CN101176751B - Pharmaceutical composition of red sage root and cassia twig - Google Patents
Pharmaceutical composition of red sage root and cassia twig Download PDFInfo
- Publication number
- CN101176751B CN101176751B CN2006100700521A CN200610070052A CN101176751B CN 101176751 B CN101176751 B CN 101176751B CN 2006100700521 A CN2006100700521 A CN 2006100700521A CN 200610070052 A CN200610070052 A CN 200610070052A CN 101176751 B CN101176751 B CN 101176751B
- Authority
- CN
- China
- Prior art keywords
- extract
- radix salviae
- ramulus cinnamomi
- pharmaceutical composition
- salviae miltiorrhizae
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 40
- 244000037364 Cinnamomum aromaticum Species 0.000 title abstract description 6
- 235000014489 Cinnamomum aromaticum Nutrition 0.000 title abstract description 6
- 240000007164 Salvia officinalis Species 0.000 title description 5
- 235000005412 red sage Nutrition 0.000 title description 3
- 239000000284 extract Substances 0.000 claims abstract description 151
- 239000003814 drug Substances 0.000 claims abstract description 85
- 229940079593 drug Drugs 0.000 claims abstract description 67
- 238000002360 preparation method Methods 0.000 claims abstract description 48
- 238000002347 injection Methods 0.000 claims abstract description 33
- 239000007924 injection Substances 0.000 claims abstract description 33
- 239000000203 mixture Substances 0.000 claims abstract description 28
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 17
- 230000002526 effect on cardiovascular system Effects 0.000 claims abstract description 17
- 238000009472 formulation Methods 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 37
- 230000008569 process Effects 0.000 claims description 18
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 16
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 claims description 11
- AXMVYSVVTMKQSL-UHFFFAOYSA-N UNPD142122 Natural products OC1=CC=C(C=CC=O)C=C1O AXMVYSVVTMKQSL-UHFFFAOYSA-N 0.000 claims description 11
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 claims description 11
- 229940117916 cinnamic aldehyde Drugs 0.000 claims description 11
- 239000004615 ingredient Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 7
- SNKFFCBZYFGCQN-UHFFFAOYSA-N 2-[3-[3-[1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy]carbonyl-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydro-1-benzofuran-4-yl]prop-2-enoyloxy]-3-(3,4-dihydroxyphenyl)propanoic acid Chemical compound C=1C=C(O)C=2OC(C=3C=C(O)C(O)=CC=3)C(C(=O)OC(CC=3C=C(O)C(O)=CC=3)C(O)=O)C=2C=1C=CC(=O)OC(C(=O)O)CC1=CC=C(O)C(O)=C1 SNKFFCBZYFGCQN-UHFFFAOYSA-N 0.000 claims description 6
- SNKFFCBZYFGCQN-VWUOOIFGSA-N Lithospermic acid B Natural products C([C@H](C(=O)O)OC(=O)\C=C\C=1C=2[C@H](C(=O)O[C@H](CC=3C=C(O)C(O)=CC=3)C(O)=O)[C@H](OC=2C(O)=CC=1)C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 SNKFFCBZYFGCQN-VWUOOIFGSA-N 0.000 claims description 6
- 239000000890 drug combination Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 150000007965 phenolic acids Chemical class 0.000 claims description 6
- 238000012545 processing Methods 0.000 claims description 6
- STCJJTBMWHMRCD-UHFFFAOYSA-N salvianolic acid B Natural products OC(=O)C(Cc1ccc(O)c(O)c1)OC(=O)C=Cc2cc(O)c(O)c3OC(C(C(=O)OC(Cc4ccc(O)c(O)c4)C(=O)O)c23)c5ccc(O)c(O)c5 STCJJTBMWHMRCD-UHFFFAOYSA-N 0.000 claims description 6
- 239000002552 dosage form Substances 0.000 claims description 5
- -1 phenolic acid compound Chemical class 0.000 claims description 5
- 235000009048 phenolic acids Nutrition 0.000 claims description 5
- 239000000341 volatile oil Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 3
- 230000000694 effects Effects 0.000 abstract description 25
- 208000031225 myocardial ischemia Diseases 0.000 abstract description 19
- 201000006474 Brain Ischemia Diseases 0.000 abstract description 12
- 239000002994 raw material Substances 0.000 abstract description 12
- 206010063837 Reperfusion injury Diseases 0.000 abstract description 8
- 244000132619 red sage Species 0.000 abstract description 7
- WTPPRJKFRFIQKT-UHFFFAOYSA-N 1,6-dimethyl-8,9-dihydronaphtho[1,2-g][1]benzofuran-10,11-dione;1-methyl-6-methylidene-8,9-dihydro-7h-naphtho[1,2-g][1]benzofuran-10,11-dione Chemical compound O=C1C(=O)C2=C3CCCC(=C)C3=CC=C2C2=C1C(C)=CO2.O=C1C(=O)C2=C3CCC=C(C)C3=CC=C2C2=C1C(C)=CO2 WTPPRJKFRFIQKT-UHFFFAOYSA-N 0.000 abstract description 6
- 230000008901 benefit Effects 0.000 abstract description 4
- 230000002785 anti-thrombosis Effects 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 5
- 208000018152 Cerebral disease Diseases 0.000 abstract 1
- 230000009044 synergistic interaction Effects 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- 239000000243 solution Substances 0.000 description 33
- 241000700159 Rattus Species 0.000 description 31
- 239000008187 granular material Substances 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 20
- 239000002775 capsule Substances 0.000 description 17
- 238000000605 extraction Methods 0.000 description 17
- 210000004556 brain Anatomy 0.000 description 15
- 238000005516 engineering process Methods 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 15
- 239000007864 aqueous solution Substances 0.000 description 13
- 230000017531 blood circulation Effects 0.000 description 13
- 208000028867 ischemia Diseases 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 12
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 12
- 206010061216 Infarction Diseases 0.000 description 11
- 210000001715 carotid artery Anatomy 0.000 description 11
- 230000008859 change Effects 0.000 description 11
- 210000004351 coronary vessel Anatomy 0.000 description 11
- 230000007574 infarction Effects 0.000 description 11
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 10
- 229920000881 Modified starch Polymers 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 10
- 235000019359 magnesium stearate Nutrition 0.000 description 10
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 10
- 239000008108 microcrystalline cellulose Substances 0.000 description 10
- 229940016286 microcrystalline cellulose Drugs 0.000 description 10
- 238000012856 packing Methods 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- JLTCWSBVQSZVLT-CDIPANDDSA-N (2s)-n-[(2s)-6-amino-1-[(2-amino-2-oxoethyl)amino]-1-oxohexan-2-yl]-1-[(4r,7s,10s,13s,16s,19r)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-benzyl-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosan Chemical compound NCCCC[C@@H](C(=O)NCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](N)CSSC1.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 JLTCWSBVQSZVLT-CDIPANDDSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 102000005320 Posterior Pituitary Hormones Human genes 0.000 description 9
- 108010070873 Posterior Pituitary Hormones Proteins 0.000 description 9
- 206010008118 cerebral infarction Diseases 0.000 description 9
- 229960004756 ethanol Drugs 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 206010008120 Cerebral ischaemia Diseases 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 230000002490 cerebral effect Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000013558 reference substance Substances 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 239000002671 adjuvant Substances 0.000 description 7
- 230000000302 ischemic effect Effects 0.000 description 7
- 229940023488 pill Drugs 0.000 description 7
- 239000006187 pill Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 210000002216 heart Anatomy 0.000 description 6
- 230000004217 heart function Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000011265 semifinished product Substances 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 210000003462 vein Anatomy 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 206010002091 Anaesthesia Diseases 0.000 description 5
- 241000282472 Canis lupus familiaris Species 0.000 description 5
- 208000028389 Nerve injury Diseases 0.000 description 5
- 230000037005 anaesthesia Effects 0.000 description 5
- 208000029078 coronary artery disease Diseases 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 230000008764 nerve damage Effects 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 239000007901 soft capsule Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 230000002861 ventricular Effects 0.000 description 5
- IBGBGRVKPALMCQ-UHFFFAOYSA-N 3,4-dihydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1O IBGBGRVKPALMCQ-UHFFFAOYSA-N 0.000 description 4
- YQUVCSBJEUQKSH-UHFFFAOYSA-N 3,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 4
- 229920001353 Dextrin Polymers 0.000 description 4
- 239000004375 Dextrin Substances 0.000 description 4
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 4
- 241000700157 Rattus norvegicus Species 0.000 description 4
- AIGAZQPHXLWMOJ-UHFFFAOYSA-N Tanshinone I Chemical compound C1=CC2=C(C)C=CC=C2C(C(=O)C2=O)=C1C1=C2C(C)=CO1 AIGAZQPHXLWMOJ-UHFFFAOYSA-N 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- 230000001476 alcoholic effect Effects 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 239000003146 anticoagulant agent Substances 0.000 description 4
- 230000006399 behavior Effects 0.000 description 4
- 210000004004 carotid artery internal Anatomy 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 235000019425 dextrin Nutrition 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000007928 intraperitoneal injection Substances 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical group CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000012567 medical material Substances 0.000 description 4
- 208000010125 myocardial infarction Diseases 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- 102000004420 Creatine Kinase Human genes 0.000 description 3
- 108010042126 Creatine kinase Proteins 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 229920001214 Polysorbate 60 Polymers 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 210000001168 carotid artery common Anatomy 0.000 description 3
- 238000013270 controlled release Methods 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 210000004165 myocardium Anatomy 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000007779 soft material Substances 0.000 description 3
- PAFLSMZLRSPALU-MRVPVSSYSA-N (2R)-3-(3,4-dihydroxyphenyl)lactic acid Chemical compound OC(=O)[C@H](O)CC1=CC=C(O)C(O)=C1 PAFLSMZLRSPALU-MRVPVSSYSA-N 0.000 description 2
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 2
- 201000000736 Amenorrhea Diseases 0.000 description 2
- 206010001928 Amenorrhoea Diseases 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- PAFLSMZLRSPALU-QMMMGPOBSA-N Danshensu Natural products OC(=O)[C@@H](O)CC1=CC=C(O)C(O)=C1 PAFLSMZLRSPALU-QMMMGPOBSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 208000008454 Hyperhidrosis Diseases 0.000 description 2
- 206010062717 Increased upper airway secretion Diseases 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 2
- 239000004952 Polyamide Substances 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 235000017276 Salvia Nutrition 0.000 description 2
- PAFLSMZLRSPALU-UHFFFAOYSA-N Salvianic acid A Natural products OC(=O)C(O)CC1=CC=C(O)C(O)=C1 PAFLSMZLRSPALU-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 231100000540 amenorrhea Toxicity 0.000 description 2
- 230000000702 anti-platelet effect Effects 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 239000007766 cera flava Substances 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 229960000935 dehydrated alcohol Drugs 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 208000013219 diaphoresis Diseases 0.000 description 2
- 230000003205 diastolic effect Effects 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 210000004744 fore-foot Anatomy 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229960003943 hypromellose Drugs 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 229940100688 oral solution Drugs 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 229960002275 pentobarbital sodium Drugs 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 208000026435 phlegm Diseases 0.000 description 2
- 229920002647 polyamide Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 229960003371 protocatechualdehyde Drugs 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 239000008347 soybean phospholipid Substances 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 229940013618 stevioside Drugs 0.000 description 2
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 2
- 235000019202 steviosides Nutrition 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- OOCCDEMITAIZTP-QPJJXVBHSA-N (E)-cinnamyl alcohol Chemical compound OC\C=C\C1=CC=CC=C1 OOCCDEMITAIZTP-QPJJXVBHSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 description 1
- YMGFTDKNIWPMGF-AGYDPFETSA-N 3-(3,4-dihydroxyphenyl)-2-[(e)-3-[2-[(e)-2-(3,4-dihydroxyphenyl)ethenyl]-3,4-dihydroxyphenyl]prop-2-enoyl]oxypropanoic acid Chemical compound C=1C=C(O)C(O)=C(\C=C\C=2C=C(O)C(O)=CC=2)C=1/C=C/C(=O)OC(C(=O)O)CC1=CC=C(O)C(O)=C1 YMGFTDKNIWPMGF-AGYDPFETSA-N 0.000 description 1
- ZGZLYKUHYXFIIO-UHFFFAOYSA-N 5-nitro-2h-tetrazole Chemical compound [O-][N+](=O)C=1N=NNN=1 ZGZLYKUHYXFIIO-UHFFFAOYSA-N 0.000 description 1
- XDUXBBDRILEIEZ-UHFFFAOYSA-N 6-(hydroxymethyl)-1,6-dimethyl-8,9-dihydro-7h-naphtho[1,2-g][1]benzofuran-10,11-dione Chemical compound O=C1C(=O)C2=C3CCCC(C)(CO)C3=CC=C2C2=C1C(C)=CO2 XDUXBBDRILEIEZ-UHFFFAOYSA-N 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 244000080208 Canella winterana Species 0.000 description 1
- 235000008499 Canella winterana Nutrition 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 235000021511 Cinnamomum cassia Nutrition 0.000 description 1
- 201000006306 Cor pulmonale Diseases 0.000 description 1
- GVKKJJOMQCNPGB-JTQLQIEISA-N Cryptotanshinone Chemical compound O=C1C(=O)C2=C3CCCC(C)(C)C3=CC=C2C2=C1[C@@H](C)CO2 GVKKJJOMQCNPGB-JTQLQIEISA-N 0.000 description 1
- GVKKJJOMQCNPGB-UHFFFAOYSA-N Cryptotanshinone Natural products O=C1C(=O)C2=C3CCCC(C)(C)C3=CC=C2C2=C1C(C)CO2 GVKKJJOMQCNPGB-UHFFFAOYSA-N 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- 206010013954 Dysphoria Diseases 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010070511 Hypoxic-ischaemic encephalopathy Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 208000019255 Menstrual disease Diseases 0.000 description 1
- FVNMAWQFIILJGS-UHFFFAOYSA-N O.OC.CC#N.OC=O Chemical compound O.OC.CC#N.OC=O FVNMAWQFIILJGS-UHFFFAOYSA-N 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 208000004186 Pulmonary Heart Disease Diseases 0.000 description 1
- 206010062104 Renal mass Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 235000011135 Salvia miltiorrhiza Nutrition 0.000 description 1
- YMGFTDKNIWPMGF-QHCPKHFHSA-N Salvianolic acid A Natural products OC(=O)[C@H](Cc1ccc(O)c(O)c1)OC(=O)C=Cc2ccc(O)c(O)c2C=Cc3ccc(O)c(O)c3 YMGFTDKNIWPMGF-QHCPKHFHSA-N 0.000 description 1
- GCJWPRRNLSHTRY-VURDRKPISA-N Salvianolic acid C Chemical compound C([C@H](C(=O)O)OC(=O)\C=C\C=1C=2C=C(OC=2C(O)=CC=1)C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 GCJWPRRNLSHTRY-VURDRKPISA-N 0.000 description 1
- GCJWPRRNLSHTRY-UHFFFAOYSA-N Salvianolic acid C Natural products C=1C=C(O)C=2OC(C=3C=C(O)C(O)=CC=3)=CC=2C=1C=CC(=O)OC(C(=O)O)CC1=CC=C(O)C(O)=C1 GCJWPRRNLSHTRY-UHFFFAOYSA-N 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 229930183118 Tanshinone Natural products 0.000 description 1
- 241000053227 Themus Species 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 208000031975 Yang Deficiency Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000003916 acid precipitation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- OOCCDEMITAIZTP-UHFFFAOYSA-N allylic benzylic alcohol Natural products OCC=CC1=CC=CC=C1 OOCCDEMITAIZTP-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000002551 anterior cerebral artery Anatomy 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 229940046011 buccal tablet Drugs 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 230000001964 calcium overload Effects 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 210000000269 carotid artery external Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 1
- 229960000956 coumarin Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000005262 decarbonization Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 239000008563 guizhi decoction Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
- 229960001008 heparin sodium Drugs 0.000 description 1
- 206010019847 hepatosplenomegaly Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000010112 ling-gui-zhu-gan decoction Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 210000003657 middle cerebral artery Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- PMOWTIHVNWZYFI-UHFFFAOYSA-N o-Coumaric acid Natural products OC(=O)C=CC1=CC=CC=C1O PMOWTIHVNWZYFI-UHFFFAOYSA-N 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000003119 painkilling effect Effects 0.000 description 1
- 238000005325 percolation Methods 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000001047 pyretic effect Effects 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 238000009287 sand filtration Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 229940098466 sublingual tablet Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 210000000106 sweat gland Anatomy 0.000 description 1
- 238000011003 system suitability test Methods 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000003673 urethanes Chemical class 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Abstract
The invention discloses a drug compound of danshen root or the extract and cassia twig or the extract and the preparation method, the application of preparing drugs used for cardiovascular and cerebral diseases and the formulation containing the drug compound, belonging to the medical technical field. Measured by weight, the raw material drugs for preparing the effective components in the drug compound are as follow: 200 to 5000 for danshen root, 100 to 2000 for cassia twig; or 3 to 100 for the extract of the danshen root and 1 to 30 for the extract of cassia twig. The drug compound can be made into any acceptable clinical or pharmaceutical formulation; formulation for oral use or injection is preferred. The invention has the advantages that: the two drugs in the compound have the synergistic interaction function and jointly play the role of anti-myocardial ischemia, anti-thrombosis and resisting brain ischemia reperfusion injury, thereby the treating effect is improved greatly compared to singly using danshen root or the extract and cassia twig or the extract.
Description
[technical field]
The present invention relates to pharmaceutical composition of Radix Salviae Miltiorrhizae or its extract and Ramulus Cinnamomi or its extract and preparation method thereof, the application in the medicine of preparation treatment cardiovascular and cerebrovascular disease and contain the preparation of this pharmaceutical composition, belong to medical technical field.
[background technology]
Cardiovascular and cerebrovascular disease comprises coronary heart disease, angina pectoris, myocardial infarction, blood stasis type pulmonary heart disease, ischemic encephalopathy, cerebral thrombosis, hypertension, hyperlipidemia etc.The main pathogenic factor of these diseases is that arteriosclerosis causes luminal stenosis, pipeline obstruction, thereby causes cerebral ischemia, causes that head is heavy, dizziness, headache, symptom such as uncomfortable in chest, and severe patient can cause the generation of apoplexy and myocardial infarction.Influence energy metabolism behind the cardiac-cerebral ischemia, multiple variations such as the accumulation of secondary lactic acid, calcium overload, radical damage.Cardiovascular and cerebrovascular disease all is the formidable enemy who threatens human health all the time, seizes more than 1,200 ten thousand people's life every year, near 1/4 of the total death of population.Along with China progresses into aged society; And change along with expanding economy and life style, dietary habit; The prevalence of cardiovascular and cerebrovascular disease and mortality rate rise just year by year, according to World Health Organization's prediction, to the year two thousand twenty; Noninfectious will account for 79% of China's cause of death, and wherein cardiovascular and cerebrovascular disease will account for the first place.Therefore, how effectively to prevent and treat the great attention that cardiovascular and cerebrovascular disease also just causes people.At present, the diagnosis of cardiovascular and cerebrovascular disease and control are worldwide research focuses, also are the important contents of Chinese medical theory and clinical research.
Radix Salviae Miltiorrhizae is the dry root and rhizome of labiate Radix Salviae Miltiorrhizae Salvia miltiorrhiza Bge.Bitter in the mouth, cold nature, GUIXIN, Liver Channel.Stasis-dispelling and pain-killing is arranged, promoting blood circulation to restore menstrual flow, the effect of the relieving restlessness that clears away heart-fire.Be used for menoxenia, amenorrhea dysmenorrhea ， lumps in the chest and abdomen, breast ventral spine pain, pyretic arthralgia pain, skin infection swell and ache dysphoria and insomnia, hepatosplenomegaly, angina pectoris.
Radix Salviae Miltiorrhizae has many-sided pharmacological action: can increase coronary flow to cardiovascular system, reduce myocardial excitability and conductivity, microcirculation improvement; The formation of antiplatelet gathering and thrombosis makes blood viscosity descend antioxidation; Increase oxygen-resistant ability; Anti-inflammation improves renal function, to the cerebral tissue ischemia with in the effects such as protection of perfusion injury.The effective ingredient of Radix Salviae Miltiorrhizae can be divided into fat-soluble and water miscible, and wherein, liposoluble constituent has: Tanshinone I, tanshinone, Tanshinone II B, cryptotanshinone etc.; Water soluble ingredient has: danshensu sodium, protocatechuic acid, protocatechualdehyde, salvianolic acid A, salvianolic acid B, salvianolic acid C etc., and Radix Salviae Miltiorrhizae total phenolic acids is the effective ingredient of Radix Salviae Miltiorrhizae blood circulation promoting and blood stasis dispelling, wherein the effect of salvianolic acid B is the strongest.
Ramulus Cinnamomi is the dry twig of canella Cortex Cinnamomi Cinnamomum cassia Presl.Acrid in the mouth, sweet, warm in nature, GUIXIN, lung, urinary bladder channel.The diaphoresis expelling pathogenic factors from muscles is arranged, warming the meridian and promoting blood circulation, supporing yang activating QI, the effect of the flat gas that spins.Be used for anemofrigid cold, coldness and pain in the epigastrium, cold in blood amenorrhea, phlegm retention, edema, cardiopalmus, renal mass.
Ramulus Cinnamomi has warming and activating heart-YANG, promotes the capable effect of blood, is the indispensable medicine of treatment coronary heart disease, and is a lot of with the clinical report of Ramulus Cinnamomi compatibility treatment coronary heart disease, like Modified Pulse-Restoring Decoction, linggui zhugan decoction, Fructus Trichosanthis Bulbus Allii Macrostemonis guizhi decoction etc.Coronary heart disease is deficiency in origin and excess in superficiality card, and void then shows as the deficiency of vital energy, yang deficiency, the deficiency of YIN, and PD sudden depletion of heart-YANG usually occurs during to heart infarction, and negative and positive are from extremely; Actually not outer blood stasis, stagnation of phlegm, Ramulus Cinnamomi is role in treatment coronary heart disease, is the ability activating YANG and prormoting functioning of QI, activates yang, and subsidizes heart-yang exactly, the Wen Tongxin arteries and veins; Activating QI promptly promotes yang-energyization to give birth to, and both has been different from benefit, also is different from accent, excites the active normal operation of cardiac function.The lid heart governing blood and vessels, Ramulus Cinnamomi temperature promoting blood circulation is changed and is given birth to yang-energy, so be the key medicine of cardiopathia.
The main effective ingredient of Ramulus Cinnamomi is: cinnamic aldehyde, cinnamic acid, cinnamic alcohol, coumarin and protocatechuic acid etc.Pharmacological research shows: cinnamic aldehyde has multiple pharmacologically actives such as blood vessel dilating, coronary blood flow increasing and antiplatelet aggregation; Effects such as blood pressure lowering, blood fat reducing, heart tonifying, calmness, analgesia are arranged; Heart vigor and stimulating central nervous system system etc. can be improved, sweat gland secretion can be stimulated, the skin expansion blood vessel; Quicken the body temperature refrigeration function that scattered and disappeared through diaphoresis, curative effect is preferably being arranged aspect the cardiovascular and cerebrovascular disease treating.
Utilize the interaction of Radix Salviae Miltiorrhizae or Radix Salviae Miltiorrhizae extract and Ramulus Cinnamomi or Ramulus Cinnamomi extract at present, composition of prescription, the medicine of aspects such as preparation treatment cardiovascular and cerebrovascular disease does not appear in the newspapers as yet.
[summary of the invention]
In order to meet clinical needs; Better treat cardiovascular and cerebrovascular disease etc.; Improve the people ' s health level; The invention provides pharmaceutical composition of Radix Salviae Miltiorrhizae or its extract and Ramulus Cinnamomi or its extract and preparation method thereof, the application in the medicine of preparation treatment cardiovascular and cerebrovascular disease and contain the preparation of this pharmaceutical composition.
The crude drug of processing the contained composition and effectiveness of pharmaceutical composition of the present invention is Radix Salviae Miltiorrhizae, Ramulus Cinnamomi; Pharmaceutical composition of the present invention has significant resisting myocardial ischemia, prolongs TFT, coronary blood flow increasing; Regulate CF, reduce brain water content, dwindle ischemia side cerebral tissue infarct volume, improve the blood flow mechanics, improve the effects such as nerve injury symptom of focal brain ischemia-reperfusion injury, produced beyond thought effect.
Prove, calculate to have remarkable synergistic function in 200～5000 parts of Radix Salviae Miltiorrhizaes, 100～2000 parts of scopes of Ramulus Cinnamomi according to composition by weight through a large amount of screening experiment of inventor; Be preferably: 500～2500 parts of Radix Salviae Miltiorrhizaes, 200～1000 parts of Ramulus Cinnamomi; Further be preferably: 900～1200 parts of Radix Salviae Miltiorrhizaes, 300～600 parts of Ramulus Cinnamomi.
Radix Salviae Miltiorrhizae in the aforementioned pharmaceutical compositions and Ramulus Cinnamomi can with appropriate solvent and method be independent or mixed extraction processing obtains its extract; Total extract is processed preparation with the pharmaceutic adjuvant hybrid process again, and the main effective ingredient of gained total extract is mainly phenolic acid compound and volatile oil.Described solvent is meant solvent pharmaceutically commonly used, preferred water or alcohol, and method for distilling can extract with pharmaceutically conventional method, like decocting method, percolation, reflux extraction, continuous extraction etc.
Radix Salviae Miltiorrhizae in the aforementioned pharmaceutical compositions can be carried acid precipitation, alcohol extraction, water extract-alcohol precipitation or water through water and put forward multiple modes such as post and prepare, and the present invention has carried out preferably the extraction process of Radix Salviae Miltiorrhizae, as follows:
Get red rooted salvia, be ground into coarse powder, the decocte with water secondary adds 12 times of amounts of water for the first time, adds 10 times of amounts of water for the second time; Each 2 hours, collecting decoction filtered, and filtrate decompression is concentrated into the concentrated solution of relative density 1.10～1.15 (60 ℃); Add ethanol and reach 85% to containing the alcohol amount, cold preservation 24 hours filters, and filtrate recycling ethanol is to there not being the alcohol flavor; Add hydrochloric acid adjust pH to 2, extract 3 times, merge ethyl acetate liquid, evaporate to dryness with the ethyl acetate jolting.Residue adds the sour water dissolving of pH value 2, is added on the polyamide column of having handled well, with the water elution of 2 times of column volumes, discards water lotion earlier, and 95% ethanol elution of 4 times of column volumes of reuse is collected eluent, reclaims ethanol, and vacuum drying, promptly gets.
Through the Radix Salviae Miltiorrhizae extract of above-mentioned prepared, yield is 1.5～2%, and Radix Salviae Miltiorrhizae total phenolic acids content is not less than 70%, and wherein content of danshinolic acid B is not less than 30%.
Ramulus Cinnamomi in the aforementioned pharmaceutical compositions can pass through reflux, extract,, vapor distillation, supercritical CO
2The prepared of the extraction volatile oil that fluid extraction, semi-bionic extraction etc. are conventional, the present invention has carried out preferably the extraction process of Ramulus Cinnamomi, as follows:
Technology one: get the Ramulus Cinnamomi medical material, be ground into coarse powder, add 5 times of amount distilled water immersion half an hour, extracted volatile oil 6 hours, promptly get.The yield of the Ramulus Cinnamomi extract that makes through this technology is 0.6～0.8%, and cinnamic aldehyde content is not less than 50%.
Technology two: get the Ramulus Cinnamomi medical material, be ground into coarse powder, add 12 times of amounts of ether supersound process secondary, each 30 minutes, filter, merging filtrate, concentrating under reduced pressure promptly gets.The yield of the Ramulus Cinnamomi extract that makes through this technology is 0.8～1.0%, and cinnamic aldehyde content is not less than 50%.
Technology three: get the Ramulus Cinnamomi pulverizing medicinal materials to certain grain size, the extraction kettle of packing into, heating SFE system, the flash trapping stage temperature is 55 ℃; Pressure is 30Mpa, and extraction temperature is 60 ℃, and the secondary separating pressure is 20Mpa, and temperature is 50 ℃; The extraction time is 3 hours, from one-level, the discharging of secondary separating still, promptly gets.The yield of the Ramulus Cinnamomi extract that makes through this technology is 0.8～1.5%, and cinnamic aldehyde content is not less than 50%.
In the aforementioned pharmaceutical compositions; Radix Salviae Miltiorrhizae wherein and Ramulus Cinnamomi all can directly be fed intake by the extract of corresponding weight portion and process; According to the yield 1.5～2.0% of Radix Salviae Miltiorrhizae extract with respect to medical material; Ramulus Cinnamomi extract calculates respectively with respect to the yield 0.8～1.5% of medical material, and the composition of processing the crude drug of the contained composition and effectiveness of this pharmaceutical composition can also be 3～100 parts of Radix Salviae Miltiorrhizae extracts, 1～30 part of Ramulus Cinnamomi extract; Be preferably: 7.5～50 parts of Radix Salviae Miltiorrhizae extracts, 1.5～15 parts of Ramulus Cinnamomi extracts; Further be preferably: 13.5～24 parts of Radix Salviae Miltiorrhizae extracts, 2.5～9 parts of Ramulus Cinnamomi extracts.In the aforementioned pharmaceutical compositions, the content of Radix Salviae Miltiorrhizae total phenolic acids is not less than 50% in the Radix Salviae Miltiorrhizae extract, and wherein the content of salvianolic acid B is not less than 30%; The content of cinnamic aldehyde is not less than 50% in the Ramulus Cinnamomi extract.In the aforementioned pharmaceutical compositions, the consumption of drug component is groped to sum up to draw through the inventor in a large number, and each amounts of components all has better curative effect in above-mentioned weight portion scope.Above-mentioned composition as if being unit with the gram, can be processed the preparation of 10～1000 consumptions, as as tablet, can be made into 10～1000, takes 1～10, every day 1～5 time at every turn; As as capsule, can be made into 10～1000, take 1～10, every day 1～5 time at every turn; As processing 10～1000ml as injection, each consumption 1～10ml, every day 1～5 time.Above-mentioned composition is by weight as proportioning, can be raw material with the kilogram like large-scale production, or is unit with the ton, and small-scale production can be unit with the gram also.Above-mentioned parts by weight are for especial patient, and the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.
This pharmaceutical composition can be used for preparing the medicine of treating cardiovascular and cerebrovascular disease.The pharmacological effect experimentation shows, this pharmaceutical composition can significantly reduce significantly to reduce the myocardial ischemia scope because of the electrocardio due to the ligation coronary artery and the abnormal change of biochemical indicator; Significantly protection Ischemic Heart function reduces average arteria coronaria pressure, coronary blood flow increasing; Significantly the Acute Myocardial Ischemia in Rats electrocardiogram changes due to the antagonism pituitrin; Significant prolongation rat experiment property carotid artery TFT; Significantly the protection cerebral ischemia reperfusion injury improves the nerve injury symptom, reduces the neuroethology scoring, reduces brain water content, dwindles ischemia side cerebral tissue infarct volume.At resisting myocardial ischemia, antithrombotic, aspects such as anti-cerebral ischemia reperfusion injury all have significant curative effect, have beyond thought effect.
Aforementioned pharmaceutical compositions; Can process clinically any or pharmaceutically acceptable dosage form with one or more mixing acceptable accessories; Preferred oral preparation or injection, with oral, snuffing is gone into or the mode of parenteral is applied to the patient who needs this treatment.
When being used for oral administration, conventional solid preparation be can be made into, tablet, capsule, granule, pill and oral solution etc. comprised.Tablet means disk shape or the special-shaped flaky solid preparation that medicine and suitable auxiliary materials and mixing compacting form; Tablet is main with oral ordinary tablet, and other has buccal tablet, Sublingual tablet, mouth paster, chewable tablet, dispersible tablet, fuse, effervescent tablet, slow releasing tablet, controlled release tablet and enteric coatel tablets etc.Capsule means medicine or is added with the adjuvant filling in Capsules or be sealed in the solid preparation in the soft capsule material; Capsule can be divided into hard capsule (being commonly referred to as capsule), soft capsule (soft gelatin capsule), slow releasing capsule, controlled release capsule and enteric coated capsule according to its dissolving and release characteristics.Granule means that medicine and suitable adjuvant process the dried particles shape preparation with certain particle size; Granule can be divided into soluble particles (being commonly referred to as granule), mix suspension grain, effervescent granule, enteric coated particles, slow-releasing granules and controlled release granule etc.Pill means medicine and suitable adjuvant uniform mixing, the spherical or near-spherical solid preparation of processing with proper method; Pill comprises drop pill, sugar pill, piller etc.Oral solution means that medicine dissolution is processed and supplies oral supernatant liquid preparation in suitable solvent.During parenteral, can be made into solution, water for injection or oil-suspending agent, the inhalant etc. of injection.Preferred dosage form is oral formulations such as sheet, capsule, soft capsule, granule, drop pill, oral liquid etc.
When being used for parenteral, can be made into injection.Injection means that confession that medicine is processed injects intravital solution, emulsion or suspension and confession and face with preceding preparation or be diluted to solution or the sterile preparation of the powder of suspension or concentrated solution, and injection can be divided into injection, injectable sterile powder and concentrated solution for injection.Injection means that the confession that medicine is processed is injected into sterile solution type injection, emulsion-type injection or the suspension type injection of using in the body, can be used for intramuscular injection, intravenous injection, intravenous drip etc.; Its specification has 1ml, 2ml, 5ml, 10ml, 20ml, 50ml, 100ml, 200ml, 250ml, 500ml etc., and big volume (generally the being not less than 100ml) injection that wherein supplies intravenous drip to use is also claimed venous transfusion.Injectable sterile powder means that confession that medicine is processed is faced with the suitable sterile solution of preceding usefulness and is mixed with settled solution or the evenly sterilized powder or the aseptic block of suspension; Available suitable solvent for injection preparation back injection, also available venous transfusion preparation posterior vein instils; Sterilized powder makes with solvent crystallization, spray drying method or freeze-drying etc.Concentrated solution for injection means that confession that medicine is processed faces the aseptic concentrated solution that supplies intravenous drip to use with preceding dilution.
The advantage of pharmaceutical composition of the present invention is:
(1) provides Radix Salviae Miltiorrhizae or its extract and Ramulus Cinnamomi or its extract to be used to prepare the compositions of treating cardiovascular and cerebrovascular diseases medicament first, and confirmed that through pharmacological evaluation both have the effect of Synergistic, are superior to both independent medications.
(3) the pharmacological effect experimentation shows, this pharmaceutical composition can significantly reduce significantly to reduce the myocardial ischemia scope because of the electrocardio due to the ligation coronary artery and the abnormal change of biochemical indicator; Significantly protection Ischemic Heart function reduces average arteria coronaria pressure, coronary blood flow increasing; Significantly the Acute Myocardial Ischemia in Rats electrocardiogram changes due to the antagonism pituitrin; Significant prolongation rat experiment property carotid artery TFT; Significantly the protection cerebral ischemia reperfusion injury improves the nerve injury symptom, reduces the neuroethology scoring, reduces brain water content, dwindles ischemia side cerebral tissue infarct volume.Above-mentioned experimental result shows that Radix Salviae Miltiorrhizae or Radix Salviae Miltiorrhizae extract and Ramulus Cinnamomi or Ramulus Cinnamomi extract drug combination have synergism aspect the treatment cardiovascular and cerebrovascular disease, and drug effect obviously strengthens, and consequently the ordinary person in present technique field institute is beyond thought.
(4) effective ingredient of pharmaceutical composition of the present invention is clear and definite, content is high, and better stability of preparation is convenient to control product quality, can guarantee clinical drug safety.
(5) quality of Radix Salviae Miltiorrhizae extract and Ramulus Cinnamomi extract is controlled, and preferable preparation technique is provided, simple and easy to do, and quality is better, is applicable to industrialized great production.
Below come further to set forth the beneficial effect of medicine according to the invention through experimental example, these experimental examples comprise the pharmacodynamic experiment of pharmaceutical composition of the present invention, the pharmaceutical composition that Radix Salviae Miltiorrhizae or its extract and Ramulus Cinnamomi or its extract are prepared from is hereinafter to be referred as DG.The used Radix Salviae Miltiorrhizae extract of experimental example all is taken from embodiment 1, and Ramulus Cinnamomi extract is all taken from embodiment 2.
Experimental example 1 DG is to the influence of myocardial ischemia due to the ligation rat coronary artery
Animal subject: Wistar rat, 300, body weight 250～280g, male and female dual-purpose.
Test sample: normal saline: commercial; DANSHEN KELI: self-control, (being equivalent to crude drug 2g); Ramulus Cinnamomi granule: self-control, (being equivalent to crude drug 1.5g); DG granule (weight proportion of Radix Salviae Miltiorrhizae and Ramulus Cinnamomi crude drug): self-control, see table 1.
Experimental technique: 300 of the qualified rats of the electrograph of coring are divided into 15 groups, 20 every group immediately.Rat is with urethane 1g/kg intraperitoneal injection of anesthesia, and back of the body position is fixing, and the record electrocardio connects artificial respirator and practices artificial respiration; Open the thoracic cavity, cut off pericardium, each administration group is pressed table 1 gastric infusion; Once a day, normal saline matched group gastric infusion normal saline 3ml falls branch before the coronary artery of ligation left side behind the 3min; Omnidistance record electrocardio 30min, 1h gets blood after the ligation, detects creatine phosphokinase (CPK) and lactic acid dehydrogenase (LDH).Take out rat heart, with 4 of the even crosscuts of ventricular muscles, 0.5% chlorination nitro tetrazole is blue to dye along ligature, and with the ischemic areas on every myocardium two sides of planimeter survey, the calculating myocardium ischemic areas accounts for the percentage ratio of ventricle area.
Experimental result and conclusion: experimental result is seen table 1.
After the ligation, the cardiac electrical QRS ripple of normal saline control rats all increases unusually suddenly, widens, and cardiac muscle is ischemia on a large scale, and biochemistry detection shows as CPK and LDH all increases unusually.Compare with the normal saline matched group, DANSHEN KELI can significantly reduce significantly to reduce myocardial ischemia scope (p＜0.05) because of the electrocardio due to the ligation coronary artery and the abnormal change (p＜0.05) of biochemical indicator; The Ramulus Cinnamomi granule can significantly reduce significantly to reduce myocardial ischemia scope (p＜0.05) because of the electrocardio due to the ligation coronary artery and the abnormal change (p＜0.05) of biochemical indicator.The DG granule can be significantly or is extremely significantly reduced extremely significantly to reduce myocardial ischemia scope (p＜0.01) because of the electrocardio due to the ligation coronary artery and the abnormal change (p＜0.05, p＜0.01) of biochemical indicator.
The DG granule can extremely significantly resist myocardial ischemia effect due to the ligation rat coronary artery, and effect is superior to single with Radix Salviae Miltiorrhizae and Ramulus Cinnamomi, points out Radix Salviae Miltiorrhizae and Ramulus Cinnamomi drug combination that collaborative function of resisting myocardial ischemia is arranged.
Table 1 DG to the influence of myocardial ischemia due to the ligation rat coronary artery (x ± s, n=20)
Annotate:
*P＜0.05,
*P＜0.01 is compared with matched group.
Experimental example 2 IDG are to the protective effect of Ischemic Heart function
Animal subject: 70 of beasle dogs, body weight 12.68kg ± 1.67kg, male and female half and half.
Test sample: normal saline: commercial; Radix Salviae Miltiorrhizae for injection extract: self-control, 24mg (being equivalent to crude drug 1.5g); Injection Ramulus Cinnamomi extract: self-control, 12mg (being equivalent to crude drug 1g); Injection DG:30mg, self-control (containing Radix Salviae Miltiorrhizae extract 18mg is equivalent to crude drug 1.5g, contains Ramulus Cinnamomi extract 6mg and be equivalent to crude drug 0.5g).
Experimental technique: the hybrid dog is divided into 7 groups at random, 10 every group: false ligation group, model group, Radix Salviae Miltiorrhizae for injection extract group, injection Ramulus Cinnamomi extract group, the high, medium and low dose groups of injection DG.Except that false ligation group and model control group give the normal saline of same amount, each administration group is according to the administration of table 2 vena femoralis injection, once-a-day.
The preparation of dog myocardial infarction and ischemia model: dog intravenous injection pentobarbital sodium (30mg/kg) anesthesia of respectively organizing of administration expiration is fixed, monitoring limbs II lead electrocardiogram; Set up the femoral vein passage, anticoagulant in the 0.5% heparin sodium body; Separate femoral artery, femoral arteriography continuous monitoring BP after the heparinization; Separate left carotid,, retouch and survey left ventricular systolic pressure, left ventricular end diastolic presssure, the maximum rate of change curve in left chamber the cardiac catheterization left ventricle; Separate trachea and intubate, and the positive pressure respiration of pedestrian worker's respirator (16～18 times/min of frequency, air-breathing: as to exhale than 1: 1.5 tidal volume 350～550m1); Open breast and expose heart, separate the left coronary artery LC, connect blood flowmeter, measure CF; Separate the below 2mm of left coronary artery anterior descending branch first branch, except that the not ligation of threading of false ligation group, all the other each groups all penetrate two No. 1 silk threads, 5min before the first phase ligation, and by per kilogram of body weight 2mg, vein splashes into lignocaine.Article one, handling diameter with one during the silk thread ligation is that No. 9 syringe needles of 1mm place between ligature and the blood vessel; After the ligation syringe needle is extracted out; Carry out the first phase ligation of angiostenosis, behind the 30min, again with the ligation of second silk thread; Carry out the second stage of ligation of bloodstream blocking, accomplish the preparation of myocardial infarction and ischemia model.
Detect index: before ligation, first phase ligation 10min, the second stage of ligation at once, 15min, 30min, 60min, 120min measure and record: left ventricular systolic pressure (LVSP), left ventricular end diastolic presssure (LVEDP), the maximum rate of change in left chamber (± index such as dp/dt).
Table 2 DG to the influence of dog mean arterial pressure and arteria coronaria blood flow (x ± s, n=10)
Annotate:
$$P＜0.01 is compared with false ligation group;
*P＜0.05,
*P＜0.01 is compared with model group.
Experimental result and conclusion: experimental result is seen table 2.
(1) behind the coronary ligation 120min, compare with false ligation group, the average arteria coronaria of model group is pressed extremely significantly and is raise, the CF border significantly reduces (p＜0.01), and the modeling success is described.
(2) compare with model group, Radix Salviae Miltiorrhizae for injection extract group and injection Ramulus Cinnamomi extract group are behind coronary ligation 120min, and average arteria coronaria is pressed and significantly reduced (p＜0.05), and CF enlarges markedly (p＜0.05); Injection DG can extremely significantly reduce average arteria coronaria pressure, coronary blood flow increasing (p＜0.01) behind coronary ligation 120min.
The effect of each dose groups of injection DG all is superior to single with Radix Salviae Miltiorrhizae extract and Ramulus Cinnamomi extract, and the Ischemic Heart function is had extremely significant protective effect.Prompting Radix Salviae Miltiorrhizae and Ramulus Cinnamomi compatibility have the effect of coordinating protection Ischemic Heart function.
Experimental example 3 DG are to the thrombotic influence of rat experiment property carotid artery
Animal subject: the Wistar rat, 210, body weight 250～280g, male.
Test sample: normal saline: commercial; Capsule of red sage root: self-control (being equivalent to crude drug 1.5g); Ramulus Cinnamomi capsule: self-control (being equivalent to crude drug 1.5g); DG capsule (weight proportion of Radix Salviae Miltiorrhizae and Ramulus Cinnamomi crude drug): self-control, see table 3.
Experimental technique: 210 rats are divided into 21 groups, 10 every group immediately.Rat is with 2.5% pentobarbital sodium (25mg/kg) intraperitoneal injection of anesthesia; Dorsal position is fixed; Separate right carotid, adopt electrical injuries carotid artery intima method, form appearance with the experimental thrombus in vivo of BT87-3 and measure different group animal carotid artery TFTs.Stimulating electrode and temperature probe are hung on the common carotid artery, press gastric infusion shown in the table 2, once-a-day; 10min begins to stimulate after the administration, and stimulus intensity is 2mA, closes the thorn energizing switch behind the stimulation 5min; Take off electrode, regulate temp controlled meter behind the 3min, observe the tremulous pulse temperature bust time to zero-bit.The record electricity irritation began to the time of aorta temperature bust, and this time is decided to be carotid artery TFT (surpassing 3000 seconds persons in 3000 seconds).
Table 3 DG to the influence of rat experiment property carotid artery TFT (x ± s, n=10)
Annotate:
*P＜0.05,
*P＜0.01 is compared with the normal saline matched group.
Experimental result and conclusion: experimental result is seen table 3.
Compare with the normal saline matched group, but Ramulus Cinnamomi significant prolongation rat experiment property carotid artery TFT (p＜0.05); But Radix Salviae Miltiorrhizae utmost point significant prolongation rat experiment property carotid artery TFT (p＜0.01).Each weight proportion group of DG is utmost point significant prolongation rat experiment property carotid artery TFT (p＜0.01) all.
But the equal experimental carotid artery TFT of prolong rats of each weight proportion of DG in 200～5000 parts of Radix Salviae Miltiorrhizaes, 100～2000 parts of scopes of Ramulus Cinnamomi; Effect all is superior to Radix Salviae Miltiorrhizae or the individually dosed effect of Ramulus Cinnamomi, and prompting Radix Salviae Miltiorrhizae and Ramulus Cinnamomi drug combination have the collaborative effect that prolongs TFT.
Experimental example 4 DG are to the protective effect of experimental rat acute myocardial ischemia
Laboratory animal: the Wistar rat, 70, body weight is at 200～220g, male and female half and half.
Test sample: normal saline, commercial; Nitroglycerine tablets, specification: 0.5mg, Beijing Yimin Pharmaceutical Co., Ltd.; Radix Salviae Miltiorrhizae Tabellae, self-control (being equivalent to crude drug 2g); The Ramulus Cinnamomi sheet, self-control (being equivalent to crude drug 1.5g); The DG sheet, self-control, (contain Radix Salviae Miltiorrhizae crude drug 1.5g, contain Ramulus Cinnamomi crude drug 1g).
Experimental technique: 70 of rats, be divided into 7 groups at random, 10 every group, be respectively the normal saline matched group, nitroglycerin group, Radix Salviae Miltiorrhizae extract group, Ramulus Cinnamomi extract group, DG low dose group, dose groups among the DG, DG high dose group.Each administration group is with normal saline and is mixed with gastric infusion behind the suspension, once a day, and continuous 7 days (nitroglycerin group before giving pituitrin sublingual vein injection 1 time).60min after the last administration in six road physiology monitors (Shanghai medical apparatus factory), connects limb lead and precordial leads with urethanes (1g/kg) intraperitoneal injection of anesthesia, in oscillograph observation and recording ecg.Behind the sublingual vein injection of pituitrin 5 μ l/kg; Immediate record V3 electrocardiogram; And respectively trace 1 time in 15s, 30s, 1min, 2min, 5min, respectively organize vein and inject and move on the ECG ST section behind the pituitrin and amplitude that the T ripple raises, and observe each group and ARR number of animals occurs.The result sees table 4.
Acute Myocardial Ischemia in Rats electrocardiogram variation due to the table 4 DG antagonism pituitrin (x ± s, n=10)
Annotate:
*P＜0.05,
*P＜0.01 is compared with the normal saline matched group.
Experimental result and conclusion: give respectively to organize behind the pituitrin and move on the ECG ST section and amplitude that the T ripple raises and number of animals that arrhythmia occurs are seen table 4.
Behind the injection of pituitrin, moving on the ST section appears in normal saline matched group most animals at once, reaches summit in the 2min, and 5min recovers basically.Raising appears in T ripple 2min at once, recover gradually, but 5min does not return to normally thereupon.Move on nitroglycerin group and the DG group ST section and raise time of occurring of T ripple consistent with matched group, but amplitude is significantly less than matched group, and recovered faster.Compare with the normal saline matched group; Radix Salviae Miltiorrhizae and Ramulus Cinnamomi all can significantly resist electrocardiogram and change (p＜0.05); Each dose groups of DG all can extremely significantly be resisted electrocardiogram and change (p＜0.01); The antagonism electrocardiogram changes, and effect is superior to single with Radix Salviae Miltiorrhizae and Ramulus Cinnamomi, points out two medicine compatibilities to have the collaborative Acute Myocardial Ischemia in Rats electrocardiogram variation effect due to the pituitrin that resists.
Experimental example 5 DG are to the protective effect of cerebral ischemia
Animal subject: Wistar rat, 140, male and female dual-purpose, body weight 200～220g.
Test sample: normal saline, commercial; The Radix Salviae Miltiorrhizae extract capsule, self-control, 36mg (being equivalent to crude drug 2g); The Ramulus Cinnamomi extract capsule, self-control, 18mg (being equivalent to crude drug 1.5g); The DG capsule, self-control, 30mg (containing Radix Salviae Miltiorrhizae extract 24mg is equivalent to crude drug 1.5g, contains Ramulus Cinnamomi extract 6mg and be equivalent to crude drug 0.5g).
Experimental technique: 140 of rats are divided into 7 groups, 20 every group at random.Rat is with 10% chloral hydrate 3ml/kg intraperitoneal injection of anesthesia, neck median incision, separation, ligation right carotid proximal part, external carotid artery and bifurcated artery thereof.Separate the right side internal carotid artery, separate wing jaw tremulous pulse downwards along internal carotid artery, this branch of root ligation.Be equipped with line, far-end placement bulldog clamp at the internal carotid artery near-end, common carotid artery crotch otch, (degree of depth is 17～20mm), fastens line and gets into internal carotid artery, goes into cranium to anterior cerebral artery, all blood flows sources of blocking-up middle cerebral artery to insert nylon wire.Remove bulldog clamp, tighten line fully, stay the long the end of a thread of 1cm outward, skin suture.Gastric infusion behind the ischemia 1h, the normal saline matched group gives normal saline, continues perfusion again behind the ischemia 1h, need not anaesthetize and cut skin once more, and prompting nylon wire head end is to the common carotid artery incision when resistance is arranged to lift institute's the end of a thread that stays gently, and blood flow is logical again.Sham operated rats is except that plug wire not, and all the other steps are the same.After the survival Mus is poured into 24h again, observe rat behavior and change, carry out behavior scoring.5 fens system standards of grading with reference to zea Longa: 0 minute, normal, impassivity damage symptom; 1 minute, can not full extension offside fore paw; 2 minutes, turn-take laterally; 3 minutes, topple over to offside; 4 minutes, can not spontaneously walk loss of consciousness.Broken end is got the Mus brain fast then.A part (10 every group) is divided another name left and right sides brain hemisphere weight in wet base, puts in 160 ℃ of baking boxs and claims dry weight behind the 24h, calculates brain water content by following formula: brain water content (%)=(weight in wet base-dry weight)/weight in wet base * 100%; A part (10 every group) is downcut the crown brain sheet of thick about 2mm on the anterior commissure plane, place 2%TIE solution at once, hatches 30min for 37 ℃.Infarct presents white, and non-infarct presents redness.Measure with planimeter (C63 image analysis system) and respectively to distinguish area, and calculate the percentage ratio (%) that infarct accounts for full brain.
Table 5 DG to the protective effect of cerebral ischemia (x ± s, n=10)
Annotate:
$$Compare with sham operated rats in p＜0.01;
*P＜0.05,
*Compare with the normal saline group in p＜0.01.
Experimental result and conclusion: experimental result is seen table 5.
(1) to the influence of behavior: all no abnormal symptom of sham operated rats rat, the neuroethology scoring is 0.The normal saline group occurs can not full extension offside fore paw or the nerve injury symptom of turn-taking laterally or toppling over to offside, and behavior scoring is 1.7 ± 0.8.Compare with ischemia-reperfusion group, Radix Salviae Miltiorrhizae extract group, Ramulus Cinnamomi extract group all can extremely significantly reduce neuroethology scoring (p＜0.05); Each dose groups of DG can extremely significantly reduce neuroethology scoring (p＜0.01).
(2) to the influence of brain water content: the brain water content utmost point of normal saline group ischemia-reperfusion side (right hemisphere) is significantly higher than sham operated rats (p＜0.01), and the modeling success is described.Compare with the normal saline group, the brain water content of Radix Salviae Miltiorrhizae extract group and Ramulus Cinnamomi extract group and each dose groups of DG all significantly reduces (p＜0.05).
(3) to the influence of infarct size: the sham operated rats cerebral tissue does not have infraction.Normal saline group ischemia side cerebral tissue has the infraction phenomenon, and infarct volume accounts for 37.33% of full brain.Compare with the normal saline group, Radix Salviae Miltiorrhizae extract group and Ramulus Cinnamomi extract group all can significantly be dwindled ischemia side cerebral tissue infarct volume (p＜0.05), and each dose groups of DG can extremely significantly be dwindled ischemia side cerebral tissue infarct volume (p＜0.01).
Above-mentioned experimental result shows that Radix Salviae Miltiorrhizae and Ramulus Cinnamomi drug combination can significantly improve the nerve injury symptom of focal brain ischemia-reperfusion injury, reduces the ischemical reperfusion injury brain water content, alleviates ischemia side brain hemisphere edema degree and dwindles cerebral infarct volume.The effect of each dose groups of DG all is superior to single with Radix Salviae Miltiorrhizae extract or Ramulus Cinnamomi extract, and prompting Radix Salviae Miltiorrhizae and Ramulus Cinnamomi drug combination have the effect of coordinating protection cerebral ischemia reperfusion injury.
[specific embodiment]
Below, foregoing of the present invention is done further to specify through the specific embodiment of embodiment form.But should this be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.The adjuvant of each dosage form can replace with acceptable accessories in following examples, perhaps reduces, increases.
The preparation and the assay of embodiment 1 Radix Salviae Miltiorrhizae extract
1, the preparation of Radix Salviae Miltiorrhizae extract
Get red rooted salvia, be ground into coarse powder, decocte with water twice adds 12 times of amounts of water for the first time, adds 10 times of amounts of water for the first time; Each 2 hours, collecting decoction filtered, and filtrate decompression is concentrated into the concentrated solution of relative density 1.10～1.15 (60 ℃); Add ethanol to containing the alcohol amount to 85%, cold preservation 24 hours filters, and filtrate recycling ethanol is to there not being the alcohol flavor; Add hydrochloric acid and transfer pH value to 2, extract 3 times, merge ethyl acetate liquid, evaporate to dryness with the ethyl acetate jolting.Residue adds the sour water dissolving of pH value 2, is added on the polyamide column of having handled well, with the water elution of 2 times of column volumes, discards water lotion earlier, and 95% ethanol elution of 4 times of column volumes of reuse is collected eluent, reclaims ethanol, and vacuum drying, promptly gets.
2, the assay of Radix Salviae Miltiorrhizae extract
Total phenolic content is measured
The preparation of reference substance solution: precision takes by weighing the protocatechualdehyde reference substance 1mg that is dried to constant weight in 105 ℃, is dissolved in water, and is settled to 100ml.
The preparation of need testing solution: precision takes by weighing sample 50mg, puts in the 50ml volumetric flask, and thin up to scale precision is measured 0.1ml and put and add ethanol 5ml in the 25ml volumetric flask; Add 0.3% sodium lauryl sulphate 2ml, 0.6% potassium ferricyanide-0.9% ferric oxide (face and use preceding mixed in equal amounts) 1ml, so 5min is placed in the dark place; Add the 0.1mol/L hydrochloric acid solution to scale, shake up, after 20min is placed in the dark place; Put in the lena colorimetric pool, the 720nm place measures.
The assay of salvianolic acid B
HPLC
Chromatographic condition and system suitability experiment: with the octadecylsilane chemically bonded silica is filler; With methanol-acetonitrile-formic acid-water (30: 10: 1: 59) be mobile phase; The detection wavelength is 286nm.Theoretical cam curve is calculated by the danshensu peak should be not less than 1500.
The preparation of reference substance solution: it is an amount of that precision takes by weighing the salvianolic acid B reference substance, adds 75% methanol and process the solution that every 1ml contains 0.14mg, promptly gets.
The preparation of need testing solution: get the about 0.2g of these article, the accurate title, decide, and puts in the tool plug conical flask, and the accurate 75% methanol 50ml that adds claims to decide weight; Reflux 1h takes out, and puts coldly, claims to decide weight again, supplies with 75% methanol to subtract weight loss; Shake up, filter, get subsequent filtrate, promptly get.
Algoscopy: accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly get.
3 batches of water-soluble extract of red sage root that make according to the method described above, wherein total phenolic acid and content of danshinolic acid B are measured the result and are seen table 7.Can find out that from the result yield of the Radix Salviae Miltiorrhizae extract that makes through this technology is 1.5～2%, Radix Salviae Miltiorrhizae total phenolic acids content is not less than 50%, and content of danshinolic acid B is not less than 30%.
The assay result and the yield of table 6 Radix Salviae Miltiorrhizae extract
The preparation and the assay of embodiment 2 Ramulus Cinnamomi extracts
1, the preparation of Ramulus Cinnamomi extract
Get the Ramulus Cinnamomi pulverizing medicinal materials to certain grain size, the extraction kettle of packing into, heating SFE system, the flash trapping stage temperature is 55 ℃; Pressure is 30Mpa, and extraction temperature is 60 ℃, and the secondary separating pressure is 20Mpa, and temperature is 50 ℃; The extraction time is 3 hours, from one-level, the discharging of secondary separating still, promptly gets.
2, the assay of Ramulus Cinnamomi extract
The cinnamic aldehyde assay
Gas chromatography:
Chromatographic condition and system suitability test: with Polyethylene Glycol (PEG)-20M is immobile phase, and coating concentration is 10%: column temperature is 190 ℃.Theoretical tray is not less than 3000.
The preparation of reference substance solution: it is an amount of to get the cinnamic aldehyde reference substance, and accurate the title decides, and adds dehydrated alcohol and processes the solution that every 1ml contains 4mg, promptly gets.
The preparation of need testing solution: get the about 50mg of these article, the accurate title, decide, and puts in the 10ml measuring bottle, adds dehydrated alcohol to scale, shakes up, and promptly gets.
Algoscopy: accurate respectively above-mentioned reference substance solution and each 3 μ l of need testing solution of drawing, inject gas chromatograph is measured, and promptly gets.
Technology five prepares three batches of Ramulus Cinnamomi extracts according to the method described above, and the content and the yield of cinnamic aldehyde are seen table 7.Can find out that from the result yield of the Ramulus Cinnamomi extract that obtains through this technology is: 0.8～1.5%, cinnamic aldehyde content is not less than 50%.
The assay result and the yield of table 7 Ramulus Cinnamomi extract
The preparation of embodiment 3 DG tablets
Prescription one:
Radix Salviae Miltiorrhizae extract 18g (being equivalent to crude drug 1kg)
Ramulus Cinnamomi extract 24g (being equivalent to crude drug 2kg)
Pregelatinized Starch 120g
Microcrystalline Cellulose 40g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 12g
Prepare 1000 altogether
Prescription two:
Radix Salviae Miltiorrhizae extract 32.4g (being equivalent to crude drug 1800g)
Ramulus Cinnamomi extract 4.8g (being equivalent to crude drug 400g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 40g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 12g
Prepare 1000 altogether
Prescription three:
Radix Salviae Miltiorrhizae extract 32.4g (being equivalent to crude drug 1800g)
Ramulus Cinnamomi extract 7.2g (being equivalent to crude drug 600g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 40g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 12g
Prepare 1000 altogether
Prescription four:
Radix Salviae Miltiorrhizae extract 43.6g (being equivalent to crude drug 5000g)
Ramulus Cinnamomi extract 4.8g (being equivalent to crude drug 400g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 40g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 12g
Prepare 1000 altogether
Preparation technology:
Radix Salviae Miltiorrhizae in the raw material and Ramulus Cinnamomi are processed extract with reference to the method for preparing among the embodiment 1,2.
(1) it is subsequent use Radix Salviae Miltiorrhizae extract and Ramulus Cinnamomi extract to be pulverized 100 mesh sieves.
(2) take by weighing raw material and adjuvant according to recipe quantity.
(3) hypromellose 2% the aqueous solution processed soluble in water is subsequent use.
(4) with Radix Salviae Miltiorrhizae extract, Ramulus Cinnamomi extract, pregelatinized Starch, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and processes suitable soft material.
(5) cross 20 mesh sieve system granules.
(6) granule is dried under 60 ℃ condition.
(7) dry good granule adds magnesium stearate and carboxymethylstach sodium, crosses 18 mesh sieve granulate, mix homogeneously.
(8) sampling, the semi-finished product chemical examination.
(9) the sheet weight sheet of confirming according to chemical examination.
(10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 4 DG capsules
Prescription one:
Radix Salviae Miltiorrhizae extract 32.4g (being equivalent to crude drug 1.8kg)
Ramulus Cinnamomi extract 24g (being equivalent to crude drug 2kg)
Pregelatinized Starch 120.0g
Microcrystalline Cellulose 50.0g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6.0g
Prepare 1000 altogether
Prescription two:
Radix Salviae Miltiorrhizae extract 43.6g (being equivalent to crude drug 2400g)
Ramulus Cinnamomi extract 7.2g (being equivalent to crude drug 600g)
Pregelatinized Starch 120.0g
Microcrystalline Cellulose 50.0g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6.0g
Prepare 1000 altogether
Prescription three:
Radix Salviae Miltiorrhizae extract 90g (being equivalent to crude drug 5000g)
Ramulus Cinnamomi extract 7.2g (being equivalent to crude drug 600g)
Pregelatinized Starch 120.0g
Microcrystalline Cellulose 50.0g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6.0g
Prepare 1000 altogether
Prescription four:
Radix Salviae Miltiorrhizae extract 90g (being equivalent to crude drug 5000g)
Ramulus Cinnamomi extract 4.8g (being equivalent to crude drug 400g)
Pregelatinized Starch 120.0g
Microcrystalline Cellulose 50.0g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6.0g
Prepare 1000 altogether
Preparation technology:
Radix Salviae Miltiorrhizae in the raw material and Ramulus Cinnamomi are processed extract with reference to the method for preparing among the embodiment 1,2.
(1) it is subsequent use Radix Salviae Miltiorrhizae extract and Ramulus Cinnamomi extract to be pulverized 100 mesh sieves.
(2) take by weighing raw material and adjuvant according to recipe quantity.
(3) hypromellose 2% the aqueous solution processed soluble in water is subsequent use.
(4) with Ramulus Cinnamomi extract, Radix Salviae Miltiorrhizae extract, pregelatinized Starch, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and processes suitable soft material.
(5) cross 20 mesh sieve system granules.
(6) granule is dried under 60 ℃ condition.
(7) dry good granule adds magnesium stearate, crosses 18 mesh sieve granulate, mix homogeneously.
(8) sampling, the semi-finished product chemical examination.
(9) loading amount of confirming according to chemical examination incapsulates.
(10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 5 DG granules
Prescription one:
Radix Salviae Miltiorrhizae extract 90g (being equivalent to crude drug 5kg)
Ramulus Cinnamomi extract 24g (being equivalent to crude drug 2kg)
Icing Sugar 450g
Dextrin 200g
Steviosin 15g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000g altogether
Prescription two:
Radix Salviae Miltiorrhizae extract 90g (being equivalent to crude drug 5kg)
Ramulus Cinnamomi extract 14.4g (being equivalent to crude drug 3kg)
Icing Sugar 450g
Dextrin 200g
Steviosin 15g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000g altogether
Prescription three:
Radix Salviae Miltiorrhizae extract 43.6g (being equivalent to crude drug 2.4kg)
Ramulus Cinnamomi extract 24g (being equivalent to crude drug 2kg)
Icing Sugar 450g
Dextrin 200g
Steviosin 15g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000g altogether
Preparation technology:
Radix Salviae Miltiorrhizae in the raw material and Ramulus Cinnamomi are processed extract with reference to the method for preparing among the embodiment 1,2.
(1) it is subsequent use sucrose to be pulverized 80 mesh sieves; It is subsequent use that Radix Salviae Miltiorrhizae extract and Ramulus Cinnamomi extract were pulverized 100 mesh sieves.
(2) take by weighing raw material and adjuvant according to recipe quantity.
(3) the method mix homogeneously that Radix Salviae Miltiorrhizae extract, Ramulus Cinnamomi extract and Icing Sugar, dextrin, steviosin is progressively increased with equivalent, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and processes suitable soft material,
(4) cross 20 mesh sieve system granules.
(5) granule is dried under 60 ℃ condition.
(6) dried granule is crossed 18 mesh sieve granulate, sprays into an amount of Fructus Citri Limoniae essence.
(7) sampling, the content of principal agent is confirmed loading amount in the semi-finished product chemical examination granule.
(8) packing, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 6 DG injection
Prescription one:
Radix Salviae Miltiorrhizae extract 18g (being equivalent to crude drug 1000g)
Ramulus Cinnamomi extract 7.2g (being equivalent to crude drug 600g)
Polyoxyethylene sorbitan monoleate 50g
Water for injection adds to 1000ml
Prepare 1000ml altogether
Prescription two:
Radix Salviae Miltiorrhizae extract 18g (being equivalent to crude drug 1kg)
Ramulus Cinnamomi extract 14.4g (being equivalent to crude drug 1.2kg)
Polyoxyethylene sorbitan monoleate 50g
Water for injection adds to 1000ml
Prepare 1000ml altogether
Concrete steps:
Radix Salviae Miltiorrhizae in the raw material and Ramulus Cinnamomi are processed extract with reference to the method for preparing among the embodiment 1,2.
(1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse;
(2) polyoxyethylene sorbitan monoleate is processed 20% aqueous solution, added the Radix Salviae Miltiorrhizae extract and the Ramulus Cinnamomi extract of recipe quantity, the heated and stirred dissolving fully;
(3) benefit adds to the full amount of water for injection;
(4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes;
(5) through sand filtration rod filtering decarbonization, measure the also pH value of regulator solution;
(6) the microporous filter membrane fine straining of warp 0.45 μ m;
(7) clarity of inspection solution, the semi-finished product chemical examination;
(8) with the solution sealing by fusing in glass ampule;
(9) 100 ℃ of flowing steam sterilizations 30 minutes;
(10) while hot sample being put into 0.01% methylene blue solution hunts leak;
(11) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 7 DG drop pill
Prescription:
Radix Salviae Miltiorrhizae extract 18g (being equivalent to crude drug 1000g)
Ramulus Cinnamomi extract 4.8g (being equivalent to crude drug 400g)
Polyethylene glycol 6000 10g
Prepare 1000 altogether
Concrete steps:
Radix Salviae Miltiorrhizae in the raw material and Ramulus Cinnamomi are processed extract with reference to the method for preparing among the embodiment 1,2.
1) polyethylene glycol 6000 heating and melting in water-bath;
2) add Radix Salviae Miltiorrhizae extract and Ramulus Cinnamomi extract, stirring and dissolving after the whole fusions of polyethylene glycol 6000;
3) crossing 60 mesh sieves filters;
4) maintenance splashes in the liquid paraffin that is chilled to below 10 ℃ for 60 ℃ and processes ball;
5) finished product is examined entirely, the packing warehouse-in.
Embodiment 8 DG preparation of soft capsule
Prescription:
Radix Salviae Miltiorrhizae extract 32.4g (being equivalent to crude drug 1.8kg)
Ramulus Cinnamomi extract 14.4g (being equivalent to crude drug 1.2kg)
Soybean oil 100g
Soybean phospholipid 8g
Cera Flava 3g
Prepare 1000 altogether
Concrete steps:
Radix Salviae Miltiorrhizae in the raw material and Ramulus Cinnamomi are processed extract with reference to the method for preparing among the embodiment 1,2.
1) soybean oil of recipe quantity and soybean phospholipid, Cera Flava heating and melting, mixing is put cold;
2) add Radix Salviae Miltiorrhizae extract and Ramulus Cinnamomi extract mixing, cross colloid mill;
3) sampling, the semi-finished product chemical examination;
4) be pressed into soft capsule;
Finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 9 DG oral liquids
Prescription:
Radix Salviae Miltiorrhizae extract 43.6g (being equivalent to crude drug 2.4kg)
Ramulus Cinnamomi extract 14.4g (being equivalent to crude drug 1.2kg)
Propylene glycol 100ml
Sodium benzoate 15g
Stevioside 10g
Purified water adds to 1000ml
Prepare 1000ml altogether
Preparation technology:
Radix Salviae Miltiorrhizae in the raw material and Ramulus Cinnamomi are processed extract with reference to the method for preparing among the embodiment 1,2.
(1) fully with heated and stirred dissolving in the purified water of Radix Salviae Miltiorrhizae extract and Ramulus Cinnamomi extract adding dosing amount 50%; It is complete to add the propylene glycol stirring and dissolving again.
(2) sodium benzoate and stevioside is complete with the water dissolution of dosing amount 20%.
(3) merge above-mentioned solution, add purified water to full dose.
(4) filtering with microporous membrane of mistake 0.8 μ m.
(5) semi-finished product chemical examination.
(6) fill, finished product is examined entirely, the packing warehouse-in.
Claims (10)
1. a pharmaceutical composition that is used for cardiovascular and cerebrovascular disease is characterized in that, calculates according to composition by weight, processes the consisting of of crude drug of the contained active ingredient of this pharmaceutical composition: 200～5000 parts of Radix Salviae Miltiorrhizaes, 100～2000 parts of Ramulus Cinnamomi.
2. pharmaceutical composition according to claim 1 is characterized in that, calculates according to composition by weight, processes the consisting of of crude drug of the contained active ingredient of this pharmaceutical composition: 500～2500 parts of Radix Salviae Miltiorrhizaes, 200～1000 parts of Ramulus Cinnamomi.
3. pharmaceutical composition according to claim 2 is characterized in that, calculates according to composition by weight, processes the consisting of of crude drug of the contained active ingredient of this pharmaceutical composition: 900～1200 parts of Radix Salviae Miltiorrhizaes, 300～600 parts of Ramulus Cinnamomi.
4. according to each described preparation of drug combination method of claim 1～3; It is characterized in that; Described Radix Salviae Miltiorrhizae and Ramulus Cinnamomi are with The suitable solvent respectively or mix through extracting processing and obtain its extract; Total extract is processed preparation with the pharmaceutic adjuvant hybrid process again, and the main effective ingredient of gained Radix Salviae Miltiorrhizae extract is a phenolic acid compound, and the main effective ingredient of Ramulus Cinnamomi extract is a volatile oil.
5. a pharmaceutical composition that is used for cardiovascular and cerebrovascular disease is characterized in that, calculates according to composition by weight, processes the consisting of of crude drug of the contained composition and effectiveness of this pharmaceutical composition: 3～100 parts of Radix Salviae Miltiorrhizae extracts, 1～30 part of Ramulus Cinnamomi extract.
6. pharmaceutical composition according to claim 5 is characterized in that, calculates according to composition by weight, processes the consisting of of crude drug of the contained composition and effectiveness of this pharmaceutical composition: 7.5～50 parts of Radix Salviae Miltiorrhizae extracts, 1.5～15 parts of Ramulus Cinnamomi extracts.
7. pharmaceutical composition according to claim 6 is characterized in that, calculates according to composition by weight, processes the consisting of of crude drug of the contained composition and effectiveness of this pharmaceutical composition: 13.5～24 parts of Radix Salviae Miltiorrhizae extracts, 2.5～9 parts of Ramulus Cinnamomi extracts.
8. according to each described pharmaceutical composition of claim 5～7, it is characterized in that the content of Radix Salviae Miltiorrhizae total phenolic acids is not less than 50% in the described Radix Salviae Miltiorrhizae extract, wherein the content of salvianolic acid B is not less than 30%; The content of cinnamic aldehyde is not less than 50% in the Ramulus Cinnamomi extract.
9. according to claim 1～3,5～7 each described pharmaceutical compositions, it is characterized in that this pharmaceutical composition and mixing acceptable accessories are processed clinically any or pharmaceutically acceptable dosage form.
10. pharmaceutical composition according to claim 9 is characterized in that, described dosage form is oral formulations or injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006100700521A CN101176751B (en) | 2006-11-09 | 2006-11-09 | Pharmaceutical composition of red sage root and cassia twig |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006100700521A CN101176751B (en) | 2006-11-09 | 2006-11-09 | Pharmaceutical composition of red sage root and cassia twig |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101176751A CN101176751A (en) | 2008-05-14 |
| CN101176751B true CN101176751B (en) | 2012-02-22 |
Family
ID=39403272
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2006100700521A Expired - Fee Related CN101176751B (en) | 2006-11-09 | 2006-11-09 | Pharmaceutical composition of red sage root and cassia twig |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101176751B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103877461A (en) * | 2014-03-07 | 2014-06-25 | 赵艳清 | Yang-warming and qi-benefiting electuary for myocardial ischemia and preparation method thereof |
| CN105168856B (en) * | 2015-09-23 | 2018-09-07 | 高原 | Treat ischaemia-reperfusion slow arrhythmia Chinese medicine preparation and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1366986A (en) * | 2001-10-26 | 2002-09-04 | 中国中医研究院中药研究所 | Cinnamon twig decoction extract for preventing and curing hypertension |
| CN1534010A (en) * | 2003-03-27 | 2004-10-06 | 成都地奥制药集团有限公司 | Water soluble extract of red sage root and its preeparation method and use |
-
2006
- 2006-11-09 CN CN2006100700521A patent/CN101176751B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1366986A (en) * | 2001-10-26 | 2002-09-04 | 中国中医研究院中药研究所 | Cinnamon twig decoction extract for preventing and curing hypertension |
| CN1534010A (en) * | 2003-03-27 | 2004-10-06 | 成都地奥制药集团有限公司 | Water soluble extract of red sage root and its preeparation method and use |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101176751A (en) | 2008-05-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1931236B (en) | Medicine composition of red sage and rhodiola root | |
| CN1931217B (en) | Medicine composition of gingko leaf and rhodiola root | |
| CN101230003B (en) | Preparation method of salvia miltiorrhiza tanshinoate A | |
| CN1923241B (en) | Medicine composition containing epimedium extract, uncaria extract, and gastrodine, and its preparation and use | |
| CN112641915A (en) | Traditional Chinese medicine ointment formula for treating palpitation and preparation method thereof | |
| CN101176751B (en) | Pharmaceutical composition of red sage root and cassia twig | |
| CN101677989A (en) | A drug composition for treatment and prevention of ischemic stroke and its preparation methods | |
| CN111000903A (en) | Traditional Chinese medicine composition for treating blood stasis type coronary heart disease angina and preparation method thereof | |
| CN101099775B (en) | Cardiac and cerebral vascular disease treating medicine | |
| CN100509009C (en) | Chinese medicinal preparation for treating heart cerebrovascular disease and ischemic apoplexia and making method thereof | |
| CN104707023A (en) | Traditional Chinese medicinal composition for treating polycystic ovary syndrome, and preparation method thereof | |
| CN1935178A (en) | Ginkgo leaf extract and barrenwort extract composition | |
| CN102204956B (en) | Chinese medicinal composition used at stroke recovery period and preparation method thereof | |
| CN101696166B (en) | Preparation method for danshen root salvianolic acid A | |
| CN105343761A (en) | Traditional Chinese medicine composition for treating myocardial infarction and preparation method thereof | |
| CN101152246B (en) | Pharmaceutical composition for cardiovascular and cerebrovascular diseases and method for preparing the same | |
| CN101190253B (en) | Medicinal composition containing mongolian snakegourd and notoginseng | |
| CN101176770B (en) | Pharmaceutical composition of folium ginkgo and cattail pollen | |
| CN101108198B (en) | Epimedium erigeron pharmaceutical composition | |
| CN106138795B (en) | Traditional Chinese medicine composition for treating premature beat and preparation method thereof | |
| CN101152247A (en) | Pharmaceutical composition for cardiovascular and cerebrovascular diseases and method for preparing the same | |
| CN100522195C (en) | Medicine composition for treating cardiovascular and cerebrovascular diseases, preparation method and use thereof | |
| CN101161268B (en) | Pharmaceutical composition of red sage root and cattail pollen | |
| CN108478706A (en) | It is a kind of to protect cardiovascular composition and preparation method thereof | |
| CN101856357A (en) | Application of rotundic acid in preparing medicines for preventing and treating cardiovascular and cerebrovascular diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20080523 Address after: Tianchen Avenue in Ji'nan high tech Development Zone of Shandong City, No. 2518 Applicant after: Shandong Xuanzhu Medical Technology Co., Ltd. Address before: Tianchen Avenue in Ji'nan high tech Development Zone in Shandong City, No. 2518, block A Applicant before: Huang Zhenhua |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: HAIAN SUSHI TECHNOLOGY TRANSFORMATION CENTER CO., Free format text: FORMER OWNER: SHANDONG XUANZHU MEDICAL TECHNOLOGY CO., LTD. Effective date: 20130930 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 250101 JINAN, SHANDONG PROVINCE TO: 226601 NANTONG, JIANGSU PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20130930 Address after: 226601 No. 8 Yingbin Road, software park, Haian County, Jiangsu Province Patentee after: Haian Su Fu Technology Transfer Center Co., Ltd. Address before: Tianchen Avenue in Ji'nan high tech Development Zone of Shandong province 250101 City No. 2518 Patentee before: Shandong Xuanzhu Medical Technology Co., Ltd. |
|
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120222 Termination date: 20191109 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |