CA2188143A1 - Use of brain natriuretic peptides (bnp), phosphorylated urodilatine, phosphorylated cdd/anp and combinations thereof - Google Patents

Use of brain natriuretic peptides (bnp), phosphorylated urodilatine, phosphorylated cdd/anp and combinations thereof

Info

Publication number
CA2188143A1
CA2188143A1 CA002188143A CA2188143A CA2188143A1 CA 2188143 A1 CA2188143 A1 CA 2188143A1 CA 002188143 A CA002188143 A CA 002188143A CA 2188143 A CA2188143 A CA 2188143A CA 2188143 A1 CA2188143 A1 CA 2188143A1
Authority
CA
Canada
Prior art keywords
combinations
active ingredients
phosphorylated
composition containing
use according
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.)
Abandoned
Application number
CA002188143A
Other languages
French (fr)
Inventor
Wolf-Georg Forssmann
Klaus-Wolf Von Eickstedt
Thomas Fluge
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Haemopep Pharma GmbH
Original Assignee
Individual
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority to DE4241490A priority Critical patent/DE4241490A1/en
Priority claimed from DE4241490A external-priority patent/DE4241490A1/en
Application filed by Individual filed Critical Individual
Priority to AU66465/94A priority patent/AU6646594A/en
Priority to JP7527293A priority patent/JPH09512024A/en
Priority to PCT/EP1994/001237 priority patent/WO1995028952A1/en
Priority to EP94915078A priority patent/EP0756491A1/en
Priority to CA002188143A priority patent/CA2188143A1/en
Publication of CA2188143A1 publication Critical patent/CA2188143A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22Hormones
    • A61K38/2242Atrial natriuretic factor complex: Atriopeptins, atrial natriuretic protein [ANP]; Cardionatrin, Cardiodilatin

Abstract

Use of a pharmaceutic composition containing brain natriuretic peptide (BNP), phosphorylated urodilatin (P-Uro), phosphorylated ANP (P-CDD/ANP) or combinations thereof as well as optionally pharmaceutically usual diluents, vehicles, fillers or auxiliary agents, for the treatment of pulmonary and bronchial diseases.

Description

2~ 881 43 SMB

Use of Brain Natriuretic Peptide (BNP), Phosphorylated Urodilatin, Phosphorylated CDD/ANP and Combinations Thereof The present invention pertains to the use of the peptide hormones brain natriuretic peptide (BNP), phosphorylated urodilatin, phos-phorylated CDD/ANP, and combinations thereof for the treatment of pulmonary and/or bronchial diseases.

Obstructive respiratory tract diseases are characterized by a spasm of bronchial muscles, a swelling of bronchial mucosa, and an increased bronchial secretion in different intensities. They include, in particular, bronchial asthma, chronic-obstructive lung diseases (COLD), and cardinal asthma. A known therapy of obstructive respiratory tract diseases is administering ~2-sym-pathomimetics (e.g., fenoterol, salbutamol, terbutalen). ~2-Sym-pathomimetics decrease the tone of bronchial smooth muscles and, in addition, inhibit the release of mediators from mast cells and increase the mucociliary scavenging function. However, long-term and/or high-dosage application of ~2-sympathomimetics may result in a desensibilization of ~2-adrenoreceptors and thus in a strong decrease of therapeutic efficacy.

The bronchodilatory effect of urodilatin has been detected both in animal studies (Fluge, Hoymann et al., Naunyn-Schmiedebergs Arch. Pharmacol. 345 Suppl. 2, 24 (1992)) and in human asthma patients (Fluge, Wagner et al., Naun. Schmied. Arch. Pharmacol.
345 Suppl. 2, 23 (1992)).

Further, the bronchodilatory activity of atrial natriuretic peptide (ANP) in asthma has been known (Hulks et al., Br. Med.
J. 299 (1989), 1081-1982).

It has been the object of the present invention to provide a new therapeutic agent for pulmonary and/or bronchial diseases, in particular obstructive respiratory tract diseases, which can be used instead of or in combination with known therapeutic agents, and has a superior degree of bronchodilatory activity to known agents, such as atrial natriuretic peptide and urodilatin.

The object according to the invention is achieved by providing a pharmaceutic composition containing brain natriuretic peptide (BNP), phosphorylated urodilatin, phosphorylated ANP or combi-nations thereof as the active ingredients, as well as optionally pharmaceutically usual diluents, vehicles, fillers or auxiliary agents, for the treatment of pulmonary and/or bronchial diseases.

The pharmaceutic composition is particularly useful for the treatment of obstructive respiratory tract diseases.

The composition is preferably administered parenterally, in particular intravenously (e.g. intravenous injeCtiQnS (as a bolus) or intravenous infusion), or by inhalation, the preferred dosage being from 5 ng to 1000 ~g of brain natriuretic peptide (BNP) per kg of body weight, especially preferred from 10 ng to 100 ~g of brain natriuretic peptide (BNP) per kg of body weight.
Intramuscular, succutaneous or parenteral administrations with protective medication are also appropriate in the above-mentioned dosage.

In animal studies, it could be shown that parenteral administra-tion of brain natriuretic peptide (BNP), phosphorylated uro-dilatin, phosphorylated ANP and combinations thereof in a bronchoconstriction caused by acetylcholin inhalation results in a distinct protection which is demonstrated, in particular, by an improved forced expiration.

Surprisin~ly, it has been established that the activities of brain natriuretic peptide (BNP), phosphorylated urodilatin, phos-phorylated ANP and combinations thereof were clearly superior to that of atrial natriuretic peptide (ANP) and urodilatin in the same dosage range.

The invention is further illustrated by the following example.

Example The bronchodilatory effect of brain natriuretic peptide (BNP) was established in adult albino guinea pigs according to the method of Hutson et al. (Am. Rev. Respir. Dis. 137, 548; 1988) using the improved experimental design of Bent, Eltester, Forsting and Schmitz (Naunyn-Schmiedebergs Arch. Pharmacol. Suppl. 1, 381 (1992)). Awake animals were brought into a body box plethysmo-graph in which the extent of bronchoconstriction was measured by means of the respiratory pressure and the maximum of an inspira-tory flow-volume curve. In addition, the respiratory rate and volume were measured. The animals were exposed to an aerosol of an 0.3~ histamin solution in the breathing air for 30 seconds in order to achieve optimum brochoconstriction. Each animal served as its own control in preliminary experiments in which the extent of histamin challenge was established.

In the awake guinea pigs, brain natriuretic peptide (BNP) at an intraperitoneally injected dose of 320 ng of BNP/kg of body weight achieved a pronounced bronchodilatory effect which had a superior degree of activity to that of urodilatin at the same dosage. With 18 animals, atrial natriuretic peptide showed an even smaller bronchodilatory effect than urodilatin in these experiments. Thus, brain natriuretic peptide had a superior degree of activity to those of the peptides already described as having bronchodilatory activities.

Claims (15)

C L A I M S:
1. Use of a pharmaceutic composition containing brain natri-uretic peptide (BNP), phosphorylated urodilatin (P-Uro), phosphorylated ANP (P-CDD/ANP) or combinations thereof as the active ingredients, as well as optionally pharmaceuti-cally usual diluents, vehicles, fillers or auxiliary agents, for the treatment of pulmonary and/or bronchial diseases.
2. The use according to claim 1 for the treatment of obstruc-tive respiratory tract diseases.
3. The use according to claim 1 or 2, characterized in that said composition is administered parenterally, parenterally with protective medication, intramuscularly, subcutane-ously, as an aerosol, by intravenous infusion or intrave-nous bolus administration, or by inhalation.
4. The use according to any of claims 1 to 3, characterized in that said composition containing any of the active ingredi-ents mentioned in claim 1 or combinations thereof is admin-istered in a dosage of from 5 ng to 1000 µg per kilogramm of body weight.
5. The use according to claim 4, characterized in that said composition containing any of the active ingredients men-tioned in claim 1 or combinations thereof is administered in a dosage of from 10 ng to 100 µg per kilogramm of body weight.
6. Use of a pharmaceutic composition containing any of the active ingredients mentioned in claim 1 or combinations thereof and optionally pharmaceutically usual diluents, vehicles, fillers or auxiliary agents, for the preparation of a medicament for the treatment of pulmonary and/or bronchial diseases.
7. The use according to claim 6 for the preparation of a medicament for the treatment of obstructive respiratory tract diseases.
8. The use according to claim 6 or 7, characterized in that a medicament is prepared which can be administered parenter-ally by intravenous route or by inhalation.
9. The use according to any of claims 6 to 8, characterized in that a unit dose of the medicament is administred which comprises from 5 ng to 1000 µg of an active ingredient as mentioned in claim 1 or any combination of such active ingredients per kilogramm of body weight.
10. The use according to claim 9, characterized in that a unit dose of the medicament is administred which comprises from 10 ng to 100 µg of an active ingredient as mentioned in claim 1 or any combination of such active ingredients per kilogramm of body weight.
11. A method for the treatment of pulmonary and/or bronchial diseases, characterized by administering a pharmaceutic composition containing any of the active ingredients men-tioned in claim 1 or combinations thereof and optionally pharmaceutically usual diluents, vehicles, fillers or auxiliary agents.
12. The method according to claim 11 for the treatment of obstructive respiratory tract diseases.
13. The method according to claim 10 or 11, characterized in that said composition is administered parenterally by intravenous route or by inhalation.
14. The method according to any of claims 10 to 13, character-ized in that said composition containing any of the active ingredients mentioned in claim 1 or combinations thereof is administered in a dosage of from 5 ng to 1000 µg per kilo-gramm of body weight.
15. The method according to any of claims 10 to 14, character-ized in that said composition containing any of the active ingredients mentioned in claim 1 or combinations thereof is administered in a dosage of from 10 ng to 100 µg per kilo-gramm of body weight.
CA002188143A 1992-12-09 1994-04-20 Use of brain natriuretic peptides (bnp), phosphorylated urodilatine, phosphorylated cdd/anp and combinations thereof Abandoned CA2188143A1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
DE4241490A DE4241490A1 (en) 1992-12-09 1992-12-09 Brain natriuretic peptide for treating lung and bronchial diseases - more effective at bronchodilation than urodilatin used at the same doses
AU66465/94A AU6646594A (en) 1992-12-09 1994-04-20 Use of brain natriuretic peptides (bnp), phosphorylated urodilatine, phosphorylated cdd/anp and combinations thereof
JP7527293A JPH09512024A (en) 1994-04-20 1994-04-20 Use of brain natriuretic peptide (BNP), phosphorylated urodilatin, phosphorylated CDD / ANP and combinations thereof
PCT/EP1994/001237 WO1995028952A1 (en) 1992-12-09 1994-04-20 Use of brain natriuretic peptides (bnp), phosphorylated urodilatine, phosphorylated cdd/anp and combinations thereof
EP94915078A EP0756491A1 (en) 1994-04-20 1994-04-20 Use of brain natriuretic peptides (bnp), phosphorylated urodilatine, phosphorylated cdd/anp and combinations thereof
CA002188143A CA2188143A1 (en) 1992-12-09 1994-04-20 Use of brain natriuretic peptides (bnp), phosphorylated urodilatine, phosphorylated cdd/anp and combinations thereof

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE4241490A DE4241490A1 (en) 1992-12-09 1992-12-09 Brain natriuretic peptide for treating lung and bronchial diseases - more effective at bronchodilation than urodilatin used at the same doses
PCT/EP1994/001237 WO1995028952A1 (en) 1992-12-09 1994-04-20 Use of brain natriuretic peptides (bnp), phosphorylated urodilatine, phosphorylated cdd/anp and combinations thereof
CA002188143A CA2188143A1 (en) 1992-12-09 1994-04-20 Use of brain natriuretic peptides (bnp), phosphorylated urodilatine, phosphorylated cdd/anp and combinations thereof

Publications (1)

Publication Number Publication Date
CA2188143A1 true CA2188143A1 (en) 1995-11-02

Family

ID=27170206

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002188143A Abandoned CA2188143A1 (en) 1992-12-09 1994-04-20 Use of brain natriuretic peptides (bnp), phosphorylated urodilatine, phosphorylated cdd/anp and combinations thereof

Country Status (2)

Country Link
CA (1) CA2188143A1 (en)
WO (1) WO1995028952A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7033997B2 (en) 1999-09-03 2006-04-25 Pharis Biotec Gmbh Use of natriuretic peptides as antibiotically active substances for the treatment of bacterial infections

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6028055A (en) * 1996-10-22 2000-02-22 Genetech, Inc. Receptor selective BNP
AU2003297583B2 (en) 2002-11-26 2010-01-14 Biocon, Ltd Modified naturetic compounds, conjugates, and uses thereof
GB2403533A (en) 2003-06-30 2005-01-05 Orion Corp Atrial natriuretic peptide and brain natriuretic peptide and assays and uses thereof
ATE496060T1 (en) 2004-07-15 2011-02-15 Univ Queensland PROTEIN-TYPE COMPOUNDS AND APPLICATIONS THEREOF
WO2009033807A2 (en) * 2007-09-11 2009-03-19 Mondobiotech Laboratories Ag Therapeutic uses of b-type natriuretic peptide and human growth hormone 1-43

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3737917A1 (en) * 1987-11-07 1989-05-18 Bissendorf Peptide Gmbh PHOSPHORYLATED DERIVATIVES OF CARDIODILATIN / ANF PEPTIDES
DE4216133A1 (en) * 1992-05-15 1993-11-18 Bissendorf Peptide Gmbh Use of urodilatin in lung and bronchial diseases
DE4241490A1 (en) * 1992-12-09 1994-06-16 Bissendorf Peptide Gmbh Brain natriuretic peptide for treating lung and bronchial diseases - more effective at bronchodilation than urodilatin used at the same doses

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7033997B2 (en) 1999-09-03 2006-04-25 Pharis Biotec Gmbh Use of natriuretic peptides as antibiotically active substances for the treatment of bacterial infections

Also Published As

Publication number Publication date
WO1995028952A1 (en) 1995-11-02

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Legal Events

Date Code Title Description
EEER Examination request
FZDC Discontinued application reinstated
FZDE Discontinued