtrate merging is concentrated into appropriate, add the Radix Angelicae Dahuricae and the mixing of Radix Cynanchi Paniculati powder, dry, be ground into fine powder, add right amount of auxiliary materials, granule processed, dry, add paeonol inclusion compound, mixing, is pressed into 1000, sugar coating, to obtain final product
The preparation of paeonol inclusion compound: salvianolic acid is dissolved in the ethanol of 3 times amount (V/W), add 14.3 times (W/W) in the beta-schardinger dextrin-of paeonol, add 45 times (V/W) in the Aromatic water of beta-schardinger dextrin-, 4 hours are ground with colloid mill, be cooled to-1 DEG C, filter, obtain solids, cold drying obtains clathrate.
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| 倪健: "《200种中药片剂制备关键技术》", 30 November 2007, 化学工业出版社 * |
| 国家药典委员会编: "《中华人民共和国药典 2010年版 1部》", 31 January 2010, 中国医药科技出版社 * |
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