Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1995-05-16
1998-09-01
Travers, Russell
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 31, A61K 3800, A61K 3170
Patent
active
058011447
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
The present invention relates to the use of a compound for the manufacture of medicament for the treatment of Human Immunodeficiency Virus (HIV) infection.
Infection by HIV, of which there are two distinct types HIV-1 and HIV-2, leads to the development of Acquired Immune Deficiency Syndrome (AIDS).sup.1,2. Several compounds which interfere with the replication of the virus have been developed for the treatment of AIDS, however only one compound, AZT (Azidothymidine), has been widely used in the treatment of HIV infection.
Although AZT is a highly effective drug in blocking HIV replication, it has two major drawbacks. Firstly, it is frequently toxic inhibiting not only HIV replication but also the division of bone marrow cells causing anaemia, leukopenia, neutropenia and thrombocytopenia.sup.3,4. Secondly, within six months of prolonged treatment, AZT-resistant mutants of HIV appear.sup.5.
Thus, there is an urgent need to find drugs that will interfere with HIV replication without overt cytotoxicity. It is known that HIV replication depends on T-cell activation and proliferation.
The aim of the present invention is to develop an agent which inhibits HIV replication. It was thought that if T-cell activation could be suppressed, HIV replication would be inhibited.
This aim is achieved by affecting the signal transduction pathway for T-cell activation by administering calcineurin-antagonists and/or rotamase-antagonists and/or NF-AT-antagonists.
Accordingly the present invention provides the use of calcineurin-antagonists for the manufacture of a medicament for the treatment of HIV infection.
In another aspect, the present invention provides the use of rotamase-antagonists for the manufacture of a medicament for the treatment of HIV infection.
In a further aspect, the present invention provides the use of NF-AT-antagonists for the manufacture of a medicament for the treatment of HIV infection.
Suitable for use according to the present invention are compounds that act as calcineurin-antagonists, rotamase-antagonists or NF-AT-antagonists, for example 4-dimethyl-L-threonyl!-L-homoalanyl-(N-methylglycyl)-(N-methyl-L- leucyl)-L-valyl-(N-methyl-L-leucyl)-L-alanyl-D-alanyl-(N-methyl-L-leucyl)- (N-methyl-L-leucyl)-(N-methyl-L-valyl)}) and !octacos-18-ene-2,3,10,16-tetrone)
Also included within the scope of the invention are medicaments for the treatment of HIV infection which comprise a compound of the invention as active ingredient in association with a pharmaceutically acceptable carrier or diluent.
The medicament of the invention will normally be administered orally or by injection.
Compositions for parenteral administration will normally be solutions in aqueous saline, which is pyrogen free for human use. Such compositions can be administered intravenously or intraperitoneally.
Compositions for oral administration will mostly be in solid or liquid form, mostly as tablets, capsules, lozenges, etc. Liquid compositions can be solutions or dispersions in aqueous or non-aqueous media. Ideal solutions are of neutral or alkaline pH and of low ionic strength, e.g 5% dextrose.
Suitable daily doses of the antagonists when used in accordance with the invention range from about 10 mg to 1 g/m.sup.2 body surface.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1: Cytotoxicity and anti-HIV activity of the drugs.
FIG. 2A: Effect of the drugs on the growth of non-infected cells. Open triangle, control cells grown in the presence of growth medium only; closed triangle, cells grown in the presence of 4 .mu.g/ml CsA; open circle, cells grown in the presence of 10 .mu.g/ml CsA; closed circle, cells grown in the presence of 4 .mu.g/ml FK506; and, open square, cells grown in the presence of 10 .mu.g/ml FK506.
FIG. 2B: Effect of the drugs on the growth of chronically infected cells. Open triangle, control cells grown in the presence of growth medium only; closed triangle, cells grown in the presence of 4 .mu.g/ml CsA; open circle, cells grown in the presence of 10 .mu.g/ml CsA; closed circle, cells grown in the presence of 4 .mu.
REFERENCES:
Douvas et al, 1791, PNAS, vol. 88 pp. 6328-6332.
Shirak, et al 117CA:14436 t 1992.
Wainberg et al 110CA:50931 g 1989.
Klatzman et al 106CA:27522 R 1987.
Hill Fergal
Karpas Abraham
LandOfFree
Use of a compound for the manufacture of a medicament for the tr does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of a compound for the manufacture of a medicament for the tr, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of a compound for the manufacture of a medicament for the tr will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-270241