CN1989992A - Compound recipe pharmaceutical composition of traditional Chinese medicine and Western medicine for treating liver diseases - Google Patents
Compound recipe pharmaceutical composition of traditional Chinese medicine and Western medicine for treating liver diseases Download PDFInfo
- Publication number
- CN1989992A CN1989992A CN 200510131120 CN200510131120A CN1989992A CN 1989992 A CN1989992 A CN 1989992A CN 200510131120 CN200510131120 CN 200510131120 CN 200510131120 A CN200510131120 A CN 200510131120A CN 1989992 A CN1989992 A CN 1989992A
- Authority
- CN
- China
- Prior art keywords
- gynostemmae pentaphylli
- herb gynostemmae
- group
- diisopropylamine
- total glycosides
- 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.)
- Granted
Links
- 239000003814 drug Substances 0.000 title claims description 34
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 27
- 208000019423 liver disease Diseases 0.000 title abstract description 10
- 150000001875 compounds Chemical class 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims abstract description 70
- 238000002360 preparation method Methods 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 239000000890 drug combination Substances 0.000 claims abstract description 9
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical class OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 claims abstract description 4
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 81
- 150000002338 glycosides Chemical class 0.000 claims description 81
- 229930182470 glycoside Natural products 0.000 claims description 70
- 229940043279 diisopropylamine Drugs 0.000 claims description 27
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 22
- 229940079593 drug Drugs 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 14
- 239000000284 extract Substances 0.000 claims description 12
- 229940072107 ascorbate Drugs 0.000 claims description 11
- 235000010323 ascorbic acid Nutrition 0.000 claims description 11
- 239000011668 ascorbic acid Substances 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 6
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000004615 ingredient Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 238000012545 processing Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 abstract description 37
- 238000002347 injection Methods 0.000 abstract description 37
- 238000005516 engineering process Methods 0.000 abstract description 14
- FBFMBWCLBGQEBU-RXMALORBSA-N (2s,3r,4s,5s,6r)-2-[(2r,3r,4s,5s,6r)-2-[[(3s,5r,6s,8r,9r,10r,12r,13r,14r,17s)-3,12-dihydroxy-4,4,8,10,14-pentamethyl-17-[(2s)-6-methyl-2-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhept-5-en-2-yl]-2,3,5,6,7,9,11,12,13,15,16,17-dodecah Chemical class O([C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(C[C@@H]([C@H]4C(C)(C)[C@@H](O)CC[C@]4(C)[C@H]3C[C@H]2O)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O FBFMBWCLBGQEBU-RXMALORBSA-N 0.000 abstract description 8
- 235000002956 Gynostemma pentaphyllum Nutrition 0.000 abstract description 7
- 229930187479 gypenoside Natural products 0.000 abstract description 4
- 241001065361 Gynostemma Species 0.000 abstract description 3
- 238000009472 formulation Methods 0.000 abstract description 3
- 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 abstract 1
- ILKBHIBYKSHTKQ-UHFFFAOYSA-N Diisopropylamine dichloroacetate Chemical compound OC(=O)C(Cl)Cl.CC(C)NC(C)C ILKBHIBYKSHTKQ-UHFFFAOYSA-N 0.000 description 71
- 229940084113 diisopropylamine dichloroacetate Drugs 0.000 description 54
- 239000000243 solution Substances 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- 210000004185 liver Anatomy 0.000 description 27
- 230000000694 effects Effects 0.000 description 22
- 235000002639 sodium chloride Nutrition 0.000 description 19
- 238000012360 testing method Methods 0.000 description 17
- 239000008215 water for injection Substances 0.000 description 17
- 239000007788 liquid Substances 0.000 description 16
- 210000002966 serum Anatomy 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 239000008187 granular material Substances 0.000 description 15
- 208000004930 Fatty Liver Diseases 0.000 description 14
- 206010019708 Hepatic steatosis Diseases 0.000 description 14
- 208000010706 fatty liver disease Diseases 0.000 description 14
- 231100000240 steatosis hepatitis Toxicity 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 241000700159 Rattus Species 0.000 description 13
- 208000006454 hepatitis Diseases 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 230000003203 everyday effect Effects 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 10
- 239000000523 sample Substances 0.000 description 10
- 230000001154 acute effect Effects 0.000 description 9
- 239000004227 calcium gluconate Substances 0.000 description 9
- 235000013927 calcium gluconate Nutrition 0.000 description 9
- 229960004494 calcium gluconate Drugs 0.000 description 9
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 9
- 239000002131 composite material Substances 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 229920001214 Polysorbate 60 Polymers 0.000 description 8
- 238000001802 infusion Methods 0.000 description 8
- 230000003908 liver function Effects 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 238000012856 packing Methods 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- MSXHSNHNTORCAW-GGLLEASOSA-M sodium;(2s,3s,4s,5r,6s)-3,4,5,6-tetrahydroxyoxane-2-carboxylate Chemical compound [Na+].O[C@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O MSXHSNHNTORCAW-GGLLEASOSA-M 0.000 description 8
- 210000000952 spleen Anatomy 0.000 description 8
- 210000003462 vein Anatomy 0.000 description 8
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000007689 inspection Methods 0.000 description 7
- 239000011265 semifinished product Substances 0.000 description 7
- 230000002195 synergetic effect Effects 0.000 description 7
- 238000005303 weighing Methods 0.000 description 7
- 206010008909 Chronic Hepatitis Diseases 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
- 102000007330 LDL Lipoproteins Human genes 0.000 description 6
- 108010007622 LDL Lipoproteins Proteins 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 235000001727 glucose Nutrition 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 239000012567 medical material Substances 0.000 description 6
- 230000001681 protective effect Effects 0.000 description 6
- 239000013558 reference substance Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 5
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 5
- 206010019668 Hepatic fibrosis Diseases 0.000 description 5
- 101710098398 Probable alanine aminotransferase, mitochondrial Proteins 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 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 5
- 229920002674 hyaluronan Polymers 0.000 description 5
- 229960003160 hyaluronic acid Drugs 0.000 description 5
- -1 lipid peroxide Chemical class 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 241000272525 Anas platyrhynchos Species 0.000 description 4
- 206010016654 Fibrosis Diseases 0.000 description 4
- 240000006509 Gynostemma pentaphyllum Species 0.000 description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 4
- 206010068676 Pneumoretroperitoneum Diseases 0.000 description 4
- 208000005727 Retropneumoperitoneum Diseases 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 4
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 208000019425 cirrhosis of liver Diseases 0.000 description 4
- 238000005262 decarbonization Methods 0.000 description 4
- 230000004761 fibrosis Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 235000019634 flavors Nutrition 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 231100000753 hepatic injury Toxicity 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000008108 microcrystalline cellulose Substances 0.000 description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 description 4
- 239000000312 peanut oil Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000000630 rising effect Effects 0.000 description 4
- 238000009287 sand filtration Methods 0.000 description 4
- 238000001694 spray drying Methods 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 241000725618 Duck hepatitis B virus Species 0.000 description 3
- 102000015779 HDL Lipoproteins Human genes 0.000 description 3
- 108010010234 HDL Lipoproteins Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 206010067125 Liver injury Diseases 0.000 description 3
- 229960004150 aciclovir Drugs 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000011010 flushing procedure Methods 0.000 description 3
- 239000013505 freshwater Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 208000002672 hepatitis B Diseases 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 238000004321 preservation Methods 0.000 description 3
- 238000004064 recycling Methods 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000007779 soft material Substances 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 2
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 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 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 238000011284 combination treatment Methods 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 206010019692 hepatic necrosis Diseases 0.000 description 2
- 230000007866 hepatic necrosis Effects 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 230000002443 hepatoprotective effect Effects 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229960003943 hypromellose Drugs 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 206010025482 malaise Diseases 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- BLKQDSMHWQPNJU-UHFFFAOYSA-N n-(cyanomethyl)-n-(furan-2-ylmethyl)-3,4-dimethoxybenzenesulfonamide Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)N(CC#N)CC1=CC=CO1 BLKQDSMHWQPNJU-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 229930182490 saponin Natural products 0.000 description 2
- 150000007949 saponins Chemical class 0.000 description 2
- 235000017709 saponins Nutrition 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 230000000405 serological effect Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 239000008227 sterile water for injection Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000272522 Anas Species 0.000 description 1
- 206010002700 Anterior pituitary hyperfunction Diseases 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 208000037171 Hypercorticoidism Diseases 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- YEZWWUMWIFKEQM-UHFFFAOYSA-N O.OC.ClC(Cl)Cl.CCOC(C)=O Chemical compound O.OC.ClC(Cl)Cl.CCOC(C)=O YEZWWUMWIFKEQM-UHFFFAOYSA-N 0.000 description 1
- 201000002451 Overnutrition Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 201000007981 Reye syndrome Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 206010041660 Splenomegaly Diseases 0.000 description 1
- 231100000643 Substance intoxication Toxicity 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282894 Sus scrofa domesticus Species 0.000 description 1
- YTGJWQPHMWSCST-UHFFFAOYSA-N Tiopronin Chemical group CC(S)C(=O)NCC(O)=O YTGJWQPHMWSCST-UHFFFAOYSA-N 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229940086234 acetaminophen 300 mg Drugs 0.000 description 1
- 231100000354 acute hepatitis Toxicity 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 201000005255 adrenal gland hyperfunction Diseases 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003851 biochemical process Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- 229940099352 cholate Drugs 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound 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 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 230000009514 concussion Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000009088 enzymatic function Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- ZRBFCAALKKNCJG-UHFFFAOYSA-N gypenoside-XVII Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OC(CO)C(O)C(O)C1O ZRBFCAALKKNCJG-UHFFFAOYSA-N 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 210000003701 histiocyte Anatomy 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 239000006101 laboratory sample Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000011147 magnesium chloride Nutrition 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 210000000713 mesentery Anatomy 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000020823 overnutrition Nutrition 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 238000005325 percolation Methods 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229940023488 pill Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- ZEMGGZBWXRYJHK-UHFFFAOYSA-N thiouracil Chemical compound O=C1C=CNC(=S)N1 ZEMGGZBWXRYJHK-UHFFFAOYSA-N 0.000 description 1
- 229950000329 thiouracil Drugs 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of medical technology, discloses a novel drug combinations and its preparation methods, the drug combinations mainly made by gynostemma pentaphylla and pantanevril or its acceptable pharmaceutical salt, and its weight ratio is: gynostemma pentaphylla 400 ~ 10000, pantanevril or its acceptable pharmaceutical salt 4 ~ 100. Or by gypenosides and pantanevril or its acceptable pharmaceutical salt, and its weight ratio is: gypenosides 12 ~ 300, pantanevril or its acceptablepharmaceutical salt 4 ~ 100. Among them, the pantanevril or its acceptable pharmaceutical salt optimizes dichloroacetic acid salt and ascorbic acid salt. The drug combination can be made to any clinical or pharmaceutical acceptable formulations and the injection and oral formulations is prepared. The drug combinations mainly apply to liver disease.
Description
1, technical field
The invention belongs to medical technical field, relate to a kind of pharmaceutical composition of mainly making by Herb Gynostemmae Pentaphylli or its extract and diisopropylamine or its pharmaceutically acceptable salt, and its production and use.
2, background technology
Hepatopathy is commonly encountered diseases and frequently-occurring disease, especially occupy an leading position in China by the caused acute and chronic hepatopathy of viral hepatitis, the sickness rate height, wide coverage, only hepatitis B China just has 1.2 hundred million people to be viral infection, and annual about 300,000 people are because of hepatopathy death, and wherein half is a preinvasive cancer, this shows that hepatopathy is very harmful to people ' s health.
According to the interrelated data statistics, at present, the sickness rate of China adult fatty liver is about 10%, and fatty liver is in clinical commonly encountered diseases, the frequently-occurring disease of having become.Fatty liver is not an independent disease, but a kind of pathological phenomenon of the liver that multiple factor (or disease) all can form, factors (or disease) such as overnutrition, malnutrition, parenteral hyperalimentation, drug intoxication, heavy drinking, diabetes, inflammation, gestation, application 17-hydroxy-11-dehydrocorticosterone, Reye syndrome, hypercortisolism, hyperthyroidism, anterior pituitary hyperfunction, chronic ulcerative colitis, crohn, Peptic Ulcers and chronic hepatitis all can cause fatty liver.
Hepatic disease such as hepatitis, fatty liver has become serious harm China people ' s health and has needed preferential public health and the social problem that solves.
Herb Gynostemmae Pentaphylli is the dry herb of cucurbitaceous plant Herb Gynostemmae Pentaphylli Gynostemma pentaphylium (Thunb.) Mak., has another name called Herba Gynostemmatis etc.Bitter in the mouth, little sweet, cold in nature; Has heat-clearing and toxic substances removing, supplementing QI and nourishing YIN, the effect of slow down aging.Modern study shows that the main effective ingredient of Herb Gynostemmae Pentaphylli is the total saponins class.The Herb Gynostemmae Pentaphylli total glycosides main pharmacological is: anticancer, enhance immunity, defying age, blood fat reducing; in addition; Herb Gynostemmae Pentaphylli total glycosides also has the effect of good anti-hepatitis; its mechanism of action is: 1. suppress the increase of glutamate pyruvate transaminase (GPT) rising regulating liver-QI lipid peroxide; reduce the rat acute hepatic injury; hepatocellular degeneration, inflammatory infiltration, necrosis etc. all there are obvious protective effect, promote hepatocellular regeneration.2. the immunocompromised animal there is significant enhance immunity effect.Herb Gynostemmae Pentaphylli total glycosides by increasing the chronic viral hepatitis B patient cellular immune function and reduce the effect that the lipid peroxide level realizes its treatment hepatitis B.
The diisopropylamine pharmaceutical salts of listing at present has dichloroacetic acid salt and Ascorbate, and both all have therapeutical effect preferably to acute, chronic hepatitis.Diisopropylamine dichloroacetate has recorded into the 14th 64 pages of national drug standards chemical drugs provincial standard rising national standards (Chinese Pharmacopoeia Commission's volume), and wherein regulation is pressed dry product calculating, contains C
8H
17O
2NCl
12Must not be less than 98.5%.Diisopropylamine dichloroacetate has good hepatoprotective effect, can promote the liver steatolysis, reduces intrahepatic fat and assembles, and suppresses the synthetic of liver tg, and it is synthetic to suppress fatty acid, thus treatment and prevention fatty liver.It also can improve the liver function, promote impaired hepatocellular reparation, dwindle the scope of hepatic necrosis and the formation of inhibition fibrosis tissue, promote hepatocyte growth and differentiation, can increase liver weight and protein content, increase hepatocellular oxygen uptake, improve the function of histiocyte breathing and oxygen breathing rate, promote membrane phospholipid sequentially methylate, the flowability of enhance hepatocyte film, be used for the auxiliary treatment of acute and chronic hepatitis.The diisopropylamine Ascorbate has another name called diisopropylamine ascorbate, has recorded into the 6th 217 pages of national drug standards chemical drugs provincial standard rising national standards (Chinese Pharmacopoeia Commission's volume), and wherein regulation is pressed dry product calculating, contains C12H23NO6 and must not be less than 98.5%.That diisopropylamine ascorbate is mainly used in is chronic, the auxiliary treatment of persisting type hepatitis and acute hepatitis.The structural formula of diisopropylamine dichloroacetate and diisopropylamine ascorbate is as follows:
Diisopropylamine dichloroacetate
Diisopropylamine Ascorbate (diisopropylamine ascorbate)
At present, utilize the interaction of Herb Gynostemmae Pentaphylli and diisopropylamine dichloroacetate or diisopropylamine Ascorbate (diisopropylamine ascorbate), composition of prescription, the medicine that is used to prepare hepatic disease such as treatment acute, chronic hepatitis, fatty liver yet there are no report.
3, summary of the invention
In order to meet clinical needs, to the invention provides a kind of new pharmaceutical composition that is used for the treatment of hepatic disease, and its preparation method is provided.
Pharmaceutical composition of the present invention is mainly made by Herb Gynostemmae Pentaphylli and diisopropylamine or its salt of pharmaceutically accepting, and its parts by weight are: 4～100 parts of 400～10000 parts of Herb Gynostemmae Pentaphylli, diisopropylamine or its pharmaceutically acceptable salts; Be preferably: 10～40 parts of 1000～4000 parts of Herb Gynostemmae Pentaphylli, diisopropylamine or its pharmaceutically acceptable salts; The best is: 20 parts of 2000 parts of Herb Gynostemmae Pentaphylli, diisopropylamine or its pharmaceutically acceptable salts.
Herb Gynostemmae Pentaphylli can obtain its extract through extracting processing with The suitable solvent, and extract is made various preparations with diisopropylamine or its pharmaceutically acceptable salt, pharmaceutic adjuvant hybrid process again.Contained main effective ingredient is a Herb Gynostemmae Pentaphylli total glycosides in the Herb Gynostemmae Pentaphylli extract, and its content is not less than 30%.
Herb Gynostemmae Pentaphylli can obtain Herb Gynostemmae Pentaphylli total glycosides through extracting processing with The suitable solvent, extract solvent preferred alcohol or water, the extracting method of Herb Gynostemmae Pentaphylli can be infusion process, percolation, decocting method, reflux extraction or continuous extraction, can also prepare according to literature method.
The invention provides the preferred for preparation technology (is main effective ingredient with Herb Gynostemmae Pentaphylli total glycosides) of a kind of Herb Gynostemmae Pentaphylli, specific as follows:
Get the Herb Gynostemmae Pentaphylli medical material, add 75% alcohol reflux secondary, each 2 hours, filter, flow liquid reclaims ethanol to there not being the alcohol flavor, adds water and makes into the solution that every 1ml is equivalent to 2g crude drug amount, stirs evenly, put coldly, standing over night filters, the macroporous resin column of filtrate by having handled well, earlier with the water of 2 times of column volumes towards post, discard water liquid, 60% ethanol of 3 times of column volumes of reuse carries out eluting, collects eluent, reclaims ethanol, be concentrated into relative density and be 1.08～1.10 concentrated solution, spray drying, promptly.
By the Herb Gynostemmae Pentaphylli total glycosides of this prepared, yield is 2%～4%, and the content of Herb Gynostemmae Pentaphylli total glycosides is not less than 50%.
Herb Gynostemmae Pentaphylli total glycosides also can be by following prepared, but is not limited only to following method:
Method one: get the Herb Gynostemmae Pentaphylli medical material, add 80% alcohol reflux three times, each 2 hours, alcohol adding amount is each 10 times of amounts, filters, and filtrate recycling ethanol is to there not being the alcohol flavor, it is an amount of to add water, stir evenly, put cold, standing over night, filter, it is 1.09～1.10 concentrated solution that filtrate decompression is concentrated into relative density, spray drying, promptly.By the Herb Gynostemmae Pentaphylli total glycosides that this technology makes, yield is 5～7%, and the content of Herb Gynostemmae Pentaphylli total glycosides is not less than 40%.
Method two: get the Herb Gynostemmae Pentaphylli medical material, add 80% alcohol reflux secondary, each 3 hours, add 10 times of amounts of alcohol for the first time, 8 times of amounts for the second time, merge extractive liquid, filters, and filtrate recycling ethanol is to there not being the alcohol flavor, placement is spent the night, and filters, and decompression filtrate recycling ethanol is to the thick paste shape, and spray drying promptly.By the Herb Gynostemmae Pentaphylli total glycosides that this technology makes, yield is 6～10%, and the content of Herb Gynostemmae Pentaphylli total glycosides is not less than 30%.
Aforementioned pharmaceutical compositions can also replace Herb Gynostemmae Pentaphylli to feed intake with Herb Gynostemmae Pentaphylli total glycosides and make, and calculates with respect to the yield of medical material according to extract, and its parts by weight are: 4～100 parts of 12～300 parts of Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine or its pharmaceutically acceptable salts; Be preferably: 10～40 parts of 30～120 parts of Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine or its pharmaceutically acceptable salts; The best is: 20 parts of 60 parts of Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine or its pharmaceutically acceptable salts.
In the pharmaceutical composition of the present invention, the diisopropylamine pharmaceutically acceptable salt is preferably dichloroacetic acid salt and Ascorbate.
More than form to be by weight as proportioning, when producing, can or reduce according to the corresponding proportion increase, as large-scale production can be unit with the kilogram, or be unit with the ton, small-scale production can be unit with the gram also, weight can increase or reduce, but the constant rate of weight proportion between each composition.
The ratio of above weight proportion obtains through science screening, and for especial patient, the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.
The consumption of drug component of the present invention is groped to sum up to draw through the inventor in a large number, and each amounts of components all has better curative effect in above-mentioned weight portion scope.
Pharmaceutical composition of the present invention has antiinflammatory, antiviral, improves hepatocyte function, suppresses hepatic fibrosis, antioxidation, blood fat reducing and promotes multiple pharmacologically active such as liver steatolysis, can be used for acute, chronic hepatitis, fatty liver etc.
Pharmaceutical composition of the present invention can add one or more pharmaceutically acceptable carriers, is applied to the patient of this treatment of needs in the mode of oral or parenteral.Be used for when oral, can be made into conventional solid preparation, as tablet, capsule, soft capsule, dispersible tablet, oral liquid, granule, chewable tablet, oral cavity disintegration tablet, drop pill, slow releasing tablet, slow releasing capsule, controlled release tablet, controlled release capsule, make liquid preparation such as water or oil-suspending agent or other liquid preparation such as syrup etc.; When being used for parenteral, can be made into solution, water or the oil-suspending agent etc. of injection, as liquid drugs injection, freeze-dried powder, aseptic powder injection, transfusion etc.The preferred dosage form of this compositions is injection or oral formulations.
Pharmaceutical composition of the present invention can adopt the conventional method production in the existing pharmaceutical field, can add various pharmaceutically acceptable carriers when needing.Described carrier comprises diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc.
Pharmaceutical composition of the present invention in order to increase its dissolubility, can add solubilizing agents such as Tween-80 when making injection.Can add the isoosmotic adjusting agent that is used to regulate osmotic pressure in the transfusion, for example, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium lactate, glucose, xylitol, sorbitol and dextran etc., preferred sodium chloride or glucose.Can add excipient in the powder pin, for example, mannitol, glucose etc.
Compositions of the present invention has the following advantages:
(1) the invention provides a kind of new pharmaceutical composition that is used for the treatment of acute, chronic hepatitis, fatty liver, satisfied clinical needs.
(2) in the pharmaceutical composition of the present invention, Herb Gynostemmae Pentaphylli has good anti-hepatitis, the effect of enhance immunity, diisopropylamine dichloroacetate has good hepatoprotective effect, can promote the liver steatolysis, improve the liver function, promote impaired hepatocellular reparation, dwindle the scope of hepatic necrosis and the formation of inhibition fibrosis tissue, have the effect of good anti-hepatitis and treatment fatty liver.
(3) studies have shown that by pharmacodynamic experiment first: the chmice acute hepatic injury due to pharmaceutical composition Abensanil of the present invention, the carbon tetrachloride has significant protective effect; can significantly suppress the breeding of dhbv dna; can significantly resist the rat liver fibrosis due to the carbon tetrachloride, the experimental fatty liver rat is had significantly protect the liver, blood fat reducing and promote the fat-splitting effect of liver.Two medical instruments have synergistic function, and are evident in efficacy, produced beyond thought effect.
(4) each proportioning of pharmaceutical composition of the present invention is carried out pharmacodynamic study, drawn the optimal proportion of pharmaceutical composition of the present invention.
(5) drug combination preparation preparation technology of the present invention is simple, and mass discrepancy is little between the different batches medicine, and drug quality is uniform and stable.
(6) confirm drug combination injection safety and stability of the present invention by stability experiment.
Below further set forth the beneficial effect of medicine of the present invention by testing example.The compositions of Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine dichloroacetate is hereinafter to be referred as the JE compositions.Herb Gynostemmae Pentaphylli total glycosides used among the embodiment is all taken from embodiment 1; Used diisopropylamine dichloroacetate is commercial, contains C
8H
17O
2NCl
299.3%.
Experimental example 1 JE compositions drug combination drug efficacy study
Test sample: the gynostemma pentaphyllum total glycoside injection liquid, 2ml contains Herb Gynostemmae Pentaphylli total glycosides 60mg (being equivalent to Herb Gynostemmae Pentaphylli 2g), self-control;
The diisopropylamine dichloroacetate injection, 1ml:20mg, self-control;
The JE composite injection, the different proportionings of (Herb Gynostemmae Pentaphylli total glycosides+diisopropylamine dichloroacetate), self-control, preparation method is with reference to embodiment 2.
Laboratory animal: ICR mice, body weight 18～25g, male and female half and half.
Experimental technique: get 90 of mices, be divided into 9 groups at random, 10 every group, group sees the following form.Blank group and model group tail vein injection saline every day 20ml/kg Mus are heavy, every day 1 time, 10d continuously; The administration of administration group tail vein injection, every day 1 time, dosage sees the following form, continuously 10d.The blank group is tail vein injection 6h pneumoretroperitoneum injecting normal saline the last time.Model group and administration group tail vein injection 6h pneumoretroperitoneum injection with acetaminophen 300mg/kg Mus the last time are heavy, each group breaks end behind intraperitoneal injection of saline and acetaminophen 16h, get blood, liver, carry out the test of biochemical indicator Serum ALT (glutamate pyruvate transaminase) and hepatic tissue LPO (lipid peroxide), the results are shown in Table 1.
Conclusion: compare with the blank group, the active of model group ALT and LPO significantly raises, and difference is (P＜0.01) extremely significantly, illustrates that modeling is reliable.Compare with the blank group, active obviously reduce (P＜0.05, P＜0.01) of each proportioning group ALT of Herb Gynostemmae Pentaphylli total glycosides group, diisopropylamine dichloroacetate group and JE compositions and LPO illustrates that the hepatic injury of the equal Abensanil induced mice of each medicine has protective effect.Wherein each proportioning group better efficacy (P＜0.01) of JE compositions all is better than single Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine dichloroacetate used, and illustrates that Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine dichloroacetate two medicines share, and have synergistic function.In each proportioning group of JE compositions, the most remarkable with Herb Gynostemmae Pentaphylli total glycosides+diisopropylamine dichloroacetate (60mg+20mg) group curative effect.
The influence of table 1 JE compositions Abensanil damage murine liver tissue ALT and LPO
| Group | Proportioning (Herb Gynostemmae Pentaphylli+diisopropylamine dichloroacetate g+mg) | Mice quantity | Dosage (mg/kg) | ALT content (U/L) | LPO content (nmol/L) |
| Blank group model group Gypenosides group Diisopropylamine Dichloroacetate group JE composition group (Gypenosides+Diisopropylamine Dichloroacetate) | - - - - 30mg+40mg 60mg+20mg 60mg+40mg 120mg+10mg 120mg+20mg | 10 10 10 10 10 10 10 10 10 | - - 32 32 32 32 32 32 32 | 35.64±5.68 287.34±23.45 ◇◇ 242.15±12.42 * 224.66±13.57 * 172.46±13.58 **#△ 104.35±12.97 **##△△ 125.86±13.64 **##△ 157.62±12.47 **#△ 164.27±15.62 **#△ | 4.85±0.34 8.87±0.45 ◇◇ 7.87±0.62 * 7.31±0.44 * 6.54±0.77 **#△ 5.24±0.25 **##△△ 5.68±0.49 **##△ 6.07±0.44 **#△ 6.22±0.52 **#△ |
Compare with the blank group,
◇ ◇P＜0.01; Compare with model group,
*P＜0.05,
*P＜0.01; Compare with the Herb Gynostemmae Pentaphylli total glycosides group,
#P＜0.05,
##P＜0.01; Compare with the diisopropylamine dichloroacetate group,
△P＜0.05,
△ △P＜0.01.
Experimental example 2 JE compositionss are to carbon tetrachloride (CCl
4) cause the protective effect of chmice acute hepatic injury
Test sample: chemical pure CCl
4, Chengdu associating chemical reagent institute;
The gynostemma pentaphyllum total glycoside injection liquid, 2ml contains Herb Gynostemmae Pentaphylli total glycosides 60mg (being equivalent to Herb Gynostemmae Pentaphylli 2g), self-control;
The diisopropylamine dichloroacetate injection, 1ml:20mg, self-control;
JE composite injection (5ml contains Herb Gynostemmae Pentaphylli total glycosides+diisopropylamine dichloroacetate 60mg+20mg) is derived from embodiment 2.
Laboratory animal: ICR mice, body weight 22～27g, male and female half and half.
Experimental technique: get 70 of mices, be divided into 7 groups at random, be respectively blank group, model group, Herb Gynostemmae Pentaphylli total glycosides group, diisopropylamine dichloroacetate group, the basic, normal, high dosage group of JE compositions, 10 every group.Blank group and model group tail vein injection saline every day 20ml/kg Mus are heavy, every day 1 time, 7d continuously; The administration of administration group tail vein injection, every day 1 time, dosage sees the following form, continuously 7d.The blank group is tail vein injection 2h pneumoretroperitoneum injection Oleum Arachidis hypogaeae semen 10ml/kg the last time, the equal lumbar injection 0.12%CCl of all the other each treated animals
4Peanut oil solution 10ml/kg.Sacrificed by decapitation animal behind the 16h, the value of getting serologic test ALT, AST.After broken end is got blood, cut open the belly immediately and take out liver, spleen, inhale the liquid of dehematizing, cut off fat, mesentery, the weight of the liver of accurately weighing, spleen is calculated liver exponential sum spleen index.The results are shown in Table 2.
Table 2 JE compositions is to CCl
4Due to the influence of acute liver damage Mouse Liver, spleen index and Serum ALT, AST content
| Group | Mice quantity | Dosage (mg/kg) | Liver index (g/100g) | Spleen index (g/100g) | ALT content (U/L) | AST content (U/L) |
| Dosage group JE composition low dose group in the blank group model group Gypenosides group Diisopropylamine Dichloroacetate group JE composition high dose group JE composition | 10 10 10 10 10 10 10 | - - 32 32 32 24 16 | 6.143±1.024 8.357±0.764 ◇ 7.854±0.677 * 7.716±0.643 * 6.722±0.564 *#△ 6.994±0.658 *#△ 7.398±0.586 * | 0.587±0.135 0.781±0.097 ◇ 0.738±0.062 * 0.728±0.061 * 0.637±0.056 *#△ 0.674±0.077 *#△ 0.721±0.059 * | 38.44±6.45 257.14±25.63 ◇◇ 196.59±24.56 * 213.64±25.46 * 135.67±24.64 **#△ 149.68±25.86 **#△ 174.26±21.89 * | 238.56±32.45 416.77±35.86 ◇◇ 342.76±35.98 * 336.89±41.53 * 248.65±30.96 **#△ 285.69±30.12 **#△ 324.79±35.68 * |
Compare with the blank group
◇P＜0.05,
◇ ◇P＜0.01; Compare with model group,
*P＜0.05,
*P＜0.01; Compare with the Herb Gynostemmae Pentaphylli total glycosides group,
#P＜0.05; Compare with the diisopropylamine dichloroacetate group,
△P＜0.05.
Conclusion: CCl
4Model group Mouse Liver index, the normal control group mice numerical value of spleen index significantly increase (P＜0.05), CCl
4Model group mice serum ALT, the normal control group mice numerical value of AST value extremely significantly increase (P＜0.01), and injected in mice CCl is described
4Hepar damnification behind the peanut oil solution, the modeling success.Compare with model group, each administration group Mouse Liver index, spleen index, ALT, AST value reduce, and illustrate that each medicine is to CCl
4Due to acute liver damage protective effect is all arranged; Wherein, the middle and high dosage group of JE compositions Mouse Liver index, spleen index significantly reduce (P＜0.05), and liver, splenomegaly alleviate, and each dosage group Serum ALT of JE compositions, AST value extremely significantly reduce (P＜0.01), illustrate that the present composition is to CCl
4Due to acute liver damage obvious protective effect is arranged.Each dosage group curative effect of JE compositions all is better than single with Herb Gynostemmae Pentaphylli total glycosides and diisopropylamine dichloroacetate, illustrates that Herb Gynostemmae Pentaphylli and diisopropylamine dichloroacetate two medicines share, and have synergistic function.Wherein middle and high dosage group better efficacy (P＜0.05).
The anti-dhbv dna effect of experimental example 3 JE compositionss
Test sample: acyclovir, Xinxiang Pharmacy stock Co., Ltd;
Herb Gynostemmae Pentaphylli total glycosides, self-control;
Diisopropylamine dichloroacetate, commercial;
JE compositions sheet (every contains Herb Gynostemmae Pentaphylli total glycosides+diisopropylamine dichloroacetate 60mg+20mg) is derived from embodiment 6.
DHBV (DHB) positive serum, microbiology teaching and research room of Medical Center of Fudan University.
Laboratory animal: commercially available 1 age in days Beijing duck;
Experimental technique:
The animal model Beijing duck is got blood through sufficient intravenous injection 0.2mlDHBV positive serum behind the 7d, separation of serum, and-20 ℃ of preservations are to be checked.
Drug therapy filters out 42 of the positive ducks that infect successfully, is divided into 7 groups at random, 6 every group, is respectively blank group, positive controls, Herb Gynostemmae Pentaphylli total glycosides group, diisopropylamine dichloroacetate group, the basic, normal, high dosage group of JE compositions, 6 every group.The blank group is irritated stomach normal saline 20ml/kg every day, every day 2 times, 14d continuously; Administration group gastric infusion, every day 2 times, dosage sees the following form, continuously 14d.Positive drug is pressed 100mg/kg with acyclovir (ACV) and is irritated stomach, 2 times/d, 2 weeks of administration as the treatment matched group.Be respectively applied for (1d), the 7th day (T of medication before the medicine
7), the 14th day (T of medication
14) and drug withdrawal after the 7th day (P
7).Get blood from duck lower limb shin vein, separation of serum ,-20 ℃ of preservations are to be checked.Adopt DHBV-DNA Dot Blot method, with hybridization spot absorbance (A) as specimen DHBV-DNA level value.The results are shown in Table 3.
Table 3 JE compositions is to the inhibitory action of DHBV-DNA
| Group | Duck quantity | Dosage (mg/kg) | DHBV-DNA titre before the treatment | Treatment back 7d DHBV-DNA titre | Treatment back 14d DHBV-DNA titre | 7d DHBV-DNA titre after the drug withdrawal |
| Dosage group JE composition low dose group in the blank group positive controls gynostemma pentaphyllum total former times group Diisopropylamine Dichloroacetate group JE composition high dose group JE composition | 6 6 6 6 6 6 6 | - - 32 32 32 24 16 | 1.67±0.05 1.65±0.04 1.66±0.04 1.68±0.09 1.67±0.08 1.65±0.07 1.66±0.09 | 1.64±0.06 0.82±0.06 ◇◇@@ 1.40±0.08 1.35±0.05 1.04±0.06 ◇@ 1.16±0.08 ◇@ 1.30±0.06 | 1.66±0.04 0.70±0.07 ◇◇@@ 1.30±0.07 ◇@ 1.19±0.08 ◇@ 0.78±0.06 ◇◇@@ 0.87±0.05 ◇◇@@ 1.03±0.05 ◇@ | 1.67±0.06 1.63±0.06 1.58±0.06 1.61±0.07 1.06±0.04 ◇@ 1.17±0.10 ◇@ 1.31±0.05 |
Annotate: compare with the blank group
◇P＜0.05,
◇ ◇P＜0.01; With compare before the administration
@P＜0.05,
@@P＜0.01.
Conclusion: positive control (acyclovir) group after administration the 7th day and the 14th day, with before the administration and with the blank group relatively, difference has utmost point significance (P＜0.01), but significantly rising again after the drug withdrawal does not have significance (P＞0.05) with comparing difference before the administration.Various dose JE compositions all has inhibitory action to DHBV, and does not have knock-on after the drug withdrawal, and wherein middle and high dosage group inhibitory action is more obvious.Each administration group curative effect of JE compositions all is better than single with Herb Gynostemmae Pentaphylli total glycosides and diisopropylamine dichloroacetate, illustrates that Herb Gynostemmae Pentaphylli total glycosides and diisopropylamine dichloroacetate two medicines share, and have synergistic function.
The Hepar Mus fibrosis effect of the experimental example 4 JE compositions Chinese People's Anti-Japanese Military and Political College
Test sample: chemical pure CCl
4, Chengdu associating chemical reagent institute;
The gynostemma pentaphyllum total glycoside injection liquid, 2ml contains Herb Gynostemmae Pentaphylli total glycosides 60mg (being equivalent to Herb Gynostemmae Pentaphylli 2g), self-control;
The diisopropylamine dichloroacetate injection, 1ml:20mg, self-control;
JE composite injection (5ml contains Herb Gynostemmae Pentaphylli total glycosides+diisopropylamine dichloroacetate 60mg+20mg) is derived from embodiment 2.
Laboratory animal: the Wistar rat, body weight 180～230g, male.
Experimental technique: get 10 of healthy rats, subcutaneous injection Oleum Arachidis hypogaeae semen 3ml/kg, every day 1 time, totally 10 weeks, group in contrast.The Liver Fibrosis Model group is used 40%CCl
4Peanut oil solution is pressed the 3ml/kg subcutaneous injection, 2 times weekly, in totally 8 weeks, induces Liver Fibrosis Model.Get 60 of Liver Fibrosis Model rats, be divided into 6 groups at random, be respectively model group, Herb Gynostemmae Pentaphylli total glycosides group, diisopropylamine dichloroacetate group, the basic, normal, high dosage group of JE composite injection, 10 every group.Except that the normal control group, all the other each groups continue with 40%CCl
4Peanut oil solution 3ml/kg subcutaneous injection, every day 1 time.Herb Gynostemmae Pentaphylli total glycosides group, diisopropylamine dichloroacetate group, tiopronin group, the basic, normal, high dosage group of JE composite injection be the intraperitoneal injection relative medicine simultaneously, and dosage sees the following form.Continue 2 weeks of administration.Slaughter rat after 10 weeks, blood 2ml gets in the sterile working, separation of serum, and-20 ℃ of preservations detect hepatic fibrosis index with radioimmunology: hyaluronic acid (HA) and laminin (LN); Detect glutamate pyruvate transaminase (ALT) and glutamic oxaloacetic transaminase, GOT (AST) with biochemical process, adopt automatic clinical chemistry analyzer to detect.The results are shown in Table 4.
Table 4 JE compositions is to CCl
4Due to the influence of serological index of hepatic fibrosis rats
| Group | Size of animal | Dosage (mg/kg) | ALT (U/L) | AST (U/L) | LN (μg/L) | HA (μg/L) |
| Dosage group JE composition low dose group in the Normal group model group Gypenosides group Diisopropylamine Dichloroacetate group JE composition high dose group JE composition | 10 10 10 10 10 10 10 | - - 32 32 32 24 16 | 37.64±5.23 273.52±31.47 ◇◇◇ 212.37±23.87 * 187.65±21.98 * 125.48±24.78 **#△ 149.66±23.52 **# 185.47±20.86 * | 242.56±30.78 425.67±46.51 ◇◇◇ 352.46±31.24 * 319.47±32.97 * 243.26±27.69 **#△ 284.77±24.35 **# 311.58±26.96 * | 44.96±15.48 116.97±21.44 ◇◇◇ 90.54±14.23 * 83.56±14.36 * 55.48±14.38 **#△ 69.87±18.26 **# 74.32±13.58 * | 137.98±17.84 348.56±35.47 ◇◇◇ 252.37±24.36 * 235.61±30.54 * 146.56±24.54 **#△ 179.67±21.54 **# 219.67±29.87 * |
Compare with the normal control group
◇ ◇ ◇P＜0.001; Compare with model group,
*P＜0.05,
*P＜0.01; Compare with the Herb Gynostemmae Pentaphylli total glycosides group,
#P＜0.05; Compare with the diisopropylamine dichloroacetate group,
△P＜0.05.
Conclusion: compare with the normal control group, model group rat blood serum ALT, AST, HA, LN content have utmost point significant difference (P＜0.001), illustrate that model is reliable.Herb Gynostemmae Pentaphylli, diisopropylamine dichloroacetate and JE combination treatment heptic fibrosis rat blood serum ALT and AST all are lower than model group, difference has significance (P＜0.05 or P＜0.01), and prompting Herb Gynostemmae Pentaphylli, diisopropylamine dichloroacetate and JE compositions have the effect of falling enzyme and liver function protecting; Serum HA and LN level all significantly are lower than model group behind Herb Gynostemmae Pentaphylli, diisopropylamine dichloroacetate and the JE combination treatment, difference has significance (P＜0.05 or P＜0.01), prompting Herb Gynostemmae Pentaphylli, JE compositions all can be improved the hepatic fibrosis serological index, have the effect of anti-hepatic fibrosis.JE compositions group curative effect is better than single with Herb Gynostemmae Pentaphylli, diisopropylamine dichloroacetate, and prompting Herb Gynostemmae Pentaphylli total glycosides and diisopropylamine dichloroacetate two medicines share, and synergistic function is arranged.Wherein, JE compositions high dose group better efficacy (P＜0.05).
Test example 5 JE compositionss are to the effect of rat experiment fatty liver
Experimental animal; The Wistar rat, male and female half and half, body weight 208～230g.
Test sample: Herb Gynostemmae Pentaphylli total glycosides, self-control;
Diisopropylamine dichloroacetate, commercial;
JE compositions sheet (every contains Herb Gynostemmae Pentaphylli total glycosides+diisopropylamine dichloroacetate 60mg+20mg) is derived from embodiment 6.
Test method: rat, behind the every index of liver function, cholesterol and the triglyceride levels, build hyperlipidemia model before the survey medicine.Except that the blank group gives the normal diet, all the other each groups all give high lipid food (containing Adeps Sus domestica 20%, cholesterol 10%, cholate 0.5%, thiouracil 0.2%), and feed is after 7 weeks continuously, survey the every index of liver function, serum cholesterol and triglyceride levels, determine that hyperlipidemia model builds up.60 of delivery type rats are divided into 6 groups at random, are respectively the basic, normal, high dosage group of model group, Herb Gynostemmae Pentaphylli total glycosides group, diisopropylamine dichloroacetate group and JE compositions, 10 every group.Continue to raise high lipid food, except that model group, other each group is gastric infusion Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine dichloroacetate and JE compositions respectively, every day, gastric infusion was 1 time, gastric infusion pneumoretroperitoneum injection in 10 days thioacetamide 450mg/kg (causing liver function injury), continue to give laboratory sample then, after giving thioacetamide the 4th day with animal with the smooth anesthesia of horse traction, ventral aorta blood sampling.Centrifugalize serum detects liver function AST (glutamic oxaloacetic transaminase, GOT), ALT (glutamate pyruvate transaminase), ALP (alkali phosphatase), HDL (high density lipoprotein), LDL (low density lipoprotein, LDL); Other gets liver 400mg, and (normal heptane: 4ml homogenate 4: 7 v/v of isopropyl alcohol), lipid is extracted in concussion, gets supernatant after the centrifugation and measures liver TG and CHO to add the lipid extracting solution.Serum biochemistry is learned and the liver lipid assay all adopts automatic biochemistry analyzer to measure.The results are shown in Table 5 and table 6.
Table 5 JE compositions is to the influence of experimental fatty liver rats'liver functional parameter
| Group | Size of animal | Dosage (mg/kg) | Liver function index | ||
| AST | ALT | ALP | |||
| Dosage group JE composition low dose group in the Normal group model group Gypenosides group Diisopropylamine Dichloroacetate group JE composition high dose group JE composition | 10 - 10 10 10 10 10 | - - 32 32 32 24 16 | 238±49 918±254 ◇◇◇ 685±186 * 654±172 ** 462±165 **##△ 572±147 **#△ 614±135 ** | 55±8 1157±765 ◇◇◇ 348±152 ** 312±139 ** 182±105 **##△ 224±127 **##△ 256±116 **# | 228±59 662±454 ◇◇◇ 543±357 * 456±329 * 335±304 **##△ 389±278 **# 413±241 **# |
Compare with the normal control group
◇ ◇ ◇P＜0.001; Compare with model group,
*P＜0.05,
*P＜0.01; Compare with the Herb Gynostemmae Pentaphylli total glycosides group,
#P＜0.05,
##P＜0.05; Compare with the diisopropylamine dichloroacetate group,
△P＜0.05.
Table 6 JE compositions is to the influence of experimental fatty liver blood fat and liver fat index
| Group | Size of animal | Dosage (mg/kg) | Blood lipids index | The liver fat index | ||
| HDL | LDL | TG | CHO | |||
| Dosage group JE composition low dose group in the Normal group model group Gypenosides group Diisopropylamine Dichloroacetate group JE composition high dose group JE composition | 10 - 10 10 10 10 10 | - - 32 32 32 24 16 | 0.6±0.1 2.1±0.7 ◇◇ 1.6±0.6 1.3±0.5 * 0.8±0.2 **#△ 1.0±0.3 **#△ 1.1±0.5 ** | 0.3±0.1 1.6±0.7 ◇◇ 1.3±0.6 1.1±0.4 0.5±0.3 **#△ 0.7±0.5 *#△ 0.9±0.4 * | 2.6±0.8 4.4±0.9 ◇◇ 4.3±1.2 3.7±0.7 * 2.8±0.4 **#△ 3.2±0.5 **#△ 3.4±0.8 ** | 1.2±0.3 5.3±1.8 ◇◇ 4.7±1.3 4.3±1.5 * 2.2±0.6 **##△△ 2.8±0.4 **#△ 3.5±0.7 **# |
Compare with the normal control group
◇ ◇P＜0.001; Compare with model group,
*P＜0.05,
*P＜0.01; Compare with the Herb Gynostemmae Pentaphylli total glycosides group,
#P＜0.05,
##P＜0.01; Compare with the diisopropylamine dichloroacetate group,
△P＜0.05,
△ △P＜0.01.
Conclusion: after adding the lumbar injection thioacetamide to high fat diet, as seen model group AST, ALT, ALP are than normal group extremely significantly raise (P＜0.001), serum hdl, LDL extremely significantly raise (P＜0.01), and liver TG and CHO significantly raise (P＜0.01), illustrate that model is reliable.After the administration of JE compositions, AST, ALT, ALP significantly reduce (P＜0.01) than model group, show that the JE compositions has the effect of alt-reducing and liver-protecting, curative effect is better than single with Herb Gynostemmae Pentaphylli total glycosides and single diisopropylamine dichloroacetate of using, show that Herb Gynostemmae Pentaphylli and diisopropylamine dichloroacetate share, synergistic function is arranged, wherein middle and high dosage group better efficacy (P＜0.01 and P＜0.05); After the administration of JE compositions, serum hdl, LDL significantly reduce (P＜0.01 and P＜0.05) than model group, liver TG and CHO significantly reduce (P＜0.01) than model group, prompting JE compositions has blood fat reducing and promotes the fat-splitting effect of liver, curative effect is better than single with Herb Gynostemmae Pentaphylli total glycosides and single diisopropylamine dichloroacetate of using, show that Herb Gynostemmae Pentaphylli total glycosides and diisopropylamine dichloroacetate share, synergistic function is arranged, wherein middle and high dosage group better efficacy (P＜0.01 and P＜0.05)
Experimental example 6 JE composite injection stability experiments
Test sample: the JE composite injection, dosage form: liquid drugs injection, specification: 5ml derives from embodiment 2.
Investigation project: character, pH value, clarity.
Long-time stability experimental technique and result: the JE composite injection is put under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% and placed 6 months, 12 months, every index has no significant change, and experimental result shows that the long-term placement of JE composite injection is basicly stable.
4, the specific embodiment
The specific embodiment of form is described in further detail foregoing of the present invention by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.The adjuvant of each dosage form can be replaced with acceptable accessories in following examples, perhaps reduces, increases.Herb Gynostemmae Pentaphylli total glycosides used among the embodiment 2～8 is all taken from embodiment 1.
The preparation of embodiment 1 Herb Gynostemmae Pentaphylli total glycosides
Get the Herb Gynostemmae Pentaphylli medical material, add 75% alcohol reflux secondary, each 2 hours, filter, flow liquid reclaims ethanol to there not being the alcohol flavor, adds water and makes into the solution that every 1ml is equivalent to 2g crude drug amount, stirs evenly, put coldly, standing over night filters, the macroporous resin column of filtrate by having handled well, earlier with the water of 2 times of column volumes towards post, discard water liquid, 60% ethanol of 3 times of column volumes of reuse carries out eluting, collects eluent, reclaims ethanol, be concentrated into relative density and be 1.08～1.10 concentrated solution, spray drying, promptly.
Make three batches of Herb Gynostemmae Pentaphylli extracts respectively, extract yield and content see Table 7.
Differentiate
Get Herb Gynostemmae Pentaphylli total glycosides 0.5g, add dissolve with methanol, make the solution that every 1ml contains 10mg, as the broad liquid of test sample.Other gets gypenoside-A reference substance, adds dissolve with methanol, makes the solution that every 1ml contains 1mg, in contrast product solution.The thin layer chromatography experiment, draw each 2 μ l of need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, (15: 40: 22: 10) lower floor's solution of placing below 10 ℃ was developing solvent, launched with chloroform-ethyl acetate-methanol-water, exhibition is apart from 12cm, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear that hot blast blows to the speckle colour developing, inspects under daylight and under the ultra-violet lamp (365nm).In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle and the fluorescence speckle of same color respectively.
Assay
The preparation precision of reference substance solution takes by weighing in that 3 hours gypenoside of 60 ℃ of drying under reduced pressure-the A reference substance is an amount of, adds dissolve with methanol, makes the solution that every 1ml contains 2mg.
The preparation precision of need testing solution takes by weighing this product 50mg, adds dissolve with methanol, makes the solution that every 1ml contains 2mg.
Accurate reference substance solution and each the 100 μ l of need testing solution of drawing of algoscopy, put respectively in the 15ml tool plug test tube, the accurate mixed liquor 2ml that contains 5% vanillin glacial acetic acid solution and perchloric acid (2: 8) that adds new preparation, shake up, close plug, put in 60 ℃ of water-baths and heated 15 minutes, take out, put into frozen water cooling 2 minutes immediately, the accurate glacial acetic acid 10ml that adds, shake up, make blank with reagent,, measure trap at 555 ± 5nm wavelength place according to spectrophotography (appendix of Chinese Pharmacopoeia version in 2000) test, calculate, promptly.
This product is pressed dry product and is calculated, and contains Herb Gynostemmae Pentaphylli total glycosides with gypenoside-A (C
53H
90O
21) meter, must not be less than 50.0%.
The yield of table 7 Herb Gynostemmae Pentaphylli total glycosides and content
| Batch | Medical material weight (kg) | Extract weight (kg) | Extract yield (%) | Total saponin content (%) |
| 123 is average | 20 20 20 20 | 0.532 0.618 0.650 0.600 | 2.66 3.09 3.25 3.00 | 54.8 65.4 62.2 60.8 |
The preparation of embodiment 2 JE compositions aqueous injection
Prescription:
Herb Gynostemmae Pentaphylli total glycosides 60g
Diisopropylamine dichloroacetate 20g
Gluconic acid sodium salt 19g
Polyoxyethylene sorbitan monoleate 50g
Water for injection adds to 5000ml
Prepare 1000 altogether
Preparation technology:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) Herb Gynostemmae Pentaphylli total glycosides is added in the water for injection of dosing amount 30% the heated and stirred dissolving fully.Diisopropylamine dichloroacetate and gluconic acid sodium salt are added a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.
3) merge above-mentioned solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.45um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) with the solution sealing by fusing in glass ampule.
9) 100 ℃ of flowing steam sterilizations are 30 minutes.
10) while hot sample being put into 0.01% methylene blue solution hunts leak.
11) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 3 JE composition powder injections
Prescription:
Herb Gynostemmae Pentaphylli total glycosides 60g
Diisopropylamine dichloroacetate 20g
Gluconic acid sodium salt 19g
Polyoxyethylene sorbitan monoleate 20g
Mannitol 400g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
Preparation technology:
1) vessel of at first dosing being used and antibiotic glass bottle, plug etc. carry out aseptic process.
2) take by weighing supplementary material according to recipe quantity.
3) Herb Gynostemmae Pentaphylli total glycosides is added in the water for injection of dosing amount 30% the heated and stirred dissolving fully.Diisopropylamine dichloroacetate and gluconic acid sodium salt are added a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.Merge above-mentioned solution, add sterile water for injection to full dose.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.22um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) be sub-packed in the antibiotic glass bottle half tamponade.Sample is put into the freeze dryer lyophilization.Pre-freeze-45 ℃ 5 hours, low-temperature vacuum drying-45 ℃～0 ℃ 20 hours was warming up to 25 ℃ of vacuum dryings 3 hours then.
9) lyophilizing finishes, and lid is rolled in tamponade.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 4 JE compositions sodium chloride transfusion
Prescription:
Herb Gynostemmae Pentaphylli total glycosides 60g
Diisopropylamine dichloroacetate 20g
Gluconic acid sodium salt 19g
Polyoxyethylene sorbitan monoleate 20g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Preparation technology:
1) handles the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) Herb Gynostemmae Pentaphylli total glycosides is added in the water for injection of dosing amount 30% the heated and stirred dissolving fully.Diisopropylamine dichloroacetate and gluconic acid sodium salt are added a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.With sodium chloride with an amount of water for injection dissolving fully, merge above-mentioned solution, benefit adds to the full amount of water for injection.
3) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
4) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
5) through the microporous filter membrane fine straining of 0.45um.
6) clarity of inspection solution, the semi-finished product chemical examination.
7) fill is in the infusion bottle of 100ml.
8) 115 ℃ of pressure sterilizings are 30 minutes.
9) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 5 JE compositions glucose infusion liquids
Prescription:
Herb Gynostemmae Pentaphylli total glycosides 60g
Diisopropylamine dichloroacetate 20g
Gluconic acid sodium salt 19g
Polyoxyethylene sorbitan monoleate 20g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Preparation technology:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) Herb Gynostemmae Pentaphylli total glycosides is added in the water for injection of dosing amount 30% the heated and stirred dissolving fully.Diisopropylamine dichloroacetate and gluconic acid sodium salt are added a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.Merge above-mentioned solution, benefit adds to the full amount of water for injection.Glucose is complete with the water for injection dissolving of dosing amount 40%, heated and boiled 15 minutes.
3) merge above-mentioned solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.45um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) fill is in the infusion bottle of 100ml.
9) 115 ℃ of pressure sterilizings are 30 minutes.
10) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 6 JE composition tablets
Prescription:
Herb Gynostemmae Pentaphylli total glycosides 60g
Diisopropylamine dichloroacetate 20g
Calcium gluconate 19.5g
Starch 50.0g
Microcrystalline Cellulose 50.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 5.0g
Carboxymethylstach sodium 10.0g
Prepare 1000 altogether
Preparation technology:
1) it is standby Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine dichloroacetate and calcium gluconate pulverize separately to be crossed 100 mesh sieves.
2) take by weighing supplementary material according to recipe quantity.
3) hypromellose 2% the aqueous solution made soluble in water is standby.
4) with Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine dichloroacetate, calcium gluconate, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is dried under 60 ℃ condition.
7) dry good granule adds magnesium stearate and carboxymethylstach sodium, crosses 18 mesh sieve granulate, mix homogeneously.
8) sampling, the semi-finished product chemical examination.
9) the sheet weight sheet of determining according to chemical examination.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 7 JE composition capsules
Prescription:
Herb Gynostemmae Pentaphylli total glycosides 60g
Diisopropylamine dichloroacetate 20g
Calcium gluconate 19.5g
Starch 20.0g
Microcrystalline Cellulose 60.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 5.0g
Prepare 1000 altogether
Preparation technology:
1) it is standby Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine dichloroacetate and calcium gluconate pulverize separately to be crossed 100 mesh sieves.
2) take by weighing supplementary material according to recipe quantity.
3) hypromellose 2% the aqueous solution made soluble in water is standby.
4) with Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine dichloroacetate, calcium gluconate, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is dried under 60 ℃ condition.
7) dry good granule adds magnesium stearate, crosses 18 mesh sieve granulate, mix homogeneously.
8) sampling, the semi-finished product chemical examination.
9) loading amount of determining according to chemical examination incapsulates.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 8 JE composition granules
Prescription:
Herb Gynostemmae Pentaphylli total glycosides 60g
Diisopropylamine dichloroacetate 20g
Calcium gluconate 19.5g
Icing Sugar 600.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Preparation technology:
1) it is standby sucrose to be pulverized 100 mesh sieves.It is standby that Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine dichloroacetate and calcium gluconate pulverize separately are crossed 100 mesh sieves.
2) take by weighing supplementary material according to recipe quantity.
3) the method mix homogeneously that Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine dichloroacetate, calcium gluconate and Icing Sugar are progressively increased with equivalent, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and makes suitable soft material,
4) cross 20 mesh sieve system granules.
5) granule is dried under 60 ℃ condition.
6) dried granule is crossed 18 mesh sieve granulate.
7) sampling, the content of principal agent is determined loading amount in the semi-finished product chemical examination granule.
8) packing, finished product is examined entirely, the packing warehouse-in.
Claims (10)
1. pharmaceutical composition is characterized in that this pharmaceutical composition mainly made by following bulk drugs: 4～100 parts of 400～10000 parts of Herb Gynostemmae Pentaphylli, diisopropylamine or its pharmaceutically acceptable salts.
2. pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition mainly made by following bulk drugs: 10～40 parts of 1000～4000 parts of Herb Gynostemmae Pentaphylli, diisopropylamine or its pharmaceutically acceptable salts.
3. pharmaceutical composition as claimed in claim 2 is characterized in that this pharmaceutical composition mainly made by following bulk drugs: 20 parts of 2000 parts of Herb Gynostemmae Pentaphylli, diisopropylamine or its pharmaceutically acceptable salts.
4. as the described arbitrary preparation of drug combination method of claim 1～3, it is characterized in that described Herb Gynostemmae Pentaphylli can obtain its extract through extracting processing with The suitable solvent, extract is made various preparations with diisopropylamine or its pharmaceutically acceptable salt, pharmaceutic adjuvant hybrid process again.
5. preparation of drug combination method as claimed in claim 4 is characterized in that main effective ingredient contained in the Herb Gynostemmae Pentaphylli extract is a Herb Gynostemmae Pentaphylli total glycosides, and its content is not less than 30%.
6. pharmaceutical composition as claimed in claim 1 is characterized in that, said composition also can mainly be made by following bulk drugs: Herb Gynostemmae Pentaphylli total glycosides and diisopropylamine or its pharmaceutically acceptable salt; Its weight proportion is: 4～100 parts of 12～300 parts of Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine or its pharmaceutically acceptable salts.
7. pharmaceutical composition as claimed in claim 6 is characterized in that its weight proportion is: 10～40 parts of 30～120 parts of Herb Gynostemmae Pentaphylli total glycosides, diisopropylamine or its pharmaceutically acceptable salts.
8. as claim 6,7 described arbitrary pharmaceutical compositions, it is characterized in that the content of described Herb Gynostemmae Pentaphylli total glycosides is not less than 30%.
9. as claim 1,2,3,6,7 described arbitrary pharmaceutical compositions, it is characterized in that described diisopropylamine pharmaceutically acceptable salt is dichloroacetic acid salt or Ascorbate.
10. as claim 1,2,3,6,7 described arbitrary pharmaceutical compositions, it is characterized in that this pharmaceutical composition can make clinically any or pharmaceutically acceptable dosage form.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2005101311206A CN1989992B (en) | 2005-12-26 | 2005-12-26 | Compound recipe pharmaceutical composition of traditional Chinese medicine and Western medicine for treating liver diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2005101311206A CN1989992B (en) | 2005-12-26 | 2005-12-26 | Compound recipe pharmaceutical composition of traditional Chinese medicine and Western medicine for treating liver diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1989992A true CN1989992A (en) | 2007-07-04 |
| CN1989992B CN1989992B (en) | 2010-08-11 |
Family
ID=38212673
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2005101311206A Expired - Fee Related CN1989992B (en) | 2005-12-26 | 2005-12-26 | Compound recipe pharmaceutical composition of traditional Chinese medicine and Western medicine for treating liver diseases |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1989992B (en) |
-
2005
- 2005-12-26 CN CN2005101311206A patent/CN1989992B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1989992B (en) | 2010-08-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1876040A (en) | Pharmaceutical composition for treating hepatitis, its preparation process and quality control method | |
| CN1245198C (en) | Chinese medicine composition for treating diabetes and its preparing method | |
| CN101049324A (en) | Composition of medication prepared from ginkgo leaves and puerarin | |
| CN101062084A (en) | Anti-hepatitis medical combination | |
| CN1839932A (en) | Red sage root formulation for venous injection and preparation process thereof | |
| CN101032503A (en) | Effective elements of Chinese traditional medicine combination for curing cardiovascular disease and the quality control method | |
| CN1236319A (en) | Pharmaceutical composition containing a mixed extract of phellodondron amurense amurense ruprecht cortex and patrinia scabiosaefolia fish for treatment of hepatitis C | |
| CN100341492C (en) | Ginseng-astragalus blood-sugar lowering soft capsule, and its preparing and detecting method | |
| CN101049293A (en) | Medication composition of acetyl cysteine or its pharmaceutical salt and asarin | |
| CN1947749A (en) | Medicine composition contg. Poria cocos and Touhualiao (polygonaceae) | |
| CN101041004A (en) | Novel antineoplastic compound medicine | |
| CN1709436A (en) | Yinzhihuang tablet of oriental wormwood, cape jasmine and baicalin, and its preparing and detecting method | |
| CN1989992A (en) | Compound recipe pharmaceutical composition of traditional Chinese medicine and Western medicine for treating liver diseases | |
| CN1931233A (en) | Medicine composition of red sage and epimedium for treating cardiac and cerebral vascular diseases | |
| CN1253170C (en) | Chinese medicine preparation for treating hepatitis and its preparing and detecting method | |
| CN1566136A (en) | Pasqueflower notoginsenosides and extraction method, medicinal uses and pharmaceutical preparation thereof | |
| CN101040934A (en) | Medicine compound made of haw leaf and rhodiola | |
| CN1954870A (en) | Medical composite prepared by sarcandra and oldenlandia | |
| CN1939412A (en) | Medicinal composition with dauricine and houttuynin sodium | |
| CN101040886A (en) | Medicine compound of erigeron breviscapus and tanshinone IIA sodium sulfoacid | |
| CN1923228A (en) | Pharmaceutical composition comprising notoginseng extract, Danshen extract and ligustrazine | |
| CN100341536C (en) | Yinzhihuang dispersion tablet of oriental wormwood, cape jasmine and baicalin, and its preparing and detecting method | |
| CN1336233A (en) | Hepatitis B treating medicine | |
| CN1853701A (en) | Effective part of Sang Medicine and preparation thereof | |
| CN101049294A (en) | Medication composition in use for treating liver disease |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| ASS | Succession or assignment of patent right |
Owner name: XUAN ZHU SHANDONG MEDICINE TECHNOLOGY CO. Free format text: FORMER OWNER: HUANG ZHENHUA Effective date: 20080530 |
|
| C10 | Entry into substantive examination | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20080530 Address after: Tianchen Avenue Ji'nan High-tech Development Zone in Shandong province No. 2518 post encoding: 250101 Applicant after: Shandong Xuanzhu Medical Technology Co., Ltd. Address before: Post encoding No. 2518 block A, Tianchen Avenue Ji'nan High-tech Development Zone in Shandong Province: 250101 Applicant before: Huang Zhenhua |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: HAIAN SUSHI TECHNOLOGY TRANSFORMATION CENTER CO., Free format text: FORMER OWNER: SHANDONG XUANZHU MEDICAL TECHNOLOGY CO., LTD. Effective date: 20131008 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 250101 JINAN, SHANDONG PROVINCE TO: 226601 NANTONG, JIANGSU PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20131008 Address after: 226601 No. 8 Yingbin Road, software park, Haian County, Jiangsu Province Patentee after: Haian Su Fu Technology Transfer Center Co., Ltd. Address before: Tianchen Avenue in Ji'nan high tech Development Zone of Shandong province 250101 City No. 2518 Patentee before: Shandong Xuanzhu Medical Technology Co., Ltd. |
|
| ASS | Succession or assignment of patent right |
Owner name: JIANGSU UNIVERSITY OF TECHNOLOGY Free format text: FORMER OWNER: HAIAN SUSHI TECHNOLOGY TRANSFORMATION CENTER CO., LTD. Effective date: 20150113 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 226601 NANTONG, JIANGSU PROVINCE TO: 213001 CHANGZHOU, JIANGSU PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20150113 Address after: 213001 Changzhou Province in the Clock Tower District, Jiangsu, Wu Road, No. 1801 Patentee after: Jiangsu University of Technology Address before: 226601 No. 8 Yingbin Road, software park, Haian County, Jiangsu Province Patentee before: Haian Su Fu Technology Transfer Center Co., Ltd. |
|
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20100811 Termination date: 20151226 |
|
| EXPY | Termination of patent right or utility model |