CH681060A5 - - Google Patents
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- CH681060A5 CH681060A5 CH2728/90A CH272890A CH681060A5 CH 681060 A5 CH681060 A5 CH 681060A5 CH 2728/90 A CH2728/90 A CH 2728/90A CH 272890 A CH272890 A CH 272890A CH 681060 A5 CH681060 A5 CH 681060A5
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- CH
- Switzerland
- Prior art keywords
- sep
- sobrerol
- trans
- head col
- title
- Prior art date
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- 239000004480 active ingredient Substances 0.000 claims abstract description 3
- 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 claims description 17
- 230000000510 mucolytic effect Effects 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 230000000954 anitussive effect Effects 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000000144 pharmacologic effect Effects 0.000 abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- OVKDFILSBMEKLT-UHFFFAOYSA-N alpha-Terpineol Natural products CC(=C)C1(O)CCC(C)=CC1 OVKDFILSBMEKLT-UHFFFAOYSA-N 0.000 abstract 1
- 238000000034 method Methods 0.000 description 6
- 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 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 235000007173 Abies balsamea Nutrition 0.000 description 2
- 239000004857 Balsam Substances 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 244000018716 Impatiens biflora Species 0.000 description 2
- 241001465754 Metazoa Species 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
- 230000001147 anti-toxic effect Effects 0.000 description 2
- 239000002775 capsule Substances 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
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 229960000230 sobrerol Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- OMDMTHRBGUBUCO-UHFFFAOYSA-N trans-sobrerol Natural products CC1=CCC(C(C)(C)O)CC1O OMDMTHRBGUBUCO-UHFFFAOYSA-N 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 1
- 201000004813 Bronchopneumonia Diseases 0.000 description 1
- 208000027775 Bronchopulmonary disease Diseases 0.000 description 1
- 241000252095 Congridae Species 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 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
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000003708 ampul Substances 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
- 206010006451 bronchitis Diseases 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 230000003287 optical effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 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
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000002265 prevention Effects 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
- 230000036280 sedation 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
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet 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
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pulmonology (AREA)
- Zoology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Pharmacological characteristics of 1R-trans-5-hydroxy- alpha , alpha ,4-trimethyl-3-cyclohexene-1-methanol and pharmaceutical compositions containing it as the active ingredient are described.
Description
Gegenstand der Erfindung sind mukolytisch- und zentralantitusisch-aktive pharmazeutische Zusammensetzungen, die als Hauptaktivanteil (-)-trans-Sobrerol (1R-trans-5-hydroxy- alpha , alpha ,4-trimethyl-3-cyklohexen-1-methanol) enthalten.
Sobrerol ist ein bekanntes pharmazeutisches Mukolytikum, das in der Therapie schon lange wegen seiner mukolytischen Wirkung angewendet wird.
Sobrerol, dessen Formel nachstehend angegeben ist, besteht aus zwei asymmetrischen Kohlenstoffatomen und stellt daher ein Gemisch aus zwei diastereoisomeren und enantiomeren Paaren dar, von dem sich ergeben hat, dass bislang seine pharmakologischen Eigenschaften noch nicht untersucht wurden.
EMI1.1
Die chemisch-physikalischen Eigenschaften der Sobrerol-Enantiomere wurden jedoch untersucht (Congr. Int. Technol. Pharm. 1989 Vol. I 232-40, Chem Abstr. 112 (8) 62485).
Man hat nun festgestellt, dass das (-)-trans-Sobrerol des Enantiomers in bezug auf das Razematsobrerol günstige pharmakologische Eigenschaften besitzt, und es sich insbesondere durch eine geringere Toxizität und eine völlig überraschende antitoxische Wirkung auf zentralem Niveau auszeichnet, was bislang beim Razematsobrerol weder beschrieben wurde noch bekannt war.
Die Erfindung gibt somit pharmazeutische Zusammensetzungen an, die als Hauptwirkstoff (-)-trans-Sobrerol enthalten, das für die pathologische Behandlung von akuten und chronischen, bronchopulmonaren Erkrankungen wie Bronchitis, Lungenentzündungen, Bronchopneumonien, Bronchiektroven und ganz allgemein, von allen solchen Fällen in denen eine Sedierung symptomatologischen Hustens und/oder eine Regelung der Schleimausscheidung gewünscht wird, anwendbar ist.
Die Zusammensetzungen gemäss der Erfindung können durch Anwendung bekannter Techniken bzw. Bindetechniken hergestellt werden, wie etwa jener, wie sie beschrieben sind in Remingtons Pharmaceutical Science Handbook, Mack Pub. Co., N.Y., USA, 17a Ed.
Geeignete Verabreichungsformen sind Kapseln, Tabletten, Pulver in Tütchen, Sirupe, parenteral oder in Form von Aerosolen verabreichbare Lösungen, Nasentropfen und dergleichen. Die Einheitsdosis der Hauptwirksubstanz kann zwischen 10 bis 500 mg variieren, wogegen die allgemeine Posologie von mehreren Faktoren abhängt (Pathologie, Zustand des Patienten): bei einem Erwachsenen mit einem Gewicht von 70 kg kann man im allgemeinen 100 bis 1000 mg pro Tag verabreichen, eventuell aufgeteilt auf mehrere Male.
(-)-trans-Sobrerol kann mit bekannten Verfahren hergestellt werden, wie beispielsweise jenen, die in der erstgenannten Veröffentlichung beschrieben wurden, oder mit den konventionellen asymmetrischen Syntheseverfahren, der Isomertrennung und optischen Ausflösung. Ein bekanntes Verfahren sieht die Verwendung von 1- alpha -Pinenoxyd als Ausgangsstoff vor.
Nützliche Hinweise zur Herstellung von (-)-trans-Sobrerol finden sich beispielsweise in Helv. Chim. Acta 1987, 70(1), 71-8.
Nachstehend werden die Ergebnisse pharmakologischer Tests im Vergleich zu Razematsobrerol angegeben.
<tb><TABLE> Columns=4
<tb>Title: Akute Toxizität
<tb>Head Col 01 AL=L: Verbindung
<tb>Head Col 02 AL=L: DL 50 i.p.
bei Mäusen
<tb>Head Col 03 AL=L: DL 50 oral
bei Mäusen
<tb>Head Col 04 AL=L: DL 50 e.v.
bei Mäusen
<tb> <SEP>(-)-trans-Sobrerol <SEP>5000 mg/kg <SEP>5000 mg/kg
<tb> <SEP>Razematsobrerol <SEP>2550 mg/kg <SEP>1100 mg/kg
<tb></TABLE>
<tb><TABLE> Columns=4
<tb>Title: Mukolytische Wirksamkeit
(Mawatarimethode: Mawatari H.
Kagashima Daigaku-Zesshi 27,561; 1976)
<tb>Head Col 01 AL=L: Verbindung
<tb>Head Col 02 AL=L: Anzahl Tiere
<tb>Head Col 03 AL=L: Verabreichte Dosis
mg/kg/os
<tb>Head Col 04 AL=L: % Durchmesser von Fl Na
in bezug auf Kontrollen
<tb> <SEP>(-)-trans-Sobrerol <SEP>10 <SEP>500 <SEP>46,4
<tb> <SEP>Razematsobrerol <SEP>10 <SEP>500 <SEP>33,4
<tb></TABLE>
<tb><TABLE> Columns=5
<tb>Title: Antitoxische Wirksamkeit
<tb>Head Col 01 AL=L: Behandlung
<tb>Head Col 02 AL=L: Anzahl Tiere
<tb>Head Col 03 AL=L: Dosis
mg/kg/ip
<tb>Head Col 04 to 05 AL=L: Huster
<tb>SubHead Col 04 AL=L>Mittel:
<tb>SubHead Col 05 AL=L>% Verhinderung verglichen mit Kontrollen:
<tb> <SEP>Kontrollen <SEP>12 <SEP>- <SEP>12,4 <SEP>-
<tb> <SEP>Rezematsobrerol <SEP>12 <SEP>250 <SEP>9,8 <SEP>20,9
<tb> <SEP>(-)-trans-Sobrerol <SEP>12 <SEP>250 <SEP>3,7 <SEP>70,2
<tb></TABLE>
Studenttest
Die nachfolgenden Beispiele dienen zur Illustration der Erfindung
<tb><TABLE> Columns=5
<tb>Title: 1) Kapseln
<tb>Head Col 03 AL=L: A
<tb>Head Col 04 AL=L: B
<tb>Head Col 05 AL=L: C
<tb> <SEP>(-)-trans-Sobrerol <SEP>mg <SEP>100 <SEP>200 <SEP>300
<tb> <SEP>Laktose <SEP>mg <SEP>12 <SEP>24 <SEP>36
<tb> <SEP>Malzdextrin <SEP>mg <SEP>6 <SEP>16 <SEP>24
<tb> <SEP>Polyvinylpirrolidon <SEP>mg <SEP>7 <SEP>14 <SEP>21
<tb> <SEP>Magnesiumsstearat <SEP>mg <SEP>2 <SEP>4 <SEP>6
<tb></TABLE>
<tb><TABLE> Columns=5
<tb>Title: 2) Suppositorien
<tb> <SEP>(-)-trans-Sobrerol <SEP>mg <SEP>20 <SEP>100 <SEP>200
<tb> <SEP>Glyzeride <SEP>mg <SEP>800 <SEP>1000 <SEP>1600
<tb></TABLE>
<tb><TABLE> Columns=5
<tb>Title:
3) Pulver
<tb> <SEP>(-)-trans-Sobrerol <SEP>mg <SEP>100 <SEP>200 <SEP>300
<tb> <SEP>Aromate <SEP>mg <SEP>110 <SEP>220 <SEP>330
<tb> <SEP>Zitronensäure <SEP>mg <SEP>5 <SEP>10 <SEP>15
<tb> <SEP>Saccharin <SEP>mg <SEP>4 <SEP>8 <SEP>12
<tb> <SEP>Aspartam <SEP>mg <SEP>5 <SEP>10 <SEP>15
<tb> <SEP>Polysorbat 20 <SEP>mg <SEP>1,5 <SEP>3 <SEP>4,5
<tb> <SEP>Sorbitol <SEP>mg <SEP>750 <SEP>1500 <SEP>2250
<tb></TABLE>
<tb><TABLE> Columns=4
<tb>Title: 4) Sirup
<tb>
<tb>Head Col 01 to 04 AL=L: 100 ml Sirup enthalten
<tb> <SEP>(-)-trans-Sobrerol <SEP>mg <SEP>1000 <SEP>2000
<tb> <SEP>Saccharose <SEP>mg <SEP>40 <SEP>40
<tb> <SEP>Methyl-p-Hydroxibenzoat <SEP>mg <SEP>200 <SEP>200
<tb> <SEP>Balsamaroma <SEP>mg <SEP>200 <SEP>200
<tb> <SEP>Reinwasser q.b.
<SEP>ml <SEP>100 <SEP>100
<tb></TABLE>
<tb><TABLE> Columns=4
<tb>Title: 5) Elixier
<tb>Head Col 01 to 04 AL=L: 100 ml Elixier enthalten
<tb> <SEP>(-)-trans-Sobrerol <SEP>mg <SEP>1000 <SEP>2000
<tb> <SEP>Saccharose <SEP>mg <SEP>40 <SEP>40
<tb> <SEP>Äthylalkohol <SEP>mg <SEP>10 000 <SEP>10 000
<tb> <SEP>Balsamextrakt <SEP>mg <SEP>1000 <SEP>1000
<tb> <SEP>Methyl-p-Hydroxibenzoat <SEP>mg <SEP>100 <SEP>100
<tb> <SEP>Reinwasser q.b. <SEP>ml <SEP>100 <SEP>100
<tb></TABLE>
<tb><TABLE> Columns=4
<tb>Title: 6) Ampullen
<tb> <SEP>(-)-trans-Sobrerol <SEP>mg <SEP>30 <SEP>60
<tb> <SEP>Reinwasser q.b. <SEP>ml <SEP>2 <SEP>4
<tb></TABLE>
<tb><TABLE> Columns=4
<tb>Title: 7) Aerosolampulle
<tb> <SEP>(-)-trans-Sobrerol <SEP>mg <SEP>30
<tb> <SEP>Reinwasser q.b. <SEP>ml <SEP>3 <SEP>3
<tb></TABLE>
The invention relates to mucolytically and centrally antitusically active pharmaceutical compositions which contain (-) - trans-sobrerol (1R-trans-5-hydroxy-alpha, alpha, 4-trimethyl-3-cyclohexene-1-methanol) as the main active component.
Sobrerol is a well-known pharmaceutical mucolytic that has been used in therapy for a long time because of its mucolytic effect.
Sobrerol, the formula of which is given below, consists of two asymmetric carbon atoms and is therefore a mixture of two diastereoisomeric and enantiomeric pairs, which has been shown to have so far not been studied for its pharmacological properties.
EMI1.1
However, the chemical-physical properties of the sobrerol enantiomers were examined (Congr. Int. Technol. Pharm. 1989 Vol. I 232-40, Chem Abstr. 112 (8) 62485).
It has now been found that the (-) - trans-sobrerol of the enantiomer has favorable pharmacological properties with respect to the razematsobrerol, and it is characterized in particular by a lower toxicity and a completely surprising antitoxic effect at a central level, which has hitherto neither been the case with the razematsobrerol was described was still known.
The invention thus provides pharmaceutical compositions containing (-) - trans-sobrerol as the main active ingredient, which is suitable for the pathological treatment of acute and chronic bronchopulmonary diseases such as bronchitis, pneumonia, bronchopneumonia, bronchiectroven and in general, of all such cases in which sedation of symptomatological cough and / or regulation of mucus excretion is applicable.
The compositions according to the invention can be made using known techniques or binding techniques, such as those described in Remington's Pharmaceutical Science Handbook, Mack Pub. Co., N.Y., USA, 17a Ed.
Suitable forms of administration are capsules, tablets, powders in sachets, syrups, parenterally or in the form of aerosols administrable solutions, nasal drops and the like. The unit dose of the main active substance can vary between 10 to 500 mg, whereas the general posology depends on several factors (pathology, patient's condition): in an adult weighing 70 kg, it is generally possible to administer 100 to 1000 mg per day, possibly divided into several times.
(-) - Trans-sobrerol can be prepared by known methods, such as those described in the former publication, or by the conventional asymmetric synthesis methods, isomer separation and optical resolution. A known method provides for the use of 1-alpha -pine oxide as the starting material.
Helv. Chim, for example, provides useful information on the production of (-) - trans-sobrerol. Acta 1987, 70 (1), 71-8.
The results of pharmacological tests compared to razematsobrerol are given below.
<tb> <TABLE> Columns = 4
<tb> Title: Acute toxicity
<tb> Head Col 01 AL = L: connection
<tb> Head Col 02 AL = L: DL 50 i.p.
in mice
<tb> Head Col 03 AL = L: DL 50 oral
in mice
<tb> Head Col 04 AL = L: DL 50 e.v.
in mice
<tb> <SEP> (-) - trans-sobrerol <SEP> 5000 mg / kg <SEP> 5000 mg / kg
<tb> <SEP> Razematsobrerol <SEP> 2550 mg / kg <SEP> 1100 mg / kg
<tb> </TABLE>
<tb> <TABLE> Columns = 4
<tb> Title: Mucolytic effectiveness
(Mawatari method: Mawatari H.
Kagashima Daigaku-Zesshi 27.561; 1976)
<tb> Head Col 01 AL = L: connection
<tb> Head Col 02 AL = L: number of animals
<tb> Head Col 03 AL = L: dose administered
mg / kg / os
<tb> Head Col 04 AL = L:% diameter of Fl Na
in terms of controls
<tb> <SEP> (-) - trans-sobrerol <SEP> 10 <SEP> 500 <SEP> 46.4
<tb> <SEP> Razematsobrerol <SEP> 10 <SEP> 500 <SEP> 33.4
<tb> </TABLE>
<tb> <TABLE> Columns = 5
<tb> Title: Antitoxic effectiveness
<tb> Head Col 01 AL = L: treatment
<tb> Head Col 02 AL = L: number of animals
<tb> Head Col 03 AL = L: dose
mg / kg / ip
<tb> Head Col 04 to 05 AL = L: Huster
<tb> SubHead Col 04 AL = L> Medium:
<tb> SubHead Col 05 AL = L>% prevention compared to controls:
<tb> <SEP> controls <SEP> 12 <SEP> - <SEP> 12.4 <SEP> -
<tb> <SEP> Rezematsobrerol <SEP> 12 <SEP> 250 <SEP> 9.8 <SEP> 20.9
<tb> <SEP> (-) - trans-sobrerol <SEP> 12 <SEP> 250 <SEP> 3.7 <SEP> 70.2
<tb> </TABLE>
Student test
The following examples serve to illustrate the invention
<tb> <TABLE> Columns = 5
<tb> Title: 1) capsules
<tb> Head Col 03 AL = L: A
<tb> Head Col 04 AL = L: B
<tb> Head Col 05 AL = L: C
<tb> <SEP> (-) - trans-sobrerol <SEP> mg <SEP> 100 <SEP> 200 <SEP> 300
<tb> <SEP> lactose <SEP> mg <SEP> 12 <SEP> 24 <SEP> 36
<tb> <SEP> malt dextrin <SEP> mg <SEP> 6 <SEP> 16 <SEP> 24
<tb> <SEP> polyvinylpyrrolidone <SEP> mg <SEP> 7 <SEP> 14 <SEP> 21
<tb> <SEP> Magnesium stearate <SEP> mg <SEP> 2 <SEP> 4 <SEP> 6
<tb> </TABLE>
<tb> <TABLE> Columns = 5
<tb> Title: 2) suppositories
<tb> <SEP> (-) - trans-sobrerol <SEP> mg <SEP> 20 <SEP> 100 <SEP> 200
<tb> <SEP> Glyceride <SEP> mg <SEP> 800 <SEP> 1000 <SEP> 1600
<tb> </TABLE>
<tb> <TABLE> Columns = 5
<tb> Title:
3) powder
<tb> <SEP> (-) - trans-sobrerol <SEP> mg <SEP> 100 <SEP> 200 <SEP> 300
<tb> <SEP> Aromate <SEP> mg <SEP> 110 <SEP> 220 <SEP> 330
<tb> <SEP> citric acid <SEP> mg <SEP> 5 <SEP> 10 <SEP> 15
<tb> <SEP> Saccharin <SEP> mg <SEP> 4 <SEP> 8 <SEP> 12
<tb> <SEP> Aspartame <SEP> mg <SEP> 5 <SEP> 10 <SEP> 15
<tb> <SEP> polysorbate 20 <SEP> mg <SEP> 1.5 <SEP> 3 <SEP> 4.5
<tb> <SEP> Sorbitol <SEP> mg <SEP> 750 <SEP> 1500 <SEP> 2250
<tb> </TABLE>
<tb> <TABLE> Columns = 4
<tb> Title: 4) Syrup
<tb>
<tb> Head Col 01 to 04 AL = L: 100 ml syrup included
<tb> <SEP> (-) - trans-sobrerol <SEP> mg <SEP> 1000 <SEP> 2000
<tb> <SEP> sucrose <SEP> mg <SEP> 40 <SEP> 40
<tb> <SEP> Methyl p-hydroxibenzoate <SEP> mg <SEP> 200 <SEP> 200
<tb> <SEP> Balsam Flavor <SEP> mg <SEP> 200 <SEP> 200
<tb> <SEP> pure water q.b.
<SEP> ml <SEP> 100 <SEP> 100
<tb> </TABLE>
<tb> <TABLE> Columns = 4
<tb> Title: 5) Elixir
<tb> Head Col 01 to 04 AL = L: 100 ml elixir included
<tb> <SEP> (-) - trans-sobrerol <SEP> mg <SEP> 1000 <SEP> 2000
<tb> <SEP> sucrose <SEP> mg <SEP> 40 <SEP> 40
<tb> <SEP> ethyl alcohol <SEP> mg <SEP> 10,000 <SEP> 10,000
<tb> <SEP> balsam extract <SEP> mg <SEP> 1000 <SEP> 1000
<tb> <SEP> Methyl p-hydroxibenzoate <SEP> mg <SEP> 100 <SEP> 100
<tb> <SEP> pure water q.b. <SEP> ml <SEP> 100 <SEP> 100
<tb> </TABLE>
<tb> <TABLE> Columns = 4
<tb> Title: 6) Ampoules
<tb> <SEP> (-) - trans-sobrerol <SEP> mg <SEP> 30 <SEP> 60
<tb> <SEP> pure water q.b. <SEP> ml <SEP> 2 <SEP> 4
<tb> </TABLE>
<tb> <TABLE> Columns = 4
<tb> Title: 7) Aerosol ampoule
<tb> <SEP> (-) - trans-sobrerol <SEP> mg <SEP> 30
<tb> <SEP> pure water q.b. <SEP> ml <SEP> 3 <SEP> 3
<tb> </TABLE>
Claims (2)
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH2728/90A CH681060A5 (en) | 1990-08-22 | 1990-08-22 | |
| PCT/EP1991/001530 WO1992003128A1 (en) | 1990-08-22 | 1991-08-12 | Pharmaceutical compositions with mucolytic and antitussive activity containing (-)-trans-sobrerol |
| AU83274/91A AU8327491A (en) | 1990-08-22 | 1991-08-12 | Pharmaceutical compositions with mucolytic and antitussive activity containing (-)-trans-sobrerol |
| EP91914459A EP0496858A1 (en) | 1990-08-22 | 1991-08-12 | Pharmaceutical compositions with mucolytic and antitussive activity containing (-)-trans-sobrerol |
| JP3513874A JPH05502892A (en) | 1990-08-22 | 1991-08-12 | Pharmaceutical composition with mucolytic activity and antitussive activity containing (-)-trans-sobrerol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH2728/90A CH681060A5 (en) | 1990-08-22 | 1990-08-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH681060A5 true CH681060A5 (en) | 1993-01-15 |
Family
ID=4240272
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH2728/90A CH681060A5 (en) | 1990-08-22 | 1990-08-22 |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0496858A1 (en) |
| JP (1) | JPH05502892A (en) |
| AU (1) | AU8327491A (en) |
| CH (1) | CH681060A5 (en) |
| WO (1) | WO1992003128A1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20030047503A (en) * | 2001-12-11 | 2003-06-18 | 진양제약주식회사 | Sobrerol ·acetaminophen combined dry syrup and solution |
| CN102911890B (en) * | 2011-08-05 | 2014-06-04 | 烟台海上传奇生物科技有限公司 | Pseudomonas capable of metabolizing diethylstilbestrol and application thereof |
| KR101810651B1 (en) * | 2015-09-09 | 2017-12-20 | 한국생명공학연구원 | Composition for preventing of treating muscle weakness diseases comprising sobrerol |
| CN111107843B (en) * | 2017-06-30 | 2024-01-09 | 财团法人工业技术研究院 | Use of compounds for preparing medicine for treating autoimmune nerve disease and/or neurodegenerative disease, and liquid and controlled release pharmaceutical preparations thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH568951A5 (en) * | 1970-04-17 | 1975-11-14 | Corvi Camillo Spa | |
| IT1180220B (en) * | 1984-08-08 | 1987-09-23 | Corvi Camillo Spa | MIXTURE OF DIASTEREOISOMER COMPOUNDS, OBTAINED FROM (-) - 5- (1-HYDROXY-1-METHYL ETHYL) -2-METHYL-2-CYCLOESEN-1-ONE, HAVING MUCOSECRETOLYTIC ACTIVITY, PROCEDURE FOR ITS PREPARATION AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN |
| DD262874A1 (en) * | 1987-07-31 | 1988-12-14 | Akad Wissenschaften Ddr | PROCESS FOR MICROBIAL TRANSFORMATION OF ALPHA PINENES TO VERBENOLES |
-
1990
- 1990-08-22 CH CH2728/90A patent/CH681060A5/de not_active IP Right Cessation
-
1991
- 1991-08-12 EP EP91914459A patent/EP0496858A1/en not_active Withdrawn
- 1991-08-12 WO PCT/EP1991/001530 patent/WO1992003128A1/en not_active Application Discontinuation
- 1991-08-12 JP JP3513874A patent/JPH05502892A/en active Pending
- 1991-08-12 AU AU83274/91A patent/AU8327491A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JPH05502892A (en) | 1993-05-20 |
| AU8327491A (en) | 1992-03-17 |
| EP0496858A1 (en) | 1992-08-05 |
| WO1992003128A1 (en) | 1992-03-05 |
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Legal Events
| Date | Code | Title | Description |
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| PL | Patent ceased | ||
| PL | Patent ceased |