Injection needle and device

• US 9,457,183 B2
• Filed: 06/13/2012
• Issued: 10/04/2016
• Est. Priority Date: 06/15/2011
• Status: Expired due to Fees

• Current Assignee: TRIPEP AB (Fastilium Property Group AB)
• Original Assignee: TRIPEP AB (Fastilium Property Group AB)
• Inventors: Sallberg, Matti, Frelin, Lars
• Primary Examiner(s): Stigell, Theodore
• Assistant Examiner(s): STILES, AMBER R.
• Application Number:
  US14/125,905
• Publication Number:
  US 20140121587A1
• Time in Patent Office: 1,574 Days
• Field of Search: 604 20- 21, 604/27, 604/173, 604/187, 604/191, 604/501, 435/173.6
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 39/29 Hepatitis virus
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61M 5/3291 Shafts with additional lateral openings
• CPC Class Codes: A61M 5/3298 Needles arranged in parallel
• CPC Class Codes: A61M 5/46 having means for controlling depth of insertion
• CPC Class Codes: A61N 1/0502 Skin piercing electrodes
• CPC Class Codes: A61N 1/306 Arrangements where at least part of the apparatus is introduced into the body
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: C12M 35/02 Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
• CPC Class Codes: C12N 2730/10134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2770/24234 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

Several needle assemblies and intracellular delivery devices that are used for the delivery of prophylactic and/or therapeutic material (i.e., delivered agents) into a tissue of a subject are disclosed. Preferably, the needle assemblies and/or the intracellular delivery devices comprise needles and/or needle electrodes, which are disposed in an array (e.g., a Y-type array having three outer needles and a center needle), wherein each needle in the array has a closed end and a plurality of apertures along each needle barrel, and the apertures on the needle barrels of the outer needles of the array are positioned to deliver the delivered agent toward the apertures of the center needle and/or an adjacent needle, but not outside of the active zone defined by the area within the needle array and the apertures on the needle barrel of the center needle are positioned to deliver the delivered agent toward the outer needles.

Claims

1. An apparatus for intracellular delivery of a delivered agent comprising:

a hub comprising at least one electrical connector;

a plurality of needles connected to the hub, wherein each needle of the plurality of needles comprises;

a closed end;

a needle barrel; and

a plurality of apertures that are disposed on the needle barrel;

an electrode; and

an electrical power supply configured to generate an electric field at the electrode, wherein the electrical power supply is connected to the electrode through the at least one electrical connector, wherein the plurality of needles is arranged in an array of four needles arranged in a Y-type pattern comprising a center needle and three outer needles disposed around the center needle, wherein the center needle is a needle-electrode configured to apply a first polarity voltage, and the three outer needles are needle-electrodes, configured to apply a second polarity voltage; and

wherein the center needle comprises apertures along the needle barrel, which are configured to direct delivery of the delivered agent toward apertures that are present on each of the three outer needles and each of the three outer needles comprises apertures along the needle barrel, which are configured to direct delivery of a delivered agent toward apertures that are present on the center needle so as to generate an opposing direction of delivery of the delivered agent.

2. The intracellular delivery apparatus of claim 1, wherein said needle-electrodes, are electrically connected to the electrical power supply and are configured to generate an electric field.

4. The intracellular delivery apparatus of claim 1, wherein the hub is a pocket hub, comprising an individual reservoir of a delivered agent for each needle or needle electrode.

5. The intracellular delivery apparatus of claim 1, wherein the hub comprises a single reservoir of a delivered agent for each needle or needle-electrode.

6. The intracellular delivery apparatus of claim 1, wherein at least one needle of the plurality of needles is at least partially laminated with an electrically non-conductive material.

7. The intracellular delivery apparatus of claim 1, further comprising an electrical power supply controller configured to control generation of the electric field.

8. The intracellular delivery apparatus of claim 7, wherein controlling generation of the electric field comprises controlling one or more of a pulse voltage, polarity of the needle-electrodes, a number of pulses, a pulse pattern, or a pulse duration.

10. The intracellular delivery apparatus of claim 1, wherein the electric field applied at the electrode and/or needle electrodes is commutating.

13. A method of nucleic acid immunization comprising:

providing the intracellular delivery apparatus of claim 1;

providing a voltage source;

inserting a plurality of needles and a plurality of electrodes or a plurality of

needle-electrodes of the intracellular delivery apparatus into a tissue of a subject;

displacing a nucleic acid through the plurality of apertures on the plurality of needles or the plurality of needle-electrodes and into the tissue of the subject; and

applying an electric field to the tissue of the subject.

14. The method of claim 13, wherein the nucleic acid immunization comprises introduction of a polynucleotide encoding a hepatitis antigen.

15. The method of claim 14, wherein the hepatitis antigen is a hepatitis C virus (HCV) antigen.

16. The method of claim 15, wherein the HCV antigen comprises NS3.

3. An intracellular delivery apparatus comprising:

a hub comprising at least one electrical connector;

a plurality of needles connected to the hub, wherein each needle of the plurality of needles comprises;

a closed end;

a needle barrel; and

a plurality of apertures that are disposed on the needle barrel;

an electrode; and

an electrical power supply configured to generate an electric field at the electrode, wherein the electrical power supply is connected to the electrode through the at least one electrical connector, wherein apertures on at least one needle barrel oppose the apertures on at least one other needle barrel wherein the plurality of needles is arranged in an array comprising a center needle and a plurality of outer needles disposed around the center needle, wherein the center needle comprises apertures along the needle barrel, which are configured to direct delivery of the delivered agent toward the outer needles and the outer needles comprise apertures along the needle barrel which are configured to direct delivery of a delivered agent toward the center needle so as to generate an opposing direction of delivery of the delivered agent;

a syringe in fluid communication with the hub; and

a delivery unit comprising;

a channel configured to receive the hub and the syringe;

a collar operable to fasten the syringe within the channel;

a handle, which operates to enclose the syringe and hub within the channel such that the closed ends of the needle barrels protrude from the channel and are available to engage a subject;

a charging element configured to be charged by the operation of the handle, the charging element coupled to a trigger and the syringe such that operation of the trigger releases the charging element and the charging element acts on the syringe, thereby displacing prophylactic and/or therapeutic material out of the syringe; and

an electrical port configured to mate with the electrical connector on the hub of the intracellular delivery apparatus thereby establishing electrical contact between the electrical power supply and the electrodes and/or needle-electrodes.

9. The intracellular delivery apparatus of claim 3, wherein the charging element is a spring configured to be compressed by the operation of the handle and configured to decompress upon operation of the trigger or when activated by an electrically operated transducer.

11. The intracellular delivery apparatus of claim 3, wherein the delivery unit is configured to control injection speed.

12. The intracellular delivery apparatus of claim 3, wherein the delivery unit is configured to control injection pressure.

17. A method of nucleic acid immunization comprising:

providing the intracellular delivery apparatus of claim 3;

providing a voltage source;

inserting a plurality of needles and a plurality of electrodes or a plurality of needle-electrodes of the intracellular delivery apparatus into a tissue of a subject;

displacing a nucleic acid through the plurality of apertures on the plurality of needles or the plurality of needle-electrodes and into the tissue of the subject; and

applying an electric field to the tissue of the subject.