Methods for improving drug efficacy including a combination of drug administration and nerve modulation

• US 9,398,933 B2
• Filed: 12/27/2013
• Issued: 07/26/2016
• Est. Priority Date: 12/27/2012
• Status: Active Grant

• Current Assignee: Nuvaira, Inc.
• Original Assignee: Holaira, Inc. (Nuvaira, Inc.)
• Inventors: Mayse, Martin L.
• Primary Examiner(s): Weidner, Adam M
• Application Number:
  US14/142,350
• Publication Number:
  US 20140186341A1
• Time in Patent Office: 942 Days
• US Class Current: 1/1
• CPC Class Codes: A61B 17/32 Surgical cutting instruments A61B18/042 takes precedence; suture cutters A61B17/0467; instruments for ligaturing or cutting A61B17/128; instruments for rupturing the amniotic membrane A61B17/4208; specially adapted knives for eye surgery A61F9/0133
• CPC Class Codes: A61B 18/1492 having a flexible, catheter-like structure, e.g. for heart ablation A61B18/1477 takes precedence
• CPC Class Codes: A61B 18/18 by applying electromagnetic radiation, e.g. microwaves radiation therapy A61N5/00
• CPC Class Codes: A61B 2018/00023 closed, i.e. without wound contact by the fluid
• CPC Class Codes: A61B 2018/0022 Balloons
• CPC Class Codes: A61B 2018/00541 Lung or bronchi
• CPC Class Codes: A61B 2018/00577 Ablation
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61N 1/3611 Respiration control stimulating respiratory organs A61N1/3601

Abstract

The present disclosure provides methods for improving drug efficacy in a patient having an obstructed airway in a lung. Such methods modulate nerve activity in the autonomic nervous system of a patient to reduce obstruction of an airway in a lung of the patient prior to administering a drug to the patient. These methods are especially useful in improving efficacies of bronchodilators in treating obstructive lung diseases, such as chronic obstructive pulmonary disease.

Claims

1. A method for treating a patient having an obstructive lung disease, comprising:

(a) disrupting nerve activity in a parasympathetic nervous system of the patient to reduce obstruction in a distal airway in a lung of the patient; and

(b) while nerve activity is disrupted and the obstruction is reduced in the distal airway, administering a dose of an anticholinergic drug to the patient, the anticholinergic drug having a reference efficacy,

wherein a combination of steps (a) and (b) have a combined treatment efficacy greater than the reference efficacy of the anticholinergic drug.

2. The method of claim 1, wherein step (a) comprises stimulating a portion of the parasympathetic nervous system with electrical impulses to block nervous system signals from traveling past the portion of the parasympathetic nervous system.

3. The method of claim 1, wherein the anticholinergic drug is an inhaled drug.

4. The method of claim 1, wherein the anticholinergic drug is a non-inhaled drug.

5. The method of claim 1, wherein obstruction in the distal airway results from smooth muscle contraction, thickening of airway wall, mucous accumulation, or a combination thereof.

6. The method of claim 1, wherein the patient suffers from chronic obstructive pulmonary disease (COPD).

7. The method of claim 1, wherein the patient suffers from asthma.

8. The method of claim 1, wherein the patient suffers from cystic fibrosis.

9. The method of claim 1, wherein step (a) is performed without causing permanent damage to non-nerve tissue.

10. The method of claim 1, wherein step (a) comprises attenuating nerve activity in a portion of the parasympathetic nervous system of the patient.

11. The method of claim 1, wherein step (a) comprises stimulating nerve activity in a portion of the sympathetic nervous system of the patient.

12. The method of claim 1, wherein step (a) comprises disrupting activity in a nerve of a first airway of the patient which carries signals to or from the distal airway, wherein the distal airway is a higher generation airway of the first airway.

13. The method of claim 1, wherein step (a) comprises disrupting nerve activity of a pulmonary plexus.

14. The method of claim 1, wherein step (a) comprises disrupting nerve activity of a bronchial branch of the vagus nerve.

15. The method of claim 1, wherein step (a) comprises damaging a portion of the parasympathetic nervous system.

16. The method of claim 15, wherein damaging the portion of the parasympathetic nervous system comprises applying energy to the portion of the parasympathetic nervous system.

17. The method of claim 16, wherein applying energy to the portion of parasympathetic nervous system comprises applying thermal energy, microwave, electrical energy, cryogenic energy, acoustic energy, radio frequency energy, pulsed high voltage energy, mechanical energy, ionizing radiation, or optical energy to the portion of the parasympathetic nervous system.

18. The method of claim 16, wherein applying energy to the portion of parasympathetic nervous system does not cause permanent damage to any interior airway walls of the patient.

19. The method of claim 16, further comprising protecting an interior airway wall of the patient from permanent damage while applying the energy.

20. The method of claim 1, wherein step (a) comprises damaging a nerve trunk extending along a wall of an airway.

21. The method of claim 20, wherein step (a) comprises damaging a bronchial branch of the vagus nerve.

22. The method of claim 20, wherein the nerve trunk is damaged by delivering energy from an interventional device.

23. The method of claim 22, wherein the energy is delivered from within the airway.

24. The method of claim 22, wherein the energy is delivered from outside the airway.