MULTIPLE IMPACT MICROPROJECTION APPLICATORS AND METHODS OF USE

• US 20140276366A1
• Filed: 03/10/2014
• Published: 09/18/2014
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Corium Pharma Solutions, Inc.
• Original Assignee: Corium International, Inc.
• Inventors: Bourne, Doug, Shastry, Ashutosh, Le, Anthony, Singh, Parminder
• Granted Patent: US 10,195,409 B2
• Time in Patent Office: Days
• US Class Current: 604/22
• CPC Class Codes: A61M 2005/1585 Needle inserters
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• CPC Class Codes: A61M 5/158 Needles for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body

Abstract

Applicators for a microprojection array capable of multiple impacts and methods of using the applicators are described.

Claims

1. A method of delivering a therapeutic agent to a subject, comprising:

applying to a skin site of a subject, an applicator comprising at least one plunger element, at least one microprojection retained on a distal surface of the plunger, and an actuator;

actuating the actuator to convey an external force to the at least one plunger element such that an energy required for the at least one microprojection to penetrate the skin site is delivered in multiple, discrete quanta and/or impacts.

2. The method of claim 1, wherein a maximum strain and/or strain rate is not exceeded by any of the multiple, discrete quanta and/or impacts.

3. The method of claim 1, further comprising delaying between impacts a sufficient time to allow a strain from a previous impact to dissipate.

4. The method of claim 1, wherein the at least one microstructure partially penetrates the skin site from a first impact, further comprising:

detaching the at least one microstructure from the plunger distal end.

5. The method of claim 1, wherein, the multiple, discrete quanta and/or impacts are created by one or more of:

(a) the plunger comprises multiple energy-mass systems, each system having a different time constant;

(b) the applicator comprises a plurality of plunger elements and an asynchronous release mechanism such that the plunger elements are released at different time periods;

(c) the applicator comprises a plurality of plunger elements each comprising a dashpot element having a different damping coefficient;

(d) the applicator comprises a plurality of plunger elements, each having a different type of spring; and

(e) the applicator further includes a vibration element.

6. The method of claim 5, wherein each of the energy-mass systems has a progressively higher time constant such that the plunger elements impact the skin site in a defined sequence.

7. The method of claim 1, wherein each energy-mass element includes a spring and a mass element, further comprising

adjusting a spring constant of one or more springs in the energy-mass elements to modify a delay in impact from the plunger elements.

8. The method of claim 7, further comprising:

adjusting a mass of the mass elements thereby to modify a delay in impact from the plunger elements.

9. The method of claim 5, further comprising:

controlling an amplitude of the vibration element to limit an impact strain from one or more of the multiple, discrete quanta and/or impacts.

10. The method of claim 5, controlling a frequency of the vibration element to limit an impact strain from one or more of the multiple, discrete quanta and/or impacts.

11. The method of claim 1, wherein the at least one plunger element contacts a subject'"'"'s skin with an energy of about 0.15-0.2 J.

12. An applicator, comprising:

at least a first plunger element comprising a first energy-mass system, the first plunger element having a first restrained position and a second extended position, the first plunger element comprising a distal end on which at least one microprojection can be retained;

at least a second energy-mass system;

wherein the first and second energy-mass systems each has a different time constant, and each energy-mass system has a first restrained position and a second extended position;

an actuating member that can convey an external force to at least the first plunger element to release the first plunger element from the first restrained position; and

at least one microstructure attached to a distal surface of the plunger element distal end.

13. The applicator of claim 12, wherein the first and second energy-mass systems each includes a mass and an energy-storing element.

14. The applicator of claim 13, wherein the energy-storing elements are elastic energy elements each selected from a compression spring, a coil spring, a wave spring, and a slotted spring.

15. The applicator of claim 12, wherein the first energy-mass system has a faster time constant than the second energy-mass system.

16. The applicator of claim 13, wherein the mass of the first energy-mass system is different than the mass of the second energy-mass system.

17. The applicator of claim 12, further comprising a third energy-mass system, wherein the third energy-mass system has a different time constant than the first or second energy-mass systems.

18. The applicator of claim 17, wherein the third energy-mass system has a slower time constant than the first or second energy-mass systems.

19. The applicator of claim 12, further comprising a housing member at least partially housing the first plunger element and actuating member.

20. The applicator of claim 12, wherein the at least one microprojection is a microprojection array comprising a plurality of microprojections.

21. The applicator of claim 20, wherein at least some of the plurality of microprojections are dissolvable or erodible microprojections.

22. The applicator of claim 20, wherein at least some of the plurality of microprojections include at least one therapeutic agent selected from a drug, a small molecule, a peptide or protein, or a vaccine.

23. The applicator of claim 20, wherein at least a portion of the plurality of microprojections are detachable from the microprojection array.

24. The applicator of claim 12, further comprising:

a damper positioned between at least one of the energy-storing elements and a proximal surface of the first plunger element distal end.

25. An applicator, comprising:

a plunger element comprising at least a shaft and a distal end on which at least one microprojection can be retained;

at least one projection positioned on a proximal surface of the plunger distal end, the plunger having a first restrained position and a second extended position;

an actuating member that can convey an external force to the plunger element to release the plunger element from the first restrained position;

a linear energy-storing member positioned between the actuator and the plunger distal end, the linear energy-storing member having a first position and a second position, wherein the linear energy-storing member is effective to move the plunger from its first position to its second position as the linear energy-storing member moves from its first position to its second position; and

a torsional energy-mass system at least partially surrounding the plunger shaft and being positioned between the linear energy-storing member and the plunger distal end, wherein the torsional energy-mass system contacts the at least one projection as the torsional energy-mass system rotates about the plunger shaft.

26. The applicator of claim 25, wherein the at least one projection comprises a plurality of projections spaced apart around the proximal surface of the plunger distal end.

27. The applicator of claim 25, wherein the energy-storing elements are each selected from a compression spring, a coil spring, and a wave spring.

28. The applicator of claim 25, wherein the at least one microprojection is a microprojection array comprising a plurality of microprojections.

29. The applicator of claim 28, wherein at least some of the plurality of microprojections are dissolvable or erodible microprojections.

30. The applicator of claim 28, wherein the plurality of microprojections includes at least one therapeutic agent selected from a drug, a small molecule, a peptide or protein, or a vaccine.

31. The applicator of claim 28, wherein at least a portion of the plurality of microprojections are detachable from the microprojection array.

32. The applicator of claim 25, further comprising:

a damper positioned between the energy-storage devices and a proximal surface of the plunger distal end.

33. A method of delivering a therapeutic agent to a subject, comprising:

applying to a skin site of the subject, an applicator according to claim 25;

actuating the actuating member to convey an external force to the plunger element;

releasing the plunger element from the first restrained position to the second extended position;

rotating the torsional energy-mass system about the plunger shaft such that the system contacts the at least one projection on the plunger proximal surface and pushes it downward as the system rotates about the plunger shaft thereby to move the plunger distal end toward the skin site.

34. The method of claim 33, wherein rotation of the torsional energy-mass system causes the plunger to impact the patient'"'"'s skin and causes the at least one microprojection to penetrate the skin further upon each impact.

35. The method of claim 34, wherein the plunger distal end comprises a plurality of projections spaced apart around the proximal surface of the plunger distal end and rotation of the torsional energy-mass system causes the plunger to impact the patient'"'"'s skin each time the system contacts one of the plurality of projections.