CN116236529B - Cicada itching-relieving composition capsule for improving content of marking components and preparation method thereof - Google Patents
Cicada itching-relieving composition capsule for improving content of marking components and preparation method thereof Download PDFInfo
- Publication number
- CN116236529B CN116236529B CN202310448644.6A CN202310448644A CN116236529B CN 116236529 B CN116236529 B CN 116236529B CN 202310448644 A CN202310448644 A CN 202310448644A CN 116236529 B CN116236529 B CN 116236529B
- Authority
- CN
- China
- Prior art keywords
- powder
- extraction
- parts
- cicada
- medicinal
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 78
- 239000002775 capsule Substances 0.000 title claims abstract description 62
- 241000931705 Cicada Species 0.000 title claims abstract description 48
- 208000003251 Pruritus Diseases 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 238000000605 extraction Methods 0.000 claims abstract description 76
- 238000000194 supercritical-fluid extraction Methods 0.000 claims abstract description 56
- 239000003814 drug Substances 0.000 claims abstract description 55
- 238000000034 method Methods 0.000 claims abstract description 40
- 238000005325 percolation Methods 0.000 claims abstract description 27
- 230000007803 itching Effects 0.000 claims abstract description 14
- 239000000843 powder Substances 0.000 claims description 132
- 239000000463 material Substances 0.000 claims description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 51
- 238000004108 freeze drying Methods 0.000 claims description 43
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 40
- 239000000284 extract Substances 0.000 claims description 29
- 238000001035 drying Methods 0.000 claims description 21
- 238000010438 heat treatment Methods 0.000 claims description 21
- 239000000741 silica gel Substances 0.000 claims description 17
- 238000002156 mixing Methods 0.000 claims description 16
- 230000008569 process Effects 0.000 claims description 14
- 239000002994 raw material Substances 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- 235000013399 edible fruits Nutrition 0.000 claims description 12
- 238000011049 filling Methods 0.000 claims description 12
- 235000001405 Artemisia annua Nutrition 0.000 claims description 11
- 240000000011 Artemisia annua Species 0.000 claims description 11
- 238000007873 sieving Methods 0.000 claims description 11
- 229910002027 silica gel Inorganic materials 0.000 claims description 11
- 241000205585 Aquilegia canadensis Species 0.000 claims description 10
- 244000111489 Gardenia augusta Species 0.000 claims description 9
- 241001071795 Gentiana Species 0.000 claims description 9
- 241000972673 Phellodendron amurense Species 0.000 claims description 8
- 239000000377 silicon dioxide Substances 0.000 claims description 8
- 244000303040 Glycyrrhiza glabra Species 0.000 claims description 7
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims description 7
- 240000002505 Pogostemon cablin Species 0.000 claims description 7
- 235000011751 Pogostemon cablin Nutrition 0.000 claims description 7
- 241000405414 Rehmannia Species 0.000 claims description 7
- 238000007710 freezing Methods 0.000 claims description 7
- 230000008014 freezing Effects 0.000 claims description 7
- 241000213006 Angelica dahurica Species 0.000 claims description 6
- 241000212948 Cnidium Species 0.000 claims description 6
- 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 claims description 5
- 235000011477 liquorice Nutrition 0.000 claims description 5
- 238000010298 pulverizing process Methods 0.000 claims description 5
- 238000007789 sealing Methods 0.000 claims description 5
- MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 claims description 4
- 240000000774 Cunila origanoides Species 0.000 claims description 4
- 235000018274 Cunila origanoides Nutrition 0.000 claims description 4
- 235000014866 Dictamnus albus Nutrition 0.000 claims description 4
- 241000219784 Sophora Species 0.000 claims description 4
- 239000002674 ointment Substances 0.000 claims description 4
- 239000002245 particle Substances 0.000 claims description 3
- 238000009736 wetting Methods 0.000 claims description 3
- 241000405911 Rehmannia glutinosa Species 0.000 claims 2
- 241000050051 Chelone glabra Species 0.000 claims 1
- 239000013058 crude material Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 14
- 238000006243 chemical reaction Methods 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 10
- 230000000052 comparative effect Effects 0.000 description 67
- 239000000243 solution Substances 0.000 description 46
- VKJGBAJNNALVAV-UHFFFAOYSA-M Berberine chloride (TN) Chemical compound [Cl-].C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 VKJGBAJNNALVAV-UHFFFAOYSA-M 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000047 product Substances 0.000 description 30
- IPQKDIRUZHOIOM-UHFFFAOYSA-N Oroxin A Natural products OC1C(O)C(O)C(CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IPQKDIRUZHOIOM-UHFFFAOYSA-N 0.000 description 28
- IKIIZLYTISPENI-ZFORQUDYSA-N baicalin Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IKIIZLYTISPENI-ZFORQUDYSA-N 0.000 description 28
- 229960003321 baicalin Drugs 0.000 description 28
- AQHDANHUMGXSJZ-UHFFFAOYSA-N baicalin Natural products OC1C(O)C(C(O)CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 AQHDANHUMGXSJZ-UHFFFAOYSA-N 0.000 description 28
- 239000008187 granular material Substances 0.000 description 17
- 229940079593 drug Drugs 0.000 description 16
- 238000012360 testing method Methods 0.000 description 13
- 238000005303 weighing Methods 0.000 description 13
- 238000012792 lyophilization process Methods 0.000 description 11
- 230000001139 anti-pruritic effect Effects 0.000 description 10
- 239000003908 antipruritic agent Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000003550 marker Substances 0.000 description 9
- 229910021487 silica fume Inorganic materials 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000000523 sample Substances 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 7
- 239000012488 sample solution Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- 230000009286 beneficial effect Effects 0.000 description 6
- 238000005265 energy consumption Methods 0.000 description 6
- 239000000945 filler Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 238000011068 loading method Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000013558 reference substance Substances 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 241001529821 Agastache Species 0.000 description 3
- 241000207929 Scutellaria Species 0.000 description 3
- 240000004534 Scutellaria baicalensis Species 0.000 description 3
- 235000017089 Scutellaria baicalensis Nutrition 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000000857 drug effect Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000002893 slag Substances 0.000 description 3
- 239000012085 test solution Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 241000576429 Forsythia suspensa Species 0.000 description 2
- XJMPAUZQVRGFRE-SCHFUKFYSA-N Gardenoside Natural products O=C(OC)C=1[C@H]2[C@H]([C@H](O[C@H]3[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O3)OC=1)[C@@](O)(CO)C=C2 XJMPAUZQVRGFRE-SCHFUKFYSA-N 0.000 description 2
- IBFYXTRXDNAPMM-BVTMAQQCSA-N Geniposide Chemical compound O([C@@H]1OC=C([C@@H]2[C@H]1C(=CC2)CO)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O IBFYXTRXDNAPMM-BVTMAQQCSA-N 0.000 description 2
- IBFYXTRXDNAPMM-FZEIBHLUSA-N Geniposide Natural products COC(=O)C1=CO[C@@H](O[C@H]2O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]2O)[C@H]2[C@@H]1CC=C2CO IBFYXTRXDNAPMM-FZEIBHLUSA-N 0.000 description 2
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 2
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- MHLMRBVCMNDOCW-UHFFFAOYSA-N acetic acid;butan-1-ol;hydrate Chemical compound O.CC(O)=O.CCCCO MHLMRBVCMNDOCW-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- VGLLGNISLBPZNL-RBUKDIBWSA-N arborescoside Natural products O=C(OC)C=1[C@@H]2C([C@H](O[C@H]3[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O3)OC=1)=C(CO)CC2 VGLLGNISLBPZNL-RBUKDIBWSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 229940010454 licorice Drugs 0.000 description 2
- XJMPAUZQVRGFRE-AYDWLWLASA-N methyl (1s,4as,7s,7as)-7-hydroxy-7-(hydroxymethyl)-1-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4a,7a-dihydro-1h-cyclopenta[c]pyran-4-carboxylate Chemical compound O([C@@H]1OC=C([C@@H]2[C@H]1[C@](C=C2)(O)CO)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O XJMPAUZQVRGFRE-AYDWLWLASA-N 0.000 description 2
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 239000012088 reference solution Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000003892 spreading Methods 0.000 description 2
- 230000007480 spreading Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 230000001502 supplementing effect Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 238000009210 therapy by ultrasound Methods 0.000 description 2
- 239000000341 volatile oil Substances 0.000 description 2
- DGLDSNPMIYUWGN-OOJQBDKLSA-N (13as)-3,10-dimethoxy-7-methyl-6,8,13,13a-tetrahydro-5h-isoquinolino[2,1-b]isoquinolin-7-ium-2,11-diol;chloride Chemical compound [Cl-].C1CC2=CC(OC)=C(O)C=C2[C@H]2[N+]1(C)CC(C=C(C(=C1)O)OC)=C1C2 DGLDSNPMIYUWGN-OOJQBDKLSA-N 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 241000628997 Flos Species 0.000 description 1
- 235000018958 Gardenia augusta Nutrition 0.000 description 1
- 241001162994 Rugosus Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 241000246044 Sophora flavescens Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- WXYIONYJZVWSIJ-UHFFFAOYSA-N acetonitrile;methanol;hydrate Chemical compound O.OC.CC#N WXYIONYJZVWSIJ-UHFFFAOYSA-N 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 description 1
- 229940093265 berberine Drugs 0.000 description 1
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 description 1
- ONBIUAZBGHXJDM-UHFFFAOYSA-J bismuth;potassium;tetraiodide Chemical compound [K+].[I-].[I-].[I-].[I-].[Bi+3] ONBIUAZBGHXJDM-UHFFFAOYSA-J 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
- LYBCHMBMGSZNOA-UHFFFAOYSA-N dichloromethane;formic acid;methanol Chemical compound OC.OC=O.ClCCl LYBCHMBMGSZNOA-UHFFFAOYSA-N 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 238000000622 liquid--liquid extraction Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- JWHHANVGNNWIRI-UHFFFAOYSA-N methanol phosphoric acid hydrate Chemical compound O.OC.OP(O)(O)=O JWHHANVGNNWIRI-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003815 supercritical carbon dioxide extraction Methods 0.000 description 1
- -1 taken out Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 238000005550 wet granulation 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)
- A61K36/35—Caprifoliaceae (Honeysuckle family)
- A61K36/355—Lonicera (honeysuckle)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/63—Arthropods
- A61K35/64—Insects, e.g. bees, wasps or fleas
-
- 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)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/234—Cnidium (snowparsley)
-
- 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)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/282—Artemisia, e.g. wormwood or sagebrush
-
- 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
- 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
- A61K36/489—Sophora, e.g. necklacepod or mamani
-
- 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)
- A61K36/51—Gentianaceae (Gentian family)
- A61K36/515—Gentiana
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/532—Agastache, e.g. giant hyssop
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/539—Scutellaria (skullcap)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
- A61K36/634—Forsythia
-
- 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)
- A61K36/74—Rubiaceae (Madder family)
- A61K36/744—Gardenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/75—Rutaceae (Rue family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/75—Rutaceae (Rue family)
- A61K36/756—Phellodendron, e.g. corktree
-
- 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)
- A61K36/80—Scrophulariaceae (Figwort family)
- A61K36/804—Rehmannia
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/485—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- 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
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- 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
- A61K2236/37—Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
-
- 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
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Botany (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Insects & Arthropods (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Animal Husbandry (AREA)
- Zoology (AREA)
- Inorganic Chemistry (AREA)
- Neurosurgery (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention relates to the technical field of traditional Chinese medicine composition production processes, and discloses a cicada itching relieving composition capsule for improving the content of a marked component and a preparation method thereof. By adopting supercritical extraction and percolation extraction, the preparation stage does not need to consume large-scale energy, so that the production cost is reduced and the production efficiency is greatly improved; the method also solves the technical problem that the content of the marked components in the medicine is reduced due to compatibility reaction in the existing preparation method, and can effectively improve the content of the marked components in the medicine, thereby improving the quality and curative effect of the medicine.
Description
Technical Field
The invention relates to the technical field of traditional Chinese medicine composition production processes, in particular to a cicada itching-relieving composition capsule for improving the content of a marked component and a preparation method thereof.
Background
The cicada itching relieving capsule is a pure Chinese medicine capsule preparation and contains the components of honeysuckle, cicada slough, agastache rugosus and the like. The main functions of the medicine are clearing heat and detoxicating, eliminating dampness and relieving itching. Can be used for treating dermatoses such as urticaria, dermatitis, and eczema.
At present, high-temperature procedures such as decocting, extracting, concentrating, wet granulating, boiling drying and the like are often adopted to prepare the product, so that serious compatibility reaction can occur in the preparation process of berberine hydrochloride in phellodendron bark, baicalin in baicalensis, and the like, so that the transfer rate of berberine hydrochloride and baicalin serving as marker components in the product to a finished product is very low, and even the content of berberine hydrochloride and baicalin does not meet the quality standard; in addition, the existing extraction process steps are divided into two units: the extraction unit comprises decoction, extraction and concentration; the preparation units comprise wet granulation and boiling drying, and the energy consumption in each unit is very high, so that the production cost is quite high, and the market competition of products is not facilitated.
Therefore, development of a cicada itching-relieving composition product capable of improving the content of a marking component in the product and reducing the energy consumption and a preparation method thereof are needed, so that the defects of the existing cicada itching-relieving composition product and the preparation process can be effectively overcome, and the cicada itching-relieving composition product has important significance for improving the quality of the product and the market competitiveness of the product.
Disclosure of Invention
The invention aims to provide a cicada itching-relieving composition capsule for improving the content of a marking component and a preparation method thereof, so as to solve the technical problem that the content is reduced and the drug effect is reduced due to compatibility reaction of the marking component when the cicada itching-relieving capsule is prepared in the prior art.
In order to achieve the above purpose, the invention adopts the following technical scheme: the cicada antipruritic composition capsule for improving the content of the marking components comprises the following medicinal materials of 350-450 parts of honeysuckle, 350-450 parts of cape jasmine, 350-450 parts of baical skullcap root, 350-450 parts of lightyellow sophora root, 250-350 parts of amur corktree bark, 350-450 parts of dahurian angelica root, 250-350 parts of gentian, 350-450 parts of dittany bark, 350-450 parts of common cnidium fruit, 350-450 parts of belvedere fruit, 350-450 parts of weeping forsythiae capsule, 150-250 parts of cicada slough, 350-450 parts of patchouli, 550-650 parts of rehmannia root, 550-650 parts of sweet wormwood and 250-350 parts of liquorice; the preparation method comprises the following steps: sequentially performing supercritical extraction and diacolation extraction on the raw materials to obtain supercritical extraction powder and diacolation extraction powder, combining the supercritical extraction powder and diacolation extraction powder, uniformly mixing with superfine silica powder, and filling into capsules to obtain the cicada itching-relieving composition capsules.
The principle and beneficial effect of this scheme lie in:
in the preparation process of the cicada antipruritic composition capsule, the medicinal materials are firstly mixed, crushed and sieved to prepare coarse medicinal material powder, and then the medicinal components in the coarse medicinal material powder are subjected to supercritical extraction to obtain supercritical extraction medicinal powder and primary extraction residues; then, percolating and extracting the traditional Chinese medicine components of the primary extracted dregs to obtain percolating and extracting medicinal powder, and combining the supercritical extraction medicinal powder and the percolating and extracting medicinal powder to obtain all the medicinal active components of the product; finally, the superfine silica powder is taken as a medicinal auxiliary material to be mixed with the supercritical extraction medicinal powder and the diacolation extraction medicinal powder to form a total mixture, and the total mixture is filled into capsules to form the cicada itching-relieving composition capsules.
In the scheme, the supercritical extraction and the percolation extraction are low-temperature extraction processes, so that the content of berberine hydrochloride and baicalin serving as the marker components can be effectively prevented from being reduced due to compatibility reaction in the high-temperature extraction process, the content of the two marker components in the medicine can be effectively improved, and the quality and the curative effect of the medicine can be further improved. The applicant finds that when the phellodendron bark and the baicalin are mixed and extracted by adopting high-temperature processes such as a steam distillation method, a water decoction method and the like through a large number of researches, the marked components berberine hydrochloride and baicalin can generate serious compatibility reaction, so that the content of the baicalin and the berberine hydrochloride in the medicine is reduced. In order to avoid the compatibility reaction between the two, the applicant then conceived another direction of improvement: the two are separated by adopting a step extraction and layering granulation technology so as to avoid the compatibility reaction of the two to reduce the content; if the mixed extract of cortex phellodendri and part of medicinal materials is used as a core, the mixed extract of radix scutellariae and part of medicinal materials is used as an outer layer, and a sealing layer for wrapping the core is arranged between the two layers, so that the aim of separating berberine hydrochloride from radix scutellariae and avoiding compatibility reaction of berberine hydrochloride and radix scutellariae is fulfilled. However, in this way of layered granulation, although the compatibility reaction between the two is prevented in space, the production energy consumption is increased, and the dosage of auxiliary materials for medicines and medicines is additionally increased, so that the risk of stress reaction during the administration of medicines and medicines for patients is increased. Finally, the applicant thinks that starting from the extraction process, the extraction temperature is reduced to improve the phenomenon that the marked components react in a compatibility way, and the content of the two marked components in the medicine is improved.
The applicant detects that the content of berberine hydrochloride in the capsule prepared by the scheme is up to 3.7 mg/granule, the content of baicalin is up to 21.6 mg/granule, and the content of berberine hydrochloride is obviously higher than the minimum standard of the content of the marked components of the cicada antipruritic capsule in the Chinese pharmacopoeia of 2020 edition (berberine hydrochloride is not lower than 0.4 mg/granule and baicalin is not lower than 4.6 mg/granule), thereby effectively improving the quality and the drug effect of the medicine. In addition, the supercritical extraction and the percolation extraction are adopted in the scheme, large-scale energy consumption is not required in the preparation stage, and the preparation method is environment-friendly, the production efficiency is greatly improved, and the production cost is greatly reduced. In addition, the medicine of the scheme only comprises the superfine silica gel powder and the medicinal material extract, and the dosage of auxiliary materials for the traditional Chinese medicine is reduced, so that the risk of stress reaction when a patient takes the medicine is obviously reduced, and the safety of the medicine is improved.
The technical scheme also provides a preparation method of the cicada itching-relieving composition capsule for improving the content of the marking components, which comprises the following steps:
s1, preparing supercritical extraction medicinal powder: mixing the raw materials according to the parts by weight, namely honeysuckle, gardenia, baical skullcap root, lightyellow sophora root, amur corktree bark, dahurian angelica root, gentian, cortex dictamni, common cnidium fruit, belvedere fruit, weeping forsythiae capsule, cicada slough, patchouli, rehmannia root, sweet wormwood herb and liquoric root, crushing and sieving to obtain crude powder of 16-20 meshes, carrying out supercritical extraction on the crude powder of the medicinal materials for 3 times to obtain primary extract powder and primary extract dregs, and crushing and sieving the primary extract powder to obtain supercritical extract powder;
s2, preparing diacolated extract powder: percolating and extracting the primary extraction residues obtained in the step S1 to obtain percolate; concentrating, lyophilizing and pulverizing the percolate to obtain percolate extract powder;
s3, preparing a total mixture: mixing the supercritical extraction powder obtained in the step S1 and the diacolated extraction powder obtained in the step S2 with superfine silica powder to obtain a total mixture;
s4, filling the Chinese patent medicine: and filling the S3 total mixture into a capsule to obtain the cicada itching relieving composition capsule.
The beneficial effects are that: the scheme firstly carries out supercritical extraction on the mixed medicinal materials, and utilizes the advantages of rectification and liquid-liquid extraction combined with the supercritical extraction to fully extract medicinal components in the mixed medicinal materials; and percolating the crude extract residue obtained by supercritical extraction to further extract medicinal components in the residue, thereby improving the content of medicinal components in the extracted medicinal powder. In addition, the supercritical extraction and the percolation extraction adopted in the scheme are low-temperature extraction processes, so that the phenomena that the structure of the medicinal components is damaged, compatibility is generated and the like in high-temperature extraction are effectively avoided, and the effective content of the medicinal components is reduced; and the medicine powder obtained by extraction has no solvent residue, so that the problems of reduced medicine effect and medication safety caused by the solvent residue in the existing extraction method are effectively avoided.
In addition, the mode of combining the supercritical extraction and the percolation extraction with the micro silica gel is adopted in the scheme, and the compatibility of the supercritical extraction powder and the percolation extraction powder with the micro silica gel is improved in a specific mode, so that more ideal flow-assisting and moisture-proof effects can be exerted, the fluidity and the moisture absorption effect of the capsule powder are improved, and the product meeting the standard requirements is prepared.
Preferably, in S1, the parameters of the supercritical extraction are set as follows: the temperature of the extraction kettle is 36-40 ℃ and the pressure is 22-25 MPa; the flow rate is 100-120L/h; the extraction time is 2-3 hours.
The beneficial effects are that: the proposal carries out supercritical extraction under the condition, can effectively improve the content of the marking components obtained by extraction, for example, the berberine hydrochloride content is 3.3-3.7 mg/granule, the baicalin content is 20.8-21.6 mg/granule, and the content is obviously higher than the minimum standard of the marking components of the cicada itching relieving capsule in the Chinese pharmacopoeia of 2020 edition (berberine hydrochloride is not lower than 0.4 mg/granule and baicalin is not lower than 4.6 mg/granule). The applicant has also found that when supercritical extraction is performed at a temperature below 36 ℃ the content of the marker component obtained is significantly reduced (e.g. berberine hydrochloride content of 2.9 mg/granule, baicalin content of 18.4 mg/granule, and geniposide content of comparative example 1 is relatively reduced). The reason is that when the temperature of the extraction kettle is too low, the solubility of the medicinal components in the mixed medicinal materials is reduced, so that the content of the marked components obtained by extraction is obviously reduced, the medicinal effect of the medicinal powder is reduced, and the reduction of the content of the marked components in the medicinal powder obtained by extraction cannot be compensated even if the extraction time is prolonged.
Preferably, in S2, the diacolation extraction is to take the primary extraction slag obtained in S1, add 60% -75% ethanol solution with the dosage of 2-3 times of the primary extraction slag to moisten the primary extraction slag to form a moistened material; transferring the wet materials into a percolating tank, sealing and placing, adding 60% -75% ethanol solution to submerge the residues, percolating and extracting at the speed of 1-3ml/min/kg of medicinal materials, adding percolating solvent at any time until the medicinal materials are submerged, and collecting percolate which is 20-24 times of the total amount of the medicinal materials.
The beneficial effects are that: the scheme adopts the parameter setting of the percolation extraction, so that the content of the marking component can be obviously improved. However, when too low an ethanol solution concentration (e.g., 50% ethanol solution as in comparative example 5) and too high a percolation rate (e.g., 4ml/min/kg as in comparative example 8) were employed, the content of the marker component in the final product was significantly reduced.
Preferably, in S2, the concentration process is: concentrating the percolate under reduced pressure to obtain concentrated ointment with the relative density of 1.15-1.25.
Preferably, in S2, the lyophilization process is performed as follows: pre-freezing for 2-4 h at-25 to-15 ℃, then heating to-6 to-3 ℃ at a speed of 1.5 to 2.5 ℃/h, and then freeze-drying for 2-4 h; heating to 0 ℃ at the speed of 1.5 ℃/h to 2.5 ℃/h, and then freeze-drying for 8h to 12h; finally, heating to 30-40 ℃ at the speed of 4-5 ℃/h, and then drying for 3-5 h; the vacuum degree is maintained at 140-190 mu Torr in the whole freeze-drying process.
The beneficial effects are that: by adopting the gradient dynamic drying condition, the fluidity, hygroscopicity and the like of the medicinal powder can be ensured to meet the standard requirements. The conventional drying method (such as comparative example 9) and the freeze-drying method lacking gradient (such as comparative example 11 lacking the 0 ℃ for 8-12 h stage) are adopted, and the drying is not continued after the freeze-drying treatment (such as comparative example 10 lacking the 30-40 ℃ for 3-5 h stage), so that the obtained medicinal powder is treated in such a way, and the capsule product meeting the requirements of fluidity and hygroscopicity cannot be obtained.
Preferably, in the step S3, the dosage of the micro powder silica gel is 2-3% of the total mass of the supercritical extraction powder and the percolation extraction powder.
The beneficial effects are that: by adopting the micro silica gel with the quality as the pharmaceutic adjuvant, the content of the marking components in the total mixture can be effectively ensured to be at a higher level, the fluidity of the total mixture can be improved, the hygroscopicity can be reduced, and the capsule filling quantity difference is small. The applicant has found that if the aerosil is replaced by talc (e.g. comparative example 12) or magnesium stearate (e.g. comparative example 13), the flowability and hygroscopicity of the resulting total mixture are affected, making the drug susceptible to moisture failure.
Preferably, in S2, the particle sizes of the supercritical extraction powder and the percolation extraction powder are obtained by sieving with a 80-100 mesh sieve.
Preferably, in the step S3, the mixing is to add the supercritical extraction powder, the diacolated extraction powder and the micro powder silica gel into a three-dimensional motion mixer, and mix for 5-10 min to obtain the total mixture.
Detailed Description
The present invention will be described in further detail with reference to examples, but embodiments of the present invention are not limited thereto. Unless otherwise indicated, the technical means used in the following examples and experimental examples are conventional means well known to those skilled in the art, and the materials, reagents and the like used are all commercially available. The technical means used in the following examples are conventional means well known to those skilled in the art unless otherwise indicated.
Example 1:
the scheme provides a cicada itching relieving composition capsule for improving the content of a marking component, and the raw material formula is shown in table 1.
Table 1: raw material formula of cicada antipruritic composition capsule
The scheme also provides a preparation method of the cicada itching-relieving composition capsule for improving the content of the marking components, which comprises the following steps:
s1, preparing supercritical extraction medicinal powder: mixing the raw materials according to the parts by weight, namely honeysuckle, gardenia, baical skullcap root, lightyellow sophora root, amur corktree bark, dahurian angelica root, gentian, cortex dictamni, common cnidium fruit, belvedere fruit, weeping forsythiae capsule, cicada slough, patchouli, rehmannia root, sweet wormwood herb and liquoric root, crushing, sieving with a 20-mesh sieve to obtain crude powder, and carrying out supercritical extraction on the crude powder for 3 times at the temperature of 37 ℃ and the pressure of 24MPa, wherein the extraction time is 2.5h each time, and the carbon dioxide flow is 110L/h (kg/h). Collecting and combining the extracts obtained by 3 times of extraction to obtain a mixed extract, concentrating under reduced pressure to obtain solid substances, pulverizing, and sieving with 80 mesh sieve to obtain supercritical extract powder for use. The residue after supercritical extraction remains for subsequent process flows, hereinafter referred to as primary extraction residue. In the present technical solution, conditions for supercritical carbon dioxide extraction may be selected as follows:
the temperature of the extraction kettle is 36-40 ℃ (preferably 36-38 ℃) and the pressure is 22-25 MPa; the flow rate of the carbon dioxide is 100-120L/h; the extraction time is 2-3 hours.
In this scheme, the formulation (shown in table 1) within the above range of raw materials is suitable for use in the method, and is a specific display scheme effect, and only one specific formulation is adopted for subsequent process study. For reference, the raw materials used in this example are as follows: 350 parts of honeysuckle, 350 parts of gardenia, 350 parts of radix scutellariae, 350 parts of radix sophorae flavescentis, 250 parts of cortex phellodendri, 350 parts of radix angelicae, 250 parts of gentian, 350 parts of cortex dictamni, 350 parts of fructus cnidii, 350 parts of fructus kochiae, 350 parts of fructus forsythiae, 150 parts of periostracum cicada, 350 parts of herba pogostemonis, 550 parts of rehmannia, 550 parts of sweet wormwood and 250 parts of liquorice.
S2, preparing diacolated extract powder: percolating and extracting the primary extraction residues obtained in the step S1 to obtain percolate, concentrating, lyophilizing and pulverizing to obtain percolate extract powder.
Specifically, in S2, the primary extraction residues are taken, 3 times of ethanol solution with the volume percentage of 70 percent of the medicinal materials (60% -75% of ethanol solution with the dosage of 2-3 times can be selected) is added, and the mixture is fully stirred and wetted to form a wetting material; transferring the wet materials into a percolating tank, sealing and placing for 4 hours (3-4 hours are selected), adding 70% ethanol solution (60% -75% ethanol solution is selected) to submerge the residues, percolating and extracting at the speed of 2ml/min/kg of medicinal materials (1-3 ml/min/kg of medicinal materials is selected), adding percolating solvent at any time to submerge the medicinal materials, and collecting percolate (the percolate is specifically collected for 24 times of the total amount of medicinal materials in the embodiment) of 20-24 times of the total amount of medicinal materials.
The concentration treatment is as follows: recovering ethanol from the percolate under reduced pressure, and concentrating under reduced pressure to obtain concentrated ointment with relative density of 1.15-1.25.
The freeze-drying treatment comprises the following steps: and adding the concentrated ointment into a drying tray with thickness of no more than 1cm, and lyophilizing. The procedure for lyophilization treatment was: pre-freezing at-20 ℃ for 3 hours, then heating to-5 ℃ at a speed of 2 ℃/h, and then freeze-drying for 3 hours; heating to 0 ℃ at a speed of 2 ℃/h, and freeze-drying for 10h; finally, heating to 35 ℃ at a speed of 5 ℃/h, and then drying for 4h to obtain freeze-dried medicinal powder; the vacuum degree is maintained at 140-190 mu Torr in the whole freeze-drying process. In the actual operation process, the lyophilization procedure can be selected under the following conditions, and all the conditions can obtain the ideal effects:
pre-freezing for 2-4 h at-25 to-15 ℃, then heating to-6 to-3 ℃ at a speed of 1.5 to 2.5 ℃/h, and then freeze-drying for 2-4 h; heating to 0 ℃ at the speed of 1.5 ℃/h to 2.5 ℃/h, and then freeze-drying for 8h to 12h; finally, heating to 30-40 ℃ at the speed of 4-5 ℃/h, and then drying for 3-5 h; the vacuum degree is maintained at 140-190 mu Torr in the whole freeze-drying process. And finally, crushing the freeze-dried medicinal powder, and sieving the crushed powder with a 80-mesh sieve to obtain diacolated medicinal powder for standby.
S3, preparing a total mixture: adding the above supercritical extraction powder and diacolation extraction powder and micropowder silica gel with 2.5% of total mass of both (alternatively micropowder silica gel with 2-3% of total mass of supercritical extraction powder and diacolation extraction powder) into three-dimensional motion mixer, and mixing for 5-10 min to obtain total mixture (in this embodiment, mixing for 10 min).
S4, filling the Chinese patent medicine: and (3) filling the S3 total mixture into capsules, and filling 0.5g of each capsule to obtain the cicada itching relieving capsules.
Example 2
The present example is basically the same as example 1 except that in S1, the crude drug powder is subjected to supercritical extraction 3 times at 38 ℃ under 22MPa pressure for 3 hours each time, otherwise the same as example 1.
Example 3
The present example is basically the same as example 1 except that in S1, the crude drug powder is subjected to supercritical extraction at 36 ℃ and 25MPa pressure for 3 times each for 2 hours, otherwise the same as example 1.
Example 4
This example is basically the same as example 1, except that in S2, the percolation medium is a 60% ethanol solution.
Example 5
This example is basically the same as example 1, except that in S2, the percolating medium is a 75% ethanol solution.
Example 6
This example is basically the same as example 1, except that in S2, the percolation rate is 1ml/min/kg of ethanol solution.
Example 7
This example is basically the same as example 1, except that in S2, the percolation rate is 3ml/min/kg of ethanol solution.
Comparative example 1
This comparative example is basically the same as example 1, except that the supercritical extraction conditions are changed in S1: the extraction temperature was 33℃and the extraction time was 4 hours each time, and the other operation was the same as in example 1, except that the content of berberine and baicalin was reduced and the content of gardenoside was relatively reduced in the obtained final product.
Comparative example 2
This comparative example is basically the same as example 1, except that the supercritical extraction conditions are changed in S1: the extraction temperature was 40℃and each extraction was carried out for 2.5 hours, in the same manner as in example 1, but the marking composition in the obtained finished product was not much changed from that in example 1.
Comparative example 3
The comparative example is basically the same as example 1, except that the above raw materials are mixed with honeysuckle, gardenia, baikal skullcap root, kuh-seng, phellodendron bark, dahurian angelica root, gentian root, dittany bark, cnidium fruit, belvedere fruit, weeping forsythia, cicada slough, patchouli, rehmannia root, sweet wormwood and licorice according to parts by weight, the raw materials are crushed and sieved by a 40-mesh sieve to obtain coarse powder, and the coarse powder is subjected to supercritical extraction to obtain supercritical extracted medicinal powder for standby. The comparative example is to crush crude powder of medicinal materials into finer powder, the content of the marked components (berberine hydrochloride and baicalin) in the cicada antipruritic composition capsule is not obviously improved, but the crushing energy consumption of the medicinal materials is increased, and in the subsequent percolation extraction process, due to the fact that the medicinal residues are too fine, percolate is very difficult, and the production continuity is affected.
Comparative example 4
The comparative example is basically the same as example 1, except that the above raw materials are mixed with honeysuckle, gardenia, baikal skullcap root, kuh-seng, phellodendron bark, dahurian angelica root, gentian root, dittany bark, cnidium fruit, belvedere fruit, weeping forsythia, cicada slough, patchouli, rehmannia root, sweet wormwood and licorice according to parts by weight, the raw materials are crushed and sieved by a 10-mesh sieve to obtain coarse powder, and the coarse powder is subjected to supercritical extraction to obtain supercritical extracted medicinal powder for standby. In the comparative example, crude drug powder is crushed into coarser powder, however, after supercritical extraction and diacolation extraction, the content of the marked components (berberine hydrochloride and baicalin) in the capsule of the obtained cicada antipruritic composition is obviously reduced, so that the curative effect of the capsule is reduced.
Comparative example 5
The comparative example is basically the same as example 1, except that the percolating medium is 50% ethanol solution, and the contents of berberine hydrochloride and baicalin in the finished product are reduced.
Comparative example 6
The comparative example is basically the same as example 1, except that the percolating medium is 80% ethanol solution, and the content of berberine hydrochloride and baicalin in the finished product is not obviously different from that in example 1, however, the concentration of the percolating medium is increased, and the production cost is increased.
Comparative example 7
The comparative example is basically the same as example 1, except that the percolation speed is 0.5ml/min/kg, and the contents of berberine hydrochloride and baicalin in the finished product are increased, but the production time is too long, which is unfavorable for improving the production efficiency.
Comparative example 8
This comparative example is basically the same as example 1, except that the percolation rate is 4ml/min/kg, and the contents of berberine hydrochloride and baicalin are reduced due to too fast percolation.
Comparative example 9
This comparative example is substantially the same as example 1, except that the procedure for the lyophilization process is:
freeze-drying at constant temperature of-5 ℃ for 16h, and then drying at 35 ℃ for 4h to obtain freeze-dried medicinal powder, wherein the vacuum degree is maintained at 140-190 mu Torr in the whole freeze-drying process.
The present comparative example, in which the percolated extract obtained in S2 was subjected to constant temperature lyophilization treatment, resulted in an improvement of about 66% in hygroscopicity of the total mixture and the filler in the capsule (this comparative example is compared to example 1). This means that the lyophilization process has a very large impact on the hygroscopicity of the drug, and only by using a special lyophilization process, the quality of the drug can be ensured, avoiding quality changes due to too fast moisture absorption of the drug. In addition, the lyophilization process of this comparative example also resulted in poor flowability of the total mixture, resulting in a difference in the loading.
Comparative example 10
This comparative example is substantially the same as example 1, except that the procedure for the lyophilization process is:
pre-freezing at-20 ℃ for 3 hours, then heating to-5 ℃ at a speed of 2 ℃/h, and then freeze-drying for 3 hours; and then heating to 0 ℃ at the speed of 2 ℃/h, then freeze-drying for 20h, and drying at the temperature of 35 ℃ to obtain freeze-dried powder, wherein the vacuum degree is maintained at 140-190 mu Torr in the whole freeze-drying process.
The total mixture was subjected to gradient freeze-drying in this comparative example, but the total mixture obtained and the filler in the capsule had improved hygroscopicity by about 60% without being subjected to high-temperature 35 ℃ drying after freeze-drying (this comparative example is relative to example 1). This means that the combination of the lyophilization process and the high temperature drying process is very critical to improve the moisture absorption resistance of the powder, and the lyophilization process alone cannot effectively improve the moisture absorption resistance, so that the quality of the drug may be affected due to the excessively rapid moisture absorption. In addition, the lyophilization process of this comparative example also resulted in poor flowability of the total mixture, resulting in a difference in the loading.
The inventors have also tried to dry the percolated extract obtained in S2 conventionally (30 ℃), but the experimental results found that the percentage of hygroscopic weight gain of the total mixture and the filler in the capsule reached 6% or more, regardless of whether the inventors shortened or prolonged the drying time to control the water content of the powder (experimental method refer to experimental example 1).
Comparative example 11
This comparative example is substantially the same as example 1, except that the procedure for the lyophilization process is:
pre-freezing at-20 ℃ for 3 hours, then heating to-5 ℃ at a speed of 2 ℃/h, and then freeze-drying for 15 hours; finally, heating to 35 ℃ at a speed of 5 ℃/h, and then drying for 4h to obtain freeze-dried medicinal powder; the vacuum degree is maintained at 140-190 mu Torr in the whole freeze-drying process.
In this comparative example, although gradient freeze-drying was used, the freeze-drying procedure was different from example 1 (the present solution did not use a gradient of freeze-drying at 0 ℃), and the hygroscopicity of the obtained total mixture and the filler in the capsule was improved. This illustrates that a particular lyophilization procedure is critical to ensure that the product is stored for long periods of time or in environments with high air humidity. In addition, the lyophilization process of this comparative example also resulted in poor flowability of the total mixture, resulting in a difference in the loading.
Comparative example 12
The comparative example was basically the same as example 1, except that talc powder of equal mass was used instead of silica fume. Talc as a glidant can result in poor flowability of the total blend, resulting in loading differences. In addition, the hygroscopicity of the total mixture is affected, making the drug vulnerable to moisture.
Comparative example 13
The comparative example is basically the same as example 1, except that the use of magnesium stearate with equal mass instead of the colloidal silica fume also resulted in poor flowability of the total mixture and an increase in hygroscopicity of the total mixture, and specifically, compared with example 1, the hygroscopicity of the total mixture in the comparative example was improved by about 81%.
Comparative example 14
The comparison is basically the same as in example 1, except that the implementation of this comparison is performed with reference to the relevant regulations of the "Chinese pharmacopoeia" 1481 cicada antipruritic capsule. The method comprises the following steps:
the formulation of this comparative example was identical to example 1, and the preparation method of this comparative example was: adding water 8 times of herba Agastaches, flos Lonicerae, fructus forsythiae, radix Angelicae Dahuricae, and herba Artemisiae Annuae into the above sixteen materials, extracting volatile oil for 8 hr, and collecting distilled water solution in another container; decocting the residues and the rest of radix Scutellariae and other materials in water for three times (2 hours for the first time, 1 hour for the second and third times respectively), mixing decoctions, filtering, mixing the filtrate with the distilled water solution, concentrating to obtain fluid extract with relative density of 1.20-1.22 (80deg.C), adding appropriate amount of starch, granulating, drying, adding the volatile oil and peppermint oil of herba Agastaches, mixing, encapsulating, and making into 1000 capsules. By adopting the preparation method, the contents of berberine hydrochloride and baicalin in the finished product are obviously reduced, and the total mixture for encapsulating has increased hygroscopicity and poor fluidity.
Comparative example 15
On the basis of comparative example 14, the hygroscopicity of the total mixture for encapsulation was not improved compared with comparative example 14 by adding 2.5% by mass of the fine silica gel powder, and was almost identical in hygroscopicity value to comparative example 14. This demonstrates that the silica fume only provides an optimum effect on the hygroscopicity of the total mixture for a particular material composition (e.g., examples 1-7). The inventor analyzes that the reason is that the proposal adopts the combination mode of supercritical extraction and freeze-drying treatment, and the specific mode ensures that the compatibility of the supercritical extraction powder and the percolation extraction powder with the micro silica gel is improved, thereby playing a more ideal role of flow assistance and moisture prevention.
Experimental example 1: examples and comparative examples quality inspection
The detection standard is specifically as follows (refer to relevant regulations of the "Chinese pharmacopoeia" 1481 cicada antipruritic capsule:
[ PROBLEMS ] the product is hard capsule, and the content is brown yellow to brown granule or powder; fragrant smell and bitter taste.
Identification of geniposide, berberine hydrochloride, sophora flavescens, scutellaria baicalensis and Artemisia annua L
(1) Taking 5g of the content of the product, adding 30ml of water to dissolve, filtering, extracting the filtrate with diethyl ether for 2 times by shaking, removing diethyl ether liquid each time by 20ml, adjusting the pH value of the water liquid to 8-9 by using sodium hydroxide test solution, extracting with n-butanol for 3 times by shaking, 10ml each time, combining n-butanol liquid, washing with 0.1mol/L sodium hydroxide solution for 2 times, 10ml each time, removing sodium hydroxide solution, recovering solvent from n-butanol liquid to dryness, adding 1ml of methanol into residues to dissolve, and taking the residues as test solution. Adding methanol into the gardenoside reference substance to obtain a solution containing 2mg per 1ml, and taking the solution as reference substance solution. According to thin layer chromatography (rule 0502), 10 μl of each of the above two solutions is absorbed and respectively spotted on the same silica gel G thin layer plate, n-butanol-acetic acid-water (6:2:0.25) is used as developing agent, and then developed, taken out, air dried, sprayed with 5% vanillin sulfuric acid solution, and heated until the spots develop clearly. Spots of the same color appear in the sample chromatogram at positions corresponding to those of the control chromatogram.
(2) Taking 5g of the content of the product, adding 30ml of water to dissolve, filtering, adding 0.3ml of concentrated ammonia solution into the filtrate, shaking and extracting for 3 times with dichloromethane, 10ml each time, mixing the extracting solutions, recovering the solvent to dryness, and adding 1ml of methanol into the residue to dissolve, thereby obtaining the solution of the sample. And adding methanol into berberine hydrochloride as reference substance to obtain solution containing 0.1mg per 1 ml. According to thin layer chromatography (rule 0502), 10 μl of each of the above two solutions was absorbed, spotted on the same silica gel G thin layer plate, and developed with n-butanol-acetic acid-water (6:2:0.25) as developing agent, taken out, air dried, and inspected under ultraviolet lamp (365 nm). The sample chromatogram showed the same yellow fluorescent spot at the position corresponding to the control chromatogram.
(3) Taking 0.5g of radix sophorae flavescentis reference medicine, adding 0.3ml of concentrated ammonia test solution and 25ml of dichloromethane, shaking and extracting for 4 hours, filtering, recovering the solvent from the filtrate until the solvent is dry, and adding 1ml of methanol into the residue to dissolve the solvent to obtain a reference medicine solution. According to the thin layer chromatography (general rule 0502), 10 μl of the sample solution under (identification) item (2) and 10 μl of the control medicinal solution are respectively spotted on the same silica gel G thin layer plate, and the toluene-acetone-ethyl acetate-concentrated ammonia solution (2:3:4:0.2) is used as developing agent, and the solution is developed, taken out, dried and sprayed with dilute bismuth potassium iodide solution. Spots of the same color appear on the chromatogram of the test sample at positions corresponding to those of the chromatogram of the control drug.
(4) Taking 5g of the content of the product, adding 30ml of ethanol, heating and refluxing for 20 minutes, filtering, evaporating filtrate to dryness, and adding 1ml of ethanol into residues to dissolve the residues to obtain a sample solution. And adding 20ml of ethanol into 1g of radix Scutellariae control medicinal material, and preparing into a medicinal material solution by the same method. According to thin layer chromatography (general rule 0502), sucking 5 μl of each of the above two solutions, respectively spotting on the same silica gel G thin layer plate, spreading with dichloromethane-methanol-formic acid (7:1:0.5) as developing agent, taking out, air drying, spraying 2% ferric trichloride ethanol solution, and inspecting in sunlight. Spots of the same color appear on the chromatogram of the test sample at positions corresponding to those of the chromatogram of the control drug.
(5) 5g of the product is taken, 30ml of ethyl acetate is added, heating reflux is carried out for 30 minutes, filtration is carried out, and the filtrate is concentrated to 1ml to be taken as a test sample solution. 1g of sweet wormwood herb reference medicine is additionally taken, 20ml of ethyl acetate is added, and the preparation method is carried out in the same way to obtain a reference medicine solution. According to thin layer chromatography (general rule 0502), 5 μl of each of the above two solutions was sucked and spotted on the same silica gel G thin layer plate, and the mixture was developed with dichloromethane-diethyl ether (2:1) as developing agent, taken out, dried, and inspected under ultraviolet lamp (365 nm). In the chromatogram of the test sample, fluorescent spots with the same color appear at the positions corresponding to the chromatogram of the control medicinal material.
[ MEANS FOR SOLVING ] the following regulations (general rule 0103) should be satisfied.
[ measurement of the content of berberine hydrochloride and baicalin ]
(1) Berberine hydrochloride: the measurement was performed by high performance liquid chromatography (general rule 0512).
(1.1) chromatographic conditions and System applicability test: octadecylsilane chemically bonded silica is used as a filler; methanol-acetonitrile-water (50:20:30) (0.1% sodium dodecyl sulfate and 0.1% phosphoric acid solution) was used as mobile phase; the detection wavelength is 265nm, and the theoretical plate number is not less than 5000 according to berberine hydrochloride peak.
(1.2) preparation of control solution: taking a proper amount of berberine hydrochloride reference substance, precisely weighing, adding 60% methanol to prepare a solution containing 5 mug per 1 ml.
(1.3) preparation of a test sample solution: taking the content of the product under different loading differences, grinding, taking 0.25g, precisely weighing, placing into a conical flask with a plug, precisely adding 50ml of 60% methanol, weighing, performing ultrasonic treatment (power 200W, frequency 40 kHz) for 30 minutes, cooling, weighing again, supplementing the lost weight with 60% methanol, shaking uniformly, filtering, and taking subsequent filtrate.
(1.4) assay: respectively precisely sucking 20 μl of the reference solution and the sample solution, and injecting into a liquid chromatograph for measurement.
Each granule contains cortex Phellodendri and berberine hydrochloride (C) 20 H 17 NO 4 HCl) is not less than 0.4mg.
(2) Radix Scutellariae Baicalensis: the measurement was performed by high performance liquid chromatography (general rule 0512).
(2.1) chromatographic conditions and System applicability test: octadecylsilane chemically bonded silica is used as a filler; methanol-water-phosphoric acid (44:56:0.2) is used as a mobile phase; the detection wavelength is 280nm, and the theoretical plate number is not lower than 2500 calculated according to baicalin peak.
(2.2) preparation of control solution: taking appropriate amount of baicalin reference substance, precisely weighing, and adding methanol to obtain solution containing 20 μg per 1 ml.
(2.3) preparation of a test sample solution: taking the content of the product under different loading differences, grinding, taking 1g, precisely weighing, placing in a conical flask with a plug, precisely adding 50ml of 70% ethanol, weighing, performing ultrasonic treatment (power 200W, frequency 40 kHz) for 30 minutes, cooling, weighing again, supplementing the reduced weight with 70% ethanol, shaking uniformly, filtering, precisely measuring 1ml of subsequent filtrate, placing in a measuring flask with 10ml, adding methanol to scale, shaking uniformly, filtering, and taking the subsequent filtrate.
(2.4) assay: respectively precisely sucking 10 μl of the reference solution and the sample solution, and injecting into a liquid chromatograph for measurement.
Each granule contains baicalin (C) and baicalin 21 H 18 O 11 ) And not less than 4.6mg.
The test procedure referred to the following steps:
(1) The dried glass weighing bottle with plug (with the outer diameter of 50mm and the height of 15 mm) is taken, placed in a proper constant temperature dryer (with ammonium chloride or ammonium sulfate saturated solution placed at the lower part) or a climatic chamber (with the set temperature of 25 ℃ +/-1 ℃ and the relative humidity of 80% +/-2%) at 25 ℃ +/-1 ℃ for one day before the test, and precisely weighed (m 1 )。
(2) Spreading appropriate amount of sample (powder in capsule) in the weighing bottle, wherein the thickness of sample is about 1mm, and precisely weighing (m 2 )。
(3) The weighing bottle is opened and placed under the constant temperature and humidity condition for 24 hours together with the bottle cap.
(4) The lid of the weighing flask was closed, and the weight (m 3 )。
The cicada antipruritic composition capsules obtained in the examples and comparative examples were taken and the measurement results are shown in the following tables (tables 2 to 5):
table 2: examples 1 to 3 reference quality Standard test results
Table 3: examples 4 to 7 reference quality Standard test results
Table 4: comparative examples 1, 2, 4 to 8 reference quality Standard test results
/>
Table 5: comparative examples 9 to 15 reference quality Standard test results
/>
The inventor encounters the following technical difficulties in producing the cicada antipruritic capsule: the content of the marking component in the capsule is low; the finished traditional Chinese medicine powder has poor fluidity and strong hygroscopicity (easy moisture absorption), and the powder is easy to absorb moisture to further obstruct the fluidity of the powder, so that continuous production cannot be smoothly carried out; and the easy moisture absorption of the medicine also affects the quality of the product after long-term storage or storage in a humid environment.
The inventors have studied the cause of the above phenomena and tried various means to solve the above problems, and finally found the cause of the non-ideal content of the marker ingredient in the powder as follows: the method comprises the steps of selecting a medicine powder extraction mode, a medicine powder freeze-drying mode and a medicine powder auxiliary material. Referring to tables 2 to 5 and examples and comparative examples, in terms of the extraction mode of the powder, the powder and the filled capsule were obtained by the conventional extraction method (comparative example 14), the contents of berberine hydrochloride and baicalin in the finished product were low, and the hygroscopicity of the total mixture for filling the capsule was increased. Although the combination of supercritical extraction and percolation extraction can raise the content of the marker component in the powder to some extent, if proper supercritical extraction temperature, mesh number of medicinal materials, concentration of percolation solvent and percolation speed are not selected, the content of the marker component in the powder is still reduced. For example, the inventors tried lower supercritical extraction temperature (33 ℃ C. In comparative example 1), lower mesh size of the medicinal material (10 mesh size of the medicinal material in comparative example 4), too low concentration of the percolation solvent (50% ethanol solution in comparative example 5), too fast percolation rate (4 ml/min/kg percolation rate in comparative example 8), and could not obtain medicinal powder with higher content of the marker ingredient. In the aspect of the freeze-drying mode of the medicinal powder, the traditional drying method (such as comparative example 9) and the freeze-drying method lacking gradient (such as comparative example 11 lacking the 0 ℃ for 8-12 h stage) are adopted, and the drying is not continued after the freeze-drying treatment (such as comparative example 10 lacking the 30-40 ℃ for 3-5 h stage), so that the obtained medicinal powder can not obtain capsule products meeting the requirements of fluidity and hygroscopicity. In the aspect of selecting medicinal powder auxiliary materials, if the superfine silica powder is replaced by talcum powder (such as comparative example 12) or magnesium stearate (such as comparative example 13), the fluidity and hygroscopicity of the obtained total mixture are affected, so that the medicine is easy to be affected by damp and lose efficacy. However, if the powder is prepared by adopting the traditional high-temperature extraction and the traditional drying process, even if the micro powder silica gel accounting for 2.5% of the total amount of the fluid extract is mixed with the powder, the fluidity and hygroscopicity of the obtained total mixture still cannot meet the standard requirements (the micro powder silica gel in the comparison document 15 cannot effectively improve the anti-hygroscopicity of the product); the inventor analyzes that the reason is that the proposal adopts the combination mode of supercritical extraction and freeze-drying treatment, and the specific mode ensures that the compatibility of the supercritical extraction powder and the percolation extraction powder with the micro silica gel is improved, thereby playing a more ideal role of flow assistance and moisture prevention.
In summary, examples 1-7 demonstrate that the cicada itching-relieving composition particles prepared by the supercritical extraction and diacolation extraction combined freeze-drying mode and the micro silica gel of the scheme meet the requirements of related standards on the flowability and hygroscopicity of the total mixture. The berberine hydrochloride content in the capsule prepared by the scheme is 3.3-3.7 mg/granule, the baicalin content is 20.8-21.6 mg/granule, and the content is obviously higher than the minimum standard of the marked component content of the cicada itching relieving capsule in the Chinese pharmacopoeia 2020 edition (berberine hydrochloride is not lower than 0.4 mg/granule and baicalin is not lower than 4.6 mg/granule), thereby effectively improving the quality and the drug effect of the medicine. In addition, the supercritical extraction and the percolation extraction are adopted in the scheme, large-scale energy consumption is not required in the preparation stage, and the preparation method is environment-friendly, the production efficiency is greatly improved, and the production cost is greatly reduced. In addition, the medicine of the scheme only comprises the superfine silica gel powder and the medicinal material extract, and the dosage of auxiliary materials for the traditional Chinese medicine is reduced, so that the risk of stress reaction when a patient takes the medicine is obviously reduced, and the safety of the medicine is improved.
The foregoing is merely exemplary of the present invention, and specific technical solutions and/or features that are well known in the art have not been described in detail herein. It should be noted that, for those skilled in the art, several variations and modifications can be made without departing from the technical solution of the present invention, and these should also be regarded as the protection scope of the present invention, which does not affect the effect of the implementation of the present invention and the practical applicability of the patent. The protection scope of the present application shall be subject to the content of the claims, and the description of the specific embodiments and the like in the specification can be used for explaining the content of the claims.
Claims (6)
1. An cicada itching relieving composition capsule for improving the content of a marking component is characterized in that: the raw materials of the medicine comprise 350 to 450 parts of honeysuckle, 350 to 450 parts of gardenia, 350 to 450 parts of baical skullcap root, 350 to 450 parts of lightyellow sophora root, 250 to 350 parts of amur corktree bark, 350 to 450 parts of dahurian angelica root, 250 to 350 parts of gentian, 350 to 450 parts of dittany bark, 350 to 450 parts of common cnidium fruit, 350 to 450 parts of belvedere fruit, 350 to 450 parts of weeping forsythiae capsule, 150 to 250 parts of cicada slough, 350 to 450 parts of patchouli, 550 to 650 parts of rehmannia root, 550 to 650 parts of sweet wormwood and 250 to 350 parts of liquorice;
the preparation method comprises the following steps:
s1, preparing supercritical extraction medicinal powder: mixing medicinal materials of honeysuckle, gardenia, radix scutellariae, radix sophorae flavescentis, cortex phellodendri, radix angelicae, gentian, cortex dictamni, fructus cnidii, fructus kochiae, fructus forsythiae, periostracum cicada, herba pogostemonis, rehmannia glutinosa, sweet wormwood and liquorice, crushing and sieving to obtain coarse medicinal material powder with 16-20 meshes, extracting the coarse medicinal material powder for 3 times by supercritical extraction to obtain primary extracted medicinal powder and primary extracted medicinal residues, crushing and sieving the primary extracted medicinal powder to obtain supercritical extracted medicinal powder; the parameters of the supercritical extraction are set as follows: the temperature of the extraction kettle is 36-40 ℃ and the pressure is 22-25 MPa; the flow rate is 100-120L/h; the extraction time is 2-3 hours;
s2, preparing diacolated extract powder: adding 60% -75% ethanol solution with 2-3 times of the feeding amount of the primary extraction residues to infiltrate the primary extraction residues to form a wetting material; transferring the wet materials into a percolating tank, sealing and placing, adding 60% -75% ethanol solution to submerge the residues, percolating and extracting at the speed of 1-3ml/min/kg of medicinal materials, adding percolating solvent at any time until the medicinal materials are submerged, and collecting percolate which is 20-24 times of the total amount of the medicinal materials;
concentrating, lyophilizing and pulverizing the percolate to obtain percolate extract powder; the freeze-drying treatment comprises the following procedures: pre-freezing for 2-4 h at-25 to-15 ℃, then heating to-6 to-3 ℃ at a speed of 1.5 to 2.5 ℃/h, and then freeze-drying for 2-4 h; heating to 0 ℃ at the speed of 1.5 ℃/h to 2.5 ℃/h, and then freeze-drying for 8h to 12h; finally, heating to 30-40 ℃ at the speed of 4-5 ℃/h, and then drying for 3-5 h; the vacuum degree is maintained at 140-190 mu Torr in the whole freeze-drying process;
s3, preparing a total mixture: mixing the supercritical extraction powder obtained in the step S1 and the diacolated extraction powder obtained in the step S2 with superfine silica powder to obtain a total mixture;
s4, filling the Chinese patent medicine: and (3) filling the total mixture obtained in the step (S3) into capsules to obtain the cicada itching-relieving composition capsules.
2. The method for preparing the cicada itching relieving composition capsule for improving the content of the marking components according to claim 1, which is characterized in that: the method comprises the following steps:
s1, preparing supercritical extraction medicinal powder: the method comprises the steps of mixing raw materials including honeysuckle, gardenia, radix scutellariae, radix sophorae flavescentis, cortex phellodendri, radix angelicae, gentian, cortex dictamni, fructus cnidii, fructus kochiae, fructus forsythiae, periostracum cicada, patchouli, rehmannia glutinosa, sweet wormwood and liquorice, crushing and sieving to obtain crude powder of 16-20 meshes, carrying out supercritical extraction on the crude powder of the crude material for 3 times to obtain primary extract powder and primary extract residues, and crushing and sieving the primary extract powder to obtain supercritical extract powder; the parameters of the supercritical extraction are set as follows: the temperature of the extraction kettle is 36-40 ℃ and the pressure is 22-25 MPa; the flow rate is 100-120L/h; the extraction time is 2-3 hours;
s2, preparing diacolated extract powder: adding 60% -75% ethanol solution with 2-3 times of the feeding amount of the primary extraction residues to infiltrate the primary extraction residues to form a wetting material; transferring the wet materials into a percolating tank, sealing and placing, adding 60% -75% ethanol solution to submerge the residues, percolating and extracting at the speed of 1-3ml/min/kg of medicinal materials, adding percolating solvent at any time until the medicinal materials are submerged, and collecting percolate which is 20-24 times of the total amount of the medicinal materials;
concentrating, lyophilizing and pulverizing the percolate to obtain percolate extract powder; the freeze-drying treatment comprises the following procedures: pre-freezing for 2-4 h at-25 to-15 ℃, then heating to-6 to-3 ℃ at a speed of 1.5 to 2.5 ℃/h, and then freeze-drying for 2-4 h; heating to 0 ℃ at the speed of 1.5 ℃/h to 2.5 ℃/h, and then freeze-drying for 8h to 12h; finally, heating to 30-40 ℃ at the speed of 4-5 ℃/h, and then drying for 3-5 h; the vacuum degree is maintained at 140-190 mu Torr in the whole freeze-drying process;
s3, preparing a total mixture: mixing the supercritical extraction powder obtained in the step S1 and the diacolated extraction powder obtained in the step S2 with superfine silica powder to obtain a total mixture;
s4, filling the Chinese patent medicine: and (3) filling the total mixture obtained in the step (S3) into capsules to obtain the cicada itching-relieving composition capsules.
3. The method for preparing the cicada itching relieving composition capsule for improving the content of the marking components according to claim 2, which is characterized in that: in S2, the concentration process is: concentrating the percolate under reduced pressure to obtain concentrated ointment with the relative density of 1.15-1.25.
4. The method for preparing the cicada itching relieving composition capsule for improving the content of the marking components according to claim 2, which is characterized in that: in S3, the dosage of the micro powder silica gel is 2-3% of the total mass of the supercritical extracted medicinal powder and the percolating extracted medicinal powder.
5. The method for preparing the cicada itching relieving composition capsule for improving the content of the marking components according to claim 2, which is characterized in that: in S2, the particle sizes of the supercritical extraction powder and the percolation extraction powder are obtained by sieving with a sieve of 80-100 meshes.
6. The method for preparing the cicada itching relieving composition capsule for improving the content of the marking components according to claim 2, which is characterized in that: in S3, adding the supercritical extraction powder, the diacolation extraction powder and the micro powder silica gel into a three-dimensional motion mixer, and mixing for 5-10 min to obtain a total mixture.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310448644.6A CN116236529B (en) | 2023-04-24 | 2023-04-24 | Cicada itching-relieving composition capsule for improving content of marking components and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310448644.6A CN116236529B (en) | 2023-04-24 | 2023-04-24 | Cicada itching-relieving composition capsule for improving content of marking components and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116236529A CN116236529A (en) | 2023-06-09 |
| CN116236529B true CN116236529B (en) | 2024-02-20 |
Family
ID=86633433
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310448644.6A Active CN116236529B (en) | 2023-04-24 | 2023-04-24 | Cicada itching-relieving composition capsule for improving content of marking components and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116236529B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1843435A (en) * | 2006-02-20 | 2006-10-11 | 重庆希尔安药业有限公司 | Itch-stopping cicada formulation and its preparation method |
-
2023
- 2023-04-24 CN CN202310448644.6A patent/CN116236529B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1843435A (en) * | 2006-02-20 | 2006-10-11 | 重庆希尔安药业有限公司 | Itch-stopping cicada formulation and its preparation method |
Non-Patent Citations (2)
| Title |
|---|
| HPLC法同时测定金蝉止痒胶囊中盐酸小檗碱、黄芩苷和蛇床子素的含量;黄传俊 等;中国药房;第29卷(第12期);1621-1624 * |
| 金蝉止痒颗粒质量标准分析与研究;贾琳等;中国医药导报;第14卷(第22期);42-46 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116236529A (en) | 2023-06-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101579500A (en) | Gynaecologic restorative pharmaceutic preparation and preparation technology and quality control method thereof | |
| CN101396384A (en) | Asiatic centella extract and preparation methode thereof | |
| CN101156907A (en) | A pueraria root scutellaria and coptis extract | |
| CN101057890B (en) | Traditional Chinese medicinal composition for treating coronary heart disease and its preparation method, preparations and its application | |
| CN1739714A (en) | Chinese medicine prepn of invigorating kidney and benefiting vital energy and its prepn process and quality control method | |
| CN1977889A (en) | Medicinal composition of astragalus, salvia miltrorrhiza and oxymatrine, and its preparing method | |
| CN101966316B (en) | Gujin pill pellet and preparation method thereof | |
| CN102920964B (en) | Traditional Chinese medicine preparation for curing cough | |
| CN116236529B (en) | Cicada itching-relieving composition capsule for improving content of marking components and preparation method thereof | |
| CN100485385C (en) | Chinese medicine preparation for nourishing yin and blood, its preparation process and quality control method | |
| CN105521439A (en) | Preparation method of pharmaceutical preparation for promoting blood circulation and removing stasis, diminishing inflammation and relieving pain | |
| CN1679900A (en) | Chinese medicine preparation for treating rheumatosis and arthralgia syndrome making method and quality control thereof | |
| CN100496552C (en) | Chinese medicinal preparation for regulating qi, reducing phlegm, expelling pathologic wind and regulating stomach, and method for preparing the same | |
| CN101785799B (en) | Extract of total triterpenes in dracocephalum moldavica and preparation method and application thereof | |
| CN101422568A (en) | Shen flavor capsule capable of reducing blood sugar and preparation method thereof | |
| CN102048866A (en) | Toxin-expelling face-nourishing pills and preparation method thereof | |
| CN102048929B (en) | Xiaoyukang tablet and preparation method thereof | |
| CN1985946A (en) | New preparing process for lung heat clearing and phlegm resolving preparation | |
| CN100515476C (en) | Compound capsule with pseudo-ginseng and Chinese fanpalm seed, its preparation process and quality control method | |
| CN1739730A (en) | Diabetes treating Chinese medicine prepn and its prepn process and quality control method | |
| CN113827570A (en) | Method for preparing traditional Chinese medicine pellet preparation based on drug carrier technology and application thereof | |
| CN112755092A (en) | Preparation method of angelica sinensis Liuhuang preparation | |
| CN1814007A (en) | Yankening medicine preparation and its preparing method | |
| CN112402515A (en) | Chinese medicinal extract containing insect medicine and preparation method of preparation thereof | |
| CN102048991A (en) | Sugar-reducing comfort pill and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |