Combination of a .beta.-receptor blocker and a local anaesthetic

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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Details

514626, 514652, 514817, 514818, A61K 31445

Patent

active

058563423

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/SE95/00314, filed Mar. 24, 1995.


FIELD OF THE INVENTION

The present invention is related to improvements in pain relief. More particularly it relates to the use of .beta.-receptor blockers, especially alprenolol and metoprolol, or a pharmaceutically acceptable salt thereof, alone or in combination with a local anaesthetic or a pharmaceutically acceptable salt thereof, for the treatment of pain, and to pharmaceutical compositions containing the two active ingredients.


BACKGROUND OF THE INVENTION

Pain is maybe the most feared and disabling consequence of illness and trauma. It is also the most frequent reason why patients seek medical consultation. It has been estimated that pain costs the US economy at least 600 BSEK (billion Swedish crowns). Only recently this enormous and costly human suffering has obtained significant attention among the medical community and researches. The attention will continue to grow as the great therapeutic need is obvious, pain increases as population ages. Pain research has recently made major progress.
Some examples of pain indications are postoperative pain, diabetic neurophathia and cancer pain.
Postoperative pain is one of the most frequent types of acute pain and generally undertreated. Thus, 80.000 surgical procedures per million inhabitants take place per year and 75% suffer from postoperative pain.
Postoperative pain may be regarded as a specific variant of acute nociceptive pain. It is markedly different from cancer pain, chronic pain and neurogenic pain in pathophysiology, psychological correlation and therapeutic approaches.


______________________________________ Severe Moderate Mild Operative site pain pain pain ______________________________________ Thoracic 50 40 10 Upper/lower abd 35 45 20 Joints/orthopedic 60 30 10 Spine 25 50 25 Superficial head, neck, 20 35 45 chest TOTAL (%) 40 30 30 ______________________________________
Apart from the humanitarian aspects of relieving pain after surgery, there are physiological benefits to the patients.
Adverse effects of poorly controlled pain include: after operation. formation, slow intestinal motility and muscular wasting. myocardial ischemia.
A causal and effective therapy of diabetic neuropathy does not yet exist and currently available therapy offers limited success and unacceptable side effects. Neuropathy develops in more than two thirds of the diabetic patients in the course of the disease. The prevalence usually vary between 12% and 50% and the incidence and severity vary with age, duration of diabetes and possibly the quality of glycaemic control. The number of patients suffering from painful diabetic neuropathy in North America is estimated to be 2 millions. One of many problems caused by diabetes is nerve damage. This may result in pain that is insidious, sudden and acute, or a mixture of these traits.
The incidence of cancer has increased steadily for 20 years. In Sweden and in the US it is now 0.45% or 4500/million inhabitants and year who are taken ill in cancer. In the age group 60 years old it is 1% and then increases to 3% for 80 years old men. The incidence of cancer that causes severe pain is 0.16% or 1600 cases/million inhabitants per year, and 1.3 million worldwide.
Most cancer patients live for several years with their disease. Pain accompanies the disease most of the time and is frequently the original cause for consulting a medical doctor. The life expectancy of patients with advanced or terminal cancer varies from a few months to a few years. It has been found that the prevalence of pain in these patients varies between 55 and 90%, average 75%, depending mostly on the site of cancer.
The standard treatment for postoperative pain following major abdominal and orthopedic surgery consists normally of repeated injections of an opioid such as morphine given by ward nurses on request. This is generally recognized as an inferior technique since there is reluctance to administer the doses in the individual manner that both the pharmacokinetic and pha

REFERENCES:
patent: 5496811 (1996-03-01), Aviv et al.
Machtens et al., "Qualitative Probleme der Schmerzausschaltung durch kombinierte Gabe von beta-adrenolytischen Substanzen mit Lokalanasthetika," Dtsch. zahnarztl. Z. 28:1021-1025 (1973).
Capucci et al., "Tocainide and Metoprolol: An Efficacious Therapeuric Combination in the Treatment of Premature Ventricular Beats," Clin. Cardiol. 12:322-331 (1989).
Chemical Abstracts AN 1987:417566, Coram et al., Jan. 1987.

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