Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-04-19
2000-02-22
Lambkin, Deborah C.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C07D22102
Patent
active
060281987
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/CN94/00080 Oct. 22, 1994.
The present invention relates to a pharmaceutical composition for prevention and treatment of motion sickness syndrome, the method of its use in the treatment of motion sickness syndrome and a process of preparation of phencynonate hydrochloride as the active component of this pharmaceutical composition.
The motion sickness syndrome is a special syndrome occurring in man under the circumstances of motion, bump or rotation. Its main manifestations are dizziness, pallor, cold sweat, nausea and vomiting. The motion sickness syndrome is frequently seen in the operators and passengers of spacecrafts, seagoing vessels, automobiles and trains. According to the statistics, on an average, 10-30% of the persons during common sea voyage, 1% of the persons during civil aviation and 50-60% of the persons during space flight have motion sickness syndrome in varying degrees. The pathogenesis of motion sickness syndrome is still being studied further, but at present, the recognized chief pathogenesis is a series of central and peripheral cholinergic hyperfunction resulting from hyperexcitation of vestibular cholinergic system of man stimulated by the motion environment.
For many years, extensive researches have been carried out for prevention and treatment of motion sickness syndrome and some drugs have been developed. These drugs can be divided mainly into two groups, i.e. central anti-cholinergics and antihistamines. The representative drug is scopolamine. Although the drugs of these two groups have certain therapeutic effectiveness at their effective dosages, the side effect somnolence to a certain degree is present. Somnolence is a serious potential threat to the operators of spacecrafts, airplanes, seagoing vessels, vehicles and ships, such as being a hidden danger of accident, and also brings about much inconvenience to the passengers or tourists taking these drugs, such as causing lassitude. It is therefore, still necessary to develope an anti-motion sickness drug with high therapeutic effectiveness and minimal side effects.
The object of the present invention is to find an anti-motion sickness drug having high anti-motion sickness effectiveness and minimal side effects, i.e. enabling the patient to keep clear mind while maintaining the anti-motion sickness effectiveness, and overcoming the most obvious side effect of the available anti-motion sickness drugs-somnolence.
Through extensive and deepgoing researches, the inventor found unexpectedly that the pharmaceutical composition containing phencynonate hydrochloride of .alpha.-configuration [3-methyl-3-azabicyclo (3, 3, 1) nonan-9 .alpha.-yl-2-phenyl-2-cyclopentyl-2-hydroxy-acetate] shown in following formula (I) as the active component had excellent anti-motion sickness effectiveness and obviously lower side effect than all the known anti-motion sickness drugs. The present invention was accomplished on the basis of the above finding. ##STR1##
The Spanish patent No. 549496 reported a process of preparation of mandelic acid (hydroxy phenylacetic acid) derivatives. Although the compounds prepared by this process contained 3-methyl-3-azabicyclo (3, 3, 1) nonan-9-yl-2-cyclopentyl 2-hydroxy phenylacetate, the spatial configuration of azabicyclic ester was not involved and their effectiveness in treatment of motion sickness syndrome was not mentioned. Moreover, Zhang Qi-Kai and associates reported the synthesis and anticholinergic activity of a series of .alpha. and .beta. isomers of 3-methyl-3-azabicyclo (3, 3, 1) nonan-9-yl esters in Acta Pharmaceutica Sinica 1984, 19:748-754, but they did not report the structure of the compound involved in the present invention.
The first object of the present invention relates to the pharmaceutical composition containing phencynonate hydrochloride of .alpha.-configuration in formula I as the active component, which has excellent anti-motion sickness efficacy and obviously lower side effect (such as somnolence) than all known anti-motion sickness drugs.
According to the pres
REFERENCES:
patent: 4713391 (1987-12-01), Chiang et al.
patent: 4783478 (1988-11-01), Wootton et al.
patent: 5034398 (1991-07-01), King
patent: 5053412 (1991-10-01), Fisher et al.
patent: 5073560 (1991-12-01), Wu et al.
patent: 5647835 (1997-07-01), Martineau
Zhang Qi-Kai, Acta Pharmaceutica Sinica, 1984, 19: 748-754.
Zhu et al., 1993, Chinese J. Clin. Pharmacol. 9(2):65-74.
Spanish Patent 549,796 by Alonso and Loxano, Oct. 12, 1995.
Liu Chuanhui
Wang Aiping
Wang Weixian
Wang Xiao-ming
Wen Guangling
Institute of Pharmacology and Toxicology Academy of Military Sci
Lambkin Deborah C.
LandOfFree
Pharmaceutical composition for prevention and treatment of motio does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pharmaceutical composition for prevention and treatment of motio, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical composition for prevention and treatment of motio will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-521768