EP0496858A1 - Pharmaceutical compositions with mucolytic and antitussive activity containing (-)-trans-sobrerol - Google Patents
Pharmaceutical compositions with mucolytic and antitussive activity containing (-)-trans-sobrerolInfo
- Publication number
- EP0496858A1 EP0496858A1 EP91914459A EP91914459A EP0496858A1 EP 0496858 A1 EP0496858 A1 EP 0496858A1 EP 91914459 A EP91914459 A EP 91914459A EP 91914459 A EP91914459 A EP 91914459A EP 0496858 A1 EP0496858 A1 EP 0496858A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- sobrerol
- trans
- mucolytic
- pharmaceutical compositions
- antitussive activity
- 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.)
- Withdrawn
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 6
- OMDMTHRBGUBUCO-BDAKNGLRSA-N (1s,5r)-5-(2-hydroxypropan-2-yl)-2-methylcyclohex-2-en-1-ol Chemical compound CC1=CC[C@@H](C(C)(C)O)C[C@@H]1O OMDMTHRBGUBUCO-BDAKNGLRSA-N 0.000 title claims description 22
- 230000000510 mucolytic effect Effects 0.000 title claims description 7
- 230000000954 anitussive effect Effects 0.000 title claims description 6
- 239000004480 active ingredient Substances 0.000 claims abstract description 5
- GRWFGVWFFZKLTI-IUCAKERBSA-N (-)-α-pinene Chemical compound CC1=CC[C@@H]2C(C)(C)[C@H]1C2 GRWFGVWFFZKLTI-IUCAKERBSA-N 0.000 claims description 6
- NQFUSWIGRKFAHK-BDNRQGISSA-N alpha-Pinene epoxide Natural products C([C@@H]1O[C@@]11C)[C@@H]2C(C)(C)[C@H]1C2 NQFUSWIGRKFAHK-BDNRQGISSA-N 0.000 claims description 5
- 229930006723 alpha-pinene oxide Natural products 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 241000589540 Pseudomonas fluorescens Species 0.000 claims description 4
- NQFUSWIGRKFAHK-UHFFFAOYSA-N 2,3-epoxypinane Chemical compound CC12OC1CC1C(C)(C)C2C1 NQFUSWIGRKFAHK-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 2
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- OMDMTHRBGUBUCO-IUCAKERBSA-N (1s,5s)-5-(2-hydroxypropan-2-yl)-2-methylcyclohex-2-en-1-ol Chemical compound CC1=CC[C@H](C(C)(C)O)C[C@@H]1O OMDMTHRBGUBUCO-IUCAKERBSA-N 0.000 description 9
- 244000005700 microbiome Species 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229960000230 sobrerol Drugs 0.000 description 4
- OMDMTHRBGUBUCO-UHFFFAOYSA-N trans-sobrerol Natural products CC1=CCC(C(C)(C)O)CC1O OMDMTHRBGUBUCO-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- -1 1R-trans-5-hydroxy-α Chemical compound 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- 239000000443 aerosol Substances 0.000 description 2
- MVNCAPSFBDBCGF-UHFFFAOYSA-N alpha-pinene Natural products CC1=CCC23C1CC2C3(C)C MVNCAPSFBDBCGF-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 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
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- GRWFGVWFFZKLTI-UHFFFAOYSA-N rac-alpha-Pinene Natural products CC1=CCC2C(C)(C)C1C2 GRWFGVWFFZKLTI-UHFFFAOYSA-N 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 201000004813 Bronchopneumonia Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000252095 Congridae Species 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
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 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
- 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 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 229910019145 PO4.2H2O Inorganic materials 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- DHRRIBDTHFBPNG-UHFFFAOYSA-L magnesium dichloride hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[Cl-].[Cl-] DHRRIBDTHFBPNG-UHFFFAOYSA-L 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 239000013081 microcrystal Substances 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 238000007430 reference method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000019204 saccharin Nutrition 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
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 230000000294 tussive effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/02—Preparation of oxygen-containing organic compounds containing a hydroxy group
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/10—Expectorants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
Definitions
- the present invention relates to pharmaceutical compositions having mucolytic and central antitussive activities containing as the active ingredient (-)- trans-sobrerol, namely 1R-trans-5-hydroxy- ⁇ , ⁇ ,4-trimethyl-3-cyclohexene-1-methanol, of formula (I).
- Sobrerol is a well-known drug and it has been used in therapy for a long time because of its mucolytic activity.
- Sobrerol has two asymmetric carbon atoms, therefore it is normally used in the form of a mixture of two diastereoisomer pairs of enantiomers, whose pharmacological properties have never been studied up to now.
- the invention provides pharmaceutical compositions containing (-)trans-sobrerol as the active ingredient, said compositions being useful in the tre- atment of acute and chronic bronchopulmonary patholo-gies, like bronchitis, pneumonia, bronchopneumonia, bronchiectasis and, generally, all those conditions where soothing the tussive symptomatology and/or regu- lating mucus secretion are desirable.
- compositions of the invention can be prepared according to well-known techniques and excipients, like those described in Remington's Pharmaceutical Sciences Handbook, Mack Pub. Co., N.Y., USA 17 th Ed.
- Suitable administration forms are tablets, capsu- les, sachets, syrups, solutions for the parenteral or aerosol administrations, nasal drops and the like.
- the single dose of active ingredient will range from 10 to 500 mg, while general posology will depend on several factors (pathology, patient conditions) : for instance, for an adult weighing about 70 kg a 100 to 1000 mg/day administration can be provided, optionally divided in several administrations.
- (-)-Trans-sobrerol can be prepared by means of known methods like those described in the above mentioned reference, or conventional methods for the asymmetric synthesis, the isomer separation and the optical resolution.
- a suitable method consists in using 1- ⁇ -pinene oxide as starting material.
- (-)-Trans-sobrerol may also be prepared by microbiological conversion of ⁇ -pinene and ⁇ -pinene epoxide, using a strain of Pseudomonas fluorescens, according to the following method:
- the microorganism used for producing (-)-trans-sobrerol is Pseudomonas fluorescens, whose taxonomic properties have been controlled by the National Collection of Industrial Bacteria (NCIMB, Torry Research Station, Aberdeen, UK).
- Pseudomonas fluorescens is being kept in plates with "nutrient" agar at 30°C.
- the cultures are used to inoculate Erlenmeyer flasks (250 ml) containing 50 ml of the culture medium disclosed in Table 1, and glucose (0.5% by volume) as a sole source of carbon.
- the flasks are then incubated in an orbitant mixer at 150 rpm and
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pulmonology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH2728/90 | 1990-08-22 | ||
| CH2728/90A CH681060A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1990-08-22 | 1990-08-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0496858A1 true EP0496858A1 (en) | 1992-08-05 |
Family
ID=4240272
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP91914459A Withdrawn EP0496858A1 (en) | 1990-08-22 | 1991-08-12 | Pharmaceutical compositions with mucolytic and antitussive activity containing (-)-trans-sobrerol |
Country Status (5)
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20030047503A (ko) * | 2001-12-11 | 2003-06-18 | 진양제약주식회사 | 소브레롤·아세트아미노펜 복합 건조시럽제 및 액제 |
| CN102911890B (zh) * | 2011-08-05 | 2014-06-04 | 烟台海上传奇生物科技有限公司 | 可代谢己烯雌酚的假单胞菌及其应用 |
| WO2017043935A1 (ko) * | 2015-09-09 | 2017-03-16 | 한국생명공학연구원 | 소브레롤을 포함하는 근력 약화 관련 질환의 예방 또는 치료용 조성물 |
| WO2019002889A1 (en) * | 2017-06-30 | 2019-01-03 | Industrial Technology Research Institute | METHOD FOR TREATING AUTOIMMUNE NEUROLOGICAL DISEASE AND / OR NEURODEGENERATIVE DISEASE AND PHARMACEUTICAL FORMULAS FOR LIQUID GALENIC FORM AND CONTROLLED RELEASE GALENIC FORM |
| KR102804780B1 (ko) * | 2024-01-17 | 2025-05-15 | 주식회사 뉴롤메드 | 인지기능 장애의 치료용 조성물 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH568951A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1970-04-17 | 1975-11-14 | Corvi Camillo Spa | |
| IT1180220B (it) * | 1984-08-08 | 1987-09-23 | Corvi Camillo Spa | Miscela di composti diastereoisomeri, ottenuti da (-)-5-(1-idrossi-1-metiletil)-2-metil-2-cicloesen-1-one, avente attivita' mucosecretolitica, procedimento per la sua preparazione e composizioni farmaceutiche che la contengono |
| DD262874A1 (de) * | 1987-07-31 | 1988-12-14 | Akad Wissenschaften Ddr | Verfahren zur mikrobiellen transformation von alpha-pinenen zu verbenolen |
-
1990
- 1990-08-22 CH CH2728/90A patent/CH681060A5/de not_active IP Right Cessation
-
1991
- 1991-08-12 JP JP3513874A patent/JPH05502892A/ja active Pending
- 1991-08-12 WO PCT/EP1991/001530 patent/WO1992003128A1/en not_active Application Discontinuation
- 1991-08-12 EP EP91914459A patent/EP0496858A1/en not_active Withdrawn
- 1991-08-12 AU AU83274/91A patent/AU8327491A/en not_active Abandoned
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9203128A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH05502892A (ja) | 1993-05-20 |
| WO1992003128A1 (en) | 1992-03-05 |
| AU8327491A (en) | 1992-03-17 |
| CH681060A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1993-01-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH0764872B2 (ja) | Ｆｒ９０１２２８物質およびその製造法 | |
| CA2127878C (en) | Fo-1289 substance and its production | |
| US6087540A (en) | Terphenyl compounds and medicines containing the same | |
| EP0496858A1 (en) | Pharmaceutical compositions with mucolytic and antitussive activity containing (-)-trans-sobrerol | |
| JPH0136471B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| JP4257026B2 (ja) | トリプレニルフェノール化合物の選択的製造方法及びこれらの化合物の薬剤としての利用 | |
| JPH08239385A (ja) | Ｆｏ−１２８９物質およびその製造法 | |
| Bothner-By et al. | The asymmetric incorporation of isotopic label in the biogenesis of hyoscyamine | |
| US5801143A (en) | Cyclic depsipeptides useful for treatment of hyperlipemia | |
| JP2004210648A (ja) | 新規マクロライド化合物及びその製造方法 | |
| CH640000A5 (de) | Verfahren zur herstellung eines gemisches neuer derivate von 3-alkyl-1,9-dihydroxy- und 1-hydroxy-9-keto-dibenzo(b,d)pyranen. | |
| US4696948A (en) | Indanyl derivatives and process for their preparation | |
| DE3850276T2 (de) | Serotonin-Inhibitoren und sie enthaltende pharmazeutische Zusammensetzungen und mikrobielle Verfahren und Organismen für ihre Herstellung. | |
| US5198463A (en) | Oxytocin antagonists | |
| JPH0959275A (ja) | 新規物質トリプロスタチン、その製造方法、細胞周期阻害剤および抗腫瘍剤 | |
| WO1996005204A1 (en) | Spirolaxine derivatives for treating gastroduodenal diseases | |
| EP0459449B1 (en) | Furano[2,3-F]isoindoles as aldose reductase inhibitors | |
| JP2004521927A (ja) | Ｃｎｓ障害の治療用薬剤の製造におけるチオルチン二酸化物およびその誘導体の使用、ならびにこれらの製造方法 | |
| JPH02258724A (ja) | 新規抗生物質ｒｋ―２８６ｃ、その製造法並びに抗腫瘍剤及び抗炎症剤 | |
| JPH06184133A (ja) | コレステロールエステラーゼ阻害剤 | |
| EP0629184A1 (en) | TETRALIN DERIVATIVES AS HMG-CoA REDUCTASE INHIBITORS | |
| JPH064634B2 (ja) | 新規化合物ｗｆ１３６０類、その製造法およびその用途 | |
| GB1560799A (en) | Substituted diphenyl ethers | |
| JP2001046092A (ja) | 新規生理活性物質ｎｋ３４９４４、その製造法及びその用途 | |
| JPH0873452A (ja) | 新規抗生物質 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU NL SE |
|
| 17P | Request for examination filed |
Effective date: 19920730 |
|
| 17Q | First examination report despatched |
Effective date: 19940214 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
| 18D | Application deemed to be withdrawn |
Effective date: 19941103 |