EA016545B1 - Use of calcium-peptide composition for preventing and/or treating type ii diabetes - Google Patents

Abstract

The invention relates to the use of a calcium-peptide composition obtained from at least one calcium salt, at least one caseinophosphopeptide (CPP), and/or at least one glycomacropeptide (GMP) for producing an agent for preventing and/or treating type II diabetes. Administering said composition makes it possible to significantly suppress the onset of type II diabetes (antidiabetogenic effect).

Description

(57) The invention relates to the use of a calcium peptide composition comprising at least one calcium salt, at least one casein phosphopeptide (CPP) and at least one glycomacropeptide (GMP), for the manufacture of an agent for the prevention and / or treatment of diabetes mellitus II type. When taking this composition, it is possible to significantly reduce the likelihood of type II diabetes mellitus (antidiabetogenic effect).

The invention relates to the use of a calcium peptide composition for the prevention of diabetic metabolic disorders.

The prevention of such metabolic disorders, which begin in a person in early childhood and may result in the onset of diabetes mellitus, is now one of the most important tasks, since this disease, which can also be caused by malnutrition, is a typical disease of civilization, mainly in Europe and the USA, with an ever-increasing number of cases (in 2010 alone in Europe there will be about 33 million people).

In recent years, calcium has increasingly been the subject of discussion in the scientific literature in relation to weight control in obese people. A variety of mechanisms have been used to explain the causes of this phenomenon. On the one hand, the action of calcium was explained by a hormone-like action (2et1, M.V .; 1. At. Co11. Νυίτ. 21, p. 146-151 (2002)). This principle of operation, among other things, is described in US patent No. 6 384 087 or in European patent EP No. 1343390.

In this case, it is similarly based on the fact that calcium, due to the formation of calcium soap in the intestine, prevents the absorption of fats, which results in a decrease in the absorption of fat in the intestine (Acacia, B.; Bogep / Ep. 1. K .; Toyo, 8. ; Kgod-M1kke18ei, I .; Ak! Gir, A .; 1i1egi. 1. Oekyu 29, p. 292301 (2005)).

Further, in the literature there are still references to the fact that calcium should always be taken with dairy products, if the goal is to reduce body weight. However, there are also works that show that the consumption of dairy products does not necessarily lead to success (OiShet, S. e! A1; Integ. 1. SI. ΝιιΙγ. 81, pp. 751-756 (2005)).

The aforementioned control of body weight by taking calcium is also a subject of discussion in medical circles as part of the discussion of the so-called metabolic syndrome. An important role, among other things, is given to the regulation of blood pressure. One of the consequences of the metabolic syndrome is type II diabetes mellitus. Different groups of researchers have been studying the question of whether regular calcium intake can lower high blood pressure. There are a number of studies (MsSaggoi, Ό. A.; Weikkeg, M. E .; 1. Ateg. Co11. ΝιιΙγ. 18, pp. 398-405 (1999); Vokyssk, V. M. e! A1; AgsN Eatt. Mei., 9, pp. 31-39 (2000); 1otier, B .; Voiaa, K.N .; At. 1. C1t. Νυίτ. 71, p. 1530-1535 (2000); Mi, 1. 1. e! A1 .; 1. Nit. Nureyekyui 19, pp. 479-483 (2005)), which confirm this effect of calcium on blood pressure.

In the patent application of Germany No. EE 102005033630.2 describes the calcium-peptide component and its use as a means, including for regulating body weight and blood pressure.

For the reasons listed above, the prevention of diabetes mellitus caused by metabolic disorders (type II diabetes) is a health policy issue that is of increasing interest to both the pharmaceutical and food industries.

Therefore, it is an object of the present invention to provide a product that can be used to prevent type II diabetes mellitus.

It was completely unexpected and absolutely unpredictable for specialists that the calcium-peptide component described in the German patent application No. EE 102005033630.2, developed as a means for regulating body weight and blood pressure, according to the invention can significantly slow down the occurrence of diabetes mellitus caused by metabolic disorders (diabetes Type II), or that when using the calcium-peptide composition according to the invention, a very noticeable improvement in the clinical picture of the disease can be achieved Nia type II diabetes mellitus.

Therefore, the subject of the present invention is the use of a calcium peptide composition comprising at least one calcium salt, at least one casein phosphopeptide (CPP) and at least one glycomacropeptide (GMF), for the manufacture of an agent for the prophylaxis and / or treatment of type II diabetes mellitus . When taking this composition, it is possible to significantly reduce the likelihood of type II diabetes mellitus (antidiabetogenic effect).

The invention is characterized in that the calcium peptide composition comprising at least one calcium salt and casein phosphopeptide (CPP) and / or glycomacropeptide (GMF) is supplied to the body with calcium and peptide (s) in an appropriate form suitable for prophylaxis and / or treatment diabetes mellitus. A more detailed description of the calcium-peptide component can be taken from the German patent application No. EE 102005033630.2, the full disclosure of the contents of which is included in this application by reference to it.

Caseins as proteins of natural origin are an integral part of dairy products, which are about 20% composed of whey proteins and about 80% of caseins. The calcium contained in milk is bound by caseins.

Caseins have the ability to bind large amounts of calcium. Due to this, calcium is evenly distributed in the liquid, and not deposited at the bottom of the vessel in the form of thick. The disadvantage of caseins is that they precipitate at an acidic pH, so that casein bound

- 1 016545 calcium is not suitable for acidic foods.

Various research groups over the past years have been studying the calcium binding of casein in more detail, and the mechanism of action of calcium-binding peptides has been discovered. It has been found that certain regions of caseins are particularly well bound by calcium and that these regions have phosphate groups bound to protein. In the process of casein hydrolysis, among other things, casein phosphopeptides (CPP) are formed, which bind calcium especially effectively. From a chemical point of view, CPP is a group of peptides derived from caseins or fragments of the latter and containing at least one phosphate group. Thanks to the use of casein phosphopeptides, it is now possible to obtain substantially transparent calcium solutions in which calcium associated with CPP does not precipitate to about pH 3. Such casein phosphopeptides are now commercially available (see, for example, CPP ΌΜν).

Glycomacropeptide (GMF) is released from caseins in the production of cheese under the action of rennet and after separation of the cheese clot remains in the so-called whey fraction. From a chemical point of view, the glycomacropeptide, as the hydrophilic part of kappa-casein, is a fragment of kappa-casein with the amino acid sequence 106-169. Therefore, it is also called caseinglicomacropeptide or just caseinacropeptide. The glycomacropeptide is found in 11 different genetic variants, the most common genetic variants being varieties A and B. In addition, glycomacropeptides may also contain carbohydrate chains linked by glycosidic bonds. Typically, approximately 30-50% of the glycomacropeptide contains glycosidically linked carbohydrate chains. The glycomacropeptide does not contain aromatic amino acids, and, in addition, as a rule, also contains a phosphate group that can bind calcium (in human and cow GMFs, one of the serine residues is usually phosphorylated, and this phosphate group can also be cleaved).

By mixing casein phosphopeptide with glycomacropeptide, substantially more stable calcium solutions are obtained, which, in addition to everything else, are also better absorbed physiologically.

Quite unexpectedly, it was found that the calcium-peptide composition according to the invention in experiments on animals found a property to reduce the incidence of diabetes. In rats of the so-called линии-line (ΖΌΡ = diabetes mellitus obesity), prone to genetically caused diabetes mellitus, it was possible to prove the protective effect that the calcium-peptide composition has.

Four groups of 16 ΖΌΡ-line rats in each were studied. For this, rats received, starting from the 2nd and the 6th week of life, a calcium-poor diabetic diet. Starting from the 6th week of life, individual groups of animals received (daily, for 26 days; data are based on the amount of solid feed): 1) feed without any additives (control group); 2) calcium supplementation with glycomacropeptide (3.6% Ca and 3.8 GMF); 3) calcium supplement with casein phosphopeptide (3.6% Ca and 2.0% CPP); 4) calcium supplementation with glycomacropeptide and casein phosphopeptide (3.6% Ca, 3.8 GMP and 2.0 CPP). These doses correspond to the daily doses indicated in the table below for humans. Throughout the study period, 9 out of 16 rats from the control group (group 1) developed diabetes mellitus, while in groups 2 and 3 the disease appeared in only three of 16 animals, and in group 4 only in one of 16 animals had diabetes mellitus detected. Thus, all varieties of the calcium-peptide composition showed an antidiabetogenic effect.

Table 1. The study of the antidiabetogenic effect in rats of the линии-line, during which rats, starting from the 6th week of life, received a dietary supplement daily for 26 days

Food supplement (based on the amount of dry feed) The number of rats with diabetes Group 1 Did not receive 9/16 Group 2 3.6% Ca + 3.8% GMF 3/16 Group 3 3.6% Ca + 2.0% CPP 3/16 Group 4 3.6% Ca + 2.0% CPP + 3.8 GMP 1/16

- 2 016545

The same effect was found in people (in the course of clinical studies conducted over a period of 6 months in 60 patients) who are prone to pronounced metabolic syndrome.

Therefore, the invention relates to the use of a calcium peptide composition according to the invention as a (drug) agent for the manufacture of an agent for the prevention of diabetes mellitus.

Interestingly, this effect of the calcium peptide composition according to the invention can also be achieved when calcium was used in combination with one of the two peptides (glycomacropeptide or casein phosphopeptides). However, in the case of combined use of calcium with both peptides, the effect is more pronounced. For none of the above combinations, referred to herein as a calcium peptide composition, such an effect has not been described elsewhere.

One of the newest scientific studies (Ney, 1. 1 .; Λροΐςνίδΐ. A.A .; Xi, X .; KhushChouu, Μ. Μ .; Νοίΐ8oi, 1.K .; Staitee, S.K .; K1t, 8. K .; No. 1ite, 443, pp. 345-349 (2006)) shows that calcineurin is crucial for the state of insulin-producing beta cells of the pancreas. Calcineurin is a protein that regulates the activity of ten genes that are usually associated with the picture of the disease in diabetics. When blocking the intake of calcineurin, there is no adaptation of the number of beta cells that are so important for controlling blood sugar during growth. In addition to this, the amount of insulin produced by existing beta cells is also reduced. However, there is no indication that calcium, or rather, the form in which it enters the body, is a decisive factor in the treatment and / or prevention of diabetes.

The mass ratio between at least one calcium salt (in terms of calcium) of at least one casein phosphopeptide and at least one glycomacropeptide is preferably 1-5: 0.5-2.5: 1.5-7.5. If only a combination of calcium salt with casein phosphopeptide is used, then the weight ratio of at least one calcium salt and casein phosphopeptide is preferably 1-5: 0.5-2.5, respectively. When using a combination of at least one calcium salt and glycomacropeptide, their weight ratio is preferably 1-5: 1.5-7.5. Even more preferably, the mass ratio should be Ca: CPP: GMF = 2-3: 0.75-1.25: 2-4. In the most preferred case, it is 2.5: 1: 3.

In an embodiment according to the invention, the addition of minerals and / or trace elements to the calcium peptide composition is entirely feasible. Without limiting the essence of the invention as possible mineral substances or trace elements can be used: magnesium, zinc, iron, copper, molybdenum, selenium, fluorine, manganese, chromium, iodine, potassium, sodium, chlorides, carbonates, phosphates. To avoid the problems of calcium deposition in blood vessels, magnesium, for example, can be added to the calcium peptide composition of the invention. In this case, you can add any magnesium salts allowed for use by the legislation governing the production and sale of food products. As a daily dose, a maximum of 250 mg, in terms of magnesium, is recommended, which corresponds to the recommended daily dose for an adult (KEA = recommended daily dose).

Vitamins are also preferably added to the calcium peptide composition of the invention. Without limiting the essence of the invention, some possible vitamin supplements can be named here: vitamins A, B ₁₂ B ₂ , B ₆ , B ₁₂ , C, Ό, E and K, niacin (B ₃ ), pantothenic acid (B ₅ ), biotin ( B ₇ ) and folic acid (B ₉ ). A particular advantage is the addition of vitamin Ό, which, among others, is responsible for the absorption of calcium in the small intestine.

Another preferred use of the calcium peptide composition according to the invention is to add soluble ballast materials therein. Without limiting the essence of the invention, for example, the following ballast substances can be added: oligofructose, inulin, phytosterols, galactooligosaccharides, polydextrose, cellulose, pectin, starch products, xyloooligosaccharides, guar gum and / or beta-glucans. Most preferably, oligofructose and / or phytosterols are added.

As calcium salts are suitable all permitted for use by the legislation governing the production and sale of food products and / or calcium-containing salts approved for use in the pharmaceutical industry. Without limiting the essence of the invention, some of them may be mentioned here: calcium carbonate, calcium chloride, calcium citrate, calcium gluconate, calcium glycerophosphate, calcium lactate, calcium orthophosphate, calcium oxide and / or calcium hydroxide.

The calcium peptide composition according to the invention can be used as an additive to food products, as well as a food supplement or pharmaceutical preparation.

In general, the calcium peptide composition can be used to prepare the products or products in liquid, solid, powder, compressed, or any other form. The form of its application also depends on the state of aggregation of the product. It is preferably taken ne

- 3 016545 rorally. In the same way, its intragastric (directly into the stomach), nasogastric (via a probe through the nose into the stomach), parenteral (directly into the body, bypassing the gastrointestinal tract) or intravenous (directly into the vein) administration is possible.

Thus, products intended for dietary nutrition can be made. It is also possible to obtain products related to pharmaceuticals or drugs for self-medication.

The calcium peptide composition according to the invention can be used in a variety of forms. Without limiting the essence of the invention, the complex according to the invention is suitable, in particular, for use as a sweetener, in powder, tablet or pressed form, in the form of a bar, jelly or emulsion.

Typical uses are in fruit juices, cottage cheese and herbal mixes, whey drinks, desserts, ice cream, fruit bars, tablets, capsules, sprays, or powders in a single dose package.

Full disclosure of the essence of all the above and below in the text of applications, patents and publications is included in the present application in the form of a reference.

And without further justification, we can proceed from the fact that a specialist can use the above description in the broadest sense. Therefore, preferred embodiments and examples should be taken only as descriptive, and by no means as a restrictive disclosure of the invention.

Example 1. Intended for use according to the invention, the calcium peptide composition may have the composition shown in table 2 below (as an example, the recommended daily dose for humans).

Table 2. Possible composition of the calcium peptide composition

Individual component Mass ratio Example (daily dose) Calcium salt, e.g., four-water hydrate about 2.5 4.76 g Three Calcium Citrate Casein phosphopeptide * about 1 2.72 g Glycomacropeptide * about 3 5.0 g

* Casein phosphopeptide and / or glycomacropeptide may be present either individually or in combination.

The calcium peptide composition provided for use according to the invention can be added in powder form to individual packages, for example yogurt or fruit juices.

Example 2. Of the following prescription components (weight ratios are indicated), a compress is provided for use according to the invention, the composition of which includes a calcium peptide composition:

72.75% sorbitol 10% tricalcium citrate tetrahydrate 12% glycomacropeptides 4% casein phosphopeptides 0.5% magnesium stearate 0.5% liquid release wax 0.25% separating wax

Example 3. The formulation of the calcium-peptide composition as an integral part of a food supplement for children over the age of 6 years (analytical values are given) per one daily dose (which can also be taken in parts): see table. 3.

The form of application may, for example, be as follows: powder (mixture), tablets (compressible), concentrate (liquid, in aqueous solution), capsules (with a shell of gelatin), portioned packets (powder, in 1/3 of the daily dose), etc.

Example 4. The formulation of the calcium peptide composition as part of a dietary supplement for adults (analytical values are given) per one daily dose (which can also be taken in parts): see table. 3.

The form of application may, for example, be as follows: powder (mixture), tablets (compress),

- 4 016545 concentrate (liquid, in aqueous solution), capsules (with a shell of gelatin), portioned packets (powder, in 1/3 of the daily dose), etc.

Example 5. The formulation of the prebiotic calcium-peptide composition as an integral part of a dietary supplement for adults (analytical values are given) per one daily dose (which can also be taken in parts): see table 3.

The form of application may, for example, be as follows: powder (mixture), tablets (compressible), concentrate (liquid, in aqueous solution), capsules (with a shell of gelatin), portioned packets (powder, in 1/3 of the daily dose), etc.

Table 3. The formulations of the calcium peptide composition in accordance with examples 3, 4 and 5

Individual component Example 3 daily dose (analytical value) Example 4 daily dose (analytical value) Example 5 daily dose (analytical value) Calcium (as tricalcium citrate four-hydrate) 4,5 g 4.8 g 4.8 g Casein phosphopeptides 2.5 g 2.8 g 2.8 g Gly Comacropeptide 4.8 g 5.2 g 5.2 g Galactooligosaccharides - - 5.0 g Iron 220 mcg 360 mcg 180 mcg Zinc 160 mcg 240 mcg 240 mcg Copper 20 mcg 40 mcg 20 mcg Manganese 50 mcg 30 mcg 30 mcg Chromium 0.75 mcg 0.2 mcg 0.2 mcg Fluoride 10 mcg 6 mcg 6 mcg Iodine 3 mcg 5 mcg 5 mcg Molybdenum 2 mcg 0.6 mcg 0.6 mcg Selenium 0.5 mcg 0.4 mcg 0.4 mcg Vitamin A 16 mcg 21 mcg 21 mcg Vitamin Βι 20 mcg 45 mcg 45 mcg Vitamin B ₂ 20 mcg 48 mcg 48 mcg Vitamin _B 20 mcg 48 mcg 48 mcg Vitamin B12 0.08 mcg 0.08 mcg 0.08 mcg Vitamin C 2 mg 3 mg 3 mg Vitamin oz 0.14 mcg 0.3 mcg 0.3 mcg Vitamin E 240 mcg 300 mcg 300 mcg Biotin 2 mcg 4 mcg 4 mcg Ca-O-pantothenate 0.17 mcg 0.24 mcg 0.24 mcg Vitamin K | 1.4 mcg 2.3 mcg 2.3 mcg Folic acid 5.5 mcg 10 mcg 10 mcg Niacinamide 270 mcg 360 mcg 360 mcg

CLAIM

Claims (6)

1. The use of a calcium peptide composition comprising at least one calcium salt, at least one casein phosphopeptide (CPP) and at least one glycomacropeptide (GMF) for the manufacture of an agent for the prevention and / or treatment of type II diabetes mellitus. 2. The use of the calcium peptide composition according to claim 1, characterized in that the mass ratio between the calcium salt, casein phosphopeptide and glycomacropeptide is 1-5: 0.5-2.5: 1.5-7.5. - 5 016545 3. The use of the calcium-peptide composition according to claim 1 or 2, characterized in that mineral substances, trace elements and / or vitamins are added to it. 4. The use of the calcium peptide composition according to claims 1 to 3, characterized in that soluble ballast substances, in particular oligofructose, phytosterols and / or galactooligosaccharides, are added to it. 5. The use of the calcium peptide composition according to claims 1 to 4, characterized in that the calcium salt is calcium carbonate, calcium chloride, calcium citrate, calcium gluconate, calcium glycerophosphate, calcium lactate, calcium orthophosphate, calcium oxide and / or hydroxide calcium. 6. The use of a calcium peptide composition according to one of claims 1 to 5 as an additive to food products, food additives or pharmaceutical preparations. Eurasian Patent Organization, EAPO Russia, 109012, Moscow, Maly Cherkassky per., 2