DE102006052560B4 - Anti-diabetogenic calcium peptide composition - Google Patents

Abstract

Use of a calcium-peptide composition obtainable from
At least one calcium salt,
At least one caseinophosphopeptide (CPP) and
At least one glycomacropeptide (GMP)
for the prevention and / or treatment of diabetes (type II).

Description

The The invention relates to the use of a calcium-peptide composition for the prevention of a diabetic metabolism.

The Preventing such a metabolic condition, which already in the early years of childhood begins in man, and in consequence to an increased frequency lead from diabetes can, today is one of the most important goals, since this disease, which also due to malnutrition with triggered can be, a typical civilization disease, in particular in Europe and the US, with an increasing number of patients (in By 2010 there will be approximately 33 million people in Europe).

Calcium has been increasingly discussed in recent years in the scientific literature in the context of weight control in obese people. Various mechanisms have been used to explain this. On the one hand, the effect of calcium on a hormone-like action is described (Zemel, MB, J. Am Coll Nutr 21, pp. 146-151 (2002)). This principle of action is among other things in the patents US 6,384,087 B1 or EP 1 343 390 A2 described.

It It is also assumed that calcium through the formation of lime soap in the intestine prevents the absorption of fats and thus to a lower absorption of fat from the intestine (Jacobsen, R .; Lorenzen, J.K .; Toubro, S .; Krog-Mikkelsen, I .; Astrup, A .; Intern. J. Obesity 29, pp. 292-301 (2005)).

Further It is pointed out in the literature that calcium is always with Dairy products must be given together, if so a weight reduction should be achieved. However, there are also works that show that a use of dairy products does not necessarily lead to success (Gunther, C.W., et al., Amer J. Clin Nutr 81, pp. 751-756 (2005)).

The Previously mentioned weight control by calcium is used in medical Circles also in the overall picture of the so-called metabolic syndrome discussed. Among other things, it plays the regulation of blood pressure a role. A consequence of the disease is the metabolic syndrome the disease of diabetes (type II). It was funded by different research groups examined whether the regular dose Calcium also has a lowering effect on increased blood pressure may have. There are several studies (McCarron, THERE.; Reusser, M.E .; J. Amer. Coll. Nutr., 18, pp. 398-405 (1999); Bosticck, R.M. et al .; Arch. Fam. Med., 9, pp. 31-39 (2000); Jorde, R .; Bonaa, K.H .; At the. J. Clin. Nutr. 71, pp. 1530-1535 (2000); Mu, J.J. et al .; J. Hum. Hypertension 19, p. 479-483 (2005)), who have confirmed this effect of calcium on blood pressure.

The DE 10 2005 033 630 A1 describes a calcium-peptide component and its use as agents for, among other things, regulation of body weight and blood pressure.

The US 6,384,087 91 B1 discloses, inter alia, a method for the treatment of obesity in general, in which the administration of calcium, the serum insulin level is normalized.

The WO 02/052954 A2 describes a composition for the treatment of bone, which also contains calcium, caseinoglycomacropeptide and caseinophosphopeptide among other constituents.

From the US 2003/0008810 A1 a composition is known which contains, inter alia, a glycomacropeptide and optionally calcium. This composition is used to create a sense of satiety. Among other things, this composition is described as helpful or supportive of type II diabetes.

The WO 03/074129 A1 discloses a weight control and obesity treatment composition comprising a casein fragment 106-169 as a protein source and calcium.

The WO 01/37850 A2 describes the use of a milk protein hydrolyzate, particularly a caseinoglycomacropeptide in the form of a calcium salt, for the treatment of diabetes.

In the CN 1395870 A For example, a composition containing calcium lactate as well as hydrolyzed calcium is disclosed for the prevention and treatment of diabetes.

For the reasons mentioned above, the prevention of metabolic diabetes (Dia betes type II) is a public health problem that is increasingly affecting both the pharmaceutical and food industries.

task the present invention is therefore to develop a product that for prevention of diabetes (type II) can be used.

It was completely surprising and in no way foreseeable by those skilled in the art that the calcium-peptide component, which has been developed as a body weight and blood pressure regulator and which has been used in the DE 10 2005 033 630 A1 According to the invention, the development of metabolic diabetes (type II) can be markedly reduced, or a very significant decrease in the type II diabetes can be achieved with the calcium-peptide composition according to the invention.

• – mindestens einem Calciumsalz,
• – mindestens einem Caseinophosphopeptid (CPP) und
• – mindestens einem Glycomakropeptid (GMP)

zur Prävention und/oder zur Behandlung von Diabetes (Typ II). Durch die Darreichung dieser Zusammensetzung ist es möglich, die Entstehung der Diabetes (Typ II) deutlich zu unterdrücken (anti-diabetogene Wirkung).The present invention therefore provides the use of a calcium-peptide composition obtainable from

• At least one calcium salt,
• At least one caseinophosphopeptide (CPP) and
• At least one glycomacropeptide (GMP)

for the prevention and / or treatment of diabetes (type II). By providing this composition, it is possible to significantly suppress the onset of diabetes (type II) (anti-diabetogenic effect).

The invention is characterized in that a calcium-peptide composition containing at least one calcium salt and CPP and / or GMP provides calcium and peptide (s) in a suitable form for the prevention and / or treatment of diabetes to effect. A more detailed description of the calcium-peptide component can be found in patent application no. DE 10 2005 033 630 A1 are found, the entire disclosure of which is incorporated herein by reference.

caseins are as natural occurring proteins a part of the milk proteins, which is about 20% from whey proteins and about 80% casein. To the Casein becomes mainly the calcium is bound to the milk. These are capable of large quantities to bind to calcium. As a result, the calcium is even in the liquid distributed and does not store on the ground in the form of a sediment from. However, the caseins have the disadvantage that they at acidic pH precipitated, so that bound casein calcium unsuitable for acidic products is.

Various scientific research groups have in recent years investigated the binding of calcium to casein more closely and thereby the Discovered principle of calcium-binding peptides. It turned out certain sections of the caseins especially calcium bind well and that these sections have protein-bound phosphate groups feature. Become hydrolyzed caseins, u arise. a. Caseinophosphopeptide (CPP), which bind calcium particularly well. Chemically speaking CPP is a group of peptides derived from caseins or derived from fragments of the caseins and the at least contain a phosphate group. Through the use of caseinophosphopeptides can Today, one achieves largely clear calcium solutions in which the bound CPP-calcium does not precipitate to about pH 3. Such Caseinophosphopeptides are commercially available today (eg. CPP DMV).

Glykomacropeptid (GMP) is used in the production of cheese by the action of rennet released from the caseins and is after cheese production in the so-called whey fraction. Chemically, glycomacropeptide as the hydrophilic part of κ-casein a fragment of κ-casein with the amino acid sequence 106 to 109. It is therefore also called caseinoglyocmacropeptide or caseinomacropeptide. Glycomacropeptide comes in 11 different genetic variants, with A and B the most common genetic variants are. About that can out Glycomacropeptides also glycosidically linked carbohydrate chains contain. As a rule, about 30-50% of GMP contains glycosidically linked carbohydrate chains. Contains glycomacropeptide no aromatic amino acid and above also usually a phosphate group, on the Calcium can be bound (in GMP of man and cow is in the Usually one of the serine residues is phosphorylated, this phosphate group but can also be split off).

A Mixture of caseinophosphopeptide and glycomacropeptide yields essential more stable calcium solutions, which are also physiologically better usable.

Surprisingly it was found that the calcium-peptide composition according to the invention in animal experiments a reducing property for the development of diabetes having. In rats (so-called ZDF rats, ZDF = Zucker-diabetic-fatty), that are prone to a genetic development of diabetes, was able to demonstrate a protective effect of the calcium-peptide composition become.

Four groups of 16 ZDF rats each were studied. These rats were fed from the 2nd week of life and up to the 6th week of life with a low-calcium, diabetogenic diet. From the 6th week of life, the individual groups received (daily, for 26 days, based on the amount of solid food): 1. no food supplement (control), 2. an addition of calcium + glycomacropetide (3.6%) Ca and 3.8% GMP), 3. an addition of calcium + caseinophosphopeptide (3.6% Ca and 2.0% CPP), 4. an addition of calcium + glycomacropetide + caseinophosphopeptide (3.6% Ca and 3, 8% GMP and 2.0% CPP). These doses correspond to the daily doses given to humans in the table below. During the study period, 9 out of 16 control rats (group 1) developed diabetes, in group 2 and 3 only diabetes was detected in 3 out of 16 rats and in group 4 in only 1 out of 16 rats. Thus, all variants of the calcium-peptide composition proved to be anti-diabetogenic. Table 1: Investigation of the anti-diabetogenic effect in ZDF rats, wherein the rats were supplemented daily for 26 days from the 6th week of life. Nutritional supplement (based on the amount of solid food) Number of rats with diabetes Group 1 none 9/16 Group 2 3.6% Ca + 3.8% GMP 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

The same effect could be similarly in patients (in a clinical Study about 6 months, each with 60 persons), which are indicative of the Metabolic syndrome tend.

The The invention therefore relates to the use of the calcium-peptide composition according to the invention as a (drug) agent for the preparation of an agent for preventing the onset of diabetes.

Interestingly, this effect could be the effect of the calcium-peptide composition according to the invention can also be achieved when using Calci in combination with just one of both peptides (G1ycomakropeptid or caseinophosphopeptides) used has been. The effect of combining calcium with both peptides is more pronounced. For no the aforementioned combinations, referred to herein as calcium-peptide composition Such an effect has hitherto been described.

A recent scientific study (Heit, J.J., Apelqvist, A.A .; Gu, X .; Winslow, M.M .; Neilson, J.R .; Crabtree, G.R .; Kim, S. K .; Nature, 443, pp. 345-349 (2006)) shows that calcineurin has a decisive influence on the health of insulin-producing pancreatic beta cells Has. Calcineurin is a protein that regulates ten genes that interact with be associated with the disease in diabetics. A Blocking the intake of calcineurin prevents growth adapted the number of beta cells to control blood sugar become. additionally The amount of beta cells produced by existing beta cells decreases Insulin. An indication that the calcium or the "form" in the it to the body disposal is the decisive factor in the treatment and / or prevention diabetes is not evident in this study.

The weight ratio between the at least one calcium salt (based on the calcium), the at least one caseinophosphopeptide and the at least one glycomacropeptide is preferably 1-5: 0.5-2.5: 1.5-7.5. If only a combination of calcium salt and CPP is present, then the weight ratio of the at least one calcium salt and CPP is accordingly preferably 1-5: 0.5-2.5. For a combination of at least one calcium salt and GMP, it is then preferably 1-5: 1.5-7.5. Be more preferably, the ratio Ca: CPP: GMP is 2-3: 0.75-1.25: 2-4. Most preferably, it is 2.5: 1: 3.

In an embodiment of the invention is the addition of minerals and / or trace elements to the Calcium peptide composition imaginable. Without restriction The public are here as possible minerals or trace elements magnesium, zinc, iron, copper, molybdenum, selenium, Fluoride, manganese, chromium, iodine, potassium, sodium, chloride, carbonate, Phosphate. To avoid problems of calcium deposition in the blood vessels, may the calcium-peptide composition of the invention for example, in addition Magnesium be added. In doing so, everyone is allowed under food law allowed magnesium salts are added. The daily amount becomes one Amount of maximum 250 mg magnesium recommended; that corresponds to the Recommended daily dose of an adult human, RDA (Recommended Daily allowance).

Preferably, vitamins are also added to the calcium-peptide composition according to the invention. Without loss of generality, vitamin A, B ₁ , B ₂ , B ₆ , B ₁₂ , C, D, E and K, niacin (B ₃ ), pantothenic acid (B ₅ ), Biotin (B ₇ ) and folic acid (B ₉ ). Vitamin D is particularly preferably added, which is partly responsible for the absorption of calcium in the small intestine.

Also the addition of soluble Fiber is a preferred embodiment for the use according to the invention the calcium-peptide composition. Without restriction the general public For example, the following dietary fiber is added: Oligofructose, Inulin, phytosterols, galactooligosaccharides, polydextrose, cellulose, Pectin, starch derivatives, Xylooligosaccharides, guar gum and / or β-glucans. Preference is given to oligofructose, and / or phytosterols added.

When Calcium salts are all food and / or pharmaceutical approved calcium-containing salts in question. Without limitation Generality can be mentioned here: calcium carbonate, calcium chloride, Calcium citrates, calcium gluconate, calcium glycerophosphate, calcium lactate, Calcium orthophosphates, calcium oxide and / or calcium hydroxide.

The calcium-peptide composition according to the invention Can be used both as an additive in food as well as a dietary supplement or as a pharmaceutical preparation be used.

Basically the calcium-peptide composition for the preparation of agents or Products in liquid, solid, powdery, compacted or any other state of aggregation used become. The aggregate state of the product also results in the Application form. The oral application is preferred. Likewise possible but also the intragastric (directly in the stomach), the nasogastric (over a Probe through the nose into the stomach), the parenteral (directly into the body bypassing the gastrointestinal tract) or the intravenous (direct in a blood vein) application.

So can Products are made in the dietary food sector be used. It can but also products that are pharmaceutical sector Products or self-medication.

The calcium-peptide composition according to the invention is versatile. Without restriction of generality is the composition is particularly suitable for use as candy, powder, Tablets, compacted forms, bars, jellies or emulsions.

typical Application examples are the use in fruit juices, quark and yoghurt dishes, whey drinks, desserts, Ice cream, fruit bar, Tablets, capsules, sprays or single-dose powder packaging.

The full Disclosure of all applications listed above and below, patents and publications are incorporated by reference into this application.

Also without further explanations It is assumed that a professional has the above description to the fullest extent.

The preferred embodiments and examples are therefore merely descriptive, not by any means to understand as in any way limiting revelation.

example 1

• *Caseinophosphopeptid und/oder Glycomakropeptid können jeweils allein oder in Kombination bereit gestellt werden.

The calcium-peptide composition intended for use according to the invention may be composed according to the following Table 2 (for example, the recommended daily dose for humans is given). Table 2: possible composition of the calcium-peptide composition Single component weight ratio Example (daily dose) Calcium salt z. B. tricalcium citrate tetrahydrate about 2.5 4.76 g Caseinophosphopeptid * approx. 1 2.72 g glycomacropeptide * about 3 5.0 g

• Caseinophosphopeptide and / or glycomacropeptide may each be provided alone or in combination.

The for use according to the invention provided calcium-peptide composition is called powdered Mixture added in individual packaging, for example, yogurt or fruit juices.

Example 2

From the following formulation components (stated are the parts by weight), a compressed preparation intended for use according to the invention is prepared containing the calcium-peptide composition: 72.75% sorbitol 10% Tricalcium citrate tetrahydrate 12% glycomacropeptides 4% Caseinophosphopeptide 0.5% magnesium stearate 0.5% liquid release wax 0.25% Trennwachs

Example 3:

recipe for one Calcium-peptide composition as part of a dietary supplement for children from 6 years (data as analysis values) related to a daily amount (which may also be administered in parts): see Table 3.

The Dosage form can z. As: powder (mixture), tablets (Comprimat), Concentrate (liquid in aqueous Solution), Capsule (shell made of gelatin), sachets (powder, 1/3 of the daily amount), etc.

Example 4:

recipe for one Calcium-peptide composition as part of a dietary supplement for adults (Details as analysis values) based on a daily amount (which are also administered in parts can): see Table 3.

The Dosage form can z. As: powder (mixture), tablets (Comprimat), Concentrate (liquid in aqueous Solution), Capsule (shell made of gelatin), sachets (powder, 1/3 of the daily amount), etc.

Example 5:

recipe for one prebiotic calcium-peptide composition as part of a Dietary supplement for adults (Data as analysis values) related to a daily amount (which also can be administered in parts): see Table 3.

The dosage form may, for. B.: powder (mixture), tablets (compressed), concentrate (liquid in aqueous solution), capsule (shell of gelatin), sachets (powder, each 1/3 of the daily amount), etc. Table 3: Formulations of the calcium-peptide composition according to Examples 3, 4 and 5 Single component Example 3 Daily amount (analysis) Example 4 daily amount (analysis) Example 5 daily amount (analysis) Calcium (as tricalcium citrate tetrahydrate) 4.5 g 4.8 g 4.8 g Caseinophosphopeptide 2.5 g 2.8 g 2.8 g glycomacropeptide 4.8 g 5.2 g 5.2 g Galactooligosacharide - - 5.0 g iron 220 μg 360 μg 180 μg zinc 160 μg 240 μg 240 μg copper 20 μg 40 μg 20 μg manganese 50 μg 30 μg 30 μg chrome 0.75 μg 0.2 μg 0.2 μg fluoride 10 μg 6 μg 6 μg iodine 3 μg 5 μg 5 μg molybdenum 2 μg 0.6 μg 0.6 μg selenium 0.5 μg 0.4 μg 0.4 μg Vitamin A 16 μg 21 μg 21 μg Vitamin B ₁ 20 μg 45 μg 45 μg Vitamin B ₂ 20 μg 48 μg 48 μg Vitamin B ₆ 20 μg 48 μg 48 μg Vitamin B ₁₂ 0.08 μg 0.08 μg 0.08 μg vitamin C 2 mg 3 mg 3 mg Vitamin D ₃ 0.14 μg 0.3 μg 0.3 μg Vitamin E 240 μg 300 μg 300 μg biotin 2 μg 4 μg 4 μg Ca-D-pantothenate 0.17 μg 0.24 μg 0.24 μg Vitamin K ₁ 1.4 μg 2.3 μg 2.3 μg folic acid 5.5 μg 10 μg 10 μg niacinamide 270 μg 360 μg 360 μg

Claims (6)

Use of a calcium-peptide composition available out - at least a calcium salt, - at least a caseinophosphopeptide (CPP) and - at least one glycomacropeptide (GMP) for prevention and / or for the treatment of diabetes (type II). Use of the calcium-peptide composition according to Claim 1, characterized in that the weight ratio between Calcium salt, caseinophosphopeptide and glycomacropeptide 1 to 5 too 0.5 to 2.5 to 1.5 to 7.5. Use of the calcium-peptide composition according to Claim 1 or 2, characterized in that minerals, trace elements and / or vitamins are added. Use of the calcium-peptide composition according to one of the claims 1 to 3, characterized in that soluble fiber, in particular Oligofructose, phytosterols and / or galactooligosaccharides added become. Use of the calcium-peptide composition according to one of the claims 1 to 4, characterized in that food law and pharmaceutically approved calcium salts are used, in particular Calcium carbonate, calcium chloride, calcium citrate, calcium gluconate, Calcium glycerophosphate, calcium lactate, calcium orthophosphate, calcium oxide and / or calcium hydroxide. Use of the calcium-peptide composition according to one of the claims 1 to 5 as an additive in food, in dietary supplements or in pharmaceutical preparations.