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Title:  Acceleration of the rate of digestion of a protein

United States Patent:  6,544,515

Issued:  April 8, 2003

Inventors:  Dangin; Martial (Clermont-Ferrand, FR); Garcia-Rodenas; Clara Lucia (Mollie-Margot, CH); Beaufrere; Bernard (Chamalieres, FR); Ballevre; Olivier (Lausanne, CH)

Assignee:  Nestec S.A. (Vevey, CH)

Appl. No.:  588650

Filed:  June 7, 2000

Abstract

The invention thus relates to a method for accelerating the rate of digestion of a protein matter, in which a protein matter is treated with transglutaminase, and it is mixed with anionic polysaccharides. The invention also relates to the use of the rapidly digested protein matter for preparing a food or pharmaceutical composition intended for oral administration to a mammal, to induce a postprandial peak of plasmatic increase in amino acids. This composition is intended for modulating the postprandial protein gain, limiting the problems linked to gastrointestinal motility disorders, limiting the postprandial sensations of nausea in pregnant women, and/or limiting the postprandial risks of regurgitation and/or gastro-esophageal reflux. Finally, a subject of the invention is also a food or pharmaceutical composition comprising anionic polysaccharides and a protein matter treated with transglutaminase.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Contrary to all expectations, the rate of digestion of a protein can be accelerated without previously carrying out its hydrolysis. Similarly, despite past convictions, proteins which are treated with transglutaminase and/or proteins to which anionic fibers are attached have an accelerated rate of digestion. WO 97/05785 (Milupa GmbH) claimed, without demonstrating it, that treating proteins, in particular milk casein, with transglutaminase made it possible to slow their rate of digestion. Similarly, as dietary fibers increase the viscosity of the gastrointestinal content, it was estimated that the time for digestion of all the nutrients present in a meal containing these fibers had, therefore, to be increased (see U.S. Pat. No. 5,126,332).

Finally, the treatments according to the invention, which aim to accelerate the rate of digestion of proteins, did not take place to the detriment of the digestibility of the proteins. The proteins thus treated do not therefore substantially induce an increase in the ratio calculated between the amount of protein ingested orally and the amount of protein absorbed by the body (as an example, see Vaughan et al., Am. J. Olin. Nutrition, 30, 1709-1712, 1977).

In the context of the present invention, "substantially" means within 10%, preferably within 5%, more preferably within 2%.

In the context of the present invention, the expression "plasmatic postprandial peak of amino acids" corresponds to a rapid and noticeable increase in the plasmatic level of amino acids after a meal, followed by a decrease which is virtually as rapid (see FIG. 3).

To implement the present method, a protein matter is used, i.e. all kinds of matter comprising proteins, whether they are of animal, plant or microbial origin, in particular proteins from milk, oilseeds, legumes, egg yolk, or brewer's yeast, for example.

Milk is intended firstly to refer to a milk of animal origin, such as the milk of a cow, goat, sheep, buffalo, zebra, horse, ass, camel, and the like. The term milk also applies to what is commonly called a vegetable milk, i.e. an extract of treated or untreated vegetable matters, such as legumes (soybean, chickpea, lentil, and the like) or oilseeds (rapeseed, soybean, sesame, cotton, and the like), said extract containing proteins in solution or in colloidal suspension, which can coagulate in acid medium. Finally, the term "milk" also refers to mixtures of animal milks and of vegetable milks.

Protein matters with a high nutritive value, according to the recommended rations, such as casein and proteins from egg, from soybean, from pea, from bean, from lentils, from chickpea, from lupin, from carob, from rapeseed or originating from other sources recognized for their nutritive values are particularly indicated in the context of the present invention (FAO/WHO, Protein Quality Evaluation, No. 51, Rome 1991). These proteins can contain a balanced and high content of each of the amino acids which are essential for the body, such as lysine, tryptophan, leucine, isoleucine, valine, phenylalanine, methionine and threonine, for example.

Preferably, the untreated protein matter comprises slowly digested proteins, i.e., proteins which, when ingested by rats weighing 140 to 200 g, can lead to a disappearance of half the ingested nitrogen present in the digestive tract in more than 80 minutes. Proteins which coagulate in the stomach, such as casein, are most frequently slowly digested proteins. Specifically, it is known that the rate of digestion of food proteins is controlled by the stomach, and more specifically by gastric emptying (Gaudichon et al., American Institute of Nutrition, Milk and Yoghurt Digestion 1970-1977, 1994). The coagulum formed in the stomach in this way has trouble leaving, which delays the digestion of the protein.

To implement the present method, this protein matter is then treated with transglutaminase to catalyze polymerization, deamidation, and amine-incorporation reactions (Nielsen, Food biotechnol., 9, 119-156, 1995). The treatment conditions can vary according to the requirements of the present invention. As a general rule, the proteins are suspended in an aqueous medium in a proportion of 1 to 30% by weight, transglutaminase is added in a proportion of 100 to 100,000 units/L, the suspension is subjected to optimal conditions for hydrolysis (pH 7, 5000 units/L), and the enzyme is inactivated by heat and/or by hydrostatic pressure of 300 to 1100 MPa (see EP 686352 and EP 748592 of S.P.N.).

Anionic polysaccharides, in particular chosen from alginates, xanthan, gum arabic, pectins, kappa-carrageenans, iota-carrageenans, lambda-carrageenans, carboxymethylcellulose, sulfated dextrans and/or gellan gum, are then added to the protein matter, before or after treatment with the transglutaminase. The treatment conditions can vary according to the requirements of the present invention. As a general rule, between 0.05 and 30% by w/v of anionic polysaccharides are added.

The conditions for treating the protein matter should preferably be chosen so as to reach a level of acceleration of the rate of digestion of the protein matter such that, when the treated protein matter is administered orally to rats weighing 140 to 200 g, it leads to a disappearance of half the ingested nitrogen present in the digestive tract in less than 70 minutes, for example.

The protein matter thus treated can be used advantageously for preparing a food or pharmaceutical composition intended for oral administration to a mammal, to induce a plasmatic postprandial peak of amino acids, and, as a result, to accomplish one or more of the following: to modulate the postprandial protein gain; to limit the problems linked to gastrointestinal motility disorders; to limit the postprandial sensations of nausea in pregnant women; and/or to limit the postprandial risks of regurgitation and/or gastro-esophageal reflux.

The present use is not however limited to a protein matter treated according to the invention. Specifically, other treatments can also induce an acceleration of the rate of digestion of a protein matter. The present use thus also aims to use any protein matters which have been pretreated so as to transform the slowly digested proteins that it contained into rapidly digested proteins which have at least substantially conserved the same initial molecular weight.

For this, one of the abovementioned protein matters, which has however been treated with transglutaminase, such as those described in WO 97/05785 (Milupa GmbH) can be used, for example. In this case, the molecular weight of the proteins thus treated increases as a result of the polymerization of the proteins.

It is also possible to use only mixtures of proteins and of anionic fibers, such as those described in U.S. Pat. No. 5,126,332, in particular making use of the above-mentioned polysaccharides, for example. In this case, the molecular weight of the proteins thus treated remains identical, but their physicochemical properties are modified as a result of the interaction with the polysaccharides.

Preferably, to implement the present methods, a protein matter which initially contained slowly digested proteins is used, i.e., proteins which, when ingested by rats weighing 140 to 200 g, lead to a disappearance of half the ingested nitrogen present in the digestive tract, in more than 80 minutes.

Protein matters which have a high nutritive value are also particularly indicated. These matters can be exploited in people with a physiological requirement for rapidly digested proteins, such as patients who are in a postoperative or post-traumatic period, children or sportspersons who have just undergone effort, or in people who have a physiological aversion to consuming slowly digested proteins, such as elderly people, people suffering from anorexia, or pregnant women subject to nausea.

The food or pharmaceutical compositions which comprise these accelerated-digestion protein matters are preferably used in the context of diets, or even of therapeutic treatments, for preventing or treating problems linked to specific pathological or physiological states. The conditions governing these diets depend in fact on the categories of people concerned. As a general rule, it will be considered that the composition comprises an amount of protein matter which is sufficient and effective in inducing a postprandial plasmatic peak of amino acids.

More particularly, these compositions are aimed at athletes who are looking to increase their body mass, and more specifically their muscle mass. These compositions can thus comprise a source of proteins which represents 15% to 100% of the total energy. This source can consist essentially of at least one of the treated protein matters described above. Preferably, these compositions comprise treated casein, this casein comprising about 22% valine, leucine and isoleucine, the amino acids being used in the muscle as energetic substrates (Kasperek et al., Am. J. Physiol., 252, E33-37, 1987), and allowing carbohydrate stores to be saved (Blomstrand et al., Nutrition., 12, 485-490, 1996).

Children who exercise physically also have the same physiological requirements as an athlete, particularly after an intense effort. The food compositions for children are preferably formulated to be particularly revitalizing. For this, they comprise, in addition to the source of proteins, a source of carbohydrates which can be rapidly assimilated, lipids, as well as mineral salts and vitamins.

Finally, patients who are in a postoperative or posttraumatic period also have considerable physiological requirements for amino acids. The food compositions are preferably formulated to also be revitalizing. For this, they also comprise, in addition to the source of proteins, a source of carbohydrates which can be rapidly assimilated, lipids, as well as mineral salts and vitamins.

Gastrointestinal motility disorders are often associated with ageing and with pathological states such as anorexia, diabetes, the presence of a gastric carcinoma, neurological disorders (e.g., Parkinson's disease), drug dependency, alcoholism, and the like. The time required for gastric emptying and digestion in these people is abnormally high, which leads to symptoms of anorexia, nausea, and vomiting. These people can thus also have a sensation of satiety which is too strong and protracted after a meal, such that they have difficulties in eating regularly and sufficiently. A composition comprising proteins of high nutritive value, which are rapidly evacuated from the stomach and which are rapidly digested, participates in the elimination of these problems. This composition can thus comprise a source of proteins which represents 10% to 30% of the total energy. This source of proteins can essentially consist of at least one of the treated protein matters described above.

During pregnancy, because of the increase in body mass due to the conception (foetus, placenta) and the hypertrophy of various maternal tissues (uterus, breasts, extracellular fluids), the energy and protein requirements are greater. Many pregnant women suffer from temporary nausea, however, and this hinders them from maintaining a balanced diet. A composition comprising proteins of high nutritive value, which are rapidly evacuated from the stomach and which are rapidly digested, participates in the reduction or elimination of these problems. This composition can thus comprise a source of proteins which represents 10% to 30% of the total energy. This source of proteins can essentially consist of at least one of the treated protein matters described above.

Problems of gastro-esophageal reflux are often observed in pregnant women, newborn babies or premature babies, in particular after ingestion of milk. Current treatments consist in thickening foods and/or in accelerating gastric emptying and in increasing the tonus of the gastro-esophageal sphincter by means of medicaments. The compositions according to the invention are particularly suitable for preventing, or even treating, these problems. These compositions can thus comprise a source of proteins which represents 10% to 40% of the total energy. This source of proteins can essentially consist of at least one of the treated protein matters described above.

More particularly, the compositions comprising anionic polysaccharides have a three-fold advantage for treating problems of reflux. Firstly, the protein matters have a viscosity which limits problems of reflux. Secondly, these protein matters are rapidly removed from the stomach, which also limits problems of reflux. Thirdly, these protein matters are very easily digested.

Finally, newborn babies or patients fed by the enteral route also have problems of regurgitation, which can lead to obstruction of the respiratory pathway. The enteral compositions use complex mixtures of micro- and macro-nutriments in order to improve the nutritional state of the patients. To date, three sources of amino acids have generally been used for these patients, i.e. intact proteins, hydrolyzed proteins (peptides) and amino acids. Amino acids and peptides have an unpleasant taste, and cause an increase in gastrointestinal osmolarity, this parameter leading to the appearance of diarrhea. In addition, the nutritive value of free amino acids is not comparable to that of intact proteins. For intact proteins, most of the enteral compositions use casein. Unfortunately, it coagulates in the stomach and gastric emptying is thus protracted. The present invention aims to use a composition with a good taste, comprising nonhydrolyzed protein matters which are digested very rapidly. This composition can thus comprise a source of proteins which represents 15% to 25% of the total energy. This source of proteins can essentially consist described above.

The food or pharmaceutical compositions comprise, preferably, a source of carbohydrates which provides 50 to 70% of the total energy. Carbohydrates, in particular after a physical effort, after a postoperative trauma, during pregnancy and in newborn babies, are important nutrients for restoring sugar stores, and avoiding hypoglycemia. All the carbohydrates can be used, in particular maltodextrins, saccharose, lactose and glucose.

The food or pharmaceutical compositions can comprise a source of lipids which provides 15 to 35% of the total energy. Vegetable oils are recommended, in particular those originating from soybean, oil palm, coconut palm, sunflower, etc. Minerals, vitamins, salts, emulsifiers or flavor-enhancing compounds can also be added to the compositions, according to the desired requirements.

The food or pharmaceutical compositions can be prepared in all kinds of ways, the manufacturing steps generally including a dispersion of the ingredients in water, and a pasteurization. The compositions can be prepared in the form of drinks or of liquid concentrates, or in the form of a powder which can be reconstituted in water, etc.

Claim 1 of 20 Claims

What is claimed is:

1. A method for accelerating the rate of digestion of milk protein matter, which comprises treating milk protein matter with transglutaminase under conditions sufficient to catalyze polymerization, deamidation, or amine-incorporation reactions in the milk protein matter to obtain treated milk proteins, optionally followed by the mixing of the treated milk proteins with one or more anionic polysaccharides to form a mixture, wherein the treated milk proteins have an accelerated rate of digestion compared to the untreated milk protein matter.

 


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