CN1911954A - 带氨基酸的甘草酸衍生物、其制备方法及含有它们的药物组合物 - Google Patents
带氨基酸的甘草酸衍生物、其制备方法及含有它们的药物组合物 Download PDFInfo
- Publication number
- CN1911954A CN1911954A CN 200610127322 CN200610127322A CN1911954A CN 1911954 A CN1911954 A CN 1911954A CN 200610127322 CN200610127322 CN 200610127322 CN 200610127322 A CN200610127322 A CN 200610127322A CN 1911954 A CN1911954 A CN 1911954A
- Authority
- CN
- China
- Prior art keywords
- potenlini
- acid
- amino acid
- pharmaceutical salts
- compound
- 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.)
- Pending
Links
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical class O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 title claims abstract description 84
- 150000001413 amino acids Chemical class 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- 239000000203 mixture Substances 0.000 title claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 22
- 206010067125 Liver injury Diseases 0.000 claims abstract description 14
- 238000002347 injection Methods 0.000 claims abstract description 10
- 239000007924 injection Substances 0.000 claims abstract description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 54
- 235000001014 amino acid Nutrition 0.000 claims description 48
- 229940024606 amino acid Drugs 0.000 claims description 48
- 239000011734 sodium Substances 0.000 claims description 40
- 150000001875 compounds Chemical class 0.000 claims description 25
- 239000002253 acid Substances 0.000 claims description 19
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 18
- 239000000047 product Substances 0.000 claims description 18
- 229930182817 methionine Natural products 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 16
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 16
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 15
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 15
- 239000012346 acetyl chloride Substances 0.000 claims description 15
- 235000003704 aspartic acid Nutrition 0.000 claims description 14
- 239000000843 powder Substances 0.000 claims description 14
- -1 Potenlini compound Chemical class 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 13
- 159000000000 sodium salts Chemical class 0.000 claims description 11
- 238000009833 condensation Methods 0.000 claims description 9
- 230000005494 condensation Effects 0.000 claims description 9
- 230000007062 hydrolysis Effects 0.000 claims description 9
- 238000006460 hydrolysis reaction Methods 0.000 claims description 9
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 8
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 claims description 7
- 231100000012 chronic liver injury Toxicity 0.000 claims description 7
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 claims description 7
- 239000001685 glycyrrhizic acid Substances 0.000 claims description 7
- 229960004949 glycyrrhizic acid Drugs 0.000 claims description 7
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 claims description 7
- 235000019410 glycyrrhizin Nutrition 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 239000012190 activator Substances 0.000 claims description 6
- 239000012670 alkaline solution Substances 0.000 claims description 6
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 239000007810 chemical reaction solvent Substances 0.000 claims description 6
- 239000012467 final product Substances 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 6
- 231100000439 acute liver injury Toxicity 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 150000003863 ammonium salts Chemical class 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 2
- 239000004475 Arginine Substances 0.000 claims description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Chemical compound OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 claims description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 2
- XUYPXLNMDZIRQH-LURJTMIESA-N N-acetyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC(C)=O XUYPXLNMDZIRQH-LURJTMIESA-N 0.000 claims description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 2
- 239000004473 Threonine Substances 0.000 claims description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000000470 constituent Substances 0.000 claims description 2
- 229960002989 glutamic acid Drugs 0.000 claims description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 2
- 229960000310 isoleucine Drugs 0.000 claims description 2
- 159000000003 magnesium salts Chemical class 0.000 claims description 2
- 229960003104 ornithine Drugs 0.000 claims description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- 239000007901 soft capsule Substances 0.000 claims description 2
- 239000000375 suspending agent Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims 1
- 230000032050 esterification Effects 0.000 claims 1
- 238000005886 esterification reaction Methods 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 8
- 231100000419 toxicity Toxicity 0.000 abstract description 5
- 230000001988 toxicity Effects 0.000 abstract description 5
- 210000004185 liver Anatomy 0.000 abstract description 4
- 231100000234 hepatic damage Toxicity 0.000 abstract description 3
- 230000008818 liver damage Effects 0.000 abstract description 3
- 230000000144 pharmacologic effect Effects 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 108090000340 Transaminases Proteins 0.000 description 10
- 239000002504 physiological saline solution Substances 0.000 description 10
- 102000014898 transaminase activity proteins Human genes 0.000 description 10
- ILRKKHJEINIICQ-OOFFSTKBSA-N Monoammonium glycyrrhizinate Chemical compound N.O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O ILRKKHJEINIICQ-OOFFSTKBSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 150000001510 aspartic acids Chemical class 0.000 description 6
- BYHXBBOSJKPUJL-BYPYZUCNSA-N dimethyl (2s)-2-aminobutanedioate Chemical compound COC(=O)C[C@H](N)C(=O)OC BYHXBBOSJKPUJL-BYPYZUCNSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 6
- 101710092506 Aspartate aminotransferase Proteins 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 101710101107 Probable aspartate aminotransferase Proteins 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 239000002574 poison Substances 0.000 description 5
- 231100000614 poison Toxicity 0.000 description 5
- 231100000572 poisoning Toxicity 0.000 description 5
- 230000000607 poisoning effect Effects 0.000 description 5
- 102000009027 Albumins Human genes 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 4
- 125000004494 ethyl ester group Chemical group 0.000 description 4
- 208000006454 hepatitis Diseases 0.000 description 4
- 238000010253 intravenous injection Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 3
- 206010008909 Chronic Hepatitis Diseases 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 3
- 230000002440 hepatic effect Effects 0.000 description 3
- 229960000890 hydrocortisone Drugs 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 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 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 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
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- SQVRNKJHWKZAKO-PFQGKNLYSA-N N-acetyl-beta-neuraminic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-PFQGKNLYSA-N 0.000 description 2
- GQUWTUCOMVXQQE-RGMNGODLSA-M [Na+].C(CC)N[C@@H](CCO)C(=O)[O-] Chemical compound [Na+].C(CC)N[C@@H](CCO)C(=O)[O-] GQUWTUCOMVXQQE-RGMNGODLSA-M 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- XMXOIHIZTOVVFB-JIZZDEOASA-L disodium;(2s)-2-aminobutanedioate Chemical class [Na+].[Na+].[O-]C(=O)[C@@H](N)CC([O-])=O XMXOIHIZTOVVFB-JIZZDEOASA-L 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 108010074605 gamma-Globulins Proteins 0.000 description 2
- 206010019692 hepatic necrosis Diseases 0.000 description 2
- 230000007866 hepatic necrosis Effects 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 231100000820 toxicity test Toxicity 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- MEIRRNXMZYDVDW-MQQKCMAXSA-N (2E,4E)-2,4-hexadien-1-ol Chemical compound C\C=C\C=C\CO MEIRRNXMZYDVDW-MQQKCMAXSA-N 0.000 description 1
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 108020004206 Gamma-glutamyltransferase Proteins 0.000 description 1
- 240000008917 Glycyrrhiza uralensis Species 0.000 description 1
- 235000000554 Glycyrrhiza uralensis Nutrition 0.000 description 1
- 206010019668 Hepatic fibrosis Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 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
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 1
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 231100000762 chronic effect Toxicity 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000011082 depyrogenation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002213 flavones Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 102000006640 gamma-Glutamyltransferase Human genes 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 235000021374 legumes Nutrition 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229910000150 monocalcium phosphate Inorganic materials 0.000 description 1
- 235000019691 monocalcium phosphate Nutrition 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 150000008130 triterpenoid saponins Chemical class 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
实验组 | 剂量mg/kg | 动物数(只) | 血清转氨酶 | 肝组织 | |
AlaAT(IU/L) | AspAT(IU/L) | 肝细胞坏死数 | |||
正常对照 | 生理盐水 | 10 | 90±10 | 285±30 | 0 |
中毒对照 | 生理盐水 | 10 | 6900±850 | 8000±1357 | 84±40 |
化合物ANa | 25 | 10 | 4120±1004B | 5543±1874B | 60±20B |
化合物ANa | 50 | 10 | 3075±1267A,C | 3350±1387A,C | 43±12A,C |
化合物ANa | 100 | 10 | 2001±1000A, | 2650±1256A | 38±10A,C |
甘草酸单氨盐 | 50 | 10 | 4500±1020A | 5250±1435A | 70±15B |
实验组 | 剂量mg/kg | 动物数(只) | 血清转氨酶 | 血清蛋白 | |
AlaAT(IU/L) | AspAT(IU/L) | 白蛋白(g/L) | |||
正常对照 | 生理盐水 | 10 | 90±15 | 295±30 | 45±4.3 |
中毒对照 | 生理盐水 | 10 | 5000±1820 | 8600±2134 | 28±2.0 |
化合物ANa | 15 | 10 | 3120±1504A | 6143±1987B | 33±1.0A |
化合物ANa | 30 | 10 | 2810±1367A | 4398±1887A | 36±1.2A |
化合物ANa | 60 | 10 | 1500±735A,C | 3650±1568B,C | 40±2.3A |
甘草酸单铵盐 | 60 | 10 | 2840±1311A | 5213±1825B | 32±1.5A |
实验组 | 剂量 | 动物数 | 血清 | 肝组织 |
mg/kg | (只) | NANA(μmol/L) | HA(ng/ml) | Hyp(μmol/g) | S(平均期数) | |
正常对照 | 生理盐水 | 10 | 14.80±3.2 | 701±154 | 1.95±0.85 | 0 |
中毒对照 | 生理盐水 | 10 | 59.90±6.2 | 1478±68 | 11.55±2.05 | 4.0 |
化合物ANa | 15 | 10 | 46.50±7.2A | 1372±136A | 6.35±1.85A | 3.4A |
化合物ANa | 30 | 10 | 40.48±5.9A | 1158±268A | 5.13±1.93B | 3.0A |
化合物ANa | 60 | 10 | 32.67±2.2B,C | 1034±235A,C | 3.25±1.05B,C | 2.8A,C |
甘草酸单铵盐 | 60 | 10 | 43.85±4.2B | 1344±125A | 4.83±1.72B | 3.6A |
实验组 | 剂量mg/kg | 动物数(只) | 血清转氨酶 | 血清蛋白 | ||
AlaAT(IU/L) | AspAT(IU/L) | 白蛋白(g/dl) | γ-球蛋白 | |||
正常对照 | 生理盐水 | 10 | 61.3±13 | 110.2±13 | 4.13±1.0 | 0.38±0.04 |
中毒对照 | 生理盐水 | 10 | 122.3±45 | 248.2±89 | 2.73±0.9 | 0.78±0.14 |
化合物ANa | 50 | 10 | 86.7±18A | 150.2±53B | 3.83±1.0A | 0.58±0.12A |
化合物ANa | 100 | 10 | 76.3±15A | 150.4±50A | 4.02±1.0A | 0.48±0.10B |
化合物ANa | 150 | 10 | 71.3±23A | 124.2±33B | 3.88±0.8A | 0.39±0.12 |
甘草酸单铵盐 | 100 | 10 | 80.3.3±19B | 150.2±58A | 3.99±1.0A | 0.55±0.11A |
实验组 | 剂量没g/kg | 动物数(只) | 血浆NO(mol/L)X±s | 脾重(mg)X±s | 死亡率(%) |
正常对照 | 生理盐水 | 10 | 12.5±3 | 78±10 | 0 |
中毒对照 | 生理盐水 | 10 | 36.0±11 | 179±23 | 66.7 |
化合物ANa | 50 | 10 | 23.3±3B | 130±20B | 40.0A |
化合物ANa | 100 | 10 | 20.0±4A,C | 110±18A | 20.0B,C |
化合物ANa | 150 | 10 | 18.2±3A | 90±20A | 10.0B |
甘草酸单铵盐 | 100 | 10 | 23.8±5A | 124±17A | 33.3B |
药物 | 动物 | 给药途径 | LD50(mg/kg) |
化合物ANa | ICR小鼠 | 静脉注射 | 1020 |
甘草酸单铵盐 | ICR小鼠 | 静脉注射 | 580 |
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200610127322 CN1911954A (zh) | 2006-09-14 | 2006-09-14 | 带氨基酸的甘草酸衍生物、其制备方法及含有它们的药物组合物 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200610127322 CN1911954A (zh) | 2006-09-14 | 2006-09-14 | 带氨基酸的甘草酸衍生物、其制备方法及含有它们的药物组合物 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1911954A true CN1911954A (zh) | 2007-02-14 |
Family
ID=37721032
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 200610127322 Pending CN1911954A (zh) | 2006-09-14 | 2006-09-14 | 带氨基酸的甘草酸衍生物、其制备方法及含有它们的药物组合物 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN1911954A (zh) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102716463A (zh) * | 2012-06-19 | 2012-10-10 | 北京中海康医药科技发展有限公司 | 甘草酸有机盐磷脂配位体及其制剂 |
CN103242392A (zh) * | 2012-02-13 | 2013-08-14 | 南京华狮化工有限公司 | 一种新的甘草酸复盐及其制备与应用 |
CN103751777A (zh) * | 2014-01-27 | 2014-04-30 | 中国医学科学院医学生物学研究所 | 甘草酸二铵佐剂及含甘草酸二铵佐剂的疫苗 |
CN108929358A (zh) * | 2017-05-26 | 2018-12-04 | 北京医院 | 精氨酸甘草甜素及其制备方法和用途 |
TWI741769B (zh) * | 2020-08-28 | 2021-10-01 | 中國醫藥大學 | 甘草酸衍生物、其醫藥組合物及其用途 |
WO2022041126A1 (zh) * | 2020-08-28 | 2022-03-03 | 林振文 | 甘草酸衍生物、其医药组合物及其用途 |
CN115677813A (zh) * | 2021-03-25 | 2023-02-03 | 河北中医学院 | 化合物在tmem16a激动剂中的应用 |
-
2006
- 2006-09-14 CN CN 200610127322 patent/CN1911954A/zh active Pending
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103242392A (zh) * | 2012-02-13 | 2013-08-14 | 南京华狮化工有限公司 | 一种新的甘草酸复盐及其制备与应用 |
CN103242392B (zh) * | 2012-02-13 | 2016-04-13 | 南京华狮化工有限公司 | 一种甘草酸复盐及其制备与应用 |
CN102716463A (zh) * | 2012-06-19 | 2012-10-10 | 北京中海康医药科技发展有限公司 | 甘草酸有机盐磷脂配位体及其制剂 |
CN103751777A (zh) * | 2014-01-27 | 2014-04-30 | 中国医学科学院医学生物学研究所 | 甘草酸二铵佐剂及含甘草酸二铵佐剂的疫苗 |
CN103751777B (zh) * | 2014-01-27 | 2016-03-02 | 中国医学科学院医学生物学研究所 | 甘草酸二铵佐剂及含甘草酸二铵佐剂的疫苗 |
CN108929358A (zh) * | 2017-05-26 | 2018-12-04 | 北京医院 | 精氨酸甘草甜素及其制备方法和用途 |
TWI741769B (zh) * | 2020-08-28 | 2021-10-01 | 中國醫藥大學 | 甘草酸衍生物、其醫藥組合物及其用途 |
WO2022041126A1 (zh) * | 2020-08-28 | 2022-03-03 | 林振文 | 甘草酸衍生物、其医药组合物及其用途 |
CN115677813A (zh) * | 2021-03-25 | 2023-02-03 | 河北中医学院 | 化合物在tmem16a激动剂中的应用 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1147472C (zh) | 具有组蛋白脱乙酰酶抑制剂活性的苯甲酰胺制剂 | |
CN1911954A (zh) | 带氨基酸的甘草酸衍生物、其制备方法及含有它们的药物组合物 | |
EP2589382A1 (en) | Pharmaceutical composition comprising levocarnitine and dobesilate | |
CN112979743A (zh) | 白桦脂酸衍生物及其应用 | |
CN1245398C (zh) | 黄芩素的提取工艺、药用组合物及制剂制备工艺 | |
CN1686104A (zh) | 丹参酮固体分散体和包合物及其用途 | |
JP2001064177A (ja) | ベンズアミド誘導体を有効成分とする製剤 | |
CN1820748A (zh) | 一种左旋奥硝唑冻干粉针注射剂 | |
CN1022023C (zh) | 含哌啶子基链烷醇衍生物的液体药物组合物的制备方法 | |
CN1279897C (zh) | 含有双氯芬酸盐和利多卡因的冻干制剂及其制备方法 | |
CN1384090A (zh) | 丹参总酚酸的提取方法及其制剂的制法与用途 | |
WO2014154122A1 (zh) | 双环醇氨基酸酯及其制备方法与应用 | |
CN1556101A (zh) | 汉黄芩素的提取工艺、药用组合物及制剂制备工艺 | |
CN1686151A (zh) | 复方甘草酸及其盐的肠溶制剂及其制备方法 | |
CN100384426C (zh) | 一种含活性成分阿德福韦或其盐的固体分散物及其制备方法 | |
CN1439376A (zh) | 一种抗肺肝纤维化的积雪草苷中药制剂 | |
CN1626085A (zh) | 左西孟旦冻干制剂及其制备方法 | |
CN103284985A (zh) | 稳定的(S)-α-甲基-4-(2-甲基丙基)苯乙酸药物组合物 | |
JP2007023001A (ja) | チアミン類の安定化方法 | |
CN108310371B (zh) | 一种降血脂药物组合物及其用途 | |
CN1995059A (zh) | 带氨基酸的18α-甘草酸衍生物、制备方法及其应用 | |
CN1903869A (zh) | 替比夫定的衍生物盐及其制备方法和药物应用 | |
CN1212114C (zh) | 口服灯盏花素缓释制剂 | |
CN1857289A (zh) | 一种复方甘草酸及其盐的分散片剂及其制备方法 | |
CN1224390C (zh) | 含吡咯并喹啉醌的治疗和预防脂肪肝的药物组合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
ASS | Succession or assignment of patent right |
Owner name: SHEN BINBIN Free format text: FORMER OWNER: HANGZHOU YAOHENG MEDICINE SCIENCE CO., LTD. Effective date: 20080229 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20080229 Address after: Room 202, room 6, rose garden, Yue Yue District, Zhejiang City, Shaoxing Province, China: 312000 Applicant after: Shen Binbin Address before: Building 6, building 18, 1 Miao Miao Road, Zhejiang, Hangzhou, China: 310012.: Applicant before: Hangzhou Yaoheng Medicine Technology Ltd. |
|
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20070214 |