Methods and compositions for noninvasive dose-to-effect administration of drugs with cardiovascular or renal vascular activities

• US 4,885,173 A
• Filed: 06/08/1987
• Issued: 12/05/1989
• Est. Priority Date: 05/01/1985
• Status: Expired due to Term

• Current Assignee: University of Utah Research Foundation Salt Lake City Utah
• Original Assignee: University of Utah (State of Utah)
• Inventors: Hague, Brian, Stanley, Theodore H.
• Primary Examiner(s): Page, Thurman K.
• Application Number:
  US07/060,046
• Time in Patent Office: 911 Days
• Field of Search: 424/440, 424/439, 424/441
• US Class Current: 424/440
• CPC Class Codes: A23G 3/368 containing vitamins, antibiotics
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals

Claims

1. A method for administering a potent drug capable of inducing rapidly a predetermined systemic modification of cardiovascular or renal vascular functions in a patient, the method comprising the steps of:

obtaining a soluble matrix material in the form of a lollipop into which the potent drug has been dispersed, said soluble matrix material being capable of releasing the drug for absorption through mucosal tissues of the mouth, pharynx, and esophagus;

providing the drug-containing lollipop to the patient to whom the drug is to be administered in order to induce rapidly the predetermined systemic modification of the cardiovascular or renal vascular functions of the patient;

administering the drug-containing lollipop to the patient in a manner such that the lollipop is dissolved so that the drug is absorbed through the mucosal tissues of the mouth, pharynx, and esophagus, thereby entering the patient'"'"'s bloodstream, said administering step being accomplished in a dose-to-effect manner;

controlling the rate of dissolution of the drug-containing lollipop in a dose-to-effect manner in order to obtain the predetermined systemic modification of cardiovascular or renal vascular functions of the patient while accounting for the patient'"'"'s susceptibility to the cardiovascular or renal vascular drug and the patient'"'"'s individual subjective experience of the cardiovascular or renal vascular functions; and

modifying the rate of dissolution of the drug-containing lollipop in response to the predetermined systemic modifications of cardiovascular or renal vascular functions of the patient.

2. A method for administering a drug as defined in claim 1, wherein the patient is initially caused to suck on the drug-containing lollipop in a manner capable of effecting rapid dissolution thereof, such that relatively high quantities of drug are absorbed into the patient'"'"'s bloodstream in order to rapidly obtain the desired systemic modification of cardiovascular functions of the patient, and wherein the patient is thereafter caused to suck on the drug-containing lollipop only as needed to maintain such desired cardiovascular effect.

3. A method for administering a drug as defined in claim 2, wherein the drug-containing lollipop is maintained relatively passively in the patient'"'"'s mouth after the desired effect is obtained in order to maintain such desired effect.

4. A method for administering a drug as defined in claim 1, wherein the drug in the drug-containing lollipop is an antiarrythmic agent and wherein the drug-containing lollipop is administered to the patient in a dose-to-effect manner until the patient'"'"'s heartbeat becomes regular.

5. A method for administering a drug as defined in claim 1, wherein the drug in the drug-containing lollipop is a hypotensive agent, and wherein the drug-containing lollipop is administered to the patient in a dose-to-effect manner until the patient'"'"'s blood pressure is lowered to the desired level.

6. A method for administering a drug as defined in claim 1, wherein the drug in the drug-containing lollipop is a vasodilator.

7. A method for administering a drug as defined in claim 1, wherein the drug in the drug-containing lollipop is an anti-anginal agent, and wherein the drug-containing lollipop is administered in a dose-to-effect manner until the patient'"'"'s pain from the angina is substantially eliminated.

8. A method for administering a drug as defined in claim 1, wherein the drug in the drug-containing lollipop is an inotropic agent.

9. A method for administering a drug as defined in claim 1, wherein the drug in the drug-containing lollipop is a calcium channel blocking agent which, when administered in a dose-to-effect manner, is an antiarrythmic, hypotensive, vasodilator, and anti-anginal agent.

10. A method for administering a drug as defined in claim 1, wherein the drug in the drug-containing lollipop is an organic nitrate which, when administered in a dose-to-effect manner, is a hypotensive, vasodilator, and anti-anginal agent.

11. A method for administering a drug as defined in claim 1, wherein the drug in the drug-containing lollipop is a beat-adrenergic blocking agent which, when administered in a dose-to-effect manner, is an antiarrythmic, hypotensive, and anti-anginal agent.

12. A method for administering a drug as defined in claim 4, wherein the antiarrythmic agent is bretylium and the dosage of bretylium dispersed in the matrix is in the range from about 50 milligrams to about 500 milligrams of bretylium equivalent.

13. A method for administering a drug as defined in claim 4, wherein the antiarrythmic agent is lidocaine and the dosage of lidocaine dispersed in the matrix is in the range from about 50 milligrams to about 250 milligrams of lidocaine equivalent.

14. A method for administering a drug as defined in claim 5, wherein the hypotensive drug is prazosin and the dosage of prazosin dispersed in the matrix is in the range from about 2 milligrams to about 10 milligrams of prazosin equivalent.

15. A method for administering a drug as defined in claim 5, wherein the hypotensive drug is labetolol and the dosage of labetolol dispersed in the matrix is in the range from about 100 milligrams to about 400 milligrams of labetolol equivalent.

16. A method for administering a drug as defined in claim 5, wherein the hypotensive drug is methyldopa and the dosage of methyldopa dispersed in the matrix is in the range from about 250 milligrams to about 750 milligrams of methyldopa equivalent.

17. A method for administering a drug as defined in claim 5, wherein the hypotensive drug is nitroprusside and the dosage of nitroprusside dispersed in the matrix is in the range from about 10 milligrams to about 50 milligrams of nitroprusside equivalent.

18. A method for administering a drug as defined in claim 5, wherein the hypotensive drug is clonidine and the dosage of clonidine dispersed in the matrix is in the range from about 0.1 milligrams to about 0.5 milligrams of clonidine equivalent.

19. A method for administering a drug as defined in claim 5, wherein the hypotensive drug is hydralazine and the dosage of hydralazine dispersed in the matrix is in the range from about 10 milligrams to about 75 milligrams of hydralazine equivalent.

20. A method for administering a drug as defined in claim 5, wherein the hypotensive drug is captopril and the dosage of captopril dispersed in the matrix is in the range from about 25 milligrams to about 75 milligrams of captopril equivalent.

21. A method for administering a drug as defined in claim 5, wherein the hypotensive drug is enalapril and the dosage of enalapril dispersed n the matrix is in the range from about 5 milligrams to about 15 milligrams of enalapril equivalent.

22. A method for administering a drug as defined in claim 11, wherein the beta-adrenergic blocking agent is esmolol and the dosage of esmolol dispersed in the matrix is in the range from about 25 milligrams to about 250 milligrams of esmolol equivalent.

23. A method for administering a drug as defined in claim 11, wherein the beta-adrenergic blocking agent is nadolol and the dosage of nadolol dispersed in the matrix is in the range from about 40 milligrams to about 160 milligrams of nadolol equivalent.

24. A method for administering a drug as defined in claim 11, wherein the beta-adrenergic blocking agent is pindolol and the dosage of pindolol dispersed in the matrix is in the range from about 5 milligrams to about 15 milligrams of pindolol equivalent.

25. A method for administering a drug as defined i claim 11, wherein the beta-adrenergic blocking agent is timolol and the dosage of timolol dispersed in the matrix is in the range from about 10 milligrams to about 50 milligrams of timolol equivalent.

26. A method for administering a drug as defined in claim 11, wherein the beta-adrenergic blocking agent is atenolol and the dosage of atenolol dispersed in the matrix is in the range from about 50 milligrams to about 150 milligrams of atenolol equivalent.

27. A method for administering a drug as defined in claim 11, wherein the beat-adrenergic blocking agent is metoprolol and the dosage of metoprolol dispersed in the matrix is in the range from about 25 milligrams to about 100 milligrams of metoprolol equivalent.

28. A method for administering a drug as defined in claim 9, wherein the calcium channel blocking agent is diltiazem and the dosage of diltiazem dispersed in the matrix is in the range from about 30 milligrams to about 120 milligrams of diltiazem equivalent.

29. A method for administering a drug as defined in claim 9, wherein the calcium channel blocking agent is nifedipine and the dosage of nifedipine dispersed in the matrix is in the range from about 10 milligrams to about 40 milligrams of nifedipine equivalent.

30. A method for administering a drug as defined in claim 9, wherein the calcium channel blocking agent is verapamil and the dosage of verapamil dispersed in the matrix is in the range from about 80 milligrams to about 240 milligrams of verapamil equivalent.

31. A method for administering a drug as defined in claim 10, wherein the organic nitrate drug is isosorbide and the dosage of isosorbide dispersed in the matrix is in the range from about 2.5 milligrams to about 40 milligrams of isosorbide equivalent.

32. A method for administering a drug as defined in claim 8, wherein the inotropic drug is amrinone and the dosage of amrinone dispersed in the matrix is in the range from about 50 milligrams to about 100 milligrams of amrinone equivalent.

33. A method for administering a drug as defined in claim 7, wherein the anti-anginal agent is esmolol and the dosage of esmolol dispersed in the matrix is in the range from about 25 milligrams to about 250 milligrams of esmolol equivalent.

34. A method for administering a drug as defined in claim 7, wherein the anti-anginal agent is nadolol and he dosage of nadolol dispersed in the matrix is in the range from about 40 milligrams to about 160 milligrams of nadolol equivalent.

35. A method for administering a drug as defined in claim 7, wherein the anti-anginal agent is pindolol and the dosage of pindolol dispersed in the matrix is in the range from about 5 milligrams to about 15 milligrams of pindolol equivalent.

36. A method for administering a drug as defined in claim 7, wherein the anti-anginal agent is timolol and the dosage of timolol dispersed in the matrix is in the range from about 10 milligrams to about 50 milligrams of timolol equivalent.

37. A method for administering a drug as defined in claim 7, wherein the anti-anginal agent is atenolol and the dosage of atenolol dispersed in the matrix is in the range from about 50 milligrams to about 150 milligrams of atenolol equivalent.

38. A method for administering a drug as defined in claim 7, wherein the anti-anginal agent is diltiazem and the dosage of diltiazem dispersed in the matrix is in the range from about 30 milligrams to about 120 milligrams of diltiazem equivalent.

39. A method for administering a drug as defined in claim 7, wherein the anti-anginal agent is nifedipine and the dosage of nifedipine dispersed in the matrix is in the range from about 10 milligrams to about 40 milligrams of nifedipine equivalent.

40. A method for administering a drug as defined in claim 7, wherein the anti-anginal agent is verapamil and the dosage of verapamil dispersed in the matrix is in the range from about 80 milligrams to about 240 milligrams of verapamil equivalent.

41. A method for administering a drug as defined in claim 7, wherein the anti-anginal agent is isosorbide and the dosage of isosorbide dispersed in the matrix is in the range from about 2.5 milligrams to about 50 milligrams of isosorbide equivalent.

42. A method for administering a drug as defined in claim 7, wherein the anti-anginal agent is metoprolol and the dosage of metoprolol dispersed in the matrix is in the range from 25 milligrams to about 100 milligrams of metoprolol equivalent.

43. A method for administering a drug as defined in claim 1, wherein the soluble matrix material in the drug-containing lollipop is a carbohydrate mass.

44. A method for administering a drug as defined in claim 1, wherein the soluble matrix material is a compressed carbohydrate mass.

45. A method for administering a drug as defined in claim 1, wherein the drug-containing lollipop is intermittently removed from the patient'"'"'s mouth in order to prevent an excessive amount of drug from being absorbed through the mucosal tissues into the patient'"'"'s bloodstream.

46. A method for administering a drug as defined in claim 1, wherein the drug-containing lollipop includes an inner matrix containing the drug in a suitable concentration for maintaining the desired cardiovascular effect, and an outer matrix covering the inner matrix, said outer matrix containing the drug in a suitable concentration for rapidly inducing the desired cardiovascular effect.

47. A method for administering a drug as defined in claim 1, wherein a first drug-containing lollipop is initially administered to the patient in order to rapidly induce a desired cardiovascular effect, and thereafter a second drug-containing lollipop is administered that is suitable for use in maintaining the desired cardiovascular effect.

48. A method for administering a drug as defined in claim 47, wherein the first drug-containing lollipop and the second drug-containing lollipop are of different colors in order to be easily distinguished from one another.

49. A method for administering a drug as defined in claim 1, wherein the drug in the drug-containing lollipop is dopamine and the dosage of dopamine dispersed in the matrix is in the range from about 350 micrograms to about 700 micrograms of dopamine equivalent.

51. A method for administering a drug as defined in claim 1, wherein the modifying step includes terminating the administration of the drug-containing lollipop in the patient.

52. A method for administering a drug as defined in claim 1, wherein the rate of dissolution of the drug-containing lollipop is under the control of a medical professional.

53. A method for administering a drug as defined in claim 1, wherein the rate of dissolution of the drug-containing lollipop is under the control of the patient.

50. A method for administering a drug capable of including rapidly a predetermined systemic modification of cardiovascular or renal vascular functions in a patient, the method comprising the steps of:

obtaining a soluble matrix material in the form of a lollipop into which the drug verapamil has been dispersed, said soluble matrix material being capable of releasing the drug verapamil for absorption through mucosal tissues of the mouth, pharynx, and esophagus;

providing the verapamil-containing lollipop to the patient to whom the verapamil is to be administered in order to induce rapidly the predetermined systemic modification of the cardiovascular or renal vascular functions of the patient;

administering the verapamil-containing lollipop to the patient in a manner such that the lollipop is dissolved so that the verapamil is absorbed through the mucosal tissues of the mouth, pharynx, and esophagus, thereby entering the patient'"'"'s bloodstream, said administering step being accomplished in a dose-to-effect manner; and

controlling the rate of dissolution of the verapamil-containing lollipop in a dose-to-effect manner in order to obtain the predetermined systemic modification of cardiovascular functions of the patient while accounting for the patient'"'"'s susceptibility to the verapamil and the patient'"'"'s individual subjective experience of the cardiovascular or renal vascular functions.