GB1575940A - Heteropolyanion compounds containing tungsten combined with antimony - Google Patents

Abstract

The heteropolyanion compounds of formulae II and VI, as well as those of formula III whose symbols M and M' are defined in Claim 8, are therapeutically useful by virtue of their antiviral activity. The compounds of formulae II and VI are obtained by adding a solution containing the Sb(III) ion to a solution of ammonium or potassium tungstate, and by collecting the precipitate. The compounds of formula III are obtained by treating the compound of formula II with an aqueous solution containing an alkali metal ion or alkaline-earth metal ion other than sodium. <IMAGE>

Description

(54) HETEROPOLYANION COMPOUNDS CONTAINING TUNGSTEN COMBINED WITH ANTIMONY (71) We, AGENCE NATIONALE DE VALORISATION DE LA RECHERCHE (ANVAR), a body corporate organised under the laws of France of 13, rue Madeleine Michelis 92522 Neuilly Sur Seine, France, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: The invention relates to novel heteropolyanion compounds containing tungsten combined with antimony.

The invention also relates to processes for producing such compounds. The novel compounds are useful as active agents in the treatment of viral infections in humans and non-human animals as well as of pathological processes due to viruses.

The invention also relates to pharmaceutical compositions containing a therapeutically effective amount of at least one of said compounds.

U.K. patent specification no. 1,487,397 relates to sodium-containing heteropolyanions possessing anti-viral properties, in particular a compound of tungsten, antimony and sodium denoted by the reference HPA 23.

In general to prepare the compound HPA 23 in the form of its ammonium salt, an aqueous solution containing the Sb"' ion is reacted hot with a 1 M solution of sodium tungstate and the reaction medium is kept substantially at neutrality by the addition of concentrated ammonium hydroxide in a sufficient amount to make the medium colourless, which results in the precipitation of the desired ammonium salt which is recovered by filtration and subsequently treated in the usual manner.

The reaction temperature is less than the boiling temperature of the reaction medium, for example in the vicinity of 80"C. The aqueous solution containing the Sb"' ion is advantageously prepared by dissolving SbCI3 in a saturated solution of NH4CI.

As later studies have shown, the product HPA 23 is a heteropolyanion corresponding to the formula: [Na Sb9 W21 086] 18 In the form of its ammonium salt, the product has the formula: [Na SbgrW21 O,,] (NH4)18, and it can be in various forms, notably a hydrate with 8 molecules of water.

The present invention relates to a novel type of heteropolyanion and compounds containing the latter in which the position of the sodium atom of the compound HPA 23 is vacant or occupied by other metallic ion. The invention also relates to such compounds in their metallic form, that is to say the form of their salts with metals or with ammonium.

According to a first aspect, the invention relates therefore to a novel general class of heteropolyanions of the formula (I) [M Sb9 W2, O88]n- (I) in which M can be absent or represent an alkali metal or alkaline-earth metal, other than sodium, and n is equal to 19 if M is absent, or to 19-p, ifp is the charge of M in the form of its ion. The overall negative charge of the ion is hence equal to 19.

The polyion (I) can notably be isolated in the solid state in the form of its ammonium salt of formula (II) [Sb9 W21 86] (NH4)ts (Il) The IR spectrum of the compound (II) is shown in Figure 1 which has been divided into Figures la and lb for convenience of presentation (concentration 6/600 mg, phase KBr, apparatus Perkin-Elmer 225).

To prepare compound (II) an aqueous solution of ammonium tungstate is taken to which is added hot (60-80 C) a solution of Sb2O3 in HCl (or SbCl2 in saturated NH4CI), the addition of concentrated ammonia then causing, after removal of an insoluble part, the precipitation of the desired ammonium salt.

The aqueous solution of ammonium tungstate is prepared by reacting tungstic anhydride W03 at boiling temperature with ammonia.

The molar proportions to be respected between W03 and Sb203 are 4.5 to 5 moles of WO3 per mole of Sb203.

Other compounds containing the heteropolyanion of formula (I) correspond to Formula (III) [M Sb9 W21 86] N'18 (III) in which formula M represents an alkali metal or alkaline-earth metal other than sodium, such as potassium, calcium or magnesium and Mis an alkali metal such as cesium, rubidium or potassium or alkaline-earth metal, such as calcium or barium, or again ammonium or quartenary ammonium.

In particular, the invention relates to a novel heteropolyanion corresponding to the formula (IV) [K Sb9 W2, O86] 18 (IV) This novel product may be considered as a 9-antimonio-III-2l-tungsto-VI- potassium compound. It can occur as such or in the form of ammonium or metal salts, in particular of the alkali or alkaline-earth metals. A typical example is the ammonium salt of formula: [K Sb9 W21 O86] (NH4)19 (V) Another particularly advantageous example is the potassium salt of the heteropolyanion (IV), this salt corresponding to the formula (VI) [K Sb9 W21 O86] K19 (VI) The compound (VI) decomposes above 340"C. Its IR spectrum is shown in Figure 2 of the accompanying drawings, which has been divided into Figures 2a and 2b for convenience of presentation.

The IR spectrum obtained has been produced on a Beckmann IR--12 spectrophotometer with a KBr pastille.

The Raman spectrum of the compound (VI) is shown in Figure 3. The following data were used: compound (VI) in powder form 5145 A 400 mW interference filter PM 720 V resolution 4 cm-' speed 50 cm-'/min Coderg PHO Spectrometer The polyanion (II) can be supplied as such in the form of the distilled water solution. The polyanionic structure is however unstable in the presence of metallic ions in aqueous solution and this observation enables the preparation according to a first process of other compounds according to the invention. In this regard it will be noted that the compound HPA 23 described in U.K patent specification no.

1,487,397 can be obtained by the treatment of the polyanion (II) in aqueous solution by means of an 0.5 M solution of NaCI.

The compound (V) can be obtained from the polyanion (II) by treatment of the latter in aqueous solution by means of a solution of CKI, for example 0.5 M.

Other compounds according to the invention can be prepared in similar manner by the treatment of the polyanion (II) by means of a solution of a salt of the metal that it is desired to introduce into the ionic structure. By way of example, there may be mentioned the compound of magnesium obtained by treatment of the polyanion (II) with a solution of 0.5 M MgCI2.

Of course, the compounds according to the invention can also be prepared by direct synthesis, as will be illustrated by the following examples.

The invention products can exist in the form of numerous hydrates. All the hydrated forms of said products fall within the scope of the present invention.

The polyanion (IV) is composed of a central bicyclic cavity formed of Sb-O-W-O-Wb chains having at its centre a K+ ion. Around this cavity exist other atoms of W and Sb, the overall ratio r=W/Sb being in the vicinity of 2.4.

The invention relates also to all the isomeric forms of the heteropolyanion concerned. It relates also to mixtures obtainable by conversion of heteropolyanion compounds under the influence of variations in the pH and in the nature of the solutions in which they are placed.

As has been previously noted, the heteropolyanion (II) is not stable in aqueous solution. To stabilise it, it should be placed in aqueous solution in the presence of metallic ions which are introducible inside the complex, these ions being preferably sodium, potassium, magnesium or calcium ions.

In aqueous medium containing potassium ions, in particular a dilute aqueous solution of potassium chloride, the heteropolyanion (II) provides compound V (ammonium salt).

The HPA 23 compound can also be subjected to an ionic exchange reaction in the course of which the potassium takes the place of the sodium and ammonium ions. This can be carried out simply by dissolving the compound HPA 23 in a concentrated aqueous solution of potassium chloride.

In this way a mixture of the compound HPA 23, (V) and (VI) is obtained.

It is advantageous, however, to prepare the compound (VI) by a direct process starting from SbCl3, KCI and K2WO4.

According to this process, a first solution is prepared, containing the Sb"' ion, by dissolving SbCI3 hot in a saturated aqueous solution of KCI, said first solution is added to a second solution consisting of an aqueous solution of K2WO4, the reaction temperature being from 6090 C, in particular about 80"C, and at the end of the reaction a saturated solution of potassium bicarbonate is introduced until the reaction medium is colourless and its pH is about 7.

The compound (VI) precipitates in the course of the reaction and continues to deposit during cooling. For purification, the precipitate is filtered, then washed with a solution of KCI, for example 0.5 molar, and finally recrystallised in distilled water.

The proportions of the constituents of the reaction are selected so that the heteropolyanion corresponding to the compound (VI) is obtained. To this end, I part by weight of SbCl3 is used per 3.4 parts of K2WO4. For example, an aqueous molar solution of K2WO4 is used and the corresponding amount of SbCI3 must be dissolved in the saturated KCI solution, is calculated.

The following examples illustrate the invention without being in any way limiting.

EXAMPLE 1.

Preparation of [Sb9 W;, O,,] (NH4)19: compound of formula (II) An aqueous solution of ammonium tungstate is prepared by reacting at boiling temperature 81 g of tungstic anhydride (WO3) with NH3 (1 liter of 1.2 molar ammonia).

To this solution, is added gradually at 800 C, a solution obtained by dissolving 21.8 g of antimony trioxide (Sb2O3) in 100 ml of 6 M HCI.

At the end of the operation, about 20 ml of 12 M NH3 are added. An insoluble precipitate forms and it is filtered hot rapidly. The ammonium salt [Sb9 W21 66] (NH4)as crystallises in the course of cooling from the supernatent solution.

The crystals obtained are filtered and then washed with a saturated solution of NH4Cl.

EXAMPLE 2.

Preparation of the compound [K Sb9 W2, O86]K,8: compound of formula (VI) A solution containing 12.2 g of SbCI3 dissolved hot in 50 ml of a saturated solution of KCI is added gradually to 125 ml of an aqueous molar solution of K2WO4 previously brought to 800 C. At the end of the operation, about 20 ml of a saturated solution of potassium bicarbonate is added, so that the mixture is colourless and its pH close to 7.

The potassium salt of the heteropolyanion precipitates in the course of the preparation and continues to deposit during cooling. The precipitate is filtered and then washed with a solution of 0.5 molar KCI and finally recrystallised in distilled water. In this way about 25 g of the compound (VI) of the formula indicated above are obtained. Its IR and Raman spectra are shown in Figures 2 and 3 respectively.

The present invention relates also to the application of the compounds of formulas (II) and (III), in particular the compound (VI), denoted below by the abbreviated reference HPA 39, in the form of a pharmaceutical composition suitable for the preventive and curative treatment of viral infections in humans and non-human animals and of the pathological processes due to viruses. Thus, the invention also relates to pharmaceutical compositions containing., as active agents, the heteropolyanion (III) compounds, in particular the compound HPA 39, in association with pharmaceutically acceptable vehicle. In a particular embodiment, the pharmaceutical compositions according to the invention are conditioned in injectable form, for example in aqueous solution (physiological solution) at a pH in the neighbourhood of neutrality, for injection into a human or a non-human.

In the first pharmacological tests reported below, the heteropolyanion applied is the product of formula (VI) denoted by the abbreviated reference HPA 39. The activity of HPA 39 was compared with the sodium compound of the formula [Na Sb9 W21 099] (NH4)19, the latter compound being denoted by the abbreviation HPA 23. The tests were applied to the treatment of viruses of Friend's leukemia.

Pharmacological Tests In the experiments, DBA2 mice, male or female, aged from 2 to 3 months, of a weight close to 20 g were used.

A polycythemia strain of Friend's virus (VFP) was used maintained for some years in the laboratory. The viral stock was constituted by an acellular supernatent liquid obtained by centrifugation of ground leukemic spleens, formed in a 0.5 M PBS-saccharose solution. Titration of the stock was done in vivo, according to the method of Reed and Muench (American Journal of Hygiene 1938, 27, 493497).

The measurement was expressed as SD50 ("Spleen enlarging dose 50%").

Experimental Procedure: The Friend's virus was injected in the mouse by the intraperitoneal route. The animal then developed a characteristic splenomegaly. Death appearing three weeks after the viral innoculation, at the doses normally employed, the animals were sacrificed on the 21st day after infection, for study of the splenomegaly. The spleens were taken out and then weighed individually. Any spleen whose weight exceeded 250 mg was considered as pathological. The HPA 23 and HPA 39 heteropolyanions were diluted usually in physiological serum or distilled water.

They were administered like the virus by the intraperitoneal route in a single dose or in repeated doses at times varied with respect to the viral innoculation period. results: 1. Protective Effect of HPA 39 against Friend's Leukemia.

Table 1 below summarises the results of two consecutive experiments wherein the mice, innoculated with 20 SD50 of VFP, received a single dose of HPA 39 ranging from 0.5 mg to 2 mg, the same day as the virus.

The survival percentage was established on the 62nd day after the viral injection.

2. Study of the Response to HPA 39 as a function of the Innoculated Viral Dose.

From the point of view of the splenomegaly, a study was made of the effect of a single injection of 2 mg of HPA 39 in the case where the animals were innoculated with increasing doses of VFP ranging from 5 to 50 SD50 per animal.

The results are summarised in the following Table II.

3. Test of Treatment of Friend's Leukemia by Repeated Injections of HPA 39.

In this experiment, animals previously innoculated with 20 SD50 of VFP were used. The effect of 5-day treatments comprising one daily injection of 0.5 mg of HPA 39, were studied.

Day 0 (Do) being the day of infection, three periods were selected: from D + 3 to D + 7, from D + 10 to D + 14, from D + 17 to D + 21. In order to know the stage of the disease at the beginning of each treatment, 10 control animals were sacrificed on days +10 and +17.

In parallel, the toxicity of this treatment on non-leukemic animals was studied.

Although the short-term toxicity seems very low, it should be noted that, 60 days after the end of the treatment, 50% of these animals died.

Table III below gives the average value of the spleen weight 21 days after infection, as well as the average weight of the spleens at the beginning of each treatment.

4. Comparative Test of HPA 23 and HPA 39 on Splenomegaly induced by the VFP.

Table IV below summarises the results obtained with a single injection of 1 mg of each of these products on the splenomegaly induced by VFP 21 days after the injection of 20 SD50.

TABLE 1.

Effect of HPA 39 on Friend's Leukemia: Average weight Limiting Survival Dose HPA 39 of spleens (g) values % Toxicity injected D+21 (g) D+21 (*) 0 exp 1 = 1.349 0.4022.63 NF exp2=0.897 0.390l.598 40 40 0.5 mg per exp 1 = N.F. N.F. NF mouse 0 IP exp 2 = 0.711 0.221 # 2.036 70 1 mg per exp 1 = 0.322 0.252 # 0.443 NF mouse 0 IP exp 2 = 0.258 0.190 # 0.348 100 2 mg per exp 1 = 0.308 0.225 # 0.405 NF mouse 0 IP exp2=0.262 0.208 < 0.291 100 * The toxicity represents the percentage of mortality in lots of 10 non-leukemic animals treated with a dose as indicated.

TABLE II.

Dose-effect Relationship of HPA 39 with respect to VFP Viral HPA 39 Limiting Innoculum injected Average Spleen Values (IP) (mg IP) Weights (g) (g) 5SD90 0 0.619 0.228 # 1.552 2 0.253 0.158 # 0.310 10 SD50 0 0.726 0.3230.979 2 0.269 0.160 # 0.331 20 SD50 0 1.052 0.239 # 1.989 2 0.409 0.233 < 0.412 50 SD50 0 1.651 1.328#2.180 2 0.350 0.113 < 0.721 TABLE III Effect of HPA 39 in the Treatment of Friend's Leukemia Average Spleen Period of Weight at the Average Spleen Limiting Treatment beginning of Weight (g) Values (5x0.5 mg) the Treatment D + 21 (g) 0 1.202 0.408 # 2.594 D + 3 # D + 7 not done 0.610* 0.204l.577 D + 10 # D + 14 0.240 0.656* 0.250 # 1.250 D + 17 # D + 21 0.500 0.532** 0.263#0.988 * The increase in weight of the spleen manifests the continuing development of the leukemia.

** Arrest of the leukemia.

TABLE IV.

Comparative Anti-viral Effect of HPA 23 and HPA 39: structure-activity relationship Treatment Average Spleen Limiting (1 mg - IP) Weight Values (g) 0 1.426 0.740#2.063 HPA 23 0.320 0.222#0.391 HPA 39 0.294 0.259 # 0.335 The results reported in Table IV show that the products HPA 23 and HPA 39 result in a very marked reduction in splenomegaly, which demonstrates their effectiveness in inhibiting the development of Friend's leukemia. In addition, HPA 39 manifests an activity higher than that of HPA 23.

As a whole, the above results make it evident that HPA 39, administered to mice infected with Friend's leukemia virus, show no effect of toxicity. HPA 39 arrests the development of the leukemia: thus, a dose of 2 mg of HPA 39 per mouse permits, for 100% of the infected mice, survival up to the 62nd day, the day at which they were sacrificed.

An advantageous property of the product HPA 39 has also been established, namely that this product possesses a synergic action when it is administered at the same time as interferon. To prove this synergy of HPA-interferon, four groups of mice were used and the products tested were administered under the following conditions: Interferon: pre-treatment 6 hours before infection - intraperitoneal route 5000 U/mouse.

HPA 39: 3 mg/mouse - intraperitoneal route immediately after the innoculation of the virus.

Encephalomyocarditis virus of the mouse - 50 lethal dose/mouse; innoculation subcutaneous route (SC) Group I: 10 mice received the virus and served as controls Group II: 10 mice received interferon and, 6 hours afterwards, the virus Group III: 10 mice received the virus by the SC route and HPA 39 by the intraperitoneal route Group IV: 10 mice received interferon and then, 6 hours afterwards, the virus and HPA 39.

Results on the 15th Day Mortality Group I: Control 8/10 Group II: Interferon alone 8/10 Group III: HPA 39 alone 8/10 Group IV: HPA 39 + interferon 3/10 The results recorded above show clearly the superiority of the HPA 39interferon association with respect to the results obtained with one of the substances alone.

Other "in vivo" tests were carried out to test various products according to the invention and various comparison products of the prior art for their preventive action against Friend's virus-induced leukemia in the DBA-2 mouse (according to the technique described above).

By way of comparison HPA 23 and two organic cryptates were tested: Cryptofix 222 (Merck) : formula C19H39N309 (MW: 376) Cryptofix 211 (Merck) : formula C14H29N3O6 (MW: 288.35) To groups of ten DBA 2 mice previously innoculated with Friend's virus, were administered each of the products described in the dose of 1 mg per mouse. The control group only received the virus.

The mice were sacrificed 21 days after the innoculation of the virus. The spleens were taken out and then weighed individually. Each spleen weighing more than 250 mg was considered as leukemic. The results of these experiments are assembled in Table V. As this Table shows, all the products according to the invention are capable of reducing in the mouse, splenomegaly induced by Friend's virus, although the known cryptates are inactive, and even toxic.

In addition, the compound (VI) of HPA 39 is more active than HPA 23.

Further pharmacological tests were performed for testing the in vivo activity of the HPA 39 compound.

1. FRIEND'S LEUKEMIA Friend's leukemia is induced in a DBA2 mouse by the polycythemiant strain of virus.

The criteria selected to follow the development of the disease were splenomegaly and survival.

The animals were sacrificed 21 days after injection of the virus. The spleens were taken out and weighed individually.

Effect of HPA 39 on Splenomegaly As shown in Table VI, HPA 39, injected in a single dose by the intraperitoneal route the same day as the virus (20 SD50), considerably reduced splenomegaly. In this experiment, the doses ranged from 1 to 5 mg. These three doses had substantially the same activity. It is noted, however, that there is a certain toxicity at 5 mg.

Table VII summarises an experiment where HPA was tested, under the same conditions as previously, against increasing doses of virus. It is clear that, whatever the viral innoculum, HPA 39 preserves all its activity.

Effect of HPA 39 on Survival The survival was followed of groups of animals (20) innoculated by 20 Sod90 of virus and treated the same day, by a single dose of HPA 39 or 0.5,1, and 2 mg.

The median survival of the control group was 56 days, that of the group treated by 0.5 mg, 128 days, that of the group treated by 1 mg, 151 days, and finally, that of the group treated by 2 mg, 108 days.

200 days after the beginning of the experiment, 25% of the animals treated by I or 2 mg were still living.

Time of Action of HPA 39 Table VIII shows the results of treatment tests by HPA 39 on splenomegaly.

The animals all received Do of the experiment, 20 SD50 of Friend's virus. In the first part of the Table, tests of sequential treatments of 5 injections of 0.5 mg per day of HPA 39 are reported.

Under these conditions, HPA 39 preserves notable activity on splenomegaly, but less important than after a single injection of the substance the same day as the virus. In the second part of Table VIII, tests of the effect of a single dose of 2 mg of substance injected on different days with respect to the viral innoculation are reported.

Only one injection 2 days after the virus preserved a certain effectiveness, but however the protection level obtained is less than that obtained on injections effected the same day as the virus.

Effect of HPA 39 on the Intrasplenic Virus Ratio Compared were the virus ratio on the spleen of the control animals with that found in the spleen of the animals treated at Do by a dose of HPA 39. Although the treated animals had a spleen weight very much less than the controls, the virus level is comparable in the two groups. The technique used had been the S+L-- titration of ground spleen.

II. ENCEPHALOMYOCARDITIS The effect of HPA 39 on the lethal effect of encephalomyocarditis virus in the mouse was also treated.

Strains V77 L3 and S3 (passage in the culture for the strain L3 and in vivo for the strain S3), VR129 L3 and S3 were used.

The substance was injected in a single dose (3 mg) by the intraperitoneal route 30 minutes before the innoculation of 50 LD50 of virus which, itself, is done by the subcutaneous route.

A distinct increase in the number of animals surviving was observed relative to the control animals which had not received an injection of HPA 39.

TABLE V Activity of the Products on Friend's Leukemia "In Vivo"

Average Spleen Weight Treatment Process of 21 days after Infection Limiting Values Toxicity of (1 mg/mouse i.p.) Preparation (g) (g) the Product 0 (control) 1.426 # 0.561 0.740 0 2.063 Cryptofix 222 synthesised (2) 1.3417 # 0.700 0.3983 # (comparison) 2.200 Cryptofix 211 synthesised 1 animal surviving +++ (comparison) 1.6439 Polyanion (1) Polyanion (II) 0.342 # 0.097 0.243 0 (II) + 0.573 distilled water HPA 23 synthesised 0.310 # 0.050 0.222 0 (comparison) 0.391 HPA 23 Polyanion (II) 0.312 # 0.082 0.174 0 (comparison) + 0.415 0.5 M NaCl HPA 39 synthesised 0.294 # 0.022 0.259 0 (Polyanion VI) 0.335 Polyanion (V) Polyanion (II) 0.263 # 0.030 0.205 0 + 0.291 0.5 M KCl Polyanion Polyanion (II) 0.400 # 0.094 0.266 0 with Mg + 0.602 0.5 M MgCl2 (1) Polyanion (II) signifies the polyanion [Sb9 W21 O86] (NH4)19 in solution in distilled water, the metal M being absent.

(2) synthesised: signifies a compound prepared by direct synthesis as opposed to the similar compound prepared by treatment of the Polyanion (II) by means of a solution containing a metallic ion such as K or Mg.

TABLE VI Effect of HPA 39 on the Splenomegaly Induced by Friend's Virus

Average Weight of Spleen # Limiting Mortality type devistion Values % Spleens Treatment Number of Mice D0 # D+21 (g) (g) > 0.250 g 0 10 0 1.349 # 0.790 0.235 90% (control) 2.636 1 mg 9 0 0.324 # 0.060 0.252 100% 1.436 2 mg 10 0 0.308 # 0.053 0.225 90% 0.405 5 mg 10 3 to D+7 0.286 # 0.043 0.237 70% 0.315 TABLE VII HPA 39 : Effect on Splenomegaly Induced by Different Doses of Friend's Virus

Friend's Average Weight Limits Virus HPA 39 of Spleen (g) (g) 0 0.619 + 0.427 0.228 1.551 5 SD50 2 mg 0.253 + 0.043 0.158 0.310 0 0.697 i 0.268 0.318 1.120 10 SD50 2 mg 0.269 + 0.050 0.160 0.331 0 1.102 # 0.644 TABLE VIII HPA 39 : Effect of Various Treatments on Splenomegaly Induced by Friend's Virus

Average Weight of Spleen + type Limiting Treatment Dose Deviation (g) Values 0 1.202 # 0.643 0.488 - 2.5943 D+3 @ D+7 5 x 0.5 mg 0.610 # 0.440 0.204 - 1.577 D+10 - D+14: 5 x 0.5 mg 0.658 + 0.299 0.250 - 1.250 D+17 - D+21 5 x 0.5 mg 0.532 # 0.289 0.263 0.988 0 1.438 # 0.550 0.727 - 2.493 Do 2 mg 0.244 + 0.040 0.185 - 0.308 D-7 2 mg 1.488 # 0.443 0.762 - 2.033 D-4 2 mg 1.827 # 0.304 1.221 - 2.170 D~2 2 mg 1.668 + 0.569 0.764 - 2.233 D+2 2 mg 0.560 + 0.378 0.202 - 1.270 D+4 2 mg 1.179 # 0.548 0.257 - 1.748 D+7 2 mg 1.170 + 0.740 0.390 - 2.402

Claims (29)

WHAT WE CLAIM IS:

1. Heteropolyanion having the formula (I) [M Sb9 W21 O86] n- (I) in which M can be absent or can represent an alkali metal or alkaline-earth metal, other than sodium, and n is equal to 19 if M is absent, or to 19-p, ifp is the charge of the M in the form of its ion.

2. A compound having a heteropolyanion according to claim 1, corresponding to the formula (II) [Sb9 W21 O86] (NH4)18 (II) whose IR spectrum is shown in Figure 1.

3. A compound having a heteropolyanion according to claim 1, corresponding to the general formula (III) [M Sb9 W21 O86] M'18 (III) in which M is an alkali metal or alkaline-earth metal, other than sodium, and M' is an alkali metal or alkaline-earth metal or ammonium or quaternary ammonium.

4. A heteropolyanion according to claim 1, corresponding to the formula (IV) [K Sb9 W21 O86]18- (IV) in particular when present in the form of its ammonium salt of the formula (V) [K Sb9 W21 86] (NH4),9 (V)

5. Compound having the heteropolyanion specified in claim 4, corresponding to the formula (VI) [K Sb9 W21 O,,] K19 (VI) having a decomposition temperature of 340"C and whose IR and Raman spectra are shown in Figures 2 and 3 respectively.

6. Compounds according to any one of claims 2 to 5 in the form of hydrates.

7. Process for producing the compound (II) as defined in claim 2 of the formula: [Sb9 W21 O8F] (NH4),9, comprising taking an aqueous solution of ammonium tungstate, adding thereto a solution of antimony trioxide Sb203 in HCI or a solution of SbCl3 in NH4CI, then finally adding concentrated ammonia, causing the precipitation of the desired ammonium salt.

8. Process according to claim 7, wherein the aqueous solution of ammonium tungstate is prepared by reacting tungstic anhydride W03 at boiling temperature with ammonia.

9. Process according to claim 7, wherein the reaction temperature is situated between 60"C and boiling temperature.

10. Process according to claim 9, wherein the reaction temperature is about 80"C.

11. Process according to claim 7, wherein 4.5 to 5 moles of WO3 are used per mole of Sb2O3.

12. Process for producing the compound (VI), as defined in claim 5, of the formula [K Sb9 W31 O86] K19, or comprising preparing a first solution, containing the SbIII ion, by dissolving SbCl3 hot in a saturated aqueous solution of KCl, adding said first solution to a second solution consisting of an aqueous solution of K2WO4, the reaction temperature being from 60 100 C, and introducing at the end of the reaction a saturated potassium bicarbonate solution, until the reaction medium is colourless and its pH is in the vicinity of 7.

13. Process according to claim 12, wherein the reaction temperature is about 80"C.

14. Process according to claim 12, wherein 1 to 3.4 parts of SbCI3 are used with respect to an aqueous molar solution of KiWO

15. Process for producing compounds of formula (III), as defined in claim 3, comprising treating the compound of formula II in aqueous solution containing an alkali metal or alkaline-earth metal ion such as K, Ca or Mg, for example a salt such as KCI or MgCL2.

16. A pharmaceutical composition comprising the heteropolyanion specified in claim 1.

17. A pharmaceutical composition comprising compound (VI) as defined in claim 5.

18. A pharmaceutical composition according to claim 16, suitable for the preventive or curative treatment of viral infections in humans and non-human animals and of pathological processes due to viruses.

19. A pharmaceutical composition according to claim 18, suitable for the preventive or curative treatment of leukemia and sarcomas.

20. A pharmaceutical composition suitable for the preventive or curative treatment of viral infections in humans and non-human animals and of pathological processes due to viruses, including leukemias and sarcomas, containing a therapeutically effective amount of at least one compound according to claim 1.

21. A pharmaceutical composition according to claim 20 wherein said compound is compound (VI) as defined in claim 5.

22. A pharmaceutical composition according to claim 20, comprising a pharmaceutically acceptable vehicle.

23. A pharmaceutical composition according to claim 16, suitable for administration at the same time as interferon.

24. A pharmaceutical composition according to claim 16, containing also a synergically effective amount of interferon.

25. Method for the preventive or curative treatment of viral infections and of pathological processes due to viruses including leukemias and sarcomas in nonhuman animals, comprising administering a therapeutically effective amount of a novel compound according to claim !.

26. Heteropolyanion compounds according to claim I substantially as described hereinbefore with particular reference to Example I or Example 2 or Figures la and lb, Figures 2a and 2b, or Figure 3 of the accompanying drawings.

27. A process for producing a heteropolyanion compound according to claim I substantially as described hereinbefore with particular reference to Example I or Example 2.

28. A pharmaceutical composition substantially as described hereinbefore with particular reference to the pharmacological tests.

29. A method for the preventive or curative treatment of viral infections and pathological processes in non-human animals substantially as described hereinbefore with particular reference to the pharmacological tests.