Method of administration of insulin

• US 5,364,838 A
• Filed: 01/29/1993
• Issued: 11/15/1994
• Est. Priority Date: 01/29/1993
• Status: Expired due to Term

• Current Assignee: Aradigm Corporation
• Original Assignee: Miris Medical Corporation
• Inventors: Rubsamen, Reid M.
• Primary Examiner(s): Lee, Lester L.
• Assistant Examiner(s): DAVENPORT, AVIS MICHELLE
• Application Number:
  US08/011,281
• Time in Patent Office: 655 Days
• Field of Search: 514/2, 514/3, 514/4
• 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 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• 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 and a programmed, portable, hand-held device and formulations used in such treatment methodology is disclosed. The programmed device is loaded with a container which includes a formulation comprised of insulin dispersed in a suitable propellant such as a low boiling point propellant. The container may be completely sealed and may be punctured on insertion in the device but preferably includes a single valve which can be opened to release insulin forced from the container by the propellant. A valve for releasing formulation is controlled by an electronic means for opening the valve in response to a measured threshold of airflow which airflow is measured by an airflow detection means positioned between the valve and a mouthpiece. Insulin is administered when the patient inspiratory flow exceeds a preset threshold. The airflow is measured and when a threshold amount of airflow is achieved, the valve opening means is actuated and a controlled amount of insulin is released from the container. The device includes a microprocessor connected to the means for measuring airflow and the means for opening the valve. The microprocessor is programmed to control the amount of insulin released, based on the particular needs of the patient. The device is electronically connectable to a device which measures serum glucose level and can adjust insulin release amounts based of measured glucose levels.

Claims

1. A method of intrapulmonary administration of insulin, comprising:

measuring the inspiratory flow of a patient and calculating a threshold level in an inhalation cycle at which release of drug is to take place, the threshold level being determined in a manner so as to maximize the repeatability of the amount of insulin delivered to the patient on releasing insulin;

releasing a metered dose of aerosolized insulin from a pressurized canister containing insulin in combination with a low boiling point propellant, the releasing being carried out upon reaching the threshold level generated by the patient inhaling;

inhaling the metered dose of aerosolized insulin into the lungs of a patient; and

monitoring serum glucose levels within the patient;

wherein the measuring, releasing, inhaling and monitoring steps are continuously repeated in a manner so as to maintain a desired serum glucose level in the patient.

2. The method of claim 1, wherein information obtained from the monitoring is electronically processed by a microprocessor programmed to release insulin in a manner so as to maintain a desired serum glucose level in the patient.

3. The method of claim 1, further comprising:

repeating the measuring prior to each releasing, inhaling and monitoring step over a period of time so as to maintain a desired serum glucose level in the patient.

4. The method of claim 1, wherein the insulin is recombinantly produced human insulin.

5. The method of claim 1, wherein the insulin is extracted from an animal source selected from the group consisting of bovine and porcine.

6. A method of intrapulmonary administration of insulin, comprising:

measuring the inspiratory flow of a patient during an inhalation cycle prior to administering insulin and calculating a threshold level of airflow prior to administering insulin, wherein the threshold level of inspiratory flow is determined in a manner so as to maximize repeatability of the amount of insulin delivered to the patient on releasing insulin;

administering insulin to the patient by the intrapulmonary route, the insulin being administered from a hand-held, self-contained device which releases insulin on detecting the threshold level of inspiratory flow created by patient inhalation;

monitoring serum glucose levels in the patient; and

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

7. The method as claimed in claim 6, wherein the amount of insulin administered and the glucose level monitored are continually recorded electronically by the self-contained device and adjustments are made in the amount of insulin administered based on the effect of insulin administration on the glucose levels of the patient.

8. The method as claimed in claim 6, wherein the amount of insulin administered is in the range of 1 unit per day to 50 units per day.

9. The method as claimed in claim 6, wherein the desired serum glucose level in the patient is within the range of 50 mg/dl to 300 mg/dl.

10. The method as claimed in claim 6, wherein the insulin is recombinantly produced human insulin.

11. The method as claimed in claim 6, wherein the insulin is insulin extracted from an animal source group consisting of a bovine source and a porcine source.

12. The method of claim 6, further comprising:

orally administering a sulfonylurea drug to the patient.

13. The method of claim 12, wherein the sulfonylurea drug is selected from the group consisting of acetohexamide, chlorpropamide, tolazamide, tolubutamide, glipzide and glyburide.

14. The method of claim 6, wherein the monitoring is carried out prior to each dosing event, wherein insulin is administered to the patient.

15. A method of intrapulmonary administration of insulin, comprising:

placing a mouthpiece of a hand-held, metered dose inhaler device in the mount of a patient, wherein the device is comprised of a container having therein insulin and a low boiling point propellant, a valve for releasing insulin and propellant from the container to the mouthpiece, a means for measuring airflow created by drawing air from the mouthpiece and a means for opening the valve in response to a measured threshold of airflow;

drawing air from the mouthpiece until a threshold is reached so as to cause the valve to open and release a controlled amount of insulin and propellant which is drawn into the lungs of the patient, wherein the device includes a microprocessor connected to the means for measuring airflow and means for opening the valve, the microprocessor being programmed to control the amount of insulin released, based on the needs of the patient, wherein the threshold level is a level calculated to obtain maximum reproducibility in the amount of insulin delivered to the patient with each release of insulin.