CN1583125A - Oral disintegrants of quick acting on heart and their preparation - Google Patents
Oral disintegrants of quick acting on heart and their preparation Download PDFInfo
- Publication number
- CN1583125A CN1583125A CN 200410045596 CN200410045596A CN1583125A CN 1583125 A CN1583125 A CN 1583125A CN 200410045596 CN200410045596 CN 200410045596 CN 200410045596 A CN200410045596 A CN 200410045596A CN 1583125 A CN1583125 A CN 1583125A
- Authority
- CN
- China
- Prior art keywords
- weight portion
- oral cavity
- ethanol
- clathrate
- tablet according
- 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.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims description 26
- 239000007884 disintegrant Substances 0.000 title 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 58
- 208000019622 heart disease Diseases 0.000 claims abstract description 37
- 230000002378 acidificating effect Effects 0.000 claims abstract description 24
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims abstract description 18
- 210000000214 mouth Anatomy 0.000 claims description 45
- 238000002481 ethanol extraction Methods 0.000 claims description 18
- 238000000605 extraction Methods 0.000 claims description 18
- 239000000284 extract Substances 0.000 claims description 15
- 239000012567 medical material Substances 0.000 claims description 13
- 238000010828 elution Methods 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- -1 filter Substances 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 11
- 238000000194 supercritical-fluid extraction Methods 0.000 claims description 11
- 238000012856 packing Methods 0.000 claims description 10
- 239000011347 resin Substances 0.000 claims description 10
- 229920005989 resin Polymers 0.000 claims description 10
- 239000003463 adsorbent Substances 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 239000000706 filtrate Substances 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 230000001351 cycling effect Effects 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 239000000469 ethanolic extract Substances 0.000 claims description 6
- 239000000796 flavoring agent Substances 0.000 claims description 6
- 235000019634 flavors Nutrition 0.000 claims description 6
- 239000008187 granular material Substances 0.000 claims description 6
- 238000005469 granulation Methods 0.000 claims description 6
- 230000003179 granulation Effects 0.000 claims description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- 239000007916 tablet composition Substances 0.000 claims description 6
- 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 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 4
- 125000002057 carboxymethyl group Chemical class [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 4
- 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 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 3
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 3
- 239000001913 cellulose Substances 0.000 claims description 3
- 235000010980 cellulose Nutrition 0.000 claims description 3
- 229920002678 cellulose Polymers 0.000 claims description 3
- 239000000945 filler Substances 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 239000013081 microcrystal Substances 0.000 claims description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 3
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 3
- 229940013618 stevioside Drugs 0.000 claims description 3
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims description 3
- 235000019202 steviosides Nutrition 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical class OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 238000001179 sorption measurement Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 10
- 229920000858 Cyclodextrin Polymers 0.000 abstract description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 abstract description 2
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 abstract 2
- 229940116229 borneol Drugs 0.000 abstract 2
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 abstract 2
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 abstract 2
- 239000003826 tablet Substances 0.000 description 43
- FINHMKGKINIASC-UHFFFAOYSA-N Tetramethylpyrazine Chemical compound CC1=NC(C)=C(C)N=C1C FINHMKGKINIASC-UHFFFAOYSA-N 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000009982 suxiao jiuxinwan Substances 0.000 description 27
- KSEBMYQBYZTDHS-HWKANZROSA-M (E)-Ferulic acid Natural products COC1=CC(\C=C\C([O-])=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-M 0.000 description 17
- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 description 17
- 229940114124 ferulic acid Drugs 0.000 description 17
- KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 description 17
- 235000001785 ferulic acid Nutrition 0.000 description 17
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 description 17
- 239000000243 solution Substances 0.000 description 12
- 239000004615 ingredient Substances 0.000 description 11
- 238000012360 testing method Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 239000013558 reference substance Substances 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 210000004165 myocardium Anatomy 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 206010021143 Hypoxia Diseases 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000000302 ischemic effect Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 230000010412 perfusion Effects 0.000 description 5
- 230000010410 reperfusion Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- 229940126678 chinese medicines Drugs 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 3
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 3
- 206010002660 Anoxia Diseases 0.000 description 3
- 241000976983 Anoxia Species 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 3
- 229930013930 alkaloid Natural products 0.000 description 3
- 230000007953 anoxia Effects 0.000 description 3
- 230000007954 hypoxia Effects 0.000 description 3
- 238000004811 liquid chromatography Methods 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 2
- 238000012449 Kunming mouse Methods 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 229950006790 adenosine phosphate Drugs 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000011443 conventional therapy Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- 230000000384 rearing effect Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000011003 system suitability test Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- IQVQXVFMNOFTMU-FLIBITNWSA-N (Z)-ligustilide Chemical compound C1CC=CC2=C1C(=C/CCC)/OC2=O IQVQXVFMNOFTMU-FLIBITNWSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N Calcium oxide Chemical compound [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- IQVQXVFMNOFTMU-DHZHZOJOSA-N Z-ligustilide Natural products C1CC=CC2=C1C(=C/CCC)\OC2=O IQVQXVFMNOFTMU-DHZHZOJOSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 229940048102 triphosphoric acid Drugs 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
A Chinese medicine in the form of oral disintegrating tablet for the first aid of heart disease is prepared from Chuan-xiong rhizome and borneol through supercritical extracting, extracting in acidic alcohol, and inclusion with borneol and cyclodextrin.
Description
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to a kind of fast-acting heart disease curing oral cavity disintegration tablet and preparation method thereof.
Technical background
By Rhizoma Chuanxiong and Borneolum Syntheticum is treatment coronary heart disease, the anginal SUXIAO JIUXIN WAN that raw material is made, and goes on the market over more than 20 year, ten million bar life is saved from Death's hands, demonstrates good therapeutical effect.Containing in the Rhizoma Chuanxiong with the ligustrazine is the alkaloids substance of main component, is the volatile material of main component with the ligustilide and is the organic acid substance of main component with the ferulic acid; Application number is the SUXIAO JIUXIN WAN in 85105829 the patent documentation, adopts alcohol extraction, and the acid method acquisition with the chloroform extraction remove impurity of the water liquid furnishing after concentrating is the alkaloid compound of main effective ingredient with ligustrazine; Along with development of times, it is found that ferulic acid contained in the Rhizoma Chuanxiong [Ou Shiyi, etc.The Advance on Pharmacological Activities of ferulic acid and derivant thereof.Chinese crude drug, 2001,24 (3): 220] and volatile material [Lai Fusheng, etc.The influence of Rhizoma Chuanxiong injection to flowing in the platelet calcium.Shanghai Medicine, 1995,18 (3): 157] also has very strong physiologically active; Main effective ingredient ligustrazine instability in the Rhizoma Chuanxiong, 22 ℃ begin distillation, behind sour salify, the stability enhancing [Zhang Likun, etc.Ferulic acid and ligustrazine in the high effective liquid chromatography for measuring compound preparation.Chinese herbal medicine, 1996,27 (4): 213].Ferulic acid stability increase in acid solution [Yang Guangde, etc.The Study on Extraction Method of ferulic acid in the Rhizoma Chuanxiong.Chinese patent medicine, 2002,24 (6): 418].
The patent documentation of application number 01100108 adopts microwave extracting, concentrating under reduced pressure, supersonic jet technology spray drying to extract the effective ingredient in the Rhizoma Chuanxiong; The method cycle is long, and investment is big, and is very undesirable to the extraction that contains unstable material and a large amount of volatile ingredients; Application number is that to adopt the method for alcohol extraction, water extract-alcohol precipitation and application number be that 02123498 patent documentation adopts vapor distillation, rectification for 02135441 patent documentation, method that alcohol extraction, water are carried is extracted the effective ingredient in the Rhizoma Chuanxiong, does not consider that the unstability of ligustrazine and volatile ingredient are heated for a long time and are destroyed and lose.
Documents and materials [former virtue forever, etc.Supercritical fluid CO
2Extraction Rhizoma Chuanxiong volatile oil The Chemical Constituents.Chinese Pharmaceutical Journal, 2000,35 (2): 84] in, adopt the effective ingredient in the supercritical fluid extraction Rhizoma Chuanxiong.Find by testing us, carry agent, still can detect a large amount of ligustrazine and ferulic acid in the medicinal residues, this shows that supercritical extraction extracts very incomplete to polarity bigger alkaloid and organic acid composition even in supercritical extraction, add.
Oral cavity disintegration tablet is emerging in recent years novel form, and this dosage form need not water and also need not to chew, and medicine places on the tongue, after the rapid disintegrate of chance saliva, borrows swallowing act to go into the stomach onset, also can place the Sublingual, and medicine passes through the mucosa absorption onset after the disintegrate rapidly.
Summary of the invention
The objective of the invention is in order to overcome the deficiency that above-mentioned prior art exists, provide a kind of taking convenience, rapid-action to indication, reach the peak early, the tangible fast-acting heart disease curing orally disintegrating tablet preparation of curative effect and preparation method thereof.
According to raw medicinal material contained effective ingredient and physicochemical property thereof, the present invention adopts the volatile effective component in the supercritical extraction unit extraction Rhizoma Chuanxiong medical material, with the Borneolum Syntheticum enclose; The medicinal residues acidic ethanol extraction, the technology effective component extracting of macroporous adsorbent resin remove impurity; With the pharmaceutic adjuvant combination, be prepared into oral cavity disintegration tablet again.The content of product active ingredient of the present invention significantly increases, and drug effect also is greatly improved, and this is not to be because the effect that the dosage form of oral cavity disintegration tablet itself is brought.
The present invention is achieved through the following technical solutions:
One, process recipes
(1) raw medicinal material of oral cavity disintegration tablet composition weight portion is: Rhizoma Chuanxiong 20-60, Borneolum Syntheticum 1-2
(2) get the Rhizoma Chuanxiong medical material, pulverize, cross the 20-60 mesh sieve, through supercritical extraction, extracting pressure is 10-50Mpa, at 20-70 ℃ of cycling extraction 1-4 hour, obtains supercritical extract;
(3), be twice of the acidic ethanol extraction of 1-6 with the pH value of 60%-95% with above-mentioned medicinal residues; Be equivalent to medical material weight 6-10 solvent doubly each the adding; Extracted 1-3 hour for the first time, extracted 1-2 hour for the second time; Merge ethanol extract, filter, filtrate is concentrated into does not have the alcohol flavor; Last macroporous adsorbent resin, the washing of doubly measuring earlier, reuse 30%-80% ethanol elution with 3-6; Collect ethanol elution, be concentrated into the extractum that relative density is 1.15-1.30 in the time of 50 ℃, obtain the acidic ethanol extraction thing;
(4) supercritical extract, acidic ethanol extraction thing and Borneolum Syntheticum are dissolved with small amount of ethanol, slowly add in β-CD or HP-β-CD aqueous solution, 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, filtered, and obtained clathrate;
(5) preparation prescription of the present invention is: clathrate 5-40 weight portion, disintegrating agent 10-30 weight portion, filler 50-90 weight portion, correctives 1-10 weight portion, lubricant 0.5-3 weight portion;
(6) clathrate is mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain oral cavity disintegration tablet.
Prepared disintegrating tablet is made up of Rhizoma Chuanxiong, Borneolum Syntheticum clathrate 5-40 weight portion and pharmaceutic adjuvant 61.5-133 weight portion, and wherein the Rhizoma Chuanxiong supercritical extract is that 0.5-3.0 weight portion, acidic ethanol extraction thing are the 0.2-0.6 weight portion in the clathrate.
Above-mentioned preparation method is after with the volatile ingredient in the supercritical fluid extraction Rhizoma Chuanxiong, the medicinal residues acidic ethanol extraction, make the easy main effective ingredient ligustrazine that distils exist with the form of stable salt, ferulic acid also has been in and has made in its more stable sour environment, thereby avoided ligustrazine and ferulic acid losing because of being heated in the leaching process for a long time, increased extracted amount, pass through cyclodextrin inclusion compound again, further consolidate stability of drug, the disintegrating tablet made of adjuvant is in use in addition again, shorten pharmaceutical release time, increase dissolution, can reach drug effect more fast.
Two, assay analysis
1. high effective liquid chromatography for measuring is rescued the content of ligustrazine in the heart preparation
1.1 instrument and reagent high performance liquid chromatograph comprise LC-10ATvp type solvent delivery pump, SPD-10ATvp type UV, visible light detector (day island proper Tianjin company); N2000 chromatographic work station (Zhejiang University's intelligent information Graduate School of Engineering); KQ3200 type ultrasonic washing instrument (Kunshan Ultrasonic Instruments Co., Ltd.), TGL-16G high speed tabletop centrifuge (Anting Scientific Instrument Factory, Shanghai).Chromatographically pure methanol (Beijing chemical reagent company limited); Water is tri-distilled water (self-control); Other reagent is analytical pure.SUXIAO JIUXIN WAN (Tianjin No.6 Chinese Medicines Factory); Fast-acting heart disease curing oral cavity disintegration tablet (Qianluchun Science and Technology Co., Ltd., Beijing's laboratory provides); Ligustrazine reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute).
1.2 chromatographic condition and system suitability test chromatographic column: the C of Di Ma company
18Post (5 μ m, 150mm * 4.6mm, I.D); Mobile phase: methanol-0.1mol/L acetic acid, sodium-acetate buffer (33: 47) [pH4.0]; Flow velocity: 1.0ml/min detects wavelength: 278nm.Number of theoretical plate should be not less than 3000 by ligustrazine peak compute.
Take by weighing ligustrazine reference substance 4.00mg 1.3 reference substance solution prepares precision, insert in the 200ml measuring bottle, add methanol, ultrasonicly make dissolving, add methanol again to scale, promptly.
1.4 accurate respectively above-mentioned reference substance solution 1 μ l, 5 μ l, 10 μ l, 15 μ l, the 20 μ l of drawing of standard curve preparation, sample introduction is measured under the said determination condition, ligustrazine is the good linear relation in 0.02 μ g～0.40 μ g scope as a result, and regression equation is Y=1.0798 * 10
-3X+0.019836, r=0.9998.
1.5 10 of test samples are got in the preparation of need testing solution, the accurate title, decided porphyrize, get 0.5g, the accurate title, decide, and puts in the tool plug conical flask, the accurate methanol 10ml that adds claims to decide weight, supersound process 1 hour, put coldly, claim again to decide weight, supply the weight that subtracts mistake with methanol, shake up, filter, get subsequent filtrate centrifugal (12000rpm) 10min, supernatant is as need testing solution.
1.6 accurate each the 10 μ l of need testing solution that draw of algoscopy inject chromatograph of liquid, measure peak area, calculate content with standard curve.The results are shown in Table 1.
Ligustrazine content relatively in table 1 preparation
The group ligustrazine
*
(mg)
SUXIAO JIUXIN WAN 11.88
The fast-acting heart disease curing oral cavity collapses 14.43
Separate sheet
*Represent one time dose
Annotate: the each dose of fast-acting heart disease curing oral cavity disintegration tablet of the present invention is 3.
2. high effective liquid chromatography for measuring is rescued content of ferulic acid in the heart preparation
2.1 instrument and reagent high performance liquid chromatograph comprise LC-10ATvp type solvent delivery pump, SPD-10ATvp type UV, visible light detector (day island proper Tianjin company); N2000 chromatographic work station (Zhejiang University's intelligent information Graduate School of Engineering); KQ3200 type ultrasonic washing instrument (Kunshan Ultrasonic Instruments Co., Ltd.), TGL-16G high speed tabletop centrifuge (Anting Scientific Instrument Factory, Shanghai).Chromatographically pure methanol (Beijing chemical reagents corporation); Water is tri-distilled water (self-control); Other reagent is analytical pure.SUXIAO JIUXIN WAN (Tianjin No.6 Chinese Medicines Factory); Fast-acting heart disease curing oral cavity disintegration tablet (Qianluchun Science and Technology Co., Ltd., Beijing's laboratory provides); Ferulic acid reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute).
2.2 chromatographic condition and system suitability test chromatographic column: the C of Di Ma company
18Post (5 μ m, 150mm * 4.6mm, I.D); Mobile phase: methanol-1% acetic acid (35: 65); Flow velocity: 1.0ml/min; Detect wavelength 313nm; Number of theoretical plate should be not less than 3000 by ferulic acid peak compute.
2.3 reference substance mixed solution preparation precision takes by weighing the about 3mg of ferulic acid reference substance, puts in the 100mL measuring bottle, adding methanol ultrasonicly makes dissolving, adds methanol again to scale, shakes up, promptly.
2.4 the ferulic acid reference substance solution of variable concentrations is prepared in the standard curve preparation respectively, sample introduction is measured under the said determination condition.The result shows, ferulic acid sample size and peak area in 0.0775 μ g～0.620 μ g scope are the good linear relation, and linear equation is Y=909.8X-16498, r=0.9995.
2.5 10 of test samples are got in the preparation of need testing solution, the accurate title, decided porphyrize, get 0.5g, the accurate title, decide, and puts in the tool plug conical flask, the accurate methanol 10ml that adds claims to decide weight, supersound process 1 hour, put coldly, claim again to decide weight, supply the weight that subtracts mistake with methanol, shake up, get supernatant liquid filtering, get subsequent filtrate, promptly.
2.6 accurate each the 10 μ l of need testing solution that draw of algoscopy inject chromatograph of liquid, measure peak area, calculate content with standard curve.The results are shown in Table 2.
Ferulaic acid content relatively in table 2 preparation
Group ferulic acid *
(mg)
SUXIAO JIUXIN WAN 12.29
Fast-acting heart disease curing oral cavity 26.64
Disintegrating tablet
*Represent one time dose
Conclusion: above assay description of test, effective ingredient ligustrazine, content of ferulic acid in the fast-acting heart disease curing oral cavity disintegration tablet of the present invention all increase, and fast-acting heart disease curing oral cavity disintegration tablet bioavailability of the present invention is higher, proves absolutely that preparation technology of the present invention has practical significance.
Three, disintegration
Get fast-acting heart disease curing oral cavity disintegration tablet of the present invention, place the beaker of the 10ml that fills 37 ℃ of water of 5ml, stir with 30 rev/mins speed.The whole disintegrates in 40 seconds of result's oral cavity disintegration tablet of the present invention are also sieved by No. 2.
Four, dissolution experiment
4.1 instrument and the full-automatic digestion instrument of reagent SR-6 type (U.S. Hanson company); Distilled water (self-control); SUXIAO JIUXIN WAN (Tianjin No.6 Chinese Medicines Factory); Fast-acting heart disease curing oral cavity disintegration tablet (Qianluchun Science and Technology Co., Ltd., Beijing's laboratory provides).
4.2 experimental technique is pressed in the dissolution method (" two appendix XC of Chinese pharmacopoeia version in 2000) second method and is measured.Each container fills the distilled water through degassing processing of 100ml, and heating makes water temperature remain on 37 ℃ ± 0.5 ℃, and rotating speed of agitator is 50 rev/mins.Put into 1 of fast-acting heart disease curing oral cavity disintegration tablet of the present invention, take out 2ml solution at regular intervals, centrifugal 10 minutes (12000rpm), supernatant measure ligustrazine content as need testing solution with above-mentioned content assaying method.The results are shown in Table 3.
The dissolution of two kinds of medicines of table 3 relatively
Medicine sample time (min)
0.5 1 2 4 8 12 16 20
SUXIAO JIUXIN WAN 4.96 5.28 6.42 7.63 8.84 9.13 10.49 11.88
Fast-acting heart disease curing oral cavity disintegration tablet 8.73 9.42 10.77 11.96 12.18 13.33 14.43 14.43
Conclusion: fast-acting heart disease curing oral cavity disintegration tablet 0.5min, dissolution rate can reach more than 50%, complete stripping in 16 minutes; Just stripping is complete and the dissolution rate of SUXIAO JIUXIN WAN 0.5min has only 42%, 20 minute.Therefore, fast-acting heart disease curing oral cavity disintegration tablet of the present invention has produce effects characteristics rapidly.
Five, pharmacology embodiment
5.1 influence experiment to anoxia in mice endurance
Get 30 of healthy Kunming mouses, body weight 20～24g.Be divided into matched group at random, SUXIAO JIUXIN WAN group, fast-acting heart disease curing oral cavity disintegration tablet group.Every group 10, male and female half and half, sub-cage rearing.With the conversion of people's conventional therapy dosage is the dosage of mice.The conversion formula is: tested animal is tried out the body surface area ratio of the body surface area ratio/known animal of dosage=known animals administer amount * tested animal.Control group administered physiological saline, 1 time/d, continuous 13d.1h after the last administration, it is the 150ml port grinding bottle that mice is placed volume respectively, in put the 15g sodica calx, its time-to-live of airtight observation.The results are shown in Table 4.
The influence of table 4 pair mice normobaric hypoxia (X ± SD)
Group Mus number (only) mean survival time (min)
Matched group 10 19.14 ± 2.36
SUXIAO JIUXIN WAN group 10 24.74 ± 2.23
*
Fast-acting heart disease curing oral cavity disintegration tablet group 10 28.62 ± 2.77
*#
Annotate: compare with matched group:
*P＜0.01;
Compare with the SUXIAO JIUXIN WAN group: #P＜0.05
SUXIAO JIUXIN WAN, fast-acting heart disease curing oral cavity disintegration tablet all can improve mice normobaric hypoxia endurance, and mean survival time is than matched group significant prolongation (P＜0.01); The fast-acting heart disease curing oral cavity disintegration tablet is compared with SUXIAO JIUXIN WAN, mean survival time also variant (P＜0.05).Illustrate: fast-acting heart disease curing oral cavity disintegration tablet and SUXIAO JIUXIN WAN can significantly improve mice normobaric hypoxia endurance, and the effect of fast-acting heart disease curing oral cavity disintegration tablet is better than SUXIAO JIUXIN WAN.
5.2 to the anoxybiotic protective effect experiment of mouse cardiac muscle
Get 30 of healthy Kunming mouses, body weight 18～22g is divided into 3 groups at random, matched group, SUXIAO JIUXIN WAN group, fast-acting heart disease curing oral cavity disintegration tablet group.Every group of male and female half and half, sub-cage rearing.With the conversion of people's conventional therapy dosage is the dosage of mice.The conversion formula is: tested animal is tried out the body surface area ratio of the body surface area ratio/known animal of dosage=known animals administer amount * tested animal.Control group administered physiological saline.Medication: 1 time/d, continuous 6d.1h is with urethane 1.2g/kg intraperitoneal injection of anesthesia after the last administration, and back fixation is separated trachea, with the bulldog clamp folder pipe of holding one's breath, observes electrocardio with electrocardiogram equipment, and writes down the little mousetrap with stopwatch and hold one's breath time of Guan Houzhi electrocardio disappearance.The results are shown in Table 5.
The anoxybiotic influence of table 5 pair mouse cardiac muscle (X ± SD)
Group Mus number (only) mean survival time (min)
Matched group 10 6.26 ± 0.68
SUXIAO JIUXIN WAN group 10 7.88 ± 0.49*
Fast-acting heart disease curing oral cavity disintegration tablet group 10 9.07 ± 0.57*#
Annotate: compare with matched group:
*P＜0.01;
Compare with the SUXIAO JIUXIN WAN group: #P＜0.05
SUXIAO JIUXIN WAN, fast-acting heart disease curing oral cavity disintegration tablet all can shield to the mouse cardiac muscle anoxia, and mean survival time is than matched group significant prolongation (P＜0.01); The fast-acting heart disease curing oral cavity disintegration tablet is compared with SUXIAO JIUXIN WAN, mean survival time also variant (P＜0.05).Illustrate: fast-acting heart disease curing oral cavity disintegration tablet and SUXIAO JIUXIN WAN can shield to the mouse cardiac muscle anoxia, and the effect of fast-acting heart disease curing oral cavity disintegration tablet is better than SUXIAO JIUXIN WAN.
5.3 influence to ischemia/reperfusion injury cardiac muscle high-energy phosphate compound
Adopt Langendorff isolated heart perfusion technology, preparation myocardial ischemia model utilizes high performance liquid chromatography (HPLC) to measure the changes of contents of the high-energy phosphate compound in the isolated rat cardiac muscular tissue.Be divided into 4 groups: the normal control group: rat heart is connected on continous perfusion 75min on the perfusion device after exsomatizing.The ischemic reperfusion group: the pre-earlier 15min that irritates, stop perfusion then, keep the heart temperature constant at 37 ℃, the condition underlying 40min at anaerobic, no perfusate recovers perfusion 20min again.SUXIAO JIUXIN WAN protection group: add quick-acting pills for curing heart disease when irritating in advance, post processing is with the ischemic reperfusion group.Fast-acting heart disease curing oral cavity disintegration tablet protection group: add the quick-acting pit of the stomach cavity disintegrating tablets of rescuing when irritating in advance, post processing is with the ischemic reperfusion group.The results are shown in Table 6.
The influence of table 6 pair ischemia/reperfusion injury cardiac muscle high-energy phosphate compound (X ± SD)
Group adenylic acid total amount (μ g/100mg)
Normal control group 95.42 ± 11.37
Ischemic reperfusion group 20.88 ± 4.86
SUXIAO JIUXIN WAN protection group 64.64 ± 7.92*
Fast-acting heart disease curing oral cavity disintegration tablet protection group 82.03 ± 5.22*#
Annotate: compare with the ischemic reperfusion group:
*P＜0.01;
Compare with the SUXIAO JIUXIN WAN group: #P＜0.05
Adenylic acid total amount=adenosine monophosphate (AMP)+adenosine diphosphate (ADP) (ADP)+triphosphoric acid glycosides (ATP)
Fast-acting heart disease curing oral cavity disintegration tablet, SUXIAO JIUXIN WAN all can improve ischemic myocardium energy reserve ability, and the effect of fast-acting heart disease curing oral cavity disintegration tablet is better than SUXIAO JIUXIN WAN.
Above pharmacological evaluation proves that the fast-acting heart disease curing oral cavity disintegration tablet for preparing with new technology has better therapeutic effect than SUXIAO JIUXIN WAN.
Six, preparation embodiment
Embodiment 1
(1) raw medicinal material of disintegrating tablet composition weight portion is: Rhizoma Chuanxiong 22g Borneolum Syntheticum 1.8g
(2) get the Rhizoma Chuanxiong medical material, pulverize, cross 20 mesh sieves, in the extraction kettle of the supercritical extraction unit of packing into, at 12Mpa, 60 ℃ of cycling extractions 2 hours obtain supercritical extract 0.76;
(3) with above-mentioned medicinal residues, the acidic ethanol of the pH5.5 with 90% is made solvent and is extracted twice with multi-functional extractor; Each solvent that is equivalent to 6 times of medical material weight that adds; Extracted 2 hours for the first time, extracted 1 hour for the second time; Merge ethanol extract, filter, filtrate is concentrated into does not have the alcohol flavor; Last macroporous adsorbent resin, first washing, reuse 80% ethanol elution with 6 times of amounts; Collect ethanol elution, be concentrated into relative density in the time of 50 ℃ and be 1.20 extractum, obtain acidic ethanol extraction thing 0.23g;
(4) supercritical extract, acidic ethanol extraction thing and Borneolum Syntheticum are dissolved with small amount of ethanol, slowly add in HP-β-CD aqueous solution, 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, filtered, and obtained clathrate 11g;
(5) preparation prescription is:
Clathrate 11g
Nano micro crystal cellulose 85g
Low-substituted hydroxypropyl methylcellulose 20g
Mannitol 2.5g
Magnesium stearate 1.5g
(6) clathrate is mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain oral cavity disintegration tablet.
Embodiment 2
(1) raw medicinal material of disintegrating tablet composition weight portion is: Rhizoma Chuanxiong 30g Borneolum Syntheticum 1.6g
(2) get the Rhizoma Chuanxiong medical material, pulverize, cross 40 mesh sieves, in the extraction kettle of the supercritical extraction unit of packing into, at 25Mpa, 50 ℃ of cycling extractions 1.5 hours obtain supercritical extract 1.14g;
(3) with above-mentioned medicinal residues, the acidic ethanol of the pH4 with 80% is made solvent and is extracted twice with multi-functional extractor; Each solvent that is equivalent to 8 times of medical material weight that adds; Extracted 3 hours for the first time, extracted 2 hours for the second time; Merge ethanol extract, filter, filtrate is concentrated into does not have the alcohol flavor; Last macroporous adsorbent resin, first washing, reuse 40% ethanol elution with 3 times of amounts; Collect ethanol elution, be concentrated into relative density in the time of 50 ℃ and be 1.23 extractum, obtain acidic ethanol extraction thing 0.42g;
(4) supercritical extract, acidic ethanol extraction thing and Borneolum Syntheticum are dissolved with small amount of ethanol, slowly add in β-CD aqueous solution, 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, filtered, and obtained clathrate 25g;
(5) preparation prescription is:
Clathrate 25g
Microcrystalline Cellulose 76g
Carboxymethyl starch sodium 14g
Mannitol 3.6g
Pulvis Talci 1.4g
(6) clathrate is mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain oral cavity disintegration tablet.
Embodiment 3
(1) raw medicinal material of disintegrating tablet composition weight portion is: Rhizoma Chuanxiong 46g Borneolum Syntheticum 1.5g
(2) get the Rhizoma Chuanxiong medical material, pulverize, cross 30 mesh sieves, in the extraction kettle of the supercritical extraction unit of packing into, at 40Mpa, 40 ℃ of cycling extractions 3 hours obtain supercritical extract 1.96g;
(3) with above-mentioned medicinal residues, the acidic ethanol of the pH4 with 75% is made solvent and is extracted twice with multi-functional extractor; Each solvent that is equivalent to 10 times of medical material weight that adds; Extracted 2 hours for the first time, extracted 1 hour for the second time; Merge ethanol extract, filter, filtrate is concentrated into does not have the alcohol flavor; Last macroporous adsorbent resin, first washing, reuse 60% ethanol elution with 4 times of amounts; Collect ethanol elution, be concentrated into relative density in the time of 50 ℃ and be 1.30 extractum, obtain acidic ethanol extraction thing 0.57g;
(4) supercritical extract, acidic ethanol extraction thing and Borneolum Syntheticum are dissolved with small amount of ethanol, slowly add in β-CD aqueous solution, 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, filtered, and obtained clathrate 32g;
(5) preparation prescription is:
Clathrate 32g
Nano micro crystal cellulose 64g
Crosslinked carboxymethyl fecula sodium 19g
Stevioside 3.4g
Stepanol MG 1.6g
(6) clathrate is mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain oral cavity disintegration tablet.
Embodiment 4
(1) raw medicinal material of disintegrating tablet composition weight portion is: Rhizoma Chuanxiong 58g Borneolum Syntheticum 1.1g
(2) get the Rhizoma Chuanxiong medical material, pulverize, cross 60 mesh sieves, in the extraction kettle of the supercritical extraction unit of packing into, at 50Mpa, 30 ℃ of cycling extractions 4 hours obtain supercritical extract 2.77g;
(3) with above-mentioned medicinal residues, the acidic ethanol of the pH3 with 60% is made solvent and is extracted each solvent that is equivalent to 8 times of medical material weight that adds twice with multi-functional extractor; Extracted 3 hours for the first time, extracted 2 hours for the second time; Merge ethanol extract, filter, filtrate is concentrated into does not have the alcohol flavor; Last macroporous adsorbent resin, first washing, reuse 70% ethanol elution with 5 times of amounts; Collect ethanol elution, be concentrated into relative density in the time of 50 ℃ and be 1.27 extractum, obtain acidic ethanol extraction thing 0.35g;
(4) supercritical extract, acidic ethanol extraction thing and Borneolum Syntheticum are dissolved with small amount of ethanol, slowly add in HP-β-CD aqueous solution, 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, filtered, and obtained clathrate 38g;
(5) preparation prescription is:
Clathrate 38g
Microcrystalline Cellulose 51g
Crospolyvinylpyrrolidone 26g
Stevioside 3g
Magnesium stearate 2g
(6) clathrate is mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain oral cavity disintegration tablet.
Claims (9)
1. fast-acting heart disease curing oral cavity disintegration tablet, it is characterized in that it is made up of Rhizoma Chuanxiong, Borneolum Syntheticum clathrate 5-40 weight portion and pharmaceutic adjuvant 61.5-133 weight portion, wherein the Rhizoma Chuanxiong supercritical extract is that 0.5-3.0 weight portion, acidic ethanol extraction thing are the 0.2-0.6 weight portion in the clathrate.
2. a kind of fast-acting heart disease curing oral cavity disintegration tablet according to claim 1, its preparation method may further comprise the steps:
(1) raw medicinal material of disintegrating tablet composition weight portion is: Rhizoma Chuanxiong 20-60 Borneolum Syntheticum 1-2;
(2) get the Rhizoma Chuanxiong medical material, pulverize, cross the 20-60 mesh sieve, through supercritical extraction, extracting pressure at 20-70 ℃ of cycling extraction 1-4 hour, obtains supercritical extract at 10-50Mpa;
(3), be twice of the acidic ethanol extraction of 1-6 with the pH value of 60%-95% with above-mentioned medicinal residues; Be equivalent to medical material weight 6-10 solvent doubly each the adding; Extracted 1-3 hour for the first time, extracted 1-2 hour for the second time; Merge ethanol extract, filter, filtrate is concentrated into does not have the alcohol flavor; Last macroporous adsorbent resin, the washing of doubly measuring earlier, reuse 30%-80% ethanol elution with 3-6; Collect ethanol elution, be concentrated into the extractum that relative density is 1.15-1.30 in the time of 50 ℃, obtain the acidic ethanol extraction thing;
(4) supercritical extract, acidic ethanol extraction thing and Borneolum Syntheticum are dissolved with small amount of ethanol, slowly add in β-CD or HP-β-CD aqueous solution, 50 ℃ were stirred 3 hours, continued under the room temperature to stir 5 hours, filtered, and obtained clathrate;
(5) preparation prescription of the present invention is: clathrate 5-40 weight portion, disintegrating agent 10-30 weight portion, filler 50-90 weight portion, correctives 1-10 weight portion, lubricant 0.5-3 weight portion;
(6) clathrate is mixed with pharmaceutic adjuvant, granulation, drying, granulate, tabletting, check, packing obtain oral cavity disintegration tablet.
3. disintegrating tablet according to claim 2, wherein the used acid of acidify ethanol is a kind of in hydrochloric acid, the phosphoric acid.
4. disintegrating tablet according to claim 2, wherein the pH value of acidic ethanol is 3-5.
5. disintegrating tablet according to claim 2, wherein macroporous adsorbent resin is nonpolar macroporous adsorption resin or low pole macroporous adsorbent resin.
6. disintegrating tablet according to claim 2, wherein disintegrating agent is a kind of in low-substituted hydroxypropyl methylcellulose, carboxymethyl starch sodium, crosslinked carboxymethyl fecula sodium or the crospolyvinylpyrrolidone.
7. disintegrating tablet according to claim 2, wherein filler is a kind of in microcrystalline Cellulose or the nano micro crystal cellulose.
8. disintegrating tablet according to claim 2, wherein correctives is a kind of in mannitol or the stevioside.
9. disintegrating tablet according to claim 2, wherein lubricant is a kind of in magnesium stearate or Pulvis Talci or the Stepanol MG.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410045596 CN1583125A (en) | 2004-06-11 | 2004-06-11 | Oral disintegrants of quick acting on heart and their preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410045596 CN1583125A (en) | 2004-06-11 | 2004-06-11 | Oral disintegrants of quick acting on heart and their preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1583125A true CN1583125A (en) | 2005-02-23 |
Family
ID=34601895
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410045596 Pending CN1583125A (en) | 2004-06-11 | 2004-06-11 | Oral disintegrants of quick acting on heart and their preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1583125A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103768348A (en) * | 2012-10-24 | 2014-05-07 | 贵州益佰制药股份有限公司 | Pharmaceutical composition and medicinal preparation used for treating cardiovascular and cerebrovascular diseases, and applications and preparation method thereof |
| CN109394714A (en) * | 2018-12-28 | 2019-03-01 | 海南海药本草生物科技有限公司 | A kind of buccal tablet and preparation method thereof containing kapur |
| CN116059396A (en) * | 2021-11-04 | 2023-05-05 | 西南大学 | Inclusion method of ligusticum chuanxiong hort alcohol extract |
-
2004
- 2004-06-11 CN CN 200410045596 patent/CN1583125A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103768348A (en) * | 2012-10-24 | 2014-05-07 | 贵州益佰制药股份有限公司 | Pharmaceutical composition and medicinal preparation used for treating cardiovascular and cerebrovascular diseases, and applications and preparation method thereof |
| CN109394714A (en) * | 2018-12-28 | 2019-03-01 | 海南海药本草生物科技有限公司 | A kind of buccal tablet and preparation method thereof containing kapur |
| CN116059396A (en) * | 2021-11-04 | 2023-05-05 | 西南大学 | Inclusion method of ligusticum chuanxiong hort alcohol extract |
| CN116059396B (en) * | 2021-11-04 | 2025-07-15 | 西南大学 | A method for inclusion of chuanxiong alcohol extract |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101028348A (en) | Chinese medicinal capsule, its production and quality controlling method | |
| CN1583125A (en) | Oral disintegrants of quick acting on heart and their preparation | |
| CN1118471C (en) | Medicine containing tan matter caesalpinia extract | |
| CN1582952A (en) | Use of asiaticoside in preparation of medicines for diseases of cardio-cerebral blood vessels | |
| CN1586492A (en) | Medicinal composition containing danshensu, total ara-saponin and camphol and its preparation and use | |
| CN1175818C (en) | Extractive preparation containing total alkali of mulberry leaves and its preparing method | |
| CN1296089C (en) | Zedoary injection preparation and its preparing method | |
| CN1271995C (en) | Orally disintegrating tablet of 'Xintongning' and its preparation | |
| CN1562292A (en) | Injection of still-freeze drying powder for restoring consciousness and new preparation method | |
| CN1259099C (en) | Prepared traditional Chinese drug Liangfu drop pills for treating epigastric pain | |
| CN1278705C (en) | Orally disintegrating tablet of 'Tongxinluo' and its preparation | |
| CN1220510C (en) | Chinese patent medicine with the functions of replenishing qi and blood and nourishing the heart to calm the mind, its preparation method and quality control method | |
| CN1259037C (en) | Orally disintegrating tablet of antiviral medicine and its preparation process | |
| CN1286480C (en) | Oral disintegrants of composite salvia miltiorrhiza and their preparation | |
| CN1176677C (en) | Chinese medicine composition for treating cardiovascular and cerebrovascular diseases and its preparing process | |
| CN1583133A (en) | Effervescent tablets for bone diseases and their preparation | |
| CN1628649A (en) | Pharmaceutical combination containing red sage root element and preparation method thereof | |
| CN1563075A (en) | Method of preparing general phenolic acid of red sange root for treating hepatic fibrosis | |
| CN1297278C (en) | Medicinal composition containing salvianolic acid B, total ara-saponin and camphol and its preparation and use | |
| CN1277550C (en) | Wild chrysanthemum oral disintegration tablet and its preparing method | |
| CN1823982A (en) | Chinese medicinal preparation for liver soothing and speen fortifying and its manufacturing method | |
| CN1313103C (en) | Orally disintegrating tablet of bupleurum root and its preparation | |
| CN1616024A (en) | Shengmai powder injection and shengmai chewing tablet and its producing process | |
| CN1891266A (en) | Chinese medicine oral disintegrating tablet for treating angina pectoris, and its preparing method | |
| CN1281206C (en) | Orally disintegrating tablet of 'Xinxuekang |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| AD01 | Patent right deemed abandoned | ||
| C20 | Patent right or utility model deemed to be abandoned or is abandoned |