Protein substitution composition

Abstract

Composition, especially for protein replacement in renal insufficiency, characterized by that the composition is in liquid form and (a) Whey protein in an amount of 15 to 50% (w / v), and (b) 3-Hydroxy-3-methylbutyric acid in an amount of 0.01 to 3% (w / v), each relating to the composition, contains.

Description

[0001] The present invention relates to the technical field of food supplements or foods for special medical purposes, in particular for the therapeutic treatment of diseases or for a balanced diet.

[0002] In particular, the present invention relates to a composition suitable for protein substitution in cases of renal insufficiency, especially in dialysis patients.

[0003] Furthermore, the present invention relates to a composition for use in the therapeutic treatment of protein deficiency diseases, hyperphosphatemia and secondary hyperparathyroidism.

[0004] Furthermore, the present invention relates to the use of a composition as a food supplement or for substituting the increased protein requirement in cases of renal insufficiency.

[0005] Finally, the present invention relates to the use of a composition for the therapeutic treatment of protein deficiency diseases, hyperphosphatemia and secondary hyperparathyroidism.

[0006] The human body normally excretes waste products present in the blood and those produced by metabolic processes, as well as excess electrolytes and minerals, via the kidneys. However, in many people, this excretion of waste products and excess electrolytes and minerals is impaired. If kidney dysfunction leads to insufficient excretion of waste products or excess electrolytes and minerals, this is referred to as renal insufficiency, which, depending on its severity, is associated with a significant loss of quality of life and can even pose a risk to life and health. If kidney function ceases completely or almost completely, end-stage renal failure is present, and the patient requires renal replacement therapy, the mechanical removal of unwanted substances from the bloodstream.Most patients with kidney failure receive hemodialysis. A small percentage of patients are treated with peritoneal dialysis.

[0007] In Germany, approximately 80,000 patients are currently receiving dialysis treatment. The majority of these patients have no residual urine output or can only produce small amounts of residual urine with negligible concentration. This means that the waste products generated by metabolic processes can no longer be excreted, and only water is excreted, which is often insufficient, if it occurs at all.

[0008] In addition to waste products and excess water, the kidneys can also no longer excrete excess electrolytes or minerals. This is particularly critical with regard to the essential components phosphate and potassium contained in the blood: An excessively high concentration of potassium, known as hyperkalemia, leads to cardiac arrest, while an excessively high phosphate level in the blood, known as hyperphosphatemia, often leads to secondary hyperparathyroidism.

[0009] Since the natural homeostasis in the blood, i.e., the equilibrium of the natural internal environment, is disturbed by the lack of excretion, dialysis patients usually undergo dialysis three times a week, in which the concentration of the individual blood components is brought back to the target state, i.e., the concentrations present in the blood of healthy people.

[0010] However, dialysis patients have an increased protein requirement: While the protein requirement in the general population is approximately 0.8 g / kg body weight per day, the literature consistently states that the protein requirement for dialysis patients is 1.2 g / kg body weight per day, meaning that dialysis patients need about 50% more protein than the general population. Proteins are essential components of body cells and play a vital role in the blood as hormones, such as insulin or glucagon, or as transport media, such as erythrocytes or albumin.

[0011] The increased protein requirement is due to protein loss during dialysis. For example, some proteins, such as red blood cells and albumin, are destroyed by collisions with the surface structures of the plastic tubing and the dialyzer. Other proteins are broken down or fractured in the blood pump. Besides the loss of protein function, this is particularly evident in the fact that small proteins, especially short amino acid sequences—the so-called peptides—are removed from the blood in a concentration-dependent manner, since the dialyzer operates on the principle of osmosis. Finally, a small amount of blood always remains in the dialysis system, resulting in further protein loss. To compensate for this constant protein loss, dialysis patients must consume a larger amount of protein.

[0012] The problem here, however, is that protein from natural sources, such as that found in plant or animal products, usually only occurs in conjunction with phosphate, meaning that the phosphate is bound to the proteins. An excessively high concentration of phosphates in the blood, known as hyperphosphatemia, leads to secondary diseases and represents the biggest problem for patients with chronic kidney disease. Dialysis patients are particularly affected because, as previously mentioned, they have a protein requirement approximately 50% higher than the general population. This means that with sufficient protein intake, dialysis patients also ingest more phosphate, again approximately 50% more than the general population.

[0013] Healthy individuals excrete excess phosphate, such as that which can occur after consuming phosphate-containing foods—for example, cola—via the kidneys according to the homeostatic principle. This pathway is not available to patients with kidney failure, and especially not to dialysis patients. They can only inactivate free phosphate by binding it to calcium, but this lowers the calcium level in the blood serum. The reduced calcium level in the blood serum, however, leads to the activation or increased production of parathyroid hormone in the parathyroid glands, a condition known as secondary hyperparathyroidism. Parathyroid hormone mobilizes the body's own calcium reserves from bones and teeth, making calcium ions available in the bloodstream for the complex formation and precipitation of phosphate. This ongoing process leads to osteopathy and osteomalacia, i.e.,a softening of the bones, with reduced bone mass and a deterioration of the bone's microarchitecture with correspondingly reduced strength.

[0014] However, it is not only the continuous loss of calcium from bones and teeth that is problematic for the body, but also the resulting phosphate-calcium complexes. These complexes are deposited in the body's soft tissues—where they cause itching—and also in the arteries. This type of arteriosclerosis regularly leads to heart attacks and strokes. This process is exacerbated in patients with chronic kidney failure, especially dialysis patients, because vitamin D, the antagonist of parathyroid hormone, is produced in the skin under sunlight and then needs to be activated in the liver and kidneys. This activation process, however, is either absent or severely impaired in patients with chronic kidney failure.

[0015] While dialysis removes some phosphate from the blood, this is insufficient, as the following example illustrates: A 70 kg dialysis patient should consume 84 g of protein per day according to dietary recommendations. Protein sources contain an average of 17 mg of phosphate per gram of protein to be considered kidney-healthy. This value cannot be met with many dairy products, for example. Even if only 17 mg of phosphate were bound to the protein per gram, the patient would still be consuming approximately 1,428 mg of phosphate per day and about 10,000 mg of phosphate per week, of which only about 60 to 70% would be absorbed by the body. Dialysis, however, can remove approximately 1,000 mg of phosphate in a single session, meaning that with three treatments per week, 3,000 mg of phosphate can be removed from the blood.However, this is far from sufficient, so in practice phosphate binders are administered, which, if taken correctly and in a targeted manner, can limit phosphate absorption to approximately 40 to 50%. Even with these measures, however, an excess of approximately 800 to 1,600 mg of phosphate per week remains, which cannot be eliminated. For this reason, the diet of dialysis patients must be structured in such a way that the daily phosphate intake is limited to approximately 1,000 mg per day.

[0016] Since it is difficult to maintain this diet permanently with natural products without developing a protein deficiency, low-phosphate protein supplements are offered specifically for dialysis patients. These products are usually sold as a powder. The patient must measure the powder, mix or shake it with a little water, and then consume the mixture as a drink. While this type of protein supplementation is generally suitable for providing dialysis patients with low-phosphate proteins, it encounters numerous problems and obstacles in practice.

[0017] For example, most dialysis patients are over 70 years old and no longer physically able to dissolve the powder themselves, so they depend on assistance. If such assistance cannot be provided, the protein substitute cannot be prescribed for compliance reasons. Furthermore, the imprecise dosing using measuring spoons carries the risk of incorrect dosages.

[0018] Protein substitutes in powder form, known from the prior art, especially those based on milk components such as whey proteins, are often characterized by poor handling due to the water-binding properties of their ingredients. Excessive water binding can lead to uneven distribution, clumps of powder, and ultimately an unpleasant, slimy texture in the prepared oral nutritional supplement. Preparation often requires a blender, as a simple shaker cannot achieve uniform dissolution of the powder in the liquid or water. Elderly or physically impaired patients, in particular, are then unable to prepare the oral nutritional supplement without assistance. The high water binding ultimately makes it difficult to achieve a sufficiently high and therefore effective protein concentration in the formulations.

[0019] Besides pure protein supplements based on milk components, there are also a number of high-calorie combination products that constitute a complete diet. This means that, in addition to whey proteins, the nutritional product also contains energy sources in the form of carbohydrates or fats. However, this additional physiological energy value raises further problems. Firstly, some dialysis patients suffer from a pure protein deficiency, meaning that in this case it would be completely unnecessary to burden this patient group with additional calories; secondly, almost 50% of dialysis patients are diabetic.

[0020] Diabetes mellitus is a metabolic disease based on an absolute or relative insulin deficiency, resulting in high blood glucose concentrations, known as hyperglycemia. This promotes damage to blood vessels and thus represents a further trigger factor for heart attacks and strokes. Furthermore, high blood glucose levels lead to kidney damage and can therefore reduce any remaining diuresis. Other consequences can include nerve damage (polyneuropathy), vision loss, or diabetic foot with possible amputation. To minimize these complications, diabetics must adhere to a strict dietary regimen with regular blood glucose monitoring. Food products with a high glucose density are therefore contraindicated for diabetics.

[0021] In addition, there are also powdered protein preparations based on collagen hydrolysates, which in the medical field have so far been used almost exclusively for the prevention and treatment of osteoporosis.

[0022] German patent DE 10 2012 110 612 A1 describes a collagen hydrolysate produced by enzymatic hydrolysis of type B bone gelatin. The bone hydrolysate consists of peptides, at least 50% by weight of which have a molecular weight of 1,500 to 13,500 g / mol and a mean molecular weight of 4,000 to 8,000 g / mol. The collagen hydrolysate is used as an active ingredient to maintain or improve bone health, particularly for the prevention and / or treatment of osteoporosis. However, the proposed dosages are not suitable for dialysis patients. Furthermore, the peptide molecules are poorly absorbed by the body.

[0023] Another serious problem associated with kidney failure, and especially dialysis, is the skeletal muscle wasting that occurs in patients, combined with a loss of muscle mass, known as "protein wasting." To halt or at least delay muscle wasting and protein loss, patients can be given a higher dose of leucine. Leucine is an essential amino acid and plays a crucial role in muscle building and maintenance, as well as in healing processes. Unfortunately, leucine has a strongly acidic and unpleasant taste, which is why dietary supplements highly enriched with leucine are poorly tolerated by dialysis patients.

[0024] German patent DE 20 2014 105 602 discloses a protein composition based on collagen hydrolysate, which is low in phosphate, well tolerated, and absorbable. However, even this composition can only partially counteract the muscle protein loss and muscle wasting associated with renal insufficiency or dialysis.

[0025] While the use of the aforementioned collagen-based protein supplements offers some advantages, they are derived from native collagen, which primarily comes from animal byproducts such as skin, bones, and connective tissue. Therefore, these supplements are not suitable for people with dietary restrictions, such as vegetarians.

[0026] The present invention is therefore based on the objective of providing a composition which is suitable as a food supplement, in particular for protein substitution in patients with chronic renal insufficiency, whereby the disadvantages of the prior art described above are at least largely avoided or at least mitigated.

[0027] The present invention is specifically designed to provide a composition that ensures a reliable supply of low-phosphate protein to patients, particularly dialysis patients, and is also easy to use. Furthermore, the composition should be usable by the largest possible patient population, i.e., it should also be available to patients with other conditions, such as diabetes.

[0028] Another object of the present invention is to provide a composition which halts or at least slows down muscle protein loss and muscle wasting in renal insufficiency, particularly in dialysis patients.

[0029] Furthermore, another object of the present invention is to provide a protein preparation that is suitable for vegetarian diets and at the same time has the required high concentration of protein.

[0030] To solve the problem set out above, the present invention proposes a composition according to claim 1; further advantageous embodiments are the subject of the dependent claims.

[0031] A further subject matter of the present invention is the composition according to the invention for use in therapeutic treatments; further advantageous embodiments are the subject of the related dependent claims.

[0032] A further subject matter of the present invention is the use of the composition according to the relevant independent claim.

[0033] Finally, a further subject of the present invention is the use of the composition in therapeutic treatments.

[0034] It goes without saying that any special embodiments, designs or the like described below in relation to one aspect of the invention shall also apply to the other aspects of the invention without the need for explicit mention.

[0035] Furthermore, it should be noted that for all relative or percentage quantities mentioned below, especially those based on weight, these must be selected by a person skilled in the art in such a way that the sum of the respective ingredients, active substances, additives, excipients, or the like always results in 100% or 100% by weight. This is self-evident to a person skilled in the art.

[0036] Furthermore, it should be noted that all parameter information mentioned below, or similar data, can generally be determined or ascertained using standardized or explicitly specified determination procedures, or using determination methods that are familiar to the expert.

[0037] The subject matter of the present invention is therefore – according to a first aspect of the present invention – a composition, in particular for protein substitution in renal insufficiency, wherein the composition is in liquid form and (a) Whey protein in an amount of 15 to 50% (w / v), and (b) 3-Hydroxy-3-methylbutyric acid in an amount of 0.01 to 3% (w / v), each relating to the composition, contains.

[0038] For the purposes of the present invention, % (w / v) denotes the mass fraction of a substance relative to the volume of the composition.

[0039] As the applicant has discovered, the combination of whey protein and 3-hydroxy-3-methylbutyric acid according to the invention yields a highly concentrated protein preparation which, due to the 3-hydroxy-3-methylbutyric acid, exhibits a further improved effect with regard to muscle building and maintenance. In particular, the addition of 3-hydroxy-3-methylbutyric acid eliminates the need for further enrichment of the composition with leucine beyond that already contained in the whey proteins. Leucine is of particular importance for muscle building but has a strongly acidic and unpleasant taste. By using whey protein, preferably in combination with 3-hydroxy-3-methylbutyric acid, in the compositions, the positive effect of high leucine concentrations can be achieved without the adverse taste, thereby significantly improving patient compliance and acceptance.

[0040] 3-Hydroxy-3-methylbutyric acid, also known as beta-hydroxy-betamethylbutyrate, beta-hydroxyisovaleric acid, or HMB for short, is a metabolite of the essential amino acid leucine. Leucine is important for maintaining and building muscle tissue and supports healing processes. A high leucine intake is therefore particularly important for patients with renal insufficiency, especially dialysis patients. The beneficial effects of leucine are primarily due to its metabolite, 3-hydroxy-3-methylbutyric acid.

[0041] Within the scope of the present invention, it has been possible to provide a vegetarian protein supplement based on whey protein, characterized by its high protein content, particularly leucine (precursor) content, while being easy to handle and possessing excellent organoleptic properties. Leucine itself, as an essential amino acid with multifunctional physiological benefits, is of great importance. In the body, leucine activates muscle protein synthesis and is therefore, as mentioned above, important for muscle building and maintenance. Leucine can also promote muscle regeneration and performance. A high leucine content, achieved within the scope of the present invention through the combination of whey protein with HMB, can also improve the absorption of other proteins, which in turn can have a positive effect on health.

[0042] In particular, the compositions according to the invention exhibit excellent stability. Even after prolonged storage, they do not clump or form aggregates. Overall, the compositions are characterized by their pleasant, lump-free texture.

[0043] Having said that, particularly preferred embodiments of the present invention are described in detail below: Particularly good results with regard to compositions with high protein content are achieved according to the invention when the composition contains whey protein isolate, whey protein concentrate and / or whey protein hydrolysate.

[0044] Within the scope of the present invention, the term "protein" encompasses both "proteins" and "peptides," as well as their respective derivatives or fragments. "Proteins" are generally understood to be biological macromolecules composed of amino acids. Proteins differ from "peptides" in the length of their amino acid sequence or chain: peptides have a relatively short sequence of amino acid frequencies, while proteins can contain tens of thousands of amino acids. Molecules with fewer than 100 amino acids are usually referred to as peptides, while molecules with longer amino acid sequences are called proteins. This distinction is not rigid, however, and the terms are chosen according to the specific circumstances.

[0045] The various listed forms of whey protein are defined by their purity and processing. Whey protein concentrate has a protein content of approximately 70 to 80% by weight, and also contains significant amounts of lactose, fat, and minerals. Whey protein isolate, on the other hand, is further purified whey protein with a very high protein content, usually > 90%, and a significantly reduced amount of lactose and fat. It is highly purified whey protein. Whey protein hydrolysate, however, is whey protein that has been enzymatically or chemically broken down into smaller peptides. Therefore, it is not purer whey protein, but rather structurally modified, specifically hydrolyzed, whey protein.

[0046] According to a particularly preferred embodiment of the present invention, the composition contains whey protein isolate as the whey protein, wherein the whey protein isolate is preferably beta-lactoglobulin. According to a particularly preferred embodiment, the composition contains beta-lactoglobulin obtained from cow's milk as the whey protein isolate.

[0047] Beta-lactoglobulin is the main whey protein in ruminant milk and is a high-quality, acid-stable protein containing a variety of essential amino acids, especially leucine. Furthermore, beta-lactoglobulin offers 45% more leucine than conventional whey protein and thus significantly supports muscle protein synthesis. It is also typically tasteless, fat-free, and lactose-free, making it suitable for people with lactose intolerance. In addition to being extracted from whey, beta-lactoglobulin can also be produced through precision fermentation, enabling more sustainable production.

[0048] Furthermore, particularly good results are obtained within the scope of the present invention if the composition contains 3-hydroxy-3-methylbutyric acid in an amount of 0.05 to 2% (w / v), in particular 0.1 to 1% (w / v), preferably 0.12 to 0.18% (w / v), based on the composition.

[0049] According to a particular embodiment of the present invention, the composition contains 3-hydroxy-3-methylbutyric acid in the form of calcium 3-hydroxy-3-methylbutyrate (Ca-HMB).

[0050] Furthermore, the composition according to the invention is particularly low in phosphate and easy to handle. The composition according to the invention is therefore ideally suited for dietary supplementation, especially for protein replacement in cases of renal insufficiency and specifically for meeting the increased protein requirements of dialysis patients.

[0051] The composition according to the invention is a highly concentrated liquid protein concentrate which is easy to dose on the one hand, but contains as little liquid as possible on the other, since the amount of fluid ingested must be kept low, especially in patients with renal insufficiency.

[0052] The composition according to the invention is extremely easy to use, since it is already available as a ready-to-use, orally administered preparation and does not first have to be prepared by laboriously mixing a powder with water.

[0053] Within the scope of the present invention, it has proven advantageous for the composition to contain whey proteins, in particular whey protein isolate, in a concentration of 20 to 45% (w / v), particularly 25 to 40% (w / v), preferably 30 to 35% (w / v), based on the composition. The composition according to the invention is thus a highly concentrated protein concentrate, which enables an effective supply of proteins without requiring dialysis patients to ingest large quantities of fluid.

[0054] In general, the composition is an aqueous solution or dispersion of whey proteins. The composition according to the invention is preferably an aqueous dispersion or solution of whey proteins, which may optionally contain further substances, in particular excipients and additives. Because the composition according to the invention is in liquid form, especially as a solution or dispersion, compliance is significantly increased compared to products currently on the market, since the composition according to the invention is very easy to dose and, moreover, the patient or consumer has a consistently uniform product due to the ready-to-use solution or dispersion, whose sensory properties are always the same, i.e., it always produces the same mouthfeel and, for example, does not clump.

[0055] The presence of the composition according to the invention in a dispersion or solution thus significantly increases its acceptance among patients and consumers.

[0056] According to a preferred embodiment of the present invention, the composition contains whey protein in a concentration of 15 to 50% (w / v), in particular 20 to 40% (w / v), preferably 25 to 35% (w / v), based on the composition.

[0057] Particularly good results are obtained within the scope of the present invention if the composition contains the amino acid alanine in amounts of 0.1 to 5.0% (w / v), in particular 0.5 to 4.9% (w / v), preferably 1 to 2.5% (w / v), based on the composition.

[0058] Likewise, good results will be obtained if the composition contains the amino acid arginine in amounts of 0.01 to 3% (w / v), in particular 0.1 to 2% (w / v), preferably 0.5 to 1.3% (w / v), based on the composition.

[0059] According to the invention, the composition may contain the amino acid aspartic acid in amounts of 0.5 to 15% (w / v), in particular 1 to 10% (w / v), preferably 2 to 6% (w / v), based on the composition.

[0060] Within the scope of the present invention, it may also be provided that the composition contains the amino acid cysteine ​​in amounts of 0.01 to 4% (w / v), in particular 0.1 to 2% (w / v), preferably 0.5 to 1.5% (w / v), based on the composition.

[0061] Likewise, the composition may contain the amino acid glutamic acid in amounts of 1 to 15% (w / v), in particular 2 to 10% (w / v), preferably 3 to 8% (w / v), preferably 4 to 6% (w / v), based on the composition.

[0062] According to the invention, the composition may contain the amino acid glycine in amounts of 0.01 to 3% (w / v), in particular 0.05 to 2% (w / v), preferably 0.1 to 1% (w / v), based on the composition.

[0063] Furthermore, the composition may contain the amino acid histidine in amounts of 0.01 to 3% (w / v), in particular 0.05 to 2% (w / v), preferably 0.1 to 1% (w / v), based on the composition.

[0064] Again, good results are achieved when the composition contains the amino acid isoleucine in amounts of 0.5 to 8% (w / v), in particular 1 to 5% (w / v), preferably 1.5 to 2% (w / v), based on the composition.

[0065] Likewise, the composition may contain the amino acid leucine in amounts of 1 to 15% (w / v), in particular 2 to 10% (w / v), preferably 3 to 6% (w / v), based on the composition.

[0066] Furthermore, the composition may contain the amino acid lysine in amounts of 0.5 to 12% (w / v), in particular 1 to 10% (w / v), preferably 2 to 5% (w / v), based on the composition.

[0067] Within the scope of the present invention, it may also be provided that the composition contains the amino acid methionine in amounts of 0.1 to 3% (w / v), in particular 0.5 to 2% (w / v), preferably 0.8 to 1.3% (w / v), based on the composition.

[0068] According to the invention, the composition may contain the amino acid phenylalanine in amounts of 0.05 to 5% (w / v), in particular 0.1 to 3% (w / v), preferably 0.5 to 1.5% (w / v), based on the composition.

[0069] Furthermore, the composition may contain the amino acid proline in amounts of 0.05 to 6% (w / v), in particular 0.1 to 5% (w / v), preferably 1 to 3% (w / v), based on the composition.

[0070] Likewise, good results are achieved when the composition contains the amino acid serine in amounts of 0.05 to 5% (w / v), in particular 0.1 to 3% (w / v), preferably 0.5 to 1.5% (w / v), based on the composition.

[0071] According to the invention, the composition may contain the amino acid threonine in amounts of 0.05 to 6% (w / v), in particular 0.1 to 5% (w / v), preferably 1 to 3% (w / v), based on the composition.

[0072] Again, good results are achieved when the composition contains the amino acid tryptophan in amounts of 0.01 to 3% (w / v), in particular 0.1 to 2% (w / v), preferably 0.5 to 1.3% (w / v), based on the composition.

[0073] Furthermore, the composition may contain the amino acid tyrosine in amounts of 0.05 to 5% (w / v), in particular 0.1 to 3% (w / v), preferably 0.5 to 1.5% (w / v), based on the composition.

[0074] Furthermore, according to the invention, the composition may contain the amino acid valine in amounts of 0.1 to 5% (w / v), in particular 0.5 to 3% (w / v), preferably 1 to 2% (w / v), based on the composition.

[0075] The numerous aforementioned amino acids, contained in the specified amounts in the whey proteins, are particularly well absorbed by the body. Furthermore, the specific composition of the whey proteins used according to the invention, especially those based on beta-lactoglobulin, is particularly advantageous and can be used by the body, for example, directly in supplying muscles and bones.

[0076] According to the invention, the composition may also contain tryptophan, preferably in the form of L-tryptophan. Tryptophan is an aromatic amino acid and cannot be produced by the human body. In other words, tryptophan is an essential amino acid and must be obtained through diet.

[0077] As previously explained, a low phosphate content is advantageous according to the invention. Therefore, the composition generally contains less than 1000 ppm, in particular less than 500 ppm, preferably less than 400 ppm, and preferably less than 300 ppm, phosphate, based on the weight of the composition. "ppm" stands for "parts per million," i.e., the number of parts, for example, parts by weight, per million total parts.

[0078] The composition according to the invention is therefore ideally suited as a low-phosphate protein supplement, particularly for patients with renal insufficiency. The composition according to the invention counteracts hyperphosphatemia and resulting diseases, such as secondary hyperparathyroidism.

[0079] Within the scope of the present invention, it is preferred if the composition is particularly low in phosphate.

[0080] Furthermore, within the scope of the present invention, it is preferred if the composition has a weight-related phosphorus-protein quotient (PEQ) in the range of 0.01 to 5, in particular 0.02 to 2, preferably 0.05 to 1, preferably 0.08 to 0.5.

[0081] The phosphorus-protein ratio indicates how many milligrams of phosphorus, calculated as phosphate, the composition contains in relation to the grams of protein it contains. The phosphorus-protein ratio is important for the nutrition of patients with renal insufficiency, particularly dialysis patients, and foods or dietary supplements with a particularly low phosphorus-protein ratio are preferable. The composition according to the invention has an extremely low phosphorus-protein ratio (PEQ) and is therefore ideally suited for meeting the increased protein requirements of patients with chronic renal insufficiency, especially dialysis patients.

[0082] Furthermore, the composition may contain potassium. The amount of potassium in the composition according to the invention can vary widely. However, particularly good results are obtained within the scope of the present invention when the composition contains less than 2000 ppm, in particular less than 1000 ppm, preferably less than 500 ppm, and preferably less than 300 ppm, potassium by weight. The composition according to the invention thus counteracts an elevated potassium level in the blood serum and therefore prevents excessively high potassium levels in the blood, the so-called hyperkalemia.

[0083] It is also possible, within the scope of the present invention, for the composition to contain sodium. As for the amount of sodium in the composition according to the invention, this can also vary widely. However, particularly good results are obtained within the scope of the present invention when the composition contains less than 1,000 ppm, in particular less than 500 ppm, preferably less than 300 ppm, sodium, based on the weight of the composition. The composition according to the invention is thus not only low in phosphate and potassium, but also low in sodium.

[0084] Furthermore, the composition according to the invention is generally low in calories, i.e., it has a low physiological energy value. Within the scope of the present invention, it has proven advantageous if the composition has a physiological energy value of less than 1000 kJ, in particular less than 800 kJ, preferably less than 600 kJ, based on 100 g of the composition. The composition according to the invention is therefore also suitable for diabetics and is specifically designed to meet increased protein requirements without the uncontrolled supply of other nutrients that the patient may not need.

[0085] In general, the composition contains additives and / or flavorings.

[0086] As regards the quantity of excipients and / or flavorings in the composition according to the invention, this can naturally vary over a wide range. However, it has proven advantageous if the composition contains the excipients and / or flavorings in quantities of 0.01 to 15% (w / v), in particular 0.1 to 10% (w / v), preferably 0.2 to 5% (w / v), based on the composition.

[0087] If the composition according to the invention contains excipients and / or flavorings, these are typically selected from sugars, in particular sucrose, glucose and / or fructose, sugar substitutes, sweeteners, acidulants, preservatives, flavorings, colorings and stabilizers, as well as mixtures and combinations thereof. The aforementioned excipients and flavorings are used in particular to make the sensory experience, especially the mouthfeel, consistency and taste of the composition according to the invention, as pleasant as possible for the patient. When excipients and / or flavorings are used within the scope of the present invention, they are typically used only in extremely small quantities.

[0088] According to a preferred embodiment of the present invention, the composition is in the form of an aqueous solution or dispersion, which (a) 20 to 50% (w / v) beta-lactoglobulin, based on composition, (b) 0.01 to 2% (w / v) 3-hydroxy-3-methylbutyric acid, and (c) 0.01 to 15% (w / v) excipients and / or flavorings, in each case based on the composition, exhibits.

[0089] According to a further, equally preferred embodiment of the present invention, the composition according to the invention is in the form of an aqueous solution or dispersion and consists of (a) 20 to 50% (w / v) beta-lactoglobulin, based on composition, (b) 0.01 to 2% (w / v) 3-hydroxy-3-methylbutyric acid, (c) 0.01 to 15% (w / v) excipients and / or flavorings, in each case based on the composition, and (d) Water, the composition (I) less than 300 ppm phosphate and (II) less than 300 ppm potassium, each based on the weight of the composition, contains and the composition has a weight-related phosphorus-protein quotient (PEQ) in the range of 0.01 to 5.

[0090] The composition according to the invention is therefore preferably a highly concentrated liquid protein preparation based on beta-lactoglobulin, which is low in phosphate and potassium and is ideally suited to meet the increased protein requirements of patients with renal insufficiency, in particular dialysis patients.

[0091] As previously stated, the composition according to the invention is typically in the form of a liquid solution or dispersion. The dynamic viscosity of the composition can also vary widely.

[0092] The composition according to the invention is thus a low-viscosity liquid that is easy to dose and, moreover, can be removed from containers easily and almost without residue. This is important, for example, when packaging the composition according to the invention in special dosing forms, since it must be ensured that the amount of composition actually filled into a container can also be dispensed by the consumer or patient.

[0093] A further object of the present invention - according to a second aspect of the present invention - is the composition described above for use in the therapeutic treatment of protein deficiency diseases in patients with renal insufficiency, in particular dialysis patients.

[0094] As previously stated, the composition according to the invention is ideally suited for the treatment of protein deficiency diseases, in particular also as a dietary supplement to meet the increased protein requirements of persons with renal insufficiency, especially dialysis patients.

[0095] In the context of the present invention, therapeutic treatment is understood to mean both curative treatment of diseases or disease symptoms and preventive treatment, i.e., prevention of the outbreak of diseases or disease symptoms.

[0096] A further object of the present invention - according to a third aspect of the present invention - is the composition described above for use in the therapeutic treatment of hyperphosphatemia, particularly in persons with renal insufficiency, for example dialysis patients.

[0097] A further object of the present invention - according to a fourth aspect of the present invention - is the composition according to the invention for use in the therapeutic treatment of secondary hyperparathyroidism, in particular in persons with renal insufficiency, such as dialysis patients.

[0098] Due to the high protein concentration and simultaneously low phosphate content, the composition according to the invention can be used in the prevention and treatment of phosphatemia and the resulting secondary hyperparathyroidism.

[0099] According to a particularly preferred embodiment of the present invention, the composition according to the invention is provided in the form of a single-day dose, particularly for oral administration, for use in therapeutic treatments – especially according to the second to fourth aspects of the present invention. The composition according to the invention is thus preferably provided in the form of a single-day dose, a so-called "shot". This not only saves the patient the time-consuming and error-prone task of mixing a powdered protein concentrate with a liquid, but also prevents incorrect dosages by providing the composition in the form of a single-day dose.

[0100] Regarding the amount of peptides in the single-day dose, this can vary considerably. From a medical perspective, however, it is advantageous if the single-day dose contains whey proteins in an amount of 10 to 30 g, particularly 15 to 25 g, preferably 18 to 22 g, and preferably exactly 20 g, based on the single-day dose. The aforementioned values ​​correspond to the protein gap in patients with chronic renal insufficiency, especially dialysis patients, who should not consume more than 1,000 mg of phosphate per day.

[0101] Furthermore, within the scope of the present invention, it has also proven advantageous if the single-day dose has a volume of 30 to 120 ml, in particular 40 to 100 ml, preferably 50 to 80 ml, and more preferably 60 to 70 ml. The composition according to the invention, in the form of a single-day dose, is thus a highly concentrated liquid protein preparation that does not result in unnecessary and excessive fluid intake for dialysis patients.

[0102] Typically, the single-day dose is also very low in calories; in particular, it has a physiological energy value of less than 600 kJ, especially less than 500 kJ, preferably less than 450 kJ, based on the single-day dose. The single-day dose for therapeutic treatment can therefore be used without problems by diabetics.

[0103] The composition according to the invention is therefore a highly concentrated, liquid, phosphate- and potassium-poor protein concentrate, which is ideally suited for substituting the increased protein requirements of patients with renal insufficiency, in particular dialysis patients.

[0104] The composition according to the invention is based on beta-lactoglobulin, preferably from cow's milk, which on the one hand provides a particularly advantageous, diverse and essential amino acid spectrum for the body and eliminates the need for collagen-containing preparations, making the composition suitable for vegetarians as well.

[0105] The composition according to the invention, in the form of a single daily dose, is precisely adapted to the increased protein requirements of dialysis patients.

[0106] The improved protein absorption and low phosphate load of the composition according to the invention can reduce the mortality of dialysis patients.

[0107] The composition according to the invention is also suitable for diabetics, since it does not contain any additional physiological energy value in the form of carbohydrates.

[0108] The composition according to the invention is provided in the form of a ready-to-use single-day dose, i.e., the mixing of powders, which is usual with protein preparations of the prior art, is eliminated, which carries the risk of incorrect dosages and can no longer be carried out independently by, for example, elderly people.

[0109] The composition according to the invention is particularly easy to use and dose due to its availability in liquid form.

[0110] For further details regarding the composition according to the invention for use in therapeutic treatments, reference can be made to the previous descriptions of the composition according to the invention, which apply accordingly to the composition according to the invention for use in therapeutic treatments.

[0111] Yet another object of the present invention - according to a fifth aspect of the present invention - is the use of a previously described composition as a food supplement.

[0112] In particular, the composition described above can be used to replace the increased protein requirement in cases of renal insufficiency, especially in dialysis patients.

[0113] For further details regarding the use according to the invention, reference may be made to the previous aspects of the invention, which apply accordingly to the use according to the invention.

[0114] A further object of the present invention - according to a sixth aspect of the present invention - is the use of a previously described composition in the therapeutic treatment of protein deficiency diseases in persons with renal insufficiency, in particular dialysis patients.

[0115] For further details on this aspect of the invention, reference may be made to the previous statements on the other aspects of the invention, which apply accordingly to the use according to the invention.

[0116] Yet another object of the present invention - according to a seventh aspect of the present invention - is the use of a previously described composition in the therapeutic treatment of hyperphosphatemia, particularly in persons with renal insufficiency, such as dialysis patients.

[0117] For further details on this aspect of the invention, reference can be made to the explanations of the other aspects of the invention, which apply accordingly to the use according to the invention.

[0118] Finally, a further object of the present invention – according to an eighth aspect of the present invention – is the use of a previously described composition in the therapeutic treatment of secondary hyperparathyroidism, particularly in persons with renal insufficiency, for example dialysis patients.

[0119] As regards the uses according to the invention, it is preferred if the composition is in the form of a single daily dose, especially for oral administration, particularly as a so-called "shot".

[0120] Likewise, particularly good results are obtained within the scope of the present invention if the single daily dose contains the peptides in an amount of 10 to 30 g, in particular 15 to 25 g, preferably 18 to 22 g, preferably 20 g, based on the single daily dose.

[0121] When the composition is used in the form of a single daily dose, the single daily dose has a volume of 30 to 120 ml, in particular 40 to 100 ml, preferably 50 to 80 ml, preferably 60 to 70 ml.

[0122] Furthermore, the composition used in the present invention has an extremely low physiological calorific value and is therefore low in calories. The physiological calorific value of the single daily dose can vary considerably. However, in the present invention, particularly good results are obtained when the physiological calorific value of the single daily dose is less than 600 kJ, in particular less than 500 kJ, and preferably less than 450 kJ.

[0123] For further details concerning the aspects of the invention relating to the uses according to the invention, reference can be made to the previous statements relating to the other aspects of the invention, which apply accordingly to the uses according to the invention.

[0124] The subject matter of the present invention is illustrated below by the exemplary embodiments, which exemplify the subject matter of the present invention without being restrictive in any way. Examples of implementation:

[0125] Low-viscosity dispersions are mixed from water, beta-lactoglobulin from cow's milk, citric and malic acid as acidulants, potassium sorbate and sodium benzoate as preservatives, sucralose and acesulfame K as sweeteners, and flavorings.

[0126] The dispersions are homogeneous and have a stable shelf life of several months. They are packaged in 60 ml portions with a protein content of 20 g, which corresponds to a single daily dose, a so-called "shot".

[0127] The compositions of the single-day doses are given in the tables below. Table 1: Nutritional information per a single daily dose of 60 ml ml per serving 60 Calorific value kJ 348 kcal 82 Fat g < 0,5 hereof: saturated fatty acids 9 < 0,1 carbohydrates g < 0,5 of which sugar g 0 protein g 20 Salt g 0,04 Nutrients: HMB mg 100 Beta-lactoglobulin, of which amino acids: mg 20.000 Alanine mg 1200 Arginine mg 470 Aspartic acid mg 1980 Cysteine mg 510 Glutamic acid mg 3560 Glycine mg 240 Histidine mg 270 Isoleucine mg 1100 Leucin mg 2750 Lysine mg 2070 Methionine mg 580 Phenylalanine mg 630 Proline mg 970 Serine mg 680 Threonine mg 920 Tryptophan mg 370 Tyrosine mg 660 Valin mg 1050 QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] DE 10 2012 110 612 A1

[0022] DE 20 2014 105 602

[0024]

Claims

Composition, in particular for protein substitution in renal insufficiency, characterized in that the composition is in liquid form and contains (a) whey protein in an amount of 15 to 50% (w / v), and (b) 3-hydroxy-3-methylbutyric acid in an amount of 0.01 to 3% (w / v), in each case based on the composition. Composition according to claim 1, characterized in that the composition comprises whey protein, whey protein isolate, whey protein concentrate and / or whey protein hydrolysate, preferably whey protein isolate. Composition according to claim 1 or 2, characterized in that the composition contains whey protein isolate as whey protein and that the whey protein isolate is beta-lactoglobulin. Composition according to one of the preceding claims, characterized in that the composition contains whey protein, in particular whey protein isolate, in an amount of 20 to 45% (w / v), in particular 25 to 40% (w / v), preferably 30 to 35% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains 3-hydroxy-3-methylbutyric acid in an amount of 0.05 to 2% (w / v), in particular 0.1 to 1% (w / v), preferably 0.12 to 0.18% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains proteins, preferably in the form of whey protein, in an amount of 15 to 50% (w / v), in particular 20 to 40% (w / v), preferably 25 to 35% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid alanine in amounts of 0.1 to 5.0% (w / v), in particular 0.5 to 4.9% (w / v), preferably 1 to 2.5% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid arginine in amounts of 0.01 to 3% (w / v), in particular 0.1 to 2% (w / v), preferably 0.5 to 1.3% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid aspartic acid in amounts of 0.5 to 15% (w / v), in particular 1 to 10% (w / v), preferably 2 to 6% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid cysteine ​​in amounts of 0.01 to 4% (w / v), in particular 0.1 to 2% (w / v), preferably 0.5 to 1.5% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid glutamic acid in amounts of 1 to 15% (w / v), in particular 2 to 10% (w / v), preferably 3 to 8% (w / v), preferably 4 to 6% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid glycine in amounts of 0.01 to 3% (w / v), in particular 0.05 to 2% (w / v), preferably 0.1 to 1% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid histidine in amounts of 0.01 to 3% (w / v), in particular 0.05 to 2% (w / v), preferably 0.1 to 1% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid isoleucine in amounts of 0.5 to 8% (w / v), in particular 1 to 5% (w / v), preferably 1.5 to 2% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid leucine in amounts of 1 to 15% (w / v), in particular 2 to 10% (w / v), preferably 3 to 6% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid lysine in amounts of 0.5 to 12% (w / v), in particular 1 to 10% (w / v), preferably 2 to 5% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid methionine in amounts of 0.1 to 3% (w / v), in particular 0.5 to 2% (w / v), preferably 0.8 to 1.3% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid phenylalanine in amounts of 0.05 to 5% (w / v), in particular 0.1 to 3% (w / v), preferably 0.5 to 1.5% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid proline in amounts of 0.05 to 6% (w / v), in particular 0.1 to 5% (w / v), preferably 1 to 3% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid serine in amounts of 0.05 to 5% (w / v), in particular 0.1 to 3% (w / v), preferably 0.5 to 1.5% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid threonine in amounts of 0.05 to 6% (w / v), in particular 0.1 to 5% (w / v), preferably 1 to 3% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid tryptophan in amounts of 0.01 to 3% (w / v), in particular 0.1 to 2% (w / v), preferably 0.5 to 1.3% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid tyrosine in amounts of 0.05 to 5% (w / v), in particular 0.1 to 3% (w / v), preferably 0.5 to 1.5% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains the amino acid valine in amounts of 0.1 to 5% (w / v), in particular 0.5 to 3% (w / v), preferably 1 to 2% (w / v), based on the composition. Composition according to one of the preceding claims, characterized in that the composition contains less than 1000 ppm, in particular less than 500 ppm, preferably less than 400 ppm, preferably less than 300 ppm, phosphate, based on the weight of the composition, in particular wherein the composition is low in phosphate. Composition according to one of the preceding claims, characterized in that the composition has a weight-related phosphorus-protein quotient (PEQ) in the range of 0.01 to 5, in particular 0.02 to 2, preferably 0.05 to 1, preferably 0.08 to 0.

5. A composition according to any of the preceding claims, characterized in that the composition contains less than 2000 ppm, in particular less than 1000 ppm, preferably less than 500 ppm, preferably less than 300 ppm, potassium, based on the weight of the composition; and / or that the composition contains less than 1000 ppm, in particular less than 500 ppm, preferably less than 300 ppm, sodium, based on the weight of the composition. Composition according to one of the preceding claims, characterized in that the composition has a physiological calorific value of less than 1000 kJ, in particular less than 800 kJ, preferably less than 600 kJ, based on 100 g of composition. A composition according to any of the preceding claims, characterized in that the composition contains auxiliary and / or flavoring substances, in particular wherein the composition contains the auxiliary and / or flavoring substances in amounts of 0.01 to 15% (w / v), in particular 0.1 to 10% (w / v), preferably 0.2 to 5% (w / v), based on the composition, and / or in particular wherein the auxiliary and / or flavoring substances are selected from sugars, in particular sucrose, glucose and / or fructose, sugar substitutes, sweeteners, acidulants, preservatives, flavorings, colorings and stabilizers as well as mixtures and combinations thereof. A composition according to any one of the preceding claims in the form of an aqueous solution or dispersion, comprising (a) 20 to 50% (w / v) beta-lactoglobulin, based on the composition, (b) 0.01 to 2% (w / v) 3-hydroxy-3-methylbutyric acid, (c) 0.01 to 15% (w / v) excipients and / or flavorings, each based on the composition, and (d) water, wherein the composition contains (I) less than 300 ppm phosphate and (II) less than 300 ppm potassium, each based on the composition, and wherein the composition has a weight-based phosphorus-to-protein ratio (PEQ) in the range of 0.01 to 5. Composition according to any of the preceding claims for use in the therapeutic treatment of protein deficiency diseases in persons with renal insufficiency, in particular dialysis patients. Composition according to any of the preceding claims for use in the therapeutic treatment of hyperphosphatemia, particularly in persons with renal insufficiency. Composition according to any of the preceding claims for use in the therapeutic treatment of secondary hyperparathyroidism, particularly in persons with renal insufficiency. Use of a composition according to any one of claims 1 to 31 as a food supplement.