CS212741B2 - Method of preparing water-soluble salts of effective substances of silymarine group - Google Patents

Method of preparing water-soluble salts of effective substances of silymarine group Download PDF

Info

Publication number: CS212741B2
Authority: CS; Czechoslovakia
Prior art keywords: silymarin; group; smg1; water; liver
Prior art date: 1973-01-19

Application number

CS74253A

Other languages

Czech (cs)

English (en)

Inventor

Rolf Madaus

Guenter Halbach

Wilfied Trost

Original Assignee

Madaus & Co Dr

Priority date (The priority date 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 date listed.)

1973-01-19

Filing date

1974-01-15

Publication date

1982-03-26

1973-01-19 Priority claimed from DE19732302593 external-priority patent/DE2302593C3/de

1974-01-15 Application filed by Madaus & Co Dr filed Critical Madaus & Co Dr

1982-03-26 Publication of CS212741B2 publication Critical patent/CS212741B2/cs

Links

SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical group 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 title claims description 45
150000003839 salts Chemical class 0.000 title claims description 15
238000000034 method Methods 0.000 title claims description 9
239000000126 substance Substances 0.000 title description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
150000001875 compounds Chemical class 0.000 claims description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
235000010841 Silybum marianum Nutrition 0.000 claims description 13
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
239000002904 solvent Substances 0.000 claims description 11
244000272459 Silybum marianum Species 0.000 claims description 8
JMFRWRFFLBVWSI-NSCUHMNNSA-N coniferol Chemical compound COC1=CC(\C=C\CO)=CC=C1O JMFRWRFFLBVWSI-NSCUHMNNSA-N 0.000 claims description 8
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
239000013543 active substance Substances 0.000 claims description 6
239000003960 organic solvent Substances 0.000 claims description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 5
229940119526 coniferyl alcohol Drugs 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
125000001931 aliphatic group Chemical group 0.000 claims description 2
239000007795 chemical reaction product Substances 0.000 claims description 2
238000004821 distillation Methods 0.000 claims description 2
238000010438 heat treatment Methods 0.000 claims description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
235000017700 silymarin Nutrition 0.000 abstract description 27
206010067125 Liver injury Diseases 0.000 abstract description 12
231100000234 hepatic damage Toxicity 0.000 abstract description 11
230000008818 liver damage Effects 0.000 abstract description 11
125000000217 alkyl group Chemical group 0.000 abstract description 3
125000002768 hydroxyalkyl group Chemical group 0.000 abstract description 3
238000006243 chemical reaction Methods 0.000 abstract description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 abstract 1
239000000825 pharmaceutical preparation Substances 0.000 abstract 1
101000864057 Homo sapiens Serine/threonine-protein kinase SMG1 Proteins 0.000 description 36
102100029938 Serine/threonine-protein kinase SMG1 Human genes 0.000 description 36
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 description 27
229960004245 silymarin Drugs 0.000 description 25
239000000243 solution Substances 0.000 description 19
241001465754 Metazoa Species 0.000 description 15
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239000008298 dragée Substances 0.000 description 9
229920000036 polyvinylpyrrolidone Polymers 0.000 description 9
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XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
FLLFKFMTRYRALL-ARQDHWQXSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxy-n-methylhexanamide Chemical class CNC(=O)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FLLFKFMTRYRALL-ARQDHWQXSA-N 0.000 description 8
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UYXAWHWODHRRMR-UHFFFAOYSA-N hexobarbital Chemical compound O=C1N(C)C(=O)NC(=O)C1(C)C1=CCCCC1 UYXAWHWODHRRMR-UHFFFAOYSA-N 0.000 description 6
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238000012360 testing method Methods 0.000 description 6
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
239000003814 drug Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
YWECOPREQNXXBZ-UHFFFAOYSA-N praseodymium(3+);trinitrate Chemical compound [Pr+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O YWECOPREQNXXBZ-UHFFFAOYSA-N 0.000 description 4
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238000001035 drying Methods 0.000 description 3
230000003834 intracellular effect Effects 0.000 description 3
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210000005229 liver cell Anatomy 0.000 description 3
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BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
208000004930 Fatty Liver Diseases 0.000 description 2
206010019708 Hepatic steatosis Diseases 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
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 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
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
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 2
241000700157 Rattus norvegicus Species 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
VLGROHBNWZUINI-UHFFFAOYSA-N Silybin Natural products COc1cc(ccc1O)C2OC3C=C(C=CC3OC2CO)C4Oc5cc(O)cc(O)c5C(=O)C4O VLGROHBNWZUINI-UHFFFAOYSA-N 0.000 description 2
235000021355 Stearic acid Nutrition 0.000 description 2
108090000340 Transaminases Proteins 0.000 description 2
102000003929 Transaminases Human genes 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
239000000853 adhesive Substances 0.000 description 2
230000001070 adhesive effect Effects 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000004945 emulsification Methods 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
208000010706 fatty liver disease Diseases 0.000 description 2
208000006454 hepatitis Diseases 0.000 description 2
230000001771 impaired effect Effects 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
239000008101 lactose Substances 0.000 description 2
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235000019813 microcrystalline cellulose Nutrition 0.000 description 2
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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
238000003825 pressing Methods 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
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229940043175 silybin Drugs 0.000 description 2
235000014899 silybin Nutrition 0.000 description 2
239000008117 stearic acid Substances 0.000 description 2
231100000240 steatosis hepatitis Toxicity 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
238000005303 weighing Methods 0.000 description 2
229940100445 wheat starch Drugs 0.000 description 2
UPLLQJUZZIYKHI-DFWYDOINSA-N (2s)-2-aminopentanedioic acid;2-oxobutanedioic acid Chemical compound OC(=O)CC(=O)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O UPLLQJUZZIYKHI-DFWYDOINSA-N 0.000 description 1
WCWOEQFAYSXBRK-GASJEMHNSA-N (3r,4s,5s,6r)-2-amino-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound NC1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O WCWOEQFAYSXBRK-GASJEMHNSA-N 0.000 description 1
CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
208000030090 Acute Disease Diseases 0.000 description 1
108010082126 Alanine transaminase Proteins 0.000 description 1
101800002638 Alpha-amanitin Proteins 0.000 description 1
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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
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206010016654 Fibrosis Diseases 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
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241000699670 Mus sp. Species 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
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239000002202 Polyethylene glycol Substances 0.000 description 1
RXGJTYFDKOHJHK-UHFFFAOYSA-N S-deoxo-amaninamide Natural products CCC(C)C1NC(=O)CNC(=O)C2Cc3c(SCC(NC(=O)CNC1=O)C(=O)NC(CC(=O)N)C(=O)N4CC(O)CC4C(=O)NC(C(C)C(O)CO)C(=O)N2)[nH]c5ccccc35 RXGJTYFDKOHJHK-UHFFFAOYSA-N 0.000 description 1
NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
239000001785 acacia senegal l. willd gum Substances 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000007059 acute toxicity Effects 0.000 description 1
231100000403 acute toxicity Toxicity 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
239000004007 alpha amanitin Substances 0.000 description 1
CIORWBWIBBPXCG-SXZCQOKQSA-N alpha-amanitin Chemical compound O=C1N[C@@H](CC(N)=O)C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H]([C@@H](C)[C@@H](O)CO)C(=O)N[C@@H](C2)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@H]1C[S@@](=O)C1=C2C2=CC=C(O)C=C2N1 CIORWBWIBBPXCG-SXZCQOKQSA-N 0.000 description 1
CIORWBWIBBPXCG-UHFFFAOYSA-N alpha-amanitin Natural products O=C1NC(CC(N)=O)C(=O)N2CC(O)CC2C(=O)NC(C(C)C(O)CO)C(=O)NC(C2)C(=O)NCC(=O)NC(C(C)CC)C(=O)NCC(=O)NC1CS(=O)C1=C2C2=CC=C(O)C=C2N1 CIORWBWIBBPXCG-UHFFFAOYSA-N 0.000 description 1
238000010171 animal model Methods 0.000 description 1
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102000036639 antigens Human genes 0.000 description 1
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238000003556 assay Methods 0.000 description 1
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238000010876 biochemical test Methods 0.000 description 1
239000003114 blood coagulation factor Substances 0.000 description 1
238000009835 boiling Methods 0.000 description 1
GHAFORRTMVIXHS-UHFFFAOYSA-L bromosulfophthalein sodium Chemical compound [Na+].[Na+].C1=C(S([O-])(=O)=O)C(O)=CC=C1C1(C=2C=C(C(O)=CC=2)S([O-])(=O)=O)C(C(Br)=C(Br)C(Br)=C2Br)=C2C(=O)O1 GHAFORRTMVIXHS-UHFFFAOYSA-L 0.000 description 1
238000002144 chemical decomposition reaction Methods 0.000 description 1
235000019219 chocolate Nutrition 0.000 description 1
239000008370 chocolate flavor Substances 0.000 description 1
230000007882 cirrhosis Effects 0.000 description 1
208000019425 cirrhosis of liver Diseases 0.000 description 1
238000001816 cooling Methods 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
235000011869 dried fruits Nutrition 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
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238000005886 esterification reaction Methods 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000010685 fatty oil Substances 0.000 description 1
238000009472 formulation Methods 0.000 description 1
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210000005228 liver tissue Anatomy 0.000 description 1
238000011068 loading method Methods 0.000 description 1
239000003921 oil Substances 0.000 description 1
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239000000546 pharmaceutical excipient Substances 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
239000002574 poison Substances 0.000 description 1
231100000614 poison Toxicity 0.000 description 1
229920000728 polyester Polymers 0.000 description 1
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239000004302 potassium sorbate Substances 0.000 description 1
229940069338 potassium sorbate Drugs 0.000 description 1
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239000000843 powder Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
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CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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235000019204 saccharin Nutrition 0.000 description 1
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230000002110 toxicologic effect Effects 0.000 description 1
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Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

CS74253A 1973-01-19 1974-01-15 Method of preparing water-soluble salts of effective substances of silymarine group CS212741B2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19732302593 DE2302593C3 (de)		1973-01-19	Salze des Silymarins-I mit Monoaminopoiyhydroxyalkoholen und Verfahren zu deren Herstellung sowie diese enthaltende Arzneimittel

Publications (1)

Publication Number	Publication Date
CS212741B2 true CS212741B2 (en)	1982-03-26

Family

ID=5869427

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS74253A CS212741B2 (en)	1973-01-19	1974-01-15	Method of preparing water-soluble salts of effective substances of silymarine group

Country Status (17)

Country	Link
US (1)	US3994925A (de)
AR (1)	AR202702A1 (de)
AT (1)	AT332535B (de)
BE (1)	BE809864A (de)
CA (1)	CA1025874A (de)
CH (1)	CH593968A5 (de)
CS (1)	CS212741B2 (de)
DD (1)	DD110658A5 (de)
ES (1)	ES422380A1 (de)
FR (1)	FR2214483B1 (de)
GB (1)	GB1387803A (de)
IT (1)	IT1059507B (de)
NL (1)	NL157307B (de)
PH (1)	PH11572A (de)
SE (1)	SE406199B (de)
YU (1)	YU36947B (de)
ZA (1)	ZA74378B (de)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3466053A (en) *	1966-11-14	1969-09-09	William F Whaley	Combined diving catapult and swimming pool
KR100385366B1 (ko) *	2001-03-05	2003-05-27	부광약품 주식회사	생체이용율을 개선한 실리마린 제제 조성물
CZ2008407A3 (cs) *	2008-06-26	2009-08-26	Agra Group, A. S.	Vodorozpustný prípravek na bázi flavanonol lignanu a zpusob jeho prípravy
CZ2008841A3 (cs) *	2008-12-23	2010-07-28	Agra Group, A.S.	Pivo a nápoje na bázi piva a zpusob úpravy obsahu polyfenolu a kremíku v nich
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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
- 1974-01-09 AT AT13174*#A patent/AT332535B/de not_active IP Right Cessation
- 1974-01-11 GB GB136174A patent/GB1387803A/en not_active Expired
- 1974-01-11 IT IT19315/74A patent/IT1059507B/it active
- 1974-01-14 PH PH15410A patent/PH11572A/en unknown
- 1974-01-15 CS CS74253A patent/CS212741B2/cs unknown
- 1974-01-16 FR FR7401484A patent/FR2214483B1/fr not_active Expired
- 1974-01-16 NL NL7400566,A patent/NL157307B/xx not_active IP Right Cessation
- 1974-01-17 ES ES422380A patent/ES422380A1/es not_active Expired
- 1974-01-17 YU YU0128/74A patent/YU36947B/xx unknown
- 1974-01-17 DD DD176059A patent/DD110658A5/xx unknown
- 1974-01-17 BE BE139915A patent/BE809864A/xx not_active IP Right Cessation
- 1974-01-17 SE SE7400609A patent/SE406199B/xx not_active IP Right Cessation
- 1974-01-17 AR AR251984A patent/AR202702A1/es active
- 1974-01-18 CA CA190,635A patent/CA1025874A/en not_active Expired
- 1974-01-18 CH CH72674A patent/CH593968A5/xx not_active IP Right Cessation
- 1974-01-18 ZA ZA00740378A patent/ZA74378B/xx unknown
- 1974-01-21 US US05/435,367 patent/US3994925A/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
AU6460974A (en)	1975-07-17
PH11572A (en)	1978-03-31
US3994925A (en)	1976-11-30
YU12874A (en)	1982-06-18
SE406199B (sv)	1979-01-29
DE2302593B2 (de)	1976-07-08
AR202702A1 (es)	1975-07-15
CA1025874A (en)	1978-02-07
NL7400566A (de)	1974-07-23
IT1059507B (it)	1982-06-21
GB1387803A (en)	1975-03-19
BE809864A (fr)	1974-05-16
NL157307B (nl)	1978-07-17
DD110658A5 (de)	1975-01-05
DE2302593A1 (de)	1974-09-12
ZA74378B (en)	1975-01-29
AT332535B (de)	1976-10-11
ES422380A1 (es)	1976-04-16
FR2214483A1 (de)	1974-08-19
ATA13174A (de)	1976-01-15
FR2214483B1 (de)	1978-01-06
YU36947B (en)	1984-08-31
CH593968A5 (de)	1977-12-30

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EP0439321B1 (de)	1995-03-15	Thiazolidin-Derivate mit antihypertensiver Aktivität und deren therapeutische Anwendung
US3966962A (en)	1976-06-29	Triacetin solutions of PGE-type compounds
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EP0087864A2 (de)	1983-09-07	Pharmazeutische Zusammensetzung
CS212741B2 (en)	1982-03-26	Method of preparing water-soluble salts of effective substances of silymarine group
EP0534907A1 (de)	1993-03-31	Verwendung von Furanonderivaten zur Vorbeugung oder Behandlung von Autoimmunkrankheiten
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WO1991016046A1 (en)	1991-10-31	Use of acetoacetyl carboxylic acid derivatives for immunosuppression
US3803319A (en)	1974-04-09	Treating hyperlipemia with isatin
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WO1994003193A1 (fr)	1994-02-17	Remede contre des maladies intestinales infectieuses bacteriennes dues a des biotoxines
JPS6222714A (ja)	1987-01-30	脂質代謝促進剤
RU2052459C1 (ru)	1996-01-20	Производное хромона, обладающее гипотензивной и аналептической активностью