Intradermal injection system for injecting DNA-based injectables into humans

• US 6,319,224 B1
• Filed: 08/20/1999
• Issued: 11/20/2001
• Est. Priority Date: 08/20/1999
• Status: Expired due to Term

• Current Assignee: Bioject Incorporated
• Original Assignee: Bioject Medical Technologies Inc. (Inovio Pharmaceuticals, Inc.)
• Inventors: Miller, Robert A., Bonicatto, James M., Stout, Richard R.
• Primary Examiner(s): Kennedy, Sharon
• Assistant Examiner(s): WILLIAMS, CATHERINE SERKE
• Application Number:
  US09/378,294
• Time in Patent Office: 823 Days
• Field of Search: 604/68-72, 604/140-143, 604/187, 604/131
• US Class Current: 604/68
• CPC Class Codes: A61M 5/30 Syringes for injection by jet action, without needle, e.g. for use with replaceable ampoules or carpules

Abstract

A system for injecting DNA-based medications into humans is provided by the present invention. The system includes a needle-free injector with an injection orifice of approximately 0.004 inches for supplying DNA-based medication at an initial pressure of from 3900 to 4300 psi, and then immediately declining to a level of about 2800 to 3800 psi, and then immediately cutting off pressure to terminate the injection. The injector includes an annular adapter for spacing the injection orifice from the skin of the patient. The adapter includes an abutment against which the injector is disposed so that the orifice is spaced approximately 0.76-1.0 inch from the skin of the patient, the adapter having an inner diameter at the distal end of approximately 0.50-0.70 inches.

Claims

1. A method for performing intradermal injection of liquid injectables into humans, comprising:

fitting, adjacent an injection orifice of a needle-free injector, the proximal end of a substantially cylindrical intradermal adapter having a proximal and distal end and an internal abutment against which the injector is disposed to provide a fixed spacing of from approximately 0.76 to 1.0 inches from the injection orifice to the distal end of the adapter, the distal end having an inner diameter of from 0.50 to 0.70 inches;

selecting the needle-free injector having the injection orifice of from 0.004 to 0.005 inches;

holding the distal end of the intradermal adapter against the skin of the patient; and

using the needle-free injector to inject a liquid injectable in a volume of 0.3 ml or less into the intradermal region at an initial peak pressure of from 3900 to 4300 psi, and then permitting the injection pressure to decay to a level of about 2300 to 3800 psi, after which time the pressure is abruptly cut off, terminating the injection;

wherein, following a single quick drop and rebound in pressure following the initial peak pressure, there is no more than plus or minus 100 psi variation from the pressure curve of the injection.

2. A method of delivering liquid injectables intradermally, using a needle-free injection system, comprising the steps of:

pressurizing a liquid injectable within an ampule having a nozzle orifice to an initial peak pressure adjacent the nozzle orifice of approximately 3900-4300 psi within 5 milliseconds, while spacing the nozzle orifice off the skin by approximately 0.76 to 1.0 inches using an intradermal adapter with an internal diameter of approximately 0.5 to 0.70 inch, thus penetrating the skin tissue;

gradually and continuously reducing the pressure within the range of approximately 2300-3800 psi, during a substantial portion of which reduction the pressure decreases in a substantially linear manner, thereby distributing the entire volume of the liquid injectable over a large area in the intradermal space, causing local tissue disruption within the intradermal space, thereby encouraging an immune response; and

at the end of the injection, abruptly terminating the ampule pressure within 10 milliseconds, thus ensuring that the entire volume is delivered to the desired depth and avoiding any injectate leaking back through the tissue.

3. The method of claim 2, wherein the pressure of the liquid injectable at any point after the initial peak pressure is achieved, does not change more than 1000 psi in 1 millisecond or less.

4. The method of claim 2, wherein, the pressure of the liquid injectable has no more than one drop in pressure greater than 500 psi in less than 2 milliseconds during the first 10 milliseconds of the injection.

5. The method of claim 2, wherein the peak pressure is about 3900-4300 psi, the reduced pressure ranges between about 2300-3800 psi, and the pressure cut-off occurs within about 10 milliseconds.

6. The method of claim 2, wherein the volume of liquid injectable is less than or equal to 0.3 ml.

7. The method of claim 2, wherein the intradermal adapter is generally cylindrical and the distal end of the adapter terminates in a flange extending radially outward from the adapter and wherein the outer diameter of the said flange is at least about 0.2 inches greater than the inner diameter.

8. The method of claim 2, wherein the intradermal adaptor includes an abutment that fixes the nozzle orifice at a single, specific distance of between approximately 0.76-1.0 inch from the skin of the patient.

9. The method of claim 2, wherein the liquid injectable is DNA-based.

10. A method for performing intradermal injection of liquid injectables into humans, comprising:

fitting, adjacent an injection orifice of a needle-free injector, the proximal end of a substantially cylindrical intradermal adapter having a proximal and distal end and an internal abutment against which the injector is disposed to provide a fixed spacing of from approximately 0.76 to 1.0 inches from the injection orifice to the distal end of the adapter, the distal end having an inner diameter of from 0.50 to 0.70 inches;

selecting the needle-free injector having the injection orifice of from 0.004 to 0.005 inches;

holding the distal end of the intradermal adapter against the skin of the patient; and

using the needle-free injector to inject a liquid injectable in a volume of 0.3 ml or less into the intradermal region at an initial peak pressure of from 3900 to 4300 psi, and then permitting the injection pressure to decay to a level of about 2300 to 3800 psi, after which time the pressure is abruptly cut off, terminating the injection;

wherein the pressure of the liquid injectable continuously declines within the range between about 2300 and 3800 psi from the time immediately after the initial peak pressure is achieved until the injection ends abruptly.

11. The method of claim 10, wherein pressure decreases substantially linearly for a substantial portion of the pressure decline occurring after the initial peak pressure is achieved and prior to termination of the injection.

12. The method of claim 10 or claim 2, wherein pressure decreases substantially linearly for the latter half of the pressure decline occurring after the initial peak pressure is achieved and prior to termination of the injection.

13. The method of claim 10 or claim 2, wherein pressure decreases in a substantially linear manner from about 0.05 second after the initial pressure is achieved until the injection terminates abruptly.

14. A method for performing intradermal injection of liquid injectables into humans, comprising:

fitting, adjacent an injection orifice of a needle-free injector, the proximal end of a substantially cylindrical intradermal adapter having a proximal and distal end and an internal abutment against which the injector is disposed to provide a fixed spacing of from approximately 0.76 to 1.0 inches from the injection orifice to the distal end of the adapter, the distal end having an inner diameter of from 0.50 to 0.70 inches;

selecting the needle-free injector having the injection orifice of from 0.004 to 0.005 inches;

holding the distal end of the intradermal adapter against the skin of the patient; and

using the needle-free injector to inject a liquid injectable in a volume of 0.3 ml or less into the intradermal region at an initial peak pressure of from 3900 to 4300 psi, and then permitting the injection pressure to decay to a level of about 2300 to 3800 psi, after which time the pressure is abruptly cut off, terminating the injection;

wherein the injector injects the liquid injectable into the intradermal space, thereby depositing the medication over as large an area as possible and causing local tissue disruption within the intradermal space, which may activate an immune response.

15. A method for performing intradermal injection of liquid injectables into humans, comprising:

fitting, adjacent an injection orifice of a needle-free injector, the proximal end of a substantially cylindrical intradermal adapter having a proximal and distal end and an internal abutment against which the injector is disposed to provide a fixed spacing of from approximately 0.76 to 1.0 inches from the injection orifice to the distal end of the adapter, the distal end having an inner diameter of from 0.50 to 0.70 inches;

selecting the needle-free injector having the injection orifice of from 0.004 to 0.005 inches;

holding the distal end of the intradermal adapter against the skin of the patient; and

using the needle-free injector to inject a liquid injectable in a volume of 0.3 ml or less into the intradermal region at an initial peak pressure of from 3900 to 4300 psi, and then permitting the injection pressure to decay to a level of about 2300 to 3800 psi, after which time the pressure is abruptly cut off, terminating the injection;

wherein the pressure of the liquid injectable at any point after the initial peak pressure is achieved, does not change more than 1000 psi in 1 millisecond or less.

16. A method for performing intradermal injection of liquid injectables into humans, comprising:

fitting, adjacent an injection orifice of a needle-free injector, the proximal end of a substantially cylindrical intradermal adapter having a proximal and distal end and an internal abutment against which the injector is disposed to provide a fixed spacing of from approximately 0.76 to 1.0 inches from the injection orifice to the distal end of the adapter, the distal end having an inner diameter of from 0.50 to 0.70 inches;

selecting the needle-free injector having the injection orifice of from 0.004 to 0.005 inches;

holding the distal end of the intradermal adapter against the skin of the patient; and

using the needle-free injector to inject a liquid injectable in a volume of 0.3 ml or less into the intradermal region at an initial peak pressure of from 3900 to 4300 psi, and then permitting the injection pressure to decay to a level of about 2300 to 3800 psi, after which time the pressure is abruptly cut off, terminating the injection;

wherein, the pressure of the liquid injectable has no more than one drop in pressure greater than 500 psi in less than 2 milliseconds during the first 10 milliseconds of the injection.

17. A method for performing intradermal injection of liquid injectables into humans, comprising:

fitting, adjacent an injection orifice of a needle-free injector, the proximal end of a substantially cylindrical intradermal adapter having a proximal and distal end and an internal abutment against which the injector is disposed to provide a fixed spacing of from approximately 0.76 to 1.0 inches from the injection orifice to the distal end of the adapter, the distal end having an inner diameter of from 0.50 to 0.70 inches;

selecting the needle-free injector having the injection orifice of from 0.004 to 0.005 inches;

holding the distal end of the intradermal adapter against the skin of the patient; and

using the needle-free injector to inject a liquid injectable in a volume of 0.3 ml or less into the intradermal region at an initial peak pressure of from 3900 to 4300 psi, and then permitting the injection pressure to decay to a level of about 2300 to 3800 psi, after which time the pressure is abruptly cut off, terminating the injection;

wherein the peak pressure is about 3900-4300 psi, the reduced pressure ranges between about 2300-3800 psi, and the pressure cut-off occurs within about 10 milliseconds.

18. A method for performing intradermal injection of liquid injectables into humans, comprising:

fitting, adjacent an injection orifice of a needle-free injector, the proximal end of a substantially cylindrical intradermal adapter having a proximal and distal end and an internal abutment against which the injector is disposed to provide a fixed spacing of from approximately 0.76 to 1.0 inches from the injection orifice to the distal end of the adapter, the distal end having an inner diameter of from 0.50 to 0.70 inches;

selecting the needle-free injector having the injection orifice of from 0.004 to 0.005 inches;

holding the distal end of the intradermal adapter against the skin of the patient; and

using the needle-free injector to inject a liquid injectable in a volume of 0.3 ml or less into the intradermal region at an initial peak pressure of from 3900 to 4300 psi, and then permitting the injection pressure to decay to a level of about 2300 to 3800 psi, after which time the pressure is abruptly cut off, terminating the injection;

wherein the volume of liquid injectable is less than or equal to 0.3 ml.

19. A method for performing intradermal injection of liquid injectables into humans, comprising:

fitting, adjacent an injection orifice of a needle-free injector, the proximal end of a substantially cylindrical intradermal adapter having a proximal and distal end and an internal abutment against which the injector is disposed to provide a fixed spacing of from approximately 0.76 to 1.0 inches from the injection orifice to the distal end of the adapter, the distal end having an inner diameter of from 0.50 to 0.70 inches;

selecting the needle-free injector having the injection orifice of from 0.004 to 0.005 inches;

holding the distal end of the intradermal adapter against the skin of the patient; and

using the needle-free injector to inject a liquid injectable in a volume of 0.3 ml or less into the intradermal region at an initial peak pressure of from 3900 to 4300 psi, and then permitting the injection pressure to decay to a level of about 2300 to 3800 psi, after which time the pressure is abruptly cut off, terminating the injection;

wherein the intradermal adapter is generally cylindrical and the distal end of the adapter terminates in a flange extending radially outward from the adapter and wherein the outer diameter of the said flange is at least about 0.2 inches greater than the inner diameter.

20. A method for performing intradermal injection of liquid injectables into humans, comprising:

fitting, adjacent an injection orifice of a needle-free injector, the proximal end of a substantially cylindrical intradermal adapter having a proximal and distal end and an internal abutment against which the injector is disposed to provide a fixed spacing of from approximately 0.76 to 1.0 inches from the injection orifice to the distal end of the adapter, the distal end having an inner diameter of from 0.50 to 0.70 inches;

selecting the needle-free injector having the injection orifice of from 0.004 to 0.005 inches;

holding the distal end of the intradermal adapter against the skin of the patient; and

using the needle-free injector to inject a liquid injectable in a volume of 0.3 ml or less into the intradermal region at an initial peak pressure of from 3900 to 4300 psi, and then permitting the injection pressure to decay to a level of about 2300 to 3800 psi, after which time the pressure is abruptly cut off, terminating the injection;

wherein the liquid injectable is DNA-based.