Treatment of conditions through modulation of the autonomic nervous system during at least one predetermined menstrual cycle phase

• US 20050256028A1
• Filed: 05/13/2004
• Published: 11/17/2005
• Est. Priority Date: 05/13/2004
• Status: Active Grant

• Current Assignee: Palo Alto Investors
• Original Assignee: Palo Alto Investors
• Inventors: Lee, Patrick Yuarn-Bor, Yun, Anthony Joonkyoo
• Granted Patent: US 7,899,527 B2
• Time in Patent Office: Days
• US Class Current: 332/128
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 38/085 Angiotensins
• CPC Class Codes: A61K 38/095 Oxytocins; Vasopressins; Related peptides
• CPC Class Codes: A61K 38/2221 Relaxins
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/4813 Exopeptidases (3.4.11. to 3.4.19)
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

Methods are provided for treating a subject for a condition. In accordance with the subject methods, at least a portion of a subject'"'"'s autonomic nervous system is modulated during at least one predetermined phase of the subject'"'"'s menstrual cycle to alter the parasympathetic activity/sympathetic activity ratio 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, including various disease conditions, that increase in severity and/or occurrence during one or more phases of the menstrual cycle. Also provided are systems and kits for use in practicing the subject methods.

Claims

1. A method of treating a subject for a condition comprising modulating at least a portion of the autonomic nervous system of said subject during at least one predetermined menstrual cycle phase of said subject to increase or decrease the parasympathetic activity/sympathetic activity ratio in a manner effective to treat said subject for said condition.

2. The method according to claim 1, wherein said condition is a disease condition.

3. The method according to claim 1, wherein said condition is characterized by an abnormal decrease in said parasympathetic activity/sympathetic activity ratio during said at least one phase.

4. The method according to claim 1, wherein said condition is characterized by an abnormal increase in said parasympathetic activity/sympathetic activity ratio during said at least one phase.

5. The method of claim 1, wherein said method comprises increasing said parasympathetic activity/sympathetic activity ratio.

6. The method of claim 5, wherein said method comprises increasing parasympathetic activity.

7. The method of claim 5, wherein said method comprises decreasing sympathetic activity.

8. The method of claim 5, wherein said method comprises increasing parasympathetic activity and decreasing sympathetic activity.

9. The method of claim 1, wherein said method comprises decreasing said parasympathetic activity/sympathetic activity ratio.

10. The method of claim 9, wherein said method comprises decreasing parasympathetic activity.

11. The method of claim 9, wherein said method comprises increasing sympathetic activity.

12. The method of claim 9, wherein method comprises decreasing parasympathetic activity and increasing sympathetic activity.

13. The method of claim 1, wherein said modulation is accomplished by at least applying electrical energy to said at least one portion of said autonomic nervous system.

14. The method of claim 13, wherein said application of electrical energy comprises electrically increasing activity in at least one portion of said autonomic nervous system.

15. The method of claim 13, wherein said application of electrical energy comprises electrically inhibiting activity in at least one portion of said autonomic nervous system.

16. The method of claim 1, wherein said modulation is accomplished by at least administering an effective amount of at least one pharmacological agent to said subject.

17. The method of claim 16, wherein said at least one pharmacological agent is chosen from:

beta-blockers;

aldosterone antagonists;

angiotensin II receptor blockades;

angiotensin converting enzyme inhibitors;

statins;

triglycerides lowering agents;

niacin;

diabetes agents;

immunomodulators;

nicotine;

sympathomimetics;

antihistamines;

cholinergics;

acetylcholinesterase inhibitors;

magnesium and magnesium sulfates;

calcium channel blockers;

muscarinics;

sodium channel blockers;

glucocorticoid receptor blockers;

blood vessel dilators;

central agonists;

combined alpha and beta-blockers;

alpha blockers;

combination diuretics;

potassium sparing diuretics;

cyclic nucleotide monophosphodiesterase inhibitors;

alcohols;

vasopressin inhibitors;

oxytocin inhibitors;

glucagons like peptide 1;

relaxin hormone;

renin inhibitors;

estrogen and estrogen analogues and metabolites;

progesterone inhibitors;

testosterone inhibitors;

gonadotropin-releasing hormone analogues;

gonadotropin-releasing hormone inhibitors;

type 4 phosphodiesterase inhibitors;

vesicular monoamine transport inhibitors;

melatonin;

anticoagulants;

beta agonists;

alpha agonists;

indirect agents that include norepinephrine;

epinephrine;

norepinephrine;

acetylcholine;

sodium;

calcium;

angiotensin I;

angiotensin II;

angiotensin converting enzyme I;

angiotensin converting enzyme II;

aldosterone;

potassium channel blockers and magnesium channel blockers;

cocaine;

amphetamines;

ephedrine;

terbutaline;

dopamine;

doputamine;

antidiuretic hormone;

oxytocin; and

THC cannabinoids.

18. The method of claim 17, wherein said method comprises increasing said parasympathetic activity/sympathetic activity ratio and said at least one pharmacological agent is chosen from the group of:

beta-blockers;

aldosterone antagonists;

angiotensin II receptor blockades;

angiotensin converting enzyme inhibitors;

statins;

triglycerides lowering agents;

niacin;

diabetes agents;

immunomodulators;

nicotine;

sympathomimetics;

antihistamines;

cholinergics;

acetylcholinesterase inhibitors;

magnesium and magnesium sulfates;

calcium channel blockers;

muscarinics;

sodium channel blockers;

glucocorticoid receptor blockers;

blood vessel dilators;

central agonists;

combined alpha and beta-blockers;

alpha blockers;

combination diuretics;

potassium sparing diuretics;

cyclic nucleotide monophosphodiesterase inhibitors;

alcohols;

vasopressin inhibitors;

oxytocin inhibitors;

glucagons like peptide 1;

relaxin hormone;

renin inhibitors;

estrogen and estrogen analogues and metabolites;

progesterone inhibitors;

testosterone inhibitors;

gonadotropin-releasing hormone analogues;

gonadotropin-releasing hormone inhibitors;

type 4 phosphodiesterase inhibitors;

vesicular monoamine transport inhibitors;

melatonin; and

anti-coagulants.

19. The method of claim 17, wherein said method comprises decreasing said parasympathetic activity/sympathetic activity ratio and said at least one pharmacological agent is chosen from the group of:

beta agonists;

alpha agonists;

indirect agents that include norepinephrine;

epinephrine;

norepinephrine;

acetylcholine;

sodium;

calcium;

angiotensin I;

angiotensin II;

angiotensin converting enzyme I;

angiotensin converting enzyme II;

aldosterone;

potassium channel blockers and magnesium channel blockers;

cocaine;

amphetamines;

ephedrine;

terbutaline;

dopamine;

doputamine;

antidiuretic hormone;

oxytocin; and

THC cannabinoids.

20. The method of claim 16, wherein said menstrual cycle is an about 28 day menstrual cycle and said method comprises administering an effective amount of said at least one pharmacological agent to said subject substantially throughout said about 28 days, wherein said dosage is increased or decreased during said at least one predetermined phase of said menstrual cycle.

21. The method of claim 1, wherein said method further comprises determining said parasympathetic activity/sympathetic activity ratio at least one time during said menstrual cycle.

22. The method of claim 21, wherein said parasympathetic activity/sympathetic activity ratio is determined at least one time during said at least one predetermined phase of said menstrual cycle

23. The method of claim 21, further comprising performing said modulation of said at least one portion of the autonomic nervous system based on said determined parasympathetic activity/sympathetic activity ratio.

24. The method of claim 1, wherein said at least one predetermined menstrual cycle phase is the menses phase.

25. The method of claim 1, wherein said at least one predetermined menstrual cycle phase is the follicular phase.

26. The method of claim 1, wherein said at least one predetermined menstrual cycle phase is the ovulation phase.

27. The method of claim 1, wherein said at least one predetermined menstrual cycle phase is the luteal phase.

28. The method of claim 27, wherein said luteal phase is the late luteal phase.

29. The method according to claim 1, wherein said condition is chosen from cardiovascular conditions;

neurodegenerative conditions;

neuroinflammatory conditions;

orthopedic inflammatory conditions;

lymphoproliferative conditions;

autoimmune;

inflammatory conditions;

infectious diseases;

pulmonary conditions;

transplant-related conditions;

gastrointestinal conditions;

endocrine conditions;

genitourinary conditions;

skin conditions;

aging conditions;

neurologic conditions;

Th-2 dominant conditions;

conditions that cause hypoxia;

conditions that cause hypercarbia;

conditions that cause hypercapnia;

conditions that cause acidosis;

conditions that cause acidemia;

OB-GYN conditions;

sudden death syndromes;

menstrual related disorders;

peripartum and pregnancy related disorders;

fibrosis;

post-operative recovery conditions;

post-procedural recovery conditions;

chronic pain;

trauma;

bacterial infections; and

fibromyalgia.

66. A kit comprising:

(a) at least one of;

an electrical energy applying device and at least one pharmacological agent, and

(b) instructions of using said at least one of an electrical energy applying device and at least one pharmacological agent in a method according to claim 1.

67. The kit of claim 66, wherein said kit comprises a plurality of daily unit doses of a pharmacological agent and said daily unit dosage of at least two of said plurality are different.

68. The kit of claim 66, wherein said kit comprises a plurality of daily unit doses of said pharmacological agent substantially corresponding to each day of said menstrual cycle, wherein the daily unit doses of said pharmacological agent to be administered to said subject during a predetermined menstrual cycle phase differs from the daily unit dosages of said pharmacological agent to be administered throughout at least one other menstrual cycle phases.

30. The method of claim 30, wherein said condition is a neurodegenerative condition chosen from the group of:

Alzheimer'"'"'s Disease, Pick'"'"'s Disease, Parkinson'"'"'s Disease, dementia, delirium, and amyotrophic lateral sclerosis.

31. The method of claim 30, wherein said condition is a neuroinflammatory condition chosen from the group of:

viral meningitis, viral encephalitis, fungal meningitis, fungal encephalitis, multiple sclerosis, charcot joint, schizophrenia, and myasthenia gravis.

32. The method of claim 30, wherein said condition is an orthopedic inflammatory condition chosen from the group of:

osteoarthritis, inflammatory arthritis, regional idiopathic osteoporosis, reflex sympathetic dystrophy, Paget'"'"'s disease, osteoporosis, antigen-induced arthritis, and juvenile chronic arthritis.

33. The method of claim 30, wherein said condition is a lymphoproliferative condition chosen from the group of:

lymphoma, lymphoproliferative disease, Hodgkin'"'"'s disease, and inflammatory pseudomotor of the liver.

34. The method of claim 30, wherein said condition is an autoimmune condition chosen from the group of:

Graves-disease, raynaud'"'"'s, hashimoto'"'"'s, takayasu'"'"'s disease, kawasaki'"'"'s diseases, arteritis, scleroderma, CREST syndrome, allergies, dermatitis, Henoch-schlonlein purpura, goodpasture syndrome, autoimmune thyroiditis, myasthenia gravis, Reiter'"'"'s disease, and lupus.

35. The method of claim 30, wherein said condition is an inflammatory condition chosen from the group of:

ARDS, multiple sclerosis, rheumatoid arthritis, juvenile rheumatoid arthritis, juvenile chronic arthritis, migraines, and chronic headaches.

36. The method of claim 30, wherein said condition is an infectious disease chosen from the group of:

sepsis, viral and fungal infections, diseases of wound healing, wound healing, tuberculosis, infection, AIDS, and human immunodeficiency virus.

37. The method of claim 30, wherein said condition is a pulmonary condition chosen from the group of:

tachypnea, fibrotic lung diseases, interstitial lung disease, desquamative interstitial pneumonitis, non-specific interstitial pneumonitis, lymphocytic interstitial pneumonitis, usual interstitial pneumonitis, idiopathic pulmonary fibrosis, pulmonary edema, aspiration, asphyxiation, pneumothorax, right-to-left shunts, left-to-right shunts, and respiratory failure.

38. The method of claim 30, wherein said condition is a transplant-related condition chosen from the group of:

transplant related side effects, transplant rejection, transplant-related tachycardia, transplant related renal failure, transplant related bowel dysmotility, and transplant-related hyperreninemia.

39. The method of claim 30, wherein said condition is a gastrointestinal condition chosen from the group of:

hepatitis, xerostomia, bowel mobility, peptic ulcer disease, constipation, ileus, irritable bowel syndrome, post-operative bowel dysmotility, inflammatory bowel disease, typhilitis, cholelethiasis, cholestasis, fecal incontinence, and cyclic vomiting syndrome.

40. The method of claim 30, wherein said condition is an endocrine condition chosen from the group of:

hypothyroidism, hyperglycemia, diabetes, obesity, syndrome X, insulin resistance, and polycycstic ovarian syndrome.

41. The method of claim 30, wherein said condition is a genitourinary condition chosen from the group of:

bladder dysfunction, renal failure, hyperreninemia, hepatorenal syndrome, pulmonary renal syndrome, incontinence, arousal disorder, menopausal mood disorder, premenstrual mood disorder, renal tubular acidosis, and pulmonary renal syndrome.

42. The method of claim 30, wherein said condition is a skin condition chosen from the group of:

wrinkles, cutaneous vasculitis, and psoriasis.

43. The method of claim 30, wherein said condition is an aging associated condition chosen from the group of:

shy dragers, multi-system atrophy, age related inflammation conditions, cancer, and aging.

44. The method of claim 30, wherein said condition is a neurologic condition chosen from the group of:

epilepsy, depression, schizophrenia, seizures, stroke, insomnia, cerebral vascular accident, transient ischemic attacks, stress, bipolar disorder, concussions, post-concussive syndrome, cerebral vascular vasospasm, central sleep apnea, obstructive sleep apnea, sleep disorders, headaches incuding chronic headaches, migraines, and acute disseminated encephalomyelitis.

45. The method of claim 30, wherein said condition is aTh-2 dominant condition chosen from the group of:

typhilitis, osteoporosis, lymphoma, myasthenia gravis, and lupus.

46. The method of claim 30, wherein said condition is a condition that causes at least one of:

hypoxia, hypercarbia, hypercapnia, acidosis and acidemia.

47. The method of claim 46, wherein said conditions is chosen from the group of:

Chronic Obstructive Pulmonary Disease, V/Q mismatch, emphysema, a chronic lung disease that causes acidosis, acute pulmonary embolism, sudden adult death syndrome, chronic pulmonary embolism, pleural effusion, cardiogenic pulmonary edema, non-cardiogenic pulmonary edema, acute respiratory distress syndrome, neurogenic edema, hypercapnia, acidemia, asthma, renal tubular, asthma, acidosis, a chronic lung diseases that causes hypoxia, a chronic lung diseases that causes hypercarbia, and a chronic lung diseases that causes hypercapnia.

48. The method of claim 30, wherein said condition is an OB-GYN chosen from the group of:

amniotic fluid embolism, menopausal mood disorders, premenstrual mood disorders, pregnancy-related arrhythmias, fetal stress syndrome, fetal hypoxia, amniotic fluid embolism, gestational diabetes, pre-term labor, cervical incompetence, fetal distress, peri-partum maternal mortality, peripartum cardiomyopathy, labor complications, premenstrual syndrome, dysmenorrheal, infertility, early pregnancy loss, spontaneous abortion, subfertility, failure of implantation, amenorrhea, luteal insufficiency, and endometriosis.

49. The method of claim 30, wherein said condition is sudden adult death syndrome.

50. The method of claim 30, wherein said condition is a menstrual related disorders chosen from the group of:

pelvic pain, dysmenorrheal, gastrointestinal disease, and nausea.

51. The method of claim 30, wherein said condition is a peripartum condition.

52. The method of claim 30, wherein said condition is a pregnancy related condition.

53. The method of claim 52, wherein said pregnancy related condition is peripartum cardiomyopathy.

54. The method of claim 30, wherein said condition is fibrosis.

55. The method of claim 30, wherein said condition is a post-operative recovery condition chosen from the group of:

post-operative pain, post operative ileus, post-operative fever, and post-operative nausea.

56. The method of claim 30, wherein said condition is a post-procedural recovery condition chosen from the group of:

post-procedural pain, post procedural ileus, post-procedural fever, and post-procedural nausea.

57. The method of claim 30, wherein said condition is a chronic pain.

58. The method of claim 30, wherein said condition is a trauma.

59. The method of claim 30, wherein said condition is hospitalization.

60. The method of claim 30, wherein said condition is glaucoma.

61. The method of claim 30, wherein said condition is a disorder of thermoregulation.

62. The method of claim 30, wherein said condition is fibromyalgia.

63. The method of claim 30, wherein said condition is a cardiovascular conditions chosen from the group of:

atherosclerosis, coronary artery disease, hypertension, hyperlipidemia, eclampsia, pre-eclampsia, cardiomyopathy, volume retention, congestive heart failure, QT interval prolongation, aortic dissection, aortic aneurysm, arterial aneurysm, arterial vasospasm, myocardial infarction, reperfusion syndrome, ischemia, sudden adult death syndrome, arrhythmia, fatal arrythmias, coronary syndromes, coronary vasospasm, sick sinus syndrome, bradycardia, tachycardia, thromboembolic disease, deep vein thrombosis, coagulopathy, disseminated intravascular coagulation, mesenteric ischemia, syncope, venous thrombosis, arterial thrombosis, malignant hypertension, secondary hypertension, primary pulmonary hypertension, secondary pulmonary hypertension, raynaud'"'"'s, paroxysmal supraventricular, and tachycardia.

64. The method of claim 30, wherein said condition is a bacterial infection.

65. The method of claim 65, wherein said bacterial infection is bacterial vaginosis.