Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1994-05-18
1996-04-09
Chan, Christina Y.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
530322, A61K 3816, C07K 900
Patent
active
055062040
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the treatment and prophylaxis of sepsis, septic shock and other life-threatening inflammatory conditions.
The mortality of systemic bacterial infection (bacteraemia) is high, particularly for gram-negative infections, where mortality levels are still comparable to those of several decades ago. Hospital-acquired infections have a higher mortality than community-acquired infections; post-operative complications due to bacterial infections represent a real problem in many hospitals of the world. The mortality of gram-negative bacteraemia is frequently due to septic shock.
Septic shock (also known as toxic shock) is an acute life-threatening inflammatory condition characterised by hypotension and/or evidence of organ hypoperfusion. The hypotension results from reduced vascular resistance. Multiple organ failure and abnormalities of coagulation frequently develop.
Current management of septic shock includes intensive haemodynamic monitoring with aggressive fluid replacement if necessary to correct hypovolaemia, and the administration of inotropes to raise the blood pressure by increasing the cardiac output. Some of these drugs, particularly noradrenaline, also cause vasoconstriction, and so increase peripheral resistance. Additional supported measures are frequently required, including haemodialysis, mechanical ventilation and parenteral nutrition. The underlying infection is treated with anti-infective agents such as antibiotics or other antibacterials.
Other life-threatening inflammatory conditions include cachexia, which is a chronic condition which may arise from cancer or chronic infections, for example by viruses such as the HIV virus. Cachexia is characterised by abnormal lipid metabolism with hypertriglyceridaemia, abnormal protein and glucose metabolism and body wasting. It may also be implicated in systemic bacterial infections.
The invention also relates to other infections and inflammatory conditions such as pneumonia, surgical wound infection, suppuration of the small pelvis, peritonitis, peritoneal abscess, paracolostomic abscess, cholangitis, empyema of the gall bladder, phlegmon of front abdomen, phlegmon of the sigma and postinjective abscess, as well as to the related complications of endotoxaemia, glucose depression, hypotension, cardiac arrythmia and vasodilation.
There are today many impressive anti-infective agents available to the medical practitioner. Antibiotics form an important sub-group of antibacterials. Antibiotics are antibacterial agents derived from microorganisms; they include the penicillins, streptomycin, chloramphenicol and chlortetracycline. The discovery and isolation of the penicillin nucleus, 6-amino-penicillanic acid (6-APA) in 1958 provided the basis for the synthesis of a large number of new penicillins, many of which are still in use. Other antibacterials apart from antibiotics also form the basis of many treatment regimes: examples include the sulphonamides and trimethoprim, which are often co-administered.
Because of the continued increase and high incidence of life-threatening inflammatory conditions such as septic shock, it is apparent that the availability of a large number of chemotherapeutic agents including effective anti-bacterial drugs has not solved the problem of treating and preventing them. In fact, effective anti-bacterial chemotherapy may paradoxically increase the likelihood of septic shock and other complications: endotoxin or its constituent lipopolysaccharide fragments from the walls of killed bacterial cells may be mediators for septic shock, possibly by leading to enhanced levels of tumour necrosis factor (TNF), particularly TNF.alpha.. It is to the problem of treating or preventing septic shock and other life-threatening inflammatory conditions that the present invention is addressed.
It has been discovered that a group of muramyl peptide compounds is useful in treating or preventing progressive septicaemia and septic shock. Certain muramyl dipeptides (MDPs) have previously been disclosed as having immunopotentiating,
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Chan Christina Y.
Peptech (UK) Limited
Prickril Benet
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