CN113599363B - Preparation method of Xinmaitong capsules - Google Patents
Preparation method of Xinmaitong capsules Download PDFInfo
- Publication number
- CN113599363B CN113599363B CN202110971897.2A CN202110971897A CN113599363B CN 113599363 B CN113599363 B CN 113599363B CN 202110971897 A CN202110971897 A CN 202110971897A CN 113599363 B CN113599363 B CN 113599363B
- Authority
- CN
- China
- Prior art keywords
- parts
- extract
- weight
- mixing
- region
- 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
- 239000002775 capsule Substances 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 239000008579 xinmaitong Substances 0.000 title claims abstract description 13
- 239000000284 extract Substances 0.000 claims abstract description 79
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 70
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 62
- 239000000843 powder Substances 0.000 claims abstract description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 46
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 35
- 235000012239 silicon dioxide Nutrition 0.000 claims abstract description 32
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 31
- 229920002472 Starch Polymers 0.000 claims abstract description 31
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 31
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 31
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 31
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 31
- 239000008107 starch Substances 0.000 claims abstract description 31
- 235000019698 starch Nutrition 0.000 claims abstract description 31
- 241000219784 Sophora Species 0.000 claims abstract description 27
- 244000131316 Panax pseudoginseng Species 0.000 claims abstract description 19
- 235000003181 Panax pseudoginseng Nutrition 0.000 claims abstract description 19
- 238000010438 heat treatment Methods 0.000 claims abstract description 17
- 239000008213 purified water Substances 0.000 claims abstract description 16
- 241000157352 Uncaria Species 0.000 claims abstract description 12
- 235000001287 Guettarda speciosa Nutrition 0.000 claims abstract description 10
- 238000000605 extraction Methods 0.000 claims abstract description 10
- 241000427159 Achyranthes Species 0.000 claims abstract description 9
- 244000037364 Cinnamomum aromaticum Species 0.000 claims abstract description 8
- 235000014489 Cinnamomum aromaticum Nutrition 0.000 claims abstract description 8
- 244000179560 Prunella vulgaris Species 0.000 claims abstract description 8
- 235000003365 Ilex pubescens Nutrition 0.000 claims abstract description 7
- 241001100932 Ilex pubescens Species 0.000 claims abstract description 7
- 235000011135 Salvia miltiorrhiza Nutrition 0.000 claims abstract description 6
- 235000008113 selfheal Nutrition 0.000 claims abstract description 6
- 244000061520 Angelica archangelica Species 0.000 claims abstract 3
- 241000304195 Salvia miltiorrhiza Species 0.000 claims abstract 3
- 238000002156 mixing Methods 0.000 claims description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 52
- 238000001035 drying Methods 0.000 claims description 50
- 239000000706 filtrate Substances 0.000 claims description 37
- 238000001914 filtration Methods 0.000 claims description 37
- 235000003143 Panax notoginseng Nutrition 0.000 claims description 26
- 241000180649 Panax notoginseng Species 0.000 claims description 26
- 238000010298 pulverizing process Methods 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 239000002245 particle Substances 0.000 claims description 11
- 230000001105 regulatory effect Effects 0.000 claims description 11
- 239000004744 fabric Substances 0.000 claims description 10
- 238000009835 boiling Methods 0.000 claims description 8
- 239000002244 precipitate Substances 0.000 claims description 8
- 239000006228 supernatant Substances 0.000 claims description 8
- 235000008733 Citrus aurantifolia Nutrition 0.000 claims description 7
- 235000011941 Tilia x europaea Nutrition 0.000 claims description 7
- 239000004571 lime Substances 0.000 claims description 7
- 235000013336 milk Nutrition 0.000 claims description 7
- 239000008267 milk Substances 0.000 claims description 7
- 210000004080 milk Anatomy 0.000 claims description 7
- 238000004806 packaging method and process Methods 0.000 claims description 6
- 244000046101 Sophora japonica Species 0.000 claims description 5
- 235000010586 Sophora japonica Nutrition 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 239000002994 raw material Substances 0.000 claims description 3
- 244000215747 Pachyrhizus erosus Species 0.000 claims 1
- 235000001591 Pachyrhizus erosus Nutrition 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 3
- 244000046146 Pueraria lobata Species 0.000 abstract description 2
- 235000010575 Pueraria lobata Nutrition 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 29
- 238000000034 method Methods 0.000 description 26
- 239000008187 granular material Substances 0.000 description 21
- 241000628997 Flos Species 0.000 description 19
- 239000000463 material Substances 0.000 description 17
- 238000011049 filling Methods 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- RXUWDKBZZLIASQ-UHFFFAOYSA-N Puerarin Natural products OCC1OC(Oc2c(O)cc(O)c3C(=O)C(=COc23)c4ccc(O)cc4)C(O)C(O)C1O RXUWDKBZZLIASQ-UHFFFAOYSA-N 0.000 description 9
- HKEAFJYKMMKDOR-VPRICQMDSA-N puerarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 HKEAFJYKMMKDOR-VPRICQMDSA-N 0.000 description 9
- 238000011068 loading method Methods 0.000 description 8
- 241000125175 Angelica Species 0.000 description 7
- 238000005469 granulation Methods 0.000 description 7
- 230000003179 granulation Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 208000024172 Cardiovascular disease Diseases 0.000 description 5
- 239000002250 absorbent Substances 0.000 description 5
- 230000002745 absorbent Effects 0.000 description 5
- 208000026106 cerebrovascular disease Diseases 0.000 description 5
- 230000002526 effect on cardiovascular system Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- JMGZEFIQIZZSBH-UHFFFAOYSA-N Bioquercetin Natural products CC1OC(OCC(O)C2OC(OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5)C(O)C2O)C(O)C(O)C1O JMGZEFIQIZZSBH-UHFFFAOYSA-N 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- IVTMALDHFAHOGL-UHFFFAOYSA-N eriodictyol 7-O-rutinoside Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C=C3C(C(C(O)=C(O3)C=3C=C(O)C(O)=CC=3)=O)=C(O)C=2)O1 IVTMALDHFAHOGL-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- FDRQPMVGJOQVTL-UHFFFAOYSA-N quercetin rutinoside Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 FDRQPMVGJOQVTL-UHFFFAOYSA-N 0.000 description 4
- IKGXIBQEEMLURG-BKUODXTLSA-N rutin Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@@H]1OC[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-BKUODXTLSA-N 0.000 description 4
- ALABRVAAKCSLSC-UHFFFAOYSA-N rutin Natural products CC1OC(OCC2OC(O)C(O)C(O)C2O)C(O)C(O)C1OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5 ALABRVAAKCSLSC-UHFFFAOYSA-N 0.000 description 4
- 235000005493 rutin Nutrition 0.000 description 4
- 229960004555 rutoside Drugs 0.000 description 4
- 210000000582 semen Anatomy 0.000 description 4
- 239000012085 test solution Substances 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 238000005550 wet granulation Methods 0.000 description 4
- 102000003712 Complement factor B Human genes 0.000 description 3
- 108090000056 Complement factor B Proteins 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 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 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000003825 pressing Methods 0.000 description 3
- 244000132619 red sage Species 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 241000382455 Angelica sinensis Species 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 240000007164 Salvia officinalis Species 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 1
- 241000219780 Pueraria Species 0.000 description 1
- 241000731396 Pueraria montana var. thomsonii Species 0.000 description 1
- 235000017276 Salvia Nutrition 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000011362 coarse particle Substances 0.000 description 1
- 235000005272 common selfheal Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 208000031169 hemorrhagic disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000023589 ischemic disease Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000005412 red sage Nutrition 0.000 description 1
- 239000012088 reference solution Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 229940126673 western medicines Drugs 0.000 description 1
Images
Classifications
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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)
- A61K36/21—Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
-
- 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)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- 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
- A61K36/482—Cassia, e.g. golden shower tree
-
- 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
- A61K36/488—Pueraria (kudzu)
-
- 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)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/536—Prunella or Brunella (selfheal)
-
- 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
- A61K36/537—Salvia (sage)
-
- 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)
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (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)
- Medical Informatics (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Inorganic Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a preparation method of a Xinmaitong capsule, which comprises the following steps: 185 parts of angelica, 185 parts of cassia seed, 125 parts of uncaria, 125 parts of achyranthes, 100 parts of salvia miltiorrhiza, 100 parts of kudzu root, 100 parts of sophora flower bud, 100 parts of pubescent holly root, 100 parts of selfheal and 6 parts of pseudo-ginseng, wherein the extractum is obtained by extraction, 550 parts of sophora flower bud extract, 16 parts of pseudo-ginseng fine powder, 5.5 parts of starch, 77.7 parts of microcrystalline cellulose and 12.5 parts of silicon dioxide, the mixture is mixed, a proper amount of purified water is added and uniformly mixed, dried into dry paste by a vacuum belt type (the heating temperature is 110 ℃ in a 1 region, 95 ℃ in a 2 region, 80 ℃ in a 3 region, the crawler speed is 12HZ, the feeding speed is 12 HZ), 80-mesh crushing is carried out, and then the dry paste is mixed with 2.5 parts of magnesium stearate to prepare capsules and then the capsule is packaged.
Description
Technical Field
The invention relates to a preparation method of a Xinmaitong capsule, in particular to a preparation method of a preparation mode. Belongs to the technical field of medicine.
Technical Field
Cardiovascular and cerebrovascular diseases are the general names for cardiovascular and cerebrovascular diseases, and generally refer to ischemic or hemorrhagic diseases of heart, brain and systemic tissues caused by hypertension, hyperlipidemia and the like. According to the statistics of relevant departments, about 50 percent of diabetes patients are combined with various senile diseases such as hypertension, hyperlipidemia and the like. Cardiovascular and cerebrovascular diseases are common diseases seriously threatening the health of human beings, especially the middle-aged and old people over 50 years old, and have high morbidity, high disability rate and high mortality. The number of people dying from cardiovascular and cerebrovascular diseases every year in the world is as high as 1500 thousands of people, and the people live at the first position of various causes of death. Because western medicines have large side effects, the traditional Chinese medicine preparation becomes the first choice for patients in long-term recuperation and long-term treatment.
A Chinese medicine in the form of capsule for treating cardiovascular and cerebrovascular diseases is prepared from 10 Chinese-medicinal materials including Chinese angelica root, cassia seed, uncaria stem with hooks, achyranthes root, red sage root, pueraria root, sophora flower bud, pubescent holly root, prunella spike, notoginseng, etc through preparing capsule.
Has effects of promoting blood circulation for removing blood stasis, dredging collaterals, nourishing heart, lowering blood pressure and reducing blood lipid, and can be used for treating hypertension, hyperlipidemia, etc. Has obvious clinical curative effect and wide application.
The invention provides a method for improving the stability of a medicine by changing a preparation mode.
The Xinmaitong capsule is prepared from the following Chinese medicinal raw materials (by weight). The prescription of the Xinmaitong capsule is as follows:
angelica 185, cassia seed 185, uncaria stem with hooks 125, achyranthes root 125
Radix Salviae Miltiorrhizae 100 radix Puerariae 100 flos Sophorae Immaturus 100 radix Ilicis Pubescentis 100
Prunellae Spica 100 Notoginseng radix 6
[ PREPARATION METHOD ] in the above ten medicinal materials, except that pseudo-ginseng is smashed into fine powder, sophora flower bud is added into boiling water, then the pH value is adjusted to 8.5 by lime milk, and then the materials are decocted twice, filtered, the filtrate is combined, the pH value is adjusted to 4.0-5.0 by hydrochloric acid, the mixture is kept stand for 24 hours, the precipitate is filtered, dried and smashed into fine powder, angelica and uncaria are added with water and decocted twice, filtered, the filtrate is combined, the filtrate is concentrated to a proper amount, ethanol is added to ensure that the ethanol content is 70%, the mixture is kept stand for 24 hours, the supernatant is filtered, the ethanol is recovered from the filtrate, and the filtrate is concentrated to thick paste. Decocting the rest six materials with water twice, filtering, mixing filtrates, and concentrating to obtain soft extract. Mixing the above soft extract with Notoginseng radix fine powder, flos Sophorae Immaturus extract fine powder, starch, microcrystalline cellulose, and 1% magnesium stearate, granulating, drying, and making into 1000 capsules.
The extract prepared by the existing method has large amount and small auxiliary material space, and the capsule prepared by the conventional wet granulation has short shelf life and is very easy to fail in the effective period, thereby influencing the curative effect.
In order to solve the problems and improve the quality of the medicine, the inventor preferably obtains a novel preparation method of the traditional Chinese medicine Xinmaitong capsule through a large number of experiments.
Disclosure of Invention
The invention aims to provide a preparation method of Xinmaitong capsules. The invention improves the stability of the medicine by changing the preparation mode. The invention also provides a vacuum belt type drying technology.
The purpose of the invention is realized by the following steps: the stability of the medicine is improved by continuously optimizing the process of the prescription.
The Xinmaitong capsule is prepared from the following traditional Chinese medicine raw materials in parts by weight:
185 parts of angelica sinensis, 185 parts of semen cassiae, 125 parts of uncaria, 125 parts of achyranthes root
Radix Salviae Miltiorrhizae 100 parts, radix Puerariae 100 parts, flos Sophorae 100 parts, and radix Ilicis Pubescentis 100 parts
Selfheal 100 parts and notoginseng 6 parts
The preparation method comprises the following steps:
1) Crushing: pulverizing Notoginseng radix to obtain Notoginseng radix powder;
2) Extracting the sophora flower buds: decocting flos Sophorae Immaturus in boiling water for 1-3 times, filtering, mixing filtrates, standing, filtering to obtain precipitate, drying, and pulverizing into fine powder;
3) Extracting angelica and uncaria: decocting with 5-10 times of water for 1-3 times, each for 1-3 hr, filtering, concentrating the filtrate, adding ethanol, standing, collecting supernatant, filtering, recovering ethanol from the filtrate, and concentrating to obtain extract;
4) The extraction of the six medicines of the salvia miltiorrhiza, the radix puerariae, the cassia seed, the pubescent holly root, the selfheal and the twotooth achyranthes root: decocting with 5-10 times of water for 1-3 times (each for 1-3 hr), filtering, and concentrating the filtrate to obtain extract;
5) Granulating; mixing the above two extracts with Notoginseng radix powder, flos Sophorae Immaturus extract, starch, microcrystalline cellulose, and absorbent, adding appropriate amount of purified water, mixing, vacuum belt drying to obtain dry extract, pulverizing, and mixing with magnesium stearate.
Wherein the absorbent is selected from: silicon dioxide, aluminum hydroxide, talcum powder, calcium hydrophosphate and mannitol. The amount thereof is 5-20 parts by weight.
Preferably, the preparation method comprises the following steps:
1) Crushing: pulverizing Notoginseng radix to obtain Notoginseng radix powder;
2) Extracting the sophora flower buds: adding sophora flower bud into boiling water, regulating pH to 8-9 with lime milk, decocting for 2 times, filtering, combining filtrates, regulating pH to 4.0-5.0 with hydrochloric acid, standing, filtering to obtain precipitate, drying, and pulverizing into fine powder;
3) Extracting angelica and uncaria: decocting with 6-8 times of water for 2 times, each for 1 hr, filtering, concentrating the filtrate to appropriate amount, adding ethanol to ethanol content of 60-80%, standing, filtering the supernatant, recovering ethanol from the filtrate, and concentrating to obtain extract;
4) The extraction of the six medicines of the salvia miltiorrhiza, the radix puerariae, the cassia seed, the pubescent holly root, the selfheal and the twotooth achyranthes root: adding 7-9 times of water, decocting for 2 times, each time for 1 hr, filtering, and concentrating the filtrate to obtain extract;
5) And (3) granulating: mixing the above two extracts with Notoginseng radix powder, flos Sophorae Immaturus extract, starch, microcrystalline cellulose, and silicon dioxide, adding appropriate amount of purified water, mixing, vacuum belt drying to obtain dry extract, pulverizing, and mixing with magnesium stearate.
Most preferably, the preparation method of the invention comprises the following steps:
1) Crushing: pulverizing Notoginseng radix to obtain fine powder with particle size of 80 meshes.
2) Extracting the sophora japonica: adding sophora flower bud into boiling water, regulating pH to 8.5 with lime milk, decocting twice, filtering, combining filtrates, regulating pH to 4.0-5.0 with hydrochloric acid, standing for 24 hr, filtering to obtain precipitate, drying, pulverizing into fine powder;
3) Extracting angelica and uncaria: decocting with 7 times of water twice, each for 1 hr, filtering with 200 mesh filter cloth, concentrating the filtrate to appropriate amount, adding ethanol to ethanol content of 70%, standing for 24 hr, filtering the supernatant, recovering ethanol from the filtrate, and concentrating the filtrate to 1.20-1.30 to obtain extract;
4) The extraction of the six medicines of the root of red-rooted salvia, the root of kudzu vine, the cassia seed, the pubescent holly root, the common selfheal fruit-spike and the twotooth achyranthes root: decocting with 8 times of water twice, each for 1 hr, filtering with 200 mesh filter cloth, and concentrating the filtrate to 1.20-1.30 to obtain extract;
5) Granulating; mixing the above extract with Notoginseng radix powder, flos Sophorae Immaturus extract, starch, microcrystalline cellulose, and silicon dioxide, adding appropriate amount of purified water, mixing, vacuum belt drying to obtain dry extract (heating temperature 1 region 110 deg.C, 2 region 95 deg.C, 3 region 80 deg.C, track speed 12HZ, feed speed 12 HZ), pulverizing with 80 mesh sieve, and mixing with magnesium stearate to obtain packaged product;
6) Filling; filling with an NJP-3200 model full-automatic capsule filling machine;
7) Pressing a plate; pressing a plate by using a DPT-2000 automatic aluminum-plastic packaging machine;
8) And (6) packaging.
The formula and the preparation method are obtained through a large number of experimental screens.
Prescription design and prescription screening (the following extract is mixed paste of six ingredients such as angelica and uncaria extract and salvia miltiorrhiza)
1. Selection of auxiliary materials (dosage is weight portion)
Fixing: 550 parts of extract, 16 parts of sophora flower bud extract, 5.5 parts of pseudo-ginseng powder, 77.7 parts of starch, 30.5 parts of microcrystalline cellulose and 2.5 parts of magnesium stearate. Respectively taking silicon dioxide, aluminum hydroxide, talcum powder, calcium hydrophosphate and mannitol as absorbents, and granulating and filling according to the preparation methods to obtain a formula I, a formula II, a formula III, a formula IV and a formula V. Making into capsule according to standard prescription. The types of the absorbent are inspected by single factor according to the quality indexes of the capsule such as granulation condition, granule property, loading difference, disintegration time limit, angle of repose and the like, and the prescription design and experimental results are shown in the following table:
from the above test results, the original prescription and the third prescription are difficult to granulate and have a lot of coarse granules; the fifth prescription is difficult to granulate and has more coarse granules; the first prescription, the second prescription and the fourth prescription are feasible for granulation, the granules are better in loading stability, the angle of repose of the granules meets the requirements, but when the silicon dioxide in the first prescription is taken as a glidant, the flowability is best, the disintegration time limit is shortest, and when the silicon dioxide in the second prescription and the silicon dioxide in the fourth prescription are lengthened, the first prescription is selected to be optimal, namely the glidant is the optimal silicon dioxide, in consideration of production benefits.
2. Examination of the amount of silica (amounts in parts by weight)
According to the preferred recipe above, fix: 550 parts of extract, 16 parts of sophora flower bud extract, 5.5 parts of pseudo-ginseng powder, 77.7 parts of starch, 55.5 parts of microcrystalline cellulose and 2.5 parts of magnesium stearate. Respectively taking silicon dioxide 5, 8.75, 12.5, 16.25 and 20 as absorbents, granulating and filling according to the preparation method, carrying out single-factor investigation on the silicon dioxide dosage according to quality indexes such as the granulation condition, the granule property, the loading difference, the disintegration time limit, the angle of repose and the like of capsules, and obtaining the prescription design and the experimental result as shown in the following table:
from the above test results, it can be seen that the first prescription of silicon dioxide is difficult to granulate, the second prescription is difficult to granulate, and the angle of repose is significantly increased, i.e., the flowability is relatively poor, the disintegration time is long, the weight difference deviation is large, and the phenomenon of disqualification exists. When the silicon dioxide dosage reaches more than 12.5, the fluidity is better, the difference of disintegration time limit and loading and the granulation condition is not much different from 16.25 and 20, and when the silicon dioxide dosage is 16.25 and 20, the color of the granules is lighter, so the silicon dioxide dosage of 12.5 is selected as the optimal dosage.
3. Technical introduction of vacuum belt drying:
a vacuum belt type dryer is a contact type vacuum drying device in a continuous feeding and continuous discharging mode, feed liquid to be dried directly enters the dryer in high vacuum through a conveying mechanism, the feed liquid is paved on a plurality of drying belts in the dryer, a motor drives a specially-made rubber roller to drive the drying belts to move along the direction of a cylinder of the dryer at a set speed, three mutually independent heating plates and a cooling plate are arranged below each drying belt, and the drying belts are tightly attached to the heating plates and the cooling plates and transfer energy required by drying to the materials in a contact heat transfer mode. When the drying belt moves to the other end from one end of the cylinder, the materials are dried and cooled, when the drying belt turns back, the dried cakes are peeled off from the drying belt and fall into the crushing device through a cutting device moving up and down, and the crushed materials are discharged through the two air gate type discharging hoppers. Since the material is dried gradually over a period of time (typically 30-60 minutes) directly under high vacuum, the resulting dried particles have a degree of crystallization effect, while having internal micropores as seen from the microstructure. After the particles are directly crushed to the required particle size, the particles have good fluidity, can be directly tabletted or encapsulated, and have good instant solubility because the particles have a microscopic loose structure. Especially for highly viscous, agglomerated, thermoplastic, heat sensitive materials, which are not suitable or feasible for spray drying, vacuum belt dryers are the best choice. And the appearance of the granules is good. Therefore, the technology can effectively increase the product quality and yield, and the equipment utilization rate is high.
The Xinmaitong capsule preparation method is optimized in process and adopts a vacuum belt drying technology. Orthogonal experiments are carried out according to the level of 4 factors and 3 by taking the water content and the puerarin content as evaluation indexes, and the experimental results and the variance analysis are shown in the following table.
Table 1 4-factor 3 level table for vacuum belt drying process orthogonal test
Table 2 vacuum belt drying orthogonal experimental table
TABLE 3 analysis of variance of results of orthogonal tests of vacuum belt drying process
Remarking: f critical value greater than 19 is a significant factor
As can be seen from the above table: the main and secondary sequence of the influence of all factors on the water content of the granules is A > B > C, and the optimal A of the water content of the granules 2 B 2 C 2 . The analysis of variance of the water content shows that: the influence of the factor A and the factor B on the water content is significant, and the factor A is more significant than the factor B. The factor C has no obvious influence; the variance analysis of the puerarin content shows that: the influence of the factor A is significant, and the influence of the factor B, C is not obvious. The optimal vacuum belt type drying condition is determined to be A by combining the comprehensive consideration of energy consumption, product quality and the like 2 B 2 C 2 : the heating temperature is 110 ℃ in the 1 region, 95 ℃ in the 2 region, 80 ℃ in the 3 region, the crawler speed is 12HZ, and the feeding speed is 12HZ.
4. Examination of the number of pulverization meshes (20, 40, 60, 80, 100)
According to the preferred recipe, fix: 550 parts of extract, 16 parts of sophora flower bud extract, 5.5 parts of pseudo-ginseng powder, 50 parts of starch, 70.75 parts of microcrystalline cellulose and 2.5 parts of magnesium stearate. Carrying out vacuum belt drying (according to optimal parameters), crushing dried dry paste powder by 20 meshes, 40 meshes, 60 meshes, 80 meshes and 100 meshes respectively, then granulating and filling according to the preparation method, carrying out single-factor investigation on the crushing mesh number according to quality indexes such as the granulation condition, the particle property, the loading quantity difference, the disintegration time limit, the angle of repose and the like of capsules, and having the following formula design and experimental results:
from the above test results, it is known that the dry paste powder has more coarse particles passing through 20 meshes, 40 meshes and 60 meshes, large angle of repose, poor fluidity and long disintegration time; the powder is too much when the powder is sieved by 100 meshes, and the disintegration time, the loading quantity difference and the angle of repose of the powder all meet the requirements; the granulation is feasible when the particle size is larger than 80 meshes, the granules are better, the loading is stable, the disintegration time and the angle of repose all meet the requirements, and the 80 meshes are comprehensively considered and selected.
Therefore, the optimal process is preferably as follows:
(1) crushing; pulverizing Notoginseng radix to obtain fine powder with particle size of 80 meshes.
(2) Extracting the sophora japonica; adding sophora flower bud into boiling water, regulating pH value to 8.5 with lime milk, decocting twice, filtering, combining filtrates, regulating pH value to 4.0-5.0 with hydrochloric acid, standing for 24 hr, filtering to obtain precipitate, drying, and pulverizing into fine powder.
(3) Extracting radix Angelicae sinensis and ramulus Uncariae cum uncis; adding 7 times of water, decocting twice, each time for 1 hr, filtering with 200 mesh filter cloth, and concentrating the filtrate to appropriate amount. Adding ethanol to make ethanol content 70%, standing for 24 hr, collecting supernatant, filtering, recovering ethanol from filtrate, and concentrating to 1.20-1.30.
(4) Extracting Saviae Miltiorrhizae radix, radix Puerariae, semen Cassiae, radix Ilicis Pubescentis, prunellae Spica, and Achyranthis radix; decocting with 8 times of water twice, each for 1 hr, filtering with 200 mesh filter cloth, and concentrating the filtrate to 1.20-1.30.
(5) Granulating; mixing the above extract with Notoginseng radix powder, flos Sophorae Immaturus extract, starch, microcrystalline cellulose, and silicon dioxide, adding appropriate amount of purified water, mixing, vacuum belt drying to obtain dry extract (heating temperature 1 region 110 deg.C, 2 region 95 deg.C, 3 region 80 deg.C, crawler speed 12HZ, feeding speed 12 HZ), pulverizing with 80 mesh sieve, and mixing with magnesium stearate to obtain packaged product;
(6) filling; filled with an NJP-3200 model fully automatic capsule filling machine.
(7) Pressing a plate; the plate was pressed with a DPT-2000 model automatic aluminum-plastic packaging machine.
(8) Packaging; obtaining the product;
the product inspection results of the optimal prescription and process preparation are as follows:
| inspection item | The result of the detection | Remarks to note |
| Traits | Compliance with regulations | |
| Authentication | Compliance with regulations | |
| Difference in charge | Compliance with regulations | |
| Disintegration time limit | 14 minutes | |
| Moisture content | 2.6％ | |
| Rutin content | 11.2 mg/granule | |
| Puerarin content | 0.36 mg/granule |
[ CONTENT DETERMINATION ] flos Sophorae Immaturus is determined by high performance liquid chromatography (appendix VI D).
Octadecylsilane chemically bonded silica is used as a filling agent in chromatographic condition and system adaptability tests; with acetonitrile-methanol-water-glacial acetic acid (50; the detection wavelength is 254nm. The theoretical plate number is not less than 3000 calculated according to rutin.
Preparation of control solution rutin control 10mg is precisely weighed, placed in a 50ml measuring flask, ultrasonically dissolved by a small amount of methanol, diluted to scale by methanol, shaken up, and then diluted to 10ml by sucking 2ml to obtain (1 ml contains 40 mug rutin).
The preparation of the test solution takes the contents of the product with different filling amounts, evenly mixes, takes 0.1g, precisely weighs, places in a conical flask with a plug, precisely adds 50ml of methanol, weighs, ultrasonically treats for 30 minutes, cools, weighs again, supplements the weight lost by methanol, filters, takes the subsequent filtrate, and filters by a microporous membrane (0.45 mu m) to obtain the test solution.
Pueraria thomsonii is determined by high performance liquid chromatography (appendix VI D of the first part of the 2015 edition of Chinese pharmacopoeia).
Octadecylsilane chemically bonded silica is used as a filler in chromatographic conditions and system applicability experiments; methanol-water (20; the column temperature is 40 ℃, and the detection wavelength is 245nm. The number of theoretical plates is not less than 2000 calculated by puerarin.
Preparation of reference substance solution A proper amount of puerarin reference substance is precisely weighed, and 30% ethanol is added to prepare a solution containing 40 μ g of puerarin per 1 ml.
The preparation method of the test solution comprises mixing the contents of the test solution with different contents, weighing 1g, precisely weighing, placing in a conical flask, precisely adding 50ml of 30% ethanol, weighing, ultrasonically treating for 30 min, cooling, weighing again, supplementing the weight loss with 30% ethanol, shaking, and filtering.
The determination method comprises precisely sucking 10 μ l of each of the reference solution and the sample solution, injecting into liquid chromatograph, and determining.
Compared with the existing method, the preparation method of the invention has the following advantages:
1. the auxiliary materials in the existing prescription of the Xinmaitong capsule are starch, microcrystalline cellulose and magnesium stearate, and considering that the prescription of the product has large paste content and is easy to absorb moisture and agglomerate, the invention adds the auxiliary material silicon dioxide in the prescription, thereby improving the fluidity of the product and improving the stability of the product.
2. The capsule for regulating heart and vein is prepared by wet granulation of extractum and auxiliary materials, and filling of prepared granules, wherein the wet granulation of thick extractum and the filling of the prepared granules are changed into dry extract powder after the total mixing and the direct filling after the dry extract powder is dried by adding the auxiliary materials, because the extraction of the extractum has large amount, the space of the auxiliary materials is small, the conventional wet granulation is difficult, the filling amount is unstable, and the like, so as to solve the problems; the method improves the difficult problem of granulation caused by large extract amount and small auxiliary material space, has unstable filling amount and the like, and improves the production efficiency.
Drawings
FIG. 1 is a flow diagram of vacuum belt drying.
Detailed Description
Examples of the experiments
Extraction (the extraction method is consistent in the following experimental examples):
(1) crushing: 6 parts by weight of pseudo-ginseng is crushed to obtain fine powder with the granularity of 80 meshes.
(2) Extracting the sophora japonica: adding 100 parts by weight of sophora flower bud into boiling water, adjusting the pH value to 8.5 by lime milk, decocting twice, filtering, combining the filtrates, adjusting the pH value to 4.0-5.0 by hydrochloric acid, standing for 24 hours, filtering to obtain a precipitate, drying, and crushing into fine powder.
(3) Extracting 185 parts by weight of angelica and 125 parts by weight of uncaria; adding 7 times of water, decocting twice, each time for 1 hr, filtering with 200 mesh filter cloth, and concentrating the filtrate to appropriate amount. Adding ethanol to make ethanol content 70%, standing for 24 hr, collecting supernatant, filtering, recovering ethanol from filtrate, and concentrating to 1.20-1.30.
(4) Extracting radix Salviae Miltiorrhizae 100 weight parts, radix Puerariae 100 weight parts, semen Cassiae 185 weight parts, radix Ilicis Pubescentis 100 weight parts, spica Prunellae 100 weight parts, and radix Achyranthis bidentatae 125 weight parts; adding 8 times of water, decocting twice, each time for 1 hr, filtering with 200 mesh filter cloth, and concentrating the filtrate to 1.20-1.30.
Experimental example one (prior art): mixing the extract 550, flos Sophorae Immaturus extract 16, notoginseng radix powder 5.5, starch 77.7, and microcrystalline cellulose 55.5, granulating by wet method, drying, and mixing with magnesium stearate 2.5; obtaining a product to be packaged;
experimental example two (prior art): mixing the extract 220, flos Sophorae Immaturus extract 16, notoginseng radix powder 5.5, starch 77.7, and microcrystalline cellulose 55.5, granulating by wet method, drying, and mixing with magnesium stearate 2.5; obtaining a product to be packaged;
experimental example three (inventive process): mixing the extract 550 with 5.5 of pseudo-ginseng powder, 16 of sophora flower bud extract, 77.7 of starch, 30.5 of microcrystalline cellulose and 12.5 of silicon dioxide, adding a proper amount of purified water, uniformly mixing, drying by a vacuum belt type to obtain dry paste (the heating temperature is 110 ℃ in a 1 region, 95 ℃ in a 2 region, 80 ℃ in a 3 region, the crawler speed is 12HZ, the feeding speed is 12 HZ), crushing by 80 meshes, and then mixing with 2.5 of magnesium stearate to obtain a product to be packaged;
experimental example four (inventive process): mixing the extract 550 with pseudo-ginseng powder 5.5, sophora flower bud extract 16, starch 77.7, microcrystalline cellulose 30.5 and silicon dioxide 12.5, adding a proper amount of purified water, uniformly mixing, drying by a vacuum belt type to obtain dry paste (heating temperature is 120 ℃ in 1 region, 105 ℃ in 2 region, 90 ℃ in 3 region, track speed is 16HZ, feeding speed is 16 HZ), crushing by 80 meshes, and mixing with magnesium stearate 2.5 to obtain a product to be packaged;
experimental example five (inventive process): mixing the extract 550 with pseudo-ginseng powder 5.5, sophora flower bud extract 16, starch 77.7, microcrystalline cellulose 30.5 and silicon dioxide 12.5, adding a proper amount of purified water, uniformly mixing, drying by a vacuum belt type to obtain dry paste (the heating temperature is 90 ℃ in a 1 region, 80 ℃ in a 2 region, 70 ℃ in a 3 region, the track speed is 10HZ, the feeding speed is 10 HZ), crushing by 80 meshes, and mixing with magnesium stearate 2.5 to obtain a product to be packaged;
table of test results of experimental examples
Experimental example three accelerated stability test results
The first experimental example is reluctant to form, but the process is not suitable for large-scale production, the differences of properties and loading are unqualified, and the disintegration time limit is obviously increased; in the second experimental example, the identification of the fed extract and the unqualified puerarin content are reduced; the fourth experimental example has longer disintegration time than the third experimental example, and the puerarin content is greatly degraded; the fifth experimental example has longer disintegration time, higher water content and larger degradation of puerarin content than the third experimental example; comprehensive process feasibility and quality detection condition analysis: the third experimental example is the best process; the present invention therefore has unexpected advantages.
The process for determining the final prescription comprises the following steps: mixing the extract 550 with pseudo-ginseng powder 5.5, sophora flower bud extract 16, starch 77.7, microcrystalline cellulose 30.5 and silicon dioxide 12.5, adding a proper amount of purified water, uniformly mixing, drying by a vacuum belt type to obtain dry paste (heating temperature is 110 ℃ in 1 region, 95 ℃ in 2 region, 80 ℃ in 3 region, track speed is 12HZ, feeding speed is 12 HZ), crushing by 80 meshes, mixing with magnesium stearate 2.5, preparing into capsules, and packaging to obtain the following specific embodiment of the invention.
Extraction (the extraction method is consistent in the following examples):
(1) crushing; pulverizing Notoginseng radix 6 to obtain fine powder with particle size of 80 meshes.
(2) Extracting sophora japonica; adding sophora flower bud 100 into boiling water, regulating pH to 8.5 with lime milk, decocting twice, filtering, combining filtrates, regulating pH to 4.0-5.0 with hydrochloric acid, standing for 24 hours, filtering to obtain precipitate, drying, and pulverizing into fine powder.
(3) Extracting radix Angelicae sinensis 185 and ramulus Uncariae cum uncis 125; adding 7 times of water, decocting twice, each time for 1 hr, filtering with 200 mesh filter cloth, and concentrating the filtrate to appropriate amount. Adding ethanol to make ethanol content 70%, standing for 24 hr, collecting supernatant, filtering, recovering ethanol from filtrate, and concentrating to 1.20-1.30.
(4) Extracting Saviae Miltiorrhizae radix 100, radix Puerariae 100, semen Cassiae 185, radix Ilicis Pubescentis 100, prunellae Spica 100, and Achyranthis radix 125; decocting with 8 times of water twice, each for 1 hr, filtering with 200 mesh filter cloth, and concentrating the filtrate to 1.20-1.30.
The first embodiment is as follows: mixing the extract 550, flos Sophorae Immaturus extract 16, notoginseng radix powder 5.5, starch 77.7, microcrystalline cellulose 55.5, and silicon dioxide 25, granulating by wet method to obtain granule, drying, and mixing with magnesium stearate 2.5; obtaining a product to be packaged;
example two: mixing the extract 550, flos Sophorae Immaturus extract 16, notoginseng radix powder 5.5, starch 77.7, microcrystalline cellulose 55.5, and aluminum hydroxide 25, granulating by wet method, drying, and mixing with magnesium stearate 2.5; obtaining a product to be packaged;
example three: mixing the extract 550, flos Sophorae Immaturus extract 16, notoginseng radix powder 5.5, starch 77.7, microcrystalline cellulose 55.5, and pulvis Talci 25, granulating by wet method, drying, and mixing with magnesium stearate 2.5; obtaining a product to be packaged;
example four: mixing the extract 550, flos Sophorae Immaturus extract 16, notoginseng radix powder 5.5, starch 77.7, microcrystalline cellulose 55.5, and calcium hydrogen phosphate 25, granulating by wet method to obtain granule, drying, and mixing with magnesium stearate 2.5; obtaining a product to be packaged;
example five: mixing the extract 550, flos Sophorae Immaturus extract 16, notoginseng radix powder 5.5, starch 77.7, microcrystalline cellulose 55.5, and mannitol 25, granulating by wet method, drying, and mixing with magnesium stearate 2.5; obtaining a product to be packaged;
example six: mixing the extract 550, flos Sophorae Immaturus extract 16, notoginseng radix powder 5.5, starch 77.7, microcrystalline cellulose 55.5, and silicon dioxide 5, granulating by wet method, drying, and mixing with magnesium stearate 2.5; obtaining a product to be packaged;
example seven: mixing extract 550, flos Sophorae Immaturus extract 16, notoginseng radix powder 5.5, starch 77.7, microcrystalline cellulose 55.5, and silicon dioxide 1.25, granulating by wet method, drying, and mixing with magnesium stearate 2.5; obtaining a product to be packaged;
example eight: mixing the extract 550, flos Sophorae Immaturus extract 16, notoginseng radix powder 5.5, starch 77.7, microcrystalline cellulose 55.5, and silicon dioxide 20, granulating by wet method, drying, and mixing with magnesium stearate 2.5; obtaining a product to be packaged;
example nine: mixing the extract 550 with pseudo-ginseng powder 5.5, sophora flower bud extract 16, starch 77.7, microcrystalline cellulose 30.5 and silicon dioxide 12.5, adding a proper amount of purified water, uniformly mixing, drying by a vacuum belt type to obtain dry paste (heating temperature is 110 ℃ in 1 region, 95 ℃ in 2 region, 80 ℃ in 3 region, track speed is 12HZ, feeding speed is 12 HZ), crushing by 80 meshes, and mixing with magnesium stearate 2.5 to obtain a product to be packaged;
example ten: mixing the extract 550 with pseudo-ginseng powder 5.5, sophora flower bud extract 16, starch 77.7, microcrystalline cellulose 30.5 and silicon dioxide 12.5, adding a proper amount of purified water, uniformly mixing, drying by a vacuum belt type to obtain dry paste (heating temperature is 120 ℃ in 1 region, 105 ℃ in 2 region, 90 ℃ in 3 region, track speed is 16HZ, feeding speed is 16 HZ), crushing by 80 meshes, and mixing with magnesium stearate 2.5 to obtain a product to be packaged;
example eleven: mixing the extract 550 with 5.5 of pseudo-ginseng powder, 16 of sophora flower bud extract, 77.7 of starch, 30.5 of microcrystalline cellulose and 12.5 of silicon dioxide, adding a proper amount of purified water, uniformly mixing, drying by a vacuum belt type to obtain dry paste (the heating temperature is 90 ℃ in a 1 region, 80 ℃ in a 2 region, 70 ℃ in a 3 region, the crawler speed is 10HZ, the feeding speed is 10 HZ), crushing by 80 meshes, and then mixing with 2.5 of magnesium stearate to obtain a product to be packaged;
example twelve: mixing the extract 550 with pseudo-ginseng powder 5.5, sophora flower bud extract 16, starch 77.7, microcrystalline cellulose 30.5 and silicon dioxide 12.5, adding a proper amount of purified water, uniformly mixing, drying by a vacuum belt type to obtain dry paste (the heating temperature is 90 ℃ in a 1 region, 80 ℃ in a 2 region, 70 ℃ in a 3 region, the track speed is 10HZ, the feeding speed is 10 HZ), crushing by 40 meshes, and mixing with magnesium stearate 2.5 to obtain a product to be packaged;
example thirteen: mixing the extract 550 with pseudo-ginseng powder 5.5, sophora flower bud extract 16, starch 77.7, microcrystalline cellulose 30.5 and silicon dioxide 12.5, adding a proper amount of purified water, uniformly mixing, drying by a vacuum belt type to obtain dry paste (the heating temperature is 90 ℃ in a 1 region, 80 ℃ in a 2 region, 70 ℃ in a 3 region, the track speed is 10HZ, the feeding speed is 10 HZ), crushing by 60 meshes, and mixing with magnesium stearate 2.5 to obtain a product to be packaged;
example fourteen: mixing the extract 550 with 5.5 of pseudo-ginseng powder, 16 of sophora flower bud extract, 77.7 of starch, 30.5 of microcrystalline cellulose and 12.5 of silicon dioxide, adding a proper amount of purified water, uniformly mixing, drying by a vacuum belt type to obtain dry paste (the heating temperature is 90 ℃ in a 1 region, 80 ℃ in a 2 region, 70 ℃ in a 3 region, the track speed is 10HZ, the feeding speed is 10 HZ), crushing by 100 meshes, and then mixing with 2.5 of magnesium stearate to obtain the product to be packaged.
Claims (1)
1. The preparation method of the Xinmaitong capsule is characterized in that the Xinmaitong capsule is prepared from the following raw material medicines in parts by weight: 185 parts of angelica, 185 parts of cassia seed, 125 parts of uncaria, 125 parts of achyranthes, 100 parts of salvia miltiorrhiza, 100 parts of pachyrhizus angulatus, 100 parts of sophora flower bud, 100 parts of pubescent holly root, 100 parts of selfheal and 6 parts of pseudo-ginseng by weight, and the preparation method comprises the following steps:
1) Crushing: pulverizing Notoginseng radix to obtain fine powder with particle size of 80 mesh;
2) Extracting the sophora japonica: adding sophora flower bud into boiling water, regulating pH to 8.5 with lime milk, decocting twice, filtering, combining filtrates, regulating pH to 4.0-5.0 with hydrochloric acid, standing for 24 hr, filtering to obtain precipitate, drying, and pulverizing into fine powder;
3) Extracting angelica and uncaria: decocting with 7 times of water twice, each for 1 hr, filtering with 200 mesh filter cloth, concentrating the filtrate to appropriate amount, adding ethanol to ethanol content of 70%, standing for 24 hr, filtering the supernatant, recovering ethanol from the filtrate, and concentrating the filtrate to 1.20-1.30 to obtain extract;
4) The extraction of the six medicines of the salvia miltiorrhiza, the radix puerariae, the cassia seed, the pubescent holly root, the selfheal and the twotooth achyranthes root: decocting with 8 times of water twice, each for 1 hr, filtering with 200 mesh filter cloth, and concentrating the filtrate to 1.20-1.30 to obtain extract;
5) Granulating; mixing 550 parts by weight of the extract with 5.5 parts by weight of pseudo-ginseng powder, 16 parts by weight of sophora flower bud extract, 77.7 parts by weight of starch, 30.5 parts by weight of microcrystalline cellulose and 12.5 parts by weight of silicon dioxide, adding a proper amount of purified water, uniformly mixing, drying by a vacuum belt type to form dry paste, heating at the temperature of 110 ℃ in a 1 region, 95 ℃ in a 2 region, 80 ℃ in a 3 region, 12HZ in a crawler speed and 12HZ in a feeding speed, crushing by 80 meshes, mixing with 2.5 parts by weight of magnesium stearate, preparing into capsules, and packaging to obtain the capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110971897.2A CN113599363B (en) | 2021-08-24 | 2021-08-24 | Preparation method of Xinmaitong capsules |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110971897.2A CN113599363B (en) | 2021-08-24 | 2021-08-24 | Preparation method of Xinmaitong capsules |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113599363A CN113599363A (en) | 2021-11-05 |
| CN113599363B true CN113599363B (en) | 2022-11-11 |
Family
ID=78341713
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110971897.2A Active CN113599363B (en) | 2021-08-24 | 2021-08-24 | Preparation method of Xinmaitong capsules |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113599363B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114557966B (en) * | 2022-03-09 | 2023-07-04 | 上海方予健康医药科技有限公司 | Method for producing everolimus solid dispersion through vacuum crawler-type oven |
| CN115487225B (en) * | 2022-09-21 | 2024-02-02 | 江西济民可信药业有限公司 | Preparation method of pagodatree flower bud extract |
| CN115944591A (en) * | 2022-12-22 | 2023-04-11 | 太极集团重庆桐君阁药厂有限公司 | Granulating method of traditional Chinese medicine extract tablet and semi-extract tablet |
| CN116115572A (en) * | 2023-04-19 | 2023-05-16 | 江中药业股份有限公司 | Traditional Chinese medicine composition composite particles and preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1823959A (en) * | 2005-12-12 | 2006-08-30 | 湛江市国基药业有限公司 | Heart vessel free flowing dispersion tablet and its preparation method |
| CN101468087A (en) * | 2007-12-26 | 2009-07-01 | 上海玉森新药开发有限公司 | Method for preparing 'Xinmaitong' granular formulation |
| CN101904948A (en) * | 2010-07-27 | 2010-12-08 | 广东众生药业股份有限公司 | Traditional Chinese medicine preparation of new Zhongsheng pill and preparation method thereof |
| CN104510813A (en) * | 2015-01-10 | 2015-04-15 | 江西济民可信药业有限公司 | Preparation method for Xinmaitong capsules |
-
2021
- 2021-08-24 CN CN202110971897.2A patent/CN113599363B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1823959A (en) * | 2005-12-12 | 2006-08-30 | 湛江市国基药业有限公司 | Heart vessel free flowing dispersion tablet and its preparation method |
| CN101468087A (en) * | 2007-12-26 | 2009-07-01 | 上海玉森新药开发有限公司 | Method for preparing 'Xinmaitong' granular formulation |
| CN101904948A (en) * | 2010-07-27 | 2010-12-08 | 广东众生药业股份有限公司 | Traditional Chinese medicine preparation of new Zhongsheng pill and preparation method thereof |
| CN104510813A (en) * | 2015-01-10 | 2015-04-15 | 江西济民可信药业有限公司 | Preparation method for Xinmaitong capsules |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113599363A (en) | 2021-11-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113599363B (en) | Preparation method of Xinmaitong capsules | |
| CN102423352B (en) | Preparation method of Chinese medicinal granules for treating cardio-cerebrovascular diseases | |
| CN101757073B (en) | Medicinal composition containing atractylodes rhizome extractive | |
| CN101049429A (en) | Tablet for regulating menstruation and removing speckles of department of gynecology, and preparation method | |
| CN104523945A (en) | Chinese veterinary medicine composition for treating yellow-white dysentery of piglets and preparation method and application thereof | |
| CN105726622A (en) | Anti-fatigue traditional Chinese medicine combined extract and its preparation method and use | |
| CN111643594B (en) | Traditional Chinese medicine composition for treating opioid-related constipation, preparation method and application thereof | |
| CN101869644B (en) | Dark-skinned chicken dispersible tablet and preparation process thereof | |
| CN110025652A (en) | It is a kind of to prevent and treat the Herba Abri extract composition of hepatic injury, preparation method and applications | |
| CN105748652B (en) | Serissa japonica capsule for treating gout and preparation method thereof | |
| CN101642480A (en) | Pseudo-ginseng flower leaf oral tablet with function of reducing fever and preparation method thereof | |
| CN101856381A (en) | Preparation method and quality control method for medicinal preparation for treating women climacteric syndrome | |
| CN102743523A (en) | Production process of traditional Chinese medicine for treating anhypnia | |
| CN1843461A (en) | Pharmaceutical composition, its preparation method and quality control method | |
| CN102178891B (en) | Chinese medicinal dispersible tablets for treating gastritis and preparation method thereof | |
| CN108704049B (en) | Traditional Chinese medicine composition with antioxidant function and preparation method of health food thereof | |
| CN102233089B (en) | Traditional Chinese medicine composition and preparation method thereof | |
| CN107095979B (en) | Traditional Chinese medicine composition suitable for treating hyperlipidemia, preparation method and application thereof | |
| CN112603973A (en) | Improved preparation method of pharmaceutical composition for treating lung cough | |
| CN105748628A (en) | Traditional Chinese medicine soluble powder for treating piglet diarrhea | |
| WO2019205959A1 (en) | Pharmaceutical composition for treating epilepsy and convulsions, infantile convulsions and facial spasms and preparation method therefor | |
| CN109646405A (en) | A kind of monkey mushroom granule and preparation method thereof | |
| CN109568468A (en) | A kind of dye yam granule and preparation method thereof | |
| CN111388584A (en) | Composition for treating impotence and preparation method thereof | |
| CN110664903A (en) | Composition with blood fat reducing function and preparation method and application 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 |