Methods and devices for desmopressin drug delivery

• US 8,399,410 B2
• Filed: 08/06/2008
• Issued: 03/19/2013
• Est. Priority Date: 08/06/2007
• Status: Expired due to Fees

• Current Assignee: Serenity Pharmaceuticals Corporation
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Herschkowitz, Samuel, Fein, Seymour
• Primary Examiner(s): Russel, Jeffrey E
• Application Number:
  US12/186,886
• Publication Number:
  US 20090042970A1
• Time in Patent Office: 1,686 Days
• Field of Search: None
• US Class Current: 514/10.9
• CPC Class Codes: A61K 38/095 Oxytocins; Vasopressins; Related peptides
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• CPC Class Codes: A61M 5/168 Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body flow control in general G05D7/00
• CPC Class Codes: A61M 5/482 Varying injection pressure, e.g. by varying speed of injection
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 7/12 Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10

Abstract

Disclosed are devices for urine voiding postponement, and methods for treating conditions such as central diabetes insipidus, enuresis, nocturia, urinary frequency or incontinence. The devices deliver a desmopressin flux through the skin of a patient in a low dose amount just necessary to achieve a desired anti-diuretic effect without undesirable side effects such as hyponatremia. The devices are designed to permit a state of normal urinary production to return quickly after the desmopressin flux is terminated.

Claims

1. A method of modulating urine production in a patient in need of such modulation comprising:

(a) administering desmopressin, to or across the skin of the patient, at a first flux rate sufficient to establish a desmopressin concentration in the blood within the range of about 0.5 to 2 pg/ml and insufficient to establish a desmopressin concentration in the blood greater than about 2 pg/ml, thereby reducing urine production in the patient;

(b) continuing to administer desmopressin at a second, lower flux rate sufficient to maintain the desmopressin concentration in the blood within the range for a period of time; and

(c) terminating administration of the desmopressin, thereby restoring urine production within about two hours of termination.

2. The method of claim 1, wherein the patient suffers from diabetes insipidus, enuresis, urinary frequency, nocturia or incontinence.

3. The method of claim 1, wherein the desmopressin is administered at a flux rate between about 5 and 35 ng/hour.

4. The method of claim 3, wherein the flux rate is between about 10 and 20 ng/hour.

5. The method of claim 3, wherein the flux rate is between about 5 and 15 ng/hour.

6. The method of claim 1, wherein the period of time of step b is at least two hours.

7. The method of claim 6, wherein the period of time of step b is four to seven hours.

8. The method of claim 1, wherein the desmopressin is administered with a delivery device applied to the skin of the patient.

9. The method of claim 8, wherein the delivery device comprises a solution flow control means, the method comprising actuating the control means to initiate a first, higher flux rate to establish a preselected desmopressin concentration within the blood of a patient and to initiate a second, lower flux rate to maintain the concentration, thereby to maintain a substantially constant predetermined desmopressin concentration in the blood of the patient.

10. The method of claim 8, wherein the administration is terminated by removing the delivery device from the skin of the patient.

11. The method of claim 8, wherein the delivery device comprises a desmopressin solution flow switch for initiating or terminating a flow of desmopressin to the patient.

12. A method of modulating urine production in a patient in need of such modulation comprising:

administering a sustained-release desmopressin composition to or across the skin of the patient, wherein the desmopressin is released at an initial flux rate sufficient to establish a desmopressin concentration in the blood within the range of about 0.5 to 2 pg/ml and thereafter at a lower flux rate to maintain the blood concentration within said range for a period of time and insufficient to establish a desmopressin concentration in the blood greater than about 2 pg/ml, thereby reducing urine production in the patient, and wherein the flux rate further decreases, after the period of time, to a level insufficient to maintain the desmopressin concentration in the blood, thereby restoring urine production within about two hours.

13. The method of claim 12, wherein the period of time is between about 2 and 8 hours.

14. The method of claim 13, wherein the period of time is between about 4 and 7 hours.

15. The method of claim 12, wherein the flux rate sufficient to establish or maintain the desmopressin concentration in the blood is between about 5 and 35 ng/hour.

16. The method of claim 12, wherein the patient suffers from diabetes insipidus, enuresis, urinary frequency, nocturia or incontinence.

17. The method of claim 12, wherein the administering of the sustained-release desmopressin composition comprises inserting into the skin one or more microstructures comprising desmopressin and a polymer from which the desmopressin is released at a controlled rate.

18. The method of claim 12, wherein the administering of the desmopressin composition comprises inserting into the skin one or more microneedles.