Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1996-04-02
2000-07-18
Witz, Jean C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 8, 530380, 530417, A61K 3816
Patent
active
060907770
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention is in the field of immunology/cardiology/biochemistry, and describes more particularly a method to reduce myocardial cell injury during acute myocardial infarction.
BACKGROUND OF THE INVENTION
Mechanical failure of heart muscle is one of the leading causes of in-hospital deaths in patients with acute myocardial infarction (AMI). Friedberg C. K., 1968, Circulation 39 suppl. IV: 252. An important determinant in the development of such failure is the amount of necrotic tissue in the jeopardized myocardium. Pare D. L. et al., 1971, New Eng J Med 285: 133. Experimental studies in animals have shown that irreversible myocardial cell injury starts about 30 minutes after occlusion of coronary vessels and proceeds for hours. Maroko P. R. et al., 1973, Ann Int Med 79: 720. However, even interventions given as late as 6 hours after cornary occlusion are able to reduce infarction size after AMI by about 35% compared to untreated control animals. Libby P. et al., 1973, J Clin Invest 52: 599. Electro-cardiographic studies indicate that also in humans a substantial amount of myocardial tissue may not become irreversibly injured until hours or even days after occlusion of the coronary vessel, i.e. at a time that most patients will have been admitted to a hospital. Reid P. R. et al., 1974, New Engl J Med 290: 123. A number of experimental and clinical studies have attempted to minimize infarction size by reducing the myocardial necrosis that occurs in the later stages of AMI. Maroko P. R. et al., 1973, Ann Int Med 79: 720.
The later phase of myocardial cell injury likely results from an ensuing acute inflammatory reaction characterized by infiltration of neutrophilic granulocytes (neutrophils). Entman M. L. et al., 1991, FASEB J 5: 2529. Initially, the importance of an inflammatory reaction in mediating myocardial cell injury during AMI was recognized in animal studies which showed that corticosteroids could reduce infarction size by 20 to 35%. Libby P. et al., 1973, J Clin Invest 52: 599;Maclean D. et al., 1978, J Clin Invest 61: 541. However, clinical application of methyl-prednisolone in AMI to minimize myocardial necrosis, was not successful mainly because this treatment interfered with scar formation and healing, leading in some patients to the development of aneurysm and rupture of the ventricle wall. Roberts R. et al., 1976, Circulation 53 Suppl. I: 204. A similar effect has been observed in long-term experiments in rats. Maclean D. et al., 1978, J Clin Invest 61: 541. These disappointing results tuned down further clinical studies that aimed at reducing infarction size by attenuating the inflammatory reaction following AMI.
The inflammatory reaction which occurs in the course of AMI comprises some important events: the local production of chemotactic factors, the infiltration and activation of neutrophils, the local production of cytokines (such as tumor necrosis factor-.alpha. and interleukin-6) to enhance adherence of neutrophils to cardiac myocytes, and the local activation of the complement system. Entman M. L. et al., 1991, FASEB J 5: 2529.
A role of complement activation in AMI was initially suggested by Hill and Ward who provided evidence that complement activation products generated in the infarcted myocardium were responsible for the infiltration of neutrophils. Hill J. H. et al., 1970, J Exp Med 131: 885. Later studies showed that plasma levels of activated complement components are increased in patients with AMI and that several complement components become localized in the infarcted area during the course of AMI, as has been demonstrated both in animals as well as in patients. Pinckard R. N. et al., 1975, J Clin Invest 56: 740; Langlois P. F. et al., 1988, Atherosclerosis 70: 95; Yasuda M. et al., 1990, Circulation 81: 156; Pinckard R. N. et al., 1980, J Clin Invest 66: 1050; McManus L. M. et al., 1983, Lab Invest 48: 436; Schafer H. et al., 1986, J Immunol 137: 1945; Hugo F. et al., 1990, Clin Exp Immunol 81: 132.
Furthermore, a number of studies have demonstra
REFERENCES:
patent: 4915945 (1990-04-01), Pelzer et al.
Reyes et al., Arch Inst Cardiol Mex 54(4): 327-332 (1984). Abstract.
Gardinali et al., Bollettino Dell Instituto Sieroterapico Milanese 61(1): 1-7 (Mar. 1982). Abstract, Feb. 1982.
Werns et al., Cardiovascular Drugs & Therapy 2(6): 761-769 (Jan. 1989). Abstract.
Langlois et al., Atherosclerosis 70: 95-105 (1988).
Guerrero et al., J. Clin. Invest. 91(6): 27542760 (Jun. 1993).
Engelberg, American Heart Journal 99(3): 359-372 (Mar. 1980).
Hack Cornelis Erik
Hermens Willem Theodoor
Stiching Centraal Laboratorium Van de Bloedtransfusiedienst Van
Witz Jean C.
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