CN104490990B - A kind of preparation method of rheumatism stator - Google Patents
A kind of preparation method of rheumatism stator Download PDFInfo
- Publication number
- CN104490990B CN104490990B CN201410834244.XA CN201410834244A CN104490990B CN 104490990 B CN104490990 B CN 104490990B CN 201410834244 A CN201410834244 A CN 201410834244A CN 104490990 B CN104490990 B CN 104490990B
- Authority
- CN
- China
- Prior art keywords
- added
- paeonol
- hours
- ground
- paniculate
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- UILPJVPSNHJFIK-UHFFFAOYSA-N Paeonol Chemical compound COC1=CC=C(C(C)=O)C(O)=C1 UILPJVPSNHJFIK-UHFFFAOYSA-N 0.000 claims abstract description 146
- YLTGFGDODHXMFB-UHFFFAOYSA-N isoacetovanillon Natural products COC1=CC=C(C(C)=O)C=C1O YLTGFGDODHXMFB-UHFFFAOYSA-N 0.000 claims abstract description 73
- MLIBGOFSXXWRIY-UHFFFAOYSA-N paeonol Natural products COC1=CC=C(O)C(C(C)=O)=C1 MLIBGOFSXXWRIY-UHFFFAOYSA-N 0.000 claims abstract description 73
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 55
- 239000000843 powder Substances 0.000 claims abstract description 49
- 241000759271 Alangium Species 0.000 claims abstract description 43
- 238000001914 filtration Methods 0.000 claims abstract description 43
- 241001233914 Chelidonium majus Species 0.000 claims abstract description 37
- 239000000463 material Substances 0.000 claims abstract description 33
- 239000007788 liquid Substances 0.000 claims abstract description 32
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 30
- 238000002425 crystallisation Methods 0.000 claims abstract description 29
- 230000008025 crystallization Effects 0.000 claims abstract description 29
- 239000000706 filtrate Substances 0.000 claims abstract description 28
- 238000002156 mixing Methods 0.000 claims abstract description 27
- 235000001287 Guettarda speciosa Nutrition 0.000 claims abstract description 26
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- 238000001816 cooling Methods 0.000 claims abstract description 18
- 238000001256 steam distillation Methods 0.000 claims abstract description 18
- 239000011780 sodium chloride Substances 0.000 claims abstract description 15
- 239000008188 pellet Substances 0.000 claims abstract description 14
- 238000009495 sugar coating Methods 0.000 claims abstract description 13
- 241000125175 Angelica Species 0.000 claims description 24
- 235000019441 ethanol Nutrition 0.000 claims description 24
- 241000512000 Asclepias curassavica Species 0.000 claims description 23
- 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 claims description 21
- 229920000858 Cyclodextrin Polymers 0.000 claims description 20
- 239000001116 FEMA 4028 Substances 0.000 claims description 19
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 19
- 229960004853 betadex Drugs 0.000 claims description 19
- 241000202807 Glycyrrhiza Species 0.000 claims description 13
- 239000000084 colloidal system Substances 0.000 claims description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 240000005001 Paeonia suffruticosa Species 0.000 claims description 6
- 235000003889 Paeonia suffruticosa Nutrition 0.000 claims description 6
- 239000003814 drug Substances 0.000 abstract description 18
- -1 infiltrates 13 hours Substances 0.000 abstract description 2
- 244000061520 Angelica archangelica Species 0.000 abstract 2
- 229930013930 alkaloid Natural products 0.000 description 26
- 150000003797 alkaloid derivatives Chemical class 0.000 description 25
- 239000000243 solution Substances 0.000 description 24
- 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
- 238000000605 extraction Methods 0.000 description 18
- 238000000034 method Methods 0.000 description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- 229940079593 drug Drugs 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 239000013558 reference substance Substances 0.000 description 6
- 231100000331 toxic Toxicity 0.000 description 6
- 230000002588 toxic effect Effects 0.000 description 6
- 238000012216 screening Methods 0.000 description 5
- 238000007873 sieving Methods 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
- 238000001514 detection method Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000012085 test solution Substances 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
- 239000003513 alkali Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 229940125898 compound 5 Drugs 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 231100000614 poison Toxicity 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 206010013786 Dry skin Diseases 0.000 description 2
- 241000196324 Embryophyta Species 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
- 241001465754 Metazoa Species 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
- 206010044565 Tremor Diseases 0.000 description 2
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 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
- 235000019425 dextrin Nutrition 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
- 239000006210 lotion Substances 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
- 239000002245 particle Substances 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
- 238000003756 stirring Methods 0.000 description 2
- 239000002023 wood Substances 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 244000241257 Cucumis melo Species 0.000 description 1
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 description 1
- 241000825107 Hierochloe Species 0.000 description 1
- 235000015466 Hierochloe odorata Nutrition 0.000 description 1
- 208000004044 Hypesthesia Diseases 0.000 description 1
- 240000007232 Illicium verum Species 0.000 description 1
- 235000008227 Illicium verum Nutrition 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
- 230000006838 adverse reaction Effects 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
- 150000001413 amino acids Chemical class 0.000 description 1
- 206010003246 arthritis Diseases 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
- 229940097217 cardiac glycoside Drugs 0.000 description 1
- 239000002368 cardiac glycoside Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 238000009472 formulation Methods 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
- 244000144993 groups of animals Species 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
- 208000034783 hypoesthesia Diseases 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration 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
- 208000018937 joint inflammation Diseases 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
- 239000000203 mixture 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
- 231100000862 numbness Toxicity 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 description 1
- 239000002304 perfume Substances 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
- 230000007096 poisonous 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
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- 239000002893 slag Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229930002534 steroid glycoside Natural products 0.000 description 1
- 239000002951 street drug Substances 0.000 description 1
- 231100000456 subacute toxicity Toxicity 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000003809 water extraction Methods 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 field of medicaments, are related to a kind of preparation method of rheumatism stator.Preparation method of the present invention, includes the following steps：It first takes the root of Dahurain angelica and part paniculate swallowwort to be ground into fine powder, sieves for subsequent use；It takes remaining paniculate swallowwort to add water, infiltrates 13 hours, sodium chloride is added, with steam distillation, distillate cooling, crystallization filters, and crystallization obtains Paeonol, spare；Alangium is added water to cook, the paniculate swallowwort dregs of a decoction are added and are added water to cook together with Radix Glycyrrhizae, decocting liquid filtration, filtrate is spare, and the dregs of a decoction decoct 12 times again, filtering, filtrate, which merges, is concentrated into appropriate, the addition root of Dahurain angelica and paniculate swallowwort powder mixing, dry, it is ground into fine powder, adds right amount of auxiliary materials, is made pellet, it is dry；Paeonol ethanol solution or paeonol inclusion compound, mixing is then added, is pressed into 1000, sugar coating to get.
Description
Technical field
The invention belongs to field of medicaments, are related to a kind of preparation method of rheumatism stator.
Technical background
Rheumatism stator belongs to street drug, and the medicine is by four kinds of alangium, the root of Dahurain angelica, paniculate swallowwort, Radix Glycyrrhizae processed systems of Chinese medicine
Piece agent.It dehumidifies, removes obstruction in channels to relieve pain with relieve heat.Numbness disease symptoms include the arthralgia caused by network are hindered for rheumatism；Rheumatism joint
Inflammation, rheumatoid arthritis, rib neuralgia, sciatica are shown in above-mentioned patient, and clinical efficacy is notable, is widely used.
Since in rheumatism stator, bulk pharmaceutical chemicals alangium must shape root (Radix Alangii) is more toxic, poisoning less serious case has dizzy, nothing
Power, severe one can be lethal because of respiration inhibition.It first has to consider to make artificial respiration in rescue, other symptomatic treatments also need in time.
Make muscle relaxant in use, should more be carried out in the hospital for having rescue condition.The species are that Chinese Plants spectrum data library is included
Poisonous plant, toxicity be root it is toxic, fibrous root is most malicious.《A Supplement to the Compendium of Materia Medica》Described in：" wood illiciumverum (alangium) property heat,
It is used though power is violent, toxic ... ... sturdy people is also preferably few ".Get venoterpine from the root, stem, branch that alangium is dried
(venoterpine) and racemization poison multitude alkali (dl-anbasine), wherein containing β-amyrin caproate (β-amyrin
Acetate), triacontanol (triacontanol), cupreol (β-sitosterol).Root, stem, the branch dried from melon wood
In send out to obtain camplotheca acuminata and subsidize alkali (venoterpine) and 2 kinds of alkaloids of racemization poison multitude alkali (dl-anabasine).
The fibrous root and root skin of alangium are containing alkaloid, phenols, amino acid, organic acid, resin.Fibrous root mainly contain alkaloid and
Glucoside, and contain cardiac glycoside.Subacute toxicity：Intravenous rabbit is given to inject alangium total alkaloid 1.9mg/kg, or with fibrous root decoction
10g/kg gastric infusions, even to 15 days, B.S.P. retention rates increase after as a result gavage group most animals medication, have one to liver function
Fixing is rung.The slight focal inflammation of animal kidney of intravenously administrable group has the denaturation of liver mild fatty in two groups of animals, or slight
Inflammation, or have focal necrosis.That is, if in drug contained alkaloid too high levels, it will reduce the safety of drug
Property, increase toxic side effect.
The method that Chinese Pharmacopoeia 2010 editions discloses the preparation of rheumatism stator：The root of Dahurain angelica and paniculate swallowwort 15g are ground into fine powder, mistake
Sieve.Remaining paniculate swallowwort adds water, infiltrates 2 hours, steam distillation 6 hours, distillate cooling, crystallization, and filtration crystallizes the (root bark of tree peony
Phenol) it is spare；The dregs of a decoction added water to cook with alangium, Radix Glycyrrhizae it is secondary, 2 hours every time, decocting liquid filtration, filtrate merge is concentrated into it is appropriate,
It is dry with above-mentioned powder mixing, it is ground into fine powder, adds right amount of auxiliary materials, is made pellet, it is dry, it is (molten with ethanol in proper amount that Paeonol is added
Solution), mixing is pressed into 1000, sugar coating to get.
Chinese patent (CN102579514) discloses the concocting method of alangium：1) alangium medicinal material is taken, is selected, is cut into
Long section is long to be no more than 15cm；2) succus liquiritiae is prepared：According to 1000 parts of net medicinal materials of alangium, the ratio of 200 portions of Radix Glycyrrhizaes weighs sweet
Grass.The Radix Glycyrrhizae weighed up is decocted 2 times, adds 10 times of amount water, first time to decoct 2h every time, second of decoction 1h is filtered after decocting well, filtered
Liquid is spare；3) according to 1000 parts of net medicinal materials of alangium, the above-mentioned succus liquiritiae prepared is added in milk by the ratio of 500 portions of milk
In, the alangium medicinal material after above-mentioned segment is added, water is added to supply the volume of 14 times of amounts of net medicinal material, decocts 2h, filtration.4) it will cook
Afterwards alangium at 45 DEG C ± 2 DEG C forced air drying to get.
Also some alangiums are taken is extracted with acid extraction and ethyl alcohol, and the present invention is to adopt to be extracted with water, and passes through extraction
Time and sequence different and decoction method difference, alkaloid significantly reduces in alangium, has obtained unexpected effect,
Paeonol takes inclusion compound to be added, the raising of better stability.
It is based on the above reason, inventor improves existing preparation method.Rheumatism stator by alangium, the root of Dahurain angelica,
Four kinds of paniculate swallowwort, Radix Glycyrrhizae bulk pharmaceutical chemicals are made, the content highest of contained alkaloid wherein in alangium, therefore are ensureing curative effect of medication
In the case of, how to reduce the content of alkaloid in alangium is the direction that the present invention mainly studies.The present invention passes through to preparing
The improvement of method, effectively improves Drug safety and stability, reduces the incidence of adverse reaction.
Invention content
Present invention aims at the good rheumatism stators of a kind of safe, few side effects of offer, stability.
The present invention effectively reduces the content of total alkaloid in drug by improving extracting method.Meanwhile passing through beta-cyclodextrin
Paeonol is included, 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：
Alangium 1500g root of Dahurain angelica 50g paniculate swallowwort 150g Radix Glycyrrhizaes 20g
Preparation process is as follows：
(1) it first takes the 50g roots of Dahurain angelica and 15g paniculate swallowworts to be ground into fine powder, sieves for subsequent use；
(2) take remaining 135g paniculate swallowworts to add water, infiltrate 1-3 hours, the sodium chloride of the amount 4-9% of medicinal material is added, with
Steam distillation 3-9 hours, distillate cooling, crystallization filter, and crystallization obtains Paeonol, spare；
(3) after 1500g alangiums being added water to cook 1-2 hours, the paniculate swallowwort dregs of a decoction is added and are added water to cook together with 20g Radix Glycyrrhizaes
1-3 hours, decocting liquid filtration, filtrate was spare, and the dregs of a decoction decoct 1-2 times again, and the time is 1-3 hours, filtering, and filtrate merging is concentrated into suitable
The root of Dahurain angelica and paniculate swallowwort powder mixing is added in amount, dry, is ground into fine powder, adds right amount of auxiliary materials, makes pellet, dry；
(4) Paeonol ethanol solution or paeonol inclusion compound, mixing is then added, is pressed into 1000, sugar coating, i.e.,
.
Wherein, crystal described in step 2 is Paeonol,
Wherein, step 3, alangium and Radix Glycyrrhizae are that successively sequence is extracted, after alangium is first added water to cook 1 hour,
It is added water to cook together 1-3 hours in the addition paniculate swallowwort dregs of a decoction and Radix Glycyrrhizae, decocting liquid filtration, filtrate is spare, and the dregs of a decoction decoct 1-3h again, filter
Liquid merging is concentrated into appropriate, the powder of addition step (1), and mixing is dry, is ground into fine powder, adds right amount of auxiliary materials, makes pellet, dry,
Wherein, Paeonol ethanol solution described in step 4 refers to：Paeonol is dissolved with 95% ethyl alcohol, forms solution.It is preferred that
For Paeonol：Ethyl alcohol=1：3(W/V).
The preparation process of paeonol inclusion compound：Take 100 parts of beta-cyclodextrin that suitable water is added, Paeonol ethyl alcohol is molten being added
10 parts of liquid, stirring and dissolving is ground using colloid mill, is cooled to -1~15 DEG C, and filtering obtains solids, 30~40 DEG C of dryings obtain
To paeonol inclusion compound.
Preferably, preparation method of the invention, includes the following steps：
It takes the 50g roots of Dahurain angelica and 15g paniculate swallowworts to be ground into fine powder, sieves for subsequent use；It takes remaining 135g paniculate swallowworts to add water, is added
The sodium chloride of the amount 4-9% of medicinal material infiltrates 2 hours, steam distillation 6 hours, and distillate cooling, crystallization, filtration crystallizes red
Skin phenol, it is spare；After 1500g alangiums are added water to cook 1 hour, it is small that the addition paniculate swallowwort dregs of a decoction add water to cook 2 together with 20g Radix Glycyrrhizaes
When, decocting liquid filtration, filtrate is spare, and the dregs of a decoction decoct 2h again, filtering, and filtrate, which merges, is concentrated into appropriate, the addition root of Dahurain angelica and paniculate swallowwort powder
Last mixing, it is dry, it is ground into fine powder, adds right amount of auxiliary materials, is made pellet, it is dry, Paeonol ethanol solution or Paeonol inclusion is added
Object, mixing are pressed into 1000, sugar coating to get.
It is further preferred that the preparation method of the present invention,
It takes the 50g roots of Dahurain angelica and 15g paniculate swallowworts to be ground into fine powder, sieves for subsequent use；It takes remaining 135g paniculate swallowworts to add water, is added
The sodium chloride of the amount 4-9% of medicinal material infiltrates 2 hours, steam distillation 6 hours, distillate cooling, crystallization, filtration, and crystallization obtains
Paeonol, while it is spare to obtain aqua aromatica；
After 1500g alangiums are added water to cook 1 hour, it is small that the addition paniculate swallowwort dregs of a decoction add water to cook 2 together with 20g Radix Glycyrrhizaes
When, decocting liquid filtration, filtrate is spare, and the dregs of a decoction decoct 2h again, filtering, and filtrate, which merges, is concentrated into appropriate, the addition root of Dahurain angelica and paniculate swallowwort powder
Last mixing, it is dry, it is ground into fine powder, adds right amount of auxiliary materials, is made pellet, it is dry, paeonol inclusion compound is added, mixing is pressed into 1000
Piece, sugar coating to get,
The preparation of paeonol inclusion compound：Danshinolic acid is dissolved in the ethyl alcohol of 3 times of amounts (V/W), be added 14.3 times (W/W) in
The beta-cyclodextrin of Paeonol is added 45 times (V/W) in the aqua aromatica of beta-cyclodextrin, is ground 4 hours with colloid mill, be cooled to -1
DEG C, filtering obtains solids, low temperature drying obtains inclusion compound.
The rheumatism stator that the present invention is also prepared the above method, carries out total alkaloid content detection, and process is as follows：
Total alkaloid is limited the quantity：This product 20 is taken, sugar-coat is removed, accurately weighed, finely ground, precision draws fine powder appropriate (about 10
Piece weight), it sets in Soxhlet extractor, adds methanol-strong ammonia solution (95：5) mixed solution is appropriate, heating and refluxing extraction to close colourless,
Volatilize methanol, residue is dissolved with 3% sulfuric acid solution 10ml, then uses 3% sulfuric acid solution 10ml, and washing container, washing lotion are incorporated to by several times
In acid solution, add chloroform shaking extraction 2 times, each 20ml, merge chloroform liquid, is carried with 3% sulfuric acid solution 10ml shakings
It takes, discards chloroform liquid, the acid solution before and after merging twice, enriching ammonia solution adjusts pH value and shakes to 9~10, then with chloroform
Extraction 4 times, each 10ml is shaken, chloroform liquid is merged, by being covered with the funnel of anhydrous sodium sulfate 1g, is filtered, filtrate is placed in 105
DEG C dry to be evaporated in water-bath in the evaporating dish of constant weight, residue is dried at 105 DEG C to constant weight, calculate to get.This product every contains
Total alkaloid must not cross 1.2mg.
The present invention reduces the toxic side effect of drug, is carried out to preparation method to reduce the content of total alkaloid in drug
A large amount of screening：
Experiment 1, preparation method screening
1, solvent screening
The 50g roots of Dahurain angelica and paniculate swallowwort 15g are ground into fine powder, sieving.135g paniculate swallowworts add water, infiltrate 2 hours, steam distillation
6 hours, distillate cooling, crystallization filtered, and crystallization (Paeonol) is spare；The dregs of a decoction are carried with 1500g alangiums, 20g Radix Glycyrrhizae solubilizers
Take it is secondary, 2 hours every time, decocting liquid filtration, filtrate merge is concentrated into it is appropriate.
Table 1, the content that gained total alkaloid is extracted using different solvents
| Different solvents | Obtain cream amount | Relative density | Total alkaloid/mg |
| 70% ethyl alcohol | 580 | 1.25 | 1350 |
| 2% aqueous hydrochloric acid solution | 612 | 1.25 | 1089 |
| Water | 560 | 1.25 | 980 |
Experimental result shows, selects ethonal extraction, and in extract in comparison total alkaloid content highest is used
Water extraction effect is best, and the content of total alkaloid controls 1000mg or less.It is therefore preferable that Extraction solvent of the water as the present invention.
2, the extraction of various combination mode
Inventive formulation is made of 4 kinds of bulk pharmaceutical chemicals, one skilled in the art will appreciate that Chinese medicine generally use list is carried or closed and carries
Mode extract.During conjunction carries, different bulk pharmaceutical chemicals are selected to extract together, effect often has differences.In order to more
The content of total alkaloid is controlled well, we screen the extraction of various combination mode：
The 50g roots of Dahurain angelica and paniculate swallowwort 15g are ground into fine powder, sieving.135g paniculate swallowworts add water, infiltrate 2 hours, steam distillation
6 hours, distillate cooling, crystallization filtered, and crystallization (Paeonol) is spare；Extracting mode is shown in Table -2, and decocting liquid filtration, filtrate merges
It is concentrated into appropriate.
Table 2, different modes extraction
| Various combination mode | Decocting time/h | Total alkaloid |
| Paniculate swallowwort and alangium | 2 | 1000 |
| Alangium and Radix Glycyrrhizae | 2 | 930 |
Experimental result shows that alangium closes with Radix Glycyrrhizae and carries, and can effectively reduce the content of total alkaloid.
3, influence of the sodium chloride to extraction is investigated
Scheme 1,135g paniculate swallowworts add water, infiltrate 2 hours, steam distillation 6 hours, distillate cooling, crystallization, filtration,
It is spare to crystallize (Paeonol)；
Scheme 2,135g paniculate swallowworts add water, and the sodium chloride of the amount 4-9% of medicinal material is added, and infiltrate 2 hours, steam distillation 6
Hour, distillate cooling, crystallization filters, and crystallization (Paeonol) is spare；
Table 3, different modes extraction
| Different schemes | Paeonol total amount |
| Scheme 1 | 1.5g |
| Scheme 2 | 2.1g |
Therefore sodium chloride, which is added, contributes to the precipitation of Paeonol.
4, it extracting mode and sequentially screens
It is found in experiment 2, it is preferable that the conjunction of alangium and Radix Glycyrrhizae puies forward effect.Conjunction, which carries, to be divided into first singly to carry respectively, by single extract
Merge extraction；It is also divided into and first singly carries a kind of drug, close carry together remaining drug is added.The present invention also further examines this
It examines.
Scheme 1, alangium first decoct extraction 1 hour, add Radix Glycyrrhizae and the paniculate swallowwort dregs of a decoction decoct extraction 2 hours；
Scheme 2：It is extracted 3 hours after alangium, Radix Glycyrrhizae and the mixing of the paniculate swallowwort dregs of a decoction.
Table 4,
| Various combination mode | Decocting time/h | Decocting time/h | Total alkaloid |
| Alangium | 1 | Radix Glycyrrhizae is added and the paniculate swallowwort dregs of a decoction extract 2 hours | 870 |
| Alangium and Radix Glycyrrhizae and the dregs of a decoction | 2 | 1 | 920 |
Experimental result is shown, using the extracting method of scheme 1, acquired effect is best, can effectively make a price reduction total alkaloid
Content.
By it is above-mentioned it is a series of preferably, obtain the most preferred preparation method of the present invention：
It takes the 50g roots of Dahurain angelica and 15g paniculate swallowworts to be ground into fine powder, sieves for subsequent use；Remaining 135g paniculate swallowworts are taken to add water, infiltration 2
Hour, the sodium chloride of the amount 4-9% of medicinal material is added, steam distillation 6 hours, distillate cooling, crystallization, filtration, filtrate is virtue
Perfume is spare, and crystallization obtains Paeonol, spare；After 1500g alangiums are added water to cook 1 hour, the paniculate swallowwort dregs of a decoction and 20g is added
Radix Glycyrrhizae adds water to cook 2 hours together, and decocting liquid filtration, filtrate is spare, and the dregs of a decoction decoct 1 time, time 2h again, and filtering, filtrate merges
It is concentrated into appropriate, the addition root of Dahurain angelica and paniculate swallowwort powder mixing, it is dry, it is ground into fine powder, adds right amount of auxiliary materials, is made pellet, it is dry, it is added
Paeonol ethanol solution or paeonol inclusion compound, mixing are pressed into 1000, sugar coating to get.
Experiment 2, inclusion technique screening
The present invention includes it in order to improve the stability of Paeonol in rheumatism stator, with beta-cyclodextrin.
At present rheumatism stator particle using be added Paeonol (being dissolved with ethanol in proper amount), tabletting, sugar coating to get.
Since Paeonol is readily volatilized, Qualitive test and assay are unstable, usually directly influence clinical efficacy, because
This is in order to ensure the stability of Paeonol, and the present invention is using beta-cyclodextrin inclusion compound Paeonol.
Its preferred process is as follows：
It takes beta-cyclodextrin to be added to the water dissolving, Paeonol ethanol solution is being added, stirring and dissolving is ground with colloid mill, is dropped
To -1~15 DEG C, filtering obtains 30~40 DEG C of dryings of solids, obtains paeonol inclusion compound temperature.
Table 5, the screening for including process
| Inclusion compound 1 | Inclusion compound 2 | Inclusion compound 3 | Inclusion compound 4 | Inclusion compound 5 | Inclusion compound 6 |
| Beta-cyclodextrin (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 |
| Ethyl alcohol (ml) | 15 | 18 | 18 | 21 | 21 | 24 |
| The time (h) of colloid mill mill | 2 | 2 | 4 | 2 | 4 | 4 |
| Encapsulation rate (%) | 66 | 65 | 66 | 62 | 68 | 56 |
According to the balance of material and rational application, by comparing discovery, inclusion compound 5 is most rationally.
Investigate the stability of inclusion compound and non-inclusion compound
Paeonol method for measuring：
【Assay】It is measured according to high performance liquid chromatography (VI D of annex).
Chromatographic condition is with system suitability using octadecylsilane chemically bonded silica as filler；With acetonitrile-water (38：
26) it is mobile phase；Detection wavelength is 274nm.Number of theoretical plate is calculated by Paeonol peak should be not less than 4000.
The preparation of reference substance solution takes Paeonol reference substance appropriate, accurately weighed, adds methanol that every 1ml is made molten containing 20 μ g
Liquid to get.
The preparation of test solution takes this product 10, removes sugar-coat, accurately weighed, and finely ground, precision draws fine powder about
0.15g is set in 50ml measuring bottles, is added methanol to be ultrasonically treated (power 250W, frequency 33kHz) in right amount 30 minutes, is let cool, add methanol dilute
Release to scale, shake up, filter, take subsequent filtrate to get.
Measuring method is accurate respectively to draw reference substance solution and each 10 μ l of test solution, injects liquid chromatograph, measures, i.e.,
.
Experimental group 1：The 50g roots of Dahurain angelica and paniculate swallowwort 15g are ground into fine powder, sieving.135g paniculate swallowworts add water, infiltrate 2 hours, water
Steam distillation 6 hours, distillate cooling, crystallization, filtration, crystallization (Paeonol) are spare；Alangium 1500g is added water to cook 1 hour,
The dregs of a decoction and 20g Radix Glycyrrhizaes add water to cook 2 hours, and decocting liquid filtration, the dregs of a decoction decoct once again, and filtrate, which merges, to be concentrated into right amount, and upper
Powder mixing is stated, it is dry, it is ground into fine powder, adds right amount of auxiliary materials, is made pellet, it is dry, Paeonol (being dissolved with ethanol in proper amount) is added, mixes
It is even, be pressed into 1000, sugar coating to get.
Experimental group 2：The 50g roots of Dahurain angelica and paniculate swallowwort 15g are ground into fine powder, sieving.135g paniculate swallowworts add water, and the amount of medicinal material is added
The sodium chloride of 4-9% infiltrates 2 hours, steam distillation 6 hours, distillate cooling, crystallization, filtration, and crystallization (Paeonol) is standby
With；Alangium 1500g is added water to cook 1 hour, is added water to cook 2 hours with 20g Radix Glycyrrhizaes the paniculate swallowwort dregs of a decoction are added, decocting liquid filtration,
The dregs of a decoction decoct once again, and filtrate, which merges, to be concentrated into right amount, dry with above-mentioned powder mixing, is ground into fine powder, is added right amount of auxiliary materials, makes
Particle, it is dry, be added inclusion compound 5, mixing is pressed into 1000, sugar coating to get.
6 rheumatism stator 6 months accelerated stabilities of Paeonol of table are investigated
Experimental result is shown：After inclusion compound is made in Paeonol, stability is increased dramatically, than directly using the root bark of tree peony
The tabletting effect of phenol is more preferable.
Experiment 3, total alkaloid content compare
Experimental group：The rheumatism stator for selecting the embodiment of the present invention 1 to prepare.
Control group：Commercially available rheumatism stator.
Detection method：This product 20 is taken, sugar-coat is removed, accurately weighed, finely ground, it is (about 10 appropriate that precision draws fine powder
Weight), it sets in Soxhlet extractor, adds methanol-strong ammonia solution (95：5) mixed solution is appropriate, and heating and refluxing extraction is waved to close colourless
Dry methanol, residue are dissolved with 3% sulfuric acid solution 10ml, then use 3% sulfuric acid solution 10ml, and washing container, washing lotion are incorporated to acid by several times
In liquid, add chloroform shaking extraction 2 times, each 20ml, merge chloroform liquid, is extracted with 3% sulfuric acid solution 10ml shakings,
Chloroform liquid is discarded, the acid solution before and after merging twice, enriching ammonia solution adjusts pH value and shaken to 9~10, then with chloroform
Extraction 4 times, each 10ml merges chloroform liquid, by being covered with the funnel of anhydrous sodium sulfate 1g, filters, filtrate is placed in 105 DEG C
Dry to be evaporated in water-bath in the evaporating dish of constant weight, residue is dried at 105 DEG C to constant weight, calculate to get.
Table 7, total alkaloid content compare
| Total alkaloid content in every rheumatism stator | |
| Experimental group | 0.6mg |
| Control group | 1.0mg |
Experimental result shows that rheumatism stator of the invention is relative to commercially available rheumatism stator, and alkaloid is less, medicine
Object safety higher.
The present invention effectively improves the safety and stability of drug by the adjustment to preparation method, reduces toxic side effect.
The preparation process of the present invention is simple, requires operating environment low, at low cost, suitable large-scale production.
Specific implementation mode
By following embodiment, the present invention is further illustrated, but without limitation.
Embodiment 1
The 50g roots of Dahurain angelica and paniculate swallowwort 15g are ground into fine powder, sieve for subsequent use；It takes 135g paniculate swallowworts to add water, the amount of medicinal material is added
The sodium chloride of 4-9% infiltrates 2 hours, steam distillation 6 hours, distillate cooling, crystallization, filtration, and crystallization obtains Paeonol,
It is spare to obtain aqua aromatica simultaneously；
Paeonol is taken to be added in ethyl alcohol (Paeonol：Proportion of ethanol is 1g:Paeonol ethanol solution 3ml) is obtained, molten
Beta-cyclodextrin (the Paeonol of 14.3 times of Paeonols is added in liquid：Beta-cyclodextrin ratio is 1g:14.3g), 45 times of β-are added
Aqua aromatica (the aqua aromatica of cyclodextrin：Beta-cyclodextrin ratio is 45g:1g), it is ground 4 hours with colloid mill, is cooled to -1 DEG C, filtered,
Solids is obtained, low temperature drying obtains paeonol inclusion compound；
Alangium 1500g is added water to cook 1 hour, and the paniculate swallowwort dregs of a decoction add water to cook 2 hours with 20g Radix Glycyrrhizaes, decocting liquid filtration, medicine
Slag decocts once again, decocts 2 hours, and filtrate, which merges, to be concentrated into right amount, dry with above-mentioned powder mixing, is ground into fine powder, is added auxiliary material
In right amount, make pellet, it is dry, be added paeonol inclusion compound, mixing is pressed into 1000, sugar coating to get.
Embodiment 2
The 50g roots of Dahurain angelica and 15g paniculate swallowworts are ground into fine powder, and sieving, 135g paniculate swallowworts add water, are added the amount 4-9%'s of medicinal material
Sodium chloride, infiltrate 2 hours, steam distillation 6 hours, distillate cooling, crystallization, filtration, crystallize (Paeonol), the dregs of a decoction and
1500g alangiums, 20g Radix Glycyrrhizaes add water to cook it is secondary, 2 hours every time, decocting liquid filtration, filtrate merge be concentrated into it is appropriate, and it is above-mentioned
Powder mixing, it is dry, it is ground into fine powder, adds right amount of auxiliary materials, is made pellet, it is dry, Paeonol (being dissolved with ethanol in proper amount) is added, mixes
It is even, be pressed into 1000, sugar coating to get.
Embodiment 3
The 50g roots of Dahurain angelica and paniculate swallowwort 15g are ground into fine powder, sieve for subsequent use；It takes 135g paniculate swallowworts to add water, the amount of medicinal material is added
The sodium chloride of 4-9% infiltrates 1 hour, steam distillation 3 hours, distillate cooling, crystallization, and filtration is crystallized the (root bark of tree peony
Phenol), while it is spare to obtain aqua aromatica；Paeonol, which is added in the ethyl alcohol of 3 times of amounts, dissolves (Paeonol：Proportion of ethanol is 1g:3ml),
In the beta-cyclodextrin (Paeonol that 14.3 times of Paeonols are added：Beta-cyclodextrin ratio is 1g:14.3g), 45 times of β-rings are added
The aqua aromatica of dextrin, (aqua aromatica：Beta-cyclodextrin ratio is 45g:It 1g) is ground 4 hours with colloid mill, is cooled to -1 DEG C, filtering obtains
To solids, low temperature drying obtains inclusion compound.
Alangium 1500g is added water to cook 1 hour, and the paniculate swallowwort dregs of a decoction add water to cook 1 hour with 20g Radix Glycyrrhizaes, decocting liquid filtration,
The dregs of a decoction decoct once again, decoct 2 hours, and filtrate, which merges, to be concentrated into right amount, dry with above-mentioned powder mixing, is ground into fine powder, is added auxiliary
Material is appropriate, makes pellet, dry, and paeonol inclusion compound (being converted to Paeonol 1.8g) is added, and mixing is pressed into 1000, packet sugar
Clothing to get.
Embodiment 4
The 50g roots of Dahurain angelica and paniculate swallowwort 15g are ground into fine powder, sieve for subsequent use；It takes 135g paniculate swallowworts to add water, the amount of medicinal material is added
The sodium chloride of 4-9% infiltrates 3 hours, steam distillation 9 hours, distillate cooling, crystallization, and filtration is crystallized the (root bark of tree peony
Phenol), while it is spare to obtain aqua aromatica；Paeonol, which is added in the ethyl alcohol of 3 times of amounts, dissolves (Paeonol：Proportion of ethanol is 1g:3ml),
In the beta-cyclodextrin (Paeonol that 14.3 times of Paeonols are added：Beta-cyclodextrin ratio is 1g:14.3g), 45 times of β-rings are added
Aqua aromatica (the aqua aromatica of dextrin：Beta-cyclodextrin ratio is 45g:1g), it is ground 4 hours with colloid mill, is cooled to -1 DEG C, filtering obtains
To solids, low temperature drying obtains inclusion compound.
Alangium 1500g is added water to cook 1 hour, and the paniculate swallowwort dregs of a decoction add water to cook 2 hours with 20g Radix Glycyrrhizaes, decocting liquid filtration,
The dregs of a decoction decoct once again, decoct 2 hours, and filtrate, which merges, to be concentrated into right amount, dry with above-mentioned powder mixing, is ground into fine powder, is added auxiliary
Material is appropriate, makes pellet, dry, is added paeonol inclusion compound, mixing, is pressed into 1000, sugar coating to get.
Embodiment 5
The assay of Paeonol is as follows：Chromatographic condition is with octadecylsilane chemically bonded silica with system suitability
Filler；With acetonitrile-water (38：26) it is mobile phase；Detection wavelength is 274nm.Number of theoretical plate should not be low by the calculating of Paeonol peak
In 4000.
The preparation of reference substance solution takes Paeonol reference substance appropriate, accurately weighed, adds methanol that every 1ml is made molten containing 20 μ g
Liquid to get.
The preparation of test solution takes the crystal 15mg of step 2 of the present invention, accurately weighed, adds methanol that every 1ml is made and contains
The solution of 20 μ g to get.
Measuring method is accurate respectively to draw reference substance solution and each 10 μ l of test solution, injects liquid chromatograph, measures, i.e.,
.
For crystal in terms of Paeonol (C9H10O3), content must not be less than 95%.
Claims (2)
1. a kind of preparation method of rheumatism stator, which is characterized in that steps are as follows：
It takes the 50g roots of Dahurain angelica and 15g paniculate swallowworts to be ground into fine powder, sieves for subsequent use；It takes remaining 135g paniculate swallowworts to add water, medicinal material is added
Amount 4-9% sodium chloride, infiltrate 2 hours, steam distillation 6 hours, distillate cooling, crystallization, filtration, crystallize to obtain the root bark of tree peony
Phenol, it is spare；After 1500g alangiums are added water to cook 1 hour, it is small that the addition paniculate swallowwort dregs of a decoction add water to cook 2 together with 20g Radix Glycyrrhizaes
When, decocting liquid filtration, filtrate is spare, and the dregs of a decoction decoct 2h again, filtering, and filtrate, which merges, is concentrated into appropriate, the addition root of Dahurain angelica and paniculate swallowwort powder
Last mixing, it is dry, it is ground into fine powder, adds right amount of auxiliary materials, is made pellet, it is dry, paeonol inclusion compound is added, mixing is pressed into 1000
Piece, sugar coating to get.
2. preparation method according to claim 1, which is characterized in that steps are as follows：
It takes the 50g roots of Dahurain angelica and 15g paniculate swallowworts to be ground into fine powder, sieves for subsequent use；It takes remaining 135g paniculate swallowworts to add water, medicinal material is added
Amount 4-9% sodium chloride, infiltrate 2 hours, steam distillation 6 hours, distillate cooling, crystallization, filtration, crystallization obtain the root bark of tree peony
Phenol, while it is spare to obtain aqua aromatica；
After 1500g alangiums are added water to cook 1 hour, the paniculate swallowwort dregs of a decoction are added and are added water to cook together with 20g Radix Glycyrrhizaes 2 hours, decoct
Liquid filters, and filtrate is spare, and the dregs of a decoction decoct 2h again, filtering, and filtrate, which merges, to be concentrated into right amount, and the root of Dahurain angelica is added and paniculate swallowwort powder is mixed
It is even, it is dry, it is ground into fine powder, adds right amount of auxiliary materials, is made pellet, it is dry, paeonol inclusion compound is added, mixing is pressed into 1000, packet
Sugar-coat to get,
Wherein, the preparation of paeonol inclusion compound：Danshinolic acid is dissolved in the ethyl alcohol of 3 times of amounts (V/W), is added 14.3 times (W/W)
In the beta-cyclodextrin of Paeonol, 45 times (V/W) are added in the aqua aromatica of beta-cyclodextrin, is ground 4 hours with colloid mill, is cooled to -1
DEG C, filtering obtains solids, low temperature drying obtains inclusion compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410834244.XA CN104490990B (en) | 2014-12-29 | 2014-12-29 | A kind of preparation method of rheumatism stator |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410834244.XA CN104490990B (en) | 2014-12-29 | 2014-12-29 | A kind of preparation method of rheumatism stator |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104490990A CN104490990A (en) | 2015-04-08 |
| CN104490990B true CN104490990B (en) | 2018-07-13 |
Family
ID=52932504
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410834244.XA Active CN104490990B (en) | 2014-12-29 | 2014-12-29 | A kind of preparation method of rheumatism stator |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104490990B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102370691A (en) * | 2010-08-26 | 2012-03-14 | 江西济民可信集团有限公司 | Ibufenac traditional Chinese preparation detection method |
-
2014
- 2014-12-29 CN CN201410834244.XA patent/CN104490990B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102370691A (en) * | 2010-08-26 | 2012-03-14 | 江西济民可信集团有限公司 | Ibufenac traditional Chinese preparation detection method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104490990A (en) | 2015-04-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1899361B (en) | Zhenqi medicinal composition and its preparation | |
| CN101491546B (en) | Traditional Chinese medicine formulation granules containing volatile oil and preparation method thereof | |
| CN101297864A (en) | Preparation of Xia sang ju formulation | |
| CN102743401B (en) | Application of panaxadiol saponins fraction in preparing medicine for preventing epilepsia | |
| CN102068510A (en) | Pharmaceutical composition for treating liver diseases and preparation method thereof | |
| CN100584348C (en) | Anti-hepatitis medical combination | |
| CN102302615B (en) | Effective site group of daphne giraldii nitsche leaf, preparation method, medicinal composition and application thereof | |
| CN100512796C (en) | Medicinal composition containing scutellaria glucoside and bupleurum and its preparation method | |
| CN101406542B (en) | Chinese medicine oral preparation for relieving cough, relieving asthma and dispelling phlegm | |
| CN104490990B (en) | A kind of preparation method of rheumatism stator | |
| CN110227091A (en) | The extraction of paniculate swallowwort medicinal ingredient and its granule and preparation method | |
| CN101712618B (en) | Two crystal form materials of salvianolic acid A, preparation method as well as medicine compound and application thereof | |
| CN1686424B (en) | Medicinal composition containing scutellaria and bupleurum and its preparation method | |
| CN106535912B (en) | Control pharmaceutical composition and its application of human body blood fat and body weight | |
| CN101129974A (en) | Traditional Chinese medicine composition for treating hepatopathy and method of preparing the same | |
| CN1985873B (en) | Medicine composition of glycyrrhizic acid or its salt, ginseng and astragalus root | |
| CN100531721C (en) | Dysmenorrhea treating solid medicine preparation and its preparation process | |
| CN104857087A (en) | Pharmaceutic preparation with blood glucose reducing effect, and preparation method and application of pharmaceutic preparation | |
| CN101347567B (en) | Effective component of airpotato yam as well as preparation method and use thereof | |
| CN101428064B (en) | Effective component of schisandra chinensis, preparation method and use thereof | |
| CN101912453B (en) | Medicinal composition with anti-inflammatory and analgesic effects and preparation method and application thereof | |
| CN103446307B (en) | A kind of Chinese medicine composition for the treatment of diabetic foot | |
| CN106361811A (en) | Tongmai pharmaceutical composition and preparation method thereof | |
| CN106309522B (en) | Clear Yiganning capsule of bavin a kind of reed mentioned in ancient books and preparation method thereof | |
| CN101219192B (en) | Chinese medicine composition, preparation for treating mammary gland hyperplasia and method for preparing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 336000 Yuanzhou pharmaceutical industry park, Jiangxi, Yichun Co-patentee after: Jiangxi Jinshuibao Pharmaceutical Co.,Ltd. Patentee after: JIANGXI JIMINKEXIN PHARMACEUTICAL Co.,Ltd. Address before: 336000 Yuanzhou pharmaceutical industry park, Jiangxi, Yichun Co-patentee before: JIANGXI JIMINKEXIN JINSHUIBAO PHARMACEUTICAL Co.,Ltd. Patentee before: JIANGXI JIMINKEXIN PHARMACEUTICAL Co.,Ltd. |
|
| CP01 | Change in the name or title of a patent holder | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A preparation method of rheumatoid tablets Effective date of registration: 20211224 Granted publication date: 20180713 Pledgee: Bank of China Limited Nanchang Qingyunpu sub branch Pledgor: Jiangxi Jinshuibao Pharmaceutical Co.,Ltd. Registration number: Y2021980016165 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20220902 Granted publication date: 20180713 Pledgee: Bank of China Limited Nanchang Qingyunpu sub branch Pledgor: Jiangxi Jinshuibao Pharmaceutical Co.,Ltd. Registration number: Y2021980016165 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A kind of preparation method of rheumatism tablet Effective date of registration: 20220905 Granted publication date: 20180713 Pledgee: Bank of China Limited Nanchang Qingyunpu sub branch Pledgor: Jiangxi Jinshuibao Pharmaceutical Co.,Ltd. Registration number: Y2022980014590 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230830 Granted publication date: 20180713 Pledgee: Bank of China Limited Nanchang Qingyunpu sub branch Pledgor: Jiangxi Jinshuibao Pharmaceutical Co.,Ltd. Registration number: Y2022980014590 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A preparation method for Fengshiding tablets Effective date of registration: 20230831 Granted publication date: 20180713 Pledgee: Bank of China Limited Nanchang Qingyunpu sub branch Pledgor: Jiangxi Jinshuibao Pharmaceutical Co.,Ltd. Registration number: Y2023980054963 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |