CN101085018B - Traditional Chinese medicinal composition containing red sage root, notoginseng, radix astragali and borneol or storax and its preparation - Google Patents
Traditional Chinese medicinal composition containing red sage root, notoginseng, radix astragali and borneol or storax and its preparation Download PDFInfo
- Publication number
- CN101085018B CN101085018B CN2006100142629A CN200610014262A CN101085018B CN 101085018 B CN101085018 B CN 101085018B CN 2006100142629 A CN2006100142629 A CN 2006100142629A CN 200610014262 A CN200610014262 A CN 200610014262A CN 101085018 B CN101085018 B CN 101085018B
- Authority
- CN
- China
- Prior art keywords
- ultrafiltration
- adjuvant
- film
- alcohol
- radix
- 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
- 235000003143 Panax notoginseng Nutrition 0.000 title claims abstract description 76
- 241000180649 Panax notoginseng Species 0.000 title claims abstract description 76
- 239000000203 mixture Substances 0.000 title claims abstract description 48
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- 239000009636 Huang Qi Substances 0.000 title claims description 57
- 240000007164 Salvia officinalis Species 0.000 title abstract description 5
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 title description 34
- 235000005412 red sage Nutrition 0.000 title description 4
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 title 1
- 241001060310 Styracaceae Species 0.000 title 1
- 235000001361 Styrax officinalis Nutrition 0.000 title 1
- 229940116229 borneol Drugs 0.000 title 1
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 title 1
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 title 1
- 235000019382 gum benzoic Nutrition 0.000 title 1
- 238000000108 ultra-filtration Methods 0.000 claims abstract description 254
- 239000006187 pill Substances 0.000 claims abstract description 97
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 96
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 90
- 235000015511 Liquidambar orientalis Nutrition 0.000 claims abstract description 42
- 239000000284 extract Substances 0.000 claims abstract description 35
- 238000011282 treatment Methods 0.000 claims abstract description 12
- 239000007788 liquid Substances 0.000 claims description 151
- 239000002671 adjuvant Substances 0.000 claims description 127
- 239000003814 drug Substances 0.000 claims description 124
- 238000000034 method Methods 0.000 claims description 73
- -1 polyoxyethylene monostearate Polymers 0.000 claims description 72
- 239000012528 membrane Substances 0.000 claims description 59
- 239000000243 solution Substances 0.000 claims description 44
- 239000000758 substrate Substances 0.000 claims description 44
- 239000000463 material Substances 0.000 claims description 41
- 241000736148 Styrax Species 0.000 claims description 40
- 239000004870 Styrax Substances 0.000 claims description 40
- 235000000126 Styrax benzoin Nutrition 0.000 claims description 40
- 229940079593 drug Drugs 0.000 claims description 38
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 34
- 239000008101 lactose Substances 0.000 claims description 34
- 229930006000 Sucrose Natural products 0.000 claims description 32
- 239000005720 sucrose Substances 0.000 claims description 32
- 238000000605 extraction Methods 0.000 claims description 29
- 230000000737 periodic effect Effects 0.000 claims description 29
- 235000015073 liquid stocks Nutrition 0.000 claims description 26
- 239000011550 stock solution Substances 0.000 claims description 26
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 24
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 22
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 22
- 239000000811 xylitol Substances 0.000 claims description 22
- 235000010447 xylitol Nutrition 0.000 claims description 22
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 22
- 229960002675 xylitol Drugs 0.000 claims description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 21
- 229920002472 Starch Polymers 0.000 claims description 20
- 230000008569 process Effects 0.000 claims description 20
- 239000008107 starch Substances 0.000 claims description 20
- 235000019698 starch Nutrition 0.000 claims description 20
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 18
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 18
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 18
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 18
- 238000004132 cross linking Methods 0.000 claims description 16
- 235000010489 acacia gum Nutrition 0.000 claims description 15
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims description 15
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 11
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 11
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 10
- 229920006393 polyether sulfone Polymers 0.000 claims description 10
- 239000000377 silicon dioxide Substances 0.000 claims description 10
- 241001597008 Nomeidae Species 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- 229920002239 polyacrylonitrile Polymers 0.000 claims description 9
- 229920001747 Cellulose diacetate Polymers 0.000 claims description 8
- 229920000881 Modified starch Polymers 0.000 claims description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 8
- 235000010418 carrageenan Nutrition 0.000 claims description 8
- 229920001525 carrageenan Polymers 0.000 claims description 8
- 235000012239 silicon dioxide Nutrition 0.000 claims description 8
- 150000005846 sugar alcohols Chemical class 0.000 claims description 8
- 239000002033 PVDF binder Substances 0.000 claims description 7
- 229920002492 poly(sulfone) Polymers 0.000 claims description 7
- 229920002981 polyvinylidene fluoride Polymers 0.000 claims description 7
- 229960001866 silicon dioxide Drugs 0.000 claims description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 6
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 6
- 239000000679 carrageenan Substances 0.000 claims description 6
- 229940113118 carrageenan Drugs 0.000 claims description 6
- 229920002301 cellulose acetate Polymers 0.000 claims description 6
- 229960000502 poloxamer Drugs 0.000 claims description 6
- 229920001983 poloxamer Polymers 0.000 claims description 6
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 6
- 108010010803 Gelatin Proteins 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 239000008273 gelatin Substances 0.000 claims description 5
- 229920000159 gelatin Polymers 0.000 claims description 5
- 229940014259 gelatin Drugs 0.000 claims description 5
- 235000019322 gelatine Nutrition 0.000 claims description 5
- 235000011852 gelatine desserts Nutrition 0.000 claims description 5
- 238000000703 high-speed centrifugation Methods 0.000 claims description 5
- 208000031225 myocardial ischemia Diseases 0.000 claims description 5
- 229910052756 noble gas Inorganic materials 0.000 claims description 5
- 238000001179 sorption measurement Methods 0.000 claims description 5
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 4
- 229920001817 Agar Polymers 0.000 claims description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical group OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 4
- 229920001353 Dextrin Polymers 0.000 claims description 4
- 239000004375 Dextrin Substances 0.000 claims description 4
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 4
- 239000008272 agar Substances 0.000 claims description 4
- 235000010419 agar Nutrition 0.000 claims description 4
- 235000010443 alginic acid Nutrition 0.000 claims description 4
- 239000000783 alginic acid Substances 0.000 claims description 4
- 229920000615 alginic acid Polymers 0.000 claims description 4
- 229960001126 alginic acid Drugs 0.000 claims description 4
- 150000004781 alginic acids Chemical class 0.000 claims description 4
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 4
- 239000004202 carbamide Substances 0.000 claims description 4
- 235000013877 carbamide Nutrition 0.000 claims description 4
- 235000010980 cellulose Nutrition 0.000 claims description 4
- 229920002678 cellulose Polymers 0.000 claims description 4
- 239000001913 cellulose Substances 0.000 claims description 4
- 238000005352 clarification Methods 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- 235000019425 dextrin Nutrition 0.000 claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 4
- 235000013399 edible fruits Nutrition 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 239000000194 fatty acid Substances 0.000 claims description 4
- 229930195729 fatty acid Natural products 0.000 claims description 4
- 150000004665 fatty acids Chemical class 0.000 claims description 4
- 150000002191 fatty alcohols Chemical class 0.000 claims description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 4
- 238000001471 micro-filtration Methods 0.000 claims description 4
- 150000002772 monosaccharides Chemical class 0.000 claims description 4
- 229920001542 oligosaccharide Polymers 0.000 claims description 4
- 150000002482 oligosaccharides Chemical class 0.000 claims description 4
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 claims description 4
- 229920001282 polysaccharide Polymers 0.000 claims description 4
- 239000005017 polysaccharide Substances 0.000 claims description 4
- 150000004804 polysaccharides Chemical class 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
- 235000010356 sorbitol Nutrition 0.000 claims description 4
- 229920000858 Cyclodextrin Polymers 0.000 claims description 3
- 239000004695 Polyether sulfone Substances 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 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 claims description 3
- KXJGSNRAQWDDJT-UHFFFAOYSA-N 1-acetyl-5-bromo-2h-indol-3-one Chemical compound BrC1=CC=C2N(C(=O)C)CC(=O)C2=C1 KXJGSNRAQWDDJT-UHFFFAOYSA-N 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- 229920000178 Acrylic resin Polymers 0.000 claims description 2
- 239000004925 Acrylic resin Substances 0.000 claims description 2
- 229920002101 Chitin Polymers 0.000 claims description 2
- 229920002307 Dextran Polymers 0.000 claims description 2
- 244000286663 Ficus elastica Species 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- 244000275012 Sesbania cannabina Species 0.000 claims description 2
- 229920002125 Sokalan® Polymers 0.000 claims description 2
- 235000004298 Tamarindus indica Nutrition 0.000 claims description 2
- 240000004584 Tamarindus indica Species 0.000 claims description 2
- 229960001631 carbomer Drugs 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 229920000591 gum Polymers 0.000 claims description 2
- 229960001375 lactose Drugs 0.000 claims description 2
- 238000011017 operating method Methods 0.000 claims description 2
- 229920001277 pectin Polymers 0.000 claims description 2
- 239000001814 pectin Substances 0.000 claims description 2
- 235000010987 pectin Nutrition 0.000 claims description 2
- 229960000292 pectin Drugs 0.000 claims description 2
- 229920001721 polyimide Polymers 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 235000002639 sodium chloride Nutrition 0.000 claims description 2
- 229920001285 xanthan gum Polymers 0.000 claims description 2
- 235000010493 xanthan gum Nutrition 0.000 claims description 2
- 239000000230 xanthan gum Substances 0.000 claims description 2
- 229940082509 xanthan gum Drugs 0.000 claims description 2
- 206010063837 Reperfusion injury Diseases 0.000 claims 2
- 229940023476 agar Drugs 0.000 claims 1
- 238000009423 ventilation Methods 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 7
- 238000002156 mixing Methods 0.000 abstract description 6
- 239000000470 constituent Substances 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 abstract 2
- 241000723346 Cinnamomum camphora Species 0.000 abstract 2
- 241000893513 Liquidambar orientalis Species 0.000 abstract 2
- 229940107666 astragalus root Drugs 0.000 abstract 2
- 229960000846 camphor Drugs 0.000 abstract 2
- 229930008380 camphor Natural products 0.000 abstract 2
- 239000001886 liquidambar orientalis Substances 0.000 abstract 2
- 235000017276 Salvia Nutrition 0.000 abstract 1
- 210000003296 saliva Anatomy 0.000 abstract 1
- 238000001914 filtration Methods 0.000 description 73
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 48
- 239000004744 fabric Substances 0.000 description 44
- 239000003921 oil Substances 0.000 description 38
- 235000019198 oils Nutrition 0.000 description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 239000000706 filtrate Substances 0.000 description 32
- 238000005516 engineering process Methods 0.000 description 30
- 238000004140 cleaning Methods 0.000 description 25
- 239000000126 substance Substances 0.000 description 25
- 108090000862 Ion Channels Proteins 0.000 description 24
- 102000004310 Ion Channels Human genes 0.000 description 24
- 230000008859 change Effects 0.000 description 24
- 229940057995 liquid paraffin Drugs 0.000 description 24
- 229910052757 nitrogen Inorganic materials 0.000 description 24
- 239000012141 concentrate Substances 0.000 description 22
- 239000002932 luster Substances 0.000 description 22
- 241000196324 Embryophyta Species 0.000 description 21
- 238000010298 pulverizing process Methods 0.000 description 21
- 241001061264 Astragalus Species 0.000 description 19
- 235000010110 Astragalus glycyphyllos Nutrition 0.000 description 19
- 235000006533 astragalus Nutrition 0.000 description 19
- 238000011001 backwashing Methods 0.000 description 18
- 238000004519 manufacturing process Methods 0.000 description 13
- 239000012567 medical material Substances 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 230000006837 decompression Effects 0.000 description 11
- 238000011160 research Methods 0.000 description 10
- 238000002481 ethanol extraction Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 239000000469 ethanolic extract Substances 0.000 description 7
- 239000008187 granular material Substances 0.000 description 7
- 206010002383 Angina Pectoris Diseases 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 6
- 239000005708 Sodium hypochlorite Substances 0.000 description 6
- 238000000429 assembly Methods 0.000 description 6
- 230000000712 assembly Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000011010 flushing procedure Methods 0.000 description 6
- 239000011259 mixed solution Substances 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 6
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 5
- IPQKDIRUZHOIOM-UHFFFAOYSA-N Oroxin A Natural products OC1C(O)C(O)C(CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IPQKDIRUZHOIOM-UHFFFAOYSA-N 0.000 description 5
- IKIIZLYTISPENI-ZFORQUDYSA-N baicalin Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IKIIZLYTISPENI-ZFORQUDYSA-N 0.000 description 5
- 229960003321 baicalin Drugs 0.000 description 5
- AQHDANHUMGXSJZ-UHFFFAOYSA-N baicalin Natural products OC1C(O)C(C(O)CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 AQHDANHUMGXSJZ-UHFFFAOYSA-N 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 208000010125 myocardial infarction Diseases 0.000 description 5
- 235000002949 phytic acid Nutrition 0.000 description 5
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 229920002545 silicone oil Polymers 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 4
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 4
- 239000004383 Steviol glycoside Substances 0.000 description 4
- PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 4
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 4
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000001212 derivatisation Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 239000006225 natural substrate Substances 0.000 description 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 229940068041 phytic acid Drugs 0.000 description 4
- 239000000467 phytic acid Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 229930182488 steviol glycoside Natural products 0.000 description 4
- 235000019411 steviol glycoside Nutrition 0.000 description 4
- 150000008144 steviol glycosides Chemical class 0.000 description 4
- 235000019202 steviosides Nutrition 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- PVNIQBQSYATKKL-UHFFFAOYSA-N tripalmitin Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC PVNIQBQSYATKKL-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000008899 fufang danshen Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- 210000004165 myocardium Anatomy 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 229920000570 polyether Polymers 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000007670 refining Methods 0.000 description 3
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 2
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- 206010002660 Anoxia Diseases 0.000 description 2
- 241000976983 Anoxia Species 0.000 description 2
- 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 2
- HEBKCHPVOIAQTA-QWWZWVQMSA-N D-arabinitol Chemical compound OC[C@@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-QWWZWVQMSA-N 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 235000011201 Ginkgo Nutrition 0.000 description 2
- 235000008100 Ginkgo biloba Nutrition 0.000 description 2
- 244000194101 Ginkgo biloba Species 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 241000233855 Orchidaceae Species 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 2
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 2
- 150000005215 alkyl ethers Chemical class 0.000 description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 230000007953 anoxia Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 239000000919 ceramic Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000002826 coolant Substances 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000000151 deposition Methods 0.000 description 2
- 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 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- 239000008394 flocculating agent Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000000905 isomalt Substances 0.000 description 2
- 235000010439 isomalt Nutrition 0.000 description 2
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 2
- AMBQHHVBBHTQBF-UOUCRYGSSA-N loganin Chemical compound O([C@@H]1OC=C([C@H]2C[C@H](O)[C@H](C)[C@H]21)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O AMBQHHVBBHTQBF-UOUCRYGSSA-N 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000000419 plant extract Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 2
- 230000010410 reperfusion Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229920002994 synthetic fiber Polymers 0.000 description 2
- 229960001947 tripalmitin Drugs 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 1
- 206010003225 Arteriospasm coronary Diseases 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 206010008469 Chest discomfort Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 241000237970 Conus <genus> Species 0.000 description 1
- 241001269238 Data Species 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- SHWNNYZBHZIQQV-UHFFFAOYSA-J EDTA monocalcium diisodium salt Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-J 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 208000007212 Foot-and-Mouth Disease Diseases 0.000 description 1
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- SQGLUEWZRKIEGS-UHFFFAOYSA-N Ginkgetin Natural products C1=CC(OC)=CC=C1C1=CC(=O)C2=C(O)C=C(OC)C(C=3C(=CC=C(C=3)C=3OC4=CC(O)=CC(O)=C4C(=O)C=3)O)=C2O1 SQGLUEWZRKIEGS-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 229930045534 Me ester-Cyclohexaneundecanoic acid Natural products 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 1
- 239000004353 Polyethylene glycol 8000 Substances 0.000 description 1
- ILRCGYURZSFMEG-UHFFFAOYSA-N Salidroside Natural products OC1C(O)C(O)C(CO)OC1OCCC1=CC=C(O)C=C1 ILRCGYURZSFMEG-UHFFFAOYSA-N 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- 208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 239000012296 anti-solvent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- IYNDLOXRXUOGIU-LQDWTQKMSA-M benzylpenicillin potassium Chemical compound [K+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)CC1=CC=CC=C1 IYNDLOXRXUOGIU-LQDWTQKMSA-M 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 238000004061 bleaching Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 208000005881 bovine spongiform encephalopathy Diseases 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 239000008395 clarifying agent Substances 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000005493 condensed matter Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 208000026758 coronary atherosclerosis Diseases 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000013872 defecation Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 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 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 238000005243 fluidization Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- AIFCFBUSLAEIBR-UHFFFAOYSA-N ginkgetin Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C(C=1)=CC=C(OC)C=1C1=C(O)C=C(O)C(C(C=2)=O)=C1OC=2C1=CC=C(O)C=C1 AIFCFBUSLAEIBR-UHFFFAOYSA-N 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound 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 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000001709 ictal effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000009191 jumping Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 230000003680 myocardial damage Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 210000004681 ovum Anatomy 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
- 229940085678 polyethylene glycol 8000 Drugs 0.000 description 1
- 235000019446 polyethylene glycol 8000 Nutrition 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000003716 rejuvenation Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- ILRCGYURZSFMEG-RQICVUQASA-N salidroside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1OCCC1=CC=C(O)C=C1 ILRCGYURZSFMEG-RQICVUQASA-N 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229940080350 sodium stearate Drugs 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000701 toxic element Toxicity 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- 206010048282 zoonosis Diseases 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a Chinese medicinal composition for treating cardiovascular diseases, which is prepared from root of red rooted saliva, notoginseng, astragalus root, baras camphor or liquidambar orientalis mill as the raw materials, and the preparation process comprises the steps of mixing red-rooted salvia, notoginseng and astragalus root to obtain water extract or alcohol extract, subjecting the extract to preliminary settlement treatment, further subjecting the extract to ultrafiltration treatment, concentrating the ultrafiltrate to obtain concrete, mixing with baras camphor or liquidambar orientalis mill. The invention also discloses preparations using any one of the medicinal compositions as the effective constituents, preferably drop pills.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation thereof of treating cardiovascular disease, particularly relating to a kind of is the pharmaceutical composition of the treatment cardiovascular disease processed of raw material with the Chinese medicine medical material.
Background technology
Along with the rejuvenation of growth in the living standard, world population aging and morbidity colony, cardiovascular and cerebrovascular vessel patient increases year by year, has become the healthy second largest disease of harm humans.Angina pectoris is a kind of caused by the temporary transient ischemia of cardiac muscle, anoxia, serves as the clinical syndrome of main performance with ictal chest pain or chest discomfort.Angina pectoris is meant because coronary atherosclerosis or spasm cause myocardial ischemia, the caused angina pectoris of anoxia, accounts for 90% of patient with angina pectoris.
The anginal method of treatment is main with blood vessel dilating, reduction blood viscosity, antiplatelet aggregation, anticoagulation at present.Traditional Western medicine of using is nitrate, nitrous acid ester, beta-receptor resistance preparation, calcium antagonist etc., but all has bigger toxic and side effects, should not take for a long time, is mostly symptomatic treatment and course of disease progress is not had bigger effect.For example take and occur jumping pain, palpitating speed in feeling of fullness in the head, the head behind the nitroglycerin sometimes, even faint and [, find again in recent years to cause severe hypotension [referring to contemporary Chinese medical journal 1997 referring to new pharmacology [the 14th edition) 264 page]; 7 (4): 42; Shaanxi medical journal 1996; 25 (5): 315], be prone to produce toleration [referring to southern nursing magazine 1996; 3 (5): 7～9] etc. problem has hindered its application clinically.
Though the anginal Chinese patent medicine of many treatments is also arranged, wherein ball, loose, cream, pellet, decoction becomes old historical already, the modern seldom uses.There are preparations such as common compound Salviae Miltiorrhizae tablet and capsule to sell in the market; But conventional tablet, capsule manufacture technology are more backward; Active constituent content is low; Problems such as no quality control standard, therefore, utilize the new treatment cardiovascular disease of new technology development particularly the Chinese medicine of coronary heart disease be the target that vast medical worker makes great efforts.
Membrane separation technique (Membrane Separation Technique) is an emerging high efficient separation technology, by internationally recognized be a most rising great high production tech of mid-term 20 end of the centurys to 21 century.Ultrafiltration (Ultrafiltration, UF) technology is a kind of membrane separation technique, its ultimate principle is to utilize fenestra selectivity sieve performance, with separation, purification and condensed matter.Hyperfiltration process is that the anisotropic membrane (being asymmetric membrane) that utilizes macromolecular material to process is a filter medium, under normal temperature condition, relies on certain pressure and flow velocity, makes flow of solution through face, forces low molecular weight substance to see through film, and polymer substance is trapped.
Because hyperfiltration process is a physical method; Having not must repeated heating; Do not have " phase " to change, the probability of destroying effective ingredient is few than other universal method, characteristics such as technological process weak point; Thereby its be applied to extract in the research of pharmaceutically active ingredient become increasingly active, portioned product moves towards commercial production from laboratory research.Human ultrafiltrations such as 304 Wang Shiling of hospital of PLA are extracted effective ingredient baicalin in the Radix Scutellariae, and the result shows that ultrafiltration is excellent than well-established law all aspect productive rate, purity, and a ultrafiltration can reach the injection requirement; Do not need again row refining; Technology is simple, and the production cycle can shorten 1～2 times of (Wang Shiling, Zheng Dianbao " ultrafiltration is extracted the preliminary investigation of baicalin "; Chinese patent medicine research, 1988 (3): 5).Wang Shiling etc. have also further studied the optimum process condition of ultrafiltration extraction baicalin, and it is the key that improves baicalin yield and quality that the experimental result proof is selected the ultrafilter membrane in suitable aperture (molecular cut off is 6000～10000) for use, the fluid temperature that raises simultaneously or reduction concentration; Strict control pH value (pH=1.5 during acidify; PH=7.0 when alkali dissolves), can significantly improve ultrasiltrated rate, obtain best output effect (Wang Shiling; " ultrafiltration is once extracted the technical study of baicalin "; Chinese patent medicine, 1994,16 (3): 2).Xu Jinlin etc. are used for the preparation of phytic acid with ultrafiltration (PS membrane, molecular cut off 6000), and the phytic acid yield is 86.4%; Improve 12.6% than conventional phytate method, and ultrafiltration gained phytic acid contains Phos hardly, appearance transparent is close to colourless (Xu Jinlin; Xu Jie, Wang Yuanjin " membrane separation technique prepares the research of phytic acid ", Chinese Journal of Pharmaceuticals; 1994,25 (4): 150).He Changsheng etc. use hyperfiltration technique separation and purification steviol glycosides, and adopting ultrathin plate-type hyperfiltration device and molecular cut off is that 10000 CAM (CA film) purifies field experimentation to steviol glycosides, and its technological process is rationally feasible.The ultrafilter stable performance, the decoloration performance and the removal of impurity of film are respond well, bubble problem (He Changsheng in the time of can solving deposition that steviol glycosides usually occurs in producing and embedding preferably; Wang Ping Nan, Zhu Shanshan " applied research of steviol glycosides ultrafiltration ", water technology; 1994,20 (2): 89).Huang is improved oneself and is adopted the refining sasanguasaponin of ultrafilter membrane (molecular cut off is 4000 and 10000 PS membrane), compares with the domestic bleaching that mostly adopts, recrystallize method, the alcohol ether sedimentation method and the basic salt sedimentation method, and the ultrafiltration flow process is simple; Efficient is high, and expense is low, to removing oils and fats, pigment, saccharide and the strong impurity of other hydrophilic in the thick sasanguasaponin; Can both producing a desired effect, (Huang is improved oneself; " ultrafiltrationmembrane process is made with extra care the sasanguasaponin pre-test " water technology, 1995,21 (2): 99).Guo Li Wei of Nanjing University of Traditional Chinese Medicine etc. has relatively studied water alcohol method and ultrafiltration is clarified the influence of Fructus Corni preparation to its preparation ingredient; The result confirms that ultrafiltration is more effective to saccharide impurity in the removal medicinal liquid; Molecular cut off is that 10000 ultrafilter membrane does not have obviously influence to meliatin (molecular weight is 384), makes meliatin loss about 50% (Guo Liwei, Peng Guoping but molecular cut off is 1000 film; Pan Yang etc. " the refining comparative study that contains the Fructus Corni Chinese medicine preparation of water alcohol method and membrane separation process "; Chinese patent medicine, 1999,21 (2): 59).Wang Chengzhang etc. adopt ultrafiltrations (PS membrane, molecular cut off 30000) and polyamide absorb-elute method to the ethanol extract of Folium Ginkgo separate, purification, detect through HPLC (HPLC); The ginkgetin salidroside content is about 45%, and yield is 0.5%～0.7%, and more conventional steam distillation, organic solvent extraction method are excellent; And in ultrafiltration technology, can reduce discharge of wastewater, the protection environment reduces production costs; (Wang Chengzhang, Yu Qing, Tan Weihong etc. " application of ultrafiltration in purification Folium Ginkgo flavone glycoside " increase economic efficiency; The forestry science and technology communication, 1997, (2): 21).
Though hyperfiltration technique is applied to the production of Chinese medicine preparation its unique advantage is arranged, its degree of applying is still very limited, traces it to its cause, and remains in following problem:
(1) medicinal herb components is complicated, and particularly many compound preparations, effective ingredient are also unclear fully, therefore before hyperfiltration technique being applied to Chinese herbal and crude drugs preparations, need carry out very deep research.For example because the complexity of composition, do not carry out a large amount of pharmacology and clinical research test fully the evaluation ultrafiltration to Chinese medicine preparation in before the drug effect influence degree of each composition, can not ultrafiltration be applied to the production of most of Chinese medicine preparation.
(2) kind of membrane material is few, and membrane aperture distributes wide, and performance is understable.Used ultrafilter membrane material has cellulose acetate, polyacrylonitrile, polysulfones, SPSF, polysulfonamides etc. in Chinese medicine preparation production.By its affinity classification, be broadly divided into two types: hydrophobic film material and hydrophilic film material to water.Hydrophilic film such as cellulose acetate, SPSF material is few to solute absorption, and molecular cut off is less, but poor heat stability, mechanical strength, chemical proof property, antibacterium erosiveness are not high usually; Hydrophobic film materials such as polysulfones, mechanical strength is high, high temperature resistant, anti-solvent, anti-biodegradation, but because of containing a large amount of hydrophobicity genes or chain link in the strand, and have more electrostatic charge, thereby the permeable speed of film is low, contamination resistance is lower.
(3) pollution problem of film is to hinder hyperfiltration technique is moved towards the commercial Application stage by laboratory research biggest obstacle.In the ultra-filtration process of Chinese medicine preparation, when not good as if the medicinal liquid pretreating effect, face is prone to pollute, and fenestra stops up, and making permeation flux is that productivity ratio descends, even cisco unity malfunction, the production efficiency reduction, and cost rises, and causes shorten the service life of film.
(4) system of selection of membrane module is not set up as yet, the optimization of still needing of ultrafiltration parameter.The factor that influences the ultrafiltration effect is a lot, comprises the selection of membrane module, the cleaning method after the definite and ultrafilter of technological parameter uses etc.Therefore be applicable to ultrafiltration apparatus and the operating procedure that the ultrafiltration of Chinese medicine system is used, remain further to be studied.
The relevant practical application that utilizes ultrafiltration to prepare compound red sage root preparation, the rare report of present document, particularly, utilize ultrafiltration to carry out suitability for industrialized production is a technical barrier in this area always.The inventor is through the effort of long-term and unremitting ground; Through a large amount of experimental datas are analyzed; Verified that ultrafiltration prepares the feasibility of compound red sage root preparation, and confirmed suitable process condition, for the suitability for industrialized production of utilizing ultrafiltration to carry out compound red sage root preparation provides concrete solution.
Drop pill then has the characteristics of quick acting, relatively is fit to the need of the first aid of coronary disease with angina pectoris.Although drop pill had had very big development on production equipment, preparation technology and types of drugs in recent years, go up slower development for the research and the application of drop pill new medium adjuvant.So far, most of drop pill substrate is selected Polyethylene Glycol for use, selects polyoxyethylene monostearate, gelatin, poloxamer, polyethers etc. individually for use.From the source, Polyethylene Glycol, polyoxyethylene monostearate, poloxamer, polyethers etc. all adopt making of synthetic, though gelatin from natural, it mainly comes from skin and the bone of animal.From safety perspective,, hemolytic is in various degree arranged all though that these chemical synthetic materials such as Polyethylene Glycol, polyoxyethylene monostearate, poloxamer, polyethers all can be done is medicinal; And in the chemosynthesis process, can mix unavoidably some to the chemical constituent of toxic elements in human body side effect like oxirane, expoxy propane etc.; In addition, these synthetic materials and many medicines have incompatibility, like salicylic acid, diphenhydramine, potassium penicillin G, tetracycline etc., thereby have reduced the curative effect of these medicines.With regard to gelatin, the supplementary material of present many animal origins is carried out forbidding for avoiding zoonosis such as bovine spongiform encephalopathy, foot and mouth disease etc., and its purposes is limited.Therefore, in order to improve the product quality of drop pill, widen the application of drop pill in medical product, promote the development of drop pill dosage form, promote the internationalization of drop pill product, the drop pill new medium adjuvant of research, exploitation safety non-toxic has profound significance.But; Because dropping pill formulation technology is very strict for the requirement of substrate adjuvant; Often be difficult to prepare the drop pill that conforms to quality requirements after changing the substrate adjuvant, therefore, seek the direction that the suitable current Polyethylene Glycol of substrate adjuvant replacement becomes medical personnel effort always.
Summary of the invention
The purpose of this invention is to provide a kind of Chinese medicine composition and preparation thereof of treating cardiovascular disease.
The present invention realizes through following technical proposals:
The invention provides a kind of Chinese medicine composition of treating cardiovascular disease, it is characterized in that it is to be prepared from following materials of weight proportions medicine: Radix Salviae Miltiorrhizae 20～97, Radix Notoginseng 2～79, the Radix Astragali 10～40, Borneolum Syntheticum or Styrax 0.2～3; Be preferably: Radix Salviae Miltiorrhizae 63.0～94.0, Radix Notoginseng 4.0～35.0, the Radix Astragali 15～30, Borneolum Syntheticum or Styrax 0.5～2.0; More preferably: Radix Salviae Miltiorrhizae 75.2～90, Radix Notoginseng 9～23.5, the Radix Astragali 20～25, Borneolum Syntheticum or Styrax 0.5～1.3.
Chinese medicine composition of the present invention; Can adopt conventional method preparation; For example can Radix Salviae Miltiorrhizae, Radix Notoginseng, the Radix Astragali be mixed according to the Chinese medicine extraction method of routine or process water extract or alcohol extract separately; Then after conventional method such as concentration such as rotary evaporation, concentrating under reduced pressure are processed extractum, add Borneolum Syntheticum or Styrax and mix and promptly get.Wherein can also comprise steps such as clarification.
Impurity is few in order to obtain, the Chinese medicine composition of the little above-mentioned treatment cardiovascular disease of loss of effective components, can prepare according to the method that may further comprise the steps:
(1) Radix Salviae Miltiorrhizae, Radix Notoginseng, the Radix Astragali are mixed or process water extract or alcohol extract separately;
(2) described extracting solution being carried out predefecation handles;
(3) further described extracting solution is carried out hyperfiltration treatment;
(4) ultrafiltrate is concentrated process extractum, mix with Borneolum Syntheticum or Styrax.
In the above-mentioned steps (1), alcohol extraction can be adopted lower alcohol such as methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol of variable concentrations etc. or its mixture, preferably uses ethanol extraction.Carrying out next step predefecation after water extract or alcohol extract can not concentrate or suitably concentrate handles.
In the above-mentioned steps (2); Preliminary clarifying treatment can be carried out coarse filtration with general material such as gauze, tiffany etc.; The also available material such as the ceramic membrane of specialty carry out microfiltration; Also can behind high speed centrifugation, obtain supernatant, adsorption clarification such as also available flocculating agent such as flocculate with chitosan clarifier, 101 fruit juice clarifiers, ZTC1+1 natural clarifying agent, Ovum Gallus domesticus album flocculating agent and remove particle bigger in the medicinal liquid, also available alcohol deposition method is removed most impurity.Both can singly use above-mentioned defecation method, but also Combined application, coarse filtration-adsorption clarification for example, adsorption clarification-high speed centrifugation, coarse filtration-microfiltration, coarse filtration-precipitate with ethanol etc.After can not concentrating or suitably concentrate, the solution that predefecation is handled carries out next step ultrafiltration; Preferably do not concentrate the ultrafiltration of promptly carrying out next step.
In the above-mentioned steps (3); The used ultrafilter membrane of ultrafiltration can be cellulose diacetate film (CA), three cellulose acetate membrane (CTA), cyanoethyl cellulose film (CN-CA), PS membrane (PS), sulfonated polysulfone membrane (SPS), poly (ether sulfone) film (PES), sulfonated polyether sulfone film (SPES), polysulfonamides film (PSA), phenolphthalein side group polyarylsulfone (PAS) film (PDS), polyvinylidene fluoride film (PVDF), polyacrylonitrile film (PAN), polyimide film (N), cellulose membrane, methyl methacrylate-acrylonitrile copolymer film (MMA-AN), polyacrylonitrile/cellulose diacetate (PAN/CA) blend film; The ultrafilter membrane that dynamically forms, and the Modified Membrane of above-mentioned film.Be preferably cellulose diacetate film (CA), three cellulose acetate membrane (CTA), PS membrane (PS), sulfonated polysulfone membrane (SPS), poly (ether sulfone) film (PES), sulfonated polyether sulfone film (SPES), polysulfonamides film (PSA), polyvinylidene fluoride film (PVDF), polyacrylonitrile film (PAN).
The molecular cut off of above-mentioned ultrafilter membrane is generally 6000～80000, is preferably 10000～70000, and the best is 20000～50000.
Ultrafiltration both can be adopted cross flow filter, also can adopt dead-end filtration, but preferred cross flow filter.
The operating condition of ultrafiltration technology is following:
(1) the inlet pressure of ultrafiltration is 0.1～0.5MPa, is preferably 0.1～0.35Mpa, and the best is 0.25～0.35Mpa; The liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5～0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1～0.2Mpa.
(2) the feed liquid flow velocity is 1.0～4.0m/s, is preferably 2.0～3.0m/s.In the ultra-filtration process, adopt the fluctuation of periodicity flow so that in membrane channels, produce pulsating flow or non-stationary flow, the flow speed wave moment is 1.0～2.0m/s.
(3) feed high-pressure inert gas such as nitrogen in the ultrafiltration system discontinuous, form the gas-liquid stream of pulses, the cycle is that 0.5h～2h ventilates once, each 1 minute.
(3) feed temperature is 15～50 ℃, is preferably 20～40 ℃.
(4) when feed liquid stock solution is concentrated 1/15～1/5, add water or dilute alcohol solution ultrafiltration 1～2 time again; Be preferably when feed liquid stock solution is concentrated 1/12～1/8, add water or dilute alcohol solution ultrafiltration 1～2 time again.
(5) pH value of feed liquid is controlled at 5～9, is preferably 6.0～7.5;
(6) backwash condition: backwashing pressure is 0.15～2.5MPa, and backwashing period is that 0.5～1.5h, backwashing time are 1min～10min.When the method for alternately recoil is used in the ultrafiltration module parallel connection; Wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrating; Exchange is carried out behind the certain interval of time, generally is work 10～20min, recoil 30sec～3min.
(7) the Chemical cleaning cycle is 0.5 month～February; The Chemical cleaning medicament is generally diluted acid, diluted alkaline, surfactant; Be preferably diluted alkaline, 0.5%～4.0% sodium hydroxide for example, the mixed solution of 1.5% sodium hydroxide and 2% sodium hypochlorite etc.; PH value is 10～12, and cleaning pressure is 0.05～1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
In ultra-filtration process; Both periodic pressure oscillation or the fluctuation of periodicity flow or periodicity fed noble gas separately; Also can unite use, i.e. periodic pressure fluctuation and periodically flow fluctuation associating use, perhaps the periodic pressure fluctuation is with periodically feeding noble gas unites use; Perhaps periodically the flow fluctuation is with periodically feeding noble gas unites use, and perhaps the three unites use together.
In the technical step of the present invention (4), ultrafiltrate is condensed into extractum after, mix with Borneolum Syntheticum or Styrax get final product Chinese medicine composition of the present invention.
The present invention also provides a kind of Chinese medicinal composition preparation of treating angina pectoris, and said preparation is by above-mentioned any Chinese medicine composition and any or last made preparation of acceptable auxiliary of various medicaments.Adjuvant can be but is not limited on the pharmaceutics: starch, dextrin, lactose, microcrystalline Cellulose, hydroxypropyl methylcellulose, Polyethylene Glycol, magnesium stearate, micropowder silica gel, xylitol, lactose, glucose, glycine, mannitol, glycine etc. are mixed and made into tablet, capsule, granule, oral liquid, slow releasing preparation, controlled release preparation, gel, ointment, ointment, cream, suppository, injection, injectable powder, patch, drop pill, suspensoid, or the like.
The preferred drop pill of preparation of the present invention; This drop pill is prepared from as active component and adjuvant above-mentioned any Chinese medicine composition, perhaps is prepared from as active component and substrate adjuvant and plasticity adjuvant above-mentioned any Chinese medicine composition.
Described substrate adjuvant can be selected from drop pill substrate commonly used at present, and like Polyethylene Glycol-6000, Polyethylene Glycol-4000, Polyethylene Glycol-8000, sodium stearate, poloxamer, glyceryl monostearate etc., they can use or unite use separately.For example can select substrate Polyethylene Glycol-6000 commonly used for use, 53～58 ℃ of its condensation points.When adopting Polyethylene Glycol-6000 as substrate, its addition is 2～6 times of pharmaceutical composition of the present invention; Changing the material temperature is 60～100 ℃; The temperature of condensed fluid is 0～10 ℃ (the best is 5～10 ℃); Ball heavily is 5～50mg/ grain, diameter 1.95～4.29mm.Can or process water extract or alcohol extract separately with Radix Salviae Miltiorrhizae of the present invention, Radix Notoginseng and Radix Astragali mixing, through predefecation, after ultrafiltrate is condensed into extractum; With Borneolum Syntheticum or Styrax and adjuvant mixed evenly after; Add the transconversion into heat material, move into the jar that drips of drop pill machine, in medicine liquid droplet to condensed fluid such as liquid paraffin or the methyl-silicone oil; Remove condensed fluid, select ball.
But said substrate adjuvant is preferably from mainly from natural, the substrate adjuvant of plant origin particularly.
Specifically, the substrate adjuvant is selected from following one or more adjuvant: at least a substrate adjuvant in pharmaceutically useful monosaccharide, oligosaccharide, polysaccharide, sugar ester, sugar alcohol, fruit acid, advanced higher fatty acid derivative, high fatty alcohol, polyhydric alcohol, carbamide, the polyethylene oxide derivant.
In the above-mentioned substance, monosaccharide such as D-ribose, fructose, glucose, xylose; Oligosaccharide such as trehalose, Raffinose, maltose; Polysaccharide such as agarose; Sugar ester such as sucrose ester, D-ribonic acid-gamma lactone; Sugar alcohol such as erythritol, sorbitol, xylitol, arabitol, isomalt, lactose; Fruit acid such as malic acid, citric acid; Advanced higher fatty acid derivative such as sodium stearate, tristerin, tripalmitin, Lac; High fatty alcohol such as hexadecanol, octadecanol; Polyhydric alcohol such as phenylglycol; Polyethylene oxide derivant such as polyoxyethylene monostearate, polyoxyethylene alkyl ether, and above-claimed cpd contain water of crystallization chemical compound etc.In the above material; The natural adjuvant of plant origin such as D-ribose, fructose, glucose, xylose, trehalose, Raffinose, maltose, low melting-point agarose, sucrose ester, D-ribonic acid-gamma lactone, erythritol, sorbitol, xylitol, arabitol, isomalt, lactose, malic acid, citric acid, Lac etc., and they contain the water of crystallization chemical compound; Chemosynthesis adjuvant and animal origin adjuvant such as sodium stearate, tristerin, tripalmitin, hexadecanol, octadecanol, phenylglycol, Polyethylene Glycol, carbamide, polyoxyethylene monostearate, polyoxyethylene alkyl ether.In the above-mentioned substance, especially preferably from following one or more adjuvant: maltose, sucrose ester, sorbitol, xylitol, lactose, and they contain the water of crystallization chemical compound.
Above-mentioned substrate adjuvant is mainly the natural adjuvant of plant origin, is meant more than 50% of adjuvant of plant origin in adjuvant, and the content of chemosynthesis adjuvant and animal origin adjuvant is no more than the natural adjuvant of plant origin.Preferably; The substrate adjuvant of drop pill of the present invention only uses the natural adjuvant of plant origin, perhaps is mainly the natural adjuvant of plant origin and only contains a spot of chemosynthesis adjuvant and animal origin adjuvant, and its weight percentage is below 50%; Preferred below 40%, more preferably below 30%.The natural adjuvant of above-described so-called plant origin is meant as adjuvant itself and in plant cell or tissue, extracts, or by the material of plant extract through modifications such as derivatizations after the product of gained.So-called chemosynthesis adjuvant is meant synthetic micromolecule or the macromolecular compound that is obtained through chemical synthesis process by simple micromolecule.The natural adjuvant of so-called animal origin is meant as adjuvant itself and in the animal cell or tissue, extracts, or the material that extracts by animal through modifications such as derivatizations after the product of gained.
The substrate adjuvant of above-mentioned plant origin; Have now or in the future possibly have the synthetic article; If the synthetic article are identical or close with the character of the natural substrates adjuvant of original plant origin; Characteristic with safety non-toxic, then the natural substrates adjuvant of alternative plant origin is used as the natural substrates adjuvant that kind of above-mentioned plant origin.
For improving the formability of drop pill of the present invention, preferably also contain the plasticity adjuvant in the adjuvant of drop pill of the present invention.As this plasticity composition, for example can enumerate and be selected from following one or more composition: the natural adjuvant of plant origin such as starch and derivant, cellulose and derivant thereof, arabic gum, dextran, chitin, sesbania gum, carrageenan, Ficus elastica, Furcellaran, tragakanta, carrageenin, tamarind gum, pectin, xanthan gum, alginic acid and salt thereof, dextrin, cyclodextrin, agar, lactose; Chemosynthesis adjuvant and animal origin adjuvant such as polyvinylpyrrolidone, crospolyvinylpyrrolidone, carbomer, polyvinyl alcohol, acrylic resin, poloxamer, silicon dioxide, gelatin etc.
Above-mentioned starch and derivant thereof such as pregelatinized Starch, modified starch, hydroxypropyl starch, carboxymethyl starch etc.Said cellulose and derivant thereof such as methylcellulose, microcrystalline Cellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, cross-linking sodium carboxymethyl cellulose, hydroxyethylmethyl-cellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose.
In the plasticity composition, preferably from following one or more adjuvant: pregelatinized Starch, carboxymethyl starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, arabic gum, alginic acid, dextrin, cyclodextrin, agar, lactose.In addition, glyceryl monostearate, polyoxyethylene monostearate also can be used as the plasticity composition and other substrate supplementary product compatibility is used.
The composition of above-described so-called plant origin is meant as adjuvant itself and in plant cell or tissue, extracts, or by the material of plant extract through modifications such as derivatizations after the product of gained.So-called chemosynthesis adjuvant is meant synthetic micromolecule or the macromolecular compound that is obtained through chemical synthesis process by simple micromolecule.The adjuvant of so-called animal origin is meant as adjuvant itself and in the animal cell or tissue, extracts, or the material that extracts by animal through modifications such as derivatizations after the product of gained.
The plasticity composition of above-mentioned plant origin; Have now or in the future possibly have the synthetic article; If the synthetic article are identical or close with the character of the natural plasticity composition of plant origin; Characteristic with safety non-toxic, then the natural plasticity composition of alternative above-mentioned plant origin is used as the natural plasticity substrate adjuvant that kind of above-mentioned plant origin.
The substrate adjuvant in the above-mentioned substrate adjuvant that is selected from monosaccharide, oligosaccharide, polysaccharide, sugar ester, sugar alcohol, fruit acid, advanced higher fatty acid derivative, high fatty alcohol, polyhydric alcohol, carbamide, polyethylene oxide derivant etc., preferred plant source is selected to arrange in pairs or groups according to medicinal property with above-mentioned plasticity composition; It is preferably arranged in pairs or groups and is xylitol and starch, lactose and starch, xylitol and arabic gum, sucrose ester and glyceryl monostearate, sucrose ester and polyoxyethylene monostearate, sucrose ester and polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose, sucrose ester and polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose and silicon dioxide etc., but is not limited thereto.
Above-mentioned drop pill substrate adjuvant is 1: 0.1～1 with the ratio of the weight of pharmaceutical composition, be preferably 1: 0.1～and 0.6, the best is 1: 0.2～0.4.
The weight ratio of above-mentioned substrate adjuvant and plasticity composition is 1: 0～1.5, be preferably 1: 0.1～and 0.9, the best is 1: 0.1～0.5.
In the above-mentioned substrate adjuvant, xylitol is preferably 1: 0.2 with the ratio of the weight of starch～and 0.3;
In the above-mentioned substrate adjuvant, lactose is preferably 1: 0.2 with the ratio of the weight of starch～and 0.3;
In the above-mentioned substrate adjuvant, the ratio of the weight of xylitol and arabic gum is preferably 1: 0.2～and 0.4;
In the above-mentioned substrate adjuvant, the weight ratio of sucrose ester and glyceryl monostearate is 1: 0.1～1, and the best is 1: 0.5.
In the above-mentioned substrate adjuvant, the weight ratio of sucrose ester and polyoxyethylene monostearate is 1: 0.1～1, and the best is 1: 0.5.
In the above-mentioned substrate adjuvant, the weight ratio of sucrose ester and polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose is 1: (0.1～1): (0.1～1), the best are 1: 0.4: 0.6.
In the above-mentioned substrate adjuvant, the weight ratio of sucrose ester and polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose and silicon dioxide is 15: (7～15): (0.1～2): (0.1～2), the best are 15: 11: 1: 1.
Dropping pill formulation of the present invention adopts one or more aforesaid substrate adjuvants, and the substrate adjuvant meets aforementioned requirement with the ratio of the weight of medicine, and the substrate adjuvant also meets aforementioned requirement with the ratio of the weight of plasticity composition.The preparation of drop pill can be adopted following process conditions: medicine mixes mixing time with the substrate adjuvant be 10～30 minutes; A mixed heating and melting temperature of medicine and substrate adjuvant or a system temperature are 45～95 ℃, are preferably 60～95 ℃; Liquid coolant is liquid paraffin, methyl-silicone oil or vegetable oil such as Oleum Glycines, Semen Ricini wet goods, is preferably liquid paraffin, methyl-silicone oil; The temperature of liquid coolant is-20～30 ℃, is preferably 0～18 ℃; Dropper mouth internal diameter is 1.0～4.0mm, is preferably 1.2～2.5mm; The difference of dropper mouth external diameter and internal diameter is less for well.
Through medicine of the present invention its beneficial effect is explained in the experiment of the protective effect of Ischemia and Reperfusion in vivo in Rats myocardial damage below.
1. animal model: Wistar strain male rat, open chest anesthetized is kept breathing, between left auricle and pulmonary conus, around left coronary artery, and carries out ligation.
2. method: rat is divided into 4 groups at random: 1. sham operated rats (sham-operated control), normal saline is irritated stomach, 1ml/ days, totally 4 days; 2. myocardial ischemia-reperfusion group (M-IR), it is the same to irritate the stomach method; 3. FUFANG DANSHEN PIAN group (with reference to the preparation of the method for 2000 editions FUFANG DANSHEN PIANs of Chinese Pharmacopoeia) was dissolved in the 1ml normal saline with 2g crude drug/kg/ days, and it is the same to irritate the stomach method; 4. drug group of the present invention (press embodiment six method preparation and extractum), be dissolved in the 1ml normal saline with 2g crude drug/kg/ days, it is the same to irritate the stomach method.
Not ligation of sham operated rats; Other group is in ligation perfusion again after 1 hour.Take out after injecting 1% her Wen orchid in the ligation left coronary artery once more before sacrifice of animal, ventricle, with the PBS rinsing, freezing 1 hour.After removing unnecessary tissue, 30 minutes (37 ℃) of dyeing in 1%TTC.With weight method calculating myocardium ischemia hazardous area (she does not dye the district by the Wen orchid), infarcted region (TTC does not dye the district).
3. the result of variations of myocardial infarct size
The myocardial infarction phenomenon was not seen in sham-operation in 7 hours; It is obvious that myocardial ischemia poured into after 6 hours myocardial infarction in 1 hour again; Medicine of the present invention can obviously dwindle the myocardial infarct size of myocardial reperfusion rat, shows that medicine of the present invention pours into the variation of myocardium cell necrosis property again to ischemic myocardial cells good protective action (seeing table 1) is arranged.
Table 1 is respectively organized the variation of myocardial infarct size
Annotate: compare with the M-IR group,
*P＜0.05,
*P＜0.01; Compare with the FUFANG DANSHEN PIAN group,
△P＜0.05,
△ △P＜0.01.
The specific embodiment
Below in conjunction with embodiment the present invention is done further elaboration.These embodiment only are used to the purpose of giving an example, rather than limit the present invention by any way.
Embodiment one
Crude drug adopts Radix Salviae Miltiorrhizae 375g, Radix Notoginseng 118g, Borneolum Syntheticum 8g, Radix Astragali 100g.
Obtain the ethanol extract of the Radix Salviae Miltiorrhizae and the Radix Astragali with the ethanol extraction Radix Salviae Miltiorrhizae and the Radix Astragali, with extracting liquid filtering, collect filtrating with gauze.It is that 6000 cellulose diacetate film carries out ultrafiltration that filtrating is used molecular cut off, and filter type adopts cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 5.Backwashing pressure is 0.15MPa, and backwashing period is that 0.5h, backwashing time are 1min.When the method for alternately recoil was used in ultrafiltration module parallel connection, wherein a cover or a few cover carried out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of part filtrating, and exchange is carried out behind the certain interval of time, work 10min, recoil 30sec.The Chemical cleaning cycle is 0.5 month, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 0.05MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35～1.39 (55 ℃).Radix Notoginseng powder is broken into fine powder, mixes all with above-mentioned extractum, drying is processed granule.With the Borneolum Syntheticum porphyrize, be mixed with above-mentioned granule, be pressed into 1000, or sugar coating, promptly get.
Embodiment two
Crude drug adopts Radix Salviae Miltiorrhizae 465g, Radix Notoginseng 30g, Styrax 8g, Radix Astragali 85g.
Obtain the ethanol extract of the Radix Salviae Miltiorrhizae and the Radix Astragali with the ethanol extraction Radix Salviae Miltiorrhizae and the Radix Astragali, carry out microfiltration, collect filtrating with ceramic membrane.It is that 80000 PS membrane carries out ultrafiltration that filtrating is used molecular cut off, and filter type adopts dead-end filtration.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When the method for alternately recoil was used in ultrafiltration module parallel connection, wherein a cover or a few cover carried out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of part filtrating, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35～1.39 (55 ℃).Radix Notoginseng powder is broken into fine powder, mixes all,, be mixed, add 3% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules with above-mentioned granule with the Styrax porphyrize with above-mentioned extractum, 60 ℃ of dryings 30～45 minutes, granulate, the adding Pulvis Talci, mixing fills in capsule, promptly gets.
Embodiment three
Crude drug adopts Radix Salviae Miltiorrhizae 490g, Radix Notoginseng 84g, Borneolum Syntheticum 6g, Radix Astragali 60g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization are added in the extraction pot, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, merging filtrate.It is that 6000 three cellulose acetate membrane carries out ultrafiltration that filtrating is used molecular cut off, and filter type adopts cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 5.Backwashing pressure is 0.15MPa, and backwashing period is that 0.5h, backwashing time are 1min.When the method for alternately recoil was used in ultrafiltration module parallel connection, wherein a cover or a few cover carried out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of part filtrating, and exchange is carried out behind the certain interval of time, work 10min, recoil 30sec.The Chemical cleaning cycle is 0.5 month, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 0.05MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.32～1.40 (55 ℃), add Borneolum Syntheticum, mix homogeneously, with the lactose fluidisation, drying is processed granule, promptly gets in the batch (-type) fluid bed.
Embodiment four
Crude drug adopts Radix Salviae Miltiorrhizae 242g, Radix Notoginseng 255g, Styrax 4g, Radix Astragali 100g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization are added in the extraction pot, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, merging filtrate.It is that 60000 PS membrane carries out ultrafiltration that filtrating is used molecular cut off, and filter type adopts dead-end filtration.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When the method for alternately recoil was used in ultrafiltration module parallel connection, wherein a cover or a few cover carried out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of part filtrating, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.32～1.40 (55 ℃), add Styrax, again with mannitol 30g, calcium disodium edetate 5g, distilled water 5ml, behind the said components mixing, lyophilization, packing promptly gets.
Embodiment five
Crude drug adopts Radix Salviae Miltiorrhizae 24.2g, Radix Notoginseng 25.5g, Styrax 0.4g, Radix Astragali 10.0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization are added in the extraction pot, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill filtration.It is that 50000 PS membrane carries out ultrafiltration that filtrating is used molecular cut off, and filter type adopts dead-end filtration.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When the method for alternately recoil was used in ultrafiltration module parallel connection, wherein a cover or a few cover carried out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of part filtrating, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.32～1.40 (55 ℃); Get extractum and Styrax, evenly mixed with Polyethylene Glycol-6000 20g, be heated to 60 ℃ of temperature; Change material after 20～120 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In ℃ liquid paraffin of medicine liquid droplet to 7～8, take out drop pill, oil removing, screen cloth selects ball, processes 1000 drop pill, promptly gets.
Embodiment six
Crude drug Radix Salviae Miltiorrhizae 24.2g, Radix Notoginseng 25.5g, Borneolum Syntheticum 0.4g, Radix Astragali 10.0g; Adjuvant lactose 18.0g, pregelatinized Starch 4.5g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill, and filters, and filtrating is concentrated to obtain the extractum that relative density is 1.32～1.40 (55 ℃).
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant lactose and pregelatinized Starch, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.
The drop pill (newly) that the new substrate adjuvant of above-mentioned usefulness is processed compares (seeing the following form) with dissolve scattered time limit, the weight differential of using polyethylene glycol 6000 to process drop pill (old, embodiment five) as adjuvant
Above test data shows, the Chinese medicine dripping pills of processing with new substrate adjuvant of the present invention to dissolve the speed of loosing faster, be more conducive to medicine and play a role in the shortest time; The ball method of double differences is different all to be controlled in the pharmacopeia prescribed limit, and the alternative present chemosynthesis adjuvant of this natural substrates adjuvant is described, carries out suitability for industrialized production.
Embodiment seven
Crude drug Radix Salviae Miltiorrhizae 16.2g, Radix Notoginseng 29.5g, Borneolum Syntheticum 0.4g, Radix Astragali 13.8g; Adjuvant xylitol 15.0g, starch 5.0g.
Learn from else's experience Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, add the 0.9g sodium bicarbonate, add 4 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, adds 4 times of water gagings, decocted 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 75%, leaves standstill, and filters, and filtrating is concentrated to obtain the extractum that relative density is 1.32～1.40 (55 ℃).
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant xylitol and starch, be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 8 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.81min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment eight
Crude drug Radix Salviae Miltiorrhizae 30.8g, Radix Notoginseng 5.0g, Borneolum Syntheticum 0.8g, Radix Astragali 21.5g; Adjuvant lactose 15.0g, arabic gum 3.0g.
With ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng and the Radix Astragali, obtain the ethanol extract of Radix Salviae Miltiorrhizae, Radix Notoginseng and the Radix Astragali, with this extracting liquid filtering, collect filtrating with gauze.It is that 20000 cellulose diacetate film carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The condition of above-mentioned ultrafiltration is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant lactose and arabic gum, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 6 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.63min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment nine
Crude drug Radix Salviae Miltiorrhizae 46.5g, Radix Notoginseng 3.0g, Borneolum Syntheticum 0.8g, Radix Astragali 8.5g; Adjuvant xylitol 16.0g, tragakanta 5.0g.
The Radix Salviae Miltiorrhizae and the Radix Notoginseng of coarse pulverization are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, and merging filtrate gets Radix Salviae Miltiorrhizae and Radix Notoginseng extracting solution.With the 70% ethanol extraction Radix Astragali, get Radix Astragali extractive solution.With above-mentioned Radix Salviae Miltiorrhizae and Radix Notoginseng extracting solution and Radix Astragali extractive solution merging, leave standstill, filter.It is that 60000 PS membrane carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant xylitol and tragakanta, be heated to 60 ℃ of temperature, change material after 25 minutes, move in the dropping-pill machine jar that jar temperature remains on 89 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.64min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment ten
Crude drug Radix Salviae Miltiorrhizae 26.0g, Radix Notoginseng 16.5g, Borneolum Syntheticum 0.7g, Radix Astragali 17.0g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 8.0g.
With 80% ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng and the Radix Astragali, obtain the ethanol extract of Radix Salviae Miltiorrhizae, Radix Notoginseng and the Radix Astragali, with obtaining supernatant behind this extracting solution high speed centrifugation.It is that 50000 sulfonated polysulfone membrane carries out ultrafiltration that this liquid is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant sucrose ester and polyoxyethylene monostearate, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.69min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 11
Crude drug Radix Salviae Miltiorrhizae 49.0g, Radix Notoginseng 8.4g, Borneolum Syntheticum 0.6g, Radix Astragali 6.0g; Adjuvant sucrose ester 15.0g, glyceryl monostearate 4.0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.It is that 60000 poly (ether sulfone) film carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant sucrose ester and glyceryl monostearate, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 6 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.72min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 12
Crude drug Radix Salviae Miltiorrhizae 21.0g, Radix Notoginseng 16.6g, Borneolum Syntheticum 0.6g, Radix Astragali 23.5g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 2.0g, cross-linking sodium carboxymethyl cellulose 3.0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.It is that 60000 PS membrane carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 5.
Get above-mentioned extractum and Borneolum Syntheticum, evenly be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with adjuvant sucrose ester, polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose are mixed.In medicine liquid droplet to the 4 ℃ methyl-silicone oil, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.67min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 13
Crude drug Radix Salviae Miltiorrhizae 31.0g, Radix Notoginseng 18.0g, Borneolum Syntheticum 0.4g, Radix Astragali 12.5g; Adjuvant lactose 10.0g, carrageenan 8.0g, starch 2.0g.
Learn from else's experience Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, add the 0.89g sodium bicarbonate, add 4 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, adds 4 times of water gagings, decocted 1 hour, and filtration, filtering residue discards, merging filtrate.It is that 50000 polysulfonamides film carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.
Get above-mentioned extractum and Borneolum Syntheticum, evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with adjuvant lactose, carrageenan and starch are mixed.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.83min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 14
Crude drug Radix Salviae Miltiorrhizae 28.0g, Radix Notoginseng 7.8g, Borneolum Syntheticum 0.6g, Radix Astragali 25.6g; Adjuvant xylitol 10.0g, lactose 3.0g, arabic gum 5.0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 75%, leaves standstill filtration.It is that 20000 PS membrane carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 6.
Get above-mentioned extractum and Borneolum Syntheticum, evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 84 ℃ with adjuvant xylitol, lactose and arabic gum are mixed.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.59min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 15
Crude drug Radix Salviae Miltiorrhizae 18.0g, Radix Notoginseng 25.0g, Borneolum Syntheticum 0.6g, Radix Astragali 18.7g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 6.0g, cross-linking sodium carboxymethyl cellulose 1.0g, silica 1 .0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill filtration.It is that 20000 PS membrane carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 6.
Get above-mentioned extractum and Borneolum Syntheticum,, mixed evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 84 ℃ with adjuvant sucrose ester, polyoxyethylene monostearate, cross-linking sodium carboxymethyl cellulose and silicon dioxide.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.56min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 16
Crude drug Radix Salviae Miltiorrhizae 23.0g, Radix Notoginseng 12.0g, Borneolum Syntheticum 0.4g, Radix Astragali 27.0g; Adjuvant lactose 14.0g, tragakanta 5.0g.
Learn from else's experience Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, add the 0.88g sodium bicarbonate, add 4 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, adds 4 times of water gagings, decocted 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill filtration.It is that 20000 polyvinylidene fluoride film carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/9, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant lactose and tragakanta, be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 8 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.48min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 17
Crude drug Radix Salviae Miltiorrhizae 24.2g, Radix Notoginseng 25.5g, Styrax 0.4g, Radix Astragali 10.0g; Adjuvant lactose 18.0g, pregelatinized Starch 4.5g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill, and filters, and filtrating is concentrated to obtain the extractum that relative density is 1.32～1.40 (55 ℃).
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant lactose and pregelatinized Starch, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.86min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 18
Crude drug Radix Salviae Miltiorrhizae 16.2g, Radix Notoginseng 29.5g, Styrax 0.4g, Radix Astragali 13.8g; Adjuvant xylitol 15.0g, starch 5.0g.
Learn from else's experience Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, add the 0.9g sodium bicarbonate, add 4 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, adds 4 times of water gagings, decocted 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 75%, leaves standstill, and filters, and filtrating is concentrated to obtain the extractum that relative density is 1.32～1.40 (55 ℃).
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant xylitol and starch, be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 8 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.82min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 19
Crude drug Radix Salviae Miltiorrhizae 30.8g, Radix Notoginseng 5.0g, Styrax 0.8g, Radix Astragali 21.5g; Adjuvant lactose 15.0g, arabic gum 3.0g.
With ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng and the Radix Astragali, obtain the ethanol extract of Radix Salviae Miltiorrhizae, Radix Notoginseng and the Radix Astragali, with this extracting liquid filtering, collect filtrating with gauze.It is that 20000 cellulose diacetate film carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The condition of above-mentioned ultrafiltration is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant lactose and arabic gum, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 6 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.65min of baffle plate through screen cloth, meets the pharmacopeia regulation disintegration.
Embodiment 20
Crude drug Radix Salviae Miltiorrhizae 46.5g, Radix Notoginseng 3.0g, Styrax 0.8g, Radix Astragali 8.5g; Adjuvant xylitol 16.0g, tragakanta 5.0g.
The Radix Salviae Miltiorrhizae and the Radix Notoginseng of coarse pulverization are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, and merging filtrate gets Radix Salviae Miltiorrhizae and Radix Notoginseng extracting solution.With the 70% ethanol extraction Radix Astragali, get Radix Astragali extractive solution.With above-mentioned Radix Salviae Miltiorrhizae and Radix Notoginseng extracting solution and Radix Astragali extractive solution merging, leave standstill, filter.It is that 60000 PS membrane carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant xylitol and tragakanta, be heated to 60 ℃ of temperature, change material after 25 minutes, move in the dropping-pill machine jar that jar temperature remains on 89 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.68min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 21
Crude drug Radix Salviae Miltiorrhizae 26.0g, Radix Notoginseng 16.5g, Styrax 0.7g, Radix Astragali 17.0g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 8.0g.
With 80% ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng and the Radix Astragali, obtain the ethanol extract of Radix Salviae Miltiorrhizae, Radix Notoginseng and the Radix Astragali, with obtaining supernatant behind this extracting solution high speed centrifugation.It is that 50000 sulfonated polysulfone membrane carries out ultrafiltration that this liquid is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant sucrose ester and polyoxyethylene monostearate, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.73mi n of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 22
Crude drug Radix Salviae Miltiorrhizae 49.0g, Radix Notoginseng 8.4g, Styrax 0.6g, Radix Astragali 6.0g; Adjuvant sucrose ester 15.0g, glyceryl monostearate 4.0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.It is that 60000 poly (ether sulfone) film carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant sucrose ester and glyceryl monostearate, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 6 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.75min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 23
Crude drug Radix Salviae Miltiorrhizae 21.0g, Radix Notoginseng 16.6g, Styrax 0.6g, Radix Astragali 23.5g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 2.0g, cross-linking sodium carboxymethyl cellulose 3.0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.It is that 60000 PS membrane carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 5.
Get above-mentioned extractum and Styrax, evenly be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with adjuvant sucrose ester, polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose are mixed.In medicine liquid droplet to the 4 ℃ methyl-silicone oil, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.67min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 24
Crude drug Radix Salviae Miltiorrhizae 31.0g, Radix Notoginseng 18.0g, Styrax 0.4g, Radix Astragali 12.5g; Adjuvant lactose 10.0g, carrageenan 8.0g, starch 2.0g.
Learn from else's experience Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, add the 0.89g sodium bicarbonate, add 4 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, adds 4 times of water gagings, decocted 1 hour, and filtration, filtering residue discards, merging filtrate.It is that 50000 polysulfonamides film carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.
Get above-mentioned extractum and Styrax, evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with adjuvant lactose, carrageenan and starch are mixed.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.83min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 25
Crude drug Radix Salviae Miltiorrhizae 28.0g, Radix Notoginseng 7.8g, Styrax 0.6g, Radix Astragali 25.6g; Adjuvant xylitol 10.0g, lactose 3.0g, arabic gum 5.0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 75%, leaves standstill filtration.It is that 20000 PS membrane carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 6.
Get above-mentioned extractum and Styrax, evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 84 ℃ with adjuvant xylitol, lactose and arabic gum are mixed.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.55min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 26
Crude drug Radix Salviae Miltiorrhizae 18.0g, Radix Notoginseng 25.0g, Styrax 0.6g, Radix Astragali 18.7g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 6.0g, cross-linking sodium carboxymethyl cellulose 1.0g, silica 1 .0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill filtration.It is that 20000 PS membrane carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 6.
Get above-mentioned extractum and Styrax,, mixed evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 84 ℃ with adjuvant sucrose ester, polyoxyethylene monostearate, cross-linking sodium carboxymethyl cellulose and silicon dioxide.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.57min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 27
Crude drug Radix Salviae Miltiorrhizae 23.0g, Radix Notoginseng 12.0g, Styrax 0.4g, Radix Astragali 27.0g; Adjuvant lactose 14.0g, tragakanta 5.0g.
Learn from else's experience Radix Salviae Miltiorrhizae, Radix Notoginseng and the Milkvetch Root of coarse pulverization to extraction pot, add the 0.88g sodium bicarbonate, add 4 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, adds 4 times of water gagings, decocted 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill filtration.It is that 20000 polyvinylidene fluoride film carries out ultrafiltration that filtrating is used molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow; The flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses; Cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/9, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant lactose and tragakanta, be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 8 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly gets.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.52min of baffle plate through screen cloth, meets the pharmacopeia regulation this disintegration.
Claims (10)
1. Chinese medicine composition of treating myocardial ischemia-reperfusion injury is characterized in that it is to be prepared from following materials of weight proportions medicine:
Radix Salviae Miltiorrhizae 20～97
Radix Notoginseng 2～79
The Radix Astragali 10～40
Styrax 0.2～3.
2. Chinese medicine composition as claimed in claim 1 is characterized in that the weight proportion of described crude drug is:
Radix Salviae Miltiorrhizae 63.0～94
Radix Notoginseng 4.0～35
The Radix Astragali 15～30
Styrax 0.5～2.0.
3. Chinese medicine composition as claimed in claim 2 is characterized in that the weight proportion of described crude drug is:
Radix Salviae Miltiorrhizae 75.2～90
Radix Notoginseng 9～23.5
The Radix Astragali 20～25
Styrax 0.5～1.3.
4. like the described arbitrary Chinese medicine composition of claim 1～3, it is characterized in that its preparation comprises the steps:
(a) Radix Salviae Miltiorrhizae, Radix Notoginseng, the Radix Astragali are mixed or process water extract or alcohol extract separately;
(b) described extracting solution being carried out predefecation handles;
(c) further described extracting solution is carried out hyperfiltration treatment;
(d) ultrafiltrate is concentrated process extractum, mix with Styrax.
5. Chinese medicine composition as claimed in claim 4 is characterized in that the alcohol extraction employing of said step a is selected from following lower alcohol or its mixture: methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol; And/or
Described predefecation is treated to coarse filtration-adsorption clarification, adsorption clarification-high speed centrifugation, coarse filtration-microfiltration or coarse filtration-precipitate with ethanol; And/or
The used ultrafilter membrane of said hyperfiltration treatment is selected from: cellulose diacetate film, three cellulose acetate membrane, cyanoethyl cellulose film, PS membrane, sulfonated polysulfone membrane, poly (ether sulfone) film, sulfonated polyether sulfone film, polysulfonamides film, phenolphthalein side group polyarylsulfone (PAS) film, polyvinylidene fluoride film, polyacrylonitrile film, polyimide film, cellulose membrane, methyl methacrylate-acrylonitrile copolymer film, polyacrylonitrile/cellulose diacetate blend film; The ultrafilter membrane that dynamically forms, and the Modified Membrane of above-mentioned film; The molecular cut off of its ultrafilter membrane is 6000～80000; And/or
The operating procedure condition of said hyperfiltration treatment is following: the inlet pressure of ultrafiltration is 0.1～0.5MPa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25～0.5kPa; Feed temperature is 15～50 ℃; The pH value of feed liquid is controlled at 5～9;
When feed liquid stock solution is concentrated 1/15～1/5, add water or dilute alcohol solution ultrafiltration 1～2 time again; And/or
The independent following method that adopts of perhaps uniting in the process of said ultrafiltration: periodic pressure fluctuation, periodicity flow fluctuate, feed off and on noble gas; Wherein the pressure wave moment of periodic pressure fluctuation is 0.1～0.2Mpa, and periodically the flow speed wave moment of flow fluctuation is 1.0～2.0 meter per seconds, feeds noble gas off and on and be ventilation in 0.5 hour～2 hours once, each 1 minute.
6. Chinese medicinal composition preparation of treating myocardial ischemia-reperfusion injury, said preparation is gone up acceptable auxiliary by any Chinese medicine composition of claim 1-5 and any or various medicaments and is processed.
7. preparation as claimed in claim 6; Said preparation is a drop pill; Described drop pill; Any Chinese medicine composition and substrate adjuvant claim 1-5 are prepared from; Perhaps be prepared from any Chinese medicine composition of claim 1-5 and substrate adjuvant and plasticity adjuvant, wherein said substrate adjuvant is selected from least a in pharmaceutically useful monosaccharide, oligosaccharide, polysaccharide, sugar ester, sugar alcohol, fruit acid, advanced higher fatty acid derivative, high fatty alcohol, polyhydric alcohol, carbamide, the polyethylene oxide derivant; Said plasticity substrate adjuvant is selected from starch and derivant, arabic gum, dextran, chitin, sesbania gum, carrageenan, Ficus elastica, Furcellaran, tragakanta, carrageenin, tamarind gum, pectin, xanthan gum, alginic acid and salt thereof, dextrin, cyclodextrin, agar, lactose; Polyvinylpyrrolidone, crospolyvinylpyrrolidone, carbomer, polyvinyl alcohol, acrylic resin, poloxamer, silicon dioxide, gelatin, glyceryl monostearate, polyoxyethylene monostearate.
8. preparation according to claim 7 is characterized in that, said substrate adjuvant is selected from sorbitol, xylitol, lactose, maltose, sucrose ester, and they contain in the water of crystallization chemical compound one or more; Said plasticity substrate adjuvant is selected from one or more in pregelatinized Starch, carboxymethyl starch, arabic gum, alginic acid, agar, lactose, glyceryl monostearate, polyoxyethylene monostearate, cross-linking sodium carboxymethyl cellulose, the silicon dioxide.
9. preparation according to claim 8; Wherein said adjuvant is selected from a kind of of combinations: lactose and starch; Xylitol and arabic gum, sucrose ester and glyceryl monostearate, sucrose ester and polyoxyethylene monostearate; Sucrose ester, polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose, or sucrose ester, polyoxyethylene monostearate, cross-linking sodium carboxymethyl cellulose and silicon dioxide.
10. preparation as claimed in claim 9 is characterized in that the wherein said substrate adjuvant and the ratio of the weight of medicine are 1: 0.1～1; And/or the weight ratio of described substrate adjuvant and plasticity composition is 1: 0～1.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006100142629A CN101085018B (en) | 2006-06-08 | 2006-06-08 | Traditional Chinese medicinal composition containing red sage root, notoginseng, radix astragali and borneol or storax and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006100142629A CN101085018B (en) | 2006-06-08 | 2006-06-08 | Traditional Chinese medicinal composition containing red sage root, notoginseng, radix astragali and borneol or storax and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101085018A CN101085018A (en) | 2007-12-12 |
| CN101085018B true CN101085018B (en) | 2012-01-04 |
Family
ID=38936302
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2006100142629A Active CN101085018B (en) | 2006-06-08 | 2006-06-08 | Traditional Chinese medicinal composition containing red sage root, notoginseng, radix astragali and borneol or storax and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101085018B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3777866A4 (en) | 2018-04-04 | 2022-01-05 | Tasly Pharmaceutical Group Co., Ltd. | Pharmaceutical composition and application thereof |
| JP2023525627A (en) * | 2020-04-29 | 2023-06-19 | タスリー・ファーマシューティカル・グループ・カンパニー・リミテッド | Use of a Chinese herbal composition and its formulation in the manufacture of a medicine for the prevention and/or treatment of novel coronavirus pneumonia |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1087272A (en) * | 1992-11-28 | 1994-06-01 | 河南省中药研究所 | A kind of Chinese powder medicine capsule that is used for the treatment of chronic ischemic heart disease |
| CN1778340A (en) * | 2004-11-26 | 2006-05-31 | 天津天士力制药股份有限公司 | Chinese medicine composition for treating coronary heart disease and angina cordis |
-
2006
- 2006-06-08 CN CN2006100142629A patent/CN101085018B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1087272A (en) * | 1992-11-28 | 1994-06-01 | 河南省中药研究所 | A kind of Chinese powder medicine capsule that is used for the treatment of chronic ischemic heart disease |
| CN1778340A (en) * | 2004-11-26 | 2006-05-31 | 天津天士力制药股份有限公司 | Chinese medicine composition for treating coronary heart disease and angina cordis |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101085018A (en) | 2007-12-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101085071B (en) | Traditional Chinese medicinal composition containing red sage root and haw and its preparation | |
| CN101085012B (en) | Composition containing safflower for treating cardiovascular diseases and its preparation | |
| CN101085004B (en) | Traditional Chinese medicinal composition containing red sage root, ligusticum wallichii and borneol or storax and its preparation | |
| CN101085064B (en) | Composition containing radix paeoniae rubrathe for treating cardiovascular diseases and its preparation | |
| CN101085013B (en) | Traditional Chinese medicinal composition containing red sage root, safflower, radix astragali and dalbergia oil and its preparation | |
| CN101085018B (en) | Traditional Chinese medicinal composition containing red sage root, notoginseng, radix astragali and borneol or storax and its preparation | |
| CN101085134A (en) | Composition containing dragon blood for treating cardiovascular diseases and preparation | |
| CN101085005B (en) | Traditional Chinese medicinal composition containing red sage root, ligusticum wallichii and dalbergia oil and its preparation | |
| CN101085003A (en) | Traditional Chinese medicinal composition containing red sage root, radix paeoniae rubrathe and borneol or storax and its preparation | |
| CN101085016B (en) | Traditional Chinese medicinal composition containing red sage root, notoginseng and ginseng or codonopsis pilosula and its preparation | |
| CN101085014B (en) | Traditional Chinese medicinal composition containing red sage root, notoginseng, safflower and borneol or storax and its preparation | |
| CN101085015B (en) | Traditional Chinese medicinal composition containing red sage root, notoginseng, safflower and dalbergia oil and its preparation | |
| CN101084957A (en) | Composition containing notoginseng and rhus taishanensis for treating cardiovascular diseases and preparation thereof | |
| CN101085056B (en) | Traditional Chinese medicinal composition containing red sage root, radix paeoniae rubrathe and dalbergia oil and its preparation | |
| CN101084959B (en) | Traditional Chinese medicinal composition containing ligusticum wallichii, notoginseng and borneol or storax and preparation thereof | |
| CN101088522B (en) | Chinese medicine composition containing red sage, notoginseng and musk or muskone and its prepn | |
| CN101084993B (en) | Medicinal composition containing dalbergia and storax, preparation method and preparation | |
| CN101085019B (en) | Traditional Chinese medicinal composition containing red sage root, notoginseng, safflower and musk or muscone and its preparation | |
| CN101085021B (en) | Medicinal composition containing safflower and radix astragali, preparation method and preparation | |
| CN101084950B (en) | Traditional Chinese medicinal composition containing red sage root, notoginseng, radix astragali and musk or muscone and preparation | |
| CN101085026B (en) | Medicinal composition containing red sage root and musk, preparation method and preparation | |
| CN101085025A (en) | Medicinal composition containing red sage root and safflower, preparation method and preparation | |
| CN101085017A (en) | Traditional Chinese medicinal composition containing red sage root and safflower and its preparation | |
| CN101084956A (en) | Traditional Chinese medicinal composition containing ligusticum wallichii, notoginseng and dalbergia oil and preparation thereof | |
| CN101084994B (en) | Medicinal composition containing red sage root and ginseng, preparation method and preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: TASLY PHARMACEUTICAL GROUP CO., LTD. Free format text: FORMER NAME: TIANJIN TASLY PHARMACEUTICAL CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 300402 Tianjin Beichen Xinyi white road Liaohe Road No. 1 Patentee after: Tasly Pharmaceutical Group Co., Ltd. Address before: 300402 Tianjin Beichen Xinyi white road Liaohe Road No. 1 Patentee before: Tianjin Tianshili Pharmaceutical Co., Ltd. |
|
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 300402 Tianjin Beichen Xinyi white road Liaohe Road No. 1 Patentee after: Tasly Pharmaceutical Group Limited by Share Ltd Address before: 300402 Tianjin Beichen Xinyi white road Liaohe Road No. 1 Patentee before: Tasly Pharmaceutical Group Co., Ltd. |