JPH02215722A - Method and agent for reducing food fat - Google Patents

Abstract

PURPOSE: To diminish the metabolism and accumulation of food lipid in vivo by introducing non-biodegradable particles having lipid receptor on its surface into the gastrointestinal tracts to absorb and stick the food lipid released from food and excluding the lipid out of the body. CONSTITUTION: Non-biodegradable particles having the particles size that cannot pass through the mucous membrane on the surface of gastrointestinal tracts (>=2μm, particularly >=5μm) and has a lipid receptor for absorbing and binding to food lipid on its surface (bile is suitable) are introduced into the gastrointestinal tracts to absorb and stick the food lipid liberated from the food to the lipid receptor on the particle surface. Then, the particles having lipid stuck to its surface are excreted out of the body together with the body wastes. As non-biodegradable particles, are used, for example, collagen, crosslinked albumen, cellulose and the like.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates generally to novel and useful improvements in methods for reducing dietary fat, and more specifically to methods for reducing dietary fat in the gastrointestinal tract of animals. The present invention relates to a method and a fat-reducing agent for reducing dietary fat, which allows the dietary fat to pass through the gastrointestinal tract and be released from the body via body excretion.

BACKGROUND OF THE INVENTION Weight loss has become a serious problem, especially in developed countries, ie richer countries, where food scarcity is less pronounced. Obesity is not only undesirable from an aesthetic point of view, but also causes various health problems.
It particularly causes and contributes to coronary artery and related problems.

Excessive dietary fat intake and absorption through the bloodstream is one of the main causes of obesity, and it is therefore desirable to regulate dietary fat intake. A variety of dietary treatments have been proposed, and these are moderately effective in reducing fat intake. However, all the woodiness of these diets halve the culinary pleasure associated with food intake, and in most cases result in rather unappealing food combinations. Therefore, many dieters abandon their diet programs and therefore abandon control over fat intake.

It is also known that dietary fat intake increases blood fat concentrations, such as cholesterol and triglycerides. It has also been established that some increase in blood fats is associated with a higher risk of coronary artery problems. Therefore, it is also desirable to reduce the level of fat in the blood by reducing fat intake.

Cholestyramine, commercially available under the trademark Questeran J
amin) resins are used to reduce cholesterol fat levels in the bloodstream. It has been found that there is a high excretion loss of bile acids due to administration of this cholestyramine powder resin. This leads to significant oxidation of cholesterol to bile acids, as well as lower β-ributon protein and consequent reduction in serum cholesterol concentrations. However, there are a number of untoward side effects associated with the administration of Questeran, cholestyramine resin powder. First, this cholestyramine resin has the effect of significantly delaying the absorption of other oral drugs. More importantly, administration of this cholestyramine resin appears to inhibit absorption of fat-soluble vitamins. As a result, no fat-soluble vitamins can be administered during use of this cholestyramine resin. It has also been found that the incidence of tumors observed in rats is significantly higher when cholestyramine is administered. Other side effects worth mentioning are adverse effects during pregnancy, constipation, and abdominal discomfort. Therefore, there are also significant contraindications to the use of cholestyramine in reducing serum cholesterol concentrations.

SUMMARY OF THE INVENTION To date, there have been no proven effective methods and compositions for reducing the absorption of dietary fat by the body without a restrictive dietary regimen. Therefore, what is needed are compositions and/or methods that can reduce the metabolism and accumulation of dietary fat in the body without dietary restrictions.

SUMMARY OF THE INVENTION From a broad perspective, the present invention relates to a method of accumulating and binding dietary fat within the gastrointestinal tract of an animal body to reduce absorption by the body's bloodstream. Here, the terms "animal" and "animal body" are used in a broad sense and are intended to include all species of animals, and in particular domesticated animals. However, the invention is primarily useful for humans.

The method of the invention comprises the step of introducing biodegradable particles having fat receptors on their surface into the gastrointestinal tract of an animal. Fat liberated from food in the animal's stomach attaches to fat receptors on the particles. This usually occurs below the stomach, for example - within the duodenum.

The fat-laden particles then pass through the gastrointestinal tract and are released from the body as body waste, such as feces.

In one important aspect of the invention, the particles should have a sufficiently large particle size so as not to penetrate the superficial mucosa of the gastrointestinal tract. Generally, the particles are at least about 2μ
, and more preferably should have a particle size of at least about 5 microns. Particles that can be used can be employed as non-biodegradable fibers or other materials that are not biodegradable (hereinafter referred to as "non-biodegradable"). For example, collagen functions as an excellent particle in the present invention. This collagen can be made non-biodegradable by crosslinking with a suitable reducing agent, such as glutaraldehyde or other reducing agent.

It is usually desirable to complex bionon-degradable particles, such as collagen, carrying fat receptors with emulsifiers. Fats free from food and many non-biodegradable particles, such as collagen, are generally insoluble in water. Otherwise, water would be the primary carrier of any such particles in the gastrointestinal tract. Thus, the receptor-loaded non-biodegradable particles are usually combined with an emulsifier, such as gum arabic.

In one preferred embodiment of the invention, bile is the preferred fat receptor. Bile is also one of the components produced by the body to store fat in the body, and is therefore a non-biodegradable substance that stores fat and releases the fat from the body through excretion from the body. Acts as an excellent fat receptor on the surface of the particles.

Particles that can be used in the present invention are non-biodegradable and can employ ground collagen as described above.

One preferred particle that has been found to be highly effective in the present invention is non-biodegradable plastic microspheres. Furthermore, it has been found to be effective to form an emulsion of the particles with other substances, such as rubbery substances such as guar gum.

Action: Attach bile or other fat receptors to cross-linked collagen particles, microspheres or other non-biodegradable fibers. In fact, fat is attached to this fat receptor and not to the fibers; moreover, emulsifiers, such as gum arabic, actually bind fat and bile onto the non-biodegradable particles. It acts like a seal. Additionally, the emulsifier functions to accumulate water in the combination.

The present invention also relates to compositions that collect and bind dietary fat liberated from food products in the animal gastrointestinal tract. The composition includes bionon-degradable particles having a particle size of at least about 2 microns and large enough to not penetrate the superficial mucosa of the gastrointestinal tract, the particles having fat receptors thereon as described above. , on which food fat is deposited, and the deposited dietary fat is passed through the gastrointestinal tract and released outside the body as excreta from the body.

EXAMPLES In the present invention, non-biodegradable particles carrying fat receptors are used to absorb dietary fat in the gastrointestinal tract, thereby inhibiting absorption of fat by the body.

According to the methods and compositions of the present invention, the dietary fat completely passes through the gastrointestinal tract and is excreted from the body as waste.

There is good evidence that bile production in the human body is utilized for dietary fat absorption. Unless the dietary fat is insoluble in any polar solvent, such as water, the body emulsifies the fat liberated from the food grains in the stomach and forms a liquid emulsion.

This liquid bile emulsion travels in droplets into the gallbladder blood vessels and is then sent to the liver. The liver produces fatty fluid, which then enters the bloodstream. After all, fat is actually absorbed by the body.

Cholesterol is thought to be the only precursor of bile acids that is most likely and more reliably produced. Thus, during normal digestion, bile acids are secreted from the liver and gallbladder into the intestines as bile. Bile acids emulsify fats and lipid substances present in foods. This facilitates absorption. Most of the secreted bile acids are reabsorbed in the intestines,
It is returned to the liver via the hepatic portal circulation. The enterohepatic cycle is thus completed.

In connection with the present invention, it has been discovered that, given a mechanism that interferes with the absorption of fat in the body, typically within the duodenum, fat generally passes through the gastrointestinal tract and is excreted from the body as waste from the body. Ta. One of the important aspects is that the fat depositing particles must be large enough not to penetrate the superficial mucosa of the leg, and must also be non-biodegradable.

In accordance with the present invention, administration of bionon-degradable particles carrying fat receptors is effective in reducing the production of low-density lipoprotein cholesterol (often referred to as LDL cholesterol) and high-density lipoprotein cholesterol (
It has been found to be effective in promoting the production of higher amounts of HDL (often referred to as HDL). The spherules effectively block absorption of free fatty acid bile complexes by the body.

As a result, less fat is available to the liver for the production of LDL cholesterol. Eventually, the body activates body tissues to produce HDL cholesterol. Thus, in accordance with the present invention, it has been discovered that the methods and compositions of the present invention not only reduce fat mass for weight control, but also reduce the amount of low density cholesteronyl in the body's bloodstream.

The particles used may be non-biodegradable to begin with, for example microspheres as described above. The particles can also be made non-biodegradable, for example by cross-linking. In either case, it is necessary to attach fat receptors to the surface of the particles so that food fat can be adsorbed thereto. A schematic illustration of a fat receptor, such as bile, on the particle with attached fat is more fully shown in FIG.

In this case, the reference numeral 10 represents a particle, for example a collagen particle, which is crosslinked with crosslinks 12 by a crosslinking agent. Fat receptors such as bile are attached to chains of various collagen particles. Additionally, fat actually attaches to bile or other fat receptors as shown.

According to the invention it is also important to use emulsifiers. The emulsifier can be administered separately with the biodegradable particles, or the emulsifier can be mixed with the biodegradable particles and administered as a mixture. This emulsifier is generally effective in encapsulating fat and bile onto non-biodegradable particles. Additionally, as mentioned above, emulsifiers are effective in creating an environment in which the fat is kept in a liquid phase. This will reduce the possibility of constipation, gas formation and other complications that may occur within the lower gastrointestinal tract.

The most preferred form of particles found is fibrous particles such as collagen. Tanned collagen is more preferred; tanned collagen can be cut into sheets and ground into small particles. When provided with suitable fat receptors, the milled particles can absorb 3 to 4 times their weight in dietary fat.

Other non-biodegradable materials that can be used include cross-linked albumin as well as various other non-digestible, plant proteins such as cellulose.

One of the more preferred forms of particles that have been found to be useful in the present invention are non-biodegradable microspheres. The group is exposed or is easily crosslinked to a solid that can be exposed by appropriate treatment. This includes, but is not limited to, latex materials such as polystyrene and styrene divinylbenzene, agarose, polyalkyl cyanoacrylates, albumin, cross-linked albumin, sucrose, starch, cellulose and dextran.

The microspheres are extremely effective because they are retained for a substantial period of time.

Typically, latex microspheres are stored with a colloidal silica coating and the coated spheres forming a 10% solids suspension in water.6 Generally, prior to fat receptor application, the microspheres are purified by vacuum filtration and drying. can.

As mentioned above, it is necessary to apply fat receptors to the surface of the particles. One of the most preferred fat receptors is bile, insofar as bile is known to be highly effective in depositing fat within the body itself. Another receptor that can be used is cholestyramine powder. Generally, any bile salt can be used as a fat acceptor.

Another highly useful fat receptor that can be used in the present invention is colestipol, which is commercially available under the name Colestid.
It is hydrochloride. Colestibol hydrochloride generally exists as a high molecular weight basic anion-exchange copolymer of diethylenetriamine and 1-chloro-2,3-epoxypropane.

Another fat receptor that can be used in the present invention is Lopid, which is usually suitable for oral administration, often under the trade name Lopid.
Gem 74 prozil (geo+fibroxil), commercially available as pid) J. This gemfibrozil consists of 5-(2,5-dimethylphenoxy)-2,2-dimethylphenoxy acid with the empirical formula C15H2203 at -a. A further suitable fat receptor is niacin (N1a
cin). This niacin functions in the body as a hydrogen transport coenzyme, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate.

Several emulsifiers can be used to create an emulsified solution of fat attached to fat receptor particles. The emulsifier produces an intimate mixture between two components that would otherwise be immiscible. As a result, the emulsifier provides a stable emulsion. One of the preferred emulsifiers is gum arabic, a dried gummy extract from the stems and branches of the acacia plant. Generally, this gum arabic consists primarily of the calcium salt of arabic acid, which is hydrolyzed to produce galactose and arabinose acid. Another emulsifier that can be used is guar gum, which is
arem) is commercially available under the trade name J. Other emulsifiers that can be used include sodium algenate, sodium lauryl sulfate, gum arabic, etc.Essentially any emulsifier that is compatible with the body and capable of emulsifying fat and non-biodegradable particles can be used. can.

It is often desirable to tan the non-biodegradable particles used. In fact, non-biodegradable particles are crosslinked by difunctional groups such as glutaraldehyde. However, no tanning operation is required.

The non-biodegradable particles should have a suitable size, usually about 2 microns or more, preferably about 5 microns or more. In this way, the particles will not penetrate the surface mucosa of the intestinal tract, and there is generally no upper limit to the particle size. The only requirement is that the particles be large enough so that they do not pass through the superficial mucosa of the gastrointestinal tract. However, from a practical point of view, there is no clear maximum limit, but typically around 50
Does not exceed μ.

Usually fat receptors are bound to non-biodegradable particles in a water bath. The non-biodegradable particles, such as collagen, are dispersed in water using rather vigorous agitation. Fat receptors are also generally dispersed in water under acidic conditions, for example at a pH of about 2-4, preferably 3, and then a mixture of the two is blended. An emulsifier such as glutaraldehyde is then added to the solution to emulsify it. This solution is then air dried to form a solid composition.

Thus, the present invention provides unique and novel compositions comprising at least bionon-degradable particles or particles rendered bio-non-degradable complexed with fat receptors such as bile.

Example 1 - This example describes the preparation of a composition used to collect and bind dietary fat.

Although bovine Achilles collagen was used to form the non-biodegradable particles or carrier, collagen from any other source can also be used. Approximately 500 B of Achilles collagen was introduced into a chilled Waring blender. Thereafter, 100 mJ2 of distilled water is charged into the blender to sufficiently disperse the collagen in the blender. The pH of the water was adjusted to an acidic pH of approximately 3 by the addition of lactic acid. Blending with water carrier collagen occurs by cycling the blender at 10 second intervals.

A second solution of porcine bile extract was dissolved in 3 mA of distilled water. Approximately 300 mg of porcine bile was used. The pH of the water was adjusted to about 3 acidic. The two solutions were then blended.

A 25% solution of glutaraldehyde was used as a crosslinking agent;
This was added to the mixed solution to give a concentration of 5%. Afterwards, a thorough stirring was performed. The resulting composite constituted a crosslinked collagen fibrous formulation entrapped by bile extract.

Next, this composition is developed on a paraffin film,
Air dried. Recovery is about 70 to about 90 of the initial weight of starting material.
%.

EXAMPLE 2 This Example 2 describes the binding of dietary fat to the fiber-bile composition prepared according to Example 1. The binding of dietary fat to the fiber-bile composition was determined by measuring the activity of bile acids. All unbound bile, ie, bile without bound fats, inherently exhibits bile acid activity. The activity of bile acids is determined by the supplementary oxygen nicotinamide adenine dehydrogenase (NAD).
) with 3-α-hydroxysteroid dehydrogenase (coupled enzyme reaction with 3-α-hydroxysteroid dehydrogenase)
It was measured using the following software.

The standard curve plot for this reaction is a straight line according to Beer's law. When free fatty acids or cholesterol liberated from food products are bound to bile acids, bile acid activity is reduced or eliminated. Therefore, binding of dietary fats can be measured by following inhibition of bile acid activity.

To test the binding of dietary fat to the fiber-bile complex of Example 1, bile acid activity was tested both in the presence and absence of sodium barmate. The fiber-bile complex assembly was incubated with a solution of sodium barmate. Furthermore, sodium palmate was published in the journal Van Harken et al.
of Biological Chemistry (Journal
of Biological Chemistry),
1969.244(9), 2278. This suspension of m1a-biocomplex in sodium barmate was found to be stable in the glycerol-hydrazine reagent.

10mg collagen formula, 0 sodium balmate
．． 5mj2 for approximately 1 hour at 37°C. At the completion of the incubation period, the eluate was removed and tested for bile activity. A bile acid activity control that did not contain sodium balmate was also utilized in conjunction with this evaluation. Bile acid activity without sodium palmate was 454 units and with sodium palmate was 205 units. This resulted in a 54% reduction, which was proportional to the proportion of fat bound to the non-biodegradable particles.

The following examples describe the use of fat binding pills adapted for use in humans.

According to this Example 3, the collagen-bile complex containing an emulsifier prepared according to Example 1 was added to the prepared building block. However, in this case, gum arabic was used as the insoluble carbohydrate complex emulsifier. Equal amounts of the emulsifier and collagen-bile complex were placed in a container, and then formed into a gelatin capsule shape. Starting capsules are 500m each.
g emulsifier and collagen-bile complex.

Husband tm A normal adult male was placed on a mild calorie-restricted diet of 1800 calories/day instead of a normal calorie intake of approximately 2200 calories/day. 1 g of the capsules of Example 4 were ingested with each meal.

This man's weight was measured at the same time in the morning every day, and
A complete blood profile was completed before and at the end of the weekly period. 7 with the regimen described here.
Bond weight loss was achieved (see Figure 2 of the accompanying drawings).

Total serum cholesterol was virtually unchanged. HD
L-cholesterol increased from about 27 to about 85, and LDL-cholesterol decreased proportionately. This man's stool clearly showed an increase in fat content as it floated on water.

Normal adult women were also placed on a diet designed to cause weight loss. This diet provided approximately 1400 calories/day. This calorie was less than the normal consumption of about 2300 calories/day. This program is about 3
When continued for a week, it resulted in a weight loss of 16 pounds.

Her HDL cholesterol level increased from 23 units (value at the beginning of the 3-week period) to 38 units at the end of the period. Additionally, LDL cholesterol decreased from 155 units at the beginning of this 3 week period to 140 units at the end of the period.

EFFECTS OF THE INVENTION The methods and compositions of the present invention have also been found to be effective in improving the ratio of high-density lipoprotein cholesterol to low-density lipoprotein cholesterol. The fat receptor-non-biodegradable particles of the present invention will actually block the absorption of free fatty acid biocomplexes, resulting in the production of low-density lipoprotein cholesterol, which is associated with a higher risk of coronary artery problems. Very little fat is used. As a result, a higher proportion of high-density lipoprotein cholesterol is circulated in the body's bloodstream.

In connection with the present invention, it has also been found that by binding fat to non-biodegradable particles with emulsifiers, only significantly less water is absorbed from the digested food passing through the large intestine. As a result, the methods and compositions of the present invention inherently regulate water absorption by the body and avoid constipation. Thus, the methods and compositions of the present invention are effective in reducing the occurrence of constipation and also in reducing fat absorption by the body.

The method of the invention has many other advantages and other objects that will become more apparent from the above discussion of the embodiments embodying them, which embodiments have already been described in detail. It should be understood that the above detailed description is provided to illustrate the general principles of the invention and is not to be construed in a limiting sense.

[Brief explanation of the drawing]

FIG. 1 schematically shows the relationship between the various components forming part of the compositions of the invention and their functions; FIG. It is a figure which shows a weight loss effect by a graph. 10...Particles, 12...Crosslinking.

Claims (8)

[Claims] (1) A method for reducing dietary fat, which collects, binds, and excretes dietary fat released from food products in the gastrointestinal tract of an animal, comprises the following steps: a) permeates the mucous membrane on the surface of the gastrointestinal tract; Particles with a particle size that is not biodegradable, have fat receptors on their surface to absorb and bind dietary fat, and are not biodegradable (hereinafter referred to as non-biodegradable particles) in the gastrointestinal tract of animals. b) sucking and adhering dietary fat released from food in the gastrointestinal tract to fat receptors on the surface of the particles; c) introducing the fat attached to the non-biodegradable particles into the gastrointestinal tract. The step of passing through a tube and exiting the body along with the body's waste products. 2. The method according to claim 1, further comprising the step of: (2) liberating the fat in the stomach of the animal and attaching the fat to the fat receptors of the non-biodegradable particles in the duodenum. How to reduce dietary fat. (3) The method of claim 1, wherein the non-biodegradable particles have a particle size of at least about 2 microns. (4) A fat-reducing agent that collects and binds fats liberated from food products in the gastrointestinal tract of animals, comprising bionon-degradable particles having a particle size of at least 2μ;
and a fat receptor to which dietary fat is attached on the surface of the non-biodegradable particles, the size of the non-biodegradable particles is at least large enough not to pass through the surface mucosa of the gastrointestinal tract,
A fat-reducing agent characterized in that non-biodegradable particles adhering to fat released from animal food are small enough to pass through the gastrointestinal tract and be released outside the body via animal excreta. (5) Claim 4 characterized in that it contains an emulsifier.
The fat reducing agent described in. (6) The fat reducing agent of claim 4, wherein the non-biodegradable particles have a particle size of at least about 5 microns. (7) The particles include particles that are not generally biodegradable in the gastrointestinal tract of an animal and food particle fat receptors on the surface of the particles, and the particles have dimensions that do not penetrate the surface mucosa of the animal gastrointestinal tract. composition. (8) The composition according to claim 7, wherein the particles are crosslinked.