Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Reexamination Certificate
2001-06-22
2004-02-24
Lambkin, Deborah (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
Reexamination Certificate
active
06696427
ABSTRACT:
This invention relates to the inactivation of &ggr;&dgr;-T cells, inter alia by the use of bisphosphonates for the therapeutic and prophylactic treatment of infections in humans and animals which are caused by viruses, bacteria, fungi and parasites.
The use of bisphosphonic acids and some of the derivatives thereof in pharmaceutical preparations is already known. The microbiostatic activity of bisphosphonic acids (DE 3 611 522), their activity in the treatment of disorders of calcium and phosphate metabolism (DE 2 534 390, DE 2 534 391, DE 3 334 211, DE 3 434 667, DE 2 745 083), their cytostatic activity (DE 3 425 812), their lipid-reducing activity (Arzneimittelforschung 46, 759-62) and their ability to stimulate immune cells WO 97/38 696) are already known.
In order to widen the range of options for treating humans and animals, there is an urgent requirement to provide agents which are highly active.
The object of the present invention is accordingly to provide a substance which is universally usable in infections by viruses, bacteria, fungi and parasites in humans and animals and which meets the above-stated requirements.
This object is utterly surprisingly achieved by the group of substances defined in claim 2. This group of substances exhibits antiinfective action against viruses, bacteria, fungi, uni- and multicellular parasites.
The immune system protects humans and animals from tumours, infections etc. When the body is confronted with an immunogen (for example constituents of a microorganism), this brings about the multiplication and maturation of cells which are capable of combating this immunogen. Only one part of the immune system effects the actual specific immune response, with a second regulatory part providing assistance. Immunosuppression is a function of the regulatory components. These cells prevent the immune reaction from exceeding certain limits. Certain T cell populations, such as the &ggr;&dgr;-T cells, are able to effect this immunosuppression (McMenamin et al., Science Sep. 23, 1994; 265(5180): 1869-71). These cells are stimulated by various microorganisms (Jomaa et al. FEMS Immunol. Med. Microbiol. September 1999; 25(4); 371-8). This group of pathogens includes
Plasmodium falciparum
, the causative organism of malaria,
Mycobacterium tuberculosis
, the causative organism of
tuberculosis
, and the Epstein-Barr virus, the causative organism of mononucleosis. These pathogens hold the immune system in check by simulating immunosuppressive &ggr;&dgr;-T cells, which means that no proper immune defence comes into effect. As a result, the microorganisms are able to exist in the host and persist for a very long time.
It has now been found that substances of the general formula (I)
in which
A
1
, A
2
, A
3
, A
4
, which may be identical or different, are selected from the group which consists of hydrogen, metals of main groups I, II and III of the periodic system, such as Na, K, Ca, Mg, Al as well as substituted and unsubstituted ammonium and ammonium compounds derived from ethylenediamine or amino acids,
X is absent or is selected from the group which consists of alkylene with up to 9 carbon atoms, alkenylene with up to 9 carbon atoms, hydroxyalkylene with up to 9 carbon atoms and amidino,
R
1
is selected from the group which consists of H, OH, NH
2
, —CH
3
,
R
2
is selected from the group which consists of H, OH, —NH
2
, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic residue and the pharmaceutically compatible salts, amides, esters and salts of the esters or compounds which, on administration, form the compounds to be administered as metabolites or breakdown products,
result in inactivation of the &ggr;&dgr;-T cells in humans and animals. These substances are accordingly suitable for the treatment and prophylaxis of infectious diseases caused by parasites, bacteria and viruses. In particular, these substances are suitable for the eradication of persistent infectious organisms including
Helicobacter pylori
, Chlamydia and hepatitis C virus.
These substances are furthermore suitable as an adjuvant to vaccines to strengthen the immune response to vaccinations.
Preferably suitable substances of the formula (I) are those in which
A
1
, A
2
, A
3
, A
4
, which may be identical or different, are selected from the group which consists of hydrogen, metals of main groups I, II and III of the periodic system, such as Na, K, Ca, Mg, Al, substituted and unsubstituted ammonium and ammonium compounds derived from ethylenediamine or amino acids,
X is absent or is selected from the group which consists of alkyl, (CH
2
)
1-6
, in particular (CH
2
)
1-5
, and amidino,
R
1
is selected from the group which consists of H, OH, NH
2
, —CH
3
, and
R
2
is selected from the group which consists of
Special features of the above definitions and suitable examples thereof are given below:
“Acyl” is a substituent which originates from an acid, such as from an organic carboxylic acid, carbonic acid, carbamic acid or the thio acid or imidic acid corresponding to the above individual acids, or from an organic sulfonic acid, wherein these acids in each case comprise aliphatic, aromatic and/or heterocyclic groups in the molecule together with carbamoyl or carbarmimidoyl.
Suitable examples of these acyl groups are given below.
Aliphatic acyl groups are defined as acyl residues originating from an aliphatic acid and include the following:
alkanoyl (for example formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl etc.); alkenoyl (for example acryloyl, methacryloyl, crotonoyl etc.); alkylthioalkanoyl (for example methylthioacetyl, ethylthioacetyl etc.); alkanesulfonyl (for example mesyl, ethanesulfonyl, propanesulfonyl etc.); alkoxycarbonyl (for example methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl etc.); alkylcarbamoyl (for example methylcarbamoyl etc.); (N-alkyl)thiocarbamoyl (for example (N-methyl)thiocarbamoyl etc.); alkylcarbamimidoyl (for example methylcarbamimidoyl etc.); oxalo; alkoxalyl (for example methoxalyl, ethoxalyl, propoxalyl etc.).
In the above examples of aliphatic acyl groups, the aliphatic hydrocarbon moiety, in particular the alkyl group or alkane residue, may optionally have one or more suitable substituents, such as amino, halogen (for example fluorine, chlorine, bromine etc.), hydroxy, hydroxyimino, carboxy, alkoxy (for example methoxy, ethoxy, propoxy etc.), alkoxycarbonyl, acylamino (for example benzyloxycarbonylamino etc.), acyloxy (for example acetoxy, benzoyloxy etc.) and the like; preferred aliphatic acyl residues with such substituents which may be mentioned are, for example, alkanoyls substituted with amino, carboxy, amino and carboxy, halogen, acylamino or the like.
Aromatic acyl residues are defined as those acyl residues which originate from an acid with a substituted or unsubstituted aryl group, wherein the aryl group may comprise phenyl, tolyl, xylyl, naphthyl and the like; suitable examples are stated below:
aroyl (for example benzoyl, toluoyl, xyloyl, naphthoyl, phthaloyl etc.); aralkanoyl (for example phenylacetyl etc.); aralkenoyl (for example cinnamoyl etc.); aryloxyalkanoyl (for example phenoxyacetyl etc.); arylthioaikanoyl (for example phenylthioacetyl etc.); arylaminoalkanoyl (for example N-phenylglycyl, etc.); arenesulfonyl (for example benzenesulfonyl, tosyl or toluenesulfonyl, naphthalenesulfonyl etc.); aryloxycarbonyl (for example phenoxycarbonyl, naphthyloxycarbonyl etc.); aralkoxycarbonyl (for example benzyloxycarbonyl etc.); arylcarbamoyl (for example phenylcarbamoyl, naphthylcarbamoyl etc.); arylglyoxyloyl (for example phenylglyoxyloyl etc.).
In the above-stated Examples of aromatic acyl residues, the aromatic hydrocarbon moiety (in particular the aryl residue) and/or the aliphatic hydrocarbon moiety (in particular the alkane residue) may optionally have one or more suitabl
Harness & Dickey & Pierce P.L.C.
Jomaa Pharmaka GmbH
Lambkin Deborah
LandOfFree
Use of bisphosphonates for the prevention and treatment of... 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 bisphosphonates for the prevention and treatment of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of bisphosphonates for the prevention and treatment of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3351947