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

• US 9,022,022 B2
• Filed: 01/13/2014
• Issued: 05/05/2015
• 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): Bosworth, Kami A
• Assistant Examiner(s): HAYMAN, IMANI N
• Application Number:
  US14/153,575
• Publication Number:
  US 20140123974A1
• Time in Patent Office: 477 Days
• US Class Current: 128/200.14
• 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 disposed within the housing, the medicament container containing a naloxone composition;

an elastomeric member movably disposed within the medicament container, the elastomeric member formulated to be compatible with the naloxone composition, at least a portion of the elastomeric member including a silicone-based material; and

an energy storage member disposed within the housing, the energy storage member configured to produce a force that is exerted on the elastomeric member to deliver the naloxone composition,

wherein the naloxone composition includes naloxone or salts thereof, a tonicity-adjusting agent, and a pH adjusting agent, whereby at least one of (A) the osmolality of the naloxone composition ranges from about 250-350 mOsm or (B) the pH ranges from about 3-5.

2. The apparatus of claim 1, wherein the pH adjusting agent is present in the naloxone composition in an amount sufficient to cause the pH of the naloxone composition to be within the range from 3-5.

3. The apparatus of claim 1, wherein the naloxone composition includes 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl) morphinan-6-one.

4. The apparatus of claim 1, wherein the tonicity-adjusting agent includes at least one of dextrose, glycerin, mannitol, potassium chloride or sodium chloride.

5. The apparatus of claim 1, wherein the tonicity-adjusting agent includes sodium chloride in an amount such that a concentration of sodium chloride is between approximately 0.1 mg/mL and approximately 20 mg/mL.

6. The apparatus of claim 1, wherein the elastomeric member is formulated to include a polymer and a curing agent, the polymer including at least one of bromobutyl or chlorobutyl, the curing agent including at least one of sulfur or a metal oxide.

7. The apparatus of claim 1, wherein at least a portion of the elastomeric member is coated with polydimethylsiloxane.

8. The apparatus of claim 1, wherein at least the portion of the elastomeric member is coated with polydimethylsiloxane in an amount of between approximately 0.02 mg/cm² and approximately 0.80 mg/cm².

9. The apparatus of claim 1, further comprising:

an electronic circuit system coupled to the housing, the electronic circuit system configured to produce an output when the electronic circuit system is actuated.

10. The apparatus of claim 1, further comprising:

a delivery member coupled to the medicament container, the naloxone composition configured to be delivered from the medicament container via the delivery member.

11. The apparatus of claim 10, wherein the delivery member is a needle defining a lumen therein having a size of between 19 gauge and 31 gauge.

12. The apparatus of claim 10, wherein the delivery member is an atomizer configured to atomize the naloxone composition.

13. An apparatus, comprising:

a housing;

a medicament container disposed within the housing, the medicament container containing a naloxone composition;

a plunger movably disposed within the medicament container, at least a portion of the plunger including polydimethylsiloxane such that the portion of the plunger is compatible with the naloxone composition; and

an energy storage member disposed within the housing, the energy storage member configured to produce a force that is exerted on the plunger to deliver the naloxone composition,

wherein the naloxone composition includes naloxone or salts thereof, a tonicity-adjusting agent, and a pH adjusting agent, whereby at least one of (A) the osmolality of the naloxone composition ranges from about 250-350 mOsm or (B) the pH ranges from about 3-5.

14. The apparatus of claim 13, wherein the plunger is an elastomeric member.

15. The apparatus of claim 13, wherein the plunger is an elastomeric member formulated to include a polymer and a curing agent, the polymer including at least one of bromobutyl or chlorobutyl, the curing agent including at least one of sulfur or a metal oxide.

16. The apparatus of claim 13, wherein at least the portion of the plunger is coated with polydimethylsiloxane in an amount of between approximately 0.02 mg/cm² and approximately 0.80 mg/cm².

17. The apparatus of claim 13, wherein the tonicity-adjusting agent includes at least one of dextrose, glycerin, mannitol, potassium chloride or sodium chloride.

18. An apparatus, comprising:

a housing;

a medicament container assembly disposed within the housing, the medicament container assembly including;

a naloxone composition including a tonicity-adjusting agent and a pH adjusting agent, the pH of the naloxone composition ranges from about 3-5;

a silicone-based material such that the medicament container assembly is compatible with the naloxone composition; and

a plunger; and

an actuator moveably coupled to the housing, the actuator configured to cause a force to be exerted on the plunger to expel the naloxone composition from the medicament container assembly when the actuator is moved relative to the housing.

19. The apparatus of claim 18, wherein the pH of the naloxone composition ranges from about 3.2-3.6.

20. The apparatus of claim 18, wherein the medicament container assembly includes a seal, the apparatus further comprising:

a delivery member configured to be coupled to the medicament container assembly, the naloxone composition configured to be expelled from the medicament container assembly via the delivery member, the seal configured to fluidically isolate the delivery member from the medicament container assembly before the actuator is moved relative to the housing, the delivery member configured to be placed in fluid communication with the medicament container assembly when the plunger moves relative to the medicament container.

21. The apparatus of claim 20 wherein the delivery member is configured to atomize the naloxone composition.

22. An apparatus, comprising:

a medicament container containing a naloxone composition, the naloxone composition including naloxone or salts thereof, a tonicity-adjusting agent, and a pH adjusting agent, whereby the pH of the naloxone composition ranges from about 3-5;

an elastomeric member configured to be disposed within the medicament container and configured to be in contact with the naloxone composition, the elastomeric member including a silicone-based material;

a carrier including a needle, the carrier configured to receive at least a distal end portion of the medicament container such that an end portion of the needle is fluidically isolated from the medicament container when the medicament container is in a first position within the carrier, the end portion of the needle being in fluid communication with the medicament container when the medicament container is in a second position within carrier; and

a movable member configured to exert a force on the elastomeric member to move the medicament container from the first position to the second position, and to deliver the naloxone composition via the needle.

23. The apparatus of claim 22, further comprising:

an energy storage member disposed within the housing, the energy storage member configured to produce the force.

24. The apparatus of claim 22, wherein the elastomeric member is a flexible wall configured to exert a force on the naloxone composition, the naloxone composition being expelled from the medicament container when the force is exerted.

25. The apparatus of claim 22, wherein at least a portion of the elastomeric member includes polydimethylsiloxane.

26. The apparatus of claim 22, wherein the carrier includes an atomizer configured to atomize the naloxone composition.