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 thereofInfo
- 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
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/2242—Atrial natriuretic factor complex: Atriopeptins, atrial natriuretic protein [ANP]; Cardionatrin, Cardiodilatin
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Molecular Biology (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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.
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)
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.
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 |
| 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 |
| EP94915078A EP0756491A1 (en) | 1994-04-20 | 1994-04-20 | Use of brain natriuretic peptides (bnp), phosphorylated urodilatine, phosphorylated cdd/anp and combinations thereof |
| 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 |
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)
| 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)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6028055A (en) * | 1996-10-22 | 2000-02-22 | Genetech, Inc. | Receptor selective BNP |
| PL377813A1 (en) | 2002-11-26 | 2006-02-20 | Biocon Limited | 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 |
| WO2006005140A2 (en) | 2004-07-15 | 2006-01-19 | The University Of Queensland | Proteinaceous compounds and uses therefor |
| RU2010114017A (en) * | 2007-09-11 | 2011-10-20 | Мондобайотек Лабораториз Аг (Li) | THERAPEUTIC APPLICATION OF B-TYPE SODIURETIC PEPTIDE AND HUMAN GROWTH HORMONE 1-43 |
Family Cites Families (3)
| 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 |
-
1994
- 1994-04-20 CA CA002188143A patent/CA2188143A1/en not_active Abandoned
- 1994-04-20 WO PCT/EP1994/001237 patent/WO1995028952A1/en not_active Application Discontinuation
Cited By (1)
| 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 |