Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1996-05-21
1998-12-08
Fay, Zohren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
514530, A61K 3166, A61K 31215
Patent
active
058469575
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/SE94/01091 filed on Nov. 181, 1994.
The present invention relates to the use of an ester of inositoltrisphosphate for the preparing of a medicament effective against retroviral diseases.
Acquired immunodeficiency syndrome (AIDS) is a serious immunodeficiency disease induced by human immunodeficiency virus (HIV), type 1 and type 2 (HIV-1 and HIV-2). HIV, which is the aetiological agent for AIDS is a nononcogenic, cytopathic retrovirus of the lentivirus subfamily. Retro-viruses have their genetic material in the form of RNA, ribonucleic acid, instead of DNA, deoxyribonucleic acid. In order to turn their RNA into DNA, retroviruses have a special enzyme called reverse transcriptase.
The HIV-virus, 100 nm in diameter is covered by an envelope, and contains a surface glycoprotein as well as an internal cylindrical core. The envelope is formed by phospholipids and glycoproteins and the core contains the genome and several enzymes.
HIV infects human cells primarily by binding to CD4 receptors on the surface of susceptible cells. This binding is mediated by the oligomeric envelope glycoprotein (gp) of HIV and the receptor on the target cell surface followed by the fusion between the viral envelope and the plasma membrane. The post-binding events which lead to membrane fusion are poorly understood but presumably include a conformational change in the envelope protein which exposes the hydrophopic amino terminus of a gp 41 envelope protein in the fusion reaction.
The binding of the HIV-1 envelope glycoprotein, gp 120, to the cellular receptor is the first step in HIV infection. However, there is also evidence for CD4 independent mechanism of infection. There are reports of HIV infection in a number of CD4-negative cells in vitro (Harouse, J. M. et al., J. Virol, 63, 2527, 1989, Zachar, V. B. et al. J. Virol, 65, 2102, 1991).
These data show that the expression of CD4 alone is not absolute obligatory and not sufficient to support HIV infection and implies that there are other molecules required for infection.
The patophysiological basis of the profound and irreversible immune depression following the infection is obscure.
AIDS was first recognized in 1981 in young, homosexual men from the U.S. with opportunistic infections, Kaposi's sarcoma, and primary CNS lymphoma. Although unusual cases of systemic malignant lymphoma were also recognised at that time, statistically significant increases were not apparent until 1985. Victims also suffered from other opportunistic infections, caused by microorganisms that are ubiquitous but ordinarily not able to cause disease. Indeed, the infections and cancers seen in AIDS patients were previously known only in people born with certain defects in their immune system.
Since the disease was first recognised the number of cases have risen swiftly. According to the World Health Organisation the increase of AIDS will result in up to 40 million people infected with HIV by the year 2000.
Recently the HIV infection has been classified into three distinct stages: the acute phase, lasting weeks, the chronic phase, lasting years, and the final phase of crisis (generally referred to as AIDS) lasting months to years.
AIDS is an unique disease. No other known infectious disease causes comparable harm by directly attacking the human immune system.
Once in the human body the virus attacks the cells that usually defend the body against infectious diseases. These cells include monocytes, macrophages and dendritic cells, so called antigen presenting cells (APC). Furthermore HIV can remain hidden in cells latent for months or years. A third difficulty is that HIV is extraordinary variable in its genetic make-up.
In 1985, zidovudine (AZT) was found to have in vitro activity against the human immunodeficiency virus, HIV. The in vitro and clinical activity of zidovudine is not disputed, but there is considerable debate when to initiate treatment (J. G. Bartlett,: New Engl. J. of Med., 329, 351, 1993; Cooper D. A. et al.: New Engl. J. of Med., 329, 297, 1993).
AZT can have
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Fay Zohren
Perstorp AB
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