Medicament delivery device for administration of opioid antagonists including formulations for naloxone

• US 9,474,869 B2
• Filed: 04/23/2015
• Issued: 10/25/2016
• Est. Priority Date: 02/28/2011
• Status: Active Grant

• Current Assignee: Kaleo, Inc.
• Original Assignee: Kaleo, Inc.
• Inventors: Edwards, Eric S., Edwards, Evan T., Licata, Mark J., Blondino, Frank E.
• Primary Examiner(s): HAYMAN, IMANI N
• Application Number:
  US14/694,725
• Publication Number:
  US 20150297840A1
• Time in Patent Office: 551 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61M 11/00 Sprayers or atomisers specially adapted for therapeutic purposes in general B05B; aerosol containers B65D83/14
• CPC Class Codes: A61M 11/007 Syringe-type or piston-type sprayers or atomisers
• CPC Class Codes: A61M 15/0001 Details of inhalators; Constructional features thereof
• CPC Class Codes: A61M 15/08 Inhaling devices inserted into the nose
• CPC Class Codes: A61M 2202/048 Anaesthetics see also A61M19/00
• CPC Class Codes: A61M 2205/14 Detection of the presence or absence of a tube, a connector or a container in an apparatus
• CPC Class Codes: A61M 2205/3584 using modem, internet or bluetooth
• CPC Class Codes: A61M 2205/581 by audible feedback
• CPC Class Codes: A61M 2205/583 by visual feedback
• CPC Class Codes: A61M 2205/80 voice-operated command
• CPC Class Codes: A61M 2205/8206 battery-operated
• CPC Class Codes: A61M 2209/06 Packaging for specific medical equipment
• CPC Class Codes: A61M 2210/0618 Nose
• CPC Class Codes: A61M 5/002 Packages specially adapted therefor, e.g. for syringes or needles, kits for diabetics needle protection, e.g. caps, A61M5/3202; for sharps A61B50/3001
• CPC Class Codes: A61M 5/2033 Spring-loaded one-shot injectors with or without automatic needle insertion multishot dosing syringes A61M5/31525, needle insertion only A61M5/3287
• CPC Class Codes: A61M 5/2046 Media being expelled from injector by gas generation, e.g. explosive charge
• CPC Class Codes: A61M 5/2459 upon internal pressure increase, e.g. pierced or burst A61M5/2429 takes precedence
• CPC Class Codes: A61M 5/3232 Semi-automatic needle retraction, i.e. in which triggering of the needle retraction requires a deliberate action by the user, e.g. manual release of spring-biased retraction means
• CPC Class Codes: A61M 5/5086 for indicating if defective, used, tampered with or unsterile
• CPC Class Codes: G09B 19/24 : Use of tools
• CPC Class Codes: G09B 5/04 : with audible presentation of the material to be studied sound recording or reproducing G11B

Abstract

Medicament delivery devices for administration of opioid antagonists are described herein. In some embodiments, an apparatus includes a housing, a medicament container disposed within the housing and an energy storage member disposed within the housing. The medicament container is filled with a naloxone composition that includes naloxone or salts thereof, a tonicity-adjusting agent, and a pH adjusting agent, whereby the osmolality of the naloxone composition ranges from about 250-350 mOsm and the pH ranges from about 3-5. The energy storage member is configured to produce a force to deliver the naloxone composition.

Claims

1. An apparatus, comprising:

a housing;

a medicament container assembly at least partially disposed within the housing, the medicament container assembly including a container body and an elastomeric member, the container body containing a naloxone composition, the naloxone composition including a tonicity-adjusting agent and a pH adjusting agent, the pH of the naloxone composition ranging from 3 to 5, the elastomeric member disposed within an internal volume of the container body, the elastomeric member including a silicone-based material;

a delivery member coupled to a coupling member disposed within the housing, the delivery member being fluidically isolated from the internal volume of the container body when the coupling member and the medicament container assembly are in a first configuration, the delivery member in fluid communication with the internal volume of the container body when the coupling member and the medicament container assembly are in a second configuration; and

an actuator coupled to the housing, the actuator configured to cause a force to be exerted to (1) transition the coupling member and the medicament container assembly from the first configuration to the second configuration and (2) deliver a single dose of the naloxone composition from the internal volume of the container body via the delivery member.

2. The apparatus of claim 1, wherein the medicament container assembly is configured to move relative to the coupling member when the coupling member and the medicament container assembly are transitioned from the first configuration to the second configuration.

3. The apparatus of claim 1, wherein the delivery member is a needle, an end portion of the needle being disposed outside of the internal volume of the container body when the coupling member and the medicament container assembly are in the first configuration, the end portion of the needle disposed within the internal volume of the container body when the coupling member and the medicament container assembly are in the second configuration.

4. The apparatus of claim 3, wherein the needle has a size between 19 gauge and 31 gauge.

5. The apparatus of claim 1, wherein the delivery member is associated with an atomizer defining an orifice through which the naloxone composition is delivered intranasally to a patient.

6. The apparatus of claim 1, wherein the delivery member is an atomizer configured to produce a spray of the naloxone composition having a droplet size distribution in which 85 percent of the droplets have a size of between 10 microns and 150 microns.

7. The apparatus of claim 1, wherein movement of the actuator relative to the housing causes the force to be exerted on the medicament container assembly to (1) move the medicament container assembly relative to the coupling member, and (2) move the elastomeric member within the container body to convey the naloxone composition from the internal volume of the container body via the delivery member.

8. The apparatus of claim 1, wherein:

the delivery member is a needle, an end portion of the needle being disposed outside of the internal volume of the container body when the coupling member and the medicament container assembly are in the first configuration, the end portion of the needle disposed within the internal volume of the container body when the coupling member and the medicament container assembly are in the second configuration; and

the delivery member defines a part of a flow path through which the naloxone composition is delivered, the flow path in fluid communication with an orifice through which the naloxone composition is delivered intranasally to a patient.

9. The apparatus of claim 8, wherein:

the tonicity-adjusting agent includes sodium chloride in an amount such that a concentration of sodium chloride is between 0.1 mg/mL and 20 mg/mL.

10. The apparatus of claim 9, wherein the naloxone composition is in an amount such that a concentration of the naloxone composition is between 0.01 mg/mL and 60 mg/mL.

11. The apparatus of claim 1, wherein at least a portion of the elastomeric member is coated with the silicone-based material.

12. The apparatus of claim 1, wherein:

the delivery member is a needle, an end portion of the needle being disposed outside of the internal volume of the container body when the coupling member and the medicament container assembly are in the first configuration, the end portion of the needle disposed within the internal volume of the container body when the coupling member and the medicament container assembly are in the second configuration; and

a distal end portion of the housing defines an opening through which the naloxone composition is delivered.

13. The apparatus of claim 1, wherein:

the delivery member is a needle, an end portion of the needle being disposed outside of the internal volume of the container body when the coupling member and the medicament container assembly are in the first configuration, the end portion of the needle disposed within the internal volume of the container body when the coupling member and the medicament container assembly are in the second configuration; and

a distal end portion of the container body includes a shoulder.

14. A method, comprising:

removing a medicament delivery device from a case, the medicament delivery device including a medicament container assembly, a coupling member, and a delivery member, the medicament container assembly including a container body and an elastomeric member, the container body defining an internal volume containing a naloxone composition, the naloxone composition including a tonicity-adjusting agent and a pH adjusting agent, the pH of the naloxone composition ranging from 3 to 5, the elastomeric member disposed within the internal volume of the container body, the elastomeric member including a silicone-based material, the delivery member coupled to the coupling member such that the delivery member is fluidically isolated from the internal volume of the container body;

placing a distal end portion of the medicament delivery device into a position relative to a target location of a patient; and

actuating the medicament delivery device to (1) cause the medicament container assembly to move distally to place the delivery member in fluid communication with the internal volume of the container body and (2) convey a single dose of the naloxone composition from the internal volume via the delivery member.

15. The method of claim 14, wherein:

the delivery member is coupled to the medicament container assembly via the coupling member prior to the medicament delivery device being removed from the case; and

the actuating causes the medicament container assembly to move relative to the coupling member to place the delivery member in fluid communication with the internal volume of the container body.

16. The method of claim 14, wherein:

the delivery member is a needle coupled to the medicament container assembly via the coupling member, the coupling member and the medicament container assembly being in a first configuration prior to the removing, an end portion of the needle being disposed outside of the internal volume of the container body when the coupling member and the medicament container assembly are in the first configuration; and

the actuating causes the coupling member and the medicament container assembly to transition to a second configuration in which the end portion of the needle is within the internal volume of the container body.

17. The method of claim 14, wherein:

the target location of the patient is a nostril; and

the distal end portion of the medicament delivery device defines an orifice through which the naloxone composition is delivered intranasally to the patient.

18. The method of claim 14, wherein:

the delivery member is coupled to the medicament container assembly via the coupling member prior to the medicament delivery device being removed from the case; and

the actuating includes manually depressing an actuator to move the medicament container assembly relative to the coupling member to place the delivery member in fluid communication with the internal volume of the container body.

19. The method of claim 14, wherein:

the delivery member is coupled to the medicament container assembly via the coupling member prior to the medicament delivery device being removed from the case; and

the actuating includes manually depressing an actuator to exert a force to (1) move the medicament container assembly relative to the coupling member to place the delivery member in fluid communication with the internal volume of the container body, and (2) move the elastomeric member within the container body to convey the naloxone composition from the internal volume of the container body via the delivery member.

20. The method of claim 14, wherein:

the placing includes placing the distal end portion of the of the medicament delivery device in contact with a nostril, the distal end portion of the medicament delivery device defining an orifice; and

the actuating includes manually depressing an actuator to exert a force to move the elastomeric member within the container body to convey the naloxone composition through the orifice to the patient.

21. The method of claim 14, wherein the tonicity-adjusting agent includes at least one of dextrose, glycerin, mannitol, potassium chloride or sodium chloride.

22. The method of claim 14, further comprising:

storing, before the removing, the medicament delivery device within the case for at least six months.

23. The method of claim 14, wherein the medicament container assembly is configured to maintain the naloxone composition therein for at least one year.

24. The method of claim 14, wherein:

the target location of the patient is a nostril;

the delivery member is associated with an atomizer defining an orifice through which the naloxone composition is delivered intranasally to the patient, the atomizer being coupled to the medicament container assembly via the coupling member, the coupling member including a needle, the coupling member and the medicament container assembly being in a first configuration prior to the medicament delivery device being removed from the case, an end portion of the needle being disposed outside of the internal volume of the container body when the coupling member and the medicament container assembly are in the first configuration; and

the actuating includes manually depressing an actuator to move the medicament container assembly relative to the coupling member thereby causing the coupling member and the medicament container assembly to transition to a second configuration in which the end portion of the needle is within the internal volume of the container body.

25. The method of claim 24, wherein:

the tonicity-adjusting agent includes sodium chloride in an amount such that a concentration of sodium chloride is between 0.1 mg/mL and 20 mg/mL.

26. The method of claim 25, wherein the naloxone composition is in an amount such that a concentration of the naloxone composition is between 0.01 mg/mL and 60 mg/mL.

27. A method, comprising:

removing a medicament delivery device from a case, the medicament delivery device including a medicament container assembly, a coupling member and an atomizer, the medicament container assembly including a container body and an elastomeric member, the container body defining an internal volume containing a single dose of a naloxone composition, the naloxone composition including a tonicity-adjusting agent, the pH of the naloxone composition ranging from 3 to 5, the elastomeric member disposed within the internal volume of the container body, the elastomeric member including a silicone-based material, the atomizer coupled to the medicament container assembly via the coupling member;

placing a distal end portion of the medicament delivery device into a delivery position relative to a nostril of a patient; and

moving an actuator of the medicament delivery device to (1) cause the medicament container assembly to move relative to the coupling member to place the atomizer in fluid communication with the internal volume of the container body and (2) convey the single dose of the naloxone composition from the internal volume via the atomizer.

28. The method of claim 27, wherein the moving the actuator includes manually moving the actuator from a first position to a second position, the actuator being connected to the housing when in the first position.

29. The method of claim 27, wherein the moving the actuator includes manually moving the actuator to cause a force to be exerted on the medicament container assembly, a first portion of the force acting to move the medicament container assembly, a second portion of the force acting to move the elastomeric member within the container body to convey the naloxone composition.

30. The method of claim 27, wherein the moving the actuator includes manually squeezing the actuator.

31. The method of claim 27, wherein the moving the actuator includes manually pressing the actuator.

32. The method of claim 27, wherein the tonicity-adjusting agent includes at least one of dextrose, glycerin, mannitol, potassium chloride or sodium chloride.

33. The method of claim 27, wherein the naloxone composition is in an amount such that a concentration of the naloxone composition is between 0.01 mg/mL and 60 mg/mL, the tonicity-adjusting agent includes sodium chloride in an amount such that a concentration of sodium chloride is between 0.1 mg/mL and 20 mg/mL, the method further comprising:

storing, before the removing and with the atomizer coupled to the medicament container assembly via the coupling member, the medicament delivery device within the case for at least six months.

34. The method of claim 27, wherein the moving the actuator causes the atomizer to produce a spray of the naloxone composition having a droplet size distribution in which 85 percent of the droplets have a size of between 10 microns and 150 microns.

35. The method of claim 27, wherein:

the coupling member includes a needle, the coupling member and the medicament container assembly being in a first configuration prior to the removing, an end portion of the needle being disposed outside of the internal volume of the container body when the coupling member and the medicament container assembly are in the first configuration; and

the moving the actuator causes the coupling member and the medicament container assembly to transition to a second configuration in which the end portion of the needle is within the internal volume of the container body.

36. The method of claim 35, wherein the needle has a size between 19 gauge and 31 gauge.

37. An apparatus, comprising:

a housing;

a medicament container assembly at least partially disposed within the housing, the medicament container assembly including a container body and an elastomeric member, the container body containing a single dose of a naloxone composition, the naloxone composition including a tonicity-adjusting agent and a pH adjusting agent, the pH of the naloxone composition ranging from 3 to 5, the elastomeric member disposed within an internal volume of the container body, the elastomeric member including a silicone-based material;

an atomizer coupled to the medicament container assembly via a coupling member, the atomizer being fluidically isolated from the internal volume of the container body when the coupling member and the medicament container assembly are in a first configuration, the atomizer in fluid communication with the internal volume of the container body when the coupling member and the medicament container assembly are in a second configuration; and

an actuator coupled to the housing, the actuator configured to cause a force to be exerted to (1) transition the coupling member and the medicament container assembly from the first configuration to the second configuration and (2) deliver the single dose of the naloxone composition from the internal volume of the container body via the atomizer.

38. The apparatus of claim 37, wherein the medicament container assembly is configured to move relative to the coupling member when the coupling member and the medicament container assembly are transitioned from the first configuration to the second configuration.

39. The apparatus of claim 37, wherein the atomizer is coupled to a distal end portion of the housing and defines an orifice through which the naloxone composition is delivered intranasally to a patient.

40. The apparatus of claim 37, wherein:

the coupling member is associated with a needle, an end portion of the needle being disposed outside of the internal volume of the container body when the coupling member and the medicament container assembly are in the first configuration, the end portion of the needle disposed within the internal volume of the container body when the coupling member and the medicament container assembly are in the second configuration; and

the atomizer defines a part of a flow path through which the naloxone composition is delivered, the flow path in fluid communication with an orifice through which the naloxone composition is delivered intranasally to a patient.

41. The apparatus of claim 37, wherein:

the tonicity-adjusting agent includes sodium chloride in an amount such that a concentration of sodium chloride is between 0.1 mg/mL and 20 mg/mL.

42. The apparatus of claim 41, wherein the naloxone composition is in an amount such that a concentration of the naloxone composition is between 0.01 mg/mL and 60 mg/mL.