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|Title:||Pulmonary delivery of active fragments of parathyroid hormone|
|Abstract:||Systemic delivery of parathyroid hormone to a mammalian host is accomplished by inhalation through the mouth of a dispersion of an N-terminal fragment of PTH. It has been found that such respiratory delivery of the PTH fragment provides a pulsatile concentration profile of the PTH in the host's serum. PTH fragment compositions include dry powder formulations having the PTH present in a dry bulking powder, liquid solutions or suspensions suitable for nebulization, and aerosol propellants suitable for use in a metered dose inhaler.|
|Inventor(s):||Patton; John S. (San Carlos, CA)|
|Assignee:||Inhale Therapeutic Systems (Palo Alto, CA)|
|Filing Date:||Apr 25, 1994|
|Claims:||1. A method for pulsatile systemic delivery of an N-terminal peptide fragment of parathyroid hormone (PTH) to a mammalian subject, wherein said peptide fragment consists of the first 34 amino acids of SEQ ID NO. 1, and wherein said method comprises inhalation of a dispersion of said peptide fragment through the mouth of said subject resulting in administration of the peptide fragment to the alveolar region of the lungs and a subsequent rapid rise followed by a rapid fall in the serum concentration of said peptide fragment. |
2. A method as in claim 1, wherein the total dosage of the PTH fragment is in the range from 100 .mu.g to 2,000 .mu.g per day, resulting in systemic availability in the range from 50 .mu.g to 500 .mu.g per day.
3. A method as in claim 1, wherein the PTH fragment dispersion comprises a dry powder including a bulking agent.
4. A method as in claim 1, wherein the PTH fragment dispersion comprises a nebulized liquid solution or suspension of the PTH fragment.
5. A method as in claim 1, wherein the PTH fragment dispersion comprises a dry powder and an aerosol propellant.
6. A method for pulsatile systemic delivery of an active fragment of parathyroid hormone (PTH) to a patient, said method comprising:
(a) dispersing a preselected amount of the PTH fragment consisting of amino acids 1-34 of SEQ ID No: 1 in a volume of gas to produce an aerosolized bolus;
(b) inhaling of the aerosolized bolus by the patient through the mouth and into the alveolar region of the lungs; and
repeating steps (a) and (b) a sufficient number of times until a desired total dosage of PTH fragment is delivered.
7. A method as in claim 6, wherein the aerosolized bolus contains from about 50 .mu.g to 500 .mu.g of the PTH fragment and the total dosage is from about 100 .mu.g to 2,000 .mu.g per day, resulting in systemic availability in serum in the range from 50 .mu.g to 500 .mu.g per day.
8. A method as in claim 6, wherein the aerosolized bolus has a volume in the range from 10 ml to 750 ml.
9. A method as in claim 6, wherein the PTH fragment is dispersed in an aerosol of particles in the size range from 0.5 .mu.m to 5 .mu.m.
10. A method as in claim 6, wherein the PTH fragment comprises a dry powder present in a bulking agent, and dispersing comprises introducing the dry powder into a high velocity gas stream.
11. A method as in claim 6, wherein the PTH fragment comprises a liquid solution or suspension, and dispersing comprises nebulization of the liquid.
12. A method as in claim 6, wherein the PTH fragment comprises a liquid or powder present in a propellant, and dispersing comprises releasing the propellant through a nozzle to produce the dispersion.