Needleless syringe for the delivery of therapeutic agents

• US 7,320,677 B2
• Filed: 10/19/2001
• Issued: 01/22/2008
• Est. Priority Date: 10/20/2000
• Status: Expired due to Term

• Current Assignee: Socpra Sciences Et Gnie S.E.C.
• Original Assignee: Societe De Commercialisation Des Produits De La Recherche Appliquee - Socpra Sciences Et Genie, S.E.C.
• Inventors: Brouillette, Martin
• Primary Examiner(s): Sirmons; Kevin C.
• Assistant Examiner(s): GILBERT, ANDREW M
• Application Number:
  US10/398,855
• Publication Number:
  US 20040024350A1
• Time in Patent Office: 2,286 Days
• Field of Search: 604 68- 72, 604/48, 604/131, 604/140, 604/142, 604/147
• US Class Current: 604/68
• 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 5/2053 Media being expelled from injector by pressurised fluid or vacuum for infusion A61M5/145, A61M5/155
• CPC Class Codes: A61M 5/3015 for injecting a dose of particles in form of powdered drug, e.g. mounted on a rupturable membrane and accelerated by a gaseous shock wave or supersonic gas flow cell injection devices C12M3/006

Abstract

A needleless syringe for subcutaneously delivering a therapeutic agent comprising a generally constant diameter elongate tubular nozzle and an inert gas reservoir thereto is described herein. The reservoir is advantageously mounted to the upstream end of the tubular nozzle through a contraction that is either gradual or sudden and wherein a membrane is positioned between the reservoir and the therapeutic agent.

Claims

1. A needleless syringe for delivering therapeutic particles to a skin surface, comprising:

a gas reservoir for receiving a gas at a first pressure, the gas reservoir having a first internal diameter and an opening;

an elongate tubular nozzle having an upstream end mounted to the opening of the gas reservoir, an upstream portion and a downstream end;

an arrangement comprising;

the elongate tubular nozzle having a generally constant second internal diameter smaller than the first internal diameter and being at a second internal a pressure;

a contraction of the gas reservoir from the first internal diameter to the second internal diameter;

a source of therapeutic particles positioned in the upstream end of the elongated tubular nozzle of generally constant second internal diameter; and

a partition for separating the gas reservoir from the source of particles, the partition being designed to be opened and to withstand large pressure differences between the gas reservoir and the elongate tubular nozzle; and

wherein the first and second internal diameters and the first and second gas pressures define respective, predetermined diameter and pressure ratios adapted to produce, in response to opening of the partition, a gaseous expansion generating a) a stationary expansion wave in the contraction leading to a sonic flow at the upstream end of the tubular nozzle and b) non-stationary expansion waves traveling downstream in the elongate tubular nozzle to carry the therapeutic particles into a supersonic gas flow and deliver the therapeutic particles to the skin surface through the downstream end of the tubular nozzle.

2. A needleless syringe as recited in claim 1, wherein said opening of said partition further generates an unsteady expansion traveling upstream into said reservoir.

3. A needleless syringe as recited in claim 2, wherein said opening of said partition further generates a shock wave in said elongate tubular nozzle.

4. A needleless syringe as recited in claim 1, wherein said reservoir is pre-loaded with pressurized gas.

5. A needleless syringe as recited in claim 1, wherein a pattern of stationary and non-stationary expansion waves is generated at said downstream end of said elongate tubular nozzle when said gaseous expansion and said particles reach the exit of said elongate tubular nozzle.

6. A needleless syringe as recited in claim 1, wherein the particles exit said downstream end of said tubular nozzle with respective velocities having an essentially spatially uniform and parallel distribution.

7. A needleless syringe as recited in claim 1, further comprising i) a gas reserve mounted at an upstream end of said gas reservoir and containing a source of pressurized gas, and ii) a release valve separating said pressurized gas source from said gas reservoir, said gas reservoir being at essentially atmospheric pressure;

whereby the opening of said release valve allows the pressurized gas to fill said gas reservoir until said partition ruptures generating a) said stationary expansion wave in said contraction leading to the sonic flow at the upstream end of the tubular nozzle and b) said non-stationary expansion waves traveling downstream in said elongate tubular nozzle, accelerating the particles towards said downstream end of said tubular nozzle.

8. A needleless syringe as recited in claim 7, wherein said release valve includes a small diameter orifice controlling the flow rate of said pressurized gas into said reservoir upon opening of said release valve.

9. A needleless syringe as recited in claim 8, wherein said downstream end of said tubular nozzle is enlarged to form a spacer between said downstream end and a target plane, said spacer being so shaped as to create a substantially normal wave near the surface of the target plane.

10. A needleless syringe as recited in claim 9, wherein said substantially normal wave decelerates the particles, generating a radially uniform particle velocity distribution.

11. A needleless syringe as recited in claim 1, further comprising a silencer mounted to the downstream end of said tubular nozzle.

12. A needleless syringe as recited in claim 1, wherein said gas reservoir further comprises:

a compressed gas reserve;

a first chamber filled with a gas substantially at atmospheric pressure and a second chamber filled with a gas at atmospheric pressure;

a piston separating said first chamber from said second chamber;

a release valve separating said compressed gas reserve from said first chamber;

a membrane forming said partition and separating the gas of said second chamber from said tubular nozzle;

whereby opening said release valve allows the compressed gas from the reserve to fill said first chamber pushing said piston into said second chamber, compressing the gas into said second chamber until said membrane ruptures, generating a) said stationary expansion wave in said contraction leading to the sonic flow at the upstream end of the tubular nozzle and b) said non-stationary expansion waves traveling downstream in said elongate tubular nozzle, accelerating the particles towards said downstream end of said nozzle.

13. A needleless syringe as recited in claim 12, wherein said piston has an inertia capable of compressing said compressed gas reserve to several times the pressure of said compressed gas.

14. A needleless syringe as recited in claim 1, wherein said reservoir further comprises:

a downstream chamber filled with a gas at substantially atmospheric pressure and an upstream chamber;

a piston attached to a compressed spring and separating said upstream chamber and said downstream chamber;

a membrane forming said partition and separating the gas of said upstream chamber from said tubular nozzle;

whereby releasing said compressed spring pushes said piston into said upstream chamber thereby compressing the gas in said upstream chamber causing said membrane to rupture, generating a) said stationary expansion wave in said contraction leading to the sonic flow at the upstream end of the tubular nozzle and b) said non-stationary expansion waves traveling downstream in said elongate tubular nozzle, accelerating the particles towards said downstream end of said nozzle.

15. A needleless syringe as recited in claim 14, wherein said piston has an inertia capable of compressing said compressed gas reserve to several times the pressure of said compressed gas.

16. A needleless syringe as defined in claim 1, wherein the second internal pressure of the elongate tubular nozzle is initially lower than the atmospheric pressure.

17. A needleless syringe as defined in claim 1, wherein the ratio of the first internal diameter to the second internal diameter is about 3.2.

18. A needleless syringe as defined in claim 1, wherein the ratio of the first internal diameter to the second internal diameter is about 3.75.

19. A needleless syringe as defined in claim 1, wherein the ratio of the first internal diameter to the second internal diameter is equal to or larger than 3.2.

20. A needleless syringe as defined in claim 1, wherein the gas received in the gas reservoir is an inert gas and wherein the ratio of the first gas pressure to the second gas pressure is situated between about 20 and about 80.

21. A needleless syringe as defined in claim 20, wherein the inert gas comprises helium.

22. A needleless syringe as defined in claim 1, wherein the ratio of the first internal diameter to the second internal diameter is equal to or larger than 3.2, wherein the gas received in the gas reservoir is an inert gas and wherein the ratio of the first gas pressure to the second gas pressure is situated between about 20 and about 80.

23. A needleless syringe as defined in claim 1, wherein the second internal diameter of the tubular nozzle is 4 mm.

24. A needleless syringe as defined in claim 1, wherein the second internal diameter of the tubular nozzle is 4.9 mm.

25. A needleless syringe as defined in claim 1, wherein the second internal diameter of the tubular nozzle is equal to or larger than 4 mm.

26. A needleless syringe as defined in claim 1, wherein the tubular nozzle has a length and wherein a ratio of the length of the tubular nozzle to the constant second internal diameter of the nozzle is 12.5.

27. A method for delivering therapeutic particles to a skin surface, comprising:

providing a gas reservoir for receiving a gas at a first pressure, the gas reservoir having a first internal diameter and an opening;

mounting an upstream end of an elongate tubular nozzle to the opening of the gas reservoir, the elongate tubular nozzle also comprising an upstream portion and a downstream end;

forming the elongate tubular nozzle with a generally constant second internal diameter smaller than the first internal diameter, the elongate tubular nozzle being at a second internal gas pressure;

contracting the gas reservoir from the first internal diameter to the second internal diameter;

placing a source of therapeutic particles in the upstream end of the elongated tubular nozzle having a generally constant second internal diameter;

separating the gas reservoir from the source of particles by means of a partition designed to be opened and to withstand large pressure differences between the gas reservoir and the elongate tubular nozzle; and

providing a predetermined diameter ratio of the first internal diameter to the second internal diameter and a predetermined pressure ratio of the first gas pressure to the second gas pressure to produce, in response to opening of the partition, a gaseous expansion generating a) a stationary expansion wave in the contraction leading to a sonic flow at the upstream end of the tubular nozzle and b) non-stationary expansion waves traveling downstream in the elongate tubular nozzle to carry the therapeutic particles into a supersonic gas flow and deliver the therapeutic particles to the skin surface through the downstream end of the tubular nozzle.

28. A method as recited in claim 27, further including:

providing a gas reserve containing a source of pressurized gas, the gas reservoir being at substantially atmospheric pressure; and

providing a release valve, wherein said gas reserve is mounted to an upstream end of said gas reservoir and wherein said release valve separates said pressurized gas from said gas reservoir;

wherein generating a) said stationary expansion wave in said contraction leading to a sonic flow at the upstream end of the tubular nozzle and b) said non-stationary expansion waves traveling downstream in said elongate tubular nozzle comprises opening the release valve to allow the pressurized gas to fill the gas reservoir until the partition opens to thereby accelerate the particles towards the downstream end of the nozzle.

29. A method as recited in claim 27, comprising producing, at the downstream end of the tubular nozzle, an essentially spatially uniform and parallel particle velocity distribution.

30. A method as recited in claim 27, wherein the opening of the partition produces an unsteady expansion traveling upstream into said gas reservoir, and wherein said unsteady expansion travels in a downstream direction after reflecting from an upstream end of the gas reservoir.

31. A method as recited in claim 30, comprising producing an essentially constant high velocity flow that terminates when the leading front of said reflected unsteady expansion reaches the downstream end of the nozzle.

32. A method as recited in claim 27, comprising controlling the velocity of the particles impacting a target surface by selecting a) initial and physical properties of the gases comprised in the gas reservoir and said nozzle and b) the ratio of said first internal diameter to said second internal diameter and c) the ratio of the first gas pressure to the second gas pressure.

33. A method as recited in claim 27 wherein providing a gas reservoir includes:

providing a first chamber filled with a first pressurized gas;

providing a second chamber downstream from the first chamber and including a closed orifice that may be opened to the atmosphere, the second chamber being filled with a second gas at a lower pressure relative to the first gas;

providing a first membrane separating the first chamber from the second chamber;

providing a second membrane separating the second chamber from the tubular nozzle;

wherein producing non-stationary expansion waves comprises opening the orifice to cause a pressure-drop in the second chamber resulting in the rupturing of said first membrane whereby the first pressurized gas fills the second chamber in turn rupturing said second membrane, generating a) said stationary expansion wave in said contraction leading to the sonic flow at the upstream end of the tubular nozzle and b) said non-stationary expansion waves traveling downstream in said elongate tubular nozzle, accelerating the particles towards the downstream end of the nozzle.

34. A method as recited in claim 27, wherein providing a gas reservoir includes:

providing a compressed gas reserve;

providing a first chamber filled with a gas at atmospheric pressure and a second chamber filled with a gas at atmospheric pressure;

providing a piston separating the first chamber from the second chamber;

providing a release valve separating the compressed gas reserve from the first chamber;

providing a membrane forming the partition and separating the gas of the second chamber from the tubular nozzle;

wherein generating a) said stationary expansion wave in said contraction leading to a sonic flow at the upstream end of the tubular nozzle and b) said non-stationary expansion waves traveling downstream in said elongate tubular nozzle comprises opening the release valve to allow the compressed gas to fill the first chamber pushing the piston into the second chamber, compressing the gas in the second chamber until the membrane ruptures, generating a) said stationary expansion wave in said contraction leading to the sonic flow at the upstream end of the tubular nozzle and b) said non-stationary expansion waves traveling downstream in said elongate tubular nozzle, accelerating the particles towards the downstream end of the nozzle.

35. A method as recited in claim 34, further comprising compressing said compressed gas reserve to several times the pressure of said compressed gas by means of the inertia of said piston.

36. A method as recited in claim 27, wherein providing a gas reservoir includes:

providing a downstream chamber filled with a gas at substantially atmospheric pressure and an upstream chamber;

providing a piston attached to a compressed spring and separating the upstream chamber and the downstream chamber; and

providing a membrane forming a partition and separating the gas of the downstream chamber from the tubular nozzle;

wherein generating a) said stationary expansion wave in said contraction leading to a sonic flow at the upstream end of the tubular nozzle and b) said non-stationary expansion waves traveling downstream in said elongate tubular nozzle comprises releasing the compressed spring to push the piston into the downstream chamber thereby compressing the gas in the downstream chamber causing the membrane to rupture, generating a) said stationary expansion wave in said contraction leading to the sonic flow at the upstream end of the tubular nozzle and b) said non-stationary expansion waves traveling downstream in said elongate tubular nozzle, accelerating the particles towards the downstream end of the nozzle.

37. A method as recited in claim 36, further comprising compressing said compressed gas reserve to several times the pressure of said compressed gas by means of the inertia of said piston.

38. A method for delivering therapeutic particles as defined in claim 27, wherein the second internal gas pressure of the elongate tubular nozzle is initially lower than atmospheric pressure.

39. A method for delivering therapeutic particles as defined in claim 27, wherein the ratio of the first internal diameter to the second internal diameter is about 3.2.

40. A method for delivering therapeutic particles as defined in claim 27, wherein the ratio of the first internal diameter to the second internal diameter is about 3.75.

41. A method for delivering therapeutic particles as defined in claim 27, wherein the ratio of the first internal diameter to the second internal diameter is equal to or larger than 3.2.

42. A method for delivering therapeutic particles as defined in claim 27, wherein the gas received in the gas reservoir is an inert gas and wherein the ratio of the first gas pressure to the second gas pressure is situated between about 20 and about 80.

43. A method for delivering therapeutic particles as defined in claim 42, wherein the inert gas comprises helium.

44. A method for delivering therapeutic particles as defined in claim 27, wherein the ratio of the first internal diameter to the second internal diameter is equal to or larger than 3.2, wherein the gas received in the gas reservoir is an inert gas and wherein the ratio of the first gas pressure to the second gas pressure is situated between about 20 and about 80.

45. A method for delivering therapeutic particles as defined in claim 27, wherein the second internal diameter of the tubular nozzle is 4 mm.

46. A method for delivering therapeutic particles as defined in claim 27, wherein the second internal diameter of the tubular nozzle is 4.9 mm.

47. A method for delivering therapeutic particles as defined in claim 27, wherein the second internal diameter of the tubular nozzle is equal to or larger than 4 mm.

48. A method for delivering therapeutic particles as defined in claim 27, wherein the tubular nozzle has a length and wherein a ratio of the length of the tubular nozzle to the constant second internal diameter of the nozzle is 12.5.

49. A needleless syringe, for delivering therapeutic particles to a skin surface, comprising:

a gas reservoir having a first internal diameter and an opening;

an elongate tubular nozzle having an upstream end mounted to the opening of the gas reservoir and a downstream end;

an arrangement for producing non-stationary expansion waves traveling downstream in the elongate tubular nozzle and for carrying by means of the non-stationary expansion waves the therapeutic particles at a velocity sufficient to deliver the therapeutic particles to the skin surface, the arrangement comprising;

the elongate tubular nozzle having a generally constant second internal diameter;

a contraction of the gas reservoir from the first diameter to the second diameter;

an upstream portion of the elongated tubular nozzle of generally constant second internal diameter for accommodating a source of therapeutic particles;

a rupturable partition for separating the gas reservoir from the source of particles, the partition being designed to withstand large pressure differences between the gas reservoir and the elongate tubular nozzle; and

a ratio of the first internal diameter to the second internal diameter which is sufficient to allow the contraction of the gas reservoir to produce, in response to a rupture of the partition caused by a difference of gas pressure between the gas reservoir and the elongate tubular nozzle, a gaseous expansion generating a) a stationary expansion wave in the contraction leading to a sonic flow at the upstream end of the tubular nozzle and b) the non-stationary expansion waves traveling downstream in the elongate tubular nozzle to carry the therapeutic particles into a supersonic gas flow;

wherein said gas reservoir further comprises;

a first chamber filled with a first pressurized gas;

a second chamber mounted downstream from said first chamber and including a closed orifice that may be opened to the atmosphere, said second chamber being filled with a second gas at a lower pressure relative to the first gas;

a first membrane separating said first chamber from said second chamber;

a second membrane separating said second chamber from said tubular nozzle;

whereby opening said orifice to the atmosphere results in a pressure-drop in said second chamber resulting in a rupture of said first membrane whereby the first pressurized gas fills the second chamber in turn rupturing said second membrane, generating a) said stationary expansion wave in said contraction leading to a sonic flow at the upstream end of the tubular nozzle and b) said non-stationary expansion waves traveling downstream in said elongate tubular nozzle, accelerating the particles into a supersonic gas flow towards said downstream and of said nozzle.

50. A needleless syringe for delivering particles, said syringe comprising:

a first reservoir having a first internal diameter, said reservoir having an opening defining a contraction;

an elongate tubular nozzle having an upstream end and a downstream end;

said elongate tubular nozzle having a generally constant second internal diameter;

a second reservoir interposed between the opening of said first reservoir and said tubular nozzle, said second reservoir having substantially said second internal diameter;

a first partition separating said first reservoir from said second reservoir;

a second partition separating said second reservoir from said tubular nozzle;

whereby positively pressurizing with a gas said first reservoir relative to said second reservoir results in rupturing said first partition whereby said gas fills the second reservoir in turn rupturing said second partition, generating a) a stationary expansion wave in said contraction leading to a sonic flow at the upstream end of the tubular nozzle and b) non-stationary expansion waves traveling downstream in said elongate tubular nozzle, accelerating the particles into a supersonic gas flow towards said downstream end of said nozzle;

wherein said first reservoir is filled with a positively pressurized gas relative to the atmospheric pressure, and wherein said second reservoir further comprises a closed orifice that may be opened to the atmosphere for causing said positive pressurizing of said first reservoir relative to said second reservoir.

51. A method for delivering particles comprising:

providing a first reservoir having a first internal diameter;

the reservoir having an opening defining a contraction;

providing an elongate tubular nozzle having an upstream end and a downstream end;

the elongate tubular nozzle having a generally constant second internal diameter;

interposing a second reservoir between the opening of said first reservoir and said tubular nozzle, said second reservoir having substantially said second internal diameter;

separating said first reservoir from said second reservoir with a first partition;

separating said second reservoir from said tubular nozzle with a second partition; and

positively pressurizing with a gas said first reservoir relative to said second reservoir to rupture said first partition whereby said gas fills the second reservoir in turn rupturing said second partition, generating a) a stationary expansion wave in said contraction leading to a sonic flow at the upstream end of the tubular nozzle and b) non-stationary expansion waves traveling downstream in said elongate tubular nozzle, accelerating the particles into a supersonic gas flow towards said downstream end of said nozzle;

wherein said method further comprises filling said first reservoir with a positively pressurized gas relative to the atmospheric pressure, and providing in said second reservoir a closed orifice and opening said orifice to the atmosphere for causing said positive pressurizing of said first reservoir relative to said second reservoir.