Drug – bio-affecting and body treating compositions – Inorganic active ingredient containing – Heavy metal or compound thereof
Patent
1993-08-26
1996-04-30
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Inorganic active ingredient containing
Heavy metal or compound thereof
424650, 423606, 423618, 423593, A61K 3324, C01G 3900
Patent
active
055123058
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of G1391/02101 Nov. 27, 1991.
This invention concerns improvements in chemical compounds, more especially it concerns compounds and pharmaceutical compositions. In particular it concerns compositions and compounds having activity in in vitro tests on Human Immunodeficiency Virus-infected cells.
The disease known as Acquired Immune Deficiency Syndrome (AIDS) caused by infection by HIV has attracted immense research effort because of the effects of the disease on infected individuals and the dangers of the disease spreading to a wider section of the population. In general, although various chemo-therapeutic treatments have been advocated, and some compounds have emerged as a potential basis for treatment, there is still a need for alternatives. In particular, most treatments such as the compound known as AZT have a high toxicity to cells, and it would be desirable to find compounds which are less toxic. In man, the development of resistance to AZT has been identified as an additional clinical problem.
We have found certain compounds which show protective properties in in vitro screens of cells challenged with HIV-1 and/or HIV-2, and are therefore indicated as having potential for the treatment of AIDS and AIDS Related Complex and other vital and especially retroviral infections. Accordingly, the present invention provides the use of compounds defined below, in pharmaceutical compositions for treating HIV-infected patients. The invention further provides pharmaceutical compositions comprising a said compound in combination or association with a pharmaceutically acceptable diluent or excipient, for the treatment of HIV-infected patients. The invention may also be defined as the use of a said compound for the manufacture of a medicament for the treatment of HIV-infected patients. The invention further provides a process for the production of a pharmaceutical composition for the treatment of a HIV-infected patient, comprising the combination of a compound as defined below with a pharmaceutically acceptable diluent or excipient, and formulating said composition into a form suitable for administration to said patient. The invention also provides a method of treatment of an HIV-infected patient, comprising administering to said patient an effective dose of a said compound. It is to be understood that treatment includes prophylactic treatment of patients at risk, in view of the protective properties observed. Whilst this description is especially directed to combating HIV, this invention includes other aspects in which other diseases may be treated, including for example microbial infections.
It has been suggested, in JP 64-38,022, that certain salts of heteropolyacid ions of general formula (XM.sub.12 O.sub.40).sup.p- where X is an ion selected from Groups III to VI or transition metal, M is one to three species selected from Mo, W, Al, V, Nb, Ta, Co and Ti, and P is a positive integer, exemplified by the two compounds K.sub.5 BW.sub.12 O.sub.40 and K.sub.7 PW.sub.10 Ti.sub.2 O.sub.40 which have activity against herpes virus, could be expected to have activity against human retrovirus.
It has also been reported in Chemical and Engineering News, December 1986, that silicotungstate acid, H.sub.4 SiW.sub.12 O.sub.40 has activity against HIV; this compound has, however, been abandoned because of its toxicity in higher animals.
We have now discovered certain polyoxotungstoniobates of different type from those previously described, which exhibit very significant activity in conventional in vitro screening trials. Accordingly, the present invention provides as active compound, a compound selected from those containing ions of the following general formula:
For the purposes of the present invention, preferred ions are those in which element A is selected from one or more of H, P, Ge and Si. Preferably, when x=0, y=6-a, a is an integer from 1 to 5 and b=19; when A=Si or Ge, x=2, y=18, a=6 and b=77, and when A=P, x=2 or 4, y=12, 15, 17 or 30, a=1, 3 or 6 and b=62 or 123. The skilled man will readily
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Abrams Michael J.
Bossard Gerald E.
Hill Craig L.
Schinazi Raymond F.
Theobald Brian R. C.
Lambkin Deborah
Raymond Richard L.
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