Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2002-07-16
2004-05-04
Wilson, James O. (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C536S004400, C536S051000, C536S123100
Reexamination Certificate
active
06730661
ABSTRACT:
The present invention relates to nutritional compositions which contain a specific class of non-digestible dextrans, hydrolysed (galacto)mannans and/or hydrolysed (gluco)mannans. These compositions reduce the uptake of high molecular weight substances, allergens and microorganisms through the intestinal wall. In particular, the present invention relates to reduction of the free transport of such substances through the tight junctions (TJ) of the intestines, without the transport of low molecular weight substances, such as nutrients, via the intestinal epithelium being impeded. The compositions can be used to prevent the increased permeability of the intestinal wall, resulting from various causes, and the penetration of toxins, antigens and pathogenic microorganisms present in the lumen which is caused as a result.
The structure and function of tight junctions is described, inter alia, in Ann. Rev. Physiol. 60, 121-160 (1998) and in Ballard T. S. et al., Annu.Rev.Nutr., 1995, 15:35-55. Tight junctions do not form a rigid barrier but play an important role in the diffusion through the intestinal epithelium from lumen to bloodstream and vice versa.
The permeability of the tight junctions is highly regulated and can be disturbed by illness and certain toxins in the lumen. Regulation takes place from the nervous system, the hormonal system and the immune system. When the tight junctions open, substances which have a high molecular weight, allergens and even microorganisms will pass through the tight junctions. The translocation of substances having a high molecular weight can under certain circumstances give rise to sensitisation of the immune system and result in allergic reactions on subsequent exposure. Translocation of pathogenic microorganisms imposes greater strain on the immune system and can make persons and animals ill, inter alia in periods of lowered resistance. The same applies, for example, in the case of bacterial toxins which have been able to pass through the epithelial layer and have been able to reach the bloodstream.
The invention now relates to the use of one or more non-digestible polysaccharides selected from the group consisting of dextrans having a molecular weight of 8 kD to 40,000 kD, hydrolysed (gluco)mannans having a molecular weight of 0.5 kD to 1,000 kD and hydrolysed (galacto)mannans having a molecular weight of 0.5 kD to 1,000 kD to reduce the uptake of high molecular weight substances, allergens and microorganisms through the intestinal wall, with the proviso that the rise in the viscosity of the nutritional composition caused by the polysaccharides is less than 20 mPa.s.
More particularly, the invention relates to the use of the abovementioned compositions to reduce transport of high molecular weight substances, allergens and microorganisms through the tight junctions in the intestines.
In addition to reducing the transport of harmful substances and microorganisms to a significant extent, a significant advantage of the present invention is that the normal transport of useful substances (nutrients) such as glucose, amino acids, dipeptides or trace elements is virtually maintained.
According to the invention non-digestible polysaccharides are understood to be polysaccharides which are not, or are barely, digested or converted by the human digestive enzymes under the conditions prevailing in the body. It should be pointed out that some of the non-digestible polysaccharides can be fermented by the microorganisms present in the intestines (colon, caecum and part of the ileum). Without wishing to be tied to any theory, it is, however, expected that the effect of the polysaccharides on the paracellular transport does not take place via the fermentation products.
The degree to which the polysaccharides are digested can be established using the method as described in Minekus, M., Ph.D. Thesis, University of Utrecht, 1998, Development and validation of a dynamic model of the gastrointestinal tract, Section 2. The polysaccharides according to the invention are less than 50% digestible and preferably less than 30% digestible.
Dextrans according to the invention are understood to be dextrans obtained via a (bio)synthetic route or naturally occurring dextrans. The molecular weight of such dextrans can be regulated by partial acid or enzymatic hydrolysis of the molecule followed by repeated fractionation and precipitation with alcohol or ultrafiltration. These methods, which are known per se to those skilled in the art, must be carried out in such a way that the molecular weight of the dextrans falls within the cited range of 8 kD to 40,000 kD.
Dextrans having a molecular weight of 20 kD to 2,000 kD are preferably used.
The term (gluco)mannans is used to refer both to the mannans and the glucomannans. The same applies in the case of the (galacto)mannans. Examples of galactomannans are guar gum, locust bean gum and tara gum. These (galacto)mannans and (gluco)mannans are used in the hydrolysed form. The molecular weights are between 0.5 kD and 1,000 kD.
Mixtures of dextrans, (galacto)mannans and (gluco)mannans can also be used.
The hydrolysed (galacto)mannans or (gluco)mannans according to the invention can be obtained by partial, but extensive, hydrolysis, for example with the aid of enzymes suitable for this purpose, by means of which substantial quantities of oligosaccharides having a chain length of 3 to 5,600, preferably of 4 to 1,000, are produced.
The polysaccharides are preferably present in the preparation in an amount such that the concentration of these polysaccharides in the intestines is 0.1 to 20 g/l, preferably 0.5 to 10 g/l and preferentially 1 to 6 g/l. The minimum quantity of the active ingredient is determined in that a significant decrease in the transport through the tight junctions is detected.
It is not necessary for the polysaccharides to be administered at that location where the paracellular transport is disturbed. The presence of the active component at a location somewhere in the intestines between the stomach and the affected location is sufficient.
Some of the polysaccharides used according to the invention have a viscosity-increasing action which could prevent the absorption of nutritional components. The preparation must have a composition such that the normal transcellular transport is not impeded.
More particularly, the nutritional composition according to the invention has a viscosity of less than 100 mPa.s, preferably less than 40, but even more preferentially less than 30 mPa.s. For the present invention it is important in particular that the polysaccharides, independently of the other constituents of the composition, have only a low viscosity-increasing effect. The viscosity-increasing effect of the active polysaccharides in the composition must be less than 20 and preferably less than 10 mPa.s and can be, for example, 3 mPa.s. Thus, the major proportion of the viscosity of the product is caused by components other than the polysaccharides in the product.
The viscosity is determined by means of a Carri-med at a shear rate of 100 per second and at 20° C.
In the case of dry products the viscosity limits described above apply after reconstitution of the product.
In general, therefore, the type of polysaccharide (molecular weight) and the concentration thereof will be so chosen that an optimum combination of effectiveness and viscosity is obtained. Not only molecule size, but also degree of branching and degree of loading determine action, viscosity and/or fermentation behaviour.
The polysaccharides according to the invention prevent the free transport of high molecular weight substances, allergens and microorganisms through the tight junctions of the intestinal wall. In this context high molecular weight substances are understood to be the substances which under normal conditions are not able to pass through the tight junctions, or are able to do so only in minor amounts, and which can be assumed to have a toxic or allergenic action. These substances will in general have a molecular size of above 4,000 Dalton. Antigens, substance
Bijlsma Pieter Brandt
Groot Jacques Alphons
Kiliaan Amanda Johanne
Timmermans Johannes Wilhelmus
Van Der Meulen Jan
Krishnan Ganapathy
N. V. Nutricia
Wilson James O.
Young & Thompson
LandOfFree
Nutritional composition which contain non-digestible... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Nutritional composition which contain non-digestible..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nutritional composition which contain non-digestible... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3211829