CA2334645A1 - Combined preparation of anti-infectiously active compounds which inhibit the 2-c-methylerythrose-4 metabolic pathway, and inhibitors of lipid metabolism - Google Patents

Abstract

The invention relates to a combined preparation which, as an active ingredient, contains at least one anti-infectiously active compound that inhibits the 2-C-methylerythrose-4 metabolic pathway, and which contains at least one lipid metabolism inhibitor. The combined preparation is used in infectious processes, especially in infections in humans and animals and as a herbicide in plants. It is shown that the build-up of resistance against the inventive combined preparation is largely reduced compared to the build-up o f resistance against the individual components.

Description

Combined preparation of anti-infectiousl~active comt~ounds which inhibit the 2-C
methylerythrose-4 metabolic pathway. and inhibitors of lipid metabolism The invention relates to combined preparations of anti-infectiously active compounds which inhibit the 2-C-methylerythrose-4 metabolic pathway as well as their salts and esters and of inhibitors of lipid metabolism and their simultaneous, separate or successive use in prophy-lactics and therapy of infectious processes in plants, humans, and animals as well as their use as herbicides. The lipid metabolism inhibitors according to the present invention suit in par-ticular for the therapeutic and prophylactic treatment of infections by unicellular or multicel-lular parasites, fungi, bacteria or viruses as well as as herbicides.
The suitability of different organophosphoric compounds as well as of some of their esters and salts as pharmaceutical compositions is already known.
For example the antimicrobial efficacy of aminc'rydrocarbyl phosphoric acid derivatives against bacteria in humans and animals and against fungi in plants has been described (DE 27 33 658 A1, US 4,143, I35, US 4.182,758 and US 4,206,156, US 4,994,447, US
4,888,330, US
4,210,635, US 3,955,958, US 4,196,193, US 4,268,503, US 4,330,529, US
5,189,030, US
3,764,677, US 3,764,676). Further substances ofthese groups have been described as herbi-cides (US 4,693,742, US 5,002,602, US 4,131,448, US 3,977,860, US 4,062,669), as algicides (US 3,887,353), as plant growth regulators (US 4,127,401, US 4,120,688, US
3,961,934, US
4,431,438, US 3,853,530, US 4,205,977, US 4,025,332, US 3,894,861) and as reagents in the production of pigments (US 4,051,175).
The application for example of am.inohydrocarbyl phosphoric acid derivatives in the control of bacterial infections proved to bf; very difficult. Many bacteria which are responsible for ambulant infections and for infections which have been caught during a clinical stay are not sensitive to therapy by this group. Bacteria of the genus Staphylococcus belong to them, in particular the species Staphylococcus aureus. This germ of skin is a danger for the patient who stay in a clinic. Further studies including a phase IIa study of the applicant of the patent application DE 27 33 658 show a very quick built-up of resistance of the originally sensitive germs. Therefore these derivatives. have not established in clinical application.
Further, also the use of bisphosphonic acids and some of their derivatives in pharmaceutical compositions is already known. U~p to now, the microbiostatic efficacy of bisphosphonic acids (DE 3 611 522), their efficacy in the treatment of disorders in the calcium and phosphate metabolic pathway (DE 2 534 390, DE 2 534 391, DE 3 334 211, DE 3 434 667, DE

083), the cytostatic efficacy (DE 3 425 812), their lipid lowering efficacy (Arzneimittelfor-schung 46, 759-62) and their capacity for stimulating immuncompetent cells (WO
97/38 696) is known.
The antimicrobial efficacy of fosfonochlorine against bacteria and an effect of foscannet against viruses have been described. Further, the suitability of fosamine ammonium and N,N-dimethyl-(hydroxy-2-oxo-2-methoxyethyl) phosphonoamide as herbicides have been re-ported.
The use of inhibitors of the lipid metabolism is a for a longer time past accepted and wide-spread principle of treatment. These inhibitors are used for reducing the risk of heart and vas-cular diseases caused by hyperlipiclaemia. The pharmacotherapy of said hyperlipidaemia in general is based on regulating the intake and controlling the synthesis of fats or in particular of cholesterol. Generally the synthesis of cholesterol is controlled by enzyme ~i-hydroxy-methylglutaryl-CoA reductase (IWG-CoA reductase). In general the self synthesis of choles-terol is higher than the intake by food. (Berthold H.K., of Bergmann K., Dtsch. Med. Wo-chenschr.12' , 5.729 (1996); RichtE;r W.O., Fortschr. med. 114, S. 177, ? ~~) Anion exchangers and (3-sitosterol are known for controlling the intake of fats from the diges-tive tract. The ion exchangers contain cholestyr amine and colestipol. They resort bile acids and thereby interrupt the entero hepatic return transportation and thereby cause a significant increase of sterolene in faeces. (3-Sitosterol is a phytogenic sterol structurally related to cho-lesterol. It inhibits the resorption oiF food cholesterol at the intestinmucosa.
Further, nicotinic acids and their derivatives, clofibrate and their derivatives and probucol have been used for controlling the llipid metabolism or the prevention of subsetluent diseases of hyperlipidaemia. Nicotinic acids, and nicotinic acid derivatives lead to a lowering of fatty acids, triglyceride and cholesterol. Up to now the mechanism is not known. The ethyl ester of clofibrin acid, clofibrate and derivatives as well as analogues lead to a lowering of choles-terol, the mechanism of action is also not known. Also the mechanism of action of probucol is not clarified.
For controlling the synthesis HMG-CoA synthetase inhibitors (US 50 64 856, US
47 51 237), HMG-CoA reductase inhibitors (US 38 18 080, US 39 83 140, US 40 49 495, US 41 :37 322, US 42 55 444, US 41 98 425, US 42 62 013, US 42 31 938, US 43 75 475, US 43 46 227,US
44 106 29, US 44 447 84, US 44 50 171, US 45 54 359, US'49 201 09, EP
0065835A1, EP
0142146A2, GB 15 86 152, US 33 75 475, GB 21 62 179A, EP 164698A, WO 8402903, WO
8401231, WO 8603488A US 46 81 893, US 46 45 858, US 52 36 946, US 55 06 262, 25 017, US 48 47 271, US 46 22 338, US 49 04 646, US 48 73 345, US 55 93 971, 305, US 52 02 327, US 49 40 727, US 52 72 166, US 53 85 932, US 54 61 039, US

990, US 55 61 143, US 55 63 128), inhibitors of squalene synthetase, in particular pyrophos-phates, pyrophosphate derivatives, bisphosphonic acid derivatives, phosphinylmethylphos-phonic acid derivatives, phosphinylformyl derivatives, phosphonocarboxyl derivatives, phos-phonosulfonic acid derivatives, phosphinylmethylphosphonic acid derivatives, which partly are known as pharmaceutical and cosmetic preparations for controlling the calcium and phos-phate metabolism (DE 25 34 390, DE 25 34 391, DE 33 34 211, DE 34 34 667, DE

083, US 53 12 814, US 52 54 544, US 54 70 845, US 50 25 003, US 55 34 532, US

721, WO 92 15 579, US 51 35 935, WO 92 12 160, WO 92 12 159, WO 92 12 158, WO

12 157, WO 92 12 156, US 52 73 969, US 53 95 846, US 54 41 946, US 54 51 596, 260, US 55 63 128, US 52 02 327, US 49 04 646), and other inhibitors of the synthesis of cholesterol (US 56 61 145, US 57 44 467) are used which assignment is not clarified. HMG-CoA reductase inhibitors competitively inhibit the rate of controlling enzyme of the synthesis of cholesterol, HMG-CoA reductase. Their enzyme affinity is up to 20000-times higher than that of substrate HMG-CoA. The >-1MG-CoA reductase results in transformation of HMG-CoA to mevalonate, from which besides cholesterol inter alia isopentenyl adenine as well as farnesyl pyroph~~?hate, the preliminary stage of dolichol and ubiquinone, c~~inate. In bacte-ria, fungi and parasites which have a HMG-CoA reductase isopentenyl diphosphates are gen-erated upon the acetate/mevalonate pathway, which is inhibited by HMG-CoA
reductase in-hibitors.
The first discovered inhibitors have: been isolated from a penicillium (mevastatin) and an as-pergillus fungi (lovastatin). The modification of the side chain led to simvastatin, the ad-vancement of mevastatin to pravastatin. Meanwhile also a completely synthetic enzyme in-hibitor (fluvastatin) is available representing a mevalonic lactone derivative of a fluorophenyl substituted indole ring.
In the past attempts for use of these substances in the control of infectious diseases have been made. In particular attempts have been made to inhibit the growth of plants, fungi, parasites, bacteria and viruses by the use of WIG-CoA inhibitors. The HMG-CoA synthetase and HMG-CoA reductase inhibitors inhibit the acetate/mevalonate pathway in some bacteria, fungi (US 50 26 554, US 50 64 856, US 49 20 111, US 49 20 113) and parasites.
However many bacteria, for example Escherichia coli, do not show inhibition by HMG-CoA
reductase inhibitors. Probably the reason is that these bacteria have an alternative metabolic pathway. In Escherichia coli indeed the absence of the acetate/mevalonate metabolic pathway and the presence of another metabolic pathway has been proved {Roh.mer M. et al., Biochem.J. 295, S.517( 1993); Lois E.M. et al., Proc. Natl. Acad. Sci. USA 95, 5.2105 (1998)).
For parasites up to now no alternative metabolic pathway has been known. The applicant of the present invention succeeded in proving an alternative metabolic pathway, the so-called 1-deoxyxylulose-5-phosphate or 2-C-~methylerythrose-4-phosphate pathway for parasites.
Studies of HMG-CoA-reductase inhibitors in pxasites resulted in different results in depend-ence on the parasites. For example ;pathogens of schistosomiasis are not killed by high doses of lovastatin, while pathogens of malaria are killed in vitro, but not in vivo. Also the patho-gens of sleeping sickness are not fully inhibited by inhibitors of HMG-CoA
reductase.. Similar attempts in inhibiting the increase of viruses show that cells infected by viruses loose the in-hibiting influence of the HMG-CoA reductase inhibitors.
Also squalene synthetase inhibitors, such as the aminobisphosphonate, have been examined without success as inhibitors of the amoebic dysentery. A low efficiency of killing has been shown. Similar experiments with toxoplasm also show no satisfying results.
Further also in-hibitors of squalene monooxygenase have been developed as fungicides (US 47 82 059).
It is therefore an object of the present invention to provide agents, which may be used against infectious processes in humans, animals and plants and as herbicides and against which the built-up of resistance i- ~lants, viruses, fungi, parasites and bacteria is significantl; ~Pduced.
Surprisingly, it has been found that the combination of anti-infectiously active compounds, which inhibit the 2-C-methylerythrose-4 metabolic pathway, and inhibitors of the lipid syn-thesis, in particular the synthesis of cholesterol, in particular of inhibitors of HMG-CoA re-ductase, and the squalene synthetase increase the scope and the effectiveness of therapy and prophylactics of infections. Surprisingly, the combination kills microorganism, which are killed neither by the first nor by the second group. Surprisingly the combinations show a sig-nificant reduction of build-up of resistance against the used compounds, which is generally the major problem in handling the compound group of lipid metabolism inhibitors.
Lipid metabolism inhibitors of anti-~infectiously active compounds, which inhibit the 2-C-methylerythrose-4 metabolic pathway, and inhibitors of the lipid metabolism are suited for the therapeutic and prophylactic treatment of infections in plants, in particular in humans and animals, in particular of infections, which are caused by parasites, bacteria, fungi and viruses, and as herbicides in plants.
Lipid metabolism inhibitors according to the invention contain at least one anti-infectiously active compound, which inhibits the 2-C-methylerythrose-4 metabolic pathway and/or their esters and/or their salts. Generally, ;pharmaceutically acceptable salts, esters, salts of esters or compounds which upon application provide compounds according to the invention as meta-bolic products or decomposition products, also called "prodrugs", are included.
In the following some groups of substances are described by example which show excellent success in therapy and prophylactic treatment of infections in combination with lipid metabo-lism inhibitors.
The groups of anti-infectiously active substances may be determined by a method, in which the proteins being part of the 2-C-methylerythrose-4 mefiabolic pathway or their derivatives are contacted with the active agents to be examined, and the active agents inhibiting the pro-teins or derivatives are selected. The method is known by a person skilled in the art.
I. Combined preparations of lipid metabolise inhibitors and aminohydrocarbyl phos-phoric acid derivatives The aminohydrocarbyl phosphoric acid derivatives as well as their preparation have been described in DE-Al-2733658 and the PCT/EP99/02462 in detail.
The aminohydrocarbyl phosphoric acid derivatives correspond to the general formula (I):
RI, 0 \ II
N-AI-P-RIS ( T ) I
Rz2 R_=
in which RIl and R~ may be the same or different and are selected from the group which con-sists of H, OH, substituted and unsubstituted aryl, substituted and unsubstituted alkyl, substi-tuted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsub-stituted aralkyl, and substituted and unsubstituted heterocyclic radicals, RI3 and RI4 are selected from the group which consists of substituted and unsubstituted allryl with 1 to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl with 1 to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl with 1 to 26 carbon atoms, sub-stituted and unsubstituted alkynyl with 1 to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, halogen, X~
and XI~, XI3 and XI4 may be the same or different and are selected from the group which consists of hydrogen, substituted and unsubstit~ted alkyl with 1 to 26 carbon atoms, substituted and un-substituted hydroxyalkyl with 1 to :26 carbon atoms, substituted and unsubstituted aryl, sub-stituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl with I to 26 carbon atoms, substituted and unsubstituted alkynyl with 1 to 26 carbon atoms, substituted and un-substituted cycloalkyl, substituted and unsubstituted heterocyclic radical, a silyl, a canon of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or anuno acids, and AI is an alkylene radical, alkenylene radical or hydroxy alkylene radical or corresponds to the following formula (IA):

I I I I I
'CI1'CI2'CI3'CI4'CI5' ~ IA) I I I I I
BI2 BI4 BI6 $I8 BI10 wherein one or more carbon atoms, selected from the group Cry, CIA, Cis, together with their substituents may also be absent, and at least one present substitute of B1 to Blo is a C~~-cycloalkyl-(Co_9)-alkyl group, wherein the C3_g-cycloalkyl group as well as the Co_9-alkyl group may comprise one or more double bonds and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms, and wherein the cycloalkyl group as well as the alkyl group may be substituted with hydroxy, halogen, amino, oxo groups with branched or straight C1_9-alkyl groups and Cz_9-alkenyl groups, wherein the Ci_9-alkyl groups and Cz_9-alkenyl groups may be substituted with hydrogen, hydroxy, amino, halogen and oxo groups, and the remaining present substituents BI1 to Biro are selected from the group which consists of hydrogen, hydroxy, halogen, amino groups, C1_zs-alkyl radicals, Ci_z6=alkoxy radi-cals, Ci_z6-alkoxy-Ci_z6-alkyl radicals or both substituems of one C-atom together form an oxo group, wherein each C,_z6-alkyl radical and each C1_z6-allcoxy radical may be branched or straight and saturated or unsaturated with one or more double bonds and may be substituted with hydroxy, amino, halogen and oxo groups.
According to the invention the inhibitor of lipid metabolism is not an aminohydrocarbyl phosphoric acid derivative of the formula (I) if an aminohydrocarbyl phosphoric acid deriva-tive is used as the anti-infectiously compound.
The invention also comprises the pharmaceutically acceptable salts, esters and salts of esters.
Preferably RIl is OXn, R~ is OX~, and RI4 is OXIa, wherein XIl is selected from the group which consists of hydrogen, substituted or unsubstituted aryl, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or un-substituted cycloalkyl or substituted or unsubstituted heterocyclic radical and R~z, Xr~, Xta and AI contain the same meaning as in formula (I).
Preferably the carbon chain of A, consists of three carbon atoms.
Compounds in which the carbon chain of AI of formula (IA) consists of four carbon atoms CIi, C~z, C~, CI4 and BIB or BIS or both are hydroxy groups are also preferred. In this case methylene groups are also preferred for R~ and RIa.

Preferably BIi and Bu together form furthermore an oxo group. In this case the carbon chain in AI consists of the four carbon atoms Cn, Cue, Cu, C14.
Preferably, BIB and BIg together form furthermore an oxo group. In this case the carbon chain in A also consists of four carbon atoms CII, Cu, Cu, CI4.
The carbon chain preferably consi5~ts of 5 carbon atoms Cil, Cu, Cu, CIA, CIS, wherein BIl and B~ together form an oxo group and at least one substituatt of B~ or Biro is a hydroxy group or BI9 and BI10 together also form an oxo group.
Also substances are suitable, in which a phosphoric acid or phosphinic acid or phosphinoyl group is replaced by a sulfonic group or sulfonyl group:

H
- S-RIB (IB) II

IL Combined preparations of lipid metabolism inhibitor and bisp6ospbonic acid derna-tives The bisphosphonic acids and their derivatives are described in detail in the simultaneously filed parallel International Patent application of the same applicant.
As bisphosphonic acids and their derivatives such of the general formula 0 RIIi 0 II I II
XII3O - p _ C _ P - OXIIi ( I I ) II I I
X_rlqO All OXII2 are used, wherein Xm, Xa2, Xm, Xn4 being the same or different are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted cycloalkyl, substituted and unsubsti-tuted heterocyclic radical, metals of the 1., 2. and 3. main group of the periodic systems, such as Na, K, Ca, Mg, A1 as well as substituted and unsubstituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids, An, which also may be absent, is selected from the group which consists of alkylene, alkenyl-ene and hydroxyalkylene, RIII, Riu, being the same or di$'erent, are selected from the group which consists of H, OH, --$_ NHz, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical and -SRm, Cl and lVRmRa~, wherein RII3, Rna being the same or different are selected from the group which consists of H, OH, substituted and unsubstituted aryl, substituted and unsubstituted alkyl, substituted and unsub-stituted aryl, substituted and unsub~stituted aralkyl, substituted and unsubstituted cycloallcyl and substituted and unsubstituted heterocyclic radicals, and their pharmaceutically acceptable salts, esters as well as salts of esters or compounds, which upon application provide the compounds to be administered as metabolic products or decom-position products.
Bisphosphonic acid derivatives of the formula II are particularly preferred in which Xal, X~, xII3~ Xna being the same or different are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl., substituted and uasubstituted aryl, substituted and unsub-stituted aralkyl, substituted and unsubst~~~ted cycloallcyl, substituted and unsubstituted het- -erocyclic radical, the metals of the 1., 2., or 3. main group of the periodic systems, such as Na, K, substituted and unsubstituted armmonium and ammonium compounds which derive from ethylene diamine or amino acids, Ati which also may be absent is selected from the group which consists of alkyl, (CHz)~, in particular (CH2)i-s and amidino, RII1 is selected from the group which consists of H, OH, NH2, -CH3, and RIB is selected from the group which consists of -NH2, -N , (CHZ)aCH3 N N
Bisphosphonates are particularly preferred, which are selected from the group which consists of amino hydroxy-methylidene-bisphosphonic acid, 2-amino-1-hydroxyethylidene-1,1-bisphosphonic acid, 3-amino-1-hydroxypropylidene-1,1-bisphosphonic acid, 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid, 6-amino-1-hydroxyhexylidene-1,1-bisphosphonic acid, amidino methylene bisphosphonic acid, 3-methylpentylamino-1-hydroxypropylidene-1,1-bisphosphonic acid, 2-(3-pyridinyl)-1-hydroxyethylidene-bisphosphonic acid, 1-hydroxy-2-(imidazole-1-yl)-ethylidene-1,1-bisphosphonic acid, cycloheptyl aminomethylene diphos-phonic acid, 4-chlorophenyl-thiom~ethylene-l,l-bisphosphonic acid as well as their deriva-tives.

If the anti-infectiously active compound is a bisphosphonic acid derivative, the lipid metabo-lism inhibitor is no bisphosphonic acid derivative.
III. Combined preparations of lipid metabolism inhibitor with organophosphorus com-pounds comprising a keto group These compounds are described in detail in the German Patent specification DE-637.2.
These compounds according to the invention correspond to the general formula {III):

il II
RI:=wAIIIiWz~.:m2-P-R=IIa ( I II ) I

in which Rlnl is selected from the group which consists of H, substituted and unsubstituted acyl, sub-stituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted .and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substi-tuted and unsubstituted heterocyclic radicals, halogen and OX~1, wherein Xiiii is selected from the l~oup which consists of hydrogen, substituted and unsub-stituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, a silyl, substituted and unsubstituted heterocyclic radicals, a cation of an organic and an inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds, RIa4 and R~3 may be the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsub-stituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralk:yl, substituted and unsubstituted heterocyclic radical, halo-gen and OXIa4 and OXIU3, wherein XcIia and X~ are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted cycloalkyl, a silyl, substituted and unsubstituted heterocyclic radical, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium - lU-compounds which derive from ethylene diamine or amino acids, and A~1 and AID, of which one or both may be absent are the same or different and represent an alkylene radical, alkenylene radical, an oxo radical, a hydroxy radical or oxo hydroxyalkylene radical, wherein A~ is preferably absent.
The invention comprises as well the pharmaceutically acceptable salts, amides, esters and salts of esters.
The phosphoric acid derivatives of the present invention prove to be especially suited. In this case RIn4 is OX~4 and RIm is OXIIf3~ wherein R~i, X~~, X~, A~1 and A~ contain the same meaning as in formula (III).
Particularly preferred phosphoric acid derivatives are chloroacetyl phosphoric acid (fosfono-chlorin), phosphonoformic acid (foscarnet), phosphonoacetic acid, N,N-dimethyl-(1-hydroxy-2-oxo-2-methoxy-ethyl)-phosphonamide and 2-hydroxy-2-hydroxymethyl-3-oxo-butylpho~i'~onic acid (phosphonothrixine) and ammonium-ethylcarb~ oyl phosphonate (fo-samine ammonium).
IV. Combined preparations of lipid metabolism inhibitor and organophosphorus com-pounds which contain at least one ether group or one keto group These compounds according to the invention correspond to the general formula (I~:
RL~ : 0 \ II
N-BIV-P-RL,~ ( IV) I

in which Rim and Rrv2 being the same or different are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted aryl, substituted and unsubstituted cycloal-kyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen, OXim and OXIV2, wherein XIm and Xwz are the same or different and are selected from the group which con-sists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hy-droxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, sub-stituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubsti-tuted cycloalkyl, substituted and un.substituted aralkyl, substituted and unsubstituted hetero-cyclic radicals, BIV is selected from the group which consists of ether group (IVA) Y
- Azvi - 0 - Arvz - i -Z
wherein AIVI and AIV2 of which A,v2 also may be abse~ are the same or different and are se-lected from the group which consists of alkylene radical, alkenylene radical and hydroxyal-kylene radical, keto group (IVB) N
- A~v3 - C - A=~.ra - ( I~ ) wherein AIVS and AIVa, of which one or also both may be absent, are the same or different, are selected from the group which consists of alkylene radical, Alkenylene radical and hy-droxyalkylene radical, and 5 and 6 membered cyclic, in particular heterocyclic compounds, which contain addition-ally to carbon at least one heteroatom as a ring member, wherein the heteroatom is selected from the group which consists of oxygen and nitrogen, Riv3 and Rlva being the same or different are selected from the group which consists of hydro-gen, substituted and unsubstituted alkyl having up to 26 carbon atoms, substituted and unsub-stituted hydroxyalkyl having up to 26 carbon atoms, substituted and unsubstituted aryl, sub-stituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsub-stituted alkenyl having up to 26 carbon atoms, substituted and unsubstituted alkynyl having up to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OXIVS or OXiva, wherein XIV3 or Xiv4 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl having up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl having up to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl having up to 26 carbon atoms, substituted and unsubstituted alkynyl having up to 26 carbon atoms, substi-tuted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, a silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium com-pounds which derive from ethylene diamine or amino acids, and their pharmaceutically accepmble salts, esters and amides and salts of esters.
In particular compounds are preferred which correspond to the formula (IVC) \ I II
N-AIVI-0-C-P-OXIVS ( IVC ) / I I

wherein Rivz is selected from the group which consists of acetyl and formyl, Aivi is selected from the group which consists of methylene, ethylene, ethenylene, hy-droxyethylene, 2-hydroxypropylene, and XIV3 and XIV4 are the same or different and are selected from the group which consists of so-dium, potassium, methyl, ethyl.
Preferably the chain -Aim-O-C(Z'Y)- consists of one oxygen atom and two or three carbon atoms (substituents are not taken into consideration), particularly preferred two carbon atoms.
Out of the ether compounds the compounds are particularly preferred which are selected from the group which consists of ((N-farmyl-N-hydroxyamino)-methoxy)-methylphosphonic acid disodium salt, ((N-acetyl-N-hydroxyamino)-methoxy)-methylphosphonic acid disodium salt, (2-(N-formyl-N-hydroxyamino)-ethenoxy)-methylphosphonic acid disodium salt, (2-(N-acetyl-N-hydroxyamino)-ethenoxy)-methyl-phosphoric acid disodium salt, (3-(N-formyl-N-hydroxvamino)-2-hydroxypropoxv)-methylphosphonic acid disodium salt, (3-(N-acetyl-N-hydroxvamino)-2-hydroxypropoxy)-methylphosphonic acid disodium salt.
Further those compounds are preferred, which correspond to the formula (IVD) \ II II
N-AIV3-C-AI'Ja-P-OXIVS ( Ice) / I
RIV2 ~XIV4 wherein Rivz is selected from the group which consists of acetyl and formyl, A~ is selected from the group which consists of rnethylene, ethylene, ethenylene, hydroxymethylene, hy-droxyethylene and 2-hydroxypropylene, AIVa is absent or is methylene, and X~
and Xiva are the same or different and are selected from the group which consists of a metal of the first, second or third main group of the periodic system, in particular sodium, potassium, and methyl, ethyl.
Preferably the chain -AIV1-CO-AIVZ- consists of two to four carbon atoms (substituents are not taken into consideration), particularly preferred of three carbon atoms.

Out of these compounds 2-(N-formyl-N-hydroxyamino~l-oxoethylphosphonic acid disodium salt, 2-(N-acetyl-N-hydroxyamino)-1-oxoethylphosphonic acid disodium salt, 3-(N-formyl-N-hydroxy amino)-I-oxopropylphosphonic acid disodium salt, 3-(N-acetyl-N-hydroxy amino)-1-oxopropylphosphonic acid disodium salt, 3-(N-formyl-N-hydroxyaminorl-oxo-2-propenyl-phosphoric acid disodium salt, 3-(N-acetyl-N-hydroxyamino)-1-oxo-2-propenylphosphonic acid disodium salt, 4-(N-formyl-N-hydroxyamino)-1-oxo-3-hydroxybutylphosphonic acid disodium salt, 4-(N-acetyl-N-hydroxyaminorl-oxo-3-hydroxybutyl-phosphoric acid disodium salt, 3-(N-formyl-N-hydrpxyamino~2-oxopropyl-phosphonic acid disodium salt, 3-(IJ-acetyl-N-hydroxyamino)-2-oxoproylphosphonic acid disodium salt, 4-(N-formyl-N-hydroxyamino)-3-oxo-2-hydroxy-2-methylbutylphosphonic acid disodium salt, 4-(N-acetyl-N-hydroxyamino)-3-oxo-2-hydroxy-2-methylpropyl-phosphonic acid disodium salt, 4-(lt-formyl-N-hydroxyamino)-3-oxo-2-hydroxy-2-(hydroxymethyl)-butyl-phosphoric acid disodium salt, 4-(N-acetyl-N-hydroxyamino)-3-oxo-2-hydroxy-2-(hydroxymethyl)-propylphosphonic acid disodium salt are particularly preferred.
In the cyclic compour_'° the amino group and the phosphorus atom may be bounC ~~ any C-atoms of the ring. However, compounds are preferred, in which they are bound to two C-atoms, which are separated only by one additional atom. In the heterocyclic compounds both carbon atoms preferably are separated by one heteroatom.
The following compounds are particularly preferred:
Rlvl 0 \ N II
N P-OXIv:3 ( IVE ) / I

RIvI O
\ Q II
N -~ ~-P-OXIV:3 ( IVF) R~2 Rlvl 0 \ I I
N - P-OXIV3 ( IVG) / I

\ Q II
N - P-OXIVS ( Ice) / I

Additionally, substances are suitable in which the phosphoric acid or phosphinic acid or phosphinoyl group is replaced by a sulfonic group or sulfonyl group:

I I
- S-Riv-~ (VIIE) I I
O
V. Combined preparations of lipid metabolism inhibitor and organophosphorus com-pounds which contain at least one hydroay group The phosphoric acid derivatives according to the invention correspond to the general formula (V):

I - II
Bv-Av=-C-Av2-r OXv3 ( V ) I I
OH OXv,~
wherein Avl and Aw, out of which one or also both may be absent, are the same or dii~erent and are selected from the group which consists of an alkylene radical, contain an alkenylene radical and a hydroxyalkylene radical, and preferably the carbon chain -Avl-CHOH-Av2-consists of 2 to 5 carbon atoms, particularly preferred of 3-4 carbon atoms, Bv is selected from the group which consists of a radical of formula (VA) II .
Rvi-C- ( V~) wherein Rvl is selected from the group which consists of hydrogen, OH, substituted and un-substituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals and halogen, of a radical of the formula (VB) V2 ~ V3 HO-C-C- (VB) Rv4 OH

wherein Rvz, Rv3, and Rv4 are the same or differed and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hy-droxyalkyl, substituted and unsubh-tituted alkenyl, substituted and unsubstituted alkynyl, sub-stituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubsti-tuted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted hetero-cyclic radical, halogen, and of a radical of the formula (VC) 0 Rvs \C-C- (VC) Rv6 Rv~
wherein Rvs, Rv6 and Rv~ are the name or different and are selected from the group which consists of hydrogen, OH, substiW ted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted aryl, substituted and unsub-stituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted het-erocyclic radical, halogen, wherein Xv3 or Xva are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and un-substituted alkenyl, substituted and unsubstituted allcynyl, substituted and unsubstituted cy-cloalkyl, substituted and unsubstituted heterocyclic radical, a silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids, and their pharmaceutically acceptable salts, esters and amides and salts of esters.
Preferably Rvl in formula (VA) is a methyl group.
Preferably in formula (VB) Rvz and Rva are hydrogen and Rv3 is a methyl group.
Preferably in formula (VC) Rvs is a methyl group, Rv6 is selected from the group which con-sists of H, OH and methyl, and R~~ is a hydroxy group.
Particularly preferred are the compounds which correspond to the formula I II I II
H-C-C-C-Av2-F'-OXv3 ( VD ) I I I
H H OXv4 wherein Av2 is a straight hydroxyalkylene with 1 to 3 carbon atoms and Xv3 and Xva are the same or different and are selected from the group which consists of hy-drogen, a metal of the first, second or third main group of the periodic system, in particular sodium, potassium, and methyl, ethyl.
Out of these compounds 3,4-dihydroxy-5-oxo-hexylphosphonic acid disodium salt, 1,2,3,4-tetrahydroxy-5-oxo-hexylphospho~nic acid disodium salt, 2,3,4-trihydroxy-5-oxo-hexylphosphonic acid disodium salt, 1,2,3-trihydroxy-4-oxo-pentylphosphonic acid disodium salt and 2,3-dihydroxy-4-oxopentylphosphonic acid disodium salt are particularly preferred.
In particular additionally compounds are preferred which correspond to the formula I I I II
HO-C-C - C-A.,,2-P-OXv3 (VE) I I I I
H OH H OXva wherein Av2 is a straight hydroxyalkylene with 1 to 3 carbon atoms and Xv3 and Xv4 are the same or different and are selected from the group which consists of hy-drogen, a metal of the first, second or third main group of the periodic system, in particular sodium, potassium, methyl and ethyl.
Out of these compounds 3,4,5-trihydroxy-4-meti~yl-pentylphosphonic acid disodium salt, 2,3,4,5-tetrahydroxy-4-methyl-pentylphosphonic acid disodium salt, 1,3,4,5-tetra-hydroxy-4-methylpentylphosphonic acid disodium salt, 1,2,3,4,5-peatahydroxy-4-methyl-pentylphosphonic acid disodium salt are particularly preferred.
In particular also those compounds are preferred, which correspond to the formula \\ I I I I
C-C - C-Av2-P-OXv3 ( VF) / I I I
H OH H OXv9 wherein Av2 is a straight hydroxyalkylene or a straight alkylene and consists of 1 to 3 carbon atoms and Xv3 and Xva are the same or different and are selected from the goup which consists of hy-drogen, a metal of the first, second or third main goup of the periodic system, in particular sodium, potassium, and methyl, ethyl.
Out of these compounds 3,4-dihydroxy-4-methyl-5-oxo-pentylphosphonic acid disodium salt, 2,3,4-trihydroxy-4-methyl-5-oxo-pentylphosphonic acid disodium salt, 1,2,3-tri-hydroxy-4-methyl-5-oxo-pentylphosphonic acid disodium salt, 2-monohydroxy-3-methyl~4-oxo-butylphosphonic acid disodium salt, 1,2-dihydroxy-3-methyl-4-oxo-butylphosphonic acid disodium salt are particularly preferred.
VI. Combined preparation of lipid metabolism inhibitor and organophosphorus or or-ganosulfur compounds containing an amine or imine group The organophosphorus compounds according to the invention correspond to the general for-mula (VI):

I I
Bvm P' RvI a ( V I ) I

wherein Rv~3 and Rw4 are the same or different and are selected from the goup which con-sists of hydrogen, substituted and unsubstituted alkyl having up to 26 carbon atoms, substi-tuted and unsubstituted hydroxyalkyl having up to 26 carbon atoms, substituted and unsub-stituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substi-tuted and unsubstituted alkenyl having up to 26 carbon atoms, substituted and unsubstituted alkynyl having up to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radiicals, halogen, OXv~ or OXv~4, wherein Xvi3 or Xw4 are the same ~or different and are selected from the goup which consists of hydrogen, substituted and unsubstituted alkyl having up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl having up to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl having up to 26 carbon atoms, substituted and u.nsubstituted alkynyl having up to 26 carbon atoms, substi-tuted and unsubstituted cycloalkyl" substituted and unsubstituted heterocyclic radical, a silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids, and Bv~ is selected from the group which consists of the group (VIA) RVIl N-AvI - ( V IA ) RvI z and the group (VTB) RvII-N=AvI- (VIB) wherein Av~ is selected from the group which consists of an alkyleneamine radical, an alken-yleneamine radical, a hydroxyalkyleneamine radical, an alkyleneimine radical, an alkenylene imine radical and a hydroxyalkyleneimine radical, wherein the nitrogen atom is a member of the chain which connects the phosphorus atom with the nitrogen atom of the group / N- or the group R~i-N= , and RvI z in which Rvn ~d Rvu in group (VTA) are the same or different and Rvu and R~ in group (VTA) and Rvl1 in group (VTB) are selected from the group which consists of hydrogen, sub-stituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen, OXvii and OXv~, wherein Xurl and Xv~ are the same or different and are selected from the group which con-sists of hydrogen, substituted and unsubstituted allryl, substituted and unsubstituted hy-droxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted allrynyl, sub-stituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubsti-tuted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted hetero-cyclic radical, and their pharmaceutically acceptable salts, esters and amides and salts of esters.
Preferably, A~ is an amino group, in which the nitrogen atom is not in the end position. Pref erably, Av~ connects the nitrogen and the phosphorus atom by three atoms (without substitu-ents).
In particular those compounds are preferred, which correspond to the formula (VI) RvI i \ il N-AvI-P-Rvls (VI ) I

wherein Rvil, Rmz, Rms and Xvia are defined the same as in formula (VI), and Avi is selected from the group which consists of C-N-C, C'=N-C, C-N=C, wherein the carbon atoms may be substi-tuted with a hydroxy or alkyl group having up to 7 carbon atoms.
Particularly preferably Rvil is a hydroxy group, Rv~ is selected from the group which consists of acetyl and formyl, Rv~ is selected from the group which consists of hydrogen, methyl, ethyl, hexadecyl, octadecyl and OXvi3, and Xvi3 and Xvi4 selected from the group which con-sists of hydrogen, sodium, potassium, methyl, ethyl, hexadecyl and octadecyl, and may be, as far both are present, the same or different.
Further compounds are preferred which correspond to the formula (VID) II
Rvli-N=AvI-P-Rv-~ ( VID ) I
OXvI
wherein Roil, Rw, Rvi3 and Xvi4 are defined the same as in formula (I), and A is selected from the group which consists of C-N-C, C=N-C, C-N=C, wherein the carbon atoms may be substi-tuted with a hydroxy or alkyl group having up to 7 carban atom.
Particularly preferably Rvii is selected from the group which consists of acetyl and formyl, and R~-i3 is selected from the group which consists of hydrogen, methyl, ethyl, hexadecyl, octadecyl and OX~-r3, and Xvi3 and Xvl4 are selected from the group which consists of hydro-gen, sodium, potassium, methyl, ethyl, hexadecyl and octadecyl, and may be the same or dif ferent as far both are present.
VII. Combined preparation of lipid metabolism inhibitor with organophosphorus com-pounds, which contain a nitrogen heterocycte The organophosphorus compounds used according to the invention correspond to the general formula (VII):

II
RVII1-AVII1-P-RVII? VII
I

in which AvtI is selected from the soup which consists of (C1_9)-alkylene radical, which may comprise one or more double bonds and may be substituted with hydroxy, halogen, amino, oxo groups with branched or straight C1_9-alkyl groups and CZ_9-alkenyl groups, wherein the C,_9-alkyl groups and CZ_9-alkenyl groups may be substituted with hydrogen, hydroxy, amino, halogen and oxo groups, -C-O-C,'- ,end -C-N-C-, wherein the carbon atoms of-C-O-C- and -C-N-C- may be substituted with an alkyl having up to 7 carbon atoms or hydroxy groups, or in which A~i corresponds to the; following formula (VIIA):
~VII1 BVI=3 BVII5 BVII'7 BVII9 -C'JII1-CVI=2-C1'II3-C'JII4-CVIIS- ~ VI IA~
~'J=I2 BVI_4 BVII6 BVIIf3 BVII10 wherein one or more of the carbon atoms selected from the group Cvn3, Cvn~, Cvas may also be absent together with their substituents, and at least one present substitute of B~II to Bmo is a C3_8-cycloalkyl-(Co_9)-alkyl group, wherein the C3.~-cycloalkyl group as well as the Co_9-alkyl group may contain one or more double bonds and one or two carbon atoms of the cyclo-alkyl group may be replaced by nitrogen, oxygen or sulfur atoms, and wherein the cycloalkyl group as well as the alkyl group m<iy by substituted with hydroxy, halogen, amino, oxo groups, with branched or straight C',i.9-alkyl groups and with CZ_9-alkenyl groups, wherein the Ci_9-alkyl groups and C2_9-alkenyl groups may be substituted with hydrogen, hydroxy, amino, halogen and oxo groups, and the remaining present substituents Bval to Bvnlo are selected from the group which consists of hydrogen, hydroxy, halogen, amino groups, Ci.2s-alkyl radi-cals, C1_zb-alkoxy radicals, C,_26-alkOXy-C1_26-alkyl radicals or both substituents of one C-atom together form an oxo group, wherein each C1_26-alkyl radical and each Ci-26-alkoxy radi-cal may be branched or straight and saturated or unsaturated with one or more double bonds and may be substituted with hydroxy, amino, halogen and oxo groups, in which Rvnl is selected from the ;group which consists of 5 and 6 membered heterocycles with one or two nitrogen, oxygen or sulfur atoms in the rink wherein the heterocycle may be saturated or unsaturated with one or more double or triple bonds and may be substituted with hydroxy, halogen, amino, oxo groups and by branched or straight C1_9-alkyl groups and by C2_ 9-alke-nyl groups, wherein the Ci_9~-alkyl groups and CZ_9-alkenyl groups may be saturated or unsaturated with one or more double or triple bonds and may be substituted with hydrogen, hydroxy, amino, halogen and oxo groups, in which Rvrr3 and Rva4 are the same or different and are selected from the group which con-sists of hydrogen, substituted and unsubstituted Cr-z6-alkyl, hydroxy-Ci-z6-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aryl, substituted and unsubstituted aral-kyl, substituted and unsubstituted C1_z6-alkenyi, substituted and unsubstituted C,-z6-alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OXv~ and OXvna, wherein Xuru and X~.n4 are the same or different and are selected from the group which con-sists of hydrogen, substituted and unsubstituted Ci_z6-alkyl, substituted and unsubstituted hy-droxy-C1_z6-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C,_zb-alkenyl, substituted and unsubstituted C1-z6-alkynyl, sub-stituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, a silyl, a ration of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene di~~~ne or amino acids, -and their pharmaceutically acceptable salts, esters and amides and salts of esters.
If two heteroatoms are present in the heterocycle Rear, of course they also may be present in mixed form, for example an oxygen atom and a nitrogen atom.
Preferably Rvnl is a heterocycle containing nitrogen atoms, wherein substituted or unsubsti-tuted pyridine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyrroie and substituted or unsubstituted pyTazole are particularly preferred and N /~N
/.
or are especially particularly preferred.
Preferably the organophosphorus compound corresponds to the formula (V>ZC) II
RvI I l-A'~ I I-P-RVI I3 ( V I I C ) I

wherein Rv~ preferably is hydrogen, methyl, ethyl or an amide radical and X~4 is selected from the group which consists of hydrogen, sodium, potassium, methyl, ethyl, and particularly preferably correspond to the formula (VI1D) RVII:L3 RVIZI2 II
RVII1-AVII-P-OXVII3 (VIID) .
I

Additionally, substances are suitable in which the phosphoric acid or phosphinic acid or phosphinoyl goup is replaced by sulfonic goup or sulfonyl goup:

II
- S-RVI=~ (VIIE) II

VIII. Combined preparation of lipid metabolism inhibitor and phosphonoformic acid derivatives The compounds are described in VVIlO 98/16537.
The organophosphorus compounds used according to the present invention correspond to the general formula (VIII):

I

w ( CI'~RVIII9 ) n ~RVI

wherein the wavy line represents a bond which has either a- or (3-configuration, nis0orl, wherein Rvnm is selected from the goup which consists of substituted and unsubstituted Ci-26-alkyl, hydroxy-Ci-a6-alkyl, substituted and unsubstituted aryl, substituted and unsubsti-tuted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C,-26-alkenyl, substituted and unsubstituted Ci_26--alkynyl, substituted and:unsubstituted cycloalkyl, substi-tuted and unsubstituted heterocyclic radicals, halogen and OXvm 1, wherein Xvm i is selected from the goup which consists of hydrogen, substituted and unsub-stituted C,_26-alkyl, substituted and unsubstituted hydroxy-C,-26-alkyl, substituted and unsub-stituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted Ci-26-alltenyl, substituted and unsubstituted C,.z6-alkynyl, substituted and unsubstituted cycloaikyl, substi-tuted and unsubstituted heterocyclic radical, a siiyl, a canon of organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammoruum compounds which derive from ethylene diamine or amino acids, Rmn is selected from the group which consists of C1_za-alkyl radicals, Cz_z4-alkenyl radicals, Cz_z4-alkapolyenyl radicals, which contain 2 to 6 double bonds, Cz_za-alkynyl radicals, C3~-cycloalkyl radicals, C3_g-cycloalkyl-Ci_za-alkyl radicals and C1_iz-alkoxy-Ci_lz-alkyl radicals, Rvmz, Rvuu and Rv~a4 each are selected independently from the group which consists of hy-drogen, halogen, amino, acetylamino, azido and XRvai6-groups, wherein X is O
or S and Rvia6 is selected from the group which consists of a hydrogen radical, branched or straight C1~-alkyl radicals and Cz.~-alkenyl radicals, wherein the C1.~-alkyl radicals as well as the C2~-alkenyl radicals optionally may be substituted with hydrogen, amino, halogen or oxo groups, or RvInz, Rv~ and Rv~a4 together with the respective g-~?inal hydrogen group represent an oxo group, Rv~S is selected from the group which consists of hydrogen, C1_z4-alkyl groups, C3~-cycloalkyl radicals, ar(C1_za-alkyl) groups, aryl groups, aryl groups, heterocyclic radicals, halogen, wherein all radicals may be branched or straight and optionally may be substituted with hydroxy, amino, halogen or o:xo groups and may contain 2-6 double and triple bonds or Rv~S is a phenyl radical of the forrnula VRIA or X~, (VIIIA) RVIIIB
RvII:
- CH (VIIIB) RvI:.I a wherein Rv~~ and RvniB are the same or different and are bound to any two positions of the phenyl ring and are selected independently from the group which consists of hydrogen, halo-gen, C,.~-alkyl radicals, Cl.~-alkoxy radicals, formyl, acayl, propionyl, butyryl radicals, for-myl, acetyl, propionyl, butyryloxy radicals, Cz_s-alkoxycarbonyl radicals, which all may be branched or straight, or R~ and Rv~B may form together a straight saturated alkylene chain having 3 to 4 carbon atoms bound to adjacent positions, for example the 2,3-position or 3,4-position of the phenyl ring, or R~ and Rg together form a methylenedioxy radical, a 1,1-ethylidenedioxy radical or a 1,2-et:hylenedioxy radical, which are bound to the 2,3- or 3,4-positions of the phenyl ring, or Rums is selected from the group which consists of Rv~COOCHRv~IO- and RvrI~OCOOCHRvmio-, wherein Rv~ is selected from the group which consists of C,.~-alkyl radicals, Cz.~-alkenyl radicals, Cz~-alkynyl radicals, C3_f;-cycloalkyl radicals, C3~-cycloalkyl-Cm-alkyl radicals and C1.~-alkoxy-C1.~-alkyl radicals, wherein all radicals may be branched or straight and option-ally may be substituted with hydraxy, amino, halogen or oxo groups, and Rio is a branched or straight C1~-alkyl radical, and wherein the configurations of the substituents Rv~z, Rv~, Rv~4 and RvmsOOCPO(OH)OCHz- in (VIII) are selected independ_-tly from D-gluco, L-gluco, D-galacto, L-galacto, D-manno, L-m~anno, D-talo, L-talo, D-alto, L-alto, D-altro, L-altro, D-gulo, L-gulo, D-ido or L-ido, if n is 1 or the configurations of the substituents Rz, R3 and RSOOCPO(OH)OCHz- in I are independent D-ribo, L-ribo, D-arabino, L-arabino, D-xylo, L-xylo, D-lyxo or L-lyxo, if n is 0.
According to the invention the configuration of the glycosidic bond of the compounds is pref erably a.
Preferred compounds of formula (VIII) are those, wherein R~1 is selected from the group which consists of C9_z4-alkyl radicals, C9.za-alkenyl radicals, C9.z4-alkapolyenyl radicals, which contain 2 to 6 double bonds., C9_za-alkynyl radicals, C3~-cycloalkyl-C6_z4-alkyl radicals and C1-lz-alkoxy-Ca-lz-alkyl radicals, which each may optionally be branched or straight and may be substituted with hydrogen, amino, halogen or oxo radicals.
In particular the use of any compound is preferred, in which R~1 is selected from the group which consists of a n-tetradecyl radical, n-octadecyl-1-yl radical, a trams-9-octadecenyl radi-cal and a cis-9-octadecen-1- radical. Preferably Rv~z, Rvt~, Rvta4 each are hydroxy groups.
Preferably Rv~S is a hydrogen, a formyl group or a acetyl group. Furthermore n is preferably 1 and the configuration of the substituents Rva~z, Rvma, Rv>B4, and R~SOOCPO(OH)OCHz-is D-gluco.
Preferably Rv~ll represents OXviirn with Xvmn = hydrogen.

IX. Combined preparation of lipid metabolism in6ibntor and heterncyctic phospbono-formic acid derivatives The organophosphorus compounds according to the invention are described in and correspond to the formula (IX) ~Rixii (IX) RTx~ Rzxz wherein Rrxu is selected from the group which consists of substituted and unsubstituted Ci-zs-a"-~l, hydroxy-C1_zb-alkyl, substituted and unsubstituted aryl, °»bstituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C~_z6-alkenyl, sub-stituted and unsubstituted Ci_z6-alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen and OX~11, wherein XIxu is selected from the soup which consists of hydrogen, substituted and unsub-stituted C1_z6-alkyl, substituted and unsubstituted hydroxy-Ci_z6-alkyl, substituted and unsub-stituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1_z6-alkenyl, substituted and unsubstituted C,_zb-alkynyl, substituted and unsubstituted cycloalkyl, substi-tuted and unsubstituted heterocyclic radical, a silyl, a ration of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammo-nium, substituted ammonium and ammonium compounds which derive from ethylene dia-mine or amino acids, wherein R~1 and R~ each are selected independently from the group which consists of C1_za-alkyl radicals, C3_g-cycloalkyl radicals, C3_g-cycloalkyl-Ci_za-alkyl radicals, C1-za-alkoxy radi-cals, Cl.za- alkylthio radicals, C1-za-alkoxy-Ci_za-alkyl radicals and Ci_z4-alkylthio-Ci_z,~-alkyl radicals, aryl radicals, aryl radicals, aralkyl radicals, heterocyclic radicals, halogen and hy-drogen, and each Ci_za-alkyl radical and Ci_za-alkoxy radical may be branched or straight and may be saturated or unsaturated with 2 to 6 double bonds and optionally may be substituted with hydroxy, amino, mercapto, halogen, oxo groups or Ci-za-alkoxy radicals, C1_za-alkylcarbonyl-oxy radicals, Ci_z4-alkoxycarbonyloxy radicals, C1_z4-alkylthio radicals, Ci_za-alkylcarbonyl-thio radicals, Ci_za-alkylamino radicals, di-(C1_z4-alkyl)amino radicals, C1_za-alkylcabonyl-amino radicals, Ci_z4-alkyl-(Ci-za-alkylcarbonyl)amino radicals, Ci.za-alkoxycarbonylamino radicalsorCl.zo-alkyl-(Ci_z4-alkoxycarbonyl)amino radicals, wherein each aralkyl radical, heterocyclic radical, C,_z4-alkyl radical and C1_z4-alkoxy radical may be branched or straight and may be saturated or unsaturated with 2 to 6 double bonds or triple bonds, or wherein R~1-CH-CH-RIxz form part of a C~-carbon ring, which optionally may be substi-tuted with hydroxy, mercapto, amino, halogen, oxo groups or with C1_za-alkyl radicals, C,_za-alkoxy radicals, C1_za-alkylthio radicals, C~_z4-alkylamino radicals, di-(C1_z4-alkyl)amino-radicals, C1_za-alkylcabonyl radicals, C1_za-alkylcarbonyloxy radicals, C1_z4-alkoxycarbonyl radicals, C1_z4-alkylcarbonylthio radicals or C1_z4-alkylcarbonylamino radicals, C1_z4-alkyl-(Ci_ z4-alkylcarbonyl)-amino radicals, all C1_za-alkyl radical may be branched or straight and satu-rated or unsaturated with 1 to 6 double bonds, or wherein Rixio is a branched or straight C1~-alkyl radical, and wherein R~1-CH-CH-Rn,z form a opart of the furanose or pyranose ring of a sugar, for exam-ple D-ribose, D-arabinose, D-xylose, D-lyxose, D-glucose, D-galactose, D-mannose, D-talose, D-allose, D-altrose, D-gulose, D-idose or the corresponding L-isomers, wherein the hydroxy groups each may be optionally substituted with hydrogen, amino, azido, oxo, mer-capto radicals or C~_z4-alkoxy radicals, C~-za-alkylthio radicals, Ci-za-alkylamino radicals, di-(C,_z4-alkytlamino radicals, C1_2.~-alkylcabonyloxy radicals, Ci-za-alky~~arbonylthio radicals, C1_z4-alkylcarbonylamino radicals, Cl-za-alkyl-(C~_z4-alkylcarbonyl)amino radicals, wherein each C1_z4-alkyl radical may be branched or straight and saturated or unsaturated with 1 to 6 double bonds, and their pharmaceutically acceptable salts, esters and amides and salts of es-ters as well as their optical isomers.
In particular RIx, and RIxz each may be selected independently from the group which consists of carboxyl radicals, carboxamido radicals, aryl radicals, aryloxycarbonyl radicals, aryl-Ci_za-alkyl radicals, Ci-za-alkoxycarbonyloxy radicals, C1_za-alkylaminocarbonyl radicals, di-(Ci_z4-alkyl)-aminocarbonyl radicals, aryl-C1_z4-alkoxycarbonyl radicals, aryl-Ci_za-alkylamino- car-bonyl radicals, C1_z4-alkylcabonyloxy-(C1~)-alkylmethoxycarbonyl radicals, Ci.za-alkoxy-carbonyloxymethoxycarbonyl radicals, Ci-za-alkoxycarbanyl-oxy-(C1~-alkyl)-methoxycarbonyl, wherein each C, _z4-alkyl radical may be branched or straight and saturated or unsaturated with 2 to 6 double bonds, and each C1~-alkyl radical and Ci_za-alkoxy radical may be branched or straight and saturated or unsaturated, and each aryl radical corresponds to the formula IXA
( IXA) RIx3 wherein R~ and R~4 are the same or different and each are selected from the group which consists of hydrogen, halogen, C,.~~-alkyl radicals, C~.~-alkoxy radicals, formyl, acetyl, propi-onyl, butyryl radicals, formyl, acetyl, propionyl, butyryloacy radicals, Ci_a-alkoxy carbonyl radicals, which all may be branched or straight, or R~ and Rya together form a straight satu-rated alkylene chain with 3 to 4 carbon atoms, which is bound to adjacent positions of the phenyl ring, or R~ and R~4 together form a methylene dioxy radical, a 1,1-ethylidenedioxy radical or a 1,2-ethylenedioxy radical which is bound to adjacent positions of the phenyl ring.
The use of compounds is preferred, in which R~1 and Roz each are independently selected from the group which consists of hydrogen, hydroxy groups, formyl, acetyl and methyl, wherein the methyl radical optionally may be substituted with a hydroxy group or mercapto group or with Ci_z4-alkoxy radicals,, C~-za-alkylcarbonyloxy radicals, Ci-za-alkyithio radicals or C1_za-alkylcarbonylthio radicals, wherein the C1_za-alkyl groups and the Ci_za-alkoxy groups may be branched or straight and saturated or unsaturated with 1 to 6 double bonds.
Rixl is particularly preferred a methyl radical, which optionally may be substituted with a hydroxy group or -~°rcapto group or by C~_z4-alkoxy radicals, C1_Za-alkylcarbc-~~Toxy radicals, Ci.za-alkylthio radicals or C1-z4-alk;ylcarbonylthio radicals, wherein the CI_za-alkyl graups and the C1_z4-alkoxy groups may be branched or straight and saturated or unsaturated with 1 to 6 double bonds, and R~z a hydrogen radical.
Especially good results are achieved by compounds, wherein Rixl and R~z each is independ-ently selected from the group which consists of hydrogen and a n-octadecylmethyl radical, wherein RIxI is preferably a n-octa~decylmethyl radical and Rz is a hydrogen radical. gpecial advantages are achieved, if the compound is of configuration (R).
Preferably Rixu represents OX~,1 with Xixil = hydrogen.
X. Combined preparation of lipid metabolism inhibitor and hydrory aminooaocarbyl derivatives The hydroxy aminooxocarbyl derivative used according to the present invention correspond to the general formula (X):

\ 11 N-C-Rx= r C X ) Rxi wherein Rxl is selected from the group which consists of hydrogen, substituted and unsubsti-tuted C1_9-alkyl, substituted and unsubstituted hydroxy-C1_9-alkyl, substituted and unsubsti-tuted C1_9-alkenyl, substituted and unsubstituted C~_9-alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen and OXXi, wherein Xxi is selected from the group which consists of hydrogen, substituted and unsubsti-tuted Ci_9-alkyl, substituted and unsubstituted hydroxy-C,_9-alkyl, substituted and unsubsti-tuted C~_9-alkenyl, substituted and unsubstituted C,_9-alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, wherein R~ is selected from the group which consists Of Ci-z6-alkyl radicals, C1_zs-alkoxy radicals, Ci_z6-alkoxy-Ci_z6-alkyl- radicals, C3_s-cycloalkyl-(Co_z6)-alkyl radicals, wherein one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms, each C3_z6-alkyl radical and each C3_z6-alkoxy radical being branched or straight and each C3_g-cycloalkyl radical, each C.z_26-alkyl radical and each C2_26-alkOXy radical may be saturated or unsaturated with one or more double bonds and each C3-s-cycloalkyl radical, each C~_zb-alkyl radical and each C~_z6-alkoxy radical may be substituted with hydroxy, amino, halogen and oxo groups ~~ with the. carbyl group CORD, wherein R~ is selexted from the group which consists of substituted and unsubstitute;d C1_z6-alkyl, hydroxy-C1_~-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1_26-alkenyl, sub-stituted and unsubstituted C1_z6-alk~~rnyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen and OXx~, wherein X~ is selected from the group which consists of hydrogen, substituted and unsubsti-tuted Cl.z6-alkyl, substituted and urisubstituted hydroxy-C1_26-allcyl, substituted and unsubsti-tuted aryl, substituted and unsubstii:uted aralkyl, substituted and unsubstituted Cl_z6-alkenyl, substituted and unsubstituted C~_z6-~ynyl, substituted and unsubstituted cycloalkyl, substi-tuted and unsubstituted heterocyclic radical, a silyl, a ration of organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids,.
Preferably R~ represents the carboxylic acid group POOH, wherein Rxi is a branched or straight C,.~-alkyl croup, particularly preferred an isopropyl group, as well as their pharma-ceutically acceptable salts, esters arid amides.
The salts of the carboxylic acid group are preferred, in which H is replaced by a metal of the first, second or third main group of the periodic system, ammonium or substituted ammo-nium, or ammonium compounds, which derive from ethylene diarnine or amino acids. Le. the salt compounds of hydroxy aminooxocarbylcarbonic acid derivatives and organic or inorganic bases (for example sodium salt, potassium salt, calcium salt, aluminium salt, ammonium salt, magnesium salt, triethyl amine salt, ethanol amine salt, dicyclohexyl amine salt, ethylene diamine salt, N,N-dibenzylethylene diamine salt etc.) as well as salts of amino acids (for ex-ample arginine salt, asparagine acid salt, glutamine acid salt etc.) and the like are formed.
Preferably additionally esters of the carboxylic acid group may be formed.
Suitable examples of such esters are suitable mono and diesters, and preferred examples of such esters include alkylester (for example hexadecanylester, octadecanylester etc.).
XI. Combined preparation of lipid metabolism inhibitor and organophosphorus com-pounds, which either contain two oayphosphorus groups or one oayphosphorus group and one oaysulfur group The organophosphorus compounds used according to the present invention correspond to the general formula (X17:

II n Rxzi-~:.:WAxWP-Rx3 I I
~v:~2 Rxla wherein ZM is a phosphorus atom or a sulfur atom, wherein A~ is a straight Cz_9-alkylene chain having substituents which are the same or differ-ent and are selected from the group which consists of hydrogen, hydroxy, halogen, amino and oxo groups, Ci_z6-~y1 radicals, C1_26-alkoxy radicals, Ci_z6-a~oxy-Ci_26-alkyl radicalsorC~-cycloalkyl-(Co_9)-alkyl radicals, wherein each C1_~-alkyl radical and each Ci-26-~oxy radical may be branched or straight and saturated or unsaturated with one or more double bonds and may be substituted with hydroxy, amino, halogen and oxo groups and the C3.s-cycloalkyl group as well as the Co-9-alkyl group of the C3~-cycloalkyl-(C~9)-alkyl group may contain one or more double bonds and one or two carbon atoms of the cycloalkyl group may be re-placed by nitrogen, oxygen or sulfur atoms, and wherein the cycloalkyl group as well as the alkyl group may be substituted with hydroxy, halogen, amino, oxo groups with branched or straight C1_9-alkyl groups and Cz_9-alkenyl groups, wherein the C1_9-alkyl groups and CZ_9-alkenyl groups may be substituted with hydrogen, hydroxy, amino, halogen and oxo groups, wherein R~1 and R~ are the same or different and are selected from the group which con-sists of hydrogen, substituted and unsubstituted Ci_9-alkyl, substituted and unsubstituted hy-droxy-C1_9-alkyl, substituted and unsubstituted Ci_9-alkenyl; substituted and unsubstituted Ci_9-alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubsti-tuted heterocyclic radical, halogen, OX~1 and OX~, wherein XMl and XMZ are the same or different and are selected from the group which consists of hydrogen, substituted and unsub-stituted C1_9-alkyl, substituted and unsubstituted hydroxy-Ci-9-alkyl, substituted and unsub-stituted C1_9-alkenyl, substituted and unsubstituted C1-9-alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted ~acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, wherein RM3 and R~4 are the same or different and are selected from the group which con-sists of substituted and unsubstituted Ci_26-alkyl, hydroxy-Ci_z6-alkyl, substituted and unsub-stituted aryl, substituted and unsub;stituted acyl, substituted and unsubstituted aralkyl, substi-tuted and unsubstituted C,_26-alken,yl, substituted and unsubstituted C1_26-alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OX~ and OX~4, wherein Xx~ and X~4 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted Ci_2s-alkyl, substituted and unsubstituted hydroxy-Ci_z6-alkyl, substituted and unsubstituted aryl, substituted and unsub-stituted aralkyl, substituted and unsubstituted C1_zs-alkenyl, substituted and unsubstituted C1_ 26-alkynyl, substituted and unsubstituted cycloallryl, substituted and unsubstituted heterocyclic radical, silyl, cation of an organic amd inorganic base, in particular a metal of the first, second or third main group of the period~~ system, ammonium, substituted ammonium and ammo-nium compounds which derive from ethylene diamine or amino acids, and their pharmaceutically acceptable salts, esters and amides and salts of esters.
Preferably A~ is a C3_5-alkyl chain.
Particularly preferred are compounds, in which R~ represents a methyl group and Z~, R~1, Rxis, Rya ar'e defined the same as above, wherein R~1 is preferably substituted with a hy-droxy group at the C-axom adjacent to the heteroatom, and compounds, in which R~ represents a hydroxy group wherein Z~, RMI, Rte, R~4 is defined the same as above, wherein RHIl is preferably an acyl group, particularly preferably is a formyl, acetyl, propionyl or butyryl group.
Also compounds having the following structures are preferred:

II II n Rxzi-Zxz-C-C-C-C-P-Rxzs (XIA) I I
OH l~xi 4 II I a , Rxll-Zx~-C-C-C-C-F'-Rxr3 ' (XIB) , I I
Rx~~ RXI9 RXII-IZXI-C-C-C-C-IP-RXI3 (XIC) .

I
Rxlz OH

I

II
II (XID) , RxII-ZxI-C-C-C-C-:P-RxI3 I i Rx.~ 2 ~ZxI a II J~I II II
RxWZx:-~-C-C-C-'---P-RxI3 (XIE) .
I

I
OH OH

II I I II
RxII-ZX=-C-C-C-C-~~-P-RXIS (XIF) , I

I
RX=~ RxI a (I ( II II
Rxli-Zt.=-C-C-C-C-C-P-RxI3 (XIG) and I ' Rx.=~ OH

II

II II I (XIH) .
RxII-Z:;=-C-C-C-C-C-P-RXIS
l OH Rxla XII. combined preparation of lipid metabolism inhibitor with 3~isoaazolidinones and hydrozy amine acids These compounds are described in US patent document 4 405 357.
The compounds according to the invention contained in the pharmaceutical compositions cor-respond to the general formula (I):
O R:s__a AXII- ,C - N-O-RxIIS (XI I ) wherein A~ is selected from the group which consists of hydrogen, substituted and unsub-stituted Ci_zg-alkyl radicals, substituted and unsubstituted alkoxy-(Co-ze)-alkyl radicals, sub-stituted and unsubstituted cycloalkyl-(Co_zg)-alkyl radicals, substituted and unsubstituted cy-cloalkoxy-(Co_z8)-alkyl radicals, substituted and unsubstituted amino-(C0.zs)-alkyl radicals and substituted, unsubstituted thio-(Co..zB)-alkyl radicals and substituted or unsubstituted acyl-(Co_ z8)-alkyl radicals and halogen, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or straight and each alkyl radical, each alkoxy radical each aryl radi-cal and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms, R~ is selected from the group which consists of hydrogen, substituted and unsubstituted alkyl groups, substituted and unsubstituted allcoxy-(Co_z6)-alkyl radicals, substituted and un-substituted C3_~a-cycloalkyl-(Co_z6)-alkyl radicals, substituted and unsubstituted Cycloalkoxy-(Co_z6)-alkyl radicals, substituted and unsubstituted amino-(Co_z6)-alkyl radicals, substituted and unsubstituted silyl-(C0.z6)-alkyl radicals and substituted and unsubstituted thio-(C,~z6)-alkyl groups, wherein each alkyl radical and each alkoxy radical may be branched or straight and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cy-cloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms, or a carbon chain made of two C-atoms in A~ forms a ring together with Rte, such that an isoxazolidone ring is formed, and R~I4 is selected from the group which consists of hydrogen, substituted and unsubstituted alkyl radicals, substituted and unsubstituted acyl radicals and substituted and unsubstituted cycloalkyl-(Co-z6)-a~y1 radicals, wherein each alkyl radical and each acyl radical may be branched or straight and each alkyl radical, each acyl radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms.
Preferably A~ corresponds to the formula (XIIA) RXII6- C - C - ( I I ) I I
RxII~ RXII2 wherein R~1 and R~~z are the same or different and are selected from the group which con-sists of hydrogen, hydroxy, halogen, substituted and unsubstituted amino radicals, substituted and unsubstituted alkyl radicals, substituted and unsubstituted alkoxy radicals and substituted and unsubstituted cycloalkyl-(C0.zs,)-alkyl radicals, wherein each alkyl radical and each alkoxy radical are branched or straight and each alkyl radical, each alkoxy radical and each cycloal-kyl group are saturated or unsaturai:ed with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl radicals may be replaced by-'nitrogen, oxygen or sulfur atoms, RCS, R~6 and R~ are the same or different and are selected from the group which consists of hydrogen, hydroxy, halogen, substituted and unsubstituted alkyl groups, substituted and unsubstituted cycloalkyl-(Co-z6)-a~:yl radicals, substituted and unsubstituted cycloalkoxy-(Co_ z6~-a~yl radicals, substituted and u:nsubstituted alkoxy-(Co_z6)-alkyl radicals, substituted and unsubstituted amino groups and substituted, unsubstituted thio-(C0.z6)-alkyl radicals and sub-stituted or unsubstituted aryl radicals, wherein each alkyl radical, each alkoxy radical and each acyl radical is branched or straight and each alkyl radical, each alkoxy radical and each cycloalkyl group is saturated or unsaturated with one or more double or tzzple bonds and one or two carbon atoms of the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms, wherein R~5 may alternatively form a ring with RHII~, and R~ and R~I~ may comprise a, carbon-oxygen-simple bond such that a ring structure is present.
The invention also includes the pharmaceutically acceptable salts, esters and salts of esters.
Preferably R~1 and RMU are the same or different and selected from the group which consists of substituted and unsubstituted alkyl group, preferably C1-Ca-alkyl groups.
Preferably R~ is selected from the group which consists of hydrogen, substituted and unsub-stituted alkyl group, preferably C,-Ca-alkyl groups, substituted and unsubstituted aromatic C~-C14-cycloalkyl radicals, a pyranyl ~~oup and a t-butyldimethylsilyl group and -C- RxIIa wherein RMIS is selected from the group which consists of substituted and unsubstituted, pref erably with halogen substituted allc:yl groups, substituted and unsubstituted cyloalkyl(Co_zs)-alkyl radicals, substituted and unsubstituted amino groups, substituted and unsubstituted alk-oxy groups, substituted and unsubstituted phenoxy groups, substituted and unsubstituted al-kylthio groups, substituted and unsubstituted, preferably unsubstituted or with halogen, methyl, methoxy, vitro, amino or (:F3-groups substituted aromatic cycloalkylthio groups.
R~4 is preferably selected from the group which consists of hydrogen, substituted and unsub-stituted alkyl radicals, substituted and unsubstituted phenyl radicals and ZxII
-CHZ
YXI I ~ n wherein Z~ is selected from the group which consists of hydrogen, halogen, Cite-alkyl radi-cals and phenyl radicals and Y~ is selected from the group which consists of hydrogen, halo-methoxy-2,2-dimethylpropanamide;, 3,3-dichloro-N-(2-chlorophenyl)methyl-N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N-(2-fluorophenyl)methyl-N-hydroxy-2,2-dimethylpropan-amide, 3-bromo-N-(2-chlorophenylmethyl-N-hydroxy-2,2-dimethylpropanamide, N-benzoyloxy-3-chloro-N-(2-chlorophenyl)me:thyl-2,2-dimethylpropanamide, N-acetoxy-3-chloro-N-(2-chlorophenyl)methyl- 2,2-dimethylpropanamide, N-(chloroacetoxy}-3-chloro-N-(2-chlorophenyl)methyl-2,2-dimethylpropanamide, 2-{2-chlorophenyl)methyl-4,4-dimethyl-3-isoxazolidinone, 4,4-dimethyl-2-phenyl-3-isoxazolidinone, 2-(2-bromophenyl)methyl-4,4-dimethyl-3-isoxazolidinone, 4,4-diamethyl-2-(2-methyl-phenyl)methyl-3-isoxazolidinone, 2,4-trimethyl-3-isoxazolidinone, 4,4-dimethyl-2-phenylmethyl-3-isoxazolidinone, 2-(2,4-dichlorophenyl)methyl-4,4-dimethyl-3-isoxazolidinone, ~-chloro-2-(2-chlorophenyl)me;thyl-4,4-dimethyl-3-isoxazolidinone, 2-(2-chlorophenyl)methyl-5-methoxy-4,4-dimethyl-3-isoxazolidinone, 2-(2-fluorophenyl)methyl-4,4-dimethyl-3-isoxazolidinone, N-[(2-chlorophenyl)methyl]-N,3-dihydroxy-2,2-dimethylpropanamide, 3-chloro-N-[(2-chlorophenyl)methyl]-2,2-dimethy:l-N-(methylamino-carbonyloxy)propanamide, 3-chloro-N-[(2-chlorophenyl)methyl]-N-[(2-tetrahydropyranyl)oxyl-2,2-dimethyl-propanamide, 3-chloro-N-[(2-chlorophenyhmethyl]-2,2-dimethyl-N-[dimethyl(1,1-dimethyl-ethyl)silyloxy pro-panamide, 3-acetoxy-N-((2-chlorophenoxy)-methyl]-N-hydroxy-2,2-dimethylpropan amide, 2,((2-chloro-4-fluorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, 2-[(2-chloro-5-fluorophenyl)methyl]-4,4-dimethyl.-3-isoxazolidinone, 2-[(2,4,5-trichlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, 2-[(2-chloro-6-fluorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, 2-[(2-chlorophenyl)methyl]-5-ethoxy-4,4-dimethyl-3-isoxazolidinone, 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-5-phenylamino-3-isoxazolidinone, 2-[(2-chlorophenyl)methyl]-5-hydroxv-4,4-dimethyl-3-isoxazolidinone, 3-chloro-N-[(2-chlorophenyl)methyl]-2,2-dimethyl-N-[(phenylamino)carbonyloxy]-propanamide, 3-chloro-N-[(2-chlorophenyl)methyl]-2,2-dimethyl-N-([(2-chlorophenyl)methyl]-2,2-dimethyl-N-phenoxycarbonyl-oxy)propanamide, 3-chloro-N-[(2-chlorophenyl)methyl]-N-ethoxy-carbonyloxy-2,2-dimethylpropanamide, N-benzoyloxy-3,3-dichloro-N-[(2-chlorophenyl)methyl]-2,2-dimethylpropanamide, N-(2-bromophenyl)methyl-3,3-dichloro-N-hydroxy-2,2-dimethyl)propanamide, 3-chloro-N-[(2-chlorophenyl)methyl]-N-(4-nitrobenzoyloxy)-2,2-dimethylpropanamide, 3-chloro-N-[2-chlorophenylmethyl)]-2,2-dimethyl-N-[(2-methylphenyl)carbonyloxy]propanamide, 3-chloro-N-dichloroacetoxy-N-[(2-chlorophenyl)methyl]-2,2-dimethylpropanamide, 3-chloro-N-[2-chlorophenyl)methyl)-2,2-dimethyl-N-[(4-methylphenyl)sulfanyloxy]propanamide, 3-chloro-N-[2-chloro-phenyl)methyl]-2,2-dimethyl-N-[( l,1-dimethylethyl)carbonyl-oxy]propanamide, 3-chloro-N-[2-chlorophenyl)-methyl]-2,2-dimethyl-N-(ethylthiocarbonyloxy)propanamide, 3-chloro-N-[(2,2,2-trichloroethoxy)carbonyloasy)-N-[(2-chlorophenyl)methyl]-2,3-dimethylpropanamide, 3-chloro-N-[(2-chlorophenyl)aminocarbonyl-oxy-N-[(2-chlorophenyl)methyl]-2,2-dimethylpropanamide, 3-chloro-N-[(4-chlorophenyl)aminocarbonyloxy-N-[(2-chlorophenyl)methyl]-2,2-dimethyl-propanamide, 3-chlaro-N-[2-chlorophenyl)methyl]-2,2-dimethyl-N-(phenylmethoxy)-propanamide, 3-chloro-N-[(2,4-dichlorophenyoxy)acetoxy)-N-[(2-chlorophenyl)methyl]-2,2-dimethyl-propanamide, 3-chloro-N-[2-chlorophenyl)methyl]-2,2-dimethyl-N-[(3-trifluoromethyl)benzoyloxypropananude, 3-chloro-N-[2-chloro-phenyl)methyl]-2,2-dimethyl-N-[(4-methylphenyl)aminocarbonyl-oxy}-propanamide, :3-chloro-N-[2-chlorophenyl)methyl]-N-[(3,4-chlorophenyl)aminocarbonyloxy]-2,2-dimethylpropanamide, 3-chloro-N-(3-chloro-2,2-dimethyl-1-oxo-propoxy~N-[(2-chlorophenyl)-methyl]-2,2-dimethyllpropanamide, 3-bromo-N-[(2-bromophenyl)-methyl]-N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N-[(2-chlorophenyl)-methyl]-N-[(2-fluorophenyl)aminocarbonyloxy]-2,2-dimethylpropanamide, 3-chloro-N-[(2-chlorophenyl)methyl]-N-[(4-methoxyphenyl)aminocarbonyloxy]-2,2-dimethylpropanamide, 3-chloro-N-[(2-chlorophenyl)methyl]-N-[(3-trifluormethylphenyl)-aminocarbonyloxy]-2,2-dimethylpropanamide, 3-bromo-N-[(2-chlorophenyl)methyl]-N-(methylaminocarbonyloxy)-2,2-dimethyl-propanamide, 3-bromo-N-(2-chloroacetoxy~N-[(2-chlorophenyl)-methyl]-2,2-dimethylpropanamide, 3-chloro-N-[2,5-dichloro-(formylamino)-benzoyl]oxy-N-[(2-chloro-phenyl)methyl]-2,2-dimethylpropar~amide, 3-bromo-N-[(2-bromophenyl)methyl]-N-chloroacetoxy-2,2-dimethylpropanamide, 3-bromo-N-[(2-bromophenyl)-methyl]-N-(methyl-carbonyloxy)-2,2-dimethylpropanamide, 3-bromo-N-[(2-bromophenyl)methyl]-N-[(2-chlorophenyl)aminocarbonyloxy]-2,2-dimethylpropanamide, 2-[(2-chlorophenyl)methyl]-N-hydroxy-2,2-dimethyl-3-methylthio-propanamide, 3-phenylcarbonyloxy)-N-[(2-chlorophenyl)-methyl]-N-hydroxy-2,2-dimethylpropanamide, 2-[(4-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, 2-[(3,4-dichlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, 2-[(chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone-5-ylacetate, 2-[(chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone-5-ylbenzoate, 2-[(chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone-S-yldichloroacetate, 2-[(chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone-5-ylphenylcarbamate, 2-[(chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone-5-ylmethyl-carbamate, 2-[(2-chloro-4-cyanophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, 2-[(2-chloro-5-methoxyphenyl) methyl]-4,4-dimethyl-3-isoxazolidinone, 2-[(2-chloro-4-methoxyphenyl)-methyl]-4,4-dimethyl-3-isoxazolidinone, 2-[(2,4-difluorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, 2-[(4-bromo-2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, 2-[(2-bromo-fluorphenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, 2-[(6-chloro-1,3-benzdioxol-~-yl)methyl]-4,4-dimethyl-3-isoxazolidinone, 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-5-phenoxy-3-isoxazolidinone, 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-5-(1-methylethoxy)-3-isoxazolidinone, 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-5-(phenylmethoxy)-3-isoxazolidinone, 2-[(2-bromophenyl)methyl]-5-chloro-4,4-dimethyl-3-isoxazolidinone, 2-[(2,5-dichlorophenyl)methyl]-4,4-dimethyl--3-isoxazolidinone, 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-5-propoxy-3-isoxazolidinone, 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-S-(2-propenyloxy)-3-isoxazolidinone, 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-5-(2-propinyl-oxy)-3-isoxazolidinone, 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-S-(2-methoxyethoxy)-3-isoxazolidinone, 2-[(4-fluoro-2-iodophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, :2-[(2-chlorophenyl)methyl]-5-cyclopentoxy-4,4-dimethyl-3-isoxazolidinone, 2- [(2-chlorophenyl)-methyl]-4,4-dimethyl-5-(4-nitophenoxyr3-isoxamlidinone, 2-[(2-chlorophenyl)methyl]-5-cyclopropyl-methoxy-4,4-dimethyl-3-isoxazolidinone, 2-[(2-bromophenyl-(methyl)]-4,4-dimethyl-5-(2-propinoxy)-3-isoxaz,olidinone, 2-[(Z-chlorophenyl)methyl]-5-(3-butinoxy)-4,4-dimethyl-3-isoxazolidinone, 2-((2-ch~lorophenyl)methyl]-S-(2-butinoxy)-4,4-dimethyl-3-isoxazolidinone, 2-[(2-chlorophenyl)methyl]-5-(3-butenoxy)-4,4-dimethyl-3-isoxazolidinone, 2-[(2-chlorophenyl)-methyl]-5-pentoxy-4,4-dimethyl-3-isoxazolidinone, 2-[(2-chloro-phenyl)methyl]-S-hexoxy-4,4-dimc;thyl-3-isoxazolidinone, 2-[(2-chlorophenyl)methyl]-5-(1-methylpropoxy)-4,4-dimethyl-3-isoxazolidinone, 2-[(2-chlorophenyl)methyl]-5-(3-methyl-3-butenoxy)-4,4-dimethyl-3-isoxazolidinone, 2-[(2-chlorophenyl)-methyl]-5-butoxy-4,4-dimethyl-3-isoxazolidinone, 2-[(2-chloro-phenyl)methyl]-4,4-dimethyl-3-isoxazolidinone.
XII>Q. Combined preparation of lipid metabolism indibitor with thiadiazole derivatives The thiadiazole derivatives used according to the present invention correspond to the general formula (XIII): ' RXIiI3 (XIII) ~XIII1 s ~0) n S !fix==s XIII6 wherein n is an integer from 0 to 4, and wherein R~1, R~~z, R~~, R~I4, R~uS and R~6 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl radicals, sub-stituted and unsubstituted alkoxy radicals, substituted and unsubstituted acyl radicals, substi-tuted or unsubstituted cycloalkyl-(Co-z6)-alkyl radicals, substituted and unsubstituted cycloal-kyl-(Co-zb)-alkoxy radicals and halogen, wherein each alkyl radical, each allcoxy radical and each acyl radical may be branched or straight and each alkyl radical, each acyl radical, each alkoxy radical and each cyclo-(Co:z6)-alkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms.
Preferably R~i represents COOC'.zHs.

_38_ Furthermore compounds are preferred, in which R~ to R~6 are selected from the group which consists of hydrogen and halogen, in particular chlorine,.
Preferably n furthermore represents 1 or 2.
XIV. Combined preparation of lipid metabolism inhibitor and a nitrogen-orygen-heterocycle The compounds according to the invention contained in the pharmaceutical compositions cor-respond to the general formula (XI's):

Y~ Iv N-Bxm-Z:~IV (XIV) /, Rxlv, Rxlva wherein Y,~v is a C,_3-alkenylene group, which is substituted with the substituents R,avl and R,~z and optionally with the substituents R,~v3 to R,~6, wherein R,~~, to R,~,s are the same or different and are selected from the group which consists of hydrogen, hydroxy, halogen, sutrstituted and unsubstituted alkyl groups, substituted and unsubstituted cycloalkyl-(Co-zs)-alk:yl radicals, substituted and unsubstituted cycloalkoxy-(Co.
z6)-alkyl radicals, substituted and unsubstituted alkoxy-(C'.o-z6)-alkyl radicals, substituted and unsubstituted amino groups and substituted, unsubstituted thin-(Co-z6)-alkyl radicals, substi-tuted and unsubstituted sulfonyl-(C'o.z6)-alkyl radicals, substituted and unsubstituted sulfinyl-(CO-26)'~yl radicals and substituted or unsubstituted aryl radicals, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or straight and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with ane or more double or triple bonds and one or two carbon atoms the cycloalkyl radicals may be re-placed by nitrogen, oxygen or sulfiu atoms and R,~,13 and R,Q,~14 are defined the same as R,~1 to R,Q,~ or together form an oxo group, wherein Z~v represents the organophosphorus group I I

Rxlvi o wherein RMV9 ~a Rxrvio are the same or different and are selected from the group which con-sists of hydrogen, substituted and unsubstituted (C,_~~alkyl groups, substituted and unsub-stituted hydroxy-(C~.2s)-alkyl radicals, substituted and unsubstltuted cycloalkyl-(Cp.26)-alkyl radicals, substituted and unsubstituted acyl, halogen, OX~v9 or OX~vio, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or straight and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms, wherein XHIV9 or XMVm are the same or dif ferent and are selected from the group which consists of hydrogen, substituted and unsubsti-tuted (C1_26)-alkyl groups, substituted and unsubstituted hydroxy-(C~-z6)-~y1 radicals, sub-stituted and unsubstituted cycloalkyl-(Co_26)-alkyl radicals, substituted and unsubstituted acyl, a silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or straight and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and on.e or two carbon atoms of the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms, or wherein ZMV represents the amino group -N-R:.:=m i Rxr:
wherein R,~~l and R~m2 are the same or difFerent and are selected from the group which con-sists of hydrogen, substituted and unsubstituted alkyl groups, substituted and unsubstituted cycloalkyl-(Co_26)-alkyl radicals, substituted and unsubstituted cycloalkoxy-(C0.26)-alkyl radi-cals, substituted and unsubstituted alkoxy-(Co_26)-alkyl radicals and substituted or unsubsti-tuted acyl radicals, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or straight and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two car-bon atoms of the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms, wherein BMV is selected from the soup which consists of substituted and unsubstituted C1_26-alkenylene groups, wherein a C-atom may be replaced by an oxygen atom and a C-atom may be replaced by a sulfur atom or two C-atoms may be replaced by an S-hetrocycle and wherein each alkenylene radical may be branched or straight and saturated or unsaturated with one or more double or triple bonds and m.ay be substituted with one or more hydroxy groups, halo-gen groups or oxo groups.
Preferably RMVis ~d Rxrvi4 together form an oxo group in a-position regarding the nitrogen atom.

Preferably Y,av represents a methylene group, which is particularly preferably substituted with two methyl groups.
Furthermore compounds are advantageous, in which B,Q" represents the ether group (XIVA) - Aim - O - A~v2 - (XIVA) wherein A~v~ is absent or a (C~-9)-~~lkylene radical, and AMV2 is absent or selected from the group which consists of (C1_9)-alkylene radicals, a sulfur atom and a (C3-a)-heterocycle, which comprises at least one sulfur atom. Particularly preferably AMVI and AMV2 each represent a methylene group.
Also compounds are advantageous, in which BMV represents the keto group (XIVB) II
- Axl~, _ -' r - A:;zva (XIVB) wherein Axivs and A~va, out of which one or both may be absent, are the same or different and are selected from the group which consists of (C1_9)-alkylene radicals, wherein all (C,_9)-alkylene radicals may be branched or straight, may contain one or more double bonds or may be substituted with a hydroxy group or a halogen group.
Particularly preferred A~v3 is absent and A~va represents a methylene or an ethylene group.
Preferably BMV is further a 2-hydroxypropylene group.
RHIV9 and RMmo preferably represent OX~v9 and OX~vro, wherein XMV9 and XMmo are the same or different and are selected from the group which consists of a metal of the first, second or third main group of the periodic system, in particular sodium and potassium, and methyl, ethyl.
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 thioacid or inudic acid corresponding to the individually present acids, or from an organic sulfonic acid, wherein in each case these acids comprise aliphatic, aromatic and/or heterocyclic groups in the molecule as well as carbamoyl or car-bamimidoyl.
Suitable examples of these acyl groups were given below:.

Acyl radicals originating from aliphatic acid are designated as aliphatic acyl groups and in-elude:
Alkanoyl (e.g. formyl, acetyl, propi.onyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl etc.);
alkenoyl (e.g. acryloyl, methacrylo:yl, crotonoyl etc.);
alkylthioalkanoyl (for example methylthioacetyl, ethylthioacetyl etc.) alkane sulfonyl (for example mesyl, ethane sulfonyl, propane sulfonyl etc.);
alkoxycarbonyl (for example methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopro-poxycarbonyl, butoxycarbonyl, isobutoxycarbonyl etc.);
alkylcarbamoyl (for example niethylcarbamoyl etc.);
(N-alkyl)-thiocarbamoyl ( for example (N-methyl~thiocarbamoyl etc.);
alkylcarbamimidoyl (for example rnethylcarbamimidoyl etc.);
oxalo;
alkoxalyl (for example methoxalyl, ethoxalyl, propoxalyl etc.).
In the above examples of aliphatic acyl groups the aliphatic hydrocarbon part, in particular the alkyl group and the alkane radical may optionally contain one or more suitable substituents, such as amino, halogen (for example fluorine, chlorine, bromine etc.), hydroxy, hydroxy-imino, carboxy, alkoxy (for example methoxy, ethoxy, propoxy etc.), alkoxycarbonyl, acyla-mino (for example benzyloxycarbonylamino etc.), acyloxy (for example acetoxy, benzoyloxy etc.) and the like. Preferred aliphatic acyl radicals with such substituents are for example al-kanoyls substituted with amino, carboxy, amino and carboxy, halogen, acylamino or the like.
Acyl radicals originating from an acid with substituted or unsubstituted aryl groups, wherein the aryl group may comprise phenyl, toluyl, xylyl, naphthyl and the like are designated as aromatic acyl radicals. Suitable examples are given below:
Aroyl (for example benzoyl,~toluoyl, xyloyl, naphthoyl, phthaloyl etc.);
Aralkanoyl (for example phenylacetyl etc.);
Aralkenoyl (for example cinnamoyl etc.);
Aryloxyalkanoyl (for example phe,noxyacetyl etc.);
Arylthioalkanoyl (for example phe;nylthioacetyl etc.);
Arylaminoalkanoyl (for example lJ-phenylglycyl, etc.);
Arene sulfonyl (for example benzene sulfonyl, tosyl bzw. toluene sulfonyl, naphthalene sul-fonyl etc. );
Aryloxycarbonyl (for example phenoxycarbonyl, naphthyl-oxycarbonyl etc.);
Aralkoxycarbonyl (for example bc;nzyloxycarbonyl etc.);
Arylcarbamoyl (for example phenylcarbamoyl, naphthylcarbamoyl etc.);
Arylglyoxyloyl (for example phenylglyoxyloyl etc.).

In the present examples of aromatic acyl radicals the aromatic hydrocarbon part (in particular the aryl radical) and/or the aliphatic hydrocarbon part (in particular the alkane radical) may optionally contain one or more suitable substituents, such as those which were already men-tioned as suitable substituents of the; alkyl group and the alkane radical. In particular and as an example for preferred aromatic acyl radicals with particular substituents, aroyl substituted with halogen and hydroxy or by halogen and acyloxy and acyloxy and aralkanoyl substituted with hydroxy, hydroxyimino, dihalogenalkanoyloxyimino are mentioned as well as arylthiocarbamoyl (for example phe;nylthiocarbamoyl etc.);
arylcarbamimidoyl (for example phenylcarbamimidoyl etc.).
A heterocyclic acyl radical is understood to be an acyl radical which originates from an acid with heterocyclic group. These include:
heterocyclic carbonyl in which the heterocyclic radical is an aromatic or aliphatic 5 to 6 membered heterocvcle and has at least one heteroatom from the group nitrogen, oxygen and sulfur (for example thiophenyl, furoyl, pyrrolcarbonyl, nicotynoyl etc.);
heterocyclic alkanoyl, in which the heterocyclic radical is 5 to 6 membered and has at least one heteroatom from the group nitrogen, oxygen and sulfur (for example thiophenyl-acetyl, furylacetyl, imidazolylpropionyl, te;trazolylacetyl, 2-(2-amino-4-thiazolyl)-2-methoxyiminoacetyl etc.) and the liike.
In the above examples of heterocyclic acyl radicals the heterocycles and/or the aliphatic hy-drocarbon part may optionally contain one or more suitable substituents, such as the same as those which were mentioned as suitable for alkyl and alkane groups.
"Alkyl" is a straight- or branched-chain alkyl radical having up to 9 carbon atoms, unless de fined otherwise, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert.-butyl, pentyl, hexyl and the like.
"Alkenyl" includes straight- or branched-chain alkenyl groups with up to 9 carbon atoms, unless defined otherwise, for example vinyl, propenyl (for example 1-propenyl, Z-propenyl), 1-methylpropenyl, 2-methylpropenyl, butenyl, 2-ethylpropenyl, pentenyl, hexenyl.
"Alkynyl" includes straight- or branched-chain alkynyl radicals having up to 9 carbon atoms, unless defined otherwise.
Cycloalkyl preferably represents an optionally substituted C3 to C~
cycloalkyl. alkyl, alkoxy (for example methoxy, ethoxy etc.), halogen (for example fluorine, chlorine, bromine etc.), vitro and the like are inter alia suitable as possible substituents.
Aryl is an aromatic hydrocarbon radical such as phenyl, naphthyl etc., which may optionally contain one or more suitable substituents such as alkoxy (for example methoxy, ethoxy etc.), halogen (for example fluorine, chlorine, bromine etc.), vitro and the like.
"Aralkyl" includes mono-, di-, triphenylalkyls such as benzyl, phenethyl, benzhydryl, trityl and the like, wherein the aromatic part may optionally contain one or more suitable substitu-ents such as alkoxy (for example methoxy, ethoxy etc.), halogen (for example fluorine, chlo-rine, bromine etc.), vitro and the like.
"Alkylene" includes straight- or branched-chain alkylene groups, which contain up to 9 car-bon atoms and may be represented by the formula -(CaH2a)-in which n is an integer from 1 to ~~, such as methylene, ethylene, iximethylene, methylethyl-ene, tetramethylene, 1-methyltrimethylene, 2-ethylethylene, pentamethylene, 2-methvltetramethylene, isopropylethylene, hexamethylene, and the like.
Preferred alkylene radicals contain up to 4 carbon atoms and radicals with 3 carbon atoms, such as for example trimethylene are particularly preferred.
"Alkenylene" includes straight- or branched-chain alkenylene groups with up to 9 carbon at-oms which may be reproduced by the formula:
-(CnH2a-2)-in which n is an integer from 2 to ~~, for example vinylene, propenylene (for example 1-propenylene, 2-propenylene), 1-methylpropenylene, 2-methylpropenylene, butenylene, 2-ethylpropenylene, pentenylene, he:xenylene and the like. The alkenylene radical may particu-larly preferably contain up to 5 carbon atoms and in particular 3 carbon atoms, for example 1-propenylene.
"Hydroxyalkylene" may include straight- or branched-chain alkylene radicals which contain up to 9 carbon atoms, wherein one or more selected carbon atoms are substituted with a hy-droxy group. These radicals may be represented by the formula:
'(~2n-z)W~-in which n is an integer from 1 to 9 and z is an integer, to which z < n applies. Suitable exam-ples of such hydroxyalkylene groups include hydroxymethylene, hydroxyethylene (for exam-ple 1-hydroxyethylene and 2-hydroxyethylene), hydroxytri~ethylene (for example hydroxytrimethylene, 2-hydroxytrimethylene and 3-hydroxytrimethylene), hydroxytet-ramethylene (for example 2-hydroxytetramethylene), 2-hydroxy-2-methyltrimethylene, hy-droxypentamethylene (for example 2-hydroxypentamethylene), hydroxyhexamethylene (for example 2-hydroxyhexamethylene) and the like. A lower hydroxyalkylene with up to 4 car--bon atoms is particularly preferred and in particular one with 3 carbon atoms for example 2-hydroxytrimethylen.
"Alkyleneamine" includes straight:- or branched-chain alkylene amine groups, which contain up to 9 carbon atoms and may be represented by the formula:
-~CnH2n)-N-~C~2m)-in which n and m may be the same: or different and be an integer from 0 to 9, to which 1 < n +
m < 9 applies, such as methyleneamine, ethyleneamine, dimethylene amine, trimethylene amine, methylene ethyleneamine, tetramethylene amine, 1-methyltrime;thylene amine, 2-ethylethylene amine, ethylenemethylene amine, pentamethylene amine, 2-methyltetramethylene amine, isopropylethylene amine, hexamethylene amine, and the like.
Preferred alkylene amine radicals .contain 2 carbon atoms, which are end positioned. Dimeth-ylene amine is particularly preferred. The hydrogen atoms may be replaced by substituents, for example halogen radicals.
"Alkyler°~mine" includes straight- or branched-chain alkyleneimine soups, which contain up to 9 carbon atoms and may be represented by the formula -(C.,Hzn-r )=N-Oa~zm)-or the formula -(CnH2n)-N=(C~nH2n,-1)-in which n and m may be the same or different and are an integer from 0 to 9, to which 1 < n - m < 9 applies, such as methyleneimine, ethyleneimine, dimethyleneimine, trimethyle-neimine, methylenethyleneimine, tetramethyleneimine, 1-methyltrimethyleneimine, '~-ethylethyleneimine, ethylenemethyleneimine, pentamethyleneimine, 2-methyltetramethyleneimine, isopropylethyleneimine, hexamethyleneimine, and the like. Pre-ferred alkylene imine radicals contain 2 carbon atoms, which are end positionexl. Dimethyle-neimine is particularly preferred. 7Che hydrogen atoms may also be replaced by substituents, for example by halogen radicals.
"Alkenyleneamine" includes straight- or branched-chain alkenylene amine groups having up to 9 carbon atoms, which may be represented by the formula -(~2n-2)-N-~~2m-2)-, -(Cof~2o)"N-OnH2n-2)-, -W2n-2)-N-(CoH2o)-in which n and m are the same or different and are an integer from 2 to 9, to which m + n < 9 applies, and o is a number between 0 and 7, to which o + n < 9 applies, for example vinyl-eneamine, methylenevinyleneamine, divinyleneamine, propenyleneamine (for example 1-propenyleneamine, 2-propenyleneamine), methylenpropenyleneamine, 1-methylpropenyleneamine, 2-methylpropenyleneamine, butenyleneamine, 2-ethylenepro-penyleneamine, pentenyleneamine:, hexenyleneamine, vinylmethyleneamine and the like. The hydrogen atoms may also be replaced by substiiuents, for example by halogen radicals.

"Alkenyleneimine" includes straight- or branched-chain alkenylene imine groups having up to 9 carbon atoms, which may be represented by the formula -(CnH2n-3)-N-(~2m-2)-, -(CoH2o-l)-N-(~2m-2)-; -(~2a-3~N-(CoH2o)-;
-(~2n-2)-N-(~2m-3)-; -(CoH2o)"N-(~2m3~, -(~2n-2)-N-(CoH2o-1)-in which n and m are the same or different and are an integer from 2 to 9, to which m + n < 9 applies, and o is a number from U to 7, to which o + n < 9 applies, for example vinyleneimine, methylenevinyleneimine, ethylenevinyleneimine, propenyleneimine (for example 1-propenylene imine, 2-propenylene imine), methylenepropenyleneimine, 1-methylpropenyleneimine, 2-methylpropenyleneimine, butenyleneimine, 2-ethylenepro-penyleneimine, pentenyleneimine, hexenyleneimine, vinylemethyleneimine and the like. The hydrogen atoms may also be replaced by substituents, for example by halogen radicals.
"Hydroxyalkyleneamine" may be straight- or branched-chain alkylene radicals which contain up to 9 carbon atoms, wherein at lE;ast one selected carbon atom is substituted with a hydroxy group; these radicals being represented by the formula -(CnH2n-z)(~~' -N-(CmH2m-Y)(OH)Y
in which n and m are the same or different and are an integer from 0 to 9, to which 1 < n + m < 9 applies, and z and y are the same or different and are an integer, to which 0 < z < n and 0 < y < m ~d y + z > 1 applies. Suitable examples of such hydroxyalkyleneamine groups in-clude hydroxymethyleneamine, hydroxyethyleneamine (for example 1-hydroxyethylenamine and 2-hydroxyethyleneamine), hydroxytrimethyleneamine (for example 1-hydroxytrime-thylene, 2-hydroxvtrimethylenamine and 3-hydroxytrimethyleneamine), hydroxytetra-methylene amine (for example 2-hydroxytetramethyleneamine), 2-hydroxy-2-methyltri-methyleneamine, hydroxypentamethyleneamine (for example 2-hydroxypentamethylene-amine), hydroxyhexamethyleneam.ine (for example 2-hydroxyhexamethyleneamine), methyl-enehydroxymethyleneamine, methylenehydroxyethyleneamine and the like. A lower hy-droxyalkylene amine with 2 carbon atoms and one nitrogen atom is particularly preferred wherein both carbon atoms are end positioned. The hydrogen atoms may also be replaced by substituents, for example by halogen radicals.
"Hydroxyalkyleneimine" includes straight- or branched-chain alkylene radicals, which con-tain up to 9 carbon atoms, wherein. at least one selected carbon atom is substituted with a hy-droxy group. These radicals may be represented by the formula -(~2n-z-1)(~~ -~-(Cmfi2m-Y)(~~ ~ -(CnH2n-z-1)(~~-N~~2m-Y)( in which n and m are the same or different and are an integer from 0 to 9, to which 1 < n + m < 9 applies, and z and y are the same or different and an integer, to which 0 < z < n-l and 0 <
y < m-1 and y + z > 1 applies. Suitable examples of such hydroxyalkyleneimine groups in-clude hydroxymethyleneimine, hydroxyethyleneimine (for example 1-hydroxyethyleneimine and 2-hydroxyethyleneimine), hydroxytrimethyleneimine (for example 1-hydroxytri-methyleneimine, 2-hydroxytrimethyleneimine and 3-hydroxytrimethyleneimine), hydroxy-tetramethyleneimine (for example 2-hydroxy-tetramethyleneimine), 2-hydroxy-2-methyl-trimethylene imine, hydroxypentarnethyleneimine (for example 2-hydroxypentamethylene-imine), hydroxyhexamethyleneimine (for example 2-hydroxyhexamethyleneimine), methyle-nehydroxymethyleneimine, methylenehydroxyethyleneimine and the like. A lower hy-droxyalkyleneimine with 2 carbon atoms and a nitrogen atom, wherein the two carbon atoms are end positioned, is particularly preferred. The hydrogen atoms may also be replaced by substituents, for example by halogen radicals.
The 5 and 6 membered cyclic Compounds, which are represented by Brv may be aromatic or aliphatic and may be substituted for example by alkyl groups with up to 7 carbon atoms and hydroxy groups.
The 5 and 6 membered heterocyclic compounds, which may be represented by Real and Rwi2 as well as Rxl and Rte, and which contain beside carbon one or two nitrogen, oxygen or sulfur atoms as a ring member, ma.y be saturated or unsaturated.
"Alkoxy radical" is, unless defined otherwise, a straight- or branched-chain alkoxy radical having up to 26 carbon atoms, such as a methoxy, ethoxy radicals, etc.. It may be substituted for example by hydroxy, amino, halogen, oxo groups and alkoxy radicals, such as methoxy-, ethoxy radicals.
"Alkoxy-(Co_26)-alkyl radicals" are alkoxy radicals, which may also be bound to the basic structure upon an alkyl radical. The alkyl- and alkoxy groups are defined the same as above.
"Cycloalkyl-(Co_26)-alkyl radicals"' are cyclic compounds having 3 to 8 carbon atoms, unless defined otherwise, which are bound to the basic structure directly or upon an alkylene radical.
The alkylene radical may be branched, straight and saturated or unsaturated with double bonds. Possible substituents of the: cycloalkyl radicals are inter alia alkoxy radicals, alkyl radicals, hydroxy radicals, halogen radicals, amino radicals, oxo radicals.
Providing a respec-tive number of double bonds, the c;ycloalkyl radicals may also be aromatic, i.e. may be aryl-(Co_26)-alkyl radicals (for example phenyl, pyridyl, naphthyl etc.). In particular the aromatic cyclic compounds may further contain substituents, such as vitro groups and CF3 and phenyl radicals.
r "Cycloalkoxy-(Co_26)-alkyl radicals" are cyclic compounds with 3 to 8 carbon atoms, which are bound to the basic structure directly at an oxygen or upon an a.lkylene radical. The al-kylene radical may be branched, straight and may be saturated or unsaturated with double bonds. Possible substituents of the; cycloalkyl radicals are inter alia radicals (also alkylenedi-oxy radicals, such as methylenedio:xy), alkyl radicals, hydroxy radicals, halogen radicals, amino radicals, oxo radicals. Providing the respective number of double bonds the cycloalkyl radicals may also be multicycles and aromatic (for example phenoxy, pyridoxy, naphthoxy etc.). In particular the aromatic cyclic compounds further may contain substituents, such as vitro groups, CF3-groups and phenyl radicals.
For example the "amino radicals" rnay be substituted for example with the with the above defined alkyl radicals or cycloalkyl-(Co-zs)-alkyl radicals.
"Amino-(Co-z6)-alkyl radicals" are amino radicals, which also may be bound to the basic structure upon an alkyl radical. The; alkyl and amino groups are defined the same as above.
"Silyl radicals" may be substituted for example with the above defined alkyl radicals or cy-cloalkyl-(Co_z6)-alkyl radicals.
"Silyl"-(Co_z6)-alkyl radicals" are silyl radicals, which also may be bound to the basic struc-ture upon an alkyl radical. The alkyl and silyl groups are defined the same as above.
"Thio-(Co_z6)-alkyl radicals" may be substituted for example with the above defined alkyl radicals or cycloalkyl-(Co_z6)-alkyl radicals. The (Co_z6)-alkyl groups are straight- or branched-chain alkylene radicals such as methylene, ethylene, propylene, isopropylene, butylene, iso-butylene, tert.-butylene, pentylene, hexylene and the like. They may contain double or triple bonds and be substituted for example with hydroxy, amino, halogen (for example fluorine, bromine, chlorine), oxo radicals and alkoxy radicals, such as methoxy, ethoxy radicals.
Preferably, the radicals Xu to Xw3 and XI4 t0 Xva4 as well as Rv~S, R~r 1, X~
and XM~, Xal and Xriz may be selected such, that esters form on the phosphono group or the sulfonyl group.
Suitable examples of esters of the compounds used according to the present invention are suitable mono and diesters, and preferred examples of such esters includes alkylester (for ex-ample methylester, ethylester, propylester, isopropylester, butylester, isobutylester, hexylester etc.);
aralkyl ester (benryl ester, phenethyl ester, benzohydryl ester, trityl ester etc.);
aryl ester (for example phenyl ester, toluyl ester, naphthyl ester etc.);
aroylalkyl ester (for ex-ample phenacyl ester etc.); and silylester (for example of trialkylhalogensilyl, dialkyldihalo-gensilyl, alkyltrihalogensilyl, dialkylarylhalogensilyl, trialkoxyhalogensilyl, dialkylaralkyl-halogensilyl, dialkoxydihalogensil:yl, trialkoxyhalogensilyl etc.) and the like.
With the above esters the alkane and/or arene part may optionally contain at least one suitable substituent such as halogen, alkoxy, hydroxy, vitro or the like.

X~ to Xvu3 and Xta to Xvua as well as X~ and X~~, Xm and XIU are preferably a metal from the first, second or third main group of the periodic system, ammonium, substituted ammo-nium, or ammonium compounds, which derive from ethylene diamine or amino acids. In other words the salt compounds of the ammonium phosphoric acid derivatives with organic or inorganic bases (for example sodium salt, potassium salt, calcium salt, aluminium salt, ammonium salt, magnesium salt, triethylamine salt, ethanolamine salt, dicyclohexylamine salt, ethylenediamine salt, N,N-dibenzylethylenedi amine salt etc.) as well as salts with amino acids (for example arginine salt, aspartic acid salt, glutamic acid salt etc.) and the like.
The compounds according to the invention in accordance with the formulae (I) to (XI~ per-mit for example the emergence of spatial isomers for groups containing double bonds or chi-ral groups R or A or B or Y or Z or X. The use of the compounds according to the invention includes all spatial isomers both as pure substances and in form of their mixtures.
Pharmaceutically acceptable salts of the aminohydrophosphonic acid derivative include salts, which form the compounds according to the invention in their protonised form as an ammo-nium salt of inorganic or organic acids, such as hydrochloric acid, sulfur acid, citric acid, malefic acid, fumaric acid, tartaric acid, p-toluene sulfonic acid.
Salts which are formed by suitable selection of X3 (Xu to Xv3) and X4 (XI4 to Xv4) as well as XII1 and Xaz are especially suited, such as sodium salt, potassium salt, calcium salt, ammo-nium salt, ethanolamine salt, trieth.ylamine salt, dicyclohexylamine salt and salts of amino acid such as arginine salt, aspartic acid salt, glutamic acid salt.
The lipid metabolism inhibitors according to the invention contain one or more inhibitors of lipid metabolism. Inhibitors may b~e used which control the intake of fats as well as inhibitors, which control the synthesis of fats. The inhibitors include anion exchangers, preferably cho-lestyr amine and colestipol, (3-sito:rterol, nicotinic acids and their derivatives, such as nicotinyl alcohol, clofibrate and their derivatives, such as clofibrin acid ethylester, as well as their ana-logues, such as bezafibrate, fenofibrate and gemfibrozil, and probucol.
The inhibitors, which control the synthesis of fats, include HMG-CoA
synthetase inhibitors, HMG-CoA reductase inhibitors, preferably lovastatin, mevastatin, simvastatin, fluvastatin, atorvastatin, pravastatin and cerivastatin, inhibitors the squalene synthetase, preferably pyro-phosphate, pyrophosphate derivatives, bisphosphonic acid derivatives, phosphinylmethyl-phosphonic acid derivatives, phosphinylformyl dezivatives, phosphonocarboxyl derivatives, phosphonosulfonic acid derivatives, phosphinylmethylphosphonic acid derivatives, inhibitors of the squalene monooxygenase and other inhibitors of the synthesis of cholesterol.

Inhibitors of the HMG-CoA-reductase and inhibitors of the squalene synthetase are especially preferred.
Out of the bisphosphonates clodronate, etidronate, pamidronate, ibandronate, alendronate, zoledronate, risedronate, tiludronat:e and cimadronate are especially preferred.
Upon simultaneous, separate or successive administration together with inhibitors of lipid metabolism synthesis the infectiously active compounds and their esters as well as their salts show a strong cytotoxic efficacy against unicellular and multicellular parasites, fungi, bacteria and cells infected by viruses. The compounds according to the invention are usable in the treatment of infectious diseases which are caused by parasites, fungi, bacteria or viruses in humans and animals. The compounds are also suitable for the use for preventing these dis-eases.
The lipid metabolism inhibitoz~ ~re: effective against unicellular parasites (protozoa), in par ticular against pathogens of malaria and the sleeping sickness as well as the Chagas' disease, the toxoplasmosis, amoebic dysentery, leishmaniasis, trichomoniasis, pneumocystosis, balan-tidiasis, cryptosporidiasis, sarcocystosis, acanthamebiasis, naegleriasis, coccidiosis, giardiasis and lambliosis.
Therefore, they are particularly suitable as malaria prophylactics and as prophylactics of sleeping sickness as well as the Chagas' disease, toxoplasmosis, amoebic dysentery, leishma-niasis, trichomoniasis, pneumocystosis, balantidiasis, cryptosporidiasis, sarcocystosis, acan-thamebiasis, naegleriasis, coccidiosis, giardiasis and lambliosis.
The lipid metabolism inhibitors according to the invention may in particular be used against the following bacteria:
Bacteria of the family Propionibacteriaceae, in particular the genus Propionibacterium, in particular the species Propionibacterium acnes; bacteria of the family Actinomycetaceae, in particular the genus Actinomyces; bacteria of the genus Corynebacterium, in particular the species Corynebacterium diphteriae and Corynebacterium pseudotuberculosis;
bacteria of the family Mycobacteriaceae, the genus Mycobacterium, in particular the species Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium bovis;and Mycobacterium avium; bacte-ria of the family Chlamydiaceae, in particular the species Chlamydia trachomatis and Chla-mydia psittaci; bacteria of the genus Listeria, in particular the species Listeria monocytoge-nes; bacteria of the species Erysipelthrix rhusiopathiae; bacteria of the genus Clostridium;
bacteria of the genus Yersinia, the species Yersinia pestis, Yersinia pseudotuberculosis, Yer-sinia enterocolitica and Yersinia ruckeri; bacteria of the family Mycoplasmatacxae, the genus Mycoplasma and Ureaplasma, in particular the species Mycoplasma pneumoniae;
bacteria of the genus Brucella; bacteria of the genus Bordetella; bacteria of the family Neiseriaceae, in particular the genuses Neisseria and Moraxella, in particular the species Neisseria meningiti-des, Neisseria gonorrhoeae and Moraxella bovis; bacteria of the family Vibrionaceae, in par-ticular the genuses Vibr-io, Aeromonas, Plesiomonas and Photobacterium, in particular the species Vibrio cholerae, Vibrio anguillarum and Aeromonas salmonicidas;
bacteria of the genus Campylobacter, in particular' the species Campylobacter jejuni, Campylobacter coli and Campylobacter fetus; bacteria of the genus Helicobacter, in particular the species Helicobac-ter pylori; bacteria of the families Spirochaetaceae and the Leptospiraceae, in particular the genus Treponema, Borrelia and Leptospira, in particular :Borrelia burgdorferi;
bacteria of the genus Actinobacillus; bacteria of the family Legionellaceae, the genus Legionella; bacteria of the family Rickettsiaceae and family Ba.rtonellaceae; bacteria of the genus Nocardia and Rho-dococcus; bacteria of the genus Dermatophilus; bacteria of the family Pseudomonadaceae, in particular the genuses Pseudomona.s and Xanthomonas; bacteria of the family Enterobacteria-ceae, in particular the genuses Escr~richia, Klebsiella, Proteus, Providencia, Salmonella, Ser-ratia and Shigella; bacteria of the family Pasteurellaceae, in particular the genus Haemophilus;
bacteria of the family Micrococcaceae, in particular the genus Micrococcus and Staphylococ-cus; bacteria of the family Streptococcaceae, in particular the genus Streptococcus and Ente-rococcus and bacteria of the family Bacillaceae, in particular the genus bacillus and clostrid-ium.
Accordingly, the lipid metabolism inhibitors according to the invention are suitable for treat-ment of diphtheria, acne vulgaris, listeriosis, erysipelas in animals, gas gangrene in humans and in animals, diseases in humans and animals caused by clostridium septicum, tuberculosis in humans and animals, leprosy, and further mycobacteriosis in humans and animals, paratu-berculosis in animals, pestis, mesenterial lymphadenitis and pseudotuberkulosis in humans a.nd animals, cholera, legionnaires disease, borrelioses in humans and animals, leptospiroses in humans and animals, syphilis, campylobacter enteritides in humans and animals, moraxella keratoconjunctivitis and serositis in. animals, brucelloses in animals and in humans; anthrax in humans and animals, actinomycosi;s in humans and animals, streptotrichosis, psittako-sis/ornithosis in animals, and Q-fever and ehrlichiosis.
Further the use is advantageous in helicobacter eradication therapy of ulcers of the gastro-entenc tract.
Further combinations with an additional antibiotic may also be used for treatment of the above mentioned diseases. As lipid metabolism inhibitors with other antiinfective agents in particular isoniazide, rifampicin, ethambutol, pyrazinamide, streptomycin, protionamide and dapson are suitable for the treatment of tuberculosis.
The lipid metabolism inhibitors according to the invention may furthermore be used in par-ticular in infections with following viruses:
Parvoviridae: parvo viruses, dependo viruses, Denso viruses; Adenoviridae:
adeno viruses, mastadeno viruses, aviadeno viruses; Papovaviridae: papova viruses, in particular papilloma viruses (so called wart viruses), Polyoma viruses, in particular JC virus, BK
virus, and miopa-pova viruses; herpes viruses: all herpes viruses, in particular herpes simplex viruses, the varizella-zoster viruses, human cyt:omegalo virus, Epstein-Barr viruses, all human herpes vi-ruses, human herpes virus 6, human herpes virus 7, human herpes virus 8;
Poxviridae: pox viruses, orthopox, parapox, mollus,cum contagiosum virus, avipox viruses, capripox viruses, leporipox viruses; all primary hepatotropic viruses, Hepatitis viruses:
hepatitis A viruses, hepatitis B viruses, hepatitis C vinrses, hepatitis D viruses, hepatitis E
viruses, hepatitis F vi-ruses, hepatitis G viruses; Hepadna viruses: all hepatitis viruses, hepatitis B virus, hepatitis D
viruses; Picornaviridae: picorna viruses, all entero viruses, all polio viruses, all coxsackie vi-ruses, all echo viruses, all rhino viruses, hepatitis A virus, aphtho viruses;
Calciviridae: hepa-titis E viruses; Reoviridae: reo viruses, orbi viruses, rots viruses;
Togaviridae: toga viruses, alpha viruses, rubi viruses, pesti viruses, rubella virus; Flaviviridae: flavi viruses, ESME vi-rus, hepatitis-C-Virus; Orthomyxoviridae: all influenza viruses;
Paramyxoviridae: paramyxo viruses, morbilli virus, pneumo virus, measles virus, mumps virus;
Rhabdoviridae: rhabdo viruses, rabies virus, lyssa virus, vnscula stomatitis virus; Corona vir-idae:
corona viruses;
Bunyaviridae: bunya viruses, nairo virus, phlebo virus, uuku virus, hanta virus; Arenaviridae:
arena viruses, lymphocytic choriorneningitis-virus; Retroviridae: retro viruses, all H'I'L vi-ruses, human T-cell leukaemia vims, oncorna viruses, spuma viruses, lenti viruses, all HI-viruses; Filoviridae: Marburg and ~Ebola virus; Slow-virus-infections, prions;
Onco viruses, leukemia viruses.
The preparations used according to the invention are therefore suitable for fighting the fol-lowing viral infections:
Eradication of papilloma viruses to prevent tumors, in particular tumors in the sexual organs caused by papilloma viruses in humans, eradication of JC viruses and BK
viruses, eradication of herpes viruses, eradication of human herpes viruses 8 for the treatment of Kaposi' s sar-coma, eradication of cytomegalo viruses before transplants, eradication of Eppstein-Barr vi-ruses before transplants and to prevent tumors associated with Eppstein-Barr viruses, eradica-tion of hepatitis viruses for the treatment of chronic liver diseases and for the prevention of tumors of the liver and cirrhosis of the liver, eradication of ~coxsackie viruses patients with cardiomyopathy, eradication of co:~csackie viruses in diabetes mellitus patients, eradication of immune system debilitating viruses in humans and animals, treatment of secondary infections in AmS-patients, treatment of inflammations of viral origin of the respiratory tract (larynx papillomas, hyberplasias, rhinitis, pharyngitis, bronchitis, pneumonias), of the sensory organs (Keratoconjunctivitis), of the nervous system (poliomyelitis, meningoenzephalitis, encephali-tis, subacute sklerosing panencephalitis SSPE, progressive multifocal leukoencephalopathie, lymphocytic choriomeningitis), of the gastro-intestinal tract (stomatitis, gingivostomatitis, oesophagitis, gastritis, gastroenteritis, diarrhoea-causing diseases), the liver and the gall blad-der system (hepatitis, cholangitis, hepatocellular carcinoma), of the lymphatic tissue (mono-nucleosis, lymphadenitis), of the t~aematopoetic system, of the sexual organs (mumpsorchitis), of the skin (warts, dermatitis, herpes labialis, heat rush, herpes zoster, shingles), of the mu-cous membranes (papillomas, conjunctiva papillomas, hyperplasias, dysplasias), of the heart/blood vessel system (arteriitis, myocarditis, endocarditis, pericarditis), the kid-ney/urinary tract systems, of the sexual organs (anogenital lesions, warts, genital warts, acute condylomas, displasias, papillomas, cervix dyspiasias, candylomata acuminata, epidermodys-plasia verruci formis), of the organs of motion (myositis, myalgien), treatment of foot and mouth diseases in cloven-hoofed animals, of Colorado tick fever, of Dengue-syndrome, of haemorrhagic fever, of early sumrner meningoencephalitis (FSME) and of yellow fever.
The agents are suited for combination with other agents with antiviral characteristics.
The compounds used according to the invention which generally include pharmaceutically acceptable salts, esters, a salt of such an esters or else compounds which upon application provide the compounds use according to the invention metabolic products or decomposition products, also called "prodrugs" may all be prepared for administration like known anti-infectious agents in any suitable manner (mixed with non-toxic pharTnaceutically acceptable carriers).
The combined preparation used according to the invention may be administered together with non-toxic, inert pharmaceutically suitable carriers. These are understood to mean solid, semi-solid or liquid diluents, fillers and formulation auxiliary agents of all kinds.
Tablets, dragees, capsules, pills, granules, suppositories, solutions, suspensions and emul-sions, pastes, ointments, gels, creams, lotions, powders and sprays are mentioned as phar~ma-ceutical preparations. Tablets, dragees, capsules, pills and granules may contain in addition to the conventional excipients the active ingredient, such as (a) fillers and diluents, for example starches, lactose, cane sugar, glucose, mannitol and silicic acid, (b) binders, for example car-boxymethylcellulosis, alginate, gelatine, polyvinylpyrrolidone, (c) moisture-retaining agents, for example glycerol, (d) dispersing agents, for example agar-agar, calcium carbonate and sodium carbonate, (e) solution ret~arders, for example paraffin and (f) resorption accelerators, for example quaternary ammonium compounds, (g) wetting agents, for example cetyl alcohol, glycerol monostearate, (h) adsorption agents, e.g. kaolin and betonite and (i) lubricants, for example talcum, calcium and magnesium stearate and solid polyethylene glycol or mixtures of the substances listed under (a) to (i). The inventive compounds may furthermore be incor-porated into other carrier materials for example plastics, (plastics chains for topical therapy), collagen or bone cement.
The tablets, dragees, capsules, pills and granules may be provided with the conventional coatings and casings optionally comprising opaquing agents and may also be put together so that they release the active ingredient or active ingredients only or preferably in a specific part of the intestinal optionally with sustain release, wherein polymer substances and waxes for example may be used as embedding compounds.
The active ingredients may optionally also be present in microencapsulated form with one or more of the above mentioned excipients.
In addition to the active ingredients suppositories may also contain the conventional water soluble or water insoluble excipiems, for example polyethylene glycols, fats, for example ca-coa fat and higher esters (for example C~4- alcohol with Ci6-fatty acid) or mixtures of these substances.
In addition to the active ingredients ointments, pastes, creams and gels may contain the con-ventional excipients, for example animal and vegetable fats, waxes, paraffins, starch, traga-canth, cellulose derivative, polyethylene glycols, silicones, bentonites, silicic acid, Talc and zink oxide or mixtures of these substances.
In addition to the active ingredients powders and sprays may contain the conventional excipi-ents, for example lactose, talcum, silicic acid, aluminium hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays may additionally contain the con-ventional blowing agents, for example chlorofluorohydrocarbons.
In addition to the active ingredients solutions and emulsions may contain the conventional excipients such as solvents, solubilisers and emulgators, for example water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propyle-neglycol, 1,3-butyleneglycol, dimethylformamide, oils, in particular cotton seed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerol, glycerol formal, tetr~ahydrofurfuryl alcohol, polyethyleneglycols and fatty acid esters of sorbitan or mixtures of these substances.
The solutions and emulsions may also be present in sterile and blood isotonic form for paren-teral application.

In addition to the active ingredients suspensions may contain conventional excipients such as liquid diluents, for example water, ethyl alcohol, propylene glycol, suspending agents, for example ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, micro-crystalline cellulose, aluminium metahydroxide, bentonite, agar-agar and tragacanth or mix-tures of these substances.
The active ingredient or the active ingredients of the formulae (I) to (XI~
shall be present in the above mentioned pharmaceutical preparations, preferably in a concentration of approxi-mately 0.1 to 99, 5 weight %, preferably of approximately 0. 5 to 95 weight %
of the total mixture. The ratio of the substances to be individually combined is dependent on the individ-ual active ingredient. Therefore, ac,~tive agents are present, which are administered in a general dose of 0.1 mg/kg body weight per day (ibandronate and alendronate), 0.5 mg/kg body weight per day (mevastatin, simvastatin, pravastatin, fluvastatin), 10 mg/kg body weight per day (pamidronate).
In ~~~ition to the compounds of the formulae (I) to (XIV) and t~P inhibitors of lipid metabo-lism the above mentioned pharmaceutical preparations may also contain further pharmaceuti-cal active ingredients, such as antiviral, antiparasitic, antimycotic or antibacterial active agents.
The lipid metabolism inhibitors used according to the invention fiuther may contain sulfona-mide, sulfadoxin, artemisinin, atovaquon, chinin, chloroquine, hydroxychloroquin, mefloquin, halofantrin, pyrimethamine, armesin, tetracycline, doxycyclin, proguanil, metronidazol, praziquantil, niclosamide, mebendazol, pyrantel, tiabendazole, diethylcarbazin, piperazin, pyrivinum, metrifonate, oxamniqui,n, bithionol or suramin or several of these substances.
Preferably lovastatin, atorvastatin, simvastatin, mevastatin, pravastatin and fluvastatin are administered orally, wherein pravastatin and fluvastatin are administered in active form.
In general it has proved advantageous both in human and veterinary medicine to administer the active ingredient or ingredients of formulae (1) and (~ in total quantities of approximately 0.5 to approximately 600, preferably 1 to 200 mg/kg body weight per 24 hours, optionally in the form of several individual doses in order to achieve the desired results.
An individual dose contains the active ingredient or ingredients preferably in quantities of approximately 0.5 to approximately 200, in particular 1 to 60 mg/kg body weight. It may, however, be necessary to deviate from the above-mentioned dosages and this is dependent on the nature and the body weight of the patient to be treated, the nature and the severity of the disease, the nature and the method and the application of the pharmaceutical compositions as well as the time scale or interval within the administration takes place.

It has proved advantageous to administer the inhibitors of the lipid metabolism in the known range of dosage, which are known from the treatment of disorders of the lipid metabolism and the calcium and phosphate metabolism. These are total quantities of approximately 0.005 to approximately 200, preferably 0.01 to 100 mg/kg body weight per 24 hours, are optionally administered in the form of several individual doses in order to achieve the desired results. An individual dose contains the active iingredient or ingredients (inhibitors of the lipid metabo-lism) preferably in quantities of approximately 0.002 to approximately 50, in particular 0.01 to 10 mg/kg body weight. It may however be necessary to deviate from the above-mentioned dosages and this is dependent on the nature and the body weight of the patient to be treated, the nature and the severity of the disease, the nature and the method and the application of the pharmaceutical compositions as well as the time scale or interval within the administration takes place. With amino bisphosphonates it has to be considered that their resorbility is very low. This characteristic is advantageous in the case of an attack in the intestinal tract (for ex-ample in the case of amoebic dysentery). Here doses of up to 10 mg/kg body weight pamidro-nate are administered orally. For injection in general doses up to ? mg/kg body weight are sufficient.
Thus in some cases it may be sufficient to get by with less than the above mentioned quantity of active ingredient, whilst in other cases the above-stated quantity of active ingredient must be exceeded. The person skilled in t;he art may determine the optimum dosage and method of application of the active ingredient in each case by virtue of his expert experience.
The lipid metabolism inhibitors according to the invention may be administered in animals in the conventional concentrations and preparations together with the feed or feed preparations or the drinking water.
The lipid metabolism inhibitors many be administered simultaneously, separately or succes-sively.
Example Preparation anti-infectiously active agents Preparation for injection ( 1 ) The necessary quantity of the sterile anti-infectiously active agents, 500 mg ~-(N-acetyl-N-hydroxy amino)-propyl-phosphoric acid monosodium salt and 90 mg 3-amino-1-hydroxy-propyliden-1,1-bisphosphonic acid disodium salt are distributed on flasks or am-pules. The flasks are sealed hermetically for excluding bacteria. For injection it is taken in 500 ml physiologic solution of sodium chloride respectively and administered.

In principle in the same manner as describe above under (1) further injectable preparations of the anti-infectiously active agents ~~re prepared:
(2) 250 mg 3-(N-formyl-N-hydroxy amino~propylphosphonic acid -monosodium salt and 1 mg 3-methylpentylamino-1-hydroxypropylid~-1,1-bisphosphonic acid disodium salt are used for injections.
(3) 250 mg 3-(N-formyl-N-hydroxy amino)-traps-1-propenylphosphonic acid -monosodium salt and 90 mg 3-amino-1-hydroxypropyliden-1,1-bisphosphonic acid disodium salt are used as an active ingredient for injection.
Preparation of tablets:
A suitable tablet formulation is formed by the following mixture:
3-(N-formyl-N-hydroxy amino)-propylphosphonic acid -monosodium salt200 mg lovastatin 10 mg mannitol 400 mg starch SO mg magnesium stearate 10 mg Preparation of capsules 3-(N-formyl-N-hydroxy amino)-propylphosphonic acid monopotassium salt 300 mg simvastatin 10 mg magnesium stearate 15 mg The present ingredients are mixed and then filled into a hard gelatine capsule in usual manner.

Claims (23)

Claims

1. Combined preparation comprising as active ingredients at least one anti-infectiously active compound, which inhibits the 2-C-methylerythrose-4-metabolic pathway, and at least one inhibitor of the lipid metabolism, wherein the inhibitor of the lipid metabolism and the anti-infectiously active compound are not identical.

2. Combined preparation according to claim 1, characterized in that the inhibitors of lipid metabolism are selected from the group which consists of cholestyr amine, .beta.-sitosterol, colestipol, probucol, nicotinic acid, nicotinyl alcohol, clofibrin acid derivative and analogues of the clofibrin acid derivative, HMG-CoA-synthetase-inhibitors, HMG-CoA-reductase-inhibitors, squalene synthetase inhibitors and squalene monooxygenase inhibitors.

3. Combined preparation according to claim 2, characterized in that the inhibitors of lipid metabolism are inhibitors of the squalene synthetase, in particular pyrophosphates, pyrophosphate derivatives, bisphosphonic acid derivatives, phosphinylmethyl phosphoric acid derivatives, phosphinylformyl derivatives, phosphonocarboxyl derivatives, phosphonosulfonic acid derivatives, phosphinylmethylphosphonic acid derivatives.

4. Combined preparation according to claim 2, characterized in that the inhibitors of lipid metabolism are inhibitors of the HMG-CoA-reductase, in particular lovastatin, atorvastatin, mevastatin, simvastatin, fluvastatin, pravastatin and cerivastatin handelt.

5. Combined preparation according to claim 2, characterized in that the inhibitors of lipid metabolism are clofibrin acid derivative and their analogues, in particular gemfibrozil, fenofibrate, bezafibrate, clofibrate, ciprofibrate and clinofibrate.

6. Combined preparation according to claim 2, characterized in that the inhibitors of the lipid metabolism are bisphosphonic acid derivative, in particular clodron acid derivatives, etidron acid derivatives, pamidron acid derivatives, in particular pamidronat, ibandron acid derivatives, in particular ibandronate, alendron acid derivatives, in particular alendronate, zoledron acid derivatives, in particular zoledronat, risedron acid derivatives, tiludron acid derivatives and cimadron acid derivatives.

7. Combined preparation according to one of claims 1 to 6, comprising as an active ingredient at least one aminohydrocarbyl phosphoric acid derivative of the general formula (I) wherein R I1 and R I2 are the same or different and are selected from the group which consists of H, OH, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, and substituted and unsubstituted heterocyclic radical, R I3 and R I4 are selected from the group which consists of substituted and unsubstituted alkyl with 1 to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl with 1 to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl with 1 to 26 carbon atoms, substituted and unsubstituted alkynyl with 1 to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, X I3 and X I4, wherein X I3 and X I4 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl with 1 to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl with 1 to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl with 1 to 26 carbon atoms, substituted and unsubstituted alkynyl with 1 to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, a silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids,, and A I represents an alkylene radical, alkenylene radical or hydroxyalkylene radical or corresponds to the following formula (IA):

wherein one or more the carbon atoms, selected from the group C I3, C I4, C
I5, together with their substituents also may be absent, and at least one present substituent out of B1 to B10 is a C3-8-cycloalkyl-(C0-9)-alkyl group, wherein the C3-8-cycloalkyl group as well as the C0-9-alkyl group may comprise one or more double bonds and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms and wherein the cycloalkyl group as well as the alkyl group may be substituted with hydroxy, halogen, amino, oxo groups, with branched or straight C1-9-alkyl groups and C2-9-alkenyl groups, wherein the C1-9-alkyl groups and C2-9-alkenyl groups may be substituted with hydrogen, hydroxy, amino, halogen and oxo groups, and the remaining present substituents B I1 to B I10 are selected from the group which consists of hydrogen, hydroxy-, halogen-, amino groups, C1-26-alkyl radicals, C1-26-alkoxy radicals, C1-26-alkoxy-C1-26-alkyl radicals or both substituents a C-Atoms together form an oxo group , wherein each C1-26-alkyl radical and each C1-26-alkoxy radical may be branched or straight and saturated or unsaturated with one or more double bonds and may be substituted with hydroxy, amino, halogen and oxo groups.

8. Combined preparation according to one of the claims 1 to 6, comprising as an active ingredient at least one bisphosphonic acid according the general formula wherein X I11, X I12, X I13, X I14, which are the same or different, are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, metals of the 1., 2. and 3. main group of the periodic systems, such as Na, K, Ca, Mg, Al as well as substituted and unsubstituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids, A II which also may be absent is selected from the group which consists of alkylene, alkenylene and hydroxyalkylene, R II1, R II2, which are the same or different, are selected from the group which consists of H, OH, -NH2, substituted and unsubstituted aryl, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical and -SR II3m, Cl and NR II4R II4, wherein RII3, R II4, which are the same or different, are selected from the group which consists of H, OH, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted cycloalkyl and substituted and unsubstituted heterocyclic radical, or their pharmaceutically acceptable salts, esters as well as salts of esters or compounds, which upon application provide the compounds to be administered as metabolic products or decomposition products.

9. Combined preparation according to one of claims 1 to 6, comprising as an active ingredient at least one compound of the general formula (III):

wherein R III1 is selected from the group which consists of H, substituted and unsubstituted aryl, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen and OX III1, wherein X III1 is selected from the group which consists of hydrogen, substituted and unsubstituted aryl, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, a silyl, substituted and unsubstituted heterocyclic radical, a ration of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds, R III4 and R III3 are the same or different and are selected from the goup which consists of hydrogen, substituted and unsubstituted aryl, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen and OX III4 and OX III3, wherein X III4 and X III3 are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted cycloalkyl, a silyl, substituted and unsubstituted heterocyclic radical, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids,, and A III1 and A III2, out of which one or both may be absent, are the same or different and represent a alkylene radical, alkenylene radical, an oxo radical, a hydroxy radical or oxo hydroxyalkylene radical.

10. Combined preparation according to one of the claims 1 to 6, comprising as an active ingredient at least one compound the general formula (IV):

in which R IV1 and R IV2 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyaakyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen, OX IV1 and OX IV2, wherein X IV1 and X IV2 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, B IV selected from the group which consists of the ether group (IVA) wherein A IV1 and A IV2, out of which A IV2 also may be absent, are the same or different and are selected from the group which consists of alkylene radical, alkenylene radical and hydroxyalkylene radical, the keto group (IVB) wherein A IV3 and A IV4, out of which one or both also may be absent, are the same or different, are selected from the group which consists of alkylene radical, alkenylene radical and hydroxyalkylene radical, and 5 and 6 membered cyclic, in particular heterocyclic compounds, which contain beside carbon at least one heteroatom as a ring member, wherein the heteroatom is selected from the group which consists of oxygen and nitrogen, R IV3 and R IV4 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl having up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl having up to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl having up to 26 carbon atoms, substituted and unsubstituted alkynyl having up to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OX IV3 or OX IV4, wherein X IV3 or X IV4 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl having up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl having up to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl having up to 26 carbon atoms, substituted and unsubstituted alkynyl having up to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, a Silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids, and their pharmaceutically acceptable salts, esters and amides and salts of esters.

11. Combined preparation according to one of the claims 1 to 6, comprising as an active ingredient at least one phosphoric acid derivative of the general formula (V):

wherein A V1 and A V2, out of which one or both may also be absent, are the same or different and are selected from the group which consists of an alkylene radical, an alkenylene radical and a hydroxyalkylene radical, and preferably the carbon chain -A V1-CHOH-A V2-consists of 2 to 5 carbon atoms, particularly preferably of 3-4 carbon atoms, B V is selected from the group which consists of a radical of the formula (VA) wherein R V1 is selected from the group which consists of hydrogen, OH, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical and halogen, a radical of the formula (VB) wherein R V2, R V3 and R V4 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen, and a radical of the formula (VC) wherein R V5, R V6 and R V7 are the same or different and are selected from the group which consists of hydrogen, OH, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen, wherein X V2 or X V4 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, a silyl, a ration of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids,, and their pharmaceutically acceptable salts, esters and amides and salts of esters.

12. Combined preparation according to one of the claims 1 to 6, comprising as an active ingredient at least one compound of the general formula (VI):
wherein R V13 and R V14 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl having up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl having up to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl having up to 26 carbon atoms, substituted and unsubstituted alkynyl having up to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OX V13 or OX V14, wherein X V13 or X V14 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl having up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl having up to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl having up to 26 carbon atoms, substituted and unsubstituted alkynyl having up to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, a silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids, and B VI is selected from the group which consists of the group (VIA) and the group (VIB) R VII-N=A VI- (VIB) wherein A VI is selected from the group which consists of an alkyleneamine radical, an alkenyleneamine radical, a hydroxyalkyleneamine radical, an alkyleneimine radical, an alkenyleneimine radical and a hydroxyalkyleneimine radical, wherein the nitrogen atom is a member of the chain, which connects the phosphorus atom with the nitrogen atom of the group or the group R VII-N=, and wherein R VII and R VI2 in group (VIA) are the same or different and R VII and R VI2 in group (VIA) and R VII in group (VIB) are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen, OX VII
and OX VI2, wherein X VI1 and X VI2 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, or their pharmaceutically acceptable salts, esters and amides and salts of esters.

13. Combined preparation according to one of the claims 1 to 6, comprising as an active ingredient at least one compound tile general formula (VII):
in which A VII selected from the group which consists of a (C1-9)-alkylene radical, which may contain one or more double bonds and may be substituted with hydroxy, halogen, amino, oxo groups, with branched or straight C1-9-alkyl groups and C2-9-alkenyl- groups, wherein the C1-9-alkyl groups and C2-9-alkenyl groups may be substituted with hydrogen, hydroxy, amino, halogen and oxo groups, -C-O-C- and -C-N-C-, wherein the carbon atoms of -C-O-C- and -C-N-C- may be substituted with an alkyl having up to 7 carbon atoms or hydroxy groups, or in which A VII corresponds to the following formula (VIA):
wherein one or more carbon atoms, selected from the group C VII3, C VII4, C
V115, together with their substituents may be absent, arid at least one present substitute of B
VII1 to B VII10 is a C3-8-cycloalkyl-(C0-9)-alkyl group, wherein the C3-8-cycloalkyl group as well as the C0-9-alkyl group may comprise one or more double bonds and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms, and wherein the cycloalkyl group as well as the alkyl group may be substituted with hydroxy, halogen, amino, oxo groups with branched or straight C1-9-alkyl groups and C2-9-alkenyl groups, wherein the C1-9-alkyl groups and C2-9-alkenyl groups may be substituted with hydrogen, hydroxy, amino, halogen and oxo groups, and the remaining present substituents B VII1 to B VII10 are selected from the group which consists of hydrogen, hydroxy, halogen, amino groups, C1-26-alkyl radicals, C1-26-alkoxy radicals, C1-26-alkoxy-C1-26-alkyl radicals or both substituents of one C-atom together form an oxo group, wherein each C1-26-alkyl radical and each C1-26-alkoxy radical is branched or straight and saturated or unsaturated with one or more double bonds and may be substituted with hydroxy, amino, halogen and oxo groups, wherein R VII1 selected from the group which consists of 5 and 6 membered heterocycles with one or two nitrogen, oxygen or sulfur atoms in the ring, wherein the heterocycle may be saturated or unsaturated with one or more double or triple bond and may be substituted with hydroxy, halogen, amino, oxo groups and with branched or straight C1-9-alkyl groups and C2-9-alkenyl groups, wherein the C1-9-alkyl groups and C2-9-alkenyl groups may be saturated or unsaturated with one or more double or triple bonds and may be substituted with hydrogen, hydroxy, amino, halogen and oxo groups, wherein R VII3 and R VII4 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted C1-26-alkyl, hydroxy-C1-26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-26-alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OX VII3 and OX VII4, wherein X VII3 and X VII4 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted C1-26-alkyl, substituted and unsubstituted hydroxy-C1-26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-26-alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, a silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids, and their pharmaceutically acceptable salts, esters and amides and salts of esters.

14. Combined preparation according to one of the claims 1 to 6, comprising as an active ingredient at least one compound of the general formula (VIII):
wherein the wavy line represents a bond, which either has .alpha.- or .beta.-configuration, n is 0 or 1, wherein RVIII11 is selected from the group which consists of substituted and unsubstituted C1-26-alkyl, hydroxy-C1-26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-26-alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen and OX VIII11, wherein X VIII11 is selected from the group which consists of hydrogen, substituted and unsubstituted C1-26-alkyl, substituted and unsubstituted hydroxy-C1-26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-26-alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, a silyl, a canon of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids,, R VIII1 is selected from the group which consists of C1-24-alkyl radicals, C2-24-alkenyl radicals, C2-241-alkapolyenyl radicals containing 2 to 6 double bonds, C2-24-alynyl radicals, C3-8-cycloalkyl radicals, C3-8-cycloalkyl-C1-24-alkyl radicals and C1-12-alkoxy-C1-12-alkyl radicals, R VIII2, R VIII3 and R VIII4 each are selected independently from the group which consists of hydrogen, halogen, amino, acetylamino, azido and XR VIII6-groups, wherein X is O or S and R VIII6 is selected from the group which consists of a hydrogen radical, branched or straight C1-4-alkyl radicals and C2-4-alkenyl radicals, wherein the C1-4-alkyl radicals as well as the C2-4-alkenyl radicals may be optionally substituted with hydrogen, amino, halogen or oxo groups, or R VIII2, R VIII3 and R VIII4 together with the respective geminal hydrogen group represent an oxo group, R VIII5 selected from the group which consists of hydrogen, C1-24-alkyl groups, C3-8-cycloalkyl radicals, Ar(C1-24-alkyl) groups, aryl groups, Acyl groups, heterocyclic radicals, halogen, wherein all radicals may be branched or straight and may be optionally be substituted with hydroxy, amino, halogen or oxo group and may contain 2 to 6 double and triple bonds or R VIII5 is a phenyl radical the formula VIVA or XIIIB, wherein R VIII7 and R VIII8 are the same or different and are bound to any two positions of the phenyl ring and each are selected independently from the group which consists of hydrogen, halogen, C1-4-alkyl radicals, C1-4-alkoxy radicals, formyl, acetyl, propionyl, butyryl radicals, formyl, acetyl, propionyl, butyryloxy radicals, C2-5-alkoxycarbonyl radicals, which all may be branched or straight, or R7 and R VIII8 may form together a straight saturated alkylene chain with 3 to 4 carbon atoms, which are bound to adjacent positions, for example the 2,3-positions or the 3,4-positions of the phenyl ring, or R7 and R8 together form a methylenedioxy radical, a 1,1-ethylidenedioxy radical or a 1,2-ethylenedioxy radical, which is bound to the 2,3- or 3,4-positions of the phenyl ring, or R VIII5 is selected from the group which consists of R VIII9COOCHR VIII10- and R VIII9OCOOCHR VIII10-, wherein R VIII9 is selected from the group which consists of C1-6-alkyl radicals, C2-6-alkenyl radicals, C2-6-alkynyl radicals, C3-8-cycloalkyl radicals, C3-8-cycloalkyl-C1-6-alkyl radicals and C1-6-alkoxy-C1-6-alkyl radicals, wherein all radicals may be branched or straight and may be optionally substituted with hydroxy, amino, halogen or oxo groups, and R10 is a branched or straight C1-4-alkyl radical, and wherein the configurations of the substituents R VIII2, R VIII3, R VIII4 and R VIII5OOCPO(OH)OCH2- in (VIII) is independently selected from D-gluco, L-gluco, D-galacto, L-galacto, D-manno, L-manno, D-talo, L-talo, D-allo, L-alto, D-altro, L-altro, D-gulo, L-gulo, D-ido or L-ido are, if n is 1 or the configurations of the substituents R2, R3 and R5OOCPO(OH)OCH2-in I are independently D-ribo, L-ribo, D-arabino, L-arabino, D-xylo, L-Xxylo, D-lyxo or L-lyxo, if n is 0.

15. Combined preparation according to one of the claims 1 to 6, comprising as an active ingredient at least one compound the general formula (IX) wherein R IX11 is selected from the group which consists of substituted and unsubstituted C1-26-alkyl, hydroxy-C1-26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-26-alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen and OX IX11, wherein X IX11 is selected from the group which consists of hydrogen, substituted and unsubstituted C1-26-alkyl, substituted and unsubstituted hydroxy-C1-26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-26-alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, a silyl, a canon of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids,, wherein R IX1 and R IX2 each are selected independently from the group which consists of C1-24-alkyl radicals, C3-8-cycloalkyl radicals, C3-8-cycloalkyl-C1-24-alkyl radicals, C1-24-alkoxy radicals, C1-24-alkylthio- radicals, C1-24-alkoxy-C1-24-alkyl radicals and C1-24-alkylthio-C1-24-alkyl radicals, acyl radicals, aryl radicals, aralkyl radicals, heterocyclic radicals, halogen and hydrogen, and each C1-24-alkyl radical and C1-24-alkoxy radical may be branched or straight and saturated or unsaturated with 2 to 6 double bonds and optionally may be substituted with hydroxy, amino, mercapto, halogen, oxo groups or C1-24-alkoxy radicals, C1-24-alkylcarbonyloxy radicals, C1-24-alkoxycarbonyloxy radicals, C1-24-alkylthio radicals, C1-24-alkylcarbonylthio radicals, C1-24-alkylamino radicals, di-(C1-24-alkyl)amino radicals, C1-24-alkylcabonylamino radicals, C1-24-alkyl-(C1-24-alkylcarbonyl)amino radicals, C1-24-alkoxycarbonylamino radicals or C1-24-alkyl-(C1-24-alkoxycarbonyl)amino radicals, wherein each aralkyl radical, heterocyclic radical, C1-24-alkyl radical and C1-24-alkoxy radical may be branched or straight and saturated or unsaturated with 2 to 6 double bonds or triple bonds, or wherein R IX1-CH-CH-R IX2 form a part a C4-8-carbon ring, which optionally may be substituted with hydroxy, mercapto, amino, halogen, oxo groups or with C1-24-alkyl radicals, C1-24-alkoxy radicals, C1-24-alkylthio radicals, C1-24-alkylamino radicals, Di-(C1-24-alkyl)amino- radicals, C1-24-alkylcabonyl radicals, C1-24-alkylcarbonyloxy radicals, C1-24-alkoxycarbonyl radicals, C1-24-alkylcarbonylthio radicals or C1-24-alkylcarbonylamino radicals, C1-24-alkyl-(C1-24-alkylcarbonyl)-amino radicals, wherein each C1-24-alkyl radical may be branched or straight and saturated or unsaturated with 1 to 6 double bonds, or wherein R IX10 is a branched or straight C1-4-alkyl radical, and wherein R IX1-CH-CH-R IX2 form a part of the furanose or pyranose ring of a sugar, e.g.
D-ribose, D-arabinose, D-xylose, D-lyxose, D-glucose, D-galactose, D-mannose, D-talase, D-allose, D-altrose, D-gulose, D-idose or the respective L-isomers, wherein the hydroxy groups each optionally may be substituted with hydrogen, amino, azido, oxo, mercapto radicals or C1-24-alkoxy radicals, C1-24-alkylthio radicals, C1-24-alkylamino radicals, di-(C1-24-alkyl)amino radicals, C1-24-alkylcabonyloxy radicals, C1-24-alkylcarbonylthio radicals, C1-24-alkylcarbonylamino radicals, C1-24-alkyl-(C1-24-alkylcarbonyl)amino radicals, wherein each C1-24-alkyl radical may be branched or straight and saturated or unsaturated with 1 to 6 double bonds, and their pharmaceutically acceptable salts, esters and amides and salts of esters as well as their optical isomers.
R IX1 and R IX2 each in particular may be selected independently from the group which consists of carboxyl radicals, carboxamido radicals, aryl radicals, aryloxycarbonyl radicals, aryl-C1-24-alkyl radicals, C1-24-alkoxycarbonyloxy radicals, C1-24-alkylaminocarbonyl radicals, di-(C1-24-alkyl)-aminocarbonyl radicals, aryl-C1-24-alkoxycarbonyl radicals, aryl-C1-24-alkylaminocarbonyl radicals, C1-24-alkylcabonyloxy-(C1-4)alkylmethoxycarbonyl radicals, C1-24-alkoxy-carbonyloxymethoxycarbonyl radicals, C1-24-alkoxycarbonyl-oxy-(C1-4-alkyl)-methoxycarbonyl, wherein each C1-24-alkyl radical may be branched or straight and saturated or unsaturated with 2 to 6 double bonds, and each C1-4-alkyl radical and C1-24-alkoxy radical may be branched or straight and saturated or unsaturated, and each aryl radical of the formula IXA
wherein R IX3 and R IX4 are the same or different and each are selected from the group which consists of hydrogen, halogen, C1-4-alkyl radicals, C1-4-alkoxy radicals, formyl, acetyl, propionyl, butyryl radicals, formyl, acetyl, propionyl, butyryloxy radicals, C1-4-alkoxycarbonyl radicals, which all may be branched or straight, or R IX3 and R IX4 together form a straight saturated alkylene chain with 3 to 4 carbon atoms, which are bound to adjacent positions of the phenyl ring or R IX3 and R IX4 together form a methylenedioxy radical, a 1,1-ethylidendioxy radical or a 1,2-ethylenedioxy radical, which is bound to adjacent positions of the phenyl ring.

16. Combined preparation according to one of the claims 1 to 6, comprising as an active ingredient at least one compound of the general formula (X):
wherein R X1 is selected from the group which consists of hydrogen, substituted and unsubstituted C1-9-alkyl, substituted and unsubstituted hydroxy-C1-9-alkyl, substituted and unsubstituted C1-9-alkenyl, substituted and unsubstituted C1-9-alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen and OX X1, wherein X X1 selected from the group which consists of hydrogen, substituted and unsubstituted C1-9-alkyl, substituted and unsubstituted hydroxy-C1-9-alkyl, substituted and unsubstituted C1-9-alkenyl, substituted and unsubstituted C1-9-alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, wherein R X2 is selected from the group which consists of C1-26-alkyl radicals, C1-26-alkoxy radicals, C1-26-alkoxy-C1-26-alkyl- radicals, C3-8-cycloalkyl-(C0-26)-alkyl radicals, wherein one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms, each C3-26-alkyl radical and each C3-26-alkoxy radical branched or straight and each C3-8-cycloalkyl radical, each C2-26-alkyl radical and each C2-26-alkoxy radical may be saturated or unsaturated with one or more double bonds and each C3-8-cycloalkyl- radical, each C1-26-alkyl radical and each C1-26-alkoxy radical may be substituted with hydroxy, amino, halogen and oxo groups or by the carbyl group COR X3, wherein R X3 is selected from the group which consists of substituted and unsubstituted C1-26-alkyl, hydroxy-C1-26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-26-alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen and OX X3, wherein X X3 are selected from the group which consists of hydrogen, substituted and unsubstituted C1-26-alkyl, substituted and unsubstituted hydroxy-C1-26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-26alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, a silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids.

17. Combined preparation according to one of the claims 1 to 6, comprising as an active ingredient at least one compound of the general formula (XI):
wherein Z XI is a phosphorus atom or a sulfur atom, in which A XI is a straight C2-9-alkylene chain with substituents which are the same or different and are selected from the group which consists of hydrogen, hydroxy, halogen, amino and oxo groups, C1-26-alkyl radicals, C1-26-alkoxy radicals, C1-26-alkoxy-C1-26-alkyl radicalsorC3-8-cycloalkyl-(C0-9)-alkyl radicals, wherein each C1-26-alkyl radical and each C1-26-alkoxy radical may be branched or straight and saturated or unsaturated with one or more double bonds and may be substituted with hydroxy, amino, halogen and oxo groups and the C3-8-cycloalkyl group as well as the C0-9-alkyl group of the C3-8-cycloalkyl-(C0-9)-alkyl group may contain one or more double bonus and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms, and wherein the cycloalkyl group as well as the alkyl group may be substituted with hydroxy, halogen, amino, oxo groups, with branched or straight C1-9-alkyl groups and C2-9-alkenyl groups wherein the C1-9-alkyl groups and C2-9-alkenyl groups may be substituted with hydrogen, hydroxy, amino, halogen and oxo groups, in which R XI1 and R XI2 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted C1-9-alkyl, substituted and unsubstituted hydroxy-C1-9-alkyl, substituted and unsubstituted C1-9-alkenyl, substituted and unsubstituted C1-9-alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen, OX XI1 and O XI2, wherein X XI1 and X XI2 are the same or different and selected from the group which consists of hydrogen, substituted and unsubstituted C1-9-alkyl, substituted and unsubstituted hydroxy-C1-9-alkyl, substituted and unsubstituted C1-9-alkenyl, substituted and unsubstituted C1-9-alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, in the R XI3 and R XI4 are the same or different and are selected from the group which consists of substituted and unsubstituted C1-26-alkyl, hydroxy-C1-26-aryl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-26-alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OX XI3 and O XI4, wherein X XI3 and X XI4 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted C1-26-alkyl, substituted and unsubstituted hydroxy-C1-26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-26-alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, a silyl, a ration of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids,, and their pharmaceutically acceptable salts, esters and amides and salts of esters.

18. Combined preparation according to one of the claims 1 to 6, comprising as an active ingredient at least one compound the general formula (XII):
wherein A XII is selected from the group which consists of hydrogen, substituted and unsubstituted C1-28-alkyl radicals, substituted and unsubstituted alkoxy-(C0-28)-alkyl radicals, substituted and unsubstituted cycloalkyl-(C0-28)-alkyl radicals, substituted and unsubstituted cy-~~
cloalkoxy-(C0-28)-alkyl radicals, substituted and unsubstituted amino-(C0-28)-alkyl radicals and substituted, unsubstituted thio-(C0-28)-alkyl radicals and substituted or unsubstituted Acyl-(C0-28)-alkyl radicals and halogen, wherein each alkyl radical, each alkoxy radical and each aryl radical may be branched or straight and each alkyl radical, each alkoxy radical, each aryl radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms, R XII3 selected from the group which consists of hydrogen, substituted and unsubstituted alkyl groups, substituted and unsubstituted alkoxy-(C0-26)-alkyl radicals, substituted and unsubstituted C3-14-cycloalkyl-(C0-26)-alkyl radicals, substituted and unsubstituted cycloalkoxy-(C0-26)-alkyl radicals, substituted and unsubstituted amino-(C0-26)-alkyl radicals, substituted and unsubstituted silyl-(C0-26)-alkyl radicals and substituted and unsubstituted thio-(C0-26)-alkyl-groups, wherein each alkyl radical and each alkoxy radical may be branched or straight and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms, or a carbon chain of two C-atoms in A XII forms a ring together with R XII3 such that an isoxazolidone ring is formed, and R XII4 is selected from the group which consists of hydrogen; substituted and unsubstituted alkyl radicals, substituted and unsubstituted aryl radicals and substituted and unsubstituted cycloalkyl-(C0-26)-alkyl radicals, wherein each alkyl radical and each aryl radical may be branched or straight and each alkyl radical, each aryl radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms.

19. Combined preparation according to one of the claims 1 to 6, comprising as an active ingredient at least one compound the general formula (XIII):
wherein n is an integer from 0 to 4, and wherein R XIII1, R XIII2, R XIII3, R XIII4, R XIII5 and R XIII6 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl radicals, substituted and unsubstituted alkoxy radicals, substituted and unsubstituted acyl radicals, substituted or unsubstituted cycloalkyl-(C0-26)-alkyl radicals, substituted and unsubstituted cycloalkyl-(C0-26)-alkoxy radicals and halogen, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or straight and each alkyl radical, each acyl radical, each alkoxy radical and each cyclo-(C0-26)-aryl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms.

20. Combined preparation according to one of the claims 1 to 6, comprising as an active ingredient at least one compound of the general formula (XIV):
wherein Y XIV is a C1-3-alkenylene group, which is optionally substituted with the substituents R XIV1 and R XIV2 and optionally substituted with the substituents R XIV3 to R
XIV6, wherein R XIV1 to R XIV8 are the same or different and are selected from the group which consists of hydrogen, hydroxy, halogen, substituted and unsubstituted alkyl groups, substituted and unsubstituted cycloalkyl-(C0-26)-alkyl radicals, substituted and unsubstituted cycloalkoxy-(C0-26)-alkyl radicals, substituted and unsubstituted alkoxy-(C0-26)-alkyl radicals, substituted and unsubstituted amino groups and substituted, unsubstituted thio-(C0-26)- alkyl radicals, substituted and unsubstituted sulfonyl-(C0-26)-alkyl radicals, substituted and unsubstituted sulfinyl-(C0-26)-alkyl radicals and substituted or unsubstituted acyl radicals, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or straight and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms and R XIV13 and R XIV14 are defined the same as R XIV1 to R XIV8 or together form an oxo group, wherein Z XIV represents the organophosphorus group wherein R XIV9 and R XIV10 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted (C1-26)-alkyl groups, substituted and unsubstituted hydroxy-(C1-26)-alkyl radicals, substituted and unsubstituted cycloalkyl-(C0-26)-alkyl radicals, substituted and unsubstituted acyl, halogen, OX XIV9 or OX XIV10, wherein each alkyl radical, each alkoxy radical and each acyl radical branched or straight and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms, wherein X XIV9 or X XIV10 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted (C1-26)-alkyl groups, substituted and unsubstituted hydroxy-(C1-26)-alkyl radicals, substituted and unsubstituted cycloalkyl-(C0-26)-alkyl radicals, substituted and unsubstituted acyl a silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or straight and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms, or wherein Z XIV represents the amino group wherein R XIV11 and R XIV12 are the same or different and are selected from the group which consists of hydrogen, substituted and unsubstituted alkyl groups, substituted and unsubstituted cycloalkyl-(C0-26)-alkyl radicals, substituted and unsubstituted cycloalkoxy-(C0-26)-alkyl radicals, substituted and unsubstituted alkoxy-(C0-26)-alkyl radicals and substituted or unsubstituted acyl radicals, wherein each alkyl radical, each alkoxy radical and each aryl radical branched or straight and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur atoms, wherein B XIV is selected from the group which consists of substituted and unsubstituted C1-26-alkenylene groups, wherein one C-atom may be replaced by one oxygen atom and one C-atom by one sulfur atom or two C-atoms may be replaced by a S-hetrocycle and wherein each alkenylene radical may be branched or straight and saturated or unsaturated with one or more double or triple bonds and may be substituted with one or more hydroxy groups, halogen groups or oxo groups.

21. Use of lipid metabolism inhibitors according to one of the proceeding claims for the therapeutic and prophylactic treatment of infectious processöes in humans, animals and plants and as herbicides in plants.

22. Use according to claim 21, characterized in that the infectious processes are caused by unicellular or multicellular parasites, fungi, bacteria or viruses.

23. Use according to claim 21 or claim 22, characterized in that the processes are infectious processes in humans or animals.