Method for in vivo delivery of therapeutic agents

• US 6,978,172 B2
• Filed: 12/30/2002
• Issued: 12/20/2005
• Est. Priority Date: 11/05/1997
• Status: Expired due to Fees

• Current Assignee: Hisamitsu Pharmaceutical Company Incorporated
• Original Assignee: Hisamitsu Pharmaceutical Company Incorporated
• Inventors: Mori, Kenji, Sato, Shuji, Nozawa, Iwao
• Primary Examiner(s): Thanh, LoAn H.
• Application Number:
  US10/335,641
• Publication Number:
  US 20030097090A1
• Time in Patent Office: 1,086 Days
• Field of Search: 604 20- 21, 604/96.01, 435/285.2, 435/173.6
• US Class Current: 604/20
• CPC Class Codes: A61N 1/042 Material of the electrode
• CPC Class Codes: A61N 1/0424 Shape of the electrode
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/0444 Membrane
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

Electroporation electrodes are laminated to a permeable membrane to form an electrode membrane. Such an electrode membrane is useful for a continuous controlled delivery of a therapeutic agent through the skin or mucosa, when placed in direct contact with the skin or mucosa and by application of electric field pulses at specified intervals. An electrode membrane can be assembled such that it incorporates an iontophoretic electrode in the same device. This device can be jointly utilized for electroporation and iontophoretic drug delivery through the skin and mucosal membrane.

Claims

1. A method of in vivo administration of a therapeutic agent including the following steps:

(a) contacting a device which includes an agent permeable membrane having a pair of contact electrodes to a site of administration such that the agent permeable membrane directly contacts the site of administration, a casing attached to the agent permeable membrane forming a reservoir, a pharmaceutical composition including the therapeutic agent where the pharmaceutical composition is contained in the reservoir, an iontophoretic electrode which is located in the reservoir;

(b) contacting a counter electrode to a second site;

(c) applying a first electric signal to the contact electrodes; and

(d) applying a second electric signal to the iontophoretic electrode.

2. The method of claim 1 where the second electric signal is a pulsed current signal from about 0.01 to 10 mA.

3. The method of claim 2 where the pulsed current signal is from about 0.01 to 5 mA.

4. The method of claim 1 where the second electric signal creates a voltage differential from about 0.1 to 50 V between the iontophoretic electrode and the counter electrode.

5. The method of claim 4 where the voltage differential is from about 1 to 30 V.

6. The method of claim 5 where the voltage differential is from about 3 to 15 V.

7. The method of claim 1 where the second electric signal is a pulse depolarization signal at a pulse frequency from about 100 Hz to 1000 KHz.

8. The method of claim 7 where the pulse frequency is from about 1 to 500 KHz.

9. The method of claim 8 where the pulse frequency is from about 10 KHz to 300 KHz.

10. The method of claim 1 where the second electric signal has a duty cycle with an ON/OFF ratio between about 1 and 99%.

11. The method of claim 10 where the duty cycle is between about 10 and 80%.

12. The method of claim 11 where the duty cycle is between about 15 and 50%.