Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-06-15
2000-02-22
Jones, Dwayne C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514396, A01N 4350
Patent
active
060280948
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to an agent for the prevention and depression of dry coughing caused by angiotensin converting enzyme inhibitors, characterized in comprising a thromboxane synthetase inhibitor or thromboxane receptor antagonist as the active ingredient.
BACKGROUND ART
Angiotensin converting enzyme inhibitors are effective antihypertensive drugs and also have preventive effects on the development into cardiac insufficiency and hypertrophy of the heart in hypertensive disease. Therefore, these drugs have been extensively used in the world as one of the first choice drugs for the treatment of hypertension and are very highly useful medicaments.
However, the angiotensin converting enzyme inhibitors, for example, captopril and enalapril have been reported to cause dry coughing as one of their side effects with an incidence of 15-20% and 10-33%, respectively (Arch. Intern. Med., Vol. 145, p. 1524 (1985); Arch. Intern. Med., Vol. 148, p. 249(1988); American Heart Journal, Vol. 116, p. 1658(1988); N. Z. Med. J., Vol. 100, pp. 161-163 (1987); British Medical Journal, Vol. 294, pp. 1521-1523 (1987); British Medical Journal, Vol. 299, pp. 12-16 (1989)). Thus, the use of these drugs become impossible in many patients from the above reason, and the treatment for hypertension in such patients is not sufficient.
Accordingly, in the use of highly useful angiotensin converting enzyme inhibitors, it has been greatly desired to develop drugs which depress dry coughing as the side-effect, preferably, without attenuation of their antihypertensive effects.
For resolving this problem, many studies to alleviate the dry coughing have been carried out. However, the mechanism of dry coughing induced by angiotensin converting enzyme inhibitors has not been clearly elucidated yet.
Up to date, it has been advocated as one of the mechanism of the dry coughing induction that bradykinin which accumulates in the process of the conversion of angiotensin I into angiotensin II by angiotensin converting enzyme causes the release of tachykinins (substance P, neurokinin A), and then, the tachykinins stimulate the c-fibers whose activation causes coughing (British Medical Journal, Vol. 294, pp. 1521-1523 (1987); British Medical Journal, Vol. 299, pp. 12-16 (1989); J. Appl. Physiol., Vol. 48, pp. 511-517 (1980); Nature, Vol. 264, pp. 451-453 (1976)).
On the other hand, it has been reported that sulindac, indomethacin and sodium cromoglycate (Intal.RTM.) depressed the dry coughing (THE LANCET, p. 872 (1987); Journal of Cardiovascular Pharmacology, Vol. 19, No. 15, pp. 670-673 (1992); THE LANCET, Vol. 345, pp. 13-16 (1995)). It is also known that indomethacin attenuated the antihypertensive effects of angiotensin converting enzyme inhibitors in patients with essential hypertension (Journal of Hypertension, Vol. 5, pp. 121-128 (1987)). Furthermore, the use of conventional antitussive remedy was not effective in dry coughing caused by angiotensin converting enzyme inhibitors.
Although studies to develop drugs effective in depressing dry coughing caused by angiotensin converting enzyme inhibitors are being eagerly promoted, such drugs which can be put to practical use have not been found.
DISCLOSURE OF INVENTION
The present invention relates to an agent for the prevention and depression of dry coughing caused by angiotensin converting enzyme inhibitors, characterized in comprising a thromboxane synthetase inhibitor or thromboxane receptor antagonist as the active ingredient.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 is a graph illustrating the result of influence of enalapril on thromboxane B.sub.2 concentration in guinea-pig broncho-alveolar lavage fluid. The axis of ordinates shows thromboxane B.sub.2 concentration. The axis of abscissas shows kind and dose of administered drugs. The data show means and standard deviation. The number in columns shows the number of animals. The group marked with * shows the significantly different from the CMC-treated group at p<0.05.
BEST MODE FOR CARRYING OUT THE INVENTION
We
REFERENCES:
Umemura, K. et al., Altered prostaglandin metabolism induced by angiotensin converting enzyme inhibitors in broncho-alveolar lavage fluid of ginea pig. Jpn. J. Pharmacology. 1996, vol. 72, No. 1, pp. 17-21.
Puolijoki, H. et al., cough induced by enalapril byt not by captopril. European Respiratory Journal. Mar. 1989 vol. 2, No. 3, pp. 289-291.
Naomi et al., "Role of endogenous Thromboxane A2 on Dry Cough Induced by Angiotensin Converting Enzyme Inhibitor", Abstract to Therapeutic Research, vol. 14, No. 7, 1993.
Naito et al., "Effects of thromboxane synthetase inhibitors on aggregation of rabbit platelets", Abstract to Eur. J. Pharmacol. 91(1), pp. 41-48, 1983.
Nakashima Mitsuyoshi
Umemura Kazuo
Jones Dwayne C.
Kissei Pharmaceutical Co. Ltd.
Ono Pharmaceutical Co. Ltd.
LandOfFree
Agent for prevention and suppression of dry coughing caused by a does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Agent for prevention and suppression of dry coughing caused by a, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Agent for prevention and suppression of dry coughing caused by a will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-520858