Chewable and / or suckable mass based on a hydrocolloid gel

Abstract

A chewable and / or suckable mass based on a hydrocolloid gel contains at least one source of magnesium ions and at least one beneficial active ingredient. The beneficial active ingredient may include at least one form of vitamin D and / or at least one chromium salt. Such masses are suitable for use in the treatment of people with diabetes mellitus.

Description

[0001] The present invention relates to a chewable and / or suckable mass based on a hydrocolloid gel containing at least one magnesium ion source and at least one beneficial active ingredient. The invention further relates to the mass for use in the treatment of an existing or impending deficiency of the beneficial active ingredient.

[0002] Vitamin D is the only vitamin that the human body can produce itself, namely with the help of sunlight. With sufficient sun exposure, the body can produce the majority of the required vitamin (80 to 90%). Diet contributes only about 10 to 20% to vitamin D intake. However, in winter, it is not possible to obtain sufficient sunlight in every region. In Central Europe, for example, far too little of the necessary UVB radiation reaches the earth during the cold season (October to March), which is why vitamin D deficiency is widespread.

[0003] Strictly speaking, vitamin D isn't a true vitamin. By definition, vitamins are essential organic compounds that the body must regularly obtain through food because it cannot produce them itself, or not in sufficient quantities. However, this doesn't apply to vitamin D. Strictly speaking, the term "hormone precursor" (prohormone) would be more accurate for vitamin D, since the body converts it into a hormone called calcitriol. Calcitriol is the biologically active form of vitamin D.

[0004] The term vitamin D encompasses several fat-soluble compounds. One of these is vitamin D3 (also called cholecalciferol), which is converted in the liver and kidneys into the active hormone calcitriol. The body can also convert vitamin D3 into a storage form called calcifediol (also known as 25-hydroxy vitamin D or 25-OH vitamin D). Another form is vitamin D2 (ergocalciferol), which is converted in the body into the more active form, vitamin D3.

[0005] Diabetics, whether they have type 1 or type 2 diabetes, are more likely to suffer from a vitamin D deficiency than healthy people, so vitamin D supplementation can be helpful for them (Dong, J. et al., Vitamin D Intake and Risk of Type 1 Diabetes: A Meta-Analysis of Observational Studies, Nutrients 2013, 5, 3551-3562).

[0006] In the case of type 1 diabetes, an autoimmune disease, there is another correlation: people who consumed a lot of vitamin D in their first year of life are less likely to develop type 1 diabetes later in life. Similar correlations were found when mothers had high vitamin D levels during pregnancy. Their children were subsequently less at risk of later receiving a type 1 diabetes diagnosis (Hyppönen, E. et al., Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study, The Lancet 2001, 3, 1500-1503; Sørensen, I. et al. Maternal Serum Levels of 25-Hydroxy-Vitamin D During Pregnancy and Risk of Type 1 Diabetes in the Offspring, Diabetes 2012, 61, 175-178; Aljabri, K. et al. Glycemic changes after vitamin D supplementation in patients with type 1 diabetes mellitus and vitamin D deficiency, Annals of Saudi Medicine 2010, 30, 454-458).

[0007] The largest study to date on vitamin D for diabetes prevention included 2,423 men and women (average age 60 years) with prediabetes and obesity. They received 4,000 IU / day of vitamin D3 or a placebo for two years. Most participants (78%) had sufficient vitamin D levels at the start of the study. Vitamin D did not statistically significantly prevent the development of diabetes compared to placebo. However, a follow-up analysis showed that the incidence of diabetes was 62% lower when participants with low baseline vitamin D levels took the vitamin D supplement (Pittas A. et al. Vitamin D supplementation and prevention of type 2 diabetes, N Engl J Med 2019, 381, 520-530; Li X. et al., The effect of vitamin D supplementation on glycemic control in type 2 diabetes patients: A systematic review and meta-analysis, Nutrients 2018, 10, 375).

[0008] Another study investigated the effect of vitamin D on HbA1c levels, the long-term blood sugar level. HbA1c is a value that rises the worse blood sugar control has been in recent weeks. A low HbA1c level is therefore an indicator of long-term stable blood sugar levels. The study ran for two years. During this time, the participants, who had type 2 diabetes, were able to raise their vitamin D levels from 25 ng / ml to 34 ng / ml, and their HbA1c levels decreased significantly (Green, R. et al. Maintenance of long-term adequate levels of vitamin d lowers HbA1c in African American patients with type 2 diabetes. Ethn Dis, 2014, 24, 335-341).

[0009] However, a vitamin D deficiency not only worsens the diabetes itself, but also increases the incidence of typical diabetes-related complications. These include, in particular, vascular diseases, i.e., damage to the blood vessels due to the frequently elevated blood sugar levels in diabetes.

[0010] However, if the blood vessels are damaged, circulatory disorders occur in the affected organs. This can result in damage to the kidneys (nephropathy), the nerves (neuropathy or polyneuropathy), and the eyes (retinopathy).

[0011] Exercise can deplete the body's magnesium stores, which can impair energy metabolism, oxygen uptake, and electrolyte balance (Siegler, J. et al., Pre-exercise alkalosis and acid-base recovery. Int J Sports Med. 2008, 29, 545-551).

[0012] Furthermore, magnesium is essential for the smooth functioning of muscle metabolism, as neuromuscular coordination and all enzyme reactions in the muscle require a sufficient concentration of magnesium ions. A magnesium deficiency in athletes manifests itself particularly in the form of muscle cramps and stiffness, as well as accelerated muscle fatigue (Kasel, U., Rempfer, N., pH-dependent solubility. Magnesium compounds in comparison. Biogena inside Mineral Show 2013).

[0013] The highly soluble organic magnesium compounds (e.g., citrate, gluconate, malate, lactate) are generally more bioavailable than the inorganic compounds (e.g., carbonate, oxide, sulfate). Magnesium orotate is only approved for use in pharmaceuticals. Soluble organic compounds, especially chelates with amino acids, exhibit high bioavailability.

[0014] A 2011 analysis of studies investigating the relationship between adequate magnesium intake and the risk of type 2 diabetes included 13 studies with a total of 536,318 participants. The researchers found an association between magnesium intake and the risk of type 2 diabetes. This association reached statistical significance in overweight individuals (body mass index 25 or higher), but not in normal-weight individuals (BMI below 25, Pittas A. et al. Vitamin D supplementation and prevention of type 2 diabetes, N Engl J Med 2019, 381, 520-530; Li X. et al., The effect of vitamin D supplementation on glycemic control in type 2 diabetes patients: A systematic review and meta-analysis, Nutrients 2018, 10, 375).

[0015] Vitamin D supports the bioavailability of magnesium.

[0016] The ESAF has permitted the health claim “contributes to normal energy metabolism” for magnesium (EFSA Journal 2009; 7(9):1216).

[0017] Chromium is also used therapeutically in diabetes mellitus, as diabetics excrete increased amounts of chromium (chromuria), which manifests as lower plasma levels. For example, the levels of chromium excreted in the urine of diabetics are up to 100% higher than those of healthy individuals, while at the same time plasma levels are reduced by 33% (Morris, B. et al., Chromium Homeostasis in Patients with Type II (NIDDM) Diabetes, Journal of Trace Elements in Medicine and Biology 1999, 13, 57-61).

[0018] Chromium is an active component of the glucose tolerance factor, which can only be formed in the presence of sufficient trivalent chromium. The glucose tolerance factor regulates the binding of insulin to specific receptors on cell membranes. This improves glucose utilization and optimizes insulin action (Gröber U. 2002, Orthomolecular Medicine. A Guide for Pharmacists and Physicians). Chromium can also interact directly with the receptors. This occurs by stimulating a phosphorylation reaction similar to that triggered by insulin. Chromium, zinc, and selenium are therefore also referred to as insulin-mimetic agents (Miranda, E. et al., Effect of Chromium and Zinc on Insulin Signaling in Skeletal Muscle Cells, Biol Trace Elem Res. 2004, 101, 19-36).

[0019] The EFSA has approved the following health claims for chromium, which are important for diabetics: “contributes to normal macronutrient metabolism and to the maintenance of normal blood glucose levels” (EFSA Journal 2010; 8(10):1732).

[0020] These studies show that administering the micronutrients vitamin D in combination with magnesium and chromium can be beneficial. Furthermore, vitamin D is absorbed in the oral cavity and, like chromium, is very poorly water-soluble. A formulation should be developed that provides sufficient amounts of these micronutrients with good bioavailability in a chewable form.

[0021] A chewing gum base containing one or more of the vitamins A, D, E, and K is described in utility model DE 20 2004 010 021 U1. This chewing gum base is produced by adding the vitamins A, D, E, and K and / or one of their derivatives to a heated solubilizer, such as polysorbate 80 or polysorbate 20, while stirring, and continuing to stir until a homogeneous, and in particular clear, composition is obtained. The homogeneous composition is then incorporated into a thickening agent.

[0022] EP 1 338 271 A1 describes the production of a vitamin solubilisate in which a fat-soluble vitamin (α-tocopherol, retinol, β-carotene) is mixed with polysorbate 20 or polysorbate 80 and stirred until a clear solubilisate is formed.

[0023] The use of emulsifiers, such as polysorbates, in the manufacture of oral formulations generally has the physiological disadvantage that such compounds, especially with repeated use, can negatively affect the digestive system and lead to diarrhea. Such side effects are particularly undesirable for diabetics. The administration of oil-containing preparations of solubilized fat-soluble vitamins, such as those commonly found in oil-filled soft gelatin capsules, can also be very detrimental to patients with impaired digestive systems and should therefore be avoided. These preparations often do not contain minerals because they do not distribute or dissolve homogeneously.

[0024] The liquefaction of hydrocolloids, particularly those based on gelatin, at higher temperatures is problematic. Gelatin swells in water and dissolves upon heating at around 50 °C. It is a hydrocolloid in which the gel formed (during cooling) liquefies again upon heating. This gel / sol transition is thermoreversible, but causes problems with physical stability because the structure can deteriorate.

[0025] The present invention was therefore based on the objective of providing a stable hydrocolloid form, even at higher temperatures, in particular for use in the treatment of a person with diabetes mellitus.

[0026] This task was solved by a chewable and / or suckable mass based on a hydrocolloid gel, containing - at least one source of magnesium ions, and - at least one beneficial active ingredient.

[0027] Surprisingly, it was found that the inventive magnesium ion-containing micronutrient formulation, in the form of a chewable and / or suckable mass, yields stable hydrocolloid forms even at elevated temperatures. Without being bound to theory, it is assumed that magnesium, as a multivalent ion, is suitable for crosslinking hydrocolloids, which presumably results in the gel / sol transition in a resulting hydrocolloid form being thermoreversible, i.e., irreversible. This advantageously overcomes the aforementioned problems of physical and thermal stability and prevents the hydrocolloid form from dissolving. Furthermore, magnesium is not only harmless in dosage forms such as chewable and / or suckable masses, but also advantageously serves as a micronutrient.

[0028] The term "beneficial agent" as used here refers to any compound or material that has a desired physiological effect, such as a therapeutic effect, or whose insufficient supply can lead to a deficiency or imminent threatens to occur. Beneficial agents generally include biomaterials such as pharmaceuticals, vitamins, nutrients, and dietary supplements.

[0029] The beneficial active ingredient can - at least one form of vitamin D, and / or - contain at least one chromium salt, preferably at least one chromium(III) salt.

[0030] The mass, in relation to the total mass of the chewable and / or suckable mass, should expediently contain - at least 1 wt.%, preferably at least 2 wt.%, in particular at least 4 wt.%, e.g. 1 to 8 wt.%, 2 to 7 wt.% of magnesium ion source(s), calculated as magnesium, - at least 0.0001 wt.%, preferably at least 0.0003 wt.%, in particular at least 0.001 wt.%, in particular at least 0.005 wt.%, e.g. 0.0003 to 0.050 wt.%, 0.001 to 0.040 wt.% or 0.005 to 0.040 wt.%, of form(s) of vitamin D, - at least 0.0001 wt.%, preferably at least 0.0005 wt.%, in particular at least 0.001 wt.%, e.g. 0.0001 to 0.200 wt.%, e.g. 0.0005 to 0.005 wt.% of chromium salt(s), calculated as chromium.

[0031] In one embodiment, the magnesium ion source is a magnesium salt.

[0032] The magnesium salt is preferably selected from organic magnesium salts, such as magnesium citrate, magnesium gluconate, magnesium malate, magnesium lactate, magnesium orotate, or inorganic magnesium salts, such as magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium sulfate. Soluble organic compounds, especially chelates with magnesium amino acids, are also suitable.

[0033] The magnesium salt is preferably selected from magnesium oxide, magnesium hydroxide, magnesium citrate, and mixtures thereof. Magnesium hydroxide, magnesium citrate, and mixtures thereof are particularly preferred.

[0034] Particularly preferred are mixtures of an organic magnesium salt and an inorganic magnesium salt, e.g. a mixture of magnesium citrate and magnesium hydroxide.

[0035] The hydrocolloid contained in the mass according to the invention is selected from water-soluble and water-swellable gel-forming polysaccharides and proteins. These include in particular: - Pectins (galacturonic acid-rich polysaccharides), such as homoglacturonans, substituted galacturonans (with terminal D-xylose or D-apiose residues), rhamnogalacturonan I pectins, rhamnogalacturonan II pectins, and especially pectins with a number-mean molecular weight in the range of 60 to 130,000; - Gum arabic; - Galactomannans, such as guar gum, carob (from carob tree), konjac (from devil's tongue); - Agar; - Carrageenan, such as K-, I- and λ-carrageenan; - Alginates; - Alginic acids; - Gelatin such as acid-treated gelatin (low cross-linked collagen) or base-treated gelatin (high cross-linked collagen), which can be obtained from cattle, pigs or fish, for example, and in particular gelatin with a Bloom value (gel strength) of 30 to 300 and / or a number-average molecular weight of 15,000 to 25,000; - Xanthan gum, especially as a mixture with locust bean gum; - Tragacanth; and - Mixtures of these hydrocolloids.

[0036] Pectins and gelatins are preferred among these.

[0037] Typically, the water content of hydrocolloid gel is 1 to 35 wt%. The water content of hydrocolloid gel can be 5 to 30 wt%, e.g., 10 to 20 wt%.

[0038] Preferably, the hydrocolloid gel is essentially free of emulsifiers. "Essentially free" means that, based on the total mass of fat-soluble vitamins, it contains no more than 100% by weight, in particular no more than 50% by weight, e.g., no more than 20% by weight or no more than 10% by weight, and ideally no emulsifier at all. This reduces or completely avoids undesirable side effects on the patient's digestive system caused by the emulsifier (such as diarrhea).

[0039] The term "emulsifier" refers to surfactants, and in particular polyoxyethylene sorbitan fatty acid esters, with an HLB value (according to Griffin) in the range of 9 to 18 and especially in the range of 12 to 17, such as polysorbate 20 (E432), polysorbate 40 (E434), polysorbate 60 (E435), polysorbate 65 (E436) and polysorbate 80 (E433).

[0040] The composition according to the invention can contain at least one form of vitamin D as a beneficial active ingredient. The term "(form of) vitamin D" refers to several chemical compounds, such as vitamin D3 (cholecalciferol, calciferol), vitamin D2 (calciferol, ergocalciferol), and vitamin D4 (22,23-dihydroergocalciferol, saturated D2). The term "form of vitamin D" also includes provitamins. In particular, "provitamin D" refers to provitamin D2 (ergosterol) and provitamin D3 (7-dehydrocholesterol).

[0041] In the embodiment mentioned above, the form of vitamin D is in particular vitamin D3.

[0042] If present, the form(s) of vitamin D, and, if present, other vitamins and minerals, are present in the hydrocolloid gel in non-emulsifier-soluble form, i.e., they have not been made water-soluble by pretreatment with emulsifiers. The vitamins can be used to produce the mass according to the invention in substance, e.g., in crystalline or oily form, or in pre-dispersed or redispersible powder form. Although the vitamins and minerals are present in non-emulsifier-soluble form, it has been found that the vitamins and minerals contained in the mass according to the invention are well absorbed. Presumably, the hydrocolloid gel matrix, in addition to masking the taste, stabilizes an amorphous dispersed state and enables good solubilization and absorption.

[0043] In one embodiment, the chewable and / or suckable mass contains a high amount of vitamin D and / or provitamin D. This allows 100% or more of the recommended daily allowance of vitamin D and chromium to be administered with a patient-acceptable amount (e.g., 3 g of the mass) (see, e.g., EU RDA ("Recommended Daily Allowance") according to Directive 2008 / 100 / EC or Nutrient Reference Values: Reference intake of vitamins and minerals for adults).

[0044] The aforementioned (pro)vitamins are nonpolar molecules that are very soluble in lipids and can be incorporated into the cells of the intestinal mucosa in chylomicrons in a similar way to cholesterol.

[0045] In general, at least 50 wt.%, preferably at least 60 wt.%, in particular at least 70 wt.%, in particular at least 80 wt.%, in particular at least 90 wt.% and particularly preferably 100 wt.% of the total amount of the at least one form of vitamin D, and, if present, other vitamins and minerals, are in non-crystalline (amorphous) form.

[0046] Investigations to determine crystallinity can be carried out using wide-angle X-ray diffraction (WAXS) or differential scanning calorimetry (DSC). Light microscopy is also particularly suitable.

[0047] Crucial for the bioavailability of the vitamins is the solubility behavior of the composition according to the invention. It is advantageous that a considerable proportion (up to 100%) of the fat-soluble vitamins in the composition are present in an amorphous, dissolved, or semi-crystalline state. Surprisingly, it has been shown that the fat-soluble vitamins and provitamins can be released from the composition according to the invention in aqueous media (such as 0.1 N hydrochloric acid) and do not spontaneously precipitate, even in the absence of emulsifiers. This allows vitamin D to be readily absorbed by the body.

[0048] The mass according to the invention can contain at least one chromium salt as a useful active ingredient.

[0049] The chromium salt is expediently selected from organic chromium salts, such as chromium(III) lactate, chromium(III) picolinate, or inorganic chromium salts, such as chromium(III) chloride, chromium(III) sulfate, chromium(III) nitrate.

[0050] In one embodiment, the chromium salt is chromium(III) chloride.

[0051] If present, the vitamins, provitamins, and minerals in the hydrocolloid gel are typically homogeneously distributed (dispersed). Preferably, the at least 50% by weight of vitamins and, if present, provitamins and minerals are present in the hydrocolloid gel in the form of a solid solution (i.e., molecularly dispersed). The term "solid solutions" is familiar to those skilled in the art; see Chiou and Riegelman, J. Pharm. Sci. 1971, 60, 1281-1302. Surprisingly, such a distribution of the fat-soluble (pro)vitamins and minerals is also possible in the presence of water.

[0052] The term "minerals" here refers in particular to salts of magnesium and chromium and also includes other physiologically important salts, such as zinc salts, which may be selected from zinc sulfate and zinc oxide.

[0053] In addition to the aforementioned vitamins and / or provitamins, the chewable and / or suckable mass according to the invention can contain further vitamins and / or provitamins, e.g., vitamins and / or provitamins A, E, and / or K. Furthermore, the chewable and / or suckable mass can contain other substances with biological activity, such as carotenoids (lycopene, lutein, zeaxanthin), coenzymes (e.g., coenzyme Q10), α-lipoic acid, L-carnitine, water-soluble, optionally solubilized vitamins (e.g., B vitamins such as vitamin B6 and vitamin B12, as well as folic acid), fatty acids, amino acids (e.g., L-tryptophan), cofactors (e.g., zinc), phytosterols, (naturally occurring) polyphenols, flavonoids, flavones, antioxidants (e.g., vitamin C), and aminosulfonic acids (e.g., taurine). In the mass according to the invention, vitamin C is preferably used as an antioxidant and zinc is preferably used as a cofactor.

[0054] The mass may therefore also include vitamin C. Vitamin C is preferably used only in a low dose as an antioxidant for the fat-soluble vitamins. For example, the proportion of vitamin C in the chewable and / or suckable mass is up to 6.0 wt.%, preferably 0.001 to 6.0 wt.%, in particular 0.01 to 4.5 wt.%, preferably 0.02 to 4.0 wt.%, e.g. 0.03 to 3.0 wt.%, based on the total mass of the hydrocolloid gel.

[0055] The chewable and / or suckable mass may contain one or more sweeteners, preferably sweeteners that do not affect blood sugar levels. These include sugars such as D-galactose, sugar substitutes such as sorbitol, mannitol, xylitol, maltitol, or artificial sweeteners such as saccharin, sodium cyclamate, acesulfame K, aspartame, steviol glycosides.

[0056] Preferred are D-galactose ((2R,3S,4S,5R,6)-pentahydroxyhexanal) and steviol glycosides such as stevoside (1-O-[(5β,8α,9β, 10α, 13α)-13-{[2-O-(β-D-Glucopyranosyl)-β-D-glucopyranosyl]oxy}-18-oxokaur-16-en-18-yl]-β-D-glucopyranose.

[0057] Other galenic excipients such as humectants, binders, disintegrants, flavorings, colorants, wetting agents, or pH-influencing additives (see Sucker et al., Pharmaceutical Technology, Thieme-Verlag, Stuttgart 1978) may also be contained in the chewable and / or suckable mass.

[0058] In general, humectants serve to prevent drying out by binding water or attracting moisture from the air during storage. Humectants can be selected from polyols and sugar alcohols, such as glycerin, sorbitol, xylitol, and mixtures thereof.

[0059] Polyols can also control viscosity, e.g. lower it, and support the solubilization of beneficial active ingredients.

[0060] Advantageously, the composition of the mass according to the invention is tailored to the needs of the patients. That is, it advantageously contains a sufficient concentration of the beneficial active ingredient(s) required by the patient, e.g. fat-soluble vitamin D, magnesium and chromium, and a relatively small proportion of other substances that could potentially impair the patients' digestive system.

[0061] The mass according to the invention preferably contains no antioxidants or preservatives selected from the classes of butylhydroxytoluenes, butylhydroxyanisoles, lecithin, ethoxyquin, methylparaben, propylparaben, sorbic acid, sodium benzoate and ascorbyl palmitate.

[0062] The mass according to the invention is preferably vegetarian and / or kosher and / or halal and / or allergen-free and / or gluten-free and / or free of agents that cause BSE (Bovine spongiform encephalopathy) and other forms of TSE (Transmissible spongiform encephalopathy).

[0063] Furthermore, the invention relates to the chewable and / or suckable mass described above for use in the treatment of an existing or imminent deficiency of a beneficial active ingredient, in particular an existing or imminent vitamin deficiency.

[0064] In particular, the mass described above is a mass for use in the treatment of an existing or imminent deficiency in a person with diabetes mellitus.

[0065] In particular, the mass described above is a mass for use in the treatment of an existing or impending deficiency in a person with autoimmune diseases such as celiac disease.

[0066] The vitamin deficiency can affect one or more vitamins, which are contained in the mass as vitamins or in the form of corresponding provitamins and minerals, e.g., form(s) of vitamin D and / or vitamin C. A preferred embodiment relates to the chewable and / or suckable mass for use in the treatment of an existing or impending vitamin D deficiency. Such deficiencies are known, for example, in autoimmune diseases such as type 1 diabetes.

[0067] The chewable and / or suckable mass according to the invention can be generally used in the treatment of patients with maldigestion and / or malabsorption. In particular, the mass can be used in the treatment of patients with age-related functional malabsorption of fat-soluble compounds, e.g., due to impaired secretion of bile or pancreatic enzymes, as well as in patients suffering from diseases and conditions that affect the small intestine. Such diseases and conditions include, among others, Crohn's disease, ulcerative colitis, cystic fibrosis, cholestasis syndrome, celiac disease (e.g., as a consequence of type 1 diabetes), celiac sprue, liver cirrhosis, alcoholism, eating disorders, small bowel tumors, irritable bowel syndrome, short bowel syndrome, and chronic inflammatory bowel diseases.

[0068] Furthermore, the mass according to the invention can be used post-operatively after procedures on the gastrointestinal tract.

[0069] The composition according to the invention can be administered as a molded pellet, which the patient either sucks or bites / chews and then swallows. This makes the composition particularly suitable for children and patients who cannot or do not want to swallow ordinary tablets. Since the pellets do not have to be swallowed whole, they can be administered without water or any other beverage.

[0070] Furthermore, the size of the molded bodies is important. For easy administration to young patients (children), the molded bodies made of the inventive material are expediently no longer than 2.5 cm (length), no wider than 1.5 cm (width) and no higher than 1.5 cm (height).

[0071] Preferred dosage forms of the chewable and / or suckable mass according to the invention are solid candies, chewing gums, pastilles or drops and in particular chewable gum masses (chewing candies, fruit gums).

[0072] Drops made from the composition according to the invention can be produced, for example, by the rotoforming process. Furthermore, the composition according to the invention can be produced by the droplet method, in which a solution of the components of the composition emerges from nozzles that are vibrated by ultrasound. Such methods are known (see, e.g., WO 2016 / 087276 A1; and Glöckner (ed.), Hobein and Lutz (authors), “Microencapsulation”, Aulis Verlag, 1989).

[0073] Furthermore, the mass according to the invention can, for example, also be produced by a batch process in the melt and poured into deep-drawn blister films for shaping.

[0074] The present invention will be explained in more detail with reference to the following examples. Examples

[0075] A typical composition for the mass according to the invention is given in Table 1. Table 1. ingredient m [mg] m [wt.%] Vitamin D3 0,44 0,03 Magnesium hydrogen citrate pentahydrate 32,50 2,17 Magnesium hydroxide 100,00 6,67 Chromium(III) chloride hexahydrate 10,00 0,67 Vitamin C 40,00 2,67 D-Galactose 100,00 6,67 Water 50,00 3,33 beef gelatin 225,76 15,05 Steviol glycosides 2,50 0,17 Orange oil 14,00 0,93 Lemon oil 4,00 0,27 Glycerin 870,80 58,05 MCT-Öl [1] 50,00 3,33 Σ 1500,00 100 [1] MCT = medium-chain triglycerides from palm and coconut oil Example 1: Production of a chewable mass

[0076] Chewable-looking chewable granules with the composition specified in Table 1 were produced. First, 30 g of porcine gelatin A was mixed with 50 g of water and allowed to swell at room temperature for 15 minutes. Glycerol and galactose were mixed, added to the gelatin, and heated to approximately 60°C. The mixture was then stirred for another 30 minutes. Next, the vitamin and salts were added, and the mixture was stirred at a temperature of 45–50°C. After the solid components had dissolved, the flavoring component was added, and the mixture was poured into molds. The granules hardened within approximately 2 hours. After removal from the molds, the granules were treated with an oiling agent. The resulting granules weighed approximately 2 g each. Example 2: Physical analysis of the chewable mass

[0077] The chewable mass produced in Example 1 was cooled in liquid nitrogen for 2 minutes and then immediately ground into a powder in a vibrating mill (1 minute, 30 Hz). After thawing, the powder became very sticky within minutes. The powder was examined using transmitted light microscopy at 100x magnification (Leica DMLM microscope with polarizing filter and analyzer). No crystalline components were observed in the powder. Example 3: Solubility of the chewable mass

[0078] A powder obtained according to Example 2 from the chewable mass prepared according to Example 1 was suspended in 0.1 M hydrochloric acid (1 g of powder per 100 ml of 0.1 M hydrochloric acid) and stirred for three hours. The powder dissolved completely. Example 4: Chemical analysis of the chewable mass

[0079] The vitamin D content of molded pieces of the chewable mass produced in Example 1 was determined using HPLC / UV (method: DIN EN 12823-2). A duplicate determination was performed, yielding a mean value of 0.415 mg vitamin D per molded piece (theoretical value: 0.440 mg vitamin D per molded piece). Vitamin D was chosen as the indicator vitamin for determining content and stability. After one month of storage of the chewable mass at 25°C, no degradation of vitamin D was observed. Example 5: Measurement of long-term blood glucose, triglyceride and magnesium levels in a type 1 patient

[0080] The chewable mass produced in Example 1 was administered to a male patient with type 1 diabetes at a dose of two chewable portions per day for one month. Before the first ingestion (day 0), both the long-term blood glucose level and the triglyceride level were determined.

[0081] The long-term blood glucose level was determined from whole blood using a Eurolyser Cube-s device (Eurolyser Diagnostics). The triglyceride level was determined using a test kit Assay Kit ab65336 (abcam) by colorimetric analysis (570 nm). Triglyceride levels were also determined from whole blood by mass spectrometry. Measurements were repeated after 28 days (day 28). The results are shown in Table 2. Table 2. Day 0 Day 28 HbA1c (normal value < 5.7%) 8,3% 8,0% Triglycerides (normal value < 2.3 mmol / L) 2.89 mmol / L 1.28 mmol / L Magnesium (normal value 0.66 - 1.07 mmol / L) n.b. [1] 0.82 mmol / L [1] nb = not determined

[0082] The results show an improvement in long-term blood sugar levels and a significant reduction in triglycerides. 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 20 2004 010 021 U1

[0021] EP 1 338 271 A1

[0022] WO 2016 / 087276 A1

[0072] Cited non-patent literature

[0000] Hyppönen, E. et al., Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study, The Lancet 2001, 3, 1500-1503; Sørensen, I. et al. Maternal Serum Levels of 25-Hydroxy-Vitamin D During Pregnancy and Risk of Type 1 Diabetes in the Offspring, Diabetes 2012, 61, 175-178

[0006] Aljabri, K. et al. Glycemic changes after vitamin D supplementation in patients with type 1 diabetes mellitus and vitamin D deficiency, Annals of Saudi Medicine 2010, 30, 454-458

[0006] N Engl J Med 2019, 381, 520-530; Li X. et al., The effect of vitamin D supplementation on glycemic control in type 2 diabetes patients: A systematic review and meta-analysis, Nutrients 2018, 10, 375

[0007] Green, R. et al. Maintenance of long-term adequate levels of vitamin d lowers HbA1c in African American patients with type 2 diabetes. Ethn Dis, 2014, 24, 335-341

[0008] Siegler, J. et al., Pre-exercise alkalosis and acid-base recovery. Int J Sports Med. 2008, 29, 545-551

[0011] BMI unter 25, Pittas A. et al. Vitamin D supplementation and prevention of type 2 diabetes, N Engl J Med 2019, 381, 520-530; Li X. et al., The effect of vitamin D supplementation on glycemic control in type 2 diabetes patients: A systematic review and meta-analysis, Nutrients 2018, 10, 375

[0014] Morris, B. et al., Chromium Homeostasis in Patients with Type II (NIDDM) Diabetes, Journal of Trace Elements in Medicine and Biology 1999, 13, 57-61

[0017] Miranda, E. et al., Effect of Chromium and Zinc on Insulin Signaling in Skeletal Muscle Cells, Biol Trace Elem Res. 2004, 101,19-36

[0018] Chiou und Riegelman, J. Pharm. Sci. 1971, 60, 1281-1302

[0051] DIN EN 12823-2

[0079]

Claims

[1] Chewable and / or suckable mass based on a hydrocolloid gel, containing - at least one source of magnesium ions, and - at least one beneficial active ingredient. [2] Mass according to claim 1, wherein the beneficial active ingredient - at least one form of vitamin D, and / or - contains at least one chromium salt. [3] Mass according to claim 1 or 2, comprising, based on the total mass of the chewable and / or suckable mass, - at least 1 wt% of magnesium ion source(s), calculated as magnesium, - at least 0.0001% by weight of form(s) of vitamin D, - at least 0.0001 wt% of chromium salt(s), calculated as chromium. [4] Mass according to any of the preceding claims, wherein the magnesium ion source is a magnesium salt, preferably selected from magnesium oxide, magnesium hydroxide, magnesium citrate, and mixtures thereof. [5] Mass according to any of the preceding claims, wherein the hydrocolloid is selected from pectins, gum arabic, galactomannans, agar, carrageenan, alginates, alginic acids, gelatin, xanthan gum, tragacanth, and mixtures thereof, preferably from pectins and gelatin. [6] Mass according to any of the preceding claims, wherein the water content of the hydrocolloid gel is 1 to 35 wt.%. [7] Mass according to any one of claims 2 to 6, wherein the form of vitamin D is vitamin D3. [8] Mass according to any one of claims 2 to 7, wherein the chromium salt is chromium(III) chloride. [9] Mass according to any of the preceding claims, further comprising vitamin C. [10] Mass according to claim 9, comprising up to 6.0 wt% of vitamin C, based on the total mass of the hydrocolloid gel. [11] Mass according to any one of claims 2 to 10, wherein the form(s) of vitamin D in the hydrocolloid gel are in non-emulsifier-solubulated form. [12] Mass according to any one of claims 2 to 11, wherein at least 50 wt% of the total amount of the at least one form of vitamin D is in non-crystalline form. [13] Mass according to any of the preceding claims for use in the treatment of an existing or imminent deficiency of beneficial active ingredient. [14] Mass for use according to claim 13 in the treatment of an existing or imminent deficiency in a person with diabetes mellitus. [15] Mass for use according to claim 13 in the treatment of an existing or imminent deficiency in a person with autoimmune diseases such as celiac disease.