GB2243158A

GB2243158A - Detoxification using micro-organisms

Info

Publication number: GB2243158A
Application number: GB9106663A
Authority: GB
Inventors: Derek Clifford Ellwood; James Henry Peter Watson
Original assignee: Bio Separation Ltd
Current assignee: Bio Separation Ltd
Priority date: 1990-04-02
Filing date: 1991-03-28
Publication date: 1991-10-23
Also published as: GB9007378D0; GB9106663D0

Abstract

A pharmaceutical composition comprising an anaerobic micro-organism and a physiologically acceptable inorganic compound capable of being converted by the micro-organism into an insoluble product which is deposited on the micro-organism and grows to form a cluster; the cluster being capable of adsorbing toxins. Preferably the micro-organism is Desulphovibrio. Micro-organisms and compounds such as iron (II) solphate as hereinbefore described for use in a therapeutic method for removal of a toxin from the human or animal gut or bloodstream and for use in the manufacture of a medicament for therapy by removal of a toxin from the human or animal gut or bloodstream.

Description

DETOXIFICATION USING MICRO-ORGANISMS The present invention relates to the detoxification of the human or animal gut or bloodstream by microorganisms. It also relates to micro-organisms and inorganic compounds which promote detoxification by such microorganisms and to their use.

When toxins such as heavy metals are ingested there is a need to prevent them becoming absorbed from the gut into the bloodstream and other body fluids. Although it has been found that the equilibrium concentration of heavy metals in body fluids is only 1/10,000 of the concentration in the gut, even this small proportion of a heavy metal can cause serious toxic effects, especially if the heavy metal is radioactive or otherwise very toxic. There is therefore a need to immobilise heavy metals and other toxins which are present in the gut and promote their rapid excretion from the system in order to minimise their absorption into body fluids.Similarly, after a heavy metal or other toxin has been absorbed into the bloodstream there is a need to remove it as efficiently as possible, and this may be done by promoting its excretion into the gut if a way can be found of effectively binding it in the gut so as to prevent reabsorption.

The present invention provides compositions useful for the removal of toxins from the human or animal gut or bloodstream. Such compositions are preferably usable without specialist medical knowledge and without the use of complex specialist equipment so as to provide therapy at a minimal cost.

When Desulphovibrio is grown in the presence of iron (II) sulphate the latter is reduced to insoluble iron sulphide by the Desulphovibrio. The iron sulphide produced is deposited on the Desulphovibrio and grows to form a cluster which has a microcrystalline structure, a high surface area and contains embedded Desulphovibrio cells. It has been found that such Desulphovibrio clusters are able to absorb toxins such as heavy metals, chloro- and fluorocarbons, polychlorobiphenyls and insecticides from the medium in which they are placed.

Desulphovibrio is an anaerobic bacterium which occurs naturally in the colon of many, though not all, humans. When it is present it is believed to provide a naturally detoxifying mechanism in the way just explained.

However, if a person has little or no Desulphovibrio, or even if he or she has a normal population, promotion of the detoxifying mechanism provides a way of removing toxins present in the colon. This result may be achieved, for example, by administering both Desulphovibrio and iron (II) sulphate, so that they can reach and become active in the colon. Alternatively if the patient does have sufficient Desulphovibrio then growth of the naturally occurring Desulphovibrio may be prompted by administering iron (II) sulphate only. In either case the toxins are removed by the natural excretion of the clusters onto which they are absorbed.

Furthermore, toxins may be removed from the bloodstream by a mass action effect once they are removed from the colon.

One advantage of the use of this method to promote the formation of clusters containing naturally occurring Desulphovibrio, is that it will discourage the entry of toxins into the bloodstream via free (unclustered) Desulphovibrio on which toxins are deposited.

While it is preferable to use Desulphovibrio and iron (II) sulphate, the invention is not limited to these species; any anaerobic micro-organism and any physiologically acceptable inorganic compound which form an insoluble cluster may be used in the process described above.

The present invention therefore provides a pharmaceutical composition comprising an anaerobic microorganism and a physiologically acceptable inorganic compound capable of being converted by the micro-organism into an insoluble product which is deposited on the micro-organism and grows to form a cluster; the cluster being capable of adsorbing toxins.

Preferably the micro-organism occurs naturally in the human or animal gut. Use of such naturally occurring micro-organisms may promote natural processes for the removal of toxins and reduce any possible side effects from the introduction of a foreign species into the gut.

The composition may comprise a micro-organism which is dead or alive. Preferably however, the micro-organism is alive and may then multiply within the gut. Preferably the inorganic compound is therefore also a promoter for the growth of the micro-organism. The composition may comprise other ingredients to promote growth of the micro-organism, for example other micro-organisms.

The detoxifying micro-organism is preferably Desulphovibrio. Any species of Desulphovibrio may be used, although naturally occurring species are preferred.

The inorganic compound is preferably a physiologically acceptable sulphate, phosphate or carbonate and most preferably a sulphate. In particular when Desulphovibrio is used iron (II) sulphate is preferably employed.

Preferably the composition comprises trace essential elements such as Zn and Co. Such trace elements may be used to supplement any which are removed by the detoxification process.

According to a specific embodiment the anaerobic micro-organism may be attached to magnetic beads. The beads may for example be made of polyacrylate and contain, preferably are coated with, magnetite to render them magnetic. If the gut area is then subjected to a magnetic field this serves to increase the retention time of the magnetic beads in the gut and therefore of the anaerobic micro-organism in the gut. The magnetic field may be applied for instance by means of a magnetic belt worn by the patient.

The compositions according to the present invention may be for administration by any known method. Specifically they may be for oral administration in the form of capsules.

Such capsules are preferably resistant to the acidic environment of the stomach so as to allow the micro-organism to reach the colon without being degraded in the stomach.

Alternatively such compositions may be administered rectally by for instance an enema.

As a further aspect of the invention there is provided a composition as hereinbefore described for use in a therapeutic method for the removal of a toxin from the human or animal gut or bloodstream.

The invention also provides an anaerobic microorganism as hereinbefore described, for use in such a therapeutic method.

The present invention also provides a physiologically acceptable inorganic compound, as hereinbefore described, capable of being converted by an anaerobic micro-organism into an insoluble product which is deposited on the micro-organism and grows to form a cluster; the cluster being capable of adsorbing toxins; which compound is for use in such a therapeutic method. Such compounds may be useful for administration alone to promote removal of toxins by a micro-organism already present in the colon of the patient. Optionally the compound may be used in a composition of any known form, in combination with trace essential elements.

As another further aspect of the invention there is provided a combination comprising an anaerobic microorganism as hereinbefore described, and a physiologically acceptable inorganic compound as hereinbefore described, capable of being converted by the micro-organism into an insoluble product which is deposited on the micro-organism and grows to form a cluster, the cluster being capable of adsorbing toxins; which combination is for use in the manufacture of a medicament for therapy by removal of a toxin from the human or animal gut or bloodstream.

The invention also provides an anaerobic microorganism, as hereinbefore described, for use in such manufacture.

The invention also provides a physiologically acceptable inorganic compound, as hereinbefore described, capable of being converted by an anaerobic micro-organism into an insoluble product which is deposited on the microorganism and grows to form a cluster; the cluster being capable of adsorbing toxins; which compound is for use in such manufacture. Such compounds may be useful for administration alone to promote removal of toxins by a micro-organism already present in the colon of the patient.

Such a compound may be used in combination with trace essential elements.

As yet a further aspect of the invention there is provided a pack for simultaneous, sequential or separate use comprising a pharmaceutical composition comprising an anaerobic micro-organism, as hereinbefore described; and a pharmaceutical composition comprising a physiologically acceptable inorganic compound, as hereinbefore described, capable of being converted into an insoluble product which is deposited on the micro-organism and grows to form a cluster; the cluster being capable of adsorbing toxins.

According to a specific embodiment of the invention a composition comprising Desulphovibrio and iron (II) sulphate is provided. The iron (II) sulphate acts to promote detoxification by Desulphovibrio. Alternatively iron (II) sulphate may be provided to promote detoxification by Desulphovibrio naturally occurring in the colon.

It has been shown that iron (II) sulphate is converted by Desulphovibrio to insoluble iron sulphide.

This is then deposited on the Desulphovibrio and forms a micro-crystalline structure of high surface area (up to 400m2/gram). The iron sulphide deposit grows and forms a cluster up to 100 microns across and containing up to 104 Desulphovibrio cells embedded in it. The iron (II) sulphate also acts to promote growth of the Desulphovibrio by providing energy from the reduction of sulphate to sulphide.

The growth of the Desulphovibrio may be further promoted by the presence of other ancilliary micro-organisms.

In such clusters Desulphovibrio may convert soluble toxins to produce insoluble products which are then adsorbed onto the iron sulphide. Other toxins may simply be adsorbed by the cluster without any chemical conversion. The toxins are then removed from the gut by the natural excretion of the cluster.

It has been shown that such clusters may be used to remove from solution heavy metal toxins which include U, Ru, Sr, Co, Pu, Am, Ce, Cs, Zr, Pt, Pd, Rh, Ir, Au, Ag, Fe, Ni, Cu, Hg, and Cd. With the exception of Ir and Cs it has been possible to reduce the metal ion concentrations from 10 ppm to at least 1-2 ppb and in many cases less than 1 ppb. In the case of Cs the reduced effectiveness may be caused by relative increased solubility of the metal sulphide produced by the Desulphovibrio. It has also been possible to reduce concentrations of chloro- and fluoro-carbons by a factor of 100 by using a combination of Desulphovibrio and iron (II) sulphate.

Other potentially toxic materials such as pesticides and herbicides are also removed from the gut by the clusters.

The dosage of iron (II) sulphate or other physiologically acceptable inorganic compound as aforesaid may be the same as the dosages which have previously been used with such compounds for other clinical indications.

Typically from 0.5 to 2.0g per day of hydrated iron (II) sulphate may be administered in divided doses, or an equivalent amount of the anhydrous salt.

Administration of iron (II) salts often causes the faeces to turn black (because of the presence of black iron (II) sulphide) but this black colour disappears after about 7 - 8 days presumably because Desulphovibrio and other sulphate-reducing bacteria have been removed from the gut.

When this happens suitable sulphate-reducing bacteria should be supplied to the subject, preferably in a capsule which dissolves in the lower bowel.

Claims

1. A pharmaceutical composition comprising an anaerobic micro-organism and a physiologically acceptable inorganic compound capable of being converted by the microorganism into an insoluble product which is deposited on the micro-organism and grows to form a cluster; the cluster being capable of adsorbing toxins.

2. A composition according to claim 1 in which the micro-organism is one which occurs naturally in the human or animal gut.

3. A composition according to claim 1 or 2 in which the micro-organism is alive.

4. A composition according to claims 1, 2 or 3 in which the inorganic compound is capable of promoting growth of the micro-organism.

5. A composition according to any one of the preceding claims in which the micro-organism is Desulphovibrio.

6. A composition according to any one of the preceding claims in which the inorganic compound is an inorganic sulphate, phosphate or carbonate.

7. A composition according to claim 6 in which the inorganic compound is iron (II) sulphate.

8. A composition according to any one of the preceding claims comprising trace essential elements.

9. A composition according to any one of the preceding claims in which the micro-organism is attached to - magnetic beads.

10. A composition according to any one of the preceding claims in the form of a capsule resistant to the acidic environment of the stomach.

11. A composition according to any one of the preceding claims for use in a therapeutic method for removal of a toxin from the human or animal gut or bloodstream.

12. A composition according to claim 1 which is substantially as hereinbefore described.

13. A combination for use in the manufacture of a medicament for therapy by removal of a toxin from the human or animal gut or bloodstream, comprising an anaerobic microorganism and a physiologically acceptable inorganic compound capable of being converted by the microorganism into an insoluble product which is deposited on the micro-organism and grows to form a cluster; the cluster being capable of adsorbing toxins.

14. A combination according to claim 13 comprising a micro-organism as defined in any one of claims 1, 2, 3, 5, or 9 and an inorganic compound as defined in any one of claims 1, 4, 6 or 7.

15. A combination according to claim 13 or 14 which comprises trace essential elements.

16. An anaerobic micro-organism, capable of reacting with a physiologically acceptable inorganic compound to produce an insoluble product which is deposited on the micro-organism and grows to form a cluster; the cluster being capable of adsorbing toxins; for use in a therapeutic method for removal of a toxin from the human or animal gut or bloodstream.

17. An anaerobic micro-organism, capable of reacting with a physiologically acceptable inorganic compound to produce an insoluble product which is deposited on the micro-organism and grows to form a cluster; the cluster being capable of adsorbing toxins; for use in the manufacture of a medicament for removal of a toxin from the human or animal gut or bloodstream.

18. A micro-organism according to claim 16 or 17 which is as defined in claim 1, 2, 3, 5 or 9.

19. A micro-organism according to claim 16 or 17 which is substantially as hereinbefore described.

20. A physiologically acceptable inorganic compound capable of being converted by an anaerobic micro organism into an insoluble product which is deposited on the micro-organism and grows to form a cluster, the cluster being capable of adsorbing toxins; for use in a therapeutic method for removal of a toxin from the human or animal gut or bloodstream.

21. A physiologically acceptable inorganic compound capable of being converted by an anaerobic microorganism into an insoluble product which is deposited on the micro-organism and grows to form a cluster; the cluster being capable of adsorbing toxins; for use in the manufacture of a medicament for removal of a toxin from the human or animal gut or bloodstream.

22. A inorganic compound according to claim 20 or 21 which is as defined in claims 1, 4, 6 or 7.

23. An inorganic compound according to claim 20 or 21 which is substantially as hereinbefore defined.

24. A pack, for simultaneous, sequential or separate use, comprising a pharmaceutical composition comprising an anaerobic micro-organism and a pharmaceutical composition comprising a physiologically acceptable inorganic compound capable of being converted into an insoluble product which is deposited on the micro-organism and grows to form a cluster; the cluster being capable of adsorbing toxins.

25. A pack according to claim 24 in which the micro-organism is as defined in claim 1, 2, 3, 5, or 9 and the inorganic compound is as defined in claim, 4, 6 or 7.