Treatment of conditions through pharmacological modulation of the autonomic nervous system

• US 9,585,851 B2
• Filed: 04/24/2012
• Issued: 03/07/2017
• Est. Priority Date: 10/08/2003
• Status: Active Grant

• Current Assignee: Palo Alto Investors
• Original Assignee: Palo Alto Investors
• Inventors: Yun, Anthony Joonkyoo, Lee, Patrick Yuarn-Bor
• Primary Examiner(s): Ramachandran, Uma
• Application Number:
  US13/454,902
• Publication Number:
  US 20120270876A1
• Time in Patent Office: 1,778 Days
• Field of Search: 514/236.2, 514/411, 514/415, 514/538, 514/605, 514/620, 514/652, 607/3
• US Class Current: 1/1
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/166 having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/255 of sulfoxy acids or sulfur analogues thereof
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61N 1/36007 of urogenital or gastrointestinal organs, e.g. for incontinence control
• CPC Class Codes: A61N 1/3606 adapted for a particular treatment
• CPC Class Codes: A61N 1/36062 Spinal stimulation
• CPC Class Codes: A61N 1/36071 Pain
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: G16H 20/10 : relating to drugs or medications, e.g. for ensuring correct administration to patients

Abstract

Methods are provided for treating a subject for a condition caused by an abnormality in the subject'"'"'s autonomic nervous system. In accordance with the subject methods, at least a portion of a subject'"'"'s autonomic nervous system is pharmacologically modulated with at least one beta-blocker in a manner that is effective to treat the subject for the condition. The subject methods find use in the treatment of a variety of different conditions, where such conditions include various disease conditions. Also provided are systems and kits for use in practicing the subject methods.

Claims

1. A method of modulating the autonomic nervous system of a subject having an orthopedic inflammatory condition caused by an abnormal balance of the sympathetic and parasympathetic functions of the autonomic nervous system comprising:

determining the state of the subject'"'"'s autonomic nervous system by measuring a parasympathetic activity/sympathetic activity ratio in at least a portion of the subject'"'"'s autonomic nervous system; and

administering to the subject an effective amount of at least one beta-blocker chosen from atenolol, betaxolol, bisoprolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, pindolol, propranolol, sotalol, timolol, acebutalol, oxprenolol, carvedilol, and penbutolol, based on the determined state of the subject'"'"'s autonomic nervous system to inhibit activity in at least a portion of the subject'"'"'s sympathetic nervous system to produce a parasympathetic activity/sympathetic activity ratio in at least a portion of the subject'"'"'s autonomic nervous system that is analogous to the parasympathetic activity/sympathetic activity ratio observed in a healthy 25 year old human subject and reduce at least one symptom associated with the orthopedic inflammatory condition caused by the abnormal balance of the sympathetic and parasympathetic functions of the autonomic nervous system, wherein the orthopedic inflammatory condition is osteoarthritis.

2. The method according to claim 1, wherein the orthopedic inflammatory condition is characterized by a sympathetic bias.

3. The method according to claim 2, wherein the condition is characterized by normal sympathetic activity.

4. The method according to claim 2, wherein the orthopedic inflammatory condition is characterized by abnormally high sympathetic activity.

5. The method according to claim 1, further comprising increasing the parasympathetic activity/sympathetic activity ratio in the portion of the subject'"'"'s autonomic nervous system.

6. The method according to claim 5, further comprising increasing the parasympathetic activity.

7. The method according to claim 5, further comprising decreasing the sympathetic activity.

8. The method according to claim 1, wherein the at least one beta-blocker is administered orally at least once a day to the subject.

9. The method according to claim 1, wherein the administering is for a period of at least 24 hours.

10. The method according to claim 1, wherein the method further comprises employing a control feedback loop.

11. The method according to claim 10, wherein the control feedback loop maintains the parasympathetic activity/sympathetic activity ratio that is analogous to the parasympathetic activity/sympathetic activity ratio observed in a healthy 25 year old human subject in at least a portion of the autonomic nervous system, such that the modulating is repeated one or more times.

12. The method according to claim 10, wherein the modulating comprises administering at least two different beta-blocker protocols.

13. The method according to claim 1, further comprising stimulating at least a portion of the subject'"'"'s autonomic nervous system.

14. The method according to claim 13, wherein the stimulating comprises contacting at least a portion of the subject'"'"'s autonomic nervous system with at least one electrode and applying electrical energy to at least a portion of the subject'"'"'s autonomic nervous system.

15. The method according to claim 1, wherein the at least one beta-blocker is administered in an amount ranging from about 0.5 milligrams to about 1200 milligrams a day.

16. The method according to claim 1, wherein the at least one beta-blocker is betaxolol.