Note: Descriptions are shown in the official language in which they were submitted.
v
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Utilization of capsules containing one or more antigenic
substances for prevention and/or treatment of autoimmune
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
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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 inv. 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
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of energy and 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,
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- 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.
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As no similar product has been available on the market up to
now, the benefits of the inventj~on 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
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prophylaxis and/or treatment of insulin-dependent diabetes,
starch being added to the alginate if need be.
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 ~,m to 500 um, with micro-capsules preferably 0.5
~.m to 20 ~Cm.
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.
r
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With an incidence of 0.03 0, 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
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.
