Controlled release drug delivery

• US 6,168,801 B1
• Filed: 03/19/1999
• Issued: 01/02/2001
• Est. Priority Date: 09/09/1998
• Status: Expired due to Term

• Current Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Original Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Inventors: KenKnight, Bruce H., Heil, Ronald W. Jr.
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US09/272,428
• Time in Patent Office: 655 Days
• Field of Search: 424/424, 424/425, 424/426, 514/772.3
• US Class Current: 424/426
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61P 9/06 Antiarrhythmics

Abstract

Biologically active materials are provided in a cylindrical carrier medium with better control over the rate of delivery and length of time of delivery by providing a carrier having dissolved or dispersed therein at least two compounds having a common biologically active nucleus, but with different solubility parameters. The combination of the two different variants of the same drug with different solubility parameters provides the material with control over the rate of release of the compounds (by varying the proportions of the variants) and most importantly, extending the useful life of the device by enabling release of effective levels of the compounds over a longer period of time. The cylindrical carrier medium, comprised of silicone, further includes a tail, a skirt, or a rate-limiting membrane.

Claims

1. A material for delivering a biologically active compound comprising a solid carrier material having dissolved and/or dispersed therein at least two biologically active compounds, each of said at least two biologically active compounds having a biologically active nucleus which is common to each of the biologically active compounds, and the at least two biologically active compounds having maximum solubility levels in a single solvent which differ from each other by at least 10% by weight;

wherein said solid carrier comprises a biocompatible polymeric material.

3. The material of claim 1 wherein said solvent comprises distilled, deionized water at 37 degrees Centigrade.

6. The material of claim 1 wherein the at least two biologically active compounds comprise compounds having a common biologically active nucleus with each of said at least two biologically active compounds having different substituents groups thereon, the different substituent groups providing, at least in part, different solubility characteristics to the at least two biologically active compounds.

2. A material for delivering a medically active compound comprising a solid carrier material having dissolved and/or dispersed therein at least two medically active compounds, each of said at least two medically active compounds having a medically active nucleus which is common to each of the medically active compounds, and the at least two medically active compounds having maximum solubility levels in a single solvent which differ from each other by at least 10% by weight;

wherein said solid carrier comprises a biocompatible polymeric material.

4. The material of claim 2 wherein said solvent comprises distilled, deionized water at 37 degrees Centigrade.

5. The material of claim 2 wherein said solvent comprises a bodily fluid at 37 degrees Centigrade.

7. The material of claim 2 wherein the at least two medically active compounds comprise compounds having a common medically active nucleus with each of said at least two medically active compounds having different substituents groups thereon, the different substituent groups providing, at least in part, different solubility characteristics to the at least two medically active compounds.

8. The material of claim 2 wherein the at least two medically active compounds comprise compounds having a common medically active nucleus with each of said at least two medically active compounds having different substituents groups thereon, the different substituent groups providing, at least in part, different solubility characteristics to the at least two medically active compounds.

9. The material of claim 4 wherein the at least two medically active compounds comprise compounds having a common medically active nucleus with each of said at least two medically active compounds having different substituents groups thereon, the different substituent groups providing, at least in part, different solubility characteristics to the at least two medically active compounds.

16. A surgically implantable device having attached thereto the material of claim 2.

10. A process for delivery of a biologically active ingredient to a patient comprising:

providing an article for delivering a medically active compound comprising a solid carrier material having dissolved and/or dispersed therein at least two medically active compounds, wherein said solid carrier comprises a biocompatible polymeric material, each of said at least two medically active compounds having a medically active nucleus which is common to each of the medically active compounds, and the at least two medically active compounds having maximum solubility levels in a single solvent which differ from each other by at least 10% by weight, and

implanting said article into a patient.

11. The process of claim 10 wherein said biologically active ingredient is a medically active ingredient.

12. The process of claim 10 wherein said solvent comprises distilled, deionized water at 37 degrees Centigrade.

13. The process of claim 11 wherein said solvent comprises a bodily fluid at 37 degrees Centigrade.

14. The process of claim 12 wherein the at least two medically active compounds comprise compounds having a common biologically active nucleus with each of said at least two medically active compounds having different substituent groups thereon, the different substituent groups providing, at least in part, different solubility characteristics to the at least two medically active compounds.

15. The process of claim 11 wherein the at least two medically active compounds comprise compounds having a common medically active nucleus with each of said at least two medically active compounds having different substituents groups thereon, the different substituent groups providing, at least in part, different solubility characteristics to the at least two medically active compounds.

17. A drug delivery device comprising:

a solid carrier material having loaded therein at least two medically active compounds, each of said at least two medically active compounds having a medically active nucleus which is common to each of the medically active compounds, and the at least two medically active compounds having maximum solubility levels in a single solvent which differ from each other by at least 10% by weight; and

the solid carrier comprising a cylinder formed of a biocompatible polymeric material.

18. The drug delivery device as recited in claim 17, further comprising a rate limiting membrane disposed on a portion of the cylinder.

19. The drug delivery device as recited in claim 17, wherein the cylinder is fully encapsulated by a rate limiting membrane.

20. The drug delivery device as recited in claim 17, wherein the carrier has a rapid release portion and a sustained release portion.

21. The drug delivery device as recited in claim 17, further comprising a tail coupled with a portion of the cylinder.

22. The drug delivery device as recited in claim 21, wherein the tail is formed of a material which is identifiable by x-ray.

23. The drug delivery device as recited in claim 17, wherein the cylinder has a length of 2-10 centimeters.

24. The drug delivery device as recited in claim 17, wherein the cylinder has a diameter of 2-5 millimeters.

25. The drug delivery device as recited in claim 17, further comprising a skirt coupled with the cylinder.

26. The drug delivery device as recited in claim 17, wherein a first compound comprises dexamethasone sodium phosphate (DSP), and a second compound comprises dexamethasone acetate (DA).

27. The drug delivery device as recited in claim 26, wherein the carrier has about 75% DSP and about 25% DA.

28. The drug delivery device as recited in claim 26, wherein the carrier has about 25% DSP and about 75% DA.

29. The drug delivery device as recited in claim 26, wherein the carrier has about 50% DSP and about 50% DA.

30. The drug delivery device as recited in claim 17, wherein the solid carrier is formed of silicone.

31. A drug delivery device comprising:

a solid carrier material having loaded therein at least two medically active compounds, each of said at least two medically active compounds having a medically active nucleus which is common to each of the medically active compounds, and the at least two medically active compounds having maximum solubility levels in a single solvent which differ from each other by at least 10% by weight;

a first medically active compound comprising dexamethasone sodium phosphate (DSP), and a second medically active compound comprises dexamethasone acetate (DA);

the solid carrier comprising a cylinder formed of a biocompatible polymeric material including silicone, the carrier having a rate limiting membrane disposed on at least a portion of the cylinder; and

the cylinder having a length of 2-10 centimeters, and a diameter of 2-5 millimeters.

32. A drug delivery device comprising:

a solid carrier material of biocompatible polymeric material, the solid carrier material having loaded therein at least two medically active compounds, each of said at least two medically active compounds having a medically active nucleus which is common to each of the medically active compounds, and the at least two medically active compounds having maximum solubility levels in a single solvent which differ from each other by at least a factor of approximately two when measured as percent by weight.

33. The drug delivery device as recited in claim 32, wherein the at least two medically active compounds have an efficacy in tachyarrhythmia therapy.

34. A drug delivery device comprising:

a solid carrier material of biocompatible polymeric material, the solid carrier material having loaded therein at least two medically active compounds, each of said at least two medically active compounds having a medically active nucleus which is common to each of the medically active compounds;

wherein a first medically active compound is generally hydrophilic and a second medically active compound is generally hydrophobic.

35. A drug delivery device comprising:

a solid carrier material of biocompatible polymeric material, the solid carrier material having loaded therein at least two medically active compounds, each of said at least two medically active compounds having a medically active nucleus which is common to each of the medically active compounds;

wherein a first medically active compound is generally soluble in an aqueous solvent and a second medically active compound is generally insoluble in the aqueous solvent.

36. The drug delivery device as recited in claim 35, wherein the aqueous solvent is a bodily fluid at approximately 37 degrees Centigrade.

37. The drug delivery device as recited in claim 35, wherein the at least two medically active compounds have an efficacy in tachyarrhythmia therapy.

38. A process for delivering a medically active nucleus to a patient comprising:

implanting an article into the patient, wherein the article comprises a solid carrier material of biocompatible polymeric material, the solid carrier material having loaded therein at least two medically active compounds, each of said at least two medically active compounds having the medically active nucleus, and the at least two medically active compounds having maximum solubility levels in a bodily fluid which differ from each other by at least 10% by weight.

39. The process as recited in claim 38, wherein the bodily fluid is blood at approximately 37 degrees Centigrade.

40. The process as recited in claim 38, wherein the medically active nucleus has an efficacy in tachyarrhythmia therapy.

41. A process for delivering a medically active nucleus to a patient comprising:

implanting an article into the patient, wherein the article comprises a solid carrier material of biocompatible polymeric material, the solid carrier material having loaded therein at least two medically active compounds, each of said at least two medically active compounds having the medically active nucleus, and the at least two medically active compounds having maximum solubility levels in a bodily fluid which differ from each other by at least a factor of approximately two when measured as percent by weight.

42. A process for delivering a medically active nucleus to a patient comprising:

implanting an article into the patient, wherein the article comprises a solid carrier material of biocompatible polymeric material, the solid carrier material having loaded therein at least two medically active compounds, each of said at least two medically active compounds having the medically active nucleus, wherein a first medically active compound is generally hydrophilic and a second medically active compound is generally hydrophobic.

43. A process for delivering a medically active nucleus to a patient comprising:

implanting an article into the patient, wherein the article comprises a solid carrier material of biocompatible polymeric material, the solid carrier material having loaded therein at least two medically active compounds, each of said at least two medically active compounds having the medically active nucleus, wherein a first medically active compound is generally soluble in a bodily fluid and a second medically active compound is generally insoluble in the bodily fluid.