CN116392519B - Preparation method of Bdellover and rhizoma ligustici wallichii capsules - Google Patents
Preparation method of Bdellover and rhizoma ligustici wallichii capsules Download PDFInfo
- Publication number
- CN116392519B CN116392519B CN202310064918.1A CN202310064918A CN116392519B CN 116392519 B CN116392519 B CN 116392519B CN 202310064918 A CN202310064918 A CN 202310064918A CN 116392519 B CN116392519 B CN 116392519B
- Authority
- CN
- China
- Prior art keywords
- capsule
- bdellovibro
- ethanol
- parts
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000002775 capsule Substances 0.000 title claims abstract description 153
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 241000545744 Hirudinea Species 0.000 claims abstract description 53
- 238000002156 mixing Methods 0.000 claims abstract description 15
- 238000010992 reflux Methods 0.000 claims abstract description 14
- 238000001291 vacuum drying Methods 0.000 claims abstract description 8
- 235000000604 Chrysanthemum parthenium Nutrition 0.000 claims abstract description 6
- 235000000802 Leonurus cardiaca ssp. villosus Nutrition 0.000 claims abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 85
- 239000003814 drug Substances 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 44
- 239000000284 extract Substances 0.000 claims description 28
- 239000000706 filtrate Substances 0.000 claims description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 238000001035 drying Methods 0.000 claims description 20
- 239000000843 powder Substances 0.000 claims description 20
- 229940079593 drug Drugs 0.000 claims description 18
- 238000000605 extraction Methods 0.000 claims description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- 239000012530 fluid Substances 0.000 claims description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
- 241000237903 Hirudo Species 0.000 claims description 10
- 238000010298 pulverizing process Methods 0.000 claims description 10
- 239000008187 granular material Substances 0.000 claims description 9
- 241000207925 Leonurus Species 0.000 claims description 6
- 241000112528 Ligusticum striatum Species 0.000 claims description 6
- 235000019359 magnesium stearate Nutrition 0.000 claims description 6
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 5
- 229940069328 povidone Drugs 0.000 claims description 5
- 238000001556 precipitation Methods 0.000 claims description 5
- 239000000377 silicon dioxide Substances 0.000 claims description 5
- 239000011230 binding agent Substances 0.000 claims description 4
- 230000001376 precipitating effect Effects 0.000 claims description 4
- 239000002245 particle Substances 0.000 claims description 3
- 235000012239 silicon dioxide Nutrition 0.000 claims description 3
- 238000012869 ethanol precipitation Methods 0.000 claims description 2
- 210000004369 blood Anatomy 0.000 abstract description 45
- 239000008280 blood Substances 0.000 abstract description 45
- 241000604933 Bdellovibrio Species 0.000 abstract description 35
- 230000002829 reductive effect Effects 0.000 abstract description 20
- 210000005013 brain tissue Anatomy 0.000 abstract description 9
- KSEBMYQBYZTDHS-HWKANZROSA-M (E)-Ferulic acid Natural products COC1=CC(\C=C\C([O-])=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-M 0.000 abstract description 8
- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 abstract description 8
- 229940114124 ferulic acid Drugs 0.000 abstract description 8
- KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 abstract description 8
- 235000001785 ferulic acid Nutrition 0.000 abstract description 8
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 abstract description 8
- 230000001105 regulatory effect Effects 0.000 abstract description 7
- 230000002785 anti-thrombosis Effects 0.000 abstract description 6
- 208000032843 Hemorrhage Diseases 0.000 abstract description 5
- 206010030113 Oedema Diseases 0.000 abstract description 5
- 244000046146 Pueraria lobata Species 0.000 abstract description 4
- 235000010575 Pueraria lobata Nutrition 0.000 abstract description 4
- 240000007164 Salvia officinalis Species 0.000 abstract description 4
- 235000005412 red sage Nutrition 0.000 abstract description 4
- 230000002792 vascular Effects 0.000 abstract description 4
- 230000007721 medicinal effect Effects 0.000 abstract description 2
- 240000007890 Leonurus cardiaca Species 0.000 abstract 1
- 241000212322 Levisticum officinale Species 0.000 abstract 1
- 239000001645 levisticum officinale Substances 0.000 abstract 1
- 241000700159 Rattus Species 0.000 description 51
- 208000007536 Thrombosis Diseases 0.000 description 32
- 206010065559 Cerebral arteriosclerosis Diseases 0.000 description 29
- 201000005851 intracranial arteriosclerosis Diseases 0.000 description 29
- 230000000694 effects Effects 0.000 description 20
- 230000008569 process Effects 0.000 description 19
- 230000001965 increasing effect Effects 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 210000004204 blood vessel Anatomy 0.000 description 10
- 210000004556 brain Anatomy 0.000 description 10
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 description 8
- 102100025588 Calcitonin gene-related peptide 1 Human genes 0.000 description 8
- 238000004090 dissolution Methods 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 230000002537 thrombolytic effect Effects 0.000 description 7
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 6
- 108010049003 Fibrinogen Proteins 0.000 description 6
- 102000008946 Fibrinogen Human genes 0.000 description 6
- 102000015779 HDL Lipoproteins Human genes 0.000 description 6
- 108010010234 HDL Lipoproteins Proteins 0.000 description 6
- 102000007330 LDL Lipoproteins Human genes 0.000 description 6
- 108010007622 LDL Lipoproteins Proteins 0.000 description 6
- 230000003213 activating effect Effects 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 229940012952 fibrinogen Drugs 0.000 description 6
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 6
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 5
- 229930182837 (R)-adrenaline Natural products 0.000 description 5
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- 208000031226 Hyperlipidaemia Diseases 0.000 description 5
- 206010020772 Hypertension Diseases 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 229960005139 epinephrine Drugs 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000002960 lipid emulsion Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 206010003178 Arterial thrombosis Diseases 0.000 description 4
- 102000009123 Fibrin Human genes 0.000 description 4
- 108010073385 Fibrin Proteins 0.000 description 4
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 4
- 206010019468 Hemiplegia Diseases 0.000 description 4
- 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 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- RXUWDKBZZLIASQ-UHFFFAOYSA-N Puerarin Natural products OCC1OC(Oc2c(O)cc(O)c3C(=O)C(=COc23)c4ccc(O)cc4)C(O)C(O)C1O RXUWDKBZZLIASQ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 230000009471 action Effects 0.000 description 4
- 230000023555 blood coagulation Effects 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 229950003499 fibrin Drugs 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 230000003285 pharmacodynamic effect Effects 0.000 description 4
- HKEAFJYKMMKDOR-VPRICQMDSA-N puerarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 HKEAFJYKMMKDOR-VPRICQMDSA-N 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- 150000000640 6-keto-prostaglandin F1α derivatives Chemical class 0.000 description 3
- 102000007625 Hirudins Human genes 0.000 description 3
- 108010007267 Hirudins Proteins 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 229930194268 Salvianic acid Natural products 0.000 description 3
- 108090000190 Thrombin Proteins 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 210000001772 blood platelet Anatomy 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 238000005534 hematocrit Methods 0.000 description 3
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 3
- 229940006607 hirudin Drugs 0.000 description 3
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000000518 rheometry Methods 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229960004072 thrombin Drugs 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 description 2
- 208000034657 Convalescence Diseases 0.000 description 2
- 206010013887 Dysarthria Diseases 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- 208000004044 Hypesthesia Diseases 0.000 description 2
- 208000032382 Ischaemic stroke Diseases 0.000 description 2
- 208000007443 Neurasthenia Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 201000004810 Vascular dementia Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 239000004019 antithrombin Substances 0.000 description 2
- 210000000702 aorta abdominal Anatomy 0.000 description 2
- 206010003549 asthenia Diseases 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 208000002173 dizziness Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 239000002662 enteric coated tablet Substances 0.000 description 2
- 239000008098 formaldehyde solution Substances 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 208000034783 hypoesthesia Diseases 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 230000007654 ischemic lesion Effects 0.000 description 2
- 230000037356 lipid metabolism Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 231100000862 numbness Toxicity 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 208000026473 slurred speech Diseases 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 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 1
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000022306 Cerebral injury Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 208000009084 Cold Injury Diseases 0.000 description 1
- 241001391944 Commicarpus scandens Species 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102100038124 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 229920003081 Povidone K 30 Polymers 0.000 description 1
- KNAHARQHSZJURB-UHFFFAOYSA-N Propylthiouracile Chemical compound CCCC1=CC(=O)NC(=S)N1 KNAHARQHSZJURB-UHFFFAOYSA-N 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 208000004531 Renal Artery Obstruction Diseases 0.000 description 1
- 206010038378 Renal artery stenosis Diseases 0.000 description 1
- 241000124033 Salix Species 0.000 description 1
- 208000032140 Sleepiness Diseases 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 206010047163 Vasospasm Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 206010000210 abortion Diseases 0.000 description 1
- 231100000176 abortion Toxicity 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 206010002906 aortic stenosis Diseases 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
- 230000006399 behavior Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003153 chemical reaction reagent 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
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000002595 cold damage Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 230000006397 emotional response Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- -1 extractum Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000003505 heat denaturation Methods 0.000 description 1
- 230000017525 heat dissipation Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 206010019847 hepatosplenomegaly Diseases 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000011206 morphological examination Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229940024898 povidone k30 Drugs 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229960002662 propylthiouracil Drugs 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 206010038464 renal hypertension Diseases 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 201000004409 schistosomiasis Diseases 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910021487 silica fume Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 230000037321 sleepiness Effects 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000001195 ultra high performance liquid chromatography Methods 0.000 description 1
- 230000003966 vascular damage Effects 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/62—Leeches; Worms, e.g. cestodes, tapeworms, nematodes, roundworms, earth worms, ascarids, filarias, hookworms, trichinella or taenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/236—Ligusticum (licorice-root)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/488—Pueraria (kudzu)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/533—Leonurus (motherwort)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a preparation method of a Bdelloving and rhizoma chuanxiong capsule, which comprises the steps of firstly, continuously extracting 500 parts of red sage root, 500 parts of motherwort herb and 500 parts of kudzuvine root in a hot reflux way, carrying out microwave vacuum drying, continuously extracting 500 parts of szechuan lovage rhizome in a hot reflux way, carrying out microwave vacuum drying, crushing 100 parts of leech, mixing, granulating and encapsulating. On the premise of reducing the dosage of leech, the invention not only ensures that the medicinal effect of the Bdellovibrio capsule is not reduced, but also obviously improves the content of ferulic acid, has no obvious difference with the traditional Bdellovibrio capsule in the aspects of regulating blood fat, blood viscosity and fluidity, protecting brain tissues, improving edema, congestion, vascular hemorrhage and the like, but has better antithrombotic effect on the basis of retaining the original efficacy of the traditional Bdellovibrio capsule.
Description
Technical Field
The invention belongs to the technical field of preparation of Chinese patent medicines, relates to a preparation method of a Bdellovibrio capsule, and in particular relates to a preparation method of a Bdellovibrio capsule capable of maintaining the efficacy of the Bdellovibrio capsule under the condition of reducing the dosage of leeches.
Background
Cerebral arteriosclerosis (cerebral arteriosclerosis, CAS) is a multiple-lesion syndrome in the brain, which causes damage to blood vessels in the brain due to long-term hypertension and hyperlipidemia, and causes symptoms such as arteriosclerotic dementia, ischemic stroke, neurasthenia, etc.
The Bdelloves and rhizoma Ligustici Chuanxiong capsule is prepared from Hirudo 500g, rhizoma Ligustici Chuanxiong 500g, saviae Miltiorrhizae radix 500g, radix Puerariae 500g, herba Leonuri 500g, which are obtained from Shanxi Mikang pharmaceutical industry Co., ltd., approval document: chinese medicine standard Z20163104. The Bdelloves and rhizoma Ligustici Chuanxiong capsule has effects of promoting blood circulation for removing blood stasis, dredging meridian passage, and can be used for treating cerebral arteriosclerosis and blood stasis. Leech in the formula is an animal medicine, and is used for breaking blood and removing stasis; chuan Xiong is pungent and dispersed and warm to be used as qi-flowing herb in blood; leonurus is bitter and slightly cold, and can remove blood stasis and unblock menstruation; the red sage root can remove blood stasis and promote tissue regeneration; the kudzuvine root radically treats the arthralgia and plays a role in harmonizing the medicines. It has better curative effect in clinical application.
The approved Bdelloving and Xiong capsule is prepared by decocting radix Salviae Miltiorrhizae, herba Leonuri, and radix Puerariae with water for three times (1 hr each time), mixing decoctions, filtering, concentrating the filtrate under reduced pressure to obtain fluid extract with relative density of 1.18-1.20 (58 deg.C), cooling, adding ethanol to ethanol content of 60%, standing overnight, filtering, recovering ethanol from the filtrate, concentrating to obtain soft extract with relative density of 1.38-1.40 (58 deg.C), drying under reduced pressure, and pulverizing. And additionally taking the ligusticum wallichii, preparing dry extract according to the operation, and crushing. Soaking Hirudo in water for 2 hr, decocting for three times, each time for 1 hr, mixing decoctions, filtering, concentrating the filtrate under reduced pressure to obtain fluid extract with relative density of 1.18-1.20 (58 deg.C), cooling, adding ethanol to ethanol content of 60%, standing overnight, filtering, recovering ethanol from the filtrate, drying the residue under reduced pressure, and pulverizing. Mixing the above extract powders, adding appropriate amount of starch, mixing, encapsulating, and making into 1000 granule.
Leech is a kind of blood-breaking and stasis-dispelling herb with definite clinical effect and wide application. 2015, chinese pharmacopoeia: the leech is a leech belonging to the family Hirudidae of the phylum AnemoneWhitmania pigra Whitman) Leech with willow leafWhitmania acranulata Whitman) Leech (leech)Hirudo nipponica Whitman) Is a dry body of (a).
The description of leeches was first found in Shennong Ben Cao Jing: leech taste salty and flat, mainly expelling malignant blood, blood stasis, and removing obstruction and accumulation. Zhang Jing is combined with leech in Qing Dang Tang to drain and store blood, and its "abortion" is described in Ming Yi Bie Lu, which indicates that our ancestors have early knowledge about its medical utility. In modern medicine, leeches are widely used in clinic as blood-activating and stasis-resolving drugs, and have uniqueness in blood-breaking and stasis-resolving treatment and high medicinal value. There are many countries such as Egypt and Europe where there is a tradition of the treatment of a live leech for external use.
However, whether leech is toxic or not, and the determination of a clinically safe and effective dose are quite different from each other are described in the past. The cloud leech in the book of herbal meridian hundred species is most favored by eating human blood, but is slow and easy to enter, and the blood is produced without injury if slow; when the Chinese medicinal composition is good, the hardness is easy to break, and the force is used for eliminating stagnation for a long time, so that the Chinese medicinal composition is favorable and harmless; the Shennong Ben Cao Jing is not recorded with toxicity; zhang Zhongjing has 30 leeches (about 30 g) in the Shang Han Lun; the modern Zhang Xichun is good at treating the disease, and considers that 'all blood-breaking drugs hurt qi-flowing in the blood system, but leech is salty in the blood system, so that qi-flowing in the blood system is not damaged at all', 'blood stasis-breaking but no damage to new blood'. Modern pharmacological research shows that leech contains mainly protein and hirudin, and has the functions of preventing thrombin from acting on fibrinogen, preventing blood coagulation, heparin, antithrombin and histamine-like matter, and has anticoagulant and vasodilating effects.
However, it is recorded in Ming Yi Bie Ji that leech is "toxic", while it is "toxic" in Ben Cao Jing Shu ". "Chinese medicine dictionary", higher medical teaching materials "Chinese medicine identification", chinese medicine processing and Chinese pharmacopoeia (1990 edition) are all "toxic". On the other hand, leeches have influence on a blood coagulation mechanism, and toxicity can be generated when the dosage is too large, if the leeches are reported to treat schistosomiasis hepatosplenomegaly, sallow complexion, abnormal debilitation and blood finding red blood cells, hemoglobin and blood platelets are all prone to decline after taking the leeches. These cases, in addition to the potential bleeding bias of the patient itself, may be related to the influence of leeches on the coagulation mechanism.
In recent years, the national code has regulated the daily dosage of leech for a plurality of times, the Chinese pharmacopoeia of 2005 edition is 1.5-3 g, the Chinese pharmacopoeia of 2015 edition is 1-3 g, and the effective dosage is down-regulated.
The leech dosage of the original prescription of the Bdelloving and Xiong capsule is converted into 6g according to the daily dosage of finished products, which is far higher than the highest daily dosage specified in the Chinese pharmacopoeia of 2015 edition, so the prescription dosage of the leech needs to be adjusted for safety.
The formula of the prepared Bdellovely-xiong capsule is specifically 100g of leech, 500g of ligusticum wallichii, 500g of radix salviae miltiorrhizae, 500g of radix puerariae and 500g of motherwort, and the daily dosage of the converted leech is 1.2g, thereby conforming to the prescribed dosage of the current pharmacopoeia.
However, if the prepared bdellovibro-chuanxiong capsules are prepared according to the original water decoction extraction and alcohol precipitation preparation process, the dosage change directly leads to the reduction of the efficacy of the medicine.
The national institute 16 committee of the national food and drug administration, such as the national institutes of health and medicine science and technology, and the national institutes of health, at day 3 and 21 of 2007 states that the traditional Chinese medicine pharmaceutical industry should strengthen the research and development of new processes, new technologies and new equipment conforming to the production characteristics of Chinese patent medicines and improve the modernization level of the traditional Chinese medicine manufacturing industry. The extraction technology directly influences the quality of the medicine, the utilization rate of medicinal materials resources, the production efficiency and the economic benefit. The traditional extraction method of the bdellovibro capsule mainly comprises heating, decocting and extracting, but the method is easy to leach out a large amount of impurities, brings great difficulty to the subsequent process, and has easy decomposition or loss of active ingredients and low transfer rate.
Disclosure of Invention
The invention aims to provide a novel preparation method of a bdellovibro capsule, which ensures that the medicinal effect of the bdellovibro capsule is not reduced on the premise of reducing the dosage of leech in the bdellovibro capsule.
The invention relates to a bdellovibro-chuanxiong capsule which is prepared from the following raw materials in parts by mass: 100 parts of leech, 500 parts of ligusticum wallichii, 500 parts of radix salviae miltiorrhizae, 500 parts of radix puerariae and 500 parts of motherwort, and is prepared according to the following method:
extracting Saviae Miltiorrhizae radix, herba Leonuri and radix Puerariae with water under continuous thermal reflux for 3 hr, collecting filtrate, concentrating to obtain fluid extract, precipitating with ethanol, collecting filtrate, recovering ethanol, concentrating to obtain soft extract, vacuum drying with microwave, and pulverizing into fine powder;
extracting rhizoma Ligustici Chuanxiong with water under continuous thermal reflux for 3 hr, collecting filtrate, concentrating into fluid extract, precipitating with ethanol, collecting filtrate, recovering ethanol, concentrating into soft extract, vacuum drying with microwave, and pulverizing into fine powder;
pulverizing Hirudo, mixing with the above fine powder to obtain medicinal fine powder, adding silicon dioxide micropowder, granulating with povidone ethanol solution as binder, drying, adding magnesium stearate, mixing, and making into capsule.
Wherein, the filtrate obtained by continuous thermal reflux extraction is decompressed and concentrated to the clear paste with the relative density of 1.18-1.20 at 58 ℃.
Wherein, the filtrate obtained after alcohol precipitation is recovered with ethanol and concentrated to thick paste with the relative density of 1.38-1.40 at 58 ℃.
Further, when the clear paste is subjected to alcohol precipitation treatment, specifically, ethanol is added into the clear paste to enable the volume content of the alcohol to reach 60%, and the clear paste is left to stand overnight for alcohol precipitation.
Still further, the water addition amount of the continuous thermal reflux extraction is preferably 10 times the mass of the medicine.
More specifically, the invention is to add silica micropowder with the mass of 3% of the drug fine powder into the mixed drug fine powder.
More specifically, the invention is to add magnesium stearate with the mass of 0.3% of the drug particles into the drug particles.
Still further, the present invention preferably uses povidone ethanol solution with a concentration of 5% as the binder.
Leech is used as a classical blood-breaking and stasis-removing animal drug, and is processed and used as a drug in Shang Han Zhang Zhongjing (Shang Han Lun treatise on Cold injury), and the traditional drug-taking mode is mainly treated at high temperature. Zhang Zhong Jing is three prescriptions for treating blood syndrome by combining leech in Shang Han Lun and jin Kui Yao LWD: resisting decoction, resisting pill, and radix et rhizoma Rhei insect pill. The decoction time of the pill and the decoction is shorter than that of other formulas, so that the leech is supposed to be difficult to decoct for a long time, and the effective components are supposed to be destroyed at high temperature after the leech is decocted for a long time.
Modern famous doctor Zhang Xichun, who claims leech to be used in the book of Yi Zhong Shen xi, indicates that it is most suitable for use because of the essence generation of pure water and is contraindicated for moxibustion with fire. Stir-baked, it is ineffective in treating water-related disorders due to its impairment of essence and qi. Zhang Xichun it is used to treat mass of women: ' Hirudo alone is thoroughly roasted with sesame oil and is in powder form. Five minutes per day, twice daily, no effect, and the later change to the life, such as former administration. The condition that the leech is destroyed by high temperature is also proved by the condition that the leech is not completely taken and the mass is eliminated … ….
The main active component of the leech is hirudin, which is a small molecular protein (polypeptide) composed of 65-66 amino acids. The protein has heat denaturation property, and the water decoction and extraction can cause the change of physicochemical property and biochemical property and the loss of biological activity. The antithrombin activity of the leech water decoction is detected by adopting a content measuring method under leech items in China pharmacopoeia of 2015 edition, and the thrombin activity of the leech water decoction cannot be detected. Therefore, the rationality of high temperature decoction of leeches is questioned, which may lead to inactivation and loss of hirudin as the main active ingredient in leeches. Furthermore, 60% ethanol precipitation also aggravates the loss of protein components contained in the leech water decoction.
In view of the above, in order to fully embody the potency or effectiveness of the leech, the invention changes the water decoction and extraction process of the leech into direct raw powder for use.
The continuous extraction method of thermal reflux is a widely applied energy-saving traditional Chinese medicine extraction method in recent years, wherein extracting solution is continuously pumped into a concentrator from the bottom of an extraction tank for concentration in the extraction and concentration process, and secondary steam generated by concentration is continuously sent into the extraction tank as new solvent supplement after condensation, so that the concentration of soluble substances in medicinal materials and solvents is always kept high gradient, and solutes in the medicinal materials are dissolved out at high speed, thereby achieving the effect of rapid extraction.
The traditional Chinese medicine extract is mostly dried under normal pressure or vacuum reduced pressure, and the methods have the defects of long drying time, high drying temperature, different products of dried products, high energy consumption, low production efficiency and the like. The microwave drying technology has the advantages of uniform heating, high drying speed, high drying efficiency, good product quality, sterilization function and the like, and is widely applied to drying of traditional Chinese medicine extracts, extractum, powder and the like. The invention changes the extract drying mode in the original process from a vacuum low-temperature drying method to a microwave vacuum low-temperature drying method.
Specifically, the invention carries out microwave vacuum drying on the prepared thick paste at 40-60 ℃ by using microwaves of 2KW and 2450+/-50 MHz under the vacuum degree of 0.08 Mpa.
Significantly, the invention discovers through process research that the adopted hot reflux continuous extraction process and the microwave vacuum low-temperature drying process are not only simple and optimized replacement of the traditional process by the new process, but also can directly influence the content of chemical components in the extract and the final drug effect.
The detection of the content of the main components of the bdellovibro capsules prepared by the method provided by the invention is compared with the bdellovibro capsules prepared by the traditional prescribed method, and the result shows that the bdellovibro capsules prepared by the method have little reduction of the content of puerarin and sodium salvianic acid A, but have no statistical difference compared with the traditional method. However, in the Bdelloving and chuing capsule prepared by the method, the ferulic acid content is obviously increased, and the method has statistical significance.
Ferulic acid is one of the main components of rhizoma Ligustici Chuanxiong, and has effects in increasing coronary blood flow, protecting ischemic myocardium and improving myocardial oxygen supply and demand imbalance. In addition, the ferulic acid also has the effects of resisting platelet aggregation, inhibiting platelet 5-hydroxytryptamine release, inhibiting platelet thromboxane A2 (TXA 2) generation, enhancing prostaglandin activity, relieving pain, relieving vasospasm and the like. Therefore, the combination of the function of the Bdellovibrio capsule mainly treats the functions of activating blood circulation to dissipate blood stasis and clearing and activating the channels and collaterals, and can clearly determine the ferulic acid as the main active pharmaceutical ingredient of the Bdellovibrio capsule.
The invention only adjusts and reduces the prescription dosage of leech in the Bdellovibrio capsule, the prescription dosage of other medicines is not changed, but the content of ferulic acid is obviously increased from 0.106mg/g of the traditional Bdellovibrio capsule to 0.912mg/g of the Bdellovibrio capsule under the condition that the effective components of other medicines including puerarin, sodium salvianic acid and the like are not obviously changed through the adjustment of an extraction process and a drying mode.
The invention adjusts the prescription quantity and the extraction process of the leech in order to meet the requirements of safety, not only can the adjusted dosage meet the requirements of the current pharmacopoeia, but also the drug effect is ensured to be maintained after the prescription quantity is reduced.
The invention adjusts the fluidity and hygroscopicity of the medicine, and the like, and correspondingly adjusts the forming auxiliary materials such as adhesive, wetting agent and the like, wets and adheres the medicine fine powder to form granules so as to increase the fluidity of the medicine, reduce the adsorption of the fine powder and store air, and facilitate the filling of capsules.
According to the invention, indexes such as fluidity, hygroscopicity, loading difference and the like are used for respectively inspecting the lubricant, the adhesive and the wetting agent, and finally, the addition amount of magnesium stearate in the forming process is 0.3%, the addition amount of micro silica gel is 3%, and the dosage of povidone ethanol solution is 15g/100g for wet granulation.
The results of pharmacodynamics research on the Bdellovely-rhizoma capsules prepared by the method disclosed by the invention are compared with the Bdellovely-rhizoma capsules prepared by the traditional process, and the results show that the two Bdellovely-rhizoma capsules have obvious treatment effects on CAS model rats, thrombosis model rats and mice, and have no obvious difference in the aspects of regulating blood fat, blood viscosity and fluidity, protecting brain tissue structures of CAS model rats, improving edema, congestion, vascular hemorrhage and the like. However, in the aspect of antithrombotic, the effect of the Bdellovibrio capsule prepared by the method in thrombolysis and thrombosis inhibition is superior to that of the Bdellovibrio capsule prepared by the traditional process.
Therefore, the Bdellovibrio capsule prepared by the method has better antithrombotic effect on the basis of retaining the original efficacy of the Bdellovibrio capsule in the traditional process.
Drawings
FIG. 1 is a CAS model rat brain histopathological examination (mirror 200 times).
FIG. 2 is a pathological morphology observation (mirror 200 times) of thrombus in rats.
Description of the embodiments
The following examples illustrate the invention in further detail. The following examples are presented only to more clearly illustrate the technical aspects of the present invention so that those skilled in the art can better understand and utilize the present invention without limiting the scope of the present invention.
The production process, the experimental method or the detection method related to the embodiment of the invention are all conventional methods in the prior art unless otherwise specified, and the names and/or the abbreviations thereof are all conventional names in the art, so that the related application fields are very clear and definite, and a person skilled in the art can understand the conventional process steps according to the names and apply corresponding equipment to implement according to conventional conditions or conditions suggested by manufacturers.
The various instruments, equipment, materials or reagents used in the examples of the present invention are not particularly limited in source, and may be conventional products commercially available through regular commercial routes or may be prepared according to conventional methods well known to those skilled in the art.
Examples
Example 1
Taking 500g of red sage root, 500g of motherwort and 500g of kudzuvine root, adding 10 times of water, continuously extracting for 3 hours by hot reflux, filtering, concentrating the filtrate under reduced pressure to obtain clear paste with the relative density of 1.18-1.20 (58 ℃), cooling, adding ethanol to ensure that the ethanol content reaches 60%, standing overnight, filtering, recovering ethanol from the filtrate, concentrating to obtain thick paste with the relative density of 1.38-1.40 (58 ℃), carrying out microwave vacuum drying at 60 ℃ by microwaves of 2KW and 2450+/-50 MHz under the vacuum degree of 0.08Mpa, and crushing.
500g of Ligusticum wallichii is taken, 10 times of water is added, the mixture is continuously extracted for 3 hours under the condition of thermal reflux, the mixture is filtered, the filtrate is concentrated into clear paste with the relative density of 1.18-1.20 (58 ℃), the clear paste is cooled, ethanol is added to enable the ethanol content to reach 60%, the mixture is stood overnight, the filtrate is filtered, the ethanol is recovered from the filtrate, the filtrate is concentrated into thick paste with the relative density of 1.38-1.40 (58 ℃), and the thick paste is dried under the vacuum degree of 0.08Mpa by microwaves of 2KW and 2450+/-50 MHz under the vacuum condition of microwave drying under the vacuum condition of 60 ℃ and crushing.
100g of leech is cleaned and crushed into fine powder.
Mixing the above extract powder with Hirudo powder, adding silicon dioxide, granulating with 5% povidone k30 ethanol solution, drying, adding magnesium stearate, mixing, and making into capsule with a filling amount of 0.34g.
The preparation of the medicament in this example is hereinafter referred to simply as bdellovibro capsule (new).
The indications are as follows: it has the actions of activating blood and resolving stasis, and clearing and activating the channels and collaterals. Can be used for treating dizziness, headache, slurred speech, and numbness and pain of limbs caused by cerebral arteriosclerosis and apoplexy due to blood stasis and obstruction of collaterals in convalescence.
The usage amount is as follows: orally taken, 4 granules at a time, 3 times a day.
Comparative example 1.
Decocting 500g of red sage root, 500g of motherwort and 500g of kudzuvine root in water for three times, each time for 1 hour, combining decoctions, filtering, concentrating the filtrate under reduced pressure to obtain fluid extract with the relative density of 1.18-1.20 (58 ℃), cooling, adding ethanol to ensure that the ethanol content reaches 60%, standing overnight, filtering, recovering ethanol from the filtrate, concentrating to obtain thick paste with the relative density of 1.38-1.40 (58 ℃), drying under reduced pressure to prepare dry extract, and crushing.
Decocting 500g of Ligusticum wallichii in water for three times each for 1 hour, mixing decoctions, filtering, concentrating the filtrate under reduced pressure to obtain fluid extract with the relative density of 1.18-1.20 (58 ℃), cooling, adding ethanol to reach the alcohol content of 60%, standing overnight, filtering, recovering ethanol from the filtrate, concentrating to obtain thick paste with the relative density of 1.38-1.40 (58 ℃), drying under reduced pressure to obtain dry extract, and pulverizing.
Soaking Hirudo 500g in water for 2 hr, decocting for three times each for 1 hr, mixing decoctions, filtering, concentrating the filtrate under reduced pressure to obtain fluid extract with relative density of 1.18-1.20 (58 deg.C), cooling, adding ethanol to ethanol content of 60%, standing overnight, filtering, recovering ethanol from the filtrate, drying the residue under reduced pressure to obtain dry extract, and pulverizing.
Mixing the above 3 dry extracts, adding appropriate amount of starch, mixing, and making into capsule, 1000 capsules of Hirudo, each capsule having a filling amount of 0.30g.
The preparation of the medicine of this comparative example is hereinafter referred to simply as bdellovibro capsule (original).
The indications are as follows: it has the actions of activating blood and resolving stasis, and clearing and activating the channels and collaterals. Can be used for treating dizziness, headache, slurred speech, and numbness and pain of limbs caused by cerebral arteriosclerosis and apoplexy due to blood stasis and obstruction of collaterals in convalescence.
The usage amount is as follows: orally taken, 4 granules at a time, 3 times a day.
Application example 1
The effective components of the bdellovibro capsule (new) and the bdellovibro capsule (original) prepared by two processes are respectively adopted for analysis aiming at the example 1 and the comparative example 1, and the puerarin, sodium salvianic acid and ferulic acid content in the samples are detected by adopting an ultra-high performance liquid chromatography.
Chromatographic conditions: chromatographic column: zorbax SB-C18 (2.1X100 mm,1.8 μm); detection wavelength: 254 280, 328nm; mobile phase: gradient elution is carried out for 0-20min by acetonitrile-0.2% glacial acetic acid solution (5:95-20:80); column temperature: 30 ℃.
The specific detection results are shown in Table 1.
Through the analysis of the comparison experiment results of the two processes, the content of ferulic acid in the process of the embodiment 1 is higher than that in the process of the comparative embodiment 1 in the core index of the examination, and the content of puerarin and sodium salvianic acid is not obviously different.
The pharmacodynamic effects of the Bdellovely-Xiong capsules on cerebral arteriosclerosis and blood stasis are prepared by examining different processes, and the main pharmacodynamic effect difference and the rationality of process change of the Bdellovely-Xiong capsules (new) and the Bdellovely-Xiong capsules (original) are evaluated.
The test medicine was prepared as an example to prepare a Bdellovibrio capsule (new) produced by Shanxi pharmaceutical Co., ltd.
The Bdelloving and rhizoma ligustici wallichii capsule (new) does not contain auxiliary materials, and the clinical dosage is 4 granules for one time, 3 times a day, and each granule is 0.34g for oral administration. The clinical daily dosage of the medicine is converted into the equivalent dosage of the rat to be 0.441g/kg, and the equivalent dosage of the medicine is converted into the equivalent dosage of the mouse to be 0.882g/kg.
The capsule content is prepared into a concentration of 0.044g/ml by distilled water for the gastric lavage administration of rats, and the administration volume of the rats is 1ml/100g; the concentration of 0.088g/ml is prepared by the same method, and the administration volume of the mice is 0.25ml/10g.
The control Hirudo-rhizoma Ligustici Chuanxiong capsule (original) has definite therapeutic effect on cerebral arteriosclerosis and blood stasis, and can be used as reference medicine for functional comparison of Hirudo-rhizoma Ligustici Chuanxiong capsule (new).
The clinical dosage of the Bdelloving and Xiong capsule (original) is 4 granules for one time, 3 times a day, and each granule is 0.30g for oral administration. The clinical dosage of the medicine is converted into the equivalent dosage of the rat to be 0.385g/kg, the equivalent dosage of the mouse to be 0.770g/kg, distilled water is respectively prepared into 0.039g/ml and 0.077g/ml which are respectively used for the gastric lavage administration of the rat and the mouse, and the administration volume is the same as that of the bdellovide capsule (new).
Application example 2: the experimental study of the Bdellovely xiong capsule for treating the hypertension complicated with hyperlipidemia Cerebral Arteriosclerosis (CAS) model rat.
Replication of CAS model rats: taking healthy SD rats, feeding male and female halves with basic feed adaptively for 7d, and then, taking rats in the normal value range (128+/-0.9 mmHg, 134+/-1.1 mmHg) after feeding with basic feed without water forbidden for 12h, and performing bilateral renal aortic stenosis operation to narrow the rats by about 3/4, thereby forming a renal hypertension model of the rats; blood pressure was measured again 10 days after the operation, and a rat meeting the standard (blood pressure: 160 mmHg) was lavaged and given 10mL ∙ kg of a warm 35℃high-fat emulsion -1 (proportion: lard 15%, cholesterol 7%, sodium cholate 2%, propylthiouracil 1%), 2 times daily, total 8w, establish the CAS rat model of hypertension combined with hyperlipidemia.
When the 4w of the high-fat emulsion is given, the serum of the model rat is extracted, the TC value and the TG value are detected, and the rat which does not meet the standard (TC is less than 2.09mmol/l, TG is less than 2.31mmol/l, TG is less than 1.05mmol/l, TG is less than 1.36 mmol/l) are removed. Rats meeting the standard are randomly divided into a model group, a bdellovibro capsule (original) group and a bdellovibro capsule (new) group, and the administration of the high-fat emulsion is continued until the 8 th w is finished.
The SD rats were also isolated from bilateral renal arteries, not stenosed, and fed basal feed as a blank group.
At the beginning of molding at the 4w, the corresponding medicines of each group are respectively administered, and the leech and the chuanxiong rhizome are respectively administeredCapsule (original) group 0.385g ∙ kg -1 Bdelloving and Xiong capsule (New) group 0.441g ∙ kg -1 The administration volume was 1ml/100g, and the blank group and model group were administered with an equal volume of physiological saline 1 time a day for 4w.
The body mass of the rats was measured every week, and the administration dose was adjusted. Skin hair, emotional response, behavioral state, active conditions, etc. of the animals were observed during the administration period.
After the last administration, the patients are fasted and not forbidden for 12 hours, sodium pentobarbital is anesthetized, abdominal aorta blood is taken, and a full-automatic hemorheometer is adopted to detect blood rheology indexes such as blood plasma viscosity, hematocrit, erythrocyte aggregation index, rigidity index and the like of rats; measuring HDL and LDL levels by using a full-automatic blood biochemical analyzer; detecting the content of CGRP and ET-1 in serum by adopting an ELISA method; weighing brain and calculating brain index; the right half brain tissue is taken and cut along the coronal plane, 10% formaldehyde solution is used for fixation, paraffin embedding, slicing and HE staining are carried out, and the pathological morphological observation of cerebral arteriosclerosis degree, cerebral ischemia, injury and the like is carried out by observing the HE staining 200 times with a light microscope.
During the period of high-fat emulsion gastric lavage and molding, the hair of the rat is dull and matt, the emotion is easy to be irritated after renal artery stenosis operation, the reaction is more sensitive, the behavior is more active, and the rat has slow reaction and sleepiness in the later period of high-fat emulsion gastric lavage. The quality of the rats in the blank group continuously and slowly increases, but is lower than that of the rats in other groups; the quality of the rats in the model group and each administration group rapidly increases from 6w, and obvious difference appears compared with the blank group; there was no significant difference in body mass between the dosing groups.
The results of the blood rheology index detection are shown in Table 2.
Compared with a blank group, the indexes of the CAS model group such as the plasma viscosity, the erythrocyte aggregation index, the rigidity index, the hematocrit and the like of the rat are obviously increased, so that the modeling is successful.
Compared with the model group, after the last administration, the plasma viscosity, the erythrocyte aggregation index, the rigidity index, the hematocrit and the like of rats in the Bdelloving and chuanxiong capsule (original) group and the Bdelloving and chuanxiong capsule (new) group are obviously reduced, and the comprehensive analysis on the aspect of blood flow change index regulation can show that the effective dose of the Bdelloving and chuanxiong capsule (new) is lower than or equal to that of the Bdelloving and chuanxiong capsule (original), and no obvious statistical difference exists between the Bdelloving and chuing capsule (original).
The results of the lipid metabolism test are shown in Table 3, and the LDL level of the rats in the model group is increased, HDL level is decreased, and the success of modeling is indicated. Compared with the model group, the Bdellovely-rhizoma Ligustici Chuanxiong capsule (new) group and the Bdellovely-rhizoma Ligustici capsule (original) group have the advantages of low LDL, high HDL, and no obvious difference in the actions of raising HDL and lowering LDL levels.
After the last administration, the content of CGRP and ET-1 in the serum of the rat was detected, and the results are shown in Table 4.
The CGRP content of the model group is obviously reduced, and the ET-1 content is obviously increased compared with that of the blank group. After administration, the CGRP of rats in the Bdellovibrio capsule (new) group and the Bdellovibrio capsule (original) group are obviously increased, the ET-1 level also has a descending trend, but has no obvious difference compared with the model group; the Bdellovely (new) group of capsules has no obvious statistical difference from the Bdellovely (original) group of capsules in the effect of increasing CGRP and reducing ET-1 level.
After the end of the administration, the brain index of the rat is measured, and the result shows that the brain index of the model group is obviously increased compared with that of the blank group, thereby prompting the success of model creation. The brain indexes of the bdellovibro capsule (original) group and the bdellovibro capsule (new) group are obviously reduced compared with the model group, and the two groups have no statistical difference (table 5).
The pathological morphological examination of the brain tissue of the CAS rat model is carried out under the light microscope (200 times), and the result of the figure 1 shows that the brain tissue structure of the rats in the blank group (A) is clear, the blood vessels have no phenomena of expansion, congestion, edema and the like, and the symptoms of ischemic lesions of the brain tissue and cerebral vascular arteriosclerosis are avoided; the brain tissue of the rat in the model group (B) can be widely denatured, necrotized and shed by endothelial cells of the intima of arterial blood vessels, fibrous hat-like accumulation, bud-like protrusion and hyperplasia are visible on the tube wall, which indicates that ischemic lesions of the brain tissue and cerebral arteriosclerosis symptoms are formed, obvious lesions such as vasodilation, congestion, hemorrhage, nerve cell edema and the like are generated, and the success of modeling is indicated; after administration, the bdellovibro capsule (original) group (C) and the bdellovibro capsule (new) group (D) both show that lesions are relieved to different degrees, and blood vessel distension and congestion are still visible, but the wall fiber cap-like accumulation and hyperplasia of the bdellovibro capsule (new) group are more obvious than that of the bdellovibro capsule (original) group, and the blood vessel congestion degree of the bdellovibro capsule (original) group is relieved than that of the bdellovibro capsule (new) group.
Cerebral Arteriosclerosis (CAS) is a syndrome of multiple lesions of the brain, and causes vascular damage to the brain due to long-term hypertension and hyperlipidemia, and has symptoms such as arteriosclerotic dementia, ischemic stroke, neurasthenia, etc. The Bdelloves and rhizoma Ligustici Chuanxiong capsule comprises Hirudo, rhizoma Ligustici Chuanxiong, saviae Miltiorrhizae radix, radix Puerariae, and herba Leonuri, and has effects of promoting blood circulation for removing blood stasis, dredging meridian passage, and can be used for treating cerebral arteriosclerosis and blood stasis. The invention changes the technology and prescription amount to improve the resource bioavailability.
The experiment selects rats as experimental objects to establish a cerebral arteriosclerosis model of hypertension and hyperlipidemia, takes cerebral index, hemorheology, low density lipoprotein, high density lipoprotein and the like as detection indexes, observes the influence of the Bdellovely-chuanxiong capsules on the blood rheology and the blood lipid metabolism level of the cerebral arteriosclerosis rats, and shows that the Bdellovely-chuanxiong capsules (new) and the Bdellovely-chuanxiong capsules (original) can both reduce the cerebral index of the rats, reduce the blood viscosity, dilate blood vessels and increase the blood fluidity, can also reduce LDL and raise HDL level, obviously improve lipid metabolism disorder, reduce or reduce the risk factors of cerebral arteriosclerosis and have positive treatment effect on cerebral arteriosclerosis.
CGRP is a strong vasodilator in vivo and has a regulating effect on blood vessels, and can promote the increase of intracellular cyclic adenosine monophosphate level, promote prostaglandin release and exert the biological effect of dilating blood vessels. The Bdelloving and chuing capsules (new) and the Bdelloving and chuing capsules (original) can effectively raise the content of CGRP, have no obvious difference in regulating the action of CGRP, and ensure the effectiveness of treating cerebral arteriosclerosis after changing the process.
Application example 3: experimental study on in vitro antithrombotic effect of Bdelloving and Xiong capsules.
Heart blood of healthy New Zealand big ear rabbit is taken for 10ml, coagulated at room temperature, and after 60min, coagulated blood blocks are taken out and cut into 0.15cm 3 Size, whole blood clot is prepared.
2ml of fibrinogen solution (containing no plasmin and no plasminogen) was taken at a concentration of 20mg/ml, and 2ml (10 u ∙ ml) was added -1 ) Thrombin, which forms a clot and is removed and cut into 0.1cm pieces 3 Size, fibrin clot was prepared.
The control solution was Tris-HCl buffer at ph=7.4.
The prepared whole blood clot and pure fibrin clot are respectively put into a bdellovibro capsule (new) solution group, a bdellovibro capsule (original) solution group and a control solution (all 600 mu l solution), and are placed into a constant-temperature water bath box at 37 ℃ for heat preservation and dissolution, the mass of the residual thrombus segment is respectively measured in 24 hours and 48 hours, and the thrombolysis rate is calculated.
The dissolution rate of the whole blood clot in different time periods is observed, and finally at 48 hours, the dissolution rates of the bdellovibro capsule (original) group and the bdellovibro capsule (new) group on the whole blood clot are good, and the dissolution rates of the bdellovibro capsule (new) group on the whole blood clot have a descending trend, but have no statistical difference compared with a control group, and have no statistical difference compared with the control group, and are shown in table 6.
Experimental results show that at 48 hours, the dissolution rates of the bdellovibro capsule (original) group and the bdellovibro capsule (new) group on the fibrin clot are good, and the dissolution rates have a descending trend, but have no statistical difference compared with the comparison group; compared with the Bdellovibrio capsule (original) group, the dissolution rate of the Bdellovibrio capsule (new) group is higher than that of the Bdellovibrio capsule (original) group within 48 hours, and the dissolution rate is shown in table 7.
Application example 4: experimental study on influence of Bdelloving and Xiong capsules on collagen and epinephrine induced thrombus in mice.
Healthy KM mice are taken, 18-20g of the mice are divided into a model group, an aspirin enteric-coated tablet group, a bdellovibro capsule (original) group and a bdellovibro capsule (new) group at random, and the mice are continuously administrated for 7d and 1 time a day. Wherein 16.918mg ∙ kg of aspirin enteric-coated tablet group -1 Bdelloving and rhizoma Ligustici Chuanxiong capsule (original) group 0.770g ∙ kg -1 Bdelloving and xiong capsule (New) group 0.882g ∙ kg -1 。
After the last administration for 1 hour, the mice were modeled by intravenous injection of a mixed inducer of collagen and epinephrine (225 μg/9 μg/4), and the death number of the mice within 5min and the unrecoverable number of hemiplegia within 15min were observed.
Experimental results show that the Bdellovely, the Bdellovely and the Aspirin can obviously reduce the mortality and the hemiplegia rate of mice with thrombus models, and the specific results are shown in Table 8.
Compared with a model group, the Bdellovely-rhizoma ligustici wallichii capsule (original) group and the Bdellovir capsule (new) group both reduce the death rate, simultaneously reduce the hemiplegia rate, and the two dosage forms of the Bdellovir capsule can reduce or relieve the occurrence rate of the serious thrombus in the mice induced by collagen and epinephrine to a certain extent, and have no obvious difference compared with the two dosage forms.
Application example 5: bdelloving and chuing capsule pair FeCl 3 Experimental study of the influence of the arterial thrombosis model in the induced mice.
Healthy SD rats are selected, the male and female rats are respectively half, 180-220g, and after 1 week of adaptive breeding, the rats are randomly divided into blank groups, model groups and aspirin groups (8.459 mg ∙ kg) -1 ) Bdelloving and chuing capsule (original) group and Bdelloving and chuing capsule (new) groupEach group of animals was dosed by gavage according to the respective drug dose, 1 time daily, for 7 consecutive days, during which time the rats were free to drink and eat.
After each group of rats was last dosed for 1h, 10% chloral hydrate (0.035 ml ∙ kg) -1 ) Anesthesia, separating left common carotid artery 2cm, placing 1.5cm×2.0cm tinfoil below, protecting perivascular tissue, sucking 2.16mol/l FeCl 3 A small filter paper (1 cm. Times.lcm) of the solution was applied to the exposed arterial surface (filter paper sheet was adhered to the vessel wall), and a blank of physiological saline was applied, and after 15min of the application, the filter paper sheet was removed (timing was started from the application of the filter paper sheet), to prepare a rat arterial thrombus model.
After 15min, blood is collected from abdominal aorta of each group of rats, part of the blood is placed in an anticoagulation tube, centrifugation is carried out at 4 ℃ for 10min at 1500r/min, a blood coagulation analyzer is used for measuring blood coagulation related indexes, the rest is placed in an EP tube, after standing for 2h at room temperature, centrifugation is carried out at 4 ℃ for 15min at 3000r/min, supernatant is taken, and a microplate detector is used for measuring TXB 2 6-keto-PGF1α, t-PA content.
Finally, cutting off blood vessels at the thrombus occurrence part, fixing by 10% formaldehyde solution, embedding paraffin, slicing, HE staining, and observing thrombus pathological change by using a light microscope by 200 times.
In FeCl 3 In the induced in vivo arterial thrombosis experiment, the PT and APTT time of a model group is shortened, the FIB content is increased, and compared with a blank group, the model group has statistical difference, so that the model is successfully modeled.
After administration, the Bdellovibrio capsule (new) group and the Bdellovibrio capsule (original) group can prolong PT and APTT, and have statistical difference compared with the model group; the content of the FIB of the Bdellovely-rhizoma ligustici wallichii capsule (new) group and the Bdellovely-rhizoma ligustici wallichii capsule (original) group is obviously lower than that of the model group; the specific results are shown in Table 9.
Further, the serum test results in Table 10 show that model set TXB 2 The content is obviously increased, the content of 6-keto-PGF1α and t-PA is obviously reduced, and the statistical difference is provided compared with a blank group; after the last administration, the Bdellovely Xiong Capsule (New) group and Bdellovely XiongCapsule (original) group and aspirin group TXB 2 The content is obviously reduced, and the content of 6-keto-PGF1α and t-PA is obviously increased; and the content of t-PA increased by the Bdellovibrio capsule (new) group is obviously better than that of the Bdellovibrio capsule (original) group.
The experimental results show that the Bdellovely-rhizoma ligustici wallichii capsule (new) group and the Bdellovir-rhizoma ligustici wallichii capsule (original) group can both prolong the Prothrombin Time (PT) and the Activated Partial Thromboplastin Time (APTT) of a model rat, reduce the content of Fibrinogen (FIB), and especially the effect of increasing the content of t-PA of the Bdellovely-rhizoma ligustici wallichii capsule (new) group is obviously superior to that of the Bdellovely-rhizoma ligustici wallichii capsule (original) group, thus showing that the Bdellovely-rhizoma ligustici wallichii capsule (new) group has outstanding advantages in reducing platelet aggregation, adhesion and thrombosis.
The observation results of the rat thrombus pathology under the microscope at 200 times are shown in fig. 2.
In the figure, no obvious abnormality was found in the blood vessels of the blank group (a); model group (B) intravascular thrombosis and see severe thrombosis (+ ++). Aspirin group (C) has slight or slight thrombosis (+or++), and Bdellovibrio capsule (new) group (D) and Bdellovibrio capsule (original) group (E) also have various degrees of effects of inhibiting or relieving thrombosis. [ note: "+" indicates the extent of the lesion, "+" indicates light, "++" indicates light, "+++" means the degree of the mixture is moderate, the mixture is stable, in (a) the degree of the heat dissipation.
Platelet aggregation, which is an important cause of thrombus formation, is the pathological basis of ischemic cardiovascular and cerebrovascular diseases. The invention induces a mouse in-vivo thrombus model and FeCl by in-vitro thrombolysis, collagen and epinephrine 3 The influence of the Bdellovibrio capsule on platelet aggregation and thrombosis is researched by inducing an in-vivo arterial thrombosis model, and the platelet aggregation resistance and thrombosis resistance of the Bdellovibrio capsule are discussed.
In an in vitro thrombolysis experiment, the thrombolysis effect of the bdellovibro capsule (new) of the whole blood clot and the fibrin clot at 48 hours is higher than that of the bdellovibro capsule (original), and the bdellovibro capsule (new) thrombolysis maintenance time is longer than that of the bdellovibro capsule (original), so the bdellovibro capsule (new) can be considered as a long-acting thrombolytic drug.
In the experiment of collagen and epinephrine induced thrombus in mice, the Bdellovely and Xiongxiong capsules (new) and Bdellovely and Xiongxiong capsules (original) can obviously reduce the mortality and hemiplegia rate of thrombus model mice, but the emphasis is different. And in FeCl 3 In the experiment of inducing in vivo arterial thrombosis, the advantages of the Bdellovibrio capsule (new) in reducing platelet aggregation, adhesion and thrombosis are more prominent than that of the Bdellovibrio capsule (original).
In conclusion, the Bdellovely chuanxiong capsule (new) can still ensure the same efficacy as the Bdellovely chuanxiong capsule (original) after changing the process and the prescription amount, and has better antithrombotic effect.
The pharmacodynamics research results show that the Bdellovibrio capsules (new) and the Bdellovibrio capsules (original) have remarkable treatment effects on the CAS model rats and the thrombus model rats and mice. The effects of the Bdellovibrio capsule (new) and the Bdellovibrio capsule (original) are not obviously different in the aspects of regulating blood fat, blood viscosity and fluidity, protecting the brain tissue structure of a CAS model rat, improving edema, congestion, vascular hemorrhage and the like; in the aspect of resisting thrombus, the effect of the bdellovibro capsule (new) in thrombolysis and inhibiting thrombus formation is better than that of the bdellovibro capsule (original). Therefore, the Bdellovely-rhizoma ligustici wallichii capsule (new) has better antithrombotic effect on the basis of retaining the original efficacy of the Bdellovely-rhizoma ligustici wallichii capsule (original).
The above embodiments of the invention are not intended to be exhaustive or to limit the invention to the precise forms disclosed. Various changes, modifications, substitutions and alterations may be made by those skilled in the art without departing from the principles and spirit of the invention, and it is intended that the invention encompass all such changes, modifications and alterations as fall within the scope of the invention.
Claims (9)
1. A preparation method of a bdellovibro-chuanxiong capsule is characterized in that the bdellovibro-chuanxiong capsule is prepared from the following medicines in parts by mass: 100 parts of leech, 500 parts of ligusticum wallichii, 500 parts of radix salviae miltiorrhizae, 500 parts of radix puerariae and 500 parts of motherwort, and is prepared according to the following method:
extracting Saviae Miltiorrhizae radix, herba Leonuri and radix Puerariae with water under continuous thermal reflux for 3 hr, collecting filtrate, concentrating to obtain fluid extract, precipitating with ethanol, collecting filtrate, recovering ethanol, concentrating to obtain soft extract, vacuum drying with microwave, and pulverizing into fine powder;
extracting rhizoma Ligustici Chuanxiong with water under continuous thermal reflux for 3 hr, collecting filtrate, concentrating into fluid extract, precipitating with ethanol, collecting filtrate, recovering ethanol, concentrating into soft extract, vacuum drying with microwave, and pulverizing into fine powder;
pulverizing Hirudo, mixing with the above fine powder to obtain medicinal fine powder, adding silicon dioxide micropowder, making into medicinal granule with povidone ethanol solution as binder, drying, adding magnesium stearate, mixing, and making into capsule.
2. The method for preparing the bdellovibro capsule according to claim 1, wherein the filtrate obtained by continuous hot reflux extraction is decompressed and concentrated to fluid extract with the relative density of 1.18-1.20 at 58 ℃.
3. The method for preparing the bdellovibro capsule according to claim 1, wherein the filtrate obtained after alcohol precipitation is recovered with ethanol and concentrated to a thick paste with a relative density of 1.38-1.40 at 58 ℃.
4. The method for preparing the bdellovibro capsule according to claim 1, wherein ethanol is added into the fluid extract to enable the volume content of the ethanol to reach 60%, and the fluid extract is left to stand overnight for ethanol precipitation.
5. The method for preparing a bdellovibro capsule according to claim 1, characterized in that the water addition amount of the continuous thermal reflux extraction is 10 times of the medicine mass.
6. The method for preparing the bdellovibro capsule according to claim 1, wherein the thick paste is dried in a microwave vacuum at 40-60 ℃ under a vacuum degree of 0.08Mpa by using microwaves of 2KW and 2450 + -50 MHz.
7. The method for preparing the bdellovibro capsule according to claim 1, wherein 3% of silica micropowder by mass of the drug fine powder is added.
8. The method for preparing the bdellovibro capsule according to claim 1, wherein the magnesium stearate accounting for 0.3% of the mass of the medicinal particles is added.
9. The method for preparing the bdellovibro capsule according to claim 1, wherein povidone ethanol solution with concentration of 5% is used as a binder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310064918.1A CN116392519B (en) | 2023-02-06 | 2023-02-06 | Preparation method of Bdellover and rhizoma ligustici wallichii capsules |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310064918.1A CN116392519B (en) | 2023-02-06 | 2023-02-06 | Preparation method of Bdellover and rhizoma ligustici wallichii capsules |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116392519A CN116392519A (en) | 2023-07-07 |
| CN116392519B true CN116392519B (en) | 2024-01-30 |
Family
ID=87008093
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310064918.1A Active CN116392519B (en) | 2023-02-06 | 2023-02-06 | Preparation method of Bdellover and rhizoma ligustici wallichii capsules |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116392519B (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1513522A (en) * | 2003-08-20 | 2004-07-21 | 山东华鲁制药有限公司 | Chiese patent drug for treating apoplexia and its preparation method |
| CN102688374A (en) * | 2012-06-07 | 2012-09-26 | 山西省中医药研究院 | Medicament for treating hyperplasia of mammary glands |
| CN105418726A (en) * | 2015-12-25 | 2016-03-23 | 山西省中医药研究院 | Total saponin extract of marsdenia tenacissima and extraction method thereof |
| CN108159382A (en) * | 2018-02-12 | 2018-06-15 | 山西省中医药研究院 | A kind of medicine of insomnia with anxiety-depression |
| CN111407796A (en) * | 2020-02-11 | 2020-07-14 | 沈阳药科大学 | Medical application of leech and ligusticum wallichii capsule in treating non-alcoholic fatty liver disease |
-
2023
- 2023-02-06 CN CN202310064918.1A patent/CN116392519B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1513522A (en) * | 2003-08-20 | 2004-07-21 | 山东华鲁制药有限公司 | Chiese patent drug for treating apoplexia and its preparation method |
| CN102688374A (en) * | 2012-06-07 | 2012-09-26 | 山西省中医药研究院 | Medicament for treating hyperplasia of mammary glands |
| CN105418726A (en) * | 2015-12-25 | 2016-03-23 | 山西省中医药研究院 | Total saponin extract of marsdenia tenacissima and extraction method thereof |
| CN108159382A (en) * | 2018-02-12 | 2018-06-15 | 山西省中医药研究院 | A kind of medicine of insomnia with anxiety-depression |
| CN111407796A (en) * | 2020-02-11 | 2020-07-14 | 沈阳药科大学 | Medical application of leech and ligusticum wallichii capsule in treating non-alcoholic fatty liver disease |
Non-Patent Citations (4)
| Title |
|---|
| 芎芷镇痛胶囊质量标准的研究;倪艳，等;中国实验方剂学杂志(第05期);第5-7页 * |
| 芪蛭通络胶囊的质量标准研究;杨睿，等;中药新药与临床药理;第21卷(第05期);第542-547页 * |
| 蛭芎胶囊工艺变更前后对脑动脉硬化模型大鼠的 影响;李佳，等;中国药理学与毒理学杂志;第33卷(第10期);第811页 * |
| 蛭芎胶囊联合氯吡格雷治疗缺血性脑卒中的临床研究;李涛，等;现代药物与临床;第35卷(第07期);第1390-1393页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116392519A (en) | 2023-07-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101219161B (en) | Dracocephalum moldavica extract and dracocephalum moldavica dropping pills, and method of preparing the same | |
| WO2002032438A1 (en) | Pharmaceutical composition treating gynecological blood stasis diseases, cardio and cerebral vascular diseases, respiratory diseases and the like | |
| CN111773211B (en) | Application of haemagglutinin in preparation of anti-rheumatoid arthritis drugs | |
| CN116392519B (en) | Preparation method of Bdellover and rhizoma ligustici wallichii capsules | |
| JPH05186360A (en) | Therapeutic agent for allergic disease and production of acanthopanax senticosus extract | |
| CN103655791B (en) | A kind of lotus leaf-based preparation for treating phlegm and blood stasis simultaneously and application thereof | |
| CN106668348A (en) | Pharmaceutical composition for treating diabetic retinopathy | |
| CN109224038B (en) | Traditional Chinese medicine composition containing channel-inducing medicine evodia rutaecarpa for treating blood stasis collateral blocking type hepatic fibrosis and preparation method and application thereof | |
| CN106938010A (en) | A kind of dendrobium nobile flower tea with effect for reducing blood fat and preparation method thereof | |
| CN103830374B (en) | The application in hyperuricemia clearly of three leaf glycolipids | |
| CN101829271B (en) | Chinese medicinal compound with function of treating diabetes and preparation method and application thereof | |
| CN105380985B (en) | Pharmaceutical composition for treating cerebral arterial thrombosis | |
| CN100453093C (en) | Medicine for transient cerebral ischemia attack and its preparation | |
| WO2021051261A1 (en) | Novel use of chinese medicine composition | |
| CN104587047B (en) | A kind of Chinese medicine composition for being used to treat cardiovascular and cerebrovascular disease | |
| CN107137682A (en) | A kind of Chinese medicine composition for treating apoplexy and application | |
| CN104161849B (en) | A kind of Chinese medicinal tablet treating diabetic retinopathy and application thereof | |
| CN115109135B (en) | Eupolyphaga Seu Steleophaga protein extract with liver cancer resisting and liver fibrosis inhibiting effects and its application | |
| CN102940656B (en) | Medicine composition for treating benign prostatic hyperplasia | |
| CN102743456B (en) | The application of a kind of Chinese medicine composition in the medicine of preparation control delayed encephalopathy after acute carbon monoxide poisoning | |
| CN110151941B (en) | A Chinese medicinal composition with effects of promoting blood circulation, removing blood stasis, inducing resuscitation, relieving pain, activating qi-flowing and dredging collaterals, and its preparation method | |
| CN101411765B (en) | Use of Chinese medicinal composition in preparing medicament for treating metabolism syndrome | |
| CN105641016A (en) | Pharmaceutical composition for treating coronary heart disease | |
| CN116270923A (en) | Chinese medicinal preparation for treating diabetic retinopathy | |
| CN105596429B (en) | Preparation and application of lotus plumule total flavonoids for preventing and treating type II diabetes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |