WO2014015507A1 - Application of shengui capsule in preparing antithrombotic drugs - Google Patents
Application of shengui capsule in preparing antithrombotic drugs Download PDFInfo
- Publication number
- WO2014015507A1 WO2014015507A1 PCT/CN2012/079235 CN2012079235W WO2014015507A1 WO 2014015507 A1 WO2014015507 A1 WO 2014015507A1 CN 2012079235 W CN2012079235 W CN 2012079235W WO 2014015507 A1 WO2014015507 A1 WO 2014015507A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- red ginseng
- application
- chuanxiong
- application according
- capsule
- Prior art date
Links
- 239000002775 capsule Substances 0.000 title claims abstract description 45
- 229940127217 antithrombotic drug Drugs 0.000 title claims abstract description 6
- 235000002789 Panax ginseng Nutrition 0.000 claims abstract description 54
- 244000037364 Cinnamomum aromaticum Species 0.000 claims abstract description 9
- 235000014489 Cinnamomum aromaticum Nutrition 0.000 claims abstract description 9
- 229940126680 traditional chinese medicines Drugs 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 58
- 239000003814 drug Substances 0.000 claims description 40
- 239000000843 powder Substances 0.000 claims description 39
- 238000002360 preparation method Methods 0.000 claims description 37
- 208000007536 Thrombosis Diseases 0.000 claims description 23
- 239000000706 filtrate Substances 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 18
- 239000000341 volatile oil Substances 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 9
- 239000012141 concentrate Substances 0.000 claims description 8
- 229920002472 Starch Polymers 0.000 claims description 7
- 238000005325 percolation Methods 0.000 claims description 7
- 239000008107 starch Substances 0.000 claims description 7
- 235000019698 starch Nutrition 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 5
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 230000036770 blood supply Effects 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 241000244365 Ligusticum sinense Species 0.000 claims 3
- 208000018262 Peripheral vascular disease Diseases 0.000 claims 1
- 206010008118 cerebral infarction Diseases 0.000 claims 1
- 241000112528 Ligusticum striatum Species 0.000 abstract 1
- 239000000284 extract Substances 0.000 description 18
- 239000013543 active substance Substances 0.000 description 16
- 229940079593 drug Drugs 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- 239000003826 tablet Substances 0.000 description 12
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
- 229960001138 acetylsalicylic acid Drugs 0.000 description 9
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 9
- 230000002785 anti-thrombosis Effects 0.000 description 8
- 239000008187 granular material Substances 0.000 description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- 239000003146 anticoagulant agent Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000001772 blood platelet Anatomy 0.000 description 6
- 235000008504 concentrate Nutrition 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 229940032147 starch Drugs 0.000 description 6
- 241000208340 Araliaceae Species 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- -1 Oral preparation Substances 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 5
- 235000003140 Panax quinquefolius Nutrition 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 235000008434 ginseng Nutrition 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000002526 effect on cardiovascular system Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010002383 Angina Pectoris Diseases 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 102000002045 Endothelin Human genes 0.000 description 3
- 108050009340 Endothelin Proteins 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YVNQAIFQFWTPLQ-UHFFFAOYSA-O [4-[[4-(4-ethoxyanilino)phenyl]-[4-[ethyl-[(3-sulfophenyl)methyl]amino]-2-methylphenyl]methylidene]-3-methylcyclohexa-2,5-dien-1-ylidene]-ethyl-[(3-sulfophenyl)methyl]azanium Chemical compound C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C(=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S(O)(=O)=O)C)C=2C(=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S(O)(=O)=O)C)C=C1 YVNQAIFQFWTPLQ-UHFFFAOYSA-O 0.000 description 3
- 210000000683 abdominal cavity Anatomy 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000015271 coagulation Effects 0.000 description 3
- 238000005345 coagulation Methods 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000003925 fat Substances 0.000 description 3
- 235000019197 fats Nutrition 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000002398 materia medica Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 239000012460 protein solution Substances 0.000 description 3
- 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 description 2
- 238000009010 Bradford assay Methods 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 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 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 241001465754 Metazoa Species 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 206010036790 Productive cough Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000003114 blood coagulation factor Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 229940126678 chinese medicines Drugs 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229940000406 drug candidate Drugs 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 239000003777 experimental drug Substances 0.000 description 2
- 239000003527 fibrinolytic agent Substances 0.000 description 2
- 230000003480 fibrinolytic effect Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 229940100688 oral solution Drugs 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 208000024794 sputum Diseases 0.000 description 2
- 210000003802 sputum Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 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 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 1
- LXAHHHIGZXPRKQ-UHFFFAOYSA-N 5-fluoro-2-methylpyridine Chemical compound CC1=CC=C(F)C=N1 LXAHHHIGZXPRKQ-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 101800000734 Angiotensin-1 Proteins 0.000 description 1
- 102400000344 Angiotensin-1 Human genes 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 101100310593 Candida albicans (strain SC5314 / ATCC MYA-2876) SOD4 gene Proteins 0.000 description 1
- 240000008574 Capsicum frutescens Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 241000721047 Danaus plexippus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 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 1
- 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 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 101000621371 Homo sapiens WD and tetratricopeptide repeats protein 1 Proteins 0.000 description 1
- 101000892274 Human adenovirus C serotype 2 Adenovirus death protein Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 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 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- PVLHOJXLNBFHDX-XHJPDDKBSA-N Panaxadiol Chemical group C[C@]1([C@H]2CC[C@@]3([C@@H]2[C@H](O)C[C@H]2[C@]3(CC[C@H]3C(C)(C)[C@@H](O)CC[C@@]32C)C)C)CCCC(C)(C)O1 PVLHOJXLNBFHDX-XHJPDDKBSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- MYHXHCUNDDAEOZ-UHFFFAOYSA-N Prostaglandin A&2% Natural products CCCCCC(O)C=CC1C=CC(=O)C1CC=CCCCC(O)=O MYHXHCUNDDAEOZ-UHFFFAOYSA-N 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 101000820656 Rattus norvegicus Seminal vesicle secretory protein 4 Proteins 0.000 description 1
- 101100190148 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PGA2 gene Proteins 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010041235 Snoring Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 206010041956 Stasis syndrome Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 208000031975 Yang Deficiency Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 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 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 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 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 208000005634 blind loop syndrome Diseases 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000001354 calcination Methods 0.000 description 1
- NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 description 1
- 229910000020 calcium bicarbonate Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940117916 cinnamic aldehyde Drugs 0.000 description 1
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000000571 coke Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960001305 cysteine hydrochloride Drugs 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 229940107131 ginseng root Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 210000003111 iliac vein Anatomy 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- GSKDBLIBBOYOFU-UHFFFAOYSA-N oxadiazol-5-amine Chemical class NC1=CN=NO1 GSKDBLIBBOYOFU-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000036581 peripheral resistance Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 208000037920 primary disease Diseases 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- MYHXHCUNDDAEOZ-FOSBLDSVSA-N prostaglandin A2 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1C=CC(=O)[C@@H]1C\C=C/CCCC(O)=O MYHXHCUNDDAEOZ-FOSBLDSVSA-N 0.000 description 1
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 210000001139 rectus abdominis Anatomy 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 210000002796 renal vein Anatomy 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 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 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 150000003376 silicon Chemical class 0.000 description 1
- 239000002893 slag Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- ZAVXXBAIPSQJGS-UHFFFAOYSA-B tetracalcium;tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O.[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O.[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ZAVXXBAIPSQJGS-UHFFFAOYSA-B 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/236—Ligusticum (licorice-root)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/482—Cassia, e.g. golden shower tree
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Definitions
- the invention relates to a new use of a medicine, in particular to a medicine preparation prepared by the traditional Chinese medicine red ginseng, Chuanxiong and Guizhi, in the preparation of an antithrombotic medicament.
- compositions such as capsule preparations prepared with traditional Chinese medicine red ginseng, Chuanxiong and Guizhi have been marketed, called: Shenui Capsule, whose main functions are: Yiqi Tongyang, promoting blood circulation and removing blood stasis. For the lack of heart, qi deficiency and blood stasis syndrome. Symptoms: Chest pain, fixed, late at night, aggravated by cold, or chilly, warm, faceless; coronary heart disease, angina see the above syndrome. Book
- Shengui Capsule has protective effect on myocardial infarction induced by coronary artery ligation and myocardial ischemia induced by vasopressin in rats; it can increase coronary flow, slow heart rate and reduce myocardial consumption The amount of oxygen reduces the peripheral resistance.
- Shenui Capsule The preparation method of Shenui Capsule is as follows:
- the red ginseng powder is added, the hook is mixed, dried, and pulverized into fine powder.
- the volatile oil is absorbed by the remaining red ginseng powder, mixed with the hook, and then mixed with the above-mentioned fine powder, added with appropriate amount of starch, mixed with hooks, filled into capsules, and made into granules, which is obtained.
- thrombosis a solid mass formed in the process. It is called thrombus (thrombus).
- blood clotting factors are constantly activated, producing thrombin, forming microfibrin, which is deposited on the intima of the blood vessels, but these traces of fibrin are constantly activated by the fibrinolytic system. Dissolved, while activated clotting factors are constantly The ground is engulfed by the mononuclear phagocytic system.
- the dynamic balance of the above coagulation system and fibrinolytic system sometimes breaks the dynamic balance under certain factors that promote the blood coagulation process, triggers the coagulation process, and forms a thrombus.
- Thrombosis not only has a prominent effect in the development of cardiovascular and cerebrovascular complications, but also platelet-derived growth factors produced by platelet aggregation have an important role in promoting the development of primary diseases of cardiovascular and cerebrovascular diseases.
- the present invention unexpectedly finds that the existing product, ginseng capsule or other dosage form prepared from the same has a good antithrombotic effect.
- the present invention provides an antithrombotic preparation using red ginseng, chuanxiong and cassia twig. drug.
- the invention provides a traditional Chinese medicine preparation, which is prepared by processing Chinese traditional medicine red ginseng, Chuanxiong and cassia twig.
- the present invention also provides for the preparation of an antithrombotic drug using the traditional Chinese medicine preparation of the present invention.
- the formulation of the traditional Chinese medicine preparation of the invention has the following composition:
- red ginseng 200-400g Preferably - red ginseng 200-400g, Chuanxiong 250_750g, cassia twig 100_300g
- the weight is calculated based on the crude drug, and the above composition can be made into 1000 pharmaceutical preparations, and the 1000 doses refer to the finished pharmaceutical preparations, such as 1000 capsules, 1000 tablets, granules 1000. Gram, oral liquid 1000ml, etc.
- each dose can be 1-100 tablets, a total of 1-1000 times.
- make 1-1000 bags take 1-100 bags each time, and take 1-1000 times in total.
- the above composition is based on the weight ratio, and can be increased or decreased according to the corresponding proportion during production.
- mass production can be in kilograms or in tons, and small-scale production can also be in milligrams. It can be increased or decreased, but the ratio of the weight ratio of the raw medicinal materials between the components does not change.
- the ratio of the above weight ratios is scientifically screened, for special patients, such as severe or mild, fat
- the proportion of the composition can be adjusted accordingly, increasing or decreasing by no more than 100%, and the efficacy is unchanged.
- the single-flavored traditional Chinese medicines in the above composition such as monarch, medicine and adjuvant, can also be replaced by appropriate Chinese medicines with the same medicinal properties, and the traditional Chinese medicine preparations after replacement have the same drug action.
- the traditional Chinese medicine preparation of the present invention is prepared by extracting or otherwise processing the traditional Chinese medicine raw material composed of the above formula to prepare a pharmaceutically active substance, and then using the substance as a raw material, if necessary, adding a pharmaceutically acceptable carrier, according to the routine of preparation Made of technology.
- the active substance may be obtained by separately extracting a traditional Chinese medicine raw material, or may be obtained by jointly extracting a traditional Chinese medicine raw material, or may be obtained by other methods, such as: by pulverizing, pressing, calcining, grinding, sieving, seepage, extraction, water extraction , alcohol extraction, ester extraction, ketone extraction, chromatography, etc., these active substances may be in the form of extracts, which may be dry extracts or flow extracts, depending on the needs of the preparation, different concentrations are determined. .
- the pharmaceutically active substance in the traditional Chinese medicine preparation of the present invention may be any pharmaceutically active substance.
- the weight percentage thereof in the preparation may be any pharmaceutically active substance.
- the pharmaceutical preparation of the present invention is in the form of a unit dosage form, which means a unit of the preparation, such as each tablet of the tablet, each capsule of the capsule, each bottle of the oral solution, granules per bag, and the like.
- the traditional Chinese medicine preparation of the present invention may be any pharmaceutically acceptable dosage form, and the preparation forms include: tablets, sugar-coated tablets, film-coated tablets, enteric coated tablets, capsules, hard capsules, soft capsules, oral liquids, Oral preparation, granules, granules, pills, pills, powders, ointments, dans, suspensions, powders, solutions, injections, suppositories, ointments, plasters, creams, sprays, drops, stickers Agent.
- the preparation of the present invention is preferably an oral dosage form such as a capsule, a tablet, an oral solution, a granule, a pill, a powder, an agent, a paste or the like. Most preferred is a capsule, i.e., a ginseng capsule of the present invention.
- the preparation for oral administration may contain common excipients such as a binder, a filler, a diluent, a compressed tablet, a lubricant, a disintegrant, a coloring agent, a flavoring agent and a wetting agent.
- a binder such as a binder, a filler, a diluent, a compressed tablet, a lubricant, a disintegrant, a coloring agent, a flavoring agent and a wetting agent.
- Suitable fillers include cellulose, mannitol, lactose and other similar fillers.
- Suitable disintegrants include starch, polyvinylpyrrolidone and starch derivatives such as sodium starch glycolate.
- Suitable lubricants include, for example, magnesium stearate.
- Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulfate.
- the solid oral composition can be prepared by a usual method such as mixing, filling, tableting or the like. Repeated mixing allows the active material to be distributed throughout those compositions that use large amounts of filler.
- the oral liquid preparation may be in the form of, for example, an aqueous or oily suspension, solution, emulsion, syrup or elixir, or may be a dry product which may be formulated with water or other suitable carrier before use.
- Such liquid preparations may contain conventional additives such as suspending agents such as sorbitol, syrup, methylcellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate or hydrogenated edible fats.
- Emulsifiers such as lecithin, sorbitan monooleate or gum arabic; non-aqueous carriers (which may include edible oils), such as almond oil, fractionated coconut oil, oily esters of esters such as glycerol, propylene glycol or ethanol;
- the agent for example, p-hydroxybenzyl or propylparaben or sorbic acid, and if desired, may contain conventional flavoring or coloring agents.
- the liquid unit dosage form prepared contains the active substance of the invention and a sterile vehicle.
- This compound can be suspended or dissolved depending on the carrier and concentration.
- the solution is usually prepared by dissolving the active substance in a carrier, sterilizing it by filtration before filling it into a suitable vial or ampoule, and then sealing. Excipients such as a local anesthetic, preservative and buffer may also be dissolved in such a carrier.
- the composition can be frozen after filling the vial and the water removed under vacuum.
- the traditional Chinese medicine preparation of the present invention can be selectively added to a suitable pharmaceutically acceptable carrier when prepared as a medicament, the pharmaceutically acceptable carrier being selected from the group consisting of: mannitol, sorbitol, sodium metabisulfite, sodium hydrogen sulfite, thio Sodium sulfate, cysteine hydrochloride, thioglycolic acid, methionine, vitamins (:, EDTA disodium, EDTA calcium sodium, monovalent alkali metal carbonate, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulfuric acid , phosphoric acid, amino acid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivatives, cellulose and their derivatives , alginate, gelatin, polyvinylpyrrolidone,
- the preparation of the invention is used according to the condition of the patient at the time of use, and can be taken two to four times a day, each time.
- 1-20 doses such as: 1-20 bags or tablets or tablets.
- the traditional Chinese medicine preparation of the present invention can be produced by the following method.
- the volatile oil is adsorbed by the remaining red ginseng fine powder, mixed and hooked, and then mixed with the above fine powder to obtain the pharmaceutically active substance of the present invention.
- the pharmaceutically active substance is mixed with a pharmaceutically acceptable carrier, and a pharmaceutical preparation of the invention can be prepared by a conventional technique of formulation.
- the pharmaceutical preparation of the present invention is particularly suitable and applied to antithrombotic formation. For this reason, the present invention provides an application for preparing an antithrombotic drug using the pharmaceutical preparation of the present invention.
- Yudan ® Shenui Capsule According to the body surface area, the amount of rats was converted into the amount of rats, high dose group L 8g / kg, medium dose group 0. 9g / kg, low dose group 0. 45g / kg. Weigh the required amount, add distilled water, and make a suspension of 1. 8g / ml, 0.9g / ml, 0. 45g / ml, respectively, 0. lml / 100g (body weight) by gastric administration. Aspirin: According to the body surface area, the clinical dose of lOOmg / day is converted into the amount of rats, 9mg / kg. Weigh the required amount, add distilled water, make a 9mg/ml suspension, and use 0.1 ml/100g (body weight) for gastric administration.
- a small iron micro-pressure spring was implanted in the direction of the renal vein in the caudal iliac vein of the tail vein to suppress hemostasis. Close the abdominal cavity. After 2 hours, open the abdominal cavity, take out the stainless iron micro-pressure spring and the thrombus together, wash gently with physiological saline, and absorb excess water. The compression spring and the thrombus were placed in 2 ml of an alkaline sodium carbonate solution (100 mmol/L sodium hydroxide, 2% sodium carbonate), and placed in a boiling water bath for 3 min. The protein content in the 100 ⁇ ⁇ sample was determined by the Coomassie brilliant blue method (Bradford method).
- test tubes Take the test tubes as needed and divide them into two groups. A set of standard protein solutions with 1.0 mg/ml were added to each tube: 0 (for blank), 0. 005, 0. 01, 0. 02, 0. 03, 0. 04, 0. 05ml, then 0 ⁇ Adding with 0. 05ml. The rest is left as an unknown sample. 0. 05ml sample solution per tube. Finally, add 2. 5 ml of Coomassie Brilliant G-250 Reagent to each tube and mix immediately on the vortex mixer after each tube.
- the data indicates the degree of thrombosis by the standard deviation of the mean value of thrombus protein content, and the degree of thrombosis is high in patients with high protein content. Statistical significance was compared between groups using the t test.
- Shengui Capsule In the Shenui Capsule, the red ginseng and the qi, the Guizhi Wenyang, and the Chuanxiong Tongmai are used for the chest sputum with yang deficiency and qi deficiency and blood stasis.
- Pharmacological studies reported in related literature mostly involve the mechanism of cardiac dysfunction.
- the mechanism of action of Shengui Capsule in treating cardiac dysfunction is related to its intervention in myocardial remodeling and inhibition of cardiomyocyte apoptosis, and it also reduces plasma endothelin (ET). , angiotensin i Arig ll) level and other effects.
- E plasma endothelin
- angiotensin i Arig ll angiotensin i Arig ll
- Intraperitoneal injection of Guizhi injection can relieve red blood cell and platelet aggregation in rabbit experimental limb snoring model and improve tissue blood circulation. Cinnamaldehyde inhibits platelet aggregation in vitro. Chuanxiong and Chuanxiong have significant inhibitory effects on rabbit and human platelet aggregation induced by ADP, collagen and thrombin in vitro, and rapidly disaggregate the aggregated platelets. Chuanxiong can inhibit platelet aggregation in allergic asthma guinea pigs and sepsis rabbits. Cardiovascular and cerebrovascular patients can take red blood cells and platelet surface after taking Chuanxiong The charge increases and the aggregation decreases.
- the mechanism by which Chuanxiong inhibits platelet aggregation may be related to inhibition of intracellular Ca ++ release, affecting the balance between TXA2/PGI2, and replacement of platelet membrane Ca ++ to increase membrane negative charge, and may also be related to (Chuangchuan and Chuanxiong injections). ) Increased (mouse plasma and rabbit platelet suspension) effects on cAMP levels.
- Shenui Capsule By inhibiting the formation of intravascular thrombus and preventing some pathological links in the development of vascular lesions, Shenui Capsule can not only improve the coronary blood supply of the heart, but also can be used for the prevention of peripheral blood vessels and cerebrovascular diseases.
- Example 3 The pharmaceutically active substance of Example 1 was added with an appropriate amount of starch, mixed, and granulated, and 1000 capsules were obtained.
- Example 3 The pharmaceutically active substance of Example 1 was added with an appropriate amount of starch, mixed, and granulated, and 1000 capsules were obtained.
- Example 4 The pharmaceutically active substance of Example 1 was added with an appropriate amount of starch, mixed, and granulated, and compressed into 1000 pieces to obtain.
- Example 4 The pharmaceutically active substance of Example 1 was added with an appropriate amount of starch, mixed, and granulated, and compressed into 1000 pieces to obtain.
- Example 5 The pharmaceutically active substance of Example 1 was added with an appropriate amount of starch, sucrose, and a hook to make 1000 g, and packaged into 2 g/bag, which was obtained.
- Example 5 The pharmaceutically active substance of Example 1 was added with an appropriate amount of starch, sucrose, and a hook to make 1000 g, and packaged into 2 g/bag, which was obtained.
- Thick paste add red ginseng powder, mix with hook, dry, pulverize into fine powder.
- the volatile oil is adsorbed by the remaining red ginseng fine powder, mixed, and then mixed with the above fine powder to obtain the pharmaceutically active substance of the present invention.
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
An application of Shengui capsule in preparing antithrombotic drugs. The Shengui capsule is prepared by using such traditional Chinese medicines as red ginseng, ligusticum wallichii, and cassia twig.
Description
参桂胶囊在制备抗血栓药物中的应用 Application of Shenui Capsule in Preparation of Antithrombotic Drugs
技术领域: Technical field:
本发明涉及一种药物的新用途, 特别是用中药红参, 川芎, 桂枝制备的药物制剂 参桂胶囊在制备抗血栓的药物中的应用。 The invention relates to a new use of a medicine, in particular to a medicine preparation prepared by the traditional Chinese medicine red ginseng, Chuanxiong and Guizhi, in the preparation of an antithrombotic medicament.
背景技术: 说 Background Art:
用中药红参, 川芎,桂枝制备的药物制剂如胶囊制剂已经上市,称为:参桂胶囊, 其功能主治是: 益气通阳, 活血化瘀。 用于心阳不振, 气虚血瘀证。 症见: 胸部 剌痛、 固定不移、 入夜更甚、 遇冷加重, 或畏寒喜暖, 面色少华; 冠心病、 心绞 痛见上述证候者。 书 Pharmaceutical preparations such as capsule preparations prepared with traditional Chinese medicine red ginseng, Chuanxiong and Guizhi have been marketed, called: Shenui Capsule, whose main functions are: Yiqi Tongyang, promoting blood circulation and removing blood stasis. For the lack of heart, qi deficiency and blood stasis syndrome. Symptoms: Chest pain, fixed, late at night, aggravated by cold, or chilly, warm, faceless; coronary heart disease, angina see the above syndrome. Book
药理作用研究表明:参桂胶囊对冠脉结扎所致大鼠心肌梗塞和垂体后叶素所致大 鼠心肌缺血有一定的保护作用;能增加犬冠脉流量,减慢心率,降低心肌耗氧量, 降低外周阻力。 Pharmacological studies have shown that: Shengui Capsule has protective effect on myocardial infarction induced by coronary artery ligation and myocardial ischemia induced by vasopressin in rats; it can increase coronary flow, slow heart rate and reduce myocardial consumption The amount of oxygen reduces the peripheral resistance.
参桂胶囊的制备方法如下: The preparation method of Shenui Capsule is as follows:
原料: 红参, 川芎, 桂枝 Ingredients: Red Ginseng, Chuanxiong, Guizhi
以上三味, 取红参, 粉碎成细粉, 备用; 剩余的红参粉碎成粗粉, 照流浸膏剂与 浸膏剂项下的渗漉法 (中国药典 2000年版一部附录 I 0), 用乙醇作溶剂进行渗 漉, 收集渗漉液, 备用; 川芎、 桂枝加水蒸馏提取挥发油, 收集挥发油, 备用; 蒸馏液滤过, 滤液备用; 药渣与上述红参药渣加水煎煮二次, 滤过, 滤液合并, 浓缩, 放冷, 加乙醇, 放置, 滤过 , 滤液与红参渗漉液合并, 回收乙醇并浓缩 至稠膏状, 加红参细粉, 拌勾, 干燥, 粉碎成细粉。 挥发油用剩余的红参细粉吸 附, 混勾, 再与上述细粉混勾, 加入适量的淀粉, 混勾, 装入胶囊, 制成粒, 即 得。 The above three flavors, take red ginseng, pulverize into fine powder, spare; the remaining red ginseng is pulverized into coarse powder, and the percolation method under the extract of extract and extract (Chinese Pharmacopoeia 2000 edition, Appendix I 0), with ethanol Solvent for percolation, collecting percolate, standby; Chuanxiong, Guizhi plus water distillation to extract volatile oil, collect volatile oil, spare; distillate filtered, filtrate for use; medicinal residue and red ginseng residue simmered twice with water, filter The filtrate is combined, concentrated, allowed to cool, added with ethanol, placed, filtered, and the filtrate is combined with the red ginseng osmosis solution, and the ethanol is recovered and concentrated to a thick paste. The red ginseng powder is added, the hook is mixed, dried, and pulverized into fine powder. The volatile oil is absorbed by the remaining red ginseng powder, mixed with the hook, and then mixed with the above-mentioned fine powder, added with appropriate amount of starch, mixed with hooks, filled into capsules, and made into granules, which is obtained.
在活体的心脏或血管腔内,血液发生凝固或血液中的某些有形成分互相粘集, 形 成固体质块的过程, 称为血栓形成 (thrombosis ) , 在这个过程中所形成的固体 质块称为血栓 (thrombus )。 在生理状态下, 血液中的凝血因子不断地被激活, 从而产生凝血酶, 形成微量纤维蛋白, 沉着于血管内膜上, 但这些微量的纤维蛋 白又不断地被激活了的纤维蛋白溶解系统所溶解,同时被激活的凝血因子也不断
地被单核吞噬细胞系统所吞噬。 上述凝血系统和纤维蛋白溶解系统的动态平衡, 有时在某些能促进凝血过程的因素作用下, 打破动态平衡, 触发凝血过程, 形成 血栓。 In the heart or vascular lumen of a living body, the process of coagulation of blood or the formation of solid particles in the blood to form a solid mass, called thrombosis, a solid mass formed in the process. It is called thrombus (thrombus). Under physiological conditions, blood clotting factors are constantly activated, producing thrombin, forming microfibrin, which is deposited on the intima of the blood vessels, but these traces of fibrin are constantly activated by the fibrinolytic system. Dissolved, while activated clotting factors are constantly The ground is engulfed by the mononuclear phagocytic system. The dynamic balance of the above coagulation system and fibrinolytic system sometimes breaks the dynamic balance under certain factors that promote the blood coagulation process, triggers the coagulation process, and forms a thrombus.
血栓形成不仅在心脑血管并发症发生中具有突出的影响,而且由血小板聚集产生 的血小板衍生生长因子等对引起心脑血管病的原发病的发展亦有重要的促进作 用。 Thrombosis not only has a prominent effect in the development of cardiovascular and cerebrovascular complications, but also platelet-derived growth factors produced by platelet aggregation have an important role in promoting the development of primary diseases of cardiovascular and cerebrovascular diseases.
现有中药能够抗血栓的不多, 而且大多疗效不佳, Existing Chinese medicines are not able to resist thrombosis, and most of them are not effective.
本发明意外的发现,现有产品参桂胶囊或由其配方制备成的其他剂型具有良好的 抗血栓形成的作用, 为此, 本发明提供用红参, 川芎, 桂枝制备一种抗血栓的药 物。 The present invention unexpectedly finds that the existing product, ginseng capsule or other dosage form prepared from the same has a good antithrombotic effect. To this end, the present invention provides an antithrombotic preparation using red ginseng, chuanxiong and cassia twig. drug.
发明内容: Summary of the invention:
本发明提供一种中药制剂, 该制剂由中药红参, 川芎, 桂枝经过加工制备而成。 本发明还提供用本发明的中药制剂制备一种抗血栓形成的药物。 The invention provides a traditional Chinese medicine preparation, which is prepared by processing Chinese traditional medicine red ginseng, Chuanxiong and cassia twig. The present invention also provides for the preparation of an antithrombotic drug using the traditional Chinese medicine preparation of the present invention.
本发明的中药制剂其配方组成如下: The formulation of the traditional Chinese medicine preparation of the invention has the following composition:
红参 l-1000g, 川芎 l-1000g, 桂枝 l-1000g Red ginseng l-1000g, Chuanxiong l-1000g, cassia twig l-1000g
优选的是- 红参 200- 400g, 川芎 250_750g, 桂枝 100_300g Preferably - red ginseng 200-400g, Chuanxiong 250_750g, cassia twig 100_300g
最优选的是: Most preferred is:
红参 300g, 川芎 500g, 桂枝 200g Red Ginseng 300g, Chuanxiong 500g, Guizhi 200g
以上组成中,重量是以生药计算的,以上组成可制成药物制剂 1000剂,所述 1000 剂指, 制成的成品药物制剂, 如制成胶囊制剂 1000粒, 片剂 1000片, 颗粒剂 1000克, 口服液 1000ml等。 In the above composition, the weight is calculated based on the crude drug, and the above composition can be made into 1000 pharmaceutical preparations, and the 1000 doses refer to the finished pharmaceutical preparations, such as 1000 capsules, 1000 tablets, granules 1000. Gram, oral liquid 1000ml, etc.
以上组成, 若以克为单位, 可制成 1000次服用剂量的制剂, 如作为片剂, 制成 1000片, 每次服用剂量可以是 1-100片, 共可服用 1-1000次。 如作为颗粒剂, 制成 1-1000袋, 每次服用 1-100袋, 共可服用 1-1000次。 The above composition, if in grams, can be made into 1000 doses of the preparation, such as tablets, made into 1000 tablets, each dose can be 1-100 tablets, a total of 1-1000 times. For example, as a granule, make 1-1000 bags, take 1-100 bags each time, and take 1-1000 times in total.
以上组成是按重量份作为配比的,在生产时可按照相应比例增大或减少, 如大规 模生产可以以公斤为单位, 或以吨为单位, 小规模生产也可以以毫克为单位, 重 量可以增大或者减小, 但各组成之间的生药材重量配比的比例不变。 The above composition is based on the weight ratio, and can be increased or decreased according to the corresponding proportion during production. For example, mass production can be in kilograms or in tons, and small-scale production can also be in milligrams. It can be increased or decreased, but the ratio of the weight ratio of the raw medicinal materials between the components does not change.
以上重量配比的比例是经过科学筛选得到的, 对于特殊病人, 如重症或轻症, 肥
胖或痩小的病人, 可以相应调整组成的量的配比, 增加或减少不超过 100%, 药 效不变。 The ratio of the above weight ratios is scientifically screened, for special patients, such as severe or mild, fat For fat or small patients, the proportion of the composition can be adjusted accordingly, increasing or decreasing by no more than 100%, and the efficacy is unchanged.
以上组成中的单味中药, 如君药、 臣药和佐药, 也可以被适当的具有相同药性的 中药替换, 替换后的中药制剂其药物作用不变。 The single-flavored traditional Chinese medicines in the above composition, such as monarch, medicine and adjuvant, can also be replaced by appropriate Chinese medicines with the same medicinal properties, and the traditional Chinese medicine preparations after replacement have the same drug action.
本发明的中药制剂, 是通过将上述配方组成的中药原料经过提取或其他方式加 工,制成药物活性物质, 随后, 以该物质为原料, 需要时加入药物可接受的载体, 按照制剂学的常规技术制成的。 所述活性物质可以通过分别提取中药原料得到, 也可以通过共同提取中药原料得到, 也可以通过其他方式得到, 如: 通过粉碎、 压搾、 煅烧、 研磨、 过筛、 渗漉、 萃取、 水提、 醇提、 酯提、 酮提、 层析等方法 得到、这些活性物质可以是浸膏形式的物质, 可以是干浸膏也可以是流浸膏, 根 据制剂的不同需要决定制成不同的浓度。 The traditional Chinese medicine preparation of the present invention is prepared by extracting or otherwise processing the traditional Chinese medicine raw material composed of the above formula to prepare a pharmaceutically active substance, and then using the substance as a raw material, if necessary, adding a pharmaceutically acceptable carrier, according to the routine of preparation Made of technology. The active substance may be obtained by separately extracting a traditional Chinese medicine raw material, or may be obtained by jointly extracting a traditional Chinese medicine raw material, or may be obtained by other methods, such as: by pulverizing, pressing, calcining, grinding, sieving, seepage, extraction, water extraction , alcohol extraction, ester extraction, ketone extraction, chromatography, etc., these active substances may be in the form of extracts, which may be dry extracts or flow extracts, depending on the needs of the preparation, different concentrations are determined. .
本发明的中药制剂中的药物活性物质, 其在制剂中所占重量百分比可以是The pharmaceutically active substance in the traditional Chinese medicine preparation of the present invention, the weight percentage thereof in the preparation may be
0. 1-99. 9%, 其余为药物可接受的载体。 本发明的药物制剂, 以单位剂量形式存 在, 所述单位剂量形式是指制剂的单位, 如片剂的每片, 胶囊的每粒胶囊, 口服 液的每瓶, 颗粒剂每袋等。 0. 1-99. 9%, the remainder being a pharmaceutically acceptable carrier. The pharmaceutical preparation of the present invention is in the form of a unit dosage form, which means a unit of the preparation, such as each tablet of the tablet, each capsule of the capsule, each bottle of the oral solution, granules per bag, and the like.
本发明的中药制剂可以是任何可药用的剂型, 这些剂型包括: 片剂、 糖衣片剂、 薄膜衣片剂、 肠溶衣片剂、 胶囊剂、 硬胶囊剂、 软胶囊剂、 口服液、 口含剂、 颗 粒剂、 冲剂、 丸剂、 滴丸、 散剂、 膏剂、 丹剂、 混悬剂、 粉剂、 溶液剂、 注射剂、 栓剂、 软膏剂、 硬膏剂、 霜剂、 喷雾剂、 滴剂、 贴剂。 本发明的制剂, 优选的是 口服剂型, 如: 胶囊剂、 片剂、 口服液、 颗粒剂、 丸剂、 散剂、 丹剂、 膏剂等。 最优选的是胶囊剂, 即本发明所述参桂胶囊。 The traditional Chinese medicine preparation of the present invention may be any pharmaceutically acceptable dosage form, and the preparation forms include: tablets, sugar-coated tablets, film-coated tablets, enteric coated tablets, capsules, hard capsules, soft capsules, oral liquids, Oral preparation, granules, granules, pills, pills, powders, ointments, dans, suspensions, powders, solutions, injections, suppositories, ointments, plasters, creams, sprays, drops, stickers Agent. The preparation of the present invention is preferably an oral dosage form such as a capsule, a tablet, an oral solution, a granule, a pill, a powder, an agent, a paste or the like. Most preferred is a capsule, i.e., a ginseng capsule of the present invention.
本发明的中药制剂, 其口服给药的制剂可含有常用的赋形剂, 诸如粘合剂、填充 剂、 稀释剂、 压片剂、 润滑剂、 崩解剂、 着色剂、 调味剂和湿润剂, 必要时可对 片剂进行包衣。 The traditional Chinese medicine preparation of the present invention, the preparation for oral administration may contain common excipients such as a binder, a filler, a diluent, a compressed tablet, a lubricant, a disintegrant, a coloring agent, a flavoring agent and a wetting agent. , The tablets can be coated if necessary.
适用的填充剂包括纤维素、甘露糖醇、 乳糖和其它类似的填充剂。适宜的崩解剂 包括淀粉、聚乙烯吡咯烷酮和淀粉衍生物, 例如羟基乙酸淀粉钠。适宜的润滑剂 包括, 例如硬脂酸镁。 适宜的药物可接受的湿润剂包括十二烷基硫酸钠。 Suitable fillers include cellulose, mannitol, lactose and other similar fillers. Suitable disintegrants include starch, polyvinylpyrrolidone and starch derivatives such as sodium starch glycolate. Suitable lubricants include, for example, magnesium stearate. Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulfate.
可通过混合, 填充, 压片等常用的方法制备固体口服组合物。进行反复混合可使 活性物质分布在整个使用大量填充剂的那些组合物中。
口服液体制剂的形式例如可以是水性或油性悬浮液、溶液、乳剂、糖浆剂或酏剂, 或者可以是一种在使用前可用水或其它适宜的载体复配的干燥产品。这种液体制 剂可含有常规的添加剂, 诸如悬浮剂, 例如山梨醇、 糖浆、 甲基纤维素、 明胶、 羟乙基纤维素、 羧甲基纤维素、 硬脂酸铝凝胶或氢化食用脂肪, 乳化剂, 例如卵 磷脂、 脱水山梨醇一油酸酯或阿拉伯胶; 非水性载体 (它们可以包括食用油), 例如杏仁油、 分馏椰子油、 诸如甘油的酯的油性酯、 丙二醇或乙醇; 防腐剂, 例 如对羟基苯甲酯或对羟基苯甲酸丙酯或山梨酸, 并且如果需要,可含有常规的香 味剂或着色剂。 The solid oral composition can be prepared by a usual method such as mixing, filling, tableting or the like. Repeated mixing allows the active material to be distributed throughout those compositions that use large amounts of filler. The oral liquid preparation may be in the form of, for example, an aqueous or oily suspension, solution, emulsion, syrup or elixir, or may be a dry product which may be formulated with water or other suitable carrier before use. Such liquid preparations may contain conventional additives such as suspending agents such as sorbitol, syrup, methylcellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate or hydrogenated edible fats. Emulsifiers such as lecithin, sorbitan monooleate or gum arabic; non-aqueous carriers (which may include edible oils), such as almond oil, fractionated coconut oil, oily esters of esters such as glycerol, propylene glycol or ethanol; The agent, for example, p-hydroxybenzyl or propylparaben or sorbic acid, and if desired, may contain conventional flavoring or coloring agents.
对于注射剂,制备的液体单位剂型含有本发明的活性物质和无菌载体。根据载体 和浓度,可以将此化合物悬浮或者溶解。溶液的制备通常是通过将活性物质溶解 在一种载体中, 在将其装入一种适宜的小瓶或安瓿前过滤消毒, 然后密封。辅料 例如一种局部麻醉剂、防腐剂和缓冲剂也可以溶解在这种载体中。为了提高其稳 定性, 可在装入小瓶以后将这种组合物冰冻, 并在真空下将水除去。 For injection, the liquid unit dosage form prepared contains the active substance of the invention and a sterile vehicle. This compound can be suspended or dissolved depending on the carrier and concentration. The solution is usually prepared by dissolving the active substance in a carrier, sterilizing it by filtration before filling it into a suitable vial or ampoule, and then sealing. Excipients such as a local anesthetic, preservative and buffer may also be dissolved in such a carrier. To increase its stability, the composition can be frozen after filling the vial and the water removed under vacuum.
本发明的中药制剂, 在制备成药剂时可选择性的加入适合的药物可接受的载体, 所述药物可接受的载体选自: 甘露醇、 山梨醇、 焦亚硫酸钠、 亚硫酸氢钠、 硫代硫酸钠、 盐酸半胱氨酸、 巯基乙酸、 蛋氨酸、 维生素 (:、 EDTA二钠、 EDTA 钙钠, 一价碱金属的碳酸盐、 醋酸盐、 磷酸盐或其水溶液、 盐酸、 醋酸、 硫酸、 磷酸、 氨基酸、 氯化钠、 氯化钾、 乳酸钠、 木糖醇、 麦芽糖、 葡萄糖、 果糖、 右 旋糖苷、甘氨酸、淀粉、蔗糖、 乳糖、甘露糖醇、硅衍生物、纤维素及其衍生物、 藻酸盐、 明胶、 聚乙烯吡咯烷酮、 甘油、 土温 80、 琼脂、 碳酸钙、 碳酸氢钙、 表面活性剂、 聚乙二醇、 环糊精、 β—环糊精、 磷脂类材料、 高岭土、 滑石粉、 硬脂酸钙、 硬脂酸镁等。 The traditional Chinese medicine preparation of the present invention can be selectively added to a suitable pharmaceutically acceptable carrier when prepared as a medicament, the pharmaceutically acceptable carrier being selected from the group consisting of: mannitol, sorbitol, sodium metabisulfite, sodium hydrogen sulfite, thio Sodium sulfate, cysteine hydrochloride, thioglycolic acid, methionine, vitamins (:, EDTA disodium, EDTA calcium sodium, monovalent alkali metal carbonate, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulfuric acid , phosphoric acid, amino acid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivatives, cellulose and their derivatives , alginate, gelatin, polyvinylpyrrolidone, glycerin, earth temperature 80, agar, calcium carbonate, calcium bicarbonate, surfactant, polyethylene glycol, cyclodextrin, beta-cyclodextrin, phospholipids, Kaolin, talc, calcium stearate, magnesium stearate, etc.
本发明的制剂在使用时根据病人的情况确定用法用量, 可每日服二-四次, 每次The preparation of the invention is used according to the condition of the patient at the time of use, and can be taken two to four times a day, each time.
1-20剂, 如: 1-20袋或粒或片。 1-20 doses, such as: 1-20 bags or tablets or tablets.
本发明的中药制剂可以通过以下方法制备。 The traditional Chinese medicine preparation of the present invention can be produced by the following method.
取红参, 粉碎成细粉, 备用; 剩余的红参粉碎成粗粉, 照流浸膏剂与浸膏剂项下 的渗漉法 (中国药典 2000年版一部附录 I 0), 用乙醇作溶剂进行渗漉, 收集渗 漉液, 备用; 川芎、桂枝加水蒸馏提取挥发油, 收集挥发油, 备用; 蒸馏液滤过, 滤液备用; 药渣与上述红参药渣加水煎煮二次, 滤过, 滤液合并, 浓缩, 放冷,
加乙醇, 放置, 滤过 , 滤液与红参渗漉液合并, 回收乙醇并浓缩至稠膏状, 加 红参细粉, 拌勾, 干燥, 粉碎成细粉。 挥发油用剩余的红参细粉吸附, 混勾, 再 与上述细粉混勾, 即得本发明的药物活性物质。将该药物活性物质与药物可接受 的载体混合, 用制剂学常规技术, 可制备成本发明的药物制剂。 Take red ginseng, pulverize into fine powder, spare; the remaining red ginseng is pulverized into coarse powder, and the percolation method under the extract of extract and extract (Chinese Pharmacopoeia 2000 edition, Appendix I 0), using ethanol as solvent Seepage, collect the seepage solution, reserve; Chuanxiong, Guizhi add water to extract volatile oil, collect volatile oil, reserve; distillate filtered, the filtrate is reserved; the dregs and the above red ginseng residue are decoctioned twice, filtered, filtrate Consolidate, concentrate, let cool, Add ethanol, place, filter, and combine the filtrate with red ginseng osmosis solution, recover ethanol and concentrate to thick paste, add red ginseng powder, mix with hook, dry, pulverize into fine powder. The volatile oil is adsorbed by the remaining red ginseng fine powder, mixed and hooked, and then mixed with the above fine powder to obtain the pharmaceutically active substance of the present invention. The pharmaceutically active substance is mixed with a pharmaceutically acceptable carrier, and a pharmaceutical preparation of the invention can be prepared by a conventional technique of formulation.
本发明的药物制剂, 特别适合并应用于抗血栓形成, 为此, 本发明提供用本发明的药物 剂制备一种抗血栓形成的药物中的应用。 The pharmaceutical preparation of the present invention is particularly suitable and applied to antithrombotic formation. For this reason, the present invention provides an application for preparing an antithrombotic drug using the pharmaceutical preparation of the present invention.
本发明的应用是通过对本发明的药物,特别是参桂胶囊进行了新的药效研究后意 外发现的, 而且与现有技术相比取得了意想不到的结果, 以下为实验研究数据。 参桂胶囊抗血栓形成的实验研究 The application of the present invention has been unexpectedly discovered by conducting a new pharmacodynamic study on the drug of the present invention, particularly Shenui Capsule, and has achieved unexpected results compared with the prior art. The following are experimental research data. Experimental study on anti-thrombosis of Shenui Capsule
1. 实验材料 Experimental material
1. 1 实验药物: 玉丹 ®参桂胶囊, 临床用量: 每次 3— 4粒 (每粒内容物 0. 3g), 每天 3次口服。 由上海玉丹药业有限公司提供, 批号: 20090801。 阿司匹林, 临 床用量: lOOmg/次 /日口服。 由上海医药 (集团) 有限公司信谊制药总厂产品, 批号: 090201。 考马斯亮蓝 G250, 北京鼎国生物技术有限责任公司产品, 批号: 7AD10349。 牛血清白蛋白, 华美生物工程公司产品, 批号: 0103。 1. 1 Experimental drug: Yudan ® Shenui Capsule, clinical dosage: 3-4 capsules each time (each content is 0. 3g), orally 3 times a day. Provided by Shanghai Yudan Pharmaceutical Co., Ltd., batch number: 20090801. Aspirin, clinical use: lOOmg / time / day orally. Product by Xinyi Pharmaceutical General Factory of Shanghai Pharmaceutical (Group) Co., Ltd., batch number: 090201. Coomassie Brilliant Blue G250, Beijing Dingguo Biotechnology Co., Ltd., batch number: 7AD10349. Bovine serum albumin, product of Huamei Bioengineering Co., Ltd., batch number: 0103.
1. 2 实验动物: SD大鼠, 雄性, SPF级, 体重 260_300g。 由上海中医药大学实 验动物中心提供, 合格证号: SCXK (沪) 2008-0016。 1. 2 Experimental animals: SD rats, male, SPF grade, weighing 260_300g. Provided by the Experimental Animal Center of Shanghai University of Traditional Chinese Medicine, certificate number: SCXK (Shanghai) 2008-0016.
1. 3 实验器材:紫外可见分光光度计,型号 Agilent8453, Agilent Technologies 公司生产。 不锈铁微型压簧, 上海海伟弹簧厂产品, 规格 0. 8mm (内径)。 1. 3 Experimental equipment: UV-visible spectrophotometer, model Agilent 8453, manufactured by Agilent Technologies. Stainless iron micro compression spring, Shanghai Haiwei spring factory products, specifications 0. 8mm (inside diameter).
2 方法与步骤 2 methods and steps
2. 1 药物配法及用法: 2. 1 drug formulation and usage:
玉丹 ®参桂胶囊: 按体表面积以人的临床用量折算成大鼠用量, 高剂量组 L 8g/kg、 中剂量组 0. 9g/kg、 低剂量组 0. 45g/kg。 称取所需的药量, 添加蒸馏 水, 分别制成 1. 8g/ml、 0. 9g/ml、 0. 45g/ml 的混悬液, 0. lml/100g (体重) 灌 胃给药。阿司匹林:按体表面积, 以临床用量 lOOmg/日折算成大鼠用量, 9mg/kg。 称取所需的药量, 添加蒸馏水, 制成 9mg/ml的混悬液, 0. lml/100g (体重) 灌 胃给药。 Yudan ® Shenui Capsule: According to the body surface area, the amount of rats was converted into the amount of rats, high dose group L 8g / kg, medium dose group 0. 9g / kg, low dose group 0. 45g / kg. Weigh the required amount, add distilled water, and make a suspension of 1. 8g / ml, 0.9g / ml, 0. 45g / ml, respectively, 0. lml / 100g (body weight) by gastric administration. Aspirin: According to the body surface area, the clinical dose of lOOmg / day is converted into the amount of rats, 9mg / kg. Weigh the required amount, add distilled water, make a 9mg/ml suspension, and use 0.1 ml/100g (body weight) for gastric administration.
2. 2实验方法及步骤: 2. 2 experimental methods and steps:
参照文献 [7、 8], SD大鼠 90只, SPF级, 雄性, 体重 260_300g。 体重均衡后随
机分 6组: 空白对照组 20只, 给予等量生理盐水; 参桂胶囊高剂量组、 中剂量 组、 低剂量组、 阳性对照组, 参桂胶囊中剂量组与阳性药联合用药组, 每组 15 只。 各组大鼠均每日灌胃给药 1次, 连续 7天, 末次药后 60min, 以 10%乌拉坦 lml/100g 腹腔麻醉, 仰位固定于大鼠恒温 (37°C ) 手术台上, 实施手术。 弯剪 剪去腹部的毛, 正中切开腹部皮肤, 钝性剥离分离腹直肌, 进入腹腔。 于尾部腔 静脉平髂静脉向肾静脉下方向植入不锈铁微型压簧, 压迫止血。 关上腹腔。 2h 后, 打开腹腔, 将不锈铁微型压簧及血栓一同取出, 用生理盐水轻洗, 吸去多余 水分。将压簧及血栓放入 2ml碱性碳酸钠溶液(lOOmmol/L氢氧化钠, 2%碳酸钠), 置沸水浴中 3min。 100 μ ΐ样品中蛋白质含量用考马斯亮兰法(Bradford法)测 定。 References [7, 8], 90 SD rats, SPF grade, male, weight 260_300g. Balanced weight The machine was divided into 6 groups: 20 blank control groups, given the same amount of normal saline; Shenui capsule high dose group, middle dose group, low dose group, positive control group, Shengui capsule middle dose group and positive drug combination group, each Group 15 only. Each group of rats was intragastrically administered once a day for 7 consecutive days, 60 minutes after the last dose, 10% urethane 1100/100g intraperitoneal anesthesia, and the elevation was fixed on the operating table of the rat constant temperature (37 °C). Perform surgery. Bend the hair to the abdomen, cut the abdominal skin in the middle, and bluntly peel off the rectus abdominis and enter the abdominal cavity. A small iron micro-pressure spring was implanted in the direction of the renal vein in the caudal iliac vein of the tail vein to suppress hemostasis. Close the abdominal cavity. After 2 hours, open the abdominal cavity, take out the stainless iron micro-pressure spring and the thrombus together, wash gently with physiological saline, and absorb excess water. The compression spring and the thrombus were placed in 2 ml of an alkaline sodium carbonate solution (100 mmol/L sodium hydroxide, 2% sodium carbonate), and placed in a boiling water bath for 3 min. The protein content in the 100 μ ΐ sample was determined by the Coomassie brilliant blue method (Bradford method).
2. 3考马斯亮兰法 (Bradford法) 测定蛋白浓度: 2. 3 Coomassie Brilliant Method (Bradford Method) Determination of protein concentration:
2. 3. 1试剂: (1)标准蛋白质溶液, 用牛血清清蛋白(BSA), 配制成 L 0mg/ml和 0. lmg/ml的标准蛋白质溶液。 (2)考马斯亮兰 G-250染料试剂: 称 lOOmg考马斯 亮兰 G-250, 溶于 95%乙醇 50ml后, 再加入 120ml 85%的磷酸, 用水稀释至 1升。 2. 3. 2标准曲线制作及未知样品测量方法 2. 3. 1 Reagents: (1) Standard protein solution, prepared with bovine serum albumin (BSA), a standard protein solution of L 0 mg/ml and 0.1 mg/ml. (2) Coomassie brilliant blue G-250 dye reagent: Weigh lOOmg Coomassie brilliant blue G-250, dissolved in 95% ethanol 50ml, then add 120ml of 85% phosphoric acid, diluted to 1 liter with water. 2. 3. 2 standard curve production and unknown sample measurement methods
(1)按需取试管, 分为两组。一组用 1. 0mg/ml的标准蛋白质溶液给各试管分别加 Λ: 0 (作空白) 、 0. 005、 0. 01、 0. 02、 0. 03、 0. 04、 0. 05ml , 然后用无离子水 补充到 0. 05ml。 其余留作未知样品。 每支试管 0. 05ml样本液。 最后各试管中分 别加入 2. 5ml考马斯亮兰 G-250试剂, 每加完一管, 立即在旋涡混合器上混合。 (1) Take the test tubes as needed and divide them into two groups. A set of standard protein solutions with 1.0 mg/ml were added to each tube: 0 (for blank), 0. 005, 0. 01, 0. 02, 0. 03, 0. 04, 0. 05ml, then 0毫升。 Adding with 0. 05ml. The rest is left as an unknown sample. 0. 05ml sample solution per tube. Finally, add 2. 5 ml of Coomassie Brilliant G-250 Reagent to each tube and mix immediately on the vortex mixer after each tube.
(2)加完试剂 5分钟后, 以空白管调零, 在分光光度计上测定各样品在 595nm处 的光吸收值 (A595) 。 (3)用标准蛋白质量 (mg)为横座标, 用吸光度值 A595为纵座 标, 作图, 即得到一条标准曲线。 由此标准曲线, 根据测出的未知样品的 A595值, 查出未知样品的蛋白质含量。 (2) After the reagent was added for 5 minutes, the blank tube was adjusted to zero, and the light absorption value (A 595 ) of each sample at 595 nm was measured on a spectrophotometer. (3) Using the standard protein amount (mg) as the abscissa, and using the absorbance value A 595 as the ordinate, plotting, that is, a standard curve is obtained. From this standard curve, the protein content of the unknown sample is detected based on the measured A 595 value of the unknown sample.
2. 4统计分析: 数据以血栓蛋白含量的平均值士标准差表示血栓形成的程度, 蛋 白含量高者血栓形成程度高。 统计学显著性用 t检验进行组间比较。 2. 4 Statistical analysis: The data indicates the degree of thrombosis by the standard deviation of the mean value of thrombus protein content, and the degree of thrombosis is high in patients with high protein content. Statistical significance was compared between groups using the t test.
3.实验结果 3. Experimental results
3. 1蛋白标准曲线 如图 1。 图中可见, 蛋白含量从 0. 01mg/ml至 L 0mg/ml呈 S 形曲线:蛋白含量从 0. 01mg/ml至 0. lmg/ml,其吸光度值的升高较缓;从 0. lmg/ml 至 0. 6mg/ml , 吸光度值升高很快; 从 0. 6mg/ml至 1. Omg/ml的吸光度值升高又
趋缓。 由于正常动物血栓中的蛋白含量较高, 而药物抑制血栓形成动物的血栓蛋 白含量较低, 因此, 在实际测定蛋白含量时分别需要高、低两种浓度的标准蛋白 液对照管。 3. 1 protein standard curve is shown in Figure 1. The phage value is 0. lmg. /ml to 0. 6mg / ml, the absorbance value rises quickly; from 0. 6mg / ml to 1. Omg / ml absorbance value rises again Slow down. Because the protein content in the normal animal thrombus is higher, and the drug inhibits the thrombus protein content of the thrombotic animal, the standard protein liquid control tube of the high and low concentrations is required for the actual determination of the protein content.
3. 2血栓蛋白测定结果参见图 2.。统计学 t检验结果表明,所有用药组包括阳性 药组、 实验用药高、 中、 低剂量组与未用药 (空白) 组比较差异均非常显著 (P <0. 01 ), 说明参桂胶囊具有显著的抑制血栓形成作用。但用药组之间差异不显 著, 说明参桂胶囊高、 中、 低剂量均已达到其最大作用强度。 用药组中的 "参阿 组"是参桂胶囊与阿司匹林联合用药组, 其抗血栓作用与单独应用阿司匹林组, 或参桂胶囊高、 中、低剂量组均无显著差异, 说明参桂胶囊与阿司匹林之间无明 显的协同作用, 且均已达到其最大作用强度。 3. 2 The results of thrombus protein assay are shown in Figure 2. The results of statistical t-test showed that all the drug-treated groups including the positive drug group, the experimental drug high, medium and low dose groups and the unmedicated (blank) group were significantly different (P <0.01), indicating that the Shengui capsule has significant The inhibition of thrombosis. However, the difference between the medication groups was not significant, indicating that the high, medium and low doses of Shenui Capsule had reached their maximum intensity. The "Shen A group" in the medication group was the combination of Shenui Capsule and Aspirin. The antithrombotic effect was not significantly different from the aspirin group alone or the high, medium and low dose groups of Shenui Capsule. There is no significant synergy between aspirin and it has reached its maximum intensity of action.
4.讨论 4. Discussion
中医认为冠心病心绞痛属于胸痹范畴, 其发病源于上焦阳气微而阴寒盛。 《金匮 要略 ·胸痹心痛短气病脉证治第九》篇曰: "夫脉当取太过不及, 阳微阴弦。 即 胸痹而痛。 所以然者, 责其极虚也。 今日虚阳上焦, 所以胸痹心痛者, 以其阴弦 故也"。 参桂胶囊中红参益气, 桂枝温阳, 川芎通脉因而用于具有心阳不振, 气 虚血瘀的胸痹可以获得较好的疗效。相关文献报道的药理研究多涉及心功能不全 的机理研究, 如参桂胶囊治疗心功能不全的作用机制与其干预心肌重构、抑制心 肌细胞凋亡的作用有关,也与其降低血浆内皮素 (ET) 、血管紧张素 i Arig ll ) 水 平等作用有关。但根据中药药理的研究结果,参桂胶囊组成药物的作用绝不仅此 而已。 Chinese medicine believes that angina pectoris is a category of chest sputum, and its pathogenesis stems from the slight suffocation of the upper Jiaoyang. "Golden 匮 · · 痹 痹 痹 痹 痹 短 短 短 短 短 短 短 短 短 》 》 》 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰The imaginary yang is on the coke, so the chest is heartache, and the sinus is also ". In the Shenui Capsule, the red ginseng and the qi, the Guizhi Wenyang, and the Chuanxiong Tongmai are used for the chest sputum with yang deficiency and qi deficiency and blood stasis. Pharmacological studies reported in related literature mostly involve the mechanism of cardiac dysfunction. For example, the mechanism of action of Shengui Capsule in treating cardiac dysfunction is related to its intervention in myocardial remodeling and inhibition of cardiomyocyte apoptosis, and it also reduces plasma endothelin (ET). , angiotensin i Arig ll) level and other effects. However, according to the research results of traditional Chinese medicine pharmacology, the role of Shengui Capsules in forming drugs is not limited to this.
现代药理研究证明, 人参二醇组 50mg/kg、 70mg/kg家兔静脉注射有抑制血小板 聚集的作用。人参根剂量 60mg/kg可明显抑制血瘀大鼠的血栓形成。许多研究肯 定了人参或人参皂甙对血小板聚集的抑制作用,并认为其作用机制与提高血小板 内 cAMPCa++拮抗以及阻滞 PG代谢(抑制环氧合酶和 TXA2合成酶,减少 TXA2、PGA2 生成)等作用有关。桂枝注射液腹腔注射能解除兔实验性肢体痹症模型红细胞和 血小板聚集, 改善组织的血液循环。桂皮醛在体外对血小板聚集有抑制作用。 川 芎和川芎嗉在体外对由 ADP、胶原和凝血酶诱导的家兔和人血小板聚集有显著的 抑制作用,并使已聚集的血小板迅速解聚。川芎嗉在体内可抑制过敏性哮喘豚鼠、 败血症家兔的血小板聚集。心脑血管患者服用川芎嗉后可使红细胞和血小板表面
电荷增加,聚集性降低。川芎嗉抑制血小板聚集的机制可能与抑制胞内 Ca++释放、 影响 TXA2/PGI2之间平衡、 置换血小板膜 Ca++使膜负电荷增加等作用有关, 还可 能与 (川芎哚和川芎注射液) 提高 (小鼠血浆和兔血小板悬液) cAMP 水平的作 用有关。 Modern pharmacological studies have shown that intravenous injection of 50mg/kg and 70mg/kg rabbits in the panaxadiol group inhibits platelet aggregation. The ginseng root dose of 60 mg/kg can significantly inhibit the thrombosis of blood stasis rats. Many studies have confirmed the inhibitory effect of ginseng or ginseng saponin on platelet aggregation, and believe that its mechanism of action and increase platelet cAMPCa ++ antagonism and block PG metabolism (inhibition of cyclooxygenase and TXA2 synthetase, reduce TXA2, PGA2 production) Related to the role. Intraperitoneal injection of Guizhi injection can relieve red blood cell and platelet aggregation in rabbit experimental limb snoring model and improve tissue blood circulation. Cinnamaldehyde inhibits platelet aggregation in vitro. Chuanxiong and Chuanxiong have significant inhibitory effects on rabbit and human platelet aggregation induced by ADP, collagen and thrombin in vitro, and rapidly disaggregate the aggregated platelets. Chuanxiong can inhibit platelet aggregation in allergic asthma guinea pigs and sepsis rabbits. Cardiovascular and cerebrovascular patients can take red blood cells and platelet surface after taking Chuanxiong The charge increases and the aggregation decreases. The mechanism by which Chuanxiong inhibits platelet aggregation may be related to inhibition of intracellular Ca ++ release, affecting the balance between TXA2/PGI2, and replacement of platelet membrane Ca ++ to increase membrane negative charge, and may also be related to (Chuangchuan and Chuanxiong injections). ) Increased (mouse plasma and rabbit platelet suspension) effects on cAMP levels.
本次试验结果表明, 三者组方, 依然能显著抑制血栓形成。 并且, 其最大抑制血 栓形成的作用与阿司匹林临床常用量的作用等同, 因此, 临床应用时可考虑单独 使用参桂胶囊进行抗栓治疗。另外,参桂胶囊与阿司匹林联合用药也未见明显的 协同增强作用,表明其与阿司匹林合用时亦无过度抑制血小板聚集功能带来的安 全性隐患。 阿司匹林是临床常用的预防血栓形成的药物, 因此, 临床实际应用时 如果病人在服用参桂胶囊的同时服用预防血栓形成的阿司匹林常用量同样是安 全的。 The results of this trial showed that the three groups can still significantly inhibit thrombosis. Moreover, its maximum inhibitory effect on thrombus formation is equivalent to the usual clinical dose of aspirin. Therefore, it is advisable to use Shengui capsule alone for antithrombotic therapy in clinical application. In addition, there was no obvious synergistic enhancement effect between Shengui Capsule and aspirin, indicating that it did not inhibit the safety hazard caused by platelet aggregation function when combined with aspirin. Aspirin is a commonly used drug for preventing thrombosis in clinical practice. Therefore, if the patient takes the Shengui capsule while taking the aspirin for preventing thrombosis, the usual amount is also safe.
参桂胶囊通过抑制血管内血栓形成, 阻止血管病变发展中的一些病理环节, 不仅 可以从根本上改善心脏冠脉供血, 而且还可以用于周围血管及脑血管疾病的防 治。 By inhibiting the formation of intravascular thrombus and preventing some pathological links in the development of vascular lesions, Shenui Capsule can not only improve the coronary blood supply of the heart, but also can be used for the prevention of peripheral blood vessels and cerebrovascular diseases.
参考文献: references:
[ 1] 殷惠军, 蒋跃绒, 刘颖, 王承龙, 郭艳, 参桂胶囊对大鼠心肌梗死后心功能 影响的研究, 上海医药 [J] , 2005, 26 ( 10 ) : 447-448。 [1] Yin Huijun, Jiang Yuerong, Liu Ying, Wang Chenglong, Guo Yan, Study on the effect of Shengui Capsule on cardiac function after myocardial infarction in rats, Shanghai Medical Journal [J] , 2005, 26 ( 10 ) : 447-448.
[2] 李宗铎, 李文超, 李文权, 董玉秀, 参桂胶囊对犬心脏血流动力学的作用, 河南中医学院学报 [J], 2003, 18 ( 2 ) : 22-28。 [2] Li Zongxi, Li Wenchao, Li Wenquan, Dong Yuxiu, The effect of Shengui Capsule on hemodynamics in dogs, Journal of Henan College of Traditional Chinese Medicine [J], 2003, 18 ( 2 ) : 22-28.
[3] 李宗铎, 索润堂, 参桂胶囊药理学研究, 北京中医药大学学报 [J] , 2003, 26 (4) : 56-58。 [3] Li Zongqi, Su Runtang, Pharmacological Research of Shenui Capsule, Journal of Beijing University of Traditional Chinese Medicine [J] , 2003, 26 (4) : 56-58.
[4] 耿秀双, 李云富, 党彦平, 参桂胶囊辅助治疗重度充血性心力衰竭的临床疗 效观察, 中国药房 [J], 2008, 19 ( 30 ) : 2391-2392。 [4] Yan Xiushuang, Li Yunfu, Dang Yanping, Shen Gui Capsule for the treatment of severe congestive heart failure: Chinese pharmacy [J], 2008, 19 ( 30 ) : 2391-2392.
[5] 刘咏听, 孙芳毅, 参桂胶囊治疗冠心病不稳定型心绞痛 113例, 中西医结合 心脑血管病杂志 [J], 2007, 5 ( 9 ) : 879。 [5] Liu Yu, Sun Fangyi, Shen Gui Capsule for the treatment of 113 cases of unstable angina pectoris of coronary heart disease, Chinese and Western medicine combined with cardiovascular and cerebrovascular disease [J], 2007, 5 ( 9 ) : 879.
[6] 李争, 黄平, 张炬, 李宗铎, 黄玉秀, 参桂胶囊治疗冠心病心绞痛的临床研 究, 中国医药学报 [J], 2000, 15 ( 4) : 35-36。 [6] Li Zheng, Huang Ping, Zhang Ju, Li Zongxi, Huang Yuxiu, Shen Gui Capsule for the treatment of coronary heart disease with angina pectoris, Chinese Journal of Medicine [J], 2000, 15 (4): 35-36.
[7] Kumada T, Ishihara M, Ogawa H, Abiko Y (1980) , Experimental model of venous thrombosis in rats and effect of some agents, Thrombosis Res. , 18 :
189-203。 [7] Kumada T, Ishihara M, Ogawa H, Abiko Y (1980) , Experimental model of venous thrombosis in rats and effect of some agents, Thrombosis Res. , 18 : 189-203.
[8] Just M, Schonaf inger K (1991) , Antithrombotic prop erties of a novel sydnonimine derivative, J Cardiovasc Pharmacol 17 (suppl 3): S121-S126. [8] Just M, Schonaf inger K (1991), Antithrombotic prop erties of a novel sydnonimine derivative, J Cardiovasc Pharmacol 17 (suppl 3): S121-S126.
[9]殷惠军,蒋跃绒,刘 颖,张 颖参桂胶囊对心肌梗死后心功能不全大鼠 ET、 Ang II影响的研究, 中西医结合心脑血管病杂志, 2004, 2 ( 6 ) : 336-337。 [9] Yin Huijun, Jiang Yuerong, Liu Ying, Zhang Ying Shen Gui Capsule on the effects of ET and Ang II in rats with myocardial infarction after cardiac insufficiency, Chinese Journal of Integrated Traditional and Western Cardiology, 2007, 2 ( 6 ) : 336- 337.
[ 10] 中华本草, 上海科学技术出版社, 1999年第一版, 第 5卷: 812。 [10] Chinese Materia Medica, Shanghai Science and Technology Press, 1999, First Edition, Volume 5: 812.
[ 11] 中华本草, 上海科学技术出版社, 1999年第一版, 第 3卷: 42-43。 [11] Chinese Materia Medica, Shanghai Science and Technology Press, 1999, First Edition, Volume 3: 42-43.
[ 12] 中华本草, 上海科学技术出版社, 1999年第一版, 第 5卷: 978。 [12] Chinese Materia Medica, Shanghai Science and Technology Press, 1999, First Edition, Volume 5: 978.
附图说明: BRIEF DESCRIPTION OF THE DRAWINGS:
图 1考马斯亮蓝测定蛋白含量标准曲线 Figure 1 Coomassie brilliant blue determination of protein content standard curve
图 2血栓蛋白含量测定结果 Figure 2 Thrombus protein content determination results
具体实施方式: detailed description:
以下通过实施例进一步说明本发明, 但不作为对本发明的限制。 The invention is further illustrated by the following examples, which are not intended to limit the invention.
实施例 1 Example 1
参桂胶囊药物活性物质的制备: Preparation of medicinal substances of Shengui Capsule:
配方: Recipe:
红参 300g, 川芎 500g, 桂枝 200g Red Ginseng 300g, Chuanxiong 500g, Guizhi 200g
取红参, 粉碎成细粉, 备用; 剩余的红参粉碎成粗粉, 照流浸膏剂与浸膏剂项下 的渗漉法 (中国药典 2000年版一部附录 I 0), 用乙醇作溶剂进行渗漉, 收集渗 漉液, 备用; 川芎、桂枝加水蒸馏提取挥发油, 收集挥发油, 备用; 蒸馏液滤过, 滤液备用; 药渣与上述红参药渣加水煎煮二次, 滤过, 滤液合并, 浓缩, 放冷, 加乙醇, 放置, 滤过 , 滤液与红参渗漉液合并, 回收乙醇并浓缩至稠膏状, 加 红参细粉, 拌勾, 干燥, 粉碎成细粉。 挥发油用剩余的红参细粉吸附, 混勾, 再 与上述细粉混勾, 即得本发明的参桂胶囊药物活性物质。 实施例 2 Take red ginseng, pulverize into fine powder, spare; the remaining red ginseng is pulverized into coarse powder, and the percolation method under the extract of extract and extract (Chinese Pharmacopoeia 2000 edition, Appendix I 0), using ethanol as solvent Seepage, collect the seepage solution, reserve; Chuanxiong, Guizhi add water to extract volatile oil, collect volatile oil, reserve; distillate filtered, the filtrate is reserved; the dregs and the above red ginseng residue are decoctioned twice, filtered, filtrate Combine, concentrate, let cool, add ethanol, place, filter, and combine the filtrate with red ginseng osmosis solution, recover ethanol and concentrate to thick paste, add red ginseng powder, mix with hook, dry, pulverize into fine powder. The volatile oil is adsorbed by the remaining red ginseng fine powder, mixed and hooked, and then mixed with the above fine powder to obtain the pharmaceutically active substance of the ginseng capsule of the present invention. Example 2
胶囊剂 (参桂胶囊) 的制备, Preparation of capsules (Shengui capsules),
实施例 1的药物活性物质加入适量的淀粉, 混勾, 制成粒, 装入 1000粒胶囊, 即得。
实施例 3 The pharmaceutically active substance of Example 1 was added with an appropriate amount of starch, mixed, and granulated, and 1000 capsules were obtained. Example 3
片剂的制备, Preparation of tablets,
实施例 1的药物活性物质加入适量的淀粉, 混勾, 制成粒, 压片成 1000片, 即 得。 实施例 4 The pharmaceutically active substance of Example 1 was added with an appropriate amount of starch, mixed, and granulated, and compressed into 1000 pieces to obtain. Example 4
颗粒剂的制备, Preparation of granules,
实施例 1的药物活性物质加入适量的淀粉,蔗糖,混勾,制成 1000g,包装成 2g/ 袋, 即得。 实施例 5 The pharmaceutically active substance of Example 1 was added with an appropriate amount of starch, sucrose, and a hook to make 1000 g, and packaged into 2 g/bag, which was obtained. Example 5
药物活性物质的制备: Preparation of pharmaceutically active substances:
配方: Recipe:
红参 200g, 川芎 250g, 桂枝 100g Red Ginseng 200g, Chuanxiong 250g, Guizhi 100g
取红参, 粉碎成细粉, 备用; 剩余的红参粉碎成粗粉, 照流浸膏剂与浸膏剂项下 的渗漉法 (中国药典 2000年版一部附录 I 0), 用乙醇作溶剂进行渗漉, 收集渗 漉液, 备用; 川芎、桂枝加水蒸馏提取挥发油, 收集挥发油, 备用; 蒸馏液滤过, 滤液备用; 药渣与上述红参药渣加水煎煮二次, 滤过, 滤液合并, 浓缩, 放冷, 加乙醇, 放置, 滤过 , 滤液与红参渗漉液合并, 回收乙醇并浓缩至稠膏状, 加 红参细粉, 拌勾, 干燥, 粉碎成细粉。 挥发油用剩余的红参细粉吸附, 混勾, 再 与上述细粉混勾, 即得本发明的药物活性物质。 实施例 6 Take red ginseng, pulverize into fine powder, spare; the remaining red ginseng is pulverized into coarse powder, and the percolation method under the extract of extract and extract (Chinese Pharmacopoeia 2000 edition, Appendix I 0), using ethanol as solvent Seepage, collect the seepage solution, reserve; Chuanxiong, Guizhi add water to extract volatile oil, collect volatile oil, reserve; distillate filtered, the filtrate is reserved; the dregs and the above red ginseng residue are decoctioned twice, filtered, filtrate Combine, concentrate, let cool, add ethanol, place, filter, and combine the filtrate with red ginseng osmosis solution, recover ethanol and concentrate to thick paste, add red ginseng powder, mix with hook, dry, pulverize into fine powder. The volatile oil is adsorbed by the remaining red ginseng fine powder, mixed and hooked, and then mixed with the above fine powder to obtain the pharmaceutically active substance of the present invention. Example 6
药物活性物质的制备: Preparation of pharmaceutically active substances:
配方: Recipe:
红参 400g, 川芎 750g, 桂枝 300g Red Ginseng 400g, Chuanxiong 750g, Guizhi 300g
取红参, 粉碎成细粉, 备用; 剩余的红参粉碎成粗粉, 照流浸膏剂与浸膏剂项下 的渗漉法 (中国药典 2000年版一部附录 I 0), 用乙醇作溶剂进行渗漉, 收集渗 漉液, 备用; 川芎、桂枝加水蒸馏提取挥发油, 收集挥发油, 备用; 蒸馏液滤过,
滤液备用; 药渣与上述红参药渣加水煎煮二次, 滤过, 滤液合并, 浓缩, 放冷, 加乙醇, 放置, 滤过 , 滤液与红参渗漉液合并, 回收乙醇并浓缩至稠膏状, 加 红参细粉, 拌勾, 干燥, 粉碎成细粉。 挥发油用剩余的红参细粉吸附, 混匀, 再 与上述细粉混匀, 即得本发明的药物活性物质。
Take red ginseng, pulverize into fine powder, spare; the remaining red ginseng is pulverized into coarse powder, and the percolation method under the extract of extract and extract (Chinese Pharmacopoeia 2000 edition, Appendix I 0), using ethanol as solvent Seepage, collecting percolate, and standby; extracting volatile oil from Chuanxiong and Guizhi by adding water, collecting volatile oil, and storing; distillate filtered, The filtrate is reserved; the dregs and the above red ginseng slag are boiled twice with water, filtered, the filtrate is combined, concentrated, allowed to cool, added with ethanol, placed, filtered, and the filtrate is combined with the red ginseng osmosis solution, and the ethanol is recovered and concentrated. Thick paste, add red ginseng powder, mix with hook, dry, pulverize into fine powder. The volatile oil is adsorbed by the remaining red ginseng fine powder, mixed, and then mixed with the above fine powder to obtain the pharmaceutically active substance of the present invention.
Claims
1、 用中药红参, 川芎, 桂枝制备的药物制剂在制备抗血栓的药物中的应用。1. Application of pharmaceutical preparations prepared from traditional Chinese medicines red ginseng, chuanxiong and cassia twig in the preparation of anti-thrombotic drugs.
2、 根据权利要求 1的应用, 其特征在于, 所述应用是抑制血栓的形成。 2. The application according to claim 1, characterized in that the application is to inhibit the formation of thrombus.
3、 根据权利要求 1的应用, 其特征在于, 所述应用是用于周围血管及脑血管疾 病的防治。 3. The application according to claim 1, characterized in that the application is used for the prevention and treatment of peripheral vascular and cerebrovascular diseases.
4、 根据权利要求 1的应用, 其特征在于, 所述应用是治疗脑梗塞。 4. The application according to claim 1, characterized in that the application is for the treatment of cerebral infarction.
5、 根据权利要求 1的应用, 其特征在于, 所述应用是改善心脏冠脉供血。 5. The application according to claim 1, characterized in that the application is to improve the coronary blood supply of the heart.
6、 根据权利要求 1的应用, 其特征在于, 所述应用是治疗心肌梗塞。 6. The application according to claim 1, characterized in that the application is for the treatment of myocardial infarction.
7、 根据权利要求 1的应用, 其特征在于, 所述药物其配方组成如下: 红参 l-1000g, 川芎 l-1000g, 桂枝 l-1000go 7. Application according to claim 1, characterized in that the formula of the medicine is as follows: red ginseng 1-1000g, Ligusticum chuanxiong 1-1000g, cassia twig 1-1000go
8、 根据权利要求 1的应用, 其特征在于, 所述药物其配方组成如下: 红参 200- 400g, 川芎 250_750g, 桂枝 100_300g。 8. Application according to claim 1, characterized in that the formula of the medicine is as follows: red ginseng 200-400g, Ligusticum chuanxiong 250-750g, cassia twig 100-300g.
9、 根据权利要求 1的应用, 其特征在于, 所述药物其配方组成如下: 红参 300g, 川芎 500g, 桂枝 200g。 9. Application according to claim 1, characterized in that the formula of the medicine is as follows: 300g red ginseng, 500g chuanxiong, and 200g cassia twig.
10、 根据权利要求 1的应用, 其特征在于, 所述药物制备方法如下: 10. Application according to claim 1, characterized in that the pharmaceutical preparation method is as follows:
红参 300g, 川芎 500g, 桂枝 200g Red ginseng 300g, Chuanxiong 500g, Guizhi 200g
取红参, 粉碎成细粉, 备用; 剩余的红参粉碎成粗粉, 照中国药典 2000年版一 部附录 1 0流浸膏剂与浸膏剂项下的渗漉法, 用乙醇作溶剂进行渗漉, 收集渗漉 液, 备用; 川芎、 桂枝加水蒸馏提取挥发油, 收集挥发油, 备用; 蒸馏液滤过, 滤液备用; 药渣与上述红参药渣加水煎煮二次, 滤过, 滤液合并, 浓缩, 放冷, 加乙醇, 放置, 滤过 , 滤液与红参渗漉液合并, 回收乙醇并浓缩至稠膏状, 加 红参细粉, 拌勾, 干燥, 粉碎成细粉。 挥发油用剩余的红参细粉吸附, 混勾, 再 与上述细粉混勾, 加入适量的淀粉, 混勾, 装入胶囊, 制成粒, 即得。
Take the red ginseng and crush it into fine powder and set aside; crush the remaining red ginseng into coarse powder and follow the percolation method under Appendix 10 of the Chinese Pharmacopoeia 2000 edition, using ethanol as the solvent. , collect the leachate, and set it aside; add water to distill Ligusticum Chuanxiong and Guizhi to extract the volatile oil, collect the volatile oil, and set it aside; filter the distillate, and set the filtrate for set use; decoct the medicinal residue and the above-mentioned red ginseng medicinal residue twice with water, filter, and combine the filtrate. Concentrate, let cool, add ethanol, let stand, filter, combine the filtrate and red ginseng leachate, recover the ethanol and concentrate to a thick paste, add red ginseng fine powder, mix, dry and pulverize into fine powder. The volatile oil is adsorbed with the remaining fine red ginseng powder, mixed, then mixed with the above fine powder, added with an appropriate amount of starch, mixed, put into capsules, and granulated to obtain.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210258148.6A CN102846711B (en) | 2012-07-24 | 2012-07-24 | 'Shen Gui ' capsule is preparing the application in antithrombotic reagent |
CN201210258148.6 | 2012-07-24 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2014015507A1 true WO2014015507A1 (en) | 2014-01-30 |
Family
ID=47393956
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2012/079235 WO2014015507A1 (en) | 2012-07-24 | 2012-07-27 | Application of shengui capsule in preparing antithrombotic drugs |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN102846711B (en) |
WO (1) | WO2014015507A1 (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105616857A (en) * | 2016-01-28 | 2016-06-01 | 胶州市人民中医医院 | Traditional Chinese medicine composition for treating gout and preparation method thereof |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1961924A (en) * | 2006-11-09 | 2007-05-16 | 上海玉丹药业有限公司 | Treatment of cardiac insufficiency and cardiac failure by using 'Shen Gui' capsule |
-
2012
- 2012-07-24 CN CN201210258148.6A patent/CN102846711B/en active Active
- 2012-07-27 WO PCT/CN2012/079235 patent/WO2014015507A1/en active Application Filing
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1961924A (en) * | 2006-11-09 | 2007-05-16 | 上海玉丹药业有限公司 | Treatment of cardiac insufficiency and cardiac failure by using 'Shen Gui' capsule |
Non-Patent Citations (1)
Title |
---|
DENG, XIANGTAO ET AL.: "Content Determination of Ferulic Acid in Shengui Capsules", JOURNAL OF HENAN UNIVERSITY OF CHINESE MEDICINE, vol. 22, no. 1, 31 January 2007 (2007-01-31), pages 47 * |
Also Published As
Publication number | Publication date |
---|---|
CN102846711A (en) | 2013-01-02 |
CN102846711B (en) | 2015-12-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7973014B2 (en) | Medicinal composition containing ginseng secondary glycosides, its preparation method and application | |
CN101585859B (en) | Novel scutellarin derivative as well as preparation method and pharmaceutical composition thereof | |
CN103006838A (en) | Traditional Chinese medicine composition for treating cardiovascular and cerebrovascular diseases | |
CN101099753A (en) | Preparation method and application for general saponin of cortex ilecis rotundae | |
CN100386071C (en) | Medicine for treating cough and chronic bronchitis | |
CN103006769A (en) | Traditional Chinese medicine composition for treating cardiovascular and cerebrovascular diseases and preparation method thereof | |
CN104027428B (en) | Preparation method of traditional Chinese medicine compound and application of traditional Chinese medicine compound in prevention and treatment of senile dementia | |
CN102716135B (en) | Lupenone prevents in preparation or treats the application in the product of diabetes | |
CN104435045B (en) | A kind of Chinese medicine composition for treating apoplexy and its sequelae and preparation method thereof | |
CN102048841B (en) | Lactogenic traditional Chinese medicine composition and preparation method thereof | |
CN104138376A (en) | A sustained release agent improving anoxia endurance | |
WO2014015507A1 (en) | Application of shengui capsule in preparing antithrombotic drugs | |
CN102228535A (en) | Application of total saponins and total flavones in preparation of drugs for treating cardiovascular diseases | |
CN101585860A (en) | 4',5,6-trimethoxy scutellarin as well as preparation method and pharmaceutical composition thereof | |
WO2009076869A1 (en) | Salvianolic acid of high purity, preparation method and use thereof | |
CN101032534B (en) | Method of preparing Ilex rotunda Thunb total saponins and the application thereof | |
CN101152223B (en) | Use of poplar leaf phenols extract in preparation of medicine for treating cardiovascular disease | |
CN103784683B (en) | A kind of Chinese medicine composition treating obesity and its preparation method and application | |
ZA200603160B (en) | Use of agomelatine in obtaining medicaments intended for the treatment of bipolar disorders | |
CN101176769B (en) | Pharmaceutical composition of cattail pollen and red orpin | |
CN102552398A (en) | Medicinal composition of radix salviae miltiorrhizae extract and application thereof | |
WO2017219453A1 (en) | Valsartan dispersible tablet and preparation method thereof | |
JPS5938204B2 (en) | Aplastic anemia treatment agent | |
CN103405442A (en) | Pharmaceutical composition of salvia miltiorrhiza extractive, and use thereof | |
CN102258600A (en) | Medicine composition for treating cardiovascular disease |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 12881553 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 12881553 Country of ref document: EP Kind code of ref document: A1 |