DE2416302B2 - Dimeres sowie trimeres silybin und deren n-methylglucaminsalz und verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel - Google Patents
Dimeres sowie trimeres silybin und deren n-methylglucaminsalz und verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittelInfo
- Publication number
- DE2416302B2 DE2416302B2 DE19742416302 DE2416302A DE2416302B2 DE 2416302 B2 DE2416302 B2 DE 2416302B2 DE 19742416302 DE19742416302 DE 19742416302 DE 2416302 A DE2416302 A DE 2416302A DE 2416302 B2 DE2416302 B2 DE 2416302B2
- Authority
- DE
- Germany
- Prior art keywords
- silybin
- methylglucamine
- methylglucamine salt
- pvp
- nacl
- 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
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 title claims description 46
- 150000001875 compounds Chemical class 0.000 title claims description 12
- 238000000034 method Methods 0.000 title claims description 8
- 238000004519 manufacturing process Methods 0.000 title description 4
- 229940126601 medicinal product Drugs 0.000 title 1
- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 claims description 77
- SEBFKMXJBCUCAI-UHFFFAOYSA-N NSC 227190 Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-UHFFFAOYSA-N 0.000 claims description 69
- FDQAOULAVFHKBX-UHFFFAOYSA-N Isosilybin A Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC(=CC=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 FDQAOULAVFHKBX-UHFFFAOYSA-N 0.000 claims description 67
- VLGROHBNWZUINI-UHFFFAOYSA-N Silybin Natural products COc1cc(ccc1O)C2OC3C=C(C=CC3OC2CO)C4Oc5cc(O)cc(O)c5C(=O)C4O VLGROHBNWZUINI-UHFFFAOYSA-N 0.000 claims description 67
- 229940043175 silybin Drugs 0.000 claims description 67
- 235000014899 silybin Nutrition 0.000 claims description 67
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 238000001226 reprecipitation Methods 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 49
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 30
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 30
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 30
- 239000011780 sodium chloride Substances 0.000 description 23
- 239000013638 trimer Substances 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
- KPKZJLCSROULON-QKGLWVMZSA-N Phalloidin Chemical compound N1C(=O)[C@@H]([C@@H](O)C)NC(=O)[C@H](C)NC(=O)[C@H](C[C@@](C)(O)CO)NC(=O)[C@H](C2)NC(=O)[C@H](C)NC(=O)[C@@H]3C[C@H](O)CN3C(=O)[C@@H]1CSC1=C2C2=CC=CC=C2N1 KPKZJLCSROULON-QKGLWVMZSA-N 0.000 description 17
- GEVRRJXIMHSJOD-BQRLKCCHSA-N (2r,3r)-3,5,7-trihydroxy-2-[(2r)-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2,3-dihydrochromen-4-one Chemical compound C1=C(O)C(OC)=CC(C2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1.C1=C(O)C(OC)=CC(C2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 GEVRRJXIMHSJOD-BQRLKCCHSA-N 0.000 description 15
- 239000000126 substance Substances 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000003826 tablet Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 108010009711 Phalloidine Proteins 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 239000002253 acid Substances 0.000 description 6
- 239000000178 monomer Substances 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000006116 polymerization reaction Methods 0.000 description 4
- 238000002211 ultraviolet spectrum Methods 0.000 description 4
- 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 3
- 238000004140 cleaning Methods 0.000 description 3
- YIDLJQVKFQDISS-DSGKQNAUSA-L disodium;4-[[(2r,3r)-6-[(2r,3r)-3-(3-carboxylatopropanoyloxy)-5,7-dihydroxy-4-oxo-2,3-dihydrochromen-2-yl]-3-(4-hydroxy-3-methoxyphenyl)-2,3-dihydro-1,4-benzodioxin-2-yl]methoxy]-4-oxobutanoate Chemical compound [Na+].[Na+].C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)OC(=O)CCC([O-])=O)COC(=O)CCC([O-])=O)=C1 YIDLJQVKFQDISS-DSGKQNAUSA-L 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 208000019423 liver disease Diseases 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- -1 4-hydroxy-3-methoxyphenyl Chemical group 0.000 description 2
- 235000019890 Amylum Nutrition 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
- 206010067125 Liver injury Diseases 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000002485 combustion reaction Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 231100000572 poisoning Toxicity 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229960004245 silymarin Drugs 0.000 description 2
- 235000017700 silymarin Nutrition 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- VXVPXMOMXZYJBW-LJTMIZJLSA-N (2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol;sulfuric acid Chemical compound OS(O)(=O)=O.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO VXVPXMOMXZYJBW-LJTMIZJLSA-N 0.000 description 1
- HORQAOAYAYGIBM-UHFFFAOYSA-N 2,4-dinitrophenylhydrazine Chemical compound NNC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O HORQAOAYAYGIBM-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 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
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001929 anti-hepatotoxic effect Effects 0.000 description 1
- 150000001765 catechin Chemical class 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 239000008370 chocolate flavor Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 239000007862 dimeric product Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940116364 hard fat Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000007967 peppermint flavor Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000008030 superplasticizer Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229920001864 tannin Polymers 0.000 description 1
- 239000001648 tannin Substances 0.000 description 1
- 235000018553 tannin Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Priority Applications (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19742416302 DE2416302B2 (de) | 1974-04-04 | 1974-04-04 | Dimeres sowie trimeres silybin und deren n-methylglucaminsalz und verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel |
| FI750735A FI62536C (fi) | 1974-04-04 | 1975-03-14 | Foerfarande foer framstaellning av foer leverns skoetsel laemplig silybinpolymer |
| AT202075A AT340418B (de) | 1974-04-04 | 1975-03-17 | Verfahren zur herstellung von neuen polymeren des silybins und von deren salzen |
| IT21814/75A IT1060377B (it) | 1974-04-04 | 1975-03-28 | Prodotti polimeri della silibina |
| ES436132A ES436132A1 (es) | 1974-04-04 | 1975-03-29 | Procedimiento para la preparacion de compuestos polimericos de la silibina. |
| AR258172A AR203502A1 (es) | 1974-04-04 | 1975-03-31 | Procedimiento para preparar productos de condensacion o polimeros de sibilina(silimarina 1)y sus sales |
| CH417475A CH611293A5 (enExample) | 1974-04-04 | 1975-04-02 | |
| GB13671/75A GB1501429A (en) | 1974-04-04 | 1975-04-03 | Polymers of silymarin i methods for their preparation and compositions containing them |
| CA223,759A CA1047509A (en) | 1974-04-04 | 1975-04-03 | Polymers of silybin |
| FR7510475A FR2266513B1 (enExample) | 1974-04-04 | 1975-04-03 | |
| JP4076975A JPS5314074B2 (enExample) | 1974-04-04 | 1975-04-03 | |
| NL7503960.A NL159103B (nl) | 1974-04-04 | 1975-04-03 | Werkwijze voor de bereiding van een geneesmiddel voor leverziekten, van dit geneesmiddel gevormde produkten en werkwijze voor de bereiding van een farmacologisch werkzame verbinding voor toepassing in de werkwijze voor de bereiding van het geneesmiddel. |
| BE155046A BE827512A (fr) | 1974-04-04 | 1975-04-03 | Nouveaux polymeres de la silybine |
| US05/565,175 US3997671A (en) | 1974-04-04 | 1975-04-04 | Silybin polymers and therapeutic compositions |
| ZA00752134A ZA752134B (en) | 1974-04-04 | 1975-04-04 | New polymers |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19742416302 DE2416302B2 (de) | 1974-04-04 | 1974-04-04 | Dimeres sowie trimeres silybin und deren n-methylglucaminsalz und verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2416302A1 DE2416302A1 (de) | 1976-01-22 |
| DE2416302B2 true DE2416302B2 (de) | 1978-02-02 |
| DE2416302C3 DE2416302C3 (enExample) | 1978-10-05 |
Family
ID=5912093
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19742416302 Granted DE2416302B2 (de) | 1974-04-04 | 1974-04-04 | Dimeres sowie trimeres silybin und deren n-methylglucaminsalz und verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US3997671A (enExample) |
| JP (1) | JPS5314074B2 (enExample) |
| AR (1) | AR203502A1 (enExample) |
| AT (1) | AT340418B (enExample) |
| BE (1) | BE827512A (enExample) |
| CA (1) | CA1047509A (enExample) |
| CH (1) | CH611293A5 (enExample) |
| DE (1) | DE2416302B2 (enExample) |
| ES (1) | ES436132A1 (enExample) |
| FI (1) | FI62536C (enExample) |
| FR (1) | FR2266513B1 (enExample) |
| GB (1) | GB1501429A (enExample) |
| IT (1) | IT1060377B (enExample) |
| NL (1) | NL159103B (enExample) |
| ZA (1) | ZA752134B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2719581A1 (de) * | 1976-05-05 | 1977-11-24 | Inverni Della Beffa Spa | Polyhydroxyphenylchromanone enthaltende arzneimittel |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3537656A1 (de) * | 1984-11-22 | 1986-05-22 | Dr. Madaus GmbH & Co, 5000 Köln | Verfahren zur herstellung von isosilybinfreiem silibinin und arzneimittel, enthaltend silibinin |
| US6913769B2 (en) * | 2003-02-18 | 2005-07-05 | Brian Douglas Oslick | Compositions for prevention and treatment of symptoms associated with ethyl alcohol consumption |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1963318A1 (de) * | 1969-12-17 | 1971-06-24 | Schwabe Willmar Gmbh & Co | Silybinhalbester der Bernsteinsaeure und der Phthalsaeure,ihre Salze mit pharmakologisch vertraglichen Basen,Verfahren zu ihrer Herstellung und ihre Verwendung zur Herstellung von Arzneipraeparaten |
-
1974
- 1974-04-04 DE DE19742416302 patent/DE2416302B2/de active Granted
-
1975
- 1975-03-14 FI FI750735A patent/FI62536C/fi not_active IP Right Cessation
- 1975-03-17 AT AT202075A patent/AT340418B/de not_active IP Right Cessation
- 1975-03-28 IT IT21814/75A patent/IT1060377B/it active
- 1975-03-29 ES ES436132A patent/ES436132A1/es not_active Expired
- 1975-03-31 AR AR258172A patent/AR203502A1/es active
- 1975-04-02 CH CH417475A patent/CH611293A5/xx not_active IP Right Cessation
- 1975-04-03 FR FR7510475A patent/FR2266513B1/fr not_active Expired
- 1975-04-03 BE BE155046A patent/BE827512A/xx unknown
- 1975-04-03 JP JP4076975A patent/JPS5314074B2/ja not_active Expired
- 1975-04-03 GB GB13671/75A patent/GB1501429A/en not_active Expired
- 1975-04-03 NL NL7503960.A patent/NL159103B/xx not_active IP Right Cessation
- 1975-04-03 CA CA223,759A patent/CA1047509A/en not_active Expired
- 1975-04-04 US US05/565,175 patent/US3997671A/en not_active Expired - Lifetime
- 1975-04-04 ZA ZA00752134A patent/ZA752134B/xx unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2719581A1 (de) * | 1976-05-05 | 1977-11-24 | Inverni Della Beffa Spa | Polyhydroxyphenylchromanone enthaltende arzneimittel |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5191272A (enExample) | 1976-08-10 |
| US3997671A (en) | 1976-12-14 |
| AR203502A1 (es) | 1975-09-15 |
| FI62536C (fi) | 1983-01-10 |
| DE2416302C3 (enExample) | 1978-10-05 |
| CH611293A5 (enExample) | 1979-05-31 |
| FR2266513A1 (enExample) | 1975-10-31 |
| ES436132A1 (es) | 1977-02-01 |
| FR2266513B1 (enExample) | 1979-08-10 |
| IT1060377B (it) | 1982-07-10 |
| JPS5314074B2 (enExample) | 1978-05-15 |
| AT340418B (de) | 1977-12-12 |
| NL7503960A (nl) | 1975-10-07 |
| ATA202075A (de) | 1977-04-15 |
| CA1047509A (en) | 1979-01-30 |
| NL159103B (nl) | 1979-01-15 |
| FI62536B (fi) | 1982-09-30 |
| BE827512A (fr) | 1975-10-03 |
| GB1501429A (en) | 1978-02-15 |
| FI750735A7 (enExample) | 1975-10-05 |
| ZA752134B (en) | 1976-04-28 |
| DE2416302A1 (de) | 1976-01-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C3 | Grant after two publication steps (3rd publication) | ||
| 8330 | Complete renunciation |