WO1997027745B1

WO1997027745B1 - Method of diagnosis and treatment and related compositions and apparatus

Info

Publication number: WO1997027745B1
Application number: PCT/US1997/001576
Authority: WO
Filing date: 1997-01-29
Publication date: 1997-10-30
Anticipated expiration: 1998-07-31

Abstract

A method for treatment of a disease comprising vasospasm or other symptom alleviable by smooth muscle relaxation and a vasodilator delivery system. The figure is a TCD of MCA post nitroglycerine spray obtained during continuous monitoring.

Claims

23AMENDED CLAIMS[received by the International Bureau on 22 August 1997 (22.08.97); original claims 1-20 replaced by new claims 1-10 (3 pages)]

1. A method for the treatment of chronic noncardiac diseases comprising vasospasm or other symptom alleviatable by smooth muscle relaxation, comprising in combination: a) measuring blood flow in at least one area; b) administering a first dosage of a vasodilator; c) remeasuring blood flow, and; d) administering a further dosage of a vasodilator, said further dosage being adjusted in response to the remeasured blood flow; e) continuing said treatment over a period of days while titrating said dosage according to still further measurements of blood flow to maintain optimal blood flow velocity.

2. A method according to Claim 1 wherein the measuring comprises a technique selected from the group consisting of Transcranial Doppler (TCD), quantitative electroencephalogram and determining relative vessel diameter.

3. A method according to Claim 1 wherein the blood flow is measured as Mean Fluid Velocity (MFV) in at least one intracranial vessel and wherein the MFV rises above about 0.4 meters/minute during vasospasms.

4. A method according to Claim 1 wherein the vasodilator is selected from the group consisting of nitroglycerin in pill, patch, ointment, cream, inhaler, spray and other forms, nitroglycerin equivalents and substitutes, such as p.o. clonidine, Dynacirc (isradipine), hydrazine, nifedipine, and medicines from the empirical group of medications which have the common characteristic of causing smooth muscle relaxation and which systemically reduce pulmonary capillary wedge pressure, and combinations of the foregoing.

5. A method according to Claim 1 wherein the disease is selected from the group consisting of whiplash, closed head injury with vasospasm, attention deficit disorder with vasospasm, migraine with inter-octal evidence of vasospasm, syncope or blackout spells of unknown aetiology with evidence of vasospasm, seizure with evidence of vasospasm, and dementia with evidence of vasospasm, concussion and post-concussion syndrome with evidence of vasospasm, migraine, sympathetic vasospasm associated with breast implants, and cerebral vasospasm. fibromyalgia, gastric disorders and other systemic disorders, psychosis, other psychiatric disease, attention deficit disorder dyslexia, memory disturbances, depression, psychosis, reflex sympathetic dystrophy, mood disorders and sensory motor disorders; transient ischemic attack (TIA), pseudoseizure, hemibalism, and stroke; tremor, Parkinson's disease, torticollis, electrical shock trauma, attention deficit disorder, concussion and post concussion syndrome, comprising vasospasm as a component..

6. A method of treatment of intracranial vasospasms comprising intermittent application of a vasodilator and reducing dosage as the vasospasms reduce in frequency and/or severity.

7. A method of Claim 1 wherein the treatment is applied to a patient who presents with transient or continuous TCD Mean Flow Velocities (MFV) of greater than 0.3 meters per second and wherein the treatment is continued for from about 5 to 250 weeks.

8.A vasodilator delivery system specially adapted to deliver about 5 to 25% of conventional dosage of vasodilators and marked with the appropriate DRG and/or ICD 9th. codes and/or instructions for titrating or tapering their use, to facilitate their proper application for treatment of diseases involving vasospasms.

9. A delivery system according to Claim 8 adapted for delivery of about 0.02 to 20 milligrams per day (Nitroglycerin equivalent) of a vasodilator selected from the group comprising Nitroglycerin in pill, patch, ointment, cream, inhaler, spray and other forms, Nitroglycerin equivalents and substitutes, comprising p.o. clonidine, Dynacirc (isradipine), hydrazine, nifedipine, and/or other medicines selected from the empirical group of medications which have the common characteristic of causing smooth 25 muscle relaxation and/or which systemically reduce pulmonary capillary wedge pressure, and combinations of the foregoing.

10. A method for diagnosing and treating a chronic noncardiac disease caused at least partially by insufficient cerebral perfusion, comprising in combination: testing for presence of a continued diastolic flow beyond end diastolic velocity as an indication of vasospasm, administering a vasospasm-reducing dosage of a medicine selected from the empirical group of medications which have the common characteristic of causing smooth muscle relaxation and/or which reduce pulmonary capillary wedge pressure, repeating said testing over time and titrating said dosage to minimize occurrence and severity of said vasospasms.

26 STATEMENT UNDER ARTICLE 19

The Amendments insert —chronic noncardiac diseases— into Claims 1 and 10 merely to add more focus on the diseases for which the invention has been found to be unexpectedly valuable. Use of vasodilators for treatment of cardiac diseases is well known, e.g. as shown by several of the Documents. The techniques of the invention are applicable to chronic, rather than acute, diseases as shown by the Examples and by Appendix A.

The Amendments also reduce the number of Claims to 10 for purposes of avoiding extra fees.