Intrapulmonary delivery of hematopoietic drug

• US 6,012,450 A
• Filed: 07/01/1996
• Issued: 01/11/2000
• Est. Priority Date: 01/29/1993
• Status: Expired due to Fees

• Current Assignee: Aradigm Corporation
• Original Assignee: Aradigm Corporation
• Inventors: Rubsamen, Reid M.
• Primary Examiner(s): Lewis, Aaron J.
• Application Number:
  US08/673,963
• Time in Patent Office: 1,289 Days
• Field of Search: 128/200.14, 128/200.23, 128/204.23, 128/205.23, 128/203.12
• US Class Current: 128/200.14
• CPC Class Codes: A61J 7/0445 for preventing drug dispensing during a predetermined time period
• CPC Class Codes: A61M 15/001 using ultrasonic means
• CPC Class Codes: A61M 15/0045 using multiple prepacked dosages on a same carrier, e.g. blisters
• CPC Class Codes: A61M 15/0048 the dosages being arranged in a plane, e.g. on diskettes
• CPC Class Codes: A61M 15/0051 the dosages being arranged on a tape, e.g. strips
• 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 15/009 using medicine packages with incorporated spraying means, e.g. aerosol cans pocket atomiser of the injector type A61M11/08
• CPC Class Codes: A61M 16/108 before being humidified or mixed with a beneficial agent
• 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 2205/52 with memories providing a history of measured variating parameters of apparatus or patient
• CPC Class Codes: A61M 2205/8206 battery-operated

Abstract

A method of treating human patients is provided by the intrapulmonary delivery of a formulation containing a hematopoietic drug. The formulation is automatically released in an aerosolized form from a hand-held, self-contained, portable device comprised of a means for automatically releasing a measured amount of drug into the inspiratory flow path of a patient in response to information obtained from a means for measuring the inspiratory flow rate and determining the inspiratory volume of a patient. Reproducible dosing is obtained by providing for automatic release at the same inspiratory flow rate and inspiratory volume each time drug is released. The device includes a timer to enable a patient to take a drug at the same time each day. Further, overadministration of a hematopoietic drug formulation is avoided by providing a pre-programmed microprocessor designed to avoid overdosing.

Claims

1. A method of administering a therapeutically effective amount of a hematopoietic drug to a patient with a hand-held, self-contained, reusable device, the method comprising:

(a) determining the patient'"'"'s inspiratory flow profile based on real time values of both said patient'"'"'s inspiratory flow rate and inspiratory volume;

(b) determining a drug release point of said inspiratory flow profile, wherein at said drug release point said patient'"'"'s inspiratory flow rate is in a range of about 0.10 to about 2.0 liters/second and inspiratory volume is in a range of about 0.15 to about 0.8 liters;

(c) releasing an aerosolized dose of a hematopoietic drug containing 100 to 1,000,000 units of drug in a 0.01 to 1 ml of drug formulation within the determined ranges of inspiratory flow rate and inspiratory volume combinations, wherein the aerosolized dose comprises aerosolized particles having a diameter in the range of 1.0 to 12.0 microns and is released from a package comprising a porous membrane with pores having a diameter in the range of 0.5 to 6.0 microns;

(d) repeating steps (a), (b) and (c) in a manner such that the releasing repeatedly occurs within substantially the same ranges of inspiratory flow rate and inspiratory flow volume combinations;

(e) monitoring the amount of drug released and preventing overdosing by preventing further release of drug beyond a given amount within a given period of time; and

(f) providing a visual display to the patient of the amount of drug released.

2. The method of claim 1, wherein 20% or more of the released dose of aerosolized drug enters the circulatory system of the patient.

3. The method of claim 2, wherein 30% or more of the released dose of hematopoietic drug enters the circulatory system of the patient.

4. The method of claim 1, wherein the repeating of (d) is carried out until a therapeutically effective increase in the red blood cell level of the patient is obtained.

5. The method of claim 4, wherein the repeating of (d) is continuously carried out so as to obtain a red blood cell level in the range of about 3.9 to 6.0×

10^-6 erythrocytes per microliter of blood.

6. The method of claim 1, further comprising:

sending an audible signal to the patient at a predetermined time so as to prompt the patient to administer drug.

7. The method of claim 1, wherein the repeating of (c) is carried out over a period of time so as to maintain a desired drug to blood ratio in the patient.

8. The method of claim 1, wherein the hematopoietic drug is a non-naturally-occurring polypeptide having an amino acid sequence sufficiently duplicative of that of naturally-occurring stem cell factor to allow possession of a hematopoietic biological activity of naturally occurring stem cell factor.

9. The method of claim 1, wherein the hematopoietic drug is a combination of hIL-3 and hSCF.

10. The method of claim 1, wherein the hematopoietic drug is selected from the group consisting of CSF, EPO, G-CSF, CSF-1, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IGF-1, and LIF (leukemic Inhibitory Factor) and combinations thereof.

11. The method as claimed in claim 1, wherein the hematopoietic drug is isolated, purified, naturally-occurring human stem cell factor.

12. The method as claimed in claim 1, wherein the hematopoietic drug is a combination of hGM-CSF and hCSF.

13. The method as claimed in claim 1, wherein the amount of hematopoietic drug administered and time of administration is continually recorded and adjustments are made in the amount of drug administered based on the effect of drug administration on the red blood cell level of the patient.

14. The method as claimed in claim 1, wherein the hematopoietic drug is human recombinant EPO and is administered in an amount in the range of from about 50 to 100 U/kg of patient'"'"'s body weight.

15. The method as claimed in claim 1, wherein the aerosolized dose includes 25 μ

l to 100 μ

l of formulation which dose contains 25,000 to 100,000 units of drug and is administered three times each week.

16. The method of claim 13, further comprising:

retrieving the recorded information regarding the time and amount of hematopoietic drug administered; and

analyzing the retrieved information to determine desired dosing levels for further administration of hematopoietic drug to the patient.

17. A method of administering a therapeutically effective amount of a hematopoietic drug to a patient with a hand-held, self-contained, reusable device, the method comprising:

(a) determining the patient'"'"'s inspiratory flow profile;

(b) determining a drug release point of said inspiratory flow profile;

(c) releasing an aerosolized dose of a hematopoietic drug at said drug release point, wherein said aerosolized dose comprises aerosolized particles having a diameter in the range of 1.0 to 12.0 microns and is released from a disposable drug containing package comprising a porous membrane with pores having a diameter in the range of 0.5 to 6.0 microns; and

(d) repeating steps (a) thru (c) in a manner such that the releasing repeatedly occurs at substantially said drug release point.

18. The method according to claim 17, wherein the inspiratory flow rate of said patient at said drug release point is in a range of about 0.10 to about 2.0 liters/second and the inspiratory volume of said patient at said drug release point is in a range of about 0.15 to about 0.8 liters.