WO2004056375A1 - Agent for decreasing appetite and for producing a satiation effect, for reducing weight and for lowering the cholesterol level - Google Patents

Abstract

The invention relates to an agent for producing a satiation effect, for reducing weight and for lowering the cholesterol level, containing low-esterified polysaccharides and at least one other compound, which differs from these polysaccharides and which is capable of swelling.

Description

 Means for producing appetite reduction and a satiety effect, for weight loss and for lowering the

cholesterol

The present invention relates to a means for producing a satiety effect, for reducing weight and for regulating the cholesterol balance.

Numerous attempts have been made to reduce excess fat accumulations in the human body by medication or to prevent their formation. There are e.g. So-called appetite suppressants, which try to suggest to the body an aversion to eating in a biochemical way. Some of these remedies have considerable harmful side effects.

In addition to the numerous known diet proposals, there are also mechanical and electromechanical means with which targeted fat loss or muscle building is to take place. However, the effect of such funds is very doubtful.

From DE 4025912 a means for oral ingestion is known which consists of a container which is detachable in the stomach and releases the contents. This is filled with a substance that increases its volume in the stomach after its release, thereby suggesting a feeling of satiety in the body. The disadvantage of this saturant is that there is a risk of intestinal obstructions.

Furthermore, from DE 199 42 417 sponge-like preparations with stably cross-linked cross-links are known which increase their volume in the stomach and thus produce a feeling of satiety. However, that requires Production of these preparations additional process steps for the introduction of stable cross-links.

Due to the constantly increasing health awareness, however, a further improvement of means for producing a satiety effect is of high medical and economic relevance.

The object of the present invention is to provide an improved agent for oral administration which has a longer stomach residence time than known agents of its kind and thus leads to a more effective satiety effect. It should also be suitable for weight loss while regulating cholesterol levels, since obesity is usually associated with an elevated cholesterol level. In addition, simple manufacture from inexpensive raw materials that do not pose any health risks is desirable.

The present object is achieved by a means for producing a saturation effect, for reducing weight and for lowering cholesterol, containing low-esterified polysaccharides and at least one further compound which is different from this and which is swellable, with the exception of aluminum salts of anionic polymers.

Low-esterified pectins, xanthan, tragacanth, chondroite sulfate are preferably used as the low-esterified polysaccharides.

With regard to the low-esterified polymers, the use of low-esterified pectins is also particularly preferred according to the invention. Pectins consist of chains of α-1,4-glycosidically linked galacturonic acid units, the acid groups of which are 20-80% esterified with methanol. A distinction is made between highly esterified (> 50%) and low esterified (<50%) pectins. The molar mass varies between 10-500 kDa. Pectins are obtained by acidic extraction using methods known per se according to the prior art from the inner portions of citrus fruit peel, fruit pulp or sugar beet pulp. The resulting pectins (apple pectin, citrus pectin) are therefore purely vegetable and are highly biocompatible. You can form gels under water absorption.

Here too, the use of pectin gels in the presence of divalent cations such as calcium or barium is known. Because of its toxicity, the latter is not suitable for use in biomedicine. In addition to calcium chloride, calcium gluconate also provides suitable divalent cations. The use of magnesium salts or a mixture of different physiologically harmless divalent cations is also conceivable.

The use of pectins according to the invention is advantageously characterized in that they have cholesterol-lowering properties. This property is advantageous in the sense of the present invention, since obesity is generally associated with an elevated cholesterol level.

In addition to the low-esterified polysaccharides described, the agent according to the invention contains at least one further compound which is capable of swelling. For this purpose, for example, inorganic substances such as MgCl ₂ , CaSO ₂ , Na ₂ CO ₃ , CaCO ₃ , polysilicic acids and clay minerals (such as montmorillonites, zeolites, silicas) or organic substances such as mono- and / or disaccharides (mannose, glucose, sucrose, sorbitol) , Lactose, tartaric acid or urea can be used.

In one embodiment of the present invention, organic polymers are used, preferably those which act as polyelectrolytes. Organic polymers can be natural, semi-synthetic or synthetic with regard to their origin or synthesis. Examples of suitable polymers are polyurethanes, polyacrylates,

Poly (met) acrylic acid esters, homo- and copolymers of vinyl acetate, polyvinyl acetate, polyacrylic acid, polyethylene glycol, polyvinyl pyrrolidone, cellulose, ether, diethyl cellulose or cellulose esters, such as cellulose diacetate, cellulose triacetate, cellulose acetate propionate and cellulose acetate, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl cellulose, hydroxypropyl cellulose, hydroxypropyl cellulose (preferably such higher viscosity compounds); Butyrate, low-substituted hydroxypropyl cellulose, carboxymethyl cellulose (with 2 or 3-valent cations), sodium starch glycolate, glycosaminoglycans such as chondroitin sulfate or hyaluronic acid, collagen, albumin, keratin, conchagens, fibroin, elastins, chitin.

Hydrocolloids, particularly preferably based on polysaccharides, are preferably used.

The use of anionic polymers is particularly preferred. These preferably include polysaccharides, especially those containing polyuronic acid

Polysaccharides. Alginic acids, their derivatives and salts (alginates) are particularly preferred. In a preferred variant of the invention, all anionic polymers come in with the exception of the aluminum salts

Consideration. In particular, the aluminum salts of alginic acids are excluded. However, all other uronic acid-containing compounds can also be used according to the invention. The use of cellulose or cellulose derivatives is also preferred according to the invention.

The use of synthetic or semi-synthetic is conceivable

Cellulose derivatives, e.g. Carboxymethyl cellulose or polyacrylates.

Cellulose is understood to mean water-insoluble polysaccharides of the gross composition (CeH-ioOsJn. More specifically, it is an isotactic β-1,4-polyacetal of cellobiose (4-O-β-D-glucopyranosyl-D-glucose). Chemically modified celluloses are generally defined as cellulose derivatives by polymer-analogous reactions. They include both products in which hydroxyl-hydrogen atoms of the anhydroglucose units of cellulose are substituted by organic or inorganic groups exclusively, for example via esterification and / or etherification reactions, as well as those with formal exchange of hydroxyl groups of the natural polymers against functional groups that are not bound via an oxygen atom (eg deoxycelluloses) or via intramolecular elimination of water (anhydrocelluloses, celluloses) or oxidation reactions (aldehyde, keto and carboxycelluloses). Products which cleave the C ₂ , C ₃ carbon bond of the anhydroglucose units (dialdehyde and dicarboxy celluloses) and in which the monomer unit characteristic of the cellulose is no longer intact are also included in the cellulose derivatives. Cellulose derivatives are also accessible via other reactions, for example via crosslinking or graft copolymerization reactions.

The use of cellulose or cellulose derivatives in a mixture with pectins is advantageous according to the invention. Mixtures containing alginic acid or its derivatives are likewise preferred, aluminum salts of alginic acids preferably being excluded and pectins being preferred.

Alginic acid is a linear polyuronic acid consisting of alternating proportions of D-mannuronic acid and L-guluronic acid, which are linked to one another by β-glycosidic bonds, the carboxyl groups not being esterified. One molecule of alginic acid can be composed of about 150-1050 uronic acid units, with the average molecular weight varying in a range of 30-200 kDa. The polysaccharide alginic acid is a component of the cell walls of brown algae. The proportion of alginic acid in the dry mass of algae can make up to 40%. The alginic acid is obtained by alkaline extraction using methods known per se according to the prior art. The resulting powdered alginic acid is therefore purely vegetable and has a high level of biocompatibility. It can absorb 300 times its own weight in water, forming highly viscous solutions. In the presence of polyvalent cations, alginic acid forms so-called gels. The formation of alginate gels in the presence of divalent cations, such as calcium or barium, is described in Shapiro I., et al. (Biomaterials, 1997, 18: 583-90). However, due to its toxicity, the latter is not suitable for use in biomedicine. In addition to calcium chloride, calcium gluconate also provides suitable divalent cations. The use of magnesium salts or a mixture of different physiologically harmless divalent cations is also conceivable.

The agent according to the invention preferably has the described compounds in powder form. That is, the agent can be in the form of an adsorbate, beadlet powder, granulate, pellet, extrudate and / or combinations thereof. Use forms in which the particles are coated are also conceivable.

The agents, which are preferably in powder form according to the invention, can be prepared using methods known per se. This includes, for example, the production of spray formulations. A method and unit that can be used for this are described, for example, in EP 0 074 050 B1. In addition to this type of production, other process variants are also conceivable. These include, for example, spray drying processes or the production of adsorbates in fluidized beds.

To produce a powdery agent according to the invention, for example, a solution of the low-esterified polymers in water can be prepared and e.g. be thickened with the addition of calcium salts. A gel or foam can be obtained by incorporating air and possibly adding surfactants. By freezing and then freeze-drying, a dry gel or dry foam (sponge) is produced from the alginate gel or foam. The other compounds, which must be swellable according to the invention, can be prepared in an analogous manner.

In addition to the addition of inorganic or organic calcium salts, e.g. Calcium chloride or calcium gluconate, it is also conceivable to use magnesium salts and mixtures of different physiologically acceptable divalent or trivalent cations.

The production of granules can be achieved in that carriers and / or spray-dried powders and optionally additives are placed in a mixer and compact granules are produced by adding the active components and / or binders and / or additives. Mixers preferably used in this process are, for example, paddle mixers or ploughshare mixers. The liquid components can be dropped or sprayed on, for example, so that a pasty, sticky phase is formed. The pasty phase is distributed by suitable selection of the speed of the mixing tools and / or high-speed knives and compact granules are formed. Very large chunks are cut by mixing tools and knives and on the other hand fine powders are agglomerated. By adding cladding layers can downstream in the mixer at a lower speed of the mixing tools and stationary knives or in a design-related downstream mixer.

The agent according to the invention can be used in various conventional ways

Dosage forms are produced. For example, in

Form of tablets, capsules, dragees, as granules or powder or other configurations.

The agent according to the invention can also contain further auxiliary substances and / or active substances.

“Auxiliaries” are understood to mean, for example, the following substances, which, however, are not limiting for the present invention: water-insoluble auxiliaries or mixtures thereof, such as lipids, including fatty alcohols, for example cetyl alcohol, stearyl alcohol and cetostearyl alcohol; glycerides, for example glycerol monostearate or mixtures of mono-, Di- and triglycerides of vegetable oils; hydrogenated oils, such as hydrogenated castor oil or hydrogenated cottonseed oil; waxes, e.g. beeswax or carnauba wax; solid hydrocarbons, e.g. paraffin or earth wax; fatty acids, e.g. stearic acid; certain cellulose derivatives, e.g. ethyl cellulose or acetyl cellulose; polymers or copolymers, such as Polyalkylenes, for example polyethylene, polyvinyl compounds, for example polyvinyl chloride or polyvinyl acetate, and also vinyl chloride-vinyl acetate copolymers and copolymers with crotonic acid, or polymers and copolymers of acrylates and methacrylates, for example copolymers of acrylic acid esters and methacrylic acid methyl esters; or surfactants, wi e e.g. Polysorbate 80 or Docusat. “Active ingredients” are to be understood to mean, for example, vitamins, trace elements or medicinal active ingredients. The following substances are listed by way of example, but are not limiting for the present invention:

Examples of appetite suppressants are: amfepramon, fenfluramine, fenproporex, levopropylhexedrine, mazindol, mefenorex, metamfepramon, norephedrine, norpseudoephedrine.

Examples of antivirals are: acyclovir, cidofovir, didanosine, famciclovir, foscarnet, ganciclovir, lamivudine, ritonavir, zalcitabine, zidovudine.

Examples of vitamins are: alfacalcidol, allithiamine, ascorbic acid, biotin, calcifediol, calcitriol, colecalciferol, cyanocobalamin, ergocalciferol, folic acid, hydroxocobalamin, nicotinamide, pantothenic acid, phytomenadione, pyridoxine, retinol, riboflavocinophene, transiolamine, thiolamine.

Under certain circumstances, a delayed release of active ingredient can also take place here.

In addition to the auxiliaries and active substances mentioned, the agent according to the invention can additionally contain fillers, disintegrants, binders and lubricants as well as carriers which have no decisive influence on the release of active substances. Examples include bentonite (aluminum oxide-silicon oxide hydrate), silica, cellulose (usually microcrystalline cellulose) or cellulose derivatives, for example methyl cellulose, sodium carboxymethyl cellulose, sugars such as lactose, starches, for example maize starch or derivatives thereof, for example sodium carboxymethyl starch, starch paste, phosphoric acid salts, for example di - or tricalcium phosphate, gelatin, stearic acid or suitable salts thereof, for example magnesium stearate or calcium stearate, talc, colloidal silicon oxide and similar auxiliaries. The agent according to the invention can be used to produce a satiety effect, to reduce weight and to regulate the cholesterol balance. It is also suitable for the preparation of a composition for producing a satiety effect, for reducing weight and for regulating the cholesterol balance.

Accordingly, the agent can also contain substances that stimulate intestinal activity. In particular, indigestible substances that promote intestinal activity, preferably herbal natural components, come into consideration here. Examples of this are fiber.

Claims

Expectations: 1. Means for producing a saturation effect, for weight reduction and for cholesterol lowering containing low-esterified polysaccharides and at least one other different from them Connection that is swellable. 2. Composition according to claim 1, characterized in that the swellable compound contains anionic polymers. 3. Composition according to one of claims 1 or 2, characterized in that polysaccharides are contained as anionic polymers. 4. Composition according to one of claims 1 to 3, characterized in that it contains polyuronic acid-containing polysaccharides. 5. Composition according to one of claims 1 to 4, characterized in that it contains alginic acid or its derivatives or cellulose or its derivatives or mixtures of the compounds mentioned as polyuronic acid-containing polymers. 6. Composition according to one of claims 1 to 5, characterized in that it contains pectins, xanthan, tragacanth, chondroitin sulfate or mixtures of these compounds as the lower esterified polymers. 7. Composition according to one of claims 1 to 6, characterized in that it additionally contains active ingredients. 8. Composition according to one of claims 1 to 7, characterized in that it contains vitamins, trace elements or medicinal active substances as active substances. 9. Composition according to one of claims 1 to 8, characterized in that it is in the form of a powder. 10. Use of an agent according to any one of claims 1 to 9 for producing a satiety effect, for weight reduction and for regulating the cholesterol balance. 11. Use of an agent according to any one of claims 1 to 9 for the preparation of a composition for producing a Saturation effect, for weight loss and for regulating the cholesterol balance.