CN108210811A - A kind of anaesthetic looks into the preparation method of dry soup pellet and soup mixture - Google Patents
A kind of anaesthetic looks into the preparation method of dry soup pellet and soup mixture Download PDFInfo
- Publication number
- CN108210811A CN108210811A CN201711500256.9A CN201711500256A CN108210811A CN 108210811 A CN108210811 A CN 108210811A CN 201711500256 A CN201711500256 A CN 201711500256A CN 108210811 A CN108210811 A CN 108210811A
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- China
- Prior art keywords
- coarse powder
- elecampane
- pellet
- kaempferia galanga
- decoction
- Prior art date
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- 239000008188 pellet Substances 0.000 title claims abstract description 45
- 235000014347 soups Nutrition 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 239000000203 mixture Substances 0.000 title claims abstract description 24
- 230000003444 anaesthetic effect Effects 0.000 title claims abstract description 17
- 239000000843 powder Substances 0.000 claims abstract description 100
- 239000011248 coating agent Substances 0.000 claims abstract description 31
- 238000000576 coating method Methods 0.000 claims abstract description 31
- 239000000284 extract Substances 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims abstract description 15
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 14
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims abstract description 14
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims abstract description 14
- 239000001116 FEMA 4028 Substances 0.000 claims abstract description 13
- 229960004853 betadex Drugs 0.000 claims abstract description 13
- 235000019640 taste Nutrition 0.000 claims abstract description 12
- 229940079593 drug Drugs 0.000 claims abstract description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 59
- 238000000605 extraction Methods 0.000 claims description 58
- 244000116484 Inula helenium Species 0.000 claims description 50
- 235000002598 Inula helenium Nutrition 0.000 claims description 50
- 244000062241 Kaempferia galanga Species 0.000 claims description 50
- 235000013421 Kaempferia galanga Nutrition 0.000 claims description 50
- 239000000341 volatile oil Substances 0.000 claims description 38
- 235000019441 ethanol Nutrition 0.000 claims description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- 238000002156 mixing Methods 0.000 claims description 21
- 239000000243 solution Substances 0.000 claims description 21
- 239000000463 material Substances 0.000 claims description 16
- 239000007864 aqueous solution Substances 0.000 claims description 14
- 238000000926 separation method Methods 0.000 claims description 12
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- 230000001070 adhesive effect Effects 0.000 claims description 10
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- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 8
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- 238000012545 processing Methods 0.000 claims description 7
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- 239000002893 slag Substances 0.000 claims description 6
- 229930006000 Sucrose Natural products 0.000 claims description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 5
- 238000011049 filling Methods 0.000 claims description 5
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 claims description 5
- 238000004064 recycling Methods 0.000 claims description 5
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- 238000001694 spray drying Methods 0.000 claims description 4
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- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 3
- 235000010234 sodium benzoate Nutrition 0.000 claims description 3
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- 238000000034 method Methods 0.000 abstract description 33
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- 238000001035 drying Methods 0.000 abstract description 9
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- 239000007909 solid dosage form Substances 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000012360 testing method Methods 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 9
- 238000004090 dissolution Methods 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 239000007921 spray Substances 0.000 description 9
- XVPBINOPNYFXID-JARXUMMXSA-N 85u4c366qs Chemical compound C([C@@H]1CCC[N@+]2(CCC[C@H]3[C@@H]21)[O-])N1[C@@H]3CCCC1=O XVPBINOPNYFXID-JARXUMMXSA-N 0.000 description 8
- 229930015582 oxymatrine Natural products 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
- 239000006071 cream Substances 0.000 description 7
- 238000013461 design Methods 0.000 description 7
- 230000004584 weight gain Effects 0.000 description 7
- 235000019786 weight gain Nutrition 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- ZSBXGIUJOOQZMP-UHFFFAOYSA-N Isomatrine Natural products C1CCC2CN3C(=O)CCCC3C3C2N1CCC3 ZSBXGIUJOOQZMP-UHFFFAOYSA-N 0.000 description 6
- ZSBXGIUJOOQZMP-JLNYLFASSA-N Matrine Chemical compound C1CC[C@H]2CN3C(=O)CCC[C@@H]3[C@@H]3[C@H]2N1CCC3 ZSBXGIUJOOQZMP-JLNYLFASSA-N 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 229930014456 matrine Natural products 0.000 description 6
- 238000005453 pelletization Methods 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 6
- 239000011122 softwood Substances 0.000 description 6
- 235000019658 bitter taste Nutrition 0.000 description 5
- 238000007689 inspection Methods 0.000 description 5
- 238000011068 loading method Methods 0.000 description 5
- 239000013558 reference substance Substances 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- PXOYOCNNSUAQNS-AGNJHWRGSA-N alantolactone Chemical compound C1[C@H]2OC(=O)C(=C)[C@H]2C=C2[C@@H](C)CCC[C@@]21C PXOYOCNNSUAQNS-AGNJHWRGSA-N 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 235000013312 flour Nutrition 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 241000395033 Kaempferia Species 0.000 description 3
- 235000013422 Kaempferia rotunda Nutrition 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- CVUANYCQTOGILD-QVHKTLOISA-N isoalantolactone Chemical compound C1CCC(=C)[C@@H]2C[C@@H]3C(=C)C(=O)O[C@@H]3C[C@]21C CVUANYCQTOGILD-QVHKTLOISA-N 0.000 description 3
- CVUANYCQTOGILD-UHFFFAOYSA-N isoalantolactone Natural products C1CCC(=C)C2CC3C(=C)C(=O)OC3CC21C CVUANYCQTOGILD-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- PXOYOCNNSUAQNS-UHFFFAOYSA-N alantolactone Natural products C1C2OC(=O)C(=C)C2C=C2C(C)CCCC21C PXOYOCNNSUAQNS-UHFFFAOYSA-N 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000007493 shaping process Methods 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- UHZZMRAGKVHANO-UHFFFAOYSA-M chlormequat chloride Chemical compound [Cl-].C[N+](C)(C)CCCl UHZZMRAGKVHANO-UHFFFAOYSA-M 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- QMGGMESMCJCABO-UHFFFAOYSA-N n-oxysophocarpine Chemical compound C12C3CCC[N+]2([O-])CCCC1CN1C3CC=CC1=O QMGGMESMCJCABO-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000014860 sensory perception of taste Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 235000020985 whole grains Nutrition 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger 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)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- 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)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/37—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)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses the preparation methods that a kind of anaesthetic looks into dry soup pellet and soup mixture, look into dry soup pellet with technique be respectively beta cyclodextrin clathrate process, drying process with atomizing, art for coating, while active ingredient is sufficiently reserved, improve poor taste, it is inconvenient to carry, take the problems such as inconvenient；The instructions of taking that dry soup mixture is sufficiently reserved former dosage form powder is looked into, based on traditional Chinese herbal decoction, extracts active ingredient in drug, preparation process is easy, is easy to technology production；This dosage form compensates for the deficiency of solid dosage forms, improves bioavilability, its main feature is that taking dose is small, it is fast to absorb, it is rapid to prove effective, is easily received by patient.
Description
Technical field
The present invention relates to pharmaceutical formulating arts, and in particular to a kind of anaesthetic looks into the preparation method of dry soup pellet and soup mixture.
Background technology
Presently commercially available Sophara Flavescens Ait is to be ground into coarse powder by elecampane, kuh-seng, Ramulus Rubi, kaempferia galanga four traditional Chinese medicine material,
Sieving, mixing are prepared；Instructions of taking is is decocted in water for oral dose；It is raw in kuh-seng during decoction due to containing kuh-seng in Sophara Flavescens Ait
Alkaloids constituents can stimulate the sense of taste, make Sophara Flavescens Ait mouthfeel extremely bitter, be not easy to take, particularly with children.
Invention content
To solve the above problems, the present invention provides the preparation methods that a kind of anaesthetic looks into dry soup pellet and soup mixture.
To achieve the above object, the technical solution taken of the present invention is：
A kind of anaesthetic looks into the preparation method of dry soup pellet, includes the following steps：
S1, it weighs after appropriate elecampane, kaempferia galanga, kuh-seng and Ramulus Rubi crush respectively, it is thick to obtain elecampane coarse powder, kaempferia galanga
Powder, kuh-seng coarse powder and Ramulus Rubi coarse powder；
S2, supercritical CO is carried out to the elecampane coarse powder of gained, kaempferia galanga coarse powder respectively2Extraction processing obtains elecampane volatilization
Oil, kaempferia galanga volatile oil, the elecampane dregs of a decoction and the kaempferia galanga dregs of a decoction；
S3, the elecampane dregs of a decoction of gained, the dregs of a decoction of kaempferia galanga, kuh-seng coarse powder, Ramulus Rubi coarse powder are compared into building by its quality
Incense drug slag: kuh-seng coarse powder: Ramulus Rubi coarse powder: the kaempferia galanga dregs of a decoction=4: after 4: 2: 1 ratio mixing, 9 times of amount water water is added to carry three
Secondary, each 0.5h, filtering obtains aqueous solution；
S4, by S3 water carry three times gained aqueous solution merge after be concentrated into 1300mL, while hot under the conditions of 3500rpm/min
10min is centrifuged, supernatant is taken to be spray-dried, obtains powder；
S5, by the elecampane volatile oil of gained, kaempferia galanga volatile oil mix after, using after beta-cyclodextrin inclusion compound with S4 obtained by
After powder mixing, after addition appropriate amount of auxiliary materials stirs evenly, pellet is made by extrusion spheronization machine；
S6, pellet obtained is subjected to film coating to get coating micro-pill.
Preferably, the appropriate amount of auxiliary materials in the step S5 be adhesive, the adhesive be 20% ethanol solution, medicinal powder:
The ratio mixing gained of microcrystalline cellulose in mass ratio 1: 1.25.Preferably, beta-cyclodextrin and volatile oil in the step S5
Mass ratio is 4: 0.5 (8: 1), includes temperature 50 C, and the inclusion time is 2 hours.
Preferably, the parameter of the spray drying is：140 DEG C of intake air temperature, 0.7 (M of hot air flow3/ h), charging speed
It spends (600mL/h), dry powder yield 82.23%, moisture 4.2%.
Preferably, the supercritical CO2The response parameter of extraction is：Extracting pressure is 20MPa, 35 DEG C of temperature, detaches I
40 DEG C of pressure 9MPa, temperature, separation II pressure 5MPa, 35 DEG C of temperature, carry out cycling extraction；CO2Flow is 150L/h, extraction 3
After hour, extract, yield are collected：3.5%.
The present invention provides the preparation methods that a kind of anaesthetic looks into dry soup mixture, include the following steps：
S1, it weighs after appropriate elecampane, kaempferia galanga, kuh-seng and Ramulus Rubi crush respectively, it is thick to obtain elecampane coarse powder, kaempferia galanga
Powder, kuh-seng coarse powder and Ramulus Rubi coarse powder；
S2, supercritical CO is carried out to the elecampane coarse powder of gained, kaempferia galanga coarse powder respectively2Extraction processing obtains elecampane volatilization
Oil, kaempferia galanga volatile oil, the elecampane dregs of a decoction and the kaempferia galanga dregs of a decoction；The supercritical CO2The response parameter of extraction is：Extracting pressure
For 35 DEG C of 20MPa, temperature, separation I pressure 9MPa, 40 DEG C of temperature, separation II pressure 5MPa, 35 DEG C of temperature carry out cycle extraction
It takes；CO2Flow is 150L/h, after extracting 3 hours, collects extract, yield：3.5%.
S3, the elecampane dregs of a decoction of gained, the dregs of a decoction of kaempferia galanga, kuh-seng coarse powder, Ramulus Rubi coarse powder are compared into building by its quality
Incense drug slag: kuh-seng coarse powder: Ramulus Rubi coarse powder: the kaempferia galanga dregs of a decoction=4: after 4: 2: 1 ratio mixing, 9 times of amount water water is added to carry three
Secondary, each 0.5h, filtering obtains aqueous solution；
S4, S3 water is carried gained three times aqueous solution merge after be concentrated into 500mL, add in absolute ethyl alcohol, alcohol content be made
It for 60% solution, stands for 24 hours, centrifuges 10min under the conditions of 3500rpm/min while hot, take supernatant, recycling ethyl alcohol to nothing
Alcohol taste, and it is 1.3 to be concentrated into relative density, adds white sugar, volatile oil, appropriate sodium benzoate, is adjusted to full dose with purified water, fully
It stirs evenly, filling, sterilizing, thus obtaining the product.
The invention has the advantages that：
Using drying process with atomizing, drying process is very fast, malleable drying condition, adjusts target level of product quality, can
To change operating condition in wide range to control the quality index of product, such as size distribution, moisture content, bioactivity, molten
Xie Xing, color etc.；Can convection drying into powder；Production efficiency is high, and operating personnel are few；Production capacity is big, product quality
It is high；By the combination of beta-cyclodextrin inclusion compound technique, extrusion spheronization technique, art for coating, it is being sufficiently reserved the same of active ingredient
When, the stability of volatile ingredient and oxidizable ingredient is increased, while solve former dosage form poor taste, carry and take not
The problems such as convenient.
The preparation method that the anaesthetic of the present invention looks into dry soup mixture remains traditional instructions of taking, greatly remains
Effective component promotes the stripping quantity and dissolution rate of substance in vivo in crude drug cell, improves drug effect；And technological process is easy
Feasible, convenient for children and different age people are taken.
Specific embodiment
In order to which objects and advantages of the present invention are more clearly understood, the present invention is carried out with reference to embodiments further
It is described in detail；It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to limit this hair
It is bright.
Embodiment 1
A kind of anaesthetic looks into the preparation method of dry soup pellet, includes the following steps：
S1, it weighs after appropriate elecampane, kaempferia galanga, kuh-seng and Ramulus Rubi crush respectively, it is thick to obtain elecampane coarse powder, kaempferia galanga
Powder, kuh-seng coarse powder and Ramulus Rubi coarse powder；
S2, supercritical CO is carried out to the elecampane coarse powder of gained, kaempferia galanga coarse powder respectively2Extraction processing obtains elecampane volatilization
Oil, kaempferia galanga volatile oil, the elecampane dregs of a decoction and the kaempferia galanga dregs of a decoction；
S3, the elecampane dregs of a decoction of gained, the dregs of a decoction of kaempferia galanga, kuh-seng coarse powder, Ramulus Rubi coarse powder are compared into building by its quality
Incense drug slag: kuh-seng coarse powder: Ramulus Rubi coarse powder: the kaempferia galanga dregs of a decoction=4: after 4: 2: 1 ratio mixing, 9 times of amount water water is added to carry three
Secondary, each 0.5h, filtering obtains aqueous solution；
S4, by S3 water carry three times gained aqueous solution merge after be concentrated into 1300mL, while hot under the conditions of 3500rpm/min
10min is centrifuged, supernatant is taken to be spray-dried, obtains powder；
S5, by the elecampane volatile oil of gained, kaempferia galanga volatile oil mix after, using after beta-cyclodextrin inclusion compound with S4 obtained by
After powder mixing, after addition appropriate amount of auxiliary materials stirs evenly, pellet is made by extrusion spheronization machine；
S6, pellet obtained is subjected to film coating to get coating micro-pill.
Appropriate amount of auxiliary materials in the step S5 is adhesive, ethanol solution, the medicinal powder which is 20%: microcrystalline cellulose
Obtained by the ratio mixing of element in mass ratio 1: 1.25, the mass ratio of beta-cyclodextrin and volatile oil is 4: 0.5 (8 in the step S5
: 1), temperature 50 C is included, the inclusion time is 2 hours, and the parameter of the spray drying is：140 DEG C of intake air temperature, hot air flow
Measure 0.7 (M3/ h), charging rate (600mL/h), dry powder yield 82.23%, moisture 4.2%, the supercritical CO2Extraction
The response parameter of method is：Extracting pressure is 20MPa, 35 DEG C of temperature, and separation I pressure 9MPa, 40 DEG C of temperature detach II pressure
35 DEG C of 5MPa, temperature carry out cycling extraction；CO2Flow is 150L/h, after extracting 3 hours, collects extract, yield：
3.5%.
Supercritical CO_2 extraction method extracts volatile oil technique
Understand that influence of each factor to oil yield of volatilizing is as follows through experiment of single factor：As 15~35MPa of extracting pressure, receive
Rate increases with pressure rise, and when reaching 25MPa, yield almost reaches maximum value；When extraction temperature is 30~40 DEG C, yield
It is on a declining curve；40~60 DEG C of yields are in rising trend；2h yields increase notable before extraction, almost no longer increase after 2.5h.
The influence two-stage parsing of resolution temperature；Fixed I grades of resolution temperatures are 40 DEG C or so, then II grades of resolution temperature variations pair
Total extract yield influences less, only to influence the amount and content of extracts at different levels；II stage pressures are fixed in the influence of parsing pressure
5MPa or so, then I grades parsing pressure variations influences be same as above；This experiment is due to only total volatile oil to be separated, and purity requirement is not
It is high；Preferable condition is：I grades of parsing pressure and temperatures are 9MPa and 40 DEG C；II grades of parsing pressure and temperatures are 5MPa and 35 DEG C；
CO2Flow influences elecampane, kaempferia galamga volatilization oil yield little.
Orthogonal experiment is carried out on the basis of experiment of single factor, with reference to experiment of single factor as a result, using volatile oil extraction yield as
Inspection target chooses extracting pressure (A), extraction temperature (B), extraction time (C), CO24 factors of flow (D) for investigate because
Element, each 3 levels of factor design carry out the experiment of four factors, three horizontal quadrature.
Table 1 extracts volatile oil orthogonal design table
Using oil yield of volatilizing as evaluation index, 2, table 3 the results are shown in Table；
2 orthogonal experiments of table and data are intuitively analyzed
3 orthogonal experiments of table and data variance analysis
The extracting pressure (A) knowable to above-mentioned each table has a significant impact the extraction of volatile oil, extraction time (C), extraction temperature
Spend (B), CO2Flow (D) takes second place；Supercritical CO2Extraction extracts elecampane, the extracting method of kaempferia galamga volatile oil is extracting pressure
For 35 DEG C of 20MPa, temperature, separation I pressure 9MPa, 40 DEG C of temperature, separation II pressure 5MPa, 35 DEG C of temperature carry out cycle extraction
It takes；CO2Flow is 150L/h, after extracting 3 hours, collects extract, yield：3.5%.
Sophara Flavescens Ait extraction process by water it is preferred
On the basis of trial test and consulting literatures, solvent dosage (again), extraction time (h), extraction time (secondary) are chosen
To investigate factor, each factor sets 3 levels, using the total content of matrine and oxymatrine, dry cream weight as index, takes gained
Elecampane, the dregs of a decoction of kaempferia galanga and kuh-seng, the common 70g of Ramulus Rubi coarse powder, mix (elecampane: kuh-seng: stirrup by its mass ratio
Sub- wood: kaempferia galanga=4: 4: 2: 1) it is, accurately weighed, parallel 9 parts, by L9(33) factor level orthogonal arrage table 4 arrange experiment carried
It takes.
The extraction process orthogonal design table of 4 Sophara Flavescens Ait of table
Using the total content of matrine and oxymatrine, dry cream weight as index, assay is carried out by HPLC methods；Respectively
Following 9 parts of extracting solution 20mL are measured, is put into evaporating dish and is evaporated to constant weight, calculate dry cream dose rate；It the results are shown in Table 5.
5 Sophara Flavescens Ait extracting method analysis of experimental data of table
The optimum extraction process of Sophara Flavescens Ait is A as seen from the above table3B1C3Group, i.e., the medicinal material that four tastes mix in proportion
70g adds the water of 9 times of amounts, extracts 0.5h, extraction is three times.
The clathrate process of beta-cyclodextrin it is preferred
The principal element for influencing inclusion essential oil is the ratio of beta-cyclodextrin and volatile oil, inclusion temperature, mixing time, respectively
Factor takes a level respectively, carries out orthogonal test as index using inclusion compound yield and inclusion rate, screens optimum process condition；Packet
The factor level for closing technique is shown in Table, and the factor level of clathrate process is shown in Table 6 and table 7.
The clathrate process orthogonal test of 6 beta-cyclodextrin of table
The intuitive analytical table of 7 orthogonal test of table
By the analysis on orthogonal experiments it is found that each factor is on the primary and secondary sequence that inclusion compound yield influences：B is included
The ratio ＞ C mixings time of temperature ＞ A beta-cyclodextrins and volatile oil, and obtain optimum extraction process：A2B2C3, i.e. temperature 50
DEG C, the ratio of beta-cyclodextrin and volatile oil is 8: 1, mixing time 2 hours.
Drying process with atomizing is preferred
On the basis of trial test and consulting literatures, choose intake air temperature, hot air flow, charging rate for investigate because
Element, each factor set 3 levels, using spray powder powder outlet quantity, spray powder water content as index, by L9(33) orthogonal arrage arrangement examination
It tests, takes extracting solution, be divided into 9 parts, be spray-dried, factor level is shown in Table 8.
8 drying process with atomizing orthogonal design table of table
Version in 2015 is pressed as index determinations of moisture using the water content of spray powder powder outlet quantity, spray powder《Chinese Pharmacopoeia》4th
The first method measures under portion's aquametry item；
Flour extraction (%)=spray dried powder weight (g)/dry cream weight (g) × 100%.
It the results are shown in Table 9
9 moisture of table, the intuitive analytical table of flour extraction
Variance analysis
Variance analysis is carried out to flour extraction and moisture respectively, it is suitable to influence size on powder outlet quantity for each factor as shown in Table 10
Sequence is A ＞ C ＞ B, i.e. A intake air temperatures have a significant impact to powder outlet quantity；As shown in Table 11 influence of each factor to moisture according to
Secondary is B ＞ A ＞ C, i.e. B hot air flows have a significant impact to moisture；In combination with the face shaping overall merit of powder
Selection process is A3B3C2；That is 140 DEG C of intake air temperature, hot air flow are 0.70 (M3/ h), charging rate 600mL/h.
10 flour extraction analysis of variance table of table
11 moisture analysis of variance table of table
Preparations shaping technical study
Prepare pellet (using extrusion spheronization method)
Medicinal powder with auxiliary material by proper ratio is mixed, after softwood is made, is put into extrusion spheronization granulator, wind turbine is adjusted and becomes
Frequently within certain round as a ball time, pellet is made in, ball blast frequency conversion size；The arrange parameter of extrusion spheronization machine is shown in Table 12.
The arrange parameter of 12 extrusion spheronization machine of table
According to trial test it is found that fan frequency conversion range is in 5-10Hz, between 20-30Hz, pelletization performance is endured for ball blast frequency conversion
It is good；And fan frequency conversion range is in 10-20Hz, for ball blast variable frequency range between 40-50Hz, pelletization performance is not pelletization；So
Fan frequency conversion is respectively selected as 10Hz and 20Hz with ball blast frequency conversion.
The auxiliary material of pellet is preferred
The investigation of categories of excipients
Microcrystalline cellulose (MCC) is common pellet excipient, can retain moisture, when preparing softwood, be can control in wet feed
The movement and distribution of water reduce stickiness；During pelletization, the plasticity of material can be increased, cylinder is made to be easy to round as a ball, had certain
Adhesive effect assigns pellet certain intensity, is a kind of excellent balling-up accelerating agent；
Since this prescription drug viscosity itself is larger, therefore consider to be added without the bondings such as starch, it is pre- that pellet is coated, therefore
Consideration, which does not add the flavoring agents such as sucrose, improves mouthfeel.So directly mixed in proportion with MCC with medicinal powder, using pelletization performance as
Index is screened；It the results are shown in Table 13；
The investigation of 13 categories of excipients of table
As shown in Table 13, on the basis of preliminary experiment, the ratio of fixed powder and MCC is 1: 1.25, fan frequency conversion 10Hz,
Ball blast frequency conversion 20Hz；Pelletization performance and appearance character are best
The selection of adhesive
On the basis of preliminary experiment, fixed excipients microcrystalline cellulose: medicinal powder in mass ratio 1: 1.25 is separately added into appropriate
Water, 5% ethyl alcohol, 10% ethyl alcohol, 20% ethyl alcohol, 30% ethyl alcohol, 40% ethyl alcohol adhesive softwood the results are shown in Table 14；
The selection of 14 adhesive of table
As shown in Table 14：When adhesive is 20% ethyl alcohol, qualified softwood can be made.
By above-mentioned each table it is found that best moulding process be by the ratio of medicinal powder and auxiliary material be 1: 1.25, be uniformly mixed, it is auxiliary
Expect for MCC, then it is adhesive to spray 20% ethyl alcohol；Softwood processed is put into extruder, and adjusting fan frequency conversion is 10Hz, and ball blast becomes
Frequently it is 20Hz, in 3min, pellet is made in softwood；
The film coating procedure of pellet
Extremely bitter due to looking into the prescription medicinal material kuh-seng taste in dry soup, the micropill preparation being prepared into cannot cover its bitter taste, therefore adopt
Film coating is taken to cover its bitter taste, the inclusion compound of beta-cyclodextrin inclusion compound volatile oil is mixed to system packet with spray dried powder
Clothing pellet, this product look into dry soup coating of pellets, mask the bitter taste of drug, obtain satisfactory effect；
Coating solution is prepared：
Accurately weigh film coating pre-mix dose (stomach dissolution type) Opadry Chinese medicine coating powder, in terms of 5% weightening, 300g pellets
Need of coating powder：300 × 5%=15g, solid-to-liquid ratio 15%, the then amount for needing addition distilled water are：15/0.15=100mL；
Distilled water is added in suitable container, starts blender, entire liquid level forms whirlpool, drives the liquid in whole container, but
Mixing speed should not be too fast, in order to avoid it is involved in excessive air；Coating powder is at the uniform velocity added in whirlpool, powder floats should not be made to exist
On liquid level, charging process should complete charging in 5 min and finish, and adjust mixing speed, and entire solution is made to maintain rotation 45min,
Complete blending process；
Coating operations：
Pellet taking-up is put in drier and cooled, whole grain is sieved with 16 mesh and 32 mesh, taking can cannot be by 32 mesh by 16 mesh
The pellet of sieve is qualified pellet；Pellet is put into mixing in Mixers with Multi-direction Movement before coating, to ensure the uniformity of sample；Choosing
With bottom spray type fluidized bed coating equipment, by result of the test it can be seen that：Atomizing pressure, intake air temperature and transfusion speed are to preparation
Quality also has important influence；Pressure is bigger, and the spray droplet of coating solution is smaller, and the clothing film formed is more uniform；Temperature is too
Height be easy to cause the spray drying of coating solution, it is impossible to form the clothing film of continuous uniform；Transfusion speed is too fast, then due to drying not
Abundant and easy adhesion influences the formation quality of clothing film, reduces coating efficiency and finished product yield；
Therefore it is last we select air blast frequency be 30Hz, atomizing pressure 0.12MPa, coating flow velocity be 5.0~
50 DEG C of 10r/min, inlet air temperature, temperature of charge are controlled under the conditions of 40 DEG C, and the film coating using the happy Kanggong department production of card is pre-
Mixture (stomach dissolution type) Opadry Chinese medicine aqueous dispersion is coated for coating material；
It with the increase of coating weight gain, improves significantly to the cover of bitter taste, but because coating material is that influence coating is micro-
One of main factor of ball release characteristics, therefore the influence to coating weight gain is investigated, it is respectively 5% to take coating weight gain,
10% and uncoated pellet, investigate influence of the coating weight gain to drug release；It the results are shown in Table 15,16；
15 coating micro-pill mouthfeel of table, color and luster compare
Table 16 is coated front and rear pellet dissolution rate and compares
From table 15,16：The effect that the pellet of coating weight gain 10% covers bitter taste is best, and uncoated pellet and packet
The dissolution rate difference of clothing pellet is little, therefore the pellet of coating weight gain 10% is selected to be coated；
Moisture-resistant test
It is respectively 5%, 10% pellet by uncoated and coating weight gain, is exposed in air with interior is put, according to conventional survey
Determine pellet change of moisture content, the results are shown in Table 17；
As can be seen from the table, with the variation of exposure duration in air, coating micro-pill moisture content change is little, but does not have
Significant changes occur for the moisture of coating micro-pill, hence it is evident that increase；
The variation (%) of water content after being placed whether 17 coating of pellets of table
Embodiment 2
A kind of anaesthetic looks into the preparation method of dry soup mixture, includes the following steps：
S1, it weighs after appropriate elecampane, kaempferia galanga, kuh-seng and Ramulus Rubi crush respectively, it is thick to obtain elecampane coarse powder, kaempferia galanga
Powder, kuh-seng coarse powder and Ramulus Rubi coarse powder；
S2, supercritical CO is carried out to the elecampane coarse powder of gained, kaempferia galanga coarse powder respectively2Extraction processing obtains elecampane volatilization
Oil, kaempferia galanga volatile oil, the elecampane dregs of a decoction and the kaempferia galanga dregs of a decoction；The supercritical CO2The response parameter of extraction is：Extracting pressure
For 35 DEG C of 20MPa, temperature, separation I pressure 9MPa, 40 DEG C of temperature, separation II pressure 5MPa, 35 DEG C of temperature carry out cycle extraction
It takes；CO2Flow is 150L/h, after extracting 3 hours, collects extract, yield：3.5%.
S3, the elecampane dregs of a decoction of gained, the dregs of a decoction of kaempferia galanga, kuh-seng coarse powder, Ramulus Rubi coarse powder are compared into building by its quality
Incense drug slag: kuh-seng coarse powder: Ramulus Rubi coarse powder: the kaempferia galanga dregs of a decoction=4: after 4: 2: 1 ratio mixing, add 9 times of amount water, water carries three
Secondary, each 0.5h, filtering obtains aqueous solution；
S4, S3 water is carried gained three times aqueous solution merge after be concentrated into 500mL, add in absolute ethyl alcohol, alcohol content be made
It for 60% solution, stands for 24 hours, centrifuges 10min under the conditions of 3500rpm/min while hot, take supernatant, recycling ethyl alcohol to nothing
Alcohol taste, and it is 1.3 to be concentrated into relative density, adds white sugar, volatile oil, appropriate sodium benzoate, is adjusted to full dose with purified water, fully
It stirs evenly, filling, sterilizing, thus obtaining the product.
Supercritical CO_2 extraction method extracts volatile oil technique
Orthogonal experiment is carried out on the basis of the experiment of single factor described in embodiment, with reference to experiment of single factor as a result, to wave
Hair oil extraction yield is inspection target, choose extracting pressure (A), extraction temperature (B), extraction time (C), CO2 flows (D) 4 because
Element is investigation factor, and each 3 levels of factor design carry out the experiment of four factors, three horizontal quadrature；Factor level table is shown in Table 18.
Table 18 extracts volatile oil orthogonal design table
Using oil yield of volatilizing as evaluation index, 19, table 20 the results are shown in Table.
19 orthogonal experiments of table and data are intuitively analyzed
20 orthogonal experiments of table and data variance analysis
The extracting pressure (A) knowable to above-mentioned each table has a significant impact the extraction of volatile oil, extraction time (C), extraction temperature
Spend (B), CO2Flow (D) takes second place；Supercritical CO2Extraction extracts elecampane, the extracting method of kaempferia galamga volatile oil is extracting pressure
For 35 DEG C of 20MPa, temperature, separation I pressure 9MPa, 40 DEG C of temperature, separation II pressure 5MPa, 35 DEG C of temperature carry out cycle extraction
It takes；CO2Flow is 150L/h, after extracting 3 hours, collects extract, yield：3.5%.
Sophara Flavescens Ait extraction process by water it is preferred
On the basis of trial test and consulting literatures, solvent dosage (again), extraction time (h), extraction time (secondary) are chosen
To investigate factor, each factor sets 3 levels, using the total content of matrine and oxymatrine, dry cream weight as index, takes gained
Elecampane and kaempferia galanga the dregs of a decoction and kuh-seng, the common 70g of Ramulus Rubi, by its mass ratio mixing (elecampane: kuh-seng: Ramulus Rubi
: kaempferia galanga=4: 4: 2: 1) it is, accurately weighed, parallel 9 parts, by L9(33) factor level orthogonal arrage table 21 arrange experiment extract.
The extraction process orthogonal design table of 21 Sophara Flavescens Ait of table
Using the total content of matrine and oxymatrine, dry cream weight as index, assay is carried out by HPLC methods；Respectively
Following 9 parts of extracting solution 20mL are measured, is put into evaporating dish and is evaporated to constant weight, calculate dry cream weight；It the results are shown in Table 22.
22 Sophara Flavescens Ait extracting method analysis of experimental data of table
The optimum extraction process of Sophara Flavescens Ait is A as seen from the above table3B1C3Group, i.e., the medicinal material that four tastes mix in proportion
70g adds the water of 9 times of amounts, extracts 0.5h, extraction is three times.
Alcohol precipitation concentration it is preferred
The aqueous solution extracted three times is merged, is concentrated to 1800mL, is divided into 6 parts, every part of 300mL, it is straight in a copy of it
It connects and draws 20mL, rotate to doing, assay is carried out using HPLC；Another four parts be respectively prepared alcohol content for 40%, 50%,
60%th, 70%, 80% ethanol solution (stirring slow add soon), stands for 24 hours, 10min is centrifuged under the conditions of 3500rpm/min, is taken
Clear liquid, recycling ethyl alcohol to no alcohol taste carry out assay using HPLC, compare not different alcohol precipitation concentrations to active ingredient kuh-seng
The influence of alkali and oxymatrine.
23 water extract-alcohol precipitation methods experiment data analysis of table
The above results show 60% alcohol precipitation concentration best results, and loss late is less, therefore 60% ethyl alcohol is used to carry out alcohol precipitation
Processing.
Look into dry soup mixture
Elecampane, kaempferia galanga coarse powder supercritical CO2Extraction extracts volatile oil, after elecampane, kaempferia galanga extraction volatile oil
The dregs of a decoction with the coarse powder of other two tastes medicines in proportion mix carry out water carry；The aqueous solution extracted three times is merged, is concentrated to
500mL, add in absolute ethyl alcohol, be made alcohol content be 60% solution, stand for 24 hours, while hot under the conditions of 3500rpm/min from
Heart 10min takes supernatant, and recycling ethyl alcohol is to no alcohol taste, and it is 1.3 to be concentrated into relative density, adds white sugar, volatile oil, benzoic acid
Appropriate sodium is adjusted to full dose with purified water, fully stirs evenly, filling, sterilizing, thus obtaining the product.
It is as follows to look into dry soup micropill preparation, the method for quality control of mixture：
Look into the quality examination of dry soup micropill preparation：
Granularity：Using granularity and double sieve measuring methods of determination of particle size distribution, the weighed weight of object of getting it filled puts the dosage form or product
(it is furnished with closely sealed reception container under the sieve of lower floor) in upper strata (aperture is big) medicine sieve under kind of item, keeps horizontality sieving,
Left and right is round-trip, is patted 3 minutes in sieve, takes the pellet and powder that cannot be sieved and can be sieved by small-bore by large aperture, weighed
Weight calculates its proportion (%)；By No. 1 sieve and it cannot can must not exceed 15% by the summation of No. 5 sieves.
Loss on drying：It is dried under reduced pressure in 80 DEG C to constant weight, less loss weight must not be less than 2.0%.
Dissolution rate compares：Dissolution rate is measured using pulpous state paddling process, water 900mL, constant temperature (37 ± 0.5) are added in stripping rotor
DEG C, precision weighs four each 5g of taste elecampane pellet and puts in stripping rotor respectively, rotating speed 100rmin-1, start timing, respectively at 5,
10th, 15,20,30,40,50, respectively sampling is appropriate by 60min, is filtered through 0.45 μm of miillpore filter, supplements isothermal etc. after filtering immediately
Volume of water and filter cake object；Precision measures appropriate subsequent filtrate and is measured by above-mentioned chromatographic condition, compares in different time dissolution fluid
Alantolactone isoalantolactone, matrine, oxymatrine dissolution rate.
Look into the quality examination of dry soup mixture：
Appearance character：Unless otherwise specified, mixture should be clarified；Storage period must not have mouldy, rancid, foreign matter, discoloration,
Gas or other other denaturalization phenomenons are generated, allow have a small amount of fugitive precipitation shaken.
Suitable additives can be added in as needed, unless otherwise specified, when preparation determines prescription, the prescription it is antibacterial
Effect should meet the regulation of inhibitory effect inspection technique (general rule 1211)；The dosage of sorbic acid and benzoic acid must not exceed 0.3%.
Loading amount：The filling mixture of single dose according to following methods inspection, should meet regulation.
Inspection technique：Test sample 5 is taken, content is poured into the amount through markization respectively and is entered in formula weight cylinder, is inspected at room temperature,
Every loading amount must not be more than 1, and must not be less than the 95% of mark loading amount compared with mark loading amount, less than mark loading amount.
Look into the assay of alantolactone in dry soup, isoalantolactone
The preparation of reference substance solution：Take isoalantolactone reference substance appropriate, it is accurately weighed, add methanol that every 1mL is made about
Solution containing 50 μ g to obtain the final product.
The preparation of test solution：Take this product appropriate, it is finely ground, it takes 0.3g accurately weighed, puts in conical flask with cover, precision adds
Enter methanol 25mL, close plug, weighed weight is stood overnight, and is ultrasonically treated 30 minutes, is let cool, weighed weight is supplied with methanol and subtracted
The weight of mistake, shakes up, and filtering takes subsequent filtrate both to obtain.
Chromatographic condition：Diamonsil C18 (4.6 × 250mm, 5 μm) chromatographic column；With -0.04% phosphoric acid solution (50 of acetonitrile
: 50) it is mobile phase；Flow velocity 1.0mL/min；Detection wavelength 210nm；25 DEG C of column temperature；Sample size is 20 μ L.
Look into the assay of the kuh-seng alkaloid in dry soup
The preparation of reference substance solution：Take oxymatrine reference substance, matrine reference substance appropriate, it is accurately weighed, add acetonitrile-
The mixed solution of absolute ethyl alcohol (80: 20) is respectively prepared every 1 milliliter containing about oxymatrine 0.0438mg, N-Oxysophocarpine
The solution of 0.0142mg to obtain the final product.
The preparation of test solution：Spray-dried powders 0.651g is weighed, it is accurately weighed, it puts in conical flask, the examination of enriching ammonia
Liquid 0.5mL, chloroform 20mL, shakes up, and weighs, and after placing half an hour, ultrasonic 40min is let cool, and weight is supplied with chloroform
Amount, filtering take subsequent filtrate 5mL, neutral alumina (100~200 mesh, 5g, internal diameter 1cm) are crossed, successively with chloroform, trichlorine
Methane: each 20mL elutions of methanol (7: 3) merge eluent, are evaporated, dissolved with appropriate absolute ethyl alcohol, constant volume is in 10mL volumetric flasks
In to get.
Chromatographic condition：Ultimte XB-NH2 (250 × 4.6mm, 5 μm) chromatographic column, with acetonitrile: absolute ethyl alcohol: 3% phosphoric acid
Water (80: 10: 10) mobile phase；Flow velocity is 1mLmin-1；Sample size is 20 μ L；Column temperature：25℃；Detection wavelength：220nm.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, without departing from the principle of the present invention, several improvements and modifications can also be made, these improvements and modifications
It should be regarded as protection scope of the present invention.
Claims (7)
1. a kind of anaesthetic looks into the preparation method of dry soup pellet, which is characterized in that includes the following steps：
S1, it weighs after appropriate elecampane, kaempferia galanga, kuh-seng and Ramulus Rubi crush respectively, obtains elecampane coarse powder, kaempferia galanga coarse powder, hardship
Join coarse powder and Ramulus Rubi coarse powder；
S2, supercritical CO is carried out to the elecampane coarse powder of gained, kaempferia galanga coarse powder respectively2Extraction processing obtains elecampane volatile oil, mountain
A kind of apple volatile oil, the elecampane dregs of a decoction and the kaempferia galanga dregs of a decoction；
S3, the elecampane dregs of a decoction of gained, the dregs of a decoction of kaempferia galanga, kuh-seng coarse powder, Ramulus Rubi coarse powder are pressed into its quality than building incense drug
Slag: kuh-seng coarse powder: Ramulus Rubi coarse powder: the kaempferia galanga dregs of a decoction=4: after 4: 2: 1 ratio mixing, 9 times of amount water water is added to carry three times, every time
0.5h, filtering, obtains aqueous solution；
S4, by S3 water carry three times gained aqueous solution merge after be concentrated into 1300mL, centrifuged under the conditions of 3500rpm/min while hot
10min takes supernatant to be spray-dried, and obtains powder；
S5, by the elecampane volatile oil of gained, kaempferia galanga volatile oil mix after, using after beta-cyclodextrin inclusion compound with the powder obtained by S4
After mixing, after addition appropriate amount of auxiliary materials stirs evenly, pellet is made by extrusion spheronization machine；
S6, pellet obtained is subjected to film coating to get coating micro-pill.
2. a kind of anaesthetic according to claim 1 looks into the preparation method of dry soup pellet, which is characterized in that in the step S5
Appropriate amount of auxiliary materials for adhesive, ethanol solution, medicinal powder which is 20%: the ratio of microcrystalline cellulose in mass ratio 1: 1.25
Example mixing gained.
3. a kind of anaesthetic according to claim 1 looks into the preparation method of dry soup pellet, which is characterized in that in the step S5
The mass ratio of beta-cyclodextrin and volatile oil is 4: 0.5 (8: 1), includes temperature 50 C, and the inclusion time is 2 hours.
4. a kind of anaesthetic according to claim 1 looks into the preparation method of dry soup pellet, which is characterized in that the spray drying
Parameter be：140 DEG C of intake air temperature, 0.7 (M of hot air flow3/ h), charging rate (600mL/h), dry powder yield 82.23%,
Moisture 4.2%.
5. a kind of anaesthetic according to claim 1 looks into the preparation method of dry soup pellet, which is characterized in that the supercritical CO2
The response parameter of extraction is：Extracting pressure is 20MPa, 35 DEG C of temperature, and separation I pressure 9MPa, 40 DEG C of temperature detach II pressure
35 DEG C of 5MPa, temperature carry out cycling extraction；CO2Flow is 150L/h, after extracting 3 hours, collects extract, yield：3.5%.
6. a kind of anaesthetic looks into the preparation method of dry soup mixture, which is characterized in that includes the following steps：
S1, it weighs after appropriate elecampane, kaempferia galanga, kuh-seng and Ramulus Rubi crush respectively, obtains elecampane coarse powder, kaempferia galanga coarse powder, hardship
Join coarse powder and Ramulus Rubi coarse powder；
S2, supercritical CO is carried out to the elecampane coarse powder of gained, kaempferia galanga coarse powder respectively2Extraction processing obtains elecampane volatile oil, mountain
A kind of apple volatile oil, the elecampane dregs of a decoction and the kaempferia galanga dregs of a decoction；
S3, the elecampane dregs of a decoction of gained, the dregs of a decoction of kaempferia galanga, kuh-seng coarse powder, Ramulus Rubi coarse powder are pressed into its quality than building incense drug
Slag: kuh-seng coarse powder: Ramulus Rubi coarse powder: the kaempferia galanga dregs of a decoction=4: after 4: 2: 1 ratio mixing, 9 times of amount water water is added to carry three times, every time
0.5h, filtering, obtains aqueous solution；
S4, S3 water is carried gained three times aqueous solution merge after be concentrated into 500mL, add in absolute ethyl alcohol, alcohol content, which is made, is
60% solution stands for 24 hours, centrifuges 10min under the conditions of 3500rpm/min while hot, takes supernatant, recycling ethyl alcohol to no alcohol
Taste, and it is 1.3 to be concentrated into relative density, adds white sugar, volatile oil, appropriate sodium benzoate, is adjusted to full dose with purified water, fully stirs
It is even, filling, sterilizing, thus obtaining the product.
7. a kind of anaesthetic as claimed in claim 6 looks into the preparation method of dry soup mixture, which is characterized in that the supercritical CO2Extraction
The response parameter followed the example of is：Extracting pressure is 20MPa, 35 DEG C of temperature, and separation I pressure 9MPa, 40 DEG C of temperature detach II pressure
35 DEG C of 5MPa, temperature carry out cycling extraction；CO2Flow is 150L/h, after extracting 3 hours, collects extract, yield：3.5%.
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| CN114767827A (en) * | 2022-04-10 | 2022-07-22 | 西安市胸科医院(西安市结核病胸部肿瘤医院) | Medicament for improving central nervous system inflammation |
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| CN111358846A (en) * | 2020-05-14 | 2020-07-03 | 西安市胸科医院 | Medicament for improving central nervous system inflammation |
| CN114767827A (en) * | 2022-04-10 | 2022-07-22 | 西安市胸科医院(西安市结核病胸部肿瘤医院) | Medicament for improving central nervous system inflammation |
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Application publication date: 20180629 |