AU1856200A

AU1856200A - Utilisation of capsules containing one or more antigenic substances for the prevention and/or treatment of autoimmune diseases

Info

Publication number: AU1856200A
Application number: AU18562/00A
Authority: AU
Inventors: Hans-Jurgen Hahn; Hans-Werner Heinrich; Udo Meyer
Original assignee: Bioserv AG
Current assignee: Bioserv AG
Priority date: 1998-11-27
Filing date: 1999-11-19
Publication date: 2000-06-19
Also published as: CA2352487A1; EP1135107A1; JP2002531391A; DE19854749A1; WO2000032168A1

Description

I 6Use of capsules containing one or more antigenic substances for prevention and/or treatment of auto-immune diseases The invention relates to the use of capsules, in particular micro-capsules, in which one or more antigenic substances are enclosed, in order to maintain the condition of immuno tolerance in organisms and also to prevent and/or treat auto immune diseases. Since recognition of the fact that a vitamin deficiency causes the origin of diseases at the latest, there has been agreement that the quantitative and qualitative composition of nutrition has a decisive influence on health. Alongside an absolute deficiency due to a generally reduced absorption of essential components of nutrition (e.g. hunger), a similar condition can also be observed in long-term alterations of nutrition habits (absolute deficiency of essential components in calorifically sufficient nutrition). Auto-immune diseases such as insulin-dependent diabetes (IDDM), multiple sclerosis and rheumatoid arthritis are characterised by a destruction of body-inherent parenchymatous cells by body inherent immune cells. On the basis of a genetic strain and caused by exogenous stimuli (environment), an over-proportional increase of auto-immune diseases has been observed in the course of the last few decades, with the result that the importance of these diseases for health politics and doctors working with the health insurance schemes has permanently grown. For example, morbidity of 1.5% has been calculated for IDDM in industrial nations. In the USA, Japan and the EU, a total of about 11.5 million patients with IDDM can be presupposed, causing enormous costs for their entire life with an average manifestation age of 16 years. It is currently assumed that the number of pre-diabetics, i.e. candidates with the potential risk of suffering form IDDM, can be identically high. For other auto-immune diseases, in 2 particular rheumatoid arthritis, the incidence of disease is even higher. As a result of family and population genetic examinations and immunological diagnostics (in particular proof of auto antibodies) about 10% of the pre-diabetics are currently classified as high-risk candidates who ought to be therapied. However, the therapy strategies suggested up to now (intermittent administration of insulin, temporary immune suppression, NAD application) are not suited to preventing the manifestation of the disease, as the phased sequence of the cell destructions cannot be diagnosed unambiguously and can therefore hardly be therapied. From examinations in animal tests, it is known that the manifestation of IDDM can be prevented with long-term feeding of individual substances connected with IDDM (e.g. insulin, GAD) to pre-diabetic test animals (Nat. Med. (1997) 7:793-796; Diabetologica (1997) 40:902-909). These substances must be absorbed highly cleaned or as gene-manipulated organisms (GMO) in a certain phase of processing. Therefore, the task of the invention was to find substances and to pack them with suitable methods in such a way that they are protected against the decomposing effect of the digestion enzymes. In this way, it is to be possible to use these materials for prevention of auto-immune diseases in small amounts, without gene-manipulation processing and/or time consuming cleaning, in particular as component parts of nutrition. Unlike the predominant working hypotheses, the invention presupposes that the selective reduction of external stimuli is of primary importance for the outbreak of auto-immune diseases. All mammals, including man, have, in the course of their phylogenetic development, developed mechanisms preventing an effect of the absorbed nutrients as an antigenic stimulus, with the result that the nutrition acts as a source of energy and 3 not as a potential antigenic strain. Mammals are immunologically tolerant towards the components of nutrition which maintain this tolerance for an entire life as a result of their intermittent administration. With long-lasting drastic alterations of the nutrition habits, there is the possibility of a deficient or faulty supply of antigens, with the result that a partial or total intolerance towards the nutrition can successively develop. It was established that nutrition habits have distinctly changed in the past 50 years, primarily caused by the increase in affluence, that "lower-quality food" (brain, pancreas, gristle, offal) has mainly disappeared from the nutrition programme. According to the invention, it has been found that undigested and/or partially digested proteins of food are of decisive importance for the induction and maintenance of immuno tolerance of the body towards the nutrients and that the supply of essential mixed proteins, which have mainly disappeared from the human nutrition programme in the past five decades, in the form of capsules, preferably in the form of micro-capsules, in particular as a component part of nutrition, is outstandingly suited to maintaining the condition of immuno-tolerance in mammal organisms. As the effectivity of the applied antigens does not depend on the species, no kinds of problems are to be expected of provision of antigens in human application. Components of nutrition which can be important for maintaining a necessary immuno-tolerance for the prevention of auto-immune diseases can be encapsulated in a dry form or as a solution using methods which are already known per se. The capsules, preferably micro-capsules, with the mixed antigens contained therein, are added to customary foodstuffs such as milk, meat, grain, delicatessen and/or juice products, 4 preferably as nutrient additives, in such a way that the components can be administered in a taste and smell-neutral way. They are added to various dairy products and/or grain products by the manufacturers of foodstuffs, in order to ensure life long and continuous consumption and to enable the maintenance of nutrition tolerance. Encapsulating the added antigens not only results in taste and smell neutrality, but also permits purposeful application of a defined dose of the mixed proteins to be applied into the small intestine, which is of decisive importance for foodstuff tolerance. The foodstuffs manufactured in this way cause a condition of immune tolerance against the antigen mixtures administered by continuous and life-long consumption, thus helping to prevent the creation of an auto-immune disease. Daily consumption of foods encapsulated in this way has been proven to reduce the frequency of the risk of contracting diabetes. Further, the invention contains the benefit that effectivity can also be expected even without the diagnostics of acute immunity thrusts thanks to the intermittent, but life-long continuous supply of the enriched antigens. Purposeful application of the nutrient mixed proteins into the small intestine via preferred alginate-modified micro-capsules makes the proteolytic digestion of the antigens more difficult, with the result that lower doses are sufficient, the place of application corresponding to the place of effect. The same effect occurs if the mixed antigen is included in medication transport systems for oral administration with per se customary pharmaceutical carrier materials.

5 As no similar product has been available on the market up to now, the benefits of the invention can exclusively be deduced in comparison with results from examinations in animal tests. To sum up, it is established: The invention is concerned with the use of taste-neutral capsules, in which one or more antigen substances are enclosed in order to maintain the condition of an immuno-tolerance in mammal organisms, for prophylactics and/or treatment of auto immune diseases such as insulin-dependent diabetes (IDDM), multiple sclerosis and/or rheumatoid arthritis, with essentially customary polysaccharides, polyester and polyamides being used alone or in combination as the covering material of the capsules. Preferably, oligo and/or polysaccharides which are indigestible per se in the digestive tract, e.g. algin acid, polymers of algin acid, alginates, pectins and/or xanthane, if need be together with a physiologically tolerable metal salt, e.g. a calcium salt, are used as the covering material, additionally containing digestible components in the wall of the capsule in a ratio of 30 % up to 80 %, preferably mono, oligo and/or polysaccharides, (poly)hydroxy-carbonic acids, fatty acids as well as their salts and derivatives and also amino acids, their salts and their derivatives. Antigenic substances to be encapsulated are preferably organs, tissue, cells or cell contents of animal or vegetable organisms in a treated or untreated form, the human equivalents of which can be damaged or destroyed by an auto-immune reaction, particularly preferably so-called lower-quality food such as brain, pancreas, gristle mass and/or offal. In a preferred embodiment of the invention, pig's pancreas or pig's pancreas islands encapsulated in alginate are used as prophylaxis and/or treatment of insulin-dependent diabetes, starch being added to the alginate if need be.

6 In this, the capsules are added to a foodstuff, preferably to meat, dairy, grain, delicatessen and/or juice products during or after application for use in maintenance of the condition of immuno-tolerance to an arbitrary substance, without having a lasting influence on the sensoric properties of the final product. The invention also relates to taste-neutral capsules, comprising a per se customary covering material, in which one or more antigenic substances, preferably in form of mixed proteins, are encapsulated, for prophylactics and/or treatment of auto-immune diseases, preferably of IDDM, multiple sclerosis and/or rheumatoid arthritis, with the antigenic substances being essential mixed proteins of all naturally occurring antigens or a part thereof, as they occur in so-called lower quality nutrition, the capsules preferably having a size of 0.2 pm to 500 pm, with micro-capsules preferably 0.5 pm to 20 pm. Example of embodiment The strategy according to the invention was checked in animal tests with the example of insulin-dependent diabetes (IDDM). With examinations on BB rats and NOD mice, animals which develop an IDDM, the effectivity of the "designer food" was proven. The decisive benefit of the procedure according to the invention is in the use of all naturally occurring antigens (application as an enriched mixed antigen), as on the one hand, proof of auto-antibodies (and thus a partial intolerance) against >15 proteins in IDDM clearly relativised the importance of an individual protein, with the result that the singular protein application distinctly limited the preventive efficiency. With an incidence of 0.03 %, 250,000 children and juveniles become ill with IDDM every year in the USA, the EU and in Japan. On the basis of the substantiated assumption that indications of an incipient auto-immune disease can be 7 diagnosed about 5-7 years before manifestation, the target group ought to entail 1.5 million candidates, which extends by 250,000 "pre-diabetics" every year.

Claims

1. Use of taste-neutral capsules, in which one or more antigens are enclosed, for maintenance of the condition of an immuno tolerance in mammal organisms, for prophylactics and/or treatment of auto-immune diseases.

2. Use according to claim 1, wherein per se customary polysaccharides, polyester and polyamides alone or in combination are used as the covering material of the capsules.

3. Use according to claim 1 or 2, wherein oligo and/or polysaccharides which are per se indigestible in the digestive tract, e.g. algin acid, polymers of algin acid, alginates, pectins and/or xanthane, together with a physiologically tolerable metal salt if need be, e.g. a calcium salt, are used as the covering material, additionally containing digestible components in the wall of the capsule in a ratio of 30 % up to 80 %, preferably mono, oligo and/or polysaccharides, (poly)hydroxy-carbonic acids, fatty acids as well as their salts and derivatives and also amino acids, their salts and their derivatives.

4. Use according to claims 1 to 3, wherein the antigenic substances to be encapsulated are organs, tissue, cells or cell contents of animal or vegetable organisms in a treated or untreated form, the human equivalents of which can be damaged or destroyed by an auto-immune reaction.

S. Use according to claim 4, wherein brain, pancreas, gristle mass and/or offal are used. 9

6. Use according to one of the claims 1 to 5, wherein pig's pancreas or pig's pancreas islands encapsulated in alginate are used as prophylactics and/or treatment of insulin dependent diabetes (IDDM).

7. Use according to claim 6, wherein starch is mixed in with the alginate.

8. Use according to one of the claims 1 to 7, wherein the capsules are added to an arbitrary substance, preferably to a foodstuff, preferably to meat, dairy, grain, delicatessen and/or juice products during or after production for maintenance of the condition of immuno-tolerance, without having a lasting influence on the sensoric properties of the final product.

9. Use according to one of the claims 1 to 7, wherein the capsules are used as prophylactics and/or treatment of insulin-dependent diabetes (IDDM), multiple sclerosis and/or rheumatoid arthritis.

10. Taste-neutral capsules, entailing a per se customary covering material, in which one or more antigenic substances, preferably in form of mixed proteins, are encapsulated, for prophylactics and/or treatment of auto-immune diseases, preferably of insulin-dependent diabetes (IDDM), multiple sclerosis and/or rheumatoid arthritis.

11. Taste-neutral capsules according to claim 10, wherein the antigenic substances are essential mixed proteins of all naturally occurring antigens or a part thereof, as they occur in so-called lower-quality nutrition. 10

12. Taste-neutral capsules according to claim 10 and 11, wherein the antigenic substances come from brain, pancreas, gristle mass and/or offal.

13. Taste-neutral capsules according to claims 10 to 12, wherein they have a size of 0.2 pm to 500 pm.

14. Taste-neutral capsules according to claim 13, wherein they have a size of 0.5 pm to 20 pm as micro-capsules.