Method of administration of insulin

• US 5,672,581 A
• Filed: 10/28/1994
• Issued: 09/30/1997
• Est. Priority Date: 01/29/1993
• Status: Expired due to Term

• Current Assignee: Aradigm Corporation
• Original Assignee: Aradigm Corporation
• Inventors: Lloyd, Lester John, Rubsamen, Reid M.
• Primary Examiner(s): DAVENPORT, AVIS MICHELLE
• Application Number:
  US08/331,056
• Time in Patent Office: 1,068 Days
• Field of Search: 514/2, 514/3, 514/4, 424/489, 424/43, 424/145, 435/4, 435/810, 530/303, 128/200.14, 128/200.16, 128/200.23, 128/200.24, 128/203.12, 128/203.15
• US Class Current: 514/5.9
• CPC Class Codes: A61J 7/0418 with electronic history memory
• CPC Class Codes: A61J 7/0427 with direct interaction with a dispensing or delivery system
• CPC Class Codes: A61J 7/0445 for preventing drug dispensing during a predetermined time period
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• CPC Class Codes: A61M 11/001 Particle size control
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61M 15/0031 by bursting or breaking the package, i.e. without cutting or piercing
• CPC Class Codes: A61M 15/0051 the dosages being arranged on a tape, e.g. strips
• CPC Class Codes: A61M 15/0055 the used dosages being coiled
• CPC Class Codes: A61M 15/0066 with means for varying the dose size
• CPC Class Codes: A61M 15/008 Electronic counters
• CPC Class Codes: A61M 15/0085 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 15/009 using medicine packages with incorporated spraying means, e.g. aerosol cans pocket atomiser of the injector type A61M11/08
• CPC Class Codes: A61M 16/142 with semi-permeable walls separating the liquid from the respiratory gas
• CPC Class Codes: A61M 2016/0021 with a proportional output signal, e.g. from a thermistor
• CPC Class Codes: A61M 2202/062 Desiccants
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/8206 : battery-operated

Abstract

A method for treating a patient suffering from diabetes mellitus by delivering aerosolized insulin to the patient and a programmed, portable, hand-held device used in such treatment methodology is disclosed. Two basic types of drug delivery devices are disclosed for use in connection with the present invention. In accordance with the first type of device the insulin is contained within a low boiling point propellant which is held within a canister under pressure. In accordance with the second type of device the insulin is present within a container in solution and the solution is moved through a porous membrane to create an aerosolized formulation which is inhaled by the patient. In accordance with both devices a measured amount of insulin containing formulation is automatically released into the inspiratory flow path of a patient in response to information obtained from determining the inspiratory flow rate and inspiratory volume of a patient. The determination of values and release of drugs are carried out in real time. Reproducibly dosing of insulin to the patient is obtained by repeatedly providing for automatic release of insulin formulation at the same inspiratory flow rate and inspiratory volume. To maximize the efficiency of the delivery of the insulin formulation the formulation is released at an inspiratory flow rate in the range of from about 0.1 to about 2.0 liters/second and a measured inspiratory volume in the range of about 0.1 to about 0.8 liters.

Claims

1. A method of administering insulin to a human patient, comprising:

determining a drug release point based on real time values of both a patient'"'"'s inspiratory flow rate and inspiratory volume;

releasing an aerosolized formulation of insulin into the patient'"'"'s inspiratory flow path when the inspiratory flow rate is in the range of from about 0.10 to 2.0 liters/second and the patient'"'"'s inspiratory volume is in the range of from about 0.15 to about 0.80 liters.

2. The method of claim 1, wherein the inspiratory flow rate is in the range of from about 0.2 to about 1.8 liters/second and the inspiratory volume is in the range of from about 0.15 to about 0.40 liters.

3. The method of claim 1, wherein the inspiratory flow rate is in the range of from about 0.15 to about 1.8 liters/second and the inspiratory volume is in the range of from about 0.15 to about 0.25 liters, and wherein the insulin formulation is released at a velocity such that particles of insulin formulation are at zero velocity or reduce to zero velocity after traveling 2 cm or less from a point of release in the absence of the patient'"'"'s inspiration, and wherein the aerosolized insulin formulation has a particle size in the range of from about 0.5 to 12 microns.

4. The method of claim 1, wherein the determining and releasing are carried out during a single inhalation of the patient.

5. The method of claim 1 wherein the aerosolized insulin formulation is in the form of aerosolized particles of a solution.

6. The method of claim 5, wherein the solution is an aqueous solution.

7. The method of claim 1, wherein the aerosolized insulin formulation is in the form of aerosolized particles of a dry insulin powder.

8. The method of claim 1, wherein the determining is carried out by measuring via electronic air flow measurement components.

9. The method of claim 1, wherein the determining is carried out by measuring via mechanical air flow measurement components.

10. The method of claim 1, wherein the releasing is begun and completed while the inspiratory flow rate is in the range of from about 0.10 to about 2.0 liters/second and wherein the releasing is begun while the inspiratory volume is in the range of about 0.15 to about 0.40 liters.

11. The method of claim 1, further comprising:

repeating the determining and releasing a plurality of times.

12. The method of claim 1, further comprising:

monitoring serum glucose levels in the patient; and

repeating the determining, releasing and monitoring a plurality of times over a period of time so as to maintain a desired serum glucose level in the patient.

13. The method as claimed in claim 12, wherein the amount of insulin administered and the glucose level monitored are continually recorded and adjustments are made in the amount of insulin administered based on the effect of insulin administration on the glucose levels of the patient.

14. The method as claimed in claim 12, wherein the amount of insulin administered is in the range of 1 unit per day to 50 units per day and wherein the desired serum glucose level in the patient is within the range of 50 mg/dl to 300 mg/dl.

15. The method of claim 11, further comprising:

orally administering a sulfonylurea drug to the patient.

16. The method of claim 15, wherein the sulfonylurea drug is selected from the group consisting of acetohexamide, chlorpropamide, tolazamide, tolbutamide, glipzide and glyburide.

17. A method of treating diabetes mellitus, comprising:

repeatedly administering to a patient a predetermined amount of aerosolized insulin formulation wherein the aerosolized insulin formulation is administered at substantially the same inspiratory flow rate and inspiratory volume so as to repeatedly administer substantially the same amount of insulin formulation to patient at each administration.

18. The method of claim 17, wherein the insulin formulation is repeatedly administered at an inspiratory flow rate in the range of about 0.10 to about 2.0 liters/second and an inspiratory volume in the range of about 0.15 to about 0.80 liters.

19. The method of claim 17, wherein the inspiratory flow rate and inspiratory volume are within ±

10% at each repeated administration of insulin formulation.

20. A disposable insulin formulation package, comprising:

a first container having therein dry insulin the container comprising at least one wall which is collapsible by the application of a force causing a pressure of about 20 psi to 100 psi and further comprising a porous membrane with pores having a diameter of about 0.25 micron to about 6 microns; and

a second container having a flowable liquid therein connected to and in fluid connection with the first container, the fluid connection being interrupted by a membrane which is ruptured by the application of pressure of about 50 psi or less.