Compounds, compositions and method of treatments for improving circulatory performance

• US 4,761,417 A
• Filed: 10/18/1985
• Issued: 08/02/1988
• Est. Priority Date: 05/14/1982
• Status: Expired due to Term

• Current Assignee: Andrew Maroko, Richard Maroko, Robert Maroko
• Original Assignee: Peter R. Maroko
• Inventors: Maroko, Peter R.
• Primary Examiner(s): Waddell, Frederick E.
• Application Number:
  US06/788,507
• Time in Patent Office: 1,019 Days
• Field of Search: 514/280, 514/284, 514/26
• US Class Current: 514/284
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin

Abstract

A method of increasing the contractility of the mammalian heart as shown by a positive inotropic affect is disclosed, employing protoberberine alkaloids such as berberrubine or tetrahydropalmitane, alone or in combination with cardiac glycosides such as ouabain, digoxin, digitoxin or delanoside.

Claims

1. A therapeutic method for increasing contractility of the mammalian heart as shown by a positive inotropic effect which comprises administering to a mammal in need thereof in an amount effective to cause a positive inotropic effect, a composition which comprises a biologically acceptable carrier and a compound selected from the group consisting of berberrubine and the pharmaceutically acceptable salts thereof, causing a positive inotropic effect and discontinuing administration.

2. The therapeutic method of claim 1 wherein the compound is administered periodically.

13. The method of claims 1, 2, 3 or 4 wherein the compound is administered in a dosage in the range of about 0.001 to about 50 mg/kg.

14. The method of claims 1, 2, 3 or 4 wherein the compound is administered in a dosage in the range of about 0.02 to 0.7 mg/kg.

3. A therapeutic method for increasing contractility of the mammalian heart as shown by a positive inotropic effect which comprises administering to a mammal in need thereof in an amount effective to cause a positive inotropic effect, a composition which comprises a biologically acceptable carrier and a compound selected from the group consisting of tetrahydropalmatine and its pharmaceutically acceptable salts thereof, causing a positive inotropic effect and discontinuing administration.

4. The therapeutic method of claim 3 wherein the compound is administered periodically.

5. A therapeutic method for increasing contractility of the mammalian heart as shown by a positive inotropic effect which comprises administering to a mammal in need thereof a composition which comprises a pharmaceutically acceptable carrier and a cardiac glycoside and in conjunction therewith, in an amount effective to cause a positive inotropic effect, a composition which comprises a pharmaceutically acceptable carrier and a compound selected from the group consisting of berberrubine, tetrahydropalmatine and the pharmaceutically acceptable salts thereof, causing a positive inotropic effect.

6. The therapeutic method of claim 5 wherein the compound is administered periodically.

7. The therapeutic method of claim 5 wherein the compound is berberrubine or its pharmaceutically acceptable salts.

8. The therapeutic method of claim 5 wherein the compound is tetrahydropalmatine or its pharmaceutically acceptable salts.

9. The therapeutic method of claim 5, 6, 7 or 8 wherein the cardiac glycoside is selected from the group consisting of ouabain, digoxin, digitoxin and delanoside.

15. The method of claim 5 wherein the compound is administered in a dosage in the range of about 0.001 to about 50 mg/kg.

16. The method of claim 5 wherein the compound is administered in a dosage in the range of about 0.02 to about 0.7 mg/kg.

10. A therapeutic method for increasing contractility of the mammalian heart as shown by a positive inotropic effect which comprises administering to a mammal in need thereof a composition which comprises a pharmaceutically acceptable carrier and a cardiac glycoside and in conjunction therewith, in an amount effective to cause a positive inotropic effect, a composition which comprises a pharmaceutically acceptable carrier and a compound selected from the group consisting of berberine and the pharmaceutically acceptable salts thereof, causing a positive inotropic effect and discontinuing the administration of the composition comprising the cardiac glycoside and the compositiion comprising the compound.

11. The therapeutic method of claim 10 wherein the compound is administered periodically.

12. The therapeutic method of claim 10 or 11 wherein the cardiac glycoside is selected from the group consisting of ouabain, digoxin, digitoxin and delanoside.

17. The method of claim 10 wherein the compound is administered in a dosage in the range of about 0.001 to about 50 mg/kg.

18. The method of claim 10 wherein the compound is administered in a dosage in the range of about 0.02 to 0.7 mg/kg.