Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1994-11-15
1996-11-05
Schain, Howard E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 21, C07K 104, C07K 1400, A61K 3802, A61K 3724
Patent
active
055717896
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to the use of the peptide hormone urodilatin for treating pulmonary and/or bronchial diseases.
The use of the peptide hormone urodilatin as a hypotensive agent is known in the field of pharmaceutics (DE 37 06 731.1; DE 37 17 329.4; PCT/EP88/00144).
Obstructive diseases of the air passages are characterized by spasm of the bronchial muscles, swelling of the bronchial mucosa and enhanced production of bronchial secretion in varying intensities. In particular, they comprise bronchial asthma, chronic-obstructive diseases of the air passages (COLD), as well as cardiac asthma. The administration of .beta..sub.2 -sympathomimetics (e.g. fenoterol, salbutamol, terbutalin) is known as a therapy for obstructive diseases of the air passages. .beta..sub.2 -sympathomimetics lower the tonus of the smooth bronchial muscles, and in addition they inhibit release of mediator substances from the mast cells and enhance the mucocilious clarifying function. However, long term and/or high dosage use of .beta..sub.2 -sympathomimetics may result in a desensibilization of .beta..sub.2 -adrenoceptors and hence in a large reduction of therapeutic effectiveness.
In addition, the bronchodilatory activity of the atrial natriuretic peptide (ANP) with asthma is well known (Hulks et al., Br. Med. J. 299 (1989), 1081-1982).
The object of the present invention is to provide a new therapeutic agent for pulmonary and/or bronchial diseases, in particular obstructive diseases of the air passages, that can be used instead of known therapeutic agents or in combination with these.
The object of the invention is achieved by providing a pharmaceutic composition containing urodilatin as the active substance, and optionally pharmaceutically usual diluents, excipients, fillers or adjuvants for treating pulmonary and/or bronchial diseases.
The pharmaceutic composition is especially useful for treating obstructive diseases of the air passages.
The composition is preferably administered parenterally, especially intravenously (e.g. intravenous injection (as a bolus) or intravenous infusion) or inhalatorily, wherein the preferred dosage is from 5 ng to 1000 .mu.g of urodilatin per kg body weight, from 10 ng to 100 .mu.g urodilatin per kg body weight being especially preferred.
In animal experiments it could be shown that with broncho-constriction caused by inhalation of acetylcholin, parenteral administration of urodilatin leads to an obvious protection which becomes apparent in particular in terms of an improved forced expiration.
Surprisingly, it was discovered then that compared with equimolar doses of atrial natriuretic peptide (ANP) the effect of urodilatin was more than two times greater.
Moreover, intravenous application of urodilatin will increase the glomerular filtration rate, the excretion of water, sodium and chloride without the hypotensive effect observed with a similar dosage of ANP. Thus, especially with subjects having a labile circulation urodilatin provides less side effects. The relaxation of the vascular smooth muscles will result in a hypotensive effect only with higher urodilatin doses.
The lower hypotensive effects of urodilatin should also be an advantage, compared with ANP, in a possible therapy of broncho-constriction. In particular the risk of interactions with other hypotensive drugs in the therapy of bronchial asthma, e.g. theophyllin preparations, appears to be diminished.
The invention will be further illustrated by the following Examples in connection with FIGS. 1 to 12.
FIG. 1 shows the forced expiratory flow-volume curve at the end of acetylcholin provocation; full circles=control animals, n=7; open circles=group B: 40 ng/kg/min .DELTA.11.4 pmol/kg/min of urodilatin, n=6 (average values .+-.SEM).
FIG. 2 shows the forced expiratory flow-volume curve at the end of acetylcholin provocation; full circles=control animals, n=7; open circles=group C: 80 ng/kg/min .DELTA.22.8 pmol/kg/min of urodilatin, n=6 (average values .+-.SEM).
FIG. 3 shows the forced expiratory flow-volume curve at the end of acety
REFERENCES:
Hulks et al, British Medical Journal, vol. 299, 28 Oct. 1989 pp. 1081-1082, "Bronchiodilator Effect of Atrial Natriuretic Peptide in Asthma".
Fl uge Thomas
Forssmann Wolf-Georg
HaemoPep Pharma GmbH
Schain Howard E.
Touzeau P. Lynn
LandOfFree
Use of urodilatin in pulmonary and bronchial diseases does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of urodilatin in pulmonary and bronchial diseases, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of urodilatin in pulmonary and bronchial diseases will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2015225